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EPA-HQ-OPP-2002-0096-0001 | Notice | "2002-06-11T04:00:00" | Norflurazon and Fenbutatin-Oxide Tolerance Reassessment Decisions; Notice of Abailability | [
Federal
Register:
June
11,
2002
(
Volume
67,
Number
112)]
[
Notices]
[
Page
39980
39981]
From
the
Federal
Register
Online
via
GPO
Access
[
wais.
access.
gpo.
gov]
[
DOCID:
fr11jn02
70]
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
2002
0096;
FRL
7181
6]
Norflurazon
and
Fenbutatin
Oxide
Tolerance
Reassessment
Decisions;
Notice
of
Availability
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.
SUMMARY:
This
notice
of
tolerance
reassessment
for
norflurazon
and
fenbutatin
oxide
starts
the
30
day
public
comment
period
during
which
the
public
is
invited
to
submit
comments
on
the
Agency's
Report
of
the
Food
Quality
Protection
Act
(
FQPA)
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
(
TRED)
for
Norflurazon''
and
Report
of
the
Food
Quality
Protection
Act
(
FQPA)
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
(
TRED)
for
Fenbutatin
oxide.''
The
Agency
is
providing
an
opportunity,
through
this
notice,
for
interested
parties
to
comment
on
the
Agency's
tolerance
reassessment
decisions
in
accordance
with
procedures
described
in
Unit
I
of
this
document.
All
comments
will
be
carefully
considered
by
the
Agency.
If
any
comment
causes
the
Agency
to
revise
its
decision
on
tolerance
reassessment
for
norflurazon
and/
or
fenbutatin
oxide,
the
Agency
will
publish
notice
of
its
amendment
in
the
Federal
Register.
DATES:
Comments,
identified
by
docket
ID
number
OPP
2002
0096,
must
be
received
on
or
before
July
11,
2002.
ADDRESSES:
Comments
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
Unit
I
under
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
the
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP
2002
0096
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
Beth
Edwards,
telephone
number:
(
703)
305
5400;
e
mail
address:
edwards.
beth@
epa.
gov
for
norflurazon;
and
Lorilyn
Montford,
telephone
number:
(
703)
308
8170;
e
mail
address:
montford.
lorilyn@
epa.
gov
for
fenbuuutatin
oxide,
Special
Review
and
Reregistration
Division
(
7508C)
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
This
action
is
directed
to
the
public
in
general.
This
action
may,
however,
be
of
interest
to
persons
who
are
or
may
be
required
to
conduct
testing
of
chemical
substances
under
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA)
or
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA);
environmental,
human
health,
and
agricultural
advocates;
pesticides
users;
and
the
public
interested
in
the
use
of
pesticides.
Since
other
entities
may
also
be
interested,
the
Agency
has
not
attempted
to
describe
all
the
specific
entities
that
may
be
affected
by
this
action.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
this
Document
and
Other
Related
Documents?
1.
Electronically.
You
may
obtain
electronic
copies
of
this
document,
and
certain
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
at
http://
www.
epa.
gov/.
To
access
this
document,
on
the
Home
Page
select
Laws
and
Regulations,''
Regulations
and
Proposed
Rules,''
and
then
look
up
the
entry
for
this
document
under
the
Federal
Register
Environmental
Documents.''
You
can
also
go
directly
to
the
Federal
Register
listings
at
http://
www.
epa.
gov/
fedrgstr/.
To
access
TRED
documents
electronically,
go
directly
to
the
TREDs
table
on
the
EPA
Office
of
Pesticide
Programs
Home
Page,
at
http://
www.
epa.
gov/
pesticides/
reregistration/
status.
htm.
2.
In
person.
The
Agency
has
established
an
official
record
for
this
action
under
docket
ID
number
OPP
2002
0096.
The
official
record
consists
of
the
documents
specifically
referenced
in
this
action,
and
other
information
related
to
this
action,
including
any
information
claimed
as
Confidential
Business
Information
(
CBI).
This
official
record
includes
the
documents
that
are
physically
located
in
the
docket,
as
well
as
the
documents
that
are
referenced
in
those
documents.
The
public
version
of
the
official
record
does
not
include
any
information
claimed
as
CBI.
The
public
version
of
the
official
record,
including
printed
and
paper
versions
of
any
electronic
comments
submitted
during
an
applicable
comment
period,
is
available
for
inspection
in
the
Public
Information
and
Records
Integrity
[[
Page
39981]]
Branch
(
PIRIB),
Rm.
119,
Crystal
Mall
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(
703)
305
5805.
C.
How
and
to
Whom
Do
I
Submit
Comments?
You
may
submit
comments
through
the
mail,
in
person,
or
electronically.
To
ensure
proper
receipt
by
the
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP
2002
0096
in
the
subject
line
on
the
first
page
of
your
response.
1.
By
mail.
Submit
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Information
Resources
and
Services
Division
(
7502C),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW,
Washington,
DC
20460.
2.
In
person
or
by
courier.
Deliver
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Information
Resources
and
Services
Division
(
7502C),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
Rm.
119,
Crystal
Mall
2,
1921
Jefferson
Davis
Highway,
Arlington,
VA.
The
PIRIB
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(
703)
305
5805.
3.
Electronically.
You
may
submit
your
comments
electronically
by
e
mail
to:
opp
docket@
epa.
gov,
or
you
can
submit
a
computer
disk
as
described
above.
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
Avoid
the
use
of
special
characters
and
any
form
of
encryption.
Electronic
submissions
will
be
accepted
in
WordPerfect
6.1/
8.0/
9.0
or
ASCII
file
format.
All
comments
in
electronic
form
must
be
identified
by
docket
ID
number
OPP
2002
0096.
Electronic
comments
may
also
be
filed
online
at
many
Federal
Depository
Libraries.
D.
How
Should
I
Handle
CBI
That
I
Want
to
Submit
to
the
Agency?
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
You
may
claim
information
that
you
submit
to
EPA
in
response
to
this
document
as
CBI
by
marking
any
part
or
all
of
that
information
as
CBI.
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
as
CBI
must
be
submitted
for
inclusion
in
the
public
version
of
the
official
record.
Information
not
marked
confidential
will
be
included
in
the
public
version
of
the
official
record
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
CBI,
please
consult
the
appropriate
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?
You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
1.
Explain
your
views
as
clearly
as
possible.
2.
Describe
any
assumptions
that
you
used.
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
your
views.
4.
If
you
estimate
potential
burdens
or
costs,
explain
how
you
arrived
at
the
estimate
that
you
provide.
5.
Provide
specific
examples
to
illustrate
your
concerns.
6.
Offer
alternative
ways
to
improve
the
notice
or
collection
activity.
7.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
document.
8.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
ID
number
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
may
also
provide
the
name,
date,
and
Federal
Register
citation.
II.
Background
A.
What
Action
is
the
Agency
Taking?
This
notice
constitutes
and
announces
the
availability
of
the
norflurazon
and
fenbutatin
oxide
TREDs.
These
decisions
have
been
developed
as
part
of
the
public
participation
process
that
EPA
and
the
U.
S.
Department
of
Agriculture
(
USDA)
are
using
to
involve
the
public
in
the
reassessment
of
pesticide
tolerances
under
FFDCA.
The
EPA
must
review
tolerances
and
tolerance
exemptions
that
were
in
effect
when
FQPA
was
enacted
in
August
1996,
to
ensure
that
these
existing
pesticide
residue
limits
for
food
and
feed
commodities
meet
the
safety
standard
of
the
new
law.
In
reviewing
these
tolerances,
the
Agency
must
consider,
among
other
things,
aggregate
risks
from
non
occupational
sources
of
pesticide
exposure,
whether
there
is
increased
susceptibility
to
infants
and
children,
and
the
cumulative
effects
of
pesticides
with
a
common
mechanism
of
toxicity.
The
tolerances
are
considered
reassessed
once
the
safety
finding
has
been
made
that
aggregate
risks
are
not
of
concern.
A
reregistration
eligibility
decision
(
RED)
was
completed
for
norflurazon
in
June
1996
and
fenbutatin
oxide
in
September
1994,
prior
to
FQPA
enactment,
and
therefore
needed
an
updated
assessment
to
consider
the
provisions
of
the
Act.
FFDCA
requires
that
the
Agency,
when
considering
whether
to
establish,
modify,
or
revoke
a
tolerance,
consider
available
information''
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
other
substances
that
have
a
common
mechanism
of
toxicity.''
At
this
time,
norflurazon
and
fenbutatin
oxide
have
not
been
identified
as
sharing
a
common
mechanism
of
toxicity
and
are
not
scheduled
for
a
cumulative
risk
assessment.
Additionally,
the
tolerances
for
norflurazon
(
58)
and
fenbutatin
oxide
(
42)
are
now
considered
reassessed
as
safe
under
section
408(
q)
of
FFDCA.
The
reregistration
program
is
being
conducted
under
Congressionally
mandated
time
frames,
and
the
EPA
recognizes
both
the
need
to
make
timely
reregistration
decisions
and
to
involve
the
public.
Therefore,
the
Agency
is
issuing
these
TREDs
as
final
documents
because
no
risk
mitigation
or
changes
to
existing
labeling
are
necessary.
All
comments
received
within
30
days
of
publication
of
this
Federal
Register
notice
will
be
carefully
considered
by
the
Agency.
If
any
comment
significantly
impacts
a
TRED,
the
Agency
will
amend
its
decision
by
publishing
a
Federal
Register
notice.
B.
What
is
the
Agency's
Authority
for
Taking
this
Action?
The
legal
authority
for
these
TREDs
falls
under
FIFRA,
as
amended
in
1988
and
1996.
Section
4(
g)(
2)(
A)
of
FIFRA
directs
that,
after
submission
of
all
data
concerning
a
pesticide
active
ingredient,
the
Administrator
shall
determine
whether
pesticides
containing
such
active
ingredient
are
eligible
for
reregistration,''
and
either
reregistering
products
or
taking
other
appropriate
regulatory
action.''
List
of
Subjects
Environmental
protection,
Pesticide
Tolerances.
Dated:
May
31,
2002.
Lois
A
Rossi,
Director,
Special
Review
and
Reregistration
Division,
Office
of
Pesticide
Programs.
[
FR
Doc.
02
14636
Filed
6
10
02;
8:
45
am]
BILLING
CODE
6560
50
S
| epa | 2024-06-07T20:31:42.054013 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0096-0001/content.txt"
} |
EPA-HQ-OPP-2002-0104-0001 | Notice | "2002-06-11T04:00:00" | Industrial Economics Inc.; Transfer of Data | 39978
Federal
Register
/
Vol.
67,
No.
112
/
Tuesday,
June
11,
2002
/
Notices
involving
rates
or
services
applicable
to
public
property.
Small
Business
Regulatory
Enforcement
Fairness
Act
Western
has
determined
that
this
rule
is
exempt
from
Congressional
notification
requirements
under
5
U.
S.
C.
801
because
the
action
is
a
rulemaking
of
particular
applicability
relating
to
rates
or
services
and
involves
matters
of
procedure.
Availability
of
Information
Comments,
letters,
memorandums,
or
other
documents
made
or
kept
by
Western
in
developing
the
proposed
rate
will
be
made
available
for
inspection
and
copying
at
the
Rocky
Mountain
Customer
Service
Region
located
at
5555
East
Crossroads
Boulevard,
Loveland,
CO
80538
8986.
Submission
to
the
Federal
Energy
Regulatory
Commission
The
interim
rate
herein
confirmed,
approved,
and
placed
into
effect,
together
with
supporting
documents,
will
be
submitted
to
FERC
for
confirmation
and
final
approval.
Order
I
confirm
and
approve
on
an
interim
basis,
effective
July
1,
2002,
Rate
Schedule
L
AS4
for
Energy
Imbalance
Service
for
the
Western
Area
Colorado
Missouri
control
area
for
the
Western
Area
Power
Administration.
The
rate
schedule
shall
remain
in
effect
on
an
interim
basis,
pending
FERC
confirmation
and
approval
of
it
or
a
substitute
rate
on
a
final
basis
through
March
31,
2003.
Dated:
May
30,
2002.
Spencer
Abraham,
Secretary.
Rate
Schedule
L
AS4,
(
Supersedes
L
T3);
Schedule
4
to
OATT,
July
1,
2002.
Department
of
Energy
Western
Area
Power
Administration,
Rocky
Mountain
Region,
Western
Area
Colorado
Missouri
Control
Area;
Schedule
of
Rate
for
Energy
Imbalance
Service
Effective
The
first
day
of
the
first
full
billing
period
beginning
on
or
after
July
1,
2002,
through
March
31,
2003.
Available
Within
the
Rocky
Mountain
Customer
Service
Region's
Western
Area
Colorado
Missouri
control
area
(
WACM).
Applicable
To
customers
receiving
Energy
Imbalance
Service
from
WACM.
Character
and
Conditions
of
Service
WACM
provides
Energy
Imbalance
Service
when
there
is
a
difference
between
a
customer's
resources
and
obligations.
Energy
Imbalance
is
calculated
as
resources
minus
obligations
(
adjusted
for
transmission
and
transformer
losses)
for
any
combination
of
scheduled
transfers,
transactions,
or
actual
load
integrated
over
each
hour.
Both
Federal
transmission
customers
and
customers
on
others'
transmission
systems
within
WACM
must
either
obtain
this
service
from
WACM
or
make
alternative
comparable
arrangements
to
satisfy
its
Energy
Imbalance
Service
obligation.
Formula
Rate
All
Energy
Imbalance
Service
provided,
both
inside
and
outside
the
bandwidth,
will
be
settled
financially,
accounted
for
hourly
at
the
end
of
each
month.
The
WACM
shall
establish
a
deviation
band
of
±
5
percent
(
with
a
minimum
of
2
MW)
of
the
actual
load
to
be
applied
hourly
to
any
energy
imbalance
that
occurs
as
a
result
of
a
customer's
schedules
and/
or
meter
data.
Normally,
there
are
four
scenarios
for
Energy
Imbalance
Service,
each
of
which
receive
a
specific
pricing
calculation.
They
are:
(
1)
Over
delivery
within
the
bandwidth;
(
2)
under
delivery
within
the
bandwidth;
(
3)
over
delivery
outside
the
bandwidth;
and
(
4)
under
delivery
outside
the
bandwidth.
During
periods
of
control
area
operating
constraints,
Western
reserves
the
right
to
eliminate
credits
for
over
deliveries
and
parties
over
delivering
may
share
in
the
cost
to
Western
of
the
penalty.
Within
the
Bandwidth
The
gross
energy
imbalance
for
each
applicable
entity
within
WACM
shall
be
totaled
and
netted
to
determine
an
aggregate
energy
imbalance
for
WACM.
The
sign
of
the
aggregate
energy
imbalance
will
determine
whether
sale
or
purchase
pricing
will
be
used
(
surplus
conditions
use
sale
pricing
and
deficit
conditions
will
use
purchase
pricing).
Depending
upon
the
sign
of
the
aggregate
energy
imbalance
for
all
entities
within
WACM,
the
pricing
for
charges
and
credits
within
the
bandwidth
will
be:
Weighted
Average
Sale
or
Purchase
Price
@
100%.
Outside
the
Bandwidth
Each
entity
within
WACM
will
be
charged
or
credited
independently
for
Energy
Imbalance
Service
taken,
dependent
upon
their
over
or
underdelivery
status.
Under
Delivery
(
customer
deficit)
=
Customer
will
be
charged
150%
of
the
weighted
average
real
time
purchase
price.
Over
Delivery
(
customer
surplus)
=
Customer
will
be
credited
50%
of
the
weighted
average
real
time
sale
price.
Expansion
of
the
bandwidth
will
be
allowed
during
the
following
instances:
The
loss
of
a
physical
resource.
Upon
evidence
of
proven
frequency
bias
contribution
for
control
area
needs.
The
transition
(
start
up/
shut
down)
period
for
large
thermal
resources.
Pricing
Defaults
When
no
hourly
data
is
available,
the
pricing
defaults
for
sales
and
purchase
pricing
both
within
and
outside
the
bandwidth
will
be
applied
in
the
following
order:
Weighted
average
real
time
sale
or
purchase
pricing
for
the
day
(
on
and
off
peak).
Weighted
average
real
time
sale
or
purchase
pricing
for
the
month
(
on
and
off
peak).
Weighted
average
real
time
sale
or
purchase
pricing
for
the
prior
month
(
on
and
off
peak).
Weighted
average
real
time
sale
or
purchase
pricing
for
the
month
prior
to
the
prior
month
(
and
continuing
until
sale
or
purchase
pricing
located)
(
on
and
off
peak).
Billing
The
billing
determinants
for
the
above
formula
rates
are
specified
in
the
final
rate
order
and
in
the
associated
service
agreement.
[
FR
Doc.
02
14609
Filed
6
10
02;
8:
45
am]
BILLING
CODE
6450
01
P
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
2002
0104;
FRL
7182
7]
Industrial
Economics
Inc.;
Transfer
of
Data
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.
SUMMARY:
This
notice
announces
that
pesticide
related
information
submitted
to
EPA's
Office
of
Pesticide
Programs
(
OPP)
pursuant
to
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA)
and
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
including
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00000
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39979
Federal
Register
/
Vol.
67,
No.
112
/
Tuesday,
June
11,
2002
/
Notices
information
that
may
have
been
claimed
as
Confidential
Business
Information
(
CBI)
by
the
submitter,
will
be
transferred
to
Industrial
Economics
Inc.
in
accordance
with
40
CFR
2.307(
h)(
3)
and
2.308(
i)(
2).
Industrial
Economics
Inc.
has
been
awarded
multiple
contracts
to
perform
work
for
OPP,
and
access
to
this
information
will
enable
Industrial
Economics
Inc.
to
fulfill
the
obligations
of
the
contract.
DATES:
Industrial
Economics
Inc.
will
be
given
access
to
this
information
on
or
before
June
17,
2002.
FOR
FURTHER
INFORMATION
CONTACT:
By
mail:
Erik
R.
Johnson,
FIFRA
Security
Officer,
Information
Resources
and
Services
Division
(
7502C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(
703)
305
7248;
email
address:
johnson.
erik@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
This
action
applies
to
the
public
in
general.
As
such,
the
Agency
has
not
attempted
to
describe
all
the
specific
entities
that
may
be
affected
by
this
action.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
this
Document
and
Other
Related
Documents?
You
may
obtain
electronic
copies
of
this
document,
and
certain
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
at
http://
www.
epa.
gov/.
To
access
this
document,
on
the
Home
Page
select
``
Laws
and
Regulations,''
``
Regulations
and
Proposed
Rules,''
and
then
look
up
the
entry
for
this
document
under
the
``
Federal
Register
Environmental
Documents.''
You
can
also
go
directly
to
the
Federal
Register
listings
at
http://
www.
epa.
gov/
fedrgstr/.
II.
Contractor
Requirements
Under
contract
number
GS
10F
0224J,
the
contractor
will
perform
the
following:
EPA's
Office
of
Enforcement
and
Compliance
Assurance
(
OECA)
is
responsible
for
providing
assistance
to
enforcement
professionals
from
EPA
and
the
States
in
determining:
(
1)
A
violator's
economic
benefit
of
noncompliance;
(
2)
the
violator's
ability
to
pay
for
compliance,
clean
ups
and
civil
penalties
(
hereinafter
referred
to
as
``
ability
to
pay'');
(
3)
the
value
of
a
supplemental
environmental
project
(
SEP);
and
(
4)
the
value
of
compliance.
This
assistance
is
largely
provided
through
five
current
computer
models:
Ben,
Abel,
Indipay,
Munipay
and
Project.
Ben
calculates
a
violator's
economic
savings
from
violating
the
law.
Abel,
Indipay,
and
Munipay
evaluate
claims
of
inability
to
pay
from
for
profit
entities,
individuals
and
municipalities,
respectively.
Project
calculates
the
net
present,
after
tax
value
of
a
proposed
supplemental
environmental
project.
OECA
also
provides
support
in
these
areas
through
the
use
of
expert
financial
consultants
where
the
models
are
insufficient.
OECA
must
keep
its
models
up
to
date,
provide
educational
programs
to
ensure
proper
application
of
the
models,
support
negotiations,
trials
and
hearings,
and
provide
advice
to
our
enforcement
professionals
as
to
issues
that
arise
in
using
the
models.
Since
there
are
very
few
corporate
finance,
municipal
finance,
or
accounting
experts
within
OECA,
the
contractor
shall
provide
that
expertise
and
update
the
models,
develop
new
models
as
appropriate
and
educate
enforcement
staff
on
the
models.
The
contractor
shall
also
provide
expert
advice
to
enforcement
personnel
regarding
financial
issues
that
impact
enforcement
litigation,
and
when
directed,
support
enforcement
negotiations,
and
appear
as
expert
witnesses
in
hearings
and
trials.
However,
EPA
employees
will
make
all
policy
decisions
in
regard
to
finance/
accounting
issues.
To
the
extent
that
the
work
under
this
contract
requires
access
to
proprietary
or
confidential
business
or
financial
data
of
other
companies,
and
as
long
as,
such
data
remains
proprietary
or
confidential,
the
contractor
shall
protect
such
data
from
unauthorized
use
and
disclosure.
All
files
or
other
information
identified
as
CBI
shall
be
treated
as
confidential
and
kept
in
a
secure
area
with
access
limited
to
only
contractor
personnel
directly
involved
in
the
case
or
special
project
assignment.
The
contractor,
subcontractor,
and
consultant
personnel
are
bound
by
the
requirements
and
sanctions
contained
in
their
contracts
with
EPA
and
in
EPA's
confidentiality
regulations
found
at
40
CFR
part
2,
subpart
B.
The
contractor,
subcontractors,
and
consultant
must
adhere
to
EPAapproved
security
plans
which
describe
procedures
to
protect
CBI,
and
are
required
to
sign
non
disclosure
agreements
before
gaining
access
to
CBI.
All
official
data,
findings,
and
results
of
investigations
and
studies
completed
by
the
contractor
shall
be
available
for
EPA
and
Department
of
Justice
internal
use
only.
The
contractor
shall
not
release
any
part
of
such
data
without
the
written
direction
of
the
project
officer.
This
contract
involves
no
subcontractors.
OPP
has
determined
that
the
contracts
described
in
this
document
involve
work
that
is
being
conducted
in
connection
with
FIFRA,
in
that
pesticide
chemicals
will
be
the
subject
of
certain
evaluations
to
be
made
under
this
contract.
These
evaluations
may
be
used
in
subsequent
regulatory
decisions
under
FIFRA.
Some
of
this
information
may
be
entitled
to
confidential
treatment.
The
information
has
been
submitted
to
EPA
under
sections
3,
4,
6,
and
7
of
FIFRA
and
under
sections
408
and
409
of
FFDCA.
In
accordance
with
the
requirements
of
40
CFR
2.307(
h)(
3),
the
contract
with
Industrial
Economics
Inc.,
prohibits
use
of
the
information
for
any
purpose
not
specified
in
these
contracts;
prohibits
disclosure
of
the
information
to
a
third
party
without
prior
written
approval
from
the
Agency;
and
requires
that
each
official
and
employee
of
the
contractor
sign
an
agreement
to
protect
the
information
from
unauthorized
release
and
to
handle
it
in
accordance
with
the
FIFRA
Information
Security
Manual.
In
addition,
Industrial
Economics
Inc.
is
required
to
submit
for
EPA
approval
a
security
plan
under
which
any
CBI
will
be
secured
and
protected
against
unauthorized
release
or
compromise.
No
information
will
be
provided
to
Industrial
Economics
Inc.
until
the
requirements
in
this
document
have
been
fully
satisfied.
Records
of
information
provided
to
Industrial
Economics
Inc.
will
be
maintained
by
EPA
Project
Officers
for
these
contracts.
All
information
supplied
to
Industrial
Economics
Inc.
by
EPA
for
use
in
connection
with
these
contracts
will
be
returned
to
EPA
when
Industrial
Economics
Inc.
has
completed
its
work.
List
of
Subjects
Environmental
protection,
Business
and
industry,
Government
contracts,
Government
property,
Security
measures.
Dated:
June
3,
2002.
Linda
Vlier
Moos,
Acting
Director,
Information
Resources
and
Services
Division,
Office
of
Pesticide
Programs.
[
FR
Doc.
02
14635
Filed
6
10
02;
8:
45
am]
BILLING
CODE
6560
50
S
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| epa | 2024-06-07T20:31:42.058615 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0104-0001/content.txt"
} |
EPA-HQ-OPP-2002-0108-0001 | Notice | "2002-06-26T04:00:00" | Pesticide Products; Registration Applications.
| 43114
Federal
Register
/
Vol.
67,
No.
123
/
Wednesday,
June
26,
2002
/
Notices
ENVIRONMENTAL
PROTECTION
AGENCY
[
FRL
7237
9]
Request
for
Nominations
to
the
National
and
Governmental
Advisory
Committees
to
the
U.
S.
Representative
to
the
North
American
Commission
for
Environmental
Cooperation
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice
of
request
for
nominations.
SUMMARY:
The
U.
S.
Environmental
Protection
Agency
(
EPA)
is
inviting
nominations
of
qualified
candidates
to
be
considered
for
appointment
to
fill
vacancies
on
the
National
and
Governmental
Advisory
Committees
to
the
U.
S.
Representative
to
the
North
American
Commission
for
Environmental
Cooperation.
Current
vacancies
on
these
committees
are
scheduled
to
be
filled
by
October
1,
2002.
ADDRESSES:
Submit
nominations
to:
Mark
Joyce,
Designated
Federal
Officer,
Office
of
Cooperative
Environmental
Management,
U.
S.
Environmental
Protection
Agency
(
1601A),
1200
Pennsylvania
Avenue
NW.,
Washington,
DC
20004.
FOR
FURTHER
INFORMATION
CONTACT:
Mark
Joyce,
Designated
Federal
Officer,
U.
S.
Environmental
Protection
Agency
(
1601A),
1200
Pennsylvania
Avenue
NW.,
Washington,
DC
20004;
telephone
202
564
9802;
fax
202
501
0661;
email
joyce.
mark@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
The
National
and
Governmental
Advisory
Committees
advise
the
Administrator
of
the
EPA
in
the
Administrator's
capacity
as
the
U.
S.
Representative
to
the
Council
of
the
North
American
Commission
for
Environmental
Cooperation
(
CEC).
The
Committees
are
authorized
under
Articles
17
and
18
of
the
North
American
Agreement
on
Environmental
Cooperation
(
NAAEC),
North
American
Free
Trade
Agreement
(
NAFTA)
Implementation
Act,
P.
L.
103
182
and
as
directed
by
Executive
Order
12915,
entitled
``
Federal
Implementation
of
the
North
American
Agreement
on
Environmental
Cooperation.''
The
Committees
are
responsible
for
providing
advice
to
the
United
States
Representative
on
a
wide
range
of
strategic,
scientific,
technological,
regulatory
and
economic
issues
related
to
implementation
and
further
elaboration
of
the
NAAEC.
The
National
Advisory
Committee
consists
of
12
representatives
of
environmental
groups
and
non
profit
entities,
business
and
industry,
and
educational
institutions.
The
Governmental
Advisory
Committee
consists
of
12
representatives
from
state,
local
and
tribal
governments.
Members
are
appointed
by
the
Administrator
of
EPA
for
a
two
year
term
with
the
possibility
of
reappointment.
The
Committees
usually
meet
3
times
annually
and
the
average
workload
for
Committee
members
is
approximately
10
to
15
hours
per
month.
Members
serve
on
the
Committees
in
a
voluntary
capacity,
but
EPA
does
provide
reimbursement
for
travel
expenses
associated
with
official
government
business.
The
following
criteria
will
be
used
to
evaluate
nominees:
They
have
extensive
professional
knowledge
of
the
subjects
the
Committees
examine,
including
trade
and
the
environment,
the
NAFTA,
the
NAAEC,
and
the
CEC.
They
represent
a
sector
or
group
that
is
involved
in
the
issues
the
Committees
evaluate.
They
have
senior
level
experience
that
will
fill
a
need
on
the
Committees
for
their
particular
expertise.
They
have
a
demonstrated
ability
to
work
in
a
consensus
building
process
with
a
wide
range
of
representatives
from
diverse
constituencies.
Nominees
will
also
be
considered
with
regard
to
the
mandates
of
the
Federal
Advisory
Committee
Act
that
require
the
Committees
to
maintain
diversity
across
a
broad
range
of
constituencies,
sectors,
and
groups.
Nominations
for
membership
must
include
a
resume
describing
the
professional
and
educational
qualifications
of
the
nominee
and
the
nominee's
current
business
address
and
daytime
telephone
number.
Dated:
June
12,
2002.
Mark
N.
Joyce,
Designated
Federal
Officer.
[
FR
Doc.
02
16141
Filed
6
25
02;
8:
45
am]
BILLING
CODE
6560
50
P
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
2002
0108;
FRL
7182
9]
Pesticide
Products;
Registration
Applications
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.
SUMMARY:
This
notice
announces
receipt
of
an
application
to
register
a
pesticide
product
containing
a
new
active
ingredient
not
included
in
any
previously
registered
products
pursuant
to
the
provisions
of
section
3(
c)(
4)
of
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA),
as
amended.
DATES:
Written
comments,
identified
by
the
docket
ID
number
OPP
2002
0108,
must
be
received
on
or
before
July
26,
2002.
ADDRESSES:
Comments
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP
2002
0108
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
By
Mail:
Regulatory
Action
Leader,
Susanne
Cerrelli,
Biopesticides
and
Pollution
Prevention
Division
(
7511C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(
703)
308
8077
and
e
mail
address:
cerrelli.
susanne@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
You
may
be
affected
by
this
action
if
you
are
an
agricultural
producer,
food
manufacturer,
or
pesticide
manufacturer.
Potentially
affected
categories
and
entities
may
include,
but
are
not
limited
to:
Categories
NAICS
codes
Examples
of
potentially
affected
entities
Industry
111
Crop
production
112
Animal
production
311
Food
manufacturing
32532
Pesticide
manufacturing
This
listing
is
not
intended
to
be
exhaustive,
but
rather
provides
a
guide
for
readers
regarding
entities
likely
to
be
affected
by
this
action.
Other
types
of
entities
not
listed
in
the
table
could
also
be
affected.
The
North
American
Industrial
Classification
System
(
NAICS)
codes
have
been
provided
to
assist
you
and
others
in
determining
whether
or
not
this
action
might
apply
to
certain
entities.
If
you
have
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
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Federal
Register
/
Vol.
67,
No.
123
/
Wednesday,
June
26,
2002
/
Notices
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
this
Document
and
Other
Related
Documents?
1.
Electronically.
You
may
obtain
electronic
copies
of
this
document,
and
certain
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
at
http://
www.
epa.
gov/.
To
access
this
document,
on
the
Home
Page
select
``
Laws
and
Regulations,''
``
Regulations
and
Proposed
Rules,''
and
then
look
up
the
entry
for
this
document
under
the
``
Federal
Register
Environmental
Documents.''
You
can
also
go
directly
to
the
Federal
Register
listings
at
http://
www.
epa.
gov/
fedrgstr/.
2.
In
person.
The
Agency
has
established
an
official
record
for
this
action
under
docket
ID
number
OPP
2002
0108.
The
official
record
consists
of
the
documents
specifically
referenced
in
this
action,
any
public
comments
received
during
an
applicable
comment
period,
and
other
information
related
to
this
action,
including
any
information
claimed
as
confidential
business
information
(
CBI).
This
official
record
includes
the
documents
that
are
physically
located
in
the
docket,
as
well
as
the
documents
that
are
referenced
in
those
documents.
The
public
version
of
the
official
record
does
not
include
any
information
claimed
as
CBI.
The
public
version
of
the
official
record,
which
includes
printed,
paper
versions
of
any
electronic
comments
submitted
during
an
applicable
comment
period,
is
available
for
inspection
in
the
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(
703)
305
5805.
C.
How
and
to
Whom
Do
I
Submit
Comments?
You
may
submit
comments
through
the
mail,
in
person,
or
electronically.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP
2002
0108
in
the
subject
line
on
the
first
page
of
your
response.
1.
By
mail.
Submit
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Information
Resources
and
Services
Division
(
7502C),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460.
2.
In
person
or
by
courier.
Deliver
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Information
Resources
and
Services
Division
(
7502C),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Highway,
Arlington,
VA.
The
PIRIB
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(
703)
305
5805.
3.
Electronically.
You
may
submit
your
comments
electronically
by
e
mail
to:
opp
docket@
epa.
gov,
or
you
can
submit
a
computer
disk
as
described
above.
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
Avoid
the
use
of
special
characters
and
any
form
of
encryption.
Electronic
submissions
will
be
accepted
in
WordPerfect
6.1/
8.0
or
ASCII
file
format.
All
comments
in
electronic
form
must
be
identified
by
docket
ID
number
OPP
2002
0108.
Electronic
comments
may
also
be
filed
online
at
many
Federal
Depository
Libraries.
D.
How
Should
I
Handle
CBI
that
I
Want
to
Submit
to
the
Agency?
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
You
may
claim
information
that
you
submit
to
EPA
in
response
to
this
document
as
CBI
by
marking
any
part
or
all
of
that
information
as
CBI.
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
as
CBI
must
be
submitted
for
inclusion
in
the
public
version
of
the
official
record.
Information
not
marked
confidential
will
be
included
in
the
public
version
of
the
official
record
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
CBI,
please
consult
the
person
identified
under
FOR
FURTHER
INFORMATION
CONTACT.
E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?
You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
1.
Explain
your
views
as
clearly
as
possible.
2.
Describe
any
assumptions
that
you
used.
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
your
views.
4.
If
you
estimate
potential
burden
or
costs,
explain
how
you
arrived
at
the
estimate
that
you
provide.
5.
Provide
specific
examples
to
illustrate
your
concerns.
6.
Offer
alternative
ways
to
improve
the
registration
activity.
7.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
notice.
8.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
control
number
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
may
also
provide
the
name,
date,
and
Federal
Register
citation.
II.
Registration
Application
EPA
received
an
application
as
follows
to
register
a
pesticide
product
containing
an
active
ingredient
not
included
in
any
previously
registered
products
pursuant
to
the
provision
of
section
3(
c)(
4)
of
FIFRA.
Notice
of
receipt
of
this
application
does
not
imply
a
decision
by
the
Agency
on
the
application.
Product
Containing
an
Active
Ingredient
not
Included
in
any
Previously
Registered
Product
File
Symbol:
70127
E.
Applicant:
Novozymes
Biologicals,
Inc.,
111
Kelser
Mill
Road,
Salem,
VA
24153.
Product
name:
Novozymes
Biofungicide
Green
ReleafTM
710
140.
Active
ingredient:
Bacillus
licheniformis
Strain
SB3086
at
0.14%.
Proposed
classification/
Use:
None.
A
biological
fungicide
for
use
on
ornamental
turf,
lawns,
golf
courses,
turf
farms
and
ornamental
plants
as
a
preventive
or
curative
treatment
for
several
fungal
diseases.
List
of
Subjects
Environmental
protection,
Pesticides
and
pest.
Dated:
June
12,
2002.
Janet
L.
Andersen,
Director,
Biopesticides
and
Pollution
Prevention
Division,
Office
of
Pesticide
Programs.
[
FR
Doc.
02
16107
Filed
6
25
02;
8:
45
am]
BILLING
CODE
6560
50
S
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
2002
0102;
FRL
7182
2]
Issuance
of
Experimental
Use
Permits
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.
SUMMARY:
EPA
has
granted
experimental
use
permits
(
EUPs)
to
the
following
pesticide
applicants.
An
EUP
permits
use
of
a
pesticide
for
experimental
or
research
purposes
only
in
accordance
with
the
limitations
in
the
permit.
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| epa | 2024-06-07T20:31:42.064010 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0108-0001/content.txt"
} |
EPA-HQ-OPP-2002-0114-0001 | Notice | "2002-06-10T04:00:00" | Exposure Modeling Work Group; Notice of Public Meeting | 39718
Federal
Register
/
Vol.
67,
No.
111
/
Monday,
June
10,
2002
/
Notices
Application
for
Registration
of
Pesticide
Producing
Establishments
(
EPA
Form
3540
8),
the
Notification
of
Registration
of
Pesticide
Producing
Establishments
(
EPA
Form
3540
8A),
and
the
Pesticides
Report
for
Pesticide
Producing
Establishments
(
EPA
Form
3540
16).
Application
for
Registration
of
Pesticide
Producing
Establishments
information,
collected
on
EPA
Form
3540
8,
is
a
one
time
requirement
for
all
pesticide
producing
establishments.
The
reporting
of
pesticide
production
information
collected
on
the
Pesticides
Report
for
Pesticide
Producing
Establishments,
EPA
Form
3540
16,
is
required
within
30
days
of
receipt
of
the
Notification
of
Registration
of
Pesticide
Producing
Establishments
(
EPA
Form
3540
8A);
and
then
annually
thereafter,
on
or
before
March
1.
The
information
is
entered
and
stored
in
EPA's
Office
of
Enforcement
and
Compliance
Assurance
(
OECA)/
Office
of
Compliance
(
OC)
Section
Seven
Tracking
System
(
SSTS),
a
computerized
data
processing
and
record
keeping
system.
The
Office
of
Compliance/
OECA
collects
the
establishment
and
pesticide
production
information
for
compliance
oversight
and
risk
assessment.
The
information
is
used
by
EPA
Regional
pesticide
enforcement
and
compliance
staffs,
OECA,
and
the
Office
of
Pesticide
Programs
(
OPP)
within
the
Office
of
Prevention,
Pesticides
and
Toxic
Substances
(
OPPTS),
as
well
as
the
U.
S.
Department
of
Agriculture
(
USDA),
the
Food
and
Drug
Administration
(
FDA),
other
Federal
agencies,
States
under
Cooperative
Enforcement
Agreements,
and
the
public.
An
agency
may
not
conduct
or
sponsor,
and
a
person
is
not
required
to
respond
to,
a
collection
of
information
unless
it
displays
a
currently
valid
OMB
control
number.
The
OMB
control
numbers
for
EPA's
regulations
are
listed
in
40
CFR
part
9
and
48
CFR
chapter
15.
The
Federal
Register
Notice
required
under
5
CFR
1320.8(
d),
soliciting
comments
on
this
collection
of
information
was
published
on
11/
26/
2001
(
66
FR
59017),
and
no
comments
were
received.
Burden
Statement:
The
annual
public
reporting
and
record
keeping
burden
for
this
collection
of
information
is
estimated
to
be
an
average
of
18
minutes
for
a
one
time
response
for
the
Application
for
Registration
of
Pesticide
Producing
Establishments
(
EPA
Form
3540
8),
and
1
hour
and
26
minutes
for
the
annual
yearly
response
for
the
Pesticides
Report
for
Pesticide
Producing
Establishments
(
EPA
Form
3540
16).
There
is
no
public
burden
associated
with
the
Notification
of
Registration
of
Pesticide
Producing
Establishments
(
EPA
Form
3540
8A)
because
EPA
completes
this
form.
Burden
means
the
total
time,
effort,
or
financial
resources
expended
by
persons
to
generate,
maintain,
retain,
or
disclose
or
provide
information
to
or
for
a
Federal
agency.
This
includes
the
time
needed
to
review
instructions;
develop,
acquire,
install,
and
utilize
technology
and
systems
for
the
purposes
of
collecting,
validating,
and
verifying
information,
processing
and
maintaining
information,
and
disclosing
and
providing
information;
adjust
the
existing
ways
to
comply
with
any
previously
applicable
instructions
and
requirements;
train
personnel
to
be
able
to
respond
to
a
collection
of
information;
search
data
sources;
complete
and
review
the
collection
of
information;
and
transmit
or
otherwise
disclose
the
information.
The
burden
associated
with
this
ICR
is
described
below:
Respondents/
Affected
Entities:
Pesticide
producing
establishments.
Estimated
Number
of
Respondents:
12,412.
Frequency
of
Response:
One
time
and
yearly.
Estimated
Total
Annual
Hour
Burden:
17,959
hours.
Estimated
Total
Annualized
Cost
Burden:
$
0.
Send
comments
on
the
Agency's
need
for
this
information,
the
accuracy
of
the
provided
burden
estimates,
and
any
suggested
methods
for
minimizing
respondent
burden,
including
through
the
use
of
automated
collection
techniques
to
the
addresses
listed
above.
Please
refer
to
EPA
ICR
No.
0160.07
and
OMB
Control
No.
2070
0078
in
any
correspondence.
Dated:
May
29,
2002.
Oscar
Morales,
Director,
Collection
Strategies
Division.
[
FR
Doc.
02
14486
Filed
6
7
02;
8:
45
am]
BILLING
CODE
6560
50
U
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
2002
0114;
FRL
7183
4]
Exposure
Modeling
Work
Group;
Notice
of
Public
Meeting
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.
SUMMARY:
The
Exposure
Modeling
Work
Group
(
EMWG)
will
hold
a
1
day
meeting
on
June
18,
2002.
This
notice
announces
the
location
and
time
for
the
meeting
and
sets
forth
the
tentative
agenda
topics.
DATE:
The
meeting
will
be
held
on
June
18,
2002,
from
9
a.
m.
to
3
p.
m.
ADDRESSES:
This
meeting
will
be
held
at
the
George
Washington
Carver
Center,
Room
4223,
5601
Sunnyside
Ave.,
Beltsville,
MD.
FOR
FURTHER
INFORMATION
CONTACT:
James
N.
Carleton,
Environmental
Fate
and
Effects
Division
(
7507C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(
703)
305
5736;
fax
number:
(
703)
308
6309;
e
mail
address:
carleton.
jim@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
This
action
is
directed
to
the
public
in
general.
This
action
may,
however,
be
of
interest
to
Tribes
with
pesticide
programs
or
pesticide
interests.
Since
other
entities
may
also
be
interested,
the
Agency
has
not
attempted
to
describe
all
the
specific
entities
that
may
be
affected
by
this
action.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
this
Document
and
Other
Related
Documents?
1.
Electronically.
You
may
obtain
electronic
copies
of
this
document,
and
certain
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
at
http://
www.
epa.
gov.
To
access
this
document,
on
the
Home
Page
select
``
Laws
and
Regulations,''
``
Regulations
and
Proposed
Rules,''
and
then
look
up
the
entry
for
this
document
under
the
``
Federal
Register
Environmental
Documents.''
You
can
also
go
directly
to
the
Federal
Register
listings
at
http://
www.
epa.
gov/
fedrgstr.
2.
In
person.
The
Agency
has
established
an
official
record
for
this
action
under
docket
ID
number
OPP
2002
0114.
The
official
record
consists
of
the
documents
specifically
referenced
in
this
action,
any
public
comments
received
during
an
applicable
comment
period,
and
other
information
related
to
this
action,
including
any
information
claimed
as
Confidential
Business
Information
(
CBI).
This
official
record
includes
the
documents
that
are
physically
located
in
the
docket,
as
well
as
the
documents
that
are
referenced
in
those
documents.
The
public
version
of
the
official
record
does
not
include
any
information
claimed
as
CBI.
The
public
version
of
the
official
record,
which
VerDate
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39719
Federal
Register
/
Vol.
67,
No.
111
/
Monday,
June
10,
2002
/
Notices
includes
printed,
paper
versions
of
any
electronic
comments
submitted
during
an
applicable
comment
period,
is
available
for
inspection
in
the
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(
703)
305
5805.
II.
Tentative
Agenda:
This
unit
provides
tentative
agenda
topics
for
the
1
day
meeting.
1.
Welcome
and
introductions.
2.
Old
action
items.
3.
Discussion
of
purpose
of
EMWG.
4.
Update
on
screening
concentration
in
ground
water
(
SCI
GROW).
5.
Update
on
basin
scale
modeling.
6.
Fate
database
structure.
7.
Rice
modeling
and
new
Environmental
Fate
Effects
Division
Model.
8.
Update
on
Watershed
Regression
for
Pesticides
(
WARP).
9.
Overview
of
EFED's
procedure
for
developing
new
scenarios.
List
of
Subjects
Environmental
protection,
Pesticides
and
pests.
Dated:
June
5,
2002.
Elizabeth
Leovey,
Acting
Director,
Environmental
Fate
and
Effects
Division,
Office
of
Pesticide
Programs.
[
FR
Doc.
02
14618
Filed
6
6
02;
1:
50
pm]
BILLING
CODE
6560
50
S
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
2002
0109;
FRL
7183
3]
Technical
Briefing
on
the
Draft
Revised
Organophosphate
Pesticide
Cumulative
Risk
Assessment;
Notice
of
Public
Meeting;
Changes
and
Additions
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.
SUMMARY:
EPA
previously
announced
in
the
Federal
Register
of
May
15,
2002
(
67
FR
34707)
(
FRL
6836
3),
a
public
technical
briefing
on
the
revisions
to
the
preliminary
organophosphate
pesticide
cumulative
risk
assessment,
followed
the
next
day
by
a
public
meeting
of
the
CARAT
Workgroup
on
Cumulative
Risk
Assessment/
Public
Participation
Process.
The
location
of
the
CARAT
Cumulative
Risk
Assessment/
Public
Participation
Process
Workgroup
meeting
on
June
19,
2002,
has
been
changed
to
be
the
same
as
that
of
the
technical
briefing.
In
addition,
a
meeting
of
the
CARAT
Workgroup
on
Transition
has
been
added
on
June
20,
2002.
All
three
meetings
will
be
held
in
the
same
location.
DATES:
The
technical
briefing
will
be
held
on
Tuesday,
June
18,
2002,
from
9
a.
m.
to
5
p.
m.
In
addition,
EPA
and
the
U.
S.
Department
of
Agriculture
will
hold
public
meetings
of
two
CARAT
Workgroups:
Cumulative
Risk
Assessment/
Public
Participation
Process
Workgroup
on
Wednesday,
June
19,
2002,
from
9
a.
m.
to
4
p.
m.,
and
the
Workgroup
on
Transition
on
Thursday,
June
20,
2002,
from
1
p.
m.
to
5
p.
m.
ADDRESSES:
The
technical
briefing
and
both
CARAT
Workgroup
meetings
will
be
held
at
the
Holiday
Inn
Select,
480
King
St.,
Old
Town
Alexandria,
VA.
The
telephone
number
for
the
hotel
is
(
703)
549
6080.
The
hotel
is
located
about
10
blocks
from
the
King
Street
Metro
Station.
FOR
FURTHER
INFORMATION
CONTACT:
By
mail:
Karen
Angulo,
Special
Review
and
Registration
Division
(
7508C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
703
308
8004;
email
address:
angulo.
karen@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
This
action
applies
to
the
public
in
general.
As
such,
the
Agency
has
not
attempted
to
specifically
describe
all
the
entities
potentially
affected
by
this
action.
The
Agency
believes
that
a
wide
range
of
stakeholders
will
be
interested
in
technical
briefings
on
organophosphate
pesticides,
including
environmental,
human
health,
and
agricultural
advocates,
the
chemical
industry,
pesticide
users,
and
members
of
the
public
interested
in
the
use
of
pesticides
on
food.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
this
Document
and
Other
Related
Documents?
1.
Electronically.
You
may
obtain
electronic
copies
of
this
document,
and
certain
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
at
http://
www.
epa.
gov.
To
access
this
document,
on
the
Home
Page
select
``
Laws
and
Regulations,''
``
Regulations
and
Proposed
Rules,''
and
then
look
up
the
entry
for
this
document
under
the
``
Federal
Register
Environmental
Documents.''
You
can
also
go
directly
to
the
Federal
Register
listings
at
http://
www.
epa.
gov/
fedrgstr.
To
access
information
about
organophosphate
pesticides,
you
can
also
go
directly
to
the
Home
Page
for
the
Office
of
Pesticide
Programs
(
OPP)
at
http://
www.
epa.
gov/
pesticides/
op:
In
addition,
information
about
the
cumulative
process
and
the
preliminary
organophosphate
cumulative
risk
assessment
documents
are
found
at
http://
www.
epa.
gov/
pesticides/
cumulative.
2.
In
person.
The
Agency
has
established
an
official
record
under
docket
ID
number
OPP
2002
0109.
The
official
record
consists
of
the
documents
specifically
referenced
in
this
action,
and
other
information
related
to
this
action,
including
any
information
claimed
as
Confidential
Business
Information
(
CBI).
This
official
record
includes
the
documents
that
are
physically
located
in
the
docket,
as
well
as
the
documents
that
are
referenced
in
those
documents.
The
public
version
of
the
official
record
does
not
include
any
information
claimed
as
CBI.
The
public
version
of
the
official
record,
which
includes
printed,
paper
versions
of
any
electronic
comments
submitted
during
an
applicable
comment
period
is
available
for
inspection
in
the
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(
703)
305
5805.
II.
How
Can
I
Request
to
Participate
in
this
Meeting?
This
meeting
is
open
to
the
public.
Outside
statements
by
observers
are
welcome.
Verbal
statements
will
be
limited
to
3
to
5
minutes,
and
it
is
preferred
that
only
one
person
per
organization
present
the
statement.
Any
person
who
wishes
to
file
a
written
statement
may
do
so
immediately
before
or
after
the
meeting.
These
statements
will
become
part
of
the
public
version
of
the
official
record
and
will
be
available
for
public
inspection
at
the
address
listed
in
Unit
I.
List
of
Subjects
Environmental
protection,
Chemicals,
Pesticides
and
pests.
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| epa | 2024-06-07T20:31:42.068608 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0114-0001/content.txt"
} |
EPA-HQ-OPP-2002-0126-0001 | Notice | "2002-11-20T05:00:00" | Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on
Food | 70073
Federal
Register
/
Vol.
67,
No.
224
/
Wednesday,
November
20,
2002
/
Notices
ADDRESSES:
The
meeting
will
be
held
at
Doubletree
Hotel,
300
Army
Navy
Drive,
Arlington,
VA
FOR
FURTHER
INFORMATION
CONTACT:
Georgia
McDuffie,
Field
and
External
Affairs
Division
(
7506c),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
0001;
telephone
number:
(
703)
605
0195;
fax
number:
(
703)
308
1850;
email
address:
mcduffie.
georgia@
epa.
gov.
or
Philip
H.
Gray,
SFIREG
Executive
Secretary,
P.
O.
Box
1249,
Hardwick,
VT
05843
1249;
telephone
number:
(
802)
472
6956;
fax
(
802)
472
6957;
e
mail
address:
aapco@
plainfield.
bypass.
com.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
This
action
is
directed
to
the
public
in
general,
and
may
be
of
particular
interest
to
``
those
persons
who
are
or
may
be
required
to
conduct
testing
of
chemical
substances
under
the
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
or
the
FIFRA''.
Since
other
entities
may
also
be
interested,
the
Agency
has
not
attempted
to
describe
all
the
specific
entities
that
may
be
affected
by
this
action.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
Can
I
Get
Copies
of
this
Document
and
Other
Related
Information?
1.
Docket.
EPA
has
established
an
official
public
docket
for
this
action
under
docket
ID
number
OPP
2002
0306.
The
official
public
docket
consists
of
the
documents
specifically
referenced
in
this
action,
any
public
comments
received,
and
other
information
related
to
this
action.
Although,
a
part
of
the
official
docket,
the
public
docket
does
not
include
Confidential
Business
Information
(
CBI)
or
other
information
whose
disclosure
is
restricted
by
statute.
The
official
public
docket
is
the
collection
of
materials
that
is
available
for
public
viewing
at
the
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA.
This
docket
facility
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
docket
telephone
number
is
(
703)
305
5805.
2.
Electronic
access.
You
may
access
this
Federal
Register
document
electronically
through
the
EPA
Internet
under
the
``
Federal
Register''
listings
at
http://
www.
epa.
gov/
fedrgstr/.
An
electronic
version
of
the
public
docket
is
available
through
EPA's
electronic
public
docket
and
comment
system,
EPA
dockets.
You
may
use
EPA
dockets
at
http://
www.
epa.
gov/
edocket/
to
view
public
comments,
access
the
index
listing
of
the
contents
of
the
official
public
docket,
and
to
access
those
documents
in
the
public
docket
that
are
available
electronically.
Although,
not
all
docket
materials
may
be
available
electronically,
you
may
still
access
any
of
the
publicly
available
docket
materials
through
the
docket
facility
identified
in
Unit
I.
B.
1.
Once
in
the
system,
select
``
search,''
then
key
in
the
appropriate
docket
ID
number.
II.
Tentative
Agenda:
1.
Committee
Business
Issues.
2.
Regional
Reports
&
Introduction
of
Issue
Papers/
Action
Items.
3.
Comments
to
the
Committee/
Open
Discussion
with
EPA
Senior
Managers
(
To
be
determined).
4.
Worker
Protection
Standard
(
WPS)
Program
Element
Review
Update.
5.
Non
English/
Multiple
Language
Labels.
6.
Tribal
Pesticide
Program
Council
(
TPPC)/
Section
18s
&
other
Tribal
Issues.
7.
Update
on
Current
OPP
&
OECA
Activities.
8.
SFIREG
Issue
Paper
Status
Report.
9.
Closed
Session.
10.
Pesticide
Regulatory
Education
Program
(
PREP)
Briefing/
Issues.
11.
Soybean
Rust
Pest/
Section
18s
Requests.
12.
Status
(
SLA)
Label
Improvement
Project
Proposals
i.
e.
Mosquito
Products/
West
Nile
virus
Issues
13.
States
Label
Issue
Tracking
System
(
SLITS)
Update
14.
Certification
Training
Assessment
Group
(
CTAG)
Update
&
Discussion
15.
Issue
Papers/
Past
&
Present
List
of
Subjects
Environmental
protection,
Pesticide
and
pests.
Dated:
November
6,
2002.
Jay
Ellenberger,
Associate
Director,
Field
and
External
Affairs
Division,
Office
of
Pesticide
Programs.
[
FR
Doc.
02
29171
Filed
11
19
02;
8:
45
a.
m.]
BILLING
CODE
6560
50
S
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
2002
0126;
FRL
7184
7]
Notice
of
Filing
a
Pesticide
Petition
to
Establish
a
Tolerance
for
a
Certain
Pesticide
Chemical
in
or
on
Food
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.
SUMMARY:
This
notice
announces
the
initial
filing
of
a
pesticide
petition
proposing
the
establishment
of
regulations
for
residues
of
a
certain
pesticide
chemical
in
or
on
various
food
commodities.
DATES:
Comments,
identified
by
docket
ID
number
OPP
2002
0126,
must
be
received
on
or
before
December
20,
2002.
ADDRESSESS:
Comments
may
be
submitted
electronically,
by
mail,
or
through
hand
delivery/
courier.
Follow
the
detailed
instructions
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP
2002
0126
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
By
mail:
Joanne
I.
Miller,
Registration
Division,
Office
of
Pesticide
Programs,
(
7505C)
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(
703)
305
6224;
e
mail
address:
miller.
joanne@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
You
may
be
affected
by
this
action
if
you
are
an
agricultural
producer,
food
manufacturer,
or
pesticide
manufacturer.
Potentially
affected
categories
and
entities
may
include,
but
are
not
limited
to:
Categories
NAICS
codes
Examples
of
potentially
affected
entities
Industry
111
Crop
productionmption
112
Animal
production
311
Food
manufacturing
32532
Pesticide
manufacturing
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31>
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16:
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Nov
19,
2002
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00000
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70074
Federal
Register
/
Vol.
67,
No.
224
/
Wednesday,
November
20,
2002
/
Notices
This
listing
is
not
intended
to
be
exhaustive,
but
rather
provides
a
guide
for
readers
regarding
entities
likely
to
be
affected
by
this
action.
Other
types
of
entities
not
listed
in
this
unit
could
also
be
affected.
The
North
American
Industrial
Classification
System
(
NAICS)
codes
have
been
provided
to
assist
you
and
others
in
determining
whether
this
action
might
apply
to
certain
entities.
To
determine
whether
you
or
your
business
may
be
affected
by
this
action,
you
should
examine
the
applicability
provisions
in
OPP
2002
0126.
If
you
have
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Copies
of
this
Document
and
Other
Related
Information?
1.
Docket.
EPA
has
established
an
official
public
docket
for
this
action
under
docket
identification
(
ID)
number
OPP
2002
0126.
The
official
public
docket
consists
of
the
documents
specifically
referenced
in
this
action,
any
public
comments
received,
and
other
information
related
to
this
action.
Although
a
part
of
the
official
docket,
the
public
docket
does
not
include
Confidential
Business
Information
(
CBI)
or
other
information
whose
disclosure
is
restricted
by
statute.
The
official
public
docket
is
the
collection
of
materials
that
is
available
for
public
viewing
at
the
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA.
This
docket
facility
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
docket
telephone
number
is
(
703)
305
5805.
2.
Electronic
access.
You
may
access
this
Federal
Register
document
electronically
through
the
EPA
Internet
under
the
``
Federal
Register''
listings
at
http://
www.
epa.
gov/
fedrgstr/.
An
electronic
version
of
the
public
docket
is
available
through
EPA's
electronic
public
docket
and
comment
system,
EPA
Dockets.
You
may
use
EPA
Dockets
at
http://
www.
epa.
gov/
edocket/
to
submit
or
view
public
comments,
access
the
index
listing
of
the
contents
of
the
official
public
docket,
and
to
access
those
documents
in
the
public
docket
that
are
available
electronically.
Once
in
the
system,
select
``
search,''
then
key
in
the
appropriate
docket
ID
number.
Certain
types
of
information
will
not
be
placed
in
the
EPA
Dockets.
Information
claimed
as
CBI
and
other
information
whose
disclosure
is
restricted
by
statute,
which
is
not
included
in
the
official
public
docket,
will
not
be
available
for
public
viewing
in
EPA's
electronic
public
docket.
EPA's
policy
is
that
copyrighted
material
will
not
be
placed
in
EPA's
electronic
public
docket
but
will
be
available
only
in
printed,
paper
form
in
the
official
public
docket.
To
the
extent
feasable,
publicly
available
docket
materials
will
be
made
available
in
EPA's
electronic
public
docket.
When
a
document
is
selected
from
the
index
list
in
EPA
Dockets,
the
system
will
identify
whether
the
document
is
available
for
viewing
in
EPA's
electronic
public
docket.
Although
not
all
docket
materials
may
be
available
electronically,
you
may
still
access
any
of
the
publicly
available
docket
materials
through
the
docket
facility
identified
in
Unit
I.
B.
1.
EPA
intends
to
work
towards
providing
electronic
access
to
all
of
the
publicly
available
docket
materials
through
EPA's
electronic
public
docket.
For
public
commenters,
it
is
important
to
note
that
EPA's
policy
is
that
public
comments,
whether
submitted
electronically
or
in
paper,
will
be
made
available
for
public
viewing
in
EPA's
electronic
public
docket
as
EPA
receives
them
and
without
change,
unless
the
comment
contains
copyrighted
material,
CBI,
or
other
information
whose
disclosure
is
restricted
by
statute.
When
EPA
identifies
a
comment
containing
copyrighted
material,
EPA
will
provide
a
reference
to
that
material
in
the
version
of
the
comment
that
is
placed
in
EPA's
electronic
public
docket.
The
entire
printed
comment,
including
the
copyrighted
material,
will
be
available
in
the
public
docket.
Public
comments
submitted
on
computer
disks
that
are
mailed
or
delivered
to
the
docket
will
be
transferred
to
EPA's
electronic
public
docket.
Public
comments
that
are
mailed
or
delivered
to
the
docket
will
be
scanned
and
placed
in
EPA's
electronic
public
docket.
Where
practical,
physical
objects
will
be
photographed,
and
the
photograph
will
be
placed
in
EPA's
electronic
public
docket
along
with
a
brief
description
written
by
the
docket
staff.
C.
How
and
to
Whom
Do
I
Submit
Comments?
You
may
submit
comments
electronically,
by
mail,
or
through
hand
delivery/
courier.
To
ensure
proper
receipt
by
EPA,
identify
the
appropriate
docket
ID
number
in
the
subject
line
on
the
first
page
of
your
comment.
Please
ensure
that
your
comments
are
submitted
within
the
specified
comment
period.
Comments
received
after
the
close
of
the
comment
period
will
be
marked
``
late.''
EPA
is
not
required
to
consider
these
late
comments.
If
you
wish
to
submit
CBI
or
information
that
is
otherwise
protected
by
statute,
please
follow
the
instructions
in
Unit
I.
D.
Do
not
use
EPA
Dockets
or
e
mail
to
submit
CBI
or
information
protected
by
statute.
1.
Electronically.
If
you
submit
an
electronic
comment
as
prescribed
in
this
unit,
EPA
recommends
that
you
include
your
name,
mailing
address,
and
an
email
address
or
other
contact
information
in
the
body
of
your
comment.
Also
include
this
contact
information
on
the
outside
of
any
disk
or
CD
ROM
you
submit,
and
in
any
cover
letter
accompanying
the
disk
or
CD
ROM.
This
ensures
that
you
can
be
identified
as
the
submitter
of
the
comment
and
allows
EPA
to
contact
you
in
case
EPA
cannot
read
your
comment
due
to
technical
difficulties
or
needs
further
information
on
the
substance
of
your
comment.
EPA's
policy
is
that
EPA
will
not
edit
your
comment,
and
any
indentifying
or
contact
information
provided
in
the
body
of
a
comment
will
be
included
as
part
of
the
comment
that
is
placed
in
the
official
public
docket,
and
made
available
in
EPA's
electronic
public
docket.
If
EPA
cannot
read
your
comment
due
to
technical
difficulties
and
cannot
contact
you
for
clarification,
EPA
may
not
be
able
to
consider
your
comment,
i.
EPA
Dockets.
Your
use
of
EPA's
electronic
public
docket
to
submit
comments
to
EPA
electronically
is
EPA's
preferred
method
for
receiving
comments.
Go
directly
to
EPA
Dockets
at
http://
www.
epa.
gov/
edocket,
and
follow
the
online
instructions
for
submitting
comments.
Once
in
the
system,
select
``
search,''
and
then
key
in
docket
ID
number
OPP
2002
0126.
The
system
is
an
``
anonymous
access''
system,
which
means
EPA
will
not
know
your
identity,
e
mail
address,
or
other
contact
information
unless
you
provide
it
in
the
body
of
your
comment.
ii.
E
mail.
Comments
may
be
sent
by
e
mail
to
opp
docket@
epa.
gov,
Attention:
Docket
ID
Number
OPP
2002
0126.
In
contrast
to
EPA's
electronic
public
docket,
EPA's
email
system
is
not
an
``
anonymous
access''
system.
If
you
send
an
e
mail
comment
directly
to
the
docket
without
going
through
EPA's
electronic
public
docket,
EPA's
e
mail
system
automatically
captures
your
e
mail
address.
E
mail
addresses
that
are
automatically
captured
by
EPA's
e
mail
system
are
included
as
part
of
the
comment
that
is
placed
in
the
official
public
docket,
and
made
available
in
EPA's
electronic
public
docket.
iii.
Disk
or
CD
ROM.
You
may
submit
comments
on
a
disk
or
CD
ROM
that
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Notices
you
mail
to
the
mailing
address
identified
in
Unit
I.
C.
2.
These
electronic
submissions
will
be
accepted
in
WordPerfect
or
ASCII
file
format.
Avoid
the
use
of
special
characters
and
any
form
of
encryption.
2.
By
mail.
Send
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB)
(
7502C),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460
0001,
Attention:
Docket
ID
Number
Opp
2002
0126.
3.
By
hand
delivery
or
courier.
Deliver
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
Attention:
Docket
ID
Number
OPP
2002
0126.
Such
deliveries
are
only
accepted
during
the
docket's
normal
hours
of
operation
as
identified
in
Unit
I.
B.
1.
D.
How
Should
I
Submit
CBI
to
the
Agency?
Do
not
submit
information
that
you
consider
to
be
CBI
electronically
through
EPA's
electronic
public
docket
or
by
e
mail.
You
may
claim
information
that
you
submit
to
EPA
as
CBI
by
marking
any
part
or
all
of
that
information
as
CBI
(
if
you
submit
CBI
on
disk
or
CD
ROM,
mark
the
outside
of
the
disk
or
CD
ROM
as
CBI
and
then
identify
electronically
within
the
disk
or
CD
ROM
the
specific
information
that
is
CBI).
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
as
CBI
must
be
submitted
for
inclusion
in
the
public
docket
and
EPA's
electronic
public
docket.
If
you
submit
the
copy
that
does
not
contain
CBI
on
disk
or
CD
ROM,
mark
the
outside
of
the
disk
or
CD
ROM
ckearly
that
it
does
not
contain
CBI.
Information
not
marked
as
CBI
will
be
included
in
the
public
docket
and
EPA's
electronic
public
docket
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
CBI,
please
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?
You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
1.
Explain
your
views
as
clearly
as
possible.
2.
Describe
any
assumptions
that
you
used.
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
your
views.
4.
If
you
estimate
potential
burden
or
costs,
explain
how
you
arrived
at
the
estimate
that
you
provide.
5.
Provide
specific
examples
to
illustrate
your
concerns.
6.
Offer
alternative
ways
to
improve
the
notice
or
collection
activity.
7.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
document.
8.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
ID
number
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
may
also
provide
the
name,
date,
and
Federal
Register
citation.
II.
What
Action
is
the
Agency
Taking?
EPA
has
received
a
pesticide
petition
as
follows
proposing
the
establishment
and/
or
amendment
of
regulations
for
residues
of
a
certain
pesticide
chemical
in
or
on
various
food
commodities
under
section
408
of
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
21
U.
S.
C.
346a.
EPA
has
determined
that
this
petition
contains
data
or
information
regarding
the
elements
set
forth
in
section
408(
d)(
2);
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
support
granting
of
the
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.
List
of
Subjects
Environmental
protection,
Pesticides
and
pests.
Dated:
October
27,
2002.
Debra
Edwards,
Acting
Director,
Registration
Division,
Office
of
Pesticide
Programs.
Summary
of
Petition
The
petitioner
summary
of
the
pesticide
petition
is
printed
below
as
required
by
section
408(
d)(
3)
of
the
FFDCA.
The
summary
of
the
petition
was
prepared
by
Nichino
America
Incorporated,
and
represents
the
view
of
Nichino
America
Incorporated.
The
petition
summary
announces
the
availability
of
a
description
of
the
analytical
methods
available
to
EPA
for
the
detection
and
measurement
of
the
pesticide
chemical
residues,
or
an
explanation
of
why
no
such
method
is
needed.
Nichino
America
Incorporated
PP
1F6428
EPA
has
received
a
pesticide
petition
(
1F6428)
from
Nichino
America
Incorporated,
4550
New
Linden
Hill
Road,
Suite
501,
Wilmington,
DE
19808
proposing,
pursuant
to
section
408(
d)
of
the
FFDCA,
21
U.
S.
C.
346a(
d),
to
amend
40
CFR
part
180,
by
establishing
a
tolerances
for
combined
residues
of
pyraflufen
ethyl
(
ethyl
2
chloro
5(
4
chloro
5
difluoromethoxy
1
methylpyrazol
3
yl)
4
fluorophenoxyacetate)
and
its
acid
metabolite,
E
1,
(
2
chloro
5(
4
chloro
5
difluoromethoxy
1
methylpyrazol
3
yl)
4
fluorophenoxyacetic
acid)
expressed
as
the
ester
equivalent
in
or
on
the
raw
agricultural
commodities
(
RACs)
derived
from
cotton;
undelinted
seed
at
0.05
parts
per
million
(
ppm);
and
gin
byproducts
at
1.5
ppm;
in
or
on
the
RAC
potato
at
0.02
ppm;
in
or
on
the
RACs
corn
grain,
corn
stover,
corn
forage,
soybean
seed,
soybean
forage,
and
soybean
hay
at
0.01
ppm;
wheat
forage,
wheat
hay,
wheat
straw,
and
wheat
grain
at
0.01
ppm.
EPA
has
determined
that
the
petition
contains
data
or
information
regarding
the
elements
set
forth
in
section
408(
d)(
2)
of
the
FFDCA;
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
support
granting
of
the
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.
A.
Residue
Chemistry
1.
Plant
metabolism.
The
qualitative
nature
of
the
residues
of
pyraflufenethyl
(
ET
751)
in
cotton,
potatoes,
corn,
soybeans,
and
wheat
is
adequately
understood.
The
metabolism
of
pyraflufen
ethyl
has
been
studied
in
cotton,
wheat,
and
potato.
Metabolism
in
the
plant
involves
ester
hydrolysis,
de
methylation
on
the
pyrazole
ring
and
further
degradation
of
the
phenoyxyacetate
moiety
to
bound
polar
metabolites.
The
nature
of
the
residue
is
adequately
understood
and
the
residues
of
concern
are
the
parent,
pyraflufenethyl
and
the
acid
metabolite,
E
1,
only.
2.
Analytical
method.
The
enforcement
analytical
method
utilizes
gas
chromatography/
mass
spectrophotometry
with
selected
ion
monitoring
for
detecting
and
measuring
levels
of
pyraflufen
ethyl
and
the
acid
metabolite
with
a
general
limit
of
quantification
(
LOQ)
of
0.02
ppm
(
combined
E
1
and
parent).
This
method
allows
detection
of
residues
at
or
above
the
proposed
tolerances.
The
method
has
undergone
independent
laboratory
validation
as
required
by
PR
Notices
88
5
and
96
1.
3.
Magnitude
of
residues
in
crops
i.
Potato.
No
apparent
residues
of
pyraflufen
ethyl
were
observed
in
potato
at
or
above
0.02
ppm
(
the
LOQ
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for
the
analytical
method).
The
field
studies,
conducted
at
3x
the
highest
intended
label
use
rate,
in
16
trials
in
11
states,
clearly
support
the
proposed
tolerances
of
0.02
ppm
(
combined
E
1
and
parent).
No
detectable
residues
of
parent
or
the
acid
metabolite
were
observed
in
any
processed
potato
fraction
at
5x
the
maximum
proposed
application
rate
and
proposed
preharvest
interval
(
PHI)
in
a
field
study,
with
the
LOQ
of
0.02
ppm
(
combined
E
1
and
parent).
The
tolerance
that
is
being
proposed
for
the
use
of
pyraflufen
ethyl
plus
the
acid
metabolite
on
potato
is
0.02
ppm.
ii.
Cotton.
Twelve
field
residue
trials
were
conducted
in
seven
different
states.
Applications
in
the
trials
were
3x
the
proposed
label
directions
for
use
and
at
the
proposed
PHI
of
7
days.
Analysis
of
the
treated
samples
showed
that
the
residues
of
pyraflufen
ethyl
(
ethyl
2
chloro
5(
4
chloro
5
difluoromethoxy
1
methylpyrazol
3
yl)
4
fluorophenoxyacetate)
plus
its
acid
metabolite,
E
1,
(
2
chloro
5(
4
chloro
5
difluoromethoxy
1
methylpyrazol
3
yl)
4
fluorophenoxyacetic
acid)
expressed
as
the
ester
equivalent
at
the
exaggerated
rate,
were
below
the
proposed
tolerance
of
0.05
ppm
in
cotton
seed
at
the
proposed
labeled
PHI
in
all
samples.
No
residues
were
seen
in
the
processed
fractions
of
meal,
hull,
and
oil,
when
one
trial
was
run
in
a
typical
cotton
growing
area.
The
application
rate
for
this
processing
study
was
15x
the
maximum
proposed
application
rate
and
at
the
proposed
PHI.
This
indicates
that
there
is
no
concentration
of
pyraflufen
ethyl
(
ethyl
2
chloro
5(
4
chloro
5
difluoromethoxy
1
methylpyrazol
3
yl)
4
fluorophenoxyacetate)
plus
its
acid
metabolite,
E
1,
(
2
chloro
5(
4
chloro
5
difluoromethoxy
1
methylpyrazol
3
yl)
4
fluorophenoxyacetic
acid),
expressed
as
the
ester
equivalent
in
any
of
the
processed
fractions.
Low
residues
seen
in
the
undelinted
cottonseed
were
consistent
with
the
magnitude
of
residue
trials.
Combined
residues
of
pyraflufen
ethyl
(
ethyl
2
chloro
5(
4
chloro
5
difluoromethoxy
1
methylpyrazol
3
yl)
4
fluorophenoxyacetate)
plus
its
acid
metabolite,
E
1
(
2
chloro
5(
4
chloro
5
difluoromethoxy
1
methylpyrazol
3
yl)
4
fluorophenoxyacetic
acid)
in
cotton
gin
byproducts
from
applications
at
3x
the
proposed
application
rate
ranged
from
0.125
ppm
to
1.314
ppm,
and
averaged
0.035
ppm
from
applications
made
at
1x
the
proposed
application
rate.
The
proposed
tolerance
of
0.05
ppm
for
pyraflufen
ethyl
(
ethyl
2
chloro
5(
4
chloro
5
difluoromethoxy
1
methylpyrazol
3
yl)
fluorophenoxyacetate)
plus
its
acid
metabolite,
E
1,
(
2
chloro
5(
4
chloro
5
difluoromethoxy
1
methylpyrazol
3
yl)
4
fluorophenoxyacetic
acid)
in
cotton
seed
and
1.5
ppm
in
cotton
gin
byproducts
are
supported
by
the
field
residue
data.
iii.
Corn.
Three
exaggerated
rate
residue
trials
were
conducted
in
three
different
states
on
different
soil
types.
Applications
in
the
trials
were
5x
to
10x
the
proposed
label
directions
for
use
as
a
pre
plant
burndown
herbicide.
Analysis
of
the
treated
samples
showed
zero
residues
of
pyraflufen
ethyl
(
ethyl
2
chloro
5(
4
chloro
5
difluoromethoxy
1
methylpyrazol
3
yl)
4
fluorophenoxyacetate)
plus
its
acid
metabolite,
E
1,
(
2
chloro
5(
4
chloro
5
difluoromethoxy
1
methylpyrazol
3
yl)
4
fluorophenoxyacetic
acid)
expressed
as
the
ester
equivalent
at
the
exaggerated
rate.
The
LOQ
for
the
parent
and
the
metabolite
was
0.005
ppm
in
each
case.
Since
no
residues
were
observed
at
exaggerated
rates
in
RACs,
no
processing
studies
were
conducted.
iv.
Soybean.
Three
exaggerated
rate
residue
trials
were
conducted
in
three
different
states
on
different
soil
types.
Applications
in
the
trials
were
5x
to
10x
the
proposed
label
directions
for
use
as
a
pre
plant
burndown
herbicide.
Analysis
of
the
treated
samples
showed
zero
residues
of
pyraflufen
ethyl
(
ethyl
2
chloro
5(
4
chloro
5
difluoromethoxy
1
methylpyrazol
3
yl)
4
fluorophenoxyacetate)
plus
its
acid
metabolite,
E
1,
(
2
chloro
5(
4
chloro
5
difluoromethoxy
1
methylpyrazol
3
yl)
4
fluorophenoxyacetic
acid)
expressed
as
the
ester
equivalent
at
the
exaggerated
rate.
The
LOQ
for
the
parent
and
the
metabolite
was
0.005
ppm
in
each
case.
Since
no
residues
were
observed
at
exaggerated
rates
in
RACs,
no
processing
studies
were
conducted.
v.
Wheat.
Three
exaggerated
rate
residue
trials
were
conducted
in
three
different
states
on
different
soil
types.
Applications
in
the
trials
were
5x
to
10x
the
proposed
label
directions
for
use
as
a
pre
plant
burndown
herbicide.
Analysis
of
the
treated
samples
showed
zero
residues
of
pyraflufen
ethyl
(
ethyl
2
chloro
5(
4
chloro
5
difluoromethoxy
1
methylpyrazol
3
yl)
4
fluorophenoxyacetate)
plus
its
acid
metabolite,
E
1,
(
2
chloro
5(
4
chloro
5
difluoromethoxy
1
methylpyrazol
3
yl)
4
fluorophenoxyacetic
acid)
expressed
as
the
ester
equivalent
at
the
exaggerated
rate.
The
LOQ
for
the
parent
and
the
metabolite
was
0.005
ppm
in
each
case.
Since
no
residues
were
observed
at
exaggerated
rates
in
RACs,
no
processing
studies
were
conducted.
4.
Magnitude
of
the
residue
in
animals.
i.
Ruminants.
The
maximum
dietary
burden
in
beef
and
dairy
cows
results
from
a
diet
comprised
of
undelinted
cottonseed,
cotton
meal,
cotton
hulls,
cotton
gin
byproducts,
potato
culls,
potato
waste,
and
from
grain
(
seed),
forage,
hay,
stover
(
fodder),
silage,
meal,
hulls,
straw,
aspirated
grain
fractions,
and
milled
byproducts
of
corn,
soybeans,
and
wheat
for
a
total
dietary
burden
that
is
significantly
lower
than
levels
that
would
require
the
proposal
of
tolerances
in
ruminants.
This
conclusion
is
based
on
exaggerated
rate
animal
metabolism
studies
carried
out
on
pyraflufen
ethyl
and
its
significant
metabolites.
Therefore,
an
exemption
from
tolerances
in
milk,
meat,
and
meat
by
products
under
40
CFR
180.6(
a)(
3)
and
(
b)
is
proposed
as
it
is
not
possible
to
establish
with
certainty
whether
finite
residues
will
be
incurred,
but
there
is
no
reasonable
expectation
of
finite
residues.
ii.
Poultry.
The
maximum
poultry
dietary
burden
results
from
a
diet
comprised
of
cotton
meal,
corn
grain,
corn
milled
byproducts,
soybean
seed,
soybean
meal,
soybean
hulls,
wheat
grain,
and
wheat
milled
byproducts
for
a
total
dietary
burden
that
is
significantly
lower
than
the
levels
that
would
require
the
proposal
of
tolerances
in
poultry.
This
conclusion
is
based
on
the
exaggerated
rate
metabolism
studies
carried
out
on
pyraflufen
ethyl
and
its
acid
metabolite.
Therefore,
an
exemption
from
tolerances
in
poultry
meat,
meat
byproducts,
fat,
and
eggs
under
40
CFR
180.6(
a)(
3)
and
(
b)
is
proposed
as
it
is
not
possible
to
establish
with
certainty
whether
finite
residues
will
be
incurred,
but
there
is
no
reasonable
expectation
of
finite
residues.
B.
Toxicological
Profile
1.
Acute
toxicity.
Pyraflufen
ethyl
technical
is
considered
to
be
nontoxic
(
toxicity
category
IV)
to
the
rat
by
the
oral
route
of
exposure.
In
an
acute
oral
toxicity
study
conducted
in
rats,
the
oral
LD50
value
for
technical
pyraflufen
ethyl
was
determined
to
be
>
5,000
milligrams/
kilograms
body
weight
(
mg/
kg
bwt).
The
results
from
the
acute
dermal
toxicity
study
in
rabbits
indicate
that
pyraflufen
ethyl
is
slightly
toxic
(
toxicity
category
III)
to
rabbits
by
the
dermal
route
of
exposure.
The
dermal
LD50
value
of
technical
pyraflufen
ethyl
was
determined
to
be
>
2,000
mg/
kg
for
both
male
and
female
rabbits.
Pyraflufen
ethyl
technical
is
considered
to
be
nontoxic
(
toxicity
category
IV)
to
the
rat
by
the
respiratory
route
of
exposure.
Inhalation
exposure
of
rats
to
pyraflufen
ethyl
technical
resulted
in
an
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70077
Federal
Register
/
Vol.
67,
No.
224
/
Wednesday,
November
20,
2002
/
Notices
LC50
>
5.53
milligrams/
Liter
(
mg/
L)
(
analytical)
for
both
males
and
females.
Pyraflufen
ethyl
technical
was
shown
to
be
non
irritating
to
rabbit
skin
(
toxicity
category
IV).
Pyraflufen
ethyl
technical
was
shown
to
be
slightly
irritating
to
rabbit
eyes
(
toxicity
category
III).
Application
of
technical
material
to
the
rabbit
eye
resulted
in
iris
and
conjunctival
irritation
from
1
to
24
hours,
which
was
clear
by
72
hours.
Based
on
the
results
of
a
dermal
sensitization
study,
pyraflufen
ethyl
technical
is
not
considered
a
sensitizer
in
guinea
pigs.
2.
Genotoxicity.
Pyraflufen
ethyl
technical
was
not
mutagenic
in
any
of
the
following
genotoxicity
studies.
Point
mutations
in
bacteria
in
an
Ames
study
with
Salmonella
typhimurium,
and
Escherichia
coli;
negative
in
chromosome
aberrations
in
vitro
human
lymphocytes,
and
in
the
mouse
micronucleus;
negative
for
DNA
repair
in
in
vitro
and
in
vivo
rat
liver
hepatocyte
assays
and
Bacillus
subtillis.
For
mammalian
gene
mutation,
in
one
in
vitro
mouse
lymphoma
mutation
assay,
no
evidence
of
mutagenicity
was
seen
in
the
absence
of
metabolic
activation.
With
S9
activation
at
levels
up
to
200
i
g/
Liter,
equivocal
results
were
seen.
The
study
report
provided
no
criteria
for
positive
or
negative
responses.
When
this
in
vitro
study
was
repeated,
no
positive
or
equivocal
results
in
the
presence
of
activation
with
S9
at
levels
of
S9
up
to
350
i
g/
Liter
were
seen.
These
levels
of
activation
were
greater
than
those
tested
in
the
earlier
study
and
both
small
and
large
colonies
were
counted.
The
overall
weight
of
evidence
indicates
that
pyraflufen
ethyl
is
not
genotoxic.
3.
Reproductive
and
developmental
toxicity.
The
developmental
toxicity
study
in
rats
conducted
with
pyraflufenethyl
technical
showed
no
evidence
of
teratogenic
effects
in
fetuses
and
no
evidence
of
developmental
toxicity.
Thus,
pyraflufen
ethyl
is
neither
a
developmental
toxicant
nor
a
teratogen
in
the
rat.
Pyraflufen
ethyl
was
administered
by
gavage
during
gestation
and
showed
no
adverse
effects
on
dams
or
fetuses
at
dose
levels
of
0,
100,
300,
up
to
and
including
a
limit
dose
of
1,000
mg/
kg/
day.
The
maternal
and
developmental
toxicity
no
observe
adverse
effects
(
NOAELs)
were
both
>
1,000
mg/
kg/
day.
Results
from
a
developmental
toxicity
study
in
rabbits
conducted
with
pyrafluflen
ethyl
technical
also
indicated
no
evidence
of
teratogenicity
or
developmental
toxicity.
Thus,
pyraflufen
ethyl
technical
is
neither
a
developmental
toxicant
nor
a
teratogen
in
the
rabbit.
Rabbits
fed
pyraflufen
ethyl
at
0,
20,
60,
or
150
mg/
kg/
day,
resulted
in
severe
maternal
toxicity,
including
lethality,
from
gastrointestinal
irritation
at
doses
of
60
and
150
mg/
kg/
day.
The
maternal
NOAEL
was
20
mg/
kg/
day.
The
NOAEL
for
the
offspring
was
60
mg/
kg/
day,
based
on
increased
post
implantation
loss
observed
at
150
mg/
kg/
day.
Neither
the
rat
nor
the
rabbit
developmental
study
showed
evidence
of
unique
fetal
susceptibility
to
pyraflufen
ethyl.
In
a
multigeneration
rat
reproduction
study
conducted
at
dietary
concentrations
of
0,
100,
1,000
and
10,000
ppm,
pyraflufen
ethyl
had
no
effect
on
reproductive
parameters,
including
mating
indices,
fertility
index,
gestation
index,
duration
of
gestation,
numbers
of
implantation
sites,
numbers
and
morphology
of
epididymal
sperm,
and
estrous
cycle
at
any
dose
level.
Reproductive
performance
was
not
affected
by
pyraflufen
ethyl
at
the
highest
dose
level
of
10,000
ppm
(
male
721
to
844
mg/
kg/
day
and
female
813
to
901
mg/
kg/
day).
The
pup
NOAEL
was
1,000
ppm,
based
on
decreased
body
weight
in
the
F1
and
F2
male
and
female
pups
on
day
17
at
the
10,000
ppm
dose
level.
Results
from
the
reproduction
study
and
the
developmental
toxicity
studies
conducted
with
pyraflufen
ethyl
technical
show
no
increased
sensitivity
to
developing
offspring
as
compared
to
parental
animals,
because
the
NOAELs
for
growth
and
development
of
offspring
were
equal
to
or
greater
than
the
NOAELs
for
parental
or
maternal
toxicity.
4.
Subchronic
toxicity.
A
short
term
(
28
day)
dermal
study
in
rabbits
was
conducted
with
pyraflufen
ethyl
technical.
Pyraflufen
ethyl
was
administered
dermally
to
rats
for
28
days
at
dose
levels
of
0,
300,
and
1000
mg/
kg
day.
Slight,
transient
erythema
was
observed
during
week
3
in
3
treated
males.
This
finding
was
not
doserelated
was
not
considered
to
be
adverse,
and
the
relationship
to
the
test
material
administration
was
unclear.
The
NOAEL
was
considered
to
be
1,000
mg/
kg/
day.
A
90
day
rat
feeding
study
was
conducted
at
dose
levels
of
0,
200,
1,000,
5,000,
or
15,000
ppm
pyraflufenethyl
The
NOAEL
in
this
study
was
considered
to
be
1,000
ppm
(
85.6
mg/
kg/
day
for
males
and
95.4
mg/
kg/
day
for
females),
based
on
slightly
increased
phosphorous
concentrations
in
females
and
hepatocytic
hypertrophy
in
males
at
5,000
ppm.
In
addition,
the
highest
dose
of
15,000
ppm
resulted
in
erythocyte
toxicity,
mitochondrial
changes
in
the
hepatocytes
and
the
presence
of
Kupffer
cells.
Also,
at
the
high
dose
level
increased
kidney
weights
in
males
and
increased
absolute
and
relative
spleen
weights
in
both
sexes
were
observed.
In
a
90
day
oral
toxicity
study
in
dogs,
pyraflufen
ethyl
was
administered
via
capsule
at
dose
levels
of
0,
40,
200,
and
1,000
mg/
kg/
day.
No
treatmentrelated
findings
were
observed
and
the
NOAEL
was
determined
to
be
>
1,000
mg/
kg/
day.
At
the
limit
dose,
no
effects
in
body
weight
or
organ
weights,
clinical
chemistry,
hematology,
histopathology,
and
gross
pathology
were
observed.
To
determine
whether
the
test
material
was
absorbed
or
not,
plasma
was
collected
1
hour
after
administration
of
pyraflufen
ethyl
during
week
13.
The
detection
of
2
major
degradation
products,
E
1
and
E
9,
confirmed
the
adsorption
and
gastrointestinal
and
systemic
exposure
to
pyraflufen
ethyl.
5.
Chronic
toxicity.
A
1
year
chronic
dog
study
was
conducted
in
Beagle
dogs,
with
pyraflufen
ethyl
administered
orally
by
gelatin
capsule
at
doses
of
0,
40,
200,
and
1,000
mg/
kg/
day.
There
were
no
mortalities
and
no
clinical
signs
of
toxicity.
No
treatmentrelated
effects
were
noted
on
body
weights,
food
consumption,
hematology
and
clinical
chemistry
parameters,
urinalysis,
ophthmoscopy,
and
organ
weights.
No
macrosopic
or
microscopic
lesions
were
noted.
The
NOAEL
was
>
1,000
mg/
kg/
day.
In
a
2
year
chronic
toxicity/
oncogenicity
study,
pyraflufen
ethyl
was
administered
to
CD
rats
at
dietary
levels
of
0,
80,
400,
2,000,
or
10,000
ppm
(
equivalent
to
0,
3.4,
17.2,
86.7,
and
468.1
mg/
kg/
day
for
males
and
0,
4.4,
21.8,
111.5,
and
578.5
mg/
kg/
day
for
females).
Mortality
was
unaffected
by
treatment.
Body
weight
gain
was
statistically
significantly
depressed
for
those
rats
fed
10,000
ppm
at
1
year
compared
to
the
control.
Treatmentrelated
histopathology
was
seen
in
the
kidney,
liver,
and
bile
duct
at
10,
000
ppm.
At
2,000
and
10,000
ppm,
vacuoles
within
the
mitochondria
of
centriacinar
and
periacinar
hepatocytes
were
seen.
Effects
on
urine
volume,
urine
specific
gravity,
and
kidney
weights
were
seen
at
2,000
ppm
in
males.
The
NOAEL
was
17.2
mg/
kg/
day
for
males
and
21.8
mg/
kg/
day
for
females.
No
evidence
of
carcinogenicity
was
observed.
In
a
78
week
carcinogenicity
study,
mice
were
fed
pyraflufen
ethyl
in
the
diet
at
levels
of
0,
200,
1,000,
or
5,000
ppm
(
equivalent
to
0,
21,
110,
547
mg/
kg/
day
for
males
and
0.
20,
98,
524
mg/
kg/
day
for
females).
An
maximum
tolerance
dose
(
MTD)
was
reached
at
1,000
ppm,
based
on
increased
liver
weight
and
liver
histopathological
changes
(
including
necrosis)
seen
at
this
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Notices
feeding
level.
In
the
highest
dose
group,
effects
of
pyraflufen
ethyl
on
hematological
parameters
were
observed.
The
incidence
of
hepatocellular
adenoma
was
increased
in
animals
receiving
5,000
ppm,
compared
to
controls.
This
benign
tumor
was
likely
induced
by
the
adaptive
response
to
the
hepatocellular
degeneration
and
not
as
a
result
of
any
genotoxic
potential
of
pyraflufen
ethyl.
In
addition
the
response
was
observed
only
at
a
dose
level
that
was
in
excess
of
an
MTD.
6.
Animal
metabolism.
The
qualitative
nature
of
the
residues
of
pyraflufenethyl
and
its
acid
metabolite,
E
1,
in
animals
is
adequately
understood.
Pyraflufen
ethyl
is
rapidly
absorbed,
metabolized,
and
excreted
to
feces
and
urine,
with
greater
than
90%
of
the
administered
dose
excreted
within
24
hours
in
rats.
Based
on
metabolism
studies
with
goats,
hens,
and
rats,
there
is
no
reasonable
expectation
that
measurable
pyraflufen
ethyl
related
residues
will
occur
in
meat,
milk,
poultry,
or
eggs
from
the
proposed
use.
7.
Metabolite
toxicology.
No
toxicologically
significant
metabolites
were
detected
in
plant
or
animal
metabolism
studies
for
cotton
or
potatoes.
8.
Endocrine
disruption.
Chronic,
lifespan,
and
multigenerational
bioassays
in
mammals
and
acute
and
subchronic
studies
on
aquatic
organisms
and
wildlife
did
not
reveal
any
endocrine
effects
for
pyraflufen
ethyl.
Any
endocrine
related
effects
would
have
been
detected
in
this
comprehensive
series
of
required
tests.
The
probability
of
any
such
effect
due
to
agricultural
uses
of
pyraflufen
ethyl
is
negligible.
C.
Aggregate
Exposure
1.
Dietary
exposure.
The
potential
dietary
exposure
to
pyraflufen
ethyl
has
been
calculated
from
the
proposed
tolerances
for
use
on
cotton,
and
potato.
While
tolerances
at
the
LOQ
are
proposed
for
corn,
soybean,
and
wheat,
it
is
concluded
that
there
is
no
potential
for
residues
in
these
crops
and
thus
no
dietary
exposure.
These
very
conservative
chronic
dietary
exposure
estimates
used
the
tolerance
value
for
all
the
raw
agricultural
commodities.
In
addition
these
estimates
assume
that
100%
of
the
cotton
and
potato
crops
contain
pyraflufen
ethyl
residues.
i.
Food.
The
chronic
population
adjusted
dose
(
cPAD)
for
the
general
population,
based
on
residues
at
the
tolerance
levels
and
100%
of
potato
and
cotton
crops
treated
is
expected
to
be
approximately
0.000020
mg/
kg
bwt/
day
or
<
0.1%
of
the
reference
dose
(
RFD)
(
0.172
mg/
kg/
day).
Of
the
standard
subgroups
analyzed
by
the
dietary
exposure
evaluation
model
(
DEEM),
the
subgroup
with
the
highest
exposures
are
children
ages
1
to
6
years,
with
a
cPAD
of
0.000041
mg/
kg/
day
or
less
than
0.1%
of
the
RfD
mg/
kg/
day.
With
children
ages
7
to
12
with
exposures
of
0.000027
mg/
kg/
day,
the
exposure
is
less
than
0.1%
of
the
RfD.
ii.
Drinking
water.
As
a
screening
level
assessment
for
aggregate
exposure,
EPA
evaluates
drinking
water
level
of
comparison
(
DWLOC),
which
is
the
maximum
concentration
of
a
chemical
in
drinking
water
that
would
be
acceptable
in
terms
of
total
aggregate
exposure
to
that
chemical.
Based
on
the
chronic
RFD
of
0.172
mg/
kg/
day,
based
on
the
NOAEL
of
17.2
mg/
kg/
day
observed
in
the
chronic
rat
feeding
study
and
an
uncertainty
factor
(
UF)
of
100,
and
EPA's
default
factors
for
body
weight
and
drinking
water
consumption,
the
DWLOCs
have
been
calculated
to
assess
the
potential
dietary
exposure
from
residues
of
pyraflufenethyl
and
the
acid
metabolite,
E
1,
in
water.
For
the
adult
population,
the
chronic
DWLOC
was
35,086
parts
per
billion
(
ppb)
for
the
U.
S.
population,
and
for
children
10,172
ppb.
Chronic
drinking
water
exposure
analyses
were
calculated
using
EPA
screening
models,
screening
concentration
in
ground
water
(
SCIGROW
for
ground
water
and
generic
expected
environmental
concentration
(
GENEEC)
for
surface
water).
The
calculated
peak
GENEEC
value
for
the
acid
metabolite,
E
1,
the
major
degradation
of
pyraflufen
ethyl
which
is
formed
within
an
hour
of
addition
to
a
water
solution
or
to
soil,
is
0.3321
ppb
and
the
SCI
GROW
value
is
0.00024
ppb.
These
values
are
very
conservative
estimates
compared
to
the
values
derived
from
the
parent.
Nonetheless,
for
the
U.
S.
adult
population,
the
estimated
exposures
of
the
E
1
acid
metabolite
in
surface
water
and
ground
water
are
approximately
0.00094%
and
0.0000007%,
respectively,
of
the
DWLOC.
For
children,
the
estimated
exposures
of
the
acid
metabolite
in
surface
water
and
ground
water
are
approximately
0.0033%
and
0.000002%,
respectively
of
the
DWLOC.
Therefore,
the
exposures
to
drinking
water
from
the
acid
metabolite
are
negligible.
Based
on
the
dietary
and
drinking
water
assessments,
aggregate
exposure
to
residues
of
pyraflufen
ethyl
and
the
acid
metabolite
in
food
and
water
can
be
considered
to
be
negligible.
2.
Non
dietary
exposure.
It
is
being
proposed
that
pyraflufen
ethyl
be
registered
in
the
following
non
food
sites:
airports,
commercial
plants,
fence
lines,
farmyards,
and
farm
buildings;
storage
and
lumber
yards;
barrier
strips
and
firebreaks;
equipment
areas,
nurseries
and
ornamental
plantings;
established
ornamental
turf;
railroad,
roadside,
and
utility
rights
of
ways;
dry
ditches
and
ditch
banks;
fuel
tank
farms
and
pumping
stations;
other
similar
non
crop
areas.
Exposure
to
pyraflufenethyl
for
the
mixer/
loader/
groundboom/
aerial
applicator
was
calculated
using
the
Pesticides
Handlers
Exposure
Database
(
PHED).
These
PHED
assessments
were
based
on
a
70
kg
operator
treating
80
acres
per
day
using
ground
boom
equipment
on
both
cotton
and
potato
fields;
an
operator
treating
1,200
acres
per
day
using
aerial
equipment
on
cotton
fields;
and
an
operator
treating
350
acres
per
day
using
aerial
equipment
on
potato
fields
(
EPA,
1999)
at
a
maximum
use
rate
of
0.009
pounds
active
ingredient
per
acre
for
potato
and
0.0045
pounds
active
ingredient
per
acre
for
cotton.
All
workers
were
assumed
to
be
wearing
long
pants
and
long
sleeved
shirts.
Mixer
loaders
were
assumed
to
be
wearing
gloves,
while
aerial
and
ground
applicators
and
flaggers
were
not
assumed
to
be
wearing
gloves.
Margins
of
exposure
(
MOE)
for
acute
and
shortterm
exposure
were
calculated
utilizing
a
dermal
and
inhalation
NOAEL
of
20
mg/
kg/
day,
based
on
maternal
toxicity
seen
in
the
rabbit
teratology
study
at
60
mg/
kg/
day,
and
assuming
100%
dermal
absorption.
MOEs
for
intermediate
term
exposure
were
calculated
utilizing
a
dermal
endpoint
of
250
mg/
kg/
day,
the
systemic
NOAEL
from
the
28
day
dermal
toxicity
study
in
the
rat
with
the
2.5%
EC
formulation.
This
was
the
highest
dose
level
in
the
study
and
no
systemic
effects
were
seen
at
this
dose
level.
For
the
acute
inhalation
endpoint
we
used
86
mg/
kg/
day,
based
on
a
NOAEL
of
1,000
ppm
or
85.6
mg/
kg/
day
in
males
in
the
90
day
oral
feeding
study
in
the
rat.
The
combined
MOE
(
inhalation
plus
dermal)
for
pyraflufenethyl
was
greater
than
4,900
for
acute
and
short
term
exposure,
while
the
intermediate
term
total
MOEs
were
all
greater
than
56,000.
The
results
indicate
that
large
margins
of
safety
exist
for
the
proposed
uses
of
pyraflufen
ethyl.
D.
Cumulative
Effects
Pyraflufen
ethyl
belongs
to
the
protox
inhibitor
class
of
compounds,
and
chemically
is
a
3
phenylpyrazole.
The
herbicidal
activity
of
protox
inhibitors
is
due
to
the
inhibition
of
protoporphyrinogen
IX
oxidase.
All
relevant
toxicological
data
has
been
provided
to
EPA.
Chemicals
with
a
similar
mode
of
action,
i.
e.,
the
protox
inhibitors,
have
different
chemical
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Notices
structures
compared
to
pyraflufen
ethyl.
Although
other
protox
inhibitors
have
a
similar
herbicidal
mode
of
action,
there
is
no
information
available
to
suggest
that
these
compounds
exhibit
a
similar
toxicity
profile
in
the
mammalian
system.
We
are
aware
of
no
information
to
indicate
or
suggest
that
pyraflufenethyl
has
any
toxic
effects
on
mammals
that
would
be
cumulative
with
those
of
any
other
chemical.
Since
pyraflufenethyl
is
relatively
non
toxic,
cumulative
effects
of
residues
and
other
compounds
are
not
anticipated.
Therefore,
for
the
purposes
of
this
Food
Quality
Protection
Act
(
FQPA)
document,
there
should
be
no
consideration
of
cumulative
risk
that
would
require
assessment.
E.
Safety
Determination
1.
U.
S.
population.
Based
on
the
chronic
toxicity
data,
the
RfD
for
pyraflufen
ethyl
is
considered
to
be
0.172
mg/
kg/
day.
This
value
is
based
on
the
NOAEL
of
17.2
mg/
kg/
day
observed
in
the
chronic
rat
feeding
study
and
a
safety
(
uncertainty)
factor
of
100,
the
worse
case
estimate
of
chronic
dietary
exposure
of
pyraflufen
ethyl
from
cotton,
potatoes,
corn,
or
soybean
will
utilize
less
than
0.1%
of
the
RfD
for
the
general
U.
S.
population.
EPA
generally
has
no
concern
for
exposures
below
100%
of
the
RfD
because
the
RfD
represents
the
level
at
or
below
which
daily
aggregate
dietary
exposure
over
a
lifetime
will
not
pose
appreciable
risks
to
human
health.
The
complete
and
reliable
toxicity
data
and
the
conservative
chronic
exposure
assumptions
support
the
conclusion
that
there
is
a
reasonable
certainty
of
no
harm
from
dietary
(
food)
exposure
to
pyraflufen
ethyl
and
the
acid
metabolite
residues.
Moreover,
as
exposure
to
residues
of
pyraflufen
ethyl
and
the
acid
metabolite
via
water
is
negligible,
there
is
a
reasonable
certainty
of
no
harm
from
aggregate
exposure
to
pyraflufenethyl
and
the
acid
metabolite
residues.
2.
Infants
and
children.
The
conservative
estimates,
as
described
above,
indicate
that
chronic
dietary
exposure
of
pyraflufen
ethyl
and
the
acid
metabolite
from
cotton
and
potato
will
utilize
less
than
0.1%
of
the
RfD
for
non
nursing
infants,
less
than
0.1%
of
the
RfD
for
children
ages
1
to
6;
and
less
than
0.1%
of
the
RfD
for
all
populations
examined.
No
developmental,
reproductive,
or
fetotoxic
effects
were
noted
at
the
highest
doses
of
pyraflufenethyl
tested
in
guideline
reproductive
or
developmental
toxicity
studies.
Based
on
the
current
toxicological
data
requirements,
the
data
base
relative
to
prenatal
and
postnatal
effects
for
children
is
complete,
valid
and
reliable.
Results
from
the
teratology
studies
and
the
2
generation
reproduction
study
support
NOAELs
for
fetal/
developmental
effects
or
reproductive/
offspring
effects,
respectively,
equivalent
to
the
highest
concentrations
tested.
As
such,
there
is
no
increased
sensitivity
of
infants
and
children
to
residues
of
pyraflufen
ethyl.
Therefore,
an
additional
safety
(
uncertainty)
factor
is
not
warranted,
and
the
RfD
of
0.172
mg/
kg/
day,
which
utilizes
a
100
fold
safety
factor,
is
appropriate
to
assure
a
reasonable
certainty
of
no
harm
to
infants
and
children.
F.
International
Tolerances
There
is
no
Codex
maximum
residue
level
established
for
residues
of
pyraflufen
ethyl
and
the
acid
metabolite
on
any
crops.
[
FR
Doc.
02
29330
Filed
11
19
02;
8:
45
am]
BILLING
CODE
6560
50
S
ENVIRONMENTAL
PROTECTION
AGENCY
[
FRL
7410
5]
Notice
of
Availability
of
Enforcement
and
Compliance
History
Online
Web
Site
for
60
Day
Comment
Period
AGENCY:
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ACTION:
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request
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comments.
SUMMARY:
The
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within
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announces
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and
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Web
site,
Enforcement
and
Compliance
History
Online
(
ECHO),
which
contains
searchable,
facility
level
enforcement
and
compliance
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DATES:
Comments
must
be
submitted
no
later
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January
21,
2003.
ADDRESSES:
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Comments
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epa.
gov
as
a
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or
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or
mailed
to
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MC
2222A,
1200
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FOR
FURTHER
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CONTACT:
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at
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(
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564
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SUPPLEMENTARY
INFORMATION:
I.
ECHO
Background
EPA
is
committed
to
public
access
to
environmental
information
and
has
worked
to
develop
a
format
for
providing
Internet
access
to
facilitylevel
compliance
and
enforcement
information
contained
in
core
EPA
data
systems.
Though
the
data
included
within
ECHO
previously
were
available
to
the
public
primarily
through
Freedom
of
Information
Act
requests,
the
information
was
not
available
in
a
searchable
Web
format.
This
new
egovernment
initiative
makes
it
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easier
for
the
public
to
obtain
these
data
records
on
the
Internet.
EPA
has
worked
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State
governments
to
develop
the
content
of
the
site
and
ensure
accurate
data
and
has
pilot
tested
Internet
access.
A
Joint
EPA
State
Enforcement
and
Compliance
Public
Access
Workgroup
developed
the
template
for
the
type,
sources,
and
amount
of
data
to
be
included
within
ECHO.
This
workgroup,
developed
in
partnership
with
the
Environmental
Council
of
the
States
(
ECOS),
made
its
recommendations
in
June
2000.
EPA
has
field
tested
the
approach
and
the
data
through:
the
Sector
Facility
Indexing
Project
(
http://
www.
epa.
gov/
sfipmtn1/),
which
shows
data
for
a
limited
number
of
industrial
sectors,
and
a
four
State
pilot
in
the
Pacific
Northwest
(
http://
www.
epa.
gov/
idea/
region10).
Public
feedback
and
lessons
learned
from
these
projects
contributed
to
the
development
of
the
ECHO
site.
To
prepare
for
launch
of
ECHO,
EPA
and
the
States
conducted
a
comprehensive
data
review
to
ensure
high
quality
information.
ECHO
also
includes
on
the
site
an
online
error
reporting
process
that
allows
users
to
alert
EPA
and
the
States
to
possible
errors.
This
notice
announces
a
60
day
comment
period,
which
is
being
provided
to
give
interested
parties,
particularly
those
responsible
for
facilities
included
within
the
database,
the
opportunity
to
review
ECHO's
content,
design,
and
accuracy
of
data.
II.
ECHO
Data
ECHO
provides
integrated
compliance
and
enforcement
information
for
approximately
800,000
regulated
facilities
nationwide.
The
site
allows
users
to
find
facility
level
inspection,
violation,
enforcement
action,
and
penalty
information
for
the
past
two
years.
Facilities
regulated
under
the
Clean
Air
Act
(
CAA)
Stationary
Source
Program,
Clean
Water
Act
(
CWA)
National
Pollutant
Elimination
Discharge
System
(
NPDES),
and
Resource
Conservation
and
Recovery
Act
(
RCRA)
are
included.
ECHO
reports
provide
a
snapshot
of
a
facility's
environmental
record,
showing
dates
and
types
of
violations,
as
well
as
the
State
or
Federal
government's
response.
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| epa | 2024-06-07T20:31:42.075083 | regulations | {
"license": "Public Domain",
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} |
EPA-HQ-OPP-2002-0138-0001 | Notice | "2002-08-28T04:00:00" | Carbaryl: Availability of Risk Assessments. | 55233
Federal
Register
/
Vol.
67,
No.
167
/
Wednesday,
August
28,
2002
/
Notices
For
more
current
information:
http://
epa.
gov/
air/
caaac/
mobile
sources.
html.
Individuals
or
organizations
wishing
to
provide
comments
to
the
Subcommittee
should
submit
them
to
Ms.
Hogan
at
the
address
above
by
September
30,
2002.
The
Mobile
Sources
Technical
Review
Subcommittee
expects
that
public
statements
presented
at
its
meetings
will
not
be
repetitive
of
previously
submitted
oral
or
written
statements.
SUPPLEMENTARY
INFORMATION:
During
this
meeting,
the
Subcommittee
may
also
hear
progress
reports
from
some
of
its
workgroups
as
well
as
updates
and
announcements
on
activities
of
general
interest
to
attendees.
Dated:
August
21,
2002.
Margo
T.
Oge,
Director,
Office
of
Transportation
and
Air
Quality.
[FR
Doc.
02–
21947
Filed
8–
27–
02;
8:
45
am]
BILLING
CODE
6560–
50–
P
ENVIRONMENTAL
PROTECTION
AGENCY
[OPP–
2002–
0138;
FRL–
7194–
2]
Carbaryl;
Availability
of
Risk
Assessment
AGENCY:
Environmental
Protection
Agency
(EPA).
ACTION:
Notice.
SUMMARY:
This
notice
announces
the
availability
of
documents
that
were
developed
as
part
of
EPA's
process
for
making
pesticide
reregistration
eligibility
decisions
and
tolerance
reassessments
consistent
with
the
Federal
Food,
Drug,
and
Cosmetic
Act
(FFDCA),
as
amended
by
the
Food
Quality
Protection
Act
of
1996
(FQPA).
These
documents
are
the
human
health
and
environmental
fate
and
effects
risk
assessments
and
related
documents
for
carbaryl.
This
notice
also
starts
a
60–
day
public
comment
period
for
the
risk
assessments.
Comments
are
to
be
limited
to
issues
directly
associated
with
carbaryl
and
raised
by
the
risk
assessment
or
other
documents
placed
in
the
docket.
By
allowing
access
and
opportunity
for
comment
on
the
risk
assessment,
EPA
is
seeking
to
strengthen
stakeholder
involvement
and
help
ensure
that
our
decisions
under
FQPA
are
transparent
and
based
on
the
best
available
information.
The
tolerance
reassessment
process
will
ensure
that
the
United
States
continues
to
have
the
safest
and
most
abundant
food
supply.
The
Agency
cautions
that
the
risk
assessments
for
carbaryl
are
preliminary
and
that
further
refinements
may
be
appropriate.
Risk
assessments
reflect
only
the
work
and
analysis
conducted
as
of
the
time
they
were
produced
and
it
is
appropriate
that,
as
new
information
becomes
available
and/
or
additional
analyses
are
performed,
the
conclusions
they
contain
may
change.
DATES:
Comments,
identified
by
the
docket
ID
number
OPP–
2002–
0138
carbaryl,
must
be
received
on
or
before
October
28,
2002.
ADDRESSES:
Comments
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP–
2002–
0138
for
carbaryl
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
Anthony
Britten,
Special
Review
and
Reregistration
Division
(7508C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(703)
308–
8179;
email
address:
britten.
anthony@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
This
action
is
directed
to
the
public
in
general.
This
action
may,
however,
be
of
interest
to
a
wide
range
of
stakeholders,
including
environmental,
human
health,
and
agricultural
advocates;
the
chemical
industry;
pesticide
users;
and
members
of
the
public
interested
in
the
use
of
pesticides.
Since
other
entities
may
also
be
interested,
the
Agency
has
not
attempted
to
describe
all
the
specific
entities
that
may
be
affected
by
this
action.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
this
Document
and
Other
Related
Documents?
1.
Electronically.
You
may
obtain
electronic
copies
of
this
document,
and
certain
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
at
http://
www.
epa.
gov/.
On
the
Home
Page
select
``
Laws
and
Regulations,
''
``
Regulations
and
Proposed
Rules,
''
and
then
look
up
the
entry
for
this
document
under
the
``
Federal
Register—
Environmental
Documents.
''
You
can
also
go
directly
to
the
Federal
Register
listings
at
http://
www.
epa.
gov/
fedrgstr/.
In
addition,
copies
of
the
risk
assessment
and
certain
related
documents
for
carbaryl
may
also
be
accessed
at
http:
www.
epa.
gov/
pesticides/
reregistration/
status.
htm.
2.
In
person.
The
Agency
has
established
an
official
record
for
this
action
under
docket
ID
number
OPP–
2002–
0138.
The
official
record
consists
of
the
documents
specifically
referenced
in
this
action,
and
other
information
related
to
this
action,
including
any
information
claimed
as
Confidential
Business
Information
(CBI).
This
official
record
includes
the
documents
that
are
physically
located
in
the
docket,
as
well
as
the
documents
that
are
referenced
in
those
documents.
The
public
version
of
the
official
record
does
not
include
any
information
claimed
as
CBI.
The
public
version
of
the
official
record,
which
includes
printed,
paper
versions
of
any
electronic
comments
submitted
during
an
applicable
comment
period
is
available
for
inspection
in
the
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Rm.
119,
Crystal
Mall
#2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(703)
305–
5805.
C.
How
and
to
Whom
Do
I
Submit
Comments?
You
may
submit
comments
through
the
mail,
in
person,
or
electronically.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP–
2002–
0138
for
carbaryl
in
the
subject
line
on
the
first
page
of
your
response.
1.
By
mail.
Submit
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Information
Resources
and
Services
Division
(7502C),
Office
of
Pesticide
Programs
(OPP),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460.
2.
In
person
or
by
courier.
Deliver
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Information
Resources
and
Services
Division
(7502C),
Office
of
Pesticide
Programs
(OPP),
Environmental
Protection
Agency,
Rm.
119,
Crystal
Mall
#2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA.
The
PIRIB
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(703)
305–
5805.
3.
Electronically.
You
may
submit
your
comments
electronically
by
e
mail
to:
opp
docket@
epa.
gov,
or
you
can
submit
a
computer
disk
as
described
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Federal
Register
/
Vol.
67,
No.
167
/
Wednesday,
August
28,
2002
/
Notices
above.
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
Avoid
the
use
of
special
characters
and
any
form
of
encryption.
Electronic
submissions
will
be
accepted
in
WordPerfect
6.1/
8.0/
9.0
or
ASCII
file
format.
All
comments
in
electronic
form
must
be
identified
by
docket
ID
number
OPP–
2002–
0138.
Electronic
comments
may
also
be
filed
online
at
many
Federal
Depository
Libraries.
D.
How
Should
I
Handle
CBI
that
I
Want
to
Submit
to
the
Agency?
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
You
may
claim
information
that
you
submit
to
EPA
in
response
to
this
document
as
CBI
by
marking
any
part
or
all
of
that
information
as
CBI.
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
as
CBI
must
be
submitted
for
inclusion
in
the
public
version
of
the
official
record.
Information
not
marked
confidential
will
be
included
in
the
public
version
of
the
official
record
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
CBI,
please
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?
You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
1.
Explain
your
views
as
clearly
as
possible.
2.
Describe
any
assumptions
that
you
used.
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
your
views.
4.
If
you
estimate
potential
burden
or
costs,
explain
how
you
arrived
at
the
estimate
that
you
provide.
5.
Provide
specific
examples
to
illustrate
your
concerns.
6.
Offer
alternative
ways
to
improve
the
notice.
7.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
document.
8.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
ID
number
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
may
also
provide
the
name,
date,
and
Federal
Register
citation.
II.
Background
A.
What
Action
is
the
Agency
Taking?
EPA
is
making
available
risk
assessments
that
have
been
developed
as
part
of
the
Agency's
public
participation
process
for
making
reregistration
eligibility
and
tolerance
reassessment
decisions
for
the
organophosphate
and
other
pesticides
consistent
with
FFDCA,
as
amended
by
FQPA.
The
Agency's
human
health
and
environmental
fate
and
effects
risk
assessments
and
other
related
documents
for
carbaryl
are
available
in
the
individual
pesticide
docket.
As
additional
comments,
reviews,
and
risk
assessment
modifications
become
available,
these
will
also
be
docketed
for
carbaryl.
The
Agency
cautions
that
the
carbaryl
risk
assessments
are
preliminary
and
that
further
refinements
may
be
appropriate.
Risk
assessment
documents
reflect
only
the
work
and
analysis
conducted
as
of
the
time
they
were
produced
and
it
is
appropriate
that,
as
new
information
becomes
available
and/
or
additional
analyses
are
performed,
the
conclusions
they
contain
may
change.
EPA
is
providing
an
opportunity,
through
this
notice,
for
interested
parties
to
provide
written
comments
and
input
to
the
Agency
on
the
risk
assessment
for
the
pesticide
specified
in
this
notice.
Such
comments
and
input
could
address,
for
example,
the
availability
of
additional
data
to
further
refine
the
risk
assessments,
such
as
percent
crop
treated
information
or
submission
of
residue
data
from
food
processing
studies,
or
could
address
the
Agency's
risk
assessment
methodologies
and
assumptions
as
applied
to
this
specific
chemical.
Comments
should
be
limited
to
issues
raised
within
the
risk
assessment
and
associated
documents.
EPA
will
provide
other
opportunities
for
public
comment
on
other
science
issues
associated
with
the
pesticide
tolerance
reassessment
program.
Failure
to
comment
on
any
such
issues
as
part
of
this
opportunity
will
in
no
way
prejudice
or
limit
a
commenter's
opportunity
to
participate
fully
in
later
notice
and
comment
processes.
All
comments
should
be
submitted
by
October
28,
2002
using
the
methods
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.
Comments
will
become
part
of
the
Agency
record
for
carbaryl.
List
of
Subjects
Environmental
protection,
Chemicals,
Pesticides
and
pests.
Dated:
August
15,
2002.
Betty
Shackleford,
Acting
Director,
Special
Review
and
Reregistration
Division,
Office
of
Pesticide
Programs.
[FR
Doc.
02–
21586
Filed
8–
27–
02;
8:
45
am]
BILLING
CODE
6560–
50–
S
ENVIRONMENTAL
PROTECTION
AGENCY
[OPP–
2002–
0205;
FRL–
7193–
7]
Pesticide
Product;
Registration
Applications
AGENCY:
Environmental
Protection
Agency
(EPA).
ACTION:
Notice.
SUMMARY:
This
notice
announces
receipt
of
an
application
to
register
a
pesticide
product
containing
a
new
active
ingredient
not
included
in
any
previously
registered
product
pursuant
to
the
provisions
of
section
3(
c)(
4)
of
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(FIFRA),
as
amended.
DATES:
Written
comments,
identified
by
the
docket
ID
number
OPP–
2002–
0205,
must
be
received
on
or
before
September
27,
2002.
ADDRESSES:
Comments
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP–
2002–
0205
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
By
mail:
Raderrio
Wilkins,
Biopesticides
and
Pollution
Prevention
Division
(7511C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(703)
308–
1259
and
e
mail
address:
wilkins.
raderrio@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
You
may
be
affected
by
this
action
if
you
are
an
agricultural
producer,
food
manufacturer,
or
pesticide
manufacturer.
Potentially
affected
categories
and
entities
may
include,
but
are
not
limited
to:
Categories
NAICS
codes
Examples
of
potentially
affected
entities
Industry
111
Crop
production
112
Animal
production
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23>
2002
14:
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27,
2002
Jkt
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00000
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| epa | 2024-06-07T20:31:42.084326 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0001/content.txt"
} |
EPA-HQ-OPP-2002-0138-0002 | Supporting & Related Material | "2002-08-27T04:00:00" | null | Carbaryl
Summary
Uses
C
Carbaryl
(1
naphthyl
methylcarbamate)
is
a
widely
used
broad
spectrum
insecticide.
Approximately
3.9
million
pounds
(59
percent)
of
carbaryl
is
used
in
agriculture,
and
approximately
2.2
million
pounds
(34
percent)
of
carbaryl
is
used
by
homeowners
in
residential
settings.
The
remaining
uses
(7
percent)
are
in
the
nursery,
landscape
and
golf
course
industries.
C
Agricultural
uses
include
fruit
and
nut
trees,
many
types
of
fruits
and
vegetables,
and
grain
crops.
Homeowners
use
carbaryl
for
lawncare,
gardening,
and
petcare.
Other
uses
for
carbaryl
include
greenhouses,
sod
farms,
mosquito
adulticide
use,
and
a
special
local
need
use
of
carbaryl
on
oyster
beds
in
Washington
State.
Health
Effects
C
Carbaryl
can
cause
cholinesterase
inhibition
in
humans;
that
is,
it
can
overstimulate
the
nervous
system
causing
nausea,
dizziness,
confusion,
and
at
high
exposures,
respiratory
paralysis,
and
death.
C
Carbaryl
has
been
classified
as
"likely
to
be
carcinogenic
to
humans"
based
on
vascular
tumors
in
mice.
Risks
Dietary
Risks
from
Food
C
Acute
dietary
risk
estimates
with
Carbamate
Market
Basket
Survey
data
are
not
of
concern
for
the
entire
U.
S.
population,
including
infants
and
children.
Chronic
(cancer
and
noncancer)
dietary
risks
are
also
not
of
concern.
Dietary
Risks
from
Drinking
Water
C
Carbaryl
is
moderately
mobile
in
the
environment,
and
is
non
persistent.
C
Acute
surface
water
risks,
based
on
high
end
estimates
from
computer
modeling,
are
of
concern
for
all
populations
when
combined
with
food
exposures.
Chronic
(noncancer
and
cancer)
risks
from
surface
water
are
low
and
not
of
concern.
C
Groundwater
risks,
both
acute
and
chronic
(noncancer
and
cancer),
are
low
and
not
of
concern
when
combined
with
food
exposures.
Groundwater
concentrations
are
also
based
on
modeling
predictions.
Residential
risks
C
For
exposures
to
homeowner
handlers,
8
out
of
17
scenarios
resulted
in
noncancer
risks
of
concern.
For
carbaryl,
dermal
exposures
generally
determined
the
risk
levels.
Cancer
risks
for
all
17
scenarios
were
not
of
concern.
C
For
postapplication
exposure
to
homeowners,
only
one
scenario
(lawncare)
resulted
in
noncancer
risks
of
concern
for
adults.
For
children
10
12,
there
are
no
risks
of
concern;
however,
postapplication
exposures
are
of
concern
for
toddlers
for
pet
treatment
and
lawncare.
Cancer
postapplication
risks
are
low
for
all
scenarios
and
are
not
of
concern.
Aggregating
Dietary
and
Residential
Risk
C
Based
on
selected
residential
scenarios
that
are
not
of
concern
alone,
only
one
scenario
had
aggregate
risks
of
concern
when
combined
with
dietary
(food
and
drinking
water)
exposures.
Occupational
Exposures
C
Out
of
128
short
and
intermediate
term
handler
exposure
scenario
combinations,
only18
had
noncancer
risks
of
concern,
even
when
considering
the
highest
level
of
personal
protection
practicable
(including
engineering
controls).
Out
of
5
long
term
exposure
scenarios,
2
had
noncancer
risks
of
concern.
C
For
occupational
handler
cancer
risks,
8
of
the
128
handler
exposure
scenario
combinations
resulted
in
risks
of
concern
to
private
growers.
For
commercial
applicators,
21
scenarios
had
cancer
risks
of
concern.
C
Occupational
postapplication
risks
(noncancer
and
cancer)
are
of
concern
at
the
current
12
hour
REI
for
most
scenarios.
Ecological
Risks
C
For
nongranular
carbaryl
uses,
acute
risk
to
birds
is
low,
but
chronic
risk
to
birds
is
of
concern.
There
is
concern
for
both
acute
and
chronic
risk
to
mammals.
C
For
all
granular
uses,
there
is
concern
for
acute
risk
to
birds
and
small
mammals.
There
is
no
concern
for
acute
risk
to
larger
mammals.
C
There
is
concern
for
acute
risk
to
freshwater
fish
and
all
aquatic
invertebrates,
and
concern
for
chronic
risk
to
freshwater
aquatic
invertebrates.
There
is
no
concern
for
chronic
risk
to
freshwater
fish.
How
the
Risk
Picture
May
Change
The
registrant
is
completing
a
chemical
specific
biomonitoring
study
which
will
further
quantify
and
charcaterize
occupational
and
residential
use
risks,
and
a
targeted
surface
water
monitoring
study
to
further
characterize
the
presence
of
carbaryl
in
drinking
water.
| epa | 2024-06-07T20:31:42.088044 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0002/content.txt"
} |
EPA-HQ-OPP-2002-0138-0003 | Supporting & Related Material | "2002-08-27T04:00:00" | null | Overview
of
Carbaryl
Risk
Assessment
Introduction
This
document
summarizes
EPA's
human
health
and
ecological
risk
findings
and
conclusions
for
the
carbamate
pesticide
carbaryl,
as
presented
fully
in
the
revised
documents,
"Human
Health
Risk
Assessment:
Carbaryl"
dated
July
30,
2002
and
"Environmental
Fate
and
Ecological
Risk
Assessment
for
the
Reregistration
of
Carbaryl"
dated
August
17,
2002.
The
purpose
of
this
overview
is
to
help
the
reader
identify
the
key
features
and
findings
of
these
risk
assessments
and
better
understand
EPA's
conclusions.
We
developed
this
overview
in
response
to
comments
and
requests
from
the
public
which
indicated
that
the
risk
assessments
were
difficult
to
understand,
that
they
were
too
lengthy,
and
that
it
was
not
easy
to
compare
the
assessments
for
different
chemicals
due
to
differing
formats.
Carbaryl
is
a
carbamate
insecticide,
and
it
has
been
determined
that
N
methyl
carbamates
share
a
common
mechanism
of
toxicity:
the
inhibition
of
cholinesterase.
As
required
by
the
Food
Quality
Protection
Act
(FQPA),
EPA
will
consider
the
cumulative
risks
from
food,
water
and
non
occupational
exposure
resulting
from
all
relevant
uses
of
the
group
of
N
methyl
carbamates.
The
risk
estimates
summarized
in
this
document,
however,
are
for
carbaryl
alone.
Use
Profile
Carbaryl
(1
naphthyl
methylcarbamate)
is
one
of
the
most
widely
used
broad
spectrum
insecticides
in
agriculture,
professional
turf
management,
professional
ornamental
production,
and
in
residential
pet,
lawn,
and
garden
markets.
Based
on
sales
information
provided
by
the
technical
registrant
Aventis
in
September
1998,
it
appears
that
approximately
34%
of
carbaryl
is
used
by
homeowners
in
residential
settings,
59%
is
used
in
agriculture,
and
the
remaining
7%
is
used
in
the
nursery,
landscape
and
golf
course
industries.
According
to
Aventis,
this
information
still
reflects
current
trends.
C
Technical
Registrants.
The
technical
registrants
are
Aventis,
which
provided
the
primary
data
for
reregistration,
and
Burlington
Scientific
Corporation.
Aventis
is
now
owned
by
Bayer
CropScience,
and
is
still
corresponding
with
EPA
as
Aventis,
which
is
the
legally
recorded
name
on
EPA
pesticide
registrations.
C
Agricultural
Uses.
Carbaryl
is
used
in
agriculture
to
control
pests
on
terrestrial
food
crops,
including
fruit
and
nut
trees
(e.
g.,
apples,
pears,
almonds,
walnuts,
and
citrus),
many
types
of
fruits
and
vegetables
(e.
g.,
cucumbers,
tomatoes,
lettuce,
blackberries,
and
grapes),
and
grain
crops
(e.
g.,
corn,
rice,
sorghum,
and
wheat).
Use
Profile...
2
Based
on
the
Aventis
sales
data
cited
above,
approximately
3.9
million
pounds
of
active
ingredient
was
sold
to
the
agricultural
market.
Based
on
available
usage
information
for
the
years
1987
through
1996,
an
annual
estimate
of
carbaryl
total
domestic
usage
in
agriculture
averaged
approximately
2.5
million
pounds
of
active
ingredient
for
over
1.5
million
acres
treated.
Its
largest
agricultural
markets
(measured
as
the
percentage
of
pounds
active
ingredient
used
annually)
are
pecans
(12%),
apples
(9%),
grapes
(6%),
oranges
(5%),
alfalfa
(5%),
and
corn
(4%).
Most
of
this
use
was
in
Arkansas,
California,
Georgia,
Illinois,
Indiana,
Michigan,
Mississippi,
Ohio,
Oklahoma,
and
Texas.
Crops
with
a
high
percentage
of
the
total
U.
S.
planted
acres
treated
include
Chinese
cabbage
(57%),
asparagus
(43%),
cranberries
(39%),
Brussels
sprouts
(33%),
apples
(23%),
and
blueberries
(22%).
C
Residential
Uses.
Carbaryl
is
used
by
homeowners
for
lawncare,
gardening
(vegetables
and
ornamentals),
and
petcare.
Apart
from
petcare,
there
are
no
labels
for
indoor
uses.
Carbaryl
accounted
for
approximately
9%
of
the
total
residential
insecticide
market
and
was
ranked
fourth
on
the
list
behind
the
pyrethroids,
chlorpyrifos,
and
diazinon
(the
latter
two
are
now
being
removed
from
residential
markets,
so
changes
in
market
share
are
expected).
Dusts
(65%)
and
liquid
concentrates
(25%)
account
for
most
carbaryl
sales
in
the
residential
market
of
2
million
pounds
per
year.
C
Other
uses.
Carbaryl
is
used
for
ornamentals
and
turf,
including
production
facilities,
such
as
greenhouses
and
sod
farms.
It
is
used
on
golf
courses
and
on
residential
sites
treated
by
professional
applicators
(e.
g.,
annuals,
perennials,
and
shrubs).
Carbaryl
is
also
labeled
for
use
as
a
mosquito
adulticide,
and
EPA
has
assessed
the
risks
from
this
use.
Another
carbaryl
application
examined
in
the
risk
assessment
is
a
special
local
need
use
to
control
burrowing
shrimp
on
oyster
beds
in
Washington
State.
C
Formulations.
Carbaryl
formulations
include
baits,
dusts,
aerosol
sprays,
ready
to
use
pump
sprayers,
pet
collars,
pet
dips
and
shampoos,
flowable
concentrates,
emulsifiable
concentrates,
granulars,
soluble
concentrates,
water
dispersible
granules,
and
wettable
powders.
C
Methods
of
Application.
Typical
application
methods
in
agriculture
include
groundboom,
airblast,
chemigation,
and
aerial.
Carbaryl
can
also
be
applied
using
handheld
equipment
such
as
low
and
high
pressure
handwand
sprayers,
backpack
sprayers,
compressed
air
sprayers,
and
turfguns.
Homeowners
can
apply
carbaryl
with
equipment
that
includes
trigger
sprayers,
hose
end
sprayers,
ready
to
use
dust
packaging,
belly
grinders,
push
type
spreaders,
and
outdoor
foggers.
C
Application
Rates.
Carbaryl
rates
vary
depending
on
the
crop.
For
most
of
agriculture,
maximum
seasonal
rates
range
from
1
to
16
pounds
active
ingredient
per
acre.
Examples
of
high
rate
applications
are
tree
nut
crops
and
golf
courses.
Examples
of
low
rate
applications
are
certain
field
and
row
crops.
Depending
on
the
crop,
the
maximum
number
of
carbaryl
applications
per
season
can
range
from
1
to
8.
The
maximum,
single
application
rate
for
carbaryl
is
for
California
citrus
only,
specified
on
the
label
as
up
to
16
lb
ai/
acre.
3
Human
Health
Risk
Assessment
Dietary
Risk
from
Food
Carbaryl
risks
from
food
consumption
are
summarized
in
Table
1
below.
Risks
less
than
100%
of
the
Population
Adjusted
Dose
(PAD),
either
acute
(aPAD)
or
chronic
(cPAD),
are
not
of
concern
to
the
Agency.
The
aPAD
is
the
dose
at
which
a
person
could
be
exposed
on
any
given
day
and
no
adverse
health
effects
would
be
expected.
The
cPAD
is
the
dose
at
which
an
individual
could
be
exposed
over
the
course
of
a
lifetime
and
no
adverse
health
effects
would
be
expected.
For
the
cancer
dietary
assessment,
risks
less
than
1
x
10
6
are
not
of
concern
to
the
Agency.
Table
1.
Summary
of
Dietary
Exposure
and
Risk
for
Carbaryl
(including
Carbamate
Market
Basket
Survey
Data)
Population
Subgroup
Acute
(99.9
percentile)
Chronic
Cancer
Exposure
(mg/
kg/
day)*
%
aPAD
Exposure
(mg/
kg/
day)
%
cPAD
Risk
U.
S.
Population
0.
004580
46
0.000032
<1
2.8x
10
8
Infants
(<
1
year
old)
0.007272
73
0.000054
<1
NA
Children
1
6
0.
007546
75
0.000057
<1
NA
*mg/
kg/
day=
milligrams
per
kilogram
per
day.
The
acute
and
chronic
(noncancer)
dietary
food
risks
are
not
of
concern
to
the
Agency;
risks
are
less
than
100%
of
both
the
aPAD
and
cPAD.
Cancer
dietary
risk
is
also
not
of
concern
to
the
Agency
as
the
risk
to
the
general
population
of
2.8
x
10
8
is
less
than
1
x
10
6
.
Below
is
a
more
detailed
discussion
of
the
dietary
(food)
risk
estimates
in
Table
1.
Acute
Dietary
(Food)
Risk
Acute
dietary
(food)
risk
is
calculated
considering
what
is
eaten
in
one
day.
In
this
instance,
that
includes
the
full
range
of
consumption
values
as
well
as
the
range
of
residue
values
in
food.
C
For
carbaryl,
EPA
conducted
a
Tier
3/
4
dietary
risk
assessment,
which
is
currently
the
most
highly
refined
assessment
possible.
Dietary
exposure
was
determined
considering
the
level
of
carbaryl
residues
on
food
commodities
and
their
potential
consumption
by
multiple
subpopulations,
including
infants
and
children.
Acute
dietary
risk
was
then
calculated
by
comparing
dietary
exposure
to
the
aPAD.
C
As
shown
in
Table
1,
risk
estimates
for
all
commodities
are
less
than
100%
of
the
aPAD
for
all
subpopulations
when
considering
the
99.9th
percentile
of
exposure.
The
highest
exposed
Dietary
Risk
from
Food...
4
subpopulation
(children
1
6
years)
is
at
75%
of
the
aPAD,
and
the
general
population
is
at
46%
of
the
aPAD.
C
EPA
calculated
the
aPAD
and
dietary
risk
levels
for
carbaryl
using
the
following
data:
For
the
acute
dietary
assessment,
the
acute
No
Observed
Adverse
Effect
Level
(NOAEL)
is
1
mg/
kg/
day
from
a
developmental
neurotoxicity
study
in
rats.
Increased
incidence
of
neurological
(functional
observational
battery)
changes
were
observed
on
the
first
day
of
dosing
in
maternal
animals
at
a
Lowest
Observed
Adverse
Effect
Level
(LOAEL)
of
10
mg/
kg/
day.
The
uncertainty
factor
(UF)
is
100
for
acute
dietary
risk,
based
on
a
10x
for
standard
uncertainties
in
applying
animal
studies
to
humans
(interspecies
extrapolation)
and
a
10x
for
varying
effects
among
individuals
(intraspecies
variability).
The
acute
reference
dose
(acute
RfD)
is
0.01
mg/
kg/
day,
calculated
by
dividing
the
NOAEL
(1
mg/
kg/
day)
by
the
UF
(100).
The
10x
Food
Quality
Protection
Act
Safety
Factor
(FQPA
SF)
was
removed
(i.
e.,
is
1x)
for
all
population
subgroups.
The
Agency
determined
that
this
safety
factor
is
adequate
to
protect
infants
and
children
because
there
are
no
residual
uncertainties
in
the
exposure
databases,
the
toxicology
database
is
complete,
and
the
endpoint
and
NOAELs/
LOAEL
for
risk
assessment
were
well
defined.
In
the
toxicology
database,
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
in
rat
or
rabbit
fetuses
following
in
utero
exposure
in
the
standard
developmental
studies
was
observed.
There
was
a
low
level
of
concern
for
evidence
of
susceptibility
seen
in
the
developmental
neurotoxicity
study,
and
there
was
evidence
of
increased
susceptibility
in
offspring
in
the
2
generation
reproduction
study.
However,
the
Agency
believes
that
the
acute
and
chronic
RfDs
would
be
protective
of
these
effects
so
the
FQPA
SF
was
reduced
to
1x.
The
aPAD
is
0.01
mg/
kg/
day,
calculated
by
dividing
the
acute
RfD
(0.01
mg/
kg/
day)
by
the
FQPA
SF.
Since
the
FQPA
SF
is
1x,
the
aPAD
and
the
acute
RfD
are
identical.
The
acute
dietary
exposure
analysis
is
based
on
the
Dietary
Exposure
Evaluation
Model
(DEEM™),
that
uses
exposure
and
consumption
data
to
calculate
risk
as
a
percentage
of
the
PAD.
The
DEEM™
analysis
evaluated
individual
food
consumption
as
reported
by
respondents
in
the
USDA
1989
1992
Continuing
Surveys
for
Food
Intake
by
Individual
(CSFII).
For
acute
dietary
risk
assessments,
the
entire
distribution
of
consumption
events
for
individuals
is
multiplied
by
a
randomly
selected
distribution
of
residues
(probabilistic
analysis,
referred
to
as
"Monte
Carlo"
)
to
obtain
a
distribution
of
exposures.
The
CSFII
also
has
data
for
the
years
1994
through
1998.
Although
these
data
are
not
yet
routinely
used
in
individual
chemical
assessments,
EPA
has
developed
risk
estimates
for
Dietary
Risk
from
Food...
5
carbaryl
using
these
data.
The
risk
estimates
are,
in
general,
slightly
higher
than
those
using
the
1989
1992
data,
but
still
resulted
in
exposures
less
than
100%
of
the
aPAD.
The
anticipated
pesticide
residues
on
food
are
extensively
refined
for
the
acute
dietary
assessment
and
were
derived
from:
(1)
the
Carbamate
Market
Basket
Survey
(CMBS),
which
was
translated
to
similar
commodities
when
feasible;
(2)
monitoring
data
from
USDA's
Pesticide
Data
Program
(PDP);
(3)
FDA's
Surveillance
Monitoring
Program;
(4)
the
percentage
of
the
crop
treated
(estimated
maximum
percentage);
and
(5)
data
from
crop
field
trials
where
there
were
insufficient
PDP
or
FDA
monitoring
data.
Field
trial
data
were
used
for
the
following
commodities:
garden
beets,
turnips,
mustards,
dried
beans,
almonds,
pecans,
walnuts,
field
corn
grain,
rice,
flax
seed,
okra,
olive,
peanuts,
pistachio,
and
sunflower.
The
Carbamate
Market
Basket
Survey
(CMBS)
is
an
industry
sponsored,
year
long,
national
survey
of
carbamate
residues
on
selected
food
commodities
purchased
at
grocery
stores.
The
CMBS
collected
up
to
400
single
serve
samples
for
8
different
crops
(apple,
banana,
broccoli,
grape,
lettuce,
orange,
peach
and
tomato).
Residue
data
from
a
market
basket
survey
are
generally
considered
to
provide
a
close
approximation
to
residues
potentially
found
at
the
"dinner
plate."
Survey
data
are
generally
considered
the
most
appropriate
data
source
for
use
in
pesticide
risk
and
exposure
assessment.
Information
from
the
CMBS
is
being
used
in
carbamate
dietary
risk
assessments
in
conjunction
with
all
other
available
field
trial
and
monitoring
data.
It
is
acknowledged
that
the
sample
preparation
protocol
used
by
the
CMBS
introduces
a
degree
of
uncertainty
into
the
reported
survey
results.
The
protocol
(hand
rubbing
certain
commodities
during
the
rinsing
process)
created
a
potential
for
residue
loss
prior
to
analysis;
however,
the
degree
to
which
this
step
had
an
effect
on
residue
levels
cannot
be
quantified.
The
Agency
believes
these
survey
data
are
useful
to
the
carbaryl
dietary
risk
assessment,
as
they
tend
to
support
PDP
monitoring
data
findings
of
detectable
residues
on
commodities
important
to
the
diets
of
infants
and
children.
EPA
also
conducted
a
separate
assessment
using
solely
the
PDP/
FDA
monitoring
data
and
field
trial
data
for
a
better
understanding
of
the
overall
risks.
Use
of
this
data
set
provides
higher
risk
estimates
than
those
based
on
inclusion
of
the
CMBS
carbaryl
data.
For
example,
using
only
PDP/
FDA
and
field
trial
data,
exposure
for
all
infants
(less
than
1
year
old)
is
133%
of
the
aPAD,
and
exposure
for
children
1
through
6
is
110%
of
the
aPAD.
Dietary
Risk
from
Food...
6
Chronic
Dietary
(Food)
Risk
Chronic
(noncancer)
dietary
risk
from
food
is
calculated
by
using
the
average
consumption
value
for
foods
and
average
residue
values
on
those
foods
over
a
70
year
lifetime.
As
previously
shown
in
Table
1,
dietary
exposure
for
all
populations
is
less
than
1%
of
the
cPAD,
and
therefore
not
of
concern
to
the
Agency.
C
EPA
calculated
the
cPAD
and
dietary
risk
levels
for
carbaryl
using
the
following
data:
EPA
used
the
Lowest
Observed
Adverse
Effect
Level
(LOAEL)
of
3.1
mg/
kg/
day
for
the
chronic
dietary
assessment
based
on
a
1
year
chronic
toxicity
feeding
study
in
dogs.
Decreases
in
plasma
and
brain
cholinesterase
were
observed
in
females
at
this
dose.
Because
the
LOAEL
dose
was
the
lowest
dose
tested,
a
NOAEL
was
not
established.
The
uncertainty
factor
(UF)
is
300,
based
on
a
10x
for
standard
uncertainties
in
applying
animal
studies
to
humans
(interspecies
extrapolation)
and
a
10x
for
varying
effects
among
individuals
(intraspecies
variability),
as
well
as
a
3x
for
the
added
uncertainty
of
using
a
LOAEL
instead
of
a
NOAEL.
The
chronic
reference
dose
(chronic
RfD)
is
0.01
mg/
kg/
day,
calculated
by
dividing
the
LOAEL
(3.1
mg/
kg/
day)
by
the
UF
(300).
The
10x
Food
Quality
Protection
Act
safety
factor
(FQPA
SF)
was
removed
(i.
e.,
is
1x)
for
all
population
subgroups,
as
discussed
in
the
acute
dietary
section.
The
Agency
determined
that
this
safety
factor
was
adequate
to
protect
infants
and
children
because
there
are
no
residual
uncertainties
in
the
exposure
databases,
the
toxicology
database
is
complete,
and
the
endpoint
and
NOAELs/
LOAEL
for
risk
assessment
were
well
defined.
The
cPAD
is
0.01
mg/
kg/
day,
calculated
by
dividing
the
chronic
RfD
(0.01
mg/
kg/
day)
by
the
FQPA
SF.
Because
the
FQPA
SF
is
1x,
the
cPAD
and
the
chronic
RfD
are
identical.
The
chronic
dietary
exposure
analysis
is
based
on
the
Dietary
Exposure
Evaluation
Model
(DEEM™),
which
incorporates
exposure
and
consumption
data
to
calculate
risk
as
a
percentage
of
the
cPAD.
The
DEEM™
analysis
evaluated
individual
food
consumption
as
reported
by
respondents
in
the
USDA
1989
1992
Continuing
Surveys
for
Food
Intake
by
Individual
(CSFII).
For
chronic
dietary
risk
assessments,
a
3
day
average
consumption
for
each
subpopulation
is
combined
with
average
residues
in
commodities
to
determine
average
exposures.
Using
the
1994
1998
CSFII
data
does
not
alter
the
results.
The
anticipated
pesticide
residues
on
food
are
extensively
refined
for
the
chronic
dietary
assessment
for
food
and
derived
from:
(1)
monitoring
data
from
USDA's
Pesticide
Data
Dietary
Risk
from
Food...
7
Program
(PDP);
(2)
FDA's
Surveillance
Monitoring
Program;
(3)
the
percentage
of
the
crop
treated
(weighted
average);
and
(4)
data
from
crop
field
trials
where
there
were
insufficient
PDP
or
FDA
monitoring
data.
Field
trial
data
were
used
for
the
following
commodities:
garden
beets,
turnips,
mustards,
dried
beans,
almonds,
pecans,
walnuts,
field
corn
grain,
rice,
flax
seed,
okra,
olive,
peanuts,
pistachio,
and
sunflower.
CMBS
data
are
not
used
for
chronic
dietary
assessment
because
they
reflect
single
serving
residue
values.
Cancer
Dietary
(Food)
Risk
Cancer
dietary
risk
from
food
is
also
calculated
by
using
the
average
consumption
values
for
food
and
average
residue
values
for
those
foods
over
a
70
year
lifetime.
The
chronic
exposure
value
is
multiplied
by
a
linear
low
dose
response
factor
(Q1*),
based
on
animal
studies,
to
determine
the
lifetime
cancer
risk
estimate.
For
cancer
dietary
exposure,
risk
estimates
less
than
than
1
x
10
6
(1
in
1
million)
are
not
of
concern
to
the
Agency.
C
Carbaryl
is
classified
as
"likely
to
be
carcinogenic
to
humans,"
based
on
vascular
tumors
in
mice
(males).
The
unit
risk,
or
Q1*
value,
is
8.75
x
10
4
(mg/
kg/
day)
1
.
C
The
maximum
estimated
lifetime
cancer
dietary
(food)
risk
of
2.8
X
10
8
for
the
general
US
population
is
not
of
concern.
Use
of
the
1994
1998
CSFII
has
no
impact
on
the
overall
results.
Dietary
Risk
from
Drinking
Water
Drinking
water
exposure
to
pesticides
can
occur
through
surface
and
ground
water
contamination.
EPA
considers
both
acute
(one
day)
and
chronic
(lifetime)
drinking
water
risks
and
uses
either
modeling
or
actual
monitoring
data,
if
available
and
of
sufficient
quality,
to
estimate
those
risks.
To
determine
the
allowable
carbaryl
exposure
from
drinking
water,
or
the
Drinking
Water
Level
of
Comparison
(DWLOC),
EPA
first
looks
at
how
much
of
the
overall
allowable
dietary
risk
is
contributed
by
food.
For
carbaryl,
EPA
calculated
food
risk
including
the
results
of
the
Carbamate
Market
Basket
Survey.
The
DWLOC
is
the
amount
of
allowable
risk
left
for
exposure
through
drinking
water.
The
DWLOC
is
then
compared
to
a
drinking
water
estimated
environmental
concentration
(drinking
water
EEC).
If
the
DWLOC
is
higher
than
the
drinking
water
EEC,
then
the
risk
is
not
of
concern
to
the
Agency.
Below
is
a
discussion
of
the
drinking
water
EECs
for
carbaryl,
followed
by
a
comparison
of
the
DWLOCs
to
the
drinking
water
EECs
to
assess
risks.
Dietary
Risk
from
Drinking
Water...
8
Estimated
Environmental
Concentrations
for
Carbaryl
C
Carbaryl
is
fairly
mobile,
but
is
not
likely
to
persist
or
accumulate
in
the
environment.
As
such,
it
is
difficult
for
monitoring
studies
to
detect
peak
concentrations
that
can
occur.
EPA
determined
that
currently
available
monitoring
studies
for
carbaryl
are
limited
in
this
regard,
and
did
not
use
them
to
define
peak
values
for
carbaryl.
Instead,
EPA
used
computer
modeling
to
estimate
drinking
water
EECs
from
ground
and
surface
water
that
could
be
expected
from
normal
agricultural
use.
Modeling
is
designed
to
provide
a
high
end
estimate
of
exposure.
C
A
primary
degradate
of
carbaryl
is
1
naphthol.
The
Agency
is
not,
however,
concerned
about
levels
of
1
naphthol
in
drinking
water
for
this
assessment.
Due
to
the
limited
persistence
of
1
naphthol,
it
is
not
expected
to
be
found
in
significant
concentrations
resulting
from
carbaryl
applications,
and
even
if
found,
it
is
not
a
cholinesterase
inhibitor
nor
is
it
expected
to
be
carcinogenic.
C
Drinking
water
EECs
for
surface
water
were
estimated
using
computer
modeling
with
PRZM/
EXAMS
software,
scenarios
using
an
Index
Reservoir,
and
a
Percent
Crop
Area
factor.
Drinking
water
EECs
from
modeling
vary
depending
on
different
scenarios
for
geographic
location,
crop,
and
pesticide
application
rates.
C
Drinking
water
EECs
for
surface
water
were
estimated
using
five
crop
scenarios:
(1)
Ohio
Sweet
Corn,
(2)
Ohio
Field
Corn,
(3)
Oregon
Apples,
(4)
Minnesota
Sugar
Beets,
and
(5)
Florida
Citrus.
These
scenarios
were
selected
to
represent
the
range
of
crops
and
use
rates
likely
to
result
in
higher
environmental
concentrations.
These
scenarios
were
also
modeled
at
different
application
rates:
label
maximum
application
rate,
average
application
rate
(based
on
EPA's
data
review),
and
reported
maximum
application
rate
(from
DOANE
survey
data).
C
Drinking
water
EECs
for
groundwater
were
estimated
using
the
SCI
GROW
computer
model
based
on
the
upper
end
agricultural
application
rate
for
carbaryl
use
on
citrus.
SCI
GROW
provides
a
screening
value
to
use
in
determining
exposure
and
the
potential
risk
to
human
health.
Modeled
Risk
Estimates
The
DWLOCs
and
drinking
water
EECs
for
carbaryl
are
presented
in
Table
2.
Drinking
water
EECs
that
are
higher
than
DWLOCs
are
bolded.
Dietary
Risk
from
Drinking
Water...
9
Table
2.
DWLOCs
for
Combined
Food
and
Drinking
Water
Exposure
and
Drinking
Water
EECs
for
Carbaryl
at
the
Maximum
Label
Application
Rate
Population
Subgroup
Acute
DWLOCs
and
Drinking
Water
EECs
(ppb)
for
Surface
Water
Drinking
Water
EEC
(ppb)
for
Ground
Water
DWLOC
Drinking
water
EECs
(Modeling)
at
Maximum
Label
Application
Rates
Florida
Citrus
Oregon
Apples
Ohio
Sweet
Corn
Ohio
Field
Corn
Sugar
Beets
U.
S.
Population
188
494
144
37
30
19
0.8
All
Infants
(<
1yr)
27
494
144
37
30
19
Children
1
6
27
494
144
37
30
19
Children
7
12
38
494
144
37
30
19
Chronic
(noncancer)
DWLOCs
and
Drinking
Water
EECs
(ppb)
for
Surface
Water
U.
S.
Population
349
28
9
3
2
2
All
Infants
(<
1yr)
100
28
9
3
2
2
Children
1
6
99
28
9
3
2
2
Children
7
12
100
28
9
3
2
2
Cancer
DWLOCs
and
Drinking
Water
EECs
(ppb)
for
Surface
Water
U.
S.
Population
39
28
9
3
2
2
Acute
Drinking
Water
Risk
Estimates
for
Surface
Water
C
For
surface
water,
using
the
label
maximum
application
rates
for
carbaryl
in
the
model,
acute
drinking
water
EECs
exceed
the
DWLOCs
for
infants
(less
than
1
year)
and
children
(1
to
6
years)
for
combined
food
and
drinking
water
exposure
in
four
of
the
five
scenarios,
with
modeled
drinking
water
EECs
for
surface
water
ranging
from
30
ppb
for
Ohio
Field
Corn
to
approximately
500
ppb
for
Florida
Citrus.
Only
the
EECs
for
Minnesota
Sugar
Beets
(19
ppb)
were
less
that
than
the
DWLOCs
for
all
population
subgroups.
C
The
Agency
has
also
assessed
drinking
water
concentrations
based
on
average
application
rates
(based
on
usage
data)
and
reported
maximum
application
rates
(based
DOANE
survey
data).
These
rates
are
generally
lower
than
the
maximum
label
application
rate,
resulting
in
less
exposure
and
fewer
risks
of
concern.
Dietary
Risk
from
Drinking
Water...
10
C
The
highest
carbaryl
drinking
water
EEC
for
surface
water
(494
ppb),
which
is
from
the
maximum
label
application
rate
on
Florida
citrus,
is
presented
with
the
notation
that
the
majority
of
drinking
water
in
Florida
(greater
than
90%)
is
derived
from
ground
water.
Therefore,
potential
high
surface
water
concentrations
would
not
necessarily
indicate
widespread,
high
exposure.
The
aggregate
risk
assessment
therefore
uses
for
comparison
the
next
highest
drinking
water
EEC,
Oregon
apples
at
the
label
maximum
application
rate
(144
ppb).
Chronic
Drinking
Water
Risk
Estimates
Surface
Water
C
Chronic
(noncancer)
and
cancer
drinking
water
risk
estimates
from
surface
water
are
significantly
less
than
the
DWLOCs
and
are
not
of
concern
for
combined
food
and
drinking
water
exposures.
Chronic
(noncancer)
drinking
water
EECs
for
surface
water
range
from
0.7
to
28
ppb
for
both
average
and
maximum
rates,
significantly
less
than
the
chronic
DWLOCs
for
carbaryl.
Cancer
drinking
water
EECs
are
also
significantly
less
than
the
cancer
DWLOCs.
Drinking
Water
Risk
Estimates
for
Groundwater
C
The
modeled
drinking
water
EEC
for
groundwater
is
0.8
ppb,
and
is
significantly
less
than
the
acute
and
chronic
(cancer
and
noncancer)
DWLOCs
for
combined
food
and
drinking
water
exposure.
Monitoring
Data
C
EPA
lacks
a
targeted
drinking
water
monitoring
study
for
carbaryl
to
compare
with
the
screening
level
modeling
results
presented
above.
Carbaryl
is
the
second
most
widely
detected
insecticide
in
surface
water,
based
on
the
USGS
NAWQA
database,
with
a
significant
portion
apparently
transported
to
streams.
Out
of
5220
surface
water
samples
analyzed,
about
21%
(1082)
had
detections
greater
than
the
minimum
detection
limit.
The
maximum
observed
concentration
for
carbaryl
in
surface
water
from
the
non
targeted
USGS
NAWQA
study
is
5.5
ppb.
The
maximum
observed
concentration
from
a
California
state
surface
water
database
is
8.4
ppb,
cited
in
EPA's
environmental
risk
assessment
for
carbaryl.
Both
differ
significantly
from
the
494
ppb
peak
value
from
computer
modeling.
The
registrant
submitted
interim
results
from
an
ongoing
targeted
monitoring
study
of
carbaryl
surface
water
concentrations.
However,
the
interim
data
are
not
sufficient
to
serve
as
the
basis
for
the
drinking
water
EECs
in
this
risk
assessment.
Another
finding
in
the
NAWQA
data
is
that
streams
draining
urban
areas
showed
more
frequent
detections
and
higher
concentrations
than
streams
draining
agricultural
or
mixed
land
use
areas.
EPA
has
limited
tools
for
assessing
the
effects
of
pesticide
use
in
urban
and
suburban
settings
on
surface
water
and
groundwater
quality,
and
may
need
additional
data
to
provide
estimates
of
the
distribution
of
possible
exposures.
11
Residential
Risks
Use
Summary
C
Residents
can
receive
nondietary
exposures
to
carbaryl
by
mixing,
loading,
or
applying
pesticides
(residential
handler
exposure),
or
by
re
entering
an
area
after
treatment
(residential
post
application
exposure)
by
homeowners
or
commercial
pest
control
applicators.
Residential
exposures
are
broadly
defined
to
include
all
non
dietary,
nonoccupational
exposures,
including
recreational
activities
like
golfing,
and
any
other
exposures
than
can
occur
in
the
general
population.
C
Carbaryl
has
a
wide
variety
of
residential
uses,
including
lawns,
gardens,
ornamentals,
and
pets.
Other
than
pet
treatment,
there
are
no
registered
indoor
uses.
Carbaryl
is
used
on
golf
courses,
and
may
be
used
in
public
areas,
such
as
schools
or
parks.
Although
EPA
is
not
aware
of
public
health
uses
of
carbaryl
in
state
or
local
mosquito
control
programs,
it
is
labeled
as
a
mosquito
adulticide,
which
EPA
did
consider
in
the
risk
assessment.
There
is
also
potential
exposure
from
carbaryl
used
in
Washington
State
to
control
burrowing
shrimp
in
oyster
beds.
EPA
also
considered
this
special
local
need
(FIFRA
24c)
use
on
oyster
beds
in
the
risk
assessment.
C
Both
homeowners
(and
professional
applicators)
can
apply
carbaryl
by
many
methods,
including
trigger
sprayers,
hose
end
sprayers,
granular
spreaders,
ready
to
use
dust
packaging,
low
pressure
handwand
sprayers,
backpack
sprayers,
and
turfguns.
C
Residential
handlers
may
be
exposed
to
carbaryl
residues
via
the
dermal
(skin)
and
inhalation
routes.
Post
application
exposures
to
carbaryl
for
adults
are
most
likely
through
the
skin,
whereas
children
may
also
receive
oral
exposures
from
mouthing
behaviors
(i.
e.,
hand
tomouth
object
to
mouth,
and
soil
ingestion).
Noncancer
Toxicity
Summary
C
To
estimate
noncancer
residential
risks,
the
Agency
calculates
the
ratio
of
the
NOAEL
selected
for
risk
assessment
to
the
exposure.
This
margin
of
exposure
(MOE=
NOAEL/
exposure)
is
compared
to
a
target
MOE.
The
total
target
MOE
is
based
on
uncertainty
factors
(UFs)
that
are
routinely
applied
to
residential
risk
assessments:
10x
to
account
for
interspecies
extrapolation
and
10x
to
account
for
intraspecies
variations,
plus
any
additional
safety
factor
retained
due
to
concerns
unique
to
the
protection
of
infants
and
children
under
FQPA.
An
MOE
less
than
100
is
generally
of
concern
to
the
Agency.
C
For
carbaryl,
the
10x
FQPA
SF
has
been
removed
(i.
e.,
is
1x),
for
reasons
explained
above
in
the
acute
dietary
section.
Therefore,
the
target
MOE
for
short
and
intermediate
term
exposures
is
100.
For
long
term
exposures,
the
target
MOE
is
300,
because
the
lowest
dose
tested
in
the
long
term
study
was
the
LOAEL,
and
a
3x
uncertainty
factor
was
added
to
account
for
uncertainties
from
using
a
LOAEL
in
place
of
a
NOAEL.
The
only
residential
long
term
assessment
for
residential
use
is
the
postapplication
exposure
of
toddlers
to
pet
collars.
Residential
Risk...
12
C
The
NOAELs
and
LOAELs
used
in
the
residential
risk
assessment
are
summarized
below:
Short
and
intermediate
term
dermal
risk
assessments
for
carbaryl
are
based
on
a
NOAEL
of
20
mg/
kg/
day
from
a
28
day
dermal
toxicity
study
in
rats
using
technical
grade
carbaryl.
Decreases
in
red
blood
cell
cholinesterase
in
males
and
females,
and
decreases
in
brain
cholinesterase
in
males,
were
observed
at
the
systemic
LOAEL
of
50
mg/
kg/
day.
Short
term
inhalation
and
incidental,
nondietary
ingestion
risk
assessments
for
carbaryl
are
based
on
a
NOAEL
of
1
mg/
kg/
day
from
a
developmental
neurotoxicity
study
in
rats.
Increased
incidence
of
neurological
(functional
observational
battery)
changes
and
cholinesterase
inhibition
(red
blood
cell,
plasma,
whole
blood,
and
brain)
were
observed
at
the
LOAEL
of
10
mg/
kg/
day.
Since
an
oral
study
was
used
for
these
risk
assessments,
a
100%
absorption
factor
was
applied
to
extrapolate
for
the
inhalation
assessments.
Intermediate
term
inhalation
risk
assessments
for
carbaryl
are
based
on
a
NOAEL
of
1
mg/
kg/
day
from
a
subchronic
neurotoxicity
study
in
rats.
Increased
incidence
of
neurological
function
changes
and
cholinesterase
inhibition
(red
blood
cell,
plasma,
whole
blood,
and
brain)
were
observed
at
the
LOAEL
of
10
mg/
kg/
day.
Since
an
oral
study
was
used
for
these
risk
assessments,
a
100%
absorption
factor
was
applied
to
extrapolate
for
the
inhalation
assessments.
The
long
term
(greater
than
6
month)
exposure
assessment
for
pet
collars
is
based
on
a
3.1
mg/
kg/
day
LOAEL
from
a
1
year
chronic
toxicity
feeding
study
in
dogs.
Decreases
in
plasma
and
brain
cholinesterase
in
females
were
observed
at
this
dose.
Because
the
LOAEL
dose
was
the
lowest
dose
tested,
a
NOAEL
was
not
determined.
Therefore,
the
target
MOE
is
300
(which
includes
a
3x
uncertainty
factor
for
use
of
a
LOAEL
in
place
of
a
NOAEL).
Since
an
oral
study
was
used
for
these
risk
assessments,
a
12.7%
absorption
factor
was
used
to
extrapolate
for
the
dermal
assessments.
Noncancer
Risks
for
Residential
Handlers
C
EPA
assessed
only
short
term
(1
to
30
day)
exposures
for
residential
handlers.
Intermediate
term
exposures
(30
days
to
several
months)
are
unlikely
because
of
the
sporadic
nature
of
applications
by
homeowners.
C
Maximum
label
application
rates
and
use
information
specific
to
residential
products
served
as
the
basis
for
the
risk
calculations.
If
additional
information
was
available,
such
as
average
or
typical
rates,
EPA
used
these
values
to
allow
for
a
more
informed
risk
management
decision.
In
most
cases,
these
rates
differed
from
maximum
application
rates
by
about
a
factor
of
two.
C
Exposure
values
in
this
assessment
were
based
on
three
carbaryl
specific
residential
handler
studies.
EPA
also
used
two
other
sources
of
surrogate
information:
a
study
from
the
Outdoor
Residential
Risk...
13
Residential
Exposure
Task
Force,
of
which
Aventis
is
a
member,
and
the
Pesticide
Handlers
Exposure
Database
(PHED).
C
EPA
assessed
17
major
residential
handler
exposure
scenarios,
based
on
anticipated
use
patterns
and
current
labeling
for
carbaryl,
as
well
as
the
types
of
equipment
and
techniques
used
by
homeowners
to
apply
carbaryl.
Most
of
the
17
scenarios
include
more
than
one
site/
area/
rate
combination.
Table
3
presents
the
scenarios
EPA
considered
and
their
associated
risk
estimates.
Of
these
scenarios,
8
are
of
concern
(MOEs
are
less
100),
and
these
scenarios
and
MOEs
are
shown
in
bold.
In
all
cases,
dermal
exposure
is
the
primary
contributor
to
risk.
Table
3.
Carbaryl
Noncancer
MOEs
for
Combined
Short
term
Residential
Handler
Dermal
and
Inhalation
Exposures
#
Scenario
Descriptor
Use
Site
Amount
of
Carbaryl
Used
(lb
ai/
event)
Combined
Dermal
and
Inhalation
MOEs
1
Garden:
Ready
to
Use
Trigger
Sprayer
Vegetables/
Ornamentals
0.012
to
0.00075
2100
to
33730
2
Garden/
Ornamental
Dust
Vegetables/
Ornamentals
0.4
to
0.079
21
to
85
0.079*
107
3
Garden:
Hose
End
Sprayer
General
Use
(2%
soln)
2
21
Fire
Ants
0.75
55
Other
Uses:
Perimeter
Nuisance
Pests,
Vegetables,
Vegetables/
Ornamentals,
0.26
to
0.012
158
to
3427
4
Garden:
Low
Pressure
Handwand
General
Use
(2%
soln),
Perimeter
Nuisance
Pests,
Vegetables,
Ornamentals,
Fire
Ant
0.19
to
0.012
193
to
3056
5
Trees/
Ornamentals:
Low
Pressure
Handwand
Ornamentals,
Pome
Fruits,
Nuts/
Stone
Fruits,
Citrus
0.176
to
0.023
142
to
1084
6
Trees/
Ornamentals:
Hose
End
Sprayer
Ornamentals,
Pome
Fruits,
Nuts/
Stone
Fruits,
Citrus
0.5*
72
0.176
to
0.023
204
to
1559
7
Garden:
Backpack
Sprayer
General
Use
(2%
soln),
Perimeter
Nuisance
Pests,
Vegetables,
Vegetables/
Ornamentals,
Fire
Ants
0.19
to
0.012
1293
to
20468
8
Lawn
Care:
Hose
End
Sprayer
Lawn
(broadcast)
5
25
Lawn
(spot)
0.
25
495
9
Dogs:
Dusting
Dog
0.0026
142
0.1
4
0.05
7
10
Dogs:
Liquid
Application
Dog
0.001
14000000*
11
Granular
&
Baits
Lawn
Care:
Belly
Grinder
Lawn
(spot)
0.21
60
0.1
126
Residential
Risk...
#
Scenario
Descriptor
Use
Site
Amount
of
Carbaryl
Used
(lb
ai/
event)
Combined
Dermal
and
Inhalation
MOEs
14
12
Granular
&
Baits
Lawn
Care:
Push
Type
Spreader
Lawn
(broadcast)
4.2
to
2
477
to
1003
13
Granulars
&
Baits
By
Hand
Ornamentals
and
Gardens
0.
21
15
14
Aerosol
Various
0.08
65
15
Collars:
Pet
Dog
0.013
10800000*
16
Sprinkler
Can
(Source:
Scenario
6)
Ornamentals
(2%
solution)
0.1
359
17
Ornamental
Paint
On
Ornamentals
(2%
solution)
0.02
297
*Average
use
rate
based
on
exposure
study
data.
**
These
scenarios
reflect
dermal
MOEs
only,
and
are
based
on
EPA's
SOPs
for
Residential
Exposure
Assessment
as
opposed
to
monitoring
data.
Noncancer
Risks
for
Residential
Postapplication
Exposures
Several
carbaryl
specific
studies
were
used
in
developing
this
assessment,
including
a
turf
transferable
residue
study
conducted
in
California,
Georgia,
and
Pennsylvania
at
approximately
8
lb
ai/
acre.
This
study
was
conducted
using
the
standard
protocol
from
the
Outdoor
Residential
Exposure
Task
Force.
The
Agricultural
Reentry
Task
Force
conducted
several
dislodgeable
foliar
residue
studies
with
carbaryl.
The
olive
pruning
and
cabbage
weeding
studies
were
used
in
the
home
garden
risk
assessments.
EPA
assessed
the
risks
from
postapplication
exposure
to
carbaryl
residues
for
the
following
populations:
Adult
Residential
(homeowner);
Youth
aged
children
(10
12
years
old);
and
Toddlers
(3
year
olds).
EPA
considered
short
(1
to
30
days)
and
intermediate
term
(30
days
to
several
months)
exposures.
The
only
long
term
exposure
considered
(greater
than
6
months)
is
for
pet
collar
uses.
Adult
Residential
Postapplication
C
EPA
assessed
the
following
5
scenarios
for
adult
residential
postapplication
exposures:
residential
turf
for
lawncare
and
after
mosquito
control;
recreational
swimming
and
beach
activity
(following
oyster
bed
treatments);
golfing;
home
garden
exposure
to
deciduous
trees;
and
home
garden
exposure
to
fruiting
vegetables.
Within
each
scenario,
ranges
of
exposure
were
evaluated
for
different
application
rates,
duration
of
exposure,
and
postapplication
activities
(e.
g.,
weeding,
harvesting).
Of
the
5
scenarios,
only
1
is
of
concern:
short
term
risks
from
lawncare
(i.
e.,
heavy
yardwork).
C
On
the
day
of
application,
the
short
term
MOE
for
lawncare
is
43
at
an
application
rate
of
8
lb
ai/
acre.
After
about
5
days,
residues
dissipate
below
the
level
of
concern.
At
a
lower
application
rate
of
4
lb
ai/
acre,
the
MOE
on
the
day
of
application
is
88,
and
it
takes
about
1
day
for
residues
to
dissipate
below
the
level
of
concern.
All
the
remaining
MOEs
are
greater
than
500,
with
most
in
the
thousands
to
tens
of
thousands.
Similarly,
all
intermediate
term
exposures
for
residential
turf
are
greater
than
400.
Residential
Risk...
15
Youth
aged
Children
(10
to
12
year
olds)
C
Children
of
this
age
can
help
with
garden
maintenance,
and
therefore
are
considered
for
postapplication
activities
related
to
fruiting
vegetables
and
fruit
trees
(such
as
weeding
and
harvesting).
The
MOEs
for
these
activities,
both
short
and
intermediate
term,
were
all
greater
than
100
on
the
day
of
application,
and
therefore
not
of
concern.
The
lowest
MOEs
are
approximately
650
for
high
exposures
from
deciduous
trees
and
980
for
high
exposures
from
fruiting
vegetables;
the
rest
of
the
MOEs
are
significantly
greater
than
1000.
Toddlers
(3
year
olds)
C
Toddlers
were
selected
as
a
representative
population
for
turf
and
companion
animal
risk
assessments
to
provide
the
most
conservative
risk
estimates.
Exposures
from
turf
were
evaluated
separately
for
lawncare
uses
and
after
mosquito
control.
Beach
activity
following
oyster
bed
treatment
was
also
evaluated.
The
assessment
is
based
on
combined
risk
estimates
for
several
routes
of
exposure:
dermal,
hand
to
mouth,
object
to
mouth,
and
soil
ingestion.
C
Pet
treatments
result
in
short
term
risks
of
concern
for
toddlers,
(MOE
less
than100)
even
30
days
after
application,
regardless
of
whether
the
formulation
used
was
a
dust,
liquid
or
collar.
Hand
to
mouth
and
dermal
exposures
are
approximately
equal
contributors
to
the
overall
estimates
for
each
product
type.
Intermediate
term
risk
concerns
for
pet
treatments
are
similar
to
the
short
term
risk
concerns.
One
use,
pet
collars,
is
assessed
as
a
long
term
exposure,
and
is
also
of
concern
for
toddlers
(MOE=
43).
Pet
collars
are
assumed
to
be
worn
by
pets
all
of
the
time
so
long
term
exposures
to
toddlers
may
occur.
C
Treated
turf
exposures
(from
products
labeled
for
direct
application
to
turf)
also
result
in
short
term
risks
of
concern
for
toddlers.
The
MOEs
are
less
than
100
on
the
day
of
application
for
both
rates
considered,
4
lb
ai/
acre
(MOE=
11)
and
8
lb
ai/
acre
(MOE=
5).
These
applications
required
14
days
and
18
days,
respectively,
to
reach
the
target
MOE.
Intermediate
term
risks
to
toddlers
improve,
based
on
30
day
average
exposures
and
the
dissipation
rate
for
carbaryl,
but
the
MOEs
(91
and
45,
respectively)
are
still
of
concern.
Dermal
and
hand
to
mouth
exposures
are
the
key
contributors,
while
soil
ingestion
and
object
to
mouth
exposures
were
a
minor
contributors
to
the
total
risk
estimates.
C
Turf
exposures
following
application
of
carbaryl
as
a
mosquito
adulticide
are
not
of
concern,
regardless
of
how
applications
are
made
(i.
e.,
by
ground
or
air).
Both
short
term
(on
the
day
of
application)
and
intermediate
term
MOEs
are
equal
to
or
greater
than
the
target
MOE
of
100.
The
lowest
MOEs
are
approximately
450
for
aerial
application
and
850
for
ground
application,
with
the
remaining
MOEs
ranging
from
the
thousands
to
more
than
one
hundred
thousand.
C
Postapplication
risks
for
toddlers
playing
on
the
beach
after
oyster
bed
treatment
with
carbaryl
are
not
of
concern
to
the
Agency.
Short
term
MOEs
are
greater
than
100,
even
if
the
highest
monitored
sediment
concentration
value
from
any
study
available
to
the
Agency
was
used
as
the
basis
for
the
calculations.
The
intermediate
term
results
were
similar.
The
lowest
MOE
is
in
the
tens
of
thousands.
Residential
Risk...
16
Cancer
Risks
for
Residential
Handlers
C
Carbaryl
is
classified
as
"likely
to
be
carcinogenic
to
humans,"
based
on
increased
incidence
of
vascular
tumors
in
mice.
Cancer
risks
are
calculated
by
multiplying
the
Lifetime
Average
Daily
Dose
(LADD),
which
represents
dermal
and
inhalation
exposure
amortized
over
a
lifetime,
by
the
Q1*
or
unit
risk,
which
is
a
quantitative
dose
response
factor.
The
Q1*
for
carbaryl
is
8.75
x
10
4
(mg/
kg/
day)
1
.
C
For
the
17
handler
scenarios
considered
in
EPA's
residential
handler
assessment,
cancer
risks
are
not
of
concern
to
the
Agency;
the
risks
are
equal
to
or
less
than
1x10
6
(most
are
in
the
10
8
or
10
10
range)
when
evaluating
a
single
application
per
year.
C
EPA
also
calculated,
for
each
scenario,
the
maximum
number
of
days
of
exposure
per
year
that
could
occur
with
estimated
risks
still
at
or
below
the
1
x
10
6
risk
level
(i.
e.,
not
of
concern).
There
are
5
scenarios
where
the
maximum
number
of
exposures
at
or
below
the
1
x
10
6
risk
level
is
5
days
or
fewer
.
Cancer
Risks
for
Residential
Postapplication
Exposures
C
Postapplication
cancer
risks
were
calculated
only
for
adults
and
considered
the
same
scenarios
used
for
assessing
noncancer
risks.
C
For
all
scenarios
on
turf,
cancer
risks
are
not
of
concern
to
the
Agency;
risks
were
in
the
10
8
range
or
less
on
the
day
of
application
when
evaluating
a
single
reentry
event
per
year
during
lawncare
activities.
Risks
from
home
gardening,
golfing,
mosquito
control,
or
oyster
bed
treatment,
are
also
not
of
concern;
they
were
in
the
10
9
to
10
12
range
when
evaluating
a
single
reentry
event
per
year
on
the
day
of
application.
C
The
Agency
calculated,
for
each
scenario,
the
maximum
number
of
days
of
exposure
per
year
which
could
occur
and
risks
would
be
at
or
below
1
x
10
6
(i.
e.,
not
of
concern).
Values
range
from
20
to
over
365
days
per
year,
while
most
exceed
365
days
per
year
even
on
the
day
of
application.
Aggregating
Risks
from
Food,
Drinking
Water
and
Residential
Uses
Aggregate
risks
for
dietary
exposures
from
food
and
drinking
water
were
described
earlier.
This
section
describes
the
aggregate
(combined)
risk
from
food,
drinking
water
and
residential
exposures.
EPA
generally
does
not
calculate
aggregate
risks
when
dietary
or
residential
risks
are
already
of
concern.
In
this
case,
however,
EPA
did
generate
an
aggregate
risk
assessment
to
help
inform
risk
management
decisions.
Aggregating
Risks...
17
The
purpose
of
the
aggregate
assessment
is
to
identify
risks
that
become
a
concern
when
combined
with
others.
Therefore,
residential
risks
already
known
to
be
of
concern
alone
are
not
part
of
this
aggregate
assessment
for
carbaryl.
Instead,
EPA
selected
representative
scenarios
where
residential
risks
alone
are
not
already
of
concern.
These
scenarios
include
both
postapplication
and
handler
exposures.
Postapplication
exposures
include:
mosquito
control;
swimming/
beach
activity
(after
oyster
bed
treatments);
golfing;
and
garden
harvest.
The
handler
scenarios
are
mostly
at
the
average
application
rate
based
on
study
data.
The
maximum
application
rates
for
these
scenarios
were
not
used
because
they
are
already
of
concern
by
themselves.
The
handler
scenarios
selected
include:
application
of
dusts
to
gardens
and
pets;
hose
end
sprayer;
liquid
spray
spot
lawn
treatments;
and
broadcast
application
of
granulars
to
lawns.
C
After
aggregating
the
dietary
(food)
and
residential
exposures
not
already
of
concern,
EPA
determined,
for
each
assessed
activity,
the
DWLOC
(i.
e.,
the
allowable
room
left
for
drinking
water
exposure).
C
EPA
compared
the
calculated
DWLOCs
to
the
chronic
drinking
water
EECs
from
both
surface
water
and
ground
water.
For
drinking
water
EECs
from
surface
water,
results
from
carbaryl
use
on
Florida
citrus
and
Oregon
apples
were
used
for
comparison
with
the
DWLOC
because
they
are
the
two
highest
drinking
water
EECs
for
carbaryl.
Short
term
Aggregate
Risks
C
For
those
scenarios
that
are
not
residential
risk
concerns
alone,
all
DWLOCs
are
greater
than
the
chronic
drinking
water
EECs
(i.
e.,
are
not
of
concern),
except
for
the
DWLOC
(19
ppb)
for
adults
using
garden
dust
use
at
the
average
application
rate,
which
is
less
than
the
EEC
(28
ppb)
from
carbaryl
use
on
Florida
citrus
use.
The
DWLOC,
however,
is
greater
than
the
chronic
drinking
water
EECs
for
ground
water
(EEC
of
0.8
ppb),
or
for
surface
water
from
the
Oregon
apple
use
(9
ppb).
Intermediate
term
Aggregate
Risks
C
EPA
did
not
calculate
separate
intermediate
term
aggregate
risk
estimates.
The
results
would
essentially
be
the
same
as
the
short
term
aggregate
risk
estimates
because
the
hazard
inputs
are
numerically
identical.
Intermediate
term
postapplication
exposures,
though,
would
be
lower,
because
they
represent
a
30
day
average
rather
than
the
single
day
higher
exposure
estimate
used
for
short
term
exposures.
Cancer
Aggregate
Risks
C
Aggregate
cancer
risks
are
not
of
concern
for
any
subpopulation
regardless
of
the
source
of
drinking
water,
even
considering
the
high
end
drinking
water
EECs
for
Florida
citrus.
For
the
cancer
risks,
EPA
used
the
same
adult
scenarios
as
the
short
term
risk
assessment.
18
Occupational
Risk
C
The
occupational
risk
assessment
addresses
on
the
job
risks
to
pesticide
workers
who
may
be
exposed
to
carbaryl
when
mixing,
loading,
or
applying
a
pesticide
(i.
e.,
handlers),
and
when
entering
treated
sites
for
routine
tasks
(postapplication).
C
Occupational
noncancer
risk
is
being
measured
using
the
same
MOE
approach,
and
the
same
NOAELs
and
LOAELs,
as
are
used
in
the
residential
assessment
(see
the
Toxicology
Summary
heading
in
the
residential
section).
However,
the
occupational
assessment
does
not
consider
a
FQPA
SF
for
sensitive
populations
(infants
or
children).
Noncancer
Risks
for
Occupational
Handlers
Use
Scenarios
C
The
Agency
identified
28
major
occupational
exposure
scenarios
based
on
the
equipment
and
techniques
that
could
be
used
for
carbaryl
applications,
and
within
these
scenarios
there
are
128
different
crop/
rate/
acres
combinations.
These
scenarios
represent
short
term
(1
to
30
days)
and
intermediate
term
(30
days
to
several
months)
exposures.
A
few
scenarios
were
also
assessed
for
long
term
exposures
(more
than
180
days),
mostly
in
the
greenhouse
and
floriculture
industry
where
long
term
exposures
could
be
expected.
All
scenarios
present
the
combined
risk
from
dermal
and
inhalation
exposures.
C
Occupational
handler
risk
assessments
were
conducted
considering
eight
levels
of
personal
protection
based
on
different
combinations
of
the
following:
(1)
baseline
protection
(typical
work
clothing
or
a
long
sleeved
shirt
and
long
pants,
no
respiratory
protection
and
no
chemical
resistant
gloves);
(2)
minimum
personal
protective
equipment
(baseline
scenario
with
the
use
of
chemicalresistant
gloves
and
a
dust/
mist
respirator
with
a
protection
factor
of
5);
(3)
maximum
personal
protective
equipment
(baseline
scenario
with
the
use
of
an
additional
layer
of
clothing
(e.
g.,
a
pair
of
coveralls),
chemical
resistant
gloves,
and
an
air
purifying
respirator
with
a
protection
factor
of
10);
and
(4)
engineering
controls
(e.
g.,
closed
tractor
cab
or
closed
loading
system
for
granulars
or
liquids).
Current
labels
mostly
specify
single
layer
clothing,
chemical
resistant
gloves,
and
no
respirator.
C
The
maximum
application
rates
allowed
by
labels
were
used
in
the
risk
assessments.
If
additional
information
was
available,
such
as
average
or
typical
rates,
these
values
were
used
as
well
for
a
better
understanding
of
the
overall
risks.
C
The
unit
exposure
values
(mg
ai
exposure/
lb
ai
handled)
used
in
this
assessment
were
predominantly
based
on
the
Pesticide
Handlers
Exposure
Database
(PHED).
In
addition
to
PHED,
five
exposure
studies
were
used
by
the
Agency
to
estimate
exposures
for:
(1)
professional
dog
groomers;
(2)
granular
products
using
a
backpack
application
device
(two
studies);
(3)
a
ready
to
use
trigger
sprayer;
and
(4)
professional
lawncare
operators
using
granular
and
liquid
products.
Occupational
Risk...
19
Risk
Summary
Short
term
and
Intermediate
term
risks.
The
risk
assessment
for
short
and
intermediate
term
occupational
exposures
are
similar
because
the
toxicity
endpoints
(NOAELs)
are
numerically
the
same,
and
the
target
MOE
of
100
is
the
same
for
both
durations.
C
Out
of
the
total
of
128
crop/
rate/
area
combinations
assessed,
110
crop/
rate/
area
combinations
resulted
in
MOEs
that
meet
or
exceed
the
target
MOE
of
100
at
some
level
of
personal
protective
equipment
(PPE)
or
engineering
controls,
but
usually
at
a
higher
level
than
that
specified
on
the
current
label.
C
The
remaining
crop/
rate/
acerage
combinations
resulted
in
MOEs
that
are
less
than
the
target
MOE,
even
at
the
highest
practical
levels
of
PPE
and
engineering
controls.
Of
these,
8
are
aerial
uses;
2
are
wide
area
ground
uses;
3
are
granulars
and
baits
applied
by
spoon,
hand,
or
bellygrinder;
2
are
for
hand
held
devices;
and
1
is
for
an
animal
groomer
using
a
liquid
application.
Also,
2
crop/
rate/
area
combinations
for
poultry
use
were
assessed;
however,
Aventis
has
since
submitted
a
letter
to
EPA
requesting
voluntary
cancellation
of
the
poultry
use.
C
Table
4
below
summarizes
these
remaining
noncancer
risks
of
concern
for
occupational
handlers
for
short
and
intermediate
term
exposure
durations
that
do
not
meet
the
target
MOE,
even
after
considering
the
highest
level
of
PPE
and
engineering
controls.
Table
4.
Noncancer
Risks
of
Concern
for
Occupational
Handlers,
Short
and
IintermediateTerm
Durations
at
Highest
Level
of
PPE
Practical
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary:
Combined
Dermal/
Inhalation
MOEs
Mixer/
Loaders
1f
Dry
Flowable:
Wide
area
aerial
2
(rangeland/
forestry)
7500
58
3a
Liquid:
Aerial/
Chemigation
1.5
2
(wheat,
max
corn)
5
(stone
fruit)
1200
350
57
76
78
3f
Liquid:
Wide
area
aerial
2
(Range/
Forestry)
1
(Mosquito
adulticide)
7500
7500
9
18
3g
Liquid:
Wide
area
ground
1
(Mosquito
adulticide)
3000
45
4a
Wettable
Powders:
Aerial
1
2
(Wheat/
corn)
5
(stone
fruit)
1200
350
40
80
55
4f
Wettable
Powders:
Wide
area
aerial
2
(Range/
Forestry)
7500
6
Occupational
Risk...
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary:
Combined
Dermal/
Inhalation
MOEs
20
Applicators
5a
Aerial:
Agricultural
uses,
liquid
sprays
2
(max
corn)
1200
85
5b
Aerial:
Wide
area
uses,
liquid
sprays
2
(Range/
Forestry)
1
(Mosquito
adulticide
max
rate)
7500
7500
14
27
5c
Aerial:
Agricultural
uses,
granular
applications
2
(corn)
2
(corn)
1200
350
21
72
6b
Airblast:
Wide
area
uses,
liquid
sprays
1
(Mosquito
adulticide
max
rate)
3000
22
12
High
pressure
handwand
4
lb
ai/
100
gallons
1000
gallons
66
13
Animal
groomer,
liquid
application
0.
01
lb
ai/
dog
8
dogs
10
15
Granulars
&
baits
applied
by
hand
9
(Ornamentals
&
gardens)
1
4
16
Granulars
&
baits
applied
by
spoon
9
(Ornamentals
&
garderns)
1
75
Mixer/
Loader/
Applicators
17
Low
pressure,
high
volume
turfgun
(ORETF
Data)
8
(LCO
Use
on
turf)
5
94
20
Granular,
bellygrinder
9
(Turf)
1
27
Long
term
risks.
Only
a
few
occupational
uses
are
expected
to
result
in
long
term
exposures.
Of
5
scenarios
assessed,
3
meet
or
exceed
the
target
MOE
of
300
at
some
level
of
personal
protection.
The
two
scenarios
that
fail
to
meet
or
exceed
the
target
MOE
are
scenario
15:
granulars
&
baits
applied
by
hand;
and
scenario
16:
granulars
and
baits
applied
by
spoon.
Both
were
assessed
at
the
maximum
application
rate
of
9
lb
ai/
acre.
Noncancer
Risks
for
Occupational
Postapplication
Exposures
C
For
postapplication
exposures,
EPA
calculates
the
minimum
length
of
time
required
following
an
application
before
residues
have
dissipated
to
the
level
where
the
calculated
MOE
reaches
the
target
MOE.
EPA
uses
this
information
to
determine
restricted
entry
intervals
(REIs),
the
time
period
after
which
workers
are
allowed
to
reenter
a
treated
area.
For
carbaryl,
the
current
label
specifies
a
12
hour
REI.
C
At
the
current
REI,
short
term
MOEs
are
of
concern
(i.
e.,
less
than
100)
for
all
but
the
lowest
exposure
scenarios
in
some
crops.
Table
6
summarizes
the
crop
groups
that
result
in
risks
of
concern
during
short,
intermediate
and
long
term
postapplication
exposures,
and
at
different
levels
of
exposure
depending
on
the
activity
and
contact
with
treated
surfaces.
Occupational
Risk...
21
Table
6.
Noncancer
Risks
of
Concern
for
Occupational
Postapplication
Exposures
Low
Exposure
(e.
g.,
irrigation)
Medium
Exposure
(e.
g.,
scouting)
High
Exposure
(e.
g.,
hand
harvesting)
Short
term
Exposure
Duration
(1
to
30
days)
Crop
and
#
of
days
to
reach
target
MOE
Cut
Flowers
7
Evergreen
Fruit
Trees
6
Brassica
6
Crop
and
#
of
days
to
reach
target
MOE
Cut
Flowers
9
Evergreen
Fruit
Trees
17
Brassica
9
Bunch/
Bundle
Group
6
Low/
Medium
Field/
Row
Crops
3
Tall
Field/
Row
Crops
4
Sugarcane
3
Root
vegetables
4
Curbit
Vegetables
4
Leafy
Vegetables
4
Stem/
stalk
Vegetables
1
Vine/
Trellis
Group
2
Crop
and
#
of
days
to
reach
target
MOE
Cut
Flowers
12
Evergreen
Fruit
Trees
(No
high
exposure)
Brassica
11
Bunch/
Bundle
Group
8
Low/
Medium
Field/
Row
Crops
5
Tall
Field/
Row
Crops
11
Sugarcane
7
Root
vegetables
7
Curbit
Vegetables
7
Leafy
Vegetables
7
Stem/
stalk
Vegetables
5
Vine/
Trellis
Group
11
Low
Berry
4
Fruiting
Vegetable
2
Deciduous
Fruit
Trees
8
Nut
Trees
11
Turf/
Sod
14
Intermediateterm
Exposure
Duration
(30
days
to
several
months)
None
Crop
(calculated
MOE)
Evergreen
Fruit
Trees
(MOE=
59)
Crop
(calculated
MOE)
Cut
Flowers
(MOE=
57)
Evergreen
Fruit
Trees
(No
high
exposure)
Brassica
(MOE=
79)
Tall
Field/
Row
Crops
(MOE=
97)
Turf/
Sod
(MOE=
46)
Vine/
Trellis
(MOE=
79)
Long
Term
Exposure
Duration
(greater
than
six
months)
None
None
Crop
(calculated
MOE)
Cut
flower
industry
(MOE=
69).
Cancer
Risks
for
Occupational
Handlers
Occupational
cancer
risks
equal
to
or
less
than
1
x
10
6
(1
in
1
million)
are
not
of
concern
to
the
Agency.
The
Agency
also
carefully
examines
uses
with
estimated
risks
in
the
10
6
to
10
4
range
to
seek
cost
effective
ways
of
reducing
risks.
If
carcinogenic
risks
are
in
this
range
for
occupational
handlers,
increased
levels
of
personal
protective
equipment
(PPE)
or
engineering
controls
are
added
to
the
extent
practical.
The
Agency
considered
two
distinct
populations
for
the
carbaryl
cancer
risk
assessment:
private
growers,
at
10
applications
per
year,
and
commercial
applicators
at
30
applications
per
year.
Occupational
Risk...
22
Private
growers
(10
applications
per
year).
C
Of
the
128
scenario
combinations
considered
for
private
growers,
all
scenarios
have
risks
less
than
1
x
10
6
at
some
level
of
PPE
or
engineering
controls,
except
for
8
scenarios
that
have
risks
between
1
x10
4
and
10
6
.
Of
these
8
scenarios,
only
1
needed
a
higher
level
of
PPE
than
specified
on
the
current
label
to
have
risks
in
this
range.
Commercial
applicators
(30
applications
per
year)
C
Of
the128
scenario
combinations
considered
for
commercial
applicators,
all
have
risks
less
than
1
x
10
6
at
some
level
of
PPE
or
engineering
controls,
except
for
21
scenarios
that
have
risks
between
1
x
10
4
and
10
6
.
Of
these
21
scenarios,
only
1
needed
a
higher
level
of
PPE
than
specified
on
the
current
label
to
have
risks
in
this
range.
Cancer
Risks
for
Occupational
Postapplication
Exposures
Based
on
a
10
6
risk
concern,
the
current
REI
appears
adequate
to
address
cancer
risks
for
many
crop/
activity
combinations.
But
for
higher
exposure
situations,
longer
duration
REIs
are
necessary
for
risks
to
cease
to
be
of
concern
(<
10
6
).
In
all
cases,
REIs
based
on
cancer
risks
are
less
restrictive
or
similar
(i.
e.,
within
a
day
or
two
of
application
for
commercial
farmworkers)
than
those
based
on
the
noncancer
effects
of
carbaryl.
In
no
cases
do
cancer
risks
indicate
more
restrictive
REIs
than
for
noncancer
risks
calculated
for
the
corresponding
exposure
scenario.
Private
growers
(10
applications
per
year).
C
All
scenarios
have
risks
in
the
10
6
range,
except
for
one
scenario
(very
high
exposure
for
tall
field/
row
crops),
which
was
in
the
10
5
range.
All
risks
in
the
10
6
range
take
up
to
approximately
5
days
to
fall
below
1
x
10
6
.
The
risk
in
the
10
5
range
takes
23
days
to
fall
below
1
x
10
6
.
Commercial
farmworkers
(30
applications
per
year).
C
All
scenarios
had
cancer
risks
in
the10
6
range
or
less
on
the
day
of
application
at
the
current
REI,
except
for
two
very
high
exposure
activities
(hand
harvesting).
All
risks
in
the
10
6
range
take
approximately
8
days
to
fall
below
1
x
10
6
.
The
two
very
high
exposure
activities,
for
tall
field/
row
crops
and
vine/
trellis
crop
groups,
have
risks
in
the
10
5
range
on
the
day
of
application,
and
take
31
and
13
days,
respectively,
to
fall
below
1
x
10
6
.
Human
and
Domestic
Animal
Incidents
C
The
Agency
evaluated
reports
of
human
carbaryl
poisonings
and
adverse
reactions
associated
with
its
use
from
the
following
sources:
OPP
Incident
Data
System
(IDS);
Poison
Control
Centers'
Toxic
Exposure
Surveillance
System;
California
Department
of
Pesticide
Regulation;
the
National
Pesticide
Telecommunications
Network,
now
the
National
Pesticide
Information
Center
(NPIC);
open
literature;
and
an
unpublished
study
submitted
by
the
registrant.
Human
and
Domestic
Animal
Incidents...
23
C
The
data
from
IDS
indicated
that
a
majority
of
incidents
associated
with
carbaryl
exposure
involved
dermal
reactions.
A
number
of
other
cases
involved
asthmatics
and
people
who
experienced
hives
and
other
allergic
type
reactions.
According
to
California
data,
about
half
of
the
cases
involved
skin
and
eye
effects
in
handlers.
About
a
quarter
of
the
skin
reactions
were
due
to
workers
who
were
exposed
to
residues
on
crops.
Reports
from
the
literature
are
very
limited
but
tend
to
support
the
finding
that
carbaryl
has
irritant
properties.
C
The
Poison
Control
Center
cases
involving
nonoccupational
adult
exposure
and
exposures
of
older
children
showed
an
increased
risk
in
five
of
the
six
measures
used
for
comparing
carbaryl
incidents
to
all
other
pesticides.
The
carbaryl
cases
were
almost
twice
as
likely
to
require
serious
health
care
(hospitalization
or
treatment
in
a
critical
care
unit)
and
were
two
and
a
half
times
more
likely
to
experience
major
medical
outcome
(life
threatening
effects
or
significant
residual
disability)
than
other
pesticides.
This
pattern
of
increased
risk
was
not
seen
among
occupational
reports
or
in
young
children,
which
may
mean
that
careless
handling
by
non
professionals
is
a
particular
hazard.
In
addition,
five
case
report
studies
suggested
that
carbaryl
may
be
a
cause
of
chronic
neurological
or
psychological
problems.
C
The
incident
reports
on
domestic
animals
in
IDS
were
evaluated.
Based
on
limited
data,
there
is
some
evidence
that
young
kittens
may
be
susceptible
to
adverse
reactions
to
carbaryl.
Ecological
Risk
Assessment
To
estimate
potential
ecological
risk,
EPA
integrates
the
results
of
exposure
and
ecotoxicity
using
the
quotient
method.
Risk
quotients
(RQs)
are
calculated
by
dividing
acute
and
chronic
exposure
estimates
by
ecotoxicity
values
for
various
wildlife
species.
RQs
are
then
compared
to
levels
of
concern
(LOCs);
the
higher
the
RQ,
the
greater
the
potential
risk.
Environmental
Fate
Information
C
Carbaryl
dissipates
in
the
environment
by
abiotic
and
microbially
mediated
degradation.
The
major
degradation
product
is
1
naphthol,
which
is
further
degraded
to
CO2.
Carbaryl
is
stable
to
hydrolysis
in
acidic
conditions,
but
hydrolyzes
in
neutral
(half
life=
12
days)
and
alkaline
environments
(pH
9
half
life=
3.2
hours).
Under
aerobic
conditions
the
compound
degrades
rapidly
by
microbial
metabolism,
with
half
lives
of
4
to
5
days
in
soil
and
aquatic
environments.
In
anaerobic
environments
metabolism
is
much
slower,
with
half
lives
on
the
order
of
2
to
3
months.
Carbaryl
is
moderately
mobile
in
the
environment.
Open
literature
information
suggests
that
its
major
degradate,
1
naphthol,
is
less
persistent
and
less
mobile
than
carbaryl.
Ecological
Risk...
24
Nontarget
Terrestrial
Animal
Risk
Risks
to
Birds
C
The
acute
LOC
for
birds
is
0.5
and
the
chronic
LOC
is
1.0.
C
Nongranular
uses
of
carbaryl
are
not
expected
to
pose
an
acute
risk
to
birds.
Of
the
scenarios
assessed,
none
exceed
the
LOC
for
birds
in
any
weight
class.
Most
nongranular
uses
of
carbaryl
do
pose
a
chronic
risk
for
birds.
C
Granular
uses
of
carbaryl
pose
an
acute
risk
for
20
gram
birds
(highest
RQ
is
4.76).
For
180
gram
birds,
uses
that
exceed
the
LOC
are
for
trees/
ornamentals,
turf
grass,
and
tick
control.
For
1000
gram
birds,
no
granular
uses
exceed
the
LOC.
Risks
to
Mammals
C
The
acute
LOC
for
mammals
is
0.5
and
the
chronic
LOC
is
1.0.
C
Nongranular
uses,
at
the
maximum
label
application
rate,
pose
acute
risks
above
the
LOC
for
mammals
(highest
RQ
is
12).
At
rates
below
the
maximum
label
rate
(i.
e.,
the
maximum
reported
application
rate
and
the
average
application
rate),
most
uses
exceed
the
LOC
for
15
gram
mammals
feeding
on
short
grass
(highest
RQ
is
11).
Practically
all
nongranular
uses
pose
chronic
risks
that
exceed
the
LOC
(highest
RQ
is
48).
C
Granular
uses,
at
maximum
label
rates,
pose
acute
risks
that
exceed
the
LOC
for
15
gram
and
35
gram
mammals
(highest
RQs
are
21.1
and
9.04
respectively),
indicating
that
all
granular
carbaryl
uses
pose
an
acute
risk
to
the
smaller
mammalian
species.
For
1000
gram
mammals,
no
acute
risks
exceed
the
LOC.
Nontarget
Aquatic
Animal
Risk
C
The
acute
LOC
for
aquatic
animals
is
0.5
and
the
chronic
LOC
is
1.0.
C
EPA
examined
risks
to
aquatic
animals
for
estimated
environment
concentrations
in
surface
water
based
on
five
crop
scenarios
for
carbaryl:
apples,
field
corn,
sweet
corn,
citrus
and
sugar
beets.
C
Acute
risks
for
freshwater
fish
exceed
the
LOC
for
use
on
citrus
(highest
RQ
is
1.1).
No
scenario
exceeded
the
chronic
risk
LOC.
C
Acute
risks
for
estuarine/
marine
fish
do
not
exceed
the
LOC
for
any
scenario.
Data
are
not
available
to
assess
chronic
risks.
C
Acute
risks
for
aquatic
invertebrates,
both
freshwater
and
estuarine/
marine,
exceed
the
LOC
for
all
scenarios.
The
acute
RQs
range
from
0.8
to
161.
Chronic
risks
for
freshwater
aquatic
Ecological
Risk...
25
invertebrates
exceed
the
chronic
LOC.
The
chronic
RQs
range
from
1.7
to
91.
No
data
are
available
to
assess
chronic
risks
to
estuarine/
marine
invertebrates.
Risks
to
Honeybees
C
Carbaryl
is
highly
toxic
to
honey
bees.
It
is
one
of
the
pesticides
more
often
implicated
in
bee
mortality
incidents,
ranking
second
and
third
respectively,
in
two
separate
bee
kill
surveys
undertaken
in
1997
by
the
Washington
State
Department
of
Agriculture
and
the
American
Beekeeping
Federation.
Nontarget
Plant
Risk
C
For
terrestrial
plants,
the
carbaryl
label
indicates
that
carbaryl
may
cause
injury
to
tender
foliage
if
applied
when
foliage
is
wet
or
during
high
humidity,
and
carbaryl
may
also
harm
Boston
ivy,
Virginia
creeper,
or
maidenhair
fern.
A
few
reported
incidents
cite
injury
to
vegetable
crops
(potatoes,
tomatoes,
cabbage
and
broccoli).
However,
not
all
guideline
data
are
available
to
fully
assess
carbaryl
risk
to
terrestrial
plants.
C
For
aquatic
plants,
based
on
the
single
core
green
alga
study
available,
the
acute
risk
LOC
is
not
exceeded
for
any
of
the
five
scenarios
modeled,
even
at
maximum
label
rates.
However,
not
all
guideline
data
are
available
to
fully
assess
carbaryl
risk
to
aquatic
plants.
Risks
to
Endangered
Species
C
Acute
endangered
species
LOCs
for
terrestrial
animals
(birds
and
mammals)
is
0.1;
for
aquatic
animals
(freshwater
or
marine/
estuarine
fish
and
invertebrates)
it
is
0.05.
°
Granular
uses
exceed
the
endangered
species
LOC
for
20
gram
birds,
and
they
also
exceed
the
LOC
for
180
gram
birds
for
most
agricultural
uses
of
carbaryl.
For
1000
gram
birds,
RQs
exceed
the
endangered
species
LOC
for
the
trees
and
ornamentals,
turf
grass,
and
tick
control
uses.
Nongranular
uses
of
carbaryl
do
not
exceed
the
avian
endangered
species
LOC
based
on
acute
exposure.
C
The
endangered
species
LOC
for
mammals
is
met
or
exceeded
for
all
uses
at
three
application
rates:
maximum
label,
average
(based
on
usage
data),
and
maximum
reported
(based
on
DOANE
survey).
°
All
carbaryl
uses,
even
at
less
than
maximum
label
rates,
exceed
the
endangered
species
LOC
for
both
freshwater
and
marine/
estuarine
aquatic
invertebrates.
At
less
than
maximum
label
rates,
the
endangered
species
LOC
is
exceeded
for
freshwater
fish
only,
based
on
the
high
end
citrus
use
scenario,
and
not
exceeded
for
estuarine/
marine
fish
for
any
of
the
five
use
scenarios
modeled.
Ecological
Risk...
26
Ecological
Incident
Data
C
Carbaryl
does
not
rank
high
in
the
list
of
pesticides
responsible
for
bird
or
mammal
mortality,
based
on
information
available
in
the
USEPA
Ecological
Incident
Information
System.
Three
bird
kill
incidents,
classified
as
"probable,"
involved
blackbirds,
ducks,
starlings,
and
grackles
in
Virginia,
New
Jersey,
and
South
Carolina.
Only
two
incidents
involved
small
mammals
(grey
and
ground
squirrels,
mole,
and
rabbit)
in
South
Carolina
and
Virginia.
Numerous
bee
kill
incidents
have
been
recorded
for
carbaryl
in
several
states
including
North
Carolina,
South
Dakota
and
Washington.
Additionally,
several
incidents
on
vegetable
crops,
including
damage
to
potatoes,
tomatoes,
cabbage,
and
broccoli
were
classified
as
"probable."
Summary
of
Pending
Data
Aventis
has
completed
and
is
in
the
process
of
submitting
(in
August
2002)
a
residential
postapplication
biomonitoring
study
for
lawn,
and
either
a
vegetable
garden
or
ornamental
flowers.
Aventis
will
also
submit
(in
October
2002)
a
biomonitoring
study
of
field
workers
during
harvesting
and
hand
thinning
operations
in
apples
and
cherries.
Also,
Aventis
is
a
member
of
the
Residential
Exposure
Joint
Venture
(REJV),
which
is
a
group
of
companies
conducting
a
survey
of
homeowners
to
ascertain
how
consumer
pesticide
products
are
used
(e.
g.,
rate,
frequency,
pests,
etc.).
Aventis
recently
submitted
an
analysis
of
this
data
for
carbaryl,
which
could
be
used
to
refine
the
exposure
estimates
in
this
assessment
by
refining
the
amounts
of
carbaryl
used
per
homeowner
application.
In
September
2002,
Aventis
will
submit
the
final
results
of
their
surface
water
monitoring
study
for
drinking
water.
| epa | 2024-06-07T20:31:42.091603 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0003/content.txt"
} |
EPA-HQ-OPP-2002-0138-0004 | Supporting & Related Material | "2002-07-31T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
Office
of
Prevention,
Pesticides
and
Toxic
Substances
July
30,
2002
SUBJECT:
Carbaryl:
Revised
HED
Risk
Assessment
Public
Comment
Period,
Error
Correction
Comments
Incorporated,
DP
Barcode:
D284580,
PC
Code:
056801
FROM:
Jeffrey
L.
Dawson,
Chemist/
Risk
Assessor
Reregistration
Branch
1
Health
Effects
Division
(7509C)
THRU:
Whang
Phang,
PhD,
Branch
Senior
Scientist
Reregistration
Branch
1
Health
Effects
Division
(7509C)
TO:
Anthony
Britten,
Chemical
Review
Manager
Reregistration
Branch
3
Special
Review
&
Reregistration
Division
(7508C)
Attached
is
HED's
risk
assessment
of
the
insecticide
carbaryl
for
purposes
of
issuing
a
Reregistration
Eligibility
Decision
(RED)
Document
for
this
active
ingredient.
This
document
is
based
on
several
disciplinary
science
chapters
which
include:
Toxicology
D282980;
Dietary
Exposure
D281419
Product
and
Residue
Chemistry
D283328;
Occupational
and
Residential
Exposure
D281418
and
Estimated
Environmental
Concentrations
D240841.
This
chapter
reflects
recent
changes
in
the
hazard
component
based
on
the
submission
of
additional
toxicology
studies
(reproductive
and
three
21
day
dermal
toxicity
studies);
changes
in
endpoint
selection;
revision
of
the
Q1*
for
cancer
risk
assessment;
and
a
reduction
in
the
FQPA
SF
from
10
to
1.
Modifications
to
the
occupational
and
residential
assessment
includes
changes
in
the
calculations
for
pet
uses;
the
use
of
recently
submitted
ARTF
transfer
coefficients
for
greenhouse
crops;
and
changes
to
the
updated
duration
policy
for
delineating
short
and
intermediate
term
exposures.
Also,
mosquito
adulticide
and
carbaryl
use
on
oyster
beds
in
Washington
state
have
been
quantitatively
addressed.
Modifications
to
the
dietary
risk
assessment
include:
the
use
of
updated
processing
factors;
deletion
of
some
use
patterns;
and
the
use
of
additional
residue
data.
This
document
also
addresses
error
correction
comments
raised
by
Aventis
Crop
Sciences
included
in
the
document
Human
Health
Risk
Assessment
and
Supporting
Documents
Phase
1
Error
Correction
(July
12,
2002)
that
were
submitted
on
the
previous
version
of
this
assessment
(D281420,
Dated
June
7,
2002).
Reviewers:
RARC
(6/
6/
01
Report),
Revision
(6/
7/
02)
Reviewed
By
Paula
Deschamp
HUMAN
HEALTH
RISK
ASSESSMENT
Carbaryl
U.
S.
Environmental
Protection
Agency
Office
of
Pesticide
Programs
Health
Effects
Division
(7509C)
Jeffrey
L.
Dawson,
Chemist/
Risk
Assessor
Date:
July
30,
2002
HUMAN
HEALTH
RISK
ASSESSMENT
Carbaryl
Risk
Assessment
Team:
Risk
Assessor:
Jeffrey
L.
Dawson,
Dietary
Risk:
Felecia
Fort
Product
and
Residue
Chemistry:
Felecia
Fort
Occupational
and
Residential
Exposure:
Jeffrey
L.
Dawson
Epidemiology:
Jerome
Blondell,
MPH,
PhD
Monica
Spann,
MPH
Virginia
Dobozy,
VMD,
MPH
Toxicology:
Virginia
Dobozy,
VMD,
MPH
Drinking
Water
Estimates:
R.
David
Jones,
Ph.
D.
E.
Laurence
Libelo,
Ph.
D.
Table
of
Contents
1.
0
EXECUTIVE
SUMMARY......................................................
5
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
.....................
17
2.
1
Chemical
Structure
and
Identification.......................................
17
2.
2
Physical
Properties
of
Carbaryl
............................................
18
3.
0
HAZARD
CHARACTERIZATION
..............................................
19
3.1
Hazard
Profile
.........................................................
19
3.
2
FQPA
Considerations
...................................................
22
3.2.1
Determination
of
Susceptibility
......................................
22
3.2.2
Degree
of
Concern
Analysis
and
Residual
Uncertainties
..................
23
3.3
Dose
Response
Assessment
...............................................
24
3.4
Endocrine
Disruption
....................................................
26
4.0
NON
OCCUPATIONAL
RISK
ASSESSMENT
AND
CHARACTERIZATION
...........
27
4.
1
Summary
of
Registered
Uses..............................................
27
4.2
Dietary
Risk
Assessment
.................................................
31
4.2.1
Residue
Profile
...................................................
32
4.2.2
Acute
Dietary
Risk
Assessment
......................................
34
4.2.3
Chronic
Dietary
Risk
Assessment
....................................
37
4.2.4
Cancer
Dietary
Risk
Assessment
.....................................
38
4.2.5
Characterization/
Uncertainties
of
the
Dietary
Risk
Estimates
..............
38
4.
3
Estimated
Environmental
Concentrations
In
Water
............................
39
4.3.1
Environmental
Fate
Characteristics
...................................
39
4.3.2
Monitoring
Data
..................................................
40
4.3.3
Modeling
EECs
..................................................
41
4.
4
Residential
Risk
Assessment
..............................................
43
4.4.1
Home
Uses
......................................................
44
4.4.2
Residential
Handler
Risk
Assessment
.................................
44
4.4.2.1
Residential
Handler
Noncancer
Risks
...........................
47
4.4.2.2
Residential
Handler
Cancer
Risks
..............................
51
4.4.3
Residential
Postapplication
Risk
Assessment
...........................
54
4.4.3.1
Residential
Postapplication
Exposure
and
Noncancer
Risks
..........
59
4.4.3.2
Residential
Postapplication
Exposure
and
Risks
For
Cancer
.........
65
4.4.4
Residential
Risk
Characterization
....................................
66
4.4.5
Exposure
from
the
Use
of
Tobacco
...................................
69
4.4.6
Other
Residential
Exposures
........................................
69
5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
.............
70
5.
1
Calculation
of
Aggregate
Risks
and
DWLOCs
................................
70
5.
2
Acute
Dietary
Aggregate
Risks
and
DWLOCs
................................
73
5.
3
Chronic
Dietary
Aggregate
Risks
and
DWLOCs
..............................
73
5.
4
Short
term
Aggregate
Risks
and
DWLOCs...................................
74
5.
5
Intermediate
term
Aggregate
Risks
and
DWLOCs.............................
75
5.
6
Aggregate
Cancer
Risks
and
DWLOCs......................................
76
5.
7
Summary
of
Aggregate
Risks
.............................................
77
6.
0
CUMULATIVE
RISK.........................................................
78
7.0
OCCUPATIONAL
RISK
ASSESSMENT
.........................................
79
7.
1
Occupational
Handler
Risk
Assessment
.....................................
79
7.1.1
Occupational
Handler
Non
Cancer
Risks
..............................
84
7.1.2
Occupational
Handler
Cancer
Risks
..................................
88
7.2
Postapplication
Exposures
and
Risks
.......................................
92
7.2.1
Occupational
Postapplication
Noncancer
Risks
.........................
95
7.2.2
Occupational
Postapplication
Exposure
and
Risk
Estimates
for
Cancer
.......
98
7.
3
Occupational
Risk
Characterization
.......................................
101
8.0
HUMAN
AND
DOMESTIC
ANIMAL
INCIDENT
DATA
REVIEW
..................
104
9.0
DATA
NEEDS
..............................................................
105
APPENDIX
1:
Toxicology
Profile
APPENDIX
2:
Incident
Review
5
1.0
EXECUTIVE
SUMMARY
The
Health
Effects
Division
(HED)
of
EPA's
Office
of
Pesticide
Programs
has
evaluated
the
carbaryl
database
and
conducted
a
human
health
risk
assessment
for
the
reregistration
of
the
chemical.
Carbaryl
is
a
list
A
reregistration
chemical.
Carbaryl
is
also
subject
to
court
specified
deadlines
resulting
from
a
Natural
Resources
Defense
Council
(NRDC)
petition
of
the
Agency.
This
assessment
incorporates
error
corrections
and
begins
phase
3
of
the
public
participation
process.
Use
Patterns:
Carbaryl
[1
napthyl
methylcarbamate]
is
one
of
the
most
widely
used
broadspectrum
insecticides
in
agriculture,
professional
turf
management,
professional
ornamental
production,
and
in
the
residential
pet,
lawn
and
garden
markets.
Carbaryl
formulations
include
baits,
dusts,
pet
collars,
flowable
concentrates,
emulsifiable
concentrates,
granulars,
soluble
concentrates,
and
wettable
powders.
Carbaryl
is
used
in
agriculture
to
control
pests
on
terrestrial
food
crops
including
fruit
and
nut
trees
(e.
g.,
apples,
pears,
almonds,
walnuts,
and
citrus),
many
types
of
fruit
and
vegetables
(e.
g.,
cucumbers,
tomatoes,
lettuce,
blackberries,
and
grapes),
and
grain
crops
(e.
g.,
corn,
rice,
sorghum,
and
wheat).
Carbaryl
is
also
used
for
direct
animal
treatments
to
control
pests
on
companion
animals
such
as
dogs
and
cats.
There
are
other
uses
for
ornamentals
and
turf,
including
production
facilities
such
as
greenhouses,
golf
courses,
and
residential
sites
that
can
be
treated
by
professional
applicators
(e.
g.,
annuals,
perennials,
shrubs).
Carbaryl
can
also
be
used
by
homeowners
on
lawns,
for
home
and
garden
uses,
and
on
companion
animals.
There
are
no
labels
for
indoor
uses
within
a
residence.
In
agriculture,
groundboom,
airblast,
and
aerial
applications
are
typical.
Other
applications
can
also
be
made
using
handheld
equipment
such
as
low
pressure
handwand
sprayers,
backpack
sprayers,
and
turfguns.
Homeowners
can
also
use
other
types
of
application
equipment
including
trigger
sprayers,
hose
end
sprayers,
and
ready
to
use
dust
packaging.
Information
on
uses
and
application
rates
used
in
the
risk
assessment
was
provided
by
the
registrant,
Aventis
Crop
Science,
at
a
SMART
meeting
on
September
21,
1998
and
from
a
review
of
current
labels.
The
Agency's
Biological
and
Economic
Analysis
Division
has
also
concurred
with
the
use
patterns
which
serve
as
the
basis
for
this
assessment.
Carbaryl
also
has
more
specialized
uses
that
can
lead
to
exposures
in
the
general
population
such
as
an
adulticide
for
mosquito
control
and
for
Ghost
and
Mud
shrimp
control
in
oyster
beds
in
Washington
State.
These
use
patterns
were
also
considered
in
this
assessment.
Hazard
Characterization:
Carbaryl
is
a
carbamate
insecticide
where
the
mode
of
toxic
action
is
through
cholinesterase
inhibition
(ChEI).
In
most
of
the
toxicology
studies
in
which
ChEI
activity
was
measured,
it
was
the
endpoint
used
for
setting
the
No
Observed
Adverse
Effect
Level
(NOAEL)
for
risk
assessment,
the
dose
at
which
no
adverse
effects
were
observed.
There
was
one
exception;
for
chronic
duration
exposures,
a
NOAEL
could
not
be
defined
in
the
toxicology
study
deemed
most
appropriate
(i.
e.,
chronic
dog
toxicity)
so
a
Lowest
Observed
Adverse
Effect
Level
(LOAEL),
the
dose
at
which
the
first
adverse
6
effects
were
observed,
was
used
for
risk
assessment
purposes.
Carbaryl
is
relatively
acutely
toxic
by
the
oral
route
(Toxicity
Category
II)
but
has
relatively
low
acute
toxicity
by
the
dermal
and
inhalation
routes.
It
is
not
a
dermal
or
eye
irritant
or
a
dermal
sensitizer;
however,
there
are
reports
of
dermal
irritation
and
dermal
manifestations
of
an
allergic
response
in
humans
exposed
to
carbaryl.
The
Agency
is
required
by
the
Food
Quality
Protection
Act
to
consider
the
special
sensitivities
of
various
susceptible
populations
such
as
infants
and
children.
Current
Agency
policy
retains
the
factor
using
criteria
based
on
exposure
and
toxicity
considerations.
For
carbaryl,
a
traditional
factor
of
3
was
applied
only
to
chronic
duration
exposures
to
account
for
the
lack
of
a
NOAEL
in
the
selected
chronic
dog
toxicity
study
(i.
e.,
the
use
of
a
LOAEL).
The
Agency
decided
that
the
special
FQPA
Safety
Factor
should
be
reduced
to
1
and
that
this
was
adequate
to
protect
susceptible
populations
because
there
are
no
residual
uncertainties
in
the
exposure
databases,
the
toxicology
database
is
complete,
and
the
endpoint
and
NOAELs
for
risk
assessment
were
well
defined.
Dietary
exposures
were
calculated
using
FDA
and
PDP
monitoring
data,
a
carbamate
market
basket
survey,
and
percent
crop
treated
information.
Residential
exposures
were
calculated
using
a
number
of
carbaryl
specific
studies.
In
the
toxicology
database,
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
in
rat
or
rabbit
fetuses
following
in
utero
exposure
in
the
standard
developmental
studies
was
observed.
There
was
a
low
level
of
concern
for
evidence
of
susceptibility
seen
in
the
developmental
neurotoxicity
study,
and
there
was
evidence
of
increased
susceptibility
in
offspring
in
the
2
generation
reproduction
study.
However,
the
Agency
believes
that
the
acute
and
chronic
RfDs
would
be
protective
of
these
effects
so
the
special
FQPA
safety
factor
was
reduced
to
1.
Carbaryl
has
been
classified
as
a
Group
C
possible
human
carcinogen
based
on
an
increased
incidence
of
hemangiosarcomas
and
combined
hemangiomas/
hemangiosarcomas
in
CD
1
mice
at
100
ppm
and
above
(15
and
18
mg/
kg/
day
for
males
and
females,
respectively).
Mechanistic
metabolism
studies
and
a
study
in
heterozygous
p53
deficient
mice
were
considered
inadequate
to
demonstrate
a
mode
of
action
for
the
vascular
tumors.
Therefore,
a
linear
low
dose
extrapolation
approach
was
used
for
risk
assessment;
the
Q1*
is
8.75
x
10
4
(mg/
kg/
day)
1
based
on
the
mouse
vascular
tumors
according
to
the
February
2002
Cancer
Assessment
Review
Committee
(CARC)
report.
Also,
CARC
concluded
that
there
is
a
concern
for
mutagenicity
because
carbaryl
has
been
observed
to
be
clastogenic
in
vitro.
However,
this
concern
is
lessened
because
of
a
lack
of
effects
observed
in
vivo
(i.
e.,
micronuclei
induction
and
chromosome
aberration
studies
were
negative).
Endpoints
for
acute
and
chronic
dietary
exposure
risk
assessments
were
selected
by
the
HED
Hazard
Identification
Assessment
Review
Committee
(HIARC).
The
toxicity
endpoints
selected
for
risk
assessment
are
neurotoxic
effects
associated
with
the
inhibition
of
ChEI.
The
dose
level
used
for
the
acute
dietary
risk
assessment
was
a
NOAEL
which
was
defined
in
a
developmental
neurotoxicity
study
conducted
with
rats
(1
mg/
kg/
day).
The
dose
level
used
for
the
chronic
dietary
risk
assessment
was
a
LOAEL
which
was
defined
in
a
chronic
dog
feeding
study
(3.1
mg/
kg/
day).
Because
a
NOAEL
could
not
be
defined
in
the
chronic
study,
an
additional
factor
of
3x
was
added
to
the
customary
100x
factor
(i.
e.,
10x
for
extrapolation
from
animal
studies
to
humans
and
10x
for
intraspecies
variation
between
the
test
animals
and
humans)
to
account
for
the
uncertainty
associated
with
a
lack
of
a
NOAEL.
The
acute
and
chronic
reference
doses
(RfD)
were
0.01
mg/
kg/
day
(i.
e.,
dose/
100
for
acute
and
dose/
300
for
chronic).
The
Population
Adjusted
Dose
(PAD)
is
a
modification
of
the
acute
or
chronic
RfD
to
7
accommodate
the
FQPA
safety
factor
and
is
calculated
by
dividing
the
RfD
by
the
FQPA
safety
factor.
The
PADs
are
the
values
used
for
the
acute
and
chronic
dietary
risk
calculations.
The
Special
FQPA
Safety
Factor
was
reduced
to
1
as
described
above.
Therefore,
the
aPAD
and
cPAD
(i.
e.,
PAD
values
for
acute
and
chronic
dietary
exposures,
respectively)
are
both
0.01
mg/
kg/
day.
There
are
many
potential
ways
people
can
be
exposed
to
carbaryl
in
occupational
and
residential
settings.
The
Agency
considers
exposures
for
those
involved
in
the
application
of
carbaryl
(i.
e.,
handlers)
and
those
who
can
come
into
contact
with
carbaryl
residues
after
application
(i.
e.,
reentry
or
postapplication).
Both
cancer
and
non
cancer
risk
assessments
were
conducted
for
residential
handlers
and
for
people
in
the
general
population
who
might
be
exposed
postapplication
from
lawn,
garden,
or
pet
uses
of
carbaryl
or
from
more
specialized
uses
such
as
mosquito
adulticide
applications
and
uses
on
oyster
beds
in
Washington
state.
Similarly,
both
handler
and
postapplication
risks
were
calculated
for
those
people
who
could
be
exposed
as
part
of
their
jobs
such
as
a
grower
treating
their
crop
or
someone
harvesting
fruit.
Endpoints
for
occupational
and
residential
exposures
from
various
routes
(i.
e.,
dermal,
inhalation,
and
incidental
oral)
and
differing
durations
(i.
e.,
short
term,
intermediate
term,
and
chronic)
were
selected
by
the
HIARC.
Based
on
current
policy,
short
term
exposure
was
defined
as
1
to
30
days,
intermediate
term
exposures
as
30
days
to
several
months,
and
chronic
exposures
as
several
months
to
a
lifetime.
[Note:
Not
all
routes
and
durations
are
applicable
to
each
population.]
The
toxicity
endpoints
selected
for
these
carbaryl
risk
assessments
are
again
based
on
neurotoxic
effects
associated
with
the
inhibition
of
ChEI.
The
short
and
intermediate
term
dermal
risk
assessments
for
carbaryl
are
based
on
NOAEL
of
20
mg/
kg/
day
defined
in
a
dermal
toxicity
study
in
rats
using
technical
material
where
decreases
in
red
blood
cell
cholinesterase
in
males
and
females
and
brain
cholinesterase
in
males
were
observed.
The
short
term
inhalation
and
nondietary
ingestion
risk
assessments
for
carbaryl
are
based
on
a
NOAEL
of
1
mg/
kg/
day
which
was
defined
in
a
developmental
neurotoxicity
study
in
rats
where
alterations
in
FOB
measurements
and
cholinesterase
inhibition
(plasma,
whole
blood,
and
brain)
were
observed.
The
intermediate
term
inhalation
and
nondietary
ingestion
risk
assessments
are
based
on
a
NOAEL
of
1
mg/
kg/
day
that
was
defined
in
a
subchronic
neurotoxicity
study
in
rats.
The
chronic
risk
assessments,
regardless
of
how
exposures
occur
(e.
g.,
skin
or
inhaled)
are
based
on
a
LOAEL
of
3.1
mg/
kg/
day
that
was
defined
in
a
1
year
dog
feeding
study.
In
some
assessments,
a
dermal
absorption
factor
is
required.
A
rat
dermal
absorption
study
using
radiolabeled
14
C
carbaryl
was
used
to
define
a
factor
of
12.7
percent;
this
value
was
used
to
calculate
the
oral
equivalent
dermal
dose
for
noncancer
chronic
duration
exposures
and
for
the
calculation
of
cancer
risks.
No
inhalation
toxicity
studies
were
available
for
risk
assessment
purposes
so
a
route
to
route
extrapolation
was
used
to
address
risks
from
inhalation
exposures.
No
inhalation
absorption
study
was
conducted;
therefore,
a
100
percent
inhalation
absorption
factor
has
been
used
to
convert
all
inhalation
exposures
to
an
oral
equivalent
inhalation
dose.
Dietary
Risk
Estimates:
Potential
dietary
exposure
to
carbaryl
occurs
through
food
and
water.
Tolerances
for
residues
of
carbaryl
are
currently
expressed
in
terms
of
carbaryl
and
its
hydrolysis
product,
1
naphthol
(calculated
as
carbaryl)
for
most
raw
agricultural
commodities.
However,
HED
is
recommending
that
carbaryl
per
se
be
regulated
in
plants.
In
livestock
commodities,
carbaryl;
5,6
dihydro
5,6
dihydroxy
carbaryl;
and
1
At
the
present
time,
information
from
the
industry
sponsored
Carbamate
Market
Basket
Survey
has
been
approved
for
use
in
dietary
risk
assessments
with
appropriate
characterization
of
uncertainties
associated
with
the
conduct
of
the
study.
The
primary
concern
was
rubbing
sampled
commodities
during
the
rinsing
process
except
for
broccoli
and
tomato
because
this
created
a
potential
for
residue
loss
from
the
mechanical
action
associated
with
rubbing.
A
separate
assessment
was
also
completed
using
other
sources
of
high
quality
residue
data
(e.
g.,
PDP)
for
comparative
purposes
to
more
completely
inform
the
risk
management
process.
8
5
methoxy
6
hydroxy
carbaryl
and
all
residues
which
can
be
hydrolyzed
to
carbaryl,
5,6
dihydro
5,6
dihydroxy
carbaryl,
or
5
methoxy
6
hydroxy
carbaryl
under
acidic
conditions
should
be
included
in
the
tolerance
expression
and
risk
assessment
for
all
endpoints
of
dietary
concern.
Once
the
tolerances
for
plants
are
revised,
they
will
be
compatible
with
Codex
MRLs
except
for
livestock
commodities.
A
Tier
3/
4
dietary
risk
assessment,
which
is
the
most
highly
refined
assessment
possible
at
this
time,
was
conducted.
Both
acute
and
chronic
dietary
risk
assessments
were
conducted.
Dietary
exposure
was
determined,
considering
the
level
of
carbaryl
residue
on
food
commodities
and
their
potential
consumption
by
multiple
subpopulations.
Dietary
risk
was
then
calculated
by
comparing
dietary
exposure
to
the
acute
or
chronic
PADs.
Data
on
anticipated
carbaryl
residues
were
determined
based
mainly
on
USDA
Pesticide
Data
Program
(PDP)
and
Food
and
Drug
Administration
(FDA)
monitoring
data.
Field
trial
data
were
used
for
certain
commodities.
In
addition,
separate
acute
assessments
were
conducted
incorporating
the
results
of
the
Carbamate
Market
Basket
Survey
(CMBS).
1
The
percentage
of
the
crop
treated
(estimated
maximum
percentage
and
weighted
average
percentage
for
the
acute
and
chronic
analyses,
respectively)
was
also
considered.
Food
consumption
data
were
from
2
of
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(CSFII)
which
ranged
from
1989
to
1992
and
from
1994
to
1998.
The
1994
to
1998
data
were
included
based
on
comments
from
the
registrant,
Aventis
Crop
Science,
for
comparative
purposes
(1989
to
1992
are
normally
used
for
risk
assessment).
In
these
surveys,
3
day
mean
consumption
and
single
day
consumption
information
were
recorded
for
22
demographic
and
socio
economic
subpopulations,
including
infants,
children,
and
nursing
women.
Dietary
risk
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(DEEM™),
which
incorporates
exposure
and
consumption
data
to
calculate
risk
as
a
percentage
of
the
PAD.
Values
greater
than
100
percent
of
the
PAD
exceed
HED's
level
of
concern.
Estimated
acute
dietary
exposure
for
carbaryl
at
the
99.9
th
percentile
using
the
1989
to
1992
CFSII
data
exceeds
HED's
level
of
concern
for
some
population
subgroups
when
CMBS
data
are
not
used
and
are
not
of
concern
when
the
CMBS
are
incorporated.
The
results
of
the
acute
dietary
assessment
when
CMBS
data
have
not
been
used
indicate
risks
are
greater
than
100
percent
of
the
aPAD
for
all
infants
(<
1
year
old)
and
children
(1
6
years
old)
at
the
99.9
th
percentile
of
exposure
(133
%
and
110%
of
aPAD,
respectively).
When
CMBS
data
were
incorporated,
the
highest
exposed
subpopulation
was
children
(1
6
years
old)
at
75
percent
of
the
aPAD.
A
sensitivity
analysis
was
completed
by
the
Agency
(not
using
the
CMBS)
to
evaluate
the
impacts
of
eliminating
apples
or
peaches
from
the
analysis
and
eliminating
commodities
with
no
detectable
residues.
Eliminating
peaches
appears
to
have
the
most
impact
as
all
infants
in
this
analysis
consume
72
percent
of
the
aPAD
but
children
(1
6
years
old)
still
consume
just
over
100
percent
of
the
aPAD
(i.
e.,
102
percent).
One
comment
from
Aventis
Crop
Science
was
that
1994
to
1998
CFSII
food
consumption
data
should
be
used
rather
than
1989
to
1992
data.
Results
for
most
subpopulations
were
actually
slightly
worse
(i.
e.,
generally,
5
to
10
percent
9
more
of
the
aPAD
was
consumed)
if
the
1994
to
1998
CFSII
data
were
used.
Estimated
chronic
dietary
risks
for
all
population
subgroups
are
not
of
concern.
Estimated
chronic
dietary
exposures
for
all
population
subgroups
consumed
<1
percent
of
the
cPAD.
The
CMBS
data
were
not
used
in
this
analysis
because
risks
are
low
and
CMBS
is
single
serving
data.
The
cancer
dietary
exposure
assessment
was
conducted
using
the
Q
1*
approach
(i.
e.,
linear,
low
dose
extrapolation).
Dietary
exposure
is
determined
from
consumption
and
residue
data,
as
was
done
for
the
acute
and
chronic
dietary
assessments.
The
food
exposure
is
then
multiplied
by
the
Q
1*
(8.75
x
10
4
)
(mg/
kg/
day)
1
for
carbaryl
to
determine
the
increased
risk
of
cancer
from
consuming
carbaryl
residues
in
food
over
a
lifetime
(70
years).
Risks
estimates
above
1
x
10
6
are
of
concern.
Results
indicate
a
maximum
lifetime
risk
of
2.8
X
10
8
for
the
general
US
population.
Concentrations
in
Water:
Monitoring
data
for
carbaryl
residues
in
ground
and
surface
water
are
available,
but
they
are
of
limited
utility
in
developing
estimated
environmental
concentrations
(EECs)
for
the
aggregate
dietary
(food
and
water)
risk
assessment.
Therefore,
computer
modeling
was
used
to
estimate
surface
(PRZM
3.12
and
EXAMS
2.97.7)
and
ground
(SCI
GROW)
water
concentrations
expected
from
normal
agricultural
use.
These
model
estimates
were
compared
to
drinking
water
levels
of
concern
(DWLOCs),
the
theoretical
concentration
of
pesticide
in
drinking
water
that
would
be
an
acceptable
upper
limit
in
light
of
the
aggregate
exposure
to
that
pesticide
from
other
sources
(food
and
residential
use).
The
maximum
calculated
acute
and
chronic
surface
water
EECs
(494
ppb
and
28
ppb,
respectively)
resulted
from
use
on
citrus
in
Florida.
In
Florida,
the
majority
of
drinking
water
is
derived
from
groundwater
(>
90%)
so
high
surface
water
concentrations
do
not
necessarily
indicate
high
exposure.
As
a
result,
both
Florida
and
the
results
for
Oregon
apples
(the
next
highest
EECs)
have
been
considered
in
the
aggregate
assessment
(144
and
9
ppb
for
acute
and
chronic,
respectively).
Groundwater
EECs
for
the
acute
and
chronic
assessments
were
both
0.8
ppb
as
calculated
with
SCI
GROW.
Use
of
Consumer
Products
(Residential
Handlers):
The
noncancer
risks
of
short
term
dermal
and
inhalation
exposure
to
residential
handlers
were
calculated
using
Margins
of
Exposure
(MOEs)
in
which
the
doses
were
selected
from
the
21
day
dermal
toxicology
study
using
technical
material
and
the
developmental
neurotoxicity
study,
respectively.
The
target
(acceptable)
MOE
for
residential
short
term
risk
assessments
is
100
based
on
the
customary
100x
uncertainty
factor
(i.
e.,
10x
for
inter
and
10x
for
intra
species)
and
the
FQPA
Safety
Factor
of
1.
Calculated
MOEs
that
equal
or
exceed
the
target
MOE
of
100
are
not
of
concern.
Combined
(dermal
and
inhalation)
risks
were
calculated
for
17
scenarios
(i.
e.,
52
site/
area/
rate
combinations
within
those
scenarios)
considered
representative
of
the
residential
uses,
application
rates
and
application
equipment
on
carbaryl
labels.
For
residential
handlers,
MOEs
associated
with
most
(40
of
52
considered)
are
10
generally
not
of
concern
because
they
exceed
the
Agency's
target
MOEs
for
noncancer
risk
assessments
(i.
e.,
MOE
=
100).
The
scenarios
of
concern
involve
the
use
of
dusts
(in
gardens
and
on
pets)
and
for
some
liquid
sprays
on
gardens.
The
risk
of
cancer
in
residential
handlers
was
calculated
considering
one
application
of
carbaryl
per
year
for
50
years.
The
annual
frequency
for
use
was
reported
to
be
1
to
2
times
per
year
(60
th
percentile)
and
5
times
per
year
(84
th
percentile)
by
the
registrant,
the
Aventis
Crop
Science,
at
the
SMART
meeting
held
with
the
Agency.
Risks
were
calculated
by
multiplying
the
Lifetime
Average
Daily
Dose
(LADD),
which
represents
dermal
and
inhalation
exposure
amortized
over
a
lifetime,
by
the
Q1*.
The
risk
considered
acceptable
is
1
x
10
6
,
which
means
that
an
individual
receiving
a
lifetime
exposure
to
a
pesticide
increases
their
chance
of
developing
cancer
by
one
in
a
million.
Based
on
a
single
day
of
exposure,
cancer
risks
for
most
scenarios
are
in
the
10
8
to
10
10
range
although
there
is
one
scenario
where
the
risk
exceeds
1x10
6
(dusting
dogs)
even
for
a
single
day
of
use.
Cancer
risks
have
also
been
calculated
using
another
approach
where
the
number
of
days
per
year
of
exposure
required
to
exceed
a
risk
of
1x10
6
has
been
defined.
There
are
5
scenarios
where
the
allowable
days
per
year
of
exposure
is
less
than
or
equal
to
5
which
should
be
considered
in
conjunction
with
the
use/
usage
data
from
Aventis
Crop
Science
that
indicates
5
uses
per
year
is
the
84
th
percentile.
In
all
cases,
cancer
risk
estimates
require
less
restrictive
risk
mitigation
measures
than
do
the
corresponding
results
for
noncancer
concerns
(i.
e.,
noncancer
risks
appear
to
be
driving
the
need
for
risk
mitigation).
Residential
Postapplication
Exposures:
HED
considered
a
number
of
residential
postapplication
exposure
scenarios
for
toddlers,
youthaged
children
and
adults.
Short
term
and
intermediate
term
risks
from
declining
residues
were
calculated
for
multiple
scenarios,
including
exposures
to
treated
lawns
(toddlers
and
adults),
golf
courses
(adults),
gardens
(adults
and
youth
aged
children)
and
pets
(toddlers).
Exposures
from
more
limited
uses
such
as
a
mosquito
adulticide
and
for
use
in
oyster
beds
were
also
considered.
Short
and
intermediate
term
dermal
risks
were
calculated
using
the
NOAEL
from
the
21
day
dermal
toxicity
study
(i.
e.,
20
mg/
kg/
day).
Risks
from
short
and
intermediate
term
nondietary
ingestion
(e.
g.,
mouthing
behaviors)
were
calculated
using
NOAELs
from
the
developmental
neurotoxicity
study
in
rats
and
the
subchronic
neurotoxicity
study
in
rats
where
the
NOAELs
both
happen
to
be
1
mg/
kg/
day.
The
target
MOE
is
also
100
for
all
scenarios
considered.
MOEs
were
calculated
over
the
amount
of
time
it
took
residues
to
dissipate
or
out
to
a
30
day
interval
whichever
applied
depending
upon
the
data.
Short
term
MOEs
were
calculated
based
on
the
residue
concentrations
for
each
day
while
intermediate
term
risks
were
calculated
using
a
30
day
average.
The
Agency
has
short
term
risk
concerns
for
exposures
to
adults
doing
heavy
yardwork,
for
toddlers
playing
on
treated
lawns,
and
for
toddlers
that
have
contact
with
treated
pets.
Activities
associated
with
home
gardening
(e.
g.,
harvesting)
and
golfing
for
adults,
home
gardening
for
youth
aged
children
or
any
age
or
activity
considered
in
the
adulticide
mosquito
control
or
oyster
assessment
do
not
have
risk
concerns
even
on
the
day
of
application
(i.
e.,
MOEs
$
100
on
the
day
of
application).
For
adults,
the
MOEs
for
heavy
yardwork
do
not
meet
or
exceed
risk
targets
(i.
e.,
MOE
$
100)
up
to
5
days
after
application.
For
toddlers,
the
Agency
has
concerns
for
pet
treatments
and
also
for
lawn
uses.
In
fact,
pet
uses
never
reach
acceptable
levels
even
30
days
after
application
and
not
until
18
days
at
the
maximum
application
rate
considered
on
turf.
Toddler
MOEs
from
pet
and
turf
uses
represent
total
exposures
from
multiple
pathways.
For
the
pet
uses,
dermal
and
11
hand
to
mouth
exposures
essentially
both
equally
contribute
to
the
overall
estimate.
For
the
turf
uses,
dermal
and
hand
to
mouth
exposures
are
also
the
key
contributors
to
the
overall
estimates.
The
Agency
does
not
have
intermediate
term
risk
concerns
for
adults
and
youth
aged
children
for
any
of
the
uses
considered
including
lawncare,
home
gardens,
golfing,
and
any
aspect
of
adulticide
mosquito
control
or
uses
in
oyster
beds.
In
contrast,
the
Agency
does
have
intermediate
term
risk
concerns
for
all
toddler
exposure
scenarios
considered
(i.
e.,
pet
treatments
and
lawncare
uses).
As
with
the
short
term
MOEs,
pet
and
turf
uses
represent
total
exposures
where
the
significant
contributions
to
overall
exposures
are
again
made
equally
from
the
dermal
and
hand
to
mouth
exposure
pathways.
Ingestion
of
carbaryl
granules
is
also
a
potential
source
of
exposure
because
children
can
eat
them
if
they
are
found
in
treated
lawns
or
gardens.
This
scenario
is
considered
episodic
by
the
Agency
and
is
generally
not
recommended
as
a
basis
for
risk
management
decisions.
For
illustrative
purposes,
if
one
considers
a
2
percent
formulation
and
the
density
of
soil
(0.67
mL/
gram,
many
granulars
are
claybased),
only
0.005
mL
of
formulation
would
need
to
be
ingested
to
have
a
risk
concern
(i.
e.,
7.5
mg
*
1g/
1000mg
*
0.67
mL/
gram).
[Note:
This
volume
is
orders
of
magnitude
less
than
a
teaspoon
of
granular
formulation
(i.
e.,
0.1%
of
a
teaspoon
where
a
tsp.
=
5
mL).]
Use
in
Tobacco:
In
addition
to
the
routine
residential
risk
assessment,
HED
calculated
the
risks
of
carbaryl
exposure
in
tobacco
because
a
pyrolysis
study
was
submitted
by
the
registrant
that
quantified
residues
of
carbaryl
at
a
level
of
44.58
ppm
in
tobacco
smoke
(side
stream
and
main
stream
combined).
Since
this
is
a
composited
sample
of
main
stream
and
side
stream
smoke,
it
greatly
exaggerates
the
actual
exposure
to
the
smoker,
whose
primary
route
of
exposure
is
via
main
stream
smoke.
HED
further
assumed
that
100
percent
inhaled
is
absorbed
(i.
e.,
that
none
of
the
residue
is
exhaled
along
with
the
smoke).
The
MOE
for
consuming
15
cigarettes
per
day
is
104
even
with
the
conservative
basis
of
the
assessment.
Aggregate
Risks
and
DWLOCs:
The
Food
Quality
Protection
Act
requires
that
the
Agency
consider
exposures
from
different
sources
(i.
e.,
food
water,
and
residential)
that
results
in
an
aggregate
risk
for
each
chemical.
Aggregate
risks
are
calculated
by
considering
food
or
food
and
residential
(depends
upon
the
specific
scenario),
subtracting
these
from
the
allowable
exposure
limit,
and,
if
the
exposure
limit
has
not
been
exceeded,
then
calculating
Drinking
Water
Levels
of
Concern
(DWLOCs)
to
compare
to
surface
or
groundwater
Estimated
Environmental
Concentrations
(EECs).
In
many
residential
scenarios,
MOEs
exceed
the
Agency's
risk
targets
making
the
calculation
of
DWLOCs
and
aggregate
risks
for
those
scenarios
inappropriate
because
the
allowable
exposure
limits
have
already
been
exceeded.
Additionally,
acute
dietary
risks
were
also
exceeded
for
infants
and
children
(1
to
6
years
old)
at
the
99.9
th
percentile
when
the
Carbamate
Market
Basket
Survey
(CMBS)
was
not
considered
in
the
assessment
(133
%
of
aPAD).
However,
the
risk
picture
could
substantively
change
if
residential
risks
are
refined
based
on
updated
use
information
from
the
carbaryl
use
survey
yet
to
be
submitted
to
the
Agency,
and
the
Agency
uses
the
CMBS
data
even
with
the
caveats
associated
with
that
study.
Keeping
this
in
mind,
the
Agency
completed
DWLOC
12
and
aggregate
risk
calculations
for
illustrative
purposes
using
a
number
of
representative
exposure
scenarios
where
the
residential
and
dietary
risk
estimates
did
not
already
exceed
the
Agency's
level
of
concern.
For
example,
an
acute
assessment
with
CMBS
data
and
short
term
assessments
where
residential
handler
risks
weren't
already
of
concern
were
completed.
The
acute
aggregate
assessment
indicates
that
even
with
the
use
of
the
CMBS,
aggregate
risks
when
surface
water
is
the
source
of
drinking
water,
are
still
of
concern
for
all
infants,
children
(1
to
6
years
old)
and
children
(7
to
12
years
old)
regardless
of
whether
or
not
Florida
citrus
or
Oregon
apple
EECs
are
used.
If
Florida
citrus
surface
water
EECs
are
solely
considered,
aggregate
risks
are
of
concern
for
all
subpopulations.
[Note:
For
characterization
of
the
EECs,
surface
water
EECs
for
Florida
citrus
exceed
exposure
limits
alone
without
even
considering
corresponding
food
intakes
for
all
populations.
Additionally,
the
surface
water
EECs
for
Oregon
apples
alone
also
exceed
exposure
limits,
even
without
including
food
intakes,
for
infants
and
children.]
Acute
aggregate
risks
for
all
subpopulations
are
not
of
concern
if
groundwater
is
the
source
of
drinking
water.
Chronic
aggregate
risks
were
not
of
concern
for
any
subpopulation
regardless
of
the
source
of
drinking
water,
even
considering
the
Florida
surface
water
EECs.
In
the
short
term
assessment,
the
Agency
selected
representative
scenarios
where
residential
risks
alone
were
not
of
concern
including
mosquito
control,
oyster
harvesting,
golfing,
garden
harvest,
and
several
handler
scenarios
(handlers
all
at
average
rates,
max
rate
scenarios
were
of
concern
for
residential
exposures
alone).
If
surface
water
EECs
based
on
Oregon
apples
or
groundwater
EECs
from
SciGrow
are
considered,
aggregate
risks
are
not
of
concern
for
the
selected
scenarios.
If
EECs
from
Florida
citrus
are
considered,
aggregate
risks
are
not
of
concern
for
the
selected
scenarios
except
for
application
of
dusts
to
gardens.
Separate
intermediate
term
aggregate
risk
and
DWLOC
calculations
were
not
completed
for
carbaryl
because
the
short
term
aggregate
risk
estimates
essentially
present
the
same
results
since
the
hazard
inputs
are
numerically
identical.
The
only
major
differences
would
be
the
postapplication
results
where,
instead
of
a
single
day
exposure
estimate,
the
exposures
represent
a
30
day
average
(i.
e.,
risks
would
be
accordingly
lower
since
an
average
rather
than
a
single
high
end
day
was
considered).
Aggregate
cancer
risks
were
not
of
concern
for
any
subpopulation
regardless
of
the
source
of
drinking
water,
even
considering
the
Florida
surface
water
EECs.
Cumulative
Risks:
Carbaryl
is
a
member
of
the
carbamate
class
of
pesticides.
This
class
also
includes
the
aldicarb,
methomyl
and
oxamyl
among
others.
HED
did
not
perform
a
cumulative
risk
assessment
as
part
of
this
reregistration
review
for
carbaryl
because
HED
has
not
yet
initiated
a
review
to
determine
if
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
carbaryl.
For
purposes
of
this
reregistration
decision,
EPA
has
assumed
that
carbaryl
does
not
have
a
common
mechanism
of
toxicity
with
other
substances.
13
Occupational
Handlers:
There
is
significant
potential
for
exposure
to
carbaryl
users
in
a
variety
of
agricultural
and
commercial
settings.
Tasks
associated
with
occupational
carbaryl
use
include
mixing,
loading
and
applying
the
chemical
or
guiding
aerial
applications
(flaggers).
All
these
activities
are
collectively
referred
to
as
handler
tasks.
A
total
of
28
scenarios
were
considered
representative
of
the
range
of
handler
activities,
crops
or
acres
treated
and
equipment
used.
The
risks
from
short
and
intermediateterm
dermal
exposures
and
short
and
intermediate
term
inhalation
exposures
in
these
scenarios
were
calculated
and
then
added
together
to
obtain
overall
risk
estimates
at
varying
levels
of
personal
protection.
The
target
MOEs
were
100
for
short
term
and
intermediate
term
exposures.
[Note:
Does
not
include
FQPA
Safety
Factors
as
they
are
not
applicable
to
occupational
exposures.]
Risks
from
longterm
(chronic)
exposures
were
also
calculated
for
a
limited
number
of
scenarios
in
the
ornamental/
greenhouse
industry.
The
short
and
intermediate
term
risk
assessments
were
conducted,
as
described
above.
The
long
term
risk
assessment
for
carbaryl
was
based
on
a
1
year
dog
feeding
study
where
effects
(ChEI)
were
observed
at
3.1
mg/
kg/
day
(LOAEL).
The
target
MOE
was
300
(customary
100x
plus
3x
for
use
of
LOAEL).
Risks
were
calculated
assuming
one
of
eight
possible
levels
of
personal
protection
equipment,
ranging
from
a
baseline
of
typical
work
clothing
(long
sleeved
shirt
and
long
pants,
no
respiratory
protection
and
no
chemical
resistant
gloves)
to
engineering
controls,
such
as
a
closed
cab
or
closed
loading
system.
Current
carbaryl
labels
typically
require
that
handlers
wear
long
pants,
long
sleeved
shirts,
and
gloves
but
do
not
require
respirators.
For
most
scenarios,
the
noncancer
risks
for
this
personal
protection
ensemble
do
not
meet
Agency
risk
requirements
and
additional
levels
of
personal
protection
are
required
to
achieve
Agency
risk
targets.
In
fact,
in
many
cases
engineering
controls
such
as
closed
loading
systems
or
closed
cab
tractors
are
needed.
The
Agency
does
have
risk
concerns
over
the
use
of
carbaryl
in
some
agricultural
and
other
occupational
settings
regardless
of
the
level
of
personal
protection
used
(i.
e.,
MOEs
at
any
level
of
personal
protection
are
<targets).
As
would
be
expected,
these
scenarios
with
the
highest
associated
risk
also
have
high
daily
chemical
use
amounts
based
on
application
rates
or
high
acreages
treated
or
the
exposures
for
the
scenarios
in
question
are
relatively
high.
Generally,
the
areas
that
appear
to
be
problematic
include:
large
acreage
aerial
and
chemigation
applications
in
agriculture
or
for
wide
area
treatments
such
as
mosquito
control;
airblast
applications
at
higher
rates;
pet
grooming;
and
the
use
of
certain
handheld
equipment
for
applications
to
turf
or
gardens
(e.
g.,
bellygrinder).
This
general
trend
was
essentially
the
same
for
exposures
of
any
duration.
Several
data
gaps
were
also
identified
in
many
different
use
areas
that
include:
dust
use
for
animal
grooming
and
in
agriculture;
various
specialized
hand
equipment
application
methods
(e.
g.,
powered
backpack,
power
hand
fogger,
and
tree
injection);
and
nursery
operations
such
as
seedling
dips.
The
risk
of
cancer
for
occupational
handlers
was
calculated
for
two
populations,
private
growers
(10
applications
per
year)
and
commercial
applicators
(30
applications
per
year),
using
the
same
28
scenarios.
According
to
Agency
policy,
acceptable
cancer
risks
for
occupational
exposure
to
pesticides
can
vary
from
1x10
4
to
1x10
6
,
depending
on
the
course
of
action
taken
by
the
Agency
as
outlined
in
the
2
The
Agency
has
defined
a
range
of
acceptable
cancer
risks
based
on
a
policy
memorandum
dated
August
14,
1996,
by
Office
of
Pesticide
Programs
Director
Dan
Barolo.
This
memo
refers
to
a
predetermined
quantified
"level
of
concern"
for
occupational
carcinogenic
risk.
Occupational
carcinogenic
risks
that
are
1
x
10
6
or
lower
require
no
risk
management
action.
For
those
chemicals
subject
to
reregistration,
the
Agency
is
to
carefully
examine
uses
with
estimated
risks
in
the
10
6
to
10
4
range
to
seek
ways
of
cost
effectively
reducing
risks.
If
carcinogenic
risks
are
in
this
range
for
occupational
handlers,
increased
levels
of
personal
protection
are
warranted
as
is
commonly
applied
with
noncancer
risk
estimates
(e.
g.,
additional
PPE
or
engineering
controls).
Carcinogenic
risks
that
remain
above
1.0
x
10
4
at
the
highest
level
of
mitigation
appropriate
for
that
scenario
remain
a
concern.
14
the
subject
policy
2
.
Risks
for
corresponding
scenarios
based
on
cancer
concerns
were
generally
less
than
the
corresponding
noncancer
results
across
all
scenarios.
In
fact,
in
all
but
one
scenario,
cancer
risks
were
<1x10
4
at
current
carbaryl
label
requirements
of
single
layer
clothing,
gloves,
and
no
respirator
for
both
private
growers
and
commercial
applicators
(i.
e.,
mixing/
loading
wettable
powders
for
wide
area
aerial
applications).
Higher
levels
of
personal
protection
reduce
this
risk
to
<1x10
4
in
both
populations.
If
a
1x10
6
risk
level
is
specified
as
a
concern,
results
are
similar
in
that
risks
for
a
majority
of
scenarios
are
<1x10
6
at
current
label
requirements.
In
fact,
only
8
of
the
128
scenarios
considered
for
private
applicators
have
cancer
risks
>1x10
6
(and
less
than
1x10
4
)
even
with
the
most
protective
ensembles
of
protective
clothing
or
engineering
controls.
For
commercial
applicators,
results
indicate
that
risks
for
about
half
of
the
scenarios
considered
are
<1x10
6
at
current
label
requirements
and
that
only
21
of
the
128
scenarios
considered
have
cancer
risks
>1x10
6
(and
less
than
1x10
4
)
even
with
the
most
protective
ensembles
of
either
protective
clothing
or
engineering
controls.
Occupational
Postapplication
(Reentry
Workers):
Workers
can
be
exposed
to
carbaryl
residues
when
entering
previously
treated
areas
to
perform
certain
activities,
such
as
harvesting.
Current
label
requirements
specify
12
hour
Restricted
Entry
Intervals
(REIs)
while
Pre
Harvest
Intervals
(PHIs)
are
less
than
7
days
for
most
crops
with
some
as
long
as
28
days.
Non
cancer
risks
from
short
and
intermediate
term
dermal
postapplication
exposure
were
calculated
for
18
representative
crop
groupings
using
the
MOE
approach.
The
risks
from
long
term
dermal
exposures
were
calculated
for
only
a
limited
number
of
scenarios
in
the
greenhouse
and
floriculture
industries.
For
each
scenario,
the
risk
on
the
day
of
application
was
calculated,
along
with
the
time
required
to
reach
the
target
MOE,
allowing
for
dissipation
of
the
carbaryl
residues.
For
all
but
the
lowest
exposure
scenarios
in
some
crops,
MOEs
do
not
meet
or
exceed
target
MOEs
until
several
days
after
application.
If
short
term
risks
are
considered,
MOEs
meet
or
exceed
target
MOEs
generally
in
the
range
of
3
to
5
days
after
application
for
lower
to
medium
exposure
activities
and
from
8
to
12
days
after
application
in
most
higher
exposure
scenarios.
If
intermediate
term
risks
are
considered,
MOEs
are
not
of
concern
based
on
a
30
day
average
exposures
except
for
higher
level
exposures
such
as
harvesting
in
some
crops.
Chronic
exposures
are
of
concern
for
the
cut
flower
industry
but
not
for
other
general
greenhouse
and
nursery
production
activities
based
on
the
most
recent
data.
Cancer
risks
were
calculated
for
private
growers
and
professional
farmworkers
with
the
only
difference
being
the
annual
frequency
of
exposure
days.
Cancer
risks
for
private
growers
and
commercial
farmworkers
are
generally
in
the
10
8
to
10
6
range
on
the
day
of
application.
If
a
1x10
4
cancer
risk
is
the
target,
the
current
REI
would
be
adequate
for
all
scenarios
considered
in
the
15
assessment.
If
a
1x10
6
cancer
risk
is
used,
then
durations
longer
than
the
current
REI
should
be
considered
for
some
cases
which
are
not
considered
low
to
medium
exposures.
It
should
be
noted
that
the
cancer
risk
calculations
are
less
restrictive
than
noncancer
risk
estimates
for
the
same
scenarios
in
all
cases.
Many
mechanized
or
partially
mechanized
processes
are
possibly
associated
with
the
use
of
carbaryl
that
may
limit
or
eliminate
exposures
(e.
g.,
combines
for
grain
harvest).
Human
and
Domestic
Animal
Incidents:
HED
evaluated
reports
of
human
carbaryl
poisonings
and
adverse
reactions
associated
with
its
use
from
the
following
sources:
OPP
Incident
Data
System
(IDS);
Poison
Control
Centers'
Toxic
Exposure
Surveillance
System;
California
Department
of
Pesticide
Regulation;
the
National
Pesticide
Telecommunications
Network
(NPTN);
open
literature;
and
an
unpublished
study
submitted
by
the
registrant.
The
data
from
IDS
indicated
that
a
majority
of
cases
from
carbaryl
exposure
involved
dermal
reactions.
A
number
of
other
cases
involved
asthmatics
and
people
who
experienced
hives
and
other
allergic
type
reactions.
It
is
noted
that
the
dermal
sensitization
study
in
the
guinea
pig
was
negative.
Reports
of
allergic
type
reactions
in
humans
could
be
evidence
of
a
difference
in
species
sensitivity
or
could
be
attributable
to
inert
ingredients
in
the
marketed
formulations.
It
is
recommended
that
labels
for
products
should
advise
that
carbaryl
can
cause
sensitizing
effects
in
some
people.
According
to
California
data,
about
half
of
the
cases
involved
skin
and
eye
effects
in
handlers.
About
a
quarter
of
the
skin
reactions
were
due
to
workers
that
were
exposed
to
residues
on
crops.
Reports
from
the
literature
are
very
limited
but
tend
to
support
the
finding
that
carbaryl
has
irritant
properties.
The
Poison
Control
Center
cases
involving
non
occupational
adults
and
older
children
showed
an
increased
risk
in
five
of
the
six
measures
used
for
comparing
carbaryl
incidents
to
all
other
pesticides.
The
carbaryl
cases
were
almost
twice
as
likely
to
require
serious
health
care
(hospitalization
or
treatment
in
a
critical
care
unit)
and
were
two
and
a
half
times
more
likely
to
experience
major
medical
outcome
(life
threatening
effects
or
significant
residual
disability)
than
other
pesticides.
This
pattern
of
increased
risk
was
not
seen
among
occupational
reports
or
in
young
children.
This
may
mean
that
careless
handling
by
non
professionals
is
a
particular
hazard.
Five
case
report
studies
suggested
that
carbaryl
may
be
a
cause
of
chronic
neurological
or
psychological
problems.
Some
of
these
effects
appear
to
be
consistent
with
those
reported
from
organophosphate
poisoning.
However,
unlike
organophosphates,
no
controlled
studies
have
been
undertaken.
If
such
effects
occur
as
a
result
of
over
exposure
to
carbaryl,
they
appear
to
be
relatively
rare.
The
effects
reported
among
the
five
case
reports
are
too
inconsistent
to
draw
any
conclusions,
but
do
suggest
the
need
for
further
study.
The
epidemiologic
study
submitted
by
the
registrant
compared
mortality
rates
in
plant
workers
exposed
to
carbaryl
to
the
general
population.
HED
concluded
that
the
sample
of
workers
was
too
small
and
the
period
of
follow
up
too
short
to
permit
definitive
conclusions.
The
incident
reports
on
domestic
animals
in
IDS
were
evaluated.
Based
on
limited
data,
there
is
some
evidence
that
young
kittens
may
be
susceptible
to
adverse
reactions
to
carbaryl.
It
is
recommended
that
all
labels
for
carbaryl
products
used
on
cats
contain
the
age
restriction
stated
in
PR
Notice
96
6
(should
not
be
used
in
kittens
less
than
12
weeks
of
age).
16
Issues
For
Consideration:
There
are
population
based
monitoring
studies
in
the
published
literature
or
available
from
various
governmental
agencies
in
which
carbaryl
metabolites
are
measured
in
body
fluids
or
environmental
media.
For
example,
the
Agency's
Office
of
Research
and
Development,
along
with
other
Agencies,
has
funded
a
project
entitled
Pesticide
Exposure
in
Children
Living
in
Agricultural
Areas
along
the
United
States
Mexico
Border
Yuma
County,
Arizona.
Preliminary
results
of
this
study
indicate
that
carbaryl
residues
were
identified
in
the
dust
of
20
percent
of
the
152
houses
sampled
and
in
approximately
24
percent
in
25
samples
collected
in
6
schools
in
the
same
region.
With
regard
to
this
specific
example,
current
Agency
policy
is
not
to
use
house
dust
estimates
to
calculate
risks
because
of
a
lack
of
an
appropriate
exposure
model.
Also,
in
a
1995
study
conducted
by
the
Centers
For
Disease
Control
(Hill
et
al)
entitled
Pesticide
Residues
In
Urine
Of
Adults
Living
In
The
United
States:
Reference
Range
Concentrations,
1000
adults
were
monitored
via
urine
collection.
One
of
the
analytes
measured
in
that
study
(1
naphthol)
is
a
potential
metabolite
of
carbaryl
as
well
as
of
napthalene
and
napropamide
which
may
be
a
confounding
factor.
This
metabolite
(1
naphthol)
was
identified
in
86
percent
of
the
1000
adults
monitored.
Data
from
this
study
were
not
used
quantitatively
in
the
risk
assessment
for
carbaryl
because
of
the
uncertainties
associated
with
them,
such
as
the
exact
contribution
of
each
possible
compound
to
the
overall
levels
and
no
linked
exposure
information.
HED
instead
considered
them
a
qualitative
indicator
that
exposures
in
the
general
population
are
likely
to
occur.
As
more
data
become
available,
the
Agency
will
consider
the
information
in
an
effort
to
refine
the
assessment.
It
should
also
be
noted
that
Aventis
Crop
Science
has
completed
and
is
in
the
process
of
submitting
to
the
Agency
a
biomonitoring
study
of
individuals
in
residences
following
the
application
by
a
member
of
the
household
to
the
lawn
and
either
the
vegetable
garden
or
ornamental
flowers.
A
biomonitoring
study
of
field
workers
during
harvesting
and
hand
thinning
operations
in
apples
and
cherries
will
also
be
submitted
to
the
Agency.
Based
on
personal
communication
with
Aventis
Crop
Science
scientists,
preliminary
results
from
the
residential
biomonitoring
study
indicate
that
the
highest
percentiles
of
the
distribution
of
the
younger
children
in
the
homes
were
similar
to
those
predicted
in
the
Agency's
turf
risk
assessment
for
toddlers
that
are
intended
to
represent
the
higher
percentiles
of
the
exposure
distribution.
Preliminary
field
worker
results
also
appear
to
not
be
significantly
different
from
Agency
estimates.
The
database
for
carbaryl
contains
good
quality
studies
which
are
sufficient
for
conducting
a
risk
assessment
for
the
reregistration
of
the
chemical.
However,
certain
key
information,
which
would
help
refine
the
risk
assessment,
is
missing.
The
one
toxicology
data
gap
includes
a
90
day
inhalation
study
in
the
rat.
The
elimination
of
poultry
from
the
acute
and
chronic
dietary
risk
assessment
significantly
reduced
the
risks.
For
residential
postapplication
risk
assessments,
there
are
no
data
on
the
amount
of
residues
transferrable
from
treated
pets
to
humans.
Additional
residue
data
on
turf
would
also
help
refine
the
hand
to
mouth
and
object
to
mouth
toddler
exposures.
For
the
occupational
handler
risk
assessments,
several
handler
scenarios
lack
high
quality
data.
For
postapplication
workers,
additional
residue
dissipation
data
along
with
data
from
practices
not
well
represented
in
Agency
Policy
003
(Transfer
Coefficients)
are
needed
to
refine
the
assessment
(e.
g.,
partially
mechanized
practices
that
could
involve
contact).
17
O
O
N
H
CH
3
2.0
PHYSICAL/
CHEMICAL
PROPERTIES
CHARACTERIZATION
The
product
chemistry
chapter
was
prepared
by
Felicia
Fort
of
the
Health
Effects
Division
(November
14,
2000
DP
Barcode
240989).
All
information
below
is
excerpted
from
that
chapter
unless
specifically
noted.
Section
2.1:
Chemical
Structure
and
Identification
presents
the
nomenclature
and
structures
associated
with
carbaryl
and
its
metabolites.
Section
2.2:
Physical
Properties
of
Carbaryl
presents
information
about
the
properties
of
carbaryl.
2.1
Chemical
Structure
and
Identification
Chemical
Name:
1
naphthyl
methylcarbamate
Empirical
Formula:
C12H11NO2
Molecular
Weight:
201.2
CAS
Registry
No.:
63
25
2
Chemical
ID
No.:
056801
Structures
of
carbaryl
and
major
metabolites
are
shown
below
in
Figure
1.
Figure
1.
Structures
of
Carbaryl
and
Major
Metabolites
Name
Structure
Carbaryl
1
Naphthyl
N
methylcarbamate
5,6
dihydro
5,6
dihydroxy
carbaryl
Figure
1.
Structures
of
Carbaryl
and
Major
Metabolites
Name
Structure
3
From
the
EPA
Technology
Transfer
Network,
Office
of
Air
Quality
Planning
and
Standards,
Air
Toxics
Website
(www.
epa.
gov/
ttn/
atw)
18
OH
5
methoxy
6
hydroxy
carbaryl
1
Naphthol
2.2
Physical
Properties
of
Carbaryl
Physical
state:
white
to
light
tan
solid
Melting
point:
142
0
C
Solubility:
water
(40
ppm
at
25
C),
dimethyl
formamide
(
45
g/
100
mL);
acetone,
cyclohexanone,
and
isophorone
(
25
g/
100
mL);
methylethyl
ketone
(
20
g/
100
mL);
dichloromethane
(
15
g/
100
mL);
ethanol
and
ethyl
acetate
(
10
g/
100
mL);
mixed
aromatic
solvents
and
xylene
(
3
g/
100
mL);
and
kerosene
(
1
g/
100
mL).
Vapor
pressure:
0.000041
mm
Hg
at
26
0
C
3
Specific
gravity:
1.23
at
20
0
C
Octanol/
water
partition
coefficient
(Kow):
217
19
3.0
HAZARD
CHARACTERIZATION
The
hazard
component
of
the
risk
assessment
is
presented
in
this
section.
Section
3.1:
Hazard
Profile
presents
a
discussion
of
the
available
toxicity
data
for
carbaryl.
Section
3.2:
FQPA
Considerations
discusses
the
susceptibility
of
sensitive
populations
such
as
children
and
the
uncertainties
associated
with
that
analysis.
Section
3.3:
Dose
Response
Assessment
describes
which
data
were
selected
for
risk
assessment
purposes.
Section
3.4:
Endocrine
Disruption
describes
issues
related
to
EDSTAC
and
the
screening
process
for
possible
chemicals
of
concern.
3.1
Hazard
Profile
The
updated
Toxicology
Chapter
of
the
RED
was
prepared
by
Dr.
Virginia
Dobozy
(D282980).
The
toxicology
data
base
is
of
good
quality
and
is
essentially
complete.
A
90
day
inhalation
study
with
cholinesterase
measurements
is
required.
The
database
provides
sufficient
information
for
selecting
toxicity
endpoints
for
risk
assessment
and
therefore,
supports
a
reregistration
eligibility
decision
for
the
currently
registered
uses.
Carbaryl
is
a
carbamate
insecticide.
Its
primary
mode
of
toxic
action
is
through
cholinesterase
inhibition
(ChEI)
after
single
or
multiple
exposures.
In
most
of
the
toxicology
studies
in
which
ChEI
was
measured,
it
was
the
endpoint
used
to
set
the
Lowest
Observed
Adverse
Effect
Level
(LOAEL).
The
acute
toxicity
studies
showed
that
carbaryl
was
relatively
toxic
with
acute
oral
dosing
(Tox.
Category
II);
but
the
acute
dermal
and
inhalation
toxicities
were
low
(Tox.
Categories
III
and
IV,
respectively).
Carbaryl
was
not
a
dermal
or
eye
irritant
and
was
not
a
dermal
sensitizer
in
animal
studies
(Table
1).
However,
human
incidents
of
dermal
irritation
and
dermal
manifestations
of
an
allergic
response
have
been
reported
(see
section
7.4
below
for
more
information).
Table
1:
Acute
Toxicity
of
Carbaryl
Guideline
No.
Study
Type
MRIDs
#
Results
Toxicity
Category
81
1
Acute
Oral
rat
(99%
a.
i.)
00148500
LD50
for
males
=
302.6
mg/
kg;
for
females
=
311.5
mg/
kg;
combined
=
307.0
mg/
kg
II
81
2
Acute
Dermal
rabbit
(99%
a.
i.)
00148501
LD50
>
2000
mg/
kg
III
81
3
Acute
Inhalation
rat
(99%
a.
i.)
00148502
LC50
>
3.4
mg/
L
IV
81
4
Primary
Eye
Irritation
rabbit
(99%
a.
i.)
00148503
not
a
primary
eye
irritant
IV
81
5
Primary
Skin
Irritation
rabbit
(99%
a.
i.)
00148504
not
a
primary
skin
irritant
IV
Table
1:
Acute
Toxicity
of
Carbaryl
Guideline
No.
Study
Type
MRIDs
#
Results
Toxicity
Category
20
81
6
Dermal
Sensitization
guinea
pig
(99%
a.
i.)
00148505
negative
NA
81
7
Acute
Delayed
Neurotoxicity
(Hen)
*
negative
at
2000
mg/
kg
(approximate
LD50)
NA
81
8
Acute
Neurotoxicity
rat
43845201
43845204
systemic
LOAEL
=
10
mg/
kg
for
males
and
females
based
on
significant
inhibition
of
RBC,
plasma,
whole
blood
and
brain
cholinesterase;
NOAEL
<
10
mg/
kg
a.
i.
=
active
ingredient
*
Carpenter,
C.
P.,
Weil,
C.
S.,
Palm,
P.
E.,
Woodside,
N.
W.,
Nair,
J.
H.
and
Smyth,
H.
F.
Mammalian
Toxicity
of
1
napthyl
Nmethyl
carbamate
(Sevin
Insecticide).
J.
Agric.
Food
Chem.
9(
1):
30
39,
1961.
The
neurotoxicity
data
showed
that
carbaryl
was
not
a
delayed
neurotoxicant
in
the
hen.
In
the
acute
neurotoxicity
study
in
the
rat
after
a
single
dose
of
10
mg/
kg
carbaryl,
ChEI
was
observed
in
plasma,
whole
blood,
red
blood
cells
(RBC)
and
brain.
At
the
next
higher
dose
(50
mg/
kg),
clinical
signs
typical
of
carbamate
toxicity
were
observed.
In
the
subchronic
neurotoxicity
study
after
90
days
of
administration,
clinical
signs
of
toxicity
were
seen
at
the
same
dose
(10
mg/
kg/
day)
as
plasma,
whole
blood,
RBC
and
brain
ChEI.
There
was
no
evidence
of
structural
neuropathology
in
these
studies.
No
subchronic
studies
in
the
rat
or
dog
are
available,
except
for
the
subchronic
neurotoxicity
study
in
rats
and
4
week
dermal
toxicity
studies
in
rats
(one
with
technical
chemical
and
two
with
formulations).
One
of
the
dermal
toxicity
studies
was
useful
for
risk
assessment.
In
this
study,
the
systemic
NOAEL
was
20
mg/
kg/
day
based
on
decreased
RBC
ChEI
in
males
and
females
and
brain
ChEI
in
males
at
50
mg/
kg/
day.
The
chronic
toxicity
data
showed
that,
in
dogs,
decreases
in
plasma,
RBC
and
brain
ChEI
were
observed
at
10
mg/
kg/
day;
clinical
signs
of
toxicity
were
also
observed
in
both
sexes
at
31
mg/
kg/
day.
Brain
and
plasma
ChEI
were
decreased
in
female
dogs
at
3.1
mg/
kg/
day.
In
the
mouse,
clinical
signs
of
toxicity
were
not
typical
of
ChEI,
but
there
was
ChEI
(plasma,
RBC
and
brain)
at
146
mg/
kg/
day.
In
the
chronic
toxicity
study
in
rats,
carbaryl
at
the
highest
dose
(350
mg/
kg/
day
in
males
and
485
mg/
kg/
day
in
females)
caused
a
variety
of
toxic
effects
in
the
liver,
kidneys
and
urinary
bladder.
It
also
induced
an
increase
in
the
incidence
of
thyroid
follicular
cell
hypertrophy
and
degeneration
of
sciatic
nerves
and
skeletal
muscle.
RBC
ChEI
was
decreased
in
males
at
60
mg/
kg/
day
and
in
females
at
79
mg/
kg/
day.
The
lowest
LOAEL
in
the
chronic
studies
was
in
the
chronic
dog
study,
i.
e.,
3.1
mg/
kg/
day,
which
was
the
lowest
dose
in
females.
In
a
follow
up
5
week
study
in
dogs
to
clarify
the
NOAEL
for
ChEI,
plasma
ChEI
was
decreased
in
males
at
3.83
mg/
kg/
day;
no
effects
were
observed
at
1.43
mg/
kg/
day.
21
In
a
prenatal
developmental
toxicity
study
in
the
rat,
maternal
toxicity
was
observed
at
the
same
dose
(10
mg/
kg/
day)
as
developmental
toxicity;
the
NOAEL
was
4
mg/
kg/
day.
Developmental
effects
included
decreased
fetal
body
weight
and
increased
incomplete
ossification
of
multiple
bones.
In
a
prenatal
developmental
toxicity
study
in
the
rabbit,
the
maternal
and
developmental
LOAELs
were
50
mg/
kg/
day
and
150
mg/
kg/
day,
respectively.
The
respective
NOAELs
were
5
mg/
kg/
day
and
50
mg/
kg/
day.
The
only
evidence
of
developmental
toxicity
was
a
decrease
in
fetal
body
weight.
These
studies
showed
no
evidence
of
a
qualitative
or
quantitative
increased
susceptibility.
In
the
reproduction
study,
there
was
evidence
of
a
quantitative
offspring
susceptibility.
The
LOAEL
for
parental
systemic
toxicity
was
1500
ppm
(92.43
124.33
mg/
kg/
day
for
males
and
110.78
135.54
mg/
kg/
day
for
females)
based
on
decreased
body
weight,
weight
gain,
and
feed
consumption.
The
NOAEL
was
300
ppm
(23.49
31.34
mg/
kg/
day
for
males
and
26.91
36.32
mg/
kg/
day
for
females).
The
LOAEL
for
offspring
toxicity
was
300
ppm
(23.49
31.34
mg/
kg/
day
for
males
and
26.91
36.32
mg/
kg/
day
for
females)
based
on
increased
numbers
of
F2
pups
with
no
milk
in
the
stomach
and
decreased
pup
survival.
The
NOAEL
was
75
ppm
(4.67
5.79
mg/
kg/
day
for
males
and
5.56
6.41
mg/
kg/
day
for
females).
In
the
developmental
neurotoxicity
study,
there
was
evidence
of
qualitative
susceptibility.
Clinical
signs
of
toxicity
and
plasma
and
brain
ChEI
were
seen
in
maternal
animals
at
the
same
dose
(10
mg/
kg/
day)
as
changes
in
brain
morphometric
measurements
(decreases
in
cerebellar
measurements
in
females
on
Day
11
post
partum)
were
observed
in
offspring;
however,
brain
measurements
were
not
conducted
at
the
next
lower
dose.
The
Health
Effects
Division's
(HED)
Cancer
Assessment
Review
Committee
(CARC)(
11/
7/
01)
classified
carbaryl
as
Likely
to
be
carcinogenic
in
humans
based
on
an
increased
incidence
of
hemangiosarcomas
in
male
mice
at
all
doses
tested
(100,
1000
and
8000
ppm).
The
Q1*,
based
on
the
CD
1
mouse
dietary
study
with
¾
Interspecies
Scaling
Factor,
is
8.75
x
10
4
(mg/
kg/
day)
1
in
human
equivalents.
In
addition
to
the
required
carcinogenicity
studies
in
mice
and
rats,
the
registrant
submitted
a
special
study
in
genetically
modified
mice.
Carbaryl
was
administered
to
heterozygous
p53
deficient
(knockout)
male
mice
in
the
diet
at
concentrations
of
up
to
4000
ppm
(716.6
mg/
kg/
day)
for
six
months.
There
was
no
evidence
of
neoplastic
or
preneoplastic
changes
in
the
vascular
tissues
of
any
organ.
A
model
validation
study
demonstrated
that
vascular
tumors
occur
in
heterozygous
p53
deficient
mice
within
six
months
of
administration
of
a
known
genotoxic
carcinogen
(urethane).
A
recent
review
of
the
data
from
the
submitted
studies
and
the
published
literature
show
that
carbaryl
is
clastogenic
in
vitro.
The
wide
variety
of
induced
aberrations
(both
simple
and
complex)
was
consistent
between
the
submitted
micronucleus
study
and
the
open
literature.
However,
there
are
inconsistencies
relative
to
the
requirement
for
S9
activation.
Nevertheless,
the
two
in
vivo
studies
for
micronuclei
induction
or
chromosome
aberrations
were
negative.
Similarly,
the
6
month
p53
knockout
transgenic
mouse
bioassay
was
negative.
Carbaryl
was
also
negative
for
DNA
binding
in
the
livers
of
mice
treated
with
8000
ppm
for
2
weeks.
Metabolism
studies
identified
epoxide
intermediates
of
carbaryl
which
were
found
to
be
conjugated
to
glucuronide,
rapidly
metabolized
and
excreted
as
any
endogenous
epoxide
would
be.
Overall,
these
findings
indicate
that
carbaryl
produces
epoxides
and
its
DNA
reactivity
is
manifested
as
chromosomal
aberrations
in
cultured
mammalian
cells.
Other
in
vitro
22
studies
indicate
carbaryl's
effects
on
karyokinesis
and
cytokinesis,
as
well
as
stress
genes
associated
with
oxidative
damage.
Based
on
these
considerations,
the
CARC
concluded
that
there
is
a
concern
for
mutagenicity,
which
is
somewhat
lessened
because
of
the
lack
of
an
effect
in
in
vivo
mutagenicity
studies.
The
metabolism
data
in
the
rat
indicated
that
radiolabeled
carbaryl
was
readily
absorbed
with
oral
dosing,
distributed
to
various
organs,
metabolized
and
formed
conjugated
metabolites
with
compounds
such
glucuronic
acid.
A
total
of
20
components
was
found,
and
2
major
metabolites
were
identified,
naphthyl
sulfate
and
naphthyl
glucuronide.
Much
of
the
radioactivity
was
eliminated
within
24
hours
after
dosing
(86%
in
urine
and
11%
in
feces).
Seven
days
post
dosing,
negligible
amounts
of
the
administered
dose
were
found
in
tissues.
Several
special
metabolism
studies
were
conducted
to
explore
a
mechanism
for
the
increase
in
tumor
incidence
in
mice.
The
results
appear
to
show
that
high
doses
of
carbaryl
treatment
(1154
mg/
kg)
led
to
a
"phenobarbital"
type
of
induction
of
liver
xenobioticmetabolizing
enzymes
and
interaction
of
carbaryl
with
chromatin
protein
in
mice.
A
dermal
absorption
study
indicated
that
12.7%
of
a
carbaryl
formulation
(43.9%
a.
i.)
was
absorbed.
The
toxicology
profile
for
carbaryl
is
presented
in
Appendix
1.
3.2
FQPA
Considerations
The
HIARC
(February
19,
2002
meeting)
concluded
that
there
is
a
concern
for
pre
and/
or
postnatal
toxicity
resulting
from
exposure
to
carbaryl.
3.2.1
Determination
of
Susceptibility
There
was
no
evidence
of
quantitative
or
qualitative
susceptibility
following
in
utero
exposures
in
developmental
studies
in
the
rat
and
rabbit.
In
the
reproduction
study,
there
was
evidence
of
quantitative
susceptibility
of
offsprings.
The
LOAEL
for
parental
systemic
toxicity
was
based
on
decreased
body
weight,
weight
gain,
and
feed
consumption;
the
NOAEL
was
27
mg/
kg/
day
in
males
and
30
mg/
kg/
day
in
females.
In
the
offspring
the
LOAEL
was
based
on
increased
numbers
of
F2
pups
with
no
milk
in
the
stomach
and
decreased
pup
survival;
the
NOAEL
was
5
mg/
kg/
day
in
males
and
6
mg/
kg/
day
in
females.
No
adverse
effects
were
observed
in
the
reproductive
parameters.
In
the
developmental
neurotoxicity
study,
there
was
evidence
of
qualitative
susceptibility.
For
maternal
toxicity,
the
LOAEL
was
based
on
decreased
body
weight
gain,
alterations
in
Functional
Observational
Battery
measurements
and
inhibition
of
plasma,
whole
blood
and
brain
cholinesterase
activity;
the
NOAEL
was
1
mg/
kg/
day.
For
developmental
neurotoxicity,
the
LOAEL
was
based
on
the
morphometric
changes
seen
in
the
brain
of
the
offsprings;
the
NOAEL
was
1
mg/
kg/
day.
23
3.2.2
Degree
of
Concern
Analysis
and
Residual
Uncertainties
The
HIARC
concluded
that
there
is
no
residual
concern
in
the
two
generation
reproduction
study
because
the
dose
response
effects
in
pups
are
well
characterized
and
the
NOAEL
for
the
offspring
effects
is
above
that
which
was
used
for
establishing
the
chronic
Reference
Dose
(RfD)
for
chronic
dietary
risk
assessment.
The
HIARC
selected
the
LOAEL
of
3.1
mg/
kg/
day
established
in
the
chronic
toxicity
study
in
dogs
for
establishing
the
chronic
RfD.
Since
a
LOAEL
was
used,
an
additional
uncertainty
factor
of
3X
was
applied
(i.
e,
lack
of
a
NOAEL)
to
the
LOAEL.
Although
a
NOAEL
was
not
established
in
this
study,
the
HIARC
determined
that
a
3X
was
adequate
(as
opposed
to
a
higher
value)
because:
1)
cholinesterase
inhibition
in
females
was
not
accompanied
by
clinical
signs;
2)
no
inhibition
was
seen
for
any
cholinesterase
compartment
in
males
at
this
dose;
3)
the
magnitude
of
inhibition
of
plasma
cholinesterase
inhibition
(12
23%
decrease)
was
comparable
to
the
magnitude
of
inhibition
(22%)
seen
in
the
5
week
study
in
dogs
indicating
no
cumulative
effects
following
long
term
exposure;
4)
the
study
was
well
conducted
and
there
are
sufficient
data
from
subchronic
and
chronic
duration
studies
in
the
other
species
which
support
cholinesterase
inhibition
as
the
critical
effect.
In
addition,
based
on
the
cholinesterase
inhibition
data,
the
dog
appears
to
be
more
sensitive
than
the
rat
in
long
term
studies.
Furthermore,
use
of
the
LOAEL
of
3
mg/
kg/
day
from
the
1
year
dog
study
with
an
uncertainty
factor
of
300
results
in
a
NOAEL
of
1
mg/
kg/
day.
This
extrapolated
NOAEL
is
identical
to
that
of
the
offspring
NOAEL
of
1.0
mg/
kg/
day
established
in
the
developmental
neurotoxicity
study.
Thus,
the
NOAEL
of
1
mg/
kg/
day
used
for
establishing
the
chronic
RfD
is
below
the
NOAEL
of
5
mg/
kg/
day
for
offspring
toxicity,
and
the
chronic
RfD
would
be
protective
of
the
effects
of
concern
for
infants
and
children
following
chronic
dietary
exposures.
With
regard
to
the
developmental
neurotoxicity
study,
the
HIARC
concluded
that
there
was
a
low
level
of
concern
based
on
the
following
residual
uncertainties:
°
The
first
uncertainty
was
the
lack
of
a
demonstrated
effect
level
since
morphometric
measurements
of
brains
in
the
offsprings
were
not
performed
at
the
mid
dose
(1
mg/
kg/
day).
However,
this
concern
was
negated
since
even
at
the
high
dose
of
10
mg/
kg/
day,
the
morphometric
changes
were
minimal
and
therefore,
it
is
unlikely
that
adverse
effects
would
be
seen
at
1
mg/
kg/
day,
which
is
10%
of
the
LOAEL.
24
°
The
second
uncertainty
was
the
lack
of
comparative
data
in
adults
and
offspring
for
cholinesterase
inhibition.
This
concern
was
negated
since
no
FOB
alterations
were
seen
in
pups.
Other
studies
in
the
data
base
have
shown
that
when
FOB
alterations
were
seen
in
adult
animals,
they
are
usually
accompanied
with
cholinesterase
inhibition.
Also,
the
results
of
the
National
Institute
for
Environmental
Health
Sciences
study
(discussed
above)
showed
no
difference
in
cholinesterase
inhibition
in
pups
and
adults.
There
was
a
dose
related
decrease
in
cholinesterase
activity
in
the
brain
and
blood
of
dams
at
gestation
day
19
and
fetuses
taken
at
this
time
also
showed
a
very
similar
level
of
fetal
brain
cholinesterase.
The
HIARC
concluded
that
the
NOAEL
of
1
mg/
kg/
day
selected
for
establishing
the
acute
RfD
would
address
the
low
level
of
concern
for
the
residual
concerns
and
would
be
protective
of
the
effects
of
concern
for
infants
and
children
following
a
single
oral
exposure.
3.3
Dose
Response
Assessment
The
HIARC
evaluated
the
toxicology
data
base
of
carbaryl,
reassessed
the
Reference
Dose
(RfD)
established
in
1994
and
selected
the
toxicological
endpoints
for
acute
dietary,
as
well
as
occupational
and
residential
exposure
risk
assessments
at
a
meeting
on
July
7,
1998.
Re
evaluations
of
the
FQPA
Safety
Factor
recommendation
were
done
on
April
28
and
November
15,
1999,
after
the
submission
of
prenatal
developmental
toxicity
studies
in
the
rat
and
rabbit,
respectively.
A
re
evaluation
of
the
endpoints
for
risk
assessment
was
conducted
on
March
1,
2001,
February
19,
2002
and
April
25,
2002.
Table
2
contains
a
summary
of
the
hazard
doses
and
endpoints
selected
for
use
in
the
various
human
health
risk
assessments.
Endpoints
were
selected
for
a
broad
spectrum
of
risk
assessments,
including
acute
and
chronic
dietary,
short,
intermediate
and
long
term
dermal
and
inhalation
exposures
and
short
and
intermediate
term
incidental
exposure.
For
the
chronic
dietary
and
the
long
term
dermal
and
inhalation
exposure
endpoints,
a
LOAEL
was
selected,
which
necessitated
an
additional
3x
uncertainty
factor.
A
common
toxicological
endpoint
exists
for
the
dermal,
inhalation
and
incidental
oral
routes.
Therefore,
the
Margins
of
Exposure
(MOEs)
can
be
combined
for
occupational
and
residential
risk
assessments.
For
acute,
short
,
intermediate
and
long
term
aggregate
risk
assessments,
the
oral,
dermal
and
inhalation
routes
can
be
combined
because
of
the
common
toxicity
endpoint
(ChEI).
Table
2.
Summary
of
Toxicological
Dose
and
Endpoints
for
Carbaryl
for
Use
in
Human
Risk
Assessment
Exposure
Scenario
Dose
(mg/
kg/
day)
&
Total
UF
Hazard
Based
Special
FQPA
Safety
Factor
Endpoint
for
Risk
Assessment
Dietary
&
Nondietary
Ingestion
Risk
Assessments
Acute
Dietary
general
population
including
infants
and
children
NOAEL
=
1
UF
=
100
1
Developmental
Neurotoxicity
rat
LOAEL
=
10
mg/
kg/
day
based
on
an
increased
incidence
of
FOB
changes
on
the
first
day
of
dosing
in
maternal
animals
Acute
RfD
and
aPAD
=
0.01
mg/
kg/
day
Table
2.
Summary
of
Toxicological
Dose
and
Endpoints
for
Carbaryl
for
Use
in
Human
Risk
Assessment
Exposure
Scenario
Dose
(mg/
kg/
day)
&
Total
UF
Hazard
Based
Special
FQPA
Safety
Factor
Endpoint
for
Risk
Assessment
25
Chronic
Dietary
all
populations
LOAEL=
3.1
UF
=
300
1
Chronic
toxicity
dog
LOAEL
=
3.1
mg/
kg/
day
based
on
plasma
and
brain
cholinesterase
inhibition
in
females.
Chronic
RfD
and
cPAD
=
0.01
mg/
kg/
day
[Note:
A
NOAEL
could
not
be
defined
in
this
study.
Therefore,
an
additional
factor
of
3
has
been
applied
to
account
for
the
data
deficiency.]
Short
term
Incidental
Oral
(1
30
Days)
[Residential
Only]
NOAEL=
1
Res.
UF
=
100
1
Developmental
Neurotoxicity
rat
LOAEL
=
10
mg/
kg/
day
based
on
an
increased
incidence
of
FOB
changes
and
decreases
in
RBC,
whole
blood,
plasma
and
brain
cholinesterase
Intermediate
Term
Incidental
Oral
(1
several
months)
[Residential
Only]
NOAEL=
1
Res.
UF
=
100
1
Subchronic
Neurotoxicity
rat
LOAEL
=
10
mg/
kg/
day
based
on
increased
incidence
of
FOB
changes;
decrease
in
RBC,
whole
blood,
plasma
and
brain
cholinesterase.
Non
Dietary
Risk
Assessments
Short
Term
Dermal
(1
30
days)
NOAEL=
20
Res.
UF
=
100
Occ.
UF
=
100
1
4
week
dermal
toxicity
with
technical
rat
systemic
LOAEL
=
50
mg/
kg/
day
based
on
statistically
significant
decreases
in
RBC
cholinesterase
in
males
and
females
and
brain
cholinesterase
in
males.
Intermediate
term
Dermal
(30
days
several
months)
NOAEL=
20
Res.
UF
=
100
Occ.
UF
=
100
1
4
week
dermal
toxicity
with
technical
rat
systemic
LOAEL
=
50
mg/
kg/
day
based
on
statistically
significant
decreases
in
RBC
cholinesterase
in
males
and
females
and
brain
cholinesterase
in
males.
Long
Term
Dermal
(Several
months
to
a
lifetime)
LOAEL=
3.1
Res.
UF
=
300
Occ.
UF
=
300
1
Chronic
toxicity
dog
LOAEL
=
3.1
mg/
kg/
day
based
on
plasma
and
brain
cholinesterase
inhibition
in
females.
[Note:
A
NOAEL
could
not
be
defined
in
this
study.
Therefore,
an
additional
factor
of
3
has
been
applied
to
account
for
the
data
deficiency.
Also,
this
study
is
not
route
specific
as
it
was
conducted
via
oral
administration.
Route
to
route
extrapolation
is
required
using
an
adsorption
factor
of
12.7
percent
which
is
based
on
a
rat
dermal
absorption
study.]
Short
Term
Inhalation
(1
30
days)
NOAEL=
1
Res.
UF
=
100
Occ.
UF
=
100
1
Developmental
Neurotoxicity
rat
LOAEL
=
10
mg/
kg/
day
based
on
an
increased
incidence
of
FOB
changes
and
statistically
significant
decreases
in
RBC,
whole
blood,
plasma
and
brain
cholinesterase
[Note:
This
study
is
not
route
specific
as
it
was
conducted
via
oral
administration.
Route
to
route
extrapolation
is
required
using
an
adsorption
factor
of
100
percent.]
Table
2.
Summary
of
Toxicological
Dose
and
Endpoints
for
Carbaryl
for
Use
in
Human
Risk
Assessment
Exposure
Scenario
Dose
(mg/
kg/
day)
&
Total
UF
Hazard
Based
Special
FQPA
Safety
Factor
Endpoint
for
Risk
Assessment
26
Intermediate
Term
Inhalation
(30
days
several
months)
NOAEL=
1
Res.
UF
=
100
Occ.
UF
=
100
1
Subchronic
Neurotoxicity
rat
LOAEL
=
10
mg/
kg/
day
based
on
increased
incidence
of
FOB
changes;
decrease
in
RBC,
whole
blood,
plasma
and
brain
cholinesterase.
[Note:
This
study
is
not
route
specific
as
it
was
conducted
via
oral
administration.
Route
to
route
extrapolation
is
required
using
an
adsorption
factor
of
100
percent.]
Long
Term
Inhalation
(Several
months
to
a
lifetime)
[Occupational
only]
LOAEL=
3.1
Occ.
UF
=
300
1
Chronic
toxicity
dog
LOAEL
=
3.1
mg/
kg/
day
based
on
plasma
and
brain
cholinesterase
inhibition
in
females.
[Note:
A
NOAEL
could
not
be
defined
in
this
study.
Therefore,
an
additional
factor
of
3
has
been
applied
to
account
for
the
data
deficiency.
Also,
this
study
is
not
route
specific
as
it
was
conducted
via
oral
administration.
Route
to
route
extrapolation
is
required
using
an
adsorption
factor
of
100
percent.]
Cancer
Classification:
C
Q1*
=
8.75
x
10
4
(mg/
kg/
day)
1
3.4
Endocrine
Disruption
EPA
is
required
under
the
Federal
Food
Drug
and
Cosmetic
Act,
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(including
all
pesticide
active
and
other
ingredients)
"may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(EDSTAC),
EPA
determined
that
there
were
scientific
bases
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(EDSP).
When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
carbaryl
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.
27
4.0
NON
OCCUPATIONAL
RISK
ASSESSMENT
AND
CHARACTERIZATION
This
section
of
the
risk
assessment
addresses
exposures
to
individuals
in
the
general
population
that
are
not
exposed
as
part
of
their
employment.
These
exposures
can
occur
through
the
diet
and/
or
they
can
occur
because
people
have
contact
with
carbaryl
residues
while
using
consumer
products
containing
carbaryl
or
by
being
in
areas
that
have
been
previously
treated.
Section
4.1:
Summary
of
Registered
Uses
below
summarizes
available
products
and
also
describes
the
uses
of
those
products.
Products
intended
for
commercial
sales
(e.
g.,
in
agriculture)
and
consumer
products
are
included
as
each
type
of
product
can
contribute
to
non
occupational
exposures
through
the
diet,
via
residential
use,
or
through
commercial
use
in
areas
frequented
by
the
general
population
such
as
golf
courses.
Section
4.2:
Dietary
Risk
Assessment
describes
the
residue
and
consumption
data
used
in
the
dietary
risk
assessment,
the
risks
associated
with
various
populations
of
interest
through
the
diet,
and
characterization
of
those
risks.
Section
4.3:
Water
Risk
Assessment
describes
how
water
concentrations
were
determined,
calculation
of
risks,
and
characterization
of
those
risks.
Section
4.4:
Residential
Risk
Assessment
describes
how
risks
were
calculated
for
people
who
use
consumer
products
containing
carbaryl
and
for
those
who
are
exposed
as
a
result
of
being
in
areas
that
have
been
previously
treated.
4.1
Summary
of
Registered
Uses
All
products
(e.
g.,
manufacturing
and
various
end
use
formulations)
and
the
associated
use
patterns
for
carbaryl
are
described
below.
A
brief
overview
of
the
types
of
equipment
and
application
rates
is
also
provided.
The
information
in
this
section
summarizes
all
use
patterns
of
carbaryl
as
both
commercial
products
and
products
intended
for
sale
to
homeowners
can
both
contribute
to
exposures
in
the
general
population
through
the
diet,
drinking
water,
direct
use
(i.
e.,
for
homeowners
only
in
this
aspect
of
the
risk
assessment)
and
as
a
result
of
people
frequenting
areas
that
have
been
previously
treated
by
either
homeowners
(e.
g.,
lawns
or
gardens)
or
other
public
places
that
could
have
been
commercially
treated
(e.
g.,
golf
courses).
The
need
to
have
a
thorough
understanding
of
the
use
patterns
for
consumer
products
is
self
explanatory.
Understanding
the
use
of
commercial
products
is
key
for
the
development
of
the
dietary
and
drinking
water
assessments.
It
is
also
critical
for
evaluating
some
residential
postapplication
exposures
such
as
for
golfers.
Carbaryl
(1
naphthyl
N
methyl
carbamate)
is
a
broad
spectrum
carbamate
insecticide
marketed
in
a
variety
of
end
use
products
for
both
occupational
and
homeowner
use.
End
use
product
names
include
Adios,
Bugmaster,
Carbamec,
Carbamine,
Crunch,
Denapon,
Dicarbam,
Hexavin,
Karbaspray,
Nac,
Rayvon,
Septene,
Sevin,
Tercyl,
Tornado,
Thinsec,
and
Tricarnam.
Use
sites
include
but
are
not
limited
to
the
following:
fruit
and
nut
trees;
vegetable
crops;
field
and
forage
crops;
grapes;
forestry;
lawns
and
other
turf
such
as
golf
courses;
ornamental
trees,
shrubbery,
annuals,
and
perennials;
wide
area
treatment
targets
such
as
residential
mosquito
adulticide
uses
and
oyster
beds;
poultry
production
facilities;
and
companion
animals
(e.
g.,
dogs
and
cats).
Table
3
summarizes
all
(homeowner
and
occupational
products)
currently
available
technical
and
manufacturing
products
along
with
their
corresponding
EPA
registration
numbers.
28
Table
3:
Technical
and
Manufacturing
Carbaryl
Products
Formulation
EPA
Reg.
No.
(%
active
ingredient)
Technical
34704
707
(99%);
45735
24
(99%);
264
324
(99%),
325
(97.5%);
19713
75
(99%)
Manufacturing
Product
264
328
(80%);
264
325
(97.5%)
769
971
(80%);
5481
190
(46%)
19713
369
(50
%);
432
982
(97.5%);
73049
238
(1%)
Based
on
a
review
(2/
27/
01)
of
the
Office
of
Pesticide
Programs
–
Reference
Files
System
(REFS),
there
are
over
300
active
product
labels
(i.
e.,
includes
both
homeowner
and
occupational
products).
Carbaryl
formulations
include
dusts,
emulsifiable
concentrates,
soluble
concentrates,
water
dispersible
granulars,
flowable
concentrates,
wettable
powders,
granulars,
baits,
pet
dips
and
pet
shampoos,
aerosol
sprays,
ready
to
use
pump
sprayers,
and
pet
collars
(i.
e.,
treated
articles).
Table
4
summarizes
the
approximate
number
of
Section
3
registered
products
in
each
formulation
category
and
the
range
of
percent
active
ingredient.
A
complete
listing
of
all
the
registration
numbers
under
each
category
can
be
found
in
the
Occupational/
Residential
Exposure
Assessment
chapter
(D281418).
This
chapter
also
includes
in
the
Appendices,
the
Qualitative
Usage
Analysis
For
Carbaryl
and
the
RED
Use
Profile
Report
prepared
by
the
Agency's
Biological
and
Economic
Analysis
Division.
Many
of
the
products
described
can
be
used
in
a
variety
of
settings
ranging
from
agriculture
and
commercial
facilities
to
residential
areas.
Table
4:
Carbaryl
End
Use
Product
Formulations
Formulation
Type
Number
of
Products
Range
of
Percent
Active
Ingredient
Emulsifiable
Concentrates
&
Flowable
Concentrates
57
0.3
80
Wettable
Powders
&
Soluble
Granules
36
0.5
95
Dusts
130
0.3
80
Granular
45
1.43
15
Bait
55
1.3
13
Dips,
Shampoos
2
0.
5
60
Pet
collars
(treated
articles)
2
8.
5
16
Ready
to
Use
Pump
Sprayers
&
Aerosol
Cans
6
0.
12
1
29
Equipment
used
to
apply
carbaryl
in
residential
settings
includes
dust
shaker
cans,
garden
hoseend
sprayers,
trigger
sprayers,
low
pressure
handwands,
belly
grinders,
push
type
spreaders,
aerosol
cans,
and
pet
collars.
In
an
occupational
setting,
carbaryl
can
be
applied
by
airblast,
aerial
application,
chemigation,
groundboom,
power
duster,
low
and
high
pressure
handwand,
backpack,
compressed
air
sprayer,
fogger,
hand
held
duster,
hose
end
sprayer,
duster
cans,
and
aerosol
can.
Depending
on
the
crop,
the
maximum
number
of
carbaryl
applications
per
season
can
range
from
1
to
8.
A
variety
of
application
rates
are
available
on
the
carbaryl
labels,
ranging
from
1
lb
ai/
acre
for
curcurbits
to
16
lb
ai/
acre
for
a
foliar
treatment
of
citrus
in
California.
Some
products
are
marketed
in
a
single
marketplace
while
others
are
sold
for
use
in
various
settings.
Based
on
sales
information
provided
by
Aventis
CropScience
at
the
SMART
meeting
with
EPA
on
September
24,
1998,
it
appears
that
approximately
34
percent
of
carbaryl
use
is
by
homeowners
in
residential
settings,
59
percent
is
used
in
agriculture,
and
the
remaining
7
percent
is
used
in
the
nursery,
landscape
and
golf
course
industries.
The
application
parameters
for
major
crop
groups
or
application
targets
were
defined
by
the
physical
nature
of
the
use
site,
the
physical
nature
of
the
formulation,
the
equipment
needed
for
application
and
the
application
rate.
Selected
crop
groupings
and
application
targets
along
with
corresponding
typical
(if
available)
and
maximum
application
rates
that
are
used
in
the
risk
assessment
are
presented
in
Table
5
below.
Table5:
Application
Rates
Considered
in
Risk
Assessment
Crop
or
Target
Occupational
Products
Residential
Products
lb
ai/
1000
ft
2
(units
may
vary)
lb
ai/
A/
acre
(units
may
vary)
max.
apps/
season
lb
ai/
season
Average
Rates
Alfalfa,
clover,
trefoil
1.
5
1/
cutting
1.
5/
cutting
1.
1
Asparagus
2
4
postharvest
3
broadcast
2
postharvest
6
broadcast
10
postharvest
0.9
0.
023
0.
094
Beans
(fresh
&
dried),
cowpeas,
peas
1.5
4
6
0.
9
0.012
0.047
Beets,
carrot,
horseradish,
radish,
parsnip
2
foliar
2.2
soil
broadcast
6
foliar
4
soil
6
0.
8
0.012
0.047
Blueberries
2
foliar
0.5
lb/
1000
ft
2
soil
5
10
1.
7
0.012
0.047
Cole
Crops
(broccoli,
brussel
sprouts,
cabbage,
cauliflower,
chinese
cabbage,
collards,
kale,
kohlrabi,
mustard
greens)
2
foliar
2.2
soil
broadcast
4
6
0.8
0.
012
0.047
Caneberries
2
foliar
2.2
soil
broadcast
5
4
10
Not
specified
1.7
0.
012
0.047
Celery,
Dandelion
2
foliar
2.2
soil
broadcast
4
6
1.0
0.
012
0.047
Citrus
16
(foliar
in
CA
only)
10
(foliar
in
FL
only)
7.5
foliar
1
lb/
100
gal.
1
Not
specified
8
Not
specified
20
Not
specified
20
Not
specified
2.7
to
3.4
(lemons
&
oranges)
0.023
0.176
Corn
(field
and
pop)
2
4
8
1.0
0.
012
0.047
Table5:
Application
Rates
Considered
in
Risk
Assessment
Crop
or
Target
Occupational
Products
Residential
Products
lb
ai/
1000
ft
2
(units
may
vary)
lb
ai/
A/
acre
(units
may
vary)
max.
apps/
season
lb
ai/
season
Average
Rates
30
Corn
(sweet)
2
foliar
2.2
soil
broadcast
8
4
16
Not
specified
1.3
0.
012
0.047
Cranberry
2
5
10
2.0
0.
012
0.047
Cucurbits
(cucumber,
melon,
pumpkin,
squash)
1
6
6
1.1
0.
012
0.047
Fruiting
Vegetable
(tomato,
eggplant,
pepper)
2
7
8
1.0
0.
012
0.047
Grapes
2
5
10
1.4
0.
012
0.047
Grasses
Grown
For
Seed
1.5
2
3
0.
8
(based
on
hay)
Leafy
Vegetable
(head
and
leaf
lettuce,
endive,
mustard
green)
2
foliar
2.2
soil
broadcast
5
4
6
Not
specified
1.1
0.
012
0.047
Nuts
(almond,
chestnut,
pecan,
pistachio,
walnut,
etc.),
foliar
or
dormant/
delayed
5
4
15
2.5
(pecans)
0.047
0.12
Nuts
(almond,
chestnut,
pecan,
walnut),
foliar
in
CA
1
lb
ai/
100
gal
Not
specified
Not
specified
Not
specified
0.047
0.12
Ornamental
2.2
or
2%
solution
1.
5
0.023
Oyster
beds
(SLN
only)
10
Not
specified
Not
specified
Peanut
2
5
8
0.8
0.
012
0.047
Pome
fruit
3
8
15
1.
2
(based
on
apples)
0.012
0.07
Potatoes
&
Tubers
(turnips)
2
6
6
0.8
Rangeland
pastures
1
1
1
0.9
Rice
1.5
2
4
1.
1
Right
of
Way
1.
5
3
0.
4
Sorghum
2
4
6
1.1
Stone
fruit
(apricot,
cherry,
nectarine,
peach,
plum/
prune),
foliar
or
dormant/
delayed
3
4
CA
only
3
foliar
&
1
dormant/
delayed
14
1.1
0.
047
0.12
Stone
fruit
(apricot,
cherry,
nectarine,
peach,
plum/
prune),
foliar
1
lb
ai/
100
gal
Not
specified
Not
specified
Not
specified
0.047
0.12
Strawberries
2
5
10
1.4
0.
012
0.047
Sugar
beets
1.
5
to
2
2
to
4
4
1.3
0.
012
0.047
Sweet
Potatoes
2
foliar
8
lb/
100
gal
drip
8
foliar
Not
specified
8
foliar
1.2
1.6
foliar
Not
specified
0.012
0.047
Sunflower
1.
5
2
3
0.7
0.
012
0.047
Tobacco
2
4
8
1.1
Tree
farm
1
2
0.
7
Turf/
golf
8
liquids
9
granulars
0.
8/
1000sf
2
to
4
0.
047
to
0.25
(lawns)
[maximum
levels
for
different
products]
Wheat,
flax
1.5
2
3
0.
8
Ants
2%
sol
2%
sol
Mosquito
Control
2
Outdoor
Banding
2%
sol
2%
sol
Table5:
Application
Rates
Considered
in
Risk
Assessment
Crop
or
Target
Occupational
Products
Residential
Products
lb
ai/
1000
ft
2
(units
may
vary)
lb
ai/
A/
acre
(units
may
vary)
max.
apps/
season
lb
ai/
season
Average
Rates
4
At
the
present
time,
information
from
the
industry
sponsored
Carbamate
Market
Basket
Survey
has
been
approved
for
use
in
dietary
risk
assessments
with
appropriate
characterization
of
uncertainties
associated
with
the
conduct
of
the
study.
The
primary
concern
was
rubbing
sampled
commodities
during
the
rinsing
process
except
for
broccoli
and
tomato
because
this
created
a
potential
for
residue
loss
from
the
mechanical
action
associated
with
rubbing.
A
separate
assessment
was
also
completed
using
other
sources
of
high
quality
residue
data
(e.
g.,
PDP)
for
comparative
purposes
to
more
completely
inform
the
risk
management
process.
31
Domestic
Animals
(e.
g.,
cats/
dogs)
Dust
0.2
lb
ai/
dog
Sha.
0.01
lb
ai/
dog
Dust
0.2
lb
ai/
dog
Sha.
0.01
lb
ai/
dog
Domestic
Animals
(e.
g.,
cats/
dogs)
1.3
oz/
dog
collar
1.3
oz/
dog
collar
Note:
In
many
cases
an
application
rate
per
area
(e.
g.,
1000
ft
2
)
is
provided
but
a
1
to
2
%
ai
w/
v
solution
can
be
used
to
make
similar
applications
where
volume
outputs
are
difficult
to
regulate
(i.
e.,
handheld
equipment
where
area
treated
is
difficult
to
define).
4.2
Dietary
Risk
Assessment
The
Product
and
Residue
Chemistry
Chapters
(D283328;
May
30,
2002)
and
the
Dietary
Exposure
Analysis
(D281419;
April
28,
2002)
were
prepared
by
Felecia
Fort.
Potential
exposure
to
residues
of
carbaryl
in
the
diet
occurs
through
food
and
water.
Carbaryl
is
used
late
in
the
season
at
maximal
seasonal
rates
of
6
12
lb
ai/
acre.
[Note:
There
is
also
a
section
3
registration
that
allows
use
on
citrus
up
to
16
lb
ai/
acre
only
in
the
state
of
California.]
Post
harvest
intervals
(PHIs)
range
from
1
29
days
but
most
are
one
week
or
less.
The
qualitative
nature
of
carbaryl
residues
in
plants
and
animals
is
adequately
understood.
The
carbaryl
residue
to
be
regulated
in
plants
is
carbaryl
per
se.
The
residues
of
concern
in
meat
and
milk
are
the
free
and
conjugated
forms
of
carbaryl,
5,6
dihydro
5,6
dihydroxy
carbaryl,
and
5
methoxy
6
hydroxy
carbaryl.
Adequate
Pesticide
Data
Program
(PDP)
and
Food
and
Drug
Administration
(FDA)
monitoring
residue
data
are
available
for
the
vast
majority
(>
80%)
of
commodities.
Detectable
residues
were
found
in
31
of
42
crops.
In
field
trials,
residues
were
less
than
the
Limit
of
Quantitation
(LOQ)
in
5
crops
but
were
quantifiable
in
all
other
raw
agricultural
commodities
(RACs).
The
dietary
exposure
assessment
is
a
Tier
3/
4
assessment,
which
is
the
most
highly
refined
assessment
that
can
be
conducted
at
this
time.
HED
has
provided
anticipated
residues
(ARs)
for
carbaryl
based
on
USDA
PDP
and
FDA
monitoring
data,
along
with
field
trial
data,
for
many
commodities.
In
addition,
separate
acute
assessments
were
conducted
incorporating
the
results
of
the
Carbamate
Market
Basket
Survey
(CMBS)
4
.
32
Carbaryl
and
its
degradate
1
naphthol
are
fairly
mobile
but
are
not
likely
to
persist
or
accumulate
in
the
environment.
Available
non
targeted
monitoring
studies
were
of
limited
utility
in
developing
estimated
environmental
concentrations
(EECs)
of
carbaryl
in
water.
Therefore,
screening
models
were
utilized
in
assessing
carbaryl
residues
in
drinking
water
(see
Section
4.3
below
for
more
details).
Section
4.2.1:
Residue
Profile
provides
information
on
the
residue
data
used
to
complete
the
dietary
risk
assessments.
Section
4.2.2:
Acute
Dietary
Risk
Assessment
presents
the
acute
assessment
with
and
without
the
CMBS
data.
Section
4.2.3:
Chronic
Dietary
Risk
Assessment
presents
the
results
for
this
duration
of
exposure.
Section
4.2.4:
Cancer
Dietary
Risk
Assessment
presents
cancer
risks.
Section
4.2.5
Characterization/
Uncertainties
of
the
Risk
Estimates
provides
information
that
should
be
considered
along
with
the
numerical
results
of
this
assessment.
4.2.1
Residue
Profile
Tolerances
for
residues
of
carbaryl
are
currently
expressed
in
terms
of
carbaryl
(1
naphthyl
Nmethylcarbamate
including
its
hydrolysis
product
1
naphthol,
calculated
as
carbaryl,
for
most
raw
crop
commodities
(RACs)
[40
CFR
§180.169(
a)].
The
established
tolerances
for
residues
in/
on
pineapples,
pome
fruits,
avocados,
and
fresh
dill
are
expressed
in
terms
of
carbaryl
per
se
[40
CFR
§180.169(
d)
and
(e)].
Tolerances
for
residues
in
livestock
commodities
are
expressed
as
carbaryl,
including
its
metabolites
1
naphthol
(naphthyl
sulfate),
5,6
dihydrodihydroxy
carbaryl,
and
5,6
dihydrodihydroxy
naphthol,
calculated
as
carbaryl
[40
CFR
§180.169(
b)
and
(c)].
A
tolerance
for
residues
in
pineapple
bran
is
expressed
in
terms
of
carbaryl
per
se
[40
CFR
§186.550].
The
HED
Metabolism
Committee
concluded
that
the
carbaryl
residue
to
be
regulated
in
plants
is
carbaryl
per
se
(DP
Barcode
D221979,
S.
Hummel,
2/
8/
96).
The
Committee
also
concluded
that
carbaryl,
5,6
dihydro
5,6
dihydroxy
carbaryl,
5
methoxy
6
hydroxy
carbaryl
and
all
residues
which
can
be
hydrolyzed
to
carbaryl,
5,6
dihydro
5,6
dihydroxy
carbaryl
and
5
methoxy
6
hydroxy
carbaryl
under
acidic
conditions
should
be
included
in
the
tolerance
expression
and
risk
assessment
for
all
endpoints
of
dietary
concern
for
livestock
commodities
only.
(C.
Olinger,
D255855,
6/
21/
99).
An
interim
tolerance
of
0.5
ppm
has
been
established
for
carbaryl
and
its
1
naphthol
metabolite
in
eggs
[40
CFR
§180.319].
Tolerances
of
2
ppm
and
10
ppm
have
been
established
for
residues
of
carbaryl
in
pineapples
and
bananas,
respectively.
The
registrant
intends
to
support
the
tolerances
for
residues
of
carbaryl
in/
on
these
commodities
as
import
tolerances.
Currently,
the
Codex
MRLs
and
U.
S.
tolerances
are
not
compatible
because
the
U.
S.
tolerance
expression
includes
metabolites.
Once
the
U.
S.
tolerance
definition
is
amended,
it
will
be
compatible
with
the
definition
for
Codex
MRLs.
The
Metabolism
Committee
has
also
recommended
that
the
tolerance
expression
for
livestock
commodities
include
the
free
and
conjugated
forms
of
carbaryl;
5,6
dihydro
5,6
dihydroxy
carbaryl;
and
5
methoxy
6
hydroxy
carbaryl.
The
Codex
MRLs
and
U.
S.
tolerances
cannot
be
made
compatible
for
livestock
commodities
with
respect
to
the
tolerance
definition.
The
reregistration
requirements
for
plant
and
livestock
metabolism
are
fulfilled.
Acceptable
metabolism
studies
depicting
the
qualitative
nature
of
residues
in
lettuce,
radish,
soybeans,
ruminants
and
poultry
have
been
submitted
and
evaluated.
For
the
purpose
of
reregistration,
adequate
magnitude
of
the
residue
data
are
available
on
the
following
crops:
alfalfa,
almond,
asparagus,
beans
(dried
and
succulent),
blueberry,
broccoli,
cabbage,
celery,
cherry,
citrus
fruits,
clover,
corn
(sweet
and
field),
33
cucurbits
(cantaloupes,
cucumbers
and
squash),
cranberry,
flax,
grape,
head
and
leaf
lettuce,
mustard
greens,
okra,
peanut,
peas
(dried
and
succulent),
pecan,
pepper,
pistachio,
pome
fruits,
potato,
prickly
pear
cactus,
raspberry,
rice,
sorghum,
soybean,
spinach,
stone
fruits,
strawberry,
sunflower,
sweet
potato,
tobacco,
tomato,
walnut.
Geographical
representation
is
adequate
and
a
sufficient
number
of
trials
reflecting
representative
formulation
classes
were
conducted.
Carbaryl
residues
were
<LOQ
in/
on
sweet
potato,
sugar
beets,
corn
grain,
flax
seed,
and
peanuts.
Quantifiable
residues
were
detected
in
all
other
RACs.
For
a
given
crop,
residue
levels
were
quite
variable
overall,
probably
owing
to
climactic
variations,
but
were
generally
consistent
within
any
specific
field
trial
location.
There
are
data
gaps
which
are
listed
in
Section
8.0:
Data
Needs/
Label
Requirements.
Adequate
PDP
monitoring
data
were
available
for
the
commodities
potatoes,
carrots,
sweet
potato,
celery,
spinach,
lettuce
(head),
broccoli,
succulent
peas
(processed)
,
succulent
beans,
soybean,
tomatoes,
cantaloupe,
winter
squash,
orange,
orange
juice,
apple,
apple
juice,
pear,
peach,
wheat,
sweet
corn,
banana,
grape,
grape
juice
and
milk.
FDA
monitoring
data
were
used
for
the
commodities,
lettuce
(leaf),
cabbage,
eggplant,
succulent
peas
(fresh),
non
bell
pepper,
bell
pepper,
cucumber,
watermelon,
summer
squash,
cherries,
raspberry,
blueberry,
asparagus,
cranberries,
pineapple,
and
strawberry.
Monitoring
data
were
translated
to
similar
crops
when
possible,
generally
according
to
the
HED
SOP
99.3
"Translation
of
Monitoring
Data".
Monitoring
data
from
the
years
1994
through
1998
(PDP)
and
the
years
1992
through
1998
(FDA)
were
considered.
Field
trial
data
were
used
for
the
commodities,
garden
beets,
turnips,
mustards,
dried
beans,
almonds,
pecans,
walnuts,
field
corn
grain,
rice,
flax
seed,
okra,
olive,
peanuts,
pistachio,
sugar
beets,
dried
peas,
and
sunflower.
HED
conducts
dietary
risk
assessments
using
the
Dietary
Exposure
Evaluation
Model
(DEEM™),
which
incorporates
consumption
data
generated
in
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(CSFII),
1989
1992.
In
this
assessment,
CFSII
data
from
1994
to
1998
were
also
considered
along
with
the
earlier
data
for
comparative
purposes.
Routinely,
the
1989
to
1992
data
are
used
for
risk
assessments;
however,
the
Aventis
Crop
Science
commented
that
the
1994
to
1998
data
should
also
be
considered.
The
Agency
completed
the
analysis
using
both
sets
of
consumption
data
in
response
to
this
comment.
In
these
surveys,
both
3
day
mean
consumption
and
single
day
consumption
information
were
recorded
for
22
demographic
and
socio
economic
subpopulations
including
infants,
children,
and
nursing
women.
For
acute
dietary
risk
assessments,
the
entire
distribution
of
consumption
events
for
individuals
is
multiplied
by
a
randomly
selected
distribution
of
residues
(probabilistic
analysis,
referred
to
as
"Monte
Carlo"
)
to
obtain
a
distribution
of
exposures
in
mg/
kg/
day.
For
chronic
dietary
risk
assessments,
the
3
day
average
for
each
subpopulation
is
combined
with
average
residues
in
commodities
to
determine
average
exposures
(mg/
kg/
day).
Anticipated
residue
estimates
were
prepared
using
USDA
Pesticide
Data
Program
(PDP)
data,
if
available.
Alternatively,
FDA
surveillance
monitoring
data
from
the
years
1992
98
were
used
if
sufficient
samples
were
available.
Data
from
crop
field
trials
were
used
if
there
were
insufficient
PDP
or
FDA
monitoring
data.
In
addition,
separate
acute
assessments
were
conducted
incorporating
the
results
of
the
CMBS
as
described
above
(i.
e.,
rubbing
fruit
may
reduce
residues,
use
of
other
high
quality
data
leads
to
a
more
informed
risk
management
decision).
The
Biological
and
Economic
Analysis
Division
(BEAD)
provided
information
(F.
Hernandez,
34
7/
21/
98)
on
the
percent
crop
treated
(%
CT).
For
the
chronic
analysis,
the
weighted
average
%CT
was
incorporated;
for
the
acute
analysis,
the
estimated
maximum
%CT
was
used
when
appropriate.
In
acute
analyses
(except
blended
commodities)
the
adjustment
for
%CT
is
incorporated
in
the
residue
distribution
files
(RDFs)
via
addition
of
zero
residue
values
corresponding
to
the
%
of
crop
not
treated.
For
blended/
not
furthered
processed
commodities
where
monitoring
data
are
available,
the
entire
distribution
of
monitoring
data
with
no
further
adjustment
for
%CT
were
used.
For
blended/
processed
commodities
where
monitoring
data
are
available
and
for
all
blended
commodities
where
field
trial
data
were
used,
%CT
is
incorporated
into
a
point
estimate.
For
the
chronic
analyses,
the
%CT
is
listed
as
Adjustment
Factor
2
in
the
DEEM
analysis.
One
half
the
weighted
average
of
the
limits
of
detection
was
used
in
the
dietary
assessment
for
all
treated
non
detectable
residues.
Detectable
residues
from
composite
monitoring
data
for
non
blended
food
forms
were
used
to
generate
residue
values
in
single
units
using
the
methods
described
in
the
H.
Allender
paper
dated
5/
26/
99
"Statistical
methods
for
Use
of
Composite
Data
in
Acute
Dietary
Risk
Assessment."
The
"decomposited"
residues
were
then
included
in
residue
distribution
files
(RDF)
for
the
probabilistic
analysis.
BEAD
supplied
percent
crop
treated
data
were
incorporated
into
the
anticipated
residue
or
residue
distribution
file
when
appropriate.
[Note:
Single
serving
peach
PDP
data
were
used
for
non
blended
peach
food
forms
instead
of
data
that
had
been
previously
decomposited
(Allender
method).]
A
separate
dietary
assessment
was
conducted
utilizing
the
CMBS
results.
The
CMBS
Task
Force
conducted
a
year
long,
national
survey
of
carbamate
residues
on
selected
food
commodities
purchased
at
grocery
stores.
Residue
data
from
a
market
basket
survey
are
considered
close
approximations
to
residues
potentially
found
at
most
`dinner
plates'.
These
data
are
generally
considered
the
most
appropriate
survey
type
for
use
in
pesticide
risk
and
exposure
assessment.
The
CMBS
collected
up
to
400
single
serve
samples
of
8
different
crops
(apple,
banana,
broccoli,
grape,
lettuce,
orange,
peach
and
tomato).
These
data
were
used
in
the
acute
dietary
analysis
directly
via
RDFs
incorporating
%CT
for
all
food
forms
which
are
considered
to
be
partially
or
not
blended.
For
blended
commodities,
the
entire
distribution
of
data
with
no
further
adjustment
for
%
CT
was
used.
If
CMBS
data
were
not
available,
then
PDP
or
FDA
monitoring
or
field
trial
data
were
used.
CMBS
data
were
translated
to
similar
commodities
when
feasible;
however,
if
PDP
monitoring
data
were
available
for
the
processed
commodity,
then
CMBS
data
were
not
translated
(i.
e.,
PDP
orange
juice
data
were
used
instead
of
CMBS
data
for
oranges).
The
dietary
risk
assessments
were
completed
with
and
without
the
results
of
the
CMBS
for
comparative
purposes,
again
as
described
above
(i.
e.,
rubbing
fruit
may
reduce
residues,
use
of
other
high
quality
data
leads
to
a
more
informed
risk
management
decision).
Most
of
the
carbaryl
processing
factors
were
obtained
from
processing
studies
submitted
by
the
registrant.
The
rice
processing
factors
were
from
a
review
by
Thurston
Morton
(D216242,
9/
17/
98).
4.2.2
Acute
Dietary
Risk
Assessment
The
following
equations
were
used
to
calculate
dietary
exposure
and
non
cancer
risk
for
carbaryl.
Dietary
exposure
(mg/
kg/
day)
=
consumption
x
residue
35
Dietary
risk
(%
PAD)
=
dietary
exposure
(mg/
kg/
day)
x
100
population
adjusted
dose
(mg/
kg/
day)
The
population
adjusted
dose
(PAD)
is
the
adjusted
RfD
reflecting
the
retention
or
removal
of
the
FQPA
safety
factor.
For
carbaryl,
the
FQPA
safety
factor
has
been
reduced
to
1x.
The
resulting
acute
PAD
(aPAD)
and
chronic
PAD
(cPAD)
are
both
0.01
mg/
kg/
day.
The
doses
and
endpoints
selected
by
the
HIARC
for
these
risk
assessments
are
discussed
in
more
detail
in
Section
3.3:
Dose
Response
Assessment
above.
For
this
Tier
3/
4
Assessment,
estimated
acute
dietary
exposure
at
the
99.9
th
percentile
of
exposure
exceeds
HED's
level
of
concern
without
incorporating
the
CMBS
results
for
all
infants
and
children
(1
6
years)
based
on
1989
to
1992
CFSII
data
(Table
6).
The
highest
exposed
subpopulation
incorporating
all
commodities
using
PDP
and
FDA
monitoring
data
without
CMBS
data
was
all
infants
at
133
percent
of
the
aPAD
while
children
(1
6
years)
were
at
110
percent
of
the
aPAD.
The
same
general
trend
applied
when
the
1994
to
1998
CFSII
data
were
considered
but
risks
were
actually
higher
for
all
subpopulations
(infants
at
134
percent
of
the
aPAD
and
children
(1
to
6
years
old)
at
138
percent
of
the
aPAD).
The
Agency
routinely
uses
the
1989
to
1992
CFSII
data
for
risk
assessments.
However,
Aventis
Crop
Science
commented
that
1994
to
1998
CFSII
data
should
also
be
considered
so
the
Agency
used
both
for
comparative
purposes.
Prior
to
the
calculation
of
these
risk
estimates,
residues
in
poultry
were
the
key
contributors
to
the
risks
for
various
populations.
Since
then,
Aventis
Crop
Science
has
indicated
that
poultry
uses
will
be
deleted
(i.
e.,
poultry
uses
were
not
considered
in
this
assessment).
As
such,
it
appears
that
consumption
of
apples
and
peaches
are
the
critical
contributors
to
acute
dietary
risks.
A
sensitivity
analysis
was
conducted
using
1989
to
1992
CFSII
by
eliminating
these
crops
and
crops
where
no
detectable
residues
were
found
(Table
7).
This
analysis
showed
that
risk
estimates
were
not
significantly
affected
by
assuming
zero
in
place
of
½
LOD
on
samples
reported
as
not
detectable.
Eliminating
apples
reduced
exposures
of
children
(1
6
years)
to
82
percent
of
the
aPAD
but
did
not
significantly
impact
the
risks
for
all
infants
which
were
still
at
118
percent
of
the
aPAD.
Eliminating
peaches
had
the
greatest
impact.
Risks
to
children
(1
6
years)
still
exceeded
100
percent
of
the
aPAD
at
102
percent.
Risks
for
all
infants,
however,
were
reduced
to
72
percent
of
the
aPAD.
Table
6:
Results
of
the
Carbaryl
Acute
Dietary
Analyses
(Market
Survey
Data
Not
Included)
Pop.
Subgroup
99.9
th
Percentile
99
th
Percentile
95
th
Percentile
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
All
Commodities
(1989
92
Consumption
Data)
Gen.
Population
0.
005989
60
0.001381
14
0.000505
5
All
Infants
0.
013251
133
0.003683
37
0.000864
9
Children
1
6
0.
010974
110
0.002552
26
0.001309
13
Children
7
12
0.008721
87
0.001644
16
0.000722
7
Females
13
50
0.004444
44
0.000918
9
0.
000318
3
Males
13
19
yrs
0.
003596
36
0.000899
9
0.
000428
4
Table
6:
Results
of
the
Carbaryl
Acute
Dietary
Analyses
(Market
Survey
Data
Not
Included)
Pop.
Subgroup
99.9
th
Percentile
99
th
Percentile
95
th
Percentile
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
36
Males
20+
yrs
0.
004223
42
0.000929
9
0.
000318
3
Seniors
55+
yrs
0.005789
58
0.001068
11
0.000307
3
All
Commodities
(1994
98
Consumption
Data)
Gen.
Population
0.
006150
62
0.001467
15
0.000508
5
All
Infants
0.
013420
134
0.004027
40
0.000922
9
Children
1
6
0.
013812
138
0.003282
33
0.001460
15
Children
7
12
0.007073
71
0.001473
15
0.000685
7
Females
13
50
0.004794
48
0.000997
10
0.000322
3
Males
13
19
yrs
0.
005181
52
0.000929
9
0.
000420
4
Males
20+
yrs
0.
003940
39
0.000922
9
0.
000336
3
Seniors
55+
yrs
0.005442
54
0.001003
10
0.000313
3
Table
7.
Results
of
the
Carbaryl
Sensitivity
Analyses.
Acute
All
Commodities
at
the
99.9th
percentile
of
exposure
(Market
Basket
Survey
Data
Not
Included)
Pop.
Subgroup
All
commodities
Eliminating
Peaches
Eliminating
Apples
Eliminating
Commodities
with
No
Detectable
Residues
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Gen.
Population
0.
005989
60
0.005451
55
0.004943
49
0.005870
59
All
Infants
0.
013251
133
0.007188
72
0.011784
118
0.012965
130
Children
1
6
0.
010974
110
0.010164
102
0.008201
82
0.0010765
108
Children
7
12
0.008721
87
0.008243
82
0.006867
69
0.008555
86
Females
13
50
0.004444
44
0.004262
43
0.003890
39
0.004434
44
Males
13
19
yrs
0.
003596
36
0.003535
35
0.003014
30
0.003802
38
Males
20+
yrs
0.
004223
42
0.003949
39
0.003575
36
0.004178
42
Seniors
55+
yrs
0.005789
58
0.005456
55
0.005094
51
0.005703
57
When
the
CMBS
data
were
included
in
the
assessment,
the
acute
risk
picture
for
carbaryl
significantly
changed
as
risks
for
all
population
subgroups
considered
were
less
than
100
percent
of
the
aPAD
(Table
8).
If
1989
1992
CFSII
data
are
used,
all
infants
and
children
(1
6
years)
again
had
the
highest
associated
risk
levels
at
73
percent
and
75
percent
of
the
aPAD,
respectively.
For
1994
1998
CFSII
data,
all
infants
and
children
(1
6
years)
also
have
the
highest
risks
at
81
and
93
percent
of
the
37
aPAD,
respectively.
At
the
present
time,
information
from
the
industry
sponsored
Carbamate
Market
Basket
Survey
has
been
approved
for
use
in
dietary
risk
assessments
with
appropriate
characterization
of
uncertainties
associated
with
the
conduct
of
the
study.
Hence,
the
use
of
these
data
in
this
assessment
should
be
considered
with
associated
caveats
(e.
g.,
rubbing
fruit).
Table
8.
Results
of
the
Carbaryl
Acute
Dietary
Analyses
(Market
Basket
Survey
Data
Included)
Pop.
Subgroup
99.9
th
Percentile
99
th
Percentile
95
th
Percentile
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
All
Commodities
(1989
92
Consumption
data)
Gen.
Population
0.
004580
46
0.001251
13
0.000465
5
All
Infants
0.
007272
73
0.002875
29
0.000593
6
Children
1
6
0.
007546
75
0.002283
23
0.001242
12
Children
7
12
0.006126
61
0.001355
14
0.000682
7
Females
13
50
0.003672
37
0.000863
9
0.
000300
3
Males
13
19
yrs
0.
002735
27
0.000818
8
0.
000409
4
Males
20+
yrs
0.
003416
34
0.000842
8
0.
000298
3
Seniors
55+
yrs
0.004601
46
0.000921
9
0.
000277
3
All
Commodities
(1994
98
Consumption
data)
Gen.
Population
0.
004759
48
0.001310
13
0.000468
5
All
Infants
0.
008051
81
0.002624
26
0.000653
7
Children
1
6
0.
009274
93
0.002819
28
0.001352
14
Children
7
12
0.004831
48
0.001226
12
0.000646
6
Females
13
50
0.004194
42
0.000898
9
0.
000301
3
Males
13
19
yrs
0.
004430
44
0.000876
9
0.
000403
4
Males
20+
yrs
0.
003254
33
0.000840
8
0.
000313
3
Seniors
55+
yrs
0.004427
44
0.000836
8
0.
000281
3
4.2.3
Chronic
Dietary
Risk
Assessment
Chronic
dietary
risks
were
calculated
using
the
same
equations
as
described
above
for
the
acute
dietary
risk
estimates
with
different
inputs
appropriate
for
this
exposure
duration.
Chronic
dietary
risks
are
not
of
concern
as
risks
were
<1
percent
of
the
cPAD
for
all
population
subgroups
considered
(Table
9).
The
Carbamate
Market
Basket
Survey
(CMBS)
was
not
used
in
the
calculation
of
chronic
dietary
risks
because
risks
were
low
without
considering
it
and
it
is
not
appropriate
because
it
is
for
single
serving
data.
38
Table
9:
Results
of
the
Carbaryl
Chronic
and
Cancer
Dietary
Analyses.
Chronic
Pop.
Subgroup
1989
92
1994
1998
Exposure
(mg/
kg/
day)
%
cPAD
Exposure
(mg/
kg/
day)
%
cPAD
Gen.
Population
0.
000032
<1
0.000035
<1
All
Infants
0.
000054
<1
0.000059
<1
Children
1
6
years
0.
000057
<1
0.000074
<1
Children
7
12
years
0.
000036
<1
0.000034
<1
Females
13
50
years
0.
000026
<1
0.000028
<1
Males
13
19
years
0.
000022
<1
0.000026
<1
Males
20+
years
0.
000031
<1
0.000032
<1
Seniors
55+
0.000031
<1
0.000030
<1
Cancer
Gen.
Population
0.
000032
2.8
x
10
8
0.000035
3.04
X
10
8
4.2.4
Cancer
Dietary
Risk
Assessment
The
following
equations
were
used
to
calculate
dietary
exposure
and
cancer
risk
using
the
Q1*
approach
for
carbaryl
(i.
e.,
linear,
low
dose
extrapolation).
Cancer
risks
were
only
calculated
for
the
general
population.
Dietary
exposure
(mg/
kg/
day)
=
consumption
x
residue
Dietary
cancer
risk
=
average
food
exposure
(mg/
kg/
day)
x
Q1*
(mg/
kg/
day)
1
Risk
estimates
above
1
x
10
6
are
considered
to
be
of
concern.
Results
indicate
a
maximum
lifetime
risk
of
2.8x10
8
for
the
general
US
population
if
the
1989
to
1992
CFSII
data
were
used.
If
1994
to
1998
CFSII
data
are
considered,
results
are
similar
for
the
general
U.
S.
population
where
cancer
risks
are
3.04x10
8
(Table
9).
The
Carbamate
Market
Basket
Survey
(CMBS)
was
not
used
in
the
calculation
of
chronic
dietary
risks.
4.2.5
Characterization/
Uncertainties
of
the
Dietary
Risk
Estimates
°
No
detectable
residues
were
found
in/
on
several
commodities:
carrots,
chicory,
flax
seed,
horseradish,
parsnip,
salsify,
potato,
celery,
canned
spinach,
head
lettuce,
leaf
lettuce,
rhubarb,
sugarbeets,
Swiss
chard,
brussels
sprouts,
cabbage,
kohlrabi,
soybean,
corn,
banana,
peanuts,
meat,
meat
fat,
and
milk.
Sensitivity
analyses
conducted
by
eliminating
crops
where
no
detectable
residues
were
found
showed
that
risk
estimates
were
not
significantly
affected
by
assuming
zero
in
place
of
½
LOD
on
samples
reported
as
not
detectable.
39
°
The
consumption
database
routinely
used
for
dietary
exposure
analysis,
CSFII
1989
1992,
has
a
limited
number
of
individuals
for
the
age
group
infants
less
than
one
year
old.
The
USDA
has
conducted
the
Supplemental
Children's
Survey
(approximately
5000
children).
For
comparative
purposes,
based
on
comments
from
the
registrant,
the
CSFII
1994
1998
data
have
also
been
used
for
risk
calculations.
The
trends
in
the
results
essentially
did
not
change
significantly
regardless
of
which
data
were
used.
Risks,
in
all
cases,
were
slightly
higher
for
all
subpopulations
using
the
1994
to
1998
data.
°
The
latest
cooking
and
processing
factors
that
were
available
have
been
used
in
the
assessment
(e.
g.,
processing
grapes
to
raisins,
cooking
and
washing
factors
for
peas,
and
oil
production
for
peanuts).
°
The
results
of
the
Critical
Exposure
Contribution
analysis
showed
that
peaches
and
apples
comprised
a
large
percentage
of
the
residues
found
in
the
upper
percentile
tails
of
the
acute
exposure
distribution
for
both
infants
and
children
(i.
e.,
they
were
the
major
risk
contributors
for
children
and
infant
exposure
at
the
upper
percentiles).
°
Detectable
residues
from
composite
monitoring
data
for
non
blended
food
forms
were
used
to
generate
residue
values
in
single
units
using
the
Allender
method.
Though
there
is
a
statistical
basis
for
using
these
data,
some
degree
of
uncertainty
can
be
associated
with
this
method.
[Note:
Peaches
are
a
risk
driver
in
this
assessment
and
this
analysis
is
based
on
single
serving
2000
PDP
data
instead
of
data
that
have
been
decomposited.]
4.3
Estimated
Environmental
Concentrations
In
Water
Dr.
Laurence
Libelo
of
the
Environmental
Fate
and
Effects
Division
(EFED)
provided
an
analysis
of
the
available
monitoring
data
and
a
screening
level
assessment
using
simulation
models
to
estimate
the
potential
Estimated
Environmental
Concentrations
(EECs)
of
carbaryl
in
ground
and
surface
water
(June
28,
2001).
Section
4.3.1:
Environmental
Fate
Characteristics
provides
a
summary
of
the
fate
characteristics
of
carbaryl.
Section
4.3.2:
Monitoring
Data
provides
a
summary
of
the
monitoring
data
that
were
considered
in
this
assessment.
Section
4.3.3:
Modeling
EECs
presents
the
EECs
used
for
comparison
to
the
DWLOCs
(Drinking
Water
Levels
of
Concern)
calculated
for
the
aggregate
risk
assessment
(presented
in
Section
5
below).
4.3.1
Environmental
Fate
Characteristics
Carbaryl
is
considered
to
be
moderately
mobile
and
not
likely
to
persist
or
accumulate
in
the
environment
and
its
degradate,
1
naphthol,
appears
to
be
less
persistent
and
mobile
than
carbaryl
itself.
Under
acidic
conditions
with
limited
microbial
activity
they
may
persist.
Carbaryl
dissipates
in
the
environment
by
abiotic
and
microbially
mediated
degradation.
The
major
degradation
products
are
CO2
and
1
naphthol,
which
is
further
degraded
to
CO2.
Carbaryl
is
stable
to
hydrolysis
in
acidic
conditions
but
hydrolyzes
in
neutral
(t1/
2
=
12
days)
and
alkaline
40
environments
(pH=
9,
t1/
2
=
3.2
days).
Carbaryl
is
degraded
by
photolysis
in
water
(t1/
2
=
21
days).
Under
aerobic
conditions,
the
compound
degrades
rapidly
by
microbial
metabolism,
with
half
lives
of
4
to
5
days
in
soil
and
aquatic
environments.
In
anaerobic
environments
metabolism
is
much
slower
with
½
lives
on
the
order
of
2
to
3
months.
Carbaryl
is
moderately
mobile
in
the
environment
(Kf
=
1.7
to
3.5).
The
major
metabolite
of
carbaryl
degradation
by
abiotic
and
microbially
mediated
processes
is
1
naphthol.
This
degradate
represented
up
to
67
percent
of
the
applied
carbaryl
in
degradation
studies.
It
is
also
formed
in
the
environment
by
degradation
of
napthalene
and
other
polyaromatic
hydrocarbons.
Only
limited
information
is
available
for
the
environmental
transport
and
fate
of
1
naphthol.
While
guideline
studies
were
not
specifically
submitted
for
1
naphthol,
open
literature
data
suggest
it
is
less
persistent
and
less
mobile
than
carbaryl.
4.3.2
Monitoring
Data
Monitoring
data
for
groundwater
and
surface
water
are
limited,
and
targeted
data
are
not
available.
As
reported
in
the
U.
S.
E.
P.
A.
Pesticides
in
Groundwater
Database,
carbaryl
was
detected
in
0.4%
of
wells
sampled.
Carbaryl
was
detected
in
California
(2
out
of
1433
wells),
Missouri
(11
out
of
325
wells),
New
York
(69
out
of
21027
wells)
Rhode
Island
(13
out
of
830
wells)
and
Virginia
(
11
out
of
138
wells)
(Jacoby
et
al.,
1992).
The
maximum
concentration
detected
was
610
µg/
L
in
NY,
though
typically
the
measured
concentrations
were
significantly
lower.
The
EPA
STORET
database
contains
9389
records
indicating
that
analysis
was
done
for
carbaryl.
Of
these,
only
4
were
reported
concentrations
above
the
detection
limits.
These
analyses
were
all
from
one
well
in
Cleveland,
OK
in
1988.
The
4
reported
concentrations
were
between
0.8
and
1
ppb.
Carbaryl
was
detected
at
greater
than
the
detection
limit
(0.003
:
g/
L)
in
1.1%
of
groundwater
samples
in
the
USGS
NAWQA
program.
The
maximum
observed
concentration
was
0.021
:
g/
L.
Detections
were
mainly
from
three
settings:
wheat
(5.8
%
of
well
samples
from
wheat
land
use),
orchards
and
vineyards
(1.7
%
of
well
samples
from
orchard
and
vineyard
land
use),
and
urban
(1.8%
of
urban
groundwater
samples).
A
number
of
field
studies
have
reported
detectable
carbaryl
concentrations
in
surface
waters.
Because
of
limitation
in
the
analytical
methods
used,
there
is
some
question
as
to
the
accuracy
of
carbaryl
analysis.
Poor
analytical
methods
probably
have
resulted
in
lower
detection
rates
and
lower
concentrations
than
actually
present.
Carbaryl
was
detected
in
surface
water
in
46%
of
the
36
NAWQA
study
units
between
1991
and
1998.
Carbaryl
(along
with
carbofuran)
was
one
of
the
two
most
widely
detected
insecticides.
A
significant
portion
of
the
total
carbaryl
applied
was
apparently
transported
to
streams.
Out
of
5220
surface
water
samples
analyzed,
1082
or
about
21
percent
were
reported
as
having
detections
greater
than
the
minimum
detection
limit
(MDL).
The
maximum
reported
concentration
was
5.5
ug/
L.
For
samples
with
positive
detections
the
mean
concentration
was
0.11
:
g/
L
with
a
standard
deviation
of
0.43
:
g/
L.
In
areas
with
high
agricultural
use,
the
load
measured
in
surface
waters
was
relatively
41
consistent
42
across
the
country
at
about
0.1
percent
of
the
amount
used
in
the
basins.
Streams
draining
urban
areas
showed
more
frequent
detections
and
higher
concentrations
than
streams
draining
agricultural
or
mixed
land
use
areas.
Aventis
CropScience
submitted
interim
results
of
an
on
going
surface
water
monitoring
study
of
carbaryl
residues
in
surface
water
in
areas
with
high
agricultural
and
residential
use.
In
this
limited
drinking
water
study,
raw
water
was
collected
at
16
sites
in
agricultural
areas
and
four
in
areas
draining
suburban
areas.
Samples
at
municipal
water
treatment
facilities
were
collected
for
8
12
months.
When
raw
water
showed
positive
detections
for
carbaryl,
finished
water
samples
collected
at
the
same
time
were
analyzed.
In
raw
water
samples
from
suburban
sites,
detectable
residues
in
raw
water
ranged
from
0.002
to
0.023
:
g/
L.
In
samples
from
agricultural
sites,
9
out
of
15
water
sources
had
some
detectable
level
of
carbaryl.
The
detections
were
generally
at
low
levels
with
one
of
about
0.16
:
g/
L
and
one
of
0.031
:
g/
L.
The
rest
were
below
the
level
of
quantitation
(<
0.03
:
g/
L).
Samples
from
finished
water
were
generally
lower
than
raw
water
though
it
appears
that
raw
and
finished
water
sampling
did
not
evaluate
the
same
mass
of
water.
The
data
do
not
give
a
good
indication
of
the
effectiveness
of
treatment
because
samples
exiting
and
entering
the
treatment
plant
were
different.
In
several
cases,
finished
water
had
higher
concentrations
than
raw
water
and
finished
water
had
detectable
carbaryl
when
the
raw
did
not.
The
highest
concentration
measured
was
in
finished
water
(0.16
:
g/
L).
Raw
water
sampled
at
the
same
time
had
a
much
lower
concentration
(0.010
:
g/
L).
This
illustrates
that
carbaryl
contamination
is
transient,
and
that
it
is
unlikely
that
any
sampling
would
catch
the
actual
peak
concentration.
That,
and
the
limited
number
of
sites
sampled,
limit
the
usefulness
of
this
study.
Non
targeted
monitoring,
such
as
the
NAWQA
program
has
shown
that
much
higher
concentrations
occur.
This
study,
while
useful,
does
not
provide
sufficient
information
to
allow
estimation
of
actual
peak
and
mean
concentrations
that
actually
occur
in
all
areas
or
of
the
effect
of
treatment.
4.3.3
Modeling
EECs
Because
of
the
relatively
limited
persistence
of
the
compound
in
the
environment,
it
is
highly
unlikely
that
the
non
targeted
monitoring
studies
which
have
been
completed
detected
the
maximum
concentrations
that
occur.
As
a
result,
the
non
targeted
monitoring
data
have
been
determined
to
be
of
limited
utility
in
developing
estimated
environmental
concentrations
(EECs)
for
ecological
and
human
health
risk
assessment.
Therefore,
computer
modeling
was
used
to
estimate
surface
water
and
groundwater
concentrations
that
could
be
expected
from
normal
agricultural
use
(Table
10).
The
results
of
the
modeling
are
supported
by
the
available
monitoring
data.
These
results
have
been
characterized
as
conservative,
though
not
unreasonable
estimates
of
possible
concentrations
in
drinking
water.
Surface
Water
Modeling:
Computer
modeling
with
the
EPA
PRZM3.12
and
EXAMS
2.97.7
programs
were
used
to
estimate
the
concentration
of
carbaryl
in
surface
water.
Index
reservoir
scenarios
corrected
for
Percent
Cropped
Area
(PCA)
for
representative
crops
were
used.
Three
different
application
rates
were
used
in
modeling:
the
maximum
allowed
on
the
label
for
the
specific
crop,
an
"average"
rate
and
the
maximum
rate
reported
to
actually
be
used.
EECs
varied
greatly
depending
on
the
geographic
location,
crop
and
application
rate.
The
maximum
calculated
acute
and
chronic
EECs
43
(494
ppb
and
28
ppb,
respectively)
resulted
from
use
on
citrus
in
Florida.
Modeling
"average"
and
maximum
resulting
use
rates
gave
EEC
values
generally
40
60%
lower
than
maximum.
The
source
of
drinking
water
in
relation
to
the
EECs
must
be
carefully
considered
when
using
these
data.
In
this
case,
the
results
for
Florida
provided
the
highest
estimates,
however;
in
Florida
the
majority
of
drinking
water
is
derived
from
groundwater
(>
90%)
so
high
surface
water
concentrations
do
not
necessarily
indicate
high
exposure.
As
a
result,
both
Florida
and
the
results
for
Oregon
apples
have
been
considered
in
the
aggregate
assessment
(see
Section
5.0
for
more
information).
The
EECs
for
Oregon
apples
are
the
next
highest
values
for
both
the
acute
and
chronic
estimates.
Ground
Water
Modeling:
SCI
GROW
was
used
to
calculate
a
groundwater
screening
exposure
value
to
be
used
in
determining
the
potential
risk
to
human
health.
Carbaryl
chemical
properties
are
outside
the
range
of
values
for
which
SCI
GROW
was
developed
(i.
e.,
aerobic
metabolism
is
faster
and
its
partition
coefficient
is
larger
which
equates
to
less
leaching
than
the
reference
compounds
both
factors
indicate
carbaryl
degrades
faster).
SCI
GROW
estimates
for
groundwater
EECs
may
not
predict
with
complete
accuracy,
maximum
levels
because
the
concentrations
calculated
are
90
day
averages.
It
is
possible;
therefore,
that
groundwater
concentration
peaks
could
not
be
identified.
Groundwater
levels
are
anticipated,
however,
to
be
more
stable
over
time
than
surface
water
concentrations.
Table
10:
Carbaryl
Drinking
Water
Estimated
Environmental
Concentrations
(EECs)
Crop
Application
Rate
Descriptor
Number
of
Applications
per
Year
Pounds
A.
I.
per
application
Water
Acute
(ppb)
(1
in
10
year
peak
single
day
concentration)
Water
Chronic
(ppb)
(1
in
10
year
annual
average
concentration)
Source:
Surface
Water
(PRZM/
EXAMs)
Sweet
Corn
(OH)
(PCA
=
0.46)
Maximum
1
8
2
37
3.2
Average
2
2
3.
4
45
2.2
Maximum
3
Reported
3
1
15
0.9
Source:
Surface
Water
(PRZM/
EXAMs)
Field
Corn
(OH)
(PCA
=
0.46)
Maximum
1
4
2
30
2.1
Average
2
2
1
13
0.6
Maximum
3
Reported
2
1.
520
1
Source:
Surface
Water
(PRZM/
EXAMs)
Apples
(OR)
(PCA
=
0.87)
Maximum
1
5
2
144
9
Average
2
2
1.
2
12
0.7
Maximum
3
Reported
2
1.
625
1
Source:
Surface
Water
(PRZM/
EXAMs)
Sugar
Beats
(MN)
(PCA
=
0.87)
Maximum
1
2
1.
519
2
Average
2
1
1.
5
12
1.1
Maximum
3
Reported
1
1.
2
9
0.
9
Source:
Surface
Water
(PRZM/
EXAMs)
Citrus
(FL)
(PCA
=
0.87)
Maximum
1
4
5
494
28
Average
2
2
3.
4
246
11
Table
10:
Carbaryl
Drinking
Water
Estimated
Environmental
Concentrations
(EECs)
Crop
Application
Rate
Descriptor
Number
of
Applications
per
Year
Pounds
A.
I.
per
application
Water
Acute
(ppb)
(1
in
10
year
peak
single
day
concentration)
Water
Chronic
(ppb)
(1
in
10
year
annual
average
concentration)
44
Maximum
3
Reported
3
4.
26
411
16
Source:
Surface
Water
Monitoring
5.5
(Maximum
Observed
Concentration)
Source:
Groundwater
(SCI
GROW)
Maximum
1
5
40.
8
0.
8
Source:
Groundwater
(NAWQA
Monitoring
Data)
0.02
0.02
1
Maximum
application
rate
on
label
2
Average
application
rate
from
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD
3
Maximum
rate
of
application
reported
in
DOANES
survey
data
4.4
Residential
Risk
Assessment
The
residential
risk
assessment
addresses
exposures
that
individuals
receive
through
their
use
of
consumer
products
that
contain
carbaryl
and
those
exposures
one
could
receive
from
frequenting
areas
that
have
been
previously
treated
with
carbaryl
such
as
a
home
lawn,
a
garden,
or
a
golf
course.
Carbaryl
can
also
be
applied
in
wide
area
treatments
such
as
on
oyster
beds
or
as
a
mosquito
adulticide.
These
exposures
have
also
been
addressed
in
this
assessment.
The
Occupational
and
Residential
Exposure
Assessment
(D281418)
was
prepared
by
Jeff
Dawson
with
the
exception
of
the
tobacco
assessment
completed
by
Dr.
Virginia
Dobozy.
The
document
D281418
contains
detailed
descriptions
of
the
data
used,
methods,
and
risks
calculated
for
each
scenario.
Please
refer
to
that
document
for
more
specific
information.
Section
4.4.1:
Home
Uses
provides
more
specific
information
pertaining
to
how
carbaryl
consumer
products
are
used
in
addition
to
the
information
presented
above
in
Section
4.1:
Summary
of
Registered
Uses
as
it
applied
more
directly
to
the
residential
risk
assessment.
Section
4.4.2:
Residential
Handler
Risk
Assessment
describes
the
data,
methods,
and
risk
results
(both
cancer
and
noncancer)
associated
with
the
use
of
consumer
products
which
contain
carbaryl.
Section
4.4.3:
Residential
Postapplication
Risk
Assessment
describes
the
data,
methods,
and
risk
results
associated
with
exposures
to
the
general
population
including
adults,
infants,
and
youth
aged
children
that
occur
from
frequenting
treated
areas.
Section
4.4.4:
Residential
Risk
Characterization
provides
information
pertaining
to
the
quality
of
the
assessment
including
data
used,
uncertainties
with
the
methods,
and
any
other
information
45
that
might
be
used
to
describe
the
quality
of
the
results.
Section
4.4.5:
Risks
Associated
With
Use
In
Tobacco
describes
how
risks
were
calculated
for
smokers
who
may
consume
carbaryl
treated
tobacco
in
their
cigarettes.
Section
4.4.6:
Other
Residential
Uses
characterizes
other
potential
sources
of
exposure
outside
of
those
quantitatively
described
in
this
assessment.
4.4.1
Home
Uses
Carbaryl
is
a
widely
used
consumer
product.
Available
products
include
liquids,
wettable
powders,
and
dusts
for
insect
control
on
fruits,
vegetables,
ornamentals,
and
lawns.
Products
for
flea
control
on
pets
are
also
available.
Some
of
the
equipment
used
in
application
includes
dust
shaker
cans,
garden
hose
end
sprayers,
trigger
sprayers,
low
pressure
handwands,
belly
grinders,
push
type
spreaders,
aerosol
cans,
and
pet
collars.
In
addition
to
the
information
presented
in
Section
4.1:
Summary
Of
Registered
Uses,
Aventis
Crop
Science
at
the
time
of
the
September
24,
1998
SMART
Meeting
also
presented
the
following
information
that
is
key
to
interpreting
the
residential
risk
assessment.
Carbaryl
accounted
for
approximately
9
percent
of
the
total
residential
insecticide
market
and
was
ranked
fourth
on
the
list
behind
the
pyrethroids,
chlorpyrifos,
and
diazinon.
In
addition,
the
registrant
also
presented
the
following:
°
According
to
the
registrant,
insect
control
on
vegetables
(~
58%
of
users),
annuals
(~
50%
of
users),
lawns
(~
35%
of
users),
trees/
shrubs
(~
34%
of
users)
account
for
the
majority
of
homeowner
uses
for
carbaryl.
Pet
uses
also
accounted
for
~13
percent
of
users.
°
The
annual
frequency
of
use,
for
all
crops/
targets,
was
reported
to
be
at
the
60
th
percentile
for
1
to
2
times
per
year
and
at
the
84
th
percentile
for
5
times
per
year.
°
Aphids,
ants,
fire
ants,
fleas,
and
slugs/
snails
are
predominant
pests
controlled
by
residential
carbaryl
users
(~
30
down
to
15%
of
users,
respectively).
°
Most
(75%)
of
vegetable
gardens
treated
with
carbaryl
are
<800
ft
2
but
~8
percent
are
between
800
and
1500
ft
2
,
~9
percent
are
between
1500
and
5000
ft
2
,
and
~6
percent
are
greater
than
5000
ft
2
.
Tomatoes,
peppers,
cucumbers,
beans,
and
fruit
trees
represent
the
most
treated
garden
plants.
°
Most
(82%)
of
flower
gardens
treated
with
carbaryl
are
<500
ft
2
but
~10
percent
are
between
500
and
1200
ft
2
,
and
~8
percent
are
greater
than
1200
ft
2
.
Roses,
shrubs,
and
certain
annuals
represent
the
most
treated
flowering/
ornamental
plants.
°
Dusts
(65%)
and
liquid
concentrates
(25%)
account
for
most
carbaryl
sales
in
the
residential
annual
market
of
2
million
pounds
per
year.
4.4.2
Residential
Handler
Risk
Assessment
The
anticipated
use
patterns
and
current
labeling
indicate
17
major
residential
exposure
scenarios,
based
on
the
types
of
equipment
and
techniques,
in
which
homeowners
can
be
exposed
to
5
PHED
is
a
generic
database,
which
includes
the
results
of
over
100
exposure
studies,
developed
by
US
EPA,
Pest
Management
Regulatory
Agency/
Health
Canada
and
the
California
Department
of
Pesticide
Regulation,
in
cooperation
with
the
pesticide
industry.
46
carbaryl
during
the
application
process.
The
quantitative
exposure/
risk
assessment
developed
for
residential
handlers
is
based
on
these
scenarios.
For
most
scenarios,
multiple
uses
and
application
rates
were
considered
for
a
total
of
54
distinct
combinations.
The
17
major
scenarios
include:
(1)
Garden
Uses:
Ready
to
use
Trigger
Sprayer;
(2)
Garden
Uses:
Ornamental
Duster;
(3)
Garden
Uses:
Hose
end
Sprayer;
(4)
Garden
Uses:
Low
Pressure
Handwand;
(5)
Tree/
ornamental
Uses:
Low
Pressure
Handwand;
(6)
Tree/
ornamental
Uses:
Hose
end
Sprayer;
(7)
Garden
Uses:
Backpack
Sprayer;
(8)
Lawncare
Liquid
Uses:
Hose
end
Sprayer;
(9)
Pet
(Dog
and
Cat)
Uses:
Dusting;
(10)
Pet
(Dog
and
Cat)
Uses:
Liquid
Application;
(11)
Lawncare
Granular
and
Bait
Uses:
Belly
Grinder;
(12)
Lawncare
Granular
and
Bait
Uses:
Push
type
Spreader;
(13)
Ornamental
and
Garden
Uses:
Granulars
and
Baits
By
Hand;
(14)
Various
Pest
Uses:
Aerosol
Cans;
(15)
Pet
(Dog
and
Cat)
Uses:
Collars;
(16)
Garden
and
Ornamental
Uses:
Sprinkler
Can;
and
(17)
Garden
and
Ornamental
Uses:
Paint
on.
Data
and
Assumptions
A
series
of
assumptions
and
exposure
factors
served
as
the
basis
for
completing
the
residential
handler
risk
assessments,
as
described
below.
°
The
unit
exposure
values
used
in
this
assessment
were
based
on
three
carbaryl
specific
residential
handler
studies
which
quantified
exposures
during
pet
treatments
with
a
dust;
applications
to
gardens
using
a
ready
to
use
trigger
sprayer,
a
dust,
a
hose
end
sprayer,
and
a
low
pressure
handwand;
and
during
applications
to
trees
using
a
low
pressure
handwand
and
a
hose
end
sprayer.
Two
other
studies
completed
by
the
Outdoor
Residential
Exposure
Task
Force
(ORETF)
and
the
Pesticide
Handlers
Exposure
Database
(Version
1.1
August
1998)
(PHED)
5
were
also
used
as
sources
of
surrogate
information.
[Note
to
Risk
Managers:
There
is
no
data
compensation
issue
associated
with
the
use
of
the
ORETF
data
in
the
carbaryl
risk
assessment
because
Aventis
CropScience,
the
registrant
for
carbaryl,
is
a
member
of
the
ORETF].
Summaries
of
the
five
studies
are
included
in
the
Occupational
and
Residential
Risk
Assessment
(D281418).
These
studies
are
all
considered
to
be
of
high
quality.
The
quality
of
the
data
in
PHED
varies
from
scenarios
that
meet
study
guideline
requirements
to
others
where
a
limited
number
of
poor
quality
data
points
are
available.
However,
in
all
cases,
the
data
used
represent
the
best
available
for
the
scenario.
The
PHED
unit
exposure
values
range
between
geometric
mean
and
median
of
available
exposure
data.
When
data
from
other
studies
were
used,
the
47
appropriate
statistical
measure
of
central
tendency
was
used.
Central
tendency
values,
coupled
with
other
inputs
used
by
HED,
are
thought
to
result
in
conservative,
deterministic
estimates
of
risk.
For
pet
collars
only,
a
scenario
from
the
SOPs
For
Residential
Exposure
Assessment
not
based
on
monitoring
data
was
used
to
calculate
exposures.
The
factors
derived
from
the
SOPs
are
generally
thought
to
be
conservative.
°
Average
body
weight
of
adult
handlers
is
assumed
to
be
70
kg
because
the
toxicology
endpoint
values
used
for
the
risk
assessments
are
appropriate
for
average
adult
body
weight
representing
the
general
population.
No
specific
effects
were
observed
consistently
in
the
toxicology
studies
to
indicate
an
increased
sensitivity
of
one
gender
over
another.
°
Homeowner
handler
assessments
were
completed
based
on
individuals
wearing
shorts
and
shortsleeved
shirts.
°
Homeowner
handlers
are
expected
to
complete
all
tasks
associated
with
the
use
of
a
pesticide
product
including
mixing/
loading,
if
needed,
as
well
as
the
application;
°
Label
maximum
use
rates
and
use
information
specific
to
residential
products
served
as
the
basis
for
the
risk
calculations.
If
additional
information,
such
as
average
or
typical
rates,
were
available,
these
values
were
used
as
well
in
order
to
allow
risk
managers
to
make
a
more
informed
risk
management
decision.
Average
application
rates
were
available
from
the
SMART
meeting
and
BEAD's
Quantitative
Usage
Analysis
(QUA).
These
data
indicate
that
in
most
cases,
average
application
rates
differ
from
maximum
application
rates
by
a
factor
of
approximately
two.
The
average
application
rates
identified
from
the
studies
conducted
by
Aventis
CropScience
were
also
considered.
°
The
exposure
duration
(i.
e.,
years
per
lifetime)
values
in
the
cancer
risk
assessment
are
consistent
with
those
used
for
other
chemicals
(i.
e.,
50
years
with
home
use
chemicals
and
70
year
lifetime).
Cancer
risks
were
calculated
assuming
one
exposure
per
year.
In
addition
the
number
of
days
of
exposure
per
year
which
could
occur
under
the
ceiling
established
by
an
acceptable
risk
level
of
1x10
6
were
also
calculated.
These
estimates
can
then
be
compared
to
the
annual
use
frequency
of
1
2x
(60
th
percentile)
and
5x
(84
th
percentile)
presented
at
the
SMART
meeting.
[Note:
It
is
the
understanding
of
the
Agency
that
Aventis
Crop
Science
is
also
submitting
a
use
analysis
based
on
the
Residential
Exposure
Joint
Venture
(REJV)
survey
which
could
possibly
refine
these
estimates.
The
Agency
will
consider
these
data
as
appropriate.]
48
°
Calculations
were
based
on
scenarios
in
the
home
that
would
reasonably
be
treated
in
a
day
(but
would
not
necessarily
take
more
than
an
hour
or
two)
such
as
the
size
of
a
lawn,
the
size
of
a
garden,
the
amount
that
can
be
applied
with
a
piece
of
equipment,
or
the
number
of
pets
an
individual
might
keep.
Based
on
Agency
Exposure
SAC
Policy
12:
Recommended
Revisions
To
The
Standard
Operating
Procedures
For
Residential
Exposure
Assessment,
the
daily
volumes
handled
and
area
treated,
excerpted
from
the
policy,
used
in
each
residential
scenario
include
(along
with
corresponding
inputs
defined
from
carbaryl
studies
and
the
SMART
meeting
for
a
comparative
analysis
to
allow
for
a
more
informed
risk
management
decision):
°
1
container
of
each
ready
to
use
non
pet
product
including
garden
dusts,
trigger
sprayers
and
aerosol
cans
(scenarios
for
25%
and
50%
used
of
the
total
product
volume
were
also
presented
for
the
trigger
sprayer
and
garden
dust
scenarios
to
allow
for
a
more
informed
risk
management
decision);
°
½
container
of
each
ready
to
use
pet
product,
including
dusts
and
liquid
shampoos;
°
1
pet
collar;
°
100
gallons
of
finished
spray
output
for
hose
end
sprayers;
°
5
gallons
when
mixing/
loading/
applying
liquids
with
a
backpack
sprayer
or
a
low
pressure
handwand
sprayer;
value
was
also
used
for
sprinkler
can
applications;
°
1
gallon
of
paint
on
solution
for
ornamental/
garden
uses;
°
20,000
square
feet
to
represent
the
surface
area
treated
for
broadcast
applications
to
lawns;
°
1000
square
feet
as
the
treatment
area
for
many
spot
applications
in
lawns,
gardens,
and
ornamentals
(this
value
used
as
appropriate
when
application
rates
were
based
on
a
square
foot
basis
for
spot
type
treatments);
and
°
5
mounds
per
day
treated
for
fire
ant
applications.
°
For
direct
pet
treatments,
the
Residential
SOPs
were
used
to
define
the
amount
of
chemical
that
can
be
used
to
treat
single
animals,
which
was
then
used
to
calculate
total
human
dose
levels.
The
actual
per
animal
application
rates
used
were
½
of
6
oz.
bottle
for
liquid
shampoo
(0.5%)
and
½
of
4
lb.
container
for
powders
(10%).
4.4.2.1
Residential
Handler
Noncancer
Risks
Noncancer
risks
were
calculated
using
the
Margin
of
Exposure
(MOE)
approach,
which
is
a
ratio
of
the
body
burden
(exposure)
to
the
toxicological
endpoint
of
concern.
Short
term
dermal
MOEs
were
calculated
using
a
NOAEL
of
20.0
mg/
kg/
day
from
the
21
day
dermal
toxicity
study
in
rats
with
technical
material
and
short
term
inhalation
MOEs
were
calculated
using
a
NOAEL
of
1
mg/
kg/
day
from
the
oral
developmental
neurotoxicity
study
in
rats.
Body
burden
values
were
determined
by
first
calculating
daily
exposures
using
application
parameters
(i.
e.,
rate
and
area
treated)
along
with
unit
exposure
levels.
Exposures
were
then
normalized
by
body
weight
and
adjusted
for
absorption
factors
(100
percent
for
both
dermal
and
inhalation)
as
appropriate
to
calculate
average
daily
dose
levels
(i.
e.,
body
burdens)
as
illustrated
in
equation
below.
49
Daily
Exposure
(mg
ai/
day)
=
Unit
Exposure
(mg
ai/
lb
ai)
x
Application
Rate
(lb
ai/
A)
x
Daily
Acres
Treated
(A/
day)
Where:
Daily
Exposure
=
Amount
deposited
on
the
surface
of
the
skin
that
is
available
for
dermal
absorption
or
amount
that
is
inhaled,
also
referred
to
as
potential
dose
(mg
ai/
day);
Unit
Exposure
=
Normalized
exposure
value
derived
from
August
1998
PHED
Surrogate
Exposure
Table
and
various
referenced
exposure
studies
noted
above
(mg
ai/
lb
ai);
Application
Rate
=
Normalized
application
rate
based
on
a
logical
unit
treatment
such
as
acres
or
gallons,
maximum
and
typical
values
are
generally
used
(lb
ai/
A);
and
Daily
Acres
Treated
=
Normalized
application
area
based
on
a
logical
unit
treatment
such
as
acres
(A/
day)
or
gallons
per
day
can
be
substituted
(gal/
day).
The
dermal
absorption
factor
of
100
percent
based
on
an
absorption
study
in
rats
was
used
for
all
dermal
calculations
since
no
route
to
route
conversion
was
required.
No
specific
inhalation
absorption
factor
is
available
for
carbaryl.
Therefore,
a
factor
of
100
percent
was
used
for
route
to
route
calculations
as
is
done
with
all
pesticides.
MOEs
were
calculated
using
the
following
formula.
MOE
=
NOAEL
(mg
ai/
kg/
day)
Average
Daily
Dose
(mg
ai/
kg/
day)
Where:
MOE
=
Margin
of
exposure,
value
used
to
represent
risk
or
how
close
a
chemical
exposure
is
to
being
a
concern
(unitless);
Average
Daily
Dose
=
The
amount
as
absorbed
dose
received
from
exposure
to
a
pesticide
in
a
given
scenario
(mg
pesticide
active
ingredient/
kg
body
weight/
day);
and
NOAEL
=
No
observed
adverse
effect
level
or
dose
level
in
a
toxicity
study
where
no
observed
adverse
effects
occurred
in
the
study
(mg
pesticide
active
ingredient/
kg
body
weight/
day).
A
combined
(dermal
and
inhalation)
MOE
was
determined
because
common
toxicity
(cholinesterase
inhibition)
endpoints
were
used
to
calculate
dermal
and
inhalation
risks
for
each
exposure
duration.
The
following
formula
was
used
to
calculate
total
MOE
values
by
combining
the
route
specific
MOEs:
MOE
total
=
1/((
1/
MOE
a)
+
(1/
MOE
b)
+....
(1/
MOE
n))
Where:
MOE
a,
MOE
b,
and
MOE
n
represent
MOEs
for
each
exposure
route
of
concern
Short
term
risks
for
residential
handlers
(intermediate
term
scenarios
are
not
thought
to
exist
because
of
the
sporadic
nature
of
applications
by
homeowners)
are
presented
in
Table
11.
For
most
scenarios
(40
out
of
52),
risks
are
not
of
concern
because
MOEs
exceed
the
required
uncertainty
factor
of
100.
As
expected,
the
scenarios
for
which
MOEs
do
not
meet
or
exceed
100
have
a
relatively
high
unit
exposure
associated
with
them
or
the
amount
of
chemical
used
over
a
day
is
relatively
high
(based
on
high
application
rates
and/
or
high
amounts
of
area
treated).
The
use
of
dusts
in
gardens
and
for
pet
50
grooming
along
with
some
liquid
sprays
on
ornamentals
appear
to
be
the
most
problematic
scenarios.
Unlike
the
occupational
handler
scenarios,
the
use
of
different
levels
of
personal
protective
clothing
and
equipment
is
not
considered
for
residential
handlers
because
of
a
lack
of
availability,
training,
and
maintenance.
[Note:
Scenarios
where
MOEs
are
of
concern
(i.
e.,
<100)
for
are
highlighted
in
the
table.]
TABLE
11
CARBARYL
NONCANCER
MOEs
ATTRIBUTABLE
TO
COMBINED
SHORT
TERM
HOMEOWNER
HANDLER
DERMAL
AND
INHALATION
EXPOSURES
SCEN.
SCEN.
DESCRIPTOR
CROP
TYPE
OR
TARGET
EXPOSURE
FACTORS
DERMAL
MOEs
INHALATION
MOEs
COMBINED
MOEs
APPL.
RATE
(lb
ai/
unit)
BASIS
FOR
RATE
(defines
unit
treated)
TREATED
UNITS
ACTIVE
USED
(lb
ai/
event)
1
Garden:
Ready
to
Use
Trigger
Sprayer
(MRID
444598
01)
Vegetables/
Ornamentals
0.003
32
oz
bottle
0.126
%
(769
977)
0.25
0.00075
34567.9
1393034.8
33730.9
Vegetables/
Ornamentals
0.003
32
oz
bottle
0.126
%
(769
977)
0.5
0.0015
17284.0
696517.4
16865.4
Vegetables/
Ornamentals
0.003
32
oz
bottle
0.126
%
(769
977)
1
0.003
8642.0
348258.7
8432.7
Average
Study
Use
Rate
0.012
(lb
ai/
1000
ft2)
1
0.012
2160.5
87064.7
2108.2
2
Garden/
Ornamental
Dust
(MRID
444598
01)
Vegetables/
Ornamentals
0.4
4
lb
bottle
10%
(239
1513)
0.25
0.1
94.6
804.6
84.6
Vegetables/
Ornamentals
0.4
4
lb
bottle
10%
(239
1513)
0.5
0.2
47.3
402.3
42.3
Vegetables/
Ornamentals
0.4
4
lb
bottle
10%
(239
1513)
1
0.4
23.6
201.1
21.2
Average
Study
Use
Rate
0.079
(lb
ai/
1000
ft2)
1
0.079
119.7
1018.5
107.1
3
Garden:
Hose
End
(MRID
444598
01)
General
Use
(2%
soln)
0.02
(lb
ai/
gal
spray
applied)
100
2
20.6
17500.0
20.6
Perimeter
Nuisance
Pest
0.19
(lb
ai/
1000
ft2)
1
0.19
216.7
184210.5
216.5
Vegetables
0.012
(lb
ai/
1000
ft2)
1
0.012
3431.4
2916666.7
3427.3
Vegetables/
Ornamentals
0.023
(lb
ai/
1000
ft2)
1
0.023
1790.3
1521739.1
1788.2
Vegetables
0.047
(lb
ai/
1000
ft2)
1
0.047
876.1
744680.9
875.1
Average
Study
Use
Rate
0.26
(lb
ai/
1000
ft2)
1
0.26
158.4
134615.4
158.2
Fire
Ant
0.0075
(lb
ai/
gal
spray)
100
0.75
54.9
46666.7
54.8
4
Garden:
Low
Pressure
Handwand
(MRID
444598
01)
General
Use
(2%
soln)
0.02
(lb
ai/
gal
spray
applied)
5
0.1
368.4
77777.8
366.7
Perimeter
Nuisance
Pest
0.19
(lb
ai/
1000
ft2)
1
0.19
193.9
40935.7
193.0
Vegetables
0.012
(lb
ai/
1000
ft2)
1
0.012
3070.2
648148.1
3055.7
Vegetables/
Ornamentals
0.023
(lb
ai/
1000
ft2)
1
0.023
1601.8
338164.3
1594.3
Vegetables
0.047
(lb
ai/
1000
ft2)
1
0.047
783.9
165484.6
780.2
Average
Study
Use
Rate
0.083
(lb
ai/
1000
ft2)
1
0.083
443.9
93708.2
441.8
Fire
Ant
0.0075
(lb
ai/
gal
spray)
5
0.0375
982.5
207407.4
977.8
TABLE
11
CARBARYL
NONCANCER
MOEs
ATTRIBUTABLE
TO
COMBINED
SHORT
TERM
HOMEOWNER
HANDLER
DERMAL
AND
INHALATION
EXPOSURES
SCEN.
SCEN.
DESCRIPTOR
CROP
TYPE
OR
TARGET
EXPOSURE
FACTORS
DERMAL
MOEs
INHALATION
MOEs
COMBINED
MOEs
APPL.
RATE
(lb
ai/
unit)
BASIS
FOR
RATE
(defines
unit
treated)
TREATED
UNITS
ACTIVE
USED
(lb
ai/
event)
51
5
Trees/
Ornamentals:
Low
Pressure
Handwand
(MRID
445185
01)
Ornamental
0.023
(lb
ai/
1000
ft2)
1
0.176
1087.0
468227.4
1084.4
Pome
Fruit
0.07
(lb
ai/
1000
ft2)
1
0.07
357.1
153846.2
356.3
Nuts/
Stone
Fruit
0.12
(lb
ai/
1000
ft2)
1
0.12
208.3
89743.6
207.9
Citrus
0.176
(lb
ai/
1000
ft2)
1
0.023
142.0
61188.8
141.7
Average
Study
Use
Rate
0.0047
(lb
ai/
gal,
17g
ai/
4
min
at
2GPM)
5
0.024
1063.8
458265.1
1061.4
6
Trees/
Ornamentals:
Hose
End
Sprayer
(MRID
445185
01)
Ornamental
0.023
(lb
ai/
1000
ft2)
1
0.176
1560.8
1217391.3
1558.8
Pome
Fruit
0.07
(lb
ai/
1000
ft2)
1
0.07
512.8
400000.0
512.2
Nuts/
Stone
Fruit
0.12
(lb
ai/
1000
ft2)
1
0.12
299.1
233333.3
298.8
Citrus
0.176
(lb
ai/
1000
ft2)
1
0.023
204.0
159090.9
203.7
Average
Study
Use
Rate
0.005
(lb
ai/
gal
spray)
100
0.5
71.8
56000.0
71.7
7
Garden:
Backpack
Sprayer
(PHED)
General
Use
(2%
soln)
0.02
(lb
ai/
gal
spray
applied)
5
0.1
2745.1
23333.3
2456.1
Perimeter
Nuisance
Pest
0.19
(lb
ai/
1000
ft2)
1
0.19
1444.8
12280.7
1292.7
Vegetables
0.012
(lb
ai/
1000
ft2)
1
0.012
22875.8
194444.4
20467.8
Vegetables/
Ornamentals
0.023
(lb
ai/
1000
ft2)
1
0.023
11935.2
101449.3
10678.9
Vegetables
0.047
(lb
ai/
1000
ft2)
1
0.047
5840.6
49645.4
5225.8
Average
Study
Use
Rate
0.083
(lb
ai/
1000
ft2)
1
0.083
3307.3
28112.5
2959.2
Fire
Ant
0.0075
(lb
ai/
gal
spray)
5
0.0375
7320.3
62222.2
6549.7
8
Lawn
Care:
Hose
End
Sprayer
(MRID
449722
01/
ORETF
OMA
004)
Lawn
(broadcast)
0.25
(lb
ai/
1000
ft2)
20
5
25.5
875.0
24.7
Lawn
(spot)
0.25
(lb
ai/
1000
ft2)
1
0.25
509.1
17500.0
494.7
9
Dusting
Dog
(MRID
444399
01)
Average
Study
Use
Rate
0.0026
(lb
ai/
dog)
1
0.0026
163.2
1076.9
141.7
Dog
(10%
&
½
of
2
lb)
0.1
(lb
ai/
dog)
1
0.1
4.2
28.0
3.7
Dog
(5%
&
½
of
2
lb)
0.05
(lb
ai/
dog)
1
0.05
8.5
56.0
7.4
10
Dogs:
Liquid
Application
Dog
(0.5%
&
½
of
6
oz)
0.001
(lb
ai/
dog)
1
0.001
14000000.0
No
Data
No
Data
11
Granular
&
Baits
Lawn
Care:
Belly
Grinder
Lawn
(spot)
0.21
(lb
ai/
1000
ft2)
1
0.21
60.6
5376.3
59.9
Lawn
(spot)
0.1
(lb
ai/
1000
ft2)
1
0.1
127.3
11290.3
125.9
12
Granular
&
Baits
Lawn
Care:
Push
Type
Spreader
(MRID
449722
01/
ORETF
OMA
003)
Lawn
(broadcast)
0.21
(lb
ai/
1000
ft2)
20
4.2
490.2
18315.0
477.4
Lawn
(broadcast)
0.1
(lb
ai/
1000
ft2)
20
2
1029.4
38461.5
1002.6
13
Granulars
&
Baits
By
Hand
Ornamentals
and
Gardens
0.21
(lb
ai/
1000
ft2)
1
0.21
15.5
713.8
15.2
14
Aerosol
Various
0.005
(0.5
%
ai
in
soln./
1
pt
can)
16
0.08
79.5
364.6
65.3
15
Collar
Dog
0.013
(16
%
ai
per
1.3
oz
collar)
1
0.013
10769230.8
No
Data
No
Data
TABLE
11
CARBARYL
NONCANCER
MOEs
ATTRIBUTABLE
TO
COMBINED
SHORT
TERM
HOMEOWNER
HANDLER
DERMAL
AND
INHALATION
EXPOSURES
SCEN.
SCEN.
DESCRIPTOR
CROP
TYPE
OR
TARGET
EXPOSURE
FACTORS
DERMAL
MOEs
INHALATION
MOEs
COMBINED
MOEs
APPL.
RATE
(lb
ai/
unit)
BASIS
FOR
RATE
(defines
unit
treated)
TREATED
UNITS
ACTIVE
USED
(lb
ai/
event)
52
16
Sprinkler
Can
(Source:
Scenario
6)
Ornamentals
(2%
Soln)
0.02
(2%
soln
used
ad
libitum)
5
0.1
359.0
280000.0
358.5
17
Ornamental
Paint
On
Ornamentals
(2%
Soln)
0.02
(2%
soln
used
ad
libitum)
1
0.02
304.3
12323.9
297.0
4.4.2.2
Residential
Handler
Cancer
Risks
Cancer
risks
were
calculated
by
comparing
the
Lifetime
Average
Daily
Dose
(LADD)
to
the
Q1*
(8.75
x
10
4
(mg/
kg/
day)
1
).
The
LADD
was
calculated
using
the
equation
below.
LADD
=
ADD
xTreatment
frequency
x
Working
duration
365
days/
year
Lifetime
Where:
LADD
=
Lifetime
Average
Daily
Dose
or
the
amount
as
absorbed
dose
received
from
exposure
to
a
pesticide
in
a
given
scenario
amortized
over
a
lifetime
(mg
pesticide
active
ingredient/
kg
body
weight/
day);
ADD
=
Average
Daily
Dose
or
the
amount
as
absorbed
dose
received
from
exposure
to
a
pesticide
in
a
given
scenario
on
a
daily
basis
(mg
pesticide
active
ingredient/
kg
body
weight/
day)
[Note:
Represents
inhalation
and
dermal
exposure
contributions,
dermal
component
has
been
calculated
with
a
12.7
%
absorption
factor
defined
in
a
rat
study.];
Treatment
Frequency
=
The
annual
frequency
of
an
application
by
an
individual
(days/
year);
Working
Duration
=
The
amount
of
a
lifetime
that
an
individual
spends
engaged
in
a
career
involving
pesticide
exposure
(years);
Lifetime
=
The
average
life
expectancy
of
an
individual
(years).
Cancer
risk
was
then
calculated
using
the
following
equation:
Risk
=
LADD
x
Q1*
Where:
Risk
=
Probability
of
excess
cancer
cases
over
a
lifetime
(unitless);
Lifetime
Average
Daily
Dose
=
The
amount
as
absorbed
dose
received
from
exposure
to
a
pesticide
in
a
given
scenario
over
a
lifetime
(mg
pesticide
active
ingredient/
kg
body
weight/
day,
also
referred
to
as
LADD);
and
Q1*
=
Quantitative
dose
response
factor
used
for
linear,
low
dose
response
cancer
risk
calculations
(mg/
kg/
day)
1
.
53
Table
12
presents
the
quantitative
risks
associated
with
each
scenario
considered
in
the
assessment.
For
all
but
one
scenario
(i.
e.,
treating
dogs
with
½
bottle
of
10
percent
dust
risk
is
1.09x10
6
),
cancer
risks
are
less
than
1x10
6
(most
are
in
the
10
8
or
10
10
range)
when
a
single
application
per
year
is
evaluated.
The
risk
associated
with
dusting
a
dog
should
also
be
taken
in
context
of
the
uncertainties
associated
with
cancer
risk
assessment.
In
effect,
this
value
is
1x10
6
.
This
table
also
includes
the
allowable
number
of
days
exposure
per
year.
There
are
5
scenarios
where
5
days
or
less
of
exposure
per
year
is
allowable.
These
results
should
be
considered
in
conjunction
with
the
use
and
usage
information
supplied
by
the
Aventis
Crop
Science
that
indicates
the
50
th
percentile
annual
frequency
of
use
is
between
1
and
2
uses
per
year
and
that
5
uses
per
year
is
at
the
84
th
percentile.
As
with
the
noncancer
risks,
the
use
of
dusts
in
gardens
and
for
pet
grooming
along
with
some
liquid
sprays
on
ornamentals
appear
to
be
the
most
problematic
scenarios.
[Note:
The
scenario
where
risks
are
still
of
concern
(i.
e.,
>1x10
6
)
is
highlighted
in
the
table.]
Cancer
risks
appear
to
be
less
of
concern
compared
to
noncancer
risks
for
all
corresponding
scenarios.
TABLE
12:
CARBARYL
CANCER
RISKS
ATTRIBUTABLE
TO
COMBINED
HOMEOWNER
HANDLER
DERMAL
AND
INHALATION
EXPOSURES
SCEN.
SCEN.
DESCRIPTOR
CROP
TYPE
OR
TARGET
EXPOSURE
FACTORS
CANCER
RISK
ALLOWED
DAYS/
YR
APPL.
RATE
(lb
ai/
unit)
BASIS
FOR
RATE
(defines
unit
treated)
TREATED
UNITS
ACTIVE
USED
(lb
ai/
event)
1
Garden:
Ready
to
Use
Trigger
Sprayer
(MRID
444598
01)
Vegetables/
Ornamentals
0.003
32
oz
bottle
0.126
%
(769
977)
0.25
0.00075
1.27e
10
>365
Vegetables/
Ornamentals
0.003
32
oz
bottle
0.126
%
(769
977)
0.5
0.0015
2.54e
10
>365
Vegetables/
Ornamentals
0.003
32
oz
bottle
0.126
%
(769
977)
1
0.003
5.08e
10
>365
Average
Study
Use
Rate
0.012
(lb
ai/
1000
ft2)
1
0.012
2.03e
09
>365
2
Garden/
Ornamental
Dust
(MRID
444598
01)
Vegetables/
Ornamentals
0.4
4
lb
bottle
10%
(239
1513)
0.25
0.1
4.81e
08
21
Vegetables/
Ornamentals
0.4
4
lb
bottle
10%
(239
1513)
0.5
0.2
9.62e
08
10
Vegetables/
Ornamentals
0.4
4
lb
bottle
10%
(239
1513)
1
0.4
1.92e
07
5
Average
Study
Use
Rate
0.079
(lb
ai/
1000
ft2)
1
0.079
3.80e
08
26
3
Garden:
Hose
End
(MRID
444598
01)
General
Use
(2%
soln)
0.02
(lb
ai/
gal
spray
applied)
100
2
2.11e
07
5
Perimeter
Nuisance
Pest
0.19
(lb
ai/
1000
ft2)
1
0.19
2.01e
08
50
Vegetables
0.012
(lb
ai/
1000
ft2)
1
0.012
1.27e
09
>365
Vegetables/
Ornamentals
0.023
(lb
ai/
1000
ft2)
1
0.023
2.43e
09
>365
Vegetables
0.047
(lb
ai/
1000
ft2)
1
0.047
4.97e
09
201
Average
Study
Use
Rate
0.26
(lb
ai/
1000
ft2)
1
0.26
2.75e
08
36
Fire
Ant
0.0075
(lb
ai/
gal
spray)
100
0.75
7.93e
08
13
4
Garden:
Low
Pressure
Handwand
(MRID
444598
01)
General
Use
(2%
soln)
0.02
(lb
ai/
gal
spray
applied)
5
0.1
1.18e
08
85
Perimeter
Nuisance
Pest
0.19
(lb
ai/
1000
ft2)
1
0.19
2.25e
08
45
Vegetables
0.012
(lb
ai/
1000
ft2)
1
0.012
1.42e
09
>365
Vegetables/
Ornamentals
0.023
(lb
ai/
1000
ft2)
1
0.023
2.72e
09
>365
Vegetables
0.047
(lb
ai/
1000
ft2)
1
0.047
5.56e
09
180
Average
Study
Use
Rate
0.083
(lb
ai/
1000
ft2)
1
0.083
9.82e
09
102
Fire
Ant
0.0075
(lb
ai/
gal
spray)
5
0.0375
4.44e
09
225
TABLE
12:
CARBARYL
CANCER
RISKS
ATTRIBUTABLE
TO
COMBINED
HOMEOWNER
HANDLER
DERMAL
AND
INHALATION
EXPOSURES
SCEN.
SCEN.
DESCRIPTOR
CROP
TYPE
OR
TARGET
EXPOSURE
FACTORS
CANCER
RISK
ALLOWED
DAYS/
YR
APPL.
RATE
(lb
ai/
unit)
BASIS
FOR
RATE
(defines
unit
treated)
TREATED
UNITS
ACTIVE
USED
(lb
ai/
event)
54
5
Trees/
Ornamentals:
Low
Pressure
Handwand
(MRID
445185
01)
Ornamental
0.023
(lb
ai/
1000
ft2)
1
0.176
4.01e
09
250
Pome
Fruit
0.07
(lb
ai/
1000
ft2)
1
0.07
1.22e
08
82
Nuts/
Stone
Fruit
0.12
(lb
ai/
1000
ft2)
1
0.12
2.09e
08
48
Citrus
0.176
(lb
ai/
1000
ft2)
1
0.023
3.06e
08
33
Average
Study
Use
Rate
0.0047
(lb
ai/
gal,
17g
ai/
4
min
at
2GPM)
5
0.47
4.09e
09
244
6
Trees/
Ornamentals:
Hose
End
Sprayer
(MRID
445185
01)
Ornamental
0.023
(lb
ai/
1000
ft2)
1
0.176
2.79e
09
359
Pome
Fruit
0.07
(lb
ai/
1000
ft2)
1
0.07
8.49e
09
118
Nuts/
Stone
Fruit
0.12
(lb
ai/
1000
ft2)
1
0.12
1.45e
08
69
Citrus
0.176
(lb
ai/
1000
ft2)
1
0.023
2.13e
08
47
Average
Study
Use
Rate
0.005
(lb
ai/
gal
spray)
100
0.025
6.06e
08
16
7
Garden:
Backpack
Sprayer
(PHED)
General
Use
(2%
soln)
0.02
(lb
ai/
gal
spray
applied)
5
0.1
1.66e
09
>365
Perimeter
Nuisance
Pest
0.19
(lb
ai/
1000
ft2)
1
0.19
3.15e
09
317
Vegetables
0.012
(lb
ai/
1000
ft2)
1
0.012
1.99e
10
>365
Vegetables/
Ornamentals
0.023
(lb
ai/
1000
ft2)
1
0.023
3.81e
10
>365
Vegetables
0.047
(lb
ai/
1000
ft2)
1
0.047
7.79e
10
>365
Average
Study
Use
Rate
0.083
(lb
ai/
1000
ft2)
1
0.083
1.38e
09
>365
Fire
Ant
0.0075
(lb
ai/
gal
spray)
5
0.0375
6.22e
10
>365
8
Lawn
Care:
Hose
End
Sprayer
(MRID
449722
01/
ORETF
OMA
004)
Lawn
(broadcast)
0.25
(lb
ai/
1000
ft2)
20
5
1.73e
07
6
Lawn
(spot)
0.25
(lb
ai/
1000
ft2)
1
0.25
8.64e
09
116
9
Dusting
Dog
(MRID
444399
01)
Average
Study
Use
Rate
0.0026
(lb
ai/
dog)
1
0.0026
2.82e
08
35
Dog
(10%
&
½
of
2
lb)
0.1
(lb
ai/
dog)
1
0.1
1.09e
06
1
Dog
(5%
&
½
of
2
lb)
0.05
(lb
ai/
dog)
1
0.05
5.43e
07
2
10
Dogs:
Liquid
Application
Dog
(0.5%
&
½
of
6
oz)
0.001
(lb
ai/
dog)
1
0.001
3.11e
13
>365
11
Granular
&
Baits
Lawn
Care:
Belly
Grinder
Lawn
(spot)
0.21
(lb
ai/
1000
ft2)
1
0.21
7.21e
08
14
Lawn
(spot)
0.1
(lb
ai/
1000
ft2)
1
0.1
3.43e
08
29
12
Granular
&
Baits
Lawn
Care:
Push
Type
Spreader
(MRID
449722
01/
ORETF
OMA
003)
Lawn
(broadcast)
0.21
(lb
ai/
1000
ft2)
20
4.2
8.97e
09
112
Lawn
(broadcast)
0.1
(lb
ai/
1000
ft2)
20
2
4.27e
09
234
13
Granulars
&
Baits
By
Hand
Ornamentals
and
Gardens
0.21
(lb
ai/
1000
ft2)
1
0.21
2.83e
07
4
14
Aerosol
Various
0.005
(0.5
%
ai
in
soln./
1
pt
can)
16
0.08
5.94e
08
17
15
Collar
Dog
0.013
(16
%
ai
per
1.3
oz
collar)
1
0.013
4.04e
13
>365
16
Sprinkler
Can
(Source:
Scenario
6)
Ornamentals
(2%
Soln)
0.02
(2%
soln
used
ad
libitum)
5
0.1
1.21e
08
82
17
Ornamental
Paint
On
Ornamentals
(2%
Soln)
0.02
(2%
soln
used
ad
libitum)
1
0.02
1.44e
08
69
55
4.4.3
Residential
Postapplication
Risk
Assessment
Carbaryl
uses
are
extremely
varied
and
include
home
gardens,
ornamentals,
turf
(golf
courses
and
lawns)
and
companion
animals
(e.
g.,
on
dogs
and
cats).
Carbaryl
also
has
more
limited
uses
that
were
considered
including
as
a
mosquito
adulticide
in
residential
areas
and
for
Ghost/
Mud
shrimp
control
in
Washington.
As
a
result,
a
wide
array
of
individuals
of
varying
ages
can
potentially
be
exposed
when
they
do
activities
in
areas
that
have
been
previously
treated
or
have
contact
with
treated
companion
animals.
The
residential
postapplication
risk
assessment
addresses
these
types
of
exposures.
The
risks
from
exposure
to
carbaryl
residues
postapplication
were
determined
for
the
following
populations:
1)
Residential
(homeowner)
Adults:
The
following
postapplication
scenarios
were
assessed:
residential
turf
(lawncare),
residential
turf
(after
mosquito
control),
swimming/
beach
activity
(oyster
bed
treatments),
golfing,
home
garden
exposure
to
deciduous
trees
and
home
garden
exposure
to
fruiting
vegetables.
Within
each
scenario,
ranges
of
exposure
were
evaluated
for
different
application
rates,
duration
of
exposure,
and
postapplication
activities
(e.
g.,
weeding,
harvesting).
2)
Toddlers
(3
year
olds):
Toddlers
were
selected
as
a
representative
population
for
turf
and
companion
animal
assessments.
Exposures
from
turf
were
evaluated
separately
for
lawncare
uses
and
after
mosquito
control.
Beach
activity
(oyster
bed
treatments)
was
also
evaluated.
Separate
risk
assessments
were
considered
individually
and
as
a
total
exposure
for
turf
dermal
exposure
and
hand
to
mouth,
object
to
mouth
and
soil
ingestion.
For
pet
uses
and
the
beach
play
assessments,
dermal
and
hand
to
mouth
exposures
were
considered
individually
and
as
a
total
exposure.
A
separate
assessment
was
done
for
toddlers
who
could
potentially
ingest
carbaryl
granules.
[Note:
Values
for
this
population
were
used
in
the
aggregate
risk
calculations
for
children
(1
to
6
years
old).]
3)
Youth
aged
children
(ages
10
to
12):
children
of
this
age
could
help
with
garden
maintenance
(deciduous
trees
and
fruiting
vegetables)
and
therefore
were
considered
for
activities
related
to
fruiting
vegetables
and
fruit
trees.
Data
and
Assumptions
A
series
of
assumptions
and
exposure
factors
served
as
the
basis
for
completing
the
residential
handler
risk
assessments,
as
described
below.
The
assumptions
and
factors
used
in
the
risk
calculations
are
consistent
with
current
Agency
policy
for
completing
residential
exposure
assessments
(i.
e.,
SOPs
For
Residential
Exposure
Assessment
and
related
documents).
°
Several
carbaryl
specific
studies
were
used
in
the
development
of
this
assessment
including
a
turf
transferable
residue
(TTR)
study
conducted
in
California,
Georgia,
and
Pennsylvania
at
8.17
lb
ai/
acre
(MRID
451143
01).
This
study
was
conducted
using
the
standard
ORETF
protocol.
The
Georgia
data
were
used
for
the
assessment
(all
were
similar).
Residue
transferability
observed
in
this
data
was
1.20
percent.
The
Agricultural
Reentry
Task
Force
(ARTF)
conducted
several
dislodgeable
foliar
residue
(DFR)
studies
with
carbaryl.
The
olive
pruning
(MRID
56
451751
02)
and
cabbage
weeding
(MRID
451917
01)
studies
were
used
in
the
home
garden
risk
assessments.
Aventis
Crop
Science
is
a
member
of
the
ARTF
so
there
are
no
data
compensation
issues
associated
with
the
use
of
these
data.
All
of
these
carbaryl
specific
studies
should
be
considered
high
quality
for
risk
assessment
purposes.
°
Two
other
studies
completed
by
the
Washington
State
Department
of
Ecology
were
used
for
completing
the
risk
assessment
for
the
oyster
bed
use.
These
studies
provided
water
and
sediment
concentration
data
in
Willapa
Bay
where
these
applications
occur.
°
Exposure
frequency
values
used
in
cancer
risk
assessments
for
adults
are
the
same
as
those
used
for
residential
handlers
(1
time
per
year).
However,
the
Agency
does
believe
that
there
are
higher
frequency
golfers
(i.
e.,
average
golfers
over
all
ages
play
18
rounds
year)
based
on
a
1992
report
(Golf
Course
Operations,
Cost
of
Doing
Business/
Profitability
by
the
Center
For
Golf
Course
Management).
The
number
of
exposure
days
per
year
has
also
been
calculated
for
all
postapplication
exposure
scenarios.
°
Several
models
and
published
data
sources
were
also
used
to
develop
the
risk
assessment.
These
include
papers
related
to:
deposition
from
mosquito
control
by
Dukes
et
al
from
Florida
A&
M
University
and
transference
of
residues
from
treated
pets
by
Boone
et
al
from
Mississippi
State
University.
The
Agency's
Standard
Operating
Procedures
For
Residential
Exposure
Assessment
were
the
primary
guidance
used
for
this
assessment.
Several
other
models
and
guidance
documents
were
also
used
including
the
Agency's
SWIMODEL
(for
swimmers
in
Willapa
Bay
after
oyster
bed
treatments);
AgDrift
V2.0
(for
risks
from
mosquito
control),
and
the
Risk
Assessment
Guidance
For
Superfund
or
RAGS
(for
dermal
exposures
during
beach
play
and
oyster
harvest).
Specific
information
from
the
mosquito
control
label
and
historical
information
for
oyster
bed
applications
were
also
used
to
complete
the
assessments
(e.
g.,
droplet
spectra
requirements
to
predict
deposition
from
aerial
treatments
during
mosquito
control).
°
The
Agency
calculates
total
exposures
to
individual
chemicals
when
it
is
likely
that
behaviors
could
occur
simultaneously
that
would
lead
to
the
overall
dose
for
the
exposed
population
of
concern.
The
Agency
has
added
together
risk
values
(i.
e.,
MOEs)
for
different
kinds
of
exposures
within
the
turf
(dermal,
hand
to
mouth,
object
to
mouth,
and
soil
ingestion)
and
pet
scenarios
(dermal
and
hand
to
mouth).
These
represent
the
standard
set
of
exposures
that
are
typically
added
together
when
chemicals
are
used
on
turf
or
on
pets
because
it
is
logical
they
can
co
occur.
°
Exposures
to
children
playing
on
treated
turf
as
well
as
adults
on
turf
(lawncare
and
golfing)
have
been
addressed
using
the
latest
Agency
approaches
for
this
scenario
including:
°
5
percent
of
the
application
rate
has
been
used
to
calculate
the
0
day
residue
levels
used
for
defining
risks
from
hand
to
mouth
behaviors,
measured
TTR
values
are
not
used
because
of
differences
in
transferability
versus
what
would
be
expected
during
hand
tomouth
behaviors;
57
°
20
percent
of
the
application
rate
has
been
used
to
calculate
the
0
day
residue
levels
used
for
defining
risks
from
object
to
mouth
behaviors,
measured
TTR
values
are
not
used
because
of
differences
in
transferability
versus
what
would
be
expected
during
hand
tomouth
behaviors,
a
higher
percent
transfer
has
been
used
for
object
to
mouth
behaviors
because
it
involves
a
teething
action
believed
to
be
more
analogous
to
DFR/
leaf
wash
sample
collection
where
20
percent
is
also
used;
°
the
measured
TTR
levels
quantified
in
MRID
451143
01
have
been
used
to
complete
the
dermal
exposure
calculations
as
the
0
day
transferability
was
>
1
percent
of
the
application
rate
for
the
short
and
intermediate
term
data
sources,
studies
where
transferability
is
less
than
1
percent
are
not
used
for
risk
assessment
purposes
because
the
transfer
coefficients
used
by
the
Agency
for
defining
exposures
are
based
on
Jazzercize
studies
in
which
TTR
values
were
measured
by
techniques
where
transferability
is
generally
in
the
1
to
5
percent
range
other
than
the
ORETF
roller
method
where
transferability
tends
to
be
lower;
°
short
and
intermediate
term
exposures
have
been
calculated
because
play
and
mouthing
behaviors
are
assumed
to
routinely
occur
daily
and
for
extended
periods
such
as
over
30
days,
carbaryl
residues
are
also
expected
to
be
present
based
on
residue
dissipation
data
(i.
e.,
slow
dissipation
rate);
°
in
cases
where
0
day
residues
have
been
calculated
based
on
application
rates
(i.
e.,
hand
object
to
mouth
residues
and
for
soil
dissipation),
dissipation
over
time
measured
in
the
TTR
study
(i.
e.,
slope
of
decay
curve)
has
been
used
to
predict
TTR
and
soil
levels
over
time,
carbaryl
residues
were
detectable
even
at
14
days
after
application
(i.
e.,
final
sampling
interval)
at
all
sites
in
the
TTR
studies
used
in
this
assessment,
at
14
days
average
residues
at
the
Georgia
and
Pennsylvania
study
sites
were
still
orders
of
magnitude
above
the
quantitation
limit,
this
indicates
that
predicted
residue
levels
for
extended
durations
should
be
considered
appropriate
based
on
the
empirical
data
(e.
g.,
critical
for
consideration
of
intermediate
term
exposures);
°
the
transfer
coefficients
used,
except
golfing,
are
those
presented
at
the
1999
Agency
presentation
before
the
FIFRA
Science
Advisory
Panel
that
have
been
adopted
in
routine
practice
by
the
Agency;
°
transfer
coefficients
have
been
adjusted
for
differences
between
short
and
intermediateterm
exposures;
°
adult
golfers
have
been
assessed
using
a
transfer
coefficient
of
500
cm
2
/hour
[Note:
The
Agency
is
currently
developing
a
policy
on
golfer
exposures
and
has
used
this
value
in
other
assessments];
°
3
year
old
toddlers
are
expected
to
weigh
15
kg;
°
hand
to
mouth
exposures
are
based
on
a
frequency
of
20
events/
hour
and
a
surface
area
per
event
of
20
cm
2
representing
the
palmar
surfaces
of
three
fingers;
°
saliva
extraction
efficiency
is
50
percent
meaning
that
every
time
the
hand
goes
in
the
mouth
approximately
½
of
the
residues
on
the
hand
are
removed;
°
object
to
mouth
exposures
are
based
on
a
25
cm
2
surface
area;
58
°
exposure
durations
are
expected
to
be
2
hours
based
on
information
in
the
Agency's
Exposure
Factors
Handbook
except
for
golfers
where
the
exposure
duration
for
an
18
hole
round
of
golf
is
4
hours
based
on
a
1992
report
(Golf
Course
Operations,
Cost
of
Doing
Business/
Profitability
by
the
Center
For
Golf
Course
Management);
°
soil
residues
are
contained
in
the
top
centimeter
and
soil
density
is
0.67
mL/
gram;
°
dermal,
hand
and
object
to
mouth,
and
soil
ingestion
are
added
together
to
represent
an
overall
risk
from
exposure
to
turf
while
granular
ingestion
is
considered
to
be
a
much
more
episodic
behavior
and
is
considered
separately
by
the
Agency;
and
°
children
of
various
ages
down
to
the
very
young
(e.
g.,
4
or
5
years
old)
are
currently
playing
golf,
the
Agency
recognizes
that
age
may
impact
exposures
because
of
changes
in
behavior
and
skin
surface
area
to
body
weight
ratios
but
has
not
yet
developed
a
quantitative
approach
for
calculating
their
risks.
°
Exposures
to
children
and
adults
working
in
home
gardens
have
been
addressed
using
the
latest
Agency
approaches
for
this
scenario
including:
°
youth
aged
children
are
considered
along
with
adults;
°
12
year
old
youth
are
expected
to
weigh
39.1
kg;
°
exposure
durations
are
expected
to
be
40
minutes;
°
Pre
Harvest
Intervals
(PHIs)
are
less
than
7
days
for
most
crops
with
some
as
long
as
28
days;
°
transfer
coefficients
for
youth
were
calculated
by
adjusting
the
appropriate
adult
transfer
coefficients
by
a
50%
factor
as
has
been
done
by
the
Agency
since
the
inception
of
the
SOPs
For
Residential
Exposure
Assessment;
°
the
updated
transfer
coefficients
specified
in
Agency
policy
003
described
above
in
the
occupational
risk
assessment
have
been
used
rather
than
those
currently
specified
in
the
SOPs
because
they
represent
more
refined
estimates
of
exposure
for
the
fruiting
vegetable
and
deciduous
tree
crop
groups,
these
crop
groups
have
been
used
in
the
SOPs
to
represent
home
garden
exposures;
°
the
combination
of
adjusting
transfer
coefficients
for
youth
aged
children
and
using
appropriate
body
weights
for
the
age
group
results
in
dose
levels
that
are
slightly
lower
than
that
of
adults
in
the
same
activity
(the
TC
reduction
and
body
weight
reduction
is
essentially
a
1:
1
ratio);
and
°
the
DFR
data
used
for
the
assessments
are
the
same
as
those
used
in
the
occupational
risk
assessment
for
the
selected
crop
groups.
°
Exposures
to
children
after
contact
with
treated
pets
have
been
addressed
using
the
latest
Agency
approaches
for
this
scenario
including:
°
only
toddlers
are
considered
because
their
exposures
are
thought
to
be
highest
(i.
e.,
they
are
considered
the
highest
exposed
population
by
the
Agency);
59
°
an
equilibrium
approach
based
on
a
single
child
"hug"
of
the
treated
animal
is
used
to
assess
dermal
exposure
as
described
in
the
1999
Agency
SAP
Overview
document
(i.
e.,
the
skin
loads
after
a
single
contact
with
the
treated
animal
and
additional
contacts
don't
proportionally
add
exposures),
the
surface
area
of
the
dermal
hug
is
based
on
a
toddler
skin
surface
area
and
typical
clothing;
°
residue
dissipation
is
5
percent
per
day
for
the
shampoo
and
dust
products
(based
on
data
from
J.
Chambers
at
Mississippi
State
University
on
other
pet
use
products);
°
the
transferability
of
residues
from
fur
is
20
percent;
°
the
active
lifetime
of
a
collar
is
expected
to
be
120
days
based
on
label
statements
which
was
used
by
the
Agency,
a
daily
emission
term
from
the
collar
of
0.000290
mg/
cm
2
/gram
ai/
day
is
also
based
on
measured
data
from
Mississippi
State
University
for
a
pet
collar;
°
risks
are
based
on
an
even
loading
of
residues
across
the
entire
surface
of
a
30
lb
dog
which
has
been
chosen
as
a
representative
animal,
the
animal
surface
area
was
calculated
using
(12.3*
Body
Weight
(g)
0.65
)
from
the
Agency's
1993
Wildlife
Exposure
Factors
Handbook
(i.
e.,
dog
surface
area
of
5986
cm
2
);
°
the
daily
frequency
of
hand
to
mouth
contact
with
dogs
is
40
events
per
day,
in
each
event,
the
palmar
surface
of
the
hands
(i.
e.,
20cm
2
/event)
is
placed
in
the
mouth
of
the
child
contributing
to
nondietary
ingestion
exposure;
and
°
the
Agency
is
currently
in
the
process
of
considering
revisions
in
its
methodologies
for
completing
risk
assessments
for
pet
products,
some
of
the
key
inputs
that
are
potentially
subject
to
modification
include
the
amount
of
residues
which
are
transferable
from
pet
fur,
defining
the
number
of
hand
to
mouth
events,
and
evaluating
the
emission
term
for
collars.
°
There
are
many
likely
studies
focused
on
carbaryl
in
the
published
literature
or
available
from
various
governmental
Agencies
because
it
is
so
widely
used.
For
example,
the
Agency's
Office
of
Research
and
Development
along
with
other
Agencies
have
funded
a
project
entitled
Pesticide
Exposure
in
Children
Living
in
Agricultural
Areas
along
the
United
States
Mexico
Border
Yuma
County,
Arizona.
Preliminary
results
of
this
study
indicate
that
carbaryl
residues
were
identified
in
the
dust
of
20
percent
of
the
152
houses
sampled
and
in
approximately
24
percent
in
25
samples
collected
in
6
schools
in
the
same
region.
At
this
point,
the
Agency
has
not
identified
any
data
from
the
literature
or
other
sources
that
would
alter
the
conclusions
of
this
risk
assessment.
As
more
data
become
available,
the
Agency
will
consider
the
information
in
efforts
to
refine
the
assessment
(i.
e.,
use
additional
information
to
alter
numeric
risk
estimates
or
to
characterize
existing
estimates
if
warranted).
With
regard
to
this
specific
example,
current
Agency
policy
is
not
to
use
house
dust
estimates
to
calculate
risks
because
of
a
lack
of
an
appropriate
exposure
model.
Also,
in
a
1995
study
conducted
by
the
Centers
For
Disease
Control
(Hill
et
al)
entitled
Pesticide
Residues
In
Urine
Of
Adults
Living
In
The
United
States:
Reference
Range
Concentrations,
1000
adults
were
monitored
via
urine
collection.
One
of
the
analytes
measured
in
that
study
(1
naphthol)
is
a
potential
metabolite
of
carbaryl
as
well
as
of
naphthalene
and
napropamide.
This
metabolite
was
identified
in
86
percent
of
the
1000
adults
monitored
where
the
mean
value
was
17
ppb
and
the
99
th
percentile
was
290
ppb.
These
values
were
not
used
quantitatively
in
the
risk
assessment
for
carbaryl
because
of
the
uncertainties
associated
with
them
such
as
the
exact
contribution
of
each
possible
compound
to
the
overall
60
levels
and
no
linked
exposure
information.
The
investigators
also
reported
results
for
(2
naphthol)
which
is
also
a
metabolite
of
naphthalene
and
indicated
a
common
source
of
exposure
because
1
naphthol
and
2
naphthol
levels
were
similar
based
on
a
Pearson
correlation
of
0.64
(P=
0.0001).
The
mean
for
2
naphthol
is
7.2
ppb
and
the
99
th
percentile
was
54
ppb.
The
Agency
instead
considers
them
a
qualitative
indicator
that
exposures
in
the
general
population
are
likely
to
occur.
°
Aventis
Crop
Science
has
completed
and
is
in
the
process
of
submitting
to
the
Agency
a
biomonitoring
study
of
individuals
in
residences
following
the
application
by
a
member
of
the
household
to
the
lawn
and
either
the
vegetable
garden
or
ornamental
flowers.
A
biomonitoring
study
of
field
workers
during
harvesting
and
hand
thinning
operations
in
apples
and
cherries
will
also
be
submitted
to
the
Agency.
Based
on
personal
communication
with
Aventis
Crop
Science
scientists,
preliminary
results
from
the
residential
biomonitoring
study
indicate
that
the
highest
percentiles
of
the
distribution
of
the
younger
children
in
the
homes
were
similar
to
those
predicted
in
the
Agency's
turf
risk
assessment
for
toddlers
that
are
intended
to
represent
the
higher
percentiles
of
the
exposure
distribution.
A
more
detailed
analysis
will
be
completed
upon
submission.
°
Aventis
Crop
Science
is
also
a
member
of
the
Residential
Exposure
Joint
Venture
which
is
a
group
of
companies
conducting
a
survey
of
homeowners
to
ascertain
how
consumer
pesticide
products
are
used
(e.
g.,
rate,
frequency,
pests,
etc.).
Also,
based
on
discussions
with
Aventis
Crop
Science,
an
analysis
of
these
data
is
expected
to
be
submitted
which
could
be
used
to
refine
the
exposure
estimates
in
this
assessment
because
the
amounts
of
carbaryl
used
per
homeowner
application
could
be
refined.
Preliminary
discussions
concerning
this
survey
also
indicate
Agency
estimates
are
in
the
range
of
those
observed
in
the
survey.
4.4.3.1
Residential
Postapplication
Exposure
and
Noncancer
Risks
Two
different
types
of
noncancer
risk
calculations
were
required
based
on
expected
exposure
durations,
i.
e.,
short
term
(
30
days)
and
intermediate
term
(30
days
up
to
several
months).
Intermediate
term
risks
were
calculated
in
a
postapplication
situation,
when
they
were
not
for
residential
handlers,
because
residue
dissipation
data
demonstrated
that
carbaryl
residues
persist
over
that
time
and
it
is
clear
that
the
behaviors
considered
as
the
basis
for
this
assessment
can
occur
routinely
over
extended
periods
of
time
thus
creating
a
potential
window
for
exposures
(e.
g.,
children
playing
outside
on
the
grass
is
expected
to
be
a
routine
activity).
Noncancer
risks
were
calculated
using
the
MOE
approach,
as
described
under
Section
4.4.2.
The
toxicological
endpoint
of
concern
and
target
MOE
for
short
term
and
intermediate
term
dermal
exposures
is
the
same
as
that
used
for
the
short
term
dermal
exposure
for
residential
handlers
(i.
e.,
NOAEL
of
20
mg/
kg
from
the
21
day
dermal
toxicity
study
in
the
rat
and
a
target
MOE
of
100).
The
endpoints
of
concern
and
target
MOE
for
short
term
and
intermediate
term
nondietary
ingestion
exposure
were
defined
in
the
rat
developmental
neurotoxicity
study
and
subchronic
neurotoxicity
studies,
respectively
(i.
e.,
NOAEL
of
1
mg/
kg/
day
defined
in
both
studies
with
a
target
MOE
of
100).
Several
different
types
of
calculations
were
used
in
this
assessment
to
reflect
the
varying
age
61
groups,
behaviors,
data,
and
activities
that
were
considered.
In
essence,
all
can
be
summarized
by
saying
that
a
source
of
some
sort
(e.
g.,
DFR
on
leaves)
comes
in
contact
with
a
person
as
they
are
doing
an
activity
(e.
g.,
harvesting
garden
plants).
Exposures
were
then
calculated
by
multiplying
the
source
concentration
by
some
factor
(e.
g.,
transfer
coefficient
for
fruit
harvesting)
and
the
duration.
All
of
the
calculations
are
explained
in
detail
in
the
Occupational
and
Residential
Exposure
Chapter
(281418).
Two
of
the
key
algorithms
are
presented
below
for
informational
purposes.
These
represent
the
predominant
types
of
exposures
considered
in
the
postapplication
assessment
(i.
e.,
dermal
and
hand
tomouth
Dermal
exposures
were
calculated
by
considering
the
potential
sources
of
exposure
in
the
environment,
which
represent
the
DFRs
on
garden
plants,
TTRs
on
lawns,
and
transferable
residues
on
treated
pets
using
the
following
equation.
It
should
also
be
noted
that
there
are
distinct
transfer
coefficients
for
different
activities
(e.
g.,
fruit
harvest
versus
lawncare).
DE(
t)
(mg/
day)
=
(TR(
t)
(µg/
cm
2
)
x
TC
(cm
2
/hr)
x
Hr/
Day)/
1000
(µg/
mg)
Where:
DE(
t)
=
Daily
exposure
or
amount
deposited
on
the
surface
of
the
skin
at
time
(t)
attributable
for
activity
in
a
previously
treated
area,
also
referred
to
as
potential
dose
(mg
ai/
day);
TR(
t)
=
Transferable
residues
that
can
either
be
dislodgeable
foliar
or
turf
transferable
residue
at
time
(t)
where
the
longest
duration
is
dictated
by
the
decay
time
observed
in
the
studies
(µg/
cm
2
);
TC
=
Transfer
Coefficient
(cm
2
/hour);
and
Hr/
day
=
Exposure
duration
meant
to
represent
a
typical
workday
(hours).
[Note:
For
pets,
the
TC
and
Hr/
day
terms
are
replaced
with
a
onetime
"hug"
scenario.]
Likewise,
nondietary
ingestion
from
hand
to
mouth
behaviors
also
consider
the
environmental
concentrations
and
the
mouthing
behaviors
of
children.
The
following
equation
describes
how
these
exposures
have
been
calculated.
Where:
D
=
dose
from
hand
to
mouth
activity
(mg/
day);
TR
=
Transferable
Residue
where
dissipation
is
based
on
TTR
study
and
the
0
day
value
is
based
on
the
5%
initial
transferability
factor
(µg/
cm
2
);
SE
=
saliva
extraction
factor
(%);
SA
=
surface
area
of
the
hands
(cm
2
);
Freq
=
frequency
of
hand
to
mouth
events
(events/
hour);
and
Hr
=
exposure
duration
(hours).
6
Maximum
rates
of
4
to
8
lb
ai/
acre
are
specified
for
different
pests.
There
is
one
carbaryl
label
with
a
turf
application
rate
of
11
lb
ai/
acre;
however,
based
on
the
information
from
the
registrant
at
the
SMART
meeting
and
the
TTR
study
(MRID
45334301),
the
maximum
rate
is
more
likely
to
be
8
lbs
ai/
acre.
In
addition,
risks
exceed
HED's
level
of
concern
at
8
lbs
ai/
acre.
62
The
(TR(
t))
input
may
represent
levels
on
a
single
day
after
application
in
the
case
of
short
term
risk
calculations.
For
intermediate
term
calculations,
30
day
average
concentrations
were
calculated
based
on
the
applicability
of
the
toxicology
data
(i.
e.,
intermediate
term
endpoint
is
applied
to
exposures
>30
days).
Adult
Short
term
MOEs
only
for
lawncare
(i.
e.,
heavy
yardwork)
exceed
the
Agency's
level
of
concern
on
the
day
of
application
(i.
e.,
43
to
88).
For
this
activity,
it
takes
1
and
5
days,
respectively
at
the
4
and
8
lb
ai/
acre
application
rates,
6
for
residues
to
dissipate
to
a
point
where
short
term
MOEs
are
$
100.
In
all
other
scenarios
considered,
short
term
MOEs
are
$
100
on
the
day
of
application.
These
other
scenarios
include
vegetable
gardening,
golfing,
tending
fruit
trees.
More
localized
exposures
that
occur
after
mosquito
control
or
from
exposures
associated
with
oyster
bed
treatments
are
also
included.
Intermediate
term
MOEs
were
calculated
using
30
day
average
exposures
and
the
dissipation
rate
for
carbaryl.
In
all
cases,
intermediate
term
MOEs
are
$
100.
Table
13
presents
the
postapplication
MOE
values
calculated
for
adults
after
lawn
and
home
garden
applications
of
carbaryl.
Table
13:
Summary
of
Carbaryl
Noncancer
Postapplication
Residential
MOEs
For
Adults
Scenario
Descriptor
Results
Short
term
MOE
on
Day
0
Days
Short
term
MOE
UF
Intermediateterm
MOE
Residential
Turf
(Lawncare)
Max
Rate
at
4
lb
ai/
A
88
1
842
Max
Rate
at
8
lb
ai/
A
43
5
412
Aerial
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
3700
231268
0
35463
2216454
Ground
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
7031
439409
0
67380
4211262
Golfing
Max
Rate
at
4
lb
ai/
A
1274
0
12297
Max
Rate
at
8
lb
ai/
A
624
0
6021
Aerial
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
53654
3353387
0
517764
32360224
Ground
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
101943
6371435
0
983751
61484426
Table
13:
Summary
of
Carbaryl
Noncancer
Postapplication
Residential
MOEs
For
Adults
Scenario
Descriptor
Results
Short
term
MOE
on
Day
0
Days
Short
term
MOE
UF
Intermediateterm
MOE
63
Home
Garden
(Deciduous
Tree)
Very
Low
Exposure
(propping)
17373
0
53139
Low
Exposure
(irrigation,
scout,
weed)
1737
0
5314
High
Exposure
(harvest,
prune,
train,
tie,
thin)
579
0
1771
Home
Garden
(Fruiting
Vegetable)
Low
Exposure
(irrigation,
scout,
thin,
weed)
1758
0
9468
Medium
Exposure
(irrigation,
scout)
1256
0
6763
High
Exposure
(harvest,
prune,
stake,
tie)
879
0
4734
Oyster
Beds
Oyster
Harvest
967137
0
2680745
Swimming
293651
0
No
Data
Youth
aged
children
(10
to
12
years
old)
were
only
considered
in
the
home
garden
scenarios
per
Agency
guidance.
Short
term
MOEs
for
these
children
were
similar
to
those
calculated
for
adults
in
that
they
were
$
100
for
all
of
the
gardening
scenarios
considered.
Intermediate
term
MOEs
were
calculated
using
30
day
average
exposures
and
the
dissipation
rate
for
carbaryl.
In
all
cases,
intermediate
term
MOEs
are
$
100.
Table
14
below
summarizes
the
postapplication
MOE
values
calculated
for
youth
home
garden
applications
of
carbaryl.
Table
14:
Summary
of
Carbaryl
Noncancer
Postapplication
Residential
MOEs
For
Youth
Aged
Children
Scenario
Descriptor
Results
Short
term
MOE
on
Day
0
Days
Short
term
MOE
UF
Intermediateterm
MOE
Home
Garden
(Deciduous
Tree)
Very
Low
Exposure
(propping)
19408
0
59364
Low
Exposure
(irrigation,
scout,
weed)
1941
0
5936
High
Exposure
(harvest,
prune,
train,
tie,
thin)
647
0
1979
Table
14:
Summary
of
Carbaryl
Noncancer
Postapplication
Residential
MOEs
For
Youth
Aged
Children
Scenario
Descriptor
Results
Short
term
MOE
on
Day
0
Days
Short
term
MOE
UF
Intermediateterm
MOE
64
Home
Garden
(Fruiting
Vegetable)
Low
Exposure
(irrigation,
scout,
thin,
weed)
1964
0
10577
Medium
Exposure
(irrigation,
scout)
1403
0
7555
High
Exposure
(harvest,
prune,
stake,
tie)
982
0
5289
Toddler
(3
year
old)
exposures
were
considered
for
a
variety
of
scenarios
as
described
above
including
play
on
treated
turf,
play
with
treated
pets,
after
mosquito
control,
and
after
oyster
bed
treatments.
Ingestion
of
granules,
which
is
considered
a
highly
episodic
event
by
the
Agency
is
also
described
below.
The
results
from
all
scenarios
considered
are
presented
below
in
Table
15.
Short
term
MOEs
from
exposure
to
treated
turf
(in
products
labeled
for
direct
application
to
turf)
were
<100
on
the
day
of
application
for
both
rates
considered
(i.
e.,
4
and
8
lb
ai/
acre).
In
fact,
shortterm
MOEs
from
individual
pathways
were
not
$
100
for
any
turf
scenario
considered
on
the
day
of
application
except
for
the
soil
ingestion
component
of
the
turf
assessment
which
is
a
very
minor
contributor
to
overall
exposures.
As
a
reminder,
dermal,
hand
to
mouth,
and
object
to
mouth
exposures
pathways
were
considered
along
with
soil
ingestion.
Total
short
term
MOEs
(all
pathways)
were
$
100
at
the
lower
4
lb
ai/
acre
application
rate
14
days
after
application
and
18
days
at
the
higher
8
lb
ai/
acre
application
rate.
Dermal
and
hand
to
mouth
exposures
were
the
key
contributors
while
soil
ingestion
was
a
minor
contributor
to
the
total
MOE
estimates.
Intermediate
term
MOEs
were
calculated
using
30
day
average
exposures
and
the
dissipation
rate
for
carbaryl.
For
both
rates,
intermediate
term
MOEs
were
<100.
Exposures
to
toddlers
were
also
considered
after
application
of
carbaryl
as
a
mosquito
adulticide.
The
risks
are
presented
along
with
the
turf
use
risks
because
the
methods
are
similar
except
that
mosquito
control
calculations
also
account
for
deposition
from
aerial
and
ground
foggers.
Regardless
of
how
applications
are
made
(i.
e.,
by
ground
or
air),
both
short
term
MOEs
on
the
day
of
application
and
intermediate
term
MOEs
were
$
100.
The
assessments
for
pet
uses
considered
dermal
and
nondietary
ingestion
exposures
and
also
calculated
total
MOEs.
Short
term
MOEs
for
pet
uses
were
<100
even
30
days
after
application
regardless
of
whether
the
formulation
used
was
a
dust,
liquid
or
collar.
This
trend
was
observed
for
each
separate
exposure
pathway
as
well
as
the
total
MOE
estimates.
Hand
to
mouth
and
dermal
exposures
are
approximately
equal
contributors
to
the
overall
estimates
for
each
product
type.
The
results
are
similar
for
the
intermediate
term
MOEs
for
each
scenario.
There
is
one
pet
use
which
is
also
considered
to
be
a
chronic
exposure
by
the
Agency.
Pet
collars
are
assumed
to
be
worn
all
of
the
time
so
chronic
exposure
can
potentially
occur.
The
chronic
MOE
for
pet
collars
mirrors
the
short
and
intermediate
term
results.
The
assessments
for
beach
play
for
toddlers
after
oyster
bed
treatment
considered
dermal
and
65
nondietary
ingestion
exposures
and
also
calculated
total
MOEs.
Short
term
MOEs
were
>100
even
if
the
highest
monitored
sediment
concentration
value
from
any
study
available
to
the
Agency
was
used
as
the
basis
for
the
calculations.
The
intermediate
term
results
were
similar.
Table
15:
Summary
of
Carbaryl
Noncancer
Postapplication
Residential
Aggregate
MOEs
For
Toddlers
Scenario
Descriptor
Results
Short
term
MOE
on
Day
0
Days
For
Short
term
MOE
UF
Intermediateterm
MOE
Chronic
MOE
Pet
Treatments
Liquids
2.0
+30
4
NA
Dusts
0.
02
+30
0.04
NA
Collars
18
+30
18
43
Residential
Turf
(High
Activity)
Max
Rate
at
4
lb
ai/
A
11
14
91
NA
Max
Rate
at
8
lb
ai/
A
5
18
45
NA
Aerial
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
448
27983
0
3826
239095
NA
Ground
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
851
53167
0
7269
454280
NA
Oyster
Beds
Beach
Play
29532
0
81859
NA
Ingestion
of
carbaryl
granules
is
also
a
potential
source
of
exposure
because
children
can
eat
them
if
they
are
found
in
treated
lawns
or
gardens.
This
scenario
is
considered
to
be
an
episodic
in
nature.
Therefore,
acute
dietary
endpoints
are
always
used.
The
concentration
of
carbaryl
in
granular
products
ranges
generally
from
2
to
10
percent.
If
this
information
is
coupled
with
the
body
weight
of
a
toddler
(15
kg),
the
NOAEL
of
1
mg/
kg/
day
for
short
term
assessments
(which
is
also
the
same
value
used
for
the
aPAD),
and
the
uncertainty
factor
of
100
the
amount
of
formulation
that
can
be
consumed
at
the
uncertainty
factor
MOE
level
can
be
calculated.
The
Agency
generally
presents
these
results
based
on
the
number
of
carbaryl
granules
that
can
be
ingested.
However,
the
number
of
homeowner
formulations
is
extensive
and
impossible
to
characterize
in
that
much
detail
so
a
general
weight
estimate
is
presented.
If
a
2
percent
formulation
is
ingested,
7.5
mg
represents
exposure
at
an
MOE
of
100
(i.
e.,
1.6
x
10
5
lb).
If
a
10
percent
formulation
is
ingested,
1.5
mg
represents
exposure
at
an
MOE
of
100
(i.
e.,
3.3
x
10
6
lb).
For
illustrative
purposes,
if
one
considers
a
2
percent
formulation
and
the
density
of
soil
(0.67
mL/
gram,
many
granulars
are
clay
based),
only
0.005
mL
of
formulation
would
need
to
be
ingested
to
have
a
risk
concern
(i.
e.,
7.5
mg
*
1g/
1000mg
*
0.67
mL/
gram).
Note
that
this
volume
is
66
orders
of
magnitude
less
than
a
teaspoon
of
granular
formulation
(i.
e.,
0.1%
of
a
teaspoon
where
a
tsp.
=
5
mL).
4.4.3.2
Residential
Postapplication
Exposure
and
Risks
For
Cancer
Postapplication
cancer
risks
were
calculated
for
adults
only
considering
the
same
scenarios.
Risks
were
calculated
using
a
frequency
of
one
exposure
per
year
for
50
years.
Cancer
risks
were
calculated
using
a
linear
low
dose
extrapolation
approach
in
which
a
LADD
is
calculated
and
then
compared
with
a
Q1*
(8.75
x
10
4
(mg/
kg/
day)
1
),
as
described
in
Section
4.4.2.2.
The
number
of
days
of
exposure
per
year
under
a
ceiling
limit
of
cancer
risks
equal
to
1x10
6
was
also
calculated.
For
all
scenarios
on
turf,
cancer
risks
are
in
the
10
8
range
or
less
on
the
day
of
application
when
a
single
reentry
event
per
year
during
lawncare
activities
is
evaluated.
For
home
gardening,
golfing
or
from
mosquito
control,
risks
are
slightly
lower
in
the
10
9
to
10
12
range
when
a
single
reentry
event
per
year
is
evaluated
on
the
day
of
application.
Table
16
below
summarizes
the
postapplication
risk
values
calculated
for
adults
after
applications
of
carbaryl.
Risk
managers
should
consider
these
values
represent
a
single
reentry
day
into
a
treated
area
over
each
year
of
a
50
year
lifetime
on
the
day
of
application
and
that
the
Agency
lacks
data
to
link
the
annual
frequency
of
reentry
activity
to
residential
applications.
As
with
the
residential
handler
risks
above,
the
Agency
calculated
the
number
of
exposure
days
needed
to
reach
a
risk
level
of
1x10
6
for
each
scenario
on
the
day
of
application,
values
range
from
20
to
over
365
days
per
year
while
most
exceed
365
days
per
year.
Table
16:
Summary
of
Carbaryl
Postapplication
Residential
Cancer
Risks
For
Adults
Scenario
Descriptor
Results
Risk
on
Day
0
Allowed
Days/
Year
Residential
Turf
(Lawncare)
Max
Rate
at
4
lb
ai/
A
2.5
x
10
8
40
Max
Rate
at
8
lb
ai/
A
5.1
x
10
8
20
Aerial
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
9.5
x
10
12
to
5.9
x
10
10
>365
Ground
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
5.0
x
10
12
to
3.1
x
10
10
>365
Golfing
Max
Rate
at
4
lb
ai/
A
1.7
x
10
9
>365
Max
Rate
at
8
lb
ai/
A
3.5
x
10
9
287
Aerial
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
6.5
x
10
13
to
4.1
x
10
11
>365
Ground
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
3.4
x
10
13
to
2.1
x
10
11
>365
Table
16:
Summary
of
Carbaryl
Postapplication
Residential
Cancer
Risks
For
Adults
Scenario
Descriptor
Results
Risk
on
Day
0
Allowed
Days/
Year
67
Home
Garden
(Deciduous
Tree)
Very
Low
Exposure
(propping)
2.5
x
10
10
>365
Low
Exposure
(irrigation,
scout,
weed)
2.5
x
10
9
>365
High
Exposure
(harvest,
prune,
train,
tie,
thin)
7.5
x
10
9
133
Home
Garden
(Fruiting
Vegetable)
Low
Exposure
(irrigation,
scout,
thin,
weed)
2.5
x
10
9
>365
Medium
Exposure
(irrigation,
scout)
3.5
x
10
9
289
High
Exposure
(harvest,
prune,
stake,
tie)
4.9
x
10
9
202
Oyster
Beds
Oyster
Harvest
4.
5
x
10
12
>365
Swimming
6.1
x
10
12
>365
4.4.4
Residential
Risk
Characterization
Characterization
of
the
residential
risks
is
included
below
for
both
handlers
and
for
postapplication
exposures.
Residential
Handlers:
The
residential
handler
assessment
for
carbaryl
is
complex
in
that
calculations
were
completed
for
52
different
equipment
and
application
rate
scenarios.
Unlike
the
occupational
assessments,
only
short
term
exposures
were
considered
for
handlers
because
homeowner
use
patterns
are
not
believed
by
the
Agency
to
lead
to
intermediate
term
exposures
because
of
their
sporadic
nature.
Cancer
risks
were
also
calculated
using
a
linear,
low
dose
extrapolation
model
(i.
e.,
Q1*)
for
typical
residential
users
(1
event/
year).
Cancer
risks
were
also
considered
by
calculating
the
number
of
days
exposure
that
would
be
required
per
year
to
achieve
a
cancer
risk
of
1x10
6
to
illustrate
risk
levels
from
another
perspective.
All
totaled,
when
each
type
of
calculation
is
considered,
108
different
crop/
application
method
calculations
were
completed
for
residential
handlers.
The
data
that
were
used
in
the
in
the
carbaryl
residential
handler
assessment
represent
the
best
data
and
approaches
that
are
currently
available.
For
most
of
the
major
use
patterns,
carbaryl
specific
data
or
data
generated
by
the
Outdoor
Residential
Exposure
Task
Force
were
used.
These
data
generally
are
considered
to
be
high
quality
by
the
Agency
and
the
best
source
of
information
available
for
the
scenarios
where
they
were
used.
Carbaryl
specific
data
were
used
to
address
the
garden
and
68
tree/
ornamental
scenarios
with
several
types
of
equipment
and
formulations
including
liquid
trigger
sprayers,
dusts,
and
liquid
sprays
using
low
pressure
handwand
and
hose
end
sprayers.
Carbarylspecific
data
were
also
available
for
dusting
dogs.
The
ORETF
data
for
hose
end
sprayer
applications
to
turf
and
granular
applications
to
turf
were
also
used
to
address
those
scenarios.
In
the
remaining
scenarios,
the
Pesticide
Handlers
Exposure
Database
(PHED)
was
used
to
develop
the
unit
exposure
values.
The
quality
of
the
data
included
in
PHED
vary
widely
from
scenarios
that
meet
guideline
requirements
for
studies
to
others
where
a
limited
number
of
poor
quality
datapoints
are
available.
All
data
that
have
been
used
may
not
be
of
optimal
quality
but
represent
the
best
available
data.
The
inputs
for
application
rate
and
other
use/
usage
information
(e.
g.,
area
treated
and
frequency
of
use)
used
by
the
Agency
were
supported
by
the
available
carbaryl
labels
and
information
supplied
by
the
Aventis
Crop
Science
at
the
September
24,
1998
SMART
Meeting.
It
is
also
very
clear
that
because
carbaryl
is
such
as
widely
used
chemical
that
it
is
likely
every
potential
exposure
scenario
has
not
been
captured
because
of
difference
in
use
pattern.
As
more
refined
information
becomes
available
on
carbaryl
use,
the
Agency
will
refine
its
assessment
accordingly.
In
summary,
with
respect
to
residential
handler
risks,
the
Agency
believes
that
the
values
presented
in
this
assessment
represent
the
highest
quality
results
that
could
be
produced
given
the
exposure,
use,
and
toxicology
data
that
are
available.
However,
there
are
certain
elements
where
additional
data
are
required.
For
example,
it
is
difficult
to
ascertain
where
on
a
distribution
certain
input
values
may
fall
because
the
distributional
data
for
exposure,
application
rates,
acres
treated
and
many
other
parameters
are
unrefined.
Postapplication:
Like
the
residential
handler
assessment
discussed
above,
the
postapplication
residential
assessment
for
carbaryl
is
also
complex
in
that
noncancer
MOE
calculations
were
required
based
on
the
recently
selected
endpoints
along
with
cancer
risk
calculations
using
a
linear,
low
dose
extrapolation
model.
Carbaryl
residues
persist
in
the
environment
as
indicated
in
the
available
DFR
and
TTR
data
for
periods
where
intermediate
term
as
well
as
short
term
noncancer
risk
estimates
are
required.
Cancer
risks
were
calculated
only
for
adults
per
current
Agency
policy.
The
general
population
can
be
exposed
through
many
different
pathways
that
result
from
uses
on
lawns
and
turf,
in
gardens,
on
ornamental
plants,
and
from
treated
pets.
People
can
also
be
exposed
from
mosquito
adulticide
applications
and
uses
in
oyster
beds.
Carbaryl
labels
do
not
currently
allow
for
indoor
residential
uses
(e.
g.,
crack
and
crevice).
Settings
where
such
exposures
could
occur
would
include
around
personal
residences
and
in
other
areas
frequented
by
the
general
public
including
parks,
ball
fields,
and
playgrounds.
To
represent
the
wide
array
of
possible
exposures,
the
Agency
relies
on
the
scenarios
that
have
been
defined
in
the
SOPs
For
Residential
Exposure
Assessment
and
accompanying
documents
such
as
the
overview
presented
to
the
FIFRA
Science
Advisory
Panel.
For
turf
uses,
the
Agency
considered
adults
and
toddlers
(3
year
olds)
in
the
assessments.
Adult
activities
included
lawncare/
maintenance
and
also
golfing.
Toddler
MOEs
were
calculated
for
playing
on
turf
(using
exposure
data
from
the
Jazzercize
model)
and
also
addressed
nondietary
ingestion
(hand/
object
tomouth
and
soil
ingestion).
Exposures
from
tree
and
garden
uses
were
evaluated
by
considering
adults
and
youth
aged
children
(10
to
12
years
old)
doing
gardening
activities
such
as
weeding
and
harvesting
for
different
crop
groups.
Transfer
coefficients
from
the
fruiting
vegetable
crop
group
and
the
69
deciduous
tree
crop
group
were
used,
as
described
in
the
SOPs
For
Residential
Exposure
Assessment
to
represent
exposures
for
these
scenarios.
MOEs
from
treated
pets
were
evaluated
for
toddlers
again
for
whom
exposures
may
occur
from
dermal
contact
and
hand
to
mouth
behavior.
Adulticide
mosquito
applications
were
considered
by
first
defining
how
much
residues
are
deposited
on
the
ground
after
a
mosquito
control
application
then
using
the
same
methods
approaches
from
the
lawncare
assessment
to
address
adults
doing
heavy
yardwork
or
golfing
and
also
children
playing
on
treated
turf.
The
data
that
were
used
in
the
carbaryl
residential
postapplication
assessment
represent
the
best
data
and
approaches
that
are
currently
available.
To
the
extent
possible,
the
Agency
has
attempted
to
use
carbaryl
specific
data
such
as
with
the
dislodgeable
foliar
residue
(DFR)
data
used
for
the
garden
scenarios
and
the
turf
transferable
residue
(TTR)
data
used
for
the
dermal
component
of
the
turf
scenarios.
When
chemical
specific
data
were
unavailable,
the
Agency
used
the
current
approaches
for
residential
assessment,
many
of
which
include
recent
upgrades
to
the
SOPs.
For
example,
for
the
toddler
hand
to
mouth
calculations,
the
TTR
data
were
not
used
but
a
5
percent
transferability
factor
was
applied
to
calculate
residue
levels
appropriate
for
this
exposure
pathway.
Another
key
approach
to
consider
is
the
use
of
the
dermal
hug
approach
for
pet
products
which
was
proposed
at
the
September
1999
meeting
of
the
FIFRA
Science
Advisory
Panel.
Oyster
bed
uses
were
evaluated
based
on
guidance
from
Superfund
and
the
Agency's
SWIMODEL.
There
are
also
many
embedded
uncertainties
that
should
be
considered
in
the
interpretation
of
this
assessment
such
as
those
associated
with
the
use
of
Jazzercize
and
with
the
nondietary
ingestion
calculations.
Readers
should
consider
these
in
the
interpretation
of
the
overall
risk
estimates.
Readers
should
also
consider
the
screening
nature
of
the
SOPs
For
Residential
Exposure
Assessment
and
how
additional
data
could
refine
the
results.
Finally,
the
Agency
believes
that
the
values
presented
in
this
assessment
represent
the
highest
quality
results
that
could
be
produced
based
on
the
currently
available
postapplication
exposure
data.
Certainly
risk
managers
and
other
interested
parties
should
consider
the
quality
of
individual
inputs
when
interpreting
the
results
and
make
decisions
accordingly.
It
is
difficult
to
ascertain
where
on
a
distribution
the
values
which
have
been
calculated
fall
because
the
distributional
data
for
exposure,
residue
dissipation
and
many
other
parameters
are
unrefined.
The
Agency
does
believe,
however,
that
the
risks
represent
conservative
estimates
of
exposure
because
maximum
application
rates
are
used
to
define
residue
levels
upon
which
the
calculations
are
based.
Additionally,
estimates
are
thought
to
be
conservative
even
when
measures
of
central
tendency
(e.
g.,
most
transfer
coefficients
are
thought
to
be
central
tendency)
are
used
because
values
that
would
be
considered
to
be
in
the
lower
percentile
aspect
of
any
input
parameter
have
not
been
used
in
the
calculations.
There
are
many
studies
on
carbaryl
in
the
published
literature
or
available
from
various
governmental
Agencies
because
it
is
so
widely
used
that
can
be
used
to
inform
risk
managers
about
the
results
of
the
risk
assessment.
For
example,
the
Agency's
Office
of
Research
and
Development,
along
with
other
Agencies,
has
funded
a
project
entitled
Pesticide
Exposure
in
Children
Living
in
Agricultural
Areas
along
the
United
States
Mexico
Border
Yuma
County,
Arizona.
Preliminary
results
of
this
study
indicate
that
carbaryl
residues
were
identified
in
the
dust
of
20
percent
of
the
152
houses
sampled
and
in
approximately
24
percent
in
25
samples
collected
in
6
schools
in
the
same
region.
Also,
in
a
1995
study
conducted
by
the
Centers
For
Disease
Control
entitled
Pesticide
Residues
In
Urine
Of
Adults
Living
In
7
Hill
RH
et
al
(1995).
Pesticide
Residues
in
Urine
of
Adults
Living
in
the
United
States:
Reference
Range
Concentrations.
Environmental
Research
71:
99
108.
8
Pierce
JP
et
al
(1989).
Tobacco
Use
in
1986
Methods
and
Basic
Tabulations
from
Adult
Use
of
Tobacco
Survey.
U.
S.
Department
of
Health
and
Human
Services
Publication
Number
OM90
2004.
Office
on
Smoking
and
Health,
Rockville,
Maryland.
70
The
United
States:
Reference
Range
Concentrations,
7
1000
adults
were
monitored
via
urine
collection.
One
of
the
analytes
measured
in
that
study
(1
naphthol)
is
a
potential
metabolite
of
carbaryl
as
well
as
of
napthalene
and
napropamide.
This
metabolite
was
identified
in
86
percent
of
the
1000
adults
monitored
where
the
mean
value
was
17
ppb
and
the
99th
percentile
was
290
ppb.
These
values
were
not
used
quantitatively
in
the
risk
assessment
for
carbaryl
because
of
the
associated
uncertainties.
However,
the
results
from
both
studies
indicate
that
carbaryl
residues
are
present
in
areas
frequented
by
the
general
population
and
that
the
scenarios
which
consider
a
broad
range
of
exposures
are
reasonable.
4.4.5
Exposure
from
the
Use
of
Tobacco
Risks
from
carbaryl
residues
contained
in
tobacco
products
have
been
calculated
based
on
a
pyrolysis
study
in
tobacco.
In
assessing
exposure
through
use
of
tobacco,
HED
has
assumed
that
the
greatest
exposure
to
carbaryl
would
come
from
cigarettes.
Further,
HED
has
assumed
that
the
average
U.
S.
smoker
smokes
15
cigarettes
per
day.
8
Based
on
a
pyrolysis
study
submitted
by
the
registrant,
residues
of
carbaryl
total
approximately
44.58
ppm
in
combined
side
stream
and
main
stream
tobacco
smoke
(Memorandum
from
Thurston
Morton
dated
September
29,
1998,
D230407).
Since
this
is
a
composited
sample
of
main
stream
and
side
stream
smoke,
it
greatly
exaggerates
the
actual
exposure
to
the
smoker,
whose
primary
route
of
exposure
is
via
main
stream
smoke.
HED
further
assumes
that
100
percent
of
that
inhaled
is
absorbed
(i.
e.,
that
none
of
the
residue
is
exhaled
along
with
the
smoke).
These
assumptions
result
in
an
extreme
overestimate
of
actual
likely
exposure.
With
the
assumptions
regarding
residue
levels
and
smoking
frequency,
and
assuming
an
average
body
weight
of
70
kg,
HED
estimated
that
exposure
to
carbaryl
will
not
exceed
0.0096
mg/
kg/
day
[44.58
:
g/
g
cigarette
×
1
g/
cigarette
×
15
cigarettes/
day
×
1
mg/
1000
:
g
÷
70
kg
body
weight
=
0.0096
mg/
kg/
day].
The
short
term
inhalation
NOAEL
is
1
mg/
kg/
day
and
is
based
on
an
developmental
neurotoxicity
study
in
the
rat.
Based
on
the
inhalation
NOAEL,
the
short
term
MOE
for
carbaryl
exposure
from
the
use
of
tobacco
is
estimated
to
be
104
even
with
the
expectation
that
the
calculated
risks
are
an
extreme
overestimate.
The
residential
target
MOE
is
100.
The
Agency
has
not
examined
intermediate
or
long
term
exposure
to
carbaryl
via
tobacco
due
to
the
severity
and
quantity
of
health
effects
associated
with
the
use
of
tobacco
products.
4.4.6
Other
Residential
Exposures
This
assessment
for
carbaryl
reflects
the
Agency's
current
approaches
for
completing
residential
exposure
assessments
based
on
the
guidance
provided
in
the
Draft:
Series
875
Occupational
and
Residential
Exposure
Test
Guidelines,
Group
B
Postapplication
Exposure
Monitoring
Test
Guidelines,
the
Draft:
Standard
Operating
Procedures
(SOPs)
for
Residential
Exposure
Assessment,
and
the
9
There
are
several
aggregate
risk
guidance
documents
that
address
both
deterministic
and
probabilistic
risk
assessment
approaches.
The
major
science
policy
papers
are
available
at
www.
EPA.
Gov/
pesticides.
The
two
key
documents
used
for
this
assessment
are
1)
Updated
Interim
Guidance
For
Incorporating
Drinking
Water
Exposure
Into
Aggregate
Risk
Assessments
(Stasikowski,
8/
1/
99)
and
2)
HED
RARC
Format
and
Risk
Characterization
Guidance
(12/
22/
00).
71
Overview
of
Issues
Related
to
the
Standard
Operating
Procedures
for
Residential
Exposure
Assessment
presented
at
the
September
1999
meeting
of
the
FIFRA
Scientific
Advisory
Panel
(SAP).
The
Agency
is,
however,
currently
in
the
process
of
revising
its
guidance
for
completing
these
types
of
assessments.
Modifications
to
this
assessment
shall
be
incorporated
as
updated
guidance
becomes
available.
This
will
potentially
include
expanding
the
scope
of
the
residential
exposure
assessments
by
developing
guidance
for
characterizing
exposures
from
other
sources
already
not
addressed
such
as
from
spray
drift;
residential
residue
track
in;
exposures
to
farmworker
children;
and
exposures
to
children
in
schools.
5.0
AGGREGATE
RISK
ASSESSMENTS
AND
RISK
CHARACTERIZATION
Based
on
the
requirements
of
FQPA,
aggregate
risk
assessments
consider
combined
exposure
from
food,
water
and
residential
uses.
Different
types
of
aggregate
assessments
are
required
depending
upon
the
use
patterns
for
a
chemical,
the
types
of
toxic
effects
associated
with
it,
and
the
anticipated
durations
of
exposure.
A
series
of
aggregate
calculations
have
been
completed
for
carbaryl.
Section
5.1:
Calculation
of
Aggregate
Risks
and
DWLOCs
describes
how
these
values
have
been
determined.
Section
5.2:
Acute
Dietary
Aggregate
Risks
and
DWLOCs
presents
the
results
for
the
acute
dietary
only
assessment.
Section
5.3:
Chronic
Dietary
Aggregate
Risks
and
DWLOCs
presents
the
results
for
the
chronic
dietary
only
assessment.
Section
5.4:
Shortterm
Aggregate
Risks
and
DWLOCs
presents
the
results
for
the
short
term
assessment
which
includes
dietary
intake
and
residential
exposures.
Section
5.5:
Intermediate
term
Aggregate
Risks
and
DWLOCs
presents
the
results
for
the
intermediate
term
assessment
which
includes
dietary
intake
and
residential
exposures.
Section
5.6:
Aggregate
Cancer
Risks
and
DWLOCs
presents
the
results
for
the
cancer
assessment
that
includes
dietary
intake
and
residential
exposures.
Section
5.7:
Summary
of
Aggregate
Risks
provides
an
overview
of
the
aggregate
risk
assessment
results.
5.1
Calculation
of
Aggregate
Risks
and
DWLOCs
The
Agency
has
developed
several
guidance
documents
describing
the
mathematical
approaches
used
in
calculating
aggregate
risks,
the
theoretical
basis
for
these
calculations,
and
the
interpretation
of
the
Food
Quality
Protection
Act
that
requires
the
Agency
to
complete
these
kinds
of
calculations.
9
The
underlying
approach,
regardless
of
the
calculation
type,
is
the
same.
The
overall
risks
associated
with
a
specific
chemical
are
determined
by
its
hazard
database
and
its
associated
uncertainty
factors
or
negligible
risks
if
the
concern
is
cancer.
These
two
elements,
combined,
are
used
to
define
limits
for
the
amount
of
overall
exposures
an
individual
can
receive
from
the
chemical.
Once
these
limits
have
been
defined,
contributions
from
different
sources
of
exposure
are
added
together
to
see
if
the
aggregate
limit
is
exceeded.
The
approach
used
by
the
Agency
for
these
calculations
is
to
add
together
estimates
for
dietary
food
intake
and
residential
exposure
(not
used
for
acute
assessment
which
is
food
and
water
72
only)
then
subtract
this
from
the
exposure
limit
to
see
what
portion
of
the
limit
is
still
available,
if
any.
If
there
is
room
still
left
under
the
limit
(i.
e.,
dietary
and
residential
exposures
combined
do
not
exceed
the
exposure
limit),
then
drinking
water
exposures
are
considered
by
calculating
DWLOCs
(Drinking
Water
Levels
of
Concern).
If
there
is
no
room
left
under
the
limit
then
the
Agency
knows
the
overall
exposure
limit
has
been
exceeded
even
without
considering
drinking
water
intake
and
no
further
calculations
are
completed.
DWLOCs
represent
the
concentration
of
carbaryl
residues
in
drinking
water
that
cannot
be
exceeded
for
aggregate
exposures
to
exceed
the
overall
exposure
limit.
If
appropriate,
DWLOCs
are
calculated
by
defining
what
part
of
the
exposure
limit
has
not
been
taken
up
from
dietary
and
residential
exposures
which
in
turn
defines
the
maximum
amount
of
exposure
one
can
have
from
drinking
water.
This
can
be
a
very
simple
calculation
such
as
subtracting
acute
food
exposures
from
the
aPAD
or
chronic
food
intake
and
residential
LADD
estimates
from
the
Q1*
in
a
cancer
calculation.
In
some
cases
it
can
be
more
complex
such
as
for
the
short
term
assessment
that
required
using
the
1/
MOE
approach
described
above
in
Section
4.4.2.1:
Residential
Handler
Noncancer
Risks
where
water
and
dietary
MOEs
are
added
to
the
equation
and
compared
to
the
target
MOE.
The
equation
was
then
solved
for
the
water
MOE
which
was
in
turn
used
to
calculate
the
maximum
drinking
water
exposure
using
the
short
term
oral
NOAEL.
Maximum
allowable
drinking
water
exposure
levels
were
then
used
to
calculate
concentrations
in
water
based
on
standard
daily
consumption
estimates
and
body
weight
factors
for
different
subpopulations.
Adults
were
assumed
to
intake
2
liters
of
water
per
day
while
small
children
and
infants
were
assumed
to
intake
1
liter
of
water
per
day.
Standard
body
weights
were
also
used
(i.
e.,
10
kg
for
small
children,
60
kg
for
adult
females,
and
70
kg
for
other
adult
scenarios).
The
equation
used
to
calculate
the
DWLOCs
is
presented
below:
DWLOC(
µg/
L)
=
[water
exposure
(mg/
kg
bw/
day)
x
body
weight
(kg)]
[water
consumption
(L)
x
10
3
mg/
µg]
[Note:
Water
exposure,
body
weight,
and
consumption
inputs
are
specific
to
certain
exposure
durations,
toxicity
concerns,
and
populations
so
they
will
vary
from
assessment
to
assessment.]
Once
the
DWLOCs
have
been
calculated
they
were
then
compared
to
the
Estimated
Environmental
Concentrations
(EECs)
which
were
defined
by
the
Environmental
Fate
and
Effects
Division
(Section
4.3.3:
Modeling
EECs,
Table
10).
Drinking
water
sources
can
include
surface
water
or
groundwater.
EEC
values
were
calculated
for
both.
For
surface
water,
computer
modeling
with
the
EPA
PRZM3.12
and
EXAMS
2.97.7
programs
were
used
to
estimate
the
concentration
of
carbaryl
in
surface
water.
Index
reservoir
scenarios
corrected
for
Percent
Cropped
Area
(PCA)
for
representative
crops
were
used.
The
maximum
calculated
acute
and
chronic
EECs
(494
ppb
and
28
ppb,
respectively)
resulted
from
use
on
citrus
in
Florida.
In
this
case,
the
results
for
Florida
provided
the
highest
estimates;
however,
in
Florida
the
majority
of
drinking
water
is
derived
from
groundwater
(>
90%)
so
high
surface
water
concentrations
do
not
necessarily
indicate
high
exposure.
As
a
result,
both
Florida
and
the
results
for
Oregon
apples
have
been
considered
in
the
aggregate
assessment.
The
EECs
for
Oregon
apples
are
the
next
highest
values
for
both
the
acute
and
chronic
estimates
(144
and
9
ppb,
respectively).
Carbaryl
chemical
properties
are
outside
the
range
of
values
for
which
SCI
GROW
was
developed
(i.
e.,
aerobic
metabolism
is
faster
and
its
partition
coefficient
is
larger
which
equates
to
73
less
leaching
than
the
reference
compounds
both
factors
indicate
carbaryl
degrades
faster
than
the
reference
chemicals).
SCI
GROW
estimates
for
groundwater
EECs
may
not
predict
with
complete
accuracy,
maximum
levels
because
the
concentrations
calculated
are
90
day
averages.
It
is
possible;
therefore,
that
groundwater
concentration
peaks
could
not
be
identified.
Groundwater
levels
are
anticipated,
however,
to
be
more
stable
than
surface
water
concentrations.
If
the
EEC
is
less
than
the
corresponding
DWLOC
then
the
Agency
has
no
concerns
for
aggregate
risks
for
the
scenario.
If
EECs
exceed
the
DWLOC
then
aggregate
risks
are
of
concern.
For
carbaryl,
there
were
many
residential
scenarios
where
the
combined
MOEs
(i.
e.,
combinations
of
inhalation,
dermal
and
nondietary
ingestion
as
appropriate)
exceed
the
Agency's
risk
targets
making
the
calculation
of
DWLOCs
and
aggregate
risks
for
those
scenarios
inappropriate
because
exposure
limits
have
already
been
exceeded.
Additionally,
acute
dietary
risks
were
also
exceeded
for
infants
and
children
(1
to
6
years
old)
at
the
99.9
th
percentile
when
the
Carbamate
Market
Basket
Survey
(CMBS)
was
not
considered
in
the
assessment.
However,
the
risk
picture
could
substantively
change
if
residential
risks
are
refined
based
on
updated
use
information
from
the
carbaryl
survey
yet
to
be
submitted
to
the
Agency
and
the
Agency
chooses
to
regulate
using
the
results
of
the
CMBS.
Keeping
this
in
mind,
the
Agency
completed
DWLOC
and
aggregate
risk
calculations
for
illustrative
purposes
using
a
number
of
representative
exposure
scenarios
where
the
residential
and
dietary
risk
estimates
did
not
already
exceed
the
Agency's
level
of
concern.
For
example,
an
acute
assessment
with
CMBS
results
included
and
short
term
assessments
where
residential
handler
risks
weren't
already
of
concern
were
completed.
The
Agency
also
specifically
selected
some
scenarios
because
they
represent
major
residential
uses
(e.
g.,
garden
dusts)
or
specialized
low
exposure
scenarios
(e.
g.,
mosquito
control).
The
Agency
approach
for
calculating
aggregate
risks
using
different
sources
of
data
to
create
different
exposure
scenarios
for
illustrative
purposes
is
consistent
with
Agency
wide
guidance
for
exposure
assessment
and
risk
characterization
(e.
g.,
PDP
and
carbamate
market
basket
survey,
various
water
scenarios,
and
selected
residential
scenarios).
The
Agency
takes
this
approach
to
allow
for
more
informed
risk
management
decisions
that
consider
as
much
available
data
as
possible
along
with
the
uncertainties
associated
with
those
data.
For
example,
it
is
appropriate
to
present
results
based
on
both
PDP
and
the
carbamate
market
basket
survey.
PDP
data
are
routinely
used
in
Agency
risk
assessments
and
the
market
basket
study
is
of
sufficient
quality
for
incorporation
in
the
risk
assessment.
However,
there
are
uncertainties
associated
with
the
use
of
each
data
source
(e.
g.,
rubbing
of
fruit
prior
to
extraction
in
the
carbamate
market
basket
survey
which
may
decrease
residue
levels
as
described
above
in
Section
4.2).
74
5.2
Acute
Dietary
Aggregate
Risks
and
DWLOCs
The
results
of
the
acute
aggregate
risk
assessment
are
presented
below
in
Table
17.
These
calculations
are
based
on
the
use
of
the
Carbamate
Market
Basket
Survey
(CMBS).
Even
with
the
use
of
the
CMBS,
aggregate
risks
when
surface
water
is
the
source
of
drinking
water,
are
still
of
concern
for
all
infants,
children
(1
to
6
years
old)
and
children
(7
to
12
years
old)
regardless
of
whether
or
not
Florida
citrus
or
Oregon
apple
EECs
are
used
(i.
e.,
surface
water
is
not
a
major
drinking
water
source
in
Florida).
If
Florida
citrus
data
are
solely
considered,
aggregate
risks
are
of
concern
for
all
subpopulations.
Aggregate
risks
for
all
subpopulations
are
not
of
concern
if
groundwater
is
the
source
of
drinking
water.
[Note:
Most
DWLOCs
exceed
the
corresponding
EECs
for
groundwater
by
an
order
of
magnitude
or
greater.
This
should
be
considered
along
with
the
caution
that
it
is
possible
that
SciGrow
might
underestimate
groundwater
concentrations
for
carbaryl.]
Table
17:
Acute
DWLOC
Calculations
Based
on
Use
of
Carbamate
Market
Basket
Survey
Results
Population
Subgroup
aPAD
(mg/
kg/
day)
Acute
Food
Exp.
99.9th%
tile
(mg/
kg/
day)
Max.
Acute
Water
Exposure
(mg/
kg/
day)
Acute
DWLOC
(ug/
L
or
ppb)
EECs
Surface
Water
(all
PRZM/
EXMS)
Ground
Water
(SciGrow)
(ppb)
FL
Citrus
(ppb)
OR
Apples
(ppb)
All
Commodities
Using
1989
1992
CFSII
Consumption
Data
General
Population
0.
010000
0.004623
0.005377
188
494
144
0.8
All
Infants
0.
010000
0.007272
0.002728
27
494
144
0.8
Children
(1
6
yrs)
0.010000
0.007344
0.002656
27
494
144
0.8
Children
(7
12
yrs)
0.010000
0.006238
0.003762
38
494
144
0.8
Females
(13
50
yrs)
0.010000
0.003546
0.006454
194
494
144
0.8
Males
(13
19
yrs)
0.010000
0.002723
0.007277
255
494
144
0.8
Males
(20+
yrs)
0.010000
0.003423
0.006577
230
494
144
0.8
Seniors
(55+
yrs)
0.010000
0.004810
0.005190
182
494
144
0.8
All
Commodities
Using
1994
1998
CFSII
Consumption
Data
General
Population
0.
010000
0.004865
0.005135
180
494
144
0.8
All
Infants
0.
010000
0.008091
0.001909
19
494
144
0.8
Children
(1
6
yrs)
0.010000
0.009481
0.000519
5
494
144
0.8
Children
(7
12
yrs)
0.010000
0.004921
0.005079
51
494
144
0.8
Females
(13
50
yrs)
0.010000
0.004224
0.005776
173
494
144
0.8
Males
(13
19
yrs)
0.010000
0.004515
0.005485
192
494
144
0.8
Males
(20+
yrs)
0.010000
0.003359
0.006641
232
494
144
0.8
Seniors
(55+
yrs)
0.010000
0.004649
0.005351
187
494
144
0.8
Note:
For
characterization
purposes,
the
surface
water
EECs
for
Florida
citrus
exceed
exposure
limits
alone,
without
even
considering
food
intakes,
for
all
populations.
Additionally,
the
surface
water
EECs
for
Oregon
apples
exceed
exposure
limits
alone,
without
even
considering
food
intakes,
for
infants
and
children.
5.3
Chronic
Dietary
Aggregate
Risks
and
DWLOCs
The
results
of
the
chronic
aggregate
risk
assessment
are
presented
below
in
Table
18.
Chronic
aggregate
risks
were
not
of
concern
for
any
subpopulation
regardless
of
the
source
of
drinking
water,
even
considering
the
Florida
surface
water
EECs.
There
is
one
chronic
residential
exposure
scenario
associated
with
the
use
of
pet
collars
where
the
MOEs
for
children
are
of
concern.
As
such,
exposure
from
pet
collars
was
not
included
in
the
chronic
DWLOC
calculations
because
of
the
risk
concerns
for
this
scenario
and
to
illustrate
chronic,
aggregate
risks
for
all
others
who
are
not
exposed
to
collars.
75
Table
18:
Chronic
DWLOC
Calculations
Population
Subgroup
cPAD
(mg/
kg/
day)
Chronic
Food
Exposure
(mg/
kg/
day)
Max.
Chronic
Water
Exposure
(mg/
kg/
day)
Chronic
DWLOC
(ug/
L
or
ppb)
EECs
Surface
Water
(all
PRZM/
EXMS)
Ground
Water
(SciGrow)
(ppb)
FL
Citrus
(ppb)
OR
Apples
(ppb)
All
Commodities
Using
1989
1992
CFSII
Consumption
Data
General
Population
0.
010000
0.000032
0.009968
349
28
9
0.
8
All
Infants
0.
010000
0.000054
0.009946
100
28
9
0.
8
Children
(1
6
yrs)
0.010000
0.000057
0.009943
99
28
9
0.
8
Children
(7
12
yrs)
0.010000
0.000036
0.009964
100
28
9
0.
8
Females
(13
50
yrs)
0.010000
0.000026
0.009974
299
28
9
0.
8
Males
(13
19
yrs)
0.010000
0.000022
0.009978
349
28
9
0.
8
Males
(20+
yrs)
0.010000
0.000031
0.009969
349
28
9
0.
8
Seniors
(55+
yrs)
0.010000
0.000031
0.009969
349
28
9
0.
8
All
Commodities
Using
1994
1998
CFSII
Consumption
Data
General
Population
0.
010000
0.000035
0.009965
349
28
9
0.
8
All
Infants
0.
010000
0.000059
0.009941
99
28
9
0.
8
Children
(1
6
yrs)
0.010000
0.000074
0.009926
99
28
9
0.
8
Children
(7
12
yrs)
0.010000
0.000034
0.009966
100
28
9
0.
8
Females
(13
50
yrs)
0.010000
0.000028
0.009972
299
28
9
0.
8
Males
(13
19
yrs)
0.010000
0.000026
0.009974
349
28
9
0.
8
Males
(20+
yrs)
0.010000
0.000032
0.009968
349
28
9
0.
8
Seniors
(55+
yrs)
0.010000
0.000030
0.009970
349
28
9
0.
8
5.4
Short
term
Aggregate
Risks
and
DWLOCs
The
results
of
the
short
term
aggregate
risk
assessment
are
presented
below
in
Table
19.
The
exposure
scenarios
which
were
considered
in
this
assessment
represent
a
broad
range
of
carbaryl
uses.
The
only
scenarios
for
toddlers
that
were
included
were
for
the
mosquito
control
and
oyster
bed
uses.
The
Agency
has
risk
concerns
for
all
other
scenarios
that
were
addressed
for
toddlers
based
on
residential
exposures
alone
including
uses
on
turf
and
uses
on
pets
(see
Section
4.4.3.1:
Residential
Postapplication
Exposure
and
Noncancer
Risks).
In
the
residential
assessment,
youth
(ages
10
to
12)
were
also
considered
in
home
garden
scenarios.
The
risk
estimates
for
these
children
are
similar
to
that
for
adults
so
aggregate
risks
were
calculated
only
for
adults
with
the
stipulation
that
the
results
represent
both
populations
(i.
e.,
risks
are
actually
slightly
worse
for
adults).
For
adults,
the
following
postapplication
exposures
were
considered:
after
mosquito
control
(doing
heavy
yardwork/
lawncare);
golfing;
gardening
(highest
exposure
activity
tree
fruit
harvest);
and
oyster
harvesting.
Adults
doing
heavy
lawncare
tasks
after
normal
applications
to
turf
were
of
concern
for
residential
exposure
alone
so
they
were
not
considered
in
the
aggregate
assessment.
Additionally,
several
aggregate
assessments
for
homeowner
handlers
(most
at
average
application
rates)
were
completed
based
on
application
of
dusts
(gardens
and
pets):
hose
end
sprayer;
liquid
spray
spot
lawn
treatments;
and
broadcast
application
of
granulars
to
lawns.
The
handler
scenarios
are
numbered
and
these
correspond
to
the
residential
risk
assessment
scenario
numbers.
Risks
for
these
handler
scenarios
at
higher
application
rates
(e.
g.,
label
maximums)
were
of
concern
for
residential
exposure
alone
so
they
were
not
considered
in
the
aggregate
assessment.
All
calculations
for
adults
were
completed
for
both
women
and
men.
Results
were
similar
for
both
populations.
If
surface
water
EECs
based
on
Oregon
apples
or
groundwater
EECs
from
Sci
Grow
are
considered,
aggregate
risks
are
not
of
concern
for
the
selected
scenarios.
If
EECs
from
Florida
citrus
are
considered,
aggregate
risks
are
not
of
concern
for
the
selected
scenarios
except
for
application
of
dusts
76
to
gardens
at
the
average
rate
keeping
in
mind
that
surface
water
is
not
a
major
drinking
water
source
in
Florida.
[Note:
Most
DWLOCs
exceed
the
corresponding
EECs
for
groundwater
by
orders
of
magnitude.
This
should
be
considered
along
with
the
caution
that
it
is
possible
that
Sci
Grow
might
underestimate
groundwater
concentrations
for
carbaryl.]
Table
19:
Short
term
Aggregate
Risk
and
DWLOC
Calculations
Using
1989
1992
CFSII
Consumption
Data
Population
Subgroup
Target
Agg.
MOE
Food
MOE
Nondietary
Ing.
MOE
Dermal
MOE
Inhal.
MOE
Aggregat
e
MOE
Water
MOE
Allowable
Water
Exposure
(mg/
kg/
day)
DWLOC
(ug/
L
or
ppb)
EECs
Surface
Water
(all
PRZM/
EXMS)
Ground
Water
(SciGrow
)
(ppb)
FL
Citrus
(ppb)
OR
Apples
(ppb)
Postapplication
Children
Children
(1
6
yrs)
Aerial
Mosquito
Day
0
100
17544
562
2211
NA
437
130
0.007710
116
28
9
0.8
Children
(1
6
yrs)
Oyster
Bed
Day
0
100
17544
51681
68909
NA
11006
101
0.009909
149
28
9
0.8
Postapplication
Adult
Males
Adult
Male
Aerial
Mosquito
Day
0
Lawncare
100
32258
NA
3700
NA
3319
103
0.009699
340
28
9
0.8
Adult
Male
Golfing
Day
0
Max
Rate
100
32258
NA
624
NA
612
120
0.008366
293
28
9
0.8
Adult
Male
Garden
Day
0
High
Expo.
100
32258
NA
579
NA
569
121
0.008242
289
28
9
0.8
Adult
Male
Oyster
Bed
Use
Day
0,
Swim
100
32258
301815
10856944
NA
29065
100
0.009966
349
28
9
0.8
Adult
Male
Consumer
Product
Handlers
Adult
Male
Scen.
#2
Garden
Dust
Avg
Rate
100
32258
NA
120
1019
107
1580
0.000633
22
28
9
0.8
Adult
Male
Scen
#3
Gard.
Hose
End,
Avg
Rate
100
32258
NA
158
134615
157
274
0.003648
128
28
9
0.8
Adult
Male
Scen
#8
Lawn
Spot
Liquids
100
32258
NA
509
17500
487
126
0.007948
278
28
9
0.8
Adult
Male
Scen
#9
Dusting
Dog
Avg
Rate
100
32258
NA
163
1077
141
343
0.002913
102
28
9
0.8
Adult
Male/
Scen
#
12
Lawn
Broadcast
Granular
100
32258
NA
490
18315
470
127
0.007874
276
28
9
0.8
Postapplication
Adult
Females
Adult
Female
Aerial
Mosquito
Day
0
Lawncare
100
38462
NA
3700
NA
3375
103
0.009704
291
28
9
0.8
Adult
Female
Golfing
Day
0
Max
Rate
100
38462
NA
624
NA
614
119
0.008371
251
28
9
0.8
Adult
Female
Garden
Day
0
High
Expo.
100
38462
NA
579
NA
570
121
0.008247
247
28
9
0.8
Adult
Female
Oyster
Bed
Use
Day
0,
Swim
100
38462
301815
10856944
NA
34007
100
0.009971
299
28
9
0.8
Adult
Female
Consumer
Product
Handlers
Adult
Female
Scen.
#2
Garden
Dust
Avg
Rate
100
38462
NA
120
1019
107
1568
0.000638
19
28
9
0.8
Adult
Female
Scen
#3
Gard.
Hose
End,
Avg
Rate
100
38462
NA
158
134615
158
274
0.003653
110
28
9
0.8
Adult
Female
Scen
#8
Lawn
Spot
Liquids
100
38462
NA
509
17500
488
126
0.007953
239
28
9
0.8
Adult
Female
Scen
#9
Dusting
Dog
Avg
Rate
100
38462
NA
163
1077
141
343
0.002918
88
28
9
0.8
Adult
Female/
Scen
#
12
Lawn
Broadcast
Granular
100
38462
NA
490
18315
472
127
0.007879
236
28
9
0.8
5.5
Intermediate
term
Aggregate
Risks
and
DWLOCs
Separate
intermediate
term
aggregate
risk
and
DWLOC
calculations
were
not
completed
for
carbaryl
because
the
short
term
aggregate
risk
estimates
essentially
present
the
same
results
since
the
hazard
inputs
are
numerically
identical.
The
only
major
differences
would
be
the
postapplication
results
77
where,
instead
of
a
single
day
exposure
estimate,
the
exposures
represent
a
30
day
average.
The
DWLOCs
were
not
of
concern
for
the
short
term
exposure
scenarios
and
they
would
not
be
expected
to
be
of
concern
for
the
intermediate
term
scenarios
since
the
exposures
would
be
lowered
because
an
average
was
used
instead
of
a
single
day,
higher
exposure
estimate.
5.6
Aggregate
Cancer
Risks
and
DWLOCs
The
results
of
the
aggregate
cancer
risk
assessment
are
presented
below
in
Table
20.
The
exposure
scenarios
which
were
considered
in
this
assessment
represent
a
broad
range
of
carbaryl
uses.
The
same
scenarios
for
adults
were
considered
as
in
the
short
term
assessment
described
above
in
Section
5.4:
Short
term
Aggregate
Risks
and
DWLOCs.
Aggregate
cancer
risks
were
not
of
concern
for
any
subpopulation
regardless
of
the
source
of
drinking
water,
even
considering
the
Florida
surface
water
EECs.
Table
20:
Aggregate
Cancer
Risk
and
DWLOC
Calculations
Using
1989
1992
CFSII
Consumption
Data
Population
Subgroup
Q1*
(mg/
kg/
day)
1
Negligible
Risk
Level
Target
Maximum
Exposure
(mg/
kg/
day)
Chronic
Food
Exposure
(mg/
kg/
day)
Residential
Exposure
LADD
(mg/
kg/
day)
Aggregate
Cancer
Risk
(Food
&
Residential)
Maximum
Water
Exposure
(mg/
kg/
day)
DWLOC
(ug/
L
or
ppb)
EECs
Surface
Water
(all
PRZM/
EXMS)
Ground
Water
(SciGrow)
(ppb)
FL
Citrus
(ppb)
OR
Apples
(ppb)
Postapplication
Adult
Males
Adult
Male/
Aerial
Mosquito
Day
0
Lawncare
8.75x10
4
1.0x10
6
0.001143
0.000031
0.00000067
2.77E
008
0.001111
39
28
9
0.8
Adult
Male/
Golfing
Day
0
Max
Rate
8.75x10
4
1.0x10
6
0.001143
0.000031
0.00000400
3.06E
008
0.001108
39
28
9
0.8
Adult
Male/
Garden
Day
0
High
Expo.
8.75x10
4
1.0x10
6
0.001143
0.000031
0.00000857
3.46E
008
0.001103
39
28
9
0.8
Adult
Male/
Oyster
Bed
Use
Day
0,
Swim
8.75x10
4
1.0x10
6
0.001143
0.000031
0.00000001
2.71E
008
0.001112
39
28
9
0.8
Adult
Male
Consumer
Product
Handlers
Adult
Male/#
2
Garden
Dust
Avg
Rate
8.75x10
4
1.0x10
6
0.001143
0.000031
0.00004343
6.51E
008
0.001068
37
28
9
0.8
Adult
Male/#
3
Garden
Hose
End,
Avg
Rate
8.75x10
4
1.0x10
6
0.001143
0.000031
0.00003143
5.46E
008
0.001080
38
28
9
0.8
Adult
Male/#
8
Lawn
Spot
Liquids
8.75x10
4
1.0x10
6
0.001143
0.000031
0.00000987
3.58E
008
0.001102
39
28
9
0.8
Adult
Male/#
9
Dusting
Dog
Avg
Rate
8.75x10
4
1.0x10
6
0.001143
0.000031
0.00003223
5.53E
008
0.001080
38
28
9
0.8
Adult
Male/#
12
Lawn
Broadcast
Granular
8.75x10
4
1.0x10
6
0.001143
0.000031
0.00001025
3.61E
008
0.001102
39
28
9
0.8
Postapplication
Adult
Females
Adult
Female/
Aerial
Mosquito
Day
0
Lawncare
8.75x10
4
1.0x10
6
0.001143
2.6E
005
0.00000067
2.33E
008
0.001116
34
28
9
0.8
Adult
Female/
Golfing
Day
0
Max
Rate
8.75x10
4
1.0x10
6
0.001143
2.6E
005
0.00000400
2.63E
008
0.001113
33
28
9
0.8
Adult
Female/
Garden
Day
0
High
Expo.
8.75x10
4
1.0x10
6
0.001143
2.6E
005
0.00000857
3.03E
008
0.001108
33
28
9
0.8
Adult
Female/
Oyster
Bed
Use
Day
0,
Swim
8.75x10
4
1.0x10
6
0.001143
2.6E
005
0.00000001
2.28E
008
0.001117
34
28
9
0.8
Adult
Female
Consumer
Product
Handlers
Adult
Female/#
2
Garden
Dust
Avg
Rate
8.75x10
4
1.0x10
6
0.001143
2.6E
005
0.00004343
6.08E
008
0.001073
32
28
9
0.8
Adult
Female/#
3
Garden
Hose
End,
Avg
Rate
8.75x10
4
1.0x10
6
0.001143
2.6E
005
0.00003143
5.03E
008
0.001085
33
28
9
0.8
Adult
Female/#
8
Lawn
Spot
Liquids
8.75x10
4
1.0x10
6
0.001143
2.6E
005
0.00000987
3.14E
008
0.001107
33
28
9
0.8
Adult
Female/#
9
Dusting
Dog
8.75x10
4
1.0x10
6
0.001143
2.6E
005
0.00003223
5.10E
008
0.001085
33
28
9
0.8
Adult
Female/#
12
Lawn
Broadcast
Granular
8.75x10
4
1.0x10
6
0.001143
2.6E
005
0.00001025
3.17E
008
0.001107
33
28
9
0.8
78
5.7
Summary
of
Aggregate
Risks
In
many
residential
scenarios,
MOEs
exceed
the
Agency's
risk
targets
making
the
calculation
of
DWLOCs
and
aggregate
risks
for
those
scenarios
inappropriate
because
exposure
limits
have
already
been
exceeded.
Additionally,
acute
dietary
risks
were
also
exceeded
for
infants
and
children
(1
to
6
years
old)
at
the
99.9
th
percentile
when
the
Carbamate
Market
Basket
Survey
(CMBS)
was
not
considered
in
the
assessment.
However,
the
risk
picture
could
substantively
change
if
residential
risks
are
refined
based
on
updated
use
information
from
the
carbaryl
use
survey
yet
to
be
submitted
to
the
Agency
and
the
Agency
regulates
using
the
results
of
the
CMBS.
The
Agency
approach
for
calculating
aggregate
risks
using
different
sources
of
data
to
create
different
exposure
scenarios
for
illustrative
purposes
is
consistent
with
Agency
wide
guidance
for
exposure
assessment
and
risk
characterization
(e.
g.,
PDP
and
carbamate
market
basket
survey,
various
water
scenarios,
and
selected
residential
scenarios).
The
Agency
takes
this
approach
to
allow
for
more
informed
risk
management
decisions
that
consider
as
much
available
data
as
possible
along
with
the
uncertainties
associated
with
those
data.
For
example,
it
is
appropriate
to
present
results
based
on
both
PDP
and
the
carbamate
market
basket
survey.
PDP
data
are
routinely
used
in
Agency
risk
assessments
and
the
market
basket
study
is
of
sufficient
quality
for
incorporation
in
the
risk
assessment.
However,
there
are
uncertainties
associated
with
the
use
of
each
data
source
(e.
g.,
rubbing
of
fruit
prior
to
extraction
in
the
carbamate
market
basket
survey).
Keeping
this
in
mind,
the
Agency
completed
DWLOC
and
aggregate
risk
calculations
for
illustrative
purposes
using
a
number
of
representative
exposure
scenarios
where
the
residential
and
dietary
risk
estimates
did
not
already
exceed
the
Agency's
level
of
concern.
For
example,
an
acute
assessment
with
CMBS
results
included
and
short
term
assessments
where
residential
handler
risks
weren't
already
of
concern
were
completed.
The
highest
EECs
for
surface
water
were
from
Florida
citrus
but
most
drinking
water
in
Florida
is
from
groundwater.
Therefore,
results
from
surface
water
in
Florida
and
the
next
highest
values
(Oregon
apples)
were
considered
in
the
assessment.
The
acute
aggregate
assessment
indicates
that
even
with
the
use
of
the
Carbamate
Market
Basket
Survey
(CMBS),
aggregate
risks
when
surface
water
is
the
source
of
drinking
water,
are
still
of
concern
for
all
infants,
children
(1
to
6
years
old)
and
children
(7
to
12
years
old)
regardless
of
whether
or
not
Florida
citrus
or
Oregon
apple
EECs
are
used
(i.
e.,
surface
water
is
not
a
major
drinking
water
source
in
Florida).
If
Florida
citrus
results
are
solely
considered,
aggregate
risks
are
of
concern
for
all
subpopulations.
Surface
water
EECs
for
Florida
citrus
exceed
exposure
limits,
without
even
considering
food
intakes,
for
all
populations.
The
surface
water
EECs
for
Oregon
apples
exceed
exposure
limits
alone,
without
even
considering
food
intakes,
for
infants
and
children.
Acute
aggregate
risks
for
all
subpopulations
are
not
of
concern
if
groundwater
is
the
source
of
drinking
water.
Chronic
aggregate
risks
were
not
of
concern
for
any
subpopulation
regardless
of
the
source
of
drinking
water,
even
considering
the
Florida
surface
water
EECs.
In
the
short
term
assessment,
the
Agency
selected
representative
scenarios
where
residential
risks
alone
were
not
of
concern
including
mosquito
control,
oyster
harvesting,
golfing,
garden
harvest,
and
several
handler
scenarios
(all
at
average
rates,
max
rate
scenarios
were
of
concern
for
residential
exposures
alone).
If
surface
water
EECs
based
on
Oregon
apples
or
groundwater
EECs
from
SciGrow
are
considered,
aggregate
risks
are
not
of
concern
for
the
selected
scenarios.
If
EECs
from
Florida
citrus
are
considered,
aggregate
risks
are
not
of
concern
for
the
selected
scenarios
except
for
application
of
dusts
to
gardens.
Separate
intermediate
term
aggregate
risk
and
DWLOC
calculations
were
not
completed
for
carbaryl
because
the
short
term
aggregate
risk
estimates
essentially
presented
the
same
results
since
the
hazard
inputs
were
numerically
identical.
The
only
major
differences
would
be
the
postapplication
results
where,
instead
of
a
single
day
exposure
79
estimate,
the
exposures
represented
a
30
day
average.
Aggregate
cancer
risks
were
not
of
concern
for
any
subpopulation
regardless
of
the
source
of
drinking
water,
even
considering
the
Florida
surface
water
EECs.
6.0
CUMULATIVE
RISK
The
Food
Quality
Protection
Act
(1996)
stipulates
that
when
determining
the
safety
of
a
pesticide
chemical,
EPA
shall
base
its
assessment
of
the
risk
posed
by
the
chemical
on,
among
other
things,
available
information
concerning
the
cumulative
effects
to
human
health
that
may
result
from
dietary,
residential,
or
other
non
occupational
exposure
to
other
substances
that
have
a
common
mechanism
of
toxicity.
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
A
person
exposed
to
a
pesticide
at
a
level
that
is
considered
safe
may
in
fact
experience
harm
if
that
person
is
also
exposed
to
other
substances
that
cause
a
common
toxic
effect
by
a
mechanism
common
with
that
of
the
subject
pesticide,
even
if
the
individual
exposure
levels
to
the
other
substances
are
also
considered
safe.
Carbaryl
is
a
member
of
the
carbamate
class
of
pesticides.
This
class
also
includes
the
aldicarb,
methomyl
and
oxamyl
among
others.
HED
did
not
perform
a
cumulative
risk
assessment
as
part
of
this
reregistration
review
for
carbaryl
because
HED
has
not
yet
initiated
a
review
to
determine
if
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
carbaryl.
For
purposes
of
this
reregistration
decision,
EPA
has
assumed
that
carbaryl
does
not
have
a
common
mechanism
of
toxicity
with
other
substances.
The
registrant
must
submit,
upon
EPA's
request
and
according
to
a
schedule
determined
by
the
Agency,
such
information
as
the
Agency
directs
to
be
submitted
in
order
to
evaluate
issues
related
to
whether
carbaryl
shares
a
common
mechanism
of
toxicity
with
any
other
substance
and,
if
so,
whether
any
tolerances
for
carbaryl
need
to
be
modified
or
revoked.
If
HED
identifies
other
substances
that
share
a
common
mechanism
of
toxicity
with
carbaryl,
HED
will
perform
aggregate
exposure
assessments
on
each
chemical,
and
will
begin
to
conduct
a
cumulative
risk
assessment
once
the
final
guidance
HED
will
use
for
conducting
cumulative
risk
assessments
is
available.
HED
has
recently
developed
a
framework
that
it
proposes
to
use
for
conducting
cumulative
risk
assessments
on
substances
that
have
a
common
mechanism
of
toxicity.
This
guidance
reflects
recent
revisions
based
on
review
and
comment
from
earlier
guidance
issued
on
June
30,
2000
(65
FR
40644
40650)
that
is
available
from
the
OPP
Website
at:
http://
www.
epa.
gov/
fedrgstr/
EPAPEST
2000/
June/
Day
30/
6049.
pdf.
The
recently
revised
guidance
is
entitled
Guidance
on
Cumulative
Risk
Assessment
of
Pesticide
Chemicals
That
Have
A
Common
Mechanism
Of
Toxicity
(January
14,
2002).
In
the
guidance,
it
is
stated
that
a
cumulative
risk
assessment
of
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
will
not
be
conducted
until
an
aggregate
exposure
assessment
of
each
substance
has
been
completed.
Before
undertaking
a
cumulative
risk
assessment,
HED
will
follow
procedures
for
identifying
chemicals
that
have
a
common
mechanism
of
toxicity
as
set
forth
in
the
"Guidance
for
Identifying
Pesticide
Chemicals
and
Other
Substances
that
Have
a
Common
Mechanism
of
Toxicity"
(64
FR
5795
5796,
February
5,
1999).
HED
will
also
address
issues
described
in
the
document
entitled
80
Consideration
of
the
FQPA
Safety
Factor
and
Other
Uncertainty
Factors
In
Cumulative
Risk
Assessment
of
Chemicals
Sharing
a
Common
Mechanism
of
Toxicity
(Draft:
February
28,
2002).
7.0
OCCUPATIONAL
RISK
ASSESSMENT
This
section
of
the
risk
assessment
addresses
exposures
to
individuals
who
are
exposed
as
part
of
their
employment.
These
exposures
can
occur
because
people
have
contact
with
carbaryl
residues
while
using
commercial
products
containing
carbaryl
(i.
e.,
handlers)
or
by
being
in
areas
that
have
been
previously
treated
(postapplication
workers).
A
thorough
understanding
of
how
carbaryl
is
used
is
critical
to
the
development
of
a
quality
risk
assessment.
Because
this
information
is
also
critical
to
the
dietary
and
residential
exposure
assessments
presented
above,
available
use
information
has
already
been
summarized.
Please
refer
to
Section
4.1:
Summary
of
Registered
Uses
for
information
on
how
carbaryl
is
used.
All
calculations
for
occupationally
exposed
people
are
based
on
this
information.
Also,
for
more
detailed
information
pertaining
to
the
occupational
risk
calculations,
please
refer
to
the
Occupational
and
Residential
Exposure
Assessment
(D281418)
prepared
by
Jeff
Dawson.
The
document
D281418
contains
detailed
descriptions
of
the
data
used,
methods,
and
risks
calculated
for
each
scenario.
Section
7.1:
Occupational
Handler
Risk
Assessment
describes
the
data,
methods,
and
risk
results
(both
cancer
and
noncancer)
associated
with
the
use
of
commercial
products
which
contain
carbaryl.
Section
7.2:
Occupational
Postapplication
Risk
Assessment
describes
the
data,
methods,
and
risk
results
associated
with
exposures
to
workers
as
they
complete
activities
required
for
the
production
and
maintenance
of
crops
or
other
areas
such
as
turf
that
might
require
the
use
of
carbaryl.
Section
7.3:
Occupational
Risk
Characterization
provides
information
pertaining
to
the
quality
of
the
assessment
including
data
used,
uncertainties
with
the
methods,
and
any
other
information
that
might
be
used
to
describe
the
quality
of
the
results.
Section
7.4:
Human
and
Domestic
Animal
Incident
Data
Review
describes
the
analysis
conducted
by
Agency
epidemiologists.
7.1
Occupational
Handler
Risk
Assessment
The
Agency
completes
occupational
handler
risk
assessments
using
scenarios
as
the
basis
for
the
calculations
as
described
in
the
U.
S.
EPA
Guidelines
For
Exposure
Assessment.
For
commercial
pesticide
products,
the
Agency
categorizes
handler
exposures
based
on
the
kinds
of
formulations
(e.
g.,
liquids
or
various
solids),
the
kinds
of
equipment
used
to
make
applications
(e.
g.,
groundboom,
aerial,
or
airblast),
the
nature
of
the
task
(e.
g.,
mixing/
loading,
applying,
or
both
combined),
and
the
level
of
personal
protection
used.
Identifying
the
duration
of
exposure
is
also
a
critical
element
in
the
development
of
a
risk
assessment
to
ensure
that
the
proper
hazard
component
is
used.
For
carbaryl
uses,
the
Agency
identified
28
major
occupational
exposure
scenarios
based
on
the
types
of
equipment
and
techniques
that
potentially
can
be
used
for
carbaryl
applications.
Most
of
the
scenarios
were
classified
as
having
short
term
and
intermediate
term
exposures
(up
to
30
days
and
30
days
to
several
months,
respectively).
A
few
other
scenarios
have
also
been
addressed
that
are
thought
to
have
long
term
or
chronic
exposures
(several
months
to
every
working
day)
associated
with
them
in
the
greenhouse
and
floriculture
industry.
The
quantitative
exposure/
risk
assessment
developed
for
occupational
handlers
was
based
on
the
following
scenarios.
[Note:
The
numbers
correspond
to
the
tracking
system
included
in
D281418.]
81
Mixing/
Loading
(1a)
Dry
Flowable
for
Aerial/
Chemigation
in
Agriculture;
(1b)
Dry
Flowable
for
Airblast;
(1c)
Dry
Flowable
for
Groundboom;
(1d)
Dry
Flowable
for
High
Pressure
Handwand
and
Right
of
Way
Sprayers;
(1e)
Dry
Flowable
for
LCO
Applications;
(1f)
Dry
Flowable
for
Aerial
Wide
Area
Uses;
(2a)
Granular
for
Aerial;
(2b)
Granular
for
Broadcast
Spreader;
(3a)
Liquids
for
Aerial/
Chemigation;
(3b)
Liquids
for
Airblast;
(3c)
Liquids
for
Groundboom;
(3d)
Liquids
for
High
Pressure
Handwand
and
Right
of
Way
Sprayers;
(3e)
Liquids
for
LCO
Applications;
(3f)
Liquids
for
Aerial
Wide
Area
Uses;
(3g)
Liquids
for
Ground
Wide
Area
Uses;
(4a)
Wettable
Powder
for
Aerial/
Chemigation;
(4b)
Wettable
Powder
for
Airblast;
(4c)
Wettable
Powder
for
Groundboom;
(4d)
Wettable
Powder
for
High
Pressure
Handwand
and
Right
of
Way
Sprayers;
(4e)
Wettable
Powder
for
LCO
Applications;
(4f)
Wettable
Powder
for
Aerial
Wide
Area
Uses;
Applicator:
(5a)
Aerial/
Liquid
Application;
(5b)
Aerial/
Liquid
Wide
Area
Application;
(5c)
Aerial/
Granular
Application;
(6a)
Airblast
Application;
(6b)
Wide
Area
Ground
Fogger
(Airblast
as
surrogate);
(7)
Groundboom
Application;
(8)
Solid
Broadcast
Spreader
Application;
(9)
Aerosol
Can
Application;
(10)
Trigger
Sprayer
(RTU)
Application;
(11)
Right
of
Way
Sprayer
Application;
(12)
High
Pressure
Handwand
Application;
(13)
Veterinary
Technician/
Animal
Groomer
Liquid
Application;
(14)
Veterinary
Technician/
Animal
Groomer
Dust
Application;
(15)
Granulars/
Bait
and
Pellets
Dispersed
by
Hand;
(16)
Granulars/
Bait
and
Pellets
Dispersed
with
Spoon;
82
Mixer/
Loader/
Applicator:
(17)
Low
Pressure/
High
Volume
Turfgun
Application;
(18a)
Wettable
powder,
Low
pressure
handwand;
(18b)
Liquid:
Low
Pressure
Handwand;
(19)
Backpack;
(20)
Granular
Belly
Grinder;
(21)
Push
type
Granular
Spreader;
(22)
Handheld
Fogger;
(23)
Powered
Backpack;
(24)
Granular
Backpack;
(25)
Tree
Injection;
(26)
Drenching/
Dipping
Seedlings
For
Propagation;
(27)
Sprinkler
Can;
Flaggers:
(28a)
Flagging
For
Liquid
Sprays;
and
(28b)
Flagging
For
Granular
Applications.
For
each
of
these
scenarios,
risk
calculations
were
completed
based
on
eight
levels
of
personal
protection
that
were
defined
based
on
different
combinations
of
the
following:
1)
baseline
protection
(typical
work
clothing
or
a
long
sleeved
shirt
and
long
pants,
no
respiratory
protection
and
no
chemical
resistant
gloves);
2)
minimum
personal
protective
equipment
(baseline
scenario
with
the
use
of
chemical
resistant
gloves
and
a
dust/
mist
respirator
with
a
protection
factor
of
5);
3)
maximum
personal
protective
equipment
(baseline
scenario
with
the
use
of
an
additional
layer
of
clothing
(e.
g.,
a
pair
of
coveralls),
chemical
resistant
gloves,
and
an
air
purifying
respirator
with
a
protection
factor
of
10);
4)
engineering
controls
(use
of
an
appropriate
engineering
control
such
as
a
closed
tractor
cab
or
closed
loading
system
for
granulars
or
liquids).
Current
labels
mostly
require
single
layer
clothing,
chemical
resistant
gloves,
and
no
respirator.
Data
and
Assumptions
A
series
of
assumptions
and
exposure
factors
served
as
the
basis
for
completing
the
occupational
handler
risk
assessments,
as
described
below.
The
assumptions
and
factors
used
in
the
risk
calculations
are
consistent
with
current
Agency
policy
for
completing
occupational
exposure
assessments
(e.
g.,
PHED
Surrogate
Exposure
Guide
and
Exposac
Policy
9:
Standard
Values
For
Daily
Acres
Treated
In
Agriculture).
[Note:
PHED
is
a
database
that
contains
monitored
field
data
used
for
assessments.
See
Section
4.4.2
Residential
Handler
Risk
Assessment
above
for
further
information.]
83
°
Average
body
weight
of
an
adult
handler
is
70
kg
as
described
in
the
residential
handler
assessments
(see
Section
4.4.2).
°
Several
generic
protection
factors
were
used
to
calculate
handler
exposures.
The
protection
factors
used
for
clothing
layers
(i.
e.,
50%)
and
gloves
(90%)
have
not
been
completely
evaluated
by
the
Agency.
Additionally,
protection
factor
was
used
to
estimate
exposures
that
involve
engineering
controls
if
required
(98%).
The
values
used
for
respiratory
protection
(i.
e.,
PF
5
or
PF
10)
are
based
on
the
NIOSH
Respirator
Decision
Logic.
°
For
cancer
risk
calculations,
a
value
of
30
application
events
per
year
for
all
commercial
applicator
scenarios
and
10
days
per
year
to
account
for
private
growers
was
used.
These
values
are
supported
by
the
data
included
in
the
University
of
California
studies
of
seasonal
labor
in
California
and
the
recent
Department
of
Labor
National
Agricultural
Worker
Survey
(NAWS).
The
exposure
duration
values
used
by
HED
in
the
cancer
risk
assessment
are
consistent
with
those
used
for
other
chemicals
(i.
e.,
35
working
years
and
70
year
lifetime).
°
In
many
scenarios,
it
is
likely
that
a
grower
would
mix,
load,
and
apply
chemicals
all
in
one
day
because
of
limited
labor,
efficiency,
or
many
other
reasons.
In
most
cases,
mixing/
loading
and
application
are
considered
separate
job
functions
because
of
the
available
data
and
also
it
allows
for
more
flexibility
in
the
risk
management
phase
(e.
g.,
assigning
requirements
for
specific
types
of
protective
equipment).
°
Flagging
during
aerial
applications
has
been
addressed
even
though
it
may
be
limited
in
nature
(10
to
15%
of
aerial
application
operations).
Engineering
controls
(e.
g.,
Global
Positioning
Satellite
technology)
are
now
predominantly
used
by
pilots
as
indicated
by
the
1998
National
Agricultural
Aviation
Association
(NAAA)
survey
of
their
membership.
°
The
maximum
application
rates
allowed
by
labels
were
used
in
the
risk
assessments.
If
additional
information,
such
as
average
or
typical
rates,
were
available,
these
values
were
used
as
well
in
order
to
allow
risk
managers
to
make
a
more
informed
risk
management
decision.
Average
application
rates
were
available
from
the
SMART
meeting
and
BEAD's
QUA.
°
The
average
occupational
workday
is
assumed
to
be
8
hours.
The
daily
areas
to
be
treated
were
defined
for
each
handler
scenario
(in
appropriate
units)
by
determining
the
amount
that
can
be
reasonably
treated
in
a
single
day
(e.
g.
acres,
animals).
The
factors
used
for
the
carbaryl
assessment
are
the
same
as
those
detailed
in
the
HED
Science
Advisory
Committee
on
Exposure
Policy
9:
Standard
Values
for
Daily
Acres
Treated
in
Agriculture.
The
daily
volumes
handled
and
acres
treated,
excerpted
from
the
policy,
in
each
occupational
scenario
include:
10
The
veterinary
and
fireant
treatments
are
not
included
in
the
policy
but
represent
values
that
have
been
used
by
HED
in
previous
assessments.
84
°
Aerial
applications:
1200
acres
for
large
field
crops
and
forest
treatments,
350
acres
for
other
field
crops,
and
7500
acres
for
mosquito
control
adulticide
applications;
°
Groundboom:
200
acres
for
large
field
crops
(e.
g.,
wheat
and
corn),
80
acres
treated
for
other
field
crop
groundboom
applications,
and
40
acres
on
golf
course
turf;
°
Airblast:
40
acres
treated
for
agricultural
applications;
°
8
pet
animals
treated
per
day
for
veterinary
and
professional
groomer
uses
10
;
°
1000
gallons
of
spray
solution
prepared
when
mixing/
loading
liquids
for
high
pressure
handwand
application
or
making
the
application;
°
40
gallons
when
mixing/
loading/
applying
liquids
with
a
backpack
sprayer
or
a
low
pressure
handwand
sprayer;
°
10
mounds
per
day
treated
for
fire
ant
applications.
10
°
For
direct
pet
animal
treatments,
the
Residential
SOPs,
were
used
to
define
the
amount
of
chemical
that
can
be
used
to
treat
a
single
animal,
which
in
turn
was
used
to
calculate
total
human
dose
levels.
The
actual
per
animal
application
rates
used
were
½
of
a
6
oz
bottle
for
liquid
shampoos
(0.5%)
and
½
of
4
lb
container
for
animal
powders
(10%).
°
Ultra
low
volume
applications
for
uses,
such
as
adulticide
mosquito
control,
were
considered
using
a
large
acreage
estimate
to
aerial
applicators.
The
mosquito
adulticide
uses
were
evaluated
in
the
same
manner
as
other
chemicals
used
for
that
purpose
(e.
g.,
the
same
acreage
estimates
were
used
as
for
other
chemicals
like
fenthion
and
naled).
°
There
were
several
scenarios
which
were
identified
for
which
no
appropriate
exposure
data
are
known
to
exist.
These
include:
animal
grooming
dust
application;
dust
applications
in
agriculture;
handheld
fogging
for
mosquito
and
other
pest
treatments;
power
backpack
application;
tree
injection;
and
drenching/
dipping
seedlings
(the
mixing/
loading
component
only
of
this
scenario
has
been
addressed
quantitatively).
The
unit
exposure
values
(mg
ai
exposure/
lb
ai
handled)
used
in
this
assessment
were
predominantly
based
on
PHED
and
summarized
in
the
surrogate
exposure
guidance.
In
addition
to
PHED,
five
studies
were
used
by
the
Agency.
One
used
carbaryl
to
quantify
exposures
for
professional
dog
groomers.
Two
were
completed
by
Aventis
Crop
Science
using
other
chemicals
that
quantified
exposures
to
granular
products
using
a
backpack
application
device.
One
was
submitted
by
Bayer
(now
in
the
process
of
acquiring
Aventis
Crop
Science
and
with
a
signed
PHED
data
waiver)
that
quantified
exposures
using
a
ready
to
use
trigger
sprayer.
Lastly,
an
ORETF
(Outdoor
Residential
Exposure
Task
Force,
of
which
Aventis
Crop
Science
is
a
member)
study
that
quantified
exposures
of
professional
11
Non
ORETF
data
included
in
MRIDs
451672
01
and
452507
01
were
from
studies
submitted
by
Aventis
Crop
Science.
The
propoxur
trigger
sprayer
study
has
a
signed
PHED
data
waiver
but
has
not
been
included
into
PHED.
It
also
is
the
property
of
Bayer
Crop
Science
which
has
recently
acquired
Aventis
Crop
Science.
Some
of
the
handler
exposure
data
used
in
this
assessment
are
from
the
ORETF,
of
which
Aventis
Crop
Science,
is
a
member.
85
lawncare
operators
using
granular
and
liquid
products.
There
are
no
data
compensation
issues
with
any
of
these
data.
11
In
all
cases,
what
appears
to
be
the
best
available
data
have
been
used
to
complete
the
calculations.
7.1.1
Occupational
Handler
Non
Cancer
Risks
Noncancer
risks
were
calculated
using
the
MOE
approach,
as
described
under
4.4.2.1.
The
major
differences
are
that
personal
protective
devices
are
used
and
longer
duration
exposures
(i.
e.,
intermediate
term
and
chronic)
have
been
considered
as
appropriate.
Risk
estimates
for
short
and
intermediate
term
exposures
are
similar
because
all
numerical
inputs
for
both
durations
and
the
target
MOEs
were
identical.
A
NOAEL
from
the
21
day
dermal
toxicity
study
in
rats
using
technical
grade
carbaryl
was
used
to
calculate
results
for
both
durations
(i.
e.,
20
mg/
kg/
day).
A
NOAEL
from
the
developmental
neurotoxicity
study
in
rats,
that
also
observed
at
the
same
level
in
a
subchronic
neurotoxicity
study
in
rats
(i.
e.,
1
mg/
kg/
day),
was
used
to
calculate
inhalation
risks.
The
target
MOE
was
100
for
all
assessments.
In
the
chronic
assessments,
a
LOAEL
(3.1.
mg/
kg/
day)
has
been
used
from
a
1
year
dog
feeding
study
for
both
dermal
and
inhalation
exposures
(with
a
dermal
absorption
factor
of
12.7
percent
applied).
The
target
MOE
for
the
chronic
assessments
is
300
because
a
LOAEL
was
used
instead
of
a
NOAEL.
Short/
Intermediate
term
Risks:
In
most
scenarios,
MOEs
meet
or
exceed
the
required
uncertainty
factor
of
100
at
some
level
of
personal
protection.
For
the
most
part,
current
label
requirements
for
personal
protection
(single
layer
clothing,
gloves,
and
no
respirator)
appear
to
be
generally
inadequate
for
most
scenarios
except
for
operations
where
exposures
are
low
and
the
amount
of
chemical
used
is
also
low.
Table
21
summarizes
the
results
for
short
term
and
intermediate
term
occupational
handlers.
[Note:
Scenarios
where
MOEs
are
still
of
concern
(i.
e.,
<100)
for
any
personal
protection
considered
are
highlighted
and
just
the
minimum
required
personal
protective
equipment
(PPE)
is
highlighted
if
it
exceeds
current
label
requirements
but
target
MOEs
can
be
achieved
at
higher
than
label
requirements
for
mitigation.]
Table
21:
Summary
of
Short/
Intermediate
Term
Occupational
Handler
Noncancer
Risks
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
MOEs
Min.
Req.
PPE
Mixer/
Loaders
1a
Dry
Flowable:
Aerial/
Chemigation
1
2
(wheat/
corn)
2
5
(veg.,
stone
fruit,
24C
on
oysters)
1200
350
363
726
498
1244
EC
EC
1b
Dry
Flowable:
Airblast
7.5
16
(various
fruit
&
nut
trees)
5
(nuts)
1.1
3
(pome
&
stone
fruit,
grapes)
40
40
40
1360
2902
101
143
391
EC
SL/
GL/
PF5
Baseline
Table
21:
Summary
of
Short/
Intermediate
Term
Occupational
Handler
Noncancer
Risks
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
MOEs
Min.
Req.
PPE
86
1c
Dry
Flowable:
Groundboom
1.5
2
(wheat/
corn)
2
(strawberry/
veg)
8
(turf/
golf
courses)
4
(turf/
golf
courses)
200
80
40
40
2177
2902
107
2721
108
EC
Baseline
EC
Baseline
1d
Dry
Flowable:
High
Press
HW/
ROW
Sprayer
4
lb
ai/
100
gal
(poultry)
1000
gal
430
Baseline
1e
Dry
Flowable:
Low
press./
High
Vol.
Turfgun
4
8
(LCO
on
turf)
5
430
860
Baseline
1f
Dry
Flowable:
Wide
area
aerial
2
(rangeland/
forestry)
7500
58
MOE
<
100
2a
Granular:
Aerial
Application
2
(corn)
2
(corn)
1200
350
688
146
EC
SL/
GL/
PF5
2b
Granular:
Solid
broadcast
spreader
1.5
(wheat/
corn)
2
(wheat/
corn)
2
(vegetables)
6
(turf/
golf
courses)
9
(turf/
golf
courses)
200
200
80
40
40
110
256
206
138
284
Baseline
SL/
GL/
PF5
Baseline
Baseline
SL/
GL/
PF5
3a
Liquid:
Aerial/
Chemigation
1.5
2
(wheat,
max
corn)
1
(avg.
corn)
5
(stone
fruit)
2
(vegetables)
1200
1200
350
350
57
76
114
78
103
All
MOEs
<
100
EC
MOE<
100
DL/
GL/
PF10
3b
Liquid:
Airblast
Application
16
(Citrus
24C
in
California)
7.5
(Citrus)
5
(Nuts)
1.1
3
(Grapes,
pome
&
stone
fruit)
40
40
40
40
100
168
149
248
677
DL/
GL/
PF10
SL/
GL/
PF5
SL/
GL/
NR
SL/
GL/
NR
3c
Liquid:
Groundboom
1.5
(wheat)
2
(corn)
2
(strawberries)
8
(turf/
golf
courses)
4
(turf/
golf
courses)
200
200
80
40
40
168
126
186
157
186
SL/
GL/
PF5
SL/
GL/
PF5
SL/
GL/
NR
SL/
GL/
PF5
SL/
GL/
NR
3d
Liquid:
High
Press
HW/
ROW
Sprayer
4
lb
ai/
100
gal
(poultry)
1000
gal
745
SL/
GL/
NR
3e
Liquid:
Low
press./
High
Vol.
Turfgun
4
8
(LCO
on
turf)
5
745
1489
SL/
GL/
NR
3f
Liquid:
Wide
area
aerial
2
(Range/
Forestry)
0.016
(Mosquito
adulticide)
0.15
(Mosquito
adulticide)
1
(Mosquito
adulticide)
7500
7500
7500
7500
9
248
121
18
MOE
<
100
SL/
GL/
NR
EC
MOE
<
100
3g
Liquid:
Wide
area
ground
0.016
(Mosquito
adulticide)
0.15
(Mosquito
adulticide)
1
(Mosquito
adulticide)
3000
3000
3000
621
112
45
SL/
GL/
NR
SL/
GL/
PF5
MOE
<
100
4a
Wettable
Powders:
Aerial
1
2
(Wheat/
corn)
5
(stone
fruit)
2
(vegetables)
1200
350
350
40
80
55
137
All
MOEs
<
100
MOE
<
100
EC
4b
Wettable
Powders:
Airblast
16
(Citrus
24C
in
California)
1.1
7.5
(Citrus,
nuts,
grapes,
pome
&
stone
fruit)
40
40
150
320
2180
EC
EC
Table
21:
Summary
of
Short/
Intermediate
Term
Occupational
Handler
Noncancer
Risks
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
MOEs
Min.
Req.
PPE
87
4c
Wettable
Powders:
Groundboom
1.5
2
(wheat/
corn)
2
(strawberries)
4
8
(turf/
golf
courses)
200
80
40
240
320
599
299
599
EC
EC
EC
4d
Wettable
Powders:
High
Press
HW/
ROW
Sprayer
4
lb
ai/
100
gal
(poultry)
1000
gal
102
SL/
GL/
PF5
4e
Wettable
Powders:
Low
press./
High
Vol.
Turfgun
4
(LCO
on
turf)
8
(LCO
on
turf)
5
5
102
205
SL/
GL/
PF5
SL/
GL/
PF5
4f
Wettable
Powders:
Wide
area
aerial
2
(Range/
Forestry)
7500
6
MOE<
100
Applicators
5a
Aerial:
Agricultural
uses,
liquid
sprays
1
1.5
(wheat/
avg.
corn)
2
(max
corn)
5
(stone
fruit)
2
(vegetables,
24C
on
oysters)
1200
1200
350
350
113
170
85
116
292
EC
MOE<
100
EC
EC
5b
Aerial:
Wide
area
uses,
liquid
sprays
2
(Range/
Forestry)
0.016
0.15
(Mosquito
adulticide)
1
(Mosquito
adulticide)
7500
7500
7500
14
181
1700
27
MOE<
100
EC
MOE<
100
5c
Aerial:
Agricultural
uses,
granular
applications
2
(corn)
2
(corn)
1200
350
21
72
MOE<
100
MOE<
100
6a
Airblast:
Agricultural
uses
16
(Citrus
24C
in
California)
2
7.5
(Citrus,
nuts,
grapes,
pome
&
max.
stone
fruit)
1.1
(avg.
stone
fruit)
40
40
40
105
224
841
123
EC
EC
SL/
GL/
PF5
6b
Airblast:
Wide
area
uses,
liquid
sprays
0.016
(Mosquito
adulticide)
0.15
(Mosquito
adulticide)
1
(Mosquito
adulticide)
3000
3000
3000
113
150
22
SL/
GL/
PF5
EC
MOE<
100
7
Groundboom
1.5
2
(Wheat,
corn)
2
(Strawberries)
4
8
(Turf/
golf
course)
200
80
40
122
162
304
152
304
Baseline
Baseline
Baseline
8
Solid
broadcast
spreader
(granular)
1.
5
2
(Wheat,
corn)
2
(Strawberries)
4
8
(Turf/
golf
course)
200
80
40
103
138
258
115
172
Baseline
Baseline
Baseline
9
Aerosol
Can
0.
01
lb
ai/
can
2
cans
324
Baseline
10
Trigger
pump
sprayer
0.
01
lb
ai/
can
1
can
8772
SL/
GL/
NR
11
Right
of
way
sprayer
1.
5
lb
ai/
100
gallons
1000
gallons
199
SL/
GL/
NR
12
High
pressure
handwand
4
lb
ai/
100
gallons
1000
gallons
66
MOE<
100
13
Animal
groomer,
liquid
application
0.
01
lb
ai/
dog
8
dogs
9.7
MOE<
100
14
Animal
groomer,
dust
application
0.2
lb
ai/
dog
8
dogs
8750
Baseline
(dermal
exp
only)
15
Granulars
&
baits
applied
by
hand
9
(Ornamentals
&
gardens)
1
3.8
MOE<
100
16
Granulars
&
baits
applied
by
spoon
9
(Ornamentals
&
garderns)
1
75.1
MOE<
100
Table
21:
Summary
of
Short/
Intermediate
Term
Occupational
Handler
Noncancer
Risks
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
MOEs
Min.
Req.
PPE
88
Mixerr/
Loader/
Applicators
17
Low
pressure,
high
volume
turfgun
(ORETF
Data)
8
(LCO
Use
on
turf)
4
(LCO
Use
on
turf)
5
5
94
104
MOE<
100
SL/
GL/
PF5
18a
Wettable
powder,
low
pressure
handwand
1
lb
ai/
1000
ft
2
(poultry
house)
2%
solution
(ornamentals)
20,000
ft
2
40
gallons
8.3
135
MOE<
100
SL/
GL/
PF5
18b
Liquids,
low
pressure
handwand
1
lb
ai/
1000
ft
2
(poultry
house)
2%
solution
(ornamentals)
20,000
ft
2
40
gallons
127
1699
SL/
GL/
PF5
SL/
GL/
NR
19
Backpack
sprayer
1
lb
ai/
1000
ft
2
(poultry
house)
2%
solution
(ornamentals)
20,000
ft
2
40
gallons
42
565
MOE<
100
Baseline
20
Granular,
bellygrinder
9
(Turf)
1
27
MOE<
100
21
Granular,
push
type
spreader
9
(Turf)
5
124
SL/
GL/
PF5
22
Handheld
fogger
No
data
No
data
No
data
No
data
23
Power
backpack
No
data
No
data
No
data
No
data
24
Granular,
backpack
9
(Ornamentals)
1
1562
DL/
GL/
NR
25
Tree
injection
No
data
No
data
No
data
No
data
26
Drench/
dipping
forestry/
ornamentals
1.5
lb
ai/
100
gallons
(Ornamental/
seedling
dip)
100
gallons
199
SL/
GL/
NR
27
Sprinkler
can
2%
solution
(Ornamentals)
10
gallons
226
Baseline
Flaggers
28a
Flagger:
liquid
sprays
2
(Corn)
2
(Vegetables)
1200
350
249
111
EC
Baseline
28b
Flagger:
granular
applications
2
(Corn)
2
(Vegetables)
1200
350
101
345
Baseline
Baseline
Baseline
=
Long
pants,
long
sleeved
shirts,
no
gloves
SL
=
Single
layer
clothing
with
or
without
gloves
(GL
or
NG)
DL
=
Double
layer
clothing
(i.
e.,
coveralls
over
SL)
with
or
without
gloves
(GL
or
NG)
EC
=
Engineering
controls
NR
=
No
respirator
PF5
=
Protection
factor
5
respirator
PF10
=
Protection
factor
10
respirator
Current
label
=
SL/
GL/
NR
Min.
Req.
PPE
=
level
of
PPE
where
MOEs
>
100,
where
current
label
is
exceeded
or
no
adequate
PPE
is
found,
results
are
bold.
MOEs
which
never
exceed
100
are
for
highest
feasible
type
of
mitigation
(e.
g.,
engineering
control
in
most
cases).
89
Chronic
Risks:
MOEs
were
calculated
for
only
a
limited
number
of
exposure
ornamental
use
scenarios
where
the
Agency
believes
that
this
kind
of
exposure
pattern
may
exist.
These
calculations
were
also
completed
at
different
levels
of
personal
protection
as
illustrated
in
Table
22.
For
most
scenarios
(3
of
5),
MOEs
meet
or
exceed
the
required
uncertainty
factor
of
300
at
some
level
of
personal
protection.
The
granular
hand
application
scenarios
are
problematic.
The
uncertainty
factor
of
300
is
required
for
the
chronic
exposure
scenarios
because
a
LOAEL
and
not
a
NOAEL
was
used
for
risk
assessment.
Table
22:
Summary
of
Chronic
Occupational
Handler
Noncancer
Risks
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
MOEs
Min.
Req.
PPE
Applicators
15
Granulars
&
baits
applied
by
hand
9
(Ornamentals
&
gardens)
1
4.7
MOE<
300
16
Granulars
&
baits
applied
by
spoon
9
(Ornamentals
&
garderns)
1
92.6
MOE<
300
Mixer/
Loader/
Applicators
18a
Wettable
powder,
low
pressure
handwand
2%
solution
(ornamentals)
40
gallons
302
DL/
GL/
PF10
18b
Liquids,
low
pressure
handwand
2%
solution
(ornamentals)
40
gallons
3206
SL/
GL/
NR
19
Backpack
sprayer
2%
solution
(ornamentals)
40
gallons
781
Baseline
Baseline
=
Long
pants,
long
sleeved
shirts,
no
gloves
SL
=
Single
layer
clothing
with
or
without
gloves
(GL
or
NG)
DL
=
Double
layer
clothing
(i.
e.,
coveralls
over
SL)
with
or
without
gloves
(GL
or
NG)
EC
=
Engineering
controls
NR
=
No
respirator
PF5
=
Protection
factor
5
respirator
PF10
=
Protection
factor
10
respirator
Current
label
=
SL/
GL/
NR
Min.
Req.
PPE
=
level
of
PPE
where
MOEs
>
300,
where
current
label
is
exceeded
or
no
adequate
PPE
is
found,
results
are
bold.
MOEs
which
never
exceed
300
are
for
highest
feasible
type
of
mitigation
(e.
g.,
PPE
in
most
cases).
7.1.2
Occupational
Handler
Cancer
Risks
Cancer
risks
were
calculated
by
multiplying
the
LADD
to
the
Q1*
(8.75
x
10
4
(mg/
kg/
day)
1
),
as
described
in
4.4.2.2.
HED
considered
two
distinct
populations
in
the
cancer
risk
assessment
private
growers
at
10
use
events
per
year
and
commercial
applicators
with
a
use
pattern
of
30
days
per
year.
The
Agency
has
defined
a
range
of
acceptable
cancer
risks
based
on
a
policy
memorandum
dated
August
14,
1996,
by
Office
of
Pesticide
Programs
Director
Dan
Barolo.
This
memo
refers
to
a
predetermined
quantified
"level
of
concern"
for
occupational
carcinogenic
risk.
Risks
that
are
1
x
10
6
or
lower
require
no
risk
management
action.
For
those
chemicals
subject
to
reregistration,
the
Agency
is
to
carefully
examine
uses
with
estimated
risks
in
the
10
6
to
10
4
range
to
seek
ways
of
cost
effectively
reducing
risks.
If
carcinogenic
risks
are
in
this
range
for
occupational
handlers,
increased
levels
of
90
personal
protection
are
warranted
as
is
commonly
applied
with
noncancer
risk
estimates
(e.
g.,
additional
PPE
or
engineering
controls).
Carcinogenic
risks
that
remain
above
1
x
10
4
at
the
highest
level
of
mitigation
appropriate
for
that
scenario
remain
a
concern.
Cancer
risks
for
private
growers
(i.
e.,
10
applications
per
year)
were
calculated
for
different
exposure
scenarios
at
different
levels
of
personal
protection.
All
scenarios
for
private
growers
have
risks
that
are
<1x10
4
at
some
level
of
personal
protection
specified
in
the
Barolo
memo.
In
fact,
for
all
but
one
scenario
(Scen
4f:
Mixing/
loading
Wettable
Powders
for
wide
area
aerial
applications)
cancer
risks
are
<1x10
4
at
current
label
requirements
for
personal
protection.
If
a
1x10
6
risk
level
is
specified
as
a
concern,
results
are
similar
in
that
risks
for
a
majority
of
scenarios
are
<1x10
6
at
current
label
requirements.
In
fact,
only
8
of
the
128
scenarios
considered
for
private
growers
have
cancer
risks
>1x10
6
(and
less
than
1x10
4
)
even
when
the
most
protective
ensembles
of
either
protective
clothing
or
engineering
controls
are
considered.
As
with
the
risks
calculated
for
private
growers,
cancer
risks
for
commercial
applicators
(i.
e.,
30
applications
per
year)
were
calculated
for
different
exposure
scenarios
at
different
levels
of
personal
protection.
Again,
risks
for
all
but
one
scenario
(Scen
4f:
Mixing/
loading
Wettable
Powders
for
wide
area
aerial
applications)
are
less
than
the
1x10
4
level
specified
in
the
Barolo
memo
at
current
label
requirements
for
personal
protection
(i.
e.,
risks
for
this
scenario
are
<
1x10
4
if
additional
protective
clothing
or
equipment
is
used).
If
a
1x10
6
risk
level
is
specified
as
a
concern
for
commercial
applicators,
results
indicate
that
risks
for
about
half
of
the
scenarios
considered
are
<1x10
6
at
current
label
requirements
and
that
only
21
of
the
128
scenarios
considered
have
cancer
risks
>1x10
6
(and
less
than
1x10
4
)
even
when
the
most
protective
ensembles
of
either
protective
clothing
or
engineering
controls
are
considered.
In
general,
the
cancer
risk
estimates
would
lead
to
less
restrictive
measures
when
compared
to
the
noncancer
results.
Table
23
below
provides
a
summary
of
the
cancer
risks
that
have
been
calculated
for
private
growers
and
commercial
applicators.
Table
23:
Summary
of
Occupational
Handler
Cancer
Risks
For
Private
Growers
and
Commercial
Applicators
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
Private
Growers
Commercial
Applicators
Risk
Min.
Req.
PPE
Risk
Min.
Req.
PPE
Mixer/
Loaders
1a
Dry
Flowable:
Aerial/
Chemigation
1
2
(wheat/
corn)
5
(stone
fruit)
2
(vegetables,
24C
on
oysters)
1200
350
350
3.7
to
7.4x10
8
5.4x10
8
1.0x10
6
EC
EC
SL/
GL/
PF10
1.1
to
2.2x10
7
1.6x10
7
6.5x10
8
EC
EC
EC
1b
Dry
Flowable:
Airblast
16
(Citrus,
24C
in
CA)
1.1
7.5
(grapes,
various
fruit
&
nut
trees)
40
40
1.0x10
6
6.9x10
8
to
4.7x10
7
Baseline
Baseline
5.9x10
8
1.4
to
9.3x10
7
EC
DL/
GL/
PF10
1c
Dry
Flowable:
Groundboom
2
(corn)
1.5
(wheat)
2
(strawberry/
veg)
8
(turf/
golf
courses)
4
(turf/
golf
courses)
200
200
80
40
40
4.7x10
7
6.3x10
7
2.5x10
7
5.0x10
7
2.5x10
7
Baseline
Baseline
Baseline
Baseline
Baseline
1.0x10
6
3.7x10
8
7.5x10
7
1.0x10
6
7.5x10
7
DL/
GL/
NR
EC
Baseline
DL/
GL/
PF5
Baseline
1d
Dry
Flowable:
High
Press
HW/
ROW
Sprayer
4
lb
ai/
100
gal
(poultry)
1000
gal
6.3x10
8
Baseline
1.9x10
7
Baseline
1e
Dry
Flowable:
Low
press./
High
Vol.
Turfgun
4
8
(LCO
on
turf)
5
3.1
to
6.3x10
8
Baseline
9.4x10
8
to
1.9x10
7
Baseline
1f
Dry
Flowable:
Wide
area
aerial
2
(rangeland/
forestry)
7500
4.6x10
7
EC
1.4x10
6
All
<
1x10
6
Table
23:
Summary
of
Occupational
Handler
Cancer
Risks
For
Private
Growers
and
Commercial
Applicators
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
Private
Growers
Commercial
Applicators
Risk
Min.
Req.
PPE
Risk
Min.
Req.
PPE
91
2a
Granular:
Aerial
Application
2
(corn)
2
(corn)
1200
350
5.0x10
7
3.3x10
7
SL/
GL/
PF5
Baseline
9.5x10
7
9.9x10
7
DL/
GL/
PF5
Baseline
2b
Granular:
Solid
broadcast
spreader
1.5
2
(wheat/
corn)
2
(vegetables)
6
9
(turf/
golf
courses)
200
80
40
1.4
to
1.9x10
7
7.6x10
8
1.1
to
1.7x10
7
Baseline
Baseline
Baseline
4.3
to
5.7x10
7
2.3x10
7
3.4
to
5.1x10
7
Baseline
Baseline
Baseline
3a
Liquid:
Aerial/
Chemigation
1
(avg.
corn)
1.5
(wheat)
2
(corn)
5
(stone
fruit)
2
(vegetables)
1200
1200
1200
350
350
9.7x10
7
9.9x10
7
8.5x10
7
9.5x10
7
4.9x10
7
SL/
GL/
PF5
DL/
GL/
PF5
SL/
GL/
NR
SL/
GL/
PF5
SL/
GL/
NR
1.1x10
6
1.4x10
6
7.2x10
7
1.1x10
6
8.6x10
7
All
<
1x10
6
All
<
1x10
6
EC
All
<
1x10
6
DL/
GL/
PF5
3b
Liquid:
Airblast
Application
16
(citrus,
24C
in
CA)
1.1
7.5
(grapes,
various
fruit
&
nut
trees)
40
40
4.5x10
7
3.1x10
8
to
2.1x10
7
SL/
GL/
NR
SL/
GL/
NR
1.0x10
6
9.3x10
8
to
6.4x10
7
SL/
GL/
PF5
SL/
GL/
NR
3c
Liquid:
Groundboom
1.5
2
(wheat/
corn)
2
(strawberries)
4
8
(turf/
golf
courses)
200
80
40
2.1
to
2.8x10
7
1.1x10
7
1.1
to
2.3x10
7
SL/
GL/
NR
SL/
GL/
NR
SL/
GL/
NR
6.4
to
8.5x10
7
3.4x10
7
3.4
to
6.8x10
7
SL/
GL/
NR
SL/
GL/
NR
SL/
GL/
NR
3d
Liquid:
High
Press
HW/
ROW
Sprayer
4
lb
ai/
100
gal
(poultry)
1000
gal
2.8x10
8
SL/
GL/
NR
8.5x10
8
SL/
GL/
NR
3e
Liquid:
Low
press./
High
Vol.
Turfgun
4
8
(LCO
on
turf)
5
1.4
to
2.8x10
8
SL/
GL/
NR
4.2
to
8.5x10
8
SL/
GL/
NR
3f
Liquid:
Wide
area
aerial
2
(Range/
Forestry)
0.016
(Mosquito
adulticide)
0.15
(Mosquito
adulticide)
1
(Mosquito
adulticide)
7500
7500
7500
7500
3.0x10
6
8.5x10
8
7.9x10
7
1.5x10
6
All
<
1x10
6
SL/
GL/
NR
SL/
GL/
NR
All
<
1x10
6
9.1x10
6
2.5x10
7
6.8x10
7
4.5x10
6
All
<
1x10
6
SL/
GL/
NR
EC
All
<
1x10
6
3g
Liquid:
Wide
area
ground
0.016
(Mosquito
Adulticide)
0.15
(Mosquito
adulticide)
1
(Mosquito
adulticide)
3000
3000
3000
3.4x10
8
3.2x10
7
6.0x10
7
SL/
GL/
NR
SL/
GL/
NR
EC
1.0x10
7
9.5x10
7
1.8x10
6
SL/
GL/
NR
SL/
GL/
NR
All
<
1x10
6
4a
Wettable
Powders:
Aerial
1.5
(Wheat)
2
(Corn
max)
1
(Corn
typ)
5
(stone
fruit)
2
(vegetables)
1200
1200
1200
350
350
4.6x10
7
6.1x10
7
3.1x10
7
4.4x10
7
1.8x10
7
EC
EC
EC
EC
EC
1.4x10
6
1.8x10
6
9.2x10
7
1.3x10
6
5.3x10
7
All
<
1x10
6
All
<
1x10
6
EC
All
<
1x10
6
EC
4b
Wettable
Powders:
Airblast
16
(Citrus
24C
in
California)
7.5
(Citrus)
5
(Nuts)
3
(Pome
&
stone
fruit)
2
(Grapes)
1.1(
Avg.
stone
fruit)
40
40
40
40
40
40
1.6x10
7
7.6x10
8
1.0x10
6
6.2x10
7
8.8x10
7
4.9x10
7
EC
EC
SL/
GL/
PF5
SL/
GL/
PF5
SL/
GL/
NR
SL/
GL/
NR
4.9x10
7
2.3x10
7
1.5x10
7
9.2x10
8
1.0x10
6
5.7x10
7
EC
EC
EC
EC
DL/
GL/
PF5
DL/
GL/
PF5
4c
Wettable
Powders:
Groundboom
1.5
(wheat)
2
(corn)
2
(strawberries)
8
(turf/
golf
courses)
4
(turf/
golf
courses)
200
200
80
40
40
7.6x10
8
1.0x10
7
8.3x10
7
8.1x10
8
8.3x10
7
EC
EC
SL/
GL/
PF5
EC
SL/
GL/
PF5
2.3x10
7
3.1x10
7
1.2x10
7
2.4x10
7
1.2x10
7
EC
EC
EC
EC
EC
4d
Wettable
Powders:
High
Press
HW/
ROW
Sprayer
4
lb
ai/
100
gal
(poultry)
1000
gal
4.4x10
7
SL/
GL/
NR
5.2x10
7
DL/
GL/
PF5
4e
Wettable
Powders:
Low
press./
High
Vol.
Turfgun
4
(LCO
on
turf)
8
(LCO
on
turf)
5
5
2.2x10
7
4.4x10
7
SL/
GL/
NR
SL/
GL/
NR
6.6x10
7
6.2x10
7
SL/
GL/
NR
SL/
GL/
PF5
4f
Wettable
Powders:
Wide
area
aerial
2
(Range/
Forestry)
7500
3.8x10
6
All
<
1x10
6
1.1x10
5
All
<
1x10
6
Table
23:
Summary
of
Occupational
Handler
Cancer
Risks
For
Private
Growers
and
Commercial
Applicators
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
Private
Growers
Commercial
Applicators
Risk
Min.
Req.
PPE
Risk
Min.
Req.
PPE
92
Applicators
5a
Aerial:
Agricultural
uses,
liquid
sprays
1
2
(wheat/
corn)
5
(stone
fruit)
2
(vegetables,
24C
on
oysters)
1200
350
350
1.6
to
3.2x10
7
2.3x10
7
9.2x10
8
EC
EC
EC
4.7
to
9.5x10
7
6.9x10
7
2.8x10
7
EC
EC
EC
5b
Aerial:
Wide
area
uses,
liquid
sprays
2
(Range/
Forestry)
0.016
(Mosquito
adulticide)
0.15
(Mosquito
adulticide)
1
(Mosquito
adulticide)
7500
7500
7500
7500
2.0x10
6
1.6x10
8
1.5x10
7
9.8x10
7
All
<
1x10
6
EC
EC
EC
5.9x10
6
4.7x10
8
4.4x10
7
3.0x10
6
All
<
1x10
6
EC
EC
All
<
1x10
6
5c
Aerial:
Agricultural
uses,
granular
applications
2
(corn)
2
(corn)
1200
350
6.2x10
7
1.8x10
7
EC
EC
1.9x10
6
5.5x10
7
All
<
1x10
6
EC
6a
Airblast:
Agricultural
uses
16
(Citrus
24C
in
California)
7.5
(Citrus)
5
(Nuts)
3
(Pome
&
stone
fruit)
2
(Grapes)
1.1
(Avg
pome
&
stone
fruit)
40
40
40
40
40
40
2.7x10
7
1.3x10
7
9.9x10
7
1.0x10
6
6.9x10
7
3.8x10
7
EC
EC
DL/
GL/
PF5
Baseline
Baseline
Baseline
8.2x10
7
3.9x10
7
2.6x10
7
1.5x10
7
1.0x10
7
7.9x10
7
EC
EC
EC
EC
EC
SL/
GL/
NR
6b
Airblast:
Wide
area
fogger
0.016
(Mosquito
adulticide)
0.15
(Mosquito
adulticide)
1
(Mosquito
adulticide)
3000
3000
3000
4.1x10
7
1.9x10
7
1.3x10
6
Baseline
EC
All
<
1x10
6
8.6x10
7
5.8x10
7
3.9x10
6
SL/
GL/
NR
EC
All
<
1x10
6
7
Groundboom
1.5
2
(Wheat/
corn)
2
(Strawberries)
8
(Turf/
golf
course)
4
(Turf/
golf
course)
200
80
40
40
1.3
to
1.7x10
7
6.9x10
8
1.4x10
7
6.9x10
8
Baseline
Baseline
Baseline
Baseline
3.9
to
5.2x10
7
2.1x10
7
4.1x10
7
2.1x10
7
Baseline
Baseline
Baseline
Baseline
8
Solid
broadcast
spreader
(granular)
1.5
2
(Wheat/
corn)
2
(Strawberries)
4
8
(Turf/
golf
course)
200
80
40
1.3
to
1.7x10
7
6.7x10
8
1.0
to
1.5x10
7
Baseline
Baseline
Baseline
3.8
to
5.0x10
7
2.0x10
7
3.0
to
4.5x10
7
Baseline
Baseline
Baseline
9
Aerosol
Can
0.01
lb
ai/
can
2
cans
8.7x10
8
Baseline
2.6x10
7
Baseline
10
Trigger
pump
sprayer
0.01
lb
ai/
can
1
can
3.1x10
9
SL/
GL/
NR
9.4x10
9
SL/
GL/
NR
11
Right
of
way
sprayer
1.5
lb
ai/
100
gallons
1000
gallons
4.3x10
7
Baseline
4.1x10
7
SL/
GL/
NR
12
High
pressure
handwand
4
lb
ai/
100
gallons
1000
gallons
6.6x10
7
SL/
GL/
PF5
1.1x10
6
All
<
1x10
6
13
Animal
groomer,
liquid
application
0.01
lb
ai/
dog
8
dogs
3.1x10
6
All
<
1x10
6
9.4x10
6
All
<
1x10
6
14
Animal
groomer,
dust
application
0.2
lb
ai/
dog
8
dogs
3.5x10
9
Baseline
1.0x10
8
Baseline
15
Granulars
&
baits
applied
by
hand
9
(Ornamentals
&
gardens)
1
8.0x10
6
All
<
1x10
6
2.4x10
5
All
<
1x10
6
16
Granulars
&
baits
applied
by
spoon
9
(Ornamentals
&
garderns)
1
4.6x10
7
SL/
GL/
NR
1.2x10
6
All
<
1x10
6
Mixerr/
Loader/
Applicators
17
Low
pressure,
high
volume
turfgun
(ORETF
Data)
8
(LCO
Use
on
turf)
4
(LCO
Use
on
turf)
5
5
3.1x10
7
6.1x10
7
SL/
GL/
NR
SL/
GL/
NR
9.7x10
7
9.2x10
7
DL/
GL/
PF5
SL/
GL/
NR
18a
Wettable
powder,
low
pressure
handwand
1
lb
ai/
1000
ft
2
(poultry
house)
2%
solution
(ornamentals)
20,000
ft
2
40
gallons
3.1x10
6
3.0x10
7
All
<
1x10
6
SL/
GL/
NR
9.2x10
6
9.0x10
7
All
<
1x10
6
SL/
GL/
NR
Table
23:
Summary
of
Occupational
Handler
Cancer
Risks
For
Private
Growers
and
Commercial
Applicators
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
Private
Growers
Commercial
Applicators
Risk
Min.
Req.
PPE
Risk
Min.
Req.
PPE
93
18b
Liquids,
low
pressure
handwand
1
lb
ai/
1000
ft
2
(poultry
house)
2%
solution
(ornamentals)
20,000
ft
2
40
gallons
2.1x10
7
1.2x10
8
SL/
GL/
PF5
SL/
GL/
NR
6.2x10
7
3.5x10
8
SL/
GL/
PF5
SL/
GL/
NR
19
Backpack
sprayer
1
lb
ai/
1000
ft
2
(poultry
house)
2%
solution
(ornamentals)
20,000
ft
2
40
gallons
7.0x10
7
4.8x10
8
DL/
GL/
PF5
Baseline
2.2x10
6
1.4x10
7
All
<
1x10
6
Baseline
20
Granular,
bellygrinder
9
(Turf)
1
1.1x10
6
All
<
1x10
6
3.4x10
6
All
<
1x10
6
21
Granular,
push
type
spreader
9
(Turf)
5
4.0x10
7
Baseline
8.2x10
7
SL/
GL/
NR
22
Handheld
fogger
No
data
No
data
No
data
No
data
No
data
No
data
23
Power
backpack
No
data
No
data
No
data
No
data
No
data
No
data
24
Granular,
backpack
9
(Ornamentals)
1
1.9x10
8
DL/
GL/
NR
5.8x10
8
DL/
GL/
NR
25
Tree
injection
No
data
No
data
No
data
No
data
No
data
No
data
26
Drench/
dipping
forestry/
ornamentals
1.5
lb
ai/
100
gallons
(Ornamental/
seedling
dip)
100
gallons
1.1x10
7
SL/
GL/
NR
3.2x10
7
SL/
GL/
NR
27
Sprinkler
can
2%
solution
(Ornamentals)
10
gallons
1.3x10
7
Baseline
4.0x10
7
Baseline
Flaggers
28a
Flagger:
liquid
sprays
2
(Corn)
2
(Vegetables)
1200
350
7.2x10
7
2.1x10
7
Baseline
Baseline
3.5x10
7
6.3x10
7
EC
Baseline
28b
Flagger:
granular
applications
2
(Corn)
2
(Vegetables)
1200
350
2.1x10
7
6.1x10
8
Baseline
Baseline
6.2x10
7
1.8x10
7
Baseline
Baseline
Baseline
=
Long
pants,
long
sleeved
shirts,
no
gloves
SL
=
Single
layer
clothing
with
or
without
gloves
(GL
or
NG)
DL
=
Double
layer
clothing
(i.
e.,
coveralls
over
SL)
with
or
without
gloves
(GL
or
NG)
EC
=
Engineering
controls
NR
=
No
respirator
PF5
=
Protection
factor
5
respirator
PF10
=
Protection
factor
10
respirator
Current
label
=
SL/
GL/
NR
Min.
Req.
PPE
=
level
of
PPE
where
cancer
risks
>
1x10
6
,
where
current
label
is
exceeded
or
no
adequate
PPE
is
found,
results
are
bold.
Risks
which
never
exceed
1x10
6
are
for
highest
feasible
type
of
mitigation
(e.
g.,
engineering
control
in
most
cases).
7.2
Postapplication
Exposures
and
Risks
Workers
can
be
exposed
to
carbaryl
residues
by
entering
previously
treated
areas
to
perform
activities.
Exposure
varies
with
the
specific
tasks
(i.
e.,
transfer
coefficient),
the
level
of
carbaryl
residue
in
the
environment
(i.
e.,
DFR
or
TTR
depending
upon
crop),
and
the
duration
of
the
activity.
Calculations
were
completed
using
the
same
approaches
as
already
outlined
above
for
the
residential
postapplication
risk
assessments
(Section
4.4.3:
Residential
Postapplication
Risks).
An
administrative
approach,
the
Restricted
Entry
Interval
(REI),
is
used
by
the
Agency
to
manage
risks
for
postapplication
workers
doing
hand
labor
activities
that
require
direct
contact
with
treated
plants.
The
REI
is
the
amount
of
time
required
between
application
of
a
pesticide
and
engaging
in
a
task
or
activity
in
a
treated
field
that
it
takes
for
residues
to
dissipate
to
an
appropriate
level.
Current
labels
for
carbaryl
specify
REIs
of
12
hours
after
application
for
all
crop/
cultural
practice
combinations.
In
other
cases
(e.
g.,
use
of
a
combine
or
other
mechanical
harvesting)
such
as
those
94
specified
in
the
Agency's
Worker
Protection
Standard
(40CFR170)
where
no
contact
will
occur,
the
Agency
does
not
rely
on
the
REI
approach
but
adheres
to
the
guidance
included
in
§170.110.(
c)(
3)
that
allows
for
entry
if
the
criteria
are
met.
The
Agency
also
considers
short
term
excursions
for
people
for
such
activities
as
unclogging
machinery
as
stipulated
in
the
guidance
included
in
§170.112.(
c).
The
Agency
encourages
the
use
of
viable
engineering
controls
and
other
means
to
reduce
exposures
provided
they
are
not
overly
burdensome
for
actual
workers.
Generally,
it
should
also
be
noted
that
the
use
of
personal
protective
equipment
or
other
types
of
equipment
to
reduce
exposures
for
postapplication
workers
is
not
considered
a
viable
alternative
for
the
regulatory
process
except
in
specialized
situations
(e.
g.,
a
rice
scout
will
wear
rubber
boots
in
flooded
paddies).
As
with
the
occupational
handlers,
a
scenario
driven
approach
is
used
to
assess
risks
for
reentry
workers.
The
Agency's
Policy
003.1
Science
Advisory
Council
For
Exposure
Policy
Regarding
Agricultural
Transfer
Coefficients
is
used
to
define
the
scenarios.
This
policy
presents
various
transfer
coefficients
which
represent
the
range
of
activities
associated
with
18
distinct
crop/
agronomic
groupings
based
on
different
types
of
job
tasks
or
activities
needed
to
produce
fruits,
vegetables,
grains,
and
other
crops.
In
this
scheme,
carbaryl
uses
were
identified
in
all
of
the
crop
groupings
included
in
the
policy.
As
such,
all
agronomic
crop
group/
transfer
coefficients
included
in
this
policy
were
used
to
calculate
postapplication
risks
for
carbaryl.
°
Low
Berry
(e.
g.,
lowbush
blueberries,
cranberries,
strawberries);
°
Bunch/
bundle
(e.
g.,
bananas,
hops,
tobacco);
°
Field/
row
crops,
low/
medium
(e.
g.,
alfalfa,
barley,
beans,
cotton,
peanuts,
peas);
°
Field/
row
crops,
tall
(e.
g.,
corn,
sorghum,
sunflowers);
°
Cut
flowers
(e.
g.,
floriculture
crops);
°
Sugarcane;
°
Trees/
fruit,
deciduous
(e.
g.,
apples,
apricots,
cherry,
peaches,
pears);
°
Trees/
fruit,
evergreen
(e.
g.,
avocados,
Christmas
trees,
citrus);
°
Trees/
nut
(e.
g.,
almonds,
hazelnuts,
macadamia,
pecans,
walnuts);
°
Turf/
sod
(e.
g.,
golf
courses,
sod
farms);
°
Vegetable/
root
(e.
g.,
beets,
carrots,
onions,
potatoes,
turnips);
°
Vegetable/
cucurbit
(e.
g.,
cantelope,
cucumber,
squash,
watermelon);
°
Vegetable/
fruiting
(e.
g.,
eggplant,
pepper,
tomato,
okra);
°
Vegetable/
head
and
stem
brassica
(e.
g.,
broccoli,
cauliflower,
brussel
sprouts,
cauliflower);
°
Vegetables/
leafy
(e.
g.,
collards,
greens,
lettuce,
parsley,
spinach,
napa);
°
Vegetables/
stem
and
stalk
(e.
g.,
artichoke,
asparagus,
pineapple);
°
Vine/
trellis
(e.
g.,
blackberries,
blueberries,
grapes,
kiwi,
raspberries);
and
°
Nursery
crops
(e.
g.,
container
and
B&
B
ornamentals).
[Note:
This
assessment
includes
the
latest
transfer
coefficients
for
nursery
crops
which
have
been
recently
submitted
by
ARTF
and
reviewed
by
the
Agency.
Additionally,
the
transfer
coefficient
for
fruit
tree
hand
thinning
has
been
reduced
from
original
policy
estimates
based
on
a
reinterpretation
by
the
Agency
of
the
dataset
upon
which
it
was
based.]
95
Data
and
Assumptions
A
series
of
assumptions
and
exposure
factors
served
as
the
basis
for
completing
the
occupational
postapplication
risk
assessments,
as
described
below.
The
assumptions
and
factors
used
in
the
risk
calculations
are
consistent
with
current
Agency
policy
for
completing
occupational
exposure
assessments
(e.
g.,
Exposac
Policy
3
and
guidelines
for
handling
DFR
data).
The
assumptions
and
factors
used
in
the
risk
calculations
include:
C
Many
assumptions
and
factors
which
are
common
to
both
handler
and
postapplication
risk
assessments
are
detailed
in
Section
7.1:
Occupational
Handler
Risk
Assessment
(e.
g.,
body
weight).
One
major
difference
is
that
in
the
handler
assessment,
many
different
combinations
of
application
rates
and
crop
acres
treated
were
considered
but
in
the
postapplication
assessment,
generally
only
maximum
application
rates
were
considered.
C
Four
dislodgeable
foliar
residue
(DFR)
studies
were
submitted
that
meet
current
Agency
guidelines
for
sampling
techniques
and
data
quality.
These
studies
were
conducted
with
carbaryl
by
the
Agricultural
Re
entry
Task
Force
(ARTF)
using
Iwata's
DFR
sampling
method
on
tobacco
(harvesting),
olives
(pruning),
sunflowers
(scouting),
and
cabbage
(weeding).
[Note:
Aventis
Crop
Science
is
a
member
of
the
ARTF
so
there
are
no
data
compensation
issues
associated
with
the
use
of
these
data.]
The
percent
of
transferability
averaged
approximately
16
percent
of
the
application
rate
for
the
crops.
A
turf
transferrable
residue
(TTR)
study
was
also
completed
by
Aventis
Crop
Science
using
the
ORETF
roller
method.
The
percent
of
transferability
averaged
approximately
1.1
percent
for
turf
measurements
at
three
different
sites.
HED
used
the
values
from
these
five
studies
for
all
postapplication
crops
and
scenarios
as
the
transferability
is
in
the
appropriate
range
for
use
in
risk
assessments.
C
Short
term
noncancer
risks
were
calculated
by
comparing
single
day
exposures
based
on
the
dissipation
of
carbaryl
residues
(i.
e.,
single
day
risks
were
calculated
based
on
daily
DFR
dissipation
values
over
time).
With
the
intermediate
term
postapplication
risk
calculations,
30
day
averages
based
on
DFR
dissipation
and
an
appropriate
duration
for
the
endpoint
were
used
to
calculate
postapplication
risks.
In
the
long
term
assessment,
a
30
day
average
was
used
based
on
the
likelihood
that
carbaryl
could
be
sprayed
at
least
once
a
month
in
the
ornamental
industry.
The
endpoints
used
are
the
same
as
those
described
above
for
the
dermal
component
in
the
handler
assessments
(i.
e.,
NOAEL
of
20
mg/
kg/
day
from
21
day
dermal
rat
toxicity
study
using
technical
material
target
MOE
=
100
and
LOAEL
of
3.1
mg/
kg/
day
from
a
chronic
dog
feeding
study
with
a
dermal
absorption
factor
defined
in
rats
target
MOE
=
300).
C
A
standard
pseudo
first
order
kinetics
analysis
was
used
to
analyze
carbaryl
residue
dissipation
over
time
as
outlined
in
the
Agency's
draft
Series
875
Postapplication
Exposure
Monitoring
Guidelines.
A
more
sophisticated
curve
fitting
approach
was
not
warranted
because
the
correlation
coefficients
in
the
analysis
were
appropriate
and
the
data
have
been
used
generically
to
extrapolate
to
a
variety
of
other
crops
where
decay
rates
and
mechanisms
may
differ.
C
When
the
available
DFR
data
were
extrapolated
to
other
crops,
the
data
were
adjusted
for
differences
in
application
rate
using
a
simple
proportional
approach.
Carbaryl
specific
residue
dissipation
data
were
extrapolated
to
crops
where
no
data
were
available.
The
tobacco
DFR
data
were
used
to
complete
all
assessments
for
the
crop/
activity
combinations
included
in
the
bunch/
bundle,
sugarcane,
and
vine/
trellis
agronomic
crop
groups.
The
olive
DFR
data
were
used
to
complete
all
assessments
for
the
crop/
activity
combinations
included
in
all
of
the
tree
fruit
and
96
nut
crop
groups.
The
sunflower
DFR
data
were
used
to
complete
all
assessments
for
the
crop/
activity
combinations
in
the
tall
field/
row
crop
group.
No
extrapolation
was
required
in
this
assessment.
The
cabbage
study
was
based
on
groundboom
application,
which
is
thought
to
be
much
more
prevalent
in
the
overall
use
pattern
for
carbaryl.
The
cabbage
DFR
data
were
used
to
complete
all
assessments
for
the
crop/
activity
combinations
included
in
the
berry,
cut
flower,
low/
medium
field
and
row,
and
all
vegetable
(i.
e.,
stem/
stalk,
brassica,
leafy,
fruiting,
cucurbits,
root)
agronomic
crop
groups.
The
turf
TTR
data
were
used
to
complete
all
assessments
for
the
crop/
activity
combinations
for
the
turf
agronomic
crop
group.
No
extrapolation
was
required
in
this
assessment.
°
There
were
several
scenarios
for
which
no
appropriate
exposure
data
are
known
to
exist.
There
are
many
kinds
of
potential
exposure
pathways
that
do
not
involve
foliar
contact
that
have
not
been
addressed
in
this
risk
assessment.
The
scenarios
include:
transplanting
many
crops
including
in
the
ornamental
and
forestry
industry;
thinning
some
crops
such
as
hops;
some
partially
mechanized
operations
that
also
involve
human
contact
(e.
g.,
cotton
harvesting
where
module
builders
and
trampers
are
used);
various
operations
with
Christmas
trees
such
as
pruning
or
baling;
and
various
operations
with
nut
production
such
as
sweeping
for
harvest.
°
Aventis
Crop
Science
is
in
the
process
of
conducting
a
biomonitoring
study
with
postapplication
workers
on
key
crops
of
concern
(i.
e.,
apples
and
cherries).
The
activities
that
were
monitored
included
hand
thinning
of
apples
and
hand
harvest
of
both
apples
and
cherries.
Based
on
discussions
with
Aventis
Crop
Science,
the
preliminary
results
indicate
that
levels
are
similar
to
those
predicted
in
the
Agency's
occupational
postapplication
risk
assessment.
7.2.1
Occupational
Postapplication
Noncancer
Risks
Current
label
requirements
specify
12
hour
REIs.
For
all
but
the
lowest
exposure
scenarios
in
some
crops,
short
term
MOEs
are
of
concern
(i.
e.,
less
than
the
required
uncertainty
factor
of
100)
at
the
current
REI.
Generally,
short
term
MOEs
meet
or
exceed
the
Agency
uncertainty
factor
in
the
range
of
3
to
5
days
for
lower
to
medium
exposure
activities
and
from
8
to
12
days
after
application
in
most
higher
exposure
scenarios.
Intermediate
term
MOEs
are
not
of
concern
generally
for
low
to
medium
level
exposures
but
are
of
concern
for
higher
level
exposures
such
as
harvesting
in
some
crops.
Chronic
exposures
are
of
concern
for
the
cut
flower
industry
but
not
for
general
greenhouse
and
nursery
production
activities.
Table
24
below
provides
a
summary
of
the
noncancer
risks
that
have
been
calculated
for
each
crop
group
and
each
duration
of
exposure.
The
information
presented
includes
the
short
term
MOEs
on
the
day
of
application,
the
day
after
application
where
the
short
term
MOEs
meet
or
exceed
the
target
of
100,
the
intermediate
term
MOEs
based
on
30
day
average
exposures,
and
chronic
MOEs
also
based
on
30
day
average
exposures
(only
for
a
limited
number
of
scenarios).
Table
24:
Summary
of
Carbaryl
Noncancer
Postapplication
Worker
Risks
Crop
Group
Result
Type
Exposure
Descriptor
Very
Low
Low
Medium
High
Very
High
Low
Berry
ST
MOE
Day
0
NA
184
NA
49
NA
Days
For
ST
MOE
>
UF
NA
0
NA
4
NA
Table
24:
Summary
of
Carbaryl
Noncancer
Postapplication
Worker
Risks
Crop
Group
Result
Type
Exposure
Descriptor
Very
Low
Low
Medium
High
Very
High
97
IT
30
Day
Avg
MOE
NA
991
NA
264
NA
Bunch/
Bundle
ST
MOE
Day
0
NA
411
32
21
NA
Days
For
ST
MOE
>
UF
NA
0
6
8
NA
IT
30
Day
Avg
MOE
NA
2365
182
118
NA
Low
/Med.
Field/
Row
Crops
ST
MOE
Day
0
NA
982
65
39
NA
Days
For
ST
MOE
>
UF
NA
0
3
5
NA
IT
30
Day
Avg
MOE
NA
5286
352
211
NA
Tall
Field/
Row
Crops
ST
MOE
Day
0
NA
245
61
25
<1
Days
For
ST
MOE
>
UF
NA
0
4
11
+30
IT
30
Day
Avg
MOE
NA
970
242
97
6
Cut
Flowers
ST
MOE
Day
0
NA
30
18
11
NA
Days
For
ST
MOE
>
UF
NA
7
9
12
NA
IT
30
Day
Avg
MOE
NA
159
99
57
NA
Chronic
MOE
NA
194
121
69
NA
Sugarcane
ST
MOE
Day
0
NA
NA
55
27
NA
Days
For
ST
MOE
>
UF
NA
NA
3
7
NA
IT
30
Day
Avg
MOE
NA
NA
315
158
NA
Decid.
Fruit
Trees
ST
MOE
Day
0
1455
146
NA
49
NA
Days
For
ST
MOE
>
UF
0
0
NA
8
NA
IT
30
Day
Avg
MOE
4450
445
NA
148
NA
Evergreen
Fruit
Trees
ST
MOE
Day
0
582
58
19
NA
NA
Days
For
ST
MOE
>
UF
0
6
17
NA
NA
IT
30
Day
Avg
MOE
1780
178
59
NA
NA
Nut
Trees
ST
MOE
Day
0
NA
175
NA
35
NA
Days
For
ST
MOE
>
UF
NA
0
NA
11
NA
IT
30
Day
Avg
MOE
NA
534
NA
107
NA
Table
24:
Summary
of
Carbaryl
Noncancer
Postapplication
Worker
Risks
Crop
Group
Result
Type
Exposure
Descriptor
Very
Low
Low
Medium
High
Very
High
98
Turf/
Sod
ST
MOE
Day
0
NA
312
NA
10
NA
Days
For
ST
MOE
>
UF
NA
0
NA
14
NA
IT
30
Day
Avg
MOE
NA
1505
NA
46
NA
Root
Veg.
ST
MOE
Day
0
NA
245
49
29
NA
Days
For
ST
MOE
>
UF
NA
0
4
7
NA
IT
30
Day
Avg
MOE
NA
1322
264
159
NA
Cucurbit
Veg.
ST
MOE
Day
0
NA
147
49
29
NA
Days
For
ST
MOE
>
UF
NA
0
4
7
NA
IT
30
Day
Avg
MOE
NA
793
264
159
NA
Fruiting
Veg.
ST
MOE
Day
0
NA
147
105
74
NA
Days
For
ST
MOE
>
UF
NA
0
0
2
NA
IT
30
Day
Avg
MOE
NA
793
566
396
NA
Brassica
ST
MOE
Day
0
NA
37
18
15
NA
Days
For
ST
MOE
>
UF
NA
6
9
11
NA
IT
30
Day
Avg
MOE
NA
198
99
79
NA
Leafy
Veg.
ST
MOE
Day
0
NA
147
49
29
NA
Days
For
ST
MOE
>
UF
NA
0
4
7
NA
IT
30
Day
Avg
MOE
NA
793
264
159
NA
Stem/
stalk
Veg.
ST
MOE
Day
0
NA
137
82
41
NA
Days
For
ST
MOE
>
UF
NA
0
1
5
NA
IT
30
Day
Avg
MOE
NA
788
473
236
NA
Vine/
trellis
ST
MOE
Day
0
NA
147
74
15
7
Days
For
ST
MOE
>
UF
NA
0
2
11
14
IT
30
Day
Avg
MOE
NA
793
396
79
40
Nursery/
Ornamentals
ST
MOE
Day
0
NA
669
421
184
NA
Days
For
ST
MOE
>
UF
NA
0
0
0
NA
IT
30
Day
Avg
MOE
NA
3604
2266
991
NA
Chronic
MOE
NA
4399
2765
1210
NA
99
7.2.2
Occupational
Postapplication
Exposure
and
Risk
Estimates
for
Cancer
Cancer
risks
for
private
growers
(i.
e.,
10
exposures/
year)
and
commercial
farmworkers
(i.
e.,
30
exposures/
year)
were
calculated
for
different
crop
groups
as
described
above
and
summarized
in
Table
25
below.
Current
label
requirements
specify
12
hour
REIs.
For
all
scenarios,
cancer
risks
are
<1x10
4
on
the
day
of
application
(i.
e.,
at
the
current
REI).
Likewise,
cancer
risks
are
<1x10
6
on
the
day
of
application
for
most
crop/
activity
scenarios
with
private
growers
and
also
for
low
to
medium
exposures
for
commercial
farmworkers.
In
fact,
risks
for
all
scenarios
were
in
the
10
6
range
in
all
but
two
scenarios
for
commercial
farmworkers
participating
in
very
high
exposure
activities
(e.
g.,
sweetcorn
handharvesting)
on
the
day
of
application.
In
these
three
cases,
risks
were
in
the
10
5
range
on
the
day
of
application.
For
private
growers,
it
takes
approximately
5
days
for
risks
to
decline
to
<1x10
6
for
crop/
activity
combinations
that
exceed
1x10
6
on
the
day
of
application.
For
commercial
farmworkers,
it
takes
approximately
8
days
for
risks
to
reach
the
target
level
of
concern
of
<1x10
6
.
The
1996
Barolo
memo
which
focused
on
cancer
risk
management
should
be
considered
in
the
interpretation
of
these
results.
Current
label
requirements
appear
to
be
adequate
for
all
postapplication
cancer
risks
if
the
10
4
range
is
used
for
risk
management.
If
the
10
6
risk
range
is
considered,
it
also
appears
that
the
current
REI
appears
adequate
to
address
cancer
risks
for
many
crop/
activity
combinations.
However,
for
higher
exposure
situations,
longer
duration
REIs
are
predicted.
In
all
cases,
REIs
predicted
based
on
cancer
risks
are
less
restrictive
or
similar
(i.
e.,
within
a
day
or
two
for
commercial
farmworkers)
than
those
predicted
based
on
the
noncancer
effects
of
carbaryl.
In
no
cases
do
cancer
risks
indicate
more
restrictive
REIs
than
for
noncancer
risks
calculated
for
the
corresponding
crop/
activity
exposure
scenario.
Table
25:
Summary
of
Carbaryl
Cancer
Postapplication
Worker
Risks
Crop
Group
Result
Type
Exposure
Descriptor
(From
Policy
003)
Very
Low
Low
Medium
High
Very
High
Low
Berry
Private
Grower
Day
0
Risk
NA
1.7
x
10
7
NA
6.2x
10
7
NA
Private
Grower
Days
<
1x10
6
NA
0
NA
0
NA
Com..
Farmworker
Day
0
Risk
NA
5.0
x
10
7
NA
1.9x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
NA
4
NA
Bunch/
Bundle
Private
Grower
Day
0
Risk
NA
7.4
x
10
8
9.6x
10
7
1.5x
10
6
NA
Private
Grower
Days
<
1x10
6
NA
0
0
2
NA
Com..
Farmworker
Day
0
Risk
NA
2.2
x
10
7
2.9x
10
6
4.4x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
5
8
NA
Low
/Med.
Field/
Row
Crops
Private
Grower
Day
0
Risk
NA
3.1x
10
8
4.7x
10
7
7.8x
10
7
NA
Private
Grower
Days
<
1x10
6
NA
0
0
0
NA
Com..
Farmworker
Day
0
Risk
NA
9.3x
10
8
1.4x
10
6
2.3x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
2
5
NA
Table
25:
Summary
of
Carbaryl
Cancer
Postapplication
Worker
Risks
Crop
Group
Result
Type
Exposure
Descriptor
(From
Policy
003)
Very
Low
Low
Medium
High
Very
High
100
Tall
Field/
Row
Crops
Private
Grower
Day
0
Risk
NA
1.2
x
10
7
5.0
x
10
7
1.2
x
10
6
2.1
x
10
5
Private
Grower
Days
<
1x10
6
NA0
0
223
Com..
Farmworker
Day
0
Risk
NA
3.7
x
10
7
1.5
x
10
6
3.7
x
10
6
8.5
x
10
5
Com..
Farmworker
Days
<
1x10
6
NA
0
3
10
31
Cut
Flowers
Private
Grower
Day
0
Risk
NA
1.0
x
10
6
1.7
x
10
6
2.9
x
10
6
NA
Private
Grower
Days
<
1x10
6
NA
0
3
6
NA
Com..
Farmworker
Day
0
Risk
NA
3.1
x
10
6
5.0
x
10
6
8.7
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
6
9
12
NA
Sugarcane
Private
Grower
Day
0
Risk
NA
NA
5.6
x
10
7
1.1
x
10
6
NA
Private
Grower
Days
<
1x10
6
NA
NA
0
1
NA
Com..
Farmworker
Day
0
Risk
NA
NA
1.7
x
10
6
3.3
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
NA
3
6
NA
Decid.
Fruit
Trees
Private
Grower
Day
0
Risk
2.1
x
10
8
2.1
x
10
7
NA
6.3
x
10
7
NA
Private
Grower
Days
<
1x10
6
0
0NA0NA
Com..
Farmworker
Day
0
Risk
6.3
x
10
8
6.3
x
10
7
NA
1.9
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
0
0NA6NA
Evergreen
Fruit
Trees
Private
Grower
Day
0
Risk
5.2
x
10
8
5.2
x
10
7
1.6
x
10
6
NA
NA
Private
Grower
Days
<
1x10
6
0
0
5
NA
NA
Com..
Farmworker
Day
0
Risk
1.6
x
10
7
1.6
x
10
6
4.7
x
10
6
NA
NA
Com..
Farmworker
Days
<
1x10
6
0
5
16
NA
NA
Nut
Trees
Private
Grower
Day
0
Risk
NA
1.7
x
10
7
NA
8.7
x
10
7
NA
Private
Grower
Days
<
1x10
6
NA
0
NA
0
NA
Com..
Farmworker
Day
0
Risk
NA
5.7
x
10
7
NA
2.6
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
NA
10
NA
Turf/
Sod
Private
Grower
Day
0
Risk
NA
8.1
x
10
8
NA
2.7
x
10
6
NA
Private
Grower
Days
<
1x10
6
NA
0
NA
2
NA
Com..
Farmworker
Day
0
Risk
NA
2.4
x
10
7
NA
8.0
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
NA
4
NA
Table
25:
Summary
of
Carbaryl
Cancer
Postapplication
Worker
Risks
Crop
Group
Result
Type
Exposure
Descriptor
(From
Policy
003)
Very
Low
Low
Medium
High
Very
High
101
Root
Veg.
Private
Grower
Day
0
Risk
NA
1.2
x
10
7
6.2
x
10
7
1.0
x
10
6
NA
Private
Grower
Days
<
1x10
6
NA
0
0
0
NA
Com..
Farmworker
Day
0
Risk
NA
3.7
x
10
7
1.9
x
10
6
3.1
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
4
6
NA
Cucurbit
Veg.
Private
Grower
Day
0
Risk
NA
2.1
x
10
7
6.2
x
10
7
1.0
x
10
6
NA
Private
Grower
Days
<
1x10
6
NA
0
0
0
NA
Com..
Farmworker
Day
0
Risk
NA
6.2
x
10
7
1.9
x
10
6
3.1
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
4
6
NA
Fruiting
Veg.
Private
Grower
Day
0
Risk
NA
2.1
x
10
7
2.9
x
10
7
4.1
x
10
7
NA
Private
Grower
Days
<
1x10
6
NA
0
0
0
NA
Com..
Farmworker
Day
0
Risk
NA
6.2
x
10
7
8.7
x
10
7
1.2
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
0
1
NA
Brassica
Private
Grower
Day
0
Risk
NA
8.3
x
10
7
1.7
x
10
6
2.1
x
10
6
NA
Private
Grower
Days
<
1x10
6
NA
0
3
4
NA
Com..
Farmworker
Day
0
Risk
NA
2.5
x
10
6
5.0
x
10
6
6.2
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
5
9
10
NA
Leafy
Veg.
Private
Grower
Day
0
Risk
NA
2.1
x
10
7
6.2
x
10
7
1.0
x
10
6
NA
Private
Grower
Days
<
1x10
6
NA
0
0
0
NA
Com..
Farmworker
Day
0
Risk
NA
6.2
x
10
7
1.9
x
10
6
3.1
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
4
6
NA
Stem/
stalk
Veg.
Private
Grower
Day
0
Risk
NA
2.2
x
10
7
3.7
x
10
7
7.4
x
10
7
NA
Private
Grower
Days
<
1x10
6
NA
0
0
0
NA
Com..
Farmworker
Day
0
Risk
NA
6.7
x
10
7
1.1
x
10
6
2.2
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
1
4
NA
Vine/
trellis
Private
Grower
Day
0
Risk
NA
2.1
x
10
7
4.1
x
10
7
2.1
x
10
6
4.1
x
10
6
Private
Grower
Days
<
1x10
6
NA0
0
48
Com..
Farmworker
Day
0
Risk
NA
6.2
x
10
7
1.2
x
10
6
6.2
x
10
6
1.2
x
10
5
Com..
Farmworker
Days
<
1x10
6
NA
0
1
10
13
Table
25:
Summary
of
Carbaryl
Cancer
Postapplication
Worker
Risks
Crop
Group
Result
Type
Exposure
Descriptor
(From
Policy
003)
Very
Low
Low
Medium
High
Very
High
102
Nursery/
Ornamentals
Private
Grower
Day
0
Risk
NA
4.5
x
10
8
7.2
x
10
8
1.7
x
10
7
NA
Private
Grower
Days
<
1x10
6
NA
0
0
0
NA
Com..
Farmworker
Day
0
Risk
NA
1.4
x
10
7
2.2
x
10
7
5.0
x
10
7
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
0
0
NA
7.3
Occupational
Risk
Characterization
Characterization
of
the
occupational
risks
is
included
below
for
both
handlers
and
for
postapplication
exposures.
Handlers:
The
occupational
handler
assessment
for
carbaryl
is
complex
in
that
three
different
types
of
noncancer
risk
calculations
were
required
based
on
the
recently
selected
endpoints.
The
durations
of
exposure
that
were
considered
for
noncancer
toxicity
were
short
term
(
30
days),
intermediate
term
(30
days
up
to
several
months),
and
chronic
(every
working
day).
A
complete
array
of
calculations
was
completed
for
all
identified
exposure
scenarios
using
the
short
and
intermediateterm
endpoints
because
the
Agency
believes
that
carbaryl
uses
fit
the
criteria
for
both
of
these
durations.
The
only
calculations
that
were
completed
using
the
chronic
endpoint
were
limited
and
those
associated
with
the
greenhouse
and
floriculture
industries
where
these
kinds
of
exposures
may
occur.
Cancer
risks
were
also
calculated
using
a
linear,
low
dose
extrapolation
model
(i.
e.,
Q1*)
for
both
private
growers
(i.
e.,
10
application
days
per
year)
and
for
those
who
may
more
actively
use
carbaryl
such
as
a
commercial
applicator
(i.
e.,
30
application
days
per
year).
Cancer
calculations
were
completed
as
well
for
every
scenario
that
has
been
identified
for
both
private
growers
and
commercial
applicators.
For
all
of
the
different
types
of
endpoints
selected
(except
chronic
where
a
limited
number
of
calculations
were
completed),
the
Agency
identified
exposures
that
fit
into
28
different
scenarios
which
are
defined
based
on
the
equipment
used
to
make
applications
or
the
type
of
formulation
used.
Within
each
of
these
categories,
different
application
rates
and
acres
treated
values
were
considered
to
evaluate
the
broad
range
of
applications
that
may
occur
with
each
kind
of
equipment
(e.
g.,
a
groundboom
may
be
used
for
turf
or
agriculture).
All
totaled,
128
different
crop/
rate/
acres
combinations
were
considered
within
the
28
scenarios
for
the
short
and
intermediate
term
toxicity
categories
plus
4
chronic
crop/
rate/
acre
combinations.
The
overall
result
is
that
4
sets
of
128
calculations
each
(516
total
calculations)
were
completed
for
occupational
carbaryl
handlers.
Finally,
it
should
be
noted
that
each
calculation
was
completed
at
different
levels
of
personal
protection
to
allow
for
a
more
informed
risk
management
decision.
Even
given
the
scope
of
the
calculations
that
have
already
been
completed,
it
is
likely
that
there
are
some
uses
of
carbaryl
that
have
not
been
quantitatively
addressed
in
this
document
either
through
lack
of
exposure
data
or
other
information
and
because
carbaryl
is
such
a
widely
used
chemical.
These
scenarios
will
be
addressed
by
the
Agency
when
they
are
identified
as
carbaryl
progresses
through
the
reregistration
process.
Readers
are
also
encouraged
to
evaluate
novel
scenarios
by
considering
the
range
of
estimates
already
completed
as
it
is
likely
that
many
uses
could
be
quantitatively
assessed
by
reviewing
those
calculations
as
a
wide
array
of
chemical
use
combinations
and
equipment
types
have
already
been
considered.
103
The
data
that
were
used
in
the
carbaryl
occupational
handler
risk
assessment
represent
the
best
data
and
approaches
that
are
currently
available.
While
some
of
the
data
which
have
been
used
may
not
be
of
optimal
quality,
they
represent
the
best
available
data
for
the
scenario
in
question.
In
many
cases,
the
Pesticide
Handlers
Exposure
Database
(PHED)
was
used
to
develop
the
unit
exposure
values.
The
quality
of
the
data
included
in
PHED
vary
widely
from
scenarios
that
meet
guideline
requirements
for
studies
to
others
where
a
limited
number
of
poor
quality
datapoints
are
available.
The
results
for
each
scenario
should
be
reviewed
in
the
context
of
the
quality
of
these
data.
In
addition
to
PHED,
the
Agency
used
a
number
of
studies
to
define
unit
exposure
values.
Generally,
the
quality
of
these
studies
is
excellent.
Most,
except
for
the
trigger
sprayer
data,
are
very
recent
and
based
on
the
newest
analytical
requirements
and
monitoring
techniques.
PHED
unit
exposure
values
represent
a
central
tendency
of
the
data
(i.
e.,
geometric
mean,
median
or
arithmetic
mean
depending
upon
the
distribution
of
the
data).
As
such,
the
values
based
on
the
recent
studies
also
are
measures
of
central
tendency
(e.
g.,
the
geometric
means
were
selected
from
each
study
for
assessment
purposes
in
most
cases).
Along
with
the
unit
exposure
values
used
in
the
assessment,
other
inputs
include
application
rates
and
daily
acres
treated
values.
Selected
application
rates
represent
a
range
for
each
major
market
in
which
carbaryl
is
used
including
agriculture,
turf
(lawncare,
golf
courses,
etc.),
ornamentals,
and
for
wide
area
applications
such
as
mosquito
control.
Many
application
rates
also
represent
maximum
amounts
that
are
allowed
by
the
label
for
certain
settings.
Where
available,
average
use
rates
were
also
used
to
provide
for
a
more
informed
risk
management
decision.
The
application
rates
that
were
selected
for
use
in
the
risk
assessment
were
defined
based
on
labels,
information
provided
by
the
Aventis
Crop
Science
at
the
September
24,
1998
SMART
Meeting
for
carbaryl,
and
based
on
various
analyses
of
carbaryl
use
patterns
completed
by
the
Agency's
Biological
and
Economic
Analysis
Division.
The
other
key
input
for
completing
handler
risk
assessments
used
for
defining
how
much
chemical
can
be
used
in
a
day
is
how
much
can
be
treated
in
a
day
which
is
generally
expressed
as
the
number
of
acres
treated
per
day.
The
values
that
were
used
for
this
parameter
represent
the
latest
Agency
thinking
on
this
issue.
In
fact,
the
Science
Advisory
Council
For
Exposure
recently
updated
the
policy
for
these
inputs
(July
2000
Exposure
SAC
Policy
9:
Standard
Values
for
Daily
Acres
Treated
in
Agriculture).
These
most
recent
values
have
been
used
for
the
calculations.
In
addition
to
the
key
sources
of
information
considered
above,
there
are
many
underlying
factors
that
may
impact
the
overall
results
of
a
risk
assessment.
For
example,
the
protection
factors
used
for
adding
additional
levels
of
dermal
and
respiratory
protection
may
impact
the
overall
risk
picture.
The
factors
used
in
this
assessment
by
the
Agency
are
the
ones
that
have
been
used
for
several
years.
Other
such
factors
may
include
the
fact
that
average
application
rates
have
been
generally
used
to
represent
typical
application
rates
to
calculate
ranges
of
risks
when
it
is
clear
that
the
two
values
could
differ
greatly.
The
Agency
has
taken
this
approach
because
the
data
required
to
define
typical
application
rates
within
each
crop
are
generally
unavailable.
There
are
also
exposure
monitoring
issues
that
should
be
considered.
For
example,
in
many
cases
the
data
included
in
PHED
are
based
on
the
use
of
cotton
gloves
for
hand
exposure
monitoring
which
are
thought
by
many
to
overestimate
exposure
because
they
potentially
retain
residues
more
than
human
skin
would
over
time
(i.
e.,
they
may
act
like
a
sponge
compared
to
the
actual
hand).
A
similar
issue
was
noted
with
the
carbaryl
specific
dog
grooming
study
that
used
the
handwash
approach
to
monitor
exposure
after
shampooing
several
dogs.
These
intangible
elements
of
the
risk
assessment
reflect
many
of
the
hidden
uncertainties
associated
with
exposure
data.
The
overall
impacts
of
these
uncertainties
is
hard
to
quantify.
The
factor
to
again
consider
is
that
the
Agency
used
the
best
available
data
to
complete
the
risk
assessment
for
carbaryl.
In
summary,
the
Agency
believes
that
the
risk
values
presented
in
this
occupational
assessment
104
represent
the
highest
quality
results
that
could
be
produced
given
the
exposure,
use,
and
toxicology
data
that
are
available.
Certainly
risk
managers
and
other
interested
parties
should
consider
the
quality
of
individual
inputs
when
interpreting
the
results
and
make
decisions
accordingly.
It
is
difficult
to
ascertain
where
on
a
distribution
the
values
which
have
been
calculated
fall
because
the
distributional
data
for
exposure,
application
rates,
acres
treated
and
many
other
parameters
are
unrefined.
The
Agency
does
believe,
however,
that
the
risks
represent
conservative
estimates
of
exposure
because
maximum
application
rates
are
coupled
with
large
acreage
estimates
to
define
risk
estimates
that
likely
fall
in
the
upper
percentiles
of
the
actual
exposure
distributions.
Additionally,
risk
estimates
are
thought
to
be
conservative
even
when
measures
of
central
tendency
are
combined
because
values
that
would
be
considered
to
be
in
the
lower
percentile
aspect
of
any
input
parameter
have
not
been
used
in
the
calculations.
Postapplication:
Like
the
occupational
handler
risk
assessment
discussed
above,
the
postapplication
worker
risk
assessment
for
carbaryl
is
also
complex
in
that
three
different
types
of
noncancer
risk
calculations
were
required
based
on
the
recently
selected
endpoints
along
with
cancer
risk
calculations
using
a
linear,
low
dose
extrapolation
model.
For
all
of
the
different
types
of
endpoints
selected
(except
chronic
where
a
limited
number
of
calculations
were
completed),
the
Agency
identified
exposures
that
fit
into
18
different
crop
groups
which
are
defined
essentially
based
on
the
nature
of
the
crop
where
a
work
activity
would
take
place.
Within
each
of
these
crop
groups,
ranges
of
transfer
coefficients
were
considered
to
reflect
differences
in
exposures
that
would
be
associated
with
the
variety
of
cultural
practices
that
are
required
to
produce
the
crop/
product.
All
totaled,
54
different
cultural
practices
were
considered
within
the
18
crop
groups
for
each
toxicity
category.
The
overall
result
is
that
4
sets
of
54
calculations
each
(216
plus
a
few
chronic
values)
were
completed
for
postapplication
workers.
Finally,
it
should
be
noted
that
each
calculation
was
completed
at
different
days
after
application
to
reflect
residue
dissipation
over
time
in
the
environment
and
to
allow
for
a
more
informed
risk
management
decision.
Even
given
the
scope
of
the
calculations
that
have
already
been
completed,
it
is
likely
that
there
are
some
uses
of
carbaryl
that
have
not
been
quantitatively
addressed
in
this
document
either
through
lack
of
exposure
data
or
other
information
and
because
carbaryl
is
such
a
widely
used
chemical.
These
scenarios
will
be
addressed
by
the
Agency
when
they
are
identified
as
carbaryl
progresses
through
the
reregistration
process.
Readers
are
also
encouraged
to
evaluate
novel
scenarios
by
considering
the
range
of
estimates
already
completed
as
it
is
likely
that
many
uses
could
be
quantitatively
assessed
by
reviewing
existing
calculations
as
a
wide
array
of
crop/
activity
combinations
have
already
been
considered.
The
data
that
were
used
in
the
carbaryl
postapplication
worker
risk
assessment
represent
the
best
data
and
approaches
that
are
currently
available.
The
latest
Agency
transfer
coefficient
values
have
been
used
to
complete
this
assessment
including
the
recently
submitted
ARTF
studies
on
greenhouse
workers.
Most
of
the
values
in
the
current
Agency
policy
are
based
on
the
work
of
the
Agricultural
Reentry
Task
Force
(ARTF)
of
which,
Aventis
Crop
Science
is
a
member.
The
current
Agency
policy
is
interim
in
nature
but
represents
all
of
the
data
that
have
been
submitted
by
the
ARTF
and
evaluated
by
the
Agency.
The
work
of
the
ARTF
is
still
ongoing
so
additional
data
may
become
available
to
refine
the
exposure
estimates
as
more
data
are
submitted
to
the
Agency.
Also,
it
is
possible
that
there
are
exposure
scenarios
that
have
not
been
addressed
by
the
Agency
because
the
transfer
coefficient
model
is
not
appropriate
as
there
is
little
or
no
foliar
contact
associated
with
the
activity.
There
are
also
potentially,
partially
mechanized
activities
that
could
lead
to
exposure
where
the
Agency
has
no
information.
These
will
need
to
be
carefully
considered
in
the
reregistration
process.
In
addition
to
the
exposure
inputs
for
specific
activities
(i.
e.,
transfer
coefficients),
the
Agency
used
4
carbaryl
specific
105
DFR
(Dislodgeable
Foliar
Residue)
dissipation
studies
and
a
single
TTR
(Turf
Transferable
Residue)
study
to
calculate
risks
for
all
postapplication
workers
in
every
region
in
the
country.
It
is
standard
practice
for
the
Agency
to
use
these
kinds
of
studies
in
this
manner
but
it
is
likely
that
additional
cropand
region
specific
data
could
be
used
to
further
refine
the
risk
assessment.
Several
other
key
pieces
of
data
and
information
were
considered
in
the
development
of
the
postapplication
risk
values
including
use
and
usage
information
and
exposure
frequency
in
the
cancer
risk
assessment.
For
many
agricultural
crops,
the
maximum
application
rate
is
low
(e.
g.,
1.5
to
2
lb
ai/
acre)
in
many
crops.
As
a
result,
postapplication
risks
were
generally
calculated
at
maximum
rate
levels
because
of
the
already
inherent
complexity
of
the
assessment
and
because
it
is
likely
that
results
may
not
be
extremely
sensitive
to
changes
in
this
value.
In
addition
to
the
key
sources
of
information
considered
above,
there
are
many
underlying
factors
that
may
impact
the
overall
results
of
a
risk
assessment.
For
example,
subtle
differences
between
activities
in
similar
crops
within
each
of
the
18
agronomic
groups
considered
in
the
assessment
may
not
be
accurately
reflected
in
the
current
transfer
coefficient
values.
The
use
of
4
DFR
studies
to
represent
all
crops
and
all
regions
within
the
country
could
lead
to
results
that
do
not
reflect
actual
use
practices
and
conditions
in
some
parts
of
the
country.
Additionally,
the
exposure
frequency
values
that
were
used
for
private
growers
and
professional
farmworkers
tend
to
be
supported
by
available
data
but
could
be
refined
if
data
on
work
patterns
and
regional
carbaryl
use
becomes
available.
As
with
the
handler
assessment
above,
the
intangible
elements
reflect
many
of
the
hidden
uncertainties
associated
with
exposure
data.
The
overall
impacts
of
these
uncertainties
is
hard
to
quantify.
The
factor
to
again
consider
is
that
the
Agency
used
the
best
available
data
to
complete
the
risk
assessment
for
carbaryl.
In
summary,
the
Agency
believes
that
the
risk
values
presented
in
this
postapplication
assessment
represent
the
highest
quality
results
that
could
be
produced
given
the
exposure,
use,
and
toxicology
data
that
are
available.
Certainly
risk
managers
and
other
interested
parties
should
consider
the
quality
of
individual
inputs
when
interpreting
the
results
and
make
decisions
accordingly.
It
is
difficult
to
ascertain
where
on
a
distribution
the
values
which
have
been
calculated
fall
because
the
distributional
data
for
exposure,
residue
dissipation
and
many
other
parameters
are
unrefined.
The
Agency
does
believe,
however,
that
the
risks
represent
conservative
estimates
of
exposure
because
maximum
application
rates
are
used
to
define
residue
levels
upon
which
the
risk
calculations
are
based.
Additionally,
risk
estimates
are
thought
to
be
conservative
even
when
measures
of
central
tendency
(e.
g.,
most
transfer
coefficients
are
thought
to
be
central
tendency)
are
used
because
values
that
would
be
considered
to
be
in
the
lower
percentile
aspect
of
any
input
parameter
have
not
been
used
in
the
calculations.
8.0
HUMAN
AND
DOMESTIC
ANIMAL
INCIDENT
DATA
REVIEW
Data
on
incidents
of
adverse
reactions
in
humans
exposed
to
carbaryl
were
evaluated
from
several
sources,
including
OPP's
Incident
Data
System,
Poison
Control
Centers,
California
Department
of
Pesticide
Regulation,
National
Pesticide
Telecommunications
Network
and
the
open
literature.
The
data
from
the
Incident
Data
System
indicated
that
a
majority
of
cases
from
carbaryl
exposure
involved
dermal
reactions.
A
number
of
cases
involved
asthmatics
and
people
who
experienced
hives
and
other
106
allergic
type
reactions.
According
to
California
data,
about
half
of
the
cases
involved
skin
and
eye
effects
in
handlers.
About
a
quarter
of
the
skin
reactions
were
due
to
workers
that
were
exposed
to
residues
on
crops.
Reports
from
the
literature
are
very
limited
but
tend
to
support
the
finding
that
carbaryl
has
irritant
properties.
The
Poison
Control
Center
cases
involving
non
occupational
adults
and
older
children
showed
an
increased
risk
in
five
of
the
six
measures
reported.
These
cases
were
almost
twice
as
likely
to
require
serious
health
care
(hospitalization
or
treatment
in
a
critical
care
unit)
and
were
two
and
a
half
times
more
likely
to
experience
major
medical
outcome
(life
threatening
effects
or
significant
residual
disability)
as
compared
to
other
pesticides.
This
pattern
of
increased
risk
was
not
seen
among
occupational
reports
or
in
young
children.
This
may
mean
careless
handling
by
non
professionals
is
a
particular
hazard.
Five
case
reports
suggested
that
carbaryl
may
be
a
cause
of
chronic
neurological
or
psychological
problems.
Some
of
these
effects
appear
to
be
consistent
with
those
reported
from
organophosphate
poisoning.
However,
unlike
organophosphates,
no
controlled
studies
have
been
undertaken.
If
such
effects
occur
as
a
result
of
over
exposure
to
carbaryl,
they
appear
to
be
relatively
rare.
The
effects
reported
among
the
five
case
reports
are
too
inconsistent
to
draw
any
conclusions,
but
do
suggest
the
need
for
further
study.
Carbaryl
appears
capable
of
causing
dermal
and
allergic
type
reactions.
Data
support
the
need
for
personal
protective
equipment
and
eye
protection
for
handlers
for
field
workers
who
may
have
extensive
exposure
to
carbaryl.
Labels
for
products
should
advise
that
carbaryl
can
cause
sensitizing
effects
in
some
people.
Based
on
an
evaluation
of
limited
incident
data
on
domestic
animals
in
IDS,
it
is
recommended
that
all
labels
for
carbaryl
products
used
on
cats
contain
the
age
restriction
stated
in
PR
Notice
96
6
(should
not
be
used
in
kittens
less
than
12
weeks
of
age).
A
detailed
discussion
of
the
incident
data
is
presented
in
Appendix
2.
9.0
DATA
NEEDS
Toxicology
data
gaps
°
90
day
inhalation
study
in
rats
with
cholinesterase
measurements
Product
chemistry
data
gaps
°
A
review
of
the
labels
and
supporting
residue
data
indicate
that
several
label
amendments
are
required.
Details
are
provided
in
the
Product
and
Residue
Chemistry
Chapters
(DP
Barcode:
D240989)
dated
November
14,
2000.
°
The
requirement
for
acceptable
enforcement
methods
which
determine
residues
of
concern
in
plant
and
livestock
commodities
remains
outstanding.
°
The
requirements
for
storage
stability
data
are
not
satisfied
for
purposes
of
reregistration.
107
Additional
data
are
required
depicting
the
storage
stability
of
carbaryl
per
se
in
an
oilseed,
processed
commodities
of
an
oily
crop,
and
a
dried
fruit
stored
for
up
to
10
months.
In
addition,
the
registrant
is
relying
on
earlier
magnitude
of
the
residue
studies
that
are
not
supported
by
the
existing
storage
stability
data;
therefore,
additional
storage
stability
data
are
required.
The
required
data
must
reflect
storage
intervals
of
18
months
for
alfalfa
commodities,
15
months
for
potatoes,
17
months
for
cottonseed,
22
months
for
wheat
commodities,
and
33
months
for
rangeland
grass.
In
addition,
if
the
registrant
wishes
to
rely
on
the
previously
submitted
sugar
beet
processing
study,
information
pertaining
to
sample
conditions
and
intervals
for
the
study
must
be
submitted.
°
For
the
purpose
of
reregistration,
the
requirements
for
storage
stability
data
for
carbaryl
residues
in
livestock
commodities
are
partially
satisfied.
Additional
information
on
the
storage
intervals
prior
to
analysis
for
metabolite
residues
in
the
cattle
feeding
study
is
required.
°
Separate
tolerances
on
many
commodities
need
to
be
reassigned
concomitant
with
establishing
tolerances
for
the
appropriate
crop
group
and
subgroup.
The
recommended
changes
are
summarized
in
Table
C
under
"Tolerances
Needed
Under
40
CFR
§180.169(
a),
crop
group/
subgroup
tolerances"
of
the
Product
and
Residue
Chemistry
Chapters.
°
The
data
submitted
are
not
adequate
to
support
the
use
of
granular
(G)
formulations
of
carbaryl
on
leafy
vegetables.
Residues
of
carbaryl
found
in
leaf
lettuce
were
not
consistent.
Both
samples
of
lettuce
from
the
10%
G
treatment
had
substantially
higher
residues
(37.01
and
47.22
ppm)
than
one
of
the
samples
treated
with
the
FlC
(23.25
ppm).
Additionally,
all
residues
were
significantly
above
the
current
tolerance
of
10
ppm
and
all
residue
data
submitted
in
support
of
the
tolerance
in
lettuce
(<
8.85
ppm).
No
explanation
for
the
higher
residues
was
given
by
the
registrant.
The
registrant
may
elect
to
repeat
the
side
by
side
trial
on
leaf
lettuce
again
or
submit
a
rationale
for
the
results
of
the
leaf
lettuce
study.
°
Data
are
required
depicting
residues
of
carbaryl
in/
on
grass
forage
harvested
immediately
(0
day)
following
the
last
of
two
applications
of
carbaryl
(WP
or
FlC)
at
1.5
lb
ai/
A
to
pasture.
A
total
of
12
field
trials
are
required
in
areas
throughout
the
U.
S.
°
Adequate
data
are
available
to
reassess
the
tolerances
for
residues
of
carbaryl
in/
on
dried
beans,
cowpeas,
lentils
and
peas
with
pods.
These
data
support
the
establishment
of
crop
subgroup
tolerances
for
edible
podded
legume
vegetables
(6A),
and
for
dried,
shelled
pea
and
bean
except
soybean
(6C).
However,
additional
residue
data
are
required
if
the
registrant
seeks
tolerances
for
residues
in/
on
succulent,
shelled
pea
and
bean
commodities.
A
total
of
12
tests,
six
tests
each
on
a
succulent,
shelled
cultivar
of
bean
and
garden
pea,
are
required
to
support
a
tolerance
for
residues
in/
on
the
succulent,
shelled
pea
and
bean
crop
subgroup
(6B).
The
registrant
is
referred
to
OPPTS
GLN
860.1500
for
the
number
and
distribution
of
tests
required.
108
°
Adequate
data
are
available
to
reassess
the
tolerance
for
wheat
forage
and
straw.
However,
the
Agency
now
considers
wheat
hay
a
significant
RAC
for
feed
purposes
(OPPTS
GLN
860.1000
Table
1.).
A
full
set
of
20
field
trials
as
specified
in
OPPTS
GLN
860.1500
are
required
depicting
carbaryl
residues
in/
on
wheat
hay.
When
all
the
field
trials
are
complete,
PHIs
and
tolerances
for
hay
based
on
the
field
trial
data
should
be
proposed.
Data
on
wheat
hay
will
be
translatable
to
proso
millet
hay.
°
Adequate
residue
data
are
available
on
olives
provided
that
use
directions
for
olives
are
amended
to
remove
the
statement
allowing
the
use
of
summer
oil
as
an
adjuvant.
Alternatively,
two
additional
field
trials
are
required
supporting
the
use
of
a
carbaryl
summer
oil
tank
mix.
°
The
registrant
intends
to
support
a
tolerance
for
residues
of
carbaryl
in/
on
imported
pineapples
(Aventis
Crop
Science
personal
communication
with
C.
Olinger,
9/
24/
98
SMART
meeting).
Residue
data
are
required
depicting
residues
in/
on
pineapples
following
application
of
carbaryl
at
the
maximum
use
rate
and
minimum
PHI.
Five
trials
must
be
submitted,
three
from
Costa
Rica
and
two
from
Mexico.
°
Additional
data
are
required
depicting
carbaryl
residues
in/
on
cotton
gin
byproducts
derived
from
cotton
treated
at
the
maximum
labeled
rate
and
harvested
28
days
after
the
final
application
using
commercial
equipment
(stripper
and
mechanical
picker).
At
least
three
field
trials
representing
each
type
of
harvesting
(stripper
and
picker)
are
required.
°
The
registrant
does
not
intend
to
support
carbaryl
uses
on
avocados,
barley,
maple
sap,
oats,
rye,
and
sweet
sorghum;
however,
IR
4
has
indicated
(Correspondence
from
K.
Dorschner,
IR
4
Project,
9/
15/
94)
that
they
may
fulfill
the
residue
data
requirements
for
some
of
these
commodities.
These
data
have
not
been
submitted.
°
The
reregistration
requirements
for
magnitude
of
the
residue
in
livestock
commodities
are
not
fulfilled.
Additional
data
are
required
to
support
dermal
and
poultry
house
uses.
Occupational/
Residential
Exposure
Data
Gaps
Residential
Exposure
°
For
the
postapplication
risk
assessments,
there
are
no
data
on
the
amount
of
residues
transferrable
from
treated
pets
to
humans.
Additional
residue
data
on
turf
would
help
refine
the
hand
to
mouth
and
object
to
mouth
toddler
exposures.
Occupational
Exposure
°
For
the
occupational
handler
risk
assessments,
several
exposure
data
gaps
were
identified,
including:
dust
use
for
animal
grooming
and
in
agriculture;
various
specialized
hand
equipment
application
methods
(e.
g.,
powered
backpack,
power
hand
fogger,
and
tree
injection);
and
nursery
operations
such
as
seedling
dips.
109
°
For
occupational
postapplication
risk
assessments,
several
data
gaps
exist,
such
as
an
incomplete
dislodgeable
foliar
residue
database
and
a
lack
of
exposure
data
on
partially
mechanized
cultural
practices
where
there
is
a
potential
for
exposure.
°
There
are
also
many
kinds
of
mechanized
activities
that
do
not
involve
foliar
contact
that
have
not
been
addressed
in
this
risk
assessment.
The
scenarios
include:
transplanting
many
crops
including
in
the
ornamental
and
forestry
industry;
thinning
some
crops
such
as
hops;
some
partially
mechanized
operations
that
also
involve
human
contact
(e.
g.,
cotton
harvesting
where
module
builders
and
trampers
are
used);
hand
weeding
some
crops
such
as
wheat;
various
operations
with
Christmas
trees
such
as
pruning
or
baling;
and
various
operations
with
nut
production
such
as
sweeping
for
harvest.
APPENDIX
1:
Toxicology
Profile
Appendix
1/
Table
1:
Toxicology
Profile
of
Carbaryl
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
870.3100
90
Day
oral
toxicity
rodents
N/
A
870.3150
90
Day
oral
toxicity
in
nonrodents
N/
A
870.3200
21/
28
Day
dermal
toxicity
with
technical
carbaryl
45630601(
2002)
acceptable/
nonguideline
0,
20,
50,
100
mg/
kg/
day
systemic
NOAEL
=
20
mg/
kg/
day
systemic
LOAEL
=
50
mg/
kg/
day
based
on
decreased
RBC
cholinesterase
in
males
and
females
and
brain
cholinesterase
in
males
dermal
NOAEL
=
100
mg/
kg/
day
dermal
LOAEL
not
established
870.3200
21/
28
Day
dermal
toxicity
with
Sevin®
XLR
Plus
(44.82%
a.
i.)
45630602
(2002)
unacceptable/
nonguideline
0,
20,
50,
100
mcL/
kg/
day
(0,
9.6,
24,
48
mg/
kg/
day)
systemic
NOAEL
=
50
mcL/
kg/
day
(24
mg/
kg/
day)
systemic
LOAEL
=
100
mcL/
kg/
day
(48
mg/
kg/
day)
based
on
decreased
body
weight
gain
dermal
NOAEL
=
100
mcL/
kg/
day
(48
mg/
kg/
day)
dermal
LOAEL
not
established
870.3200
21/
28
Day
dermal
toxicity
with
Sevin®
80S
(80.07%
a.
i.)
45630603
(2002)
unacceptable/
nonguideline
0,
20,
50,
100
mg/
kg/
day
systemic
NOAEL
=
20
mg/
kg/
day
systemic
LOAEL
=
50
mg/
kg/
day
based
on
decreased
RBC
cholinesterase
in
males
and
females
dermal
NOAEL
=
100
mg/
kg/
day
dermal
LOAEL
not
established
870.3250
90
Day
dermal
toxicity
N/
A
870.3465
90
Day
inhalation
toxicity
N/
A
870.3700a
Prenatal
developmental
in
rats
44732901
(1998)
acceptable/
guideline
0,
1,
4,
30
mg/
kg/
day
(oral
gavage)
Maternal
NOAEL
=
4
mg/
kg/
day
LOAEL
=
30
mg/
kg/
day
based
on
clinical
signs,
decreased
body
weight
gain
(BWG)
and
food
consumption
Developmental
NOAEL
=
4
mg/
kg/
day
LOAEL
=
30
mg/
kg/
day
based
on
decreased
fetal
body
weight
and
incomplete
ossification
of
multiple
bones
870.3700b
Prenatal
developmental
in
rabbits
44904202
(1999)
Acceptable/
guideline
0,
5,
50,
150
mg/
kg/
day
(oral
gavage)
Maternal
NOAEL
=
5
mg/
kg/
day
LOAEL
=
50
mg/
kg/
day
based
on
decreased
BWG
and
plasma
cholinesterase
inhibition
(ChEI)
Developmental
NOAEL
=
50
mg/
kg/
day
LOAEL
=
150
mg/
kg/
day
based
on
decreased
fetal
weight
Appendix
1/
Table
1:
Toxicology
Profile
of
Carbaryl
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
870.3800
Reproduction
and
fertility
effects
45448101
(2001)
acceptable/
guideline
0,
75,
300,
1500
ppm
(4.67,
31.34,
and
92.43
mg/
kg/
day
for
F0
males;
0,
5.56,
36.32,
and
110.78
mg/
kg/
day
for
F0
females;
0,
5.79,
23.49,
and
124.33
mg/
kg/
day
for
F1
males;
and
0,
6.41,
26.91,
and
135.54
mg/
kg/
day
for
F1
females
averaged
over
the
premating
period)
Parental
NOAEL
=
300
ppm
(23.49
31.34
mg/
kg/
day
for
males
and
26.91
36.32
mg/
kg/
day
for
females)
Parental
LOAEL
=
1500
ppm
(92.43
124.33
mg/
kg/
day
for
males
and
110.78
135.54
mg/
kg/
day
for
females)
based
on
decreased
body
weight,
weight
gain,
and
feed
consumption
Reproductive
toxicity
NOAEL
is
$
1500
ppm
(92.43
124.33
mg/
kg/
day
for
males
and
110.78
135.54
mg/
kg/
day
for
females)
Reproductive
toxicity
LOAEL
not
be
established
Offspring
NOAEL
=
75
ppm
(4.67
5.79
mg/
kg/
day
for
males
and
5.56
6.41
mg/
kg/
day
for
females).
Offspring
LOAEL
=
300
ppm
(23.49
31.34
mg/
kg/
day
for
males
and
26.91
36.32
mg/
kg/
day
for
females)
based
on
increased
numbers
of
F2
pups
with
no
milk
in
the
stomach
and
decreased
pup
survival.
870.4100a
Chronic
toxicity
in
rodents
N/
A
870.4100b
Chronic
toxicity
in
dogs
40166701
(1987)
0,
125,
400,
1250
ppm
(0,
3.1,
10,
31.3
mg/
kg/
day)
42022801
(1991)
0,
20,
45,
125
ppm
(5
weeks)
(M:
0,
0.59,
1.43,
3.83;
F:
0,
0,64,
1.54,
4.11
mg/
kg/
day)
Together,
the
studies
are
Acceptable/
guideline
MRID
40166701:
NOAEL
=
not
established
in
females
LOAEL
=
125
ppm
based
based
on
plasma
and
brain
ChEI
MRID
42022801:
NOAEL
=
45
ppm
in
males
LOAEL
=
125
ppm
in
males
based
on
plasma
ChEI
870.4200
Carcinogenicity
in
mice
42786901
(1993)
Acceptable/
guideline
0,
100,
1000
or
8000
ppm
(M:
0,
14.73,
145.99,
1248.93
mg/
kg/
day;
F:
0,
18.11,
180.86,
1440.62)
systemic
LOAEL
=
1000
ppm
based
on
increased
intracytoplasmic
droplets
in
bladder
in
males
and
females,
chronic
progressive
nephropathy
in
males;
NOAEL
=
100
ppm
RBC
ChEI
LOAEL
for
males
=
1000
ppm
,
for
females
=
8000
ppm;
NOAEL
=
100
ppm
for
males,
1000
ppm
for
females
plasma
ChEI
for
males
and
females
LOAEL
>
8000
ppm;
NOAEL
$
8000
ppm
brain
ChEI
for
males
and
females
LOAEL
=
8000
ppm;
NOAEL
=
1000
ppm
increase
in
vascular
tumors
in
all
treated
males
and
in
females
at
8000
ppm
increase
in
adenomas,
multiple
adenomas,
carcinomas
of
kidney
in
males
at
8000
ppm
increase
in
hepatic
neoplasms
(adenomas,
carcinomas,
one
hepatoblastoma)
in
females
at
8000
ppm
Appendix
1/
Table
1:
Toxicology
Profile
of
Carbaryl
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
870.4300
Chronic
Toxicity/
Carcinogenicity
in
rats
42918801
(1993)
Acceptable/
guideline
0,
250,
1500
&
7500
ppm
(M:
0,
10,
60.2,
349.5
mg/
kg/
day;
F:
0,
12.6,
78.6,
484.6
mg/
kg/
day)
systemic
LOAEL
=
1500
ppm
in
females
based
on
decreased
BW
and
BWG;
7500
ppm
in
males
based
on
increased
clinical
signs,
decreased
BW,
BWG
and
food
consumption,
increase
in
cataracts,
clinical
pathology
changes,
organ
weight
changes,
nonneoplastic
changes;
NOAEL
=
250
ppm
in
females
and
1500
ppm
in
males
plasma
ChEI
LOAEL
=
7500
ppm
in
males
and
females;
NOAEL
=
1500
ppm
RBC
ChEI
LOAEL
=
1500
ppm
in
males
and
females;
NOEL
=
250
ppm
brain
ChEI
LOAEL
=
7500
ppm
in
males
and
females;
NOEL
=
1500
ppm
at
7500
ppm,
increase
in
liver
adenomas
in
females,
increase
in
benign
transitional
cell
papillomas
and
transitional
cell
carcinomas
in
males
and
females,
transitional
cell
carcinoma
in
kidney
of
one
male,
increase
in
benign
thyroid
follicular
cell
adenomas
in
males,
follicular
cell
carcinoma
in
one
male
Bacterial
reverse
mutation
test
870.5100
41370303
(1989)
Acceptable/
guideline
5
1000
ug/
plate
No
evidence
of
mutagenicity
in
strains
TA1535,
TA
1537,
TA1538,
TA98
and
TA100
with
and
without
metabolic
activation
In
vitro
mammalian
chromosome
aberration
test
(Chinese
hamster
ovary
cells)
870.5385
41370304
(1989)
Acceptable/
guideline
without
S9
activation:
5
100
ug/
mL,
harvest
at
20
hrs.;
with
S9
activation:
25
300
ug/
mL,
harvest
at
30
hrs
Increase
in
chromosome
aberrations
with
S9
activation
In
vitro
mammalian
chromosome
aberration
test
870.5385
41370302;
41420201
(1989)
Unacceptable/
guideline
S9
activation:
1
300
ug/
mL
in
3
trials;
without
S9
activation:
1
300
ug/
mL
in
2
trials
Results
provide
no
clear
indication
of
a
mutagenic
response,
however
study
had
several
deficiencies
Mammalian
erythrocyte
micronucleus
test
870.
5395
44069301
(1996)
Unacceptable/
guideline
single
oral
gavage
dose
of
50,
100,
200
mg/
kg
Carbaryl
did
not
induce
a
clastogenic
or
aneugenic
effect,
however
there
was
no
convincing
evidence
that
MTD
was
achieved
Unscheduled
DNA
synthesis
870.5550
41370301;
41810601
(1989)
Acceptable/
guideline
0.5
25.0
ug/
mL
Negative
870.6200a
Acute
neurotoxicity
screening
battery
in
rats
MRID:
43845201
43845204
(1995)
Acceptable/
guideline
0,
10,
50,
125
mg/
kg
(oral
gavage)
Separate
study
for
ChEI:
0,
10,
30,
50
mg/
kg;
ChEI
done
1,
8,
24,
48
hrs
postdosing
Systemic
LOAEL
=
10
mg/
kg
based
on
decreased
RBC,
plasma,
blood,
brain
ChEI;
NOAEL
<
10
mg/
kg
Appendix
1/
Table
1:
Toxicology
Profile
of
Carbaryl
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
870.6200b
Subchronic
neurotoxicity
screening
battery
in
rats
MRID:
44122601
(1996)
Acceptable/
guideline
0,
1,
10,
30
mg/
kg/
day
(oral
gavage)
LOAEL
for
neurotoxicity
=
10
mg/
kg/
day
based
on
increased
FOB
changes;
NOAEL
=
1
mg/
kg/
day
LOAEL
for
ChEI
=
10
mg/
kg/
day
based
on
decreased
plasma,
blood,
RBC,
brain
ChEI;
NOAEL
=
1
mg/
kg/
day
870.6300
Developmental
neurotoxicity
in
rats
44393701
(1997)
Acceptable/
guideline
0,
0.1,
1.0,
10
mg/
kg
(oral
gavage)
Maternal
NOAEL
=
1.0
mg/
kg/
day
LOAEL
=
10
mg/
kg/
day
based
on
decreased
BWG;
FOB
changes;
RBC,
plasma,
whole
blood,
brain
ChEI
Offspring
tentative
NOAEL
=
1.0
mg/
kg/
day
tentative
LOAEL
=
10
mg/
kg/
day
based
on
alterations
in
morphometric
measurements
(measurements
were
not
done
at
lower
doses)
870.7485
Metabolism
and
pharmacokinetics
in
rats
43332101
(1994)
Acceptable/
guideline
1
mg/
kg
(single
and
repeated
oral
doses;
intravenous
dose)
and
50
mg/
kg
(single
oral
dose)
Absorption
was
complete
at
all
doses.
At
168
hrs.,
post
dose,
negligible
percentages
of
dose
in
any
tissues.
Kidney
and
blood
contained
highest
concentrations
of
radioactivity.
Excretion
mostly
through
urine.
A
metabolic
scheme
with
conjugated
and
non
conjugated
metabolites
was
proposed.
870.7485
Metabolism
and
pharmacokinetics
in
rats
44402501
(1997)
Acceptable/
nonguideline
50
mg/
kg
(single
oral
radiolabeled
dose);
daily
oral
radiolabeled
dose
of
2
mg/
kg
for
7
days
followed
by
83
daily
unlabeled
doses
of
0,
250,
1500
or
7500
ppm;
males
only
In
all
dosing
regimens,
urinary
and
fecal
excretion
was
93
103%
of
administered
dose
and
tissue
levels
of
radioactivity
were
minimal
at
168
hrs.
post
dosing.
Two
major
metabolites
in
tissues
at
6
hrs.
post
dosing
were
naphthyl
sulfate
and
naphthyl
glucuronide,
however
quantitation
was
not
possible.
A
total
of
23
and
20
components
were
identified
in
the
urine
and
feces,
respectively.
The
sulfate
conjugation
pathway
appears
to
be
saturable
following
a
83
day
feeding
at
7500
ppm.
BW
and
food
consumption
were
decreased
at
7500
ppm.
Increases
in
kidney,
spleen
and
thyroid
weights
were
observed
at
1500
and
7500
ppm.
Non
neoplastic
changes
in
liver,
thyroids
and
kidneys
were
observed
at
7500
ppm.
870.7600
Dermal
penetration
in
rats
43552901
(1995)
43.9%
a.
i.
Acceptable
35.6,
403,
3450
ug/
cm
2
%
absorbed
at
10
hrs.:
12.7,
7.44
and
1.93
at
35.6,
403
and
3450
ug/
cm
2
,
respectively
870.7600
Dermal
penetration
in
rats
43339701
(1994)
80.1%
a.
i.
Acceptable
63,
626,
3410
ug/
cm
2
%
absorbed
at
10
hrs:
8.90,
0.62
and
0.48
at
63,
626
and
3410
ug/
cm
2
,
respectively
Special
studies
in
mice
43282201
(1994)
Acceptable/
nonguideline
male
mice:
single
radiolabeled
dose
of
75
mg/
kg;
pretreatment
with
8000
ppm
unlabeled
carbaryl
for
2
wks.,
then
single
radiolabeled
dose
of
75
mg/
kg
Negative
for
DNA
binding
in
liver
Appendix
1/
Table
1:
Toxicology
Profile
of
Carbaryl
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
Special
studies
in
mice
43832601
(1994)
Acceptable/
nonguideline
continuation
of
MRID
43282201
in
liver
from
mice
treated
at
8000
ppm,
increase
in
microsomal
protein,
cytochrome
P450,
ethoxyresorufin
O
deethylase,
pentoxyresorufin
O
depentylase,
and
testosterone
hydrolases
indicates
phenobarbital
type
of
induction
of
metabolizing
enzymes
Special
study
in
mice
45281801,
45281802,
45236603
(1998
1999)
Acceptable/
nonguideline
0,
10,
30,
100,
300,
1000
and
4000
ppm
(0,
1.8,
5.2,
17.5,
51.2,
164.5
and
716.6
mg/
kg/
day)
There
was
no
evidence
of
neoplastic
or
preneoplastic
changes
in
vascular
tissue
in
heterozygous
p53
deficient
male
mice
treated
with
carbaryl
for
six
months.
N/
A
Not
Available
APPENDIX
2:
Incident
Review
Conclusions/
Recommendations
Based
on
Incident
Review
Data
on
incidents
of
adverse
reactions
in
humans
exposed
to
carbaryl
were
evaluated
from
several
sources,
including
OPP's
Incident
Data
System,
Poison
Control
Centers,
California
Department
of
Pesticide
Regulation,
National
Pesticide
Telecommunications
Network
and
the
open
literature.
The
data
from
the
Incident
Data
System
indicated
that
a
majority
of
cases
from
carbaryl
exposure
involved
dermal
reactions.
A
number
of
cases
involved
asthmatics
and
people
who
experienced
hives
and
other
allergic
type
reactions.
According
to
California
data,
about
half
of
the
cases
involved
skin
and
eye
effects
in
handlers.
About
a
quarter
of
the
skin
reactions
were
due
to
workers
that
were
exposed
to
residues
on
crops.
Reports
from
the
literature
are
very
limited
but
tend
to
support
the
finding
that
carbaryl
has
irritant
properties.
The
Poison
Control
Center
cases
involving
non
occupational
adults
and
older
children
showed
an
increased
risk
in
five
of
the
six
measures
reported.
These
cases
were
almost
twice
as
likely
to
require
serious
health
care
(hospitalization
or
treatment
in
a
critical
care
unit)
and
were
two
and
a
half
times
more
likely
to
experience
major
medical
outcome
lifethreatening
effects
or
significant
residual
disability)
as
compared
to
other
pesticides.
This
pattern
of
increased
risk
was
not
seen
among
occupational
reports
or
in
young
children.
This
may
mean
careless
handling
by
non
professionals
is
a
particular
hazard.
Five
case
reports
suggested
that
carbaryl
may
be
a
cause
of
chronic
neurological
or
psychological
problems.
Some
of
these
effects
appear
to
be
consistent
with
those
reported
from
organophosphate
poisoning.
However,
unlike
organophosphates,
no
controlled
studies
have
been
undertaken.
If
such
effects
occur
as
a
result
of
over
exposure
to
carbaryl,
they
appear
to
be
relatively
rare.
The
effects
reported
among
the
five
case
reports
are
too
inconsistent
to
draw
any
conclusions,
but
do
suggest
the
need
for
further
study.
Carbaryl
appears
capable
of
causing
dermal
and
allergic
type
reactions.
Data
support
the
need
for
personal
protective
equipment
and
eye
protection
for
handlers
for
field
workers
who
may
have
extensive
exposure
to
carbaryl.
Labels
for
products
should
advise
that
carbaryl
can
cause
sensitizing
effects
in
some
people.
Based
on
an
evaluation
of
limited
incident
data
on
domestic
animals
in
IDS,
it
is
recommended
that
all
labels
for
carbaryl
products
used
on
cats
contain
the
age
restriction
stated
in
PR
Notice
96
6
(should
not
be
used
in
kittens
less
than
12
weeks
of
age).
A
detailed
discussion
of
the
incident
data
is
presented
below.
Human
Incident
Data
Review
A
review
of
the
human
incident
data
on
carbaryl
was
prepared
by
Dr.
Jerome
Blondell
and
Ms.
Monica
Spann
(D267127
dated
July
17,
2000).
The
following
data
bases
were
consulted
for
the
poisoning
incident
data
on
the
active
ingredient
Carbaryl
(PC
Code:
056801):
1)
OPP
Incident
Data
System
(IDS)
reports
of
incidents
from
various
sources,
including
registrants,
other
federal
and
state
health
and
environmental
agencies
and
individual
consumers,
submitted
to
OPP
since
1992.
2)
Poison
Control
Centers
as
the
result
of
a
data
purchase
by
EPA,
OPP
received
Poison
Control
Center
data
covering
the
years
1993
through
1998
for
all
pesticides.
Most
of
the
national
Poison
Control
Centers
(PCCs)
participate
in
a
national
data
collection
system,
the
Toxic
Exposure
Surveillance
System
which
obtains
data
from
about
65
70
centers
at
hospitals
and
universities.
3)
California
Department
of
Pesticide
Regulation
California
has
collected
uniform
data
on
suspected
pesticide
poisonings
since
1982.
Physicians
are
required,
by
statute,
to
report
to
their
local
health
officer
all
occurrences
of
illness
suspected
of
being
related
to
exposure
to
pesticides.
4)
National
Pesticide
Telecommunications
Network
(NPTN)
NPTN
is
a
toll
free
information
service
supported
by
OPP.
A
ranking
of
the
top
200
active
ingredients
for
which
telephone
calls
were
received
during
calendar
years
1984
1991
and
1995
1999
has
been
prepared
for
the
categories
human
incidents,
animal
incidents,
calls
for
information,
and
others.
Incident
Data
System
There
were
approximately
500
reports
in
IDS
concerning
exposure
of
humans
to
carbaryl.
At
least
380
cases
were
considered
minor
(minimal
symptoms
with
no
residual
disability)
and
were
not
included
in
the
review.
The
most
frequently
reported
symptoms
were
of
a
dermatological
nature,
either
dermal
irritation
or
possibly
a
dermal
manifestation
of
an
allergic
response
(e.
g.,
hives,
welts,
rash,
etc.).
Clinical
signs
or
symptoms
less
frequently
reported
were
nausea,
vomiting,
diarrhea,
respiratory
irritation
and
difficulty
breathing.
Most
of
the
incidents
were
associated
with
dermal
exposure;
however,
a
few
resulted
after
inhalation
of
the
product.
There
was
one
report
of
an
attempted
suicide.
In
1993,
a
21
year
old
man
ingested
about
75
ml
of
Beetle
Bait
(21.3%
carbaryl,
Registration
Number
869
134).
No
information
on
the
symptoms
or
outcome
of
the
case
were
provided.
There
was
also
one
death.
In
1996,
a
woman
with
a
history
of
chronic
asthma
experienced
shock
and
severe
respiratory
distress
after
she
used
Mycodex
Pet
Shampoo
(0.5%
carbaryl,
Registration
Number
2097
8)
on
her
dog.
She
was
hospitalized
but
went
into
a
coma
and
died
five
days
later
(IDS
3694
1).
Poison
Control
Center
(PCC)
Data
1993
through
1998
The
PCC
data
base
for
1993
through
1998
contained
174
cases
involving
occupational
exposures
in
adults
and
older
children
(outcome
determined
in
90
cases),
3033
nonoccupational
exposures
in
adults
and
older
children
(outcome
determined
in
1351
cases)
and
2147
exposures
in
children
under
the
age
of
six
(outcome
determined
in
1248
cases).
Cases
involving
exposures
to
multiple
products
were
excluded.
The
data
from
cases
in
which
the
outcome
was
determined
were
compared
to
all
other
pesticides
using
six
measures:
percent
with
symptoms,
percent
with
moderate
or
more
severe
outcome,
percent
with
life
threatening
or
fatal
outcome,
percent
of
exposed
cases
seen
in
a
health
care
facility,
percent
hospitalized
and
percent
seen
in
an
intensive
care
facility.
For
occupational
cases,
carbaryl
appears
to
be
somewhat
less
hazardous
than
all
pesticides
combined,
as
determined
by
five
of
the
six
measures
reported.
Cases
involving
non
occupational
adults
and
older
children
showed
an
increased
risk
in
five
of
the
six
measures
reported.
In
particular
these
non
occupational
cases
were
nearly
twice
as
likely
to
require
serious
health
care
(hospitalization
or
treatment
in
a
critical
care
unit)
and
were
2.5
times
more
likely
to
experience
major
medical
outcome
(life
threatening
effects
or
significant
residual
disability).
These
data
suggest
that
some
consumers
are
using
this
chemical
in
a
careless
manner.
For
cases
involving
children
under
six
years
of
age,
carbaryl
has
a
similar
hazard
profile
to
all
other
pesticides.
California
Data
1982
through
1996
Detailed
descriptions
of
226
cases
submitted
to
the
California
Pesticide
Illness
Surveillance
Program
(1982
1996)
were
reviewed.
In
90
of
these
cases,
carbaryl
was
used
alone
or
was
judged
to
be
responsible
for
the
health
effects.
Only
cases
with
a
definite,
probable
or
possible
relationship
were
reviewed.
Carbaryl
ranked
37
th
as
a
cause
of
systemic
poisoning
in
California.
The
number
of
reports
from
California
declined
by
over
half
from
the
first
five
years
of
the
reporting
period
(1982
1986)
to
the
last
five
years
(1992
1996).
It
is
difficult
to
determine
whether
some
of
this
decline
might
be
related
to
a
decrease
in
usage
because
the
method
of
collecting
use
information
changed
after
1989.
Of
the
90
persons
reported
to
have
illnesses,
a
total
of
43
(48%)
had
systemic
illnesses,
20
(22%)
had
eye
irritation,
21
(23%)
had
skin
irritation,
1(
1%)
had
respiratory
illness
and
5
(6%)
had
a
combination
of
effects.
A
total
of
26
workers
were
disabled
(took
time
off
work,
1
for
more
than
10
days)
as
the
result
of
carbaryl
exposure.
Seven
required
hospitalization
(1
5
days).
Applicators
were
associated
with
the
majority
of
the
exposures.
Clinical
signs/
symptoms
in
these
workers
included
nausea,
vomiting,
skin
rashes,
sore
throat,
lip
swelling,
chemical
conjunctivitis,
dizziness,
eye
irritation,
contact
dermatitis,
blurry
vision,
chest
pains,
and
several
other
symptoms.
National
Pesticide
Telecommunications
Network
On
the
list
of
the
top
200
chemicals
for
which
NPTN
received
calls
from
1984
1991
inclusively,
carbaryl
was
ranked
5
th
with
503
incidents
in
humans
reported
and
85
incidents
in
animals
(mostly
pets).
For
the
years
1995
through
1998,
carbaryl's
rank
ranged
from
7
th
to
12
th
with
110
incidents
in
humans
reported
and
26
incidents
in
animals.
Most
of
the
decline
in
reported
human
cases
from
the
earlier
time
period
is
due
to
the
reduced
level
of
incident
reporting
overall.
However,
even
taking
this
into
account,
there
does
appear
to
be
some
reduction
in
carbaryl
incidents
which
is
also
reflected
in
the
lower
rankings
reported
for
the
later
years
(1995
1998).
Literature
Summary
Thirteen
epidemiological
studies/
case
reports
from
the
open
literature
were
reviewed.
Five
case
reports
suggested
that
carbaryl
may
cause
long
term
neurological
or
12
Branch
RA,
Jacqz
E
(1986).
Is
carbaryl
as
safe
as
its
reputation?
Does
it
have
a
potential
for
causing
chronic
neurotoxicity
in
humans?.
The
American
Journal
of
Medicine
80(
4):
659
664.
13
Brewer
B
(2000).
A
rare
cause
of
acute
confusional
state
(Letter
to
the
Editor).
Journal
of
Accidental
Emergency
Medicine
17(
1):
77.
14
Devinsky
O,
Kernan
J,
Bear
DM
(1992).
Aggressive
behavior
following
exposure
to
cholinesterase
inhibitors.
Journal
of
Neuropsychiatry
4(
2):
189
194.
15
Dickoff
DJ,
Gerber
O,
Turovsky
Z
(1987).
Delayed
neurotoxicity
after
ingestion
of
carbamate
pesticide.
Neurology
37(
7):
1229
1231.
16
Wiener
PK,
Young
RC
(1995).
Late
onset
psychotic
depression
associated
with
carbaryl
exposure.
American
Journal
of
Psychiatry152(
4):
646
647.
17
Savitz
DA,
Arbuckle
T,
Kaczor
D,
Curtis
KM.
(1997).
Male
pesticide
exposure
and
pregnancy
outcome.
American
Journal
of
Epidemiology
146(
12):
1025
1036.
18
Whorton
DM,
Avashia
BH,
Hull
EQ.
(1979).
Testicular
function
among
carbaryl
exposed
employees.
Journal
of
Toxicology
and
Environmental
Health
5:
929
941.
19
Wyrobek
AJ,
Watchmaker
G,
Gordon
L,
Wong
K,
Moore
D
2d,
Whorton
D
(1981).
Sperm
shape
abnormalities
in
carbaryl
exposed
employees.
Environmental
Health
Perspectives
40:
255
265.
psychologicalproblems.
12,13,14,15,16
Two
of
these
cases
involved
attempted
suicides
in
which
large
doses
of
carbaryl
containing
products
were
ingested.
Some
of
the
effects
from
carbaryl
exposure
are
consistent
with
those
reported
from
organophosphate
poisoning.
However,
no
controlled
studies
have
been
conducted.
If
such
effects
occur
as
a
result
of
carbaryl
overexposure
they
appear
to
be
relatively
rare.
The
effects
observed
in
the
case
reports
are
too
inconsistent
to
draw
any
conclusions,
but
do
suggest
the
need
for
further
study.
Other
literature
articles
concerned
epidemiology
studies
to
evaluate
the
effects
of
pesticides
on
reproduction.
In
the
1979
Ontario
Farm
Family
Study
by
Savitz
et
al
17
,
the
effects
of
activities
and
specific
pesticides
on
male
farmer's
fertility
were
considered.
The
results
suggested
that
thiocarbamates,
carbaryl
and
other
pesticides
were
most
strongly
associated
with
miscarriage.
The
adjusted
odds
ratio
for
carbaryl
used
on
crops
was
2.1
with
a
95
percent
confidence
interval
of
1.1
to
4.1
(borderline
significance).
Use
of
carbaryl
in
the
yard
was
not
associated
with
a
significantly
increased
risk
of
miscarriage
and
carbaryl
was
not
a
significant
risk
factor
for
preterm
delivery
or
small
for
gestational
age
births.
In
a
1979
study
of
male
workers
who
produced
and
packaged
carbaryl,
Whorton
et
al
18
concluded
that
there
was
no
evidence
of
sperm
count
suppression
resulting
from
exposure
to
the
chemical.
Whorton
et
al.
(1979)
and
Wyrobek
et
al
19
(1981)
used
the
same
cohort
in
their
studies
to
determine
the
effects
on
fertility
by
checking
for
infertile
marriages
and
by
measuring
sperm
counts
and
serum
gonadotropins.
The
carbaryl
exposed
group
included
nearly
three
times
as
many
oligospermic
men
as
the
control
group.
Wyrobek
et
al.
(1981)
concluded
there
was
a
non
dose
related,
significant
elevation
in
sperm
head
abnormalities
compared
to
controls,
that
may
not
be
reversible.
Both
of
the
studies
had
low
participation
rates,
relied
on
self
reporting
of
exposure
levels,
and
used
less
than
ideal
control
groups.
20
Senthilselvan
A,
McDuffie
HH,
Dosman
JA.
1992.
Association
of
asthma
with
use
of
pesticides.
Results
of
a
cross
sectional
survey
of
farmers.
Am
Rev
Respir
Dis
146(
4):
884
887.
21
Sharma
VK,
Kaur
S.
1990.
Contact
sensitization
by
pesticides
in
farmers.
Contact
Dermatitis
23:
77
80.
There
were
also
two
studies
assessing
carbaryl's
potential
to
induce
an
allergic
reaction.
Senthilselvan
et
al.
(1992)
20
reported
on
the
association
between
self
reported
asthma
and
pesticide
use
in
1,939
farmers.
The
prevalence
of
asthma
was
significantly
associated
with
the
use
of
carbamate
insecticides
regardless
of
age,
smoking
pack
years,
and
nasal
allergic
reactions.
The
authors
concluded
that
the
possibility
of
exposure
to
agriculture
chemicals
could
be
related
to
lung
dysfunction
in
exposed
farmers.
Sharma
and
Kaur
(1990)
21
reported
on
30
farmers
that
had
contact
dermatitis
after
using
pesticides
for
several
years.
The
farmers
included
25
males
and
5
females,
between
the
ages
of
28
and
70
years
old.
Patch
testing
was
conducted
on
the
upper
back
and
readings
were
taken
on
the
second,
third,
and
seventh
day.
Allergic
reactions
to
one
or
more
pesticides
were
seen
in
11
patients.
One
patient
was
sensitive
to
carbaryl
and
two
patients
to
3
each
(2,4
D,
thiram,
carbaryl;
pendimethalin,
methyl
parathion
and
carbofuran).
Carbamates,
including
carbaryl,
were
the
most
frequent
sensitizers.
Allergic
reactions
did
not
occur
in
the
twenty
controls
included
in
the
study.
Unpublished
Epidemiology
Study
Rhone
Poulenc
submitted
an
epidemiologic
study
of
plant
workers
exposed
to
carbaryl
titled
"Standardized
Mortality
Ratio
Analysis
of
Employees
Exposed
to
Carbaryl
at
the
RhonePoulenc
Institute,
West
Virginia
Plant",
which
was
reviewed
by
Dr.
Jerome
Blondell
(DP
Barcode
D194815).
The
results
were
part
of
a
ten
year
vital
status
update
undertaken
by
the
National
Institute
of
Occupational
Safety
and
Health.
The
study
included
all
individuals
who
were
first
hired
between
1960
(when
the
production
of
carbaryl
started)
and
through
1978.
The
vital
status
of
all
workers
was
determined
through
1988
using
the
National
Death
Index.
A
total
of
522
employees
were
identified
as
belonging
to
either
the
production,
packing/
distribution,
or
maintenance
facilities.
Follow
up
through
1988
showed
25
deaths,
including
nine
due
to
cancer.
Significantly
less
deaths
(50%)
were
seen
compared
to
the
number
expected.
No
category
of
death
resulted
in
a
statistically
significant
excess.
Those
categories
that
exhibited
an
excess
(greater
than
the
number
of
expected
cases)
were
usually
based
on
a
single
reported
death
with
very
wide
confidence
intervals.
For
brain
cancer,
there
were
two
deaths
(0.5
expected),
but
they
had
different
histologic
origin
which
reduces
the
likelihood
that
they
were
due
to
the
same
exposure.
HED
concluded
that
the
epidemiologic
study
does
not
add
significant
new
information
concerning
adverse
health
effects
of
carbaryl.
The
sample
of
workers
was
too
small
and
the
period
of
follow
up
to
too
short
to
permit
definitive
conclusions.
Domestic
Animal
Incident
Review
The
domestic
animal
incident
review
was
prepared
by
Dr.
Virginia
Dobozy
(D266621
dated
June
12,
2000).
There
are
approximately
69
active
products
containing
carbaryl
with
use
sites
for
dogs
and
cats
in
OPP's
Reference
File
System
(REFS).
The
majority
of
the
products
are
5
10%
lawn
and
garden
dusts,
which
may
be
registered
for
use
on
animal
bedding
and
thus
are
included
in
the
REFS
search.
Most
of
the
powders
for
intentional
application
to
dogs
and
cats
for
flea
and
tick
control
also
contain
5
10%
carbaryl,
some
in
combination
with
pyrethrins
and
synergists.
However,
two
products
contain
12.5%
carbaryl
in
combination
with
pyrethrins.
Three
products
contain
carbaryl
(10
12.5%)
in
combination
with
0.25%
methoxylchlor.
There
is
one
shampoo
which
contains
0.5%
carbaryl,
two
flea
collars
with
either
9.5%
(cats)
or
17%
(dogs)
carbaryl
and
a
dip
for
dogs
with
60%
carbaryl.
In
general,
the
use
of
powders,
dips
and
sprays
for
flea
and
tick
control
in
dogs
and
cats
has
been
replaced
within
the
last
five
years
with
oral
(FDA
regulated)
or
spot
on
formulations.
As
there
are
no
spot
on
carbaryl
preparations,
it
can
be
assumed
that
the
use
of
this
chemical
for
flea
and
tick
control
has
declined.
There
are
213
reports
in
IDS
for
carbaryl
for
domestic
animals
from
1991
to
May,
2000.
Only
those
incidents
from
1998
(most
recent
year
with
complete
data)
were
reviewed
in
order
to
provide
an
evaluation
of
current
adverse
reports
in
domestic
animals.
In
1998,
there
were
35
incidents
in
IDS
involving
23
dogs,
9
cats
and
1
pig.
One
incident
involved
two
dogs
and
in
three
incidents,
the
species
was
not
identified.
Only
two
incidents
involved
products
registered
for
use
on
dogs
and
cats.
In
one,
an
8
week
old
kitten
treated
with
Zodiac
Flea
and
Tick
Powder
for
Dogs
developed
vomiting
and
anorexia
and
died
the
next
day.
In
the
other,
a
dog
was
reported
to
have
had
a
reaction
to
a
shampoo
with
carbaryl;
no
other
data
were
provided.
The
majority
of
the
remaining
incidents
involved
products
containing
a
5%
carbaryl
dust
or
a
molluscicide
which
contains
2%
metaldehyde
and
5%
carbaryl.
A
wide
variety
of
clinical
signs
were
reported.
Most
of
the
incidents
were
evaluated
and
classified
as
to
causality
(doubtful,
low,
moderate
or
high
suspicion)
by
the
ASPCA/
National
Animal
Poison
Control
Center.
All
were
classified
as
doubtful
or
low
suspicion.
A
summary
review
of
incidents
for
a
5%
carbaryl
powder
from
one
registrant,
along
with
the
one
report
from
1998,
provided
some
evidence
that
young
kittens
(<
12
weeks)
may
be
susceptible
to
adverse
reactions
to
carbaryl.
It
is
recommended
that
all
labels
for
carbaryl
products
used
on
cats
contain
the
age
restriction
stated
in
PR
Notice
96
6
(should
not
be
used
in
kittens
less
than
12
weeks
of
age).
| epa | 2024-06-07T20:31:42.114605 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0004/content.txt"
} |
EPA-HQ-OPP-2002-0138-0005 | Supporting & Related Material | "2002-07-31T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
May
29,
2002
Memorandum
SUBJECT:
Carbaryl:
Occupational
and
Residential
Exposure
Assessment
and
Recommendations
for
the
Reregistration
Eligibility
Decision
Document.
PC
Code
056801;
Submission
No.
S533427
;DP
Barcode:
D281418.
FROM:
Jeffrey
L.
Dawson,
Chemist/
Risk
Assessor
Reregistration
Branch
1
Health
Effects
Division
(7509C)
THROUGH:
Whang
Phang,
PhD,
Senior
Scientist
Reregistration
Branch
1
Health
Effects
Division
(7509C)
TO:
Anthony
Britten,
Chemical
Review
Manager
Reregistration
Branch
Special
Review
and
Registration
Division
Reviewers:
Science
Advisory
Committee
on
Exposure;
Alan
Nielsen.
Risk
Assessment
Review
Committee
(June
6,
2001
Report)
This
document
presents
updated
occupational
and
residential
exposures/
risks
which
have
been
calculated
due
to
recent
changes
in
the
hazard
assessment
for
carbaryl
(April
25,
2002
HIARC
Meeting)
and
changes
in
the
FQPA
safety
factor
from
10
to
1
based
on
recent
policy
changes
(April
3,
2002
FQPA
SFC
Report).
Several
modifications
to
the
exposure
assessment
have
also
been
incorporated
due
to
recent
changes
in
Exposure
SAC
Policy
(e.
g.,
how
risks
from
pet
use
products
are
calculated,
the
use
of
ARTF
data
from
greenhouses,
and
mosquito
control
applications),
the
submission
of
a
Sevin
XLR
Label
for
mosquito
control,
and
changes
in
the
short
term/
intermediateterm
exposure
duration
interface
from
7
days
to
30
days.
Also
included
in
this
document
is
a
sitespecific
assessment
of
risks
associated
with
a
Section
24C
(SLN
WA
900013)
where
carbaryl
is
intended
to
control
Ghost
and
Mud
Shrimp
in
oyster
beds.
Table
of
Contents
Executive
Summary..............................................................
4
1.0
Occupational
and
Residential
Exposure/
Risk
Assessment
.........................
12
1.1
Purpose
..............................................................
12
1.2
Criteria
for
Conducting
Exposure
Assessments
..............................
12
1.3
Summary
of
Hazard
Concerns
.........................................
12
1.
4
Incident
Reports....................................................
14
1.
5
Summary
of
Use
Patterns
and
Formulations
..............................
14
1.5.1
End
Use
Products
............................................
15
1.5.2
Mode
of
Action
and
Targets
Controlled
...........................
17
1.5.3
Registered
Use
Categories
and
Sites
.............................
18
1.5.4
Application
Parameters
.......................................
22
2.0
Occupational
Exposures
and
Risks
..........................................
25
2.1
Occupational
Handler
Exposures
and
Risks
.................................
25
2.1.1
Handler
Exposure
Scenarios
....................................
26
2.1.2
Data
and
Assumptions
For
Handler
Exposure
Scenarios
..............
30
2.1.3
Occupational
Handler
Exposure
and
Non
Cancer
Risk
Estimates
.......
45
2.1.4
Occupational
Handler
Exposure
and
Risk
Estimates
for
Cancer.
........
56
2.1.5
Summary
of
Risk
Concerns
and
Data
Gaps
for
Handlers
..............
62
2.1.6
Recommendations
For
Refining
Occupational
Handler
Risk
Assessment
.
63
2.2
Occupational
Postapplication
Exposures
and
Risks
........................
63
2.2.1
Occupational
Postapplication
Exposure
Scenarios
...................
63
2.2.2
Data
and
Assumptions
for
Occupational
Postapplication
Exposure
Scenarios
...........................................................
69
2.2.3
Occupational
Postapplication
Exposure
and
Noncancer
Risk
Estimates
.
.
77
2.2.4
Occupational
Postapplication
Exposure
and
Risk
Estimates
for
Cancer
...........................................................
86
2.2.5
Summary
of
Occupational
Postapplication
Risk
Concerns
and
Data
Gaps
...........................................................
92
2.2.6
Recommendations
For
Refining
Occupational
Postapplication
Risk
Assessment..................................................
93
2.
3
Occupational
Risk
Characterization
....................................
93
2.3.1
Handler
Characterization
.......................................
93
2.3.2
Postapplication
Characterization
.................................
95
3.0
Residential
and
Other
Non
Occupational
Exposures
and
Risks
.....................
97
3.1
Residential
Handler
Exposures
and
Risks
................................
97
3.1.1
Handler
Exposure
Scenarios
....................................
98
3.1.2
Data
and
Assumptions
For
Handler
Exposure
Scenarios
..............
99
3.1.3
Residential
Handler
Exposure
and
Non
Cancer
Risk
Estimates
........
108
3.1.4
Residential
Handler
Exposure
and
Risk
Estimates
for
Cancer
.........
113
3.1.5
Summary
of
Risk
Concerns
and
Data
Gaps
for
Handlers
.............
117
3.1.6
Recommendations
For
Refining
Residential
Handler
Risk
Assessment
.
.
117
3.2
Residential
Postapplication
Exposures
and
Risks
.........................
117
3.2.1
Residential
Postapplication
Exposure
Scenarios
....................
118
3.2.2
Data
and
Assumptions
for
Residential
Postapplication
Exposure
Scenarios
..........................................................
123
3.2.3
Residential
Postapplication
Exposure
and
Noncancer
Risk
Estimates
.
.
.
129
3.2.4
Residential
Postapplication
Exposure
and
Risk
Estimates
for
Cancer
.
.
.
142
3.2.5
Summary
of
Residential
Postapplication
Risk
Concerns
and
Data
Gaps
.
144
3.2.6
Recommendations
For
Refining
Residential
Postapplication
Risk
Assessment
..........................................................
146
3.
3
Residential
Risk
Characterization
.....................................
146
3.3.1
Handler
Characterization
......................................
146
3.3.2
Postapplication
Characterization
................................
147
Appendix
A:
Use
Information
For
Carbaryl
Appendix
B:
Carbaryl
Occupational
Handler
Exposure
Data
Appendix
C:
Carbaryl
Occupational
Handler
Risk
Assessment
Appendix
D:
Carbaryl
Residue
Dissipation
(DFR
&
TTR)
Data
Appendix
E:
Carbaryl
Occupational
Postapplication
Risk
Assessment
Appendix
F:
Carbaryl
Residential
Handler
Exposure
Data
Appendix
G:
Carbaryl
Residential
Handler
Risk
Assessment
Appendix
H:
Carbaryl
Residential
Postapplication
Risk
Assessment
For
Turf
Uses
Appendix
I:
Carbaryl
Residential
Postapplication
Risk
Assessment
For
Garden/
Ornamental
Uses
Appendix
J:
Carbaryl
Residential
Postapplication
Risk
Assessment
For
Pet
Uses
Appendix
K:
Determination
of
Deposition
Factors
For
Carbaryl
Mosquito
Control
Uses
Appendix
L:
Carbaryl
Residential
Postapplication
Risk
Assessment
For
Mosquito
Control
Appendix
M:
Carbaryl
Residential
Postapplication
Risk
Assessment
For
Oyster
Bed
Uses
4
Executive
Summary
Carbaryl
[1
napthyl
methylcarbamate]
is
one
of
the
most
widely
used
broadspectrum
insecticides
in
agriculture,
professional
turf
management,
professional
ornamental
production,
and
in
the
residential
pet,
lawn
and
garden
markets.
Carbaryl
formulations
include
baits,
dusts,
pet
collars,
flowable
concentrates,
emulsifiable
concentrates,
granulars,
soluble
concentrates,
and
wettable
powders.
Carbaryl
is
used
in
agriculture
to
control
pests
on
terrestrial
food
crops
including
fruit
and
nut
trees
(e.
g.,
apples,
pears,
almonds,
walnuts,
and
citrus),
many
types
of
fruit
and
vegetables
(e.
g.,
cucumbers,
tomatoes,
lettuce,
blackberries,
and
grapes),
and
grain
crops
(e.
g.,
corn,
rice,
sorghum,
and
wheat).
Carbaryl
is
also
used
for
direct
animal
treatments
to
control
pests
on
poultry
and
companion
animals
such
as
dogs
and
cats.
There
are
other
uses
for
ornamentals
and
turf,
including
production
facilities
such
as
greenhouses,
golf
courses,
and
residential
sites
that
can
be
treated
by
professional
applicators
(e.
g.,
annuals,
perennials,
shrubs).
Carbaryl
can
also
be
used
by
homeowners
on
lawns,
for
home
and
garden
uses,
and
on
companion
animals.
There
are
no
labels
for
indoor
uses
such
as
crack
and
crevice
treatments
of
a
residence.
In
agriculture,
groundboom,
airblast,
and
aerial
applications
are
typical.
Other
applications
can
also
be
made
using
handheld
equipment
such
as
low
pressure
handwand
sprayers,
backpack
sprayers,
and
turfguns.
Homeowners
can
also
use
other
types
of
application
equipment
including
trigger
sprayers,
hose
end
sprayers,
and
ready
to
use
dust
packaging.
Carbaryl
also
has
more
specialized
uses
that
can
lead
to
exposures
in
the
general
population
which
were
considered
in
this
assessment
such
as
an
adulticide
for
mosquito
control
and
for
Ghost
and
Mud
shrimp
control
in
oyster
beds
in
Washington
State.
A
number
of
studies
were
considered
in
the
development
of
the
carbaryl
risk
assessment
that
include
scenario
and/
or
chemical
specific
handler
exposure
data
for
occupational
uses
and
also
for
residential
uses.
Chemical
specific
residue
dissipation
data
were
also
considered
for
agricultural
crops,
turf,
and
the
oyster
bed
uses.
The
occupational
handler
exposure
studies
that
were
used,
quantified:
exposure
to
pet
groomers
using
a
carbaryl
containing
shampoo;
exposure
during
application
of
a
granular
with
two
different
backpack
devices
and
spoons;
application
with
a
trigger
sprayer;
and
application
to
turf
with
high
volume/
low
pressure
handgun
for
liquid
sprays
and
a
granular
spreader.
There
are
no
data
compensation
issues
associated
with
any
of
these
data.
In
all
other
cases,
occupational
handler
exposure
was
addressed
using
PHED
(Pesticide
Handlers
Exposure
Database).
The
occupational
postapplication
assessment
was
completed
using
5
different
residue
dissipation
studies
on
4
crops
and
turf.
The
dislodgeable
foliar
residue
(DFR)
dissipation
studies
were
all
conducted
by
the
Agricultural
Reentry
Task
Force
(ARTF)
using
carbaryl
on
cabbage,
olives,
sunflowers,
and
tobacco.
Again,
there
are
no
data
compensation
issues
associated
with
the
DFR
data
because
Aventis
is
a
member
of
the
ARTF.
The
sunflower
and
tobacco
data
were
used
only
to
assess
risks
for
their
specific
crop
groups
because
of
aerial
application
with
the
sunflowers
and
due
to
various
features
of
the
tobacco
crop
(e.
g.,
leaf
type
and
shape).
The
olive
and
cabbage
data
were
generally
used
to
complete
the
assessments
for
all
tree
crops
and
all
other
crops,
respectively.
The
turf
transferable
residue
(TTR)
data
were
generated
by
the
Aventis
Corporation
at
sites
in
California,
Georgia,
and
Pennsylvania.
These
chemical
specific
dissipation
data
were
all
used
in
conjunction
with
the
Agency's
revised
policy
on
transfer
coefficients
to
calculate
postapplication
exposures
and
risks
(August
7,
2000/
Policy
003.1).
All
of
the
studies
used
by
the
5
Agency
to
assess
occupational
risks
were
considered
to
be
the
best
source
of
data
available
for
the
scenario
where
it
was
used.
These
recent
studies
are
all
considered
high
quality
based
on
current
Agency
guidance.
The
oyster
bed
uses
were
evaluated
using
sediment
and
water
concentration
data
generated
by
the
Washington
State
Department
of
Ecology
or
the
Shoalwater
Creek
Indian
Tribe.
A
number
of
other
studies
were
submitted
by
the
Aventis
Corporation
that
focused
on
quantifying
exposures
during
the
application
of
homeowner
products.
Three
studies
used
carbarylcontaining
products
to
quantify
exposures
during
application
of
a
dust
to
dogs,
application
of
various
products
to
gardens
(i.
e.,
dusts,
trigger
sprayer,
and
liquid
application
with
hose
end
sprayer
or
low
pressure
handwand),
and
application
of
a
liquid
to
trees
and
shrubs
using
a
hose
end
sprayer
or
low
pressure
handwand
sprayer.
In
addition
to
these
studies,
which
were
all
conducted
by
the
Aventis
Corporation,
an
additional
study
completed
by
the
ORETF
that
quantified
exposures
during
granular
application
to
turf
with
a
rotary
spreader
and
during
liquid
spray
application
to
turf
with
a
hose
end
sprayer
was
used.
Aventis
is
a
member
of
the
ORETF
so
there
are
no
data
compensation
issues
associated
with
the
use
of
this
study.
For
postapplication
exposures,
Aventis
also
submitted
a
study
which
quantified
dermal
exposure
on
turf
using
oxadiazon
(Ronstar
formulation).
The
Agency
did
not
use
this
study
in
the
risk
assessment
because
of
technical
issues
including
levels
of
transferability
compared
to
the
carbaryl
TTR
data
and
the
dormant
timing
of
the
application
which
is
not
typical
for
carbaryl.
In
cases
where
chemical
or
scenario
specific
data
were
unavailable,
the
Agency
relied
on
guidance
provided
in
the
SOPs
For
Residential
Exposure
Assessment
and
various
supporting
documents.
This
risk
assessment
incorporates
the
recent
revisions
by
the
HIARC
and
reconsideration
of
the
FQPA
safety
factor
based
on
recently
revised
policies.
Calculations
have
been
completed
for
short
term
and
intermediate
term
exposures
for
all
occupational
scenarios.
Chronic
exposures
have
also
been
calculated
for
a
limited
number
of
scenarios
in
the
ornamental/
greenhouse
industry
where
such
exposure
patterns
might
be
expected.
Risks
for
residential
handlers
are
considered
to
be
shortterm
in
nature
only
because
homeowner
uses
are
expected
to
be
infrequent.
Residential
postapplication
risks
have
been
calculated
based
on
short
term
and
intermediate
term
exposures
because
repeated
postapplication
exposures
are
likely
while
they
are
not
for
handlers
based
on
use
patterns.
Cancer
risks
were
calculated
for
all
adults
scenarios
using
a
linear,
low
dose
extrapolation
approach
(LADD
or
Lifetime
Average
Daily
Dose
and
Q1*).
The
short
and
intermediate
term
dermal
risk
assessments
for
carbaryl
were
based
on
a
21
day
dermal
toxicity
study
in
rats
that
used
technical
material
where
decreases
in
red
blood
cell
and
brain
cholinesterase
were
observed
(NOAEL
=
20
mg/
kg/
day).
The
short
term
inhalation
and
nondietary
ingestion
risk
assessments
for
carbaryl
were
based
on
a
developmental
neurotoxicity
study
in
rats
where
alterations
in
FOB
parameters
on
the
first
day
of
dosing
were
observed
(NOAEL
=
1
mg/
kg/
day).
The
results
of
this
study
were
applied
to
short
term
exposure
durations
of
up
to
30
days.
The
intermediate
term
inhalation
and
non
dietary
ingestion
risk
assessments
for
carbaryl
are
based
on
a
subchronic
neurotoxicity
study
in
(NOAEL
=
1
mg/
kg/
day).
The
effects
that
were
observed
and
selected
as
the
basis
for
the
endpoint
used
in
risk
assessment
included
decreases
in
plasma,
red
blood
cell,
whole
blood
and
brain
cholinesterase
activity
and
changes
in
functional
observational
battery
(FOB)
parameters.
The
results
of
this
study
were
applied
to
exposure
durations
greater
than
30
days
up
to
several
months.
The
chronic
risk
assessments
for
carbaryl
were
based
on
a
1
year
dog
feeding
study
6
(LOAEL
=
3.1
mg/
kg/
day).
The
effects
that
were
observed
and
selected
as
the
basis
for
the
endpoint
used
in
risk
assessment
included
decreases
in
plasma,
and
brain
cholinesterase
activity.
The
results
of
this
study
were
applied
to
chronic
exposure
durations
and
to
all
routes
of
exposure
(i.
e.,
dermal,
inhalation,
and
non
dietary
ingestion).
Carbaryl
was
classified
as
a
Class
C
carcinogen
and
was
assessed
for
carcinogenic
risk
from
exposure
using
a
linear,
low
dose
extrapolation
approach
with
a
Q1*
of
8.75
x
10
4
(mg/
kg/
day)
1
.
A
dermal
absorption
factor
of
12.7
percent
was
selected
from
a
rat
dermal
absorption
study
using
radiolabeled
14
C.
A
100
percent
inhalation
absorption
factor
was
used
to
convert
all
inhalation
exposures
to
an
oral
equivalent
inhalation
dose.
The
Agency's
level
of
concern
for
noncancer
risks
(i.
e.,
target
level
for
MOEs
or
Margins
of
Exposure)
is
defined
by
the
uncertainty
factors
that
are
applied
to
the
assessment.
The
Agency
applies
a
factor
of
100
in
cases
to
account
for
inter
species
extrapolation
to
humans
from
the
animal
test
species
and
to
account
for
intra
species
sensitivity.
In
cases
where
a
NOAEL
was
not
identified
and
a
LOAEL
was
used
for
risk
assessments,
an
additional
uncertainty
factor
of
3
was
applied
for
chronic
exposures.
Based
on
the
requirements
of
the
1996
Food
Quality
Protection
Act,
the
Agency
must
also
consider
sensitive
populations
in
its
non
occupational
risk
assessments.
The
Agency
reduced
the
FQPA
safety
factor
to
1x
for
non
occupational
exposures
to
carbaryl
because
there
are
no
residual
concerns
regarding
pre
or
post
natal
toxicity
or
with
the
completeness
of
the
toxicity
or
exposure
databases.
The
total
uncertainty
factors
that
have
been
applied
to
different
noncancer
risk
assessments
include
100
for
short
term
and
intermediate
term
occupational
scenarios.
Chronic
occupational
exposures,
which
are
very
limited
in
scope,
have
an
uncertainty
factor
of
300
because
a
LOAEL
from
the
chronic
dog
study
has
been
used
for
risk
assessment
purposes.
Since
the
FQPA
safety
factor
is
1x,
all
residential
scenarios
have
the
same
factors
applied
to
each
duration
of
exposure
as
well.
Cancer
risk
levels
were
evaluated
based
on
1996
Agency
guidance
by
then
office
director
Dan
Barolo
that
stipulates
a
risk
concern
ranging
from
1x10
4
to
1x10
6
for
occupational
settings
and
1x10
6
for
residential
settings.
For
occupational
handlers,
most
scenarios
have
risks
associated
with
them
that
meet
or
exceed
the
Agency's
uncertainty
factors
for
noncancer
risk
assessments
(i.
e.,
100
for
short
term
and
intermediate
term
and
300
for
chronic)
and
requirements
for
cancer
risk
results
(i.
e.,
range
of
1x10
6
to
1x10
4
as
defined
by
Office
Director
Barolo
in
1996)
at
some
level
of
personal
protection.
Current
carbaryl
labels
typically
require
that
handlers
wear
long
pants,
long
sleeved
shirts,
and
gloves.
Respirators
are
generally
not
required.
For
most
scenarios,
the
noncancer
risks
for
this
personal
protection
ensemble
do
not
meet
Agency
risk
requirements
and
additional
levels
of
personal
protection
are
required
to
achieve
Agency
risk
targets.
In
fact,
in
many
cases
engineering
controls
such
as
closed
loading
systems
or
closed
cab
tractors
are
needed.
The
Agency
does
have
risk
concerns
over
the
use
of
carbaryl
in
some
agricultural
and
other
occupational
settings
(i.
e.,
MOEs
at
any
level
of
personal
protection
are
<100
or
<300,
depending
on
the
duration).
As
would
be
expected,
these
scenarios
with
the
highest
associated
risk
also
have
high
daily
chemical
use
based
on
application
rates
or
high
acreages
treated
or
the
exposures
for
the
scenarios
in
question
are
relatively
high.
Generally,
the
areas
that
appear
to
be
problematic
include:
large
acreage
aerial
and
chemigation
applications
in
agriculture
or
for
wide
area
treatments
such
as
mosquito
control;
airblast
applications
at
higher
rates;
pet
grooming;
and
the
use
of
certain
handheld
equipment
for
applications
to
turf
or
gardens
(e.
g.,
bellygrinder).
This
general
trend
was
essentially
the
same
for
7
both
short
term
and
intermediate
term
exposures.
Risks
for
corresponding
scenarios
based
on
cancer
concerns
were
generally
less
than
noncancer
results
across
all
scenarios.
In
fact,
in
all
but
one
scenario,
cancer
risks
were
<1x10
4
at
current
carbaryl
label
requirements
of
single
layer
clothing,
gloves,
and
no
respirator
for
both
private
growers
and
commercial
applicators.
Higher
levels
of
personal
protection
reduce
this
risk
to
<1x10
4
for
all
scenarios
in
both
populations.
If
a
1x10
6
risk
level
is
specified
as
a
concern,
results
are
similar
in
that
risks
for
a
majority
of
scenarios
are
<1x10
6
at
current
label
requirements.
In
fact,
only
8
of
the
128
scenarios
considered
for
private
applicators
have
cancer
risks
>1x10
6
(and
less
than
1x10
4
)
even
when
the
most
protective
ensembles
of
either
protective
clothing
or
engineering
controls
are
considered.
For
commercial
applicators,
results
indicate
that
risks
for
about
half
of
the
scenarios
considered
are
<1x10
6
at
current
label
requirements
and
that
only
21
of
the
128
scenarios
considered
have
cancer
risks
>1x10
6
(and
less
than
1x10
4
)
even
when
the
most
protective
ensembles
of
either
protective
clothing
or
engineering
controls
are
considered.
Several
data
gaps
were
also
identified
in
many
different
use
areas
that
include:
dust
use
for
animal
grooming
and
in
agriculture;
various
specialized
hand
equipment
application
methods
(e.
g.,
powered
backpack,
power
hand
fogger,
and
tree
injection);
and
nursery
operations
such
as
seedling
dips.
Current
label
requirements
specify
12
hour
Restricted
Entry
Intervals
(REIs)
while
PreHarvest
Intervals
(PHIs)
are
less
than
7
days
for
most
crops
with
some
as
long
as
28
days.
For
all
but
the
lowest
exposure
scenarios
in
some
crops,
MOEs
do
not
meet
or
exceed
required
uncertainty
factors
until
several
days
after
application.
If
short
term
risks
are
considered,
MOEs
meet
or
exceed
the
Agency
uncertainty
factor
generally
in
the
range
of
3
to
5
days
after
application
for
lower
to
medium
exposure
activities
and
from
8
to
12
days
after
application
in
most
higher
exposure
scenarios.
If
intermediate
term
risks
are
considered,
MOEs
are
not
of
concern
based
on
a
30
day
average
exposures
except
for
higher
level
exposures
such
as
harvesting
in
some
crops.
Chronic
exposures
are
of
concern
for
the
cut
flower
industry
but
not
for
other
general
greenhouse
and
nursery
production
activities
based
on
the
most
recent
ARTF
data.
Cancer
risks
were
calculated
for
private
growers
and
professional
farmworkers
with
the
only
difference
being
the
annual
frequency
of
exposure
days.
Cancer
risks
for
private
growers
and
commercial
farmworkers
are
generally
in
the
10
8
to
10
6
range
on
the
day
of
application.
If
a
1x10
4
cancer
risk
is
the
target,
the
current
REI
would
be
adequate
for
all
scenarios
considered
in
the
assessment.
If
a
1x10
6
cancer
risk
is
used,
then
durations
longer
than
the
current
REI
should
be
considered
for
some
cases
which
are
not
considered
low
to
medium
exposures.
It
should
be
noted
that
the
cancer
risk
calculations
are
less
restrictive
than
noncancer
risk
estimates
for
the
same
scenarios
in
all
cases.
Many
mechanized
or
partially
mechanized
processes
are
possibly
associated
with
the
use
of
carbaryl
that
may
limit
or
eliminate
exposures
(e.
g.,
combines
for
grain
harvest).
Mechanized
practices
can
be
divided
into
fully
mechanized
activities
that
meet
the
definition
of
"No
contact"
in
the
Agency's
Worker
Protection
Standard
(WPS)
and
mechanically
assisted
practices
with
potential
for
exposure.
In
the
case
of
fully
mechanized
activities,
the
Agency
does
not
complete
a
quantitative
exposure
assessment
but
applies
criteria
outlined
in
the
Agency's
Worker
Protection
Standard
(WPS).
In
cases
of
partially
mechanized
activities
where
the
potential
for
exposure
exists,
the
Agency
assesses
the
resulting
exposures
similarly
to
those
resulting
from
hand
labor
activities.
The
Agency
also
acknowledges
that
there
is
some
potential
for
exposure
because
individuals
8
engaged
in
fully
mechanized
activities
have
short
term
excursions
from
the
protected
area
for
various
reasons
(e.
g.,
unclogging
machinery
or
equipment
inspection
for
breakage).
In
these
cases,
the
WPS
§
170.112(
c)
Exception
for
short
term
activities
applies.
Several
data
gaps
exist
such
as
an
incomplete
DFR
database
and
a
lack
of
exposure
data
on
partially
mechanized
cultural
practices
where
there
is
a
potential
for
exposure.
Additionally,
because
of
the
number
and
breadth
of
carbaryl
uses,
there
may
be
many
exposure
pathways
where
the
transfer
coefficient
approach
is
not
an
appropriate
model
(e.
g.,
hand
transplanting
where
no
foliar
contact
occurs)
that
have
not
been
quantitatively
addressed
due
to
a
lack
of
data.
For
residential
handlers,
MOEs
associated
with
most
scenarios
(40
of
52
considered)
are
generally
not
of
concern
because
they
exceed
the
Agency's
uncertainty
factors
for
noncancer
risk
assessments
(i.
e.,
MOE
=
100).
The
scenarios
of
concern
involve
the
use
of
dusts
(in
gardens
and
on
pets)
and
for
some
liquid
sprays
on
gardens.
Cancer
risks
were
calculated
for
a
single
day
of
use
then
the
allowable
annual
number
of
days
exposure
was
defined
based
on
a
cancer
risk
limit
of
1x10
6
.
Based
on
a
single
day
of
exposure,
cancer
risks
for
most
scenarios
are
in
the
10
8
to
10
10
range
although
there
is
one
scenario
where
the
risks
slightly
exceed
1x10
6
(dusting
dogs
1.09x10
6
)
even
for
a
single
day
of
use.
It
should
be
noted
that
there
are
5
scenarios
where
the
allowable
days
per
year
of
exposure
is
less
than
or
equal
to
5
which
should
be
considered
in
conjunction
with
the
use/
usage
data
from
Aventis
that
indicates
5
uses
per
year
is
the
84
th
percentile.
The
database
for
carbaryl
is
fairly
complete
compared
to
many
other
chemicals.
Recent,
high
quality
data
generated
by
the
Aventis
Corporation
and
the
ORETF,
of
which
Aventis
is
a
member,
have
been
used
to
address
the
key
residential
uses
of
carbaryl
on
lawns,
flower
and
vegetable
gardens,
and
pets.
Use
and
usage
inputs
also
appear
to
be
essentially
consistent
with
the
information
provided
by
the
Aventis
Corporation
at
the
1998
SMART
meeting.
No
key
data
gaps
have
been
identified
by
the
Agency
at
this
time
for
residential
handlers.
However,
it
is
likely
that
there
are
scenarios
that
remain
unaddressed
by
the
Agency
at
this
time
due
to
a
lack
of
data
or
other
meta
information.
The
Agency
will
address
other
appropriate
scenarios
as
they
are
identified.
The
Agency
considered
a
number
of
residential
postapplication
exposure
scenarios
for
different
segments
of
the
population
including
toddlers,
youth
aged
children
and
adults.
Short
term
and
intermediate
term
noncancer
risks
were
calculated
for
all
scenarios.
Additionally,
cancer
risks
were
calculated
for
the
exposure
scenarios
involving
adults.
In
residential
settings,
the
Agency
does
not
use
REIs
or
other
mitigation
approaches
to
limit
exposures
because
they
are
viewed
as
impractical
and
not
enforceable.
As
such,
risk
estimates
on
the
day
of
application
are
the
key
concern.
9
The
Agency
considered
a
number
of
exposure
scenarios
for
products
that
can
be
used
in
the
residential
environment
representing
different
segments
of
the
population
including
toddlers,
youthaged
children
and
adults.
Short
term
and
intermediate
term
noncancer
MOEs
were
calculated
for
all
scenarios.
Chronic
exposures
from
pet
collars
were
also
considered.
Additionally,
cancer
risks
were
calculated
for
the
exposure
scenarios
involving
adults
where
methods
are
currently
available.
Cancer
risks
were
not
calculated
for
children
per
Agency
policy.
In
residential
settings,
the
Agency
does
not
use
REIs
or
other
mitigation
approaches
to
limit
exposures
because
they
are
viewed
as
impractical
and
not
enforceable.
As
such,
risk
estimates
on
the
day
of
application
are
the
key
concern.
The
Agency
has
short
term
risk
concerns
for
exposures
to
adults
doing
heavy
yardwork,
for
toddlers
playing
on
treated
lawns,
and
for
toddlers
that
have
contact
with
treated
pets.
Activities
associated
with
home
gardening
(e.
g.,
harvesting)
and
golfing
for
adults,
home
gardening
for
youthaged
children
or
any
age
or
activity
considered
in
the
adulticide
mosquito
control
or
oyster
assessment
do
not
have
risk
concerns
even
on
the
day
of
application
(i.
e.,
MOEs
$
100
on
the
day
of
application).
For
adults,
the
MOEs
for
heavy
yardwork
do
not
meet
or
exceed
risk
targets
(i.
e.,
MOE
=
100)
up
to
5
days
after
application.
For
toddlers,
the
Agency
has
concerns
for
pet
treatments
and
also
for
lawn
uses.
In
fact,
pet
uses
never
reach
acceptable
levels
even
30
days
after
application
and
not
until
18
days
at
the
maximum
application
rate
considered
on
turf.
Toddler
MOEs
from
pet
and
turf
uses
represent
total
exposures
from
many
pathways.
For
the
pet
uses,
dermal
and
hand
tomouth
exposures
essentially
both
equally
contribute
to
the
overall
estimate.
For
the
turf
uses,
dermal
and
hand
to
mouth
exposures
are
also
the
key
contributors
to
the
overall
estimates.
The
Agency
does
not
have
intermediate
term
risk
concerns
for
adults
and
youth
aged
children
for
any
of
the
uses
considered
including
lawncare,
home
gardens,
golfing,
and
any
aspect
of
adulticide
mosquito
control.
In
contrast,
the
Agency
does
have
intermediate
term
risk
concerns
for
all
toddler
exposure
scenarios
considered
(i.
e.,
pet
treatments
and
lawncare
uses).
As
with
the
short
term
MOEs,
pet
and
turf
uses
represent
total
exposures
where
the
significant
contributions
to
overall
exposures
are
again
made
equally
from
the
dermal
and
hand
to
mouth
exposure
pathways.
Cancer
risks
were
calculated
only
for
adults
and
were
found
to
be
in
the
10
8
to
10
11
range,
regardless
of
the
scenarios
considered,
on
the
day
of
application
(e.
g.,
lawncare,
golfing
and
gardening).
Risks
did
not
exceed
1x10
6
on
the
day
of
application
for
any
scenario
considered.
All
postapplication
cancer
risks
were
calculated
based
on
an
annual
frequency
of
1
exposure
per
year.
It
is
likely
that
additional
events
could
occur
but
data
linking
postapplication
activities
and
carbaryl
use
patterns
are
not
available.
To
address
this
issue,
the
Agency
calculated
the
number
of
exposures
that
can
occur
under
a
cancer
risk
ceiling
of
1x10
6
and
determined
that
from
20
days
per
year
to
exposures
every
day
of
the
year
could
occur
depending
upon
the
scenario.
Results
indicate
most
activities
can
occur
from
every
day
of
the
year
even
at
residue
levels
present
on
the
day
of
application..
10
Unlike
many
residential
risk
assessments,
the
postapplication
residential
assessment
for
carbaryl
is
based
on
a
number
of
chemical
specific
studies
that
have
been
used
to
calculate
risks
from
turf
uses
(e.
g.,
TTR
study)
and
in
gardens
(i.
e.,
DFR
data).
There
are
no
transferable
residue
data
available
for
pet
uses
which
is
a
key
data
gap.
Additional
data
could
potentially
be
used
to
refine
risk
estimates
for
the
other
settings
such
as
additional
DFR
data
on
different
crops
and
TTR
data
which
are
more
appropriate
for
hand
to
mouth
and
object
to
mouth
exposures.
The
Agency
combines
or
aggregates
risks
resulting
from
exposures
to
individual
chemicals
when
it
is
likely
they
can
occur
simultaneously
based
on
the
use
pattern
and
the
behavior
associated
with
the
exposed
population.
For
carbaryl,
the
Agency
has
combined
risk
values
(i.
e.,
MOEs)
for
different
kinds
of
exposures
associated
with
the
turf
(dermal,
hand
to
mouth,
object
to
mouth,
and
soil
ingestion)
and
pet
scenarios
(dermal
and
hand
to
mouth).
These
represent
the
standard
set
of
exposures
that
are
typically
added
together
when
chemicals
are
used
on
turf
or
on
pets
because
it
is
logical
they
can
co
occur.
Typically,
the
Agency
only
adds
exposures
from
different
exposure
scenarios
together
(e.
g.,
spraying
and
gardening)
when
risks
from
both
are
not
already
a
concern.
For
carbaryl,
there
are
risk
concerns
for
many
residential
handler
scenarios
already
so
the
Agency
did
not
add
risk
values
from
any
postapplication
exposure
together
with
applicator
risks.
It
should
also
be
noted
that
the
Agency
considered
other
sources
of
information
in
the
development
of
this
assessment.
For
example,
carbaryl
residues
were
identified
in
the
Agency
study
entitled
Pesticide
Exposure
in
Children
Living
in
Agricultural
Areas
along
the
United
States
Mexico
Border
Yuma
County,
Arizona.
Preliminary
results
of
this
study
indicate
that
carbaryl
residues
were
identified
in
the
dust
of
20
percent
of
the
152
houses
sampled
and
in
approximately
24
percent
of
25
samples
collected
in
6
schools
in
the
same
region.
Also,
in
a
1995
study
conducted
by
the
Centers
For
Disease
Control,
1000
adults
were
monitored
via
urine
collection.
One
of
the
analytes
measured
in
that
study
(1
napthol)
is
a
potential
metabolite
of
carbaryl
as
well
as
of
napthalene
and
napropamide.
This
metabolite
was
identified
in
86
percent
of
the
1000
adults
monitored
where
the
mean
value
was
17
ppb
and
the
99
th
percentile
was
290
ppb.
These
values
were
not
used
quantitatively
in
the
risk
assessment
for
carbaryl
because
of
the
uncertainties
associated
with
them
such
as
it
cannot
be
clearly
defined
if
carbaryl
or
the
other
chemicals
with
common
metabolites
were
the
key
contributors
to
the
measured
dose
levels.
The
Agency
instead
considers
them
a
qualitative
indicator
that
exposures
in
the
general
population
are
likely
to
occur.
Risk
estimates
using
controlled
study
data
are
protective
when
considered
in
light
of
the
available
monitoring
data.
[Note:
The
Aventis
Corporation
is
in
the
process
of
conducting
a
biomonitoring
study
with
children
who
live
in
households
where
carbaryl
has
been
used.
Preliminary
results
indicate
that
levels
at
the
highest
percentiles
of
the
distribution
are
similar
to
those
predicted
in
the
Agency's
turf
risk
assessments
for
toddlers
which
are
intended
to
represent
the
higher
percentiles
of
the
exposure
distribution.
A
more
detailed
analysis
will
be
completed
upon
submission.]
A
total
of
16
different
studies
were
used
by
the
Agency
to
calculate
carbaryl
risks.
Most
used
carbaryl
(some
handler
studies
did
not)
and
were
scenario
specific.
Each
study
is
considered
to
be
the
best
source
of
information
for
the
scenario
in
which
it
was
used.
Each
of
the
traditional
carbaryl
exposure
studies
are
considered
to
be
high
quality
and
essentially
the
current
state
of
the
art.
There
appear
to
be
some
data
quality
issues
associated
with
the
Washington
State
water
and
11
sediment
monitoring
data.
Where
data
were
not
available,
the
Agency
used
PHED,
the
most
current
policy
for
transfer
coefficients,
and
the
most
current
approaches
for
calculating
residential
exposures
in
the
assessment.
The
Agency
also
extensively
incorporated
the
use
and
usage
information
supplied
by
the
Aventis
Corporation
at
the
1998
SMART
meeting.
The
information
provided
at
that
meeting
essentially
confirm
the
Agency
interpretation
of
carbaryl
use
patterns
which
is
a
key
element
in
the
development
of
a
risk
assessment.
This
risk
assessment
applied
the
latest
exposure
data,
toxicology
information,
and
use
data.
The
overall
results
indicate
that
the
Agency
has
risk
concerns
for
essentially
every
marketplace
where
carbaryl
is
used.
Occupational
handler
risks
can
be
mitigated
through
the
use
of
additional
protective
measures
over
and
above
the
current
label
such
as
engineering
controls
(e.
g.,
closed
cabs
or
loading
systems).
Current
label
REIs
are
12
hours.
For
almost
every
crop/
activity
combination
considered
except
some
low
exposure
activities,
the
current
REI
appears
to
be
inadequate.
Residential
handler
and
postapplication
risks
also
are
of
concern
across
many
areas.
12
1.0
Occupational
and
Residential
Exposure/
Risk
Assessment
1.1
Purpose
This
document
is
the
occupational
and
residential
non
dietary
exposure
and
risk
assessment
for
carbaryl
which
will
be
used
in
the
reregistration
process.
1.2
Criteria
for
Conducting
Exposure
Assessments
An
occupational
and/
or
residential
exposure
assessment
is
required
for
an
active
ingredient
if
(1)
certain
toxicological
criteria
are
triggered
and
(2)
there
is
a
potential
for
exposure
to
handlers
(mixers,
loaders,
applicators)
during
use
or
to
persons
entering
treated
sites
after
application
is
complete.
Toxicological
endpoints
were
selected
for
short,
intermediate,
and
long
term
exposures
(e.
g.,
NOAEL
for
short
and
intermediate
term
dermal
exposures
is
20.0
mg/
kg/
day
based
on
a
21
day
dermal
administration
toxicity
study
in
rats).
Additionally,
carbaryl
has
been
classified
as
a
Group
C
possible
human
carcinogen
(i.
e.,
Q1*
=
8.75
x
10
4
(mg/
kg/
day)
1
).
There
is
a
significant
potential
for
exposure
in
a
variety
of
agricultural,
commercial,
and
residential
settings.
Therefore,
risk
assessments
are
required
for
occupational
and
residential
handlers
and
for
occupational
and
residential
postapplication
exposures
that
can
occur
as
a
result
of
carbaryl
use.
1.3
Summary
of
Hazard
Concerns
The
toxicological
endpoints
that
were
used
to
complete
the
occupational
and
residential
risk
assessments
are
summarized
below
and
in
Table
1
which
has
been
extracted
from
the
latest
HIARC
document
detailing
the
April
2002
meeting,
the
revised
Q1*
memo
of
November
8,
2001
(Brunsman,
TXR
No.
0050265),
and
the
latest
FQPA
SFC
committee
report
from
April
2002.
Effects
were
identified
at
different
durations
of
exposure
ranging
from
short
term
(up
to
30
days)
to
chronic
durations
(every
working
day).
Carbaryl
was
classified
as
a
Class
C
carcinogen
and
is
assessed
for
carcinogenic
risk
using
a
linear,
low
dose
extrapolation
approach
with
a
Q1*
of
8.75
x
10
4
(mg/
kg/
day)
1
.
Carbaryl
is
a
widely
used
carbamate
insecticide
where
the
use
patterns
can
vary
widely
ranging
from
shorter
term
exposures
through
uses
on
virtually
every
working
day.
As
such,
when
the
HIARC
recently
evaluated
the
carbaryl
hazard
database,
endpoints
were
selected
to
address
each
duration
of
exposure.
Exposures
can
occur
to
occupational
users
and
the
general
population
so
both
were
considered
in
this
assessment.
The
short
and
intermediate
term
dermal
risk
assessments
for
carbaryl
are
based
on
NOAEL
of
20.0
mg/
kg/
day
defined
in
a
dermal
toxicity
study
in
rats
(MRID
45630601)
based
on
decreases
in
RBC
and
brain
cholinesterase
in
males
and
females.
The
short
term
inhalation
and
nondietary
ingestion
risk
assessments
for
carbaryl
are
based
on
a
NOAEL
of
1.0
mg/
kg/
day
defined
in
a
developmental
neurotoxicity
study
in
rats
(MRIDs
44393701,
45456701,
45456702,
and
45456703)
based
on
decreased
body
weight
gain,
alterations
in
FOB
measurements,
and
cholinesterase
inhibition
(plasma,
whole
blood,
and
brain).
The
LOAEL
for
this
study
was
observed
at
10
13
mg/
kg/
day.
The
results
of
this
study
were
applied
to
exposure
durations
of
up
to
30
days
and
have
been
applied
only
to
the
inhalation
and
nondietary
ingestion
routes
of
exposure.
The
intermediateterm
inhalation
and
nondietary
risk
assessments
for
carbaryl
(i.
e.,
durations
that
exceed
30
days
but
are
not
chronic
in
nature)
are
based
on
a
NOAEL
of
1.0
mg/
kg/
day
that
was
defined
in
a
subchronic
neurotoxicity
study
in
rats
(MRID
441226
01).
The
LOAEL
for
this
study
is
also
10
mg/
kg/
day.
The
effects
that
were
observed
and
selected
as
the
basis
for
the
endpoint
used
in
risk
assessment
included
decreases
in
plasma,
whole
blood,
red
blood
cell,
and
brain
cholinesterase
activity
and
FOB
changes.
The
results
of
this
study
were
also
applied
only
to
the
inhalation
and
nondietary
ingestion
routes
of
exposure.
The
chronic
risk
assessments
for
carbaryl
are
based
on
a
1
year
dog
feeding
study
(MRIDs
401667
01
and
420228
01).
The
effects
that
were
observed
and
selected
as
the
basis
for
the
endpoint
used
in
risk
assessment
included
decreases
in
plasma,
and
brain
cholinesterase
activity.
A
NOAEL
was
not
defined
in
the
study
so
the
endpoint
that
was
selected
was
the
LOAEL.
The
results
of
this
study
were
applied
to
chronic
exposure
durations
and
have
been
applied
to
all
routes
of
exposure
(i.
e.,
dermal,
inhalation,
and
non
dietary
ingestion).
A
dermal
absorption
factor
of
12.7
percent
was
selected
from
a
rat
dermal
absorption
study
using
radiolabeled
14
C;
this
value
was
used
to
calculate
the
oral
equivalent
dermal
dose
for
noncancer
chronic
duration
exposures
and
for
the
calculation
of
cancer
risks.
No
inhalation
toxicity
studies
were
selected
for
risk
assessment
purposes
so
a
route
to
route
extrapolation
was
used
to
address
risks
from
inhalation
exposures.
No
inhalation
absorption
study
was
conducted,
therefore
a
100
percent
inhalation
absorption
factor
is
used
to
convert
all
inhalation
exposures
to
an
oral
equivalent
inhalation
dose.
The
Agency's
level
of
concern
for
noncancer
risks
(i.
e.,
target
level
for
MOEs)
is
defined
by
the
uncertainty
factors
that
are
applied
to
the
assessment.
The
Agency
applies
a
factor
of
100
in
cases
to
account
for
inter
species
extrapolation
to
humans
from
the
animal
test
species
and
to
account
for
intra
species
sensitivity.
In
cases
where
a
NOAEL
is
not
identified
and
LOAEL
values
have
to
be
used
for
risk
assessments,
the
Agency
generally
applies
an
additional
factor
of
3
as
was
done
with
carbaryl
for
chronic
duration
exposures.
Based
on
the
requirements
of
the
1996
Food
Quality
Protection
Act,
the
Agency
must
also
consider
sensitive
populations
in
its
non
occupational
risk
assessments.
The
Agency
removed
the
FQPA
1x
safety
factor
for
non
occupational
exposures
to
carbaryl
(April
3,
2002
FQPA
SFC
report).
Table
1.
Endpoints
for
Assessing
Non
Dietary
Risks
for
Carbaryl
Type
of
Exposure
Study
Dose
Endpoint
UF
Short
and
Intermediateterm
Dermal
(1
day
to
several
months)
21
Dermal
Toxicity
Study
Using
Technical
Grade
Carbaryl
Rats
(MRID
45630601)
20
mg/
kg/
day
(NOAEL)
Significant
decreases
in
RBC
and
brain
chlolinesterase
(ChE)
100
for
residential
and
100
for
occupational
Short
term
Inhalation
&
Non
dietary
Ingestion
(1
to
30
days)
Developmental
Neurotoxicity
Study
Rats
(MRIDs
44393701,
45456701,
45456702,
45456703)
&
Acute
Neurotoxicity
Study
Rats
(MRIDs
438452
01/
04)
1
mg/
kg/
day
(NOAEL)
Decreased
body
weight
gain;
FOB
changes;
and
decreases
in
plasma,
RBC,
whole
blood,
and
brain
cholinesterase
(ChE)
100
for
residential
and
100
for
occupational
Table
1.
Endpoints
for
Assessing
Non
Dietary
Risks
for
Carbaryl
Type
of
Exposure
Study
Dose
Endpoint
UF
14
Intermediate
term
Inhalation
&
Non
dietary
Ingestion
(30
days
to
several
months)
Subchronic
Neurotoxicity
Study
Rats
(MRID
441226
01)
1
mg/
kg/
day
(NOAEL)
Decreases
in
plasma,
RBC
and
brain
cholinesterase
(ChE)
and
FOB
changes
100
for
residential,
and
100
for
occupational
Chronic
Dermal
&
Inhalation
Dog
Chronic
Toxicity
(MRID
401667
01
and
420228
01)
3.1
mg/
kg/
day
(LOAEL)
Decreases
in
brain
cholinesterase
(ChE)
in
females
300
for
residential,
and
300
for
occupational
Dermal
Absorption
Rat
Dermal
Absorption
Study
12.7
percent
Inhalation
Absorption
100%
inhalation
absorption
value
no
study
available
Q1*
0.
000875
Based
on
increased
incidence
of
hemangiomas/
hemangiosarcomas
in
male
mice
A
series
of
acute
toxicity
tests
were
also
conducted
using
carbaryl
(i.
e.,
outside
of
the
rat
study
which
is
discussed
above).
The
results
indicate
that
carbaryl
is
a
category
III
toxicant
via
the
oral
and
dermal
routes
and
a
category
IV
toxicant
via
inhalation.
It
is
also
a
category
IV
eye
and
skin
irritant.
Results
were
negative
for
dermal
sensitization
and
delayed
acute
neurotoxicity
in
hens.
1.4
Incident
Reports
An
incidence
report
has
been
completed
by
the
Agency.
It
is
considered
with
the
information
included
in
this
document
in
the
overall
human
health
risk
assessment
for
carbaryl.
The
identifying
information
for
the
incident
report
(i.
e.,
date
and
author,
etc.)
is
included
in
the
overall
human
health
risk
assessment.
1.5
Summary
of
Use
Patterns
and
Formulations
Carbaryl
products
are
described
in
this
section.
Additionally,
available
information
that
describes
the
manner
in
which
registered
carbaryl
end
use
products
are
used
is
provided
in
this
section
(e.
g.
use
categories/
sites,
application
methods
and
application
rates).
For
more
detailed
information,
please
refer
to
Appendix
A
of
this
document.
Appendix
A
contains
the
Quantitative
Usage
Analysis
For
Carbaryl
produced
in
1998
by
the
Biological
and
Economic
Analysis
Division
and
the
Use
Profile
Report
For
Carbaryl
also
produced
in
1998
by
the
Biological
and
Economic
Analysis
Division.
15
1.5.1
End
Use
Products
Carbaryl
(1
naphthyl
N
methyl
carbamate)
is
a
broad
spectrum
carbamate
insecticide
marketed
in
a
variety
of
end
use
products
for
both
occupational
and
homeowner
use.
End
use
product
names
include
Adios,
Bugmaster,
Carbamec,
Carbamine,
Crunch,
Denapon,
Dicarbam,
Hexavin,
Karbaspray,
Nac,
Rayvon,
Septene,
Sevin,
Tercyl,
Tornado,
Thinsec,
and
Tricarnam.
Use
sites
include
but
are
not
limited
to:
fruit
and
nut
trees;
vegetable
crops;
field
and
forage
crops;
grapes;
forestry;
lawns
and
other
turf
such
as
golf
courses;
ornamental
trees,
shrubbery,
annuals,
and
perennials;
wide
area
treatment
targets
such
as
residential
mosquito
adulticide
uses;
poultry
production
facilities;
and
companion
animals
(e.
g.,
dogs
and
cats).
Table
2
summarizes
the
technical
and
manufacturing
products
with
their
respective
EPA
registration
numbers.
Table
2:
Technical
and
Manufacturing
Carbaryl
Products
Formulation
EPA
Reg.
No.
(%
active
ingredient)
Technical
34704
707
(99%);
264
324
(99%),
325
(97.5%);
19713
75
(99%)
Manufacturing
Product
264
328
(80%);
769
971
(80%);
19713
369
(50
%);
4816
270
(97.5%),
407
(1%)
Based
on
a
review
(2/
27/
01)
of
the
Office
of
Pesticide
Programs
–
Reference
Files
System
(REFS),
there
are
307
active
product
labels.
Carbaryl
formulations
include
dusts,
emulsifiable
concentrates,
soluble
concentrates;
water
dispersible
granulars;
flowable
concentrates;
wettable
powders;
granulars;
baits;
pet
dips
and
pet
shampoos;
aerosol
sprays;
ready
to
use
pump
sprayers;
and
pet
collars
(i.
e.,
treated
articles).
Table
3
outlines
the
formulations
and
EPA
registration
numbers
for
labels
of
carbaryl
end
use
products
according
to
REFs.
Many
of
the
products
described
in
Table
3
can
be
used
in
a
variety
of
settings
ranging
from
agriculture
and
commercial
facilities
to
residential
areas.
Some
products
are
marketed
in
a
single
marketplace
while
others
are
sold
for
use
in
each
setting.
From
sales
information
provided
by
the
Aventis
Corporation
at
the
SMART
meeting
with
EPA
on
September
24,
1998
approximately
34
percent
of
carbaryl
end
use
products
are
used
in
the
homeowner/
residential
setting
while
59
percent
is
used
in
agriculture.
The
remaining
7
percent
is
used
in
nursery,
landscape
and
golf
course
industries.
16
Table
3:
End
Use
Product
Formulations
and
EPA
Reg.
Number.
Formulation
Type
EPA
Registration
Number
(Percent
Active
Ingredient)
Emulsifiable
Concentrates
&
Flowable
Concentrates
7401
83,
210
(25%),
208(
13%);
19713
49(
43.4%),
89
(22.5%),
131(
49%);
51036
66(
43.3%),
123(
22.5%);
10163
60
(43.7%
),
134(
80%);
10107
42
(43.4%),
44
(23.4%);
11715
207,
209,
229
(42.6%);
33955
533
(23.4%);
67517
31(
5%);
9779
260
(43.4%);
8660
133
(11.7%);
264
321
(40%),
333
(44.1%),
334(
22.5%),
335
349
(43%),
422
(48%)
;
2217
366
(50%),
600
(23.4%);
4
59(
0.5%),
122
(0.
3%);
237
(22.5%);
192
174
(21.3%);
239
2628(
21.3%);
270
286
(23%);
407
383
(24%);
5905
251
(40.38%);
5887
102,
162
(0.
3%)
0;
769
493(
42.85%),
573
(23%),
648,
865,
883
(21.3%);
28293
222(
21.3%);
59144
6
(21.3%);
46515
35
(11.7%);
16
76
(21.3%);
34704
447(
43%);
8660
70
(24.4%);
909
103(
21.3%);
46515
36(
21.3%);
7401
38,
62
(5%),
386
(13.5);
802
585
(21.3%);
50383
10
(22.5%);
54705
4
(41.2%);
16
76
SLNs:
CO8800
1300,
FL8900
3700,
HI9700
0300,
NC9600
0300,
OH9600
0300,OR9500
0600,PA9600
0200,
VA9500
0100,
WA9700
2200
Wettable
Powders
&
Soluble
Granules
33955
450
(50%);
51036
151(
80%);
19713
50
(80%),
52(
50%),
363
(85%),
84
(95%);
10163
133
(80%);
9779
294(
90%);
8660
60
(50%);
5905
517
(80%);
264
314
(50%),
315
(85%),
316
(80%),
427
(39.7%),
526
(80%);
5481
65
(50%),
242
(0.
5%),
271
(50%);
5887
86
(50%);
2217
389
(50%);
4
157
(13.5%),
387
(50%);
769
574
(80%),
868
(50%),
919
(21.3),
920,
834,
972
(50%);
70
285
(50%);
1386
445;
34704
350(
50%),
619
(80%);
1386
455;
16
99(
50%);
407
287(
50%);
228
249(
5%)
SLNs:
CA7802
070,
CA8100
5900,
CA8300
0700,
CA8300
0701,
CA8300
0702,
FL8900
3600,
HI9600
0900,
NC8200
0700,
NC8700
0702,
WA9000
1300
Dusts
67517
32
(10%);
9198
141
(2.
37%),
147(
5%),
148(
10%);
4
29
(1.
25%),
143
(5%),
413,
415;
16
12
(2%),
98
(10%),
121(
5%),
127(
2%);
239
1349,
1513
(10%),
2181
(5%);
270
272
(5%);
70
165
(10%),
166(
5%);
16
27
(5%);
67572
16
(5%),
36
(10%);
59144
3
(5%),
5
(10%);
50383
16
(5%);
49585
4,
24
(5%),
26(
10%);
435763
5%);
34911
6
(5%);
28293
6,
10,
301,
302(
5%),
14(
12.5%),
18,
102,
301
(10%),
237(
5%);
19713
53,212
10%),
213(
5%),
244(
80%);
829
128
(5%),
131(
1.75%),
142(
50%),
200(
10%);
2217
383,
572
(5%);
272475
(5%);
2781
25(
5%);
769
559,
611,
613,
642,
647,
906
(5%),
835(
1.75%),
229,
612,
665(
10%),
614
12.5%);
655
788(
5%),
789
(10%);
11715
250(
12.5%),
255,
294(
5%),
292(
10%);
9779
74
(5%);
8660
72,234
5%),
241(
10%);
7401
69,
310(
5%),
291(
1.75),
334(
2%),
81,
166,
154(
10%);
5887
43(
5%);
5481
275,282
321(
2%),
58,
98,
253,
283,
316,
451
(5%),
312,
323(
7.5%),
108,
277,
294(
10%),
190(
46%);
4758
7,
32
34(
5%);
4306
10(
5%);
3342
100(
5%);
5887
77(
0.3%);
2935
193
(5%),
320(
10%);
3342
51(
5%),
53(
2%),
56
1.75%),
69(
10%);
2393
375(
5%);
1386
451,
630(
5%)
633(
10%);
869
118(
5%).
180(
10%);
802
442(
5%);
572
107(
5%);
192
70(
5%);
228
251,
252(
5%);
51036
13(
10%),
48(
5%);
33955
462(
5%);
10163
124(
10%);
10159
2(
5%);
10107
43(
10%),
45(
5%);
9779
81(
10%),
61(
50%);
36272
14(
5%);
37425
13(
12.5%);
497843
12.5%);
71949
11(
10%),
10(
5%)
Granular
28293
233
(6.
3%);
9198
142
(3.
5%);
5887
94,
170
(5%);
769
728
(5%),
970*(
3.5%),
976(
2%);
59144
26*(
1%),
27*
(2%);
34704
289(
10%),
373*
(5%);
32802
58(
3.9%),
59*
(1.
43);
10404
61*(
6.3%),
62*(
4%);
8378
31*(
4.3%),
36*(
1.43%);
5481
89(
10%),
90,
97*(
5%),
95*(
4%),
100*(
5%);
264
430*(
7%);
90983
5%);
869
228*(
2%);
9779
156*(
5%);
8660
28*
(1%);
7401
43(
3.34%),
51(
1.8%);
192
199
(2%);
4142
4.6%);
572
204(
8%);
802
351(
5%);
264
429(
7%);
5905
169(
10%),
180(
180%);
9198
106(
6.2%),
139
4.6%),
143(
4%),
144(
4.55%),
145(
6.3%),
146(
8%);
19713
334(
10%);
51036
225(
5%);
67572
81(
1%)
Bait
67650
2
(2%);;
61282
4,
21(
10.04%),
16,
22
(5%);
42057
39
(4%);
32802
51
(5%);
10370
152
(5%);
8278
3
(5%);
769
729,
730
(5%);
802
493
(5%);
31282
22*
(5%);
4
333*
(5%);
1386
655*(
5%);
10107
143*
(5%);
869
119(
5%);
7401
72*(
4%),
148
(2%),
265(
4%);
8119
5
(5%);
239
2514
(5%);
70
244(
5%);
829182
4.25%),
285
(5%);
961
290(
7.15%),
355(
5.93%);
264
312
(10%),
320(
5%);
2393
209(
5%);
6973
10(
4%);
7729
7(
5%);
8660
111(
5%),
188(
4.55%);
10163
32(
5%);
11656
20(
4%),
21(
5%);
28293
235(
5%);
34704
23,483
5%);
49399
1(
2%),
2(
5%);
51036
61(
5%),,
185,
210(
13%),
204,
227(
1.3%),
286(
10%);
59639
52,60
5%);
2935
366(
5%);
19713
494(
5%);
34911
8(
4%);
67572
56(
4%);
71949
12(
5%)
SLNs:
FL9200
0800
Dips,
Shampoos
28293
8(
60%);
2097
8
(0.
5%)
Pet
collars
(treated
articles)
2724
272
(8.
5%),
273
(16%)
Table
3:
End
Use
Product
Formulations
and
EPA
Reg.
Number.
Formulation
Type
EPA
Registration
Number
(Percent
Active
Ingredient)
17
Ready
to
Use
Pump
Sprayers
&
Aerosol
Cans
1910
2
(1%);
67572
75
(0.
126%);
9444
98,
190
(0.
5%);
769
977(
0.126%);
8119
3
(5%);
28293
97
(0.
5%)
1.5.2
Mode
of
Action
and
Targets
Controlled
Carbaryl
(1
naphthyl
methylcarbamate)
belongs
to
the
carbamate
class
of
pesticides.
Like
the
other
carbamates,
carbaryl
antagonizes
acetylcholine
and
competes
for
binding
sites
on
the
enzyme
cholinesterase.
In
agriculture
and
residential/
recreational
areas,
carbaryl
is
used
as
a
contact
insecticide
recommended
for
use
against
pests
in
a
variety
of
settings.
These
pests
include
(i.
e.,
based
on
information
provided
on
labels
and
in
the
Use
Profile
Report
included
as
Appendix
A
of
this
document):
°
On
Fruit
Trees
and
Nut
Trees:
apple
aphid,
apple
maggot,
apple
mealybug,
apple
rust
mite,
apple
sucker,
bagworms,
California
pearlslug,
codling
moth,
eastern
tent
caterpillar,
European
apple
sawfly,
eyespotted
bud
moth,
fruittree
leafroller,
green
fruitworm,
Japanese
beetle,
lesser
appleworm,
lygusbugs,
orange
tortrix,
pear
leaf
blister
mite,
pear
psylla,
pear
rust
mite,
periodical
cicada,
plum
curculio,
redbanded
leafroller,
scale
insects,
tarnished
plant
bug,
tentiform
leafminers.
White
apple
leafhopper,
wooly
apple
aphid,
navel
orangeworm,
peach
twig
borer,
san
Jose
scale,
European
raspberry
aphid,
omnivorous
leafroller,
raspberry
sawfly,
rose
chafer,
snowy
rose
tree
cricket,
blueberry
maggot,
sherry
fruitworm,
cranberry
fruitworm,
European
fruit
lecanium,
chestnut
weevil,
avocado
leafroller,
california
orangedog,
citrus
cutworm
citrus
root
weevil,
fullers
rose
beetle,
orange
tortrix,
western
tussock
moth,
west
Indian
sugarcane
borer,
filbert
aphid,
filbert
leafroller,
filbertworm,
eight
spotted
forester,
grape
berry
moth,
grape
leaffolder,
grape
leafhopper,
June
beetles,
saltmarsh
caterpillar,
western
grapeleaf
skeletonizer,
western
yello
striped
armyworm,
olive
scale,
apple
pendemis,
cucumber
beetles,
European
earwig,
lesser
peach
tree
borer,
oriental
fruit
moth,
peach
twig
borer,
tarnished
plant
bug,
tussock
moth,
black
margined
aphid,
fall
webworm,
pecan
leaf
phylloxera,
pecan
nut
casebearer,
pecan
spittlebug,
pecan
stem
phylloxera,
pecan
weevil,
twig
girdler,
walnut
caterpillar,
calico
scale.
°
On
Terrestrial
Food
and
Feed
Crops:
blister
beetles,
Mexican
bean
beetles
alfalfa
caterpillar,
beanleaf
beetle,
cucumber
beetle,
grasshoppers,
green
cloverworm,
japanese
beetle,
leafhoppers,
three
cornered
alfalfa
hopper,
thrips,
velvetbean
caterpillar,
alfalfa
weevil
larvae,
armyworm,
cloverhead
weevil,
cotton
fleahopper,
cotton
leafworm,
flea
beetle,
striped
blister
beetle,
boll
weevil,
bollworms,
cotton
leafperforator,
plant
bugs,
saltmarsh
caterpillar,
corn
earworm,
corn
rootworm
adults,
southwestern
corn
borer,
japanese
beetle,
European
corn
borer,
cutworms,
Egyptian
alfalfa
weevil
larvae,
Essex
skipper,
European
alfalfa
beetle,
fall
armyworm,
lygus
bugs,
webworms,
yellowstriped
armyworm,
asparagus
beetle,
apache
cicada,
stinkbugs,
tarnished
plant
bug,
webworm,
cowpea
curculio,
aster
leafhoppers,
harlequin
bug,
imported
cabbageworm,
melonworm,
18
pickleworm,
squash
bugs,
pink
bollworm,
range
caterpillars,
thrips,
white
grubs,
white
fringed
beetle
adult,
Colorado
potato
beetle,
pea
leaf
weevil,
tomato
fruitworm,
tomato
hornworm,
grape
colaspis,
sweet
potatoweevil;,
tortoise
beetles,
green
June
beetle
grubs,
budworms,
cereal
leaf
beetle
(except
in
CA).
°
On
Ornamentals:
blister
beetle,
flea
beetle,
boxelder
bug,
japanese
beetle,
June
beetle,
lace
bug,
leafhopper,
leafroller,
mealybug,
plant
bug,
psyllids,
rose
aphid
thrips,
apple
aphid,
bagworm,
birch
leafminer,
cankerworm,
eastern
spruce
gall
aphid,
elm
leaf
aphid,
elm
leaf
beetle,
gypsy
moth,
mimosa
webworm,
oak
leafminer,
orange
tortrix,
periodical
cicada,
puss
caterpillar,
rose
aphid,
rose
slug,
sawfly,
scale,
tent
caterpillar,
thrips,
willow
leaf
beetle.
°
On
Lawns/
Turf:
ants,
bluegrass
billbug,
chinch
bug,
cut
worm,
crane
fly,
earwig,
European
chafer,
fall
armyworm,
fleas,
green
June
beetle,
leafhopper,
millipedes,
mosquitoes,
sod
webworms
(lawn
moths),
ixoides
spp.(
deer
tick,
bear
tick,
black
legged
tick),
amblyomma
spp.(
lone
star
tick).
°
Poultry:
northern
fowl
mite,
chicken
mite,
lice,
fleas,
bedbugs,
fowl
ticks.
°
In
and
Around
Buildings:
indoors:
ants,
crickets,
firebrats,
silverfish,
bees,
wasps,
brown
dog
ticks,
fleas,
carpenter
ants,
scorpions,
centipedes,
earwigs,
millipedes,
cockroaches,
spiders.
°
Outdoors:
ants,
bees,
wasps,
brown
dog
ticks,
carpenter
ants,
centipedes,
cockroaches,
crickets,
earwigs,
firebrats,
fire
ants
(mound
treatment),
silverfish,
fleas
millipedes,
scorpions
and
spiders.
°
Public
Health/
Wide
Area:
mosquitoes.
°
Dogs
and
cats:
fleas
and
ticks,
on
animal
and
in
bedding/
housing.
1.5.3
Registered
Use
Categories
and
Sites
An
analysis
of
the
current
labeling
and
available
use
information
was
completed
using
the
Office
of
Pesticide
Programs–
Label
Use
Information
System
(LUIS)
in
addition
to
REFs.
Carbaryl
is
registered
for
use
in
a
variety
of
occupational
and
homeowner/
residential
scenarios.
For
reasons
of
clarity
in
the
risk
assessment
process,
the
use
patterns
have
been
described
in
a
manner
that
delineates
occupational
from
homeowner/
residential
uses.
Occupational
Use
Sites
Occupational
populations
are
potentially
exposed
while
making
carbaryl
applications
to
the
following
targets
or
after
contact
with
the
treated
targets
after
previous
carbaryl
applications.
The
following
list
is
a
summary
of
occupational
use
sites
as
described
in
the
Carbaryl
Use
Profile
prepared
by
Don
Atwood
of
the
Biological
and
Economic
Analysis
Division
in
November
of
1998
19
(see
Appendix
A).
[Note:
Modifications
to
the
Use
Profile
have
been
made
based
on
label
deletions
and
modifications
since
November
of
1998.]
Terrestrial
Food
Crop
Cucurbits
cucumber,
melons,
Chinese
okra,
pumpkin,
and
squash
Flavoring
and
Spice
Crops
dill
Fruiting
Vegetables
tomato,
eggplant
and
pepper
Grain
Crops
prosso
millet
Leafy
and
Stem
Vegetables
beets,
broccoli,
brussels
sprouts,
cabbage,
chinese
cabbage,
cauliflower,
celery,
Swiss
chard,
collards,
dandelion,
endive
(escarole),
hanover
salad,
kale,
kohlrabi,
lettuce
(head,
crisphead
types,
leaf
types),
mustard,
parsley,
rhubarb,
and
spinach
Miscellaneous
Fruits
olive
Miscellaneous
Vegetables
asparagus
Nut
Crops
almond,
chestnut,
filbert
(hazelnut),
pecan,
pistachio,
and
walnut
(english/
black)
Pome
Fruits
crabapple,
pear,
and
quince
Root
Crop
Vegetables
beets,
carrot
(including
tops),
horseradish,
radish,
rutabaga,
salsify,
and
sweet
potato
Small
Fruits
blackberry,
blueberry,
boysenberry,
caneberries,
cranberry,
dewberry,
loganberry,
raspberry
(black,
red),
and
strawberry
Specialized
Field
Crops
okra
Stone
Fruits
apricot,
cherry,
nectarine,
peach,
plum,
and
prune
Terrestrial
Food+
Feed
Crop
Citrus
Fruits
grapefruit,
lemon,
lime,
orange,
tangerine
Crops
Grown
for
Oil
field
corn,
flax,
and
sunflower
Miscellaneous
Fruits
longan
and
mango
Fiber
Crops
flax
Fruiting
Vegetables
tomato
Grain
Crops
field
corn,
rice,
sorghum
and
wheat
Groups
of
Agricultural
Crops
Which
Cross
Established
Crop
Groupings
cotton,
peanuts,
peas,
sorghum,
soybeans,
and
vegetables
Leafy
and
Stem
Vegetables
mustard
and
turnip
Nut
Crops
almond,
chesnuts,
filberts,
pecans,
pistachios
and
walnuts
Pome
Fruits
apple,
pears,
loquats,
crabapples
and
oriental
pears
Root
Crop
Vegetables
parsnip,
white/
irish
potato,
salsify,
and
turnip
Seed
and
Pod
Vegetables
beans
(dried
type),
succulent
beans
(lima
and
snap),
cowpea/
blackeyed
pea,
cowpea/
sitao,
lentils,
peanuts,
peas
(dried
type),
field
peas,
southern
peas,
succulent
peas,
and
soybeans
(edible)
Small
Fruits
grapes,
caneberries,
blueberries,
cranberries
and
strawberries
Specialized
Field
Crops
popcorn,
sweet
corn,
and
sunflower
Sugar
Crops
sugar
beet
20
Terrestrial
Feed
Crop
Forage
Grasses
corn,
grass
forage/
fodder/
hay,
millet
(proso),
pastures,
rangeland,
rice,
sorghum,
and
wheat
Forage
Legumes
and
Other
Nongrass
Forage
Crops
alfalfa,
clover,
cotton,
and
trefoil
Grain
Crops
proso
millet
Groups
of
Agricultural
Crops
Which
Cross
Established
Crop
Groupings
grasses
grown
for
seed
Terrestrial
non
food
crop
Agricultural
Uncultivated
Areas
Agricultural
fallow/
idleland
and
Agricultural
rights
of
way/
fencerows/
hedgerows
Commercial/
Industrial/
Institutional
Premises
and
Equipment
Commercial/
Institutional/
Industrial
premises/
Equipment
(Outdoor)
Fiber
Crops
Forest
Trees
christmas
tree
plantations
Groups
of
Agricultural
Crops
Which
Cross
Established
Crop
Groupings
Fruits
(unspecified)
Nonagricultural
Uncultivated
Areas
Outdoor
buildings/
structures,
rights
ofway
fencerows/
hedgerows,
uncultivated
areas/
soils,
and
recreational
areas
Ornamental
Lawns
and
Turf
commercial/
industrial
lawns,
golf
course
turf,
Ornamental
sod
farm
(turf),
and
recreational
area
lawns
Specialized
Field
Crops
tobacco
Wide
Area/
General
Outdoor
Treatments
fencerows/
hedgerows,
urban
areas,
and
wide
area/
general
outdoor
treatment
(public
health
use)
Terrestrial
non
food+
outdoor
residential
Nonagricultural
Uncultivated
Areas
rights
of
way/
fencerows/
hedgerows
Ornamental
Herbaceous
Plants
Ornamental
Lawns
and
Turf
Ornamental
Nonflowering
Plants
Ornamental
Woody
Shrubs
and
Vines
Ornamental
and/
or
Shade
Trees
Wide
Area/
General
Outdoor
Treatments
fencerows/
hedgerows
Terrestrial+
Greenhouse
non
food
crop
Ornamental
Herbaceous
Plants
Ornamental
Woody
Shrubs
and
Vines
Ornamental
and/
or
Shade
Trees
Animal
Uses
Poultry
(chickens,
ducks,
geese,
game
birds,
turkeys)
Livestock
(cattle,
sheep,
horses,
etc.)
21
Pets
(cats
and
dogs)
Aquatic
food
crop
Aquatic
Sites
commercial
fishery
water
systems
Grain
Crops
rice
Small
Fruits
cranberry
Fish
&
Shellfish
Uses
oyster
beds
Aquatic
non
food
industrial
Aquatic
Sites
Drainage
systems
Forestry
Forest
Trees
forest
plantings
(reforestation
programs,
tree
farms,
tree
plantations,
etc),
forest
trees
(all
or
unspecified),
maple
(forest),
and
shelterbelt
plantings
Homeowner/
Residential
Use
Sites
Residential
and
non
occupational
use
sites
include
those
labeled
for
outdoor
applications
such
as
on
lawns,
gardens,
and
ornamentals
as
well
as
for
use
on
companion
animals
such
as
dogs
or
cats.
There
are
no
labels
that
allow
indoor
premise
treatments
(e.
g.,
crack
and
crevice
or
broadcast).
Carbaryl
can
be
purchased
and
used
by
homeowners
in
residential
settings.
It
can
also
be
used
by
professionals
such
as
LCOs
(Lawn
Care
Operators)
in
residential
settings.
Exposures
can
also
occur
as
a
result
of
uses
in
other
areas
frequented
by
the
general
population
such
as
parks
and
recreational
areas,
treated
Christmas
tree
plantations,
and
forests.
Veterinary
clinic
uses
can
also
result
in
exposures
due
to
contact
with
treated
animals.
The
following
is
a
list
of
use
sites
in
the
residential
environment.
°
Trees:
fruits,
nuts,
and
shade/
ornamental;
°
Lawns
and
Ornamentals:
lawns,
house
perimeter,
shrubs
and
flowers;
°
Vegetables:
beans,
berries,
broccoli,
brussels
sprouts,
cabbage,
carrots,
cauliflower,
corn,
cowpeas,
cucumbers,
eggplant,
herbs,
lettuce,
melon,
okra,
onions,
peas,
peppers,
potatoes,
summer
squash,
tomatoes;
°
Pets:
dogs,
cats,
and
housing/
bedding;
and
°
Fire
Ant
Mounds
22
1.5.4
Application
Parameters
Application
parameters
are
generally
defined
by
the
physical
nature
of
the
use
site,
the
physical
nature
of
the
formulation
(e.
g.,
formula
and
packaging),
by
the
equipment
required
to
deliver
the
chemical
to
the
use
site,
and
by
the
application
rate
required
to
achieve
an
efficacious
dose.
As
such,
the
application
parameters
for
major
crop
groups
or
application
targets
have
been
summarized
by
identifying
the
maximum
application
rates
for
each
group
and
the
equipment
that
can
be
used
to
make
applications.
All
of
the
information
presented
below
are
summarized
from
the
Agency's
QUA
and
Use
Profile
documents
included
as
Appendix
A,
from
the
SMART
meeting
information
provided
to
the
Agency
on
September
24,
1998
by
the
Aventis
Corporation,
from
current
carbaryl
labels,
and
from
the
use
summary
used
in
the
dietary
exposure
aspect
of
the
risk
assessment.
Selected
crop
groupings
and
application
targets
along
with
corresponding
typical
(if
available)
and
maximum
application
rates
that
are
used
in
the
risk
assessment
are
presented
in
Table
4
below.
Additionally,
the
equipment
that
can
be
used
to
make
applications
are
also
discussed
below
for
each
crop
group
considered.
The
Agency
could
not
quantitatively
address
the
use
of
carbaryl
in
every
specific
crop
or
setting
in
its
risk
assessment
because
of
the
associated
level
of
complexity
that
would
be
added
to
the
risk
assessment
process.
Instead,
representative
crops
or
targets
were
selected
that
were
used
as
the
basis
for
the
assessment.
A
broad
range
of
rates
were
used
to
ensure
that
use
scenarios
would
be
addressed
in
the
range
of
values
selected.
Table
4:
Representative
Application
Rates
Considered
in
Risk
Assessment
Crop
or
Target
Occupational
Products
Residential
Products
lb
ai/
1000
ft
2
(units
may
vary)
lb
ai/
A/
acre
(units
may
vary)
max.
apps/
season
lb
ai/
season
Average
Rates
Alfalfa,
clover,
trefoil
1.
5
1/
cutting
1.
5/
cutting
1.
1
Asparagus
2
4
postharvest
3
broadcast
2
postharvest
6
broadcast
10
postharvest
0.9
0.
023
0.
094
Beans
(fresh
&
dried),
cowpeas,
peas
1.5
4
6
0.
9
0.012
0.047
Beets,
carrot,
horseradish,
radish,
parsnip
2
foliar
2.2
soil
broadcast
6
foliar
4
soil
6
0.
8
0.012
0.047
Blueberries
2
foliar
0.5
lb/
1000
ft
2
soil
5
10
1.
7
0.012
0.047
Cole
Crops
(broccoli,
brussel
sprouts,
cabbage,
cauliflower,
chinese
cabbage,
collards,
kale,
kohlrabi,
mustard
greens)
2
foliar
2.2
soil
broadcast
4
6
0.8
0.
012
0.047
Caneberries
2
foliar
2.2
soil
broadcast
5
4
10
Not
specified
1.7
0.
012
0.047
Celery,
Dandelion
2
foliar
2.2
soil
broadcast
4
6
1.0
0.
012
0.047
Citrus
16
(foliar
in
CA
only)
10
(foliar
in
FL
only)
7.5
foliar
1
lb/
100
gal.
1
Not
specified
8
Not
specified
20
Not
specified
20
Not
specified
2.7
to
3.4
(lemons
&
oranges)
0.023
0.176
Table
4:
Representative
Application
Rates
Considered
in
Risk
Assessment
Crop
or
Target
Occupational
Products
Residential
Products
lb
ai/
1000
ft
2
(units
may
vary)
lb
ai/
A/
acre
(units
may
vary)
max.
apps/
season
lb
ai/
season
Average
Rates
23
Corn
(field
and
pop)
2
4
8
1.
0
0.012
0.047
Corn
(sweet)
2
foliar
2.2
soil
broadcast
8
4
16
Not
specified
1.3
0.
012
0.047
Cranberry
2
5
10
2.0
0.
012
0.047
Cucurbits
(cucumber,
melon,
pumpkin,
squash)
1
6
6
1.
1
0.012
0.047
Fruiting
Vegetable
(tomato,
eggplant,
pepper)
2
7
8
1.
0
0.012
0.047
Grapes
2
5
10
1.4
0.
012
0.047
Grasses
Grown
For
Seed
1.5
2
3
0.
8
(based
on
hay)
Leafy
Vegetable
(head
and
leaf
lettuce,
endive,
mustard
green)
2
foliar
2.2
soil
broadcast
5
4
6
Not
specified
1.1
0.
012
0.047
Nuts
(almond,
chestnut,
pecan,
pistachio,
walnut,
etc.),
foliar
or
dormant/
delayed
5
4
15
2.5
(pecans)
0.047
0.12
Nuts
(almond,
chestnut,
pecan,
walnut),
foliar
in
CA
1
lb
ai/
100
gal
Not
specified
Not
specified
Not
specified
0.047
0.12
Ornamental
2.2
or
2%
solution
1.
5
0.023
Oyster
beds
(SLN
only)
10
Not
specified
Not
specified
Peanut
2
5
8
0.
8
0.012
0.047
Pome
fruit
3
8
15
1.
2
(based
on
apples)
0.012
0.07
Poultry
1/
1000
ft
2
broiler
0.64
0.76/
100
layers
Potatoes
&
Tubers
(turnips)
2
6
6
0.8
Rangeland
pastures
1
1
1
0.
9
Rice
1.5
2
4
1.
1
Right
of
Way
1.
5
3
0.
4
Sorghum
2
4
6
1.
1
Stone
fruit
(apricot,
cherry,
nectarine,
peach,
plum/
prune),
foliar
or
dormant/
delayed
3
4
CA
only
3
foliar
&
1
dormant/
delayed
14
1.1
0.
047
0.12
Stone
fruit
(apricot,
cherry,
nectarine,
peach,
plum/
prune),
foliar
1
lb
ai/
100
gal
Not
specified
Not
specified
Not
specified
0.047
0.12
Strawberries
2
5
10
1.4
0.
012
0.047
Sugar
beets
1.
5
to
2
2
to
4
4
1.3
0.
012
0.047
Sweet
Potatoes
2
foliar
8
lb/
100
gal
drip
8
foliar
Not
specified
8
foliar
1.2
1.6
foliar
Not
specified
0.012
0.047
Sunflower
1.
5
2
3
0.7
0.
012
0.047
Tobacco
2
4
8
1.
1
Tree
farm
1
2
0.
7
Turf/
golf
8
liquids
9
granulars
0.
8/
1000sf
2
to
4
0.
047
to
0.25
(lawns)
[max
levels
for
different
products]
Wheat,
flax
1.5
2
3
0.
8
Ants
2%
sol
2%
sol
Mosquito
Control
2
Outdoor
Banding
2%
sol
2%
sol
Table
4:
Representative
Application
Rates
Considered
in
Risk
Assessment
Crop
or
Target
Occupational
Products
Residential
Products
lb
ai/
1000
ft
2
(units
may
vary)
lb
ai/
A/
acre
(units
may
vary)
max.
apps/
season
lb
ai/
season
Average
Rates
24
Domestic
Animals
(e.
g.,
cats/
dogs)
Dust
0.2
lb
ai/
dog
Sha.
0.01
lb
ai/
dog
Dust
0.2
lb
ai/
dog
Sha.
0.01
lb
ai/
dog
Domestic
Animals
(e.
g.,
cats/
dogs)
1.3
oz/
dog
collar
1.3
oz/
dog
collar
°
Tree
Crops:
The
application
rate
for
commercial
crops
is
between
2
to
6
lb
ai
per
acre
for
most
crops.
Citrus
rates
are
higher
at
16
lb
ai
per
acre
(CA
only).
Equipment
for
commercial
use
is
airblast,
aerial
and
chemigation.
°
Grapes:
The
application
rate
for
commercial
crops
is
2
lb
ai
per
acre.
Equipment
for
commercial
use
is
airblast,
over
the
row
groundboom,
power
duster,
aerial
and
chemigation.
°
Field,
forage,
fiber,
small
fruit
(i.
e.,
berries)
and
vegetable
crops:
The
application
rate
for
commercial
crops
is
1
to
2
lb
ai
per
acre.
Equipment
for
commercial
use
is
groundboom,
aerial
and
chemigation.
°
Non
crop
areas:
The
application
rate
for
commercial
area
is
1
lb
ai
per
acre.
Equipment
is
groundboom,
aerial
and
right
of
way
sprayer.
°
Ornamentals:
The
application
rate
for
commercial
area
is
2.2
lb
ai
per
acre.
Equipment
for
commercial
use
is
low
pressure
handwand,
backpack,
high
pressure
handwand
and
airblast/
mist
blower.
°
Lawn
Care
(professional
certified
operator
(pco)):
The
application
rate
for
pco
applicators
is
up
to
8
lb
ai
per
acre.
The
application
equipment
is
hand
held
power
sprayers
and
granular
spreaders.
°
Evergreens
in
large
stands:
the
application
rate
for
commercial
crops
is
1
lb
per
acre
or
1.8
lb
ai
per
1000
square
feet
to
the
seed,
mound
or
trunk.
Equipment
used
for
commercial
areas
is
airblast,
aerial,
and
high
pressure
handwand.
°
Poultry:
The
application
rates
for
commercial
poultry
production
vary
from
0.0048
lb
ai
per
bird,
to
0.08
lb
ai
per
1000
square
feet
and
are
also
reported
as
1
lb
ai
per
3.1
gallons.
Application
equipment
for
commercial
production
includes,
compressed
air
sprayer,
fogger,
backpack
sprayer
and
mist
blower
and
power
sprayers.
°
Homeowner
fruits
and
nuts:
0.0039
lb
ai
per
gallon
or
up
to
0.8
lb
ai
per
5
trees.
Application
equipment
includes,
hose
end
sprayer
and
hand
held
pump
sprayer.
25
°
Homeowner
vegetables:
The
application
rate
for
homeowner
vegetable
gardens
is
0.0026
lb
ai
per
20
foot
row.
The
application
equipment
includes,
hose
end
sprayer,
hand
held
pump
sprayer,
hand
held
dusters
and
shaker
cans.
°
Homeowner
lawn
care:
Maximum
application
rates
range
from
2
lb
ai/
acre
(0.047
lb
ai/
1000
ft2)
up
to
almost
11
lb
ai
per
acre
(0.25
lb
ai/
1000
ft2)
depending
upon
the
product/
packaging
and
the
pest.
For
the
vast
majority
of
products
(e.
g.,
professional
application
to
residential
lawns
that
could
result
in
postapplication
exposures
and
open
packaging
for
homeowners)
the
maximum
application
rates
are
8
lb
ai/
acre
for
liquids
and
9
lb
ai/
acre
for
granules.
Equipment
for
homeowner
use
is
hose
end
sprayer,
granular
spreader,
and
belly
grinder.
°
Homeowner
ornamentals:
The
application
rate
for
homeowner
ornamentals
is
0.02
lb
ai
per
gallon
of
water
or
0.5
lb
ai
per
50
shrubs.
Equipment
for
homeowner
is
hose
end
or
hand
held
pump
sprayers.
°
Pets:
Pet
care
products
are
applied
via
containers
(i.
e.,
powders
and
dusts
by
shake
can,
ready
to
use
and
pressurized
containers)
and
rubbed
in
by
hand.
Application
rate
is
made
by
the
handler.
Shampoos
also
are
applied
in
the
same
manner.
Pet
collar
application
rate
is
1
collar
per
animal
and
each
collar
contains
16
percent
ai.
Application
equipment
is
a
pet
collar.
°
Pet
bedding:
Applications
are
made
to
cover
bedding
by
dusters
or
spray
formulas
including
pressurized
sprays.
2.0
Occupational
Exposures
and
Risks
It
has
been
determined
there
is
a
potential
for
exposure
in
both
occupational
and
residential/
homeowner
scenarios
from
handling
carbaryl
products
during
the
application
process
(i.
e.,
mixer/
loaders,
applicators,
flaggers
and
mixer/
loader/
applicators)
and
from
entering
areas
previously
treated
with
carbaryl
(e.
g.,
postapplication
worker
exposure).
As
a
result,
risk
assessments
have
been
completed
for
both
occupational
handler
and
postapplication
scenarios
as
well
as
residential
handler
and
postapplication
scenarios.
This
section
includes
the
occupational
aspects
of
the
risk
assessment.
Occupational
handler
exposures
and
risks
are
addressed
in
Section
2.1:
Occupational
Handler
Exposures
and
Risks
while
occupational
post
application
worker
risks
are
presented
and
summarized
in
Section
2.2:
Occupational
Post
Application
Exposures
and
Risks.
The
calculated
risks
are
characterized
in
Section
2.3:
Occupational
Risk
Characterization.
2.1
Occupational
Handler
Exposures
and
Risks
The
Agency
uses
the
term
"Handlers"
to
describe
those
individuals
who
are
involved
in
the
pesticide
application
process.
The
agency
believes
that
there
are
distinct
job
functions
or
tasks
related
to
applications
and
that
exposures
can
vary
depending
on
the
specifics
of
each
task.
Job
requirements
(e.
g.,
amount
of
chemical
to
be
used
in
an
application),
the
kinds
of
equipment
used,
26
the
crop
or
target
being
treated,
and
the
circumstances
of
the
user
(e.
g.,
the
level
of
protection
used
by
an
applicator)
can
cause
exposure
levels
to
differ
in
a
manner
specific
to
each
application
event.
The
scenarios
that
serve
as
the
basis
for
the
risk
assessment
are
presented
in
Section
2.1.1:
Handler
Exposure
Scenarios.
The
exposure
data
and
assumptions
that
have
been
used
for
the
calculations
are
presented
in
Section
2.1.2:
Data
and
Assumptions
For
Handler
Exposure
Scenarios.
The
calculations
and
the
algorithms
that
have
been
used
for
the
noncancer
elements
of
the
risk
assessment
as
well
as
the
risk
values
are
presented
in
Section
2.1.3:
Handler
Exposure
and
NonCancer
Risk
Estimates
while
the
analogous
information
using
the
Q1*
for
cancer
estimates
are
presented
in
Section
2.1.4:
Handler
Exposure
and
Risk
Estimates
For
Cancer.
Section
2.1.5:
Summary
of
Risk
Concerns
and
Data
Gaps
For
Handlers
presents
the
overall
risk
picture
for
carbaryl.
Finally,
recommendations
are
presented
in
Section
2.1.6:
Recommendations
For
Refining
Occupational
Handler
Risk
Assessment.
2.1.1
Handler
Exposure
Scenarios
Exposure
scenarios
can
be
thought
of
as
ways
of
categorizing
the
kinds
of
exposures
that
occur
related
to
the
use
of
a
chemical.
The
use
of
scenarios
as
a
basis
for
exposure
assessment
is
very
common
as
described
in
the
U.
S.
EPA
Guidelines
For
Exposure
Assessment
(U.
S.
EPA;
Federal
Register
Volume
57,
Number
104;
May
29,
1992).
The
purpose
of
this
section
is
to
describe
the
exposure
scenarios
that
were
used
by
the
Agency
in
the
assessment
for
carbaryl
handlers
and
to
explain
how
the
scenarios
were
defined.
Information
from
the
current
labels;
use
and
usage
information;
toxicology
data;
and
exposure
data
were
all
key
components
in
the
developing
the
exposure
scenarios.
The
first
step
in
the
handler
risk
assessment
process
is
to
identify
the
kinds
of
individuals
that
are
likely
to
be
exposed
to
carbaryl
during
the
application
process.
In
order
to
do
this
in
a
consistent
manner,
the
Agency
has
developed
a
series
of
general
descriptions
for
tasks
that
are
associated
with
pesticide
applications.
Common
tasks
(as
an
example)
can
include:
preparation
of
dilute,
waterbased
spray
solutions
for
application;
transferring
or
loading
dilute
spray
solutions
into
sprayers
for
application;
and
making
applications
with
specific
types
of
equipment
such
as
a
groundboom
or
airblast
sprayer.
Tasks
associated
with
occupational
pesticide
use
(i.
e.,
for
"handlers")
can
generally
be
categorized
using
one
of
the
following
terms:
C
Occupational
Mixer/
loaders:
these
individuals
perform
tasks
in
preparation
for
an
application.
For
example,
they
would
prepare
dilute
spray
solutions
and/
or
load/
transfer
solid
materials
(e.
g.,
granulars)
or
dilute
spray
solutions
into
application
equipment
such
as
a
groundboom
tractor
or
planter
prior
to
application.
C
Occupational
Applicators:
these
individuals
operate
application
equipment
during
the
release
of
a
pesticide
product
into
the
environment.
These
individuals
can
make
applications
using
equipment
such
as
groundboom
sprayers
or
tractor
drawn
spreaders
for
granular
materials.
C
Occupational
Mixer/
loader/
applicators:
these
individuals
are
involved
in
the
entire
pesticide
application
process
(i.
e.,
they
do
all
job
functions
related
to
a
pesticide
application
27
event).
These
individuals
would
prepare
a
dilute
spray
solution
and
then
also
apply
the
solution.
The
Agency
always
considers
some
exposures
to
be
mixer/
loader/
applicator
exposures
because
of
the
equipment
used
and
the
logistics
associated
with
such
applications.
For
example,
if
one
uses
a
small
handheld
device
such
as
a
1
gallon
low
pressure
handwand
sprayer
it
is
anticipated
that
one
individual
will
mix
a
spray
solution
and
then
apply
the
solution
because
of
labor
and
logistical
considerations.
C
Occupational
Flaggers:
these
individuals
guide
aerial
applicators
during
the
release
of
a
pesticide
product
onto
an
intended
target.
Next,
assessors
must
understand
how
exposures
to
carbaryl
occur
(i.
e.,
frequency
and
duration)
and
how
the
patterns
of
these
occurrences
can
cause
the
effects
of
the
chemical
to
differ
(referred
to
as
dose
response).
Wherever
possible,
use
and
usage
data
determine
the
appropriateness
of
certain
types
of
risk
assessments
(e.
g.,
a
chronic
risk
assessment
is
not
warranted
for
a
vast
majority
of
carbaryl
uses
because
chronic
duration
exposure
patterns
do
not
occur).
Other
parameters
are
also
defined
from
use
and
usage
data
such
as
application
rates
and
application
frequency.
The
Agency
always
completes
risk
assessments
using
maximum
application
rates
for
each
scenario
because
what
is
possible
under
the
label
(the
legal
means
of
controlling
pesticide
use)
must
be
evaluated,
for
complete
stewardship,
in
order
to
ensure
there
are
no
concerns
for
each
specific
use.
Additionally,
whenever
the
Agency
has
additional
information
such
as
typical
application
rates
for
some
crops,
as
in
this
case,
it
uses
the
information
to
further
evaluate
the
overall
risks
associated
with
the
use
of
the
chemical
in
order
to
allow
for
a
more
informed
risk
management
decision.
In
this
case,
average
application
rates
(considered
to
be
the
same
as
typical
rates
for
the
purposes
of
this
assessment)
defined
in
the
recent
Quantitative
Usage
Analysis
were
available
for
some
crops
and
integrated
into
the
assessment.
A
chemical
can
produce
different
effects
based
on
how
long
a
person
is
exposed,
how
frequently
exposures
occur,
and
the
level
of
exposure.
It
is
likely
that
carbaryl
exposures
can
occur
in
a
variety
of
patterns.
The
Agency
believes
that
occupational
carbaryl
exposures
can
occur
over
a
single
day
or
up
to
weeks
at
a
time
even
though
each
crop
or
application
target
is
generally
treated
only
a
few
times
per
season.
Intermittent
exposures
over
several
weeks
are
also
anticipated.
Some
applicators
may
apply
carbaryl
over
a
period
of
weeks
because
they
need
to
cover
large
acreages,
they
may
be
custom
or
professional
applicators
that
are
completing
a
number
of
applications
within
a
region,
or
they
may
be
applying
carbaryl
over
a
period
of
several
days
(e.
g.,
a
veterinary
assistant
who
dips
dogs
periodically
over
a
period
of
several
weeks).
The
Agency
classifies
exposures
up
to
30
days
as
short
term
and
exposures
greater
than
30
days
up
to
several
months
as
intermediate
term.
The
Agency
completes
both
short
and
intermediate
term
assessments
for
occupational
scenarios
in
essentially
all
cases
because
these
kinds
of
exposures
are
likely
and
acceptable
use
and
usage
data
are
not
available
to
justify
deleting
intermediate
term
scenarios.
For
carbaryl,
the
agency
has
completed
both
short
term
assessment
and
intermediate
term
assessments
because
of
likely
extended
periods
of
exposure
in
segments
of
the
user
population.
[Note:
The
dermal
toxicity
study
NOAEL
has
been
applied
to
both
durations
and
the
NOAELs
from
the
studies
used
to
evaluate
inhalation
exposures
are
the
same
number
so
the
results
for
both
short
term
and
intermediate
term
risks
are
numerically
identical.]
Long
term
or
chronic
exposures
(essentially
every
working
day
over
a
year)
28
can
also
occur
for
some
chemicals
including
an
anticipated
small
number
of
carbaryl
users,
particularly
in
the
greenhouse
and
floriculture
industry.
These
have
been
addressed
as
appropriate.
Finally,
cancer
risks
have
also
been
calculated
using
a
amortized
lifetime
dose
(LADD)
and
linear,
low
dose
extrapolation
(i.
e.,
the
Q1*).
The
toxicity
of
chemicals
can
also
vary
based
on
the
route
of
exposure
or
how
a
chemical
enters
the
body.
For
example,
exposures
to
the
skin
can
result
in
a
different
toxic
effect
and/
or
severity
of
reaction
than
exposures
via
inhalation.
The
effects
of
a
chemical
can
also
vary
for
different
durations
of
exposure.
The
toxicology
database
for
carbaryl
indicates
that
the
Agency
consider
exposures
to
the
skin
combined
with
exposures
via
inhalation
because
the
effects
and
the
dose
levels
at
which
effects
occur
are
the
same
regardless
of
whether
it
is
deposited
on
the
skin
or
it
is
inhaled
(e.
g.,
cholinesterase
inhibition
was
the
effect
noted
for
the
inhalation
endpoint
defined
in
the
acute
neurotoxicity
study
and
for
the
dermal
endpoint
defined
in
the
21
day
dermal
toxicity
study
used
for
the
short
term
risk
assessment).
This
is
also
true
for
all
different
durations
of
exposure
as
similar
effects
were
observed
in
all
toxicity
studies
selected
as
the
source
of
the
endpoints
used
for
risk
assessment
purposes.
[Note:
For
further
information
regarding
the
toxicity
endpoints,
see
Section
1.3:
Summary
of
Toxicity
Concerns
Relating
To
Occupational/
Residential
Exposures.]
Occupational
handler
exposure
assessments
are
completed
by
the
Agency
using
different
levels
of
personal
protection.
The
Agency
typically
evaluates
all
exposures
with
a
tiered
approach.
The
lowest
tier
is
represented
by
the
baseline
exposure
scenario
followed
by
increasing
the
levels
of
personal
protection
represented
by
personal
protective
equipment
or
PPE
(e.
g.,
gloves,
extra
clothing,
and
respirators)
and
engineering
controls
(e.
g.,
closed
cabs
and
closed
loading
systems).
This
approach
is
always
used
by
the
Agency
in
order
to
be
able
to
define
label
language
using
a
riskbased
approach
and
not
based
on
generic
requirements
for
label
language.
[Note:
Current
labels
mostly
require
single
layer
clothing,
chemical
resistant
gloves,
and
no
respirator.]
In
addition,
the
minimal
level
of
adequate
protection
for
a
chemical
is
generally
considered
by
the
Agency
to
be
the
most
practical
option
for
risk
reduction
(i.
e.,
over
burdensome
risk
mitigation
measures
are
not
considered
a
practical
alternative).
The
levels
of
protection
that
formed
the
basis
for
the
calculations
in
this
assessment
include
(which
were
combined
to
obtain
8
different
scenarios):
C
Baseline:
Represents
typical
work
clothing
or
a
long
sleeved
shirt
and
long
pants
with
no
respiratory
protection.
No
chemical
resistant
gloves
are
included
in
this
scenario.
C
Minimum
Personal
Protective
Equipment
(PPE):
Represents
the
baseline
scenario
with
the
use
of
chemical
resistant
gloves
and
a
dust/
mist
respirator
with
a
protection
factor
of
5.
C
Maximum
Personal
Protective
Equipment
(PPE):
Represents
the
baseline
scenario
with
the
use
of
an
additional
layer
of
clothing
(e.
g.,
a
pair
of
coveralls),
chemical
resistant
gloves,
and
an
air
purifying
respirator
with
a
protection
factor
of
10.
C
Engineering
Controls:
Represents
the
use
of
an
appropriate
engineering
control
such
as
a
closed
tractor
cab
or
closed
loading
system
for
granulars
or
liquids.
Engineering
controls
are
not
applicable
to
handheld
application
methods
which
have
no
known
devices
that
can
be
used
to
routinely
lower
the
exposures
for
these
methods.
29
It
has
been
determined
that
exposure
to
pesticide
handlers
is
likely
during
the
occupational
use
of
carbaryl
in
a
variety
of
environments
including
agriculture,
commercial/
industrial
premises,
and
in
residential
environments.
The
anticipated
use
patterns
and
current
labeling
indicate
28
major
occupational
exposure
scenarios
based
on
the
types
of
equipment
and
techniques
that
can
potentially
be
used
to
make
carbaryl
applications.
The
quantitative
exposure/
risk
assessment
developed
for
occupational
handlers
is
based
on
these
scenarios.
[Note:
The
scenario
numbers
correspond
to
the
tables
of
risk
calculations
included
in
the
occupational
risk
calculation
aspects
of
the
appendices.]
Mixing/
Loading
(1a)
Dry
Flowable
for
Aerial/
Chemigation
in
Agriculture;
(1b)
Dry
Flowable
for
Airblast;
(1c)
Dry
Flowable
for
Groundboom;
(1d)
Dry
Flowable
for
High
Pressure
Handwand
and
Right
of
Way
Sprayers;
(1e)
Dry
Flowable
for
LCO
Applications;
(1f)
Dry
Flowable
for
Aerial
Wide
Area
Uses;
(2a)
Granular
for
Aerial;
(2b)
Granular
for
Broadcast
Spreader;
(3a)
Liquids
for
Aerial/
Chemigation;
(3b)
Liquids
for
Airblast;
(3c)
Liquids
for
Groundboom;
(3d)
Liquids
for
High
Pressure
Handwand
and
Right
of
Way
Sprayers;
(3e)
Liquids
for
LCO
Applications;
(3f)
Liquids
for
Aerial
Wide
Area
Uses;
(3g)
Liquids
for
Ground
Wide
Area
Uses;
(4a)
Wettable
Powder
for
Aerial/
Chemigation;
(4b)
Wettable
Powder
for
Airblast;
(4c)
Wettable
Powder
for
Groundboom;
(4d)
Wettable
Powder
for
High
Pressure
Handwand
and
Right
of
Way
Sprayers;
(4e)
Wettable
Powder
for
LCO
Applications;
(4f)
Wettable
Powder
for
Aerial
Wide
Area
Uses;
Applicator:
(5a)
Aerial/
Liquid
Application;
(5b)
Aerial/
Liquid
Wide
Area
Application;
(5c)
Aerial/
Granular
Application;
(6a)
Airblast
Application;
(6b)
Wide
Area
Ground
Fogger
(Airblast
as
surrogate);
(7)
Groundboom
Application;
(8)
Solid
Broadcast
Spreader
Application;
(9)
Aerosol
Can
Application;
(10)
Trigger
Sprayer
(RTU)
Application;
(11)
Right
of
Way
Sprayer
Application;
(12)
High
Pressure
Handwand
Application;
30
(13)
Veterinary
Technician/
Animal
Groomer
Liquid
Application;
(14)
Veterinary
Technician/
Animal
Groomer
Dust
Application;
(15)
Granulars/
Bait
and
Pellets
Dispersed
by
Hand;
(16)
Granulars/
Bait
and
Pellets
Dispersed
with
Spoon;
Mixer/
Loader/
Applicator:
(17)
Low
Pressure/
High
Volume
Turfgun
Application;
(18a)
Wettable
powder,
Low
pressure
handwand;
(18b)
Liquid:
Low
Pressure
Handwand;
(19)
Backpack;
(20)
Granular
Belly
Grinder;
(21)
Push
type
Granular
Spreader;
(22)
Handheld
Fogger;
(23)
Powered
Backpack;
(24)
Granular
Backpack;
(25)
Tree
Injection;
(26)
Drenching/
Dipping
Seedlings
For
Propagation;
(27)
Sprinkler
Can;
Flaggers:
(28a)
Flagging
For
Liquid
Sprays;
and
(28b)
Flagging
For
Granular
Applications.
2.1.2
Data
and
Assumptions
For
Handler
Exposure
Scenarios
A
series
of
assumptions
and
exposure
factors
served
as
the
basis
for
completing
the
occupational
handler
risk
assessments.
Each
assumption
and
factor
is
detailed
below
on
an
individual
basis.
In
addition
to
these
values,
exposure
values
were
used
to
calculate
risk
estimates.
Mostly,
these
values
were
taken
from
the
Pesticide
Handlers
Exposure
Database
(PHED).
In
other
cases,
chemical
specific
data
were
submitted
to
support
the
reregistration
of
carbaryl.
Both
PHED
and
the
individual
studies
are
presented
below.
31
The
assumptions
and
factors
used
in
the
risk
calculations
include:
C
Carbaryl
is
one
of
the
most
widely
used
pesticide
chemicals.
It
has
an
extraordinary
number
of
use
patterns
that
are
impossible
to
completely
capture
in
this
document.
As
such,
the
Agency
has
patterned
this
risk
assessment
on
a
series
of
likely
representative
scenarios
that
are
believed
by
the
Agency
to
represent
the
vast
majority
of
carbaryl
uses.
Refinements
to
the
assessment
will
be
made
as
more
detailed
information
about
carbaryl
use
patterns
become
available.
C
The
carbaryl
80
S
label
EPA
Reg
264
316
has
a
24(
c)
label
(SLN
WA
900013)
that
allows
application
to
oyster
beds
to
control
ghost
and
mud
shrimp.
The
application
rate
is
8
lb
ai/
acre
based
on
information
from
Bob
Merkel
of
the
Washington
State
Department
of
Agriculture
(WSDA)
[contained
in
email
from
CRM
Anthony
Britten
of
1/
3/
02].
WSDA
information
also
indicates
that
applications
are
completed
with
helicopters
over
a
3
day
period
in
July
and
that
approximately
800
acres
are
treated
usually
with
3
aircraft.
Beds
are
treated
with
10
gallons
of
spray
solution
per
acre
at
a
concentration
of
0.8
lb
ai/
gallon.
With
this
information,
the
Agency
calculated
that
approximately
89
acres
would
be
treated
per
day
by
each
helicopter
and
that
711
lb
ai
would
also
be
used.
The
Agency
did
not
calculate
risks
specifically
for
this
scenario.
However,
the
Agency
considered
a
wide
range
of
aerial
application
scenarios
in
this
assessment.
For
all
formulations
and
for
pilots,
the
vegetable
scenario
based
on
2
lb
ai/
acre
and
350
acres
treated
per
day
(i.
e.,
700
lb
ai
applied
per
day)
yields
essentially
the
same
risk
numbers
that
would
be
associated
with
treating
oyster
beds.
As
a
result,
please
refer
to
the
aerial
vegetable
scenarios
to
obtain
risk
estimates
for
treating
oyster
beds.
C
Average
body
weight
of
an
adult
handler
is
70
kg
because
the
toxicity
endpoint
values
used
for
the
assessments
are
appropriate
for
average
adult
body
weight
representing
the
general
population.
This
is
the
case
because
none
of
the
effects
identified
in
the
selected
toxicity
studies
were
sex
specific
(i.
e.,
NOAELs
selected
by
HIARC
were
the
same
for
males
and
females).
C
All
analyses
were
completed
using
chemical
specific
exposure
data
or
data
that
were
deemed
to
be
a
source
of
acceptable
surrogate
exposure
data
for
the
scenario
in
question.
Several
handler
assessments
were
completed
using
"low
quality"
PHED
data
due
to
the
lack
of
a
more
acceptable
dataset.
Additionally,
in
some
cases,
no
empirical
data
were
available
for
the
scenario
but
an
exposure
assessment
approach
was
developed
based
on
an
approach
outlined
in
the
SOPs
For
Residential
Exposure
Assessment.
In
these
cases,
the
assumptions
and
approached
included
in
the
SOPs
served
as
the
basis
for
the
assessment
(e.
g.,
some
pet
uses).
The
PHED
unit
exposure
values
range
between
the
geometric
mean
and
the
median
of
the
available
exposure
data.
Factors
derived
from
the
SOPs
For
Residential
Exposure
Assessment
are
generally
considered
to
be
conservative.
When
data
from
other
studies
were
used,
the
appropriate
statistical
measure
of
central
tendency
was
used
(see
each
study
summary
below
for
data
descriptor).
32
C
Several
generic
protection
factors
were
used
to
calculate
handler
exposures.
The
protection
factors
used
for
clothing
layers
(i.
e.,
50%)
and
gloves
(90%)
have
not
been
completely
evaluated
by
the
Agency.
Additionally,
the
Agency
uses
a
98%
reduction
factor
to
estimate
exposures
that
involve
the
use
of
engineering
controls.
There
is
an
ongoing
project
through
NAFTA
to
address
the
issue
of
protection
factors
(a
draft
document
assessing
protection
factors
using
PHED
has
been
completed).
The
results
of
this
effort
show
that
the
protection
factors
being
currently
used
by
the
Agency
are
within
those
predicted
in
the
analysis.
The
values
used
for
respiratory
protection
(i.
e.,
PF
5
or
PF
10)
are
based
on
the
NIOSH
Respirator
Decision
Logic.
C
Exposure
factors
used
to
calculate
daily
exposures
to
handlers
are
based
on
applicable
data
if
available.
For
lack
of
appropriate
data,
values
from
a
scenario
deemed
similar
enough
by
the
assessor
might
be
used.
As
a
example,
mixer/
loader/
applicator
data
for
hose
end
sprayers
were
used
to
assess
sprinkler
can
applications.
The
nature
of
these
application
methods
are
believed
to
be
similar
enough
to
bridge
the
data.
There
are
other
instances
where
the
Agency
has
bridged
specific
data
to
represent
other
scenarios.
C
Separate
short
term,
intermediate
term,
and
chronic
risk
assessments
were
completed
for
the
noncancer
endpoints
based
on
the
toxicity
endpoints
that
were
identified.
The
Agency
believes
that
there
are
exposure
scenarios
that
fit
each
of
these
categories.
All
noncancer
scenarios
are
expected
to
be
short
or
intermediate
term
in
nature.
The
Agency
only
anticipates
a
limited
number
of
scenarios
that
are
chronic
in
nature
which
are
included
in
the
greenhouse
and
ornamental
industry.
The
Agency
also
calculated
cancer
risks
for
private
growers
(i.
e.,
those
growers
who
would
treat
their
own
fields)
and
for
more
frequent
carbaryl
users
such
as
a
commercial
applicator.
The
range
in
the
cancer
risk
assessments
is
intended
to
address
the
large
population
of
growers
who
likely
complete
their
own
applications
but
also
to
address
likely
smaller,
more
highly
exposed
commercial
applications.
The
Agency
has
used
a
value
of
30
application
events
per
year
for
all
commercial
applicator
scenarios
and
10
days
per
year
to
account
for
private
growers
(i.
e.,
1/
3rd
of
the
analogous
professional
job
function,
this
is
also
used
for
the
postapplication
risk
assessment).
These
values
are
supported
by
the
data
included
in
the
University
of
California
studies
of
seasonal
labor
in
California
and
the
recent
Department
of
Labor
National
Agricultural
Worker
Survey
(NAWS).
C
The
exposure
duration
(i.
e.,
years
per
lifetime)
values
used
by
the
Agency
in
the
cancer
risk
assessment
are
consistent
with
those
used
for
other
chemicals
(i.
e.,
35
working
years
and
70
year
lifetime).
33
C
In
many
scenarios
it
is
likely
that
a
grower
would
mix,
load,
and
apply
chemicals
all
in
one
day
because
of
limited
labor,
efficiency,
or
many
other
reasons.
In
most
cases,
however,
the
Agency
considers
mixing/
loading,
and
application
as
separate
job
functions.
This
is
done
primarily
due
to
a
lack
of
data
that
allows
additivity
between
tasks
to
be
appropriately
assessed.
Also,
this
approach
allows
for
more
flexibility
in
the
risk
management
process.
For
example,
if
a
closed
loading
system
might
be
required
for
mixer/
loaders
but
engineering
controls
might
not
be
required
to
reduce
applicator
exposures.
If
combined
exposure
estimates
were
considered,
engineering
controls
might
have
been
required
for
both
tasks.
C
The
Agency
has
evaluated
scenarios
that
may
be
limited
in
nature
such
as
flagging
during
aerial
applications
because
engineering
controls
(i.
e.,
Global
Positioning
Satellite
technology)
are
now
predominantly
used
as
indicated
by
the
1998
National
Agricultural
Aviation
Association
(NAAA)
survey
of
their
membership.
It
appears,
however,
flaggers
are
still
used
in
approximately
10
to
15
percent
of
aerial
application
operations.
In
cases
like
these,
the
Agency
strongly
encourages
the
use
of
the
engineering
control
system
but
will
continue
to
evaluate
risks
for
flaggers
and
any
other
population
where
a
clear
exposure
pathway
exists
until
the
potential
for
exposure
is
eliminated.
C
The
Agency
always
considers
the
maximum
application
rates
allowed
by
labels
in
its
risk
assessments
in
order
to
be
able
to
consider
what
is
legally
possible
based
on
the
label.
If
additional
information
such
as
average
or
typical
rates
are
available,
these
values
are
used
as
well
in
order
to
allow
risk
managers
to
make
a
more
informed
risk
management
decision.
Average
application
rates
were
available
from
the
SMART
meeting
and
BEAD's
QUA.
These
data
indicate
that
in
most
cases,
average
application
rates
differ
from
maximum
application
rates
on
average
by
a
factor
of
two.
For
example,
when
interpreting
the
results
of
the
cancer
assessment,
the
small
differences
generally
seen
in
the
available
rates
should
be
considered
along
with
the
overall
magnitude
of
the
cancer
risk
results.
However,
it
should
be
noted
that
because
there
appears
to
be
little
difference
between
the
typical
and
maximum
application
rates,
overall
risk
results
are
not
expected
to
be
sensitive
to
changes
in
this
parameter.
C
The
average
occupational
workday
is
assumed
to
be
8
hours.
The
daily
areas
to
be
treated
were
defined
for
each
handler
scenario
(in
appropriate
units)
by
determining
the
amount
that
can
be
reasonably
treated
in
a
single
day
(e.
g.
acres,
animals).
The
factors
used
for
the
carbaryl
assessment
are
the
same
as
those
detailed
in
the
Health
Effects
Division
Science
Advisory
Committee
on
Exposure
Policy
9:
Standard
Values
for
Daily
Acres
Treated
in
Agriculture
which
was
completed
on
July
5,
2000.
The
following
daily
volumes
handled
and
acres,
excerpted
from
the
policy,
to
be
treated
in
each
occupational
scenario
include:
C
Aerial
applications:
1200
acres
for
large
field
crops
and
forest
treatments,
350
acres
for
other
field
crops,
and
7500
acres
for
mosquito
control
adulticide
applications;
C
Groundboom:
200
acres
for
large
field
crops
(e.
g.,
wheat
and
corn),
80
acres
treated
for
other
field
crop
groundboom
applications,
and
40
acres
on
golf
course
turf;
C
Airblast:
40
acres
treated
for
agricultural
applications;
34
C
Ground
fogger:
3000
acres
for
mosquito
control
(airblast
as
surrogate);
C
8
pet
animals
treated
per
day
for
veterinary
and
professional
groomer
uses;
C
1000
gallons
of
spray
solution
prepared
when
mixing/
loading
liquids
for
high
pressure
handwand
application
or
making
the
application;
C
40
gallons
when
mixing/
loading/
applying
liquids
with
a
backpack
sprayer
or
a
low
pressure
handwand
sprayer;
C
10
mounds
per
day
treated
for
fire
ant
applications.
[Note:
The
veterinary
and
fireant
treatments
are
not
included
in
the
policy
but
represent
values
that
have
been
used
by
the
Agency
in
previous
assessments.
Some
carbaryl
use
patterns
may
not
be
summarized
above,
refer
to
Policy
9
for
further
information.]
C
For
direct
pet
animal
treatments,
Agency
policy
outlined
in
the
Residential
SOPs,
was
used
to
define
the
amount
of
chemical
applied
in
animal
treatments.
For
pet
treatments,
the
SOPs
prescribe
that
½
of
a
container
is
used
to
treat
each
animal.
Dusts
and
liquid
shampoos
for
carbaryl
are
available
in
a
6
ounce
bottle
(0.5%
solution)
and
a
4
lb
container
(10%
dust).
C
Currently
the
Agency
has
no
exposure
monitoring
data
on
dust
applications
to
crops
in
agriculture.
There
are
other
data
gaps
that
have
been
identified
for
carbaryl
applications.
Each
is
identified
in
the
calculation
tables
and
is
also
noted
in
the
summary
of
risk
calculations.
C
Ultra
low
volume
applications
for
uses
such
as
mosquito
control
adulticides
were
considered
using
a
large
acreage
estimate
to
aerial
applicators.
The
mosquito
adulticide
uses
that
were
evaluated
in
the
same
manner
as
other
chemicals
used
for
that
purpose
(e.
g.,
the
same
acreage
estimates
were
used
as
for
other
chemicals
like
fenthion
and
naled).
C
The
impact
of
using
large
area
(i.
e.,
acreage)
estimates
should
be
considered
when
interpreting
the
results
such
as
with
the
scenarios
intended
to
address
wide
area
treatments.
For
wide
area
treatments,
the
Agency
considered
large
acreage
aerial
applications
but
did
not
quantitatively
consider
ground/
truck
fogging
which
is
another
likely
application
method.
In
the
past,
the
Agency
has
used
airblast
application
exposure
data
to
address
this
scenario.
However,
already
given
the
complexity
of
the
handler
risk
assessment
and
the
rangefinder
nature
of
using
airblast
data,
the
Agency
has
not
completed
these
calculations.
A
qualitative
estimate
of
risks
can
be
made
by
considering
the
airblast
results
for
agriculture
and
adjusting
the
risk
values
as
appropriate
for
acres
treated
(3000
acres/
day
for
ground
foggers)
and
application
rate.
The
Agency
uses
a
concept
known
as
unit
exposure
as
the
basis
for
the
scenarios
used
to
assess
handler
exposures
to
pesticides.
Unit
exposures
numerically
represent
the
exposures
one
would
receive
related
to
an
application.
They
are
generally
presented
as
(mg
active
ingredient
exposure/
pounds
of
active
ingredient
handled).
The
Agency
has
developed
a
series
of
unit
exposures
that
are
unique
for
each
scenario
typically
considered
in
our
assessments
(i.
e.,
there
are
different
unit
exposures
for
different
types
of
application
equipment;
job
functions;
and
levels
of
protection).
The
unit
exposure
concept
has
been
established
in
the
scientific
literature
and
also
35
through
various
exposure
monitoring
guidelines
published
by
the
U.
S.
EPA
and
international
organizations
such
as
Health
Canada
and
OECD
(Organization
For
Economic
Cooperation
and
Development).
The
concept
of
unit
exposures
can
be
illustrated
by
the
following
example.
If
an
individual
makes
an
application
using
a
groundboom
sprayer
with
either
10
pounds
of
chemical
A
or
10
pounds
of
chemical
B
using
the
same
application
equipment
and
protective
measures,
the
exposures
to
chemicals
A
and
B
would
be
similar.
The
unit
exposure
in
both
cases
would
be
1/
10th
of
the
total
exposure
(measured
in
milligrams)
received
during
the
application
of
either
chemical
A
or
chemical
B
(i.
e.,
milligrams
on
the
skin
after
applying
10
pounds
of
active
ingredient
divided
by
10
pounds
of
active
ingredient
applied).
The
unit
exposure
values
that
were
used
in
this
assessment
were
based
on
one
carbarylspecific
occupational
handler
exposure
monitoring
study
during
professional
dog
grooming,
three
other
studies
which
were
used
as
sources
of
surrogate
exposure
information
that
are
not
currently
included
in
the
Pesticide
Handler
Exposure
Database
(PHED)
Version
1.1
August
1998,
and
PHED
itself.
A
brief
summary
of
these
studies
is
provided
below
in
this
section.
Along
with
these
data,
unit
exposures
from
PHED
were
used
to
complete
remaining
aspects
of
this
risk
assessment.
Each
is
discussed
and
summarized
below.
Occupational
Handler
Exposure
Studies:
A
total
of
five
studies
are
described
in
this
section.
One
study
monitored
carbaryl
use
during
professional
dog
grooming
activities.
The
other
studies
were
not
completed
with
carbaryl
but
were
completed
with
other
active
ingredients
and
used
as
a
source
of
surrogate
exposure
information
for
various
carbaryl
use
patterns.
Each
study
can
be
identified
with
the
following
information.
A
summary
of
each
is
also
provided
below.
°"
Dermal
Exposure
and
Inhalation
Exposure
to
Carbaryl
by
Commercial
Pet
Groomers
During
Applications
of
Adams
™
Carbaryl
Shampoo."
EPA
MRID
446584
01,
September
1998
Report
dated
August
10,
1998;
Author;
Thomas
C.
Mester,
Ph.
D.
Sponsor:
Pfizer
Animal
Health.
°"
Worker
Exposure
Study
During
Application
In
Banana
Plantation
With
Temik
10G,
RP
Study
SA
98337,
EPA
MRID
451672
01,
Vol.
3
of
4"
EPA
MRID
451672
01;
November
1999
Report;
Author:
Michel
Urtizberea;
Sponsor:
Aventis
Crop
Protection;
EPA
DER
Completed
on
10/
17/
00
(DP
Barcode
D267546).
°"
Worker
Exposure
Study
During
Application
Of
Regent
20GR
In
Banana
Plantation,
(RP
Study
94/
136
Amended,
EPA
MRID
452507
01,
Vol.
4
of
4,
Analytical
Lab.
CP/
Man/
ENH/
338/
95/
0072)"
EPA
MRID
452507
02;
June
1996
Report;
Author:
P.
G.
Pontal;
Sponsor:
Aventis
Crop
Protection;
EPA
DER
Completed
on
1/
05/
01
(DP
Barcode
270065).
36
°"
Exposure
of
Applicators
to
Propoxur
During
Trigger
Pump
Spray
Applications
of
a
Liquid
Product
"
EPA
MRID
410547
01;
November
1,
1988;
Author:
R.
D.
Knarr,
Ph.
D.,
CIH;
Sponsor:
Bayer
Corporation;
EPA
review
(9/
29/
89)
by
Versar,
Inc.
for
PHED
purposes
under
Contract
68
02
4254,
Task
220.
°"
Integrated
Report
For
Evaluation
of
Potential
Exposures
To
Homeowners
and
Professional
Lawncare
Operators
Mixing,
Loading,
and
Applying
Granular
And
Liquid
Pesticides
To
Residential
Lawns
"
EPA
MRID
449722
01;
October
10,
1999;
Author:
Dennis
R.
Klonne,
Ph.
D.;
Sponsor:
Outdoor
Residential
Exposure
Task
Force;
EPA
Review
by
Gary
Bangs
(April
30,
2001).
[Note
to
Chemical
Review
Manager:
There
are
no
data
compensation
issues
associated
with
the
use
of
non
ORETF
data
included
in
MRIDs
451672
01
and
452507
01
as
these
studies
were
sponsored
and
submitted
by
the
Aventis
Corporation
and
the
propoxur
trigger
sprayer
study
has
a
signed
PHED
data
waiver
but
just
has
not
been
included
into
PHED
at
this
time.
Appendix
B
contains
the
data
excerpted
from
MRID
446585
01
in
various
tables
which
is
a
carbaryl
specific
study
recently
completed
by
the
Aventis
Corporation.
Data
from
the
other
referenced
studies
are
not
included
in
Appendix
B
because
separate
reviews
exist
for
each
which
can
be
independently
referenced.
Some
of
the
handler
exposure
data
used
in
this
assessment
are
from
the
Outdoor
Residential
Exposure
Task
Force
(ORETF).
There
is
also
no
data
compensation
issue
associated
with
the
use
of
the
ORETF
data
in
the
carbaryl
risk
assessment
because
the
Aventis
Corporation,
the
registrant
for
carbaryl,
is
a
member
of
the
ORETF.
The
task
force
recently
submitted
proprietary
data
to
the
Agency
on
hose
end
sprayers,
push
type
granular
spreaders,
and
handgun
sprayers
(MRID
#
44972201).
The
ORETF
data
were
used
in
this
assessment
in
place
of
PHED
data.
The
ORETF
data
were
designed
to
replace
the
present
PHED
data
with
higher
confidence,
higher
quality
data
that
contains
more
replicates
than
the
PHED
data
for
those
scenarios.
Finally,
the
Agency
identified
several
occupational
exposure
studies
from
the
literature
by
investigators
such
as
Popendorf
and
Wolfe.
These
data
have
not
been
used
by
the
Agency
quantitatively
in
this
assessment
because
of
several
issues
but
were
qualitatively
considered
and
also
used
to
confirm
the
currently
used
exposure
data.]
MRID
446584
01
(carbaryl
specific
dog
groomer
data):
The
data
collected
reflect
the
dermal
and
respiratory
exposure
of
commercial
pet
groomers
applying
the
end
use
product,
Adams®
Carbaryl
Flea
and
Tick
Shampoo
containing
0.50
percent
carbaryl.
These
data
meet
most
of
the
criteria
specified
in
Series
875
Occupational
and
Residential
Exposure
Test
Guidelines.
The
data
are
of
sufficient
scientific
quality
to
be
used
in
the
reregistration
of
carbaryl.
The
protocol
was
reviewed
by
the
then
Occupational
and
Residential
Exposure
Branch
of
the
Health
Effects
Division.
The
protocol
was
accepted
as
written
with
the
stipulation
that
protective
latex
gloves
not
be
worn
by
groomers
because
"this
protocol
was
required
as
a
worst
case
estimate
of
exposure.
Therefore,
the
use
of
gloves
in
this
study
needs
to
be
deleted"
(From
George
Tompkins
to
Michael
Metzger,
dated
November
26,
1996).
In
this
study,
applications
of
Adams®
Carbaryl
Flea
and
Tick
Shampoo
were
made
by
professional
pet
groomers
to
8
dogs
at
2
sites
in
Georgia.
A
total
of
16
replicates
were
monitored
for
dermal
and
inhalation
exposure.
Eight
dogs
of
various
sizes
and
hair
lengths
were
shampooed
during
each
replicate.
Dermal
exposure
was
monitored
with
face
and
neck
swabs,
100
37
percent
cotton
union
suit
dosimeter
worn
underneath
a
short
sleeved
t
shirt,
long
pants
and
a
65/
35
polyester
cotton
long
sleeved
smock
(i.
e.,
represents
a
short
sleeved
shirt
under
a
long
sleeved
coat/
smock).
Hand
exposure
was
quantified
using
handwash
rinses
(no
protective
gloves
were
worn).
Inhalation
exposure
was
monitored
using
personal
air
pumps
with
XAD2
resin
tubes.
Between
373.3
to
3719.95
mg
carbaryl
(average
use
was
1360
mg
ai)
was
used
to
shampoo
8
dogs.
According
to
label
directions,
the
application
rate
is
a
subjective
determination
by
the
individual
groomers
based
on
amount
needed
to
create
the
desired
lather.
The
dogs
were
wetted,
shampooed
to
a
lather
(lather
remained
on
dogs
for
5
minutes)
and
rinsed.
It
is
not
clear
how
many
or
which
of
the
dogs
got
further
post
shampoo
attention
such
as
grooming
or
drying.
After
completing
8
dog
shampoos
the
dosimeters
were
collected.
Face/
neck
swabs
and
2
hand
rinses
were
performed
along
with
collection
of
the
100
percent
cotton
union
suit.
Only
wholebody
dosimeter
values
were
adjusted
for
field
recovery
(87
percent).
No
other
samples
were
corrected
for
recovery
as
the
field
and
laboratory
recoveries
generally
were
>90
percent.
Dermal
exposures
ranged
between
0.88
mg
and
17
mg
ai
and
inhalation
exposures
range
between
0.05
µg
(non
detect)
and
1.96
µg
ai.
The
limit
of
detection
(LOD)
was
0.010
µg/
ml.
The
limit
of
quantitation
(LOQ)
was
1
µg
per
whole
body
dosimeter,
0.10
µg/
ml
for
50
ml
hand
wash
aliquot,
0.10
µg
per
facial
wipe,
0.10
µg
per
resin
tube,
and
0.10
µg
for
glass
fiber
filter/
support
pad.
Table
5
contains
the
results
which
have
been
normalized
based
on
each
of
the
following
factors:
°
mg
ai
exposed
per
lb
ai
handled;
°
ai
exposed
per
hour,
and
°
mg
ai
per
lb
dog
shampooed.
°
The
geometric
mean
of
the
normalized
numbers
was
used
in
reregistration
calculations
because
it
is
a
measure
of
central
tendency.
Even
though
the
study
protocol
was
approved
prior
to
completion
of
the
field
work,
the
following
factors
should
be
considered
when
interpreting
these
results.
In
this
task,
direct
contact
of
the
dipping
solution
with
the
hands
represents
a
major
potential
source
of
exposure.
Therefore,
obtaining
accurate
hand
exposure
estimates
is
critical
in
defining
the
risks
for
this
use.
The
study
measured
the
amount
of
carbaryl
left
on
the
hands
after
8
shampoos
and
rinses
using
an
aqueous
handwash
method.
Shampoo
was
applied,
a
lather
was
created
and
rinsed
off
with
a
large
degree
of
hand
contact
with
the
shampoo
and
water
stream.
Carbaryl
repeatedly
contacted
the
hand
for
the
duration
of
the
grooming
and
some
was
removed
during
the
rinsing
of
each
dog.
Because
of
this
potential
flux
of
residues
off
and
on
the
groomer's
hands
and
the
presence
of
surfactants
which
may
impact
dermal
absorption
levels,
the
handwash
method
may
underestimate
exposures.
This
study
should
not
be
used
for
residential
exposure
assessments
because
protective
clothing
(i.
e.,
smock
and
long
pants)
were
worn
over
the
whole
body
dosimeters
and
adjusting
the
data
using
negative
protection
factors
which
is
generally
not
considered
appropriate.
38
Table
5:
Unit
Exposure
Values
Obtained
From
Professional
Dog
Groomer
Study
(MRID
446584
01)
Dermal
Inhalation
Unit
Arithmetic
Mean
Geometric
Mean
Median
Unit
Arithmetic
Mean
Geometric
Mean
Median
mg
ai
/
lb
ai
handled
1900
1800
1800
µg
ai
/
lb
ai
handled
24
12
19
mg
ai
/
hour
application
1.6
1.
1
1.1
µg
ai
/
hour
application
0.20
0.96
0.21
mg
ai
/
lb
of
dog
treated
0.18
0.13
0.14
µg
ai
/
lb
of
dog
treated
0.020
0.011
0.020
Appendix
B
contains
the
data
excerpted
from
MRID
446585
01.
Data
from
none
of
the
other
studies
are
included
in
Appendix
B
because
separate
reviews
exist
for
each
of
the
other
studies
which
can
be
independently
referenced.
EPA
MRID
45167201
(Temik
granular
backpack
study):
A
total
of
12
mixer/
loader/
applicator
events
during
granular
backpack
(i.
e.,
a
specialized
device
manufactured
by
Swissmex
Rapid)
application
to
bananas
were
monitored
during
August
of
1998
on
the
island
of
Martinique
which
is
in
the
French
West
Indies.
Weather
was
typical
of
the
application
season
in
that
it
was
hot,
humid,
and
rainy
at
points.
Monitoring
was
completed
using
whole
body
dosimeters,
handwashes,
facial
wipes,
and
personal
sampling
pumps
equipped
with
XAD
resin/
filter
combination
samplers.
Temik
10G
was
supplied
in
22
pound
boxes
which
was
loaded
directly
into
the
backpack
devices
(i.
e.,
4
to
8
boxes
were
used
per
replicate).
The
application
rate
for
aldicarb
used
in
this
study
is
20
grams
of
Temik
10G
(i.
e.,
2
grams
ai/
plant)
which
is
equivalent
to
about
3.56
lb
ai/
acre
at
approximately
2000
plants
per
acre.
The
numbers
of
acres
treated
ranged
from
approximately
2.5
to
5
acres.
The
pounds
of
active
ingredient
handled
ranged
from
8.8
up
to
17.6
per
replicate.
Each
applicator
wore
the
whole
body
dosimeters
covered
by
a
cotton
coverall,
Tyvek
gloves
supplied
with
the
Temik
10G
formulation,
and
an
apron
on
their
backs
between
their
backs
and
the
backpack
applicator.
The
Tyvek
gloves
were
changed
with
each
box
of
Temik
10G
used.
In
many
instances,
the
gloves
were
compromised
because
they
were
ripped.
In
one
case,
the
gloves
filled
with
rainwater.
In
many
other
cases,
when
the
whole
body
dosimeters
were
removed,
they
were
found
to
be
wet
and
muddy.
Analysis
of
aldicarb
and
its
sulfoxide
and
sulfone
degradates
was
completed.
The
residue
levels
were
added
together
to
obtain
total
exposure
levels.
The
limits
of
quantification
(LOQ)
were
1.0
µg
per
sample
for
the
whole
body
dosimeters
and
handwashes
(600
mL
volume).
The
LOQ
for
the
facial
wipes
was
0.10
µg
per
sample
and
0.050
0.10
µg
per
sample
for
the
air
filters.
Field
and
laboratory
recovery
data
were
generated
for
all
media
for
all
residues
measured
(i.
e.,
parent
and
metabolites).
Field
recovery
data
were
generated
in
a
manner
that
addressed
field
sampling,
field
storage,
transport,
laboratory
storage,
and
analysis.
Residues
were
corrected
for
the
overall
average
field
recovery
for
each
residue/
matrix
combination.
Generally,
recovery
was
adequate
for
all
media/
residue
combinations.
If
the
PHED
grading
criteria
are
applied,
all
residue/
matrix
combinations
(except
facial
wipes
with
sulfone
residues)
have
at
least
grade
"B"
data
and
in
many
cases
the
data
meet
the
grade
"A"
criteria.
The
grade
"B"
criteria
require
laboratory
recovery
data
with
an
average
of
at
least
80
percent
and
a
coefficient
of
variation
of
25
or
less
39
accompanied
with
field
recoveries
that
are
at
least
50
percent
but
not
exceeding
120
percent.
The
grade
"A"
criteria
require
laboratory
recovery
data
with
an
average
of
at
least
90
percent
and
a
coefficient
of
variation
of
15
or
less
accompanied
with
field
recoveries
that
are
at
least
70
percent
but
not
exceeding
120
percent.
Unit
exposure
values
were
calculated
using
the
data
from
the
study
and
a
commercial
spreadsheet
program
(Table
6).
The
exposures
that
were
calculated
were
normalized
by
the
amount
of
chemical
used,
the
duration
of
the
application
interval,
and
by
the
body
weight
of
the
individual
applicators.
For
each
calculation,
the
arithmetic
mean,
geometric
mean,
and
various
percentiles
were
calculated.
No
analyses
were
completed
with
these
data
to
ascertain
the
exact
type
of
distribution.
The
Agency
typically
uses
the
best
fit
values
from
the
Pesticide
Handlers
Exposure
Database
which
are
representations
of
the
central
tendency.
Considering
the
standard
practice,
the
Agency
will
use
the
geometric
mean
for
risk
assessment
purposes.
The
other
values
are
presented
for
comparative
purposes.
Table
6:
Unit
Exposure
Values
Obtained
From
Granular
Backpack
Application
Study
(MRID
451672
01)
Type
(mg
exp./
lb
ai
handled)
(mg
exp./
hour)
(mg
exp./
kg
body
weight/
day)
Dermal
Inhalation
Dermal
Inhalation
Dermal
Inhalation
Arith.
Mean
0.1391
0.0046
0.5473
0.0179
0.0585
0.0018
Geo.
Mean
0.0995
0.0042
0.3979
0.0169
0.0409
0.0017
25th
%tile
0.0474
0.0031
0.2511
0.0134
0.0220
0.0015
75th
%tile
0.1691
0.0062
0.7436
0.0229
0.0765
0.0023
90th
%tile
0.2217
0.0068
0.8489
0.0264
0.0947
0.0027
95th
%tile
0.3510
0.0076
1.2119
0.0282
0.1390
0.0028
99th
%tile
0.4722
0.0083
1.5594
0.0298
0.1805
0.0030
EPA
MRID
452507
01
(Fipronil
Spoon
Application
Study):
A
total
of
18
mixer/
loader/
applicator
events
during
granular
backpack
(i.
e.,
a
specialized
device
manufactured
by
Horstine
Farmery)
or
spoon
application
to
bananas
were
monitored
during
applications
on
three
different
days
in
June,
1994
on
the
same
banana
plantation
in
Cameroon.
[Note:
Only
the
spoon
application
data
included
in
this
study
are
used
in
the
carbaryl
risk
assessment
as
backpack
granular
applications
have
been
assessed
using
the
data
presented
above.]
The
18
replicates
were
distributed
over
the
3
sampling
days
as
follows:
6
spoon/
hand
applications
on
day
1;
4
spoon/
hand
applications
on
day
2;
and
8
backpack
events
on
day
3.
Weather
was
typical
of
the
application
season
in
that
it
was
hot
and
humid.
Monitoring
was
completed
using
whole
body
dosimeters,
cotton
gloves,
cotton
caps,
and
personal
sampling
pumps
equipped
with
filters.
Regent
20GR
was
supplied
in
22
pound
boxes
which
was
loaded
directly
into
the
backpack
devices
or
buckets
for
the
spoon
applicators.
The
application
rate
for
fipronil
used
in
this
study
is
7.5
grams
of
Regent
20GR
(i.
e.,
0.15
grams
ai/
plant)
which
is
equivalent
to
about
0.26
lb
ai/
acre
(0.00033
lb
ai/
plant)
at
approximately
800
plants
per
acre.
The
numbers
of
acres
treated
ranged
from
approximately
0.75
to
1
acre.
The
pounds
of
active
ingredient
handled
ranged
from
about
a
quarter
to
half
a
pound
per
replicate.
Each
40
applicator
wore
whole
body
dosimeters
that
also
served
as
the
normal
work
clothing.
PVC
gloves
were
also
worn
over
cotton
gloves
which
served
as
the
dosimeters.
A
protection
factor
of
50
percent
was
used
by
the
Agency
to
calculate
exposure
levels
under
a
layer
of
normal
work
clothing.
Dosimeter
samples
were
segmented
into
arms,
legs,
and
torso
for
analysis.
Analysis
of
fipronil
residues
was
completed
with
gas
chromatography
and
electron
capture
detection.
The
limits
of
quantification
(LOQ)
were
9.7
µg
per
sample
for
all
media
used.
The
limit
of
detection
(LOD)
varied
for
each
media.
The
LOD
for
the
cotton
gloves
was
0.5
µg
per
sample,
0.10
µg
per
sample
for
the
air
filters,
and
2.0
to
4.0
µg
per
sample
for
the
whole
body
dosimeters
depending
upon
the
sample
analyzed.
Field
and
laboratory
recovery
data
were
generated
for
all
media.
Field
recovery
data
were
generated
in
a
manner
that
addressed
field
sampling,
field
storage,
transport,
laboratory
storage,
and
analysis.
However,
the
laboratory
recovery
data
were
indeterminate
because
the
sample
media
could
not
be
identified
for
each
reported
result.
The
overall
recovery
values
do
appear
to
be
quantitative.
Residues
were
corrected
for
the
overall
average
field
recovery
for
each
residue/
matrix
combination.
Generally,
recovery
was
adequate
for
all
media/
residue
combinations
(i.
e.,
all
correction
factors
were
greater
than
85
percent).
If
the
PHED
grading
criteria
are
applied
and
the
overall
laboratory
recovery
averages
are
used
all
residue/
matrix
combinations
are
considered
grade
"A"
data.
The
grade
"A"
criteria
require
laboratory
recovery
data
with
an
average
of
at
least
90
percent
and
a
coefficient
of
variation
of
15
or
less
accompanied
with
field
recoveries
that
are
at
least
70
percent
but
not
exceeding
120
percent.
Unit
exposure
values
were
calculated
using
the
data
from
the
study
and
a
commercial
spreadsheet
program.
The
exposures
that
were
calculated
were
normalized
by
the
amount
of
chemical
used,
the
duration
of
the
application
interval,
and
by
the
body
weight
of
the
individual
applicators
(see
table
below).
The
values
are
based
on
a
50
percent
clothing
penetration
factor
and
are
separated
for
each
equipment
type
monitored
in
this
study.
For
each
normalization
factor,
the
arithmetic
mean,
geometric
mean,
and
various
percentiles
were
calculated.
No
analyses
were
completed
with
these
data
to
ascertain
the
exact
type
of
distribution.
The
Agency
typically
uses
the
best
fit
values
from
the
Pesticide
Handlers
Exposure
Database
which
are
representations
of
the
central
tendency.
Considering
the
standard
practice,
the
Agency
will
use
the
geometric
mean
for
risk
assessment
purposes.
The
other
values
are
presented
for
comparative
purposes.
Table
7:
Unit
Exposure
Values
Obtained
From
Granular
Spoon
Application
Study
(MRID
452507
01)
Type
(mg
exp./
lb
ai
handled)
(mg
exp./
hour)
(mg
exp./
kg
body
weight/
day)
Dermal
Inhalation
Dermal
Inhalation
Dermal
Inhalation
Applications
with
a
Spoon
Arith.
Mean
2.875
0.106
0.433
0.016
0.025
0.001
Geo.
Mean
1.978
0.045
0.246
0.006
0.014
0.0003
Median
1.889
0.039
0.221
0.005
0.011
0.0003
25th
%tile
0.990
0.024
0.104
0.003
0.006
0.0001
75th
%tile
4.140
0.066
0.677
0.007
0.035
0.0004
90th
%tile
6.113
0.316
0.999
0.052
0.059
0.003
95th
%tile
7.276
0.402
1.190
0.066
0.072
0.004
99th
%tile
8.207
0.471
1.342
0.077
0.082
0.005
41
EPA
MRID
410547
01
(Propoxur
trigger
sprayer
study):
A
total
of
15
applicator
events
during
residential
applications
using
a
hand
operated
trigger
pump
sprayer,
attached
with
an
18
inch
hose
to
half
gallon
cans
containing
0.95
percent
propoxur,
were
completed
in
this
study.
The
study
was
completed
between
October
26
and
November
1,
1988
in
the
Kansas
City
Missouri
metro
area.
Each
person
monitored
in
the
study
was
a
Bayer
(the
sponsor
corporation)
employee.
Three
employees
were
used
to
complete
all
replicates.
In
each
replicate,
"each
applicator
used
a
separate
one
half
gallon
can
of
Raid
for
each
house.
The
cap
was
removed
from
the
top
of
the
can
and
the
hose
sprayer
was
attached
by
inserting
the
dip
tube
into
the
can
and
tightening
the
screw
cap.
The
sprayer
was
primed
by
pumping
the
trigger.
The
applicator
treated
the
outside
of
the
home
in
areas
where
pests
were
likely
to
be
found,
such
as
screens,
door
and
window
frames,
foundation
walls,
patios,
porches,
stoops,
and
decks.
When
the
application
was
completed,
the
hose
sprayer
was
secured
under
the
handle
of
the
can."
The
data
included
in
the
study
indicate
that
exposure
durations
ranged
from
9
to
21
minutes
per
replicate
and
the
amount
of
active
ingredient
handled
ranged
from
0.16
to
0.4
oz
(i.
e.,
0.01
to
0.025
lb
ai).
Dermal
(nonhand)
exposure
monitoring
during
each
replicate
was
completed
using
gauze
sponges
held
in
"aluminized
paper
holders"
with
an
open
sampling
surface
area
of
24.6
cm
2
while
hand
exposures
were
quantified
with
the
handwash
technique
(2
200
mL
aliquots
of
ethanol
per
hand
for
a
total
volume
of
800
mL
per
person).
Inhalation
exposures
were
monitored
using
standard
personal
sampling
pumps
operating
a
1
liter
per
minute
with
quartz
microfiber
filters.
Samples
were
collected
in
this
study
to
represent
exposures
when
a
person
was
wearing
normal
work
clothing
(i.
e.,
long
pants
and
long
sleeved
shirts)
and
chemical
resistant
gloves.
Analysis
of
propoxur
residues
was
completed
with
high
performance
liquid
chromatography,
post
column
derivatization,
and
fluorescence
detection.
The
limits
of
quantification
(LOQ)
were
10
µg
per
sample
for
the
handwash
solutions,
0.1
µg/
sample
for
the
inhalation
filters,
and
0.03
µg/
cm
2
for
the
dermal
patch
samples.
Field
and
laboratory
recovery
data
were
generated
for
all
media.
This
study
was
reviewed
in
September
1989
under
EPA
contract
68
02
4254
by
Versar.
The
values
used
for
regulatory
purposes
have
been
excerpted
from
that
review
(including
recovery
results).
Average
laboratory
recovery
for
all
media
ranged
from
99.2
to
109
percent
while
the
coefficients
of
variation
for
each
media
were
generally
less
than
5
(i.
e.,
for
the
patches,
the
CV
=
16.5).
Patches
and
filters
were
fortified
at
1
µg/
sample
while
hand
rinses
were
fortified
at
either
200
or
1000
µg/
sample.
Average
field
recovery
results
ranged
from
90.3
to
102.2
percent
while
coefficients
of
variation
also
were
generally
less
than
5
(i.
e.,
inside
patch
CV=
6.9).
Patches
were
fortified
at
levels
from
1
to
50
µg/
sample,
hand
rinses
were
fortified
at
200
µg/
sample,
and
filters
were
fortified
at
0.2
µg/
sample.
Unit
exposure
values
were
calculated
using
the
data
from
the
study
and
a
commercial
spreadsheet
program.
The
exposures
that
were
calculated
were
normalized
by
the
amount
of
chemical
used
by
individual
applicators
(Table
8).
42
Table
8:
Unit
Exposure
Values
Obtained
From
Propoxur
Trigger
Pump
Sprayer
Study
(MRID
410547
01)
Type
(mg
exp./
lb
ai
handled)
Dermal
Inhalation
Geometric
Mean
13.5
0.
123
Unit
exposure
values
excerpted
from
Versar
PHED
Data
review
under
Contract
68
02
4254
(9/
29/
89).
EPA
MRID
449722
01
(ORETF
Handler
Studies):
A
report
was
submitted
by
the
ORETF
(Outdoor
Residential
Exposure
Task
Force)
that
presented
data
in
which
the
application
of
various
products
used
on
turf
by
homeowners
and
lawncare
operators
(LCOs)
was
monitored.
All
of
the
data
submitted
in
this
report
were
completed
in
a
series
of
studies.
The
two
studies
that
monitored
LCO
exposure
scenarios
used
a
granular
spreader
(ORETF
Study
OMA001)
and
a
low
pressure,
high
volume
turf
handgun
(ORETF
Study
OMA002)
are
summarized
below.
OMA001:
A
loader/
applicator
study
was
performed
by
the
Outdoor
Residential
Exposure
Task
Force
(ORETF)
using
Dacthal
(active
ingredient
DCPA,
dimethyl
tetrachloroterephthalate)
as
a
surrogate
compound
to
determine
"generic"
exposures
of
lawn
care
operators
(LCOs)
applying
a
granular
pesticide
formulation
to
residential
lawns.
Surrogate
chemicals
were
chosen
by
the
Task
Force
for
their
representativeness
based
on
physical
chemical
properties
and
other
factors.
Dacthal,
which
was
the
surrogate
chemical
used
for
the
granular
spreader
and
low
pressure
hand
gun
sprayer
studies,
has
a
molecular
weight
of
331.97
and
a
vapor
pressure
of
1.6
x
10
6
,
and
is
believed
to
be
an
appropriate
surrogate
for
many
relatively
nonvolatile
pesticides.
The
study
was
designed
to
simulate
a
typical
work
day
for
a
LCO
applying
granular
pesticide
formulation
to
home
lawns.
Each
LCO
replicate
involved
loading
and
applying
approximately
3.3
lb
ai
(360
lb
formulated
product)
over
a
period
of
about
4
hours
to
15
simulated
residential
lawns
(6480
ft
2
each)
with
a
rotary
type
spreader.
The
average
industry
application
rate
of
2
lb
ai/
acre
was
simulated
(actual
rate
achieved
was
about
1.9
lb
ai/
acre).
The
monitoring
period
included
driving,
placing
the
spreader
onto
and
off
of
the
truck,
carrying
and
loading
the
formulation
in
the
spreader,
and
the
actual
application.
Incidental
activities
such
as
repairs,
cleaning
up
spills,
and
disposing
of
empty
bags
were
monitored.
A
total
of
40
replicates
(individual
application
events)
were
monitored
using
passive
dosimetry
(inner
and
outer
whole
body
dosimeters,
hand
washes,
face/
neck
wipes,
and
personal
inhalation
monitors
with
OVS
tubes).
The
inner
samples
represent
a
single
layer
of
clothing.
Inhalation
exposure
was
calculated
using
an
assumed
respiratory
rate
of
17
Lpm
for
light
work
(NAFTA,
1999),
the
actual
sampling
time
for
each
individual,
and
the
pump
flow
rate.
In
20
of
the
replicates,
the
subjects
wore
chemical
resistant
gloves
while
in
the
remaining
replicates,
no
gloves
were
worn.
No
gloves
were
worn
in
any
replicate
while
driving.
All
results
were
normalized
for
the
amount
of
active
ingredient
handled.
Nearly
all
samples
(for
every
body
part
and
for
inhalation)
were
above
the
level
of
quantitation
(LOQ)
for
dacthal.
Where
results
were
less
43
than
the
reported
LOQ,
½
LOQ
value
was
used
for
calculations,
and
no
recovery
corrections
were
applied.
The
overall
laboratory
recoveries
(83
101%)
and
field
recoveries
(73
98%).
The
unit
exposure
values
are
presented
in
Table
9
below.
[Note
the
inhalation
exposure
value
is
a
median
because
the
data
were
found
to
be
neither
normally
nor
lognormally
distributed.
All
dermal
values
are
geometric
means
as
the
data
were
lognormally
distributed.]
OMA002:
A
mixer/
loader/
applicator
study
was
performed
by
the
Outdoor
Residential
Exposure
Task
Force
(ORETF)
using
Dacthal
as
a
surrogate
compound
to
determine
"generic"
exposures
to
individuals
applying
a
pesticide
to
turf
with
a
low
pressure
"nozzle
gun"
or
"hand
gun"
sprayer.
Dermal
and
inhalation
exposures
were
estimated
using
wholebody
passive
dosimeters
and
breathing
zone
air
samples
on
OVS
tubes.
Inhalation
exposure
was
calculated
using
an
assumed
respiratory
rate
of
17
Lpm
for
light
work
(NAFTA,
1999),
the
actual
sampling
time
for
each
individual,
and
the
pump
flow
rate.
All
results
were
normalized
for
lb
ai
handled.
A
total
of
90
replicates
were
monitored
using
17
different
subjects.
Four
different
formulations
of
dacthal
[75%
wettable
powder
(packaged
in
4lb
and
24
lb
bags),
75%
wettable
powder
in
water
soluble
bags
(3
lb
bag),
75%
water
dispersible
granules
(
2
lb
bag)
and
55%
liquid
flowable
(2.5
Gal
container)]
were
applied
by
five
different
LCOs
to
actual
residential
lawns
at
each
site
in
three
different
locations
(Ohio,
Maryland,
and
Georgia)
for
a
total
of
fifteen
replicates
per
formulation.
An
additional
ten
replicates
at
each
site
were
monitored
while
they
performed
spray
application
only
using
the
75
percent
wettable
powder
formulation.
A
target
application
rate
of
2
lb
ai/
acre
was
used
for
all
replicates
(actual
rate
achieved
was
about
2.2
lb
ai/
acre).
Each
replicate
treated
a
varying
number
of
actual
client
lawns
to
attain
a
representative
target
of
2.5
acres
(1
hectare)
of
turf.
The
exposure
periods
averaged
five
hours
twenty
one
minutes,
five
hours
thirty
nine
minutes,
and
six
hours
twenty
four
minutes,
in
Ohio,
Maryland
and
Georgia,
respectively.
Average
time
spent
spraying
at
all
sites
was
about
two
hours.
All
mixing,
loading,
application,
adjusting,
calibrating,
and
spill
clean
up
procedures
were
monitored,
except
for
typical
end
of
day
clean
up
activities,
e.
g.
rinsing
of
spray
tank,
etc.
Dermal
exposure
was
measured
using
inner
and
outer
whole
body
dosimeters,
hand
washes,
face/
neck
washes,
and
personal
air
monitoring
devices.
All
test
subjects
wore
one
piece,
100
percent
cotton
inner
dosimeters
beneath
100
percent
cotton
long
sleeved
shirt
and
long
pants,
rubber
boots
and
nitrile
gloves.
Gloves
are
typically
worn
by
most
LCOs,
and
required
by
many
pesticide
labels
for
mixing
and
loading.
Overall,
residues
were
highest
on
the
upper
and
lower
leg
portions
of
the
dosimeters
In
general,
concurrent
lab
spikes
produced
mean
recoveries
in
the
range
of
78
120
percent,
with
the
exception
of
OVS
sorbent
tube
sections
which
produced
mean
recoveries
as
low
as
65.8
percent.
Adjustment
for
recoveries
from
field
fortifications
were
performed
on
each
dosimeter
section
or
sample
matrix
for
each
study
participant,
using
the
mean
recovery
for
the
closest
field
spike
level
for
each
matrix
and
correcting
the
value
to
100
percent.
The
unit
exposure
values
are
presented
in
Table
9
below.
[Note
the
data
were
found
to
be
lognormally
distributed.
As
a
result,
all
exposure
values
are
geometric
means.]
44
Table
9:
Unit
Exposure
Values
Obtained
From
ORETF
LCO
Studies
(MRID
449722
01)
Type
(mg
exp./
lb
ai
handled)
Dermal
Inhalation
Single
Layer,
No
Gloves
Single
Layer,
Gloves
Double
Layer,
Gloves
LCO
Push
Granular
Spreader
0.35
0.22
0.11
0.0071
LCO
Turfgun
(WP
Formulation)
No
Data
0.65
0.36
0.0066
All
unit
exposure
values
are
geometric
means
except
inhalation
value
for
granular
spreader.
Double
layer
value
calculated
using
a
50%
protection
factor.
Turfgun,
no
glove
data
were
not
back
calculated
using
a
90
percent
protection
factor
as
it
is
deemed
unreliable.
WP
formulation
in
WSP
packaging
used
for
turfgun
assessment
as
the
unit
exposures
for
this
scenario
were
slightly
higher
than
for
the
other
scenarios
and
deemed
representative
of
current
products/
packaging.
Pesticide
Handler
Exposure
Database
(PHED)
Version
1.1
(August
1998):
Chemical
specific
data
for
assessing
human
exposures
during
pesticide
handling
activities
were
submitted
to
the
Agency
in
support
of
one
occupational
exposure
scenario
for
the
reregistration
of
carbaryl.
It
is
the
policy
of
HED
to
combine
submitted
chemical
specific
data
with
that
from
the
Pesticide
Handlers
Exposure
Database
(PHED)
Version
1.1
when
appropriate
to
assess
handler
exposures
for
regulatory
actions
4
.
The
scenario/
chemical
specific
study
submitted
has
no
corresponding
scenario
in
PHED,
therefore,
unit
exposure
values
from
the
study
are
used
to
calculate
exposure
and
risk
for
the
use
pattern.
For
all
other
remaining
scenarios,
data
from
PHED
were
used
to
complete
the
assessment.
PHED
was
designed
by
a
task
force
of
representatives
from
the
U.
S.
EPA,
Health
Canada,
the
California
Department
of
Pesticide
regulation,
and
member
companies
of
the
American
Crop
Protection
Association.
PHED
is
a
software
system
consisting
of
two
parts
a
database
of
measured
exposure
values
for
workers
involved
in
the
handling
of
pesticides
under
actual
field
conditions
and
a
set
of
computer
algorithms
used
to
subset
and
statistically
summarize
the
selected
data.
Currently,
the
database
contains
values
for
over
1,700
monitored
individuals
(i.
e.,
replicates)
Users
select
criteria
to
subset
the
PHED
database
to
reflect
the
exposure
scenario
being
evaluated.
The
subsetting
algorithms
in
PHED
are
based
on
the
central
assumption
that
the
magnitude
of
handler
exposures
to
pesticides
are
primarily
a
function
of
activity
(e.
g.,
mixing/
loading,
applying),
formulation
type
(e.
g.,
wettable
powders,
granulars),
application
method
(e.
g.,
aerial,
groundboom),
and
clothing
scenarios
(e.
g.,
gloves,
double
layer
clothing).
Once
the
data
for
a
given
exposure
scenario
have
been
selected,
the
data
are
normalized
(i.
e.,
divided
by)
by
the
amount
of
pesticide
handled
resulting
in
standard
unit
exposures
(milligrams
of
exposure
per
pound
of
active
ingredient
handled).
Following
normalization,
the
data
are
statistically
summarized.
The
distribution
of
exposure
values
for
each
body
part
(e.
g.,
chest
upper
arm)
is
categorized
as
normal,
lognormal,
or
"other"
(i.
e.,
neither
normal
nor
lognormal).
A
central
tendency
value
is
then
selected
from
the
distribution
of
the
exposure
values
for
each
body
part.
These
values
are
the
arithmetic
mean
for
normal
distributions,
the
geometric
mean
for
lognormal
distributions,
and
the
median
for
all
"other"
distributions.
Once
selected,
the
central
tendency
values
for
each
body
part
are
composited
into
a
"best
fit"
exposure
value
representing
the
entire
body.
45
The
unit
exposure
values
calculated
by
PHED
generally
range
from
the
geometric
mean
to
the
median
of
the
selected
data
set.
To
add
consistency
and
quality
control
to
the
values
produced
from
this
system,
the
PHED
Task
Force
has
evaluated
all
data
within
the
system
and
has
developed
a
set
of
grading
criteria
to
characterize
the
quality
of
the
original
study
data.
The
assessment
of
data
quality
is
based
on
the
number
of
observations
and
the
available
quality
control
data.
These
evaluation
criteria
and
the
caveats
specific
to
each
exposure
scenario
are
summarized
in
Appendix
C,
Table
C1.
While
data
from
PHED
provide
the
best
available
information
on
handler
exposures,
it
should
be
noted
that
some
aspects
of
the
included
studies
(e.
g.,
duration,
acres
treated,
pounds
of
active
ingredient
handled)
may
not
accurately
represent
labeled
uses
in
all
cases.
HED
has
developed
a
series
of
tables
of
standard
unit
exposure
values
for
many
occupational
scenarios
that
can
be
utilized
to
ensure
consistency
in
exposure
assessments.
Unit
exposures
are
used
which
represent
different
levels
of
personal
protection
as
described
above.
Protection
factors
were
used
to
calculate
unit
exposure
values
for
varying
levels
of
personal
protection
if
data
were
not
available.
2.1.3
Occupational
Handler
Exposure
and
Non
Cancer
Risk
Estimates
The
occupational
handler
exposure
and
non
cancer
risk
calculations
are
presented
in
this
section.
Noncancer
risks
were
calculated
using
the
Margin
of
Exposure
(MOE)
which
is
a
ratio
of
the
body
burden
to
the
toxicological
endpoint
of
concern.
Body
burden
values
are
calculated
by
first
calculating
exposures
by
considering
application
parameters
(i.
e.,
rate
and
area
treated)
along
with
unit
exposure
levels.
Exposures
were
then
normalized
by
body
weight
and
adjusted
for
absorption
factors
as
appropriate
to
calculate
dose
levels
(i.
e.,
body
burdens).
MOEs
were
then
calculated.
Daily
Exposure:
The
daily
exposure,
daily
dose
and
hence
the
risks,
to
handlers
were
calculated
as
described
below.
The
first
step
was
to
calculate
daily
exposure
(dermal
or
inhalation)
using
the
following
formula:
Daily
Exposure
(mg
ai/
day)
=
Unit
Exposure
(mg
ai/
lb
ai)
x
Application
Rate
(lb
ai/
A)
x
Daily
Acres
Treated
(A/
day)
Where:
Daily
Exposure
=
Amount
deposited
on
the
surface
of
the
skin
that
is
available
for
dermal
absorption
or
amount
that
is
inhaled,
also
referred
to
as
potential
dose
(mg
ai/
day);
Unit
Exposure
=
Normalized
exposure
value
derived
from
August
1998
PHED
Surrogate
Exposure
Table
and
various
referenced
exposure
studies
noted
above
(mg
ai/
lb
ai);
Application
Rate
=
Normalized
application
rate
based
on
a
logical
unit
treatment
such
as
acres
or
gallons,
maximum
and
typical
values
are
generally
used
(lb
ai/
A);
and
Daily
Acres
Treated
=
Normalized
application
area
based
on
a
logical
unit
treatment
such
as
acres
(A/
day)
or
gallons
per
day
can
be
substituted
(gal/
day).
46
Inhalation
exposure
values
were
calculated
in
a
similar
manner.
The
only
difference
is
that
unit
exposure
values
representing
the
inhalation
route
were
used
that
were
calculated
using
PHED
and
standard
human
breathing
rates
(29
liters/
minute
and
an
8
hour
exposure).
[Note:
In
some
cases,
the
above
equation
has
been
substituted
by
an
algorithm
excerpted
from
the
Agency's
SOPs
For
Residential
Exposure
Assessment
(chapter
9)
that
calculates
exposures
based
on
the
percent
of
active
ingredient
applied
(e.
g.,
pet
treatment
calculations).
It
should
also
be
noted
that
HED
has
agreed
to
use
the
NAFTA
recommended
values
for
breathing
rate
rather
than
the
existing
rate
in
Series
875
Group
A
(i.
e.,
previously
known
as
Subdivision
U).
Series
875
Group
A
recommends
an
inhalation
rate
of
29
L/
min.
The
new
NAFTA
recommended
inhalation
rates
are
8.3,
16.7,
and
26.7
L/
min
for
sedentary
activities
(e.
g.,
driving
a
tractor),
light
activities
(e.
g.,
flaggers
and
mixer/
loaders
<
50
lb
containers),
and
moderate
activities
(e.
g.,
loading
>
50
lb
containers,
handheld
equipment
in
hilly
conditions),
respectively.
These
inhalation
reduction
factors
are
3.5
for
tractor
drivers,
1.7
for
mixer/
loaders
and
flaggers,
and
1.1
for
handheld
equipment.
These
changes
in
exposure
factors
will
be
programmed
into
the
next
version
of
the
handler
exposure
data
base
and
are
characterized
in
this
document
for
regulatory
risk
management
decisions.]
Daily
Dose:
Daily
dose
(inhalation
or
dermal)
was
then
calculated
by
normalizing
the
daily
dermal
exposure
value
by
body
weight
and
accounting
for
dermal
absorption
(i.
e.,
a
biologically
available
dose
resulting
from
dermal
exposure
was
then
calculated).
For
adult
handlers
using
carbaryl,
an
average
adult
body
weight
of
70
kg
was
used
for
all
exposure
scenarios
because
all
scenarios
were
occupational
and
the
toxic
effect
was
seen
in
males
and
females.
Additionally,
a
dermal
absorption
factor
of
12.7
percent
was
used
for
all
chronic
duration
dermal
calculations
based
on
an
absorption
study
in
rats.
A
21
day
dermal
administration
toxicity
study
in
rats
was
used
to
calculate
risks
for
short
and
intermediate
term
dermal
exposure.
In
cases
such
as
this,
a
default
value
of
100
percent
is
used
in
the
calculation.
It
should
also
be
noted
that
there
is
no
specific
inhalation
absorption
factor
that
is
available
for
carbaryl.
Therefore,
a
factor
of
100
percent
has
been
used
for
all
calculations.
Daily
dose
was
calculated
using
the
following
formula:
Where:
Average
Daily
Dose
=
The
amount
as
absorbed
dose
received
from
exposure
to
a
pesticide
in
a
given
scenario
(mg
pesticide
active
ingredient/
kg
body
weight/
day,
also
referred
to
as
ADD);
Daily
Exposure
=
Amount
deposited
on
the
surface
of
the
skin
that
is
available
for
dermal
absorption
or
amount
that
is
inhaled,
also
referred
to
as
potential
dose
(mg
ai/
day);
Absorption
Factor
=
A
measure
of
the
flux
or
amount
of
chemical
that
crosses
a
biological
boundary
such
as
the
skin
(%
of
the
total
available
absorbed);
and
Body
Weight
=
Body
weight
determined
to
represent
the
population
of
interest
in
a
risk
assessment
(kg).
The
handler
exposure
assessment
does
not
include
any
dietary
or
drinking
water
inputs.
47
Margins
of
Exposure:
Finally,
the
calculations
of
daily
dermal
dose
and
daily
inhalation
dose
received
by
handlers
were
then
compared
to
the
appropriate
endpoint
(i.
e.,
NOAEL
or
LOAEL)
to
assess
the
total
risk
to
handlers
for
each
exposure
route
within
the
scenarios.
Short
and
intermediate
term
dermal
MOEs
were
calculated
using
a
NOAEL
of
20.0
mg/
kg/
day
defined
in
the
rat
21
day
dermal
toxicity
study
(Table
1).
Short
term
inhalation
MOEs
were
calculated
using
a
NOAEL
of
1.0
mg/
kg/
day
defined
in
the
rat
developmental
neurotoxicity
and
rat
acute
neurotoxicity
studies
(Table
1).
Intermediate
term
inhalation
MOEs
were
calculated
using
a
NOAEL
of
1.0
mg/
kg/
day
defined
in
a
subchronic
neurotoxicity
study
in
rats.
Additionally,
when
required
for
a
limited
number
of
scenarios,
chronic
dermal
and
inhalation
MOEs
were
calculated
using
a
LOAEL
of
3.1
mg/
kg/
day
that
was
defined
in
a
1
year
dog
feeding
study.
All
MOE
values
were
calculated
separately
for
dermal
and
inhalation
exposure
levels
using
the
formula
below:
Where:
MOE
=
Margin
of
exposure,
value
used
by
the
Agency
to
represent
risk
or
how
close
a
chemical
exposure
is
to
being
a
concern
(unitless);
ADD
=
(Average
Daily
Dose)
or
the
amount
as
absorbed
dose
received
from
exposure
to
a
pesticide
in
a
given
scenario
(mg
pesticide
active
ingredient/
kg
body
weight/
day);
and
NOAEL
or
LOAEL
=
Dose
level
in
a
toxicity
study,
where
no
observed
adverse
effects
occurred
(NOAEL)
in
the
study
or
the
lowest
dose
level
where
an
adverse
effect
occurred
(LOAEL)
in
the
study
(mg
pesticide
active
ingredient/
kg
body
weight/
day).
It
is
important
to
present
risk
values
for
each
route
of
exposure
(i.
e.,
dermal
or
inhalation)
in
each
scenario
because
it
makes
determining
appropriate
risk
mitigation
measures
easier.
For
example,
if
overall
risks
are
driven
by
dermal
exposures
and
not
inhalation,
it
would
not
advisable
to
require
respirators
as
they
may
marginally
reduce
overall
risks.
It
is
also
important
to
present
overall
risk
estimates
for
each
scenario
considered
by
calculating
total
MOEs.
A
total
MOE
was
calculated
because
common
toxicity
endpoints
were
used
to
calculate
dermal
and
inhalation
risks
for
each
exposure
duration.
The
following
formula
is
used
to
calculate
total
MOE
values
by
combining
the
route
specific
MOEs:
MOE
total
=
1/((
1/
MOE
a)
+
(1/
MOE
b)
+....
(1/
MOE
n))
Where:
MOE
a,
MOE
b,
and
MOE
n
represent
MOEs
for
each
exposure
route
of
concern
A
margin
of
exposure
(MOE)
uncertainty
factor
of
100
is
considered
an
appropriate
risk
level
for
the
short
and
intermediate
term
risk
assessments
because
a
NOAEL
was
used
as
the
basis
for
the
48
assessment.
A
margin
of
exposure
(MOE)
uncertainty
factor
of
300
is
considered
an
appropriate
risk
level
for
the
chronic
risk
assessment
because
a
LOAEL
was
selected
from
the1
year
dog
feeding
study
as
the
basis
for
the
assessment.
Noncancer
Risk
Summary:
All
of
the
noncancer
risk
calculations
for
occupational
carbaryl
handlers
completed
in
this
assessment
are
included
in
Appendix
C
(Tables
1
9).
The
specifics
of
each
of
table
included
in
Appendix
C
are
described
below.
A
summary
of
the
results
for
each
exposure
scenario
is
also
provided
below
(please
refer
to
Appendix
C
for
more
details).
C
Appendix
C/
Table
1:
Sources
of
Exposure
Data
Used
in
the
Occupational
Carbaryl
Handler
Exposure
and
Risk
Calculations
Describes
the
sources
and
quality
of
the
exposure
data
used
in
all
of
the
occupational
handler
calculations.
C
Appendix
C/
Table
2:
Input
Parameters
For
Carbaryl
Occupational
Handler
Exposure
and
Risk
Calculations
Presents
the
numerical
unit
exposure
values
and
other
factors
used
in
the
occupational
handler
risk
assessments.
C
Appendix
C/
Table
3:
Margins
of
Exposure
For
Carbaryl
Occupational
Handler
Risk
Assessment
At
The
Baseline
Level
of
Personal
Protection
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short,
intermediate,
and
chronic
duration
exposures).
Represents
typical
work
clothing
or
a
long
sleeved
shirt
and
long
pants
with
no
respiratory
protection.
No
chemical
resistant
gloves
are
included
in
this
scenario.
Note
that
some
scenarios
have
no
baseline
dermal
exposure
values
(see
notes
on
Tables
1
and
2).
[Note:
The
calculations
from
this
table
have
been
used
to
develop
the
summary
in
Tables
7,
8,
and
9.]
C
AppendixC/
Table
4:
Margins
of
Exposure
For
Carbaryl
Occupational
Handler
Risk
Assessment
At
The
Minimum
Level
of
Personal
Protection
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short,
intermediate,
and
chronic
duration
exposures).
Represents
the
baseline
scenario
with
the
use
of
chemical
resistant
gloves
and
PF
5
respirators.
[Note:
The
calculations
from
this
table
have
been
used
to
develop
the
summary
in
Tables
7,
8,
and
9.]
C
Appendix
C/
Table
5:
Margins
of
Exposure
For
Carbaryl
Occupational
Handler
Risk
Assessment
At
The
Maximum
Level
of
Personal
Protection
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short,
intermediate,
and
chronic
duration
exposures).
Represents
the
baseline
scenario
with
the
use
of
an
additional
layer
of
clothing
(e.
g.,
a
pair
of
coveralls),
chemical
resistant
gloves,
and
a
PF
10
respirator.
[Note:
The
calculations
from
this
table
have
been
used
to
develop
the
summary
in
Tables
7,
8,
and
9.]
C
Appendix
C/
Table
6:
Margins
of
Exposure
For
Carbaryl
Occupational
Handler
Risk
Assessment
Using
Engineering
Controls
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short,
intermediate,
and
chronic
duration
49
exposures).
Represents
the
use
of
an
appropriate
engineering
control
such
as
a
closed
tractor
cab
or
closed
loading
system
for
granulars
or
liquids.
Engineering
controls
are
not
applicable
to
handheld
application
methods
there
are
no
known
devices
that
can
be
used
to
routinely
lower
the
exposures
for
these
methods.
[Note:
The
calculations
from
this
table
have
been
used
to
develop
the
summary
in
Tables
7,
8,
and
9.]
C
Appendix
C/
Table
7:
Combined
Short
Term
Margins
Of
Exposure
For
Carbaryl
Occupational
Handler
Risk
Assessment
Presents
combined
dermal
and
inhalation
MOEs
with
each
possible
combination
of
dermal
and
respiratory
protection
considered
in
this
assessment.
Results
for
exposure
durations
#
30
days
are
only
included
in
this
table
based
on
the
use
of
the
developmental
neurotoxicity
and
acute
neurotoxicity
studies
in
rats
to
define
the
NOAEL
for
this
duration.
[Note:
See
tables
3
through
6
for
calculations
of
specific
MOE
values.]
C
Appendix
C/
Table
8:
Combined
Intermediate
Term
Margins
Of
Exposure
For
Carbaryl
Occupational
Handler
Risk
Assessment
Presents
combined
dermal
and
inhalation
MOEs
with
each
possible
combination
of
dermal
and
respiratory
protection
considered
in
this
assessment.
Results
for
exposure
durations
>30
days
up
to
several
months
are
only
included
in
this
table
based
on
the
use
of
a
subchronic
neurotoxicity
study
in
rats
to
define
the
NOAEL
for
this
duration.
[Note:
See
tables
3
through
6
for
calculations
of
specific
MOE
values.]
C
Appendix
C/
Table
9:
Combined
Chronic
Margins
Of
Exposure
For
Carbaryl
Occupational
Handler
Risk
Assessment
Presents
combined
dermal
and
inhalation
MOEs
with
each
possible
combination
of
dermal
and
respiratory
protection
considered
in
this
assessment.
Results
for
exposures
that
occur
essentially
each
working
are
only
included
in
this
table
based
on
the
use
of
a
chronic
dog
feeding
study
to
define
the
LOAEL
for
this
duration.
[Note:
See
tables
3
through
6
for
calculations
of
specific
MOE
values.]
Tables
1
through
6
of
Appendix
C
provide
the
inputs
and
illustrate
how
the
calculations
were
performed
to
define
the
noncancer
risks
(i.
e.,
Margins
of
Exposure
or
MOEs)
for
carbaryl
handlers.
The
exposure
data
and
other
factors
which
were
used
represent
the
best
sources
of
data
currently
available
to
the
Agency
for
completing
these
kinds
of
assessments.
For
example,
maximum
application
rates
were
derived
directly
from
carbaryl
labels.
The
recent
use
and
usage
report
was
also
reviewed
to
define
average
application
rates
for
each
crop
or
group
of
crops
considered.
Exposure
factors
(e.
g.,
body
weight,
amount
treated
per
day,
protection
factors,
etc.)
are
all
standard
values
that
have
been
used
by
the
Agency
over
several
years
and
are
derived
from
peer
reviewed
sources
whenever
possible
(e.
g.,
Exposure
Factors
Handbook).
The
unit
exposure
values
are
the
best
available
estimates
of
exposure.
Some
unit
exposure
values
are
high
quality
while
others
represent
low
quality,
but
the
best
available,
data.
Data
quality
should
be
considered
in
the
interpretation
of
the
uncertainties
associated
with
each
risk
value
presented.
Please
identify
these
scenarios
based
on
information
provided
in
Appendix
C/
Table
1.
Additionally,
it
should
be
noted
that
the
animal
grooming
scenario
with
dusts
calculations
were
based
on
the
SOPs
For
Residential
Exposure
Assessment
(i.
e.,
10%
of
applied
is
considered
equivalent
to
the
dermal
exposure).
This
50
calculation
should
be
considered
only
as
a
rangefinder.
Tables
7,
8,
and
9
in
Appendix
C
provide
the
overall
results
of
the
risk
assessment
for
each
distinct
exposure
duration
considered
because
they
contain
the
combined
risk
values
for
each
scenario
using
several
combinations
of
personal
protection
(e.
g.,
short
term
combined
MOEs
are
presented
in
Table
7).
When
protective
measures
are
used
to
reduce
risks
it
is
appropriate
to
consider
how
each
method
will
reduce
the
associated
risks
and
the
burden
associated
with
the
use
of
that
method
(e.
g.,
gloves
are
thought
to
routinely
reduce
risks
from
dermal
exposures
by
90
percent
based
on
the
Agency
protection
factor
for
gloves).
It
should
be
noted
that
there
were
several
scenarios
which
were
identified
for
which
no
appropriate
exposure
data
are
known
to
exist.
These
include:
C
Animal
Grooming
Dust
Application;
C
Dust
applications
in
agriculture
(not
included
on
handler
tables
in
Appendix
C
but
considered
a
major
data
gap);
C
Handheld
Fogging
For
Mosquito
and
Other
Pest
Treatments;
C
Power
Backpack
Application;
C
Tree
Injection;
and
C
Drenching/
dipping
seedlings
[Note:
The
mixing/
loading
component
only
of
this
scenario
has
been
addressed
quantitatively.]
Short
term
and
Intermediate
term
Risk
Summary:
Short
term
and
intermediate
term
risks
were
calculated
for
different
exposure
scenarios
at
different
levels
of
personal
protection
as
illustrated
in
Tables
7
and
8
of
Appendix
C,
respectively.
The
results
and
trends
for
both
the
short
term
and
intermediate
term
calculations
are
identical
because
all
exposure
inputs
were
similar
and
the
NOAEL
values
of
20
mg/
kg/
day
for
dermal
exposures
and
1
mg/
kg/
day
for
inhalation
exposures
are
the
same
for
both
durations.
The
only
difference
is
the
source
of
the
NOAELs
selected
for
the
inhalation
risk
assessment.
The
short
term
values
were
determined
based
on
rat
developmental
neurotoxicity
and
acute
neurotoxicity
studies
while
the
intermediate
term
NOAEL
was
defined
using
a
subchronic
neurotoxicity
study
in
rats.
Therefore,
for
economy,
the
results
for
both
shortand
intermediate
term
occupational
handlers
have
been
summarized
together
in
this
section.
[Note:
If
risk
estimates
were
altered
because
of
additional
data
or
other
reason,
then
separate
sections
would
be
presented
as
appropriate.]
In
most
scenarios,
MOEs
meet
or
exceed
the
required
uncertainty
factor
of
100
at
some
level
of
personal
protection.
For
the
most
part,
current
label
requirements
for
personal
protection
(single
layer
clothing,
gloves,
and
no
respirator)
appear
to
be
generally
inadequate
for
most
scenarios
except
51
for
operations
where
exposures
and/
or
the
amount
of
chemical
used
is
low.
Table
10
summarizes
the
results
for
short
term
and
intermediate
term
occupational
handlers.
[Note:
Scenarios
where
MOEs
are
still
of
concern
(i.
e.,
<100)
for
any
personal
protection
considered
are
highlighted
and
the
minimum
required
PPE
is
also
highlighted
if
it
exceeds
current
label
requirements.]
Table
10:
Summary
of
Short/
Intermediate
Term
Occupational
Handler
Noncancer
Risks
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
MOEs
Min.
Req.
PPE
Mixer/
Loaders
1a
Dry
Flowable:
Aerial/
Chemigation
1
2
(wheat/
corn)
2
5
(veg.,
stone
fruit,
24C
on
oysters)
1200
350
363
726
498
1244
EC
EC
1b
Dry
Flowable:
Airblast
7.5
16
(various
fruit
&
nut
trees)
5
(nuts)
1.1
3
(pome
&
stone
fruit,
grapes)
40
40
40
1360
2902
101
143
391
EC
SL/
GL/
PF5
Baseline
1c
Dry
Flowable:
Groundboom
1.5
2
(wheat/
corn)
2
(strawberry/
veg)
8
(turf/
golf
courses)
4
(turf/
golf
courses)
200
80
40
40
2177
2902
107
2721
108
EC
Baseline
EC
Baseline
1d
Dry
Flowable:
High
Press
HW/
ROW
Sprayer
4
lb
ai/
100
gal
(poultry)
1000
gal
430
Baseline
1e
Dry
Flowable:
Low
press./
High
Vol.
Turfgun
4
8
(LCO
on
turf)
5
430
860
Baseline
1f
Dry
Flowable:
Wide
area
aerial
2
(rangeland/
forestry)
7500
58
MOE
<
100
2a
Granular:
Aerial
Application
2
(corn)
2
(corn)
1200
350
688
146
EC
SL/
GL/
PF5
2b
Granular:
Solid
broadcast
spreader
1.5
(wheat/
corn)
2
(wheat/
corn)
2
(vegetables)
6
(turf/
golf
courses)
9
(turf/
golf
courses)
200
200
80
40
40
110
256
206
138
284
Baseline
SL/
GL/
PF5
Baseline
Baseline
SL/
GL/
PF5
3a
Liquid:
Aerial/
Chemigation
1.5
2
(wheat,
max
corn)
1
(avg.
corn)
5
(stone
fruit)
2
(vegetables)
1200
1200
350
350
57
76
114
78
103
All
MOEs
<
100
EC
MOE<
100
DL/
GL/
PF10
3b
Liquid:
Airblast
Application
16
(Citrus
24C
in
California)
7.5
(Citrus)
5
(Nuts)
1.1
3
(Grapes,
pome
&
stone
fruit)
40
40
40
40
100
168
149
248
677
DL/
GL/
PF10
SL/
GL/
PF5
SL/
GL/
NR
SL/
GL/
NR
3c
Liquid:
Groundboom
1.5
(wheat)
2
(corn)
2
(strawberries)
8
(turf/
golf
courses)
4
(turf/
golf
courses)
200
200
80
40
40
168
126
186
157
186
SL/
GL/
PF5
SL/
GL/
PF5
SL/
GL/
NR
SL/
GL/
PF5
SL/
GL/
NR
3d
Liquid:
High
Press
HW/
ROW
Sprayer
4
lb
ai/
100
gal
(poultry)
1000
gal
745
SL/
GL/
NR
Table
10:
Summary
of
Short/
Intermediate
Term
Occupational
Handler
Noncancer
Risks
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
MOEs
Min.
Req.
PPE
52
3e
Liquid:
Low
press./
High
Vol.
Turfgun
4
8
(LCO
on
turf)
5
745
1489
SL/
GL/
NR
3f
Liquid:
Wide
area
aerial
2
(Range/
Forestry)
0.016
(Mosquito
adulticide)
0.15
(Mosquito
adulticide)
1
(Mosquito
adulticide)
7500
7500
7500
7500
9
248
121
18
MOE
<
100
SL/
GL/
NR
EC
MOE
<
100
3g
Liquid:
Wide
area
ground
0.016
(Mosquito
adulticide)
0.15
(Mosquito
adulticide)
1
(Mosquito
adulticide)
3000
3000
3000
621
112
45
SL/
GL/
NR
SL/
GL/
PF5
MOE
<
100
4a
Wettable
Powders:
Aerial
1
2
(Wheat/
corn)
5
(stone
fruit)
2
(vegetables)
1200
350
350
40
80
55
137
All
MOEs
<
100
MOE
<
100
EC
4b
Wettable
Powders:
Airblast
16
(Citrus
24C
in
California)
1.1
7.5
(Citrus,
nuts,
grapes,
pome
&
stone
fruit)
40
40
150
320
2180
EC
EC
4c
Wettable
Powders:
Groundboom
1.5
2
(wheat/
corn)
2
(strawberries)
4
8
(turf/
golf
courses)
200
80
40
240
320
599
299
599
EC
EC
EC
4d
Wettable
Powders:
High
Press
HW/
ROW
Sprayer
4
lb
ai/
100
gal
(poultry)
1000
gal
102
SL/
GL/
PF5
4e
Wettable
Powders:
Low
press./
High
Vol.
Turfgun
4
(LCO
on
turf)
8
(LCO
on
turf)
5
5
102
205
SL/
GL/
PF5
SL/
GL/
PF5
4f
Wettable
Powders:
Wide
area
aerial
2
(Range/
Forestry)
7500
6
MOE<
100
Applicators
5a
Aerial:
Agricultural
uses,
liquid
sprays
1
1.5
(wheat/
avg.
corn)
2
(max
corn)
5
(stone
fruit)
2
(vegetables,
24C
on
oysters)
1200
1200
350
350
113
170
85
116
292
EC
MOE<
100
EC
EC
5b
Aerial:
Wide
area
uses,
liquid
sprays
2
(Range/
Forestry)
0.016
0.15
(Mosquito
adulticide)
1
(Mosquito
adulticide)
7500
7500
7500
14
181
1700
27
MOE<
100
EC
MOE<
100
5c
Aerial:
Agricultural
uses,
granular
applications
2
(corn)
2
(corn)
1200
350
21
72
MOE<
100
MOE<
100
6a
Airblast:
Agricultural
uses
16
(Citrus
24C
in
California)
2
7.5
(Citrus,
nuts,
grapes,
pome
&
max.
stone
fruit)
1.1
(avg.
stone
fruit)
40
40
40
105
224
841
123
EC
EC
SL/
GL/
PF5
6b
Airblast:
Wide
area
uses,
liquid
sprays
0.016
(Mosquito
adulticide)
0.15
(Mosquito
adulticide)
1
(Mosquito
adulticide)
3000
3000
3000
113
150
22
SL/
GL/
PF5
EC
MOE<
100
Table
10:
Summary
of
Short/
Intermediate
Term
Occupational
Handler
Noncancer
Risks
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
MOEs
Min.
Req.
PPE
53
7
Groundboom
1.5
2
(Wheat,
corn)
2
(Strawberries)
4
8
(Turf/
golf
course)
200
80
40
122
162
304
152
304
Baseline
Baseline
Baseline
8
Solid
broadcast
spreader
(granular)
1.
5
2
(Wheat,
corn)
2
(Strawberries)
4
8
(Turf/
golf
course)
200
80
40
103
138
258
115
172
Baseline
Baseline
Baseline
9
Aerosol
Can
0.
01
lb
ai/
can
2
cans
324
Baseline
10
Trigger
pump
sprayer
0.
01
lb
ai/
can
1
can
8772
SL/
GL/
NR
11
Right
of
way
sprayer
1.
5
lb
ai/
100
gallons
1000
gallons
199
SL/
GL/
NR
12
High
pressure
handwand
4
lb
ai/
100
gallons
1000
gallons
66
MOE<
100
13
Animal
groomer,
liquid
application
0.01
lb
ai/
dog
8
dogs
9.7
MOE<
100
14
Animal
groomer,
dust
application
(see
App
C/
Table
3)
0.2
lb
ai/
dog
8
dogs
8750
Baseline
(dermal
exp
only)
15
Granulars
&
baits
applied
by
hand
9
(Ornamentals
&
gardens)
1
3.8
MOE<
100
16
Granulars
&
baits
applied
by
spoon
9
(Ornamentals
&
garderns)
1
75.1
MOE<
100
Mixerr/
Loader/
Applicators
17
Low
pressure,
high
volume
turfgun
(ORETF
Data)
8
(LCO
Use
on
turf)
4
(LCO
Use
on
turf)
5
5
94
104
MOE<
100
SL/
GL/
PF5
18a
Wettable
powder,
low
pressure
handwand
1
lb
ai/
1000
ft
2
(poultry
house)
2%
solution
(ornamentals)
20,000
ft
2
40
gallons
8.3
135
MOE<
100
SL/
GL/
PF5
18b
Liquids,
low
pressure
handwand
1
lb
ai/
1000
ft
2
(poultry
house)
2%
solution
(ornamentals)
20,000
ft
2
40
gallons
127
1699
SL/
GL/
PF5
SL/
GL/
NR
19
Backpack
sprayer
1
lb
ai/
1000
ft
2
(poultry
house)
2%
solution
(ornamentals)
20,000
ft
2
40
gallons
42
565
MOE<
100
Baseline
20
Granular,
bellygrinder
9
(Turf)
1
27
MOE<
100
21
Granular,
push
type
spreader
9
(Turf)
5
124
SL/
GL/
PF5
22
Handheld
fogger
No
data
No
data
No
data
No
data
23
Power
backpack
No
data
No
data
No
data
No
data
24
Granular,
backpack
9
(Ornamentals)
1
1562
DL/
GL/
NR
25
Tree
injection
No
data
No
data
No
data
No
data
26
Drench/
dipping
forestry/
ornamentals
1.5
lb
ai/
100
gallons
(Ornamental/
seedling
dip)
100
gallons
199
SL/
GL/
NR
27
Sprinkler
can
2%
solution
(Ornamentals)
10
gallons
226
Baseline
Table
10:
Summary
of
Short/
Intermediate
Term
Occupational
Handler
Noncancer
Risks
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
MOEs
Min.
Req.
PPE
54
Flaggers
28a
Flagger:
liquid
sprays
2
(Corn)
2
(Vegetables)
1200
350
249
111
EC
Baseline
28b
Flagger:
granular
applications
2
(Corn)
2
(Vegetables)
1200
350
101
345
Baseline
Baseline
Baseline
=
Long
pants,
long
sleeved
shirts,
no
gloves
SL
=
Single
layer
clothing
with
or
without
gloves
(GL
or
NG)
DL
=
Double
layer
clothing
(i.
e.,
coveralls
over
SL)
with
or
without
gloves
(GL
or
NG)
EC
=
Engineering
controls
NR
=
No
respirator
PF5
=
Protection
factor
5
respirator
PF10
=
Protection
factor
10
respirator
Current
label
=
SL/
GL/
NR
Min.
Req.
PPE
=
level
of
PPE
where
MOEs
>
100,
where
current
label
is
exceeded
or
no
adequate
PPE
is
found,
results
are
bold.
MOEs
which
never
exceed
100
are
for
highest
feasible
type
of
mitigation
(e.
g.,
engineering
control
in
most
cases).
Chronic
Risk
Summary:
MOEs
were
calculated
for
only
a
limited
number
of
exposure
ornamental
use
scenarios
where
the
Agency
believes
that
this
kind
of
exposure
pattern
may
exist.
These
calculations
were
also
completed
at
different
levels
of
personal
protection
as
illustrated
in
Table
11
(Table
9
of
Appendix
C
summarized
below).
For
most
scenarios
(3
of
5),
MOEs
meet
or
exceed
the
required
uncertainty
factor
of
300
at
some
level
of
personal
protection.
The
granular
hand
application
scenarios
are
problematic.
The
uncertainty
factor
of
300
is
required
for
the
chronic
exposure
scenarios
because
a
LOAEL
and
not
a
NOAEL
was
used
for
risk
assessment
purpose
as
defined
in
a
chronic
dog
feeding
study
using
carbaryl.
It
is
Agency
policy
to
apply
an
additional
factor
of
3
to
the
overall
uncertainty
factor
when
using
a
LOAEL
for
risk
assessment
purposes.
Table
11:
Summary
of
Chronic
Occupational
Handler
Noncancer
Risks
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
MOEs
Min.
Req.
PPE
Applicators
15
Granulars
&
baits
applied
by
hand
9
(Ornamentals
&
gardens)
1
4.7
MOE<
300
16
Granulars
&
baits
applied
by
spoon
9
(Ornamentals
&
garderns)
1
92.6
MOE<
300
Mixer/
Loader/
Applicators
18a
Wettable
powder,
low
pressure
handwand
2%
solution
(ornamentals)
40
gallons
302
DL/
GL/
PF10
18b
Liquids,
low
pressure
handwand
2%
solution
(ornamentals)
40
gallons
3206
SL/
GL/
NR
Table
11:
Summary
of
Chronic
Occupational
Handler
Noncancer
Risks
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
MOEs
Min.
Req.
PPE
55
19
Backpack
sprayer
2%
solution
(ornamentals)
40
gallons
781
Baseline
Baseline
=
Long
pants,
long
sleeved
shirts,
no
gloves
SL
=
Single
layer
clothing
with
or
without
gloves
(GL
or
NG)
DL
=
Double
layer
clothing
(i.
e.,
coveralls
over
SL)
with
or
without
gloves
(GL
or
NG)
EC
=
Engineering
controls
NR
=
No
respirator
PF5
=
Protection
factor
5
respirator
PF10
=
Protection
factor
10
respirator
Current
label
=
SL/
GL/
NR
Min.
Req.
PPE
=
level
of
PPE
where
MOEs
>
300,
where
current
label
is
exceeded
or
no
adequate
PPE
is
found,
results
are
bold.
MOEs
which
never
exceed
300
are
for
highest
feasible
type
of
mitigation
(e.
g.,
PPE
in
most
cases).
2.1.4
Occupational
Handler
Exposure
and
Risk
Estimates
for
Cancer.
The
occupational
handler
exposure
and
cancer
risk
calculations
are
presented
in
this
section.
Cancer
risks
were
calculated
using
a
linear
low
dose
extrapolation
approach
in
which
a
Lifetime
Average
Daily
Dose
(LADD)
is
first
calculated
and
then
compared
with
a
Q1*
that
has
been
calculated
for
carbaryl
based
on
dose
response
data
in
the
appropriate
toxicology
study
(Q1*
=
8.75
x
10
4
(mg/
kg/
day)
1
).
Absorbed
average
daily
dose
(ADD)
levels
were
used
as
the
basis
for
calculating
the
LADD
values.
Section
2.1.3
above
describes
how
the
ADD
values
were
first
calculated
for
the
noncancer
MOE
calculations.
These
values
also
serve
as
the
basis
for
the
cancer
risk
estimates.
Dermal
and
inhalation
ADD
values
were
first
added
together
to
obtain
combined
ADD
values.
LADD
values
were
then
calculated
and
compared
to
the
Q1*
to
obtain
cancer
risk
estimates.
Lifetime
Average
Daily
Dose:
After
the
development
of
the
ADD
values,
the
next
step
required
to
calculate
the
carcinogenic
risk
is
to
amortize
these
values
over
the
working
lifetime
of
occupational
handlers
based
on
use
patterns,
this
results
in
the
LADD
for
that
use.
Product
labels
limit
use
to
every
7
to
10
days
or
a
seasonal
"lb
ai
per
acre"
limit.
Also,
according
to
available
use/
usage
data,
on
average,
carbaryl
is
applied
more
than
once
per
year
for
most
crops.
Based
on
this
information
and
due
to
the
number
and
variety
of
target
insects
and
crops
registered
for
carbaryl
applications,
the
Agency
considered
two
distinct
populations
in
the
cancer
risk
assessment
including
private
growers
at
10
use
events
per
year
and
commercial
applicators
that
would
have
a
more
frequent
use
pattern
of
30
days
per
year.
Finally,
a
35
year
career
and
a
70
year
lifespan
was
used
to
complete
the
calculations.
LADD
values
were
calculated
using
the
following
equation:
LADD
ADD
TreatmentFrequency
Days
year
WorkingDuration
Lifetime
=
×
×
365
/
Where:
Lifetime
Average
Daily
Dose
=
The
amount
as
absorbed
dose
received
from
exposure
to
a
56
pesticide
in
a
given
scenario
over
a
lifetime
(mg
pesticide
active
ingredient/
kg
body
weight/
day,
also
referred
to
as
LADD);
Average
Daily
Dose
=
The
amount
as
absorbed
dose
received
from
exposure
to
a
pesticide
in
a
given
scenario
on
a
daily
basis
(mg
pesticide
active
ingredient/
kg
body
weight/
day,
also
referred
to
as
ADD);
Treatment
Frequency
=
The
annual
frequency
of
an
application
by
an
individual
(days/
year);
Working
Duration
=
The
amount
of
a
lifetime
that
an
individual
spends
engaged
in
a
career
involving
pesticide
exposure
(35
years);
Lifetime
=
The
average
life
expectancy
of
an
individual
(70
years).
Cancer
Risks
:
Finally,
cancer
risk
calculations
were
completed
by
comparing
the
LADD
values
calculated
above
to
the
Q1*
for
carbaryl
(Q1*
=
8.75
x
10
4
(mg/
kg/
day)
1
,
see
Table
1
for
further
information).
The
Agency
considered
more
typical
users
in
these
calculations
(i.
e.,
private
growers
at
10
events
per
year)
as
well
as
more
frequent
users
that
might
represent
commercial
applicators
(i.
e.,
30
events
per
year).
Cancer
risk
values
were
calculated
using
the
following
equation:
Risk
LADD
Q
=
×
1
*
Where:
Risk
=
Probability
of
excess
cancer
cases
over
a
lifetime
(unitless);
Lifetime
Average
Daily
Dose
=
The
amount
as
absorbed
dose
received
from
exposure
to
a
pesticide
in
a
given
scenario
over
a
lifetime
(mg
pesticide
active
ingredient/
kg
body
weight/
day,
also
referred
to
as
LADD);
and
Q1*
=
Quantitative
dose
response
factor
used
for
linear,
lowdose
response
cancer
risk
calculations
(mg/
kg/
day)
1
.
The
Agency
has
defined
a
range
of
acceptable
cancer
risks
based
on
a
policy
memorandum
issued
in
1996
by
then
office
director,
Mr.
Dan
Barolo.
This
memo
refers
to
a
predetermined
quantified
"level
of
concern"
for
occupational
carcinogenic
risk.
In
summary,
this
policy
memo
indicates
occupational
carcinogenic
risks
that
are
1
x
10
6
or
lower
require
no
risk
management
action.
For
those
chemicals
subject
to
reregistration,
the
Agency
is
to
carefully
examine
uses
with
estimated
risks
in
the
10
6
to
10
4
range
to
seek
ways
of
cost
effectively
reducing
risks.
If
57
carcinogenic
risks
are
in
this
range
for
occupational
handlers,
increased
levels
of
personal
protection
would
be
warranted
as
is
commonly
applied
with
noncancer
risk
estimates
(e.
g.,
additional
PPE
or
engineering
controls).
Carcinogenic
risks
that
remain
above
1.0
x
10
4
at
the
highest
level
of
mitigation
appropriate
for
that
scenario
remain
a
concern.
Cancer
Risk
Summary
All
of
the
cancer
risk
calculations
for
occupational
carbaryl
handlers
completed
in
this
assessment
are
included
in
Appendix
C
(Tables
10
and
11).
The
specifics
of
each
of
table
included
in
Appendix
C
are
described
below.
A
brief
summary
of
the
results
for
each
exposure
scenario
is
also
provided
below.
C
Appendix
C/
Table
10:
Carbaryl
Occupational
Handler
Risks
For
Private
Growers
Presents
cancer
risks
for
combined
dermal
and
inhalation
for
private
growers
(i.
e.,
10
applications
per
year)
with
each
possible
combination
of
dermal
and
respiratory
protection
considered
in
this
assessment.
C
Appendix
C/
Table
11:
Carbaryl
Occupational
Handler
Risks
For
Commercial
Applicators
Presents
cancer
risks
for
combined
dermal
and
inhalation
for
commercial
applicators
(i.
e.,
30
applications
per
year)
with
each
possible
combination
of
dermal
and
respiratory
protection
considered
in
this
assessment.
Tables
1
through
6
of
Appendix
C
should
also
be
considered
as
they
illustrate
how
the
route
specific
ADD
values
were
calculated
which
are
the
basis
for
the
cancer
risk
values.
These
route
specific
ADD
values
were
added
and
applied
to
the
Q1*
value
to
calculate
the
cancer
risks
as
described
above.
Cancer
risks
for
private
growers
(i.
e.,
10
applications
per
year)
were
calculated
for
different
exposure
scenarios
at
different
levels
of
personal
protection
(Table10
of
Appendix
C).
All
scenarios
for
private
growers
have
risks
that
are
<1x10
4
at
some
level
of
personal
protection
specified
in
the
Barolo
memo.
In
fact,
for
all
but
one
scenario
(Scen
4f:
Mixing/
loading
Wettable
Powders
for
wide
area
aerial
applications)
cancer
risks
are
<1x10
4
at
current
label
requirements
for
personal
protection.
If
a
1x10
6
risk
level
is
specified
as
a
concern,
results
are
similar
in
that
risks
for
a
majority
of
scenarios
are
<1x10
6
at
current
label
requirements.
In
fact,
only
8
of
the
128
scenarios
considered
for
private
applicators
have
cancer
risks
>1x10
6
(and
less
than
1x10
4
)
even
when
the
most
protective
ensembles
of
either
protective
clothing
or
engineering
controls
are
considered.
As
with
the
risks
calculated
for
private
growers,
cancer
risks
for
commercial
applicators
(i.
e.,
30
applications
per
year)
were
calculated
for
different
exposure
scenarios
at
different
levels
of
personal
protection
(Table
11
of
Appendix
C).
Again,
risks
for
all
but
one
scenario
(Scen
4f:
Mixing/
loading
Wettable
Powders
for
wide
area
aerial
applications)
are
less
than
the
1x10
4
level
specified
in
the
Barolo
memo
at
current
label
requirements
for
personal
protection
(i.
e.,
risks
for
this
scenario
are
<
1x10
4
if
additional
protective
clothing
or
equipment
is
used).
If
a
1x10
6
risk
level
is
specified
as
a
concern
for
commercial
applicators,
results
indicate
that
risks
for
about
half
of
the
scenarios
considered
are
<1x10
6
at
current
label
requirements
and
that
only
21
of
the
128
scenarios
considered
have
cancer
risks
>1x10
6
(and
less
than
1x10
4
)
even
when
the
most
protective
ensembles
of
either
protective
clothing
or
engineering
controls
are
considered.
In
58
general,
the
cancer
risk
estimates
would
lead
to
less
restrictive
measures
when
compared
to
the
noncancer
results.
Table
12
below
provides
a
summary
of
the
cancer
risks
that
have
been
calculated
for
private
growers
and
commercial
applicators.
Table
12:
Summary
of
Occupational
Handler
Cancer
Risks
For
Private
Growers
and
Commercial
Applicators
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
Private
Growers
Commercial
Applicators
Risk
Min.
Req.
PPE
Risk
Min.
Req.
PPE
Mixer/
Loaders
1a
Dry
Flowable:
Aerial/
Chemigation
1
2
(wheat/
corn)
5
(stone
fruit)
2
(vegetables,
24C
on
oysters)
1200
350
350
3.7
to
7.4x10
8
5.4x10
8
1.0x10
6
EC
EC
SL/
GL/
PF10
1.1
to
2.2x10
7
1.6x10
7
6.5x10
8
EC
EC
EC
1b
Dry
Flowable:
Airblast
16
(Citrus,
24C
in
CA)
1.1
7.5
(grapes,
various
fruit
&
nut
trees)
40
40
1.0x10
6
6.9x10
8
to
4.7x10
7
Baseline
Baseline
5.9x10
8
1.4
to
9.3x10
7
EC
DL/
GL/
PF10
1c
Dry
Flowable:
Groundboom
2
(corn)
1.5
(wheat)
2
(strawberry/
veg)
8
(turf/
golf
courses)
4
(turf/
golf
courses)
200
200
80
40
40
4.7x10
7
6.3x10
7
2.5x10
7
5.0x10
7
2.5x10
7
Baseline
Baseline
Baseline
Baseline
Baseline
1.0x10
6
3.7x10
8
7.5x10
7
1.0x10
6
7.5x10
7
DL/
GL/
NR
EC
Baseline
DL/
GL/
PF5
Baseline
1d
Dry
Flowable:
High
Press
HW/
ROW
Sprayer
4
lb
ai/
100
gal
(poultry)
1000
gal
6.3x10
8
Baseline
1.9x10
7
Baseline
1e
Dry
Flowable:
Low
press./
High
Vol.
Turfgun
4
8
(LCO
on
turf)
5
3.1
to
6.3x10
8
Baseline
9.4x10
8
to
1.9x10
7
Baseline
1f
Dry
Flowable:
Wide
area
aerial
2
(rangeland/
forestry)
7500
4.6x10
7
EC
1.4x10
6
All
<
1x10
6
2a
Granular:
Aerial
Application
2
(corn)
2
(corn)
1200
350
5.0x10
7
3.3x10
7
SL/
GL/
PF5
Baseline
9.5x10
7
9.9x10
7
DL/
GL/
PF5
Baseline
2b
Granular:
Solid
broadcast
spreader
1.5
2
(wheat/
corn)
2
(vegetables)
6
9
(turf/
golf
courses)
200
80
40
1.4
to
1.9x10
7
7.6x10
8
1.1
to
1.7x10
7
Baseline
Baseline
Baseline
4.3
to
5.7x10
7
2.3x10
7
3.4
to
5.1x10
7
Baseline
Baseline
Baseline
3a
Liquid:
Aerial/
Chemigation
1
(avg.
corn)
1.5
(wheat)
2
(corn)
5
(stone
fruit)
2
(vegetables)
1200
1200
1200
350
350
9.7x10
7
9.9x10
7
8.5x10
7
9.5x10
7
4.9x10
7
SL/
GL/
PF5
DL/
GL/
PF5
SL/
GL/
NR
SL/
GL/
PF5
SL/
GL/
NR
1.1x10
6
1.4x10
6
7.2x10
7
1.1x10
6
8.6x10
7
All
<
1x10
6
All
<
1x10
6
EC
All
<
1x10
6
DL/
GL/
PF5
3b
Liquid:
Airblast
Application
16
(citrus,
24C
in
CA)
1.1
7.5
(grapes,
various
fruit
&
nut
trees)
40
40
4.5x10
7
3.1x10
8
to
2.1x10
7
SL/
GL/
NR
SL/
GL/
NR
1.0x10
6
9.3x10
8
to
6.4x10
7
SL/
GL/
PF5
SL/
GL/
NR
3c
Liquid:
Groundboom
1.5
2
(wheat/
corn)
2
(strawberries)
4
8
(turf/
golf
courses)
200
80
40
2.1
to
2.8x10
7
1.1x10
7
1.1
to
2.3x10
7
SL/
GL/
NR
SL/
GL/
NR
SL/
GL/
NR
6.4
to
8.5x10
7
3.4x10
7
3.4
to
6.8x10
7
SL/
GL/
NR
SL/
GL/
NR
SL/
GL/
NR
3d
Liquid:
High
Press
HW/
ROW
Sprayer
4
lb
ai/
100
gal
(poultry)
1000
gal
2.8x10
8
SL/
GL/
NR
8.5x10
8
SL/
GL/
NR
3e
Liquid:
Low
press./
High
Vol.
Turfgun
4
8
(LCO
on
turf)
5
1.4
to
2.8x10
8
SL/
GL/
NR
4.2
to
8.5x10
8
SL/
GL/
NR
Table
12:
Summary
of
Occupational
Handler
Cancer
Risks
For
Private
Growers
and
Commercial
Applicators
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
Private
Growers
Commercial
Applicators
Risk
Min.
Req.
PPE
Risk
Min.
Req.
PPE
59
3f
Liquid:
Wide
area
aerial
2
(Range/
Forestry)
0.016
(Mosquito
adulticide)
0.15
(Mosquito
adulticide)
1
(Mosquito
adulticide)
7500
7500
7500
7500
3.0x10
6
8.5x10
8
7.9x10
7
1.5x10
6
All
<
1x10
6
SL/
GL/
NR
SL/
GL/
NR
All
<
1x10
6
9.1x10
6
2.5x10
7
6.8x10
7
4.5x10
6
All
<
1x10
6
SL/
GL/
NR
EC
All
<
1x10
6
3g
Liquid:
Wide
area
ground
0.016
(Mosquito
Adulticide)
0.15
(Mosquito
adulticide)
1
(Mosquito
adulticide)
3000
3000
3000
3.4x10
8
3.2x10
7
6.0x10
7
SL/
GL/
NR
SL/
GL/
NR
EC
1.0x10
7
9.5x10
7
1.8x10
6
SL/
GL/
NR
SL/
GL/
NR
All
<
1x10
6
4a
Wettable
Powders:
Aerial
1.5
(Wheat)
2
(Corn
max)
1
(Corn
typ)
5
(stone
fruit)
2
(vegetables)
1200
1200
1200
350
350
4.6x10
7
6.1x10
7
3.1x10
7
4.4x10
7
1.8x10
7
EC
EC
EC
EC
EC
1.4x10
6
1.8x10
6
9.2x10
7
1.3x10
6
5.3x10
7
All
<
1x10
6
All
<
1x10
6
EC
All
<
1x10
6
EC
4b
Wettable
Powders:
Airblast
16
(Citrus
24C
in
California)
7.5
(Citrus)
5
(Nuts)
3
(Pome
&
stone
fruit)
2
(Grapes)
1.1(
Avg.
stone
fruit)
40
40
40
40
40
40
1.6x10
7
7.6x10
8
1.0x10
6
6.2x10
7
8.8x10
7
4.9x10
7
EC
EC
SL/
GL/
PF5
SL/
GL/
PF5
SL/
GL/
NR
SL/
GL/
NR
4.9x10
7
2.3x10
7
1.5x10
7
9.2x10
8
1.0x10
6
5.7x10
7
EC
EC
EC
EC
DL/
GL/
PF5
DL/
GL/
PF5
4c
Wettable
Powders:
Groundboom
1.5
(wheat)
2
(corn)
2
(strawberries)
8
(turf/
golf
courses)
4
(turf/
golf
courses)
200
200
80
40
40
7.6x10
8
1.0x10
7
8.3x10
7
8.1x10
8
8.3x10
7
EC
EC
SL/
GL/
PF5
EC
SL/
GL/
PF5
2.3x10
7
3.1x10
7
1.2x10
7
2.4x10
7
1.2x10
7
EC
EC
EC
EC
EC
4d
Wettable
Powders:
High
Press
HW/
ROW
Sprayer
4
lb
ai/
100
gal
(poultry)
1000
gal
4.4x10
7
SL/
GL/
NR
5.2x10
7
DL/
GL/
PF5
4e
Wettable
Powders:
Low
press./
High
Vol.
Turfgun
4
(LCO
on
turf)
8
(LCO
on
turf)
5
5
2.2x10
7
4.4x10
7
SL/
GL/
NR
SL/
GL/
NR
6.6x10
7
6.2x10
7
SL/
GL/
NR
SL/
GL/
PF5
4f
Wettable
Powders:
Wide
area
aerial
2
(Range/
Forestry)
7500
3.8x10
6
All
<
1x10
6
1.1x10
5
All
<
1x10
6
Applicators
5a
Aerial:
Agricultural
uses,
liquid
sprays
1
2
(wheat/
corn)
5
(stone
fruit)
2
(vegetables,
24C
on
oysters)
1200
350
350
1.6
to
3.2x10
7
2.3x10
7
9.2x10
8
EC
EC
EC
4.7
to
9.5x10
7
6.9x10
7
2.8x10
7
EC
EC
EC
5b
Aerial:
Wide
area
uses,
liquid
sprays
2
(Range/
Forestry)
0.016
(Mosquito
adulticide)
0.15
(Mosquito
adulticide)
1
(Mosquito
adulticide)
7500
7500
7500
7500
2.0x10
6
1.6x10
8
1.5x10
7
9.8x10
7
All
<
1x10
6
EC
EC
EC
5.9x10
6
4.7x10
8
4.4x10
7
3.0x10
6
All
<
1x10
6
EC
EC
All
<
1x10
6
5c
Aerial:
Agricultural
uses,
granular
applications
2
(corn)
2
(corn)
1200
350
6.2x10
7
1.8x10
7
EC
EC
1.9x10
6
5.5x10
7
All
<
1x10
6
EC
6a
Airblast:
Agricultural
uses
16
(Citrus
24C
in
California)
7.5
(Citrus)
5
(Nuts)
3
(Pome
&
stone
fruit)
2
(Grapes)
1.1
(Avg
pome
&
stone
fruit)
40
40
40
40
40
40
2.7x10
7
1.3x10
7
9.9x10
7
1.0x10
6
6.9x10
7
3.8x10
7
EC
EC
DL/
GL/
PF5
Baseline
Baseline
Baseline
8.2x10
7
3.9x10
7
2.6x10
7
1.5x10
7
1.0x10
7
7.9x10
7
EC
EC
EC
EC
EC
SL/
GL/
NR
Table
12:
Summary
of
Occupational
Handler
Cancer
Risks
For
Private
Growers
and
Commercial
Applicators
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
Private
Growers
Commercial
Applicators
Risk
Min.
Req.
PPE
Risk
Min.
Req.
PPE
60
6b
Airblast:
Wide
area
fogger
0.016
(Mosquito
adulticide)
0.15
(Mosquito
adulticide)
1
(Mosquito
adulticide)
3000
3000
3000
4.1x10
7
1.9x10
7
1.3x10
6
Baseline
EC
All
<
1x10
6
8.6x10
7
5.8x10
7
3.9x10
6
SL/
GL/
NR
EC
All
<
1x10
6
7
Groundboom
1.5
2
(Wheat/
corn)
2
(Strawberries)
8
(Turf/
golf
course)
4
(Turf/
golf
course)
200
80
40
40
1.3
to
1.7x10
7
6.9x10
8
1.4x10
7
6.9x10
8
Baseline
Baseline
Baseline
Baseline
3.9
to
5.2x10
7
2.1x10
7
4.1x10
7
2.1x10
7
Baseline
Baseline
Baseline
Baseline
8
Solid
broadcast
spreader
(granular)
1.5
2
(Wheat/
corn)
2
(Strawberries)
4
8
(Turf/
golf
course)
200
80
40
1.3
to
1.7x10
7
6.7x10
8
1.0
to
1.5x10
7
Baseline
Baseline
Baseline
3.8
to
5.0x10
7
2.0x10
7
3.0
to
4.5x10
7
Baseline
Baseline
Baseline
9
Aerosol
Can
0.01
lb
ai/
can
2
cans
8.7x10
8
Baseline
2.6x10
7
Baseline
10
Trigger
pump
sprayer
0.01
lb
ai/
can
1
can
3.1x10
9
SL/
GL/
NR
9.4x10
9
SL/
GL/
NR
11
Right
of
way
sprayer
1.5
lb
ai/
100
gallons
1000
gallons
4.3x10
7
Baseline
4.1x10
7
SL/
GL/
NR
12
High
pressure
handwand
4
lb
ai/
100
gallons
1000
gallons
6.6x10
7
SL/
GL/
PF5
1.1x10
6
All
<
1x10
6
13
Animal
groomer,
liquid
application
0.01
lb
ai/
dog
8
dogs
3.1x10
6
All
<
1x10
6
9.4x10
6
All
<
1x10
6
14
Animal
groomer,
dust
application
0.2
lb
ai/
dog
8
dogs
3.5x10
9
Baseline
1.0x10
8
Baseline
15
Granulars
&
baits
applied
by
hand
9
(Ornamentals
&
gardens)
1
8.0x10
6
All
<
1x10
6
2.4x10
5
All
<
1x10
6
16
Granulars
&
baits
applied
by
spoon
9
(Ornamentals
&
garderns)
1
4.6x10
7
SL/
GL/
NR
1.2x10
6
All
<
1x10
6
Mixerr/
Loader/
Applicators
17
Low
pressure,
high
volume
turfgun
(ORETF
Data)
8
(LCO
Use
on
turf)
4
(LCO
Use
on
turf)
5
5
3.1x10
7
6.1x10
7
SL/
GL/
NR
SL/
GL/
NR
9.7x10
7
9.2x10
7
DL/
GL/
PF5
SL/
GL/
NR
18a
Wettable
powder,
low
pressure
handwand
1
lb
ai/
1000
ft
2
(poultry
house)
2%
solution
(ornamentals)
20,000
ft
2
40
gallons
3.1x10
6
3.0x10
7
All
<
1x10
6
SL/
GL/
NR
9.2x10
6
9.0x10
7
All
<
1x10
6
SL/
GL/
NR
18b
Liquids,
low
pressure
handwand
1
lb
ai/
1000
ft
2
(poultry
house)
2%
solution
(ornamentals)
20,000
ft
2
40
gallons
2.1x10
7
1.2x10
8
SL/
GL/
PF5
SL/
GL/
NR
6.2x10
7
3.5x10
8
SL/
GL/
PF5
SL/
GL/
NR
19
Backpack
sprayer
1
lb
ai/
1000
ft
2
(poultry
house)
2%
solution
(ornamentals)
20,000
ft
2
40
gallons
7.0x10
7
4.8x10
8
DL/
GL/
PF5
Baseline
2.2x10
6
1.4x10
7
All
<
1x10
6
Baseline
20
Granular,
bellygrinder
9
(Turf)
1
1.1x10
6
All
<
1x10
6
3.4x10
6
All
<
1x10
6
21
Granular,
push
type
spreader
9
(Turf)
5
4.0x10
7
Baseline
8.2x10
7
SL/
GL/
NR
22
Handheld
fogger
No
data
No
data
No
data
No
data
No
data
No
data
23
Power
backpack
No
data
No
data
No
data
No
data
No
data
No
data
24
Granular,
backpack
9
(Ornamentals)
1
1.9x10
8
DL/
GL/
NR
5.8x10
8
DL/
GL/
NR
25
Tree
injection
No
data
No
data
No
data
No
data
No
data
No
data
Table
12:
Summary
of
Occupational
Handler
Cancer
Risks
For
Private
Growers
and
Commercial
Applicators
Scenario
Rate
(lb
ai/
acre)
[unless
noted]
Area
Treated
(acres/
day)
[unless
noted]
Risk
Summary
Private
Growers
Commercial
Applicators
Risk
Min.
Req.
PPE
Risk
Min.
Req.
PPE
61
26
Drench/
dipping
forestry/
ornamentals
1.5
lb
ai/
100
gallons
(Ornamental/
seedling
dip)
100
gallons
1.1x10
7
SL/
GL/
NR
3.2x10
7
SL/
GL/
NR
27
Sprinkler
can
2%
solution
(Ornamentals)
10
gallons
1.3x10
7
Baseline
4.0x10
7
Baseline
Flaggers
28a
Flagger:
liquid
sprays
2
(Corn)
2
(Vegetables)
1200
350
7.2x10
7
2.1x10
7
Baseline
Baseline
3.5x10
7
6.3x10
7
EC
Baseline
28b
Flagger:
granular
applications
2
(Corn)
2
(Vegetables)
1200
350
2.1x10
7
6.1x10
8
Baseline
Baseline
6.2x10
7
1.8x10
7
Baseline
Baseline
Baseline
=
Long
pants,
long
sleeved
shirts,
no
gloves
SL
=
Single
layer
clothing
with
or
without
gloves
(GL
or
NG)
DL
=
Double
layer
clothing
(i.
e.,
coveralls
over
SL)
with
or
without
gloves
(GL
or
NG)
EC
=
Engineering
controls
NR
=
No
respirator
PF5
=
Protection
factor
5
respirator
PF10
=
Protection
factor
10
respirator
Current
label
=
SL/
GL/
NR
Min.
Req.
PPE
=
level
of
PPE
where
cancer
risks
>
1x10
6
,
where
current
label
is
exceeded
or
no
adequate
PPE
is
found,
results
are
bold.
Risks
which
never
exceed
1x10
6
are
for
highest
feasible
type
of
mitigation
(e.
g.,
engineering
control
in
most
cases).
2.1.5
Summary
of
Risk
Concerns
and
Data
Gaps
for
Handlers
Generally,
most
scenarios
have
risks
associated
with
them
that
meet
or
exceed
the
Agency's
uncertainty
factors
for
noncancer
risk
assessments
(i.
e.,
100
for
short
term
and
intermediate
term
and
300
for
chronic)
and
requirements
for
cancer
risk
results
(i.
e.,
range
of
1x10
6
to
1x10
4
as
defined
by
Office
Director
Barolo
in
1996)
at
some
level
of
personal
protection.
Current
carbaryl
labels
typically
require
that
handlers
wear
long
pants,
long
sleeved
shirts,
and
gloves.
Respirators
are
generally
not
required.
For
most
scenarios,
the
noncancer
risks
for
this
personal
protection
ensemble
do
not
meet
Agency
risk
requirements
and
additional
levels
of
personal
protection
are
required
to
achieve
Agency
risk
targets.
In
fact,
in
many
cases
engineering
controls
such
as
closed
loading
systems
or
closed
cab
tractors
are
needed.
The
Agency
does
have
risk
concerns
over
the
use
of
carbaryl
in
some
agricultural
and
other
occupational
settings
(i.
e.,
MOEs
at
any
level
of
personal
protection
are
<100
or
<300,
depending
on
the
duration).
As
would
be
expected,
these
scenarios
with
the
highest
associated
risk
also
have
high
daily
chemical
use
amounts
based
on
application
rates
or
high
acreages
treated
or
the
exposures
for
the
scenarios
in
question
are
relatively
high.
Generally,
the
areas
that
appear
to
be
problematic
include:
large
acreage
aerial
and
chemigation
applications
in
agriculture
or
for
wide
area
treatments
such
as
mosquito
control;
airblast
applications
at
higher
rates;
pet
grooming;
and
the
use
of
certain
handheld
equipment
for
applications
to
turf
or
gardens
(e.
g.,
bellygrinder).
This
general
trend
was
essentially
the
same
regardless
of
the
noncancer
toxicity
endpoints
which
were
considered
(e.
g.,
short
term,
intermediate
term).
Risks
for
corresponding
scenarios
based
on
cancer
concerns
were
generally
less
than
noncancer
results
across
all
scenarios.
In
fact,
in
all
but
one
scenario,
cancer
risks
were
<1x10
4
at
current
carbaryl
label
requirements
of
single
layer
clothing,
gloves,
and
no
respirator.
62
Several
data
gaps
were
also
identified
in
many
different
use
areas
that
include:
dust
use
for
animal
grooming
and
in
agriculture;
various
specialized
hand
equipment
application
methods
(e.
g.,
powered
backpack,
power
hand
fogger,
and
tree
injection);
and
nursery
operations
such
as
seedling
dips.
2.1.6
Recommendations
For
Refining
Occupational
Handler
Risk
Assessment
In
order
to
refine
this
occupational
risk
assessment,
data
on
actual
use
patterns
including
rates,
timing,
and
acreages
treated
would
better
characterize
carbaryl
risks.
Exposure
studies
for
many
equipment
types
that
lack
data
or
that
are
not
well
represented
in
PHED
(e.
g.,
because
of
low
replicate
numbers
or
data
quality)
should
also
be
considered
based
on
the
data
gaps
identified
above
and
based
on
a
review
of
the
quality
of
the
data
used
in
this
assessment.
Risk
managers
should
consider
that
the
risks
associated
with
current
label
requirements
for
personal
protection
generally
do
not
meet
Agency
risk
targets.
2.2
Occupational
Postapplication
Exposures
and
Risks
The
Agency
uses
the
term
"postapplication"
to
describe
exposures
to
individuals
that
occur
as
a
result
of
working
in
an
environment
that
has
been
previously
treated
with
a
pesticide
(also
referred
to
as
reentry
exposure).
The
agency
believes
that
there
are
distinct
job
functions
or
tasks
related
to
the
kinds
of
activities
that
occur
in
previously
treated
areas
such
as
harvesting
vegetables
in
a
treated
field.
Job
requirements
(e.
g.,
the
kinds
of
jobs
to
cultivate
a
crop),
the
nature
of
the
crop
or
target
that
was
treated,
and
the
how
chemical
residues
degrade
in
the
environment
can
cause
exposure
levels
to
differ
over
time.
Each
factor
has
been
considered
in
this
assessment.
The
scenarios
that
serve
as
the
basis
for
the
risk
assessment
are
presented
in
Section
2.2.1:
Occupational
Postapplication
Exposure
Scenarios.
The
exposure
data
and
assumptions
that
have
been
used
for
the
calculations
are
presented
in
Section
2.2.2:
Data
and
Assumptions
For
Occupational
Postapplication
Exposure
Scenarios.
The
calculations
and
the
algorithms
that
have
been
used
for
the
noncancer
elements
of
the
risk
assessment
as
well
as
the
calculated
risk
values
are
presented
in
Section
2.2.3:
Occupational
Postapplication
Exposure
and
Noncancer
Risk
Estimates
while
the
analogous
information
using
the
Q1*
for
cancer
estimates
are
presented
in
Section
2.2.4:
Occupational
Postapplication
Exposure
and
Risk
Estimates
For
Cancer.
Section
2.2.5:
Summary
of
Occupational
Postapplication
Risk
Concerns
and,
Data
Gaps
presents
the
overall
risk
picture
for
carbaryl.
Finally,
recommendations
are
presented
in
Section
2.2.6:
Recommendations
For
Refining
Occupational
Postapplication
Risk
Assessment.
2.2.1
Occupational
Postapplication
Exposure
Scenarios
Carbaryl
uses
are
extremely
varied
as
it
can
be
used
in
agriculture,
on
ornamentals,
on
turf
(golf
courses
and
lawns)
and
on
companion
animals
(e.
g.,
on
dogs
and
cats).
As
a
result,
a
wide
array
of
individuals
can
potentially
be
exposed
by
working
in
areas
that
have
been
previously
treated.
The
Agency
is
concerned
about
these
kinds
of
exposures
one
could
receive
in
the
workplace.
The
purpose
of
this
section
is
to
explain
how
postapplication
exposure
scenarios
were
developed
for
each
occupational
setting
where
carbaryl
can
be
used.
Exposure
scenarios
can
be
thought
of
as
ways
of
categorizing
the
kinds
of
exposures
that
occur
related
to
the
use
of
a
63
chemical.
The
use
of
scenarios
as
a
basis
for
exposure
assessment
is
very
common
as
described
in
the
U.
S.
EPA
Guidelines
For
Exposure
Assessment
(U.
S.
EPA;
Federal
Register
Volume
57,
Number
104;
May
29,
1992).
The
agency
uses
a
concept
known
as
the
transfer
coefficient
to
numerically
represent
the
post
application
exposures
one
would
receive
(i.
e.,
generally
presented
as
cm
2
/hour).
The
transfer
coefficient
concept
has
been
established
in
the
scientific
literature
and
through
various
exposure
monitoring
guidelines
published
by
the
U.
S.
EPA
and
international
organizations
such
as
Health
Canada
and
OECD
(Organization
For
Economic
Cooperation
and
Development).
The
establishment
of
transfer
coefficients
also
forms
the
basis
of
the
work
of
the
Agricultural
Reentry
Task
Force,
of
which,
Aventis
is
a
member.
The
transfer
coefficient
is
essentially
a
measure
of
the
contact
with
a
treated
surface
one
would
have
while
doing
a
task
or
activity.
These
values
are
defined
by
calculating
the
ratio
of
an
exposure
for
a
given
task
or
activity
to
the
amount
of
pesticide
on
leaves
(or
other
surfaces)
that
can
rub
off
on
the
skin
resulting
in
an
exposure.
For
postapplication
exposures,
the
amounts
that
can
rub
off
on
the
skin
are
measured
using
techniques
that
specifically
determine
the
amount
of
residues
on
treated
leaves
or
other
surfaces
(referred
to
as
transferable
residues)
rather
than
the
total
residues
contained
both
on
the
surface
and
absorbed
into
treated
leaves.
Transfer
coefficients
can
be
illustrated
by
the
following
example.
Consider
two
vegetable
fields
where
the
amount
of
chemical
on
treated
leaf
surfaces
that
can
rub
off
on
the
skin
is
the
same.
One
field
has
been
treated
with
chemical
A
while
the
other
field
has
been
treated
in
a
similar
manner
with
chemical
B.
If
an
individual
harvests
the
same
vegetables
for
a
day
in
each
field,
the
exposures
the
individual
would
receive
would
be
similar.
The
transfer
coefficient
would
also
be
similar
for
each
field
and
chemical
because
the
ratio
of
exposure
to
residue
would
be
the
same.
If
the
same
individual
would
do
another
activity
in
those
fields
such
as
scout
the
vegetables
for
pests
or
tie
the
vegetables,
the
exposures
would
be
different
as
would
the
resulting
transfer
coefficients
because
the
activity
that
resulted
in
the
exposures
is
different.
In
this
example,
three
distinct
transfer
coefficients
could
be
determined
for
vegetable
crops:
harvesting;
scouting;
and
tying.
The
Agency
has
developed
a
series
of
standard
transfer
coefficients
that
are
unique
for
variety
of
job
tasks
or
activities
that
are
used
in
lieu
of
chemical
and
scenario
specific
data.
As
with
the
handler
risk
assessment
process,
the
first
step
in
the
post
application
risk
assessment
process
is
to
identify
the
kinds
of
individuals
that
are
likely
to
be
exposed
to
carbaryl
after
application.
In
order
to
do
this
in
a
consistent
manner,
the
Agency
has
developed
a
series
of
general
descriptions
for
tasks
that
are
associated
with
post
application
exposures.
The
Agency
also
considers
whether
or
not
individuals
are
exposed
to
pesticides
as
part
of
their
employment
(referred
to
as
occupational
risk
assessments).
Common
examples
include:
agricultural
harvesters,
scouting
activities
in
agriculture,
crop
maintenance
tasks
(e.
g.,
irrigating,
hoeing
and
weeding),
and
turf
maintenance
(golf
course
mowing
and
sod
harvesting).
64
The
next
step
in
the
risk
assessment
process
is
to
define
how
and
when
chemicals
are
applied
in
order
to
determine
the
level
of
transferable
residues
to
which
individuals
could
be
exposed
over
time.
Wherever
available,
use
and
usage
data
are
included
in
this
process
to
define
values
such
as
application
rates
and
application
frequency.
The
Agency
always
completes
risk
assessments
using
maximum
application
rates
for
each
scenario
because
what
is
possible
under
the
label
(the
legal
means
of
controlling
pesticide
use)
must
be
evaluated,
for
complete
stewardship,
in
order
to
ensure
the
Agency
has
no
concern
for
the
specific
use.
Additionally,
whenever
the
Agency
has
additional
information,
such
as
typical
or
average
application
rates
or
frequency
data,
it
uses
the
information
to
further
evaluate
the
overall
risks
associated
with
the
use
of
the
chemical.
In
order
to
define
the
amount
of
transferable
residues
to
which
individuals
can
be
exposed,
the
Agency
relies
on
chemical
and
crop
specific
studies
as
described
in
the
Agency
guidelines
for
exposure
data
collection
(Series
875,
Occupational
and
Residential
Exposure
Test
Guidelines:
Group
B
Postapplication
Exposure
Monitoring
Test
Guidelines).
The
Agency
has
also
developed
a
standard
modeling
approach
that
can
also
be
used
to
predict
transferable
residues
over
time
in
lieu
of
chemical
and
scenario
specific
data
(best
described
in
the
Agency's
SOPs
For
Residential
Exposure
Assessment).
All
scenarios
were
evaluated
using
carbaryl
specific
DFR
dissipation
data.
Next,
assessors
must
understand
how
exposures
to
carbaryl
occur
(i.
e.,
frequency
and
duration)
and
how
the
patterns
of
these
occurrences
can
alter
the
effects
of
the
chemical
in
the
population
after
being
exposed
(referred
to
as
dose
response).
The
Agency
believes
that
carbaryl
exposures
can
occur
from
over
a
single
day
up
to
every
working
day
depending
on
the
crop
and
industry
being
considered.
This
is
supported
by
the
fact
that
several
areas
within
a
work
environment
may
be
treated
at
different
times.
For
example,
parts
of
agricultural
fields
in
a
localized
area
might
be
treated
over
several
weeks
because
of
an
infestation
with
a
concurrent
need
for
hand
labor
activities.
Therefore,
individuals
working
in
those
fields
might
be
exposed
from
contact
with
treated
foliage
over
an
extended
period
of
time
that
could
be
categorized
as
an
intermediate
term
exposure
as
they
work
on
different
sections
of
fields.
Three
different
types
of
noncancer
risk
calculations
were
required
for
each
exposure
duration
considered.
The
durations
of
exposure
that
were
considered
for
noncancer
toxicity
were
short
term
(
30
days),
intermediateterm
(30
days
up
to
several
months),
and
chronic
(every
working
day).
A
complete
array
of
calculations
was
completed
for
all
identified
exposure
scenarios
using
the
short
and
intermediateterm
endpoints
because
the
Agency
believes
that
carbaryl
uses
fit
the
criteria
for
both
of
these
durations.
The
only
calculations
that
were
completed
using
the
chronic
endpoint
were
limited
and
those
associated
with
the
greenhouse
and
floriculture
industries
where
these
kinds
of
exposures
may
occur.
Cancer
risks
were
also
calculated
using
a
linear,
low
dose
extrapolation
model
(i.
e.,
Q1*)
for
both
private
growers
(i.
e.,
10
days
per
year)
and
for
those
who
may
more
actively
use
carbaryl
such
as
a
professional
farmworker
(i.
e.,
30
days
per
year).
Inhalation
exposures
are
thought
to
be
negligible
in
outdoor
postapplication
scenarios
because
of
the
low
vapor
pressure
and
due
to
the
infinite
dilution
expected
outdoors.
As
such,
inhalation
postapplication
exposures
are
not
considered
in
this
assessment.
The
use
of
personal
protective
equipment
or
other
types
of
equipment
to
reduce
exposures
for
post
application
workers
is
not
considered
a
viable
alternative
for
the
regulatory
process
except
in
specialized
situations
(e.
g.,
a
rice
scout
will
wear
rubber
boots
in
flooded
paddies).
This
is
described
in
some
detail
in
the
Agency's
Worker
Protection
Standard
(40CFR170).
As
such,
an
65
administrative
approach
is
used
by
the
Agency
to
reduce
the
risks
and
is
referred
to
as
the
Restricted
Entry
Interval
or
REI.
The
REI
is
a
measure
of
the
amount
of
time
required
to
pass
after
application
of
a
pesticide
before
engaging
in
a
task
or
activity
in
a
treated
field.
Postapplication
risk
levels
are
generally
calculated
in
the
risk
assessment
process
on
a
chemical,
crop,
and
activityspecific
basis.
To
establish
REIs,
the
Agency
considers
postapplication
risks
on
varying
days
after
application.
[Note:
Current
labels
specify
REIs
of
12
hours
after
application
for
all
crop/
cultural
practice
combinations
while
Pre
Harvest
Intervals
(PHIs)
are
less
than
7
days
for
most
crops
with
some
as
long
as
28
days.]
The
Agency
has
used
the
basic
approach
described
above
since
the
mid
1980s
for
calculating
postapplication
risks
to
pesticides.
From
that
time
to
the
present,
several
revisions
and
modifications
were
made
to
Agency
policies
as
data
which
warranted
such
changes
became
available.
In
1995,
the
Agency
issued
a
Data
Call
In
for
postapplication
agricultural
data
that
prompted
the
formation
of
the
Agricultural
Reentry
Task
Force
(ARTF),
of
which
Aventis
is
a
member.
This
task
force
has
generated
a
number
of
exposure
studies
and
associated
documents
that
are
currently
under
review
by
the
Agency.
The
work
of
the
ARTF
is
not
yet
complete,
however,
sufficient
data
were
available
from
the
group
that
warranted
a
significant
interim
change
in
Agency
policy
related
to
the
data
which
were
already
available
as
the
efforts
of
the
ARTF
paralleled
the
Agency
push
for
tolerance
reassessment
stipulated
by
the
timelines
established
by
FQPA.
As
a
result
of
the
need
for
the
revision
and
using
the
latest
data,
the
Agency
developed
a
revised
policy
on
August
7,
2000
entitled
Policy
003.1
Science
Advisory
Council
For
Exposure
Policy
Regarding
Agricultural
Transfer
Coefficients.
The
revision
to
this
policy
entailed
linking
worker
activities
to
more
specific
crop/
agronomic
groupings
and
making
better
use
of
the
available
occupational
postapplication
exposure
data.
In
the
new
policy,
transfer
coefficients
were
selected
to
represent
the
activities
associated
with
18
distinct
crop/
agronomic
groupings
based
on
different
types
of
vegetables,
trees,
berries,
vine/
trellis
crops,
turf,
field
crops,
and
bunch/
bundle
crops
(e.
g.,
tobacco).
In
this
new
scheme
which
the
Agency
uses
to
develop
scenarios
for
occupational
postapplication
exposures,
carbaryl
uses
were
identified
in
all
of
the
crop
groupings
in
the
policy.
These
crop
groups
include:
C
Low
Berry
(e.
g.,
lowbush
blueberries,
cranberries,
strawberries);
C
Bunch/
bundle
(e.
g.,
bananas,
hops,
tobacco);
C
Field/
row
crops,
low/
medium
(e.
g.,
alfalfa,
barley,
beans,
cotton,
peanuts,
peas);
C
Field/
row
crops,
tall
(e.
g.,
corn,
sorghum,
sunflowers);
C
Cut
flowers
(e.
g.,
floriculture
crops);
C
Sugarcane;
C
Trees/
fruit,
deciduous
(e.
g.,
apples,
apricots,
cherry,
peaches,
pears);
C
Trees/
fruit,
evergreen
(e.
g.,
avocados,
Christmas
trees,
citrus);
C
Trees/
nut
(e.
g.,
almonds,
hazelnuts,
macadamia,
pecans,
walnuts);
C
Turf/
sod
(e.
g.,
golf
courses,
sod
farms);
C
Vegetable/
root
(e.
g.,
beets,
carrots,
onions,
potatoes,
turnips);
C
Vegetable/
cucurbit
(e.
g.,
cantelope,
cucumber,
squash,
watermelon);
C
Vegetable/
fruiting
(e.
g.,
eggplant,
pepper,
tomato,
okra);
C
Vegetable/
head
and
stem
brassica
(e.
g.,
brocolli,
cauliflower,
brussel
sprouts,
cauliflower);
C
Vegetables/
leafy
(e.
g.,
collards,
greens,
lettuce,
parsley,
spinach,
napa);
66
C
Vegetables/
stem
and
stalk
(e.
g.,
artichoke,
asparagus,
pineapple);
C
Vine/
trellis
(e.
g.,
blackberries,
blueberries,
grapes,
kiwi,
raspberries);
and
C
Nursery
crops
(e.
g.,
container
and
B&
B
ornamentals).
Within
each
agronomic
group,
a
variety
of
cultural
practices
are
required
to
maintain
the
included
crops.
These
practices
are
varied
and
typically
involve
light
to
heavy
contact
with
immature
plants
as
well
as
with
more
mature
plants.
The
Agency
selected
transfer
coefficient
values
in
its
revision
of
Policy
003
to
represent
this
range
of
exposures
within
each
agronomic
group.
In
the
policy,
transfer
coefficients
were
placed
in
1
of
5
generic
categories
based
on
the
exposures
relative
to
that
group.
These
5
categories
include:
very
low
exposure,
low
exposure,
medium
exposure,
high
exposure,
and
very
high
exposure.
Numerical
values
were
not
necessarily
assigned
to
each
category
for
each
crop
group.
Selections
depended
upon
the
actual
agronomic
practices
that
were
identified
by
the
Agency
for
each
group
(i.
e.,
some
groups
had
2
assigned
transfer
coefficients
while
others
had
5).
Carbaryl
can
be
used
in
each
of
the
agronomic
crop
groupings
described
above.
As
such,
all
agronomic
crop
group/
transfer
coefficients
were
used
to
calculate
postapplication
risks
for
carbaryl.
[Note:
Specific
transfer
coefficient
values
are
included
in
Appendix
E
of
this
document
which
contains
all
of
the
calculations.
The
transfer
coefficient
values
which
have
been
used
are
excerpted
directly
from
Agency
policy
003.
The
nursery
crop
group
data
have
not
yet
been
formally
included
in
EPA
Policy
3.
However,
the
studies
in
this
area
submitted
by
ARTF
have
been
reviewed
and
used
since
they
will
be
integrated
into
Policy
3
in
a
short
timeframe.]
The
revised
policy
on
transfer
coefficients
has
been
significantly
expanded
to
more
closely
link
job
practices
to
one
of
18
crop/
agronomic
groups
as
indicated
above.
It
has
also
more
clearly
defined
the
scope
of
the
policy
as
the
types
of
tasks/
job
functions
that
should
be
addressed
using
transfer
coefficients
are
more
clearly
defined
and
described.
The
policy
also
describes
which
kinds
of
jobs
result
in
exposures
that
cannot
be
addressed
with
transfer
coefficients
such
as
hand
harvesting
asparagus
(i.
e.,
because
there
is
no
foliar
contact)
or
those
that
are
of
special
concern
such
as
vacuuming
while
harvesting
tree
nuts.
The
revised
policy
also
describes
in
more
detail
those
exposures
that
are
considered
to
be
negligible
as
outlined
in
HED
Exposure
SAC
Policy
11:
Mechanized
Agricultural
Practices
and
Post
Application
Exposure
Assessments
(e.
g.,
mechanical
harvesting).
It
should
be
noted
that
mechanical
harvesting
and
other
similar
low/
no
exposure
activities
should
be
addressed
by
the
guidance
contained
in
Policy
11
which
is
based
on
the
Worker
Protection
Standard
guidance
for
such
activities
(40CFR
170).
If
there
are
exposures
that
are
of
special
concern,
then
additional
data
or
characterization
in
the
risk
mitigation
phase
of
the
reregistration
process
should
be
considered.
Exposures
that
are
thought
to
be
out
of
the
scope
of
Policy
003
for
carbaryl
are
presented
below.
A
discussion
of
associated
mechanized
practices
is
also
provided.
67
2.2.2
Data
and
Assumptions
for
Occupational
Postapplication
Exposure
Scenarios
A
series
of
assumptions
and
exposure
factors
served
as
the
basis
for
completing
the
occupational
postapplication
worker
risk
assessments.
Each
assumption
and
factor
is
detailed
below
on
an
individual
basis.
In
addition
to
these
values,
transfer
coefficient
values
were
used
to
calculate
risk
estimates.
Several
chemical
specific
residue
dissipation
studies
were
also
submitted
which
were
used
in
the
development
of
the
risk
values
.
The
transfer
coefficients
were
taken
from
the
Agency's
revised
policy
entitled
Policy
003.1
Science
Advisory
Council
For
Exposure
Policy
Regarding
Agricultural
Transfer
Coefficients
(August
7,
2000).
Each
of
these
factors
are
presented
below.
The
assumptions
and
factors
used
in
the
risk
calculations
include:
C
There
are
many
factors
that
are
common
to
handler
and
postapplication
risk
assessments
such
as
body
weights,
duration,
and
ranges
of
application
rates.
Please
refer
to
the
assumptions
and
factors
in
Section
2.1.2
for
further
information
concerning
these
values
which
are
common
to
both
handler
and
postapplication
risk
assessments.
In
the
postapplication
risk
assessment,
generally
only
maximum
application
rates
were
considered
because
of
the
complexity
of
the
calculations
(i.
e.,
short
term,
intermediate
term,
chronic,
and
cancer
endpoints
for
each
of
the
agronomic
groups
contained
in
Policy
003).
[Note:
The
transfer
coefficient
in
Policy
003
for
tree
fruit
thinning
has
been
reduced
since
the
issuance
of
the
policy
from
8000
cm2/
hour
to
3000
cm2/
hour
based
on
a
re
evaluation
of
the
data
from
the
cited
study.
This
modification
has
been
made
in
the
tree
fruit
group
and
any
other
scenarios
which
have
used
this
value.]
C
The
available
dislodgeable
foliar
residue
and
turf
transferable
residue
data
for
were
used
to
complete
all
postapplication
risk
assessments.
The
chemical
specific
residue
data
are
described
in
detail
below
and
summarized
in
Appendix
D.
These
data
indicate
that
the
percent
of
transferability
averages
approximately
16
percent
of
the
application
rate
for
the
agricultural
crops
using
the
Iwata
aqueous
solution/
leaf
punch
method
and
approximately
1.1
percent
for
the
turf
measurements
taken
using
the
new
ORETF
roller
method.
Given
these
values,
the
Agency
has
used
them
for
all
postapplication
crops
and
scenarios
as
the
transferability
is
in
the
appropriate
range
for
use
in
risk
assessments.
C
Aventis
Crop
Science
is
in
the
process
of
conducting
a
biomonitoring
study
for
carbaryl
during
apple
and
peach
thinning
and
harvesting
activities.
Based
on
discussions
with
Aventis
scientists,
it
appears
the
preliminary
results
of
this
study
essentially
confirm
the
dose
levels
calculated
in
the
Agency's
assessment
of
these
practices.
A
complete
review
of
these
data
will
be
completed
once
they
have
been
submitted
to
the
Agency.
68
C
The
use
of
common
engineering
controls
as
well
as
personal
protective
equipment
or
clothing
is
not
considered
a
practical
solution
for
mitigating
postapplication
worker
risks
as
described
in
the
Agency's
Worker
Protection
Standard
(40CFR170).
Of
course,
when
well
recognized
mechanized
options
are
available
such
as
for
harvesting
the
Agency
considers
them
in
the
overall
risk
picture
for
each
applicable
crop/
chemical/
cultural
practice
combination
(i.
e.,
mechanized
operations
are
also
discussed
in
40CFR170
and
in
the
Agency's
recently
revised
transfer
coefficient
policy
003).
In
lieu
of
PPE
or
engineering
controls
to
mitigate
risks,
the
Agency
uses
an
administrative
approach
by
establishing
Restricted
Entry
Intervals
which
are
essentially
the
time
it
takes
for
chemical
residues
to
dissipate
to
levels
where
jobs
can
be
done
at
exposure
levels
that
are
not
a
concern.
C
Exposures
were
calculated
to
reflect
chemical
specific
residue
dissipation
rates
over
time
coupled
with
surrogate
transfer
coefficients
as
outlined
in
the
Agency's
revised
policy.
Carbaryl
is
used
in
virtually
every
aspect
of
agriculture
but
only
4
dislodgeable
foliar
residue
studies
were
submitted
that
meet
current
Agency
guidelines
for
sampling
techniques
and
data
quality.
Studies
identified
in
the
literature
such
as
those
completed
by
Zweig
on
strawberries
in
1984
(t1/
2
=
4.1
days)
and
Iwata
in
1979
on
lemons
and
oranges
at
11.5
lb
ai/
acre
(t1/
2
=
14
days
and
t1/
2
=
22
days,
respectively)
were
considered
qualitatively
by
the
Agency
to
confirm
the
more
current
data.
[Note:
The
Iwata
data
indicate
a
longer
½
life
than
seen
in
the
current
data.
This
is
probably
due
to
the
high
application
rate
compared
to
the
current
carbaryl
labels.]
The
chemical
specific
dissipation
data
used
in
this
current
assessment
were
generated
in
studies
completed
by
the
ARTF
as
part
of
their
data
generation
effort.
These
studies
were
conducted
using
Iwata's
DFR
sampling
method
on
tobacco,
olives,
sunflowers,
and
cabbage.
A
turf
transferable
residue
(TTR)
study
was
also
completed
by
the
ORETF
using
the
new
roller
method.
The
Agency
uses
transfer
coefficients
in
different
agronomic
groups
as
described
above
to
complete
risk
assessments.
The
5
DFR
and
TTR
studies
were
used
as
the
transferable
residue
source
term
for
each
of
these
groups.
These
data
were
extrapolated
to
other
groups
based
on
the
nature
of
the
crop
and
application
method.
For
example,
the
olive
data
were
used
to
calculate
risks
for
all
tree
crops
because
airblast
(which
was
used
in
the
olive
study)
would
be
the
application
method
of
choice
for
tree
crops,
the
rates
are
similar,
and
the
plant
canopies
are
similar
(i.
e.,
can
impact
light
and
precipitation
levels
which
in
turn
impact
DFRs).
A
more
complete
description
of
how
the
data
have
been
used
is
provided
below.
C
As
described
in
the
handler
section
and
throughout
the
document,
short
term
noncancer
risks
were
calculated
by
comparing
single
day
exposures.
This
same
approach
was
used
in
the
postapplication
assessment
where
single
day
exposures
based
on
the
dissipation
of
carbaryl
residues
were
calculated
to
complete
the
short
term
risk
assessment
(i.
e.,
single
day
risks
were
calculated
based
on
daily
DFR
dissipation
values
over
time).
The
intermediate
and
chronic
postapplication
risk
calculations,
however,
differ
from
the
handler
calculations
for
these
extended
periods.
In
a
handler
assessment,
the
exposures
are
the
same
from
day
to
day
because
there
is
no
residue
dissipation
involved
(i.
e.,
if
one
sprays
whether
it
is
the
1
st
or
the
50
th
day
in
a
row
using
the
same
equipment,
the
exposures
would
be
similar
because
the
source
of
exposure
is
similar).
In
postapplication
assessments,
the
source
term
is
expected
to
diminish
because
of
residue
dissipation.
Hence,
for
the
intermediate
term
and
chronic
69
postapplication
risk
assessments,
averages
based
on
DFR
dissipation
and
an
appropriate
duration
for
the
endpoint
were
used
to
calculate
postapplication
risks.
In
the
intermediateterm
assessment,
a
30
day
average
was
used
to
calculate
risks
because
the
HIARC
identified
exposures
longer
than
30
days
as
intermediate
term
in
nature.
In
the
chronic
assessment,
a
30
day
average
was
used
based
on
the
likelihood
that
carbaryl
could
be
sprayed
at
least
once
a
month
in
the
ornamental
industry
(which
are
the
only
scenarios
identified
as
chronic
by
the
Agency).
There
are
many
approaches
that
can
be
used
in
the
calculation
of
intermediateterm
postapplication
risks
including
using
single
day
dose
levels
like
in
the
short
term
assessment
and
just
comparing
them
to
the
intermediate
term
endpoint.
This
is
effective
as
a
screening
approach
but
is
unlikely
to
actually
occur
based
on
simple
probability
(e.
g.,
finding
a
freshly
treated
field
30
days
in
a
row
would
be
less
likely
than
working
in
a
field
where
residues
are
dissipating
over
time).
C
Risks
were
calculated
using
the
generic
transfer
coefficients
that
represent
many
different
types
of
cultural
practices.
Transfer
coefficients
are
thought
to
be
generic
(i.
e.,
specific
to
a
crop/
activity
combination
but
independent
of
the
chemical
used
to
generate
them).
Several
values,
however,
included
in
the
Agency's
revised
policy
were
developed
using
carbaryl
data.
Because
carbaryl
can
be
used
so
widely,
every
crop/
cultural
practice
combination
represented
by
different
transfer
coefficients
included
in
the
Agency
policy
was
completed.
C
A
pseudo
first
order
kinetics
analysis
was
used
to
analyze
carbaryl
residue
dissipation
over
time
as
outlined
in
the
Agency's
draft
Series
875
Postapplication
Exposure
Monitoring
Guidelines.
A
more
sophisticated
curve
fitting
approach
was
not
warranted
because
the
correlation
coefficients
in
the
analysis
were
appropriate
and
the
data
have
been
used
generically
to
extrapolate
to
a
variety
of
other
crops
where
decay
rates
and
mechanisms
may
differ
(i.
e.,
any
sophistication
gained
with
a
curve
fitting
technique
would
be
lost
in
an
extrapolation
to
another
crop).
C
When
the
Agency
extrapolated
the
available
DFR
data
to
other
crops,
it
adjusted
the
data
for
differences
in
application
rate
using
a
simple
proportional
approach.
This
approach
seems
to
be
the
most
appropriate
given
the
data
which
are
available.
This
approach
is
commonly
used
in
Agency
postapplication
risk
assessments.
C
The
exposure
frequency
values
for
the
postapplication
cancer
risk
assessment
are
intended
to
consider
the
exposures
of
professional
farmworkers
and
those
growers/
users
who
do
their
own
hand
labor
(e.
g.,
harvesting
as
well
as
other
cultural
activities)
concurrently
with
carbaryl
applications.
As
a
result,
cancer
risks
for
all
postapplication
scenarios
have
been
assessed
using
30
days
per
year
for
professional
farmworkers
and
1/
3rd
of
that
for
private
growers
analogous
to
the
handler
assessment
completed
above.
C
In
postapplication
cancer
risk
assessments,
the
Agency
uses
a
tiered
approach.
In
this
case
LADD
(Lifetime
Average
Daily
Dose)
levels
were
calculated
by
amortizing
single
day
exposures
which
are
the
same
values
used
in
the
short
term
assessment
over
a
lifetime
using
the
10
and
30
days
per
year
frequency
values.
This
may
introduce
a
level
of
conservatism
into
the
assessment.
However,
it
does
not
appear
that
cancer
risks
would
drive
decisions
for
70
postapplication
exposure
scenarios
because
of
the
concerns
for
reentry
workers
from
noncancer
risks.
Therefore,
the
analysis
was
not
refined
further.
Potential
refinements
may
have
included
the
use
of
an
average
exposure
to
amortize
over
a
lifetime
or
the
area
under
the
appropriate
DFR
curve
could
be
integrated
and
amortized.
Postapplication
Studies:
A
total
of
five
studies
are
described
in
this
section..
One
study,
conducted
by
the
Aventis
Corporation,
quantifies
carbaryl
specific
turf
transferable
residues
in
3
different
states.
The
other
studies
were
all
conducted
by
the
ARTF
for
use
in
defining
generic
transfer
coefficients.
Carbaryl
is
one
of
the
compounds
that
was
selected
by
the
ARTF
as
a
surrogate
chemical
for
their
efforts.
These
studies
quantified
residue
dissipation
and
exposure
during
tobacco
harvesting,
during
scouting
in
sunflowers,
while
weeding
cabbage,
and
while
pruning
olive
trees.
The
DFR
component
of
those
studies
has
been
extracted
for
chemical
specific
use
in
this
risk
assessment.
The
transfer
coefficients
used
in
this
assessment
are
from
Agency's
interim
transfer
coefficient
policy
developed
by
HED's
Science
Advisory
Council
for
Exposure
using
proprietary
data
from
the
Agricultural
Re
entry
Task
Force
(ARTF)
database
(policy
#
3.1).
Each
study
can
be
identified
with
the
following
information.
Detailed
information
is
provided
in
Tables
1
through
8
of
Appendix
D.
Tables
1
through
7
contain
results
from
individual
studies
while
Table
8
contains
a
summary
of
the
critical
data
and
statistical
results.
The
studies
which
have
been
used
in
this
assessment
are
identified
below
followed
by
a
brief
summary
of
each:
C
"Determination
of
Dermal
and
Inhalation
Exposure
To
Reentry
Workers
During
Harvesting
In
Tobacco,
Study
Number:
ARF024"
EPA
MRID
450059
11;
Report
dated
July
20,
1999;
Authors;
Dennis
R.
Klonne,
Susan
C.
Artz,
Cassie
Prochaska,
Aaron
Rotondaro;
Sponsor:
Agricultural
Reentry
Task
Force;
Performing
Laboratories:
Field
Grayson
Research
LLC
and
Analytical
Morse
Laboratories.
C
"Determination
of
Dermal
and
Inhalation
Exposure
To
Reentry
Workers
During
Pruning
of
Olive
Trees,
Study
Number:
ARF033"
EPA
MRID
451751
02;
Report
dated
February
8,
2000;
Authors;
Dennis
R.
Klonne,
Randy
Fuller,
Richard
Honeycutt;
Sponsor:
Agricultural
Reentry
Task
Force;
Performing
Laboratories:
Field
HERAC,
Inc.
and
Analytical
Morse
Laboratories.
C
"Determination
of
Dermal
and
Inhalation
Exposure
To
Reentry
Workers
During
Scouting
in
Sunflower,
Study
Number:
ARF022"
EPA
MRID
450059
09;
Report
dated
September
28,
1999;
Authors;
Dennis
R.
Klonne,
Eric
Bruce,
Susan
Artz,
Casey
Howell;
Sponsor:
Agricultural
Reentry
Task
Force;
Performing
Laboratories:
Field
ABC
Laboratories
and
Analytical
Maxim
Technologies.
71
C
"Determination
of
Dermal
and
Inhalation
Exposure
To
Reentry
Workers
During
Weeding
In
Cabbage,
Study
Number:
ARF037"
EPA
MRID
451917
01;
Report
dated
May
30,
2000;
Authors;
Dennis
R.
Klonne,
Randy
Fuller,
Tami
Belcher;
Sponsor:
Agricultural
Reentry
Task
Force;
Performing
Laboratories:
Field
Excel
Research
Services
and
Analytical
Maxim
Technologies.
C
"Carbaryl:
Determination
of
Transferable
Residues
From
Turf
Treated
With
Dragon®
Sevin®
Liquid"
EPA
MRID
451143
01;
Report
dated
November
4,
1999;
Author;
Thomas
C.
Mester;
Sponsor:
Aventis
Corporation;
Performing
Laboratory:
ABC
Laboratories.
[Note
to
Risk
Managers:
There
are
no
data
compensation
issue
associated
with
the
use
of
the
ARTF
data
in
the
carbaryl
risk
assessment
because
the
Aventis
Corporation,
the
registrant
for
carbaryl,
is
a
member
of
the
ARTF.
The
task
force
has
submitted
proprietary
data
that
were
generated
using
carbaryl.
It
is
the
intention
of
HED's
Science
Advisory
Council
for
Exposure
that
the
transfer
coefficient
policy
will
be
periodically
updated
to
incorporate
additional
information
about
agricultural
practices
in
crops
and
new
data
on
transfer
coefficients.
Much
of
this
information
will
originate
from
exposure
studies
currently
being
conducted
by
the
ARTF,
from
further
analysis
of
studies
already
submitted
to
the
Agency,
and
from
studies
in
the
published
scientific
literature.]
MRID
450059
11
(tobacco
DFR
data):
This
study
contained
a
human
exposure
element
which
was
reviewed
separately
by
the
Agency
during
the
development
of
the
revised
policy
003
on
transfer
coefficients.
The
DFR
component
of
the
data
only
has
been
summarized
below
for
use
in
the
carbaryl
risk
assessment.
The
field
phase
of
this
study
was
conducted
at
a
single
site
near
Zebulon,
North
Carolina
which
is
in
a
major
growing
region
for
flue
cured
tobacco.
The
field
phase
of
the
study
was
conducted
during
the
period
from
July
1
to
August
13,
1998.
Sample
analyses
were
completed
by
October,
1998.
A
tractor
mounted
groundboom
sprayer
was
used
to
make
2
applications
of
Sevin
XLR
Plus,
a
liquid
flowable
formulation,
8
days
apart
at
an
application
rate
of
2
lb
ai/
acre.
Spray
volume
was
20
gallons
of
water
per
acre.
The
tobacco
plants
were
approximately
4.5
feet
tall
and
were
spaced
approximately
2
feet
within
each
row
while
the
rows
were
spaced
4
feet
apart
(i.
e.,
~5400
plants/
acre).
No
significant
precipitation
was
observed
in
this
study
until
at
least
7
days
after
application.
Triplicate
DFR
samples
were
collected
out
to
35
days
after
the
last
application
using
the
Iwata
method
(i.
e.,
a
total
surface
area
sampled
of
400
cm2/
sample
collected
with
a
1
inch
diameter
Birkestrand
leaf
punch
and
dislodged
with
a
0.01
percent
Aerosol
solution).
The
Limit
of
Quantitation
(LOQ)
in
this
study
was
1
µg/
sample
or
0.0025
µg/
cm
2
.
There
were
still
measurable
residues
35
days
after
application.
The
percent
transferability
of
the
0
day
sample
was
19
percent
of
the
application
rate.
Average
field
recovery
over
all
fortification
levels
was
114
percent
with
a
coefficient
of
variation
of
6.1.
The
results
of
the
study
are
presented
in
detail
in
Table
1
of
Appendix
D.
The
results
of
the
pseudo
first
order
statistical
analysis
of
the
data
presented
in
Appendix
D
are
summarized
below
in
Table
13.
72
Table
13:
Tobacco
DFR
Dissipation
Data
(MRID
450059
11)
Location
App.
Rate
(lb
ai/
acre)
App.
Method
Corr.
Coeff.
Slope
(Ln
TTR
vs.
t)
[T0]
(µg/
cm
2
)
T1/
2
(days)
Day
0
(%
trans.)
NC
2
Groundboom
0.957
0.205
4.26
3.4
19.0
MRID
451751
02
(olive
DFR
data):
This
study
contained
a
human
exposure
element
which
was
reviewed
separately
by
the
Agency
during
the
development
of
the
revised
policy
003
on
transfer
coefficients.
The
DFR
component
of
the
data
only
has
been
summarized
below
for
use
in
the
carbaryl
risk
assessment.
The
field
phase
of
this
study
was
conducted
at
a
single
site
near
Terra
Bella,
California
which
is
in
a
major
growing
region
for
olives.
The
field
phase
of
the
study
was
conducted
during
the
period
from
November
2
to
November
17,
1998.
Sample
analyses
were
completed
by
January,
1999.
A
typical
airblast
sprayer
was
used
to
make
a
single
application
of
Sevin
XLR
Plus,
a
liquid
flowable
formulation,
at
an
application
rate
of
7.65
lb
ai/
acre.
Spray
volume
was
758
gallons
of
water
per
acre.
The
olive
trees
were
approximately
20
feet
tall
and
were
spaced
approximately
28
feet
within
each
row
while
the
rows
were
spaced
28
feet
apart
(i.
e.,
~56
trees/
acre).
No
significant
precipitation
was
observed
in
this
study
until
at
least
7
days
after
application.
Triplicate
DFR
samples
were
collected
out
to
14
days
after
application
using
the
Iwata
method
(i.
e.,
a
total
surface
area
sampled
of
400
cm2/
sample
collected
with
a
1
inch
diameter
Birkestrand
leaf
punch
and
dislodged
with
a
0.01
percent
Aerosol
solution).
The
Limit
of
Quantitation
(LOQ)
in
this
study
was
1
µg/
sample
or
0.0025
µg/
cm
2
.
There
were
still
measurable
residues
14
days
after
application.
The
percent
transferability
of
the
0
day
sample
was
3.6
percent
of
the
application
rate.
Average
field
recovery
over
all
fortification
levels
was
109.7
percent
with
a
coefficient
of
variation
of
4.8.
The
results
of
the
study
are
presented
in
detail
in
Table
2
of
Appendix
D.
The
results
of
the
pseudo
first
order
statistical
analysis
of
the
data
presented
in
Appendix
D
are
summarized
below
in
Table
14.
Table
14:
Olive
DFR
Dissipation
Data
(MRID
451751
02)
Location
App.
Rate
(lb
ai/
acre)
App.
Method
Corr.
Coeff.
Slope
(Ln
TTR
vs.
t)
[T0]
(µg/
cm
2
)
T1/
2
(days)
Day
0
(%
trans.)
CA
7.65
Airblast
0.913
0.0988
3.067
7
3.
6
MRID
450059
09
(sunflower
DFR
data):
This
study
contained
a
human
exposure
element
which
was
reviewed
separately
by
the
Agency
during
the
development
of
the
revised
policy
003
on
transfer
coefficients.
The
DFR
component
of
the
data
only
has
been
summarized
below
for
use
in
the
carbaryl
risk
assessment.
The
field
phase
of
this
study
was
conducted
at
a
single
site
near
Northwood,
North
Dakota
which
is
in
a
major
growing
region
for
sunflowers.
The
field
phase
of
the
study
was
conducted
during
the
period
from
July
20
to
August
25,
1998.
Sample
analyses
were
completed
by
December,
1998.
A
fixed
wing
aircraft
was
used
to
make
2
applications
of
Sevin
XLR
Plus,
a
liquid
flowable
formulation,
7
days
apart
at
an
application
rate
of
1.5
lb
ai/
acre.
Spray
volume
was
3
gallons
of
water
per
acre.
The
sunflower
plants
were
approximately
4
feet
tall
and
were
spaced
approximately
0.5
feet
within
each
row
while
the
rows
were
spaced
2.5
feet
apart
(i.
e.,
~35000
plants/
acre).
No
significant
precipitation
was
observed
in
this
study
until
at
least
14
days
after
application.
DFR
samples
were
collected
out
to
28
days
after
the
last
application
using
the
Iwata
method
(i.
e.,
a
73
total
surface
area
sampled
of
400
cm2/
sample
collected
with
a
1
inch
diameter
Birkestrand
leaf
punch
and
dislodged
with
a
0.01
percent
Aerosol
solution).
The
Limit
of
Quantitation
(LOQ)
in
this
study
was
1
µg/
sample
or
0.0025
µg/
cm
2
.
There
were
still
measurable
residues
28
days
after
application.
The
percent
transferability
of
the
0
day
sample
was
32
percent
of
the
application
rate.
Average
field
recovery
over
all
fortification
levels
was
93.1
percent
with
a
coefficient
of
variation
of
9.1.
The
results
of
the
study
for
each
site
are
presented
in
detail
in
Table
3
of
Appendix
D.
The
results
of
the
pseudo
first
order
statistical
analysis
of
the
data
presented
in
Appendix
D
are
summarized
below
in
Table
15.
Table
15:
Sunflower
DFR
Dissipation
Data
(MRID
450059
09)
Location
App.
Rate
(lb
ai/
acre)
App.
Method
Corr.
Coeff.
Slope
(Ln
TTR
vs.
t)
[T0]
(µg/
cm
2
)
T1/
2
(days)
Day
0
(%
trans.)
ND
1.5
FW
Aerial
0.986
0.134
5.35
5.2
31.8
MRID
451917
01
(cabbage
DFR
data):
This
study
contained
a
human
exposure
element
which
was
reviewed
separately
by
the
Agency
during
the
development
of
the
revised
policy
003
on
transfer
coefficients.
The
DFR
component
of
the
data
only
has
been
summarized
below
for
use
in
the
carbaryl
risk
assessment.
The
field
phase
of
this
study
was
conducted
at
a
single
site
near
Fresno,
California
which
is
in
a
major
growing
region
for
cabbage.
The
field
phase
of
the
study
was
conducted
during
the
period
from
September
29
to
November
10,
1999.
Sample
analyses
were
completed
by
May,
2000.
A
tractor
drawn
groundboom
sprayer
was
used
to
make
2
applications
of
Sevin
XLR
Plus,
a
liquid
flowable
formulation,
7
days
apart
at
an
application
rate
of
2.07
lb
ai/
acre.
Spray
volume
was
31.1
gallons
of
water
per
acre.
The
cabbage
plants
were
approximately
8
to
10
inches
tall
and
were
spaced
approximately
1
feet
within
each
row
while
the
rows
were
spaced
3
feet
apart
(i.
e.,
~15000
plants/
acre).
No
significant
precipitation
was
observed
in
this
study.
All
irrigation
was
in
furrow
which
is
not
believed
to
impact
DFR
levels.
Triplicate
DFR
samples
were
collected
out
to
35
days
after
the
last
application
using
the
Iwata
method
(i.
e.,
a
total
surface
area
sampled
of
400
cm2/
sample
collected
with
a
1
inch
diameter
Birkestrand
leaf
punch
and
dislodged
with
a
0.01
percent
Aerosol
solution).
The
Limit
of
Quantitation
(LOQ)
in
this
study
was
1
µg/
sample
or
0.0025
µg/
cm
2
.
There
were
still
measurable
residues
35
days
after
application
in
1
of
the
3
samples
collected
while
all
samples
on
day
28
contained
detectable
residues.
The
percent
transferability
of
the
0
day
sample
was
10.9
percent
of
the
application
rate.
Average
field
recovery
over
all
fortification
levels
was
97.2
percent
with
a
coefficient
of
variation
of
8.3.
The
results
of
the
study
for
each
site
are
presented
in
detail
in
Table
4
of
Appendix
D.
The
results
of
the
pseudo
first
order
statistical
analysis
of
the
data
presented
in
Appendix
D
are
summarized
below
in
Table
16.
Table
16:
Cabbage
DFR
Dissipation
Data
(MRID
451917
01)
Location
App.
Rate
(lb
ai/
acre)
App.
Method
Corr.
Coeff.
Slope
(Ln
TTR
vs.
t)
[T0]
(µg/
cm
2
)
T1/
2
(days)
Day
0
(%
trans.)
CA
2.07
Groundboom
0.956
0.190
2.46
3.6
10.6
74
MRID
451143
01
(turf
transferable
residue
data):
A
TTR
study
was
conducted
at
individual
sites
in
three
states
using
the
ORETF
roller
sampling
method.
The
locations
were
in
California,
Georgia,
and
Pennsylvania.
Tall
fescue
was
the
variety
in
California
and
Pennsylvania.
Bermudagrass
was
the
variety
in
Georgia.
Field
work
took
place
over
three
week
intervals
at
each
site.
Applications
were
made
and
samples
were
collected
essentially
in
October
of
1998
in
California
and
Georgia
while
the
Pennsylvania
study
was
completed
essentially
in
May
1999.
Two
applications
were
made
7
days
apart
at
each
site.
All
applications
in
this
study
were
completed
at
a
rate
of
8.17
lb
ai/
acre.
In
California
and
Georgia,
applications
were
made
with
typical
groundboom
sprayers
using
approximately
55
and
31
gallons
of
water
per
acre,
respectively.
In
Pennsylvania,
the
applications
were
made
with
a
CO2
powered
sprayer
in
approximately
45
gallons
of
water
per
acre.
All
applications
were
made
using
Dragon
Sevin
Liquid
which
is
a
flowable
concentrate
formulation
that
contains
carbaryl
at
a
nominal
concentration
of
21
percent
by
weight
or
2
lb
ai/
gallon.
There
was
approximately
from
1
inch
up
to
2.7
inches
of
irrigation
water
on
the
day
of
the
final
application
at
each
site.
Additionally,
on
the
day
of
the
final
application,
rain
was
noted
that
ranged
in
accumulations
from
0.2
to
1.23
inches.
California
and
Pennsylvania
also
received
additional
rain
in
the
week
after
the
last
application
(i.
e.,
both
events
<
1
inch).
It
could
not
be
determined,
based
on
the
study
data,
if
the
rain
and
irrigation
events
on
the
day
of
the
last
application
at
each
site
occurred
prior
to
or
after
the
application.
Mowing
events
were
also
noted
in
the
data
except
in
Georgia
where
no
mowing
was
done.
The
other
sites
were
mowed
prior
to
the
last
application
and
at
some
point
at
least
6
days
after
the
last
application.
Triplicate
TTR
samples
were
collected
using
the
ORETF
roller
method
at
8
intervals
out
to
14
days
after
the
last
application.
All
but
two
samples
at
each
site
were
collected
during
the
1
st
week
of
the
study.
The
Limit
of
Quantitation
(LOQ)
for
carbaryl
residues
was
2
µg/
sample
which
is
equivalent
to
0.00035
µg/
cm
2
based
on
a
sample
surface
area
of
5690
cm
2
.
Average
field
recovery
values
across
levels
from
all
sites
was
greater
than
90
percent.
Additionally,
the
variability
in
the
field
recovery
data
as
defined
using
the
coefficient
of
variation
was
also
low
(<
10)
except
for
the
Georgia
site
where
the
CV
was
28.
However,
at
the
Georgia
and
Pennsylvania
sites,
the
dosespecific
recovery
value
that
closest
approximated
the
field
sample
levels
warranted
that
the
results
be
corrected
by
the
investigators
(i.
e.,
119
%
in
Georgia
and
89%
in
Pennsylvania,
respectively).
Residue
levels
were
not
corrected
for
recovery
at
the
California
site.
In
all
cases,
residue
levels
exceeded
the
LOQ
even
at
14
days
after
application.
The
results
of
the
study
for
the
California,
Georgia,
and
Pennsylvania
sites,
respectively,
are
presented
in
Tables
5,
6,
and
7
of
Appendix
D.
The
data
and
the
results
of
the
pseudo
first
order
statistical
analysis
of
the
data
presented
in
Appendix
D
are
summarized
below
in
Table
17.
75
Table
17:
TTR
Dissipation
Data
Measured
Using
ORETF
Roller
In
3
States
(MRID
451143
01)
Location
App.
Rate
(lb
ai/
acre)
App.
Method
Corr.
Coeff.
Slope
(Ln
TTR
vs.
t)
[T0]
(µg/
cm
2
)
T1/
2
(days)
Day
0
(%
trans.)
CA
8.17
Groundboom
0.971
0.543
0.927
1.3
1.
0
GA
8.17
Groundboom
0.887
0.168
1.12
4.1
1.
2
PA
8.17
CO2
0.984
0.248
1.12
2.8
1.
2
The
Georgia
data
were
used
to
calculate
short
term
and
intermediate
term
risks
because
of
the
added
persistence
(i.
e.
to
consider
a
30
day
average
residue).
Note
that
intermediate
term
risks
could
not
even
be
calculated
for
PA
and
CA
data
because
of
the
shorter
decay
time.
The
California
data
were
used
to
calculate
cancer
risks
because
of
the
quicker
dissipation
which
may
represent
more
typical
uses.
2.2.3
Occupational
Postapplication
Exposure
and
Noncancer
Risk
Estimates
The
occupational
postapplication
exposure
and
non
cancer
risk
calculations
are
presented
in
this
section.
Noncancer
risks
were
calculated
using
the
Margin
of
Exposure
(MOE)
which
is
a
ratio
of
the
body
burden
to
the
toxicological
endpoint
of
concern.
Body
burden
values
were
determined
by
first
calculating
exposures
by
considering
transferable
residue
levels
in
areas
where
people
work
(i.
e.,
the
potential
sources
of
exposure)
and
the
kinds
of
jobs
or
tasks
required
to
produce
agricultural
commodities
or
to
maintain
other
areas
such
as
golf
courses.
These
factors
are
represented
by
DFR
or
TTR
concentrations
and
transfer
coefficients.
Exposures
were
calculated
by
multiplying
these
factors
by
an
8
hour
work
day.
Exposures
are
then
normalized
by
body
weight
and
adjusted
for
dermal
absorption
to
calculate
absorbed
dose
(i.
e.,
body
burdens).
MOEs
were
then
calculated.
Postapplication
risks
diminish
over
time
because
carbaryl
residues
eventually
dissipate
in
the
environment.
As
a
result
risk
values
were
calculated
over
time
based
on
changing
residue
levels.
Dissipation
Kinetics:
The
first
step
in
the
postapplication
risk
assessment
was
to
complete
an
analysis
of
the
available
dislodgeable
foliar
and
turf
transferable
residue
(DFR)
data.
All
residue
data
generated
in
the
referenced
studies
are
summarized
in
Appendix
D
as
well
as
in
Tables
13
through
17
above.
As
discussed
in
Section
2.2.2
above,
data
from
the
4
DFR
studies
were
used
to
calculate
risks
for
all
agronomic
crop
groups.
Best
fit
DFR
levels
were
calculated
based
on
empirical
data
using
the
equation
D2
16
from
Series
875
Occupational
and
Residential
Test
Guidelines:
Group
B
Postapplication
Exposure
Monitoring
Test
Guidelines.
The
summary
of
the
available
chemical
specific
DFR
data,
presented
in
tables
13
through
17
above,
were
developed
based
on
a
semilog
regression
of
the
empirical
dissipation
data
using
a
commercial
spreadsheet
linear
regression
function.
Half
lives
were
calculated
using
the
algorithm
(T1/
2
=
Ln
2/
slope).
The
results
of
those
statistical
analyses
were
used
to
calculate
best
fit
concentrations
over
time
using
the
following
pseudo
first
order
equation:
76
Where:
Cenvir(
t)
=
dislodgeable
foliar
or
turf
transferable
residue
concentration
(
g/
cm
2
)
that
represents
the
amount
of
residue
on
the
surface
of
a
contacted
leaf
surface
that
is
available
for
dermal
exposure
at
time
(t);
Cenvir(
o)
=
dislodgeable
foliar
or
turf
transferable
residue
concentration
(
g/
cm
2
)
that
represents
the
amount
of
residue
on
the
surface
of
a
contacted
leaf
surface
that
is
available
for
dermal
exposure
at
time
(0);
e
=natural
logarithms
base
function;
PAIt
=
postapplication
interval
or
dissipation
time
(e.
g.,
days
after
treatment
or
DAT);
and
M
=
slope
of
line
generated
during
linear
regression
of
data
[ln(
Cenvir)
versus
postapplication
interval
(PAI)].
In
cases
where
no
chemical
specific
residue
dissipation
data
are
available,
the
Agency
typically
uses
a
generic
dissipation
model
to
complete
risk
calculations.
In
this
case,
the
Agency
determined
that
it
is
more
appropriate,
however,
to
extrapolate
using
carbaryl
specific
dissipation
data
in
the
risk
assessment
for
other
currently
labelled
crops
than
it
is
to
use
the
generic
dissipation
model.
This
approach
is
consistent
with
current
Agency
policies
for
generating
transferable/
dislodgeable
residue
data.
The
existing
residue
data
were
extrapolated
to
the
currently
labelled
crops
as
follows:
C
Tobacco
DFR
Data:
These
data
have
been
used
to
complete
all
assessments
for
the
crop/
activity
combinations
included
in
the
bunch/
bundle,
sugarcane,
and
vine/
trellis
agronomic
crop
groups
defined
in
the
Agency's
revised
transfer
coefficient
policy
003.
This
extrapolation
was
completed
because
of
similarities
in
application
methods
between
the
study
and
selected
crop
groups,
the
crop
canopy,
and
application
rates
(i.
e.,
between
the
study
and
current
labels).
C
Olive
DFR
Data:
These
data
have
been
used
to
complete
all
assessments
for
the
crop/
activity
combinations
included
in
all
of
the
tree
fruit
and
nut
crop
groups
defined
in
the
Agency's
revised
transfer
coefficient
policy
003.
This
extrapolation
was
completed
because
of
similarities
in
application
methods
between
the
study
and
selected
crop
groups,
the
crop
canopy,
and
application
rates
(i.
e.,
between
the
study
and
current
labels).
C
Sunflower
DFR
Data:
These
data
have
been
used
to
complete
all
assessments
for
the
crop/
activity
combinations
in
the
tall
field/
row
crop
group
defined
in
the
Agency's
revised
transfer
coefficient
policy
003.
No
extrapolation
was
required
in
this
assessment.
An
additional
consideration
was
that
the
cabbage
study
was
based
on
groundboom
application
and
not
aerial
application.
Groundboom
applications
are
thought
to
be
much
more
prevalent
in
the
overall
use
pattern
for
carbaryl.
77
C
Cabbage
DFR
Data:
These
data
have
been
used
to
complete
all
assessments
for
the
crop/
activity
combinations
included
in
the
berry,
cut
flower,
low/
medium
field
and
row,
and
all
vegetable
(i.
e.,
stem/
stalk,
brassica,
leafy,
fruiting,
cucurbits,
root)
agronomic
crop
groups
defined
in
the
Agency's
revised
transfer
coefficient
policy
003.
This
extrapolation
was
completed
because
of
similarities
in
application
methods
between
the
study
and
selected
crop
groups,
the
crop
canopy,
and
application
rates
(i.
e.,
between
the
study
and
current
labels).
C
Turf
TTR
Data:
These
data
have
been
used
to
complete
all
assessments
for
the
crop/
activity
combinations
for
the
turf
agronomic
crop
group
defined
in
the
Agency's
revised
transfer
coefficient
policy
003.
No
extrapolation
was
required
in
this
assessment.
Daily
Exposure:
The
next
step
in
the
risk
assessment
process
was
to
calculate
dermal
exposure
values
(remembering
that
inhalation
exposures
are
not
assessed
for
these
scenarios)
on
each
post
application
day
after
application
using
the
following
equation
(see
equation
D2
20
from
Series
875
Occupational
and
Residential
Test
Guidelines:
Group
B
Postapplication
Exposure
Monitoring
Test
Guidelines
and
Residential
SOP
3.2:
Postapplication
Dermal
Potential
Doses
From
Pesticide
Residues
On
Gardens):
DE(
t)
(mg/
day)
=
(TR(
t)
(µg/
cm
2
)
x
TC
(cm
2
/hr)
x
Hr/
Day)/
1000
(µg/
mg)
Where:
DE(
t)
=
Daily
exposure
or
amount
deposited
on
the
surface
of
the
skin
at
time
(t)
attributable
for
activity
in
a
previously
treated
area,
also
referred
to
as
potential
dose
(mg
ai/
day);
TR(
t)
=
Transferable
residues
that
can
either
be
dislodgeable
foliar
or
turf
transferable
residue
at
time
(t)
where
the
longest
duration
is
dictated
by
the
decay
time
observed
in
the
studies
(µg/
cm
2
);
TC
=
Transfer
Coefficient
(cm
2
/hour);
and
Hr/
day
=
Exposure
duration
meant
to
represent
a
typical
workday
(hours).
Note
that
the
(TR(
t))
input
may
represent
levels
on
a
single
day
after
application
in
the
case
of
shortterm
risk
calculations.
For
intermediate
term
calculations,
rolling
7
day
average
concentrations
were
calculated
based
on
the
applicability
of
the
toxicology
data
(i.
e.,
intermediate
term
endpoint
is
applied
to
exposures
>30
days).
In
the
limited
number
of
chronic
calculations,
a
30
day
average
was
also
used
based
on
a
likely
frequency
between
applications.
Daily
Dose
and
Margins
of
Exposure:
The
use
of
dissipation
data
and
the
manner
in
which
daily
postapplication
dermal
exposure
values
were
calculated
are
inherently
different
than
with
handler
exposures.
Once
daily
exposure
values
are
calculated,
the
calculation
of
daily
absorbed
dose
and
the
resulting
Margin
of
Exposure
values
use
the
same
algorithms
that
are
described
above
for
the
handler
exposures
(See
Section
2.1.3).
These
calculations
are
completed
for
each
day
or
appropriate
block
of
time
after
application.
78
Noncancer
Risk
Summary:
All
of
the
noncancer
risk
calculations
for
occupational
carbaryl
handlers
completed
in
this
assessment
are
included
in
Appendix
E.
The
specifics
of
each
of
table
included
in
Appendix
E
are
described
below.
A
summary
of
the
results
for
each
crop/
activity
combination
considered
for
each
timeframe
is
also
provided
below.
C
Appendix
E/
Table
1:
Inputs
For
Carbaryl
Occupational
Postapplication
Risk
Assessment
Presents
the
numerical
unit
exposure
values
and
other
factors
used
in
the
occupational
handler
risk
assessments.
C
Appendix
E/
Table
2:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Low
Berry
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
4:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Bunch/
Bundle
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
6:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Short/
Medium
Field
Row
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
8:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Tall
Field
Row
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
10:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Cut
Flower
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
[Note:
Table
10
also
contains
chronic
risk
values.]
C
Appendix
E/
Table
12:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Sugarcane
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
14:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Deciduous
Tree
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
16:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
79
Assessment
For
Evergreen
Tree
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
18:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Tree
Nut
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
20:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Turf
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
22:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Root
Vegetable
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
24:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Cucurbit
Vegetable
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
26:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Fruiting
Vegetable
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
28:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Brassica
Vegetable
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
30:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Leafy
Vegetable
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
32:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Root
Vegetable
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
34:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Vine
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
80
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
36:
Carbaryl
Occupational
Postapplication
Noncancer
Risk
Assessment
For
Nursery
Stock
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
[Note:
Table
36
also
contains
chronic
risk
values.]
It
should
be
noted
that
there
were
several
scenarios
for
which
no
appropriate
exposure
data
are
known
to
exist
or
ongoing
transfer
coefficient
studies
have
not
yet
been
submitted
(e.
g.,
ARTF
nursery
and
ornamental
data).
The
scope
of
the
Agency's
revised
policy
003
for
transfer
coefficients
should
also
be
considered
as
it
only
quantitatively
addresses
risks
where
the
transfer
coefficient
model
is
appropriate
(i.
e.,
where
foliar
contact
is
known
to
exist).
There
are
many
kinds
of
potential
exposure
pathways
that
do
not
involve
foliar
contact
that
have
not
been
addressed
in
this
risk
assessment
(as
defined
in
policy
003,
refer
to
that
document
for
a
complete
list).
The
scenarios
include:
C
Transplanting
many
crops
including
in
the
ornamental
and
forestry
industry;
C
Thinning
some
crops
such
as
hops;
C
Some
partially
mechanized
operations
that
also
involve
human
contact
(e.
g.,
cotton
harvesting
where
module
builders
and
trampers
are
used,
see
below);
C
Hand
weeding
some
crops
such
as
wheat;
C
Various
operations
with
Christmas
trees
such
as
pruning
or
baling;
and
C
Various
operations
with
nut
production
such
as
sweeping
for
harvest.
[Note:
Additional
DFR
data
on
different
crops
could
refine
exposure
and
risk
estimates.]
Mechanized
practices
can
be
divided
into
fully
mechanized
activities
that
meet
the
definition
of
"No
contact"
in
the
Agency's
Worker
Protection
Standard
(WPS)
and
mechanically
assisted
practices
with
potential
for
exposure.
In
the
case
of
fully
mechanized
activities,
the
Agency
does
not
complete
a
quantitative
exposure
assessment
but
addresses
these
types
of
potential
exposures
qualitatively
by
allowing
early
entry
as
described
in
the
WPS.
81
"A
worker
may
enter
a
treated
area
during
a
restricted
entry
interval
if
the
agricultural
employer
assures
that
both
of
the
following
are
met:
(1)
The
worker
will
have
no
contact
with
anything
that
has
been
treated
with
the
pesticide
to
which
the
restricted
entry
interval
applies
including,
but
not
limited
to,
soil,
water,
air,
or
surfaces
of
plants;
and
(2)
no
such
entry
is
allowed
until
any
inhalation
exposure
level
listed
in
the
labeling
has
been
reached
or
any
ventilation
criteria
established
by
§
170.110
(c)(
3)
or
in
the
labeling
have
been
met."
In
cases
of
partially
mechanized
activities
where
the
potential
for
exposure
exists,
the
Agency
assesses
the
resulting
exposures
similarly
to
those
resulting
from
hand
labor
activities
for
"high
exposure
potential"
activities
(i.
e.,
transfer
coefficients
are
used
to
represent
exposures
associated
with
the
activity).
Partially
mechanized
activities
with
"low
exposure
potential"
are
assessed
qualitatively.
Available
use
and
usage
information
have
been
used
to
characterize
the
predominance
of
these
activities
that
meet
the
fully
mechanized
("
No
contact")
and
the
mechanically
assisted
definitions
in
the
risk
assessment
to
allow
risk
managers
flexibility
in
their
decisions
with
regard
to
various
segments
of
the
exposed
population
for
carbaryl.
The
Agency
also
acknowledges
that
there
is
some
potential
for
exposure
because
individuals
engaged
in
fully
mechanized
activities
have
short
term
excursions
from
the
protected
area
for
various
reasons
(e.
g.,
unclogging
machinery
or
equipment
inspection
for
breakage).
In
these
cases,
the
WPS
§
170.112(
c)
Exception
for
short
term
activities
applies.
The
level
of
concern
for
all
assessments
is
established
by
the
uncertainty
factor
that
is
associated
with
a
specific
duration
of
exposure.
Uncertainty
factors
are
defined
for
occupational
exposures
under
FIFRA
and
account
for
intra
species
sensitivity
and
inter
species
extrapolation.
In
other
cases,
like
carbaryl,
additional
factors
can
also
be
required
(i.
e.,
3x)
because
a
Lowest
Observed
Adverse
Effect
Level
(i.
e.,
LOAEL)
has
been
selected
as
the
dose
level
upon
which
the
risk
assessment
is
based
and
not
on
the
No
Observed
Adverse
Effect
Level
(i.
e.,
NOAEL).
In
this
case,
three
distinct
durations
of
exposure
were
considered
for
postapplication
workers
including:
short
term
(
30
days),
intermediate
term
(>
30
days
to
several
months),
and
chronic
(essentially
every
working
day).
The
toxicological
endpoints
and
uncertainty
factors
which
have
been
applied
to
each
exposure
duration
are
those
described
in
Section
1.3/
Table
1.
The
results
for
each
exposure
duration
are
presented
separately
below.
Noncancer
short
term,
intermediate
term,
and
chronic
risks
were
calculated
for
different
crop
groups
as
described
above.
Table
18
below
provides
a
summary
of
these
risks
for
each
crop/
activity
combination
considered.
For
each
crop
group/
activity
combination,
the
short
term
MOE
value
at
the
current
REI
of
12
hours
is
presented
(i.
e.,
the
Day
0
MOE)
as
well
as
the
number
of
days
required
for
short
term
MOEs
to
reach
the
Agency's
uncertainty
factor
of
100.
Additionally,
the
intermediate
term
and
chronic
MOEs
which
have
been
calculated
using
30
day
average
exposures
based
on
the
dissipation
of
carbaryl
residues
are
also
included.
The
uncertainty
factor
for
intermediate
term
exposures
is
100
and
for
chronic
exposures
is
300.
82
Current
label
requirements
specify
12
hour
REIs.
For
all
but
the
lowest
exposure
scenarios
in
some
crops,
short
term
MOEs
are
of
concern
(i.
e.,
less
than
the
required
uncertainty
factor
of
100)
at
the
current
REI.
Generally,
short
term
MOEs
meet
or
exceed
the
Agency
uncertainty
factor
in
the
range
of
3
to
5
days
for
lower
to
medium
exposure
activities
and
from
8
to
12
days
after
application
in
most
higher
exposure
scenarios.
Intermediate
term
MOEs
are
not
of
concern
generally
for
low
to
medium
level
exposures
but
are
of
concern
for
higher
level
exposures
such
as
harvesting
in
some
crops.
Chronic
exposures
are
of
concern
for
the
cut
flower
industry
but
not
for
general
greenhouse
and
nursery
production
activities.
Table
18:
Summary
of
Carbaryl
Noncancer
Postapplication
Worker
Risks
Crop
Group
Result
Type
Exposure
Descriptor
(See
Appendix
E)
Very
Low
Low
Medium
High
Very
High
Low
Berry
ST
MOE
Day
0
NA
184
NA
49
NA
Days
For
ST
MOE
>
UF
NA
0
NA
4
NA
IT
30
Day
Avg
MOE
NA
991
NA
264
NA
Bunch/
Bundle
ST
MOE
Day
0
NA
411
32
21
NA
Days
For
ST
MOE
>
UF
NA
0
6
8
NA
IT
30
Day
Avg
MOE
NA
2365
182
118
NA
Low
/Med.
Field/
Row
Crops
ST
MOE
Day
0
NA
982
65
39
NA
Days
For
ST
MOE
>
UF
NA
0
3
5
NA
IT
30
Day
Avg
MOE
NA
5286
352
211
NA
Tall
Field/
Row
Crops
ST
MOE
Day
0
NA
245
61
25
<1
Days
For
ST
MOE
>
UF
NA
0
4
11
+30
IT
30
Day
Avg
MOE
NA
970
242
97
6
Cut
Flowers
ST
MOE
Day
0
NA
30
18
11
NA
Days
For
ST
MOE
>
UF
NA
7
9
12
NA
IT
30
Day
Avg
MOE
NA
159
99
57
NA
Chronic
MOE
NA
194
121
69
NA
Sugarcane
ST
MOE
Day
0
NA
NA
55
27
NA
Days
For
ST
MOE
>
UF
NA
NA
3
7
NA
IT
30
Day
Avg
MOE
NA
NA
315
158
NA
Decid.
Fruit
Trees
ST
MOE
Day
0
1455
146
NA
49
NA
Days
For
ST
MOE
>
UF
0
0
NA
8
NA
IT
30
Day
Avg
MOE
4450
445
NA
148
NA
Table
18:
Summary
of
Carbaryl
Noncancer
Postapplication
Worker
Risks
Crop
Group
Result
Type
Exposure
Descriptor
(See
Appendix
E)
Very
Low
Low
Medium
High
Very
High
83
Evergreen
Fruit
Trees
ST
MOE
Day
0
582
58
19
NA
NA
Days
For
ST
MOE
>
UF
0
6
17
NA
NA
IT
30
Day
Avg
MOE
1780
178
59
NA
NA
Nut
Trees
ST
MOE
Day
0
NA
175
NA
35
NA
Days
For
ST
MOE
>
UF
NA
0
NA
11
NA
IT
30
Day
Avg
MOE
NA
534
NA
107
NA
Turf/
Sod
ST
MOE
Day
0
NA
312
NA
10
NA
Days
For
ST
MOE
>
UF
NA
0
NA
14
NA
IT
30
Day
Avg
MOE
NA
1505
NA
46
NA
Root
Veg.
ST
MOE
Day
0
NA
245
49
29
NA
Days
For
ST
MOE
>
UF
NA
0
4
7
NA
IT
30
Day
Avg
MOE
NA
1322
264
159
NA
Cucurbit
Veg.
ST
MOE
Day
0
NA
147
49
29
NA
Days
For
ST
MOE
>
UF
NA
0
4
7
NA
IT
30
Day
Avg
MOE
NA
793
264
159
NA
Fruiting
Veg.
ST
MOE
Day
0
NA
147
105
74
NA
Days
For
ST
MOE
>
UF
NA
0
0
2
NA
IT
30
Day
Avg
MOE
NA
793
566
396
NA
Brassica
ST
MOE
Day
0
NA
37
18
15
NA
Days
For
ST
MOE
>
UF
NA
6
9
11
NA
IT
30
Day
Avg
MOE
NA
198
99
79
NA
Leafy
Veg.
ST
MOE
Day
0
NA
147
49
29
NA
Days
For
ST
MOE
>
UF
NA
0
4
7
NA
IT
30
Day
Avg
MOE
NA
793
264
159
NA
Stem/
stalk
Veg.
ST
MOE
Day
0
NA
137
82
41
NA
Days
For
ST
MOE
>
UF
NA
0
1
5
NA
IT
30
Day
Avg
MOE
NA
788
473
236
NA
Table
18:
Summary
of
Carbaryl
Noncancer
Postapplication
Worker
Risks
Crop
Group
Result
Type
Exposure
Descriptor
(See
Appendix
E)
Very
Low
Low
Medium
High
Very
High
84
Vine/
trellis
ST
MOE
Day
0
NA
147
74
15
7
Days
For
ST
MOE
>
UF
NA
0
2
11
14
IT
30
Day
Avg
MOE
NA
793
396
79
40
Nursery/
Ornamentals
ST
MOE
Day
0
NA
669
421
184
NA
Days
For
ST
MOE
>
UF
NA
0
0
0
NA
IT
30
Day
Avg
MOE
NA
3604
2266
991
NA
Chronic
MOE
NA
4399
2765
1210
NA
ST
=
Short
term,
IT
=
Intermediate
term,
30
Day
Avg.=
Average
exposure
level
over
30
day
interval.
NA
=
Exposure
descriptor
not
applicable
for
that
crop
group.
UF
=
uncertainty
factor
or
target
MOE
of
100.
2.2.4
Occupational
Postapplication
Exposure
and
Risk
Estimates
for
Cancer
The
occupational
exposure
and
cancer
risk
calculations
for
postapplication
workers
are
presented
in
this
section.
Cancer
risks
were
calculated
using
a
linear
low
dose
extrapolation
approach
in
which
a
Lifetime
Average
Daily
Dose
(LADD)
is
first
calculated
and
then
compared
with
a
Q1*
that
has
been
calculated
for
carbaryl
based
on
dose
response
data
in
the
appropriate
toxicology
study
(Q1*
=
8.75
x
10
4
(mg/
kg/
day)
1
).
Absorbed
average
daily
dose
(ADD)
levels
were
used
as
the
basis
for
calculating
the
LADD
values.
Section
2.1.3
above
describes
how
the
ADD
values
were
first
calculated
for
the
noncancer
MOE
calculations.
These
values
also
serve
as
the
basis
for
the
cancer
risk
estimates.
Dermal
and
inhalation
ADD
values
were
first
added
together
to
obtain
combined
ADD
values.
LADD
values
were
then
calculated
and
compared
the
Q1*
to
obtain
cancer
risk
estimates.
LADD
and
Cancer
Risk
Calculations:
The
use
of
dissipation
data
and
the
manner
in
which
daily
postapplication
dermal
exposure
values
were
calculated
are
inherently
different
than
with
handler
exposures.
Once
daily
exposure
values
are
calculated,
the
calculation
of
LADD
(Lifetime
Average
Daily
Dose)
and
the
resulting
cancer
risks
use
the
same
algorithms
that
are
described
above
for
the
handler
exposures
(See
Section
2.1.4).
To
reiterate,
occupational
carcinogenic
risks
that
are
1
x
10
6
or
lower
require
no
risk
management
action
based
on
the
1996
Barolo
memo.
For
those
chemicals
subject
to
reregistration,
the
Agency
is
to
carefully
examine
uses
with
estimated
risks
in
the
10
6
to
10
4
range
to
seek
ways
of
cost
effectively
reducing
risks.
If
carcinogenic
risks
are
in
this
range
for
postapplication
workers,
an
increase
in
time
after
application
prior
to
allowing
a
reentry
activity
would
be
warranted
as
is
commonly
applied
to
noncancer
risk
estimates.
85
Cancer
Risk
Summary
All
of
the
cancer
risk
calculations
for
carbaryl
postapplication
workers
are
included
in
Appendix
E
(various
tables).
The
specifics
of
each
of
table
included
in
Appendix
E
are
summarized
below.
C
Appendix
E/
Table
1:
Inputs
For
Carbaryl
Occupational
Postapplication
Risk
Assessment
Presents
the
numerical
unit
exposure
values
and
other
factors
used
in
the
occupational
handler
risk
assessments.
C
Appendix
E/
Table
3:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
For
Low
Berry
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
5:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
For
Bunch/
Bundle
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
7:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
For
Short/
Medium
Field
Row
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
9:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
For
Tall
Field
Row
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
11:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
For
Cut
Flower
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
13:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
For
Sugarcane
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
15:
Carbaryl
Occupational
Postapplication
Risk
Assessment
For
Deciduous
Tree
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
17:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
86
For
Evergreen
Tree
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
19:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
For
Tree
Nut
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
21:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
For
Turf
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
23:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
For
Root
Vegetable
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
25:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
For
Cucurbit
Vegetable
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
27:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
For
Fruiting
Vegetable
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
29:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
For
Brassica
Vegetable
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
31:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
For
Leafy
Vegetable
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
33:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
For
Root
Vegetable
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
35:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
For
Vine
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
87
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
E/
Table
37:
Carbaryl
Occupational
Postapplication
Cancer
Risk
Assessment
For
Nursery
Stock
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
Cancer
risks
for
private
growers
(i.
e.,
10
exposures/
year)
and
commercial
farmworkers
(i.
e.,
30
exposures/
year)
were
calculated
for
different
crop
groups
as
described
above
and
summarized
in
Table
19
below.
Within
each
crop
group,
differing
transfer
coefficients
were
used
to
represent
various
types
of
cultural
practices.
Current
label
requirements
specify
12
hour
REIs.
For
all
scenarios,
cancer
risks
are
<1x10
4
on
the
day
of
application
(i.
e.,
at
the
current
REI).
Likewise,
cancer
risks
are
<1x10
6
on
the
day
of
application
for
most
crop/
activity
scenarios
with
private
growers
and
also
for
low
to
medium
exposures
for
commercial
farmworkers.
In
fact,
risks
for
all
scenarios
were
in
the
10
6
range
in
all
but
three
scenarios
for
commercial
farmworkers
participating
in
very
high
exposure
activities
(e.
g.,
sweetcorn
handharvesting)
on
the
day
of
application.
In
these
three
cases,
risks
were
in
the
10
5
range
on
the
day
of
application.
For
private
growers,
it
takes
up
to
approximately
5
days
for
risks
to
decline
to
<1x10
6
for
crop/
activity
combinations
that
exceed
1x10
6
on
the
day
of
application.
For
commercial
farmworkers,
it
takes
up
to
approximately
8
days
for
risks
to
reach
the
target
level
of
concern
of
<1x10
6
.
The
1996
Barolo
memo
which
focused
on
cancer
risk
management
should
be
considered
in
the
interpretation
of
these
results.
Current
label
requirements
appear
to
be
adequate
for
all
postapplication
cancer
risks
if
the
10
4
range
is
used
for
risk
management.
If
the
10
6
risk
range
is
considered,
it
also
appears
that
the
current
REI
appears
adequate
to
address
cancer
risks
for
many
crop/
activity
combinations.
However,
for
higher
exposure
situations,
longer
duration
REIs
are
predicted.
In
all
cases,
REIs
predicted
based
on
cancer
risks
are
less
restrictive
or
similar
(i.
e.,
within
a
day
or
two
for
commercial
farmworkers)
than
those
predicted
based
on
the
noncancer
effects
of
carbaryl.
In
no
cases
do
cancer
risks
indicate
more
restrictive
REIs
than
for
noncancer
risks
calculated
for
the
corresponding
crop/
activity
exposure
scenario.
Table
19:
Summary
of
Carbaryl
Cancer
Postapplication
Worker
Risks
Crop
Group
Result
Type
Exposure
Descriptor
(From
Policy
003/
See
Appendix
E)
Very
Low
Low
Medium
High
Very
High
Low
Berry
Private
Grower
Day
0
Risk
NA
1.7
x
10
7
NA
6.2x
10
7
NA
Private
Grower
Days
<
1x10
6
NA
0
NA
0
NA
Com..
Farmworker
Day
0
Risk
NA
5.0
x
10
7
NA
1.9x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
NA
4
NA
Table
19:
Summary
of
Carbaryl
Cancer
Postapplication
Worker
Risks
Crop
Group
Result
Type
Exposure
Descriptor
(From
Policy
003/
See
Appendix
E)
Very
Low
Low
Medium
High
Very
High
88
Bunch/
Bundle
Private
Grower
Day
0
Risk
NA
7.4
x
10
8
9.6x
10
7
1.5x
10
6
NA
Private
Grower
Days
<
1x10
6
NA
0
0
2
NA
Com..
Farmworker
Day
0
Risk
NA
2.2
x
10
7
2.9x
10
6
4.4x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
5
8
NA
Low
/Med.
Field/
Row
Crops
Private
Grower
Day
0
Risk
NA
3.1x
10
8
4.7x
10
7
7.8x
10
7
NA
Private
Grower
Days
<
1x10
6
NA
0
0
0
NA
Com..
Farmworker
Day
0
Risk
NA
9.3x
10
8
1.4x
10
6
2.3x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
2
5
NA
Tall
Field/
Row
Crops
Private
Grower
Day
0
Risk
NA
1.2
x
10
7
5.0
x
10
7
1.2
x
10
6
2.1
x
10
5
Private
Grower
Days
<
1x10
6
NA0
0
223
Com..
Farmworker
Day
0
Risk
NA
3.7
x
10
7
1.5
x
10
6
3.7
x
10
6
8.5
x
10
5
Com..
Farmworker
Days
<
1x10
6
NA
0
3
10
31
Cut
Flowers
Private
Grower
Day
0
Risk
NA
1.0
x
10
6
1.7
x
10
6
2.9
x
10
6
NA
Private
Grower
Days
<
1x10
6
NA
0
3
6
NA
Com..
Farmworker
Day
0
Risk
NA
3.1
x
10
6
5.0
x
10
6
8.7
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
6
9
12
NA
Sugarcane
Private
Grower
Day
0
Risk
NA
NA
5.6
x
10
7
1.1
x
10
6
NA
Private
Grower
Days
<
1x10
6
NA
NA
0
1
NA
Com..
Farmworker
Day
0
Risk
NA
NA
1.7
x
10
6
3.3
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
NA
3
6
NA
Decid.
Fruit
Trees
Private
Grower
Day
0
Risk
2.1
x
10
8
2.1
x
10
7
NA
6.3
x
10
7
NA
Private
Grower
Days
<
1x10
6
0
0NA0NA
Com..
Farmworker
Day
0
Risk
6.3
x
10
8
6.3
x
10
7
NA
1.9
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
0
0NA6NA
Evergreen
Fruit
Trees
Private
Grower
Day
0
Risk
5.2
x
10
8
5.2
x
10
7
1.6
x
10
6
NA
NA
Private
Grower
Days
<
1x10
6
0
0
5
NA
NA
Com..
Farmworker
Day
0
Risk
1.6
x
10
7
1.6
x
10
6
4.7
x
10
6
NA
NA
Com..
Farmworker
Days
<
1x10
6
0
5
16
NA
NA
Nut
Trees
Private
Grower
Day
0
Risk
NA
1.7
x
10
7
NA
8.7
x
10
7
NA
Table
19:
Summary
of
Carbaryl
Cancer
Postapplication
Worker
Risks
Crop
Group
Result
Type
Exposure
Descriptor
(From
Policy
003/
See
Appendix
E)
Very
Low
Low
Medium
High
Very
High
89
Private
Grower
Days
<
1x10
6
NA
0
NA
0
NA
Com..
Farmworker
Day
0
Risk
NA
5.7
x
10
7
NA
2.6
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
NA
10
NA
Turf/
Sod
Private
Grower
Day
0
Risk
NA
8.1
x
10
8
NA
2.7
x
10
6
NA
Private
Grower
Days
<
1x10
6
NA
0
NA
2
NA
Com..
Farmworker
Day
0
Risk
NA
2.4
x
10
7
NA
8.0
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
NA
4
NA
Root
Veg.
Private
Grower
Day
0
Risk
NA
1.2
x
10
7
6.2
x
10
7
1.0
x
10
6
NA
Private
Grower
Days
<
1x10
6
NA
0
0
0
NA
Com..
Farmworker
Day
0
Risk
NA
3.7
x
10
7
1.9
x
10
6
3.1
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
4
6
NA
Cucurbit
Veg.
Private
Grower
Day
0
Risk
NA
2.1
x
10
7
6.2
x
10
7
1.0
x
10
6
NA
Private
Grower
Days
<
1x10
6
NA
0
0
0
NA
Com..
Farmworker
Day
0
Risk
NA
6.2
x
10
7
1.9
x
10
6
3.1
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
4
6
NA
Fruiting
Veg.
Private
Grower
Day
0
Risk
NA
2.1
x
10
7
2.9
x
10
7
4.1
x
10
7
NA
Private
Grower
Days
<
1x10
6
NA
0
0
0
NA
Com..
Farmworker
Day
0
Risk
NA
6.2
x
10
7
8.7
x
10
7
1.2
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
0
1
NA
Brassica
Private
Grower
Day
0
Risk
NA
8.3
x
10
7
1.7
x
10
6
2.1
x
10
6
NA
Private
Grower
Days
<
1x10
6
NA
0
3
4
NA
Com..
Farmworker
Day
0
Risk
NA
2.5
x
10
6
5.0
x
10
6
6.2
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
5
9
10
NA
Leafy
Veg.
Private
Grower
Day
0
Risk
NA
2.1
x
10
7
6.2
x
10
7
1.0
x
10
6
NA
Private
Grower
Days
<
1x10
6
NA
0
0
0
NA
Com..
Farmworker
Day
0
Risk
NA
6.2
x
10
7
1.9
x
10
6
3.1
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
4
6
NA
Stem/
stalk
Veg.
Private
Grower
Day
0
Risk
NA
2.2
x
10
7
3.7
x
10
7
7.4
x
10
7
NA
Private
Grower
Days
<
1x10
6
NA
0
0
0
NA
Table
19:
Summary
of
Carbaryl
Cancer
Postapplication
Worker
Risks
Crop
Group
Result
Type
Exposure
Descriptor
(From
Policy
003/
See
Appendix
E)
Very
Low
Low
Medium
High
Very
High
90
Com..
Farmworker
Day
0
Risk
NA
6.7
x
10
7
1.1
x
10
6
2.2
x
10
6
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
1
4
NA
Vine/
trellis
Private
Grower
Day
0
Risk
NA
2.1
x
10
7
4.1
x
10
7
2.1
x
10
6
4.1
x
10
6
Private
Grower
Days
<
1x10
6
NA0
0
4
8
Com..
Farmworker
Day
0
Risk
NA
6.2
x
10
7
1.2
x
10
6
6.2
x
10
6
1.2
x
10
5
Com..
Farmworker
Days
<
1x10
6
NA
0
1
10
13
Nursery/
Ornamentals
Private
Grower
Day
0
Risk
NA
4.5
x
10
8
7.2
x
10
8
1.7
x
10
7
NA
Private
Grower
Days
<
1x10
6
NA
0
0
0
NA
Com..
Farmworker
Day
0
Risk
NA
1.4
x
10
7
2.2
x
10
7
5.0
x
10
7
NA
Com..
Farmworker
Days
<
1x10
6
NA
0
0
0
NA
NA
=
Exposure
descriptor
not
applicable
for
that
crop
group.
2.2.5
Summary
of
Occupational
Postapplication
Risk
Concerns
and
Data
Gaps
Current
label
requirements
specify
12
hour
REIs.
For
all
but
the
lowest
exposure
scenarios
in
some
crops,
MOEs
do
not
meet
or
exceed
required
uncertainty
factors
until
several
days
after
application.
If
short
term
risks
are
considered,
MOEs
meet
or
exceed
the
Agency
uncertainty
factor
generally
in
the
range
of
3
to
5
days
after
application
for
lower
to
medium
exposure
activities
and
from
8
to
12
days
after
application
in
most
higher
exposure
scenarios.
If
intermediate
term
risks
are
considered,
MOEs
are
not
of
concern
based
on
a
30
day
average
exposures
except
for
higher
level
exposures
such
as
harvesting
in
some
crops.
Chronic
exposures
are
of
concern
for
the
cut
flower
industry
but
not
for
other
general
greenhouse
and
nursery
production
activities
based
on
the
most
recent
ARTF
data.
Cancer
risks
were
calculated
for
private
growers
and
professional
farmworkers
with
the
only
difference
being
the
annual
frequency
of
exposure
days.
Cancer
risks
for
private
growers
and
commercial
farmworkers
are
generally
in
the
10
8
to
10
6
range
on
the
day
of
application.
If
a
1x10
4
cancer
risk
is
the
target,
the
current
REI
would
be
adequate
for
all
scenarios
considered
in
the
91
assessment.
If
a
1x10
6
cancer
risk
is
used,
then
durations
longer
than
the
current
REI
should
be
considered
for
some
cases
which
are
not
considered
low
to
medium
exposures.
It
should
be
noted
that
the
cancer
risk
calculations
are
less
restrictive
than
noncancer
risk
estimates
for
the
same
scenarios
in
all
cases.
The
Agency
has
used
the
latest
information
to
complete
this
postapplication
risk
assessment
for
carbaryl.
Several
data
gaps
exist
such
as
a
lack
of
exposure
data
on
mechanized
or
partially
mechanized
cultural
practices
where
there
is
a
potential
for
exposure.
Additionally,
because
of
the
number
and
breadth
of
carbaryl
uses,
there
may
be
many
exposure
pathways
where
the
transfer
coefficient
approach
is
not
an
appropriate
model
(e.
g.,
hand
transplanting
where
no
foliar
contact
occurs)
that
have
not
been
quantitatively
addressed
due
to
a
lack
of
data.
2.2.6
Recommendations
For
Refining
Occupational
Postapplication
Risk
Assessment
To
refine
this
occupational
risk
assessment,
data
on
actual
use
patterns
including
rates,
timing,
and
the
kinds
of
tasks
that
are
required
to
produce
agricultural
commodities
and
other
products
would
better
characterize
carbaryl
risks.
Exposure
studies
for
many
cultural
practices
that
lack
data
or
that
are
not
well
represented
in
the
revised
transfer
coefficient
policy
should
also
be
considered
based
on
the
data
gaps
identified
above.
Risk
managers
should
consider
that
the
risks
associated
with
the
current
label
REI
generally
do
not
meet
Agency
risk
targets.
2.3
Occupational
Risk
Characterization
2.3.1
Handler
Characterization
The
occupational
handler
assessment
for
carbaryl
is
complex
in
that
three
different
types
of
noncancer
risk
calculations
were
required
based
on
the
recently
selected
endpoints.
The
durations
of
exposure
that
were
considered
for
noncancer
toxicity
were
short
term
(
30
days),
intermediateterm
(30
days
up
to
several
months),
and
chronic
(every
working
day).
A
complete
array
of
calculations
was
completed
for
all
identified
exposure
scenarios
using
the
short
and
intermediateterm
endpoints
because
the
Agency
believes
that
carbaryl
uses
fit
the
criteria
for
both
of
these
durations.
The
only
calculations
that
were
completed
using
the
chronic
endpoint
were
limited
and
those
associated
with
the
greenhouse
and
floriculture
industries
where
these
kinds
of
exposures
may
occur.
Cancer
risks
were
also
calculated
using
a
linear,
low
dose
extrapolation
model
(i.
e.,
Q1*)
for
both
private
growers
(i.
e.,
10
application
days
per
year)
and
for
those
who
may
more
actively
use
carbaryl
such
as
a
commercial
applicator
(i.
e.,
30
application
days
per
year).
Cancer
calculations
were
completed
as
well
for
every
scenario
that
has
been
identified
for
both
private
growers
and
commercial
applicators.
For
all
of
the
different
types
of
endpoints
selected
(except
chronic
where
a
limited
number
of
calculations
were
completed),
the
Agency
identified
exposures
that
fit
into
28
different
scenarios
which
are
defined
based
on
the
equipment
used
to
make
applications
or
the
type
of
formulation
used.
Within
each
of
these
categories,
different
application
rates
and
acres
treated
values
were
considered
to
evaluate
the
broad
range
of
applications
that
may
occur
with
each
kind
of
equipment
(e.
g.,
a
groundboom
may
be
used
for
turf
or
agriculture).
All
totaled,
128
different
crop/
rate/
acres
combinations
were
considered
within
the
28
scenarios
for
the
short
and
92
intermediate
term
toxicity
categories
plus
4
chronic
crop/
rate/
acre
combinations.
The
overall
result
is
that
4
sets
of
128
calculations
each
(516
total
calculations)
were
completed
for
occupational
carbaryl
handlers.
Finally,
it
should
be
noted
that
each
calculation
was
completed
at
different
levels
of
personal
protection
to
allow
for
a
more
informed
risk
management
decision.
Even
given
the
scope
of
the
calculations
that
have
already
been
completed,
it
is
likely
that
there
are
some
uses
of
carbaryl
that
have
not
been
quantitatively
addressed
in
this
document
either
through
lack
of
exposure
data
or
other
information
and
because
carbaryl
is
such
a
widely
used
chemical.
These
scenarios
will
be
addressed
by
the
Agency
when
they
are
identified
as
carbaryl
progresses
through
the
reregistration
process.
Readers
are
also
encouraged
to
evaluate
novel
scenarios
by
considering
the
range
of
estimates
already
completed
as
it
is
likely
that
many
uses
could
be
quantitatively
assessed
by
reviewing
those
calculations
as
a
wide
array
of
chemical
use
combinations
and
equipment
types
have
already
been
considered.
The
data
that
were
used
in
the
carbaryl
occupational
handler
risk
assessment
represent
the
best
data
and
approaches
that
are
currently
available.
While
some
of
the
data
which
have
been
used
may
not
be
of
optimal
quality,
they
represent
the
best
available
data
for
the
scenario
in
question.
In
many
cases,
the
Pesticide
Handlers
Exposure
Database
(PHED)
was
used
to
develop
the
unit
exposure
values.
The
quality
of
the
data
included
in
PHED
vary
widely
from
scenarios
that
meet
guideline
requirements
for
studies
to
others
where
a
limited
number
of
poor
quality
datapoints
are
available.
The
results
for
each
scenario
should
be
reviewed
in
the
context
of
the
quality
of
these
data.
In
addition
to
PHED,
the
Agency
used
a
number
of
studies
to
define
unit
exposure
values.
Generally,
the
quality
of
these
studies
is
excellent.
Most,
except
for
the
trigger
sprayer
data,
are
very
recent
and
based
on
the
newest
analytical
requirements
and
monitoring
techniques.
PHED
unit
exposure
values
represent
a
central
tendency
of
the
data
(i.
e.,
geometric
mean,
median
or
arithmetic
mean
depending
upon
the
distribution
of
the
data).
As
such,
the
values
based
on
the
recent
studies
also
are
measures
of
central
tendency
(e.
g.,
the
geometric
means
were
selected
from
each
study
for
assessment
purposes
in
most
cases).
Along
with
the
unit
exposure
values
used
in
the
assessment,
other
inputs
include
application
rates
and
daily
acres
treated
values.
Selected
application
rates
represent
a
range
for
each
major
market
in
which
carbaryl
is
used
including
agriculture,
turf
(lawncare,
golf
courses,
etc.),
ornamentals,
and
for
wide
area
applications
such
as
mosquito
control.
Many
application
rates
also
represent
maximum
amounts
that
are
allowed
by
the
label
for
certain
settings.
Where
available,
average
use
rates
were
also
used
to
provide
for
a
more
informed
risk
management
decision.
The
application
rates
that
were
selected
for
use
in
the
risk
assessment
were
defined
based
on
labels,
information
provided
by
the
Aventis
Corporation
at
the
September
24,
1998
SMART
Meeting
for
carbaryl,
and
based
on
various
analyses
of
carbaryl
use
patterns
completed
by
the
Agency's
Biological
and
Economic
Analysis
Division.
The
other
key
input
for
completing
handler
risk
assessments
used
for
defining
how
much
chemical
can
be
used
in
a
day
is
how
much
can
be
treated
in
a
day
which
is
generally
expressed
as
the
number
of
acres
treated
per
day.
The
values
that
were
used
for
this
parameter
represent
the
latest
Agency
thinking
on
this
issue.
In
fact,
the
Science
Advisory
Council
For
Exposure
recently
updated
the
policy
for
these
inputs
(July
2000
Exposure
SAC
Policy
9:
Standard
Values
for
Daily
Acres
Treated
in
Agriculture).
These
most
recent
values
have
been
used
for
the
calculations.
In
addition
to
the
key
sources
of
information
considered
above,
there
are
many
underlying
factors
that
may
impact
the
overall
results
of
a
risk
assessment.
For
example,
the
protection
factors
93
used
for
adding
additional
levels
of
dermal
and
respiratory
protection
may
impact
the
overall
risk
picture.
The
factors
used
in
this
assessment
by
the
Agency
are
the
ones
that
have
been
used
for
several
years.
Other
such
factors
may
include
the
fact
that
average
application
rates
have
been
generally
used
to
represent
typical
application
rates
to
calculate
ranges
of
risks
when
it
is
clear
that
the
two
values
could
differ
greatly.
The
Agency
has
taken
this
approach
because
the
data
required
to
define
typical
application
rates
within
each
crop
are
generally
unavailable.
There
are
also
exposure
monitoring
issues
that
should
be
considered.
For
example,
in
many
cases
the
data
included
in
PHED
are
based
on
the
use
of
cotton
gloves
for
hand
exposure
monitoring
which
are
thought
by
many
to
overestimate
exposure
because
they
potentially
retain
residues
more
than
human
skin
would
over
time
(i.
e.,
they
may
act
like
a
sponge
compared
to
the
actual
hand).
A
similar
issue
was
noted
with
the
carbaryl
specific
dog
grooming
study
that
used
the
handwash
approach
to
monitor
exposure
after
shampooing
several
dogs.
These
intangible
elements
of
the
risk
assessment
reflect
many
of
the
hidden
uncertainties
associated
with
exposure
data.
The
overall
impacts
of
these
uncertainties
is
hard
to
quantify.
The
factor
to
again
consider
is
that
the
Agency
used
the
best
available
data
to
complete
the
risk
assessment
for
carbaryl.
In
summary,
the
Agency
believes
that
the
risk
values
presented
in
this
occupational
assessment
represent
the
highest
quality
results
that
could
be
produced
given
the
exposure,
use,
and
toxicology
data
that
are
available.
Certainly
risk
managers
and
other
interested
parties
should
consider
the
quality
of
individual
inputs
when
interpreting
the
results
and
make
decisions
accordingly.
It
is
difficult
to
ascertain
where
on
a
distribution
the
values
which
have
been
calculated
fall
because
the
distributional
data
for
exposure,
application
rates,
acres
treated
and
many
other
parameters
are
unrefined.
The
Agency
does
believe,
however,
that
the
risks
represent
conservative
estimates
of
exposure
because
maximum
application
rates
are
coupled
with
large
acreage
estimates
to
define
risk
estimates
that
likely
fall
in
the
upper
percentiles
of
the
actual
exposure
distributions.
Additionally,
risk
estimates
are
thought
to
be
conservative
even
when
measures
of
central
tendency
are
combined
because
values
that
would
be
considered
to
be
in
the
lower
percentile
aspect
of
any
input
parameter
have
not
been
used
in
the
calculations.
2.3.2
Postapplication
Characterization
Like
the
occupational
handler
risk
assessment
discussed
above,
the
postapplication
worker
risk
assessment
for
carbaryl
is
also
complex
in
that
three
different
types
of
noncancer
risk
calculations
were
required
based
on
the
recently
selected
endpoints
along
with
cancer
risk
calculations
using
a
linear,
low
dose
extrapolation
model.
For
all
of
the
different
types
of
endpoints
selected
(except
chronic
where
a
limited
number
of
calculations
were
completed),
the
Agency
identified
exposures
that
fit
into
18
different
crop
groups
which
are
defined
essentially
based
on
the
nature
of
the
crop
where
a
work
activity
would
take
place.
Within
each
of
these
crop
groups,
ranges
of
transfer
coefficients
were
considered
to
reflect
differences
in
exposures
that
would
be
associated
with
the
variety
of
cultural
practices
that
are
required
to
produce
the
crop/
product.
All
totaled,
54
different
cultural
practices
were
considered
within
the
18
crop
groups
for
each
toxicity
category.
The
overall
result
is
that
4
sets
of
54
calculations
each
(216
plus
a
few
chronic
values)
were
completed
for
postapplication
workers.
Finally,
it
should
be
noted
that
each
calculation
was
completed
at
different
days
after
application
to
reflect
residue
dissipation
over
time
in
the
environment
and
to
allow
for
a
more
informed
risk
management
decision.
Even
given
the
scope
of
94
the
calculations
that
have
already
been
completed,
it
is
likely
that
there
are
some
uses
of
carbaryl
that
have
not
been
quantitatively
addressed
in
this
document
either
through
lack
of
exposure
data
or
other
information
and
because
carbaryl
is
such
a
widely
used
chemical.
These
scenarios
will
be
addressed
by
the
Agency
when
they
are
identified
as
carbaryl
progresses
through
the
reregistration
process.
Readers
are
also
encouraged
to
evaluate
novel
scenarios
by
considering
the
range
of
estimates
already
completed
as
it
is
likely
that
many
uses
could
be
quantitatively
assessed
by
reviewing
existing
calculations
as
a
wide
array
of
crop/
activity
combinations
have
already
been
considered.
The
data
that
were
used
in
the
carbaryl
postaapplication
worker
risk
assessment
represent
the
best
data
and
approaches
that
are
currently
available.
The
latest
Agency
transfer
coefficient
values
have
been
used
to
complete
this
assessment
including
the
recently
submitted
ARTF
studies
on
greenhouse
workers.
Most
of
the
values
in
the
current
Agency
policy
are
based
on
the
work
of
the
Agricultural
Reentry
Task
Force
(ARTF)
of
which,
Aventis
is
a
member.
The
current
Agency
policy
is
interim
in
nature
but
represents
all
of
the
data
that
have
been
submitted
by
the
ARTF
and
evaluated
by
the
Agency.
The
work
of
the
ARTF
is
still
ongoing
so
additional
data
may
become
available
to
refine
the
exposure
estimates
as
more
data
are
submitted
to
the
Agency.
Also,
it
is
possible
that
there
are
exposure
scenarios
that
have
not
been
addressed
by
the
Agency
because
the
transfer
coefficient
model
is
not
appropriate
as
there
is
little
or
no
foliar
contact
associated
with
the
activity.
There
are
also
potentially,
partially
mechanized
activities
that
could
lead
to
exposure
where
the
Agency
has
no
information.
These
will
need
to
be
carefully
considered
in
the
reregistration
process.
In
addition
to
the
exposure
inputs
for
specific
activities
(i.
e.,
transfer
coefficients),
the
Agency
used
4
carbaryl
specific
DFR
(Dislodgeable
Foliar
Residue)
dissipation
studies
and
a
single
TTR
(Turf
Transferable
Residue)
study
to
calculate
risks
for
all
postapplication
workers
in
every
region
in
the
country.
It
is
standard
practice
for
the
Agency
to
use
these
kinds
of
studies
in
this
manner
but
it
is
likely
that
additional
crop
and
region
specific
data
could
be
used
to
further
refine
the
risk
assessment.
Several
other
key
pieces
of
data
and
information
were
considered
in
the
development
of
the
postapplication
risk
values
including
use
and
usage
information
and
exposure
frequency
in
the
cancer
risk
assessment.
For
many
agricultural
crops,
the
maximum
application
rate
is
low
(e.
g.,
1.5
to
2
lb
ai/
acre)
in
many
crops.
As
a
result,
postapplication
risks
were
generally
calculated
at
maximum
rate
levels
because
of
the
already
inherent
complexity
of
the
assessment
and
because
it
is
likely
that
results
may
not
be
extremely
sensitive
to
changes
in
this
value.
In
addition
to
the
key
sources
of
information
considered
above,
there
are
many
underlying
factors
that
may
impact
the
overall
results
of
a
risk
assessment.
For
example,
subtle
differences
between
activities
in
similar
crops
within
each
of
the
18
agronomic
groups
considered
in
the
assessment
may
not
be
accurately
reflected
in
the
current
transfer
coefficient
values.
The
use
of
4
DFR
studies
to
represent
all
crops
and
all
regions
within
the
country
could
lead
to
results
that
do
not
reflect
actual
use
practices
and
conditions
in
some
parts
of
the
country.
Additionally,
the
exposure
frequency
values
that
were
used
for
private
growers
and
professional
farmworkers
tend
to
be
supported
by
available
data
but
could
be
refined
if
data
on
work
patterns
and
regional
carbaryl
use
becomes
available.
As
with
the
handler
assessment
above,
the
intangible
elements
reflect
many
of
the
hidden
uncertainties
associated
with
exposure
data.
The
overall
impacts
of
these
uncertainties
is
hard
to
quantify.
The
factor
to
again
consider
is
that
the
Agency
used
the
best
available
data
to
95
complete
the
risk
assessment
for
carbaryl.
In
summary,
the
Agency
believes
that
the
risk
values
presented
in
this
postapplication
assessment
represent
the
highest
quality
results
that
could
be
produced
given
the
exposure,
use,
and
toxicology
data
that
are
available.
Certainly
risk
managers
and
other
interested
parties
should
consider
the
quality
of
individual
inputs
when
interpreting
the
results
and
make
decisions
accordingly.
It
is
difficult
to
ascertain
where
on
a
distribution
the
values
which
have
been
calculated
fall
because
the
distributional
data
for
exposure,
residue
dissipation
and
many
other
parameters
are
unrefined.
The
Agency
does
believe,
however,
that
the
risks
represent
conservative
estimates
of
exposure
because
maximum
application
rates
are
used
to
define
residue
levels
upon
which
the
risk
calculations
are
based.
Additionally,
risk
estimates
are
thought
to
be
conservative
even
when
measures
of
central
tendency
(e.
g.,
most
transfer
coefficients
are
thought
to
be
central
tendency)
are
used
because
values
that
would
be
considered
to
be
in
the
lower
percentile
aspect
of
any
input
parameter
have
not
been
used
in
the
calculations.
3.0
Residential
and
Other
Non
Occupational
Exposures
and
Risks
It
has
been
determined
there
is
a
potential
for
exposure
in
residential
settings
during
the
application
process
for
homeowners
who
purchase
and
use
products
containing
carbaryl.
There
is
also
a
potential
for
exposure
from
entering
areas
previously
treated
with
carbaryl
such
as
lawns
where
children
might
play
or
golf
courses
and
homegardens
that
could
lead
to
exposures
for
adults.
Carbaryl
is
also
labeled
for
mosquito
adulticide
use
which
has
been
considered
in
this
assessment.
As
a
result,
risk
assessments
have
been
completed
for
both
residential
handler
and
postapplication
scenarios.
Residential
handler
exposures
and
risks
are
addressed
in
Section
3.1:
Residential
Handler
Exposures
and
Risks
while
residential
post
application
risks
for
adults
and
children
are
presented
and
summarized
in
Section
3.2:
Residential
Post
Application
Exposures
and
Risks.
The
calculated
risks
are
characterized
in
Section
3.3:
Residential
Risk
Characterization.
3.1
Residential
Handler
Exposures
and
Risks
The
Agency
uses
the
term
"Handlers"
to
describe
those
individuals
who
are
involved
in
the
pesticide
application
process.
The
agency
believes
that
there
are
distinct
tasks
related
to
applications
and
that
exposures
can
vary
depending
on
the
specifics
of
each
task
as
was
described
above
for
occupational
handlers.
Residential
handlers
are
addressed
somewhat
differently
by
the
Agency
as
homeowners
are
assumed
to
complete
all
elements
of
an
application
with
little
use
of
any
protective
equipment.
The
scenarios
that
serve
as
the
basis
for
the
risk
assessment
are
presented
in
Section
3.1.1:
Handler
Exposure
Scenarios.
The
exposure
data
and
assumptions
that
have
been
used
for
the
calculations
are
presented
in
Section
3.1.2:
Data
and
Assumptions
For
Handler
Exposure
Scenarios.
The
calculations
and
the
algorithms
that
have
been
used
for
the
noncancer
elements
of
the
risk
assessment
as
well
as
the
risk
values
are
presented
in
Section
3.1.3:
Handler
Exposure
and
Non
Cancer
Risk
Estimates
while
the
analogous
information
using
the
Q1*
for
cancer
estimates
are
presented
in
Section
3.1.4:
Handler
Exposure
and
Risk
Estimates
For
Cancer.
Section
3.1.5:
Summary
of
Risk
Concerns
and
Data
Gaps
For
Handlers
presents
the
overall
risk
picture
for
carbaryl.
Finally,
recommendations
are
presented
in
Section
3.1.6:
Recommendations
For
Refining
Residential
Handler
Risk
Assessment.
96
3.1.1
Handler
Exposure
Scenarios
Scenarios
are
again
used,
as
with
the
occupational
handler
risk
assessment
above,
to
define
risks
based
on
the
U.
S.
EPA
Guidelines
For
Exposure
Assessment
(U.
S.
EPA;
Federal
Register
Volume
57,
Number
104;
May
29,
1992).
The
purpose
of
this
section
is
to
describe
how
the
exposure
scenarios
were
defined.
Much
of
the
process
for
residential
uses
is
identical
to
that
considered
for
the
occupational
assessment
with
a
few
notable
exceptions
that
include:
°
Residential
handler
exposure
scenarios
are
only
considered
to
be
short
term
in
nature
due
to
the
episodic
uses
associated
with
homeowner
products,
as
a
result,
no
intermediate
term
or
chronic
assessments
were
completed
for
handlers;
°
A
tiered
approach
for
personal
protection
using
increasing
levels
of
PPE
is
not
used
in
residential
handler
risk
assessments,
rather
than
using
PPE,
homeowner
handler
assessments
are
completed
based
on
individuals
using
shorts
and
short
sleeved
shirts;
°
Homeowner
handlers
are
expected
to
complete
all
tasks
associated
with
the
use
of
a
pesticide
product
including
mixing/
loading
if
needed
as
well
as
the
application;
°
Label
use
rates
and
use
information
specific
to
residential
products
serve
as
the
basis
for
the
risk
calculations
as
opposed
to
the
rates
used
in
the
occupational
assessment;
and
°
Area/
volumes
of
spray
or
chemical
used
in
the
risk
assessment
are
based
on
Agency
guidance
specific
to
residential
use
patterns.
It
has
been
determined
that
exposure
to
pesticide
handlers
is
likely
during
the
residential
use
of
carbaryl
in
a
variety
of
environments
including
on
lawns,
gardens
and
ornamentals,
and
pets.
The
anticipated
use
patterns
and
current
labeling
indicate
17
major
residential
exposure
scenarios
based
on
the
types
of
equipment
and
techniques
that
can
potentially
be
used
to
make
carbaryl
applications.
The
quantitative
exposure/
risk
assessment
developed
for
residential
handlers
is
based
on
these
scenarios.
[Note:
The
scenario
numbers
correspond
to
the
tables
of
risk
calculations
included
in
the
occupational
risk
calculation
aspects
of
the
appendices.]
(1)
Garden
Uses:
Ready
to
use
Trigger
Sprayer;
(2)
Garden
Uses:
Ornamental
Duster;
(3)
Garden
Uses:
Hose
end
Sprayer;
(4)
Garden
Uses:
Low
Pressure
Handwand;
(5)
Tree/
ornamental
Uses:
Low
Pressure
Handwand;
(6)
Tree/
ornamental
Uses:
Hose
end
Sprayer;
(7)
Garden
Uses:
Backpack
Sprayer;
(8)
Lawncare
Liquid
Uses:
Hose
end
Sprayer;
(9)
Pet
(Dog
and
Cat)
Uses:
Dusting;
(10)
Pet
(Dog
and
Cat)
Uses:
Liquid
Application;
(11)
Lawncare
Granular
and
Bait
Uses:
Belly
Grinder;
(12)
Lawncare
Granular
and
Bait
Uses:
Push
type
Spreader;
97
(13)
Ornamental
and
Garden
Uses:
Granulars
and
Baits
By
Hand;
(14)
Various
Pest
Uses:
Aerosol
Cans;
(15)
Pet
(Dog
and
Cat)
Uses:
Collars;
(16)
Garden
and
Ornamental
Uses:
Sprinkler
Can;
and
(17)
Garden
and
Ornamental
Uses:
Paint
on.
3.1.2
Data
and
Assumptions
For
Handler
Exposure
Scenarios
A
series
of
assumptions
and
exposure
factors
served
as
the
basis
for
completing
the
residential
handler
risk
assessments.
Each
assumption
and
factor
is
detailed
below.
In
addition
to
these
factors,
unit
exposure
values
were
used
to
calculate
risk
estimates.
Mostly,
these
unit
exposure
values
were
taken
from
the
Pesticide
Handlers
Exposure
Database
(PHED).
In
other
cases,
chemical
specific
exposure
data
were
submitted
to
support
the
reregistration
of
carbaryl.
Both
PHED
and
the
individual
studies
are
presented
below.
[Note:
Several
of
the
assumptions
and
factors
used
for
the
assessment
are
similar
to
those
used
in
the
occupational
assessment
presented
above.
As
such,
only
factors
that
are
unique
to
the
residential
scenarios
are
presented
below.]
Assumptions
and
Factors:
The
assumptions
and
factors
used
in
the
risk
calculations
include:
C
Carbaryl
is
one
of
the
most
widely
used
pesticide
chemicals.
It
has
an
extraordinary
number
of
use
patterns
that
are
impossible
to
completely
capture
in
this
document.
As
such,
the
Agency
has
patterned
this
risk
assessment
on
a
series
of
likely
representative
scenarios
that
are
believed
to
represent
the
vast
majority
of
carbaryl
uses.
Refinements
to
the
assessment
will
be
made
as
more
detailed
information
about
carbaryl
use
patterns
become
available.
C
Exposure
factors
used
to
calculate
daily
exposures
to
handlers
were
based
on
applicable
data
if
available.
For
lack
of
appropriate
data,
values
from
a
scenario
deemed
similar
enough
by
the
assessor
might
be
used.
As
an
example,
mixer/
loader/
applicator
data
for
hose
end
sprayers
were
used
to
assess
sprinkler
can
applications.
The
nature
of
these
application
methods
are
believed
to
be
similar
enough
to
bridge
the
data.
There
were
other
instances
where
the
Agency
bridged
specific
data
to
represent
other
scenarios.
See
Appendix
G/
Table
1
for
more
details.
98
C
The
exposure
duration
(i.
e.,
years
per
lifetime)
values
used
by
the
Agency
in
the
cancer
risk
assessment
were
consistent
with
those
used
for
other
chemicals
(i.
e.,
50
years
with
home
use
chemicals
and
70
year
lifetime).
C
The
Agency
always
considers
the
maximum
application
rates
allowed
by
labels
in
its
risk
assessments
to
consider
what
is
legally
possible
based
on
the
label.
If
additional
information
such
as
average
or
typical
rates
are
available,
these
values
are
also
used
to
allow
risk
managers
to
make
a
more
informed
risk
management
decision.
Average
application
rates
were
available
from
the
SMART
meeting
and
BEAD's
QUA.
These
data
indicated
that
in
most
cases,
average
application
rates
differed
from
maximum
application
rates
on
average
by
a
factor
of
two.
In
some
other
cases,
the
average
application
rates
identified
from
the
studies
conducted
by
Aventis
were
also
used
to
define
"average
study
use
rate
values"
which
were
included
in
the
calculations
to
provide
for
a
more
informed
risk
management
decision.
°
Residential
risk
assessments
were
not
based
on
what
could
be
applied
in
a
typical
workday
like
with
the
occupational
risk
assessments
presented
above.
Instead,
the
Agency
based
calculations
on
what
would
reasonably
be
treated
by
homeowners
such
as
the
size
of
a
lawn,
or
the
size
of
a
garden.
This
information
was
used
by
the
Agency
to
define
chemical
throughput
values
for
handlers
which
in
turn
were
coupled
with
unit
exposure
values
to
calculate
risks.
The
factors
used
for
the
carbaryl
assessment
were
those
dictated
in
the
Health
Effects
Division
Science
Advisory
Committee
Policy
12:
Recommended
Revisions
To
The
Standard
Operating
Procedures
For
Residential
Exposure
Assessment
which
was
completed
on
February
22,
2001.
[Note:
Information
presented
at
SMART
meeting
did
not
include
event
specific
information
that
would
cause
the
Agency
to
use
different
values
than
those
presented
below.]
The
following
daily
volumes
handled
and
area
treated,
excerpted
from
the
policy
and
used
in
each
residential
scenario,
include:
°
1
container
of
each
ready
to
use
non
pet
product
including
garden
dusts,
trigger
sprayers
and
aerosol
cans
(scenarios
for
25
and
50
%
used
of
the
total
product
volume
were
also
presented
for
the
trigger
sprayer
and
garden
dust
scenarios
to
allow
for
a
more
informed
risk
management
decision);
°
½
container
of
each
ready
to
use
pet
products
including
dusts
and
liquid
shampoos;
°
1
pet
collar;
°
100
gallons
of
finished
spray
output
for
hose
end
sprayers;
°
5
gallons
when
mixing/
loading/
applying
liquids
with
a
backpack
sprayer
or
a
low
pressure
handwand
sprayer,
value
was
also
used
for
sprinkler
can
applications;
°
1
gallon
of
paint
on
solution
for
ornamental/
garden
uses;
°
20,000
square
feet
is
used
to
represent
the
surface
area
treated
for
broadcast
applications
to
lawns;
°
1000
square
feet
is
used
as
the
treatment
area
for
many
spot
applications
in
lawns,
gardens,
and
ornamentals
(this
value
used
as
appropriate
when
application
rates
were
based
on
a
square
foot
basis
for
spot
type
treatments);
and
°
5
mounds
per
day
treated
for
fire
ant
applications.
99
°
At
the
September
24,
1998
SMART
Meeting
with
the
Agency,
the
Aventis
Corporation
supplied
data
focused
on
the
use
patterns
for
carbaryl.
The
information
presented
at
that
meeting
supports
the
inputs
used
by
the
Agency
in
this
risk
assessment.
Several
key
factors
have
been
summarized
below
for
residential
users
of
carbaryl:
°
Carbaryl
accounted
for
approximately
9
percent
of
the
residential
insecticide
market
and
was
ranked
4
th
on
the
list
behind
the
pyrtethroids,
chlorpyrifos,
and
diazinon
[Note:
This
may
be
different
in
2001
because
of
registration
changes
for
other
chemicals];
°
The
maximum
turf
application
rate
noted
was
8
lb
ai/
acre
by
lawns/
landscape
services
on
residential
turf;
°
Insect
control
on
vegetables
(~
58%
of
users),
annuals
(~
50%
of
users),
lawns
(~
35%
of
users),
trees/
shrubs
(~
34%
of
users)
account
for
the
majority
of
uses
for
carbaryl;
°
Pet
uses
account
for
~13
percent
of
users;
°
The
annual
frequency
for
use
was
reported
to
be
1
(34
th
%tile)
to
2
times
per
year
(60
th
%tile)
and
5
times
per
year
(84
th
%tile);
°
Aphids,
ants,
fire
ants,
fleas,
and
slugs/
snails
are
the
most
predominantly
controlled
pests
by
residential
carbaryl
users
(~
30%
down
to
15%
of
uses,
respectively);
°
Most
(75%)
of
vegetable
gardens
treated
with
carbaryl
are
<800
ft
2
but
~8
percent
are
between
800
and
1500
ft
2
,
~9
percent
are
between
1500
and
5000
ft
2
,
and
~6
percent
are
greater
than
5000
ft
2
;
°
Tomatoes,
peppers,
cucumbers,
beans,
and
fruit
trees
represent
the
most
treated
garden
plants;
°
Most
(82%)
of
flower
gardens
treated
with
carbaryl
are
<500
ft
2
but
~10
percent
are
between
500
and
1200
ft
2
,
and
~8
percent
are
greater
than
1200
ft
2
;
°
Roses,
shrubs,
and
certain
annuals
represent
the
most
treated
flowering/
ornamental
plants;
and
°
Dusts
(65%)
and
liquid
concentrate
(25%)
account
for
most
carbaryl
sales
in
the
residential
annual
market
of
~2.2M
pounds
active
ingredient
per
year.
°
The
Aventis
Corporation
provided
data
for
freqency
of
annual
use
among
residential
applicators
that
had
been
used
to
calculate
cancer
risks
for
adults
in
the
general
population.
These
data
show
that
the
50
th
percentile
is
between
1
and
2
uses
per
year
so
all
cancer
risks
have
been
calculated
based
on
a
single
use
event
per
year.
Risk
managers
should
consider
this
element
in
their
interpretation
of
the
overall
results.
For
example,
there
might
be
a
smaller
population
of
more
frequent
users
(e.
g.,
84
th
%tile
=
5
times
per
year)
that
maintain
high
frequencies
of
use
over
their
lifetimes
which
is
critical
for
consideration
in
cancer
risk
assessment.
Longitudinal
data,
however,
were
not
available
to
establish
that
such
populations
definitively
exist.
Additionally,
the
Agency
calculated
the
number
of
days
exposure
per
year
that
would
be
required
to
exceed
a
risk
level
of
1.0x10
6
to
illustrate
an
exposure
limit
in
order
to
allow
for
a
more
informed
risk
management
decision.
°
For
pet
collar
uses,
Agency
policy
outlined
in
the
Residential
SOPs,
was
used
to
define
the
exposure
level
associated
with
putting
the
collar
on
an
animal.
The
SOPs
specify
1
percent
of
the
total
active
ingredient
in
the
collar
is
considered
equal
to
the
exposure.
100
°
For
turf,
the
maximum
application
rate
that
was
indicated
at
the
SMART
meeting
was
8
lb
ai/
acre
even
though
current
labels
allow
for
applications
by
homeowners
at
up
to
11
lb
ai/
acre
for
Lock
n
load
type
packages
and
9
lb
ai/
acre
for
granulars.
Residential
Handler
Exposure
Studies:
The
unit
exposure
values
that
were
used
in
this
assessment
were
based
on
three
carbaryl
specific
residential
handler
studies
which
quantified
exposures
during
pet
treatments
with
a
dust;
applications
to
gardens
using
a
ready
to
use
trigger
sprayer,
a
dust,
a
hose
end
sprayer,
and
a
low
pressure
handwand;
and
during
applications
to
trees
using
a
low
pressure
handwand
and
a
hose
end
sprayer.
Two
other
studies
completed
by
the
Outdoor
Residential
Exposure
Task
Force
and
the
Pesticide
Handler
Exposure
Database
(PHED,
Version
1.1
August
1998)
were
also
used
as
sources
of
surrogate
information.
For
pet
collars
only,
a
scenario
from
the
SOPs
For
Residential
Exposure
Assessment
not
based
on
monitoring
data
was
used
to
calculate
exposures.
A
citation
for
each
study
as
well
as
a
brief
summary
is
provided
below.
[Note:
PHED
is
described
above
in
Section
2.1.2,
refer
to
that
section
for
further
information.]
°
Carbaryl
Applicator
Exposure
Study
During
Application
of
Sevin
®
5
Dust
to
Dogs
By
the
Non
Professional.
Agrisearch
Study
No.
1517.
EPA
MRID
444399
01.
Report
date
August
22,
1997;
Authors:
D.
Larry
Merricks,
Ph.
D.,
Sponsor:
Rhone
Poulenc
Ag
Company.
°
Carbaryl
Mixer/
Loader/
Applicator
Exposure
Study
during
Application
of
RP
2
Liquid
(21%)
Sevin
®
Ready
to
Use
Insect
Spray
or
Sevin
®
10
Dust
to
Home
Garden
Vegetables.
Agrisearch
Study
No.
1519.
EPA
MRID
444598
01.
Report
dated
August
22,
1998,
Author;
Thomas
C.
Mester,
Ph.
D.,
Sponsor:
Rhone
Poulenc
Ag
Company.
°
Carbaryl
Mixer/
Loader/
Applicator
Exposure
Study
during
Application
of
RP
2
Liquid
(21%)
to
Fruit
Trees
and
Ornamental
Plants.
Agrisearch
Study
No.
1518.
MRID
445185
01.
Report
dated
January
23,
1998.
Author
D.
Larry
Merricks,
Ph.
D.,
Sponsor:
Rhone
Poulenc
Ag
Company.
°"
Integrated
Report
For
Evaluation
of
Potential
Exposures
To
Homeowners
and
Professional
Lawncare
Operators
Mixing,
Loading,
and
Applying
Granular
And
Liquid
Pesticides
To
Residential
Lawns
"
EPA
MRID
449722
01;
October
10,
1999;
Author:
Dennis
R.
Klonne,
Ph.
D.;
Sponsor:
Outdoor
Residential
Exposure
Task
Force;
EPA
Review
by
Gary
Bangs
(April
30,
2001).
[Note
to
Chemical
Review
Manager:
Appendix
F
contains
the
data
excerpted
from
each
of
the
carbaryl
specific
studies
which
were
recently
completed
by
the
Aventis
Corporation.
Some
of
the
handler
exposure
data
used
in
this
assessment
are
from
the
Outdoor
Residential
Exposure
Task
Force
(ORETF).
There
is
no
data
compensation
issue
associated
with
the
use
of
the
ORETF
data
in
the
carbaryl
risk
assessment
because
the
Aventis
Corporation,
the
registrant
for
carbaryl,
is
a
member
of
the
ORETF.
The
task
force
recently
submitted
proprietary
data
to
the
Agency
on
hoseend
sprayers
and
push
type
granular
spreaders
for
residential
handlers
(MRID
#
44972201).
The
ORETF
data
were
used
in
this
assessment
in
place
of
PHED
data.
The
ORETF
data
were
designed
to
replace
the
present
PHED
data
with
higher
confidence,
higher
quality
data
that
contains
more
101
replicates
than
the
PHED
data
for
those
scenarios.
Finally,
the
Agency
identified
several
occupational
exposure
studies
from
the
literature
by
investigators
such
as
Kurtz
and
Bode.
These
data
have
not
been
used
by
the
Agency
quantitatively
in
this
assessment
because
of
several
issues
but
were
qualitatively
considered
and
also
used
to
confirm
the
currently
used
exposure
data.]
MRID
44439901
(Carbaryl
homeowner
dog
dusting
study):
The
objective
of
the
study
was
to
measure
homeowner
dermal
and
respiratory
exposure
to
carbaryl
while
dusting
3
dogs
for
fleas
using
Sevin®
5
Dust.
The
dogs
were
from
a
local
facility
and
varied
in
size
and
fur
length.
The
product
was
supplied
to
the
handlers
in
1
lb.
Ortho
Sevin
®
5
Dust
canisters.
The
handlers
opened
the
can,
shook
the
product
onto
the
dogs
coat
and
rubbed
the
dust
into
the
fur.
The
first
replicate
consisted
of
each
applicator
applying
dust
to
3
dogs
of
varying
size
with
chemical
resistant
gloves
on.
The
first
set
of
monitoring
devices,
handwashes
and
face/
neck
wipes
and
air
monitors
were
taken
and
replaced
with
a
clean
set
of
dosimeters
on
the
same
person
for
the
second
set
of
replicates.
The
second
replicate
was
the
same
handler
applying
Ortho
®
Sevin
®
5
Dust
without
gloves
on
3
dogs.
A
total
of
40
replicates
were
collected,
20
replicates
with
gloves
and
20
replicates
without
gloves.
Each
replicate
wore
inner
and
outer
dosimeters
to
simulate
skin
and
clothing
respectively.
The
inner
dosimeter
layer
consisted
of
100
percent
cotton
long
leg
and
long
sleeved
underwear
worn
beneath
the
outer
dosimeter
of
long
leg
and
long
sleeved
100
percent
cotton
work
clothes.
Each
dosimeter
was
cut
into
six
separate
dermal
body
part
samples
(i.
e.,
lower
and
upper
arms,
lower
and
upper
legs,
front
and
back
torso)
for
a
total
of
480
dermal
samples
for
handlers
with
gloves
and
without
gloves.
The
cloth
dosimeter
parts
(inner
and
outer),
handwashes,
face/
neck
wipes
and
air
monitoring
devices
frozen,
sent
to
a
laboratory
and
analyzed
for
carbaryl.
The
amount
of
product
used
to
dust
3
dogs
averaged
65.3
grams
or
3.51
grams
ai.
On
average
to
dust
3
dogs
required
7
minutes.
Field
fortification
recoveries
for
passive
dosimeters
averaged
>90
percent
for
inner
and
outer
dosimeters.
Face
and
neck
wipe
fortifications
average
87.6
percent.
Inhalation
OVS
tube
field
fortification
averaged
100
percent,
however
one
sample
of
30
was
damaged
in
shipping
and
one
day
does
not
have
field
fortification
data.
Dosimeter
field
fortification
results
that
were
>90
percent
were
not
adjusted,
therefore
only
the
face
and
neck
wipe
were
adjusted
for
field
recovery.
Laboratory
method
validation
for
each
matrix
fell
within
the
acceptable
range
of
70
to
120
percent.
Storage
stability
tests
were
done
and
acceptable.
Unit
exposure
values
were
calculated
using
the
data
from
the
study
and
a
commercial
spreadsheet
program.
The
study
reported
the
total
exposure
to
carbaryl
as
only
the
inner
dosimeter.
Since
this
is
a
residential
product,
inner
dosimeter
upper
arm
and
upper
legs,
front
and
back
torso
were
combined
with
the
outer
dosimeter
lower
arms
and
lower
legs
to
account
for
the
handler
wearing,
a
short
sleeved
shirt,
short
pants
and
no
gloves.
The
exposures
that
were
calculated
were
normalized
by
the
amount
of
chemical
used
and
by
the
body
weight
of
the
dogs
treated
by
the
individual
applicators.
For
each
calculation,
the
arithmetic
mean,
geometric
mean,
and
median
of
the
data
are
presented
in
Table
20
below.
No
analyses
were
completed
with
these
data
to
ascertain
the
exact
type
of
distribution.
The
Agency
typically
uses
the
best
fit
values
from
the
Pesticide
Handlers
Exposure
Database
which
are
representations
of
the
central
tendency.
Considering
the
102
standard
practice,
the
Agency
will
use
the
geometric
mean
for
risk
assessment
purposes.
The
other
values
are
presented
for
comparative
purposes.
Table
20:
Unit
Exposure
Values
Obtained
From
Carbaryl
Homeowner
Dog
Dusting
Study
(MRID
444399
01)
Type
(mg
exp./
lb
ai
handled)
(mg
exp./
lb
treated
dog)
Dermal
Inhalation
Dermal
Inhalation
Applications
with
a
dust
to
dogs
Arith.
Mean
3800
33
0.0080
5.0
x
10
12
Geo.
Mean
3300
25
0.0052
3.8
x
10
12
Median
3300
27
0.0057
3.9
x
10
12
MRID
44459801
(Carbaryl
application
to
vegetables
study):
The
data
collected
reflect
the
dermal
and
respiratory
exposure
of
homeowners
mixing,
loading
and
applying
RP
2
Liquid
(21%),
a
carbaryl
end
use
product.
Applications
were
made
by
volunteers
to
two
18
foot
rows
of
tomatoes
and
one
18
foot
row
of
cucumber.
The
only
test
field
was
located
in
Florida.
For
this
study,
RP
2
Liquid
(21%)
exposures
were
monitored
using
hose
end
sprayers
and
low
pressure
handwand
sprayers.
Exposures
to
Sevin
®
10
Dust,
using
a
separate
duster
device
that
required
transfer
from
the
package
and
Sevin
®
Ready
To
Use
Insect
Spray
(RTU)
in
a
trigger
sprayer
package
were
also
monitored.
Exposure
for
each
spray
method/
product
combination
was
monitored
using
40
handlers
(replicates).
Of
the
40
replicates
per
spray
method/
product
combination,
20
wore
household
latex
gloves
and
20
performed
tasks
without
gloves.
The
20
dust
product
replicates
loaded
the
dusters
and
applied
without
gloves
only.
Each
replicate
opened
the
end
use
product,
added
it
to
the
application
implement
(except
the
RTU
product),
adjusted
the
setting
and
applied
it
to
the
vegetable
rows.
After
application
to
the
vegetable
rows,
dosimeters
were
collected.
Inhalation
exposure
was
monitored
with
personal
air
sampling
pumps
with
OVS
tubes
attached
to
the
shirt
collar
in
the
breathing
zone.
Dermal
exposure
was
assessed
by
extraction
of
carbaryl
from
inner
and
outer
100
percent
cotton
dosimeters,
face/
neck
wipes,
and
glove
and
hand
washes.
The
inner
and
outer
dosimeters
were
segmented
into:
lower
and
upper
arms,
lower
and
upper
legs,
front
and
back
torso.
Field
fortification
recoveries
for
passive
dosimeters
averaged
84.3
percent
for
inner
and
77.7
percent
for
outer
dosimeters.
Face
and
neck
wipe
fortifications
average
84.8
percent.
Handwash
and
Inhalation
OVS
tube
field
fortification
averaged
>90
percent.
Inner
and
outer
dosimeter
and
face
and
neck
wipe
residues
were
adjusted
for
field
fortification
results.
Handwash
and
inhalation
residues
were
not
adjusted.
Laboratory
method
validation
for
each
matrix
fell
within
the
acceptable
range
of
70
to
120
percent.
The
limit
of
quantitation
(LOQ)
was
1.0
µg/
sample
for
all
media
except
the
inhalation
monitors
where
the
LOQ
was
0.01
µg/
sample.
The
limit
of
detection
(LOD)
was
0.5
µg/
sample
for
all
media
except
the
inhalation
monitors
where
the
LOQ
was
0.005
µg/
sample.
Dermal
exposure
was
determined
by
adding
the
values
from
the
bare
hand
rinses,
face/
neck
wipes
to
the
outer
dosimeter
lower
legs
and
lower
arms
plus
the
inner
dosimeter
front
and
rear
torso,
upper
legs,
lower
legs,
lower
arms,
and
upper
arms.
This
accounts
for
the
residential
handler
wearing
short
sleeved
shirt
and
short
pants.
Unit
exposures
for
each
application
method
are
103
presented
below
in
Table
21.
Table
21:
Unit
Exposure
Values
Obtained
From
Carbaryl
Homeowner
Vegetable
Treatment
Study
(MRID
444598
01)
Scenario
Monitored
Dermal
Unit
Exposure
(mg
ai/
lb
handled)
Inhalation
Unit
Exposure
(µg
ai
/lb
handled)
Geometric
Mean
Median
Geometric
Mean
Median
Hand
Held
Pump
Spray
38
35
9
11
Hose
End
Sprayer
34
31
2
2.3
Ready
to
Use
Spray
54
53
67
34
Duster
148
140
870
1200
MRID
44518501
(Carbaryl
application
to
trees
and
shrubs
study):
Applications
of
Sevin
Liquid®
Carbaryl
insecticide
[RP
2
liquid
(21%)]
were
made
by
volunteers
to
two
young
citrus
trees
and
two
shrubs
in
each
replicate
that
was
monitored
in
the
study.
The
test
field
was
located
only
in
Florida.
Twenty
(20)
replicates
were
monitored
using
hose
end
sprayer
(Ortho®
DIAL
or
Spray®
hose
end
sprayer),
and
20
replicates
were
monitored
using
hand
held
pump
sprayers
(low
pressure
handwands).
Each
replicate
opened
the
end
use
product,
added
it
to
the
hose
end
sprayer
or
hand
held
pump
and
then
applied
it
to
the
trees
and
shrubs.
After
application
to
two
trees
and
two
shrubs
dosimeters
were
collected.
Inhalation
exposure
was
monitored
with
personal
air
sampling
pumps
with
OVS
tubes
attached
to
the
shirt
collar
in
the
breathing
zone.
Dermal
exposure
was
assessed
by
extraction
of
carbaryl
from
inner
and
outer
100
percent
cotton
dosimeters.
The
inner
and
outer
dosimeters
were
segmented
into:
lower
and
upper
arms,
lower
and
upper
legs,
front
and
back
torso.
No
gloves
were
worn
therefore
hand
exposure
was
assessed
with
400
ml
handwash
with
0.01
percent
Aerosol
OT
75
sodium
dioctyl
sulfosuccinate
(OTS).
One
hundred
(100)
percent
cotton
handkerchiefs
wetted
with
25
ml
OTS
were
used
to
wipe
face
and
neck
to
determine
exposure.
Field
fortification
recoveries
for
passive
dosimeters
averaged
88.3
percent
for
inner
and
76.2
percent
for
outer
dosimeters.
Face
and
neck
wipe
fortifications
average
82.5
percent.
Handwash
and
inhalation
OVS
tube
field
fortification
averaged
>90
percent.
Inner
and
outer
dosimeter
and
face
and
neck
wipe
residues
were
adjusted
for
field
fortification
results.
Handwash
and
inhalation
residues
were
not
adjusted.
Laboratory
method
validation
for
each
matrix
fell
within
the
acceptable
range
of
70
to
120
percent.
The
limit
of
quantitation
(LOQ)
was
1.0
µg/
sample
for
all
media
except
the
inhalation
monitors
where
the
LOQ
was
0.01
µg/
sample.
The
limit
of
detection
(LOD)
was
0.5
µg/
sample
for
all
media
except
the
inhalation
monitors
where
the
LOQ
was
0.005
µg/
sample.
For
use
in
reregistration
documents,
the
dermal
exposure
was
calculated
by
adding
the
values
from
the
hand
rinses,
face/
neck
wipes
to
the
outer
dosimeter
lower
legs
and
lower
arms
plus
the
inner
dosimeter
front
and
rear
torso,
upper
legs,
lower
legs,
lower
arms,
and
upper
arms.
This
accounts
for
the
residential
handler
wearing
short
sleeved
shirt
and
short
pants.
The
results
are
104
summarized
in
Table
22
below.
Table
22:
Unit
Exposure
Values
Obtained
From
Carbaryl
Homeowner
Ornamental
Treatment
Study
(MRID
44518501)
Scenario
Monitored
Hose
End
Pump
Sprayer
Applied
(lb
ai)
Dermal
Exposure
(mg
ai/
lb
handled)
Inhalation
(ug
ai/
lb
handled)
Applied
(lb
ai)
Dermal
Exposure
(mg
ai/
lb
handled)
Inhalation
(ug
ai/
lb
handled)
Geo.
Mean
0.033
39
2.5
0.
017
56
6.5
Median
0.026
44
2.6
0.
018
49
4.3
EPA
MRID
449722
01
(ORETF
Handler
Studies):
A
report
was
submitted
by
the
ORETF
(Outdoor
Residential
Exposure
Task
Force)
that
presented
data
in
which
the
application
of
various
products
used
on
turf
by
homeowners
and
lawncare
operators
(LCOs)
was
monitored.
All
of
the
data
submitted
in
this
report
were
completed
in
a
series
of
studies.
The
two
studies
that
monitored
homeowner
exposure
scenarios
used
a
granular
spreader
(ORETF
Study
OMA003)
and
a
hose
end
sprayer
(ORETF
Study
OMA004)
are
summarized
below.
OMA003:
A
total
of
30
volunteer
test
subjects
were
monitored
using
passive
dosimetry
(inner
and
outer
whole
body
dosimeters,
hand
washes,
face/
neck
wipes,
and
personal
inhalation
monitors).
Each
test
subject
carried,
loaded,
and
applied
two
25
lb
bags
of
fertilizer
(0.89%
active
ingredient)
with
a
rotary
type
spreader
to
a
lawn
(a
turf
farm
in
North
Carolina)
covering
10,000
ft
2
(one
bag
to
each
of
the
two
5000
ft
2
test
plots).
Application
to
each
subplot
continued
until
the
hopper
was
empty.
Each
participant
also
disposed
of
the
empty
bags
at
the
end
of
the
replicate.
The
target
application
rate
was
2
lb
ai/
acre
(actual
rate
achieved
was
about
1.9
lb
ai/
acre).
The
average
application
time
was
22
minutes,
including
loading
the
rotary
push
spreader
and
disposing
of
the
empty
bags.
Approximately
0.45
lb
ai
was
handled
in
each
replicate.
Dermal
exposure
was
measured
using
inner
and
outer
whole
body
dosimeters,
hand
washes,
face/
neck
washes,
and
personal
air
monitoring
devices
with
OVS
tubes.
Overall,
residues
were
highest
on
the
upper
and
lower
leg
portions
of
the
dosimeters.
Inhalation
exposure
was
calculated
using
an
assumed
respiratory
rate
of
17
Lpm
for
light
work
(NAFTA,
1999),
the
actual
sampling
time
for
each
individual,
and
the
pump
flow
rate.
All
results
were
normalized
for
lb
a.
i.
handled.
All
fortified
samples
and
field
samples
collected
on
the
same
study
day
were
stored
frozen
and
analyzed
together,
eliminating
the
need
for
storage
stability
determination.
Seventyseven
percent
(77%)
of
the
face
and
neck
washes
were
below
the
level
of
quantitation
(LOQ)
for
dacthal,
and
ten
percent
(10%)
of
the
air
samples
were
also
at
or
below
the
LOQ.
Where
results
were
less
than
the
reported
LOQ,
½
LOQ
value
was
used
for
calculations,
and
no
recovery
corrections
were
applied.
Lab
spike
recoveries
for
all
matrices
were
in
the
range
of
83
99
percent.
Mean
field
fortification
recoveries
over
the
four
study
days
for
each
fortification
level
ranged
from
83
to
97
percent.
OMA004:
Dermal
and
inhalation
exposures
were
estimated
using
passive
dosimetry
techniques
(biological
monitoring
data
were
not
collected).
A
total
of
60
replicates
were
monitored
using
30
test
subjects
(two
replicates
each)
during
applications
to
residential
lawns
in
Frederick,
Maryland.
Thirty
applicator
replicates
were
monitored
using
a
ready
to
105
use
(RTU)
product
(Bug
B
Gon)
packaged
in
a
32
fl.
oz.
screw
on
container.
These
containers
were
attached
to
garden
hose
ends.
An
additional
30
mixer/
loader/
applicator
replicates
were
monitored
using
Diazinon
Plus
also
packaged
in
32
fl.
oz.
plastic
bottles.
This
product
required
the
test
subjects
to
pour
the
product
into
dial
type
sprayers
(DTS)
that
were
attached
to
garden
hose
ends.
A
nominal
application
rate
of
4
lb
ai/
acre
was
used
for
all
replicates.
Each
replicate
monitored
the
test
subject
treating
5,000
ft
2
of
turf
and
handling
a
total
of
0.5
lb
ai/
replicate.
The
average
time
per
replicate
was
75
minutes.
Dermal
and
inhalation
exposure
were
measured
using
inner
and
outer
whole
body
dosimeters
(long
pants
and
long
sleeved
shirt
over
long
underwear),
hand
washes,
face/
neck
washes,
and
personal
air
monitoring
devices.
Lab
fortified
dosimeters
had
recoveries
of
87
103
percent;
field
fortified
dosimeters
had
a
mean
range
of
79
104
percent
recovery,
with
very
little
variance.
The
study
results
are
corrected
for
field
recoveries
using
the
correction
factor
for
the
level
of
fortification
closest
to
the
field
result.
The
route
specific
exposure
data
(dermal
and
inhalation)
from
both
studies
were
lognormally
distributed.
Therefore,
the
geometric
mean
of
the
dermal
and
inhalation
data
should
be
used
for
exposure
assessments.
The
unit
exposure
values
are
presented
in
Table
23
below.
Table
23:
Unit
Exposure
Values
Obtained
From
ORETF
Homeowner
Studies
(MRID
449722
01)
Scenario
(mg
exp./
lb
ai
handled)
Dermal
Inhalation
Homeowner
Push
Granular
Spreader
0.68
0.00091
Homeowner
Hose
End
11.0
0.
016
All
unit
exposure
values
are
geometric
means.
Exposure
values
represent
individuals
wearing
shorts
and
short
sleeved
shirts.
Hose
end
sprayer
data
for
mix
your
own
(not
the
locking/
no
contact
package)
considered.
3.1.3
Residential
Handler
Exposure
and
Non
Cancer
Risk
Estimates
The
residential
handler
exposure
and
non
cancer
risk
calculations
are
presented
in
this
section.
Noncancer
risks
were
calculated
using
the
Margin
of
Exposure
(MOE)
as
described
in
Section
2.1.3.
Much
of
the
process
for
residential
uses
is
identical
to
that
considered
for
the
occupational
assessment
with
a
few
notable
exceptions
as
described
above
in
Section
3.1.1
(e.
g.,
all
are
short
term
exposures
and
people
wear
shorts
and
short
sleeved
shirts).
The
other
major
difference
with
residential
risk
assessments
is
that
the
uncertainty
factor
which
defines
the
level
of
risk
concern
also
has
the
additional
FQPA
safety
factor
applied.
In
the
case
of
carbaryl,
in
January
and
February
2002
meetings
of
the
FQPA
Safety
Factor
Committee,
it
was
decided
that
the
factor
should
be
reduced
to
1
based
on
the
recently
revised
FQPA
SFC
standard
operating
procedures.
Therefore,
the
overall
uncertainty
factor
applied
to
carbaryl
for
residential
handler
risk
assessments
is
100
which
is
based
on
the
FQPA
safety
factor
of
1
along
with
the
100
applied
for
inter
species
extrapolation,
intra
species
sensitivity,
and
the
use
of
a
NOAEL
for
risk
assessment.
Noncancer
Risk
Summary:
All
of
the
noncancer
risk
calculations
for
occupational
carbaryl
handlers
completed
in
this
assessment
are
included
in
Appendix
G
(Tables
1
3).
The
106
specifics
of
each
of
table
included
in
Appendix
G
are
described
below.
A
brief
summary
of
the
results
for
each
exposure
scenario
is
also
provided
below.
C
Appendix
G/
Table
1:
Sources
of
Exposure
Data
Used
In
The
Carbaryl
Homeowner
Handler
Exposure
and
Risk
Calculations
Describes
the
sources
and
quality
of
the
exposure
data
used
in
all
of
the
residential
handler
calculations.
C
Appendix
G/
Table
2:
Input
Parameters
For
Carbaryl
Homeowner
Handler
Exposure
and
Risk
Calculations
Presents
the
numerical
unit
exposure
values
and
other
factors
used
in
the
residential
handler
risk
assessments.
C
Appendix
G/
Table
3:
Carbaryl
MOEs
Attributable
To
Combined
Homeowner
Handler
Dermal
and
Inhalation
Exposures
Risk
values
are
presented
for
each
exposure
scenario
considered
in
the
assessment.
Exposures
represent
individuals
wearing
shortsleeved
shirts
and
short
pants.
The
data
submitted
by
the
Aventis
Corporation
accompanied
by
the
other
data
used
by
the
Agency
have
provided
a
basic
broad
overview
of
the
uses
of
carbaryl
around
a
residential
environment
(i.
e.,
the
database
is
fairly
complete).
As
indicated
above,
however,
it
is
likely
that
carbaryl
can
be
used
in
a
myriad
of
ways
that
have
not
been
identified
in
this
assessment
because
of
different
pests
or
types
of
application
equipment.
The
Agency
will
consider
risks
from
these
additional
scenarios
as
data
become
available.
It
should
also
be
noted
that
there
were
many
other
scenarios
where
medium
to
low
PHED
quality
data
were
used
to
complete
the
assessment.
Data
quality
should
be
considered
in
the
interpretation
of
the
uncertainties
associated
with
each
risk
value
presented.
Short
term
risks
for
residential
handlers
(intermediate
term
scenarios
are
not
thought
to
exist
because
of
the
sporadic
nature
of
applications
by
homeowners)
are
presented
in
Table
24
(Appendix
G/
Table
3
summarized
below
for
the
convenience
of
the
reader).
For
most
scenarios
(40
out
of
52),
risks
are
not
of
concern
because
MOEs
exceed
the
required
uncertainty
factor
of
100.
As
expected,
the
scenarios
for
which
MOEs
do
not
meet
or
exceed
100
have
a
relatively
high
unit
exposure
associated
with
them
or
the
amount
of
chemical
used
over
a
day
is
relatively
high
(based
on
high
application
rates
and/
or
high
amounts
of
area
treated).
The
use
of
dusts
in
gardens
and
for
pet
grooming
along
with
some
liquid
sprays
on
ornamentals
appear
to
be
the
most
problematic
scenarios.
Unlike
the
occupational
handler
scenarios,
the
use
of
different
levels
of
personal
107
protective
clothing
and
equipment
is
not
considered
for
residential
handlers
because
of
a
lack
of
availability,
training,
and
maintenance.
[Note:
Scenarios
where
MOEs
are
still
of
concern
(i.
e.,
<100)
for
are
highlighted
in
the
table.]
TABLE
24
CARBARYL
MOEs
ATTRIBUTABLE
TO
COMBINED
SHORT
TERM
HOMEOWNER
HANDLER
DERMAL
AND
INHALATION
EXPOSURES
SCEN.
SCEN.
DESCRIPTOR
CROP
TYPE
OR
TARGET
EXPOSURE
FACTORS
DERMAL
MOEs
INHALATION
MOEs
COMBINED
MOEs
APPL.
RATE
(lb
ai/
unit)
BASIS
FOR
RATE
(defines
unit
treated)
TREATED
UNITS
ACTIVE
USED
(lb
ai/
event)
1
Garden:
Ready
to
Use
Trigger
Sprayer
(MRID
444598
01)
Vegetables/
Ornamentals
0.003
32
oz
bottle
0.126
%
(769
977)
0.25
0.00075
34567.9
1393034.8
33730.9
Vegetables/
Ornamentals
0.003
32
oz
bottle
0.126
%
(769
977)
0.5
0.0015
17284.0
696517.4
16865.4
Vegetables/
Ornamentals
0.003
32
oz
bottle
0.126
%
(769
977)
1
0.003
8642.0
348258.7
8432.7
Average
Study
Use
Rate
0.012
(lb
ai/
1000
ft2)
1
0.012
2160.5
87064.7
2108.2
2
Garden/
Ornamental
Dust
(MRID
444598
01)
Vegetables/
Ornamentals
0.4
4
lb
bottle
10%
(239
1513)
0.25
0.1
94.6
804.6
84.6
Vegetables/
Ornamentals
0.4
4
lb
bottle
10%
(239
1513)
0.5
0.2
47.3
402.3
42.3
Vegetables/
Ornamentals
0.4
4
lb
bottle
10%
(239
1513)
1
0.4
23.6
201.1
21.2
Average
Study
Use
Rate
0.079
(lb
ai/
1000
ft2)
1
0.079
119.7
1018.5
107.1
3
Garden:
Hose
End
(MRID
444598
01)
General
Use
(2%
soln)
0.02
(lb
ai/
gal
spray
applied)
100
2
20.6
17500.0
20.6
Perimeter
Nuisance
Pest
0.19
(lb
ai/
1000
ft2)
1
0.19
216.7
184210.5
216.5
Vegetables
0.012
(lb
ai/
1000
ft2)
1
0.012
3431.4
2916666.7
3427.3
Vegetables/
Ornamentals
0.023
(lb
ai/
1000
ft2)
1
0.023
1790.3
1521739.1
1788.2
Vegetables
0.047
(lb
ai/
1000
ft2)
1
0.047
876.1
744680.9
875.1
Average
Study
Use
Rate
0.26
(lb
ai/
1000
ft2)
1
0.26
158.4
134615.4
158.2
Fire
Ant
0.0075
(lb
ai/
gal
spray)
100
0.75
54.9
46666.7
54.8
4
Garden:
Low
Pressure
Handwand
(MRID
444598
01)
General
Use
(2%
soln)
0.02
(lb
ai/
gal
spray
applied)
5
0.1
368.4
77777.8
366.7
Perimeter
Nuisance
Pest
0.19
(lb
ai/
1000
ft2)
1
0.19
193.9
40935.7
193.0
Vegetables
0.012
(lb
ai/
1000
ft2)
1
0.012
3070.2
648148.1
3055.7
Vegetables/
Ornamentals
0.023
(lb
ai/
1000
ft2)
1
0.023
1601.8
338164.3
1594.3
Vegetables
0.047
(lb
ai/
1000
ft2)
1
0.047
783.9
165484.6
780.2
Average
Study
Use
Rate
0.083
(lb
ai/
1000
ft2)
1
0.083
443.9
93708.2
441.8
Fire
Ant
0.0075
(lb
ai/
gal
spray)
5
0.0375
982.5
207407.4
977.8
TABLE
24
CARBARYL
MOEs
ATTRIBUTABLE
TO
COMBINED
SHORT
TERM
HOMEOWNER
HANDLER
DERMAL
AND
INHALATION
EXPOSURES
SCEN.
SCEN.
DESCRIPTOR
CROP
TYPE
OR
TARGET
EXPOSURE
FACTORS
DERMAL
MOEs
INHALATION
MOEs
COMBINED
MOEs
APPL.
RATE
(lb
ai/
unit)
BASIS
FOR
RATE
(defines
unit
treated)
TREATED
UNITS
ACTIVE
USED
(lb
ai/
event)
108
5
Trees/
Ornamentals:
Low
Pressure
Handwand
(MRID
445185
01)
Ornamental
0.023
(lb
ai/
1000
ft2)
1
0.176
1087.0
468227.4
1084.4
Pome
Fruit
0.07
(lb
ai/
1000
ft2)
1
0.07
357.1
153846.2
356.3
Nuts/
Stone
Fruit
0.12
(lb
ai/
1000
ft2)
1
0.12
208.3
89743.6
207.9
Citrus
0.176
(lb
ai/
1000
ft2)
1
0.023
142.0
61188.8
141.7
Average
Study
Use
Rate
0.0047
(lb
ai/
gal,
17g
ai/
4
min
at
2GPM)
5
0.024
1063.8
458265.1
1061.4
6
Trees/
Ornamentals:
Hose
End
Sprayer
(MRID
445185
01)
Ornamental
0.023
(lb
ai/
1000
ft2)
1
0.176
1560.8
1217391.3
1558.8
Pome
Fruit
0.07
(lb
ai/
1000
ft2)
1
0.07
512.8
400000.0
512.2
Nuts/
Stone
Fruit
0.12
(lb
ai/
1000
ft2)
1
0.12
299.1
233333.3
298.8
Citrus
0.176
(lb
ai/
1000
ft2)
1
0.023
204.0
159090.9
203.7
Average
Study
Use
Rate
0.005
(lb
ai/
gal
spray)
100
0.5
71.8
56000.0
71.7
7
Garden:
Backpack
Sprayer
(PHED)
General
Use
(2%
soln)
0.02
(lb
ai/
gal
spray
applied)
5
0.1
2745.1
23333.3
2456.1
Perimeter
Nuisance
Pest
0.19
(lb
ai/
1000
ft2)
1
0.19
1444.8
12280.7
1292.7
Vegetables
0.012
(lb
ai/
1000
ft2)
1
0.012
22875.8
194444.4
20467.8
Vegetables/
Ornamentals
0.023
(lb
ai/
1000
ft2)
1
0.023
11935.2
101449.3
10678.9
Vegetables
0.047
(lb
ai/
1000
ft2)
1
0.047
5840.6
49645.4
5225.8
Average
Study
Use
Rate
0.083
(lb
ai/
1000
ft2)
1
0.083
3307.3
28112.5
2959.2
Fire
Ant
0.0075
(lb
ai/
gal
spray)
5
0.0375
7320.3
62222.2
6549.7
8
Lawn
Care:
Hose
End
Sprayer
(MRID
449722
01/
ORETF
OMA
004)
Lawn
(broadcast)
0.25
(lb
ai/
1000
ft2)
20
5
25.5
875.0
24.7
Lawn
(spot)
0.25
(lb
ai/
1000
ft2)
1
0.25
509.1
17500.0
494.7
9
Dusting
Dog
(MRID
444399
01)
Average
Study
Use
Rate
0.0026
(lb
ai/
dog)
1
0.0026
163.2
1076.9
141.7
Dog
(10%
&
1/
2
of
2
lb)
0.1
(lb
ai/
dog)
1
0.1
4.2
28.0
3.7
Dog
(5%
&
1/
2
of
2
lb)
0.05
(lb
ai/
dog)
1
0.05
8.5
56.0
7.4
10
Dogs:
Liquid
Application
Dog
(0.5%
&
1/
2
of
6
oz)
0.001
(lb
ai/
dog)
1
0.001
14000000.0
No
Data
No
Data
11
Granular
&
Baits
Lawn
Care:
Belly
Grinder
Lawn
(spot)
0.21
(lb
ai/
1000
ft2)
1
0.21
60.6
5376.3
59.9
Lawn
(spot)
0.1
(lb
ai/
1000
ft2)
1
0.1
127.3
11290.3
125.9
12
Granular
&
Baits
Lawn
Care:
Push
Type
Spreader
(MRID
449722
01/
ORETF
OMA
003)
Lawn
(broadcast)
0.21
(lb
ai/
1000
ft2)
20
4.2
490.2
18315.0
477.4
Lawn
(broadcast)
0.1
(lb
ai/
1000
ft2)
20
2
1029.4
38461.5
1002.6
13
Granulars
&
Baits
By
Hand
Ornamentals
and
Gardens
0.21
(lb
ai/
1000
ft2)
1
0.21
15.5
713.8
15.2
14
Aerosol
Various
0.005
(0.5
%
ai
in
soln./
1
pt
can)
16
0.08
79.5
364.6
65.3
15
Collar
Dog
0.013
(16
%
ai
per
1.3
oz
collar)
1
0.013
10769230.8
No
Data
No
Data
16
Sprinkler
Can
(Source:
Scenario
6)
Ornamentals
(2%
Soln)
0.02
(2%
soln
used
ad
libitum)
5
0.1
359.0
280000.0
358.5
TABLE
24
CARBARYL
MOEs
ATTRIBUTABLE
TO
COMBINED
SHORT
TERM
HOMEOWNER
HANDLER
DERMAL
AND
INHALATION
EXPOSURES
SCEN.
SCEN.
DESCRIPTOR
CROP
TYPE
OR
TARGET
EXPOSURE
FACTORS
DERMAL
MOEs
INHALATION
MOEs
COMBINED
MOEs
APPL.
RATE
(lb
ai/
unit)
BASIS
FOR
RATE
(defines
unit
treated)
TREATED
UNITS
ACTIVE
USED
(lb
ai/
event)
109
17
Ornamental
Paint
On
Ornamentals
(2%
Soln)
0.02
(2%
soln
used
ad
libitum)
1
0.02
304.3
12323.9
297.0
3.1.4
Residential
Handler
Exposure
and
Risk
Estimates
for
Cancer
The
residential
handler
exposure
and
cancer
risk
calculations
are
presented
in
this
section.
Cancer
risks
were
calculated
using
a
linear,
low
dose
extrapolation
approach
(Q1*)
using
the
same
formula
as
described
above
in
Section
2.1.4.
In
addition
to
the
cancer
risk
estimates
for
an
annual
frequency
of
1
time
per
year,
the
number
of
days
of
exposure
per
year
required
to
get
a
1x10
6
cancer
risk
have
been
calculated.
In
this
calculation,
the
1x10
6
cancer
risk
limit
was
divided
by
the
calculated
cancer
risk
for
each
scenario
for
a
single
day
of
exposure.
Much
of
the
process
for
residential
uses
is
identical
to
that
considered
for
the
occupational
assessment
with
a
few
notable
exceptions
as
described
above
in
Section
3.1.1
(e.
g.,
all
are
short
term
exposures
and
people
wear
shorts
and
short
sleeved
shirts).
The
other
major
difference
with
residential
risk
assessments
is
that
the
annual
frequency
of
use
is
lower
for
homeowners
(i.
e.,
1
day
use
per
year
has
been
used
to
complete
the
calculations).
Cancer
Risk
Summary
All
of
the
cancer
risk
calculations
for
residential
carbaryl
handlers
completed
in
this
assessment
are
included
in
Appendix
G
(Table
4).
The
specifics
of
this
table
as
well
as
a
brief
summary
of
the
results
for
each
exposure
scenario
is
also
provided
below.
C
Appendix
G/
Table
4:
Carbaryl
Cancer
Risks
Attributable
To
Combined
Homeowner
Handler
Dermal
and
Inhalation
Exposures
Presents
cancer
risks
for
combined
dermal
and
inhalation
exposures
considered
in
the
assessment
(i.
e.,
1
time/
year).
Additionally,
the
number
of
days
of
exposure
that
are
allowed
per
year
(i.
e.,
up
to
a
1x10
6
cancer
risk
limit)
are
also
presented.
Table
25
presents
the
quantitative
risks
associated
with
each
scenario
considered
in
the
assessment.
For
all
but
one
scenario
(i.
e.,
treating
dogs
with
½
bottle
of
10
percent
dust),
cancer
risks
are
less
than
1x10
6
(most
are
in
the
10
8
or
10
10
range)
when
a
single
application
per
year
is
evaluated.
This
table
also
includes
the
allowable
number
of
days
exposure
per
year.
There
are
5
scenarios
where
5
days
or
less
of
exposure
per
year
is
allowable.
These
results
should
be
considered
in
conjunction
with
the
use
and
usage
information
supplied
by
the
Aventis
Corporation
that
indicates
the
50
th
percentile
annual
frequency
of
use
is
between
1
and
2
uses
per
year
and
that
5
uses
per
year
is
at
the
84
th
percentile
(see
Section
3.1.2:
Data
and
Assumptions
For
Handler
Exposure
Scenarios
above).
As
with
the
noncancer
risks,
the
use
of
dusts
in
gardens
and
for
pet
grooming
along
with
some
liquid
sprays
on
ornamentals
appear
to
be
the
most
problematic
scenarios.
[Note:
Scenarios
where
risks
are
still
of
concern
(i.
e.,
<1x10
6
)
for
are
highlighted
in
the
table.]
110
TABLE
25:
CARBARYL
CANCER
RISKS
ATTRIBUTABLE
TO
COMBINED
HOMEOWNER
HANDLER
DERMAL
AND
INHALATION
EXPOSURES
SCEN.
SCEN.
DESCRIPTOR
CROP
TYPE
OR
TARGET
EXPOSURE
FACTORS
CANCER
RISK
ALLOWED
DAYS/
YR
APPL.
RATE
(lb
ai/
unit)
BASIS
FOR
RATE
(defines
unit
treated)
TREATED
UNITS
ACTIVE
USED
(lb
ai/
event)
1
Garden:
Ready
to
Use
Trigger
Sprayer
(MRID
444598
01)
Vegetables/
Ornamentals
0.003
32
oz
bottle
0.126
%
(769
977)
0.25
0.00075
1.27e
10
>365
Vegetables/
Ornamentals
0.003
32
oz
bottle
0.126
%
(769
977)
0.5
0.
0015
2.54e
10
>365
Vegetables/
Ornamentals
0.003
32
oz
bottle
0.126
%
(769
977)
1
0.
003
5.08e
10
>365
Average
Study
Use
Rate
0.012
(lb
ai/
1000
ft2)
1
0.
012
2.03e
09
>365
2
Garden/
Ornamental
Dust
(MRID
444598
01)
Vegetables/
Ornamentals
0.4
4
lb
bottle
10%
(239
1513)
0.25
0.1
4.
81e
08
21
Vegetables/
Ornamentals
0.4
4
lb
bottle
10%
(239
1513)
0.5
0.
2
9.62e
08
10
Vegetables/
Ornamentals
0.4
4
lb
bottle
10%
(239
1513)
1
0.
4
1.92e
07
5
Average
Study
Use
Rate
0.079
(lb
ai/
1000
ft2)
1
0.
079
3.80e
08
26
3
Garden:
Hose
End
(MRID
444598
01)
General
Use
(2%
soln)
0.02
(lb
ai/
gal
spray
applied)
100
2
2.
11e
07
5
Perimeter
Nuisance
Pest
0.19
(lb
ai/
1000
ft2)
1
0.
19
2.
01e
08
50
Vegetables
0.012
(lb
ai/
1000
ft2)
1
0.
012
1.27e
09
>365
Vegetables/
Ornamentals
0.023
(lb
ai/
1000
ft2)
1
0.
023
2.43e
09
>365
Vegetables
0.047
(lb
ai/
1000
ft2)
1
0.
047
4.97e
09
201
Average
Study
Use
Rate
0.26
(lb
ai/
1000
ft2)
1
0.
26
2.
75e
08
36
Fire
Ant
0.
0075
(lb
ai/
gal
spray)
100
0.75
7.93e
08
13
4
Garden:
Low
Pressure
Handwand
(MRID
444598
01)
General
Use
(2%
soln)
0.02
(lb
ai/
gal
spray
applied)
5
0.
1
1.18e
08
85
Perimeter
Nuisance
Pest
0.19
(lb
ai/
1000
ft2)
1
0.
19
2.
25e
08
45
Vegetables
0.012
(lb
ai/
1000
ft2)
1
0.
012
1.42e
09
>365
Vegetables/
Ornamentals
0.023
(lb
ai/
1000
ft2)
1
0.
023
2.72e
09
>365
Vegetables
0.047
(lb
ai/
1000
ft2)
1
0.
047
5.56e
09
180
Average
Study
Use
Rate
0.083
(lb
ai/
1000
ft2)
1
0.
083
9.82e
09
102
Fire
Ant
0.
0075
(lb
ai/
gal
spray)
5
0.
0375
4.44e
09
225
5
Trees/
Ornamentals:
Low
Pressure
Handwand
(MRID
445185
01)
Ornamental
0.023
(lb
ai/
1000
ft2)
1
0.
176
4.01e
09
250
Pome
Fruit
0.
07
(lb
ai/
1000
ft2)
1
0.
07
1.
22e
08
82
Nuts/
Stone
Fruit
0.12
(lb
ai/
1000
ft2)
1
0.
12
2.
09e
08
48
Citrus
0.176
(lb
ai/
1000
ft2)
1
0.
023
3.06e
08
33
Average
Study
Use
Rate
0.0047
(lb
ai/
gal,
17g
ai/
4
min
at
2GPM)
5
0.
47
4.
09e
09
244
TABLE
25:
CARBARYL
CANCER
RISKS
ATTRIBUTABLE
TO
COMBINED
HOMEOWNER
HANDLER
DERMAL
AND
INHALATION
EXPOSURES
SCEN.
SCEN.
DESCRIPTOR
CROP
TYPE
OR
TARGET
EXPOSURE
FACTORS
CANCER
RISK
ALLOWED
DAYS/
YR
APPL.
RATE
(lb
ai/
unit)
BASIS
FOR
RATE
(defines
unit
treated)
TREATED
UNITS
ACTIVE
USED
(lb
ai/
event)
111
6
Trees/
Ornamentals:
Hose
End
Sprayer
(MRID
445185
01)
Ornamental
0.023
(lb
ai/
1000
ft2)
1
0.
176
2.79e
09
359
Pome
Fruit
0.
07
(lb
ai/
1000
ft2)
1
0.
07
8.
49e
09
118
Nuts/
Stone
Fruit
0.12
(lb
ai/
1000
ft2)
1
0.
12
1.
45e
08
69
Citrus
0.176
(lb
ai/
1000
ft2)
1
0.
023
2.13e
08
47
Average
Study
Use
Rate
0.005
(lb
ai/
gal
spray)
100
0.025
6.06e
08
16
7
Garden:
Backpack
Sprayer
(PHED)
General
Use
(2%
soln)
0.02
(lb
ai/
gal
spray
applied)
5
0.
1
1.66e
09
>365
Perimeter
Nuisance
Pest
0.19
(lb
ai/
1000
ft2)
1
0.
19
3.
15e
09
317
Vegetables
0.012
(lb
ai/
1000
ft2)
1
0.
012
1.99e
10
>365
Vegetables/
Ornamentals
0.023
(lb
ai/
1000
ft2)
1
0.
023
3.81e
10
>365
Vegetables
0.047
(lb
ai/
1000
ft2)
1
0.
047
7.79e
10
>365
Average
Study
Use
Rate
0.083
(lb
ai/
1000
ft2)
1
0.
083
1.38e
09
>365
Fire
Ant
0.
0075
(lb
ai/
gal
spray)
5
0.
0375
6.22e
10
>365
8
Lawn
C
are:
H
ose
E
nd
Sprayer
(MRID
449722
01/
ORETF
OMA
004)
Lawn
(broadcast)
0.25
(lb
ai/
1000
ft2)
20
5
1.
73e
07
6
Lawn
(spot)
0.
25
(lb
ai/
1000
ft2)
1
0.
25
8.
64e
09
116
9
Dusting
Dog
(MRID
444399
01)
Average
Study
Use
Rate
0.0026
(lb
ai/
dog)
1
0.
0026
2.82e
08
35
Dog
(10%
&
1/
2
of
2
lb)
0.1
(lb
ai/
dog)
1
0.
1
1.09e
06
1
Dog
(5%
&
1/
2
of
2
lb)
0.05
(lb
ai/
dog)
1
0.
05
5.
43e
07
2
10
Dogs:
Liquid
Application
Dog
(0.
5%
&
1/
2
of
6
oz)
0.001
(lb
ai/
dog)
1
0.
001
3.11e
13
>365
11
Granular
&
Baits
Lawn
Care:
Belly
Grinder
Lawn
(spot)
0.
21
(lb
ai/
1000
ft2)
1
0.
21
7.
21e
08
14
Lawn
(spot)
0.
1
(lb
ai/
1000
ft2)
1
0.
1
3.43e
08
29
12
Granular
&
Baits
Lawn
Care:
Push
Type
Spreader
(MRID
449722
01/
ORETF
OMA
003)
Lawn
(broadcast)
0.21
(lb
ai/
1000
ft2)
20
4.2
8.
97e
09
112
Lawn
(broadcast)
0.1
(lb
ai/
1000
ft2)
20
2
4.
27e
09
234
13
Granulars
&
Baits
By
Hand
Ornamentals
and
Gardens
0.21
(lb
ai/
1000
ft2)
1
0.
21
2.
83e
07
4
14
Aerosol
Various
0.005
(0.
5
%
ai
in
soln./
1
pt
can)
16
0.08
5.94e
08
17
15
Collar
Dog
0.013
(16
%
ai
per
1.3
oz
collar)
1
0.
013
4.04e
13
>365
16
Sprinkler
Can
(Source:
Scenario
6)
Ornamentals
(2%
Soln)
0.02
(2%
soln
used
ad
libitum)
5
0.
1
1.21e
08
82
17
Ornamental
Paint
On
Ornamentals
(2%
Soln)
0.02
(2%
soln
used
ad
libitum)
1
0.
02
1.
44e
08
69
112
3.1.5
Summary
of
Risk
Concerns
and
Data
Gaps
for
Handlers
Generally,
MOEs
associated
with
most
scenarios
(40
of
52
considered)
are
not
of
concern
because
they
exceed
the
Agency's
uncertainty
factors
for
noncancer
risk
assessments
(i.
e.,
100
uncertainty
factor).
The
scenarios
of
concern
involve
the
use
of
dusts
in
gardens
and
on
pets
and
some
liquid
sprays
on
gardens.
Cancer
risks
for
most
scenarios
are
in
the
10
8
to
10
10
range
although
there
is
one
scenario
where
the
risks
slightly
exceed
1x10
6
(dusting
dogs
1.09x10
6
).
It
should
be
noted
that
there
are
5
scenarios
where
the
allowable
days
per
year
of
exposure
is
less
than
or
equal
to
5
which
should
be
considered
in
conjunction
with
the
use/
usage
data
from
Aventis
that
indicates
5
uses
per
year
is
the
84
th
percentile.
The
database
for
carbaryl
is
fairly
complete
compared
to
many
other
chemicals.
Recent,
high
quality
data
generated
by
the
Aventis
Corporation
and
the
ORETF,
of
which
Aventis
is
a
member,
have
been
used
to
address
the
key
residential
uses
of
carbaryl
on
lawns,
flower
and
vegetable
gardens,
and
pets.
Use
and
usage
inputs
also
appear
to
be
essentially
consistent
with
the
information
provided
by
the
Aventis
Corporation
at
the
1998
SMART
meeting.
No
key
data
gaps
have
been
identified
by
the
Agency
at
this
time
for
residential
handlers.
However,
it
is
likely
that
there
are
scenarios
that
remain
unaddressed
by
the
Agency
at
this
time
due
to
a
lack
of
data
or
other
meta
information.
The
Agency
will
address
other
appropriate
scenarios
as
they
are
identified.
3.1.6
Recommendations
For
Refining
Residential
Handler
Risk
Assessment
In
order
to
refine
this
residential
risk
assessment,
more
data
on
actual
use
patterns
including
rates,
timing,
and
areas
treated
would
better
characterize
carbaryl
risks.
Exposure
studies
for
many
equipment
types
that
lack
data
or
that
are
not
well
represented
in
PHED
(e.
g.,
because
of
low
replicate
numbers
or
data
quality)
should
also
be
considered
based
on
the
data
gaps
identified
above
and
based
on
a
review
of
the
quality
of
the
data
used
in
this
assessment.
3.2
Residential
Postapplication
Exposures
and
Risks
The
Agency
uses
the
term
"postapplication"
to
describe
exposures
to
individuals
that
occur
as
a
result
of
being
in
an
environment
that
has
been
previously
treated
with
a
pesticide.
Carbaryl
can
be
used
in
many
areas
that
can
be
frequented
by
the
general
population
including
residential
areas
(e.
g.,
home
lawns
and
gardens),
parks,
athletic
fields,
and
golf
courses.
As
a
result,
individuals
can
be
exposed
by
entering
these
areas
if
they
have
been
previously
treated.
Carbaryl
can
also
be
used
on
companion
animals
which
can
lead
to
exposures
by
contact
with
the
treated
animal.
Finally,
carbaryl
can
also
be
used
as
a
mosquito
adulticide
which
can
result
in
exposures
to
the
general
population
because
it
involves
wide
area,
ultra
low
volume
spraying
in
residential
areas.
The
Agency
generically
refers
to
these
exposures
as
"residential"
in
nature.
Another
definition
could
be
any
exposures
that
do
not
occur
as
a
result
of
employment
or
exposures
to
the
general
population.
The
scenarios
that
serve
as
the
basis
for
the
risk
assessment
are
presented
in
Section
3.2.1:
Residential
Postapplication
Exposure
Scenarios.
The
exposure
data
and
assumptions
that
have
been
used
for
the
calculations
are
presented
in
Section
3.2.2:
Data
and
Assumptions
For
Residential
Postapplication
Exposure
Scenarios.
The
calculations
and
the
algorithms
that
have
been
used
for
the
noncancer
elements
of
the
risk
assessment
as
well
as
the
calculated
risk
values
are
presented
in
Section
3.2.3:
Residential
Postapplication
Exposure
and
Noncancer
Risk
Estimates
113
while
the
analogous
information
using
the
Q1*
for
cancer
estimates
are
presented
in
Section
3.2.4:
Residential
Postapplication
Exposure
and
Risk
Estimates
For
Cancer.
Section
3.2.5:
Summary
of
Residential
Postapplication
Risk
Concerns
and,
Data
Gaps
presents
the
overall
risk
picture
for
carbaryl.
Finally,
recommendations
are
presented
in
Section
3.2.6:
Recommendations
For
Refining
Residential
Postapplication
Risk
Assessment.
3.2.1
Residential
Postapplication
Exposure
Scenarios
Carbaryl
uses
are
extremely
varied
and
include
home
gardens,
ornamentals,
turf
(golf
courses
and
lawns)
and
companion
animals
(e.
g.,
on
dogs
and
cats).
Carbaryl
also
has
more
limited
uses
that
were
considered
including
as
a
mosquito
adulticide
in
residential
areas
and
for
Ghost/
Mud
shrimp
control
in
Washington.
As
a
result,
a
wide
array
of
individuals
of
varying
ages
can
potentially
be
exposed
when
they
do
activities
in
areas
that
have
been
previously
treated
or
have
contact
with
treated
companion
animals.
The
Agency
is
concerned
about
these
kinds
of
exposures.
The
purpose
of
this
section
is
to
explain
how
postapplication
exposure
scenarios
were
developed
for
each
residential
setting
where
carbaryl
can
be
used.
Exposure
scenarios
can
be
thought
of
as
ways
of
categorizing
the
kinds
of
exposures
that
occur
related
to
the
use
of
a
chemical.
The
use
of
scenarios
as
a
basis
for
exposure
assessment
is
very
common
as
described
in
the
U.
S.
EPA
Guidelines
For
Exposure
Assessment
(U.
S.
EPA;
Federal
Register
Volume
57,
Number
104;
May
29,
1992).
The
processes
that
were
used
by
the
Agency
in
the
development
of
scenarios
for
occupational
exposure
assessment
(Section
2.2.1
above)
are
essentially
the
same
as
those
used
for
residential
exposure
patterns.
There
are
key
differences,
however,
in
the
residential
exposure
assessment
that
include
exposures
were
calculated
for
children
of
differing
ages
as
well
as
adults;
non
dietary
ingestion
exposures
were
calculated
(i.
e.,
soil
ingestion,
hand/
object
to
mouth);
a
dermal
"hug"
approach
has
been
used
instead
of
transfer
coefficients
to
calculate
exposures
to
companion
animals;
exposures
to
swimmers,
oyster
harvesters,
and
children
playing
on
a
beach
were
calculated;
and
cancer
risks
were
not
calculated
for
children
per
Agency
policy.
The
Agency
relies
on
a
standardized
approach
for
completing
residential
risk
assessments
that
is
based
on
current
carbaryl
labels
and
guidance
contained
in
the
following
five
documents:
°
Series
875,
Residential
and
Residential
Exposure
Test
Guidelines:
Group
B
Postapplication
Exposure
Monitoring
Test
Guidelines
(V
5.4,
Feb.
1998)
This
document
provides
general
risk
assessment
guidance
and
criteria
for
analysis
of
residue
dissipation
data.
°
Standard
Operating
Procedures
For
Residential
Exposure
Assessment
(Dec.
1997)
This
document
provides
the
overarching
guidance
for
developing
residential
risk
assessments
including
scenario
development,
algorithms,
and
values
for
inputs.
°
Science
Advisory
Council
For
Exposure
Policy
003.1
(Aug.
2000):
Agricultural
Transfer
Coefficients
This
document
provides
transfer
coefficients
which
have
been
used
to
assess
exposures
in
home
gardens.
114
°
Science
Advisory
Council
For
Exposure
Policy
12
(Feb.
2001):
Recommended
Revisions
To
The
Standard
Operating
Procedures
(SOPs)
For
Residential
Exposure
Assessment
This
document
provides
additional,
revised
guidance
for
completing
residential
exposure
assessments.
°
Overview
of
Issues
Related
To
The
Standard
Operating
Procedures
For
Residential
Exposure
Assessment
(August
1999
Presentation
To
The
FIFRA
SAP)
This
document
provides
rationale
for
Agency
changes
in
SOPs.
Companion
animal
approach
included
in
document
used
for
risk
assessment.
The
Agency
also
completed
a
specific,
screening
level
risk
assessment
for
Mud
and
Ghost
shrimp
control
in
Washington
State.
The
assessment
considering
swimming
in
areas
that
have
been
treated
as
well
as
oyster
harvesting
for
adults
and
playing
on
a
beach
for
toddlers.
The
calculations
for
these
scenarios
were
based
on
the
Agency's
SOPs
described
above,
the
Agency's
program,
and
data
generated
by
the
Washington
Department
of
Ecology.
The
specific
documents
that
were
consulted
include:
°
RAGS,
Part
A
Risk
Assessment
Guidance
For
Superfund,
Volume
1:
Human
Health
Evaluation
Manual
(Part
A),
Interim
Final
(EPA/
540/
1
89/
002,
December
1989)
This
document
was
consulted
for
overall
guidance
on
how
to
address
risks
from
exposure
to
contaminated
sediments.
°
RAGS,
Part
E
Risk
Assessment
Guidance
For
Superfund,
Volume
1:
Human
Health
Evaluation
Manual
(Part
E,
Supplemental
Guidelines
For
Dermal
Risk
Assessment),
Interim
Review
Draft
For
Public
Comment
(EPA/
540/
R/
99/
005,
September
2001)
This
document
was
consulted
for
overall
guidance
on
how
to
address
risks
from
exposure
to
contaminated
sediments.
Specific
soil
adherence
values
were
also
obtained
from
Exhibit
3
3,
page
3
18.
°
Carbaryl
Concentrations
In
Willapa
Bay
and
Recommendations
For
Water
Quality
Guidelines
(March
2001,
Pub
No.
01
03
005,
Author:
Art
Johnson)
Water
concentration
data
were
obtained
from
this
document.
It
presented
monitoring
data
collected
by
the
Washington
Department
of
Ecology
as
well
as
data
collected
by
the
Shoalwater
Bay
Tribe.
°
Screening
Survey
of
Carbaryl
(Sevin)
and
1
napthol
Concentrations
in
Willapa
Bay
Sediments
(May
1999,
Pub
No.
99
323,
Author:
Cynthia
Stonick)
Sediment
and
water
concentration
data
were
obtained
from
this
document.
115
When
the
guidance
in
current
labels
and
these
documents
is
considered,
it
is
clear
that
the
Agency
should
consider
children
of
differing
ages
as
well
as
adults
in
its
assessments.
It
is
also
clear
that
different
age
groups
should
be
considered
in
different
situations.
The
populations
that
were
considered
in
the
assessment
include:
C
Residential
(homeowner)
Adults:
these
individuals
are
members
of
the
general
population
that
are
exposed
to
chemicals
by
engaging
in
activities
at
their
residences
(e.
g.,
in
their
lawns
or
gardens)
and
also
in
areas
not
limited
to
their
residence
(e.
g.,
golf
courses
or
parks)
previously
treated
with
a
pesticide.
These
kinds
of
exposures
are
attributable
to
a
variety
of
activities
and
usually
addressed
by
the
Agency
in
risk
assessments
by
considering
a
representative
activity
as
the
basis
for
the
exposure
calculation.
C
Residential
Children:
children
are
members
of
the
general
population
that
can
also
be
exposed
in
their
residences
(e.
g.,
on
lawns,
in
gardens,
or
from
contact
with
treated
pets)
as
well
as
other
areas
previously
treated
with
a
pesticide
(e.
g.,
parks).
These
kinds
of
exposures
are
attributable
to
a
variety
of
activities
such
as
playing
outside,
home
gardening,
or
playing
with
a
companion
animal.
Toddlers
have
been
selected
as
a
sentinel
(or
representative)
population
for
turf
and
companion
animal
assessments.
Youth
aged
children
(ages
10
to
12)
are
considered
the
sentinel
population
for
a
fruit
harvesting
assessment
because
it
is
likely
that
children
of
this
age
would
help
with
garden
maintenance.
They
are
usually
addressed
by
the
Agency
in
risk
assessments
by
considering
a
representative
activities
for
each
age
group
in
an
exposure
calculation.
The
SOPs
For
Residential
Exposure
Assessment
define
several
scenarios
that
apply
to
uses
specified
in
current
labels.
These
scenarios
served
as
the
basis
for
the
residential
postapplication
assessment
along
with
the
modifications
to
them
and
the
additional
data/
approaches
described
above.
The
Agency
used
this
guidance
to
define
the
exposure
scenarios
that
essentially
include
child
exposure
on
treated
lawns
(dermal
and
nondietary
ingestion
considered),
child
exposure
in
treated
gardens,
exposure
to
children
from
treated
companion
animals,
and
the
exposure
of
adults
while
doing
gardening,
lawncare,
or
golfing.
The
SOPs
and
the
associated
scenarios
are
presented
below:
C
Dose
from
dermal
exposure
on
treated
turf
calculated
using
SOP
2.2:
Postapplication
dermal
dose
among
toddlers
from
playing
on
treated
turf;
C
Dose
from
ingestion
of
carbaryl
granules
from
treated
turf
calculated
using
SOP
2.3.1:
Postapplication
dose
among
toddlers
from
episodic
nondietary
ingestion
of
pesticide
granules
picked
up
from
treated
turf
(i.
e.,
those
residues
that
end
up
in
the
mouth
from
a
child
touching
turf
and
then
putting
their
hands
in
their
mouth);
116
C
Dose
from
hand
to
mouth
activity
from
treated
turf
calculated
using
SOP
2.3.2:
Postapplication
dose
among
toddlers
from
incidental
nondietary
ingestion
of
pesticide
residues
on
treated
turf
from
hand
to
mouth
transfer
(i.
e.,
those
residues
that
end
up
in
the
mouth
from
a
child
touching
turf
and
then
putting
their
hands
in
their
mouth);
C
Dose
from
object
to
mouth
activity
from
treated
turf
calculated
using
SOP
2.3.3:
Postapplication
dose
among
toddlers
from
incidental
nondietary
ingestion
of
pesticide
residues
on
treated
turf
from
object
to
mouth
transfer
(i.
e.,
those
residues
that
end
up
in
the
mouth
from
a
child
mouthing
a
handful
of
treated
turf);
C
Dose
from
soil
ingestion
activity
from
treated
turf
calculated
using
SOP
2.3.4:
Postapplication
dose
among
toddlers
from
incidental
nondietary
ingestion
of
pesticide
residues
from
ingesting
soil
in
a
treated
turf
area
(i.
e.,
those
soil
residues
that
end
up
in
the
mouth
from
a
child
touching
treated
soil
and
turf
then
putting
their
hands
in
their
mouth);
C
Dose
from
dermal
exposure
while
working
in
treated
gardens
or
with
various
trees
(nut,
fruit,
and
ornamentals)
calculated
using
SOPs
3.2
&
4.2:
Postapplication
dermal
dose
among
adults
and
youth
aged
children
(ages
10
to
12)
while
gardening
[Note:
These
series
of
SOPs
also
call
for
addressing
nondietary
ingestion,
these
types
of
exposures
have
been
included
in
the
turf/
toddler
calculations.
The
transfer
coefficients
used
are
from
updated
Agency.];
C
Postapplication
Potential
Dose
From
Incidental
Nondietary
Ingestion
if
Pesticide
Residues
While
Swimming
calculated
using
SOP
5.2.1:
Postapplication
potential
dose
among
adults
while
swimming
the
general
guidance
applies,
updates
to
this
SOP
have
been
completed
in
the
form
of
the
SWIMODEL
(V2.0)
which
was
used
for
this
assessment;
C
Dose
from
dermal
contact
with
treated
pets
calculated
using
SOP
9.2.1:
Postapplication
potential
dose
among
toddlers
from
the
dermal
contact
with
a
treated
pet
and
absorption
through
the
skin
(i.
e.,
residues
that
end
up
as
body
burden
after
deposition
on
and
absorption
through
the
skin);
and
C
Dose
from
hand
to
mouth
activity
calculated
using
SOP
9.2.2:
Postapplication
potential
dose
among
toddlers
from
nondietary
ingestion
of
pesticide
residues
on
treated
pets
from
hand
to
mouth
transfer
(i.
e.,
those
residues
that
end
up
in
the
mouth
from
a
child
touching
a
pet
and
then
putting
their
hands
in
their
mouth).
The
detailed
residential
postapplication
calculations
are
presented
in
Appendices
H
through
M
of
this
document.
Please
refer
to
them
to
review
the
specifics
of
the
risk
assessment.
Appendix
H
contains
the
turf
risk
assessment
for
adults
and
children.
Appendix
I
contains
the
risk
assessment
for
uses
in
gardens
and
fruit
trees
that
addresses
such
activities
as
harvesting
for
adults
and
youthaged
children.
Appendix
J
presents
the
risks
associated
with
uses
on
pets.
Appendix
K
provides
the
background
information
on
how
deposition
patterns
for
wide
area
applications
such
as
mosquito
adulticides
were
calculated.
Appendix
L
presents
the
risks
that
result
from
the
use
of
carbaryl
as
a
mosquito
adulticide.
This
assessment
is
essentially
the
same
as
that
done
for
turf
with
the
addition
117
of
a
factor
to
account
for
the
limited
amount
of
residues
that
are
deposited
on
turf
because
of
how
mosquito
adulticides
are
applied.
Appendix
M
presents
the
data
and
risk
calculations
used
to
address
carbaryl
use
for
Ghost
and
Mud
Shrimp
control
in
Washington
State.
3.2.2
Data
and
Assumptions
for
Residential
Postapplication
Exposure
Scenarios
A
series
of
assumptions
and
exposure
factors
served
as
the
basis
for
completing
the
residential
postapplication
risk
assessments.
Each
assumption
and
factor
are
detailed
below.
In
addition
to
these
values,
a
study
was
also
submitted
by
the
Aventis
Corporation
which
was
not
used
by
the
Agency
in
this
assessment.
The
study,
however,
is
identified
below
for
recordkeeping
purposes
along
with
the
rationale
for
not
using
it
in
the
assessment.
The
assumptions
and
factors
used
in
the
risk
calculations
are
consistent
with
current
Agency
policy
for
completing
residential
exposure
assessments
(i.
e.,
SOPs
For
Residential
Exposure
Assessment).
[Note:
More
detail
about
the
origin
of
each
factor
can
be
obtained
in
the
SOP
document
and
associated
documents
such
as
the
Agency's
1999
Overview
document
presented
to
the
FIFRA
SAP.]
The
values
used
in
this
assessment
include:
C
There
are
many
factors
that
are
common
to
the
occupational
and
residential
postapplication
risk
assessments
such
as
body
weights
for
adults,
analysis
of
residue
dissipation
data,
and
transfer
coefficients
used
for
the
garden
exposure
scenarios.
Please
refer
to
the
assumptions
and
factors
in
Section
2.1.2
for
further
information
concerning
these
common
values.
[Note:
The
transfer
coefficients
have
not
been
adjusted
for
the
clothing
that
someone
working
in
their
home
garden
might
be
anticipated
to
wear
such
as
shorts
and
short
sleeved
shirt.]
°
Carbaryl
labels
allow
for
wide
area
applications
in
mosquito
control
(for
adulticides)
and
for
the
control
of
other
pest
species
such
as
black
fly.
When
the
Agency
considers
these
use
patterns
in
risk
assessments,
the
amount
deposited
on
the
turf
is
determined
by
the
using
the
AgDrift
model
for
aerial
applications
(9.5
percent
deposits
on
turf)
and
published
data
from
the
scientific
literature
for
ground
fogger
applications
(5
percent
deposits
on
turf)
as
described
in
Appendix
K.
All
other
components
are
similar
to
a
residential
turf
risk
assessment.
The
Sevin
XLR
label
for
mosquito
and
fly
control
was
key
in
defining
the
input
parameters
for
the
AgDrift
calculations.
This
label
specified
a
range
of
application
rates
from
0.016
to
1
lb
ai/
acre.
The
label
also
indicated
that
the
optimal
droplet
size
range
is
from
8
to
30
µm.
However,
the
label
also
had
specific
requirements
for
aerial
applications
for
droplets
"with
a
calculated
VMD
of
less
than
50
µm"
and
an
allowance
that
"no
more
than
5
percent
of
the
droplets
should
be
larger
than
80
µm."
Once
the
deposition
patterns
have
been
defined,
a
turf
type
risk
assessment
was
completed
accounting
for
different
deposition
patterns,
compared
to
a
typical
turf
risk
assessment.
Different
deposition
patterns
were
accounted
for
in
the
calculation
of
the
turf
transferable
residues
to
which
adults
and
children
are
exposed.
The
calculations
are
presented
in
Appendix
L.
°
Exposure
frequency
values
used
in
cancer
risk
assessments
for
adults
are
the
same
as
those
used
for
residential
handlers
(1
time
per
year).
However,
the
Agency
does
believe
that
there
118
are
higher
frequency
golfers
(i.
e.,
average
golfers
over
all
ages
play
18
rounds
year)
based
on
a
1992
report
(Golf
Course
Operations,
Cost
of
Doing
Business/
Profitability
by
the
Center
For
Golf
Course
Management).
The
Agency
also
believes
that
individuals
may
reenter
treated
home
gardens
more
than
one
time
per
year.
However,
exact
information
linking
the
timing
of
applications
and
the
frequency
of
reentry
is
not
available.
It
should
be
noted
that
this
issue
is
being
addressed
by
the
Agency
in
the
development
of
calendar
based,
residential
modeling
programs
such
as
Lifeline.
Therefore,
until
calendar
based
approaches
are
implemented,
only
single
reentry
events
have
been
considered
in
the
cancer
risk
assessment.
Risk
managers
should
consider
the
likelihood
of
additional
reentry
events
when
interpreting
the
results
of
the
cancer
risk
assessment.
To
refine
these
results,
the
Agency
has
also
calculated
the
number
of
exposure
days
allowed
per
year
to
achieve
a
1x10
6
cancer
risk
ceiling
just
as
with
the
residential
handler
assessment
above.
Risk
managers
should
also
consider
the
likelihood
of
intermediate
term
exposures
occurring
for
adults.
The
Agency
calculated
intermediate
term
postapplication
risks
for
adults
yet,
in
reality,
the
population
where
these
exposures
would
be
expected
is
likely
very
small
except
for
maybe
home
gardeners.
The
Agency
also
calculated
intermediate
term
exposures
for
youth
aged
children
and
toddlers
where
the
behaviors
used
as
the
basis
for
the
risk
assessment
are
thought
to
more
likely
occur
on
a
routine
basis
(i.
e.,
the
population
would
be
expected
to
be
larger).
°
The
Agency
combines
or
aggregates
risks
resulting
from
exposures
to
individual
chemicals
when
it
is
likely
they
can
occur
simultaneously
based
on
the
use
pattern
and
the
behavior
associated
with
the
exposed
population.
Within
a
residential
assessment,
this
can
take
two
forms.
The
first
is
to
add
together
risks
for
individual
exposure
scenarios
from
all
likely
sources
of
exposure
such
as
after
an
application
to
turf
or
use
on
a
pet.
For
carbaryl,
the
Agency
has
added
together
risk
values
(i.
e.,
MOEs)
for
different
kinds
of
exposures
within
the
turf
(dermal,
hand
to
mouth,
object
to
mouth,
and
soil
ingestion)
and
pet
scenarios
(dermal
and
hand
to
mouth).
These
represent
the
standard
set
of
exposures
that
are
typically
added
together
when
chemicals
are
used
on
turf
or
on
pets
because
it
is
logical
they
can
co
occur.
The
second
is
to
add
exposures
from
different
residential
exposure
scenarios
that
can
possibly
co
occur
such
as
when
a
homeowner
makes
an
application
and
then
checks
their
garden
for
bugs
a
few
hours
later
on
the
same
day.
Typically,
the
Agency
only
adds
exposures
from
different
exposure
scenarios
together
(e.
g.,
spraying
and
gardening)
when
risks
from
both
are
not
already
a
concern.
For
carbaryl,
however,
there
are
risk
concerns
for
many
residential
handler
scenarios
so
the
Agency
did
not
add
risk
values
from
any
postapplication
exposure
together
with
applicator
risks.
119
°
The
frequency
of
retreatment
could
not
be
determined
based
on
information
provided
by
the
Aventis
Corporation
at
the
SMART
meeting
or
other
associated
information.
Labels
generally
specify
a
minimum
interval
of
1
week
between
applications.
The
risk
assessments
are
based
on
five
different
residue
(DFR
or
TTR)
studies.
In
all
studies
except
on
olives,
multiple
applications
were
completed
at
1
week
intervals
so
any
additivity
between
applications
would
also
be
accounted
for
in
the
empirical
data
used
for
risk
assessment.
C
Exposures
to
children
playing
on
treated
turf
as
well
as
adults
on
turf
(lawncare
and
golfing)
have
been
addressed
using
the
latest
Agency
approaches
for
this
scenario
including:
°
5
percent
of
the
application
rate
has
been
used
to
calculate
the
0
day
residue
levels
used
for
defining
risks
from
hand
to
mouth
behaviors,
measured
TTR
values
are
not
used
because
of
differences
in
transferability
versus
what
would
be
expected
during
hand
to
mouth
behaviors;
°
20
percent
of
the
application
rate
has
been
used
to
calculate
the
0
day
residue
levels
used
for
defining
risks
from
object
to
mouth
behaviors,
measured
TTR
values
are
not
used
because
of
differences
in
transferability
versus
what
would
be
expected
during
hand
to
mouth
behaviors,
a
higher
percent
transfer
has
been
used
for
objectto
mouth
behaviors
because
it
involves
a
teething
action
believed
to
be
more
analogous
to
DFR/
leaf
wash
sample
collection
where
20
percent
is
also
used;
°
the
measured
TTR
levels
quantified
in
MRID
451143
01
have
been
used
to
complete
the
dermal
exposure
calculations
as
the
0
day
transferability
was
>
1
percent
of
the
application
rate
for
the
short
and
intermediate
term
data
sources,
studies
where
transferability
is
less
than
1
percent
are
not
used
for
risk
assessment
purposes
because
the
transfer
coefficients
used
by
the
Agency
for
defining
exposures
are
based
on
Jazzercize
studies
in
which
TTR
values
were
measured
by
techniques
where
transferability
is
generally
in
the
1
to
5
percent
range
other
than
the
ORETF
roller
method
where
transferability
tends
to
be
lower;
°
short
and
intermediate
term
exposures
have
been
calculated
because
play
and
mouthing
behaviors
are
assumed
to
routinely
occur
daily
and
for
extended
periods
such
as
over
30
days,
carbaryl
residues
are
also
expected
to
be
present
based
on
residue
dissipation
data
(i.
e.,
slow
dissipation
rate);
°
in
cases
where
0
day
residues
have
been
calculated
based
on
application
rates
(i.
e.,
hand/
object
to
mouth
residues
and
for
soil
dissipation),
dissipation
over
time
measured
in
the
TTR
study
(i.
e.,
slope
of
decay
curve)
has
been
used
to
predict
TTR
and
soil
levels
over
time,
carbaryl
residues
were
detectable
even
at
14
days
after
application
(i.
e.,
final
sampling
interval)
at
all
sites
in
the
TTR
studies
used
in
this
assessment,
at
14
days
average
residues
at
the
Georgia
and
Pennsylvania
study
sites
were
still
orders
of
magnitude
above
the
quantitation
limit,
this
indicates
that
predicted
residue
levels
for
extended
durations
should
be
considered
appropriate
based
on
the
empirical
data
(e.
g.,
critical
for
consideration
of
intermediate
term
exposures);
120
°
the
transfer
coefficients
used,
except
golfing,
are
those
presented
at
the
1999
Agency
presentation
before
the
FIFRA
Science
Advisory
Panel
that
have
been
adopted
in
routine
practice
by
the
Agency;
°
transfer
coefficients
have
been
adjusted
for
differences
between
short
and
intermediate
term
exposures;
°
adult
golfers
have
been
assessed
using
a
transfer
coefficient
of
500
cm
2
/hour
[Note:
The
Agency
is
currently
developing
a
policy
on
golfer
exposures
and
has
used
this
value
in
other
assessments];
°
3
year
old
toddlers
are
expected
to
weigh
15
kg;
°
hand
to
mouth
exposures
are
based
on
a
frequency
of
20
events/
hour
and
a
surface
area
per
event
of
20
cm
2
representing
the
palmar
surfaces
of
three
fingers;
°
saliva
extraction
efficiency
is
50
percent
meaning
that
every
time
the
hand
goes
in
the
mouth
approximately
½
of
the
residues
on
the
hand
are
removed;
°
object
to
mouth
exposures
are
based
on
a
25
cm
2
surface
area;
°
exposure
durations
are
expected
to
be
2
hours
based
on
information
in
the
Agency's
Exposure
Factors
Handbook
except
for
golfers
where
the
exposure
duration
for
an
18
hole
round
of
golf
is
4
hours
based
on
a
1992
report
(Golf
Course
Operations,
Cost
of
Doing
Business/
Profitability
by
the
Center
For
Golf
Course
Management);
°
soil
residues
are
contained
in
the
top
centimeter
and
soil
density
is
0.67
mL/
gram;
°
dermal,
hand
and
object
to
mouth,
and
soil
ingestion
are
added
together
to
represent
an
overall
risk
from
exposure
to
turf
while
granular
ingestion
is
considered
to
be
a
much
more
episodic
behavior
and
is
considered
separately
by
the
Agency;
and
°
children
of
various
ages
down
to
the
very
young
(e.
g.,
4
or
5
years
old)
are
currently
playing
golf,
the
Agency
recognizes
that
age
may
impact
exposures
because
of
changes
in
behavior
and
skin
surface
area
to
body
weight
ratios
but
has
not
yet
developed
a
quantitative
approach
for
calculating
their
risks.
C
Exposures
to
children
and
adults
working
in
home
gardens
have
been
addressed
using
the
latest
Agency
approaches
for
this
scenario
including:
°
youth
aged
children
are
considered
along
with
adults;
°
12
year
old
youth
are
expected
to
weigh
39.1
kg;
°
exposure
durations
are
expected
to
be
40
minutes;
°
Pre
Harvest
Intervals
(PHIs)
are
less
than
7
days
for
most
crops
with
some
as
long
as
28
days;
°
transfer
coefficients
for
youth
were
calculated
by
adjusting
the
appropriate
adult
transfer
coefficients
by
a
50%
factor
as
has
been
done
by
the
Agency
since
the
inception
of
the
SOPs
For
Residential
Exposure
Assessment;
°
the
updated
transfer
coefficients
specified
in
Agency
policy
003
described
above
in
the
occupational
risk
assessment
have
been
used
rather
than
those
currently
specified
in
the
SOPs
because
they
represent
more
refined
estimates
of
exposure
for
the
fruiting
vegetable
and
deciduous
tree
crop
groups,
these
crop
groups
have
been
used
in
the
SOPs
to
represent
home
garden
exposures;
121
°
the
combination
of
adjusting
transfer
coefficients
for
youth
aged
children
and
using
appropriate
body
weights
for
the
age
group
results
in
dose
levels
that
are
slightly
lower
than
that
of
adults
in
the
same
activity
(the
TC
reduction
and
body
weight
reduction
is
essentially
a
1:
1
ratio);
and
°
the
DFR
data
used
for
the
assessments
are
the
same
as
those
used
in
the
occupational
risk
assessment
for
the
selected
crop
groups.
C
Exposures
to
children
after
contact
with
treated
pets
have
been
addressed
using
the
latest
Agency
approaches
for
this
scenario
including:
°
only
toddlers
are
considered
because
their
exposures
are
thought
to
be
highest
(i.
e.,
they
are
considered
the
sentinel
population
by
the
Agency);
°
a
equilibrium
approach
based
on
a
single
child
"hug"
of
the
treated
animal
is
used
to
assess
dermal
exposure
as
described
in
the
1999
Agency
SAP
Overview
document
(i.
e.,
the
skin
loads
after
a
single
contact
with
the
treated
animal
and
additional
contacts
don't
proportionally
add
exposures),
the
surface
area
of
the
dermal
hug
is
based
on
a
toddler
skin
surface
area
and
typical
clothing;
°
residue
dissipation
is
5
percent
per
day
for
the
shampoo
and
dust
products
(based
on
data
from
J.
Chambers
at
Mississippi
State
University
on
other
pet
use
products);
°
the
transferability
of
residues
from
fur
is
20
percent;
°
the
active
lifetime
of
a
collar
is
expected
to
be
120
days
based
on
label
statements
which
was
used
by
the
Agency,
a
daily
emission
term
from
the
collar
of
0.000290
mg/
cm
2
/gram
ai/
day
is
also
based
on
measured
data
from
Mississippi
State
University
for
a
pet
collar;
°
risks
are
based
on
an
even
loading
of
residues
across
the
entire
surface
of
a
30
lb
dog
which
has
been
chosen
as
a
representative
animal,
the
animal
surface
area
was
calculated
using
(12.3
*
Body
Weight
(g)
0.65
)
from
the
Agency's
1993
Wildlife
Exposure
Factors
Handbook
(i.
e.,
dog
surface
area
of
5986
cm
2
);
°
the
daily
frequency
of
hand
to
mouth
contact
with
dogs
is
40
events
per
day,
in
each
event,
the
palmar
surface
of
the
hands
(i.
e.,
20cm
2
/event)
is
placed
in
the
mouth
of
the
child
contributing
to
nondietary
ingestion
exposure;
and
°
the
Agency
is
currently
in
the
process
of
considering
revisions
in
its
methodologies
for
completing
risk
assessments
for
pet
products,
some
of
the
key
inputs
that
are
potentially
subject
to
modification
include
the
amount
of
residues
which
are
transferable
from
pet
fur,
defining
the
number
of
hand
to
mouth
events,
and
evaluating
the
emission
term
for
collars.
°
For
turf,
the
maximum
application
rate
indicated
at
the
SMART
meeting
was
8
lb
ai/
acre
even
though
current
labels
allow
for
applications
by
homeowners
at
up
to
11
lb
ai/
acre
for
Lock
n
load
type
packages
and
9
lb
ai/
acre
for
granulars.
The
TTR
study
was
conducted
also,
it
should
be
noted,
at
8
lb
ai/
acre
(see
below
for
more
details).
Based
on
the
design
of
the
TTR
study
and
what
was
indicated
at
the
SMART
meeting,
the
Agency
completed
the
postapplication
assessment
using
the
data
directly
from
the
TTR
study
without
any
adjustment
for
application
rate.
Risks
at
higher
application
rates
would
be
worse
than
those
presented
at
the
8
lb
ai/
A
application
rate
(see
below).
°
For
pet
uses,
the
Agency
is
considering
modifications
in
its
pet
risk
assessment
methods.
122
These
revisions
are
based
on
the
availability
and
interpretation
of
data
from
academic
researchers
and
the
pesticide
industry.
These
data
will
be
used
to
refine
and
better
characterize
risks
associated
with
uses
on
pets
as
they
become
available.
C
Postapplication
residential
risks
are
based
generally
on
maximum
application
rates
or
values
specified
in
the
SOPs
For
Residential
Exposure
Assessment.
C
The
Jazzercise
approach
is
the
basis
for
the
dermal
transfer
coefficients
as
described
in
the
Agency's
Series
875
guidelines,
SOPs
For
Residential
Exposure
Assessment,
and
the
1999
FIFRA
SAP
Overview
document
C
There
are
many
likely
studies
focused
on
carbaryl
in
the
published
literature
or
available
from
various
governmental
Agencies
because
it
is
so
widely
used.
For
example,
the
Agency's
Office
of
Research
and
Development
along
with
other
Agencies
have
funded
a
project
entitled
Pesticide
Exposure
in
Children
Living
in
Agricultural
Areas
along
the
United
States
Mexico
Border
Yuma
County,
Arizona.
Preliminary
results
of
this
study
indicate
that
carbaryl
residues
were
identified
in
the
dust
of
20
percent
of
the
152
houses
sampled
and
in
approximately
24
percent
in
25
samples
collected
in
6
schools
in
the
same
region.
At
this
point,
the
Agency
has
not
identified
any
data
from
the
literature
or
other
sources
that
would
alter
the
conclusions
of
this
risk
assessment.
As
more
data
become
available,
the
Agency
will
consider
the
information
in
efforts
to
refine
the
assessment
(i.
e.,
use
additional
information
to
alter
numeric
risk
estimates
or
to
characterize
existing
estimates
if
warranted).
With
regard
to
this
specific
example,
current
Agency
policy
is
not
to
use
house
dust
estimates
to
calculate
risks
because
of
a
lack
of
an
appropriate
exposure
model.
Also,
in
a
1995
study
conducted
by
the
Centers
For
Disease
Control
(Hill
et
al)
entitled
Pesticide
Residues
In
Urine
Of
Adults
Living
In
The
United
States:
Reference
Range
Concentrations,
1000
adults
were
monitored
via
urine
collection.
One
of
the
analytes
measured
in
that
study
(1
napthol)
is
a
potential
metabolite
of
carbaryl
as
well
as
of
napthalene
and
napropamide.
This
metabolite
was
identified
in
86
percent
of
the
1000
adults
monitored
where
the
mean
value
was
17
ppb
and
the
99
th
percentile
was
290
ppb.
These
values
were
not
used
quantitatively
in
the
risk
assessment
for
carbaryl
because
of
the
uncertainties
associated
with
them
such
as
the
exact
contribution
of
each
possible
compound
to
the
overall
levels
and
no
linked
exposure
information.
The
investigators
also
reported
results
for
(2
napthol)
which
is
also
a
metabolite
of
napthalene
and
indicated
a
common
source
of
exposure
because
1
napthol
and
2
napthol
levels
were
similar
based
on
a
Pearson
correlation
of
0.64
(P=
0.0001).
The
mean
for
2
napthol
is
7.2
ppb
and
the
99
th
percentile
was
54
ppb.
These
levels
were
The
Agency
instead
considers
them
a
qualitative
indicator
that
exposures
in
the
general
population
are
likely
to
occur.
C
The
Aventis
Corporation
is
in
the
process
of
conducting
a
biomonitoring
study
with
children
who
live
in
households
where
carbaryl
has
been
used.
Preliminary
results
indicate
that
levels
at
the
highest
percentiles
of
the
distribution
are
similar
to
those
predicted
in
the
Agency's
turf
risk
assessments
for
toddlers
which
are
intended
to
represent
the
higher
percentiles
of
the
exposure
distribution.
A
more
detailed
analysis
will
be
completed
upon
submission.
Aventis
is
also
a
member
of
the
Residential
Exposure
Joint
Venture
where
the
123
objective
is
to
collect
use
data
for
consumer
products
containing
pesticides.
These
data
will
also
be
considered
if
submitted
to
the
Agency.
C
In
Washington
state,
carbaryl
is
used
under
a
24C
label
(WA
900013)
to
control
Ghost
and
Mud
shrimp
in
Willapa
Bay.
The
Agency
considered
contact
with
sediments
(e.
g.,
oyster
digging
for
adults
and
playing
on
beach
for
toddlers)
and
water
(adult
swimming)
that
could
contain
carbaryl
residues
using
commonly
accepted
risk
assessment
methods
(i.
e.,
RAGS
Superfund
Guidance
and
SWIMODEL
(V2.0)),
water
monitoring
data,
and
sediment
data.
In
these
assessments,
conservative
inputs
for
sediment
and
water
concentrations
were
used
and
also
conservative
exposure
factors
were
used
to
ensure
the
screening
level
nature
of
the
calculations.
Such
inputs
included
selection
of
the
highest
water
concentration
estimate
from
all
available
data
sources
for
swimmers
and
highest
sediment
concentrations
for
oyster
digging
or
children
playing.
Other
conservative
inputs
included
the
permeation
coefficient
from
the
SWIMODEL,
the
use
of
a
90
th
percentile
value
for
the
duration
of
swimming
for
a
noncompetitive
swimmer
of
3
hours
(which
would
be
expected
to
be
conservative
in
the
areas
where
this
use
occurs),
and
the
entire
surface
area
of
a
toddler
used
for
playing
on
a
beach.
[Note:
The
water
and
sediment
concentration
data
have
been
reviewed
by
the
Agency's
Environmental
Fate
and
Effects
Division
(D279109,
Thomas
Steeger
author).]
Postapplication
Study:
One
study,
conducted
by
the
Aventis
Corporation,
which
measured
concurrent
dermal
exposure
using
Jazzercize
and
turf
transferable
residues
of
Ronstar
50WP
(oxadiazon)
was
submitted
for
use
in
the
risk
assessment.
The
use
of
this
study
was
not
accepted
because
it
is
very
specific
to
the
use
of
oxadiazon
on
turf.
In
particular,
the
study
was
conducted
on
a
dormant
grass
and
the
transfer
coefficients
differ
from
those
currently
used
in
standard
Agency
risk
assessments.
In
fact,
the
ORETF,
of
which
Aventis
is
a
member,
considered
this
study
for
purchase
and
use
in
its
generic
approach
to
dermal
exposures
on
turf.
Based
on
essentially
the
same
reasons
as
the
Agency
has
used,
the
study
was
not
purchased.
For
clarification
purposes,
the
following
information
can
be
used
to
identify
the
study:
C
Evaluation
of
Turf
Reentry
Exposure
To
a
Broadcast
Application
of
Ronstar
50WP
EPA
MRID
447425
01;
Report
dated
January
18,
1995;
Authors:
Leah
Rosenheck
and
Shirley
Sanchez;
Sponsor:
Aventis
Corporation
(formerly
Rhone
Poulenc).
3.2.3
Residential
Postapplication
Exposure
and
Noncancer
Risk
Estimates
The
residential
postapplication
exposure
and
non
cancer
risk
calculations
are
presented
in
this
section.
Noncancer
risks
were
calculated
using
the
Margin
of
Exposure
(MOE)
which
is
a
ratio
of
the
body
burden
to
the
toxicological
endpoint
of
concern.
Exposures
were
calculated
by
considering
the
potential
sources
of
exposure
(i.
e.,
DFRs
on
garden
plants,
TTRs
on
lawns,
and
transferable
residues
on
treated
pets)
then
calculating
dermal
and
nondietary
ingestion
exposures.
The
major
difference
with
residential
risk
assessments
is
that
the
uncertainty
factor
which
defines
the
level
of
risk
concern
also
has
to
consider
application
of
the
additional
FQPA
safety
factor
specified
by
the
legislation.
In
the
case
of
carbaryl,
in
January
and
February
2002
meetings
of
the
FQPA
Safety
Factor
Committee,
it
was
decided
that
the
FQPA
factor
should
be
reduced
to
1.
Therefore,
the
overall
uncertainty
factor
applied
to
carbaryl
for
residential
postapplication
risk
124
assessments
is
100
which
is
based
on
the
FQPA
safety
factor
of
1
along
with
the
100
applied
for
inter
species
extrapolation,
intra
species
sensitivity,
and
the
use
of
a
NOAEL
for
risk
assessment.
Dermal
exposures
and
risks
from
lawn
and
garden
uses
were
calculated
in
the
same
manner
as
described
above
in
Section
2.2.3.
Dermal
exposures
from
treated
pets
were
calculated
using
a
slightly
different
approach
where
a
"hug"
contact
is
expected
to
lead
to
an
equilibrium
concentration
on
the
skin
of
the
affected
individual.
Exposures
to
sediment
and
water
while
swimming
were
calculated
using
a
soil
adherence
approach
analogous
to
that
used
in
Superfund
risk
assessments
and
swimmer
exposures
were
calculated
using
the
SWIMODEL
which
has
been
validated
and
also
brought
before
the
FIFRA
SAP.
Along
with
calculating
these
dermal
exposures,
other
aspects
of
the
turf,
treated
pet,
and
sediment
exposure
scenarios
involved
calculating
dose
from
non
dietary
ingestion.
The
algorithms
used
for
each
type
of
calculation
are
presented
below
which
have
not
been
previously
addressed
in
Section
2.2.3.
Nondietary
Ingestion
Exposure
From
Treated
Turf:
Nondietary
ingestion
exposure
levels
from
turf
were
calculated
using
the
following
equations.
These
values
were
then
used
to
calculate
MOEs
as
illustrated
above.
The
following
illustrates
the
approach
used
to
calculate
the
nondietary
ingestion
exposures
that
are
attributable
to
hand
to
mouth
behavior
on
treated
turf
(SOP
2.3.2):
where:
D
=
dose
from
hand
to
mouth
activity
(mg/
day);
TTR
=
Turf
Transferable
Residue
where
dissipation
is
based
on
TTR
study
and
the
0
day
value
is
based
on
the
5%
initial
transferability
factor
(µg/
cm
2
);
SE
=
saliva
extraction
factor
(%);
SA
=
surface
area
of
the
hands
(cm
2
);
Freq
=
frequency
of
hand
to
mouth
events
(events/
hour);
and
Hr
=
exposure
duration
(hours).
The
following
illustrates
the
approach
used
to
calculate
exposures
that
are
attributable
to
object
to
mouth
behavior
on
treated
turf
that
is
represented
by
a
child
mouthing
on
a
handful
of
turf
(SOP
2.3.3):
where:
D
=
dose
from
mouthing
activity
(mg/
day);
TTR
=
Turf
Transferable
Residue
where
dissipation
is
based
on
TTR
study
and
the
0
day
value
is
based
on
the
20%
initial
transferability
factor
(µg/
cm
2
);
and
IgR
=
ingestion
rate
for
mouthing
of
grass
per
day
(cm
2
/day).
The
following
illustrates
the
basics
of
the
approach,
used
to
calculate
exposures
that
are
attributable
to
soil
ingestion
(SOP
2.3.4):
125
where:
D
=
dose
from
soil
ingestion
activity
(mg/
day);
SR
=
Soil
Residue
where
dissipation
is
based
on
TTR
study
and
the
0
day
value
is
based
on
the
application
rate,
1
cm
depth
of
surface
soil,
and
the
density
of
soil
(µg/
cm
3
);
and
IgR
=
ingestion
rate
for
daily
soil
ingestion
(mg/
day).
Dermal
Exposure
From
Treated
Pets:
Dermal
exposure
from
treated
pets
was
calculated
using
the
following
equation.
These
values
were
then
used
to
calculate
MOEs
as
illustrated
above.
This
approach
is
based
on
the
Agency
presentation
at
the
1999
FIFRA
Science
Advisory
Panel
and
is
detailed
in
the
accompanying
overview
document.
where:
D
=
dose
from
dermal
pet
contact
(mg/
day);
AR
=
application
rate
or
amount
applied
to
animal
in
a
single
treatment
(mg
ai/
animal);
FAR
=
fraction
of
the
application
rate
available
for
dermal
contact
as
transferable
residue
(%/
100);
SApet
=
surface
area
of
a
treated
dog
(cm
2
/animal);
t
=
time
after
application
(days);
DR
=
fractional
dissipation
rate
per
day
(%
per
day/
100);
and
SA
hug
=
surface
area
of
a
child
hug
(cm
2
contact/
hug).
[Note:
For
collars,
the
((
AR/
FAR)/
SApet)
term
is
replaced
with
a
measured
emission
term
of
0.00029
mg/
cm
2
/gram
ai
in
collar/
day
which
is
then
multiplied
by
the
amount
of
active
ingredient
in
the
collar
to
calculate
risks.]
Nondietary
Exposure
From
Treated
Pets:
Nondietary
exposure
from
treated
pets
was
calculated
using
the
following
equation
(SOP
9.2.2).
This
exposure
pathway
occurs
when
children
touch
animals
then
put
their
hands
in
their
mouths.
These
values
were
then
used
to
calculate
MOEs
as
illustrated
above.
126
where:
D
=
nondietary
ingestion
dose
from
with
treated
pets
(mg/
day);
AR
=
application
rate
or
amount
applied
to
animal
in
a
single
treatment
(mg
ai/
animal);
FAR
=
fraction
of
the
application
rate
available
for
dermal
contact
as
transferable
residue
(%/
100);
SApet
=
surface
area
of
a
treated
dog
(cm
2
/animal);
t
=
time
after
application
(days);
DR
=
fractional
dissipation
rate
per
day
(%
per
day/
100);
SAL
=
saliva
extraction
factor
(%
extractability);
SAhands
=
surface
area
of
the
hands
(cm
2
);
Freq
=
frequency
of
hand
to
mouth
events
(events/
day).
[Note:
Collar
emissions
are
defined
as
described
above
for
dermal
exposures.]
Mosquito
Control
Applications:
Mosquito
control
and
other
uses
(e.
g.,
black
fly
treatments)
have
been
addressed
using
a
methodology
that
involves
defining
how
much
material
is
deposited
on
the
ground
in
impacted
areas
then
using
the
same
methodology
that
is
used
for
a
turf
risk
assessment.
The
calculations
for
defining
how
much
deposited
on
the
ground
after
such
applications
involved
published
literature
for
ground
based
techniques
and
the
AgDrift
model
for
aerial
application
methods
(see
Appendix
K
for
further
information).
See
above
for
turf
risk
assessment
calculations.
Ghost
and
Mud
Shrimp
24C
Applications:
Applications
to
Willapa
Bay
in
Washington
state
have
been
addressed
using
the
SWIMODEL
and
guidance
from
RAGS.
The
SWIMODEL
provides
exposure
rates
(mg/
day)
from
several
routes
of
exposure.
Dermal
exposures
were
separated
out
to
apply
the
NOAEL
from
the
21
day
dermal
rat
study
(i.
e.,
20
mg/
kg/
day)
using
a
simple
proportion.
All
other
calculations
were
similar
to
other
scenarios
for
MOEs
and
dose.
Sediment
exposures
included
a
dermal
component
for
adults
and
toddlers
and
a
hand
tomouth
component
for
toddlers.
Dermal
exposures
to
sediments
were
calculated
using
the
following:
where:
D
=
potential
dose
from
dermal
sediment
contact
(mg/
kg/
day);
Sed
=
concentration
of
carbaryl
in
sediment
(µg/
kg
or
ppb),
varies
over
time
with
concentration
data
obtained
from
WA
state
reports
and
linear
extrapolation
between
Day
2
and
Day
30
data;
Adh
=
soil
adherence
factor
(mg/
cm
2
);
SA
=
surface
area
of
the
body
parts
contacted
(cm
2
);
and
BW
=
body
weight
(kg).
127
Nondietary
ingestion
exposures
that
are
attributable
to
hand
to
mouth
behavior
for
toddlers
on
beaches
were
calculated
as
follows:
where:
D
=
dose
from
hand
to
mouth
activity
(mg/
kg/
day);
Sed
=
concentration
of
carbaryl
in
sediment
(µg/
kg
or
ppb),
varies
over
time
with
concentration
data
obtained
from
WA
state
reports
and
linear
extrapolation
between
Day
2
and
Day
30
data;
SE
=
saliva
extraction
factor
(%);
SA
=
surface
area
of
the
hands
(cm
2
);
Adh
=
soil
adherence
factor
(mg/
cm
2
);
and
BW
=
body
weight
(kg).
Noncancer
Risk
Summary:
All
of
the
noncancer
risk
calculations
for
the
various
residential
carbaryl
assessments
are
included
in
Appendices
H,
I,
J,
K,
L
and
M
for
the
turf,
home
garden,
pet,
mosquito
control
and
oyster
bed
scenarios,
respectively.
[Note:
Both
Appendices
K
and
L
pertain
to
mosquito
control.]
The
specifics
of
each
of
table
included
in
these
Appendices
are
described
below.
A
summary
of
the
results
for
each
scenario
considered
for
each
timeframe
is
also
provided
below.
C
Appendix
H/
Table
1
:
Carbaryl
Postapplication
Residential
Turf
Risk
Assessment
Inputs
Contains
each
numerical
input
utilized
in
the
calculation
of
the
residential
postapplication
risk
values.
C
Appendix
H/
Table
2
:
Residue
Levels
Used
For
Carbaryl
Residential
Risk
Assessment
On
Turf
Presents
the
turf
transferable
residue
values
used
for
the
dermal,
hand
to
mouth,
object
to
mouth,
and
soil
ingestion
risk
assessments.
Includes
daily
values
which
have
been
used
for
short
term
exposures
and
30
day
average
values
which
have
been
used
for
intermediate
term
exposures.
C
Appendix
H/
Table
3:
Adult
Noncancer
Risk
Values
For
Carbaryl
Residential
Risk
Assessment
on
Turf
Presents
the
risks
for
short
term
and
intermediate
term
adult
dermal
exposures
in
on
turf
while
engaged
in
high
contact
activity
such
as
heavy
lawncare
("
On
Residential
Turf")
or
while
playing
golf
on
a
treated
course.
C
Appendix
H/
Table
5:
Toddler
Dermal
Risk
Values
For
Carbaryl
on
Turf
Presents
the
risks
for
short
term
and
intermediate
term
toddler
dermal
exposures
in
on
turf
while
engaged
in
high
contact
activity.
C
Appendix
H/
Table
6:
Toddler
Hand
to
Mouth
Risk
Values
For
Carbaryl
on
Turf
Presents
the
risks
for
short
term
and
intermediate
term
toddler
hand
to
mouth
exposures
in
on
turf
while
engaged
in
high
contact
activity.
C
Appendix
H/
Table
7:
Toddler
Object
to
Mouth
Risk
Values
For
Carbaryl
on
Turf
128
Presents
the
risks
for
short
term
and
intermediate
term
toddler
object
to
mouth
exposures
in
on
turf
while
engaged
in
high
contact
activity.
°
Appendix
H/
Table
8:
Toddler
Soil
Ingestion
Risk
Values
For
Carbaryl
on
Turf
Presents
the
risks
for
short
term
and
intermediate
term
toddler
soil
ingestion
exposures
in
on
turf
while
engaged
in
high
contact
activity.
°
Appendix
H/
Table
9:
Toddler
Aggregate
Risk
Values
For
Carbaryl
on
Turf
Presents
the
risks
for
short
term
and
intermediate
term
toddler
aggregate
exposures
in
on
turf
while
engaged
in
high
contact
activity.
C
Appendix
I/
Table
1:
Carbaryl
Postapplication
Residential
Garden
and
Tree
Use
Risk
Assessment
Inputs
Presents
the
numerical
unit
exposure
values
and
other
factors
used
in
the
tree
and
garden
postapplication
risk
assessments.
C
Appendix
I/
Table
2:
Carbaryl
Residential
Postapplication
Adult
Risk
Assessment
For
Deciduous
Tree
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
I/
Table
4:
Carbaryl
Residential
Postapplication
Youth
Risk
Assessment
For
Deciduous
Tree
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
I/
Table
5:
Carbaryl
Residential
Postapplication
Adult
Risk
Assessment
For
Fruiting
vegetable
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
I/
Table
7:
Carbaryl
Residential
Postapplication
Youth
Risk
Assessment
For
Fruiting
vegetable
Crop
Group
Risk
values
are
presented
for
each
exposure
duration
considered
in
the
assessment
(i.
e.,
short
term
and
intermediate
term
duration
exposures,
respectively).
C
Appendix
J/
Table
1:
Carbaryl
Residential
Pet
Risk
Assessment
For
Toddlers
Presents
the
risks
for
short
term
and
intermediate
term
toddler
exposure
after
contact
with
treated
pets.
C
Appendix
K:
Determination
of
Deposition
Factors
For
Carbaryl
Mosquito
Control
Uses
Presents
the
calculations
and
the
data
used
to
determine
the
amount
of
residues
deposited
in
treated
residential
areas
after
mosquito
control
applications
by
air
and
ground.
C
Appendix
L/
Table
1
:
Carbaryl
Postapplication
Residential
Mosquito
Control
Risk
129
Assessment
Inputs
Contains
each
numerical
input
utilized
in
the
calculation
of
the
residential
mosquito
control
postapplication
risk
values.
C
Appendix
L/
Table
2
:
Residue
Levels
Used
For
Carbaryl
Residential
Risk
Assessment
On
Turf
After
Aerial
Mosquito
Control
Application
Presents
the
turf
transferable
residue
values
used
for
the
dermal,
hand
to
mouth,
object
to
mouth,
and
soil
ingestion
risk
assessments.
Includes
daily
values
which
have
been
used
for
short
term
exposures
and
30
day
average
values
which
have
been
used
for
intermediate
term
exposures.
These
values
have
been
adjusted
for
deposition
from
ULV
aerial
application.
C
Appendix
L/
Table
3
:
Residue
Levels
Used
For
Carbaryl
Residential
Risk
Assessment
On
Turf
After
Ground
Mosquito
Control
Application
Presents
the
turf
transferable
residue
values
used
for
the
dermal,
hand
to
mouth,
object
to
mouth,
and
soil
ingestion
risk
assessments.
Includes
daily
values
which
have
been
used
for
short
term
exposures
and
30
day
average
values
which
have
been
used
for
intermediate
term
exposures.
These
values
have
been
adjusted
for
deposition
from
ULV
ground
application.
C
Appendix
L/
Table
4:
Adult
Noncancer
Risk
Values
For
Carbaryl
Residential
Risk
Assessment
on
Turf
After
Aerial
Mosquito
Control
Application
Presents
the
risks
for
short
term
and
intermediate
term
adult
dermal
exposures
in
on
turf
while
engaged
in
high
contact
activity
such
as
heavy
lawncare
("
On
Residential
Turf")
or
while
playing
golf
on
a
treated
course
after
the
area
has
been
treated
for
mosquito
control
using
aerial
equipment.
C
Appendix
L/
Table
5:
Adult
Noncancer
Risk
Values
For
Carbaryl
Residential
Risk
Assessment
on
Turf
After
Ground
Mosquito
Control
Application
Presents
the
risks
for
short
term
and
intermediate
term
adult
dermal
exposures
in
on
turf
while
engaged
in
high
contact
activity
such
as
heavy
lawncare
("
On
Residential
Turf")
or
while
playing
golf
on
a
treated
course
after
the
area
has
been
treated
for
mosquito
control
using
ground
equipment.
C
Appendix
L/
Table
8:
Toddler
Dermal
Risk
Values
For
Carbaryl
on
Turf
After
Aerial
Mosquito
Control
Application
Presents
the
risks
for
short
term
and
intermediate
term
toddler
dermal
exposures
on
turf
while
engaged
in
high
contact
activity
after
the
area
has
been
treated
for
mosquito
control
using
aerial
equipment.
C
Appendix
L/
Table
9:
Toddler
Dermal
Risk
Values
For
Carbaryl
on
Turf
After
Ground
Mosquito
Control
Application
Presents
the
risks
for
short
term
and
intermediate
term
toddler
dermal
exposures
on
turf
while
engaged
in
high
contact
activity
after
the
area
has
been
treated
for
mosquito
control
using
ground
equipment.
130
C
Appendix
L/
Table
10:
Toddler
Hand
to
Mouth
Risk
Values
For
Carbaryl
on
Turf
After
Aerial
Mosquito
Control
Application
Presents
the
risks
for
short
term
and
intermediate
term
toddler
hand
to
mouth
exposures
in
on
turf
while
engaged
in
high
contact
activity
after
the
area
has
been
treated
for
mosquito
control
using
aerial
equipment.
C
Appendix
L/
Table
11:
Toddler
Hand
to
Mouth
Risk
Values
For
Carbaryl
on
Turf
After
Ground
Mosquito
Control
Application
Presents
the
risks
for
short
term
and
intermediate
term
toddler
hand
to
mouth
exposures
in
on
turf
while
engaged
in
high
contact
activity
after
the
area
has
been
treated
for
mosquito
control
using
ground
equipment.
C
Appendix
L/
Table
12:
Toddler
Object
to
Mouth
Risk
Values
For
Carbaryl
on
Turf
After
Aerial
Mosquito
Control
Application
Presents
the
risks
for
short
term
and
intermediate
term
toddler
object
to
mouth
exposures
in
on
turf
while
engaged
in
high
contact
activity
after
the
area
has
been
treated
for
mosquito
control
using
aerial
equipment.
C
Appendix
L/
Table
13:
Toddler
Object
to
Mouth
Risk
Values
For
Carbaryl
on
Turf
After
Ground
Mosquito
Control
Application
Presents
the
risks
for
short
term
and
intermediate
term
toddler
object
to
mouth
exposures
in
on
turf
while
engaged
in
high
contact
activity
after
the
area
has
been
treated
for
mosquito
control
using
ground
equipment.
°
Appendix
L/
Table
14:
Toddler
Soil
Ingestion
Risk
Values
For
Carbaryl
on
Turf
After
Aerial
Mosquito
Control
Application
Presents
the
risks
for
short
term
and
intermediateterm
toddler
soil
ingestion
exposures
in
on
turf
while
engaged
in
high
contact
activity
after
the
area
has
been
treated
for
mosquito
control
using
aerial
equipment.
°
Appendix
L/
Table
15:
Toddler
Soil
Ingestion
Risk
Values
For
Carbaryl
on
Turf
After
Ground
Mosquito
Control
Application
Presents
the
risks
for
short
term
and
intermediateterm
toddler
soil
ingestion
exposures
in
on
turf
while
engaged
in
high
contact
activity
after
the
area
has
been
treated
for
mosquito
control
using
ground
equipment.
°
Appendix
L/
Table
16:
Toddler
Aggregate
Risk
Values
For
Carbaryl
on
Turf
After
Aerial
Mosquito
Control
Application
Presents
the
risks
for
short
term
and
intermediateterm
toddler
aggregate
exposures
in
on
turf
while
engaged
in
high
contact
activity
after
the
area
has
been
treated
for
mosquito
control
using
aerial
equipment.
°
Appendix
L/
Table
17:
Toddler
Aggregate
Risk
Values
For
Carbaryl
on
Turf
After
Ground
Mosquito
Control
Application
Presents
the
risks
for
short
term
and
intermediate
term
toddler
aggregate
exposures
in
on
turf
while
engaged
in
high
contact
activity
after
the
area
has
been
treated
for
mosquito
control
using
ground
equipment.
°
Appendix
M/
Table
1:
Summary
of
Carbaryl
Data
From
Ecology's
Post
Spray
Samples
(July
31
August
4,
2000)
Presents
summary
water
data
for
monitoring
conducted
by
the
Washington
State
Department
of
Ecology
in
Willapa
Bay
during
2000.
131
°
Appendix
M/
Table
2:
Summary
of
Carbaryl
Data
From
Shoalwater
Bay
Tribe
(July
17
&
19,
2000)
Presents
summary
water
data
for
monitoring
conducted
by
the
Shoalwater
Bay
Indian
Tribe
in
Willapa
Bay
during
2000.
[Note:
These
data
were
used
as
summarized
from
2001
Washington
State
Dept
of
Ecology
Report.]
°
Appendix
M/
Table
3:
Carbaryl
and
1
napthol
Concentrations
In
Willapa
Bay
PostSpray
Sediment
Presents
summary
sediment
data
for
monitoring
conducted
by
the
Washington
State
Department
of
Ecology
in
Willapa
Bay
during
1999.
°
Appendix
M/
Table
4:
Carbaryl
Concentrations
In
Day
60
Willapa
Bay
Pore
Water
Presents
summary
water
data
for
monitoring
conducted
60
days
after
spraying
by
the
Washington
State
Department
of
Ecology
in
Willapa
Bay
during
1999.
[Note:
Samples
were
collected
in
this
study
at
2
and
30
days
after
sampling
which
were
not
reported
due
to
analytical
problems.]
°
Appendix
M/
Table
5:
Carbaryl
Oyster
Harvest/
Beach
Play
Risk
Assessment
For
Adults
and
Toddlers
Presents
noncancer
and
cancer
risk
estimates
for
adults
and
toddlers
while
oyster
harvesting
or
playing
on
a
beach.
This
assessment
is
based
on
dermal
contact
with
contaminated
sediment
and
hand
to
mouth
behavior
for
toddlers.
The
highest
sediment
concentration
detected
in
any
data
available
to
the
Agency
was
used
to
assure
screening
level
nature
of
assessment.
°
Appendix
M/
Table
6:
Carbaryl
Oyster
Harvest/
Beach
Play
Risk
Assessment
For
Adults
and
Toddlers
Presents
noncancer
and
cancer
risk
estimates
for
adults
if
they
were
to
swim
in
Willapa
Bay.
All
calculations
were
completed
with
the
Agency's
SWIMODEL
(V2.0).
Results
and
model
inputs
are
included
in
this
table.
The
Agency
has
addressed
residential
postapplication
exposures
to
carbaryl
using
the
standard
set
of
scenarios
that
are
prescribed
in
current
guidance.
There
are
many
issues
associated
with
the
development
of
these
scenarios
and,
in
general,
residential
exposure
methods.
Readers
should
refer
to
the
guidance
documents
that
are
presented
above
for
further
information
concerning
the
development
of
scenarios
for
residential
exposure
assessment
purposes.
The
uncertainty
factors
are
similar
to
those
applied
to
the
residential
handler
assessments
described
above
(i.
e.,
100
for
both
short
term
and
intermediate
term
exposures).
Risk
Summary:
Adult
Short
term
MOEs
only
for
lawncare
(i.
e.,
heavy
yardwork)
exceed
the
Agency's
level
of
concern
on
the
day
of
application
(i.
e.,
43
to
88).
For
this
activity,
it
takes
1
and
5
days,
respectively
at
the
4
and
8
lb
ai/
acre
application
rates,
for
residues
to
dissipate
to
a
point
where
short
term
MOEs
are
$
100.
In
all
other
scenarios
considered,
short
term
MOEs
are
$
100
on
the
day
of
application.
These
other
scenarios
include
vegetable
gardening,
golfing,
tending
fruit
trees.
More
localized
exposures
that
occur
after
mosquito
control
or
from
exposures
associated
with
oyster
bed
treatments
are
also
included.
Intermediate
term
MOEs
were
calculated
using
30
day
average
exposures
and
the
dissipation
rate
for
carbaryl.
In
all
cases,
intermediate
term
MOEs
are
132
$
100.
Table
26
presents
the
postapplication
MOE
values
calculated
for
adults
after
lawn
and
home
garden
applications
of
carbaryl.
Table
26:
Summary
of
Carbaryl
Noncancer
Postapplication
Residential
MOEs
For
Adults
Scenario
Descriptor
Results
Short
term
MOE
on
Day
0
Days
Short
term
MOE
UF
Intermediateterm
MOE
Residential
Turf
(Lawncare)
Max
Rate
at
4
lb
ai/
A
88
1
842
Max
Rate
at
8
lb
ai/
A
43
5
412
Aerial
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
3700
231268
0
35463
2216454
Ground
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
7031
439409
0
67380
4211262
Golfing
Max
Rate
at
4
lb
ai/
A
1274
0
12297
Max
Rate
at
8
lb
ai/
A
624
0
6021
Aerial
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
53654
3353387
0
517764
32360224
Ground
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
101943
6371435
0
983751
61484426
Home
Garden
(Deciduous
Tree)
Very
Low
Exposure
(propping)
17373
0
53139
Low
Exposure
(irrigation,
scout,
weed)
1737
0
5314
High
Exposure
(harvest,
prune,
train,
tie,
thin)
579
0
1771
Home
Garden
(Fruiting
Vegetable)
Low
Exposure
(irrigation,
scout,
thin,
weed)
1758
0
9468
Medium
Exposure
(irrigation,
scout)
1256
0
6763
High
Exposure
(harvest,
prune,
stake,
tie)
879
0
4734
Oyster
Beds
Oyster
Harvest
967137
0
2680745
Swimming
293651
0
No
Data
133
Youth
aged
children
(10
to
12
years
old)
were
only
considered
in
the
home
garden
scenarios
per
Agency
guidance.
Short
term
MOEs
for
these
children
were
similar
to
those
calculated
for
adults
in
that
they
were
$
100
for
all
of
the
gardening
scenarios
considered.
Intermediate
term
MOEs
were
calculated
using
30
day
average
exposures
and
the
dissipation
rate
for
carbaryl.
In
all
cases,
intermediate
term
MOEs
are
$
100.
Table
27
below
summarizes
the
postapplication
MOE
values
calculated
for
youth
home
garden
applications
of
carbaryl.
Table
27:
Summary
of
Carbaryl
Noncancer
Postapplication
Residential
MOEs
For
Youth
Aged
Children
Scenario
Descriptor
Results
Short
term
MOE
on
Day
0
Days
Short
term
MOE
UF
Intermediateterm
MOE
Home
Garden
(Deciduous
Tree)
Very
Low
Exposure
(propping)
19408
0
59364
Low
Exposure
(irrigation,
scout,
weed)
1941
0
5936
High
Exposure
(harvest,
prune,
train,
tie,
thin)
647
0
1979
Home
Garden
(Fruiting
Vegetable)
Low
Exposure
(irrigation,
scout,
thin,
weed)
1964
0
10577
Medium
Exposure
(irrigation,
scout)
1403
0
7555
High
Exposure
(harvest,
prune,
stake,
tie)
982
0
5289
Toddler
(3
year
old)
MOEs
were
calculated
for
the
lawncare
and
pet
uses
of
carbaryl.
Table
28
presents
a
summary
of
the
MOE
estimates
for
toddlers.
Exposures
were
also
addressed
that
resulted
from
residential
application
of
carbaryl
as
a
mosquito
adulticide.
Toddler
MOEs
from
treated
turf
were
calculated
at
the
lower
and
upper
ends
of
the
maximum
application
rate
range
(i.
e.,
different
maximum
rates
of
4
to
8
lb
ai/
acre
were
specified
for
different
pests).
A
range
of
application
rates
were
also
considered
for
the
mosquito
control
uses.
Short
term
MOEs
from
exposure
to
treated
turf
(in
products
labeled
for
direct
application
to
turf)
were
<100
on
the
day
of
application
for
both
rates
considered
(i.
e.,
4
and
8
lb
ai/
acre).
In
fact,
short
term
MOEs
from
individual
pathways
were
not
$
100
for
any
turf
scenario
considered
on
the
day
of
application
except
for
the
soil
ingestion
component
of
the
turf
assessment
which
is
a
very
minor
contributor
to
overall
exposures.
As
a
reminder,
dermal,
hand
to
mouth,
and
object
to
mouth
exposure
pathways
were
also
considered.
Total
short
term
MOEs
(all
pathways)
were
$
100
at
the
lower
4
lb
ai/
acre
application
rate
14
days
after
application
and
18
days
at
the
higher
8
lb
ai/
acre
application
rate.
Dermal
and
hand
to
mouth
exposures
were
the
key
contributors
while
soil
ingestion
was
a
minor
contributor
to
the
total
MOE
estimates.
See
Appendix
H
for
more
detailed
information
on
how
each
exposure
pathway
contributed
to
the
overall
exposures.
Intermediate
term
MOEs
were
calculated
using
30
day
average
exposures
and
the
dissipation
rate
for
carbaryl.
For
134
both
rates,
intermediate
term
MOEs
were
<100.
Exposures
to
toddlers
were
also
considered
after
application
of
carbaryl
as
a
mosquito
adulticide.
Regardless
of
how
applications
are
made
(i.
e.,
by
ground
or
air),
both
short
term
MOEs
on
the
day
of
application
and
intermediate
term
MOEs
were
$
100.
See
Appendix
L
for
more
detailed
information
on
how
each
exposure
pathway
contributed
to
the
overall
exposures.
Ingestion
of
carbaryl
granules
is
also
a
potential
source
of
exposure
because
children
can
eat
them
if
they
are
found
in
treated
lawns
or
gardens.
This
scenario
is
considered
an
episodic
scenario
by
the
Agency
(i.
e.,
acute
dietary
endpoints
are
always
used).
The
concentration
of
carbaryl
in
granular
products
ranges
generally
from
2
to
10
percent.
If
this
information
is
coupled
with
the
body
weight
of
a
toddler
(15
kg),
the
endpoint
of
1
mg/
kg/
day
for
short
term
assessments
(which
is
also
the
same
value
used
for
the
APAD),
and
the
uncertainty
factor
of
100
the
amount
of
formulation
that
can
be
consumed
at
the
uncertainty
factor
MOE
level
can
be
calculated.
The
Agency
generally
presents
these
results
based
on
the
number
of
carbaryl
granules
that
can
be
ingested.
However,
the
number
of
homeowner
formulations
is
extensive
and
impossible
to
characterize
in
that
much
detail
so
a
general
weight
estimate
is
presented.
If
a
2
percent
formulation
is
ingested,
7.5
mg
represents
exposure
at
an
MOE
of
100
(i.
e.,
1.6
x
10
5
lb).
If
a
10
percent
formulation
is
ingested,
1.5
mg
represents
exposure
at
an
MOE
of
100
(i.
e.,
3.3
x
10
6
lb).
For
illustrative
purposes,
if
one
considers
a
2
percent
formulation
and
the
density
of
soil
(0.67
mL/
gram,
many
granulars
are
clay
based),
only
0.005
mL
of
formulation
would
need
to
be
ingested
to
have
a
risk
concern
(i.
e.,
7.5
mg
*
1g/
1000mg
*
0.67
mL/
gram).
Note
that
this
volume
is
orders
of
magnitude
less
than
a
teaspoon
of
granular
formulation
(i.
e.,
0.1%
of
a
teaspoon
where
a
tsp.
=
5
mL).
The
assessments
for
pet
uses
considered
dermal
and
nondietary
ingestion
exposures
and
also
calculated
total
MOEs.
Short
term
MOEs
for
pet
uses
were
<100
even
30
days
after
application
regardless
of
whether
the
formulation
used
was
a
dust,
liquid
or
collar.
This
trend
was
observed
for
each
separate
exposure
pathway
as
well
as
the
total
MOE
estimates.
Hand
to
mouth
and
dermal
exposures
are
approximately
equal
contributors
to
the
overall
estimates
for
each
product
type.
The
results
are
similar
for
the
intermediate
term
MOEs
for
each
scenario.
There
is
one
pet
use
which
is
also
considered
to
be
a
chronic
exposure
by
the
Agency.
Pet
collars
are
assumed
to
be
worn
all
of
the
time
so
chronic
exposure
can
potentially
occur.
The
chronic
MOE
for
pet
collars
mirrors
the
short
and
intermediate
term
results.
See
Appendix
J
for
more
detailed
information
on
how
each
exposure
pathway
contributed
to
the
overall
exposures.
The
assessments
for
beach
play
for
toddlers
after
oyster
bed
treatement
considered
dermal
and
nondietary
ingestion
exposures
and
also
calculated
total
MOEs.
Short
term
MOEs
were
>100
even
if
the
highest
monitored
sediment
concentration
value
from
any
study
available
to
the
Agency
was
used
as
the
basis
for
the
calculations.
The
intermediate
term
results
were
similar.
See
Appendix
M
for
more
information
on
how
each
pathway
contributed
to
the
overall
exposures.
135
Table
28:
Summary
of
Carbaryl
Noncancer
Postapplication
Residential
Aggregate
MOEs
For
Toddlers
Scenario
Descriptor
Results
Short
term
MOE
on
Day
0
Days
For
Short
term
MOE
UF
Intermediateterm
MOE
Chronic
MOE
Pet
Treatments
Liquids
2.0
+30
4
NA
Dusts
0.
02
+30
0.04
NA
Collars
18
+30
18
43
Residential
Turf
(High
Activity)
Max
Rate
at
4
lb
ai/
A
11
14
91
NA
Max
Rate
at
8
lb
ai/
A
5
18
45
NA
Aerial
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
448
27983
0
3826
239095
NA
Ground
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
851
53167
0
7269
454280
NA
Oyster
Beds
Beach
Play
29532
0
81859
NA
3.2.4
Residential
Postapplication
Exposure
and
Risk
Estimates
for
Cancer
The
residential
postapplication
exposure
and
cancer
risk
calculations
are
presented
in
this
section.
Cancer
risks
were
calculated
using
a
linear
low
dose
extrapolation
approach
in
which
a
Lifetime
Average
Daily
Dose
(LADD)
is
first
calculated
and
then
compared
with
a
Q1*
that
has
been
calculated
for
carbaryl
based
on
dose
response
data
in
the
appropriate
toxicology
study
(Q1*
=
8.75
x
10
4
(mg/
kg/
day)
1
).
Absorbed
average
daily
dose
(ADD)
levels
were
used
as
the
basis
for
calculating
the
LADD
values.
Section
2.1.3
above
describes
how
the
ADD
values
were
first
calculated
for
the
noncancer
MOE
calculations.
These
values
also
serve
as
the
basis
for
the
cancer
risk
estimates.
Dermal
and
inhalation
ADD
values
were
first
added
together
to
obtain
combined
ADD
values.
LADD
values
were
then
calculated
and
compared
the
Q1*
to
obtain
cancer
risk
estimates.
LADD
and
Cancer
Risk
Calculations:
The
use
of
dissipation
data
and
the
manner
in
which
daily
postapplication
dermal
exposure
values
were
calculated
were
inherently
different
than
with
handler
exposures.
Once
daily
exposure
values
were
determined,
the
calculation
of
LADD
(Lifetime
Average
Daily
Dose)
and
the
resulting
cancer
risks
use
the
same
algorithms
that
were
described
above
for
the
handler
exposures
(See
Section
2.1.4).
As
mentioned
previously,
the
Agency
has
defined
a
range
of
acceptable
cancer
risks
based
on
a
policy
issued
in
1996.
This
memo
refers
to
a
predetermined
quantified
"level
of
concern"
for
residential
carcinogenic
risk.
In
summary,
residential
carcinogenic
risks
that
are
1
x
10
6
or
lower
require
no
risk
management
action.
In
addition
to
the
cancer
risk
estimates
for
an
annual
frequency
of
1
time
per
year,
the
number
of
days
of
exposure
per
year
required
to
get
a
1x10
6
cancer
risk
have
136
been
calculated.
In
this
calculation,
the
1x10
6
cancer
risk
limit
was
divided
by
the
calculated
cancer
risk
for
each
scenario
for
a
single
day
of
exposure.
This
calculation
would
only
be
completed
for
situations
where
the
cancer
risks
were
less
than
1x10
6
on
the
day
of
application.
Cancer
Risk
Summary
All
of
the
cancer
risk
calculations
for
the
various
residential
carbaryl
assessments
are
included
in
Appendices
H,
I,
L
and
M
for
the
turf,
home
garden,
mosquito
adulticide,
and
oyster
treatment
scenarios,
respectively.
The
specifics
of
each
of
table
included
in
these
Appendices
are
described
below.
A
summary
of
the
results
for
each
scenario
considered
for
each
timeframe
is
also
provided
below.
C
Appendix
H/
Table
4:
Adult
Cancer
Risk
Values
For
Carbaryl
Residential
Risk
Assessment
on
Turf
Presents
the
risks
for
activities
on
turf
including
lawncare
and
golfing
at
the
two
application
rates
considered
in
the
assessment.
C
Appendix
I/
Tables
3:
Carbaryl
Residential
Postapplication
Adult
Cancer
Risk
Assessment
For
Deciduous
Tree
Crop
Group
Risk
values
are
presented
for
different
activities
in
home
tree
crops.
C
Appendix
I/
Tables
6:
Carbaryl
Residential
Postapplication
Adult
Cancer
Risk
Assessment
For
Fruiting
Vegetable
Crop
Group
Risk
values
are
presented
for
different
activities
in
home
vegetable
gardens.
°
Appendix
M/
Table
5:
Carbaryl
Oyster
Harvest/
Beach
Play
Risk
Assessment
For
Adults
and
Toddlers
Presents
noncancer
and
cancer
risk
estimates
for
adults
and
toddlers
while
oyster
harvesting
or
playing
on
a
beach.
This
assessment
is
based
on
dermal
contact
with
contaminated
sediment
and
hand
to
mouth
behavior
for
toddlers.
The
highest
sediment
concentration
detected
in
any
data
available
to
the
Agency
was
used
to
assure
screening
level
nature
of
assessment.
°
Appendix
M/
Table
6:
Carbaryl
Oyster
Harvest/
Beach
Play
Risk
Assessment
For
Adults
and
Toddlers
Presents
noncancer
and
cancer
risk
estimates
for
adults
if
they
were
to
swim
in
Willapa
Bay.
All
calculations
were
completed
with
the
Agency's
SWIMODEL
(V2.0).
Results
and
model
inputs
are
included
in
this
table.
For
all
scenarios
on
turf,
cancer
risks
are
in
the
10
8
range
or
less
on
the
day
of
application
when
a
single
reentry
event
per
year
during
lawncare
activities
is
evaluated.
For
home
gardening,
golfing
or
from
mosquito
control,
risks
are
slightly
lower
in
the
10
9
to
10
12
range
when
a
single
reentry
event
per
year
is
evaluated
on
the
day
of
application.
Table
29
below
summarizes
the
postapplication
risk
values
calculated
for
adults
after
applications
of
carbaryl.
Risk
managers
should
consider
these
values
represent
a
single
reentry
day
into
a
treated
area
over
each
year
of
a
50
year
lifetime
on
the
day
of
application
and
that
the
Agency
lacks
data
to
link
the
annual
frequency
of
reentry
activity
to
residential
applications.
As
with
the
residential
handler
risks
above,
the
Agency
calculated
the
number
of
exposure
days
needed
to
reach
a
risk
level
of
1x10
6
for
each
scenario
on
the
day
of
application,
values
range
from
20
to
over
365
days
per
year
while
most
exceed
365
days
per
year.
137
Table
29:
Summary
of
Carbaryl
Postapplication
Residential
Cancer
Risks
For
Adults
Scenario
Descriptor
Results
Risk
on
Day
0
Allowed
Days/
Year
Residential
Turf
(Lawncare)
Max
Rate
at
4
lb
ai/
A
2.5
x
10
8
40
Max
Rate
at
8
lb
ai/
A
5.1
x
10
8
20
Aerial
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
9.5
x
10
12
to
5.9
x
10
10
>365
Ground
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
5.0
x
10
12
to
3.1
x
10
10
>365
Golfing
Max
Rate
at
4
lb
ai/
A
1.7
x
10
9
>365
Max
Rate
at
8
lb
ai/
A
3.5
x
10
9
287
Aerial
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
6.5
x
10
13
to
4.1
x
10
11
>365
Ground
Mosquito
Adulticide
0.016
to
1.0
lb
ai/
A
3.4
x
10
13
to
2.1
x
10
11
>365
Home
Garden
(Deciduous
Tree)
Very
Low
Exposure
(propping)
2.5
x
10
10
>365
Low
Exposure
(irrigation,
scout,
weed)
2.5
x
10
9
>365
High
Exposure
(harvest,
prune,
train,
tie,
thin)
7.5
x
10
9
133
Home
Garden
(Fruiting
Vegetable)
Low
Exposure
(irrigation,
scout,
thin,
weed)
2.5
x
10
9
>365
Medium
Exposure
(irrigation,
scout)
3.5
x
10
9
289
High
Exposure
(harvest,
prune,
stake,
tie)
4.9
x
10
9
202
Oyster
Beds
Oyster
Harvest
4.
5
x
10
12
>365
Swimming
6.1
x
10
12
>365
3.2.5
Summary
of
Residential
Postapplication
Risk
Concerns
and
Data
Gaps
The
Agency
considered
a
number
of
exposure
scenarios
for
products
that
can
be
used
in
the
residential
environment
representing
different
segments
of
the
population
including
toddlers,
youthaged
children
and
adults.
Short
term
and
intermediate
term
noncancer
MOEs
were
calculated
for
all
scenarios.
Additionally,
cancer
risks
were
calculated
for
the
exposure
scenarios
involving
adults
where
methods
are
currently
available.
Cancer
risks
were
not
calculated
for
children
per
Agency
policy.
In
residential
settings,
the
Agency
does
not
use
REIs
or
other
mitigation
approaches
to
limit
exposures
because
they
are
viewed
as
impractical
and
not
enforceable.
As
such,
risk
estimates
on
the
day
of
application
are
the
key
concern.
138
The
Agency
has
short
term
risk
concerns
for
exposures
to
adults
doing
heavy
yardwork,
for
toddlers
playing
on
treated
lawns,
and
for
toddlers
that
have
contact
with
treated
pets.
Activities
associated
with
home
gardening
(e.
g.,
harvesting)
and
golfing
for
adults,
home
gardening
for
youthaged
children
or
any
age
or
activity
considered
in
the
adulticide
mosquito
control
or
oyster
assessment
do
not
have
risk
concerns
even
on
the
day
of
application
(i.
e.,
MOEs
$
100
on
the
day
of
application).
For
adults,
the
MOEs
for
heavy
yardwork
do
not
meet
or
exceed
risk
targets
(i.
e.,
MOE
=
100)
up
to
5
days
after
application.
For
toddlers,
the
Agency
has
concerns
for
pet
treatments
and
also
for
lawn
uses.
In
fact,
pet
uses
never
reach
acceptable
levels
even
30
days
after
application
and
not
until
18
days
at
the
maximum
application
rate
considered
on
turf.
Toddler
MOEs
from
pet
and
turf
uses
represent
total
exposures
from
many
pathways.
For
the
pet
uses,
dermal
and
hand
to
mouth
exposures
essentially
both
equally
contribute
to
the
overall
estimate.
For
the
turf
uses,
dermal
and
hand
to
mouth
exposures
are
also
the
key
contributors
to
the
overall
estimates.
The
Agency
does
not
have
intermediate
term
risk
concerns
for
adults
and
youth
aged
children
for
any
of
the
uses
considered
including
lawncare,
home
gardens,
golfing,
and
any
aspect
of
adulticide
mosquito
control
or
oyster
bed
uses.
In
contrast,
the
Agency
does
have
intermediateterm
risk
concerns
for
all
toddler
exposure
scenarios
considered
(i.
e.,
pet
treatments
and
lawncare
uses).
As
with
the
short
term
MOEs,
pet
and
turf
uses
represent
total
exposures
where
the
significant
contributions
to
overall
exposures
are
again
made
equally
from
the
dermal
and
hand
tomouth
exposure
pathways.
Cancer
risks
were
calculated
only
for
adults
and
were
found
to
be
in
the
10
8
to
10
12
range,
regardless
of
the
scenarios
considered,
on
the
day
of
application
(e.
g.,
lawncare,
golfing
and
gardening).
Risks
did
not
exceed
1x10
6
on
the
day
of
application
for
any
scenario
considered.
All
postapplication
cancer
risks
were
calculated
based
on
an
annual
frequency
of
1
exposure
per
year.
It
is
likely
that
additional
events
could
occur
but
data
linking
postapplication
activities
and
carbaryl
use
patterns
are
not
available.
To
address
this
issue,
the
Agency
calculated
the
number
of
exposures
that
can
occur
under
a
cancer
risk
ceiling
of
1x10
6
and
determined
that
from
20
days
per
year
to
exposures
every
day
of
the
year
could
occur
depending
upon
the
scenario.
Results
indicate
most
activities
can
occur
from
every
day
of
the
year
even
at
residue
levels
present
on
the
day
of
application..
Unlike
many
residential
risk
assessments,
the
postapplication
residential
assessment
for
carbaryl
is
based
on
a
number
of
chemical
specific
studies
that
have
been
used
to
calculate
risks
from
turf
uses
(e.
g.,
TTR
study)
and
in
gardens
(i.
e.,
DFR
data).
There
are
no
transferable
residue
data
available
for
pet
uses
which
is
a
key
data
gap.
Additional
data
could
potentially
be
used
to
refine
risk
estimates
for
the
other
settings
such
as
additional
DFR
data
on
different
crops
and
TTR
data
which
are
more
appropriate
for
hand
to
mouth
and
object
to
mouth
exposures.
The
Agency
combines
risks
resulting
from
total
exposures
to
individual
chemicals
when
it
is
likely
they
can
occur
simultaneously
based
on
the
use
pattern
and
the
behavior
associated
with
the
exposed
population.
For
carbaryl,
the
Agency
has
combined
risk
values
(i.
e.,
MOEs)
for
different
kinds
of
exposures
associated
with
the
turf
(dermal,
hand
to
mouth,
object
to
mouth,
and
soil
139
ingestion)
and
pet
scenarios
(dermal
and
hand
to
mouth).
These
represent
the
standard
set
of
exposures
that
are
typically
added
together
when
chemicals
are
used
on
turf
or
on
pets
because
it
is
logical
they
can
co
occur.
Typically,
the
Agency
only
adds
exposures
from
different
exposure
scenarios
together
(e.
g.,
spraying
and
gardening)
when
risks
from
both
are
not
already
a
concern.
For
carbaryl,
there
are
risk
concerns
for
many
residential
handler
scenarios
already
so
the
Agency
did
not
add
risk
values
from
any
postapplication
exposure
together
with
applicator
risks.
3.2.6
Recommendations
For
Refining
Residential
Postapplication
Risk
Assessment
In
order
to
refine
this
residential
assessment,
data
on
actual
use
patterns
including
rates,
timing,
and
the
kinds
of
tasks
that
are
required
to
better
characterize
carbaryl
risks.
Exposure
studies
for
many
cultural
practices
that
lack
data
or
that
are
not
well
represented
in
the
current
Agency
guidance
should
also
be
considered
based
on
the
data
gaps
identified
above
(e.
g.,
pet
uses).
Risk
managers
should
consider
that
the
risks
associated
with
current
label
generally
do
not
meet
Agency
targets,
especially
for
the
turf,
pet
and
high
exposure
garden
scenarios.
3.3
Residential
Risk
Characterization
3.3.1
Handler
Characterization
The
residential
handler
assessment
for
carbaryl
is
complex
in
that
calculations
were
completed
for
54
different
equipment
and
application
rate
scenarios.
Unlike
the
occupational
assessments,
only
short
term
exposures
were
considered
for
handlers
because
homeowner
use
patterns
are
not
believed
by
the
Agency
to
lead
to
intermediate
term
exposures
because
of
their
sporadic
nature.
Cancer
risks
were
also
calculated
using
a
linear,
low
dose
extrapolation
model
(i.
e.,
Q1*)
for
typical
residential
users
(1
event/
year).
Cancer
risks
were
also
considered
by
calculating
the
number
of
days
exposure
that
would
be
required
per
year
to
achieve
a
cancer
risk
of
1x10
6
to
illustrate
risk
levels
from
another
perspective.
All
totaled,
when
each
type
of
calculation
is
considered,
108
different
crop/
application
method
calculations
were
completed
for
residential
handlers.
The
data
that
were
used
in
the
in
the
carbaryl
residential
handler
assessment
represent
the
best
data
and
approaches
that
are
currently
available.
For
most
of
the
major
use
patterns,
carbarylspecific
data
or
data
generated
by
the
Outdoor
Residential
Exposure
Task
Force
were
used.
These
data
generally
are
considered
to
be
high
quality
by
the
Agency
and
the
best
source
of
information
available
for
the
scenarios
where
they
were
used.
Carbaryl
specific
data
were
used
to
address
the
garden
and
tree/
ornamental
scenarios
with
several
types
of
equipment
and
formulations
including
liquid
trigger
sprayers,
dusts,
and
liquid
sprays
using
low
pressure
handwand
and
hose
end
sprayers.
Carbaryl
specific
data
were
also
available
for
dusting
dogs.
The
ORETF
data
for
hoseend
sprayer
applications
to
turf
and
granular
applications
to
turf
were
also
used
to
address
those
scenarios.
In
the
remaining
scenarios,
the
Pesticide
Handlers
Exposure
Database
(PHED)
was
used
to
develop
the
unit
exposure
values.
The
quality
of
the
data
included
in
PHED
vary
widely
from
scenarios
that
meet
guideline
requirements
for
studies
to
others
where
a
limited
number
of
poor
quality
datapoints
are
available.
All
data
that
have
been
used
may
not
be
of
optimal
quality
but
140
represent
the
best
available
data.
The
inputs
for
application
rate
and
other
use/
usage
information
(e.
g.,
area
treated
and
frequency
of
use)
used
by
the
Agency
were
supported
by
the
available
carbaryl
labels
and
information
supplied
by
the
Aventis
Corporation
at
the
September
24,
1998
SMART
Meeting.
It
is
also
very
clear
that
because
carbaryl
is
such
as
widely
used
chemical
that
it
is
likely
every
potential
exposure
scenario
has
not
been
captured
because
of
difference
in
use
pattern.
As
more
refined
information
becomes
available
on
carbaryl
use,
the
Agency
will
refine
its
assessment
accordingly.
There
are
also
many
uncertainties
in
the
assessment
that
are
common
with
the
occupational
assessment
as
well.
These
factors
and
their
impacts
on
the
results
should
be
considered
as
well
in
the
interpretation
of
the
results
for
residential
handlers.
Section
2.3.1
provides
a
summary
of
these
issues.
In
summary,
with
respect
to
residential
handler
risks,
the
Agency
believes
that
the
values
presented
in
this
assessment
represent
the
highest
quality
results
that
could
be
produced
given
the
exposure,
use,
and
toxicology
data
that
are
available.
However,
there
are
certain
elements
where
additional
data
are
required.
For
example,
it
is
difficult
to
ascertain
where
on
a
distribution
certain
input
values
may
fall
because
the
distributional
data
for
exposure,
application
rates,
acres
treated
and
many
other
parameters
are
unrefined.
3.3.2
Postapplication
Characterization
Like
the
residential
handler
assessment
discussed
above,
the
postapplication
residential
assessment
for
carbaryl
is
also
complex
in
that
noncancer
MOE
calculations
were
required
based
on
the
recently
selected
endpoints
along
with
cancer
risk
calculations
using
a
linear,
low
dose
extrapolation
model.
Carbaryl
residues
persist
in
the
environment
as
indicated
in
the
available
DFR
and
TTR
data
for
periods
where
intermediate
term
as
well
as
short
term
noncancer
risk
estimates
are
required.
Cancer
risks
were
calculated
only
for
adults
per
current
Agency
policy.
The
general
population
can
be
exposed
through
many
different
pathways
that
result
from
uses
on
lawns
and
turf,
in
gardens,
on
ornamental
plants,
and
from
treated
pets.
People
can
also
be
exposed
from
mosquito
adulticide
applications
and
uses
in
oyster
beds.
Carbaryl
labels
do
not
currently
allow
for
indoor
residential
uses
(e.
g.,
crack
and
crevice).
Settings
where
such
exposures
could
occur
would
include
around
personal
residences
and
in
other
areas
frequented
by
the
general
public
including
parks,
ball
fields,
and
playgrounds.
To
represent
the
wide
array
of
possible
exposures,
the
Agency
relies
on
the
scenarios
that
have
been
defined
in
the
SOPs
For
Residential
Exposure
Assessment
and
accompanying
documents
such
as
the
overview
presented
to
the
FIFRA
Science
Advisory
Panel.
For
turf
uses,
the
Agency
considered
adults
and
toddlers
(3
year
olds)
in
the
assessments.
Adult
activities
included
lawncare/
maintenance
and
also
golfing.
Toddler
MOEs
were
calculated
for
playing
on
turf
(using
exposure
data
from
the
Jazzercize
model)
and
also
addressed
nondietary
ingestion
(hand/
object
to
mouth
and
soil
ingestion).
Exposures
from
tree
and
garden
uses
were
evaluated
by
considering
adults
and
youth
aged
children
(10
to
12
years
old)
doing
gardening
activities
such
as
weeding
and
harvesting
for
different
crop
groups.
Transfer
coefficients
from
the
fruiting
vegetable
crop
group
and
the
deciduous
tree
crop
group
were
used,
as
141
described
in
the
SOPs
For
Residential
Exposure
Assessment
to
represent
exposures
for
these
scenarios.
MOEs
from
treated
pets
were
evaluated
for
toddlers
again
for
whom
exposures
may
occur
from
dermal
contact
and
hand
to
mouth
behavior.
Adulticide
mosquito
applications
were
considered
by
first
defining
how
much
residues
are
deposited
on
the
ground
after
a
mosquito
control
application
then
using
the
same
methods
approaches
from
the
lawncare
assessment
to
address
adults
doing
heavy
yardwork
or
golfing
and
also
children
playing
on
treated
turf.
The
data
that
were
used
in
the
carbaryl
residential
postapplication
assessment
represent
the
best
data
and
approaches
that
are
currently
available.
To
the
extent
possible,
the
Agency
has
attempted
to
use
carbaryl
specific
data
such
as
with
the
dislodgeable
foliar
residue
(DFR)
data
used
for
the
garden
scenarios
and
the
turf
transferable
residue
(TTR)
data
used
for
the
dermal
component
of
the
turf
scenarios.
When
chemical
specific
data
were
unavailable,
the
Agency
used
the
current
approaches
for
residential
assessment,
many
of
which
include
recent
upgrades
to
the
SOPs.
For
example,
for
the
toddler
hand
to
mouth
calculations,
the
TTR
data
were
not
used
but
a
5
percent
transferability
factor
was
applied
to
calculate
residue
levels
appropriate
for
this
exposure
pathway.
Another
key
approach
to
consider
is
the
use
of
the
dermal
hug
approach
for
pet
products
which
was
proposed
at
the
September
1999
meeting
of
the
FIFRA
Science
Advisory
Panel.
Oyster
bed
uses
were
evaluated
based
on
guidance
from
Superfund
and
the
Agency's
SWIMODEL.
There
are
also
many
embedded
uncertainties
that
should
be
considered
in
the
interpretation
of
this
assessment
such
as
those
associated
with
the
use
of
Jazzercize
and
with
the
nondietary
ingestion
calculations.
Readers
should
consider
these
in
the
interpretation
of
the
overall
risk
estimates.
Readers
should
also
consider
the
screening
nature
of
the
SOPs
For
Residential
Exposure
Assessment
and
how
additional
data
could
refine
the
results.
Finally,
the
Agency
believes
that
the
values
presented
in
this
assessment
represent
the
highest
quality
results
that
could
be
produced
based
on
the
currently
available
postapplication
exposure
data.
Readers
of
this
document
should
consider
the
quality
of
individual
inputs
when
interpreting
the
results
and
make
decisions
accordingly.
It
is
difficult
to
ascertain
where,
on
a
distribution,
the
calculated
values
fall
because
the
distributional
data
for
exposure,
residue
dissipation
and
many
other
parameters
are
unrefined.
The
Agency
does
believe,
however,
that
the
risks
represent
conservative
estimates
of
exposure
because
maximum
application
rates
are
used
to
define
residue
levels
upon
which
the
calculations
are
based.
Additionally,
estimates
are
thought
to
be
conservative
even
when
measures
of
central
tendency
(e.
g.,
most
transfer
coefficients
are
thought
to
be
central
tendency)
are
used
because
values
that
would
be
considered
to
be
in
the
lower
percentile
aspect
of
any
input
parameter
have
not
been
used
in
the
calculations.
Appendix
A:
Use
Information
For
Carbaryl
Quantitative
Usage
Analysis
for
Carbaryl
Case
Number:
0080
PC
Code:
56801
Date:
July
21,
1998
Analyst:
Frank
Hernandez
Based
on
available
pesticide
survey
usage
information
for
the
years
of
1987
through
1996,
an
annual
estimate
of
carbaryl
total
domestic
usage
averaged
approximately
two
and
one
half
million
pounds
active
ingredient
(a.
i.)
for
over
one
and
one
half
million
acres
treated.
Carbaryl
is
an
insecticide
with
its
largest
markets
in
terms
of
total
pounds
active
ingredient
allocated
to
pecans
(12%),
apples
(9%),
grapes(
6%),
oranges
(5%),
alfalfa
(5%),
and
corn
(4%).
Most
of
the
usage
is
in
AR,
CA,
GA,
IL,
IN,
MI,
MS,
OH,
OK,
and
TX.
Crops
with
a
high
percentage
of
the
total
U.
S.
planted
acres
treated
include
avocados
(67%),
Chinese
cabbage
(57%),
asparagus
(43%),
cranberries
(39%),
and
Brussels
sprouts
(33%).
Crops
with
less
than
1
percent
of
the
crop
treated
include
alfalfa,
dry
beans,
canola,
corn,
cotton,
flax,
oats,
pasture,
green
peas,
safflower,
sod,
sorghum,
soybeans,
sugar
cane,
sunflowers,
sweet
corn,
walnuts,
wheat,
and
woodland.
Site
Acres
Grown
(000)
Acres
Treated
(000)
%
of
Crop
Treated
LB
AI
Applied
(000)
Average
Application
Rate
States
of
Most
Usage
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
lb
ai/
acre/
y
r
#appl
/
yr
lb
ai/
A/
appl
(%
of
total
lb
ai
used
on
this
site)
Alfalfa
23,949
120
263
0.50
1.10
130
365
1.1
1.0
1.1
NE
SD
OK
MT
ND
IL
77%
Almonds
429
7
16
1.72
3.61
16
49
2.1
1.0
2.1
CA
100%
Apples
572
131
175
22.92
30.59
230
282
1.8
1.4
1.2
WA
MI
NY
CA
CT
IN
77%
Asparagus
88
38
77
43.35
86.69
46
117
1.2
1.3
0.9
MI
WA
97%
Avocados
82
55
70
66.93
85.18
1
2
0.0
1.5
0.0
Beans,
Dry
1,802
12
51
0.65
2.86
6
28
0.5
1.0
0.5
CA
ND
CO
88%
Site
Acres
Grown
(000)
Acres
Treated
(000)
%
of
Crop
Treated
LB
AI
Applied
(000)
Average
Application
Rate
States
of
Most
Usage
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
lb
ai/
acre/
y
r
#appl
/
yr
lb
ai/
A/
appl
(%
of
total
lb
ai
used
on
this
site)
Beans,
Lima,
Fresh
6
1
2
12.49
29.88
1
2
1.1
1.2
0.9
GA
100%
Beans,
Snap,
Fresh
81
11
17
14.12
21.03
16
23
1.4
1.6
0.9
NC
FL
84%
Beans,
Snap,
Proc.
228
24
36
10.39
15.83
28
43
1.2
1.6
0.7
IL
St
OR
83%
Beets
12
2
3
16.87
27.45
1
2
0.5
1.0
0.5
WI
TX
OR
94%
Blackberries
5
1
2
28.39
44.05
2
4
1.7
1.0
1.7
OR
100%
Blueberries
59
13
26
22.43
44.85
26
53
2.0
1.2
1.7
ME
MI
83%
Broccoli
114
5
10
4.43
8.86
4
8
0.8
1.0
0.8
CA
OR
TX
88%
Brussels
Sprouts
3
1
2
33.33
66.67
1
2
1.0
1.1
0.9
Cabbage,
Chinese
9
5
7
57.47
80.46
1
2
0.2
1.1
0.2
CA
90%
Cabbage,
Fresh
84
1
4
1.78
4.40
2
6
1.6
1.6
1.0
NC
NY
84%
Canola
39
0
2
0.31
4.64
0
1
0.5
1.0
0.5
MT
100%
Cantaloupes
113
8
11
7.27
9.39
8
13
0.9
1.1
0.8
CA
IL
GA
TX
83%
Carrots
107
4
6
3.67
5.75
9
23
2.3
2.5
0.9
WI
MI
MN
88%
Cauliflower
58
1
2
1.55
3.60
1
2
1.1
1.0
1.1
OR
CA
WA
83%
Celery
37
1
2
2.97
6.13
2
4
1.8
1.8
1.0
MI
WI
89%
Cherries,
Sweet
47
12
17
25.29
36.45
32
46
2.7
1.4
1.9
WA
MI
CA
84%
Cherries,
Tart
49
6
11
11.79
23.59
13
27
2.3
1.3
1.9
MI
NY
88%
Site
Acres
Grown
(000)
Acres
Treated
(000)
%
of
Crop
Treated
LB
AI
Applied
(000)
Average
Application
Rate
States
of
Most
Usage
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
lb
ai/
acre/
y
r
#appl
/
yr
lb
ai/
A/
appl
(%
of
total
lb
ai
used
on
this
site)
Citrus,
Other
51
2
3
2.98
5.65
5
12
3.2
1.8
1.8
FL
86%
Collards
11
0
1
3.72
10.13
0
1
0.9
1.0
0.9
NJ
88%
Corn
72,284
82
164
0.11
0.23
110
228
1.3
1.3
1.0
MO
NE
MS
IN
GA
IL
51%
Cotton
12,689
26
77
0.20
0.61
32
94
1.2
1.1
1.1
TN
MS
TX
CA
83%
Cranberries
29
11
24
38.97
83.65
23
48
2.0
1.0
2.0
WI
MA
95%
Cucumbers
146
20
46
14.03
31.83
23
51
1.1
1.0
1.1
NC
OH
SC
NY
VA
DE
73%
Cucumbers,
Proc.
117
5
11
4.69
9.37
7
15
1.3
2.2
0.6
NC
MI
85%
Eggplant
119
11
25
8.87
20.59
22
54
2.0
2.1
1.0
FL
NJ
TX
IL
OR
CA
64%
Flax
188
1
2
0.46
0.91
1
2
1.1
1.0
1.1
ND
100%
Grapefruit
194
8
11
4.05
5.59
18
20
2.3
1.6
1.4
FL
TX
95%
Grapes
825
64
97
7.77
11.81
150
217
2.3
1.7
1.4
NY
CA
OR
PA
MI
AR
77%
Hay,
Other
33,427
91
267
0.27
0.80
87
273
1.0
1.2
0.8
TX
SD
FL
NC
CA
LA
81%
Hazelnuts
(Filberts)
27
1
3
3.90
12.18
3
8
2.5
1.0
2.5
Lemons
63
2
4
2.77
6.55
6
14
3.4
1.3
2.7
CA
91%
Lettuce,
Head
212
7
17
3.08
8.10
8
22
1.3
1.2
1.1
CA
82%
Lots/
Farmsteads/
etc
24,815
58
152
0.23
0.61
60
174
1.0
2.5
0.4
MA
AZ
FL
PA
TX
KY
62%
Melons,
Honeydew
27
5
12
19.09
43.69
4
10
0.9
1.2
0.7
CA
100%
Site
Acres
Grown
(000)
Acres
Treated
(000)
%
of
Crop
Treated
LB
AI
Applied
(000)
Average
Application
Rate
States
of
Most
Usage
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
lb
ai/
acre/
y
r
#appl
/
yr
lb
ai/
A/
appl
(%
of
total
lb
ai
used
on
this
site)
Nectarines
29
4
7
12.11
24.22
15
30
4.2
1.1
3.8
Oats/
Rye
6,133
8
18
0.13
0.29
6
13
0.7
1.0
0.7
MN
MS
ND
TX
MT
MI
77%
Okra
3
1
3
32.36
94.03
2
6
1.9
1.0
1.9
TX
84%
Olives
32
3
5
9.61
15.42
16
26
5.3
1.0
5.3
CA
100%
Onions,
Dry
157
6
18
3.71
11.36
23
72
4.0
7.0
0.6
MI
100%
Oranges
867
28
42
3.27
4.89
130
194
4.6
1.3
3.4
CA
FL
99%
Other
Crops
2,515
35
43
1.39
1.70
63
156
1.8
1.3
1.4
CA
MA
TX
NJ
WA
MI
75%
Pasture
86,960
27
69
0.03
0.08
25
77
0.9
1.0
0.9
NC
TX
SC
NE
LA
80%
Peaches
212
32
38
15.10
18.05
96
203
3.0
2.9
1.0
GA
CA
TX
OK
SC
MI
68%
Peanuts
1,610
48
96
2.99
5.99
53
107
1.1
1.4
0.8
GA
TX
NC
AL
VA
84%
Pears
78
2
5
2.92
6.43
3
8
1.5
1.5
1.0
WA
OR
CA
PA
NY
OH
73%
Peas,
Dry
249
6
22
2.52
8.97
6
22
1.0
1.0
1.0
WA
ID
TX
93%
Peas,
Green
386
6
28
1.59
7.13
9
40
1.5
1.0
1.5
MN
OR
83%
Peas,
Green,
Proc.
329
2
17
0.62
5.23
3
25
1.5
1.0
1.5
OR
100%
Pecans
488
95
115
19.53
23.51
290
610
3.0
2.2
1.4
GA
TX
OK
MS
AR
84%
Peppers,
Bell
55
6
11
10.15
20.30
9
22
1.5
1.7
0.9
FL
CA
MI
90%
Peppers,
Sweet
77
10
23
12.95
29.95
14
31
1.3
1.0
1.3
CA
FL
KY
LA
IL
80%
Site
Acres
Grown
(000)
Acres
Treated
(000)
%
of
Crop
Treated
LB
AI
Applied
(000)
Average
Application
Rate
States
of
Most
Usage
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
lb
ai/
acre/
y
r
#appl
/
yr
lb
ai/
A/
appl
(%
of
total
lb
ai
used
on
this
site)
Pistachios
52
9
20
16.84
38.06
32
72
3.6
1.0
3.6
Plums
64
3
6
4.68
9.36
12
23
3.8
1.0
3.8
CA
81%
Potatoes
1,421
24
38
1.70
2.68
34
50
1.4
1.7
0.8
ND
WA
MI
ID
FL
NY
59%
Pumpkins
36
11
20
31.21
56.11
37
66
3.2
1.6
2.0
IL
PA
IN
OH
83%
Raspberries
11
0
1
3.57
9.84
1
3
2.8
1.0
2.8
OR
MI
92%
Rice
2,921
33
40
1.15
1.37
41
58
1.2
1.1
1.1
TX
CA
80%
Safflower
113
1
7
0.98
5.96
0
3
0.4
1.0
0.4
CA
100%
Sod
152
0
7
0.14
4.28
0
15
2.2
1.0
2.2
TX
NH
100%
Sorghum
11,280
23
47
0.21
0.41
31
62
1.3
1.2
1.1
MO
KS
TX
LA
NE
MS
75%
Soybeans
62,879
101
210
0.16
0.33
86
174
0.9
1.0
0.9
MN
NE
SD
MS
NC
IL
60%
Squash
53
6
14
11.25
26.77
8
19
1.4
1.0
1.4
NJ
FL
MI
CA
NY
TX
90%
Strawberries
51
8
12
16.02
23.62
24
55
2.9
2.1
1.4
CA
FL
NC
PA
81%
Sugar
Beets
1,415
23
54
1.60
3.80
34
126
1.5
1.1
1.3
CA
TX
WA
MN
OR
84%
Sugarcane
852
0
1
0.04
0.07
0
0
0.2
1.1
0.1
FL
100%
Sunflower
2,745
11
40
0.40
1.47
8
31
0.7
1.1
0.7
SD
ND
92%
Sweet
Corn,
Fresh
233
9
17
3.84
7.12
28
52
3.1
2.5
1.3
CA
MI
IL
82%
Sweet
Corn,
Proc.
544
3
21
0.49
3.81
8
63
3.0
2.9
1.1
IL
100%
Site
Acres
Grown
(000)
Acres
Treated
(000)
%
of
Crop
Treated
LB
AI
Applied
(000)
Average
Application
Rate
States
of
Most
Usage
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
lb
ai/
acre/
y
r
#appl
/
yr
lb
ai/
A/
appl
(%
of
total
lb
ai
used
on
this
site)
Sweet
Potatoes
85
16
35
18.47
40.90
25
55
1.6
1.0
1.6
LA
MS
NC
82%
Tobacco
695
10
20
1.50
2.85
18
44
1.7
1.5
1.1
NC
KY
SC
TN
IN
84%
Tomatoes,
Fresh
136
7
15
5.40
10.80
14
35
1.9
2.6
0.7
CA
FL
TX
87%
Tomatoes,
Proc.
329
48
88
14.47
26.86
72
135
1.5
1.3
1.2
CA
97%
Walnuts
205
1
4
0.54
1.82
2
8
2.1
1.1
1.9
CA
100%
Watermelons
258
33
38
12.71
14.79
16
33
0.5
1.0
0.5
FL
IN
MS
TX
GA
76%
Wheat,
Spring
20,799
24
48
0.11
0.23
16
32
0.7
1.0
0.6
ND
MN
MT
88%
Wheat,
Winter
45,854
50
106
0.11
0.23
44
78
0.9
1.0
0.8
KY
NC
TX
WY
OR
MD
67%
Woodland
62,825
31
72
0.05
0.11
26
54
0.8
1.2
0.7
PA
MI
FL
ND
OH
IA
79%
Total
1659.6
2464
2517.2
3926
COLUMN
HEADINGS
Wtd
Avg
=
Weighted
average
the
most
recent
years
and
more
reliable
data
are
weighted
more
heavily.
Est
Max
=
Estimated
maximum,
which
is
estimated
from
available
data.
Average
application
rates
are
calculated
from
the
weighted
averages.
NOTES
ON
TABLE
DATA
Usage
data
primarily
covers
1987
1996.
Calculations
of
the
above
numbers
may
not
appear
to
agree
because
they
are
displayed
as
rounded
to
the
nearest
1000
for
acres
treated
or
lb.
a.
i.
(Therefore
0
=
<
500)
to
two
decimal
percentage
points
for
%
of
crop
treated.
Other/
Crop
Groups
Citrus,
Other
includes
kumquats,
limes,
tangelos,
and
tangerines.
Other
Crops
include
ornamentals,
popcorn,
rapeseed/
canola,
and
safflower.
SOURCES:
EPA
data,
USDA,
and
National
Center
for
Food
and
Agricultural
Policy.
R.
E.
D.
Use
Profile
Report
A.
Chemical
Overview
Chemical
Name:
Carbaryl
Case
No:
0080
Chemical
Code:
056801
B.
Use
Profile
Type
of
Pesticide:
Acaricide/
Insecticide
and
Plant
regulator
Mode
of
Action:
Acetylcholine
esterase
inhibitor
Use
Sites:
Terrestrial
Food
Crop
Cucurbits
Cumber,
Melons,
Chinese
okra,
pumpkin,
and
squash
Flavoring
and
Spice
Crops
Dill
Fruiting
Vegetables
Eggplant
and
Pepper
Grain
Crops
Prosso
millet
Leafy
and
Stem
Vegetables
Beets,
Broccoli,
Brussels
sprouts,
Cabbage,
Chinese
cabbage,
Cauliflower,
Celerey,
Swiss
chard,
Collards,
Dandelion,
Endive
(Escarole),
Hanover
Salad,
Kale,
Kohlrabi,
Lettuce
(Head,
Crisphead
types,
Leaf
types),
Mustard,
Parsley,
Rhubarb,
and
Spinach
Miscellaneous
Fruits
Avocado,
Olive,
Pricklypear
Miscellaneous
Vegetables
Asparagus
Nut
Crops
Almond,
Chestnut,
Filbert
(Hazelnut),
Pecan,
Pistachio,
and
Walnut
(English/
black)
Pome
Fruits
Crabapple,
pear,
and
quince
Root
Crop
Vegetables
Beets,
Carrot
(including
tops),
Horseradish,
Radish,
Rutabaga,
Salsify,
and
Sweet
Potato
Small
Fruits
Blackberry,
Blueberry,
Boysenberry,
Caneberries,
Cranberry,
Dewberry,
Loganberry,
Raspberry
(Black,
Red),
and
Strawberry
Specialized
Field
Crops
Okra
Stone
Fruits
Apricot,
Cherry,
Nectarine,
Peach,
Plum,
and
Prune
Terrestrial
Food+
Feed
Crop
Citrus
Fruits
Citrus
fruits
Crops
Grown
for
Oil
Field
corn,
Flax,
and
Sunflower
Fiber
Crops
Flax
Fruiting
Vegetables
Tomato
Grain
Crops
Field
corn,
Rice,
Sorghum
and
Wheat
Groups
of
Agricultural
Crops
Which
Cross
Established
Crop
Groupings
Cotton,
Peanuts,
Peas,
Sorghum,
Soybeans,
and
Vegetables
Leafy
and
Stem
Vegetables
Mustard
and
Turnip
Nut
Crops
Almond,
and
Tree
nuts
Pome
Fruits
Apple
and
Pome
Fruits
Root
Crop
Vegetables
Parsnip,
White/
Irish
potato,
Salsify,
and
Turnip
Seed
and
Pod
Vegetables
Beans
(Dried
type),
Succulent
beans
(Lima
and
Snap),
Cowpea/
Blackeyed
pea,
Cowpea/
Sitao,
Lentils,
Peanuts,
Peas
(Dried
type),
Field
peas,
Southern
peas,
Succulent
peas,
and
Soybeans
(edible)
Small
Fruits
Grapes
and
Small
fruits
Specialized
Field
Crops
Pop
corn,
Sweet
corn,
and
Sunflower
Sugar
Crops
Sugar
beet
Terrestrial
Feed
Crop
Forage
Grasses
Corn,
Grass
forage/
fodder/
hay,
Millet
(Proso),
Pastures,
Rangeland,
Rice,
Sorghum,
and
Wheat
Forage
Legumes
and
Other
Nongrass
Forage
Crops
Alfalfa,
Clover,
Cotton,
and
Trefoil
Grain
Crops
Proso
millet
Groups
of
Agricultural
Crops
Which
Cross
Established
Crop
Groupings
Grasses
grown
for
seed
Terrestrial
non
food
crop
Agricultural
Uncultivated
Areas
Agricultural
fallow/
idleland
and
Agricultural
rights
of
way/
fencerows/
hedgerows
Commercial/
Industrial/
Institutional
Premises
and
Equipment
Fiber
Crops
Forest
Trees
Christmas
tree
plantations
Groups
of
Agricultural
Crops
Which
CrossEstablished
Crop
Groupings
Fruits
(unspecified)
Miscellaneous
Fruits
Longan
and
Mango
Nonagricultural
Uncultivated
Areas
Outdoor
buildings/
structures,
rights
of
way/
fencerows/
hedgerows,
uncultivated
areas/
soils,
and
recreational
areas
Ornamental
Lawns
and
Turf
Commercial/
Industrial
lawns,
Golf
course
turf,
Ornamental
sod
farm
(turf),
and
recreational
area
lawns
Specialized
Field
Crops
Tobacco
Wide
Area/
General
Outdoor
Treatments
Fencerows/
Hedgerows,
Urban
areas,
and
Wide
area/
General
outdoor
treatment
(Public
health
use)
Terrestrial
non
food+
outdoor
residential
Nonagricultural
Uncultivated
Areas
Rights
of
way/
Fencerows/
Hedgerows
Ornamental
Herbaceous
Plants
Ornamental
Lawns
and
Turf
Ornamental
Nonflowering
Plants
Ornamental
Woody
Shrubs
and
Vines
Ornamental
and/
or
Shade
Trees
Wide
Area/
General
Outdoor
Treatments
Fencerows/
Hedgerows
Terrestrial+
Greenhouse
non
food
crop
Ornamental
Herbaceous
Plants
Ornamental
Woody
Shrubs
and
Vines
Ornamental
and/
or
Shade
Trees
Aquatic
food
crop
Aquatic
Sites
Commercial
fishery
water
systems
Grain
Crops
Rice
Small
Fruits
Cranberry
Aquatic
non
food
industrial
Aquatic
Sites
Drainage
systems
Forestry
Forest
Trees
Forest
plantings
(Reforestation
programs,
tree
farms,
tree
plantations,
etc),
forest
trees
(all
or
unspecified),
maple
(forest),
and
Shelterbelt
plantings
Outodoor
residential
Households/
Domestic
Dwellings
Outdoor
premises
Ornamental
Herbaceous
Plants
Ornamental
Lawns
and
Turf
Residential
lawns
Pets
Pet
living/
sleeping
quarters
Indoor
food
Poultry
Egg/
Meat
Indoor
non
food
Pets
Target
Pests
for
Single
Active
Ingredient:
Invertebrates
(insects
and
related
organisms);
Adelgid
(Cooley
spruce
gall)
Ataenius
(Black
turfgrass
Ants
(Carpenter,
Fire,
Imported
fire)
Aphids
(Apple,
Balsam
twig,
Black
cherry,
Blackmargined,
Cooley
spruce
gall,
Eastern
spruce
gall,
Elm
leaf,
European
raspberry,
Filbert,
Gall,
Mealy
plum,
Rose,
Rosy
apple,
Wooly?,
Wooly
apple)
Appleworm
(Lesser)
Armyworm
(Fall,
True,
Western
yellowstriped,
Yellowstriped)
Bagworm
Bees
Beetle
(Aparagus,
Bean
leaf,
Beet
leaf,
Blister,
Cereal
leaf,
Chafer,
Colorado
potato,
Corn
rootworm,
Cucumber,
Darkling,
Darkling
ground?,
Elm
bark,
Elm
leaf,
Engraver,
European
alfalfa,
Flea,
Fuller
rose,
Green
june,
Ips
engraver,
Japanese,
June,
Litter,
May,
Mexican
bean,
Mountain
pine,
Rose,
Roundheaded
pine,
Sap,
Spruce
bark?,
Spruce?,
Striped
blister,
Sunflower,
Tobacco
flea,
Tortoise,
Western
pine,
Whitefringed,
Willow
leaf)
Billbugs
(Bluegrass)
Borer
(European
corn,
Lesser
peachtree,
Limabean
pod,
Locust,
Olive
ash,
Peach
twig,
Southwestern
corn,
West
Indian
sugarcane
root)
Budworm
(Jack
pine,
Spruce,
Tobacco,
Western
spruce)
Bug
(Bed,
Black
Grass,
Boxelder,
Chinch,
Harlequin,
Lace,
Lygus,
Plant,
Squash,
Stink,
Tarnished
plant)
Cabbageworm
(Imported)
Cankerworm
(Fall,
Spring)
Casebearer
(Pecan
nut)
Caterpillar
(Alfalfa,
Eastern
tent,
Forest
tent,
Oleander,
Painted
lady,
Puss,
Range,
Redhumped,
Saltmarsh,
Spiny
elm,
Spring
elm,
Tent,
Thistle
butterfly,
Velvetbean,
Walnut,
Woolybear)
Centipedes
Chafer
(European,
Rose)
Chiggers
(Redbugs)
Cicada
(Apache,
Periodical)
Clipper
(Strawberry)
Cloverworm
(Green)
Cockroach
(American,
Australian,
Brown,
Smoky
brown)
Colaspis
(Grape)
Crickets
(Mole,
Morman,
Snowy
tree)
Curculio
(Cowpea,
Plum)
Cutworm
(Army,
Citrus,
Cotton,
Western
bean)
Earwigs
(European)
Earworm
(Corn)
Firebrats
Fireworm
(Cranberry,
Yellowheaded)
Fleahopper
(Cotton)
Fleas
Fly
(Cherry
fruit,
European
crane,
Rangeland
crane)
Forester
(Eightspotted)
Fruitworm
(Cherry,
Cranberry,
Green,
Raspberry,
Sparganothis,
Strawberry,
Tomato)
Girdler
(Cranberry,
Twig)
Grasshoppers
Grubs
(White)
Hornworms
(Poinsettia,
Sweet
potato,
Tobacco,
Tomato)
Leafcutter
(Maple)
Leaffolder
(Grape)
Leafhopper
(Aster,
Avocado,
Cotton,
Potato,
Prune,
Redbanded,
Three
cornered
alfalfa,
White
apple)
Leafminer
(Alfalfa
blotch,
Azalea,
Birch,
Boxwood,
Holly,
Oak,
Tentiform)
Leafroller
(Avocado,
Filbert,
Fruittree,
Grape,
Oak,
Omnivorous,
Redbanded,
Strawberry,
Variegated)
Leaftier
(Omnivorous)
Leafworm
(Cotton)
Lecanium
(European
fruit)
Lice
Looper
(Alfalfa,
Pine,
Striped
grass,
Western
hemlock)
Maggot
(Apple,
Blueberry)
Maker
(Hackberry
nipplegall)
Mapleworm
(Greenstriped)
Mealworm
(Lesser)
Mealybug
(Apple,
Cherry)
Melonworm
Midges
(Gall)
Millipedes
Mites
(Apple
rust,
Chicken,
Citrus
rust,
Eriophyid,
Fuschia
gall,
Fuschia?,
Northern
fowl,
Pear
rust,
Pearleaf
blister)
Moth
(Browntail,
Codling,
Cyprus
tip,
Diamondback,
Douglas
fir
tussock,
European
pine
shoot,
Eyespotted
bud,
Grape
berry,
Gypsy,
Holly
bud,
Lawn,
Lucerne,
Maple
shoot,
Nantucket
pine
tip,
Oak,
Oriental
fruit,
Pitch
pine
tip,
Subtropical
pine
tip,
Sunflower,
Tussock,
Western
tussock)
Mosquito
Needleminers
(Jeffrey
pine,
Spruce)
Notcher
(Little
leaf)
Oakworm
(Orangestriped,
Redhumped)
Orangedog
(California)
Orangeworm
(Navel)
Pandemis
(Apple)
Peanutworm
(Rednecked)
Pearslug
(California)
Phylloxera
(Pecan
leaf?,
Pecan?)
Pickleworm
Pillbug/
Sowbugs
Pinworm
(Tomato)
Prominent
(Saddled)
Psylla
(Pear)
Roseslug
Sawfly
(European
apple,
Pear,
Pine,
Raspberry)
Scale
(Black,
Brown
soft,
Calico,
California
red,
Citricola,
Citrus
Snow,
Forbes,
Frosted,
Lecanium,
Olive,
Oystershell,
Red,
San
Jose,
Yellow)
Scorpions
Shrimp
(Ghost,
Mud,
Tadpole)
Shuckworm
(Hickory)
Silverfish
Skeletonizer
(Oak,
Western
Grapeleaf)
Skipper
(Essex,
Fiery)
Spanworm
(Elm)
Spiders
Spinx
(Catalpa)
Spittlebug
(Meadow,
Pecan,
Pine)
Springtails
Sucker
(Apple)
Suckfly
Thornbug
Thrips
Ticks
(Amblyomma
spp.,
Bear,
Blacklegged,
Brown
dog,
Deer,
Fowl,
Ixodes
spp.,
Lone
star)
Tortrix
(Orange)
Treehoppers
Wasps
(Gall)
Webworm
(Fall,
Lesser,
Mimosa,
Sod)
Weevil
(Alfalfa,
Bluegrass,
Chestnut
nut,
Citrus
root,
Clover
head,
Cotton
boll,
Egyptian
alfalfa,
Hyperodes,
Pea
Leaf?,
Pea?,
Pecan,
Strawberry
bud?,
Strawberry?,
Sugarcane
rootstalk
borer,
Sunflower
stem,
Sweet
potato,
Yellow
poplar)
Whiteflies
Worm
(Filbert)
Weeds
Aster
Blessed
thistle
Boxelder
Plant
regulator
abscission
agen,
flower
inhibitor,
fruit
thinning,
inhibit
fruiting
White
ash
Yellow
poplar
Formulation
Types
Registered
(%
AI):
Technical
Grade
Material
Form
not
identified/
solid
99.0000%
Manufacturing
product
dust
80.0000%
Emulsifiable
concentrate
97.5000%
End
Use
Product
Bait/
solid
10.0400%
Emulsifiable
concentrate
22.5000
to
48.0000%
Flowable
concentrate
43.0000
to
43.4000%
Granular
5.0000
to
7.0000%
Liquid
ready
to
use
39.7000%
Pelleted/
tableted
5.0000%
Wettable
powder
50.0000
to
85.0000%
Methods
and
Rates
of
Application:
Types
of
Treatment:
Animal
bedding/
litter
treatment;
Animal
treatment
(spray);
Bait
application;
Band
treatment;
Bark
treatment;
Basal
spray
treatment;
Broadcast;
Chemigation;
Dip
treatment;
Directed
spray;
Drench;
Ground
spray;
High
volume
spray
(dilute);
Indoor
general
surface
treatment;
Low
volume
spray
(concentrate);
Mound
drench;
Mound
treatment;
Perimeter
treatment;
Premise
treatment;
Soil
drench
treatment;
Soil
incorporated
treatment
by
irrigation;
Soil
treatment;
Soil/
media
treatment;
Spray;
Surface
treatment;
Trunk
drench;
Ultra
low
volume
Equipment:
Airblast;
Aircraft;
Band
sprayer;
Chest
mounted
equipment;
Compressed
air
sprayer;
Dip
tank;
Drencher;
Electric
fogger;
Fogger;
Granule
applicator;
Ground;
Hand
held
duster;
Hand
held
sprayer;
High
pressure
sprayer;
High
volume
ground
sprayer;
Hose
end
sprayer;
Hydraulic
sprayer;
Knapsack
sprayer;
Low
pressure;
Low
pressure
ground
sprayer;
Low
volume
ground
sprayer;
Mechanical
sprayer;
Mist
blower;
Mist
sprayer;
Not
on
label;
Pail;
Power
sprayer;
Pressure
sprayer;
Sprayer;
Spreader;
Sprinklercan;
Sprinkler
irrigation;
Tank
Timing:
Bloom;
Boot;
Containerized;
Cool
weather
(65
80
F);
Delayed
dormant;
Dormant;
Foliar;
Fruit
thinning;
Heading;
Nonbearing;
Nurserystock;
Petal
fall;
Pink;
Plant
bed;
Popcorn;
Post
bloom;
Postharvest;
Prebloom;
Preharvest;
Preplant;
Seed
bed;
Silk;
Tassel;
Transplant;
When
needed
Use
Practice
Limitations:
(that
apply
to
all
uses
on
all
products)
Appendix
B:
Carbaryl
Occupational
Handler
Exposure
Data
Appendix
B/
Table
1:
Field
Recovery
Results
For
MRID
44658401
(Commercial
Pet
Groomers
During
Application
of
Adams
Carbaryl
Shampoo
Matrix
Level
(concentration)
Recovery
Range
(%)
Recovery
Mean
(%)
Recovery
S.
D.
(%)
Coefficient
of
Variation
(%)
Facial
swabs
Low
(0.
10
µg/
ml)
97
110
106
5.2
4.
9
Medium
(0.
50
µg/
ml)
96
99
97
1.5
1.
5
High
(1.
0
µg/
ml)
93
98
95
1.7
1.
8
Hand
Washes
Low
(0.
10
µg/
ml)
100
113
106
5.6
5.
3
Medium
(0.
50
µg/
ml)
92
100
97
3.1
3.
2
High
(1.
0
µg/
ml)
91
104
98
5
5.
1
Whole
body
dosimeters
Low
(1.
0
µg/
ml)
85
100
91
5.8
6.
4
Medium
(5.
0
µg/
ml)
82
95
87
6.1
7
High
(10
µg/
ml)
81
89
83
5
6
Glass
fiber
filter/
support
pad
Low
(1.
0
µg/
ml)
83
100
92
7.4
8
Medium
(5.
0
µg/
ml)
68
89
80
8.4
11
High
(10
µg/
ml)
85
95
91
3.8
4.
2
Appendix
B/
Table
2:
Dermal
Exposures
from
Whole
Body
Dosimeter
Parts
(Adjusted
for
Field
Recovery
Results)
a
For
MRID
44658401
(Commercial
Pet
Groomers
During
Application
of
Adams
Carbaryl
Shampoo)
Replicate
Lower
Arm
(µg)
Upper
Arm
(µg)
Lower
Leg
(µg)
Front
Torso
(µg)
Rear
Torso
(µg)
Total
(mg)
1
7543
185
0.57
1941
1
9.
7
2
6341
157
4
389
3
6.
9
3
1382
232
0.57
43
0.57
1.4
4
2986
3.9
0.
57
65
0.
57
3.
1
5
5441
61
31
6.6
5.
9
5.5
6
1680
589
3
420
0.57
2.7
7
2457
99
1.03
38
0.57
2.6
8
2497
277
8
445
8.2
3.
2
9
1224
7.01
0.57
1.6
0.
57
1.
2
10
14947
30
1330
10
1.8
16.3
11
839
0.34
0.57
0.92
0.57
0.84
12
1730
2518
35
10
1281.6
5.
6
13
4611
12
5.4
1.
4
0.57
4.6
14
4757
29
3.4
166
2.2
5
15
1180
162
15
30
10
1.4
16
763
0.23
0.57
3.9
0.
57
0.
77
Average
3774
260
90
223
82
4.4
Geometric
Mean
2647
35
3.7
30
2
3.1
Median
2477
46
3.2
34
0.
8
3.1
a
Field
recovery
for
100%
cotton
union
suits
averaged
87%.
The
values
in
this
table
represent
the
values
found
in
study
divided
by
0.87.
Example:
Replicate
1
Lower
arm;
6562µg
(actual)
÷
0.87
=
7543µg.
b
Total
(mg)
=(
Lower
Arm
+
Upper
Arm
+
Lower
Leg
+
Front
Torso
+
Back
Torso)
*
1mg/
1000µg.
Appendix
B/
Table
3:
Unit
Exposures
For
MRID
44658401
(Commercial
Pet
Groomers
During
Application
of
Adams
Carbaryl
Shampoo
)
Replicate
No.
ai
used
(mg)
Whole
Body
Dosimeter
(mg)
Hand
Rinses
(mg)
Head
Exposure
(mg)
Total
Dermal
Exposure
(mg)
Inhalation
Exposure
(µg)
mg
ai/
lb
ai
handled
mg
ai/
hr
application
mg
ai/
lb
dog
dermal
inhalation
dermal
inhalation
dermal
inhalation
1
2290
9.76
0.294
0.00897
10.1
1.
96
1994
0.389
3.493
0.00068
0.207
4.04
x
10
5
2
684
6.918
0.175
0.00533
7.1
0.
05
4714
0.006
2.752
0
0.
623
7.63
x
10
7
3
916
1.462
0.134
0.0007
1.6
0.
86
793
0.426
0.521
0.00028
0.0382
2.05
x
10
5
4
2004
3.056
0.248
0.00631
3.31
0.57
750
0.129
1.335
0.00023
0.184
3.17
x
10
5
5
1640
6.367
0.124
0.00338
6.49
0.65
1795
0.18
2.107
0.00021
0.18
1.81
x
10
5
6
1204
2.711
0.164
0.00325
2.88
0.54
1086
0.204
0.906
0.00017
0.0847
1.59
x
10
5
7
659
2.603
0.082
0.0007
2.69
0.59
1852
0.406
0.918
0.0002
0.113
2.47
x
10
5
8
373
3.28
0.105
0.00208
3.39
0.41
4123
0.499
1.246
0.00015
0.105
1.27
x
10
5
9
600
1.233
0.062
0.0003
1.3
0.
05
984
0.007
0.323
0
0.
0556
3.72
x
10
7
10
1747
16.544
0.466
0.012
17
1.4
4423
0.364
4.387
0.00036
0.379
3.12
x
10
5
11
945
0.841
0.292
0.00163
1.14
0.22
548
0.106
0.36
0.0001
0.0268
5.16
x
10
6
12
3715
15.329
0.145
0.00806
15.5
0.
97
1889
0.118
3.822
0.00024
0.325
2.04
x
10
5
13
1132
4.762
0.119
0.01177
4.89
1.18
1962
0.473
0.994
0.00024
0.173
4.17
x
10
5
14
1148
4.961
0.141
0.00429
5.11
0.05
2020
0.003
1.481
0
0.
312
5.31
x
10
7
15
706
1.459
0.239
0.00254
1.7
0.
76
1093
0.489
0.561
0.00025
0.096
4.29
x
10
5
16
1929
0.768
0.107
0.00111
0.88
0.48
207
0.113
0.293
0.00016
0.0362
1.98
x
10
5
Average
1356
5.1
0.
18
4.
5
5.3
0.
67
1900
0.24
1.6
0.
0002
0.18
2.0
x
10
5
Geometric
Mean
1148
3.4
0.
16
2.
9
3.6
0.
43
1800
0.12
1.1
0.
00096
0.13
1.1
x
10
5
Median
1140
3.2
0.
14
3.
3
3.4
0.
58
1800
0.19
1.1
0.
00021
0.14
2.0
x
10
5
Appendix
C:
Carbaryl
Occupational
Handler
Risk
Assessment
Appendix
C/
Table
1:
Sources
of
Exposure
Data
Used
In
The
Occupational
Carbaryl
Handler
Exposure
And
Risk
Calculations
Exposure
Scenario
(Number)
Data
Source
Standard
Assumptions
(8
hr
work
day)
Comments
Mixer/
Loader
Descriptors
Mixing/
Loading
Dry
Flowable
Formulations
(1a
through
1f)
PHED
V1.
1
(May
1997
Surrogate
Table)
350
and
1200
acres
for
aerial
applications
(7500
for
wide
area
uses),
40
acres
for
airblast,
80
and
200
acres
for
groundboom
in
agriculture
and
40
acres
on
turf,
5
acres
for
handguns
on
turf,
and
1000
gallons
for
handgun
applications
Baseline:
Hand,
inhalation,
and
dermal
data
=
acceptable
grades.
Hands
=
7
replicates;
Dermal
=
16
to
26
replicates;
and
Inhalation
=
23
replicates.
Low
confidence
in
hand/
dermal
data
because
of
number
of
hand
replicates.
Inhalation
data
are
high
confidence.
No
protection
factor
was
needed
to
define
the
unit
exposure
value.
PPE:
As
appropriate,
the
same
dermal
and
inhalation
data
were
used
as
for
the
baseline
coupled
with
a
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Hands
=
acceptable
grades.
Hands
=
21
replicates.
High
confidence
in
all
dermal
data.
Engineering
Controls:
A
protection
factor
of
98%
was
used
to
calculate
exposures
using
the
baseline
exposure
data.
Water
soluble
packet
data
(Scenario
4)
could
also
be
used
to
address
this
scenario.
A
protection
factor
has
been
used
but
the
WSP
rate/
acre
inputs
are
the
same
as
for
DF
formulations
(
refer
to
Scenario
4).
Loading
Granular
Formulations
(2a/
2b)
PHED
V1.
1
(May
1997
Surrogate
Table)
350
and
1200
acres
for
aerial
applications,
80
acres
for
agriculture
and
40
acres
on
turf
Baseline:
Hands
=
all
grades;
dermal
=
ABC
grade;
inhalation
=
acceptable
grade.
Hands
=
10
replicates;
Dermal
=
33
to
78
replicates;
and
inhalation
=
58
replicates.
Low
confidence
in
hand/
dermal
data
because
of
number
of
hand
replicates
and
quality.
Inhalation
data
are
high
confidence.
No
protection
factor
was
needed
to
define
the
unit
exposure
value.
PPE:
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Hands
=
acceptable
grades.
Hands
=
45
replicates.
High
confidence
in
hand
data.
Dermal
w/
coveralls
=
ABC
grade.
Dermal
w/
coveralls
=
12
to
59
replicates.
Low
confidence
in
dermal
data
because
of
low
number
of
replicates
and
grades.
Engineering
Controls:
A
98
percent
protection
factor
was
applied
to
the
baseline
data
to
account
for
the
use
of
an
engineering
control
(e.
g.,
closed
loading
system).
Mixing/
Loading
Liquid
Formulations
(3a
through
3f)
PHED
V1.
1
(May
1997
Surrogate
Table)
350
and
1200
acres
for
aerial
applications
(7500
for
wide
area
uses),
40
acres
for
airblast,
80
and
200
acres
for
groundboom
in
agriculture
and
40
acres
on
turf,
5
acres
for
handguns
on
turf,
and
1000
gallons
for
handgun
applications
Baseline:
Hands,
dermal,
and
inhalation
=
acceptable
grades.
Hands
=
53
replicates;
Dermal
=
72
to
122
replicates;
and
Inhalation
=
85
replicates.
High
confidence
in
hand,
dermal,
and
inhalation
data.
No
protection
factor
was
needed
to
define
the
unit
exposures.
PPE:
The
same
dermal
data
are
used
as
for
baseline
coupled
with
a
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
Hands
=
acceptable
grades.
Hands
=
59
replicates.
High
confidence
in
hand
data.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
Hands,
dermal,
and
inhalation
=
acceptable
grades.
Hands
=
31
replicates;
Dermal
=
16
to
22
replicates;
and
Inhalation
=
27
replicates.
High
confidence
in
hand,
dermal,
and
inhalation
data.
Gloves
were
used
coupled
with
engineering
controls
since
empirical
data
without
gloves
were
not
available
and
back
calculation
of
gloves
to
a
no
glove
scenario
is
believed
to
give
erroneously
high
estimates.
Gloves
are
also
required
by
WPS
based
on
acute
toxicity
concerns.
Appendix
C/
Table
1:
Sources
of
Exposure
Data
Used
In
The
Occupational
Carbaryl
Handler
Exposure
And
Risk
Calculations
Exposure
Scenario
(Number)
Data
Source
Standard
Assumptions
(8
hr
work
day)
Comments
Mixing/
Loading
Wettable
Powder
Formulations
(4a
through
4f)
PHED
V1.
1
(May
1997
Surrogate
Table)
350
and
1200
acres
for
aerial
applications
(7500
for
wide
area
uses),
40
acres
for
airblast,
80
and
200
acres
for
groundboom
in
agriculture
and
40
acres
on
turf,
5
acres
for
handguns
on
turf,
and
1000
gallons
for
handgun
applications
Baseline:
Hands,
dermal,
and
inhalation
=
ABC
grades.
Hands
=
7
replicates;
Dermal
=
22
to
45
replicates,
and
Inhalation
=
44
replicates.
Low
confidence
in
the
dermal/
hands
data
due
to
the
low
number
of
hand
replicates.
Medium
confidence
in
inhalation
data.
No
protection
factor
was
needed
to
define
the
unit
exposure
value.
PPE:
The
same
dermal
data
are
used
as
for
baseline
coupled
with
a
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
Hands
=
ABC
grades.
Hands
=
24
replicates.
Medium
confidence
in
hand
data.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
Dermal
=
AB
grade.
Hand
and
inhalation
=
all
grade.
Hands
=
9
replicates;
dermal
=
6
to
15
replicates;
and
inhalation
=
15
replicates.
Low
confidence
in
the
hand,
dermal,
and
inhalation
data.
No
protection
factor
was
needed
to
define
the
unit
exposure
value.
Engineering
controls
are
water
soluble
packets.
Gloves
were
used
coupled
with
engineering
controls
since
empirical
data
were
available
and
risk
estimates
for
some
scenarios
need
gloves
to
attain
risk
targets.
Gloves
are
also
required
by
WPS
based
on
acute
toxicity
concerns
Applicator
Descriptors
Applying
Sprays
with
a
Fixed
wing
Aircraft
(5a)
PHED
V1.
1
(May
1997
Surrogate
Table)
350
acres
and
1,200
acres
for
agriculture
and
7500
acres
for
wide
area
uses
Engineering
Controls:
Hands
=
acceptable
grade,
dermal
and
inhalation
=
ABC
grade.
Hands=
34
replicates,
dermal
=
24
to
48
replicates,
and
inhalation
=
23
replicates.
Medium
confidence
in
dermal
and
inhalation
data.
High
confidence
in
hand
data.
No
protection
factor
was
needed
to
define
the
unit
exposure
value.
Engineering
controls
are
the
only
plausible
exposure
scenario
for
this
application
method
as
open
cab
aircraft
are
not
available
and
not
considered
a
viable
application
tool.
Protective
gloves
not
used.
Applying
Sprays
with
a
Fixed
wing
Aircraft
(5b)
PHED
V1.
1
(May
1997
Surrogate
Table)
350
acres
and
1,200
acres
for
agriculture
Engineering
Controls:
Hands
and
inhalation
=
all
grade,
dermal
=
C
grade.
Hands=
4
replicates,
dermal
=
0
to
13
replicates,
and
inhalation
=
13
replicates.
Low
confidence
in
all
data.
No
protection
factor
was
needed
to
define
the
unit
exposure
value.
Engineering
controls
are
the
only
plausible
exposure
scenario
for
this
application
method
as
open
cab
aircraft
are
not
available
and
not
considered
a
viable
application
tool.
Protective
gloves
not
used.
Applying
Sprays
with
an
Airblast
Sprayer
(6)
PHED
V1.
1
(May
1997
Surrogate
Table)
40
acres
Baseline:
Dermal,
hand,
and
inhalation
=
acceptable
grades.
Hands
=
22
replicates,
dermal
=
32
to
49
replicates,
and
inhalation
=
47
replicates.
High
confidence
in
all
data.
No
protection
factor
was
needed
to
define
the
unit
exposure
value.
PPE:
The
same
dermal
data
are
used
as
for
baseline
coupled
with
a
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
Hands
=
acceptable
grades.
Hands
=
18
replicates.
High
confidence
in
hand
data.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
Hands
and
dermal
=
acceptable
grade,
and
inhalation
=
ABC
grade.
Hands=
20
replicates;
dermal
=
20
to
30
replicates;
and
inhalation
=
9
replicates.
High
confidence
in
hand
and
dermal
data.
Low
confidence
for
inhalation
data.
Gloves
were
used
coupled
with
engineering
controls
since
empirical
data
without
gloves
were
not
available
and
back
calculation
of
gloves
to
a
no
glove
scenario
is
believed
to
give
erroneously
high
(130
:
g/
lb
ai)
estimates
for
a
closed
cab
scenarios.
Appendix
C/
Table
1:
Sources
of
Exposure
Data
Used
In
The
Occupational
Carbaryl
Handler
Exposure
And
Risk
Calculations
Exposure
Scenario
(Number)
Data
Source
Standard
Assumptions
(8
hr
work
day)
Comments
Applying
Sprays
with
a
Groundboom
Sprayer
(7)
PHED
V1.
1
(May
1997
Surrogate
Table)
80
and
200
acres
for
groundboom
in
agriculture
and
40
acres
on
turf
Baseline:
Hand,
dermal,
and
inhalation
=
acceptable
grades.
Hands
=29
replicates,
dermal
=
23
to
42
replicates,
and
inhalation
=
22
replicates.
High
confidence
in
hand,
dermal,
and
inhalation
data.
No
protection
factors
were
needed
to
define
the
unit
exposure
values.
PPE:
The
same
dermal
data
are
used
as
for
baseline
coupled
with
a
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
Hands
=
ABC
grades.
Hands
=
21
replicates.
Medium
confidence
in
hand
data.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
Hand
and
dermal
=
ABC
grade.
Inhalation
=
acceptable
grades.
Hands
=
16
replicates;
dermal
=
20
to
31
replicates;
and
inhalation
=
16
replicates.
Medium
confidence
in
the
hand
and
dermal
data.
High
confidence
in
inhalation
data.
No
protection
factor
needed
to
define
the
unit
exposure
value.
Protective
gloves
not
used.
Applying
Granulars
with
a
Tractor
Drawn
Spreader
(8)
PHED
V1.
1
(May
1997
Surrogate
Table)
80
and
200
acres
for
groundboom
in
agriculture
and
40
acres
on
turf
Baseline:
Hand,
dermal,
and
inhalation
=
acceptable
grades.
Hands
=5
replicates,
dermal
=
1
to
5
replicates,
and
inhalation
=
5
replicates.
Low
confidence
in
hand,
dermal,
and
inhalation
data.
No
protection
factors
were
required
to
define
the
unit
exposure
values.
PPE:
As
appropriate,
the
same
dermal,
hand,
and
inhalation
data
are
used
as
for
the
baseline
coupled
with
a
50%
protection
factor
to
account
for
an
additional
layer
of
clothing,
a
90%
protection
factor
to
account
for
the
use
of
chemical
resistant
gloves.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
Hand,
inhalation,
and
dermal
=
acceptable
grades.
Hands
=
17
replicates;
dermal
=
27
to
30
replicates;
and
inhalation
=
37
replicates.
High
confidence
in
all
data.
No
protection
factor
needed
to
define
the
unit
exposure
value.
Protective
gloves
not
used.
Applying
with
Aerosol
Cans
(9)
PHED
V1.
1
(May
1997
Surrogate
Table)
2
cans
Baseline:
Hand,
dermal,
and
inhalation
=
acceptable
grades.
Hands
=
15
replicates;
dermal
=
15
replicates;
and
inhalation
=
15
replicates.
High
confidence
in
all
data.
No
protection
factor
was
needed
to
define
the
unit
exposure
values.
PPE:
The
same
dermal
data
are
used
as
for
baseline
coupled
with
a
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
Hands
=
acceptable
grades.
Hands
=
15
replicates.
High
confidence
in
hand
data.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
Not
considered
feasible
for
this
exposure
scenario.
Appendix
C/
Table
1:
Sources
of
Exposure
Data
Used
In
The
Occupational
Carbaryl
Handler
Exposure
And
Risk
Calculations
Exposure
Scenario
(Number)
Data
Source
Standard
Assumptions
(8
hr
work
day)
Comments
Applying
with
Trigger
Pump
Sprayer
(10)
MRID
410547
01
1
bottle
Single
Layer
Clothing
&
Glove
Scenario
Monitored
In
Study:
Hand,
dermal,
and
inhalation
=
acceptable
grades.
Hands
=
15
replicates;
dermal
=
15
replicates;
and
inhalation
=
15
replicates.
High
confidence
in
all
data.
No
protection
factor
was
needed
to
define
the
unit
exposure
values.
Engineering
Controls:
Not
considered
feasible
for
this
exposure
scenario.
There
are
no
data
compensation
issues
associated
with
this
study
as
there
is
a
signed
PHED
data
waiver.
Applying
with
a
Right
of
Way
Sprayer
(11)
PHED
V1.
1
(May
1997
Surrogate
Table)
1,000
gallons
Baseline:
Hand
and
inhalation
=
acceptable
grades.
Dermal
=
ABC
grades.
Hands
=
16
replicates;
dermal
=
4
to
20
replicates;
and
inhalation
=
16
replicates.
Low
confidence
in
hand
and
dermal
data
due
to
low
number
of
replicates.
High
confidence
in
inhalation
data.
No
protection
factor
was
needed
to
define
the
unit
exposure
values.
PPE:
The
same
dermal
data
are
used
as
for
baseline
coupled
with
a
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
Hands
=
acceptable
grades.
Hands
=
4
replicates.
Low
confidence
in
hand
data.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
Not
considered
feasible
for
this
exposure
scenario.
Applying
with
a
High
Pressure
Handwand
(12)
PHED
V1.
1
(May
1997
Surrogate
Table)
1,000
gallons
Baseline:
Hand,
dermal,
and
inhalation
=
all
grades.
Hands
=
2
replicates;
dermal
=
9
to
11
replicates;
and
inhalation
=
11
replicates.
Low
confidence
in
hand,
dermal,
and
inhalation
data.
No
protection
factor
was
needed
to
define
the
unit
exposure
values.
PPE:
The
same
dermal
data
are
used
as
for
baseline
coupled
with
a
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
Hands
=
all
grades.
Hands
=
9
replicates.
Low
confidence
in
hand
data.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
Not
considered
feasible
for
this
exposure
scenario.
Dog
Grooming
With
Shampoo
(13)
MRID
446584
01
½
of
6
oz
bottle
Clothing
(short
sleeved
tee
shirt,
smock
&
long
pants)
&
No
Gloves
Scenario
Monitored
In
Study:
Hand,
dermal,
and
inhalation
=
acceptable
grades.
Hands
=
16
replicates;
dermal
=
16
replicates;
and
inhalation
=
16
replicates.
High
confidence
in
all
data.
No
protection
factor
was
needed
to
define
the
unit
exposure
values.
Engineering
Controls:
Not
considered
feasible
for
this
exposure
scenario.
There
are
no
data
compensation
issues
associated
with
this
study
as
it
was
sponsored
by
Aventis
using
Carbaryl.
Appendix
C/
Table
1:
Sources
of
Exposure
Data
Used
In
The
Occupational
Carbaryl
Handler
Exposure
And
Risk
Calculations
Exposure
Scenario
(Number)
Data
Source
Standard
Assumptions
(8
hr
work
day)
Comments
Dusting
an
Animal
(14)
SOPs
for
Residential
Exposure
Assessments
(7/
97)
½
of
4
lb
bottle
per
SOPs
The
SOPs
For
Residential
Exposure
Assessment
served
as
the
basis
for
this
assessment
(i.
e.,
the
assumptions
that
were
used
to
predict
exposures
from
pet
use
products
in
which
a
percentage
of
the
application
rate
is
the
predictor
of
potential
dermal
dose).
The
scenario
is
based
on
the
use
of
a
baseline
clothing
scenario.
Calculations
in
which
additional
PPE
are
applied
are
not
appropriate
given
the
basis
for
the
assessment.
Additionally,
the
use
of
engineering
controls
are
not
considered
feasible
for
this
exposure
scenario.
Dispersing
Granulars
&
Baits
By
Hand
(15)
PHED
V1.
1
(May
1997
Surrogate
Table)
1
acre
Baseline:
Values
not
included
because
barehanded
data
were
not
available
and
hand
exposures
are
key
to
this
scenario.
PPE:
Dermal,
hand,
and
inhalation
=
ABC
grades.
Hands
=
15
replicates,
dermal
=
16
replicates,
and
inhalation
=
16
replicates.
Medium
confidence
in
all
data.
The
same
dermal
data
are
used
as
for
baseline
coupled
with
a
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
Not
considered
feasible
for
this
exposure
scenario.
Dispersing
Granulars
&
Baits
With
a
Spoon
(16)
MRID
452507
01
1
acre
Baseline:
Values
not
included
because
barehanded
data
were
not
available
and
hand
exposures
are
key
to
this
scenario.
PPE:
Dermal,
hand,
and
inhalation
=
acceptable
grades.
Hands
=
10
replicates,
dermal
=
10
replicates,
and
inhalation
=
10
replicates.
Low
confidence
in
all
data
because
dernal
dosimeters
were
unprotected
and
the
number
of
replicates.
Protective
gloves
were
worn.
A
50%
protection
factor
to
account
for
a
layer
of
clothing
was
used.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
Not
considered
feasible
for
this
exposure
scenario.
There
are
no
data
compensation
issues
associated
with
this
study
as
it
was
sponsored
by
Aventis.
Appendix
C/
Table
1:
Sources
of
Exposure
Data
Used
In
The
Occupational
Carbaryl
Handler
Exposure
And
Risk
Calculations
Exposure
Scenario
(Number)
Data
Source
Standard
Assumptions
(8
hr
work
day)
Comments
Mixer/
Loader/
Applicator
Descriptors
Mixing/
Loading/
Applying
Liquid
Sprays
w/
Low
Pressure,
High
Volume
Turfgun
(17)
MRID
449722
01
5
acres
Baseline:
Values
back
calculated
using
90%
protection
factor
for
gloves.
Non
hand
dermal
data
for
single
layer
monitored
(see
PPE).
PPE:
See
EPA
review
for
data
quality
(Bangs,
2001),
data
are
considered
high
quality.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
A
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
Study
monitored
single
layer
clothing
with
gloves.
Engineering
Controls:
Not
considered
feasible
for
this
exposure
scenario.
There
are
no
data
compensation
issues
associated
with
this
study
as
it
was
sponsored
by
ORETF
(Aventis
is
a
member).
Turfgun,
no
glove
data
were
not
back
calculated
using
a
90
percent
protection
factor
as
it
is
deemed
unreliable.
WP
formulation
in
WSP
packaging
used
for
turfgun
assessment
as
the
unit
exposures
for
this
scenario
were
slightly
higher
than
for
the
other
scenarios
and
deemed
representative
of
current
products/
packaging.
Mixing/
Loading/
Applying
Wettable
Powders
with
a
Low
Pressure
Sprayer
(18a)
PHED
V1.
1
(May
1997
Surrogate
Table)
40
gallons
for
ornamentals
and
20,000ft2
for
poultry
houses
Baseline:
The
only
empirical
data
that
are
available
are
based
on
the
use
of
chemical
resistant
gloves.
It
is
not
appropriate
to
back
calculate
a
non
glove
hand
exposure
level
for
this
scenario
as
it
is
considered
an
overestimate
of
exposure
because
the
hands
are
a
key
contributor
to
exposure.
PPE:
Dermal
and
inhalation=
ABC
grades;
and
hands
=
acceptable
grades.
Dermal
=
16
replicates;
hands
=
15
replicates;
and
inhalation
=
16
replicates.
Medium
confidence
in
inhalation,
dermal,
and
hand
data.
A
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
Not
considered
feasible
for
this
exposure
scenario.
Mixing/
Loading/
Applying
Liquids
with
a
Low
Pressure
Sprayer
(18b)
PHED
V1.
1
(May
1997
Surrogate
Table)
40
gallons
for
ornamentals
and
20,000ft2
for
poultry
houses
Baseline:
Hands
=
all
grades;
dermal
and
inhalation
=
ABC
grades.
Dermal
=
9
to
80
replicates;
hands
=
70
replicates;
and
inhalation
=
80
replicates.
Medium
confidence
in
inhalation
data.
Low
confidence
in
dermal
and
hand
data.
No
protection
factor
was
needed
to
define
the
unit
exposure
values.
PPE:
The
same
dermal
data
are
used
as
for
baseline
coupled
with
a
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
Hand
=
10
replicates.
Hands=
ABC
grades
Low
confidence
in
hand
data.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
Not
considered
feasible
for
this
exposure
scenario.
Appendix
C/
Table
1:
Sources
of
Exposure
Data
Used
In
The
Occupational
Carbaryl
Handler
Exposure
And
Risk
Calculations
Exposure
Scenario
(Number)
Data
Source
Standard
Assumptions
(8
hr
work
day)
Comments
Mixing/
Loading/
Applying
with
a
Backpack
Sprayer
(19)
PHED
V1.
1
(May
1997
Surrogate
Table)
40
gallons
for
ornamentals
and
20,000ft2
for
poultry
houses
Baseline:
Dermal
and
inhalation
=
acceptable
grades.
Dermal
=
9
to
11
replicates
and
inhalation
=
11
replicates.
Low
confidence
in
dermal
and
inhalation
data.
The
only
empirical
data
that
are
available
are
based
on
the
use
of
chemical
resistant
gloves.
It
is
generally
not
appropriate
to
back
calculate
a
non
glove
hand
exposure
levels,
an
extrapolation
has
been
completed
for
this
scenario,
however,
because
the
empirical
data
indicate
that
hands
are
a
minor
contributor
to
overall
exposure
levels.
PPE:
Hands
=
C
grades.
Hands
=
11
replicates.
Low
confidence
in
hand
data.
The
same
dermal
data
are
used
as
for
baseline
coupled
with
a
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
Not
considered
feasible
for
this
exposure
scenario.
Loading/
Applying
Granulars
with
a
Belly
Grinder
(20)
PHED
V1.
1
(May
1997
Surrogate
Table)
1
acre
Baseline:
Inhalation
=
acceptable
grades;
dermal
and
hands
=
ABC
grades.
Dermal
=
29
to
45
replicates;
hands
=
23
replicates;
and
inhalation
=
40
replicates.
High
confidence
in
inhalation
data.
Medium
confidence
in
dermal
and
hand
data.
No
protection
factor
was
needed
to
define
the
unit
exposure
values.
PPE:
The
same
dermal
data
are
used
as
for
baseline
coupled
with
a
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
Hands
=
all
grades.
Hands
=
20
replicates.
Low
confidence
in
hand
data.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
Not
considered
feasible
for
this
exposure
scenario.
Loading/
Applying
granulars
with
a
push
spreader
(21)
PHED
V1.
1
(May
1997
Surrogate
Table)
5
acres
Baseline:
Values
back
calculated
using
90%
protection
factor
for
gloves.
Non
hand
dermal
data
for
single
layer
monitored
(see
PPE).
PPE:
See
EPA
review
for
data
quality
(Bangs,
2001),
data
are
considered
high
quality.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
A
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
Study
monitored
single
layer
clothing
with
gloves.
Engineering
Controls:
Not
considered
feasible
for
this
exposure
scenario.
There
are
no
data
compensation
issues
associated
with
this
study
as
it
was
sponsored
by
ORETF
(Aventis
is
a
member).
Mixing/
Loading/
Applying
with
a
Handheld
Fogger
(22)
No
Data
No
Data
No
Data
Appendix
C/
Table
1:
Sources
of
Exposure
Data
Used
In
The
Occupational
Carbaryl
Handler
Exposure
And
Risk
Calculations
Exposure
Scenario
(Number)
Data
Source
Standard
Assumptions
(8
hr
work
day)
Comments
Mixing/
Loading/
Applying
with
a
Handheld
Fogger
(23)
No
Data
No
Data
No
Data
Mixing/
Loading/
Applying
with
a
Granular
Backpack
Applicator
(24)
MRID
451672
01
1
acre
Clothing
(coverall
and
apron
worn
on
back)
&
Gloves
Scenario
Monitored
In
Study:
High
confidence
in
all
data.
No
protection
factor
was
needed
to
define
the
unit
exposure
values.
Engineering
Controls:
Not
considered
feasible
for
this
exposure
scenario.
There
are
no
data
compensation
issues
associated
with
this
study
as
it
was
sponsored
by
Aventis
using
Carbaryl.
Mixing/
Loading/
Applying
with
a
Tree
Injector
(25)
No
Data
No
Data
No
Data
Drench/
Dipping
Forestry
&
Ornamentals
(26)
PHED
V1.
1
(May
1997
Surrogate
Table)
100
gallons
of
solution
prepared
Addresses
only
solution
preparation
aspects
of
process.
This
has
been
addressed
using
open
mixing
liquid
data
presented
above
in
Scenario
3.
Engineering
controls
are
not
appropriate
for
this
scenario.
Mixing/
Loading/
Applying
with
a
Sprinkler
Can
(27)
PHED
V1.
1
(May
1997
Surrogate
Table)
10
gallons
Scenario
assessed
using
hose
end
sprayer
data
which
are
believed
to
result
in
similar
exposures.
However,
the
extrapolation
should
be
considered
rangefinder
in
nature.
Baseline:
Inhalation
=
ABC
grades;
dermal
=
C
grade;
and
hands
=
E
grade.
Dermal
=
8
replicates;
hands
=
8
replicates;
and
inhalation
=
8
replicates.
Low
confidence
in
all
data.
Study
monitored
total
deposition.
A
50%
protection
factor
to
account
for
single
layer
of
clothing
was
used
to
define
the
unit
exposure
values.
PPE:
The
same
dermal
data
are
used
as
for
baseline
coupled
with
a
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
A
90
%
protection
factor
was
used
to
account
for
the
use
of
protective
gloves.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
Not
considered
feasible
for
this
exposure
scenario.
Appendix
C/
Table
1:
Sources
of
Exposure
Data
Used
In
The
Occupational
Carbaryl
Handler
Exposure
And
Risk
Calculations
Exposure
Scenario
(Number)
Data
Source
Standard
Assumptions
(8
hr
work
day)
Comments
Flagger
Descriptors
Flagging
Aerial
Spray
Applications
(28a)
PHED
V1.
1
(May
1997
Surrogate
Table)
350
acres
and
1,200
acres
Baseline:
Hands,
dermal,
and
inhalation
=
acceptable
grades.
Dermal
=
18
to
28
replicates;
hands
=
30
replicates;
and
inhalation
=
28
replicates.
High
confidence
in
dermal,
hand,
and
inhalation
data.
No
protection
factor
was
required
to
calculate
unit
exposures.
PPE:
The
same
dermal
data
are
used
as
for
baseline
coupled
with
a
50%
protection
factor
to
account
for
an
additional
layer
of
clothing.
Hand
=
acceptable
grades.
Hands=
6
replicates.
Low
confidence
in
hand
data.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
The
same
data
are
used
as
for
baseline
coupled
with
a
98%
protection
factor
to
account
for
the
use
of
an
engineering
control
(e.
g.,
sitting
in
a
vehicle).
Flagging
Aerial
Spray
Applications
(28b)
PHED
V1.
1
(May
1997
Surrogate
Table)
350
acres
and
1,200
acres
Baseline:
Hands
and
inhalation
=
All
grades.
Dermal
=
ABC
grades.
Dermal
=
16
to
20
replicates;
hands
=
4
replicates;
and
inhalation
=
4
replicates.
Low
confidence
in
all
data.
Study
monitored
total
deposition.
A
50%
protection
factor
to
account
for
single
layer
of
clothing
was
used
to
define
the
unit
exposure
values.
PPE:
The
same
dermal
data
are
used
as
for
baseline
coupled
with
a
50%
protection
factor
to
account
for
an
additional
layer
of
clothing
and
a
90%
protection
factor
to
account
for
the
use
of
gloves.
Respirator
protection
factors
of
either
5
or
10
applied
to
account
for
the
use
of
either
dust/
mist
masks
or
cannister
type
devices
(e.
g.,
organic
vapor
removing
half
face
device).
Engineering
Controls:
The
same
data
are
used
as
for
baseline
coupled
with
a
98%
protection
factor
to
account
for
the
use
of
an
engineering
control
(e.
g.,
sitting
in
a
vehicle).
C
All
Standard
Assumptions
are
based
on
an
8
hour
work
day
as
estimated
by
the
Agency.
C
All
handler
exposure
assessments
in
this
document
are
based
on
the
"Best
Available"
data
as
defined
by
the
PHED
SOP
for
meeting
Subdivision
U
Guidelines
(i.
e.,
completing
exposure
assessments).
Best
available
grades
are
assigned
to
data
as
follows:
matrices
with
A
and
B
grade
data
(i.
e.,
Acceptable
Grade
Data)
and
a
minimum
of
15
replicates;
if
not
available,
then
grades
A,
B
and
C
data
and
a
minimum
of
15
replicates;
if
not
available,
then
all
data
regardless
of
the
quality
(i.
e.,
All
Grade
Data)
and
number
of
replicates.
High
quality
data
with
a
protection
factor
take
precedence
over
low
quality
data
with
no
protection
factor.
Generic
data
confidence
categories
are
assigned
as
follows:
High
=
grades
A
and
B
and
15
or
more
replicates
per
body
part
Medium
=
grades
A,
B,
and
C
and
15
or
more
replicates
per
body
part
Low
=
grades
A,
B,
C,
D
and
E
or
any
combination
of
grades
with
less
than
15
replicates.
C
PHED
grading
criteria
do
not
reflect
overall
quality
of
the
reliability
of
the
assessment.
Sources
of
the
exposure
factors
should
also
be
considered
in
the
risk
management
decision.
Appendix
D:
Carbaryl
Residue
Dissipation
(DFR
&
TTR)
Data
Appendix
E:
Carbaryl
Occupational
Postapplication
Risk
Assessment
Appendix
F:
Carbaryl
Residential
Handler
Exposure
Data
Appendix
F/
Table
1:
Exposure
Data
From
MRID
444399
01
(Carbaryl
Applicator
Exposure
Study
During
Application
of
Sevin
®
5
Dust
to
Dogs
By
the
Non
Professional)
Replicate
lb
ai
used
Inner
(µg)
Outer
(µg)
Hand
(µg)
Face/
Neck
(µg)
Total
Dermal
Exposure
a
(mg)
Inhalation
Exposure
(µg)
Upper
Arm
Front
Torso
Back
Torso
Upper
Leg
Lower
Arm
Lower
Leg
1
0.
0034
40.7
217
122
70.7
8810
13100
5770
98.1
28
383
2
0.
016
173
445
230
130
28300
37000
12500
215
79
232
3
0.
0079
21.8
77.7
60.9
56.4
4240
1630
3890
43.5
10
252
4
0.
0042
23.3
43.9
50.9
40.8
4110
13800
5380
26.8
23
244
5
0.
0083
37.6
216
108
64.3
26200
24200
8140
180
59
149
6
0.
0025
16.4
25
38.3
9.
06
2470
541
4940
23.3
8.
1
37.4
7
0.
003
11.7
97.3
99.3
31.4
3150
2570
4490
61.6
11
66.3
8
0.
0068
41.9
111
89.5
21.8
6450
380
10500
43.4
18
170
9
0.
0068
27.2
79.4
215
31.7
3400
345
11600
65.4
16
158
10
0.012
145
648
224
278
67900
11500
11900
263
93
525
11
0.0047
20
79.4
78.1
53.2
12800
581
7300
280
21
244
12
0.022
97.4
454
435
232
44100
8310
24600
73.5
78
486
13
0.0093
50.5
85.6
64.5
42.3
7680
577
4350
31
13
173
14
0.0014
5.03
17.2
16.7
4.
92
1710
133
3870
11.9
5.
8
82.5
15
0.0085
14.8
159
129
18.6
6320
1350
5980
74
14
216
16
0.014
61.7
138
138
40.3
22000
1960
5140
41
30
509
17
0.0069
15.5
110
53
20
15600
1060
4570
33.1
21
209
18
0.0064
16.3
102
91.8
61.7
13500
651
6830
104
21
67.4
19
0.006
5.12
33.2
39.7
13.8
3830
271
9080
20.3
13
37.1
20
0.004
47.3
66.1
121
127
2720
1990
7650
41.8
13
170
Appendix
F/
Table
2:
Exposure
Data
For
Hose
End
Sprayers
From
MRID
444598
01
(Mixer
Loader
Applicator
Exposure
to
RP
2
Liquid
(21%).
Carbaryl
Mixer/
Loader/
Applicator
Exposure
Study
during
Application
of
RP
2
Liquid
(21%)
Sevin
®
Ready
to
Use
Insect
Spray
or
Sevin
®
10
Dust
to
Home
Garden
Vegetables)
Rep
Carbaryl
Applied
(lb)
Inner
Dosimeter
(µg)
Outer
Dosimeter
Lower
Arm
(µg)
Outer
Dosimeter
Lower
leg
(µg)
Hand
(µg)
Face/
Neck
Wipe
(µg)
Total
Dermal
Exposure
a
(µg)
Inhalation
Exposrue
(µg)
1
0.
11
19.1
71.3
571
2770
0.5
3.
43
0.
24
2
0.
076
3.0
7.
26
2548
1030
0.5
3.
59
0.
07
3
0.
045
8.8
34.1
624
291
0.5
0.
96
0.
07
4
0.
025
10.3
10.9
337
1560
0.5
1.
92
0.
07
5
0.
05
3.
0
1.97
1776
1100
17
2.90
0.07
6
0.
083
15.3
32.9
4080
2170
0.5
6.
30
0.
25
7
0.
047
3.0
3.
01
710
462
0.5
1.
18
0.
15
8
0.
052
9.8
62.5
937
618
0.5
1.
63
0.
23
9
0.
041
4.4
26
320
437
0.5
0.
79
0.
07
10
0.053
6.6
32.2
194
691
0.5
0.
92
0.
07
11
0.07
3.0
0.
5
2008
331
0.5
2.
34
0.
07
12
0.051
183.3
61.9
673
3380
0.5
4.
30
0.
21
13
0.031
3.0
7
28.6
693
0.5
0.
73
0.
07
14
0.075
3.0
44
465
3700
0.5
4.
21
0.
07
15
0.026
6.4
3.
4
130
62.6
0.
5
0.20
0.07
16
0.036
30.7
48.8
2587
4440
58
7.16
0.16
17
0.051
85.1
3037
1969
3240
0.5
8.
33
0.
07
18
0.095
3.0
23.3
422
612
0.5
1.
06
0.
07
19
0.052
10.1
158
537
385
0.5
1.
09
0.
23
20
0.025
3.0
0.
5
22.8
149
0.5
0.
18
0.
07
Appendix
F/
Table
3:
Exposure
Data
For
Low
Pressure
Handwand
Sprayers
From
MRID
444598
01
(Mixer
Loader
Applicator
Exposure
to
RP
2
Liquid
(21%).
Carbaryl
Mixer/
Loader/
Applicator
Exposure
Study
during
Application
of
RP
2
Liquid
(21%)
Sevin
®
Ready
to
Use
Insect
Spray
or
Sevin
®
10
Dust
to
Home
Garden
Vegetables)
Rep
Carbaryl
Applied
(lb)
Inner
Dosimeter
(µg)
Outer
Dosimeter
Lower
Arm
(µg)
Outer
Dosimeter
Lowel
leg
(µg)
Hand
(µg)
Face/
Neck
Wipe
(µg)
Total
Dermal
Exposure
a
(mg)
1
0.
02
3.
0
20.6
921.0
215.0
0.
5
1.16
2
0.
02
3.
0
15.8
476.0
381.0
0.
5
0.88
3
0.
02
3.
0
14.3
76.7
208.0
0.
5
0.30
4
0.
02
30.0
214.0
485.0
2100.0
9.
8
2.84
5
0.
01
3.
0
2.5
36.8
168.0
0.
5
0.21
6
0.
02
7.
9
84.4
3449.0
165.0
0.
5
3.71
7
0.
02
5.
2
7.7
85.3
235.0
0.
5
0.33
8
0.
02
18.6
41.4
876.0
205.0
0.
5
1.14
9
0.
02
3.
0
9.7
99.4
203.0
0.
5
0.32
10
0.02
10.0
5.
9
259.0
378.0
0.
5
0.65
11
0.02
3.0
2.
1
157.0
50.6
0.
5
0.21
12
0.01
3.0
69.4
64.6
451.0
0.
5
0.59
13
0.02
3.0
9.
9
247.0
1550.0
0.
5
1.81
14
0.02
3.0
5.
4
242.0
219.0
0.
5
0.47
15
0.02
7.9
3.
5
2278.0
100.0
0.
5
2.39
16
0.02
5.6
28.3
245.0
415.0
0.
5
0.69
17
0.02
4.5
0.
5
245.0
203.0
0.
5
0.45
18
0.02
3.0
2.
6
299.0
188.0
0.
5
0.49
19
0.02
16.4
5.
5
47.5
86.3
0.
5
0.16
20
0.02
17.5
328.0
255.0
118.0
0.
5
0.72
Appendix
F/
Table
4:
Exposure
Data
For
Ready
to
use
Sprayers
From
MRID
444598
01
(Mixer
Loader
Applicator
Exposure
to
RP
2
Liquid
(21%).
Carbaryl
Mixer/
Loader/
Applicator
Exposure
Study
during
Application
of
RP
2
Liquid
(21%)
Sevin
®
Ready
to
Use
Insect
Spray
or
Sevin
®
10
Dust
to
Home
Garden
Vegetables)
Rep
Carbaryl
Applied
(lb)
Inner
Dosimeter
(µg)
Outer
Dosimeter
Lower
Arm
(µg)
Outer
Dosimeter
Lowel
leg
(µg)
Hand
(µg)
Face/
Neck
Wipe
(µg)
Total
Dermal
Exposure
a
(mg)
Inhalation
Exposure
(µg)
1
0.
0024
3.0
7.
43
21.6
270
0.5
0.
31
0.
66
2
0.
0022
5.5
10.5
33.7
81.9
0.
5
0.13
0.56
3
0.
0028
7.2
10.2
26.1
654
0.5
0.
70
0.
29
4
0.
0025
6.4
13.3
82.9
225
0.5
0.
33
0.
42
5
0.
002
3.0
8.
43
80.8
197
0.5
0.
29
0.
36
6
0.
0022
3.0
7.
92
41.1
150
0.5
0.
20
0.
07
7
0.
002
4.9
5.
5
22
301
0.5
0.
33
0.
36
8
0.
0022
4.3
6.
65
40.4
115
0.5
0.
17
0.
44
9
0.
0021
3.0
0.
5
1.72
44.5
0.
5
0.05
0.07
10
0.0022
3.0
0.
5
2.46
98.1
0.
5
0.11
0.07
11
0.0021
3.0
0.
5
2.3
45.1
0.
5
0.05
0.07
12
0.0022
10.0
2.
29
7.
22
198
0.5
0.
22
0.
19
13
0.0022
3.0
5.
41
3.
51
44.8
0.
5
0.05
0.07
14
0.0021
7.2
2.
46
18.4
16.5
0.
5
0.05
0.23
15
0.002
3.0
3.
84
4.
48
28.2
0.
5
0.04
0.07
16
0.0022
61.8
5.
12
6.
33
392
11.9
0.
48
0.
07
17
0.0022
5.2
2.
23
12.2
3.
67
0.
5
0.02
0.07
18
0.0022
3.0
0.
5
2.54
34.8
0.
5
0.04
0.07
19
0.0022
3.0
4.
39
17.2
67.2
0.
5
0.09
0.07
20
0.0022
3.0
2.
79
18
23.7
0.
5
0.05
0.07
Appendix
F/
Table
5:
Exposure
Data
For
Dust
Applications
From
MRID
444598
01
(Mixer
Loader
Applicator
Exposure
to
RP
2
Liquid
(21%).
Carbaryl
Mixer/
Loader/
Applicator
Exposure
Study
during
Application
of
RP
2
Liquid
(21%)
Sevin
®
Ready
to
Use
Insect
Spray
or
Sevin
®
10
Dust
to
Home
Garden
Vegetables)
Rep
Carbaryl
Applied
(lb)
Inner
Dosimeter
(µg)
Outer
Dosimeter
Lower
Arm
(µg)
Outer
Dosimeter
Lowel
leg
(µg)
Hand
(µg)
Face/
Neck
Wipe
(µg)
Total
Dermal
Exposure
a
(mg)
Inhalation
Exposure
(µg)
1
0.
0033
126.9
296
902
884
3.23
2.22
7.5
2
0.
025
98.9
346
932
13300
23.5
14.70
15.1
3
0.
0072
57.1
112
1281
526
12.5
1.
99
9.
93
4
0.
012
96.5
453
243
719
34.4
1.
55
26.8
5
0.
012
150.0
139
282
1530
5.85
2.11
3.57
6
0.
013
38.4
309
381
488
3.62
1.22
7.94
7
0.
0045
50.4
359
83
568
3.97
1.06
21.9
8
0.
0093
26.0
1815
59.8
228
5.53
2.13
0.07
9
0.
013
86.5
230
95.4
667
15.9
1.
10
27.4
10
0.015
25.0
452
127
413
13.3
1.
03
5.
73
11
0.019
53.1
167
306
1020
7.25
1.55
40.7
12
0.012
21.6
90.9
66.9
2920
1.96
3.10
7.89
13
0.029
77.7
381
587
423
8.95
1.48
57.7
14
0.0026
44.1
227
305
3030
2.35
3.61
37.1
15
0.02
71.4
153
219
351
1.21
0.80
2.51
16
0.0086
165.7
174
624
1440
1.88
2.41
9.34
17
0.03
93.4
275
413
494
6.89
1.28
42.1
18
0.044
82.2
282
949
259
12.7
1.
59
24.9
19
0.013
171.1
1022
133
1500
23.7
2.
85
29.7
20
0.026
36.0
221
65.5
1210
2.52
1.54
6.74
Appendix
F/
Table
6:
Exposure
Data
For
Hose
End
Sprayers
From
MRID
445185
01
(Carbaryl
Mixer/
Loader/
Applicator
Exposure
Study
during
Application
of
RP
2
Liquid
(21%)
to
Fruit
Trees
and
Ornamental
Plants)
Rep
Carbaryl
Applied
(lb)
Inner
Dosimeter
(µg)
Outer
Dosimeter
Lower
Arm
(µg)
Outer
Dosimeter
Lowel
leg
(µg)
Hand
(µg)
Face/
Neck
Wipe
(µg)
Total
Dermal
Exposure
a
(mg)
Inhalation
Exposure
(µg)
1
0.
026
4.5
15
37
128
0.5
0.
19
0.
07
2
0.
02
3.
8
133
1890
227
0.5
2.
45
0.
07
3
0.
066
17.0
995
2218
5480
3.6
8.
71
0.
07
4
0.
053
26.5
193
1230
13200
2.2
14.65
0.15
5
0.
026
3.7
337
348
952
0.5
1.
64
0.
29
6
0.
026
18.5
49
161
82
0.5
0.
31
0.
07
7
0.
02
3.
0
99
220
1060
0.5
1.
38
0.
07
8
0.
022
3.6
78
213
694
0.5
0.
99
0.
07
9
0.
021
4.6
28
87
779
0.5
0.
90
0.
07
10
0.02
4.3
298
226
460
1.9
0.
99
0.
07
11
0.035
10.4
47
119
248
0.5
0.
43
0.
08
12
0.046
5.1
23
72
130
0.5
0.
23
0.
07
13
0.042
3.0
270
181
2060
0.5
2.
52
0.
07
14
0.09
9.1
567
1824
1400
0.5
3.
80
0.
23
15
0.029
3.0
123
193
428
0.5
0.
75
0.
07
16
0.026
11.3
36
181
2850
0.5
3.
08
0.
07
17
0.062
3.0
75
878
643
0.5
1.
60
0.
07
18
0.024
21.5
251
97
1830
0.5
2.
20
0.
07
19
0.073
3.0
180
301
736
0.5
1.
22
0.
07
20
0.024
3.9
9.
4
124
521
0.5
0.
66
0.
07
Appendix
F/
Table
7:
Exposure
Data
For
Low
Pressure
Handwand
Sprayers
From
MRID
445185
01
(Carbaryl
Mixer/
Loader/
Applicator
Exposure
Study
during
Application
of
RP
2
Liquid
(21%)
to
Fruit
Trees
and
Ornamental
Plants)
Rep
Carbaryl
Applied
(lb)
Inner
Dosimeter
(µg)
Outer
Dosimeter
Lower
Arm
(µg)
Outer
Dosimeter
Lowel
leg
(µg)
Hand
(µg)
Face/
Neck
Wipe
(µg)
Total
Dermal
Exposure
a
(mg)
Inhalation
Exposure
(µg)
1
0.
018
3.0
5.
6
11
432
0.5
0.
45
0.
07
2
0.
015
6.7
55
467
259
0.5
0.
78
0.
07
3
0.
02
34.0
571
491
1450
20
2.57
0.07
4
0.
019
4.9
34
88
381
0.5
0.
51
0.
07
5
0.
013
5.5
133
1297
3080
0.5
4.
52
0.
07
6
0.
014
8.4
56
147
567
0.5
0.
78
0.
07
7
0.
018
7.5
906
378
825
0.5
2.
12
0.
07
8
0.
02
12.1
95
440
2970
1.2
3.
52
0.
32
9
0.
017
15.2
27
182
524
0.5
0.
75
0.
16
10
0.015
5.0
42
146
414
1.3
0.
61
0.
24
11
0.019
25.2
59
303
493
0.5
0.
88
0.
07
12
0.018
3.0
15
108
139
0.5
0.
27
0.
07
13
0.018
9.0
79
281
271
0.5
0.
64
0.
07
14
0.02
9.5
209
522
917
0.5
1.
66
0.
07
15
0.015
11.4
131
780
247
1.8
1.
17
0.
37
16
0.017
9.2
25
437
864
0.5
1.
33
0.
2
17
0.02
3.0
78
639
198
0.5
0.
92
0.
07
18
0.017
3.0
51
285
267
0.5
0.
61
0.
38
19
0.02
6.9
41
81
373
0.5
0.
50
0.
07
20
0.018
8.9
81
605
436
1.4
1.
13
0.
33
Appendix
G:
Carbaryl
Residential
Handler
Risk
Assessment
Appendix
G/
Table
1:
Residential
Handler
Scenario
Descriptions
for
the
Use
of
Carbaryl
Exposure
Scenario
(Number)
Data
Source
Standard
Assumptions
(8
hr
work
day)
Comments
a
Mixer/
Loader/
Applicator
Descriptors
Garden:
Ready
to
use
trigger
sprayer
(1)
MRID
444598
01
1/
4
to
1
bottle
(1
bottle
is
SOP
requirement,
others
shown
for
characterization)
A
total
of
40
replicates
were
monitored
in
this
study.
Half
of
the
people
wore
gloves
and
the
other
half
did
not.
The
clothing
scenario
represents
short
sleeved
shirt,
short
pants,
and
no
gloves.
The
data
are
considered
high
quality
by
the
Agency.
There
are
no
data
compensation
issues
associated
with
this
study
as
it
was
sponsored
by
Aventis
Garden:
Ornamental
Duster
(2)
MRID
444598
01
1/
4
to
1
bottle
(1
bottle
is
SOP
requirement,
others
shown
for
characterization)
A
total
of
20
replicates
were
monitored
in
this
study.
No
individuals
wore
gloves.
The
clothing
scenario
represents
short
sleeved
shirt,
short
pants,
and
no
gloves.
The
data
are
considered
high
quality
by
the
Agency.
There
are
no
data
compensation
issues
associated
with
this
study
as
it
was
sponsored
by
Aventis
Garden:
Hose
end
Sprayer
(3)
MRID
444598
01
1000
ft
2
or
100
gallons
output
(1000ft
2
is
SOP
requirement,
others
shown
for
characterization)
A
total
of
40
replicates
were
monitored
in
this
study.
Half
of
the
people
wore
gloves
and
the
other
half
did
not.
The
clothing
scenario
represents
short
sleeved
shirt,
short
pants,
and
no
gloves.
The
data
are
considered
high
quality
by
the
Agency.
There
are
no
data
compensation
issues
associated
with
this
study
as
it
was
sponsored
by
Aventis
Garden:
Low
Pressure
Handwand
Sprayer
(4)
MRID
444598
01
5
gallons
or
1000
ft
2
(5
gallons
is
SOP
requirement,
others
shown
for
characterization)
A
total
of
40
replicates
were
monitored
in
this
study.
Half
of
the
people
wore
gloves
and
the
other
half
did
not.
The
clothing
scenario
represents
short
sleeved
shirt,
short
pants,
and
no
gloves.
The
data
are
considered
high
quality
by
the
Agency.
There
are
no
data
compensation
issues
associated
with
this
study
as
it
was
sponsored
by
Aventis
Trees
and
Ornamentals:
Low
Pressure
Handwand
Sprayer
(5)
MRID
445185
01
5
gallons
or
1000
ft
2
(5
gallons
is
SOP
requirement,
others
shown
for
characterization)
A
total
of
20
replicates
were
monitored
in
this
study.
No
individuals
wore
gloves.
The
clothing
scenario
represents
short
sleeved
shirt,
short
pants,
and
no
gloves.
The
data
are
considered
high
quality
by
the
Agency.
There
are
no
data
compensation
issues
associated
with
this
study
as
it
was
sponsored
by
Aventis
Trees
and
Ornamentals:
Hose
end
Sprayer
(6)
MRID
445185
01
100
gallons
or
1000
ft
2
(1000
ft
2
is
SOP
requirement,
others
shown
for
characterization)
A
total
of
20
replicates
were
monitored
in
this
study.
No
individuals
wore
gloves.
The
clothing
scenario
represents
short
sleeved
shirt,
short
pants,
and
no
gloves.
The
data
are
considered
high
quality
by
the
Agency.
There
are
no
data
compensation
issues
associated
with
this
study
as
it
was
sponsored
by
Aventis
Mixing/
Loading/
Applying
with
a
Backpack
Sprayer
(7)
PHED
V1.
1
(7/
97
Residential
SOP
Surrogate
Table)
5
gallons
or
1000
ft
2
(5
gallons
is
SOP
requirement,
others
shown
for
characterization)
Inhalation
and
dermal
=
acceptable
grades.
Hand
data
=
C
grade.
Dermal
=
9
to
11
replicates,
hand
=
11
replicates,
and
inhalation
=
11
replicates.
Low
confidence
in
data.
Hand
exposure
values
were
back
calculated
using
empirical
data
that
were
generated
using
chemical
resistant
gloves
and
a
90
percent
protection
factor.
An
additional
10x
safety
factor
was
applied
to
the
hand
exposure
value
because
the
calculated
hand
exposure
value
did
not
correspond
to
the
level
expected
given
the
other
dermal
exposure
values
for
the
scenario
(the
10x
factor
addition
was
completed
based
on
instructions
contained
in
the
Residential
SOPs).
Appendix
G/
Table
1:
Residential
Handler
Scenario
Descriptions
for
the
Use
of
Carbaryl
Exposure
Scenario
(Number)
Data
Source
Standard
Assumptions
(8
hr
work
day)
Comments
a
Lawncare:
Hose
end
Sprayer
(8)
MRID
44972201
1000
ft
2
for
spot
treatments
and
20,000ft
2
for
broadcast
applications
A
total
of
60
replicates
were
monitored
in
this
study.
Half
of
the
subjects
used
ready
to
use
packaging
while
the
others
used
open
pour.
The
values
used
for
assessment
were
open
pour.
The
clothing
scenario
represents
short
sleeved
shirt,
short
pants,
and
no
gloves.
The
data
are
considered
high
quality
by
the
Agency.
There
are
no
data
compensation
issues
associated
with
this
study
as
it
was
sponsored
by
Aventis
Dusting
a
Dog
(9)
MRID
444399
01
½
bottle
of
product
A
total
of
40
replicates
were
monitored
in
this
study.
Half
of
the
people
wore
gloves
and
the
other
half
did
not.
The
clothing
scenario
represents
short
sleeved
shirt,
short
pants,
and
no
gloves.
The
data
are
considered
high
quality
by
the
Agency.
There
are
no
data
compensation
issues
associated
with
this
study
as
it
was
sponsored
by
Aventis
Dipping
a
Dog
(10)
SOPs
for
Residential
Exposure
Assessments
(7/
97)
½
bottle
of
product
The
SOPs
For
Residential
Exposure
Assessment
served
as
the
basis
for
this
assessment
(i.
e.,
the
assumptions
that
were
used
to
predict
exposures
from
pet
use
products
in
which
a
percentage
of
the
application
rate
is
the
predictor
of
potential
dermal
dose).
The
scenario
is
based
on
the
use
of
a
residential
clothing
scenario
(i.
e.,
short
pants,
short
sleeved
shirt,
no
gloves,
no
respirator).
Note
that
the
same
value
is
used
as
for
the
occupational
handler
scenarios.
The
refinement
of
the
SOPs
for
Residential
Exposure
Assessment
is
such
that
furhter
delineation
based
on
clothing
scenario
is
not
appropriate
(i.
e.,
to
alter
value
based
on
use
of
short
vs.
long
pants
and
long
sleeved
vs.
short
sleeved
shirts).
Lawncare:
Granular
and
Baits
By
Bellygrinder
(11)
SOPs
for
Residential
Exposure
Assessments
(7/
97)
1000
ft
2
for
spot
treatment
Inhalation
=
acceptable
grades.
Hand
and
dermal
data
=
ABC
grade.
Dermal
=
20
to
45
replicates,
hand
=
23
replicates,
and
inhalation
=
40
replicates.
Medium
confidence
in
dermal
and
hand
data.
High
confidence
in
inhalation
data.
Lawncare:
Granular
and
Baits
By
Push
type
Spreader
(12)
MRID
44972201
20,000ft
2
for
broadcast
applications
A
total
of
30
replicates
were
monitored
in
this
study.
The
clothing
scenario
represents
short
sleeved
shirt,
short
pants,
and
no
gloves.
The
data
are
considered
high
quality
by
the
Agency.
There
are
no
data
compensation
issues
associated
with
this
study
as
it
was
sponsored
by
Aventis
Lawncare:
Granular
and
Baits
By
Hand
(13)
SOPs
for
Residential
Exposure
Assessments
(7/
97)
1000
ft
2
for
spot
treatment
Dermal,
hand
and
inhalation
data
=
ABC
grade.
Dermal
=
16
replicates,
hand
=
16
replicates,
and
inhalation
=
16
replicates.
Medium
confidence
in
all
data.
Aerosol
Can
(14)
SOPs
for
Residential
Exposure
Assessments
(7/
97)
1
can
Hand
data
=
acceptable
grades.
Dermal
and
inhalation
data
=
ABC
grade.
Dermal
=
30
replicates,
hand
=
15
replicates,
and
inhalation
=
30
replicates.
Medium
confidence
in
all
data.
Appendix
G/
Table
1:
Residential
Handler
Scenario
Descriptions
for
the
Use
of
Carbaryl
Exposure
Scenario
(Number)
Data
Source
Standard
Assumptions
(8
hr
work
day)
Comments
a
Flea
Collar
(15)
SOPs
for
Residential
Exposure
Assessments
(7/
97)
1
collar
The
SOPs
For
Residential
Exposure
Assessment
served
as
the
basis
for
this
assessment
(i.
e.,
the
assumptions
that
were
used
to
predict
exposures
from
pet
use
products
in
which
a
percentage
of
the
application
rate
is
the
predictor
of
potential
dermal
dose).
The
scenario
is
based
on
the
use
of
a
residential
clothing
scenario
(i.
e.,
short
pants,
short
sleeved
shirt,
no
gloves,
no
respirator).
Note
that
the
same
value
is
used
as
for
the
occupational
handler
scenarios.
The
refinement
of
the
SOPs
for
Residential
Exposure
Assessment
is
such
that
furhter
delineation
based
on
clothing
scenario
is
not
appropriate
(i.
e.,
to
alter
value
based
on
use
of
short
vs.
long
pants
and
long
sleeved
vs.
short
sleeved
shirts).
Sprinkler
Can
(16)
MRID
445185
01
5
gallons
Data
from
hose
end
sprayer
applications
to
trees
and
ornamentals
was
used
to
assess
this
scenario.
The
results
should
be
considered
as
rangefinder
in
nature
to
account
for
the
extrapolation
completed
for
this
assessment.
Ornamental
Paint
On
(17)
SOPs
for
Residential
Exposure
Assessments
(7/
97)
1
gallon
Hand
data
=
acceptable
grade.
Dermal
and
inhalation
data
=
C
grade.
Dermal
=
14
to
15
replicates,
hand
=
15
replicates,
and
inhalation
=
15
replicates.
Low
to
medium
confidence
in
all
data.
a
All
Standard
Assumptions
are
based
on
an
8
hour
work
day
as
estimated
by
HED.
BEAD
data
were
not
available.
bAll
handler
exposure
assessments
in
this
document
are
based
on
the
"Best
Available"
data
as
defined
by
the
PHED
SOP
for
meeting
Subdivision
U
Guidelines
(i.
e.,
completing
exposure
assessments).
Best
available
grades
are
assigned
to
data
as
follows:
matrices
with
A
and
B
grade
data
(i.
e.,
Acceptable
Grade
Data)
and
a
minimum
of
15
replicates;
if
not
available,
then
grades
A,
B
and
C
data
and
a
minimum
of
15
replicates;
if
not
available,
then
all
data
regardless
of
the
quality
(i.
e.,
All
Grade
Data)
and
number
of
replicates.
High
quality
data
with
a
protection
factor
take
precedence
over
low
quality
data
with
no
protection
factor.
Generic
data
confidence
categories
are
assigned
as
follows:
High
=
grades
A
and
B
and
15
or
more
replicates
per
body
part
Medium
=
grades
A,
B,
and
C
and
15
or
more
replicates
per
body
part
Low
=
grades
A,
B,
C,
D
and
E
or
any
combination
of
grades
with
less
than
15
replicates.
c
PHED
grading
criteria
do
not
reflect
overall
quality
of
the
reliability
of
the
assessment.
Sources
of
the
exposure
factors
should
also
be
considered
in
the
risk
management
decision.
Appendix
H:
Carbaryl
Residential
Postapplication
Risk
Assessment
For
Turf
Uses
Appendix
I:
Carbaryl
Residential
Postapplication
Risk
Assessment
For
Garden/
Ornamental
Uses
Appendix
J:
Carbaryl
Residential
Postapplication
Risk
Assessment
For
Pet
Uses
Appendix
K:
Determination
of
Deposition
Factors
For
Carbaryl
Mosquito
Control
Uses
Background
Information:
Carbaryl
has
been
historically
used
for
the
control
of
insect
pests
such
as
mosquitoes
and
black
flies
in
a
manner
that
has
employed
the
use
of
Ultra
low
Volume
(ULV)
application
methods
over
wide
areas.
As
the
reregistration
process
has
progressed,
the
labels
for
these
types
of
applications
have
been
reviewed
and
the
Aventis
Corporation
has
submitted
a
draft
label
for
the
Sevin
XLR
(4
lb
ai/
gallon)
product
which
has
been
used
to
develop
the
risk
assessment
for
these
uses.
Aventis
is
interested
in
maintaining
this
use
pattern
even
though
the
marketshare
for
carbaryl
in
this
area
has
declined
in
recent
years
due
to
the
use
of
the
synthetic
pyrethroids
and
other
chemistries.
According
to
the
Sevin
XLR
label,
applications
can
be
made
using
ground,
aerial
or
handheld
equipment
suitable
for
fogging
urban
environments
(e.
g.,
backpack
or
handheld
foggers).
ULV
type
applications
or
thermal
fogging
applications
are
allowable
based
on
the
label.
The
label
indicates
that
the
optimal
droplet
size
is
8
to
30
µm
by
mass
median
diameter
(MMD)
or
volume
median
diameter
(VMD)
calculations
for
ground
fogger
applications.
For
aerial
applications,
the
droplet
spectra
that
is
specified
has
a
calculated
VMD
of
less
than
50
µm
and
no
more
than
5
percent
of
the
droplets
should
be
larger
than
80
µm.
The
label
presents
a
range
of
application
rates
from
0.016
to
1.0
lb
ai/
acre
(i.
e.,
0.016,
0.15,
and
1.0
lb
ai/
acre).
These
use
rates
have
not
been
linked
to
specific
pests
or
pest
pressures
on
the
label.
Applications
can
be
made
using
undiluted
material
or
with
a
1:
1
or
1:
2
dilution
rate.
Agricultural
Engineering
Considerations:
With
few
notable
exceptions
such
as
public
health
scenarios
(e.
g.,
mosquito
control),
the
general
intent
during
most
pesticide
applications
is
to
confine
the
deposition
of
applied
chemicals
to
specific
target
areas
such
as
agricultural
fields.
Economic
concerns,
health
concerns,
environmental
concerns,
and
efficacy
are
the
generally
recognized
rationale
for
limiting
off
target
deposition.
Pesticide
applicators
can
control
deposition
patterns
through
the
use
of
specific
types
of
equipment
and
by
controlling
application
parameters.
Several
application
parameters
can
potentially
impact
deposition
patterns
of
liquid
form
pesticides
in
the
environment
during
application
(e.
g.,
nozzle
size,
application
pressure,
vehicle
configuration
and
speed,
meteorological
conditions
including
environmental
stability,
and
physical
chemical
characteristics
of
the
formulation).
As
indicated
above,
ULV
mosquito
control
applications
serve
as
the
basis
for
this
assessment.
The
general
intent
of
these
types
of
applications
is
antithetical
to
most
pesticide
applications
in
that
spray
drift
is
generally
not
inhibited
but
promoted
in
order
to
broaden
the
effective
treatment
area
and
ensure
that
the
resulting
droplets
stay
aloft
for
as
long
as
possible.
In
fact,
the
efficacy
of
mosquito
adulticide
compounds
is
based
on
droplets
contacting
in
flight
mosquitos.
As
a
result,
there
are
significant
agricultural
engineering
differences
that
were
considered
by
The
Agency
in
this
assessment.
These
include:
C
Release
heights
for
mosquito
control
aerial
ULV
applications
are
typically
100
to
500
feet
(or
even
higher)
as
opposed
to
most
typical
agricultural
aerial
applications
where
the
release
height
is
generally
as
low
as
the
pilot
can
go
(i.
e.,
often
10
feet
or
less).
Release
height
can
significantly
impact
spray
drift
(i.
e.,
the
higher
the
release,
the
longer
to
time
of
impact
with
target
area,
and
the
more
potential
for
drift).
A
release
height
of
300
feet
was
used
in
this
assessment
(i.
e.,
the
upper
limit
application
height
allowed
in
the
AgDRIFT
model).
C
Nozzle
configurations
are
such
that
extremely
small
droplets
are
released
as
opposed
to
typical
aerial
applications
(i.
e.,
Sevin
XLR
label
specifies
VM
of
50
µm
while
the
values
for
most
agricultural
applications
are
100
µm
or
more).
C
Larger
aircraft
are
generally
used
to
make
malaria
control
applications.
For
example,
Lee
County
Florida,
one
of
the
largest
Florida
mosquito
abatement
districts,
has
a
fleet
of
Douglas
DC3s
and
Huey
Helicopters.
The
DC3
is
a
much
larger
aircraft
than
the
common
agricultural
application
fixed
wing
aircraft
(e.
g.,
Air
Tractor
AT401).
These
differences
are
significant
when
predicting
deposition
and
were
addressed
in
the
Agency
calculation
of
deposition
after
an
aerial
ULV
application.
The
DC3
was
used
as
the
basis
for
all
AgDRIFT
calculations
completed
by
The
Agency.
Predictive
Tools
and
Data:
The
Agency
has
used
state
of
the
art
tools
in
order
to
calculate
deposition
rates
resulting
from
ground
based
and
aerial
ULV
applications
as
well
as
to
calculate
the
postapplication
dermal
exposures
that
result
from
entry
into
areas
previously
treated
with
carbaryl
using
these
techniques.
The
Agency
used
AgDrift
V2.01
to
predict
the
amount
of
residues
that
would
deposit
in
residential
areas
after
aerial
ULV
application,
published
data
were
used
to
predict
deposition
after
ground
ULV
applications,
and
the
latest
residential
exposure
assessment
methods
were
used
to
calculate
the
risks
associated
with
these
residues.
The
first
aspect
of
this
exposure/
risk
assessment
required
the
calculation
of
realistic
deposition
rates
from
the
aerial
and
ground
based
ULV
applications
of
carbaryl
(i.
e.,
addressed
in
this
appendix
residential
exposure
methods
are
discussed
in
detail
in
Section
3
of
the
document).
The
Agency
could
have
taken
a
very
simplistic
approach
of
assigning
the
application
rate
as
the
deposition
after
an
application.
However,
The
Agency
did
not
utilize
this
approach
given
the
current
state
of
knowledge
pertaining
to
spray
drift
and
recent
industry
and
agency
efforts
in
this
area
(i.
e.,
this
approach
would
generally
be
considered
as
unrealistic
given
the
intent
of
mosquito
control
applications).
There
are
a
number
of
predictive
tools
and
open
literature
articles
that
pertain
to
this
technical
area.
Given
that
ground
based
and
aerial
ULV
applications
are
allowable,
models
and
data
were
identified
to
support
a
human
health
exposure/
risk
assessment
for
each
scenario.
[Note:
The
Agency
recognizes
that
there
are
potential
issues
with
the
selection
and
use
of
these
models
in
this
assessment.
As
such,
the
use
of
each
model
for
completing
this
exposure/
risk
assessment
is
appropriately
characterized
(see
below).]
Aerial
ULV:
In
order
to
calculate
deposition
from
aerial
ULV
applications,
The
Agency
used
AgDRIFT
(V
2.01)
which
is
the
model
that
was
developed
as
a
result
of
the
efforts
of
the
Spray
Drift
Task
Force
(SDTF).
The
SDTF
is
a
coalition
of
pesticide
registrants
whose
primary
objectives
were
to
develop
a
comprehensive
database
of
off
target
drift
information
in
support
of
pesticide
registrations
and
an
appropriate
model
system.
This
model
was
selected
based
on
the
consensus
of
several
experts
in
the
spray
drift
area
because
it
represents
the
current
state
of
the
art.
The
Agency
discussed
the
issue
of
model
selection
with
several
experts
in
the
spray
drift
community
prior
to
selecting
AgDRIFT
(e.
g.,
Sandra
L.
Bird,
U.
S.
EPA;
Steven
G.
Perry,
U.
S.
EPA;
Milton
E.
Teske,
Continuum
Dynamics;
Pat
Skyler,
U.
S.
Forest
Service;
Arnet
Jones,
U.
S.
EPA;
and
Harold
Thistle,
U.
S.
Forest
Service).
The
Agency
considered
using
the
USDA
Forest
Service
Cramer
BarryGrim
Model
(commonly
referred
to
as
FSCBG).
FSCBG
was
developed
through
support
from
the
U.
S.
Forest
Service,
in
cooperation
with
the
U.
S.
Army,
and
has
been
in
existence
for
over
20
years
in
various
iterations.
Actual
support
and
development
of
FSCBG
was
completed
by
Continuum
Dynamics,
Inc.
located
in
Princeton,
New
Jersey
under
the
technical
direction
of
Milton
E.
Teske.
However,
it
was
decided
that
AgDRIFT
should
be
used
because
it
is
based
on
essentially
the
same
algorithms
as
FSCBG
(personal
communication
with
Milton
E.
Teske
of
Contiuum
Dynamics),
it
has
undergone
extensive
validation
by
the
SDTF,
and
it
is
very
user
friendly
compared
to
FSCBG.
AgDRIFT
is
a
Microsoft
Windows
based
personal
computer
program
that
is
provided
to
the
U.
S.
Environmental
Protection
Agency's
Office
of
Pesticide
Programs
as
a
product
of
the
Cooperative
Research
and
Development
Agreement
(CRADA)
between
EPA's
Office
of
Research
and
Development
and
the
SDTF.
AgDRIFT
predicts
the
motion
of
spray
material
released
from
aircraft,
including
the
mean
position
of
the
material
and
the
position
variance
about
the
mean
as
a
result
of
turbulent
fluctuations.
AgDRIFT
enhancements
include
a
significant
solution
speed
increase,
an
in
memory
computation
of
deposition
and
flux
as
the
solution
proceeds,
and
extensive
validation
based
on
180
separate
aerial
treatments
performed
during
field
trials
in
1992
and
1993
by
the
SDTF.
Ground
ULV:
In
contrast
to
the
aerial
ULV
scenario,
the
data
available
to
predict
deposition
patterns
and
resulting
exposures
from
ground
based
ULV
malaria
applications
are
limited.
In
fact,
The
Agency
utilized
two
published
journal
articles
and
a
preliminary
model
developed
for
the
Environmental
Fate
and
Effects
Division
of
OPP
by
EPA's
Office
of
Research
and
Development
as
the
basis
of
this
effort.
These
documents
include:
Mass
Recovery
of
Malathion
in
Simulated
Open
Field
Mosquito
Adulticide
Tests:
N.
S.
Tietze,
P.
G.
Hester,
and
K.
R.
Shaffer;
Archives
of
Environmental
Contamination
and
Toxicology;
26:
473
477
(1994).
[Note:
This
document
was
used
as
the
primary
source
of
deposition
rates
resulting
from
ground
based
ULV
mosquito
applications.]
Downwind
Drift
and
Deposition
of
Malathion
on
Human
Targets
From
Ground
Ultra
Low
Volume
Mosquito
Sprays:
J.
C.
Moore,
J.
C.
Dukes,
J.
R.
Clark,
J.
Malone,
C.
F.
Hallmon,
and
P.
G.
Hester;
Journal
of
the
American
Mosquito
Control
Association;
Vol.
9,
No.
2
(June,
1993).[
Note:
This
document
was
used
as
the
primary
source
of
deposition
rates
resulting
from
ground
based
ULV
mosquito
applications
and
as
a
confirmatory
source
of
exposure
data.]
Modeling
of
Deposition
From
Mosquito
Adulticide
Applications:
S.
G.
Perry
and
W.
B.
Petersen
of
EPA/
ORD
for
Arnet
Jones
of
EPA/
OPP
(February
7,
1995).
[Note:
This
is
an
internal
document
that
has
not
been
peer
reviewed.
It
was
used
only
for
confirmatory
purposes
in
this
exposure/
risk
assessment.]
Determination
of
Deposition
Rates:
Deposition
rates
were
determined
for
both
aerial
and
ground
based
ULV
application
methods
as
a
percentage
of
the
nominal
application
rate
(i.
e.,
how
much
of
the
target
application
rate
actually
deposited
on
outdoor
surfaces
such
as
turf).
The
application
rates
used
to
complete
the
assessment
are
the
range
specified
above.
As
indicated
above,
AgDRIFT
V
2.01
was
used
to
calculate
the
deposition
rate
from
aerial
ULV
applications.
The
following
inputs
were
used
as
the
basis
of
the
AgDRIFT
calculations:
C
AgDRIFT
Model
Tier:
3.
C
Droplet
Size
Distribution:
Dv0.1
=
25.59
µm;
Dv0.5
=
51.0
µm;
Dv0.9
=
74.27
µm;
and
<141
µm
=
100
percent
(developed
to
reflect
droplet
spectrum
requirements
of
Sevin
XLR
label).
[Note:
The
droplet
distribution
was
developed
based
on
the
Sevin
label.
No
proprietary
SDTF
data
were
used
in
the
completion
of
this
assessment.]
C
Spray
Material:
User
defined
option
(oil
option).
Inputs
include:
nonvolatile
rate
0.5
lb
per
acre,
specific
gravity
1.2
(calculated
based
on
approximately
10
pounds
per
gallon),
spray
rate
0.25
gallons/
acre,
active
ingredient
application
rate
(0.5
lb
ai/
acre),
and
evaporation
rate
(1
µm
2
/deg
C/
sec).
[Note:
Several
of
these
parameters
do
not
exactly
coincide
with
the
Sevin
XLR
label
but
were
used
because
the
Sevin
XLR
label
inputs
exceeded
the
allowable
input
parameters.
These
differences
are
not
expected
to
significantly
effect
the
AgDRIFT
results
because
a
nonvolatile
oil
was
selected,
hence
the
critical
input
is
the
active
ingredient
application
rate.
Additionally,
no
proprietary
SDTF
physical
property
data
were
used
in
the
completion
of
this
assessment.
]
C
Aircraft:
User
defined
option
(fixed
wing
option).
Inputs
include:
Douglas
DC3,
wingspan:
94.6
ft
(semispan
47.28
ft),
typical
application
airspeed:
228
mph,
weight:
21397
pounds,
planform
area:
999
ft
2
,
propeller
RPM:
2550,
propeller
radius:
5.81
feet,
engine
vertical
distance:
4.003
feet,
and
engine
forward
distance:
20.01
feet.
[Note:
DC3
specific
inputs
were
obtained
from
the
FSCBG
(V4)
aircraft
library.]
C
Nozzles:
User
defined
option.
Inputs
include
number
of
nozzles:
60,
vertical
distance
of
nozzles
from
wing:
2.66
feet,
horizontal
distance
from
wing:
0.82
feet,
and
horizontal
distance
limit:
75
percent.
C
Meteorology:
Inputs
were
not
changed
from
Tier
3
recommendations
of
wind
speed:
2
mph,
wind
direction:
90
degrees
(perpendicular
to
flight
path),
temperature:
86°
F,
and
relative
humidity:
50
percent.
C
Control:
Inputs
were
altered
from
the
Tier
3
recommendations.
The
parameters
that
were
used
included
a
spray
release
height
of
300
feet,
20
spray
lines
(aircraft
passes)
in
each
application
event,
a
swath
width
of
500
feet,
and
a
swath
displacement
based
on
the
aircraft
centerline.
C
Advanced
Settings:
Inputs
were
not
changed
from
Tier
3
recommendations
of
wind
speed
height
(2
meters),
maximum
compute
time
(600
seconds),
maximum
downwind
distance
(795
meters),
vortex
decay
rate
(0.56
m/
s),
aircraft
drag
coefficient
(0.1),
propeller
efficiency
(0.8),
and
ambient
pressure
(1013
mb).
AgDRIFT
is
capable
of
producing
a
variety
of
useful
outputs.
The
key
for
The
Agency
in
this
assessment
was
to
determine
from
the
model
what
percentage
of
the
application
volume
remained
aloft
and
what
percentage
of
the
resulting
droplets
deposited
on
the
surfaces
in
the
treatment
area
as
well
as
downwind
from
the
treatment
area.
AgDRIFT
is
generally
intended
to
calculate
deposition
rates
in
areas
that
are
downwind
from
the
treatment
area
(i.
e.,
presented
from
the
border
of
the
treatment
area
to
areas
of
interest
downwind).
The
Agency
has
used
the
values
at
the
border
of
the
treatment
area
to
represent
the
deposition
rate
within
the
treated
area.
It
is
clear
from
the
results
that
from
the
edge
of
the
treatment
area
to
2000
feet
downwind,
approximately
9.5
percent
of
the
theoretical
application
is
deposited.
This
value
is
intuitively
consistent
with
what
one
might
suspect
would
occur
considering
the
agricultural
engineering
parameters
associated
with
mosquito
applications
(see
graph
below).
As
indicated
above,
two
published
journal
articles
served
as
the
basis
for
predicting
deposition
rates,
as
a
percentage
of
the
application
rate,
after
ground
based
ULV
application
for
mosquito
control
(i.
e.,
Tietze,
et
al,
1994
and
Moore,
et
al,
1993).
Both
of
these
studies
were
completed
using
ULV
formulations
of
malathion
(91
and
95
percent).
The
Agency
anticipates
that
the
"behavior"
of
these
formulations
in
the
referenced
studies
would
not
be
significantly
different
from
the
Sevin
XLR
formulation
because
the
physical
chemical
properties
of
the
malathion
formulations
and
the
nature
of
the
application
would
be
expected
to
be
similar
(i.
e.,
the
Agency
believes
the
malathion
formulations
to
be
acceptable
surrogates
for
Baytex
in
this
analysis).
In
the
study
conducted
by
Moore,
et
al
both
human
exposure
and
deposition
was
quantified
over
5
separate
application
events.
A
91
percent
formulation
of
malathion
was
applied
in
April
and
May
of
1989
in
the
early
evening
(a
time
of
day
for
relative
atmospheric
stability).
A
Leco
HD
ULV
cold
aerosol
generator
(Lowndes
Engineering
Company,
Valdosta
Georgia)
was
used
to
make
each
application.
The
application
parameters
included
a
fluid
flow
rate
of
4.3
fluid
ounces
per
minute,
a
vehicle
groundspeed
of
10
mph,
and
a
nominal
application
rate
of
0.05
lb
ai/
acre
(i.
e.,
equates
to
a
deposition
rate
of
0.51
µg/
cm
2
).
Deposition
was
monitored
at
three
locations
downwind
from
the
treatment
area
(i.
e.,
15.2m,
30.4m,
and
91.2m).
For
the
events
considered
in
the
deposition
calculations,
"average
amounts
of
malathion
deposited
on
ground
level
at
15.2,
30.4,
and
91.2
m
were
not
significantly
different."
The
percentage
of
the
application
rate
reported
to
have
deposited
ranged
from
1
to
14
percent.
The
mean
deposition
value
for
all
measurements
was
4.3
percent
(n=
35,
CV=
98).
In
the
study
conducted
by
Tietze,
et
al
only
deposition
was
quantified
over
6
separate
application
events
(i.
e.,
one
event
was
not
included
in
deposition
calculations
"due
to
negative
air
stability").
The
application
parameters
were
similar
to
that
used
by
Moore
et
al.
A
95
percent
formulation
of
malathion
was
applied
from
May
to
August
of
1993.
A
Leco
1600
ULV
cold
aerosol
generator
(Lowndes
Engineering
Company,
Valdosta
Georgia)
was
also
used
to
make
each
application.
The
application
parameters
included
a
fluid
flow
rate
of
4.3
fluid
ounces
per
minute,
a
vehicle
groundspeed
of
10
mph,
and
a
nominal
application
rate
of
0.057
lb
ai/
acre
(i.
e.,
equates
to
a
deposition
rate
of
0.58
µg/
cm
2
).
Deposition
was
monitored
at
four
locations
downwind
from
the
treatment
area
(i.
e.,
5
m,
25
m,
100
m
and
500
m).
For
the
events
considered
in
the
deposition
calculations,
"malathion
mass
deposited
differed
significantly
between
the
500
m
site
and
the
three
closer
sites
(df
=
3;
F
value
=
3.42;
P<
0.05)."
The
percentage
of
the
application
rate
reported
to
have
deposited
(not
including
500
m
samples
which
were
much
less)
ranged
up
to
5.8
percent.
The
mean
deposition
value
for
all
measurements
was
3.8
percent.
Considering
the
data
that
are
available
in
the
Tietze
et
al
and
Moore
et
al
papers,
an
off
target
deposition
rate
of
5
percent
was
used
by
The
Agency
to
evaluate
ground
based
ULV
applications.
A
value
slightly
higher
than
the
mean
values
for
both
studies
was
selected
because
of
the
variability
in
the
data
and
the
limited
number
of
datapoints.
It
should
be
noted
that
this
value
is
also
consistent
with
the
draft
modeling
assessment
for
ground
ULV
approaches
completed
by
S.
T.
Perry
and
W.
B.
Petersen
of
EPA's
Office
of
Research
and
Development
(i.
e.,
within
a
factor
of
5).
Perry
and
Petersen
used
"the
INPUFF
Lagrangian
puff
model"
as
the
basis
for
their
assessment
(Petersen
and
Lavdas,
1986:
INPUFF
2.0
A
Multiple
Source
Gaussian
Puff
Dispersion
Algorithm,
User's
Guide,
EPA/
600/
8
86/
024).
Depending
on
the
scenario
selected
from
this
document,
deposition
rates
ranged
from
approximately
2.5
percent
deposition
450
m
downwind
to
15
to
20
percent
deposition
immediately
adjacent
to
the
treatment
zone.
The
following
deposition
rates
presented
as
a
percentage
of
the
application
rate
served
as
the
basis
of
the
postapplication
exposure
calculations
completed
by
The
Agency:
C
Ground
based
ULV
=
5
percent
of
application
rate,
and
C
Aerial
ULV
=
9.5
percent
of
application
rate.
Appendix
L:
Carbaryl
Residential
Postapplication
Risk
Assessment
For
Mosquito
Control
Appendix
M:
Carbaryl
Residential
Postapplication
Risk
Assessment
For
Oyster
Bed
Uses
| epa | 2024-06-07T20:31:42.166576 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0005/content.txt"
} |
EPA-HQ-OPP-2002-0138-0006 | Supporting & Related Material | "2002-07-31T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
May
30,
2002
MEMORANDUM
SUBJECT:
Carbaryl.
List
A
Reregistration
Case
0080.
Chemical
No.
056801.
Revised
Product
and
Residue
Chemistry
Chapters
for
the
Reregistration
Eligibility
Decision.
DP
Barcode:
D283328.
FROM:
Felecia
Fort,
Chemist
Reregistration
Branch
1
Health
Effects
Division
(7509C)
THRU:
Whang
Phang,
Ph.
D.,
Branch
Senior
Scientist
Reregistration
Branch
1
Health
Effects
Division
(7509C)
TO:
Jeff
Dawson,
Chemist
Health
Effects
Division(
7509C)
and
Anthony
Britten,
Chemical
Review
Manager
Special
Review
and
Reregistration
Division
(7508C)
Attached
are
the
Revised
Product
and
Residue
Chemistry
Chapters
for
the
Carbaryl
Reregistration
Eligibility
Decision
Document
(RED).
The
chapters
were
revised
to
incorporate
comments
submitted
by
the
registrant.
These
revisions
include
changes
to
the
requirements
for
label
amendments,
changes
to
label
acceptance
dates,
and
changes
to
the
food/
feed
use
patterns
table.
The
chapters
were
also
changed
to
reflect
uses
that
are
not
being
supported
by
the
registrant
or
have
been
cancelled.
Product
Chemistry
Most
pertinent
data
requirements
are
satisfied
for
the
Aventis
99%
T,
except
that
data
are
required
for
UV/
visible
absorption
(OPPTS
830.7050).
For
the
Aventis
97.5%
and
80%
FIs,
and
the
Drexel
50%
FI,
additional
data
are
required
concerning
product
identity
and
composition,
discussion
of
formation
of
impurities,
certified
limits,
enforcement
analytical
method,
oxidation/
reduction,
explodability,
storage
stability,
corrosion
characteristics,
and
density
(OPPTS
830.1550,
1670,
1750,
1800,
6314,
6316,
6317,
6320,
and
7000).
Data
requirements
for
the
Drexel
and
Platte
99%
Ts,
and
AgrEvo
97.5%
FI,
which
are
repackaged
from
EPA
registered
products,
will
be
satisfied
by
data
for
the
source
products.
All
product
specific
product
chemistry
data
are
required
for
the
Sureco
80%
FI,
Amvac
46%
FI,
and
AgrEvo
1%
FI.
Provided
that
the
registrants
submit
the
data
required
in
the
attached
data
summary
tables
for
the
carbaryl
MPs,
and
2
either
certify
that
the
suppliers
of
beginning
materials
and
the
manufacturing
processes
for
the
carbaryl
MPs
have
not
changed
since
the
last
comprehensive
product
chemistry
review
or
submit
complete
updated
product
chemistry
data
packages,
HED
has
no
objections
to
the
reregistration
of
carbaryl
with
respect
to
product
chemistry
data
requirements.
Residue
Chemistry
The
residue
chemistry
database
is
essentially
complete.
The
reregistration
requirements
for
plant
and
livestock
metabolism
are
fulfilled.
Acceptable
metabolism
studies
depicting
the
qualitative
nature
of
the
residues
in
lettuce,
radish,
soybean,
ruminants
and
poultry
have
been
submitted
and
evaluated.
In
addition,
adequate
magnitude
of
the
residue
data
are
available
on
the
following
crops:
alfalfa,
almond,
asparagus,
beans
(dried
and
succulent),
blueberry,
broccoli,
cabbage,
celery,
cherry,
citrus
fruits,
clover,
corn
(sweet
and
field),
cucurbits
(cantaloupes,
cucumbers
and
squash),
cranberry,
flax,
grape,
head
and
leaf
lettuce,
mustard
greens,
okra,
peanut,
peas
(dried
and
succulent),
pecan,
pepper,
pistachio,
pome
fruits,
potato,
prickly
pear
cactus,
raspberry,
rice,
sorghum,
soybean,
spinach,
stone
fruits,
strawberry,
sunflower,
sweet
potato,
tobacco,
tomato,
and
walnut.
The
following
data
gaps
remain
outstanding.
°
A
review
of
the
labels
and
supporting
residue
data
indicate
that
several
label
amendments
are
required.
Details
are
provided
in
the
attached
chapter.
°
The
requirement
for
acceptable
enforcement
methods
which
determine
residues
of
concern
in
plant
and
livestock
commodities
remains
outstanding.
°
The
requirements
for
storage
stability
data
are
not
satisfied
for
purposes
of
reregistration.
Additional
data
are
required
depicting
the
storage
stability
of
carbaryl
per
se
in
an
oilseed,
processed
commodities
of
an
oily
crop,
and
a
dried
fruit
stored
for
up
to
10
months.
In
addition,
the
registrant
is
relying
on
earlier
magnitude
of
the
residue
studies
that
are
not
supported
by
the
existing
storage
stability
data;
therefore,
additional
storage
stability
data
are
required.
The
required
data
must
reflect
storage
intervals
of
18
months
for
alfalfa
commodities,
15
months
for
potatoes,
22
months
for
wheat
commodities,
and
33
months
for
rangeland
grass.
In
addition,
if
the
registrant
wishes
to
rely
on
the
previously
submitted
sugar
beet
processing
study,
information
pertaining
to
sample
conditions
and
intervals
for
the
study
must
be
submitted.
°
For
the
purpose
of
reregistration,
the
requirements
for
storage
stability
data
for
carbaryl
residues
in
livestock
commodities
are
partially
satisfied.
Additional
information
on
the
storage
intervals
prior
to
analysis
for
metabolite
residues
in
the
cattle
feeding
study
is
required.
°
Separate
tolerances
on
many
commodities
need
to
be
reassigned
concomitant
with
establishing
tolerances
for
the
appropriate
crop
group
and
subgroup.
The
recommended
changes
are
summarized
in
Table
C
under
"Tolerances
Needed
Under
40
CFR
§180.169(
a),
crop
group/
subgroup
tolerances."
3
°
The
data
submitted
are
not
adequate
to
support
the
use
of
granular
(G)
formulations
of
carbaryl
on
leafy
vegetables.
Residues
of
carbaryl
found
in
leaf
lettuce
were
not
consistent.
Both
samples
of
lettuce
from
the
10%
G
treatment
had
substantially
higher
residues
(37.01
and
47.22
ppm)
than
one
of
the
samples
treated
with
the
FlC
(23.25
ppm).
Additionally,
all
residues
were
significantly
above
the
current
tolerance
of
10
ppm.
and
all
residue
data
submitted
in
support
of
the
tolerance
in
lettuce
(<
8.85
ppm).
No
explanation
for
the
higher
residues
was
given
by
the
registrant.
The
registrant
may
elect
to
repeat
the
side
by
side
trial
on
leaf
lettuce
again
or
submit
a
rationale
for
the
results
of
the
leaf
lettuce
study.
°
Data
are
required
depicting
residues
of
carbaryl
in/
on
grass
forage
harvested
immediately
(0
day)
following
the
last
of
two
applications
of
carbaryl
(WP
or
FlC)
at
1.5
lb
ai/
A
to
pasture.
A
total
of
12
field
trials
are
required
in
areas
throughout
the
U.
S.
°
Adequate
data
are
available
to
reassess
the
tolerances
for
residues
of
carbaryl
in/
on
dried
beans,
cowpeas,
lentils
and
peas
with
pods.
These
data
support
the
establishment
of
crop
subgroup
tolerances
for
edible
podded
legume
vegetables
(6A),
and
for
dried,
shelled
pea
and
bean
except
soybean
(6C).
However,
additional
residue
data
are
required
if
the
registrant
seeks
tolerances
for
residues
in/
on
succulent,
shelled
pea
and
bean
commodities.
A
total
of
12
tests,
six
tests
each
on
a
succulent,
shelled
cultivar
of
bean
and
garden
pea,
are
required
to
support
a
tolerance
for
residues
in/
on
the
succulent,
shelled
pea
and
bean
crop
subgroup
(6B).
The
registrant
is
referred
to
OPPTS
GLN
860.1500
for
the
number
and
distribution
of
tests
required.
°
Adequate
data
are
available
to
reassess
the
tolerance
for
wheat
forage
and
straw.
However,
the
Agency
now
considers
wheat
hay
a
significant
RAC
for
feed
purposes
(OPPTS
GLN
860.1000
Table
1.).
A
full
set
of
20
field
trials
as
specified
in
OPPTS
GLN
860.1500
are
required
depicting
carbaryl
residues
in/
on
wheat
hay.
When
all
the
field
trials
are
complete,
PHIs
and
tolerances
for
hay
based
on
the
field
trial
data
should
be
proposed.
Data
on
wheat
hay
will
be
translatable
to
proso
millet
hay.
°
The
registrant
intends
to
support
a
tolerance
for
residues
of
carbaryl
in/
on
imported
pineapples
(Aventis
personal
communication
with
C.
Olinger,
9/
24/
98
SMART
meeting).
Residue
data
are
required
depicting
residues
in/
on
pineapples
following
application
of
carbaryl
at
the
maximum
use
rate
and
minimum
PHI.
Five
trials
must
be
submitted,
three
from
Costa
Rica
and
two
from
Mexico.
°
The
registrant
does
not
intend
to
support
carbaryl
uses
on
avocados,
barley,
maple
sap,
oats,
rye,
and
sweet
sorghum;
however,
IR
4
has
indicated
(Correspondence
from
K.
Dorschner,
IR
4
Project,
9/
15/
94)
that
they
may
fulfill
the
residue
data
requirements
for
some
of
these
commodities.
These
data
have
not
been
submitted.
cc:
List
B
Rereg.
File
RDI:
WPhang
11/
7/
00,
WJHazel
10/
7
/2000
7509C:
FFort:
RRB1:
CM2:
Rm
722H:
703
305
7478:
11/
03/
2000
CARBARYL
Chemical
ID
No.
056801;
Case
0080
Product
Chemistry
Chapter
of
the
Reregistration
Eligibility
Decision
(RED)
Document
O
O
N
H
CH
3
CARBARYL
REREGISTRATION
ELIGIBILITY
DECISION:
PRODUCT
CHEMISTRY
CONSIDERATIONS
Chemical
ID
No.
056801;
Case
No.
0080
DESCRIPTION
OF
CHEMICAL
Carbaryl
[1
naphthyl
N
methylcarbamate]
is
a
broad
spectrum
insecticide
used
for
control
of
various
insects
on
numerous
varieties
of
fruits,
nuts,
and
field
and
vegetable
crops.
Empirical
Formula:
C12H11NO2
Molecular
Weight:
201.2
CAS
Registry
No.:
63
25
2
Chemical
ID
No.:
056801
IDENTIFICATION
OF
ACTIVE
INGREDIENT
Carbaryl
is
a
white
to
light
tan
solid
with
a
melting
point
of
142
C,
vapor
pressure
of
<0.005
mm
Hg
at
26
C,
specific
gravity
of
1.23
at
20
C,
and
octanol/
water
partition
coefficient
(Koc)
of
217.
Carbaryl
is
soluble
in
water
(40
ppm
at
25
C)
and
in
organic
solvents
including
dimethyl
formamide
(
#
45
g/
100
mL);
acetone,
cyclohexanone,
and
isophorone
(
#
25
g/
100
mL);
methylethyl
ketone
(
#
20
g/
100
mL);
dichloromethane
(
#
15
g/
100
mL);
ethanol
and
ethyl
acetate
(
#
10
g/
100
mL);
mixed
aromatic
solvents
and
xylene
(
#
3
g/
100
mL);
and
kerosene
(
#
1
g/
100
mL).
Carbaryl
hydrolyzes
rapidly
in
alkaline
solutions.
MANUFACTURING
USE
PRODUCTS
A
search
of
the
Reference
Files
System
(REFS)
conducted
10/
25/
00
identified
10
carbaryl
manufacturing
use
products
(MPs)
registered
under
Chemical
ID
No.
056801;
the
registered
carbaryl
MPs
are
listed
below
in
Table
1.
Only
the
registered
MPs
listed
below
are
subject
to
a
reregistration
eligibility
decision.
Table
1.
Registered
Carbaryl
Manufacturing
Use
Products.
3
Table
2.
Product
chemistry
data
requirements
specified
in
the
Carbaryl
FRSTR.
Product
OPPTS
830
Guidelines
Outstanding
99%
T
(EPA
Reg.
No.
264
324)
830.1600,
1620,
1670,
1700,
1750,
1800,
6313,
7000,
7370,
and
7950
97.5%
T
(EPA
Reg.
No.
264
325)
830.1670,
1750,
1800,
6314,
6316,
6317,
6320,
and
7000
80%
FI
(EPA
Reg.
No.
264
328)
830.1670,
1750,
1800,
6314,
6316,
6317,
6320,
and
7000
99%
T
(EPA
Reg.
No.
19713
75)
All
Group
A
and
B
Guidelines
50%
FI
(EPA
Reg.
No.
19713
369)
a
830.1670,
1750,
1800,
6314,
6316,
6317,
6320,
and
7000
97.5%
FI
(EPA
Reg.
No.
4816
270)
None;
data
requirements
to
be
satisfied
by
the
source
product.
46%
FI
(EPA
Reg.
No.
5481
190)
All
Group
A
and
B
Guidelines.
a
Based
on
data
submitted
by
Aventis.
The
current
status
of
the
product
chemistry
data
requirements
for
the
carbaryl
manufacturing
use
products
is
presented
in
the
attached
data
summary
tables.
Refer
to
these
tables
for
a
listing
of
the
outstanding
product
chemistry
data
requirements.
CONCLUSIONS
All
pertinent
product
chemistry
data
requirements
are
satisfied
for
the
Aventis
99%
T,
except
that
data
are
required
for
UV/
visible
absorption
(OPPTS
830.7050).
For
the
Aventis
97.5%
and
80%
FIs,
and
the
Drexel
50%
FI,
additional
data
are
required
concerning
product
identity
and
composition,
discussion
of
formation
of
impurities,
certified
limits,
enforcement
analytical
method,
oxidation/
reduction,
explodability,
storage
stability
corrosion
characteristics,
and
density
(OPPTS
830.1550,
1670,
1750,
1800,
6314,
6316,
6317,
6320,
and
7000).
Data
requirements
for
the
Drexel
and
Platte
99%
Ts,
and
AgrEvo
97.5%
FI,
which
are
repackaged
from
EPA
registered
products,
will
be
satisfied
by
data
for
the
source
products.
All
productspecific
product
chemistry
data
are
required
for
the
Sureco
80%
FI,
Amvac
46%
FI,
and
AgrEvo
1%
FI.
Provided
that
the
registrants
submit
the
data
required
in
the
attached
data
summary
tables
for
the
carbaryl
MPs,
and
either
certify
that
the
suppliers
of
beginning
materials
and
the
manufacturing
processes
for
the
carbaryl
MPs
have
not
changed
since
the
last
comprehensive
product
chemistry
review
or
submit
complete
updated
product
chemistry
data
packages,
HED
has
no
objections
to
the
reregistration
of
carbaryl
with
respect
to
product
chemistry
data
requirements.
AGENCY
MEMORANDA
CITED
IN
THIS
DOCUMENT
CBRS
No(
s).:
8724
DP
Barcode(
s):
D169720
Subject:
Rhone
Poulenc
Ag
Company:
Response
to
the
Carbaryl
Reregistration
Standard:
Residue
and
Product
Chemistry
Comments
From:
R.
Perfetti
2
Formulation
EPA
Reg.
No.
Registrant
99%
T
264
324
Aventis
Ag
Company
(formerly
Union
Carbide)
97.5%
FI
a
264
325
80%
FI
264
328
99%
T
b
19713
75
Drexel
Chemical
Company
50%
FI
c
19713
369
99%
T
b
34704
707
Platte
Chemical
Company
Inc.
97.5%
FI
b
4816
270
AgrEvo
Environmental
Health
(formerly
Fairfield
American)
1%
FI
4816
407
80%
FI
769
971
Sureco
Inc.
46%
FI
5481
190
Amvac
Chemical
Corporation
a
Although
REFS
identifies
this
product
as
a
technical
(T),
it
is
appropriately
identified
as
an
formulation
intermediate
(FI)
because
it
is
formulated
from
a
registered
technical
product.
b
Repackaged
from
an
EPA
registered
product;
confirmed
for
the
Drexel
99%
T
(EPA
Reg.
No.
19713
75)
subsequent
to
the
FRSTR.
c
Transferred
from
Aventis
(EPA
Reg.
No.
264
327;
7/
15/
92).
REGULATORY
BACKGROUND
The
Carbaryl
Reregistration
Standard
dated
6/
11/
82
and
Guidance
Document
dated
3/
30/
84
required
additional
generic
and
product
specific
product
chemistry
data
for
the
registered
carbaryl
MPs.
The
Carbaryl
(FRSTR)
Reregistration
Standard
dated
5/
3/
88
reviewed
data
submitted
in
response
to
the
Guidance
Document
and
summarized
the
outstanding
data
requirements
for
the
reregistration
of
carbaryl.
Additional
data
requirements
listed
in
the
FRSTR
are
presented
in
Table
2.
The
FRSTR
did
not
address
the
AgrEvo
1%
FI
(EPA
Reg.
No.
4816
407),
which
was
registered
3/
31/
72;
the
Platte
99%
T
(EPA
Reg.
No.
34704
707)
and
Sureco
80%
FI
(EPA
Reg.
No.
769
971)
were
registered
subsequent
to
issuance
of
the
FRSTR.
4
To:
W.
Burnam
and
L.
Rossi
Dated:
11/
1/
91
MRID(
s):
41982601
CBRS
No(
s).:
10083
DP
Barcode(
s):
D179698
Subject:
Rhone
Poulenc
Ag
Company:
Response
to
the
Carbaryl
Reregistration
Standard:
Nitrosamine
&
Stability
Considerations.
From:
K.
Dockter
To:
L.
Propst/
J.
Edwards
Dated:
7/
14/
92
MRID(
s):
42318501
CBRS
No(
s).:
11101
DP
Barcode(
s):
D186160
Subject:
Response
to
the
Carbaryl
Reregistration
Standard:
Product
Chemistry
From:
R.
Perfetti
To:
L.
Rossi
and
E.
Saito
Dated:
1/
29/
93
MRID(
s):
None
CBRS
No(
s).:
11201
DP
Barcode(
s):
D186515
Subject:
Response
to
the
Carbaryl
Reregistration
Standard:
Product
Chemistry.
From:
R.
Perfetti
To:
L.
Rossi
and
E.
Saito
Dated:
4/
21/
93
MRID(
s):
42583901
and
42583902
5
CBRS
No(
s).:
12225
DP
Barcode(
s):
D193013
Subject:
Carbaryl
Reregistration:
List
A
Chemical
No.
056801;
Case
No.
0080.
Rhone
Poulenc
Response
to
the
Carbaryl
Product
Chemistry
Data
Requirements
Regarding
Dissociation
Constant
and
pH
(Guideline
Nos.
63
10
and
63
12).
From:
F.
Toghrol
To:
L.
Rossi/
L.
Propst
Dated:
1/
26/
94
MRID(
s):
42832401
CBRS
No(
s).:
13127
DP
Barcode(
s):
D198578
Subject:
Carbaryl.
Rhone
Poulenc
1/
4/
94
Response
[62
3
data
for
EPA
Reg.
264
324]
to
5/
13/
93
Agency
Letter
[RE:
5/
3/
88
FRSTR]
Rereg.
Case
0080.
From:
K.
Dockter
To:
J.
Loranger
Dated:
4/
29/
94
MRID(
s):
43075801
CBRS
No(
s).:
15442
DP
Barcode(
s):
D214535
Subject:
Carbaryl
(056801)
Reregistration
Case
No.
0080,
Drexel
Request
for
Product
Chemistry
Generic
Data
Exemption
(GDE),
New
Confidential
Statement
of
Formula.
From:
S.
Hummel
To:
J.
Loranger/
L.
Propst
Dated:
5/
8/
95
MRID(
s):
None
6
PRODUCT
CHEMISTRY
CITATIONS
Bibliographic
citations
include
only
MRIDs
containing
data
which
fulfill
data
requirements.
References
(cited):
00151776
Union
Carbide
Agricultural
Products
Co.,
Inc.
(1984)
The
Name,
Chemical
Identity
and
Composition
of
the
Pesticide
Chemical
Sevin.
Unpublished
compilation.
336
p.
41982601
McDaniel,
R.;
Weiler,
D.
(1987)
Vapor
Pressure
Determination
of
Carbaryl:
Final
Report:
Lab
Project
Number:
40196.
Unpublished
study
prepared
by
Rhone
Poulenc
Ag
Co.
35
p.
42318501
Siemann,
L.
(1992)
Product
Chemistry
on
Technical
Grade
Carbaryl
in
Support
of
Registration:
Analysis
for
Nitrosoamines
and
Stability
Study:
[Interim
Report]:
Lab
Project
Number:
6489
F.
Unpublished
study
prepared
by
Midwest
Research
Institute.
26
p.
42583901
Helfant,
L.
(1992)
Sevin
Brand
99%
Technical
Carbaryl
Insecticide:
Product
Identity
and
Composition
Series
61:
Lab
Project
Number:
AC
92
014:
41330.
Unpublished
study
prepared
by
Rhone
Poulenc
Ag
Co.
42
p.
42583902
Siemann,
L.
(1992)
Product
Chemistry
on
Technical
Grade
Carbaryl
in
Support
of
Registration
Analysis
for
Nitrosoamines
and
Stability
Study:
Lab
Project
Number:
6489
F.
Unpublished
study
prepared
by
Midwest
Research
Institute.
149
p.
42832401
Siemann,
L.
(1993)
Carbaryl
Product
Chemistry:
Lab
Project
Number:
3424
F.
Unpublished
study
prepared
by
Midwest
Research
Institute.
21
p.
43075801
Siemann,
L.
(1993)
Method
Validation
for
Analysis
of
Carbaryl:
Lab
Project
Number:
3521/
F.
Unpublished
study
prepared
by
Midwest
Research
Institute.
127
p.
7
Case
No.
0080
Chemical
No.
056801
Case
Name:
Carbaryl
Registrant:
Aventis
Ag
Company
Product(
s):
99%
T
(EPA
Reg
No.
264
324)
PRODUCT
CHEMISTRY
DATA
SUMMARY
Guideline
Number
Requirement
Are
Data
Requirements
Fulfilled?
1
MRID
Number
2
830.1550
Product
identity
and
composition
Y
00151776,
42583901
3
830.1600
Description
of
materials
used
to
produce
the
product
Y
00151776,
42583901
3
830.1620
Description
of
production
process
Y
00151776,
42583901
3
830.1670
Discussion
of
formation
of
impurities
Y
00151776,
42583901
3
830.1700
Preliminary
analysis
Y
00151776,
42318501
4
,
42583902
3
830.1750
Certified
limits
Y
00151776,
42583901
3
830.1800
Enforcement
analytical
method
Y
00151776,
43075801
5
830.6302
Color
Y
00151776
830.6303
Physical
state
Y
00151776
830.6304
Odor
Y
00151776
830.6313
Stability
to
normal
and
elevated
temperature,
metals,
and
metal
ions
Y
00151776,
42318501
4
830.6314
Oxidation/
reduction:
chemical
incompatibility
Y
00151776
830.6315
Flammability
N/
A
6
830.6316
Explodability
Y
00151776
830.6317
Storage
stability
Y
00151776
830.6319
Miscibility
N/
A
6
830.6320
Corrosion
characteristics
Y
00151776
830.7000
pH
Y
42832401
7
830.7050
UV/
visible
absorption
N
8
830.7100
Viscosity
N/
A
6
830.7200
Melting
point/
melting
range
Y
00151776
830.7220
Boiling
point/
boiling
range
N/
A
6
830.7300
Density/
relative
density/
bulk
density
Y
00151776
830.7370
Dissociation
constants
in
water
Y
42832401
7
830.7550
Partition
coefficient
(n
octanol/
water),
shake
flask
method
Y
00151776
830.7840
Water
solubility:
column
elution
method;
shake
flask
method
Y
00151776
830.7950
Vapor
pressure
Y
00151776,
41982601
9
1
Y
=
Yes;
N
=
No;
N/
A
=
Not
Applicable.
Aventis
indicated
(CBRS
No.
11101,
D186160,
1/
29/
93,
R.
Perfetti)
that
the
alternate
formulation
for
which
data
were
required
in
the
FRSTR
is
no
longer
produced.
2
MRID
00151776
was
reviewed
initially
under
a
HED
Memorandum
from
W.
T.
Chin
dated
9/
18/
85
and
reevaluated
in
the
Carbaryl
(FRSTR)
Reregistration
Standard
dated
5/
3/
88;
remaining
references
were
reviewed
as
noted.
3
CBRS
No.
11201,
D186515,
4/
21/
93,
R.
Perfetti.
4
CBRS
No.
10083,
D179698,
7/
14/
92,
K.
Dockter.
5
CBRS
No.
13127,
D198578,
4/
29/
94,
K.
Dockter.
6
Data
are
not
required
because
the
T/
TGAI
is
a
solid
at
room
temperature.
7
CBRS
No.
12225,
D193013,
1/
26/
94,
F.
Toghrol.
8
The
OPPTS
Series
830,
Product
Properties
Test
Guidelines
require
data
pertaining
to
UV/
visible
absorption
for
the
PAI.
9
CBRS
No.
8724,
D169720,
11/
1/
91,
R.
Perfetti.
8
Case
No.
0080
Chemical
No.
056801
Case
Name:
Carbaryl
Registrant:
Aventis
Ag
Company
Product(
s):
97.5%
FI
(EPA
Reg.
No.
264
325)
PRODUCT
CHEMISTRY
DATA
SUMMARY
Guideline
Number
Requirement
Are
Data
Requirements
Fulfilled?
1
MRID
Number
2
830.1550
Product
identity
and
composition
N
3
00151776
830.1600
Description
of
materials
used
to
produce
the
product
Y
00151776
830.1650
Description
of
formulation
process
Y
00151776
830.1670
Discussion
of
formation
of
impurities
N
4
00151776
830.1700
Preliminary
analysis
N/
A
5
830.1750
Certified
limits
N
3
00151776
830.1800
Enforcement
analytical
method
N
6
00151776
830.6302
Color
Y
00151776
830.6303
Physical
state
Y
00151776
830.6304
Odor
Y
00151776
830.6313
Stability
to
normal
and
elevated
temperature,
metals,
and
metal
ions
N/
A
5
830.6314
Oxidation/
reduction:
chemical
incompatibility
N
830.6315
Flammability
N/
A
7
830.6316
Explodability
N
830.6317
Storage
stability
N
830.6319
Miscibility
N/
A
7
830.6320
Corrosion
characteristics
N
830.7000
pH
N
830.7050
UV/
visible
absorption
N/
A
5
830.7100
Viscosity
N/
A
7
830.7200
Melting
point/
melting
range
N/
A
5
830.7220
Boiling
point/
boiling
range
N/
A
5
830.7300
Density/
relative
density/
bulk
density
Y
00151776
830.7370
Dissociation
constants
in
water
N/
A
5
830.7550
Partition
coefficient
(n
octanol/
water),
shake
flask
method
N/
A
5
830.7840
Water
solubility:
column
elution
method;
shake
flask
method
N/
A
5
830.7950
Vapor
pressure
N/
A
5
1
Y
=
Yes;
N
=
No;
N/
A
=
Not
Applicable.
Although
REFS
identifies
this
product
as
a
T,
it
is
appropriately
identified
as
an
FI
because
it
is
formulated
from
a
registered
technical
product.
2
MRID
00151776
was
reviewed
initially
under
a
HED
Memorandum
from
W.
T.
Chin
dated
9/
18/
85
and
reevaluated
in
the
Carbaryl
(FRSTR)
Reregistration
Standard
dated
5/
3/
88.
3
Product
identity,
nominal
concentrations
and
proposed
certified
limits
must
be
submitted
on
EPA
Form
8570
4.
4
A
discussion
must
be
submitted
concerning
the
possible
formation
of
impurities
associated
with
the
inert
ingredients
in
the
MP
and
the
potential
for
formation
of
nitrosamines
in
the
formulation
process
or
in
storage.
5
Data
requirements
for
the
TGAI
will
be
satisfied
by
data
for
the
technical
source
product.
6
Supporting
validation
data
must
be
submitted
for
the
enforcement
method
used
to
quantitate
the
active
ingredient
in
the
formulated
product.
7
Data
are
not
required
because
the
MP
is
a
solid
at
room
temperature.
9
Case
No.
0080
Chemical
No.
056801
Case
Name:
Carbaryl
Registrant:
Aventis
Ag
Company
Product(
s):
80%
FI
(EPA
Reg.
No.
264
328)
PRODUCT
CHEMISTRY
DATA
SUMMARY
Guideline
Number
Requirement
Are
Data
Requirements
Fulfilled?
1
MRID
Number
2
830.1550
Product
identity
and
composition
N
3
00151776
830.1600
Description
of
materials
used
to
produce
the
product
Y
00151776
830.1650
Description
of
formulation
process
Y
00151776
830.1670
Discussion
of
formation
of
impurities
N
4
00151776
830.1700
Preliminary
analysis
N/
A
5
830.1750
Certified
limits
N
3
00151776
830.1800
Enforcement
analytical
method
N
6
00151776
830.6302
Color
Y
00151776
830.6303
Physical
state
Y
00151776
830.6304
Odor
Y
00151776
830.6313
Stability
to
normal
and
elevated
temperature,
metals,
and
metal
ions
N/
A
5
830.6314
Oxidation/
reduction:
chemical
incompatibility
N
830.6315
Flammability
N/
A
7
830.6316
Explodability
N
830.6317
Storage
stability
N
830.6319
Miscibility
N/
A
7
830.6320
Corrosion
characteristics
N
830.7000
pH
N
830.7050
UV/
visible
absorption
N/
A
5
830.7100
Viscosity
N/
A
7
830.7200
Melting
point/
melting
range
N/
A
5
830.7220
Boiling
point/
boiling
range
N/
A
5
830.7300
Density/
relative
density/
bulk
density
Y
00151776
830.7370
Dissociation
constants
in
water
N/
A
5
830.7550
Partition
coefficient
(n
octanol/
water),
shake
flask
method
N/
A
5
830.7840
Water
solubility:
column
elution
method;
shake
flask
method
N/
A
5
830.7950
Vapor
pressure
N/
A
5
1
Y
=
Yes;
N
=
No;
N/
A
=
Not
Applicable.
2
MRID
00151776
was
reviewed
initially
under
a
HED
Memorandum
from
W.
T.
Chin
dated
9/
18/
85
and
reevaluated
in
the
Carbaryl
(FRSTR)
Reregistration
Standard
dated
5/
3/
88.
3
Product
identity,
nominal
concentrations
and
proposed
certified
limits
must
be
submitted
on
EPA
Form
8570
4.
4
A
discussion
must
be
submitted
of
the
possible
formation
of
impurities
associated
with
the
inert
ingredients
in
the
MP
and
the
potential
for
formation
of
nitrosamines
in
the
formulation
process
or
in
storage.
5
Data
requirements
for
the
TGAI
will
be
satisfied
by
data
for
the
technical
source
product.
6
Supporting
validation
data
must
be
submitted
for
the
enforcement
method
used
to
quantitate
the
active
ingredient
in
the
formulated
product.
7
Data
are
not
required
because
the
MP
is
a
solid
at
room
temperature.
10
Case
No.
0080
Chemical
No.
056801
Case
Name:
Carbaryl
Registrant:
Drexel
Chemical
Company
Product(
s):
99%
T
(EPA
Reg
No.
19713
75)
PRODUCT
CHEMISTRY
DATA
SUMMARY
Guideline
Number
Requirement
Are
Data
Requirements
Fulfilled?
1
MRID
Number
2
830.1550
Product
identity
and
composition
Y
CSF
date
not
specified
CSF
dated
8/
7/
95
830.1600
Description
of
materials
used
to
produce
the
product
N/
A
830.1620
Description
of
production
process
N/
A
830.1670
Discussion
of
formation
of
impurities
N/
A
830.1700
Preliminary
analysis
N/
A
830.1750
Certified
limits
N/
A
830.1800
Enforcement
analytical
method
N/
A
830.6302
Color
N/
A
830.6303
Physical
state
N/
A
830.6304
Odor
N/
A
830.6313
Stability
to
normal
and
elevated
temperature,
metals,
and
metal
ions
N/
A
830.6314
Oxidation/
reduction:
chemical
incompatibility
N/
A
830.6315
Flammability
N/
A
830.6316
Explodability
N/
A
830.6317
Storage
stability
N/
A
830.6319
Miscibility
N/
A
830.6320
Corrosion
characteristics
N/
A
830.7000
pH
N/
A
830.7050
UV/
visible
absorption
N/
A
830.7100
Viscosity
N/
A
830.7200
Melting
point/
melting
range
N/
A
830.7220
Boiling
point/
boiling
range
N/
A
830.7300
Density/
relative
density/
bulk
density
N/
A
830.7370
Dissociation
constants
in
water
N/
A
830.7550
Partition
coefficient
(n
octanol/
water),
shake
flask
method
N/
A
830.7840
Water
solubility:
column
elution
method;
shake
flask
method
N/
A
830.7950
Vapor
pressure
N/
A
1
Y
=
Yes;
N
=
No;
N/
A
=
Not
Applicable.
2
The
CSF
(date
not
specified)
reviewed
under
CBRS
No.
15442,
D214535,
5/
8/
95,
S.
Hummel,
and
an
updated
CSF
dated
8/
7/
95
(from
the
product
jacket),
confirm
that
this
product
is
repackaged
from
an
EPA
registered
product;
all
data
requirements
will
be
fulfilled
by
data
for
the
source
product.
11
Case
No.
0080
Chemical
No.
056801
Case
Name:
Carbaryl
Registrant:
Drexel
Chemical
Company
Product(
s):
50%
FI
(EPA
Reg.
No.
19713
369)
PRODUCT
CHEMISTRY
DATA
SUMMARY
Guideline
Number
Requirement
Are
Data
Requirements
Fulfilled?
1
MRID
Number
2
830.1550
Product
identity
and
composition
N
3
00151776
830.1600
Description
of
materials
used
to
produce
the
product
Y
00151776
830.1650
Description
of
formulation
process
Y
00151776
830.1670
Discussion
of
formation
of
impurities
N
4
00151776
830.1700
Preliminary
analysis
N/
A
5
830.1750
Certified
limits
N
3
00151776
830.1800
Enforcement
analytical
method
N
6
00151776
830.6302
Color
Y
00151776
830.6303
Physical
state
Y
00151776
830.6304
Odor
Y
00151776
830.6313
Stability
to
normal
and
elevated
temperature,
metals,
and
metal
ions
N/
A
5
830.6314
Oxidation/
reduction:
chemical
incompatibility
N
830.6315
Flammability
N/
A
7
830.6316
Explodability
N
830.6317
Storage
stability
N
830.6319
Miscibility
N/
A
7
830.6320
Corrosion
characteristics
N
830.7000
pH
N
830.7050
UV/
visible
absorption
N/
A
5
830.7100
Viscosity
N/
A
7
830.7200
Melting
point/
melting
range
N/
A
5
830.7220
Boiling
point/
boiling
range
N/
A
5
830.7300
Density/
relative
density/
bulk
density
Y
00151776
830.7370
Dissociation
constants
in
water
N/
A
5
830.7550
Partition
coefficient
(n
octanol/
water),
shake
flask
method
N/
A
5
830.7840
Water
solubility:
column
elution
method;
shake
flask
method
N/
A
5
830.7950
Vapor
pressure
N/
A
5
1
Y
=
Yes;
N
=
No;
N/
A
=
Not
Applicable.
This
product
was
transferred
from
Aventis
(EPA
Reg.
No.
264
327);
the
data
summary
table
includes
data
submitted
by
Aventis.
Drexel
must
confirm
that
the
manufacturing
process
and
site
have
not
changed
since
the
product
transfer;
otherwise,
all
product
chemistry
data
will
be
required.
2
MRID
00151776
was
reviewed
initially
under
a
HED
Memorandum
from
W.
T.
Chin
dated
9/
18/
85
and
reevaluated
in
the
Carbaryl
(FRSTR)
Reregistration
Standard
dated
5/
3/
88.
3
Product
identity,
nominal
concentrations
and
proposed
certified
limits
must
be
submitted
on
EPA
Form
8570
4.
4
A
discussion
must
be
submitted
of
the
possible
formation
of
impurities
associated
with
the
inert
ingredients
in
the
MP
and
the
potential
for
formation
of
nitrosamines
in
the
formulation
process
or
in
storage.
5
Data
requirements
for
the
TGAI
will
be
satisfied
by
data
for
the
technical
source
product.
6
Supporting
validation
data
must
be
submitted
for
the
enforcement
method
used
to
quantitate
the
active
ingredient
in
the
formulated
product.
7
Data
are
not
required
because
the
MP
is
a
solid
at
room
temperature.
12
Case
No.
0080
Chemical
No.
056801
Case
Name:
Carbaryl
Registrant:
Platte
Chemical
Company
Product(
s):
99%
T
(EPA
Reg
No.
34704
707)
PRODUCT
CHEMISTRY
DATA
SUMMARY
Guideline
Number
Requirement
Are
Data
Requirements
Fulfilled?
1
MRID
Number
2
830.1550
Product
identity
and
composition
Y
CSF
dated
4/
12/
91
830.1600
Description
of
materials
used
to
produce
the
product
N/
A
830.1620
Description
of
production
process
N/
A
830.1670
Discussion
of
formation
of
impurities
N/
A
830.1700
Preliminary
analysis
N/
A
830.1750
Certified
limits
N/
A
830.1800
Enforcement
analytical
method
N/
A
830.6302
Color
N/
A
830.6303
Physical
state
N/
A
830.6304
Odor
N/
A
830.6313
Stability
to
normal
and
elevated
temperature,
metals,
and
metal
ions
N/
A
830.6314
Oxidation/
reduction:
chemical
incompatibility
N/
A
830.6315
Flammability
N/
A
830.6316
Explodability
N/
A
830.6317
Storage
stability
N/
A
830.6319
Miscibility
N/
A
830.6320
Corrosion
characteristics
N/
A
830.7000
pH
N/
A
830.7050
UV/
visible
absorption
N/
A
830.7100
Viscosity
N/
A
830.7200
Melting
point/
melting
range
N/
A
830.7220
Boiling
point/
boiling
range
N/
A
830.7300
Density/
relative
density/
bulk
density
N/
A
830.7370
Dissociation
constants
in
water
N/
A
830.7550
Partition
coefficient
(n
octanol/
water),
shake
flask
method
N/
A
830.7840
Water
solubility:
column
elution
method;
shake
flask
method
N/
A
830.7950
Vapor
pressure
N/
A
1
Y
=
Yes;
N
=
No;
N/
A
=
Not
Applicable.
2
The
CSF
dated
4/
12/
91
(from
the
product
jacket)
confirms
that
this
product
is
repackaged
from
an
EPA
registered
product;
all
data
requirements
will
be
fulfilled
by
data
for
the
source
product.
We
note
that
an
updated
CSF
should
be
submitted
reflecting
the
nominal
concentration
of
the
active
ingredient
in
the
product.
13
Case
No.
0080
Chemical
No.
056801
Case
Name:
Carbaryl
Registrant:
AgrEvo
Environmental
Health
Product(
s):
97.5%
T
(EPA
Reg
No.
4816
270)
PRODUCT
CHEMISTRY
DATA
SUMMARY
Guideline
Number
Requirement
Are
Data
Requirements
Fulfilled?
1
MRID
Number
2
830.1550
Product
identity
and
composition
Y
CSF
dated
7/
24/
91
830.1600
Description
of
materials
used
to
produce
the
product
N/
A
830.1620
Description
of
production
process
N/
A
830.1670
Discussion
of
formation
of
impurities
N/
A
830.1700
Preliminary
analysis
N/
A
830.1750
Certified
limits
N/
A
830.1800
Enforcement
analytical
method
N/
A
830.6302
Color
N/
A
830.6303
Physical
state
N/
A
830.6304
Odor
N/
A
830.6313
Stability
to
normal
and
elevated
temperature,
metals,
and
metal
ions
N/
A
830.6314
Oxidation/
reduction:
chemical
incompatibility
N/
A
830.6315
Flammability
N/
A
830.6316
Explodability
N/
A
830.6317
Storage
stability
N/
A
830.6319
Miscibility
N/
A
830.6320
Corrosion
characteristics
N/
A
830.7000
pH
N/
A
830.7050
UV/
visible
absorption
N/
A
830.7100
Viscosity
N/
A
830.7200
Melting
point/
melting
range
N/
A
830.7220
Boiling
point/
boiling
range
N/
A
830.7300
Density/
relative
density/
bulk
density
N/
A
830.7370
Dissociation
constants
in
water
N/
A
830.7550
Partition
coefficient
(n
octanol/
water),
shake
flask
method
N/
A
830.7840
Water
solubility:
column
elution
method;
shake
flask
method
N/
A
830.7950
Vapor
pressure
N/
A
1
Y
=
Yes;
N
=
No;
N/
A
=
Not
Applicable.
2
The
CSF
dated
7/
24/
91
(from
the
product
jacket)
confirms
that
this
product
is
repackaged
from
an
EPA
registered
product;
all
data
requirements
will
be
fulfilled
by
data
for
the
source
product.
We
note
that
an
updated
CSF
should
be
submitted
reflecting
the
nominal
concentration
of
the
active
ingredient
in
the
product.
14
Case
No.
0080
Chemical
No.
056801
Case
Name:
Carbaryl
Registrant:
AgrEvo
Environmental
Health
Product(
s):
1%
FI
(EPA
Reg
No.
4816
407)
PRODUCT
CHEMISTRY
DATA
SUMMARY
Guideline
Number
Requirement
Are
Data
Requirements
Fulfilled?
1
MRID
Number
2
830.1550
Product
identity
and
composition
N
CSF
dated
7/
24/
91
830.1600
Description
of
materials
used
to
produce
the
product
N
830.1650
Description
of
formulation
process
N
830.1670
Discussion
of
formation
of
impurities
N
830.1700
Preliminary
analysis
N/
A
3
830.1750
Certified
limits
N
830.1800
Enforcement
analytical
method
N
830.6302
Color
N
830.6303
Physical
state
N
830.6304
Odor
N
830.6313
Stability
to
normal
and
elevated
temperature,
metals,
and
metal
ions
N/
A
3
830.6314
Oxidation/
reduction:
chemical
incompatibility
N
830.6315
Flammability
N
830.6316
Explodability
N
830.6317
Storage
stability
N
830.6319
Miscibility
N
830.6320
Corrosion
characteristics
N
830.7000
pH
N
830.7050
UV/
visible
absorption
N/
A
3
830.7100
Viscosity
N
830.7200
Melting
point/
melting
range
N/
A
3
830.7220
Boiling
point/
boiling
range
N/
A
3
830.7300
Density/
relative
density/
bulk
density
N
830.7370
Dissociation
constants
in
water
N/
A
3
830.7550
Partition
coefficient
(n
octanol/
water),
shake
flask
method
N/
A
3
830.7840
Water
solubility:
column
elution
method;
shake
flask
method
N/
A
3
830.7950
Vapor
pressure
N/
A
3
1
Y
=
Yes;
N
=
No;
N/
A
=
Not
Applicable.
2
The
CSF
dated
7/
24/
91
(from
the
product
jacket)
confirms
that
this
product
is
formulated
from
an
EPA
registered
product.
3
TGAI
data
requirements
will
be
satisfied
by
data
for
the
technical
source
product.
15
Case
No.
0080
Chemical
No.
056801
Case
Name:
Carbaryl
Registrant:
Sureco
Inc.
Product(
s):
80%
FI
(EPA
Reg
No.
769
971)
PRODUCT
CHEMISTRY
DATA
SUMMARY
Guideline
Number
Requirement
Are
Data
Requirements
Fulfilled?
1
MRID
Number
2
830.1550
Product
identity
and
composition
N
CSF
dated
9/
23/
94
830.1600
Description
of
materials
used
to
produce
the
product
N
830.1650
Description
of
formulation
process
N
830.1670
Discussion
of
formation
of
impurities
N
830.1700
Preliminary
analysis
N/
A
3
830.1750
Certified
limits
N
830.1800
Enforcement
analytical
method
N
830.6302
Color
N
830.6303
Physical
state
N
830.6304
Odor
N
830.6313
Stability
to
normal
and
elevated
temperature,
metals,
and
metal
ions
N/
A
3
830.6314
Oxidation/
reduction:
chemical
incompatibility
N
830.6315
Flammability
N
830.6316
Explodability
N
830.6317
Storage
stability
N
830.6319
Miscibility
N
830.6320
Corrosion
characteristics
N
830.7000
pH
N
830.7050
UV/
visible
absorption
N/
A
3
830.7100
Viscosity
N
830.7200
Melting
point/
melting
range
N/
A
3
830.7220
Boiling
point/
boiling
range
N/
A
3
830.7300
Density/
relative
density/
bulk
density
N
830.7370
Dissociation
constants
in
water
N/
A
3
830.7550
Partition
coefficient
(n
octanol/
water),
shake
flask
method
N/
A
3
830.7840
Water
solubility:
column
elution
method;
shake
flask
method
N/
A
3
830.7950
Vapor
pressure
N/
A
3
1
Y
=
Yes;
N
=
No;
N/
A
=
Not
Applicable.
A
letter
from
L.
Howard,
Aventis,
to
D.
Edwards,
EPA,
dated
9/
14/
94
authorizes
use
of
Aventis
data
to
satisfy
data
requirements
for
this
product;
however,
until
a
determination
concerning
substantial
similarity
for
the
two
products
has
been
made,
all
product
chemistry
data
requirements
remain
outstanding.
2
The
CSF
available
from
the
product
jacket
confirms
that
this
product
is
formulated
from
an
EPA
registered
product.
3
TGAI
data
requirements
will
be
satisfied
by
data
for
the
technical
source
product.
16
Case
No.
0080
Chemical
No.
056801
Case
Name:
Carbaryl
Registrant:
Amvac
Chemical
Corporation
Product(
s):
46%
FI
(EPA
Reg
No.
5481
190)
PRODUCT
CHEMISTRY
DATA
SUMMARY
Guideline
Number
Requirement
Are
Data
Requirements
Fulfilled?
1
MRID
Number
2
830.1550
Product
identity
and
composition
N
CSF
dated
5/
18/
84
830.1600
Description
of
materials
used
to
produce
the
product
N
830.1650
Description
of
formulation
process
N
830.1670
Discussion
of
formation
of
impurities
N
830.1700
Preliminary
analysis
N/
A
3
830.1750
Certified
limits
N
830.1800
Enforcement
analytical
method
N
830.6302
Color
N
830.6303
Physical
state
N
830.6304
Odor
N
830.6313
Stability
to
normal
and
elevated
temperature,
metals,
and
metal
ions
N/
A
3
830.6314
Oxidation/
reduction:
chemical
incompatibility
N
830.6315
Flammability
N
830.6316
Explodability
N
830.6317
Storage
stability
N
830.6319
Miscibility
N
830.6320
Corrosion
characteristics
N
830.7000
pH
N
830.7050
UV/
visible
absorption
N/
A
3
830.7100
Viscosity
N
830.7200
Melting
point/
melting
range
N/
A
3
830.7220
Boiling
point/
boiling
range
N/
A
3
830.7300
Density/
relative
density/
bulk
density
N
830.7370
Dissociation
constants
in
water
N/
A
3
830.7550
Partition
coefficient
(n
octanol/
water),
shake
flask
method
N/
A
3
830.7840
Water
solubility:
column
elution
method;
shake
flask
method
N/
A
3
830.7950
Vapor
pressure
N/
A
3
1
Y
=
Yes;
N
=
No;
N/
A
=
Not
Applicable.
2
The
CSF
dated
5/
18/
84
(from
the
product
jacket)
confirms
that
this
product
is
manufactured
from
an
EPAregistered
product.
3
TGAI
data
requirements
will
be
satisfied
by
data
for
the
technical
source
product.
CARBARYL
Chemical
ID
No.
056801;
Case
0080
Residue
Chemistry
Chapter
of
the
Reregistration
Eligibility
Decision
(RED)
Document
CARBARYL
REREGISTRATION
ELIGIBILITY
DECISION
RESIDUE
CHEMISTRY
CONSIDERATIONS
PC
Code
056801;
Case
0080
TABLE
OF
CONTENTS
page
INTRODUCTION
.............................................................
1
REGULATORY
BACKGROUND
................................................
1
SUMMARY
OF
SCIENCE
FINDINGS
............................................
2
GLN
860.1300:
Nature
of
the
Residue
Plants
.................................
4
GLN
860.1300:
Nature
of
the
Residue
Livestock
...............................
5
GLN
860.1340:
Residue
Analytical
Methods
...................................
5
GLN
860.1360:
Multiresidue
Methods
........................................
6
GLN
860.1380:
Storage
Stability
Data
Plants
.................................
7
GLN
860.1380:
Storage
Stability
Data
Livestock
..............................
8
GLN
860.1500:
Crop
Field
Trials
............................................
8
GLN
860.1520:
Processed
Food/
Feed
.......................................
11
GLN
860.1480:
Meat,
Milk,
Poultry,
Eggs
....................................
12
GLN
860.1400:
Water,
Fish,
and
Irrigated
Crops
...............................
13
GLN
860.1460:
Food
Handling
............................................
14
GLNs
860.1850
and
860.1900:
Confined/
Field
Accumulation
in
Rotational
Crops
....
14
FOOD/
FEED
USE
PATTERN
..................................................
15
TOLERANCE
REASSESSMENT
SUMMARY
....................................
78
Tolerances
Listed
Under
40
CFR
§180.169(
a),
(b),
(c),
(d),
and
(e)
.................
80
Tolerance
Listed
Under
40
CFR
§180.319
....................................
86
Tolerance
Listed
Under
40
CFR
§186.550
....................................
86
Tolerances
Needed
Under
40
CFR
§180.169(
a)
................................
86
CODEX
HARMONIZATION...................................................
89
AGENCY
MEMORANDA
RELEVANT
TO
REREGISTRATION
.....................
94
MASTER
RECORD
IDENTIFICATION
NUMBERS................................
98
O
O
N
H
CH
3
CARBARYL
REREGISTRATION
ELIGIBILITY
DECISION
RESIDUE
CHEMISTRY
CONSIDERATIONS
PC
Code
No.
056801;
Case
0080
INTRODUCTION
Carbaryl
(1
naphthyl
N
methylcarbamate)
is
a
carbamate
insecticide
registered
for
use
on
a
variety
of
field,
fruit,
and
vegetable
crops.
The
reregistration
of
carbaryl
in
the
United
States
is
being
supported
by
the
Aventis
Crop
Science
(basic
producer);
the
Interregional
Research
Project
No.
4
(IR
4)
is
additionally
supporting
the
reregistration
of
carbaryl
use
on
a
few
selected
minor
crops.
Carbaryl
products
are
marketed
under
trade
names
such
as
Sevin®
and
Sevimol®.
Registered
carbaryl
end
use
formulations
include
flowable
concentrates
(FlC),
granulars
(G),
pelleted/
tableted
(P/
T),
ready
to
use
(RTU),
and
wettable
powders
(WP).
Depending
on
the
crop,
these
formulations
may
be
applied
as
dormant,
delayed
dormant,
prebloom,
foliar
(broadcast,
banded,
and
directed
spray),
post
harvest
treatment
(dip),
soil
(broadcast
and
banded),
premise
treatment,
and
direct
animal
treatment
using
ground
or
aerial
equipment.
Carbaryl
may
be
applied
on
agricultural
and
residential
use
sites.
REGULATORY
BACKGROUND
Carbaryl
was
the
subject
of
a
Reregistration
Standard
Guidance
Document
dated
3/
30/
84;
the
Residue
Chemistry
Science
Chapter
of
the
Guidance
Document
was
dated
3/
15/
83.
The
Residue
Chemistry
Chapter
of
the
Carbaryl
(FRSTR)
Reregistration
Standard
was
issued
on
5/
3/
88.
A
Data
Call
In
(DCI)
Notice
for
carbaryl
was
also
issued
4/
91.
These
documents
summarized
the
regulatory
conclusions
based
on
available
residue
chemistry
data,
and
specified
the
additional
data
required
for
reregistration
purposes.
Several
data
submissions
have
been
received
and
evaluated
since
the
FRSTR.
The
information
contained
in
this
document
outlines
the
Residue
Chemistry
Science
Assessments
with
respect
to
the
reregistration
of
carbaryl.
Tolerances
for
residues
of
carbaryl
are
currently
expressed
in
terms
of
carbaryl
(1
naphthyl
Nmethylcarbamate
including
its
hydrolysis
product
1
naphthol,
calculated
as
carbaryl,
for
most
raw
crop
commodities
[40
CFR
§180.169(
a)].
The
established
tolerances
for
residues
in/
on
pineapples,
pome
fruits,
avocados,
and
fresh
dill
are
expressed
in
terms
of
carbaryl
per
se
[40
CFR
§180.169(
d)
and
(e)].
Tolerances
for
residues
in
livestock
commodities
are
expressed
as
2
carbaryl,
including
its
metabolites
1
naphthol
(naphthyl
sulfate),
5,6
dihydrodihydroxy
carbaryl,
and
5,6
dihydrodihydroxy
naphthol,
calculated
as
carbaryl
[40
CFR
§180.169(
b)
and
(c)].
A
tolerance
for
residues
in
pineapple
bran
is
expressed
in
terms
of
carbaryl
per
se
[40
CFR
§186.550].
An
interim
tolerance
has
been
established
for
carbaryl
and
its
1
naphthol
metabolite
in
eggs
[40
CFR
§180.319].
Since
the
FRSTR
was
issued,
the
Agency
has
updated
the
list
of
raw
agricultural
and
processed
commodities
and
feedstuffs
derived
from
crops
(Table
1,
OPPTS
860.1000).
As
a
result
of
changes
to
Table
1,
additional
carbaryl
residue
data
are
now
required
for
some
commodities;
these
data
requirements
have
been
incorporated
into
this
document.
These
new
data
requirements
will
be
imposed
at
the
issuance
of
the
Carbaryl
RED
but
should
not
delay
on
the
reregistration
eligibility
decisions
for
carbaryl.
The
need
for
revisions
to
dietary
exposure/
risk
assessments
will
be
determined
upon
receipt
of
the
required
residue
chemistry
data.
SUMMARY
OF
SCIENCE
FINDINGS
GLN
860.1200:
Directions
for
Use
A
REFS
search,
conducted
on
1/
5/
2000,
identified
15
carbaryl
end
use
products
(EPs)
registered
under
FIFRA
Section
3
to
the
basic
producer,
Aventis
Ag
Company,
with
registered
uses
on
food/
feed
crops.
These
EPs,
including
the
associated
Special
Local
Need
(SLN)
registrations
under
FIFRA
Section
24
(c),
are
listed
in
Table
A1.
3
Table
A1.
Carbaryl
EPs
with
Food/
Feed
Uses
Registered
to
Aventis
Ag
Company.
EPA
Reg.
No.
Label
Acceptance
Date
1
Formulation
Product
Name
234
312
6/
99
10.04%
P/
T
Sevin®
brand
10%
Bait
Carbaryl
Insecticide
264
314
6/
99
50%
WP
Sevin®
brand
50W
Carbaryl
Insecticide
264
315
6/
99
85%
WP
Sevin®
brand
85
Sprayable
Carbaryl
Insecticide
264
316
2
1/
00
80%
WP
Sevin®
brand
80S
Carbaryl
Insecticide
264
320
6/
99
5%
P/
T
Sevin®
brand
5%
Bait
Carbaryl
Insecticide
264
321
6/
99
4
lb/
gal
FlC
Sevimol®
brand
Carbaryl
Insecticide
264
333
2/
01
4
lb/
gal
FlC
Sevin®
brand
XLR
Carbaryl
Insecticide
264
334
2/
99
2
lb/
gal
FlC
Sevin®
brand
RP2
Carbaryl
Insecticide
264
335
10/
00
4
lb/
gal
FlC
Sevin®
brand
RP4
Carbaryl
Insecticide
264
349
3
1/
00
4
lb/
gal
FlC
Sevin®
brand
4F
Carbaryl
Insecticide
264
422
4/
97
4
lb/
gal
RTU
Sevin®
brand
4
Oil
ULV
Carbaryl
Insecticide
264
427
9/
96
3.2
lb/
gal
RTU
Sevin®
brand
4
Oil
41A
Carbaryl
Insecticide
264
429
3/
99
7%
G
Sevin®
brand
Granular
Carbaryl
Insecticide
For
Commercial
Use
Only
264
430
3/
99
6
7%
G
Sevin®
brand
Granular
Carbaryl
Insecticide
For
Outdoor
Home
Use
264
526
4/
00
80%
WP
Sevin®
brand
80
WSP
Carbaryl
Insecticide
1
Date
of
the
most
recently
EPA
approved
label
submitted
by
the
basic
producer
which
corresponds
to
the
most
recently
EPA
approved
label
date
found
in
REFs,
unless
specified
otherwise.
2
Including
SLN
Nos.
CA810059,
FL890036,
and
WA900013.
3
Including
SLN
No.
FL890037.
A
review
of
the
labels
listed
above
and
supporting
residue
data
indicate
that
the
following
label
amendments
are
required:
Based
on
acceptable
residue
data
on
okra
from
IR
4,
the
registrant
should
amend
use
directions
on
FlC
and
WP
labels
to
specify
a
maximum
of
four
applications
per
season
at
1.5
lb
ai/
A/
application
at
a
minimum
retreatment
interval
(RTI)
of
6
days
and
a
minimum
PHI
of
3
days.
Use
directions
for
oysters
on
the
80%
WP
label
(SLN
WA900013)
concerning
the
PHI
should
be
amended
to
read
"treatment
is
allowed
only
on
beds
from
which
no
oysters
will
be
harvested
within
one
year
of
application."
A
comprehensive
summary
of
the
registered
food/
feed
use
patterns
of
carbaryl,
based
on
the
product
labels
registered
to
Aventis,
is
presented
in
Table
A2.
A
tabular
summary
of
the
residue
chemistry
science
assessments
for
reregistration
of
carbaryl
is
presented
in
Table
B.
The
conclusions
listed
in
Table
B
regarding
the
reregistration
eligibility
of
carbaryl
food/
feed
uses
are
based
on
the
use
patterns
registered
by
the
basic
producer,
Aventis.
When
end
use
product
DCIs
are
developed
(e.
g.,
at
issuance
of
the
RED),
all
end
use
product
labels
(e.
g.,
MAI
labels,
SLNs,
4
and
products
subject
to
the
generic
data
exemption)
should
be
amended
such
that
they
are
consistent
with
the
basic
producer's
labels.
GLN
860.1300:
Nature
of
the
Residue
Plants
The
reregistration
requirements
for
plant
metabolism
are
fulfilled.
Acceptable
metabolism
studies
depicting
the
qualitative
nature
of
the
residues
in
lettuce,
radish,
and
soybean
have
been
submitted
and
evaluated.
In
these
studies
(all
conducted
at
1x
rates),
surface
residues
on
radish
tops,
lettuce,
and
soybean
forage
accounted
for
38
67%
of
the
total
radioactive
residues
(TRR),
and
virtually
all
of
these
residues
were
unconjugated
carbaryl.
Unconjugated
carbaryl
ranged
from
36
95%
of
the
TRR
in
all
commodities
of
radish,
lettuce,
and
soybean,
with
the
exception
of
soybean
seed,
in
which
the
parent
accounted
for
only
4%
of
the
TRR.
Other
unconjugated
residues,
including
N(
hydroxymethyl)
carbaryl
(N
OH
Me
carbaryl),
1
naphthol,
and
5,6
dihydro
dihydroxy
1
naphthol,
were
present
in
minor
amounts
(
#
3.4%
of
the
TRR).
Conjugated
carbaryl
accounted
for
#
2.8%
of
the
TRR
in
the
tested
commodities.
Other
conjugates
detected
in
plants
included
a
malonylglycoside
conjugate
of
1
naphthol
comprising
26%
of
the
TRR
in
soybeans;
a
hexose
conjugate
of
N
OH
Me
carbaryl
accounting
for
17%
and
12.2%
of
the
TRR
in
soybeans
and
soybean
hay;
and
several
minor
conjugates
of
desmethyl
carbaryl,
5
hydroxycarbaryl,
and
4
hydroxycarbaryl,
each
at
#
2.7%
of
the
TRR.
Based
on
the
available
metabolism
data,
the
HED
Metabolism
Committee
(S.
Hummel,
2/
8/
96)
determined
that
tolerances
for
crop
commodities
should
be
expressed
as
residues
of
carbaryl
per
se.
The
carbaryl
metabolite,
N
hydroxymethyl
carbaryl
does
not
need
to
be
regulated
because
it
is
expected
to
have
considerably
less
potential
as
a
cholinesterase
inhibitor
(based
on
in
vitro
studies).
As
noted
above,
conjugated
carbaryl
does
not
contribute
significantly
to
the
TRR,
and
is
not
of
concern.
GLN
860.1300:
Nature
of
the
Residue
Livestock
The
reregistration
requirements
for
livestock
metabolism
are
fulfilled.
Acceptable
metabolism
studies
depicting
the
qualitative
nature
of
the
residues
in
ruminants
and
poultry
have
been
submitted
and
evaluated.
The
metabolic
pathways
for
carbaryl
in
plants
and
livestocks
are
similar,
but
are
more
extensive
in
livestocks.
In
the
ruminant
metabolism
study,
lactating
cows
were
orally
dosed
with
1
naphthyl[
14
C]
carbaryl
at
dietary
levels
of
10
100
ppm
for
14
days.
The
high
dose
group
represents
approximately
a
0.8x
feeding
level
based
on
current
tolerance
levels.
The
Metabolism
Assessment
Review
Committee
(6/
17/
99)
concluded
that
tolerances
for
ruminant
meat
and
milk
should
be
expressed
as
residues
of
free
and
conjugated
forms
of
carbaryl,
5,6
dihydro
5,6
dihydroxy
carbaryl,
and
5
methoxy
6
hydroxy
carbaryl.
The
tolerance
expression
should
be
modified
to
reflect
these
changes.
5
Currently,
no
tolerances
are
needed
for
residues
of
carbaryl
in/
on
poultry;
the
presently
registered
uses
of
carbaryl
are
classified
as
Category
3
of
40
CFR
§180.6(
a)
with
respect
to
the
need
for
tolerances
in
poultry
and
eggs
i.
e.,
there
is
no
reasonable
expectation
of
finite
residues.
GLN
860.1340:
Residue
Analytical
Methods
The
available
methods
for
tolerance
enforcement
(PAM,
Volume
II,
Methods
I
through
IV,
A,
and
B)
measure
total
combined
residues
of
carbaryl
and
1
naphthol,
calculated
as
carbaryl.
The
requirement
for
acceptable
enforcement
methods
which
determine
residues
of
carbaryl
per
se
in
plant
and
livestock
commodities
remains
outstanding.
Athough
some
analytical
methods
determine
the
combined
residue
of
carbaryl
and
1
naphthol,
it
should
be
noted
that
1
napthol
is
a
very
minor
part
of
the
residue;
therefore,
the
plant
commodity
tolerances,
which
are
based
on
carbaryl
only,
are
not
greatly
exaggerated.
The
registrant
has
proposed
as
an
enforcement
method
HPLC
Method
CACR
0194,
which
quantifies
carbaryl
per
se
in
plant
matrices.
This
method
has
undergone
successful
independent
laboratory
validation
(ILV)
using
samples
of
representative
plant
commodities
(oily
and
non
oily
matrices),
and
has
also
been
successfully
radiovalidated
using
samples
from
plant
metabolism
studies.
The
method
should
be
submitted
to
the
Agency
for
method
validation.
Residue
data
on
most
crop
plants
and
processed
commodities
have
been
collected
using
the
above
HPLC
method
with
only
minor
modifications
involving
changes
in
solvents
and
cleanup
procedures.
Method
CACR
1212,
a
modification
of
CACR
0194,
has
also
been
used
to
generate
data
on
residues
of
carbaryl
per
se
in
some
of
the
recent
residue
studies.
The
two
methods
are
identical
except
that
with
method
CACR
1212
residues
are
extracted
with
ethyl
acetate
instead
of
DCM,
and
cleanup
procedures
use
deactivated
rather
than
activated
Florisil.
The
carbaryl
HPLCalfalfa
method,
described
in
the
FRSTR,
was
used
to
generate
data
for
earlier
residue
studies.
This
method
does
not
distinguish
between
carbaryl
and
1
naphthol;
however,
the
Agency
concluded
(DP
Barcode
D194407,
S.
Hummel,
2/
25/
94)
that
the
contribution
of
residues
of
1
naphthol
is
insignificant
relative
to
residues
of
carbaryl
per
se.
The
registrant
must
also
propose
an
enforcement
method
for
determining
residues
of
free
and
conjugated
forms
of
carbaryl,
5,6
dihydro
5,6
dihydroxy
carbaryl,
and
5
methoxy
6
hydroxy
carbaryl
in
livestock
commodities.
An
adequate
HPLC
data
collection
method
(Aventis
File
No.
45186)
used
to
determine
residues
of
carbaryl
(free
and
conjugated)
and
its
metabolites
in
livestock
commodities
is
available,
and
has
undergone
a
successful
ILV.
The
method
is
similar
to
method
CARDC
1286
which
was
described
in
a
recent
Agency
review
(C.
Olinger,
12/
13/
99).
Once
the
modified
method
has
been
submitted,
the
Agency
will
initiate
a
method
validation.
GLN
860.1360:
Multiresidue
Methods
The
FDA
PESTDATA
database
indicates
that
residues
of
carbaryl
per
se
are
completely
recovered
using
FDA
Multiresidue
Protocols
A
and
D
(PAM
I
Sections
242.2
and
232.4).
No
data
are
available
concerning
the
recovery
of
carbaryl
by
Protocol
E
(PAM
I
Section
211.1
and
211.2).
These
PAM
I
methods
are
not
expected
to
recover
conjugated
carbaryl
residues.
6
GLN
860.1380:
Storage
Stability
Data
Plants
The
requirements
for
storage
stability
data
are
not
satisfied
for
purposes
of
reregistration.
Additional
data
are
required
depicting
the
storage
stability
of
carbaryl
per
se
in
an
oilseed,
processed
commodities
of
an
oily
crop,
and
a
dried
fruit
stored
for
up
to
10
months.
In
addition,
the
registrant
is
relying
on
earlier
magnitude
of
the
residue
studies
that
are
not
supported
by
the
existing
storage
stability
data;
therefore,
additional
storage
stability
data
are
required.
The
required
data
must
reflect
storage
intervals
of
18
months
for
alfalfa
commodities,
15
months
for
potatoes,
22
months
for
wheat
commodities,
and
33
months
for
rangeland
grass.
In
addition,
if
the
registrant
wishes
to
rely
on
the
previously
submitted
sugar
beet
processing
study,
information
pertaining
to
sample
conditions
and
intervals
for
the
study
must
be
submitted.
Adequate
storage
stability
data
have
been
submitted
indicating
that
residues
of
carbaryl
are
relatively
stable
under
frozen
storage
conditions
(
20
C)
for
up
to
12
months
in/
on
pearled
barley
and
barley
flour,
head
lettuce,
potatoes,
tomatoes
and
tomato
processed
commodities,
and
wheat
forage,
hay,
and
straw.
Residue
decline
was
observed
in
tomato
dry
pomace
after
3
months
storage
(
30
40%),
and
barley
grain
and
peanut
hulls
after
3
months
of
storage
(
50%
and
40%,
respectively;
these
commodities
are
no
longer
considered
to
be
significant
livestock
feed
items.
In
a
separate
study,
carbaryl
residues
were
shown
to
be
stable
in/
on
wheat
grain
stored
at
20
C
for
up
to
7
months.
Adequate
storage
stability
data
have
been
submitted
indicating
that
weathered
residues
of
carbaryl
per
se
are
stable
at
20
C
for
at
least
15
months
in/
on
apple
fruit,
juice,
and
wet
and
dry
pomace;
13
months
in/
on
grapes;
12
months
in/
on
processed
raisins;
11
months
in/
on
almond
nutmeat
and
hulls,
and
dry
bean
hay;
and
10
months
in/
on
dry
bean
vines.
GLN
860.1380:
Storage
Stability
Data
Livestock
For
the
purpose
of
reregistration,
the
requirements
for
storage
stability
data
for
carbaryl
residues
in
livestock
commodities
are
partially
satisfied.
Additional
information
on
the
storage
intervals
prior
to
analysis
for
metabolite
residues
in
the
cattle
feeding
study
is
required.
Samples
from
the
feeding
study
were
analyzed
for
carbaryl
per
se
within
the
interval
of
known
stability
of
free
carbaryl
residues.
The
storage
stability
studies
conducted
to
date
indicate
that
residues
of
unconjugated
carbaryl
and
metabolites
are
less
stable
than
conjugated
residues.
A
storage
stability
study
submitted
in
conjunction
with
the
ruminant
feeding
study
indicated
that
residues
of
carbaryl
per
se
are
relatively
stable
in
frozen
storage
for
up
to
3
months
in
milk,
fat,
and
muscle
and
up
to
1
month
in
kidney.
Residues
of
carbaryl
per
se
in
liver
declined
69%
after
2
weeks
of
storage
and
continued
to
decline
over
the
3
month
storage
interval
(94%
decline).
Tissue
and
milk
samples
from
the
ruminant
feeding
study
were
stored
frozen
for
#
21
days
(9
days
for
liver)
prior
to
carbaryl
analysis.
The
data
indicate
that
conjugated
carbaryl
related
residues
are
relatively
stable
in
frozen
storage
for
up
to
158
days
in
muscle,
173
days
in
liver,
196
days
in
kidney,
215
days
in
fat,
and
7
248
days
in
milk.
A
method
equivalency
study
using
samples
from
the
feeding
study
adequately
demonstrated
that
unconjugated
residues
are
not
a
significant
portion
of
carbaryl
residues
in
liver.
GLN
860.1500:
Crop
Field
Trials
Aventis
CropScience
submitted
data
to
support
the
use
of
granular
(G)
formulations
for
postemergence
applications
to
several
food/
feed
crops.
HED
(DP
Barcode
D240441,
C.
Olinger,
1/
22/
98)
required
the
registrant
to
conduct
one
side
by
side
trial
comparing
a
granular
formulation
and
a
spray
formulation
for
each
crop
group
and
miscellaneous
crop.
To
these
uses,
Aventis
CropScience
submitted
data
comparing
carbaryl
residues
in/
on
asparagus,
cabbage,
sweet
corn,
leaf
lettuce,
black
eyed
peas,
squash,
strawberries,
tomatoes,
and
turnips
following
multiple
applications
of
either
a
4
lb/
gal
flowable
concentrate
(FlC)
or
10%
granular
(G)
formulation
in
side
by
side
tests.
A
total
of
nine
side
by
side
tests
using
a
10%
G
and
4
lb/
gal
FlC
were
conducted
on
crops
representing
major
field
crop
groups
and
miscellaneous
commodities
(asparagus,
cabbage,
sweet
corn,
peas,
squash,
strawberry,
tomato
and
turnip).
The
tests
were
conducted
at
the
maximum
label
rate
specified
on
the
label
for
the
4
lb/
gal
FlC
(EPA
Reg
No.
264
333)
and
were
conducted
in
a
major
growing
region
for
each
crop.
Carbaryl
residues
resulting
from
application
of
the
10%
G
formulation
were
substantially
lower
than
from
the
FlC
formulation
in/
on
9
of
the
14
commodities
analyzed
(asparagus,
cabbage
w/
o
wrapper
leaves,
sweet
corn
forage,
pea
hay
and
dried
seeds,
squash,
strawberries,
tomatoes
and
turnip
tops)
and
were
similar
in
2
other
commodities
(sweet
corn
K+
CWHR
and
fodder).
Although
residues
of
the
10%
G
formulation
were
higher
than
residues
from
the
side
by
side
trial
for
cabbage
(w/
wrapper
leaves)
and
turnip
root,
the
residues
were
similar
or
lower
than
residues
found
in
the
residue
field
trials
submitted
to
the
Agency
in
support
of
tolerances
in/
on
turnip
and
cabbage.
The
data
submitted
are
not
adequate
to
support
the
use
of
granular
(G)
formulations
of
carbaryl
on
leafy
vegetables.
Residues
of
carbaryl
found
in
leaf
lettuce
were
not
consistent.
Both
samples
of
lettuce
from
the
10%
G
treatment
had
substantially
higher
residues
(37.01
and
47.22
ppm)
than
one
of
the
samples
treated
with
the
FlC
(23.25
ppm).
Additionally,
all
residues
were
significantly
above
the
current
tolerance
of
10
ppm.
and
all
residue
data
submitted
in
support
of
the
tolerance
in
lettuce
(<
8.85
ppm).
No
explanation
for
the
higher
residues
was
given
by
the
registrant.
The
registrant
may
elect
to
repeat
the
side
by
side
trial
on
leaf
lettuce
again
or
submit
a
rationale
for
the
results
of
the
leaf
lettuce
study.
In
addition,
conclusions
regarding
the
adequacy
of
the
data
for
alfalfa,
apples,
potatoes,
wheat
processed
commodities,
grasses,
and
soybean
processed
commodities
are
contingent
upon
receipt
and
acceptance
of
adequate
supporting
storage
stability
data.
For
the
purpose
of
reregistration,
adequate
magnitude
of
the
residue
data
are
available
on
the
following
crops:
alfalfa,
almond,
asparagus,
bananas,
beans
(dried
and
succulent),
blueberry,
broccoli,
cabbage,
celery,
cherry,
citrus
fruits,
clover,
corn
(sweet
and
field),
cucurbits
(cantaloupes,
cucumbers
and
squash),
cranberry,
flax,
grape,
okra,
peanut,
peas
(dried
and
8
succulent),
pecan,
pepper,
pistachio,
pome
fruits,
potato,
prickly
pear
cactus,
raspberry,
rice,
sorghum,
soybean,
spinach,
stone
fruits,
strawberry,
sunflower,
sweet
potato,
tobacco,
tomato,
and
walnut.
Adequate
field
trial
data
depicting
carbaryl
residues
following
applications
made
according
to
the
maximum
or
proposed
use
patterns
have
been
submitted
for
these
commodities.
Geographic
representation
is
adequate
and
a
sufficient
number
of
trials
reflecting
representative
formulation
classes
were
conducted.
Carbaryl
residues
were
<LOQ
in/
on
sweet
potato,
sugar
beets,
corn
grain,
flax
seed,
and
peanuts.
Quantifiable
residues
were
detected
in
all
other
RACs.
For
a
given
crop,
residue
levels
were
quite
variable
overall,
probably
owing
to
climactic
variations,
but
were
generally
consistent
within
any
specific
field
trial
location.
In
addition
to
the
required
field
trial
data,
an
adequate
[
14
C]
carbaryl
tobacco
pyrolysis
study
has
been
conducted.
Adequate
data
are
available
to
reassess
the
tolerances
for
residues
of
carbaryl
in/
on
sugar
beet
roots
and
tops
provided
that
use
directions
on
five
currently
approved
labels
are
modified
to
allow
a
maximum
of
two
applications
per
season
at
1.5
lb
ai/
A/
application
and
a
PHI
of
28
days.
The
registrant
has
proposed
(Letter
from
Aventis
to
J.
Loranger,
6/
1/
94)
amending
all
EP
labels
to
conform
to
these
requirements,
and
the
Greybeard
Committee
(1/
9/
97)
has
granted
a
waiver
from
the
requirement
of
additional
field
trials
provided
that
the
labels
are
amended.
Alternatively,
residue
data
are
required
depicting
residues
of
carbaryl
per
se
in/
on
sugar
beet
roots
and
tops
harvested
28
days
following
four
applications
totaling
4.0
lb
ai/
A
(1x
the
maximum
seasonal
rate).
A
total
of
12
tests
should
be
conducted
in
the
following
areas:
Region
5
(5
tests),
Regions
7,
8,
and
9
(one
test
each),
and
Regions
10
and
11
(2
tests
each).
Adequate
residue
data
on
representative
Brassica
and
leafy
vegetables
are
available
to
support
uses
on
other
vegetable
commodities
with
the
same
carbaryl
use
pattern:
Adequate
data
on
broccoli
will
be
translated
to
support
the
uses
on
Brussels
sprouts,
cauliflower,
and
kohlrabi;
data
on
spinach
will
support
tolerances
on
dandelion
and
parsley;
and
residue
data
on
lettuce
will
be
translated
to
endive.
The
available
data
from
alfalfa
will
be
translated
to
support
uses
on
birdsfoot
trefoil.
The
following
data
on
grasses
are
available
for
risk
assessment/
reregistration
purposes:
Residue
data
from
rangeland
grass
field
trials
support
the
current
tolerance
of
100
ppm
in/
on
grass
forage.
Data
on
pasture
hay
harvested
at
the
14
day
PHI
indicate
that
the
tolerance
on
grass
hay
should
be
lowered
to
15
ppm.
The
registrant
has
provided
data
on
pasture
grass
forage
harvested
at
a
PHI
of
14
days.
For
postemergence
applications
to
grasses,
the
Agency
currently
considers
feeding
restrictions
and
PHIs
greater
than
zero
days
impractical
for
forage
of
pasture
and
rangeland
grasses.
Grass
forage
tolerances
are
set
using
residue
data
from
a
0
day
post
treatment
interval.
However,
reasonable
PHIs
are
allowed
for
the
cutting
of
grass
hay.
Adequate
data
are
available
to
reassess
the
tolerances
for
residues
of
carbaryl
in/
on
dried
beans,
cowpeas,
lentils
and
peas
with
pods.
These
data
support
the
establishment
of
crop
subgroup
9
tolerances
for
edible
podded
legume
vegetables
(6A),
and
for
dried,
shelled
pea
and
bean
except
soybean
(6C).
However,
additional
residue
data
are
required
if
the
registrant
seeks
tolerances
for
residues
in/
on
succulent,
shelled
pea
and
bean
commodities.
A
total
of
12
tests,
six
tests
each
on
a
succulent,
shelled
cultivar
of
bean
and
garden
pea,
are
required
to
support
a
tolerance
for
residues
in/
on
the
succulent,
shelled
pea
and
bean
crop
subgroup
(6B).
The
registrant
is
referred
to
OPPTS
GLN
860.1500
for
the
required
number
and
distribution
of
tests.
Data
are
available
to
reassess
the
tolerances
for
residues
in/
on
soybean
forage
and
hay.
To
establish
a
tolerance
for
residues
in/
on
the
foliage
of
legume
vegetables
except
soybeans
crop
subgroup
(7A),
the
guidelines
state
that
three
field
trials
each
are
required
on
any
cultivar
of
bean
and
field
pea.
Although
data
from
forage
and
hay
of
field
pea
are
not
available,
data
from
seven
field
trials
depicting
residues
in/
on
bean
forage
(vines)
and
hay
are
adequate
to
satisfy
the
guidelines
for
a
tolerance
on
the
crop
subgroup
7A.
The
use
patterns
are
the
same
for
forage
and
hay
of
peas
and
beans.
Adequate
data
are
available
to
reassess
the
tolerance
for
wheat
forage
and
straw.
However,
the
Agency
now
considers
wheat
hay
to
be
a
livestock
feed
item.
(OPPTS
GLN
860.1000
Table
1.).
A
full
set
of
20
field
trials
as
specified
in
OPPTS
GLN
860.1500
is
required
depicting
carbaryl
residues
in/
on
wheat
hay.
When
all
the
field
trials
are
complete,
PHIs
and
tolerances
for
hay
based
on
the
field
trial
data
should
be
proposed.
Data
on
wheat
hay
will
be
translatable
to
proso
millet
hay.
The
registrant
intends
to
support
a
tolerance
for
residues
of
carbaryl
in/
on
imported
pineapples
(Aventis
personal
communication
with
C.
Olinger,
9/
24/
98
SMART
meeting).
Residue
data
are
required
depicting
residues
in/
on
pineapples
following
application
of
carbaryl
at
the
maximum
use
rate
and
minimum
PHI.
Five
trials
must
be
submitted,
three
from
Costa
Rica
and
two
from
Mexico.
The
registrant
does
not
intend
to
support
carbaryl
uses
on
avocados,
barley,
maple
sap,
oats,
rye,
and
sweet
sorghum;
however,
IR
4
has
indicated
(Correspondence
from
K.
Dorschner,
IR
4
Project,
9/
15/
94)
that
they
may
fulfill
the
residue
data
requirements
for
some
of
these
commodities.
These
data
have
not
been
submitted.
GLN
860.1520:
Processed
Food/
Feed
Pending
adequate
resolution
of
the
outstanding
storage
stability
issues
noted
above,
the
reregistration
requirements
for
magnitude
of
the
residue
data
in
processed
food/
feed
commodities
are
fulfilled
for
citrus
fruits,
corn,
flaxseed,
grape,
olive,
peanut,
plum,
pome
fruits,
rice,
sorghum,
soybean,
sugar
beet,
sunflower,
potato,
tomato,
and
wheat.
Based
on
the
available
processing
studies,
tolerances
are
required
for
residues
in
citrus
fruit
oil,
raisins,
wet
apple
pomace,
and
rice
hulls
only.
In
a
tomato
processing
study,
carbaryl
residues
concentrated
by
2x
in
puree.
However,
when
this
concentration
factor
is
applied
the
HAFT
residues
of
2.45
ppm
for
tomatoes,
the
resulting
value
is
10
lower
than
the
reassessed
tolerance
(5.0
ppm)
for
residues
in/
on
fruiting
vegetables.
Therefore,
a
separate
tolerance
for
residues
in
puree
is
not
required.
In
an
apple
processing
study,
carbaryl
residues
concentrated
in
wet
apple
pomace
by
1.3x.
Based
on
this
concentration
factor
and
the
current
HAFT
residues
of
10.6
ppm
in/
on
apples,
an
appropriate
tolerance
for
carbaryl
residues
in
wet
apple
pomace
is
15.0
ppm.
Residues
did
not
concentrate
in
apple
juice.
Data
from
the
citrus
fruit
processing
study
indicate
that
residues
of
carbaryl
concentrate
in
citrus
oil
by
2.4x.
Based
on
this
concentration
factor
and
the
current
HAFT
residues
of
8.09
ppm
in/
on
citrus
fruit,
an
appropriate
tolerance
for
carbaryl
residues
in
citrus
oil
is
20.0
ppm.
Residues
did
not
concentrate
in
dried
pulp
or
juice.
Data
from
adequate
grape
processing
studies
indicate
that
residues
of
carbaryl
do
not
concentrate
in
grape
juice;
however,
carbaryl
residues
concentrate
by
1.4x
in
raisins.
Based
on
the
current
HAFT
residues
of
7.94
ppm
in/
on
grapes,
carbaryl
residues
in
raisins
could
be
expected
to
reach
11.1
ppm.
A
12.0
ppm
tolerance
for
carbaryl
residues
in
raisins
should
be
established.
Residues
did
not
concentrate
in
dried
pulp
or
juice.
A
rice
processing
study
indicated
that
residues
of
carbaryl
do
not
concentrate
in
polished
rice
or
bran,
but
concentrate
in
rice
hulls
by
2.4x.
Based
on
this
concentration
factor
and
the
current
HAFT
residues
of
11.0
ppm
in/
on
rice
grain,
residues
in
rice
hulls
could
be
expected
to
reach
26.4
ppm;
therefore,
an
appropriate
tolerance
for
carbaryl
residues
in
rice
hulls
is
30.0
ppm.
Data
from
a
wheat
processing
study
indicate
that
carbaryl
residues
in/
on
wheat
aspirated
grain
fractions
are
11.8x
higher
than
in/
on
wheat
grain.
Based
upon
HAFT
residues
of
0.27
ppm,
residues
of
carbaryl
may
be
expected
to
reach
3.2
ppm
in
wheat
aspirated
grain
fractions.
Adequate
soybean
aspirated
grain
fraction
data
are
available
and
indicate
that
residues
of
carbaryl
in/
on
soybean
aspirated
grain
fractions
are
5.6x
higher
than
in
soybean
seed.
Based
on
HAFT
residues
of
0.15
ppm,
residues
of
carbaryl
may
be
expected
to
reach
0.8
ppm
in
soybean
aspirated
grain
fractions.
For
grain
sorghum,
the
concentration
factor
between
the
aspirated
grain
fractions
and
the
whole
grain
samples
was
7.4x.
Based
on
HAFT
residues
of
9.55
ppm,
residues
of
carbaryl
could
be
expected
to
reach
70.2
ppm
in
sorghum
aspirated
grain
fractions.
As
carbaryl
residues
were
nondetectable
(<
0.02
ppm)
in/
on
all
samples
of
field
corn
grain
from
field
trials
conducted
at
the
maximum
labeled
use
rate
(8.0
lb
ai/
A,
MRID
44058001),
no
carbaryl
residue
data
on
aspirated
grain
fractions
derived
from
field
corn
grain
are
required.
Based
on
these
data,
a
tolerance
of
70
ppm
should
be
established
for
residues
of
carbaryl
per
se
in/
on
aspirated
grain
fractions.
GLN
860.1480:
Meat,
Milk,
Poultry,
Eggs
The
reregistration
data
requirements
for
magnitude
of
the
residue
in
livestock
commodities
are
fulfilled.
11
The
presently
registered
uses
of
carbaryl
are
classified
as
Category
3
of
40
CFR
§180.6(
a)
with
respect
to
the
need
for
tolerances
in
poultry
and
eggs
i.
e.,
there
is
no
reasonable
expectation
of
finite
residues.
Based
upon
the
established
or
reassessed
tolerances
for
carbaryl
residues
in/
on
livestock
feed
items,
the
calculated
maximum
theoretical
dietary
burdens
for
livestock
are
presented
below:
Calculation
of
maximum
dietary
burdens
of
livestock
for
carbaryl.
Feed
Commodity
%
Dry
Matter
a
%
Diet
a
Tolerance
(ppm)
b
Dietary
Contribution
(ppm)
c
Beef
and
Dairy
cattle
grass,
forage
25
60
100.0
240.00
cowpea
seed
88
20
5.0
1.
1
Aspirated
grain
fraction
85
20
70.0
16.0
TOTAL
BURDEN
100
257.1
Swine
sorghum
grain
N/
A
85
10.0
8.
5
cowpea
forage
N/
A
15
60.0
9.
0
TOTAL
BURDEN
100
17.5
a
Table
1
(August
1996).
b
Current
or
reassessed
tolerance
from
Table
C.
c
Contribution
=
[tolerance
/
%
DM
(if
cattle)]
X
%
diet).
An
adequate
ruminant
feeding
study
is
available
reflecting
the
dosing
of
dairy
cattle
for
28
days
at
levels
equivalent
to
114,
342,
and
1140/
570
ppm
in
the
diet
(the
high
dose
level
was
reduced
to
570
ppm
on
Day
5
due
to
toxic
effects
observed
in
study
animals).
These
dosing
levels
represent
0.4x,
1.3x,
and
4.4/
2.2x
the
theoretical
dietary
burden
for
cattle,
and
6.5x,
19.5x,
and
65.1/
32.6x
the
theoretical
dietary
burden
for
swine.
The
calculation
of
the
maximum
dietary
is
tentative
because
data
remain
outstanding
for
pasture
grass
forage.
Based
upon
the
results
of
this
study,
tolerances
for
residues
of
carbaryl
per
se
in
livestock
(excluding
swine)
commodities
should
be
reassessed
as
follows:
1.0
ppm
for
milk,
0.5
ppm
for
fat,
1.0
ppm
for
meat,
and
3.0
ppm
for
meat
byproducts.
Using
the
results
of
the
feeding
study
to
reassess
tolerances
for
swine,
tolerances
for
residues
of
carbaryl
per
se
in
swine
commodities
should
be
reassessed
as
follows:
0.05
ppm
for
fat,
0.1
ppm
for
meat,
and
0.5
ppm
for
meat
byproducts.
GLN
860.1400:
Water,
Fish,
and
Irrigated
Crops
Adequate
residue
data
are
available
to
support
the
use
of
carbaryl
on
oyster
beds
in
WA.
No
residue
data
are
required
for
catfish
or
crayfish
from
the
use
of
carbaryl
on
rice
since
this
use
is
prohibited
on
the
carbaryl
labels.
12
GLN
860.1460:
Food
Handling
Carbaryl
is
presently
not
registered
for
use
in
food
handling
establishments;
therefore,
no
residue
chemistry
data
are
required
under
this
guideline
topic.
GLNs
860.1850
and
860.1900:
Confined/
Field
Accumulation
in
Rotational
Crops
An
adequate
confined
rotational
crop
study
is
available,
and
no
additional
rotational
crop
studies
are
required.
The
current
label
restriction
against
rotating
crops
for
which
carbaryl
is
not
registered
is
adequate.
13
(continued;
footnotes
follow)
Table
A2.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Carbaryl
(Case
0080).
1
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
Food/
Feed
Crop
Uses
Alfalfa
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
Fl/
C
[264
321]
[264
333]
[264
335]
[264
349]
1.5
lb/
A
1
per
cutting
1.5
lb/
A
per
cutting
7
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
14
(continued;
footnotes
follow)
Almond,
chestnut,
filbert,
pecan,
walnut
Foliar,
dormant/
delayed
dormant
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
5.0
lb/
A
4
15.0
lb/
A
14
A
maximum
of
four
applications
may
be
made
(including
dormant/
delayed
dormant
applications)
with
a
minimum
7
day
retreatment
interval.
For
almonds
only,
dormant/
delayed
dormant
applications
may
be
made
in
combination
with
dormant
oil.
Foliar
application
Ground
50%
WP
[CA830007]
80%
WP
[CA830007]
1.0
lb/
100
gal
NS
NS
1
(for
nut
crops)
Use
limited
to
CA
for
nut
crops.
Applications
may
be
made
at
7
day
retreatment
intervals
or
as
needed.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
15
(continued;
footnotes
follow)
Apricot,
cherry,
nectarine,
peach,
plum/
prune
Foliar
and
dormant/
delayed
dormant
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
3.0
lb/
A
4.0
lb/
A
(CA
only)
5.0
lb/
A
(dormant/
delayed
only)
3
(foliar)
and
1
(dormant/
delayed
dormant)
14.0
lb/
A
3
(except
CA)
1
(CA
only)
A
maximum
of
three
foliar
applications
and
one
dormant/
delayed
dormant
application
may
be
made
with
a
minimum
7
day
retreatment
interval
(14
days
in
CA).
A
maximum
seasonal
rate
of
14.0
lb
ai/
A
(5.0
lb
ai/
A
during
dormant/
delayed
dormant
period
and
9.0
lb
ai/
A
during
production
season)
has
been
established.
Foliar
application
Ground
50%
WP
[CA830007]
80%
WP
[CA830007]
1.0
lb/
100
gal
NS
NS
3
Use
limited
to
CA.
Applications
may
be
made
at
7
day
retreatment
intervals
or
as
needed.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
16
(continued;
footnotes
follow)
Asparagus
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
3
6.0
lb/
A
3.0
lb/
A
for
5%
P/
T
only
1
A
maximum
of
three
applications
may
be
made
prior
to
harvest
or
a
maximum
of
five
applications
may
be
made
per
crop
with
a
minimum
3
day
retreatment
interval.
Postharvest
Ground
or
aerial
2
10.0
lb/
A
Not
applicable
(NA)
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
17
(continued;
footnotes
follow)
Asparagus
(continued)
Postharvest
(to
fern
or
brush
growth)
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
4.0
lb/
A
5
10.0
lb/
A
NA
A
maximum
of
five
applications
may
be
made
per
crop
(spears
and
ferns
combined)
with
a
minimum
7
day
retreatment
interval.
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.2
lb/
A
4
NS
1
Use
prohibited
in
CA.
A
maximum
of
four
applications
may
be
made
per
year
with
a
minimum
7
day
retreatment
interval.
Avocado
Foliar
application
Ground
50%
WP
[CA830007]
80%
WP
[CA830007]
1.0
lb/
100
gal
5
NS
5
Use
limited
to
CA.
Applications
may
be
made
at
7
day
retreatment
intervals
or
as
needed.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
18
(continued;
footnotes
follow)
Bean,
cowpea,
pea
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
1.5
lb/
A
4
6.
0
lb/
A
3
A
maximum
of
four
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
Bean,
fresh
and
dried
(Phaseolus
species
including
snap,
navy,
and
kidney),
cowpea,
lentil,
pea,
fresh
and
dried
(pisum
species),
soybean
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
1.5
lb/
A
4
6.
0
lb/
A
3
(fresh
beans)
14
(forage)
21
(dried
beans,
or
hay)
A
maximum
of
four
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
19
(continued;
footnotes
follow)
Beet,
garden,
roots,
carrot,
horseradish,
radish,
parsnip,
rutabaga,
salsify
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
6
6.
0
lb/
A
7
A
maximum
of
six
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.2
lb/
A
4
NS
7
Use
prohibited
in
CA.
A
maximum
of
four
applications
may
be
made
per
year
with
a
minimum
7
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
20
(continued;
footnotes
follow)
Beet,
garden,
tops
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
2.0
lb/
A
5
6.
0
lb/
A
14
A
maximum
of
five
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
Beet,
sugar
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
2.0
lb/
A
4
4.
0
lb/
A
28
(roots
and
forage)
A
maximum
of
four
applications
may
be
made
with
a
minimum
14
day
retreatment
interval.
50%
WP
[264
314]
4
lb/
gal
FlC
[264
321]
[264
335]
1.5
lb/
A
4
4.0
lb/
A
3.0
lb/
A
(FlC)
28
(roots
and
forage)
A
maximum
of
four
applications
may
be
made
with
a
minimum
14
day
retreatment
interval.
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
333]
[264
349]
1.5
lb/
A
2
4.0
lb/
A
3.0
lb/
A
(FlC)
28
(roots
and
forage)
A
maximum
of
two
applications
may
be
made
with
a
minimum
14
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
21
(continued;
footnotes
follow)
Blueberry
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
5
10.0
lb/
A
7
A
maximum
of
five
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
0.05
lb/
1,000
sq.
ft
4
NS
7
Use
prohibited
in
CA.
A
maximum
of
four
applications
may
be
made
per
year
with
a
minimum
7
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
22
(continued;
footnotes
follow)
Broccoli,
Brussels
sprouts,
cabbage,
cauliflower,
Chinese
cabbage,
collards,
kale,
kohlrabi,
mustard
greens
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
4
6.
0
lb/
A
3
14
(Chinese
Cabbage,
collards,
kale
and
mustard
greens)
A
maximum
of
four
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.2
lb/
A
4
NS
3
14
(Chinese
Cabbage,
collards,
kale
and
mustard
greens)
Use
prohibited
in
CA.
A
maximum
of
four
applications
may
be
made
per
year
with
a
minimum
7
day
retreatment
interval.
Brussels
sprouts
(see
broccoli)
Cabbage
(see
broccoli)
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
23
(continued;
footnotes
follow)
Caneberry
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
5
10.0
lb/
A
7
A
maximum
of
five
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.2
lb/
A
4
NS
7
Use
prohibited
in
CA.
A
maximum
of
four
applications
may
be
made
per
year
with
a
minimum
7
day
retreatment
interval.
Carrot
(see
beet,
garden)
Cauliflower
(see
broccoli)
Celery,
dandelion
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
24
(continued;
footnotes
follow)
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
5
6.
0
lb/
A
14
A
maximum
of
five
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.2
lb/
A
4
NS
14
Use
prohibited
in
CA.
A
maximum
of
four
applications
may
be
made
per
year
with
a
minimum
7
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
25
(continued;
footnotes
follow)
Cherry
(see
apricot)
Chestnut
(see
almond)
Chinese
cabbage
(see
broccoli)
Citrus
fruits
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
7.5
lb/
A
8
16.0
lb/
A
5
A
maximum
of
eight
applications
may
be
made
with
a
minimum
14
day
retreatment
interval.
16.0
lb/
A
1
16.0
lb/
A
5
Use
limited
to
CA
for
control
of
California
red
scale
and
yellow
scale.
Foliar
application
Ground
50%
WP
[CA83007]
80%
WP
[CA83007]
1.0
lb/
100
gal
NS
NS
5
Use
limited
to
CA.
Applications
may
be
made
at
7
day
retreatment
intervals
or
as
needed.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
26
(continued;
footnotes
follow)
Citrus
fruits
(continued)
Foliar
application
Ground
or
aerial
80%
WP
[FL890036]
4
lb/
gal
FlC
[FL890037]
10.0
lb/
A
NS
NS
5
Use
limited
to
FL.
Applications
may
be
made
as
a
dilute
or
concentrate
spray
using
ground
equipment
or
in
a
minimum
of
10
gal/
A
by
air.
Applications
may
be
made
as
needed.
Clover
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
1.5
lb/
A
1
per
cutting
1.5
lb/
A
per
cutting
7
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
27
(continued;
footnotes
follow)
Collards
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
4
6.0
lb/
A
6.1
lb/
A
for
the
2
and
4
lb/
gal
FlC
(EPA
Reg.
Nos.
264
334
and
264
335)
14
See
"Broccoli."
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.2
lb/
A
4
NS
14
Use
prohibited
in
CA.
A
maximum
of
four
applications
may
be
made
per
year
with
a
minimum
7
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
28
(continued;
footnotes
follow)
Corn,
field
and
pop
Broadcast
foliar,
banded
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
4
8.
0
lb/
A
14
(forage
and
silage)
48
(grain
and
fodder)
A
maximum
of
four
applications
may
be
made
with
a
minimum
14
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
29
(continued;
footnotes
follow)
Corn,
sweet
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
8
16.0
lb/
A
2
(ears)
14
(forage)
48
(fodder)
A
maximum
of
eight
applications
may
be
made
with
a
minimum
3
day
retreatment
interval.
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.2
lb/
A
4
NS
2
Use
prohibited
in
CA.
A
maximum
of
four
applications
may
be
made
per
year
with
a
minimum
7
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
30
(continued;
footnotes
follow)
Cotton
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
1.5
lb/
A
4
6.
0
lb/
A
14
(forage)
28
(seed)
A
maximum
of
four
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
Band
and/
or
directed
spray
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
1.5
lb/
A
4
6.
0
lb/
A
14
(forage)
28
(seed)
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
31
(continued;
footnotes
follow)
Cowpea
(see
bean)
Cranberry
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
5
10.0
lb/
A
7
See
"Blueberry."
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
32
(continued;
footnotes
follow)
Cucumber,
melon,
pumpkin,
squash
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
1.0
lb/
A
6
6.
0
lb/
A
3
A
maximum
of
six
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
P/
T
formulations
not
used
on
pumpkins
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
33
(continued;
footnotes
follow)
Dandelion
(see
celery)
Eggplant
(see
tomato)
Endive
(see
lettuce)
Filbert
(see
almond)
Flax
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
1.5
lb/
A
2
3.
0
lb/
A
42
(seed
and
straw)
Use
prohibited
in
CA.
A
maximum
of
two
applications
may
be
made
with
a
minimum
14
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
34
(continued;
footnotes
follow)
Grape
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
5
10.0
lb/
A
7
See
"Blueberry."
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.2
lb/
A
4
NS
7
See
"Blueberry."
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
35
(continued;
footnotes
follow)
Grasses
(grown
for
seed)
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
1.5
lb/
A
2
3.
0
lb/
A
14
A
maximum
of
two
applications
may
be
made
with
a
minimum
14
day
retreatment
interval.
Horseradish
(see
beet,
garden)
Kale
(see
broccoli)
Kohlrabi
(see
broccoli)
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
36
(continued;
footnotes
follow)
Lentil
(see
bean)
Lettuce,
head
and
leaf;
endive
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
5
6.
0
lb/
A
14
See
"Beet,
garden,
top"
or
"Celery."
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.2
lb/
A
4
NS
14
See
"Celery."
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
37
(continued;
footnotes
follow)
Melon
(see
cucumber)
Millet,
proso
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
1.5
lb/
A
2
3.
0
lb/
A
7
(forage)
21
(grain
and
straw)
A
maximum
of
two
applications
may
be
made
with
a
minimum
14
day
retreatment
interval.
Use
of
the
50%,
80%,
and
85%
WP
(EPA
Reg.
Nos.
264
314,
264
315,
264
316,
and
264
526)
and
the
4
lb/
gal
FlC
(EPA
Reg.
Nos.
264
321,
264
333,
264
335,
and
264
349)
formulations
is
prohibited
in
CA.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
38
(continued;
footnotes
follow)
Mustard
greens
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
4
6.0
lb/
A
6.1
lb/
A
for
the
2
and
4
lb/
gal
FlC
(EPA
Reg.
Nos.
264
334
and
264
335)
14
See
"Broccoli."
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.2
lb/
A
4
NS
14
A
maximum
of
four
applications
may
be
made
per
year
with
a
minimum
7
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
39
(continued;
footnotes
follow)
Nectarine
(see
apricot)
Olive
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
7.5
lb/
A
2
15.0
lb/
A
14
A
maximum
of
two
applications
may
be
made
with
a
minimum
14
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
40
(continued;
footnotes
follow)
Parsley
(see
lettuce)
Parsnip
(see
beet,
garden)
Pastures
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
1.5
lb/
A
2
3.
0
lb/
A
14
A
maximum
of
two
applications
may
be
made
with
a
minimum
14
day
retreatment
interval.
Cereal
grain
bait
application
Ground
or
aerial
4
lb/
gal
FlC
[264
333]
0.5
lb/
A
1
NS
0
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
41
(continued;
footnotes
follow)
Peach
(see
apricot)
Peanut
Broadcast
foliar,
banded
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
1.0
lb/
A
5
8.
0
lb/
A
14
A
maximum
of
five
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
5
8.
0
lb/
A
14
A
maximum
of
five
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.2
lb/
A
4
NS
14
Use
prohibited
in
CA.
A
maximum
of
four
applications
may
be
made
per
year
with
a
minimum
7
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
42
(continued;
footnotes
follow)
Pea
(see
bean)
Pea,
fresh
and
dried
(Pisum
species)
and
Southern
pea
(see
bean)
Pecan
(see
almond)
Pepper
(see
tomato)
Pistachio
Dormant/
delayed
dormant
and
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
5.0
lb/
A
4
15.0
lb/
A
14
A
maximum
of
four
applications
may
be
made
(including
dormant/
delayed
dormant
applications)
with
a
minimum
7
day
retreatment
interval.
Dormant/
delayed
dormant
applications
may
be
made
in
combination
with
dormant
oil.
Foliar
application
Aerial
80%
WP
[CA810059]
6.0
lb/
A
1
NS
14
Use
limited
to
CA.
Application
may
be
made
in
a
minimum
of
20
gal/
A.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
43
(continued;
footnotes
follow)
Plum/
Prune
(see
apricot)
Pome
fruits
(including
apples,
pears,
loquats,
crabapples,
oriental
pears,
and
quince)
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
3.0
lb/
A
8
15.0
lb/
A
3
A
maximum
of
eight
applications
may
be
made
(including
thinning
sprays
on
apples)
with
a
minimum
14
day
retreatment
interval.
Application
of
the
80%
WP
(EPA
Reg.
Nos.
264
316
and
264
526)
and
4
lb/
gal
FlC
(EPA
Reg.
Nos.
264
333,
264
335,
and
264
349)
formulations
to
quince
are
prohibited.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
44
(continued;
footnotes
follow)
Pome
fruits
(including
apples,
pears,
loquats,
crabapples,
oriental
pears,
and
quince)(
continued)
Postbloom
(for
fruit
thinning)
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
3.0
lb/
A
8
15.0
lb/
A
3
Use
limited
to
apples.
A
maximum
of
eight
applications
may
be
made
(including
thinning
sprays
on
apples)
with
a
minimum
14
day
retreatment
interval.
Postbloom
(for
fruit
thinning)
Ground
4
lb/
gal
FlC
[NC960003]
[OH960003]
[OR950006]
[PA960002]
[VA950001]
[WA940021]
3.0
lb/
A
NS
6.0
lb/
A
for
NC960003
NS
Use
limited
to
NC,
OH,
OR,
PA,
VA,
and
WA.
Applications
may
be
made
after
80
to
100%
petal
fall
and
9
mm
fruit
size.
Postbloom
(for
fruit
thinning)
Ground
50%
WP
[NC820007]
1.0
lb/
100
gal
(dilute)
[250
600
gal
finished
spray/
A]
NS
NS
NS
Tank
mix
use
with
plant
regulator
ethephon
limited
to
NC.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
45
(continued;
footnotes
follow)
Pome
fruits
(including
apples,
pears,
loquats,
crabapples,
oriental
pears,
and
quince)(
continued)
Foliar
application
Ground
50%
WP
[CA83007]
80%
WP
[CA83007]
1.0
lb/
100
gal
5
(for
loquats)
NS
1
(for
apples
and
pears)
5
(for
loquats)
Use
limited
to
CA.
Applications
may
be
made
at
7
day
retreatment
intervals
or
as
needed.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
46
(continued;
footnotes
follow)
Potato
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
6
6.
0
lb/
A
7
See
"Beet,
garden,
roots."
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
47
(continued;
footnotes
follow)
Potato
(continued)
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.2
lb/
A
4
NS
7
See
"Beet,
garden,
roots."
Pumpkin
(see
cucumber)
Radish
(see
beet,
garden)
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
48
(continued;
footnotes
follow)
Rangeland
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
3.2
lb/
gal
RTU
[264
427]
3
4
lb/
gal
RTU
[264
422]
1.0
lb/
A
1
1.
0
lb/
A
0
A
maximum
of
one
application
may
be
made
per
year.
Cereal
grain
bait
application
Ground
or
aerial
4
lb/
gal
FlC
[264
333]
4
lb/
gal
RTU
[264
422]
0.5
lb/
A
1
NS
0
Rhubarb
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
49
(continued;
footnotes
follow)
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.2
lb/
A
4
NS
14
See
"Celery."
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
50
(continued;
footnotes
follow)
Rice
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
1.5
lb/
A
2
4.
0
lb/
A
14
(grain
and
straw)
A
maximum
of
two
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
CA
only:
for
control
of
tadpole
shrimp;
max
number
applications
and
RTI
not
specified.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
51
(continued;
footnotes
follow)
Rutabaga
(see
beet,
garden)
Salsify
(see
beet,
garden)
Sorghum,
grain
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
4
6.
0
lb/
A
21
(grain
and
fodder)
14
(forage
and
silage)
A
maximum
of
four
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
52
(continued;
footnotes
follow)
Soybean
(see
bean)
Spinach
(see
lettuce)
Squash
(see
cucumber)
Strawberry
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
5
10.0
lb/
A
7
A
maximum
of
five
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
53
(continued;
footnotes
follow)
Strawberry
(continued)
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.2
lb/
A
4
NS
7
Use
prohibited
in
CA.
A
maximum
of
four
applications
may
be
made
per
year
with
a
minimum
7
day
retreatment
interval.
Sunflower
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
1.5
lb/
A
2
3.
0
lb/
A
30
(forage)
60
(seed)
Use
in
CA
is
prohibited.
A
maximum
of
two
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
54
(continued;
footnotes
follow)
Sweet
potato
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
8
8.
0
lb/
A
7
A
maximum
of
eight
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
55
(continued;
footnotes
follow)
Sweet
potato
(continued)
Dip
treatment
Preplant
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
8.0
lb/
100
gal
NS
1.
2
lb/
A
NA
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.3
lb/
A
4
NS
7
Use
prohibited
in
CA.
A
maximum
of
four
applications
may
be
made
per
year
with
a
minimum
7
day
retreatment
interval.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
56
(continued;
footnotes
follow)
Swiss
chard
(see
lettuce)
Tobacco
Broadcast
foliar
(plant
bed
and
field)
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
4
8.
0
lb/
A
0
A
maximum
of
four
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
Applications
may
be
made
in
a
minimum
of
10
gal
of
finished
spray/
A.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
57
(continued;
footnotes
follow)
Tomato,
pepper,
eggplant
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
2
lb/
gal
FlC
[264
334]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
2.0
lb/
A
7
8.
0
lb/
A
3
A
maximum
of
seven
applications
may
be
made
with
a
minimum
7
day
retreatment
interval.
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.2
lb/
A
4
NS
3
Use
prohibited
in
CA.
A
maximum
of
4
applications
may
be
made
per
year
with
a
minimum
7
day
RTI.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
58
(continued;
footnotes
follow)
Trefoil,
birdsfoot
Broadcast
foliar
Ground
or
aerial
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
1.5
lb/
A
1
per
cutting
1.5
lb/
A
per
cutting
7
Turnip,
roots
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
2.0
lb/
A
6
6.
0
lb/
A
7
See
"Beet,
garden,
roots."
Soil
broadcast
Before,
during,
or
after
the
growing
season
Ground
7%
G
[264
429]
[264
430]
2.2
lb/
A
4
NS
7
See
"Beet,
garden,
root."
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
59
(continued;
footnotes
follow)
Turnip,
tops
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
2.0
lb/
A
5
6.
0
lb/
A
14
See
"Beet,
garden,
top."
Walnut
(see
almond)
Wheat
Broadcast
foliar
Ground
or
aerial
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
1.5
lb/
A
2
3.
0
lb/
A
7
(forage)
21
(grain
and
straw)
A
maximum
of
two
applications
may
be
made
with
a
minimum
14
day
retreatment
interval.
Use
of
the
50%,
80%,
and
85%
WP
(EPA
Reg.
Nos.
264
314,
264
315,
264
316,
and
264
526)
and
4
lb/
gal
FlC
(EPA
Reg.
Nos.
264
321,
264
333,
264
335,
and
264
349)
formulations
is
prohibited
in
CA.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
60
(continued;
footnotes
follow)
Livestock
Uses
Poultry
treatment
(chickens,
ducks,
geese,
game
birds,
pigeons,
and
turkeys)
Direct
animal
treatment
Electric
fog
machine
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
349]
5
oz/
1
gal
[1.
5
gal
finished
spray
per
1,000
hens]
NS
NS
7
day
pre
slaughter
interval
Applications
may
be
repeated
in
4
weeks
if
necessary.
Direct
animal
treatment
Compressed
air
sprayer
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
333]
[264
335]
[264
349]
3.2
oz/
5
gal
[1
gal
finished
spray
per
100
hens]
NS
NS
7
day
pre
slaughter
interval
Applications
may
be
repeated
in
4
weeks
if
necessary.
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
61
(continued;
footnotes
follow)
Poultry
houses
(chickens,
ducks,
geese,
gamebirds,
pigeons,
and
turkeys)
Premise
treatment
Spreader
or
sprayer
5%
P/
T
[264
320]
10.04%
P/
T
[264
312]
2.4
oz/
1,000
sq.
ft
NS
NS
NA
Applications
may
be
made
uniformly
to
the
floor
or
litter
area.
A
7
day
preslaughter
interval
(PSI)
has
been
established
for
poultry,
game
birds
and
their
premises.
50%
WP
[264
314]
80%
WP
[264
316]
[264
526]
85%
WP
[264
315]
4
lb/
gal
FlC
[264
321]
[264
335]
[246
349]
4
50
lb/
100
gal
[1
2
gal
of
spray
mixture
per
1,000
sq.
ft]
NS
NS
NA
Applications
may
be
made
to
the
wall,
litter,
or
roost
area.
A
7
day
PSI
has
been
established
for
birds
and
their
premises.
Premise
treatment
Sprayer
or
duster
80%
WP
[264
316]
[264
526]
1.0
lb/
1,000
sq.
ft
NS
NS
NA
Applications
may
be
made
as
a
dilute
spray
or
as
a
dry
dust
to
floor
surface,
walls,
cracks,
posts,
and
crevices.
A
7
day
PSI
has
been
established
for
birds
and
their
premises.
4
lb/
gal
FlC
[264
333]
[264
335]
[264
349]
0.54
0.55
lb/
1,000
sq.
ft
NS
NS
NA
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Maximum
Single
Application
Rate,
ai
Maximum
Number
of
Applications
Per
Season
Maximum
Seasonal
Rate,
ai
Preharvest
Interval,
Days
Use
Directions
and
Limitations
2
62
Fish
and
Shellfish
Uses
Oyster
beds
Application
to
dewatered
oyster
beds
Ground
or
aerial
80%
WP
[WA900013]
10.0
lb/
A
NS
NS
365
Application
is
for
control
of
ghost
shrimp
and
mud
shrimp.
Application
must
be
made
and
completed
within
30
minutes
after
low
tide
to
prevent
direct
contamination
of
water.
Use
is
limited
to
areas
greater
than
200
feet
from
channels
and
sloughs.
For
aerial
application,
a
200
foot
buffer
zone
is
required
between
the
treatment
area
and
the
nearest
shellfish
to
be
harvested.
A
50
foot
buffer
zone
is
required
if
treatment
is
by
hand
spray.
Treatment
is
allowed
only
on
ground
with
no
oysters
within
one
year
of
harvest
are
present.
1
The
following
labels
list
a
drench
spot
application
to
fire
ant
mounds
in
rangeland
or
pastures:
Epa
Reg.
Nos.
264
314,
315,
316,
321,
349,
and
526.
EPA
Reg.
Nos.
264
334
and
335
permit
drench
spot
treatment
for
fire
ants
on
all
labeled
crops/
sites.
The
labeled
rate
for
fire
ant
spot
treatment
is
6.7
10.6
g/
gal.
Granular
spot
treatment
with
EPA
Reg.
Nos.
264
429
and
430
may
also
be
made
at
6g/
ant
mound.
2
A
restriction
against
planting
rotational
food
and
feed
crops
not
listed
on
the
label
or
other
carbaryl
labels
in
carbaryl
treated
soil
is
specified
on
the
labels
for
the
following
products:
EPA
Reg.
Nos.
264
312,
264
314,
264
315,
264
316,
264
320,
264
321,
264
333,
264
334,
264
335,
264
349,
264
422,
264
427,
264
429,
and
264
526.
Irrigation
restrictions:
(i)
Use
in
irrigation
systems
prohibited
for
EPA
Reg.
No.
264
422,
427;
(ii)
use
of
reclaimed
irrigation
water
on
upland
crops
for
which
no
carbaryl
tolerances
established
prohibited
for
EPA
Reg.
Nos.
264
312,
314,
315,
320,
321,
333,
334,
335,
349,
422,
427;
(iii)
may
be
applied
through
sprinkler
irrigation
systems
including
center
pivot
and
solid
set
use
of
all
other
types
prohibited
EPA
Reg.
Nos.
264
312,
314,
315,
316,
321,
333,
349,
526).
12
Hour
RTI
for
EPA
Reg.
Nos.
264
312,
314,
315,
316,
320,
321,
333,
335,
349,
422,
427,
526).
3
The
3.2
lb/
gal
RTU
(EPA
Reg.
No.
264
427)
product
label
lists
the
application
rates
in
quarts
of
product
per
acre
for
non
cropland
and
rangeland;
however,
to
make
this
product
label
consistent
with
the
other
products
the
application
rates
should
be
expressed
as
fluid
ounces
per
acre.
(continued;
footnotes
follow)
63
Table
B.
Residue
Chemistry
Science
Assessments
for
Reregistration
of
Carbaryl.
GLN:
Data
Requirements
Current
Tolerances,
ppm
[40
CFR]
Must
Additional
Data
Be
Submitted?
1
References
2
860.1200:
Directions
for
Use
N/
A
=
Not
Applicable
Yes
3
860.1300:
Plant
Metabolism
N/
A
No
00049135
00053897
00116083
00118342
00124353
00124968
00125170
43249101
4
43249102
4
43249103
4
860.1300:
Livestock
Metabolism
N/
A
No
5
00015669
00053897
00080417
00080679
00080680
00080681
00080682
00080683
00080686
00080689
00080690
00091952
00095927
00118346
00118347
00118365
00118368
00118371
00118375
00118376
00118377
00139664
43324601
6,7
860.1340:
Residue
Analytical
Methods
Plant
commodities
N/
A
Yes
8
00080417
00080680
00098504
00107017
00118342
00118346
00118366
00118367
00118368
00118370
00118372
00118373
00118377
00124334
00124361
00145884
00147760
00154626
00156736
00159326
05001852
05004154
05004934
05008728
05010424
05014156
05014889
05016141
05018884
05019959
40255702
40408601
43672701
9
43672702
9
43786805
10
44155401
11
Livestock
commodities
N/
A
Yes
12
00061103
00080417
00080680
00118346
00118366
00118367
00118368
00118370
00118372
00118373
00118375
00118376
05001852
05004154
05008728
05010424
05014156
05014889
05016141
05018884
05019959
44286901
13
44286902
13
44286903
13
860.1360:
Multiresidue
Methods
N/
A
No
860.1380:
Storage
Stability
Data
Plant
commodities
N/
A
Yes
14
00163007
00163009
00163014
40408601
43850902
15
44068401
16
44123101
17
44250301
16
44412501
18
Table
B
(continued).
GLN:
Data
Requirements
Current
Tolerances,
ppm
[40
CFR]
Must
Additional
Data
Be
Submitted?
1
References
2
(continued;
footnotes
follow)
64
Livestock
commodities
N/
A
No
44250901
13
44381901
13
860.1500:
Crop
Field
Trials
Root
and
Tuber
Vegetables
Group
Beet,
garden,
roots
5
[§
180.169(
a)]
No
00089868
43813601
10
Beet,
sugar,
roots
None
established
No
00089868
00163007
40376001
19
40376002
20
Carrot
10
[§
180.169(
a)]
No
00090325
43813601
10
Horseradish
5
[§
180.169(
a)]
No
00089868
43813601
10
Parsnips
5
[§
180.169(
a)]
No
00089868
43813601
10
Potato
0.
2
[§
180.169(
a)]
No
00107017
00134421
40512501
20
Radishes
5
[§
180.169(
a)]
No
00089868
43813601
10
Salsify,
roots
5
[§
180.169(
a)]
No
00089868
43813601
10
Turnip,
roots
5
[§
180.169(
a)]
No
00089868
43813601
10
Sweet
potato
0.2
[§
180.169(
a)]
No
00107017
43702002
21
Leaves
of
Root
and
Tuber
Vegetables
Group
Beet,
garden,
tops
12
[§
180.169(
a)]
No
00089868
43813601
10
Beet,
sugar,
tops
100
[§
180.169(
a)]
No
19
00089868
Salsify,
tops
10
[§
180.169(
a)]
No
00089868
43813601
10
Turnip,
tops
12
[§
180.169(
a)]
No
00089868
43813601
10
Leafy
Vegetables
(except
Brassica)
Vegetables
Group
Celery
10
[§
180.169(
a)]
No
00124337
43677401
22
Dandelions
12
[§
180.169(
a)]
No
22
00089868
43677401
22
Endive
10
[§
180.169(
a)]
No
23
00089868
43677401
22
Table
B
(continued).
GLN:
Data
Requirements
Current
Tolerances,
ppm
[40
CFR]
Must
Additional
Data
Be
Submitted?
1
References
2
(continued;
footnotes
follow)
65
Lettuce
10
[§
180.169(
a)]
No
00089868
00090162
43677401
22
Parsley
12
[§
180.169(
a)]
No
23
00089868
43677401
22
Spinach
12
[§
180.169(
a)]
No
00089868
43677401
22,24
Swiss
chard
12
[§
180.169(
a)]
No
00089868
43677401
22
Brassica
(Cole)
Vegetables
Group
Broccoli
10
[§
180.169(
a)]
No
00090325
43721001
22
44019701
25
Brussels
sprouts
10
[§
180.169(
a)]
No
26
00090325
43721001
22
Cabbage
10
[§
180.169(
a)]
No
00090325
43786806
10
Cauliflower
10
[§
180.169(
a)]
No
27
00090325
43721001
22
Chinese
cabbage
10
[§
180.169(
a)]
No
00089868
43794903
10
Collards
12
[§
180.169(
a)]
No
00089868
43794903
10
Kale
12
[§
180.169(
a)]
No
00089868
43794903
10
Kohlrabi
10
[§
180.169(
a)]
No
27
00090325
43721001
22
Mustard
greens
12
[§
180.169(
a)]
No
00089868
43794903
10
Legume
Vegetables
Group
Bean,
fresh
and
dried
10
[§
180.169(
a)]
No
00089679
00089680
00089681
00082424
00089837
00090113
00163014
00124334
43786804
10
43984701
27
Cowpeas
5
[§
180.169(
a)]
No
00089837
43694103
22
Lentils
10
[§
180.169(
a)]
No
00089837
00124334
43694103
22
Peas
(with
pods)
10
[§
180.169(
a)]
No
00090113
00124334
43703102
22
Soybeans
5
[§
180.169(
a)]
No
00089837
43694102
22
Foliage
of
Legume
Vegetables
Group
Table
B
(continued).
GLN:
Data
Requirements
Current
Tolerances,
ppm
[40
CFR]
Must
Additional
Data
Be
Submitted?
1
References
2
(continued;
footnotes
follow)
66
Bean,
forage
and
hay
100,
forage
100,
hay
[§
180.169(
a)]
No
28
00082424
00089679
00089680
00089681
00089837
00125090
Cowpea,
forage
and
hay
100,
forage
100,
hay
[§
180.169(
a)]
No
00089837
43786804
10
Pea,
vines
100
[§
180.169(
a)]
No
00089837
00124334
43786804
10
Soybean,
forage
and
hay
100,
forage
100,
hay
[§
180.169(
a)]
No
00089837
43694102
22
Fruiting
Vegetables
(Except
Cucurbits)
Group
Eggplant
10
[§
180.169(
a)]
No
00089600
43686701
22
43996101
28
Pepper
10
[§
180.169(
a)]
No
00089600
43686701
22
Tomato
10
[§
180.169(
a)]
No
00089600
00159326
43996101
28
Cucurbit
Vegetables
Group
Cucumber
10
[§
180.169(
a)]
No
00089376
43786802
10
Melon
10
[§
180.169(
a)]
No
00090325
43786802
10
Pumpkin
10
[§
180.169(
a)]
No
00090325
43786802
10
Squash,
summer
10
[§
180.169(
a)]
No
00089376
43786802
10
Squash,
winter
10
[§
180.169(
a)]
No
00090325
43786802
10
Citrus
Fruits
Group
Citrus
10
[§
180.169(
a)]
No
00090204
00090320
00163008
43802101
15
44211801
29
Pome
Fruits
Group
Pome
fruits
10
[§
180.169(
d)]
No
00080419
00082420
00082423
00083311
00083312
00089455
00089679
00089680
00159327
44072901
11
Stone
Fruits
Group
Apricot
10
[§
180.169(
a)]
No
00090160
43793202
15
44284701
30
Table
B
(continued).
GLN:
Data
Requirements
Current
Tolerances,
ppm
[40
CFR]
Must
Additional
Data
Be
Submitted?
1
References
2
(continued;
footnotes
follow)
67
Cherry
10
[§
180.169(
a)]
No
00089348
00124345
43793202
15
44284701
30
Nectarine
10
[§
180.169(
a)]
No
00090160
43793202
15
44284701
30
Peach
10
[§
180.169(
a)]
No
00082422
43793202
15
44284701
30
Plum
(fresh
prune)
10
[§
180.169(
a)]
No
00089348
00124345
43793202
15
44284701
30
Berries
Group
Blackberry
12
[§
180.169(
a)]
No
00089868
43698201
22
Blueberry
10
[§
180.169(
a)]
No
00090161
43694101
22
Boysenberry
12
[§
180.169(
a)]
No
00089868
43698201
22
Dewberry
12
[§
180.169(
a)]
No
00089868
43698201
22
Loganberry
12
[§
180.169(
a)]
No
00089868
43698201
22
Raspberry
12
[§
180.169(
a)]
No
00089868
43698201
22
Tree
Nuts
Group
Almond,
nutmeat
and
hulls
1,
almonds;
40,
almonds,
hulls
[§
180.169(
a)]
No
00108985
00140447
43786801
15
Chestnut
1
[§
180.169(
a)]
No
43786801
15
43802102
15
Filbert
1
[§
180.169(
a)]
No
00090156
43786801
15
43802102
15
Pecan
1
[§
180.169(
a)]
No
00123219
43802102
15
Walnut
1
[§
180.169(
a)]
No
00108985
00140447
43818901
15
Cereal
Grains
Group
Barley,
grain
0
[§
180.169(
a)]
No
30
Corn,
field
and
pop
5,
fresh
(including
sweet)
K+
CWHR
[§
180.169(
a)]
No
00089420
00125090
00125107
00163009
44058001
16
Table
B
(continued).
GLN:
Data
Requirements
Current
Tolerances,
ppm
[40
CFR]
Must
Additional
Data
Be
Submitted?
1
References
2
(continued;
footnotes
follow)
68
Corn,
sweet
5,
fresh
(including
sweet)
K+
CWHR
[§
180.169(
a)]
No
00089378
00089420
00125090
00125107
44058101
11
Millet,
proso,
grain
3
[§
180.169(
a)]
No
31
00074368
43975601
15
Oats,
grain
0
[§
180.169(
a)]
No
30
Rice,
grain
5
[§
180.169(
a)]
No
00089837
00125138
43802103
15
Rye,
grain
0
[§
180.169(
a)]
No
30
Sorghum,
grain
10
[§
180.169(
a)]
No
43794901
10
Wheat,
grain
3
[§
180.169(
a)]
No
00015669
00115284
00136415
41594301
32
43975601
15
Forage,
Fodder,
and
Straw
of
Cereal
Grains
Group
Barley,
forage
and
straw
100,
green
fodder
100,
straw
[§
180.169(
a)]
No
30
Corn,
fodder
and
forage
100,
fodder
100,
forage
[§
180.169(
a)]
No
00089378
00089420
00125090
00125107
44058001
33
44058101
11
Millet,
proso,
straw
100
[§
180.169(
a)]
No
31
00074368
43975601
15
Oats,
forage
and
straw
100,
green
fodder
100,
straw
[§
180.169(
a)]
No
30
Rice,
straw
100,
straw
[§
180.169(
a)]
No
00089837
00125138
43802103
15
Rye,
forage
100,
green
fodder
100,
straw
[§
180.169(
a)]
No
30
Sorghum,
forage
100,
forage
[§
180.169(
a)]
No
00159329
43794901
10
Wheat,
forage
and
straw
100,
green
fodder
100,
straw
[§
180.169(
a)]
Yes
34
00015669
00115284
00136415
Grass
Forage,
Fodder,
and
Hay
Group
Pastures
100,
grass;
100,
hay
[§
180.169(
a)]
Yes
35
00089837
00125121
00125123
00125555
00163006
43716601
22
Rangeland
100,
grass;
100,
hay
[§
180.169(
a)]
No
00089837
00125121
00125123
00125555
00163006
44065901
34
Table
B
(continued).
GLN:
Data
Requirements
Current
Tolerances,
ppm
[40
CFR]
Must
Additional
Data
Be
Submitted?
1
References
2
(continued;
footnotes
follow)
69
Non
grass
Livestock
Feeds
(Forage,
Fodder,
Straw,
and
Hay)
Group
Alfalfa,
forage
and
hay
100,
fresh;
100,
hay
[§
180.169(
a)]
No
00089837
00125121
00125123
00159325
Birdsfoot
trefoil,
forage
and
hay
100,
fresh;
100,
hay
[§
180.169(
a)]
No
00089837
00125121
00125123
00159325
Clover,
forage
and
hay
100,
fresh;
100,
hay
[§
180.169(
a)]
No
00089837
00125121
00125123
43694105
22
Herbs
and
Spices
Group
Dill,
fresh
0.2
[§
180.169(
e)]
No
PP#
7E3543
36
Miscellaneous
Commodities
Aspirated
grain
fractions
None
No
37
43794902
10
43813602
10
Asparagus
10
[§
180.169(
a)]
No
00083527
00140449
43654201
10
Avocado
10
[§
180.169(
e)]
No
30
Banana
10
[§
180.169(
a)]
No
44798401
39
Cranberry
10
[§
180.169(
a)]
No
00090161
43697604
22
Cotton,
seed
and
forage
5,
cottonseed
100,
cotton
forage
[§
180.169(
a)]
No
(Revoke)
38
00089837
00124343
00125099
40881307
Flax,
seed
and
straw
5,
seed;
100,
straw
[§
180.169(
a)]
No
00074366
00074367
43982801
15
Grapes
10
[§
180.169(
a)]
No
00089418
00089458
00125084
43793201
15
Maple,
sap
0.5
[§
180.169(
a)]
No
30
Okra
10
[§
180.169(
a)]
No
00090229
44123101
17
Olives
10
[§
180.169(
a)]
No
40
00090281
43702001
22
44321301
18
Peanuts,
nut
and
hay
5,
peanut;
100,
hay
[§
180.169(
a)]
No
00089837
43703101
22
Pineapple
2.
0
[§
180.169(
d)]
Yes
39
PP#
5F3208
Pistachio
nuts
1
[§
180.169(
a)]
No
00124335
43703103
22
Prickly
pear
cactus
12,
fruit;
12,
pads
[§
180.169(
a)]
No
00103288
44145201
17
Table
B
(continued).
GLN:
Data
Requirements
Current
Tolerances,
ppm
[40
CFR]
Must
Additional
Data
Be
Submitted?
1
References
2
(continued;
footnotes
follow)
70
Strawberry
10
[§
180.169(
a)]
No
00089348
43698202
22
Sunflower
1,
seeds
[§
180.169(
a)]
No
00058927
00058928
43786803
10
Tobacco
None
established
No
44114301
40
860.1520:
Processed
Food/
Feed
Beet,
sugar
None
established
No
00163017
Citrus
fruits
None
established
No
43694104
22
Corn,
field
None
established
No
00163018
43915201
15
Cottonseed
None
established
No
43850901
15
Flaxseed
None
established
No
00074366
00074367
Grapes
None
established
No
00163010
00163011
43697601
22
43697602
22
Olives
None
established
No
43698203
22
Peanut
None
established
No
00163012
44046101
26
Pineapple
20,
bran
[§
186.550]
No
PP#
5F3208
41
Plum
None
established
No
00159328
Pome
fruits
None
established
No
43702003
22
Potato
None
established
No
00159324
43697603
22
Rice
None
established
No
00163013
43813603
10
Sorghum
None
established
No
00163015
43813604
10
Soybean
None
established
No
00163016
43794902
10
Sunflower
None
established
No
43845205
15
Tomato
None
established
No
43686702
22
Wheat
None
established
No
43813602
10
860.1480:
Meat,
Milk,
Poultry,
Eggs
Milk
and
the
Fat,
Meat,
and
Meat
Byproducts
of
Cattle,
Goats,
Hogs,
Horses,
and
Sheep
0.1,
fat,
meat,
and
meat
byproducts;
1,
kidney
and
liver
[§
180.169(
b)]
No
00015669
00061106
00080417
00080419
00080420
00089380
00089836
00089837
00118342
00118346
00118367
00118368
00118370
00118372
00118373
00118374
00118378
40881302
40881312
40881313
40881314
44250901
13
44381901
13
Table
B
(continued).
GLN:
Data
Requirements
Current
Tolerances,
ppm
[40
CFR]
Must
Additional
Data
Be
Submitted?
1
References
2
(continued;
footnotes
follow)
71
Fat,
Meat,
and
Meat
Byproducts
of
Poultry
5.0
Fat
and
meat
[§
180.169(
b)]
No
00061103
00080420
00080680
00118375
00118376
00124367
00125571
00135678
00135680
40881308
40881309
Eggs
0.5
[§
180.319]
No
Table
B
(continued).
GLN:
Data
Requirements
Current
Tolerances,
ppm
[40
CFR]
Must
Additional
Data
Be
Submitted?
1
References
2
72
1.
Reassessed
tolerances
for
leafy
vegetables
remain
tentative
until
granular
data
required
to
support
the
reregistration
of
carbaryl
are
submitted.
The
registrant
should
conduct
one
side
by
side
trial
comparing
a
granular
formulation
and
a
spray
formulation.
If
the
residues
resulting
from
use
of
the
granular
formulation
for
all
crops
are
the
same
or
less
than
the
spray
formulation,
then
no
additional
granular
data
would
be
required.
2.
Bolded
references
were
reviewed
in
the
Residue
Chemistry
Chapter
of
the
Carbaryl
Reregistration
Standard
dated
3/
15/
83
or
the
Interim
Residue
Chemistry
Chapter
of
the
Carbaryl
Reregistration
Standard
dated
3/
30/
84.
Italicized
references
were
reviewed
in
the
Residue
Chemistry
Chapter
of
the
Carbaryl
(FRSTR)
Reregistration
Standard
dated
5/
3/
88.
All
other
references
were
reviewed
as
noted.
3.
Label
revisions
are
required
for
several
crops
in
order
to
reflect
the
parameters
of
use
patterns
for
which
residue
data
are
available.
Details
of
the
required
label
amendments
are
presented
in
the
Directions
for
Use
section.
4.
DP
Barcode
D204197,
11/
28/
95,
S.
Hummel.
5.
No
tolerances
are
needed
for
residues
of
carbaryl
in/
on
poultry;
the
presently
registered
uses
of
carbaryl
are
classified
as
Category
3
of
40
CFR
§180.6(
a)
with
respect
to
the
need
for
tolerances
in
poultry
and
eggs
i.
e.,
there
is
no
reasonable
expectation
of
finite
residues.
6.
CB
No.
14249,
DP
Barcode
D206777,
11/
28/
95,
S.
Hummel.
7.
DP
Barcode
D255855,
C.
Olinger,
5/
16/
99
and
6/
17/
99.
8.
The
proposed
HPLC
enforcement
method
for
carbaryl
per
se
in
plants
(Method
CACR
0194)
should
be
submitted
to
the
Agency
for
validation.
9.
DP
Barcode
D216544,
S.
Hummel,
1/
22/
96.
10.
DP
Barcodes
D216242,
D219527,
D219596,
and
D220287,
T.
Morton,
9/
17/
98.
11.
DP
Barcodes
D230246,
D230406,
and
D231533,
M.
Perry,
5/
26/
98.
12.
HPLC
Method
Aventis
File
No.
45186,
which
has
successfully
undergone
an
ILV
should
be
submitted
to
the
Agency
for
validation
13.
DP
Barcodes
D236574,
D236421,
and
D240469,
C.
Olinger,
12/
15/
99.
860.1400:
Water,
Fish,
and
Irrigated.
Crops
Oysters
0.25
[§
180.169(
a)]
No
PP#
1E2554
42
860.1460:
Food
Handling
Establishments
N/
A
N/
A
860.1850:
Confined
Rotational
Crops
N/
A
No
43651701
43
860.1900:
Field
Rotational
Crops
None
established
No
Table
B
(continued).
73
14.
Additional
data
are
required
depicting
the
storage
stability
of
carbaryl
per
se
in
processed
commodities
of
an
oily
crop
for
up
to
10
months.
The
maximum
storage
interval
for
processed
commodities
of
an
oily
crop
was
10
months
(soybean
processed
commodities).
In
addition,
the
registrant
is
relying
on
earlier
magnitude
of
the
residue
studies
which
are
not
supported
by
the
existing
storage
stability
data.
Unless
the
registrant
can
demonstrate
that
samples
from
studies
reflecting
the
use
patterns
the
registrant
wishes
to
support
were
not
stored
longer
than
12
months,
additional
storage
stability
data
are
required.
The
required
data
must
reflect
storage
intervals
of
18
months
for
alfalfa
commodities,
15
months
for
potatoes,
22
months
for
wheat
commodities,
and
33
months
for
rangeland
grass.
In
addition,
if
the
registrant
wishes
to
rely
on
the
previously
submitted
sugar
beet
processing
study,
information
pertaining
to
sample
conditions
and
intervals
for
the
study
must
be
submitted.
15.
DP
Barcodes
D218865,
D219999,
D220949,
D221158,
D223008,
D219971,
D220601,
D220948,
D221313,
D225204,
and
D225576,
F.
Suhre,
9/
13/
96.
16.
DP
Barcodes
D228656
and
D235113,
C.
Olinger,
11/
09/
99.
17.
DP
Barcodes
D230900
and
D231134,
M.
Perry,
5/
22/
98
18.
DP
Barcode
D240998
and
D237653,
C.
Olinger,
4/
9/
98.
19.
CB
No.:
3027,
DP
Barcode:
none,
M.
Nelson,
3/
28/
88.
20.
CB
No.:
3510,
DP
Barcode:
none,
M.
Kovacs,
4/
25/
88.
21.
DP
Barcodes
D217179,
D217172,
D217177,
D217631,
D217704,
and
D217705,
F.
Suhre,
10/
7/
96.
22.
Data
for
spinach
will
be
translated
to
dandelion
and
parsley.
23.
Data
on
lettuce
will
translate
to
endive.
24.
DP
Barcode
D234692,
C.
Olinger,
9/
11/
97.
25.
DP
Barcodes
D227765
and
D227009,
M.
Perry,
5/
12/
98.
26.
Data
on
broccoli
will
be
translated
to
Brussels
sprouts,
cauliflower,
and
kohlrabi.
27.
DP
Barcodes
D225659
and
D226582,
F.
Suhre,
8/
21/
96.
28.
Data
are
no
longer
required
as
cowpea
is
the
only
bean
crop
considered
for
livestock
feeding.
29.
DP
Barcodes
D236422
and
D236485,
C.
Olinger,
11/
9/
99.
30.
The
registrant
does
not
intend
to
support
carbaryl
uses
on
avocados,
barley,
maple
trees,
oats,
rye,
and
sweet
sorghum;
however,
IR
4
has
indicated
(Correspondence
from
K.
Dorschner,
IR
4
Project,
9/
15/
94)
that
they
may
submit
residue
data
to
support
reregistration
for
some
of
these
commodities.
These
data
have
not
been
submitted.
31.
Acceptable
residue
data
on
wheat
will
be
translated
to
support
the
use
on
proso
millet.
32.
CB
No.
6972,
H.
Fonouni,
10/
5/
90.
33.
DP
Barcodes
D228260
and
D228652,
C.
Olinger,
11/
9/
99.
34.
Adequate
data
are
available
to
reassess
the
tolerance
for
wheat
forage
and
straw.
However,
the
Agency
now
considers
wheat
hay
a
significant
livestock
feed
item
(OPPTS
GLN
860.1000
Table
1.).
A
full
set
of
20
field
trials
as
specified
in
OPPTS
GLN
860.1500
are
required
depicting
carbaryl
residues
in/
on
wheat
hay.
When
all
the
field
trials
are
complete,
PHIs
and
tolerances
for
hay
based
on
the
field
trial
data
should
be
proposed.
Data
on
wheat
hay
will
be
translatable
to
proso
millet
hay.
Table
B
(continued).
74
35.
Data
are
required
depicting
residues
of
carbaryl
in/
on
grass
forage
harvested
immediately
(0
day)
following
the
last
of
two
applications
of
carbaryl
(WP
or
FlC)
at
1.5
lb
ai/
A
to
pasture.
A
total
of
12
field
trials
are
required
in
areas
throughout
the
U.
S.
The
following
data
on
grasses
are
available
for
risk
assessment/
reregistration
purposes:
Residue
data
from
rangeland
field
trials
support
the
current
tolerance
of
100
ppm
in/
on
grass
forage;
as
noted
above,
data
are
still
needed
on
pasture
grass
forage
before
the
tolerance
can
be
reassessed
.
Data
on
pasture
hay
harvested
at
the
14
day
PHI
indicate
that
the
tolerance
on
grass
hay
should
be
lowered
to
15
ppm.
36.
CB
No.
3357,
DP
Barcode:
none,
M.
Nelson,
2/
25/
88.
37.
Based
on
available
data,
a
tolerance
of
70
ppm
should
be
established
for
residues
of
carbaryl
per
se
in/
on
aspirated
grain
fractions.
38.
The
use
of
carbaryl
products
on
cotton
has
been
cnaceled.
39.
The
registrant
intends
to
support
a
tolerance
for
residues
in/
on
imported
pineapple.
Five
residue
field
trials
must
be
submitted,
three
from
Costa
Rica
and
two
from
Mexico.
DP
Barcode
D255348,
11/
2000,
C.
Olinger.
40.
DP
Barcode
D230407,
T.
Morton,
9/
29/
98.
41.
DP
Barcode
D215259,
S.
Hummel,
5/
31/
95.
42.
Residues
resulting
from
the
registered
use
of
carbaryl
on
oyster
beds
in
WA
are
not
likely
to
exceed
the
established
tolerance
(DP
Barcode
D204888,
J
Garbus,
8/
5/
94).
43.
DP
Barcode
D215844,
9/
10/
98,
C.
Olinger.
75
TOLERANCE
REASSESSMENT
SUMMARY
The
HED
Metabolism
Committee
has
concluded
that
the
U.
S.
tolerance
expression
for
plant
commodities
should
be
amended
to
include
only
carbaryl
per
se
(S.
Hummel,
2/
8/
96).
Accordingly,
the
tolerance
definition
for
carbaryl
should
be
amended
to
include
only
parent
carbaryl.
The
tolerance
expression
for
livestock
commodities
should
be
amended
to
include
free
and
conjugated
residues
of
carbaryl,
5,6
dihydro5,6
dihydroxy
carbaryl,
and
5
methoxy
6
hydroxy
carbaryl.
In
addition,
the
tolerances
listed
separately
under
40
CFR
§180.169
(a
through
e)
should
be
pooled
into
three
listings,
one
for
plant
commodity
tolerances
with
national
registrations,
one
for
livestock
commodities,
and
the
third
for
tolerances
with
regional
registrations.
The
food
additive
tolerance
for
residues
in
pineapple
bran
should
be
revoked
as
this
is
no
longer
a
regulated
commodity
(40
CFR
§186.550).
Some
analytical
methods
determine
the
combined
residue
of
carbaryl
and
1
naphthol.
It
should
be
noted
that
1
napthol
is
a
very
minor
part
of
the
residue;
therefore,
the
plant
commodity
tolerances,
which
are
based
on
carbaryl
only,
are
not
greatly
exaggerated.
A
summary
of
carbaryl
tolerance
reassessments
and
recommended
modifications
in
commodity
definitions
are
presented
in
Table
C.
Tolerances
Listed
Under
40
CFR
§180.169(
a),
(b),
(c),
(d),
and
(e):
As
noted
above,
conclusions
pertaining
to
leafy
vegetables
crops
which
retain
post
emergence
granular
uses
are
tentative
pending
submission
of
bridging
residue
data
reflecting
use
of
a
representative
G
formulation
or
revision
of
the
labels
for
the
G
formulations.
In
addition,
supporting
storage
stability
data
are
still
required
for
several
crop
commodities.
Aventis
has
proposed
and/
or
the
available
data
support
the
establishment
of
tolerances
for
residues
in/
on
the
following
crop
groups
and
subgroups:
Brassica
leafy
greens;
bushberry;
caneberry;
cucurbit
vegetables;
dried,
shelled
pea
and
bean
(except
soybean);
edible
podded
legume
vegetables;
foliage
of
legume
vegetables
except
soybeans;
fruiting
vegetables
(excluding
cucurbits);
leaf
petioles;
leaves
of
root
and
tuber
vegetables
(excluding
sugar
beet);
root
and
tuber
vegetables
(excluding
sugar
beet
roots
and
sweet
potatoes);
stone
fruits;
and
tree
nuts
(excluding
walnuts).
As
a
result,
separate
tolerances
on
many
commodities
need
to
be
revoked
concomitant
with
establishing
tolerances
for
the
appropriate
crop
group
and
subgroup.
The
recommended
changes
are
summarized
in
Table
C
under
"Tolerances
Needed
Under
40
CFR
§180.169(
a),
crop
group/
subgroup
tolerances."
Residue
data
are
required
on
pasture
grass
forage
before
the
tolerance
for
residues
in/
on
grass
forage
can
be
reassessed.
Additional
data
are
required
on
pineapple
before
the
tolerance
can
be
reassessed.
Five
trials
must
be
submitted,
three
from
Costa
Rica
and
two
from
Mexico.
The
registrant
is
not
supporting
carbaryl
uses
on
avocados,
barley,
maple
sap,
oats,
and
rye,
and
with
the
exception
of
avocados,
these
uses
have
been
removed
from
the
labels.
IR
4
has
indicated
(Correspondence
from
K.
Dorschner,
IR
4
Project,
9/
15/
94)
that
they
may
be
willing
to
submit
residue
data
for
some
of
these
commodities;
however,
data
have
not
been
submitted.
The
tolerances
for
bean
forage
and
hay
should
be
revoked
because
they
are
no
longer
considered
significant
livestock
feed
items.
76
Data
from
a
ruminant
feeding
study
were
used
as
the
basis
for
reassessing
tolerances
for
residues
in
livestock
commodities.
For
tolerances
on
commodities
of
cattle,
goats,
horses
and
sheep,
the
available
data
support
the
current
tolerances
of
0.1
ppm
for
residues
of
carbaryl
in
meat,
but
indicate
that
the
tolerances
for
fat
are
too
low
and
should
be
increased
to
0.2
ppm;
the
established
tolerance
for
residues
in
milk
should
be
lowered
to
0.1
ppm.
Separate
tolerances
for
residues
in
kidney
and
liver
(1.0
ppm)
and
meat
byproducts
excluding
kidney
and
liver
(0.1
ppm)
should
be
revoked,
and
a
separate
tolerance
for
residues
in
meat
byproducts
should
be
established
at
3.0
ppm.
For
swine
commodities,
the
available
data
indicate
the
established
tolerances
for
carbaryl
residues
in
hog
meat
and
fat
(0.1
ppm)
are
too
high
and
should
be
set
at
0.02
ppm
(the
method
limit
of
quantitation).
Separate
tolerances
for
residues
in
hog
kidney
and
liver
(1.0
ppm
each)
and
meat
byproducts
excluding
kidney
and
liver
(0.1
ppm)
should
be
revoked,
and
a
separate
tolerance
for
residues
in
hog
meat
byproducts
established
at
0.5
ppm.
The
available
residue
data
support
the
establishment
of
separate
tolerances
for
residues
in/
on
various
crop
groups
and
subgroups.
As
a
result,
separate
tolerances
on
many
commodities
need
to
be
revoked
concomitant
with
establishing
new
tolerances
for
residues
in/
on
the
appropriate
crop
groups
and
subgroups.
The
recommended
changes
are
summarized
in
Table
C
under
"Tolerances
Needed
Under
40
CFR
§180.169(
a),
crop
group/
subgroup
tolerances."
New
tolerances
are
also
needed
for
carbaryl
residues
in/
on
the
following
RACs:
aspirated
grain
fractions,
proso
millet
hay,
sorghum
stover,
sugar
beet
roots,
and
wheat
hay.
At
the
present
time,
sufficient
data
are
only
available
to
determine
an
appropriate
tolerance
for
residues
in/
on
aspirated
grain
fractions
(70
ppm),
sugar
beet
roots
(0.5
ppm)
and
sorghum
stover
(30.0
ppm).
Additional
residue
data
are
required
before
appropriate
tolerances
can
be
determined
for
residues
in/
on
the
remaining
commodities;
data
on
wheat
hay
will
be
translatable
to
proso
millet
hay.
Separate
tolerances
are
also
required
for
residues
in
the
following
processed
food/
feed
items:
wet
apple
pomace
(15.0
ppm),
citrus
fruit
oil
(20.0
ppm),
raisins
(12.0
ppm),
and
rice
hulls
(30.0
ppm).
For
livestock
commodities,
the
residue
data
support
establishing
new
tolerances
for
residues
in
meat
byproducts
of
swine
(0.5
ppm)
and
cattle,
goats,
and
sheep
(3.0
ppm);
separate
tolerances
for
residues
in
kidney
and
liver
(1.0
ppm),
and
meat
byproducts
excluding
kidney
and
liver
(0.1
ppm)
should
be
reassigned.
77
(continued;
footnotes
follow)
Table
C.
Tolerance
Reassessment
Summary
for
Carbaryl.
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comments
[Correct
Commodity
Definition]
Tolerance
Listed
Under
40
CFR
§180.169(
a)
Alfalfa
100.0
50.0
Residue
data
indicate
that
the
tolerance
should
be
lowered
to
50.0
ppm.
Alfalfa,
Hay
100.0
75.0
Residue
data
indicate
that
the
tolerance
should
be
lowered
to
75.0
ppm.
Almonds
1.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
0.1
ppm
tolerance
on
the
nuts,
tree
crop
group
(excluding
walnuts).
Almond,
hulls
40.0
50.0
Residue
data
indicate
that
the
tolerance
should
be
increased.
Apricots
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
10.0
ppm
tolerance
on
the
fruit,
stone
crop
group.
Asparagus
10.0
15.0
Residue
data
indicate
that
the
tolerance
should
be
increased.
Banana
10.0
5
Barley,
fodder,
green
100.0
Revoke
The
registrant
does
not
intend
to
support
carbaryl
uses
on
barley.
Barley,
grain
0.0
Barley,
straw
100.0
Beans
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
10.0
ppm
tolerance
for
ediblepodded
legume
vegetables
(
crop
subgroup
6A),
and
a
1.0
ppm
tolerance
for
dried,
shelled
pea
and
bean
(except
soybean)
(crop
subgroup
6C).
Beans,
forage
100.0
Revoke
Tolerance
should
be
revoked.
Bean
forage
and
hay
are
no
longer
considered
significant
livestock
feed
items.
Beans,
hay
100.0
Beets,
garden,
roots
5.0
Reassign
Tolerance
should
be
reassigned
concomitant
with
establishing
a
2.0
ppm
tolerance
on
the
vegetables,
root
and
tuber
crop
group
(excluding
sugar
beets
and
sweet
potatoes).
Beets,
garden,
tops
12.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
75.0
ppm
tolerance
on
the
leaves
of
vegetables,
root
and
tuber
group
(excluding
sugar
beets
tops).
Beets,
sugar,
tops
100.0
25.0
The
available
data
indicate
that
the
tolerance
should
be
lowered.
Table
C
(continued).
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comments
[Correct
Commodity
Definition]
78
(continued;
footnotes
follow)
Blackberries
12.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
12.0
ppm
tolerance
on
the
caneberry
crop
subgroup.
Blueberries
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
3.0
ppm
tolerance
on
the
bushberry
crop
subgroup.
Boysenberries
12.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
12.0
ppm
tolerance
on
the
caneberry
crop
subgroup.
Broccoli
10.0
10.0
Brussels
sprouts
10.0
10.0
Data
on
broccoli
will
translate
to
Brussels
sprouts.
Cabbage
10.0
21.0
The
residue
data
indicate
that
the
tolerance
should
be
increased
to
21.0
ppm.
Cabbage,
chinese
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
10.0
ppm
tolerance
on
the
vegetable,
Brassica
leafy
group.
Carrots
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
2.0
ppm
tolerance
on
the
vegetables,
root
and
tuber
group
(excluding
sugar
beets
and
sweet
potatoes).
Cauliflower
10.0
10.0
Data
on
broccoli
will
translate
to
cauliflower.
Celery
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
3.0
ppm
tolerance
on
the
leaf
petioles
crop
subgroup.
Cherries
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
10.0
ppm
tolerance
on
the
fruit,
stone
group
.
Chestnuts
1.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
0.1
ppm
tolerance
on
the
nut,
tree
group
(excluding
walnuts).
Citrus
fruits
10.0
10.0
Fruit,
citrus,
group
Clover
100.0
50.0
Residue
data
indicate
that
the
tolerance
should
be
lowered
to
50.0
ppm.
Clover,
hay
100.0
70.0
Residue
data
indicate
that
the
tolerance
should
be
lowered
to
70.0
ppm.
Table
C
(continued).
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comments
[Correct
Commodity
Definition]
79
(continued;
footnotes
follow)
Collards
12.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
10.0
ppm
tolerance
on
the
vegetables,
Brassica,
leafy,
group
.
Corn
(inc.
sweet)
(K+
CWHR)
5.0
0.10
Corn,
sweet
(K+
CWHR);
residue
data
indicate
that
a
separate
tolerance
on
sweet
corn
(K+
CWHR)
should
be
established
at
0.1
ppm.
0.02
Corn,
grain,
field
and
pop;
residue
data
indicate
that
a
separate
tolerance
should
be
established
for
corn,
grain
at
0.02
ppm.
Corn,
fodder
100.0
20.0
Corn,
stover
(field
and
pop).
Residue
data
indicate
that
the
tolerance
for
field
and
pop
corn
stover
should
be
lowered
to
20.0
ppm.
215.0
Corn,
sweet,
stover.
Residue
data
indicate
that
the
tolerance
for
sweet
corn
stover
should
be
increased.
Corn,
forage
100.0
30.0
Corn,
field,
forage.
Residue
data
indicate
that
the
tolerance
for
field
corn
forage
should
be
lowered
to
30.0
ppm.
185.0
Corn,
sweet,
forage.
Residue
data
indicate
that
the
tolerance
for
field
corn
forage
should
be
increased.
Cotton,
forage
100.0
Revoke
No
longer
considered
a
significant
feed
item.
Cotton,
seed
5.0
Revoke
The
use
on
cotton
has
been
cancelled.
Cranberries
10.0
3.0
Residue
data
indicate
that
the
tolerance
should
be
lowered
to
3.0
ppm.
Cucumbers
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
3.0
ppm
tolerance
on
the
vegetable,
cucurbit,
group.
Dandelions
12.0
22.0
Residue
data
on
spinach
are
translatable
to
dandelion.
The
residue
data
on
spinach
indicate
that
the
tolerance
must
be
increased.
Dewberry
12.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
12.0
ppm
tolerance
on
the
caneberry
crop
subgroup.
Eggplant
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
5.0
ppm
tolerance
on
the
vegetables,
fruiting,
group
(excluding
cucurbits).
Table
C
(continued).
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comments
[Correct
Commodity
Definition]
80
(continued;
footnotes
follow)
Endive
(escarole)
10.0
10.0
Residue
data
on
lettuce
are
translatable
to
endive.
Filberts
(hazelnuts)
1.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
0.1
ppm
tolerance
on
the
nuts,
tree,
group
(excluding
walnuts).
Flax,
seed
5.0
0.50
Residue
data
support
lowering
the
tolerance.
Flax,
straw
100.0
Revoke
No
longer
considered
a
RAC
of
flax.
Grapes
10.0
10.0
Grasses
100.0
TBD
Grass,
forage.
Residue
data
on
rangeland
grass
forage
harvested
at
a
0
day
PGI
support
the
current
tolerance
of
100
ppm;
data
on
pasture
grass
forage
harvested
at
0
day
PGI
are
needed.
Grasses,
hay
100.0
15.0
Residue
data
on
pasture
hay
indicate
that
the
tolerance
should
be
lowered
to
15.0
ppm.
Horseradish
5.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
2.0
ppm
tolerance
on
the
vegetable,
root
and
tuber,
group
(excluding
sugar
beets
and
sweet
potatoes).
Kale
12.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
10.0
ppm
tolerance
on
the
vegetable,
Brassica,
leafy,
group.
Kohlrabi
10.0
10.0
Residue
data
on
broccoli
are
translatable
to
kohlrabi.
Lentils
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
1.0
ppm
tolerance
on
the
pea
and
bean,
dried
shelled,
except
soybean
group
(6C).
Lettuce
10.0
10.0
Loganberries
12.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
12.0
ppm
tolerance
on
the
caneberry
crop
subgroup.
Maple
sap
0.50
Revoke
The
registrant
is
not
supporting
this
use
Melons
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
3.0
ppm
tolerance
on
the
vegetable,
cucurbit,
group.
Millet,
proso,
grain
3.0
1.0
Residue
data
for
wheat
grain
indicate
that
the
tolerance
should
be
lowered
to
1.0
ppm
Table
C
(continued).
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comments
[Correct
Commodity
Definition]
81
(continued;
footnotes
follow)
Millet,
proso,
straw
100.0
20.0
Adequate
residue
data
on
wheat
straw
are
translatable
to
proso
millet
straw;
the
residue
data
support
lowering
the
tolerance.
Mustard,
greens
12.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
10.0
ppm
tolerance
on
the
vegetable,
Brassica,
leafy,
group.
Nectarines
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
10.0
ppm
tolerance
on
the
fruit,
stone,
group.
Oats,
fodder,
green
100.0
Revoke
The
registrant
does
not
intend
to
support
carbaryl
uses
on
oats
Oats,
grain
0.0
Oats,
straw
100.0
Okra
10.0
4.0
The
available
data
indicate
that
the
tolerance
should
be
lowered.
Olives
10.0
10.0
Oysters
0.25
0.25
Parsley
12.0
22.0
Residue
data
on
spinach
are
translatable
to
parsley;
the
data
indicate
that
the
tolerance
on
parsley
should
be
increased.
Parsnips
5.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
2.0
ppm
tolerance
on
the
vegetable,
root
and
tuber,
group
(excluding
sugar
beets
and
sweet
potatoes).
Peaches
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
10.0
ppm
tolerance
on
the
fruit,
stone,
group.
Peanuts
5.0
0.05
The
available
data
indicate
that
the
tolerance
should
be
lowered.
Peanuts,
hay
100.0
20.0
Residue
data
support
a
lower
tolerance.
Peas,
cowpeas
5.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
1.0
ppm
tolerance
for
dried,
shelled
pea
and
bean
(except
soybean)
group.
Peas,
cowpeas,
Forage
100.0
Reassign
Tolerances
should
be
reassignd
concomitant
with
establishing
a
60.0
ppm
tolerance
for
vegetable,
foliage
of
legume,
group.
Peas,
cowpeas,
Hay
100.0
Peas,
vines
100.0
Table
C
(continued).
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comments
[Correct
Commodity
Definition]
82
(continued;
footnotes
follow)
Peas,
with
pods
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
10.0
ppm
tolerance
for
vegetable,
legume,
edible
podded
subgroup
(crop
subgroup
6A).
Pecans
1.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
0.1
ppm
tolerance
on
the
nuts,
tree,
group
(excluding
walnuts).
Peppers
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
5.0
ppm
tolerance
on
the
vegetable,
fruiting
group
(excluding
cucurbits)
crop
group.
Pistachio
1.0
0.10
Residue
data
indicate
that
the
tolerance
should
be
lowered.
Plums
(fresh
prunes)
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
10.0
ppm
tolerance
on
the
fruit,
stone,
group.
Potatoes
0.20
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
2.0
ppm
tolerance
on
the
vegetable,
root
and
tuber,
group
(excluding
sugar
beets
and
sweet
potatoes).
Prickly
pear
cactus,
fruit
12.0
5.0
Residue
data
indicate
that
the
tolerance
should
be
decreased.
Prickly
pear
cactus,
pads
12.0
12.0
Pumpkins
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
3.0
ppm
tolerance
on
the
vegetable,
cucurbit,
group.
Radishes
5.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
2.0
ppm
tolerance
on
the
vegetable,
root
and
tuber,
group
(excluding
sugar
beets
and
sweet
potatoes).
Raspberry
12.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
12.0
ppm
tolerance
on
the
caneberry
crop
subgroup.
Rice
5.0
15.0
Rice,
grain;
the
residue
data
indicate
that
the
tolerance
should
be
increased.
Rice,
straw
100.0
60.0
Residue
data
support
lowering
the
tolerance
to
60.0
ppm.
Table
C
(continued).
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comments
[Correct
Commodity
Definition]
83
(continued;
footnotes
follow)
Rutabagas
5.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
2.0
ppm
tolerance
on
the
vegetable,
root
and
tuber,
group
(excluding
sugar
beets
and
sweet
potatoes).
Rye,
fodder,
green
100.0
Revoke
The
registrant
does
not
intend
to
support
carbaryl
uses
on
rye
Rye,
grain
0.0
Rye,
straw
100.0
Salsify,
roots
5.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
2.0
ppm
tolerance
on
the
vegetable,
root
and
tuber,
group
(excluding
sugar
beets
and
sweet
potatoes).
Salsify,
tops
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
75.0
ppm
tolerance
on
the
leaves
of
vegetables,
root
and
tuber
vegetables,
group
(excluding
sugar
beets
tops).
Sorghum
grain,
forage
100.0
30.0
Residue
data
indicate
that
the
tolerance
should
be
lowered.
Sorghum
grain,
grain
10.0
10.0
Soybean
5.0
0.50
Residue
data
support
lowering
the
tolerance
to
0.5
ppm.
Soybean,
forage
100.0
15.0
Residue
data
support
lowering
the
tolerance
to
15.0
ppm.
Soybean,
hay
100.0
15.0
Residue
data
support
lowering
the
tolerance
to
15.0
ppm.
Spinach
12.0
22.0
Residue
data
on
spinach
indicate
that
a
higher
tolerance
is
required.
Squash,
summer
10.0
Reassign
Tolerances
should
be
reassignd
concomitant
with
establishing
a
3.0
ppm
tolerance
on
the
vegetable,
cucurbit
group
.
Squash,
winter
10.0
Strawberries
10.0
4.0
Residue
data
indicate
that
the
tolerance
should
be
lowered
to
4.0
ppm.
Sunflower,
seed
1.0
0.50
Residue
data
indicate
that
the
tolerance
should
be
lowered
to
0.5
ppm.
Sweet
potatoes
0.20
0.20
potato,
sweet
Swiss
chard
12.0
Reassign
The
tolerance
should
be
reassignd
concomitant
with
establishing
a
3.0
ppm
tolerance
on
the
leaf
petioles
crop
subgroup.
Table
C
(continued).
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comments
[Correct
Commodity
Definition]
84
(continued;
footnotes
follow)
Tomatoes
10.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
5.0
ppm
tolerance
on
the
vegetables,
fruiting
group(
excluding
cucurbits).
Trefoil,
birdsfoot,
forage
100.0
15.0
Residue
data
on
alfalfa
forage
will
translate
to
trefoil,
forage.
Trefoil,
birdsfoot,
hay
100.0
25.0
Residue
data
on
alfalfa
hay
will
translate
to
trefoil,
hay.
Turnips,
roots
5.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
2.0
ppm
tolerance
on
the
vegetable,
root
and
tuber,
group
(excluding
sugar
beets
and
sweet
potatoes).
Turnips,
tops
12.0
Reassign
Tolerance
should
be
reassignd
concomitant
with
establishing
a
75.0
ppm
tolerance
on
the
leaves
of
vegetables,
root
and
tuber,
group
(excluding
sugar
beets
tops).
Walnuts
1.0
1.0
Wheat,
fodder,
green
100.0
30.0
The
available
data
indicate
that
the
tolerance
should
be
lowered.
Wheat,
forage
Wheat,
grain
3.0
1.0
Residue
data
indicate
that
the
tolerance
should
be
lowered.
Wheat,
straw
100.0
20.0
The
available
data
indicate
that
the
tolerance
should
be
lowered.
Tolerance
Listed
Under
40
CFR
§180.169(
b)
Cattle,
goats,
horses
and
sheep,
fat
0.10
0.50
Residue
data
support
increasing
the
tolerance
Hog,
fat
0.10
0.05
Residue
data
support
lowering
the
tolerance
Cattle,
goats,
horses,
and
sheep,
meat
0.10
1.0
Hog,
meat
0.10
0.10
Table
C
(continued).
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comments
[Correct
Commodity
Definition]
85
(continued;
footnotes
follow)
Cattle,
goats,
horses
and
sheep,
kidney
&
Liver
1.0
Reassign
Tolerances
should
be
reassignd
concomitant
with
establishing
a
3.0
ppm
tolerance
for
meat
byproducts
of
cattle,
goats,
horses,
and
sheep.
Cattle,
goats,
horses,
and
sheep,
mbyp
(exc.
kidney
&
liver)
0.10
Hog,
kidney
&
Liver
1.0
Reassign
Tolerances
should
be
reassignd
concomitant
with
establishing
a
0.5
ppm
tolerance
for
hog
meat
byproducts
Hog,
mbyp
(exc.
kidney
&
liver)
0.10
Poultry,
fat
and
meat
5.0
Revoke
A
Category
3
Tolerance
Listed
Under
40
CFR
§180.169(
c)
Milk
0.30
1.0
Should
be
moved
to
40
CFR
§180.169(
b)
Tolerance
Listed
Under
40
CFR
§180.169(
d)
Pineapple
2.0
TBD
Residue
data
are
required
Pome
fruits
10.0
12.0
The
residue
data
indicate
that
the
tolerance
should
be
increased.
Tolerance
Listed
Under
40
CFR
§180.169(
e)
Avocados
10.0
Revoke
The
registrant
is
not
supporting
this
use.
Dill
(fresh)
0.20
0.20
Interim
Tolerance
Listed
Under
40
CFR
§180.319
Eggs
0.50
Revoke
Category
3.
0Tolerance
Listed
Under
40
CFR
§186.550
Pineapple,
bran,
wet
and
dry
20.0
Revoke
No
longer
considered
a
significant
processed
commodity.
Tolerances
Needed
Under
40
CFR
§180.169(
a)
Separate
plant
commodities
Apple,
wet
pomace
None
15.0
Residue
data
support
establishing
a
15.0
ppm
tolerance
on
wet
apple
pomace.
Aspirated
grain
fractions
None
70
The
available
data
indicate
that
a
tolerance
of
70
ppm
should
be
established
for
residues
in/
on
aspirated
grain
fractions.
Beet,
sugar,
roots
None
0.50
The
available
data
indicate
that
a
tolerance
of
0.5
ppm
should
be
established
for
residues
in/
on
sugar
beet
roots.
Table
C
(continued).
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comments
[Correct
Commodity
Definition]
86
(continued;
footnotes
follow)
Citrus,
fruit,
oil
None
20.0
Residue
data
support
establishing
a
20.0
ppm
tolerance
on
citrus
fruit
oil.
Cotton,
gin
byproducts
None
TBD
Residue
data
are
required.
Grapes,
raisins
None
12.0
Residue
data
support
establishing
a
12.0
ppm
tolerance
on
raisin.
Millet,
proso,
hay
None
TBD
Residue
data
are
required.
Residue
data
required
on
wheat
hay
may
be
translatable
to
proso
millet
hay.
Rice,
hulls
None
30.0
Residue
data
support
establishing
a
30.0
ppm
tolerance
for
residues
in/
on
rice
hulls.
Sorghum,
stover
None
30.0
Residue
data
support
establishing
a
30.0
ppm
on
sorghu
grain,
stover.
Wheat,
hay
None
TBD
Residue
data
are
required.
Livestock
commodities
Cattle,
goats,
horses
and
sheep,
meat
byproducts
None
3.0
Concomitant
with
reassigning
separate
tolerances
for
residues
in
kidney
and
liver
and
meat
byproducts
(excluding
kidney
and
liver),
separate
3.0
ppm
tolerances
are
required
on
meat
byproducts
of
cattle,
goats,
horses,
and
sheep.
Hog,
meat
byproducts
None
0.50
Residue
data
support
establishing
a
0.5
ppm
tolerance
on
meat
byproducts
of
hog;
the
separate
tolerances
for
residues
in
kidney
and
liver
and
meat
byproducts
(excluding
kidney
and
liver)
of
hog
should
be
reassigned.
Croup
group/
subgroups
Brassica
leafy
greens
None
10.0
Concomitant
with
reassigning
separate
tolerances
on
Chinese
cabbage,
collards,
kale,
and
mustard
greens,
a
10.0
ppm
tolerance
on
the
vegetable,
Brassica,
leafy,
group
crop
subgroup
should
be
established.
Bushberry
None
3.0
Residue
data
support
establishing
a
3.0
ppm
tolerance
on
the
bushberry
crop
subgroup;
the
separate
tolerance
on
blueberry
should
be
reassigned.
Table
C
(continued).
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comments
[Correct
Commodity
Definition]
87
(continued;
footnotes
follow)
Caneberry
None
12.0
Concomitant
with
reassigning
separate
tolerances
on
blackberry,
boysenberry,
dewberry,
loganberry,
and
raspberry,
a
12.0
ppm
tolerance
on
the
caneberry
crop
subgroup
should
be
established.
Cucurbit
Vegetables
None
3.0
Residue
data
support
establishing
a
3.0
ppm
tolerance
on
the
vegetable,
cucurbit
groups
crop
group;
separate
tolerances
on
cucumbers,
melons,
pumpkins,
and
summer
and
winter
squash
should
be
reassigned.
Dried,
shelled
pea
and
bean
(except
soybean)
None
1.0
Concomitant
with
reassigning
separate
tolerances
on
beans,
cowpeas,
and
lentils,
a
1.0
ppm
tolerance
should
be
established
on
the
dried,
shelled
pea
and
bean
(except
soybean)
crop
subgroup
(6C).
Edible
podded
legume
vegetables
None
10.0
Concomitant
with
reassigning
separate
tolerances
on
peas
(with
pods),
a
10.0
ppm
tolerance
should
be
established
on
the
edible
podded
legume
vegetables
crop
subgroup
(6A).
Foliage
of
legume
vegetables
except
soybeans
None
60.0
Concomitant
with
reassigning
separate
tolerances
on
cowpea
forage
and
hay,
and
pea
vines,
a
60.0
ppm
tolerance
should
be
established
on
the
foliage
of
legume
vegetables
except
soybeans
crop
subgroup.
Fruiting
vegetables
(excluding
cucurbits)
None
5.0
Residue
data
support
establishing
a
5.0
ppm
tolerance
on
the
vegetables,
fruiting
group(
excluding
cucurbits)
crop
group;
separate
tolerances
on
eggplants,
peppers,
and
tomatoes
should
be
reassigned.
Leaf
petioles
None
3.0
Residue
data
support
establishing
a
3.0
ppm
tolerance
on
the
leaf
petioles
crop
subgroup;
the
separate
tolerances
on
celery
and
swiss
chard
should
be
reassigned.
Leaves
of
root
and
tuber
vegetables
(excluding
sugar
beet)
None
75.0
Concomitant
with
reassigning
separate
tolerances
on
garden
beet,
salsify,
and
turnip
tops,
a
75.0
ppm
tolerance
on
the
leaves
of
root
and
tuber
vegetables
crop
group
(excluding
sugar
beet
tops)
should
be
established.
Table
C
(continued).
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comments
[Correct
Commodity
Definition]
88
Root
and
tuber
vegetables
(excluding
sugar
beet
roots
and
sweet
potatoes)
None
2.0
Concomitant
with
reassigning
separate
tolerances
on
garden
beet
roots,
carrots,
horseradish,
potatoes,
parsnips,
radishes,
rutabagas,
salsify
roots,
and
turnip
roots,
a
2.0
ppm
tolerance
on
the
root
and
tuber
vegetables
crop
group
(excluding
sugar
beet
roots
and
sweet
potatoes)
should
be
established.
Stone
fruits
None
10.0
Concomitant
with
reassigning
separate
tolerances
on
apricots,
cherries,
nectarines,
peaches,
and
plums
(fresh
prunes),
a
10.0
ppm
tolerance
on
the
fruit,
stone,
group
should
be
established.
Tree
nuts
(excluding
walnuts)
None
0.10
Concomitant
with
reassigning
separate
tolerances
on
almonds,
chestnuts,
filberts,
and
pecans,
a
0.1
ppm
tolerance
on
the
nuts,
tree,
group
(excluding
walnuts)
should
be
established.
1
TBD
=
To
be
determined.
Reassessment
of
tolerance(
s)
cannot
be
made
at
this
time
because
additional
data
are
required.
89
CODEX
HARMONIZATION
The
Codex
Alimentarius
Commission
has
established
maximum
residue
limits
(MRLs)
for
carbaryl
residues
in/
on
various
plant
and
livestock
commodities
(see
Guide
to
Codex
Maximum
Limits
For
Pesticide
Residues,
Part
A.
1,
1995).
The
Codex
MRLs
and
U.
S.
tolerances
are
not
compatible
because
the
U.
S.
tolerance
expression
includes
parent
carbaryl
and
its
metabolite
1
naphthol
for
most
raw
crop
commodities
[40
CFR
§180.169(
a)];
tolerances
for
residues
in
livestock
commodities
are
expressed
as
carbaryl
and
its
metabolites
1
naphthol,
5,6
dihydrodihydroxy
carbaryl,
and
5,6
dihydrodihydroxy
naphthol
[40
CFR
§180.169(
b)].
Only
the
established
tolerances
for
residues
in/
on
pineapples,
pome
fruits,
avocados,
and
fresh
dill
are
expressed
in
terms
of
carbaryl
per
se.
However,
the
HED
Metabolism
Committee
(MARC)
determined
that
the
U.
S.
tolerance
expression
for
plant
comodities
be
amended
to
include
only
carbaryl
per
se
(S.
Hummel,
2/
8/
96).
Once
the
U.
S.
tolerance
definition
is
amended,
it
will
be
compatible
with
the
definition
for
Codex
MRLs.
The
MARC
has
recommended
that
the
tolerance
expression
for
livestock
commodities
include
the
free
and
conjugated
forms
of
carbaryl,
5,6
dihydro
5,6
dihydroxy
carbaryl,
and
5
methoxy
6
hydroxy
carbaryl.
The
Codex
MRLs
and
U.
S.
tolerances
cannot
be
made
compatible
for
livestock
commodities
with
respect
to
the
tolerance
definition.
A
comparison
of
the
Codex
MRLs
and
the
corresponding
reassessed
U.
S.
tolerances
is
presented
in
Table
D.
The
following
conclusions
can
be
made
regarding
efforts
to
harmonize
the
U.
S.
tolerances
with
the
Codex
MRLs:
Once
the
U.
S.
tolerance
definition
is
amended
to
include
only
carbaryl
per
se,
U.
S.
tolerances
and
Codex
MRLs
would
be
compatible
for
the
following
crops
and
commodities:
apricot,
beetroot,
carrot,
cherries,
cowpea
(dry),
cucumber,
egg
plant,
hay
or
fodder
(dry)
of
grasses,
leafy
vegetables,
melons
(except
watermelon),
nectarine,
olives,
parsnip,
peppers,
plums
(including
prunes),
pumpkins,
radish,
tomato,
and
winter
squash.
Based
upon
the
use
patterns
registered
in
the
U.
S.
and
the
available
residue
data,
compatibility
of
U.
S.
tolerances
and
Codex
MRLs
is
not
currently
possible
for
the
following
crops/
commodities:
Alfalfa
forage,
apple,
asparagus,
blackberries,
cabbage,
milk,
meat
of
cattle,
goats,
and
sheep,
citrus
fruits,
clover,
common
bean,
cranberry,
dewberries
(including
boysenberry
and
loganberry),
grapes,
maize
forage,
okra,
pea
vines,
peanut
(whole
and
fodder),
pear,
peas
(podded
and
succulent),
potato,
raspberries,
sorghum
forage,
soya
bean
(dry),
soya
bean
forage,
strawberry,
sugar
beet,
sugar
beet
tops,
sweet
corn
(kernels),
and
tree
nuts.
90
(continued;
footnotes
follow)
Table
D.
Codex
MRLs
for
carbaryl
and
applicable
U.
S.
tolerances
for
carbaryl.
Codex
Reassessed
U.
S.
Tolerance
(
ppm)
2
Comments
Commodity,
As
Defined
MRL
(mg/
kg)
1
Step
Alfalfa
forage
(green)
100
CXL
15.0
U.
S
residue
data
support
the
lower
reassessed
tolerance
Apple
5
CXL
12.0
Tolerance
to
be
established
for
pome
fruits
crop
group;
U.
S.
residue
data
indicate
that
the
tolerance
cannot
be
lowered.
Apricot
10
CXL
10.0
Tolerance
to
be
established
for
fruit,
stone,
group
Asparagus
10
CXL
15.0
U.
S
residue
data
support
the
higher
reassessed
tolerance
Banana
5
CXL
5
Barley
5
(Po)
CXL
None
Not
registered
for
use
in
the
U.
S.
Bean
forage
(green)
100
CXL
None
No
longer
regulated
as
a
feed
item
in
the
U.
S.
Beetroot
2
CXL
2.0
Tolerance
to
be
established
on
the
root
and
tuber
vegetables
crop
group
(excluding
sugar
beets
and
sweet
potatoes)
which
includes
garden
beet
roots.
Blackberries
10
CXL
12.0
Tolerance
to
be
established
for
caneberry
crop
subgroup;
U.
S.
residue
data
indicate
that
the
tolerance
cannot
be
lowered.
Blueberries
7
CXL
4.0
Tolerance
to
be
established
for
bushberry
crop
subgroup;
U.
S.
residue
data
support
the
lower
reassessed
tolerance.
Cabbages,
head
5
CXL
21.0
U.
S
residue
data
support
the
higher
reassessed
tolerance
Carrot
2
CXL
2.0
Tolerance
to
be
established
on
the
root
and
tuber
vegetables
crop
group
(excluding
sugar
beets
and
sweet
potatoes).
Cattle
meat
0.2
CXL
1.0
U.
S
tolerance
expression
includes
metabolites
not
included
in
Codex
MRL
expression,
resulting
in
a
higher
numerical
level.
Cherries
10
CXL
10.0
Tolerance
to
be
established
for
fruit,
stone,
group
Table
D
(continued).
Codex
Reassessed
U.
S.
Tolerance
(
ppm)
2
Comments
Commodity,
As
Defined
MRL
(mg/
kg)
1
Step
91
(continued;
footnotes
follow)
Citrus
fruits
7
CXL
10.0
Tolerance
to
be
established
for
citrus
fruits
crop
group;
U.
S.
residue
data
indicate
that
the
tolerance
cannot
be
lowered.
Clover
100
fresh
wt
CXL
50.0
U.
S
residue
data
support
the
lower
reassessed
tolerance
Common
bean
(pods
and
or
immature
seeds)
5
CXL
Tolerance
to
be
established
for
edible10.0
podded
legume
vegetables
(
crop
subgroup
6A);
U.
S.
residue
data
indicate
that
the
tolerance
cannot
be
lowered.
TBD
Data
are
not
available
for
succulent,
shelled
pea
and
beans
Cotton
seed
1
CXL
Revoke
Uses
in
the
U.
S.
are
cancelled.
Cowpea
(dry)
1
CXL
1.0
Tolerance
to
be
established
for
dried,
shelled
pea
and
bean
(except
soybean)
crop
subgroup.
Cranberry
7
CXL
3.0
U.
S
residue
data
support
the
lower
reassessed
tolerance
Cucumber
3
CXL
3.0
Tolerance
to
be
established
for
vegetable,
cucurbit
groups
crop
group
Dewberries
(including
boysenberry
and
loganberry)
10
CXL
12.0
Tolerance
to
be
established
for
caneberry
crop
subgroup;
U.
S.
residue
data
indicate
that
the
tolerance
cannot
be
lowered.
Egg
plant
5
CXL
5.0
Tolerance
to
be
established
for
vegetables,
fruiting
group(
excluding
cucurbits)
crop
group
Eggs
0.5
CXL
None
Dermal
and
poutry
house
uses
cancelled
in
the
U.
S.
Category
3
of
40
CFR
§180.6(
a)
exists
for
U.
S.
Goat
meat
0.2
CXL
1.0
U.
S
tolerance
expression
includes
metabolites
not
included
in
Codex
MRL
expression,
resulting
in
a
higher
numerical
level.
Grapes
5
CXL
10.0
U.
S
residue
data
support
the
higher
reassessed
tolerance
Table
D
(continued).
Codex
Reassessed
U.
S.
Tolerance
(
ppm)
2
Comments
Commodity,
As
Defined
MRL
(mg/
kg)
1
Step
92
(continued;
footnotes
follow)
Hay
or
fodder
(dry)
of
grasses
100
CXL
100.0
Kiwifruit
10
CXL
None
Not
registered
for
use
in
the
U.
S.
Leafy
vegetables
10
CXL
3.0
and
10.0
Tolerances
to
be
established
on
the
Vegetable,
Brassica,
leafy,
group
and
leaf
petioles
crop
subgroups,
10.0
and
3.0
ppm,
respectively,
together
with
separate
tolerances
on
broccoli,
Brussels
sprouts,
cauliflower,
endive,
and
kohlrabi
21.0
U.
S
residue
data
on
spinach
support
the
higher
reassessed
tolerance
Maize
forage
(fresh
wt)
100
CXL
30.0
U.
S
residue
data
on
field
corn
forage
support
the
lower
reassessed
tolerance
185.0
U.
S
residue
data
on
sweet
corn
forage
support
the
higher
reassessed
tolerance
Melons,
except
watermelon
3
CXL
3.0
Tolerance
to
be
established
for
vegetable,
cucurbit
groups
crop
group
Milk
products
0.1(*)
CXL
None
A
U.
S.
tolerance
is
not
established
on
milk
products
Milks
0.1
(*)
CXL
1.0
U.
S
tolerance
expression
includes
metabolites
not
included
in
Codex
MRL
expression,
resulting
in
a
higher
numerical
level.
Nectarine
10
CXL
10.0
Tolerance
established
for
fruit,
stone,
group
Nuts
(whole
in
shell)
except
peanut,
whole
and
tree
nuts
10
CXL
0.1
Tolerance
to
be
established
for
tree
nuts,
except
walnuts
crop
group
Oats
5
(Po)
CXL
None
Not
registered
for
use
in
the
U.
S.
Okra
10
CXL
4.0
U.
S
residue
data
support
the
lower
reassessed
tolerance
Olives
10
CXL
10.0
Olives,
processed
1
CXL
None
U.
S
residue
data
do
not
support
a
separate
tolerance
for
olive
processed
commodities
Table
D
(continued).
Codex
Reassessed
U.
S.
Tolerance
(
ppm)
2
Comments
Commodity,
As
Defined
MRL
(mg/
kg)
1
Step
93
(continued;
footnotes
follow)
Parsnip
2
CXL
2.0
Tolerance
to
be
established
on
the
vegetables,
root
and
tuber,
group
(excluding
sugar
beets
and
sweet
potatoes).
Pea
vines
(green)
(Fresh
wt)
100
CXL
TBD
Residue
data
are
required
(preferably
on
Austrian
winter
pea)
Peanut
fodder
100
CXL
20.0
Tolerance
established
for
peanut
hay;
U.
S.
residue
data
support
the
lower
reassessed
tolerance.
Peanut,
whole
2
CXL
0.05
U.
S.
residue
data
support
the
lower
reassessed
tolerance.
Pear
5
CXL
12.0
Tolerance
to
be
established
for
pome
fruits
crop
group;
U.
S.
residue
data
indicate
that
the
tolerance
cannot
be
lowered.
Peas
(pods
and
succulent
=
immature
seeds)
5
CXL
Tolerance
to
be
established
for
edible10.0
podded
legume
vegetables
(
crop
subgroup
6A);
U.
S.
residue
data
indicate
that
the
tolerance
cannot
be
lowered.
TBD
Data
are
not
available
for
succulent,
shelled
pea
and
beans
Peppers
5
CXL
5.0
Tolerance
to
be
established
for
vegetables,
fruiting
group(
excluding
cucurbits)
crop
group
Plums
(including
prunes)
10
CXL
10.0
Tolerance
to
be
established
for
fruit,
stone,
group
Potato
0.2
CXL
2.0
Tolerance
to
be
established
on
the
root
and
tuber
vegetables
crop
group
(excluding
sugar
beets
and
sweet
potatoes);
U.
S.
residue
data
indicate
that
the
tolerance
cannot
be
lowered.
Poultry
meat
0.5
(V)
CXL
None
Dermal
and
poutry
house
uses
cancelled
in
the
U.
S.
Category
3
of
40
CFR
§180.6(
a)
exists
for
U.
S.
Poultry
skin
5
CXL
None
Pumpkins
3
CXL
3.0
Tolerance
to
be
established
for
vegetable,
cucurbit
groups
crop
group
Table
D
(continued).
Codex
Reassessed
U.
S.
Tolerance
(
ppm)
2
Comments
Commodity,
As
Defined
MRL
(mg/
kg)
1
Step
94
(continued;
footnotes
follow)
Radish
2
CXL
2.0
Tolerance
to
be
established
on
the
root
and
tuber
vegetables
crop
group
(excluding
sugar
beets
and
sweet
potatoes).
Raspberries,
red
and
black
10
CXL
12.0
Tolerance
to
be
established
for
caneberry
crop
subgroup;
U.
S.
residue
data
indicate
that
the
tolerance
cannot
be
lowered.
Rice
5
(PoP)
CXL
15.0
Not
registered
for
postharvest
use
on
rice
and
rye
in
the
U.
S.
Rice,
husked
5
(Po)
CXL
None
Rye
5
(Po)
CXL
None
Sheep
meat
0.2
CXL
1.0
U.
S
tolerance
expression
includes
metabolites
not
included
in
Codex
MRL
expression,
resulting
in
a
higher
numerical
level.
Sorghum
10
(Po)
CXL
None
Not
registered
for
this
use
in
the
U.
S.
Sorghum
forage
(green)
(fresh
wt)
100
CXL
30.0
U.
S
residue
data
support
the
lower
reassessed
tolerance
Soya
bean
(dry)
1
CXL
0.5
U.
S
residue
data
support
the
lower
reassessed
tolerance
Soya
bean
forage
(green)
(fresh
wt)
100
CXL
15.0
U.
S
residue
data
support
the
lower
reassessed
tolerance
Squash,
summer
3
CXL
3.0
Tolerance
to
be
established
for
vegetable,
cucurbit
groups
crop
group
Strawberry
7
CXL
4.0
U.
S
residue
data
support
the
lower
reassessed
tolerance
Sugar
beet
0.2
CXL
0.5
U.
S
residue
data
support
the
higher
reassessed
tolerance
Sugar
beet
leaves
or
tops
100
CXL
25.0
U.
S
residue
data
support
the
lower
reassessed
tolerance
Swede
2
CXL
2.0
Tolerance
to
be
established
on
the
root
and
tuber
vegetables
crop
group
(excluding
sugar
beets
and
sweet
potatoes).
Table
D
(continued).
Codex
Reassessed
U.
S.
Tolerance
(
ppm)
2
Comments
Commodity,
As
Defined
MRL
(mg/
kg)
1
Step
95
Sweet
corn
(kernels)
1
CXL
0.1
U.
S
residue
data
support
the
lower
reassessed
tolerance
for
sweet
corn
(K+
CWHR)
Tomato
5
CXL
5.0
Tolerance
to
be
established
for
vegetables,
fruiting
group(
excluding
cucurbits)
crop
group
Tree
nuts
1
CXL
0.1
Tolerance
to
be
established
for
nuts,
tree,
group
(excluding
walnuts);
U.
S
residue
data
support
the
lower
reassessed
tolerance
1.0
Tolerance
established
for
walnuts
Wheat
5
(Po)
CXL
1.0
Not
registered
for
postharvest
use
on
wheat
in
the
U.
S.
Wheat
bran,
unprocessed
20
(PoP)
CXL
None
Wheat
flour
0.2(
PoP
)
CXL
None
Wheat
wholemeal
2
CXL
None
A
separate
tolerance
on
processed
commodities
of
wheat
is
not
needed
Winter
squash
3
CXL
3.0
Tolerance
to
be
established
for
vegetable,
cucurbit
groups
crop
group
1
An
asterisk
(*)
signifies
that
the
MRL
was
established
at
or
about
the
limit
of
detection.
A
"Po"
or
"PoP"
following
the
MRL
indicate
that
the
MRL
was
established
based
on
postharvest
uses.
2
Recommendations
for
compatibility
are
based
on
conclusions
following
reassessment
of
U.
S.
tolerances
(see
Table
C).
96
AGENCY
MEMORANDA
RELEVANT
TO
REREGISTRATION
Date
DP
Barcode
CB
No.
From
To
MRID
Nos.
Subject
2/
25/
88
None
3357
M.
Nelson
H.
Jamerson
and
Toxicology
Branch
None
PP#
7E3543
Carbaryl
in
or
on
Dill
Amendment
of
1/
18/
88.
3/
28/
88
None
3027
M.
Nelson
D.
Edwards
and
Toxicology
Branch
40376001,
40376002
PP#
7F3490
Carbaryl
in
or
on
Sugar
Beet
Roots
Amendment
of
10/
6/
87.
4/
25/
88
None
3510
M.
Kovacs
H.
Jamerson
and
Toxicology
Branch
40512501
PP#
2E2667
Carbaryl
in
or
on
Potatoes
Amendment
Dated
January
27,
1988.
10/
5/
90
None
6972
H.
Fonouni
W.
Boodee
41594301
Carbaryl
in/
on
Wheat,
Amended
Use
Registration
No.
264
333.
4/
9/
92
D176240
9659
R.
Perfetti
W.
Burnam
and
L.
Rossi
None
Aventis
Ag
Company:
Response
to
the
Carbaryl
Reregistration
Standard:
Residue
Chemistry
Comments.
12/
2/
93
D193129
12374
S.
Hummel
J.
Loranger/
L.
Propst
and
D.
Utterback
None
Carbaryl
(056801)
Anticipated
Residues
for
Carcinogenic
Dietary
Risk
Assessment.
2/
25/
94
D194407
12405
S.
Hummel
J.
Loranger/
L.
Propost
and
D.
Utterback
42883101
42883104
Carbaryl
(056801;
Case
No.
0080)
Field
Trial
Protocols,
Waiver
Requests
Date
DP
Barcode
CB
No.
From
To
MRID
Nos.
Subject
97
8/
5/
94
D204888
13984
J.
Garbus
D.
Edwards
and
R.
Kumar
None
WA
90
0013:
Special
Local
Need
Label
[24(
c)]
for
Carbaryl
(SEVIN
80S)
for
Use
in
Washington
State
on
Oyster
Beds
5/
22/
95
D213142
15275
S.
Hummel
J.
Loranger/
L.
Propst
None
Carbaryl
(056801)
Reregistration
Case
No.
0080
DCI
for
Field
Trials
on
Onions,
Barley,
Oats,
and
Rye;
and
Sweet
Sorghum
Processing
Data
5/
31/
95
D215259
15565
S.
Hummel
Files
None
Carbaryl
(056801)
Reregistration
Case
No.
0080
Analysis
of
Pineapple
Bran
Feed
Additive
Tolerance
with
Respect
to
the
DES
Proviso
11/
28/
9
5
D204197
13831
S.
Hummel
J.
Loranger
43249101
43249103
Carbaryl
(056801)
Reregistration
Case
No.
0080
Metabolism
in
Lettuce,
Radish,
and
Soybeans
GLN
171
4(
a).
11/
28/
9
5
D206777
14249
S.
Hummel
J.
Loranger
43324601
Carbaryl
(056801)
Reregistration
Case
No.
0080
Metabolism
in
Poultry
GLN
171
4(
b).
1/
19/
96
D221978
16669
S.
Hummel
HED
Metabolism
Committee
None
Carbaryl
(056801)
Reregistration
Case
No.
0080
Issues
to
be
presented
to
HED
Metabolism
Committee
on
1/
25/
96
1/
22/
96
D216544
15757
S.
Hummel
J.
Loranger
43672701
43672702
Carbaryl
(056801)
Reregistration
Case
No.
0080
Plant
Analytical
Methods
GLN
171
4(
c),
Independent
Laboratory
Validation
of
Proposed
Enforcement
Method
2/
8/
96
D221979
16670
S.
Hummel
HED
Metabolism
Committee
None
Carbaryl
(056801)
Reregistration
Case
No.
0080
HED
Metabolism
Committee
Decision;
Meeting
on
1/
25/
96.
Date
DP
Barcode
CB
No.
From
To
MRID
Nos.
Subject
98
3/
15/
96
D211172
16516
S.
Hummel
J.
Loranger
None
Carbaryl
(056801)
Reregistration
Case
No.
0080
Metabolism
in
Lettuce,
Radish,
and
Soybeans
GLN
171
4(
a)
Corrected
Study
Pages
for
MRIDs
43249101
and
43249103
(Update
to
CB
13831,
DP
Barcode
D204197).
8/
21/
96
D225659,
D226582
17209,
17243
F.
Suhre
J.
Loranger
43984701,
43996101
Carbaryl
(056801)
Reregistration
Case
No.
0080
Magnitude
of
the
Residue
in
Succulent
Bean
and
Tomato;
GLN
171
4(
k)
9/
13/
96
D218865,
D219999,
D220949,
D221158,
D223008,
D219971,
D220601,
D220948,
D221313,
D225204,
D225576
16140,
16364,
16555,
16559,
16887,
16329,
16460,
16556,
16584,
17127,
17147
F.
Suhre
P.
Deschamp
43786801,
43793201,
43793202,
43802101
43802103,
43818901,
43845205,
43850901,
43850902,
43915201,
43975601,
43982801
Carbaryl
(056801)
Reregistration
Case
No.
0080
Magnitude
of
the
Residue
Studies
(GLN
171
4(
k))
on
Several
Crops;
Processing
Studies
(GLN
171
4(
l))
on
Field
Corn,
Cottonseed,
and
Sunflower;
Storage
Stability
Studies
(GLN
171
4(
e))
for
Representative
Crops.
10/
7/
96
D217179,
D217172,
D217177,
D217631,
D217704,
D217705
15829,
15830,
15832,
15897,
15946,
15952
F.
Suhre
P.
Deschamp
43677401,
43686701,
43686702,
43694101
43694105,
43697601
43697604,
43698201
43698203,
43702001
43702003,
43703101
43703103,
43716601,
43721001
Carbaryl
(056801)
Reregistration
Case
No.
0080
Magnitude
of
the
Residue
(GLN
171
4(
k))
and
Processing
(GLN
171
4(
l))
studies
on
numerous
crops.
9/
11/
97
D234692
None
C.
Olinger
J.
Loranger
None
Carbaryl:
Over
Tolerance
Residues
on
Spinach;
Chemical
No.
56801.
Date
DP
Barcode
CB
No.
From
To
MRID
Nos.
Subject
99
1/
22/
98
D240441
None
C.
Olinger
K.
Boyle
None
Carbaryl:
Request
for
Waiver
of
Field
Trials
Using
Granular
Formulation;
Chemical
No.
56801
4/
9/
98
D240998,
D237653
None
C.
Olinger
V.
Dobozy
44321301
and
44412501
Reregistration
of
Carbaryl:
Olive
Field
Trial
and
Wheat
Storage
Stability;
Chemical
No.
56801.
5/
12/
98
D227765,
D227009
17424
17444
M.
Perry
J.
Loranger
44019701,
44046101
Carbaryl.
Aventis
Ag
Company.
Reregistration
Case
No.
0080.
Peanut
Processing
Study
and
Amended
Report
to
Broccoli
Field
Trial
Study.
5/
22/
98
D230900,
D231134
17626
and
17655
M.
Perry
J.
Loranger
44123101,
44145201
Carbaryl.
PC
Code
056801.
Reregistration
Case
No.
0080.
IR
4
Submission
of
Okra
and
Prickly
Pear
Magnitude
of
the
Residue
Studies
(GLN
860.1500)
5/
26/
98
D230246,
D230406,
D231533
17610,
17606,
and
17689
M.
Perry
J.
Loranger
44058101,
44072901,
and
44155401
Carbaryl.
PC
Code
056801.
Reregistration
Case
No.
0080.
Magnitude
of
the
Residue
Data
in/
on
Sweet
Corn
and
Pome
Fruits
and
ILV
Data
on
Enforcement
Method
for
Oily
Crops.
9/
10/
98
D215844
None
C.
Olinger
V.
Dobozy
43651701
Reregistration
of
Carbaryl:
Confined
Rotational
Crop
Study;
Chemical
No.
56801.
9/
29/
98
D230407
None
T.
Morton
K.
Boyle
44114301
Carbaryl
Reregistration
Evaluation
of
tobacco
pyrolysis
study
to
satisfy
GLN
860.1500.
9/
17/
98
D206443
14130
T.
Morton
K.
Boyle
None
Carbaryl
(056801);
Reregistration
Case
No.
0080)
Review
of
Revised
Labels
for
EPA
Reg.
No.
264
315
and
264
321.
Date
DP
Barcode
CB
No.
From
To
MRID
Nos.
Subject
100
9/
17/
98
D216242,
D219527,
D219596,
and
D220287
15690,
16235,
16266,
and
16384
T.
Morton
K.
Boyle
43654201,
43786802
43786806,
43794901
43794903,
43813601
43813604
Carbaryl:
PC
Code
56801,
Case
No.
0080.
Residue
Analytical
Methods,
and
Magnitude
of
the
Residue
in/
on
Asparagus;
Beans
(dry);
Cabbage;
Cucurbits;
Mustard
Greens;
Root
and
Tuber
Vegetables
including
Beets,
Carrots,
and
Turnips;
Sorghum;
Sunflowers;
and
Processed
Commodities
of
Rice;
Sorghum;
Soybeans;
and
Wheat.
5/
6/
99
D255855
None
C.
Olinger
G.
Kramer
None
Metabolism
of
Carbaryl
in
Dairy
Cattle;
Briefing
Memorandum
for
HED
Metabolism
Assessment
Review
Committee;
Chemical
No.
56801
6/
17/
99
D255855
None
C.
Olinger
G.
Kramer
None
Metabolism
of
Carbaryl
in
Dairy
Cattle;
HED
Metabolism
Assessment
Review
Committee
Decision
Memorandum;
Chemical
No.
56801
11/
9/
99
D228656
and
D235113
None
C.
Olinger
V.
Dobozy
44068401,
44250301
Reregistration
of
Carbaryl:
Storage
Stability
Studies;
Chemical
No.
56801
11/
9/
99
D228260
and
D228652
None
C.
Olinger
V.
Dobozy
44321301,
44412501
Reregistration
of
Carbaryl:
Field
Corn
and
Rangeland
Grass
Field
Trial
Studies;
Chemical
No.
56801
11/
9/
99
D236422
and
D236485
None
C.
Olinger
V.
Dobozy
44321301,
44412501
Reregistration
of
Carbaryl:
Stone
Fruit
and
Orange
Field
Trial
Studies;
Chemical
No.
56801
12/
15/
9
9
D236574,
D236421,
D240469
None
C.
Olinger
V.
Dobozy
44250901,
44286901
44286903,
44381901
Reregistration
of
Carbaryl:
Livestock
Analytical
Method,
Storage
Stability,
and
Magnitude
of
Residue
Studies;
Chemical
No.
56801
Date
DP
Barcode
CB
No.
From
To
MRID
Nos.
Subject
101
10/
2000
D266186
None
F.
Fort
V.
Dobozy
45115402,
45115403,
45115404,
45115405,
45115406,
45115407,
45115408,
45115409,
45189102
Reregistration
of
Carbaryl:
Magnitude
of
the
Residue
in/
on
Various
Cops
Resulting
from
Ground
Applications
of
Liquid
and
Granular
Formulations,
Chemical
No.
56801
102
MASTER
RECORD
IDENTIFICATION
NUMBERS
[Note:
references
for
MRIDs
05001852
05019959,
representing
published
material,
were
unavailable
for
citation]
00015669
Knaak,
J.
B.;
Tallant,
M.
J.;
Bartley,
W.
J.;
et
al.
(1965)
The
metabolism
of
Carbaryl
in
the
rat,
guinea
pig,
and
man.
Journal
of
Agricultural
and
Agricultural
and
Food
Chemistry
13(
6):
537
543.
(Also
in
unpublished
submission
received
Sep
26,
1974
under
5G1553;
submitted
by
Ciba
Geigy
Corp.,
Greensboro,
N.
C.;
CDL:
094221
C)
00049135
Kuhr,
R.
J.;
Casida,
J.
E.
(1966?)
Persistent
Glycosides
of
Metabolites
of
Methylcarbamate
Insecticide
Chemicals
Formed
by
Hydroxylation
in
Bean
Plants:
Report
No.
19547.
(Unpublished
study
received
Jul
15,
1976
under
3125
EX
135;
prepared
by
Univ.
of
California
Berkeley,
Div.
of
Entomology,
submitted
by
Mobay
Chemical
Corp.,
Kansas
City,
Mo.;
CDL:
226512
G)
00053897
Union
Carbide
Corporation
(1975)
Introduction:
[Carbaryl].
(Reports
by
various
sources;
unpublished
study
including
published
data,
received
Oct
14,
1976
under
7F1878;
CDL:
095306
B)
00058927
Union
Carbide
Corporation
(1977)
Determination
of
Carbaryl
Residues
in
Sunflowers.
Method
dated
May
1977.
(Unpublished
study
received
Jan
7,
1980
under
5E1564;
submitted
by
Interregional
Research
Project
No.
4,
New
Brunswick,
N.
J.;
CDL:
099745
B)
00058928
Interregional
Research
Project
Number
4
(1978)
Carbaryl:
Residue
Tolerance
Petition
Sunflowers.
(Reports
by
various
sources;
unpublished
study
received
on
unknown
date
under
5E1564;
CDL:
099745
C)
00061103
Johnson,
D.
P.;
Critchfield,
F.
E.;
Arthur,
B.
W.
(1963)
Determination
of
Sevin
insecticide
and
its
metabolites
in
poultry
tissues
and
eggs.
Journal
of
Agricultural
and
Food
Chemistry
11(
1):
77
80.
(Also
In
unpublished
submission
received
1963
under
unknown
ad
min.
no.;
submitted
by
Union
Carbide
Corp.,
Arlington,
Va.;
CDL:
129334
D)
00061106
Claborn,
H.
V.;
Roberts,
R.
H.;
Mann,
H.
D.;
et
al.
(1963)
Residues
in
body
tissues
of
livestock
sprayed
with
Sevin
or
given
Sevin
in
the
diet.
Journal
of
Agricultural
and
Food
Chemistry
11(
1):
74
76.
(Also
In
unpublished
submission
received
1963
under
unknown
admin.
no.;
submitted
by
Union
Carbide
Corp.,
Arlington,
Va.;
CDL:
129334
H)
00074366
Interregional
Research
Project
Number
4
(1979)
Carbaryl:
Residue
Tolerance
Petition
Flax.
(Compilation;
unpublished
study
received
Apr
7,
1981
under
1E2498;
CDL:
099997
A)
00074367
McBride,
D.
K.
(1979)
Carbaryl
(Sevin)
Residue
Trial
Flax
(PR#
1084).
(Unpublished
study
received
Apr
7,
1981
under
1E2498,
prepared
by
North
Dakota
State
Univ.
of
Agriculture
and
Applied
Science,
submitted
by
Interregional
Research
Project
No.
4,
New
Brunswick,
N.
J.;
CDL:
099997
C)
00074368
Interregional
Research
Project
Number
4
(1979)
Carbaryl:
Residue
Tolerance
Petition
Millet:
Summary.
(Compilation;
unpublished
study
received
Apr
7,
1981
under
1E2497;
CDL:
099998
A)
103
00080419
Annand,
A.
M.;
Robinson,
D.
H.
(1965)
Residues
of
Sevin
in
Tissues
of
Cattle
Dipped
at
Various
Frequencies
in
Sevin
Cattle
Dip:
Report
No.
230/
102/
2.
(Unpublished
study
received
Jun
1,
1966
under
7E0518;
submitted
by
Union
Carbide
Corp.,
South
Charleston,
W.
Va.;
CDL:
090613
F)
00080420
Claborn,
H.
V.;
Roberts,
R.
H.;
Mann,
H.
D.;
et
al.
(1963)
Residues
in
body
tissues
of
livestock
sprayed
with
Sevin
or
given
Sevin
in
the
diet.
Journal
of
Agricultural
and
Food
Chemistry
II(
1):
74
76.
(Also
in
unpublished
submission
received
Jun
1,
1966
under
7E0518;
submitted
by
Union
Carbide
Corp.,
South
Charleston,
W.
Va.;
CDL:
090613
G)
00080679
Union
Carbide
Corporation
(1971)
Metabolism
of
Carbaryl
in
Animals:
Summary.
Summary
of
studies
091048
R,
091048
S,
091048
U,
091048
V
and
091048
AB.
(Unpublished
study
received
Dec
22,
1971
under
2F1220;
CDL:
091048
O)
00080680
Andrawes,
N.
R.;
Chancey,
E.
L.;
Crabtree,
R.
J.;
et
al.
(1971)
Fate
of
Naphthyl
1
14
C
Carbaryl
in
Laying
Chickens.
(Unpublished
study
received
Dec
22,
1971
under
2F1220;
submitted
by
Union
Carbide
Corp.,
Arlington,
Va.;
CDL:
091048
P)
00080681
Baron,
R.
L.;
Locke,
R.
K.
(1970)
Utilization
of
cell
culture
techniques
in
carbaryl
metabolism
studies.
Bulletin
of
Environmental
Contamination
&
Toxicology
5(
4):
287
291.
(Also
in
unpublished
submission
received
Dec
22,
1971
under
2F1220;
submitted
by
Union
Carbide
Corp.,
Arlington,
Va.;
CDL:
091048
Q)
00080682
Bartley,
W.
J.
(1970)
Sevin
Metabolism
Studies:
The
Identification
of
a
New
Metabolite
of
Sevin
in
Milk:
Project
No.
111A12,
File
No.
14750.
(Unpublished
study
received
Dec
22,
1971
under
2F1220;
submitted
by
Union
Carbide
Corp.,
Arlington,
Va.;
CDL:
091048
R)
00080683
Bartley,
W.
J.
(1971)
Sevin
Metabolism
Studies:
The
Identification
of
3,4
Dihydro
3,4
dihydroxy
1
naphthyl
Methylcarbamate
in
Milk
a
New
Sevin
Metabolite:
Project
No.
111A12,
File
No.
15133.
(Unpublished
study
received
Dec
22,
1971
under
2F1220;
submitted
by
Union
Carbide
Corp.,
Arlington,
Va.;
CDL:
091048
S)
00080686
Dorough,
H.
W.
(1971)
Carbaryl
Residues
in
Milk
and
Meat
of
Dairy
Animals.
(Unpublished
study
received
Dec
22,
1971
under
2F1220;
prepared
by
Univ.
of
Kentucky,
Dept.
of
Entomology,
submitted
by
Union
Carbide
Corp.,
Arlington,
Va.;
CDL:
091048
V)
00080689
Pekas,
J.
C.
(1971)
Intestinal
metabolism
and
transport
of
Naphthyl
N
methylcarbamate
in
vitro
(rat).
American
Journal
of
Physiology
220(
6):
2008
2012.
(Also
in
unpublished
submission
received
Dec
22,
1971
under
2F1220;
submitted
by
Union
Carbide
Corp.,
Arlington,
Va.;
CDL:
091048
Y)
00080690
Pekas,
J.
C.;
Paulson,
G.
D.
(1970)
Intestinal
hydrolysis
and
conjugation
of
a
pesticidal
carbamate
in
vitro.
Science
170:
77
78.
(Also
in
unpublished
submission
received
Dec
22,
1971
under
2F1220;
submitted
by
Union
Carbide
Corp.,
Arlington,
Va.;
CDL:
091048
Z)
00082420
Union
Carbide
&
Carbon
Corporation
(1958)
Summary:
[Results
of
Residue
Determinations
on
Apples
with
Sevin].
(Compilation;
unpublished
study
received
Oct
15,
1958
under
PP0193;
CDL:
092469
J)
104
00082422
Union
Carbide
&
Carbon
Corporation
(1958)
Summary:
[Residues
of
Sevin
on
Peaches].
(Unpublished
study
received
Oct
15,
1958
under
PP0193;
CDL:
092469
L)
00082423
Carbide
and
Carbon
Chemicals
Company
(1957)
Alpha
Naphthyl
N
Methyl
Carbamate
(Experimental
Insecticide
Sevin):
Determination
of
Residues
in
Apples.
Method
30
U1A15
4
dated
Feb
20,
1957.
(Unpublished
study
received
Oct
15,
1958
under
PP0193;
CDL:
092469
M)
00082424
Union
Carbide
&
Carbon
Corporation
(1958)
Summary:
[Results
of
Residue
Determinations
on
Beans].
(Unpublished
study,
including
letter
dated
Sep
15,
1958
from
C.
E.
Herald
to
J.
W.
Keays,
received
Oct
15,
1958
under
PP0193;
CDL:
092469
O)
00083311
Union
Carbide
&
Chem.
(1957)
Summary:
[Evidence
of
Residues
of
Sevin
on
Apples].
(Compilation;
unpublished
study
received
Nov
14,
1957
under
PP0155;
CDL:
090181
D)
00083312
Whitehurst,
W.
E.;
Johnson,
J.
B.
(1957)
alpha
Naphthyl
N
Methyl
carbamate:
Determination
of
Residues
in
Apples:
File
No.
300
U1A15;
1543
I1.
Interim
rept.
Method
dated
Feb
26,
1957.
(Unpublished
study
received
Nov
14,
1957
under
PP0155;
submitted
by
Union
Carbide
&
Chem.,
New
York,
N.
Y.;
CDL:
090181
E)
00083527
Union
Carbide
Corporation
(19??)
Sevin
Residues
in
Asparagus:
Summary
and
Discussion.
(Unpublished
study
received
Oct
2,
1961
under
PP0333;
CDL:
092615
C)
00089348
Union
Carbide
&
Carbon
Corporation
(1959)
Summary:
[Sevin
Residue
Plums].
(Compilation;
unpublished
study
received
Aug
21,
1959
under
PP0222;
CDL:
090250
A)
00089376
Union
Carbide
&
Carbon
Corporation
(1959)
The
Results
of
Tests
on
the
Amount
of
Residue
Remaining
on
Cucumbers
and
Summer
Squash
Including
a
Description
of
the
Analytical
Method
Used:
[Sevin].
(Compilation;
unpublished
study
received
Dec
7,
1959
under
PP0236;
CDL:
090264
A)
00089378
Union
Carbide
&
Carbon
Corporation
(1960)
Results
of
Tests
To
Determine
Sevin
Residues
in
Corn
(Kernels
Only
and
Kernel
plus
Cob
with
Husk
Removed)
and
in
Corn
Fodder
and
Forage.
(Compilation;
unpublished
study
received
Jan
5,
1960
under
PP0243;
CDL:
090270
A)
00089380
Whitehurst,
W.
E.;
Bishop,
E.
T,;
Critchfield,
F.
E.
(1960)
Sevin
Insecticide:
A
Study
of
the
Metabolic
Fate
in
Dairy
Cows:
Project
No.
328B.
Final
rept.
(Unpublished
study
received
Jan
5,
1960
under
PP0243;
submitted
by
Union
Carbide
&
Carbon
Corp.,
New
York,
N.
Y.;
CDL:
090270
C)
00089418
Union
Carbide
&
Carbon
Corporation
(1958)
Summary:
[Sevin
and
1
Naphthol
Residue
Analyses].
Includes
method
no.
30
U1A15
7
dated
Jul
9,
1958.
(Compilation;
unpublished
study
received
Dec
19,
1958
under
PP0203;
CDL:
090231
A)
00089420
Union
Carbide
&
Carbon
Corporation
(1958)
Summary:
[Sevin
and
1
Naphthol
Residue
Analyses].
Includes
method
no.
30
U1A15
7
dated
Jul
9,
1958.
(Compilation;
unpublished
study
received
Dec
19,
1958
under
PP0203;
CDL:
090231
C)
00089455
Union
Carbide
&
Carbon
Corporation
(1957)
Summary:
[Residues
of
Sevin
on
Pears].
(Compilation;
unpublished
study
received
Jan
31,
1958
under
PP0165;
CDL:
090191
A)
105
00089458
Union
Carbide
&
Carbon
Corporation
(1957)
Summary:
[Analyses
for
Sevin
Residues
on
Grapes].
Includes
method
30
U1A15
4
dated
Feb
20,
1957.
(Compilation;
unpublished
study
received
Feb
24,
1958
under
PP0169;
CDL:
090196
A)
00089600
Union
Carbide
&
Carbon
Corporation
(1959)
The
Results
of
Tests
on
the
Amount
of
Residue
Remaining
on
Tomatoes,
Eggplants
and
Peppers
Including
a
Description
of
the
Analytical
Method
Used:
[Sevin].
Includes
method
30
U1A15
7
dated
Jul
9,
1958.
(Compilation;
unpublished
study
received
Oct
30,
1959
under
PP0228;
CDL:
090257
A)
00089679
Union
Carbide
&
Carbon
Corporation
(1957)
Summary:
[Residues
of
Sevin
on
Beans].
(Compilation;
unpublished
study
received
Feb
6,
1958
under
PP0167;
CDL:
090193
A)
00089680
Carbide
and
Carbon
Chemicals
Company
(1957)
Alpha
Naphthyl
N
Methyl
Carbamate
(Experimental
Insecticide
Sevin):
Determination
of
Residues
in
Apples.
Method
30
U1A15
4
dated
Feb
20,
1957.
(Unpublished
study
received
Feb
6,
1958
under
PP0167;
CDL:
090193
B)
00089681
Swango,
W.
H.;
Herald,
C.
E.;
Massie,
J.
L.;
et
al.
(1957)
Insecticide
Sevin:
Determination
on
Green
Beans:
File
No.
307
U
1A15.
Final
rept.
(Unpublished
study
received
Feb
6,
1958
under
PP0167;
submitted
by
Union
Carbide
&
Carbon
Corp.,
New
York,
N.
Y.;
CDL:
090193
C)
00089836
U.
S.
Agricultural
Research
Service
(1960)
Residues
in
Animal
Tissues
following
Dermal
Application
and
Feeding
with
Sevin:
Special
Report
K
64.
(Unpublished
study;
CDL:
090343
B)
00089837
Union
Carbide
Corporation
(1961)
Results
of
Tests
To
Determine
Residues
of
Sevin
in
(1)
the
Green
Forage
and/
or
Cured
Hay
or
Crop
Refuse
of
Alfalfa,
Bean,
Clovers,
Cotton,
Cowpea,
Grasses,
Peanut,
Rice,
Sorghum,
Soybean,
Sugarbeet,
and
(2)
in
Sorghum
Grain,
Cowpeas,
Peanuts,
Rice
and
Soybean.
(Compilation;
unpublished
study
received
Mar
10,
1961
under
PP0302;
CDL:
090343
C)
00089868
Union
Carbide
Chemicals
Company
(1962)
Results
of
Tests
To
Determine
Sevin
Residues
in
Spinach
Group,
Lettuce
Group,
Blackberry
Group
and
Root
Crops.
(Compilation;
unpublished
study
received
on
unknown
date
under
PP0368;
CDL:
090397
B)
00090113
Union
Carbide
Chemicals
Company
(1961)
Sevin
Residues
in
Garden
Peas
and
Pea
Vines.
(Unpublished
study
received
Nov
12,
1962
under
PP0387;
CDL:
090419
A)
00090156
Union
Carbide
Corporation
(1960)
Sevin
for
Use
on
Filberts:
Insect
Control
and
Residue
Data:
April
1960.
(Compilation;
unpublished
study
received
Oct
7,
1960
under
PP0277;
CDL:
090299
B)
00090160
Union
Carbide
&
Carbon
Corporation
(1960)
Sevin
Residues
in
Apricots
and
Nectarines.
(Compilation;
unpublished
study
received
Nov
25,
1960
under
PP0281;
CDL:
090303
A)
00090161
Union
Carbide
&
Carbon
Corporation
(1960)
Sevin
Residues
in
Cranberries
and
Blueberries.
(Compilation;
unpublished
study
received
Nov
25,
1960
under
PP0281;
CDL:
090303
B)
00090162
Union
Carbide
&
Carbon
Corporation
(1960)
Sevin
Residues
on
Lettuce.
(Compilation;
unpublished
study
received
Nov
25,
1960
under
PP0281;
CDL:
090303
C)
106
00090204
Union
Carbide
&
Carbon
Corporation
(1961)
Summary
Sevin
Residues
on
Citrus.
(Compilation;
unpublished
study
received
May
5,
1961
under
PP0313;
CDL:
090331
A)
00090229
Union
Carbide
Corporation
(1961)
The
Results
of
Tests
on
the
Amount
of
Residue
Remaining
on
Okra
Including
a
Description
of
the
Analytical
Method
Used:
[Sevin].
(Unpublished
study
received
Feb
10,
1961
under
PP0296;
CDL:
090316
A)
00090281
Union
Carbide
Corporation
(1961)
Sevin
Residues
in
Olives.
(Compilation;
unpublished
study
received
Nov
20,
1961
under
PP0337;
CDL:
090367
A)
00090320
Union
Carbide
Corporation
(1961)
Summary
Sevin
Residue
in
Citrus.
(Compilation;
unpublished
study
received
Aug
4,
1961
under
PP0327;
CDL:
090354
A)
00090325
Union
Carbide
Corporation
(1961)
Results
of
Tests
To
Determine
Sevin
Residues
in
Cabbage;
Broccoli,
Brussels
Sprouts,
Cauliflower
and
Kohlrabi,
Melons,
Pumpkins
and
Winter
Squash,
and
Carrots.
(Compilation;
unpublished
study
received
Jun
14,
1961under
PP0318;
CDL:
090346
A)
00091952
Oonnithan,
E.
S.;
Casida,
J.
E.
(1968)
Oxidation
of
methyl
and
dimethylcarbamate
insecticide
chemicals
by
microsomal
enzymes
and
anticholinesterase
activity
of
the
metabolites.
Journal
of
Agricultural
and
Food
Chemistry
16(
1):
28044.
(Also
in
unpublished
submission
received
Jun
9,
1971
under
3125
EX
118;
submitted
by
Mobay
Chemical
Corp.,
Kansas
City,
Mo.;
CDL:
126996
E)
00095927
Dorough,
H.
W.
(1970)
Metabolism
of
insecticidal
methylcarbamates
in
animals.
Journal
of
Agricultural
and
Food
Chemistry
18(
6):
1015
1022.
(Also
In
unpublished
submission
received
Jan
18,
1971
under
9F0843;
submitted
by
Shell
Chemical
Co.,
Washington,
D.
C.;
CDL:
093138
AC)
00098504
Interregional
Research
Project
Number
4
(1980)
Summary
of
Residue
Data
for
Carbaryl
in
or
on
Potatoes
from
Postharvest
Treatment.
(Compilation;
unpublished
study
received
Apr
7,
1982
under
2E2667;
CDL:
070770
A)
00103288
Interregional
Research
Project
No.
4
(1981)
The
Results
of
Tests
on
the
Amount
of
Carbaryl
Residues
Remaining
in
or
on
Prickley
Pear
Cactus
Including
a
Description
of
the
Analytical
Method
Used.
(Compilation;
unpublished
study
received
Jun
17,
1982
under
2E2712;
CDL:
070930
A)
00107017
Union
Carbide
(1965)
The
Results
of
Analyses
on
the
Amount
of
Residue
Remaining
on
or
in
Irish
Potatoes
and
Sweet
Potatoes:
[Sevin].
(Compilation;
unpublished
study
received
Sep
19,
1966
under
7F0537;
CDL:
090655
A)
00108985
Prudich,
J.;
Herald,
C.;
Zweig,
G.
(1961)
Summary:
[Residue
Determinations
for
Sevin
on
Walnuts
and
Almonds].
(Unpublished
study
received
Aug
17,
1961
under
PP0329;
prepared
in
cooperation
with
Univ.
of
California
Berkeley,
submitted
by
Union
Carbide
Corp.,
New
York,
NY;
CDL:
090356
A)
00115284
Union
Carbide
Corp.
(1977)
The
Results
of
Tests
on
the
Amount
of
Residue
Remaining
Including
a
Description
of
the
Analytical
Method
Used:
[Sevin].
(Compilation;
unpublished
study
received
Dec
23,
1977
under
1016
EX
39;
CDL:
096707
A)
107
00116083
Union
Carbide
Corp.
(1971)
The
Results
of
Tests
on
the
Amount
of
Residue
Remaining
Including
a
Description
of
the
Methods
Used:
[Sevin
Carbaryl].
(Compilation;
unpublished
study
received
Jul
17,
1972
under
2F1220;
CDL:
091049
A)
00118342
Union
Carbide
Corp.
(1969)
[Study:
Carbaryl
Residue
in
Milk,
Oysters,
and
Selected
Crops].
(Compilation;
unpublished
study
received
May
15,
1970
under
0F0902;
CDL:
091556
E)
00118346
Knaak,
J.;
Tallant,
M.;
Kozbelt,
S.;
et
al.
(1968)
The
metabolism
of
carbaryl
in
man,
monkey,
pig,
and
sheep.
J.
Agr.
Food
Chem.
16(
3):
465
470.
16(
3):
465
470.
(Also
in
unpublished
submission
received
May
15,
1970
under
0F0902;
submitted
by
Union
Carbide
Corp.,
New
York,
NY;
CDL:
091556
J)
00118347
Knaak,
J.;
Sullivan,
L.
(1967)
Metabolism
of
carbaryl
in
the
dog.
J.
Agr.
Food
Chem.
15(
6):
1125.
(Also
in
unpublished
submission
received
May
15,
1970
under
0F0902;
submitted
by
Union
Carbide
Corp.,
New
York,
NY;
CDL:
091556
K)
00118365
Union
Carbide
Corp.
(1969)
Metabolism
of
Carbaryl
in
Animals:
Summary.
(Unpublished
study
received
May
15,
1970
under
0F0902;
CDL:
091556
AD)
00118366
Baron,
R.
(1968)
Radioactive
lactose
in
skim
milk
following
administration
of
carbonyl
14Ccarbaryl
to
a
lactating
cow.
Journal
of
the
Assoc.
Off.
Anal.
Chem.
51(
5):
1046
1049.
(Also
In
unpublished
submission
received
May
15,
1970
under
0F0902;
submitted
by
Union
Carbide
Corp.,
New
York,
NY;
CDL:
091556
AE)
00118367
Baron,
R.;
Palmer,
N.;
Ross,
R.;
et
al.
(1968)
Distribution
of
radioactivity
in
milk
resulting
from
oral
administration
of
14C
labelled
carbaryl.
Journal
of
the
Assoc.
Off.
Anal.
Chem.
51
(1):
32
34.
(Also
In
unpublished
submission
received
May
15,1970
under
0F0902;
submitted
by
Union
Carbide
Corp.,
New
York,
NY;
CDL:
091556
AF)
00118368
Baron,
R.;
Sphon,
J.;
Chen,
J.;
et
al.
(1969)
Confirmatory
isolation
and
identification
of
a
metabolite
of
carbaryl
in
urine
and
milk.
Journal
of
Agricultural
and
Food
Chemistry
17(
4):
883
887.
(Also
In
unpublished
submission
received
May
15,
1970
under0F0902;
submitted
by
Union
Carbide
Corp.,
New
York,
NY;
CDL:
091556
AG)
00118370
Dorough,
H.
(1967)
Carbaryl
C14
metabolism
in
a
lactating
cow.
Agricultural
and
Food
Chemistry
15(
2):
261
266.
(Also
In
unpublished
submission
received
May
15,
1970
under
0F0902;
submitted
by
Union
Carbide
Corp.,
New
York,
NY;
CDL:
091556
AI)
00118371
Dorough,
H.
(1969)
Continuous
Feeding
of
Sevin
naphthyl
C14
to
Lactating
Cows.
Progress
rept.,
Jun
17,
1969.
(Unpublished
study
received
May
15,
1970
under
0F0902;
prepared
by
Univ.
of
Kentucky,
Dept.
of
Entomology,
submitted
by
Union
Carbide
Corp.,
New
York,
NY;
CDL:
091556
AJ)
00118372
Dorough,
H.;
Casida,
J.
(1964)
Nature
of
certain
carbamate
metabolites
of
the
insecticide
Sevin.
Agricultural
and
Food
Chemistry
12(
4):
294
304.
(Also
In
unpublished
submission
received
May
15,
1970
under
0F0902;
submitted
by
Union
Carbide
Corp.,
New
York,
NY;
CDL:
091556
AK)
108
00118373
Dorough,
H.;
Leeling,
N.;
Casida,
J.
(1963)
Nonhydrolic
pathway
in
metabolism
of
Nmethylcarbamate
insecticides.
Science
140(
Apr
12):
170
171.
(Also
In
unpublished
submission
received
May
15,
1970
under
0F0902;
submitted
by
Union
Carbide
Corp.,
New
York,
NY;
CDL:
091556
AL)
00118374
Dorough,
H.;
Wiggins,
O.
(1969)
Nature
of
the
water
soluble
metabolites
of
carbaryl
in
bean
plants
and
their
fate
in
rats.
Journal
of
Economic
Entomology
62(
1):
49
53.
(Also
In
unpublished
submission
received
May
15,
1970
under
0F0902;
submitted
by
Union
Carbide
Corp.,
New
York,
NY;
CDL:
091556
AM)
00118375
Paulson,
G.;
Feil,
V.
(1969)
The
Fate
of
a
Single
Oral
Dose
of
Carbaryl
...
in
the
Chicken.
(Unpublished
study
received
May
15,
1970
under
0F0902;
prepared
by
U.
S.
Agricultural
Research
Service,
Metabolism
and
Radiation
Research
Laboratory,
Animal
Husbandry
Research
Div.,
submitted
by
Union
Carbide
Corp.,
New
York,
NY;
CDL:
091556
AO)
00118376
Paulson,
G.;
Zaylskie,
R.;
Zehr,
M.;
et
al.
(1969)
Metabolites
of
Carbaryl
...
in
Chicken
Urine.
(Unpublished
study
received
May
15,
1970
under
0F0902;
prepared
by
U.
S.
Agricultural
Research
Service,
Metabolism
and
Radiation
Research
Laboratory,
Animal
Husbandry
Research
Div.
and
Entomology
Research
Div.,
submitted
by
Union
Carbide
Corp.,
New
York,
NY;
CDL:
091556
AP)
00118377
Sullivan,
L.
(1969)
5,6
Dihydro
5,6
dihydroxycarbaryl
Glucuronide
as
a
Significant
Metabolite
of
Carbaryl
in
the
Rat:
Special
Report
32
100.
(Unpublished
study
received
May
15,
1970
under
0F0902;
prepared
by
Mellon
Institute,
submitted
by
Union
Carbide
Corp.,
New
York,
NY;
CDL:
091556
AQ)
00118378
Whitehurst,
W.;
Bishop,
E.;
Critchfield,
F.;
et
al.
(1963)
The
metabolism
of
Sevin
in
dairy
cows.
Agricultural
and
Food
Chemistry
11(
2):
167
169.
(Also
In
unpublished
submission
received
May
15,
1970
under
0F0902;
submitted
by
Union
Carbide
Corp.,
New
York,
NY;
CDL:
091556
AR)
00123219
Interregional
Research
Project
No.
4
(1972)
The
Results
of
Tests
on
the
Amount
of
Carbaryl
Residues
Remaining
on
or
in
Pecans,
Including
a
Description
of
the
Analytical
Method
Used.
(Compilation;
unpublished
study
received
Oct
18,
1972
under
3E1324;
CDL:
093553
A)
00124334
Union
Carbide
Corp.
(1977)
The
Results
of
Tests
on
the
Amount
of
Carbaryl
Residues
Remaining
in
or
on
Lentils
and
Lentil
Forage
and
Hay,
Including
a
Description
of
the
Analytical
Method
Used.
(Compilation;
unpublished
study
received
Sep
13,
1978
under1016
68;
CDL:
097397
A)
00124335
Interregional
Research
Project
No.
4
(1978)
The
Results
of
Tests
on
the
Amount
of
Carbaryl
Residues
Remaining
in
or
on
Pistachios.
(Compilation;
unpublished
study
received
Nov
21,
1978
under
9E2153;
CDL:
097652
A)
00124337
Interregional
Research
Project
No.
4
(1965)
Results
of
Tests
Concerning
the
Amount
of
Carbaryl
Residue
Remaining
in
or
on
Celery,
Including
a
Description
of
the
Analytical
Method
Used.
(Compilation;
unpublished
study
received
Mar
11,
1977
under7E1935;
CDL:
097769
A)
00124343
Herald,
C.;
Wene,
G.
(1959)
Residue
Analyses
for
Sevin
on
Cotton
Seed
Crop
and
Variety:
Reference
T
797
142.
(Unpublished
study
received
on
unknown
date
under
PP0212;
submitted
by
Union
Carbide
Agricultural
Products
Co.,
Inc.,
Research
Triangle
Park,
NC;
CDL:
098737
A)
109
00124345
Union
Carbide
Agricultural
Products
Co.,
Inc.
(1959)
[Residues:
Sevin].
(Compilation;
unpublished
study
received
1959
under
PP0222;
CD:
098753
A)
00124353
Herrett,
R.;
Bagley,
W.;
Kramer,
J.
(1966)
Insecticide
Sevin:
Uptake
and
Distribution
in
Corn:
855
31047
8019.
(Unpublished
study
received
Oct
5,
1966
under
unknown
admin.
no.;
submitted
by
Union
Carbide
Corp.,
Research
Triangle
Park,
NC;
CDL:
121177
A)
00124361
Gutenmann,
W.;
Lisk,
D.
(1964)
Gas
Chromatographic
Residue
Determination
of
Sevin
as
Brominated
1
Naphthyl
Acetate.
(Unpublished
study
received
1964
under
unknown
admin.
no.;
prepared
by
Cornell
Univ.,
Dept.
of
Entomology,
submitted
by
?;
CDL:
121435
A)
00124367
Union
Carbide
Corp.
(1963)
Summary
of
Sevin
and
1
Naphthol
Residues
in
Poultry,
Meat
and
Eggs:
Hens
Treated
by
Dust
bath
box
Method.
(Unpublished
study
received
Mar
13,
1963
under
unknown
admin.
no.;
CDL:
121450
A)
00124968
Abdel
Wahab,
A.;
Kuhr,
R.;
Casida,
J.
(1966)
Fate
of
C14
carbonyl
labeled
aryl
methylcarbamate
insecticide
chemicals
in
and
on
bean
plants.
J.
Agr.
Food
Chem.
14(
3):
290
297.
(Submitter
18274;
also
In
unpublished
submission
received
Jul
15,
1976under
3125
EX
135;
submitted
by
Mobay
Chemical
Corp.,
Kansas
City,
MO;
CDL:
227756
E)
00125084
Union
Carbide
Agricultural
Products
Co.,
Inc.
(19??)
[Sevin
Residues
in
Leaves
and
Other
Subjects].
(Compilation;
unpublished
study
received
Feb
24,
1958
under
PP0169;
CDL:
092447
A)
00125090
Union
Carbide
Agricultural
Products
Co.,
Inc.
(1959)
[Study
of
the
Residue
of
Sevin
in
Milk,
Fruit
and
Vegetables].
(Compilation;
unpublished
study
received
Feb
17,
1959;
Jan
22,
1959
under
PP0193;
CDL:
092470
A)
00125099
Union
Carbide
Agricultural
Products
Co.,
Inc.
(1959)
The
Results
of
Tests
on
the
Amount
of
Residue
Remaining,
Including
a
Description
of
the
Analytical
Method
Used:
[Sevin].
(Compilation;
unpublished
study
received
Mar
3,
1959;
Jul
9,
1959;
Jun
8,1959
under
PP0212;
CDL:
092490
A)
00125107
Union
Carbide
Agricultural
Products
Co.,
Inc.
(1960)
[Residues:
Sevin].
(Compilation;
unpublished
study
received
1960
under
PP0243;
CDL:
092520
A)
00125121
Union
Carbide
Agricultural
Products
Co.,
Inc.
(1960)
The
Results
of
Tests
on
the
Amount
of
Residue
Remaining
on
Alfalfa,
Grass
Forage,
Sorghum
Forage
and
Sorghum
Grain,
Including
a
Description
of
the
Analytical
Methods
Used:
[Sevin].
(Compilation;
unpublished
study
received
1960
under
PP0263;
CDL:
092540
A)
00125123
Union
Carbide
Agricultural
Products
Co.,
Inc.
(1960)
[Residues:
Sevin].
(Compilation;
unpublished
study
received
Nov
28,
1960
under
PP0263;
CDL:
092541
A)
00125138
Union
Carbide
Agricultural
Products
Co.,
Inc.
(1961)
[Residues:
Sevin].
(Compilation;
unpublished
study
received
Mar
14,
1960
under
PP0302;
CDL:
092582
A)
00125170
Union
Carbide
Agricultural
Products
Co.,
Inc.
(1974)
The
Results
of
Tests
on
the
Amount
of
Residues
Remaining,
Including
a
Description
of
the
Methods
Used:
[Carbaryl].
(Compilation;
unpublished
study
received
1974
under
2F1220;
CDL:
094079
L)
110
00125555
Union
Carbide
Agricultural
Products
Co.,
Inc.
(1963)
[Sevin:
Residues
in
Wheat
and
Other
Crops].
(Compilation;
unpublished
study
received
May
3,
1963
under
PP0405;
CDL:
092693
C)
00125571
Union
Carbide
Agricultural
Products
Co.,
Inc.
(1963)
The
Results
of
Analyses
on
the
Amount
of
[Carbaryl]
Residue
Remaining
on
or
in
Eggs.
(Compilation;
unpublished
study
received
Sep
24,
1966
under
7F0538;
CDL:
092826
B)
00134421
Union
Carbide
Corp.
(1958)
Sevin
Insecticide
Residues
in
Potatoes.
(Compilation;
unpublished
study
received
Dec
22,
1958
under
unknown
admin.
no.;
CDL:
121475
A)
00135678
Union
Carbide
Agricultural
Products
Co.,
Inc.
(1961)
[Residue:
Sevin
in
Poultry
Meat].
(Compilation;
unpublished
study
received
1961
under
PP0311;
CDL:
092591
B)
00135680
Union
Carbide
Agricultural
Products
Co.,
Inc.
(1961)
[Residue:
Sevin
in
Poultry
Products].
(Compilation;
unpublished
study
received
Mar
23,
1961
under
PP0311;
CDL:
092592
B)
00136415
Romine,
R.
(1979)
Residue
Data
Transmittal:
[Carbaryl
in
or
on
Wheat].
(Unpublished
study
received
Aug
9,
1979
under
264
316;
submitted
by
Union
Carbide
Agricultural
Products
Co.,
Inc.,
Research
Triangle
Park,
NC;
CDL:
098950
A)
00139664
Dorough,
H.
(1971)
Carbaryl
Residues
in
Milk
and
Meat
of
Dairy
Animals.
(Unpublished
study
received
Dec
1,
1971
under
2F1220;
prepared
by
Univ.
of
Kentucky,
Dept.
of
Entomology,
submitted
by
Union
Carbide
Agricultural
Products
Co.,
Inc.,
Research
Triangle
Park,
NC;
CDL:
111825
W)
00140447
Union
Carbide
Agricultural
Products
Co.,
Inc.
(1962)
[Residue:
Sevin
in
Almonds
and
Filberts].
(Compilation;
unpublished
study
received
1962
under
PP0329;
CDL:
092611
A)
00140449
Union
Carbide
Agricultural
Products
Co.,
Inc.
(1961)
[Residue:
Sevin
on
Asparagus].
(Compilation;
unpublished
study
received
1961
under
PP0333;
CDL:
092616
B)
00145884
Interregional
Research
Project
No.
4
(1984)
The
Results
of
Tests
on
the
Amount
of
Carbaryl
Residues
Remaining
in
or
on
Loquats
Including
a
Description
of
the
Analytical
Method
Used.
Unpublished
study.
30
p.
00147760
Interregional
Research
Project
No.
4.
(1984)
The
Results
of
Tests
on
the
Amount
of
Carbaryl
Residues
Remaining
in
or
on
Avocado
Including
a
Description
of
the
Analytical
Method
Used.
Unpublished
compilation.
27
p.
00154626
Union
Carbide
Agricultural
Products
Co.,
Inc.
(1984)
Results
of
Tests
on
the
Amount
of
Residue
Remaining
Including
a
Description
of
the
Analytical
Method
Used:
Carbaryl
on
or
in
Pineapples
.
Unpublished
compilation.
26
p.
00156736
Union
Carbide
Agricultural
Products
Co.
(1985)
Sevin
(Carbaryl)
Residues
in
Pineapple
Products.
Unpublished
compilation.
29
p.
00159324
Davis,
C.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Potato
Processing
Study:
Project
No.
801R11:
File
No.
34477.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
20
p.
111
00159325
Davis,
C.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Alfalfa
Processing
Study:
Project
No.
801R11:
File
No.
34398.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
11
p.
00159326
Davis,
C.;
Thomas,
S.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Tomato
Processing
Study:
Project
No.
801R11:
File
No.
34397.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
13
p.
00159327
Davis,
C.;
Thomas,
S.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Apple
Processing
Study:
Project
No.
801R11:
File
No.
34443.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
13
p.
00159328
Davis,
C.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Prune
Processing
Study:
Project
No.
801R11:
File
No.
34438.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
8
p.
00159329
Davis,
C.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Sweet
Sorghum
Processing
Study:
Project
No.
801R11:
File
No.
34413.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.
Inc.
13
p.
00163006
Davis,
C.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Magnitude
of
Carbaryl
Residues
on
Rangeland
and
Pasture
Grasses:
Project
No.
801R11.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
in
cooperation
with
Hazleton
Laboratories,
Inc.
78
p.
00163007
Thomas,
S.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Magnitude
of
Carbaryl
Residues
in
Sugar
Beet
Roots:
Project
No.
801R11.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
in
cooperation
with
Hazleton
Laboratories
America,
Inc.
28
p.
00163008
Davis,
C.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Citrus
Processing
Study:
Residue
Data
in
Grapefruits,
Oranges,
and
Lemons:
Project
No.
801R11.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
in
cooperation
with
Univ.
of
Florida,
Citrus
Research
and
Education
Center.
46
p.
00163009
Davis,
C.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Field
Corn
Processing
Study:
Residue
Data:
Project
No.
801R11.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
in
cooperation
with
Texas
A&
M
University,
Food
Protein
Center
and
US
Dept.
of
Agriculture,
Northern
Regional
Research
Center.
22
p.
00163010
Davis,
C.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Grape
Processing
Study:
Residue
Data:
Project
No.
801R11.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
in
cooperation
with
Agricultural
Chemicals
Development
Services,
Inc.
13
p.
00163011
Davis,
C.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Magnitude
of
Carbaryl
Residues
in
Raisins
and
Raisin
Waste:
Project
No.
801R11.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
15
p.
00163012
Davis,
C.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Peanut
Processing
Study:
Residue
Data:
Project
No.
801R11.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
in
cooperation
with
Texas
A&
M
Univ.,
Food
Protein
Center.
18
p.
112
00163013
Davis,
C.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Rice
Processing
prepared
bu
Union
Carbide
Agricultural
Products
Co.,
Inc.
in
cooperation
with
Univ.
of
Arkansas,
Dept.
of
Entomology.
15
p.
00163014
Davis,
C.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Magnitude
of
Carbaryl
Residues
in
Snap
Bean
Cannery
Waste:
Project
No.
801R11.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
19
p.
00163015
Davis,
C.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Grain
Sorghum
Processing
Study:
Project
No.
801R11:
File
No.
34847.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
12
p.
00163016
Davis,
C.;
Thomas,
S.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Soybean
Processing
Study:
Project
No.
801R11.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
in
cooperation
with
Texas
A&
M
Univ.,
Food
Protein
Center.
17
p.
00163017
Davis,
C.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Sugar
Beet
Processing
Study:
Project
No.
801R11.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
16
p.
00163018
Davis,
C.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Magnitude
of
Carbaryl
Residues
in
Sweet
Corn
Cannery
Waste:
Project
No.
801R11.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
19
p.
05008444
Baron,
R.
L.
(1978)
Terminal
residues
of
carbamate
insecticides.
Pure
and
Applied
Chemistry
50(
5):
505
509.
40255702
Davis,
C.
(1986)
Sevin
Brand
Carbaryl
Insecticide:
Magnitude
of
Carbaryl
Residues
in
Sweet
Corn
Cannery
Waste:
Project
No.:
801R11:
File
No.:
34830.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
21
p.
40376001
Davis,
C.;
Thomas,
S.
(1985)
Sevin
Brand
Carbaryl
Insecticide:
Method
of
Analysis
for
Carbaryl
in
Alfalfa
(Modified
to
Include
Sugar
Beets):
Laboratory
Project
ID:
801R11;
File
No:
33769.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
17
p.
40376002
Davis,
C.
(1987)
Data
in
Support
of
Sugar
Beet
Root:
Residue
Data
Submitted
as
Part
of
Pesticide
Petition
#
7F3490.
Unpublished
compilation
prepared
by
Aventis
Ag
Co.
42
p.
40408601
Davis,
C.;
Thomas,
S.
(1987)
Carbaryl
Insecticide:
Magnitude
of
the
Residue
Crop
Field
Trials:
Barley:
Project
No.
801R11
and
File
No.
40092.
Unpublished
study
prepared
by
Union
Carbide
Agricultural
Products
Co.,
Inc.
in
cooperation
with
Hazleton
Laboratories
America,
Inc.
136
p.
40512501
Sorensen,
K.;
Sheets,
T.;
Markle,
G.
(1987)
Carbaryl
Magnitude
of
Residues
on
Potato
(Post
Harvest):
Project
No.
402.
Unpublished
study
prepared
by
North
Carolina
State
Univ.
31
p.
40881302
Butler,
L.;
McDonough,
L.
(1970)
Specific
glc
method
for
determining
residues
of
carbaryl
by
electron
capture
detection
after
derivative
formation.
Journal
of
the
AOAC
53(
3):
494
499.
40881307
Pablo,
F.;
Bello,
F.
(19??)
Carbaryl
and
monocrotophos
residues
in
cottonseeds,
oil
and
cake.
Phillipine
Entomologist
(?):
301
309.
113
40881308
Nir,
I.;
Weisenberg,
E.;
Hadani,
A.;
et
al.
(1966)
Studies
of
the
toxicity,
excretion
and
residues
of
sevin
in
poultry
p.
719
728.
40881309
McCay,
C.;
Arthur,
B.
(1962)
Sevin
residues
in
poultry
products.
Journal
of
Economic
Entomology
55(
6):
936
938.
40881312
Johnson,
D.
(1963)
Determination
of
Sevin
insecticides
residues
in
fruits
and
vegetables.
Journal
of
the
AOAC
46(
2):
233
237.
40881313
Johnson,
D.
(1964)
Determination
of
sevin
insecticide
residues
in
fruits
and
vegetables.
Journal
of
the
AOAC
47(
2):
282
287.
40881314
Miskus,
R.;
Gordon,
H.;
George,
D.
(1959)
Colorimetric
determination
of
1
naphthyl
nmethylcarbamte
in
agricultural
crops.
Agricultural
and
Food
Chemistry
7(?):
612
614.
41594301
Lee,
R.
(1990)
Carbaryl
Insecticide:
Wheat:
Residues
Examination
of
Residue
Levels
in/
on
Forage,
Straw
and
Grain
at
Selected
PreHarvest
Intervals:
Lab
Project
Number:
S86
054
02:
40533.
Unpublished
study
prepared
by
Aventis
Ag
Co.
79
p.
43249101
Harsy,
S.
(1994)
Metabolic
Fate
and
Distribution
of
(carbon
14)
Carbaryl
in
Lettuce:
Final
Report:
Lab
Project
Number:
HWI
6224
188:
EC
92
231.
Unpublished
study
prepared
by
Hazleton
Wisconsin,
Inc.
125
p.
43249102
Harsy,
S.
(1994)
Metabolic
Fate
and
Distribution
of
(carbon
14)
Carbaryl
in
Radishes:
Final
Report:
Lab
Project
Number:
HWI
6224
186:
EC
92
232.
Unpublished
study
prepared
by
Hazleton
Wisconsin,
Inc.
164
p.
43249103
Harsy,
S.
(1994)
Metabolic
Fate
and
Distribution
of
(carbon
14)
Carbaryl
in
Soybeans:
Final
Report:
Lab
Project
Number:
HWI
6224
190:
EC
92
233.
Unpublished
study
prepared
by
Hazleton
Wisconsin,
Inc.
178
p.
43324601
Struble,
C.
(1994)
Nature
of
the
Residue
of
(carbon
14)
Carbaryl
in
Laying
Hens:
Final
Report:
Lab
Project
Number:
HWI
6224
183:
EC
92
223.
Unpublished
study
prepared
by
Hazleton
Wisconsin,
Inc.
157
p.
43651701
Harsy,
S.
(1995)
(Carbon
14)
Carbaryl
Accumulation
in
Confined
Rotational
Crops
(Screenhouse
Study):
Lab
Project
Number:
HWI
6224
192:
EC
94
284.
Unpublished
study
prepared
by
Hazleton
Wisconsin,
Inc.
180
p.
43654201
Chancey,
E.
(1995)
Sevin
XLR
Plus:
Carbaryl
Residues
in/
on
Asparagus
Raw
Agricultural
Commodities:
Final
Study
Report:
Lab
Project
Number:
44695:
US94S20R:
94
0143.
Unpublished
study
prepared
by
Aventis
Ag
Co.
239
p.
43672701
Thiem,
D.
(1995)
Method
Validation
for
Aventis
Ag
Company
Method
No.
CACR
0194
Revised
March
27,
1995:
Carbaryl
General
Method
for
the
Determination
of
Residue
in
Crop
Samples
by
High
Performance
Liquid
Chromatography:
Final
Report:
Lab
Project
Number:
44754:
1247.
Unpublished
study
prepared
by
Colorado
Analytical
Research
&
Development
Corp.
353
p.
114
43672702
Humble,
G.;
Herzig,
R.
(1995)
Independent
Laboratory
Confirmation
of
the
Tolerance
Enforcement
Method
by
EPA
Notice
88
5
for
Carbaryl:
General
Method
for
the
Determination
of
Residues
in
Crop
Samples
by
High
Performance
Liquid
Chromatography:
Final
Report:
Lab
Project
Number:
RES9544:
44778:
8765.
Unpublished
study
prepared
by
Agvise
Labs,
Inc.
120
p.
43677401
Tew,
E.;
Koktavy,
K.
(1995)
Sevin
XLR
PLUS:
Magnitude
of
Carbaryl
Residues
in
Leafy
Vegetables
(Celery,
Head
Lettuce,
Leaf
Lettuce,
and
Spinach):
Lab
Project
Number:
US94S04R:
44749.
Unpublished
study
prepared
by
Research
Designed
for
Agriculture;
Ag
Consulting
Inc.;
Agsearch
Co.
608
p.
43686701
Ely,
C.
(1995)
Carbaryl:
Magnitude
of
Carbaryl
Residues
in
Bell
Peppers
Following
Treatment
with
SEVIN
XLR
PLUS:
Final
Report:
Lab
Project
Number:
94
0059:
44758:
US94S14R.
Unpublished
study
prepared
by
EN
CAS
Analytical
Labs.
262
p.
43686702
Lee,
R.
(1995)
SEVIN
XLR
PLUS:
Carbaryl
Tomato
Processing
(Magnitude
of
Residues):
Final
Report:
Lab
Project
Number:
44759:
US94S01R:
94
0001.
Unpublished
study
prepared
by
Aventis
Ag
Co.
228
p.
43694101
Mede,
K.
(1995)
CARBARYL:
Magnitude
of
Residues
in/
on
Blueberries
Resulting
from
Ground
Application
of
SEVIN
XLR
PLUS
(1994):
Final
Report:
Lab
Project
Number:
94
0177:
94
0178:
94
0179.
Unpublished
study
prepared
by
Enviro
Bio
Tech
and
Aventis.
216
p.
43694102
Robinson,
P.
(1995)
Carbaryl:
Magnitude
of
Carbaryl
Residue
in/
on
Soybeans:
Final
Report:
Lab
Project
Number:
US94S41R:
44740:
94
0248.
Unpublished
study
prepared
by
Agri
Business
Group,
Inc.
459
p.
43694103
Robinson,
P.
(1995)
Carbaryl:
Magnitude
of
Carbaryl
Residue
in/
on
Dried
Peas:
Final
Report:
Lab
Project
Number:
US94S39R:
44737:
94
0232.
Unpublished
study
prepared
by
Agri
Business
Group,
Inc.
291
p.
43694104
Robinson,
P.
(1995)
SEVIN
XLR
PLUS:
Carbaryl
Citrus
Processing
(Orange):
Final
Report:
Lab
Project
Number:
94
0095:
US94S10R:
44734.
Unpublished
study
prepared
by
Agri
Business
Group,
Inc.
248
p.
43694105
Singer,
G.
(1995)
Carbaryl:
Magnitude
of
Residues
in/
on
Clover
Forage
and
Clover
Hay
Resulting
from
a
Ground
Application
of
SEVIN
XLR
PLUS:
Final
Report:
Lab
Project
Number:
94
0321:
94
0322:
94
0323.
Unpublished
study
prepared
by
American
Agricultural
Services,
Inc.
488
p.
43697601
Robinson,
P.
(1995)
Sevin
XLR
PLUS:
Carbaryl:
Grape
Processing
(Raisins):
Final
Report:
Lab
Project
Number:
US94S13R:
44733:
94
0098.
Unpublished
study
prepared
by
Agri
Business
Group,
Inc.
468
p.
43697602
Robinson,
P.
(1995)
Sevin
XLR
PLUS:
Carbaryl:
Grape
Processing
(Juice):
Final
Report:
Lab
Project
Number:
US94S12R:
44732:
94
0097.
Unpublished
study
prepared
by
Agri
Business
Group,
Inc.
312
p.
115
43697603
Robinson,
P.
(1995)
Carbaryl:
Magnitude
of
Carbaryl
Residue
in
Processed
Potato
Fractions
Following
Field
Treatment
with
Sevin
XLR
Plus:
Final
Report:
Lab
Project
Number:
US94S21R:
44742:
94
149.
Unpublished
study
prepared
by
Agri
Business
Group,
Inc.
319
p.
43697604
Mede,
K.
(1995)
Carbaryl:
Magnitude
of
Residue
in/
on
Cranberries
Resulting
from
Ground
Applications
of
Sevin
XLR
Plus
(1994):
Final
Report:
Lab
Project
Number:
US94S28R:
44780:
94
0181.
Unpublished
study
prepared
by
Aventis
Ag
Co.
and
Enviro
Bio
Tech,
Ltd.
216
p.
43698201
Lee,
R.
(1995)
Carbaryl:
Magnitude
of
Residues
in/
on
Caneberries
Resulting
from
Ground
Applications
of
Sevin
XLR
Plus
(1994):
Final
Report:
Lab
Project
Number:
US94S18R:
44760:
94
0173.
Unpublished
study
prepared
by
Aventis
Ag
Co.
220
p.
43698202
Mede,
K.
(1995)
Carbaryl:
Magnitude
of
Residues
in/
on
Strawberries
Resulting
from
Ground
Applications
of
Sevin
XLR
Plus
(1994):
Final
Report:
Lab
Project
Number:
US94S30R:
44765:
94
0195.
Unpublished
study
prepared
by
Aventis
Ag
Co.
and
Enviro
Bio
Test,
Ltd.
216
p.
43698203
Robinson,
P.
(1995)
Determination
of
the
Magnitude
of
Residues
in
Olive
Oil
Processed
from
Olives
Treated
with
Sevin
XLR
Plus
Brand
of
Carbaryl
Insecticide:
Final
Report:
Lab
Project
Number:
US94S02R:
44731:
94
002.
Unpublished
study
prepared
by
Agri
Business
Group,
Inc.
263
p.
43702001
Macy,
L.;
Lee,
R.
(1995)
Carbaryl:
Determination
of
the
Magnitude
of
Residues
on
Olives
Treated
with
Foliar
Applications
of
SEVIN
XLR
Plus
Brand
of
Carbaryl
Insecticide:
Final
Report:
Lab
Project
Number:
US94S09R:
44791:
94
0091.
Unpublished
study
prepared
by
Colorado
Analytical
Research
&
Development
Corp.
and
Aventis
Ag
Co.
288
p.
43702002
Kowite,
W.
(1995)
Carbaryl:
Magnitude
of
Residues
in
Sweet
Potato
RAC
Resulting
from
Applications
of
SEVIN
XLR
Plus
Insecticide
(1994):
Final
Report:
Lab
Project
Number:
US94S16R:
44794:
94
0117.
Unpublished
study
prepared
by
Colorado
Analytical
Research
&
Development
Corp.
and
Aventis
Ag
Co.
367
p.
43702003
Cappy,
J.
(1995)
Carbaryl:
Magnitude
of
Carbaryl
Residues
in/
on
Apples
and
Processed
Fractions
of
Apples:
Final
Report:
Lab
Project
Number:
US94S11R:
44773:
94
0096.
Unpublished
study
prepared
by
Enviro
Bio
Tech,
Ltd.
and
Aventis
Ag
Co.
263
p.
43703101
Kowite,
W.
(1995)
Carbaryl:
Magnitude
of
Residues
in
Peanuts
RAC
Resulting
From
Application
of
Sevin
XLR
PLUS
Insecticide
(1994):
Final
Report:
Lab
Project
Number:
US94S22R:
44795:
94
0150.
Unpublished
study
prepared
by
Enviro
Bio
Tech,
Ltd.
332
p.
43703102
Robinson,
P.
(1995)
Carbaryl:
Magnitude
of
Carbaryl
Residue
In/
On
Fresh
Peas:
Final
Report:
Lab
Project
Number:
US94S40R:
44738:
94
0240.
Unpublished
study
prepared
by
Aventis
Ag
Co.
332
p.
43703103
Macy,
L.
(1995)
Carbaryl:
Determination
of
the
Magnitude
of
Residues
on
Pistachios
Treated
with
Foliar
Applications
of
SEVIN
XLR
PLUS
of
Carbaryl
Insecticide:
Final
Report:
Lab
Project
Number:
US94S23R:
44792:
94
0158.
Unpublished
study
prepared
by
Enviro
Bio
Tech,
Ltd.
246
p.
43716601
Singer,
G.
(1995)
Carbaryl:
Magnitude
of
Residues
in/
on
Pasture
Forage
and
Pasture
Hay
Resulting
From
Ground
Applications
of
the
SEVIN
XLR
PLUS:
Final
Report:
Lab
Project
Number:
94S43R:
44654:
94
0329.
Unpublished
study
prepared
by
American
Agricultural
Services,
Inc.
670
p.
116
43721001
Macy,
L.
(1995)
Carbaryl:
Magnitude
of
Residues
in/
on
Broccoli
Resulting
from
Ground
Applications
of
Sevin
XLR
Plus
(1993):
Final
Study
Report:
Lab
Project
Number:
US94S05R:
44799:
94
0051.
Unpublished
study
prepared
by
Aventis
Ag
Co.
and
Colorado
Analytical
&
Development
Corp.
301
p.
43786801
Macy,
L.
(1995)
Carbaryl:
Determination
of
the
Magnitude
of
Residues
on
Almonds
Treated
with
Foliar
Applications
of
SEVIN
XLR
Brand
of
Carbaryl
Insecticide:
Final
Report:
Lab
Project
Number:
US94S19R:
94
0199:
94
0200.
Unpublished
study
prepared
by
Aventis
Ag
Co.
and
Enviro
Bio
Tech,
Ltd.
279
p.
43786802
Lee,
R.
(1995)
SEVIN
XLR
PLUS:
Magnitude
of
Carbaryl
Residues
in/
on
Cucurbit
Vegetable
Raw
Agricultural
Commodities:
Final
Report:
Lab
Project
Number:
44870:
US94S15R:
94
0060.
Unpublished
study
prepared
by
EN
CAS
Analytical
Labs.
552
p.
43786803
Robinson,
P.
(1995)
Determination
of
the
Magnitude
of
Residues
in
Sunflower
Seeds
and
Forage
Treated
with
Foliar
Applications
of
SEVIN
XLR
PLUS
Brand
of
Carbaryl
Insecticide:
Final
Report:
Lab
Project
Number:
44741:
US94S44R:
94
0220.
Unpublished
study
prepared
by
Agri
Business
Group.
311
p.
43786804
Robinson,
P.;
Cappy,
J.
(1995)
Carbaryl:
Magnitude
of
Carbaryl
Residue
in/
on
Dried
Beans:
Final
Report:
Lab
Project
Number:
ML
95
0514
RHP:
44736:
US94S38R.
Unpublished
study
prepared
by
Agri
Business
Group.
341
p.
43786805
Pittman,
J.
(1995)
Radiovalidation
of
the
Method
No.
CARC
0194
Revised
March
27,
1995:
"Carbaryl
Method
for
the
Determination
of
Residue
in
Crop
Samples
by
High
Performance
Liquid
Chromatography":
Final
Report:
Lab
Project
Number:
EC
95
308:
6295:
44789.
Unpublished
study
prepared
by
Aventis
Ag
Co.
107
p.
43786806
Mede,
K.
(1995)
Carbaryl:
Magnitude
of
Residues
in/
on
Cabbage
Resulting
from
Application
of
SEVIN
XLR
PLUS
(1993):
Final
Report:
Lab
Project
Number:
US94S06R:
94
0059:
94
0060.
Unpublished
study
prepared
by
Colorado
Analytical
Research
&
Development
Corp.
326
p.
43793201
Tew,
E.
(1995)
Carbaryl:
Magnitude
of
Residues
in/
on
Grapes
Resulting
from
Ground
Applications
of
Sevin
XLR
Plus
(1994):
Final
Study
Report:
Lab
Project
Number:
44856:
US94S29R:
ML94
0509
RHP.
Unpublished
study
prepared
by
Aventis
Ag
Co.
349
p.
43793202
Ely,
C.
(1995)
Carbaryl:
Magnitude
of
Residues
in
Stone
Fruit
(Cherry,
Peach,
and
Plum)
RAC
Resulting
from
Applications
of
Sevin
XLR
Plus
(1994):
Final
Study
Report:
Lab
Project
Number:
44822:
US94S17R:
94
0123.
Unpublished
study
prepared
by
Aventis
Ag
Co.
and
McKenzie
Labs,
Inc.
495
p.
43794901
Robinson,
P.
(1995)
Carbaryl:
Magnitude
of
Carbaryl
Residues
in/
on
Sorghum:
Final
Report:
Lab
Project
Number:
US94S42R:
44739:
94/
0070.
Unpublished
study
prepared
by
Agri
Business
Group.
592
p.
43794902
Cappy,
J.
(1995)
Carbaryl:
Magnitude
of
Carbaryl
Residues
in/
on
Soybean
and
Processed
Fractions
of
Soybean:
Final
Report:
Lab
Project
Number:
US94S33R:
44880:
1258/
US94S33R.
Unpublished
study
prepared
by
Colorado
Analytical
&
Development
Corp.
296
p.
117
43794903
Mede,
K.
(1995)
Carbaryl:
Magnitude
of
Residues
in/
on
Mustard
Green
Resulting
from
Ground
Applications
of
Sevin
XLR
Plus
(1993):
Final
Report:
Lab
Project
Number:
US94S07R:
44872:
1230/
US94S07R.
Unpublished
study
prepared
by
Colorado
Analytical
&
Development
Corp.
291
p.
43802101
Hovis,
A.
(1995)
Sevin
XLR
Plus:
Magnitude
of
Carbaryl
Residues
in
Citrus
(Orange,
Grapefruit,
Lemon):
Final
Report:
Lab
Project
Number:
44860:
US94S08R:
94
0075.
Unpublished
study
prepared
by
Aventis
Ag
Co.
and
Enviro
Bio
Tech,
Ltd.
407
p.
43802102
Macy,
L.
(1995)
Carbaryl:
Determination
of
the
Magnitude
of
Residues
on
Pecans
Treated
with
Foliar
Applications
of
Sevin
XLR
Plus
Brand
of
Carbaryl
Insecticide:
Final
Report:
Lab
Project
Number:
44871:
US94S32R:
94
0209.
Unpublished
study
prepared
by
Aventis
Ag
Co.
and
EN
CAS
Analytical
Labs.
303
p.
43802103
Mede,
K.
(1995)
Carbaryl:
Magnitude
of
the
Residues
in/
on
Rice
Resulting
from
Foliar
Applications
of
Sevin
XLR
Plus
(1994):
Final
Report:
Lab
Project
Number:
44853:
US94S24R:
94
0163.
Unpublished
study
prepared
by
Aventis
Ag
Co.
and
EN
CAS
Analytical
Labs.
498
p.
43813601
Kowite,
W.
(1995)
Carbaryl:
Magnitude
of
Residues
in
Root
and
Tuber
Crops
(Garden
Beets,
Carrots,
and
Turnips)
RAC
Resulting
from
Application
of
Sevin
XLR
Plus
Insecticide
(1994):
Final
Report:
Lab
Project
Number:
US94S03R:
44883:
94
0003
CA.
Unpublished
study
prepared
by
Colorado
Analytical
Research
&
Development
Corp.
and
Aventis
Ag
Co.
854
p.
43813602
Cappy,
J.
(1995)
Carbaryl:
Magnitude
of
Carbaryl
Residues
in/
on
Wheat
and
Processed
Fractions
of
Wheat:
Final
Report:
Lab
Project
Number:
US94S36R:
44884:
94
0218.
Unpublished
study
prepared
by
Enviro
Bio
Tech,
Ltd.
and
Aventis
Ag
Co.
267
43813603
Macy,
L.
(1995)
Carbaryl:
Magnitude
of
Residues
in
Processed
Rice
Fractions
Resulting
from
Applications
of
Sevin
XLR
Plus
(1994):
Final
Report:
Lab
Project
Number:
US94S26R:
44889:
RP
04
95.
Unpublished
study
prepared
by
Enviro
Bio
Tech,
Ltd.
and
Aventis
Ag
Co.
187
p.
43813604
Cappy,
J.
(1995)
Carbaryl:
Magnitude
of
Carbaryl
Residues
in/
on
Grain
Sorghum
and
Processed
Fractions
of
Grain
Sorghum:
Final
Report:
Lab
Project
Number:
US94S35R:
44892:
94
0217.
Unpublished
study
prepared
by
Aventis
Ag
Co.
and
Colorado
Analytical
Research
&
Development
Corp.
270
p.
43818901
Macy,
L.
(1995)
Carbaryl:
Determination
of
the
Magnitude
of
Residues
on
Walnuts
Treated
with
Foliar
Applications
of
SEVIN
XLR
Plus
Brand
of
Carbaryl
Insecticide:
Final
Report:
Lab
Project
Number:
US94A31R:
94
0204:
94
0205.
Unpublished
study
prepared
by
EN
CAS
Analytical
Labs.
295
p.
43845205
Robinson,
P.
(1995)
Determination
of
the
Magnitude
of
Residues
in
Sunflower
Seed
Processed
Fractions
Treated
with
Foliar
Applications
of
SEVIN
XLR
Plus
Brand
Carbaryl
Insecticide:
Final
Report:
Lab
Project
Number:
44735:
US94S37R:
94
0219.
Unpublished
study
prepared
by
Agri
Business
Group.
484
p.
43850901
Lee,
R.
(1995)
Sevin
XLR
Plus:
Magnitude
of
Carbaryl
Residue
in/
on
Cottonseed
and
Processed
Fractions
of
Cottonseed:
Final
Report:
Lab
Project
Number:
US94S25R:
44875:
94
0162.
Unpublished
study
prepared
by
Aventis
Ag
Co.
390
p.
118
43850902
Shults,
J.
(1995)
Storage
Stability
of
Carbaryl
on
Frozen
Raw
Agricultural
Commodity
Substrates
and
Selected
Processing
Fractions:
Final
Report:
Lab
Project
Number:
US94S47R:
U:\
RHONE\
94S47RFR.
DOC.
Unpublished
study
prepared
by
McKenzie
Labs,
Inc.
276
p.
43915201
Cappy,
J.
(1995)
Carbaryl:
Magnitude
of
Carbaryl
Residue
in/
on
Field
Corn
and
Processed
Fractions
of
Field
Corn:
Final
Report:
Lab
Project
Number:
US94S34R:
44944:
1272.
Unpublished
study
prepared
by
Rhone
Poulenc
Ag
Co.
309
p.
43975601
Ely,
C.
(1996)
SEVIN
XLR
PLUS:
Magnitude
of
Carbaryl
Residues
in/
on
Wheat
Grain:
Final
Report:
Lab
Project
Number:
US95S10R:
45031:
95
0126.
Unpublished
study
prepared
by
Aventis
Ag
Co.
315
p.
43982801
Lee,
R.
(1996)
Determination
of
the
Magnitude
of
Residues
on
Flax
Seed
and
Straw
Treated
with
Foliar
Applications
of
SEVIN
XLR
Plus
Brand
of
Carbaryl
Insecticide:
Final
Study
Report:
Lab
Project
Number:
US95S12R:
45045:
1278.
Unpublished
study
prepared
by
Agvise
Laboratories;
Agri
Business
Group;
and
Colorado
Analytical
Research
and
Development.
240
p.
43984701
Hovis,
A.
(1996)
Sevin
XLR
Plus:
Magnitude
of
Carbaryl
Residues
in/
on
Succulent
Beans:
Final
Report:
Lab
Project
Number:
US95S14R:
45044:
95
0258.
Unpublished
study
prepared
by
McKenzie
Labs,
Inc.;
Agri
Business
Group,
Inc.;
and
Aventis
Ag
Co.
273
p.
43996101
Macy,
L.
(1996)
Magnitude
of
Residues
in/
on
Tomatoes
Resulting
from
Foliar
Applications
of
Sevin
XLR
Plus
(1995):
Final
Report:
Lab
Project
Number:
US95S05R:
95
0149:
95
0150.
Unpublished
study
prepared
by
McKenzie
Laboratories.
323
p.
44019701
Macy,
L.
(1995)
Carbaryl:
Magnitude
of
Residues
in/
on
Broccoli
Resulting
from
Ground
Applications
of
Sevin
XLR
Plus
(1993):
Amended
Final
Report:
Lab
Project
Number:
US94SO5R:
44799:
1231/
US94SO5R.
Unpublished
study
prepared
by
Colorado
Analytical
Research
and
Development
Corporation:
Aventis
Ag
Co.:
and
Agvise
Lab.
303
p.
44046101
Chancey,
E.
(1996)
Carbaryl
Residues
in
Processed
Peanut
Fractions:
Final
Study
Report:
Lab
Project
Number:
US95S03R:
45070:
95
0161.
Unpublished
study
prepared
by
Texas
A&
M
University
Food
Protein
R&
D
Center
and
Colorado
Analytical
R&
D
Corp.
234
p.
44058001
Chancey,
E.
(1996)
Sevin
XLR
Plus:
Magnitude
of
Carbaryl
Residues
in/
on
Field
Corn
Raw
Agricultural
Commodities:
Final
Report:
Lab
Project
Number:
US95S01R:
45068:
95
0117.
Unpublished
study
prepared
by
Colorado
Analytical
Research
and
Development
Corp.
and
Aventis
Ag
Co.
356
p.
44058101
Kowite,
W.
(1996)
Carbaryl:
Magnitude
of
Residues
in
or
on
Sweet
Corn
RAC
Resulting
from
Application
of
Sevin
XLR
Plus
Insecticide
(1995):
Final
Report:
Lab
Project
Number:
US95S13R:
45099:
95
0195.
Unpublished
study
prepared
by
Aventis
Ag
Co.
303
p.
Relates
to
L0000109.
44065901
Norris,
F.
(1996)
Carbaryl:
Magnitude
of
Residues
in/
on
Rangeland
Forage
Resulting
from
an
Aerial
Application
of
Sevin
4
Oil
ULV:
Lab
Project
Number:
US95S02R:
45095:
95
0037.
Unpublished
study
prepared
by
Diamond
Ag
Research;
Midwest
Research,
Inc.;
and
Agvise
Labs.,
Inc.
270
p.
44068401
Norris,
F.
(1996)
Carbaryl:
Freezer
Storage
Stability
of
Carbaryl
in/
on
Selected
Agricultural
Commodities:
Lab
Project
Number:
US95S15R:
45112:
ML95
0570
RHP.
Unpublished
study
prepared
119
by
Colorado
Analytical
Research
&
Development
Corp.;
Enviro
Bio
Tech,
Ltd.;
Morse
Laboratories,
Inc.
433
p.
44072901
Mede,
K.
(1996)
Carbaryl:
Magnitude
of
Residues
in/
on
Pome
Fruit
Resulting
from
Foliar
Applications
of
SEVIN
XLR
Plus
(1995):
Final
Report:
Lab
Project
Number:
US95S06R:
45101:
95
0141.
Unpublished
study
prepared
by
McKenzie
Labs.
293
p.
(Relates
to
L0000110).
44114301
O'Neal,
S.;
Bentley,
W.
(1996)
Identification
of
the
Pyrolysis
Products
of
(carbon
14)
Carbaryl
in
Cigarette
Smoke:
(Final
Report):
Lab
Project
Number:
984:
1912:
EC
95
326.
Unpublished
study
prepared
by
PTRL
East,
Inc.
128
p.
44123101
Dorschner,
K.
(1996)
Carbaryl:
Magnitude
of
the
Residue
on
Okra
Fruit
(Pods):
(Final
Report):
Lab
Project
Number:
05772:
PR
05772:
5772.95
FL25.
Unpublished
study
prepared
by
North
Carolina
State
University;
University
of
Florida;
and
USDA/
ARS
SARL.
436
p.
44145201
Dorschner,
K.
(1996)
Carbaryl:
Magnitude
of
the
Residue
on
Prickly
Pear
Cactus
Fruit
and
Pads:
Lab
Project
Number:
5146:
05146:
PR
05146.
Unpublished
study
prepared
by
Herbicide
Science
Agriculture
Foundation
and
Food
and
Environmental
Toxicology
Lab.,
University
of
Florida.
261
p.
44155401
Nandihalli,
U.
(1996)
Independent
Laboratory
Validation
of
a
Method
for
the
Determination
of
Residues
of
Carbaryl
in
Crop
Samples:
Final
Report:
Lab
Project
Number:
CHW
6224
233:
45151:
11642.
Unpublished
study
prepared
by
Corning
Hazleton,
Inc.
71
p.
44211801
Ely,
C.
(1997)
Sevin
XLR
Plus:
Magnitude
of
Carbaryl
Residues
in/
on
Oranges
Grown
in
EPA
Region
10:
Final
Report:
Lab
Project
Number:
US95S11R:
45202:
1282.
Unpublished
study
prepared
by
Aventis
Ag
Co.
299
p.
(Relates
to
L0000142).
44250301
Hunt,
T.
(1997)
Sample
Storage
Intervals
and
Conditions
Data
to
Support
MRIDs
42883102,
42883103,
42883104:
(Magnitude
of
Residues
of
Carbaryl):
Final
Report:
Lab
Project
Number:
45268.
Unpublished
study
prepared
by
Aventis
Ag
Co.
17
p.
44250901
Lee,
R.
(1997)
Carbaryl:
Magnitude
of
Residues
in
Milk
and
Tissues
of
Lactating
Dairy
Cows:
Final
Report:
Lab
Project
Number:
96S06298:
45266:
96139B.
Unpublished
study
prepared
by
Southwest
Bio
Labs,
Inc.;
Colorado
Analytical
Research
and
Development;
and
Aventis
Ag
Co.
1270
p.
(Relates
toL0000170).
{OPPTS
860.1480}.
44284701
Macy,
L.
(1997)
Sevin
80WSP:
Magnitude
of
Carbaryl
Residues
in/
on
Stone
Fruit
(Cherry,
Peach,
and
Plum)
RAC
in
California:
Final
Report:
Lab
Project
Number:
96S10562:
45306:
10562
01.
Unpublished
study
prepared
by
Aventis
Ag
Co.
372
p.
44286901
Ibrahim,
A.
(1997)
Carbaryl
Validation
of
Method
of
Analysis
for
Free
and
Conjugated
Carbaryl,
5,6
Dihydro
5,6
dihydroxy
Carbaryl
and
5
Methoxy
6
hydroxy
Carbaryl
in
Egg,
Milk,
Poultry,
and
Animal
Tissues:
Final
Report:
Lab
Project
Number:
EC
96
349:
45319:
45186.
Unpublished
study
prepared
by
Aventis
Ag
Co.
300
p.
{OPPTS
860.1340}
120
44286902
Curti,
J.;
Keller,
G.
(1997)
Independent
Laboratory
Validation
of
a
Method
for
the
Determination
of
Free
and
Conjugated
Carbaryl,
5,6
Dihydro
5,6
dihydroxy
Carbaryl,
and
5
Methoxy
6
hydroxy
Carbaryl
in
Egg,
Milk,
and
Beef
Liver:
Final
Report,
:
Lab
Project
Number:
6224
237:
EC
97
365.
Unpublished
study
prepared
by
Covance
Labs,
Inc.
155
p.{
OPPTS
860.1340}
44286903
Ibrahim,
A.
(1997)
Method
of
Analysis
for
the
Determination
of
Free
and
Conjugated
Carbaryl,
5,6
Dihydro
5,6
dihydroxy
Carbaryl,
and
5
Methoxy
6
hydroxy
Carbaryl
and
Egg,
Milk,
Poultry
and
Animal
Tissues:
Revised:
Lab
Project
Number:
45321.
Unpublished
study
prepared
by
Aventis
Ag
Co.
40
p.
44303101
Lee,
R.
(1997)
Carbaryl
and
Its
Metabolites:
Magnitude
of
Residues
in
Milk
and
Tissues
of
Lactating
Dairy
Cows:
Storage
Stability
(Interim
Report):
Lab
Project
Number:
96S12035:
1292:
45132.
Unpublished
study
prepared
by
Colorado
Analytical
Research
and
Development
Corp.
448
p.
44321301
Mede,
K.
(1997)
Carbaryl:
Magnitude
of
Residues
in/
on
Olives
Resulting
from
Foliar
Applications
of
Sevin
80WSP
(1996):
Final
Report:
Lab
Project
Number:
96S10561:
45324:
10561
01.
Unpublished
study
prepared
by
Aventis
Ag
Co.
179
p.
44381901
Lee,
R.
(1997)
Carbaryl
and
Its
Metabolites:
Magnitude
of
Residues
in
Milk
and
Tissues
of
Lactating
Dairy
Cows
Storage
Stability:
Final
Study
Report:
Lab
Project
Number:
45402:
96S12035:
Aventis
1292.
Unpublished
study
prepared
by
Colorado
Analytical
Research
and
Development,
Inc.
466
p.
{OPPTS
860.1380}
44412501
Ely,
C.
(1997)
Sevin
XLR
Plus:
Magnitude
of
Carbaryl
Residues
in/
on
Wheat
Grain:
Amended
Report:
Lab
Project
Number:
US95S10R:
45031:
95
0126.
Unpublished
study
prepared
by
Colorado
Analytical
Research
&
Development
Corp.
and
Agvise
Labs.
359
p.
{OPPTS
860.1500}
| epa | 2024-06-07T20:31:42.228980 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0006/content.txt"
} |
EPA-HQ-OPP-2002-0138-0007 | Supporting & Related Material | "2002-07-31T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
April
28,
2002
MEMORANDUM
SUBJECT:
Carbaryl.
(Chemical
ID
No.
056801/
List
A
Reregistration
Case
No.
0080).
Revised
Dietary
Exposure
Analysis
for
the
HED
Revised
Human
Health
Risk
Assessment.
No
MRID#
DP
Barcode
D281419.
FROM:
Felecia
A.
Fort,
Chemist
Reregistration
Branch
I
Health
Effects
Division
(7509C)
THRU:
Sheila
Piper,
Chemist
and
William
Cutchin,
Chemist
Dietary
Exposure
Science
Advisory
Council
and
Whang
Phang,
Ph.
D.,
Branch
Senior
Scientist
Reregistration
Branch
I
Health
Effects
Division
(7509C)
TO:
Jeffrey
Dawson,
Chemist
Reregistration
Branch
I
Health
Effects
Division
(7509C)
and
Anthony
Britten,
Chemical
Review
Manager
Special
Review
and
Reregistration
Division
(7508C)
The
Health
Effects
Division
(HED)
has
revised
the
acute,
chronic
and
cancer
dietary
risk
analysis
for
the
carbamate
insecticide
carbaryl
in
association
with
the
human
health
risk
assessment
for
the
Reregistration
Eligibility
Decision
Document
(RED).
These
revisions
were
made
to
include
processing
factors
submitted
by
the
registrant;
to
exclude
commodities
that
are
no
longer
supported
and
to
incorporate
revised
acute
and
chronic
Population
Adjusted
Doses
(PADs)
and
Q1
*
(cancer)
that
were
selected
by
the
HIARC
and
CARC,
respectively.
Additionally,
in
response
to
comments
from
the
registrant,
the
dietary
assessments
include
both
the
1989
1992
and
the
1994
1996
consumption
data
(CSFII).
Carbaryl
is
used
on
commodities
in
numerous
crop
groups
in
agricultural
and
home
settings.
A
2
highly
refined
exposure
assessment
is
needed
for
the
RED.
Detailed
usage
information,
monitoring
data,
and
field
trial
data
are
described
in
appendices
to
this
review.
Acute
and
chronic
assessments
are
required
as
well
as
cancer
assessments
using
the
Q1
*
approach.
CONCLUSIONS/
SUMMARY
This
is
a
Tier
3/
4
assessment,
which
is
the
most
highly
refined
assessment
that
can
be
conducted
at
this
time.
Changes
in
the
acute
and
chronic
dietary
PADs
as
well
as
the
addition
of
processing
factors
resulted
in
significantly
lower
risk
estimates.
HED
has
provided
revised
anticipated
residues
(ARs)
for
carbaryl
based
on
USDA
Pesticide
Data
Program
(PDP)
and
Food
and
Drug
Administration
(FDA)
monitoring
data
and
field
trial
data
for
the
commodities
listed
in
Table
1a
of
Attachment
1.
In
addition,
separate
acute
assessments
were
conducted
incorporating
the
results
of
the
Carbamate
Market
Basket
Survey
(CMBS)
(Table
1b,
Attachment
1).
At
the
present
time,
information
from
the
industry
sponsored
Carbamate
Market
Basket
Survey
has
not
been
completely
approved
for
use
in
dietary
risk
assessments.
Assessments
which
include
these
data
are
presented
in
this
document
for
comparison.
When
quality
assurance
procedures
have
been
completed,
HED
will
examine
the
database
for
appropriateness
of
inclusion
into
dietary
risk
assessments
for
the
carbamate
pesticides
monitored
in
the
study.
Chronic
Chronic
dietary
risk
estimates
less
than
100%
of
the
cPAD
are
considered
by
HED
to
be
not
of
concern.
Estimated
chronic
dietary
exposures
for
all
population
subgroups
consumed
<1%
of
the
cPAD
and
consequently
are
below
HED's
level
of
concern.
Cancer
The
cancer
dietary
exposure
assessment
was
conducted
using
the
Q
1
*
approach.
The
Q1*
for
carbaryl
is
8.75
X
10
4.
.
Risks
estimates
above
1
x
10
6
are
considered
to
be
of
concern.
Results
indicate
a
maximum
lifetime
risk
of
2.8
X
10
8
for
the
general
US
population.
Acute
Estimated
acute
dietary
exposure
at
the
99.9th
percentile
of
exposure
exceeds
HED's
level
of
concern
for
some
population
subgroups
when
CMBS
data
are
not
used
and
are
not
of
concern
when
the
CMBS
results
are
incorporated.
The
acute
dietary
assessment
when
CMBS
data
are
not
used
resulted
in
risk
estimates
greater
than
100%
of
the
acute
Population
Adjusted
Dose
(aPAD)
for
all
infants
(<
1
years
old)
and
children
(1
6
years
old)
at
the
99.9th
percentile
of
exposure.
The
highest
exposed
subpopulation
incorporating
all
commodities
using
PDP
and
FDA
monitoring
data
was
all
infants
which
consumed
133%
of
the
aPAD.
When
CMBS
data
was
incorporated,
highest
exposed
subpopulation
was
children
(1
6
years
old)
at
73%
of
the
aPAD.
Although
this
exposure
assessment
is
the
most
refined
carbaryl
assessment
performed
by
HED
to
date,
there
are
several
uncertainties
associated
with
this
assessment
which
are
noted
in
the
Characterization/
Uncertainties
section
of
this
document.
3
Revisions
Made
to
the
Carbaryl
Dietary
Assessment
This
revised
carbaryl
dietary
assessment
included
changes
made
as
a
result
of
registrant
comments
and
additional
data
that
were
submitted
to
the
Agency.
Uses
deleted
The
following
uses
which
are
no
longer
being
supported
by
the
registrant
were
deleted
from
the
dietary
assessment:
dermal
use
on
poultry
and
in
poultry
houses,
and
the
uses
on
barley,
oats,
rye,
and
cottonseed.
Processing,
cooking
and
washing
factors
The
registrant
also
submitted
processing,
cooking
and
washing
factors
which
were
incorporated
into
the
dietary
assessment
(Table
1).
Some
washing
factors
such
as
those
provided
for
broccoli,
cauliflower,
grapes,
orchard
fruit,
spinach,
but
were
not
used
when
PDP
or
CMBS
data
were
used
since
the
residues
reflect
commodities
that
have
been
washed
before
analysis.
Additionally,
canning
and
cooking
factors
for
green
beans,
tomatoes,
and
spinach
were
not
used
since
processed
PDP
data
were
already
available
and
used
in
the
assessment.
Table
1.
Processing
Factors
(bolded
commodities
denotes
change
from
prior
assessment)
Commodity
Type
Factor
Used
for
Apple
Juice
Drying
0.37
2.58
Pear
juice
apple,
pear,
dried
Cabbage
Cooking
Washing
0.1
0.25
cabbage,
Brussels
sprouts,
kohlrabi,
cooked
cabbage,
Brussels
sprouts,
kohlrabi,
washed
Grapefruit
Peel
1.13
Grapefruit
peel
Lemon
Peel
1.16
Lemon
peel
Orange
Peel
1.27
Orange
peel
Corn
Grain
oil
0.25
Corn
oil
Grapes
unprocessed
raisins
processed
raisins
2.17
1.37
Grapes
raisins
Olive
oil
0.81
Olive
oil
Okra
Cooking
Cooking/
steaming
Washing
0.66
0.18
0.28
Okra
Peas
Cooking/
boiling
Washing
0.15
0.30
Peas
cooked
Peanuts
oil
0.29
Peanut
oil
Pineapple
flesh
0.
54
Pineapple
peeled
fruit
Pineapple
juice
Plums
dried
washed
0.15
0.26
Plums(
prunes)
Plums
fresh
Commodity
Type
Factor
Used
for
4
Potatoes
dried
fried
baked
boiled
0.4
0.04
1.2
2.5
Potatoes,
dried
Potatoes,
fried
Potatoes,
baked
Potatoes,
boiled
Rice
polished
bran
0.03
0.4
Rice,
white
Rice,
bran
Soybean
oil
0.005
Soybean
oil
Sugarbeets
sugar
molasses
0.04
0.04
Sugarbeets
Sugarbeets
molasses
Sunflowers
oil
0.03
Sunflowers
oil
Tomatoes
puree
juice
dry
0.65
0.52
0.52
Tomatoes
puree,
paste,
catsup
Tomatoes
juice
Tomatoes,
dried
Wheat
Flour
Germ
Bran
0.10
0.65
1.03
Wheat
flour
Wheat
germ
Wheat
Bran
Almonds
The
dietary
assessment
for
almond
nutmeat
erroneously
used
the
almond
hulls
residue
information.
The
anticipated
residues
were
recalculated
using
the
data
shown
in
Table
2
and
resulted
in
the
following
residue
distribution
files
and
chronic
AR.
Residue
Distribution
File
for
Acute
Assessment
Almonds
FT
15
samples
RDF
#
68
Almonds
FT
4%
CT
Totalz=
360
Totalnz=
15
0.0614
0.0704
0.0786
0.0822
0.0826
0.0932
0.0304
0.0358
0.0380
0.0704
0.0800
0.0840
0.01
0.0300
0.0384
Chronic
AR
=
0.059
ppm
Table
2
.
Residues
of
carbaryl
in/
on
almond
nutmeats
harvested
14
days
following
three
applications
of
the
4
lb/
gal
FlC
formulation
at
5.0
lb
ai/
A/
application
(
15.0
lb
ai/
A/
season).
5
RAC
Test
Location
(county,
state)
Total
Application
Rate
(lb
ai/
A)
Carbaryl
Residues
(ppm)
a
Almond
nutmeats
Butte,
CA
14.9
0.
0614,
0.0704,
0.0786
Fresno,
CA
14.9
0.
0822,
0.0826,
0.0932
Fresno,
CA
14.9
0.
0304,
0.0358,
0.0380
Stanislaus,
CA
15.8
0.
0704,
0.0800,
0.0840
Madera,
CA
15.2
<0.02,
0.0300,
0.0384
Peaches
Single
Serving
Peach
PDP
Data
from
the
year
2000
were
used
for
non
blended
peach
food
forms
where
HED
previously
used
data
that
had
been
decomposited
(Allender
method).
The
resultant
RDF
file
is
shown
below.
Five
hundred
and
thirty
four
samples
were
analyzed;
carbaryl
was
detected
in
79
of
those
samples.
Peaches
(not
blended)
PDP
Single
Serving
2000
534
samples/
79
detects
18%
CT
15%
detected
Residues
ranged
from
0.01
2.7
ppm
RDF
#
60
Peaches
PDP
single
serving
18%
CT
15%
detected
Totalz=
438
Totalnz=
79
17,
0.003
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.011
0.022
0.025
0.026
0.03
0.031
0.031
0.041
0.042
0.046
0.049
0.051
0.052
0.054
0.057
0.06
0.065
0.071
0.073
0.083
0.087
0.094
0.1
0.11
0.11
0.12
0.13
0.14
0.14
0.15
0.15
0.15
0.15
0.15
0.16
0.16
0.18
0.2
0.21
0.24
0.25
0.29
0.34
0.37
0.41
0.49
0.5
0.51
0.54
0.56
0.58
0.59
0.76
0.94
0.94
1.2
1.5
2.7
Toxicology
Information
The
HED
Hazard
Identification
Assessment
Review
Committee
(HIARC)
on
February
19,
6
2002
reevaluated
the
toxicology
data
base
of
carbaryl
and
selected
toxicology
endpoints
for
chronic
and
acute
dietary
as
well
as
occupational
exposure
risk
assessments.
The
selected
toxicological
endpoints
and
the
doses
for
risk
assessment
and
additional
relevant
details
are
summarized
in
Table
3.
On
November
7,
2001,
the
CARC
reconsidered
the
cancer
classification
of
carbaryl.
In
accordance
with
the
EPA
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(July,
1999),
the
CARC
classified
carbaryl
into
the
category
"Likely
to
be
carcinogenic
to
humans"
and
recommended
a
low
dose
linear
extrapolation
approach
using
all
dose
levels
for
the
quantification
of
human
cancer
risk
based
on
the
most
potent
vascular
tumors
in
mice.
The
HED
FQPA
Safety
Factor
Committee
(C.
Christensen,
2/
25/
02)
determined
that
when
assessing
acute
and
chronic
dietary
exposures,
the
safety
factor
should
be
reduced
to1x
for
all
population
subgroups.
Table
3:
Carbaryl
Toxicity
Endpoints
EXPOSURE
SCENARIO
Old
RfD
PAD
New
DOSE
(mg/
kg/
day)
New
RfD
PAD
ENDPOINT
STUDY
Acute
Dietary
(all
populations)
aRfD
=
0.03
mg/
kg
aPAD
=
0.003
mg/
kg/
day
NOAEL=
1
mg/
kg
UF
=
100
FQPA
SF
=
1
aRfD
=
0.01
mg/
kg
aPAD
=
0.01
mg/
kg/
day
Alterations
in
FOB
parameters
after
a
single
dose
to
maternal
animals
Acute
neurotoxicity
study
rat
Chronic
Dietary
(all
populations)
cRfD
=
0.01
mg/
kg/
day
cPAD
=
0.001
mg/
kg/
day
NOAEL
=
3.1
mg/
kg/
day
UF
=
300
FQPA
SF
=
1
cRfD
=
0.01
mg/
kg/
day
cPAD
=
0.01
mg/
kg/
day
Decrease
in
brain
cholinesterase
in
females
Chronic
toxicity
dog
Cancer
Q1*
=
1.19
x
10
2
[mg/
kg/
day]
1
n/
a
Q1*
=
8.75
x
10
4
[mg/
kg/
day]
1
Carbaryl
was
classified
as
"likely
to
be
carcinogenic
to
humans"
based
on
an
increased
incidence
of
hemangiosarcomas
in
male
mice
Carcinogenicity
mice
DEEM™
Program
and
Consumption
Information
Carbaryl
acute
and
chronic
dietary
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(DEEM™)
software
Version
7.76,
which
incorporates
consumption
data
from
USDA's
7
Continuing
Surveys
of
Food
Intake
by
Individuals
(CSFII),
1989
1992.
The
1989
92
data
are
based
on
the
reported
consumption
of
more
than
10,000
individuals
over
three
consecutive
days,
and
therefore
represent
more
than
30,000
unique
"person
days"
of
data.
Foods
"as
consumed"
(e.
g.,
apple
pie)
are
linked
to
raw
agricultural
commodities
and
their
food
forms
(e.
g.,
apples
cooked/
canned
or
wheat
flour)
by
recipe
translation
files
internal
to
the
DEEM
software.
Consumption
data
are
averaged
for
the
entire
US
population
and
within
population
subgroups
for
chronic
exposure
assessment,
but
are
retained
as
individual
consumption
events
for
acute
exposure
assessment.
As
requested
by
the
registrant,
separate
assessments
which
shows
the
results
using
the
newer
1994
1998
consumption
data
were
conducted.
For
chronic
exposure
and
risk
assessment,
an
estimate
of
the
residue
level
in
each
food
or
food
form
(e.
g.,
orange
or
orange
juice)
on
the
commodity
residue
list
is
multiplied
by
the
average
daily
consumption
estimate
for
that
food/
food
form.
The
resulting
residue
consumption
estimate
for
each
food/
food
form
is
summed
with
the
residue
consumption
estimates
for
all
other
food/
food
forms
on
the
commodity
residue
list
to
arrive
at
the
total
estimated
exposure.
Exposure
estimates
are
expressed
in
mg/
kg
body
weight/
day
and
as
a
percent
of
the
cPAD.
This
procedure
is
performed
for
each
population
subgroup.
For
acute
exposure
assessments,
individual
one
day
food
consumption
data
are
used
on
an
individual
byindividual
basis.
The
reported
consumption
amounts
of
each
food
item
can
be
multiplied
by
a
residue
point
estimate
and
summed
to
obtain
a
total
daily
pesticide
exposure
for
a
deterministic
(Tier
1
or
Tier
2)
exposure
assessment,
or
"matched"
in
multiple
random
pairings
with
residue
values
and
then
summed
in
a
probabilistic
(Tier
3/
4)
assessment.
The
resulting
distribution
of
exposures
is
expressed
as
a
percentage
of
the
aPAD
on
both
a
user
(i.
e.,
those
who
reported
eating
relevant
commodities/
food
forms)
and
a
per
capita
(i.
e.,
those
who
reported
eating
the
relevant
commodities
as
well
as
those
who
did
not)
basis.
In
accordance
with
HED
policy,
per
capita
exposure
and
risk
are
reported
for
all
tiers
of
analysis.
However,
for
tiers
1
and
2,
significant
differences
in
user
vs.
per
capita
exposure
and
risk
are
identified
and
noted
in
the
risk
assessment.
HED
notes
that
there
is
a
degree
of
uncertainty
in
extrapolating
exposures
for
certain
population
subgroups
from
the
general
U.
S.
population
which
may
not
be
sufficiently
represented
in
the
consumption
surveys,
(e.
g.,
nursing
and
non
nursing
infants
or
Hispanic
females).
Therefore,
risks
estimated
for
these
population
subgroups
were
included
in
representative
populations
having
sufficient
numbers
of
survey
respondents
(e.
g.,
all
infants
or
females,
13
50
years).
Usage
Information
BEAD
provided
information
(F.
Hernandez,
7/
21/
98,
Attachment
9)
on
the
percent
crop
treated
(%
CT).
For
the
chronic
analysis,
the
weighted
average
%CT
was
incorporated;
for
the
acute
analysis,
the
estimated
maximum
%CT
was
used
when
appropriate.
In
acute
analyses
(except
blended
commodities)
the
adjustment
for
%CT
is
incorporated
in
the
residue
distribution
files
(RDFs)
via
addition
of
zero
residue
values
corresponding
to
the
%
of
crop
not
treated.
For
blended/
not
further
processed
commodities
where
monitoring
data
are
available,
the
entire
distribution
of
monitoring
data
with
no
futher
adjustment
for
%CT
were
used.
For
blended/
processed
commodities
where
monitoring
data
are
available
and
for
all
blended
commodities
where
field
trial
data
were
used,
%CT
is
incorporated
into
a
point
estimate.
For
the
chronic
analyses,
the
%CT
is
listed
as
Adjustment
Factor
2
in
the
DEEM
analysis.
8
Use
of
usage
information
for
assessments
incorporating
the
CMBS
are
described
below.
Residue
Data
Tolerances
for
residues
of
carbaryl
are
currently
expressed
in
terms
of
carbaryl
(1
naphthyl
Nmethylcarbamate
including
its
hydrolysis
product
1
naphthol,
calculated
as
carbaryl,
for
most
raw
crop
commodities
[40
CFR
§180.169(
a)].
The
established
tolerances
for
residues
in/
on
pineapples,
pome
fruits,
avocados,
and
fresh
dill
are
expressed
in
terms
of
carbaryl
per
se
[40
CFR
§180.169(
d)
and
(e)].
Tolerances
for
residues
in
livestock
commodities
are
expressed
as
carbaryl,
including
its
metabolites
1
naphthol
(naphthyl
sulfate),
5,6
dihydrodihydroxy
carbaryl,
and
5,6
dihydrodihydroxy
naphthol,
calculated
as
carbaryl
[40
CFR
§180.169(
b)
and
(c)].
A
tolerance
for
residues
in
pineapple
bran
is
expressed
in
terms
of
carbaryl
per
se
[40
CFR
§186.550].
An
interim
tolerance
has
been
established
for
carbaryl
and
its
1
naphthol
metabolite
in
eggs
[40
CFR
§180.319].
For
the
purpose
of
reregistration,
adequate
magnitude
of
the
residue
data
are
available
on
the
following
crops:
alfalfa,
almond,
asparagus,
beans
(dried
and
succulent),
blueberry,
broccoli,
cabbage,
celery,
cherry,
citrus
fruits,
clover,
corn
(sweet
and
field),
cucurbits
(cantaloupes,
cucumbers
and
squash),
cranberry,
flax,
grape,
head
and
leaf
lettuce,
mustard
greens,
okra,
peanut,
peas
(dried
and
succulent),
pecan,
pepper,
pistachio,
pome
fruits,
potato,
prickly
pear
cactus,
raspberry,
rice,
sorghum,
soybean,
spinach,
stone
fruits,
strawberry,
sunflower,
sweet
potato,
tobacco,
tomato,
and
walnut.
Tolerances
of
2
ppm
and
10
ppm
have
been
established
for
residues
of
carbaryl
in
pineapples
and
bananas,
respectively.
The
registrant
intends
to
support
the
tolerances
for
residues
of
carbaryl
in/
on
these
commodities
as
import
tolerances.
Adequate
field
trial
data
depicting
carbaryl
residues
following
applications
made
according
to
the
maximum
or
proposed
use
patterns
have
been
submitted
for
these
commodities.
Geographical
representation
is
adequate
and
a
sufficient
number
of
trials
reflecting
representative
formulation
classes
were
conducted.
Carbaryl
residues
were
<LOQ
in/
on
sweet
potato,
sugar
beets,
corn
grain,
flax
seed,
and
peanuts.
Quantifiable
residues
were
detected
in
all
other
raw
agricultural
commodities
(RACs).
For
a
given
crop,
residue
levels
were
quite
variable
overall,
probably
owing
to
climactic
variations,
but
were
generally
consistent
within
any
specific
field
trial
location.
Anticipated
residue
estimates
are
presented
in
Table
1a
of
Attachment
1
of
this
document.
In
general
PDP
data
were
used
if
available.
Alternatively,
FDA
surveillance
monitoring
data
from
the
years
1992
98
were
used
if
sufficient
samples
were
available.
Finally,
data
from
crop
field
trials
were
used
if
there
were
insufficient
PDP
or
FDA
monitoring
data.
Adequate
PDP
monitoring
data
are
available
for
the
following
commodities:
potatoes,
carrots,
sweet
potato,
celery,
spinach,
lettuce
(head),
broccoli,
succulent
peas
(processed)
,
succulent
beans,
soybean,
tomatoes,
cantaloupe,
winter
squash,
orange,
orange
juice,
apple,
apple
juice,
pear,
peach,
wheat,
sweet
corn,
banana,
grape,
grape
juice
and
milk.
FDA
monitoring
data
were
used
for
the
commodities,
lettuce
(leaf),
cabbage,
eggplant,
succulent
peas
(fresh),
non
bell
pepper,
bell
pepper,
cucumber,
watermelon,
summer
squash,
cherries,
raspberry,
blueberry,
asparagus,
cranberry,
pineapple,
and
strawberry.
Monitoring
data
were
translated
to
similar
crops
when
possible,
generally
according
to
the
HED
SOP
99.3
"Translation
of
Monitoring
Data".
See
Table
1a
of
Attachment
1
for
translations.
Monitoring
data
from
the
years
1994
through
1998
(PDP)
and
the
years
1992
through
1998
(FDA)
were
considered.
Field
trial
data
were
used
for
the
commodities,
garden
beets,
turnips,
mustards,
dried
beans,
dried
peas,
9
almonds,
pecans,
walnuts,
field
corn
grain,
rice,
flax
seed,
okra,
olive,
peanuts,
pistachio,
sugar
beets,
and
sunflower.
For
oysters
and
dill
(fresh),
tolerances
of
2
ppm
and
0.2
ppm,
respectively
was
used
in
the
assessment.
These
data
are
summarized
in
Attachment
1
below.
One
half
the
weighted
average
of
the
limits
of
detection
(LOD)
will
be
used
in
the
dietary
assessment
for
all
treated
non
detectable
(ND)
residues.
Detectable
residues
from
composite
monitoring
data
for
nonblended
food
forms
were
used
to
generate
residue
values
in
single
units
using
the
methods
described
in
the
H.
Allender
paper
dated
5/
26/
99
"Statistical
methods
for
Use
of
Composite
Data
in
Acute
Dietary
Risk
Assessment."
The
"decomposited"
residues
were
then
included
in
residue
distribution
files
(RDF)
for
the
probabilistic
analysis.
Biological
and
Economic
Analysis
Division
(BEAD)
supplied
%CT
which
were
incorporated
into
the
anticipated
residue
or
residue
distribution
file
when
appropriate.
Carbamate
Market
Basket
Survey
(CMBS)
A
separate
dietary
assessment
was
conducted
utilizing
the
CMBS
results.
These
data
are
currently
under
review
by
the
Agency
and
have
not
been
approved
for
use
in
dietary
assessments.
The
CMBS
Task
Force
conducted
a
year
long,
national
survey
of
carbamate
residues
on
selected
food
commodities
purchased
at
grocery
stores.
Residue
data
from
a
market
basket
survey
are
considered
close
approximations
to
residues
potentially
found
at
most
`dinner
plates'
and
is
generally
considered
the
most
appropriate
survey
type
for
use
in
pesticide
risk
and
exposure
assessment.
The
CMBS
collected
up
to
400
single
serve
samples
of
8
different
crops
(apple,
banana,
broccoli,
grape,
lettuce,
orange,
peach
and
tomato).
These
data
are
used
in
the
acute
dietary
analysis
directly
via
RDFs
incorporating
%CT
for
all
food
forms
considered
to
be
partially
or
not
blended.
For
blended
commodities,
the
entire
distribution
of
data
with
no
further
adjustment
for
%CT
was
done.
If
CMBS
data
were
not
available,
then
PDP
or
FDA
monitoring
or
field
trial
data
were
used.
CMBS
data
were
translated
to
similar
commodities
when
feasible
(Table
1b,
Attachment
1);
however,
if
PDP
monitoring
data
were
available
for
the
processed
commodity,
then
CMBS
data
were
not
translated
(i.
e.,
PDP
orange
juice
data
were
used
instead
of
CMBS
data
for
oranges).
The
RDFs
are
shown
in
Attachment
1
of
this
document.
Processing
Factors
Most
of
the
carbaryl
processing
factors
(see
Table
1)
were
obtained
from
processing
studies
submitted
by
the
registrant
either
in
response
to
the
preliminary
dietary
risk
assessment
or
those
compiled
in
a
memo
entitled
"Carbaryl
Anticipated
Residues
for
Carcinogenic
Dietary
Risk
Assessment",
S.
Hummel,
12/
3/
93.
The
rice
processing
factors
were
from
a
review
by
Thurston
Morton
(D216242,
9/
17/
98).
Default
processing
factors
were
maintained
for
all
commodities
not
included
in
Table
1
in
this
document.
Results
This
is
a
Tier
3/
4
assessment,
which
is
the
most
highly
refined
assessment
that
can
be
conducted
at
this
time.
Processing
factors
have
been
incorporated
to
the
fullest
extent
possible.
A
sensitivity
analysis,
setting
all
non
detectable
residue
values
to
zero
was
conducted
to
test
the
relative
contribution
of
1/
2
LOD
residues
to
the
dietary
risk.
These
results
are
based
on
1989
to
92
consumption
data.
When
the
assessments
were
done
using
the
1994
1998
consumption
data,
no
significant
differences
in
dietary
exposure
were
found.
10
HED
has
provided
revised
anticipated
residues
(ARs)
for
carbaryl
based
on
USDA
PDP
and
FDA
monitoring
data,
field
trial
data,
and
CMBS
data
for
the
commodities
listed
in
Table
1a
and
1b
of
Attachment
1.
Chronic
Chronic
dietary
risk
estimates
less
than
100%
of
the
cPAD
are
not
of
concern.
Carbaryl
estimated
dietary
exposure
to
the
general
US
population
and
all
population
subgroups
consumed
<1%
of
the
cPAD
and
are
therefore
not
of
concern.
(Table
4
and
Attachment
2).
Cancer
The
cancer
dietary
exposure
assessment
was
conducted
using
the
Q
1
*
approach.
The
Q1*
for
carbaryl
is
8.75
X
10
4.
.
Risks
estimates
above
1
x
10
6
are
considered
to
be
of
concern.
Results
indicate
a
maximum
lifetime
risk
of
2.8
x
10
8
for
the
general
U.
S.
population.
(Table
4
and
Attachment
2).
1
aPAD/
cPAD
=
acute/
chronic
Population
Adjusted
Dose
=
Acute
or
Chronic
RfD
FQPA
Safety
Factor
11
Table
4.
Results
of
the
Carbaryl
Chronic
and
Cancer
Dietary
Analyses.
Chronic
Pop.
Subgroup
1989
92
1994
1998
Exposure
(mg/
kg/
day)
%
cPAD
Exposure
(mg/
kg/
day)
%
cPAD
Gen.
Population
0.000032
<1
0.000035
<1
All
Infants
0.000054
<1
0.000059
<1
Children
1
6
years
0.
000057
<1
0.000074
<1
Children
7
12
years
0.
000036
<1
0.000034
<1
Females
13
50
years
0.
000026
<1
0.000028
<1
Males
13
19
years
0.
000022
<1
0.000026
<1
Males
20+
years
0.
000031
<1
0.000032
<1
Seniors
55+
0.000031
<1
0.000030
<1
Cancer
Exposure
(mg/
kg/
day)
Lifetime
risk
Gen.
Population
0.000032
2.8
x
10
8
0.000035
3.04
X
10
8
Acute
The
acute
dietary
assessment
resulted
in
risk
estimates
greater
than
100%
of
the
acute
Population
Adjusted
Dose
(aPAD)
for
the
population
subgroups,
all
infants
and
children
(1
to
6
years
old)
at
the
99.9th
percentile
of
exposure
(Table
5).
The
highest
exposed
subpopulation
using
PDP
and
FDA
monitoring
data
was
all
infants
at
133%
of
the
aPAD.
When
CMBS
data
are
incorporated,
the
acute
risk
estimates
are
below
the
Agency's
level
of
concern
(<
100%
aPAD
1
)
at
the
99.9
th
exposure
percentile
for
the
general
U.
S.
population
(46%
of
the
aPAD)
and
all
population
subgroups
(Table
6).
The
acute
dietary
exposure
estimates
for
the
highest
exposed
population
subgroups,
all
infants
(<
1
years
old)
and
children
are
73%
of
the
aPAD.
Peaches
and
apples
were
found
to
be
the
most
significant
contributor
to
the
risk
estimate.
(Attachments
3,
6,
7
and
8).
Characterization/
Uncertainties
of
the
Risk
Estimates
°
No
detectable
residues
were
found
in/
on
several
commodities:
carrots,
chicory,
flax
seed,
horseradish,
parsnip,
salsify,
potato,
celery,
canned
spinach,
head
lettuce,
leaf
lettuce,
rhubarb,
sugarbeets,
Swiss
chard,
Brussels
sprouts,
cabbage,
kohlrabi,
soybean,
corn,
banana,
peanuts,
meat,
meat
fat,
and
milk.
Sensitivity
analyses
conducted
by
eliminating
crops
where
no
detectable
residues
were
found
showed
that
risk
estimates
were
not
significantly
affected
by
assuming
zero
12
in
place
of
1/
2
LOD
on
samples
reported
as
ND.
(Attachments
5).
°
The
consumption
database
used
in
the
dietary
exposure
analysis,
CSFII
1989
1992,
has
a
limited
number
of
individuals
for
the
age
group
infants
less
than
one
year
old.
The
USDA
has
conducted
the
Supplemental
Children's
Survey
(approximately
5000
children)
which
will
be
available
for
use
in
the
near
future.
°
The
results
of
the
Critical
Exposure
Contribution
analysis
showed
that
peaches
and
apples
comprised
a
large
percentage
of
the
residues
found
in
the
tail
end
of
acute
exposure
(Attachments
4)
for
children
and
infants,
respectively.
°
Detectable
residues
from
composite
monitoring
data
for
non
blended
food
forms
were
used
to
generate
residue
values
in
single
units
using
the
methods
described
in
the
H.
Allender
paper
dated
5/
26/
99
"Statistical
methods
for
Use
of
Composite
Data
in
Acute
Dietary
Risk
Assessment."
The
"decomposited"
residues
were
then
included
in
residue
distribution
files
(RDF)
for
the
probabilistic
analysis.
Although
there
is
a
statistical
basis
for
using
these
data,
some
degree
of
uncertainty
can
be
associated
with
this
method.
13
Table
5.
Results
of
the
Carbaryl
Acute
Dietary
Analyses
(Market
Survey
Data
Not
Included)
All
Commodities
(1989
92
Consumption
Data)
Pop.
Subgroup
99.9
th
Percentile
99
th
Percentile
95
th
Percentile
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Gen.
Population
0.005989
60
0.001381
14
0.000505
5
All
Infants
0.013251
133
0.003683
37
0.000864
9
Children
1
6
0.
010974
110
0.002552
26
0.001309
13
Children
7
12
0.008721
87
0.001644
16
0.000722
7
Females
13
50
0.004444
44
0.000918
9
0.
000318
3
Males
13
19
yrs
0.
003596
36
0.000899
9
0.
000428
4
Males
20+
yrs
0.
004223
42
0.000929
9
0.
000318
3
Seniors
55+
yrs
0.005789
58
0.001068
11
0.000307
3
All
Commodities
(1994
98
Consumption
Data)
Pop.
Subgroup
99.9
th
Percentile
99
th
Percentile
95
th
Percentile
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Gen.
Population
0.006150
62
0.001467
15
0.000508
5
All
Infants
0.013420
134
0.004027
40
0.000922
9
Children
1
6
0.
013812
138
0.003282
33
0.001460
15
Children
7
12
0.007073
71
0.001473
15
0.000685
7
Females
13
50
0.004794
48
0.000997
10
0.000322
3
Males
13
19
yrs
0.
005181
52
0.000929
9
0.
000420
4
Males
20+
yrs
0.
003940
39
0.000922
9
0.
000336
3
Seniors
55+
yrs
0.005442
54
0.001003
10
0.000313
3
14
Table
6.
Results
of
the
Carbaryl
Acute
Dietary
Analyses
(Market
Basket
Survey
Data
Included)
All
Commodities
(1989
92
Consumption
Data)
Pop.
Subgroup
99.9
th
Percentile
99
th
Percentile
95
th
Percentile
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Gen.
Population
0.004623
46
0.001241
12
0.000462
5
All
Infants
0.007272
73
0.002875
29
0.000593
6
Children
1
6
0.
007344
73
0.002280
23
0.001241
12
Children
7
12
0.006238
62
0.001345
13
0.000680
7
Females
13
50
0.003546
35
0.000858
9
0.
000299
3
Males
13
19
yrs
0.
002723
27
0.000815
8
0.
000409
4
Males
20+
yrs
0.
003423
34
0.000836
8
0.
000297
3
Seniors
55+
yrs
0.004810
48
0.000905
9
0.
000275
3
All
Commodities
(1994
98
Consumption
data)
Pop.
Subgroup
99.9
th
Percentile
99
th
Percentile
95
th
Percentile
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Gen.
Population
0.004865
49
0.001303
13
0.000465
5
All
Infants
0.008091
81
0.002630
26
0.000650
7
Children
1
6
0.
009481
95
0.002799
28
0.001348
13
Children
7
12
0.004921
49
0.001214
12
0.000643
6
Females
13
50
0.004224
42
0.000878
9
0.
000298
3
Males
13
19
yrs
0.
004515
45
0.000867
9
0.
000402
4
Males
20+
yrs
0.
003359
34
0.000831
8
0.
000311
3
Seniors
55+
yrs
0.004649
46
0.000819
8
0.
000279
3
15
Table
7.
Results
of
the
Carbaryl
Sensitivity
Analyses.
Acute
All
Commodities
at
the
99.9th
percentile
of
exposure
(Market
Basket
Survey
Data
Not
Included)
Pop.
Subgroup
All
commodities
Eliminating
Peaches
Eliminating
Apples
Eliminating
Commodities
with
No
Detectable
Residues
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Gen.
Population
0.005989
60
0.005451
55
0.004943
49
0.005870
59
All
Infants
0.013251
133
0.007188
72
0.011784
118
0.012965
130
Children
1
6
0.
010974
110
0.010164
102
0.008201
82
0.0010765
108
Children
7
12
0.008721
87
0.008243
82
0.006867
69
0.008555
86
Females
13
50
0.004444
44
0.004262
43
0.003890
39
0.004434
44
Males
13
19
yrs
0.
003596
36
0.003535
35
0.003014
30
0.003802
38
Males
20+
yrs
0.
004223
42
0.003949
39
0.003575
36
0.004178
42
Seniors
55+
yrs
0.005789
58
0.005456
55
0.005094
51
0.005703
57
16
Atttachments
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Attachment
2:
Chronic
and
Cancer
Dietary
Exposure
Analysis:
All
Commodities
Attachment
3:
Acute
Dietary
Exposure
Analysis
:
All
Commodities
Attachment
4:
Acute
Critical
Exposure
Contribution
Analysis
Attachment
5:
Acute
Dietary
Exposure
Analysis
:
Excluding
all
Commodities
with
No
detects
Attachment
6:
Acute
Dietary
Exposure
Analysis
:
Excluding
Peaches
Attachment
7:
Acute
Dietary
Exposure
Analysis
:
Excluding
Apples
Attachment
8:
Acute
Dietary
Exposure
Analysis
:
Market
Basket
Survey
All
Commodities
Attachment
9:
Quantitative
Usage
Analysis
(QUA)
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
17
Table
1a:
Summary
of
Anticipated
Residues
for
Carbaryl
(Market
Basket
Data
not
included)
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
Crop
Group
1:
Root
and
Tuber
vegetable
Beets,
garden
(roots)
11
Uncooked
14
Boiled
2
garden
beets
FT
0.024
RDF
#1
NB
17
27
Beets,
garden
(roots)
31
Canned:
NFS
32
Canned:
Cooked
51
Cured:
NFS
(smoked/
pickled/
2
garden
beets
FT
0.024
RDF
#1
PB
17
27
Carrots
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
2
carrots
PDP
0.
0116
RDF
#
2
NB
4
6
Carrots
31
Canned:
NFS
32
Canned:
Cooked
34
Canned:
Boiled
42
Frozen:
Cooked
44
Frozen:
Boiled
2
carrots
PDP
0.0116
RDF
#2
PB
4
6
Horseradish
12
Cooked:
NFS
14
Boiled
2
carrots
PDP
0.
0116
RDF
#3
NB
1
3
2
Horseradish
34
Canned:
Boiled
51
Cured:
NFS
(smoked/
pickled/
2
carrots
PDP
0.
0116
RDF
#3
PB
1
3
2
Parsnips
14
Boiled
2
carrots
PDP
0.
0116
RDF
#3
NB
1
3
2
Potatoes/
white
dry
12
Cooked:
NFS
14
Boiled
15
Fried
31
Canned:
NFS
34
Canned:
Boiled
42
Frozen:
Cooked
2
potato
PDP
0.
0119
PE
=
0.00036
B
2
3
Potatoes/
white
peel
only
13
Baked
15
Fried
2
potato
PDP
0.
0119
RDF
#
4
NB
2
3
Potatoes/
white
peeled
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
2
potato
PDP
0.0119
RDF
#
4
NB
2
3
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
18
32
Canned:
Cooked
34
Canned:
Boiled
42
Frozen:
Cooked
43
Frozen:
Baked
45
Frozen:
Fried
0.0119
RDF
#
4
PB
2
3
Potatoes//
white
unspecified
31
Canned:
NFS
0.
0119
RDF
#
4
PB
2
3
Potatoes/
white
whole
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
2
potato
PDP
0.0119
RDF
#
4
NB
2
3
31
Canned:
NFS
0.
0119
RDF
#
4
PB
2
3
Radishes
11
Uncooked
12
Cooked:
NFS
2
garden
beets
FT
0.024
RDF
#5
PB
1
3
2
Radish,
Chinese
12
Cooked:
NFS
Radishes
oriental
2
garden
beets
FT
0.024
RDF
#5
NB
1
3
2
Rutabagas
Rutabagas
roots
2
turnips
FT
0.121
RDF
#
6
NB
1
3
2
Salsify
(roots)
Salsify(
oyster
plant)
2
carrot
PDP
0.
0116
RDF
#3
NB
1
3
2
Sugar
Beets
(inc.
molasses
98
Refined
0.5
sugar
beets
FT
0.01
0.0004
B
2
4
Sweet
potatoes
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
0.2
sweet
potato
PDP
0.
0065
RDF
#7
NB
18
41
32
Canned:
Cooked
34
Canned:
Boiled
sweet
potato
PDP
0.
0065
RDF
#7
PB
18
41
Turnips,
roots
11
Uncooked
12
Cooked:
NFS
14
Boiled
2
turnips
FT
0.121
RDF
#
6
NB
1
3
2
Crop
Group
2:
Leaves
of
Root
and
Tuber
Vegetables
Beets,
garden
(tops)
11
Uncooked
14
Boiled
75
garden
beets
FT
10.14
RDF
#8
PB
17
27
Radish
Tops
Radishes
tops
75
garden
beets
FT
10.14
RDF
#9
PB
1
3
2
Rutabaga
Tops
12
Cooked:
NFS
75
Turnip
tops
FT
15.3
RDF
#10
PB
1
3
2
Turnips,
tops
14
Boiled
32
Canned:
Cooked
44
Frozen:
Boiled
75
turnip
tops
FT
15.3
RDF
#10
PB
1
3
2
Crop
Group
4:
Leafy
Vegetables
(except
Brassica
Vegetables)
Celery
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
3
Celery
PDP
0.
0152
RDF
#
11
NB
3
6
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
19
31
Canned:
NFS
32
Canned:
Cooked
34
Canned:
Boiled
42
Frozen:
Cooked
3
Celery
PDP
0.
0152
RDF
#
11
PB
3
6
Celery
Juice
31
Canned:
NFS
3
Celery
PDP
0.
0152
RDF
#
11
PB
3
6
Dandelions
11
Uncooked
22
Spinach
PDP
0.
0082
RDF
#
12
PB
1
3
2
Endive
(escarole)
11
Uncooked
12
Cooked:
NFS
10
Leaf
Lettuce
FDA
0.001
RDF
#
15
PB
1
3
2
Lettuce
head
11
Uncooked
10
Lettuce
PDP
0.
0169
RDF
#14
NB
3
8
Lettuce
leaf
11
Uncooked
10
Leaf
Lettuce
FDA
0.
001
RDF
#
15
PB
1
3
2
Lettuce
(unspecified)
31
Canned:
NFS
10
Lettuce
PDP
0.
0169
RDF
#14
PB
3
8
Parsley
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
31
Canned:
NFS
32
Canned:
Cooked
33
Canned:
Baked
34
Canned:
Boiled
22
Spinach
PDP
0.
0082
RDF
#
12
PB
1
3
2
Rhubarb
12
Cooked:
NFS
13
Baked
3
Celery
PDP
0.
015
RDF
#16
NB
1
3
2
43
Frozen:
Baked
3
Celery
PDP
0.
015
RDF
#16
PB
1
3
2
Spinach
11
Uncooked
12
Cooked:
NFS
14
Boiled
42
Frozen:
Cooked
44
Frozen:
Boiled
22
Spinach
PDP
0.
0082
RDF
#
12
PB
1
3
2
31
Canned:
NFS
32
Canned:
Cooked
34
Canned:
Boiled
22
Canned
Spinach
PDP
0.
006
RDF
#13
PB
1
3
2
Swiss
chard
11
Uncooked
14
Boiled
3
Celery
PDP
0.
015
RDF
#
16
NB
1
3
2
Crop
Group
5:
Brassica
Leafy
vegetables
Broccoli
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
10
Broccoli
PDP
0.
013
RDF
#17
NB
4
9
32
Canned:
Cooked
42
Frozen:
Cooked
44
Frozen:
Boiled
10
Broccoli
PDP
0.
013
RDF
#
17
PB
4
9
Brussels
Sprouts
14
Boiled
42
Frozen:
Cooked
10
Cabbage
FDA
0.
001
RDF
#18
PB
33
67
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
20
Cabbage
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
21
Cabbage
FDA
0.
001
RDF
#
19
NB
2
4
31
Canned:
NFS
32
Canned:
Cooked
51
Cured:
NFS
(smoked/
pickled/
21
Cabbage
FDA
0.
001
RDF
#
19
PB
2
4
Cauliflower
11
Uncooked
12
Cooked:
NFS
14
Boiled
15
Fried
10
Broccoli
PDP
0.
013
RDF
#
20
NB
2
4
42
Frozen:
Cooked
10
Broccoli
PDP
0.
012
RDF
#20
PB
2
4
Collards
42
Frozen:
Cooked
10
Mustard
FT
2.78
RDF
#
21
PB
4
10
Kale
12
Cooked:
NFS
14
Boiled
32
Canned:
Cooked
10
Mustard
FT
2.78
RDF
#
22
PB
1
3
2
Kohlrabi
14
Boiled
10
Cabbage
FDA
0.
001
RDF
#
23
NB
1
3
2
Mustard
greens
14
Boiled
10
Mustard
FT
2.78
RDF
#
22
PB
1
3
2
Crop
Group
6:
Legume
Vegetables
(Succulent
or
Dried)
Beans
dry
black
eyed
peas/
cowpea
14
Boiled
1
Dried
Beans
FT
0.067
0.002
B
1
3
Beans
dry
broadbeans
14
Boiled
1
Dried
Beans
FT
0.067
0.002
B
1
3
Beans
dry
garbanzo/
chick
pea
12
Cooked:
NFS
14
Boiled
15
Fried
32
Canned:
Cooked
1
Dried
Beans
FT
0.067
0.002
B
1
3
Beans
dry
great
northern
32
Canned:
Cooked
1
Dried
Beans
FT
0.067
0.002
B
1
3
Beans
dry
hyacinth
1
Dried
Beans
FT
0.067
0.002
B
1
3
Beans
dry
kidney
12
Cooked:
NFS
13
Baked
14
Boiled
32
Canned:
Cooked
34
Canned:
Boiled
42
Frozen:
Cooked
1
Dried
Beans
FT
0.067
0.002
B
1
3
Beans
dry
lima
14
Boiled
32
Canned:
Cooked
1
Dried
Beans
FT
0.067
0.002
B
1
3
Beans
dry
navy
(pea)
32
Canned:
Cooked
34
Canned:
Boiled
1
Dried
Beans
FT
0.067
0.002
B
1
3
Beans
dry
other
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
34
Canned:
Boiled
1
Dried
Beans
FT
0.067
0.002
B
1
3
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
21
Beans
dry
pigeon
beans
1
Dried
Beans
FT
0.067
0.002
B
1
3
Beans
dry
pinto
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
32
Canned:
Cooked
42
Frozen:
Cooked
1
Dried
Beans
FT
0.067
0.002
B
1
3
Beans
broadbeans
10
Succulent
Beans
PDP
.0.023
RDF
#
24
PB
14
21
Beans
succulent
green
11
Uncooked
12
Cooked:
NFS
14
Boiled
10
Succulent
Beans
PDP
.0.023
RDF
#
24
PB
14
21
31
Canned:
NFS
32
Canned:
Cooked
34
Canned:
Boiled
42
Frozen:
Cooked
44
Frozen:
Boiled
51
Cured:
NFS
(smoked/
pickled/
10
Processed
Succulent
Beans
PDP
0.012
RDF
#25
PB
10
16
Beans
succulent
hyacinth
10
Succulent
Beans
PDP
0.
023
RDF
#
24
PB
14
21
Beans
succulent
lima
11
Uncooked
12
Cooked:
NFS
14
Boiled
32
Canned:
Cooked
42
Frozen:
Cooked
44
Frozen:
Boiled
10
Processed
Succulent
Beans
PDP
0.012
RDF
#26
PB
13
30
Beans
succulent
other
34
Canned:
Boiled
10
Processed
Succulent
Beans
PDP
0.012
RDF
#25
PB
10
16
Beans
yellow/
wax
14
Boiled
10
Succulent
Beans
PDP
0.
023
RDF
#
24
PB
14
21
32
Canned:
Cooked
42
Frozen:
Cooked
10
Processed
Succulent
Beans
PDP
0.012
RDF
#25
PB
10
16
Beans
unspecified
10
Succulent
Beans
PDP
0.
0.023
RDF
#
24
PB
14
21
Lentils
14
Boiled
1
Dried
Beans
FT
0.067
0.002
B
1
3
Mung
Bean
(SPROUTS)
11
Uncooked
12
Cooked:
NFS
14
Boiled
15
Fried
1
Dried
Beans
FT
0.067
0.002
B
1
3
Peas
succulent/
black
eyed/
cowpea
12
Cooked:
NFS
14
Boiled
10
Peas
FDA
0.
13
RDF
#
27
PB
2
7
32
Canned:
Cooked
42
Frozen:
Cooked
10
Peas
PDP
0.
0127
RDF
#
28
PB
1
5
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
22
Peas
(garden)
green
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
10
Peas
FDA
0.
13
RDF
#
27
PB
2
7
31
Canned:
NFS
32
Canned:
Cooked
34
Canned:
Boiled
42
Frozen:
Cooked
44
Frozen:
Boiled
45
Frozen:
Fried
10
Peas
PDP
0.
0127
RDF
#
28
PB
1
5
Snowpeas
11
Uncooked
12
Cooked:
NFS
14
Boiled
15
Fried
10
Peas
FDA
0.
13
RDF
#27
PB
1
5
42
Frozen:
Cooked
10
Peas
PDP
0.
0127
RDF
#
28
PB
Peas
(garden)
dry
12
Cooked:
NFS
14
Boiled
31
Canned:
NFS
32
Canned:
Cooked
34
Canned:
Boiled
1
Dry
Peas
FT
0.146
0.013
B
3
9
Soybeans
other
0.
5
Soybeans
PDP
0.0015
0.000015
B
1
1
Soybeans
flour
(defatted)
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
31
Canned:
NFS
34
Canned:
Boiled
42
Frozen:
Cooked
98
Refined
0.5
Soybeans
PDP
0.
0015
0.000015
B
1
1
Soybeans
flour
(full
fat)
12
Cooked:
NFS
13
Baked
14
Boiled
34
Canned:
Boiled
42
Frozen:
Cooked
0.5
Soybeans
PDP
0.
0015
0.000015
B
1
1
Soybeans
flour
(low
fat)
12
Cooked:
NFS
13
Baked
15
Fried
31
Canned:
NFS
0.5
Soybeans
PDP
0.
0015
0.000015
B
1
1
Soybeans
mature
seeds
dry
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
41
Frozen:
NFS
0.5
Soybeans
PDP
0.
0015
0.000015
B
1
1
Soybeans
oil
98
Refined
0.5
Soybeans
PDP
0.
0015
0.000015
B
1
1
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
23
Soybeans
protein
isolate
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
31
Canned:
NFS
32
Canned:
Cooked
33
Canned:
Baked
34
Canned:
Boiled
41
Frozen:
NFS
42
Frozen:
Cooked
51
Cured:
NFS
(smoked/
pickled/
0.5
Soybeans
PDP
0.
0015
0.000015
B
1
1
Soybeans
sprouted
seeds
14
Boiled
0.5
Soybeans
PDP
0.
0015
0.000015
B
1
1
Crop
Group
8:
Fruiting
Vegetables
(except
Cucurbits)
Group
Eggplants
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
5
Sweet
pepper
FDA
0.005
RDF
#
29
NB
9
21
Peppers
chilli
incl
jalapeno
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
5
Hot
Pepper
FDA
0.
108
RDF
#
30
NB
1
3
2
Peppers
chilli
incl
jalapeno
31
Canned:
NFS
32
Canned:
Cooked
33
Canned:
Baked
34
Canned:
Boiled
42
Frozen:
Cooked
51
Cured:
NFS
(smoked/
pickled/
52
Cured:
Cooked(
smokd/
pickld/
60
Canned:
Cured
5
Hot
Pepper
FDA
0.
108
RDF
#
30
PB
1
3
2
Peppers
sweet(
garden)
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
5
Sweet
Pepper
FDA
0.
02
RDF
#
31
NB
13
30
Peppers
sweet(
garden)
31
Canned:
NFS
32
Canned:
Cooked
34
Canned:
Boiled
42
Frozen:
Cooked
51
Cured:
NFS
(smoked/
pickled/
5
Sweet
Pepper
FDA
0.
02
RDF
#
31
PB
13
30
Peppers
Other
11
Uncooked
5
Hot
Pepper
FDA
0.
108
RDF
#
30
NB
1
3
2
Pimiento
12
Cooked:
NFS
14
Boiled
5
Hot
Pepper
FDA
0.
108
RDF
#
30
NB
1
3
2
31
Canned:
NFS
60
Canned:
Cured
5
Hot
Pepper
FDA
0.
108
RDF
#
30
NB
1
3
2
Paprika
12
Cooked:
NFS
5
Hot
Pepper
FDA
0.
108
RDF
#
30
NB
1
3
2
Tomato
Catsup
34
Canned:
Boiled
5
Tomato
PDP
0.
0044
RDF
#
32
PB
15
27
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
24
Tomatoes
dried
12
Cooked:
NFS
15
Fried
5
Tomato
PDP
0.
0044
RDF
#
32
PB
15
27
Tomatoes
juice
31
Canned:
NFS
32
Canned:
Cooked
34
Canned:
Boiled
42
Frozen:
Cooked
5
Tomato
PDP
0.
0044
RDF
#
32
PB
15
27
Tomatoes
paste
14
Boiled
31
Canned:
NFS
32
Canned:
Cooked
33
Canned:
Baked
34
Canned:
Boiled
42
Frozen:
Cooked
5
Tomato
PDP
0.
0044
RDF
#
32
PB
15
27
Tomatoes
puree
12
Cooked:
NFS
14
Boiled
31
Canned:
NFS
32
Canned:
Cooked
33
Canned:
Baked
34
Canned:
Boiled
42
Frozen:
Cooked
5
Tomato
PDP
0.
0044
RDF
#
32
PB
15
27
Tomatoes
whole
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
5
Tomato
PDP
0.
0044
RDF
#
33
NB
5
11
Tomatoes
whole
31
Canned:
NFS
32
Canned:
Cooked
33
Canned:
Baked
34
Canned:
Boiled
42
Frozen:
Cooked
5
Tomato
PDP
0.
0044
RDF
#
32
PB
15
27
Crop
Group
9:
Cucurbit
Vegetables
Cucumbers
11
Uncooked
3
Cucumbers
FDA
0.
0033
RDF
#
34
NB
14
32
34
Canned:
Boiled
60
Canned:
Cured
3
Cucumbers
FDA
0.0033
RDF
#34
PB
14
32
Bitter
melon
12
Cooked:
NFS
3
Cantaloupe
PDP
0.
0056
RDF
#35
NB
1
3
2
Melons
cantaloupes
juice
3
Cantaloupe
PDP
0.
0056
RDF
#
36
PB
7
9
Melons
cantaloupes
pulp
11
Uncooked
3
Cantaloupe
PDP
0.
0056
RDF
#
36
NB
7
9
Melons
Casaba
11
Uncooked
3
Cantaloupe
PDP
0.
0056
RDF
#
35
NB
1
2a
Melons
Crenshaw
3
Cantaloupe
PDP
0.
0056
RDF
#
35
NB
1
2a
Melons
honeydew
11
Uncooked
3
Cantaloupe
PDP
0.
0056
RDF
#
37
NB
19
44
Melons
persian
3
Cantaloupe
PDP
0.
0056
RDF
#35
NB
1
3
2
Watermelon
11
Uncooked
3
Watermelon
FDA
0.
0019
RDF
#38
NB
13
15
Watermelon
juice
3
Watermelon
FDA
0.
0019
RDF
#38
PB
13
15
Wintermelon
14
Boiled
3
Cantaloupe
PDP
0.
0056
RDF
#35
NB
1
3
2
Casabas
11
Uncooked
3
Cantaloupe
PDP
0.
0056
RDF
#35
NB
1
3
2
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
25
Pumpkins
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
3
Winter
Squash
PDP
0.
006
RDF
#
39
NB
31
56
33
Canned:
Baked
34
Canned:
Boiled
3
Winter
Squash
PDP
0.
006
RDF
#
39
PB
31
56
Squash,
winter
(includes
spaghetti
squash)
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
3
Winter
Squash
PDP
0.
006
RDF
#
40
NB
11
27
Squash,
summer
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
3
Summer
Squash
FDA
0.
016
RDF
#
41
NB
11
27
34
Canned:
Boiled
42
Frozen:
Cooked
51
Cured:
NFS
(smoked/
pickled/
3
Summer
Squash
FDA
0.
016
RDF
#
41
PB
11
27
Crop
Group
10:
Citrus
Fruits
Citrus
citron
13
Baked
14
Boiled
10
Orange
PDP
0.
013
RDF
#42
PB
1
3
2
Grapefruit
peel
10
Orange
PDP
0.
013
RDF
#42
PB
4
6
Grapefruit
juice
11
Uncooked
31
Canned:
NFS
10
Orange
juice
PDP
0.
006
RDF
#43
PB
4
6
Grapefruit
juice
concentrate
41
Frozen:
NFS
10
Orange
juice
PDP
0.
006
RDF
#43
PB
4
6
Grapefruit
peeled
fruit
11
Uncooked
12
Cooked:
NFS
10
Orange
PDP
Decomposited
0.013
RDF
#45
NB
4
6
Grapefruit
peeled
fruit
31
Canned:
NFS
10
Orange
PDP
0.
006
RDF
#42
PB
4
6
Kumquats
10
Orange
PDP
0.
013
RDF
#42
PB
1
3
2
Lemons
juice
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
31
Canned:
NFS
32
Canned:
Cooked
34
Canned:
Boiled
41
Frozen:
NFS
42
Frozen:
Cooked
10
Orange
juice
PDP
0.
006
RDF
#44
PB
3
7
Lemons
juice
concentrate
12
Cooked:
NFS
13
Baked
14
Boiled
31
Canned:
NFS
34
Canned:
Boiled
41
Frozen:
NFS
10
Orange
juice
PDP
0.
006
RDF
#44
PB
3
7
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
26
Lemons
peel
11
Uncooked
13
Baked
14
Boiled
31
Canned:
NFS
34
Canned:
Boiled
41
Frozen:
NFS
10
Orange
PDP
0.
013
RDF
#42
PB
3
7
Lemons
peeled
fruit
11
Uncooked
12
Cooked:
NFS
10
Orange
PDP
Decomposited
0.013
RDF
#45
NB
3
7
Lemons
peeled
fruit
31
Canned:
NFS
10
Orange
PDP
0.
013
RDF
#42
PB
3
7
Limes
juice
11
Uncooked
31
Canned:
NFS
32
Canned:
Cooked
34
Canned:
Boiled
41
Frozen:
NFS
10
Orange
juice
PDP
0.
006
RDF
#46
PB
1
3
2
Limes
juice
concentrate
12
Cooked:
NFS
41
Frozen:
NFS
10
Orange
juice
PDP
0.
006
RDF
#46
PB
1
3
2
Limes
peel
13
Baked
14
Boiled
10
Orange
PDP
0.
013
RDF
#42
PB
1
3
2
Limes
peeled
fruit
11
Uncooked
10
Orange
PDP
Decomposited
0.013
RDF
#45
NB
1
3
2
Oranges
juice
11
Uncooked
12
Cooked:
NFS
31
Canned:
NFS
41
Frozen:
NFS
10
Orange
juice
PDP
0.
006
RDF
#47
PB
3
5
Oranges
juice
concentrate
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
31
Canned:
NFS
41
Frozen:
NFS
42
Frozen:
Cooked
10
Orange
juice
PDP
0.
006
RDF
#47
PB
3
5
Oranges
peel
11
Uncooked
12
Cooked:
NFS
31
Canned:
NFS
41
Frozen:
NFS
10
Orange
PDP
0.
013
RDF
#42
PB
3
5
Oranges
peeled
fruit
11
Uncooked
12
Cooked:
NFS
10
Orange
PDP
Decomposited
0.013
RDF
#45
NB
3
5
Oranges
peeled
fruit
31
Canned:
NFS
10
Orange
PDP
0.
013
RDF
#42
PB
3
5
Tangelos
10
Orange
PDP
Decomposited
0.013
RDF
#45
NB
1
3
2
Tangerine
11
Uncooked
10
Orange
PDP
Decomposited
0.013
RDF
#45
NB
1
3
2
31
Canned:
NFS
41
Frozen:
NFS
10
Orange
PDP
0.
013
RDF
#42
PB
1
3
2
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
27
Tangerines
juice
11
Uncooked
31
Canned:
NFS
41
Frozen:
NFS
10
Orange
juice
PDP
0.
006
RDF
#46
PB
1
3
2
Tangerines
juiceconcentrate
10
Orange
juice
PDP
0.
006
RDF
#46
PB
1
3
2
Crop
Group
11:
Pome
Fruits
Group
Apples
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
12
Apple
PDP
Decomposited
0.03
RDF
#
48
NB
23
31
18
Dried
12
Apple
PDP
0.
03
0.
009
B
23
31
31
Canned:
NFS
32
Canned:
Cooked
33
Canned:
Baked
34
Canned:
Boiled
42
Frozen:
Cooked
12
Apple
PDP
0.
03
RDF
#49
PB
23
31
Apples
dried
13
Baked
14
Boiled
18
Dried
42
Frozen:
Cooked
12
Apple
PDP
0.
03
RDF
#49
PB
23
31
Apples
juice/
cider
11
Uncooked
12
Cooked:
NFS
14
Boiled
31
Canned:
NFS
41
Frozen:
NFS
12
Apple
juice
PDP
0.
010
RDF
#50
PB
23
31
Apples
juice
concentrate
12
Cooked:
NFS
13
Baked
31
Canned:
NFS
41
Frozen:
NFS
12
Apple
juice
PDP
0.
010
RDF
#50
PB
23
31
Pears
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
12
Pear
PDP
Decomposite
0.0098
RDF
#51
NB
3
6
31
Canned:
NFS
12
Pear
PDP
0.
0098
RDF
#52
PB
3
6
Pears
dried
13
Baked
14
Boiled
18
Dried
12
Pear
PDP
0.
0098
RDF
#52
PB
3
6
Pears
juice
11
Uncooked
12
Cooked:
NFS
13
Baked
31
Canned:
NFS
33
Canned:
Baked
41
Frozen:
NFS
42
Frozen:
Cooked
12
Pear
PDP
0.
0098
RDF
#52
PB
3
6
Quinces
12
Pear
PDP
0.
0098
RDF
#53
NB
1
3
2
Loquat
12
Pear
PDP
0.
0098
RDF
#53
NB
1
3
2
Crabapples
31
Canned:
NFS
12
Apple
PDP
0.
033
RDF
#54
PB
1
3
2
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
28
Crop
Group
12:
Stone
Fruits
Group
Apricot
juice
11
Uncooked
12
Cooked:
NFS
31
Canned:
NFS
42
Frozen:
Cooked
10
Peaches
PDP
0.
07
RDF
#
55
PB
1
3
2
Apricots
11
Uncooked
12
Cooked:
NFS
14
Boiled
10
Peaches
PDP
0.
07
RDF
#
56
NB
1
3
2
31
Canned:
NFS
34
Canned:
Boiled
10
Peaches
PDP
0.
07
RDF
#
55
PB
1
3
2
Apricots
dried
13
Baked
14
Boiled
18
Dried
10
Peaches
PDP
0.
07
RDF
#
55
PB
1
3
2
Cherries
11
Uncooked
10
Cherries
FDA
0.
127
RDF
#57
PB
25
36
12
Cooked:
NFS
13
Baked
14
Boiled
31
Canned:
NFS
33
Canned:
Baked
41
Frozen:
NFS
10
Cherries
FDA
0.
127
RDF
#58
PB
12
24
Cherries
dried
10
Cherries
FDA
0.
127
RDF
#57
PB
25
36
Cherries
juice
13
Baked
14
Boiled
31
Canned:
NFS
41
Frozen:
NFS
10
Cherries
FDA
0.
127
RDF
#58
PB
12
24
Nectarines
11
Uncooked
10
Peaches
PDP
0.
07
RDF
#59
NB
12
24
Peaches
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
10
Peaches
PDP
0.
07
RDF
#60
NB
15
18
31
Canned:
NFS
41
Frozen:
NFS
10
Peaches
PDP
0.
07
RDF
#61
PB
15
18
Peaches
dried
14
Boiled
18
Dried
10
Peaches
PDP
0.
07
RDF
#61
PB
15
18
Peaches
juice
11
Uncooked
31
Canned:
NFS
10
Peaches
PDP
0.
07
RDF
#61
PB
15
18
Plums
(damsons)
11
Uncooked
12
Cooked:
NFS
10
Peaches
PDP
0.
07
RDF
#
96
NB
5
9
31
Canned:
NFS
42
Frozen:
Cooked
51
Cured:
NFS
(smoked/
pickled/
10
Peaches
PDP
0.
07
RDF
#
62
PB
5
9
Plums/
prune
juice
11
Uncooked
31
Canned:
NFS
10
Peaches
PDP
0.
07
RDF
#
62
PB
5
9
Plums
prunes
(dried)
13
Baked
14
Boiled
18
Dried
31
Canned:
NFS
10
Peaches
PDP
0.
07
RDF
#
62
PB
5
9
Crop
Group
13:
Berries
Group
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
29
Blackberries
11
Uncooked
13
Baked
14
Boiled
31
Canned:
NFS
34
Canned:
Boiled
41
Frozen:
NFS
12
Raspberry
FDA
0.
09
RDF
#
63
PB
28
44
Blackberries
juice
11
Uncooked
31
Canned:
NFS
12
Raspberry
FDA
0.
09
RDF
#63
PB
28
44
Blueberries
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
31
Canned:
NFS
41
Frozen:
NFS
3
Blueberry
FDA
0.
09
RDF
#
64
PB
22
45
Boysenberries
31
Canned:
NFS
34
Canned:
Boiled
41
Frozen:
NFS
12
Raspberry
FDA
0.
09
RDF
#65
PB
1
3
2
Currant
11
Uncooked
3
Blueberry
FDA
0.
09
RDF
#66
PB
1
3
2
Dewberries
Dewberries
12
Raspberry
FDA
0.
09
RDF
#65
PB
1
3
2
Elderberry
Elderberries
3
Blueberry
FDA
0.
09
RDF
#66
PB
1
3
2
Gooseberry
Gooseberries
3
Blueberry
FDA
0.
09
RDF
#66
PB
1
3
2
Huckleberry
Huckleberries
3
Blueberry
FDA
0.
09
RDF
#66
PB
1
3
2
Loganberries
Loganberries
12
Raspberry
FDA
0.
09
RDF
#65
PB
1
3
2
Raspberries
11
Uncooked
13
Baked
14
Boiled
31
Canned:
NFS
34
Canned:
Boiled
41
Frozen:
NFS
12
Raspberry
FDA
0.
09
RDF
#67
PB
4
10
Youngberries
12
Raspberry
FDA
0.
09
RDF
#65
PB
1
3
2
Crop
Group
14:
Tree
Nuts
Almonds
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
18
Dried
41
Frozen:
NFS
0.1
Almond
FT
0.059
RDF
#68
PB
2
4
Chestnuts
14
Boiled
12
Cooked:
NFS
13
Baked
0.1
Almond
FT
0.059
RDF
#69
PB
1
3
2
Filberts
(hazelnuts)
11
Uncooked
13
Baked
14
Boiled
0.1
Pecan
FT
0.022
RDF
#70
PB
4
12
Pecans
11
Uncooked
13
Baked
14
Boiled
0.1
Pecan
FT
0.022
RDF
#71
PB
20
24
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
30
Walnuts
11
Uncooked
12
Cooked:
NFS
13
Baked
1.0
Walnut
FT
0.27
RDF
#72
PB
1
2
Walnut
oil
1.
0
Walnut
FT
0.27
0.0054
B
1
2
Crop
Group
15:
Cereal
Grains
Corn,
fresh
(including
sweet)
K
+
CWHR
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
0.1
Corn
PDP
0.
0085
RDF
#
73
NB
1
1
32
Canned:
Cooked
34
Canned:
Boiled
35
Canned:
Fried
42
Frozen:
Cooked
0.1
Corn
PDP
0.
0085
RDF
#
73
PB
1
1
Corn
grain
endosperm
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
31
Canned:
NFS
32
Canned:
Cooked
33
Canned:
Baked
34
Canned:
Boiled
41
Frozen:
NFS
42
Frozen:
Cooked
43
Frozen:
Baked
45
Frozen:
Fried
99
Alcohol/
Fermented/
Distilled
0.02
Corn
FT
0.01
0.0001
B
11
Corn
grain
oil
98
Refined
0.02
Corn
FT
0.01
0.0001
B
11
Corn
grain
bran
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
31
Canned:
NFS
0.02
Corn
FT
0.01
0.0001
B
11
Corn
grain/
sugar
molasses
12
Cooked:
NFS
41
Frozen:
NFS
0.02
Corn
FT
0.01
0.0001
B
11
Corn
grain/
sugar/
hfcs
98
Refined
0.02
Corn
FT
0.01
0.0001
B
11
Corn,
popcorn
12
Cooked:
NFS
13
Baked
0.02
Corn
FT
0.01
0.0001
B
11
Millet,
proso,
grain
13
Baked
1
Wheat
PDP
0.
0015
0.000015
B
1
1
Rice
milled
(white)
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
31
Canned:
NFS
32
Canned:
Cooked
34
Canned:
Boiled
42
Frozen:
Cooked
99
Alcohol/
Fermented/
Distilled
15
Rice
FT
7.4
0.
074
B
1
1
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
31
Rice
bran
11
Uncooked
12
Cooked:
NFS
13
Baked
15
Fried
31
Canned:
NFS
15
Rice
FT
7.4
0.
074
B
1
1
Rice
rough
(brown)
12
Cooked:
NFS
13
Baked
14
Boiled
99
Alcohol/
Fermented/
Distilled
15
Rice
FT
7.4
0.
074
B
1
1
Sorghum,
grain
14
Boiled
10
Wheat
PDP
0.
0015
0.000015
B
1
1
Wheat
flour
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
31
Canned:
NFS
32
Canned:
Cooked
33
Canned:
Baked
34
Canned:
Boiled
41
Frozen:
NFS
42
Frozen:
Cooked
43
Frozen:
Baked
45
Frozen:
Fried
52
Cured:
Cooked(
smokd/
pickld/
1
Wheat
PDP
0.
0015
0.000015
B
1
1
Wheat
bran
11
Uncooked
12
Cooked:
NFS
13
Baked
1
Wheat
PDP
0.
0015
0.000015
B
1
1
Wheat
germ
12
Cooked:
NFS
13
Baked
14
Boiled
1
Wheat
PDP
0.
0015
0.000015
B
1
1
Wheat
germ
oil
13
Baked
1
Wheat
PDP
0.
0015
0.000015
B
1
1
Wheat
rough
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
1
Wheat
PDP
0.
0015
0.000015
B
1
1
Crop
Group
19:
Herbs
ans
Spices
Dill
(fresh)
13
Baked
14
Boiled
0.2
Tolerance
0.2
0.
004
B
1
3
2
Miscellaneous
Commodities
Asparagus
11
Uncooked
14
Boiled
15
Asparagus
FDA
0.
0032
RDF
#
74
NB
43
87
32
Canned:
Cooked
42
Frozen:
Cooked
15
Asparagus
FDA
0.
0032
RDF
#
74
PB
43
87
Bananas
Imports
only
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
TBD
Bananas
PDP
0.
01
RDF
#
75
NB
100
100
31
Canned:
NFS
32
Canned:
Cooked
TBD
Bananas
PDP
0.
01
RDF
#
75
PB
100
100
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
32
Bananas
dried
13
Baked
15
Fried
18
Dried
32
Canned:
Cooked
TBD
Bananas
PDP
0.
01
RDF
#
75
PB
100
100
Bananas
juice
11
Uncooked
31
Canned:
NFS
TBD
Bananas
PDP
0.
01
RDF
#
75
PB
100
100
Plantains
dried
TBD
Bananas
PDP
0.
01
RDF
#
75
PB
100
100
Plantains
green
15
Fried
TBD
Bananas
PDP
0.
01
RDF
#
75
NB
100
100
Plantains
ripe
11
Uncooked
14
Boiled
15
Fried
TBD
Bananas
PDP
0.
01
RDF
#
75
NB
100
100
Cranberries
11
Uncooked
12
Cooked:
NFS
13
Baked
18
Dried
31
Canned:
NFS
42
Frozen:
Cooked
3
Cranberries
FDA
0.001
RDF
#
76
PB
39
84
Cranberries
juice
11
Uncooked
12
Cooked:
NFS
31
Canned:
NFS
3
Cranberries
FDA
0.
001
RDF
#
76
PB
39
84
Cranberries
concentrate
31
Canned:
NFS
3
Cranberries
FDA
0.
001
RDF
#76
PB
39
84
Flax,
seed
Refined
0.
5
Flax
seed
FT
0.01
0.0001
B
1
1
Grapes
11
Uncooked
12
Cooked:
NFS
31
Canned:
NFS
41
Frozen:
NFS
10
Grapes
PDP
0.
016
RDF
#
77
PB
8
12
Grapes
juice
11
Uncooked
12
Cooked:
NFS
14
Boiled
31
Canned:
NFS
34
Canned:
Boiled
41
Frozen:
NFS
10
Grapes
juice
PDP
0.
010
RDF
#
78
PB
8
12
Grapes
juice
concentrate
12
Cooked:
NFS
13
Baked
14
Boiled
31
Canned:
NFS
41
Frozen:
NFS
10
Grapes
juice
PDP
0.
010
RDF
#
78
PB
8
12
Grapes
leaves
14
Boiled
10
Grapes
PDP
0.
016
RDF
#
77
PB
8
12
Grapes
raisins
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
18
Dried
42
Frozen:
Cooked
10
Grapes
PDP
0.
016
RDF
#
77
PB
8
12
Grapes
wine
and
sherry
99
Alcohol/
Fermented/
Distilled
10
Grapes
PDP
0.
016
RDF
#
77
PB
8
12
Okra
12
Cooked:
NFS
14
Boiled
15
Fried
4
Okra
FT
1.0
RDF
#
79
NB
32
94
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
33
32
Canned:
Cooked
42
Frozen:
Cooked
44
Frozen:
Boiled
4
Oka
FT
1.0
RDF
#79
PB
32
94
Olives
60
Canned:
Cured
10
Olive
FT
3.85
RDF
#
80
PB
1
3
2
Olive
oil
98
Refined
10
Olive
FT
3.85
0.077
B
1
3
2
Peanuts
butter
13
Baked
14
Boiled
0.05
Peanuts
FT
0.01
0.0006
B
3
6
Peanuts
hulled
12
Cooked:
NFS
13
Baked
14
Boiled
15
Fried
41
Frozen:
NFS
0.05
Peanuts
FT
0.01
0.0006
B
3
6
Peanuts
oil
98
Refined
0.05
Peanuts
FT
0.01
0.0006
B
3
6
Pineapples
dried
Imports
only
18
Dried
TBD
Pineapple
FDA
0.
053
RDF
#
82
RDF
#
95
RDF
#97
PB
1
3
2
Pineapples
juice
Imports
only
11
Uncooked
12
Cooked:
NFS
31
Canned:
NFS
42
Frozen:
Cooked
TBD
Pineapple
FDA
0.
053
RDF
#
82
RDF
#
95
RDF
#97
PB
1
3
2
Pineapples
juice
concentrate
Imports
only
12
Cooked:
NFS
31
Canned:
NFS
33
Canned:
Baked
41
Frozen:
NFS
TBD
Pineapple
FDA
0.
053
RDF
#
82
RDF
#
95
RDF
#97
PB
1
3
2
Pineapples
peeled
fruit
Imports
only
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
TBD
Pineapple
FDA
0.
053
RDF
#
81
RDF
#
95
RDF
#97
NB
1
3
2
Pineapples
peeled
fruit
Imports
only
31
Canned:
NFS
33
Canned:
Baked
41
Frozen:
NFS
TBD
Pineapple
FDA
0.
053
RDF
#
82
RDF
#
95
RDF
#97
PB
1
3
2
Pistachio
nuts
11
Uncooked
12
Cooked:
NFS
13
Baked
0.1
Pistachio
FT
0.03
RDF
#
83
PB
17
38
Prickly
pear
cactus,
pads
Cactus
pads
(nopal)
12
not
in
DEEM
Prickly
pear
cactus,
fruit
5
not
in
DEEM
Strawberries
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
31
Canned:
NFS
34
Canned:
Boiled
41
Frozen:
NFS
4
Strawberry
FDA
0.
0638
RDF
#
84
PB
16
24
Strawberries
juice
11
Uncooked
12
Cooked:
NFS
13
Baked
14
Boiled
31
Canned:
NFS
4
Strawberry
FDA
0.
0638
RDF
#
84
PB
16
24
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
Commodity
DEEM
Food
Form
Reassessed
Tolerance,
ppm
1
Data
Source
2
Anticipated
Residue
(ppm)
or
RDF
#
Blended
Classification
%
CT
Chronic
Acute
Avg
Max
Sunflower
oil
98
Refined
0.5
Sunflower
FT
0.
042
0.0004
B
1
1
Sunflower
seeds
11
Uncooked
13
Baked
0.5
Sunflower
FT
0.042
RDF
#
85
PB
1
1
Fish
Oysters
2
Tolerance
1.
See
Carbaryl
Product
and
Residue
Chemistry
Chapters
for
the
Reregistration
Eligibility
Decision.
DP
Barcode:
D238151.
2.
PDP
=
USDA
Pesticide
Data
Program;
FDA
=
FDA
Surveillance
Program
Data;
FT
=
field
trial
data;
P
=
processing.
3.
Reported
in
the
QUA
as
"Other
Crops"
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
35
Table
1b:
Summary
of
Market
Basket
Survey
Data
Commodity
DEEM
Food
Form
Market
Basket
Survey
Commodity
Used
RDF
#
%CT
Likely
Max
Citrus
Fruit
Citrus
citron
All
food
forms
Orange
RDF
#100
2
Grapefruit
All
food
forms
except
juice
RDF
#101
6
Kumquats
All
food
forms
RDF
#100
2
Lemons
All
food
forms
except
juice
RDF
#103
7
Limes
All
food
forms
except
juice
RDF
#100
2
Oranges
All
food
forms
except
juice
RDF
#45
5
Tangelos
All
food
forms
RDF
#100
2
Tangerine
All
food
forms
except
juice
RDF
#100
2
Pome
Fruit
Apples
All
food
forms
except
juice
and
apples,
dried
Apple
RDF
#
48
31
18
Dried
RDF
#
108
31
Pear
All
food
forms
RDF
#105
6
Quinces
All
food
forms
RDF
#107
2
Loquat
All
food
forms
RDF
#107
2
Crabapples
All
food
forms
RDF
#107
2
Stone
Fruits
Apricot
All
food
forms
Peach
RDF
#
98
2
Nectarines
All
food
forms
RDF
#104
24
Peaches
All
food
forms
RDF
#60
18
Plums
(damsons)
All
food
forms
RDF
#
106
9
Brassica
Vegetables
Broccoli
All
food
forms
Broccoli
RDF
#17
9
Cauliflower
All
food
forms
RDF
#
99
4
Leafy
Vegetables
Lettuce
head
11
Uncooked
Lettuce
RDF
#14
8
Lettuce
leaf
11
Uncooked
RDF
#102
2
Lettuce
(unspecified)
31
Canned:
NFS
RDF
#102
8
Fruiting
Vegetables
Tomato
All
food
forms
Tomato
RDF
#
33
27
Miscellaneous
Crops
Bananas
All
food
forms
Bananas
RDF
#
75
100
Plantains
All
food
forms
RDF
#
75
100
Grapes
All
food
forms
except
juice
Grapes
RDF
#
77
12
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
36
Table
2.
Residue
Distribution
Files
Garden
Beets
(roots)
Field
Trial
data
24
samples
RDF
#1
Garden
Beets
(roots)
27%
CT
Totalz=
65
Totalnz=
24
0.01
0.01
0.02
0.03
0.07
0.07
0.01
0.03
0.03
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.05
0.05
0.06
0.01
0.02
0.03
Sugarbeet
(roots)
Blended
Field
trial
data
Information
from
12/
2/
93
AR
memo
(S.
Hummel,
D193129,
12/
3/
93)
4%
CT
Average
Residue
=
0.01
ppm
Acute
AR
=
0.0004
Carrots
PDP
1994
1996
1888
samples/
0
detects
1/
2
LOD
=
0.0116
ppm
RDF
#2
Carrots
PDP
1994
96
6%
CT
Totalz=
94
Totalnz=
6
0.0116
0.0116
0.0116
0.0116
0.0116
0.0116
Chicory,
Horseradish,
Parsnip,
Salsify
(Carrots
PDP)
1994
1996
1888
samples/
0
detects
1/
2
LOD
=
0.0116
ppm
RDF
#3
Chic,
Horse,
Parsnip,
Salsify
(Carrots
PDP)
1994
96
2%
CT
Totalz=
98
Totalnz=
2
0.0116
0.0116
Chronic
AR
=
0.024
ppm
Chronic
AR
=
0.01
ppm
Chronic
AR
=
0.0116
ppm
Chronic
AR
=
0.0116
ppm
Potatoes
PDP
1994
1995
1401
samples/
0
detects
1/
2
LOD
=
0.0119
ppm
RDF
#4
Potatoes
PDP
1994
95
3%
CT
Totalz=
97
Totalnz=
3
0.0119
0.0119
0.0119
For
dried
potatoes
(blended)
acute
AR
=
0.00036
Radishes
(Garden
Beets
(roots)
Field
Trial
data
24
samples
RDF
#5
Radishes
(Garden
Beets
(roots))
2%
CT
Totalz=
1176
Totalnz=
24
0.01
0.01
0.02
0.03
0.07
0.07
0.01
0.03
0.03
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.05
0.05
0.06
0.01
0.02
0.03
Turnips
translate
to
rutabagas
Field
Trial
Data
27
samples
RDF
#6
Turnips
(roots)
2%
CT
Totalz=
1323
Totalnz=
27
0.01
0.01
0.02
0.07
0.11
0.13
0.01
0.02
0.03
0.72
0.93
1.01
0.01
0.01
0.02
0.02
0.02
0.04
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
Sweet
Potato
PDP
1559
samples/
3
detects
1996
1998
1/
2
LOD
=
0.011
ppm
RDF
#7
Sweet
potatoes
PDP
96
98
41
%
CT
Totalz
=
1512
Totalnz
=
3
44,
0.0059
0.67
0.01
0.29
Chronic
AR
=
0.0119
ppm
Chronic
AR
=
0.024
ppm
Chronic
AR
=0.121
ppm
Chronic
AR
=
0.0065
ppm
Garden
Beet
Tops
Field
Trial
Data
24
Samples
RDF
#8
Garden
beet
tops
27%
CT
Totalz=
63
Totalnz=
24
3.96
4.27
4.49
14.48
18.28
21.18
8.45
8.46
9.84
25.47
28.36
42.23
3.19
3.9
3.
91
2.41
2.71
4.65
1.63
1.77
1.9
8.64
9.2
10
Radish
Tops
(Garden
beet
tops)
Field
trial
data.
24
samples
RDF
#9
Radish
tops
(Garden
beet
tops
FT)
2%
CT
Totalz=
1176
Totalnz=
24
3.96
4.27
4.49
14.48
18.28
21.18
8.45
8.46
9.84
25.47
28.36
42.23
3.19
3.9
3.
91
2.
41
2.71
4.65
1.63
1.77
1.9
8.
64
9.
2
10
Turnip
tops
Field
Trial
data
33
samples
RDF
#10
Turnip
Tops
2%
CT
Totalz=
1617
Totalnz=
33
6.84
8.19
10.33
51.19
67.8
70.24
5.4
5.
41
5.88
6.91
9.04
9.73
49.12
49.24
50.27
1.07
1.09
1.49
10.97
11.35
14.5
7.69
9.25
11.71
1.56
1.83
1.84
5.28
5.76
6.83
2.07
2.13
3.68
Celery
PDP
1994
176
samples/
0
detects
1/
2
LOD
=
0.0152
ppm
RDF
#11
Celery
PDP
1994
6%
CT
Totalz=
94
Totalnz=
6
0.0152
0.0152
0.0152
0.0152
0.0152
0.0152
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
37
Chronic
AR
=
10.14
ppm
Chronic
AR
=
10.14
ppm
Chronic
AR
=
15.3
ppm
Chronic
AR
=
0.0152
ppm
Spinach
PDP
data
Translated
to
Dandelions
and
Parsley
1995
1997
1639
samples/
10
detects
1/
2
LOD
=
0.006
ppm
RDF
#
12
Spinach
PDP
2%
CT
Totalz=
1767
Totalnz=
10
25,
0.008
0.01
0.01
0.01
0.01
0.068
0.11
0.02
0.02
0.077
0.039
Canned
Spinach
PDP
1997
1998
863
samples/
no
detects
1/
2
LOD
=
0.006
ppm
RDF
#13
Canned
Spinach
2%
CT
Totalz=
98
Totalnz=
2
0.006
0.006
Head
Lettuce
PDP
1994
691
samples/
no
detects
1/
2
LOD
=
0.0169
ppm
RDF
#14
Lettuce
Head
8%
CT
=
Totalz=
92
Totalnz=
8
0.0169
0.0169
0.0169
0.0169
0.0169
0.0169
0.0169
0.0169
Leaf
Lettuce
FDA
translate
to
Endive
1992
1998
241
samples/
no
detects
1/
2
LOD
=
0.001
ppm
RDF
#15
Leaf
Lettuce
2%
CT
Totalz=
98
Totalnz=
2
0.001
0.001
Chronic
AR
=
0.0082
ppm
Chronic
AR
=
0.006
ppm
Chronic
AR
=
0.0169
ppm
Chronic
AR
=
0.001
ppm
Rhubarb/
Swiss
Chard
(Celery
PDP
1994)
176
samples/
0
detects
1/
2
LOD
=
0.0152
ppm
RDF
#16
Rhubarb
(Celery
PDP
1994)
2%
CT
Totalz=
98
Totalnz=
2
0.0152
0.0152
Broccoli
PDP
1994
679
samples/
1
detect
1/
2
LOD
=
0.0125
ppm
RDF
#
17
Broccoli
PDP
1994
9%
CT
Totalz=
618
Totalnz=
1
60,
0.013
0.007
Brussels
sprouts
(Cabbage
FDA
1992
1998)
246
samples/
0
detects
1/
2
LOD
=
0.001
ppm
RDF
#
18
Brussels
sprouts
(Cabbage
FDA
92
98)
67%
CT
Totalz
=
33
TotalFreq
=
1
67,
0.001
Cabbage
FDA
1992
1998
246
samples/
0
detects
1/
2
LOD
=
0.001
ppm
RDF
#
19
Cabbage
FDA
92
98
4%
CT
Totalz=
96
TotalFreq
=
1
4,
0.001
Chronic
AR
=
0.015
ppm
Chronic
AR
=
0.013
ppm
Chronic
AR
=
0.001
ppm
Chronic
AR
=
0.001
ppm
Cauliflower
(Broccoli
PDP
1994)
679
samples/
1
detect
1/
2
LOD
=
0.0125
ppm
RDF
#
20
Cauliflower
(Broccoli
PDP
1994)
4%
CT
Totalz=
652
Totalnz=
1
26,
0.013
0.007
Collards
Mustards
FT
data
24
samples
RDF
#
21
Collards
(Mustards
FT)
10%
CT
Totalz=
216
Totalnz=
24
0.65
0.72
0.99
1.8
2.31
2.68
3.47
3.63
3.8
2.57
2.79
2.99
0.3
0.
42
0.
95
1.83
3.38
4.71
4.93
7.76
8.29
0.99
1.61
3.23
Mustards,
Rape,
Kale
Mustards
FT
data
24
samples
RDF
#
22
Mustards
FT
2%
CT
Totalz=
1176
Totalnz=
24
0.65
0.72
0.99
1.8
2.31
2.68
3.47
3.63
3.8
2.57
2.79
2.99
0.3
0.
42
0.
95
1.83
3.38
4.71
4.93
7.76
8.29
0.99
1.61
3.23
Kohlrabi
(Cabbage
FDA
1992
1998)
246
samples/
0
detects
1/
2
LOD
=
0.001
ppm
RDF
#
23
Kohrabi
(Cabbage
FDA
92
98)
2%
CT
Totalz=
98
TotalFreq
=
1
2,
0.001
Chronic
AR
=
0.013
ppm
Chronic
AR
=
2.78
ppm
Chronic
AR
=
2.78
ppm
Chronic
AR
=
0.001
ppm
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
38
Dried
Beans
Blended
FT
data
3%
CT
1/
2
LOD
=
0.01
ppm
Residues
=
0.13
0.14
0.15
0.01
0.13
0.13
0.15
0.01
0.05
0.1
0.
16
0.01
0.01
0.01
0.01
0.07
0.01
0.01
0.01
0.06
0.05
Average
=
0.067
ppm
Acute
AR
=
0.002
Fresh
Succulent
Beans
PDP
1994
1995
1177
samples/
44
detects
21%
CT
4%
detects
1/
2
LOD
=
0.01
ppm
RDF
#
24
Fresh
Beans
21%
CT
Totalz=
930
Totalnz=
44
203,
0.0138
1.6
0.
067
0.45
0.9
0.096
0.064
0.11
0.23
0.37
0.011
0.26
0.086
0.046
0.15
0.06
0.06
0.011
0.04
0.007
0.15
0.007
0.1
0.
18
0.
93
0.15
0.12
0.26
0.082
0.2
0.57
0.25
0.025
0.037
0.31
0.29
0.29
0.13
0.15
1.4
0.
85
0.21
0.02
0.02
0.15
Processed
Succulent
Beans
PDP
1996
1998
1588
samples/
161
detects
16%
CT
10
%
detects
1/
2
LOD
=
0.006
ppm
RDF
#
25
Processed
Beans
16%
CT
Totalz=
1334
Totalnz=
161
242,
0.006
See
Appendix
L
for
residues
Lima
Beans
(Processed
Succulent
Beans
PDP
1996
1998)
1588
samples/
161
detects
16%
CT
10
%
detects
1/
2
LOD
=
0.006
ppm
RDF
#
26
Lima
Beans
30%
CT
Totalz=
1112
Totalnz=
161
315,
0.006
See
Appendix
L
for
residues
Chronic
AR
=
0.067
ppm
Chronic
AR
=
0.023
ppm
Chronic
AR
=
0.012
ppm
Chronic
AR
=
0.012
ppm
Peas
FDA
1992
1998
289
samples/
8
detects
1/
2
LOD
=
0.001
ppm
RDF
#27
Peas
Fresh
FDA
7%
CT
Totalz=
269
Totalnz=
8
12,
0.001
0.041
0.360
1.160
0.005
0.010
0.005
0.005
0.060
Processed
Peas
PDP
1994
1996
1458
samples/
19
detects
1/
2
LOD
=
0.011
ppm
RDF
#28
Processed
Peas
5%
CT
Totalz=
1385
Totalnz=
19
54,
0.011
0.13
0.43
0.086
0.12
0.06
0.01
0.028
0.042
0.06
0.14
0.067
0.0802
0.043
0.37
0.12
0.13
0.05
0.11
0.12
Dried
Peas
(Blended)
FT
data
9%
CT
1/
2
LOD
=
0.01
ppm
Residues
=
0.046
0.048
0.049
0.205
0.212
0.241
0.53
0.555
0.593
0.059
0.061
0.062
0.064
0.07
0.116
0.16
0.179
0.186
0.01
0.01
0.023
0.01
0.01
0.01
Average
=
0.146
Acute
AR
=
0.013
Soybean
(Blended)
PDP
data
749
samples/
0
detects
1%
CT
1/
2
LOD
=
0.0015
ppm
Acute
AR
=
0.000015
Chronic
AR
=
0.13
ppm
Chronic
AR
=0.013
ppm
Chronic
AR
=0.146
ppm
Chronic
AR
=
0.0015
ppm
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
39
Eggplant
FDA
1993
98
112
samples/
6
detects
1/
2
LOD
=
0.001
ppm
21%
CT
RDF
#
29
Eggplant
FDA
21%
CT
Totalz=
89
Totalnz=
6
17,
0.001
0.01
0.046
0.12
0.061
0.16
0.07
Hot
Pepper
FDA
1992
1998
347
samples/
66
detects
19%
detects
2%
CT
1/
2
LOD
=
0.001
ppm
RDF
#
30
Non
bell
peppers
19%
detects
Totalz=
281
Totalnz=
66
0.048
0.005
0.844
0.28
0.076
0.005
1
0.
9
0.46
0.03
0.016
0.35
1.6
0.
728
0.12
0.16
0.005
0.4
0.
04
0.
03
2.1
0.
31
1.
58
0.
17
0.22
0.9
2.
4
3.3
0.09
0.3
1.
7
0.1
0.5
1.7
1.
9
0.015
0.26
0.24
1.54
0.21
0.38
0.05
0.16
0.23
0.02
4
0.
43
0.
02
0.12
0.86
0.7
0.
8
0.05
0.25
0.15
0.3
0.2
0.1
0.
05
0.
9
0.2
0.
1
0.1
0.
2
0.02
0.06
Sweet
Pepper
FDA
1992
1998
430
samples/
28
detects
1/
2
LOD
=
0.001
ppm
RDF
#
31
Sweet
pepper
FDA
all
30%
CT
Totalz=
301
Totalnz=
28
101,
0.001
0.300
0.030
0.005
0.170
0.370
0.020
0.600
0.490
0.030
0.175
0.5
0.500
0.800
0.380
0.205
0.100
0.340
0.400
0.090
1.000
0.050
0.120
0.300
0.070
0.050
0.400
0.010
0.100
ProcessedTomatoes
PDP
1996
1998
1613
samples/
4
detects
(0.2%
detects)
1/
2
LOD
=
0.0043
ppm
RDF
#32
Tomatoes
PDP
27
%CT
0.2%
detects
Totalz=
1177
Totalnz=
4
432,
0.0043
0.008
0.004
0.017
0.007
Chronic
AR
=
0.005
ppm
Chronic
AR
=
0.108
ppm
Chronic
AR
=0.02
ppm
Chronic
AR
=
0.0044
ppm
Fresh
Tomatoes
PDP
1996
1998
1613
samples/
4
detects
(0.2%
detects)
1/
2
LOD
=
0.0043
ppm
RDF
#33
Tomatoes
PDP
11%
CT
0.2%
detects
Totalz=
1436
Totalnz=
4
173,
0.0043
0.008
0.004
0.017
0.007
Cucumber
FDA
1992
1998
420
samples/
13
detects
1/
2
LOD
=
0.001
ppm
RDF
#
34
Cucumber
FDA
32%
CT
3%
detects
Totalz=
286
Totalnz=
13
121,
0.001
0.005
0.005
0.005
0.230
0.182
0.121
0.005
0.100
0.070
0.190
0.018
0.034
0.010
Melons
(Cantaloupe
PDP
1998)
408
samples/
2
detects
(0.5%
detects)
1/
2
LOD
=
0.005
ppm
RDF
#
35
Cantaloupe
PDP
2%
CT
0.5%
detects
Totalz=
400
Totalnz=
2
6,
0.005
0.01
0.01
Cantaloupe
PDP
1998
408
samples/
2
detects
(0.5%
detects)
1/
2
LOD
=
0.005
ppm
RDF
#
36
Cantaloupe
PDP
9%
CT
0.5%
detects
Totalz=
364
Totalnz=
2
34,
0.005
0.01
0.01
Chronic
AR
=
0.0044
ppm
Chronic
AR
=
0.0033
ppm
Chronic
AR
=
0.0056
ppm
Chronic
AR
=
0.0056
ppm
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
40
Honey
dew
(Cantaloupe
PDP)
1998
408
samples/
2
detects
(0.5%
detects)
1/
2
LOD
=
0.005
ppm
RDF
#
37
Cantaloupe
PDP
44%
CT
0.5%
detects
Totalz=
228
Totalnz=
2
178,
0.005
0.01
0.01
Watermelon
FDA
1992
1998
330
samples/
4
detects
1/
2
LOD
=
0.001
ppm
RDF
#
38
Watermelon
FDA
15%
CT
1%
detects
Totalz=
281
Totalnz=
4
56,
0.001
0.06
0.1
0.04
0.094
Pumpkin
(Winter
Squash
PDP
1997
98)
970
samples/
1
detect
1/
2
LOD
=
0.005
ppm
RDF
#
39
Pumpkin
(Winter
Squash
PDP)
56
%
CT
0.1%
detects
Totalz=
426
Totalnz=
1
543,
0.006
0.013
Winter
Squash
PDP
1997
1998
970
samples/
1
detect
1/
2
LOD
=
0.005
ppm
RDF
#40
Winter
Squash
PDP
27
%
CT
0.1%
detects
Totalz=
708
Totalnz=
1
261,
0.006
0.013
Chronic
AR
=
0.0056
ppm
Chronic
AR
=
0.0019
ppm
Chronic
AR
=
0.006
ppm
Chronic
AR
=
0.006
ppm
Summer
Squash
FDA
1992
1998
406
samples/
10
detect
1/
2
LOD
0.001
ppm
27%
CT
RDF#
41
Summer
Squash
FDA
27%
CT
2%
detect
Totalz=
296
Totalnz=
10
100,
0.001
0.2
0.37
0.005
0.020
0.15
0.16
0.080
0.059
0.460
4.6
Citrus
citron,
Lime,
Tangelos,
Tangerine,
Grapefruit,
and
orange
(
partially
blended
food
forms)
(Orange
PDP
1994
1996)
1892
samples/
184
detects
1/
2
LOD
=
0.009
ppm
RDF
#42
Citrus
PDP
10%
detects
Totalz=
1656
Totalnz=
184
52,
0.009
see
Appendix
A
for
residue
values
Grapefruit
juice
(Orange
juice
PDP
data
1997
1998)
1392
samples/
30
detects
2%
detects
6%
CT
1/
2
LOD
=
0.006
ppm
RDF
#43
Grapefruit
juice
(Orange
juice
PDP)
2%
detects
6%
CT
Totalz=
1308
Totalnz=
30
54,
0.006
21,
0.01
7,
0.013
0.031
0.017
Lemon
juice
(Orange
juice
PDP
data
1997
1998)
1392
samples/
30
detects
2%
detects
7%
CT
1/
2
LOD
=
0.006
ppm
RDF
#44
Lemon
juice
(Orange
juice
PDP)
2%
detects
7%
CT
Totalz=
1295
Totalnz=
30
67,
0.006
21,
0.01
7,
0.013
0.031
0.017
Chronic
AR
=
0.016
ppm
Chronic
AR
=
0.013
ppm
Chronic
AR
=
0.006
ppm
Chronic
AR
=
0.006
ppm
Lime,
Tangelos,
Tangerine,
Grapefruit,
lemon,
and
orange
(not
blended
food
forms
)
(Orange
PDP
1994
1996)
1892
samples/
184
detects
Residues
decomp.
(n=
12)
Decomposited
residues
were
0.000043
to
1.68
ppm
1/
2
LOD
=
0.009
ppm
RDF
#45
Orange
PDP
decomposited
10%
detects
Totalz=
9000
Totalnz=
1000
see
Appendix
B
for
residue
values
Lime
juice,
tangerine
juice
(Orange
juice
PDP
data
1997
1998)
1392
samples/
30
detects
2%
detects
2%
CT
1/
2
LOD
=
0.006
ppm
RDF
#46
Lime
juice
(Orange
juice
PDP)
2%
detects
2%
CT
Totalz=
1362
Totalnz=
30
21,
0.01
7,
0.013
0.031
0.017
Orange
juice
PDP
data
1997
1998)
1392
samples/
30
detects
2%
detects
5%
CT
1/
2
LOD
=
0.006
ppm
RDF
#47
Orange
juice
PDP
2%
detects
5%
CT
Totalz=
1322
Totalnz=
30
40,
0.006
21,
0.01
7,
0.013
0.031
0.017
Apple
Non
blended
PDP
1994
1996
1909
samples/
285
detects
residues
decomposited
(n
=
15)
Decomposited
residues
range
from
0.00008
7.35
ppm
15%
detects
31%
CT
1/
2
LOD
=
0.013
ppm
RDF
#48
Apples
PDP
decomp
31%
CT
15%
detects
Totalz=
4600
Totalnz=
1000
1067,
0.013
(1/
2
LOD)
see
Appendix
C
for
residue
values
Chronic
AR
=
0.013
ppm
Chronic
AR
=
0.006
ppm
Chronic
AR
=0.006
ppm
Chronic
AR
=
0.03
ppm
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
41
Apples,
Dried
(Blended)
PDP
1994
96
1909
samples/
285
detects
31%
CT
1/
2
LOD
=
0.01
ppm
see
Appendix
D
for
residue
values
Average
=
0.03
Acute
AR
=
0.009
Apple
Partially
blended
PDP
data
1994
1996
1909
samples/
285
detects
15%
detects
31%
CT
1/
2
LOD
=
0.013
ppm
RDF
#49
Apples
PDP
31%
CT
15%
detects
Totalz=
1317
Totalnz=
285
see
Appendix
D
for
residue
values
Apple
Juice
PDP
1996
1998
1554
samples/
454
detects
29%
detects
31%
CT
1/
2
LOD
=
0.006
ppm
RDF
#
50
Apple
juice
PDP
31%
CT
15%
detects
Totalz=
1072
Totalnz=
454
28,
0.006
see
Appendix
E
for
residue
values
Pear
PDP
decomposition
1997
1998
1420
samples/
60
detects
4%
detects
6%
CT
1/
2
LOD
=
0.0065
ppm
n=
13
Decomp.
values
were
0.000026
to
14.33
RDF
#
51
Pear
PDP
Totalz=
23500
Totalnz=
1000
500,
0.0065
see
App.
F
for
residue
values
Chronic
AR
=
0.03
ppm
Chronic
AR
=
0.03
ppm
Chronic
AR
=
0.01
ppm
Chronic
AR
=
0.0098
ppm
Partially
blended
Pear
PDP
1997
1998
1420
samples/
60
detects
4%
detects
6%
CT
1/
2
LOD
=
0.0065
ppm
RDF
#
52
Pear
PDP
Totalz=
1335
Totalnz=
60
25,
0.0065
0.24
0.007
0.058
0.12
0.007
0.007
0.017
0.007
0.007
0.007
0.3
0.007
0.007
0.14
0.013
0.042
0.01
0.017
0.05
0.036
0.007
0.01
0.1
0.013
0.007
0.01
0.053
0.007
0.007
0.007
0.007
0.061
0.81
0.01
0.11
0.035
0.07
0.076
0.042
0.013
0.007
0.007
0.052
0.45
0.013
0.013
0.042
0.41
0.49
0.12
0.013
0.01
0.19
0.14
0.14
0.013
0.033
0.01
0.01
0.089
Quince
(Pear
PDP)
decomposition
1997
1998
1420
samples/
60
detects
4%
detects
2%
CT
1/
2
LOD
=
0.0065
ppm
n=
13
Decomp.
values
were
0.000026
to
14.33
RDF
#
53
Quince
PDP
Totalz=
73500
Totalnz=
1000
500,
0.0065
see
App.
F
for
residue
values
Crabapple
Apple
PDP
data
1994
1996
1909
samples/
285
detects
15%
detects
2%
CT
1/
2
LOD
=
0.013
ppm
RDF
#54
Crabapple
(Apple
PDP)
2%
CT
15%
detects
Totalz=
28910
Totalnz=
285
305,
0.013
see
Appendix
D
for
residue
values
Apricot
(Peach
PDP
1994
1996)
1088
samples/
168
detects
2%
CT
1/
2
LOD
=0.01
ppm
RDF
#55
Apricot
(Peach
PDP)
2
%CT
Totalz=
9604
Totalnz=
168
28,
0.01
See
Appendix
G
for
residue
values
Chronic
AR
=
0.0098
ppm
Chronic
AR
=
0.0098
ppm
Chronic
AR
=
0.033
ppm
Chronic
AR
=
0.07
ppm
Apricot
(Peach
PDP
1994
1996)
1088
samples/
168
detects
2%
CT
1/
2
LOD
=0.01
ppm
Residues
decomp.
ranged
from
0.000119
46.3
RDF
#56
Apricot
(Peach
PDP)
2
%CT
Totalz=
58800
Totalnz=
1000
200,
0.01
See
Appendix
H
for
residue
values
Sweet
Cherries
FDA
1992
98
281
samples/
89
detects
36%
CT
1/
2
LOD
=
0.001
ppm
RDF
#
57
Sweet
Cherries
36%
CT
Totalz=
180
Totalnz=
89
12,
0.001
see
Appendix
M
for
residue
values
Tart
Cherries
FDA
1992
98
281
samples/
89
detects
24%
CT
32%
detects
1/
2
LOD
=
0.001
ppm
RDF
#
58
Tart
Cherries
32%
detects
Totalz=
192
Totalnz=
89
see
Appendix
M
for
residue
values
Nectarines
(Peaches
PDP
1994
1996)
1088
samples/
168
detects
24%
CT
15%
detected
Residues
decomp.
ranged
from
0.000119
46.3
ppm
RDF
#
59
Peaches
PDP
decomp
24%
CT
15%
detected
Totalz=
5067
Totalnz=
1000
600,
0.001
see
Appendix
H
for
residue
values
Chronic
AR
=
0.07
ppm
Chronic
AR
=
0.127
ppm
Chronic
AR
=
0.127
ppm
Chronic
AR
=
0.07
ppm
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
42
Peaches
(not
blended)
PDP
Single
Serving
2000
1088
samples/
168
detects
18%
CT
15%
detected
Residues
decomp.
ranged
from
0.000119
46.3
RDF
#
60
Peaches
PDP
single
serving
18%
CT
15%
detected
Totalz=
438
Totalnz=
79
17,
0.003
see
Appendix
H
for
residue
values
Peaches
(partially
blended)
PDP
1994
1996
1088
samples/
168
detects
18%
CT
15%
detected
RDF
#
61
Peaches
PDP
18%
CT
15%
detected
Totalz=
892
Totalnz=
168
28,
0.001
see
Appendix
G
for
residue
values
Plums
FDA
FDA
1992
98
51
samples/
2
detects
4%
detects
9
%
CT
1/
2
LOD
=
0.001
ppm
RDF
#
62
Plums
FDA
9%
CT
Totalz=
46
Totalnz=
2
3,
0.001
0.002
0.002
Blackberries
(Raspberry
FDA
1992
98)
247
samples/
51
detects
21
%
Detects
44
%
CT
1/
2
LOD
=
0.001
ppm
RDF
#
63
Blackberry
(Raspberry
FDA)
21%
CT
Totalz=
138
Totalnz=
51
58,
0.001
3.79
1.52
1.18
0.019
0.04
0.436
2.78
0.298
3.43
0.032
0.028
0.005
0.016
1.13
0.021
0.19
0.02
0.005
0.005
0.005
0.005
0.005
0.005
0.005
0.005
0.03
0.13
0.005
0.045
0.16
0.13
0.08
0.005
0.034
1.07
0.007
0.063
0.16
0.88
0.005
0.026
0.005
0.35
0.06
0.83
0.005
0.06
3.2
0.23
0.005
0.12
Chronic
AR
=
0.07
ppm
Chronic
AR
=
0.07
ppm
Chronic
AR
=
0.07
ppm
Chronic
AR
=
0.09
ppm
Blueberry
FDA
1992
1998
212
samples/
23
detects
11
%
detects
45%
CT
1/
2
LOD
=
0.001
ppm
RDF
#64
Blueberry
FDA
45%
CT
11%
detects
Totalz=
117
Totalnz=
23
72,
0.001
0.342
0.245
1.06
0.146
0.112
0.206
0.234
0.005
0.19
4.38
0.119
0.005
0.005
0.52
0.23
2.05
0.08
9.7
0.005
0.02
0.054
0.15
0.012
Boysenberry,
Dewberry,
Loganberry,
Youngberry
(Raspberry
FDA
1992
98)
247
samples/
51
detects
21
%
Detects
2
%
CT
1/
2
LOD
=
0.001
ppm
RDF
#
65
Boysenberry
(Raspberry
FDA)
2%
CT
Totalz=
2499
Totalnz=
51
3.79
1.52
1.18
0.019
0.04
0.436
2.78
0.298
3.43
0.032
0.028
0.005
0.016
1.13
0.021
0.19
0.02
0.005
0.005
0.005
0.005
0.005
0.005
0.005
0.005
0.03
0.13
0.005
0.045
0.16
0.13
0.08
0.005
0.034
1.07
0.007
0.063
0.16
0.88
0.005
0.026
0.005
0.35
0.06
0.83
0.005
0.06
3.2
0.23
0.005
0.12
Currant,
Elderberries,
Gooseberries,
Huckleberries,
Olliaberry
(Blueberry
FDA)
1992
1998
153
samples/
15
detects
11
%
detects
2%
CT
1/
2
LOD
=
0.001
ppm
RDF
#66
Currant
(Blueberry
FDA)
2%
CT
Totalz=
4655
Totalnz=
23
72,
0.001
0.342
0.245
1.06
0.146
0.112
0.206
0.234
0.005
0.19
4.38
0.119
0.005
0.005
0.52
0.23
2.05
0.08
9.7
0.005
0.02
0.054
0.15
0.012
Raspberries
FDA
Raspberry
FDA
1992
98)
247
samples/
51
detects
21
%
Detects
10
%
CT
1/
2
LOD
=
0.001
ppm
RDF
#
67
Raspberry
FDA
10%
CT
21%
detected
Totalz=
196
Totalnz=
51
3.79
1.52
1.18
0.019
0.04
0.436
2.78
0.298
3.43
0.032
0.028
0.005
0.016
1.13
0.021
0.19
0.02
0.005
0.005
0.005
0.005
0.005
0.005
0.005
0.005
0.03
0.13
0.005
0.045
0.16
0.13
0.08
0.005
0.034
1.07
0.007
0.063
0.16
0.88
0.005
0.026
0.005
0.35
0.06
0.83
0.005
0.06
3.2
0.23
0.005
0.12
Chronic
AR
=
0.09
ppm
Chronic
AR
=
0.09
ppm
Chronic
AR
=
0.09
ppm
Chronic
AR
=
0.09
ppm
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
43
Almonds
FT
15
samples
RDF
#
68
Almonds
FT
4%
CT
Totalz=
360
Totalnz=
15
0.0614
0.0704
0.0786
0.0822
0.0826
0.0932
0.0304
0.0358
0.0380
0.0704
0.0800
0.0840
0.01
0.0300
0.0384
Chestnuts
(Almonds
FT)
15
samples
RDF
#
69
Chestnuts
(Almonds
FT)
2%
CT
Totalz=
735
Totalnz=
15
0.0614
0.0704
0.0786
0.0822
0.0826
0.0932
0.0304
0.0358
0.0380
0.0704
0.0800
0.0840
0.01
0.0300
0.0384
Filberts
(Pecan
FT)
18
samples
RDF
#
70
Filberts
(Pecan
FT)
12%
CT
Totalz=
132
Totalnz=
18
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.044
0.053
0.053
0.025
0.026
0.045
0.01
0.023
0.027
Pecan
FT
18
samples
RDF
#
71
Pecan
FT
24%
CT
Totalz=
57
Totalnz=
18
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.044
0.053
0.053
0.025
0.026
0.045
0.01
0.023
0.027
Chronic
AR
=
0.059
ppm
Chronic
AR
=
0.059
ppm
Chronic
AR
=
0.022
ppm
Chronic
AR
=
0.022
ppm
Walnut
FT
15
samples
2%
CT
RDF
#72
Walnut
FT
2%
CT
Totalz=
735
Totalnz=
15
0.044
0.064
0.153
0.037
0.043
0.052
0.507
0.811
0.999
0.266
0.389
0.65
0.01
0.01
0.01
Walnut
oil
FT
Blended
15
samples
2%
CT
Residues
=
0.044
0.064
0.153
0.037
0.043
0.052
0.507
0.811
0.999
0.266
0.389
0.65
0.01
0.01
0.01
Average
residue
=
0.27
Acute
AR
=
0.0054
Corn,
Fresh
PDP
1994
1996
1306
samples/
0
detects
1%
CT
1/
2
LOD
=
0.0085
RDF
#
73
Fresh
Corn
1%
CT
Totalz=
99
Totalnz=
1
0.0085
Chronic
AR
=
0.27
ppm
Chronic
AR
=
0.27
ppm
Chronic
AR
=
0.0085
ppm
Corn
grain
FT
Blended
0
detects
1/
2
LOD
=
0.01
1%
CT
Acute
AR
=
0.0001
Millet,
Sorghum,
Wheat
Blended
(Wheat
grain
PDP)
1563
samples/
6
detects
1%
CT
1557
@
1/
2
LOD
=
0.0015
0.011
0.004
0.01
0.013
0.005
0.005
Average
residue
=
0.0015
ppm
Acute
AR
=
0.000015
Rice
FT
Blended
24
samples
1%
CT
7.84
8.48
8.89
6.72
7.08
7.46
9.59
11.6
11.8
2.44
2.75
3.1
9.65
10
10.4
5.55
6.19
6.31
9.68
11.3
11.6
2.57
2.98
3.65
Average
Residue
=
7.4
ppm
Acute
AR
=
0.074
Asparagus
FDA
1992
98
381
samples/
6
detects
87%
CT
1/
2
LOD
=
0.001
ppm
RDF
#
74
Asparagus
FDA
87%
CT
Totalz=
50
Totalnz=
6
325,
0.001
0.087
0.504
0.005
0.180
0.069
0.005
Chronic
AR
=
0.01
ppm
Chronic
AR
=
0.0015
ppm
Chronic
AR
=
7.4
ppm
Chronic
AR
=
0.0032
ppm
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
44
Bananas
PDP
translate
to
plantains
1994
95
1126
samples/
0
detects
100
%
CT
1/
2
LOD
=
0.01
ppm
RDF
#
75
Bananas
PDP
100%
CT
Totalz=
0
Totalnz=
1
0.01
Cranberries
FDA
1992
98
111
samples/
3
detects
1/
2
LOD
=
0.001
ppm
RDF
#
76
Cranberries
FDA
84%
CT
Totalz=
18
Totalnz=
3
90,
0.001
0.002
0.002
0.002
Flax
seed
Blended
Field
Trial
10
samples
No
detects
<0.02
ppm
1%
CT
Average
Residues
=
1/
2
LOD
=
0.01
ppm
Acute
AR
=
0.0001
Grapes
PDP
1994
96
1884
samples/
65
detects
12%
CT
1/
2
LOD
=
0.01
ppm
RDF
#
77
Grapes
PDP
12%
CT
Totalz=
1658
Totalnz=
65
161,
0.01
0.94
0.01
0.011
0.011
0.011
0.011
0.013
0.017
0.017
0.017
0.017
0.02
0.02
0.02
0.02
0.025
0.025
0.025
0.025
0.036
0.042
0.042
0.042
0.042
0.047
0.053
0.057
0.061
0.063
0.063
0.067
0.068
0.068
0.071
0.079
0.086
0.088
0.11
0.11
0.12
0.12
0.12
0.13
0.13
0.14
0.15
0.18
0.19
0.19
0.22
0.23
0.23
0.24
0.25
0.29
0.29
0.34
0.38
0.42
0.43
0.48
0.5
0.52
0.54
0.62
Chronic
AR
=
0.01
ppm
Chronic
AR
=
0.001
ppm
Chronic
AR
=0.01
ppm
Chronic
AR
=
0.016
ppm
Grape
juice
PDP
1998
665
samples/
245
detects
37%
Detects
12
%
CT
RDF
#
78
Grape
juice
PDP
37%
detects
(12%
CT)
Totalz=
420
Totalnz=
245
See
Appendix
I
for
residues
Okra
Field
Trials
10
samples
RDF
#
79
Okra
FT
94%
CT
Totalz=
1
Totalnz=
10
2.5
2.99
0.152
0.155
0.399
0.546
0.105
0.32
1.17
1
.65
Olives
Field
Trials
12
samples
RDF
#
80
Olives
FT
2%
CT
Totalz=
588
Totalnz=
12
4.44
5.56
7.49
2.08
2.22
3.95
2.77
3.79
9.83
0.83
1.18
2.11
Olive
oil
(Olives)
Blended
Field
Trials
12
samples
2%
CT
4.44
5.56
7.49
2.08
2.22
3.95
2.77
3.79
9.83
0.83
1.18
2.11
Average
residue
=
3.85
Acute
AR
=
0.077
Chronic
AR
=0.01
ppm
Chronic
AR
=
1.0
ppm
Chronic
AR
=
3.85
ppm
Chronic
AR
=
3.85
ppm
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
45
Peanuts
Blended
Field
Trial
24
samples/
no
detects
LOD
=
<0.02
6%
CT
Average
Residue
=
1/
2
LOD
=
0.01
Acute
AR
=
0.0006
ppm
Pineapples
Mexico
(Not
blended
commodites)
Decomposited
Used
2.5%
i
n
Analysis
FDA
1992
98
Imports
only
116
Mexican
samples/
94
detects
81%
detects
1/
2
LOD
=
0.001
n
=
10
Residues
were
0.0001
42.7
RDF
#81
Pineapples
not
blended
81%
(detected)
Totalz=
235
Totalnz=
1000
see
appendix
K
for
residues
Pineapples
Mexico
(Partially
blended
commodities)
Used
2.5%
i
n
Analysis
FDA
1992
98
Imports
only
116
Mexican
samples/
94
detects
81%
detects
1/
2
LOD
=
0.001
RDF
#
82
Pineapples
Mexico
81%
CT
(detected)
Totalz=
22
Totalnz=
94
see
appendix
J
for
residues
Pistachios
Field
Trials
12
samples
RDF
#83
Pistachios
38%
CT
Totalz=
20
Totalnz=
12
0.026
0.026
0.03
0.01
0.01
0.01
0.073
0.089
0.099
0.01
0.01
0.01
Chronic
AR
=
0.01
ppm
Chronic
AR
=0.053
ppm
Chronic
AR
=
0.053
ppm
Chronic
AR
=0.03
ppm
Strawberry
FDA
1992
98
436
samples/
48
detects
1/
2
LOD
=
0.001
RDF
#84
Strawberry
FDA
24
%
CT
Totalz=
331
Totalnz=
48
57,
0.001
0.15
0.2
0.
02
0.
005
0.3
0.
5
0.4
0.
1
0.05
0.3
0.
2
0.005
0.002
0.6
0.
14
0.
005
0.6
3.12
5.3
0.
24
1.35
0.2
0.
24
0.
41
0.005
0.06
0.07
0.03
0.15
0.01
0.35
0.82
1.3
0.01
0.55
0.61
0.13
0.2
1.
1
0.1
3.6
1.7
0.
26
0.
11
0.
44
4
1
Sunflower
oil
Blended
Field
Trial
data
15
samples
1%
CT
Residues
0.01
0.029
0.036
0.01
0.01
0.01
0.01
0.01
0.01
0.065
0.079
0.090
0.047
0.077
0.129
Average
residue
=
0.04
Acute
AR
=
0.0004
Sunflower
seeds
Field
Trial
data
15
samples
1%
CT
RDF
#
85
Sunflower
FT
1%
CT
Totalz=
1485
Totalnz=
15
0.01
0.029
0.036
0.01
0.01
0.01
0.01
0.01
0.01
0.065
0.079
0.090
0.047
0.077
0.129
Milk
translate
to
ruminant
meat
and
fat
Feeding
study
%
CT
based
on
alfalfa,
feed
grains,
and
forages
%
CT
of
1%
RDF
#86
Milk
1%
CT
Totalz=
99
Totalnz=
1
0.0299
Chronic
AR
=
0.0638
ppm
Chronic
AR
=
0.04
ppm
Chronic
AR
=
0.04
ppm
Chronic
AR
=
0.0003
ppm
Ruminant
Liver
Feeding
study
%
CT
based
on
alfalfa,
feed
grains,
and
forages
%
CT
of
1%
RDF
#
87
Ruminant
Liver
1%
CT
Totalz=
99
Totalnz=
1
0.79
Ruminant
Kidney
Feeding
study
%
CT
based
on
alfalfa,
feed
grains,
and
forages
%
CT
of
1%
RDF
#
88
Ruminant
Kidney
1%
CT
Totalz=
99
Totalnz=
1
2.1
Swine
Meat
Feeding
study
%
CT
based
on
feed
grains,
and
forages
%
CT
of
1%
RDF
#
89
Swine
Meat
1%
CT
Totalz=
99
Totalnz=
1
0.036
Swine
Fat
Feeding
study
%
CT
based
on
feed
grains,
and
forages
%
CT
of
1%
RDF
#
90
Swine
Fat
1%
CT
Totalz=
99
Totalnz=
1
0.0192
Chronic
AR
=
0.0063
Chronic
AR
=
0.0179
Chronic
AR
=
0.000348
Chronic
AR
=
0.000096
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
46
Swine
Liver
Feeding
study
%
CT
based
on
feed
grains,
and
forages
%
CT
of
1%
RDF
#
91
Swine
Liver
1%
CT
Totalz=
99
Totalnz=
0.102
Swine
Kidney
Feeding
study
%
CT
based
on
feed
grains,
and
forages
%
CT
of
1%
RDF
#
92
Swine
Kidney
1%
CT
Totalz=
99
Totalnz=
0.168
Chronic
AR
=
0.000792
Chronic
AR
=
0.001428
Pineapple
other
countries
FDA
1992
98
Used
47.5%
of
analysis
No
detects
1/
2
LOD
=
0.001
ppm
RDF
#
95
Pineapples
other
countries
50%
CT
(detected)
Totalz=
26
Totalfreq=
1
25,
0.001
Plums
not
blended
(Peaches
PDP
1994
1996
)
1088
samples/
168
detects
18%
CT
15%
detected
Residues
decomp.
ranged
from
0.000119
46.3
RDF
#
96
Plums
(Peaches
PDP
decomp)
9%
CT
15%
detected
Totalz=
12133
Totalnz=
1000
200,
0.001
see
Appendix
H
for
residue
values
Pineapple
Domestic
No
exposure
Used
50%
of
analysis
RDF
#
97
Pineapples
domestic
0%
detected
Totalz=
26
Totalnz
=
0
Chronic
AR
=
0.053
ppm
Chronic
AR
=
0.07
ppm
Chronic
AR
=
0.053
ppm
Carbamate
Market
Basket
Study
RDFs
RDF
#
98
Number
of
samples
=
285
Apricots
(Peach
MBS)
2%
CT
20%
detected
Totalz=
2842
Totalnz=
58
0.0029
0.0013
0.0017
0.0018
0.0011
0.0029
0.0053
0.0019
0.0019
0.0026
1.1
0.
0018
0.56
0.0037
0.52
0.0014
1.2
0.
0025
0.0055
0.0067
1.1
0.13
0.23
0.010
0.0026
0.002
0.0013
0.021
0.0044
0.27
0.033
0.030
0.0096
0.18
0.022
0.0021
0.0061
0.0019
0.20
0.092
0.0019
0.0017
0.021
0.14
0.14
0.031
0.14
0.075
0.077
0.0012
0.061
0.040
0.0013
0.0099
0.26
0.0011
0.0020
0.047
RDF
#
99
Number
of
samples
=
395
Cauliflower
(Broccoli
MBS)
4%
CT
Totalz=
384
Totalfreq=
1
16,
0.0005
RDF
#
100
Number
of
samples
=
399
Other
Citrus
2%
CT
Totalz=
388
Totalnz=
11
0.0032
0.0017
0.015
0.0032
0.0017
0.0047
0.022
0.032
0.043
0.0052
0.013
RDF
#
101
Number
of
samples
=
399
Grapefruit
(OrangeMBS)
6%
CT
Totalz=
375
Totalnz=
11
13,
0.0005
0.0032
0.0017
0.015
0.0032
0.0017
0.0047
0.022
0.032
0.043
0.0052
0.013
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
47
RDF
#
102
Number
of
samples
=
399
Leaf
Lettuce
Market
Basket
Survey
2%
CT
Totalz=
392
Totalnz=
1
7,
0.0005
0.0014
RDF
#
103
Number
of
samples
=
399
Lemon
(Orange
MBS)
7%
CT
Totalz=
371
Totalnz=
11
17,
0.0005
0.0032
0.0017
0.015
0.0032
0.0017
0.0047
0.022
0.032
0.043
0.0052
0.013
RDF
#
104
Number
of
samples
=
285
Nectarines
(Peach
MBS)
24%
CT
20%
detected
Totalz=
217
Totalnz=
58
10,
0.0005
0.0029
0.0013
0.0017
0.0018
0.0011
0.0029
0.0053
0.0019
0.0019
0.0026
1.1
0.
0018
0.56
0.0037
0.52
0.0014
1.2
0.
0025
0.0055
0.0067
1.1
0.13
0.23
0.010
0.0026
0.002
0.0013
0.021
0.0044
0.27
0.033
0.030
0.0096
0.18
0.022
0.0021
0.0061
0.0019
0.20
0.092
0.0019
0.0017
0.021
0.14
0.14
0.031
0.14
0.075
0.077
0.0012
0.061
0.040
0.0013
0.0099
0.26
0.0011
0.0020
0.047
RDF
#
105
Number
of
samples
=
400
Pears
(Apple
MBS)
6%
CT
8%
detected
Totalz=
1943
Totalnz=
32
92,
0.0005
0.11
0.0011
0.11
0.21
0.017
0.0064
0.069
0.040
0.050
0.099
0.17
0.003
0.073
0.0011
0.021
0.005
0.0056
0.0059
0.054
0.016
0.0039
0.0012
0.14
0.0035
0.045
0.17
0.0085
0.0017
0.0024
0.035
0.068
0.093
RDF
#
106
Number
of
samples
=
285
Plum
(Peach
MBS)
4%
CT
20%
detected
Totalz=
1392
Totalnz=
58
0.0029
0.0013
0.0017
0.0018
0.0011
0.0029
0.0053
0.0019
0.0019
0.0026
1.1
0.
0018
0.56
0.0037
0.52
0.0014
1.2
0.
0025
0.0055
0.0067
1.1
0.13
0.23
0.010
0.0026
0.002
0.0013
0.021
0.0044
0.27
0.033
0.030
0.0096
0.18
0.022
0.0021
0.0061
0.0019
0.20
0.092
0.0019
0.0017
0.021
0.14
0.14
0.031
0.14
0.075
0.077
0.0012
0.061
0.040
0.0013
0.0099
0.26
0.0011
0.0020
0.047
RDF
#
107
Number
of
samples
=
400
Quince/
Crabapples
(Apple
MBS)
2%
CT
8%
detected
Totalz=
6076
Totalnz=
32
92,
0.0005
0.11
0.0011
0.11
0.21
0.017
0.0064
0.069
0.040
0.050
0.099
0.17
0.003
0.073
0.0011
0.021
0.005
0.0056
0.0059
0.054
0.016
0.0039
0.0012
0.14
0.0035
0.045
0.17
0.0085
0.0017
0.0024
0.035
0.068
0.093
RDF
#
108
Number
of
samples
=
400
Apples
dried
MBS
Totalnz=
32
Totalfreq=
1
368,
0.0005
0.11
0.0011
0.11
0.21
0.017
0.0064
0.069
0.040
0.050
0.099
0.17
0.003
0.073
0.0011
0.021
0.005
0.0056
0.0059
0.054
0.016
0.0039
0.0012
0.14
0.0035
0.045
0.17
0.0085
0.0017
0.0024
0.035
0.068
0.093
Replaces
RDF
#
14
Number
of
samples
=
399
Lettuce
Market
Basket
Survey
8%
CT
Totalz=
367
Totalnz=
1
31,
0.0005
0.0014
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
48
Replaces
RDF
#
17
Number
of
samples
=
395
Broccoli
Market
Basket
Survey
9%
CT
Totalz=
359
Totalfreq=
1
36,
0.0005
Replaces
RDF
#
33
Number
of
samples
=
399
Tomato
Market
Basket
Survey
27%
CT
Totalz=
291
Totalfreq=
1
108,
0.0005
Replaces
RDF
#
45
Number
of
samples
=
399
Orange
Market
Basket
Survey
5%
CT
Totalz=
379
Totalnz=
11
9,
0.0005
0.0032
0.0017
0.015
0.0032
0.0017
0.0047
0.022
0.032
0.043
0.0052
0.013
Replaces
RDF
#
48
Number
of
samples
=
400
Apples
Market
Basket
Survey
31%
CT
8%
detected
Totalz=
276
Totalnz=
32
92,
0.0005
0.11
0.0011
0.11
0.21
0.017
0.0064
0.069
0.040
0.050
0.099
0.17
0.003
0.073
0.0011
0.021
0.005
0.0056
0.0059
0.054
0.016
0.0039
0.0012
0.14
0.0035
0.045
0.17
0.0085
0.0017
0.0024
0.035
0.068
0.093
Replaces
RDF
#
60
Number
of
samples
=
285
Peach
Market
Basket
Survey
18%
CT
20%
detected
Totalz=
227
Totalnz=
58
0.0029
0.0013
0.0017
0.0018
0.0011
0.0029
0.0053
0.0019
0.0019
0.0026
1.1
0.
0018
0.56
0.0037
0.52
0.0014
1.2
0.
0025
0.0055
0.0067
1.1
0.13
0.23
0.010
0.0026
0.002
0.0013
0.021
0.0044
0.27
0.033
0.030
0.0096
0.18
0.022
0.0021
0.0061
0.0019
0.20
0.092
0.0019
0.0017
0.021
0.14
0.14
0.031
0.14
0.075
0.077
0.0012
0.061
0.040
0.0013
0.0099
0.26
0.0011
0.0020
0.047
Replaces
RDF
#
75
Number
of
samples
=
400
Bananas/
Plantains
100%
CT
Totalz=
0
Totalnz=
5
395,
0.0005
0.0019
0.0013
0.0011
0.0020
0.0016
Replaces
RDF
#
77
Number
of
samples
=
393
Grapes
Market
Basket
Survey
12%
CT
Totalz=
346
Totalnz=
31
16,
0.0005
0.0012
0.0026
0.020
0.21
0.030
0.0031
0.13
0.0027
0.032
0.015
0.28
0.073
0.0085
0.0011
0.012
0.062
0.010
0.19
0.0039
0.0012
0.0012
0.0013
0.0062
0.0032
0.014
0.18
0.78
0.36
0.022
0.0013
0.0011
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
49
Appendix
A
Orange
Residues
0.02
0.043
0.05
0.025
0.055
0.02
0.05
0.025
0.02
0.025
0.089
0.007
0.02
0.007
0.055
0.061
0.025
0.02
0.05
0.033
0.042
0.068
0.02
0.056
0.02
0.054
0.16
0.025
0.11
0.025
0.02
0.15
0.02
0.02
0.02
0.02
0.02
0.098
0.025
0.025
0.079
0.025
0.025
0.033
0.007
0.04
0.12
0.02
0.077
0.007
0.11
0.049
0.083
0.14
0.033
0.04
0.075
0.01
0.03
0.16
0.033
0.053
0.075
0.19
0.081
0.087
0.054
0.087
0.023
0.024
0.11
0.025
0.01
0.01
0.033
0.058
0.038
0.01
0.013
0.01
0.01
0.01
0.033
0.033
0.025
0.04
0.02
0.026
0.028
0.033
0.1
0.11
0.03
0.04
0.059
0.01
0.03
0.12
0.033
0.092
0.04
0.01
0.01
0.01
0.19
0.013
0.01
0.04
0.04
0.026
0.032
0.01
0.013
0.098
0.013
0.089
0.013
0.049
0.036
0.027
0.013
0.013
0.082
0.013
0.033
0.035
0.01
0.01
0.01
0.01
0.033
0.033
0.035
0.033
0.071
0.013
0.013
0.11
0.01
0.013
0.013
0.028
0.013
0.013
0.01
0.06
0.033
0.013
0.042
0.11
0.013
0.013
0.013
0.066
0.024
0.064
0.013
0.1
0.13
0.068
0.033
0.11
0.12
0.035
0.035
0.035
0.11
0.033
0.01
0.01
0.046
0.01
0.035
0.11
0.097
0.01
0.024
0.03
0.034
0.12
0.07
0.07
0.01
0.024
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
50
Appendix
B
Orange
residues
decomposited
0.000043
0.000153
0.000227
0.000249
0.000265
0.000276
0.000352
0.000366
0.000376
0.000408
0.000426
0.000450
0.000471
0.000485
0.000516
0.000545
0.000550
0.000571
0.000596
0.000615
0.000642
0.000663
0.000684
0.000699
0.000709
0.000726
0.000746
0.000779
0.000804
0.000807
0.000831
0.000838
0.000876
0.000886
0.000896
0.000897
0.000941
0.000954
0.000982
0.000992
0.001022
0.001027
0.001031
0.001038
0.001080
0.001099
0.001104
0.001107
0.001144
0.001161
0.001171
0.001175
0.001211
0.001231
0.001247
0.001268
0.001286
0.001303
0.001311
0.001314
0.001362
0.001368
0.001396
0.001396
0.001414
0.001418
0.001469
0.001470
0.001478
0.001498
0.001512
0.001531
0.001560
0.001561
0.001601
0.001607
0.001612
0.001629
0.001657
0.001666
0.001681
0.001714
0.001740
0.001746
0.001754
0.001762
0.001798
0.001811
0.001848
0.001851
0.001871
0.001884
0.001900
0.001913
0.001945
0.001951
0.001956
0.001988
0.002000
0.002002
0.002035
0.002060
0.002070
0.002079
0.002106
0.002113
0.002139
0.002152
0.002186
0.002190
0.002217
0.002229
0.002238
0.002245
0.002278
0.002305
0.002321
0.002344
0.002367
0.002379
0.002382
0.002395
0.002425
0.002448
0.002458
0.002477
0.002505
0.002512
0.002544
0.002546
0.002571
0.002575
0.002607
0.002612
0.002645
0.002661
0.002673
0.002675
0.002722
0.002724
0.002762
0.002763
0.002800
0.002807
0.002829
0.002846
0.002875
0.002893
0.002899
0.002901
0.002947
0.002958
0.002986
0.003012
0.003030
0.003045
0.003083
0.003086
0.003107
0.003123
0.003129
0.003167
0.003176
0.003179
0.003213
0.003215
0.003259
0.003265
0.003318
0.003322
0.003357
0.003359
0.003378
0.003385
0.003408
0.003439
0.003456
0.003457
0.003491
0.003498
0.003530
0.003547
0.003570
0.003588
0.003630
0.003638
0.003654
0.003680
0.003702
0.003727
0.003734
0.003744
0.003781
0.003802
0.003824
0.003834
0.003861
0.003864
0.003905
0.003934
0.003972
0.003979
0.004025
0.004030
0.004047
0.004058
0.004089
0.004115
0.004122
0.004126
0.004174
0.004179
0.004231
0.004231
0.004258
0.004279
0.004293
0.004305
0.004351
0.004357
0.004400
0.004414
0.004457
0.004465
0.004485
0.004496
0.004543
0.004551
0.004564
0.004569
0.004645
0.004647
0.004678
0.004699
0.004712
0.004744
0.004748
0.004767
0.004836
0.004838
0.004846
0.004870
0.004920
0.004927
0.004955
0.004973
0.004986
0.004992
0.005069
0.005073
0.005089
0.005090
0.005143
0.005147
0.005182
0.005226
0.005243
0.005264
0.005292
0.005316
0.005342
0.005350
0.005403
0.005405
0.005437
0.005470
0.005491
0.005518
0.005552
0.005556
0.005593
0.005619
0.005657
0.005671
0.005688
0.005694
0.005746
0.005757
0.005798
0.005804
0.005848
0.005877
0.005922
0.005938
0.005982
0.005989
0.006002
0.006005
0.006079
0.006092
0.006118
0.006140
0.006173
0.006183
0.006239
0.006267
0.006275
0.006304
0.006330
0.006363
0.006420
0.006425
0.006443
0.006445
0.006529
0.006529
0.006599
0.006601
0.006641
0.006653
0.006682
0.006710
0.006766
0.006774
0.006790
0.006811
0.006836
0.006840
0.006916
0.006951
0.006973
0.006989
0.007011
0.007042
0.007106
0.007128
0.007137
0.007153
0.007192
0.007224
0.007277
0.007293
0.007336
0.007356
0.007413
0.007417
0.007455
0.007462
0.007513
0.007554
0.007560
0.007616
0.007656
0.007667
0.007690
0.007698
0.007755
0.007794
0.007837
0.007865
0.007876
0.007900
0.007965
0.007992
0.008012
0.008064
0.008124
0.008131
0.008141
0.008155
0.008229
0.008240
0.008275
0.008300
0.008350
0.008377
0.008431
0.008455
0.008480
0.008510
0.008585
0.008607
0.008634
0.008674
0.008683
0.008718
0.008765
0.008816
0.008839
0.008857
0.008894
0.008902
0.008969
0.009025
0.009048
0.009088
0.009133
0.009161
0.009209
0.009237
0.009274
0.009281
0.009322
0.009380
0.009395
0.009441
0.009502
0.009536
0.009563
0.009591
0.009677
0.009684
0.009702
0.009725
0.009773
0.009796
0.009868
0.009914
0.009931
0.009959
0.010049
0.010059
0.010098
0.010157
0.010167
0.010201
0.010265
0.010316
0.010359
0.010363
0.010422
0.010436
0.010485
0.010544
0.010616
0.010618
0.010645
0.010698
0.010758
0.010787
0.010842
0.010871
0.010925
0.010929
0.011029
0.011040
0.011089
0.011112
0.011176
0.011222
0.011270
0.011279
0.011330
0.011370
0.011444
0.011493
0.011550
0.011555
0.011587
0.011634
0.011682
0.011758
0.011797
0.011842
0.011865
0.011872
0.011951
0.012023
0.012065
0.012074
0.012167
0.012185
0.012261
0.012272
0.012345
0.012379
0.012446
0.012480
0.012516
0.012595
0.012616
0.012666
0.012719
0.012760
0.012820
0.012860
0.012919
0.012947
0.013021
0.013075
0.013123
0.013183
0.013209
0.013268
0.013342
0.013382
0.013393
0.013430
0.013508
0.013509
0.013623
0.013656
0.013701
0.013728
0.013878
0.013899
0.013978
0.013992
0.014041
0.014051
0.014130
0.014180
0.014239
0.014319
0.014417
0.014441
0.014493
0.014507
0.014592
0.014638
0.014687
0.014732
0.014797
0.014852
0.014929
0.014953
0.015062
0.015073
0.015139
0.015157
0.015257
0.015330
0.015396
0.015400
0.015491
0.015563
0.015589
0.015650
0.015721
0.015737
0.015842
0.015918
0.015967
0.016059
0.016143
0.016147
0.016203
0.016228
0.016361
0.016396
0.016443
0.016488
0.016616
0.016642
0.016725
0.016749
0.016889
0.016948
0.017015
0.017041
0.017086
0.017104
0.017310
0.017332
0.017428
0.017460
0.017496
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
51
0.017556
0.017705
0.017726
0.017863
0.017866
0.017987
0.017991
0.018091
0.018114
0.018218
0.018228
0.018309
0.018341
0.018449
0.018525
0.018636
0.018725
0.018777
0.018830
0.018938
0.018973
0.019052
0.019056
0.019198
0.019289
0.019450
0.019461
0.019546
0.019561
0.019641
0.019763
0.019829
0.019897
0.019937
0.020018
0.020110
0.020148
0.020262
0.020399
0.020504
0.020542
0.020638
0.020702
0.020730
0.020762
0.020910
0.020939
0.021111
0.021215
0.021223
0.021307
0.021419
0.021437
0.021691
0.021723
0.021730
0.021852
0.021953
0.022014
0.022213
0.022237
0.022262
0.022424
0.022497
0.022522
0.022626
0.022781
0.022904
0.022943
0.023101
0.023156
0.023159
0.023254
0.023365
0.023439
0.023628
0.023699
0.023796
0.023869
0.023922
0.024071
0.024113
0.024237
0.024335
0.024493
0.024655
0.024676
0.024753
0.024842
0.024964
0.024994
0.025151
0.025181
0.025319
0.025415
0.025632
0.025691
0.025765
0.025819
0.026077
0.026119
0.026371
0.026378
0.026394
0.026527
0.026718
0.026797
0.026828
0.026896
0.027182
0.027267
0.027364
0.027411
0.027504
0.027606
0.027899
0.027959
0.028035
0.028140
0.028227
0.028239
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0.029099
0.029266
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0.029483
0.029540
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0.030160
0.030178
0.030263
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0.031922
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0.033018
0.033276
0.033495
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0.034478
0.034665
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0.035920
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0.036309
0.036516
0.036561
0.036855
0.037068
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0.037332
0.037615
0.037747
0.038035
0.038106
0.038159
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0.039178
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0.079174
0.079748
0.080194
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0.082453
0.082927
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0.084614
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0.088369
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0.096894
0.097932
0.099240
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0.101358
0.102634
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0.104062
0.104517
0.106154
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0.108714
0.109591
0.111546
0.111799
0.112381
0.112941
0.114951
0.115848
0.116366
0.117197
0.120985
0.120991
0.121752
0.122446
0.125247
0.126372
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0.128838
0.130456
0.131897
0.133229
0.134886
0.135468
0.136782
0.140523
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0.142335
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0.146687
0.147895
0.148973
0.150342
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0.179157
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0.184585
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0.188410
0.189242
0.195158
0.196066
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0.202731
0.211527
0.215130
0.219958
0.223187
0.225791
0.231400
0.235616
0.235634
0.246444
0.248895
0.257043
0.262337
0.268853
0.268969
0.284019
0.288194
0.303912
0.307660
0.322014
0.328990
0.339508
0.343924
0.375344
0.375349
0.420784
0.422542
0.445609
0.455397
0.479871
0.515625
0.553178
0.577879
0.727594
0.777848
0.938138
1.078748
1.183047
1.682955
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
52
Appendix
C.
Apples
Residues
Decomposited
1067,
0.013
0.000080
0.000151
0.000192
0.000236
0.000276
0.000280
0.000336
0.000380
0.000393
0.000438
0.000467
0.000496
0.000515
0.000523
0.000575
0.000597
0.000638
0.000650
0.000715
0.000727
0.000736
0.000765
0.000784
0.000821
0.000860
0.000871
0.000902
0.000924
0.000977
0.000992
0.000998
0.001014
0.001056
0.001086
0.001105
0.001140
0.001157
0.001160
0.001255
0.001255
0.001260
0.001276
0.001328
0.001360
0.001397
0.001409
0.001427
0.001460
0.001470
0.001502
0.001547
0.001563
0.001579
0.001582
0.001647
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0.001709
0.001730
0.001745
0.001762
0.001810
0.001813
0.001855
0.001856
0.001912
0.001913
0.001963
0.001981
0.002024
0.002048
0.002089
0.002106
0.002163
0.002169
0.002191
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0.002377
0.002380
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0.002575
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0.009469
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0.009840
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0.011291
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0.012377
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0.012703
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0.012842
0.012982
0.013000
0.013036
0.013115
0.013138
0.013209
0.013286
0.013292
0.013441
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0.013628
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0.013891
0.013990
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0.014577
0.014606
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0.017391
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0.017991
0.018180
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0.018590
0.018593
0.018872
0.018891
0.018992
0.019021
0.019115
0.019182
0.019265
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0.019465
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0.019651
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0.019860
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0.021554
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0.022353
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0.022609
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0.036857
0.036910
0.037177
0.037244
0.037480
0.037532
0.037717
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
53
0.037859
0.038028
0.038272
0.038431
0.038548
0.038971
0.039007
0.039121
0.039396
0.039455
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0.039871
0.040098
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Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
54
Appendix
D
Apple
Residues
305,
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1
1.2
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
55
Appendix
E
Apple
juice
residues
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Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
56
Appendix
F
Pear
Decomposition
Residues
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Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
57
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0.021190
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0.022705
0.022927
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0.023247
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0.028841
0.028915
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0.029330
0.029752
0.029859
0.029936
0.030172
0.030479
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0.030776
0.030854
0.031096
0.031135
0.031386
0.031509
0.031574
0.031787
0.032000
0.032106
0.032265
0.032474
0.032743
0.032892
0.032998
0.033174
0.033456
0.033597
0.033799
0.033859
0.034191
0.034302
0.034685
0.034863
0.034975
0.035135
0.035318
0.035475
0.035906
0.035933
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0.036834
0.036954
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0.037439
0.037667
0.037999
0.038145
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0.038642
0.038743
0.038758
0.039180
0.039533
0.039930
0.040011
0.040208
0.040488
0.040840
0.040889
0.041328
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0.041567
0.041647
0.042310
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0.042771
0.042986
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0.043922
0.044349
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0.045385
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0.046295
0.046762
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0.048815
0.048877
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0.050285
0.050412
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0.059668
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0.062601
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0.065114
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0.067092
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0.070863
0.071203
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0.075568
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0.080241
0.081229
0.081595
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0.083277
0.084056
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0.085699
0.085976
0.087475
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0.089190
0.090024
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0.091170
0.092987
0.093669
0.094206
0.095006
0.096872
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0.099170
0.099314
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0.104053
0.104335
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0.106487
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0.110185
0.110769
0.111133
0.113222
0.114098
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0.116052
0.117677
0.117870
0.119215
0.120431
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0.132692
0.133080
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0.139430
0.141720
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0.144600
0.146428
0.146697
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0.150355
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0.158216
0.161423
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0.164462
0.167179
0.169015
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0.175410
0.180147
0.180488
0.183248
0.183729
0.187348
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0.193960
0.194021
0.196644
0.201256
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0.206402
0.212607
0.212995
0.214853
0.215491
0.219796
0.220556
0.226726
0.233148
0.233802
0.233850
0.244874
0.248012
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0.253431
0.257551
0.260404
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0.274915
0.281823
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0.290413
0.295063
0.296701
0.297425
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0.317638
0.320699
0.329875
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0.335041
0.354246
0.360994
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0.385087
0.396786
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0.441123
0.442496
0.447060
0.465157
0.477866
0.485059
0.500223
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0.534092
0.547232
0.585947
0.604628
0.620898
0.654328
0.690641
0.694547
0.767175
0.771163
0.780800
0.824072
0.865476
0.938382
0.977047
0.993300
1.131298
1.141054
1.322287
1.396496
1.594982
1.708157
2.633765
2.742968
4.328884
14.332602
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
58
Appendix
G
peach
residue
data
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.013
0.013
0.013
0.013
0.017
0.02
0.02
0.023
0.024
0.025
0.025
0.029
0.029
0.03
0.031
0.033
0.033
0.033
0.033
0.033
0.033
0.033
0.033
0.033
0.034
0.04
0.04
0.041
0.042
0.053
0.055
0.056
0.058
0.059
0.06
0.06
0.06
0.06
0.061
0.066
0.069
0.069
0.072
0.072
0.075
0.082
0.084
0.11
0.11
0.11
0.12
0.12
0.13
0.13
0.13
0.13
0.13
0.14
0.14
0.14
0.14
0.15
0.15
0.16
0.17
0.17
0.17
0.18
0.18
0.18
0.19
0.19
0.2
0.2
0.2
0.21
0.21
0.22
0.24
0.24
0.25
0.28
0.29
0.29
0.29
0.3
0.3
0.3
0.31
0.31
0.33
0.35
0.37
0.37
0.38
0.42
0.42
0.43
0.45
0.45
0.45
0.45
0.46
0.47
0.47
0.47
0.48
0.49
0.5
0.57
0.6
0.6
0.61
0.62
0.63
0.65
0.68
0.7
0.71
0.71
0.71
0.72
0.74
0.79
0.81
0.83
0.86
0.87
0.88
0.91
0.91
0.92
0.93
0.94
0.96
0.97
0.99
1
1.1
1.1
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.3
1.3
1.3
1.4
1.7
1.8
2.3
4.8
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
59
Appendix
H
Peach
Single
serving
residues
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.011
0.022
0.025
0.026
0.03
0.031
0.031
0.041
0.042
0.046
0.049
0.051
0.052
0.054
0.057
0.06
0.065
0.071
0.073
0.083
0.087
0.094
0.1
0.11
0.11
0.12
0.13
0.14
0.14
0.15
0.15
0.15
0.15
0.15
0.16
0.16
0.18
0.2
0.21
0.24
0.25
0.29
0.34
0.37
0.41
0.49
0.5
0.51
0.54
0.56
0.58
0.59
0.76
0.94
0.94
1.2
1.5
2.7
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
60
Appendix
I
Grape
juice
residues
0.007
0.01
0.01
0.01
0.023
0.01
0.01
0.023
0.01
0.01
0.01
0.02
0.022
0.028
0.018
0.007
0.007
0.016
0.016
0.016
0.018
0.007
0.007
0.007
0.025
0.033
0.029
0.017
0.01
0.017
0.01
0.017
0.017
0.017
0.029
0.013
0.013
0.007
0.007
0.017
0.017
0.017
0.01
0.01
0.01
0.042
0.027
0.007
0.007
0.007
0.007
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.007
0.016
0.007
0.01
0.01
0.01
0.01
0.01
0.01
0.042
0.042
0.029
0.007
0.007
0.007
0.014
0.007
0.01
0.01
0.01
0.01
0.021
0.01
0.01
0.01
0.02
0.01
0.01
0.01
0.01
0.01
0.007
0.042
0.007
0.029
0.013
0.017
0.007
0.007
0.007
0.017
0.017
0.007
0.03
0.007
0.035
0.01
0.042
0.013
0.01
0.01
0.01
0.01
0.007
0.042
0.042
0.042
0.042
0.013
0.042
0.042
0.01
0.042
0.007
0.01
0.01
0.039
0.01
0.01
0.01
0.01
0.017
0.017
0.007
0.014
0.007
0.013
0.014
0.037
0.007
0.025
0.007
0.007
0.027
0.007
0.007
0.042
0.042
0.01
0.01
0.01
0.01
0.007
0.01
0.017
0.013
0.042
0.042
0.042
0.042
0.042
0.042
0.017
0.017
0.017
0.017
0.036
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.021
0.01
0.022
0.036
0.01
0.044
0.01
0.01
0.02
0.01
0.007
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.039
0.007
0.007
0.017
0.02
0.007
0.01
0.02
0.017
0.013
0.017
0.017
0.017
0.007
0.007
0.007
0.021
0.007
0.02
0.007
0.007
0.01
0.017
0.017
0.013
0.01
0.044
0.01
0.01
0.017
0.007
0.007
0.007
0.007
0.007
0.007
0.007
0.01
0.014
0.036
0.01
0.01
0.01
0.013
0.017
0.007
0.017
0.017
0.017
0.013
0.017
0.017
0.01
0.013
Appendix
J
Pineapple
Residues
0.005
0.005
0.005
0.005
0.005
0.01
0.02
0.02
0.08
0.08
0.09
0.1
0.12
0.14
0.14
0.15
0.16
0.16
0.2
0.21
0.22
0.22
0.26
0.277
0.29
0.3
0.3
0.3
0.37
0.42
0.43
0.45
0.45
0.48
0.5
0.5
0.5
0.5
0.52
0.6
0.6
0.6
0.62
0.627
0.64
0.66
0.66
0.69
0.7
0.7
0.73
0.75
0.76
0.79
0.8
0.91
1.01
1.04
1.06
1.07
1.08
1.08
1.12
1.15
1.2
1.24
1.3
1.3
1.39
1.43
1.5
1.5
1.51
1.6
1.6
1.66
1.72
1.73
1.8
1.94
2.2
2.47
2.6
2.75
3
3.02
3.3
3.42
4.37
4.4
4.47
4.95
5.2
5.22
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
61
Appendix
K
Pineapple
Decomposited
Numbers
0.000718
0.000904
0.002900
0.003992
0.004241
0.004793
0.005825
0.005828
0.006173
0.006653
0.006964
0.007583
0.008003
0.008311
0.008964
0.009030
0.009433
0.009514
0.010100
0.010172
0.010969
0.011046
0.011828
0.011889
0.012410
0.012558
0.013003
0.013396
0.013530
0.014095
0.014705
0.014761
0.014918
0.014927
0.015451
0.015780
0.016473
0.016539
0.016900
0.017143
0.017465
0.017658
0.018176
0.018630
0.019267
0.019327
0.019450
0.019993
0.020090
0.020623
0.020755
0.020774
0.021741
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0.022365
0.022412
0.022888
0.023104
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0.023843
0.023948
0.024210
0.024577
0.025145
0.025790
0.025838
0.026191
0.026445
0.026600
0.027045
0.027205
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0.027943
0.028399
0.028509
0.028733
0.029374
0.029390
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0.031133
0.031355
0.031493
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0.049453
0.049722
0.050648
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0.050973
0.052070
0.052273
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0.054522
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0.096894
0.098006
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0.169969
0.170529
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0.172334
0.172511
0.173842
0.174723
0.175051
0.176209
0.176495
0.177062
0.178607
0.179051
0.179837
0.180043
0.181105
0.181209
0.182417
0.183640
0.184962
0.185211
0.185843
0.186666
0.188181
0.188511
0.188757
0.190080
0.191511
0.191772
0.192558
0.192866
0.193993
0.194229
0.196442
0.196645
0.196920
0.198333
0.198700
0.199895
0.200224
0.200707
0.202350
0.203122
0.204141
0.204973
0.205489
0.205687
0.207347
0.207994
0.209542
0.209644
0.210533
0.210843
0.212477
0.213307
0.214026
0.215580
0.216184
0.216557
0.217800
0.218188
0.219633
0.220747
0.221154
0.221640
0.223903
0.224067
0.225424
0.226303
0.226732
0.228370
0.228534
0.229366
0.230369
0.230902
0.232654
0.234079
0.234730
0.235669
0.236099
0.236696
0.238257
0.239572
0.240440
0.241780
0.242473
0.243773
0.244849
0.244971
0.246452
0.247856
0.248543
0.249227
0.250296
0.250656
0.252140
0.253627
0.254950
0.254954
0.256461
0.256958
0.258290
0.258452
0.260758
0.261629
0.263017
0.263964
0.265867
0.266310
0.268245
0.268691
0.269026
0.270276
0.271623
0.272078
0.273369
0.273583
0.276637
0.277210
0.279194
0.279570
0.280170
0.281674
0.282474
0.284687
0.286531
0.286776
0.287374
0.288482
0.290124
0.291037
0.292565
0.293980
0.294975
0.295348
0.297263
0.297652
0.300817
0.301101
0.301567
0.303072
0.304310
0.305915
0.307202
0.308212
0.308995
0.309151
0.311996
0.313631
0.314373
0.315218
0.317073
0.317835
0.319003
0.319769
0.321688
0.323136
0.324331
0.325383
0.327617
0.327682
0.331635
0.332065
0.333542
0.334433
0.335579
0.335867
0.340140
0.340172
0.341520
0.342533
0.344072
0.345844
0.347539
0.347986
0.350294
0.350998
0.352585
0.353805
0.355453
0.357014
0.358724
0.358773
0.360903
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
62
0.361124
0.363787
0.364095
0.367969
0.368403
0.370158
0.371736
0.372530
0.374470
0.376488
0.378123
0.378768
0.380798
0.381983
0.383751
0.387275
0.387760
0.388249
0.388661
0.393416
0.393441
0.395311
0.396822
0.398445
0.399399
0.402223
0.402490
0.404933
0.405168
0.408471
0.411116
0.413747
0.414382
0.416421
0.417580
0.418531
0.419885
0.422516
0.422965
0.428129
0.428393
0.428683
0.430054
0.432418
0.433292
0.437375
0.437431
0.441615
0.442027
0.446280
0.446632
0.447884
0.448811
0.451327
0.451548
0.457231
0.457289
0.461332
0.461587
0.462831
0.464419
0.469012
0.469898
0.473803
0.473990
0.475937
0.476037
0.478848
0.481870
0.482272
0.486004
0.486828
0.487444
0.491531
0.492815
0.495931
0.498329
0.499129
0.501354
0.506098
0.506479
0.508190
0.510662
0.512668
0.513480
0.517681
0.519945
0.520945
0.521369
0.527984
0.528875
0.530006
0.530619
0.536849
0.538792
0.541101
0.541169
0.544316
0.546983
0.549240
0.550408
0.554769
0.555107
0.559827
0.560950
0.566796
0.567752
0.570936
0.571899
0.573328
0.574322
0.580862
0.582798
0.584566
0.588228
0.591821
0.593420
0.596863
0.597307
0.600453
0.601810
0.605851
0.606974
0.611799
0.613059
0.619969
0.620466
0.622735
0.623720
0.628878
0.631853
0.634406
0.635409
0.638075
0.642536
0.644705
0.646167
0.650440
0.653341
0.656763
0.657408
0.663254
0.666460
0.672296
0.672532
0.675261
0.677031
0.681322
0.683138
0.691583
0.691919
0.695152
0.695635
0.700351
0.702430
0.707562
0.710357
0.718160
0.719154
0.719715
0.723893
0.730890
0.730949
0.734032
0.738350
0.741023
0.741978
0.748290
0.750664
0.755970
0.756041
0.763608
0.768255
0.772535
0.776043
0.778055
0.782722
0.785676
0.788774
0.797664
0.797964
0.805356
0.806419
0.809958
0.810721
0.816879
0.819778
0.828085
0.830453
0.833670
0.834696
0.842047
0.846172
0.849968
0.852162
0.861878
0.863872
0.866703
0.874579
0.879443
0.879632
0.887051
0.891863
0.893710
0.899926
0.903513
0.908272
0.912342
0.915856
0.923117
0.926621
0.931957
0.932678
0.943922
0.945974
0.953793
0.955540
0.960579
0.970193
0.976637
0.979642
0.988480
0.990757
0.992980
0.998644
1.003321
1.009625
1.022624
1.022892
1.025879
1.029033
1.041915
1.046500
1.055282
1.058114
1.062761
1.064961
1.070699
1.072690
1.083888
1.093247
1.094587
1.105345
1.106683
1.115988
1.126098
1.127716
1.138713
1.141804
1.157459
1.157686
1.168917
1.170819
1.174904
1.179671
1.185744
1.188981
1.202694
1.211911
1.220818
1.227641
1.229894
1.232548
1.248643
1.251963
1.269976
1.270789
1.275805
1.286639
1.300162
1.303747
1.310995
1.317617
1.327844
1.329768
1.343275
1.344433
1.361054
1.372347
1.374447
1.385940
1.394743
1.402588
1.412313
1.420201
1.426382
1.428336
1.453538
1.463878
1.473549
1.473944
1.492403
1.502094
1.503803
1.512574
1.526334
1.532615
1.545653
1.564678
1.568884
1.585634
1.598885
1.602101
1.621827
1.622396
1.654688
1.655237
1.659049
1.677840
1.685873
1.687317
1.706891
1.724662
1.737939
1.738242
1.777588
1.777706
1.793182
1.808240
1.826915
1.834065
1.845563
1.859548
1.882921
1.888277
1.919239
1.923095
1.933142
1.933651
1.966528
1.969017
1.995951
1.999864
2.026351
2.037692
2.057432
2.066328
2.102841
2.107841
2.127051
2.154293
2.187142
2.197683
2.214135
2.214959
2.240506
2.272262
2.277981
2.310907
2.337914
2.354385
2.387846
2.405822
2.430035
2.431878
2.466880
2.487723
2.535230
2.547728
2.559498
2.588159
2.601811
2.640644
2.689642
2.698797
2.749880
2.754528
2.764741
2.794478
2.827427
2.871768
2.899381
2.903460
2.969468
3.002839
3.047839
3.059200
3.101256
3.111153
3.171463
3.173458
3.249091
3.268075
3.322117
3.326842
3.401713
3.404024
3.525221
3.562339
3.584484
3.650788
3.719527
3.764859
3.792282
3.882376
3.888121
3.908085
4.029110
4.045111
4.194307
4.197572
4.299340
4.347200
4.423226
4.455255
4.539802
4.667371
4.832164
4.834577
4.985608
5.019010
5.056245
5.234471
5.311164
5.419913
5.495525
5.659193
5.789586
5.849319
6.214068
6.216228
6.290479
6.341444
6.673090
6.812833
6.910124
6.989939
7.471261
7.543548
7.875357
8.204931
8.491655
8.591465
9.000151
9.209957
9.985838
10.354399
11.132104
11.447346
11.482575
11.749342
13.297935
14.257677
16.355846
17.270558
19.204660
20.976783
24.050741
27.526498
35.483131
35.782844
Attachment
1:
Anticipated
Residues
Summary
Table
and
Residue
Distribution
Files
63
Appendix
L
Processed
Succulent
Green
Bean
Residues
0.01
0.03
0.025
0.011
0.079
0.013
0.058
0.033
0.007
0.007
0.13
0.007
0.19
0.098
0.034
0.011
0.036
0.032
0.1
0.013
0.016
0.017
0.033
0.054
0.01
0.01
0.01
0.023
0.28
0.037
0.055
0.032
0.01
0.4
0.013
0.036
0.013
0.013
0.013
0.05
0.022
0.024
0.011
0.073
0.13
0.02
0.19
0.061
0.01
0.02
0.7
0.042
0.01
0.017
0.011
0.01
0.011
0.062
0.037
0.011
0.15
0.011
0.022
0.007
0.042
0.38
0.042
0.042
0.013
0.057
0.007
0.013
0.017
0.007
0.14
0.071
0.032
0.013
0.007
0.034
0.095
0.18
0.027
0.007
0.023
0.01
0.007
0.007
0.017
0.043
0.007
0.03
0.007
0.007
0.01
0.01
0.01
0.13
0.007
0.013
0.17
0.007
0.13
0.025
0.13
0.23
0.034
0.013
0.013
0.28
0.048
0.007
0.09
0.33
0.29
0.007
0.014
0.09
0.007
0.6
0.017
0.24
0.24
0.007
0.007
0.36
0.007
0.013
0.007
0.24
0.091
0.01
0.069
0.058
0.032
0.048
0.013
0.007
0.051
0.01
0.01
0.01
0.023
0.007
0.007
0.007
0.007
0.038
0.01
0.1
0.035
0.017
0.062
0.007
0.041
0.042
0.042
0.03
0.013
0.013
0.007
Appendix
M
Cherry
Residues
0.18
0.936
1.44
0.013
0.296
0.172
0.014
0.185
0.12
0.015
1.01
0.046
0.089
0.02
0.515
0.07
0.023
1.516
0.896
2.606
0.374
2.86
3.19
1.42
0.381
0.175
0.47
0.201
0.041
0.12
0.047
0.467
0.031
0.239
0.005
0.005
0.005
0.023
0.145
0.037
0.278
0.147
0.257
0.01
0.131
0.172
0.04
0.005
1.5
0.6
0.1
0.14
0.36
0.053
0.26
0.114
0.15
0.27
0.025
0.023
0.005
0.049
0.005
0.73
0.005
0.04
0.022
0.005
0.005
0.1
0.1
0.06
0.04
0.05
0.005
1.37
0.23
0.18
0.54
1.41
0.376
0.005
2.9
1.48
0.263
0.04
0.005
0.1
0.28
Attachment
2:
Chronic
and
Cancer
Dietary
Exposure
Analysis:
All
Commodities
64
Residue
File
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
Chronic
analysis
for
CARBARYL
1989
92
data
Residue
file:
C:\$
MyFiles\
Carbaryl\
Rdf
files\$$$
10chroniccarbarylfinal9.
RS7
Adjust.
#2
NOT
used
Analysis
Date
04
08
2002
Residue
file
dated:
04
08
2002/
14:
12:
04/
8
Reference
dose
(RfD)
=
0.01
mg/
kg
bw/
day
Food
Crop
RESIDUE
Adj.
Factors
Code
Grp
Food
Name
(ppm)
#1
#2
1
13A
Blackberries
0.092600
1.000
0.280
2
13A
Boysenberries
0.092600
1.000
0.010
3
13A
Dewberries
0.092600
1.000
0.010
4
13A
Loganberries
0.092600
1.000
0.010
5
13A
Raspberries
0.092600
1.000
0.040
6
13A
Youngberries
0.092600
1.000
0.010
7
13B
Blueberries
0.090000
1.000
0.220
8
O
Cranberries
0.001000
1.000
0.390
9
O
Cranberries
juice
0.001000
1.100
0.390
10
13B
Currants
0.090000
1.000
0.010
11
13B
Elderberries
0.090000
1.000
0.010
12
13B
Gooseberries
0.090000
1.000
0.010
13
O
Grapes
0.016000
1.000
0.080
14
O
Grapes
raisins
11
Uncooked
0.016000
2.170
0.080
12
Cooked:
NFS
0.016000
1.370
0.080
13
Baked
0.016000
1.370
0.080
14
Boiled
0.016000
1.370
0.080
18
Dried
0.016000
2.170
0.080
42
Frozen:
Cooked
0.016000
1.370
0.080
15
O
Grapes
juice
0.010000
1.200
0.080
16
13B
Huckleberries
0.090000
1.000
0.010
17
O
Strawberries
0.063800
1.000
0.160
20
10
Citrus
citron
0.013000
1.000
0.010
22
10
Grapefruit
peeled
fruit
11
Uncooked
0.013000
1.000
0.040
12
Cooked:
NFS
0.013000
1.000
0.040
14
Boiled
0.000000
1.000
1.000
31
Canned:
NFS
0.013000
1.000
0.040
23
10
Grapefruit
juice
0.006000
1.170
0.040
24
10
Kumquats
0.013000
1.000
0.010
26
10
Lemons
peeled
fruit
0.013000
1.000
0.030
27
10
Lemons
peel
0.013000
1.160
0.030
28
10
Lemons
juice
0.006000
1.110
0.030
30
10
Limes
peeled
fruit
0.013000
1.000
0.010
31
10
Limes
peel
0.013000
1.270
0.010
32
10
Limes
juice
0.006000
1.110
0.010
33
10
Oranges
juice
concentrate
0.006000
3.720
0.030
34
10
Oranges
peeled
fruit
11
Uncooked
0.013000
1.000
0.030
12
Cooked:
NFS
0.013000
1.000
0.030
31
Canned:
NFS
0.013000
1.000
0.030
35
10
Oranges
peel
0.013000
1.270
0.030
36
10
Oranges
juice
0.006000
1.000
0.030
37
10
Tangelos
0.013000
1.000
0.010
38
10
Tangerines
11
Uncooked
0.013000
1.000
0.010
31
Canned:
NFS
0.013000
1.000
0.010
41
Frozen:
NFS
0.013000
1.000
0.010
39
10
Tangerines
juice
0.006000
1.280
0.010
40
14
Almonds
0.059000
1.000
0.020
43
14
Chestnuts
0.059000
1.000
0.010
44
14
Filberts
(hazelnuts)
0.022000
1.000
0.040
47
14
Pecans
0.022000
1.000
0.200
48
14
Walnuts
0.270000
1.000
0.010
50
O
Pistachio
nuts
0.030000
1.000
0.170
52
11
Apples
11
Uncooked
0.030000
1.000
0.230
12
Cooked:
NFS
0.030000
1.000
0.230
13
Baked
0.030000
1.000
0.230
14
Boiled
0.030000
1.000
0.230
15
Fried
0.030000
1.000
0.230
18
Dried
0.030000
1.000
0.230
Attachment
2:
Chronic
and
Cancer
Dietary
Exposure
Analysis:
All
Commodities
65
31
Canned:
NFS
0.030000
1.000
0.230
32
Canned:
Cooked
0.030000
1.000
0.230
33
Canned:
Baked
0.030000
1.000
0.230
34
Canned:
Boiled
0.030000
1.000
0.230
42
Frozen:
Cooked
0.030000
1.000
0.230
53
11
Apples
dried
0.030000
2.580
0.230
54
11
Apples
juice/
cider
0.010000
1.000
0.230
55
11
Crabapples
0.030000
1.000
0.010
56
11
Pears
11
Uncooked
0.009800
1.000
0.030
12
Cooked:
NFS
0.009800
1.000
0.030
13
Baked
0.009800
1.000
0.030
14
Boiled
0.009800
1.000
0.030
31
Canned:
NFS
0.009800
1.000
0.030
57
11
Pears
dried
0.009800
2.580
0.030
58
11
Quinces
0.009800
1.000
0.010
59
12
Apricots
11
Uncooked
0.070000
1.000
0.010
12
Cooked:
NFS
0.070000
1.000
0.010
14
Boiled
0.070000
1.000
0.010
31
Canned:
NFS
0.070000
1.000
0.010
34
Canned:
Boiled
0.070000
1.000
0.010
60
12
Apricots
dried
0.070000
6.000
0.010
61
12
Cherries
11
Uncooked
0.127000
1.000
0.250
12
Cooked:
NFS
0.127000
1.000
0.120
13
Baked
0.127000
1.000
0.120
14
Boiled
0.127000
1.000
0.120
31
Canned:
NFS
0.127000
1.000
0.120
33
Canned:
Baked
0.127000
1.000
0.120
41
Frozen:
NFS
0.127000
1.000
0.120
62
12
Cherries
dried
0.127000
4.000
0.250
63
12
Cherries
juice
0.127000
1.500
0.120
64
12
Nectarines
0.070000
1.000
0.120
65
12
Peaches
11
Uncooked
0.070000
1.000
0.150
12
Cooked:
NFS
0.070000
1.000
0.150
13
Baked
0.070000
1.000
0.150
14
Boiled
0.070000
1.000
0.150
31
Canned:
NFS
0.070000
1.000
0.150
41
Frozen:
NFS
0.070000
1.000
0.150
66
12
Peaches
dried
0.070000
7.000
0.150
67
12
Plums
(damsons)
0.070000
0.260
0.050
68
12
Plums
prunes
(dried)
0.070000
0.150
0.050
69
12
Plums/
prune
juice
0.070000
1.400
0.050
72
O
Bananas
0.010000
1.000
1.000
73
O
Bananas
dried
0.010000
3.900
1.000
81
11
Loquats
0.009800
1.000
0.010
82
O
Olives
3.850000
1.000
0.010
89
O
Pineapples
peeled
fruit
11
Uncooked
0.053000
0.540
0.500
12
Cooked:
NFS
0.053000
0.540
0.500
13
Baked
0.053000
0.540
0.500
14
Boiled
0.053000
0.540
0.500
31
Canned:
NFS
0.053000
0.540
0.500
33
Canned:
Baked
0.053000
0.540
0.500
41
Frozen:
NFS
0.053000
0.540
0.500
90
O
Pineapples
dried
0.053000
5.000
0.500
91
O
Pineapples
juice
0.053000
0.540
0.500
94
O
Plantains
ripe
0.010000
1.000
1.000
123
19A
Dill
0.200000
1.000
0.010
126
1AB
Horseradish
0.011600
1.000
0.010
139
8
Paprika
0.108000
1.000
0.010
141
9A
Melons
cantaloupes
juice
0.005600
1.000
0.070
142
9A
Melons
cantaloupes
pulp
0.005600
1.000
0.070
143
9A
Casabas
0.005600
1.000
0.010
144
9A
Crenshaws
0.005600
1.000
0.010
145
9A
Melons
honeydew
0.005600
1.000
0.190
146
9A
Melons
persian
0.005600
1.000
0.010
147
9A
Watermelon
0.001900
1.000
0.130
148
9B
Cucumbers
0.003300
1.000
0.140
149
9B
Pumpkin
0.006270
1.000
0.310
150
9B
Squash
summer
0.016000
1.000
0.110
151
9B
Squash
winter
0.006000
1.000
0.110
152
9B
Bitter
melon
0.005600
1.000
0.010
154
8
Eggplant
0.005000
1.000
0.090
155
8
Peppers
sweet(
garden)
0.020000
1.000
0.130
156
8
Peppers
chilli
incl
jalapeno
0.108000
1.000
0.010
Attachment
2:
Chronic
and
Cancer
Dietary
Exposure
Analysis:
All
Commodities
66
157
8
Peppers
other
0.108000
1.000
0.010
158
8
Pimientos
0.108000
1.000
0.010
159
8
Tomatoes
whole
11
Uncooked
0.004000
1.000
0.050
12
Cooked:
NFS
0.004000
1.000
0.050
13
Baked
0.004000
1.000
0.050
14
Boiled
0.004000
1.000
0.050
15
Fried
0.004000
1.000
0.050
31
Canned:
NFS
0.004000
1.000
0.150
32
Canned:
Cooked
0.004000
1.000
0.150
33
Canned:
Baked
0.004000
1.000
0.150
34
Canned:
Boiled
0.004000
1.000
0.150
42
Frozen:
Cooked
0.004000
1.000
0.150
160
8
Tomatoes
juice
0.004000
0.520
0.150
161
8
Tomatoes
puree
0.004000
0.650
0.150
162
8
Tomatoes
paste
0.004000
0.650
0.150
163
8
Tomatoes
catsup
0.004000
0.650
0.150
165
2
Beets
garden
tops(
greens)
10.140000
1.000
0.170
166
4B
Celery
0.015200
1.000
0.030
168
5A
Broccoli
0.013000
1.000
0.040
169
5A
Brussels
sprouts
0.001000
1.000
0.330
170
5A
Cabbage
green
and
red
11
Uncooked
0.001000
0.250
0.020
12
Cooked:
NFS
0.001000
0.025
0.020
13
Baked
0.001000
0.025
0.020
14
Boiled
0.001000
0.025
0.020
15
Fried
0.001000
0.025
0.020
31
Canned:
NFS
0.001000
0.250
0.020
32
Canned:
Cooked
0.001000
0.025
0.020
51
Cured:
NFS
(smoked/
pickled/
saltd)
0.001000
0.025
0.020
171
5A
Cauliflower
0.013000
1.000
0.020
172
5B
Collards
2.780000
1.000
0.040
174
5B
Kale
2.780000
1.000
0.010
175
5A
Kohlrabi
0.001000
1.000
0.010
176
4A
Lettuce
leafy
varieties
0.001000
1.000
0.010
177
4A
Dandelion
greens
0.008200
1.000
0.010
178
4A
Endive
curley
and
escarole
0.001000
1.000
0.010
182
4A
Lettuce
unspecified
0.016900
1.000
0.030
183
5B
Mustard
greens
2.780000
1.000
0.010
184
4A
Parsley
0.008200
1.000
0.010
185
4B
Rhubarb
0.015200
1.000
0.010
186
4A
Spinach
11
Uncooked
0.008200
1.000
0.010
12
Cooked:
NFS
0.008200
1.000
0.010
13
Baked
0.008200
1.000
0.010
14
Boiled
0.008200
1.000
0.010
31
Canned:
NFS
0.006000
1.000
0.010
32
Canned:
Cooked
0.006000
1.000
0.010
34
Canned:
Boiled
0.006000
1.000
0.010
42
Frozen:
Cooked
0.008200
1.000
0.010
44
Frozen:
Boiled
0.008200
1.000
0.010
187
4B
Swiss
chard
0.015200
1.000
0.010
188
2
Turnips
tops
15.300000
1.000
0.010
192
4A
Lettuce
head
varieties
0.016900
1.000
0.030
195
O
Grapes
leaves
0.016000
1.000
0.080
197
1AB
Beets
garden
roots
0.024000
1.000
0.170
198
1AB
Carrots
0.011600
1.000
0.040
207
1C
Potatoes/
white
whole
11
Uncooked
0.011900
1.000
0.020
12
Cooked:
NFS
0.011900
1.000
0.020
13
Baked
0.011900
1.200
0.020
14
Boiled
0.011900
2.500
0.020
15
Fried
0.011900
0.040
0.020
31
Canned:
NFS
0.011900
1.000
0.020
208
1C
Potatoes/
white
unspecified
0.011900
1.000
0.020
209
1C
Potatoes/
white
peeled
11
Uncooked
0.011900
1.000
0.020
12
Cooked:
NFS
0.011900
1.000
0.020
13
Baked
0.011900
1.200
0.020
14
Boiled
0.011900
2.500
0.020
15
Fried
0.011900
0.040
0.020
31
Canned:
NFS
0.011900
1.000
0.020
32
Canned:
Cooked
0.011900
1.000
0.020
34
Canned:
Boiled
0.011900
2.500
0.020
42
Frozen:
Cooked
0.011900
1.000
0.020
43
Frozen:
Baked
0.011900
1.200
0.020
45
Frozen:
Fried
0.011900
0.040
0.020
Attachment
2:
Chronic
and
Cancer
Dietary
Exposure
Analysis:
All
Commodities
67
210
1C
Potatoes/
white
dry
0.011900
0.400
0.020
211
1C
Potatoes/
white
peel
only
13
Baked
0.011900
1.200
0.020
15
Fried
0.011900
0.040
0.020
212
1AB
Radishes
roots
0.024000
1.000
0.010
213
2
Radishes
tops
10.140000
1.000
0.010
214
1AB
Rutabagas
roots
0.121000
1.000
0.010
215
2
Rutabagas
tops
15.300000
1.000
0.010
216
1AB
Salsify(
oyster
plant)
0.011600
1.000
0.010
218
1CD
Sweet
potatoes
(incl
yams)
0.006500
1.000
0.180
219
1AB
Turnips
roots
0.121000
1.000
0.010
220
1AB
Parsnips
0.011600
1.000
0.010
227
6C
Beans
dry
great
northern
0.067000
1.000
0.010
228
6C
Beans
dry
kidney
0.067000
1.000
0.010
229
6C
Beans
dry
lima
0.067000
1.000
0.010
230
6C
Beans
dry
navy
(pea)
0.067000
1.000
0.010
231
6C
Beans
dry
other
0.067000
1.000
0.010
232
6C
Beans
dry
pinto
0.067000
1.000
0.010
233
6B
Beans
succulent
lima
0.011780
1.000
0.130
234
6A
Beans
succulent
green
11
Uncooked
0.023200
1.000
0.140
12
Cooked:
NFS
0.023200
1.000
0.140
14
Boiled
0.023200
1.000
0.140
31
Canned:
NFS
0.011780
1.000
0.100
32
Canned:
Cooked
0.011780
1.000
0.100
34
Canned:
Boiled
0.011780
1.000
0.100
42
Frozen:
Cooked
0.011780
1.000
0.100
44
Frozen:
Boiled
0.011780
1.000
0.100
51
Cured:
NFS
(smoked/
pickled/
saltd)
0.011780
1.000
0.100
235
6A
Beans
succulent
other
0.011780
1.000
0.100
236
6A
Beans
succulent
yellow/
wax
14
Boiled
0.023200
1.000
0.140
32
Canned:
Cooked
0.011780
1.000
0.100
42
Frozen:
Cooked
0.011780
1.000
0.100
237
15
Corn/
pop
0.010000
1.000
0.010
238
15
Corn/
sweet
0.008500
1.000
0.010
240
6C
Peas
(garden)
dry
12
Cooked:
NFS
0.146000
0.045
0.030
14
Boiled
0.146000
0.045
0.030
31
Canned:
NFS
0.146000
0.300
0.030
32
Canned:
Cooked
0.146000
0.045
0.030
34
Canned:
Boiled
0.146000
0.045
0.030
241
6AB
Peas
(garden)
green
11
Uncooked
0.130000
0.300
0.020
12
Cooked:
NFS
0.130000
0.300
0.020
13
Baked
0.130000
0.300
0.020
14
Boiled
0.130000
0.300
0.020
15
Fried
0.130000
0.300
0.020
31
Canned:
NFS
0.012700
1.000
0.010
32
Canned:
Cooked
0.012700
1.000
0.010
34
Canned:
Boiled
0.012700
1.000
0.010
42
Frozen:
Cooked
0.012700
1.000
0.010
44
Frozen:
Boiled
0.012700
1.000
0.010
45
Frozen:
Fried
0.012700
1.000
0.010
243
6C
Lentils
0.067000
1.000
0.010
244
6C
Mung
beans
(sprouts)
0.067000
1.000
0.010
245
O
Okra
12
Cooked:
NFS
1.000000
0.180
0.320
14
Boiled
1.000000
0.050
0.320
15
Fried
1.000000
0.180
0.320
32
Canned:
Cooked
1.000000
0.180
0.320
42
Frozen:
Cooked
1.000000
0.180
0.320
44
Frozen:
Boiled
1.000000
0.050
0.320
249
6C
Beans
dry
broadbeans
0.067000
1.000
0.010
250
6B
Beans
succulent
broadbeans
0.023200
1.000
0.140
251
6C
Beans
dry
pigeon
beans
0.067000
1.000
0.010
253
6
Beans
unspecified
0.023200
1.000
0.140
255
6A
Soybeans
sprouted
seeds
0.001500
0.330
0.010
256
Beans
dry
hyacinth
0.067000
1.000
0.010
257
Beans
succulent
hyacinth
0.023200
1.000
0.140
258
6C
Beans
dry
blackeye
peas/
cowpea
0.067000
1.000
0.010
259
6C
Beans
dry
garbanzo/
chick
pea
0.067000
1.000
0.010
260
O
Asparagus
0.003200
1.000
0.430
266
15
Corn
grain
endosperm
0.008500
1.000
0.010
267
15
Corn
grain
bran
0.008500
1.000
0.010
268
15
Corn
grain/
sugar/
hfcs
0.008500
1.500
0.010
270
15
Rice
rough
(brown)
7.400000
1.000
0.010
Attachment
2:
Chronic
and
Cancer
Dietary
Exposure
Analysis:
All
Commodities
68
271
15
Rice
milled
(white)
7.400000
0.030
0.010
275
15
Sorghum
(including
milo)
0.001500
1.000
0.010
276
15
Wheat
rough
0.001500
1.000
0.010
277
15
Wheat
germ
0.001500
0.650
0.010
278
15
Wheat
bran
0.001500
1.000
0.010
279
15
Wheat
flour
0.001500
0.100
0.010
280
15
Millet
0.001500
1.000
0.010
282
1A
Sugar
beet
0.010000
0.040
0.020
287
6C
Guar
beans
0.023200
1.000
0.140
289
15
Corn
grain
oil
0.008500
0.250
0.010
292
O
Flax
seed
0.010000
1.000
0.010
293
O
Peanuts
oil
0.010000
0.290
0.030
297
6A
Soybeans
oil
0.001500
0.005
0.010
298
O
Sunflower
oil
0.042000
0.030
0.010
300
O
Olive
oil
3.850000
0.810
0.010
303
6A
Soybean
other
0.001500
1.000
0.010
304
6A
Soybeans
mature
seeds
dry
0.001500
1.000
0.010
305
6A
Soybeans
flour
(full
fat)
0.001500
1.000
0.010
306
6A
Soybeans
flour
(low
fat)
0.001500
1.000
0.010
307
6A
Soybeans
flour
(defatted)
0.001500
1.000
0.010
315
O
Grapes
wine
and
sherry
0.016000
1.000
0.080
318
D
Milk
nonfat
solids
0.000300
1.000
0.230
319
D
Milk
fat
solids
0.000300
1.000
0.230
320
D
Milk
sugar
(lactose)
0.000300
1.000
0.230
321
M
Beef
meat
byproducts
0.017900
1.000
0.230
322
M
Beef
other
organ
meats
0.017900
1.000
0.230
323
M
Beef
dried
0.000300
1.920
0.230
324
M
Beef
fat
w/
o
bones
0.000300
1.000
0.230
325
M
Beef
kidney
0.017900
1.000
0.230
326
M
Beef
liver
0.006300
1.000
0.230
327
M
Beef
lean
(fat/
free)
w/
o
bones
0.000300
1.000
0.230
328
M
Goat
meat
byproducts
0.017900
1.000
0.230
329
M
Goat
other
organ
meats
0.017900
1.000
0.230
330
M
Goat
fat
w/
o
bone
0.000300
1.000
0.230
331
M
Goat
kidney
0.017900
1.000
0.230
332
M
Goat
liver
0.006300
1.000
0.230
333
M
Goat
lean
(fat/
free)
w/
o
bone
0.000300
1.000
0.230
336
M
Sheep
meat
byproducts
0.017900
1.000
0.230
337
M
Sheep
other
organ
meats
0.017900
1.000
0.230
338
M
Sheep
fat
w/
o
bone
0.000300
1.000
0.230
339
M
Sheep
kidney
0.017900
1.000
0.230
340
M
Sheep
liver
0.006300
1.000
0.230
341
M
Sheep
lean
(fat
free)
w/
o
bone
0.000300
1.000
0.230
342
M
Pork
meat
byproducts
0.001428
1.000
0.230
343
M
Pork
other
organ
meats
0.001428
1.000
0.230
344
M
Pork
fat
w/
o
bone
0.000094
1.000
0.230
345
M
Pork
kidney
0.001428
1.000
0.230
346
M
Pork
liver
0.000792
1.000
0.230
347
M
Pork
lean
(fat
free)
w/
o
bone
0.000348
1.000
0.230
349
F
Fish
shellfish
0.250000
1.000
1.000
377
11
Apples
juice
concentrate
0.010000
3.000
0.230
378
O
Bananas
juice
0.010000
1.000
1.000
379
1A
Sugar
beet
molasses
0.010000
0.040
0.020
380
13A
Blackberries
juice
0.092600
1.000
0.280
383
5B
Cabbage
savoy
0.001000
0.025
0.020
384
4B
Celery
juice
0.015200
1.000
0.030
388
15
Corn
grain/
sugar
molasses
0.008500
1.500
0.010
389
O
Cranberries
juice
concentrate
0.001000
3.300
0.390
392
O
Grapes
juice
concentrate
0.010000
3.600
0.080
398
D
Milk
based
water
0.000300
1.000
0.230
402
12
Peaches
juice
0.070000
1.000
0.150
403
O
Peanuts
butter
0.010000
1.890
0.030
404
11
Pears
juice
0.009800
0.370
0.030
405
6B
Peas
succulent/
blackeye/
cowpea
12
Cooked:
NFS
0.130000
0.045
0.020
14
Boiled
0.130000
0.045
0.020
32
Canned:
Cooked
0.012700
0.045
0.010
42
Frozen:
Cooked
0.012700
0.045
0.010
406
O
Pineapples
juice
concentrate
0.053000
0.540
0.500
407
1AB
Radishes
japanese
(daiken)
0.024000
1.000
0.010
408
15
Rice
bran
7.400000
0.400
0.010
410
12
Apricot
juice
0.070000
1.000
0.010
413
6A
Snowpeas
11
Uncooked
0.130000
1.000
0.020
12
Cooked:
NFS
0.130000
1.000
0.020
14
Boiled
0.130000
1.000
0.020
15
Fried
0.130000
1.000
0.020
42
Frozen:
Cooked
0.012700
1.000
0.010
Attachment
2:
Chronic
and
Cancer
Dietary
Exposure
Analysis:
All
Commodities
69
415
9B
Squash
spaghetti
0.006000
1.000
0.110
416
O
Strawberries
juice
0.063800
1.000
0.160
417
O
Sunflower
seeds
0.042000
1.000
0.010
420
10
Tangerines
juice
concentrate
0.006000
4.080
0.010
423
8
Tomatoes
dried
0.004000
0.520
0.150
424
M
Veal
fat
w/
o
bones
0.000300
1.000
0.230
425
M
Veal
lean
(fat
free)
w/
o
bones
0.006300
1.000
0.230
426
M
Veal
kidney
0.017900
1.000
0.230
427
M
Veal
liver
0.006300
1.000
0.230
428
M
Veal
other
organ
meats
0.017900
1.000
0.230
429
M
Veal
dried
0.006300
1.920
0.230
430
M
Veal
meat
byproducts
0.017900
1.000
0.230
431
14
Walnut
oil
0.270000
1.000
0.010
436
9A
Watermelon
juice
0.001900
1.000
0.130
437
15
Wheat
germ
oil
0.001500
0.650
0.010
439
9B
Wintermelon
0.005600
1.000
0.010
441
10
Grapefruit
juice
concentrate
0.006000
4.580
0.040
442
10
Lemons
juice
concentrate
0.006000
6.330
0.030
443
10
Limes
juice
concentrate
0.006000
3.330
0.010
448
10
Grapefruit
peel
0.013000
1.000
0.040
480
O
Plantains
green
0.010000
1.000
1.000
481
O
Plantains
dried
0.010000
3.900
1.000
940
O
Peanuts
hulled
0.010000
1.000
0.030
Attachment
2:
Chronic
and
Cancer
Dietary
Exposure
Analysis:
All
Commodities
70
Chronic
Results
1989
92
Consumption
Data
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
Chronic
analysis
for
CARBARYL
(1989
92
data)
Residue
file
name:
C:\$
MyFiles\
Carbaryl\
Rdf
files\$$$
10chroniccarbarylfinal9.
RS7
Adjustment
factor
#2
used.
Analysis
Date
04
08
2002/
14:
13:
35
Residue
file
dated:
04
08
2002/
14:
12:
04/
8
Reference
dose
(RfD,
Chronic)
=
.01
mg/
kg
bw/
day
===============================================================================
Total
exposure
by
population
subgroup
Total
Exposure
Population
mg/
kg
Percent
of
Subgroup
body
wt/
day
Rfd
U.
S.
Population
(total)
0.000032
0.3%
U.
S.
Population
(spring
season)
0.000031
0.3%
U.
S.
Population
(summer
season)
0.000030
0.3%
U.
S.
Population
(autumn
season)
0.000034
0.3%
U.
S.
Population
(winter
season)
0.000033
0.3%
Northeast
region
0.000039
0.4%
Midwest
region
0.000023
0.2%
Southern
region
0.000035
0.3%
Western
region
0.000031
0.3%
Hispanics
0.000025
0.3%
Non
hispanic
whites
0.000031
0.3%
Non
hispanic
blacks
0.000038
0.4%
Non
hisp/
non
white/
non
black
0.000054
0.5%
All
infants
(<
1
year)
0.000054
0.5%
Nursing
infants
0.000031
0.3%
Non
nursing
infants
0.000063
0.6%
Children
1
6
yrs
0.000057
0.6%
Children
7
12
yrs
0.000036
0.4%
Females
13
19
(not
preg
or
nursing)
0.000019
0.2%
Females
20+
(not
preg
or
nursing)
0.000028
0.3%
Females
13
50
yrs
0.000026
0.3%
Females
13+
(preg/
not
nursing)
0.000031
0.3%
Females
13+
(nursing)
0.000032
0.3%
Males
13
19
yrs
0.000022
0.2%
Males
20+
yrs
0.000031
0.3%
Seniors
55+
0.000031
0.3%
Pacific
Region
0.000033
0.3%
Cancer
Results
1989
92
Consumption
Data
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
Chronic
analysis
for
CARBARYL
(1989
92
data)
Residue
file
name:
C:\$
MyFiles\
Carbaryl\
Rdf
files\$$$
10chroniccarbarylfinal9.
RS7
Adjustment
factor
#2
used.
Analysis
Date
04
08
2002/
14:
13:
17
Residue
file
dated:
04
08
2002/
14:
12:
04/
8
Q*
=
0.000875
===============================================================================
Total
exposure
by
population
subgroup
Total
Exposure
Population
mg/
kg
Lifetime
risk
Subgroup
body
wt/
day
(Q*=
.000875)
U.
S.
Population
(total)
0.000032
2.80E
08
Attachment
2:
Chronic
and
Cancer
Dietary
Exposure
Analysis:
All
Commodities
71
Chronic
Results
1994
98
Consumption
Data
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
Chronic
analysis
for
CARBARYL
(1994
98
data)
Residue
file
name:
C:\$
MyFiles\
Carbaryl\
Rdf
files\$$$
10chroniccarbarylfinal9.
RS7
Adjustment
factor
#2
used.
Analysis
Date
04
08
2002/
14:
15:
03
Residue
file
dated:
04
08
2002/
14:
12:
04/
8
Reference
dose
(RfD,
Chronic)
=
.01
mg/
kg
bw/
day
===============================================================================
Total
exposure
by
population
subgroup
Total
Exposure
Population
mg/
kg
Percent
of
Subgroup
body
wt/
day
Rfd
U.
S.
Population
(total)
0.000035
0.3%
U.
S.
Population
(spring
season)
0.000035
0.3%
U.
S.
Population
(summer
season)
0.000033
0.3%
U.
S.
Population
(autumn
season)
0.000036
0.4%
U.
S.
Population
(winter
season)
0.000035
0.4%
Northeast
region
0.000042
0.4%
Midwest
region
0.000028
0.3%
Southern
region
0.000033
0.3%
Western
region
0.000038
0.4%
Hispanics
0.000033
0.3%
Non
hispanic
whites
0.000032
0.3%
Non
hispanic
blacks
0.000043
0.4%
Non
hisp/
non
white/
non
black
0.000060
0.6%
All
infants
(<
1
year)
0.000059
0.6%
Nursing
infants
0.000038
0.4%
Non
nursing
infants
0.000067
0.7%
Children
1
6
yrs
0.000074
0.7%
Children
7
12
yrs
0.000034
0.3%
Females
13
19
(not
preg
or
nursing)
0.000021
0.2%
Females
20+
(not
preg
or
nursing)
0.000029
0.3%
Females
13
50
yrs
0.000028
0.3%
Females
13+
(preg/
not
nursing)
0.000028
0.3%
Females
13+
(nursing)
0.000031
0.3%
Males
13
19
yrs
0.000026
0.3%
Males
20+
yrs
0.000032
0.3%
Seniors
55+
0.000030
0.3%
Cancer
Results
1994
98
Consumption
Data
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
Chronic
analysis
for
CARBARYL
(1994
98
data)
Residue
file
name:
C:\$
MyFiles\
Carbaryl\
Rdf
files\$$$
10chroniccarbarylfinal9.
RS7
Adjustment
factor
#2
used.
Analysis
Date
04
08
2002/
14:
15:
14
Residue
file
dated:
04
08
2002/
14:
12:
04/
8
Q*
=
0.000875
===============================================================================
Total
exposure
by
population
subgroup
Total
Exposure
Population
mg/
kg
Lifetime
risk
Subgroup
body
wt/
day
(Q*=
.000875)
U.
S.
Population
(total)
0.000035
3.04E
08
Attachment
3:
Acute
Dietary
Exposure
Analysis:
All
Commodities
72
Residue
File
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
Acute
analysis
for
CARBARYL
Residue
file
name:
C:\$
MyFiles\
Carbaryl\
Rdf
files\$$$
10carbarylfinal9.
RS7
Analysis
Date
04
15
2002
Residue
file
dated:
04
02
2002/
14:
55:
15/
8
Reference
dose
(aRfD)
=
0.01
mg/
kg
bw/
day
RDL
indices
and
parameters
for
Monte
Carlo
Analysis:
Index
Dist
Parameter
#1
Param
#2
Param
#3
Comment
#
Code
1
6
Gardenbeet.
rdf
2
6
Carrot.
rdf
3
6
chic
hors
parsnip
salsify.
rdf
4
6
Potato.
rdf
5
6
radishes.
rdf
6
6
Turnip.
rdf
7
6
sweetpotato.
rdf
8
6
topsgardenbeet.
rdf
9
6
topsradish.
rdf
10
6
Topsturnip.
rdf
11
6
celery.
rdf
12
6
spinach.
rdf
13
6
cannedspinach.
rdf
14
6
lettucehd.
rdf
15
6
lettuceleaf.
rdf
16
6
rhubarb.
rdf
17
6
broccoli.
rdf
18
6
brusselssprouts.
rdf
19
6
cabbage.
rdf
20
6
cauliflower.
rdf
21
6
collards.
rdf
22
6
mustards.
rdf
23
6
kohrabi.
rdf
24
6
beanssucculentfresh.
rdf
25
6
beanssucculentprocessed.
rdf
26
6
beanslima.
rdf
27
6
Peasfresh.
rdf
28
6
Peasprocessed.
rdf
29
6
alleggplant.
rdf
30
6
peppersnonbell.
rdf
31
6
allsweetpepper.
rdf
32
6
tomatoesPB.
rdf
33
6
tomatoesNB.
rdf
34
6
allcucumber.
rdf
35
6
melon.
rdf
36
6
cantaloupe.
rdf
37
6
honeydew.
rdf
38
6
allwatermelon.
rdf
39
6
pumpkin.
rdf
40
6
wintersquash.
rdf
41
6
allsummersquash.
rdf
42
6
citrus.
rdf
43
6
grapefruitjuice.
rdf
44
6
lemonjuice.
rdf
45
6
orangesdecomp.
rdf
46
6
limejuice.
rdf
47
6
orangejuice.
rdf
48
6
appledecomp.
rdf
49
6
apple.
rdf
50
6
applejuice.
rdf
51
6
peardecomp.
rdf
52
6
pear.
rdf
53
6
quince.
rdf
54
6
crabapple.
rdf
55
6
apricot.
rdf
56
6
Apricotss.
rdf
57
6
allsweetcherries.
rdf
58
6
alltartcherries.
rdf
59
6
nectarine.
rdf
60
6
peachSS.
rdf
61
6
Peach.
rdf
62
6
plum2.
rdf
63
6
blackberries.
rdf
64
6
allblueberry.
rdf
65
6
boysenberry.
rdf
66
6
currant.
rdf
Attachment
3:
Acute
Dietary
Exposure
Analysis:
All
Commodities
73
67
6
allraspberries.
rdf
68
6
almonds.
rdf
69
6
chestnut.
rdf
70
6
filbert.
rdf
71
6
pecan.
rdf
72
6
walnut.
rdf
73
6
corn.
rdf
74
6
allasparagus.
rdf
75
6
banana.
rdf
76
6
allcranberry.
rdf
77
6
grapes.
rdf
78
6
grapejuice.
rdf
79
6
okra.
rdf
80
6
olives.
rdf
81
6
pineappledecomp.
rdf
82
6
pineapplemexico.
rdf
83
6
pistachio.
rdf
84
6
strawberrypdp.
rdf
85
6
sunflower.
rdf
86
6
milk2.
rdf
87
6
ruminantliver2.
rdf
88
6
ruminantkidney2.
rdf
89
6
swinemeat2.
rdf
90
6
swinefat2.
rdf
91
6
swineliver2.
rdf
92
6
swinekidney2.
rdf
93
6
poultry.
rdf
94
6
eggs.
rdf
95
6
pineappleother.
rdf
96
6
Plumdecomp.
rdf
97
6
pineappledomestic.
rdf
98
6
appledried.
rdf
99
6
soybean.
rdf
100
6
wheat.
rdf
Food
Crop
Food
Def
Res
Adj.
Factors
RDL
Indices
and
Ratios
Code
Grp
Name
(ppm)
#1
#2
I#
1
Ratio#
1
I#
2
Ratio#
2
I#
3
Ratio#
3
1
13A
Blackberries
1.000000
1.000
1.000
63
1.0000
2
13A
Boysenberries
1.000000
1.000
1.000
65
1.0000
3
13A
Dewberries
1.000000
1.000
1.000
65
1.0000
4
13A
Loganberries
1.000000
1.000
1.000
65
1.0000
5
13A
Raspberries
1.000000
1.000
1.000
67
1.0000
6
13A
Youngberries
1.000000
1.000
1.000
65
1.0000
7
13B
Blueberries
1.000000
1.000
1.000
64
1.0000
8
O
Cranberries
1.000000
1.000
1.000
76
1.0000
9
O
Cranberries
juice
1.000000
1.100
1.000
76
1.0000
10
13B
Currants
1.000000
1.000
1.000
66
1.0000
11
13B
Elderberries
1.000000
1.000
1.000
66
1.0000
12
13B
Gooseberries
1.000000
1.000
1.000
66
1.0000
13
O
Grapes
1.000000
1.000
1.000
77
1.0000
14
O
Grapes
raisins
11
Uncooked
1.000000
2.170
1.000
77
1.0000
12
Cooked:
NFS
1.000000
1.370
1.000
77
1.0000
13
Baked
1.000000
1.370
1.000
77
1.0000
14
Boiled
1.000000
1.370
1.000
77
1.0000
18
Dried
1.000000
1.370
1.000
77
1.0000
42
Frozen:
Cooked
Attachment
3:
Acute
Dietary
Exposure
Analysis:
All
Commodities
74
1.000000
1.370
1.000
77
1.0000
15
O
Grapes
juice
1.000000
1.000
1.000
78
1.0000
16
13B
Huckleberries
1.000000
1.000
1.000
66
1.0000
17
O
Strawberries
1.000000
1.000
1.000
84
1.0000
20
10
Citrus
citron
1.000000
1.000
1.000
42
1.0000
22
10
Grapefruit
peeled
fruit
11
Uncooked
1.000000
1.000
1.000
45
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
45
1.0000
14
Boiled
0.000000
1.000
1.000
31
Canned:
NFS
1.000000
1.000
1.000
42
1.0000
23
10
Grapefruit
juice
1.000000
1.170
1.000
43
1.0000
24
10
Kumquats
1.000000
1.000
1.000
42
1.0000
26
10
Lemons
peeled
fruit
11
Uncooked
1.000000
1.000
1.000
45
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
45
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
42
1.0000
27
10
Lemons
peel
1.000000
1.190
1.000
42
1.0000
28
10
Lemons
juice
1.000000
1.110
1.000
44
1.0000
30
10
Limes
peeled
fruit
1.000000
1.000
1.000
45
1.0000
31
10
Limes
peel
1.000000
1.270
1.000
42
1.0000
32
10
Limes
juice
1.000000
1.110
1.000
46
1.0000
33
10
Oranges
juice
concentrate
1.000000
3.700
1.000
47
1.0000
34
10
Oranges
peeled
fruit
11
Uncooked
1.000000
1.000
1.000
45
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
45
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
42
1.0000
35
10
Oranges
peel
1.000000
1.270
1.000
42
1.0000
36
10
Oranges
juice
1.000000
1.000
1.000
47
1.0000
37
10
Tangelos
1.000000
1.000
1.000
45
1.0000
38
10
Tangerines
11
Uncooked
1.000000
1.000
1.000
45
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
42
1.0000
41
Frozen:
NFS
1.000000
1.000
1.000
42
1.0000
39
10
Tangerines
juice
1.000000
1.280
1.000
46
1.0000
40
14
Almonds
1.000000
1.000
1.000
68
1.0000
43
14
Chestnuts
1.000000
1.000
1.000
69
1.0000
44
14
Filberts
(hazelnuts)
1.000000
1.000
1.000
70
1.0000
48
14
Walnuts
1.000000
1.000
1.000
72
1.0000
50
O
Pistachio
nuts
1.000000
1.000
1.000
83
1.0000
52
11
Apples
11
Uncooked
1.000000
1.000
1.000
48
1.0000
Attachment
3:
Acute
Dietary
Exposure
Analysis:
All
Commodities
75
12
Cooked:
NFS
1.000000
1.000
1.000
48
1.0000
13
Baked
1.000000
1.000
1.000
48
1.0000
14
Boiled
1.000000
1.000
1.000
48
1.0000
15
Fried
1.000000
1.000
1.000
48
1.0000
18
Dried
0.009000
1.000
1.000
98
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
49
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
49
1.0000
33
Canned:
Baked
1.000000
1.000
1.000
49
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
49
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
49
1.0000
53
11
Apples
dried
1.000000
2.600
1.000
49
1.0000
54
11
Apples
juice/
cider
1.000000
1.000
1.000
50
1.0000
55
11
Crabapples
1.000000
1.000
1.000
54
1.0000
56
11
Pears
11
Uncooked
1.000000
1.000
1.000
51
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
51
1.0000
13
Baked
1.000000
1.000
1.000
51
1.0000
14
Boiled
1.000000
1.000
1.000
51
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
52
1.0000
57
11
Pears
dried
1.000000
2.600
1.000
52
1.0000
58
11
Quinces
1.000000
1.000
1.000
53
1.0000
59
12
Apricots
11
Uncooked
1.000000
1.000
1.000
56
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
56
1.0000
14
Boiled
1.000000
1.000
1.000
56
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
55
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
55
1.0000
60
12
Apricots
dried
1.000000
6.000
1.000
55
1.0000
61
12
Cherries
11
Uncooked
1.000000
1.000
1.000
57
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
58
1.0000
13
Baked
1.000000
1.000
1.000
58
1.0000
14
Boiled
1.000000
1.000
1.000
58
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
58
1.0000
33
Canned:
Baked
1.000000
1.000
1.000
58
1.0000
41
Frozen:
NFS
1.000000
1.000
1.000
58
1.0000
62
12
Cherries
dried
1.000000
4.000
1.000
57
1.0000
63
12
Cherries
juice
1.000000
1.500
1.000
58
1.0000
64
12
Nectarines
1.000000
1.000
1.000
59
1.0000
65
12
Peaches
Attachment
3:
Acute
Dietary
Exposure
Analysis:
All
Commodities
76
11
Uncooked
1.000000
1.000
1.000
60
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
60
1.0000
13
Baked
1.000000
1.000
1.000
60
1.0000
14
Boiled
1.000000
1.000
1.000
60
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
61
1.0000
41
Frozen:
NFS
1.000000
1.000
1.000
61
1.0000
66
12
Peaches
dried
1.000000
7.000
1.000
61
1.0000
67
12
Plums
(damsons)
11
Uncooked
1.000000
1.000
1.000
96
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
96
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
62
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
62
1.0000
51
Cured:
NFS
(smoked/
p
1.000000
1.000
1.000
62
1.0000
68
12
Plums
prunes
(dried)
1.000000
0.150
1.000
62
1.0000
69
12
Plums/
prune
juice
1.000000
1.400
1.000
62
1.0000
72
O
Bananas
1.000000
1.000
1.000
75
1.0000
73
O
Bananas
dried
1.000000
3.900
1.000
75
1.0000
81
11
Loquats
1.000000
1.000
1.000
53
1.0000
82
O
Olives
1.000000
1.000
1.000
80
1.0000
89
O
Pineapples
peeled
fruit
11
Uncooked
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
12
Cooked:
NFS
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
13
Baked
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
14
Boiled
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
31
Canned:
NFS
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
33
Canned:
Baked
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
41
Frozen:
NFS
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
90
O
Pineapples
dried
1.000000
5.000
1.000
82
0.0250
95
0.4750
97
0.5000
91
O
Pineapples
juice
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
94
O
Plantains
ripe
1.000000
1.000
1.000
75
1.0000
123
19A
Dill
0.004000
1.000
1.000
126
1AB
Horseradish
1.000000
1.000
1.000
3
1.0000
139
8
Paprika
1.000000
1.000
1.000
30
1.0000
141
9A
Melons
cantaloupes
juice
1.000000
1.000
1.000
36
1.0000
142
9A
Melons
cantaloupes
pulp
1.000000
1.000
1.000
36
1.0000
143
9A
Casabas
1.000000
1.000
1.000
35
1.0000
144
9A
Crenshaws
1.000000
1.000
1.000
35
1.0000
145
9A
Melons
honeydew
1.000000
1.000
1.000
37
1.0000
146
9A
Melons
persian
1.000000
1.000
1.000
35
1.0000
Attachment
3:
Acute
Dietary
Exposure
Analysis:
All
Commodities
77
147
9A
Watermelon
1.000000
1.000
1.000
38
1.0000
148
9B
Cucumbers
1.000000
1.000
1.000
34
1.0000
149
9B
Pumpkin
1.000000
1.000
1.000
39
1.0000
150
9B
Squash
summer
1.000000
1.000
1.000
41
1.0000
151
9B
Squash
winter
1.000000
1.000
1.000
40
1.0000
152
9B
Bitter
melon
1.000000
1.000
1.000
35
1.0000
154
8
Eggplant
1.000000
1.000
1.000
29
1.0000
155
8
Peppers
sweet(
garden)
1.000000
1.000
1.000
31
1.0000
156
8
Peppers
chilli
incl
jalapeno
1.000000
1.000
1.000
30
1.0000
157
8
Peppers
other
1.000000
1.000
1.000
30
1.0000
158
8
Pimientos
1.000000
1.000
1.000
30
1.0000
159
8
Tomatoes
whole
11
Uncooked
1.000000
1.000
1.000
33
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
33
1.0000
13
Baked
1.000000
1.000
1.000
33
1.0000
14
Boiled
1.000000
1.000
1.000
33
1.0000
15
Fried
1.000000
1.000
1.000
33
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
32
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
32
1.0000
33
Canned:
Baked
1.000000
1.000
1.000
32
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
32
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
32
1.0000
160
8
Tomatoes
juice
1.000000
0.540
1.000
32
1.0000
161
8
Tomatoes
puree
1.000000
0.650
1.000
32
1.0000
162
8
Tomatoes
paste
1.000000
0.650
1.000
32
1.0000
163
8
Tomatoes
catsup
1.000000
0.650
1.000
32
1.0000
165
2
Beets
garden
tops(
greens)
1.000000
1.000
1.000
8
1.0000
166
4B
Celery
1.000000
1.000
1.000
11
1.0000
168
5A
Broccoli
1.000000
1.000
1.000
17
1.0000
169
5A
Brussels
sprouts
1.000000
1.000
1.000
18
1.0000
170
5A
Cabbage
green
and
red
11
Uncooked
1.000000
0.250
1.000
19
1.0000
12
Cooked:
NFS
1.000000
0.025
1.000
19
1.0000
13
Baked
1.000000
0.025
1.000
19
1.0000
14
Boiled
1.000000
0.025
1.000
19
1.0000
15
Fried
1.000000
0.025
1.000
19
1.0000
31
Canned:
NFS
1.000000
0.250
1.000
19
1.0000
32
Canned:
Cooked
1.000000
0.025
1.000
19
1.0000
51
Cured:
NFS
(smoked/
p
1.000000
0.025
1.000
19
1.0000
Attachment
3:
Acute
Dietary
Exposure
Analysis:
All
Commodities
78
171
5A
Cauliflower
1.000000
1.000
1.000
20
1.0000
172
5B
Collards
1.000000
1.000
1.000
21
1.0000
174
5B
Kale
1.000000
1.000
1.000
22
1.0000
175
5A
Kohlrabi
1.000000
1.000
1.000
23
1.0000
176
4A
Lettuce
leafy
varieties
1.000000
1.000
1.000
15
1.0000
177
4A
Dandelion
greens
1.000000
1.000
1.000
12
1.0000
178
4A
Endive
curley
and
escarole
1.000000
1.000
1.000
15
1.0000
182
4A
Lettuce
unspecified
1.000000
1.000
1.000
14
1.0000
183
5B
Mustard
greens
1.000000
1.000
1.000
22
1.0000
184
4A
Parsley
1.000000
1.000
1.000
12
1.0000
185
4B
Rhubarb
1.000000
1.000
1.000
16
1.0000
186
4A
Spinach
11
Uncooked
1.000000
1.000
1.000
12
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
12
1.0000
13
Baked
0.000000
1.000
1.000
14
Boiled
1.000000
1.000
1.000
12
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
13
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
13
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
13
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
12
1.0000
44
Frozen:
Boiled
1.000000
1.000
1.000
12
1.0000
187
4B
Swiss
chard
1.000000
1.000
1.000
16
1.0000
188
2
Turnips
tops
1.000000
1.000
1.000
10
1.0000
192
4A
Lettuce
head
varieties
1.000000
1.000
1.000
14
1.0000
195
O
Grapes
leaves
1.000000
1.000
1.000
77
1.0000
197
1AB
Beets
garden
roots
1.000000
1.000
1.000
1
1.0000
198
1AB
Carrots
1.000000
1.000
1.000
2
1.0000
207
1C
Potatoes/
white
whole
11
Uncooked
1.000000
1.000
1.000
4
1.0000
12
Cooked:
NFS
1.000000
0.040
1.000
4
1.0000
13
Baked
1.000000
1.200
1.000
4
1.0000
14
Boiled
1.000000
2.500
1.000
4
1.0000
15
Fried
1.000000
0.040
1.000
4
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
4
1.0000
208
1C
Potatoes/
white
unspecified
1.000000
1.000
1.000
4
1.0000
209
1C
Potatoes/
white
peeled
11
Uncooked
0.000000
1.000
1.000
12
Cooked:
NFS
1.000000
1.000
1.000
4
1.0000
13
Baked
1.000000
1.200
1.000
4
1.0000
14
Boiled
Attachment
3:
Acute
Dietary
Exposure
Analysis:
All
Commodities
79
1.000000
2.500
1.000
4
1.0000
15
Fried
1.000000
0.040
1.000
4
1.0000
31
Canned:
NFS
0.000000
1.000
1.000
32
Canned:
Cooked
1.000000
1.000
1.000
4
1.0000
34
Canned:
Boiled
1.000000
2.500
1.000
4
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
4
1.0000
43
Frozen:
Baked
1.000000
1.200
1.000
4
1.0000
45
Frozen:
Fried
1.000000
0.040
1.000
4
1.0000
210
1C
Potatoes/
white
dry
0.000357
0.020
1.000
211
1C
Potatoes/
white
peel
only
13
Baked
1.000000
1.200
1.000
4
1.0000
15
Fried
1.000000
0.040
1.000
4
1.0000
212
1AB
Radishes
roots
1.000000
1.000
1.000
5
1.0000
213
2
Radishes
tops
1.000000
1.000
1.000
9
1.0000
214
1AB
Rutabagas
roots
1.000000
1.000
1.000
6
1.0000
215
2
Rutabagas
tops
1.000000
1.000
1.000
10
1.0000
216
1AB
Salsify(
oyster
plant)
1.000000
1.000
1.000
3
1.0000
218
1CD
Sweet
potatoes
(incl
yams)
1.000000
1.000
1.000
7
1.0000
219
1AB
Turnips
roots
1.000000
1.000
1.000
6
1.0000
220
1AB
Parsnips
1.000000
1.000
1.000
3
1.0000
227
6C
Beans
dry
great
northern
0.002000
1.000
1.000
228
6C
Beans
dry
kidney
0.002000
1.000
1.000
229
6C
Beans
dry
lima
0.002000
1.000
1.000
230
6C
Beans
dry
navy
(pea)
0.002000
1.000
1.000
231
6C
Beans
dry
other
0.002000
1.000
1.000
232
6C
Beans
dry
pinto
0.002000
1.000
1.000
233
6B
Beans
succulent
lima
1.000000
1.000
1.000
26
1.0000
234
6A
Beans
succulent
green
11
Uncooked
1.000000
1.000
1.000
24
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
24
1.0000
14
Boiled
1.000000
1.000
1.000
24
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
25
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
25
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
25
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
25
1.0000
44
Frozen:
Boiled
1.000000
1.000
1.000
25
1.0000
51
Cured:
NFS
(smoked/
p
1.000000
1.000
1.000
25
1.0000
235
6A
Beans
succulent
other
1.000000
1.000
1.000
25
1.0000
236
6A
Beans
succulent
yellow/
wax
14
Boiled
1.000000
1.000
1.000
24
1.0000
Attachment
3:
Acute
Dietary
Exposure
Analysis:
All
Commodities
80
32
Canned:
Cooked
1.000000
1.000
1.000
25
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
25
1.0000
237
15
Corn/
pop
0.000100
1.000
1.000
238
15
Corn/
sweet
1.000000
1.000
1.000
73
1.0000
240
6C
Peas
(garden)
dry
0.013000
0.045
1.000
241
6AB
Peas
(garden)
green
11
Uncooked
1.000000
1.000
1.000
27
1.0000
12
Cooked:
NFS
1.000000
0.150
1.000
27
1.0000
13
Baked
1.000000
0.150
1.000
27
1.0000
14
Boiled
1.000000
0.150
1.000
27
1.0000
15
Fried
1.000000
0.150
1.000
27
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
28
1.0000
32
Canned:
Cooked
1.000000
0.150
1.000
28
1.0000
34
Canned:
Boiled
1.000000
0.150
1.000
28
1.0000
42
Frozen:
Cooked
1.000000
0.150
1.000
28
1.0000
44
Frozen:
Boiled
1.000000
0.150
1.000
28
1.0000
45
Frozen:
Fried
1.000000
0.150
1.000
28
1.0000
243
6C
Lentils
0.002000
1.000
1.000
244
6C
Mung
beans
(sprouts)
0.002000
1.000
1.000
245
O
Okra
12
Cooked:
NFS
1.000000
0.180
1.000
79
1.0000
14
Boiled
1.000000
0.050
1.000
79
1.0000
15
Fried
1.000000
0.180
1.000
79
1.0000
32
Canned:
Cooked
1.000000
0.180
1.000
79
1.0000
42
Frozen:
Cooked
1.000000
0.180
1.000
79
1.0000
44
Frozen:
Boiled
1.000000
0.050
1.000
79
1.0000
249
6C
Beans
dry
broadbeans
0.002000
1.000
1.000
250
6B
Beans
succulent
broadbeans
1.000000
1.000
1.000
24
1.0000
251
6C
Beans
dry
pigeon
beans
0.002000
1.000
1.000
253
6
Beans
unspecified
1.000000
1.000
1.000
24
1.0000
255
6A
Soybeans
sprouted
seeds
0.000015
0.330
1.000
99
1.0000
256
O
Beans
dry
hyacinth
0.002000
1.000
1.000
257
O
Beans
succulent
hyacinth
1.000000
1.000
1.000
24
1.0000
258
6C
Beans
dry
blackeye
peas/
cowpea
0.002000
1.000
1.000
259
6C
Beans
dry
garbanzo/
chick
pea
0.002000
1.000
1.000
260
O
Asparagus
1.000000
1.000
1.000
74
1.0000
266
15
Corn
grain
endosperm
0.000100
1.000
1.000
267
15
Corn
grain
bran
0.000100
1.000
1.000
268
15
Corn
grain/
sugar/
hfcs
0.000100
1.500
1.000
Attachment
3:
Acute
Dietary
Exposure
Analysis:
All
Commodities
81
270
15
Rice
rough
(brown)
0.074000
1.000
1.000
271
15
Rice
milled
(white)
0.074000
0.030
1.000
275
15
Sorghum
(including
milo)
0.000015
1.000
1.000
100
1.0000
276
15
Wheat
rough
0.000015
1.000
1.000
100
1.0000
277
15
Wheat
germ
0.000015
1.000
1.000
278
15
Wheat
bran
0.000015
1.000
1.000
279
15
Wheat
flour
0.000015
1.000
1.000
280
15
Millet
0.000015
1.000
1.000
100
1.0000
282
1A
Sugar
beet
0.000400
0.040
1.000
287
6C
Guar
beans
1.000000
1.000
1.000
24
1.0000
289
15
Corn
grain
oil
0.000100
0.250
1.000
292
O
Flax
seed
0.000100
1.000
1.000
293
O
Peanuts
oil
0.000600
0.290
1.000
297
6A
Soybeans
oil
0.000015
0.010
1.000
298
O
Sunflower
oil
0.000400
0.670
1.000
300
O
Olive
oil
0.077000
0.810
1.000
303
6A
Soybean
other
0.000015
1.000
1.000
99
1.0000
304
6A
Soybeans
mature
seeds
dry
0.000015
1.000
1.000
99
1.0000
305
6A
Soybeans
flour
(full
fat)
0.000015
1.000
1.000
306
6A
Soybeans
flour
(low
fat)
0.000015
1.000
1.000
307
6A
Soybeans
flour
(defatted)
0.000015
1.000
1.000
315
O
Grapes
wine
and
sherry
1.000000
1.000
1.000
77
1.0000
318
D
Milk
nonfat
solids
0.030000
1.000
1.000
86
1.0000
319
D
Milk
fat
solids
0.030000
1.000
1.000
86
1.0000
320
D
Milk
sugar
(lactose)
0.030000
1.000
1.000
86
1.0000
321
M
Beef
meat
byproducts
3.675000
1.000
1.000
88
1.0000
322
M
Beef
other
organ
meats
3.675000
1.000
1.000
88
1.0000
323
M
Beef
dried
0.907000
1.920
1.000
86
1.0000
324
M
Beef
fat
w/
o
bones
0.368000
1.000
1.000
86
1.0000
325
M
Beef
kidney
3.675000
1.000
1.000
88
1.0000
326
M
Beef
liver
1.390000
1.000
1.000
87
1.0000
327
M
Beef
lean
(fat/
free)
w/
o
bones
0.907000
1.000
1.000
86
1.0000
328
M
Goat
meat
byproducts
3.675000
1.000
1.000
88
1.0000
329
M
Goat
other
organ
meats
3.675000
1.000
1.000
88
1.0000
330
M
Goat
fat
w/
o
bone
0.368000
1.000
1.000
86
1.0000
331
M
Goat
kidney
3.675000
1.000
1.000
88
1.0000
332
M
Goat
liver
1.390000
1.000
1.000
87
1.0000
333
M
Goat
lean
(fat/
free)
w/
o
bone
0.907000
1.000
1.000
86
1.0000
Attachment
3:
Acute
Dietary
Exposure
Analysis:
All
Commodities
82
336
M
Sheep
meat
byproducts
3.675000
1.000
1.000
88
1.0000
337
M
Sheep
other
organ
meats
3.675000
1.000
1.000
88
1.0000
338
M
Sheep
fat
w/
o
bone
0.368000
1.000
1.000
86
1.0000
339
M
Sheep
kidney
3.675000
1.000
1.000
88
1.0000
340
M
Sheep
liver
1.390000
1.000
1.000
87
1.0000
341
M
Sheep
lean
(fat
free)
w/
o
bone
0.907000
1.000
1.000
86
1.0000
342
M
Pork
meat
byproducts
0.260000
1.000
1.000
92
1.0000
343
M
Pork
other
organ
meats
0.260000
1.000
1.000
92
1.0000
344
M
Pork
fat
w/
o
bone
0.026000
1.000
1.000
90
1.0000
345
M
Pork
kidney
0.260000
1.000
1.000
92
1.0000
346
M
Pork
liver
0.100000
1.000
1.000
91
1.0000
347
M
Pork
lean
(fat
free)
w/
o
bone
0.065000
1.000
1.000
89
1.0000
349
F
Fish
shellfish
0.250000
1.000
1.000
377
11
Apples
juice
concentrate
1.000000
3.000
1.000
50
1.0000
378
O
Bananas
juice
1.000000
1.000
1.000
75
1.0000
379
1A
Sugar
beet
molasses
0.000400
0.040
1.000
380
13A
Blackberries
juice
1.000000
1.000
1.000
63
1.0000
383
5B
Cabbage
savoy
12
Cooked:
NFS
1.000000
0.025
1.000
19
1.0000
384
4B
Celery
juice
1.000000
1.000
1.000
11
1.0000
388
15
Corn
grain/
sugar
molasses
0.000100
1.500
1.000
389
O
Cranberries
juice
concentrate
1.000000
3.300
1.000
76
1.0000
392
O
Grapes
juice
concentrate
1.000000
3.000
1.000
78
1.0000
398
D
Milk
based
water
0.030000
1.000
1.000
86
1.0000
402
12
Peaches
juice
1.000000
1.000
1.000
61
1.0000
403
O
Peanuts
butter
0.000600
1.890
1.000
404
11
Pears
juice
1.000000
0.370
1.000
52
1.0000
405
6B
Peas
succulent/
blackeye/
cowpea
12
Cooked:
NFS
1.000000
0.150
1.000
27
1.0000
14
Boiled
1.000000
0.150
1.000
27
1.0000
32
Canned:
Cooked
1.000000
0.150
1.000
28
1.0000
42
Frozen:
Cooked
1.000000
0.150
1.000
28
1.0000
406
O
Pineapples
juice
concentrate
1.000000
2.000
1.000
82
0.0250
95
0.4750
97
0.5000
407
1AB
Radishes
japanese
(daiken)
1.000000
1.000
1.000
5
1.0000
408
15
Rice
bran
0.074000
0.400
1.000
410
12
Apricot
juice
1.000000
1.000
1.000
55
1.0000
413
6A
Snowpeas
11
Uncooked
1.000000
1.000
1.000
27
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
27
1.0000
14
Boiled
Attachment
3:
Acute
Dietary
Exposure
Analysis:
All
Commodities
83
1.000000
1.000
1.000
27
1.0000
15
Fried
1.000000
1.000
1.000
27
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
28
1.0000
415
9B
Squash
spaghetti
1.000000
1.000
1.000
40
1.0000
416
O
Strawberries
juice
1.000000
1.000
1.000
84
1.0000
417
O
Sunflower
seeds
1.000000
1.000
1.000
85
1.0000
420
10
Tangerines
juice
concentrate
1.000000
4.080
1.000
46
1.0000
423
8
Tomatoes
dried
1.000000
0.520
1.000
32
1.0000
424
M
Veal
fat
w/
o
bones
0.368000
1.000
1.000
86
1.0000
425
M
Veal
lean
(fat
free)
w/
o
bones
0.907000
1.000
1.000
86
1.0000
426
M
Veal
kidney
3.675000
1.000
1.000
88
1.0000
427
M
Veal
liver
1.390000
1.000
1.000
87
1.0000
428
M
Veal
other
organ
meats
3.675000
1.000
1.000
88
1.0000
429
M
Veal
dried
0.907000
1.920
1.000
86
1.0000
430
M
Veal
meat
byproducts
3.675000
1.000
1.000
88
1.0000
431
14
Walnut
oil
0.005400
1.000
1.000
436
9A
Watermelon
juice
1.000000
1.000
1.000
38
1.0000
437
15
Wheat
germ
oil
0.000015
1.000
1.000
439
9B
Wintermelon
1.000000
1.000
1.000
35
1.0000
441
10
Grapefruit
juice
concentrate
1.000000
4.580
1.000
43
1.0000
442
10
Lemons
juice
concentrate
1.000000
6.330
1.000
44
1.0000
443
10
Limes
juice
concentrate
1.000000
3.330
1.000
46
1.0000
448
10
Grapefruit
peel
1.000000
1.000
1.000
42
1.0000
480
O
Plantains
green
1.000000
1.000
1.000
75
1.0000
481
O
Plantains
dried
1.000000
3.900
1.000
75
1.0000
940
O
Peanuts
hulled
0.000600
1.000
1.000
Attachment
3:
Acute
Dietary
Exposure
Analysis:
All
Commodities
84
Results
1989
1992
Consumption
data
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
ACUTE
Analysis
for
CARBARYL
(1989
92
data)
Residue
file:
$$$
10carbarylfinal9.
RS7
Adjustment
factor
#2
NOT
used.
Analysis
Date:
04
02
2002/
15:
44:
07
Residue
file
dated:
04
02
2002/
14:
55:
15/
8
Daily
totals
for
food
and
foodform
consumption
used.
MC
iterations
=
1000
MC
list
in
residue
file
MC
seed
=
10
Run
Comment:
""
===============================================================================
Summary
calculations
(per
capita):
95th
Percentile
99th
Percentile
99.9th
Percentile
Exposure
%
aRfD
Exposure
%
aRfD
Exposure
%
aRfD
U.
S.
Population:
0.000505
5.05
0.001381
13.81
0.005989
59.89
All
infants:
0.000864
8.64
0.003683
36.83
0.013251
132.51
Nursing
infants
(<
1
yr
old):
0.000283
2.83
0.001208
12.08
0.007703
77.03
Non
nursing
infants
(<
1
yr
old):
0.001198
11.98
0.004263
42.63
0.014013
140.13
Children
1
6
yrs:
0.001309
13.09
0.002552
25.52
0.010974
109.74
Children
7
12
yrs:
0.000722
7.22
0.001644
16.44
0.008721
87.21
Females
13+
(preg/
not
nursing):
0.000442
4.42
0.000989
9.89
0.006103
61.03
Females
13+
(nursing):
0.000486
4.86
0.001408
14.08
0.008584
85.84
Females
13
19
(not
preg
or
nursing):
0.000335
3.35
0.000864
8.64
0.004530
45.30
Females
20+
(not
preg
or
nursing):
0.000299
2.99
0.000967
9.67
0.004767
47.67
Females
13
50
yrs:
0.000318
3.18
0.000918
9.18
0.004444
44.44
Males
13
19
yrs:
0.000428
4.28
0.000899
8.99
0.003596
35.96
Males
20+
yrs:
0.000318
3.18
0.000929
9.29
0.004223
42.23
Seniors
55+:
0.000307
3.07
0.001068
10.68
0.005789
57.89
Attachment
3:
Acute
Dietary
Exposure
Analysis:
All
Commodities
85
Results
1994
1996
Consumption
data
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
ACUTE
Analysis
for
CARBARYL
(1994
98
data)
Residue
file:
$$$
10carbarylfinal9.
RS7
Adjustment
factor
#2
NOT
used.
Analysis
Date:
04
02
2002/
16:
52:
44
Residue
file
dated:
04
02
2002/
14:
55:
15/
8
Daily
totals
for
food
and
foodform
consumption
used.
MC
iterations
=
1000
MC
list
in
residue
file
MC
seed
=
10
Run
Comment:
""
===============================================================================
Summary
calculations
(per
capita):
95th
Percentile
99th
Percentile
99.9th
Percentile
Exposure
%
aRfD
Exposure
%
aRfD
Exposure
%
aRfD
U.
S.
Population:
0.000508
5.08
0.001467
14.67
0.006150
61.50
All
infants:
0.000922
9.22
0.004027
40.27
0.013420
134.20
Nursing
infants
(<
1
yr
old):
0.000412
4.12
0.002251
22.51
0.010542
105.42
Non
nursing
infants
(<
1
yr
old):
0.001165
11.65
0.004406
44.06
0.014247
142.47
Children
1
6
yrs:
0.001460
14.60
0.003282
32.82
0.013812
138.12
Children
7
12
yrs:
0.000685
6.85
0.001473
14.73
0.007073
70.73
Females
13+
(preg/
not
nursing):
0.000404
4.04
0.001077
10.77
0.006308
63.08
Females
13+
(nursing):
0.000378
3.78
0.001166
11.66
0.006904
69.04
Females
13
19
(not
preg
or
nursing):
0.000319
3.19
0.000907
9.07
0.004463
44.63
Females
20+
(not
preg
or
nursing):
0.000308
3.08
0.000999
9.99
0.005068
50.68
Females
13
50
yrs:
0.000322
3.22
0.000997
9.97
0.004794
47.94
Males
13
19
yrs:
0.000420
4.20
0.000929
9.29
0.005181
51.81
Males
20+
yrs:
0.000336
3.36
0.000922
9.22
0.003940
39.40
Seniors
55+:
0.000313
3.13
0.001003
10.03
0.005442
54.42
Attachment
4
Acute
Critical
Exposure
Contribution
Analysis
86
U.
S.
Environmental
Protection
Agency
DEEM
Acute
Critical
Exposure
Contribution
Analysis
(Ver
7.76)
CSFII
1989
92
Residue
file
=
C:\$
MyFiles\
Carbaryl\
Rdf
files\$$$
10carbarylfinal9.
RS7
Acute
report
=
C:\$
MyFiles\
Carbaryl\
Rdf
files\$$$
10carbarylfinal9.
AC7
Date
and
time
of
analysis:
04
02
2002
14:
58:
48
Daily
totals
for
food
and
foodform
consumption
used.
Adjustment
factor
#2
not
used.
Minimum
exposure
contribution
=
1%
Monte
Carlo
Iterations
=
1000
Seed
=
10
CEC
records
generated
for
first
111
iterations.
Exposures
divided
by
body
weight
================================================================================
U.
S.
Population
Low
percentile
for
CEC
records:
99.5
Exposure
(mg/
day)
=
0.002066
High
percentile
for
CEC
records:
100
Exposure
(mg/
day)
=
0.697664
Number
of
actual
records
in
this
interval:
21792
Critical
foods/
foodforms
for
this
population
(as
derived
from
these
records):
N=
number
of
appearances
in
all
records
(including
duplicates)
%=
percent
of
total
exposure
for
all
records
(including
duplicates)
Food,
FF,
N
,
Percent,
Food
Name
,
,
,
,
172,
14,
1827,
13.34%,
Collards
Boiled
188,
14,
429,
13.08%,
Turnips
tops
Boiled
52,
11,
2690,
10.12%,
Apples
Uncooked
398,
16,
7643,
9.86%,
Milk
based
water
Pasteurized
52,
14,
1119,
5.13%,
Apples
Boiled
17,
11,
1071,
4.54%,
Strawberries
Uncooked
165,
14,
261,
4.05%,
Beets
garden
tops(
greens)
Boiled
65,
12,
1100,
3.10%,
Peaches
Cooked:
NFS
65,
31,
480,
2.37%,
Peaches
Canned:
NFS
65,
11,
594,
1.70%,
Peaches
Uncooked
349,
12,
598,
1.64%,
Fish
shellfish
Cooked:
NFS
234,
14,
753,
1.55%,
Beans
succulent
green
Boiled
215,
12,
52,
1.51%,
Rutabagas
tops
Cooked:
NFS
54,
11,
1306,
1.46%,
Apples
juice/
cider
Uncooked
64,
11,
251,
1.33%,
Nectarines
Uncooked
326,
15,
446,
1.16%,
Beef
liver
Fried
156,
11,
470,
1.14%,
Peppers
chilli
incl
jalapeno
Uncooked
183,
14,
162,
1.09%,
Mustard
greens
Boiled
69,
11,
263,
1.03%,
Plums/
prune
juice
Uncooked
================================================================================
All
infants
Low
percentile
for
CEC
records:
99.5
Exposure
(mg/
day)
=
0.005300
High
percentile
for
CEC
records:
100
Exposure
(mg/
day)
=
0.101947
Number
of
actual
records
in
this
interval:
367
Critical
foods/
foodforms
for
this
population
(as
derived
from
these
records):
N=
number
of
appearances
in
all
records
(including
duplicates)
%=
percent
of
total
exposure
for
all
records
(including
duplicates)
Food,
FF,
N
,
Percent,
Food
Name
,
,
,
,
65,
31,
179,
49.83%,
Peaches
Canned:
NFS
52,
31,
73,
12.60%,
Apples
Canned:
NFS
398,
16,
95,
10.82%,
Milk
based
water
Pasteurized
52,
14,
14,
4.09%,
Apples
Boiled
183,
14,
4,
3.39%,
Mustard
greens
Boiled
377,
31,
50,
3.12%,
Apples
juice
concentrate
Canned:
NFS
65,
12,
7,
2.97%,
Peaches
Cooked:
NFS
406,
41,
3,
1.90%,
Pineapples
juice
concentrate
Frozen:
NFS
61,
31,
11,
1.49%,
Cherries
Canned:
NFS
89,
31,
7,
1.35%,
Pineapples
peeled
fruit
Canned:
NFS
406,
31,
5,
1.07%,
Pineapples
juice
concentrate
Canned:
NFS
================================================================================
Attachment
4
Acute
Critical
Exposure
Contribution
Analysis
87
Children
1
6
yrs
Low
percentile
for
CEC
records:
99.5
Exposure
(mg/
day)
=
0.003822
High
percentile
for
CEC
records:
100
Exposure
(mg/
day)
=
0.697664
Number
of
actual
records
in
this
interval:
2205
Critical
foods/
foodforms
for
this
population
(as
derived
from
these
records):
N=
number
of
appearances
in
all
records
(including
duplicates)
%=
percent
of
total
exposure
for
all
records
(including
duplicates)
Food,
FF,
N
,
Percent,
Food
Name
,
,
,
,
52,
11,
409,
16.79%,
Apples
Uncooked
52,
14,
264,
13.68%,
Apples
Boiled
188,
14,
25,
9.42%,
Turnips
tops
Boiled
172,
14,
103,
6.90%,
Collards
Boiled
17,
11,
95,
5.76%,
Strawberries
Uncooked
398,
16,
698,
4.60%,
Milk
based
water
Pasteurized
65,
12,
162,
4.41%,
Peaches
Cooked:
NFS
326,
15,
131,
3.31%,
Beef
liver
Fried
54,
11,
209,
2.99%,
Apples
juice/
cider
Uncooked
65,
31,
66,
2.90%,
Peaches
Canned:
NFS
349,
12,
111,
2.69%,
Fish
shellfish
Cooked:
NFS
234,
14,
105,
2.41%,
Beans
succulent
green
Boiled
65,
11,
69,
2.07%,
Peaches
Uncooked
91,
11,
40,
1.98%,
Pineapples
juice
Uncooked
416,
11,
27,
1.57%,
Strawberries
juice
Uncooked
67,
11,
20,
1.42%,
Plums
(damsons)
Uncooked
17,
41,
23,
1.02%,
Strawberries
Frozen:
NFS
Attachment
5
Acute
Dietary
Exposure
Analysis:
Excluding
All
Commodities
with
No
Detects
88
Residue
File
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
Acute
analysis
for
CARBARYL
Residue
file
name:
C:\$
MyFiles\
Carbaryl\
Rdf
files\
sensitivity
no
detects.
RS7
Analysis
Date
04
09
2002
Residue
file
dated:
04
08
2002/
16:
54:
03/
8
Reference
dose
(aRfD)
=
0.01
mg/
kg
bw/
day
RDL
indices
and
parameters
for
Monte
Carlo
Analysis:
Index
Dist
Parameter
#1
Param
#2
Param
#3
Comment
#
Code
1
6
Gardenbeet.
rdf
2
6
Carrot.
rdf
3
6
chic
hors
parsnip
salsify.
rdf
4
6
Potato.
rdf
5
6
radishes.
rdf
6
6
Turnip.
rdf
7
6
sweetpotato.
rdf
8
6
topsgardenbeet.
rdf
9
6
topsradish.
rdf
10
6
Topsturnip.
rdf
11
6
celery.
rdf
12
6
spinach.
rdf
13
6
cannedspinach.
rdf
14
6
lettucehd.
rdf
15
6
lettuceleaf.
rdf
16
6
rhubarb.
rdf
17
6
broccoli.
rdf
18
6
brusselssprouts.
rdf
19
6
cabbage.
rdf
20
6
cauliflower.
rdf
21
6
collards.
rdf
22
6
mustards.
rdf
23
6
kohrabi.
rdf
24
6
beanssucculentfresh.
rdf
25
6
beanssucculentprocessed.
rdf
26
6
beanslima.
rdf
27
6
Peasfresh.
rdf
28
6
Peasprocessed.
rdf
29
6
alleggplant.
rdf
30
6
peppersnonbell.
rdf
31
6
allsweetpepper.
rdf
32
6
tomatoesPB.
rdf
33
6
tomatoesNB.
rdf
34
6
allcucumber.
rdf
35
6
melon.
rdf
36
6
cantaloupe.
rdf
37
6
honeydew.
rdf
38
6
allwatermelon.
rdf
39
6
pumpkin.
rdf
40
6
wintersquash.
rdf
41
6
allsummersquash.
rdf
42
6
citrus.
rdf
43
6
grapefruitjuice.
rdf
44
6
lemonjuice.
rdf
45
6
orangesdecomp.
rdf
46
6
limejuice.
rdf
47
6
orangejuice.
rdf
48
6
appledecomp.
rdf
49
6
apple.
rdf
50
6
applejuice.
rdf
51
6
peardecomp.
rdf
52
6
pear.
rdf
53
6
quince.
rdf
54
6
crabapple.
rdf
55
6
apricot.
rdf
56
6
Apricotss.
rdf
57
6
allsweetcherries.
rdf
58
6
alltartcherries.
rdf
59
6
nectarine.
rdf
60
6
peachSS.
rdf
61
6
Peach.
rdf
62
6
plum2.
rdf
63
6
blackberries.
rdf
64
6
allblueberry.
rdf
Attachment
5
Acute
Dietary
Exposure
Analysis:
Excluding
All
Commodities
with
No
Detects
89
65
6
boysenberry.
rdf
66
6
currant.
rdf
67
6
allraspberries.
rdf
68
6
almonds.
rdf
69
6
chestnut.
rdf
70
6
filbert.
rdf
71
6
pecan.
rdf
72
6
walnut.
rdf
73
6
corn.
rdf
74
6
allasparagus.
rdf
75
6
banana.
rdf
76
6
allcranberry.
rdf
77
6
grapes.
rdf
78
6
grapejuice.
rdf
79
6
okra.
rdf
80
6
olives.
rdf
81
6
pineappledecomp.
rdf
82
6
pineapplemexico.
rdf
83
6
pistachio.
rdf
84
6
strawberrypdp.
rdf
85
6
sunflower.
rdf
86
6
milk2.
rdf
87
6
ruminantliver2.
rdf
88
6
ruminantkidney2.
rdf
89
6
swinemeat2.
rdf
90
6
swinefat2.
rdf
91
6
swineliver2.
rdf
92
6
swinekidney2.
rdf
93
6
poultry.
rdf
94
6
eggs.
rdf
95
6
pineappleother.
rdf
96
6
Plumdecomp.
rdf
97
6
pineappledomestic.
rdf
98
6
appledried.
rdf
99
6
soybean.
rdf
100
6
wheat.
rdf
Food
Crop
Food
Def
Res
Adj.
Factors
RDL
Indices
and
Ratios
Code
Grp
Name
(ppm)
#1
#2
I#
1
Ratio#
1
I#
2
Ratio#
2
I#
3
Ratio#
3
1
13A
Blackberries
1.000000
1.000
1.000
63
1.0000
2
13A
Boysenberries
1.000000
1.000
1.000
65
1.0000
3
13A
Dewberries
1.000000
1.000
1.000
65
1.0000
4
13A
Loganberries
1.000000
1.000
1.000
65
1.0000
5
13A
Raspberries
1.000000
1.000
1.000
67
1.0000
6
13A
Youngberries
1.000000
1.000
1.000
65
1.0000
7
13B
Blueberries
1.000000
1.000
1.000
64
1.0000
8
O
Cranberries
1.000000
1.000
1.000
76
1.0000
9
O
Cranberries
juice
1.000000
1.100
1.000
76
1.0000
10
13B
Currants
1.000000
1.000
1.000
66
1.0000
11
13B
Elderberries
1.000000
1.000
1.000
66
1.0000
12
13B
Gooseberries
1.000000
1.000
1.000
66
1.0000
13
O
Grapes
1.000000
1.000
1.000
77
1.0000
14
O
Grapes
raisins
11
Uncooked
1.000000
2.170
1.000
77
1.0000
12
Cooked:
NFS
1.000000
1.370
1.000
77
1.0000
13
Baked
1.000000
1.370
1.000
77
1.0000
14
Boiled
1.000000
1.370
1.000
77
1.0000
18
Dried
1.000000
1.370
1.000
77
1.0000
42
Frozen:
Cooked
Attachment
5
Acute
Dietary
Exposure
Analysis:
Excluding
All
Commodities
with
No
Detects
90
1.000000
1.370
1.000
77
1.0000
15
O
Grapes
juice
1.000000
1.000
1.000
78
1.0000
16
13B
Huckleberries
1.000000
1.000
1.000
66
1.0000
17
O
Strawberries
1.000000
1.000
1.000
84
1.0000
20
10
Citrus
citron
1.000000
1.000
1.000
42
1.0000
22
10
Grapefruit
peeled
fruit
11
Uncooked
1.000000
1.000
1.000
45
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
45
1.0000
14
Boiled
0.000000
1.000
1.000
31
Canned:
NFS
1.000000
1.000
1.000
42
1.0000
23
10
Grapefruit
juice
1.000000
1.170
1.000
43
1.0000
24
10
Kumquats
1.000000
1.000
1.000
42
1.0000
26
10
Lemons
peeled
fruit
11
Uncooked
1.000000
1.000
1.000
45
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
45
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
42
1.0000
27
10
Lemons
peel
1.000000
1.190
1.000
42
1.0000
28
10
Lemons
juice
1.000000
1.110
1.000
44
1.0000
30
10
Limes
peeled
fruit
1.000000
1.000
1.000
45
1.0000
31
10
Limes
peel
1.000000
1.270
1.000
42
1.0000
32
10
Limes
juice
1.000000
1.110
1.000
46
1.0000
33
10
Oranges
juice
concentrate
1.000000
3.700
1.000
47
1.0000
34
10
Oranges
peeled
fruit
11
Uncooked
1.000000
1.000
1.000
45
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
45
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
42
1.0000
35
10
Oranges
peel
1.000000
1.270
1.000
42
1.0000
36
10
Oranges
juice
1.000000
1.000
1.000
47
1.0000
37
10
Tangelos
1.000000
1.000
1.000
45
1.0000
38
10
Tangerines
11
Uncooked
1.000000
1.000
1.000
45
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
42
1.0000
41
Frozen:
NFS
1.000000
1.000
1.000
42
1.0000
39
10
Tangerines
juice
1.000000
1.280
1.000
46
1.0000
40
14
Almonds
1.000000
1.000
1.000
68
1.0000
43
14
Chestnuts
1.000000
1.000
1.000
69
1.0000
44
14
Filberts
(hazelnuts)
1.000000
1.000
1.000
70
1.0000
48
14
Walnuts
1.000000
1.000
1.000
72
1.0000
50
O
Pistachio
nuts
1.000000
1.000
1.000
83
1.0000
52
11
Apples
11
Uncooked
1.000000
1.000
1.000
48
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
48
1.0000
Attachment
5
Acute
Dietary
Exposure
Analysis:
Excluding
All
Commodities
with
No
Detects
91
13
Baked
1.000000
1.000
1.000
48
1.0000
14
Boiled
1.000000
1.000
1.000
48
1.0000
15
Fried
1.000000
1.000
1.000
48
1.0000
18
Dried
0.009000
1.000
1.000
98
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
49
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
49
1.0000
33
Canned:
Baked
1.000000
1.000
1.000
49
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
49
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
49
1.0000
53
11
Apples
dried
1.000000
2.600
1.000
49
1.0000
54
11
Apples
juice/
cider
1.000000
1.000
1.000
50
1.0000
55
11
Crabapples
1.000000
1.000
1.000
54
1.0000
56
11
Pears
11
Uncooked
1.000000
1.000
1.000
51
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
51
1.0000
13
Baked
1.000000
1.000
1.000
51
1.0000
14
Boiled
1.000000
1.000
1.000
51
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
52
1.0000
57
11
Pears
dried
1.000000
2.600
1.000
52
1.0000
58
11
Quinces
1.000000
1.000
1.000
53
1.0000
59
12
Apricots
11
Uncooked
1.000000
1.000
1.000
56
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
56
1.0000
14
Boiled
1.000000
1.000
1.000
56
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
55
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
55
1.0000
60
12
Apricots
dried
1.000000
6.000
1.000
55
1.0000
61
12
Cherries
11
Uncooked
1.000000
1.000
1.000
57
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
58
1.0000
13
Baked
1.000000
1.000
1.000
58
1.0000
14
Boiled
1.000000
1.000
1.000
58
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
58
1.0000
33
Canned:
Baked
1.000000
1.000
1.000
58
1.0000
41
Frozen:
NFS
1.000000
1.000
1.000
58
1.0000
62
12
Cherries
dried
1.000000
4.000
1.000
57
1.0000
63
12
Cherries
juice
1.000000
1.500
1.000
58
1.0000
64
12
Nectarines
1.000000
1.000
1.000
59
1.0000
65
12
Peaches
11
Uncooked
1.000000
1.000
1.000
60
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
60
1.0000
Attachment
5
Acute
Dietary
Exposure
Analysis:
Excluding
All
Commodities
with
No
Detects
92
13
Baked
1.000000
1.000
1.000
60
1.0000
14
Boiled
1.000000
1.000
1.000
60
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
61
1.0000
41
Frozen:
NFS
1.000000
1.000
1.000
61
1.0000
66
12
Peaches
dried
1.000000
7.000
1.000
61
1.0000
67
12
Plums
(damsons)
11
Uncooked
1.000000
1.000
1.000
96
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
96
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
62
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
62
1.0000
51
Cured:
NFS
(smoked/
p
1.000000
1.000
1.000
62
1.0000
68
12
Plums
prunes
(dried)
1.000000
0.150
1.000
62
1.0000
69
12
Plums/
prune
juice
1.000000
1.400
1.000
62
1.0000
81
11
Loquats
1.000000
1.000
1.000
53
1.0000
82
O
Olives
1.000000
1.000
1.000
80
1.0000
89
O
Pineapples
peeled
fruit
11
Uncooked
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
12
Cooked:
NFS
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
13
Baked
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
14
Boiled
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
31
Canned:
NFS
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
33
Canned:
Baked
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
41
Frozen:
NFS
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
90
O
Pineapples
dried
1.000000
5.000
1.000
82
0.0250
95
0.4750
97
0.5000
91
O
Pineapples
juice
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
123
19A
Dill
0.004000
1.000
1.000
139
8
Paprika
1.000000
1.000
1.000
30
1.0000
141
9A
Melons
cantaloupes
juice
1.000000
1.000
1.000
36
1.0000
142
9A
Melons
cantaloupes
pulp
1.000000
1.000
1.000
36
1.0000
143
9A
Casabas
1.000000
1.000
1.000
35
1.0000
144
9A
Crenshaws
1.000000
1.000
1.000
35
1.0000
145
9A
Melons
honeydew
1.000000
1.000
1.000
37
1.0000
146
9A
Melons
persian
1.000000
1.000
1.000
35
1.0000
147
9A
Watermelon
1.000000
1.000
1.000
38
1.0000
148
9B
Cucumbers
1.000000
1.000
1.000
34
1.0000
149
9B
Pumpkin
1.000000
1.000
1.000
39
1.0000
150
9B
Squash
summer
1.000000
1.000
1.000
41
1.0000
151
9B
Squash
winter
1.000000
1.000
1.000
40
1.0000
152
9B
Bitter
melon
1.000000
1.000
1.000
35
1.0000
154
8
Eggplant
1.000000
1.000
1.000
29
1.0000
Attachment
5
Acute
Dietary
Exposure
Analysis:
Excluding
All
Commodities
with
No
Detects
93
155
8
Peppers
sweet(
garden)
1.000000
1.000
1.000
31
1.0000
156
8
Peppers
chilli
incl
jalapeno
1.000000
1.000
1.000
30
1.0000
157
8
Peppers
other
1.000000
1.000
1.000
30
1.0000
158
8
Pimientos
1.000000
1.000
1.000
30
1.0000
159
8
Tomatoes
whole
11
Uncooked
1.000000
1.000
1.000
33
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
33
1.0000
13
Baked
1.000000
1.000
1.000
33
1.0000
14
Boiled
1.000000
1.000
1.000
33
1.0000
15
Fried
1.000000
1.000
1.000
33
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
32
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
32
1.0000
33
Canned:
Baked
1.000000
1.000
1.000
32
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
32
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
32
1.0000
160
8
Tomatoes
juice
1.000000
0.540
1.000
32
1.0000
161
8
Tomatoes
puree
1.000000
0.650
1.000
32
1.0000
162
8
Tomatoes
paste
1.000000
0.650
1.000
32
1.0000
163
8
Tomatoes
catsup
1.000000
0.650
1.000
32
1.0000
165
2
Beets
garden
tops(
greens)
1.000000
1.000
1.000
8
1.0000
168
5A
Broccoli
1.000000
1.000
1.000
17
1.0000
171
5A
Cauliflower
1.000000
1.000
1.000
20
1.0000
172
5B
Collards
1.000000
1.000
1.000
21
1.0000
174
5B
Kale
1.000000
1.000
1.000
22
1.0000
177
4A
Dandelion
greens
1.000000
1.000
1.000
12
1.0000
178
4A
Endive
curley
and
escarole
1.000000
1.000
1.000
15
1.0000
183
5B
Mustard
greens
1.000000
1.000
1.000
22
1.0000
184
4A
Parsley
1.000000
1.000
1.000
12
1.0000
186
4A
Spinach
11
Uncooked
1.000000
1.000
1.000
12
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
12
1.0000
13
Baked
0.000000
1.000
1.000
14
Boiled
1.000000
1.000
1.000
12
1.0000
31
Canned:
NFS
0.000000
1.000
1.000
32
Canned:
Cooked
0.000000
1.000
1.000
34
Canned:
Boiled
0.000000
1.000
1.000
42
Frozen:
Cooked
1.000000
1.000
1.000
12
1.0000
44
Frozen:
Boiled
1.000000
1.000
1.000
12
1.0000
188
2
Turnips
tops
1.000000
1.000
1.000
10
1.0000
195
O
Grapes
leaves
1.000000
1.000
1.000
77
1.0000
Attachment
5
Acute
Dietary
Exposure
Analysis:
Excluding
All
Commodities
with
No
Detects
94
197
1AB
Beets
garden
roots
1.000000
1.000
1.000
1
1.0000
212
1AB
Radishes
roots
1.000000
1.000
1.000
5
1.0000
213
2
Radishes
tops
1.000000
1.000
1.000
9
1.0000
214
1AB
Rutabagas
roots
1.000000
1.000
1.000
6
1.0000
215
2
Rutabagas
tops
1.000000
1.000
1.000
10
1.0000
218
1CD
Sweet
potatoes
(incl
yams)
1.000000
1.000
1.000
7
1.0000
219
1AB
Turnips
roots
1.000000
1.000
1.000
6
1.0000
227
6C
Beans
dry
great
northern
0.002000
1.000
1.000
228
6C
Beans
dry
kidney
0.002000
1.000
1.000
229
6C
Beans
dry
lima
0.002000
1.000
1.000
230
6C
Beans
dry
navy
(pea)
0.002000
1.000
1.000
231
6C
Beans
dry
other
0.002000
1.000
1.000
232
6C
Beans
dry
pinto
0.002000
1.000
1.000
233
6B
Beans
succulent
lima
1.000000
1.000
1.000
26
1.0000
234
6A
Beans
succulent
green
11
Uncooked
1.000000
1.000
1.000
24
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
24
1.0000
14
Boiled
1.000000
1.000
1.000
24
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
25
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
25
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
25
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
25
1.0000
44
Frozen:
Boiled
1.000000
1.000
1.000
25
1.0000
51
Cured:
NFS
(smoked/
p
1.000000
1.000
1.000
25
1.0000
235
6A
Beans
succulent
other
1.000000
1.000
1.000
25
1.0000
236
6A
Beans
succulent
yellow/
wax
14
Boiled
1.000000
1.000
1.000
24
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
25
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
25
1.0000
240
6C
Peas
(garden)
dry
0.013000
0.045
1.000
241
6AB
Peas
(garden)
green
11
Uncooked
1.000000
1.000
1.000
27
1.0000
12
Cooked:
NFS
1.000000
0.150
1.000
27
1.0000
13
Baked
1.000000
0.150
1.000
27
1.0000
14
Boiled
1.000000
0.150
1.000
27
1.0000
15
Fried
1.000000
0.150
1.000
27
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
28
1.0000
32
Canned:
Cooked
1.000000
0.150
1.000
28
1.0000
34
Canned:
Boiled
1.000000
0.150
1.000
28
1.0000
42
Frozen:
Cooked
1.000000
0.150
1.000
28
1.0000
44
Frozen:
Boiled
Attachment
5
Acute
Dietary
Exposure
Analysis:
Excluding
All
Commodities
with
No
Detects
95
1.000000
0.150
1.000
28
1.0000
45
Frozen:
Fried
1.000000
0.150
1.000
28
1.0000
243
6C
Lentils
0.002000
1.000
1.000
244
6C
Mung
beans
(sprouts)
0.002000
1.000
1.000
245
O
Okra
12
Cooked:
NFS
1.000000
0.180
1.000
79
1.0000
14
Boiled
1.000000
0.050
1.000
79
1.0000
15
Fried
1.000000
0.180
1.000
79
1.0000
32
Canned:
Cooked
1.000000
0.180
1.000
79
1.0000
42
Frozen:
Cooked
1.000000
0.180
1.000
79
1.0000
44
Frozen:
Boiled
1.000000
0.050
1.000
79
1.0000
249
6C
Beans
dry
broadbeans
0.002000
1.000
1.000
250
6B
Beans
succulent
broadbeans
1.000000
1.000
1.000
24
1.0000
251
6C
Beans
dry
pigeon
beans
0.002000
1.000
1.000
253
6
Beans
unspecified
1.000000
1.000
1.000
24
1.0000
256
O
Beans
dry
hyacinth
0.002000
1.000
1.000
257
O
Beans
succulent
hyacinth
1.000000
1.000
1.000
24
1.0000
258
6C
Beans
dry
blackeye
peas/
cowpea
0.002000
1.000
1.000
259
6C
Beans
dry
garbanzo/
chick
pea
0.002000
1.000
1.000
260
O
Asparagus
1.000000
1.000
1.000
74
1.0000
270
15
Rice
rough
(brown)
0.074000
1.000
1.000
271
15
Rice
milled
(white)
0.074000
0.030
1.000
275
15
Sorghum
(including
milo)
0.000015
1.000
1.000
100
1.0000
276
15
Wheat
rough
0.000015
1.000
1.000
100
1.0000
277
15
Wheat
germ
0.000015
1.000
1.000
278
15
Wheat
bran
0.000015
1.000
1.000
279
15
Wheat
flour
0.000015
1.000
1.000
280
15
Millet
0.000015
1.000
1.000
100
1.0000
287
6C
Guar
beans
1.000000
1.000
1.000
24
1.0000
298
O
Sunflower
oil
0.000400
0.670
1.000
300
O
Olive
oil
0.077000
0.810
1.000
315
O
Grapes
wine
and
sherry
1.000000
1.000
1.000
77
1.0000
321
M
Beef
meat
byproducts
3.675000
1.000
1.000
88
1.0000
322
M
Beef
other
organ
meats
3.675000
1.000
1.000
88
1.0000
325
M
Beef
kidney
3.675000
1.000
1.000
88
1.0000
326
M
Beef
liver
1.390000
1.000
1.000
87
1.0000
328
M
Goat
meat
byproducts
3.675000
1.000
1.000
88
1.0000
329
M
Goat
other
organ
meats
3.675000
1.000
1.000
88
1.0000
331
M
Goat
kidney
3.675000
1.000
1.000
88
1.0000
332
M
Goat
liver
1.390000
1.000
1.000
87
1.0000
Attachment
5
Acute
Dietary
Exposure
Analysis:
Excluding
All
Commodities
with
No
Detects
96
336
M
Sheep
meat
byproducts
3.675000
1.000
1.000
88
1.0000
337
M
Sheep
other
organ
meats
3.675000
1.000
1.000
88
1.0000
339
M
Sheep
kidney
3.675000
1.000
1.000
88
1.0000
340
M
Sheep
liver
1.390000
1.000
1.000
87
1.0000
342
M
Pork
meat
byproducts
0.260000
1.000
1.000
92
1.0000
343
M
Pork
other
organ
meats
0.260000
1.000
1.000
92
1.0000
345
M
Pork
kidney
0.260000
1.000
1.000
92
1.0000
346
M
Pork
liver
0.100000
1.000
1.000
91
1.0000
349
F
Fish
shellfish
0.250000
1.000
1.000
377
11
Apples
juice
concentrate
1.000000
3.000
1.000
50
1.0000
380
13A
Blackberries
juice
1.000000
1.000
1.000
63
1.0000
389
O
Cranberries
juice
concentrate
1.000000
3.300
1.000
76
1.0000
392
O
Grapes
juice
concentrate
1.000000
3.000
1.000
78
1.0000
402
12
Peaches
juice
1.000000
1.000
1.000
61
1.0000
404
11
Pears
juice
1.000000
0.370
1.000
52
1.0000
405
6B
Peas
succulent/
blackeye/
cowpea
12
Cooked:
NFS
1.000000
0.150
1.000
27
1.0000
14
Boiled
1.000000
0.150
1.000
27
1.0000
32
Canned:
Cooked
1.000000
0.150
1.000
28
1.0000
42
Frozen:
Cooked
1.000000
0.150
1.000
28
1.0000
406
O
Pineapples
juice
concentrate
1.000000
2.000
1.000
82
0.0250
95
0.4750
97
0.5000
407
1AB
Radishes
japanese
(daiken)
1.000000
1.000
1.000
5
1.0000
408
15
Rice
bran
0.074000
0.400
1.000
410
12
Apricot
juice
1.000000
1.000
1.000
55
1.0000
413
6A
Snowpeas
11
Uncooked
1.000000
1.000
1.000
27
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
27
1.0000
14
Boiled
1.000000
1.000
1.000
27
1.0000
15
Fried
1.000000
1.000
1.000
27
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
28
1.0000
415
9B
Squash
spaghetti
1.000000
1.000
1.000
40
1.0000
416
O
Strawberries
juice
1.000000
1.000
1.000
84
1.0000
417
O
Sunflower
seeds
1.000000
1.000
1.000
85
1.0000
420
10
Tangerines
juice
concentrate
1.000000
4.080
1.000
46
1.0000
423
8
Tomatoes
dried
1.000000
0.520
1.000
32
1.0000
426
M
Veal
kidney
3.675000
1.000
1.000
88
1.0000
427
M
Veal
liver
1.390000
1.000
1.000
87
1.0000
428
M
Veal
other
organ
meats
3.675000
1.000
1.000
88
1.0000
430
M
Veal
meat
byproducts
3.675000
1.000
1.000
88
1.0000
431
14
Walnut
oil
0.005400
1.000
1.000
Attachment
5
Acute
Dietary
Exposure
Analysis:
Excluding
All
Commodities
with
No
Detects
97
436
9A
Watermelon
juice
1.000000
1.000
1.000
38
1.0000
437
15
Wheat
germ
oil
0.000015
1.000
1.000
439
9B
Wintermelon
1.000000
1.000
1.000
35
1.0000
441
10
Grapefruit
juice
concentrate
1.000000
4.580
1.000
43
1.0000
442
10
Lemons
juice
concentrate
1.000000
6.330
1.000
44
1.0000
443
10
Limes
juice
concentrate
1.000000
3.330
1.000
46
1.0000
448
10
Grapefruit
peel
1.000000
1.000
1.000
42
1.0000
Attachment
5
Acute
Dietary
Exposure
Analysis:
Excluding
All
Commodities
with
No
Detects
98
Results
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
ACUTE
Analysis
for
CARBARYL
(1989
92
data)
Residue
file:
sensitivity
no
detects.
RS7
Adjustment
factor
#2
NOT
used.
Analysis
Date:
04
08
2002/
17:
16:
12
Residue
file
dated:
04
08
2002/
16:
54:
03/
8
Daily
totals
for
food
and
foodform
consumption
used.
MC
iterations
=
1000
MC
list
in
residue
file
MC
seed
=
10
Run
Comment:
""
===============================================================================
Summary
calculations
(per
capita):
95th
Percentile
99th
Percentile
99.9th
Percentile
Exposure
%
aRfD
Exposure
%
aRfD
Exposure
%
aRfD
U.
S.
Population:
0.000230
2.30
0.001012
10.12
0.005870
58.70
All
infants:
0.000440
4.40
0.002610
26.10
0.012965
129.65
Nursing
infants
(<
1
yr
old):
0.000097
0.97
0.001223
12.23
0.008363
83.63
Non
nursing
infants
(<
1
yr
old):
0.000574
5.74
0.003120
31.20
0.013802
138.02
Children
1
6
yrs:
0.000473
4.73
0.001967
19.67
0.010765
107.65
Children
7
12
yrs:
0.000279
2.79
0.001400
14.00
0.008555
85.55
Females
13+
(preg/
not
nursing):
0.000191
1.91
0.000882
8.82
0.005836
58.36
Females
13+
(nursing):
0.000247
2.47
0.001371
13.71
0.007050
70.50
Females
13
19
(not
preg
or
nursing):
0.000107
1.07
0.000660
6.60
0.004499
44.99
Females
20+
(not
preg
or
nursing):
0.000197
1.97
0.000943
9.43
0.004810
48.10
Females
13
50
yrs:
0.000184
1.84
0.000877
8.77
0.004434
44.34
Males
13
19
yrs:
0.000138
1.38
0.000721
7.21
0.003802
38.02
Males
20+
yrs:
0.000214
2.14
0.000863
8.63
0.004178
41.78
Seniors
55+:
0.000207
2.07
0.001008
10.08
0.005703
57.03
Attachment
6
Acute
Dietary
Exposure
Analysis
:
Excluding
Peaches
99
Residue
File
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
Acute
analysis
for
CARBARYL
Residue
file
name:
C:\$
MyFiles\
Carbaryl\
Rdf
files\$$$
10carbarylfinal9
no
peaches.
RS7
Analysis
Date
04
15
2002
Residue
file
dated:
04
03
2002/
14:
28:
13/
8
Reference
dose
(aRfD)
=
0.01
mg/
kg
bw/
day
RDL
indices
and
parameters
for
Monte
Carlo
Analysis:
Index
Dist
Parameter
#1
Param
#2
Param
#3
Comment
#
Code
1
6
Gardenbeet.
rdf
2
6
Carrot.
rdf
3
6
chic
hors
parsnip
salsify.
rdf
4
6
Potato.
rdf
5
6
radishes.
rdf
6
6
Turnip.
rdf
7
6
sweetpotato.
rdf
8
6
topsgardenbeet.
rdf
9
6
topsradish.
rdf
10
6
Topsturnip.
rdf
11
6
celery.
rdf
12
6
spinach.
rdf
13
6
cannedspinach.
rdf
14
6
lettucehd.
rdf
15
6
lettuceleaf.
rdf
16
6
rhubarb.
rdf
17
6
broccoli.
rdf
18
6
brusselssprouts.
rdf
19
6
cabbage.
rdf
20
6
cauliflower.
rdf
21
6
collards.
rdf
22
6
mustards.
rdf
23
6
kohrabi.
rdf
24
6
beanssucculentfresh.
rdf
25
6
beanssucculentprocessed.
rdf
26
6
beanslima.
rdf
27
6
Peasfresh.
rdf
28
6
Peasprocessed.
rdf
29
6
alleggplant.
rdf
30
6
peppersnonbell.
rdf
31
6
allsweetpepper.
rdf
32
6
tomatoesPB.
rdf
33
6
tomatoesNB.
rdf
34
6
allcucumber.
rdf
35
6
melon.
rdf
36
6
cantaloupe.
rdf
37
6
honeydew.
rdf
38
6
allwatermelon.
rdf
39
6
pumpkin.
rdf
40
6
wintersquash.
rdf
41
6
allsummersquash.
rdf
42
6
citrus.
rdf
43
6
grapefruitjuice.
rdf
44
6
lemonjuice.
rdf
45
6
orangesdecomp.
rdf
46
6
limejuice.
rdf
47
6
orangejuice.
rdf
48
6
appledecomp.
rdf
49
6
apple.
rdf
50
6
applejuice.
rdf
51
6
peardecomp.
rdf
52
6
pear.
rdf
53
6
quince.
rdf
54
6
crabapple.
rdf
55
6
apricot.
rdf
56
6
Apricotss.
rdf
57
6
allsweetcherries.
rdf
58
6
alltartcherries.
rdf
59
6
nectarine.
rdf
60
6
peachSS.
rdf
61
6
Peach.
rdf
62
6
plum2.
rdf
63
6
blackberries.
rdf
64
6
allblueberry.
rdf
65
6
boysenberry.
rdf
Attachment
6
Acute
Dietary
Exposure
Analysis
:
Excluding
Peaches
100
66
6
currant.
rdf
67
6
allraspberries.
rdf
68
6
almonds.
rdf
69
6
chestnut.
rdf
70
6
filbert.
rdf
71
6
pecan.
rdf
72
6
walnut.
rdf
73
6
corn.
rdf
74
6
allasparagus.
rdf
75
6
banana.
rdf
76
6
allcranberry.
rdf
77
6
grapes.
rdf
78
6
grapejuice.
rdf
79
6
okra.
rdf
80
6
olives.
rdf
81
6
pineappledecomp.
rdf
82
6
pineapplemexico.
rdf
83
6
pistachio.
rdf
84
6
strawberrypdp.
rdf
85
6
sunflower.
rdf
86
6
milk2.
rdf
87
6
ruminantliver2.
rdf
88
6
ruminantkidney2.
rdf
89
6
swinemeat2.
rdf
90
6
swinefat2.
rdf
91
6
swineliver2.
rdf
92
6
swinekidney2.
rdf
93
6
poultry.
rdf
94
6
eggs.
rdf
95
6
pineappleother.
rdf
96
6
Plumdecomp.
rdf
97
6
pineappledomestic.
rdf
98
6
appledried.
rdf
99
6
soybean.
rdf
100
6
wheat.
rdf
Food
Crop
Food
Def
Res
Adj.
Factors
RDL
Indices
and
Ratios
Code
Grp
Name
(ppm)
#1
#2
I#
1
Ratio#
1
I#
2
Ratio#
2
I#
3
Ratio#
3
1
13A
Blackberries
1.000000
1.000
1.000
63
1.0000
2
13A
Boysenberries
1.000000
1.000
1.000
65
1.0000
3
13A
Dewberries
1.000000
1.000
1.000
65
1.0000
4
13A
Loganberries
1.000000
1.000
1.000
65
1.0000
5
13A
Raspberries
1.000000
1.000
1.000
67
1.0000
6
13A
Youngberries
1.000000
1.000
1.000
65
1.0000
7
13B
Blueberries
1.000000
1.000
1.000
64
1.0000
8
O
Cranberries
1.000000
1.000
1.000
76
1.0000
9
O
Cranberries
juice
1.000000
1.100
1.000
76
1.0000
10
13B
Currants
1.000000
1.000
1.000
66
1.0000
11
13B
Elderberries
1.000000
1.000
1.000
66
1.0000
12
13B
Gooseberries
1.000000
1.000
1.000
66
1.0000
13
O
Grapes
1.000000
1.000
1.000
77
1.0000
14
O
Grapes
raisins
11
Uncooked
1.000000
2.170
1.000
77
1.0000
12
Cooked:
NFS
1.000000
1.370
1.000
77
1.0000
13
Baked
1.000000
1.370
1.000
77
1.0000
14
Boiled
1.000000
1.370
1.000
77
1.0000
18
Dried
1.000000
1.370
1.000
77
1.0000
42
Frozen:
Cooked
1.000000
1.370
1.000
77
1.0000
Attachment
6
Acute
Dietary
Exposure
Analysis
:
Excluding
Peaches
101
15
O
Grapes
juice
1.000000
1.000
1.000
78
1.0000
16
13B
Huckleberries
1.000000
1.000
1.000
66
1.0000
17
O
Strawberries
1.000000
1.000
1.000
84
1.0000
20
10
Citrus
citron
1.000000
1.000
1.000
42
1.0000
22
10
Grapefruit
peeled
fruit
11
Uncooked
1.000000
1.000
1.000
45
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
45
1.0000
14
Boiled
0.000000
1.000
1.000
31
Canned:
NFS
1.000000
1.000
1.000
42
1.0000
23
10
Grapefruit
juice
1.000000
1.170
1.000
43
1.0000
24
10
Kumquats
1.000000
1.000
1.000
42
1.0000
26
10
Lemons
peeled
fruit
11
Uncooked
1.000000
1.000
1.000
45
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
45
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
42
1.0000
27
10
Lemons
peel
1.000000
1.190
1.000
42
1.0000
28
10
Lemons
juice
1.000000
1.110
1.000
44
1.0000
30
10
Limes
peeled
fruit
1.000000
1.000
1.000
45
1.0000
31
10
Limes
peel
1.000000
1.270
1.000
42
1.0000
32
10
Limes
juice
1.000000
1.110
1.000
46
1.0000
33
10
Oranges
juice
concentrate
1.000000
3.700
1.000
47
1.0000
34
10
Oranges
peeled
fruit
11
Uncooked
1.000000
1.000
1.000
45
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
45
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
42
1.0000
35
10
Oranges
peel
1.000000
1.270
1.000
42
1.0000
36
10
Oranges
juice
1.000000
1.000
1.000
47
1.0000
37
10
Tangelos
1.000000
1.000
1.000
45
1.0000
38
10
Tangerines
11
Uncooked
1.000000
1.000
1.000
45
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
42
1.0000
41
Frozen:
NFS
1.000000
1.000
1.000
42
1.0000
39
10
Tangerines
juice
1.000000
1.280
1.000
46
1.0000
40
14
Almonds
1.000000
1.000
1.000
68
1.0000
43
14
Chestnuts
1.000000
1.000
1.000
69
1.0000
44
14
Filberts
(hazelnuts)
1.000000
1.000
1.000
70
1.0000
48
14
Walnuts
1.000000
1.000
1.000
72
1.0000
50
O
Pistachio
nuts
1.000000
1.000
1.000
83
1.0000
52
11
Apples
11
Uncooked
1.000000
1.000
1.000
48
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
48
1.0000
13
Baked
Attachment
6
Acute
Dietary
Exposure
Analysis
:
Excluding
Peaches
102
1.000000
1.000
1.000
48
1.0000
14
Boiled
1.000000
1.000
1.000
48
1.0000
15
Fried
1.000000
1.000
1.000
48
1.0000
18
Dried
0.009000
1.000
1.000
98
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
49
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
49
1.0000
33
Canned:
Baked
1.000000
1.000
1.000
49
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
49
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
49
1.0000
53
11
Apples
dried
1.000000
2.600
1.000
49
1.0000
54
11
Apples
juice/
cider
1.000000
1.000
1.000
50
1.0000
55
11
Crabapples
1.000000
1.000
1.000
54
1.0000
56
11
Pears
11
Uncooked
1.000000
1.000
1.000
51
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
51
1.0000
13
Baked
1.000000
1.000
1.000
51
1.0000
14
Boiled
1.000000
1.000
1.000
51
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
52
1.0000
57
11
Pears
dried
1.000000
2.600
1.000
52
1.0000
58
11
Quinces
1.000000
1.000
1.000
53
1.0000
59
12
Apricots
11
Uncooked
1.000000
1.000
1.000
56
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
56
1.0000
14
Boiled
1.000000
1.000
1.000
56
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
55
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
55
1.0000
60
12
Apricots
dried
1.000000
6.000
1.000
55
1.0000
61
12
Cherries
11
Uncooked
1.000000
1.000
1.000
57
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
58
1.0000
13
Baked
1.000000
1.000
1.000
58
1.0000
14
Boiled
1.000000
1.000
1.000
58
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
58
1.0000
33
Canned:
Baked
1.000000
1.000
1.000
58
1.0000
41
Frozen:
NFS
1.000000
1.000
1.000
58
1.0000
62
12
Cherries
dried
1.000000
4.000
1.000
57
1.0000
63
12
Cherries
juice
1.000000
1.500
1.000
58
1.0000
64
12
Nectarines
1.000000
1.000
1.000
59
1.0000
67
12
Plums
(damsons)
11
Uncooked
1.000000
1.000
1.000
96
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
96
1.0000
31
Canned:
NFS
Attachment
6
Acute
Dietary
Exposure
Analysis
:
Excluding
Peaches
103
1.000000
1.000
1.000
62
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
62
1.0000
51
Cured:
NFS
(smoked/
p
1.000000
1.000
1.000
62
1.0000
68
12
Plums
prunes
(dried)
1.000000
0.150
1.000
62
1.0000
69
12
Plums/
prune
juice
1.000000
1.400
1.000
62
1.0000
72
O
Bananas
1.000000
1.000
1.000
75
1.0000
73
O
Bananas
dried
1.000000
3.900
1.000
75
1.0000
81
11
Loquats
1.000000
1.000
1.000
53
1.0000
82
O
Olives
1.000000
1.000
1.000
80
1.0000
89
O
Pineapples
peeled
fruit
11
Uncooked
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
12
Cooked:
NFS
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
13
Baked
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
14
Boiled
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
31
Canned:
NFS
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
33
Canned:
Baked
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
41
Frozen:
NFS
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
90
O
Pineapples
dried
1.000000
5.000
1.000
82
0.0250
95
0.4750
97
0.5000
91
O
Pineapples
juice
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
94
O
Plantains
ripe
1.000000
1.000
1.000
75
1.0000
123
19A
Dill
0.004000
1.000
1.000
126
1AB
Horseradish
1.000000
1.000
1.000
3
1.0000
139
8
Paprika
1.000000
1.000
1.000
30
1.0000
141
9A
Melons
cantaloupes
juice
1.000000
1.000
1.000
36
1.0000
142
9A
Melons
cantaloupes
pulp
1.000000
1.000
1.000
36
1.0000
143
9A
Casabas
1.000000
1.000
1.000
35
1.0000
144
9A
Crenshaws
1.000000
1.000
1.000
35
1.0000
145
9A
Melons
honeydew
1.000000
1.000
1.000
37
1.0000
146
9A
Melons
persian
1.000000
1.000
1.000
35
1.0000
147
9A
Watermelon
1.000000
1.000
1.000
38
1.0000
148
9B
Cucumbers
1.000000
1.000
1.000
34
1.0000
149
9B
Pumpkin
1.000000
1.000
1.000
39
1.0000
150
9B
Squash
summer
1.000000
1.000
1.000
41
1.0000
151
9B
Squash
winter
1.000000
1.000
1.000
40
1.0000
152
9B
Bitter
melon
1.000000
1.000
1.000
35
1.0000
154
8
Eggplant
1.000000
1.000
1.000
29
1.0000
155
8
Peppers
sweet(
garden)
1.000000
1.000
1.000
31
1.0000
156
8
Peppers
chilli
incl
jalapeno
1.000000
1.000
1.000
30
1.0000
157
8
Peppers
other
1.000000
1.000
1.000
30
1.0000
158
8
Pimientos
1.000000
1.000
1.000
30
1.0000
Attachment
6
Acute
Dietary
Exposure
Analysis
:
Excluding
Peaches
104
159
8
Tomatoes
whole
11
Uncooked
1.000000
1.000
1.000
33
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
33
1.0000
13
Baked
1.000000
1.000
1.000
33
1.0000
14
Boiled
1.000000
1.000
1.000
33
1.0000
15
Fried
1.000000
1.000
1.000
33
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
32
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
32
1.0000
33
Canned:
Baked
1.000000
1.000
1.000
32
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
32
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
32
1.0000
160
8
Tomatoes
juice
1.000000
0.540
1.000
32
1.0000
161
8
Tomatoes
puree
1.000000
0.650
1.000
32
1.0000
162
8
Tomatoes
paste
1.000000
0.650
1.000
32
1.0000
163
8
Tomatoes
catsup
1.000000
0.650
1.000
32
1.0000
165
2
Beets
garden
tops(
greens)
1.000000
1.000
1.000
8
1.0000
166
4B
Celery
1.000000
1.000
1.000
11
1.0000
168
5A
Broccoli
1.000000
1.000
1.000
17
1.0000
169
5A
Brussels
sprouts
1.000000
1.000
1.000
18
1.0000
170
5A
Cabbage
green
and
red
11
Uncooked
1.000000
0.250
1.000
19
1.0000
12
Cooked:
NFS
1.000000
0.025
1.000
19
1.0000
13
Baked
1.000000
0.025
1.000
19
1.0000
14
Boiled
1.000000
0.025
1.000
19
1.0000
15
Fried
1.000000
0.025
1.000
19
1.0000
31
Canned:
NFS
1.000000
0.250
1.000
19
1.0000
32
Canned:
Cooked
1.000000
0.025
1.000
19
1.0000
51
Cured:
NFS
(smoked/
p
1.000000
0.025
1.000
19
1.0000
171
5A
Cauliflower
1.000000
1.000
1.000
20
1.0000
172
5B
Collards
1.000000
1.000
1.000
21
1.0000
174
5B
Kale
1.000000
1.000
1.000
22
1.0000
175
5A
Kohlrabi
1.000000
1.000
1.000
23
1.0000
176
4A
Lettuce
leafy
varieties
1.000000
1.000
1.000
15
1.0000
177
4A
Dandelion
greens
1.000000
1.000
1.000
12
1.0000
178
4A
Endive
curley
and
escarole
1.000000
1.000
1.000
15
1.0000
182
4A
Lettuce
unspecified
1.000000
1.000
1.000
14
1.0000
183
5B
Mustard
greens
1.000000
1.000
1.000
22
1.0000
184
4A
Parsley
1.000000
1.000
1.000
12
1.0000
185
4B
Rhubarb
1.000000
1.000
1.000
16
1.0000
186
4A
Spinach
11
Uncooked
Attachment
6
Acute
Dietary
Exposure
Analysis
:
Excluding
Peaches
105
1.000000
1.000
1.000
12
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
12
1.0000
13
Baked
0.000000
1.000
1.000
14
Boiled
1.000000
1.000
1.000
12
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
13
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
13
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
13
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
12
1.0000
44
Frozen:
Boiled
1.000000
1.000
1.000
12
1.0000
187
4B
Swiss
chard
1.000000
1.000
1.000
16
1.0000
188
2
Turnips
tops
1.000000
1.000
1.000
10
1.0000
192
4A
Lettuce
head
varieties
1.000000
1.000
1.000
14
1.0000
195
O
Grapes
leaves
1.000000
1.000
1.000
77
1.0000
197
1AB
Beets
garden
roots
1.000000
1.000
1.000
1
1.0000
198
1AB
Carrots
1.000000
1.000
1.000
2
1.0000
207
1C
Potatoes/
white
whole
11
Uncooked
1.000000
1.000
1.000
4
1.0000
12
Cooked:
NFS
1.000000
0.040
1.000
4
1.0000
13
Baked
1.000000
1.200
1.000
4
1.0000
14
Boiled
1.000000
2.500
1.000
4
1.0000
15
Fried
1.000000
0.040
1.000
4
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
4
1.0000
208
1C
Potatoes/
white
unspecified
1.000000
1.000
1.000
4
1.0000
209
1C
Potatoes/
white
peeled
11
Uncooked
0.000000
1.000
1.000
12
Cooked:
NFS
1.000000
1.000
1.000
4
1.0000
13
Baked
1.000000
1.200
1.000
4
1.0000
14
Boiled
1.000000
2.500
1.000
4
1.0000
15
Fried
1.000000
0.040
1.000
4
1.0000
31
Canned:
NFS
0.000000
1.000
1.000
32
Canned:
Cooked
1.000000
1.000
1.000
4
1.0000
34
Canned:
Boiled
1.000000
2.500
1.000
4
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
4
1.0000
43
Frozen:
Baked
1.000000
1.200
1.000
4
1.0000
45
Frozen:
Fried
1.000000
0.040
1.000
4
1.0000
210
1C
Potatoes/
white
dry
0.000357
0.020
1.000
211
1C
Potatoes/
white
peel
only
13
Baked
1.000000
1.200
1.000
4
1.0000
15
Fried
1.000000
0.040
1.000
4
1.0000
212
1AB
Radishes
roots
1.000000
1.000
1.000
5
1.0000
213
2
Radishes
tops
1.000000
1.000
1.000
9
1.0000
Attachment
6
Acute
Dietary
Exposure
Analysis
:
Excluding
Peaches
106
214
1AB
Rutabagas
roots
1.000000
1.000
1.000
6
1.0000
215
2
Rutabagas
tops
1.000000
1.000
1.000
10
1.0000
216
1AB
Salsify(
oyster
plant)
1.000000
1.000
1.000
3
1.0000
218
1CD
Sweet
potatoes
(incl
yams)
1.000000
1.000
1.000
7
1.0000
219
1AB
Turnips
roots
1.000000
1.000
1.000
6
1.0000
220
1AB
Parsnips
1.000000
1.000
1.000
3
1.0000
227
6C
Beans
dry
great
northern
0.002000
1.000
1.000
228
6C
Beans
dry
kidney
0.002000
1.000
1.000
229
6C
Beans
dry
lima
0.002000
1.000
1.000
230
6C
Beans
dry
navy
(pea)
0.002000
1.000
1.000
231
6C
Beans
dry
other
0.002000
1.000
1.000
232
6C
Beans
dry
pinto
0.002000
1.000
1.000
233
6B
Beans
succulent
lima
1.000000
1.000
1.000
26
1.0000
234
6A
Beans
succulent
green
11
Uncooked
1.000000
1.000
1.000
24
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
24
1.0000
14
Boiled
1.000000
1.000
1.000
24
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
25
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
25
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
25
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
25
1.0000
44
Frozen:
Boiled
1.000000
1.000
1.000
25
1.0000
51
Cured:
NFS
(smoked/
p
1.000000
1.000
1.000
25
1.0000
235
6A
Beans
succulent
other
1.000000
1.000
1.000
25
1.0000
236
6A
Beans
succulent
yellow/
wax
14
Boiled
1.000000
1.000
1.000
24
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
25
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
25
1.0000
237
15
Corn/
pop
0.000100
1.000
1.000
238
15
Corn/
sweet
1.000000
1.000
1.000
73
1.0000
240
6C
Peas
(garden)
dry
0.013000
0.045
1.000
241
6AB
Peas
(garden)
green
11
Uncooked
1.000000
1.000
1.000
27
1.0000
12
Cooked:
NFS
1.000000
0.150
1.000
27
1.0000
13
Baked
1.000000
0.150
1.000
27
1.0000
14
Boiled
1.000000
0.150
1.000
27
1.0000
15
Fried
1.000000
0.150
1.000
27
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
28
1.0000
32
Canned:
Cooked
1.000000
0.150
1.000
28
1.0000
34
Canned:
Boiled
1.000000
0.150
1.000
28
1.0000
42
Frozen:
Cooked
Attachment
6
Acute
Dietary
Exposure
Analysis
:
Excluding
Peaches
107
1.000000
0.150
1.000
28
1.0000
44
Frozen:
Boiled
1.000000
0.150
1.000
28
1.0000
45
Frozen:
Fried
1.000000
0.150
1.000
28
1.0000
243
6C
Lentils
0.002000
1.000
1.000
244
6C
Mung
beans
(sprouts)
0.002000
1.000
1.000
245
O
Okra
12
Cooked:
NFS
1.000000
0.180
1.000
79
1.0000
14
Boiled
1.000000
0.050
1.000
79
1.0000
15
Fried
1.000000
0.180
1.000
79
1.0000
32
Canned:
Cooked
1.000000
0.180
1.000
79
1.0000
42
Frozen:
Cooked
1.000000
0.180
1.000
79
1.0000
44
Frozen:
Boiled
1.000000
0.050
1.000
79
1.0000
249
6C
Beans
dry
broadbeans
0.002000
1.000
1.000
250
6B
Beans
succulent
broadbeans
1.000000
1.000
1.000
24
1.0000
251
6C
Beans
dry
pigeon
beans
0.002000
1.000
1.000
253
6
Beans
unspecified
1.000000
1.000
1.000
24
1.0000
255
6A
Soybeans
sprouted
seeds
0.000015
0.330
1.000
99
1.0000
256
O
Beans
dry
hyacinth
0.002000
1.000
1.000
257
O
Beans
succulent
hyacinth
1.000000
1.000
1.000
24
1.0000
258
6C
Beans
dry
blackeye
peas/
cowpea
0.002000
1.000
1.000
259
6C
Beans
dry
garbanzo/
chick
pea
0.002000
1.000
1.000
260
O
Asparagus
1.000000
1.000
1.000
74
1.0000
266
15
Corn
grain
endosperm
0.000100
1.000
1.000
267
15
Corn
grain
bran
0.000100
1.000
1.000
268
15
Corn
grain/
sugar/
hfcs
0.000100
1.500
1.000
270
15
Rice
rough
(brown)
0.074000
1.000
1.000
271
15
Rice
milled
(white)
0.074000
0.030
1.000
275
15
Sorghum
(including
milo)
0.000015
1.000
1.000
100
1.0000
276
15
Wheat
rough
0.000015
1.000
1.000
100
1.0000
277
15
Wheat
germ
0.000015
1.000
1.000
278
15
Wheat
bran
0.000015
1.000
1.000
279
15
Wheat
flour
0.000015
1.000
1.000
280
15
Millet
0.000015
1.000
1.000
100
1.0000
282
1A
Sugar
beet
0.000400
0.040
1.000
287
6C
Guar
beans
1.000000
1.000
1.000
24
1.0000
289
15
Corn
grain
oil
0.000100
0.250
1.000
292
O
Flax
seed
0.000100
1.000
1.000
293
O
Peanuts
oil
0.000600
0.290
1.000
297
6A
Soybeans
oil
0.000015
0.010
1.000
298
O
Sunflower
oil
0.000400
0.670
1.000
Attachment
6
Acute
Dietary
Exposure
Analysis
:
Excluding
Peaches
108
300
O
Olive
oil
0.077000
0.810
1.000
303
6A
Soybean
other
0.000015
1.000
1.000
99
1.0000
304
6A
Soybeans
mature
seeds
dry
0.000015
1.000
1.000
99
1.0000
305
6A
Soybeans
flour
(full
fat)
0.000015
1.000
1.000
306
6A
Soybeans
flour
(low
fat)
0.000015
1.000
1.000
307
6A
Soybeans
flour
(defatted)
0.000015
1.000
1.000
315
O
Grapes
wine
and
sherry
1.000000
1.000
1.000
77
1.0000
318
D
Milk
nonfat
solids
0.030000
1.000
1.000
86
1.0000
319
D
Milk
fat
solids
0.030000
1.000
1.000
86
1.0000
320
D
Milk
sugar
(lactose)
0.030000
1.000
1.000
86
1.0000
321
M
Beef
meat
byproducts
3.675000
1.000
1.000
88
1.0000
322
M
Beef
other
organ
meats
3.675000
1.000
1.000
88
1.0000
323
M
Beef
dried
0.907000
1.920
1.000
86
1.0000
324
M
Beef
fat
w/
o
bones
0.368000
1.000
1.000
86
1.0000
325
M
Beef
kidney
3.675000
1.000
1.000
88
1.0000
326
M
Beef
liver
1.390000
1.000
1.000
87
1.0000
327
M
Beef
lean
(fat/
free)
w/
o
bones
0.907000
1.000
1.000
86
1.0000
328
M
Goat
meat
byproducts
3.675000
1.000
1.000
88
1.0000
329
M
Goat
other
organ
meats
3.675000
1.000
1.000
88
1.0000
330
M
Goat
fat
w/
o
bone
0.368000
1.000
1.000
86
1.0000
331
M
Goat
kidney
3.675000
1.000
1.000
88
1.0000
332
M
Goat
liver
1.390000
1.000
1.000
87
1.0000
333
M
Goat
lean
(fat/
free)
w/
o
bone
0.907000
1.000
1.000
86
1.0000
336
M
Sheep
meat
byproducts
3.675000
1.000
1.000
88
1.0000
337
M
Sheep
other
organ
meats
3.675000
1.000
1.000
88
1.0000
338
M
Sheep
fat
w/
o
bone
0.368000
1.000
1.000
86
1.0000
339
M
Sheep
kidney
3.675000
1.000
1.000
88
1.0000
340
M
Sheep
liver
1.390000
1.000
1.000
87
1.0000
341
M
Sheep
lean
(fat
free)
w/
o
bone
0.907000
1.000
1.000
86
1.0000
342
M
Pork
meat
byproducts
0.260000
1.000
1.000
92
1.0000
343
M
Pork
other
organ
meats
0.260000
1.000
1.000
92
1.0000
344
M
Pork
fat
w/
o
bone
0.026000
1.000
1.000
90
1.0000
345
M
Pork
kidney
0.260000
1.000
1.000
92
1.0000
346
M
Pork
liver
0.100000
1.000
1.000
91
1.0000
347
M
Pork
lean
(fat
free)
w/
o
bone
0.065000
1.000
1.000
89
1.0000
349
F
Fish
shellfish
0.250000
1.000
1.000
377
11
Apples
juice
concentrate
1.000000
3.000
1.000
50
1.0000
378
O
Bananas
juice
1.000000
1.000
1.000
75
1.0000
379
1A
Sugar
beet
molasses
0.000400
0.040
1.000
Attachment
6
Acute
Dietary
Exposure
Analysis
:
Excluding
Peaches
109
380
13A
Blackberries
juice
1.000000
1.000
1.000
63
1.0000
383
5B
Cabbage
savoy
12
Cooked:
NFS
1.000000
0.025
1.000
19
1.0000
384
4B
Celery
juice
1.000000
1.000
1.000
11
1.0000
388
15
Corn
grain/
sugar
molasses
0.000100
1.500
1.000
389
O
Cranberries
juice
concentrate
1.000000
3.300
1.000
76
1.0000
392
O
Grapes
juice
concentrate
1.000000
3.000
1.000
78
1.0000
398
D
Milk
based
water
0.030000
1.000
1.000
86
1.0000
403
O
Peanuts
butter
0.000600
1.890
1.000
404
11
Pears
juice
1.000000
0.370
1.000
52
1.0000
405
6B
Peas
succulent/
blackeye/
cowpea
12
Cooked:
NFS
1.000000
0.150
1.000
27
1.0000
14
Boiled
1.000000
0.150
1.000
27
1.0000
32
Canned:
Cooked
1.000000
0.150
1.000
28
1.0000
42
Frozen:
Cooked
1.000000
0.150
1.000
28
1.0000
406
O
Pineapples
juice
concentrate
1.000000
2.000
1.000
82
0.0250
95
0.4750
97
0.5000
407
1AB
Radishes
japanese
(daiken)
1.000000
1.000
1.000
5
1.0000
408
15
Rice
bran
0.074000
0.400
1.000
410
12
Apricot
juice
1.000000
1.000
1.000
55
1.0000
413
6A
Snowpeas
11
Uncooked
1.000000
1.000
1.000
27
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
27
1.0000
14
Boiled
1.000000
1.000
1.000
27
1.0000
15
Fried
1.000000
1.000
1.000
27
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
28
1.0000
415
9B
Squash
spaghetti
1.000000
1.000
1.000
40
1.0000
416
O
Strawberries
juice
1.000000
1.000
1.000
84
1.0000
417
O
Sunflower
seeds
1.000000
1.000
1.000
85
1.0000
420
10
Tangerines
juice
concentrate
1.000000
4.080
1.000
46
1.0000
423
8
Tomatoes
dried
1.000000
0.520
1.000
32
1.0000
424
M
Veal
fat
w/
o
bones
0.368000
1.000
1.000
86
1.0000
425
M
Veal
lean
(fat
free)
w/
o
bones
0.907000
1.000
1.000
86
1.0000
426
M
Veal
kidney
3.675000
1.000
1.000
88
1.0000
427
M
Veal
liver
1.390000
1.000
1.000
87
1.0000
428
M
Veal
other
organ
meats
3.675000
1.000
1.000
88
1.0000
429
M
Veal
dried
0.907000
1.920
1.000
86
1.0000
430
M
Veal
meat
byproducts
3.675000
1.000
1.000
88
1.0000
431
14
Walnut
oil
0.005400
1.000
1.000
436
9A
Watermelon
juice
1.000000
1.000
1.000
38
1.0000
437
15
Wheat
germ
oil
0.000015
1.000
1.000
439
9B
Wintermelon
Attachment
6
Acute
Dietary
Exposure
Analysis
:
Excluding
Peaches
110
1.000000
1.000
1.000
35
1.0000
441
10
Grapefruit
juice
concentrate
1.000000
4.580
1.000
43
1.0000
442
10
Lemons
juice
concentrate
1.000000
6.330
1.000
44
1.0000
443
10
Limes
juice
concentrate
1.000000
3.330
1.000
46
1.0000
448
10
Grapefruit
peel
1.000000
1.000
1.000
42
1.0000
480
O
Plantains
green
1.000000
1.000
1.000
75
1.0000
481
O
Plantains
dried
1.000000
3.900
1.000
75
1.0000
940
O
Peanuts
hulled
0.000600
1.000
1.000
Attachment
6
Acute
Dietary
Exposure
Analysis
:
Excluding
Peaches
111
Results
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
ACUTE
Analysis
for
CARBARYL
(1989
92
data)
Residue
file:
$$$
10carbarylfinal9
no
peaches.
RS7
Adjustment
factor
#2
NOT
used.
Analysis
Date:
04
04
2002/
15:
35:
25
Residue
file
dated:
04
03
2002/
14:
28:
13/
8
Daily
totals
for
food
and
foodform
consumption
used.
MC
iterations
=
1000
MC
list
in
residue
file
MC
seed
=
10
Run
Comment:
""
===============================================================================
Summary
calculations
(per
capita):
95th
Percentile
99th
Percentile
99.9th
Percentile
Exposure
%
aRfD
Exposure
%
aRfD
Exposure
%
aRfD
U.
S.
Population:
0.000485
4.85
0.001322
13.22
0.005451
54.51
All
infants:
0.000670
6.70
0.002971
29.71
0.007188
71.88
Nursing
infants
(<
1
yr
old):
0.000267
2.67
0.000941
9.41
0.006452
64.52
Non
nursing
infants
(<
1
yr
old):
0.000890
8.90
0.003260
32.60
0.007493
74.93
Children
1
6
yrs:
0.001278
12.78
0.002381
23.81
0.010164
101.64
Children
7
12
yrs:
0.000703
7.03
0.001496
14.96
0.008243
82.43
Females
13+
(preg/
not
nursing):
0.000431
4.31
0.000913
9.13
0.006439
64.39
Females
13+
(nursing):
0.000470
4.70
0.001469
14.69
0.008557
85.57
Females
13
19
(not
preg
or
nursing):
0.000328
3.28
0.000789
7.89
0.004096
40.96
Females
20+
(not
preg
or
nursing):
0.000286
2.86
0.000927
9.27
0.004597
45.97
Females
13
50
yrs:
0.000309
3.09
0.000890
8.90
0.004262
42.62
Males
13
19
yrs:
0.000420
4.20
0.000865
8.65
0.003535
35.35
Males
20+
yrs:
0.000309
3.09
0.000889
8.89
0.003949
39.49
Seniors
55+:
0.000290
2.90
0.000985
9.85
0.005456
54.56
Attachment
7.
Acute
Dietary
Exposure
Analysis:
Excluding
Apples
112
Residue
File
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
Acute
analysis
for
CARBARYL
Residue
file
name:
C:\$
MyFiles\
Carbaryl\
Rdf
files\$$$
10carbarylfinal9
no
apples.
RS7
Analysis
Date
04
15
2002
Residue
file
dated:
04
04
2002/
15:
38:
36/
8
Reference
dose
(aRfD)
=
0.01
mg/
kg
bw/
day
RDL
indices
and
parameters
for
Monte
Carlo
Analysis:
Index
Dist
Parameter
#1
Param
#2
Param
#3
Comment
#
Code
1
6
Gardenbeet.
rdf
2
6
Carrot.
rdf
3
6
chic
hors
parsnip
salsify.
rdf
4
6
Potato.
rdf
5
6
radishes.
rdf
6
6
Turnip.
rdf
7
6
sweetpotato.
rdf
8
6
topsgardenbeet.
rdf
9
6
topsradish.
rdf
10
6
Topsturnip.
rdf
11
6
celery.
rdf
12
6
spinach.
rdf
13
6
cannedspinach.
rdf
14
6
lettucehd.
rdf
15
6
lettuceleaf.
rdf
16
6
rhubarb.
rdf
17
6
broccoli.
rdf
18
6
brusselssprouts.
rdf
19
6
cabbage.
rdf
20
6
cauliflower.
rdf
21
6
collards.
rdf
22
6
mustards.
rdf
23
6
kohrabi.
rdf
24
6
beanssucculentfresh.
rdf
25
6
beanssucculentprocessed.
rdf
26
6
beanslima.
rdf
27
6
Peasfresh.
rdf
28
6
Peasprocessed.
rdf
29
6
alleggplant.
rdf
30
6
peppersnonbell.
rdf
31
6
allsweetpepper.
rdf
32
6
tomatoesPB.
rdf
33
6
tomatoesNB.
rdf
34
6
allcucumber.
rdf
35
6
melon.
rdf
36
6
cantaloupe.
rdf
37
6
honeydew.
rdf
38
6
allwatermelon.
rdf
39
6
pumpkin.
rdf
40
6
wintersquash.
rdf
41
6
allsummersquash.
rdf
42
6
citrus.
rdf
43
6
grapefruitjuice.
rdf
44
6
lemonjuice.
rdf
45
6
orangesdecomp.
rdf
46
6
limejuice.
rdf
47
6
orangejuice.
rdf
48
6
appledecomp.
rdf
49
6
apple.
rdf
50
6
applejuice.
rdf
51
6
peardecomp.
rdf
52
6
pear.
rdf
53
6
quince.
rdf
54
6
crabapple.
rdf
55
6
apricot.
rdf
56
6
Apricotss.
rdf
57
6
allsweetcherries.
rdf
58
6
alltartcherries.
rdf
59
6
nectarine.
rdf
60
6
peachSS.
rdf
61
6
Peach.
rdf
62
6
plum2.
rdf
63
6
blackberries.
rdf
64
6
allblueberry.
rdf
Attachment
7.
Acute
Dietary
Exposure
Analysis:
Excluding
Apples
113
65
6
boysenberry.
rdf
66
6
currant.
rdf
67
6
allraspberries.
rdf
68
6
almonds.
rdf
69
6
chestnut.
rdf
70
6
filbert.
rdf
71
6
pecan.
rdf
72
6
walnut.
rdf
73
6
corn.
rdf
74
6
allasparagus.
rdf
75
6
banana.
rdf
76
6
allcranberry.
rdf
77
6
grapes.
rdf
78
6
grapejuice.
rdf
79
6
okra.
rdf
80
6
olives.
rdf
81
6
pineappledecomp.
rdf
82
6
pineapplemexico.
rdf
83
6
pistachio.
rdf
84
6
strawberrypdp.
rdf
85
6
sunflower.
rdf
86
6
milk2.
rdf
87
6
ruminantliver2.
rdf
88
6
ruminantkidney2.
rdf
89
6
swinemeat2.
rdf
90
6
swinefat2.
rdf
91
6
swineliver2.
rdf
92
6
swinekidney2.
rdf
93
6
poultry.
rdf
94
6
eggs.
rdf
95
6
pineappleother.
rdf
96
6
Plumdecomp.
rdf
97
6
pineappledomestic.
rdf
98
6
appledried.
rdf
99
6
soybean.
rdf
100
6
wheat.
rdf
Food
Crop
Food
Def
Res
Adj.
Factors
RDL
Indices
and
Ratios
Code
Grp
Name
(ppm)
#1
#2
I#
1
Ratio#
1
I#
2
Ratio#
2
I#
3
Ratio#
3
1
13A
Blackberries
1.000000
1.000
1.000
63
1.0000
2
13A
Boysenberries
1.000000
1.000
1.000
65
1.0000
3
13A
Dewberries
1.000000
1.000
1.000
65
1.0000
4
13A
Loganberries
1.000000
1.000
1.000
65
1.0000
5
13A
Raspberries
1.000000
1.000
1.000
67
1.0000
6
13A
Youngberries
1.000000
1.000
1.000
65
1.0000
7
13B
Blueberries
1.000000
1.000
1.000
64
1.0000
8
O
Cranberries
1.000000
1.000
1.000
76
1.0000
9
O
Cranberries
juice
1.000000
1.100
1.000
76
1.0000
10
13B
Currants
1.000000
1.000
1.000
66
1.0000
11
13B
Elderberries
1.000000
1.000
1.000
66
1.0000
12
13B
Gooseberries
1.000000
1.000
1.000
66
1.0000
13
O
Grapes
1.000000
1.000
1.000
77
1.0000
14
O
Grapes
raisins
11
Uncooked
1.000000
2.170
1.000
77
1.0000
12
Cooked:
NFS
1.000000
1.370
1.000
77
1.0000
13
Baked
1.000000
1.370
1.000
77
1.0000
14
Boiled
1.000000
1.370
1.000
77
1.0000
18
Dried
1.000000
1.370
1.000
77
1.0000
42
Frozen:
Cooked
Attachment
7.
Acute
Dietary
Exposure
Analysis:
Excluding
Apples
114
1.000000
1.370
1.000
77
1.0000
15
O
Grapes
juice
1.000000
1.000
1.000
78
1.0000
16
13B
Huckleberries
1.000000
1.000
1.000
66
1.0000
17
O
Strawberries
1.000000
1.000
1.000
84
1.0000
20
10
Citrus
citron
1.000000
1.000
1.000
42
1.0000
22
10
Grapefruit
peeled
fruit
11
Uncooked
1.000000
1.000
1.000
45
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
45
1.0000
14
Boiled
0.000000
1.000
1.000
31
Canned:
NFS
1.000000
1.000
1.000
42
1.0000
23
10
Grapefruit
juice
1.000000
1.170
1.000
43
1.0000
24
10
Kumquats
1.000000
1.000
1.000
42
1.0000
26
10
Lemons
peeled
fruit
11
Uncooked
1.000000
1.000
1.000
45
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
45
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
42
1.0000
27
10
Lemons
peel
1.000000
1.190
1.000
42
1.0000
28
10
Lemons
juice
1.000000
1.110
1.000
44
1.0000
30
10
Limes
peeled
fruit
1.000000
1.000
1.000
45
1.0000
31
10
Limes
peel
1.000000
1.270
1.000
42
1.0000
32
10
Limes
juice
1.000000
1.110
1.000
46
1.0000
33
10
Oranges
juice
concentrate
1.000000
3.700
1.000
47
1.0000
34
10
Oranges
peeled
fruit
11
Uncooked
1.000000
1.000
1.000
45
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
45
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
42
1.0000
35
10
Oranges
peel
1.000000
1.270
1.000
42
1.0000
36
10
Oranges
juice
1.000000
1.000
1.000
47
1.0000
37
10
Tangelos
1.000000
1.000
1.000
45
1.0000
38
10
Tangerines
11
Uncooked
1.000000
1.000
1.000
45
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
42
1.0000
41
Frozen:
NFS
1.000000
1.000
1.000
42
1.0000
39
10
Tangerines
juice
1.000000
1.280
1.000
46
1.0000
40
14
Almonds
1.000000
1.000
1.000
68
1.0000
43
14
Chestnuts
1.000000
1.000
1.000
69
1.0000
44
14
Filberts
(hazelnuts)
1.000000
1.000
1.000
70
1.0000
48
14
Walnuts
1.000000
1.000
1.000
72
1.0000
50
O
Pistachio
nuts
1.000000
1.000
1.000
83
1.0000
55
11
Crabapples
1.000000
1.000
1.000
54
1.0000
56
11
Pears
11
Uncooked
1.000000
1.000
1.000
51
1.0000
Attachment
7.
Acute
Dietary
Exposure
Analysis:
Excluding
Apples
115
12
Cooked:
NFS
1.000000
1.000
1.000
51
1.0000
13
Baked
1.000000
1.000
1.000
51
1.0000
14
Boiled
1.000000
1.000
1.000
51
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
52
1.0000
57
11
Pears
dried
1.000000
2.600
1.000
52
1.0000
58
11
Quinces
1.000000
1.000
1.000
53
1.0000
59
12
Apricots
11
Uncooked
1.000000
1.000
1.000
56
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
56
1.0000
14
Boiled
1.000000
1.000
1.000
56
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
55
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
55
1.0000
60
12
Apricots
dried
1.000000
6.000
1.000
55
1.0000
61
12
Cherries
11
Uncooked
1.000000
1.000
1.000
57
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
58
1.0000
13
Baked
1.000000
1.000
1.000
58
1.0000
14
Boiled
1.000000
1.000
1.000
58
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
58
1.0000
33
Canned:
Baked
1.000000
1.000
1.000
58
1.0000
41
Frozen:
NFS
1.000000
1.000
1.000
58
1.0000
62
12
Cherries
dried
1.000000
4.000
1.000
57
1.0000
63
12
Cherries
juice
1.000000
1.500
1.000
58
1.0000
64
12
Nectarines
1.000000
1.000
1.000
59
1.0000
65
12
Peaches
11
Uncooked
1.000000
1.000
1.000
60
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
60
1.0000
13
Baked
1.000000
1.000
1.000
60
1.0000
14
Boiled
1.000000
1.000
1.000
60
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
61
1.0000
41
Frozen:
NFS
1.000000
1.000
1.000
61
1.0000
66
12
Peaches
dried
1.000000
7.000
1.000
61
1.0000
67
12
Plums
(damsons)
11
Uncooked
1.000000
1.000
1.000
96
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
96
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
62
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
62
1.0000
51
Cured:
NFS
(smoked/
p
1.000000
1.000
1.000
62
1.0000
68
12
Plums
prunes
(dried)
1.000000
0.150
1.000
62
1.0000
69
12
Plums/
prune
juice
1.000000
1.400
1.000
62
1.0000
72
O
Bananas
1.000000
1.000
1.000
75
1.0000
Attachment
7.
Acute
Dietary
Exposure
Analysis:
Excluding
Apples
116
73
O
Bananas
dried
1.000000
3.900
1.000
75
1.0000
81
11
Loquats
1.000000
1.000
1.000
53
1.0000
82
O
Olives
1.000000
1.000
1.000
80
1.0000
89
O
Pineapples
peeled
fruit
11
Uncooked
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
12
Cooked:
NFS
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
13
Baked
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
14
Boiled
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
31
Canned:
NFS
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
33
Canned:
Baked
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
41
Frozen:
NFS
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
90
O
Pineapples
dried
1.000000
5.000
1.000
82
0.0250
95
0.4750
97
0.5000
91
O
Pineapples
juice
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
94
O
Plantains
ripe
1.000000
1.000
1.000
75
1.0000
123
19A
Dill
0.004000
1.000
1.000
126
1AB
Horseradish
1.000000
1.000
1.000
3
1.0000
139
8
Paprika
1.000000
1.000
1.000
30
1.0000
141
9A
Melons
cantaloupes
juice
1.000000
1.000
1.000
36
1.0000
142
9A
Melons
cantaloupes
pulp
1.000000
1.000
1.000
36
1.0000
143
9A
Casabas
1.000000
1.000
1.000
35
1.0000
144
9A
Crenshaws
1.000000
1.000
1.000
35
1.0000
145
9A
Melons
honeydew
1.000000
1.000
1.000
37
1.0000
146
9A
Melons
persian
1.000000
1.000
1.000
35
1.0000
147
9A
Watermelon
1.000000
1.000
1.000
38
1.0000
148
9B
Cucumbers
1.000000
1.000
1.000
34
1.0000
149
9B
Pumpkin
1.000000
1.000
1.000
39
1.0000
150
9B
Squash
summer
1.000000
1.000
1.000
41
1.0000
151
9B
Squash
winter
1.000000
1.000
1.000
40
1.0000
152
9B
Bitter
melon
1.000000
1.000
1.000
35
1.0000
154
8
Eggplant
1.000000
1.000
1.000
29
1.0000
155
8
Peppers
sweet(
garden)
1.000000
1.000
1.000
31
1.0000
156
8
Peppers
chilli
incl
jalapeno
1.000000
1.000
1.000
30
1.0000
157
8
Peppers
other
1.000000
1.000
1.000
30
1.0000
158
8
Pimientos
1.000000
1.000
1.000
30
1.0000
159
8
Tomatoes
whole
11
Uncooked
1.000000
1.000
1.000
33
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
33
1.0000
13
Baked
1.000000
1.000
1.000
33
1.0000
14
Boiled
1.000000
1.000
1.000
33
1.0000
15
Fried
1.000000
1.000
1.000
33
1.0000
Attachment
7.
Acute
Dietary
Exposure
Analysis:
Excluding
Apples
117
31
Canned:
NFS
1.000000
1.000
1.000
32
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
32
1.0000
33
Canned:
Baked
1.000000
1.000
1.000
32
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
32
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
32
1.0000
160
8
Tomatoes
juice
1.000000
0.540
1.000
32
1.0000
161
8
Tomatoes
puree
1.000000
0.650
1.000
32
1.0000
162
8
Tomatoes
paste
1.000000
0.650
1.000
32
1.0000
163
8
Tomatoes
catsup
1.000000
0.650
1.000
32
1.0000
165
2
Beets
garden
tops(
greens)
1.000000
1.000
1.000
8
1.0000
166
4B
Celery
1.000000
1.000
1.000
11
1.0000
168
5A
Broccoli
1.000000
1.000
1.000
17
1.0000
169
5A
Brussels
sprouts
1.000000
1.000
1.000
18
1.0000
170
5A
Cabbage
green
and
red
11
Uncooked
1.000000
0.250
1.000
19
1.0000
12
Cooked:
NFS
1.000000
0.025
1.000
19
1.0000
13
Baked
1.000000
0.025
1.000
19
1.0000
14
Boiled
1.000000
0.025
1.000
19
1.0000
15
Fried
1.000000
0.025
1.000
19
1.0000
31
Canned:
NFS
1.000000
0.250
1.000
19
1.0000
32
Canned:
Cooked
1.000000
0.025
1.000
19
1.0000
51
Cured:
NFS
(smoked/
p
1.000000
0.025
1.000
19
1.0000
171
5A
Cauliflower
1.000000
1.000
1.000
20
1.0000
172
5B
Collards
1.000000
1.000
1.000
21
1.0000
174
5B
Kale
1.000000
1.000
1.000
22
1.0000
175
5A
Kohlrabi
1.000000
1.000
1.000
23
1.0000
176
4A
Lettuce
leafy
varieties
1.000000
1.000
1.000
15
1.0000
177
4A
Dandelion
greens
1.000000
1.000
1.000
12
1.0000
178
4A
Endive
curley
and
escarole
1.000000
1.000
1.000
15
1.0000
182
4A
Lettuce
unspecified
1.000000
1.000
1.000
14
1.0000
183
5B
Mustard
greens
1.000000
1.000
1.000
22
1.0000
184
4A
Parsley
1.000000
1.000
1.000
12
1.0000
185
4B
Rhubarb
1.000000
1.000
1.000
16
1.0000
186
4A
Spinach
11
Uncooked
1.000000
1.000
1.000
12
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
12
1.0000
13
Baked
0.000000
1.000
1.000
14
Boiled
1.000000
1.000
1.000
12
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
13
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
13
1.0000
Attachment
7.
Acute
Dietary
Exposure
Analysis:
Excluding
Apples
118
34
Canned:
Boiled
1.000000
1.000
1.000
13
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
12
1.0000
44
Frozen:
Boiled
1.000000
1.000
1.000
12
1.0000
187
4B
Swiss
chard
1.000000
1.000
1.000
16
1.0000
188
2
Turnips
tops
1.000000
1.000
1.000
10
1.0000
192
4A
Lettuce
head
varieties
1.000000
1.000
1.000
14
1.0000
195
O
Grapes
leaves
1.000000
1.000
1.000
77
1.0000
197
1AB
Beets
garden
roots
1.000000
1.000
1.000
1
1.0000
198
1AB
Carrots
1.000000
1.000
1.000
2
1.0000
207
1C
Potatoes/
white
whole
11
Uncooked
1.000000
1.000
1.000
4
1.0000
12
Cooked:
NFS
1.000000
0.040
1.000
4
1.0000
13
Baked
1.000000
1.200
1.000
4
1.0000
14
Boiled
1.000000
2.500
1.000
4
1.0000
15
Fried
1.000000
0.040
1.000
4
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
4
1.0000
208
1C
Potatoes/
white
unspecified
1.000000
1.000
1.000
4
1.0000
209
1C
Potatoes/
white
peeled
11
Uncooked
0.000000
1.000
1.000
12
Cooked:
NFS
1.000000
1.000
1.000
4
1.0000
13
Baked
1.000000
1.200
1.000
4
1.0000
14
Boiled
1.000000
2.500
1.000
4
1.0000
15
Fried
1.000000
0.040
1.000
4
1.0000
31
Canned:
NFS
0.000000
1.000
1.000
32
Canned:
Cooked
1.000000
1.000
1.000
4
1.0000
34
Canned:
Boiled
1.000000
2.500
1.000
4
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
4
1.0000
43
Frozen:
Baked
1.000000
1.200
1.000
4
1.0000
45
Frozen:
Fried
1.000000
0.040
1.000
4
1.0000
210
1C
Potatoes/
white
dry
0.000357
0.020
1.000
211
1C
Potatoes/
white
peel
only
13
Baked
1.000000
1.200
1.000
4
1.0000
15
Fried
1.000000
0.040
1.000
4
1.0000
212
1AB
Radishes
roots
1.000000
1.000
1.000
5
1.0000
213
2
Radishes
tops
1.000000
1.000
1.000
9
1.0000
214
1AB
Rutabagas
roots
1.000000
1.000
1.000
6
1.0000
215
2
Rutabagas
tops
1.000000
1.000
1.000
10
1.0000
216
1AB
Salsify(
oyster
plant)
1.000000
1.000
1.000
3
1.0000
218
1CD
Sweet
potatoes
(incl
yams)
1.000000
1.000
1.000
7
1.0000
219
1AB
Turnips
roots
1.000000
1.000
1.000
6
1.0000
220
1AB
Parsnips
Attachment
7.
Acute
Dietary
Exposure
Analysis:
Excluding
Apples
119
1.000000
1.000
1.000
3
1.0000
227
6C
Beans
dry
great
northern
0.002000
1.000
1.000
228
6C
Beans
dry
kidney
0.002000
1.000
1.000
229
6C
Beans
dry
lima
0.002000
1.000
1.000
230
6C
Beans
dry
navy
(pea)
0.002000
1.000
1.000
231
6C
Beans
dry
other
0.002000
1.000
1.000
232
6C
Beans
dry
pinto
0.002000
1.000
1.000
233
6B
Beans
succulent
lima
1.000000
1.000
1.000
26
1.0000
234
6A
Beans
succulent
green
11
Uncooked
1.000000
1.000
1.000
24
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
24
1.0000
14
Boiled
1.000000
1.000
1.000
24
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
25
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
25
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
25
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
25
1.0000
44
Frozen:
Boiled
1.000000
1.000
1.000
25
1.0000
51
Cured:
NFS
(smoked/
p
1.000000
1.000
1.000
25
1.0000
235
6A
Beans
succulent
other
1.000000
1.000
1.000
25
1.0000
236
6A
Beans
succulent
yellow/
wax
14
Boiled
1.000000
1.000
1.000
24
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
25
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
25
1.0000
237
15
Corn/
pop
0.000100
1.000
1.000
238
15
Corn/
sweet
1.000000
1.000
1.000
73
1.0000
240
6C
Peas
(garden)
dry
0.013000
0.045
1.000
241
6AB
Peas
(garden)
green
11
Uncooked
1.000000
1.000
1.000
27
1.0000
12
Cooked:
NFS
1.000000
0.150
1.000
27
1.0000
13
Baked
1.000000
0.150
1.000
27
1.0000
14
Boiled
1.000000
0.150
1.000
27
1.0000
15
Fried
1.000000
0.150
1.000
27
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
28
1.0000
32
Canned:
Cooked
1.000000
0.150
1.000
28
1.0000
34
Canned:
Boiled
1.000000
0.150
1.000
28
1.0000
42
Frozen:
Cooked
1.000000
0.150
1.000
28
1.0000
44
Frozen:
Boiled
1.000000
0.150
1.000
28
1.0000
45
Frozen:
Fried
1.000000
0.150
1.000
28
1.0000
243
6C
Lentils
0.002000
1.000
1.000
244
6C
Mung
beans
(sprouts)
0.002000
1.000
1.000
245
O
Okra
12
Cooked:
NFS
Attachment
7.
Acute
Dietary
Exposure
Analysis:
Excluding
Apples
120
1.000000
0.180
1.000
79
1.0000
14
Boiled
1.000000
0.050
1.000
79
1.0000
15
Fried
1.000000
0.180
1.000
79
1.0000
32
Canned:
Cooked
1.000000
0.180
1.000
79
1.0000
42
Frozen:
Cooked
1.000000
0.180
1.000
79
1.0000
44
Frozen:
Boiled
1.000000
0.050
1.000
79
1.0000
249
6C
Beans
dry
broadbeans
0.002000
1.000
1.000
250
6B
Beans
succulent
broadbeans
1.000000
1.000
1.000
24
1.0000
251
6C
Beans
dry
pigeon
beans
0.002000
1.000
1.000
253
6
Beans
unspecified
1.000000
1.000
1.000
24
1.0000
255
6A
Soybeans
sprouted
seeds
0.000015
0.330
1.000
99
1.0000
256
O
Beans
dry
hyacinth
0.002000
1.000
1.000
257
O
Beans
succulent
hyacinth
1.000000
1.000
1.000
24
1.0000
258
6C
Beans
dry
blackeye
peas/
cowpea
0.002000
1.000
1.000
259
6C
Beans
dry
garbanzo/
chick
pea
0.002000
1.000
1.000
260
O
Asparagus
1.000000
1.000
1.000
74
1.0000
266
15
Corn
grain
endosperm
0.000100
1.000
1.000
267
15
Corn
grain
bran
0.000100
1.000
1.000
268
15
Corn
grain/
sugar/
hfcs
0.000100
1.500
1.000
270
15
Rice
rough
(brown)
0.074000
1.000
1.000
271
15
Rice
milled
(white)
0.074000
0.030
1.000
275
15
Sorghum
(including
milo)
0.000015
1.000
1.000
100
1.0000
276
15
Wheat
rough
0.000015
1.000
1.000
100
1.0000
277
15
Wheat
germ
0.000015
1.000
1.000
278
15
Wheat
bran
0.000015
1.000
1.000
279
15
Wheat
flour
0.000015
1.000
1.000
280
15
Millet
0.000015
1.000
1.000
100
1.0000
282
1A
Sugar
beet
0.000400
0.040
1.000
287
6C
Guar
beans
1.000000
1.000
1.000
24
1.0000
289
15
Corn
grain
oil
0.000100
0.250
1.000
292
O
Flax
seed
0.000100
1.000
1.000
293
O
Peanuts
oil
0.000600
0.290
1.000
297
6A
Soybeans
oil
0.000015
0.010
1.000
298
O
Sunflower
oil
0.000400
0.670
1.000
300
O
Olive
oil
0.077000
0.810
1.000
303
6A
Soybean
other
0.000015
1.000
1.000
99
1.0000
304
6A
Soybeans
mature
seeds
dry
0.000015
1.000
1.000
99
1.0000
305
6A
Soybeans
flour
(full
fat)
0.000015
1.000
1.000
306
6A
Soybeans
flour
(low
fat)
0.000015
1.000
1.000
307
6A
Soybeans
flour
(defatted)
Attachment
7.
Acute
Dietary
Exposure
Analysis:
Excluding
Apples
121
0.000015
1.000
1.000
315
O
Grapes
wine
and
sherry
1.000000
1.000
1.000
77
1.0000
318
D
Milk
nonfat
solids
0.030000
1.000
1.000
86
1.0000
319
D
Milk
fat
solids
0.030000
1.000
1.000
86
1.0000
320
D
Milk
sugar
(lactose)
0.030000
1.000
1.000
86
1.0000
321
M
Beef
meat
byproducts
3.675000
1.000
1.000
88
1.0000
322
M
Beef
other
organ
meats
3.675000
1.000
1.000
88
1.0000
323
M
Beef
dried
0.907000
1.920
1.000
86
1.0000
324
M
Beef
fat
w/
o
bones
0.368000
1.000
1.000
86
1.0000
325
M
Beef
kidney
3.675000
1.000
1.000
88
1.0000
326
M
Beef
liver
1.390000
1.000
1.000
87
1.0000
327
M
Beef
lean
(fat/
free)
w/
o
bones
0.907000
1.000
1.000
86
1.0000
328
M
Goat
meat
byproducts
3.675000
1.000
1.000
88
1.0000
329
M
Goat
other
organ
meats
3.675000
1.000
1.000
88
1.0000
330
M
Goat
fat
w/
o
bone
0.368000
1.000
1.000
86
1.0000
331
M
Goat
kidney
3.675000
1.000
1.000
88
1.0000
332
M
Goat
liver
1.390000
1.000
1.000
87
1.0000
333
M
Goat
lean
(fat/
free)
w/
o
bone
0.907000
1.000
1.000
86
1.0000
336
M
Sheep
meat
byproducts
3.675000
1.000
1.000
88
1.0000
337
M
Sheep
other
organ
meats
3.675000
1.000
1.000
88
1.0000
338
M
Sheep
fat
w/
o
bone
0.368000
1.000
1.000
86
1.0000
339
M
Sheep
kidney
3.675000
1.000
1.000
88
1.0000
340
M
Sheep
liver
1.390000
1.000
1.000
87
1.0000
341
M
Sheep
lean
(fat
free)
w/
o
bone
0.907000
1.000
1.000
86
1.0000
342
M
Pork
meat
byproducts
0.260000
1.000
1.000
92
1.0000
343
M
Pork
other
organ
meats
0.260000
1.000
1.000
92
1.0000
344
M
Pork
fat
w/
o
bone
0.026000
1.000
1.000
90
1.0000
345
M
Pork
kidney
0.260000
1.000
1.000
92
1.0000
346
M
Pork
liver
0.100000
1.000
1.000
91
1.0000
347
M
Pork
lean
(fat
free)
w/
o
bone
0.065000
1.000
1.000
89
1.0000
349
F
Fish
shellfish
0.250000
1.000
1.000
378
O
Bananas
juice
1.000000
1.000
1.000
75
1.0000
379
1A
Sugar
beet
molasses
0.000400
0.040
1.000
380
13A
Blackberries
juice
1.000000
1.000
1.000
63
1.0000
383
5B
Cabbage
savoy
12
Cooked:
NFS
1.000000
0.025
1.000
19
1.0000
384
4B
Celery
juice
1.000000
1.000
1.000
11
1.0000
388
15
Corn
grain/
sugar
molasses
0.000100
1.500
1.000
389
O
Cranberries
juice
concentrate
1.000000
3.300
1.000
76
1.0000
392
O
Grapes
juice
concentrate
1.000000
3.000
1.000
78
1.0000
Attachment
7.
Acute
Dietary
Exposure
Analysis:
Excluding
Apples
122
398
D
Milk
based
water
0.030000
1.000
1.000
86
1.0000
402
12
Peaches
juice
1.000000
1.000
1.000
61
1.0000
403
O
Peanuts
butter
0.000600
1.890
1.000
404
11
Pears
juice
1.000000
0.370
1.000
52
1.0000
405
6B
Peas
succulent/
blackeye/
cowpea
12
Cooked:
NFS
1.000000
0.150
1.000
27
1.0000
14
Boiled
1.000000
0.150
1.000
27
1.0000
32
Canned:
Cooked
1.000000
0.150
1.000
28
1.0000
42
Frozen:
Cooked
1.000000
0.150
1.000
28
1.0000
406
O
Pineapples
juice
concentrate
1.000000
2.000
1.000
82
0.0250
95
0.4750
97
0.5000
407
1AB
Radishes
japanese
(daiken)
1.000000
1.000
1.000
5
1.0000
408
15
Rice
bran
0.074000
0.400
1.000
410
12
Apricot
juice
1.000000
1.000
1.000
55
1.0000
413
6A
Snowpeas
11
Uncooked
1.000000
1.000
1.000
27
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
27
1.0000
14
Boiled
1.000000
1.000
1.000
27
1.0000
15
Fried
1.000000
1.000
1.000
27
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
28
1.0000
415
9B
Squash
spaghetti
1.000000
1.000
1.000
40
1.0000
416
O
Strawberries
juice
1.000000
1.000
1.000
84
1.0000
417
O
Sunflower
seeds
1.000000
1.000
1.000
85
1.0000
420
10
Tangerines
juice
concentrate
1.000000
4.080
1.000
46
1.0000
423
8
Tomatoes
dried
1.000000
0.520
1.000
32
1.0000
424
M
Veal
fat
w/
o
bones
0.368000
1.000
1.000
86
1.0000
425
M
Veal
lean
(fat
free)
w/
o
bones
0.907000
1.000
1.000
86
1.0000
426
M
Veal
kidney
3.675000
1.000
1.000
88
1.0000
427
M
Veal
liver
1.390000
1.000
1.000
87
1.0000
428
M
Veal
other
organ
meats
3.675000
1.000
1.000
88
1.0000
429
M
Veal
dried
0.907000
1.920
1.000
86
1.0000
430
M
Veal
meat
byproducts
3.675000
1.000
1.000
88
1.0000
431
14
Walnut
oil
0.005400
1.000
1.000
436
9A
Watermelon
juice
1.000000
1.000
1.000
38
1.0000
437
15
Wheat
germ
oil
0.000015
1.000
1.000
439
9B
Wintermelon
1.000000
1.000
1.000
35
1.0000
441
10
Grapefruit
juice
concentrate
1.000000
4.580
1.000
43
1.0000
442
10
Lemons
juice
concentrate
1.000000
6.330
1.000
44
1.0000
443
10
Limes
juice
concentrate
1.000000
3.330
1.000
46
1.0000
448
10
Grapefruit
peel
1.000000
1.000
1.000
42
1.0000
480
O
Plantains
green
1.000000
1.000
1.000
75
1.0000
Attachment
7.
Acute
Dietary
Exposure
Analysis:
Excluding
Apples
123
481
O
Plantains
dried
1.000000
3.900
1.000
75
1.0000
940
O
Peanuts
hulled
0.000600
1.000
1.000
Attachment
7.
Acute
Dietary
Exposure
Analysis:
Excluding
Apples
124
Results
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
ACUTE
Analysis
for
CARBARYL
(1989
92
data)
Residue
file:
$$$
10carbarylfinal9
no
apples.
RS7
Adjustment
factor
#2
NOT
used.
Analysis
Date:
04
04
2002/
16:
22:
55
Residue
file
dated:
04
04
2002/
15:
38:
36/
8
Daily
totals
for
food
and
foodform
consumption
used.
MC
iterations
=
1000
MC
list
in
residue
file
MC
seed
=
10
Run
Comment:
""
===============================================================================
Summary
calculations
(per
capita):
95th
Percentile
99th
Percentile
99.9th
Percentile
Exposure
%
aRfD
Exposure
%
aRfD
Exposure
%
aRfD
U.
S.
Population:
0.000456
4.56
0.001246
12.46
0.004943
49.43
All
infants:
0.000544
5.44
0.003111
31.11
0.011784
117.84
Nursing
infants
(<
1
yr
old):
0.000209
2.09
0.000780
7.80
0.007620
76.20
Non
nursing
infants
(<
1
yr
old):
0.000774
7.74
0.003644
36.44
0.012798
127.98
Children
1
6
yrs:
0.001205
12.05
0.002248
22.48
0.008201
82.01
Children
7
12
yrs:
0.000672
6.72
0.001351
13.51
0.006867
68.67
Females
13+
(preg/
not
nursing):
0.000410
4.10
0.000788
7.88
0.004787
47.87
Females
13+
(nursing):
0.000385
3.85
0.001176
11.76
0.007275
72.75
Females
13
19
(not
preg
or
nursing):
0.000320
3.20
0.000778
7.78
0.003965
39.65
Females
20+
(not
preg
or
nursing):
0.000276
2.76
0.000901
9.01
0.004158
41.58
Females
13
50
yrs:
0.000298
2.98
0.000868
8.68
0.003890
38.90
Males
13
19
yrs:
0.000410
4.10
0.000819
8.19
0.003014
30.14
Males
20+
yrs:
0.000298
2.98
0.000848
8.48
0.003575
35.75
Seniors
55+:
0.000281
2.81
0.000963
9.63
0.005094
50.94
Attachment
8
Acute
Dietary
Exposure
Analysis:
Market
Basket
Survey:
All
Commodities
125
Residue
File
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
Acute
analysis
for
CARBARYL
Residue
file
name:
C:\$
MyFiles\
Carbaryl\
Rdf
files\$$$
10carbarylfinal9
market
basket.
RS7
Analysis
Date
04
15
2002
Residue
file
dated:
04
04
2002/
17:
32:
06/
8
Reference
dose
(aRfD)
=
0.01
mg/
kg
bw/
day
RDL
indices
and
parameters
for
Monte
Carlo
Analysis:
Index
Dist
Parameter
#1
Param
#2
Param
#3
Comment
#
Code
1
6
Gardenbeet.
rdf
2
6
Carrot.
rdf
3
6
chic
hors
parsnip
salsify.
rdf
4
6
Potato.
rdf
5
6
radishes.
rdf
6
6
Turnip.
rdf
7
6
sweetpotato.
rdf
8
6
topsgardenbeet.
rdf
9
6
topsradish.
rdf
10
6
Topsturnip.
rdf
11
6
celery.
rdf
12
6
spinach.
rdf
13
6
cannedspinach.
rdf
14
6
zmarklettuce.
rdf
15
6
lettuceleaf.
rdf
16
6
rhubarb.
rdf
17
6
zmarkbroccoli.
rdf
18
6
brusselssprouts.
rdf
19
6
cabbage.
rdf
20
6
cauliflower.
rdf
21
6
collards.
rdf
22
6
mustards.
rdf
23
6
kohrabi.
rdf
24
6
beanssucculentfresh.
rdf
25
6
beanssucculentprocessed.
rdf
26
6
beanslima.
rdf
27
6
Peasfresh.
rdf
28
6
Peasprocessed.
rdf
29
6
alleggplant.
rdf
30
6
peppersnonbell.
rdf
31
6
allsweetpepper.
rdf
32
6
tomatoesPB.
rdf
33
6
zmarktomato.
rdf
34
6
allcucumber.
rdf
35
6
melon.
rdf
36
6
cantaloupe.
rdf
37
6
honeydew.
rdf
38
6
allwatermelon.
rdf
39
6
pumpkin.
rdf
40
6
wintersquash.
rdf
41
6
allsummersquash.
rdf
42
6
citrus.
rdf
43
6
grapefruitjuice.
rdf
44
6
lemonjuice.
rdf
45
6
zmarkorange.
rdf
46
6
limejuice.
rdf
47
6
orangejuice.
rdf
48
6
zmarkapple.
rdf
49
6
apple.
rdf
50
6
applejuice.
rdf
51
6
peardecomp.
rdf
52
6
pear.
rdf
53
6
quince.
rdf
54
6
crabapple.
rdf
55
6
apricot.
rdf
56
6
Apricotdecomp.
rdf
57
6
allsweetcherries.
rdf
58
6
alltartcherries.
rdf
59
6
nectarine.
rdf
60
6
zmarkpeach.
rdf
61
6
Peach.
rdf
62
6
plum2.
rdf
63
6
blackberries.
rdf
64
6
allblueberry.
rdf
Attachment
8
Acute
Dietary
Exposure
Analysis:
Market
Basket
Survey:
All
Commodities
126
65
6
boysenberry.
rdf
66
6
currant.
rdf
67
6
allraspberries.
rdf
68
6
almonds.
rdf
69
6
chestnut.
rdf
70
6
filbert.
rdf
71
6
pecan.
rdf
72
6
walnut.
rdf
73
6
corn.
rdf
74
6
allasparagus.
rdf
75
6
zmarkbanana.
rdf
76
6
allcranberry.
rdf
77
6
zmarkgrape.
rdf
78
6
grapejuice.
rdf
79
6
okra.
rdf
80
6
olives.
rdf
81
6
pineappledecomp.
rdf
82
6
pineapplemexico.
rdf
83
6
pistachio.
rdf
84
6
allstrawberry.
rdf
85
6
sunflower.
rdf
86
6
milk2.
rdf
87
6
ruminantliver2.
rdf
88
6
ruminantkidney2.
rdf
89
6
swinemeat2.
rdf
90
6
swinefat2.
rdf
91
6
swineliver2.
rdf
92
6
swinekidney2.
rdf
93
6
poultry.
rdf
94
6
eggs.
rdf
95
6
pineappleother.
rdf
96
6
Plumdecomp.
rdf
97
6
pineappledomestic.
rdf
98
6
zmarkapricot.
rdf
99
6
zmarkcauliflower.
rdf
100
6
zmarkcitrus.
rdf
101
6
zmarkgrapefruit.
rdf
102
6
zmarkleaflettuce.
rdf
103
6
zmarklemon.
rdf
104
6
zmarknectarine.
rdf
105
6
zmarkpear.
rdf
106
6
zmarkplum.
rdf
107
6
zmarkquincecrabapp.
rdf
108
6
appledried.
rdf
109
6
soybean.
rdf
110
6
wheat.
rdf
Food
Crop
Food
Def
Res
Adj.
Factors
RDL
Indices
and
Ratios
Code
Grp
Name
(ppm)
#1
#2
I#
1
Ratio#
1
I#
2
Ratio#
2
I#
3
Ratio#
3
1
13A
Blackberries
1.000000
1.000
1.000
63
1.0000
2
13A
Boysenberries
1.000000
1.000
1.000
65
1.0000
3
13A
Dewberries
1.000000
1.000
1.000
65
1.0000
4
13A
Loganberries
1.000000
1.000
1.000
65
1.0000
5
13A
Raspberries
1.000000
1.000
1.000
67
1.0000
6
13A
Youngberries
1.000000
1.000
1.000
65
1.0000
7
13B
Blueberries
1.000000
1.000
1.000
64
1.0000
8
O
Cranberries
1.000000
1.000
1.000
76
1.0000
9
O
Cranberries
juice
1.000000
1.100
1.000
76
1.0000
10
13B
Currants
1.000000
1.000
1.000
66
1.0000
11
13B
Elderberries
1.000000
1.000
1.000
66
1.0000
12
13B
Gooseberries
1.000000
1.000
1.000
66
1.0000
13
O
Grapes
1.000000
1.000
1.000
77
1.0000
14
O
Grapes
raisins
11
Uncooked
Attachment
8
Acute
Dietary
Exposure
Analysis:
Market
Basket
Survey:
All
Commodities
127
1.000000
2.170
1.000
77
1.0000
12
Cooked:
NFS
1.000000
1.370
1.000
77
1.0000
13
Baked
1.000000
1.370
1.000
77
1.0000
14
Boiled
1.000000
1.370
1.000
77
1.0000
18
Dried
1.000000
1.370
1.000
77
1.0000
42
Frozen:
Cooked
1.000000
1.370
1.000
77
1.0000
15
O
Grapes
juice
1.000000
1.000
1.000
78
1.0000
16
13B
Huckleberries
1.000000
1.000
1.000
66
1.0000
17
O
Strawberries
1.000000
1.000
1.000
84
1.0000
20
10
Citrus
citron
1.000000
1.000
1.000
100
1.0000
22
10
Grapefruit
peeled
fruit
11
Uncooked
1.000000
1.000
1.000
101
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
101
1.0000
14
Boiled
0.000000
1.000
1.000
31
Canned:
NFS
1.000000
1.000
1.000
101
1.0000
23
10
Grapefruit
juice
1.000000
1.170
1.000
43
1.0000
24
10
Kumquats
1.000000
1.000
1.000
100
1.0000
26
10
Lemons
peeled
fruit
11
Uncooked
1.000000
1.000
1.000
103
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
103
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
103
1.0000
27
10
Lemons
peel
1.000000
1.190
1.000
103
1.0000
28
10
Lemons
juice
1.000000
1.110
1.000
44
1.0000
30
10
Limes
peeled
fruit
1.000000
1.000
1.000
100
1.0000
31
10
Limes
peel
1.000000
1.270
1.000
100
1.0000
32
10
Limes
juice
1.000000
1.110
1.000
46
1.0000
33
10
Oranges
juice
concentrate
1.000000
3.700
1.000
47
1.0000
34
10
Oranges
peeled
fruit
11
Uncooked
1.000000
1.000
1.000
45
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
45
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
45
1.0000
35
10
Oranges
peel
1.000000
1.270
1.000
45
1.0000
36
10
Oranges
juice
1.000000
1.000
1.000
47
1.0000
37
10
Tangelos
1.000000
1.000
1.000
100
1.0000
38
10
Tangerines
11
Uncooked
1.000000
1.000
1.000
100
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
100
1.0000
41
Frozen:
NFS
1.000000
1.000
1.000
100
1.0000
39
10
Tangerines
juice
1.000000
1.280
1.000
46
1.0000
40
14
Almonds
1.000000
1.000
1.000
68
1.0000
43
14
Chestnuts
1.000000
1.000
1.000
69
1.0000
44
14
Filberts
(hazelnuts)
Attachment
8
Acute
Dietary
Exposure
Analysis:
Market
Basket
Survey:
All
Commodities
128
1.000000
1.000
1.000
70
1.0000
48
14
Walnuts
1.000000
1.000
1.000
72
1.0000
50
O
Pistachio
nuts
1.000000
1.000
1.000
83
1.0000
52
11
Apples
11
Uncooked
1.000000
1.000
1.000
48
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
48
1.0000
13
Baked
1.000000
1.000
1.000
48
1.0000
14
Boiled
1.000000
1.000
1.000
48
1.0000
15
Fried
1.000000
1.000
1.000
48
1.0000
18
Dried
0.001400
1.000
1.000
108
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
48
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
48
1.0000
33
Canned:
Baked
1.000000
1.000
1.000
48
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
48
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
48
1.0000
53
11
Apples
dried
1.000000
2.600
1.000
48
1.0000
54
11
Apples
juice/
cider
1.000000
1.000
1.000
50
1.0000
55
11
Crabapples
1.000000
1.000
1.000
107
1.0000
56
11
Pears
11
Uncooked
1.000000
1.000
1.000
105
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
105
1.0000
13
Baked
1.000000
1.000
1.000
105
1.0000
14
Boiled
1.000000
1.000
1.000
105
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
105
1.0000
57
11
Pears
dried
1.000000
2.600
1.000
105
1.0000
58
11
Quinces
1.000000
1.000
1.000
107
1.0000
59
12
Apricots
11
Uncooked
1.000000
1.000
1.000
98
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
98
1.0000
14
Boiled
1.000000
1.000
1.000
98
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
98
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
98
1.0000
60
12
Apricots
dried
1.000000
6.000
1.000
98
1.0000
61
12
Cherries
11
Uncooked
1.000000
1.000
1.000
57
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
58
1.0000
13
Baked
1.000000
1.000
1.000
58
1.0000
14
Boiled
1.000000
1.000
1.000
58
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
58
1.0000
33
Canned:
Baked
1.000000
1.000
1.000
58
1.0000
41
Frozen:
NFS
1.000000
1.000
1.000
58
1.0000
62
12
Cherries
dried
Attachment
8
Acute
Dietary
Exposure
Analysis:
Market
Basket
Survey:
All
Commodities
129
1.000000
4.000
1.000
57
1.0000
63
12
Cherries
juice
1.000000
1.500
1.000
58
1.0000
64
12
Nectarines
1.000000
1.000
1.000
104
1.0000
65
12
Peaches
11
Uncooked
1.000000
1.000
1.000
60
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
60
1.0000
13
Baked
1.000000
1.000
1.000
60
1.0000
14
Boiled
1.000000
1.000
1.000
60
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
60
1.0000
41
Frozen:
NFS
1.000000
1.000
1.000
60
1.0000
66
12
Peaches
dried
1.000000
7.000
1.000
60
1.0000
67
12
Plums
(damsons)
11
Uncooked
1.000000
1.000
1.000
106
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
106
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
106
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
106
1.0000
51
Cured:
NFS
(smoked/
p
1.000000
1.000
1.000
106
1.0000
68
12
Plums
prunes
(dried)
1.000000
0.150
1.000
106
1.0000
69
12
Plums/
prune
juice
1.000000
1.400
1.000
106
1.0000
72
O
Bananas
1.000000
1.000
1.000
75
1.0000
73
O
Bananas
dried
1.000000
3.900
1.000
75
1.0000
81
11
Loquats
1.000000
1.000
1.000
107
1.0000
82
O
Olives
1.000000
1.000
1.000
80
1.0000
89
O
Pineapples
peeled
fruit
11
Uncooked
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
12
Cooked:
NFS
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
13
Baked
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
14
Boiled
1.000000
0.540
1.000
81
0.0250
95
0.4750
97
0.5000
31
Canned:
NFS
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
33
Canned:
Baked
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
41
Frozen:
NFS
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
90
O
Pineapples
dried
1.000000
5.000
1.000
82
0.0250
95
0.4750
97
0.5000
91
O
Pineapples
juice
1.000000
0.540
1.000
82
0.0250
95
0.4750
97
0.5000
94
O
Plantains
ripe
1.000000
1.000
1.000
75
1.0000
123
19A
Dill
0.004000
1.000
1.000
126
1AB
Horseradish
1.000000
1.000
1.000
3
1.0000
139
8
Paprika
1.000000
1.000
1.000
30
1.0000
141
9A
Melons
cantaloupes
juice
1.000000
1.000
1.000
36
1.0000
142
9A
Melons
cantaloupes
pulp
1.000000
1.000
1.000
36
1.0000
143
9A
Casabas
1.000000
1.000
1.000
35
1.0000
144
9A
Crenshaws
1.000000
1.000
1.000
35
1.0000
Attachment
8
Acute
Dietary
Exposure
Analysis:
Market
Basket
Survey:
All
Commodities
130
145
9A
Melons
honeydew
1.000000
1.000
1.000
37
1.0000
146
9A
Melons
persian
1.000000
1.000
1.000
35
1.0000
147
9A
Watermelon
1.000000
1.000
1.000
38
1.0000
148
9B
Cucumbers
1.000000
1.000
1.000
34
1.0000
149
9B
Pumpkin
1.000000
1.000
1.000
39
1.0000
150
9B
Squash
summer
1.000000
1.000
1.000
41
1.0000
151
9B
Squash
winter
1.000000
1.000
1.000
40
1.0000
152
9B
Bitter
melon
1.000000
1.000
1.000
35
1.0000
154
8
Eggplant
1.000000
1.000
1.000
29
1.0000
155
8
Peppers
sweet(
garden)
1.000000
1.000
1.000
31
1.0000
156
8
Peppers
chilli
incl
jalapeno
1.000000
1.000
1.000
30
1.0000
157
8
Peppers
other
1.000000
1.000
1.000
30
1.0000
158
8
Pimientos
1.000000
1.000
1.000
30
1.0000
159
8
Tomatoes
whole
11
Uncooked
1.000000
1.000
1.000
33
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
33
1.0000
13
Baked
1.000000
1.000
1.000
33
1.0000
14
Boiled
1.000000
1.000
1.000
33
1.0000
15
Fried
1.000000
1.000
1.000
33
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
33
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
33
1.0000
33
Canned:
Baked
1.000000
1.000
1.000
33
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
33
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
33
1.0000
160
8
Tomatoes
juice
1.000000
0.540
1.000
33
1.0000
161
8
Tomatoes
puree
1.000000
0.650
1.000
33
1.0000
162
8
Tomatoes
paste
1.000000
0.650
1.000
33
1.0000
163
8
Tomatoes
catsup
1.000000
0.650
1.000
33
1.0000
165
2
Beets
garden
tops(
greens)
1.000000
1.000
1.000
8
1.0000
166
4B
Celery
1.000000
1.000
1.000
11
1.0000
168
5A
Broccoli
1.000000
1.000
1.000
17
1.0000
169
5A
Brussels
sprouts
14
Boiled
1.000000
0.025
1.000
18
1.0000
42
Frozen:
Cooked
1.000000
0.025
1.000
18
1.0000
170
5A
Cabbage
green
and
red
11
Uncooked
1.000000
0.250
1.000
19
1.0000
12
Cooked:
NFS
1.000000
0.025
1.000
19
1.0000
13
Baked
1.000000
0.025
1.000
19
1.0000
14
Boiled
1.000000
0.025
1.000
19
1.0000
15
Fried
1.000000
0.025
1.000
19
1.0000
31
Canned:
NFS
Attachment
8
Acute
Dietary
Exposure
Analysis:
Market
Basket
Survey:
All
Commodities
131
1.000000
0.250
1.000
19
1.0000
32
Canned:
Cooked
1.000000
0.025
1.000
19
1.0000
51
Cured:
NFS
(smoked/
p
1.000000
0.250
1.000
19
1.0000
171
5A
Cauliflower
1.000000
1.000
1.000
99
1.0000
172
5B
Collards
1.000000
1.000
1.000
21
1.0000
174
5B
Kale
1.000000
1.000
1.000
22
1.0000
175
5A
Kohlrabi
14
Boiled
1.000000
0.025
1.000
23
1.0000
176
4A
Lettuce
leafy
varieties
1.000000
1.000
1.000
102
1.0000
177
4A
Dandelion
greens
1.000000
1.000
1.000
12
1.0000
178
4A
Endive
curley
and
escarole
1.000000
1.000
1.000
15
1.0000
182
4A
Lettuce
unspecified
1.000000
1.000
1.000
102
1.0000
183
5B
Mustard
greens
1.000000
1.000
1.000
22
1.0000
184
4A
Parsley
1.000000
1.000
1.000
12
1.0000
185
4B
Rhubarb
1.000000
1.000
1.000
16
1.0000
186
4A
Spinach
11
Uncooked
1.000000
1.000
1.000
12
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
12
1.0000
13
Baked
0.000000
1.000
1.000
14
Boiled
1.000000
1.000
1.000
12
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
13
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
13
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
13
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
12
1.0000
44
Frozen:
Boiled
1.000000
1.000
1.000
12
1.0000
187
4B
Swiss
chard
1.000000
1.000
1.000
16
1.0000
188
2
Turnips
tops
1.000000
1.000
1.000
10
1.0000
192
4A
Lettuce
head
varieties
1.000000
1.000
1.000
14
1.0000
195
O
Grapes
leaves
1.000000
1.000
1.000
77
1.0000
197
1AB
Beets
garden
roots
1.000000
1.000
1.000
1
1.0000
198
1AB
Carrots
1.000000
1.000
1.000
2
1.0000
207
1C
Potatoes/
white
whole
11
Uncooked
1.000000
1.000
1.000
4
1.0000
12
Cooked:
NFS
1.000000
0.040
1.000
4
1.0000
13
Baked
1.000000
1.200
1.000
4
1.0000
14
Boiled
1.000000
2.500
1.000
4
1.0000
15
Fried
1.000000
0.040
1.000
4
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
4
1.0000
208
1C
Potatoes/
white
unspecified
1.000000
1.000
1.000
4
1.0000
209
1C
Potatoes/
white
peeled
11
Uncooked
0.000000
1.000
1.000
12
Cooked:
NFS
Attachment
8
Acute
Dietary
Exposure
Analysis:
Market
Basket
Survey:
All
Commodities
132
1.000000
1.000
1.000
4
1.0000
13
Baked
1.000000
1.200
1.000
4
1.0000
14
Boiled
1.000000
2.500
1.000
4
1.0000
15
Fried
1.000000
0.040
1.000
4
1.0000
31
Canned:
NFS
0.000000
1.000
1.000
32
Canned:
Cooked
1.000000
1.000
1.000
4
1.0000
34
Canned:
Boiled
1.000000
2.500
1.000
4
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
4
1.0000
43
Frozen:
Baked
1.000000
1.200
1.000
4
1.0000
45
Frozen:
Fried
1.000000
0.040
1.000
4
1.0000
210
1C
Potatoes/
white
dry
0.000357
0.020
1.000
211
1C
Potatoes/
white
peel
only
13
Baked
1.000000
1.200
1.000
4
1.0000
15
Fried
1.000000
0.040
1.000
4
1.0000
212
1AB
Radishes
roots
1.000000
1.000
1.000
5
1.0000
213
2
Radishes
tops
1.000000
1.000
1.000
9
1.0000
214
1AB
Rutabagas
roots
1.000000
1.000
1.000
6
1.0000
215
2
Rutabagas
tops
1.000000
1.000
1.000
10
1.0000
216
1AB
Salsify(
oyster
plant)
1.000000
1.000
1.000
3
1.0000
218
1CD
Sweet
potatoes
(incl
yams)
1.000000
1.000
1.000
7
1.0000
219
1AB
Turnips
roots
1.000000
1.000
1.000
6
1.0000
220
1AB
Parsnips
1.000000
1.000
1.000
3
1.0000
227
6C
Beans
dry
great
northern
0.002000
1.000
1.000
228
6C
Beans
dry
kidney
0.002000
1.000
1.000
229
6C
Beans
dry
lima
0.002000
1.000
1.000
230
6C
Beans
dry
navy
(pea)
0.002000
1.000
1.000
231
6C
Beans
dry
other
0.002000
1.000
1.000
232
6C
Beans
dry
pinto
0.002000
1.000
1.000
233
6B
Beans
succulent
lima
1.000000
1.000
1.000
26
1.0000
234
6A
Beans
succulent
green
11
Uncooked
1.000000
1.000
1.000
24
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
24
1.0000
14
Boiled
1.000000
1.000
1.000
24
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
25
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
25
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
25
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
25
1.0000
44
Frozen:
Boiled
1.000000
1.000
1.000
25
1.0000
51
Cured:
NFS
(smoked/
p
1.000000
1.000
1.000
25
1.0000
235
6A
Beans
succulent
other
1.000000
1.000
1.000
25
1.0000
236
6A
Beans
succulent
yellow/
wax
Attachment
8
Acute
Dietary
Exposure
Analysis:
Market
Basket
Survey:
All
Commodities
133
14
Boiled
1.000000
1.000
1.000
24
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
25
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
25
1.0000
237
15
Corn/
pop
0.000100
1.000
1.000
238
15
Corn/
sweet
1.000000
1.000
1.000
73
1.0000
240
6C
Peas
(garden)
dry
0.013000
1.000
1.000
241
6AB
Peas
(garden)
green
11
Uncooked
1.000000
1.000
1.000
27
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
27
1.0000
13
Baked
1.000000
1.000
1.000
27
1.0000
14
Boiled
1.000000
1.000
1.000
27
1.0000
15
Fried
1.000000
1.000
1.000
27
1.0000
31
Canned:
NFS
1.000000
1.000
1.000
28
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
28
1.0000
34
Canned:
Boiled
1.000000
1.000
1.000
28
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
28
1.0000
44
Frozen:
Boiled
1.000000
1.000
1.000
28
1.0000
45
Frozen:
Fried
1.000000
1.000
1.000
28
1.0000
243
6C
Lentils
0.002000
1.000
1.000
244
6C
Mung
beans
(sprouts)
0.002000
1.000
1.000
245
O
Okra
12
Cooked:
NFS
1.000000
0.180
1.000
79
1.0000
14
Boiled
1.000000
0.050
1.000
79
1.0000
15
Fried
1.000000
0.180
1.000
79
1.0000
32
Canned:
Cooked
1.000000
0.180
1.000
79
1.0000
42
Frozen:
Cooked
1.000000
0.180
1.000
79
1.0000
44
Frozen:
Boiled
1.000000
0.050
1.000
79
1.0000
249
6C
Beans
dry
broadbeans
0.002000
1.000
1.000
250
6B
Beans
succulent
broadbeans
1.000000
1.000
1.000
24
1.0000
251
6C
Beans
dry
pigeon
beans
0.002000
1.000
1.000
253
6
Beans
unspecified
1.000000
1.000
1.000
24
1.0000
255
6A
Soybeans
sprouted
seeds
0.000015
0.330
1.000
109
1.0000
256
O
Beans
dry
hyacinth
0.002000
1.000
1.000
257
O
Beans
succulent
hyacinth
1.000000
1.000
1.000
24
1.0000
258
6C
Beans
dry
blackeye
peas/
cowpea
0.002000
1.000
1.000
259
6C
Beans
dry
garbanzo/
chick
pea
0.002000
1.000
1.000
260
O
Asparagus
1.000000
1.000
1.000
74
1.0000
266
15
Corn
grain
endosperm
0.000100
1.000
1.000
267
15
Corn
grain
bran
0.000100
1.000
1.000
268
15
Corn
grain/
sugar/
hfcs
0.000100
1.500
1.000
Attachment
8
Acute
Dietary
Exposure
Analysis:
Market
Basket
Survey:
All
Commodities
134
270
15
Rice
rough
(brown)
0.074000
1.000
1.000
271
15
Rice
milled
(white)
0.074000
0.030
1.000
275
15
Sorghum
(including
milo)
0.000015
1.000
1.000
110
1.0000
276
15
Wheat
rough
0.000015
1.000
1.000
110
1.0000
277
15
Wheat
germ
0.000015
0.650
1.000
278
15
Wheat
bran
0.000015
1.000
1.000
279
15
Wheat
flour
0.000015
0.100
1.000
280
15
Millet
0.000015
1.000
1.000
110
1.0000
282
1A
Sugar
beet
0.000400
0.040
1.000
287
6C
Guar
beans
1.000000
1.000
1.000
24
1.0000
289
15
Corn
grain
oil
0.000100
0.250
1.000
292
O
Flax
seed
0.000100
1.000
1.000
293
O
Peanuts
oil
0.000600
0.290
1.000
297
6A
Soybeans
oil
0.000015
0.005
1.000
298
O
Sunflower
oil
0.000400
0.030
1.000
300
O
Olive
oil
0.077000
0.810
1.000
303
6A
Soybean
other
0.000015
1.000
1.000
109
1.0000
304
6A
Soybeans
mature
seeds
dry
0.000015
1.000
1.000
109
1.0000
305
6A
Soybeans
flour
(full
fat)
0.000015
1.000
1.000
306
6A
Soybeans
flour
(low
fat)
0.000015
1.000
1.000
307
6A
Soybeans
flour
(defatted)
0.000015
1.000
1.000
315
O
Grapes
wine
and
sherry
1.000000
1.000
1.000
77
1.0000
318
D
Milk
nonfat
solids
0.030000
1.000
1.000
86
1.0000
319
D
Milk
fat
solids
0.030000
1.000
1.000
86
1.0000
320
D
Milk
sugar
(lactose)
0.030000
1.000
1.000
86
1.0000
321
M
Beef
meat
byproducts
3.675000
1.000
1.000
88
1.0000
322
M
Beef
other
organ
meats
3.675000
1.000
1.000
88
1.0000
323
M
Beef
dried
0.907000
1.920
1.000
86
1.0000
324
M
Beef
fat
w/
o
bones
0.368000
1.000
1.000
86
1.0000
325
M
Beef
kidney
3.675000
1.000
1.000
88
1.0000
326
M
Beef
liver
1.390000
1.000
1.000
87
1.0000
327
M
Beef
lean
(fat/
free)
w/
o
bones
0.907000
1.000
1.000
86
1.0000
328
M
Goat
meat
byproducts
3.675000
1.000
1.000
88
1.0000
329
M
Goat
other
organ
meats
3.675000
1.000
1.000
88
1.0000
330
M
Goat
fat
w/
o
bone
0.368000
1.000
1.000
86
1.0000
331
M
Goat
kidney
3.675000
1.000
1.000
88
1.0000
332
M
Goat
liver
1.390000
1.000
1.000
87
1.0000
333
M
Goat
lean
(fat/
free)
w/
o
bone
0.907000
1.000
1.000
86
1.0000
336
M
Sheep
meat
byproducts
3.675000
1.000
1.000
88
1.0000
Attachment
8
Acute
Dietary
Exposure
Analysis:
Market
Basket
Survey:
All
Commodities
135
337
M
Sheep
other
organ
meats
3.675000
1.000
1.000
88
1.0000
338
M
Sheep
fat
w/
o
bone
0.368000
1.000
1.000
86
1.0000
339
M
Sheep
kidney
3.675000
1.000
1.000
88
1.0000
340
M
Sheep
liver
1.390000
1.000
1.000
87
1.0000
341
M
Sheep
lean
(fat
free)
w/
o
bone
0.907000
1.000
1.000
86
1.0000
342
M
Pork
meat
byproducts
0.260000
1.000
1.000
92
1.0000
343
M
Pork
other
organ
meats
0.260000
1.000
1.000
92
1.0000
344
M
Pork
fat
w/
o
bone
0.026000
1.000
1.000
90
1.0000
345
M
Pork
kidney
0.260000
1.000
1.000
92
1.0000
346
M
Pork
liver
0.100000
1.000
1.000
91
1.0000
347
M
Pork
lean
(fat
free)
w/
o
bone
0.065000
1.000
1.000
89
1.0000
349
F
Fish
shellfish
0.250000
1.000
1.000
377
11
Apples
juice
concentrate
1.000000
3.000
1.000
50
1.0000
378
O
Bananas
juice
1.000000
1.000
1.000
75
1.0000
379
1A
Sugar
beet
molasses
0.000400
0.040
1.000
380
13A
Blackberries
juice
1.000000
1.000
1.000
63
1.0000
383
5B
Cabbage
savoy
12
Cooked:
NFS
1.000000
0.025
1.000
19
1.0000
384
4B
Celery
juice
1.000000
1.000
1.000
11
1.0000
388
15
Corn
grain/
sugar
molasses
0.000100
1.500
1.000
389
O
Cranberries
juice
concentrate
1.000000
3.300
1.000
76
1.0000
392
O
Grapes
juice
concentrate
1.000000
3.000
1.000
78
1.0000
398
D
Milk
based
water
0.030000
1.000
1.000
86
1.0000
402
12
Peaches
juice
1.000000
1.000
1.000
60
1.0000
403
O
Peanuts
butter
0.000600
1.890
1.000
404
11
Pears
juice
1.000000
0.370
1.000
105
1.0000
405
6B
Peas
succulent/
blackeye/
cowpea
12
Cooked:
NFS
1.000000
1.000
1.000
27
1.0000
14
Boiled
1.000000
1.000
1.000
27
1.0000
32
Canned:
Cooked
1.000000
1.000
1.000
28
1.0000
42
Frozen:
Cooked
1.000000
1.000
1.000
28
1.0000
406
O
Pineapples
juice
concentrate
1.000000
2.000
1.000
82
0.0250
95
0.4750
97
0.5000
407
1AB
Radishes
japanese
(daiken)
1.000000
1.000
1.000
5
1.0000
408
15
Rice
bran
0.074000
0.400
1.000
410
12
Apricot
juice
1.000000
1.000
1.000
98
1.0000
413
6A
Snowpeas
11
Uncooked
1.000000
1.000
1.000
27
1.0000
12
Cooked:
NFS
1.000000
1.000
1.000
27
1.0000
14
Boiled
1.000000
1.000
1.000
27
1.0000
15
Fried
1.000000
1.000
1.000
27
1.0000
42
Frozen:
Cooked
Attachment
8
Acute
Dietary
Exposure
Analysis:
Market
Basket
Survey:
All
Commodities
136
1.000000
1.000
1.000
28
1.0000
415
9B
Squash
spaghetti
1.000000
1.000
1.000
40
1.0000
416
O
Strawberries
juice
1.000000
1.000
1.000
84
1.0000
417
O
Sunflower
seeds
1.000000
1.000
1.000
85
1.0000
420
10
Tangerines
juice
concentrate
1.000000
4.080
1.000
46
1.0000
423
8
Tomatoes
dried
1.000000
0.520
1.000
33
1.0000
424
M
Veal
fat
w/
o
bones
0.368000
1.000
1.000
86
1.0000
425
M
Veal
lean
(fat
free)
w/
o
bones
0.907000
1.000
1.000
86
1.0000
426
M
Veal
kidney
3.675000
1.000
1.000
88
1.0000
427
M
Veal
liver
1.390000
1.000
1.000
87
1.0000
428
M
Veal
other
organ
meats
3.675000
1.000
1.000
88
1.0000
429
M
Veal
dried
0.907000
1.920
1.000
86
1.0000
430
M
Veal
meat
byproducts
3.675000
1.000
1.000
88
1.0000
431
14
Walnut
oil
0.005400
1.000
1.000
436
9A
Watermelon
juice
1.000000
1.000
1.000
38
1.0000
437
15
Wheat
germ
oil
0.000015
0.650
1.000
439
9B
Wintermelon
1.000000
1.000
1.000
35
1.0000
441
10
Grapefruit
juice
concentrate
1.000000
4.580
1.000
43
1.0000
442
10
Lemons
juice
concentrate
1.000000
6.330
1.000
44
1.0000
443
10
Limes
juice
concentrate
1.000000
3.330
1.000
46
1.0000
448
10
Grapefruit
peel
1.000000
1.000
1.000
101
1.0000
480
O
Plantains
green
1.000000
1.000
1.000
75
1.0000
481
O
Plantains
dried
1.000000
3.900
1.000
75
1.0000
940
O
Peanuts
hulled
0.000600
1.000
1.000
Attachment
8
Acute
Dietary
Exposure
Analysis:
Market
Basket
Survey:
All
Commodities
137
Results
1989
1992
Consumption
Data
Used
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
ACUTE
Analysis
for
CARBARYL
(1989
92
data)
Residue
file:
$$$
10carbarylfinal9
market
basket.
RS7
Adjustment
factor
#2
NOT
used.
Analysis
Date:
04
08
2002/
14:
18:
59
Residue
file
dated:
04
04
2002/
17:
32:
06/
8
Daily
totals
for
food
and
foodform
consumption
used.
MC
iterations
=
1000
MC
list
in
residue
file
MC
seed
=
10
Run
Comment:
""
===============================================================================
Summary
calculations
(per
capita):
95th
Percentile
99th
Percentile
99.9th
Percentile
Exposure
%
aRfD
Exposure
%
aRfD
Exposure
%
aRfD
U.
S.
Population:
0.000462
4.62
0.001241
12.41
0.004623
46.23
All
infants:
0.000593
5.93
0.002875
28.75
0.007272
72.72
Nursing
infants
(<
1
yr
old):
0.000265
2.65
0.000950
9.50
0.006218
62.18
Non
nursing
infants
(<
1
yr
old):
0.000764
7.64
0.003068
30.68
0.007951
79.51
Children
1
6
yrs:
0.001241
12.41
0.002280
22.80
0.007344
73.44
Children
7
12
yrs:
0.000680
6.80
0.001345
13.45
0.006238
62.38
Females
13+
(preg/
not
nursing):
0.000418
4.18
0.000825
8.25
0.004483
44.83
Females
13+
(nursing):
0.000411
4.11
0.001179
11.79
0.007629
76.29
Females
13
19
(not
preg
or
nursing):
0.000320
3.20
0.000776
7.76
0.003523
35.23
Females
20+
(not
preg
or
nursing):
0.000274
2.74
0.000867
8.67
0.003792
37.92
Females
13
50
yrs:
0.000299
2.99
0.000858
8.58
0.003546
35.46
Males
13
19
yrs:
0.000409
4.09
0.000815
8.15
0.002723
27.23
Males
20+
yrs:
0.000297
2.97
0.000836
8.36
0.003423
34.23
Seniors
55+:
0.000275
2.75
0.000905
9.05
0.004810
48.10
Attachment
8
Acute
Dietary
Exposure
Analysis:
Market
Basket
Survey:
All
Commodities
138
Results
1994
1998
Consumption
Data
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
ACUTE
Analysis
for
CARBARYL
(1994
98
data)
Residue
file:
$$$
10carbarylfinal9
market
basket.
RS7
Adjustment
factor
#2
NOT
used.
Analysis
Date:
04
08
2002/
15:
15:
48
Residue
file
dated:
04
04
2002/
17:
32:
06/
8
Daily
totals
for
food
and
foodform
consumption
used.
MC
iterations
=
1000
MC
list
in
residue
file
MC
seed
=
10
Run
Comment:
""
===============================================================================
Summary
calculations
(per
capita):
95th
Percentile
99th
Percentile
99.9th
Percentile
Exposure
%
aRfD
Exposure
%
aRfD
Exposure
%
aRfD
U.
S.
Population:
0.000465
4.65
0.001303
13.03
0.004865
48.65
All
infants:
0.000650
6.50
0.002630
26.30
0.008091
80.91
Nursing
infants
(<
1
yr
old):
0.000286
2.86
0.001101
11.01
0.006065
60.65
Non
nursing
infants
(<
1
yr
old):
0.000785
7.85
0.003051
30.51
0.008895
88.95
Children
1
6
yrs:
0.001348
13.48
0.002799
27.99
0.009481
94.81
Children
7
12
yrs:
0.000643
6.43
0.001214
12.14
0.004921
49.21
Females
13+
(preg/
not
nursing):
0.000378
3.78
0.000853
8.53
0.005102
51.02
Females
13+
(nursing):
0.000353
3.53
0.000799
7.99
0.007064
70.64
Females
13
19
(not
preg
or
nursing):
0.000301
3.01
0.000799
7.99
0.004039
40.39
Females
20+
(not
preg
or
nursing):
0.000279
2.79
0.000863
8.63
0.004298
42.98
Females
13
50
yrs:
0.000298
2.98
0.000878
8.78
0.004224
42.24
Males
13
19
yrs:
0.000402
4.02
0.000867
8.67
0.004515
45.15
Males
20+
yrs:
0.000311
3.11
0.000831
8.31
0.003359
33.59
Seniors
55+:
0.000279
2.79
0.000819
8.19
0.004649
46.49
Attachment
9:
Quantitative
Usage
Analysis
(QUA)
139
Quantitative
Usage
Analysis
for
Carbaryl
Case
Number:
0080
PC
Code:
56801
Date:
July
21,
1998
Analyst:
Frank
Hernandez
Based
on
available
pesticide
survey
usage
information
for
the
years
of
1987
through
1996,
an
annual
estimate
of
carbaryl
total
domestic
usage
averaged
approximately
two
and
one
half
million
pounds
active
ingredient
(a.
i.)
for
over
one
and
one
half
million
acres
treated.
Carbaryl
is
an
insecticide
with
its
largest
markets
in
terms
of
total
pounds
active
ingredient
allocated
to
pecans
(12%),
apples
(9%),
grapes(
6%),
oranges
(5%),
alfalfa
(5%),
and
corn
(4%).
Most
of
the
usage
is
in
AR,
CA,
GA,
IL,
IN,
MI,
MS,
OH,
OK,
and
TX.
Crops
with
a
high
percentage
of
the
total
U.
S.
planted
acres
treated
include
avocados
(67%),
Chinese
cabbage
(57%),
asparagus
(43%),
cranberries
(39%),
and
Brussels
sprouts
(33%).
Crops
with
less
than
1
percent
of
the
crop
treated
include
alfalfa,
dry
beans,
canola,
corn,
cotton,
flax,
oats,
pasture,
green
peas,
safflower,
sod,
sorghum,
soybeans,
sugar
cane,
sunflowers,
sweet
corn,
walnuts,
wheat,
and
woodland.
Attachment
9:
Quantitative
Usage
Analysis
(QUA)
140
Site
Acres
Grown
(000)
Acres
Treated
(000)
%
of
Crop
Treated
LB
AI
Applied
(000)
Average
Application
Rate
1
States
of
Most
Usage
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
lb
ai/
acre/
yr
#appl
/
yr
lb
ai/
A/
appl
(%
of
total
lb
ai
used
on
this
site)
Alfalfa
23,949
120
263
0.50
1.10
130
365
1.1
1.
0
1.1
NE
SD
OK
MT
ND
IL
77%
Almonds
429
7
16
1.
72
3.
61
16
49
2.
1
1.0
2.
1
CA
100%
Apples
572
131
175
22.92
30.59
230
282
1.8
1.
4
1.2
WA
MI
NY
CA
CT
IN
77%
Asparagus
88
38
77
43.35
86.69
46
117
1.2
1.
3
0.9
MI
WA
97%
Avocados
82
55
70
66.93
85.18
1
2
0.0
1.
5
0.0
Beans,
Dry
1,
802
12
51
0.65
2.86
6
28
0.
5
1.0
0.
5
CA
ND
CO
88%
Beans,
Lima,
Fresh
6
1
2
12.49
29.88
1
2
1.1
1.
2
0.9
GA
100%
Beans,
Snap,
Fresh
81
11
17
14.12
21.03
16
23
1.4
1.
6
0.9
NC
FL
84%
Beans,
Snap,
Proc.
228
24
36
10.39
15.83
28
43
1.2
1.
6
0.7
IL
St
OR
83%
Beets
12
2
3
16.87
27.45
1
2
0.5
1.
0
0.5
WI
TX
OR
94%
Blackberries
5
1
2
28.39
44.05
2
4
1.7
1.
0
1.7
OR
100%
Blueberries
59
13
26
22.43
44.85
26
53
2.0
1.
2
1.7
ME
MI
83%
Broccoli
114
5
10
4.
43
8.
86
4
8
0.
8
1.0
0.
8
CA
OR
TX
88%
Brussels
Sprouts
3
1
2
33.33
66.67
1
2
1.0
1.
1
0.9
Cabbage,
Chinese
9
5
7
57.47
80.46
1
2
0.2
1.
1
0.2
CA
90%
Cabbage,
Fresh
84
1
4
1.
78
4.
40
2
6
1.
6
1.6
1.
0
NC
NY
84%
Canola
39
0
2
0.31
4.64
0
1
0.5
1.
0
0.5
MT
100%
Cantaloupes
113
8
11
7.
27
9.
39
8
13
0.9
1.
1
0.8
CA
IL
GA
TX
83%
Carrots
107
4
6
3.67
5.75
9
23
2.
3
2.5
0.
9
WI
MI
MN
88%
Cauliflower
58
1
2
1.55
3.60
1
2
1.1
1.
0
1.1
OR
CA
WA
83%
Celery
37
1
2
2.97
6.13
2
4
1.8
1.
8
1.0
MI
WI
89%
Cherries,
Sweet
47
12
17
25.29
36.45
32
46
2.7
1.
4
1.9
WA
MI
CA
84%
Cherries,
Tart
49
6
11
11.79
23.59
13
27
2.3
1.
3
1.9
MI
NY
88%
Attachment
9:
Quantitative
Usage
Analysis
(QUA)
Site
Acres
Grown
(000)
Acres
Treated
(000)
%
of
Crop
Treated
LB
AI
Applied
(000)
Average
Application
Rate
1
States
of
Most
Usage
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
lb
ai/
acre/
yr
#appl
/
yr
lb
ai/
A/
appl
(%
of
total
lb
ai
used
on
this
site)
141
Citrus,
Other
51
2
3
2.
98
5.
65
5
12
3.2
1.
8
1.8
FL
86%
Collards
11
0
1
3.
72
10.13
0
1
0.9
1.
0
0.9
NJ
88%
Corn
72,284
82
164
0.11
0.23
110
228
1.3
1.
3
1.0
MO
NE
MS
IN
GA
IL
51%
Cotton
12,689
26
77
0.20
0.61
32
94
1.2
1.
1
1.1
TN
MS
TX
CA
83%
Cranberries
29
11
24
38.97
83.65
23
48
2.0
1.
0
2.0
WI
MA
95%
Cucumbers
146
20
46
14.03
31.83
23
51
1.1
1.
0
1.1
NC
OH
SC
NY
VA
DE
73%
Cucumbers,
Proc.
117
5
11
4.
69
9.
37
7
15
1.3
2.
2
0.6
NC
MI
85%
Eggplant
119
11
25
8.87
20.59
22
54
2.0
2.
1
1.0
FL
NJ
TX
IL
OR
CA
64%
Flax
188
1
2
0.46
0.91
1
2
1.1
1.
0
1.1
ND
100%
Grapefruit
194
8
11
4.
05
5.
59
18
20
2.
3
1.6
1.
4
FL
TX
95%
Grapes
825
64
97
7.77
11.81
150
217
2.3
1.
7
1.4
NY
CA
OR
PA
MI
AR
77%
Hay,
Other
33,427
91
267
0.27
0.80
87
273
1.0
1.
2
0.8
TX
SD
FL
NC
CA
LA
81%
Hazelnuts
(Filberts)
27
1
3
3.90
12.18
3
8
2.5
1.
0
2.5
Lemons
63
2
4
2.77
6.55
6
14
3.
4
1.3
2.
7
CA
91%
Lettuce,
Head
212
7
17
3.
08
8.
10
8
22
1.3
1.
2
1.1
CA
82%
Lots/
Farmsteads/
etc
24,815
58
152
0.23
0.61
60
174
1.0
2.
5
0.4
MA
AZ
FL
PA
TX
KY
62%
Melons,
Honeydew
27
5
12
19.09
43.69
4
10
0.
9
1.2
0.
7
CA
100%
Nectarines
29
4
7
12.11
24.22
15
30
4.2
1.
1
3.8
Oats/
Rye
6,133
8
18
0.
13
0.
29
6
13
0.7
1.
0
0.7
MN
MS
ND
TX
MT
MI
77%
Okra
3
1
3
32.36
94.03
2
6
1.9
1.
0
1.9
TX
84%
Olives
32
3
5
9.
61
15.42
16
26
5.3
1.
0
5.3
CA
100%
Onions,
Dry
157
6
18
3.
71
11.36
23
72
4.0
7.
0
0.6
MI
100%
Oranges
867
28
42
3.27
4.89
130
194
4.6
1.
3
3.4
CA
FL
99%
Attachment
9:
Quantitative
Usage
Analysis
(QUA)
Site
Acres
Grown
(000)
Acres
Treated
(000)
%
of
Crop
Treated
LB
AI
Applied
(000)
Average
Application
Rate
1
States
of
Most
Usage
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
lb
ai/
acre/
yr
#appl
/
yr
lb
ai/
A/
appl
(%
of
total
lb
ai
used
on
this
site)
142
Other
Crops
2,515
35
43
1.39
1.70
63
156
1.8
1.
3
1.4
CA
MA
TX
NJ
WA
MI
75%
Pasture
86,960
27
69
0.03
0.08
25
77
0.9
1.
0
0.9
NC
TX
SC
NE
LA
80%
Peaches
212
32
38
15.10
18.05
96
203
3.0
2.
9
1.0
GA
CA
TX
OK
SC
MI
68%
Peanuts
1,610
48
96
2.99
5.99
53
107
1.1
1.
4
0.8
GA
TX
NC
AL
VA
84%
Pears
78
2
5
2.
92
6.
43
3
8
1.
5
1.5
1.
0
WA
OR
CA
PA
NY
OH
73%
Peas,
Dry
249
6
22
2.
52
8.
97
6
22
1.0
1.
0
1.0
WA
ID
TX
93%
Peas,
Green
386
6
28
1.
59
7.
13
9
40
1.5
1.
0
1.5
MN
OR
83%
Peas,
Green,
Proc.
329
2
17
0.
62
5.
23
3
25
1.5
1.
0
1.5
OR
100%
Pecans
488
95
115
19.53
23.51
290
610
3.0
2.
2
1.4
GA
TX
OK
MS
AR
84%
Peppers,
Bell
55
6
11
10.15
20.30
9
22
1.
5
1.7
0.
9
FL
CA
MI
90%
Peppers,
Sweet
77
10
23
12.95
29.95
14
31
1.3
1.
0
1.3
CA
FL
KY
LA
IL
80%
Pistachios
52
9
20
16.84
38.06
32
72
3.6
1.
0
3.6
Plums
64
3
6
4.
68
9.
36
12
23
3.
8
1.0
3.
8
CA
81%
Potatoes
1,
421
24
38
1.70
2.68
34
50
1.4
1.
7
0.8
ND
WA
MI
ID
FL
NY
59%
Pumpkins
36
11
20
31.21
56.11
37
66
3.2
1.
6
2.0
IL
PA
IN
OH
83%
Raspberries
11
0
1
3.57
9.84
1
3
2.8
1.
0
2.8
OR
MI
92%
Rice
2,921
33
40
1.15
1.37
41
58
1.2
1.
1
1.1
TX
CA
80%
Safflower
113
1
7
0.98
5.96
0
3
0.4
1.
0
0.4
CA
100%
Sod
152
0
7
0.14
4.28
0
15
2.
2
1.0
2.
2
TX
NH
100%
Sorghum
11,280
23
47
0.21
0.41
31
62
1.3
1.
2
1.1
MO
KS
TX
LA
NE
MS
75%
Soybeans
62,879
101
210
0.16
0.33
86
174
0.9
1.
0
0.9
MN
NE
SD
MS
NC
IL
60%
Squash
53
6
14
11.25
26.77
8
19
1.
4
1.0
1.
4
NJ
FL
MI
CA
NY
TX
90%
Strawberries
51
8
12
16.02
23.62
24
55
2.9
2.
1
1.4
CA
FL
NC
PA
81%
Attachment
9:
Quantitative
Usage
Analysis
(QUA)
Site
Acres
Grown
(000)
Acres
Treated
(000)
%
of
Crop
Treated
LB
AI
Applied
(000)
Average
Application
Rate
1
States
of
Most
Usage
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
Wtd
Avg
Est
Max
lb
ai/
acre/
yr
#appl
/
yr
lb
ai/
A/
appl
(%
of
total
lb
ai
used
on
this
site)
143
Sugar
Beets
1,
415
23
54
1.60
3.80
34
126
1.5
1.
1
1.3
CA
TX
WA
MN
OR
84%
Sugarcane
852
0
1
0.04
0.07
0
0
0.2
1.
1
0.1
FL
100%
Sunflower
2,745
11
40
0.40
1.47
8
31
0.
7
1.1
0.
7
SD
ND
92%
Sweet
Corn,
Fresh
233
9
17
3.
84
7.
12
28
52
3.
1
2.5
1.
3
CA
MI
IL
82%
Sweet
Corn,
Proc.
544
3
21
0.
49
3.
81
8
63
3.0
2.
9
1.1
IL
100%
Sweet
Potatoes
85
16
35
18.47
40.90
25
55
1.6
1.
0
1.6
LA
MS
NC
82%
Tobacco
695
10
20
1.50
2.85
18
44
1.7
1.
5
1.1
NC
KY
SC
TN
IN
84%
Tomatoes,
Fresh
136
7
15
5.
40
10.80
14
35
1.9
2.
6
0.7
CA
FL
TX
87%
Tomatoes,
Proc.
329
48
88
14.47
26.86
72
135
1.5
1.
3
1.2
CA
97%
Walnuts
205
1
4
0.54
1.82
2
8
2.1
1.
1
1.9
CA
100%
Watermelons
258
33
38
12.71
14.79
16
33
0.5
1.
0
0.5
FL
IN
MS
TX
GA
76%
Wheat,
Spring
20,799
24
48
0.11
0.23
16
32
0.7
1.
0
0.6
ND
MN
MT
88%
Wheat,
Winter
45,854
50
106
0.11
0.23
44
78
0.9
1.
0
0.8
KY
NC
TX
WY
OR
MD
67%
Woodland
62,825
31
72
0.05
0.11
26
54
0.8
1.
2
0.7
PA
MI
FL
ND
OH
IA
79%
Total
1659.6
2464
2517.2
3926
COLUMN
HEADINGS
Wtd
Avg
=
Weighted
average
the
most
recent
years
and
more
reliable
data
are
weighted
more
heavily.
Est
Max
=
Estimated
maximum,
which
is
estimated
from
available
data.
Average
application
rates
are
calculated
from
the
weighted
averages.
NOTES
ON
TABLE
DATA
Usage
data
primarily
covers
1987
1996.
Calculations
of
the
above
numbers
may
not
appear
to
agree
because
they
are
displayed
as
rounded
to
the
nearest
1000
for
acres
treated
or
lb.
a.
i.
(Therefore
0
=
<
500)
to
two
decimal
percentage
points
for
%
of
crop
treated.
Other/
Crop
Groups
Citrus,
Other
includes
kumquats,
limes,
tangelos,
and
tangerines.
Other
Crops
include
ornamentals,
popcorn,
rapeseed/
canola,
and
safflower.
SOURCES:
EPA
data,
USDA,
and
National
Center
for
Food
and
Agricultural
Policy.
| epa | 2024-06-07T20:31:42.255468 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0007/content.txt"
} |
EPA-HQ-OPP-2002-0138-0008 | Supporting & Related Material | "2002-07-31T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
Office
of
Prevention,
Pesticides
and
Toxic
Substances
DATE:
May
24,
2002
TXR
#:
0050726
MEMORANDUM
SUBJECT:
CARBARYL:
UPDATED
TOXICOLOGY
CHAPTER
FOR
RED
FROM:
Virginia
A.
Dobozy,
VMD,
MPH,
Veterinary
Medical
Officer
Reregistration
Branch
I
Health
Effects
Division
(7509C)
THRU:
Whang
Phang,
PhD,
Branch
Senior
Scientist
Reregistration
Branch
I
Health
Effects
Division
(7509C)
TO:
Jeff
Dawson,
Risk
Assessor
Reregistration
Branch
I
Health
Effects
Division
(7509C)
and
Betty
Shackleford/
Anthony
Britten
Special
Review
and
Reregistration
Division
(7508C)
PC
Code:
056801
DP
Barcode:
D282980
Submission:
S615586
Case:
818954
Attached
is
the
Updated
Toxicology
Chapter
for
Carbaryl
for
the
RED.
It
replaces
the
chapter
dated
December
7,
1999.
CARBARYL
PC
Code:
056801
Updated
Toxicology
Disciplinary
Chapter
for
the
Reregistration
Eligibility
Decision
Document
Date
completed:
May
24,
2002
Health
Effects
Division
Office
of
Pesticide
Programs
U.
S.
Environmental
Protection
Agency
Arlington,
VA
22202
Prepared
by:
Virginia
A.
Dobozy,
VMD,
MPH
TABLE
OF
CONTENTS
1.
0
HAZARD
CHARACTERIZATION
................................................
4
2.
0
REQUIREMENTS..............................................................
6
3.
0
DATA
GAP(
S).................................................................
8
4.
0
HAZARD
ASSESSMENT
.......................................................
8
4.
1
Acute
Toxicity
...........................................................
8
4.
2
Subchronic
Toxicity.......................................................
8
4.
3
Prenatal
Developmental
Toxicity
...........................................
12
4.4
Reproductive
Toxicity
....................................................
13
4.
5
Chronic
Toxicity
........................................................
17
4.6
Carcinogenicity
.........................................................
19
4.
7
Mutagenicity
...........................................................
24
4.
8
Neurotoxicity...........................................................
27
4.
9
Metabolism
............................................................
32
5.0
TOXICITY
ENDPOINT
SELECTION
.............................................
36
5.1
See
Section
9.2
for
Endpoint
Selection
Table.
.................................
36
5.
2
Dermal
Absorption
.......................................................
36
5.3
Classification
of
Carcinogenic
Potential
......................................
36
6.
0
FQPA
CONSIDERATIONS
.....................................................
39
6.
1
Degree
of
Concern
Analysis
and
Residual
Uncertainties
.........................
39
6.2
Hazard
Based
Special
FQPA
Safety
Factor
Recommendation
.....................
40
7.
0
REFERENCES
...............................................................
41
8.
0
APPENDICES
................................................................
45
9.
1
Toxicity
Profile
Summary
Tables
...........................................
46
9.1.1
Acute
Toxicity
Table
...............................................
46
9.1.2
Subchronic,
Chronic
and
Other
Toxicity
Tables
..........................
46
9.2
Summary
of
Toxicological
Endpoint
Selection
for
Carbaryl
......................
51
4
1.0
HAZARD
CHARACTERIZATION
The
toxicology
data
base
is
of
good
quality
and
is
essentially
complete.
A
90
day
inhalation
study
with
cholinesterase
measurements
is
required.
The
database
provides
sufficient
information
for
selecting
toxicity
endpoints
for
risk
assessment
and
therefore,
supports
a
reregistration
eligibility
decision
for
the
currently
registered
uses.
Carbaryl
is
a
carbamate
insecticide.
Its
primary
mode
of
toxic
action
is
through
cholinesterase
inhibition
(ChEI)
after
single
or
multiple
exposures.
In
most
of
the
toxicology
studies
in
which
ChE
was
measured,
it
was
the
endpoint
used
to
set
the
Lowest
Observed
Adverse
Effect
Level
(LOAEL).
The
acute
toxicity
studies
showed
that
carbaryl
was
relatively
toxic
with
acute
oral
dosing
(Tox.
Category
II);
but
the
acute
dermal
and
inhalation
toxicities
were
low
(Tox.
Categories
III
and
IV,
respectively).
Carbaryl
was
not
a
dermal
or
eye
irritant
and
was
not
a
dermal
sensitizer.
The
neurotoxicity
data
showed
that
carbaryl
was
not
a
delayed
neurotoxicant
in
the
hen.
In
the
acute
neurotoxicity
study
in
the
rat
after
a
single
dose
of
10
mg/
kg
carbaryl,
ChEI
was
observed
in
plasma,
whole
blood,
red
blood
cells
(RBC)
and
brain.
At
the
next
higher
dose
(50
mg/
kg),
clinical
signs
typical
of
carbamate
toxicity
were
observed.
In
the
subchronic
neurotoxicity
study
after
90
days
of
administration,
clinical
signs
of
toxicity
were
seen
at
the
same
dose
(10
mg/
kg/
day)
as
plasma,
whole
blood,
RBC
and
brain
ChEI.
There
was
no
evidence
of
structural
neuropathology
in
these
studies.
No
subchronic
studies
in
the
rat
or
dog
are
available,
except
for
the
subchronic
neurotoxicity
study
in
rats
and
4
week
dermal
toxicity
studies
in
rats
(one
with
technical
chemical
and
two
with
formulations).
One
of
the
dermal
toxicity
studies
was
useful
for
risk
assessment.
In
this
study,
the
systemic
NOAEL
was
20
mg/
kg/
day
based
on
decreased
RBC
ChE
in
males
and
females
and
brain
ChE
in
males
at
50
mg/
kg/
day.
The
chronic
toxicity
data
showed
that,
in
dogs,
decreases
in
plasma,
RBC
and
brain
ChE
were
observed
at
10
mg/
kg/
day;
clinical
signs
of
toxicity
were
also
observed
in
both
sexes
at
31
mg/
kg/
day.
Brain
and
plasma
ChE
were
decreased
in
female
dogs
at
3.1
mg/
kg/
day.
In
the
mouse,
clinical
signs
of
toxicity
were
not
typical
of
ChEI,
but
there
was
ChEI
(plasma,
RBC
and
brain)
at
146
mg/
kg/
day.
In
the
chronic
toxicity
study
in
rats,
carbaryl
at
the
highest
dose
(350
mg/
kg/
day
in
males
and
485
mg/
kg/
day
in
females)
caused
a
variety
of
toxic
effects
in
the
liver,
kidneys
and
urinary
bladder.
It
also
induced
an
increase
in
the
incidence
of
thyroid
follicular
cell
hypertrophy
and
degeneration
of
sciatic
nerves
and
skeletal
muscle.
RBC
ChE
was
decreased
in
males
at
60
mg/
kg/
day
and
in
females
at
79
mg/
kg/
day.
The
lowest
LOAEL
in
the
chronic
studies
was
in
the
chronic
dog
study,
i.
e.,
3.1
mg/
kg/
day,
which
was
the
lowest
dose
in
females.
In
a
follow
up
5
week
study
in
dogs
to
clarify
the
NOAEL
for
ChEI,
plasma
ChE
was
decreased
in
males
at
3.83
mg/
kg/
day;
no
effects
were
observed
at
1.43
mg/
kg/
day.
In
a
prenatal
developmental
toxicity
study
in
the
rat,
maternal
toxicity
was
observed
at
the
same
dose
(10
mg/
kg/
day)
as
developmental
toxicity;
the
NOAEL
was
4
mg/
kg/
day.
Developmental
effects
included
decreased
fetal
body
weight
and
increased
incomplete
ossification
of
multiple
bones.
In
a
prenatal
developmental
toxicity
study
in
the
rabbit,
the
maternal
and
developmental
LOAELs
were
50
mg/
kg/
day
and
150
mg/
kg/
day,
respectively.
The
respective
NOAELs
were
5
mg/
kg/
day
and
50
mg/
kg/
day.
The
only
evidence
of
developmental
toxicity
was
a
decrease
in
fetal
body
weight.
These
studies
showed
no
evidence
of
a
qualitative
or
quantitative
increased
susceptibility.
In
the
reproduction
study,
there
was
evidence
of
a
quantitative
offspring
susceptibility.
The
LOAEL
for
parental
systemic
toxicity
was
1500
5
ppm
(92.43
124.33
mg/
kg/
day
for
males
and
110.78
135.54
mg/
kg/
day
for
females)
based
on
decreased
body
weight,
weight
gain,
and
feed
consumption.
The
NOAEL
was
300
ppm
(23.49
31.34
mg/
kg/
day
for
males
and
26.91
36.32
mg/
kg/
day
for
females).
The
LOAEL
for
offspring
toxicity
was
300
ppm
(23.49
31.34
mg/
kg/
day
for
males
and
26.91
36.32
mg/
kg/
day
for
females)
based
on
increased
numbers
of
F2
pups
with
no
milk
in
the
stomach
and
decreased
pup
survival.
The
NOAEL
was
75
ppm
(4.67
5.79
mg/
kg/
day
for
males
and
5.56
6.41
mg/
kg/
day
for
females).
In
the
developmental
neurotoxicity
study,
there
was
evidence
of
qualitative
susceptibility.
Clinical
signs
of
toxicity
and
plasma
and
brain
ChEI
were
seen
in
maternal
animals
at
the
same
dose
(10
mg/
kg/
day)
as
changes
in
brain
morphometric
measurements
(decreases
in
cerebellar
measurements
in
females
on
Day
11
post
partum)
were
observed
in
offspring;
however,
brain
measurements
were
not
conducted
at
the
next
lower
dose.
The
Health
Effects
Division's
(HED)
Cancer
Assessment
Review
Committee
(CARC)(
11/
7/
01)
classified
carbaryl
as
Likely
to
be
carcinogenic
in
humans
based
on
an
increased
incidence
of
hemangiosarcomas
in
male
mice
at
all
doses
tested
(100,
1000
and
8000
ppm).
The
Q1*,
based
on
the
CD
1
mouse
dietary
study
with
¾
Interspecies
Scaling
Factor,
is
8.75
x
10
4
(mg/
kg/
day)
1
in
human
equivalents.
In
addition
to
the
required
carcinogenicity
studies
in
mice
and
rats,
the
registrant
submitted
a
special
study
in
genetically
modified
mice.
Carbaryl
was
administered
to
heterozygous
p53
deficient
(knockout)
male
mice
in
the
diet
at
concentrations
of
up
to
4000
ppm
(716.6
mg/
kg/
day)
for
six
months.
There
was
no
evidence
of
neoplastic
or
preneoplastic
changes
in
the
vascular
tissues
of
any
organ.
A
model
validation
study
demonstrated
that
vascular
tumors
occur
in
heterozygous
p53
deficient
mice
within
six
months
of
administration
of
a
known
genotoxic
carcinogen
(urethane).
A
recent
review
of
the
data
from
the
submitted
studies
and
the
published
literature
show
that
carbaryl
is
clastogenic
in
vitro.
The
wide
variety
of
induced
aberrations
(both
simple
and
complex)
was
consistent
between
the
submitted
micronucleus
study
and
the
open
literature.
However,
there
are
inconsistencies
relative
to
the
requirement
for
S9
activation.
Nevertheless,
the
two
in
vivo
studies
for
micronuclei
induction
or
chromosome
aberrations
were
negative.
Similarly,
the
6
month
p53
knockout
transgenic
mouse
bioassay
was
negative.
Carbaryl
was
also
negative
for
DNA
binding
in
the
livers
of
mice
treated
with
8000
ppm
for
2
weeks.
Metabolism
studies
identified
epoxide
intermediates
of
carbaryl
which
were
found
to
be
conjugated
to
glucuronide,
rapidly
metabolized
and
excreted
as
any
endogenous
epoxide
would
be.
Overall,
these
findings
indicate
that
carbaryl
produces
epoxides
and
its
DNA
reactivity
is
manifested
as
chromosomal
aberrations
in
cultured
mammalian
cells.
Other
in
vitro
studies
indicate
carbaryl's
effects
on
karyokinesis
and
cytokinesis,
as
well
as
stress
genes
associated
with
oxidative
damage.
Based
on
these
considerations,
the
CARC
concluded
that
there
is
a
concern
for
mutagenicity,
which
is
somewhat
lessened
because
of
the
lack
of
an
effect
in
in
vivo
mutagenicity
studies.
The
metabolism
data
in
the
rat
indicated
that
radiolabeled
carbaryl
was
readily
absorbed
with
oral
dosing,
distributed
to
various
organs,
metabolized
and
formed
conjugated
metabolites
with
compounds
such
glucuronic
acid.
A
total
of
20
components
was
found,
and
2
major
metabolites
were
identified,
naphthyl
sulfate
and
naphthyl
glucuronide.
Much
of
the
radioactivity
was
eliminated
within
24
hours
after
dosing
(86%
in
urine
and
11%
in
feces).
Seven
days
post
dosing,
negligible
amounts
of
the
administered
dose
were
found
in
tissues.
Several
special
metabolism
studies
were
conducted
to
explore
a
mechanism
for
the
increase
in
tumor
incidence
in
mice.
The
results
appear
to
show
that
high
doses
of
carbaryl
treatment
(1154
mg/
kg)
led
to
a
"phenobarbital"
type
of
induction
of
liver
xenobiotic
metabolizing
enzymes
and
6
interaction
of
carbaryl
with
chromatin
protein
in
mice.
A
dermal
absorption
study
indicated
that
12.7%
of
a
carbaryl
formulation
(43.9%
a.
i.)
was
absorbed
systemically.
2.0
REQUIREMENTS
The
requirements
(CFR
158.340)
for
food
use
for
CARBARYL
are
in
Table
1.
Inclusion
of
the
new
guideline
numbers
does
not
imply
that
the
new
(1998)
guideline
protocols
were
used.
7
Table
1.
Carbaryl
Data
Requirements
Test
Technical
Required
Satisfied
870.1100
Acute
Oral
Toxicity
...........................
870.1200
Acute
Dermal
Toxicity
........................
870.1300
Acute
Inhalation
Toxicity
......................
870.2400
Primary
Eye
Irritation
.........................
870.2500
Primary
Dermal
Irritation
......................
870.2600
Dermal
Sensitization
..........................
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
870.3100
Oral
Subchronic
(rodent)
.......................
870.3150
Oral
Subchronic
(nonrodent)
....................
870.3200
21
Day
Dermal
..............................
870.3250
90
Day
Dermal
..............................
870.3465
90
Day
Inhalation
............................
yes
yes
yes
no
yes
yes
a
yes
b
yes
c
no
no
870.3700a
Developmental
Toxicity
(rodent)
.................
870.3700b
Developmental
Toxicity
(nonrodent)
..............
870.3800
Reproduction
................................
yes
yes
yes
yes
yes
yes
870.4100a
Chronic
Toxicity
(rodent)
......................
870.4100b
Chronic
Toxicity
(nonrodent)
...................
870.4200a
Oncogenicity
(rat)
............................
870.4200b
Oncogenicity
(mouse)
.........................
870.4300
Chronic/
Oncogenicity
.........................
yes
yes
yes
yes
yes
yes
b
yes
yes
b
yes
yes
870.5100
Mutagenicity—
Gene
Mutation
bacterial
..........
870.5300
Mutagenicity—
Gene
Mutation
mammalian
.......
870.5385
Mutagenicity—
Structural
Chromosomal
Aberrations
870.5550
Mutagenicity—
Other
Genotoxic
Effects
...........
yes
yes
yes
yes
yes
yes
yes
d
yes
870.6100a
Acute
Delayed
Neurotox.
(hen)
..................
870.6100b
90
Day
Neurotoxicity
(hen)
.....................
870.6200a
Acute
Neurotox.
Screening
Battery
(rat)
...........
870.6200b
90
Day
Neuro.
Screening
Battery
(rat)
............
870.6300
Develop.
Neuro
..............................
yes
no
yes
yes
yes
yes
no
yes
yes
yes
870.7485
General
Metabolism
..........................
870.7600
Dermal
Penetration
...........................
yes
yes
yes
yes
Special
Studies
for
Ocular
Effects
Acute
Oral
(rat)
..............................
Subchronic
Oral
(rat)..........................
Six
month
Oral
(dog)
..........................
no
no
no
a
Satisfied
with
chronic
toxicity
study
b
Satisfied
with
combined
chronic
toxicity/
carcinogenicity
study
c
Satisfied
with
4
week
non
guideline
study
which
was
satisfactory
for
risk
assessment
d
Micronucleus
study
required
by
the
CARC
was
unacceptable
because
the
doses
were
not
high
enough.
However,
two
studies
from
the
open
literature
tested
carbaryl
up
to
the
LD50
or
1/
3
of
the
LD50,
which
was
higher
than
the
high
dose
in
the
submitted
study
and
negative.
8
3.0
DATA
GAP(
S)
90
day
inhalation
study
with
cholinesterase
measurements
4.0
HAZARD
ASSESSMENT
4.1
Acute
Toxicity
Adequacy
of
data
base
for
acute
toxicity:
The
data
base
for
acute
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
The
chemical
is
moderately
acutely
toxic
by
the
oral
route
(Toxicity
Category
II),
relatively
nontoxic
by
the
dermal
and
inhalation
routes
(Toxicity
Category
III
and
IV,
respectively),
not
a
primary
eye
or
skin
irritant
or
a
dermal
sensitizer.
The
acute
toxicity
data
on
CARBARYL
Technical
is
summarized
below
in
Table
2.
Table
2.
Acute
Toxicity
Data
on
CARBARYL
Guideline
No.
Study
Type
MRIDs
#
Results
Toxicity
Category
81
1
Acute
Oral
rat
00148500
LD50
for
males
=
302.6
mg/
kg;
for
females
=
311.5
mg/
kg;
combined
=
301.0
mg/
kg
II
81
2
Acute
Dermal
rabbit
00148501
LD50
>
2000
mg/
kg
III
81
3
Acute
Inhalation
rat
00148502
LC50
>
3.4
mg/
L
IV
81
4
Primary
Eye
Irritation
00148503
not
a
primary
eye
irritant
IV
81
5
Primary
Skin
Irritation
00148504
not
a
primary
skin
irritant
IV
81
6
Dermal
Sensitization
00148505
negative
4.2
Subchronic
Toxicity
Adequacy
of
data
base
for
Subchronic
Toxicity:
There
are
no
acceptable
subchronic
toxicity
studies
in
rodents
or
nonrodents.
However,
there
are
acceptable
chronic
studies,
including
a
chronic
toxicity
study
in
the
dog
and
a
combined
chronic
toxicity/
carcinogenicity
study
in
the
rat.
Therefore,
the
requirements
for
subchronic
toxicity
studies
in
dogs
and
rats
can
be
waived.
There
is
an
acceptable
subchronic
neurotoxicity
study
in
the
rat
(discussed
under
G.
Neurotoxicity).
Three
4
week
non
guideline
9
dermal
toxicity
studies
in
the
rat
were
conducted.
One
with
technical
carbaryl
was
classified
as
acceptable/
non
guideline
and
was
used
for
the
risk
assessment.
The
other
two
with
formulations
were
classified
as
unacceptable/
non
guideline.
No
additional
dermal
toxicity
studies
are
required
at
this
time.
MRID
45630601
In
a
non
guideline
four
week
dermal
toxicity
study
(MRID
45630601),
Carbaryl
Technical
(99.49%
a.
i.,
Lot
211048078)
was
applied
to
the
shaved
skin
of
10
Crl:
CD
(SD)
IGS
BR
rats/
sex/
dose
at
dose
levels
of
0,
20,
50
or
100
mg/
kg
bw/
day,
6
hours/
day
for
5
days/
week
during
a
4
week
period.
The
parameters
measured
included
the
following:
clinical
observations,
body
weight,
body
weight
gain,
food
consumption,
RBC
and
brain
cholinesterase
and
signs
of
dermal
irritation.
There
was
no
treatment
related
effect
on
mortality,
clinical
observations,
body
weight
or
dermal
irritation.
The
only
statistically
significant
body
weight
gain
changes
were
a
decrease
(27%)
in
the
100
mg/
kg/
day
males
during
Days
5
to
12
and
an
increase
(37%)
in
50
mg/
kg/
day
males
during
Days
19
to
26.
However,
there
were
non
significant
decreases
in
the
100
mg/
kg/
day
males
at
Days
3
to
5
(16%),
12
to
19
(17%)
and
3
to
26
(12%)
which
are
considered
toxicologically
significant.
The
only
statistically
significant
decreases
in
food
consumption
were
in
the
50
mg/
kg/
day
females
on
Days
12
to
19
and
50
and
in
the
100
mg/
kg/
day
females
on
Days
19
to
26.
The
effects
are
not
considered
treatment
related
as
there
was
no
dose
response
and
the
decreases
were
minimal
(9%
and
8%
in
the
50
and
100
mg/
kg/
day
groups,
respectively).
RBC
cholinesterase
was
measured
before
dosing
on
Day
4
and
on
Days
1,
8,
15
and
22.
The
only
statistically
significant
effects
were
in
the
100
mg/
kg/
day
males
at
Days
8
(11%
decrease)
and
22
(13%).
Using
the
repeated
measures
statistical
test,
there
were
also
significant
decreases
in
the
50
and
100
mg/
kg/
day
females
(11%
and
10%,
respectively)
on
Day
22.
These
effects
were
determined
to
be
not
toxicologically
significant
because
they
were
inconsistent.
Measurements
were
also
performed
within
1
hour
after
test
material
removal
on
Days
5,
12,
19,
and
26.
Statistically
significant
decreases
were
observed
in
the
50
mg/
kg/
day
(12%
decrease)
and
100
mg/
kg/
day
(15%)
males
on
Day
5
and
in
the
100
mg/
kg/
day
males
on
Days
12
(21%)
and
19
(16%).
Using
the
repeated
measures
statistical
test,
there
was
also
a
significant
decrease
(10%)
in
the
50
mg/
kg/
day
males
on
Day
12.
In
females,
statistically
significant
decreases
were
observed
in
the
50
and
100
mg/
kg/
day
groups
on
Days
5
(13%
and
12%,
respectively)
and
Day
12
(20%
and
13%,
respectively).
Brain
cholinesterase
was
statistically
significantly
decreased
in
the
50
mg/
kg/
day
males
(15%)
and
in
the
100
mg/
kg/
day
males
(15%)
and
females
(24%).
There
was
also
a
non
significant
decrease
in
the
50
mg/
kg/
day
females
(9%).
The
systemic
LOAEL
is
conservatively
established
at
50
mg/
kg/
day
based
on
statistically
significant
decreases
in
RBC
cholinesterase
in
males
and
females
and
brain
cholinesterase
in
males.
The
systemic
NOAEL
is
20
mg/
kg/
day.
10
The
dermal
LOAEL
was
not
established.
The
dermal
NOAEL
was
100
mg/
kg/
day.
This
4
week
dermal
toxicity
study
in
the
rat
is
acceptable
(non
guideline).
The
study
was
intended
to
establish
endpoints
for
short
term
and
intermediate
term
occupational
and
residential
postapplication
dermal
exposure.
Although
the
study
does
not
meet
guideline
requirements,
it
is
useful
for
risk
assessment
for
the
following
reasons:
1)
in
all
oral
studies
in
which
cholinesterase
was
measured,
it
was
the
most
sensitive
endpoint;
therefore,
other
guideline
parameters
would
most
likely
not
establish
a
lower
LOAEL;
2)
plasma
cholinesterase
was
not
measured;
however,
in
all
the
oral
studies
in
rats,
all
three
compartments
(plasma,
RBC
and
brain)
were
affected
at
the
same
dose
level.
Therefore,
it
is
likely
that
plasma
cholinesterase
would
not
have
been
inhibited
at
a
lower
level,
especially
given
the
minimal
effects
on
RBC
and
brain
cholinesterase.
MRID
45630602
In
a
non
guideline
four
week
dermal
toxicity
study
(MRID
45630602),
Sevin®
XLR
Plus
(44.82%
a.
i.,
Lot
60618902)
was
applied
to
the
shaved
skin
of
8
Crl:
CD
(SD)
IGS
BR
rats/
sex/
dose
at
dose
levels
of
0,
20,
50
or
100
mcL/
kg
bw/
day
(0,
9.6,
24
or
48
mg/
kg/
day),
6
hours/
day
for
5
days/
week
during
a
4
week
period.
The
parameters
measured
included
the
following:
clinical
observations,
body
weight,
body
weight
gain,
food
consumption,
RBC
cholinesterase
and
signs
of
dermal
irritation.
There
were
no
treatment
related
effects
on
clinical
observations
or
body
weight
or
evidence
of
dermal
irritation.
Females
treated
at
100
mcL/
kg/
day
gained
167%,
65%,
144%
and
40%
of
control
values
for
Days
3
to
5,
5
to
12,
12
to
19
and
19
to
26,
respectively.
Overall
(Days
3
to
26)
body
weight
gain
was
not
affected.
It
is
difficult
to
determine
if
there
was
a
treatment
related
effect
immediately
after
dosing
as
the
first
body
weight
measurement
was
not
done
until
Day
5
of
dosing.
Although
not
statistically
significant,
there
does
appear
to
be
a
treatment
related
decrease
on
the
body
weight
gain
(Days
5
to
12)
of
females
treated
at
100
mcL/
kg/
day.
RBC
cholinesterase
was
measured
before
dosing
on
Week
1
and
on
Days
1,
8,
15
and
22.
There
was
no
evidence
of
a
treatment
related
effect
at
these
time
periods.
Measurements
were
also
performed
within
1
hour
after
test
material
removal
on
Days
5,
12,
19,
and
26.
In
males,
the
only
statistically
significant
difference
from
control
values
was
on
Day
26
in
the
animals
dosed
at
50
mcL/
kg/
day;
the
decrease
was
only
8%.
Although
not
statistically
significant,
the
RBC
cholinesterase
on
Day
12
in
males
treated
at
100
mcL/
kg/
day
was
decreased
by
10%.
In
females
treated
at
100
mcL/
kg/
day,
values
were
significantly
decreased
on
Day
5
(12%),
Day
12
(12%)
and
non
significantly
decreased
on
Days
19
(5%)
and
Day
26
(7%).
There
were
also
significant
decreases
in
the
50
mcL/
kg/
day
females
on
Days
19
(9%)
and
26
(14%)
and
in
the
20
mg/
kg/
day
group
on
Day
26
(10%).
Although
statistically
significant,
the
RBC
cholinesterase
decreases
are
not
judged
to
be
toxicologically
significant
due
to
the
small
magnitude
of
the
effect
and
the
lack
of
a
dose
response
on
Days
19
and
26.
The
systemic
LOAEL
in
females
was
100
mcL/
kg/
day
(48
mg/
kg/
day)
based
on
decreased
body
weight
gain.
The
systemic
NOAEL
was
50
mcL/
kg/
day
(24
mg/
kg/
day).
The
systemic
LOAEL
in
males
was
not
established.
The
systemic
NOAEL
was
100
mcL/
kg/
day
(48
mg/
kg/
day).
The
dermal
LOAEL
was
not
established.
The
dermal
NOAEL
was
100
mcL/
kg/
day
(48
mg/
kg/
day).
This
4
week
dermal
toxicity
study
in
the
rat
is
unacceptable
(
non
guideline).
The
study
was
intended
for
use
in
the
short
term
and
intermediate
term
occupational
and
residential
handler
risk
assessments
for
11
the
liquid
formulations
of
carbaryl.
It
is
considered
unacceptable
and
not
upgradeable
because
RBC
cholinesterase
results
were
inconsistent
and
plasma
and
brain
cholinesterase
were
not
measured.
In
another
dermal
toxicity
study
(MRID
45630601),
brain
cholinesterase
inhibition
was
the
most
sensitive
and
reliable
endpoint.
Determination
of
cholinesterase
inhibition
in
all
three
compartments
would
have
helped
define
the
effect
level.
MRID
45630603
In
a
non
guideline
four
week
dermal
toxicity
study
(MRID
45630603),
Sevin®
80S
(80.07%
a.
i.,
Lot
C8I168025A)
was
applied
to
the
shaved
skin
of
8
Crl:
CD
(SD)
IGS
BR
rats/
sex/
dose
at
dose
levels
of
0,
20,
50
or
100
mg/
kg
bw/
day,
6
hours/
day
for
5
days/
week
during
a
4
week
period.
The
parameters
measured
included
the
following:
clinical
observations,
body
weight,
body
weight
gain,
food
consumption,
RBC
cholinesterase
and
signs
of
dermal
irritation.
There
was
no
treatment
related
effect
on
mortality,
clinical
observations,
body
weight
or
dermal
irritation.
Body
weight
gain
(relative
to
control
values)
in
the
100
mg/
kg/
day
males
was
highly
variable
between
time
periods.
There
were
non
significant
decreases
of
15%
and
20%
on
Days
3
to
5
and
19
to
26,
respectively
but
increases
of
9%
and
53%
were
observed
on
Days
5
to
12
and
12
to
19,
respectively.
Since
body
weight
was
not
measured
at
treatment
initiation,
it
is
difficult
to
determine
if
there
was
an
effect
during
the
first
time
period.
However,
food
consumption
was
significantly
decreased
by
12%
on
Days
1
to
5
in
this
group,
which
correlates
with
an
initial
treatment
related
effect.
Therefore,
the
decrease
in
body
weight
gain
in
the
100
mg/
kg/
day
males
is
considered
treatment
related.
RBC
cholinesterase
was
measured
before
dosing
on
Week
1
and
on
Days
1,
8,
15
and
22.
Statistically
significant
decreases
were
observed
in
the
50
and
100
mg/
kg/
day
females
on
Day
8
(10%
and
12%,
respectively).
These
effects
are
not
considered
toxicologically
significant
given
the
inconsistency
of
the
findings.
Measurements
were
also
performed
within
1
hour
after
test
material
removal
on
Days
5,
12,
19,
and
26.
In
males,
statistically
significant
decreases
were
observed
in
animals
treated
at
50
mg/
kg/
day
on
Days
12
(10%),
19
(13%)
and
26
(8%).
In
males
treated
at
100
mg/
kg/
day,
there
were
significant
decreases
on
Days
12
(20%),
19
(19%)
and
26
(19%).
Although
not
statistically
significant,
there
was
also
a
12%
decrease
on
Day
5
in
this
group.
In
females,
statistically
significant
decreases
were
observed
in
animals
treated
at
50
mg/
kg/
day
on
Days
12
(16%)
and
19
(12%).
Using
the
repeated
measures
ANOVA
test,
there
was
also
a
significant
decrease
on
Day
5
(12%)
in
this
group.
In
females
at
100
mg/
kg/
day,
there
were
significant
decreases
on
Days
12
(18%)
and
19
(15%)
and
Day
26
(15%).
The
systemic
LOAEL
is
50
mg/
kg/
day
based
on
statistically
significant
decreases
in
RBC
cholinesterase
in
males
and
females.
The
systemic
NOAEL
is
20
mg/
kg/
day.
The
dermal
LOAEL
was
not
established.
The
dermal
NOAEL
was
100
mg/
kg/
day.
This
4
week
dermal
toxicity
study
in
the
rat
is
unacceptable
(
non
guideline).
The
study
was
intended
for
use
in
the
short
term
and
intermediate
term
occupational
and
residential
handler
risk
assessments
for
the
solid
formulations
of
carbaryl.
It
is
considered
unacceptable
and
not
upgradeable
because
only
RBC
cholinesterase
was
measured.
In
the
dermal
toxicity
study
with
the
technical
chemical
(MRID
45630601),
brain
cholinesterase
inhibition
was
the
most
sensitive
and
reliable
endpoint.
While
this
study
does
support
the
RBC
cholinesterase
effects
in
MRID
45630601,
the
lack
of
plasma
and
brain
cholinesterase
12
measurements
makes
the
study
unacceptable
for
use
in
risk
assessment.
4.3
Prenatal
Developmental
Toxicity
Adequacy
of
data
base
for
Prenatal
Developmental
Toxicity:
The
data
base
for
prenatal
developmental
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
There
are
acceptable
prenatal
developmental
toxicity
studies
in
the
rat
and
rabbit.
There
was
no
evidence
of
increased
fetal
susceptibility
in
these
studies.
870.3700a
Prenatal
Developmental
Toxicity
Study
Rat
In
a
developmental
toxicity
study
(MRID
44732901),
Carbaryl
(99%
a.
i.)
in
an
aqueous
methylcellulose
suspension
was
administered
by
gavage
at
0,
1,
4,
and
30
mg/
kg/
day
to
pregnant
Crl:
CD
(SD)
BR
rats
(25/
dose)
during
gestation
days
(GDs)
6
through
20.
At
GD
21,
surviving
dams
were
sacrificed
and
necropsied.
There
were
no
treatment
related
gross
pathologic
findings
noted
in
any
of
the
dams.
There
were
no
differences
of
toxicological
concern
in
mortality,
pregnancy
rate,
numbers
of
corpora
lutea,
implantations,
viable
fetuses,
pre
and
post
implantation
losses,
placental
weights,
and
sex
ratio.
At
30
mg/
kg/
day,
at
least
one
occurrence
of
post
dosing
salivation
occurred
in
18/
25
of
the
dams
(vs
0/
25
controls).
This
clinical
sign
appeared
within
20
minutes
of
treatment,
disappeared
after
approximately
one
hour,
and
was
observed
from
GD
13
to
20.
There
were
no
deaths
and
no
other
treatment
related
clinical
signs.
Body
weights
of
the
high
dose
dams
were
3
8%
less
than
controls
throughout
the
study
(not
statistically
significant);
their
corrected
(for
gravid
uterine
weight)
body
weights
and
body
weight
gains
were
decreased
(p
0.01)
by
7
and
38%,
respectively.
Body
weight
gains
in
this
group
were
decreased
immediately
after
initiation
of
dosing
(GDs
6
9,
9
108%,
p
0.01)
and
throughout
treatment
(overall,
9
27%,
p
0.01).
Food
consumption
(g/
animal/
day)
was
decreased
throughout
the
treatment
period
(
10
17%,
p
0.01).
There
were
no
differences
of
toxicological
concern
observed
in
the
mid
and
low
dose
groups.
The
maternal
LOAEL
is
30
mg/
kg/
day
based
on
clinical
signs
of
toxicity,
decreased
body
weight
gains
and
food
consumption.
The
maternal
NOAEL
is
4
mg/
kg/
day.
In
the
high
dose
fetuses,
mean
fetal
body
weights
were
reduced
(
7
8%,
p
0.01).
Additionally,
the
following
were
observed
in
the
high
dose
male
and
female
fetuses:
(I)
an
increase
in
incomplete
ossification
of
the
5th
sternebra,
(ii)
unossified
7th
cervical
centrum,
(iii)
incomplete
ossification
of
7th
cervical
centrum,
and
(iv)
unossified
1st
metatarsal.
No
effects
on
fetal
viability
were
observed.
There
were
no
treatment
related
effects
in
developmental
parameters
observed
in
the
mid
and
low
dose
groups.
The
developmental
LOAEL
is
30
mg/
kg/
day
based
on
decreased
fetal
body
weights
and
increased
13
incomplete
ossification
of
multiple
bones.
The
developmental
NOAEL
is
4
mg/
kg/
day.
The
developmental
toxicity
study
in
the
rat
is
classified
as
acceptable
(§
83
3(
a))
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
in
the
rat.
870.3700b
Prenatal
Developmental
Toxicity
Study
Rabbit
In
a
developmental
toxicity
study
(MRID
44904202),
carbaryl
(99%
a.
i.)
in
an
aqueous
methylcellulose
suspension
was
administered
by
gavage
at
doses
of
0,
5,
50
or
150
mg/
kg/
day
to
pregnant
New
Zealand
White
rabbits
(22/
dose)
during
Gestation
Days
(GD)
6
29.
On
GD
25,
blood
was
collected
1
hour
postdosing
for
plasma
and
red
blood
cell
(RBC)
cholinesterase
(ChE)
measurements.
At
GD
30,
surviving
dams
were
sacrificed
and
necropsied;
fetuses
were
examined
for
evidence
of
developmental
effects.
Maternal
toxicity
at
150
mg/
kg/
day
was
observed
as
statistically
significant
decreased
body
weight
gain
as
compared
to
the
control
value
during
GD
6
9
(208%),
GD
6
29
(dosing
period,
53%),
GD
3
30
(33%)
and
gestation
(GD
0
GD
30,
38%).
Corrected
body
weight
change
was
also
decreased
at
this
dose
219.73
g
vs
81.86
g
in
the
control).
Although
not
statistically
significant,
the
body
weight
decreases
at
50
mg/
kg/
day
can
be
considered
biologically
significant
for
GD
6
9
(55%),
GD
6
29
(25%),
GD
3
30
(14%)
and
gestation
(14%).
There
was
no
treatment
related
effect
on
food
consumption.
Statistically
significantly
decreases
in
plasma
(46
68%)
and
RBC
(19
27%)
ChE
were
seen
at
50
and
150
mg/
kg/
day.
Maternal
LOAEL
=
50
mg/
kg/
day
based
on
decreased
body
weight
gain
and
decreased
plasma
and
RBC
ChE;
Maternal
NOAEL
=
5
mg/
kg/
day
The
only
evidence
of
developmental
toxicity
was
a
statistically
significant
decrease
in
fetal
body
weights
of
10%
(when
calculated
for
all
fetuses
or
individually
for
males
and
females)
at
150
mg/
kg/
day.
There
were
no
treatment
related
developmental
effects
observed
in
the
mid
and
low
dose
groups.
Developmental
Toxicity
LOAEL
is
150
mg/
kg/
day
based
on
decreased
fetal
weight.
Developmental
Toxicity
NOAEL
is
50
mg/
kg/
day
The
developmental
toxicity
study
in
the
rabbit
is
classified
as
acceptable/
guideline
and
does
satisfy
the
guideline
requirement
for
a
developmental
toxicity
study
in
the
rabbit.
4.4
Reproductive
Toxicity
Adequacy
of
data
base
for
Reproductive
Toxicity:
The
data
base
for
reproductive
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
In
the
reproduction
study
in
rats,
there
was
evidence
of
quantitative
susceptibility
of
offsprings.
The
LOAEL
for
parental
systemic
toxicity
was
based
on
decreased
body
weight,
weight
gain,
and
feed
consumption;
the
NOAEL
was
27
mg/
kg/
day
in
males
and
30
mg/
kg/
day
in
females.
In
the
offspring
the
LOAEL
was
based
on
increased
numbers
of
F2
pups
with
no
milk
in
the
stomach
and
decreased
pup
survival;
the
NOAEL
was
5
mg/
kg/
day
in
males
and
6
mg/
kg/
day
in
females.
Several
articles
have
been
published
in
the
open
literature
describing
effects
on
spermatogenesis
and
developmental/
reproduction
parameters
at
high
doses.
There
is
also
an
epidemiology
study
conducted
in
farmers
exposed
to
multiple
pesticides,
which
concluded
that
the
miscarriage
rate
was
14
increased
in
parents
where
the
father
was
exposed
to
carbaryl.
There
was
no
association
between
the
use
of
carbaryl
and
preterm
delivery,
small
for
gestational
age
or
altered
sex
ratio
measurements.
The
studies
and
articles
are
summarized
below.
870.3800
Reproduction
and
Fertility
Effects
Rat
In
a
two
generation
reproduction
study
(MRID
45448101),
carbaryl
(99.1%
a.
i,
Lot
No.
E1208008)
was
given
in
the
diet
to
groups
of
30
male
and
30
female
F0
and
F1
rats
(CD
®
[SD]
IGS
BR
(Sprague
Dawley))
at
concentrations
of
0,
75,
300,
or
1500
ppm.
The
dietary
concentrations
corresponded
to
doses
of
4.67,
31.34,
and
92.43
mg/
kg/
day
for
F0
males;
0,
5.56,
36.32,
and
110.78
mg/
kg/
day
for
F0
females;
0,
5.79,
23.49,
and
124.33
mg/
kg/
day
for
F1
males;
and
0,
6.41,
26.91,
and
135.54
mg/
kg/
day
for
F1
females
averaged
over
the
premating
period.
Each
group
received
treated
or
control
diet
continuously
for
70
days
prior
to
mating
and
during
mating,
gestation,
and
lactation
of
one
litter
per
generation.
F1
pups
selected
to
parent
the
F2
generation
were
weaned
onto
the
same
food
as
their
parents.
Parental
males
were
sacrificed
after
delivery
of
their
litters
and
parental
females
were
sacrificed
after
weaning
of
their
litters.
No
treatment
related
deaths,
clinical
signs,
organ
weight
changes,
gross
lesions,
or
microscopic
lesions
were
observed
in
adult
rats
of
either
generation.
No
treatment
related
effects
were
observed
on
body
weights,
weight
gain,
feed
consumption,
or
food
efficiency
in
75
or
300
ppm
group
F0
or
F1
male
or
female
rats
at
any
time
during
the
study
including
the
gestation
and
lactation
periods
of
the
females.
F0
and
F1
male
and
female
rats
fed
the
1500
ppm
diet
weighed
significantly
(p<
0.01
or
<0.05)
less
and
gained
less
weight
during
the
premating
period.
The
F0
males
weighed
5
6%
less
than
controls
during
premating,
gained
14
23%
less
weight
during
three
weekly
intervals
up
to
day
45,
and
gained
9%
less
weight
over
the
entire
premating
period;
they
also
gained
8%
less
weight
than
controls
over
the
mating/
postmating
period.
The
F1
males
weighed
10
19%
less
than
controls
during
the
entire
study,
gained
16%
and
11%
less
weight
during
the
first
two
weekly
intervals,
and
gained
8%
less
weight
than
controls
averaged
over
the
entire
premating
period.
The
F0
females
weighed
4
5%
less
than
controls
during
the
first
42
days
of
premating,
gained
27%
less
weight
during
the
first
week,
and
7%
(N.
S.)
less
averaged
over
the
entire
premating
period.
The
F1
females
weighed
8
22%
less
than
controls
throughout
premating
and
gained
9%
less
weight
during
the
first
week;
weight
gain
for
the
remaining
weekly
intervals
and
for
the
entire
premating
period
was
similar
to
that
of
controls.
Food
consumption
and
food
efficiency
for
F0
and
F1
rats
followed
patterns
similar
to
that
of
body
weight
and
weight
gain;
the
largest
difference
between
the
1500
ppm
groups
and
controls
occurred
during
the
early
part
of
the
premating
period.
When
averaged
over
the
entire
premating
period,
F0
and
F1
males
consumed
6
7%
less
food
than
control
and
had
food
efficiency
values
similar
to
those
of
the
controls.
Feed
consumption
and
food
efficiency
for
the
F0
females
were
similar
to
those
of
the
control
group,
whereas
F1
females
consumed
9%
(p<
0.01)
less
feed
and
had
a
food
efficiency
value
10%
(p<
0.01)
greater
than
that
of
controls.
F0
and
F1
females
in
the
1500
ppm
group
weighed
less
and
gained
less
weight
than
controls
during
gestation,
with
the
effect
being
greater
in
the
F1
females.
During
lactation
weight
gain
was
markedly
reduced
in
F1
females
during
the
first
4
days,
but
was
greater
than
that
of
controls
averaged
over
the
entire
lactation
period.
The
lowest
observed
effect
level
(LOAEL)
for
parental
systemic
toxicity
is
1500
ppm
(92.43
124.33
mg/
kg/
day
for
males
and
110.78
135.54
mg/
kg/
day
for
females)
based
on
decreased
body
weight,
15
weight
gain,
and
feed
consumption.
The
no
observed
adverse
effect
(NOAEL)
level
is
300
ppm
(23.49
31.34
mg/
kg/
day
for
males
and
26.91
36.32
mg/
kg/
day
for
females).
No
treatment
related
effects
were
observed
on
the
estrous
cycle
of
either
F0
or
F1
females
at
any
dose
level
or
on
percent
motile
sperm,
sperm
count,
percent
progressively
motile
sperm,
epididymal
sperm
count,
spermatid
head
count,
daily
sperm
production,
or
efficiency
of
daily
sperm
production
in
F0
or
F1
males
at
any
dose
level.
There
was
a
dose
related
increase
in
the
percentage
of
abnormal
sperm
in
the
treated
males
but
no
statistical
significance
at
any
dose
level.
No
treatment
related
gross
or
microscopic
effects
were
observed
in
male
or
female
rats
of
either
generation.
No
treatment
related
effects
were
observed
on
any
parameter
of
reproductive
performance
including,
mating
and
fertility
indexes,
gestation
index,
pregnancy
index,
precoital
duration,
gestation
length,
or
number
of
females
producing
live
litters.
The
LOAEL
for
reproductive
toxicity
could
not
be
established
because
no
effects
were
observed
at
any
dose
level;
therefore,
the
NOAEL
is
$
1500
ppm
(92.43
124.33
mg/
kg/
day
for
males
and
110.78
135.54
mg/
kg/
day
for
females).
No
treatment
related
effects
were
observed
on
implantation
sites/
litter,
number
of
live
pups
born/
litter,
number
of
dead
pups
born/
litter,
live
birth
index,
sex
ratio,
clinical
signs,
or
organ
weight
or
necropsy
findings
in
pups
surviving
to
21
days.
Pup
survival
was
decreased
at
300
and
1500
ppm
for
both
generations.
Increased
number
of
deaths
in
the
F2
generation
males
and
females
resulted
in
an
18
19%
decrease
in
mean
litter
size
on
postnatal
day
4
(p<
0.01
or
<0.05)
and
decreased
viability
and
lactation
indexes
at
1500
ppm.
A
large
number
of
pups
that
died
had
no
milk
in
their
stomachs.
In
addition,
pup
weight/
litter
and
pup
weight
gain
in
the
1500
ppm
group
pups
were
reduced
for
both
generations
starting
with
postnatal
day
4
(11
15%
for
F1
and
13
23%
for
F2
pups);
body
weight
gain
was
reduced
throughout
lactation
with
the
greatest
effect
occurring
during
the
first
7
days
for
F1
pups
and
the
first
14
days
for
F2
pups.
Sexual
maturation
was
delayed
in
1500
ppm
group
F1
offspring
as
evidenced
by
delayed
balanopreputial
separation
in
the
males
(+
2.1
days)
and
vaginal
patency
in
the
females
(+
1.4
days).
The
differences
remained
statistically
significant
after
adjustment
for
body
weight
decreases.
Anogenital
distance
was
significantly
reduced
in
F2
male
pups
in
the
1500
ppm
group,
but
not
when
the
distance
was
adjusted
for
body
weight.
The
LOAEL
for
offspring
toxicity
was
300
ppm
(23.49
31.34
mg/
kg/
day
for
males
and
26.91
36.32
mg/
kg/
day
for
females)
based
on
increased
numbers
of
F2
pups
with
no
milk
in
the
stomach
and
decreased
pup
survival.
The
NOAEL
is
75
ppm
(4.67
5.79
mg/
kg/
day
for
males
and
5.56
6.41
mg/
kg/
day
for
females).
This
study
is
Acceptable/
Guideline
and
satisfies
the
guideline
requirement
for
a
two
generation
reproductive
study
(OPPTS
870.3800;
OECD
416)
in
the
rat.
Literature
Articles
In
a
1996
study
in
the
open
literature,
carbaryl
was
administered
to
four
groups
of
6
young
and
6
adult
1
Pant
N,
Shankar
R,
Srivastava
SP
(1996).
Spermatotoxic
effects
of
carbaryl
in
rats.
Human
Exp
Toxicol
15(
9);
736
38.
2
Pant
N,
Srivastava
SC,
Prasad
AK,
Shankar
R,
Srivastava
SP
(1995).
Effects
of
Carbaryl
on
the
Rat's
Male
Reproductive
System.
Vet
Human
Toxicol
37(
5):
421
425.
16
Druckery
albino
rats
per
group
at
doses
of
0,
25,
50
or
100
mg/
kg/
day
for
60
days.
1
Body
weight
was
recorded
at
initiation
and
completion
of
the
study.
On
the
61st
day,
the
animals
were
sacrificed
and
the
testes,
epididymides,
seminal
vesicles,
ventral
prostrate
and
coagulating
glands
were
weighed.
Epididymal
sperm
were
used
for
sperm
counts
and
examination
of
motility
and
morphology.
No
overt
toxicity
or
mortality
was
observed.
There
were
dose
related
effects
on
body
weight
for
the
50
and
100
mg/
kg/
day
groups.
The
absolute
weights
of
the
testes,
epididymides,
seminal
vesicle,
ventral
prostrate
and
coagulating
glands
were
significantly
decreased
at
100
mg/
kg/
day
for
young
rats.
The
relative
organ
weights
were
not
affected
at
any
doses.
The
organ
weights
were
not
affected
in
adult
animals.
Young
rats
receiving
carbaryl
50
mg/
kg/
day
had
a
24.4%
and
25%
decrease
in
sperm
motility
and
sperm
count,
respectively;
the
changes
at
100
mg/
kg/
day
were
42.9%
and
37.5%,
respectively.
Adults
receiving
the
50
mg/
kg/
day
dose
had
a
15.1%
and
12.5%
reduction
in
sperm
motility
and
count,
respectively;
the
changes
at
100
mg/
kg/
day
were
26.4%
and
25%,
respectively.
The
percentage
of
young
rats
with
abnormal
sperm
was
19.8%
and
33.7%
at
50
and
100
mg/
kg/
day,
respectively.
In
adults,
the
percentages
were
16.1%
and
23.1%
for
the
respective
doses.
In
another
study
from
this
laboratory,
three
groups
of
8
male
Wistar
rats
per
group
were
administered
carbaryl
by
gavage
at
doses
of
0,
50
or
100
mg/
kg/
day
for
90
days.
2
Body
weight
was
measured
periodically
throughout
the
study.
On
the
91st
day,
the
animals
were
sacrificed
and
the
male
reproductive
glands
were
weighed.
One
testis
from
each
animal
was
preserved
for
histopathology
and
the
other
was
homogenized
for
testicular
enzyme
assay.
Epididymal
sperm
were
used
for
sperm
counts
and
examination
of
motility
and
morphology.
No
clinical
signs
of
toxicity
were
observed,
except
for
lethargy.
Body
weights
were
decreased
in
the
100
mg/
kg/
day
group
after
60
days.
There
were
no
changes
in
the
weights
of
reproductive
organs.
There
were
significant
changes
in
the
testicular
enzymes
of
the
100
mg/
kg/
day
group:
decreases
in
SDH
and
G6PDH
and
increases
in
GGT
and
LDH.
At
both
doses,
there
were
significant
decreases
in
the
total
epididymal
sperm
count,
percent
sperm
motility
and
increases
in
the
percent
with
morphological
abnormalities
in
head,
neck
and
tail.
At
50
mg/
kg/
day,
the
testes
had
slight
to
moderate
congestion
and
edema.
A
few
tubules
showed
moderately
depressed
spermatogenesis
and
loss
of
sperm.
There
was
moderate
atrophy
of
seminiferous
tubules
with
prominent
interstitial
spaces
in
the
center
of
the
testes,
but
the
Leydig
cells
were
intact.
At
100
mg/
kg/
day,
there
were
increases
in
the
intensity
of
congestion
and
the
edematous
reaction
was
seen
both
peripherally
and
in
the
central
region.
Most
of
the
seminiferous
tubules
had
disturbed
spermatogenesis
as
well
as
accumulations
of
cellular
masses
in
their
lumens.
In
a
study
conducted
at
EPA's
Health
Effects
Research
Laboratory,
16
pregnant
Fischer
344
rats
were
administered
carbaryl
by
gavage
on
gestation
days
(GD)
6
19
at
doses
of
78
or
104
mg/
kg/
day;
21
3
Narotsky
MG,
Kavlock
RJ
(1995).
A
Multidisciplinary
Approach
to
Toxicological
Screening:
II.
Developmental
Toxicity.
Journal
of
Toxicology
and
Environmental
Health
45:
145
171.
4
Savitz
DA,
Arbuckle
T,
Kaczor
D,
Curtis
KM
(1997).
Male
Pesticide
Exposure
and
Pregnancy
Outcome.
Am
J
Epidemiol
146(
12):
1025
36.
17
control
animals
were
used.
3
The
high
dose,
selected
to
produce
overt
maternal
toxicity,
was
based
on
the
results
of
a
14
day
repeated
dose
study
in
nonpregnant
female
rats.
The
low
dose
was
75%
of
the
high
dose.
Maternal
body
weights
were
determined
on
GD
6,
8,
10,
13,
16
and
20.
All
rats
were
examined
periodically
for
clinical
signs
of
toxicity.
Pups
in
each
litter
were
examined
and
counted
on
postnatal
day
(PD)
1,
3,
and
6
and
weighed
collectively
on
PD
1
and
6.
After
the
final
litter
examination,
the
dams
were
killed
and
uterine
implantation
sites
counted.
Females
that
did
not
deliver
by
GD
24
were
killed
and
their
uteri
examined
for
pregnancy
status.
Clinical
signs
of
toxicity
observed
in
the
dams
included
tremors,
motor
depression,
and
lacrimation,
usually
during
the
first
three
days
of
treatment.
Jaw
clonus
was
observed
throughout
the
treatment
period.
(The
article
does
not
indicate
if
clinical
signs
were
observed
at
both
doses.)
Marked
weight
loss
was
observed
early
in
treatment.
Over
the
entire
treatment
period,
carbaryl
produced
extrauterine
weight
loss
at
the
high
dose
and
reduced
weight
gains
at
the
low
dose.
There
was
increased
prenatal
mortality
at
the
high
dose;
this
effect
was
attributed
to
two
(15%)
fully
resorbed
litters
in
this
group.
In
addition,
high
dose
pup
weights
were
significantly
reduced
on
PD
1.
The
PD
1
pup
weights
in
the
low
dose
and
the
PD
6
pup
weights
in
both
carbaryl
exposed
groups
were
also
significantly
reduced,
but
only
when
analyzed
using
the
number
of
live
pups
on
PD
1
as
the
covariate.
In
a
recent
epidemiology
study,
the
effects
of
exposure
of
male
farmers
in
Ontario,
Canada,
to
agricultural
pesticides
and
pregnancy
outcome
was
investigated.
4
Miscarriage
risk
was
not
associated
with
participation
in
farm
activities
for
all
types
of
chemical
applications,
but
was
increased
in
combination
with
reported
use
of
thiocarbamates,
carbaryl
and
unclassified
pesticides
on
the
farm
(Odds
ratio
=
1.9,
95%
C.
I.
1.1
3.1).
There
was
no
association
between
use
of
carbaryl
and
preterm
delivery,
small
for
gestational
age
or
altered
sex
ratio
measurements.
4.5
Chronic
Toxicity
Adequacy
of
data
base
for
chronic
toxicity:
The
data
base
for
chronic
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
In
the
chronic
toxicity
study
in
dogs,
at
the
lowest
dose
tested,
plasma
ChEI
in
females
and
brain
ChEI
in
males
were
observed.
In
a
5
week
study
to
establish
the
ChEI
NOAEL,
plasma
ChEI
was
the
basis
for
setting
the
NOAEL/
LOAEL.
870.4100b
Chronic
Toxicity
Dog
In
a
chronic
toxicity
study
(MRID
No.
40166701),
Carbaryl
(99%)
was
administered
in
the
diet
to
6
beagle
dogs/
sex/
group
at
doses
of
0,
125,
400
or
1250
ppm
for
one
year.
Nominal
doses
were
3.1,
10
and
31.3
mg/
kg/
day.
There
were
no
deaths
during
the
study.
With
the
1250
ppm
females,
there
was
an
increased
incidence
of
clinical
signs
of
toxicity,
including
emesis,
lacrimation,
salivation
and
tremors.
Mean
body
weight
gain
18
was
decreased
(50%)
in
the
1250
ppm
females
for
weeks
0
6.
Mean
food
consumption
was
decreased
(16
24%,
not
statistically
significant)
in
the
1250
ppm
females
at
multiple
time
periods
during
the
study.
No
treatment
related
ophthalmoscopic
changes
were
observed.
There
was
a
statistically
significant
increase
in
white
blood
cell
and
segmented
neutrophil
counts
at
some
of
the
testing
intervals
for
the
1250
ppm
group
males.
Albumin
levels
were
significantly
decreased
(9
11%)
at
all
of
the
testing
periods
in
the
1250
ppm
females.
Plasma
cholinesterase
(ChE)
levels
in
males
were
significantly
decreased
in
the
400
ppm
(30
36%
9
)
and
1250
ppm
(58
66%
9
)
groups
at
all
testing
intervals
(weeks
5,
13,
26
and
52).
Plasma
ChE
levels
in
females
were
significantly
decreased
at
most
intervals
in
the
125
ppm
group
(12
23%
9
),
400
ppm
group
(9
31%
9
)
and
1250
ppm
group
(47
60
).
RBC
ChE
levels
in
males
were
significantly
decreased
in
the
400
ppm
group
(23
28%
9
at
weeks
5
and
13)
and
1250
ppm
group
(46
56%
9
for
all
intervals).
RBC
ChE
levels
in
females
were
significantly
decreased
in
the
400
ppm
group
(29
34%
9
at
weeks
5,
13
and
26)
and
1250
ppm
(29
38%
9
for
all
intervals).
Brain
ChE
in
males
was
not
statistically
significantly
decreased
but
biologically
decreased
in
the
400
ppm
group
(32%
9
)
and
1250
ppm
group
(25%
9
).
Brain
ChE
in
females
was
significantly
decreased
(20
36%
9
)
in
all
the
groups.
No
treatment
related
effects
were
seen
in
urinalysis
parameters.
At
necropsy,
there
was
a
statistically
significant
increase
in
the
absolute
weight
of
the
liver/
gall
bladder
in
the
1250
ppm
group
males.
Relative
and
liver
to
brain
weights
were
also
increased
but
not
significantly.
There
was
a
dose
related
decrease
in
the
absolute,
relative
and
organ
to
brain
weights
of
the
pituitary
in
males,
although
none
of
the
changes
was
statistically
significant.
There
was
also
a
significant
decrease
in
the
relative
weight
of
the
thyroid
in
this
group.
However,
since
there
were
no
accompanying
microscopic
changes
in
these
organs,
the
toxicological
significance
of
these
organ
weight
effects
is
questionable.
The
LOAEL
for
systemic
toxicity
was
1250
ppm
(31.3
mg/
kg/
day)
based
on
an
increased
incidence
of
clinical
signs
(females),
decreased
body
weight
and
food
consumption
(females)
and
alterations
in
clinical
pathology
parameters
(both
sexes);
NOAEL
was
400
ppm
(10
mg/
kg/
day).
The
LOAEL
for
plasma
cholinesterase
inhibition
was
125
ppm
(3.1
mg/
kg/
day)
for
females;
a
NOAEL
was
not
established.
The
LOAEL
for
plasma
cholinesterase
inhibition
was
400
ppm
(10
mg/
kg/
day)
for
males;
the
NOAEL
was
125
ppm
(3.1
mg/
kg/
day).
The
LOAEL
for
RBC
cholinesterase
inhibition
was
400
ppm
(10
mg/
kg/
day)
for
males
and
females;
the
NOAEL
was
125
ppm
(3.1
mg/
kg/
day).
The
LOAEL
for
brain
cholinesterase
inhibition
was
125
ppm
(3.1
mg/
kg/
day)
for
females;
a
NOAEL
was
not
established.
The
LOAEL
for
brain
cholinesterase
inhibition
was
400
ppm
(10
mg/
kg/
day)
for
males;
the
NOAEL
was
125
ppm
(3.1
mg/
kg/
day).
In
a
five
week
study
(MRID
#
42022801),
Carbaryl
(99.3%
a.
i.)
was
administered
in
the
diet
to
six
beagles/
sex/
group
at
doses
of
0,
20,
45
or
125
ppm.
Actual
mg/
kg/
day
doses
for
males
were
0,
0.59,
1.43
and
3.83
mg/
kg/
day,
respectively;
doses
for
females
were
0,
0.64,
1.54
and
4.11
mg/
kg/
day,
respectively.
The
following
parameters
were
measured:
clinical
observations,
body
weights,
food
consumption,
ophthalmoscopic
examinations,
plasma
and
RBC
cholinesterase
(at
days
11,
8
and
5
pretest
and
then
days
14
and
32
of
the
study),
brain
cholinesterase
(at
termination)
and
gross
necropsies.
19
This
study
was
conducted
to
complete
the
information
needed
to
satisfy
the
chronic
toxicity
study
requirement
in
nonrodent
species.
There
were
no
deaths
or
treatment
related
clinical
signs
of
toxicity.
There
were
no
treatment
related
effects
on
body
weights,
food
consumption
or
ophthalmoscopic
examinations.
In
males,
there
was
a
statistically
and
biologically
significant
decrease
in
plasma
cholinesterase
for
the
125
ppm
(22%
9
)
group.
The
LOAEL
for
systemic
toxicity
and
for
RBC
and
brain
cholinesterase
inhibition
was
>125
ppm
(males:
3.83
mg/
kg/
day;
females:
4.11
mg/
kg/
day);
the
NOAEL
was
$
125
ppm.
The
LOAEL
for
plasma
cholinesterase
inhibition
for
males
was
125
ppm;
the
NOAEL
was
45
ppm
(1.43
mg/
kg/
day).
The
LOAEL
for
cholinesterase
inhibition
for
females
was
>125
ppm;
the
NOAEL
was
$
125
ppm.
Together,
these
studies
are
acceptable
and
satisfy
the
guideline
requirements
for
a
chronic
toxicity
study
in
a
nonrodent
species
(83
1).
4.6
Carcinogenicity
Adequacy
of
data
base
for
Carcinogenicity:
The
data
base
for
carcinogenicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
In
both
the
rat
combined
chronic
toxicity/
carcinogenicity
study
and
the
mouse
carcinogenicity
study,
there
was
an
increase
incidence
of
tumors,
including
kidney,
liver
and
vascular
tumors,
in
the
treated
groups.
However,
the
highest
dose
in
both
studies
was
considered
excessive
based
on
evidence
of
severe
toxicity.
In
addition
to
the
required
carcinogenicity
studies
in
mice
and
rats,
the
registrant
submitted
a
special
study
in
genetically
modified
mice.
Carbaryl
was
administered
in
the
diet
to
heterozygous
p53
deficient
(knockout)
male
mice
at
concentrations
of
up
to
4000
ppm
(716.6
mg/
kg/
day)
for
six
months.
There
was
no
evidence
of
neoplastic
or
preneoplastic
changes
in
the
vascular
tissues
of
any
organ.
A
model
validation
study
demonstrated
that
vascular
tumors
occur
in
heterozygous
p53
deficient
mice
within
six
months
of
administration
of
a
known
genotoxic
carcinogen
(urethane).
The
CARC
(11/
7/
01)
considered
all
the
available
toxicity
data
and
concluded
that
the
malignant
vascular
tumors
(hemangiosarcomas)
in
male
mice
occurred
at
doses
which
were
adequate
and
not
excessive.
In
females
these
tumors
occurred
only
at
the
highest
dose
which
was
excessively
toxic.
Nevertheless,
the
findings
in
female
mice
were
supportive
of
vascular
tumors
in
male
mice.
The
CARC
classified
carbaryl
as
"Likely
to
be
carcinogenic
in
humans"
based
on
an
increased
incidence
of
hemangiosarcomas
in
male
mice
at
all
doses
tested
(100,
1000
and
8000
ppm).
The
Q1*,
based
on
the
CD
1
mouse
dietary
study
with
¾
Interspecies
Scaling
Factor,
is
8.75
x
10
4
(mg/
kg/
day)
1
in
human
equivalents.
870.4200b
Carcinogenicity
(feeding)
Mouse
In
a
carcinogenicity
study
(MRID
No.
42786901),
80
CD
1®
mice/
sex/
group
were
administered
technical
Carbaryl
(99.3%
a.
i.)
in
the
diet
at
dosages
of
either
0,
100,
1000
or
8000
ppm
for
104
weeks
(males:
0,
14.73,
145.99
and
1248.93
mg/
kg/
day;
females:
0,
18.11,
180.86
and
1440.62
mg/
kg/
day,
20
respectively.)
Four
males
in
the
8000
ppm
group
died
during
the
first
week
of
treatment;
the
cause
of
death
was
not
determined.
Survival
rates
were
not
affected
by
treatment.
Animals
in
the
8000
ppm
group,
especially
the
females,
developed
clinical
signs
of
toxicity,
including
hunched
posture,
thin
and
languid
appearance,
squinted
and
opaque
eyes,
urine
stains,
redness
to
various
body
areas,
rough
hair
coat,
soft
feces
and
low
body
temperature.
Mean
body
weights
were
statistically
significantly
decreased
for
the
8000
ppm
males
and
females
for
the
majority
of
the
study
(males
9
13%;
females
5
14%).
Mean
body
weight
gain
for
the
8000
ppm
males
and
females
was
decreased
throughout
the
study
(males
23
38%;
females
10
32%).
Mean
food
consumption
was
statistically
significantly
decreased
in
the
8000
ppm
females
(7
10%).
Hematology
parameters,
including
RBC,
hemoglobin
and
hematocrit,
were
statistically
significantly
decreased
in
the
8000
ppm
females
at
week
53
and
8000
ppm
group
males
at
week
105.
Total
leukocyte
count
and
counts
of
lymphocytes
and
eosinophils
were
significantly
increased
in
the
8000
ppm
group
females
at
week
53.
Platelet
counts
were
significantly
increased
in
this
group
at
week
105.
RBC
cholinesterase
(ChE)
was
statistically
significantly
decreased
in
the
1000
ppm
(23%
9
)
and
8000
ppm
(30%
9
)
group
males
at
week
53.
RBC
ChE
was
decreased
in
the
8000
ppm
group
females
(24%
9
)
at
week
105,
although
the
change
was
not
statistically
significant.
Brain
ChE
was
statistically
significantly
decreased
in
the
1000
and
8000
ppm
group
males
at
both
weeks
53
and
105
(13
18%
9
for
the
1000
ppm
group;
40
57%
9
for
the
8000
ppm
group)
and
in
the
8000
ppm
females
(34
47%
9
).
Brain
ChE
was
also
significantly
decreased
(13%
9
)
in
the
1000
ppm
group
females
at
week
53.
However,
the
percentage
decreases
from
the
control
level
were
less
than
20%
for
the
1000
ppm
group
males
and
females
at
both
weeks
53
and
105.
Therefore,
the
biological
significance
of
these
findings
is
questionable.
Plasma
ChE
values
were
not
affected
by
treatment.
There
were
no
treatment
related
macroscopic
effects
at
the
week
53
sacrifice,
however
at
the
week
105
sacrifice
the
incidence
of
opaque
eyes
was
increased
in
the
8000
ppm
group
(males:
1/
37
controls
vs.
4/
30;
females:
2/
34
controls
vs.
16/
32).
The
most
consistent
organ
weight
changes
at
both
necropsies
were
increased
relative
liver
and
kidney
weights.
On
microscopic
examination,
there
was
an
increased
incidence
of
chronic
progressive
nephropathy
in
the
1000
ppm
males
and
8000
ppm
males
and
females
at
the
interim
sacrifice.
The
severity
of
extramedullary
hematopoiesis
and
pigment
in
the
spleen
in
the
8000
ppm
males
and
females
was
increased
at
the
interim
sacrifice.
There
was
a
dose
related
increased
incidence
of
intracytoplasmic
protein
like
droplets
in
the
urinary
bladder
in
the
1000
and
8000
ppm
group
males
and
females
at
the
terminal
and
unscheduled
sacrifices.
The
incidence
of
animals
with
cataracts
was
increased,
but
not
dose
related,
in
the
8000
ppm
group
males
and
females.
The
study
demonstrated
that
Carbaryl
is
carcinogenic
in
mice
at
doses
of
100
ppm
(14.73
mg/
kg/
day)
and
higher
in
males
and
8000
ppm
(1440.62
mg/
kg/
day)
in
females.
There
was
an
increased
incidence
of
vascular
neoplasms
(hemangiomas
and
hemangiosarcomas)
in
all
treated
males
and
in
the
8000
ppm
group
females
at
the
terminal
and
unscheduled
necropsies
but
not
at
week
53.
Considering
all
animals,
there
was
an
increased
incidence
of
adenomas,
multiple
adenomas
and
carcinomas
of
the
kidney
in
the
8000
ppm
group
males.
The
incidence
of
hepatic
neoplasms
(adenomas,
carcinomas
and
one
hepatoblastoma)
was
increased
in
the
8000
ppm
group
females.
The
HED
CPRC
concluded
that
the
8000
ppm
dose
was
excessive
based
on
the
significantly
decreased
body
weight
gain
in
males
(33%)
and
females
(19%)
during
week
13,
a
significant
decrease
in
RBC
and
brain
cholinesterase
activity,
21
clinical
signs
of
toxicity
and
histopathological
changes
in
the
bladder,
kidneys
and
spleen
in
both
sexes.
The
systemic
LOAEL
was
1000
ppm
(M:
145.99
mg/
kg/
day;
F:
180.86
mg/
kg/
day)
based
on
an
increased
incidence
of
intracytoplasmic
droplets
in
the
superficial
epithelial
cells
of
the
urinary
bladder
in
males
and
females
and
chronic
progressive
nephropathy
in
males.
The
systemic
NOAEL
was
100
ppm
(M:
14.73
mg/
kg/
day;
F:
18.11
mg/
kg/
day).
The
RBC
cholinesterase
inhibition
LOAEL
in
males
was
1000
ppm
(23%
9
at
week
53);
the
NOAEL
was
100
ppm.
The
RBC
cholinesterase
inhibition
LOAEL
in
females
was
8000
ppm
(24%
9
at
week
105);
the
NOAEL
was
1000
ppm.
The
plasma
cholinesterase
inhibition
LOAEL
was
>8000
ppm
(M:
1248.93
mg/
kg/
day;
F:
1440.62
mg/
kg/
day);
the
NOAEL
was
$
8000
ppm.
The
brain
cholinesterase
inhibition
LOAEL
for
males
and
females
was
8000
ppm
(M:
40
57%
9
;
F:
34
47%
9
);
the
NOAEL
was
1000
ppm.
This
study
is
classified
as
Acceptable
and
satisfies
the
guidelines
for
a
carcinogenicity
study
in
mice
(§
83
2).
870.4300
Combined
Chronic
Toxicity/
Carcinogenicity
Study
rat
In
a
combined
carcinogenicity/
chronic
toxicity
study
(MRID
No.
42918801),
70
Sprague
Dawley
Crl:
CD®
BR
rats/
sex/
group
were
administered
technical
Carbaryl
(99%
a.
i.)
in
the
diet
at
dosages
of
either
0,
250,
1500
or
7500
ppm
for
104
weeks
(males:
0,
10.0,
60.2
and
349.5
mg/
kg/
day;
females:
0,
12.6,
78.6
and
484.6
mg/
kg/
day).
An
additional
10
animals/
sex/
dose
were
administered
the
same
doses
and
were
sacrificed
after
53
weeks.
Another
10
animals/
sex
from
the
control
and
high
dose
group
animals
were
sacrificed
at
week
57
after
switching
the
diet
of
the
high
dose
animals
to
control
feed
for
weeks
53
57
of
the
study.
There
was
no
treatment
related
effect
on
survival.
There
was
an
increased
incidence
of
clinical
signs
of
toxicity,
including
hunched
posture,
thin
appearance,
chromodacryorrhea
and
urine
stains
in
the
7500
ppm
group
males.
There
was
an
increased
incidence
of
alopecia
and
urine
strains
in
the
7500
ppm
group
females.
Statistically
significant
decreases
in
mean
body
weight
were
observed
in
the
7500
ppm
males
(24
35%)
and
females
(24
45%)
and
the
1500
ppm
females
(4
12%).
Mean
body
weight
gain
over
the
course
of
the
study
was
decreased
in
the
7500
ppm
males
(53%)
and
females
(69%).
There
was
a
18%
decrease
in
body
weight
gain
in
the
1500
ppm
females
for
the
week
0
104
period
only.
Food
consumption
in
the
7500
ppm
group
males
and
females
was
decreased
(4
16%
in
males;
11
21%
in
females)
during
the
study.
In
the
recovery
group,
rebound
in
food
consumption
and
body
weight
gain
was
seen,
but
mean
body
weight
was
still
decreased
23%
for
both
the
7500
ppm
males
and
females
at
week
57.
There
was
an
increased
incidence
of
unilateral
and
bilateral
cataracts
in
the
7500
ppm
males
and
females.
A
consistent
decrease
in
WBC
and
lymphocyte
count
in
the
7500
ppm
males
and
females
was
seen.
22
Alterations
in
clinical
chemistry
in
the
7500
ppm
males
and
females
included
significant
increases
in
cholesterol
and
BUN
and
significant
decreases
in
AST,
ALT
and
CPK.
Plasma
cholinesterase
was
decreased
in
the
7500
ppm
males
(27
42%)
and
females
(46
57%)
at
all
of
the
testing
intervals
(weeks
27,
53,
79
and
105),
however
all
of
the
changes
were
not
statistically
significant.
RBC
cholinesterase
was
decreased
in
the
7500
males
(19
37%)
and
females
(25
38%)
and
in
the
1500
ppm
males
(10
23%)
and
females
(12
26%)
at
most
of
the
testing
intervals.
At
weeks
53
and
105,
brain
cholinesterase
was
statistically
significantly
decreased
in
the
7500
ppm
males
(8
28%)
and
females
(22
31%).
In
the
recovery
group,
cholinesterase
values
had
returned
to
normal
levels
by
week
56.
There
was
a
slightly
increased
incidence
of
erythrocytes
in
the
urine
of
the
7500
ppm
males
and
occult
blood
in
the
7500
ppm
males
and
females.
An
increased
incidence
of
dark
urine
in
the
1500
ppm
females
and
in
the
7500
ppm
males
and
females
was
also
found.
There
were
no
treatment
related
macroscopic
findings
at
the
week
53
and
57
necropsies.
At
the
week
105
necropsy,
the
macroscopic
findings
at
an
increased
incidence
in
the
7500
ppm
males
and
females,
which
were
also
associated
with
microscopic
changes,
included
pale
areas
in
the
lungs
and
liver
and
urinary
bladder
masses.
A
decreased
absolute
weight
and
an
increased
relative
weight
of
the
kidneys,
lungs,
spleen
and
liver
were
found
in
the
7500
ppm
males
and
females.
At
the
week
53
necropsy,
there
were
slight
increases
in
the
incidence
of
microscopic
changes
in
the
kidney
and
liver
of
the
7500
ppm
males
and
females.
At
the
week
105
necropsy,
there
was
a
wide
variety
of
changes
in
multiple
organs
of
males
and
females
in
the
7500
ppm
group.
In
the
liver,
there
was
an
increased
incidence
in
the
following:
hepatocytic
hypertrophy
in
males
and
females;
and
eosinophilic
foci
and
pigment
in
females.
In
the
urinary
bladder,
there
was
an
increased
incidence
of
transitional
cell
hyperplasia,
squamous
metaplasia,
high
mitotic
index
and
atypia
in
males
and
females.
In
the
lung,
there
was
an
increased
incidence
of
focal
pneumonitis
and
foamy
macrophages
in
males
and
females.
In
the
kidney,
there
was
an
increased
incidence
of
transitional
cell
hyperplasia
in
males.
In
the
thyroid,
there
was
an
increased
incidence
of
follicular
cell
hypertrophy
in
males
and
females.
Degeneration
of
the
sciatic
nerve
and
skeletal
muscle
was
observed
at
an
increased
incidence
in
males
and
females.
The
study
demonstrated
that
Carbaryl
is
carcinogenic
in
male
and
female
rats
at
7500
ppm.
There
was
an
increased
incidence
of
liver
adenomas
in
females.
In
the
bladder,
there
was
an
increased
incidence
of
benign
transitional
cell
papilloma
and
transitional
cell
carcinomas
in
males
and
females.
One
transitional
cell
carcinoma
was
also
observed
in
the
kidney
of
a
male
rat.
In
the
thyroid,
the
incidence
of
benign
follicular
cell
adenomas
was
increased
in
males;
one
follicular
cell
carcinoma
was
also
seen
in
a
male.
The
HED
CPRC
evaluated
the
toxicity
data
on
Carbaryl
and
considered
7500
ppm
to
be
an
excessive
dose
based
on
the
following
findings:
1)
changes
in
body
weight
gain
during
week
13
for
males
and
females
by
40%
and
52%,
respectively,
as
compared
to
controls;
2)
decreased
food
efficiency;
3)
alterations
in
hematology
and
clinical
chemistry;
and
4)
decreases
in
plasma,
RBC
and
brain
cholinesterase
at
weeks
53
and
105.
The
systemic
LOAEL
was
1500
ppm
(78.6
mg/
kg/
day)
in
females
based
on
decreased
body
weight
and
body
weight
gain;
the
NOAEL
was
250
ppm
(12.6
mg/
kg/
day).
The
systemic
LOAEL
was
7500
ppm
(349.5
mg/
kg/
day)
in
males
based
on
an
increased
incidence
of
clinical
signs
of
toxicity,
decreases
in
23
body
weight,
body
weight
gain
and
food
consumption,
an
increased
incidence
of
cataracts,
alterations
in
clinical
pathology
parameters,
organ
weight
changes,
and
an
increased
incidence
of
nonneoplastic
microscopic
changes.
The
systemic
NOAEL
was
1500
ppm
(60.2
mg/
kg/
day)
in
males.
The
LOAEL
for
plasma
cholinesterase
inhibition
was
7500
ppm
in
males
(27
47%
decrease)
and
females
(46
57%
decrease);
the
NOAEL
was
1500
ppm.
The
LOAEL
for
RBC
cholinesterase
inhibition
was
1500
ppm
in
males
(10
23%
decrease)
and
females
(12
26%
decrease);
the
NOAEL
was
250
ppm.
The
LOAEL
for
brain
cholinesterase
inhibition
was
7500
ppm
in
males
(8
28%
decrease)
and
females
(22
31%
decrease);
the
NOAEL
was
1500
ppm.
This
study
is
classified
as
Acceptable
and
satisfies
the
guidelines
for
a
combined
carcinogenicity/
chronic
toxicity
feeding
study
in
rats
(83
5).
Carcinogenicity
and
Other
Studies
in
p53
Knockout
Mice
In
a
special,
non
guideline
study
(MRID
45281801,
45281802,
45236603),
heterozygous
p53
deficient
(knockout)
male
mice
(20/
group)
were
administered
carbaryl
in
the
diet
at
concentrations
of
0,
10,
30,
100,
300,
1000
and
4000
ppm
(approximately
0,
1.8,
5.2,
17.5,
51.2,
164.5
and
716.6
mg/
kg/
day,
respectively)
for
six
months.
The
doses
selected
for
this
study
were
based
on
two
28
day
studies
(MRID
45236603)
in
wild
type
mice
in
which
body
weight
decreases
were
observed
at
4000
and
8000
ppm
concentrations
of
carbaryl
in
the
diet.
A
validation
study
(MRID
45281802)
demonstrated
that
vascular
tumors
occur
in
heterozygous
p53
deficient
mice
within
6
months
of
administration
of
a
known
genotoxic
carcinogen
(urethane).
These
studies
were
conducted
to
demonstrate
that
carbaryl
is
a
non
genotoxic
carcinogen.
In
the
standard
mouse
carcinogenicity
study
(MRID
42786901)
at
dietary
concentrations
of
0,
100,
1000
or
8000
ppm,
there
was
an
increased
incidence
of
vascular
neoplasms
(hemangiomas
and
hemangiosarcomas)
in
all
treated
males
and
in
the
8000
ppm
group
females.
There
was
an
increased
incidence
of
adenomas,
multiple
adenomas
and
carcinomas
of
the
kidney
in
the
8000
ppm
group
males.
The
incidence
of
hepatic
neoplasms
(adenomas,
carcinomas
and
one
hepatoblastoma)
was
increased
in
the
8000
ppm
group
females.
At
meetings
on
October
27
and
December
8,
1993,
the
HED
Cancer
Peer
Review
Committee
concluded
that
the
8000
ppm
dose
was
excessive.
Therefore,
the
relevance
of
tumors
at
this
dose
was
questionable.
In
the
p53
knockout
mouse
study
with
carbaryl,
there
was
a
slight
decrease
in
body
weight
and
food
consumption
in
the
4000
ppm
group.
No
other
treatment
related
effects
were
observed,
except
globular
deposits
in
the
urinary
bladder
were
observed
in
a
high
proportion
of
the
mice
treated
at
100
ppm
of
carbaryl
and
above
with
a
dose
related
increase
in
incidence
and
severity.
There
was
no
evidence
of
local
irritation
or
hypertrophy
of
the
bladder
epithelium.
There
was
no
evidence
of
neoplastic
or
preneoplastic
changes
in
the
vascular
tissue
of
any
organs
examined.
The
study
is
classified
Acceptable
(non
guideline).
This
is
a
special
study
not
submitted
to
fulfill
a
data
requirement.
24
4.7
Mutagenicity
Adequacy
of
data
base
for
Mutagenicity:
The
data
base
for
mutagenicity
is
considered
complete
and
no
additional
studies
are
required
at
this
time.
A
recent
review
of
the
data
from
the
submitted
studies
and
the
published
literature
were
in
general
agreement
and
showed
that
carbaryl
was
clastogenic
in
vitro.
The
wide
variety
of
induced
aberrations
(both
simple
and
complex)
was
consistent
between
the
submitted
study
and
the
open
literature.
However,
there
were
inconsistencies
relative
to
the
requirement
for
S9
activation.
Nevertheless,
the
two
in
vivo
studies
for
micronuclei
induction
or
chromosome
aberrations
were
negative.
Similarly,
the
6
month
p53
knockout
transgenic
mouse
bioassay
(see
Section
4.6)
was
negative
up
to
a
high
level
(4000
ppm,
.
720
mg/
kg/
day)
that
approached
the
limit
dose
for
a
mouse
carcinogenicity
assay.
Carbaryl
was
also
negative
for
DNA
binding
in
the
livers
of
mice
treated
with
8000
ppm
for
2
weeks
but
the
study
was
considered
to
be
of
limited
sensitivity
by
the
CARC
Metabolism
Subgroup.
The
same
Subgroup
identified
epoxide
intermediates
of
carbaryl
which
were
found
to
be
conjugated
to
glucuronide,
"rapidly
metabolized
and
excreted
as
any
endogenous
epoxide
would
be".
Overall,
these
findings
indicate
that
carbaryl
produces
epoxides
and
its
DNA
reactivity
is
manifested
as
chromosomal
aberrations
in
cultured
mammalian
cells.
Other
in
vitro
studies
indicate
carbaryl's
effects
on
karyokinesis
and
cytokinesis,
as
well
as
stress
genes
associated
with
oxidative
damage.
Based
on
these
considerations,
it
was
concluded
that
there
is
a
concern
for
mutagenicity,
which
is
somewhat
lessened
because
of
the
lack
of
an
effect
in
in
vivo
mutagenicity
studies.
GENE
MUTATIONS
Mutagenicity
Salmonella
typhimurium/
Mammalian
Microsome
Mutagenicity
Assay
(Ames
test)
In
a
Salmonella/
mammalian
activation
gene
mutation
assay
(MRID
41370303),
carbaryl
technical
(99.3%)
was
initially
evaluated
in
the
Salmonella
typhimurium/
microsome
mutagenicity
assay
over
a
concentration
range
of
5
to
1000
µg/
plate.
The
test
material
was
not
mutagenic,
however
the
highest
assayed
dose
was
cytotoxic
in
S.
typhimurium
strains
TA98
and
TA100,
but
not
in
strains
TA1535,
TA1537,
or
TA1538.
Accordingly,
the
assay
was
repeated
with
six
concentrations
(10
to
2000
µg/
plate
+/
S9).
Results
from
the
repeat
assay
indicated
that
2000
µg/
plate
+/
S9
was
cytotoxic
in
strains
TA98
and
TA100,
and
the
remaining
doses
were
not
mutagenic.
It
is
concluded,
therefore,
that
carbaryl
technical
was
assayed
to
an
appropriately
high
concentration
with
no
evidence
of
mutagenicity
in
a
wellconducted
study.
The
study
is
classified
as
acceptable/
guideline
and
satisfies
the
guideline
requirements
(§
84
2)
of
bacterial
reverse
mutation
test.
Mutagenicity
Mammalian
Cells
in
Culture
Gene
Mutation
Assay
in
Chinese
Hamster
Ovary
(CHO)
Cells
In
a
mammalian
cells
in
culture
gene
mutation
assay
in
Chinese
Hamster
Ovary
(CHO)
Cells
(MRIDs
41370302,
41420201),
carbaryl
technical
(99.3%)
was
evaluated
in
two
nonactivated
and
three
25
S
9
activated
Chinese
hamster
ovary
(CHO)
cell
forward
mutation
assays.
The
findings
from
both
nonactivated
assays
were
in
good
agreement
and
indicated
that
over
a
concentration
range
of
1
to
300
µg/
mL,
the
test
material
did
not
induce
a
mutagenic
response.
Doses
$
200
µg/
mL
were
severely
cytotoxic
(<
10%
cell
survival),
and
<50%
of
the
cells
survived
exposure
to
$
50
µg/
mL.
Carbaryl
was
less
cytotoxic
in
the
presence
of
S9
activation
as
indicated
by
increased
survival
at
comparable
levels
in
the
preliminary
cytotoxicity
test
(e.
g.,
29.5%
survival
at
62.5
µg/
mL
S9
as
compared
with
95.7%
survival
at
62.5
µg/
mL
+S9)
and
the
initial
mutation
assay
(e.
g.,
18.1%
survival
at
100
µg/
mL
S9
as
compared
with
46.8%
at
100
µg/
mL
+S9).
There
was
no
definitive
evidence
of
increased
mutation
frequencies
(MFs)
in
this
trial.
The
second
S9
activated
trial
was
aborted
because
of
excessive
cytotoxicity
at
test
material
levels
of
$
10
µg/
mL.
Results
from
the
third
S9
activated
trial
(dose
range:
1
to
80
µg/
mL)
showed
severe
cytotoxic
effects
at
levels
$
60
µg/
mL;
no
evidence
of
mutagenic
effect
was
seen
at
the
remaining
doses.
The
results
of
the
assays
provide
no
clear
indication
of
a
mutagenic
response,
however,
the
study
does
not
fully
support
a
negative
conclusion.
The
conflicting
cytotoxicity
data
for
the
S9
activated
assays
provide
no
assurance
that
the
final
S9
activated
mutation
assay
was
conducted
over
an
appropriate
dose
range.
The
study
is
classified
as
unacceptable/
guideline
and
does
not
satisfy
the
guideline
requirements
(§
84
2)
for
an
in
vitro
mammalian
cell
gene
mutation
test.
CHROMOSOME
ABERRATIONS
Mutagenicity
Mammalian
Cells
in
Culture
Cytogenetic
Assay
Carbaryl
(technical)
was
assayed
for
clastogenic
effects
in
both
the
presence
and
absence
of
S9
activation
using
Chinese
hamster
ovary
(CHO)
cells
(MRID
41370304).
Because
of
severe
cell
cycle
delay,
which
was
more
pronounced
without
S9
activation,
a
20
hour
cell
harvest
was
selected
to
evaluate
seven
nonactivated
doses
ranging
from
5
to
100
:
g/
mL.
In
the
presence
of
S9
activation,
cells
exposed
to
carbaryl
at
doses
of
25,
50,
75,
100,
150,
200,
250,
and
300
:
g/
mL
were
harvested
30
hours
post
treatment.
Results
indicated
that
the
nonactivated
test
material
was
more
cytotoxic
than
the
S9
activated
test
material
(i.
e.,
few
metaphases
were
recovered
at
75
and
100
:
g/
mL
,
and
moderate
to
slight
cytotoxic
effects
were
seen
at
doses
$
10.0
:
g/
mL).
With
the
exception
of
a
single
rare
complex
aberration
(quadriradial)
scored
at
the
50.0
:
g/
mL
dose
level,
there
was
no
evidence
of
a
clastogenic
effect.
By
contrast,
in
the
S9
activated
assays,
all
scored
doses
(150,
200,
250,
and
300
:
g/
mL)
at
both
harvest
times
induced
significant
(p
0.01)
increases
in
the
percentage
of
cells
with
aberrations.
The
majority
of
S9
activated
doses
(both
harvests)
also
induced
significant
(p
0.01)
increases
in
the
percentage
of
cells
with
>1
aberration.
At
both
the
20
and
30
hour
harvest
times,
cytotoxicity
(i.
e.,
reduced
monolayers,
dead
cells,
and/
or
reduced
mitotic
cells)
were
observed
at
levels
$
200
:
g/
mL.
Induced
structural
damage
included
simple
(i.
e.,
chromatid
and
chromosome
breaks)
and
complex
aberrations
(i.
e.,
triadials,
quadriradials,
complex
rearrangements,
dicentrics
and
rings).
The
data
show
little
or
no
dose
responsiveness
and
the
lowest
reactive
level
of
carbaryl
was
not
determined.
It
was
concluded,
however,
that
the
study
was
technically
sound
and,
therefore,
acceptable/
guideline.
The
study
satisfies
the
Guideline
requirements
(§
84
2)
for
an
in
vitro
mammalian
cell
chromosomal
aberration
test.
Mutagenicity
Mouse
Micronucleus
Test
26
In
a
mouse
micronucleus
assay
(MRID
No:
44069301),
groups
of
five
male
and
five
female
CD
1
mice
received
single
oral
gavage
administrations
of
50,
100
or
200
mg/
kg
carbaryl
(99.9%)
once
daily
for
2
days.
Based
on
analytical
determinations,
average
daily
doses
were
.
34,
79
or
180
mg/
kg.
Mice
were
sacrificed
at
24
and
48
hours
postadministration
of
the
second
dose
and
harvested
bone
marrow
cells
were
examined
for
the
incidence
of
micronucleated
polychromatic
erythrocytes
(MPEs).
The
test
material
was
delivered
as
suspensions
prepared
in
0.5%
carboxymethyl
cellulose.
The
minimal
toxicity
(i.
e.,
lethargy
which
lasted
for
2
hours)
in
the
absence
of
cytotoxicity
to
the
target
cells
does
not
support
the
testing
of
the
maximum
tolerated
dose
(MTD).
The
positive
control
induced
the
expected
high
yield
of
MPEs
in
males
and
females.
Carbaryl
did
not
induce
a
clastogenic
or
aneugenic
effect
in
either
sex
at
any
dose
or
sacrifice
time.
However,
there
was
no
convincing
evidence
that
the
MTD
was
achieved.
The
study
is
classified
as
unacceptable/
guideline
and
does
not
satisfy
the
guideline
requirements(§
84
2;
OPPTS
870.5385)
for
in
vivo
cytogenetic
mutagenicity
data.
OTHER
MUTAGENIC
EFFECTS
Mutagenicity
UDS
Assay
In
a
UDS
Assay
in
primary
rat
hepatocytes
(MRID
41370301),
under
the
conditions
of
two
independent
trials,
six
doses
of
carbaryl
technical
(99.3%)
ranging
from
0.5
to
25.0
µg/
mL
in
the
first
assay
and
six
doses
ranging
from
5.0
to
25.0
µg/
mL
in
the
repeat
assay
did
not
induce
an
appreciable
increase
in
the
net
nuclear
grain
counts
of
treated
rat
hepatocytes.
Doses
>25.0
µg/
mL
were
severely
cytotoxic;
reduced
cell
survival
(
25%)
was
observed
at
25.0
µg/
mL
in
both
assays.
Although
an
increase
in
the
percentage
of
cells
with
$
6
grains
per
nucleus
was
seen
in
the
initial
test,
the
increase
was
confined
to
a
single
dose
(10
µg/
mL)
and
was
not
dose
related
or
reproducible.
The
study
demonstrated
that
carbaryl
is
not
genotoxic
in
this
test
system
at
doses
of
5.0
to
25.0
µg/
mL.
The
study
is
classified
as
acceptable/
guideline
and
satisfies
the
guideline
requirements
(§
84
2)
for
a
unscheduled
DNA
synthesis
in
mammalian
cells
in
culture.
27
STUDIES
FROM
THE
OPEN
LITERATURE
Studies
in
the
open
literature
indicate
that
Carbaryl
is
not
mutagenic
in
bacteria
but
produced
conflicting
results
in
Chinese
hamster
V79
gene
mutation
assays
[negative
in
the
study
of
Onfelt
and
Klasterska
(1984)
but
weakly
positive
minus
S9
metabolic
activation
as
reported
by
Ahmed
et
al.
(1977)].
Nonactivated
carbaryl
induced
aneuploidy
and
sister
chromatid
exchanges
in
V79
cells;
the
addition
of
S9
or
an
excess
of
glutathione
eliminated
these
responses
(Onfelt
and
Klasterska
1983,
1984).
In
the
former
study,
multiple
chromatid
exchanges
(quadriradials
and
complex
rearrangements)
plus
chromosome
breaks
were
also
induced
by
100
mM
carbaryl;
this
effect
was
largely
abolished
by
the
simultaneous
addition
of
S9
or
glutathione.
There
were
positive
data
for
DNA
damage
in
a
human
lymphoblastoid
cell
line
(induction
of
CYP1A1
genes);
carbaryl
also
activated
other
stress
genes
known
to
be
sensitive
to
oxidative
damage
(Delescluse
et
al.,
2001).
Also,
carbaryl
caused
depolymerization
of
spindle
microtubules
and
an
apparent
uncoupling
of
karyokinesis
and
cytokinesis
in
cultured
V79
cells
(Renglin
et
al,
1988,
1989).
In
contrast
to
the
in
vitro
data,
carbaryl
administered
by
oral
gavage
at
1/
3
of
the
LD50
(146
mk/
kg/
day)
for
2
consecutive
days
was
negative
for
micronuclei
induction
in
Swiss
albino
male
mice
(Usha
Rani
et
al.,
1980).
Carbaryl
was
also
negative
for
the
induction
of
chromosome
aberrations
in
bone
marrow
cells
of
Syrian
hamsters
treated
with
1/
10,
1/
5
and
½,
of
the
LD50
and
the
LD50
(Dzwonkowska
and
Hubner,
1986).
4.8
Neurotoxicity
Adequacy
of
data
base
for
Neurotoxicity:
Available
neurotoxicity
studies
are
adequate
to
satisfy
the
guideline
requirements.
There
was
no
evidence
of
delayed
neurotoxicity
in
hens.
In
the
acute
neurotoxicity
study
in
rats,
the
LOAEL
was
based
on
plasma,
RBC
and
brain
ChEI;
a
NOAEL
could
not
be
established.
In
the
subchronic
neurotoxicity
study
in
rats,
clinical
signs
of
toxicity
were
seen
at
the
same
dose
as
plasma,
whole
blood,
RBC
and
brain
ChEI.
There
was
no
evidence
of
structural
neuropathology
in
these
studies.
In
the
developmental
neurotoxicity
study
in
rats,
clinical
signs
of
toxicity
and
plasma
and
brain
ChEI
were
seen
in
maternal
animals
at
the
same
dose
as
changes
in
brain
morphometric
measurements
in
offspring.
The
HED
Hazard
Identification
Assessment
Committee
(HIARC)
determined
that
this
was
evidence
of
qualitative
susceptibility.
5
Carpenter,
C.
P.,
Weil,
C.
S.,
Palm,
P.
E.
et
al.
Mammalian
Toxicity
of
1
napthyl
N
methyl
carbamate
(Sevin
Insecticide).
J.
Agri.
Food
Chem.
9(
1):
30
39,
1961.
28
870.6100
Delayed
Neurotoxicity
Study
Hen
In
a
study
by
Carpenter
et
al
5
,
Carbaryl
was
negative
for
delayed
neuropathy
at
a
dose
of
2000
mg/
kg,
the
approximate
LD50
in
hens.
870.6200
Acute
Neurotoxicity
Screening
Battery
In
an
acute
neurotoxicity
study
(MRID
#
43845201
43845204),
groups
of
12
male
and
12
female
Sprague
Dawley
rats
were
administered
Carbaryl
technical
grade
in
0.5%
carboxymethylcellulose
/
0.1%
Tween
80
at
doses
of
10,
50,
or
125
mg/
kg/
day.
Doses
were
selected
on
the
basis
of
results
from
a
benchmark
toxicity
study
(MRID
#
43845201)
and
a
"time
of
peak
effects"
study
(MRID
#
43845202).
In
the
benchmark
study,
clinical
signs
of
toxicity
and
body
weight
loss
were
observed
at
50
mg/
kg/
and
above,
and
mortality
was
observed
at
500
mg/
kg
and
above.
In
the
time
of
peak
effects
study,
peak
effect
for
cholinesterase
inhibition
and
functional
observational
battery
changes
was
determined
to
be
0.5
to
1.0
hr
post
dose.
Body
weight
was
mildly
but
significantly
decreased
in
male
rats
at
the
125
mg/
kg
dose
level,
while
weight
gain
was
significantly
decreased
in
male
and
female
rats
for
days
0
7
of
the
study
at
125
mg/
kg.
Food
consumption
during
week
1
was
decreased
at
the
125
mg/
kg
dose
by
18
20%,
in
excess
of
the
decrease
in
body
weight
gain,
supporting
a
treatment
related
effect
at
the
high
dose
for
week
1
of
the
study.
Several
measurements
from
Functional
Observational
Battery
assessment
were
significantly
altered
at
the
50
and
125
mg/
kg
dose,
including
an
increased
incidence
of
tremors,
ataxic
gait,
decreased
body
temperature,
and
decreased
arousal.
Salivation
incidence
was
increased
at
the
high
dose,
as
was
hindlimb
splay.
Forelimb
and
hindlimb
grip
strength
were
decreased
significantly
at
the
high
dose.
Significant
decreases
in
total
motor
activity
were
observed
in
male
and
female
rats
at
all
dose
levels
tested.
Significant
inhibition
of
plasma,
blood,
and
brain
cholinesterase
(30
40%)
was
also
observed
in
both
sexes
at
the
10,
30
and
90
mg/
kg
doses.
Peak
inhibition
of
cholinesterase
occurred
during
the
time
of
FOB
and
motor
activity
measurements.
Based
on
the
data
in
this
study,
the
systemic
LEL
=
10
mg/
kg
for
male
and
female
rats,
based
on
significant
inhibition
of
red
cell,
plasma,
whole
blood,
and
brain
cholinesterase
at
the
10
mg/
kg
dose
level.
The
systemic
NOAEL
<
10
mg/
kg
for
male
and
female
rats.
Although
significant
signs
of
cholinergic
toxicity
were
observed
in
this
study,
there
was
no
definitive
evidence
of
a
neurotoxic
effect
for
Carbaryl
technical
grade
in
this
study.
This
study
is
classified
as
acceptable
and
satisfies
the
guideline
requirement
for
an
acute
neurotoxicity
study
(§
81
8)
in
rats.
870.6200
Subchronic
Neurotoxicity
Screening
Battery
In
a
subchronic
neurotoxicity
study
(MRID
44122601),
12
Crl:
CD(
SD)
BR
rats/
sex/
group
were
administered
technical
Carbaryl
(99.1%)
by
gavage
at
doses
of
0,
1,
10
or
30
mg/
kg/
day
for
13
weeks.
Cholinesterase
(RBC,
whole
blood,
plasma
and
brain)
determinations
were
done
on
an
additional
three
groups
of
five
rats/
sex/
group
at
Weeks
4,
8
and
13.
Neurobehavioral
screening,
consisting
of
Functional
Observational
Battery
(FOB)
and
motor
activity
evaluations,
was
performed
prior
to
treatment
and
during
29
Weeks
4,
8
and
13.
At
terminal
sacrifice,
six
animals/
sex/
dose
were
anesthetized
and
perfusion
fixed
in
situ
for
neuropathological
evaluation.
There
were
no
deaths
during
the
study.
There
was
an
increased
incidence
of
clinical
signs
of
toxicity,
including
slight
and
moderate
salivation
and
tremors,
in
the
30
mg/
kg/
day
males
and
females.
Body
weight
over
the
course
of
the
study
was
statistically
significantly
decreased
in
the
30
mg/
kg/
day
males
(14%)
and
females
(15%).
Body
weight
gain
for
these
groups
was
decreased
27%
in
males
and
37%
in
females,
compared
to
controls.
Food
consumption
was
decreased
during
most
of
the
study
for
the
30
mg/
kg/
day
males
and
females.
Males
and
females
in
the
30
mg/
kg/
day
group
had
a
statistically
significant
decrease
in
RBC
(M:
42
46%;
F:
52
55%),
whole
blood
(M:
49
51%;
F:
59
63%)
and
plasma
cholinesterase
values
(M:
63
69%;
F:
63
69%)
at
most
of
the
testing
periods.
Males
and
females
in
the
10
mg/
kg/
day
group
had
a
statistically
significant
decrease
in
RBC
(M:
26
38%;
F:
17
24%);
whole
blood
(M:
30
41%;
F:
21
26%)
and
plasma
cholinesterase
values
(M:
43
48%;
F:
23
30%).
There
was
a
statistically
significant
decrease
in
brain
cholinesterase
in
males
and
females
in
the
10
mg/
kg/
day
(M:
27
61%;
F:
20
58%)
and
30
mg/
kg/
day
(M:
36
80%;
F:
50
73%)
groups.
For
the
1
mg/
kg/
day
males,
there
were
statistically
significant
decreases
in
whole
blood
(13%)
at
week
13
and
for
plasma
(20%)
at
week
8.
These
changes
are
not
considered
toxicologically
significant
since
they
occurred
infrequently
and
were
relatively
minor
effects.
Multiple
qualitative
and
quantitative
FOB
parameters
were
affected
in
the
10
and
30
mg/
kg/
day
males
and
females,
including
the
following:
slight
tremors,
gait
alterations,
pinpoint
pupils,
increased
salivation,
reduced
extensor
thrust,
decreased
pinna
reflex,
reduced
number
of
rearings,
decreased
vocalizations,
decreased
body
temperature
and
decreased
forelimb
grip.
Reduced
number
of
defecations
was
observed
only
at
30
mg/
kg/
day.
There
was
an
occasional
alteration
at
the
1
mg/
kg/
day
dose.
At
week
8,
males
had
a
very
slight
increase
in
the
incidence
of
pinpoint
pupils
(incidence
in
control,
1,
10
and
30
mg/
kg/
day
groups
was
0/
12,
1/
12,
6/
12
and
10/
12,
respectively).
A
statistically
significant
decrease
in
forelimb
grip
was
observed
at
week
4
in
males
(values
for
control,
1,
10
and
30
mg/
kg/
day
groups
were
1060.8,
943.8,
943.8
and
950.0,
respectively).
The
number
of
defecations
was
statistically
reduced
in
females
at
week
13
(mean
number
of
defecations
in
control,
1,
10
and
30
mg/
kg/
day
groups
were
1.4,
0.2,
0.5
and
0.0,
respectively).
The
toxicological
significance
of
these
effects
in
the
1
mg/
kg/
day
group
is
questionable
since
the
incidence
was
either
low
or
there
was
no
dose
response
relationship.
Motor
activity
was
statistically
significantly
decreased
in
the
30
mg/
kg/
day
males
at
Week
4
and
the
30
mg/
kg/
day
females
at
Weeks
4
and
8.
On
necropsy,
there
was
an
increased
incidence
of
dark
areas
in
the
meninges
of
the
30
mg/
kg/
day
males;
these
animals
had
an
increased
incidence
of
hemorrhage
on
microscopic
examination.
One
female
in
the
30
mg/
kg/
day
group
also
had
retinal
atrophy.
There
were
no
differences
in
brain
length
or
width
measurements.
The
LOAEL
for
neurotoxicity
was
10.0
mg/
kg/
day
based
on
an
increased
incidence
of
FOB
changes;
the
NOAEL
was
1.0
mg/
kg/
day.
The
LOAEL
for
cholinesterase
inhibition
was
10.0
mg/
kg/
day
based
on
statistically
significant
decreases
in
RBC,
whole
blood,
plasma
and
brain
cholinesterase;
the
NOAEL
was
1.0
mg/
kg/
day.
30
The
subchronic
neurotoxicity
study
in
the
rat
is
classified
acceptable/
guideline
and
does
satisfy
the
guideline
requirement
for
a
subchronic
neurotoxicity
study
(OPPTS
870.6200)
in
the
rat.
870.6300
Developmental
Neurotoxicity
Study
In
a
developmental
neurotoxicity
study
(MRID
#
44393701,
44904204,
45456701,
45456702,
45456703),
26
pregnant
female
Sprague
Dawley
rats/
group
were
administered
carbaryl
(99.1%
a.
i.)
by
gavage
from
Gestation
Day
(GD)
6
through
Lactation
Day
(LD)
10
at
doses
of
either
0,
0.1,
1.0
or
10
mg/
kg/
day.
An
additional
6
pregnant
females/
group
were
dosed
at
the
same
levels
for
the
cholinesterase
(ChE)
phase
of
the
study.
ChE
measurements
were
done
pre
dosing
(GD
6)
and
post
dosing
at
time
of
peak
effect
(1
hour
post
dosing)
on
GD
6,
15
and
20
and
LD
4
and
10.
Functional
Observational
Battery
(FOB)
measurements
were
performed
at
approximately
0.5
and
2
hours
post
dosing
on
the
same
days
as
body
weight
measurements
during
the
dosing
period
(GD
0,
6,
9,
12,
15,
18
and
20
and
LD
4,
7,
11,
13
and
21).
Measures
of
reproductive
performance
were
evaluated.
Offspring
were
examined
for
body
weight,
physical
development
landmarks
(tooth
eruption
and
eye
opening),
FOB
assessments
(days
4,
7,
11,
13,
17
and
21)
and
motor
activity
(days
13,
17
and
21).
On
LD
11,
1
animal/
sex/
litter
was
sacrificed
for
brain
weights;
of
these,
six/
sex
were
randomly
selected
for
neuropathological
evaluation.
The
eyes
from
all
dose
groups
were
examined.
After
LD
21,
3
animals/
sex/
litter
were
separated
from
the
dams
and
constituted
the
F1
adult
generation.
These
animals
were
evaluated
for
body
weight,
physical
development
(vaginal
opening
and
preputial
separation),
motor
activity
(day
60),
startle
habituation
response
(days
22
and
60),
passive
avoidance
(day
23)
and
water
maze
behavior
(day
60).
After
completion
of
the
behavior
test
period
(at
approximately
10
weeks
of
age),
12
animals/
sex/
group
were
anesthetized
and
perfused
for
post
mortem
examination.
Tissues
from
6
animals/
sex
of
the
control
and
high
dose
group
were
processed
for
neuropathological
evaluation
and
morphometric
measurements;
the
eyes
from
the
low
and
mid
dose
group
of
all
perfused
animals
were
examined.
For
the
F0
generation
animals,
there
were
no
carbaryl
associated
deaths.
No
treatment
related
clinical
signs
of
toxicity
were
observed.
There
was
a
statistically
significant
decrease
(92%)
in
body
weight
gain
for
females
in
the
10
mg/
kg/
day
group
for
the
period
GD
6
9.
Unfortunately,
food
consumption
was
not
measured
during
the
study.
During
the
FOB
measurements,
the
incidence
of
females
in
the
10
mg/
kg/
day
group
with
decreased
pupil
size
(pinpoint
pupils)
was
increased
on
all
occasions
during
the
dosing
period.
An
increased
incidence
of
dams
with
slight
tremors
affecting
the
head,
body
and/
or
limbs
was
noted
on
the
majority
of
assessment
occasions
in
the
dosing
period.
There
were
also
occasional
occurrences
of
ataxic
gait/
overall
gait
in
capacity
which
was
considered
to
be
of
toxicological
significance
due
to
other
effects
upon
gait.
For
the
10
mg/
kg/
day
group,
RBC
and
whole
blood
ChE
levels
were
statistically
significantly
decreased
(28%
and
32
34%,
respectively)
on
GD
20
and
LD
10.
Although
the
plasma
ChE
levels
were
not
statistically
significantly
altered,
the
percentage
decreases
on
GD
20,
LD
4
and
LD
10
were
32
39%.
Brain
ChE
levels
were
statistically
significantly
decreased
(42%).
There
were
no
treatment
related
effects
on
gross
necropsy
findings
for
the
F0
generation
animals.
31
There
were
no
effects
observed
on
maternal
performance
parameters
of
pregnancy
rate,
gestation
index,
length
of
gestation,
numbers
of
live
pups,
dead
or
malformed
pups,
implantation
scars,
sex
ratio
or
postimplantation
loss.
There
was
a
slight
(P>
0.05)
increase
in
the
number
of
dead
pups
in
the
10
mg/
kg/
day
group,
however
the
value
was
within
the
historical
control
range
for
this
strain.
For
the
F1
generation
pups,
there
were
no
treatment
related
effects
on
pup
weight,
pup
survival
indices,
developmental
landmarks
(tooth
eruption
and
eye
opening),
FOB
measurements
or
motor
activity
assessments.
At
sacrifice
on
LD
11,
there
were
no
treatment
related
effects
on
brain
weight
and
gross
or
microscopic
pathology.
Significant
differences
noted
in
the
morphometric
measurements
included
an
increase
in
Line
B
of
the
right
forebrain
and
Line
F
of
the
left
cerebellum
in
the
10
mg/
kg/
day
males.
In
the
10
mg/
kg/
day
females,
Line
F
through
both
the
right
and
left
cerebellum
were
significantly
decreased
(15%
and
22%,
respectively).
For
the
F1
generation
adults,
there
were
no
treatment
related
effects
on
clinical
condition,
body
weight,
physical
development
(vaginal
opening
and
preputial
separation),
motor
activity,
auditory
startle
response,
passive
avoidance
and
water
maze
measurements.
At
sacrifice,
there
were
no
gross
or
microscopic
neuropathological
lesions
observed
for
animals
examined
in
this
study
that
were
attributable
to
treatment
with
the
test
article.
There
was
an
increased
incidence
of
retinal
fold/
rosette
in
the
10
mg/
kg/
day
group
(1/
12
for
control
vs.
4/
12
for
males;
0/
12
for
control
vs.
2/
12
for
females).
The
finding
was
not
considered
of
toxicological
significance
since
the
incidence
was
within
the
historical
control
range
for
males,
occurred
at
a
low
rate
and
was
not
dose
dependent.
For
the
morphometric
measurements,
there
was
a
significant
bilateral
decrease
in
Line
A
through
the
forebrain
(7.7
9.8%)
and
a
significant
increase
in
Line
F
through
the
right
cerebellum
of
the
10
mg/
kg/
day
males.
Increases
originally
noted
in
10
mg/
kg
adult
females
in
Line
G,
width
of
the
cerebellum,
were
found
to
be
based
on
erroneous
measurements,
and
additional
measures
were
submitted.
Now,
for
the
10
mg/
kg/
day
females,
there
were
significant
bilateral
increases
in
Line
F
through
the
cerebellum
(7.4
15%).
Measurements
of
the
size
of
the
thickness
of
lobes
and
of
the
granule
cell
layers
of
the
cerebellum
in
high
dose
pups
and
adults
did
not
differ
from
those
of
controls.
While
additional
statistical
analyses
by
the
registrant
indicated
no
treatment
related
effects,
HED's
additional
statisical
analyses
did
indicate
treatment
related
effects.
The
maternal
toxicity
LOAEL
was
10
mg/
kg/
day
based
on
decreased
body
weight
gain,
alterations
in
FOB
measurements
and
RBC,
plasma,
whole
blood
and
brain
cholinesterase
inhibition.
The
maternal
NOAEL
was
1.0
mg/
kg/
day.
The
developmental
neurotoxicity
LOAEL
was
10
mg/
kg/
day
based
on
a
bilateral
decrease
in
the
size
of
the
forebrain
(Line
A)
in
adult
males
(7.7
9.8%);
a
bilateral
decrease
in
the
length
of
the
cerebella
(Line
F)
in
female
pups
(15
22%);
and
a
bilateral
increase
in
the
length
of
the
cerebella
(Line
F)
in
female
adults
(7.4
15%).
The
developmental
NOAEL
was
1
mg/
kg/
day.
Morphometric
assessment
at
the
mid
and
low
doses
could
not
be
conducted
due
to
inadequate
tissue
storage;
however,
based
on
the
minimal
findings
at
the
LOAEL,
it
is
HED's
judgment
that
effects
would
be
unlikely
to
occur
at
1
mg/
kg/
day,
which
is
10%
of
the
LOAEL.
32
4.9
Metabolism
Adequacy
of
data
base
for
metabolism:
Available
metabolism
data
are
adequate
to
satisfy
the
guideline
requirements
and
have
delineated
the
metabolic
pathway
in
the
rat.
Carbaryl
was
broken
down
into
over
20
metabolites.
The
major
route
of
elimination
was
via
the
urine.
No
significant
tissue
accumulation
was
reported.
Additional
special
studies
have
been
conducted
to
determine
if
there
are
alterations
in
metabolism
at
high
doses.
870.7485
Metabolism
Rat
In
a
rat
metabolism
study
(MRID
#
43332101),
14
C
Carbaryl
was
administered
orally
in
carboxymethylcellulose
or
intravenously
in
sodium
phosphate
buffer
(pH
6.8)
to
groups
(5
sex/
dose)
of
male
and
female
Sprague
Dawley
rats
at
nominal
doses
of
1
mg/
kg
(single
and
repeated
low
oral
doses;
intravenous
dose)
and
50
mg/
kg
(single
high
oral
dose).
Absorption
was
essentially
complete
for
all
dose
groups
of
male
and
female
rats.
At
168
hours
post
dose,
there
were
negligible
percentages
of
the
dose
found
in
any
tissue
examined.
On
a
µg/
g
tissue
basis,
kidney
and
blood
were
found
to
contain
the
highest
concentrations
of
residual
radioactivity,
with
female
rats
showing
slightly
higher
values
than
males.
Excretion
of
carbaryl
derived
radioactivity
was
largely
through
urine,
where
88
95%
of
the
dose
was
recovered
for
all
dose
groups.
There
were
no
significant
dose
or
sex
related
differences
in
excretion.
Conjugated
metabolites
of
carbaryl
identified
in
this
study
included
the
glucuronic
acid
conjugate
of
dihydro
dihydroxy
carbaryl
(2.2%
of
the
dose),
the
S(
N
acetylcysteine)
conjugate
of
dihydro
hydroxy
carbaryl
(3.7%
of
the
dose),
naphthyl
glucuronide
(2.0%
of
the
dose),
and
naphthyl
sulfate
(6.4%
of
the
dose).
Non
conjugated
metabolites
identified
were
1
naphthol,
5
hydroxycarbaryl,
5,6
dihydro
5,6
dihydroxycarbaryl,
4
hydroxycarbaryl,
and
N(
hydroxymethyl)
hydroxycarbaryl.
These
accounted
for
14.5%,
12.8%,
8.2%,
6.3%,
and
5.7%
of
the
administered
dose,
respectively.
Three
new
metabolites
were
identified
in
this
study
which
were
the
N(
hydroxymethyl)
hydroxycarbaryl
metabolite,
hydroxy
desmethylcarbaryl
(0.5%
of
the
dose),
and
the
S(
N
acetylcysteinyl)
dihydro
dihydroxycarbaryl
conjugate.
Based
on
these
data,
a
metabolic
scheme
for
carbaryl
was
proposed.
This
study
is
classified
as
acceptable/
guideline
and
satisfies
the
data
requirements
for
a
metabolism
study
in
rats
under
Subdivision
F
guideline
§85
1.
Metabolism
Special
Study
In
a
rat
metabolism
study
(MRID
No.
44402501),
1
naphthyl
14
C
labeled
carbaryl
(ca
100%
a.
i.)
was
administered
to
15
month
old
male
Iffa
Credo
CD
(Sprague
Dawley
derived)
rats
(5
animals/
group)
as
a
single
oral
gavage
dose
of
50
mg/
kg
(group
A)
or
as
a
daily
oral
dose
of
2
mg/
kg
for
7
days
following
a
83
day
dietary
administration
with
non
radioactive
carbaryl
(25
animals/
group)
at
0
(group
B),
250
(group
C),
1500
(group
E),
or
7500
ppm
(group
D).
This
study
was
designed
to
"investigate
the
mechanisms
that
caused
the
appearance
of
an
increased
incidence
of
tumors
during
the
final
year
of
a
chronic
dietary
feeding
study
in
the
rat
at
the
high
dose
level
of
7500
ppm."
In
all
dietary
dosing
regimens,
urinary
and
fecal
excretion
totaled
96
103%
of
the
administered
dose.
Most
of
the
radioactivity
was
eliminated
in
the
urine
and
feces
within
24
hours
after
dosing.
In
the
33
group
A,
86%
and
11%
of
the
test
compound
administered
was
excreted
in
the
urine
and
feces,
respectively,
over
a
7
day
period
after
a
single
dose
via
gavage
of
radiolabeled
carbaryl
at
50
mg/
kg.
In
the
groups
B
E
(0,
250,
1500,
and
7500
ppm),
3
days
after
the
7th
consecutive
administration
of
radiolabeled
carbaryl,
79
89%
and
7
10%
of
the
total
administered
dose
(sum
of
the
7
daily
doses)
were
excreted
in
the
urine
and
feces,
respectively.
Tissue
distribution
study
showed
that
the
levels
of
radioactivity
in
the
tissues
of
the
animals
from
group
A
were
0.4%
of
the
administered
dose
at
sacrifice
(168
hours
after
dosing).
In
groups
B
E,
the
levels
of
radioactivity
in
the
tissues
ranged
from
0.4
0.8%
of
the
administered
dose
3
days
after
the
7th
dose
of
radiolabeled
carbaryl
at
2
mg/
kg.
This
indicates
that
the
potential
for
bioaccumulation
of
carbaryl
in
rats
is
minimal.
HPLC
analysis
of
carbaryl
metabolites
in
24
hour
urine
samples
showed
a
total
of
23
components.
Four
components
identified
by
LC/
MS
technique
were
as
follows:
UMET/
8
(trans
5,6
dihydro
5,6
dihydroxy
1
naphthyl
N
methylcarbamate)
(accounted
for
3.75
6.38%
of
the
dose);
UMET/
11
(glucuronide
of
dihydro
dihydroxy
1
naphthyl
N
methylcarbamate)
(18.55%
28.46%
of
the
dose);
UMET/
18
(
naphthyl
$
D
glucuronide
sodium
salt
or
"
naphthyl
sulfate
potassium
salt
(15.69
21.75
%
of
the
dose);
and
UMET/
23
(naphthyl
sulfate)
(17.78%
30.01%
of
the
dose).
A
total
of
20
components
was
detected
in
the
24
hour
feces
by
HPLC
analysis.
One
component
(FMET/
15)
was
identified
as
parent
and
accounted
for
0.2
1.4%
of
the
administered
dose
by
LC/
MS
technique.
The
remaining
19
components
were
not
identified
because
the
levels
of
radioactivity
in
these
components
were
too
low.
There
were
2
major
metabolites
in
the
tissues
from
groups
B
E
at
6
hours
after
administration
of
14
Ccarbaryl
These
metabolites
were
confirmed
by
LC/
MS
analysis
as
naphthyl
sulfate
(found
in
plasma,
kidney,
and
urinary
bladder)
and
naphthyl
glucuronide
(found
in
the
kidney
and
urinary
bladder).
Quantitative
identification
for
these
metabolites
was
not
available
because
the
levels
of
radioactivity
in
these
tissues
were
too
low.
The
sulfate
conjugation
pathway
appears
to
be
saturable
following
a
subchronic
(83
day)
feeding
of
carbaryl
at
a
high
dose
(group
D,
7500
ppm).
This
saturation
of
the
sulfate
conjugation
pathway
is
seen
in
the
urinary
levels
of
UMET/
23
(naphthyl
sulfate)
between
the
dose
groups
following
the
83
day
dietary
administration
of
non
radioactive
carbaryl.
The
level
of
radioactivity
associated
with
UMET/
23
(naphthyl
sulfate)
was
higher
(23
27%
of
the
dose)
in
0,
250,
and
1500
ppm
dose
groups
and
lower
(12%
of
the
dose)
in
the
7500
ppm
group.
On
the
other
hand,
the
level
of
radioactivity
associated
with
UMET/
11
(naphthyl
glucuronide)
was
lower
(15
21%
of
the
administered
dose)
in
0,
250,
and
1500
ppm
dose
groups
and
higher
(28%)
in
the
group
7500
ppm
group.
Statistically
significant
decreases
(p<
0.05
or
p<
0.01)
in
body
weight
(9
20%)
when
compared
to
the
control
group
were
observed
only
in
the
7500
ppm
group
as
early
as
study
day
14
and
sustained
throughout
the
remainder
of
the
study.
In
the
7500
ppm
group,
the
statistically
significant
decreases
(p<
0.05
or
p<
0.01)
in
food
consumption
were
observed
at
week
1
(74%),
week
2
(61%),
week
3
(40%),
and
weeks
4
11
(19
31%).
In
the
1500
ppm
group,
the
statistically
significant
decreases
(p<
0.05)
in
food
consumption
were
observed
at
week
5
(8%),
week
10
(21%),
and
week
11
(12%).
34
Significant
increases
(statistical
analyses
were
not
performed)
in
kidney,
spleen,
and
thyroid
weights
were
observed
in
the
1500
or
7500
ppm
groups
when
compared
to
the
control
group.
Absolute
and
relative
liver
weights
increased
18%
and
39%,
respectively,
at
7500
ppm.
Absolute
spleen
weight
increased
30%
at
7500
ppm
and
relative
spleen
weight
increased
24%
and
30%
at
7500
and
1500
ppm,
respectively.
Absolute
thyroid
weight
increased
63%
and
69%
at
7500
and
1500
ppm,
respectively,
and
relative
thyroid
weight
increased
103%
and
121%
at
7500
and
1500
ppm,
respectively.
Statistically
significant
increases
(p<
0.01)
in
total
glutathione
concentrations
(higher
by
79%
per
g
of
liver
or
102%
per
g
of
protein)
were
observed
at
7500
ppm
only,
compared
to
the
controls.
The
incidences
of
hepatocellular
adenoma
(benign)
were
1/
5,
0/
5,
0/
5,
and
2/
5
at
0,
250,
1500,
and
7500
ppm,
respectively.
Although
the
authors
concluded
that
"there
was
no
treatment
related
change
in
the
incidence
of
tumors
under
carbaryl
treatment,"
definite
conclusion
cannot
be
made
from
this
finding
based
on
the
limited
number
of
animals
used.
Significant
treatment
related
changes
were
noted
in
liver,
thyroid
glands,
and
kidneys
at
7500
ppm
only.
The
incidences
of
centrilobular
hypertrophy
of
the
hepatocytes,
pericholangitis
(an
inflammatory
cell
infiltrate
around
biliary
ducts),
and
bile
duct
hyperplasia
were
5/
5,
3/
5,
and
3/
5,
respectively.
The
incidences
of
follicular
cell
hypertrophy
of
the
thyroid
glands
were
0/
5,
3/
5,
5/
5,
and
5/
5
and
the
incidences
of
transitional
cell
hyperplasia
of
the
renal
pelvis
were
0/
5,
0/
5,
1/
5
and
2/
5
at
0,
250,
1500,
and
7500
ppm,
respectively.
This
metabolism
study
in
the
rat
is
classified
acceptable
for
its
intended
purpose
of
investigating
"the
mechanisms
that
caused
the
appearance
of
an
increased
incidence
of
tumors
during
the
final
year
of
a
chronic
dietary
feeding
study
in
the
rat
at
the
high
dose
level
of
7500
ppm."
Although
the
study
supplies
some
information
to
the
Agency,
this
study
does
not
satisfy
the
guideline
requirement
for
a
metabolism
study
(85
1)
in
rats.
Metabolism
Special
Study
The
present
investigation
(MRID
#
43832601)
was
conducted
to
identify
and
phenotype
the
potential
for
Carbaryl
to
induce
hepatic
cytochrome
P
450
in
male
CD
1
mice
following
dietary
administration
of
8000
ppm
Carbaryl
in
the
diet.
The
data
in
this
study
represent
results
from
mice
used
in
a
previous
study
(MRID
#
432822
01)
whose
livers
had
been
stored
for
biochemical
analyses.
These
mice
had
received
pre
treatment
with
8000
ppm
(1143
mg/
kg/
day)
Carbaryl
for
14
days.
The
results
of
biochemical
analyses
in
the
liver
can
be
summarized
as
follows:
Carbaryl
pre
treatment
produced
significant
increases
in
microsomal
protein
(132%
of
control),
cytochrome
P
450
(134%
of
control),
ethoxyresorufin
O
deethylase
activity
(190%
of
control),
pentoxyresorufin
O
depentylase
activity
(313%
of
control),
and
increases
in
specific
testosterone
hydroxylase
activities
(6
alpha,
2ß,
11ß,
and
16ß
hydroxylase
activities).
Taken
together,
these
data
appear
to
indicate
a
`phenobarbital
type'
of
induction
of
liver
xenobiotic
metabolizing
enzymes
as
a
result
of
Carbaryl
pre
treatment
at
a
high
oral
dose
(1154
mg/
kg/
day).
The
similarity
of
the
pattern
of
induction
of
liver
xenobiotic
metabolizing
enzymes
by
Carbaryl
and
phenobarbital
is
supported
in
part
by
literature
data
(Kelley
et
al.,
Biochem.
Pharmacol.
15;(
39)
12:
1991
1998).
While
this
study
provides
useful
information
on
the
general
type
of
induction
observed
after
pretreatment
with
a
high
oral
dose
of
Carbaryl,
the
actual
relationship
of
induction
to
35
Carbaryl
toxicity
was
not
addressed,
as
no
metabolites
of
Carbaryl
after
this
type
of
exposure
were
investigated.
This
study
is
classified
as
acceptable
(non
guideline)
and
demonstrates
the
inductive
effect
of
repeated
high
dose
exposure
to
Carbaryl
by
the
oral
route.
Metabolism
Special
Study
In
a
special
study
(MRID
#
43282201),
[1
14
C]
naphthyl
N
methylcarbamate
(14
C
carbaryl)
was
tested
for
the
ability
to
bind
to
liver
DNA
in
male
CD1
mice
treated
with
a
single
radiolabelled
dose
of
carbaryl
(75
mg/
kg)
or
in
mice
pretreated
with
8000
ppm
(approximately
1143
mg/
kg/
day)
unlabelled
carbaryl
in
the
diet
for
two
weeks
followed
by
a
single
75
mg/
kg
radiolabelled
dose.
Binding
of
radiolabel
to
chromatin
protein
isolated
from
the
livers
of
mice
treated
with
a
single
dose
or
in
pretreated
mice
was
similar
(specific
activities
ranging
from
340.3
537.0
dpm/
mg).
No
radioactivity
was
detectable
in
DNA
samples
isolated
from
mice
treated
with
radiolabelled
carbaryl
(Covalent
Binding
Index
<
0.1).
According
to
the
report,
this
maximum
binding
ability
of
carbaryl
is
more
than
5
orders
of
magnitude
below
the
Covalent
Binding
Index
of
aflatoxin
B1,
and
more
than
4000
times
lower
than
the
Covalent
Binding
Index
for
2
acetylaminofluorene.
This
study
demonstrated
the
interaction
of
carbaryl
with
chromatin
protein,
but
no
significant
interaction
with
DNA
in
the
liver
of
male
CD1
mice
treated
with
either
a
single
75
mg/
kg
dose
or
in
mice
pretreated
with
8000
ppm
(1143
mg/
kg/
day)
carbaryl
in
the
diet
followed
by
a
single
75
mg/
kg
radiolabelled
dose.
This
study
was
not
conducted
to
satisfy
a
specific
guideline
requirement,
but
fulfills
the
purpose
for
which
it
was
conducted.
870.7600
Dermal
Absorption
Rat
Two
dermal
absorption
studies
in
rats
were
conducted.
In
the
study
with
a
formulation
containing
43.9%
carbaryl
(MRID
43552901),
animals
were
exposed
for
0.5,
1,
2,
4,
10
or
24
hours
at
doses
of
35.6,
403
or
3450
µg/
cm
2
.
Percent
absorbed
ranged
from
2.14
to
24.9,
1.01
to
24.7
and
0.07
to
3.17
for
the
35.6,
403
or
3450
µg/
cm
2
doses,
respectively
(see
Section
5.2
below).
The
HIARC
determined
that
a
12.7%
absorption
(relative
to
an
oral
dose)
should
be
used
for
risk
assessment.
This
rate
was
based
on
the
highest
absorption
rate
at
10
hours,
which
is
considered
the
duration
of
possible
occupational
exposure
during
a
work
day.
36
5.0
TOXICITY
ENDPOINT
SELECTION
5.1
See
Section
9.2
for
Endpoint
Selection
Table
(page
51).
5.2
Dermal
Absorption
Dermal
Absorption
Factor:
12.7
%
from
MRID
43552901
(findings
discussed
above)
The
dermal
absorption
factor
is
required
for
long
term
dermal
and
inhalation
risk
assessments
since
oral
doses
were
selected
for
these
exposure
periods.
In
a
dermal
absorption
study
(MRID
#
43552901),
radiolabeled
14
C
Carbaryl
LXR
Plus
(43.9%
a.
i.)
was
applied
to
the
skin
of
three
groups
of
four
male
rats/
group
at
doses
of
35.6,
403
or
3450
µg/
cm
2
for
0.5,
1,
2,
4,
10
or
24
hours.
The
ranges
for
percent
of
carbaryl
absorbed
for
the
35.6,
403
and
3450
µg/
cm
2
groups
were
2.14
24.9,
1.01
24.7
and
0.07
3.17,
respectively;
the
percent
absorbed
at
10
hours
was
12.7,
7.44
and
1.93,
respectively.
This
study
is
classified
as
Acceptable
(guideline)
and
satisfies
the
guidelines
for
a
dermal
absorption
study.
In
a
dermal
absorption
study
(MRID
#
43339701),
radiolabeled
14
C
Carbaryl
Sevin
(80.1%
a.
i.)
was
applied
to
the
skin
of
three
groups
of
four
male
rats/
group
at
doses
of
63,
626
or
3410
µg/
cm
2
for
0.5,
1,
2,
4,
10
or
24
hours.
The
ranges
for
percent
of
carbaryl
absorbed
for
the
63,
626
and
3410
µg/
cm
2
doses
were
0.66
16.6,
<0.01
1.27
and
0.07
1.2,
respectively;
the
percent
absorbed
at
10
hours
was
8.90,
0.62
and
0.48,
respectively.
This
study
is
classified
as
Acceptable
(guideline)
and
satisfies
the
guidelines
for
a
dermal
absorption
study.
5.3
Classification
of
Carcinogenic
Potential
5.3.1
The
CARC
concluded
that
carbaryl
was
carcinogenic
to
male
mice
at
doses
which
were
adequate
and
not
excessive.
Tumors
in
male
and
female
rats
and
female
mice,
as
well
as
other
tumors
in
male
mice,
occurred
at
excessively
toxic
high
dose
levels.
However,
preneoplastic
lesions
in
the
target
organs
in
male
rats
occurred
at
the
mid
dose
level
which
was
below
the
dose
adequate
for
testing
the
carcinogenic
potential
of
carbaryl.
The
findings
of
the
rat
combined
chronic
toxicity/
carcinogenicity
study
are
discussed
below.
1.
The
reanalyses
of
rat
tumor
data
showed
that
male
rats
had
significant
increasing
trends
and
significant
differences
in
pair
wise
comparisons
of
the
7500
ppm
dose
group
with
the
controls
for
thyroid
follicular
cell
adenomas
and
combined
adenomas/
carcinomas,
as
well
as
for
urinary
bladder
transitional
cell
papillomas,
carcinomas,
and
combined
papillomas/
carcinomas,
all
at
p<
0.01.
The
increase
in
the
incidence
of
combined
thyroid
follicular
cell
adenomas/
carcinomas
at
37
7500
ppm
was
driven
by
the
adenomas.
At
7500
ppm,
the
incidences
of
thyroid
follicular
cell
adenomas,
as
well
as
combined
urinary
transitional
cell
papillomas
and
carcinomas,
exceeded
their
respective
range
for
the
historical
controls.
The
female
rats
had
a
significant
increasing
trend
(p<
0.01)
and
a
significant
increase
by
pair
wise
comparison
of
the
7500
ppm
dose
group
with
the
controls
for
hepatocellular
adenomas
(p<
0.05).
The
re
read
of
tumor
data
by
the
Pathology
Working
Group
(PWG)
showed
that
the
female
rats
had
a
significant
increasing
trend
for
urinary
bladder
transitional
cell
papillomas,
carcinomas
and
combined
papillomas/
carcinomas,
all
at
p<
0.01.
There
were
significant
differences
in
the
pair
wise
comparisons
of
the
7500
ppm
dose
group
with
the
controls
for
urinary
bladder
transitional
cell
papillomas
(p<
0.05),
carcinomas
(p<
0.05),
and
combined
carcinomas/
papillomas
(p<
0.01).
The
incidences
of
hepatocellular
adenomas,
urinary
bladder
transitional
cell
papillomas
and
urinary
transitional
cell
carcinomas
exceeded
the
respective
ranges
for
the
historical
controls.
The
CARC
noted
that
at
the
week
53
necropsy,
transitional
epithelial
hyperplasia,
a
preneoplastic
stage,
was
observed
in
the
urinary
bladder
of
mid
dose
tested
(MDT)
males
and
highest
dose
tested
(HDT)
males
and
females.
After
the
4
week
recovery
period,
this
change
was
still
present
in
HDT
males
and
females.
At
the
terminal
necropsy,
the
transitional
cell
hyperplasia
was
observed
in
HDT
males
and
females,
along
with
an
increased
incidence
of
squamous
cell
metaplasia,
high
mitotic
index
and
atypia.
The
HDT
was
judged
to
be
excessive
based
on
a
significant
(p<
0.5)
decrease
in
body
weight
gains
during
week
13
for
males
and
females
by
40%
and
52%,
respectively,
as
compared
to
controls.
Decreased
food
efficiency
and
alterations
in
hematology
and
clinical
chemistry
values
were
also
reported
in
both
sexes
at
the
high
dose
level.
By
weeks
52
53,
plasma,
RBC
and
brain
cholinesterase
(ChE)
activities
were
significantly
(p<
0.05)
decreased
in
males
by
40%,
22%
and
28%,
respectively,
and
in
females
by
56%,
36%
and
37%,
respectively,
as
compared
to
controls.
By
week
104,
plasma,
RBC
and
brain
ChE
activities
were
significantly
decreased
in
males
by
42%,
30%
and
9%,
respectively,
and
in
females
by
46%,
38%
and
22%,
respectively.
The
MDT
was
judged
to
be
below
the
adequate
dose
for
testing
the
carcinogenic
potential
of
carbaryl.
At
this
dose,
there
was
no
effect
on
body
weight/
body
weight
gain
and
only
minor
ChE
inhibition
(less
than
20%
inhibition
of
plasma,
RBC
and
brain
ChE
in
males
and
females
at
week
53,
except
for
26%
inhibition
of
RBC
in
females;
at
week
105,
only
female
RBC
and
brain
ChE
were
decreased
(22%
and
16%,
respectively).
The
CARC
noted
that
the
MDT
male
rats
had
transitional
cell
hyperplasia
of
the
bladder,
a
preneoplastic
lesion,
at
the
week
53
necropsy.
If
the
dose
had
been
adequate,
bladder
tumors
seen
at
the
HDT
may
have
occurred
at
the
MDT.
2.
The
reanalyses
of
mouse
tumor
data
showed
that
male
mice
had
significant
increasing
trends
in
kidney
tubule
cell
adenomas
(p<
0.05),
carcinomas
(p<
0.05)
and
combined
adenomas/
carcinomas
(p<
0.01).
In
mice,
hemangiomas
in
the
liver
and
spleen
can
progress
to
hemangiosarcomas.
Therefore,
the
incidence
of
hemangiomas
and
hemangiosarcomas
at
various
sites
was
combined
and
analyzed.
There
were
significant
differences
(p<
0.05)
in
the
pair
wise
comparison
of
the
$
100
ppm
(all
doses
tested)
with
the
controls
for
hemangiosarcomas
and
in
combined
hemangiomas/
hemangiosarcomas
at
1000
and
8000
ppm.
In
addition,
a
significant
difference
in
the
pair
wise
comparison
of
the
8000
ppm
dose
group
with
controls
was
noted
for
combined
kidney
tubule
cell
adenomas/
carcinomas
(p<
0.05).
38
The
female
mice
had
significant
increasing
trend
in
hepatocellular
adenomas
(p<
0.01),
combined
hepatocellular
adenomas/
carcinomas
(p<
0.01),
hemangiosarcomas
(p<
0.01),
and
combined
hemangiomas/
hemangiosarcomas
(p<
0.05).
There
were
also
significant
differences
in
the
pairwise
comparison
of
the
8000
ppm
dose
group
with
the
controls
for
hepatocellular
adenomas
(p<
0.05),
combined
hepatocellular
adenomas/
carcinomas/
hepatoblastomas
(p<
0.01),
and
hemangiosarcomas
(p<
0.05).
Appropriate
historical
control
data
for
various
types
of
tumors
were
not
available
for
comparison.
However,
based
on
recently
submitted
historical
control
data
on
vascular
tumors
in
the
liver
and
spleen
(sites
for
most
hemangiomas/
hemangiosarcomas),
the
incidence
of
hemangiosarcomas
exceeded
the
range
for
the
historical
controls
in
both
male
and
female
mice.
The
CARC
considered
the
dosing
at
the
HDT
in
male
and
female
mice
to
be
excessive
because
the
decrease
in
body
weight
gain,
clinical
signs
and
ChE
inhibition,
and
histopathological
changes
in
various
organs
were
indicative
of
excessive
toxicity.
The
CARC
concluded
that
the
malignant
vascular
tumors
(hemangiosarcomas)
in
male
mice
occurred
at
doses
which
were
adequate
and
not
excessive.
In
females
these
tumors
occurred
only
at
the
highest
dose
which
was
excessively
toxic.
Nevertheless,
the
findings
in
female
mice
were
supportive
of
vascular
tumors
in
male
mice.
Carbaryl
produces
epoxides
and
its
genotoxicity
is
manifested
as
chromosomal
aberrations
in
cultured
mammalian
cells
while
older
in
vivo
studies
indicate
negative
results
for
aberrations.
More
recent
studies
with
cultured
cells
have
demonstrated
effects
on
microtubule
assembly,
karyokinesis
and
cytokinesis
as
well
as
stress
genes
associated
with
oxidative
damage.
5.3.2
Classification
of
Carcinogenic
Potential
In
accordance
with
the
EPA
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(July,
1999),
the
CARC
classified
carbaryl
into
the
category
"Likely
to
be
carcinogenic
to
humans"
based
on
the
following
weight
of
the
evidence
considerations:
1.
Carbaryl
induced
a
statistically
significant
increase
in
urinary
bladder
tumors
in
male
and
female
rats,
thyroid
tumors
in
male
rats
and
liver
tumors
in
female
rats.
These
tumors
were
induced
at
an
excessively
toxic
dose
(7500
ppm)
and,
therefore,
were
not
relevant
for
human
cancer
risk
assessment.
However,
there
was
evidence
of
preneoplastic
lesions
in
the
bladder
in
males
at
1500
ppm,
a
dose
which
was
below
the
adequate
dose
for
testing
the
carcinogenic
potential
of
carbaryl.
In
mice,
a
treatment
related
increase
in
malignant
vascular
tumors
(hemangiosarcomas)
was
noted
in
males
at
all
doses,
both
excessive
and
adequate,
whereas
in
females,
this
same
tumor
type
was
seen
only
at
excessive
doses.
2.
Carbaryl
is
clastogenic
in
in
vitro
studies
with
effects
on
aberrations;
aneuploidy
associated
events
are
also
observed
and
further,
a
single
report
from
the
published
literature
suggests
that
carbaryl
may
induce
oxidative
stress.
These
types
of
effects
may
contribute
to
carbaryl
induced
tumors.
Nevertheless,
carbaryl
is
negative
for
micronucleus
induction
in
one
mouse
strain,
not
clastogenic
in
Syrian
hamsters,
and
negative
in
a
p53
knockout
transgenic
mouse
bioassay.
39
5.3.3
Quantification
of
Carcinogenic
Potential
The
Committee
recommended
a
low
dose
linear
extrapolation
approach
using
all
dose
levels
for
the
quantification
of
human
cancer
risk
based
on
the
most
potent
vascular
tumors
in
mice.
This
approach
was
supported
by
the
lack
of
confirmation
of
a
mode
of
action.
The
Q1*,
based
on
the
CD
1
mouse
dietary
study
with
¾
Interspecies
Scaling
Factor,
is
8.75
x
10
4
(mg/
kg/
day)
1
in
human
equivalents.
6.0
FQPA
CONSIDERATIONS
6.1
Degree
of
Concern
Analysis
and
Residual
Uncertainties
The
HIARC
concluded
that
there
is
no
residual
concern
in
the
two
generation
reproduction
study
because
the
dose
response
effects
in
pups
are
well
characterized
and
the
NOAEL
for
the
offspring
effects
is
above
that
was
used
for
establishing
the
chronic
Reference
Dose
(RfD)
for
chronic
dietary
risk
assessment.
The
HIARC
selected
the
LOAEL
of
3.1
mg/
kg/
day
established
in
the
chronic
toxicity
study
in
dogs
for
establishing
the
chronic
RfD.
Since
a
LOAEL
was
used,
an
additional
uncertainty
factor
of
3X
was
applied
(i.
e,
lack
of
a
NOAEL)
to
the
LOAEL.
Although
a
NOAEL
was
not
established
in
this
study,
the
HIARC
determined
that
a
3X
was
adequate
(as
opposed
to
a
higher
value)
because:
1)
cholinesterase
inhibition
in
females
was
not
accompanied
by
clinical
signs;
2)
no
inhibition
was
seen
for
any
cholinesterase
compartment
in
males
at
this
dose;
3)
the
magnitude
of
inhibition
of
plasma
cholinesterase
inhibition
(12
23%
decrease)
was
comparable
to
the
magnitude
of
inhibition
(22%)
seen
in
the
5
week
study
in
dogs
indicating
no
cumulative
effects
following
long
term
exposure;
4)
the
study
was
wellconducted
and
there
are
sufficient
data
from
subchronic
and
chronic
duration
studies
in
the
other
species
which
support
cholinesterase
inhibition
as
the
critical
effect.
In
addition,
based
on
the
cholinesterase
inhibition
data,
the
dog
appears
to
be
more
sensitive
than
the
rat
in
long
term
studies.
Furthermore,
use
of
the
LOAEL
of
3
mg/
kg/
day
from
the
1
year
dog
study
with
an
uncertainty
factor
of
300
results
in
a
NOAEL
of
1
mg/
kg/
day.
This
extrapolated
NOAEL
is
identical
to
that
of
the
offspring
NOAEL
of
1.0
mg/
kg/
day
established
in
the
the
developmental
neurotoxicity
study.
Thus,
the
NOAEL
of
1
mg/
kg/
day
used
for
establishing
the
chronic
RfD
is
below
the
NOAEL
of
5
mg/
kg/
day
for
offspring
toxicity
and
the
chronic
RfD
would
be
protective
of
the
effects
of
concern
for
infants
and
children
following
chronic
dietary
exposures.
With
regard
to
the
developmental
neurotoxicity
study,
the
HIARC
concluded
that
there
was
a
low
level
of
concern
based
on
the
following
residual
uncertainties
°
The
first
uncertainty
was
the
lack
of
a
demonstrated
effect
level
since
morphometric
measurements
of
brains
in
the
offsprings
were
not
performed
at
the
mid
dose
(1
mg/
kg/
day).
However,
this
concern
was
negated
since
even
at
the
high
dose
of
10
mg/
kg/
day,
the
morphometric
changes
were
minimal
and
therefore,
it
is
unlikely
that
adverse
effects
would
be
seen
at
1
mg/
kg/
day,
which
is
10%
of
the
LOAEL.
40
°
The
second
uncertainty
was
the
lack
of
comparative
data
in
adults
and
offspring
for
cholinesterase
inhibition.
This
concern
was
negated
since
no
FOB
alterations
were
seen
in
pups.
Other
studies
in
the
data
base
have
shown
that
when
FOB
alterations
were
seen
in
adult
animals,
they
are
usually
accompanied
with
cholinesterase
inhibition.
Also,
the
results
of
the
National
Institute
for
Environmental
Health
Sciences
study
(discussed
below)
showed
no
difference
in
cholinesterase
inhibition
in
pups
and
adults.
There
was
a
doserelated
decrease
in
cholinesterase
activity
in
the
brain
and
blood
of
dams
at
gestation
day
19
and
fetuses
taken
at
this
time
also
showed
a
very
similar
level
in
fetal
brain
cholinesterase.
The
HIARC
concluded,
that
the
NOAEL
of
1
mg/
kg/
day
selected
for
establishing
the
acute
RfD
would
address
the
low
level
of
concern
for
the
residual
concerns
and
would
be
protective
of
the
effects
of
concern
for
infants
and
children
following
a
single
oral
exposure.
6.2
Hazard
Based
Special
FQPA
Safety
Factor
Recommendation
The
HIARC
concluded
that
the
hazard
based
special
FQPA
safety
factor
should
be
reduced
to
1x
based
on
the
following
reasons:
1.
The
toxicology
database
is
complete
2.
There
was
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
in
rat
or
rabbit
fetuses
following
in
utero
exposures
3.
There
was
evidence
of
qualitative
susceptibility
and
a
low
level
of
concern
due
to
some
residual
uncertainties
in
the
developmental
neurotoxicity
study.
However,
as
discussed
in
Section
I.
3,
the
acute
RfD
would
address
these
residual
uncertainties
and
would
be
protective
of
the
pre
pre/
post
natal
toxicity
following
an
acute
dietary
exposure.
4.
There
was
evidence
of
increased
susceptibility
in
the
offsprings
in
the
two
generation
reproduction
study,
but
there
was
no
residual
uncertainties.
The
chronic
RfD
would
be
protective
of
the
pre
pre/
post
natal
toxicity
following
chronic
dietary
exposures.
5.
The
dose
selected
for
residential
exposures,
would
be
protective
of
the
pre
pre/
post
natal
toxicity
following
non
dietary
exposures.
41
7.0
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1®
42
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139,
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52,
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C
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92
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Wisconsin,
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HWI
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MRID
43832601.
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H.
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Liver
Cytochrome
P
450
Inducer
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1
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Geigy
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94/
23,
October
21,
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MRIDs
43845201
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W.
et
al
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Study
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MRID
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Brooks,
W.
et
al
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Study
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Course
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W.
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the
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Effects
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Single
Orally
Administered
Dose
of
Carbaryl,
Technical
Grade,
on
Behavior
and
Neuromorphology
in
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Laboratories,
Ltd.,
Quebec,
Canada.
Study
97389.
Unpublished.
MRID
44069301.
Marshall,
R.
(1996).
Carbaryl:
Induction
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Micronuclei
in
the
Bone
Marrow
of
Treated
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Hazelton
(Europe),
Harrogate,
North
Yorkshire,
England.
Study
No.
198/
89/
1052,
March
13,
1996.
Unpublished.
MRID
44122601.
Robinson,
K
and
B.
Broxup
(1996)
A
13
Week
Study
of
the
Potential
Effects
of
Orally
Administered
Carbaryl,
Technical
Grade,
on
Behavior,
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and
Neuromorphology
in
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Laboratories
Ltd.,
Senneville,
Quebec.
Laboratory
Project
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D.
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September
24,
1996.
43
Unpublished
MRID
44393701.
Robinson,
K.
and
B.
Broxup
(1997)
A
Developmental
Neurotoxicity
Study
of
Orally
Administered
Carbaryl,
Technical
Grade,
in
the
Rat.
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BioResearch,
Ltd.
Quebec,
Canada.
Laboratory
Project
I.
D.
97391,
September
23,
1997.
Unpublished
MRID
No.
44402501.
Totis,
M.
(1997)
Investigation
of
the
Metabolism
of
14
C
Carbaryl
in
the
15
Month
Old
Male
Rat
Following
Chronic
Dietary
Administration.
Final
Report.
Rhone
Poulenc
Agrochimie,
Centre
de
Recherche,
355
rue
Dostoievski,
BP.
153,
F
06903
Sophia
Antipolis,
France.
Study
No.
95288.
Oct.
3,
1997.
Unpublished
MRID
44732901.
Repetto
Larsay,
M.
(1998)
Carbaryl
Developmental
Toxicity
Study
in
the
Rat
by
Gavage.
Rhône
Poulenc
Agro
Centre
de
Recherche,
Sophia
Antipolis,
France.
Study
SA
98070,
October
21,
1998.
Unpublished
MRID
44904202.
Tyl,
RW;
Marr,
MC;
Myers,
CB.
(1999)
Developmental
Toxicity
Evaluation
(with
Cholinesterse
Assessment)
of
Carbaryl
Administered
by
Gavage
to
New
Zealand
White
Rabbits.
Reproductive
&
Developmental
Toxicology
Laboratory,
Center
for
Life
Sciences
and
Toxicology,
Research
Triangle
Park,
NC.
RTI
Identification
No.
65C
7297
200/
100,
June
3,
1999.
Unpublished.
MRID
44904204.
Robinson,
K.
and
Broxup,
B.
(1999)
A
Developmental
Neurotoxicity
Study
of
Orally
Administered
Carbaryl,
Technical
Grade,
in
the
Rat.
ClinTrials
BioResearch
Ltd.,
Senneville,
Quebec,
Canada.
Laboratory
Project
I.
D.
97391,
June
1,
1999.
Unpublished.
MRID
45281801.
Chu
zel
F
(1999).
Carbaryl
6
Month
Carcinogenicity
Study
in
p53
Knockout
Mice
by
Dietary
Administration.
Rhône
Poulenc
Agro
Centre
de
Recherche,
Sophia
Antipolis
Cedex,
France.
Study
Number
SA98155,
July
8,
1999.
Unpublished.
MRID
45281802.
Bigot
D
(1999).
Validation
on
Transgenic
Mice
p53
Knockout
Mice
to
Predict
Rodent
Carcinogenicity.
Rhône
Poulenc
Agro
Centre
de
Recherche,
Sophia
Antipolis
Cedex,
France.
Study
Number
SA97040,
November
10,
1999.
Published
with
the
following
citation:
Carmichael
NG,
Debruyne
EL,
Bigot
Lasserre
D
(2000).
The
p53
heterozygous
knockout
mouse
as
a
model
for
chemical
carcinogenesis
in
vascular
tissue.
Environ
Health
Perspect
108(
1):
61
5.
MRID
45236603.
Dan
ge
M
(1998).
Carbaryl,
Prelimina
ry
28
Day
Toxicity
Study
in
the
Male
TSG
p53
Wild
Type
Mouse
by
Dietary
Administration.
Rhône
Poulenc
Agro
Centre
de
Recherche,
Sophia
Antipolis
Cedex,
France.
Study
Numbers
SA
97499
and
SA
97538,
April
10,
1998.
Unpublished.
MRID
45448101.
Tyl,
R.,
C.
Myers,
M.
Marr.
(2001).
Two
generation
reproductive
toxicity
evaluation
of
carbaryl
(RPA007744)
administered
in
the
feed
to
CD
®
(Sprague
Dawley)
rats.
Reproductive
and
Developmental
Laboratory,
Center
for
Life
Sciences
and
Toxicology,
Chemistry
and
Life
Sciences,
Research
Triangle
Institute,
Life
Sciences
and
Toxicology,
Research
Triangle
Park,
NC
27709.
Laboratory
report
number
65C
07407
400,
May
24,
2001.
Unpublished.
44
MRID
45456701.
Robinson
K,
and
Broxup
B.
(2001)
Final
Report
Amendment
No.
2
Supplement
to
MRID
44393701
A
Developmental
Neurotoxicity
Study
of
Orally
Administered
Carbaryl,
Technical
Grade,
in
the
Rat.
ClinTrials
BioResearch
Ltd.,
Quebec,
Canada.
Laboratory
Project
I.
D.
97391.
July
10,
2001.
Unpublished.
MRID
45456702.
Hamelin
N,
Yipchuck
G.
(2001)
Morphometric
Evaluation
of
Rat
Brain
Areas
for
Developmental
Neuropathology.
ClinTrials
Bioresearch
Ltd.,
Quebec,
Canada.
Laboratory
Project
I.
D.
99579.
July
9,
2001.
Unpublished.
MRID
45456703.
Robinson
K,
and
Broxup
B.
(2001)
Final
Report
Amendment
No.
1
Supplement
to
MRID
44393701
A
Developmental
Neurotoxicity
Study
of
Orally
Administered
Carbaryl,
Technical
Grade,
in
the
Rat.
ClinTrials
BioResearch
Ltd.,
Quebec,
Canada.
Laboratory
Project
I.
D.
97391.
July
6,
2001.
Unpublished.
MRID
45630601.
Austin,
E.
W.
(2002).
4
Week
Repeated
Dose
Dermal
Toxicity
Study
with
Carbaryl
Technical
in
Rats.
Covance
Laboratories,
Madison,
WI.
Laboratory
Study
Identification
Number
6224
268,
March
8,
2002.
Unpublished.
MRID
45630602.
Austin,
E.
W.
(2002).
4
Week
Repeated
Dose
Dermal
Toxicity
Study
with
SEVIN®
XLR
Plus
in
Rats.
Covance
Laboratories,
Madison,
WI.
Laboratory
Study
Identification
Number
6224
267,
March
7,
2002.
Unpublished.
MRID
45630603.
Austin,
E.
W.
(2002).
4
Week
Repeated
Dose
Dermal
Toxicity
Study
with
SEVIN®
80S
in
Rats.
Covance
Laboratories,
Madison,
WI.
Laboratory
Study
Identification
Number
6224
266,
March
8,
2002.
Unpublished.
45
9.0
APPENDICES
Tables
for
Use
in
Risk
Assessment
46
9.1
Toxicity
Profile
Summary
Tables
9.1.1
Acute
Toxicity
Table
See
Section
4.1
9.1.2
Subchronic,
Chronic
and
Other
Toxicity
Tables
Table
1:
Toxicology
Profile
of
Carbaryl
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
870.3100
90
Day
oral
toxicity
rodents
N/
A
870.3150
90
Day
oral
toxicity
in
nonrodents
N/
A
870.3200
21/
28
Day
dermal
toxicity
with
technical
carbaryl
45630601(
2002)
acceptable/
nonguideline
0,
20,
50,
100
mg/
kg/
day
systemic
NOAEL
=
20
mg/
kg/
day
systemic
LOAEL
=
50
mg/
kg/
day
based
on
decreased
RBC
cholinesterase
in
males
and
females
and
brain
cholinesterase
in
males
dermal
NOAEL
=
100
mg/
kg/
day
dermal
LOAEL
not
established
870.3200
21/
28
Day
dermal
toxicity
with
Sevin®
XLR
Plus
(44.82%
a.
i.)
45630602
(2002)
unacceptable/
nonguideline
0,
20,
50,
100
mcL/
kg/
day
(0,
9.6,
24,
48
mg/
kg/
day)
systemic
NOAEL
=
50
mcL/
kg/
day
(24
mg/
kg/
day)
systemic
LOAEL
=
100
mcL/
kg/
day
(48
mg/
kg/
day)
based
on
decreased
body
weight
gain
dermal
NOAEL
=
100
mcL/
kg/
day
(48
mg/
kg/
day)
dermal
LOAEL
not
established
870.3200
21/
28
Day
dermal
toxicity
with
Sevin®
80S
(80.07%
a.
i.)
45630603
(2002)
unacceptable/
nonguideline
0,
20,
50,
100
mg/
kg/
day
systemic
NOAEL
=
20
mg/
kg/
day
systemic
LOAEL
=
50
mg/
kg/
day
based
on
decreased
RBC
cholinesterase
in
males
and
females
dermal
NOAEL
=
100
mg/
kg/
day
dermal
LOAEL
not
established
870.3250
90
Day
dermal
toxicity
N/
A
870.3465
90
Day
inhalation
toxicity
N/
A
870.3700a
Prenatal
developmental
in
rats
44732901
(1998)
acceptable/
guideline
0,
1,
4,
30
mg/
kg/
day
(oral
gavage)
Maternal
NOAEL
=
4
mg/
kg/
day
LOAEL
=
30
mg/
kg/
day
based
on
clinical
signs,
decreased
body
weight
gain
(BWG)
and
food
consumption
Developmental
NOAEL
=
4
mg/
kg/
day
LOAEL
=
30
mg/
kg/
day
based
on
decreased
fetal
body
weight
and
incomplete
ossification
of
multiple
bones
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
47
870.3700b
Prenatal
developmental
in
rabbits
44904202
(1999)
Acceptable/
guideline
0,
5,
50,
150
mg/
kg/
day
(oral
gavage)
Maternal
NOAEL
=
5
mg/
kg/
day
LOAEL
=
50
mg/
kg/
day
based
on
decreased
BWG
and
plasma
cholinesterase
inhibition
(ChEI)
Developmental
NOAEL
=
50
mg/
kg/
day
LOAEL
=
150
mg/
kg/
day
based
on
decreased
fetal
weight
870.3800
Reproduction
and
fertility
effects
45448101
(2001)
acceptable/
guideline
0,
75,
300,
1500
ppm
(4.67,
31.34,
and
92.43
mg/
kg/
day
for
F0
males;
0,
5.56,
36.32,
and
110.78
mg/
kg/
day
for
F0
females;
0,
5.79,
23.49,
and
124.33
mg/
kg/
day
for
F1
males;
and
0,
6.41,
26.91,
and
135.54
mg/
kg/
day
for
F1
females
averaged
over
the
premating
period)
Parental
NOAEL
=
300
ppm
(23.49
31.34
mg/
kg/
day
for
males
and
26.91
36.32
mg/
kg/
day
for
females)
Parental
LOAEL
=
1500
ppm
(92.43
124.33
mg/
kg/
day
for
males
and
110.78
135.54
mg/
kg/
day
for
females)
based
on
decreased
body
weight,
weight
gain,
and
feed
consumption
Reproductive
toxicity
NOAEL
is
$
1500
ppm
(92.43
124.33
mg/
kg/
day
for
males
and
110.78
135.54
mg/
kg/
day
for
females)
Reproductive
toxicity
LOAEL
not
be
established
Offspring
NOAEL
=
75
ppm
(4.67
5.79
mg/
kg/
day
for
males
and
5.56
6.41
mg/
kg/
day
for
females).
Offspring
LOAEL
=
300
ppm
(23.49
31.34
mg/
kg/
day
for
males
and
26.91
36.32
mg/
kg/
day
for
females)
based
on
increased
numbers
of
F2
pups
with
no
milk
in
the
stomach
and
decreased
pup
survival.
870.4100a
Chronic
toxicity
in
rodents
N/
A
870.4100b
Chronic
toxicity
in
dogs
40166701
(1987)
0,
125,
400,
1250
ppm
(0,
3.1,
10,
31.3
mg/
kg/
day)
42022801
(1991)
0,
20,
45,
125
ppm
(5
weeks)
(M:
0,
0.59,
1.43,
3.83;
F:
0,
0,64,
1.54,
4.11
mg/
kg/
day)
Together,
the
studies
are
Acceptable/
guideline
MRID
40166701:
NOAEL
=
not
established
in
females
LOAEL
=
125
ppm
based
based
on
plasma
and
brain
ChEI
MRID
42022801:
NOAEL
=
45
ppm
in
males
LOAEL
=
125
ppm
in
males
based
on
plasma
ChEI
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
48
870.4200
Carcinogenicity
in
mice
42786901
(1993)
Acceptable/
guideline
0,
100,
1000
or
8000
ppm
(M:
0,
14.73,
145.99,
1248.93
mg/
kg/
day;
F:
0,
18.11,
180.86,
1440.62)
systemic
LOAEL
=
1000
ppm
based
on
increased
intracytoplasmic
droplets
in
bladder
in
males
and
females,
chronic
progressive
nephropathy
in
males;
NOAEL
=
100
ppm
RBC
ChEI
LOAEL
for
males
=
1000
ppm
,
for
females
=
8000
ppm;
NOAEL
=
100
ppm
for
males,
1000
ppm
for
females
plasma
ChEI
for
males
and
females
LOAEL
>
8000
ppm;
NOAEL
$
8000
ppm
brain
ChEI
for
males
and
females
LOAEL
=
8000
ppm;
NOAEL
=
1000
ppm
increase
in
vascular
tumors
in
all
treated
males
and
in
females
at
8000
ppm
increase
in
adenomas,
multiple
adenomas,
carcinomas
of
kidney
in
males
at
8000
ppm
increase
in
hepatic
neoplasms
(adenomas,
carcinomas,
one
hepatoblastoma)
in
females
at
8000
ppm
870.4300
Chronic
Toxicity/
Carcinogenicity
in
rats
42918801
(1993)
Acceptable/
guideline
0,
250,
1500
&
7500
ppm
(M:
0,
10,
60.2,
349.5
mg/
kg/
day;
F:
0,
12.6,
78.6,
484.6
mg/
kg/
day)
systemic
LOAEL
=
1500
ppm
in
females
based
on
decreased
BW
and
BWG;
7500
ppm
in
males
based
on
increased
clinical
signs,
decreased
BW,
BWG
and
food
consumption,
increase
in
cataracts,
clinical
pathology
changes,
organ
weight
changes,
nonneoplastic
changes;
NOAEL
=
250
ppm
in
females
and
1500
ppm
in
males
plasma
ChEI
LOAEL
=
7500
ppm
in
males
and
females;
NOAEL
=
1500
ppm
RBC
ChEI
LOAEL
=
1500
ppm
in
males
and
females;
NOEL
=
250
ppm
brain
ChEI
LOAEL
=
7500
ppm
in
males
and
females;
NOEL
=
1500
ppm
at
7500
ppm,
increase
in
liver
adenomas
in
females,
increase
in
benign
transitional
cell
papillomas
and
transitional
cell
carcinomas
in
males
and
females,
transitional
cell
carcinoma
in
kidney
of
one
male,
increase
in
benign
thyroid
follicular
cell
adenomas
in
males,
follicular
cell
carcinoma
in
one
male
Bacterial
reverse
mutation
test
870.5100
41370303
(1989)
Acceptable/
guideline
5
1000
ug/
plate
No
evidence
of
mutagenicity
in
strains
TA1535,
TA
1537,
TA1538,
TA98
and
TA100
with
and
without
metabolic
activation
In
vitro
mammalian
chromosome
aberration
test
(Chinese
hamster
ovary
cells)
870.5385
41370304
(1989)
Acceptable/
guideline
without
S9
activation:
5
100
ug/
mL,
harvest
at
20
hrs.;
with
S9
activation:
25
300
ug/
mL,
harvest
at
30
hrs
Increase
in
chromosome
aberrations
with
S9
activation
In
vitro
mammalian
chromosome
aberration
test
870.5385
41370302;
41420201
(1989)
Unacceptable/
guideline
S9
activation:
1
300
ug/
mL
in
3
trials;
without
S9
activation:
1
300
ug/
mL
in
2
trials
Results
provide
no
clear
indication
of
a
mutagenic
response,
however
study
had
several
deficiencies
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
49
Mammalian
erythrocyte
micronucleus
test
870.
5395
44069301
(1996)
Unacceptable/
guideline
single
oral
gavage
dose
of
50,
100,
200
mg/
kg
Carbaryl
did
not
induce
a
clastogenic
or
aneugenic
effect,
however
there
was
no
convincing
evidence
that
MTD
was
achieved
Unscheduled
DNA
synthesis
870.5550
41370301;
41810601
(1989)
Acceptable/
guideline
0.5
25.0
ug/
mL
Negative
870.6200a
Acute
neurotoxicity
screening
battery
in
rats
MRID:
43845201
43845204
(1995)
Acceptable/
guideline
0,
10,
50,
125
mg/
kg
(oral
gavage)
Separate
study
for
ChE:
0,
10,
30,
50
mg/
kg;
ChE
done
1,
8,
24,
48
hrs
post
dosing
Systemic
LOAEL
=
10
mg/
kg
based
on
decreased
RBC,
plasma,
blood,
brain
ChE;
NOAEL
<
10
mg/
kg
870.6200b
Subchronic
neurotoxicity
screening
battery
in
rats
MRID:
44122601
(1996)
Acceptable/
guideline
0,
1,
10,
30
mg/
kg/
day
(oral
gavage)
LOAEL
for
neurotoxicity
=
10
mg/
kg/
day
based
on
increased
FOB
changes;
NOAEL
=
1
mg/
kg/
day
LOAEL
for
ChEI
=
10
mg/
kg/
day
based
on
decreased
plasma,
blood,
RBC,
brain
ChE;
NOAEL
=
1
mg/
kg/
day
870.6300
Developmental
neurotoxicity
in
rats
44393701
(1997)
Acceptable/
guideline
0,
0.1,
1.0,
10
mg/
kg
(oral
gavage)
Maternal
NOAEL
=
1.0
mg/
kg/
day
LOAEL
=
10
mg/
kg/
day
based
on
decreased
BWG;
FOB
changes;
RBC,
plasma,
whole
blood,
brain
ChEI
Offspring
tentative
NOAEL
=
1.0
mg/
kg/
day
tentative
LOAEL
=
10
mg/
kg/
day
based
on
alterations
in
morphometric
measurements
(measurements
were
not
done
at
lower
doses)
870.7485
Metabolism
and
pharmacokinetics
in
rats
43332101
(1994)
Acceptable/
guideline
1
mg/
kg
(single
and
repeated
oral
doses;
intravenous
dose)
and
50
mg/
kg
(single
oral
dose)
Absorption
was
complete
at
all
doses.
At
168
hrs.,
post
dose,
negligible
percentages
of
dose
in
any
tissues.
Kidney
and
blood
contained
highest
concentrations
of
radioactivity.
Excretion
mostly
through
urine.
A
metabolic
scheme
with
conjugated
and
nonconjugated
metabolites
was
proposed.
870.7485
Metabolism
and
pharmacokinetics
in
rats
44402501
(1997)
Acceptable/
nonguideline
50
mg/
kg
(single
oral
radiolabeled
dose);
daily
oral
radiolabeled
dose
of
2
mg/
kg
for
7
days
followed
by
83
daily
unlabeled
doses
of
0,
250,
1500
or
7500
ppm;
males
only
In
all
dosing
regimens,
urinary
and
fecal
excretion
was
93
103%
of
administered
dose
and
tissue
levels
of
radioactivity
were
minimal
at
168
hrs.
post
dosing.
Two
major
metabolites
in
tissues
at
6
hrs.
post
dosing
were
naphthyl
sulfate
and
naphthyl
glucuronide,
however
quantitation
was
not
possible.
A
total
of
23
and
20
components
were
identified
in
the
urine
and
feces,
respectively.
The
sulfate
conjugation
pathway
appears
to
be
saturable
following
a
83
day
feeding
at
7500
ppm.
BW
and
food
consumption
were
decreased
at
7500
ppm.
Increases
in
kidney,
spleen
and
thyroid
weights
were
observed
at
1500
and
7500
ppm.
Non
neoplastic
changes
in
liver,
thyroids
and
kidneys
were
observed
at
7500
ppm.
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
50
870.7600
Dermal
penetration
in
rats
43552901
(1995)
43.9%
a.
i.
Acceptable
35.6,
403,
3450
ug/
cm
2
%
absorbed
at
10
hrs.:
12.7,
7.44
and
1.93
at
35.6,
403
and
3450
ug/
cm
2
,
respectively
870.7600
Dermal
penetration
in
rats
43339701
(1994)
80.1%
a.
i.
Acceptable
63,
626,
3410
ug/
cm
2
%
absorbed
at
10
hrs:
8.90,
0.62
and
0.48
at
63,
626
and
3410
ug/
cm
2
,
respectively
Special
studies
in
mice
43282201
(1994)
Acceptable/
nonguideline
male
mice:
single
radiolabeled
dose
of
75
mg/
kg;
pretreatment
with
8000
ppm
unlabeled
carbaryl
for
2
wks.,
then
single
radiolabeled
dose
of
75
mg/
kg
Negative
for
DNA
binding
in
liver
Special
studies
in
mice
43832601
(1994)
Acceptable/
nonguideline
continuation
of
MRID
43282201
in
liver
from
mice
treated
at
8000
ppm,
increase
in
microsomal
protein,
cytochrome
P450,
ethoxyresorufin
O
deethylase,
pentoxyresorufin
O
depentylase,
and
testosterone
hydrolases
indicates
phenobarbital
type
of
induction
of
metabolizing
enzymes
Special
study
in
mice
45281801,
45281802,
45236603
(1998
1999)
Acceptable/
nonguideline
0,
10,
30,
100,
300,
1000
and
4000
ppm
(0,
1.8,
5.2,
17.5,
51.2,
164.5
and
716.6
mg/
kg/
day)
There
was
no
evidence
of
neoplastic
or
preneoplastic
changes
in
vascular
tissue
in
heterozygous
p53
deficient
male
mice
treated
with
carbaryl
for
six
months.
N/
A
Not
Available
51
9.2
Summary
of
Toxicological
Dose
and
Endpoints
for
CARBARYL
for
Use
in
Human
Risk
Assessment
1
Table
2:
Summary
of
Toxicology
Endpoint
Selection
for
Carbaryl
Exposure
Scenario
Dose
(mg/
kg/
day)
UF
/MOE
Hazard
Based
Special
FQPA
Safety
Factor
Endpoint
for
Risk
Assessment
Dietary
Risk
Assessments
Acute
Dietary
general
population
including
infants
and
children
NOAEL
=
1
UF
=
100
Acute
RfD
=
0.01
mg/
kg/
day
1
Developmental
Neurotoxicity
rat
LOAEL
=
10
mg/
kg/
day
based
on
an
increased
incidence
of
FOB
changes
on
the
first
day
of
dosing
in
maternal
animals
Chronic
Dietary
all
populations
LOAEL=
3.1
UF
=
300
Chronic
RfD
=
0.01
mg/
kg/
day
1
Chronic
toxicity
dog
LOAEL
=
3.1
mg/
kg/
day
based
on
plasma
and
brain
cholinesterase
inhibition
in
females.
Incidental
Oral
Short
Term
(1
30
Days)
Residential
Only
NOAEL=
1
MOE=
TBD
1
Developmental
Neurotoxicity
rat
LOAEL
=
10
mg/
kg/
day
based
on
an
increased
incidence
of
FOB
changes
and
decreases
in
RBC,
whole
blood,
plasma
and
brain
cholinesterase
Incidental
Oral
Intermediate
Term
(1
6
Months)
Residential
Only
NOAEL=
1
MOE
=
TBD
1
Subchronic
Neurotoxicity
rat
LOAEL
=
10
mg/
kg/
day
based
on
increased
incidence
of
FOB
changes;
decrease
in
RBC,
whole
blood,
plasma
and
brain
cholinesterase.
Exposure
Scenario
Dose
(mg/
kg/
day)
UF
/MOE
Hazard
Based
Special
FQPA
Safety
Factor
Endpoint
for
Risk
Assessment
52
Non
Dietary
Risk
Assessments
Dermal
Short
Term
(1
30
days)
Dermal
NOAEL=
20
4
week
dermal
toxicity
rat
systemic
LOAEL
=
50
mg/
kg/
day
based
on
statistically
significant
decreases
in
RBC
cholinesterase
in
males
and
females
and
brain
cholinesterase
in
males.
Residential
MOE
=
TBD
1
Occupational
100
1
Dermal
Intermediate
Term
(1
6
Months)
Dermal
NOAEL=
20
4
week
dermal
toxicity
rat
systemic
LOAEL
=
50
mg/
kg/
day
based
on
statistically
significant
decreases
in
RBC
cholinesterase
in
males
and
females
and
brain
cholinesterase
in
males.
Residential
MOE
=
TBD
1
Occupational
100
1
Dermal
Long
Term
a
(>
6
Months)
Oral
NOAEL=
3.1
Chronic
toxicity
dog
LOAEL
=
3.1
mg/
kg/
day
based
on
plasma
and
brain
cholinesterase
inhibition
in
females.
Residential
MOE
=
TBD
1
Occupational
300
1
Inhalation
Short
Term
b
(1
30
days)
Oral
NOAEL=
1
Developmental
Neurotoxicity
rat
LOAEL
=
10
mg/
kg/
day
based
on
an
increased
incidence
of
FOB
changes
and
statistically
significant
decreases
in
RBC,
whole
blood,
plasma
and
brain
cholinesterase
Residential
MOE
=
TBD
1
Occupational
100
1
Inhalation
Intermediate
Term
b
(1
6
Months)
Oral
NOAEL=
1
Subchronic
Neurotoxicity
rat
LOAEL
=
10
mg/
kg/
day
based
on
increased
incidence
of
FOB
changes;
decrease
in
RBC,
whole
blood,
plasma
and
brain
cholinesterase.
Residential
MOE
=
TBD
1
Occupational
100
1
Inhalation
Long
Term
b
(>
6
Months)
Oral
NOAEL=
3.1
Chronic
toxicity
dog
LOAEL
=
3.1
mg/
kg/
day
based
on
plasma
and
brain
cholinesterase
inhibition
in
females.
Exposure
Scenario
Dose
(mg/
kg/
day)
UF
/MOE
Hazard
Based
Special
FQPA
Safety
Factor
Endpoint
for
Risk
Assessment
53
Residential
MOE
=
TBD
1
Occupational
300
1
Cancer
Classification:
Q1*
=
8.75
x
10
4
a
Since
an
oral
NOAEL/
LOAEL
was
selected,
a
dermal
absorption
factor
of
12.7%
should
be
used
in
route
to
route
extrapolation.
b
Since
an
oral
NOAEL
was
selected,
an
inhalation
factor
of
100%
should
be
used
in
route
to
route
extrapolation.
TBD
=
To
Be
Determined.
Target
MOEs
for
residential
exposures
will
be
determined
by
the
FQPA
Safety
Factor
Committee.
| epa | 2024-06-07T20:31:42.308529 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0008/content.txt"
} |
EPA-HQ-OPP-2002-0138-0009 | Supporting & Related Material | "2002-07-31T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
Office
of
Prevention,
Pesticides
and
Toxic
Substances
TXR
NO.
0050533
DATE:
March
5,
2002
MEMORANDUM
SUBJECT:
Carbaryl
5
th
Report
of
the
Hazard
Identification
Assessment
Review
Committee.
FROM:
Virginia
A.
Dobozy,
VMD,
MPH
Reregistration
Branch
I,
Health
Effects
Division
(7509C)
THROUGH:
Jess
Rowland,
Co
Chair
and
Elizabeth
Doyle,
Co
Chair
Hazard
Identification
Assessment
Review
Committee
Health
Effects
Division
(7509C)
TO:
Jeff
Dawson,
Risk
Assessor
Reregistration
Branch
I,
Health
Effects
Division
(7509C)
PC
Code:
056801
On
February
19,
2002,
the
Health
Effects
Division
(HED)
Hazard
Identification
Assessment
Review
Committee
(HIARC)
reevaluated
CARBARYL
with
regard
to
the
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
CARBARYL
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996.
The
toxicological
endpoints
used
for
acute
and
chronic
Reference
Doses
(RfDs)
and
occupational/
residential
risk
assessments
were
also
re
evaluated.
New
data,
including
a
multi
generation
reproduction
study
in
rats
and
revised
brain
morphometric
measurements
from
the
developmental
neurotoxicity
study
in
rats,
were
reviewed.
Previous
HIARC
meetings
were
on
July
7,
1998,
April
6,
1999,
November
2,
1999
and
March
1,
2001.
The
conclusions
drawn
at
this
meeting
are
presented
in
this
report.
2
Committee
Members
in
Attendance
Members
present
were:
Ayaad
Assaad,
William
Burnam,
Paula
Deschamp,
Elizabeth
Doyle,
Virginia
Fornillo,
John
Liccione,
Elizabeth
Mendez,
David
Nixon,
Jess
Rowland
Member(
s)
in
absentia:
Pamela
Hurley
Data
evaluation
prepared
by:
Virginia
A.
Dobozy,
VMD,
MPH
Also
in
attendance
were:
Jeff
Dawson
(HED),
Felicia
Fort
(HED),
Michael
Metzger
(HED),
Anthony
Britten
(SRRD)
Data
Evaluation
/
Report
Presentation
Virginia
A.
Dobozy,
VMD,
MPH
Toxicologist
1
Significant
changes
in
some
of
the
brain
morphometric
measurements
were
observed
in
offspring
at
the
high
dose;
only
control
and
high
dose
groups
were
examined.
EPA
requested
that
measurements
be
done
in
the
low
and
mid
dose
groups.
The
registrant
responded
that
the
requested
examinations
were
not
possible
because
the
tissues
of
the
low
and
mid
dose
animals
had
been
stored
in
a
fixative
for
two
years,
which
caused
shrinkage.
Therefore,
comparison
to
the
control
group,
which
was
not
similarly
stored,
would
not
be
valid.
A
re
examination
of
the
control
and
high
dose
groups
was
conducted.
The
re
assessment
uncovered
errors
in
some
measures
and
confirmed
some
of
the
original
findings.
The
additional
statistical
analyses,
which
attempted
to
account
for
multiple
comparisons,
rendered
far
fewer
statistically
significant
findings,
but
some
results,
including
data
on
pup
cerebellar
length,
remained
statistically
significant.
The
decrease
in
the
length
of
the
cerebellum
in
10
mg/
kg/
day
female
pups
was
still
regarded
as
a
treatment
related
effect.
The
NOAEL/
LOAEL
for
this
study
was
originally
regarded
as
tentative,
awaiting
information
from
the
registrant.
Since
morphometric
examinations
of
the
mid
dose
group
were
impossible,
there
remained
some
uncertainty
about
the
NOAEL/
LOAEL.
3
1.
INTRODUCTION
The
toxicology
data
base
on
carbaryl
has
been
evaluated
by
the
HIARC
on
four
occasions
as
described
below.
°.
On
July
7,
1998,
the
HIARC
evaluated
the
data
base,
reassessed
the
RfD
established
in
1994
and
selected
endpoints
for
the
acute
dietary
as
well
as
occupational/
residential
risk
assessments.
At
the
time
of
that
evaluation,
the
data
base
was
incomplete.
There
were
no
acceptable
developmental
or
reproduction
studies
(July
7,
1998
report).
°
At
the
April
6,
1999
meeting,
a
recently
submitted
rat
developmental
study
was
considered.
The
HIARC
concluded
that
there
was
no
basis
to
amend
the
10X
FQPA
Safety
Factor
as
there
were
still
critical
data
gaps,
i.
e.,
no
acceptable
rabbit
developmental
study
or
reproduction
study
(April
28,
1999
report).
°
At
the
November
2,
1999
meeting
of
the
HIARC,
the
FQPA
Safety
Factor
was
again
reconsidered
with
the
submission
of
an
acceptable
rabbit
developmental
study.
The
Committee
concluded
that,
based
on
the
satisfaction
of
the
rat
and
rabbit
developmental
study
data
requirements
in
which
there
was
no
fetal
susceptibility,
the
FQPA
Safety
Factor
recommendation
could
be
reduced
from
10X
to
3X
(November
15,
1999
report).
At
the
November
29,
1999
meeting
of
the
FQPA
Safety
Factor
Committee,
it
was
concluded
that
the
10X
safety
factor
should
be
retained
because:
1)
the
toxicology
data
base
was
incomplete,
i.
e.,
lack
of
reproduction
study;
2)
an
assessment
of
susceptibility
following
pre/
post
natal
exposure
to
carbaryl
could
not
be
made
due
to
the
data
gaps
for
the
reproduction
study;
3)
there
was
concern
for
the
results
of
the
developmental
neurotoxicity
study.
1
The
Committee
concluded
that
the
10X
Safety
Factor
should
be
applied
to
acute
and
chronic
dietary
exposures
and
residential
(nonoccupational)
exposures
(December
13,
1999
report).
°
On
March
1,
2001,
the
HIARC
reevaluated
carbaryl
with
regard
to
the
acute
and
chronic
Reference
Doses
(RfDs)
and
the
toxicological
endpoint
selection
for
use
in
occupational/
residential
exposure
risk
assessments
(April
5,
2001
report).
On
April
16,
2001,
the
FQPA
Safety
Factor
Committee
again
confirmed
that
the
10x
factor
should
be
retained
based
on
the
same
criteria
as
described
at
the
4
November
29,
1999
meeting
(April
30,
2001
report).
The
February
19,
2002
meeting
was
convened
to
discuss
the
following
issues:
1)
A
multi
generation
reproduction
study
(MRID
45448101)
has
been
submitted
and
evaluated.
There
is
evidence
of
offspring
susceptibility.
The
LOAEL
for
parental
systemic
toxicity
was
1500
ppm
(92.43
124.33
mg/
kg/
day
for
males
and
110.78
135.54
mg/
kg/
day
for
females)
based
on
decreased
body
weight,
weight
gain,
and
feed
consumption.
The
NOAEL
was
300
ppm
(23.49
31.34
mg/
kg/
day
for
males
and
26.91
36.32
mg/
kg/
day
for
females).
The
LOAEL
for
offspring
toxicity
was
300
ppm
(23.49
31.34
mg/
kg/
day
for
males
and
26.91
36.32
mg/
kg/
day
for
females)
based
on
increased
numbers
of
F2
pups
with
no
milk
in
the
stomach
and
decreased
pup
survival.
The
NOAEL
was
75
ppm
(4.67
5.79
mg/
kg/
day
for
males
and
5.56
6.41
mg/
kg/
day
for
females).
The
HIARC
was
requested
to
consider
how
the
study
results
affect
the
determination
of
fetal/
offspring
susceptibility
and
the
Special
FQPA
Safety
Factor
recommendation.
2)
The
registrant
has
conducted
new
brain
morphometric
measurements
of
the
control
and
high
dose
animals
from
the
developmental
neurotoxicity
study.
In
prior
reviews,
HED
concluded
that
there
was
a
significant
increase
in
the
thickness
of
the
right
forebrain
in
male
pups
and
a
significant
decrease
in
the
left
forebrain
of
adult
males.
The
new
submission
reanalyzed
the
combined
(left
and
right)
data
on
the
forebrain
(Line
B)
in
male
pups
and
the
forebrain
(Line
A)
in
adult
males.
Based
on
a
statistical
analysis
of
combined
(left
and
right)
forebrain
measurements,
there
was
no
difference
from
controls
in
both
pups
and
adults.
However,
HED's
statistical
analysis
found
a
decrease
in
the
size
of
the
forebrain
in
adult
males.
In
prior
reviews,
HED
concluded
that
there
was
a
statistically
significant
bilateral
decrease
in
the
length
of
the
cerebellum
(Line
F)
of
female
pups
and
a
statistically
significant
bilateral
increase
in
the
width
of
the
cerebellum
(Line
G)
of
adult
females.
The
new
submission
contains
measurements
of
different
layers
of
the
cerebellum
in
pups
and
adults.
There
were
no
statistically
significant
differences
between
treated
and
control
animals.
HED
concluded
that
these
measurements
of
individual
cell
layers
do
not
negate
the
original
findings
in
the
cerebellum
of
female
pups
and
adults.
The
HIARC
was
requested
to
consider
how
these
revisions
affect
the
determination
of
fetal/
offspring
susceptibility
and
the
Special
FQPA
Safety
Factor
recommendation.
3)
At
the
March
1,
2001
HIARC
meeting,
the
endpoint
selection
for
occupational/
residential
(ORE)
risk
assessments
was
based
on
current
duration
of
exposure
definitions,
which
have
been
changed
(June
4,
2001
Memorandum
from
HED
Division
Director).
The
registrant
has
conducted
4
week
dermal
exposure
studies
(one
with
technical
and
two
with
formulations);
however,
they
have
not
been
submitted.
RRB1
is
proposing
to
maintain
the
endpoints
selected
for
the
ORE
exposures
at
the
March
1
meeting
until
the
dermal
studies
have
been
submitted
and
reviewed.
The
HIARC
concluded
that
the
occupational/
residential
durations
used
for
the
risk
assessment
at
the
March
1,
2001
meeting
should
be
maintained
until
the
dermal
exposure
studies
have
been
submitted
and
evaluated.
The
following
document
includes
the
endpoint
selection
and
FQPA
considerations
from
the
February
19,
2001
meeting
and
cancer
reclassification
(November
7,
2001
meeting
of
the
Cancer
Assessment
Review
Committee).
2.
HAZARD
IDENTIFICATION
5
2.1
Acute
Reference
Dose
(RfD)
General
Population
Study
Selected:
Developmental
Neurotoxicity
Study
in
Rats
§81
8;
OPPTS
870.6300
MRID
Nos.:
44393701,
45456701,
45456702,
45456703
Executive
Summary:
In
a
developmental
neurotoxicity
study
(MRID
#
44393701,
45456701,
45456702,
45456703),
26
pregnant
female
Sprague
Dawley
rats/
group
were
administered
carbaryl
(99.1%
a.
i.)
by
gavage
from
Gestation
Day
(GD)
6
through
Lactation
Day
(LD)
10
at
doses
of
either
0,
0.1,
1.0
or
10
mg/
kg/
day.
An
additional
6
pregnant
females/
group
were
dosed
at
the
same
levels
for
the
cholinesterase
(ChE)
phase
of
the
study.
ChE
measurements
were
done
pre
dosing
(GD
6)
and
post
dosing
at
time
of
peak
effect
(1
hour
post
dosing)
on
GD
6,
15
and
20
and
LD
4
and
10.
Functional
Observational
Battery
(FOB)
measurements
were
performed
at
approximately
0.5
and
2
hours
post
dosing
on
the
same
days
as
body
weight
measurements
during
the
dosing
period
(GD
0,
6,
9,
12,
15,
18
and
20
and
LD
4,
7,
11,
13
and
21).
Measures
of
reproductive
performance
were
evaluated.
Offspring
were
examined
for
body
weight,
physical
development
landmarks
(tooth
eruption
and
eye
opening),
FOB
assessments
(days
4,
7,
11,
13,
17
and
21)
and
motor
activity
(days
13,
17
and
21).
On
LD
11,
1
animal/
sex/
litter
was
sacrificed
for
brain
weights;
of
these,
six/
sex
were
randomly
selected
for
neuropathological
evaluation.
The
eyes
from
all
dose
groups
were
examined.
After
LD
21,
3
animals/
sex/
litter
were
separated
from
the
dams
and
constituted
the
F1
adult
generation.
These
animals
were
evaluated
for
body
weight,
physical
development
(vaginal
opening
and
preputial
separation),
motor
activity
(day
60),
startle
habituation
response
(days
22
and
60),
passive
avoidance
(day
23)
and
water
maze
behavior
(day
60).
After
completion
of
the
behavior
test
period
(at
approximately
10
weeks
of
age),
12
animals/
sex/
group
were
anesthetized
and
perfused
for
post
mortem
examination.
Tissues
from
6
animals/
sex
of
the
control
and
high
dose
group
were
processed
for
neuropathological
evaluation
and
morphometric
measurements;
the
eyes
from
the
low
and
mid
dose
group
of
all
perfused
animals
were
examined.
For
the
F0
generation
animals,
there
were
no
carbaryl
associated
deaths.
No
treatment
related
clinical
signs
of
toxicity
were
observed.
There
was
a
statistically
significant
decrease
(92%)
in
body
weight
gain
for
females
in
the
10
mg/
kg/
day
group
for
the
period
GD
6
9.
Unfortunately,
food
consumption
was
not
measured
during
the
study.
During
the
FOB
measurements,
the
incidence
of
females
in
the
10
mg/
kg/
day
group
with
decreased
pupil
size
(pinpoint
pupils)
was
increased
on
all
occasions
during
the
dosing
period.
An
increased
incidence
of
dams
with
slight
tremors
affecting
the
head,
body
and/
or
limbs
was
noted
on
the
majority
of
assessment
occasions
in
the
dosing
period.
There
were
also
occasional
occurrences
of
ataxic
gait/
overall
gait
in
capacity
which
was
considered
to
be
of
toxicological
significance
due
to
other
effects
upon
gait.
For
the
10
mg/
kg/
day
group,
RBC
and
whole
blood
ChE
levels
were
statistically
significantly
decreased
(28%
and
32
34%,
respectively)
on
GD
20
and
LD
10.
Although
the
plasma
ChE
levels
were
not
statistically
significantly
altered,
the
percentage
decreases
on
GD
20,
LD
4
and
LD
10
were
32
39%.
Brain
ChE
levels
were
statistically
significantly
decreased
(42%).
There
6
were
no
treatment
related
effects
on
gross
necropsy
findings
for
the
F0
generation
animals.
There
were
no
effects
observed
on
maternal
performance
parameters
of
pregnancy
rate,
gestation
index,
length
of
gestation,
numbers
of
live
pups,
dead
or
malformed
pups,
implantation
scars,
sex
ratio
or
post
implantation
loss.
There
was
a
slight
(P>
0.05)
increase
in
the
number
of
dead
pups
in
the
10
mg/
kg/
day
group,
however
the
value
was
within
the
historical
control
range
for
this
strain.
For
the
F1
generation
pups,
there
were
no
treatment
related
effects
on
pup
weight,
pup
survival
indices,
developmental
landmarks
(tooth
eruption
and
eye
opening),
FOB
measurements
or
motor
activity
assessments.
At
sacrifice
on
LD
11,
there
were
no
treatmentrelated
effects
on
brain
weight
and
gross
or
microscopic
pathology.
Significant
differences
noted
in
the
morphometric
measurements
included
an
increase
in
Line
B
of
the
right
forebrain
and
Line
F
of
the
left
cerebellum
in
the
10
mg/
kg/
day
males.
In
the
10
mg/
kg/
day
females,
Line
F
through
both
the
right
and
left
cerebellum
were
significantly
decreased
(15%
and
22%,
respectively).
For
the
F1
generation
adults,
there
were
no
treatment
related
effects
on
clinical
condition,
body
weight,
physical
development
(vaginal
opening
and
preputial
separation),
motor
activity,
auditory
startle
response,
passive
avoidance
and
water
maze
measurements.
At
sacrifice,
there
were
no
gross
or
microscopic
neuropathological
lesions
observed
for
animals
examined
in
this
study
that
were
attributable
to
treatment
with
the
test
article.
There
was
an
increased
incidence
of
retinal
fold/
rosette
in
the
10
mg/
kg/
day
group
(1/
12
for
control
vs.
4/
12
for
males;
0/
12
for
control
vs.
2/
12
for
females).
The
finding
was
not
considered
of
toxicological
significance
since
the
incidence
was
within
the
historical
control
range
for
males,
occurred
at
a
low
rate
and
was
not
dose
dependent.
For
the
morphometric
measurements,
there
was
a
significant
bilateral
decrease
in
Line
A
through
the
forebrain
(7.7
9.8%)
and
a
significant
increase
in
Line
F
through
the
right
cerebellum
of
the
10
mg/
kg/
day
males.
Increases
originally
noted
in
10
mg/
kg
adult
females
in
Line
G,
width
of
the
cerebellum,
were
found
to
be
based
on
erroneous
measurements,
and
additional
measures
were
submitted.
Now,
for
the
10
mg/
kg/
day
females,
there
were
significant
bilateral
increases
in
Line
F
through
the
cerebellum
(7.4
15%).
Measurements
of
the
size
of
the
thickness
of
lobes
and
of
the
granule
cell
layers
of
the
cerebellum
in
high
dose
pups
and
adults
did
not
differ
from
those
of
controls.
While
additional
statistical
analyses
by
the
registrant
indicated
no
treatment
related
effects,
HED's
additional
statisical
analyses
did
indicate
treatment
related
effects.
The
maternal
toxicity
LOAEL
was
10
mg/
kg/
day
based
on
decreased
body
weight
gain,
alterations
in
FOB
measurements
and
RBC,
plasma,
whole
blood
and
brain
cholinesterase
inhibition.
The
maternal
NOAEL
was
1.0
mg/
kg/
day.
The
developmental
neurotoxicity
LOAEL
was
10
mg/
kg/
day
based
on
a
bilateral
decrease
in
the
size
of
the
forebrain
(Line
A)
in
adult
males
(7.7
9.8%);
a
bilateral
decrease
in
the
length
of
the
cerebella
(Line
F)
in
female
pups
(15
22%);
and
a
bilateral
increase
in
the
length
of
the
cerebella
(Line
F)
in
female
adults
(7.4
15%).
The
developmental
NOAEL
was
1
mg/
kg/
day.
Morphometric
assessment
at
the
mid
and
7
low
doses
could
not
be
conducted
due
to
inadequate
tissue
storage;
however,
based
on
the
minimal
findings
at
the
LOAEL,
it
is
HED's
judgment
that
effects
would
be
unlikely
to
occur
at
1
mg/
kg/
day,
which
is
10%
of
the
LOAEL.
Co
critical
Study:
Study
Selected:
Acute
Neurotoxicity
Study
in
Rats
§81
8;
OPPTS
870.6200a
MRID
Nos.:
43845201
43845204
Executive
Summary:
In
an
acute
neurotoxicity
study
(MRID
#
43845204),
groups
of
12
male
and
12
female
Sprague
Dawley
rats
were
administered
carbaryl
technical
grade
in
0.5%
carboxymethylcellulose
/
0.1%
Tween
80
at
doses
of
10,
50,
or
125
mg/
kg/
day.
Doses
were
selected
on
the
basis
of
results
from
a
benchmark
toxicity
study
(MRID
#
43845201)
and
a
"time
of
peak
effects"
study
(MRID
#
43845202).
In
the
benchmark
study,
clinical
signs
of
toxicity
and
body
weight
loss
were
observed
at
50
mg/
kg
and
above,
and
mortality
was
observed
at
500
mg/
kg
and
above.
In
the
time
of
peak
effects
study,
peak
effect
for
cholinesterase
inhibition
and
functional
observational
battery
changes
was
determined
to
be
0.5
to
1.0
hr
post
dose.
Body
weight
was
mildly
but
significantly
decreased
in
male
rats
at
the
125
mg/
kg
dose
level,
while
weight
gain
was
significantly
decreased
in
male
and
female
rats
for
days
0
7
of
the
study
at
125
mg/
kg.
Food
consumption
during
week
1
was
decreased
at
the
125
mg/
kg
dose
by
18
20%,
in
excess
of
the
decrease
in
body
weight
gain,
supporting
a
treatment
related
effect
at
the
high
dose
for
week
1
of
the
study.
Several
measurements
from
Functional
Observational
Battery
assessment
were
significantly
altered
at
the
50
and
125
mg/
kg
dose,
including
an
increased
incidence
of
tremors,
ataxic
gait,
decreased
body
temperature,
and
decreased
arousal.
Salivation
incidence
was
increased
at
the
high
dose,
as
was
hindlimb
splay.
Forelimb
and
hindlimb
grip
strength
were
decreased
significantly
at
the
high
dose.
Significant
decreases
in
total
motor
activity
were
observed
in
male
and
female
rats
at
all
dose
levels
tested.
Significant
inhibition
of
plasma,
blood,
and
brain
cholinesterase
(30
40%)
was
also
observed
in
both
sexes
at
the
10
mg/
kg
dose.
Peak
inhibition
of
cholinesterase
occurred
during
the
time
of
FOB
and
motor
activity
measurements.
Based
on
the
data
in
this
study,
the
systemic
LOAEL
=
10
mg/
kg
for
male
and
female
rats,
based
on
significant
inhibition
of
red
cell,
plasma,
whole
blood,
and
brain
cholinesterase
at
the
10
mg/
kg
dose
level.
The
systemic
NOAEL
<
10
mg/
kg
for
male
and
female
rats.
This
study
is
classified
as
acceptable
and
satisfies
the
guideline
requirement
for
an
acute
neurotoxicity
study
(§
81
8;
OPPTS
870.6200)
in
rats.
Dose
and
Endpoint
for
Establishing
RfD:
Maternal
NOAEL
of
1
mg/
kg
based
on
alterations
in
FOB
parameters
on
the
first
day
of
dosing
at
10
mg/
kg
Uncertainty
Factor
(UF):
100
[10
for
intraspecies
variation
and
10
for
interspecies
variation].
8
Comments
about
Study/
Endpoint/
Uncertainty
Factor:
Previously
(March
1,
2001),
the
HIARC
selected
the
acute
neurotoxicity
study
this
risk
assessment.
However,
upon
reevaluation
and
comparison
of
the
results
of
the
acute
neurotoxicity
and
the
developmental
neurotoxicity
studies,
the
HIARC
determined
that
the
maternal
effects
in
the
developmental
neurotoxicity
study
observed
after
a
single
oral
dose
were
most
appropriate
for
this
risk
assessment.
This
is
also
the
dose
at
which
effects
were
observed
in
offspring;
therefore,
use
of
the
maternal
NOAEL
is
protective
for
infants
and
children.
Additionally,
use
of
the
LOAEL
from
the
acute
neurotoxicity
study
with
a
3x
uncertainty
factor
would
result
in
a
calculated
NOAEL
of
3
mg/
kg/
day
and
an
acute
RfD
of
0.03
mg/
kg.
The
HIARC
determined
that
it
was
more
conservative
and
protective
of
all
populations
(including
females
13
50)
to
use
the
developmental
neurotoxicity
study.
2.2
Chronic
Reference
Dose
(RfD)
Study
Selected:
Chronic
Toxicity
Dog
§
83
1,
OPPTS
870.4100
MRID
Nos.:
40166701,
42022801
Executive
Summary:
In
a
chronic
toxicity
study
(MRID
No.
40166701),
carbaryl
(99%)
was
administered
in
the
diet
to
6
beagle
dogs/
sex/
group
at
doses
of
0,
125,
400
or
1250
ppm
for
one
year.
Nominal
doses
were
3.1,
10
and
31.3
mg/
kg/
day.
There
were
no
deaths
during
the
study.
With
the
1250
ppm
females,
there
was
an
increased
incidence
of
clinical
signs
of
toxicity,
including
emesis,
lacrimation,
salivation
and
tremors.
Mean
body
weight
gain
was
decreased
(50%)
in
the
1250
ppm
females
for
weeks
0
6.
Mean
food
consumption
was
decreased
(16
24%,
not
statistically
significant)
in
the
1250
ppm
females
at
multiple
time
periods
during
the
study.
No
treatment
related
ophthalmoscopic
changes
were
observed.
There
was
a
statistically
significant
increase
in
white
blood
cell
and
segmented
neutrophil
counts
at
some
of
the
testing
intervals
for
the
1250
ppm
group
males.
Albumin
levels
were
significantly
decreased
(9
11%)
at
all
of
the
testing
periods
in
the
1250
ppm
females.
Plasma
cholinesterase
(ChE)
levels
in
males
were
significantly
decreased
in
the
400
ppm
(30
36%
9
)
and
1250
ppm
(58
66%
9
)
groups
at
all
testing
intervals
(weeks
5,
13,
26
and
52).
Plasma
ChE
levels
in
females
were
significantly
decreased
at
most
intervals
in
the
125
ppm
group
(12
23%
9
),
400
ppm
group
(9
31%
9
)
and
1250
ppm
group
(47
60
).
RBC
ChE
levels
in
males
were
significantly
decreased
in
the
400
ppm
group
(23
28%
9
at
weeks
5
and
13)
and
1250
ppm
group
(46
56%
9
for
all
intervals).
RBC
ChE
levels
in
females
were
significantly
decreased
in
the
400
ppm
group
(29
34%
9
at
weeks
5,
13
and
26)
and
1250
ppm
(29
38%
9
for
all
intervals).
Brain
ChE
in
males
was
not
statistically
significantly
decreased
but
biologically
decreased
in
the
400
ppm
group
(32%
9
)
and
1250
ppm
group
(25%
9
).
Brain
ChE
in
females
was
significantly
decreased
(20
36%
9
)
in
all
the
groups.
No
treatment
Acute
RfD
=
1
mg/
kg
=
0.01
mg/
kg
100
9
related
effects
were
seen
in
urinalysis
parameters.
At
necropsy,
there
was
a
statistically
significant
increase
in
the
absolute
weight
of
the
liver/
gall
bladder
in
the
1250
ppm
group
males.
Relative
and
liver
to
brain
weights
were
also
increased
but
not
significantly.
There
was
a
dose
related
decrease
in
the
absolute,
relative
and
organ
to
brain
weights
of
the
pituitary
in
males,
although
none
of
the
changes
was
statistically
significant.
There
was
also
a
significant
decrease
in
the
relative
weight
of
the
thyroid
in
this
group.
However,
since
there
were
no
accompanying
microscopic
changes
in
these
organs,
the
toxicological
significance
of
these
organ
weight
effects
is
questionable.
The
LOAEL
for
systemic
toxicity
was
1250
ppm
(31.3
mg/
kg/
day)
based
on
an
increased
incidence
of
clinical
signs
(females),
decreased
body
weight
and
food
consumption
(females)
and
alterations
in
clinical
pathology
parameters
(both
sexes);
NOAEL
was
400
ppm
(10
mg/
kg/
day).
The
LOAEL
for
plasma
cholinesterase
inhibition
was
125
ppm
(3.1
mg/
kg/
day)
for
females;
a
NOAEL
was
not
established.
The
LOAEL
for
plasma
cholinesterase
inhibition
was
400
ppm
(10
mg/
kg/
day)
for
males;
the
NOAEL
was
125
ppm
(3.1
mg/
kg/
day).
The
LOAEL
for
RBC
cholinesterase
inhibition
was
400
ppm
(10
mg/
kg/
day)
for
males
and
females;
the
NOAEL
was
125
ppm
(3.1
mg/
kg/
day).
The
LOAEL
for
brain
cholinesterase
inhibition
was
125
ppm
(3.1
mg/
kg/
day)
for
females;
a
NOAEL
was
not
established.
The
LOAEL
for
brain
cholinesterase
inhibition
was
400
ppm
(10
mg/
kg/
day)
for
males;
the
NOAEL
was
125
ppm
(3.1
mg/
kg/
day).
In
a
five
week
study
(MRID
#
42022801)
done
to
upgrade
the
chronic
study,
carbaryl
(99.3%
a.
i.)
was
administered
in
the
diet
to
six
beagles/
sex/
group
at
doses
of
0,
20,
45
or
125
ppm.
Actual
mg/
kg/
day
doses
for
males
were
0,
0.59,
1.43
and
3.83
mg/
kg/
day,
respectively;
doses
for
females
were
0,
0.64,
1.54
and
4.11
mg/
kg/
day,
respectively.
The
following
parameters
were
measured:
clinical
observations,
body
weights,
food
consumption,
ophthalmoscopic
examinations,
plasma
and
RBC
cholinesterase
(at
days
11,
8
and
5
pretest
and
then
days
14
and
32
of
the
study),
brain
cholinesterase
(at
termination)
and
gross
necropsies.
This
study
was
conducted
to
complete
the
information
needed
to
satisfy
the
chronic
toxicity
study
requirement
in
nonrodent
species.
There
were
no
deaths
or
treatment
related
clinical
signs
of
toxicity.
There
were
no
treatmentrelated
effects
on
body
weights,
food
consumption
or
ophthalmoscopic
examinations.
In
males,
there
was
a
statistically
and
biologically
significant
decrease
in
plasma
cholinesterase
for
the
125
ppm
(22%
9
)
group.
The
LOAEL
for
systemic
toxicity
and
for
RBC
and
brain
cholinesterase
inhibition
was
>125
ppm
(males:
3.83
mg/
kg/
day;
females:
4.11
mg/
kg/
day);
the
NOAEL
was
$
125
ppm.
The
LOAEL
for
plasma
cholinesterase
inhibition
for
males
was
125
ppm;
the
NOAEL
was
45
ppm
(1.43
mg/
kg/
day).
The
LOAEL
for
cholinesterase
inhibition
for
females
was
>125
ppm;
10
the
NOAEL
was
$
125
ppm.
Dose
and
Endpoint
for
Establishing
RfD:
LOAEL
=3.1
mg/
kg/
day
based
on
plasma
and
brain
cholinesterase
inhibition
in
females.
Uncertainty
Factor(
s):
300
[10
for
intra
species
variation,
10
for
interspecies
variation
and
3
for
use
of
a
LOAEL].
Comments
about
Study/
Endpoint/
Uncertainty
Factor:
The
HIARC
determined
that
the
LOAEL
from
the
1
year
dog
study
was
appropriate
for
the
following
reasons:
1)
An
additional
uncertainty
factor
of
3X
was
applied
because
of
the
use
of
a
LOAEL
(i.
e.,
lack
of
a
NOAEL
in
a
critical
study).
Although
a
NOAEL
was
not
established
in
this
study,
the
Committee
determined
that
an
additional
factor
of
3X
(as
opposed
to
a
higher
value)
was
adequate
because:
1)
cholinesterase
inhibition
was
not
accompanied
by
clinical
signs;
2)
no
inhibition
was
seen
for
any
cholinesterase
compartment
in
males
at
this
dose;
3)
the
magnitude
of
inhibition
of
plasma
cholinesterase
inhibition
(12
23%
decrease)
was
comparable
to
the
magnitude
of
inhibition
(22%)
seen
in
the
5
week
study
in
dogs
indicating
no
cumulative
effects
following
long
term
exposure;
and
4)
the
study
was
well
conducted
and
there
are
sufficient
data
from
subchronic
and
chronic
duration
studies
in
the
other
species
which
support
cholinesterase
inhibition
as
the
critical
effect
2)
Based
on
the
cholinesterase
inhibition
data,
the
dog
appears
to
be
more
sensitive
than
the
rat
in
long
term
studies.
Male
and
female
rats
treated
at
10
and
13
mg/
kg/
day,
respectively,
of
carbaryl
in
the
diet
for
53
weeks
demonstrated
negligible
plasma,
RBC
and
brain
cholinesterase
inhibition,
whereas
dogs
treated
at
a
comparable
dose
for
the
same
duration
had
inhibition
of
all
three
compartments.
3)
The
HIARC
determined
that
use
of
the
LOAEL
from
the
1
year
study
(plasma
and
brain
cholinesterase
inhibition
in
females)
provided
more
convincing
evidence
of
a
toxicological
effect
than
use
of
the
NOAEL
of
1.43
mg/
kg/
day
based
on
plasma
cholinesterase
inhibition
in
males
from
the
5
week
study.
4)
Use
of
the
LOAEL
from
the
1
year
dog
study
with
an
uncertainty
factor
of
300
results
in
a
chronic
RfD
which
would
be
identical
to
that
derived
if
the
offspring
NOAEL
(1.0
mg/
kg/
day)
from
the
developmental
neurotoxicity
study
was
used
with
an
uncertainty
factor
of
100;
therefore,
infants
and
children
will
also
be
protected
by
using
the
1
year
dog
study.
2.3
Occupational/
Residential
Exposure
2.3.1
Short
Term
(1
7
days)
Incidental
Oral
Exposure
Chronic
RfD
=
3.1
mg/
kg/
day
=
.01
mg/
kg/
day
300
11
Study
Selected:
Developmental
Neurotoxicity
Study
§81
8;
OPPTS
870.6300
MRID
No.:
44393701,
45456701,
45456702,
45456703
Executive
Summary:
See
2.1
Acute
Reference
Dose
(RfD)
General
Population
Dose
and
Endpoint
for
Risk
Assessment:
Maternal
NOAEL
of
1
mg/
kg
based
on
alterations
in
FOB
parameters
on
the
first
day
of
dosing
at
10
mg/
kg
Comments
about
Study/
Endpoint:
The
HIARC
determined
that
study
is
appropriate
for
the
short
term
oral
exposure
time
period
because
effects
(FOB
alterations)
were
observed
after
a
single
dose
and
continued
after
multiple
days
of
dosing
and
are
appropriate
for
the
population
of
concern
(infants
and
children).
Although
a
maternal
NOAEL
was
used,
this
dose
would
be
protective
of
offspring
effects
since
the
NOAEL/
LOAEL
were
the
same
for
offspring
toxicity.
2.3.2
Intermediate
Term
(7
Days
to
Several
Months)
Incidental
Oral
Exposure
Study:
Subchronic
Neurotoxicity
Study
Study
Guideline#:
§
81
8,
OPPTS
870.6200
MRID
No.:
44122601
Executive
Summary:
In
a
subchronic
neurotoxicity
study,
12
Crl:
CD(
SD)
BR
rats/
sex/
group
were
administered
technical
carbaryl
(99.1%)
by
gavage
at
doses
of
0,
1,
10
or
30
mg/
kg/
day
for
13
weeks.
Cholinesterase
(RBC,
whole
blood,
plasma
and
brain)
determinations
were
done
on
an
additional
three
groups
of
five
rats/
sex/
group
at
Weeks
4,
8
and
13.
Neurobehavioral
screening,
consisting
of
Functional
Observational
Battery
(FOB)
and
motor
activity
evaluations,
was
performed
prior
to
treatment
and
during
Weeks
4,
8
and
13.
At
terminal
sacrifice,
six
animals/
sex/
dose
were
anesthetized
and
perfusion
fixed
in
situ
for
neuropathological
evaluation.
There
were
no
deaths
during
the
study.
There
was
an
increased
incidence
of
clinical
signs
of
toxicity,
including
slight
and
moderate
salivation
and
tremors,
in
the
30
mg/
kg/
day
males
and
females.
Body
weight
over
the
course
of
the
study
was
statistically
significantly
decreased
in
the
30
mg/
kg/
day
males
(14%)
and
females
(15%).
Body
weight
gain
for
these
groups
was
decreased
27%
in
males
and
37%
in
females,
compared
to
controls.
Food
consumption
was
decreased
during
most
of
the
study
for
the
30
mg/
kg/
day
males
and
females.
Males
and
females
in
the
30
mg/
kg/
day
group
had
a
statistically
significant
decrease
in
RBC
(M:
42
46%;
F:
52
55%),
whole
blood
(M:
49
51%;
F:
59
63%)
and
plasma
(M:
63
69%;
F:
63
69%)
at
most
of
the
testing
periods.
Males
and
females
in
the
10
mg/
kg/
day
group
had
a
statistically
significant
decrease
in
RBC
(M:
26
38%;
F:
17
24%);
whole
blood
(M:
30
41%;
F:
21
26%)
and
plasma
(M:
43
48%;
F:
23
30%).
There
was
a
statistically
significant
decrease
in
brain
cholinesterase
in
males
and
females
in
the
10
mg/
kg/
day
(M:
27
61%;
F:
20
58%)
and
30
mg/
kg/
day
(M:
36
80%;
F:
50
73%)
groups.
For
the
1
mg/
kg/
day
males,
there
were
12
statistically
significant
decreases
in
whole
blood
(13%)
at
week
13
and
for
plasma
(20%)
at
week
8.
These
changes
are
not
considered
toxicologically
significant
since
they
occurred
infrequently
and
were
relatively
minor
effects.
Multiple
qualitative
and
quantitative
FOB
parameters
were
affected
in
the
10
and
30
mg/
kg/
day
males
and
females,
including
the
following:
slight
tremors,
gait
alterations,
pinpoint
pupils,
increased
salivation,
reduced
extensor
thrust,
decreased
pinna
reflex,
reduced
number
of
rearings,
decreased
vocalizations,
decreased
body
temperature
and
decreased
forelimb
grip.
Reduced
number
of
defecations
was
observed
only
at
30
mg/
kg/
day.
There
was
an
occasional
alteration
at
the
1
mg/
kg/
day
dose.
At
week
8,
males
had
a
very
slight
increase
in
the
incidence
of
pinpoint
pupils
(incidence
in
control,
1,
10
and
30
mg/
kg/
day
groups
was
0/
12,
1/
12,
6/
12
and
10/
12,
respectively).
A
statistically
significant
decrease
in
forelimb
grip
was
observed
at
week
4
in
males
(values
for
control,
1,
10
and
30
mg/
kg/
day
groups
were
1060.8,
943.8,
943.8
and
950.0,
respectively).
The
number
of
defecations
was
statistically
reduced
in
females
at
week
13
(mean
number
of
defecations
in
control,
1,
10
and
30
mg/
kg/
day
groups
were
1.4,
0.2,
0.5
and
0.0,
respectively).
The
toxicological
significance
of
these
effects
is
questionable
since
the
incidence
was
either
low
or
there
was
no
dose
response
relationship.
Motor
activity
was
statistically
significantly
decreased
in
the
30
mg/
kg/
day
males
at
Week
4
and
the
30
mg/
kg/
day
females
at
Weeks
4
and
8.
On
necropsy,
there
was
an
increased
incidence
of
dark
areas
in
the
meninges
of
the
30
mg/
kg/
day
males;
these
animals
had
an
increased
incidence
of
hemorrhage
on
microscopic
examination.
One
female
in
the
30
mg/
kg/
day
group
also
had
retinal
atrophy.
There
were
no
differences
in
brain
length
or
width
measurements.
The
LOAEL
for
neurotoxicity
was
10.0
mg/
kg/
day
based
on
an
increased
incidence
of
FOB
changes;
the
NOAEL
was
1.0
mg/
kg/
day.
The
LOAEL
for
cholinesterase
inhibition
was
10.0
mg/
kg/
day
based
on
statistically
significant
decreases
in
RBC,
whole
blood,
plasma
and
brain
cholinesterase;
the
NOAEL
was
1.0
mg/
kg/
day.
Dose
and
Endpoint
for
Risk
Assessment:
NOAEL
=
1.0
mg/
kg/
day
based
on
plasma,
whole
blood,
RBC
and
brain
cholinesterase
inhibition
and
FOB
changes
at
10
mg/
kg/
day.
Comments
about
Proposed
Study/
Endpoint:
The
study
was
selected
because
the
route
of
administration
(oral)
and
the
duration
(90
days)
are
appropriate
for
this
risk
assessment.
It
is
supported
by
the
five
week
dietary
study
in
dogs
(MRID
4202801)
done
to
upgrade
the
chronic
toxicity
study.
The
NOAEL
in
males
was
1.43
mg/
kg/
day
based
on
plasma
cholinesterase
inhibition
at
3.83
mg/
kg/
day.
This
dose
and
endpoint
are
appropriate
for
the
population
of
concern
(infants
and
children).
2.3.3
Dermal
Absorption
Dermal
Absorption
Factor:
A
dermal
absorption
factor
of
12.7%
was
selected
at
the
July
7,
1998
HIARC
meeting;
no
reevaluation
was
conducted
at
the
present
meeting.
13
2.3.4
Short
Term
Dermal
(1
7
days)
Exposure
Study
Selected:
Developmental
Neurotoxicity
Study
§81
8;
OPPTS
870.6300
MRID
No.:
44393701,
45456701,
45456702,
45456703
Executive
Summary:
See
2.1
Acute
Reference
Dose
(RfD)
General
Population
Dose
and
Endpoint
for
Risk
Assessment:
Maternal
NOAEL
of
1
mg/
kg
based
on
alterations
in
FOB
parameters
on
the
first
day
of
dosing
at
10
mg/
kg
Comments
about
Study/
Endpoint:
No
dermal
toxicity
studies
are
available.
The
HIARC
determined
that
study
is
appropriate
for
the
short
term
exposure
time
period
because
effects
(FOB
alterations)
were
observed
after
a
single
dose
and
continued
after
multiple
days
of
dosing.
Since
an
oral
NOAEL
was
used
for
this
endpoint,
a
dermal
absorption
factor
of
12.7%
should
be
used
in
the
risk
assessment.
2.3.5
Intermediate
Term
Dermal
(7
Days
to
Several
Months)
Exposure
Study
Selected:
Subchronic
Neurotoxicity
Study
§
81
8,
OPPTS
870.6200
MRID
Nos.:
44122601
Executive
Summary:
See
2.3.2
Intermediate
Term
Incidental
Oral
Exposure
Dose/
Endpoint
for
Risk
Assessment:
NOAEL
=
1.0
mg/
kg/
day
based
on
plasma,
whole
blood,
RBC
and
brain
cholinesterase
inhibition
and
FOB
changes
at
10
mg/
kg/
day.
Comments
about
Study/
Endpoint:
No
dermal
studies
are
available.
Since
an
oral
NOAEL
was
used
for
this
endpoint,
a
dermal
absorption
factor
of
12.7%
should
be
employed
in
the
risk
assessment.
2.3.6
Long
Term
Dermal
(Longer
than
6
months)
Exposure
Study
Selected:
Chronic
Toxicity
Dog
§
83
1,
OPPTS
870.4100
MRID
Nos.:
40166701,
42022801
Executive
Summary:
See
Chronic
Dietary
section
Dose
and
Endpoint
for
Risk
Assessment:
3.1
mg/
kg/
day
(LOAEL)
based
on
plasma
and
brain
cholinesterase
inhibition
in
females
in
the
1
year
study
Comments
about
Study/
Endpoint:
No
dermal
studies
are
available.
Since
an
oral
NOAEL
was
used
for
this
endpoint,
a
dermal
absorption
factor
of
12.7%
should
be
employed
in
the
risk
14
assessment.
The
reasons
for
selecting
this
oral
study
to
assess
long
term
exposure
are
described
under
2.2
Chronic
Reference
Dose
(RfD).
2.3.7
Inhalation
Exposure
(All
Durations)
There
are
no
studies
available
in
which
carbaryl
was
administered
via
the
inhalation
route,
except
for
the
acute
oral
study
[Toxicity
Category
IV
(LC50
>
3.4
mg/
L)].
2.3.7.1
Short
Term
Inhalation
(1
7
days)
Exposure
Study
Selected:
Developmental
Neurotoxicity
Study
§81
8;
OPPTS
870.6300
MRID
No.:
44393701,
45456701,
45456702,
45456703
Executive
Summary:
See
2.1
Acute
Reference
Dose
(RfD)
General
Population
Dose
and
Endpoint
for
Risk
Assessment:
Maternal
NOAEL
of
1
mg/
kg
based
on
alterations
in
FOB
parameters
on
the
first
day
of
dosing
at
10
mg/
kg
Comments
about
Study/
Endpoint:
No
inhalation
toxicity
studies
are
available.
The
HIARC
determined
that
the
study
is
appropriate
for
the
short
term
exposure
time
period
because
effects
(FOB
alterations)
were
observed
after
a
single
dose
and
continued
after
multiple
days
of
dosing.
Since
an
oral
NOAEL
was
used
for
this
endpoint,
an
inhalation
factor
of
100%
should
be
used
in
the
risk
assessment.
2.3.7.2
Intermediate
Term
Inhalation
(7
Days
to
Several
Months)
Exposure
Study
Selected:
Subchronic
Neurotoxicity
Study
§
81
8,
OPPTS
870.6200
MRID
Nos.:
44122601
Executive
Summary:
See
2.3.2
Intermediate
Term
Incidental
Oral
Exposure
Dose/
Endpoint
for
Risk
Assessment:
NOAEL
=
1.0
mg/
kg/
day
based
on
plasma,
whole
blood,
RBC
and
brain
cholinesterase
inhibition
and
FOB
changes
at
10
mg/
kg/
day.
Comments
about
Study/
Endpoint:
No
inhalation
studies
are
available.
Since
an
oral
NOAEL
was
used
for
this
endpoint,
an
inhalation
absorption
factor
of
100%
should
be
employed
in
the
risk
assessment.
2.3.7.3
Long
Term
Inhalation
(Longer
than
6
months)
Exposure
Study
Selected:
Chronic
Toxicity
Dog
§
83
1,
OPPTS
870.4100
MRID
Nos.:
40166701,
42022801
15
Executive
Summary:
See
Chronic
Dietary
section
Dose
and
Endpoint
for
Risk
Assessment:
LOAEL
of
3.1
mg/
kg/
day
based
on
plasma
and
brain
cholinesterase
inhibition
in
females
in
the
1
year
study.
Comments
about
Study/
Endpoint:
No
inhalation
studies
are
available.
Since
an
oral
NOAEL
was
used
for
this
endpoint,
an
inhalation
absorption
factor
of
100%
should
be
employed
in
the
risk
assessment.
The
reasons
for
selecting
this
oral
study
to
assess
long
term
exposure
are
described
under
2.2
Chronic
Reference
Dose
(RfD).
2.3.5
Margins
of
Exposure
for
Occupational/
Residential
Risk
Assessments
The
HIARC
determined
that
the
acceptable
MOE
for
occupational
exposures
should
be
300
for
the
following
risk
assessments:
long
term
dermal
exposure
and
long
term
inhalation
exposure.
The
additional
3X
is
required
since
a
LOAEL
was
used
in
these
assessments.
The
acceptable
MOEs
for
residential
exposure
will
be
determined
by
the
FQPA
SF
committee.
2.4
Recommendation
for
Aggregate
Exposure
Risk
Assessments
A
common
toxicological
endpoint
of
concern
(alterations
in
FOB
parameters)
was
identified
for
short
term
oral,
dermal
(oral
equivalent)
and
inhalation
(oral
equivalent)
exposure
scenarios.
Therefore,
these
routes
can
be
aggregated
for
the
appropriate
populations.
A
common
toxicological
endpoint
of
concern
(cholinesterase
inhibition)
was
selected
for
intermediate
and
long
term
oral,
dermal
(oral
equivalent)
and
inhalation
(oral
equivalent)
exposure
scenarios.
Therefore,
these
routes
can
be
aggregated
for
these
scenarios
for
the
appropriate
populations.
3
CLASSIFICATION
OF
CARCINOGENIC
POTENTIAL
1.
Combined
Chronic
Toxicity/
Carcinogenicity
Study
in
Rats
MRID
No.:
42918801
Discussion
of
Tumor
Data:.
Male
rats
had
significant
increasing
trends,
and
significant
differences
in
the
pair
wise
comparisons
of
the
7500
ppm
dose
group
with
the
controls,
for
thyroid
follicular
cell
adenomas
and
combined
adenomas
and/
or
carcinomas,
and
urinary
bladder
transitional
cell
papillomas,
carcinomas,
and
combined
papillomas
and/
or
carcinomas,
all
at
p
<
0.01.
Female
rats
had
significant
increasing
trends
in
urinary
bladder
transitional
cell
papillomas,
carcinomas,
and
combined
papillomas
and/
or
carcinomas,
all
at
p
<
0.01.
There
were
significant
differences
in
the
pair
wise
comparisons
of
the
7500
ppm
dose
group
with
the
controls
for
urinary
bladder
transitional
cell
papillomas
(p
<
0.05),
carcinomas
(p
<
0.05),
and
16
combined
carcinomas
and/
or
papillomas
(p
<
0.01).
Adequacy
of
the
Dose
Levels
Tested:
At
meetings
on
October
27
and
December
8,
1993,
the
HED
Cancer
Peer
Review
Committee
determined
that
the
7500
ppm
dose
was
excessive
based
on
the
following
findings:
1)
changes
in
body
weight
gain
during
week
13
for
males
and
females
by
40%
and
52%,
respectively,
as
compared
to
controls;
2)
decreased
food
efficiency;
3)
alterations
in
hematology
and
clinical
chemistry;
and
4)
decreases
in
plasma,
RBC
and
brain
cholinesterase
at
weeks
53
and
105.
The
CPRC
also
concluded
that
the
mid
dose
(1500
ppm)
was
not
adequate
for
carcinogenicity
testing.
The
November
7,
2001
CARC
meeting
affirmed
that
the
high
dose
was
excessive
and
the
mid
dose
was
not
sufficiently
high
enough
to
test
the
carcinogenic
potential
of
carbaryl
in
rats.
2.
Carcinogenicity
Study
in
Mice
MRID
No.:
42786901
Discussion
of
Tumor
Data:
Male
mice
had
significant
increasing
trends
in
kidney
tubule
cell
adenomas
(p
<
0.05),
carcinomas
(p
<
0.05)
and
combined
adenomas
and/
or
carcinomas
(p
<
0.01).
There
was
also
a
significant
difference
in
the
pair
wise
comparison
of
the
8000
ppm
dose
group
with
the
controls
for
combined
kidney
tubule
cell
adenomas
and/
or
carcinomas
at
p
<
0.05.
There
were
significant
differences
in
the
pair
wise
comparisons
of
all
dose
groups
(100,
1000
and
8000
ppm)
with
the
controls
for
hemangiosarcomas,
all
at
p
<
0.05.
There
were
significant
differences
in
the
pair
wise
comparisons
of
1000
and
8000
ppm
dose
groups
with
the
controls
for
hemangiomas
and/
or
hemangiosarcomas
combined,
both
at
p
<
0.05.
Female
mice
had
significant
increasing
trends
in
hepatocellular
adenomas
and
adenomas,
carcinomas
and/
or
hepatoblastomas
combined,
both
at
p
<
0.01.
There
were
significant
differences
in
the
pair
wise
comparisons
of
the
8000
ppm
dose
group
with
the
controls
for
hepatocellular
adenomas
at
p
<
0.05
and
for
hepatocellular
adenomas,
carcinomas
and/
or
hepatoblastomas
combined
at
p
<
0.01.
There
was
a
significant
increasing
trend
at
p
<
0.01,
and
a
significant
difference
in
the
pair
wise
comparison
of
the
8000
ppm
dose
group
with
the
controls
at
p
<
0.05,
for
hemangiosarcomas.
There
was
also
a
significant
increasing
trend
for
hemangiomas
and/
or
hemangiosarcomas
combined
at
p
<
0.05.
Adequacy
of
the
Dose
Levels
Tested:
At
meetings
on
October
27
and
December
8,
1993,
the
HED
Cancer
Peer
Review
Committee
concluded
that
the
8000
ppm
dose
was
excessive
based
on
the
significantly
decreased
body
weight
gain
in
males
(33%)
and
females
(19%)
during
week
13,
a
significant
decrease
in
RBC
and
brain
cholinesterase
activity,
clinical
signs
of
toxicity
and
histopathological
changes
in
the
bladder,
kidneys
and
spleen
in
both
sexes.
The
November
7,
2001
CARC
meeting
affirmed
that
the
high
dose
was
excessive.
3.
Carcinogenicity
and
Other
Studies
in
p53
Knockout
Mice
In
a
special,
non
guideline
study
(MRID
45281801),
heterozygous
p53
deficient
(knockout)
male
mice
(20/
group)
were
administered
carbaryl
in
the
diet
at
concentrations
of
0,
10,
30,
17
100,
300,
1000
and
4000
ppm
(approximately
0,
1.8,
5.2,
17.5,
51.2,
164.5
and
716.6
mg/
kg/
day,
respectively)
for
six
months.
The
doses
selected
for
this
study
were
based
on
two
28
day
studies
(MRID
45236603)
in
wild
type
mice
in
which
body
weight
decreases
were
observed
at
4000
and
8000
ppm
concentrations
of
carbaryl
in
the
diet.
A
validation
study
(MRID
45281802)
demonstrated
that
vascular
tumors
occur
in
heterozygous
p53
deficient
mice
within
6
months
of
administration
of
a
known
genotoxic
carcinogen
(urethane).
These
studies
were
conducted
to
demonstrate
that
carbaryl
is
a
non
genotoxic
carcinogen.
In
the
standard
mouse
carcinogenicity
study
(MRID
42786901)
at
dietary
concentrations
of
0,
100,
1000
or
8000
ppm,
there
was
an
increased
incidence
of
vascular
neoplasms
(hemangiomas
and
hemangiosarcomas)
in
all
treated
males
and
in
the
8000
ppm
group
females.
There
was
an
increased
incidence
of
adenomas,
multiple
adenomas
and
carcinomas
of
the
kidney
in
the
8000
ppm
group
males.
The
incidence
of
hepatic
neoplasms
(adenomas,
carcinomas
and
one
hepatoblastoma)
was
increased
in
the
8000
ppm
group
females.
At
meetings
on
October
27
and
December
8,
1993,
the
HED
Cancer
Peer
Review
Committee
concluded
that
the
8000
ppm
dose
was
excessive.
Therefore,
the
relevance
of
tumors
at
this
dose
was
questionable.
In
the
p53
knockout
mouse
study
with
carbaryl,
there
was
a
slight
decrease
in
body
weight
and
food
consumption
in
the
4000
ppm
group.
No
other
treatment
related
effects
were
observed,
except
globular
deposits
in
the
urinary
bladder
were
observed
in
a
high
proportion
of
the
mice
treated
at
100
ppm
of
carbaryl
and
above
with
a
dose
related
increase
in
incidence
and
severity.
There
was
no
evidence
of
local
irritation
or
hypertrophy
of
the
bladder
epithelium.
There
was
no
evidence
of
neoplastic
or
preneoplastic
changes
in
the
vascular
tissue
of
any
organs
examined.
The
study
is
classified
Acceptable
(non
guideline).
This
is
a
special
study
not
submitted
to
fulfill
a
data
requirement.
4.
Classification
of
Carcinogenic
Potential.
The
carcinogenic
potential
of
carbaryl
was
evaluated
by
the
HED
Carcinogenicity
Peer
Review
Committee
on
October
27
and
December
8,
1993
(May
12,
1994
report).
The
Committee
concluded
that
carbaryl
induced
tumors
at
multiple
sites
in
the
rat
and
mouse
at
doses
considered
to
be
excessively
toxic.
Only
hemangiosarcomas
in
the
CD
1
male
mouse
occurred
at
a
dose
which
was
considered
adequate
and
not
excessive.
The
Committee
concluded
that
carbaryl
should
be
classified
as
a
Group
C
possible
human
carcinogen.
Both
the
low
dose
extrapolation
(Q1*)
approach
and
a
margin
of
exposure
(MOE)
approach
were
suggested
as
methods
of
quantifying
the
cancer
risk
in
humans.
In
addition,
a
RfD
approach
was
suggested
to
provide
the
most
sensitive
non
cancer
health
endpoint
for
comparison
to
the
linear
and
MOE
approaches.
The
Committee
requested
additional
metabolism
studies
and
genotoxicity
studies
to:
1)
direct
the
selection
of
the
more
appropriate
quantitative
approach;
and
2)
provide
insight
into
the
significance
of
tumors
seen
only
at
excessively
toxic
doses.
Additional
metabolism
studies
were
submitted
and
evaluated
by
a
subgroup
of
the
HED
Cancer
Assessment
Review
Committee
(CARC)
in
a
memorandum
signed
October
5,
1998.
The
subgroup
concluded
that
the
available
metabolism
studies
were
not
adequate
to
support
a
nonlinear
mode
of
action
and
recommended
that
the
default
linear
approach
be
used
for
risk
18
quantitation.
In
1996,
the
registrant
convened
a
Pathology
Working
Group
(PWG)
which
reevaluated
all
histopathology
findings
of
both
the
two
year
rat
and
mouse
studies.
The
results
of
this
PWG
are
discussed
below
with
the
study
summaries.
At
a
November
7,
2001
meeting,
the
HED
CARC
classified
carbaryl
as
"Likely
to
be
carcinogenic
to
humans"
based
on
a
statistically
significant
increase
in
hemangiosarcomas
in
male
mice
at
all
doses
tested
(100,
1000
and
8000
ppm),
all
at
p<
0.05.
In
addition,
there
were
preneoplastic
lesions
in
the
bladders
of
male
rats
at
the
mid
dose
(1500
ppm)
which
was
not
considered
adequate
for
carcinogenicity
testing.
Bladder
tumors
were
observed
in
male
rats
at
the
high
dose
which
was
considered
excessive.
The
unit
risk,
Q1
*
(mg/
kg/
day)
1
,
of
Carbaryl
is
8.75
x
10
4
in
human
equivalents
based
on
the
1996
PWG
re
read
of
the
male
mouse
hemangiosarcoma
tumor
rates.
4
MUTAGENICITY
During
the
meetings
on
October
27,
and
December
8,
1993,
the
CPRC
(1994)
recommended
that
an
in
vivo
cytogenetic
assay
in
rodents
be
conducted
to
provide
insight
into
the
structural
and/
or
numerical
aberrations,
which
were
observed
in
the
gene
mutation
assay
and
reported
in
the
open
literature.
In
response
to
CPRC's
request,
a
mouse
micronucleus
assay
(MRID
44069301)
was
submitted
to
fulfill
the
guideline
requirement
but
it
was
classified
as
unacceptable.
A
recent
review
of
the
data
from
the
submitted
studies
and
the
published
literature
were
in
general
agreement
and
show
that
carbaryl
is
clastogenic
in
vitro.
The
wide
variety
of
induced
aberrations
(both
simple
and
complex)
was
consistent
between
the
submitted
study
and
the
open
literature.
However,
there
are
inconsistencies
relative
to
the
requirement
for
S9
activation.
Nevertheless,
the
two
in
vivo
studies
for
micronuclei
induction
or
chromosome
aberrations
were
negative.
Similarly,
the
6
month
p53
knockout
transgenic
mouse
bioassay
was
negative
up
to
a
high
level
(4000
ppm,
.
720
mg/
kg/
day)
that
approached
the
limit
dose
for
a
mouse
carcinogenicity
assay.
Carbaryl
was
also
negative
for
DNA
binding
in
the
livers
of
mice
treated
with
8000
ppm
for
2
weeks
but
the
study
was
considered
to
be
of
limited
sensitivity
by
the
CARC
Metabolism
Subgroup
(HED
Document
No.
012892).
The
same
Subgroup
identified
epoxide
intermediates
of
carbaryl
which
were
found
to
be
conjugated
to
glucuronide,
"rapidly
metabolized
and
excreted
as
any
endogenous
epoxide
would
be".
Overall,
these
findings
indicate
that
carbaryl
produces
epoxides
and
its
DNA
reactivity
is
manifested
as
chromosomal
aberrations
in
cultured
mammalian
cells.
Other
in
vitro
studies
indicate
carbaryl's
effects
on
karyokinesis
and
cytokinesis,
as
well
as
stress
genes
associated
with
oxidative
damage.
Based
on
these
considerations,
it
was
concluded
that
there
is
a
concern
for
mutagenicity,
which
is
somewhat
lessened
because
of
the
lack
of
an
effect
in
in
vivo
mutagenicity
studies.
19
GENE
MUTATIONS
Mutagenicity
Salmonella
typhimurium/
Mammalian
Microsome
Mutagenicity
Assay
(Ames
test)
In
a
Salmonella/
mammalian
activation
gene
mutation
assay
(MRID
41370303),
carbaryl
technical
(99.3%)
was
initially
evaluated
in
the
Salmonella
typhimurium/
microsome
mutagenicity
assay
over
a
concentration
range
of
5
to
1000
µg/
plate.
The
test
material
was
not
mutagenic,
however
the
highest
assayed
dose
was
cytotoxic
in
S.
typhimurium
strains
TA98
and
TA100,
but
not
in
strains
TA1535,
TA1537,
or
TA1538.
Accordingly,
the
assay
was
repeated
with
six
concentrations
(10
to
2000
µg/
plate
+/
S9).
Results
from
the
repeat
assay
indicated
that
2000
µg/
plate
+/
S9
was
cytotoxic
in
strains
TA98
and
TA100,
and
the
remaining
doses
were
not
mutagenic.
It
is
concluded,
therefore,
that
carbaryl
technical
was
assayed
to
an
appropriately
high
concentration
with
no
evidence
of
mutagenicity
in
a
wellconducted
study.
The
study
is
classified
as
acceptable/
guideline
and
satisfies
the
guideline
requirements
(§
84
2)
of
bacterial
reverse
mutation
test.
Mutagenicity
Mammalian
Cells
in
Culture
Gene
Mutation
Assay
in
Chinese
Hamster
Ovary
(CHO)
Cells
In
a
mammalian
cells
in
culture
gene
mutation
assay
in
Chinese
Hamster
Ovary
(CHO)
Cells
(MRIDs
41370302,
41420201),
carbaryl
technical
(99.3%)
was
evaluated
in
two
nonactivated
and
three
S
9
activated
Chinese
hamster
ovary
(CHO)
cell
forward
mutation
assays.
The
findings
from
both
nonactivated
assays
were
in
good
agreement
and
indicated
that
over
a
concentration
range
of
1
to
300
µg/
mL,
the
test
material
did
not
induce
a
mutagenic
response.
Doses
$
200
µg/
mL
were
severely
cytotoxic
(<
10%
cell
survival),
and
<50%
of
the
cells
survived
exposure
to
$
50
µg/
mL.
Carbaryl
was
less
cytotoxic
in
the
presence
of
S9
activation
as
indicated
by
increased
survival
at
comparable
levels
in
the
preliminary
cytotoxicity
test
(e.
g.,
29.5%
survival
at
62.5
µg/
mL
S9
as
compared
with
95.7%
survival
at
62.5
µg/
mL
+S9)
and
the
initial
mutation
assay
(e.
g.,
18.1%
survival
at
100
µg/
mL
S9
as
compared
with
46.8%
at
100
µg/
mL
+S9).
There
was
no
definitive
evidence
of
increased
mutation
frequencies
(MFs)
in
this
trial.
The
second
S9
activated
trial
was
aborted
because
of
excessive
cytotoxicity
at
test
material
levels
of
$
10
µg/
mL.
Results
from
the
third
S9
activated
trial
(dose
range:
1
to
80
µg/
mL)
showed
severe
cytotoxic
effects
at
levels
$
60
µg/
mL;
no
evidence
of
mutagenic
effect
was
seen
at
the
remaining
doses.
The
results
of
the
assays
provide
no
clear
indication
of
a
mutagenic
response,
however,
the
study
does
not
fully
support
a
negative
conclusion.
The
conflicting
cytotoxicity
data
for
the
S9
activated
assays
provide
no
assurance
that
the
final
S9
activated
mutation
assay
was
conducted
over
an
appropriate
dose
range.
The
study
is
classified
as
unacceptable/
guideline
and
does
not
satisfy
the
guideline
requirements
(§
84
2)
for
an
in
vitro
mammalian
cell
gene
mutation
test.
20
CHROMOSOME
ABERRATIONS
Mutagenicity
Mammalian
Cells
in
Culture
Cytogenetic
Assay
Carbaryl
(technical)
was
assayed
for
clastogenic
effects
in
both
the
presence
and
absence
of
S9
activation
using
Chinese
hamster
ovary
(CHO)
cells
(MRID
41370301).
Because
of
severe
cell
cycle
delay,
which
was
more
pronounced
without
S9
activation,
a
20
hour
cell
harvest
was
selected
to
evaluate
seven
nonactivated
doses
ranging
from
5
to
100
:
g/
mL.
In
the
presence
of
S9
activation,
cells
exposed
to
carbaryl
at
doses
of
25,
50,
75,
100,
150,
200,
250,
and
300
:
g/
mL
were
harvested
30
hours
post
treatment.
Results
indicated
that
the
nonactivated
test
material
was
more
cytotoxic
than
the
S9
activated
test
material
(i.
e.,
few
metaphases
were
recovered
at
75
and
100
:
g/
mL
,
and
moderate
to
slight
cytotoxic
effects
were
seen
at
doses
$
10.0
:
g/
mL).
With
the
exception
of
a
single
rare
complex
aberration
(quadriradial)
scored
at
the
50.0
:
g/
mL
dose
level,
there
was
no
evidence
of
a
clastogenic
effect.
By
contrast,
in
the
S9
activated
assays,
all
scored
doses
(150,
200,
250,
and
300
:
g/
mL)
at
both
harvest
times
induced
significant
(p
0.01)
increases
in
the
percentage
of
cells
with
aberrations.
The
majority
of
S9
activated
doses
(both
harvests)
also
induced
significant
(p
0.01)
increases
in
the
percentage
of
cells
with
>1
aberration.
At
both
the
20
and
30
hour
harvest
times,
cytotoxicity
(i.
e.,
reduced
monolayers,
dead
cells,
and/
or
reduced
mitotic
cells)
were
observed
at
levels
$
200
:
g/
mL.
Induced
structural
damage
included
simple
(i.
e.,
chromatid
and
chromosome
breaks)
and
complex
aberrations
(i.
e.,
triadials,
quadriradials,
complex
rearrangements,
dicentrics
and
rings).
The
data
show
little
or
no
dose
responsiveness
and
the
lowest
reactive
level
of
carbaryl
was
not
determined.
It
was
concluded,
however,
that
the
study
was
technically
sound
and,
therefore,
acceptable/
guideline.
The
study
satisfies
the
Guideline
requirements
(§
84
2)
for
an
in
vitro
mammalian
cell
chromosomal
aberration
test.
Mutagenicity
Mouse
Micronucleus
Test
In
a
mouse
micronucleus
assay
(MRID
No:
44069301),
groups
of
five
male
and
five
female
CD
1
mice
received
single
oral
gavage
administrations
of
50,
100
or
200
mg/
kg
carbaryl
(99.9%)
once
daily
for
2
days.
Based
on
analytical
determinations,
average
daily
doses
were
.
34,
79
or
180
mg/
kg.
Mice
were
sacrificed
at
24
and
48
hours
postadministration
of
the
second
dose
and
harvested
bone
marrow
cells
were
examined
for
the
incidence
of
micronucleated
polychromatic
erythrocytes
(MPEs).
The
test
material
was
delivered
as
suspensions
prepared
in
0.5%
carboxymethyl
cellulose.
The
minimal
toxicity
(i.
e.,
lethargy
which
lasted
for
2
hours)
in
the
absence
of
cytotoxicity
to
the
target
cells
does
not
support
the
testing
of
the
maximum
tolerated
dose
(MTD).
The
positive
control
induced
the
expected
high
yield
of
MPEs
in
males
and
females.
Carbaryl
did
not
induce
a
clastogenic
or
aneugenic
effect
in
either
sex
at
any
dose
or
sacrifice
time.
However,
there
was
no
convincing
evidence
that
the
MTD
was
achieved.
The
study
is
classified
as
unacceptable/
guideline
and
does
not
satisfy
the
guideline
requirements(§
84
2;
OPPTS
870.5385)
for
in
vivo
cytogenetic
mutagenicity
data.
2
Onfelt,
A.,
Klasterska,
I.
(1984).
Sister
chromatid
exchanges
and
thioguanine
resistance
in
V79
Chinese
hamster
cells
after
treatment
with
the
aneuploidy
inducing
agent
carbaryl
+/
S9
mix.
Mutat
Res
125(
2):
269
274
3
Ahmed,
F.
E.,
Lewis,
N.
J.,
Hart,
R.
W.
(1977).
Pesticide
induced
ouabain
resistant
mutants
in
Chinese
hamsterV79
cells.
Chem
Biol
Interact,
19:
369
374.
4
Onfelt,
A.,
Klasterska,
I.
(1983).
Spindle
disturbances
in
mammalian
cells
II.
Induction
of
viable
aneuploidy/
polyploidy
cells
and
multiple
chromatid
exchanges
after
treatment
of
V79
Chinese
hamster
cells
with
carbaryl,
modifying
effect
of
glutathione
and
S9.
Mutat
Res
119:
319
330.
5
Delescluse,
C.
et
al
(2001).
Induction
of
cytochrome
P450
1A1
gene
expression,
oxidative
stress,
and
genotoxicity
by
carbaryl
and
thiabendazole
in
transfected
human
HepG2
and
lymphoblastoid
cells.
Biochem
Pharmacol.
61(
4):
399
407.
6
Renglin,
A.,
Olsson
A.,
Wachtmeister,
C.,
Onfelt,
A.
(1998).
Mitotic
disturbance
by
carbaryl
and
the
metabolite
1
naphthol
may
induce
kinase
mediated
phosphorylation
of
1
naphthol
to
the
protein
21
OTHER
MUTAGENIC
EFFECTS
Mutagenicity
UDS
Assay
In
a
UDS
Assay
in
primary
rat
hepatocytes
(MRID
41370301),
under
the
conditions
of
two
independent
trials,
six
doses
of
carbaryl
technical
(99.3%)
ranging
from
0.5
to
25.0
µg/
mL
in
the
first
assay
and
six
doses
ranging
from
5.0
to
25.0
µg/
mL
in
the
repeat
assay
did
not
induce
an
appreciable
increase
in
the
net
nuclear
grain
counts
of
treated
rat
hepatocytes.
Doses
>25.0
µg/
mL
were
severely
cytotoxic;
reduced
cell
survival
(
25%)
was
observed
at
25.0
µg/
mL
in
both
assays.
Although
an
increase
in
the
percentage
of
cells
with
$
6
grains
per
nucleus
was
seen
in
the
initial
test,
the
increase
was
confined
to
a
single
dose
(10
µg/
mL)
and
was
not
dose
related
or
reproducible.
The
study
demonstrated
that
carbaryl
is
not
genotoxic
in
this
test
system
at
doses
of
5.0
to
25.0
µg/
mL.
The
study
is
classified
as
acceptable/
guideline
and
satisfies
the
guideline
requirements
(§
84
2)
for
a
unscheduled
DNA
synthesis
in
mammalian
cells
in
culture.
STUDIES
FROM
THE
OPEN
LITERATURE
Studies
in
the
open
literature
indicate
that
Carbaryl
is
not
mutagenic
in
bacteria
but
produced
conflicting
results
in
Chinese
hamster
V79
gene
mutation
assays
[negative
in
the
study
of
Onfelt
and
Klasterska
2
but
weakly
positive
minus
S9
metabolic
activation
as
reported
by
Ahmed
et
al.
3
Nonactivated
carbaryl
induced
aneuploidy
and
sister
chromatid
exchanges
in
V79
cells;
the
addition
of
S9
or
an
excess
of
glutathione
eliminated
these
responses
(Onfelt
and
Klasterska
4,2
).
In
the
former
study,
multiple
chromatid
exchanges
(quadriradials
and
complex
rearrangements)
plus
chromosome
breaks
were
also
induced
by
100
mM
carbaryl;
this
effect
was
largely
abolished
by
the
simultaneous
addition
of
S9
or
glutathione.
There
are
positive
data
for
DNA
damage
in
a
human
lymphoblastoid
cell
line
(induction
of
CYP1A1
genes);
carbaryl
also
activated
other
stress
genes
known
to
be
sensitive
to
oxidative
damage
(Delescluse
et
al.
5
).
Also,
carbaryl
causes
depolymerization
of
spindle
microtubules
and
an
apparent
uncoupling
of
karyokinesis
and
cytokinesis
in
cultured
V79
cells
(Renglin
et
al,
6,7
).
phosphatase
inhibitor
1
naphthyl
phosphate.
Mutagenesis
13:
345
352.
7
Renglin,
A.,
Harmala
Brasken,
A.,
Eriksson,
J.,
Onfelt,
A.
(1999).
Mitotic
aberrations
by
carbaryl
reflect
tyrosine
kinase
inhibition
with
coincident
up
regulation
of
serine/
threonine
protein
phosphatase
activity:
implications
for
coordination
of
karyokinesis
and
cytokinesis.
Mutagenesis
14:
327
333.
8
Usha
Rani,
M.
V.,
Reddi,
O.
S.
and
Reddy,
P.
P.
(1980).
Mutagenicity
Studies
Involving
Aldrin,
Endosulfan,
Dimethoate,
Phosphamidon,
Carbaryl
and
Ceresan.
Bull
Environm.
Contam.
Toxicol
25:
277
282.
9
Dzwonkowska,
A.,
Hubner,
H.
(1986).
Induction
of
chromosomal
aberrations
in
the
Syrian
hamster
by
insecticides
tested
in
vivo.
Arch
Toxicol
58(
3):
152
156.
22
In
contrast
to
the
in
vitro
data,
carbaryl
administered
by
oral
gavage
at
1/
3
of
the
LD50
(146
mk/
kg/
day)
for
2
consecutive
days
was
negative
for
micronuclei
induction
in
Swiss
albino
male
mice
(Usha
Rani
et
al.
8
).
Carbaryl
was
also
negative
for
the
induction
of
chromosome
aberrations
in
bone
marrow
cells
of
Syrian
hamsters
treated
with
1/
10,
1/
5
and
½
of
the
LD50
and
the
LD50
(Dzwonkowska
and
Hubner
9
).
5
FQPA
CONSIDERATIONS
5.1
Adequacy
of
the
Data
Base
The
data
base
is
adequate
for
FQPA
considerations.
The
following
acceptable
studies
are
available:
Acute
delayed
neurotoxicity
study
in
hen
Acute
and
subchronic
neurotoxicity
studies
in
rats
Developmental
toxicity
studies
in
rats
and
rabbits
Multi
generation
reproduction
study
in
rats
Developmental
neurotoxicity
study
in
rats
5.2
Neurotoxicity
Carbaryl
was
not
a
delayed
neurotoxicant
in
the
hen.
In
the
acute
neurotoxicity
study
with
gavage
administration,
FOB
changes
(increased
tremors
and
ataxia,
decreased
body
temperature
and
arousal)
and
decreased
motor
activity
were
observed
in
males
and
females
at
50
and
125
mg/
kg.
Decreases
in
plasma
(males
only),
whole
blood,
RBC
and
brain
cholinesterase
were
seen
at
10,
50
and
125
mg/
kg/
day.
In
the
subchronic
neurotoxicity
study
with
gavage
administration,
there
was
an
increased
incidence
of
tremors
and
salivation
in
males
and
females
at
30
mg/
kg/
day.
FOB
changes
(increases
in
tremors,
gait
alteration,
pinpoint
pupils,
salivation,
etc.)
were
observed
in
males
and
females
at
10
and
30
mg/
kg/
day.
Motor
activity
was
decreased
in
males
and
females
at
30
mg/
kg/
day.
Plasma,
RBC,
whole
blood
and
brain
ChE
were
decreased
in
males
and
females
at
10
and
30
mg/
kg/
day.
At
necropsy,
there
was
an
increase
in
dark
areas
of
the
meninges
of
the
30
mg/
kg/
day
males.
23
In
the
developmental
neurotoxicity
study
with
gavage
administration,
changes
in
FOB
parameters
(increases
in
pinpoint
pupils,
tremors,
ataxia,
overall
gait
incapacity)
were
seen
in
the
maternal
animals
at
10
mg/
kg/
day.
RBC
and
whole
blood
ChE
was
decreased
on
gestation
day
(GD)
20
and
lactation
day
(LD)
10
at
10
mg/
kg/
day.
Plasma
ChE
was
decreased
on
GD
20,
LD4
and
LD10
at
10
mg/
kg/
day.
Brain
ChE
was
decreased
at
10
mg/
kg/
day.
In
both
the
F1
pups
and
adults,
there
were
differences
in
the
morphometric
measurements
from
the
control
group
at
10
mg/
kg/
day.
In
the
chronic
dog
study
with
dietary
administration,
clinical
signs
of
neurotoxicity
(emesis,
lacrimation,
salivation
and
tremors)
were
observed
in
females
at
1250
ppm
(31.3
mg/
kg/
day).
Plasma
and
brain
ChE
were
decreased
in
females
at
doses
of
125
ppm
(3.1
mg/
kg/
day)
and
above
and
in
males
at
400
ppm
(10
mg/
kg/
day)
and
above.
RBC
ChE
was
decreased
in
males
and
females
at
400
ppm
and
above.
In
a
five
week
study
done
to
upgrade
the
chronic
study,
plasma
ChE
was
decreased
in
males
at
125
ppm
(3.83
mg/
kg/
day),
the
highest
dose
tested.
In
the
mouse
carcinogenicity
study
with
dietary
administration,
there
were
clinical
signs
of
toxicity
(hunched
posture,
thin
and
languid
appearance,
squinted
and
opaque
eyes,
etc.)
at
8000
ppm
(M:
1248.93
mg/
kg/
day;
F:
1440.62
mg/
kg/
day)
but
they
were
not
the
usual
signs
seen
with
cholinesterase
inhibiting
chemicals.
RBC
cholinesterase
(ChE)
was
statistically
significantly
decreased
in
the
1000
ppm
(145.99
mg/
kg/
day)
(23%
9
)
and
8000
ppm
(30%
9
)
group
males
at
week
53.
RBC
ChE
was
decreased
in
the
8000
ppm
group
females
(24%
9
)
at
week
105,
although
the
change
was
not
statistically
significant.
Brain
ChE
was
statistically
significantly
decreased
in
the
1000
and
8000
ppm
group
males
at
both
weeks
53
and
105
(13
18%
9
for
the
1000
ppm
group;
40
57%
9
for
the
8000
ppm
group)
and
in
the
8000
ppm
females
(34
47%
9
).
Brain
ChE
was
also
significantly
decreased
(13%
9
)
in
the
1000
ppm
(180.86
mg/
kg/
day)
group
females
at
week
53.
However,
the
percentage
decreases
from
the
control
level
were
less
than
20%
for
the
1000
ppm
group
males
and
females
at
both
weeks
53
and
105.
Therefore,
the
biological
significance
of
these
findings
is
questionable.
Plasma
ChE
values
were
not
affected
by
treatment.
In
the
rat
combined
chronic
toxicity/
carcinogenicity
study
with
dietary
administration,
there
were
increased
signs
of
toxicity
in
the
7500
ppm
(M:
349.5
mg/
kg/
day;
F:
484.6
mg/
kg/
day)
group,
but
they
were
not
the
usual
signs
seen
with
cholinesterase
inhibiting
chemicals.
Plasma
cholinesterase
was
decreased
in
the
7500
ppm
males
(27
42%)
and
females
(46
57%)
at
all
of
the
testing
intervals
(weeks
27,
53,
79
and
105),
however
all
of
the
changes
were
not
statistically
significant.
RBC
cholinesterase
was
decreased
in
the
7500
males
(19
37%)
and
females
(25
38%)
and
in
the
1500
ppm
(60.2
mg/
kg/
day)
males
(10
23%)
and
females
(12
26%)
at
most
of
the
testing
intervals.
At
weeks
53
and
105,
brain
cholinesterase
was
statistically
significantly
decreased
in
the
7500
ppm
males
(8
28%)
and
females
(22
31%).
In
the
recovery
group,
cholinesterase
values
had
returned
to
normal
levels
by
week
56.
24
5.3
Developmental
Toxicity
Prenatal
developmental
toxicity
study
in
the
rat
In
a
developmental
toxicity
study
(MRID
44732901),
carbaryl
(99%
a.
i.)
in
an
aqueous
methylcellulose
suspension
was
administered
by
gavage
at
0,
1,
4,
and
30
mg/
kg/
day
to
pregnant
Crl:
CD
(SD)
BR
rats
(25/
dose)
during
gestation
days
(GDs)
6
through
20.
At
GD
21,
surviving
dams
were
sacrificed
and
necropsied.
There
were
no
treatment
related
gross
pathologic
findings
noted
in
any
of
the
dams.
There
were
no
differences
of
toxicological
concern
in
mortality,
pregnancy
rate,
numbers
of
corpora
lutea,
implantations,
viable
fetuses,
pre
and
post
implantation
losses,
placental
weights,
and
sex
ratio.
At
30
mg/
kg/
day,
at
least
one
occurrence
of
post
dosing
salivation
occurred
in
18/
25
of
the
dams
(vs
0/
25
controls).
This
clinical
sign
appeared
within
20
minutes
of
treatment,
disappeared
after
approximately
one
hour,
and
was
observed
from
GD
13
to
20.
There
were
no
deaths
and
no
other
treatment
related
clinical
signs.
Body
weights
of
the
high
dose
dams
were
3
8%
less
than
controls
throughout
the
study
(not
statistically
significant);
their
corrected
(for
gravid
uterine
weight)
body
weights
and
body
weight
gains
were
decreased
(p
0.01)
by
7
and
38%,
respectively.
Body
weight
gains
in
this
group
were
decreased
immediately
after
initiation
of
dosing
(GDs
6
9,
9
108%,
p
0.01)
and
throughout
treatment
(overall,
9
27%,
p
0.01).
Food
consumption
(g/
animal/
day)
was
decreased
throughout
the
treatment
period
(
10
17%,
p
0.01).
There
were
no
differences
of
toxicological
concern
observed
in
the
mid
and
low
dose
groups.
The
maternal
LOAEL
is
30
mg/
kg/
day
based
on
clinical
signs
of
toxicity,
decreased
body
weight
gains
and
food
consumption.
The
maternal
NOAEL
is
4
mg/
kg/
day.
In
the
high
dose
fetuses,
mean
fetal
body
weights
were
reduced
(
7
8%,
p
0.01).
Additionally,
the
following
were
observed
in
the
high
dose
male
and
female
fetuses:
(i)
an
increase
in
incomplete
ossification
of
the
5th
sternebra,
(ii)
unossified
7th
cervical
centrum,
(iii)
incomplete
ossification
of
7th
cervical
centrum,
and
(iv)
unossified
1st
metatarsal.
No
effects
on
fetal
viability
were
observed.
There
were
no
treatment
related
effects
in
developmental
parameters
observed
in
the
mid
and
low
dose
groups.
The
developmental
LOAEL
is
30
mg/
kg/
day
based
on
decreased
fetal
body
weights
and
increased
incomplete
ossification
of
multiple
bones.
The
developmental
NOAEL
is
4
mg/
kg/
day.
The
developmental
toxicity
study
in
the
rat
is
classified
as
acceptable
(§
83
3(
a))
and
does
satisfy
the
guideline
requirement
for
a
developmental
toxicity
study
in
the
rat.
25
Prenatal
developmental
toxicity
study
in
the
rabbit
In
a
developmental
toxicity
study
(MRID
44904202),
carbaryl
(99%
a.
i.)
in
an
aqueous
methylcellulose
suspension
was
administered
by
gavage
at
doses
of
0,
5,
50
or
150
mg/
kg/
day
to
pregnant
New
Zealand
White
rabbits
(22/
dose)
during
Gestation
Days
(GD)
6
29.
On
GD
25,
blood
was
collected
1
hour
post
dosing
for
plasma
and
red
blood
cell
(RBC)
cholinesterase
(ChE)
measurements.
At
GD
30,
surviving
dams
were
sacrificed
and
necropsied;
fetuses
were
examined
for
evidence
of
developmental
effects.
Maternal
toxicity
at
150
mg/
kg/
day
was
observed
as
statistically
significant
decreased
body
weight
gain
as
compared
to
the
control
value
during
GD
6
9
(208%),
GD
6
29
(dosing
period,
53%),
GD
3
30
(33%)
and
gestation
(GD
0
GD
30,
38%).
Corrected
body
weight
change
was
also
decreased
at
this
dose
(
219.73
g
vs
81.86
g
in
the
control).
Although
not
statistically
significant,
the
body
weight
decreases
at
50
mg/
kg/
day
can
be
considered
biologically
significant
for
GD
6
9
(55%),
GD
6
29
(25%),
GD
3
30
(14%)
and
gestation
(14%).
There
was
no
treatment
related
effect
on
food
consumption.
Statistically
significantly
decreases
in
plasma
(46
68%)
and
RBC
(19
27%)
ChE
were
seen
at
50
and
150
mg/
kg/
day.
Maternal
LOAEL
=
50
mg/
kg/
day
based
on
decreased
body
weight
gain
and
decreased
plasma
and
RBC
ChE;
Maternal
NOAEL
=
5
mg/
kg/
day
The
only
evidence
of
developmental
toxicity
was
a
statistically
significant
decrease
in
fetal
body
weights
of
10%
(when
calculated
for
all
fetuses
or
individually
for
males
and
females)
at
150
mg/
kg/
day.
There
were
no
treatment
related
developmental
effects
observed
in
the
mid
and
low
dose
groups.
Developmental
Toxicity
LOAEL
is
150
mg/
kg/
day
based
on
decreased
fetal
weight.
Developmental
Toxicity
NOAEL
is
50
mg/
kg/
day
The
developmental
toxicity
study
in
the
rabbit
is
classified
as
acceptable/
guideline
and
does
satisfy
the
guideline
requirement
for
a
developmental
toxicity
study
in
the
rabbit.
5.4
Reproductive
Toxicity
In
a
two
generation
reproduction
study
(MRID
45448101),
carbaryl
(99.1%
a.
i,
Lot
No.
E1208008)
was
given
in
the
diet
to
groups
of
30
male
and
30
female
F0
and
F1
rats
(CD
®
[SD]
IGS
BR
(Sprague
Dawley))
at
concentrations
of
0,
75,
300,
or
1500
ppm.
The
dietary
concentrations
corresponded
to
doses
of
4.67,
31.34,
and
92.43
mg/
kg/
day
for
F0
males;
0,
5.56,
36.32,
and
110.78
mg/
kg/
day
for
F0
females;
0,
5.79,
23.49,
and
124.33
mg/
kg/
day
for
F1
males;
and
0,
6.41,
26.91,
and
135.54
mg/
kg/
day
for
F1
females
averaged
over
the
premating
period.
Each
group
received
treated
or
control
diet
continuously
for
70
days
prior
to
mating
and
during
mating,
gestation,
and
lactation
of
one
litter
per
generation.
F1
pups
selected
to
parent
the
F2
generation
were
weaned
onto
the
same
food
as
their
parents.
Parental
males
were
sacrificed
after
delivery
of
their
litters
and
parental
females
were
sacrificed
after
weaning
of
their
litters.
No
treatment
related
deaths,
clinical
signs,
organ
weight
changes,
gross
lesions,
or
26
microscopic
lesions
were
observed
in
adult
rats
of
either
generation.
No
treatment
related
effects
were
observed
on
body
weights,
weight
gain,
feed
consumption,
or
food
efficiency
in
75
or
300
ppm
group
F0
or
F1
male
or
female
rats
at
any
time
during
the
study
including
the
gestation
and
lactation
periods
of
the
females.
F0
and
F1
male
and
female
rats
fed
the
1500
ppm
diet
weighed
significantly
(p<
0.01
or
<0.05)
less
and
gained
less
weight
during
the
premating
period.
The
F0
males
weighed
5
6%
less
than
controls
during
premating,
gained
14
23%
less
weight
during
three
weekly
intervals
up
to
day
45,
and
gained
9%
less
weight
over
the
entire
premating
period;
they
also
gained
8%
less
weight
than
controls
over
the
mating/
postmating
period.
The
F1
males
weighed
10
19%
less
than
controls
during
the
entire
study,
gained
16%
and
11%
less
weight
during
the
first
two
weekly
intervals,
and
gained
8%
less
weight
than
controls
averaged
over
the
entire
premating
period.
The
F0
females
weighed
4
5%
less
than
controls
during
the
first
42
days
of
premating,
gained
27%
less
weight
during
the
first
week,
and
7%
(N.
S.)
less
averaged
over
the
entire
premating
period.
The
F1
females
weighed
8
22%
less
than
controls
throughout
premating
and
gained
9%
less
weight
during
the
first
week;
weight
gain
for
the
remaining
weekly
intervals
and
for
the
entire
premating
period
was
similar
to
that
of
controls.
Food
consumption
and
food
efficiency
for
F0
and
F1
rats
followed
patterns
similar
to
that
of
body
weight
and
weight
gain;
the
largest
difference
between
the
1500
ppm
groups
and
controls
occurred
during
the
early
part
of
the
premating
period.
When
averaged
over
the
entire
premating
period,
F0
and
F1
males
consumed
6
7%
less
food
than
control
and
had
food
efficiency
values
similar
to
those
of
the
controls.
Feed
consumption
and
food
efficiency
for
the
F0
females
were
similar
to
those
of
the
control
group,
whereas
F1
females
consumed
9%
(p<
0.01)
less
feed
and
had
a
food
efficiency
value
10%
(p<
0.01)
greater
than
that
of
controls.
F0
and
F1
females
in
the
1500
ppm
group
weighed
less
and
gained
less
weight
than
controls
during
gestation,
with
the
effect
being
greater
in
the
F1
females.
During
lactation
weight
gain
was
markedly
reduced
in
F1
females
during
the
first
4
days,
but
was
greater
than
that
of
controls
averaged
over
the
entire
lactation
period.
The
lowest
observed
effect
level
(LOAEL)
for
parental
systemic
toxicity
is
1500
ppm
(92.43
124.33
mg/
kg/
day
for
males
and
110.78
135.54
mg/
kg/
day
for
females)
based
on
decreased
body
weight,
weight
gain,
and
feed
consumption.
The
no
observed
adverseeffect
(NOAEL)
level
is
300
ppm
(23.49
31.34
mg/
kg/
day
for
males
and
26.91
36.32
mg/
kg/
day
for
females).
No
treatment
related
effects
were
observed
on
the
estrous
cycle
of
either
F0
or
F1
females
at
any
dose
level
or
on
percent
motile
sperm,
sperm
count,
percent
progressively
motile
sperm,
epididymal
sperm
count,
spermatid
head
count,
daily
sperm
production,
or
efficiency
of
daily
sperm
production
in
F0
or
F1
males
at
any
dose
level.
There
was
a
dose
related
increase
in
the
percentage
of
abnormal
sperm
in
the
treated
males
but
no
statistical
significance
at
any
dose
level.
No
treatment
related
gross
or
microscopic
effects
were
observed
in
male
or
female
rats
of
either
generation.
No
treatment
related
effects
were
observed
on
any
parameter
of
reproductive
performance
including,
mating
and
fertility
indexes,
gestation
index,
pregnancy
index,
precoital
duration,
gestation
length,
or
number
of
females
producing
live
litters.
27
The
LOAEL
for
reproductive
toxicity
could
not
be
established
because
no
effects
were
observed
at
any
dose
level;
therefore,
the
NOAEL
is
$
1500
ppm
(92.43
124.33
mg/
kg/
day
for
males
and
110.78
135.54
mg/
kg/
day
for
females).
No
treatment
related
effects
were
observed
on
implantation
sites/
litter,
number
of
live
pups
born/
litter,
number
of
dead
pups
born/
litter,
live
birth
index,
sex
ratio,
clinical
signs,
or
organ
weight
or
necropsy
findings
in
pups
surviving
to
21
days.
Pup
survival
was
decreased
at
300
and
1500
ppm
for
both
generations.
Increased
number
of
deaths
in
the
F2
generation
males
and
females
resulted
in
an
18
19%
decrease
in
mean
litter
size
on
postnatal
day
4
(p<
0.01
or
<0.05)
and
decreased
viability
and
lactation
indexes
at
1500
ppm.
A
large
number
of
pups
that
died
had
no
milk
in
their
stomachs.
In
addition,
pup
weight/
litter
and
pup
weight
gain
in
the
1500
ppm
group
pups
were
reduced
for
both
generations
starting
with
postnatal
day
4
(11
15%
for
F1
and
13
23%
for
F2
pups);
body
weight
gain
was
reduced
throughout
lactation
with
the
greatest
effect
occurring
during
the
first
7
days
for
F1
pups
and
the
first
14
days
for
F2
pups.
Sexual
maturation
was
delayed
in
1500
ppm
group
F1
offspring
as
evidenced
by
delayed
balanopreputial
separation
in
the
males
(+
2.1
days)
and
vaginal
patency
in
the
females
(+
1.4
days).
The
differences
remained
statistically
significant
after
adjustment
for
body
weight
decreases.
Anogenital
distance
was
significantly
reduced
in
F2
male
pups
in
the
1500
ppm
group,
but
not
when
the
distance
was
adjusted
for
body
weight.
The
LOAEL
for
offspring
toxicity
was
300
ppm
(23.49
31.34
mg/
kg/
day
for
males
and
26.91
36.32
mg/
kg/
day
for
females)
based
on
increased
numbers
of
F2
pups
with
no
milk
in
the
stomach
and
decreased
pup
survival.
The
NOAEL
is
75
ppm
(4.67
5.79
mg/
kg/
day
for
males
and
5.56
6.41
mg/
kg/
day
for
females).
This
study
is
Acceptable/
Guideline
and
satisfies
the
guideline
requirement
for
a
twogeneration
reproductive
study
(OPPTS
870.3800;
OECD
416)
in
the
rat.
5.5
Developmental
Neurotoxicity
(Executive
Summary
has
been
revised
based
on
new
morphometric
measurements
from
MRID
45456701)
In
a
developmental
neurotoxicity
study
(MRID
#
44393701,
45456701,
45456702,
45456703),
26
pregnant
female
Sprague
Dawley
rats/
group
were
administered
carbaryl
(99.1%
a.
i.)
by
gavage
from
Gestation
Day
(GD)
6
through
Lactation
Day
(LD)
10
at
doses
of
either
0,
0.1,
1.0
or
10
mg/
kg/
day.
An
additional
6
pregnant
females/
group
were
dosed
at
the
same
levels
for
the
cholinesterase
(ChE)
phase
of
the
study.
ChE
measurements
were
done
pre
dosing
(GD
6)
and
post
dosing
at
time
of
peak
effect
(1
hour
post
dosing)
on
GD
6,
15
and
20
and
LD
4
and
10.
Functional
Observational
Battery
(FOB)
measurements
were
performed
at
approximately
0.5
and
2
hours
post
dosing
on
the
same
days
as
body
weight
measurements
during
the
dosing
period
(GD
0,
6,
9,
12,
15,
18
and
20
and
LD
4,
7,
11,
13
and
21).
Measures
of
reproductive
performance
were
evaluated.
Offspring
were
examined
for
body
weight,
physical
development
landmarks
(tooth
eruption
and
eye
opening),
FOB
assessments
(days
4,
7,
11,
13,
17
and
21)
and
motor
activity
(days
13,
17
and
21).
On
LD
11,
1
animal/
sex/
litter
was
sacrificed
for
brain
weights;
of
these,
six/
sex
were
randomly
selected
for
neuropathological
evaluation.
The
eyes
from
all
dose
groups
were
examined.
After
LD
21,
28
3
animals/
sex/
litter
were
separated
from
the
dams
and
constituted
the
F1
adult
generation.
These
animals
were
evaluated
for
body
weight,
physical
development
(vaginal
opening
and
preputial
separation),
motor
activity
(day
60),
startle
habituation
response
(days
22
and
60),
passive
avoidance
(day
23)
and
water
maze
behavior
(day
60).
After
completion
of
the
behavior
test
period
(at
approximately
10
weeks
of
age),
12
animals/
sex/
group
were
anesthetized
and
perfused
for
post
mortem
examination.
Tissues
from
6
animals/
sex
of
the
control
and
high
dose
group
were
processed
for
neuropathological
evaluation
and
morphometric
measurements;
the
eyes
from
the
low
and
mid
dose
group
of
all
perfused
animals
were
examined.
For
the
F0
generation
animals,
there
were
no
carbaryl
associated
deaths.
No
treatment
related
clinical
signs
of
toxicity
were
observed.
There
was
a
statistically
significant
decrease
(92%)
in
body
weight
gain
for
females
in
the
10
mg/
kg/
day
group
for
the
period
GD
6
9.
Unfortunately,
food
consumption
was
not
measured
during
the
study.
During
the
FOB
measurements,
the
incidence
of
females
in
the
10
mg/
kg/
day
group
with
decreased
pupil
size
(pinpoint
pupils)
was
increased
on
all
occasions
during
the
dosing
period.
An
increased
incidence
of
dams
with
slight
tremors
affecting
the
head,
body
and/
or
limbs
was
noted
on
the
majority
of
assessment
occasions
in
the
dosing
period.
There
were
also
occasional
occurrences
of
ataxic
gait/
overall
gait
incapacity
which
was
considered
to
be
of
toxicological
significance
due
to
other
effects
upon
gait.
For
the
10
mg/
kg/
day
group,
RBC
and
whole
blood
ChE
levels
were
statistically
significantly
decreased
(28%
and
32
34%,
respectively)
on
GD
20
and
LD
10.
Although
the
plasma
ChE
levels
were
not
statistically
significantly
altered,
the
percentage
decreases
on
GD
20,
LD
4
and
LD
10
were
32
39%.
Brain
ChE
levels
were
statistically
significantly
decreased
(42%).
There
were
no
treatment
related
effects
on
gross
necropsy
findings
for
the
F0
generation
animals.
There
were
no
effects
observed
on
maternal
performance
parameters
of
pregnancy
rate,
gestation
index,
length
of
gestation,
numbers
of
live
pups,
dead
or
malformed
pups,
implantation
scars,
sex
ratio
or
post
implantation
loss.
There
was
a
slight
(P>
0.05)
increase
in
the
number
of
dead
pups
in
the
10
mg/
kg/
day
group,
however
the
value
was
within
the
historical
control
range
for
this
strain.
For
the
F1
generation
pups,
there
were
no
treatment
related
effects
on
pup
weight,
pup
survival
indices,
developmental
landmarks
(tooth
eruption
and
eye
opening),
FOB
measurements
or
motor
activity
assessments.
At
sacrifice
on
LD
11,
there
were
no
treatmentrelated
effects
on
brain
weight
and
gross
or
microscopic
pathology.
Significant
differences
noted
in
the
morphometric
measurements
included
an
increase
in
Line
B
of
the
right
forebrain
and
Line
F
of
the
left
cerebellum
in
the
10
mg/
kg/
day
males.
In
the
10
mg/
kg/
day
females,
Line
F
through
both
the
right
and
left
cerebellum
was
decreased
(15%
and
22%,
respectively).
For
the
F1
generation
adults,
there
were
no
treatment
related
effects
on
clinical
condition,
body
weight,
physical
development
(vaginal
opening
and
preputial
separation),
motor
activity,
auditory
startle
response,
passive
avoidance
and
water
maze
measurements.
At
sacrifice,
there
were
no
gross
or
microscopic
neuropathological
lesions
observed
for
animals
examined
in
this
study
that
were
attributable
to
treatment
with
the
test
article.
There
was
an
increased
incidence
of
retinal
fold/
rosette
in
the
10
mg/
kg/
day
group
(1/
12
for
control
vs.
4/
12
for
males;
0/
12
for
control
vs.
2/
12
for
females).
The
finding
was
not
considered
of
toxicological
significance
since
the
incidence
was
within
the
historical
control
range
for
10
Personal
communication
with
Robert
Chapin,
one
of
the
study
authors
29
males,
occurred
at
a
low
rate
and
was
not
dose
dependent.
For
the
morphometric
measurements,
there
was
a
significant
bilateral
decrease
in
Line
A
through
the
forebrain
(7.7
9.8%)
and
a
significant
increase
in
Line
F
through
the
right
cerebellum
of
the
10
mg/
kg/
day
males.
Increases
originally
noted
in
the
10
mg/
kg
adult
females
in
Line
G,
width
of
the
cerebellum,
were
found
to
be
based
on
erroneous
measurements,
and
additional
measures
were
submitted.
Now,
for
the
10
mg/
kg/
day
females,
there
were
significant
bilateral
increases
in
Line
F
through
the
cerebellum
(7.4
15%).
Measurements
of
the
size
of
the
thickness
of
lobes
and
of
the
granule
cell
layers
of
the
cerebellum
in
high
dose
pups
and
adults
did
not
differ
from
those
of
controls.
While
additional
statistical
analyses
by
the
registrant
indicated
no
treatment
related
effects,
HED's
additional
statistical
analyses
did
indicate
treatment
related
effects.
The
maternal
toxicity
LOAEL
was
10
mg/
kg/
day
based
on
decreased
body
weight
gain,
alterations
in
Functional
Observational
Battery
measurements
and
RBC,
plasma,
whole
blood
and
brain
cholinesterase
inhibition.
The
maternal
NOAEL
was
1.0
mg/
kg/
day.
The
developmental
neurotoxicity
LOAEL
was
10
mg/
kg/
day
based
bilateral
decrease
in
the
size
of
the
forebrain
(Line
A)
in
adult
males
(7.7
9.8%);
a
bilateral
decrease
in
the
length
of
the
cerebella
(Line
F)
in
female
pups
(15
22%);
and
a
bilateral
increase
in
the
length
of
the
cerebella
(Line
F)
in
female
adults
(7.4
15%).
The
developmental
NOAEL
was
1.0
mg/
kg/
day.
Morphometric
assessment
at
the
mid
and
low
doses
could
not
be
conducted
due
to
inadequate
tissue
storage;
however,
based
on
the
minimal
findings
at
the
LOAEL,
it
is
HED's
judgment
that
effects
would
be
unlikely
to
occur
at
1
mg/
kg/
day,
which
is
10%
of
the
LOAEL.
This
developmental
neurotoxicity
study
is
classified
acceptable
and
does
satisfy
the
guideline
requirement
for
a
developmental
neurotoxicity
study
(OPPTS
870.6300)
in
rats.
5.6
Additional
Information
from
Literature
Sources
In
an
unpublished
study
from
the
National
Health
and
Ecological
Effects
Research
Laboratories,
EPA,
and
the
National
Institute
for
Environmental
Health
Sciences/
National
Toxicology
Program,
pregnant
Sprague
Dawley
rats
(n=
36
or
38)
were
dosed
by
gavage
with
carbaryl
at
doses
of
0,
6,
12
or
25
mg/
kg/
day.
10
The
following
description
of
the
study
design
and
findings
was
extracted
from
tables
and
posters
discussing
various
aspects
of
the
study.
The
dams
were
dosed
from
gestational
day
(GD)
14
to
postnatal
day
(PND)
7,
after
which
the
pups
were
directly
dosed
with
the
same
dose
levels
until
PND
21
(weaning)
or
PND
42.
Analyses
for
carbaryl
and
1
naphthol
in
the
dam's
plasma
and
milk
and
pup's
plasma
were
performed.
A
sample
of
milk
was
incubated
with
a
preparation
of
rat
brain
to
provide
a
bioassay
of
ChE
activity.
The
brains
were
taken
from
a
dam
and
two
fetuses
sacrificed
at
various
times
after
dosing
on
GD
18
to
measure
ChE.
Some
pups
(n=
4
6/
dose/
sex)
were
sacrificed
on
PND
1,
7,
21
and
47
and
body
and
brain
weights
recorded.
FOB
and
motor
11
Pant
N,
Shankar
R,
Srivastava
SP
(1996).
Spermatotoxic
effects
of
carbaryl
in
rats.
Human
Exp
Toxicol
15(
9);
736
38.
30
activity
were
measured
on
PND
26/
27,
47/
48,
62/
63
and
81/
82.
In
the
post
weaning
period,
cognitive
function
was
evaluated
using
a
simple
test
of
associative
learning,
passive
avoidance,
and
in
adulthood
by
assessing
between
session
habituation
of
motor
activity.
Sperm
counts,
organ
weights
and
clinical
pathology
were
done
on
males
at
necropsy.
Carbaryl
or
1
naphthol
were
not
present
in
the
pups'
plasma
above
the
limit
of
detection
at
any
exposure
concentration.
In
the
dams'
plasma,
carbaryl
was
below
the
limit
of
detection
for
the
6
mg/
kg/
day
dose,
but
was
present
in
some
or
most
of
the
animals
from
the
other
two
doses.
1
naphthol
was
present
in
all
treated
groups
in
a
dose
related
increase.
In
general,
milk
concentrations
followed
the
trends
seen
in
plasma,
however
1
napthol
was
about
3
5
times
lower
in
milk
compared
to
plasma.
There
was
a
dose
related
suppression
of
brain
ChE
produced
by
the
blood
samples.
There
was
a
dose
related
decrease
in
ChE
activity
in
the
brain
and
blood
of
dams
at
GD
19,
and
fetuses
taken
at
that
time
also
showed
a
very
similar
level
of
inhibition
in
fetal
brain.
There
was
a
decrease
in
the
number
of
live
pups/
litter
in
the
25
mg/
kg/
day
group
at
PND
0,
7,
and
21.
The
average
pup
weight
was
decreased
in
the
25
mg/
kg/
day
group
at
PND
1,
7,
14
and
21.
There
were
no
changes
in
cognitive
function.
For
brain
weights
measured
on
PND
0,
7,
21
and
47,
the
only
change
was
on
PND
21
when
the
25
mg/
kg/
day
group
was
decreased
in
males
and
the
low
and
high
dose
groups
were
decreased
in
females.
Equivocal
changes
in
FOB
parameters
were
observed
in
males
at
PND62/
63
and
in
females
at
PND
47/
48.
There
were
no
evidence
of
an
effect
on
the
necropsy
parameters.
In
a
1996
study
in
the
open
literature,
carbaryl
was
administered
to
four
groups
of
6
young
and
6
adult
Druckery
albino
rats
per
group
at
doses
of
0,
25,
50
or
100
mg/
kg/
day
for
60
days.
11
Body
weight
was
recorded
at
initiation
and
completion
of
the
study.
On
the
61st
day,
the
animals
were
sacrificed
and
the
testes,
epididymides,
seminal
vesicles,
ventral
prostrate
and
coagulating
glands
were
weighed.
Epididymal
sperm
were
used
for
sperm
counts
and
examination
of
motility
and
morphology.
No
overt
toxicity
or
mortality
was
observed.
There
were
dose
related
effects
on
body
weight
for
the
50
and
100
mg/
kg/
day
groups.
The
absolute
weights
of
the
testes,
epididymides,
seminal
vesicle,
ventral
prostrate
and
coagulating
glands
were
significantly
decreased
at
100
mg/
kg/
day
for
young
rats.
The
relative
organ
weights
were
not
affected
at
any
doses.
The
organ
weights
were
not
affected
in
adult
animals.
Young
rats
receiving
carbaryl
50
mg/
kg/
day
had
a
24.4%
and
25%
decrease
in
sperm
motility
and
sperm
count,
respectively;
the
changes
at
100
mg/
kg/
day
were
42.9%
and
37.5%,
respectively.
Adults
receiving
the
50
mg/
kg/
day
dose
had
a
15.1%
and
12.5%
reduction
in
sperm
motility
and
count,
respectively;
the
changes
at
100
mg/
kg/
day
were
26.4%
and
25%,
respectively.
The
percentage
of
young
rats
with
abnormal
sperm
was
19.8%
and
33.7%
at
50
and
100
mg/
kg/
day,
respectively.
In
adults,
the
percentages
were
16.1%
and
23.1%
for
the
respective
doses.
In
another
study
from
this
laboratory,
three
groups
of
8
male
Wistar
rats
per
group
were
12
Pant
N,
Srivastava
SC,
Prasad
AK,
Shankar
R,
Srivastava
SP
(1995).
Effects
of
Carbaryl
on
the
Rat's
Male
Reproductive
System.
Vet
Human
Toxicol
37(
5):
421
425.
13
Narotsky
MG,
Kavlock
RJ
(1995).
A
Multidisciplinary
Approach
to
Toxicological
Screening:
II.
Developmental
Toxicity.
Journal
of
Toxicology
and
Environmental
Health
45:
145
171.
31
administered
carbaryl
by
gavage
at
doses
of
0,
50
or
100
mg/
kg/
day
for
90
days.
12
Body
weight
was
measured
periodically
throughout
the
study.
On
the
91st
day,
the
animals
were
sacrificed
and
the
male
reproductive
glands
were
weighed.
One
testis
from
each
animal
was
preserved
for
histopathology
and
the
other
was
homogenized
for
testicular
enzyme
assay.
Epididymal
sperm
were
used
for
sperm
counts
and
examination
of
motility
and
morphology.
No
clinical
signs
of
toxicity
were
observed,
except
for
lethargy.
Body
weights
were
decreased
in
the
100
mg/
kg/
day
group
after
60
days.
There
were
no
changes
in
the
weights
of
reproductive
organs.
There
were
significant
changes
in
the
testicular
enzymes
of
the
100
mg/
kg/
day
group:
decreases
in
SDH
and
G6PDH
and
increases
in
GGT
and
LDH.
At
both
doses,
there
were
significant
decreases
in
the
total
epididymal
sperm
count,
percent
sperm
motility
and
increases
in
the
percent
with
morphological
abnormalities
in
head,
neck
and
tail.
At
50
mg/
kg/
day,
the
testes
had
slight
to
moderate
congestion
and
edema.
A
few
tubules
showed
moderately
depressed
spermatogenesis
and
loss
of
sperm.
There
was
moderate
atrophy
of
seminiferous
tubules
with
prominent
interstitial
spaces
in
the
center
of
the
testes,
but
the
Leydig
cells
were
intact.
At
100
mg/
kg/
day,
there
were
increases
in
the
intensity
of
congestion
and
the
edematous
reaction
was
seen
both
peripherally
and
in
the
central
region.
Most
of
the
seminiferous
tubules
had
disturbed
spermatogenesis
as
well
as
accumulations
of
cellular
masses
in
their
lumens.
In
a
study
conducted
at
EPA's
Health
Effects
Research
Laboratory,
16
pregnant
Fischer
344
rats
were
administered
carbaryl
by
gavage
on
gestation
days
(GD)
6
19
at
doses
of
78
or
104
mg/
kg/
day;
21
control
animals
were
used.
13
The
high
dose,
selected
to
produce
overt
maternal
toxicity,
was
based
on
the
results
of
a
14
day
repeated
dose
study
in
nonpregnant
female
rats.
The
low
dose
was
75%
of
the
high
dose.
Maternal
body
weights
were
determined
on
GD
6,
8,
10,
13,
16
and
20.
All
rats
were
examined
periodically
for
clinical
signs
of
toxicity.
Pups
in
each
litter
were
examined
and
counted
on
postnatal
day
(PD)
1,
3,
and
6
and
weighed
collectively
on
PD
1
and
6.
After
the
final
litter
examination,
the
dams
were
killed
and
uterine
implantation
sites
counted.
Females
that
did
not
deliver
by
GD
24
were
killed
and
their
uteri
examined
for
pregnancy
status.
Clinical
signs
of
toxicity
observed
in
the
dams
included
tremors,
motor
depression,
and
lacrimation,
usually
during
the
first
three
days
of
treatment.
Jaw
clonus
was
observed
throughout
the
treatment
period.
(The
article
does
not
indicate
if
clinical
signs
were
observed
at
both
doses.)
Marked
weight
loss
was
observed
early
in
treatment.
Over
the
entire
treatment
period,
carbaryl
produced
extrauterine
weight
loss
at
the
high
dose
and
reduced
weight
gains
at
the
low
dose.
There
was
increased
prenatal
mortality
at
the
high
dose;
this
effect
was
attributed
to
two
(15%)
fully
resorbed
litters
in
this
group.
In
addition,
high
dose
pup
weights
were
significantly
reduced
on
PD
1.
The
PD
1
pup
weights
in
the
low
dose
and
the
PD
6
pup
weights
in
both
carbaryl
exposed
groups
were
also
significantly
reduced,
but
only
when
analyzed
using
the
number
of
live
pups
on
PD
1
as
the
14
Savitz
DA,
Arbuckle
T,
Kaczor
D,
Curtis
KM
(1997).
Male
Pesticide
Exposure
and
Pregnancy
Outcome.
Am
J
Epidemiol
146(
12):
1025
36.
32
covariate.
In
a
recent
epidemiology
study,
the
effects
of
exposure
of
male
farmers
in
Ontario,
Canada,
to
agricultural
pesticides
and
pregnancy
outcome
was
investigated.
14
Miscarriage
risk
was
not
associated
with
participation
in
farm
activities
for
all
types
of
chemical
applications,
but
was
increased
in
combination
with
reported
use
of
thiocarbamates,
carbaryl
and
unclassified
pesticides
on
the
farm
(Odds
ratio
=
1.9,
95%
C.
I.
1.1
3.1).
There
was
no
association
between
use
of
carbaryl
and
preterm
delivery,
small
for
gestational
age
or
altered
sex
ratio
measurements.
At
the
1996
Joint
Meeting
on
Pesticide
Residues
(JMPR),
it
was
concluded
that
carbaryl
induces
developmental
toxicity,
manifested
as
deaths
in
utero,
reduced
fetal
weight,
and
malformations,
but
only
at
doses
that
cause
overt
maternal
toxicity.
The
shortcomings
of
the
developmental
studies
made
them
inadequate
for
identifying
NOAELs
for
developmental
toxicity
that
could
be
used
for
assessing
risk
under
conditions
of
exposure
other
than
in
the
diet.
The
Committee
recommended
studies
of
teratogenicity
in
rats
and
rabbits
and
study
of
developmental
neurotoxicity
and/
or
screening
for
acute
or
subchronic
neurotoxicity.
Two
dog
studies
were
cited
in
the
report.
In
these
studies,
maternal
toxicity
(dystocia,
at
parturition
only)
was
observed
at
a
dose
of
3.1
mg/
kg/
day.
Various
birth
defects
were
observed
in
the
pups
at
doses
$
5
mg/
kg/
day.
Thus
the
LOAEL
for
maternal
toxicity
was
3.1
mg/
kg/
day,
which
was
the
NOAEL
for
birth
defects
in
the
offspring.
The
report
states
that
studies
on
reproductive
toxicity
were
conducted
some
time
ago
and
had
some
deficiencies
in
relation
to
currently
acceptable
scientific
standards.
The
Meeting
recommended
that
a
new
two
generation
reproductive
toxicity
study
should
be
carried
out
on
rats,
with
special
attention
to
the
male
reproductive
system
since
effects
on
this
system
were
observed
in
some
long
term
studies
of
toxicity
at
gavage
doses
significantly
lower
than
those
evaluated
in
the
dietary
studies
of
reproductive
toxicity.
5.7
Determination
of
Susceptibility
There
was
no
evidence
of
quantitative
or
qualitative
susceptibility
following
in
utero
exposures
in
developmental
studies
in
the
rat
and
rabbit.
In
the
reproduction
study,
there
was
evidence
of
quantitative
susceptibility
of
offsprings.
The
LOAEL
for
parental
systemic
toxicity
was
based
on
decreased
body
weight,
weight
gain,
and
feed
consumption;
the
NOAEL
was
27
mg/
kg/
day
in
males
and
30
mg/
kg/
day
in
females.
In
the
offspring
the
LOAEL
was
based
on
increased
numbers
of
F2
pups
with
no
milk
in
the
stomach
and
decreased
pup
survival;
the
NOAEL
was
5
mg/
kg/
day
in
males
and
6
mg/
kg/
day
in
females.
No
adverse
effects
were
observed
in
the
reproductive
parameters;
the
NOAEL
was
the
highest
dose
tested.
33
In
the
developmental
neurotoxicity
study,
there
was
evidence
of
qualitative
susceptibility.
For
maternal
toxicity,
the
LOAEL
was
based
on
decreased
body
weight
gain,
alterations
in
Functional
Observational
Battery
measurements
and
inhibition
of
plasma,
whole
blood
and
brain
cholinesterase
activity;
the
NOAEL
was
1
mg/
kg/
day.
For
developmental
neurotoxicity,
the
LOAEL
was
based
on
the
morphometric
changes
seen
in
the
brain
of
the
offsprings;
the
NOAEL
was
1
mg/
kg/
day.
5.8
Degree
of
Concern
Analysis
and
Residual
Uncertainties
The
HIARC
concluded
that
there
is
no
residual
concern
in
the
two
generation
reproduction
study
because
the
dose
response
effects
in
pups
are
well
characterized
and
the
NOAEL
for
the
offspring
effects
is
above
that
was
used
for
establishing
the
chronic
Reference
Dose
(RfD)
for
chronic
dietary
risk
assessment.
The
HIARC
selected
the
LOAEL
of
3.1
mg/
kg/
day
established
in
the
chronic
toxicity
study
in
dogs
for
establishing
the
chronic
RfD.
Since
a
LOAEL
was
used,
an
additional
uncertainty
factor
of
3X
was
applied
(i.
e,
lack
of
a
NOAEL)
to
the
LOAEL.
Although
a
NOAEL
was
not
established
in
this
study,
the
HIARC
determined
that
a
3X
was
adequate
(as
opposed
to
a
higher
value)
because:
1)
cholinesterase
inhibition
in
females
was
not
accompanied
by
clinical
signs;
2)
no
inhibition
was
seen
for
any
cholinesterase
compartment
in
males
at
this
dose;
3)
the
magnitude
of
inhibition
of
plasma
cholinesterase
inhibition
(12
23%
decrease)
was
comparable
to
the
magnitude
of
inhibition
(22%)
seen
in
the
5
week
study
in
dogs
indicating
no
cumulative
effects
following
long
term
exposure;
4)
the
study
was
wellconducted
and
there
are
sufficient
data
from
subchronic
and
chronic
duration
studies
in
the
other
species
which
support
cholinesterase
inhibition
as
the
critical
effect.
In
addition,
based
on
the
cholinesterase
inhibition
data,
the
dog
appears
to
be
more
sensitive
than
the
rat
in
long
term
studies.
Furthermore,
use
of
the
LOAEL
of
3
mg/
kg/
day
from
the
1
year
dog
study
with
an
uncertainty
factor
of
300
results
in
a
NOAEL
of
1
mg/
kg/
day.
This
extrapolated
NOAEL
is
identical
to
that
of
the
offspring
NOAEL
of
1.0
mg/
kg/
day
established
in
the
the
developmental
neurotoxicity
study.
Thus,
the
NOAEL
of
1
mg/
kg/
day
used
for
establishing
the
chronic
RfD
is
below
the
NOAEL
of
5
mg/
kg/
day
for
offspring
toxicity
and
the
chronic
RfD
would
be
protective
of
the
effects
of
concern
for
infants
and
children
following
chronic
dietary
exposures.
With
regard
to
the
developmental
neurotoxicity
study,
the
HIARC
concluded
that
there
was
a
low
level
of
concern
based
on
the
following
residual
uncertainties
°
The
first
uncertainty
was
the
lack
of
a
demonstrated
effect
level
since
morphometric
measurements
of
brains
in
the
offsprings
were
not
performed
at
the
mid
dose
(1
mg/
kg/
day).
However,
this
concern
was
negated
since
even
at
the
high
dose
of
10
mg/
kg/
day,
the
morphometric
changes
were
minimal
and
therefore,
it
is
unlikely
that
adverse
effects
would
be
seen
at
1
mg/
kg/
day,
which
is
10%
of
the
LOAEL.
°
The
second
uncertainty
was
the
lack
of
comparative
data
in
adults
and
offspring
for
cholinesterase
inhibition.
This
concern
was
negated
since
no
FOB
alterations
were
seen
in
pups.
Other
studies
in
the
data
base
have
shown
that
when
FOB
alterations
34
were
seen
in
adult
animals,
they
are
usually
accompanied
with
cholinesterase
inhibition.
Also,
the
results
of
the
National
Institute
for
Environmental
Health
Sciences
study
(discussed
below)
showed
no
difference
in
cholinesterase
inhibition
in
pups
and
adults.
There
was
a
dose
related
decrease
in
cholinesterase
activity
in
the
brain
and
blood
of
dams
at
gestation
day
19
and
fetuses
taken
at
this
time
also
showed
a
very
similar
level
in
fetal
brain
cholinesterase.
The
HIARC
concluded,
that
the
NOAEL
of
1
mg/
kg/
day
selected
for
establishing
the
acute
RfD
would
address
the
low
level
of
concern
for
the
residual
concerns
and
would
be
protective
of
the
effects
of
concern
for
infants
and
children
following
a
single
oral
exposure.
5.9
Hazard
Based
Special
FQPA
Safety
Factor
Recommendation
The
HIARC
concluded
that
the
hazard
based
special
FQPA
safety
factor
should
be
reduced
to
1x
based
on
the
following
reasons:
1.
The
toxicology
database
is
complete
2.
There
was
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
in
rat
or
rabbit
fetuses
following
in
utero
exposures
3.
There
was
evidence
of
qualitative
susceptibility
and
a
low
level
of
concern
due
to
some
residual
uncertainties
in
the
developmental
neurotoxicity
study.
However,
as
discussed
in
Section
I.
3,
the
acute
RfD
would
address
these
residual
uncertainties
and
would
be
protective
of
the
pre
pre/
post
natal
toxicity
following
an
acute
dietary
exposure.
4.
There
was
evidence
of
increased
susceptibility
in
the
offsprings
in
the
two
generation
reproduction
study,
but
there
was
no
residual
uncertainties.
The
chronic
RfD
would
be
protective
of
the
pre
pre/
post
natal
toxicity
following
chronic
dietary
exposures.
5.
The
dose
selected
for
residential
exposures,
would
be
protective
of
the
pre
pre/
post
natal
toxicity
following
non
dietary
exposures.
35
6.
HAZARD
CHARACTERIZATION
Carbaryl
is
a
carbamate
insecticide.
Its
mode
of
toxic
action
is
through
plasma,
RBC
and
brain
cholinesterase
inhibition
(ChEI).
In
most
studies
in
which
ChE
was
measured,
it
was
the
endpoint
used
for
setting
the
NOAEL.
Carbaryl
is
relatively
acutely
toxic
by
the
oral
route
(Toxicity
Category
II)
but
non
toxic
acutely
by
the
dermal
and
inhalation
routes.
It
is
not
a
dermal
or
eye
irritant
or
a
dermal
sensitizer.
Carbaryl
was
negative
for
delayed
neurotoxicity
in
the
hen.
Clinical
signs
compatible
with
ChEI
were
seen
in
most
of
the
short
and
long
term
studies
in
rodents
and
non
rodents.
There
was
no
evidence
of
structural
neuropathology
in
the
acute
and
subchronic
neurotoxicity
studies
in
rats.
In
the
developmental
neurotoxicity
study
in
the
rat,
changes
in
brain
morphometric
measurements
were
observed
in
female
offspring;
however,
their
toxicological
significance
is
unknown.
Carbaryl
has
been
classified
as
a
Likely
to
be
carcinogenic
to
humans
based
on
an
increased
incidence
of
hemangiosarcomas
and
combined
hemangiomas/
hemangiosarcomas
in
CD
1
mice
at
100
ppm
(15
mg/
kg/
day)
and
above.
Other
tumors,
including
kidney
tubular
cell
tumors
in
male
mice,
liver
tumors
in
female
mice,
thyroid
tumors
in
male
rats,
bladder
tumors
in
male
and
female
rats
and
liver
tumors
in
female
rats
were
observed
at
excessive
doses.
Mechanistic
metabolism
studies
were
considered
inadequate
to
demonstrate
a
mode
of
action
for
the
vascular
tumors.
The
default
linear
extrapolation
will
be
used
for
risk
assessment;
the
Q1*
is
8.75
x
10
4
in
human
equivalents
based
on
the
based
on
the
mouse
vascular
tumors.
Maternal
toxicity
was
observed
at
the
same
dose
as
developmental
toxicity
in
both
the
rat
and
rabbit;
the
studies
showed
no
evidence
of
a
qualitative
or
quantitative
increased
susceptibility.
In
the
twogeneration
reproduction
study,
there
was
evidence
of
increased
quantitative
and
qualitative
susceptibility
of
offspring.
The
parental
NOAEL
level
was
approximately
27
mg/
kg/
day
for
males
and
30mg/
kg/
day
for
females)
based
on
decreased
body
weight,
weight
gain,
and
feed
consumption
at
approximately
108
mg/
kg/
day
for
males
and
124
mg/
kg/
day
for
females.
The
offspring
NOAEL
was
approximately
5
mg/
kg/
day
in
males
and
6
mg/
kg/
day
in
females
based
on
based
on
increased
numbers
of
F2
pups
with
no
milk
in
the
stomach
and
decreased
pup
survival
at
approximately
27
mg/
kg/
day
in
males
and
30
mg/
kg/
day
in
females.
In
the
developmental
neurotoxicity
study,
evidence
of
maternal
neurotoxicity
(FOB
alterations,
cholinesterase
inhibition)
was
observed
at
the
same
dose
as
changes
in
brain
morphometric
measurements
in
offspring.
7.
DATA
GAPS
90
day
inhalation
study
in
the
rat
with
cholinesterase
measurements
21
day
dermal
toxicity
study
in
the
rat
with
cholinesterase
measurements
Micronucleus
study
36
8.
ACUTE
TOXICITY
Acute
Toxicity
of
Carbaryl
Guideline
No.
Study
Type
MRIDs
#
Results
Toxicity
Category
81
1
Acute
Oral
rat
00148500
LD50
for
males
=
302.6
mg/
kg;
for
females
=
311.5
mg/
kg;
combined
=
301.0
mg/
kg
II
81
2
Acute
Dermal
rabbit
00148501
LD50
>
2000
mg/
kg
III
81
3
Acute
Inhalation
rat
00148502
LC50
>
3.4
mg/
L
IV
81
4
Primary
Eye
Irritation
00148503
not
a
primary
eye
irritant
IV
81
5
Primary
Skin
Irritation
00148504
not
a
primary
skin
irritant
IV
81
6
Dermal
Sensitization
00148505
negative
81
7
Acute
Delayed
Neurotoxi
city
(Hen)
*
negative
at
2000
mg/
kg
(approximate
LD50)
81
8
Acute
Neurotoxicity
rat
43845201
43845204
systemic
LOEL
=
10
mg/
kg
for
males
and
females
based
on
significant
inhibition
of
RBC,
plasma,
whole
blood
and
brain
cholinesterase;
NOEL
<
10
mg/
kg
*
Carpenter,
C.
P.,
Weil,
C.
S.,
Palm,
P.
E.,
Woodside,
N.
W.,
Nair,
J.
H.
and
Smyth,
H.
F.
Mammalian
Toxicity
of
1
napthyl
N
methyl
carbamate
(Sevin
Insecticide).
J.
Agric.
Food
Chem.
9(
1):
30
39,
1961.
37
9.
SUMMARY
OF
TOXICOLOGY
ENDPOINT
SELECTION
The
doses
and
toxicological
endpoints
selected
for
various
exposure
scenarios
for
Carbaryl:
EXPOSURE
SCENARIO
DOSE
(mg/
kg/
day)
ENDPOINT
STUDY
Acute
Dietary
NOAEL
=
1
UF
=
100
FOB
alterations
on
first
day
of
dosing
in
maternal
animals
Developmental
Neurotoxicity
rat
Acute
RfD
=
0.01
mg/
kg
Chronic
Dietary
LOAEL
=
3.1
UF
=
300
decrease
in
brain
cholinesterase
in
females
Chronic
toxicity
dog
Chronic
RfD
=
0.01
mg/
kg/
day
Short
Term
Oral
Incidental
NOAEL
=
1
FOB
alterations
on
first
day
of
dosing
in
maternal
animals
Developmental
Neurotoxicity
rat
IntermediateTerm
Oral
Incidental
Oral
NOAEL=
1.0
increased
incidence
of
FOB
changes;
decrease
in
RBC,
whole
blood,
plasma
and
brain
cholinesterase
subchronic
neurotoxicity
study
rat
Short
Term
(Dermal)
a
NOAEL
=
1
FOB
alterations
on
first
day
of
dosing
in
maternal
animals
Developmental
Neurotoxicity
rat
IntermediateTerm
(Dermal)
a
Oral
NOAEL=
1.0
increased
incidence
of
FOB
changes;
decrease
in
RBC,
whole
blood,
plasma
and
brain
cholinesterase
subchronic
neurotoxicity
study
rat
Long
Term
(Dermal)
a
LOAEL
=
3.1
decrease
in
brain
cholinesterase
in
females
chronic
toxicity
dog
Short
Term
(Inhalation)
b
NOAEL
=
1
FOB
alterations
on
first
day
of
dosing
in
maternal
animals
Developmental
Neurotoxicity
rat
Intermediate
Term
(Inhalation)
b
Oral
NOAEL=
1.0
increased
incidence
of
FOB
changes;
decrease
in
RBC,
whole
blood,
plasma
and
brain
cholinesterase
subchronic
neurotoxicity
study
rat
Long
Term
(Inhalation)
LOAEL
=
3.1
decrease
in
brain
cholinesterase
in
females
chronic
toxicity
dog
Cancer
Q1*
=
8.75
x
10
4
male
mouse
hemangiosarcoma
tumors
carcinogenicity
mouse
a
Since
an
oral
NOAEL/
LOAEL
was
selected,
a
dermal
absorption
factor
of
12.7%
should
be
used
in
route
to
route
extrapolation.
b
Since
an
oral
NOAEL
was
selected,
an
inhalation
factor
of
100%
should
be
used
in
route
to
route
extrapolation.
| epa | 2024-06-07T20:31:42.329750 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0009/content.txt"
} |
EPA-HQ-OPP-2002-0138-0010 | Supporting & Related Material | "2002-07-31T04:00:00" | null | TXR
NO.
0050634
April
3,
2002
MEMORANDUM
SUBJECT:
CARBARYL
3
rd
Reassessment
Report
of
the
FQPA
Safety
Factor
Committee.
NOTE:
THIS
REPORT
REPLACES
THE
PREVIOUS
REPORT
OF
THE
FQPA
SAFETY
FACTOR
COMMITTEE
DATED
APRIL
30,
2001
(HED
DOC.
NO.
014553).
FROM:
Carol
Christensen,
Acting
Executive
Secretary
And
Brenda
Tarplee,
Executive
Secretary
FQPA
Safety
Factor
Committee
Health
Effects
Division
(7509C)
THROUGH:
Ed
Zager,
Chairman
FQPA
Safety
Factor
Committee
Health
Effects
Division
(7509C)
TO:
Virginia
Dobozy,
Risk
Assessor
Reregistration
Branch
1
Health
Effects
Division
(7509C)
PC
Code:
056801
The
Health
Effects
Division
(HED)
FQPA
Safety
Factor
Committee
(SFC)
met
on
January
14,
2002
and
February
25,
2002
to
re
evaluate
the
hazard
and
exposure
data
for
Carbaryl
with
regard
to
making
a
decision
on
the
additional
safety
factor
for
the
protection
of
infants
and
children.
The
SFC
determined
that
reliable
data
demonstrate
that
the
safety
of
infants
and
children
will
be
protected
by
use
of
an
additional
safety
factor
of
3X.
This
report
replaces
the
previous
report
of
the
FQPA
Safety
Factor
Committee
dated
April
30,
2001
(HED
Doc.
No.
014553
).
2
I.
HAZARD
ASSESSMENT
(Correspondence:
V.
Dobozy
to
C.
Christensen
dated
February
25,
2002)
Since
the
last
FQPA
SFC
meeting
(April
30,
2001),
the
toxicology
data
base
for
Carbaryl
was
reevaluated
by
the
HED
Hazard
Identification
Assessment
Review
Committee
(HIARC)
on
December
18,
2001
and
February
19,
2002.
1.
Adequacy
of
the
Toxicology
Database
The
toxicology
data
base
for
Carbaryl
is
complete
for
FQPA
assessment.
There
are
acceptable
guideline
developmental
studies
in
the
rat
and
rabbit
and
a
2
generation
reproduction
study
in
rats.
The
toxicology
data
base
was
reviewed
by
the
Hazard
Science
Assessment
Review
Committee
(HIARC)
on
July
7,
1998,
April
7,
1999,
November
2,
1999,
March
1,
2001,
December
18,
2001
and
February
19,
2002.
2.
Determination
of
Susceptibility
There
was
no
evidence
of
quantitative
or
qualitative
susceptibility
following
in
utero
exposures
in
developmental
studies
in
the
rat
and
rabbit.
In
the
reproduction
study,
there
was
evidence
of
quantitative
susceptibility
of
the
offspring.
The
LOAEL
for
parental
systemic
toxicity
was
based
on
decreased
body
weight,
weight
gain,
and
food
consumption;
the
NOAEL
was
27
mg/
kg/
day
in
males
and
30
mg/
kg/
day
in
females.
In
the
offspring
the
LOAEL
was
based
on
increased
numbers
of
F2
pups
with
no
milk
in
the
stomach
and
decreased
pup
survival;
the
NOAEL
was
5
mg/
kg/
day
in
males
and
6
mg/
kg/
day
in
females.
No
adverse
effects
were
observed
in
the
reproductive
parameters;
the
NOAEL
was
the
highest
dose
tested.
In
the
developmental
neurotoxicity
study,
there
was
evidence
of
qualitative
susceptibility.
For
maternal
toxicity,
the
LOAEL
was
based
on
decreased
body
weight
gain,
alterations
in
Functional
Observational
Battery
measurements
and
inhibition
of
plasma,
whole
blood
and
brain
cholinesterase
activity;
the
NOAEL
was
1
mg/
kg/
day.
For
developmental
neurotoxicity,
the
LOAEL
was
based
on
the
morphometric
changes
seen
in
the
brain
of
the
offsprings;
the
NOAEL
was
1
mg/
kg/
day.
3.
Degree
of
Concern
and
Residual
Uncertainties
Since
there
is
evidence
of
increased
susceptibility
of
the
young
following
exposure
to
Carbaryl
in
the
2
generation
reproduction
study
and
in
the
developmental
neurotoxicity
study,
HIARC
performed
a
Degree
of
Concern
Analysis
to:
1)
determine
the
level
of
concern
for
the
effects
observed
when
considered
in
the
context
of
all
available
toxicity
data;
and
2)
identify
any
residual
concerns
after
establishing
toxicity
endpoints
and
traditional
uncertainty
factors
to
be
used
in
the
risk
assessment
of
this
chemical.
If
residual
concerns
are
identified,
HIARC
examines
whether
these
residual
concerns
can
3
be
addressed
by
a
special
FQPA
safety
factor
and,
if
so,
the
size
of
the
factor
needed.
The
results
of
the
HIARC
Degree
of
Concern
analyses
for
Carbaryl
follow.
A.
2
Generation
Reproduction
Study
The
HIARC
concluded
that
there
are
no
residual
concerns
related
to
the
2
generation
reproduction
study
because
the
dose
response
for
the
offspring
effects
is
wellcharacterized
and
these
effects
occurred
at
a
dose
level
which
is
above
that
used
for
establishing
the
Chronic
Reference
Dose
(cRfD)
for
chronic
dietary
risk
assessment.
The
HIARC
established
the
Chronic
RfD
using
the
LOAEL
of
3.1
mg/
kg/
day
in
the
chronic
toxicity
study
in
dogs.
Since
a
NOAEL
was
not
established
in
this
study,
an
additional
uncertainty
factor
of
3X
was
applied
to
the
LOAEL
(i.
e,
UFL).
The
HIARC
determined
that
3X
is
adequate
to
account
for
the
lack
of
a
NOAEL
in
this
case
because:
1)
the
study
was
well
conducted
and
there
are
sufficient
data
from
subchronic
and
other
chronic
studies
in
other
species
that
support
cholinesterase
inhibition
as
the
critical
effect
for
Carbaryl;
2.)
the
data
indicate
that
the
dog
is
more
sensitive
to
the
cholinergic
effects
of
Carbaryl
and
using
this
species
to
establish
the
RfD
provides
additional
protection
for
the
effects
seen
in
the
rat
(including
the
reproduction
and
developmental
neurotoxicity
studies);
3.)
the
magnitude
of
inhibition
of
plasma
cholinesterase
inhibition
(12
23%
decrease)
seen
in
this
study
was
comparable
to
the
magnitude
of
inhibition
(22%)
seen
in
the
5
week
study
in
dogs
indicating
no
cumulative
effect
following
long
term
exposure;
4.)
The
cholinesterase
inhibition
seen
in
females
at
the
LOAEL
in
this
study
was
not
accompanied
by
clinical
signs
(response
was
not
judged
to
be
severe);
and
5.)
no
inhibition
was
seen
for
any
cholinesterase
compartment
in
males
at
this
dose
(response
was
seen
in
only
one
sex).
The
HIARC
concluded
that
the
extrapolated
NOAEL
of
1
mg/
kg/
day
used
to
establish
the
Chronic
RfD
for
Carbaryl
is
below
the
NOAEL
for
offspring
toxicity
(5
mg/
kg/
day)
in
the
2
generation
reproduction
study
and
is
protective
of
chronic
dietary
exposures
to
infants
and
children.
B.
Developmental
Neurotoxicity
Study
The
HIARC
concluded
that
there
was
a
low
level
of
concern
for
the
developmental
effects
seen
in
the
developmental
neurotoxicity
study
and
no
residual
uncertainties
with
respect
to
this
study
based
on
the
following
evidence:
°
Any
concern
for
the
lack
of
brain
morphometric
measurements
in
the
offspring
at
the
mid
dose
(1
mg/
kg/
day)
was
negated
since
even
at
the
high
dose
of
10
mg/
kg/
day,
the
morphometric
changes
were
minimal
and
therefore,
it
is
unlikely
that
adverse
effects
would
be
seen
at
the
mid
dose
level
(1
mg/
kg/
day
10%
of
the
LOAEL).
°
Any
concern
for
the
lack
of
comparative
data
in
adults
and
offspring
for
cholinesterase
inhibition
was
negated
since
no
FOB
alterations
were
seen
in
pups.
4
Other
studies
in
the
data
base
show
that
when
cholinesterase
inhibition
was
seen
in
adult
animals,
it
usually
was
accompanied
by
FOB
alterations.
Additionally,
the
results
of
the
National
Institute
for
Environmental
Health
Sciences
study
(discussed
below)
indicate
that
there
is
no
difference
in
cholinesterase
inhibition
in
pups
and
adults.
The
dose
related
decrease
in
cholinesterase
activity
in
the
brain
and
blood
of
dams
at
gestation
day
19
was
very
similar
to
the
fetal
brain
cholinesterase
levels
taken
at
the
same
time.
The
HIARC
established
the
Acute
RfD
for
Carbaryl
using
the
NOAEL
of
1
mg/
kg/
day
in
the
developmental
neurotoxicity
study
in
rats
which
is
protective
of
single
dose
exposures
to
infants
and
children.
4.
Summary
of
Open
Literature
Findings
In
the
scientific
literature,
there
are
two
relatively
recent
studies
which
demonstrated
effects
on
sperm
at
high
doses
(50
and
100
mg/
kg/
day)
of
Carbaryl.
The
results
of
these
two
studies
indicated
that
Carbaryl
caused
weight
reductions
in
the
testes,
epididymides,
seminal
vesicles,
prostate
and
coagulating
glands
of
young
rats;
changes
in
testicular
enzymes;
decreased
sperm
counts
and
sperm
motility;
increased
sperm
morphological
abnormalities;
and
moderate
atrophy
of
seminiferous
tubules
of
the
testes.
In
a
published
developmental
study
in
Fisher
344
rats
conducted
by
EPA's
Health
Effects
Research
Laboratory,
Carbaryl
was
administered
from
gestation
day
6
through
19
at
doses
of
78
or
104
mg/
kg/
day.
Clinical
signs
related
to
cholinesterase
inhibition
(tremor,
motor
depression,
jaw
clonus
and
lacrimation)
were
observed
in
dams
but
it
is
unclear
if
they
occurred
at
both
dose
levels.
There
was
also
increased
prenatal
mortality
at
the
high
dose
(104
mg/
kg/
day)
and
decreased
pup
weights
at
the
low
(78
mg/
kg/
day)
doses.
In
an
unpublished
developmental
neurotoxicity
study
in
SD
rats
from
the
National
Health
and
Ecological
Effects
Research
Laboratories
at
EPA
and
the
National
Institute
for
Environmental
Health
Sciences/
National
Toxicology
Program
Carbaryl
was
administered
by
gavage
at
doses
of
0,
6,
12
or
25
mg/
kg/
day.
The
chemical
or
its
metabolite
1
naphthol
was
not
present
in
pups'
plasma
above
the
limit
of
detection
at
any
exposure
concentration
(0,
6,
12
or
25
mg/
kg/
day).
There
was
a
dose
related
decrease
in
ChE
activity
in
the
brain
and
blood
of
dams
at
GD
19,
and
fetuses
taken
at
that
time
also
showed
a
very
similar
level
of
inhibition
in
fetal
brain
cholinesterase.
There
was
a
decrease
in
the
number
of
live
pups/
litter
at
the
high
dose.
There
were
no
changes
in
cognitive
function.
Equivocal
changes
in
Functional
Observational
Battery
parameters
were
observed
in
male
and
female
offspring.
II.
EXPOSURE
ASSESSMENT
1.
Dietary
(Food)
Exposure
Considerations
(Correspondence:
V.
Dobozy
to
C.
Christensen
dated
January
7,
2002)
5
Carbaryl
is
used
late
in
the
season
at
maximum
seasonal
rates
of
6
12
lb
of
active
ingredient
(a.
i.)
per
acre.
Pre
harvest
intervals
(PHIs)
range
from
1
29
days,
but
most
PHIs
are
one
week
or
less.
Single
application
rates
are
1
5
lb
ai/
A
with
repeated
applications
on
a
weekly
basis.
U.
S.
tolerances
range
from
10
100
ppm.
Codex
MRLs
have
been
established
for
numerous
commodities,
including
fruits,
grains,
forage/
fodder,
and
livestock
commodities.
The
limits
range
from
0.1/
0.5
for
livestock
commodities
to
100
ppm
for
forage/
hay.
Most
fruit
and
vegetable
limits
range
from
1
to
10
ppm.
Carbaryl
is
registered
for
use
on
almost
all
crop
groups
and
miscellaneous
commodities
including
pome
fruit,
stone
fruit,
legumes,
cereal
grains
and
fruiting
vegetables.
Residues
are
expected
in
meat
and
milk.
The
qualitative
nature
of
the
residue
of
Carbaryl
in
plants
and
animals
is
adequately
understood.
Based
on
the
results
of
plant
and
animal
metabolism
studies,
the
HED
Metabolism
Committee
concluded
that
the
Carbaryl
residue
to
be
regulated
in
plants
is
Carbaryl
per
se
(DP
Barcode
D221979,
S.
Hummel,
2/
8/
96).
The
Metabolism
Committee
also
concluded
that
the
residues
of
concern
in
meat
and
milk
are
the
free
and
conjugated
forms
of
Carbaryl,
5,6
dihydro
5,6
dihydroxy
carbaryl,
and
5
methoxy
6
hydroxy
carbaryl
(C.
Olinger,
D255855,
6/
21/
99).
Residues
are
primarily
surface
residues.
DEEM
analyses
are
being
conducted
at
the
highest
level
of
refinement
available
(Tier
IV).
Adequate
PDP
and
FDA
monitoring
data
are
available
for
the
vast
majority
(>
80%)
of
the
commodities.
These
commodities
include
those
which
are
considered
to
be
significant
in
the
diets
of
children
such
as
apples,
potatoes,
carrots,
succulent
beans,
soybean,
orange,
orange
juice,
apple,
apple
juice,
pear,
peach,
wheat,
banana,
grape,
grape
juice
and
milk.
For
those
commodities
not
monitored
by
FDA
and
PDP,
field
trial
data
will
be
used.
These
include
garden
beets,
turnips,
mustards,
dried
beans,
almonds,
pecans,
walnuts,
field
corn
grain,
rice,
flax
seed,
okra,
olive,
peanuts,
pistachio,
and
sunflower.
Carbaryl
residues
from
field
trials
were
<LOQ
in/
on
sweet
potato,
sugar
beets,
corn
grain,
flax
seed,
and
peanuts.
Quantifiable
residues
were
detected
in
all
other
raw
agricultural
commodities
(RACs).
For
a
given
crop,
residue
levels
were
quite
variable
overall,
probably
owing
to
climactic
variations,
but
were
generally
consistent
within
any
specific
field
trial
location.
Percent
of
crop
treated
will
also
be
incorporated.
Crops
with
the
highest
percent
of
the
crop
treated
include
apples,
(30%),
avocados
(85%),
blueberries(
45%),
cherries
(36%),
asparagus
(87%),
among
others.
Carbamate
market
basket
data
are
also
available
for
the
commodities,
orange,
apple,
peach,
broccoli,
lettuce,
tomato,
bananas,
and
grapes.
Additional
data
were
required
for
the
dermal
use
of
Carbaryl
on
poultry
and
its
use
in
poultry
houses;
however,
the
registrant
has
stated
that
they
are
no
longer
supporting
these
uses.
In
the
previously
conducted
dietary
assessment,
the
current
tolerance
for
poultry
was
used,
and
as
a
result,
poultry
was
determined
to
be
a
significant
contributor
to
the
risk
estimate.
When
poultry
is
not
included
in
the
diet,
the
results
of
the
Critical
6
Exposure
Contribution
analysis
showed
no
specific
commodity
comprised
a
large
percentage
of
the
residues
found
in
the
tail
end
of
acute
exposure.
2.
Dietary
(Drinking
Water)
Exposure
Considerations
(Correspondence:
V.
Dobozy
to
C.
Christensen
dated
January
7,
2002)
The
environmental
fate
data
base
for
Carbaryl
is
adequate
for
the
characterization
of
drinking
water
exposure.
Fate
data
indicate
that
parent
Carbaryl
and
its
degradate
1
naphthol
are
fairly
mobile
and
slightly
persistent.
In
general
they
are
not
likely
to
persist
or
accumulate
in
the
environment,
however,
under
acidic
conditions
with
limited
microbial
activity
they
may
persist.
Because
of
the
relatively
limited
persistence
of
the
compound
in
the
environment
it
is
unlikely
that
non
targeted
monitoring
studies
will
detect
the
maximum
concentrations
that
occur.
Some
non
targeted
monitoring
data
are
available
but
are
of
limited
utility
in
developing
EECs
for
ecological
and
human
health
risk
assessment.
Therefore
modeling
was
used
to
estimate
surface
water
and
groundwater
concentrations
that
could
be
expected
from
normal
agricultural
use.
The
results
of
the
modeling
are
supported
by
the
available
monitoring
data.
For
developing
surface
water,
EECs
computer
modeling
with
the
EPA
PRZM3.12
and
EXAMS
2.97.7
programs
were
used
to
estimate
the
concentration
of
Carbaryl
in
surface
water.
Index
reservoir
scenarios
corrected
for
Percent
Cropped
Area
(PCA)
for
representative
crops
were
used.
SCI
GROW
was
used
to
calculate
a
groundwater
screening
exposure
value
to
be
used
in
determining
the
potential
risk
to
human
health.
3.
Residential
Exposure
Considerations
(Correspondence:
V.
Dobozy
to
C.
Christensen
dated
January
7,
2002)
Carbaryl
is
currently
registered
for
many
residential
uses.
Homeowner
handler
exposure
scenarios
exist
for
a
variety
of
use
patterns
including
applications
of
dusts
to
vegetables,
ornamentals,
and
pets
(dogs
&
cats);
applications
of
ready
to
use
products
for
nuisance
insect
control;
applications
of
liquid
sprays
with
a
variety
of
hand
equipment
to
gardens,
trees,
vegetables,
and
turf;
and
applications
of
granular
formulations
to
turf.
Carbaryl
can
be
used
in
outdoor
residential
areas
and
to
treat
pets.
Therefore,
a
number
of
residential
post
application
exposure
scenarios
exist
for
toddlers
and
children.
Several
chemical
and
scenario
specific
studies
designed
to
quantify
exposures
to
homeowner
applicators
are
available.
There
are
a
number
of
dislodgeable
foliar
residue
studies
for
Carbaryl
that
have
been
used
for
home
gardening
activities.
Also,
there
are
TTR
data
from
3
sites
(CA,
PA,
GA)
that
have
been
used
for
the
dermal
risk
assessments
(i.
e.,
transferability
is
>1%).
Mouthing
behaviors
have
been
addressed
using
the
new
5%
factor
for
wet
hands
and
not
the
TTRs
as
stipulated
in
the
latest
updates
to
the
Residential
SOPs.
These
data
will
be
used,
where
appropriate,
to
calculate
residue
concentrations
7
and
exposures
over
time
instead
of
using
the
Agency
default
assumptions.
In
addition,
the
latest
Outdoor
Residential
Exposure
Task
Force
(ORETF)
data
for
homeowner
applications
to
turf
have
been
used
which
are
also
the
same
values
that
have
been
incorporated
in
the
Residential
SOPs.
For
any
other
remaining
scenarios
not
addressed
by
the
Aventis
or
ORETF
data,
PHED
or
the
Residential
SOPs
were
used.
III.
SAFETY
FACTOR
RECOMMENDATION
AND
RATIONALE
1.
FQPA
Safety
Factor
Recommendations
The
FQPA
SFC
recommends
that
OPP
depart
from
the
default
10X
additional
safety
factor
and
instead
use
a
different
additional
safety
factor
of
3X.
This
recommendation
is
based
on
reliable
data
supporting
the
findings
set
forth
below.
A.
Traditional
Additional
Safety
Factor
(Addressing
Data
Deficiencies)
The
FQPA
SFC
concurs
with
the
HIARC
recommendation
for
the
use
of
a
3X
additional
safety
factor
to
address
the
use
of
a
LOAEL
in
establishing
the
Acute
and
Chronic
RfDs,
and
the
toxicity
endpoints
selected
to
assess
short
and
long
term
residential
exposure
scenarios
(oral,
dermal,
and
inhalation).
The
rationale
as
to
why
reliable
data
support
the
safety
of
using
a
3X
to
address
this
data
deficiency
is
discussed
above
in
Section
I.
3.
B.
Special
FQPA
Safety
Factors
Taking
into
account
the
HIARC
recommendation
regarding
the
data
deficiency,
the
FQPA
SFC
recommends
that
no
Special
FQPA
Safety
Factor
is
necessary
to
protect
the
safety
of
infants
and
children
in
assessing
Carbaryl
exposure
and
risks.
2.
Rationale
and
Findings
Regarding
Recommendation
on
Special
FQPA
Safety
Factor
The
Committee
concluded
that
no
Special
FQPA
safety
factor
was
needed
because:
The
toxicology
database
is
complete
and
there
is
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
in
rat
or
rabbit
fetuses
following
in
utero
in
the
standard
developmental
studies.
Although
there
is
evidence
of
qualitative
susceptibility
developmental
neurotoxicity
study,
HIARC
concluded
there
is
a
low
level
of
concern
for
the
effects
in
the
developmental
neurotoxicity
study,
as
discussed
in
Section
I.
3.
The
RfDs
established
would
account
for
any
uncertainties
and
are
protective
of
prepre
postnatal
toxicity
following
acute
and
chronic
exposures.
Similarly,
although
there
is
evidence
of
increased
susceptibility
in
the
offspring
in
the
2
generation
reproduction
study,
there
are
no
residual
uncertainties
(Refer
to
Section
I.
3.).
The
chronic
RfD
would
be
protective
of
the
pre
pre/
post
natal
toxicity
following
chronic
dietary
exposures.
The
8
doses/
endpoints
selected
for
residential
exposures,
are
also
protective
of
any
pre
pre/
post
natal
toxicity
resulting
from
non
dietary
exposures.
There
are
no
residual
uncertainties
identified
in
the
exposure
databases.
The
dietary
food
exposure
assessment
utilizes
estimates
derived
from
monitoring
data
(PDP,
FDA),
the
carbamate
market
basket
survey,
percent
crop
treated
information
(as
applicable),
and
processing
data.
The
dietary
drinking
water
assessment
includes
a
complete
environmental
fate
database
for
both
the
parent
and
the
major
metabolite
(1
napthol)
and
uses
modeling
results
based
on
detailed
chemical
specific
data.
The
modeling
results
are
supported
by
drinking
water
monitoring
data
and
do
not
underestimate
the
exposure
and
risks
posed
by
Carbaryl.
The
residential
exposure
assessment
includes
chemical
specific
dislodgeable
foliar
residue
studies
(DFRs),
ORETF
data,
a
registrant
submitted
use
and
usage
study,
and
chemical
specific
total
transferable
residue
(TTR)
studies
for
the
handler
and
post
application
scenarios.
In
addition,
there
are
human
biomonitoring
data
to
support
the
results
of
the
residential
exposure
estimate.
3.
Application
of
the
FQPA
Safety
Factors
(Population
Subgroups
/
Risk
Assessment
Scenarios)
The
FQPA
safety
factor
recommendation
is
for
a
3X
traditional
safety
factor
to
address
data
deficiencies
and
no
additional
Special
FQPA
safety
factor.
The
3X
traditional
safety
factor
should
be
applied
to
the
Chronic
RfD
and
to
long
term
residential
exposure
scenarios
(dermal,
and
inhalation).
No
other
FQPA
safety
factor
would
be
appropriate
for
Carbaryl.
9
4.
Summary
of
FQPA
Safety
Factors
Summary
of
FQPA
Safety
Factors
for
Carbaryl
LOAEL
to
NOAEL
(UFL)
Subchronic
to
Chronic
(UFS)
Incomplete
Database
(UFDB)
Special
FQPA
Safety
Factor
(Hazard
and
Exposure)
Magnitude
of
Factor
3X
1X
1X
1X
Rationale
for
the
Factor
Use
of
a
LOAEL
to
establish
toxicity
endpoint
(i.
e,
a
NOAEL
was
not
identified
in
the
critical
study).
Refer
to
Section
I.
3.
No
subchronic
to
Chronic
extrapolations
performed
Toxicity
Database
is
complete
No
residual
concerns
regarding
pre
or
post
natal
toxicity
or
completeness
of
the
toxicity
or
exposure
databases
Endpoints
to
which
the
Factor
is
Applied
Chronic
dietary
and
Long
term
residential
exposures
(Dermal
and
Inhalation)
Not
Applicable
Not
Applicable
Not
Applicable
| epa | 2024-06-07T20:31:42.345411 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0010/content.txt"
} |
EPA-HQ-OPP-2002-0138-0012 | Supporting & Related Material | "2002-08-27T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES,
AND
TOXIC
SUBSTANCES
DP
Barcode:
D276945
PCCode:
056801
Date:
August
17,
2002
MEMORANDUM:
SUBJECT:
Revised
EFED
Risk
Assessment
of
Carbaryl
in
Support
of
the
Reregistration
Eligibility
Decision
(RED)
To:
Anthony
Britten,
PM
Team
Reviewer
Betty
Shackleford,
Product
Manager
53
Special
Review
and
Reregistration
Division
(7508C)
FROM:
E.
Laurence
Libelo,
Ph.
D.,
Environmental
Engineer
Thomas
Steeger,
Ph.
D.,
Senior
Biologist
Environmental
Risk
Branch
IV
Environmental
Fate
and
Effects
Division
(7507C)
THRU:
Betsy
Behl,
Chief
Environmental
Risk
Branch
IV/
Environmental
Fate
and
Effects
Division
(7507C)
The
Environmental
Fate
and
Effects
Division
has
revised
the
Environmental
Fate
and
Ecological
Risk
Assessment
chapter
in
support
of
the
reregistration
eligibility
decision
on
carbaryl.
The
chapter
has
been
abridged
from
its
April
8,
2002,
version
at
the
request
of
the
Special
Review
and
Reregistration
Division
and
no
longer
includes
environmental
fate
data
evaluation
records
contained
in
the
original
chapter.
Although
the
data
evaluation
records
were
cleared
for
confidential
business
information,
their
presence
in
the
chapter
did
not
contribute
significantly
to
understanding
the
environmental
fate
of
carbaryl.
If
interested,
the
public
can
access
both
environmental
fate
and
ecological
effect
data
evaluation
records
by
petitioning
the
Agency
through
the
Freedom
of
Information
Act.
The
revised
chapter
reflects
comments
made
by
the
registrant
(Aventis)
during
the
30
day
error
correction
phase
of
the
review
process
and
contains
more
detailed
information
on
the
input
files
for
the
Pesticide
Root
Zone
Model
(PRZM)
used
in
estimating
runoff
concentrations
of
carbaryl.
Although
the
registrant
provided
constructive
comments
in
their
30
day
responses
to
the
draft
risk
assessment
of
carbaryl,
the
overall
concerns
and
uncertainties
originally
identified
regarding
the
environmental
fate
and
ecological
effects
of
carbaryl
have
not
changed.
Also
included
with
the
revised
chapter
is
a
review
(DP
Barcode
D279109)
of
data
submitted
regarding
the
Section
24C
Special
Local
Needs
use
of
carbaryl
on
oyster
beds
in
Willapa
Bay
and
Grays
Harbor,
Washington,
for
control
of
burrowing
shrimp.
Both
the
revised
environmental
fate
and
ecological
effects
chapter
and
the
review
of
the
use
of
carbaryl
to
control
burrowing
shrimp
are
intended
to
represent
EFED's
assessment
of
the
risks
associated
with
the
uses
of
carbaryl.
While
some
uses
and
application
rates
discussed
in
the
chapter
may
no
longer
be
supported,
the
EFED
chapter
is
intended
to
provide
a
general
overview
of
the
concerns
and
uncertainties
associated
with
the
past
and
present
uses
of
carbaryl.
Environmental
Fate
and
Ecological
Risk
Assessment
For
the
Reregistration
of
Carbaryl
1
Naphthyl
methylcarbamate
1
naphthyl
N
methylcarbamine
CAS
Registry
Number
63
25
2
PC
Code
056801
Prepared
by:
E.
Laurence
Libelo,
Ph.
D.,
Environmental
Engineer
Angel
Chiri,
Ph.
D.,
Entomologist
Thomas
M.
Steeger,
Ph.
D.,
Fishery
Biologist
United
States
Environmental
Protection
Agency
Office
of
Pesticide
Programs
Environmental
Fate
and
Effects
Division
Environmental
Risk
Branch
IV
Ariel
Rios
Building
1200
Pennsylvania
Ave.,
N.
W.
Mail
Code
7507C
Washington,
DC
20460
Reviewed
by:
Elizabeth
Behl,
Branch
Chief
Dana
Spatz,
Senior
Chemist
i
TABLE
OF
CONTENTS
1.0
Summary
and
Environmental
Risk
Conclusions
.............................
1
Risk
to
Terrestrial
Organisms
..............................................
1
Risk
to
Plants
...........................................................
3
Risk
to
Endangered
Species................................................
3
Fate
and
Water
Assessment
................................................
4
2.0
Introduction
...........................................................
7
3.0
Integrated
Risk
Characterization
..........................................
8
Introduction
............................................................
8
Aquatic
Organisms
.......................................................
9
Terrestrial
Organisms
...................................................
12
Endangered
Species
.....................................................
15
Endocrine
Disruption
Concerns
............................................
15
Uncertainties
..........................................................
16
4.0
Environmental
Fate
Assessment
..........................................
17
Exposure
Characterization
................................................
17
Persistence
......................................................
21
Chemical
Degradation
Processes...............................
21
Hydrolysis
..........................................
21
Photolysis.................................................
21
Microbially
mediated
Processes
...............................
21
Mobility
........................................................
22
Batch
Adsorption/
Desorption
.................................
22
Column
Leaching
...........................................
23
Field
Dissipation
.................................................
23
Terrestrial
Field
Dissipation
..................................
23
Forestry
Field
Dissipation
....................................
24
Aquatic
Field
Dissipation
....................................
24
Bioaccumulation
in
Fish
...........................................
24
Foliar
Dissipation.................................................
25
Atmospheric
Transport
............................................
25
1
Naphthol
Fate
and
Transport
......................................
26
Aquatic
Exposure
Assessment
.............................................
27
Urban
and
Suburban
....................................................
29
Estimated
Environmental
Concentrations
for
Terrestrial
Ecological
Risk
Assessment................................................
29
5.0
Drinking
Water
Assessment
.............................................
30
Water
Resources
Assessment
.............................................
30
ii
Drinking
Water
Exposure
Assessment
................................
31
Drinking
Water
Modeling
....................................
31
Water
Treatment
Effects
.........................................................
32
Groundwater
Resources
............................................
33
Surface
Water
Resources
...........................................
34
Monitoring
Data............................................
34
NAWQA
...........................................
34
Registrant
Monitoring
Study
............................
35
Sacramento
San
Joaquin
River
Delta
.....................
37
STORET
...........................................
37
6.0
Hazard
and
Risk
Assessment
for
Aquatic
Organisms
........................
37
Hazard
Assessment
for
Aquatic
Organisms
..................................
37
Freshwater
Fish
..................................................
37
Amphibians
.....................................................
38
Freshwater
Invertebrates
...........................................
38
Estuarine/
Marine
Fish
.............................................
39
Estuarine/
Marine
Invertebrates
......................................
39
Aquatic
Plants
...................................................
40
1
Naphthol
......................................................
40
Risk
Assessment
for
Aquatic
Organisms.....................................
40
Freshwater
Fish
..................................................
40
Freshwater
Aquatic
Invertebrates
....................................
41
Estuarine/
Marine
Fish
.............................................
41
Estuarine/
Marine
Invertebrates
......................................
44
Reproduction
Effects
on
Fish
.......................................
44
Endangered
Aquatic
Species
.............................................
45
7.0
Hazard
and
Risk
Assessment
for
Terrestrial
Organisms
.....................
45
Hazard
Assessment
for
Terrestrial
Organisms
................................
45
Avian
..........................................................
45
Mammalian
.....................................................
46
Insects
.........................................................
46
Terrestrial
Plants
.................................................
46
Risk
Assessment
for
Terrestrial
Organisms...................................
47
Avian
Risk
......................................................
47
Nongranular
Formulations
....................................
47
Granular
Formulations.......................................
48
Mammalian
Risk
.................................................
48
Risk
to
Herbivores/
Insectivores:
Nongranular
Formulations
.........
48
Risk
Quotients
for
Herbivores/
Insectivores
Based
on
Less
than
Maximum
Label
Use
Rates
.......................
48
iii
Risk
Quotients
for
Herbivores/
Insectivores
Based
on
Maximum
Label
Use
Rates
...............................
48
Risk
to
Granivores:
Nongranular
Uses
..........................
49
Chronic
Risk:
Nongranular
Uses
.........................
50
Risk:
Granular
Uses...................................
50
Reproduction
Effects
.............................................
50
Insects
.........................................................
51
Terrestrial
Plants
.................................................
52
Endangered
Terrestrial
Species
......................................
52
8.0
Summary
of
Ecological
Incident
Data
....................................
53
9.0
References
(Non
MRID)
................................................
55
Appendix
A:
Refined
Water
Memo
.............................................
62
Appendix
B:
Ecological
Risk
Assessment
.......................................
147
Appendix
C:
Toxicity
Assessment
.............................................
172
Appendix
D:
ELL
FATE
.....................................................
183
Appendix
E:
Examples
of
PRZM
Standard
Pond
Input
Files
.......................
185
1
1.0
Summary
and
Environmental
Risk
Conclusions
Carbaryl
is
a
carbamate
insecticide
registered
for
control
of
a
wide
range
of
insect
and
other
arthropod
pests
on
over
100
crop
and
noncrop
use
sites,
including
home
and
garden
uses.
Carbaryl
is
a
cholinesterase
inhibitor
that
acts
on
animals
on
contact
and
upon
ingestion
by
competing
for
binding
sites
on
the
enzyme
acetyl
cholinesterase,
thus
preventing
the
breakdown
of
acetyl
choline.
Risk
to
Terrestrial
Organisms
°
Three
different
kinds
of
usage
data
were
considered
to
assess
risk
to
terrestrial
organisms:
maximum
label
rates
for
74
uses,
maximum
reported
(based
on
survey
usage
data
available
from
the
Doane's
Agricultural
Services
for
42
uses)
rates,
and
Quantitative
Usage
Analysis
"average"
rates
data
provided
by
OPP's
Biological
and
Economic
Analysis
Division
for
70
uses.
In
most
cases
the
Level
of
Concern
(LOC)
exceedance
pattern
was
not
significantly
affected
by
the
kind
of
application
rate
data
used
to
calculate
risk
quotients.
°
Although
no
avian
acute
risk
LOCs
are
exceeded
for
any
nongranular
carbaryl
uses
at
maximum
or
less
than
maximum
label
application
rates,
the
avian
chronic
risk
LOC
is
exceeded
for
most
uses.
The
avian
acute
LOC
is
exceeded
for
20
g
birds
for
all
granular
carbaryl
uses
(risk
quotients
[RQs]:
0.52
4.76)
and
for
180
g
birds,
it
is
exceeded
for
the
trees/
ornamentals,
turfgrass,
and
tick
control
uses
(RQ:
0.53).
No
acute
LOCs
are
exceeded
for
birds
in
the
1000
g
weight
class
for
any
of
the
granular
carbaryl
uses.
°
At
maximum
label
rates,
the
mammalian
acute
risk
LOC
(0.5)
is
exceeded
for
all
74
nongranular
uses
(0.76
12.12).
The
proportion
of
RQs
exceeding
the
acute
LOCs
decreases
significantly
for
mammals
in
all
three
weight
classes
feeding
on
fruits,
pods,
seeds,
and
large
insects,
as
well
as
for
the
1000
g
mammals
feeding
on
broadleaf/
forage
plants
and
small
insects.
At
maximum
reported
application
rates
the
acute
risk
LOC
for
15
g
mammals
feeding
on
short
grass
is
exceeded
for
41
of
42
nongranular
carbaryl
uses
(RQs:
0.60
11.36
and
at
"average"
use
rates
is
exceeded
for
63
of
70
uses.
°
The
mammalian
chronic
risk
LOC
(1)
is
exceeded
for
practically
all
nongranular
carbaryl
uses
at
maximum
label
(RQs:
3.0
48.0),
maximum
reported
(RQs:
1.5
45.0),
and
"average"
use
rates
(RQs:
1.5
15.9).
Therefore,
almost
all
nongranular
carbaryl
uses
are
expected
to
pose
acute
and
chronic
risks
to
small
mammals.
°
At
maximum
label
rates,
acute
risk
LOCs
are
exceeded
for
15
g
mammals
(RQs:
2.3
21.1)
and
35
g
mammals
(RQs:
0.99
9.04)
for
all
granular
uses,
indicating
that
all
granular
carbaryl
uses
pose
an
acute
risk
to
the
smaller
mammalian
species.
For
1000
g
mammals,
the
acute
risk
LOC
is
not
exceeded
for
any
use.
°
Being
highly
toxic
to
honey
bees
and
arthropods
in
general,
carbaryl
poses
a
risk
to
beneficial
insects,
including
many
pests's
natural
enemies,
when
directly
exposed
to
carbaryl
applications,
residues
on
foliage,
or
contaminated
pollen
or
nectar.
Carbaryl
is
one
of
the
2
pesticides
more
often
implicated
in
bee
mortality
incidents,
ranking
second
and
third,
respectively,
in
two
separate
bee
kill
surveys
undertaken
in
1997
by
the
Washington
State
Department
of
Agriculture
and
the
American
Beekeeping
Federation.
Risk
to
Aquatic
Organisms
°
Three
different
application
scenarios
were
considered
in
assessing
risk
to
aquatic
organisms:
maximum
label
rates,
maximum
reported
(based
on
survey
usage
data
available
for
42
uses)
rates,
and
"average"
rates.
In
most
cases
the
Level
of
Concern
(LOC)
exceedance
pattern
was
unaffected
by
the
kind
of
usage
data
used
to
calculate
risk
quotients.
°
The
acute
risk
LOC
(0.5)
for
freshwater
fish
is
exceeded
for
one
of
five
use
scenarios
modeled
(citrus),
at
maximum
label
(RQ:
1.10),
maximum
reported
(RQ:
0.93),
and
"average"
(RQ:
0.58)
use
rates,
while
the
chronic
risk
LOC
for
freshwater
fish
is
not
exceeded
for
any
scenario,
at
any
use
rate.
°
The
acute
risk
LOC
for
estuarine/
marine
fish
is
not
exceeded
for
any
use
scenario
modeled,
at
any
use
rate.
Because
of
lack
of
valid
chronic
toxicity
data,
it
is
not
possible
to
fully
assess
chronic
risk
to
estuarine/
marine
fish
at
this
time.
°
Available
nonguideline
studies
suggest
that
exposure
to
carbaryl
may
act
as
a
potential
endocrine
disruptor
in
fish.
Exposure
to
sublethal
carbaryl
levels
cause
a
significant
reduction
of
serum
and
pituitary
levels
of
gonadotropic
hormone
and
gonadotropin
releasing
hormone
in
the
freshwater
murrell
and
a
significant
decline
in
ovarian
estrogen
levels
in
freshwater
perch,
starting
on
day
15
of
exposure.
°
Most
carbaryl
uses
are
likely
to
pose
an
acute
risk
to
both
freshwater
and
estuarine/
marine
aquatic
invertebrates,
especially
arthropods.
The
acute
risk
LOC
(0.5)
for
freshwater
invertebrates
is
exceeded
for
all
five
use
scenarios
modeled
at
maximum
label
(RQs:
5.1
161.2
maximum
reported
(RQs:
3.3
136.5),
and
"average"
(RQs:
2.6
85.3)
use
rates.
The
chronic
risk
LOC
(1)
is
also
exceeded
for
freshwater
invertebrates
for
all
5
use
scenarios
modeled,
at
maximum
label
(RQs:
3.3
91.3),
maximum
reported
(RQs:
2.0
74.7),
and
"average"
(RQs:
1.7
44.7)
use
rates.
°
The
acute
risk
LOC
is
exceeded
for
estuarine/
marine
invertebrates
for
the
5
use
scenarios
modeled
at
maximum
label
(RQs:
1.5
48.1),
maximum
reported
(RQs:
1.0
40.7),
and
"average"
(RQs:
0.8
25.4)
use
rates.
Lack
of
reliable
toxicity
data
precluded
the
assessment
of
chronic
risk
for
estuarine/
marine
invertebrates.
°
Carbaryl
directly
applied
to
oyster
beds
in
Washington
State
poses
a
severe,
albeit
localized
and
temporary,
acute
risk
to
fish
and
nontarget
arthropods
in
and
around
the
target
area.
The
oyster
industry
is
encouraged
to
continue
searching
for
alternative
pest
shrimp
management
measures
and
more
selective
carbaryl
application
regimes,
within
an
IPM
context,
to
minimize
impact
on
non
target
organisms.
3
Risk
to
Plants
°
Carbaryl
can
be
used
as
a
fruit
thinning
agent
on
apples
and
pears,
and
according
to
the
label
it
may
cause
injury
to
tender
foliage
if
applied
to
wet
foliage
or
during
periods
of
high
humidity.
It
may
also
cause
injury
to
Boston
ivy,
Virginia
creeper,
or
maidenhair
fern.
A
few
incidents
involving
injury
to
vegetable
crops
(potatoes,
tomatoes,
cabbage,
and
broccoli)
have
been
reported.
To
fully
assess
carbaryl
risk
to
terrestrial
plants,
Tier
I
and,
if
appropriate,
Tier
II
Seed
Germination
and
Seedling
Emergence,
as
well
as
Vegetative
Vigor
studies
should
be
submitted
by
the
registrant.
°
Based
on
the
single
core
green
alga
study
available,
the
acute
risk
LOC
for
aquatic
plants
is
not
exceeded
for
any
of
the
five
scenarios
modeled
even
at
maximum
label
rates.
However,
because
four
of
the
required
five
toxicity
studies
with
aquatic
plants
are
unavailable,
these
results
are
insufficient
to
fully
assess
carbaryl
risk
to
aquatic
plants.
Toxicity
testing
for
aquatic
plants
is
required
to
support
carbaryl's
registered
forestry
uses.
Risk
to
Endangered
Species
°
The
endangered
species
LOC
for
birds
is
met
or
exceeded
for
most
nongranular
carbaryl
uses
at
maximum
label,
QUA
average,
and
maximum
reported
use
rates.
The
endangered
species
LOC
is
exceeded
for
20
g
birds
for
all
granular
uses;
it
is
exceeded
for
180
g
birds
it
is
exceeded
for
all
granular
uses,
except
cucumber,
melons,
pumpkin,
squash,
beans,
peas,
lentils,
cowpeas,
southern
peas,
wheat,
millet,
and
sugar
beets;
and
for
1000
g
birds,
it
is
reached
for
the
trees
and
ornamentals,
turfgrass,
and
tick
control
granular
uses.
°
The
endangered
species
LOC
for
mammals
is
met
or
exceeded
for
all
uses
at
maximum
label,
QUA
average,
and
maximum
reported
use
rates.
°
At
less
than
maximum
label
rates
the
endangered
species
LOC
is
exceeded
for
all
carbaryl
uses
for
freshwater
and
marine/
estuarine
aquatic
invertebrates.
At
less
than
maximum
label
rates,
the
endangered
species
LOC
is
exceeded
for
freshwater
fish
only
for
the
citrus
use
scenario
and
not
exceeded
for
estuarine/
marine
fish
for
any
of
the
five
use
scenarios
modeled.
4
Fate
and
Water
Assessment
°
Carbaryl
is
widely
detected
in
surface
water
at
concentrations
up
to
about
7
:
g/
L.
In
general
observed
concentrations
are
generally
less
then
0.5
:
g/
L.
It
was
the
second
most
widely
detected
insecticide,
after
diazinon,
in
the
U.
S.
Geological
Survey's
National
Water
Quality
Assessment
(NAWQA)
program.
NAWQA
reported
that
about
20
%
of
surface
water
samples
had
detectable
carbaryl
concentrations.
For
samples
where
carbaryl
was
detected
the
mean
concentration
was
0.11
:
g/
L
and
the
maximum
was
5.5
:
g/
L.
Urban
streams
had
higher
frequency
of
detection
then
those
draining
agricultural
areas,
and
had
higher
concentrations.
A
targeted
study
by
the
registrant
found
detectable
levels
of
carbaryl
in
9
of
15
sites
in
agricultural
areas
and
100%
of
4
sites
in
suburban
areas
(limit
of
detection
=
0.002
:
g/
L).
Raw
water
samples
from
suburban
sites
had
measured
residues
greater
then
the
limit
of
detection
but
below
the
level
of
quantitation
(0.03
:
g/
L)
ranging
from
0.002
to
0.023
:
g/
L.
Concentrations
in
samples
from
agricultural
sites
were
lower,
with
one
sample
measuring
about
0.16
:
g/
L,
one
at
0.031
:
g/
L
and
the
rest
were
below
the
level
of
quantitation.
While
this
study
was
targeted
at
carbaryl
use
areas
only
20
sites
were
sampled.
It
is
not
known
how
the
selected
sites
relate
to
the
overall
distribution
of
possible
exposures.
The
concentrations
found
in
this
study
are
similar
to
those
reported
n
non
targeted
studies.
They
are
not
the
maximum
that
occur
as
evidenced
by
higher
values
found
in
non
targeted
studies.
°
Because
of
the
relatively
limited
persistence
of
the
compound
in
the
environment
it
is
unlikely
that
non
targeted
monitoring
studies
will
detect
the
maximum
concentrations
that
occur.
Extensive
data
from
targeted
studies
designed
specifically
to
measure
carbaryl
in
relation
to
actual
application
and
environmental
occurrence
is
not
available.
Only
the
registrant
study
has
tried
to
target
use
areas.
This
study,
while
useful,
is
limited
in
extent
and
did
not
measure
the
concentrations
as
high
as
observed
in
other,
non
targeted
studies.
Because
of
the
limited
number
of
sites
sampled
and
lack
of
information
on
how
sampled
sites
relate
to
the
overall
carbaryl
use
area
this
study
can
not
be
used
to
estimate
the
distribution
of
expected
environmental
concentrations
which
actually
occur.
Targeted
monitoring
data
is
limited
to
this
study
which
found
concentrations
below
those
observed
in
other
studies.
This
lack
of
extensive
targeted
data
and
the
limitations
inherent
in
using
non
targeted
data
to
extrapolate
to
actual
environmental
concentrations
indicate
that
computer
modeling
may
provided
a
more
representative
estimate
of
actual
peak
concentrations
that
occur.
°
Computer
modeling
using
the
EPA
PRZM3.12
and
EXAMS
2.97.5
programs
were
used
to
estimate
the
maximum
and
average
concentrations
of
carbaryl
in
surface
water.
Estimated
environmental
concentrations
(EECs)
for
use
in
human
health
risk
assessment
were
developed
by
modeling
with
Index
Reservoir
scenarios
corrected
for
Percent
Cropped
Area
(PCA)
for
representative
crops.
Three
different
application
rate
scenarios
were
used
in
modeling:
the
maximum
allowed
on
the
label
for
the
specific
crop,
an
"average"
rate,
and
1
Maximum
is
the
highest
application
rate
allowed
according
to
the
label
for
the
specific
crop.
"Average"
is
the
average
rate
as
determined
by
OPP/
BEAD
and
reported
in
the
a
memo
titled
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD.
These
average
rates
are
presented
here,
but
are
not
relevant
for
drinking
water
exposure
estimates
as
the
usage
is
averaged
over
a
geographic
area.
The
values
do
not
represent
a
typical
rate
that
a
user
in
a
specific
area
applies.
Maximum
used
is
the
highest
rate
of
application
that
is
actually
reported
to
be
used
based
on
OPP/
BEAD
analysis
of
DoaneS
survey
data.
5
the
maximum
rate
reported
to
actually
be
used
1
.
EECs
varied
greatly
depending
on
the
geographic
location,
crop
and
application
rate.
EEC
values
ranged
from
about
10
:
g/
L
from
sugar
beets
to
about
500
:
g/
L
from
citrus.
Chronic
EECs
ranged
from
about
1
to
28
:
g/
L.
With
the
exception
of
Florida
citrus
the
calculated
EECs
are
3
5
times
as
high
as
concentrations
observed
in
monitoring
data.
It
is
highly
unlikely
that
any
but
the
most
extensive
targeted
monitoring
would
capture
the
actual
peak
concentrations,
and
the
results
of
the
modeling
provide
an
conservative,
though
not
unreasonable,
estimate
of
possible
concentrations
in
drinking
water.
°
The
maximum
calculated
EEC
resulted
from
use
on
citrus
in
Florida.
A
more
detailed
assessment
of
the
source
of
water
used
to
provide
drinking
water
and
the
relationship
between
the
areas
where
carbaryl
is
used
and
surface
water
supply
sources
is
required
to
more
accurately
evaluate
possible
human
exposures.
In
1995,
seven
percent
of
Florida's
population
(about
one
million
people)
relied
on
surface
water
for
their
drinking
water
needs
(Marella,
1999).
A
subset
of
these
people
get
their
water
from
citrus
areas.
Until
more
accurate
data
on
land
use
and
related
pesticide
application
is
available
and
can
be
linked
with
data
on
the
location
and
hydraulic
characteristics
of
the
water
bodies
used
for
water
supply
it
is
not
possible
to
provide
a
more
accurate
assessment
of
possible
exposures.
Also,
the
Percent
Crop
Area
for
citrus
may
be
much
lower
then
the
default
minor
use
crop
value
of
87%
so
the
corresponding
concentration
may
be
lower.
°
Carbaryl
and
its
degradate
1
naphthol
are
fairly
mobile
and
slightly
persistent.
In
general
they
are
not
likely
to
persist
or
accumulate
in
the
environment.
Under
acidic
conditions
with
limited
microbial
activity
they
may
persist.
°
Carbaryl
dissipates
in
the
environment
by
abiotic
and
microbially
mediated
degradation.
The
major
degradation
products
are
CO2
and
1
naphthol,
which
is
further
degrade
to
CO2.
Carbaryl
is
stable
to
hydrolysis
in
acidic
conditions,
but
hydrolyzes
in
neutral
(half
life
=
12
days)
and
alkaline
environments
(pH
9
half
life
=
3.2
hours).
Carbaryl
is
degraded
by
abiotic
photolysis
in
water
with
a
half
life
of
21
days.
Under
aerobic
conditions
the
compound
degrades
rapidly
by
microbial
metabolism,
with
half
lives
of
4
to
5
days
in
soil
and
aquatic
environments.
In
anaerobic
environments
metabolism
is
much
slower
with
halflives
on
the
order
of
2
to3
months.
Carbaryl
is
considered
to
be
moderately
mobile
in
the
environment
(Kf
=1.7
to
3.5).
°
The
major
metabolite
of
carbaryl
degradation
by
abiotic
and
microbially
mediated
processes
is
1
naphthol.
This
degradate
represented
up
to
67%
of
the
applied
carbaryl
in
degradation
6
studies.
It
is
also
formed
in
the
environment
by
degradation
of
naphthalene
and
other
polyaeromatic
hydrocarbon
compounds.
Only
limited
information
is
available
for
the
environmental
transport
and
fate
1
naphthol.
While
guideline
studies
were
not
submitted
specifically
for
the
degradate,
open
literature
information
suggests
that
it
is
less
persistent
and
less
mobile
than
parent
carbaryl.
°
Monitoring
data
for
carbaryl
in
groundwater
suggest
that
carbaryl
is
not
a
major
groundwater
contaminant
though
targeted
data
is
not
available.
Parent
carbaryl
is
detected
in
about
1
%
of
well
samples
in
non
targeted
monitoring
studies,
generally
at
low
concentrations
(<
0.1
:
g/
L).
In
the
U.
S.
G.
S
NAWQA
program
detections
in
groundwater
were
mainly
from
three
setting:
wheat
(5.8
%
of
well
samples
from
wheat
land
use
),
orchards
and
vineyards
(1.7
%
of
well
samples
from
orchard
and
vineyard
land
use),
and
urban
(1.8%
of
urban
groundwater
samples).
2
Quantitative
Usage
Analysis
for
Carbaryl,
OPP/
BEAD,
1998
7
2.0
Introduction
Carbaryl
(1
naphthyl
N
methylcarbamate)
is
a
broad
spectrum
carbamate
insecticide
and
acaricide
registered
for
control
of
over
300
species
of
insects
and
mites
on
over
100
crop
and
noncrop
use
sites,
including
homeowner
uses;
pet,
and
poultry
uses;
and
treatment
of
oyster
beds.
As
other
carbamates,
carbaryl
is
a
cholinesterase
inhibitor
that
acts
on
animals
on
contact
and
upon
ingestion
by
inactivating
the
enzyme
acetylcholinesterase
and
blocking
the
degradation
of
the
neurotransmitter
acetylcholine.
As
a
result,
the
build
up
of
acetylcholine
causes
an
over
stimulation
of
the
central
nervous
system.
Introduced
in
1956,
carbaryl
was
the
first
carbamate
insecticide
to
be
successfully
marketed
for
a
wide
range
of
agricultural
and
household
lawn
and
garden
uses.
Approximately
2.5
million
pounds
of
carbaryl
are
applied
annually
in
the
U.
S.
A
map
showing
the
widespread
use
of
carbaryl
in
agriculture
is
shown
in
Figure
1.
Technical
carbaryl
is
a
white
crystalline
solid
that
has
no
appreciable
odor.
Carbaryl
end
use
formulations
include
aqueous
dispersions,
baits
dusts,
emulsifiable
concentrates,
flowables,
granules,
oil
based
flowables,
powder,
soluble
concentrates,
suspension
concentrates,
wettable
powders,
water
based
flowables,
water
dispersible
granules,
and
ready
to
use
formulations.
Carbaryl
can
be
applied
by
aircraft,
ground
equipment,
and
sprinkler
irrigation.
The
principal
registrant
is
Aventis.
For
the
years
of
1987
96,
carbaryl
usage
averaged
approximately
2.5
million
pounds
a.
i.
for
over
1.5
million
acres
treated.
Average
estimates
for
major
crops
treated
include
alfalfa
(120,000
acres),
apples
(131,000
acres),
corn
(82,000
acres),
hay
(91,000
acres),
pecans
(95,000
acres),
soybeans
(101,000
acres),
and
wheat
(106,000
acres).
Crops
with
a
high
percentage
of
the
total
planted
acreage
treated
include
Chinese
cabbages
(57%),
asparagus
(43%),
cranberries
(39%),
Brussels
sprouts
(33%),
okra
(32%),
pumpkins
(31%),
and
sweet
cherries
(25%)
2
.
Carbaryl
is
also
used
for
residential
and
other
non
agricultural
uses,
being
the
seventh
most
commonly
used
insecticide
around
the
home.
8
Figure
1:
Carbaryl
use
in
Agriculture
(Source
USGS
http://
water.
wr.
usgs.
gov/
pnsp/
use92/
mapex.
html)
3.0
Integrated
Risk
Characterization
Introduction
Carbaryl
is
a
widely
used
insecticide,
and
as
a
result
of
normal
agricultural
and
nonagricultural
uses,
it
is
commonly
detected
in
the
environment.
Carbaryl
and
its
primary
degradate
1
naphthol
are
fairly
mobile
and
slightly
persistent.
In
general
they
are
not
likely
to
persist
or
accumulate
in
the
environment.
Under
acidic
conditions
with
limited
microbial
activity
they
may
persist.
Carbaryl
dissipates
in
the
environment
by
abiotic
and
microbially
mediated
degradation.
The
major
degradation
products
are
CO2
and
1
naphthol
which
is
further
degraded
to
CO2.
Carbaryl
is
stable
to
hydrolysis
in
acidic
conditions
but
hydrolyzes
in
neutral
(pH
7
half
life
12
days)
and
alkaline
(pH
9
half
life
=
5
hours
environments.
Carbaryl
is
degraded
by
photolysis
in
water
with
a
half
life
of
21
days.
Under
aerobic
conditions
the
compound
degrades
rapidly
by
microbial
metabolism
with
half
lives
of
4
to
5
days
in
soil
and
aquatic
environments.
In
anaerobic
9
environments
metabolism
is
much
slower
with
half
lives
on
the
order
of
2
to3
months.
Carbaryl
is
mobile
in
the
environment
(Kf
=1.7
to
3.5).
The
major
metabolite
of
carbaryl
degradation
by
abiotic
and
microbially
mediated
processes
is
1
naphthol.
Only
limited
information
is
available
for
the
environmental
transport
and
fate
1
naphthol.
While
guideline
studies
were
not
submitted
specifically
for
the
degradate
open
literature
information
suggests
that
it
is
less
persistent
and
less
mobile
then
parent
carbaryl.
Carbaryl
is
commonly
detected
in
surface
water
monitoring
studies.
Concentrations
are
generally
low
(less
than
1
:
g/
L),
and
the
maximum
reported
value
is
less
than
10
:
g/
L.
In
groundwater
carbaryl
is
detected
less
often
and
at
lower
levels
(generally
less
than
0.01
:
g/
L).
Because
of
the
relatively
limited
persistence
of
the
compound
in
the
environment
it
is
unlikely
that
non
targeted
monitoring
studies
will
detect
the
maximum
concentrations
that
occur.
Because
only
very
limited
targeted
data
of
uncertain
quality
exists
modeling
was
used
to
estimate
maximum
and
average
concentrations
that
may
occur.
Model
results
suggest
that
concentrations
in
surface
water
resulting
from
normal
agricultural
practices
are
high
enough
to
adversely
effect
a
variety
of
aquatic,
estuarine
and
marine
species.
Aquatic
Organisms
Most
carbaryl
uses
are
not
likely
to
pose
acute
or
chronic
risks
to
freshwater
fish,
nor
an
acute
risk
to
estuarine/
marine
fish.
Most
carbaryl
uses,
however,
are
likely
to
pose
acute
and
chronic
risks
to
freshwater
invertebrates,
and
acute
risk
to
estuarine/
marine
invertebrates.
On
an
acute
basis,
carbaryl
is
highly
to
slightly
toxic
to
freshwater
fish
(LC50
=
0.25
20
ppm),
moderately
toxic
to
estuarine/
marine
fish
(LC50
=
2.6
ppm),
very
highly
toxic
to
freshwater
aquatic
invertebrates
(LC50
=
1.7
26
ppb),
and
very
highly
toxic
to
estuarine/
marine
aquatic
invertebrates,
especially
mysids.
Carbaryl's
main
degradate,
1
naphthol,
is
highly
to
moderately
toxic
to
freshwater
fish
(LC50
=
0.75
1.6
ppm),
moderately
toxic
to
estuarine/
marine
fish
(LC50
=
1.2
1.8
ppm),
highly
toxic
to
freshwater
invertebrates
(LC50
=
0.7
ppm),
and
highly
toxic
to
moderately
toxic
to
estuarine/
marine
invertebrates
(0.21
2.5
ppm).
EECs
for
1
naphthol
can
not
be
calculated
because
of
a
lack
of
fate
and
transport
data.
Exposure
to
sublethal
carbaryl
levels
in
laboratory
studies
are
known
to
adversely
affect
survival
of
freshwater
fish
young
(NOAEC
=
0.25
ppm)
and
reproduction
in
freshwater
invertebrates
(NOAEC
=
3.3
ppb).
NOAEC
values
for
estuarine/
marine
fish
and
invertebrates
have
not
been
established
because
of
missing
data
on
chronic
toxicity
to
estuarine/
marine
fish.
Although
EEC
scenarios
for
aquatic
organisms
were
modeled
using
three
different
kinds
of
application
rate
data
(maximum
label,
maximum
reported
Doane,
and
"average"
rates),
the
LOC
exceedances
are
minimally
affected
by
the
type
of
usage
data.
The
acute
risk
LOC
for
freshwater
fish
is
exceeded
for
one
of
five
use
scenarios
modeled
(citrus)
at
all
three
application
rates,
and
the
chronic
risk
LOC
is
not
exceeded
for
any
scenario,
at
any
use
rate
(Table
1).
10
Exposure
to
certain
sublethal
carbaryl
concentrations
can
produce
deleterious
effects
in
freshwater
fish.
When
the
freshwater
murrell
(Channa
punctatus)
is
exposed
to
concentrations
in
the
1666
3730
ppb
range,
the
resulting
inhibition
of
acetycholinesterase
(AChE)
can
cause
thyroid
and
gonadal
dysfunction
(Ghosh
et
al.,
1990).
However,
this
study
was
performed
at
concentration
levels
well
above
the
highest
peak
concentration
modeled
for
carbaryl
(Table
5)
and,
therefore,
does
not
provide
an
indication
as
to
potential
effects
under
field
conditions.
In
the
fathead
minnow
(Primephales
promelas),
exposure
to
concentrations
in
the
0.008
0.68
mg/
l
(8
680
ppb)
prevented
reproduction
and
decreased
survival
only
at
the
highest
test
concentration
(Carlson
1972).
The
NOAEC
determined
by
this
study,
0.21
mg/
l
(210
ppb),
is
at
the
high
end
of
the
peak
EECs
predicted
from
models
for
only
the
citrus
scenario
(Table
5)
and
well
below
the
peak
EECs
predicted
for
the
other
four
scenarios
that
were
modeled
Table
1.
Aquatic
organisms:
acute
and
chronic
Risk
LOC
exceedances
and
RQs
for
nongranular
carbaryl
uses
Acute
Risk
Chronic
Risk
Label
Max
Max
Rep
"Average"
Label
Max
Max
Rep
"Average"
Freshwater
Fish
LOC
Exceed.
1
1/
5
1/
5
1/
5
0/
5
0/
5
0/
5
RQs
1.
1
0.
93
0.
58
Estuarine/
Marine
Fish
LOC
Exceed.
1
0/
5
0/
5
0/
5
no
data
no
data
no
data
RQs
Freshwater
Inverts
LOC
Exceed.
1
5/
5
5/
5
5/
5
5/
5
5/
5
5/
5
RQ
Ranges
1.
5
48.9
1.
1
4
0.8
25.9
3.
3
91.3
2.
0
74.7
1.
7
44.7
Estuarine/
marine
Inverts
LOC
Exceed.
1
5/
5
5/
5
5/
5
no
data
no
data
no
data
RQ
Ranges
1.
5
48.1
1.
0
40.7
0.
8
25.4
1
No.
use
scenarios
for
which
RQ
is
greater
than
LOC/
total
No.
use
scenarios
examined
(acute
LOC
=
0.5,
chronic
LOC
=
1)
At
relatively
high
concentrations,
carbaryl
can
adversely
affect
amphibians'
development
and
behavior.
For
instance,
Bridges
(2000)
reports
that
acute
exposure
to
carbaryl
in
southern
leopard
frogs
during
development,
from
egg
to
tadpole,
results
in
a
higher
rate
of
deformities
relative
to
control
tadpoles.
Nearly
18%
of
the
tadpoles
exhibited
some
type
of
developmental
deformity,
including
both
visceral
and
limb
malformities,
compared
to
a
single
deformed
(less
than
1%)
control
tadpole.
Activity
of
plains
leopard
frog
tadpoles
exposed
to
carbaryl
diminishes
by
nearly
90%
at
3.5
mg/
L
and
ceases
completely
at
7.2
mg/
L
(Bridges,
1997).
Although
under
the
reported
test
conditions
potential
consequences
of
reduced
activity
and
swimming
performance
can
lead
to
increased
vulnerability
to
predation,
slower
growth,
and
failure
to
complete
metamorphosis,
tests
concentrations
are
considerably
higher
than
the
highest
surface
water
EECs
calculated
for
carbaryl.
Testing
at
or
below
maximum
EEC
is
needed
to
better
understand
if
amphibians
are
indeed
likely
to
be
at
risk
when
exposed
to
carbaryl
at
concentrations
likely
to
occur
under
field
conditions.
It
is
also
possible
that
the
PRZM/
EXAMS
pond
modeling
may
not
be
conservative
enough
for
amphibians
breeding
in
temporary
pools
and
other
short
lived
aquatic
habitats
exposed
to
carbaryl
11
through
runoff
and/
or
spray
drift.
EFED
is
concerned
about
the
behavioral
and
developmental
effects
of
carbaryl
on
amphibians;
when
appropriate
test
procedures
have
been
developed
to
examine
these
effects,
EFED
will
request
that
carbaryl
undergo
these
studies.
The
acute
risk
LOC
for
estuarine/
marine
fish
is
not
exceeded
for
any
use
scenario
modeled,
at
any
use
rate,
indicating
that,
except
for
the
oyster
bed
use
in
Washington
State,
carbaryl
uses
are
unlikely
to
pose
an
acute
risk
to
these
organisms.
The
absence
of
core
chronic
toxicity
data
precluded
the
calculation
of
an
RQ
for
estuarine/
marine
fish.
Information
from
the
open
literature,
however,
indicates
that
exposure
to
sublethal
levels
of
carbaryl
can
produce
certain
adverse
effects
in
some
species.
According
to
Weis
and
Weis
(1974),
laboratory
exposure
of
the
silverside
(Menidia
menidia)
to
a
single
dose
of
carbaryl
(100
ppb)
resulted
in
the
temporary
disruption
of
schooling
behavior,
consisting
mainly
of
a
spreading
out
of
the
school
over
a
larger
area.
This
change
in
behavior
was
observed
after
24
h
exposure.
Returning
the
fish
to
carbaryl
free
water
did
not
bring
about
a
return
of
normal
schooling
patterns
until
72
hours.
This
effect
was
attributed
to
the
accumulation
of
carbaryl
degradate1
naphthol.
Aerial
carbaryl
applications
to
tideland
areas
in
Washington
State,
at
7.5
8
lb
ai/
acre,
for
control
of
burrowing
shrimp
in
commercial
oyster
beds
are
known
to
pose
a
significant
acute
risk
to
fish
inhabiting
treated
mudflats
or
trapped
in
shallow
pools.
Estimates
of
potential
fish
kills
range
from
15,000
to
96,000
following
each
treatment
(MRID
419826
06).
Exposure
to
sublethal
carbaryl
levels
may
also
inhibit
acetylcholinesterase
in
fish
in
subtidal
areas
near
treated
sites,
resulting
in
a
temporary
impairment
of
burying
behavior
and
increasing
exposure
to
predators
(Pozorycki,
1999).
Along
with
the
burrowing
shrimp,
other
invertebrate
populations
inhabiting
treated
mudflats,
which
constitute
a
food
source
for
fish,
are
temporarily
reduced
or
eliminated.
There
may
be
up
to
100%
mortality
of
Dungenese
crab
populations
following
carbaryl
applications.
However,
some
invertebrates
recolonize
the
treated
areas
within
two
weeks
(MRID
419826
06),
and
most
populations
of
invertebrates
recover
in
less
than
two
months
(Brooks
1993).
Once
established,
the
oyster
beds
provide
a
suitable
environment
for
a
species
diverse
community,
as
many
plants
and
invertebrates,
which
are
normally
rare
or
absent
in
barren
mudflats,
readily
grow
on
or
in
between
oyster
shells
(MRID
419826
06).
Since,
on
average,
tideland
areas
are
treated
once
every
six
years,
adverse
effects
on
the
aquatic
biota
are
temporary.
Potential
nonchemical
pest
management
methods
identified
include
alternative
culture
techniques,
mechanical
control,
enhancement
of
shrimp
predators,
and
electrofishing.
Carbaryl
application
techniques
that
reduce
drift,
such
as
direct
injection
of
carbaryl
into
the
sediment,
should
be
also
further
explored.
In
addition,
improvements
in
the
forecasting
of
shrimp
infestation
and
the
refinement
of
current
action
thresholds
may
help
to
decrease
the
frequency
and
amount
of
carbaryl
applications
without
affecting
effectiveness.
Environmental
concentrations
of
carbaryl
resulting
from
normal
agricultural
uses
have
been
shown
to
have
effects
on
invertebrate
populations
and
individuals.
Both
acute
and
chronic
risk
LOCs
are
exceeded
for
freshwater
invertebrates
for
all
five
carbaryl
aquatic
use
scenarios
modeled
at
maximum
label,
maximum
reported,
and
"average"
use
rates,
indicating
that
most
carbaryl
uses
are
likely
to
pose
acute
and
chronic
risks
to
freshwater
invertebrates.
Emergence
of
aquatic
insects,
such
as
damselflies,
can
also
be
severely
reduced
after
10
12
days
exposure
to
100
µg/
L
of
carbaryl
(Hardersen
and
Wratten,
1998).
In
a
mesocosm
study,
at
carbaryl
concentrations
above
20
µg/
L
12
Daphnia
were
no
longer
found
and
at
concentrations
greater
than
50
µg/
L,
all
cladocerans
were
eliminated,
resulting
in
increased
algal
biomass
due
to
repartitioning
of
biomass
from
zooplankton
to
phytoplankton
(Havens,
1995).
Studies
with
the
freshwater
snail
(Pomaca
patula)
have
shown
that
increased
acetyl
cholinesterase
(AChE)
inhibition
occurs
concurrently
with
the
bioconcentration
of
carbaryl
after
72
hour
exposure
at
3.2
µg/
g
(Mora
et
al.,
2000).
The
acute
LOC
for
estuarine/
marine
invertebrates
is
exceeded
for
all
five
carbaryl
use
scenarios
assessed
at
maximum
label,
maximum
reported,
and
"average"
application
rates,
indicating
that
estuarine/
marine
invertebrates
inhabiting
intertidal
zones
and
estuaries
near
areas
where
carbaryl
is
applied
are
likely
to
be
at
risk.
Terrestrial
Organisms
Three
different
kinds
of
nongranular
carbaryl
usage
data
were
considered
for
assessing
risk
to
terrestrial
animals:
maximum
label
rates,
maximum
reported
(Doane
data
available
for
42
uses)
rates,
and
QUA
"average"
rates.
In
most
cases
the
LOC
exceedance
pattern
was
not
significantly
affected
by
the
kind
of
usage
data
used
to
calculate
risk
quotients.
Acute
risk
quotients
indicate
that,
although
none
of
nongranular
carbaryl
uses
may
pose
an
acute
risk
to
birds,
all
nongranular
uses
present
a
chronic
risk
to
birds.
All
granular
uses
are
likely
to
pose
an
acute
risk
to
20
g
birds,
and
all
granular
uses,
except
for
cucurbits,
legumes,
wheat,
millet,
and
sugar
beet,
also
represent
a
risk
to
180
g
birds,
while
only
the
trees
and
ornamentals,
turfgrass,
and
tick
control
uses
pose
a
risk
to
1000
birds.
All
nongranular
and
granular
uses
are
likely
to
pose
an
acute
risk
to
15
g
and
35
g
mammals.
All
nongranular
uses
pose
a
chronic
risk
to
mammals.
Table
2
summarizes
LOC
exceedances
as
well
as
the
respective
RQ
ranges
for
nongranular
uses.
The
Agency
is
aware
of
only
a
few
carbaryl
related
mortality
incidents
for
mammals
and
birds,
all
involving
small
numbers
of
individuals.
Although
few
in
number
and
magnitude,
considering
that
few
mortality
incidents
are
actually
detected
and
reported,
these
known
incidents
suggest
that
a
certain
level
of
acute
risk
to
birds
and
mammals
from
exposure
to
carbaryl
does
exist
under
field
conditions.
13
Table
2.
Avian
and
Mammalian
Acute
and
Chronic
Risk
LOC
Exceedances
and
highest
RQs
for
Nongranular
Carbaryl
Uses
at
Maximum
Label,
Maximum
Reported,
and
QUA
Average
application
rates.
Acute
Risk
Chronic
Risk
Label
Max
Max
Rep
"Average"
Label
Max
Max
Rep
"Average"
Birds
LOC
Exceed.
1
0/
74
0/
42
0/
70
73/
74
34/
42
39/
70
RQs
N/
A
N/
A
N/
A
1.5
12.8
1.
0
12.0
1.
0
4.
2
Mammals
LOC
Exceed.
1
74/
74
41/
42
63/
70
72/
74
42/
42
69/
70
RQs
0.
76
12.12
0.60
11.36
0.53
4.02
3.0
48.0
1.
5
45.0
1.
5
15.9
1
No.
uses
for
which
the
highest
RQ
is
greater
than
LOC/
total
No.
uses
examined
(acute
LOC
for
birds
=
1;
acute
LOC
for
mammals
=
0.5,
chronic
LOC
for
birds
and
mammals
=
1)
Based
on
a
rock
dove
LD50
of
1,000
mg/
kg
and
a
mallard
LD50
greater
than
2,000
mg/
kg,
technical
carbaryl
can
be
classified
as
slightly
to
practically
nontoxic
to
birds
on
an
acute
basis.
LD50
values
for
carbaryl
as
low
as
16.2
mg/
kg
and
56.2
mg/
kg
have
been
reported
for
the
starling
and
the
red
winged
blackbird,
respectively
(Schafer
et
al.,
1983).
Although
these
data
are
based
on
simple
screening
tests,
and
are
therefore
not
reliable
for
risk
assessment
purposes,
they
do
suggest
that
passerine
birds
may
be
significantly
more
sensitive
to
carbaryl
exposure
than
non
passerine
birds.
Thus,
the
registrant
is
strongly
encouraged
to
submit
acute
oral
toxicity
tests
with
passerine
avian
species.
This
risk
assessment
is
using
the
dove
LD50
(lower
95%
confidence
interval
=
1,000
mg/
kg)
to
calculate
acute
RQs
for
granular
carbaryl.
On
a
subacute,
dietary
basis,
carbaryl
is
practically
nontoxic
to
birds.
The
quail
LC50
is
greater
than
5,000
ppm,
and
an
LC50
greater
than
10,000
ppm
is
reported
for
the
Japanese
quail
(Coturnix)
by
Hill
and
Camardese
(1986).
On
a
chronic
basis,
the
NOAEC
is
300
ppm
for
the
mallard
duck,
based
on
adverse
reproduction
effects
including
reduced
egg
production,
decreased
fertility,
and
increased
incidence
of
cracked
eggs.
For
this
risk
assessment,
the
quail
LC50
(>
5,000
ppm)
and
the
duck
NOAEC
(300
ppm)
are
used
to
calculate
the
subacute
dietary
and
chronic
RQs,
respectively.
The
avian
acute
risk
level
of
concern
(LOC)
is
not
exceeded
for
any
nongranular
carbaryl
use,
at
maximum
or
less
than
maximum
label
application
rates.
The
avian
chronic
risk
LOC
is
exceeded
for
almost
all
(73
of
74)
uses
considered
at
maximum
label
rates,
for
34
of
42
uses
at
maximum
reported
rates,
and
for39of
70
uses
at
"average"
rates.
The
avian
acute
LOC
is
exceeded
for
20
g
birds
for
all
granular
carbaryl
uses
(RQs:
0.52
4.76).
For
180
g
birds,
the
acute
LOC
is
exceeded
for
the
trees/
ornamentals,
turfgrass,
and
tick
control
uses
(RQ:
0.53).
No
acute
LOCs
are
exceeded
for
birds
in
the
1000
g
weight
class
for
any
of
the
granular
carbaryl
uses.
Carbaryl
is
moderately
toxic
to
small
mammals
on
an
acute
oral
basis
(rat
LD50
=
301
mg/
kg)
and,
based
on
decreased
fetal
body
weights
and
increased
incomplete
ossification
of
multiple
bones
in
the
laboratory
rat
(LOAEC
=
600
ppm,
NOAEC
=
80
ppm),
has
the
potential
for
mammalian
chronic
effects.
14
As
summarized
in
Table
2,
at
maximum
label
rates
the
mammalian
acute
LOC
is
exceeded
for
all
74
nongranular
carbaryl
uses,
and
the
chronic
risk
LOC
is
exceeded
for
70
of
the
uses.
RQs
based
on
maximum
reported
rates
for
42
uses
exceed
the
acute
LOC
for
41
uses,
while
the
chronic
risk
LOC
is
exceeded
for
all
42
uses.
When
"average"
rates
are
used
to
calculate
RQs
for
70
nongranular
uses,
the
acute
risk
LOC
is
exceeded
for
63
uses,
and
the
chronic
risk
LOC
is
exceeded
for
69
uses,
indicating
that
LOC
exceedances
are
minimally
affected
when
mammalian
RQs
are
calculated
using
less
than
maximum
label
rates.
Information
available
in
the
open
literature
suggests
potential
reproduction
effects
of
carbaryl
on
mammals.
Several
field
and
laboratory
studies
report
significant
reproduction
effects
for
several
species
of
mammals,
including
reduced
reproduction,
disturbances
in
spermatogenesis,
pathological
pregnancy,
increased
embryonal
resorption,
increased
percentages
of
infertile
females,
and
males
with
underdeveloped
testicles
(Gladenko
et
al.,
1970,
Smirnov
et
al.,
1971,
Krylova
et
al.,
1975,
Pomeroy
&
Barrett,
1975).
Others
report
only
slight
effects
(Anonymous,
1969,
Dougherty
et
al.,
1971,
Narotsky
and
Kavlock,
1995).
Some
fail
to
detect
any
reproduction
effects
(DeNorscia
and
Lodge,
1973,
Dougherty,
1975,
Chapin
et
al.,
1997).
Carbaryl
is
highly
toxic
to
honey
bees
(LC50
=
1.3
2.0
µg/
bee),
and
moderately
to
highly
toxic
to
a
wide
range
of
other
beneficial
insects,
including
species
that
prey
on
or
parasitize
many
insect
pests.
Carbaryl
has
been
linked
to
numerous
bee
mortality
incidents
in
several
states,
which
is
not
surprising
given
its
effectiveness
as
a
broad
spectrum
insecticide
and
its
large
number
of
uses.
According
to
surveys
conducted
by
the
American
Beekeeping
Federation
and
the
Washington
State
Department
of
Agriculture,
carbaryl
is
one
of
the
pesticides
most
frequently
mentioned
as
being
associated
with
bee
kills
(Brandi
1997,
Johansen
1997).
To
minimize
risk
to
bees
and
other
pollinators,
all
carbaryl
containing
products
display
the
standard
pollinator
protection
language
in
their
labels.
As
indicated
by
precautionary
label
language,
carbaryl
can
cause
injury
to
some
terrestrial
plants.
Carbaryl,
used
as
a
fruit
thinning
agent
on
apples
and
pears,
may
cause
fruit
deformity
under
certain
environmental
conditions,
and
injury
to
tender
foliage
if
applied
to
wet
foliage
or
during
periods
of
high
humidity.
As
indicated
in
the
label,
carbaryl
may
also
cause
injury
to
Boston
ivy,
Virginia
creeper,
maidenhair
fern,
and
Virginia
and
sand
pines.
A
few
incidents
involving
carbaryl
injury
to
vegetable
crops
have
been
reported.
To
date,
no
terrestrial
plant
toxicity
studies
have
been
submitted
to
the
Agency.
To
fully
assess
carbaryl
risk
to
terrestrial
plants,
Tier
I
and,
if
appropriate,
Tier
II
Seed
Germination
and
Seedling
Emergence,
as
well
as
Vegetative
Vigor
studies
should
be
submitted
by
the
registrant.
15
Endangered
Species
The
endangered
species
LOC
for
birds
(0.1)
is
met
or
exceeded
for
72
of
74
nongranular
carbaryl
uses
at
maximum
label
use
rates,
for
18
of
70
carbaryl
uses
at
QUA
average
use
rates,
and
for
25
of
42
maximum
reported
use
rates.
The
endangered
species
LOC
is
exceeded
for
20
g
birds
for
all
granular
uses.
For
180
g
birds
it
is
exceeded
for
all
granular
uses,
except
cucumber,
melons,
pumpkin,
squash,
beans,
peas,
lentils,
cowpeas,
southern
peas,
wheat,
millet,
and
sugar
beets.
For
1000
g
birds,
the
endangered
species
LOC
is
reached
for
the
trees
and
ornamentals,
turfgrass,
and
tick
control
granular
uses.
The
mammalian
endangered
species
LOC
for
all
three
mammal
weight
categories
and
the
grass/
broadleaf
plants/
small
insects
food
items
is
exceeded
for
all
nongranular
uses
examined,
at
maximum
label
rates.
At
"average"
and
maximum
reported
use
rates,
the
endangered
species
LOC
for
15
g
mammals
feeding
on
short
grass
is
exceeded
for
all
carbaryl
uses.
The
endangered
species
LOC
is
exceeded
for
15
35
g
mammals
for
all
granular
uses.
The
endangered
species
LOC
for
freshwater
fish
is
exceeded
for
three
(sweet
corn,
field
corn,
and
citrus)
of
five
use
scenarios
modeled
and
for
the
citrus
scenario
at
less
than
maximum
label
rates.
For
marine/
estuarine
fish,
the
endangered
species
LOC
is
met
for
the
citrus
scenario
only
at
maximum
label
rates.
The
endangered
species
LOC
is
exceeded
for
freshwater
and
marine/
estuarine
aquatic
invertebrates
for
all
five
use
scenarios
at
maximum
and
less
than
maximum
label
use
rates.
The
uses
of
carbaryl
on
field
crops
(corn,
soybeans,
sorghum,
wheat),
forests
and
pasture/
rangeland
were
addressed
by
the
US
Fish
and
Wildlife
Service
(USFWS)
in
the
reinitiation
of
consultation
in
September
1989.
In
their
1989
Biological
Opinion,
USFWS
found
jeopardy
to
a
total
of
86
species
6
amphibians,
47
freshwater
fish,
27
freshwater
mussels,
and
5
aquatic
crustaceans.
Reasonable
and
Prudent
Alternatives
(RPA)
were
given
for
each
jeopardized
species.
Reasonable
and
Prudent
Measures
(RPM)
were
given
for
18
non
jeopardized
species
to
minimize
incidental
take
of
these
species.
Many
additional
species,
especially
aquatic
species,
have
been
federally
listed
as
endangered/
threatened
since
the
Biological
Opinion
of
1989
was
written,
and
determination
of
jeopardy
to
these
species
has
not
been
assessed
for
carbaryl.
In
addition,
endangered
insects,
birds
and
mammals
were
not
considered
in
the
1989
opinion
and
need
to
be
addressed.
Finally,
not
only
are
more
refined
methods
to
define
ecological
risks
of
pesticides
being
used
but
also
new
data,
such
as
that
for
spray
drift,
are
now
available
that
were
not
existent
in
1989.
The
RPAs
and
RPMs
in
the
1989
Biological
Opinion
may
need
to
be
reassessed
and
modified
based
on
these
new
approaches.
This
can
occur
once
the
program
is
finalized
and
in
place.
Endocrine
Disruption
Concerns
EPA
is
required
under
the
Federal
Food,
Drugs,
and
Cosmetics
Act
(FFDCA),
as
amended
by
Food
Quality
Protection
Act
(FQPA),
to
develop
a
screening
program
to
determine
whether
16
certain
substances
(including
all
pesticide
active
and
other
ingredients)
"may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(EDSTAC),
EPA
determined
that
there
was
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(EDSP).
When
the
appropriate
screening
and
or
testing
protocols
being
considered
under
the
Agency's
Endocrine
Disruptor
Screening
Program
have
been
developed,
carbaryl
may
be
subjected
to
additional
screening
and
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.
There
are
data
indicating
that
carbaryl
has
the
potential
for
endocrine
disruption
effects
on
fish.
Serum
and
pituitary
levels
of
gonadotropic
hormone
and
gonadotropin
releasing
hormone
(GnRH)
in
the
freshwater
murrell
(Channa
punctatus)
are
reduced
by
exposure
to
1.66
3.73
ppm
of
carbaryl
in
laboratory
and
paddy
field
tests
(Ghosh
et
al.,
1990).
The
decrease
in
GnRH
levels
could
be
explained
by
exposure
to
high
estrogen
levels,
acting
through
a
negative
feedback
pathway
to
inhibit
GnRH
release,
and
thus
the
release
of
gonadotropins
(Klotz
et
al.,
1997).
Plasma
and
ovarian
estrogen
levels
in
freshwater
perch
(Anabas
testudineus)
exposed
to
1.66
ppm
of
carbaryl
for
90
days
increase
until
day
15
and
then
decline,
relative
to
control
fish,
indicating
that
long
term
exposure
to
this
chemical
may
cause
an
inhibitory
effect
on
fish
reproduction
(Choudhury
et
al.,
1993).
Both
the
murrell
and
the
perch
studies,
however,
were
performed
at
concentrations
well
above
the
highest
peak
concentration
modeled
for
carbaryl
and,
therefore,
may
not
reflect
risk
under
field
conditions.
Furthermore,
a
number
of
field
and
laboratory
studies
report
reproduction
effects
with
mammals,
suggesting
that
the
possibility
of
endocrine
disruption
effects
on
wild
mammals
should
be
further
examined.
Uncertainties
The
absence
of
valid
chronic
toxicity
data
for
estuarine/
marine
fish,
estuarine/
marine
invertebrates,
and
amphibians,
as
well
as
the
lack
of
toxicity
data
for
aquatic
and
terrestrial
plants
represent
uncertainties
in
the
risk
assessment
for
carbaryl
that
need
to
be
addressed
through
the
submission
of
additional
required
data.
Additionally,
mammalian
chronic
RQs
were
based
on
a
rat
prenatal
development
study
NOAEC
(MRID#
44732901)
rather
than
the
more
traditional
use
of
a
2
generation
reproduction
study.
Field
studies
suggest
that
exposure
to
a
single
carbaryl
application
may
affect
reproduction
in
small
mammals.
17
Only
very
limited
information
is
available
for
the
environmental
fate
and
transport
of
the
major
carbaryl
degradate
1
Naphthol.
Without
additional
data
it
is
not
possible
to
develop
an
fate
profile
for
1
Naphthol.
Concentrations
in
surface
and
groundwater
can
not
be
estimated
without
data
on
the
stability
and
mobility
of
the
degradate
compound.
4.0
Environmental
Fate
Assessment
Exposure
Characterization
Using
acceptable
and
supplemental
environmental
fate
studies
submitted
by
the
registrant,
along
with
published
scientific
literature,
a
profile
of
the
fate
and
transport
of
carbaryl
in
the
environment
has
been
compiled.
This
information
is
sufficiently
complete
to
allow
the
evaluation
of
the
movement
and
fate
of
the
compound.
However,
existing
data
gaps
in
Soil
Photolysis,
Terrestrial
Field
Dissipation,
Aquatic
Field
Dissipation
and
degradate
fate
and
mobility
need
to
be
addressed
by
the
registrant.
Carbaryl
dissipates
in
the
soil
environment
by
abiotic
and
microbially
mediated
degradation.
The
major
degradation
products
are
CO2
and
1
naphthol,
which
is
further
degraded
to
CO2.
Carbaryl
is
stable
to
hydrolysis
in
acidic
conditions,
but
hydrolyzes
rapidly
in
alkaline
environments.
Carbaryl
is
degraded
by
photolysis
in
water,
with
a
half
life
of
21
days.
Under
aerobic
conditions
the
compound
degrades
rapidly
by
microbial
metabolism
with
half
lives
of
4
to
5
days
in
soil
and
aquatic
environments.
In
anaerobic
environments
metabolism
is
much
slower
with
half
lives
on
the
order
of
2
to3
months.
Carbaryl
is
mobile
in
the
environment
(Kf
=1.7
to
3.5).
Sorption
onto
soils
is
positively
correlated
with
soil
organic
content,
increasing
with
higher
soil
organic
content.
Table
3
summarizes
the
environmental
fate
characteristics
of
carbaryl.
An
analysis
of
the
significance
of
the
data
is
presented
in
this
section.
Monitoring
data
for
carbaryl
in
surface
water
and
groundwater
show
that
it
is
commonly
found
in
surface
water
and
groundwater.
In
surface
water
concentrations
are
generally
low
(less
than
1
:
g/
L)
and
the
maximum
reported
value
is
less
than
10
:
g/
L.
In
groundwater
carbaryl
is
detected
less
often
and
at
lower
levels
(generally
less
than
0.01
:
/L).
Available
monitoring
studies
and
data
sets
are
described
below.
Because
of
the
relatively
limited
persistence
of
the
compound
in
the
environment
it
is
unlikely
that
non
targeted
monitoring
studies
will
detect
the
maximum
concentrations
that
occur.
Because
of
the
limited
amount
of
data
available
and
because
of
potential
problems
with
extant
data
(described
below)
monitoring
data
are
of
limited
utility
in
developing
EECs
for
ecological
and
human
health
risk
assessment.
Therefore,
EFED
used
computer
modeling
to
estimate
surface
water
and
groundwater
concentrations
that
could
be
expected
from
normal
agricultural
use.
For
developing
surface
water
EECs
EFED
used
EPA
PRZM3.12
and
EXAMS
2.97.5
programs
to
estimate
the
concentration
of
carbaryl
in
surface
water.
For
ecological
risk
assessment
the
standard
pond
scenario
was
used.
For
human
health
risk
assessment
index
reservoir
scenarios
were
used.
3
"Average"
is
the
average
rate
as
determined
by
OPP/
BEAD
and
reported
in
the
a
memo
titled
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD.
4
Maximum
used
is
the
highest
rate
of
application
that
is
actually
reported
to
be
used
based
on
OPP/
BEAD
analysis
of
DoaneS
survey
data
by
Donald
Atwood,
Personal
communication,
January
31,
2001.
18
Several
application
rates
were
used
in
modeling:
the
maximum
allowed
for
the
specific
crop,
an
"average"
rate
3
,
and
the
maximum
rate
reported
to
actually
be
used
4
.
The
maximum
rate
was
taken
from
the
carbaryl
labels.
"Average
and
maximum
reported
rates
were
determined
by
EPA/
BEAD
based
on
data
collected
by
Doane
surveys
and
registrant
market
analysis.
EECs
varied
greatly
depending
on
the
geographic
location,
crop,
and
application
rate.
Modeling
"average"
and
maximum
reported
use
rates
yielded
EEC
values
generally
40
60%
lower
than
maximum.
EFED
normally
uses
the
maximum
allowed
application
rates
in
modeling.
In
this
assessment
other,
"less
then
maximum",
rates
were
modeled
in
order
to
evaluate
how
conservative
maximum
rates
modeling
estimates
are.
The
average
and
maximum
rates
may
or
may
not
be
representative
of
actual
use
rates
and
are
of
limited
certainty
due
to
the
quality
and
extent
of
the
data
available
to
calculate
them.
As
described
in
the
BEAD
chapter
the
average
application
rates
were
derived
by
dividing
total
pounds
used
by
the
overall
use
area.
The
resulting
average
does
not
represent
the
actual
average
applied
to
any
specific
area
and
is
not
relevant
for
fist
assessment.
The
maximum
reported
rate
was
determined
from
DOANES
survey
results.
These
data,
while
the
best
available,
are
very
limited.
The
number
of
farmers
surveyed
is
small,
often
only
one
or
two
per
state,
and
the
statistical
validity
of
the
results
are
not
known
but
it
is
highly
unlikely
that
the
survey
identified
the
actual
maximum
value.
The
maximum
calculated
EEC
resulted
from
use
on
citrus
in
Florida.
For
the
Index
Reservoir
scenario
using
maximum
label
rates,
acute
EEC
values
ranged
from
about
19
:
g/
L
from
sugar
beets
to
about
500
:
g/
L
from
citrus
(Table
6).
Chronic
EECs
ranged
from
about
2
to
28
:
g/
L.
These
values
are
higher
then
concentrations
observed
in
monitoring
studies
and
probably
represent
conservative
estimates
of
environmental
concentrations.
Modeling
results
are
higher
then
monitoring
data
because
of
the
limited
persistence
of
the
compound
in
most
surface
waters.
It
is
highly
unlikely
that
any
but
the
most
extensive
targeted
monitoring
would
capture
the
actual
peak
concentrations.
The
results
of
the
modeling
provide
a
conservative,
though
not
unreasonable,
estimate
of
possible
concentrations
in
drinking
water.
A
more
detailed
assessment
of
the
source
of
water
used
to
provide
drinking
water
and
the
relationship
between
the
areas
where
carbaryl
is
used
and
surface
water
sources
is
required
to
more
accurately
evaluate
possible
human
exposures.
Until
more
accurate
data
on
land
use
and
related
pesticide
application
is
available
and
can
by
linked
with
data
on
the
location
and
hydraulic
characteristics
of
the
water
bodies
it
is
not
possible
to
provide
more
accurate
assessment
of
possible
exposures.
A
more
detailed
description
of
modeling
is
presented
below,
and
model
input
files
are
attached
in
appendix
F.
19
Figure
2.
Generalized
carbaryl
degradation
pathway
Table
3:
Summary
of
Environmental
Chemistry
and
Fate
Parameters
For
Carbaryl
(See
Text
for
Analysis)
Parameter
Value
Reference
Selected
Physical/
Chemical
Parameters
Molecular
Weight
201.22
Water
Solubility
32
mg/
L
(ppm)
at
20
o
C
Suntio,
et
al.,
1988
Vapor
pressure
1.36
10
7
mm
Hg
(25
o
C)
Ferrira
and
Seiber,
1981
Henry's
Law
Constant
1.28
x
10
8
atm
m
3
mol
1
Suntio,
et
al.,
1988
Octanol/
Water
Partition
Kow
=
229
Windholz
et
al.,
1976
Persistence
Hydrolysis
t1/
2
pH
5
pH
7
pH
9
stable
12
days
3.2
hours
MRID
00163847,
44759301
Photolysis
t½
aqueous
21
days
MRID
41982603
Soil
photolysis
assumed
stable
No
valid
data
submitted
Soil
metabolism
T½
Aerobic
4
days
in
one
sandy
loam
soil
MRID
42785101
Anaerobic
t1/
2
=
72
days
Satisfied
by
162
3
Aquatic
metabolism
Aerobic
t1/
2
=
4.9
days
MRID
43143401
Anaerobic
t1/
2
=
72
days
MRID
42785102
Table
3:
Summary
of
Environmental
Chemistry
and
Fate
Parameters
For
Carbaryl
(See
Text
for
Analysis)
Parameter
Value
Reference
20
Major
Transformation
Products
Identified
in
the
Fate
Studies:
1
naphthol,
CO2
Minor
Transformation
Products
Identified
in
the
Fate
Studies:
5
hydroxy
l
naphthyl
methylcarbamate
(aerobic
soil
metabolism,
anaerobic
aquatic
)
1
naphthyl(
hydroxymethyl)
carbamate
(aerobic
soil
metabolism,
anaerobic
aquatic)
1,4
naphthoquinone
(aerobic
aquatic
metabolism,
anaerobic
aquatic)
(hydroxy)
naphthoquinones
(degradates
of
1
naphthol)
4
hydroxy
1
naphthyl
methylcarbamate
(anaerobic
aquatic)
1,5
naphthalenediol
(anaerobic
aquatic)
1,4
naphthalenediol
(anaerobic
aquatic)
Mobility/
Adsorption
Desorption
Batch
Equilibrium
Kf
(Koc)
=1.74
(207)
sandy
loam
2.04
(249)
clay
loam
sediment
3.00
(211)
silt
loam
3.52
(177)
silty
clay
loam
1/
n
values
ranged
from
0.78
0.84
MRID
43259301
Column
Leaching
slightly
mobile
in
columns
(30
cm
length)
of
sandy
loam,
silty
clay
loam,
silt
loam,
and
loamy
sand
soils
MRID
433207
01
Field
Dissipation
Terrestrial
Dissipation
Submitted
study
not
acceptable
MRID
419826
05
Forestry
Dissipation
Foliar
t1/
2
=
21
days
Leaf
Litter
t1/
2
=
75
days
Soil
t1/
2
=
65
days
MRID
43439801
Aquatic
Submitted
study
not
acceptable
MRID
4326001
Foliar
Dissipation
30
days
Default
value
Bioaccumulation
Accumulation
in
Fish
not
expected
due
to
low
Kow
21
Persistence
Chemical
Degradation
Processes
Hydrolysis
Carbaryl
hydrolysis
is
strongly
pH
dependant.
The
compound
is
stable
under
acidic
conditions
and
degrades
in
neutral
and
alkaline
systems
with
measured
half
lives
of
12
days
(pH
7)
and
3.2
hours
(pH
9).
Only
one
major
degradate
was
identified,
1
naphthol
(MRID
44759301).
Chapman
and
Cole
(1982)
measured
half
lives
of
2.0
weeks
(pH
=
7.0)
and
0.07
weeks
(pH
=
8).
Wolfe
et
al.
(1978)
reported
half
life
values
in
natural
pond
waters
at
pH
6.7
of
30
days
and
at
pH
7.2
of
12
days.
They
also
estimated
minimum
hydrolysis
half
life
in
acidic
conditions
of
1600
days.
Armbrust
and
Crosby
(1991)
reported
hydrolysis
half
lives
in
filtered
seawater
of
24
hours
at
pH
7.9
and
23
hours
at
pH
8.3.
The
major
degradation
product
was
1
naphthol
which
was
stable
to
further
hydrolysis.
Photolysis
Aqueous
Photolysis
In
an
aqueous
photolysis
study,
carbaryl,
with
an
initial
concentration
of
10.1
mg/
L,
degraded
in
a
pH
5
solution
with
a
half
life
of
21
days
after
correction
for
dark
controls(
MRID
41982603).
The
only
degradate
identified
was
1
naphthol.
Wolfe
et
al.
(1978)
reported
a
photolysis
half
life
in
distilled
water
at
pH
5.5
of
45
hours.
In
filtered
seawater
carbaryl
degraded
rapidly
to
1
naphthol
under
artificial
sunlight
(290
360
nm)
with
a
half
life
of
5
hours.
The
degradation
product,
1
naphthol,
was
degraded
very
rapidly
with
half
life
of
less
than
1
hour
(Armbrust
and
Crosby,
1991).
Soil
Photolysis
A
study
of
photolysis
(MRID
41982604)
on
soil
was
submitted;
however
the
study
was
determined
to
be
invalid.
No
data
on
the
possible
soil
photolysis
of
carbaryl
is
available.
In
view
of
this
data
gap,
it
is
assumed
that
the
compound
is
stable
to
photolysis
on
soil.
Microbially
mediated
Processes
Carbaryl
is
degraded
fairly
rapidly
by
microbial
processes
under
aerobic
conditions
and
more
slowly
under
anaerobic
conditions.
In
a
guideline
study
of
aerobic
soil
metabolism
carbaryl,
with
an
initial
concentration
of
11.2
mg/
kg,
degraded
with
a
half
life
of
4.0
days
in
sandy
loam
soil
incubated
in
the
dark
at
25
B
C
(MRID
42785101).
The
major
degradate
was
1
naphthol
which
further
degraded
rapidly
to
non
detectable
levels
within
14
days.
In
an
aerobic
aquatic
metabolism
study
carbaryl,
with
an
initial
concentration
of
9.97
mg/
L,
degraded
with
a
half
life
of
4.9
days
in
flooded
clay
loam
sediment
in
the
dark
at
25°
C
(MRID
43143401).
1
Naphthol
was
identified
as
a
major
nonvolatile
degradate.
Carbaryl
degraded
with
a
half
life
of
72.2
days
in
anaerobic
aquatic
sediment
with
an
initial
carbaryl
concentration
of
about
10
mg/
L;
1
naphthol
was
the
major
degradate.
Minor
degradates
included
5
hydroxy
1
naphthyl
methylcarbamate,
4
hydroxy
1
naphthyl
methylcarbamate,
1,5
naphthalenediol,
1,4
naphthalenediol,
1
naphthyl(
hydroxymethyl)
carbamate,
and
1,4
naphthoquinone
22
Liu,
et
al.
(1981)
studied
carbaryl
degradation
in
anaerobic
and
aerobic
fermenters
spiked
with
a
mixture
of
lake
sediment,
silt
loam
and
domestic
activated
sludge
and
buffered
to
pH
6.8.
They
reported
abiotic
degradation
half
lives
of
8.3
(aerobic)
and
15.3
(anaerobic)
days.
After
correcting
for
abiotic
controls,
when
carbaryl
was
used
as
the
sole
carbon
source
they
found
aerobic
and
anaerobic
metabolism
half
lives
of
54
and
11.6
days,
respectively.
When
glucose
and
peptone
were
added
co
metabolism
aerobic
and
anaerobic
metabolism,
half
lives
were
7.6
and
6.1
days
respectively.
A
number
of
soil
microorgamisms
have
been
identified
which
can
degrade
carbaryl
including
Pseudomonas
sp
(Chapalmadugu
and
Chaudhry,
1991;
Larken
and
Day,
1986),
Rhodoccus
sp.
(Larkken
and
Day,
1986),
Bacillus
sp.
(Rajagopal.
et
al.,
1984),
Arthrobacter
sp.
(Hayatsu
et
al.,
1999),
and
Achromobacter
sp
(Karns
et
al.,
1986).
Some
bacteria
are
capable
of
complete
degradation
to
CO2
(Chapalamadugu
and
Chaudhry,
1991)
while
some
stop
at
1
naphthol.
In
soils
it
appears
that
consortia
of
bacteria
are
able
to
degrade
parent
and
1
naphthol
completely
to
CO2.
Proposed
degradation
pathways
proceed
by
using
the
methylcarbarmate
side
chain
as
a
carbon
source,
converting
the
parent
to
1
naphthol.
1
naphthol
is
then
degraded
through
intermediates
salicylaldehyde,
salicylic
acid,
catechol,
and
gentisate
to
CO2
and
water
(Chapalamadugu
and
Chaudhry,
1991;
Hayatsu
et
al.,
1999).
Several
studies
have
shown
that
bacteria
isolated
from
soil
exposed
to
carbofuran
can
degrade
carbaryl
indicating
cross
adaption
by
microorganisms
allowing
degradation
of
compounds
with
similar
structure
(Karns
et
al.,
1986:
Chaudhry,
et
al.,
1988).
Carbaryl
degradation
utilizes
enzyme
systems
which
may
or
may
not
degrade
other
carbarmate
compounds
(Chapalamadugu
and
Chaudhry,
1991).
Mobility
Carbaryl
is
considered
to
be
moderately
mobile
in
soils.
Based
on
batch
sorption/
desorption
studies,
the
compound
has
Freundlich
Kf
values
of
<3.52.
Sorption
is
dependant
on
the
soil
organic
matter
content
and
increased
with
increasing
Koc.
Batch
Adsorption/
Desorption
Based
on
batch
equilibrium
experiments
(MRID
43259301)
carbaryl
was
determined
to
be
moderately
mobile
to
mobile
in
soils.
In
silty
clay
loam,
sandy
loam,
loamy
sand,
and
silt
loam
soils
and
clay
loam
sediment,
mobility
decreased
with
increasing
soil
organic
matter
content.
Adsorption
Koc
values
ranged
from
177
249.
Kf
values
were
1.74
for
the
sandy
loam
soil,
2.04
for
the
clay
loam
sediment,
3.00
for
the
silt
loam
soil,
and
3.52
for
the
silty
clay
loam
soil.
Corresponding
Koc
values
were
207,
249,
211,
and
177,
respectively,
and
1/
n
values
ranged
from
0.78
0.84.
Mobility
decreased
with
increasing
soil
organic
matter
content.
Sorption
showed
significant
hystereses
with
Freundlich
desorption
constants
(Kf(
des))
values
of
6.72
for
sandy
loam
soil,
6.78
for
clay
loam
sediment,
6.89
for
silt
loam
soil,
and
7.66
for
silty
clay
loam
soil.
1/
n
values
ranged
from
0.86
1.02.
Corresponding
desorption
Koc
values
were
800,
827,
485,
and
385,
respectively.
Literature
data
confirms
that
carbaryl
is
mobile.
Nkedi
Kizza
and
Brown
(1998)
reported
Kf
of
4.72
(1/
n
=
0.80)
for
soil
with
an
organic
content
of
590
mg/
Kg.
They
found
that
sorption
was
lower
on
subsoils
and
attributed
this
to
a
lower
organic
content.
The
reported
Koc
values
ranged
from
144
to
671.
23
Column
Leaching
In
column
leaching
experiments
(MRID
43320701),
carbaryl
residues
were
determined
to
be
slightly
mobile
in
columns
(30
cm
length)
of
sandy
loam,
silty
clay
loam,
silt
loam,
and
loamy
sand
soils
treated
with
aged
carbaryl
residues.
This
disparity
with
the
batch
experiments
may
possibly
be
explained
by
the
relatively
poor
extraction
recovery,
by
slow
desorption
kinetics
and
by
degradation
during
the
aging
period.
Unextracted
[
14
C]
labeled
residues
in
the
soils
prior
to
leaching
ranged
from
19.0%
of
the
recovered
in
the
loamy
sand
soil
to
39.7%
in
the
silty
clay
loam
soil.
The
study
author
believed
that
50%
of
the
carbaryl
applied
to
the
soil
had
degraded
prior
to
leaching.
Field
Dissipation
Studies
of
carbaryl
dissipation
in
terrestrial,
aquatic
and
forest
environments
have
been
submitted
by
the
registrant.
In
forest
environments
carbaryl
was
found
to
be
moderately
persistent
in
soil
(half
live
=
65
days)
and
leaf
litter
(half
live
=
75
days).
The
submitted
field
and
aquatic
dissipation
studies
were
determined
to
be
unacceptable,
and
did
not
provide
useful
information
on
movement
and
dissipation
of
carbaryl
or
its
degradation
products.
Field
dissipation
studies
conducted
in
the
1960s
and
1970s
in
terrestrial
(Fiche/
Master
ID
000108961
and
00159337),
aquatic
(Fiche/
Master
ID
001439080,
0124378,
00159337,
00159338,
00159339)
and
forestry
(Fiche/
Master
ID
00029738,
00159340,
00159341)
environments
and
submitted
in
the
1980s
have
been
reexamined.
When
they
were
initially
reviewed
they
were
not
considered
acceptable
for
a
number
of
reasons
including:
sampling
frequency
was
not
sufficient
to
allow
calculation
of
dissipation
rates,
degradates
were
not
identified
or
quantified,
soil,
sediment
and
water
were
not
sufficiently
characterized,
problems
with
analytical
method
specificity
and
validity,
insufficient
sampling
frequency
and
sampling
depth,
lack
of
data
on
irrigation
practices
measures.
These
studies
do
not
meet
current
levels
of
scientific
validity
required
to
be
considered
acceptable
and
do
not
provide
useful
information
on
field
dissipation
of
carbaryl
and
its
degradates.
The
data
requirements
for
terrestrial
and
aquatic
field
dissipation
have
not
been
fulfilled,
and
additional
studies
are
required.
Terrestrial
Field
Dissipation
Results
of
two
field
dissipation
studies
conducted
in
California
and
North
Carolina
were
submitted
(MRID
41982605).
Because
of
inappropriate
sampling
intervals,
poor
sample
storage
stability,
lack
of
degradate
monitoring,
rainfall
and
irrigation
that
were
less
than
evapotranspiration,
and
irrigation
water
with
high
pH,
these
studies
do
not
provide
reliable
information
on
the
rate
of
dissipation
of
parent
carbaryl
or
formation
of
degradation
products.
The
requirement
for
terrestrial
field
dissipation
has
not
been
fulfilled,
and
additional
information
is
required.
Because
of
problems
with
submitted
studies
additional
field
studies
are
required.
A
freezer
stability
study
was
reportedly
conducted
but
the
results
past
90
days
were
not
submitted.
There
was
apparently
significant
degradation
within
90
days.
Study
samples
were
analyzed
as
long
as
8
months
after
collection,
making
the
quality
of
the
data
highly
questionable.
Degradates
were
not
analyzed
in
either
study,
and
the
sampling
interval
was
insufficient
to
accurately
determine
the
dissipation
rate
for
carbaryl.
In
the
California
study
>80%
of
the
applied
24
carbaryl
apparently
dissipated
between
the
final
carbaryl
application
and
the
next
sampling
interval
(4
7
days
after
the
final
application).
In
the
NC
study
>
90
%
apparently
dissipated
between
application
and
the
next
sampling
event
(7days).
However,
in
both
studies
dissipation
after
7
days
suggested
a
half
life
on
the
order
of
weeks.
In
both
studies
rainfall
and
irrigation
were
less
than
evapotranspiration
so
the
data
can
not
be
used
to
assess
the
potential
for
carbaryl
to
leach
into
the
subsurface.
In
the
California
study,
irrigation
with
water
with
a
pH
of
8.0
was
applied
1
3
days
after
each
pesticide
application.
Because
carbaryl
hydrolysis
is
highly
pH
dependant
(
T1/
2
at
pH
9
=
3.2
hours)
this
may
have
resulted
in
significantly
more
rapid
degradation.
Forestry
Field
Dissipation
In
a
supplemental
forestry
field
dissipation
study
(MRID
43439801)
carbaryl
was
applied
on
a
pine
forest
site
in
Oregon.
Carbaryl
half
lives
were
found
to
be
21
days
on
foliage,
75
days
in
leaf
litter
and
65
days
in
soil.
At
the
time
of
treatment,
the
trees
of
primary
interest
(pine)
were
3
8
feet
tall.
Carbaryl
concentration
was
a
maximum
of
264
ppm
in
the
pine
foliage
at
2
days
posttreatment
28.7
ppm
in
the
leaf
litter
at
92
days,
0.16
ppm
in
the
upper
15
cm
of
litter
covered
soil
at
62
days,
and
1.14
ppm
in
the
upper
15
cm
of
exposed
soil
at
2
days.
Carbaryl
was
detected
in
the
leaf
litter
up
to
365
days
after
treatment,
and
in
the
litter
covered
soil
up
to
302
days
after
treatment.
Carbaryl
was
<0.003
ppm
in
water
and
sediment
from
a
pond
and
stream
located
approximately
50
feet
from
the
treated
area.
This
study
was
determined
to
provide
only
supplemental
information
because
degradation
products
were
not
identified
and
their
rate
of
formation
and
decline
was
not
determined.
Aquatic
Field
Dissipation
Results
of
aquatic
field
dissipation
studies
conducted
on
rice
in
Texas
and
Mississippi
were
submitted
(MRID
43263001).
The
studies
were
evaluated
and
found
to
be
unacceptable.
They
do
not
provide
useable
information
on
the
dissipation
of
carbaryl
and
1
naphthol
in
aquatic
field
conditions.
Frozen
storage
stability
data
were
provided
for
only
6
months,
although
the
water
samples
were
stored
for
up
to
14
months
and
the
soil
samples
were
stored
for
up
to
17.5
months
prior
to
analysis.
The
data
suggest
that
carbaryl
and
1
naphthol
degraded
significantly
during
storage.
In
the
six
months
of
storage
carbaryl
degraded
an
average
of
34
%
in
Texas
water
and
39%
in
from
Mississippi.
1
naphthol
degraded
50%
in
water
from
Texas
and
69%
from
Mississippi.
Degradation
did
not
appear
linear,
and
it
is
not
possible
to
extrapolate
out
to
14
months.
It
was
therefore
not
possible
to
evaluate
the
actual
concentrations
of
carbaryl
and
1
naphthol
in
the
samples
or
estimate
the
dissipation
rates.
Bioaccumulation
in
Fish
Because
of
the
low
octanol/
water
partition
coefficient
carbaryl
is
not
expected
to
significantly
bioaccumulate.
Reported
Kow
values
range
from
65
to
229
(Bracha,
and
O'Brian,
1966;
Mount,
M.
E.
and
Oehme,
1981;
Windholz
et
al.,
1976).
A
fish
bioaccumulation
study
reviewed
in
1988
(Chib,
1986,
Fiche/
Master
ID
00159342)
suggested
that
bioaccumulation
factors
were
14x
in
25
edible
tissue,
75x
in
visceral
tissue
and
45x
in
whole
fish.
Though
the
study
does
not
meet
current
acceptable
standards
it
does
support
the
conclusion
that
significant
bioaccumulation
is
not
expected.
No
additional
data
on
bioaccumulation
is
required
at
this
time.
Foliar
Dissipation
The
reported
rates
of
carbaryl
dissipation
from
foliar
surfaces
varies
from
1
days
to
30
days.
In
their
review
of
literature
data
on
pesticide
foliar
persistence,
Willis
and
McDowell
(1987)
report
that
carbaryl
dissipation
rates
varied
from
1.2
to
29.5
days.
In
the
submitted
forestry
field
dissipation
study
(MRID
43439801)
carbaryl
applied
to
pine
needles
dissipated
with
a
half
live
of
21
days.
For
terrestrial
risk
assessment
modeling
EFED
used
35
days
as
the
dissipation
half
life.
Atmospheric
Transport
Carbaryl
has
been
shown
to
be
transported
and
deposited
by
atmospheric
processes
(Waite,
et
al.,
1995;
Foreman,
et
al.,
2000;
Sanusi
et
al.,
2000).
As
with
all
chemicals
applied
by
aerial
or
ground
spray,
spray
drift
can
cause
exposure
to
non
target
organisms
downwind.
Beyer
et
al.,
(1995)
studied
spray
drift
from
aerial
application
to
rangeland
near
the
Little
Missouri
River
in
North
Dakota.
In
1991
carbaryl
was
applied
to
35130
ha
at
560
g/
ha
(0.62
lb)
A.
I.
A
152
m
nospray
buffer
zone
was
maintained.
River
water
samples
collected
1
hour
after
completion
of
spraying
had
a
mean
concentration
of
85.1
:
g/
l.
Concentration
decreased
over
time,
and
96
hours
after
application
the
mean
was
0.1
:
g/
l.
In
1993
a
similar
application
resulted
in
a
maximum
concentration
1
hour
after
spraying
of
12.6
:
g/
l
decreasing
to
5.14
:
g/
L
after
96
hours.
The
researchers
found
that
invertebrates
in
the
river
were
minimally
effected
while
fish
brain
acetylcholinesterase
activity
was
not
effected.
Vapor
phase
transport
and
particulate
transport
may
carry
the
compound
far
from
the
area
of
application.
In
the
atmosphere,
partitioning
between
particulate
and
gas
phase
is
a
function
of
temperature
and
changes
from
about
30%
vapor
phase
to
about
90%
when
temperature
increases
from
283
to
303
K
(Sanusi
et
al.,
1999).
This
suggests
that
atmospheric
transport
distance
and
deposition
are
a
function
of
temperature.
Carbaryl
has
been
detected
in
air
in
urban
and
suburban
areas
with
limited
influence
from
agricultural
spraying.
It
is
detected
more
frequently
and
generally
at
higher
concentrations
at
sampling
locations
in
urban
areas
than
in
agricultural
areas
(Foreman
et
al.,
2000).
Pesticide
concentrations
in
fog
often
are
higher
than
those
observed
in
rain
water
or
surface
water
and
may
represent
a
significant,
though
generally
overlooked,
route
of
exposure.
Schomburg
et
al.
(1991)
reported
carbaryl
concentrations
in
fog
ranging
from
0.069
to
4.0
:
g/
L.
26
1
Naphthol
Fate
and
Transport
Limited
information
is
available
for
the
environmental
fate
and
transport
of
the
major
carbaryl
degradate
1
Naphthol.
1
Naphthol
was
formed
in
laboratory
degradation
studies
and
represented
a
major
portion
of
the
applied
mass
(maximum
of
22
%
in
aerobic
aquatic
metabolism,
58%
in
aerobic
soil
metabolism
and
67%
in
photolysis).
1
Naphthol
was
not
persistent
in
the
studies
and
appears
to
have
degraded
more
rapidly
then
the
parent.
1
Naphthol
a
natural
product
and
is
also
formed
as
a
degradation
product
of
naphthalene
and
other
polycyclic
aromatic
hydrocarbons.
It
appears
to
degraded
more
rapidly
then
the
parent
in
the
submitted
studies
but
there
is
not
sufficient
information
the
develop
a
detailed
fate
profile.
While
guideline
studies
were
not
submitted
specifically
for
the
degradate,
literature
information
suggests
that
it
is
less
persistent
and
less
mobile
than
parent
carbaryl.
Armbrust
and
Crosby
(1991)
reported
that
1
Naphthol
was
stable
to
hydrolysis
in
filtered
seawater
at
pH
7.9
and
8.3.
Hydrolytic
degradation
of
1
naphthol
is
reported
to
be
due
to
reaction
with
dissolved
O2
and
is
highly
pH
dependant
(Karthikeyan
and
Chorover,
2000).
Oxidation
increases
with
pH
and
ionic
strength.
Below
pH
7
oxidation
is
minimal
and
reaches
a
maximum
at
about
pH
9.
Oxidation
of
1
naphthol
reportedly
results
in
production
of
(hydroxy)
naphthoquinones
and
dimer
coupled
reaction
products,
though
the
reaction
rates
for
1
naphthol
degradation
is
not
well
known
(Karthikeya
and
Chorover,
2000).
In
filtered
seawater
carbaryl
degraded
rapidly
to
1
naphthol
under
artificial
sunlight
(290
360
nm),
with
half
life
of
5
hours.
The
degradation
product,
1
naphthol,
was
degraded
very
rapidly
with
half
life
of
less
than
1
hour
(Armbrust
and
Crosby,
1991).
1
naphthol
is
degraded
rapidly
by
microbial
processes
in
aerobic
systems.
In
an
aerobic
soil
metabolism
study
(MRID
42785101)
1
naphthol
degraded
rapidly
to
non
detectable
levels
within
14
days.
Armbrust
and
Crosby
(1991)
reported
that
1
naphthol
degraded
in
unfiltered
seawater
to
below
detectable
level
within
94
hours.
Burgos
et
al.
(1999)
found
that
greater
than
90%
of
aqueous
1
naphthol
was
degraded
to
CO
2
within
10
days.
However,
they
found
that
sorption
to
soil
greatly
reduced
the
degradation
rate;
when
sorbed
degradation
was
greatly
slowed
to
25
40%
degradation
in
90
days.
No
guideline
information
was
submitted
on
1
naphthol
sorption.
Literature
information
suggests
that
it
is
not
strongly
sorbed.
Sorption
to
poorly
crystalline
aluminum
hydroxide
was
pH
dependant
and
appeared
to
occur
only
after
oxidation
(Karthikeyan
et
al.,
1999).
Hassett
et
al.
(1981)
reported
an
average
1
naphthol
Koc
of
431
(±
40)
for
10
of
the
16
soils
tested.
They
also
found
that
in
other
soils
with
very
low
organic
carbon
to
clay
ratios
clay
surfaces
controlled
sorption.
Additional
data
on
1
naphthol
sorption
is
required
to
fully
characterize
mobility.
27
Aquatic
Exposure
Assessment
Surface
Water
Five
crop
scenarios:
apples,
field
corn,
sweet
corn,
oranges
and
sugar
beets
scenarios
were
used
in
modeling
for
surface
water
EEC.
These
crops
were
chosen
as
representative
of
the
major
groups
of
crops
with
high
carbaryl
use
and
application
rates
that
would
result
in
high
potential
for
surface
water
contamination.
The
EEC's
generated
in
this
analysis
were
calculated
using
PRZM
for
simulating
runoff
from
an
agricultural
field
and
EXAMS
for
estimating
environmental
fate
and
transport
within
the
water
body.
Modeling
was
done
using
the
maximum
rate
on
label,
average
application
rate
and
maximum
rate
of
application
reported.
Two
sets
of
surface
water
simulations
have
been
done
for
carbaryl:
for
drinking
water
assessment
and
for
aquatic
ecological
exposure
assessment.
The
modeling
done
for
drinking
water
assessment
was
done
using
the
index
reservoir
watershed
scenario
(Jones,
et
al.,
2000)
and
calculated
values
were
corrected
for
Percent
Crop
Area
(PCA).
For
ecological
risk
assessment
modeling
was
done
using
the
standard
farm
pond
scenario.
The
standard
pond
scenario
used
by
EFED
simulates
a
ten
hectare
field
draining
into
a
one
hectare
static
pond
that
is
two
meters
deep
and
has
no
outlet.
It
is
assumed
that
evaporation
losses
and
inflow
from
rainfall
and
runoff
are
balanced.
The
inputs
used
are
similar
to
those
used
in
modeling
drinking
water
EECs
and
are
shown
in
Table
4.
EECs
generated
(Table
5)
were
compared
with
toxicological
information
described
below
to
estimate
the
risk
to
non
target
aquatic
organisms.
28
Table
4.
PRZM/
EXAMS
environmental
fate
input
parameters
for
Carbaryl
Parameter
Value
Data
source
Molecular
Weight
201.22
Solubility
32
mg/
L
(@
20°
C)
Suntio,
et
al.,
1988
Vapor
Pressure
(torr)
1.36
10
6
@
25°
C
Ferrira
and
Seiber,
1981
Henry's
Law
Constant
1.28
x
10
8
Suntio,
et
al.
1988
Hydrolysis
Half
life
pH
5
pH
7
pH
9
stable
12
days
3.2
hours
MRID
00163847
44759301
Soil
Photolysis
Half
life
(days)
stable
no
valid
data
submitted
Aquatic
Photolysis
Half
life
(days)
21
days
MRID
41982603
Aerobic
Soil
Metabolism
Half
life
4.
0
days
(n=
1
so
use
3x)
MRID
42785101
Aerobic
Aquatic
Metabolism
Half
life
4.
9
days
(n
=
1
so
use
3x)
MRID
43143401
Anaerobic
Aquatic
Metabolism
Half
life
72.2
days
MRID
42785102
Soil
Water
Partitioning
Coefficient
Kads
(Koc)
1.74
(207)
sandy
loam
2.0
(249)
clay
loam
3.0
(211)
silt
loam
3.5
(177)
silty
clay
loam
(Koc
=
209
for
SCIGROW)
MRID
43259301
There
are
a
number
of
factors
which
may
limit
the
accuracy
and
precision
of
the
PRZM/
EXAMS
modeling,
including
the
selection
of
realistic
exposure
scenarios,
the
quality
of
the
input
data,
the
ability
of
the
models
to
represent
the
real
world
and
the
number
of
years
that
were
modeled.
The
scenarios
that
are
selected
for
use
in
Tier
II
EEC
calculations
were
chosen
to
be
representative
of
uses
likely
to
produce
the
highest
concentrations
in
the
aquatic
environment.
The
EEC's
in
this
analysis
are
accurate
only
to
the
extent
that
the
model
represents
real
environments.
The
most
limiting
part
of
the
site
selection
is
the
use
of
the
standard
pond
with
no
outlet.
A
standard
pond
is
used
because
it
provides
a
basis
for
comparing
pesticides
in
different
regions
of
the
country
on
equal
terms.
The
models
also
have
limitations
in
their
ability
to
represent
some
processes
such
as
the
handling
of
spray
drift.
A
second
major
limitation
is
the
lack
of
validation
at
the
field
level
for
pesticide
runoff.
29
Table
5.
Tier
II
surface
water
estimated
environmental
concentration
(EEC)
values
derived
from
PRZM/
EXAMS
modeling
for
use
in
ecorisk
assessment
(Calculated
using
standard
pond.)
Use
Site,
Application
Method
Number
of
Applications
Per
Year
Application
Rate
(Pounds
A.
I.
per
Application)
Surface
Water
Acute
(ppb)
(1
in
10
year
peak
single
day
concentration)
21
day
(ppb)
(1
in
10
year)
60
day
(ppb)
(1
in
10
year)
Sweet
Corn
(OH),
air/
ground
Maximum
"Average"
Maximum
Reported
8
2
3
2
3.4
1
46
16
14
26
10
8
21
5
4
Field
Corn
(OH),
air/
ground
Maximum
"Average"
Maximum
Reported
4
2
2
2
1
1.5
28
12
18
16
6
9.5
10
3
5
Apples
(OR),
air/
ground
Maximum
"Average"
Maximum
Reported
5
2
2
2
1.2
1.6
8.6
4.5
6.0
4.9
2.5
3
4
1
2
Sugar
Beets
(MN),
air/
ground
Maximum
"Average"
Maximum
Reported
2
1
1
1.5
1.5
1.2
19
14
11
11
7
5
5
3
2
Oranges
(FL),
air/
ground
Maximum
"Average"
Maximum
Reported
4
2
3
5
3.4
4.3
274
145
232
137
67
112
79
33
55
Urban
and
Suburban
EFED
has
limited
tools
for
assessing
the
effects
of
pesticide
use
in
urban
and
suburban
settings
on
surface
water
and
groundwater
quality.
Carbaryl
is
extensively
used
in
such
nonagricultural
applications,
resulting
in
widespread
surface
water
contamination.
This
conclusion
is
based
on
monitoring
data.
In
urban
and
suburban
areas
small
streams
are
generally
greatly
affected
by
surface
runoff
and
water
collection
into
storm
sewers.
These
small
streams
can
provide
a
significant
habitat
for
aquatic
animals,
and
this
habitat
can
be
severely
degraded
by
runoff
of
urban
pesticides.
Garden
and
lawn
care
products
and
other
outdoor
uses
contribute
to
carbaryl
presence
in
storm
sewers
and
streams.
Monitoring
data
show
that
about
50%
of
urban
streams
have
measurable
concentrations
(>
0.01
:
g/
L)
of
carbaryl
compared
to
less
than
10%
of
agricultural
sites
(Larson,
et
al.,
1999).
Additional
information
is
needed
to
adequately
assess
the
environmental
impacts
of
urban
and
suburban
uses.
Targeted
surface
water
and
groundwater
monitoring
studies
are
required
to
more
adequately
understand
the
movement
of
the
compound
in
these
environments
and
to
provide
estimates
of
the
distribution
of
possible
exposures
from
urban
and
suburban
environments.
Estimated
Environmental
Concentrations
for
Terrestrial
Ecological
Risk
Assessment
For
terrestrial
EECs,
EFED
uses
the
concentration
of
a
chemical
on
food
items
derived
from
the
Kenaga
nomograph,
as
modified
by
Fletcher
et
al.
(1994).
The
nomograph
allows
estimation
of
the
concentration
of
pesticide
on
food
items
resulting
from
application,
based
on
a
large
set
of
actual
field
residue
data.
The
upper
limit
values
from
the
nomograph
represent
the
95th
percentile
30
of
residue
values
from
actual
field
measurements
(Hoerger
and
Kenaga,
1972).
Hoerger
Kenaga
pesticide
environmental
concentration
estimates
were
based
on
residue
data
correlated
from
more
than
20
pesticides
on
more
than
60
crops.
Representative
of
many
geographic
regions
(7
states)
and
a
wide
array
of
cultural
practices,
Hoerger
Kenaga
estimates
also
considered
differences
in
vegetative
yield,
surface/
mass
ratio
and
interception
factors.
In
1994,
Fletcher
et
al.
reexamined
the
Hoerger
Kenaga
simple
linear
model
(y=
B
1
x,
where
x=
application
rate
and
y=
pesticide
residue
in
ppm)
to
determine
whether
the
terrestrial
EEC's
were
accurate.
They
compiled
a
data
set
of
pesticide
day
0
and
residue
decay
data
involving
121
pesticides
(85
insecticides,
27
herbicides,
and
9
fungicides
from
17
different
chemical
classes)
on
118
species
of
plants.
They
concluded
that
Hoerger
Kenaga
estimates
needed
only
minor
modifications
to
elevate
the
predictive
values
for
forage
and
fruit
categories
from
58
to
135
ppm
and
from
7
to
15
ppm,
respectively.
Otherwise,
the
Hoerger
Kenaga
estimates
were
accurate
in
predicting
the
maximum
residue
values
after
a
1
lb
ai/
acre
application.
EFED
calculates
concentration
over
time
assuming
first
order
dissipation
from
plant
surfaces.
In
the
absence
of
reliable
foliar
dissipation
data
a
dissipation
half
life
of
35
days
is
used.
Published
literature
shows
that
carbaryl
dissipation
rates
vary.
and
are
among
the
highest
observed
for
any
pesticide.
(Willis
and
McDowell,
1987).
ELL
FATE,
a
spreadsheet
based
first
order
decay
model
was
used
to
calculate
concentration
over
time
for
multiple
applications
at
the
label
maximum,
"average,"
and
maximum
reported
application
rates.
A
more
thorough
description
of
the
model
calculations
and
ELL
FATE
outputs
are
attached
in
Appendix
D.
EEC
values
calculated
for
different
crop
applications
are
presented
in
Tables
4,
7,
8,
and
9,
Appendix
B.
5.0
Drinking
Water
Assessment
Water
Resources
Assessment
Chemical
characteristics
and
available
monitoring
data
indicate
that
carbaryl
has
the
potential
to
enter
surface
water
via
leaching
and
runoff
under
certain
conditions
and
has
limited
potential
to
leach
to
ground
water.
Carbaryl
tends
not
to
bind
tightly
to
soil,
aquifer
solids,
or
sediment.
Once
the
compound
has
entered
surface
water,
it
may
be
degraded
by
chemical
and
biological
processes.
Abiotic
degradation
by
photolysis
(t1/
2
=
21
days)
and
hydrolysis
in
alkaline
(t1/
2
=
3.2
hours
at
pH
9)
and
neutral
(t1/
2
=
12
days
at
pH
7)
waters
result
in
fairly
rapid
degradation
in
most
aqueous
environments.
Microbially
mediated
processes
also
contribute
to
fairly
rapid
degradation
of
the
parent
to
1
naphthol
and
CO2.
Aerobic
aquatic,
soil
aerobic
and
anaerobic
metabolism
studies
(t1/
2
=
5,
4,
and
72
days
respectively)
suggest
that
the
compound
is
broken
down
by
a
variety
of
metabolic
processes.
Under
certain
limited
conditions
carbaryl
may
be
expected
to
persist
in
the
environment.
Under
low
pH
conditions
the
compound
is
stable
to
hydrolysis.
In
anaerobic
environments
metabolism
is
fairly
slow
(t½
=
72
days).
Surface
water
monitoring
studies
show
that
carbaryl
is
the
second
most
widely
detected
insecticide
after
diazinon.
Carbaryl,
at
typically
low
concentrations,
is
found
in
greater
than
20
%
31
of
surface
samples
in
NAWQA
studies
at
concentrations
up
to
5.5
ppb.
Carbaryl
is
detected
more
frequently
in
non
agricultural
areas
(about
40%)
then
in
agricultural
areas
(about
5
%).
A
maximum
carbaryl
concentration
of
8.4
ppb
was
reported
for
surface
water
samples
in
the
California
DPR
surface
water
database.
Carbaryl
is
generally
not
widely
detected
in
groundwater
monitoring
studies
though
some
studies
have
found
concentrations
of
up
to
several
hundred
ppb.
Concentrations
as
high
as
610
µg/
L
have
been
detected
in
one
case
but
typical
groundwater
concentrations
are
much
lower.
NAWQA
studies
have
found
that
about
1
%
of
groundwater
samples
have
measurable
levels
(>
0.003
:
g/
L)
of
carbaryl,
with
a
maximum
concentration
of
0.02
µg/
L.
Targeted
studies
designed
to
measure
carbaryl
in
groundwater
are
not
available.
Drinking
Water
Exposure
Assessment
Based
on
chemical
properties,
existing
monitoring
data
and
computer
simulation
estimates
of
carbaryl
contamination
that
can
be
expected
in
surface
water
and
groundwater
as
a
result
of
normal
use
practices
have
been
determined.
Carbaryl
is
the
second
most
commonly
detected
insecticide
in
surface
water,
and
can
be
expected
to
contaminate
drinking
water
derived
from
surface
water
bodies.
Targeted
and
non
targeted
studies
regularly
detect
carbaryl
in
low
concentrations,
typically
below
1
µg/
L.
Monitoring
studies
suggest
that
about
20
%
of
surface
water
bodies
have
detectable
(>
0.01
:
g/
L)
levels
of
the
compound.
The
maximum
reported
value
in
surface
water
was
8.4
µg/
L.
Carbaryl
is
not
widely
detected
in
groundwater
studies.
Drinking
water
derived
from
groundwater
has
been
found
to
have
low
or
non
detectable
levels
of
carbaryl.
For
drinking
water
derived
from
groundwater,
the
acute
and
chronic
EEC
value
of
0.8
µg/
L
is
based
on
modeling
using
SCI
GROW.
It
must
be
noted
that
carbaryl
has
an
aerobic
metabolism
half
life
(4
days)
which
is
significantly
outside
the
range
of
values
for
which
SCI
GROW
may
be
valid
(17
1000
days).
Because
of
this
there
is
significant
uncertainty
in
the
SCI
GROW
value.
EFED
currently
does
not
have
more
advanced
groundwater
models,
and
targeted
studies
specifically
designed
to
evaluate
the
potential
for
carbaryl
to
move
to
groundwater
are
not
available.
Because
of
its
chemical
structure
carbaryl
is
somewhat
difficult
to
quantify
by
gas
chromatography.
Older
studies
using
GC
or
GC/
MS
generally
have
poor
recovery
and
quantitation
limits.
Because
of
this
difficulty
in
analysis
the
actual
concentration
of
carbaryl
in
groundwater
and
surface
waters
may
be
higher
than
reported.
More
recent
studies
using
HPLC/
MS
should
provide
better
data
on
the
true
extent
and
magnitude
of
water
contamination
from
the
use
of
carbaryl.
Drinking
Water
Modeling
Modeling
to
support
the
assessment
of
drinking
water
in
the
human
health
risk
assessment
was
done
for
five
scenario:
Florida
citrus,
Ohio
sweet
corn
and
field
corn,
Oregon
apples
and
Minnesota
sugar
beets.
These
scenarios
were
selected
to
represent
the
range
of
crops
and
use
rates
likely
to
result
in
higher
environmental
concentrations.
EECs
were
calculated
using
The
Pesticide
Root
Zone
Model
version
3.12
(PRZM)
(Carsel
et
al.,
1997)
and
EXAMS
2.97.5
(Exposure
Analysis
Modeling
System)
(Burns,
1997)
were
run.
PRZM
is
used
to
simulate
pesticide
transport
as
a
result
32
of
runoff
and
erosion
from
an
agricultural
field
and
EXAMS
estimates
environmental
fate
and
transport
of
pesticides
in
surface
water.
Weather
and
agricultural
practices
are
simulated
over
36
years
so
that
the
10
year
exceedance
probability
at
the
site
can
be
estimated.
A
partial
list
of
input
parameters
for
the
PRZM/
EXAMS
modeling
are
given
in
Table
4.
Simulations
were
run
using
the
maximum
application
rates,
average
rates,
and
maximum
reported
rates.
The
values
generated
by
the
models
were
multiplied
by
a
default
percent
crop
area
factor
(PCA)
which
accounts
for
the
fact
that
is
unlikely
for
any
basin
to
be
completely
planted
to
agricultural
crops.
For
human
health
assessment,
simulations
were
done
using
the
Index
Reservoir
scenario
in
Exams.
The
Index
Reservoir
and
PCA
are
described
in
Jones
et
al.,
2000.
The
EEC's
for
the
five
scenarios
simulated
are
shown
in
Table
6.
Input
files
for
PRZM/
EXAMS
modeling
is
included
in
Appendix
A.
The
maximum
calculated
EEC
resulted
from
use
on
citrus
in
Florida.
For
the
Index
Reservoir
scenario
using
maximum
label
rates,
acute
EEC
values
ranged
from
about
10
:
g/
L
from
sugar
beets
to
about
500
:
g/
L
from
citrus
(Table
6).
Chronic
EECs
ranged
from
about
2
to
28
:
g/
L.
These
values
are
higher
then
concentrations
observed
in
monitoring
studies
and
probably
represent
conservative
estimates
of
environmental
concentrations.
It
is
highly
unlikely
that
any
but
the
most
extensive
targeted
monitoring
would
capture
the
actual
peak
concentrations.
The
results
of
the
modeling
provide
a
very
conservative,
though
not
unreasonable,
estimate
of
possible
concentrations
in
drinking
water.
A
more
detailed
assessment
of
the
source
of
water
used
to
provide
drinking
water
and
the
relationship
between
the
areas
where
carbaryl
is
used
and
surface
water
sources
is
required
to
more
accurately
evaluate
possible
human
exposures.
In
Florida,
for
example,
the
majority
of
drinking
water
is
derived
from
groundwater
(>
90%)
so
high
surface
water
concentrations
do
not
necessary
indicate
high
exposure.
Until
more
accurate
data
on
land
use
and
related
pesticide
application
is
available
and
can
by
linked
with
data
on
the
location
and
hydraulic
characteristics
of
the
water
bodies
it
is
not
possible
to
provide
more
accurate
assessment
of
possible
exposures.
A
more
detailed
description
of
modeling
is
presented
below,
and
model
input
and
output
files
are
attached
in
Appendix
A.
Water
Treatment
Effects
The
Office
of
Pesticide
Programs
has
completed
a
preliminary
review
of
the
effects
of
d
r
i
n
k
i
n
g
w
a
t
e
r
t
r
e
a
t
men
t
o
n
p
e
s
t
i
c
i
d
e
s
i
n
w
a
t
e
r
(http://
www.
epa.
gov/
scipoly/
sap/
2000/
september/
sept00
sapdw
0907.
pdf).
This
review
indicates
that
standard
drinking
water
treatment,
consisting
of
flocculation/
sedimentation
and
filtration
does
not
substantially
affect
concentrations
of
pesticides
in
drinking
water.
Evidence
suggests
that
carbaryl
does
not
react
with
chlorine
or
hypoclorite
disinfection
products
in
water
treatment
but
is
rapidly
degraded
(T½
=
too
rapid
to
measure)
by
ozone
(Mason
et
al.,
1990).
Since
relatively
few
water
treatment
facilities
in
the
U.
S.
use
ozone
the
limited
data
available
do
not
indicate
that
carbaryl
is
likely
to
be
degraded
in
the
majority
of
treatment
plants.
33
Table
6.
Drinking
Water
EECs
Crop
Number
of
Applications
per
Year
Pounds
A.
I.
per
application
Surface
Water
Acute
(ppb)
(1
in
10
year
peak
single
day
concentration)
Surface
Water
Chronic
(ppb)
(1
in
10
year
annual
average
concentration)
Sweet
Corn
(OH)
(PCA
=
0.46)
Maximum
1
8
2
37
3.2
Average
2
2
3.
4
45
2.2
Maximum
3
Reported
3
1
15
0.9
Field
Corn
(OH)
(PCA
=
0.46)
Maximum
1
4
2
30
2.1
Average
2
2
1
13
0.6
Maximum
3
Reported
2
1.
520
1
Apples
(OR)
(PCA
=
0.87)
Maximum
1
5
2
144
9
Average
2
2
1.
2
12
0.7
Maximum
3
Reported
2
1.
625
1
Sugar
Beats
(MN)
(PCA
=
0.87)
Maximum
1
2
1.
519
2
Average
2
1
1.
5
12
1.1
Maximum
3
Reported
1
1.
2
9
0.
9
Oranges
(FL)
(PCA
=
0.87)
Maximum
1
4
5
494
28
Average
2
2
3.
4
246
11
Maximum
3
Reported
3
4.
26
411
16
Surface
Water
Monitoring
5.5
(Maximum
Observed
Concentration)
Groundwater
SCIGROW
Maximum
1
5
40.
8
0.
8
Groundwater
(NAWQA
Monitoring
Data)
0.02
0.02
1
Maximum
application
rate
on
label
2
Average
application
rate
from
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD
3
Maximum
rate
of
application
reported
in
Doanes
survey
data
Groundwater
Resources
Available
evidence
from
valid
scientific
studies
show
that
carbaryl
has
a
limited
potential
to
leach
to
ground
water.
As
a
result
of
normal
agricultural
use,
detections
of
carbaryl
residues
have
34
been
reported
in
groundwater
from
several
states.
As
reported
in
the
U.
S.
EPA.
Pesticides
in
Groundwater
Database
(Jacoby
et
al.,
1992)
carbaryl
was
detected
in
0.4%
of
wells
sampled.
Carbaryl
was
detected
in
California
(2
out
of
1433
wells),
Missouri
(11
out
of
325
wells),
New
York
(69
out
of
21027
wells)
Rhode
Island
(13
out
of
830
wells)
and
Virginia
(
11
out
of
138
wells).
The
maximum
concentration
detected
was
610
µg/
L
in
NY,
though
typically
the
measured
concentrations
were
significantly
lower.
The
EPA
STORET
database
was
queried
on
May
12,
1999
for
reports
of
measurements
of
carbaryl
in
groundwater.
The
database
contained
9389
records
indicating
that
analysis
was
done
for
carbaryl.
Out
of
these
only
4
reported
concentrations
above
the
detection
limits.
These
analyses
were
all
from
one
well
in
Cleveland,
OK
in
1988.
The
4
reported
concentrations
were
between
0.8
and
1
ppb.
Carbaryl
was
detected
at
greater
than
the
detection
limit
(0.003
µg/
L)
in
1.1
%
of
groundwater
samples
from
1034
sites
across
the
U.
S.
by
U.
S.
G.
S.
NAWQA
program.
The
maximum
observed
concentration
was
0.021
µg/
L.
Detections
were
mainly
from
three
use
sites:
wheat
(5.8
%
of
well
samples
from
wheat
land
use
),
orchards
and
vineyards
(1.7
%
of
well
samples
from
orchard
and
vineyard
land
use),
and
urban
(1.8%
of
urban
groundwater
samples).
Data
on
pesticides
in
groundwater
were
reviewed
by
Kolpin
et
al.
(1998)
and
updated
information
is
available
at:
http://
water.
wr.
usgs.
gov/
pnsp/
pestgw/.
Surface
Water
Resources
Monitoring
Data
Carbaryl
is
widely
detected
in
non
targeted
and
targeted
monitoring
studies.
Observed
concentrations
are
generally
low
(>
0.5
:
g/
L).
Carbaryl
is
not
very
persistent
in
most
surface
water
conditions
suggesting
that
the
wide
spread
occurrence
is
a
result
of
its
extensive
use
in
a
variety
of
applications.
Because
of
limitation
in
the
analytical
methods
used
there
is
some
uncertainty
in
the
quantitative
accuracy
of
carbaryl
analysis.
NAWQA
Carbaryl
is
the
second
most
widely
detected
insecticide
after
diazinon
in
the
USGS
NAWQA
program
(http://
water.
usgs.
gov/
nawqa/
nawqa_
home.
html).
Carbaryl
was
detected
in
46%
of
36
NAWQA
study
units
between
1991
and
1998.
The
reported
concentrations
are
believed
to
be
reliable
detections
but
have
greater
than
average
uncertainty
in
quantification.
The
data
in
the
NAWQA
database
are
amended
with
an
"E"
qualifier
to
indicate
the
variability
found
in
the
analysis.
This
suggests
that
the
reported
values
may
not
represent
the
maximum
concentrations
that
exist.
Carbaryl
(along
with
diazinon)
was
one
of
the
two
most
widely
detected
insecticides.
Out
of
5220
surface
water
samples
analyzed
1082,
or
about
21
percent,
were
reported
as
having
detections
greater
than
the
MDL.
The
maximum
reported
concentration
was
5.5
µg/
L.
For
samples
35
with
positive
detections
the
mean
concentration
was
0.11
:
g/
L,
with
a
standard
deviation
of
0.43
:
g/
L.
A
significant
portion
of
the
total
carbaryl
applied
was
transported
to
streams.
In
areas
with
high
agricultural
use
the
load
measured
in
surface
waters
was
relatively
consistent
across
the
country
at
about
0.1
percent
of
the
amount
used
in
the
basins
(Larson
et
al.,
1999)
http://
water.
wr.
usgs.
gov/
pnsp/
rep/
wrir984222/
load.
html.
The
estimated
carbaryl
use
on
in
agricultural
applications
is
about
2.5
million
pounds
suggesting
that
2,500
pounds
are
delivered
to
the
nations
streams
draining
agricultural
areas.
Streams
draining
urban
areas
showed
more
frequent
detections
and
higher
concentrations
than
streams
draining
agricultural
or
mixed
land
use
areas.
For
example
Kimbrough
and
Litke
(1996)
reported
that,
in
the
South
Platte
River
Basin
Study
Unit,
between
April
and
December
of
1993,
carbaryl
was
detected
in
14
urban
drainage
samples
and
6
agricultural
drainage
samples.
Carbaryl
had
the
highest
concentration
of
the
four
insecticides
analyzed
with
a
maximum
concentration
of
2.5
:
g/
L
in
the
urban
basin
and
1.5
:
g/
L
in
the
agricultural
basin
(http://
webserver.
cr.
usgs.
gov/
nawqa/
splt/
meetings/
KIMB1.
html).
In
the
South
Central
Texas
Study
Unit
carbaryl
was
detected
in
12%
of
streams
draining
agricultural
areas
and
52
%
draining
urban
areas
(Bush
et
al.,
2000)
http://
water.
usgs.
gov/
pubs/
circ/
circ1212/.
Registrant
Monitoring
Study
Aventis
Crop
Science
initiated
in
February
1999
a
surface
water
monitoring
study
of
carbaryl
residues
in
surface
water
in
areas
believed
to
have
high
agricultural
and
residential
use,
based
predominantly
on
county
level
sales
data.
A
total
of
20
sites
are
monitored,
with
"medium
sized
watersheds"
targeted:
16
sites
in
agricultural
areas
and
4
in
areas
draining
suburban
areas.
Samples
of
raw
water
were
collected
at
municipal
water
treatment
facilities.
When
raw
water
analyses
detected
carbaryl,
stored
finished
water
samples
(collected
at
the
same
time)
were
analyzed.
Samples
were
collected
weekly
during
periods
suspected
of
being
"high
risk"
and
monthly
the
rest
of
the
year
in
agricultural
areas.
Suburban
sites
were
sampled
weekly.
The
study
was
originally
envisioned
to
last
for
one
year,
but
was
extended
for
an
additional
year
in
February,
2000
(amendment
7),
and
for
a
third
year
in
February,
2001
(amendment
9).
Carbaryl
was
analyzed
by
HPLC/
MS/
MS
with
a
limit
of
detection
of
0.002
ppb
(2
ppt)
and
a
limit
of
quantitation
(LOQ)
of
0.030
ppb
(30
ppt).
OPP
has
received
two
interim
reports
of
monitoring
from
this
study.
The
first
report
(MRID
45116201)
has
been
fully
reviewed
and
results
are
described
below.
Very
recently
a
second
report
was
received
by
OPP/
EFED.
Results
from
this
latest
report
(MRID
45394101)
have
not
been
reviewed
in
depth,
but
are
similar
to
results
from
year
one.
Carbaryl
was
widely
detected
at
surface
water
sites
monitored
in
this
study.
Samples
containing
carbaryl
were
detected
in
raw
drinking
water
samples
collected
at
all
four
suburban
monitoring
locations,
and
at
about
three
quarters
of
the
agricultural
monitoring
locations
(13
of
16
sites).
Carbaryl
was
not
detected
as
frequently
in
finished
drinking
water
samples
when
they
were
analyzed;
however,
only
a
small
subset
of
finished
water
samples
were
actually
analyzed.
This
represents
a
significant
flaw
in
the
study
design
and
limited
its
usefulness
for
evaluating
the
effects
36
of
treatment.
Differences
in
concentrations
between
raw
and
finished
drinking
water
are
likely
attributed
more
to
changes
in
the
concentration
of
source
water
than
to
effects
of
treatment.
Most
carbaryl
detections
in
this
study
were
at
low
levels,
below
the
LOQ
of
0.03
ppb.
Carbaryl
contamination
measured
in
this
monitoring
study
appears
to
be
transient,
and
therefore
it
is
unlikely
that
any
but
the
most
intensive
field
sampling
would
ever
detect
the
actual
peak
concentration
that
occurs
at
a
site.
The
interim
study
reports
have
not
adequately
addressed
why
concentrations
found
in
this
study,
which
claims
to
target
high
carbaryl
use
areas,
are
substantially
lower
than
those
measured
in
the
untargeted
USGS
NAWQA
studies.
That,
and
the
limited
number
of
sites
sampled,
limit
the
usefulness
of
this
study.
Summary
of
year
one
monitoring
In
raw
water
samples
from
suburban
sites
detectable
residues
in
raw
water
ranged
from
0.002
to
0.023
ppb.
11
out
of
40
raw
water
samples
from
Sweetwater
Creek,
the
source
of
water
for
the
East
Port
facility
in
Douglas,
GA
had
detectable
levels
ranging
from
0.002
to
0.018
ppb.
One
out
of
46
samples
from
Joe
Pool
Lake,
Ellis
Texas
had
a
detection
at
0.014
ppb.
Jorden
Lake
in
Cary,
NC
had
2
detections
out
of
44
samples
(0.004
and
0.003
ppb).
11
out
of
40
samples
from
the
Cahaba
River
in
Birmingham
AL
had
detections
ranging
from
0.002
to
0.023
ppb.
Finished
water
sampled
from
suburban
areas
were
all
below
the
detection
limit.
In
samples
from
agricultural
sites
9
out
of
15
water
sources
had
some
detectable
level
of
carbaryl.
The
detections
were
generally
at
low
levels,
with
one
of
about
0.16
ppb
and
one
of
0.031.
The
rest
were
below
the
level
of
quantitation
(<
0.030
ppb).
Samples
from
finished
water
were
generally
lower
than
raw
water,
though
it
appears
that
raw
and
finished
water
sampling
did
not
sample
the
same
mass
of
water.
Therefore,
the
data
can
not
be
used
to
evaluate
the
effectiveness
of
water
treatment
on
carbaryl.
Because
the
samples
were
collected
at
the
same
time,
the
water
exiting
the
treatment
plant
was
temporally
different
than
the
water
entering
and
represent
different,
independent,
parcels
of
water.
In
several
cases
finished
water
had
higher
concentrations
than
raw
water,
and
finished
water
had
detectable
carbaryl
when
the
raw
did
not.
The
highest
concentration
measured
was
in
finished
water
(0.18
ppb).
Raw
water
sampled
at
the
same
time
had
much
lower
concentration
(0.010).
Non
targeted
monitoring,
such
as
the
NAWQA
program,
has
shown
that
much
higher
concentrations
occur
indicating
that
this
study,
while
useful,
can
not
be
used
to
describe
the
overall
distribution
of
concentrations
that
occur
throughout
the
entire
use
area.
This
study
does
not
provide
sufficient
information
to
allow
estimation
of
actual
peak
and
mean
concentrations
that
actually
occur
in
all
use
areas.
The
highest
concentration
values
measured
in
this
study
are
close
to
the
average
values
seen
in
other,
non
targeted,
studies.
Only
limited
information
was
submitted
on
sampling
site
selection
and
how
the
sites
relate
to
the
overall
distribution
of
use
areas.
Home
and
garden
sites
were
selected
downstream
of
urban/
suburban
areas
that
were
believed
to
have
high
use
based
on
county
scale
sales
data.
37
Agricultural
sites
were
selected
based
on
county
scale
sales
data,
and
are
believed
to
be
in
"major
use
counties."
This
study
is
still
ongoing
and
only
interim
study
results
have
been
submitted.
Additional
information
is
needed
to
evaluate
the
study
results.
Additionally,
an
analysis
of
how
the
selected
sites
relate
to
the
nationwide
distribution
of
carbaryl
use
areas
is
required.
This
should
include
an
explanation
of
why
this
study
did
not
observe
concentrations
as
high
as
those
found
in
other,
nontargeted
studies,
and
how
the
results
of
this
study
can
be
related
to
concentrations
that
occur
throughout
the
country.
Based
on
the
interim
data
submitted
it
appears
that
this
study
measured
concentrations
similar
to
those
observed
in
non
targeted
studies
but
did
not
capture
high
end
or
peak
values.
Until
additional
information
is
submitted
it
is
not
possible
to
use
these
interim
results
for
more
then
to
reinforce
the
inferences
drawn
from
non
targeted
study
data.
Sacramento
San
Joaquin
River
Delta
As
part
of
a
two
year
study
into
the
cause
of
declines
in
aquatic
insects
in
California's
Sacramento
San
Joaquin
Delta,
toxicity
of
surface
water
was
measured
using
ceriodaphnia.
When
toxicity
was
found,
toxic
identification
evaluation
was
done
to
determine
the
causative
agent.
Carbaryl
was
found
to
be
the
primary
toxicant
at
one
of
20
sites
sampled
in
1995,
with
concentration
of
7.0
:
g/
L.
The
toxicity
seemed
to
persist
for
several
days
(Werner,
et
al.,
2000).
STORET
The
EPA
STORET
database
(
was
queried
on
May
12,
1999
for
reports
of
measurements
of
carbaryl
in
surface
water.
The
database
contained
8048
records
indicating
that
analysis
was
done
for
carbaryl.
Out
of
these
432
reported
concentrations
above
the
detection
limits.
The
maximum
value
reported
was
5.5
µg/
L.
Of
the
reported
detections
18
were
above
1
ppb.
The
data
is
the
STORET
database
is
used
to
give
a
general
indication
of
the
occurrence
pattern
only.
Lack
of
QA/
QC
and
analytical
methodology
limitations
limit
the
usefulness
of
the
STORET
data.
However,
reported
detections
of
carbaryl
suggest
that
the
compound
is
infrequently
detected
in
surface
water
and
at
low
levels.
6.0
Hazard
and
Risk
Assessment
for
Aquatic
Organisms
Hazard
Assessment
for
Aquatic
Organisms
Freshwater
Fish
On
an
acute
basis,
technical
carbaryl
is
moderately
to
highly
toxic
to
freshwater
fish
and
to
fish
that
spend
a
portion
of
their
life
cycle
in
fresh
water,
such
as
the
Atlantic
salmon
(LC50
=
0.25
20
ppm).
LC50
values
for
the
typical
end
use
products
range
from
1.4
to
290
ppm,
falling
in
the
moderately
to
practically
nontoxic
categories.
Calculation
of
acute
and
chronic
risk
quotients
for
freshwater
fish
are
based
on
an
Atlantic
salmon
LC50
of
250
ppb
and
a
fathead
minnow
NOAEC
of
210
ppb,
respectively.
38
Amphibians
According
to
an
available
supplemental
study
with
a
50%
carbaryl
formulation,
the
LD50
for
the
bullfrog
(Rana
catesbeiana)
is
greater
than
4,000
mg/
kg,
or
practically
nontoxic
(MRID
00160000).
A
single
acute
exposure
of
plains
leopard
frog
tadpoles
(Rana
blairi)
to
carbaryl
concentrations
in
the
3.5
7.2
mg/
L
range
led
to
a
90%
reduction
in
swimming
activity,
including
sprint
speed
and
sprint
distance,
activity
ceasing
completely
at
7.2
mg/
L
(Bridges
1997).
This
reduction
in
activity
and
swimming
performance
may
result
in
increased
predation
rates
and,
because
activity
is
closely
associated
with
feeding,
may
result
in
slowed
growth
that
could
lead
to
failure
to
complete
metamorphosis.
Acute
exposure
to
low
carbaryl
levels
may
not
only
affect
immediate
survival
of
tadpoles
but
also
impact
critical
life
history
functions.
On
a
chronic
basis,
carbaryl
has
been
shown
to
have
the
potential
to
adversely
affect
amphibians.
In
a
recent
study,
nearly
18%
of
southern
leopard
frog
(Rana
sphenocephala)
tadpoles
exposed
to
carbaryl
during
development
exhibited
some
type
of
developmental
deformity,
including
both
visceral
and
limb
malformations,
compared
to
a
single
deformed
(<
1%)
control
tadpole
demonstrating
that
carbaryl
exposure
can
result
in
amphibian
deformities
(Bridges,
2000).
Although
the
length
of
the
larval
period
was
the
same
for
all
experimental
groups,
tadpoles
exposed
throughout
the
egg
stage
were
smaller
than
their
corresponding
controls.
Because
exposure
to
nonpersistent
chemicals
may
last
for
only
a
short
period
of
time,
it
is
important
to
examine
the
long
term
effects
that
short
term
exposure
has
on
larval
amphibians
and
the
existence
of
any
sensitive
life
stage.
Any
delay
in
metamorphosis
or
decrease
in
size
at
metamorphosis
can
impact
demographic
processes
of
the
population,
potentially
leading
to
declines
or
local
extinction.
Freshwater
Invertebrates
Carbaryl
is
very
highly
toxic
to
aquatic
invertebrates
(1.7
26
ppb)
on
an
acute
basis.
This
compound
also
has
a
very
strong
potential
for
chronic
effects
to
invertebrates
(NOAEC
=
3.3
ppb).
Field
studies
that
evaluated
populations
of
damselflies
(Xanthocnemis
zealandica)
after
exposure
to
100
µg/
L
carbaryl
showed
a
90%
reduction
in
emergence
success
after
10
12
days
exposure
(Hardersen
and
Wratten,
1998).
Studying
natural
plankton
communities
in
enclosed
mesocosms,
Havens
(1995)
reports
a
decline
in
total
zooplankton
biomass
and
individuals
across
the
range
of
carbaryl
treatments
(0
100
ug/
L).
Furthermore,
at
carbaryl
concentrations
greater
than
20
µg/
L
Daphnia
was
no
longer
found
and
that
at
concentrations
above
50
ug/
L
all
cladocerans
were
eliminated,
resulting
in
an
increase
in
algal
biomass,
representing
a
repartitioning
of
biomass
from
zooplankton
to
phytoplankton.
Hanazato
(1995)
exposed
Daphnia
ambigua
to
carbaryl
and
a
kairomone
released
by
the
predator
Chaoborus
(phantom
midge)
simultaneously.
Daphnia
developed
helmets
in
response
to
the
kairomone,
but
not
in
response
to
carbaryl
at
1
3
µg/
L.
However,
carbaryl
enhanced
the
development
of
high
helmets
and
prolonged
the
maintenance
period
of
the
helmets
in
the
presence
of
the
kairomone,
suggesting
that
at
low
concentrations
carbaryl
can
alter
predator
prey
interactions
by
inducing
helmet
formation
and
vulnerability
to
predation
in
Daphnia.
In
related
mesocosms
studies,
exposure
to
carbaryl
at
1
ppm
killed
all
plankton
species,
including
Chaoborus
larvae
(Hanazato,
1989).
However,
this
concentration
is
well
above
the
maximum
EECs
modeled
for
carbaryl,
and
is
unlikely
that
such
high
levels
of
this
chemical
would
39
be
found
under
field
conditions.
Mora
et
al.
(2000)
studying
the
relationship
between
toxicokinetics
of
carbaryl
and
effects
on
acetylcholinesterase
(ACHase)
activity
in
the
snail,
Pomaca
patula,
observed
increased
enzyme
inhibition,
along
with
the
bioconcentration
of
carbaryl,
after
72
hours
of
exposure
to
sublethal
levels
(3.2
ug/
g).
The
transfer
of
snails
to
carbaryl
free
water
was
followed
by
rapid
monophasic
elimination
with
a
half
life
of
1.0
hour,
although
ACHase
activity
levels
never
returned
to
control
values.
The
risk
assessment
for
freshwater
invertebrates
is
based
on
a
stonefly
LC50
of
1.7
ppb
and
a
water
flea
NOAEC
of
1.5
ppb,
respectively.
Estuarine/
Marine
Fish
Carbaryl
is
categorized
as
moderately
toxic
to
estuarine/
marine
fish
on
an
acute
basis,
based
on
a
minnow
LC50
of
2.6
ppm.
Laboratory
exposure
to
a
single
dose
of
carbaryl
at
100
ppb
can
adversely
affect
schooling
behavior
in
the
silverside
(Weis
and
Weis,
1974).
Exposure
to
carbaryl
at
10
ppb
caused
retardation
of
fin
regeneration
during
the
first
week
of
the
study
in
the
killifish
(Fundulus
heteroclitus)
(Weis
and
Weis
1975).
Field
exposure
to
a
maximum
carbaryl
water
concentration
of
1.2
ppm
affected
burying
behavior
in
caged
English
sole
young
(Pozorycki,
1999).
The
acute
risk
assessment
for
estuarine/
marine
fish
is
based
on
a
sheepshead
minnow
LC50
of
2.6
ppm.
At
present,
the
chronic
NOAEC
for
marine/
estuarine
fish
has
not
been
established,
therefore
additional
chronic
toxicity
studies
are
required.
Guideline
72
4(
a)
is
not
fulfilled.
Estuarine/
Marine
Invertebrates
Technical
carbaryl
is
categorized
as
very
highly
toxic
to
estuarine/
marine
shrimp
species
and
moderately
toxic
to
oysters
on
an
acute
basis.
The
mysid
LC50
falls
in
the
5.7
9.6
ppb
range
and
the
oyster
LC50
is
2.7
ppm.
Typical
end
use
carbaryl
products
are
considered
very
highly
toxic
to
mysids
and
slightly
toxic
to
oysters.
Carbaryl
applied
to
oyster
beds
in
Washington
State
tidelands
at
7.5
8
lb
ai/
acre
to
control
ghost
and
mud
shrimp
has
been
shown
to
be
lethal
to
many
nontarget
invertebrate
species.
The
acute
risk
assessment
for
estuarine/
marine
invertebrates
is
based
on
a
mysid
LC50
of
5.7
ppb.
There
is
insufficient
data
to
assess
the
chronic
risk
for
estuarine/
marine
invertebrates.
Additional
chronic
toxicity
studies
are
required.
Guideline
72
4(
b)
is
not
fulfilled.
40
Aquatic
Plants
Data
based
on
a
single
available
core
toxicity
study
with
the
green
alga
Pseudokirchneria
subcapitata
(formerly
Selenastrum
capricornutum)
indicates
that
the
LC50
and
NOAEC
are,
respectively,
1.1
ppm
and
0.37
ppm
.
Toxicity
testing
for
the
following
four
aquatic
plants
is
required
to
support
carbaryl's
registered
forestry
uses;
duckweed
(Lemna
gibba),
marine
diatom
(Skeletonema
costatum),
freshwater
blue
green
algae
(Anabaena
flos
aquae),
and
a
freshwater
diatom.
Guideline
122
2
is
not
fulfilled.
1
Naphthol
1
naphthol,
the
major
metabolite
of
carbaryl
degradation
by
abiotic
and
microbially
mediated
processes
is
moderately
to
highly
toxic
to
aquatic
organisms
on
an
acute
basis.
LC50
values
range
from
0.75
to
1.6
ppm
for
freshwater
fish,
from
1.2
to
1.8
ppm
for
estuarine/
marine
fish,
from
0.70
to
0.73
ppm
for
freshwater
invertebrates,
and
from
0.21
to
2.5
ppm
for
estuarine/
marine
invertebrates.
Risk
Assessment
for
Aquatic
Organisms
A
detailed
analyses
of
risk
quotients
(RQs)
in
relation
to
their
corresponding
levels
of
concern
(LOCs)
is
presented
in
Appendix
B.
A
summary
of
the
acute
and
chronic
LOC
exceedances
for
aquatic
organisms,
based
on
maximum
label
rates,
is
presented
in
Tables
7
and
8.
Freshwater
Fish
Carbaryl
is
highly
to
slightly
toxic
to
freshwater
fish
(LC50
=
0.25
20
ppm)
on
an
acute
basis.
The
acute
risk
LOC
(0.5)
for
freshwater
fish
is
exceeded
for
one
of
five
use
scenarios
modeled
(citrus),
at
maximum
label
(RQ:
1.10),
"average"
(RQ:
0.58),
and
maximum
reported
(RQ:
0.93)
use
rates,
and
not
exceeded
for
the
other
four
scenarios
(sweet
corn,
field
corn,
apples,
sugar
beets).
The
chronic
risk
LOC
is
not
exceeded
for
any
of
the
five
use
scenarios
modeled
(Table
7).
These
data
suggest
that
carbaryl
uses
may
present
a
risk
to
freshwater
fish
only
under
situations
that
combine
high
application
rates
and
runoff
into
water
bodies,
such
as
ponds
or
lagoons,
where
the
chemical
may
reach
toxic
levels.
Sublethal
effects
have
been
documented
in
the
literature
showing
that
in
fish
the
inhibition
of
acetycholinesterase
(AChE)
can
effect
thyroid
and
gonadal
dysfunction
in
the
freshwater
murrell,
Channa
punctatus,
resulting
in
ACh
accumulation.
At
the
0.21
ppm
concentration
level
carbaryl
was
found
to
reduce
pituitary
and
serum
gonadotropin
levels
accompanied
by
inhibition
of
hypothalamic
gonadotropin
releasing
hormone
(GnRH)
(Bhattacharya,
1993).
These
test
concentration
are
at
the
upper
end
of
the
water
EECs
modeled
for
carbaryl
(citrus
scenario).
41
Freshwater
Aquatic
Invertebrates
Acute
and
chronic
risk
LOCs
are
exceeded
for
freshwater
invertebrates
for
all
five
carbaryl
use
aquatic
scenarios
modeled
using
maximum
label
use
rates
(acute
RQs
=
5.06
161.18,
chronic
RQs
=
3.27
91.33),
maximum
reported
rates
(acute
RQs
=
3.30
136.47,
chronic
RQs
=
2.00
74.67
and
"average"
rates
(acute
RQs
=
2.65
85.29,
chronic
RQs
=
1.67
44.67),
indicating
that
most
carbaryl
uses
are
likely
to
pose
acute
and
chronic
risks
to
freshwater
invertebrates,
especially
to
arthropods.
Although
carbamates
and
OP's
breakdown
rapidly
in
the
environment,
studies
pertaining
to
agricultural
regions
where
these
insecticides
are
applied
for
extended
periods
of
the
year
have
shown
that
nontarget
aquatic
invertebrates
may
be
exposed
to
high
levels
of
ChE
inhibiting
compounds
for
a
period
of
up
to
several
months
(Gruber
and
Munn,
1998).
In
general,
due
to
its
rapid
metabolism
and
rapid
degradation,
carbaryl
should
not
pose
a
significant
bioaccumulation.
Table
7.
Summary
of
acute
and
chronic
risk
LOC
exceedances,
based
on
maximum
label
application
rates,
for
freshwater
organisms
1
Organism
Use
site
Scenarios
Risk
Quotients
Equal
or
Exceed
Level
of
Concern
for:
Acute
Risk
(RQs)
Acute
Restricted
Use
Acute
Endangered
Species
Chronic
Risk
Fish
Sweet
Corn
NO
YES
YES
NO
Field
Corn
NO
YES
YES
NO
Apples
NO
NO
NO
NO
Sugar
Beets
NO
NO
YES
NO
Citrus
YES
(1.1)
YES
YES
NO
Aquatic
Invertebrates
Sweet
Corn
YES
(27.1)
YES
YES
YES
(17.3)
Field
Corn
YES
(16.5)
YES
YES
YES
(10.7)
Apples
YES
(5.
1)
YES
YES
YES
(3.
3)
Sugar
Beets
YES
(11.2)
YES
YES
YES
(7.3)
Citrus
YES
(161.2)
YES
YES
YES
(91.3)
1
Levels
of
concern
(LOCs)
for
aquatic
organisms
Acute
Risk
0.5
Acute
Restricted
Use
0.
1
Acute
Endangered
species
0.05
Chronic
Risk
1
Estuarine/
Marine
Fish
Carbaryl
is
moderately
toxic
to
estuarine/
marine
fish
(LC50
=
2.6
ppm);
however,
no
acute
LOCs
are
exceeded
for
any
of
the
five
use
scenarios
modeled,
at
any
use
rate
(Table
8).
Thus,
most
carbaryl
uses
are
unlikely
to
pose
an
acute
risk
to
marine/
estuarine
fish.
Although
a
NOAEC
based
on
core
data
has
not
been
established,
evidence
from
the
open
literature
indicates
that
exposure
to
5
Also
referred
in
the
literature
as
Callianassa
californiensis.
42
low
carbaryl
levels
may
produce
adverse
physiological
and
behavioral
effects
in
estuarine/
marine
fish.
Laboratory
exposure
of
Menidia
menidia
to
a
single
dose
of
carbaryl
(100
ppb)
resulted
in
the
disruption
of
schooling
behavior,
as
carbaryl
exposed
groups
consistently
occupied
twice
the
space
of
control
groups,
which
was
attributed
to
the
accumulation
of
the
carbaryl
degradate
1
naphthol
(Weis
and
Weis,
1974).
Exposing
the
killifish
(Fundulus
heteroclitus)
to
carbaryl
at
10
ppb
in
the
laboratory
caused
retardation
of
fin
regeneration
during
the
first
week
of
the
study
(Weis
and
Weis
1975).
According
to
Pozorycki
(1999),
field
studies
with
caged
juvenile
English
sole
(Pleuronectes
vetulus)
indicated
that
brain
acetylcholinesterase
(AChE)
activity
decreases
following
carbaryl
application,
affecting
the
ability
to
bury
in
sediments.
Mean
brain
AChE
inhibition
was
26%
in
fish
placed
on
treated
mudflats
and
24%
in
fish
placed
subtidally,
but
maximum
individual
values
approached
50%.
AChE
inhibition
at
50
60%
was
noted
as
a
threshold
value
below
which
burying
decreased
sharply.
Maximum
carbaryl
water
concentration
measured
by
HPLC
was
1.2
µg/
ml
at
the
cage
sites.
Sediment
concentrations
on
treated
mudflats
were
as
high
as
23
µg/
g
24
hrs
after
application.
Chronic
toxicity
studies
with
an
estuarine/
marine
fish
species
is
required.
There
is
one
carbaryl
use
in
particular
that
represents
a
potential
acute
and
chronic
risk
to
estuarine/
marine
fish.
Since
1963,
carbaryl
has
been
used
to
treat
two
tideland
areas
of
Washington
State
for
the
control
of
two
species
of
burrowing
shrimp
in
commercial
oyster
beds.
The
acute
risk
to
fish
inhabiting
treated
mudflats
or
trapped
in
shallow
pools
is
extremely
high,
often
resulting
in
fish
kills.
Exposure
to
sublethal
carbaryl
levels
has
also
been
shown
to
inhibit
acetylcholinesterase
in
fish
in
subtidal
areas
adjacent
to
the
treated
sites
resulting
in
a
significant,
although
reversible,
impairment
of
burying
behavior,
thus
increasing
their
exposure
to
predators.
Carbaryl
is
applied
aerially,
at
the
rate
of
7.5
8
lb
ai/
acre
(maximum
label
rate)
over
oyster
seed
beds
and
bare
mudflats
on
a
combined
total
of
800
acres
of
tidelands
in
Willapa
Bay
and
Grays
Harbor,
Washington,
to
control
burrowing
shrimp
populations
(Neotrypaea
5
californiensis
and
Upogebia
pugettensis).
Applications
are
made
when
shrimp
population
densities
meet
the
established
action
threshold
of
10
burrow
holes
per
square
meter.
On
average,
oyster
beds
are
treated
once
every
six
years
(Feldman
et
al.
2000).
Unchecked,
these
shrimp
can
adversely
affect
oyster
production
by
making
the
substrate
unsuitable
for
oyster
culture
and
by
competing
with
these
bivalves
for
food
resources
(Hulburt
et
al.
1989).
43
Table
8.
Summary
of
acute
risk
LOC
exceedances,
based
on
maximum
label
application
rates,
for
marine/
estuarine
organisms
1
Organism
Use
site
Scenarios
Risk
Quotients
Equal
or
Exceed
Level
of
Concern
for:
Acute
Risk
(RQs)
Acute
Restricted
Use
Acute
Endangered
Species
Chronic
Risk
Fish
Sweet
Corn
NO
NO
NO
No
Data
Field
Corn
NO
NO
NO
No
Data
Apples
NO
NO
NO
No
Data
Sugar
Beets
NO
NO
NO
No
Data
Citrus
NO
YES
YES
No
Data
Aquatic
Invertebrates
Sweet
Corn
YES
(27.1)
YES
YES
No
Data
Field
Corn
YES
(16.5)
YES
YES
No
Data
Apples
YES
(5.1)
YES
YES
No
Data
Sugar
Beets
YES
(11.2)
YES
YES
No
Data
Citrus
YES
(161.2)
YES
YES
No
Data
1
Levels
of
concern
(LOCs)
for
aquatic
organisms
Acute
Risk
0.5
Acute
Restricted
Use
0.
1
Acute
Endangered
species
0.05
Chronic
Risk
1
In
addition
to
providing
a
substantial
portion
of
U.
S.
oyster
production,
these
estuaries
are
also
important
nurseries
for
several
valuable
fisheries.
Estimates
of
potential
fish
kills
in
the
treated
area
range
from
15,000
to
96,000.
Species
killed
following
carbaryl
applications
include
staghorn
sculpin
(Leptocottus
armatus),
saddleback
gunnels
(Pholis
ornata),
English
and
sand
sole
(Parophrys
vetulus
and
Psettichthys
melanostictus),
shiner
perch
(Cymatogaster
aggregata),
starry
flounder
(Platichthys
stellatus),
bay
gobies
(Lepidogobius
lepidus),
and
three
spine
sticklebacks
(Gasterosteus
aculeatus)
(Feldman
2001).
Furthermore,
fish
inhabiting
subtidal
channels
or
migrating
over
treated
mudflats
with
the
flood
tide
may
exhibit
a
marked
reduction
in
brain
acetylcholinesterase
(AChE)
activity.
Field
studies
with
caged
juvenile
English
sole
(Pleuronectes
vetulus)
indicated
that
mean
brain
AChE
inhibition
was
26%
in
fish
placed
on
treated
mudflats
and
24%
in
fish
placed
subtidally,
maximum
individual
values
approaching
50%.
The
maximum
carbaryl
water
concentration
was
1.2
ppm
at
the
cage
sites,
while
sediment
concentrations
on
treated
mudflats
were
as
high
as
23
ppm
24
hours
following
application.
In
treated
mudflats,
invertebrates
that
are
a
source
of
food
for
these
fish
had
carbaryl
concentrations
as
high
as
76
ppm.
It
was
estimated
that
AChE
inhibition
of
up
to
50%
was
possible
due
to
the
additive
exposure
to
carbaryl
in
water
and
prey
items,
resulting
in
temporary
impairment
of
burying
behavior
and
increased
exposure
to
predators
(Hulburt
et
al.
1989).
Recovery
of
burying
behavior
occurred
after
removal
of
the
exposure.
Several
potential
nonchemical
pest
management
methods
have
been
identified,
including
alternative
culture
techniques,
mechanical
control,
enhancement
of
shrimp
predators,
electrofishing,
44
and
modification
of
carbaryl
application.
Results
have
shown
significant
short
term
impacts
to
arthropods
on
a
species
specific
basis
(Brooks,
1993).
Additional
mitigation
measures
may
include
alternative
carbaryl
application
techniques
that
reduce
dispersion
to
nontarget
areas,
such
as
direct
injection
of
carbaryl
into
the
sediment.
Subsurface
injection
has
shown
to
be
effective
in
controlling
burrowing
shrimp
and
uses
66%
less
chemical
than
aerial
application
(Durfey
and
Simpson,
1995).
Applying
a
layer
of
oyster
shells
(shell
pavement)
is
a
promising
technique
that
can
reduce
ghost
shrimp
densities
under
certain
conditions,
but
this
approach
can
be
disruptive
to
the
oyster
culture
and
remains
untested
on
a
commercial
scale.
To
date,
the
complexity
of
the
oyster
culture
and
the
ecology
of
the
burrowing
shrimp
has
disrupted
attempts
to
develop
and
adopt
practical
and
costeffective
alternative
control
methods
(Feldman
et
al.,
2000).
Estuarine/
Marine
Invertebrates
The
acute
LOC
for
estuarine/
marine
invertebrates
is
exceeded
for
all
five
carbaryl
use
scenarios
assessed
at
maximum
label
application
rates
(acute
RQs
=
1.51
48.07),
at
maximum
reported
use
rates
(acute
RQs
=
1.05
40.70),
and
at
"average"
rates
(acute
RQs
=
0.79
25.44)
indicating
that
some
carbaryl
uses
may
pose
an
acute
risk
to
estuarine/
marine
invertebrates
inhabiting
intertidal
zones
and
estuaries
located
downstream
from
treated
areas.
It
is
not
possible
to
evaluate
chronic
risk
to
estuarine/
marine
invertebrates
at
this
time
due
to
the
unavailability
of
data.
As
for
fish,
carbaryl
applications
to
control
burrowing
shrimp
in
Washington
State
tidelands
is
known
to
represent
a
significant
acute
risk
to
estuarine/
marine
invertebrates
inhabiting
treated
tideland
areas.
There
may
be
up
to
100%
mortality
of
Dungenese
crab
(Cancer
magister)
populations
following
carbaryl
applications
(Hulburt
et
al.
1989).
In
addition,
the
populations
of
some
salmonid
arthropod
prey
species
are
significantly
reduced
following
application,
while
other
species
are
more
tolerant.
Most
populations
recover
within
51
days,
but
some
do
not
recover
(Brooks
1993).
Once
established,
oyster
beds
do
provide
an
enhanced
environment
for
many
plants
and
invertebrates
that
grow
on
the
oyster
shells
or
in
between
them,
and
which
are
normally
rare
or
absent
in
barren
mudflats.
Reproduction
Effects
on
Fish
There
is
information
indicating
that
carbaryl
has
the
potential
to
adversely
affect
reproduction
in
fish.
Carlson
(1972)
reports
that
when
the
fathead
minnow
(Primephales
promelas)
was
exposed
to
5
concentrations
of
carbaryl
in
the
0.008
0.68
mg/
l
range
for
9
months
and
throughout
a
life
cycle,
the
0.68
mg/
l
(680
ppb)
concentration
prevented
reproduction
and
decreased
survival.
At
this
high
concentration,
the
mean
number
of
eggs
per
female
and
the
mean
number
of
eggs
per
spawning
were
significantly
less
than
for
the
control
group,
and
no
hatching
occurred.
In
addition,
the
ovaries
contained
flaccid
eggs
and
appeared
to
be
in
a
resorptive
state.
However,
this
test
concentration
is
higher
than
the
highest
peak
EECs
derived
from
PRZM/
EXAMS,
and
it
is
therefore
unlikely
that
fish
will
be
exposed
to
such
high
carbaryl
levels
for
extended
periods
under
field
conditions.
45
Ghosh
et
al.
(1990)
report
that
serum
and
pituitary
levels
of
gonadotropic
hormone
(GtH)
and
gonadotropin
releasing
hormone
(GnRH)
in
C.
punctatus
were
significantly
reduced
by
exposure
to
nonlethal
levels
(1.66
3.73
ppm)
of
carbaryl
in
laboratory
and
paddy
field
tests,
indicating
that
at
these
doses
carbaryl
may
cause
reproductive
effects
to
fish.
It
must
be
pointed
out,
however,
that
the
test
doses
selected
for
this
study
are
one
order
of
magnitude
higher
than
the
highest
peak
concentrations
derived
from
PRZM/
EXAMS
modeling.
The
decrease
in
GnRH
levels
could
indicate
constant
exposure
to
elevated
levels
of
estrogen
acting
through
a
negative
feedback
pathway
to
inhibit
GnRH
release,
and
the
subsequent
release
of
gonadotropins
(Klotz
et
al.
1997).
In
a
related
study,
freshwater
perch
(Anabas
testudineus)
were
exposed
to
nonlethal
carbaryl
levels
(1.66
ppm)
for
90
days,
covering
the
pre
spawning
and
spawning
phases
of
the
annual
reproductive
cycle.
Plasma
and
ovarian
estrogen
levels
in
treated
fish
increased
significantly
until
day
15,
after
which
they
declined
significantly
relative
to
the
control,
until
the
end
of
the
experiment,
indicating
that
at
short
term
exposures
nonlethal
levels
of
carbaryl
have
no
inhibitory
effect,
while
long
term
exposure
has
an
inhibitory
effect
on
fish
reproduction
(Choudhury
et
al.
1993).
However,
this
study
was
also
performed
at
carbaryl
concentrations
well
above
the
highest
concentration
modeled
for
carbaryl
(Table
5)
and,
therefore,
does
not
provide
an
indication
as
to
potential
effects
under
field
conditions.
Endangered
Aquatic
Species
The
endangered
species
level
of
concern
for
freshwater
fish
is
exceeded
for
three
(sweet
corn,
field
corn,
and
citrus)
of
five
use
scenarios
modeled
and
for
the
citrus
scenario
at
less
than
maximum
label
rates.
For
marine/
estuarine
fish,
the
endangered
species
LOC
is
met
for
the
citrus
scenario
only
at
maximum
label
rates.
The
endangered
species
LOC
is
exceeded
for
freshwater
and
marine/
estuarine
aquatic
invertebrates
for
all
five
use
scenarios
at
maximum
label,
maximum
reported,
and
"average"
application
rates.
7.0
Hazard
and
Risk
Assessment
for
Terrestrial
Organisms
Hazard
Assessment
for
Terrestrial
Organisms
Avian
Carbaryl
is
slightly
toxic
to
practically
nontoxic
to
avian
species
on
an
acute
basis.
LD50
values
are
greater
than
2,000
mg/
kg
in
pheasants,
greater
than
2,564
mg/
kg
in
mallards,
and
fall
in
the
1,000
1,790
mg/
kg
range
for
a
passerine
species
(rock
doves).
LD50
values
as
low
as
16.2
mg/
kg
and
56.2
mg/
kg,
based
on
simple
screening
tests,
have
been
reported
for
the
starling
and
the
red
winged
blackbird,
respectively
(Schafer
et
al.,
1983).
At
a
subacute
level,
carbaryl
is
categorized
as
practically
nontoxic
to
birds,
with
LC50
values
greater
than
5,000
ppm.
However,
chronic
reproduction
effects
(egg
production)
from
carbaryl
exposure
have
been
noted
in
the
mallard
duck
at
the
1000
and
3000
ppm
levels
(LOAEC
=
1000
ppm,
NOAEC
=
300
ppm).
Other
reproduction
effects,
at
the
3000
ppm
level,
include
cracked
eggs,
fertility,
embryonic
mortality,
and
hatching
success.
46
According
to
DeRosa
et
al.
(1976),
significant
amounts
of
carbaryl
were
detected
in
the
egg
yolks
of
adult
Coturnix
quail
(Coturnix
coturnix
japonica)
following
pesticide
ingestion,
with
treatment
levels
of
20,
40,
and
400
ppm
resulting
in
pesticide
residues
of
1.58,
2.03,
and
3.15
ppm,
respectively
in
the
egg
yolk.
In
addition,
egg
production
was
significantly
reduced,
although
egg
viability
was
not
affected,
and
agonistic
behavior
decreased
in
males,
while
increasing
in
the
females.
The
rock
dove
acute
oral
LD50
of
1000
mg/
kg
is
used
to
assess
risk
for
granular
uses,
whereas
the
quail
subacute
dietary
LD50
of
>5000
ppm
and
the
mallard
duck
reproduction
NOAEC
of
300
ppm
are
used
to
assess,
respectively,
acute
and
chronic
risk
for
nongranular
uses.
Mammalian
With
a
rat
LD50
of
301
mg/
kg,
carbaryl
is
categorized
as
moderately
toxic
to
small
mammals
on
an
acute
oral
basis.
However,
NOAEC
and
LOAEC
values
of
80
and
600
ppm,
respectively,
based
on
decreased
fetal
body
weights
and
increased
incomplete
ossification
of
multiple
bones
in
the
laboratory
rat
suggest
that
carbaryl
has
the
potential
for
chronic
effects
on
small
mammals.
The
rat
LD50
of
301
mg/
kg
and
a
rat
NOAEC
of
80
ppm
are
the
toxicity
endpoints
used
in
the
risk
assessment
for
carbaryl.
Insects
Technical
carbaryl
is
highly
toxic
to
bees
on
an
acute
contact
basis
(LD50
=
1.3
µg/
bee).
The
topical
LD50
for
alfalfa
leaf
cutter
bee
(Megachile
pacifica
=
M.
rotundata)
is
262.4
µg/
g
(MRID
05015678:
Lee
&
Brindley,
1974).
Nongranular
carbaryl
formulations
can
be
highly
toxic
to
bees
exposed
to
direct
application,
i.
e.
when
bees
are
actively
visiting
blooming
crops
or
weeds.
Residual
toxicity
varies
with
the
crops
and
weather
conditions.
Exposing
leafcutting
bees
(Megachilidae),
alkali
bees
(Halictidae),
and
honey
bees
(Apidae)
to
24
hr
residues
from
80%
WP
carbaryl
applied
at
the
rate
of
1
lb/
acre
resulted,
respectively,
in
a
85%,
78%,
and
69%
mortality
rate
(Johansen
1972).
Carbaryl
is
also
moderately
to
highly
toxic
to
predaceous
arthropods,
including
lace
bugs
(Nabidae)
(MRID
05010807),
big
eyed
bugs
(Geocoridae:
Geocoris)
(MRID
05010807),
lady
beetles
(Coccinellidae:
Coccinella,
Cryptolaemus,
Hippodamia,
Lindorus,
Rhodolia,
Stethorus)
(MRIDs
05013372,
05003978,
05005640),
ground
beetles
(Carabidae:
Scarites,
Pterostichus,
Bembidion,
Harpalus)
(MRID
05008149),
hymenopterous
parasitoids
(Aphytis,
Metaphycus,
Spalangia,
Leptomastix)
(MRID
05003978,
05005640),
predaceous
mites
(Amblyseius,
Typhlodromus)
(MRIDs
05004148,
05013359,
05009346),
and
spiders
(MRID
05010807).
In
laboratory
tests,
field
weathered
carbaryl
residues
have
been
shown
to
kill
the
parasitic
wasp
Aphytis
holoxanthus,
a
natural
enemy
of
the
Florida
red
scale,
for
a
period
of
up
to
22
days
post
treatment
under
spring
conditions
in
Florida
(Rehman
et
al.,
1999).
Terrestrial
Plants
47
Although
carbaryl
is
primarily
an
insecticide,
it
can
also
be
used
as
a
fruit
thinning
agent
on
apples
and
pears.
However,
the
product's
label
cautions
that
if
applied
to
wet
foliage
or
during
periods
of
high
humidity,
it
may
cause
injury
to
tender
foliage.
The
label
also
cautions
against
using
carbaryl
on
Boston
ivy,
Virginia
creeper,
or
maidenhair
fern
due
to
potential
injury.
Several
incidents
involving
injury
to
vegetable
crops
(potatoes,
tomatoes,
cabbage,
and
broccoli)
in
New
York
and
Pennsylvania
have
been
reported.
Tier
I
and,
if
appropriate,
Tier
II
Seed
Germination
and
Seedling
Emergence,
as
well
as
Vegetative
Vigor
studies
are
required.
Risk
Assessment
for
Terrestrial
Organisms
To
assess
acute
risk
to
birds
from
exposure
to
nongranular
carbaryl,
estimated
environmental
concentrations
(EECs)
in
food
items
following
product
application
were
compared
to
LC50
values.
EECs
were
calculated
using
three
separate
sets
of
usage
data:
maximum
label
use
rates,
maximum
reported
(based
on
Doane
usage
data
available
for
42
uses)
use
rates,
and
"average"
use
rates
(used
mainly
for
comparison
purposes).
To
assess
chronic
risk
to
birds,
EECs
were
compared
to
NOAEC
values.
To
assess
acute
risk
to
birds
from
exposure
to
granular
carbaryl,
the
number
of
LD50
values
per
square
foot
was
used
as
the
risk
quotient
for
birds
in
three
separate
weight
classes
(20,
180,
and
1000
g).
Acute
risk
to
mammals
(herbivores/
insectivores
and
granivores)
from
exposure
to
nongranular
carbaryl
was
assessed
for
three
separate
body
weight
and
food
consumption
classes
(15g,
35g,
and
1000
g
mammals
and
daily
food
consumption
rates
equal
to
95%,
66%,
and
15%
of
their
body
weight,
respectively)
by
comparing
EECs
in
food
items
following
product
application
to
LD50
values.
Chronic
risk
to
mammals
was
assessed
for
the
same
three
weight
classes
by
comparing
EECs
to
NOAEC
values.
To
assess
exposure
to
granular
carbaryl,
the
number
of
LD50
values
per
square
foot
was
used
to
calculate
RQs
for
mammals
in
the
three
weight
classes.
Avian
Risk
Nongranular
Formulations
Carbaryl
is
slightly
to
practically
nontoxic
to
avian
species
on
an
acute,
and
practically
nontoxic
on
a
subacute
basis.
However,
it
has
been
shown
to
have
chronic
reproduction
effects
(number
of
eggs
produced)
to
the
mallard
at
1000
ppm
and
higher
exposure
levels
(NOAEC
=
300
ppm).
A
detailed
analyses
of
avian
risk
quotients
(RQs)
in
relation
to
their
corresponding
levels
of
concern
(LOCs)
is
presented
in
Appendix
B.
The
avian
acute
risk
level
of
concern
(LOC)
is
not
exceeded
for
any
nongranular
carbaryl
use
at
maximum
nor
less
than
maximum
label
application
rates.
The
avian
chronic
risk
LOC
is
exceeded
for
almost
all
(73
of
74)
nongranular
uses
considered
at
maximum
label
rates,
for
34
of
42
uses
at
maximum
reported
rates,
and
for
39
of
70
uses
at
"average"
rates.
(Appendix
B,
Tables
4,
5a,
and
5b).
Thus,
although
no
nongranular
uses
are
likely
to
present
an
acute
risk
to
birds,
most
uses
are
expected
to
pose
a
significant
chronic
risk
(i.
e.
reproduction
effects)
to
birds.
48
Granular
Formulations
The
avian
acute,
restricted
use,
and
endangered
species
LOCs
are
exceeded
(RQs:
0.52
4.76
for
birds
in
the
20
g
weight
class,
for
all
(about
40)
granular
carbaryl
uses.
The
acute
risk
LOC
is
also
exceeded
(RQ:
0.53)
for
birds
in
the
180
g
weight
class
for
the
trees/
ornamentals,
turfgrass,
and
tick
control
uses.
No
acute
LOCs
are
exceeded
for
birds
in
the
1000
g
weight
class
for
any
of
the
granular
carbaryl
uses
(Appendix
B,
Table
6).
The
avian
endangered
species
LOC
is
exceeded
for
20
g
and
180
g
birds
for
most
uses.
Mammalian
Risk
Risk
to
Herbivores/
Insectivores:
Nongranular
Formulations
Risk
Quotients
for
Herbivores/
Insectivores
Based
on
Less
than
Maximum
Label
Use
Rates
In
addition
to
maximum
label
use
rates,
mammalian
acute
and
chronic
RQs
were
also
calculated
for
nongranular
carbaryl
using
QUA
average
use
rates
data
available
for
70
uses
(Appendix
B,
Table
10a)
and
maximum
reported
(Doane
data)
use
rates
data
available
for
42
uses
(Appendix
B,
Table
10b).
As
summarized
in
Table
10a,
when
RQs
are
based
on
QUA
average
rates,
the
acute
risk
LOC
is
exceeded
for
63
of
the
70
uses
(RQs
=
0.53
4.02),
whereas
the
restricted
use
LOC
is
exceeded
for
69
uses
(not
exceeded
only
for
cabbage),
and
the
endangered
species
LOC
is
exceeded
for
all
70
uses.
The
chronic
risk
LOC
is
exceeded
for
69
of
the
70
uses
(RQs:
1.5
15.9).
When
RQs
are
calculated
using
maximum
reported
application
rates,
the
acute
risk
LOC
is
exceeded
for
41
of
the
42
uses
(RQs:
0.60
11.36),
while
the
restricted
use,
endangered
species,
and
chronic
(RQs:
1.5
45)
risk
LOCs
are
exceeded
for
all
42
uses
(Table
10b).
Risk
Quotients
for
Herbivores/
Insectivores
Based
on
Maximum
Label
Use
Rates
Carbaryl
is
moderately
toxic
to
small
mammals
on
an
acute
oral
basis
(rat
LD50
=
301
mg/
kg),
and
has
the
potential
for
mammalian
chronic
effects
(LOAEC
=
600
ppm
,
NOAEC
=
80
ppm,
based
on
decreased
fetal
body
weights
and
increased
incomplete
ossification
of
multiple
bones
in
the
laboratory
rat).
A
detailed
analysis
of
mammalian
RQs
in
relation
to
their
corresponding
levels
of
concern
(LOCs)
is
presented
in
Appendix
B.
Food
items:
short
grass
The
mammalian
acute
risk
LOC
is
exceeded
for
all
registered
nongranular
carbaryl
uses,
at
maximum
label
application
rates,
for
small
(15
and
35
g)
short
grass
feeders
with
a
daily
food
consumption
equal
to
95%
and
66%
of
their
body
weight,
with
RQ
values
ranging
from
0.76
to
12.12
and
from
0.53
to
8.42,
respectively
(Appendix
B,
Table
7).
Similarly,
the
acute
risk
LOC
for
1000
g
herbivores
with
a
daily
food
consumption
equal
to
15%
of
their
body
49
weight
is
exceeded
for
all
uses
(RQs:
0.56
1.91),
except
rice,
sunflower,
sugar
beets,
wheat,
millet,
flax,
pasture,
grasses,
noncropland,
alfalfa,
clover,
rangeland,
and
forested
areas.
Food
items:
broadleaf/
forage
plants
and
small
insects
At
maximum
label
application
rates,
the
acute
risk
LOC
is
exceeded
for
all
nongranular
carbaryl
uses,
except
rangeland,
for
15
g
(RQs:
0.80
6.82)
and
35
g
(0.55
4.74)
small
mammals
feeding
on
broadleaf/
forage
plants
and
small
insects.
For
1000
g
mammals
consuming
15
%
of
their
body
weight,
the
acute
risk
LOC
is
reached
or
exceeded
for
only
the
citrus,
olives,
pome
fruits,
stone
fruits,
tree
nuts,
sweet
corn,
asparagus,
small
fruits
and
berries,
and
turfgrass
uses
(RQs:
0.52
1.08),
although
the
restricted
use
and/
or
the
endangered
species
LOCs
are
exceeded
for
most
other
uses.
Food
items:
fruits,
pods,
seeds,
and
large
insects
For
small
mammals
consuming
95%
of
their
body
weight
in
fruits,
pods,
seeds,
and
large
insects,
the
acute
risk
LOC
is
exceeded
for
the
citrus,
olives,
tree
nuts,
sweet
corn,
turfgrass
uses
(RQs:
0.62
0.76).
Most
other
registered
uses
(pome
and
stone
fruits,
field
corn,
asparagus,
cucurbits,
trees
and
ornamentals,
solanaceous
crops,
sweet
potatoes,
peanuts,
tobacco,
leafy
vegetables,
Brassica
crops,
roots
and
tubers,
sorghum,
small
fruits
and
berries),
however,
exceed
the
acute
restricted
use
LOC,
while
rice,
sunflower,
sugar
beets,
wheat,
millet,
flax,
pasture,
grasses,
noncropland,
alfalfa,
and
clover
exceed
the
acute
endangered
species
LOC.
For
mammals
consuming
66%
of
their
body
weight
the
acute
risk
LOC
is
exceeded
only
for
use
on
citrus
in
California
(RQ:
0.53);
the
acute
restricted
use
LOC
is
exceeded
for
the
following
uses:
citrus,
olives,
pome
and
stone
fruits,
tree
nuts,
sweet
corn,
asparagus,
solanaceous
crops,
sweet
potatoes,
peanuts,
tobacco,
small
fruits,
berries,
and
turfgrass
(RQs:
0.22
0.49
);
and
the
acute
endangered
species
LOC
is
reached
or
exceeded
for
field
corn,
cucurbits,
trees
and
ornamentals,
leafy
vegetables,
Brassica
crops,
roots
and
tubers,
sorghum,
legumes,
alfalfa,
and
clover
(RQs:
0.11
0.18).
For
mammals
that
consume
15%
of
their
body
weight,
neither
acute
risk
nor
acute
restricted
use
LOC
is
exceeded
for
any
registered
uses,
although
the
acute
endangered
species
LOC
is
reached
or
exceeded
for
a
few
uses
(citrus,
olives,
tree
nuts,
sweet
corn,
and
turfgrass),
with
RQs
in
the
0.1
0.12
range.
Risk
to
Granivores:
Nongranular
Uses
Neither
the
acute
risk
nor
the
acute
restricted
use
LOC
is
exceeded
for
granivores
for
any
of
the
nongranular
carbaryl
uses.
However,
the
acute
endangered
species
LOC
is
reached
or
exceeded
for
the
citrus,
olives,
pome
and
stone
fruits,
tree
nuts,
sweet
corn,
and
turfgrass
use
sites
(RQs:
0.10
0.16
as
well
as
for
the
citrus,
olives,
tree
nuts,
sweet
corn,
and
turfgrass
use
sites
(RQs:
0.10
0.12
for
granivores
with
daily
food
consumption
equal
to
21%
and
15%
of
their
body
weight,
respectively.
No
acute
LOCs
are
exceeded
for
granivores
which
consume
daily
3%
of
their
body
weight.
Chronic
Risk:
Nongranular
Uses
50
At
maximum
label
application
rates,
the
mammalian
chronic
LOC
(1)
is
exceeded
for
all
registered
uses
of
nongranular
carbaryl
for
all
food
item
groups,
with
chronic
RQ
values
in
the
3.0
48.0
range
(for
short
grasses),
1.4
22.0
range
(for
tall
grasses),
and
1.7
27.0
range
(for
broadleaf/
forage
plants,
small
insects).
The
mammalian
chronic
LOC
is
exceeded
for
the
fruits/
pods/
seeds/
large
insects
food
items
for
the
following
uses:
citrus,
olives,
pome
and
stone
fruits,
tree
nuts,
field
and
sweet
corn,
asparagus,
solanaceous
vegetable
crops,
sweet
potatoes,
peanuts,
tobacco,
small
fruits
and
berries,
and
turfgrass
(chronic
RQs
=
1.0
3.0).
These
data
are
summarized
in
Appendix
B,
Table
9.
Risk:
Granular
Uses
At
maximum
application
rates,
RQs
exceed
the
acute
risk
LOC
for
15
g
mammals
(RQs:
2.26
20.71)
and
35
g
mammals
(RQs:
0.97
8.87)
for
all
40
registered
granular
uses.
For
the
1000
g
mammal
category,
the
acute
restricted
use
LOC
is
exceeded
for
the
trees/
ornamentals,
turfgrass,
and
tick
control
uses.
Reproduction
Effects
Field
and
laboratory
studies
conducted
in
the
1970s,
some
of
them
in
former
Soviet
Union
countries,
suggest
that
exposure
to
carbaryl
may
affect
reproduction
in
mammals.
For
instance,
in
a
field
study
undertaken
by
Smirnov
et
al.
(1971),
the
vegetation
around
colonies
of
ground
squirrels
(Rhombomys
opimus
Licht.)
was
treated
with
carbaryl
at
0.5
g/
m
2
(4.45
lb/
acre)
within
a
radius
of
15
m.
Carbaryl
residues
in
plants
around
dens
and
in
food
stored
in
dens
were,
respectively,
above
0.03
mg/
kg
and
0.02
mg/
kg
four
months
after
treatment.
The
percentage
of
lactating
females
was
5.
9%
in
the
treated
area
and
31.
6%
for
control
females.
In
the
treated
areas,
41.
2%
of
all
females
were
inactive
in
mid
May,
while
28.9%
of
females
were
inactive
in
the
untreated
colonies.
Rates
of
fetal
resorption
were
41.9%
in
the
test
group
and
1.08%
in
the
control
group.
The
average
number
of
embryos
per
female
was
6
in
the
treated
group
and
7.
4
in
the
control
group.
Exposure
to
a
single
field
application
of
0.1
5
kg/
ha
of
carbaryl
in
areas
spanning
several
climatic
zones
of
the
former
USSR
resulted
in
adverse
effects
in
lemmings,
voles,
moles,
pikas,
and
gerbils,
including
disturbances
in
spermatogenesis,
pathological
pregnancy,
increased
embryonal
resorption,
increased
percentages
of
infertile
females,
males
with
underdeveloped
testicles,
reduction
of
the
number
of
embryos
per
pregnancy
and
changes
in
population
structures
(Krylova
et
al.,
1975).
In
the
year
of
treatment,
carbaryl
residues
were
present
in
livers
(1.4
3
mg/
kg),
testes
(3.6
12.5
mg/
kg),
uteri
(2
5
mg/
kg)
and
embryos
(1.9
3.3
mg/
kg),
as
well
as
in
these
species'
natural
food
(1.5
mg/
kg).
Carbaryl
was
found
in
grass
(0.08
mg/
kg)
for
as
long
as
2
years
after
treatment.
During
the
year
of
treatment,
there
was
a
significant
reduction
of
only
the
mole
population
in
the
treated
areas,
but
during
the
following
1
3
years
there
were
significant
reductions
in
the
populations
of
all
five
species.
Pomeroy
and
Barrett
(1975)
report
that
a
population
of
cotton
rats
(Sigmodon
hispidus)
inhabiting
a
plot
that
had
been
treated
with
a
single
application
of
carbaryl
had
a
lower
peak
population
density
than
in
a
nontreated,
control
plot.
During
winter,
reproduction
ceased,
and
the
51
cotton
rats
lost
weight
in
the
treated
area,
whereas
rats
in
the
nontreated
area
maintained
or
gained
weight.
Also,
a
population
of
house
mice
that
was
present
in
the
study
area
continued
to
reproduce
in
the
treated
plot,
although
at
a
reduced
rate,
further
indicating
the
potential
to
disrupt
mammal
reproduction.
Pregnant
dogs
treated
with
carbaryl
via
diet
at
0,
2.0,
5.0,
and
12.5
mg/
kg/
day
from
day
1
of
gestation
until
their
pups
were
weaned
at
6
weeks
of
age
resulted
in
a
slight
increase
in
stillbirths
and
a
slight
reduction
in
survival
until
weaning,
although
no
teratogenic
effects
were
observed
(Anonymous,
1969).
Dietary
exposure
to
carbaryl
at
levels
up
to
2000
ppm
did
not
affect
reproduction
in
house
mice
(DeNorscia
and
Lodge,
1973).
According
to
Gladenko
et
al.
(1970),
a
considerable
reduction
of
fecundity
and
litter
size
was
observed
in
rats
fed
daily
10
mg
of
carbaryl
for
138
days,
and
pesticide
residues
were
detected
in
embryos.
Narotsky
and
Kavlock
(1995)
report
that
carbaryl
fed
to
pregnant
rats
showed
a
slight
potential
for
developmental
toxicity.
Chapin
et
al.
(1997),
however,
found
no
changes
in
sex
organ
structure
or
reproductive
function
of
male
or
female
rats
treated
as
juveniles
with
carbaryl
at
0,
6,
12,
or
25
mg/
kg/
day.
Feeding
2
or
20
mg/
kg
of
carbaryl
to
pregnant
rhesus
monkeys
(Macacca
mulatta)
throughout
gestation
did
not
produce
teratologic
effect,
although
treatment
apparently
caused
a
higher
rate
of
abortion
as
compared
with
controls
(Dougherty
et
al.,
1971).
In
a
related
study,
pregnant
rhesus
monkeys
received
either
0.2,
2
or
20
mg/
kg
of
carbaryl
per
day
by
stomach
tube
from
day
20
to
day
28
of
gestation.
Females
were
observed
during
pregnancy,
and
offspring
were
followed
for
one
year
following
birth.
None
of
the
pregnant
monkeys
showed
signs
of
toxicity.
There
were
no
statistical
differences
between
controls
and
monkeys
receiving
up
to
20
milligrams
of
carbaryl
in
terms
of
birth
weights,
gestation
lengths,
or
infant
growth
rates.
There
were
no
significant
differences
observed
in
plasma
or
red
blood
cell
cholinesterase
concentrations.
Examination
of
aborted
animals,
still
births
and
live
infants
revealed
no
teratogenic
signs
(Dougherty,
1975).
Insects
Although
EFED
does
not
assess
risk
to
nontarget
insects
at
present,
data
from
acceptable
guideline
and
nonguideline
studies
are
used
to
recommend
appropriate
label
precautions.
Technical
carbaryl
is
highly
toxic
to
honey
bees
(LC50
=
1.3
2.0
ug/
bee)
and
carbaryl
containing
products
should
be
applied
only
under
the
conditions
specified
by
the
pollinator
protection
label
language.
An
important
factor
in
determining
the
degree
of
carbaryl
hazard
to
honey
bees
is
the
formulation
type.
Certain
formulations,
such
as
baits
and
granulars,
present
little
or
no
hazard
to
bees
due
to
the
low
potential
for
exposure,
whereas
other
formulations,
such
as
dusts,
wettable
powders,
and
flowables
may
pose
a
hazard
from
direct
contact
as
well
as
from
extended
residual
toxicity.
The
honey
bee
is
a
beneficial
arthropod
that
plays
a
major
role
in
pollinating
wild
plants
and
crop
plants
including
fruits,
vegetables,
and
herbs.
Toxic
compounds
present
in
air,
soil
and
water
not
only
can
hit
the
foraging
bee,
but
can
also
be
concentrated
and
stored
in
the
beehive
before
being
consumed
by
emerging
broods
or
overwintering
bees.
Sublethal
doses
of
carbaryl
can
disturb
the
52
reproductive
behavior,
dispersal
behavior,
feeding
behavior,
and
locomotion
of
bees,
all
of
which
can
lead
to
disorders
in
population
dynamics.
Carbaryl
has
often
been
implicated
in
bee
kills,
which
is
not
surprising
considering
that
this
chemical
is
an
effective
wide
spectrum
insecticide
with
multiple
agricultural
and
urban
uses.
For
instance,
carbaryl
was
one
of
three
insecticides
responsible
for
most
of
the
114
bee
kill
incidents
reported
for
Washington
State
during
the
1992
1996
period
(Johansen,
1997).
The
other
two
chemicals
were
chlorpyrifos
and
micro
encapsulated
methyl
parathion.
Similarly,
in
1997
the
American
Beekeeping
Federation
ranked
carbaryl
as
third
in
importance
among
pesticides
reported
as
responsible
for
most
bee
mortality
incidents
in
the
U.
S.
(Brandi,
1997).
Bee
kill
incidents
involving
carbaryl
in
several
states,
including
North
Carolina,
South
Dakota,
and
Washington
have
been
reported
to
the
Agency.
Carbaryl,
being
moderately
to
highly
toxic
to
a
wide
range
of
predaceous
and
parasitic
arthropods,
many
of
which
are
natural
enemies
of
insects
and
mites
injurious
to
agriculture,
is
expected
to
pose
an
acute
risk
to
such
organisms.
Terrestrial
Plants
Although
primarily
an
insecticide/
acaricide,
carbaryl
can
have
adverse
effects
in
some
terrestrial
plants.
Carbaryl
is
used
as
a
fruit
thinning
agent
on
apples
and
pears,
but
precautionary
label
language
cautions
that
it
may
cause
fruit
deformity
under
certain
environmental
conditions,
and
applications
to
wet
foliage
or
during
periods
of
high
humidity
may
cause
injury
to
tender
foliage.
Carbaryl
may
also
cause
injury
to
Boston
ivy,
Virginia
creeper,
maidenhair
fern,
and
Virginia
and
sand
pines.
Plant
incidents
classified
as
probable
include
damage
to
potatoes,
tomatoes,
cabbage,
broccoli
in
Pennsylvania
and
Florida
(I009305
001,
I010017
016).
The
registrant
should
submit
a
Tier
I
Seed
Germination
and
Seedling
Emergence,
as
well
as
Vegetative
Vigor
Studies.
If
25%
or
greater
detrimental
effects
are
found
in
one
or
more
plant
species
in
the
Tier
I
study,
Tier
II
Seed
Germination/
Seedling
Emergence
and
Vegetative
Vigor
studies
should
be
also
submitted.
Guideline
122
1
is
not
fulfilled.
Endangered
Terrestrial
Species
The
endangered
species
LOC
for
birds
is
met
or
exceeded
for
72
of
74
nongranular
carbaryl
uses
at
maximum
label
use
rates,
for
18
of
70
carbaryl
uses
at
QUA
average
use
rates,
and
for
25
of
42
maximum
reported
use
rates.
The
endangered
species
LOC
is
exceeded
for
20
g
birds
for
all
granular
uses.
For
180
g
birds
it
is
exceeded
for
all
granular
uses,
except
cucumber,
melons,
pumpkin,
squash,
beans,
peas,
lentils,
cowpeas,
southern
peas,
wheat,
millet,
and
sugar
beets.
For
1000
g
birds,
the
endangered
species
LOC
is
reached
for
the
trees
and
ornamentals,
turfgrass,
and
tick
control
granular
uses.
The
endangered
species
LOC
for
all
three
mammal
weight
categories
and
the
grass/
broadleaf
plants/
small
insects
food
items
is
exceeded
for
all
nongranular
uses
examined,
at
maximum
label
rates.
At
"average"
and
maximum
reported
use
rates,
the
endangered
species
LOC
53
for
15
g
mammals
feeding
on
short
grass
is
exceeded
for
all
nongranular
uses.
At
maximum
label
rates,
the
endangered
species
LOC
is
exceeded
for
small
(15
and
35
g)
mammals
for
all
granular
uses,
whereas
for
1000
g
mammals,
it
is
exceeded
only
for
the
trees/
ornamentals,
turfgrass,
and
tick
control
granular
uses.
The
endangered
species
LOC
for
freshwater
fish
is
exceeded
for
three
(sweet
corn,
field
corn,
and
citrus)
of
five
use
scenarios
modeled
and
for
the
citrus
scenario
at
less
than
maximum
label
rates.
For
marine/
estuarine
fish,
the
endangered
species
LOC
is
met
for
the
citrus
scenario
only
at
maximum
label
rates.
The
endangered
species
LOC
is
exceeded
for
freshwater
and
marine/
estuarine
aquatic
invertebrates
for
all
five
use
scenarios
at
maximum
and
less
than
maximum
label
use
rates.
Although
no
RQs
are
calculated
for
insects,
considering
its
toxicity
to
arthropods
and
broadspectrum
uses,
carbaryl
is
expected
to
pose
a
risk
to
endangered
species
of
insects
and
other
terrestrial
arthropods.
The
Agency
has
developed
a
program
(the
"Endangered
Species
Protection
Program")
to
identify
pesticides
whose
use
may
cause
adverse
impacts
on
endangered
and
threatened
species,
and
to
implement
mitigation
measures
that
will
eliminate
the
adverse
impacts.
At
present,
the
program
is
being
implemented
on
an
interim
basis
as
described
in
a
Federal
Register
notice
(54
FR
27984
28008,
July
3,
1989),
and
is
providing
information
to
pesticide
users
to
help
them
protect
these
species
on
a
voluntary
basis.
As
currently
planned,
the
final
program
will
call
for
label
modifications
referring
to
required
limitations
on
pesticide
uses,
typically
as
depicted
in
countyspecific
bulletins
or
by
other
site
specific
mechanisms
as
specified
by
state
partners.
A
final
program,
which
may
be
altered
from
the
interim
program,
will
be
described
in
a
future
Federal
Register
notice.
The
Agency
is
not
imposing
label
modifications
at
this
time
through
the
RED.
Rather,
any
requirements
for
product
use
modifications
will
occur
in
the
future
under
the
Endangered
Species
Protection
Program.
8.0
Summary
of
Ecological
Incident
Data
Based
on
information
available
in
the
USEPA
Ecological
Incident
Information
System
(EIIS),
carbaryl
does
not
rank
high
in
the
list
of
pesticides
responsible
for
bird
or
mammal
mortality.
Three
bird
kill
incidents,
involving
blackbirds,
ducks,
starlings,
and
grackles
in
Virginia,
New
Jersey,
and
South
Carolina
have
been
reported
and
classified
as
probable.
Likewise,
there
are
only
two
incidents
involving
small
mammals
(grey
and
ground
squirrels,
mole,
rabbit)
in
South
Carolina
and
Virginia.
On
the
other
hand,
numerous
bee
kill
incidents
have
been
recorded
for
carbaryl
in
several
states,
including
North
Carolina,
South
Dakota,
and
Washington.
In
addition,
several
incidents
on
vegetable
crops,
including
damage
to
potatoes,
tomatoes,
cabbage,
broccoli
classified
as
probable,
have
been
recorded
in
New
York,
Pennsylvania,
and
Florida
(I009305
001,
I010017
016).
The
number
of
documented
incidents
in
the
EIIS
is
believed
to
be
a
small
fraction
of
the
total
mortality
caused
by
pesticides.
Mortality
incidents
must
be
seen,
reported,
investigated
and
the
54
information
submitted
to
EPA
in
order
to
be
recorded
in
the
data
base
(the
states
submit
this
information
on
a
voluntary
basis).
Often
incidents
may
not
be
noted
because
the
carcasses
either
decayed
in
the
field,
were
removed
by
scavengers,
or
were
located
in
out
of
the
way
or
hard
to
see
locations.
For
example,
poisoned
birds
may
fly
off
site
before
dying,
some
species
of
fish
may
sink
and
the
bodies
of
young
fish
can
quickly
decompose
in
the
environment
prior
to
any
notice
of
a
problem.
An
incident
may
also
go
unreported
because
the
finder
may
not
be
aware
of
the
significance
of
the
issue
or
may
not
know
the
appropriate
authorities
for
an
investigation.
Furthermore,
limited
resources
may
hamper
investigations
and
preclude
any
confirmatory
analysis
of
tissue
and
residues.
55
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62
Appendix
A:
Refined
Water
Memo
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
PC
Code:
056801
DP
Bar
Code:
D267276
DATE:
July
23,
2001
MEMORANDUM
SUBJECT:
Refined
Estimated
Environmental
Concentrations
for
Carbaryl
FROM:
E.
Laurence
Libelo,
Ph.
D.,
Environmental
Engineer
Environmental
Risk
Branch
IV
Environmental
Fate
and
Effects
Division
(7507C)
THROUGH:
Elizabeth
Behl,
Chief
Environmental
Risk
Branch
IV,
EFED
(7507C)
TO:
Anthony
E.
Britten,
Chemical
Review
Manager
Betty
Shackleford,
Branch
Chief
Reregistration
Branch
III
Special
Review
and
Reregistration
Division
(7508C)
Virginia
Dobozy,
Ph.
D.,
HED/
RRBI
This
memo
presents
refined
surface
water
and
groundwater
Estimated
Environmental
Concentrations
(EECs)
for
use
in
calculating
human
exposure
to
carbaryl.
These
values
were
determined
using
available
monitoring
data,
modeling
with
PRZM/
EXAMS
for
surface
water,
and
SCI
GROW
for
groundwater.
EEC
values
are
shown
in
Table
1.
Because
of
uncertainties
in
available
monitoring
data
EFED
recommends
using
modeling
results
in
assessing
Carbaryl
risks.
Background:
Chemical
characteristics
and
available
monitoring
data
indicate
that
carbaryl
has
the
potential
to
enter
surface
water
via
leaching
and
runoff
under
certain
conditions
and
has
limited
potential
to
leach
to
ground
water.
Carbaryl
tends
not
to
partition
to
soil,
aquifer
solids,
or
63
sediment.
Once
the
compound
has
entered
surface
water,
it
may
be
degraded
by
chemical
and
biological
processes.
Abiotic
degradation
by
photolysis
(t1/
2
=
21
days)
and
hydrolysis
in
alkaline
(t1/
2
=
3.2
hours
at
pH
9)
and
neutral
(t1/
2
=
12
days
at
pH
7)
waters
result
in
fairly
rapid
degradation
in
most
aqueous
environments.
Microbially
mediated
processes
also
contribute
to
fairly
rapid
degradation
of
the
parent
to
1
naphthol
and
CO2.
Aerobic
aquatic,
soil
aerobic
and
anaerobic
metabolism
studies
(t1/
2
=
5,
4,
and
72
days
respectively)
suggest
that
the
compound
is
broken
down
by
a
variety
of
metabolic
processes.
Under
certain
conditions
carbaryl
can
be
expected
to
persist
in
the
environment.
Under
low
pH
conditions
the
compound
is
stable
to
hydrolysis.
In
anaerobic
environments
metabolism
is
fairly
slow
(t½
=
72
days).
This
suggests
that
carbaryl
may
leach
to
ground
water
and
persist
in
some
aquifers.
Monitoring
studies
show
that
carbaryl
is
a
commonly
detected
contaminant
in
surface
water.
Carbaryl,
at
typically
low
concentrations,
is
found
in
greater
than
20
%
of
surface
samples
with
concentrations
up
to
7
ppb.
Carbaryl
is
generally
not
widely
detected
in
groundwater
monitoring
studies
though
some
studies
have
found
concentrations
of
up
to
several
hundred
ppb.
Concentrations
as
high
as
610
µg/
L
have
been
detected
in
one
case
but
typical
groundwater
concentrations
are
much
lower.
NAWQA
studies
have
found
that
about
1
%
of
groundwater
samples
have
measurable
levels
(>
0.003
:
g/
L)
of
carbaryl,
with
a
maximum
concentration
of
0.02
µg/
L.
Targeted
studies
designed
to
measure
carbaryl
in
groundwater
are
not
available.
Based
on
chemical
properties,
existing
monitoring
data
and
computer
simulation
estimates
of
carbaryl
contamination
that
can
be
expected
in
surface
water
and
groundwater
as
a
result
of
normal
agricultural
practices
have
been
determined.
Carbaryl
is
commonly
found
in
surface
water,
and
can
be
expected
to
contaminate
drinking
water
derived
from
surface
water
bodies.
Targeted
and
non
targeted
studies
regularly
detect
carbaryl
in
low
concentrations,
typically
below
1
µg/
L.
Carbaryl
use
in
urban
and
suburban
areas
results
in
higher
frequency
of
surface
water
contamination.
Monitoring
data
suggest
that
carbaryl
concentrations
resulting
from
non
agricultural
uses
are
higher
then
from
agricultural
uses.
However,
at
this
time
EFED
does
not
have
methods
for
evaluating
EECs
from
non
agricultural
uses.
Carbaryl
is
not
widely
detected
in
groundwater
studies.
For
drinking
water
derived
from
groundwater,
the
acute
and
chronic
EEC
value
of
0.8
µg/
L
is
based
on
modeling
using
SCIGROW
It
must
be
noted
that
carbaryl
has
an
aerobic
metabolism
half
life
(4
days)
which
is
significantly
outside
the
range
of
values
for
which
SCI
GROW
may
be
valid
(17
1000
days).
Because
of
this
there
is
significant
uncertainty
in
the
SCI
GROW
value.
EFED
currently
does
not
have
more
advanced
groundwater
models,
and
targeted
studies
specifically
designed
to
evaluate
the
potential
for
carbaryl
to
move
to
groundwater
are
not
available.
Because
of
its
chemical
structure
carbaryl
is
somewhat
difficult
to
quantify
by
gas
chromatography.
Older
studies
using
GC
or
GC/
MS
generally
have
poor
recovery
and
6
Maximum
is
the
highest
application
rate
allowed
according
to
the
label
for
the
specific
crop
"Average"
is
the
average
rate
as
determined
by
OPP/
BEAD
and
reported
in
the
a
memo
titled
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD
Maximum
used
is
the
highest
rate
of
application
that
is
actually
reported
to
be
used
based
on
OPP/
BEAD
analysis
of
Doanes
survey
data
64
quantitation
limits.
Because
of
this
difficulty
in
analysis
the
actual
concentration
of
carbaryl
in
groundwater
and
surface
waters
may
be
higher
than
reported.
More
recent
studies
using
HPLC/
MS
should
provide
better
data
on
the
true
extent
and
magnitude
of
water
contamination
from
the
use
of
carbaryl.
Surface
Water
Modeling
Surface
water
EECs
derived
from
computer
modeling
are
higher
than
generally
seen
in
monitoring
studies.
Carbaryl
is
often
detected
in
surface
water,
and
it
is
very
unlikely
that
monitoring
data
represents
actual
maximum
concentrations
or
that
all
occurrences
have
been
sampled.
Because
Carbaryl
is
fairly
reactive
in
the
environment
it
is
difficult
to
design
a
sampling
program
that
can
identify
the
peak
concentrations.
Therefore
EFED
recommends
using
modeling
data
in
human
health
risk
assessment.
Modeling
to
support
the
assessment
of
drinking
water
in
the
human
health
risk
assessment
was
done
for
five
crop
scenario:
Florida
citrus,
Ohio
sweet
corn
and
field
corn,
Oregon
apples
and
Minnesota
sugar
beets.
Three
different
application
rate
scenarios
were
used
in
modeling:
the
maximum
allowed
on
the
label
for
the
specific
crop,
an
"average"
rate,
and
the
maximum
rate
reported
to
actually
be
used
6
.
EECs
were
calculated
using
The
Pesticide
Root
Zone
Model
version
3.12
(PRZM)
(Carsel
et
al.,
1997)
and
EXAMS
2.97.5
(Exposure
Analysis
Modeling
System)
(Burns,
1997).
PRZM
is
used
to
simulate
pesticide
transport
as
a
result
of
runoff
and
erosion
from
an
agricultural
field
and
EXAMS
estimates
environmental
fate
and
transport
of
pesticides
in
surface
water.
Weather
and
agricultural
practices
are
simulated
over
36
years
so
that
the
10
year
exceedance
probability
at
the
site
can
be
estimated.
A
partial
list
of
input
parameters
for
the
PRZM/
EXAMS
modeling
are
given
in
Table
2.
The
values
generated
by
the
models
were
multiplied
by
a
default
percent
crop
area
factor
(PCA)
which
accounts
for
the
fact
that
is
unlikely
for
any
basin
to
be
completely
planted
to
agricultural
crops.
For
human
health
assessment,
simulations
were
done
using
the
Index
Reservoir
scenario
in
Exams.
The
Index
Reservoir
and
PCA
are
described
in
Jones
et
al.,
2000.
The
EEC's
for
the
five
scenarios
simulated
are
shown
in
Table
1.
Input
files
for
PRZM/
EXAMS
modeling
are
attached.
Corn:
Runoff
from
use
on
sweet
and
field
corn
was
modeled
using
a
Ohio
corn
scenario
located
in
the
Scioto
River
valley
of
Central
Ohio.
The
soil
is
a
Cardington
silt
loam,
a
fine,
illitic,
mesic
Aquic
Hapludalfs
in
MLRA
M
111.
The
Cardington
silt
loam
is
a
very
deep,
moderately
well
drained
soil
formed
in
loamy
till
of
medium
lime
content.
Soils
are
located
on
0
15
percent
65
convex
SE
facing
slopes
on
summits,
shoulders,
and
back
slopes
on
Wisconsin
Age
ground
and
end
moraines.
Permeability
is
slow
and
runoff
is
negligible
to
very
high.
An
intermittent
perched
water
table
is
present
between
1
2
feet
from
November
and
April
in
most
years.
The
MAP
is
36
inches
and
the
MAT
is
51
o
F.
Most
areas
are
cultivated.
Major
crops
are
corn,
soybeans,
small
grains,
and
hay.
Some
areas
are
in
pasture.
The
soil
is
characterized
as
Group
C
hydrologic
soil.
The
soil
distribution
includes
Central
and
North
Central
Ohio.
The
series
is
of
large
extent,
approximately
250,000
acres.
The
series
was
established
in
Licking
County
Ohio
in
1930.
A
PCA
of
0.46
was
used
to
correct
calculated
values
for
percent
area
cropped.
Apples:
Runoff
from
application
on
apples
was
modeled
using
a
standard
input
scenario
for
an
orchard
in
Washington
County,
Oregon.
The
soil
at
the
site
is
a
Cornelius
silt
loam
soil,
a
finesilty
mixed,
mesic
Ultic
Haploxeralf
on
a
15%
slope
in
MLRA
2.
Seventy
six
acres
of
pears
and
238
acres
of
apples
were
grown
in
Washington
County
in
1987
(US
Department
of
Commerce,
1989b).
The
weather
data
is
from
weather
station
W24232
in
Salem,
Oregon.
The
weather
data
file
is
also
part
of
the
PIRANHA
shell,
and
is
used
to
represent
the
weather
for
MLRA
2.
The
site
was
selected
to
represent
orchards
in
the
western
United
States
that
are
reasonable
likely
to
result
in
high
exposures
to
aquatic
organisms.
The
pond
used
the
standard
Richard
Lee
pond
that
is
distributed
with
EXAMS
modified
for
the
Index
Reservoir.
Additional
adjustments
were
made
to
the
standard
pond
by
changing
the
water
temperature
to
that
which
was
more
appropriate
for
the
region
being
simulated.
The
temperature
in
the
pond
each
month
was
set
to
the
average
monthly
air
temperature
over
all
36
years
calculated
from
the
meteorological
file
that
was
used
in
the
simulation.
The
default
PCA
of
0.87
was
used.
Sugar
beets:
Runoff
from
application
on
sugar
beets
was
modeled
using
a
standard
scenario
modified
for
the
Index
Reservoir
in
Polk
Co.
MN.
MN
has
the
highest
sugar
beet
acreage
and
Polk
Co.
is
the
highest
in
the
state.
The
soil
at
the
site
is
Bearden
silty
clay
loam,
a
benchmark,
hydrologic
group
C
soil
with
about
800K
mapped
acres
in
MLRA
56.
The
chemical
was
applied
is
two
aerial
applications
of
1.5
lb
a.
i.
per
acre
14
days
apart.
Application
timing
information
provided
by
the
University
of
Minnesota
Agricultural
Extension
Service,
Polk
County,
MN,
EFED
does
not
have
a
PCA
for
sugar
beets
so
the
default
value
of
0.87
was
used.
Citrus
Use
on
citrus
was
modeled
using
the
EFED
standard
citrus
scenario
in
Oceola
County,
Florida.
The
soil
is
a
Adamsville
sand,
a
hyperthermic,
uncoated
Aquic
Quartzipsamment
in
MLRA
156A.
The
Adamsville
sand
is
a
somewhat
poorly
drained,
rapidly
permeable
soil
that
formed
in
thick
sandy
marine
sediments
occurring
in
Central
and
Southern
Florida
on
slopes
of
0
5
percent.
The
soil
is
typical
of
soils
used
either
for
rangeland
or
citrus
production.
66
Adamsville
sand
ranges
from
a
Hydrologic
Group
A
soil
to
a
Hydrologic
Group
C
soil,
depending
on
the
water
table.
For
the
purpose
of
this
modeling,
EFED
assumed
the
curve
numbers
from
the
PIC
of
the
Adamsville
sand
as
a
Group
C
soil.
The
default
PCA
of
0.87
was
used.
EECs
varied
greatly
depending
on
the
geographic
location,
crop
and
application
rate.
Calculated
EECs
range
up
to
about
500
:
g/
L.
The
maximum
calculated
EEC
resulted
from
use
on
citrus
in
Florida.
Modeling
"average"
and
maximum
reported
use
rates
gave
EEC
values
generally
40
60%
lower
than
calculated
with
maximum
rate.
EECs
calculated
by
modeling
are
slightly
higher
than
concentrations
observed
in
monitoring
data.
Because
most
available
monitoring
data
is
not
from
targeted
studies
and
is
limited
spatially
and
temporally
it
is
not
reasonable
to
expect
that
it
represents
the
maximum
environmental
concentrations
that
exist.
Therefore
modeling
results
probably
are
a
better
estimate
of
actual
concentrations
that
may
occur
in
the
environment.
67
Table
1.
Carbaryl
Drinking
Water
EECs
Crop
Number
of
Applications
per
Year
Pounds
A.
I.
per
application
Surface
Water
Acute
(ppb)
(1
in
10
year
peak
single
day
concentration)
Surface
Water
Chronic
(ppb)
(1
in
10
year
annual
average
concentration)
Sweet
Corn
(OH)
(PCA
=
0.46)
Maximum
1
8
2
37
3.2
Average
2
2
3.
4
45
2.2
Maximum
3
Reported
3
1
15
0.9
Field
Corn
(OH)
(PCA
=
0.46)
Maximum
1
4
2
30
2.1
Average
2
2
1
13
0.6
Maximum
3
Reported
2
1.
520
1
Apples
(OR)
(PCA
=
0.87)
Maximum
1
5
2
144
9
Average
2
2
1.
2
12
0.7
Maximum
3
Reported
2
1.
625
1
Sugar
Beets
(MN)
(PCA
=
0.87)
Maximum
1
2
1.
519
2
Average
2
1
1.
5
12
1.1
Maximum
3
Reported
1
1.
2
9
0.
9
Citrus
(FL)
(PCA
=
0.87)
Maximum
1
4
5
494
28
Average
2
2
3.
4
246
11
Maximum
3
Reported
3
4.
26
411
16
Surface
Water
Monitoring
5.5
(Maximum
Observed
Concentration)
Groundwater
SCIGROW
Maximum
1
5
40.
8
0.
8
Groundwater
(NAWQA
Monitoring
Data)
0.02
0.02
1
Maximum
application
rate
on
label
2
Average
application
rate
from
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD
3
Maximum
rate
of
application
reported
in
DoaneS
survey
data
68
Surface
Water
Monitoring
Carbaryl
is
widely
detected
in
surface
waters
in
non
targeted
and
targeted
monitoring
studies.
Observed
concentrations
are
generally
low
(>
0.5
:
g/
L).
Carbaryl
is
not
very
persistent
in
most
surface
water
conditions
suggesting
that
the
wide
spread
occurrence
is
a
result
of
its
extensive
use
in
a
variety
of
applications.
Because
of
limitation
in
the
analytical
methods
used
there
is
some
question
as
to
the
accuracy
of
carbaryl
analysis.
Poor
analytical
methods
probably
have
resulted
in
lower
detection
rates
and
lower
concentrations
than
actually
present.
NAWQA
Carbaryl
is
second
most
widely
detected
incesticide
(after
diazanon)
the
USGS
NAWQA
program
(http://
water.
usgs.
gov/
nawqa/
nawqa_
home.
html).
Carbaryl
was
detected
in
46%
of
36
NAWQA
study
units
between
1991
and
1998.
The
reported
concentrations
are
believed
to
be
reliable
detections
but
have
greater
than
average
uncertainty
in
quantification.
Carbaryl
analytical
results
are
fairly
poor,
with
a
typical
mean
percent
recovery
of
24%
(
F
=
15)
in
laboratory
quality
control
samples,
and
a
method
detection
limit
(MDL)
of
0.003
ug/
L.
This
suggests
that
the
reported
values
do
not
represent
the
maximum
concentrations
that
exist,
and
that
surface
water
contamination
may
be
more
widespread
than
the
data
show.
Out
of
5220
surface
water
samples
analyzed
1082,
or
about
21
percent,
were
reported
as
having
detections
greater
than
the
MDL.
The
maximum
reported
concentration
was
5.5
µg/
L.
For
samples
with
positive
detections
the
mean
concentration
was
0.11
:
g/
L,
with
a
standard
deviation
of
0.43
:
g/
L.
A
significant
portion
of
the
total
carbaryl
applied
was
transported
to
streams.
In
areas
with
high
agricultural
use
the
load
measured
in
surface
waters
was
relatively
consistent
across
the
country
at
about
0.1
percent
of
the
amount
used
in
the
basins
(Larson
et
al.,
1999)
http://
water.
wr.
usgs.
gov/
pnsp/
rep/
wrir984222/
load.
html.
The
estimated
annual
carbaryl
use
on
in
agricultural
applications
is
about
4
million
pounds
suggesting
that
400,000
pounds
are
delivered
each
year
to
the
nations
streams
draining
agricultural
areas.
Streams
draining
urban
areas
showed
more
frequent
detections
and
higher
concentrations
than
streams
draining
agricultural
or
mixed
land
use
areas.
For
example
Kimbrough
and
Litke
(1996)
reported
that,
in
the
South
Platte
River
Basin
Study
Unit,
between
April
and
December
of
1993,
carbaryl
was
detected
in
14
urban
drainage
samples
and
6
agricultural
drainage
samples.
Carbaryl
had
the
highest
concentration
of
the
four
insecticides
analyzed
with
a
maximum
concentration
of
2.5
:
g/
L
in
the
urban
basin
and
1.5
:
g/
L
in
the
agricultural
basin
(http://
webserver.
cr.
usgs.
gov/
nawqa/
splt/
meetings/
KIMB1.
html).
In
the
South
Central
Texas
Study
Unit
carbaryl
was
detected
in
12%
of
streams
draining
agricultural
areas
and
52
%
draining
urban
areas
(Bush
et
al.,
2000)
http://
water.
usgs.
gov/
pubs/
circ/
circ1212/.
69
Registrant
Monitoring
Study
Aventis
Crop
Science
submitted
interim
results
of
an
on
going
surface
water
monitoring
study.
Carbaryl
residues
in
surface
water
were
measured
at
drinking
water
facilities
in
areas
believed
to
have
high
agricultural
and
residential
use
(MRID
45116201).
In
this
study
16
sites
were
in
agricultural
areas
and
4
in
areas
draining
suburban
areas.
Samples
of
raw
water
were
collected
at
municipal
water
treatment
facilities
for
8
12
months.
When
raw
water
showed
positive
detections
for
carbaryl,
finished
water
samples
collected
at
the
same
time
were
analyzed.
Samples
were
collected
weekly
during
periods
suspected
of
being
"high
risk"
and
monthly
the
rest
of
the
year
in
agricultural
areas.
Suburban
sites
were
sampled
weekly.
In
this
study
carbaryl
was
analyzed
by
HPLC/
MS
with
a
limit
of
detection
of
0.002
ppb
and
a
limit
of
quantitation
(LOQ)
of
0.030
ppb.
Most
carbaryl
detections
in
this
study
were
below
the
LOQ.
In
raw
water
samples
from
suburban
sites
detectable
residues
in
raw
water
ranged
from
0.002
to
0.023
ppb.
11
out
of
40
raw
water
samples
from
Sweetwater
Creek,
the
source
of
water
for
the
East
Port
facility
in
Douglas,
GA
had
detectable
levels
ranging
from
0.002
to
0.018
ppb.
One
out
of
46
samples
from
Joe
Pool
Lake,
Ellis
Texas
had
a
detection
at
0.014
ppb.
Jorden
Lake
in
Cary,
NC
had
2
detections
out
of
44
samples
(0.004
and
0.003
ppb).
11
out
of
40
samples
from
the
Cahaba
River
in
Birmingham
AL
had
detections
ranging
from
0.002
to
0.023
ppb.
Finished
water
sampled
from
suburban
areas
were
all
below
the
detection
limit.
In
samples
from
agricultural
sites
9
out
of
15
water
sources
had
some
detectable
level
of
carbaryl.
The
detections
were
generally
at
low
levels,
with
one
of
about
0.16
ppb
and
one
of
0.031.
The
rest
were
below
the
level
of
quantitation
(<
0.03
ppb).
Samples
from
finished
water
were
generally
lower
than
raw
water,
though
it
appears
that
raw
and
finished
water
sampling
did
not
sample
the
same
mass
of
water.
Therefore,
the
data
can
not
be
used
to
evaluate
the
effectiveness
of
water
treatment
on
carbaryl.
Because
the
samples
were
collected
at
the
same
time,
the
water
exiting
the
treatment
plant
was
temporally
different
than
the
water
entering
and
represent
different,
independent,
parcels
of
water.
In
several
cases
finished
water
had
higher
concentrations
than
raw
water,
and
finished
water
had
detectable
carbaryl
when
the
raw
did
not.
The
highest
concentration
measured
was
in
finished
water
(0.16
ppb).
Raw
water
sampled
at
the
same
time
had
much
lower
concentration
(0.010).
This
illustrates
that
carbaryl
contamination
is
transient,
and
that
it
is
unlikely
that
any
but
the
most
intensive
sampling
would
ever
detect
the
actual
peak
concentration.
That,
and
the
limited
number
of
sites
sampled,
limit
the
usefulness
of
this
study.
Non
targeted
monitoring,
such
as
the
NAWQA
program,
has
shown
that
much
higher
concentrations
occur
indicating
that
this
study,
while
useful,
can
not
be
used
to
describe
the
overall
distribution
of
concentrations
that
occur
throughout
the
entire
use
area.
This
study
does
not
provide
sufficient
information
to
allow
estimation
of
actual
peak
and
mean
concentrations
that
actually
occur
in
all
use
areas.
The
highest
concentration
values
measured
in
this
study
are
close
to
the
average
values
seen
in
other,
non
targeted,
studies.
70
Only
limited
information
was
submitted
on
sampling
site
selection
and
how
the
sites
relate
to
the
overall
distribution
of
use
areas.
Home
and
garden
sites
were
selected
downstream
of
urban/
suburban
areas
that
were
believed
to
have
high
use
based
on
county
scale
sales
data.
Agricultural
sites
were
selected
based
on
county
scale
sales
data,
and
are
believed
to
be
in
"major
use
counties."
This
study
is
still
ongoing
and
only
interim
study
results
have
been
submitted.
Additional
information
is
needed
to
evaluate
the
study
results.
Additionally,
an
analysis
of
how
the
selected
sites
relate
to
the
nationwide
distribution
of
use
areas
is
required.
This
should
include
an
explanation
of
why
this
study
did
not
observe
concentrations
as
high
as
those
found
in
other,
non
targeted
studies,
and
how
the
results
of
this
study
can
be
related
to
concentrations
that
occur
throughout
the
country.
Based
on
the
interim
data
submitted
it
appears
that
this
study
measured
concentrations
similar
to
those
observed
in
non
targeted
studies
and
did
not
capture
high
end
or
peak
values.
This
study
appears
to
be
well
designed
though
limited
but
until
additional
information
is
submitted
it
is
not
possible
to
use
the
interim
results
for
more
then
to
reinforce
the
inferences
drawn
from
non
targeted
study
data.
STORET
The
EPA
STORET
database
(
was
queried
on
May
12,
1999
for
reports
of
measurements
of
carbaryl
in
surface
water.
The
database
contained
8048
records
indicating
that
analysis
was
done
for
carbaryl.
Out
of
these
432
reported
concentrations
above
the
detection
limits.
The
maximum
value
reported
was
5.5
µg/
L.
Of
the
reported
detections
18
were
above
1
ppb.
The
data
is
the
STORET
database
is
used
to
give
a
general
indication
of
the
occurrence
pattern
only.
Lack
of
QA/
QC
and
analytical
methodology
limitations
limit
the
usefulness
of
the
STORET
data.
However,
reported
detections
of
carbaryl
suggest
that
the
compound
is
infrequently
detected
in
surface
water
and
at
low
levels.
Groundwater
Available
evidence
from
valid
scientific
studies
show
that
carbaryl
has
a
limited
potential
to
leach
to
ground
water,
and
as
a
result
of
normal
agricultural
use,
detections
of
carbaryl
residues
have
been
reported
in
groundwater
from
several
states.
As
reported
in
the
U.
S.
EPA.
Pesticides
in
Groundwater
Database
(Jacoby
et
al.,
1992)
carbaryl
was
detected
in
0.4%
of
wells
sampled.
Carbaryl
was
detected
in
California
(2
out
of
1433
wells),
Missouri
(11
out
of
325
wells),
New
York
(69
out
of
21027
wells)
Rhode
Island
(13
out
of
830
wells)
and
Virginia
(11
out
of
138
wells).
The
maximum
concentration
detected
was
610
µg/
L
in
NY,
though
typically
the
measured
concentrations
were
significantly
lower.
The
EPA
STORET
database
was
queried
on
May
12,
1999
for
reports
of
measurements
of
carbaryl
in
groundwater.
The
database
contained
9389
records
indicating
that
analysis
was
done
for
carbaryl.
Out
of
these
only
4
reported
concentrations
above
the
detection
limits.
These
analyses
were
all
from
one
well
in
Cleveland,
OK
in
1988.
The
4
reported
concentrations
were
between
0.8
and
1
ppb.
71
Carbaryl
was
detected
at
greater
than
the
detection
limit
(0.003
µg/
L)
in
1.1
%
of
groundwater
samples
from
1034
sites
across
the
U.
S.
by
U.
S.
G.
S.
NAWQA
program.
The
maximum
observed
concentration
was
0.021
µg/
L.
Detections
were
from
mainly
from
three
use
sites:
wheat
(5.8
%
of
well
samples
from
wheat
land
use
),
orchards
and
vineyards
(1.7
%
of
well
samples
from
orchard
and
vineyard
land
use),
and
urban
(1.8%
of
urban
groundwater
samples).
Limitations
in
analytical
methodology
(described
elsewhere)
apply
to
groundwater
sample
analysis
also
suggesting
that
there
actual
maximum
concentrations
and
extent
of
contamination
may
be
significantly
higher.
Data
on
pesticides
in
groundwater
were
reviewed
by
Kolpin
et
al.
(1998)
and
updated
information
is
available
at:
http://
water.
wr.
usgs.
gov/
pnsp/
ja/
est32/.
For
drinking
water
derived
from
groundwater
an
acute
and
chronic
EEC
value
of
0.8
µg/
L
should
be
used
based
on
modeling
using
SCIGROW.
Carbaryl
is
not
frequently
detected
in
groundwater
monitoring
studies.
However,
targeted
studies
specifically
designed
to
evaluate
the
potential
for
carbaryl
to
move
to
groundwater
are
not
available.
SCI
GROW
is
used
to
calculate
a
groundwater
screening
exposure
value
to
be
used
in
determining
the
potential
risk
to
human
health
from
drinking
water
contaminated
by
use
of
pesticides.
In
the
case
of
Carbaryl
the
chemical
properties
of
the
compound
are
outside
the
range
of
values
for
which
SCI
GROW
was
developed.
The
EEC
value
calculated
using
SCI
GROW
should
therefore
be
used
with
caution
since
it
may
significantly
underestimate
possible
groundwater
concentrations.
SCI
GROW
input
parameters
are
shown
in
Table
2
and
a
copy
of
the
output
is
attached..
Water
Treatment
Effects
The
Office
of
Pesticide
Programs
has
completed
a
review
of
the
effects
of
drinking
water
treatment
on
pesticides
in
water
(http://
www.
epa.
gov/
scipoly/
sap/
2000/
september/
sept00
sap__
dw
0907.
pdf).
This
review
indicates
that
standard
drinking
water
treatment,
consisting
of
flocculation/
sedimentation
and
filtration
does
not
substantially
affect
concentrations
of
pesticides
in
drinking
water.
Evidence
suggests
that
carbaryl
does
not
react
with
chlorine
or
hypoclorite
disinfection
products
in
water
treatment
but
is
rapidly
degraded
(T½
=
too
rapid
to
measure)
by
ozone
(Mason
et
al.,
1990).
72
Table
2.
PRZM/
EXAMS
environmental
fate
input
parameters
for
Carbaryl
Parameter
Value
Data
source
Molecular
Weight
201.22
Solubility
32
mg/
L
(@
20°
C)
Suntio,
et
al.,
1988
Vapor
Pressure
(torr)
1.36
10
6
@
25°
C
Ferrira
and
Seiber,
1981
Henry's
Law
Constant
1.28
x
10
8
Suntio,
et
al.
1988
Hydrolysis
Half
life
pH
5
pH
7
pH
9
stable
stable
5
hours
MRID
00163847
44759301
Soil
Photolysis
Half
life
(days)
stable
no
valid
data
submitted
Aquatic
Photolysis
Half
life
(days)
21
days
MRID
41982603
Aerobic
Soil
Metabolism
Half
life
4.0
days
(n=
1
so
use
3x)
MRID
42785101
Aerobic
Aquatic
Metabolism
Half
life
4.9
days
(n
=
1
so
use
3x)
MRID
43143401
Anaerobic
Aquatic
Metabolism
Half
life
72.2
days
MRID
42785102
Soil
Water
Partitioning
Coefficient
Kads
(Koc)
1.74
(207)
sandy
loam
2.0
(249)
clay
loam
3.0
(211)
silt
loam
3.5
(177)
silty
clay
loam
(Koc
=
211
for
SCIGROW)
MRID
43259301
References
Cited:
Bush,
Peter
W.,
Ann
F.
Ardis,
Lynne
Fahlquist,
Patricia
B.
Ging,
C.
Evan
Hornig,
and
Jennifer
Lanning
Rush,
2000.
Water
Quality
in
South
Central
Texas,
1996
98.
Water
Resources
Circular
1212.
U.
S.
Geological
Survey.
Burns,
L.
A.,
1997.
EXAMS
2.97.5
Users
Manual.
National
Exposure
Research
Lab,
Office
of
73
Research
and
Development,
U.
S.
Environmental
Protection
Agency,
Athens,
Georgia.
Carsel,
R.
F.,
Imhoff,
J.
C.,
Hummel,
P.
R.,
Cheplick,
J.
M.
and
Donigan,
A.
S.,
1997.
PRZM
3.1
Users
Manual.
National
Exposure
Research
Lab,
Office
of
Research
and
Development,
U.
S.
Environmental
Protection
Agency,
Athens,
Georgia.
Ferreira,
G.
A.
and
J.
N.
Seiber,
1981.
J.
Agric.
Food
Chem.,
29:
93
99
Jacoby,
H.,
C.
Hoheisel,
J.
Karrie,
S.
Lees,
L.
Davies
Hilliard,
P.
Hannon,
R.
Bingham,
E.
Behl,
D.
Wells,
and
E.
Waldman.
1992.
Pesticides
in
Ground
Water
Database
A
Compilation
of
Monitoring
Studies:
1971
1991,
EPA
734
12
92
001,
September
1992.
Jones,
R.
David,
Jim
Breithaupt,
Jim
Carleton,
Laurence
Libelo,
Jim
Lin,
Robert
Matzner,
Ron
Parker,
William
Feeland,
Nelson
Thurman
and
Ian
Kennedy,
2000.
Draft
Guidance
for
Use
of
the
Index
Reservoir
and
Percent
Crop
Area
Factor
in
Drinking
Water
Assessments.
EPA/
OPP
Draft
dated
March
3,
2000.
Kimbrough,
R.
A.,
and
Litke,
D.
W.,
1996.
Environ.
Sci.
and
Technol.,
30:
908
916.
Kolpin,
Dana
W.,
Jack
E.
Barbash
and
Robert
Gilliom,
1998.
Environ.
Sci.
Technol.
32:
588
566.
Larson,
Steven
J.,
Robert
Gilliom,
and
Paul
Capel,
1999.
Pesticides
in
Streams
of
the
United
States
Initial
Results
from
the
National
Water
Quality
Assessment
Program.
U.
S.
G.
S.
WaterResources
Investigations
Report
98
4222.
Suntio,
L.
R.,
et
al.,
1988.
Rev.
Environ.
Contam.
Toxicol.,
103:
1
59.
74
APPENDIX
A1:
PRZM
Input
Files
Maximum
Application
Rate
Ohio
Sweet
Corn,
Index
Reservoir
***
PRZM3
Input
File
for
INDEX
RESERVOIR,
IROHCORN1.
inp
converted
3/
30/
2000
***
***
Modeler:
S.
Abel
***
***
Modified
for
CARBARYL
by
Laurence
Libelo,
6/
20/
00
***
Manning's
N
values
for
cornstalk
residue,
fallow
surface,
1
ton/
acre
***
***
Cardington
silt
loam
is
not
one
of
the
benchmark
soils
***
***
Benchmark
soils
include:
blount;
crosby;
pewamo;
miami;
brookston;
glynwood
***
***
miamian;
morley;
bennington;
and
fincastle
***
***
IR
Spray
Drift:
Aerial:
0.16;
Orchard
air
blast:
0.063;
Ground
spray:
0.064
***
***
Application
efficiency:
0.95
aerial;
0.99
spray
blast
and
ground
spray
***
***
PCA
for
corn
=
0.46
***
CARBARYL
Location:
OH
Crop:
corn
MLRA
111
***
RECORD
3
***
0.72
0.30
0
15.00
1
3
***
RECORED
4
***
4
***
RECORD
7
***
0.37
0.43
0.50
172.8
5.80
3
6.00
600.0
***
RECORD
8
***
1
***
RECORD
9
***
1
0.25
90.00
100.00
3
91
85
88
0.00
100.00
***
RECORD
9A
***
1
3
***
RECORD
9B,
C,
D
0101
1605
1110
0.50
0.25
0.30
0.02
0.02
0.02
***
RECORD
10
***
36
***
RECORD
11
*
160548
260948
111048
1
160549
260949
111049
1
160550
260950
111050
1
160551
260951
111051
1
160552
260952
111052
1
160553
260953
111053
1
160554
260954
111054
1
160555
260955
111055
1
160556
260956
111056
1
160557
260957
111057
1
160558
260958
111058
1
160559
260959
111059
1
160560
260960
111060
1
160561
260961
111061
1
160562
260962
111062
1
160563
260963
111063
1
160564
260964
111064
1
160565
260965
111065
1
160566
260966
111066
1
160567
260967
111067
1
160568
260968
111068
1
160569
260969
111069
1
75
160570
260970
111070
1
160571
260971
111071
1
160572
260972
111072
1
160573
260973
111073
1
160574
260974
111074
1
160575
260975
111075
1
160576
260976
111076
1
160577
260977
111077
1
160578
260978
111078
1
160579
260979
111079
1
160580
260980
111080
1
160581
260981
111081
1
160582
260982
111082
1
160583
260983
111083
1
***
RECORD
12
***
Application:
aerial
Application
8
apps
@
2
lb
a.
i./
acre
***
RECORD
13
***
288
1
0
0
***
RECORD
15
***
Carbaryl
Chemical
Kd:
3.0
(Silt
Loam
Soil);
ASM
T1/
2
=
12
days;
AnSM
T1/
2
=
24
days
***
RECORD
16
***
300448
0
2
0.00
2.24
0.95
0.16
140548
0
2
0.00
2.24
0.95
0.16
280548
0
2
0.00
2.24
0.95
0.16
110648
0
2
0.00
2.24
0.95
0.16
250648
0
2
0.00
2.24
0.95
0.16
090748
0
2
0.00
2.24
0.95
0.16
230748
0
2
0.00
2.24
0.95
0.16
060848
0
2
0.00
2.24
0.95
0.16
300449
0
2
0.00
2.24
0.95
0.16
140549
0
2
0.00
2.24
0.95
0.16
280549
0
2
0.00
2.24
0.95
0.16
110649
0
2
0.00
2.24
0.95
0.16
250649
0
2
0.00
2.24
0.95
0.16
090749
0
2
0.00
2.24
0.95
0.16
230749
0
2
0.00
2.24
0.95
0.16
060849
0
2
0.00
2.24
0.95
0.16
300450
0
2
0.00
2.24
0.95
0.16
140550
0
2
0.00
2.24
0.95
0.16
280550
0
2
0.00
2.24
0.95
0.16
110650
0
2
0.00
2.24
0.95
0.16
250650
0
2
0.00
2.24
0.95
0.16
090750
0
2
0.00
2.24
0.95
0.16
230750
0
2
0.00
2.24
0.95
0.16
060850
0
2
0.00
2.24
0.95
0.16
300451
0
2
0.00
2.24
0.95
0.16
140551
0
2
0.00
2.24
0.95
0.16
280551
0
2
0.00
2.24
0.95
0.16
110651
0
2
0.00
2.24
0.95
0.16
250651
0
2
0.00
2.24
0.95
0.16
090751
0
2
0.00
2.24
0.95
0.16
230751
0
2
0.00
2.24
0.95
0.16
060851
0
2
0.00
2.24
0.95
0.16
300452
0
2
0.00
2.24
0.95
0.16
140552
0
2
0.00
2.24
0.95
0.16
280552
0
2
0.00
2.24
0.95
0.16
110652
0
2
0.00
2.24
0.95
0.16
250652
0
2
0.00
2.24
0.95
0.16
090752
0
2
0.00
2.24
0.95
0.16
230752
0
2
0.00
2.24
0.95
0.16
76
060852
0
2
0.00
2.24
0.95
0.16
300453
0
2
0.00
2.24
0.95
0.16
140553
0
2
0.00
2.24
0.95
0.16
280553
0
2
0.00
2.24
0.95
0.16
110653
0
2
0.00
2.24
0.95
0.16
250653
0
2
0.00
2.24
0.95
0.16
090753
0
2
0.00
2.24
0.95
0.16
230753
0
2
0.00
2.24
0.95
0.16
060853
0
2
0.00
2.24
0.95
0.16
300454
0
2
0.00
2.24
0.95
0.16
140554
0
2
0.00
2.24
0.95
0.16
280554
0
2
0.00
2.24
0.95
0.16
110654
0
2
0.00
2.24
0.95
0.16
250654
0
2
0.00
2.24
0.95
0.16
090754
0
2
0.00
2.24
0.95
0.16
230754
0
2
0.00
2.24
0.95
0.16
060854
0
2
0.00
2.24
0.95
0.16
300455
0
2
0.00
2.24
0.95
0.16
140555
0
2
0.00
2.24
0.95
0.16
280555
0
2
0.00
2.24
0.95
0.16
110655
0
2
0.00
2.24
0.95
0.16
250655
0
2
0.00
2.24
0.95
0.16
090755
0
2
0.00
2.24
0.95
0.16
230755
0
2
0.00
2.24
0.95
0.16
060855
0
2
0.00
2.24
0.95
0.16
300456
0
2
0.00
2.24
0.95
0.16
140556
0
2
0.00
2.24
0.95
0.16
280556
0
2
0.00
2.24
0.95
0.16
110656
0
2
0.00
2.24
0.95
0.16
250656
0
2
0.00
2.24
0.95
0.16
090756
0
2
0.00
2.24
0.95
0.16
230756
0
2
0.00
2.24
0.95
0.16
060856
0
2
0.00
2.24
0.95
0.16
300457
0
2
0.00
2.24
0.95
0.16
140557
0
2
0.00
2.24
0.95
0.16
280557
0
2
0.00
2.24
0.95
0.16
110657
0
2
0.00
2.24
0.95
0.16
250657
0
2
0.00
2.24
0.95
0.16
090757
0
2
0.00
2.24
0.95
0.16
230757
0
2
0.00
2.24
0.95
0.16
060857
0
2
0.00
2.24
0.95
0.16
300458
0
2
0.00
2.24
0.95
0.16
140558
0
2
0.00
2.24
0.95
0.16
280558
0
2
0.00
2.24
0.95
0.16
110658
0
2
0.00
2.24
0.95
0.16
250658
0
2
0.00
2.24
0.95
0.16
090758
0
2
0.00
2.24
0.95
0.16
230758
0
2
0.00
2.24
0.95
0.16
060858
0
2
0.00
2.24
0.95
0.16
300459
0
2
0.00
2.24
0.95
0.16
140559
0
2
0.00
2.24
0.95
0.16
280559
0
2
0.00
2.24
0.95
0.16
110659
0
2
0.00
2.24
0.95
0.16
250659
0
2
0.00
2.24
0.95
0.16
090759
0
2
0.00
2.24
0.95
0.16
230759
0
2
0.00
2.24
0.95
0.16
060859
0
2
0.00
2.24
0.95
0.16
300460
0
2
0.00
2.24
0.95
0.16
140560
0
2
0.00
2.24
0.95
0.16
280560
0
2
0.00
2.24
0.95
0.16
110660
0
2
0.00
2.24
0.95
0.16
77
250660
0
2
0.00
2.24
0.95
0.16
090760
0
2
0.00
2.24
0.95
0.16
230760
0
2
0.00
2.24
0.95
0.16
060860
0
2
0.00
2.24
0.95
0.16
300461
0
2
0.00
2.24
0.95
0.16
140561
0
2
0.00
2.24
0.95
0.16
280561
0
2
0.00
2.24
0.95
0.16
110661
0
2
0.00
2.24
0.95
0.16
250661
0
2
0.00
2.24
0.95
0.16
090761
0
2
0.00
2.24
0.95
0.16
230761
0
2
0.00
2.24
0.95
0.16
060861
0
2
0.00
2.24
0.95
0.16
300462
0
2
0.00
2.24
0.95
0.16
140562
0
2
0.00
2.24
0.95
0.16
280562
0
2
0.00
2.24
0.95
0.16
110662
0
2
0.00
2.24
0.95
0.16
250662
0
2
0.00
2.24
0.95
0.16
090762
0
2
0.00
2.24
0.95
0.16
230762
0
2
0.00
2.24
0.95
0.16
060862
0
2
0.00
2.24
0.95
0.16
300463
0
2
0.00
2.24
0.95
0.16
140563
0
2
0.00
2.24
0.95
0.16
280563
0
2
0.00
2.24
0.95
0.16
110663
0
2
0.00
2.24
0.95
0.16
250663
0
2
0.00
2.24
0.95
0.16
090763
0
2
0.00
2.24
0.95
0.16
230763
0
2
0.00
2.24
0.95
0.16
060863
0
2
0.00
2.24
0.95
0.16
300464
0
2
0.00
2.24
0.95
0.16
140564
0
2
0.00
2.24
0.95
0.16
280564
0
2
0.00
2.24
0.95
0.16
110664
0
2
0.00
2.24
0.95
0.16
250664
0
2
0.00
2.24
0.95
0.16
090764
0
2
0.00
2.24
0.95
0.16
230764
0
2
0.00
2.24
0.95
0.16
060864
0
2
0.00
2.24
0.95
0.16
300465
0
2
0.00
2.24
0.95
0.16
140565
0
2
0.00
2.24
0.95
0.16
280565
0
2
0.00
2.24
0.95
0.16
110665
0
2
0.00
2.24
0.95
0.16
250665
0
2
0.00
2.24
0.95
0.16
090765
0
2
0.00
2.24
0.95
0.16
230765
0
2
0.00
2.24
0.95
0.16
060865
0
2
0.00
2.24
0.95
0.16
300466
0
2
0.00
2.24
0.95
0.16
140566
0
2
0.00
2.24
0.95
0.16
280566
0
2
0.00
2.24
0.95
0.16
110666
0
2
0.00
2.24
0.95
0.16
250666
0
2
0.00
2.24
0.95
0.16
090766
0
2
0.00
2.24
0.95
0.16
230766
0
2
0.00
2.24
0.95
0.16
060866
0
2
0.00
2.24
0.95
0.16
300467
0
2
0.00
2.24
0.95
0.16
140567
0
2
0.00
2.24
0.95
0.16
280567
0
2
0.00
2.24
0.95
0.16
110667
0
2
0.00
2.24
0.95
0.16
250667
0
2
0.00
2.24
0.95
0.16
090767
0
2
0.00
2.24
0.95
0.16
230767
0
2
0.00
2.24
0.95
0.16
060867
0
2
0.00
2.24
0.95
0.16
300468
0
2
0.00
2.24
0.95
0.16
78
140568
0
2
0.00
2.24
0.95
0.16
280568
0
2
0.00
2.24
0.95
0.16
110668
0
2
0.00
2.24
0.95
0.16
250668
0
2
0.00
2.24
0.95
0.16
090768
0
2
0.00
2.24
0.95
0.16
230768
0
2
0.00
2.24
0.95
0.16
060868
0
2
0.00
2.24
0.95
0.16
300469
0
2
0.00
2.24
0.95
0.16
140569
0
2
0.00
2.24
0.95
0.16
280569
0
2
0.00
2.24
0.95
0.16
110669
0
2
0.00
2.24
0.95
0.16
250669
0
2
0.00
2.24
0.95
0.16
090769
0
2
0.00
2.24
0.95
0.16
230769
0
2
0.00
2.24
0.95
0.16
060869
0
2
0.00
2.24
0.95
0.16
300470
0
2
0.00
2.24
0.95
0.16
140570
0
2
0.00
2.24
0.95
0.16
280570
0
2
0.00
2.24
0.95
0.16
110670
0
2
0.00
2.24
0.95
0.16
250670
0
2
0.00
2.24
0.95
0.16
090770
0
2
0.00
2.24
0.95
0.16
230770
0
2
0.00
2.24
0.95
0.16
060870
0
2
0.00
2.24
0.95
0.16
300471
0
2
0.00
2.24
0.95
0.16
140571
0
2
0.00
2.24
0.95
0.16
280571
0
2
0.00
2.24
0.95
0.16
110671
0
2
0.00
2.24
0.95
0.16
250671
0
2
0.00
2.24
0.95
0.16
090771
0
2
0.00
2.24
0.95
0.16
230771
0
2
0.00
2.24
0.95
0.16
060871
0
2
0.00
2.24
0.95
0.16
300472
0
2
0.00
2.24
0.95
0.16
140572
0
2
0.00
2.24
0.95
0.16
280572
0
2
0.00
2.24
0.95
0.16
110672
0
2
0.00
2.24
0.95
0.16
250672
0
2
0.00
2.24
0.95
0.16
090772
0
2
0.00
2.24
0.95
0.16
230772
0
2
0.00
2.24
0.95
0.16
060872
0
2
0.00
2.24
0.95
0.16
300473
0
2
0.00
2.24
0.95
0.16
140573
0
2
0.00
2.24
0.95
0.16
280573
0
2
0.00
2.24
0.95
0.16
110673
0
2
0.00
2.24
0.95
0.16
250673
0
2
0.00
2.24
0.95
0.16
090773
0
2
0.00
2.24
0.95
0.16
230773
0
2
0.00
2.24
0.95
0.16
060873
0
2
0.00
2.24
0.95
0.16
300474
0
2
0.00
2.24
0.95
0.16
140574
0
2
0.00
2.24
0.95
0.16
280574
0
2
0.00
2.24
0.95
0.16
110674
0
2
0.00
2.24
0.95
0.16
250674
0
2
0.00
2.24
0.95
0.16
090774
0
2
0.00
2.24
0.95
0.16
230774
0
2
0.00
2.24
0.95
0.16
060874
0
2
0.00
2.24
0.95
0.16
300475
0
2
0.00
2.24
0.95
0.16
140575
0
2
0.00
2.24
0.95
0.16
280575
0
2
0.00
2.24
0.95
0.16
110675
0
2
0.00
2.24
0.95
0.16
250675
0
2
0.00
2.24
0.95
0.16
090775
0
2
0.00
2.24
0.95
0.16
79
230775
0
2
0.00
2.24
0.95
0.16
060875
0
2
0.00
2.24
0.95
0.16
300476
0
2
0.00
2.24
0.95
0.16
140576
0
2
0.00
2.24
0.95
0.16
280576
0
2
0.00
2.24
0.95
0.16
110676
0
2
0.00
2.24
0.95
0.16
250676
0
2
0.00
2.24
0.95
0.16
090776
0
2
0.00
2.24
0.95
0.16
230776
0
2
0.00
2.24
0.95
0.16
060876
0
2
0.00
2.24
0.95
0.16
300477
0
2
0.00
2.24
0.95
0.16
140577
0
2
0.00
2.24
0.95
0.16
280577
0
2
0.00
2.24
0.95
0.16
110677
0
2
0.00
2.24
0.95
0.16
250677
0
2
0.00
2.24
0.95
0.16
090777
0
2
0.00
2.24
0.95
0.16
230777
0
2
0.00
2.24
0.95
0.16
060877
0
2
0.00
2.24
0.95
0.16
300478
0
2
0.00
2.24
0.95
0.16
140578
0
2
0.00
2.24
0.95
0.16
280578
0
2
0.00
2.24
0.95
0.16
110678
0
2
0.00
2.24
0.95
0.16
250678
0
2
0.00
2.24
0.95
0.16
090778
0
2
0.00
2.24
0.95
0.16
230778
0
2
0.00
2.24
0.95
0.16
060878
0
2
0.00
2.24
0.95
0.16
300479
0
2
0.00
2.24
0.95
0.16
140579
0
2
0.00
2.24
0.95
0.16
280579
0
2
0.00
2.24
0.95
0.16
110679
0
2
0.00
2.24
0.95
0.16
250679
0
2
0.00
2.24
0.95
0.16
090779
0
2
0.00
2.24
0.95
0.16
230779
0
2
0.00
2.24
0.95
0.16
060879
0
2
0.00
2.24
0.95
0.16
300480
0
2
0.00
2.24
0.95
0.16
140580
0
2
0.00
2.24
0.95
0.16
280580
0
2
0.00
2.24
0.95
0.16
110680
0
2
0.00
2.24
0.95
0.16
250680
0
2
0.00
2.24
0.95
0.16
090780
0
2
0.00
2.24
0.95
0.16
230780
0
2
0.00
2.24
0.95
0.16
060880
0
2
0.00
2.24
0.95
0.16
300481
0
2
0.00
2.24
0.95
0.16
140581
0
2
0.00
2.24
0.95
0.16
280581
0
2
0.00
2.24
0.95
0.16
110681
0
2
0.00
2.24
0.95
0.16
250681
0
2
0.00
2.24
0.95
0.16
090781
0
2
0.00
2.24
0.95
0.16
230781
0
2
0.00
2.24
0.95
0.16
060881
0
2
0.00
2.24
0.95
0.16
300482
0
2
0.00
2.24
0.95
0.16
140582
0
2
0.00
2.24
0.95
0.16
280582
0
2
0.00
2.24
0.95
0.16
110682
0
2
0.00
2.24
0.95
0.16
250682
0
2
0.00
2.24
0.95
0.16
090782
0
2
0.00
2.24
0.95
0.16
230782
0
2
0.00
2.24
0.95
0.16
060882
0
2
0.00
2.24
0.95
0.16
300483
0
2
0.00
2.24
0.95
0.16
140583
0
2
0.00
2.24
0.95
0.16
280583
0
2
0.00
2.24
0.95
0.16
80
110683
0
2
0.00
2.24
0.95
0.16
250683
0
2
0.00
2.24
0.95
0.16
090783
0
2
0.00
2.24
0.95
0.16
230783
0
2
0.00
2.24
0.95
0.16
060883
0
2
0.00
2.24
0.95
0.16
***
Record
17
***
0.0
3
0
***
RECORD
18
***
0.0
0.0
0.00
***
RECORD
19
***
Soil
Series:
Cardington
silt
loam;
Hydrogic
Group
C
***
RECORD
20
***
100.00
0
0
0
0
0
0
0
0
0
***
RECORD
26
***
0.00
0.00
00.00
***
RECORD
33
***
2
***
RECORD
34,36,37
1
22.000
1.600
0.294
0.000
0.000
0.000
0.058
0.058
0.000
0.200
0.294
0.086
1.160
3.0
2
78.000
1.650
0.147
0.000
0.000
0.000
0.029
0.029
0.000
1.000
0.147
0.087
0.174
3.0
0
YEAR
10
YEAR
10
YEAR
10
1
1
1
7
YEAR
PRCP
TSER
0
0
RUNF
TSER
0
0
INFL
TSER
1
1
ESLS
TSER
0
0
1.
E3
RFLX
TSER
0
0
1.
E5
EFLX
TSER
0
0
1.
E5
RZFX
TSER
0
0
1.
E5
81
Average
Application
Rate
Ohio
Sweet
Corn,
Index
Reservoir
***
PRZM3
Input
File
for
INDEX
RESERVOIR,
IROHCORN1.
inp
converted
3/
30/
2000
***
***
Modeler:
S.
Abel
***
***
Modified
for
CARBARYL
by
Laurence
Libelo,
6/
20/
00
***
Use
rate
changed
to
QUA
(July
21,
1998
QUA
Report)
AVERAGE
VALUES
on
2/
28/
01
***
***
Manning's
N
values
for
cornstalk
residue,
fallow
surface,
1
ton/
acre
***
***
Cardington
silt
loam
is
not
one
of
the
benchmark
soils
***
***
Benchmark
soils
include:
blount;
crosby;
pewamo;
miami;
brookston;
glynwood
***
***
miamian;
morley;
bennington;
and
fincastle
***
***
IR
Spray
Drift:
Aerial:
0.16;
Orchard
air
blast:
0.063;
Ground
spray:
0.064
***
***
Application
efficiency:
0.95
aerial;
0.99
spray
blast
and
ground
spray
***
***
PCA
for
corn
=
0.46
***
CARBARYL
Location:
OH
Crop:
corn
MLRA
111
***
RECORD
3
***
0.72
0.30
0
15.00
1
3
***
RECORED
4
***
4
***
RECORD
7
***
0.37
0.43
0.50
172.8
5.80
3
6.00
600.0
***
RECORD
8
***
1
***
RECORD
9
***
1
0.25
90.00
100.00
3
91
85
88
0.00
100.00
***
RECORD
9A
***
1
3
***
RECORD
9B,
C,
D
0101
1605
1110
0.50
0.25
0.30
0.02
0.02
0.02
***
RECORD
10
***
36
***
RECORD
11
*
160548
260948
111048
1
160549
260949
111049
1
160550
260950
111050
1
160551
260951
111051
1
160552
260952
111052
1
160553
260953
111053
1
160554
260954
111054
1
160555
260955
111055
1
160556
260956
111056
1
160557
260957
111057
1
160558
260958
111058
1
160559
260959
111059
1
160560
260960
111060
1
160561
260961
111061
1
160562
260962
111062
1
160563
260963
111063
1
160564
260964
111064
1
160565
260965
111065
1
160566
260966
111066
1
160567
260967
111067
1
160568
260968
111068
1
160569
260969
111069
1
82
160570
260970
111070
1
160571
260971
111071
1
160572
260972
111072
1
160573
260973
111073
1
160574
260974
111074
1
160575
260975
111075
1
160576
260976
111076
1
160577
260977
111077
1
160578
260978
111078
1
160579
260979
111079
1
160580
260980
111080
1
160581
260981
111081
1
160582
260982
111082
1
160583
260983
111083
1
***
RECORD
12
***
Application
by
ground
spray
Rate
=
"average"
from
QUA
memo
(July
21,
1998)
3
apps
@
1.1
lb
a.
i./
acre
***
Application:
X
Application
Method.
2
apps
@
8
lb
a.
i./
acre
(8.9
kgs/
hectare
***
RECORD
13
***
108
1
0
0
***
RECORD
15
***
Carbaryl
Chemical
Kd:
3.0
(Silt
Loam
Soil);
ASM
T1/
2
=
12
days;
AnSM
T1/
2
=
24
days
***
RECORD
16
***
300448
0
2
0.00
1.23
0.95
0.064
140548
0
2
0.00
1.23
0.95
0.064
280548
0
2
0.00
1.23
0.95
0.064
300449
0
2
0.00
1.23
0.95
0.064
140549
0
2
0.00
1.23
0.95
0.064
280549
0
2
0.00
1.23
0.95
0.064
300450
0
2
0.00
1.23
0.95
0.064
140550
0
2
0.00
1.23
0.95
0.064
280550
0
2
0.00
1.23
0.95
0.064
300451
0
2
0.00
1.23
0.95
0.064
140551
0
2
0.00
1.23
0.95
0.064
280551
0
2
0.00
1.23
0.95
0.064
300452
0
2
0.00
1.23
0.95
0.064
140552
0
2
0.00
1.23
0.95
0.064
280552
0
2
0.00
1.23
0.95
0.064
300453
0
2
0.00
1.23
0.95
0.064
140553
0
2
0.00
1.23
0.95
0.064
280553
0
2
0.00
1.23
0.95
0.064
300454
0
2
0.00
1.23
0.95
0.064
140554
0
2
0.00
1.23
0.95
0.064
280554
0
2
0.00
1.23
0.95
0.064
300455
0
2
0.00
1.23
0.95
0.064
140555
0
2
0.00
1.23
0.95
0.064
280555
0
2
0.00
1.23
0.95
0.064
300456
0
2
0.00
1.23
0.95
0.064
140556
0
2
0.00
1.23
0.95
0.064
280556
0
2
0.00
1.23
0.95
0.064
300457
0
2
0.00
1.23
0.95
0.064
140557
0
2
0.00
1.23
0.95
0.064
280557
0
2
0.00
1.23
0.95
0.064
300458
0
2
0.00
1.23
0.95
0.064
140558
0
2
0.00
1.23
0.95
0.064
280558
0
2
0.00
1.23
0.95
0.064
300459
0
2
0.00
1.23
0.95
0.064
140559
0
2
0.00
1.23
0.95
0.064
280559
0
2
0.00
1.23
0.95
0.064
83
300460
0
2
0.00
1.23
0.95
0.064
140560
0
2
0.00
1.23
0.95
0.064
280560
0
2
0.00
1.23
0.95
0.064
300461
0
2
0.00
1.23
0.95
0.064
140561
0
2
0.00
1.23
0.95
0.064
280561
0
2
0.00
1.23
0.95
0.064
300462
0
2
0.00
1.23
0.95
0.064
140562
0
2
0.00
1.23
0.95
0.064
280562
0
2
0.00
1.23
0.95
0.064
300463
0
2
0.00
1.23
0.95
0.064
140563
0
2
0.00
1.23
0.95
0.064
280563
0
2
0.00
1.23
0.95
0.064
300464
0
2
0.00
1.23
0.95
0.064
140564
0
2
0.00
1.23
0.95
0.064
280564
0
2
0.00
1.23
0.95
0.064
300465
0
2
0.00
1.23
0.95
0.064
140565
0
2
0.00
1.23
0.95
0.064
280565
0
2
0.00
1.23
0.95
0.064
300466
0
2
0.00
1.23
0.95
0.064
140566
0
2
0.00
1.23
0.95
0.064
280566
0
2
0.00
1.23
0.95
0.064
300467
0
2
0.00
1.23
0.95
0.064
140567
0
2
0.00
1.23
0.95
0.064
280567
0
2
0.00
1.23
0.95
0.064
300468
0
2
0.00
1.23
0.95
0.064
140568
0
2
0.00
1.23
0.95
0.064
280568
0
2
0.00
1.23
0.95
0.064
300469
0
2
0.00
1.23
0.95
0.064
140569
0
2
0.00
1.23
0.95
0.064
280569
0
2
0.00
1.23
0.95
0.064
300470
0
2
0.00
1.23
0.95
0.064
140570
0
2
0.00
1.23
0.95
0.064
280570
0
2
0.00
1.23
0.95
0.064
300471
0
2
0.00
1.23
0.95
0.064
140571
0
2
0.00
1.23
0.95
0.064
280571
0
2
0.00
1.23
0.95
0.064
300472
0
2
0.00
1.23
0.95
0.064
140572
0
2
0.00
1.23
0.95
0.064
280572
0
2
0.00
1.23
0.95
0.064
300473
0
2
0.00
1.23
0.95
0.064
140573
0
2
0.00
1.23
0.95
0.064
280573
0
2
0.00
1.23
0.95
0.064
300474
0
2
0.00
1.23
0.95
0.064
140574
0
2
0.00
1.23
0.95
0.064
280574
0
2
0.00
1.23
0.95
0.064
300475
0
2
0.00
1.23
0.95
0.064
140575
0
2
0.00
1.23
0.95
0.064
280575
0
2
0.00
1.23
0.95
0.064
300476
0
2
0.00
1.23
0.95
0.064
140576
0
2
0.00
1.23
0.95
0.064
280576
0
2
0.00
1.23
0.95
0.064
300477
0
2
0.00
1.23
0.95
0.064
140577
0
2
0.00
1.23
0.95
0.064
280577
0
2
0.00
1.23
0.95
0.064
300478
0
2
0.00
1.23
0.95
0.064
140578
0
2
0.00
1.23
0.95
0.064
280578
0
2
0.00
1.23
0.95
0.064
300479
0
2
0.00
1.23
0.95
0.064
140579
0
2
0.00
1.23
0.95
0.064
280579
0
2
0.00
1.23
0.95
0.064
300480
0
2
0.00
1.23
0.95
0.064
84
140580
0
2
0.00
1.23
0.95
0.064
280580
0
2
0.00
1.23
0.95
0.064
300481
0
2
0.00
1.23
0.95
0.064
140581
0
2
0.00
1.23
0.95
0.064
280581
0
2
0.00
1.23
0.95
0.064
300482
0
2
0.00
1.23
0.95
0.064
140582
0
2
0.00
1.23
0.95
0.064
280582
0
2
0.00
1.23
0.95
0.064
300483
0
2
0.00
1.23
0.95
0.064
140583
0
2
0.00
1.23
0.95
0.064
280583
0
2
0.00
1.23
0.95
0.064
***
Record
17
***
0.0
3
0
***
RECORD
18
***
0.0
0.0
0.00
***
RECORD
19
***
Soil
Series:
Cardington
silt
loam;
Hydrogic
Group
C
***
RECORD
20
***
100.00
0
0
0
0
0
0
0
0
0
***
RECORD
26
***
0.00
0.00
00.00
***
RECORD
33
***
2
***
RECORD
34,36,37
1
22.000
1.600
0.294
0.000
0.000
0.000
0.058
0.058
0.000
0.200
0.294
0.086
1.160
3.0
2
78.000
1.650
0.147
0.000
0.000
0.000
0.029
0.029
0.000
1.000
0.147
0.087
0.174
3.0
0
YEAR
10
YEAR
10
YEAR
10
1
1
1
7
YEAR
PRCP
TSER
0
0
RUNF
TSER
0
0
INFL
TSER
1
1
ESLS
TSER
0
0
1.
E3
RFLX
TSER
0
0
1.
E5
EFLX
TSER
0
0
1.
E5
RZFX
TSER
0
0
1.
E5
85
Maximum
Reported
Application
Rate
Ohio
Sweet
Corn,
Index
Reservoir
***
PRZM3
Input
File
for
INDEX
RESERVOIR,
IROHCORN1.
inp
converted
3/
30/
2000
***
***
Modeler:
S.
Abel
***
***
Modified
for
CARBARYL
by
Laurence
Libelo,
6/
20/
00
***
Manning's
N
values
for
cornstalk
residue,
fallow
surface,
1
ton/
acre
***
***
Cardington
silt
loam
is
not
one
of
the
benchmark
soils
***
***
Benchmark
soils
include:
blount;
crosby;
pewamo;
miami;
brookston;
glynwood
***
***
miamian;
morley;
bennington;
and
fincastle
***
***
IR
Spray
Drift:
Aerial:
0.16;
Orchard
air
blast:
0.063;
Ground
spray:
0.064
***
***
Application
efficiency:
0.95
aerial;
0.99
spray
blast
and
ground
spray
***
***
PCA
for
corn
=
0.46
***
CARBARYL
Location:
OH
Crop:
corn
MLRA
111
***
RECORD
3
***
0.72
0.30
0
15.00
1
3
***
RECORED
4
***
4
***
RECORD
7
***
0.37
0.43
0.50
172.8
5.80
3
6.00
600.0
***
RECORD
8
***
1
***
RECORD
9
***
1
0.25
90.00
100.00
3
91
85
88
0.00
100.00
***
RECORD
9A
***
1
3
***
RECORD
9B,
C,
D
0101
1605
1110
0.50
0.25
0.30
0.02
0.02
0.02
***
RECORD
10
***
36
***
RECORD
11
*
160548
260948
111048
1
160549
260949
111049
1
160550
260950
111050
1
160551
260951
111051
1
160552
260952
111052
1
160553
260953
111053
1
160554
260954
111054
1
160555
260955
111055
1
160556
260956
111056
1
160557
260957
111057
1
160558
260958
111058
1
160559
260959
111059
1
86
160560
260960
111060
1
160561
260961
111061
1
160562
260962
111062
1
160563
260963
111063
1
160564
260964
111064
1
160565
260965
111065
1
160566
260966
111066
1
160567
260967
111067
1
160568
260968
111068
1
160569
260969
111069
1
160570
260970
111070
1
160571
260971
111071
1
160572
260972
111072
1
160573
260973
111073
1
160574
260974
111074
1
160575
260975
111075
1
160576
260976
111076
1
160577
260977
111077
1
160578
260978
111078
1
160579
260979
111079
1
160580
260980
111080
1
160581
260981
111081
1
160582
260982
111082
1
160583
260983
111083
1
***
RECORD
12
***
Max
reported
application
3
apps
@
1
lb
A.
I./
acre
***
Application:
aerial
Application
Method.
2
apps
@
8
lb
a.
i./
acre
(8.9
kgs/
hectare
***
RECORD
13
***
108
1
0
0
***
RECORD
15
***
Carbaryl
Chemical
Kd:
3.0
(Silt
Loam
Soil);
ASM
T1/
2
=
12
days;
AnSM
T1/
2
=
24
days
***
RECORD
16
***
300448
0
2
0.00
1.12
0.95
0.16
140548
0
2
0.00
1.12
0.95
0.16
280548
0
2
0.00
1.12
0.95
0.16
300449
0
2
0.00
1.12
0.95
0.16
140549
0
2
0.00
1.12
0.95
0.16
280549
0
2
0.00
1.12
0.95
0.16
300450
0
2
0.00
1.12
0.95
0.16
140550
0
2
0.00
1.12
0.95
0.16
280550
0
2
0.00
1.12
0.95
0.16
300451
0
2
0.00
1.12
0.95
0.16
140551
0
2
0.00
1.12
0.95
0.16
280551
0
2
0.00
1.12
0.95
0.16
300452
0
2
0.00
1.12
0.95
0.16
140552
0
2
0.00
1.12
0.95
0.16
280552
0
2
0.00
1.12
0.95
0.16
300453
0
2
0.00
1.12
0.95
0.16
140553
0
2
0.00
1.12
0.95
0.16
280553
0
2
0.00
1.12
0.95
0.16
87
300454
0
2
0.00
1.12
0.95
0.16
140554
0
2
0.00
1.12
0.95
0.16
280554
0
2
0.00
1.12
0.95
0.16
300455
0
2
0.00
1.12
0.95
0.16
140555
0
2
0.00
1.12
0.95
0.16
280555
0
2
0.00
1.12
0.95
0.16
300456
0
2
0.00
1.12
0.95
0.16
140556
0
2
0.00
1.12
0.95
0.16
280556
0
2
0.00
1.12
0.95
0.16
300457
0
2
0.00
1.12
0.95
0.16
140557
0
2
0.00
1.12
0.95
0.16
280557
0
2
0.00
1.12
0.95
0.16
300458
0
2
0.00
1.12
0.95
0.16
140558
0
2
0.00
1.12
0.95
0.16
280558
0
2
0.00
1.12
0.95
0.16
300459
0
2
0.00
1.12
0.95
0.16
140559
0
2
0.00
1.12
0.95
0.16
280559
0
2
0.00
1.12
0.95
0.16
300460
0
2
0.00
1.12
0.95
0.16
140560
0
2
0.00
1.12
0.95
0.16
280560
0
2
0.00
1.12
0.95
0.16
300461
0
2
0.00
1.12
0.95
0.16
140561
0
2
0.00
1.12
0.95
0.16
280561
0
2
0.00
1.12
0.95
0.16
300462
0
2
0.00
1.12
0.95
0.16
140562
0
2
0.00
1.12
0.95
0.16
280562
0
2
0.00
1.12
0.95
0.16
300463
0
2
0.00
1.12
0.95
0.16
140563
0
2
0.00
1.12
0.95
0.16
280563
0
2
0.00
1.12
0.95
0.16
300464
0
2
0.00
1.12
0.95
0.16
140564
0
2
0.00
1.12
0.95
0.16
280564
0
2
0.00
1.12
0.95
0.16
300465
0
2
0.00
1.12
0.95
0.16
140565
0
2
0.00
1.12
0.95
0.16
280565
0
2
0.00
1.12
0.95
0.16
300466
0
2
0.00
1.12
0.95
0.16
140566
0
2
0.00
1.12
0.95
0.16
280566
0
2
0.00
1.12
0.95
0.16
300467
0
2
0.00
1.12
0.95
0.16
140567
0
2
0.00
1.12
0.95
0.16
280567
0
2
0.00
1.12
0.95
0.16
300468
0
2
0.00
1.12
0.95
0.16
140568
0
2
0.00
1.12
0.95
0.16
280568
0
2
0.00
1.12
0.95
0.16
300469
0
2
0.00
1.12
0.95
0.16
140569
0
2
0.00
1.12
0.95
0.16
280569
0
2
0.00
1.12
0.95
0.16
300470
0
2
0.00
1.12
0.95
0.16
140570
0
2
0.00
1.12
0.95
0.16
280570
0
2
0.00
1.12
0.95
0.16
300471
0
2
0.00
1.12
0.95
0.16
88
140571
0
2
0.00
1.12
0.95
0.16
280571
0
2
0.00
1.12
0.95
0.16
300472
0
2
0.00
1.12
0.95
0.16
140572
0
2
0.00
1.12
0.95
0.16
280572
0
2
0.00
1.12
0.95
0.16
300473
0
2
0.00
1.12
0.95
0.16
140573
0
2
0.00
1.12
0.95
0.16
280573
0
2
0.00
1.12
0.95
0.16
300474
0
2
0.00
1.12
0.95
0.16
140574
0
2
0.00
1.12
0.95
0.16
280574
0
2
0.00
1.12
0.95
0.16
300475
0
2
0.00
1.12
0.95
0.16
140575
0
2
0.00
1.12
0.95
0.16
280575
0
2
0.00
1.12
0.95
0.16
300476
0
2
0.00
1.12
0.95
0.16
140576
0
2
0.00
1.12
0.95
0.16
280576
0
2
0.00
1.12
0.95
0.16
300477
0
2
0.00
1.12
0.95
0.16
140577
0
2
0.00
1.12
0.95
0.16
280577
0
2
0.00
1.12
0.95
0.16
300478
0
2
0.00
1.12
0.95
0.16
140578
0
2
0.00
1.12
0.95
0.16
280578
0
2
0.00
1.12
0.95
0.16
300479
0
2
0.00
1.12
0.95
0.16
140579
0
2
0.00
1.12
0.95
0.16
280579
0
2
0.00
1.12
0.95
0.16
300480
0
2
0.00
1.12
0.95
0.16
140580
0
2
0.00
1.12
0.95
0.16
280580
0
2
0.00
1.12
0.95
0.16
300481
0
2
0.00
1.12
0.95
0.16
140581
0
2
0.00
1.12
0.95
0.16
280581
0
2
0.00
1.12
0.95
0.16
300482
0
2
0.00
1.12
0.95
0.16
140582
0
2
0.00
1.12
0.95
0.16
280582
0
2
0.00
1.12
0.95
0.16
300483
0
2
0.00
1.12
0.95
0.16
140583
0
2
0.00
1.12
0.95
0.16
280583
0
2
0.00
1.12
0.95
0.16
***
Record
17
***
0.0
3
0
***
RECORD
18
***
0.0
0.0
0.00
***
RECORD
19
***
Soil
Series:
Cardington
silt
loam;
Hydrogic
Group
C
***
RECORD
20
***
100.00
0
0
0
0
0
0
0
0
0
***
RECORD
26
***
0.00
0.00
00.00
***
RECORD
33
***
2
***
RECORD
34,36,37
89
1
22.000
1.600
0.294
0.000
0.000
0.000
0.058
0.058
0.000
0.200
0.294
0.086
1.160
3.0
2
78.000
1.650
0.147
0.000
0.000
0.000
0.029
0.029
0.000
1.000
0.147
0.087
0.174
3.0
0
YEAR
10
YEAR
10
YEAR
10
1
1
1
7
YEAR
PRCP
TSER
0
0
RUNF
TSER
0
0
INFL
TSER
1
1
ESLS
TSER
0
0
1.
E3
RFLX
TSER
0
0
1.
E5
EFLX
TSER
0
0
1.
E5
RZFX
TSER
0
0
1.
E5
90
Maximum
Application
Rate
Ohio
Corn,
Index
Reservoir
***
PRZM3
Input
File
for
INDEX
RESERVOIR,
IROHCORN1.
inp
converted
3/
30/
2000
***
***
Modeler:
S.
Abel
***
***
Modified
for
CARBARYL
by
Laurence
Libelo,
6/
20/
00
***
Manning's
N
values
for
cornstalk
residue,
fallow
surface,
1
ton/
acre
***
***
Cardington
silt
loam
is
not
one
of
the
benchmark
soils
***
***
Benchmark
soils
include:
blount;
crosby;
pewamo;
miami;
brookston;
glynwood
***
***
miamian;
morley;
bennington;
and
fincastle
***
***
IR
Spray
Drift:
Aerial:
0.16;
Orchard
air
blast:
0.063;
Ground
spray:
0.064
***
***
Application
efficiency:
0.95
aerial;
0.99
spray
blast
and
ground
spray
***
***
PCA
for
corn
=
0.46
***
CARBARYL
Location:
OH
Crop:
corn
MLRA
111
***
RECORD
3
***
0.72
0.30
0
15.00
1
3
***
RECORED
4
***
4
***
RECORD
7
***
0.37
0.43
0.50
172.8
5.80
3
6.00
600.0
***
RECORD
8
***
1
***
RECORD
9
***
1
0.25
90.00
100.00
3
91
85
88
0.00
100.00
***
RECORD
9A
***
1
3
***
RECORD
9B,
C,
D
0101
1605
1110
0.50
0.25
0.30
0.02
0.02
0.02
***
RECORD
10
***
36
***
RECORD
11
*
160548
260948
111048
1
160549
260949
111049
1
160550
260950
111050
1
160551
260951
111051
1
160552
260952
111052
1
160553
260953
111053
1
160554
260954
111054
1
160555
260955
111055
1
160556
260956
111056
1
160557
260957
111057
1
160558
260958
111058
1
91
160559
260959
111059
1
160560
260960
111060
1
160561
260961
111061
1
160562
260962
111062
1
160563
260963
111063
1
160564
260964
111064
1
160565
260965
111065
1
160566
260966
111066
1
160567
260967
111067
1
160568
260968
111068
1
160569
260969
111069
1
160570
260970
111070
1
160571
260971
111071
1
160572
260972
111072
1
160573
260973
111073
1
160574
260974
111074
1
160575
260975
111075
1
160576
260976
111076
1
160577
260977
111077
1
160578
260978
111078
1
160579
260979
111079
1
160580
260980
111080
1
160581
260981
111081
1
160582
260982
111082
1
160583
260983
111083
1
***
RECORD
12
***
Application:
X
Application
Method.
4
apps
@
2
lb
a.
i./
acre
***
RECORD
13
***
144
1
0
0
***
RECORD
15
***
Carbaryl
Chemical
Kd:
3.0
(Silt
Loam
Soil);
ASM
T1/
2
=
12
days;
AnSM
T1/
2
=
24
days
***
RECORD
16
***
300448
0
2
0.00
2.24
0.95
0.16
140548
0
2
0.00
2.24
0.95
0.16
280548
0
2
0.00
2.24
0.95
0.16
110648
0
2
0.00
2.24
0.95
0.16
300449
0
2
0.00
2.24
0.95
0.16
140549
0
2
0.00
2.24
0.95
0.16
280549
0
2
0.00
2.24
0.95
0.16
110649
0
2
0.00
2.24
0.95
0.16
300450
0
2
0.00
2.24
0.95
0.16
140550
0
2
0.00
2.24
0.95
0.16
280550
0
2
0.00
2.24
0.95
0.16
110650
0
2
0.00
2.24
0.95
0.16
300451
0
2
0.00
2.24
0.95
0.16
140551
0
2
0.00
2.24
0.95
0.16
280551
0
2
0.00
2.24
0.95
0.16
110651
0
2
0.00
2.24
0.95
0.16
300452
0
2
0.00
2.24
0.95
0.16
92
140552
0
2
0.00
2.24
0.95
0.16
280552
0
2
0.00
2.24
0.95
0.16
110652
0
2
0.00
2.24
0.95
0.16
300453
0
2
0.00
2.24
0.95
0.16
140553
0
2
0.00
2.24
0.95
0.16
280553
0
2
0.00
2.24
0.95
0.16
110653
0
2
0.00
2.24
0.95
0.16
300454
0
2
0.00
2.24
0.95
0.16
140554
0
2
0.00
2.24
0.95
0.16
280554
0
2
0.00
2.24
0.95
0.16
110654
0
2
0.00
2.24
0.95
0.16
300455
0
2
0.00
2.24
0.95
0.16
140555
0
2
0.00
2.24
0.95
0.16
280555
0
2
0.00
2.24
0.95
0.16
110655
0
2
0.00
2.24
0.95
0.16
300456
0
2
0.00
2.24
0.95
0.16
140556
0
2
0.00
2.24
0.95
0.16
280556
0
2
0.00
2.24
0.95
0.16
110656
0
2
0.00
2.24
0.95
0.16
300457
0
2
0.00
2.24
0.95
0.16
140557
0
2
0.00
2.24
0.95
0.16
280557
0
2
0.00
2.24
0.95
0.16
110657
0
2
0.00
2.24
0.95
0.16
300458
0
2
0.00
2.24
0.95
0.16
140558
0
2
0.00
2.24
0.95
0.16
280558
0
2
0.00
2.24
0.95
0.16
110658
0
2
0.00
2.24
0.95
0.16
300459
0
2
0.00
2.24
0.95
0.16
140559
0
2
0.00
2.24
0.95
0.16
280559
0
2
0.00
2.24
0.95
0.16
110659
0
2
0.00
2.24
0.95
0.16
300460
0
2
0.00
2.24
0.95
0.16
140560
0
2
0.00
2.24
0.95
0.16
280560
0
2
0.00
2.24
0.95
0.16
110660
0
2
0.00
2.24
0.95
0.16
300461
0
2
0.00
2.24
0.95
0.16
140561
0
2
0.00
2.24
0.95
0.16
280561
0
2
0.00
2.24
0.95
0.16
110661
0
2
0.00
2.24
0.95
0.16
300462
0
2
0.00
2.24
0.95
0.16
140562
0
2
0.00
2.24
0.95
0.16
280562
0
2
0.00
2.24
0.95
0.16
110662
0
2
0.00
2.24
0.95
0.16
300463
0
2
0.00
2.24
0.95
0.16
140563
0
2
0.00
2.24
0.95
0.16
280563
0
2
0.00
2.24
0.95
0.16
110663
0
2
0.00
2.24
0.95
0.16
300464
0
2
0.00
2.24
0.95
0.16
140564
0
2
0.00
2.24
0.95
0.16
280564
0
2
0.00
2.24
0.95
0.16
93
110664
0
2
0.00
2.24
0.95
0.16
300465
0
2
0.00
2.24
0.95
0.16
140565
0
2
0.00
2.24
0.95
0.16
280565
0
2
0.00
2.24
0.95
0.16
110665
0
2
0.00
2.24
0.95
0.16
300466
0
2
0.00
2.24
0.95
0.16
140566
0
2
0.00
2.24
0.95
0.16
280566
0
2
0.00
2.24
0.95
0.16
110666
0
2
0.00
2.24
0.95
0.16
300467
0
2
0.00
2.24
0.95
0.16
140567
0
2
0.00
2.24
0.95
0.16
280567
0
2
0.00
2.24
0.95
0.16
110667
0
2
0.00
2.24
0.95
0.16
300468
0
2
0.00
2.24
0.95
0.16
140568
0
2
0.00
2.24
0.95
0.16
280568
0
2
0.00
2.24
0.95
0.16
110668
0
2
0.00
2.24
0.95
0.16
300469
0
2
0.00
2.24
0.95
0.16
140569
0
2
0.00
2.24
0.95
0.16
280569
0
2
0.00
2.24
0.95
0.16
110669
0
2
0.00
2.24
0.95
0.16
300470
0
2
0.00
2.24
0.95
0.16
140570
0
2
0.00
2.24
0.95
0.16
280570
0
2
0.00
2.24
0.95
0.16
110670
0
2
0.00
2.24
0.95
0.16
300471
0
2
0.00
2.24
0.95
0.16
140571
0
2
0.00
2.24
0.95
0.16
280571
0
2
0.00
2.24
0.95
0.16
110671
0
2
0.00
2.24
0.95
0.16
300472
0
2
0.00
2.24
0.95
0.16
140572
0
2
0.00
2.24
0.95
0.16
280572
0
2
0.00
2.24
0.95
0.16
110672
0
2
0.00
2.24
0.95
0.16
300473
0
2
0.00
2.24
0.95
0.16
140573
0
2
0.00
2.24
0.95
0.16
280573
0
2
0.00
2.24
0.95
0.16
110673
0
2
0.00
2.24
0.95
0.16
300474
0
2
0.00
2.24
0.95
0.16
140574
0
2
0.00
2.24
0.95
0.16
280574
0
2
0.00
2.24
0.95
0.16
110674
0
2
0.00
2.24
0.95
0.16
300475
0
2
0.00
2.24
0.95
0.16
140575
0
2
0.00
2.24
0.95
0.16
280575
0
2
0.00
2.24
0.95
0.16
110675
0
2
0.00
2.24
0.95
0.16
300476
0
2
0.00
2.24
0.95
0.16
140576
0
2
0.00
2.24
0.95
0.16
280576
0
2
0.00
2.24
0.95
0.16
110676
0
2
0.00
2.24
0.95
0.16
300477
0
2
0.00
2.24
0.95
0.16
94
140577
0
2
0.00
2.24
0.95
0.16
280577
0
2
0.00
2.24
0.95
0.16
110677
0
2
0.00
2.24
0.95
0.16
300478
0
2
0.00
2.24
0.95
0.16
140578
0
2
0.00
2.24
0.95
0.16
280578
0
2
0.00
2.24
0.95
0.16
110678
0
2
0.00
2.24
0.95
0.16
300479
0
2
0.00
2.24
0.95
0.16
140579
0
2
0.00
2.24
0.95
0.16
280579
0
2
0.00
2.24
0.95
0.16
110679
0
2
0.00
2.24
0.95
0.16
300480
0
2
0.00
2.24
0.95
0.16
140580
0
2
0.00
2.24
0.95
0.16
280580
0
2
0.00
2.24
0.95
0.16
110680
0
2
0.00
2.24
0.95
0.16
300481
0
2
0.00
2.24
0.95
0.16
140581
0
2
0.00
2.24
0.95
0.16
280581
0
2
0.00
2.24
0.95
0.16
110681
0
2
0.00
2.24
0.95
0.16
300482
0
2
0.00
2.24
0.95
0.16
140582
0
2
0.00
2.24
0.95
0.16
280582
0
2
0.00
2.24
0.95
0.16
110682
0
2
0.00
2.24
0.95
0.16
300483
0
2
0.00
2.24
0.95
0.16
140583
0
2
0.00
2.24
0.95
0.16
280583
0
2
0.00
2.24
0.95
0.16
110683
0
2
0.00
2.24
0.95
0.16
***
Record
17
***
0.0
3
0
***
RECORD
18
***
0.0
0.0
0.00
***
RECORD
19
***
Soil
Series:
Cardington
silt
loam;
Hydrogic
Group
C
***
RECORD
20
***
100.00
0
0
0
0
0
0
0
0
0
***
RECORD
26
***
0.00
0.00
00.00
***
RECORD
33
***
2
***
RECORD
34,36,37
1
22.000
1.600
0.294
0.000
0.000
0.000
0.058
0.058
0.000
0.200
0.294
0.086
1.160
3.0
2
78.000
1.650
0.147
0.000
0.000
0.000
0.029
0.029
0.000
1.000
0.147
0.087
0.174
3.0
0
YEAR
10
YEAR
10
YEAR
10
1
95
1
1
7
YEAR
PRCP
TSER
0
0
RUNF
TSER
0
0
INFL
TSER
1
1
ESLS
TSER
0
0
1.
E3
RFLX
TSER
0
0
1.
E5
EFLX
TSER
0
0
1.
E5
RZFX
TSER
0
0
1.
E5
96
Average
Reported
Application
Rate
Ohio
Corn,
Index
Reservoir
***
PRZM3
Input
File
for
INDEX
RESERVOIR,
IROHCORN1.
inp
converted
3/
30/
2000
***
***
Modeler:
S.
Abel
***
***
Modified
for
CARBARYL
by
Laurence
Libelo,
6/
20/
00
***
Manning's
N
values
for
cornstalk
residue,
fallow
surface,
1
ton/
acre
***
***
Cardington
silt
loam
is
not
one
of
the
benchmark
soils
***
***
Benchmark
soils
include:
blount;
crosby;
pewamo;
miami;
brookston;
glynwood
***
***
miamian;
morley;
bennington;
and
fincastle
***
***
IR
Spray
Drift:
Aerial:
0.16;
Orchard
air
blast:
0.063;
Ground
spray:
0.064
***
***
Application
efficiency:
0.95
aerial;
0.99
spray
blast
and
ground
spray
***
***
PCA
for
corn
=
0.46
***
CARBARYL
Location:
OH
Crop:
corn
MLRA
111
***
RECORD
3
***
0.72
0.30
0
15.00
1
3
***
RECORED
4
***
4
***
RECORD
7
***
0.37
0.43
0.50
172.8
5.80
3
6.00
600.0
***
RECORD
8
***
1
***
RECORD
9
***
1
0.25
90.00
100.00
3
91
85
88
0.00
100.00
***
RECORD
9A
***
1
3
***
RECORD
9B,
C,
D
0101
1605
1110
0.50
0.25
0.30
0.02
0.02
0.02
***
RECORD
10
***
36
***
RECORD
11
*
160548
260948
111048
1
160549
260949
111049
1
160550
260950
111050
1
160551
260951
111051
1
160552
260952
111052
1
160553
260953
111053
1
160554
260954
111054
1
160555
260955
111055
1
160556
260956
111056
1
97
160557
260957
111057
1
160558
260958
111058
1
160559
260959
111059
1
160560
260960
111060
1
160561
260961
111061
1
160562
260962
111062
1
160563
260963
111063
1
160564
260964
111064
1
160565
260965
111065
1
160566
260966
111066
1
160567
260967
111067
1
160568
260968
111068
1
160569
260969
111069
1
160570
260970
111070
1
160571
260971
111071
1
160572
260972
111072
1
160573
260973
111073
1
160574
260974
111074
1
160575
260975
111075
1
160576
260976
111076
1
160577
260977
111077
1
160578
260978
111078
1
160579
260979
111079
1
160580
260980
111080
1
160581
260981
111081
1
160582
260982
111082
1
160583
260983
111083
1
***
RECORD
12
***
Average
app
rate
2
apps
@
1
lb
A.
I./
acre
***
Application:
aerial
Application
at
max
label
rate
4
apps
@
2
lb
a.
i./
acre
***
RECORD
13
***
72
1
0
0
***
RECORD
15
***
Carbaryl
Chemical
Kd:
3.0
(Silt
Loam
Soil);
ASM
T1/
2
=
12
days;
AnSM
T1/
2
=
24
days
***
RECORD
16
***
300448
0
2
0.00
1.12
0.95
0.16
140548
0
2
0.00
1.12
0.95
0.16
300449
0
2
0.00
1.12
0.95
0.16
140549
0
2
0.00
1.12
0.95
0.16
300450
0
2
0.00
1.12
0.95
0.16
140550
0
2
0.00
1.12
0.95
0.16
300451
0
2
0.00
1.12
0.95
0.16
140551
0
2
0.00
1.12
0.95
0.16
300452
0
2
0.00
1.12
0.95
0.16
140552
0
2
0.00
1.12
0.95
0.16
300453
0
2
0.00
1.12
0.95
0.16
140553
0
2
0.00
1.12
0.95
0.16
300454
0
2
0.00
1.12
0.95
0.16
98
140554
0
2
0.00
1.12
0.95
0.16
300455
0
2
0.00
1.12
0.95
0.16
140555
0
2
0.00
1.12
0.95
0.16
300456
0
2
0.00
1.12
0.95
0.16
140556
0
2
0.00
1.12
0.95
0.16
300457
0
2
0.00
1.12
0.95
0.16
140557
0
2
0.00
1.12
0.95
0.16
300458
0
2
0.00
1.12
0.95
0.16
140558
0
2
0.00
1.12
0.95
0.16
300459
0
2
0.00
1.12
0.95
0.16
140559
0
2
0.00
1.12
0.95
0.16
300460
0
2
0.00
1.12
0.95
0.16
140560
0
2
0.00
1.12
0.95
0.16
300461
0
2
0.00
1.12
0.95
0.16
140561
0
2
0.00
1.12
0.95
0.16
300462
0
2
0.00
1.12
0.95
0.16
140562
0
2
0.00
1.12
0.95
0.16
300463
0
2
0.00
1.12
0.95
0.16
140563
0
2
0.00
1.12
0.95
0.16
300464
0
2
0.00
1.12
0.95
0.16
140564
0
2
0.00
1.12
0.95
0.16
300465
0
2
0.00
1.12
0.95
0.16
140565
0
2
0.00
1.12
0.95
0.16
300466
0
2
0.00
1.12
0.95
0.16
140566
0
2
0.00
1.12
0.95
0.16
300467
0
2
0.00
1.12
0.95
0.16
140567
0
2
0.00
1.12
0.95
0.16
300468
0
2
0.00
1.12
0.95
0.16
140568
0
2
0.00
1.12
0.95
0.16
300469
0
2
0.00
1.12
0.95
0.16
140569
0
2
0.00
1.12
0.95
0.16
300470
0
2
0.00
1.12
0.95
0.16
140570
0
2
0.00
1.12
0.95
0.16
300471
0
2
0.00
1.12
0.95
0.16
140571
0
2
0.00
1.12
0.95
0.16
300472
0
2
0.00
1.12
0.95
0.16
140572
0
2
0.00
1.12
0.95
0.16
300473
0
2
0.00
1.12
0.95
0.16
140573
0
2
0.00
1.12
0.95
0.16
300474
0
2
0.00
1.12
0.95
0.16
140574
0
2
0.00
1.12
0.95
0.16
300475
0
2
0.00
1.12
0.95
0.16
140575
0
2
0.00
1.12
0.95
0.16
300476
0
2
0.00
1.12
0.95
0.16
140576
0
2
0.00
1.12
0.95
0.16
300477
0
2
0.00
1.12
0.95
0.16
140577
0
2
0.00
1.12
0.95
0.16
300478
0
2
0.00
1.12
0.95
0.16
140578
0
2
0.00
1.12
0.95
0.16
300479
0
2
0.00
1.12
0.95
0.16
99
140579
0
2
0.00
1.12
0.95
0.16
300480
0
2
0.00
1.12
0.95
0.16
140580
0
2
0.00
1.12
0.95
0.16
300481
0
2
0.00
1.12
0.95
0.16
140581
0
2
0.00
1.12
0.95
0.16
300482
0
2
0.00
1.12
0.95
0.16
140582
0
2
0.00
1.12
0.95
0.16
300483
0
2
0.00
1.12
0.95
0.16
140583
0
2
0.00
1.12
0.95
0.16
***
Record
17
***
0.0
3
0
***
RECORD
18
***
0.0
0.0
0.00
***
RECORD
19
***
Soil
Series:
Cardington
silt
loam;
Hydrogic
Group
C
***
RECORD
20
***
100.00
0
0
0
0
0
0
0
0
0
***
RECORD
26
***
0.00
0.00
00.00
***
RECORD
33
***
2
***
RECORD
34,36,37
1
22.000
1.600
0.294
0.000
0.000
0.000
0.058
0.058
0.000
0.200
0.294
0.086
1.160
3.0
2
78.000
1.650
0.147
0.000
0.000
0.000
0.029
0.029
0.000
1.000
0.147
0.087
0.174
3.0
0
YEAR
10
YEAR
10
YEAR
10
1
1
1
7
YEAR
PRCP
TSER
0
0
RUNF
TSER
0
0
INFL
TSER
1
1
ESLS
TSER
0
0
1.
E3
RFLX
TSER
0
0
1.
E5
EFLX
TSER
0
0
1.
E5
RZFX
TSER
0
0
1.
E5
100
Maximum
Reported
Application
Rate
Ohio
Corn,
Index
Reservoir
***
PRZM3
Input
File
for
INDEX
RESERVOIR,
IROHCORN1.
inp
converted
3/
30/
2000
***
***
Modeler:
S.
Abel
***
***
Modified
for
CARBARYL
by
Laurence
Libelo,
6/
20/
00
***
Manning's
N
values
for
cornstalk
residue,
fallow
surface,
1
ton/
acre
***
***
Cardington
silt
loam
is
not
one
of
the
benchmark
soils
***
***
Benchmark
soils
include:
blount;
crosby;
pewamo;
miami;
brookston;
glynwood
***
***
miamian;
morley;
bennington;
and
fincastle
***
***
IR
Spray
Drift:
Aerial:
0.16;
Orchard
air
blast:
0.063;
Ground
spray:
0.064
***
***
Application
efficiency:
0.95
aerial;
0.99
spray
blast
and
ground
spray
***
***
PCA
for
corn
=
0.46
***
CARBARYL
Location:
OH
Crop:
corn
MLRA
111
***
RECORD
3
***
0.72
0.30
0
15.00
1
3
***
RECORED
4
***
4
***
RECORD
7
***
0.37
0.43
0.50
172.8
5.80
3
6.00
600.0
***
RECORD
8
***
1
***
RECORD
9
***
1
0.25
90.00
100.00
3
91
85
88
0.00
100.00
***
RECORD
9A
***
1
3
***
RECORD
9B,
C,
D
0101
1605
1110
0.50
0.25
0.30
0.02
0.02
0.02
***
RECORD
10
***
36
***
RECORD
11
*
160548
260948
111048
1
160549
260949
111049
1
160550
260950
111050
1
160551
260951
111051
1
160552
260952
111052
1
160553
260953
111053
1
160554
260954
111054
1
160555
260955
111055
1
160556
260956
111056
1
160557
260957
111057
1
101
160558
260958
111058
1
160559
260959
111059
1
160560
260960
111060
1
160561
260961
111061
1
160562
260962
111062
1
160563
260963
111063
1
160564
260964
111064
1
160565
260965
111065
1
160566
260966
111066
1
160567
260967
111067
1
160568
260968
111068
1
160569
260969
111069
1
160570
260970
111070
1
160571
260971
111071
1
160572
260972
111072
1
160573
260973
111073
1
160574
260974
111074
1
160575
260975
111075
1
160576
260976
111076
1
160577
260977
111077
1
160578
260978
111078
1
160579
260979
111079
1
160580
260980
111080
1
160581
260981
111081
1
160582
260982
111082
1
160583
260983
111083
1
***
RECORD
12
***
Max
reported
app
rate
2
apps
@
1.5
lb
A.
I./
acre
***
Application:
aerial
Application
at
max
label
rate
4
apps
@
2
lb
a.
i./
acre
***
RECORD
13
***
72
1
0
0
***
RECORD
15
***
Carbaryl
Chemical
Kd:
3.0
(Silt
Loam
Soil);
ASM
T1/
2
=
12
days;
AnSM
T1/
2
=
24
days
***
RECORD
16
***
300448
0
2
0.00
1.68
0.95
0.16
140548
0
2
0.00
1.68
0.95
0.16
300449
0
2
0.00
1.68
0.95
0.16
140549
0
2
0.00
1.68
0.95
0.16
300450
0
2
0.00
1.68
0.95
0.16
140550
0
2
0.00
1.68
0.95
0.16
300451
0
2
0.00
1.68
0.95
0.16
140551
0
2
0.00
1.68
0.95
0.16
300452
0
2
0.00
1.68
0.95
0.16
140552
0
2
0.00
1.68
0.95
0.16
300453
0
2
0.00
1.68
0.95
0.16
140553
0
2
0.00
1.68
0.95
0.16
300454
0
2
0.00
1.68
0.95
0.16
140554
0
2
0.00
1.68
0.95
0.16
102
300455
0
2
0.00
1.68
0.95
0.16
140555
0
2
0.00
1.68
0.95
0.16
300456
0
2
0.00
1.68
0.95
0.16
140556
0
2
0.00
1.68
0.95
0.16
300457
0
2
0.00
1.68
0.95
0.16
140557
0
2
0.00
1.68
0.95
0.16
300458
0
2
0.00
1.68
0.95
0.16
140558
0
2
0.00
1.68
0.95
0.16
300459
0
2
0.00
1.68
0.95
0.16
140559
0
2
0.00
1.68
0.95
0.16
300460
0
2
0.00
1.68
0.95
0.16
140560
0
2
0.00
1.68
0.95
0.16
300461
0
2
0.00
1.68
0.95
0.16
140561
0
2
0.00
1.68
0.95
0.16
300462
0
2
0.00
1.68
0.95
0.16
140562
0
2
0.00
1.68
0.95
0.16
300463
0
2
0.00
1.68
0.95
0.16
140563
0
2
0.00
1.68
0.95
0.16
300464
0
2
0.00
1.68
0.95
0.16
140564
0
2
0.00
1.68
0.95
0.16
300465
0
2
0.00
1.68
0.95
0.16
140565
0
2
0.00
1.68
0.95
0.16
300466
0
2
0.00
1.68
0.95
0.16
140566
0
2
0.00
1.68
0.95
0.16
300467
0
2
0.00
1.68
0.95
0.16
140567
0
2
0.00
1.68
0.95
0.16
300468
0
2
0.00
1.68
0.95
0.16
140568
0
2
0.00
1.68
0.95
0.16
300469
0
2
0.00
1.68
0.95
0.16
140569
0
2
0.00
1.68
0.95
0.16
300470
0
2
0.00
1.68
0.95
0.16
140570
0
2
0.00
1.68
0.95
0.16
300471
0
2
0.00
1.68
0.95
0.16
140571
0
2
0.00
1.68
0.95
0.16
300472
0
2
0.00
1.68
0.95
0.16
140572
0
2
0.00
1.68
0.95
0.16
300473
0
2
0.00
1.68
0.95
0.16
140573
0
2
0.00
1.68
0.95
0.16
300474
0
2
0.00
1.68
0.95
0.16
140574
0
2
0.00
1.68
0.95
0.16
300475
0
2
0.00
1.68
0.95
0.16
140575
0
2
0.00
1.68
0.95
0.16
300476
0
2
0.00
1.68
0.95
0.16
140576
0
2
0.00
1.68
0.95
0.16
300477
0
2
0.00
1.68
0.95
0.16
140577
0
2
0.00
1.68
0.95
0.16
300478
0
2
0.00
1.68
0.95
0.16
140578
0
2
0.00
1.68
0.95
0.16
300479
0
2
0.00
1.68
0.95
0.16
140579
0
2
0.00
1.68
0.95
0.16
103
300480
0
2
0.00
1.68
0.95
0.16
140580
0
2
0.00
1.68
0.95
0.16
300481
0
2
0.00
1.68
0.95
0.16
140581
0
2
0.00
1.68
0.95
0.16
300482
0
2
0.00
1.68
0.95
0.16
140582
0
2
0.00
1.68
0.95
0.16
300483
0
2
0.00
1.68
0.95
0.16
140583
0
2
0.00
1.68
0.95
0.16
***
Record
17
***
0.0
3
0
***
RECORD
18
***
0.0
0.0
0.00
***
RECORD
19
***
Soil
Series:
Cardington
silt
loam;
Hydrogic
Group
C
***
RECORD
20
***
100.00
0
0
0
0
0
0
0
0
0
***
RECORD
26
***
0.00
0.00
00.00
***
RECORD
33
***
2
***
RECORD
34,36,37
1
22.000
1.600
0.294
0.000
0.000
0.000
0.058
0.058
0.000
0.200
0.294
0.086
1.160
3.0
2
78.000
1.650
0.147
0.000
0.000
0.000
0.029
0.029
0.000
1.000
0.147
0.087
0.174
3.0
0
YEAR
10
YEAR
10
YEAR
10
1
1
1
7
YEAR
PRCP
TSER
0
0
RUNF
TSER
0
0
INFL
TSER
1
1
ESLS
TSER
0
0
1.
E3
RFLX
TSER
0
0
1.
E5
EFLX
TSER
0
0
1.
E5
RZFX
TSER
0
0
1.
E5
104
Maximum
Application
Rate:
Oregon
Apples,
Index
Reservoir
***
PRZM
3.1
Input
Data
File;
ORAPPLEX.
INP;
Modified
April
5,
1998
***
***
Modified
for
Carbaryl
by
Laurence
Libelo,
6/
21/
00
***
Modified
for
Index
Res.
by
Laurence
Libelo,
3/
7/
01
***
Crops
simulated:
Apples,
Crabapples,
and
Quince
***
***
Location
Washington
County,
Oregon;
Meadow/
Orchard
Scenario;
MLRA:
A2
***
***
Manning's
N:
Assume
sparse
grass
under
mature
trees
(ca.
20
feet)
***
***
Temperature
data
read
***
***
This
file
is
for
scenario
standardization;
Reference
chemical
is
Atrazine
***
***
See
ORAPPLEX.
wpd
for
scenario
details
***
Carbaryl
Cornelius
silt
loam,
15%
slope,
Hydrologic
Group:
C
0.740
0.150
2
17.000
1
3
9.2
10.3
11.8
13.6
15.30
15.3
14.2
12.5
10.9
9.4
8.6
9.1
4
0.43
3.30
1.0
172.8
5.4
2
15.00
464
1
1
0.25
17.0
100.000
3
91
71
71
0.0
600
1
3
0103
0105
0112
0.01
0.01
0.01
0.015
0.015
0.015
36
010448
150548
151248
1
010449
150549
151249
1
010450
150550
151250
1
010451
150551
151251
1
010452
150552
151252
1
010453
150553
151253
1
010454
150554
151254
1
010455
150555
151255
1
010456
150556
151256
1
010457
150557
151257
1
010458
150558
151258
1
010459
150559
151259
1
010460
150560
151260
1
010461
150561
151261
1
010462
150562
151262
1
010463
150563
151263
1
010464
150564
151264
1
010465
150565
151265
1
010466
150566
151266
1
010467
150567
151267
1
105
010468
150568
151268
1
010469
150569
151269
1
010470
150570
151270
1
010471
150571
151271
1
010472
150572
151272
1
010473
150573
151273
1
010474
150574
151274
1
010475
150575
151275
1
010476
150576
151276
1
010477
150577
151277
1
010478
150578
151278
1
010479
150579
151279
1
010480
150580
151280
1
010481
150581
151281
1
010482
150582
151282
1
010483
150583
151283
1
Aerial
Application:
5
apps
of
2
lb
a.
i./
acre
(2.2
kg/
ha),
Aerial
@
95%
eff.
w/
16%
drift
180
1
0
0
Chemical
Kd:
3.0
(silt
Loam
soil);
AeSM:
T1/
2:
12
days;
AnSM:
T1/
2
=
24
days
***
Record
16:
Application
information;
set
specific
to
carbaryl
***
100348
0
2
0.00
2.24
0.95
0.16
140348
0
2
0.00
2.24
0.95
0.16
180348
0
2
0.00
2.24
0.95
0.16
220348
0
2
0.00
2.24
0.95
0.16
260348
0
2
0.00
2.24
0.95
0.16
100349
0
2
0.00
2.24
0.95
0.16
140349
0
2
0.00
2.24
0.95
0.16
180349
0
2
0.00
2.24
0.95
0.16
220349
0
2
0.00
2.24
0.95
0.16
260349
0
2
0.00
2.24
0.95
0.16
100350
0
2
0.00
2.24
0.95
0.16
140350
0
2
0.00
2.24
0.95
0.16
180350
0
2
0.00
2.24
0.95
0.16
220350
0
2
0.00
2.24
0.95
0.16
260350
0
2
0.00
2.24
0.95
0.16
100351
0
2
0.00
2.24
0.95
0.16
140351
0
2
0.00
2.24
0.95
0.16
180351
0
2
0.00
2.24
0.95
0.16
220351
0
2
0.00
2.24
0.95
0.16
260351
0
2
0.00
2.24
0.95
0.16
100352
0
2
0.00
2.24
0.95
0.16
140352
0
2
0.00
2.24
0.95
0.16
180352
0
2
0.00
2.24
0.95
0.16
220352
0
2
0.00
2.24
0.95
0.16
260352
0
2
0.00
2.24
0.95
0.16
100353
0
2
0.00
2.24
0.95
0.16
140353
0
2
0.00
2.24
0.95
0.16
106
180353
0
2
0.00
2.24
0.95
0.16
220353
0
2
0.00
2.24
0.95
0.16
260353
0
2
0.00
2.24
0.95
0.16
100354
0
2
0.00
2.24
0.95
0.16
140354
0
2
0.00
2.24
0.95
0.16
180354
0
2
0.00
2.24
0.95
0.16
220354
0
2
0.00
2.24
0.95
0.16
260354
0
2
0.00
2.24
0.95
0.16
100355
0
2
0.00
2.24
0.95
0.16
140355
0
2
0.00
2.24
0.95
0.16
180355
0
2
0.00
2.24
0.95
0.16
220355
0
2
0.00
2.24
0.95
0.16
260355
0
2
0.00
2.24
0.95
0.16
100356
0
2
0.00
2.24
0.95
0.16
140356
0
2
0.00
2.24
0.95
0.16
180356
0
2
0.00
2.24
0.95
0.16
220356
0
2
0.00
2.24
0.95
0.16
260356
0
2
0.00
2.24
0.95
0.16
100357
0
2
0.00
2.24
0.95
0.16
140357
0
2
0.00
2.24
0.95
0.16
180357
0
2
0.00
2.24
0.95
0.16
220357
0
2
0.00
2.24
0.95
0.16
260357
0
2
0.00
2.24
0.95
0.16
100358
0
2
0.00
2.24
0.95
0.16
140358
0
2
0.00
2.24
0.95
0.16
180358
0
2
0.00
2.24
0.95
0.16
220358
0
2
0.00
2.24
0.95
0.16
260358
0
2
0.00
2.24
0.95
0.16
100359
0
2
0.00
2.24
0.95
0.16
140359
0
2
0.00
2.24
0.95
0.16
180359
0
2
0.00
2.24
0.95
0.16
220359
0
2
0.00
2.24
0.95
0.16
260359
0
2
0.00
2.24
0.95
0.16
100360
0
2
0.00
2.24
0.95
0.16
140360
0
2
0.00
2.24
0.95
0.16
180360
0
2
0.00
2.24
0.95
0.16
220360
0
2
0.00
2.24
0.95
0.16
260360
0
2
0.00
2.24
0.95
0.16
100361
0
2
0.00
2.24
0.95
0.16
140361
0
2
0.00
2.24
0.95
0.16
180361
0
2
0.00
2.24
0.95
0.16
220361
0
2
0.00
2.24
0.95
0.16
260361
0
2
0.00
2.24
0.95
0.16
100362
0
2
0.00
2.24
0.95
0.16
140362
0
2
0.00
2.24
0.95
0.16
180362
0
2
0.00
2.24
0.95
0.16
220362
0
2
0.00
2.24
0.95
0.16
260362
0
2
0.00
2.24
0.95
0.16
100363
0
2
0.00
2.24
0.95
0.16
140363
0
2
0.00
2.24
0.95
0.16
107
180363
0
2
0.00
2.24
0.95
0.16
220363
0
2
0.00
2.24
0.95
0.16
260363
0
2
0.00
2.24
0.95
0.16
100364
0
2
0.00
2.24
0.95
0.16
140364
0
2
0.00
2.24
0.95
0.16
180364
0
2
0.00
2.24
0.95
0.16
220364
0
2
0.00
2.24
0.95
0.16
260364
0
2
0.00
2.24
0.95
0.16
100365
0
2
0.00
2.24
0.95
0.16
140365
0
2
0.00
2.24
0.95
0.16
180365
0
2
0.00
2.24
0.95
0.16
220365
0
2
0.00
2.24
0.95
0.16
260365
0
2
0.00
2.24
0.95
0.16
100366
0
2
0.00
2.24
0.95
0.16
140366
0
2
0.00
2.24
0.95
0.16
180366
0
2
0.00
2.24
0.95
0.16
220366
0
2
0.00
2.24
0.95
0.16
260366
0
2
0.00
2.24
0.95
0.16
100367
0
2
0.00
2.24
0.95
0.16
140367
0
2
0.00
2.24
0.95
0.16
180367
0
2
0.00
2.24
0.95
0.16
220367
0
2
0.00
2.24
0.95
0.16
260367
0
2
0.00
2.24
0.95
0.16
100368
0
2
0.00
2.24
0.95
0.16
140368
0
2
0.00
2.24
0.95
0.16
180368
0
2
0.00
2.24
0.95
0.16
220368
0
2
0.00
2.24
0.95
0.16
260368
0
2
0.00
2.24
0.95
0.16
100369
0
2
0.00
2.24
0.95
0.16
140369
0
2
0.00
2.24
0.95
0.16
180369
0
2
0.00
2.24
0.95
0.16
220369
0
2
0.00
2.24
0.95
0.16
260369
0
2
0.00
2.24
0.95
0.16
100370
0
2
0.00
2.24
0.95
0.16
140370
0
2
0.00
2.24
0.95
0.16
180370
0
2
0.00
2.24
0.95
0.16
220370
0
2
0.00
2.24
0.95
0.16
260370
0
2
0.00
2.24
0.95
0.16
100371
0
2
0.00
2.24
0.95
0.16
140371
0
2
0.00
2.24
0.95
0.16
180371
0
2
0.00
2.24
0.95
0.16
220371
0
2
0.00
2.24
0.95
0.16
260371
0
2
0.00
2.24
0.95
0.16
100372
0
2
0.00
2.24
0.95
0.16
140372
0
2
0.00
2.24
0.95
0.16
180372
0
2
0.00
2.24
0.95
0.16
220372
0
2
0.00
2.24
0.95
0.16
260372
0
2
0.00
2.24
0.95
0.16
100373
0
2
0.00
2.24
0.95
0.16
140373
0
2
0.00
2.24
0.95
0.16
108
180373
0
2
0.00
2.24
0.95
0.16
220373
0
2
0.00
2.24
0.95
0.16
260373
0
2
0.00
2.24
0.95
0.16
100374
0
2
0.00
2.24
0.95
0.16
140374
0
2
0.00
2.24
0.95
0.16
180374
0
2
0.00
2.24
0.95
0.16
220374
0
2
0.00
2.24
0.95
0.16
260374
0
2
0.00
2.24
0.95
0.16
100375
0
2
0.00
2.24
0.95
0.16
140375
0
2
0.00
2.24
0.95
0.16
180375
0
2
0.00
2.24
0.95
0.16
220375
0
2
0.00
2.24
0.95
0.16
260375
0
2
0.00
2.24
0.95
0.16
100376
0
2
0.00
2.24
0.95
0.16
140376
0
2
0.00
2.24
0.95
0.16
180376
0
2
0.00
2.24
0.95
0.16
220376
0
2
0.00
2.24
0.95
0.16
260376
0
2
0.00
2.24
0.95
0.16
100377
0
2
0.00
2.24
0.95
0.16
140377
0
2
0.00
2.24
0.95
0.16
180377
0
2
0.00
2.24
0.95
0.16
220377
0
2
0.00
2.24
0.95
0.16
260377
0
2
0.00
2.24
0.95
0.16
100378
0
2
0.00
2.24
0.95
0.16
140378
0
2
0.00
2.24
0.95
0.16
180378
0
2
0.00
2.24
0.95
0.16
220378
0
2
0.00
2.24
0.95
0.16
260378
0
2
0.00
2.24
0.95
0.16
100379
0
2
0.00
2.24
0.95
0.16
140379
0
2
0.00
2.24
0.95
0.16
180379
0
2
0.00
2.24
0.95
0.16
220379
0
2
0.00
2.24
0.95
0.16
260379
0
2
0.00
2.24
0.95
0.16
100380
0
2
0.00
2.24
0.95
0.16
140380
0
2
0.00
2.24
0.95
0.16
180380
0
2
0.00
2.24
0.95
0.16
220380
0
2
0.00
2.24
0.95
0.16
260380
0
2
0.00
2.24
0.95
0.16
100381
0
2
0.00
2.24
0.95
0.16
140381
0
2
0.00
2.24
0.95
0.16
180381
0
2
0.00
2.24
0.95
0.16
220381
0
2
0.00
2.24
0.95
0.16
260381
0
2
0.00
2.24
0.95
0.16
100382
0
2
0.00
2.24
0.95
0.16
140382
0
2
0.00
2.24
0.95
0.16
180382
0
2
0.00
2.24
0.95
0.16
220382
0
2
0.00
2.24
0.95
0.16
260382
0
2
0.00
2.24
0.95
0.16
100383
0
2
0.00
2.24
0.95
0.16
140383
0
2
0.00
2.24
0.95
0.16
109
180383
0
2
0.00
2.24
0.95
0.16
220383
0
2
0.00
2.24
0.95
0.16
260383
0
2
0.00
2.24
0.95
0.16
***
Record
17:
Filtra.,
disposit.
foliar
pest.
after
harvest,
and
plant
uptake
***
0.0
3
0.0
***
Record
18:
Foliar
dissipation
parameters
***
0.0
0.0
0.50
Cornelius
silt
loam,
15%
slope,
Hydrologic
Group:
C
148.0
0
0
0
0
0
0
0
0
0
***
Record
26:
Soil
volatilization
constants
***
0.0
0.0
0.0
***
Record
33
***
5
***
Record
34
***
1
15.0
1.30
0.329
0.0
0.0
0.0
***
Record
36:
Soil
half
life
rate
constants;
repeat
for
each
horizon
***
0.058
0.058
0.0
***
Record
37:
***
0.1
0.329
0.099
2.30
3.0
***
Record
39:
Omitted;
parent/
daughter
transformation
rates
***
2
13.0
1.38
0.338
0.0
0.0
0.0
0.029
0.029
0.0
1.0
0.338
0.108
1.11
3.0
3
15.0
1.58
0.340
0.0
0.0
0.0
0.029
0.029
0.0
1.0
0.340
0.110
0.21
3.0
4
55.0
1.52
0.358
0.0
0.0
0.0
0.029
0.029
0.0
5.0
0.358
0.148
0.145
3.0
5
50.0
1.46
0.202
0.0
0.0
0.0
0.029
0.029
0.0
5.0
0.202
0.142
0.07
3.0
0
YEAR
5
YEAR
5
YEAR
5
1
1
1
6
YEAR
PRCP
TSER
0
0
RUNF
TSER
0
0
ESLS
TSER
0
0
1.0E3
RFLX
TSER
0
0
1.0E5
EFLX
TSER
0
0
1.0E5
RZFX
TSER
0
0
1.0E5
110
Average
Application
Rate:
Oregon
Apples,
Index
Reservoir
***
PRZM
3.1
Input
Data
File;
ORAPPLEX.
INP;
Modified
April
5,
1998
***
***
Modified
for
Carbaryl
by
Laurence
Libelo,
6/
21/
00
***
***
Use
rate
changed
to
QUA
(July
21,
1998
QUA
Report)
AVERAGE
VALUES
on
2/
28/
01
***
***
Crops
simulated:
Apples,
Crabapples,
and
Quince
***
***
Location
Washington
County,
Oregon;
Meadow/
Orchard
Scenario;
MLRA:
A2
***
***
Manning's
N:
Assume
sparse
grass
under
mature
trees
(ca.
20
feet)
***
***
Temperature
data
read
***
***
This
file
is
for
scenario
standardization;
Reference
chemical
is
Atrazine
***
***
See
ORAPPLEX.
wpd
for
scenario
details
***
Carbaryl
Cornelius
silt
loam,
15%
slope,
Hydrologic
Group:
C
0.740
0.150
2
17.000
1
3
9.2
10.3
11.8
13.6
15.30
15.3
14.2
12.5
10.9
9.4
8.6
9.1
4
0.43
3.30
1.0
10.0
5.4
2
15.00
354.0
1
1
0.25
17.0
100.000
3
91
71
71
0.0
600
1
3
0103
0105
0112
0.01
0.01
0.01
0.015
0.015
0.015
36
010448
150548
151248
1
010449
150549
151249
1
010450
150550
151250
1
010451
150551
151251
1
010452
150552
151252
1
010453
150553
151253
1
010454
150554
151254
1
010455
150555
151255
1
010456
150556
151256
1
010457
150557
151257
1
010458
150558
151258
1
010459
150559
151259
1
010460
150560
151260
1
010461
150561
151261
1
010462
150562
151262
1
010463
150563
151263
1
010464
150564
151264
1
010465
150565
151265
1
010466
150566
151266
1
111
010467
150567
151267
1
010468
150568
151268
1
010469
150569
151269
1
010470
150570
151270
1
010471
150571
151271
1
010472
150572
151272
1
010473
150573
151273
1
010474
150574
151274
1
010475
150575
151275
1
010476
150576
151276
1
010477
150577
151277
1
010478
150578
151278
1
010479
150579
151279
1
010480
150580
151280
1
010481
150581
151281
1
010482
150582
151282
1
010483
150583
151283
1
Use
rate
changed
to
QUA
(July
21,
1998
QUA
Report)
AVERAGE
VALUES
on
2/
28/
01
2
apps@
1.2
lb/
app
***
***
Aerial
Application:
5
apps
of
2
lb
a.
i./
acre
(3.3
kg/
ha),
Aerial
@
95%
eff.
w/
16%
drift
72
1
0
0
Chemical
Kd:
3.0
(silt
Loam
soil);
AeSM:
T1/
2:
12
days;
AnSM:
T1/
2
=
24
days
***
Record
16:
Application
information;
set
specific
to
carbaryl
***
300448
0
2
0.00
1.34
0.95
0.16
140548
0
2
0.00
1.34
0.95
0.16
300449
0
2
0.00
1.34
0.95
0.16
140549
0
2
0.00
1.34
0.95
0.16
300450
0
2
0.00
1.34
0.95
0.16
140550
0
2
0.00
1.34
0.95
0.16
300451
0
2
0.00
1.34
0.95
0.16
140551
0
2
0.00
1.34
0.95
0.16
300452
0
2
0.00
1.34
0.95
0.16
140552
0
2
0.00
1.34
0.95
0.16
300453
0
2
0.00
1.34
0.95
0.16
140553
0
2
0.00
1.34
0.95
0.16
300454
0
2
0.00
1.34
0.95
0.16
140554
0
2
0.00
1.34
0.95
0.16
300455
0
2
0.00
1.34
0.95
0.16
140555
0
2
0.00
1.34
0.95
0.16
300456
0
2
0.00
1.34
0.95
0.16
140556
0
2
0.00
1.34
0.95
0.16
300457
0
2
0.00
1.34
0.95
0.16
140557
0
2
0.00
1.34
0.95
0.16
300458
0
2
0.00
1.34
0.95
0.16
140558
0
2
0.00
1.34
0.95
0.16
300459
0
2
0.00
1.34
0.95
0.16
140559
0
2
0.00
1.34
0.95
0.16
112
300460
0
2
0.00
1.34
0.95
0.16
140560
0
2
0.00
1.34
0.95
0.16
300461
0
2
0.00
1.34
0.95
0.16
140561
0
2
0.00
1.34
0.95
0.16
300462
0
2
0.00
1.34
0.95
0.16
140562
0
2
0.00
1.34
0.95
0.16
300463
0
2
0.00
1.34
0.95
0.16
140563
0
2
0.00
1.34
0.95
0.16
300464
0
2
0.00
1.34
0.95
0.16
140564
0
2
0.00
1.34
0.95
0.16
300465
0
2
0.00
1.34
0.95
0.16
140565
0
2
0.00
1.34
0.95
0.16
300466
0
2
0.00
1.34
0.95
0.16
140566
0
2
0.00
1.34
0.95
0.16
300467
0
2
0.00
1.34
0.95
0.16
140567
0
2
0.00
1.34
0.95
0.16
300468
0
2
0.00
1.34
0.95
0.16
140568
0
2
0.00
1.34
0.95
0.16
300469
0
2
0.00
1.34
0.95
0.16
140569
0
2
0.00
1.34
0.95
0.16
300470
0
2
0.00
1.34
0.95
0.16
140570
0
2
0.00
1.34
0.95
0.16
300471
0
2
0.00
1.34
0.95
0.16
140571
0
2
0.00
1.34
0.95
0.16
300472
0
2
0.00
1.34
0.95
0.16
140572
0
2
0.00
1.34
0.95
0.16
300473
0
2
0.00
1.34
0.95
0.16
140573
0
2
0.00
1.34
0.95
0.16
300474
0
2
0.00
1.34
0.95
0.16
140574
0
2
0.00
1.34
0.95
0.16
300475
0
2
0.00
1.34
0.95
0.16
140575
0
2
0.00
1.34
0.95
0.16
300476
0
2
0.00
1.34
0.95
0.16
140576
0
2
0.00
1.34
0.95
0.16
300477
0
2
0.00
1.34
0.95
0.16
140577
0
2
0.00
1.34
0.95
0.16
300478
0
2
0.00
1.34
0.95
0.16
140578
0
2
0.00
1.34
0.95
0.16
300479
0
2
0.00
1.34
0.95
0.16
140579
0
2
0.00
1.34
0.95
0.16
300480
0
2
0.00
1.34
0.95
0.16
140580
0
2
0.00
1.34
0.95
0.16
300481
0
2
0.00
1.34
0.95
0.16
140581
0
2
0.00
1.34
0.95
0.16
300482
0
2
0.00
1.34
0.95
0.16
140582
0
2
0.00
1.34
0.95
0.16
300483
0
2
0.00
1.34
0.95
0.16
140583
0
2
0.00
1.34
0.95
0.16
113
***
Record
17:
Filtra.,
disposit.
foliar
pest.
after
harvest,
and
plant
uptake
***
0.0
3
0.0
***
Record
18:
Foliar
dissipation
parameters
***
0.0
0.0
0.50
Cornelius
silt
loam,
15%
slope,
Hydrologic
Group:
C
148.0
0
0
0
0
0
0
0
0
0
***
Record
26:
Soil
volatilization
constants
***
0.0
0.0
0.0
***
Record
33
***
5
***
Record
34
***
1
15.0
1.30
0.329
0.0
0.0
0.0
***
Record
36:
Soil
half
life
rate
constants;
repeat
for
each
horizon
***
0.058
0.058
0.0
***
Record
37:
***
0.1
0.329
0.099
2.30
3.0
***
Record
39:
Omitted;
parent/
daughter
transformation
rates
***
2
13.0
1.38
0.338
0.0
0.0
0.0
0.029
0.029
0.0
1.0
0.338
0.108
1.11
3.0
3
15.0
1.58
0.340
0.0
0.0
0.0
0.029
0.029
0.0
1.0
0.340
0.110
0.21
3.0
4
55.0
1.52
0.358
0.0
0.0
0.0
0.029
0.029
0.0
5.0
0.358
0.148
0.145
3.0
5
50.0
1.46
0.202
0.0
0.0
0.0
0.029
0.029
0.0
5.0
0.202
0.142
0.07
3.0
0
YEAR
5
YEAR
5
YEAR
5
1
1
1
6
YEAR
PRCP
TSER
0
0
RUNF
TSER
0
0
ESLS
TSER
0
0
1.0E3
RFLX
TSER
0
0
1.0E5
EFLX
TSER
0
0
1.0E5
RZFX
TSER
0
0
1.0E5
114
Maximum
Reported
Application
Rate:
Oregon
Apples,
Index
Reservoir
***
PRZM
3.1
Input
Data
File;
ORAPPLEX.
INP;
Modified
April
5,
1998
***
***
Modified
for
Carbaryl
by
Laurence
Libelo,
6/
21/
00
***
Modified
for
Index
Res.
by
Laurence
Libelo,
3/
7/
01
***
Crops
simulated:
Apples,
Crabapples,
and
Quince
***
***
Location
Washington
County,
Oregon;
Meadow/
Orchard
Scenario;
MLRA:
A2
***
***
Manning's
N:
Assume
sparse
grass
under
mature
trees
(ca.
20
feet)
***
***
Temperature
data
read
***
***
This
file
is
for
scenario
standardization;
Reference
chemical
is
Atrazine
***
***
See
ORAPPLEX.
wpd
for
scenario
details
***
Carbaryl
Cornelius
silt
loam,
15%
slope,
Hydrologic
Group:
C
0.740
0.150
2
17.000
1
3
9.2
10.3
11.8
13.6
15.30
15.3
14.2
12.5
10.9
9.4
8.6
9.1
4
0.43
3.30
1.0
172.8
5.4
2
15.00
464
1
1
0.25
17.0
100.000
3
91
71
71
0.0
600
1
3
0103
0105
0112
0.01
0.01
0.01
0.015
0.015
0.015
36
010448
150548
151248
1
010449
150549
151249
1
010450
150550
151250
1
010451
150551
151251
1
010452
150552
151252
1
010453
150553
151253
1
010454
150554
151254
1
010455
150555
151255
1
010456
150556
151256
1
010457
150557
151257
1
010458
150558
151258
1
010459
150559
151259
1
010460
150560
151260
1
010461
150561
151261
1
010462
150562
151262
1
010463
150563
151263
1
010464
150564
151264
1
010465
150565
151265
1
010466
150566
151266
1
010467
150567
151267
1
115
010468
150568
151268
1
010469
150569
151269
1
010470
150570
151270
1
010471
150571
151271
1
010472
150572
151272
1
010473
150573
151273
1
010474
150574
151274
1
010475
150575
151275
1
010476
150576
151276
1
010477
150577
151277
1
010478
150578
151278
1
010479
150579
151279
1
010480
150580
151280
1
010481
150581
151281
1
010482
150582
151282
1
010483
150583
151283
1
Max
reported
rate
2
apps
@
1.6
lb
A.
I./
acre
***
Aerial
Application:
5
apps
of
2
lb
a.
i./
acre
(2.2
kg/
ha),
Aerial
@
95%
eff.
w/
16%
drift
72
1
0
0
Chemical
Kd:
3.0
(silt
Loam
soil);
AeSM:
T1/
2:
12
days;
AnSM:
T1/
2
=
24
days
***
Record
16:
Application
information;
set
specific
to
carbaryl
***
300448
0
2
0.00
1.79
0.95
0.16
140548
0
2
0.00
1.79
0.95
0.16
300449
0
2
0.00
1.79
0.95
0.16
140549
0
2
0.00
1.79
0.95
0.16
300450
0
2
0.00
1.79
0.95
0.16
140550
0
2
0.00
1.79
0.95
0.16
300451
0
2
0.00
1.79
0.95
0.16
140551
0
2
0.00
1.79
0.95
0.16
300452
0
2
0.00
1.79
0.95
0.16
140552
0
2
0.00
1.79
0.95
0.16
300453
0
2
0.00
1.79
0.95
0.16
140553
0
2
0.00
1.79
0.95
0.16
300454
0
2
0.00
1.79
0.95
0.16
140554
0
2
0.00
1.79
0.95
0.16
300455
0
2
0.00
1.79
0.95
0.16
140555
0
2
0.00
1.79
0.95
0.16
300456
0
2
0.00
1.79
0.95
0.16
140556
0
2
0.00
1.79
0.95
0.16
300457
0
2
0.00
1.79
0.95
0.16
140557
0
2
0.00
1.79
0.95
0.16
300458
0
2
0.00
1.79
0.95
0.16
140558
0
2
0.00
1.79
0.95
0.16
300459
0
2
0.00
1.79
0.95
0.16
140559
0
2
0.00
1.79
0.95
0.16
300460
0
2
0.00
1.79
0.95
0.16
140560
0
2
0.00
1.79
0.95
0.16
116
300461
0
2
0.00
1.79
0.95
0.16
140561
0
2
0.00
1.79
0.95
0.16
300462
0
2
0.00
1.79
0.95
0.16
140562
0
2
0.00
1.79
0.95
0.16
300463
0
2
0.00
1.79
0.95
0.16
140563
0
2
0.00
1.79
0.95
0.16
300464
0
2
0.00
1.79
0.95
0.16
140564
0
2
0.00
1.79
0.95
0.16
300465
0
2
0.00
1.79
0.95
0.16
140565
0
2
0.00
1.79
0.95
0.16
300466
0
2
0.00
1.79
0.95
0.16
140566
0
2
0.00
1.79
0.95
0.16
300467
0
2
0.00
1.79
0.95
0.16
140567
0
2
0.00
1.79
0.95
0.16
300468
0
2
0.00
1.79
0.95
0.16
140568
0
2
0.00
1.79
0.95
0.16
300469
0
2
0.00
1.79
0.95
0.16
140569
0
2
0.00
1.79
0.95
0.16
300470
0
2
0.00
1.79
0.95
0.16
140570
0
2
0.00
1.79
0.95
0.16
300471
0
2
0.00
1.79
0.95
0.16
140571
0
2
0.00
1.79
0.95
0.16
300472
0
2
0.00
1.79
0.95
0.16
140572
0
2
0.00
1.79
0.95
0.16
300473
0
2
0.00
1.79
0.95
0.16
140573
0
2
0.00
1.79
0.95
0.16
300474
0
2
0.00
1.79
0.95
0.16
140574
0
2
0.00
1.79
0.95
0.16
300475
0
2
0.00
1.79
0.95
0.16
140575
0
2
0.00
1.79
0.95
0.16
300476
0
2
0.00
1.79
0.95
0.16
140576
0
2
0.00
1.79
0.95
0.16
300477
0
2
0.00
1.79
0.95
0.16
140577
0
2
0.00
1.79
0.95
0.16
300478
0
2
0.00
1.79
0.95
0.16
140578
0
2
0.00
1.79
0.95
0.16
300479
0
2
0.00
1.79
0.95
0.16
140579
0
2
0.00
1.79
0.95
0.16
300480
0
2
0.00
1.79
0.95
0.16
140580
0
2
0.00
1.79
0.95
0.16
300481
0
2
0.00
1.79
0.95
0.16
140581
0
2
0.00
1.79
0.95
0.16
300482
0
2
0.00
1.79
0.95
0.16
140582
0
2
0.00
1.79
0.95
0.16
300483
0
2
0.00
1.79
0.95
0.16
140583
0
2
0.00
1.79
0.95
0.16
***
Record
17:
Filtra.,
disposit.
foliar
pest.
after
harvest,
and
plant
uptake
***
0.0
3
0.0
117
***
Record
18:
Foliar
dissipation
parameters
***
0.0
0.0
0.50
Cornelius
silt
loam,
15%
slope,
Hydrologic
Group:
C
148.0
0
0
0
0
0
0
0
0
0
***
Record
26:
Soil
volatilization
constants
***
0.0
0.0
0.0
***
Record
33
***
5
***
Record
34
***
1
15.0
1.30
0.329
0.0
0.0
0.0
***
Record
36:
Soil
half
life
rate
constants;
repeat
for
each
horizon
***
0.058
0.058
0.0
***
Record
37:
***
0.1
0.329
0.099
2.30
3.0
***
Record
39:
Omitted;
parent/
daughter
transformation
rates
***
2
13.0
1.38
0.338
0.0
0.0
0.0
0.029
0.029
0.0
1.0
0.338
0.108
1.11
3.0
3
15.0
1.58
0.340
0.0
0.0
0.0
0.029
0.029
0.0
1.0
0.340
0.110
0.21
3.0
4
55.0
1.52
0.358
0.0
0.0
0.0
0.029
0.029
0.0
5.0
0.358
0.148
0.145
3.0
5
50.0
1.46
0.202
0.0
0.0
0.0
0.029
0.029
0.0
5.0
0.202
0.142
0.07
3.0
0
YEAR
5
YEAR
5
YEAR
5
1
1
1
6
YEAR
PRCP
TSER
0
0
RUNF
TSER
0
0
ESLS
TSER
0
0
1.0E3
RFLX
TSER
0
0
1.0E5
EFLX
TSER
0
0
1.0E5
RZFX
TSER
0
0
1.0E5
118
Maximum
Application
Rate:
Sugar
beets,
Index
Reservoir
***
PRZM2
Version
3.12
Input
Data
File
***
***
MNSUGAR1.
inp
Index
Reservoir
Scenario
created
on
12/
13/
99
***
***
Modified
for
CABRBARYL
6/
21/
00
by
Laurence
Libelo
***
***
Bearden
soil
is
a
Benchmark
soil
with
ca.
800K
mapped
acres
in
MLRA
***
***
Sugar
beets,
conventional
tillage
***
***
Highest
acreage
sugarbeet
state
is
MN;
highest
county
in
MN
is
Polk
***
***
Manning's
N
value
set
to
0.02
for
residues
applied
to
fallow
surfaces
***
***
Application
timing
information
provided
by
Russ
Severson
(?),
***
University
of
Minnesota
Agricultural
Extension
Service,
Polk
County,
MN,
***
(218)
281
8696
***
PCA
for
sugarbeets
not
available,
use
default
PCA
of
0.87
***
Chemical:
Carbaryl
Bearden
Silty
Clay
Loam;
HYGP:
C;
MLRA
F
56,
Polk
County,
Minnesota
0.760
0.500
0
12.00
1
3
4
0.28
0.12
0.50
172.80
3
3.00
600.0
1
1
0.10
20.00
80.00
3
91
82
91
0.00
100.00
1
3
0101
1605
1110
0.43
0.18
0.43
0.02
0.02
0.02
36
160548
061048
161048
1
160549
061049
161049
1
160550
061050
161050
1
160551
061051
161051
1
160552
061052
161052
1
160553
061053
161053
1
160554
061054
161054
1
160555
061055
161055
1
160556
061056
161056
1
160557
061057
161057
1
160558
061058
161058
1
160559
061059
161059
1
160560
061060
161060
1
160561
061061
161061
1
160562
061062
161062
1
160563
061063
161063
1
160564
061064
161064
1
160565
061065
161065
1
119
160566
061066
161066
1
160567
061067
161067
1
160568
061068
161068
1
160569
061069
161069
1
160570
061070
161070
1
160571
061071
161071
1
160572
061072
161072
1
160573
061073
161073
1
160574
061074
161074
1
160575
061075
161075
1
160576
061076
161076
1
160577
061077
161077
1
160578
061078
161078
1
160579
061079
161079
1
160580
061080
161080
1
160581
061081
161081
1
160582
061082
161082
1
160583
061083
161083
1
Application
Schedule:
2
aerial
app
@
1.5
lb
a.
i./
acre
(1.68
kg/
ha,
95%
app.
eff,
16%
spray
drift
72
1
0
0
Carbaryl:
Kd:
3.0;
AeSM:
T1/
2
=
12
days;
AnSM:
T1/
2
=
24
days
300448
0
2
0.00
1.68
0.95
0.16
140548
0
2
0.00
1.68
0.95
0.16
300449
0
2
0.00
1.68
0.95
0.16
140549
0
2
0.00
1.68
0.95
0.16
300450
0
2
0.00
1.68
0.95
0.16
140550
0
2
0.00
1.68
0.95
0.16
300451
0
2
0.00
1.68
0.95
0.16
140551
0
2
0.00
1.68
0.95
0.16
300452
0
2
0.00
1.68
0.95
0.16
140552
0
2
0.00
1.68
0.95
0.16
300453
0
2
0.00
1.68
0.95
0.16
140553
0
2
0.00
1.68
0.95
0.16
300454
0
2
0.00
1.68
0.95
0.16
140554
0
2
0.00
1.68
0.95
0.16
300455
0
2
0.00
1.68
0.95
0.16
140555
0
2
0.00
1.68
0.95
0.16
300456
0
2
0.00
1.68
0.95
0.16
140556
0
2
0.00
1.68
0.95
0.16
300457
0
2
0.00
1.68
0.95
0.16
140557
0
2
0.00
1.68
0.95
0.16
300458
0
2
0.00
1.68
0.95
0.16
140558
0
2
0.00
1.68
0.95
0.16
300459
0
2
0.00
1.68
0.95
0.16
140559
0
2
0.00
1.68
0.95
0.16
300460
0
2
0.00
1.68
0.95
0.16
140560
0
2
0.00
1.68
0.95
0.16
300461
0
2
0.00
1.68
0.95
0.16
140561
0
2
0.00
1.68
0.95
0.16
120
300462
0
2
0.00
1.68
0.95
0.16
140562
0
2
0.00
1.68
0.95
0.16
300463
0
2
0.00
1.68
0.95
0.16
140563
0
2
0.00
1.68
0.95
0.16
300464
0
2
0.00
1.68
0.95
0.16
140564
0
2
0.00
1.68
0.95
0.16
300465
0
2
0.00
1.68
0.95
0.16
140565
0
2
0.00
1.68
0.95
0.16
300466
0
2
0.00
1.68
0.95
0.16
140566
0
2
0.00
1.68
0.95
0.16
300467
0
2
0.00
1.68
0.95
0.16
140567
0
2
0.00
1.68
0.95
0.16
300468
0
2
0.00
1.68
0.95
0.16
140568
0
2
0.00
1.68
0.95
0.16
300469
0
2
0.00
1.68
0.95
0.16
140569
0
2
0.00
1.68
0.95
0.16
300470
0
2
0.00
1.68
0.95
0.16
140570
0
2
0.00
1.68
0.95
0.16
300471
0
2
0.00
1.68
0.95
0.16
140571
0
2
0.00
1.68
0.95
0.16
300472
0
2
0.00
1.68
0.95
0.16
140572
0
2
0.00
1.68
0.95
0.16
300473
0
2
0.00
1.68
0.95
0.16
140573
0
2
0.00
1.68
0.95
0.16
300474
0
2
0.00
1.68
0.95
0.16
140574
0
2
0.00
1.68
0.95
0.16
300475
0
2
0.00
1.68
0.95
0.16
140575
0
2
0.00
1.68
0.95
0.16
300476
0
2
0.00
1.68
0.95
0.16
140576
0
2
0.00
1.68
0.95
0.16
300477
0
2
0.00
1.68
0.95
0.16
140577
0
2
0.00
1.68
0.95
0.16
300478
0
2
0.00
1.68
0.95
0.16
140578
0
2
0.00
1.68
0.95
0.16
300479
0
2
0.00
1.68
0.95
0.16
140579
0
2
0.00
1.68
0.95
0.16
300480
0
2
0.00
1.68
0.95
0.16
140580
0
2
0.00
1.68
0.95
0.16
300481
0
2
0.00
1.68
0.95
0.16
140581
0
2
0.00
1.68
0.95
0.16
300482
0
2
0.00
1.68
0.95
0.16
140582
0
2
0.00
1.68
0.95
0.16
300483
0
2
0.00
1.68
0.95
0.16
140583
0
2
0.00
1.68
0.95
0.16
0.0
3
0.00
0.0
0.00
0.50
Bearden
Silty
Clay
Loam;
Hydrologic
Group
C;
100.00
0
0
0
0
0
0
0
0
0
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
121
4
1
10.00
1.400
0.377
0.000
0.000
0.58
0.58
0.00
0.10
0.377
0.207
1.160
3.0
2
8.00
1.400
0.377
0.000
0.000
0.029
0.029
0.00
1.00
0.377
0.207
1.160
3.0
3
54.00
1.500
0.292
0.000
0.000
0.029
0.029
0.00
2.00
0.292
0.132
1.160
3.0
4
28.00
1.800
0.285
0.000
0.000
0.029
0.029
0.00
2.0
0.285
0.125
0.174
3.0
0
YEAR
5
YEAR
5
YEAR
5
1
1
1
1
YEAR
***
PRCP
TSER
0
0***
RUNF
TCUM
0
0
***
ESLS
TSER
0
0
1.0E3***
***
RFLX
TSER
0
0
1.0E5***
***
EFLX
TSER
0
0
1.0E5***
***
RZFX
TSER
0
0
1.0E5***
122
Average
Application
Rate:
Sugar
beets,
Index
Reservoir
***
PRZM2
Version
3.12
Input
Data
File
***
***
MNSUGAR1.
inp
Index
Reservoir
Scenario
created
on
12/
13/
99
***
***
Modified
for
CABRBARYL
6/
21/
00
by
Laurence
Libelo
***
***
Use
rate
changed
to
QUA
(July
21,
1998
QUA
Report)
AVERAGE
VALUES
on
2/
28/
01
***
***
Bearden
soil
is
a
Benchmark
soil
with
ca.
800K
mapped
acres
in
MLRA
***
***
Sugar
beets,
conventional
tillage
***
***
Highest
acreage
sugarbeet
state
is
MN;
highest
county
in
MN
is
Polk
***
***
Manning's
N
value
set
to
0.02
for
residues
applied
to
fallow
surfaces
***
***
Application
timing
information
provided
by
Russ
Severson
(?),
***
University
of
Minnesota
Agricultural
Extension
Service,
Polk
County,
MN,
***
(218)
281
8696
***
PCA
for
sugarbeets
not
available,
use
default
PCA
of
0.87
***
Chemical:
Carbaryl
Bearden
Silty
Clay
Loam;
HYGP:
C;
MLRA
F
56,
Polk
County,
Minnesota
0.760
0.500
0
12.00
1
3
4
0.28
0.12
0.50
172.80
3
3.00
600.0
1
1
0.10
20.00
80.00
3
91
82
91
0.00
100.00
1
3
0101
1605
1110
0.43
0.18
0.43
0.02
0.02
0.02
36
160548
061048
161048
1
160549
061049
161049
1
160550
061050
161050
1
160551
061051
161051
1
160552
061052
161052
1
160553
061053
161053
1
160554
061054
161054
1
160555
061055
161055
1
160556
061056
161056
1
160557
061057
161057
1
160558
061058
161058
1
160559
061059
161059
1
160560
061060
161060
1
160561
061061
161061
1
160562
061062
161062
1
160563
061063
161063
1
160564
061064
161064
1
123
160565
061065
161065
1
160566
061066
161066
1
160567
061067
161067
1
160568
061068
161068
1
160569
061069
161069
1
160570
061070
161070
1
160571
061071
161071
1
160572
061072
161072
1
160573
061073
161073
1
160574
061074
161074
1
160575
061075
161075
1
160576
061076
161076
1
160577
061077
161077
1
160578
061078
161078
1
160579
061079
161079
1
160580
061080
161080
1
160581
061081
161081
1
160582
061082
161082
1
160583
061083
161083
1
Application
Schedule:
1
aerial
app
@
1.5
lb
a.
i./
acre
(1.68
kg/
ha,
95%
app.
eff,
5%
spray
drift
***
***
Application
Schedule:
2
aerial
app
@
1.5
lb
a.
i./
acre
(1.68
kg/
ha,
95%
app.
eff,
16%
spray
drift
36
1
0
0
Carbaryl:
Kd:
3.0;
AeSM:
T1/
2
=
12
days;
AnSM:
T1/
2
=
24
days
300448
0
2
0.00
1.68
0.95
0.16
300449
0
2
0.00
1.68
0.95
0.16
300450
0
2
0.00
1.68
0.95
0.16
300451
0
2
0.00
1.68
0.95
0.16
300452
0
2
0.00
1.68
0.95
0.16
300453
0
2
0.00
1.68
0.95
0.16
300454
0
2
0.00
1.68
0.95
0.16
300455
0
2
0.00
1.68
0.95
0.16
300456
0
2
0.00
1.68
0.95
0.16
300457
0
2
0.00
1.68
0.95
0.16
300458
0
2
0.00
1.68
0.95
0.16
300459
0
2
0.00
1.68
0.95
0.16
300460
0
2
0.00
1.68
0.95
0.16
300461
0
2
0.00
1.68
0.95
0.16
300462
0
2
0.00
1.68
0.95
0.16
300463
0
2
0.00
1.68
0.95
0.16
300464
0
2
0.00
1.68
0.95
0.16
300465
0
2
0.00
1.68
0.95
0.16
300466
0
2
0.00
1.68
0.95
0.16
300467
0
2
0.00
1.68
0.95
0.16
300468
0
2
0.00
1.68
0.95
0.16
300469
0
2
0.00
1.68
0.95
0.16
300470
0
2
0.00
1.68
0.95
0.16
300471
0
2
0.00
1.68
0.95
0.16
300472
0
2
0.00
1.68
0.95
0.16
124
300473
0
2
0.00
1.68
0.95
0.16
300474
0
2
0.00
1.68
0.95
0.16
300475
0
2
0.00
1.68
0.95
0.16
300476
0
2
0.00
1.68
0.95
0.16
300477
0
2
0.00
1.68
0.95
0.16
300478
0
2
0.00
1.68
0.95
0.16
300479
0
2
0.00
1.68
0.95
0.16
300480
0
2
0.00
1.68
0.95
0.16
300481
0
2
0.00
1.68
0.95
0.16
300482
0
2
0.00
1.68
0.95
0.16
300483
0
2
0.00
1.68
0.95
0.16
0.0
3
0.00
0.0
0.00
0.50
Bearden
Silty
Clay
Loam;
Hydrologic
Group
C;
100.00
0
0
0
0
0
0
0
0
0
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
4
1
10.00
1.400
0.377
0.000
0.000
0.58
0.58
0.00
0.10
0.377
0.207
1.160
3.0
2
8.00
1.400
0.377
0.000
0.000
0.029
0.029
0.00
1.00
0.377
0.207
1.160
3.0
3
54.00
1.500
0.292
0.000
0.000
0.029
0.029
0.00
2.00
0.292
0.132
1.160
3.0
4
28.00
1.800
0.285
0.000
0.000
0.029
0.029
0.00
2.0
0.285
0.125
0.174
3.0
0
YEAR
5
YEAR
5
YEAR
5
1
1
1
1
YEAR
***
PRCP
TSER
0
0***
RUNF
TCUM
0
0
***
ESLS
TSER
0
0
1.0E3***
***
RFLX
TSER
0
0
1.0E5***
***
EFLX
TSER
0
0
1.0E5***
***
RZFX
TSER
0
0
1.0E5***
125
Maximum
Reported
Application
Rate:
Sugar
beets,
Index
Reservoir
***
PRZM2
Version
3.12
Input
Data
File
***
***
MNSUGAR1.
inp
Index
Reservoir
Scenario
created
on
12/
13/
99
***
***
Modified
for
CABRBARYL
6/
21/
00
by
Laurence
Libelo
***
***
Use
rate
changed
to
QUA
(July
21,
1998
QUA
Report)
AVERAGE
VALUES
on
2/
28/
01
***
***
Bearden
soil
is
a
Benchmark
soil
with
ca.
800K
mapped
acres
in
MLRA
***
***
Sugar
beets,
conventional
tillage
***
***
Highest
acreage
sugarbeet
state
is
MN;
highest
county
in
MN
is
Polk
***
***
Manning's
N
value
set
to
0.02
for
residues
applied
to
fallow
surfaces
***
***
Application
timing
information
provided
by
Russ
Severson
(?),
***
University
of
Minnesota
Agricultural
Extension
Service,
Polk
County,
MN,
***
(218)
281
8696
***
PCA
for
sugarbeets
not
available,
use
default
PCA
of
0.87
***
Chemical:
Carbaryl
Bearden
Silty
Clay
Loam;
HYGP:
C;
MLRA
F
56,
Polk
County,
Minnesota
0.760
0.500
0
12.00
1
3
4
0.28
0.12
0.50
172.80
3
3.00
600.0
1
1
0.10
20.00
80.00
3
91
82
91
0.00
100.00
1
3
0101
1605
1110
0.43
0.18
0.43
0.02
0.02
0.02
36
160548
061048
161048
1
160549
061049
161049
1
160550
061050
161050
1
160551
061051
161051
1
160552
061052
161052
1
160553
061053
161053
1
160554
061054
161054
1
160555
061055
161055
1
160556
061056
161056
1
160557
061057
161057
1
160558
061058
161058
1
160559
061059
161059
1
160560
061060
161060
1
160561
061061
161061
1
160562
061062
161062
1
160563
061063
161063
1
160564
061064
161064
1
160565
061065
161065
1
126
160566
061066
161066
1
160567
061067
161067
1
160568
061068
161068
1
160569
061069
161069
1
160570
061070
161070
1
160571
061071
161071
1
160572
061072
161072
1
160573
061073
161073
1
160574
061074
161074
1
160575
061075
161075
1
160576
061076
161076
1
160577
061077
161077
1
160578
061078
161078
1
160579
061079
161079
1
160580
061080
161080
1
160581
061081
161081
1
160582
061082
161082
1
160583
061083
161083
1
Maximum
raported
application
rate:
1
app
@
1.2
lb
A.
I./
acre
***
Application
Schedule:
2
aerial
app
@
1.5
lb
a.
i./
acre
(1.68
kg/
ha,
95%
app.
eff,
16%
spray
drift
36
1
0
0
Carbaryl:
Kd:
3.0;
AeSM:
T1/
2
=
12
days;
AnSM:
T1/
2
=
24
days
300448
0
2
0.00
1.34
0.95
0.16
300449
0
2
0.00
1.34
0.95
0.16
300450
0
2
0.00
1.34
0.95
0.16
300451
0
2
0.00
1.34
0.95
0.16
300452
0
2
0.00
1.34
0.95
0.16
300453
0
2
0.00
1.34
0.95
0.16
300454
0
2
0.00
1.34
0.95
0.16
300455
0
2
0.00
1.34
0.95
0.16
300456
0
2
0.00
1.34
0.95
0.16
300457
0
2
0.00
1.34
0.95
0.16
300458
0
2
0.00
1.34
0.95
0.16
300459
0
2
0.00
1.34
0.95
0.16
300460
0
2
0.00
1.34
0.95
0.16
300461
0
2
0.00
1.34
0.95
0.16
300462
0
2
0.00
1.34
0.95
0.16
300463
0
2
0.00
1.34
0.95
0.16
300464
0
2
0.00
1.34
0.95
0.16
300465
0
2
0.00
1.34
0.95
0.16
300466
0
2
0.00
1.34
0.95
0.16
300467
0
2
0.00
1.34
0.95
0.16
300468
0
2
0.00
1.34
0.95
0.16
300469
0
2
0.00
1.34
0.95
0.16
300470
0
2
0.00
1.34
0.95
0.16
300471
0
2
0.00
1.34
0.95
0.16
300472
0
2
0.00
1.34
0.95
0.16
300473
0
2
0.00
1.34
0.95
0.16
300474
0
2
0.00
1.34
0.95
0.16
300475
0
2
0.00
1.34
0.95
0.16
127
300476
0
2
0.00
1.34
0.95
0.16
300477
0
2
0.00
1.34
0.95
0.16
300478
0
2
0.00
1.34
0.95
0.16
300479
0
2
0.00
1.34
0.95
0.16
300480
0
2
0.00
1.34
0.95
0.16
300481
0
2
0.00
1.34
0.95
0.16
300482
0
2
0.00
1.34
0.95
0.16
300483
0
2
0.00
1.34
0.95
0.16
0.0
3
0.00
0.0
0.00
0.50
Bearden
Silty
Clay
Loam;
Hydrologic
Group
C;
100.00
0
0
0
0
0
0
0
0
0
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
4
1
10.00
1.400
0.377
0.000
0.000
0.58
0.58
0.00
0.10
0.377
0.207
1.160
3.0
2
8.00
1.400
0.377
0.000
0.000
0.029
0.029
0.00
1.00
0.377
0.207
1.160
3.0
3
54.00
1.500
0.292
0.000
0.000
0.029
0.029
0.00
2.00
0.292
0.132
1.160
3.0
4
28.00
1.800
0.285
0.000
0.000
0.029
0.029
0.00
2.0
0.285
0.125
0.174
3.0
0
YEAR
5
YEAR
5
YEAR
5
1
1
1
1
YEAR
***
PRCP
TSER
0
0***
RUNF
TCUM
0
0
***
ESLS
TSER
0
0
1.0E3***
***
RFLX
TSER
0
0
1.0E5***
***
EFLX
TSER
0
0
1.0E5***
***
RZFX
TSER
0
0
1.0E5***
128
Maximum
Application
Rate:
Florida
Citrus,
Index
Reservoir
PRZM3
Input
File,
flcit.
inp
(Jan
28
2000)
***
original
file
source
unknown
***
***
Source
of
crop
and
soil
data
unknown
***
***
modified
for
carbaryl
by
Laurence
Libelo,
6/
21/
00
***
Location:
Osceola
County,
FL.;
Crop:
citrus;
MLRA
156A
0.77
0.15
0
25.00
1
1
4
0.10
0.13
1.00
172.8
3
1.00
600.0
1
1
0.10
100.00
80.00
3
94
84
89
0.00
100.00
1
3
0101
21
9
2209
0.10
0.10
0.10
.023
.023
.023
36
110548
170748
10848
1
110549
170749
10849
1
110550
170750
10850
1
110551
170751
10851
1
110552
170752
10852
1
110553
170753
10853
1
110554
170754
10854
1
110555
170755
10855
1
110556
170756
10856
1
110557
170757
10857
1
110558
170758
10858
1
110559
170759
10859
1
110560
170760
10860
1
110561
170761
10861
1
110562
170762
10862
1
110563
170763
10863
1
110564
170764
10864
1
110565
170765
10865
1
110566
170766
10866
1
110567
170767
10867
1
110568
170768
10868
1
110569
170769
10869
1
110570
170770
10870
1
110571
170771
10871
1
110572
170772
10872
1
110573
170773
10873
1
110574
170774
10874
1
110575
170775
10875
1
110576
170776
10876
1
110577
170777
10877
1
110578
170778
10878
1
110579
170779
10879
1
110580
170780
10880
1
129
110581
170781
10881
1
110582
170782
10882
1
110583
170783
10883
1
Application:
4
aerial
appls
@
5
lb
a.
i./
ac/
year
(5.6
kg/
ha)
@95%
eff,
w/
16%
drift
144
1
0
0
CARBARYL
on
FL
Cirtus
300448
0
2
0.00
5.60
0.95
0.16
140548
0
2
0.00
5.60
0.95
0.16
280548
0
2
0.00
5.60
0.95
0.16
110648
0
2
0.00
5.60
0.95
0.16
300449
0
2
0.00
5.60
0.95
0.16
140549
0
2
0.00
5.60
0.95
0.16
280549
0
2
0.00
5.60
0.95
0.16
110649
0
2
0.00
5.60
0.95
0.16
300450
0
2
0.00
5.60
0.95
0.16
140550
0
2
0.00
5.60
0.95
0.16
280550
0
2
0.00
5.60
0.95
0.16
110650
0
2
0.00
5.60
0.95
0.16
300451
0
2
0.00
5.60
0.95
0.16
140551
0
2
0.00
5.60
0.95
0.16
280551
0
2
0.00
5.60
0.95
0.16
110651
0
2
0.00
5.60
0.95
0.16
300452
0
2
0.00
5.60
0.95
0.16
140552
0
2
0.00
5.60
0.95
0.16
280552
0
2
0.00
5.60
0.95
0.16
110652
0
2
0.00
5.60
0.95
0.16
300453
0
2
0.00
5.60
0.95
0.16
140553
0
2
0.00
5.60
0.95
0.16
280553
0
2
0.00
5.60
0.95
0.16
110653
0
2
0.00
5.60
0.95
0.16
300454
0
2
0.00
5.60
0.95
0.16
140554
0
2
0.00
5.60
0.95
0.16
280554
0
2
0.00
5.60
0.95
0.16
110654
0
2
0.00
5.60
0.95
0.16
300455
0
2
0.00
5.60
0.95
0.16
140555
0
2
0.00
5.60
0.95
0.16
280555
0
2
0.00
5.60
0.95
0.16
110655
0
2
0.00
5.60
0.95
0.16
300456
0
2
0.00
5.60
0.95
0.16
140556
0
2
0.00
5.60
0.95
0.16
280556
0
2
0.00
5.60
0.95
0.16
110656
0
2
0.00
5.60
0.95
0.16
300457
0
2
0.00
5.60
0.95
0.16
140557
0
2
0.00
5.60
0.95
0.16
280557
0
2
0.00
5.60
0.95
0.16
110657
0
2
0.00
5.60
0.95
0.16
300458
0
2
0.00
5.60
0.95
0.16
140558
0
2
0.00
5.60
0.95
0.16
280558
0
2
0.00
5.60
0.95
0.16
110658
0
2
0.00
5.60
0.95
0.16
130
300459
0
2
0.00
5.60
0.95
0.16
140559
0
2
0.00
5.60
0.95
0.16
280559
0
2
0.00
5.60
0.95
0.16
110659
0
2
0.00
5.60
0.95
0.16
300460
0
2
0.00
5.60
0.95
0.16
140560
0
2
0.00
5.60
0.95
0.16
280560
0
2
0.00
5.60
0.95
0.16
110660
0
2
0.00
5.60
0.95
0.16
300461
0
2
0.00
5.60
0.95
0.16
140561
0
2
0.00
5.60
0.95
0.16
280561
0
2
0.00
5.60
0.95
0.16
110661
0
2
0.00
5.60
0.95
0.16
300462
0
2
0.00
5.60
0.95
0.16
140562
0
2
0.00
5.60
0.95
0.16
280562
0
2
0.00
5.60
0.95
0.16
110662
0
2
0.00
5.60
0.95
0.16
300463
0
2
0.00
5.60
0.95
0.16
140563
0
2
0.00
5.60
0.95
0.16
280563
0
2
0.00
5.60
0.95
0.16
110663
0
2
0.00
5.60
0.95
0.16
300464
0
2
0.00
5.60
0.95
0.16
140564
0
2
0.00
5.60
0.95
0.16
280564
0
2
0.00
5.60
0.95
0.16
110664
0
2
0.00
5.60
0.95
0.16
300465
0
2
0.00
5.60
0.95
0.16
140565
0
2
0.00
5.60
0.95
0.16
280565
0
2
0.00
5.60
0.95
0.16
110665
0
2
0.00
5.60
0.95
0.16
300466
0
2
0.00
5.60
0.95
0.16
140566
0
2
0.00
5.60
0.95
0.16
280566
0
2
0.00
5.60
0.95
0.16
110666
0
2
0.00
5.60
0.95
0.16
300467
0
2
0.00
5.60
0.95
0.16
140567
0
2
0.00
5.60
0.95
0.16
280567
0
2
0.00
5.60
0.95
0.16
110667
0
2
0.00
5.60
0.95
0.16
300468
0
2
0.00
5.60
0.95
0.16
140568
0
2
0.00
5.60
0.95
0.16
280568
0
2
0.00
5.60
0.95
0.16
110668
0
2
0.00
5.60
0.95
0.16
300469
0
2
0.00
5.60
0.95
0.16
140569
0
2
0.00
5.60
0.95
0.16
280569
0
2
0.00
5.60
0.95
0.16
110669
0
2
0.00
5.60
0.95
0.16
300470
0
2
0.00
5.60
0.95
0.16
140570
0
2
0.00
5.60
0.95
0.16
280570
0
2
0.00
5.60
0.95
0.16
110670
0
2
0.00
5.60
0.95
0.16
300471
0
2
0.00
5.60
0.95
0.16
140571
0
2
0.00
5.60
0.95
0.16
280571
0
2
0.00
5.60
0.95
0.16
131
110671
0
2
0.00
5.60
0.95
0.16
300472
0
2
0.00
5.60
0.95
0.16
140572
0
2
0.00
5.60
0.95
0.16
280572
0
2
0.00
5.60
0.95
0.16
110672
0
2
0.00
5.60
0.95
0.16
300473
0
2
0.00
5.60
0.95
0.16
140573
0
2
0.00
5.60
0.95
0.16
280573
0
2
0.00
5.60
0.95
0.16
110673
0
2
0.00
5.60
0.95
0.16
300474
0
2
0.00
5.60
0.95
0.16
140574
0
2
0.00
5.60
0.95
0.16
280574
0
2
0.00
5.60
0.95
0.16
110674
0
2
0.00
5.60
0.95
0.16
300475
0
2
0.00
5.60
0.95
0.16
140575
0
2
0.00
5.60
0.95
0.16
280575
0
2
0.00
5.60
0.95
0.16
110675
0
2
0.00
5.60
0.95
0.16
300476
0
2
0.00
5.60
0.95
0.16
140576
0
2
0.00
5.60
0.95
0.16
280576
0
2
0.00
5.60
0.95
0.16
110676
0
2
0.00
5.60
0.95
0.16
300477
0
2
0.00
5.60
0.95
0.16
140577
0
2
0.00
5.60
0.95
0.16
280577
0
2
0.00
5.60
0.95
0.16
110677
0
2
0.00
5.60
0.95
0.16
300478
0
2
0.00
5.60
0.95
0.16
140578
0
2
0.00
5.60
0.95
0.16
280578
0
2
0.00
5.60
0.95
0.16
110678
0
2
0.00
5.60
0.95
0.16
300479
0
2
0.00
5.60
0.95
0.16
140579
0
2
0.00
5.60
0.95
0.16
280579
0
2
0.00
5.60
0.95
0.16
110679
0
2
0.00
5.60
0.95
0.16
300480
0
2
0.00
5.60
0.95
0.16
140580
0
2
0.00
5.60
0.95
0.16
280580
0
2
0.00
5.60
0.95
0.16
110680
0
2
0.00
5.60
0.95
0.16
300481
0
2
0.00
5.60
0.95
0.16
140581
0
2
0.00
5.60
0.95
0.16
280581
0
2
0.00
5.60
0.95
0.16
110681
0
2
0.00
5.60
0.95
0.16
300482
0
2
0.00
5.60
0.95
0.16
140582
0
2
0.00
5.60
0.95
0.16
280582
0
2
0.00
5.60
0.95
0.16
110682
0
2
0.00
5.60
0.95
0.16
300483
0
2
0.00
5.60
0.95
0.16
140583
0
2
0.00
5.60
0.95
0.16
280583
0
2
0.00
5.60
0.95
0.16
110683
0
2
0.00
5.60
0.95
0.16
0.
1
132
0.00
0.000
0.50
Soil
Series:
Adamsville
sand;
Hydrogic
Group
C
***
Kd
for
sandy
loam
=
1.7
100.00
0
0
0
0
0
0
0
0
0
00.0
0.00
00.00
3
1
10.000
1.440
0.086
0.000
0.000
0.000
.058
.058
0.000
0.100
0.086
0.036
0.580
1.7
2
10.000
1.440
0.086
0.000
0.000
0.000
.029
.029
0.000
1.000
0.086
0.036
0.580
1.7
3
80.000
1.580
0.030
0.000
0.000
0.000
.029
.029
0.000
5.000
0.030
0.023
0.116
1.7
0
WATR
YEAR
10
PEST
YEAR
10
CONC
YEAR
10
1
6
11
1
DAY
RUNF
TSER
0
0
1.
E0
133
Average
Application
Rate:
Florida
Citrus,
Index
Reservoir
PRZM3
Input
File,
flcit.
inp
(Jan
28
2000)
***
original
file
source
unknown
***
***
Source
of
crop
and
soil
data
unknown
***
***
modified
for
carbaryl
by
Laurence
Libelo,
6/
21/
00
***
Location:
Osceola
County,
FL.;
Crop:
citrus;
MLRA
156A
0.77
0.15
0
25.00
1
1
4
0.10
0.13
1.00
172.8
3
1.00
600.0
1
1
0.10
100.00
80.00
3
94
84
89
0.00
100.00
1
3
0101
21
9
2209
0.10
0.10
0.10
.023
.023
.023
36
110548
170748
10848
1
110549
170749
10849
1
110550
170750
10850
1
110551
170751
10851
1
110552
170752
10852
1
110553
170753
10853
1
110554
170754
10854
1
110555
170755
10855
1
110556
170756
10856
1
110557
170757
10857
1
110558
170758
10858
1
110559
170759
10859
1
110560
170760
10860
1
110561
170761
10861
1
110562
170762
10862
1
110563
170763
10863
1
110564
170764
10864
1
110565
170765
10865
1
110566
170766
10866
1
110567
170767
10867
1
110568
170768
10868
1
110569
170769
10869
1
110570
170770
10870
1
110571
170771
10871
1
110572
170772
10872
1
110573
170773
10873
1
110574
170774
10874
1
110575
170775
10875
1
110576
170776
10876
1
110577
170777
10877
1
110578
170778
10878
1
110579
170779
10879
1
110580
170780
10880
1
134
110581
170781
10881
1
110582
170782
10882
1
110583
170783
10883
1
Application
=
average
2
aps
@
3.4
lb
A.
I./
acre
***
Application:
4
aerial
appls
@
5
lb
a.
i./
ac/
year
(5.6
kg/
ha)
@95%
eff,
w/
16%
drift
72
1
0
0
CARBARYL
on
FL
Cirtus
300448
0
2
0.00
3.81
0.95
0.16
170548
0
2
0.00
3.81
0.95
0.16
300449
0
2
0.00
3.81
0.95
0.16
170549
0
2
0.00
3.81
0.95
0.16
300450
0
2
0.00
3.81
0.95
0.16
170550
0
2
0.00
3.81
0.95
0.16
300451
0
2
0.00
3.81
0.95
0.16
170551
0
2
0.00
3.81
0.95
0.16
300452
0
2
0.00
3.81
0.95
0.16
170552
0
2
0.00
3.81
0.95
0.16
300453
0
2
0.00
3.81
0.95
0.16
170553
0
2
0.00
3.81
0.95
0.16
300454
0
2
0.00
3.81
0.95
0.16
170554
0
2
0.00
3.81
0.95
0.16
300455
0
2
0.00
3.81
0.95
0.16
170555
0
2
0.00
3.81
0.95
0.16
300456
0
2
0.00
3.81
0.95
0.16
170556
0
2
0.00
3.81
0.95
0.16
300457
0
2
0.00
3.81
0.95
0.16
170557
0
2
0.00
3.81
0.95
0.16
300458
0
2
0.00
3.81
0.95
0.16
170558
0
2
0.00
3.81
0.95
0.16
300459
0
2
0.00
3.81
0.95
0.16
170559
0
2
0.00
3.81
0.95
0.16
300460
0
2
0.00
3.81
0.95
0.16
170560
0
2
0.00
3.81
0.95
0.16
300461
0
2
0.00
3.81
0.95
0.16
170561
0
2
0.00
3.81
0.95
0.16
300462
0
2
0.00
3.81
0.95
0.16
170562
0
2
0.00
3.81
0.95
0.16
300463
0
2
0.00
3.81
0.95
0.16
170563
0
2
0.00
3.81
0.95
0.16
300464
0
2
0.00
3.81
0.95
0.16
170564
0
2
0.00
3.81
0.95
0.16
300465
0
2
0.00
3.81
0.95
0.16
170565
0
2
0.00
3.81
0.95
0.16
300466
0
2
0.00
3.81
0.95
0.16
170566
0
2
0.00
3.81
0.95
0.16
300467
0
2
0.00
3.81
0.95
0.16
170567
0
2
0.00
3.81
0.95
0.16
300468
0
2
0.00
3.81
0.95
0.16
170568
0
2
0.00
3.81
0.95
0.16
300469
0
2
0.00
3.81
0.95
0.16
135
170569
0
2
0.00
3.81
0.95
0.16
300470
0
2
0.00
3.81
0.95
0.16
170570
0
2
0.00
3.81
0.95
0.16
300471
0
2
0.00
3.81
0.95
0.16
170571
0
2
0.00
3.81
0.95
0.16
300472
0
2
0.00
3.81
0.95
0.16
170572
0
2
0.00
3.81
0.95
0.16
300473
0
2
0.00
3.81
0.95
0.16
170573
0
2
0.00
3.81
0.95
0.16
300474
0
2
0.00
3.81
0.95
0.16
170574
0
2
0.00
3.81
0.95
0.16
300475
0
2
0.00
3.81
0.95
0.16
170575
0
2
0.00
3.81
0.95
0.16
300476
0
2
0.00
3.81
0.95
0.16
170576
0
2
0.00
3.81
0.95
0.16
300477
0
2
0.00
3.81
0.95
0.16
170577
0
2
0.00
3.81
0.95
0.16
300478
0
2
0.00
3.81
0.95
0.16
170578
0
2
0.00
3.81
0.95
0.16
300479
0
2
0.00
3.81
0.95
0.16
170579
0
2
0.00
3.81
0.95
0.16
300480
0
2
0.00
3.81
0.95
0.16
170580
0
2
0.00
3.81
0.95
0.16
300481
0
2
0.00
3.81
0.95
0.16
170581
0
2
0.00
3.81
0.95
0.16
300482
0
2
0.00
3.81
0.95
0.16
170582
0
2
0.00
3.81
0.95
0.16
300483
0
2
0.00
3.81
0.95
0.16
170583
0
2
0.00
3.81
0.95
0.16
0.
1
0.00
0.000
0.50
Soil
Series:
Adamsville
sand;
Hydrogic
Group
C
***
Kd
for
sandy
loam
=
1.7
100.00
0
0
0
0
0
0
0
0
0
00.0
0.00
00.00
3
1
10.000
1.440
0.086
0.000
0.000
0.000
.058
.058
0.000
0.100
0.086
0.036
0.580
1.7
2
10.000
1.440
0.086
0.000
0.000
0.000
.029
.029
0.000
1.000
0.086
0.036
0.580
1.7
3
80.000
1.580
0.030
0.000
0.000
0.000
.029
.029
0.000
5.000
0.030
0.023
0.116
1.7
0
WATR
YEAR
10
PEST
YEAR
10
CONC
YEAR
10
1
6
11
136
1
DAY
RUNF
TSER
0
0
1.
E0
137
Maximum
Reported
Application
Rate:
Florida
Citrus,
Index
Reservoir
PRZM3
Input
File,
flcit.
inp
(Jan
28
2000)
***
original
file
source
unknown
***
***
Source
of
crop
and
soil
data
unknown
***
***
modified
for
carbaryl
by
Laurence
Libelo,
6/
21/
00
***
Location:
Osceola
County,
FL.;
Crop:
citrus;
MLRA
156A
0.77
0.15
0
25.00
1
1
4
0.10
0.13
1.00
172.8
3
1.00
600.0
1
1
0.10
100.00
80.00
3
94
84
89
0.00
100.00
1
3
0101
21
9
2209
0.10
0.10
0.10
.023
.023
.023
36
110548
170748
10848
1
110549
170749
10849
1
110550
170750
10850
1
110551
170751
10851
1
110552
170752
10852
1
110553
170753
10853
1
110554
170754
10854
1
110555
170755
10855
1
110556
170756
10856
1
110557
170757
10857
1
110558
170758
10858
1
110559
170759
10859
1
110560
170760
10860
1
110561
170761
10861
1
110562
170762
10862
1
110563
170763
10863
1
110564
170764
10864
1
110565
170765
10865
1
110566
170766
10866
1
110567
170767
10867
1
110568
170768
10868
1
110569
170769
10869
1
110570
170770
10870
1
110571
170771
10871
1
110572
170772
10872
1
110573
170773
10873
1
110574
170774
10874
1
110575
170775
10875
1
110576
170776
10876
1
110577
170777
10877
1
110578
170778
10878
1
110579
170779
10879
1
138
110580
170780
10880
1
110581
170781
10881
1
110582
170782
10882
1
110583
170783
10883
1
Application
=
maximum
reported
3
aps
@
4.26
lb
A.
I./
acre
***
Application:
4
aerial
appls
@
5
lb
a.
i./
ac/
year
(5.6
kg/
ha)
@95%
eff,
w/
16%
drift
108
1
0
0
CARBARYL
on
FL
Cirtus
300448
0
2
0.00
4.77
0.95
0.16
140548
0
2
0.00
4.77
0.95
0.16
280548
0
2
0.00
4.77
0.95
0.16
300449
0
2
0.00
4.77
0.95
0.16
140549
0
2
0.00
4.77
0.95
0.16
280549
0
2
0.00
4.77
0.95
0.16
300450
0
2
0.00
4.77
0.95
0.16
140550
0
2
0.00
4.77
0.95
0.16
280550
0
2
0.00
4.77
0.95
0.16
300451
0
2
0.00
4.77
0.95
0.16
140551
0
2
0.00
4.77
0.95
0.16
280551
0
2
0.00
4.77
0.95
0.16
300452
0
2
0.00
4.77
0.95
0.16
140552
0
2
0.00
4.77
0.95
0.16
280552
0
2
0.00
4.77
0.95
0.16
300453
0
2
0.00
4.77
0.95
0.16
140553
0
2
0.00
4.77
0.95
0.16
280553
0
2
0.00
4.77
0.95
0.16
300454
0
2
0.00
4.77
0.95
0.16
140554
0
2
0.00
4.77
0.95
0.16
280554
0
2
0.00
4.77
0.95
0.16
300455
0
2
0.00
4.77
0.95
0.16
140555
0
2
0.00
4.77
0.95
0.16
280555
0
2
0.00
4.77
0.95
0.16
300456
0
2
0.00
4.77
0.95
0.16
140556
0
2
0.00
4.77
0.95
0.16
280556
0
2
0.00
4.77
0.95
0.16
300457
0
2
0.00
4.77
0.95
0.16
140557
0
2
0.00
4.77
0.95
0.16
280557
0
2
0.00
4.77
0.95
0.16
300458
0
2
0.00
4.77
0.95
0.16
140558
0
2
0.00
4.77
0.95
0.16
280558
0
2
0.00
4.77
0.95
0.16
300459
0
2
0.00
4.77
0.95
0.16
140559
0
2
0.00
4.77
0.95
0.16
280559
0
2
0.00
4.77
0.95
0.16
300460
0
2
0.00
4.77
0.95
0.16
140560
0
2
0.00
4.77
0.95
0.16
280560
0
2
0.00
4.77
0.95
0.16
300461
0
2
0.00
4.77
0.95
0.16
140561
0
2
0.00
4.77
0.95
0.16
280561
0
2
0.00
4.77
0.95
0.16
139
300462
0
2
0.00
4.77
0.95
0.16
140562
0
2
0.00
4.77
0.95
0.16
280562
0
2
0.00
4.77
0.95
0.16
300463
0
2
0.00
4.77
0.95
0.16
140563
0
2
0.00
4.77
0.95
0.16
280563
0
2
0.00
4.77
0.95
0.16
300464
0
2
0.00
4.77
0.95
0.16
140564
0
2
0.00
4.77
0.95
0.16
280564
0
2
0.00
4.77
0.95
0.16
300465
0
2
0.00
4.77
0.95
0.16
140565
0
2
0.00
4.77
0.95
0.16
280565
0
2
0.00
4.77
0.95
0.16
300466
0
2
0.00
4.77
0.95
0.16
140566
0
2
0.00
4.77
0.95
0.16
280566
0
2
0.00
4.77
0.95
0.16
300467
0
2
0.00
4.77
0.95
0.16
140567
0
2
0.00
4.77
0.95
0.16
280567
0
2
0.00
4.77
0.95
0.16
300468
0
2
0.00
4.77
0.95
0.16
140568
0
2
0.00
4.77
0.95
0.16
280568
0
2
0.00
4.77
0.95
0.16
300469
0
2
0.00
4.77
0.95
0.16
140569
0
2
0.00
4.77
0.95
0.16
280569
0
2
0.00
4.77
0.95
0.16
300470
0
2
0.00
4.77
0.95
0.16
140570
0
2
0.00
4.77
0.95
0.16
280570
0
2
0.00
4.77
0.95
0.16
300471
0
2
0.00
4.77
0.95
0.16
140571
0
2
0.00
4.77
0.95
0.16
280571
0
2
0.00
4.77
0.95
0.16
300472
0
2
0.00
4.77
0.95
0.16
140572
0
2
0.00
4.77
0.95
0.16
280572
0
2
0.00
4.77
0.95
0.16
300473
0
2
0.00
4.77
0.95
0.16
140573
0
2
0.00
4.77
0.95
0.16
280573
0
2
0.00
4.77
0.95
0.16
300474
0
2
0.00
4.77
0.95
0.16
140574
0
2
0.00
4.77
0.95
0.16
280574
0
2
0.00
4.77
0.95
0.16
300475
0
2
0.00
4.77
0.95
0.16
140575
0
2
0.00
4.77
0.95
0.16
280575
0
2
0.00
4.77
0.95
0.16
300476
0
2
0.00
4.77
0.95
0.16
140576
0
2
0.00
4.77
0.95
0.16
280576
0
2
0.00
4.77
0.95
0.16
300477
0
2
0.00
4.77
0.95
0.16
140577
0
2
0.00
4.77
0.95
0.16
280577
0
2
0.00
4.77
0.95
0.16
300478
0
2
0.00
4.77
0.95
0.16
140578
0
2
0.00
4.77
0.95
0.16
280578
0
2
0.00
4.77
0.95
0.16
140
300479
0
2
0.00
4.77
0.95
0.16
140579
0
2
0.00
4.77
0.95
0.16
280579
0
2
0.00
4.77
0.95
0.16
300480
0
2
0.00
4.77
0.95
0.16
140580
0
2
0.00
4.77
0.95
0.16
280580
0
2
0.00
4.77
0.95
0.16
300481
0
2
0.00
4.77
0.95
0.16
140581
0
2
0.00
4.77
0.95
0.16
280581
0
2
0.00
4.77
0.95
0.16
300482
0
2
0.00
4.77
0.95
0.16
140582
0
2
0.00
4.77
0.95
0.16
280582
0
2
0.00
4.77
0.95
0.16
300483
0
2
0.00
4.77
0.95
0.16
140583
0
2
0.00
4.77
0.95
0.16
280583
0
2
0.00
4.77
0.95
0.16
0.
1
0.00
0.000
0.50
Soil
Series:
Adamsville
sand;
Hydrogic
Group
C
***
Kd
for
sandy
loam
=
1.7
100.00
0
0
0
0
0
0
0
0
0
00.0
0.00
00.00
3
1
10.000
1.440
0.086
0.000
0.000
0.000
.058
.058
0.000
0.100
0.086
0.036
0.580
1.7
2
10.000
1.440
0.086
0.000
0.000
0.000
.029
.029
0.000
1.000
0.086
0.036
0.580
1.7
3
80.000
1.580
0.030
0.000
0.000
0.000
.029
.029
0.000
5.000
0.030
0.023
0.116
1.7
0
WATR
YEAR
10
PEST
YEAR
10
CONC
YEAR
10
1
6
11
1
DAY
RUNF
TSER
0
0
1.
E0
APPENDIX
A2:
Results
of
Scigrow
Run
for
Carbaryl
RUN
No.
1
FOR
Carbaryl
INPUT
VALUES
APPL
(#/
AC)
APPL.
URATE
SOIL
SOIL
AEROBIC
RATE
NO.
(#/
AC/
YR)
KOC
METABOLISM
(DAYS)
5.000
4
20.000
211.0
12.0
141
GROUND
WATER
SCREENING
CONCENTRATIONS
IN
PPB
.829154
A=
7.000
B=
216.000
C=
.845
D=
2.334
RILP=
1.408
F=
1.382
G=
.041
URATE=
20.000
GWSC=
.829154
142
Appendix
B:
Ecological
Risk
Assessment
ECOLOGICAL
RISK
ASSESSMENT
Risk
characterization
integrates
the
results
of
exposure
and
ecotoxicity
data
to
evaluate
the
likelihood
of
adverse
ecological
effects,
using
for
this
purpose
the
risk
quotient
(RQ)
method.
RQs
are
calculated
by
dividing
estimated
environmental
concentrations
(EECs)
of
the
pesticide
by
acute
and
chronic
toxicity
values.
Although
EECs
are
primarily
based
on
the
maximum
label
application
rates
for
that
pesticide,
EECs
based
on
QUA
average
and
maximum
reported
(Doane
data)
use
rates
were
also
considered
in
this
assessment.
The
74
carbaryl
registered
uses
and
application
specifications
(methods,
maximum
label
use
rates,
number
of
applications,
and
interval
between
applications)
used
in
the
risk
assessment
for
terrestrial
organisms
are
summarized
in
Table
1.
RQs
are
compared
to
levels
of
concern
(LOC)
criteria
used
by
OPP
for
determining
potential
risk
to
nontarget
organisms
and
the
subsequent
need
for
possible
regulatory
action.
The
criteria
indicate
that
a
pesticide
used
as
directed
has
the
potential
to
cause
adverse
effects
on
nontarget
organisms.
Levels
of
concern
currently
address
the
following
risk
presumption
categories:
(1)
acute
potential
for
acute
risk;
regulatory
action
may
be
warranted
in
addition
to
restricted
use
classification,
(2)
acute
restricted
use
potential
for
acute
risk,
but
may
be
mitigated
through
restricted
use
classification,
(3)
acute
endangered
species
potential
for
acute
risk
to
endangered
species;
regulatory
action
may
be
warranted,
and
(4)
chronic
risk
the
potential
for
chronic
risk
is
high,
and
regulatory
action
may
be
warranted.
Currently,
EFED
does
not
perform
assessments
for
chronic
risk
to
plants,
acute
or
chronic
risks
to
nontarget
insects,
or
chronic
risk
from
granular/
bait
formulations
to
birds
or
mammals.
Risk
presumptions
and
the
corresponding
risk
quotients
and
levels
of
concern
are
summarized
in
Table
2.
In
addition,
the
Agency
considers
any
incident
data
that
is
submitted
concerning
adverse
effects
on
nontarget
species.
143
Table
1.
Uses,
application
rates,
and
application
intervals
used
in
the
risk
assessment
for
carbaryl
1
Uses
Non
granular
Formulations
Granular/
Bait
Use/
Crop
Appl
Rate
(lb
ai/
A)
No.
Appl
Interval
(days)
Max
lb/
year
Rate
(lb
ai/
A)
Asparagus
2
5
3
10
2
Broccoli,
Brussels
sprouts,
cauliflower,
collards,
cabbage,
mustard
greens,
lettuce,
parsley,
spinach,
celery,
Swiss
chard,
(beets,
carrots,
potato,
radish,
horseradish,
parsnip,
rutabaga,
salsify
2
37
62
Corn
(field,
pop)
2
4
14
8
Sorghum
2
3
7
6
Rice
(tadpole
shrimp)
1.
5
2
7
4
Corn
(sweet)
2
8
3
16
2
Flax,
millet,
wheat,
pasture,
grasses,
noncropland,
1.5
2
14
3
Cucurbits
(melons,
cucumbers,
squash,
pumpkin)
1
6
7
6
Alfalfa,
clover
1.
5
8
30
12
Rangeland
1
1
1
Solanaceous
crops
(tomato,
pepper,
eggplant),
tobacco
2
4
7
8
2
Legumes
(beans,
peas,
lentils,
cowpeas,
soybean)
1.5
4
7
6
Peanuts,
sweet
potatoes
2
4
7
8
Sugar
beets
1.
5
2
14
4
1.5
Small
fruits
&
berries
(grape,
blueberry,
caneberry,
cranberry,
strawberry)
2
5
7
10
Strawberry
2
Sunflower
1.
5
2
7
3
Citrus
(orange,
lemon,
grapefruit)
5,
16
4
14
20
Olives
7.
5
2
14
15
Pome
fruits
(apple,
pear)
3
5
14
15
Stone
fruits
(peach,
apricot,
cherry,
nectarine,
plum/
prune)
4
3
14
14
Tree
nuts
(almond,
chestnut,
filbert,
pecan,
pistachios,
walnut)
5
3
7
15
Forested
areas
(non
urban)
1
2
7
2
Trees
and
ornamentals
1
6
7
6
9.
1
Turfgrass
8
2
7
16
9.1
Ticks
9.
1
Oyster
beds
1
10
1
Aerial
and
ground
application
methods
for
all
uses
144
Table
2.
Risk
presumptions
for
terrestrial
animals
Risk
Presumption
Risk
Quotient
(RQ)
Level
of
Concern
(LOC)
Birds
Acute
Risk
EEC
1
/LC50
or
LD50/
sqft
2
or
LD50/
day
3
0.5
Acute
Restricted
Use
EEC/
LC50
or
LD50/
sqft
or
LD50/
day
(or
LD50
<
50
mg/
kg)
0.2
Acute
Endangered
Species
EEC/
LC50
or
LD50/
sqft
or
LD50/
day
0.1
Chronic
Risk
EEC/
NOAEC
1
Wild
Mammals
Acute
Risk
EEC/
LC50
or
LD50/
sqft
or
LD50/
day
0.5
Acute
Restricted
Use
EEC/
LC50
or
LD50/
sqft
or
LD50/
day
(or
LD50
<
50
mg/
kg)
0.2
Acute
Endangered
Species
EEC/
LC50
or
LD50/
sqft
or
LD50/
day
0.1
Chronic
Risk
EEC/
NOAEC
1
1
abbreviation
for
Estimated
Environmental
Concentration
(ppm)
on
avian/
mammalian
food
items
2
mg/
ft
2
3
mg
of
toxicant
consumed/
day
LD50
*
wt.
of
bird
LD50
*
wt.
of
bird
Risk
presumptions
for
aquatic
animals
Risk
Presumption
RQ
LOC
Acute
Risk
EEC
1
/LC50
or
EC50
0.5
Acute
Restricted
Use
EEC/
LC50
or
EC50
0.1
Acute
Endangered
Species
EEC/
LC50
or
EC50
0.05
Chronic
Risk
EEC/
NOAEC
1
1
EEC
=
(ppm
or
ppb)
in
water
Risk
presumptions
for
plants
Risk
Presumption
RQ
LOC
Plant
Inhabiting
Terrestrial
and
Semi
Aquatic
Areas
Acute
Risk
EEC
1
/EC25
1
Acute
Endangered
Species
EEC/
EC05
or
NOAEC
1
Aquatic
Plants
Acute
Risk
EEC
2
/EC50
1
Acute
Endangered
Species
EEC/
EC05
or
NOAEC
1
1
EEC
=
lbs
a.
i./
A
2
EEC
=
(ppb
or
ppm)
in
water
145
Exposure
and
Risk
to
Nontarget
Terrestrial
Animals
For
nongranular
pesticide
applications
(e.
g.,
liquid,
dust),
the
estimated
environmental
concentrations
(EECs)
on
food
items
following
product
application
are
compared
to
LC50
values
to
assess
risk.
The
predicted
0
day
maximum
and
mean
residues
of
a
pesticide
that
may
be
expected
to
occur
on
selected
avian
or
mammalian
food
items
immediately
following
a
direct
single
application
at
1
lb
a.
i./
A
are
tabulated
in
Table
3.
Table
3.
Estimated
environmental
concentrations
(EECs)
on
avian
and
mammalian
food
items
(ppm)
following
a
single
application
at
1
lb
a.
i./
A)
Food
Items
EEC
(ppm)
Predicted
Maximum
Residue
1
EEC
(ppm)
Predicted
Mean
Residue
1
Short
grass
240
85
Tall
grass
110
36
Broadleaf/
forage
plants
and
small
insects
135
45
Fruits,
pods,
seeds,
and
large
insects
15
7
1
Predicted
maximum
and
mean
residues
are
for
a
1
lb
a.
i./
a
application
rate
and
are
based
on
Hoerger
and
Kenaga
(1972)
as
modified
by
Fletcher
et
al.
(1994).
The
following
toxicity
endpoints
are
used
in
the
risk
assessment
of
carbaryl:
Avian
acute
oral
LD50
rock
dove
=
1000
mg/
kg
Avian
subacute
dietary
LC50
bobwhite
quail
=
>5000
ppm
Avian
chronic
(reproduction)
NOAEC
mallard
duck
=
300
ppm
Mammalian
acute
oral
LD50
rat
=
301
mg/
kg
Mammalian
chronic
(reproduction)
NOAEC
rat
=
80
ppm
Freshwater
fish
acute
LC50
salmon
=
0.25
ppm
Freshwater
fish
acute
(TEP)
LC50
trout
=
1.2
ppm
Freshwater
fish
chronic
NOAEC
minnow
=
0.21
ppm
Freshwater
invertebrate
acute
LC50
stonefly
=
1.7
ppb
Freshwater
invertebrate
chronic
NOAEC
waterflea
=
1.5
ppb
Estuarine/
marine
fish
acute
LC50
minnow
=
2.6
ppm
Estuarine/
marine
mollusc
acute
EC50
oyster
=
2.7
ppm
Estuarine/
marine
shrimp
EC50
mysid
=
5.7
ppb
Estuarine/
marine
fish
chronic
NOAEC
no
data
Estuarine/
marine
aquatic
invertebrate
chronic
NOAEC
no
data
146
Avian
Acute
and
Chronic
Risk
Risk
from
Exposure
to
Nongranular
Products
Since
the
avian
LC50
is
greater
than
5,000
ppm
(Appendix
C),
with
zero
mortality
observed
at
this
concentration
for
the
four
avian
species
tested,
carbaryl
is
classified
as
practically
nontoxic
to
birds,
and
the
avian
LC50
value
for
carbaryl
can
be
considered
a
NOAEC
value.
Therefore,
for
the
avian
risk
assessment,
acute
RQs
for
nongranular
carbaryl
are
compared
to
an
acute
risk
LOC
of
1,
rather
than
to
the
established
avian
risk
LOCs
shown
in
Table
2.
On
this
basis,
no
avian
acute
risk
LOCs
are
exceeded
for
nongranular
carbaryl
at
maximum
label
application
rates
(Table
4).
Based
on
an
avian
NOAEC
of
300
ppm
and
maximum
label
application
rates,
the
avian
chronic
risk
LOC
is
exceeded
for
most
nongranular
uses
(Table
4).
For
birds
feeding
on
short
grasses,
the
avian
chronic
risk
LOC
is
exceeded
for
all
uses,
except
rangeland.
For
tall
grass
feeders,
the
avian
chronic
LOC
is
exceeded
for
all
uses,
except
sugar
beets,
wheat,
millet,
flax,
pasture,
grasses,
noncropland,
rangeland,
and
non
urban
forested
areas.
For
birds
feeding
on
broadleaf/
forage
plants
and
small
insects
the
avian
chronic
LOC
is
exceeded
for
all
uses
except
for
rangeland
and
non
urban
forested
areas.
The
chronic
LOC
for
birds
feeding
on
fruits,
pods,
seeds,
and
large
insects
is
not
exceeded
for
any
of
the
carbaryl
uses.
In
addition
to
maximum
label
use
rates,
avian
acute
and
chronic
RQs
were
also
calculated
for
nongranular
carbaryl
using
QUA
average
use
rates
(Table
5a)
for
70
use
sites,
as
well
as
maximum
reported
(Doane
data)
use
rates
for
42
use
sites
(Table
5b).
The
acute
risk
LOCs
are
not
exceeded
for
any
nongranular
carbaryl
use
at
less
than
maximum
label
use
rates.
When
RQs
are
based
on
average
application
rates,
the
chronic
risk
LOC
is
exceeded
for
39
of
70
uses.
For
RQs
based
on
maximum
reported
use
rates,
the
chronic
risk
LOC
is
met
or
exceeded
for
34
of
42
uses
(Table
5b).
147
Table
4.
Avian
acute
and
chronic
RQs
for
multiple
applications
of
nongranular
carbaryl
(broadcast)
based
on
a
bobwhite
quail
LC50
of
>5000
ppm,
a
mallard
duck
NOAEC
of
300
ppm,
and
maximum
label
application
rates.
Uses
Appl.
Rate
No.
Appl.
Interval
Food
Items
Maximum
EEC
1
(ppm)
LC50
(ppm)
NOAEC
(ppm)
Acute
RQ
(EEC/
LC50)
Chron.
RQ
(EEC/
NOAEC)
Citrus
(orange,
lemon,
grapefruit)
5
lb
ai/
A
4
appl
14
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
3320.98
1522.12
1868.05
207.56
>5000
300
<0.66
<0.30
<0.37
<0.04
11.07
5.07
6.23
0.69
Citrus
(California)
16
lb
ai/
A
1
appl
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
3840.00
1760.00
2160.00
240.00
>5000
300
<0.77
<0.35
<0.43
<0.05
12.80
5.87
7.20
0.80
Olives
7.5
lb
ai/
A
2
appl
14
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
3164.15
1450.23
1779.83
197.76
>5000
300
<0.63
<0.29
<0.36
<0.04
10.55
4.83
5.93
0.66
Pome
fruits
(apple,
pear)
3
lb
ai/
A
5
appl
14
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
2230.10
1022.13
1254.43
139.38
>5000
300
<0.45
<0.20
<0.25
<0.03
7.43
3.41
4.18
0.46
Stone
fruits
(peaches,
apricot,
cherry,
nectarine,
plum/
prune)
4
lb
ai/
A
3
appl
14
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
2238.92
1026.17
1259.39
139.93
>5000
300
<0.45
<0.21
<0.25
<0.03
7.46
3.42
4.20
0.47
Tree
nuts
(almond,
chestnut,
filbert,
pecan,
pistachios,
walnut)
5
lb
ai/
A
3
appl
7
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
3154.09
1445.62
1774.18
197.13
>5000
300
<0.63
<0.29
<0.35
<0.04
10.51
4.82
5.91
0.66
Corn
(field,
pop)
2
lb
ai/
A
4
appl
14
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
1328.39
608.85
747.22
83.02
>5000
300
<0.27
<0.12
<0.15
<0.02
4.43
2.03
2.49
0.28
Corn
(sweet)
2
lb
ai/
A
8
appl
3
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
3148.03
1442.85
1770.77
196.75
>5000
300
<0.63
<0.29
<0.35
<0.04
10.49
4.81
5.90
0.66
Rice,
sunflower
1.
5
lb
ai/
A
2
appl
7
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
673.40
308.64
378.79
42.09
>5000
300
<0.13
<0.06
<0.08
<0.01
2.24
1.03
1.26
0.14
Sugar
beets,
wheat,
millet,
flax,
pasture,
grasses,
noncropland
1.5
lb
ai/
A
2
appl
14
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
632.83
290.05
355.97
39.55
>5000
300
<0.13
<0.06
<0.07
<0.01
2.11
0.97
1.19
0.13
Asparagus
2
lb
ai/
A
5
appl
3
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
2138.64
980.21
1202.99
133.67
>5000
300
<0.43
<0.20
<0.24
<0.03
7.13
3.27
4.01
0.45
148
Broccoli,
Brussels
sprouts,
cabbage,
cauliflower,
collards,
mustard
greens,
celery,
lettuce,
parsley,
spinach,
beets,
potato,
carrot,
horseradish,
parsnip,
rutabaga,
salsify,
sorghum
2
lb
ai/
A
3
appl
7
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
1261.64
578.25
709.67
78.85
>5000
300
<0.25
<0.12
<0.14
<0.02
4.21
1.93
2.37
0.26
Table
4.
Avian
acute
and
chronic
RQs
for
multiple
applications
of
nongranular
carbaryl
(broadcast)
based
on
a
bobwhite
quail
LC50
of
>5000
ppm,
a
mallard
duck
NOAEC
of
300
ppm,
and
maximum
label
application
rates.
Uses
Appl.
Rate
No.
Appl.
Interval
Food
Items
Maximum
EEC
1
(ppm)
LC50
(ppm)
NOAEC
(ppm)
Acute
RQ
(EEC/
LC50)
Chron.
RQ
(EEC/
NOAEC)
Cucurbits
(cucumbers,
melons,
squash,
pumpkin),
trees
and
ornamentals
1
lb
ai/
A
6
appl
7
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
1047.00
479.88
588.94
65.44
>5000
300
<0.21
<0.10
<0.12
<0.01
3.49
1.60
1.96
0.22
Solanaceous
(tomato,
pepper,
eggplant),
peanuts,
tobacco,
sweet
potato
2
lb
ai/
A
4
appl
7
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
1578.32
723.40
887.80
98.64
>5000
300
<0.32
<0.14
<0.18
<0.02
5.26
2.41
2.96
0.33
Legumes
(beans,
peas,
lentils,
cowpeas,
soybeans)
1.5
lb
ai/
A
4
appl
7
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
1183.74
542.55
665.85
73.98
>5000
300
<0.24
<0.11
<0.13
<0.01
3.95
1.81
2.22
0.25
Small
fruits
&
berries
(grapes,
blueberry,
caneberry,
cranberry,
strawberry)
2
lb
ai/
A
5
appl
7
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
1854.01
849.75
1042.88
115.88
>5000
300
<0.37
<0.17
<0.21
<0.02
6.18
2.83
3.48
0.39
Alfalfa,
clover
1.
5
lb
ai/
A
8
appl
30
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
796.72
365.16
448.15
49.79
>5000
300
<0.16
<0.07
<0.09
<0.01
2.66
1.22
1.49
0.17
Rangeland
1
lb
ai/
A
1
appl
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
240.00
110.00
135.00
15.00
>5000
300
<0.05
<0.02
<0.03
<0.00
0.80
0.37
0.45
0.05
Forested
areas
(non
urban)
1
lb
ai/
A
2
appl
7
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
448.93
205.76
252.52
28.06
>5000
300
<0.09
<0.04
<0.05
<0.01
1.5
0.69
0.84
0.09
Turfgrass
8
lb
ai/
A
2
appl
7
days
Short
grass
Tall
grass
Broadleaf
plants,
sm.
ins.
Fruit,
seeds,
lg.
insects
3591.46
1646.08
2020.19
224.47
5000
300
<0.72
<0.33
<0.40
<0.04
11.97
5.49
6.73
0.75
1
Predicted
maximum
residues
are
for
a
1
lb
a.
i./
a
application
rate
and
are
based
on
Hoerger
and
Kenaga
(1972)
as
modified
by
Fletcher
et
al.
(1994).
149
Table
5a.
Avian
acute
and
chronic
risk
quotients
1
for
multiple
applications
of
nongranular
carbaryl
based
on
a
bobwhite
quail
LC50
of
>5000
ppm
and,
a
mallard
duck
NOAEC
of
300
ppm,
and
QUA
average
application
rates
for
70
uses
Use
site
(Appl.
Rate
[lb
ai/
A],
No.
Applications,
Interval)
Acute
RQ
(EEC/
LC50)
Chronic
RQ
(EEC/
NOAEC)
Use
Site
Acute
RQ
(EEC/
LC50
)
Chronic
RQ
(EEC/
NOAEC)
Alfalfa
(1.
1,
1)
Almonds
(2.
1,
1)
Apples
(1.
2,
1)
Asparagus
(0.
9,
1)
Beans,
Dry
(0.
5,
1)
Beans,
Lima,
Fresh
(0.
9,
1)
Beans,
Snap,
Fresh
(0.
9,
2,
7)
Beans,
Snap,
Processed
(0.
7,
2,
7)
Beets
(0.
5,
1)
Blackberries
(1.
7,
1)
Blueberries
(1.
7,
1)
Broccoli
(0.
8,
1)
Brussels
Sprouts
(0.
9,
1)
Chinese
Cabbage
(0.
2,
1)
Fresh
Cabbage
(1.
0,
2,
7)
Cantaloupes
(0.
8,
1)
Carrots
(0.
9,
2,
7)
Cauliflower
(1.1,
1)
Celery
(1.
0,
2,
7)
Cherries
(1.
9,
1)
Citrus,
other
(1.
8,
2,
14)
Corn,
Field
(1.
0,
1)
Cranberries
(2.
0,
1)
Cucumbers
(1.1,
1)
Cucumbers,
Processed
(0.
6,
2,
7)
Eggplant
(1.
0,
2,
7)
Flax
(1.
1,
1)
Grapefruit
(1.
4,
2,
14)
Grapes
(1.
4,
2,
7)
Hay
(0.
8,
1)
Hazelnuts
(2.5,
1)
Lemons
(2.
7,
1)
Lettuce
(1.
1,
1)
Lots/
Farmsteads
(0.4,
2,
14)
Melons
(0.
7,
1)
<0.05
<0.10
<0.06
<0.04
<0.02
<0.04
<0.08
<0.06
<0.02
<0.08
<0.08
<0.04
<0.04
<0.01
<0.09
<0.04
<0.08
<0.05
<0.09
<0.09
<0.15
<0.05
<0.10
<0.05
<0.05
<0.09
<0.05
<0.12
<0.13
<0.04
<0.12
<0.13
<0.05
<0.04
<0.03
0.88
1.68
0.96
0.72
0.40
0.72
1.35
1.05
0.40
1.36
1.36
0.64
0.72
0.16
1.50
0.64
1.35
0.88
1.50
1.52
2.53
0.80
1.60
0.88
0.90
1.50
0.88
1.97
2.10
0.64
2.00
2.16
0.88
0.75
0.56
Nectarines
(3.8,
1)
Okra
(1.
9,
1)
Olives
(5.
3,
1)
Oranges
(3.
4,
1)
Pasture
(0.
9,
1)
Peaches
(1.0,
3,
7)
Peanuts
(0.
8,
1)
Pears
(1.
0,
1,
2
Pears,
Dry
(1.
0,
1)
Peas,
Green
(1.
5,
1)
Pecans
(1.4,
2)
Peppers,
Bell
(0.
9,
2)
Peppers,
Sweet
(1.
3,
1)
Pistachios
(3.6,
1)
Plums
(3.
8,
1)
Potatoes
(0.
8,
2)
Pumpkins
(2.
0,
2)
Raspberries
(2.
8,
1)
Rice
(1.
1,
1)
Sorghum
(1.
1,
1)
Soybeans
(0.
9,
1)
Squash
(1.
4,
1)
Strawberries
(1.
4,
2)
Sugar
Beets
(1.
3,
1)
Sunflower
(0.
7,
1)
Sweet
Corn,
Fresh
(1.
3,
3,
3)
Sweet
Potatoes
(1.
6,
1)
Tobacco
(1.1,
2,7)
Tomatoes,
Fresh
(0.
7,
3,
7)
Tomatoes,
Processed
(1.
2,
1)
Walnuts
(1.
9,
1)
Watermelons
(0.
5,
1)
Wheat,
Spring
(0.
6,
1)
Wheat,
Winter
(0.
8,
1)
Woodland
(0.
7,
1)
<0.18
<0.09
<0.25
<0.16
<0.04
<0.13
<0.04
<0.08
<0.05
<0.07
<0.13
<0.08
<0.06
<0.17
<0.18
<0.07
<0.18
<0.13
<0.05
<0.05
<0.04
<0.07
<0.13
<0.06
<0.02
<0.18
<0.08
<0.09
<0.09
<0.06
<0.09
<0.02
<0.03
<0.04
<0.02
3.04
1.52
4.24
2.72
0.72
2.10
0.64
1.41
0.80
1.20
2.10
1.35
1.04
2.88
3.04
1.20
2.99
2.24
0.88
0.88
0.72
1.12
2.10
1.04
0.32
2.94
1.28
1.50
1.47
0.96
1.52
0.40
0.48
0.64
0.32
1
Only
the
highest
RQs
i.
e.
those
based
on
short
grass
EECs
are
included
in
this
table.
150
Table
5b.
Avian
highest
acute
and
chronic
risk
quotients
1
for
multiple
applications
of
nongranular
carbaryl
based
on
a
bobwhite
quail
LC50
of
>5000
ppm
and,
a
mallard
duck
NOAEC
of
300
ppm,
and
maximum
reported
use
rates
(Doane
data)
for
42
use
sites
Use
site
[appl.
rate
(lb
ai/
A),
No.
appl]
Acute
RQ
(EEC/
LC50)
Chronic
RQ
(EEC/
NOAEC)
Use
Site
[appl.
rate
(lb
ai/
A)
No.
appl]
Acute
RQ
(EEC/
LC50
)
Chronic
RQ
(EEC/
NOAEC)
Alfalfa
(1.
5,
1)
Almonds
(4,
1)
Apples
(3.
2,
1)
Apricots
(4,
1)
Asparagus
(4,
1)
Beans,
Lima,
(1.
3,
1)
Beans,
snap
(1.
6,
1)
Cabbage
(2,
1)
Canola
(0.
5,
1)
Cantaloupe
(1.
2,
1)
Carrots
(0.
8,
1)
Cauliflower
(1,
1)
Celery
(2,
1)
Cherries
(5,
1)
Corn,
Field
(1.
5,
2,
14)
Cucumbers
(1,
1)
Grapefruit
(12.8,
1)
Grapes
(2.
5,
1)
Lemons
(8,
1)
Lettuce
(1,
1)
Oranges
(15,
1)
<0.07
<0.19
<0.15
<0.19
<0.19
<0.06
<0.08
<0.10
<0.02
<0.06
<0.04
<0.05
<0.10
<0.24
<0.13
<0.05
<0.61
<0.12
<0.38
<0.05
<0.72
1.2
3.2
2.6
3.2
3.2
1.0
1.3
1.6
0.4
1.0
0.6
0.8
1.6
4.0
2.1
0.8
10.2
2.0
6.4
0.8
12.0
Peaches
(5,1)
Peanuts
(2,
1)
Pears
(2,
1)
Pecans
(3,
2,
7)
Peppers
(2,
1)
Pistachios
(5,
1)
Plums
(4,
1)
Potatoes
(1.
5,
1)
Pumpkins
(1.
5,
1)
Rice
(1.
3,
1)
Sorghum
(0.
5,
1)
Squash
(1.
2,
1)
Sugar
Beets
(1.
2,
1)
Sunflower
(1,
1)
Strawberries
(2,
1)
Sweet
Corn
(1.
5,
2,
3)
Tobacco
(2,
1)
Tomatoes
(2,
1)
Walnuts
(4,
1)
Watermelons
(2,
1)
Wheat
(1,1)
<0.24
<0.10
<0.10
<0.27
<0.10
<0.24
<0.19
<0.07
<0.07
<0.06
<0.02
<0.06
<0.06
<0.05
<0.10
<0.14
<0.10
<0.10
<0.19
<0.10
<0.05
4.0
1.6
1.6
4.5
1.6
4.0
3.2
1.2
1.2
1.0
0.4
1.0
1.0
0.8
1.6
2.3
1.6
1.6
3.2
1.6
0.8
1
Only
the
highest
RQs
i.
e.
those
based
on
short
grass
EECs
are
included
in
this
table.
Risk
from
Exposure
to
Granular
Products
Birds
may
be
exposed
to
granular
pesticides
by
ingesting
granules
when
foraging
for
food
or
grit.
Birds
may
also
be
exposed
by
other
routes,
such
as
by
walking
on
exposed
granules
or
by
drinking
water
contaminated
with
granules.
The
number
of
lethal
doses
(LD50)
that
are
available
within
one
square
foot
immediately
after
application
(LD50/
ft2)
is
used
as
the
risk
quotient
for
granular/
bait
products.
Risk
quotients
are
calculated
for
birds
in
three
separate
weight
classes:
1000
g
(e.
g.
waterfowl),
180
g
(e.
g.
upland
gamebirds),
and
20
g
(e.
g.,
songbirds).
Based
on
a
rock
dove
LD50
of
1,000
mg/
kg
and
a
mallard
LD50
greater
than
2,000
mg/
kg,
technical
carbaryl
can
be
classified
as
slightly
to
practically
nontoxic
to
birds
on
an
acute
basis.
LD50
values
for
carbaryl
as
low
as
16.2
mg/
kg
and
56.2
mg/
kg
have
been
reported
for
the
starling
and
the
red
winged
blackbird,
respectively
(Schafer
et
al.,
1983).
Although
these
data
are
based
on
simple
screening
tests,
and
are
therefore
not
reliable
for
risk
assessment
purposes,
they
do
suggest
that
passerine
birds
may
be
significantly
more
sensitive
to
carbaryl
exposure
than
non
passerine
birds.
The
registrant
is
strongly
encouraged
to
submit
acute
oral
toxicity
tests
with
passerine
avian
species.
151
The
acute
RQs
for
granular
carbaryl
are
based
on
a
rock
dove
LD50
of
1,000
(Table
6).
The
avian
acute,
restricted
use,
and
endangered
species
LOCs
are
exceeded
for
birds
in
the
20
g
weight
class,
for
all
granular
carbaryl
uses.
Although
for
most
uses
the
acute
LOC
is
not
exceeded
for
birds
in
the
two
higher
weight
classes,
for
the
trees/
ornamentals,
turfgrass,
and
tick
control
uses
the
avian
acute
risk
LOC
is
also
exceeded
for
birds
in
the
180
g
weight
class.
No
acute
LOCs
are
exceeded
for
birds
in
the
1000
g
weight
class
for
any
of
the
granular
carbaryl
uses.
Table
6.
Avian
acute
risk
quotients
for
granular
carbaryl
(broadcast,
unincorporated)
based
on
LD50
for
rock
dove
(1,000
mg/
kg)
Uses
Rate
in
lb
ai/
A
LD50
(mg/
kg)
Body
Weight
(g)
Acute
RQ
1
(LD50/
ft
2
)
Asparagus,
Brassica
crops
(broccoli,
Brussels
sprouts,
cabbage,
cauliflower,
collards,
etc.),
corn
(field,
sweet),
sorghum,
Solanaceous
crops
(tomato,
pepper,
eggplant),
Leafy
vegetables
(celery,
endive,
lettuce,
parsley,
spinach,
etc.),
Roots
and
tubers
(garden
beets,
carrots,
radishes,
potatoes,
etc.),
strawberries
2
1000
1000
1000
20
180
1000
1.04
0.16
0.02
Cucurbits
(cucumber,
melon,
pumpkin,
squash)
1
1000
1000
1000
20
180
1000
0.52
0.06
0.01
Legumes
(
beans,
peas,
lentils,
cowpeas,
southern
peas)
,
wheat,
millet,
sugar
beets
1.5
1000
1000
1000
20
180
1000
0.78
0.09
0.02
Trees
and
ornamentals,
turfgrass,
tick
control
9.
15
1000
1000
1000
20
180
1000
4.76
0.53
0.10
1
RQ
=
App.
Rate
(lb
ai/
a)
*
(453,590
mg/
lb/
43,560
ft
2
/a)
LD50
mg/
kg
*
Weight
of
Animal
(kg)
Mammalian
acute
and
chronic
risk
Estimating
the
potential
for
adverse
effects
to
wild
mammals
is
based
upon
EFED's
draft
1995
SOP
of
mammalian
risk
assessments
and
methods
used
by
Hoerger
and
Kenaga
(1972)
as
modified
by
Fletcher
et
al.
(1994).
The
concentration
of
carbaryl
in
the
diet
that
is
expected
to
be
acutely
lethal
to
50%
of
the
test
population
(LC50
)
is
determined
by
dividing
the
LD50
value
(usually
rat
LD50)
by
the
%
(decimal
of)
body
weight
consumed.
A
risk
quotient
is
then
determined
by
dividing
the
EEC
by
the
derived
LC50
value.
Risk
quotients
are
calculated
for
three
separate
weight
classes
of
mammals
(15,
35,
and
1000
g),
each
presumed
to
consume
four
different
kinds
of
food
(grass,
forage,
insects,
and
seeds).
The
acute
risk
quotients
for
broadcast
applications
of
nongranular
products
are
tabulated
below.
Risk
from
Exposure
to
Nongranular
Products
Short
grass
152
The
mammalian
acute
risk
LOC
is
exceeded
for
all
registered
nongranular
carbaryl
uses,
at
maximum
label
application
rates,
for
short
grass
feeders
with
a
daily
food
consumption
equal
to
95%
and
66%
of
their
body
weight,
with
RQ
values
ranging
from
0.76
to
12.12
and
from
0.53
to
8.42,
respectively
(Table
7).
The
acute
risk
LOC
for
herbivores
consuming
daily
15%
of
their
body
weight
are
exceeded
for
all
uses
(RQs:
0.56
1.91),
except
for
the
rice,
sugar
beets,
wheat,
millet,
flax,
pasture,
grasses,
noncropland,
alfalfa,
clover,
and
rangeland
use
site
scenarios.
Broadleaf/
forage
plans
and
small
insects
The
acute
risk
LOC
is
exceeded
for
all
nongranular
carbaryl
uses
for
small
mammals
feeding
on
broadleaf/
forage
plants
and
small
insects,
with
RQs
in
the
0.80
6.82
range
for
mammals
with
a
daily
food
consumption
equal
to
95%
of
their
body
weights.
It
is
also
exceeded
for
all
uses,
except
rangeland,
for
mammals
consuming
66%
of
their
body
weights
(RQs:
0.55
to
4.74).
For
mammals
consuming
15
%
of
their
body
weight,
the
acute
risk
LOC
is
reached
or
exceeded
for
citrus,
olives,
pome
fruits,
stone
fruits,
tree
nuts,
sweet
corn,
asparagus,
small
fruits,
berries,
and
turfgrass
(RQs:
0.52
1.08).
RQs
equal
or
exceed
the
acute
restricted
use
or
the
endangered
species
LOCs
for
most
other
uses.
Fruit,
pods,
seeds,
and
large
insects
For
small
mammals
consuming
95%
of
these
food
items,
the
acute
risk
LOC
is
exceeded
for
citrus,
olives,
tree
nuts,
sweet
corn,
and
turfgrass
(RQs:
0.62
0.76).
For
mammals
consuming
66%
of
their
body
weight
the
acute
risk
LOC
is
exceeded
only
for
citrus
in
California
(RQ:
0.53).
For
mammals
that
consume
15%
of
their
body
weight,
the
acute
risk
LOC
is
not
exceeded
for
any
use.
153
Table
7.
Mammalian
(herbivore/
insectivore)
acute
risk
quotients
for
multiple
applications
of
nongranular
carbaryl
(broadcast)
based
on
a
rat
LD50
of
301
mg/
kg
and
maximum
label
use
rates.
Uses,
Application
Rate,
No.
Applications,
Interval
Body
Weight
(g)
%
Body
Weight
Con_
sumed
LC50
(LD50/%
Body
Wt
Con_
sumed
EEC:
Short
Grass
(ppm)
EEC:
Forage
&
Small
Insects
(ppm)
EEC:
Fruit,
Seeds,
Lg
Insects
(ppm)
Acute
RQ:
Short
Grass
Acute
RQ:
Forage
&
Small
Insects
Acute
RQ:
Large
Insects
Citrus,
5
lb
ai/
A,
4
appl,
14
days
15
35
1000
95
66
15
316.84
456.06
2006.67
3320.98
3320.98
3320.98
1868.05
1868.05
1868.05
207.56
207.56
207.56
10.48
7.28
1.65
5.90
4.10
0.93
0.66
0.46
0.10
Citrus
(California),
16
lb
ai/
A,
1
appl
15
35
1000
95
66
15
316.84
456.06
2006.67
3840.00
3840.00
3840.00
2160.00
2160.00
2160.00
240.00
240.00
240.00
12.12
8.42
1.91
6.82
4.74
1.08
0.76
0.53
0.12
Olives,
7.5
lb
ai/
A
2
appl,
14
days
15
35
1000
95
66
15
316.84
456.06
2006.67
3164.15
3164.15
3164.15
1779.83
1779.83
1779.83
197.76
197.76
197.76
9.99
6.94
1.58
5.62
3.90
0.89
0.62
0.43
0.10
Pome
fruits
(apples,
etc.),
3
lb
ai/
A,
5
appl,
14
days
15
35
1000
95
66
15
316.84
456.06
2006.67
2230.10
2230.10
2230.10
1254.43
1254.43
1254.43
139.38
139.38
139.38
7.04
4.89
1.11
3.96
2.75
0.63
0.44
0.31
0.07
Stone
fruits
(peaches,
etc.),
4
lb
ai/
A,
3
appl,
14
days
15
35
1000
95
66
15
316.84
456.06
2006.67
2238.92
2238.92
2238.92
1259.39
1259.39
1259.39
139.93
139.93
139.93
7.07
4.91
1.12
3.97
2.76
0.63
0.44
0.31
0.07
Tree
nuts
(pistachios,
etc.),
5
lb
ai/
A,
3
appl,
7
days
15
35
1000
95
66
15
316.84
456.06
2006.67
3154.09
3154.09
3154.09
1774.18
1774.18
1774.18
197.13
197.13
197.13
9.95
6.92
1.57
5.60
3.89
0.88
0.62
0.43
0.10
Corn,
field,
2
lb
ai/
A
4
appl,
14
days
15
35
1000
95
66
15
316.84
456.06
2006.67
1328.39
1328.39
1328.39
747.22
747.22
747.22
83.02
83.02
83.02
4.19
2.91
0.66
2.36
1.64
0.37
0.26
0.18
0.04
Corn,
sweet,
2
lb
ai/
A
8
appl,
3
days
15
35
1000
95
66
15
316.84
456.06
2006.67
3148.03
3148.03
3148.03
1770.77
1770.77
1770.77
196.75
196.75
196.75
9.94
6.90
1.57
5.59
3.88
0.88
0.62
0.43
0.10
Rice
(tadpole
shrimp),
sunflower,
1.5
lb
ai/
A,
2
appl,
7
days
15
35
1000
95
66
15
316.84
456.06
2006.67
673.40
673.40
673.40
378.79
378.79
378.79
42.09
42.09
42.09
2.13
1.48
0.34
1.20
0.83
0.19
0.13
0.09
0.02
Sugar
beets,
wheat,
millet,
flax,
pasture,
grasses,
noncropland
1.5
lb
ai/
A,
2
appl,
14
days
15
35
1000
95
66
15
316.84
456.06
2006.67
632.83
632.83
632.83
355.97
355.97
355.97
39.55
39.55
39.55
2.00
1.39
0.32
1.12
0.78
0.18
0.12
0.09
0.02
Asparagus,
2
lb
ai/
A,
5
appl,
3
days
15
35
1000
95
66
15
316.84
456.06
2006.67
2138.64
2138.64
2138.64
1202.99
1202.99
1202.99
133.67
133.67
133.67
6.75
4.69
1.07
3.80
2.64
0.60
0.42
0.29
0.07
Cucurbits
(cucumbers
melons,
squash,
etc.),
trees
&
ornamentals,
1
lb
ai/
A,
6
appl,
7
days
15
35
1000
95
66
15
316.84
456.06
2006.67
1047.00
1047.00
1047.00
588.94
588.94
588.94
65.44
65.44
65.44
3.30
2.30
0.56
1.86
1.29
0.29
0.21
0.14
0.03
154
Solanaceous
(peppers,
tomatoes,
eggplant),
sweet
potatoes,
peanuts,
tobacco,
2
lb
ai/
A,
4
appl,
7
days
15
35
1000
95
66
15
316.84
456.06
2006.67
1578.32
1578.32
1578.32
887.80
887.80
887.80
98.64
98.64
98.64
4.98
3.46
0.79
2.80
1.95
0.44
0.31
0.22
0.05
Table
7.
Mammalian
(herbivore/
insectivore)
acute
risk
quotients
for
multiple
applications
of
nongranular
carbaryl
(broadcast)
based
on
a
rat
LD50
of
301
mg/
kg
and
maximum
label
use
rates.
Uses,
Application
Rate,
No.
Applications,
Interval
Body
Weight
(g)
%
Body
Weight
Con_
sumed
LC50
(LD50/%
Body
Wt
Con_
sumed
EEC:
Short
Grass
(ppm)
EEC:
Forage
&
Small
Insects
(ppm)
EEC:
Fruit,
Seeds,
Lg
Insects
(ppm)
Acute
RQ:
Short
Grass
Acute
RQ:
Forage
&
Small
Insects
Acute
RQ:
Large
Insects
Leafy
veg
(celery,
lettuce,
etc.),
Brassica
(broccoli,
cabbage,
etc.),
roots
&
tubers
(carrots,
potatoes,
etc.),
sorghum,
2
lb
ai/
A,
3
appl,
7
days
15
35
1000
95
66
15
316.84
456.06
2006.67
1261.64
1261.64
1261.64
709.67
709.67
709.67
78.85
78.85
78.85
3.98
2.77
0.63
2.24
1.56
0.35
0.25
0.17
0.04
Legumes
(beans,
peas,
lentils,
cowpeas),
1.5
lb
ai/
A,
4
appl,
7
days
15
35
1000
95
66
15
316.84
456.06
2006.67
1183.74
1183.74
1183.74
665.85
665.85
665.85
73.98
73.98
73.98
3.74
2.60
0.59
2.10
1.46
0.33
0.23
0.16
0.04
Small
fruits
&
berries
(grapes,
strawberries,
etc.),
2
lb
ai/
A,
5
appl
7
days
15
35
1000
95
66
15
316.84
456.06
2006.67
1854.01
1854.01
1854.01
1042.88
1042.88
1042.88
115.88
115.88
115.88
5.85
4.07
0.92
3.29
2.29
0.52
0.37
0.25
0.06
Alfalfa,
clover,
1.5
lb
ai/
A,
10
appl,
30
days
15
35
1000
95
66
15
316.84
456.06
2006.67
796.72
796.72
796.72
448.15
448.15
448.15
49.79
49.79
49.79
2.53
1.76
0.40
1.42
0.99
0.22
0.16
0.11
0.02
Rangeland,
1
lb
ai/
A,
1
appl
15
35
1000
95
66
15
316.84
456.06
2006.67
240.00
240.00
240.00
135.00
135.00
135.00
15.00
15.00
15.00
0.76
0.53
0.12
0.43
0.30
0.07
0.05
0.03
0.01
Forested
areas
non
urban),
1
lb
ai/
A,
2
appl,
7
days
15
35
1000
95
66
15
316.84
456.06
2006.67
448.93
448.93
448.93
252.52
252.52
252.52
28.06
28.06
28.06
1.42
0.98
0.22
0.80
0.55
0.13
0.09
0.06
0.01
Turfgrass,
8
lb
ai/
A,
2
appl,
7
days
15
35
1000
95
66
15
316.84
456.06
2006.67
3591.46
3591.46
3591.46
2020.19
2020.19
2020.19
224.47
224.47
224.47
11.34
7.87
1.79
6.38
4.43
1.01
0.71
0.49
0.11
Although
neither
the
acute
risk
nor
the
acute
restricted
use
LOC
is
exceeded
for
granivores
for
any
of
the
nongranular
carbaryl
uses,
the
acute
endangered
species
LOC
is
reached
or
exceeded
for
citrus,
olives,
pome
and
stone
fruits,
tree
nuts,
sweet
corn,
and
turfgrass
(RQs:
0.10
0.16),
and
for
citrus,
olives,
tree
nuts,
sweet
corn,
and
turfgrass
(RQs:
0.10
0.12),
for
granivores
with
daily
food
consumption
equal
to
21%
and
15%
of
their
body
weight,
respectively
(Table
8).
No
acute
LOCs
are
exceeded
for
granivores
which
consume
daily
3%
of
their
body
weight.
155
Table
8.
Mammalian
(granivore)
acute
risk
quotients
for
multiple
applications
of
nongranular
carbaryl
(broadcast)
based
on
a
rat
LD50
of
301
mg/
kg
and
maximum
label
use
rates.
Uses,
Application
Rate,
No.
Applications,
Interval
Body
Weight
(g)
%
Body
Weight
Consumed
LC50
(LD50
÷
%
Body
Weight
Consumed)
EEC:
Seeds
(ppm)
Acute
RQ:
Seeds
Citrus,
5
lb
ai/
A,
4
appl,
14
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
207.56
207.56
207.56
0.14
0.10
0.02
Citrus
(California),
16
lb
ai/
A,
1
appl
15
35
1000
21
15
3
1433.33
2000.67
10033.33
240.00
240.00
240.00
0.16
0.12
0.00
Olives,
7.5
lb
ai/
A,
2
appl,
14
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
197.76
197.76
197.76
0.14
0.10
0.02
Pome
fruits
(apple,
pear,
etc.),
3
lb
ai/
A,
3
appl,
14
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
139.38
139.38
139.38
0.10
0.07
0.01
Stone
fruits
(peach,
apricot,
etc.),
4
lb
ai/
A,
3
appl,
14
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
139.93
139.93
139.93
0.10
0.07
0.01
Tree
nuts
(pistachios,
etc.),
5
lb
ai/
A,
3
appl,
7
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
197.13
197.13
197.13
0.13
0.10
0.02
Corn,
field,
2
lb
ai/
A,
4
appl,
14
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
83.02
83.02
83.02
0.06
0.04
0.02
Corn,
sweet,
2
lb
ai/
A,
8
appl,
3
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
196.75
196.75
196.75
0.13
0.10
0.00
Rice,
sunflower,
1.5
lb
ai/
A,
2
appl,
7
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
42.09
42.09
42.09
0.03
0.02
0.00
Sugar
beets,
wheat
&
millet,
flax,
pasture,
grasses,
noncropland,
1.5
lb
ai/
A,
2
appl,
14
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
39.55
39.55
39.55
0.03
0.02
0.00
Asparagus,
4
lb
ai/
A,
2
appl,
7
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
133.67
133.67
133.67
0.09
0.07
0.01
Brassica
crops
(broccoli,
cabbage,
etc.),
leafy
veg
(celery,
lettuce,
etc.),
Roots
&
tubers
(beets,
carrot,
potato,
etc.),
sorghum,
2
lb
ai/
A,
3
appl,
7
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
78.85
78.85
78.85
0.05
0.04
0.01
Cucurbits
(cucumbers,
melons,
squash,
etc.),
trees
and
ornamentals,
1
lb
ai/
A,
6
appl,
7
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
65.44
65.44
65.44
0.04
0.03
0.01
Solanaceous
(pepper,
tomato,
eggplant),
sweet
potato,
peanuts,
tobacco,
2
lb
ai/
A,
4
appl,
7
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
98.64
98.64
98.64
0.07
0.05
0.01
156
Legumes
(beans,
peas,
lentils,
cowpeas),
1.5
lb
ai/
A,
4
appl,
7
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
73.98
73.98
73.98
0.05
0.04
0.01
Table
8.
Mammalian
(granivore)
acute
risk
quotients
for
multiple
applications
of
nongranular
carbaryl
(broadcast)
based
on
a
rat
LD50
of
301
mg/
kg
and
maximum
label
use
rates.
Uses,
Application
Rate,
No.
Applications,
Interval
Body
Weight
(g)
%
Body
Weight
Consumed
LC50
(LD50
÷
%
Body
Weight
Consumed)
EEC:
Seeds
(ppm)
Acute
RQ:
Seeds
Small
fruits
&
berries
(grapes,
strawberries,
etc.),
2
lb
ai/
A,
5
appl
7
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
115.88
115.88
115.88
0.08
0.06
0.01
Alfalfa,
clover,
1.5
lb
ai/
A,
10
appl,
30
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
49.79
49.79
49.79
0.03
0.02
0.00
Rangeland,
1
lb
ai/
A,
1
appl
15
35
1000
21
15
3
1433.33
2000.67
10033.33
15.00
15.00
15.00
0.01
0.01
0.00
Forested
areas
(non
urban),
1
lb
ai/
A,
2
appl,
7
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
28.06
28.06
28.06
0.02
0.01
0.00
Turfgrass,
8
lb
ai/
A,
2
appl,
7
days
15
35
1000
21
15
3
1433.33
2000.67
10033.33
224.47
224.47
224.47
0.15
0.11
0.02
Assummarized
inTable9,at
maximumlabelapplicationrates,
themammalianchronicLOC
(1)
is
exceeded
for
all
registered
uses
of
nongranular
carbaryl
for
all
food
item
groups,
with
chronic
RQ
values
in
the
range
of:
3.0
48.0
(for
short
grasses),
1.4
22.0
(for
tall
grasses),
and
1.7
27.0
(for
broadleaf/
forage
plants,
small
insects).
The
mammalian
chronic
LOC
is
exceeded
for
the
fruits/
pods/
seeds/
large
insects
food
items
for
the
following
uses:
citrus,
olives,
pome
and
stone
fruits,
tree
nuts,
field
and
sweet
corn,
asparagus,
solanaceous
vegetable
crops,
sweet
potatoes,
peanuts,
tobacco,
small
fruits
and
berries,
and
turfgrass
(chronic
RQs
=
1.0
3.0).
157
Table
9.
Mammalian
chronic
risk
quotients
for
multiple
applications
of
nongranular
carbaryl
(broadcast)
based
on
a
developmental
rat
NOAEC
of
80
ppm
and
maximum
label
application
rates
Site,
Application
Rate,
Number
of
Applications,
Interval
Food
Items
Peak
Mean
EEC
(ppm)
Chronic
RQ
(EEC)/
NOAEC)
Citrus,
5
lb
ai/
A,
4
appl,
14
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
3320.98
1522.12
1868.05
207.56
41.51
19.03
23.35
2.59
Citrus
(California),
16
lb
ai/
A,
1
appl
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
3840.00
1760.00
2160.00
240.00
48.00
22.00
27.00
3.00
Olives,
7.5
lb
ai/
A,
2
appl,
14
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
3164.15
1450.23
1779.83
197.76
39.55
18.13
22.25
2.47
Pome
fruits
(apples,
etc.),
3
lb
ai/
A,
5
appl,
14
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
2230.10
1022.13
1254.43
139.38
27.88
12.78
15.68
1.74
Stone
fruits
(peaches,
etc.),
4
lb
ai/
A,
3
appl,
14
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
2238.92
1026.17
1259.39
139.93
27.99
12.83
15.74
1.75
Tree
nuts
(pistachios,
etc.),
5
lb
ai/
A,
3
appl,
7
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
3154.09
1445.62
1774.18
197.13
39.43
18.07
22.18
2.46
Corn,
field,
2
lb
ai/
A,
4
appl,
14
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
1328.39
608.85
747.22
83.02
16.60
7.61
9.34
1.04
Corn,
sweet,
2
lb
ai/
A,
8
appl,
3
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
3148.03
1442.85
1770.77
196.75
39.35
18.04
22.13
2.46
Rice,
sunflower,
1.5
lb
ai/
A,
2
appl,
7
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
673.40
308.64
378.79
42.09
8.42
3.86
4.73
0.53
Asparagus,
2
lb
ai/
A,
5
appl,
3
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
2138.64
980.21
1202.99
133.67
26.73
12.25
15.04
1.67
Brassica
crops
(broccoli,
cabbage,
etc.),
leafy
veg
(celery,
lettuce,
etc.),
roots
&
tubers
(beets,
carrots,
potatoes,
etc.),
sorghum,
2
lb
ai/
A,
3
appl,
7
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
1261.64
578.25
709.67
78.85
15.77
7.23
8.87
0.99
158
Table
9.
Mammalian
chronic
risk
quotients
for
multiple
applications
of
nongranular
carbaryl
(broadcast)
based
on
a
developmental
rat
NOAEC
of
80
ppm
and
maximum
label
application
rates
Site,
Application
Rate,
Number
of
Applications,
Interval
Food
Items
Peak
Mean
EEC
(ppm)
Chronic
RQ
(EEC)/
NOAEC)
Cucurbits
(cucumbers
melons,
squash,
etc.),
trees
and
ornamentals,
1
lb
ai/
A,
6
appl,
7
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
1047.00
479.88
588.94
65.44
13.09
6.00
7.36
0.82
Solanaceous
(peppers,
tomatoes,
eggplant),
sweet
potatoes,
peanuts,
tobacco,
2
lb
ai/
A,
4
appl,
7
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
1578.32
723.40
887.80
98.64
19.73
9.04
11.10
1.23
Legumes
(beans,
peas,
lentils,
cowpeas),
1.5
lb
ai/
A,
4
appl,
7
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
1183.74
542.55
665.85
73.98
14.80
6.78
8.32
0.92
Sugar
beets,
wheat,
millet,
flax,
pasture,
grasses,
noncropland
1.5
lb
ai/
A,
2
appl,
14
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
632.83
290.05
355.97
39.55
7.91
3.63
4.45
0.49
Small
fruits
&
berries
(grapes,
strawberries,
etc.),
2
lb
ai/
A,
5
appl,
7
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
1854.01
849.75
1042.88
115.88
23.18
10.62
13.04
1.45
Alfalfa,
clover,
1.5
lb
ai/
A,
8
appl,
30
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
796.72
365.16
448.15
49.79
9.96
4.56
5.60
0.62
Rangeland,
1
lb
ai/
A,
1
appl
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
240.00
110.00
135.00
15.00
3.00
1.38
1.69
0.19
Forested
areas
(non
urban),
1
lb
ai/
A,
2
appl,
7
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
448.93
205.76
252.52
28.06
5.61
2.57
3.16
0.35
Turfgrass,
8
lb
ai/
A,
2
appl,
7
days
Short
Grass
Tall
Grass
Broad
Leaf
Seed
Fruit
3591.46
1646.08
2020.19
224.47
44.89
20.58
25.25
2.81
In
addition
to
maximum
label
use
rates,
mammalian
acute
and
chronic
RQs
were
also
calculated
for
nongranular
carbaryl
using
QUA
average
use
rates
data
available
for
for
70
uses
(Table
10a)
and
maximum
reported
(Doane
data)
use
rates
data
available
for
42
uses
(Table
10b).
As
summarized
in
Table
10a,
when
RQs
are
based
on
QUA
average
rates,
the
acute
risk
LOC
is
exceeded
for
63
uses,
whereas
the
restricted
use
LOC
is
exceeded
for
69
uses
(not
exceeded
only
159
for
Chinese
cabbage),
and
the
endangered
species
LOC
is
exceeded
for
all
70
uses.
The
chronic
risk
LOC
is
exceeded
for
69
uses
(not
exceeded
only
for
Chinese
cabbage).
Table
10a.
Mammalian
(herbivores)
highest
acute
and
chronic
risk
quotients
1
for
nongranular
carbaryl
based
on
a
rat
LD50
of
301
mg/
kg
ppm,
a
developmental
rat
NOAEC
of
80
ppm,
and
QUA
average
application
rates
for
70
uses
Use
site
Acute
RQ
(EEC/
LC50)
Chronic
RQ
(EEC/
NOAEC)
Use
Site
Acute
RQ
(EEC/
LC50)
Chronic
RQ
(EEC/
NOAEC)
Alfalfa
Almonds
Apples
Asparagus
Beans,
Dry
Beans,
Lima,
Fresh
Beans,
Snap,
Fresh
Beans,
Snap,
Processed
Beets
Blackberries
Blueberries
Broccoli
Brussels
Sprouts
Chinese
Cabbage
Fresh
Cabbage
Cantaloupes
Carrots
Cauliflower
Celery
Cherries
Citrus,
other
Corn,
Field
Cranberries
Cucumbers
Cucumbers,
Processed
Eggplant
Flax
Grapefruit
Grapes
Hay
Hazelnuts
Lemons
Lettuce
Lots/
Farmsteads
Melons
0.84
1.59
0.91
0.68
0.38
0.68
1.28
0.99
0.38
1.28
1.28
0.60
0.68
0.15
1.42
0.60
1.28
0.84
1.42
1.44
2.40
0.75
1.52
0.84
0.85
1.42
0.84
1.87
1.98
0.60
1.90
2.05
0.84
0.70
0.53
3.30
6.30
4.11
2.70
1.50
2.70
5.05
3.93
1.50
5.10
5.10
2.40
2.70
0.60
5.61
2.40
5.05
3.30
5.61
5.70
9.49
3.00
6.00
3.30
3.37
5.61
3.30
7.38
7.86
2.40
7.50
8.10
3.30
2.80
2.10
Nectarines
Okra
Olives
Oranges
Pasture
Peaches
Peanuts
Pears
Pears,
Dry
Peas,
Green
Pecans
Peppers,
Bell
Peppers,
Sweet
Pistachios
Plums
Potatoes
Pumpkins
Raspberries
Rice
Sorghum
Soybeans
Squash
Strawberries
Sugar
Beets
Sunflower
Sweet
Corn,
Fresh
Sweet
Potatoes
Tobacco
Tomatoes,
Fresh
Tomatoes,
Processed
Walnuts
Watermelons
Wheat,
Spring
Wheat,
Winter
Woodland
2.88
1.44
4.02
2.58
0.68
1.99
0.60
1.34
0.75
1.13
1.98
1.28
0.99
2.72
2.88
1.13
2.84
2.12
0.84
0.84
0.68
1.06
1.98
0.99
0.31
2.78
1.21
1.42
1.40
0.91
1.44
0.38
0.46
0.60
0.31
11.40
5.70
15.90
10.20
2.70
7.89
2.40
5.27
3.00
4.50
7.86
5.05
3.90
10.80
11.40
4.49
11.22
8.40
3.30
3.30
2.70
4.20
7.86
3.90
2.10
11.04
4.80
5.61
5.52
3.60
5.70
1.50
1.80
2.40
2.10
1
Only
the
highest
RQs
i.
e.
those
corresponding
to
15
g
mammals
which
have
a
daily
food
consumption
equal
to
95%
of
their
body
weight
and
based
on
short
grass
EECs
are
included
in
this
table.
When
RQs
are
calculated
using
maximum
reported
application
rates,
the
acute
risk
LOC
is
exceeded
for
41
of
the
42
uses
(RQs:
0.60
11.36).
The
restricted
use,
endangered
species,
and
chronic
(RQs:
1.5
45)
risk
LOCs
are
exceeded
for
all
42
uses
(Table
10b).
160
Table
10b
Mammalian
(herbivores)
highest
acute
and
chronic
risk
quotients
1
for
nongranular
carbaryl
based
on
a
rat
LD50
of
301
mg/
kg
ppm
and,
a
developmental
rat
NOAEC
of
80
ppm,
and
maximum
reported
use
rates
(Doane
data)
for
42
uses
Use
site
[appl.
rate
(lb
ai/
A),
No.
appl]
Acute
RQ
(EEC/
LC50)
Chronic
RQ
(EEC/
NOAEC)
Use
Site
[appl.
rate
(lb
ai/
A)
No.
appl]
Acute
RQ
(EEC/
LC50)
Chronic
RQ
(EEC/
NOAEC)
Alfalfa
(1.
5,
1)
Almonds
(4,
1)
Apples
(3.
2,
1)
Apricots
(4,
1)
Asparagus
(4,
1)
Beans,
Lima
(1.
3,
1)
Beans,
snap
(1.
6,
1)
Cabbage
(2,
1)
Canola
(0.
5,
1)
Cantaloupe
(1.
2,
1)
Carrots
(0.
8,
1)
Cauliflower
(1,
1)
Celery
(2,
1)
Cherries
(5,
1)
Corn,
Field
(1.
5,
2,
14)
Cucumbers
(1,
1)
Grapefruit
(12.8,
1)
Grapes
(2.
5,
1)
Lemons
(8,
1)
Lettuce
(1,
1)
Oranges
(15,
1)
1.13
3.03
2.43
3.03
3.03
0.99
1.21
1.52
0.38
0.91
0.60
0.75
1.53
3.78
2.00
0.75
9.70
1.90
6.06
0.75
11.36
4.5
12.0
9.62
12.0
12.0
3.9
4.8
6.0
1.5
3.6
2.4
3.0
6.0
15.0
7.9
3.0
38.4
7.5
24.0
3.0
45.0
Peaches
(5,
1)
Peanuts
(2,
1)
Pears
(2,
1)
Pecans
(3,
2,
7)
Peppers
(2,
1)
Pistachios
(5,
1)
Plums
(4,
1)
Potatoes
(1.
5,
1)
Pumpkins
(1.
5,
1)
Rice
(1.
3,
1)
Sorghum
(0.
5,
1)
Squash
(1.
2,
1)
Sugar
Beets
(1.
2,
1)
Sunflower
(1,
1)
Strawberries
(2,
1)
Sweet
Corn
(1.
5,
2,
3)
Tobacco
(2,
1)
Tomatoes
(2,
1)
Walnuts
(4,
1)
Watermelons
(2,
1)
Wheat
(1,1)
3.78
1.52
1.52
4.25
1.52
3.78
3.03
1.13
1.13
0.99
0.38
0.91
0.91
0.75
1.52
2.20
1.52
1.52
3.03
1.52
0.75
15.0
6.0
6.0
16.8
6.0
15.0
12.0
4.5
4.5
3.9
1.5
3.6
3.6
3.0
6.0
8.7
6.0
6.0
12.0
6.0
3.0
1
Only
the
highest
RQs
i.
e.
those
corresponding
to
15
g
mammals
which
have
a
daily
food
consumption
equal
to
95%
of
their
body
weight
and
based
on
short
grass
EECs
are
included
in
this
table.
Risk
to
Granular
Products
Mammals
also
may
be
exposed
to
granular/
bait
pesticides
through
ingestion
and
by
other
routes,
such
as
by
walking
on
exposed
granules
or
by
drinking
water
contaminated
with
granules.
The
number
of
lethal
doses
(LD50)
that
are
available
within
one
square
foot
immediately
after
application
(LD50/
ft2)
is
used
as
the
risk
quotient
for
granular/
bait
products.
Risk
quotients
are
calculated
for
small
mammals
in
three
weight
classes:
15
g,
35
g,
and
1000
g.
The
acute
level
of
concern
is
exceeded
for
mammals
in
the
15
g
and
35
g
categories
for
all
40
registered
granular
uses
(Table
11).
For
1000
g
mammals,
the
restricted
use
and
endangered
species
LOCs
are
exceeded
for
applications
to
trees
and
ornamentals,
turfgrass,
and
tick
control.
161
Table
11.
Mammalian
acute
risk
quotients
for
granular
carbaryl
(broadcast,
unincorporated)
based
on
a
rat
LD50
of
301
mg/
kg
Uses
Rate
in
lb
ai/
A
Body
Weight
(g)
Acute
RQ
1
(LD50/
ft
2
)
Asparagus,
Brassica
crops
(broccoli,
cabbage,
cauliflower,
collards,
etc.),
corn
(field,
sweet),
sorghum,
solanaceous
crops
(tomato,
pepper,
eggplant),
leafy
vegetables
(celery,
lettuce,
parsley,
spinach,
etc.),
roots
&
tubers
(beets,
carrots,
radishes,
potatoes,
etc.),
strawberries
2
15
35
1000
4.61
1.98
0.07
Cucurbits
(cucumber,
melon,
pumpkin,
squash)
1
15
35
1000
2.30
0.99
0.03
Legumes
(
beans,
peas,
lentils,
cowpeas,
southern
peas),
Wheat,
millet,
Sugar
beets
1.5
15
35
1000
3.45
1.48
0.05
Trees
and
ornamentals,
turfgrass,
tick
control
9.
15
15
35
1000
21.10
9.04
0.32
1
RQ
=
Appl.
rate
(lb
ai/
a)
*
(453,590
mg/
lb/
43,560
ft
2
/a)
LD50
mg/
kg
*
weight
of
animal
(kg)
Insects
Currently
EFED
does
not
assess
risk
to
nontarget
insects.
However,
data
from
acceptable
studies
are
used
to
recommend
appropriate
label
precautions.
Carbaryl,
is
highly
toxic
to
domestic
and
wild
bees
and
should
be
applied
only
under
the
conditions
specified
by
the
latest
pollinator
protection
label
language.
Carbaryl
has
also
been
shown
to
be
from
moderately
to
highly
toxic
to
predaceous
and
parasitic
arthropods,
including
lace
bugs,
big
eyed
bugs,
lady
beetles,
carabid
ground
beetles,
hymenopterous
parasitoids,
predaceous
mites,
and
spiders.
Terrestrial
Plants
There
in
no
data
to
assess
risk
to
terrestrial
plants.
However,
based
on
precautionary
label
language
about
potential
injury
to
several
crop
plants,
the
registrant
needs
to
submit
tier
I
and,
if
necessary,
tier
II
Seed
Germination
and
Seedling
Emergence
and
Vegetative
Vigor
studies.
Exposure
and
Risk
to
Nontarget
Aquatic
Animals
EFED
calculates
estimated
environmental
concentrations
(EECs)
using
the
PRZM/
EXAMS
model.
The
EECs
are
used
for
assessing
acute
and
chronic
risks
to
aquatic
organisms.
Acute
risk
assessments
are
performed
using
peak
EEC
values
for
single
and
multiple
applications.
Chronic
risk
assessments
are
performed
using
the
21
day
EECs
for
invertebrates
and
56
day
EECs
for
fish.
The
PRZM/
EXAMS
program
uses
basic
environmental
fate
data
and
pesticide
label
application
information
to
estimate
the
expected
EECs
following
treatment
of
10
hectares.
The
162
model
calculates
the
concentration
(EEC)
of
a
pesticide
in
a
one
hectare,
two
meter
deep
pond,
taking
into
account
the
following:
(1)
adsorption
to
soil
or
sediment,
(2)
soil
incorporation,
(3)
degradation
in
soil
before
washoff
to
a
water
body,
and
(4)
degradation
within
the
water
body.
The
model
also
accounts
for
direct
deposition
of
spray
drift
into
the
water
body
(assumed
to
be
1%
and
5%
of
the
application
rate
for
ground
and
aerial
applications,
respectively).
The
environmental
fate
parameters
used
in
the
model
for
this
pesticide
are:
soil
KOC
211,
solubility:
32
mg/
L,
aerobic
soil
metabolism
half
life
of
4
days,
hydrolysis:
stable
at
pH
5,
12
days
at
pH
7,
5
hrs
at
Ph9,
water
photolysis21days,
aerobicaquaticmetabolismhalf
life:4.9,
anaerobicaquaticmetabolismhalf
life:
4.9
days.
EECs
are
tabulated
in
Table
12.
Table12.Tier
IIsurfacewaterestimated
environmentalconcentration(EEC)values
derivedfromPRZM/EXAMS
modeling
for
use
in
ecorisk
assessment
(Calculated
using
standard
pond.)
Use
Site,
Application
Method
Number
of
Applications
Per
Year
Application
Rate
(Pounds
A.
I.
per
Application)
Surface
Water
Acute
(ppb)
(1
in
10
year
peak
single
day
concentration)
21
day
(ppb)
(1
in
10
year)
60
day
(ppb)
(1
in
10
year)
Sweet
Corn
(OH),
air/
ground
Maximum
"Average"
Maximum
Reported
8
2
3
2
3.4
1
46
16
14
26
10
8
21
5
4
Field
Corn
(OH),
air/
ground
Maximum
"Average"
Maximum
Reported
4
2
2
2
1
1.5
28
12
18
16
6
9.5
10
3
5
Apples
(OR),
air/
ground
Maximum
"Average"
Maximum
Reported
5
2
2
2
1.2
1.6
8.6
4.5
6.0
4.9
2.5
3
4
1
2
Sugar
Beets
(MN),
air/
ground
Maximum
"Average"
Maximum
Reported
2
1
1
1.5
1.5
1.2
19
14
11
11
7
5
5
3
2
Citrus
(FL),
air/
ground
Maximum
"Average"
Maximum
Reported
4
2
3
5
3.4
4.3
274
145
232
137
67
112
79
33
55
Freshwater
Fish
Acuteand
chronicriskquotientsfor
freshwaterfish,basedon
maximumlabel,QUAaverage,
and
maximum
reported
(Doane
data)
use
rates
are
tabulated
in
Table
13.
The
acute
risk
LOC
is
exceeded
only
for
the
citrus
scenario,
for
all
three
use
rates
modeled,
whereas
the
endangered
species
LOC
is
met
or
exceeded
for
four
scenarios,
for
all
three
use
rates.
The
chronic
risk
LOC
is
is
not
exceeded
for
any
use
scenario,
for
any
use
rates.
163
Table
13.
Risk
quotients
for
freshwater
fish
based
on
an
Atlantic
salmon
LC50
of
250
ppb
and
a
fathead
minnow
NOAEC
of
210
ppb,
at
maximum
label
use
rates,
QUA
average
use
rates,
and
maximum
reported
use
rates
Site/
Appl.
Method
Use
Rates
LC50
(ppb)
NOAEC
(ppb)
EEC
Initial/
Peak
(ppb)
EEC
60
Day
Ave.
(ppb)
Acute
RQ
(EEC/
LC50)
Chronic
RQ
(EEC/
NOAEC)
Sweet
Corn
(OH),
air/
ground
Maximum
"Average"
Max
Rep
250
210
46
16
14
21
5
4
0.18
0.06
0.06
0.10
0.02
0.02
Field
Corn
(OH)
air/
ground
Maximum
"Average"
Max
Rep
250
210
28
12
18
10
3
5
0.11
0.05
0.07
0.05
0.01
0.02
Apples
(OR)
air/
ground
Maximum
"Average"
Max
Rep
250
210
8.6
4.5
6.0
4
1
2
0.03
0.02
0.02
0.02
0.00
0.01
Sugar
Beets
(MN)
air/
ground
Maximum
"Average"
Max
Rep
250
210
19
14
11
5
3
2
0.08
0.06
0.04
0.02
0.01
0.01
Citrus
(FL)
air/
ground
Maximum
"Average"
Max
Rep
250
210
274
145
232
79
33
55
1.10
0.58
0.93
0.38
0.16
0.26
The
risk
quotients
for
freshwater
invertebrates
exceed
both
the
acute
and
chronic
LOCs
for
all
five
use
scenarios
modeled,
at
maximum
label
use
rates,
QUA
average
rates,
and
maximum
reported
(Doane
data)
use
rates
(Table
14).
Table
14.
Risk
quotients
for
freshwater
invertebrates
based
on
a
stonefly
EC50
of
1.7
ppb
and
a
water
flea
NOAEC
of
1.5
ppb
,
at
maximum
label
use
rates,
QUA
average
use
rates,
and
maximum
reported
use
rates
Site/
Appl.
Method
Use
Rates
EC50
(ppb)
NOAEC
(ppb)
EEC
Initial/
Peak
(ppb)
EEC
21
Day
Ave.
(ppb)
Acute
RQ
(EEC/
EC50)
Chronic
RQ
(EEC/
NOAEC)
Sweet
Corn
(OH)
Maximum
"Average"
Max
Rep
1.7
1.5
46
16
14
26
10
8
27.06
9.40
8.20
17.33
6.67
5.33
Field
Corn
(OH)
Maximum
"Average"
Max
Rep
1.7
1.5
28
12
18
16
6
9.5
16.47
7.06
10.59
10.67
4.00
6.33
Apples
(OR)
Maximum
"Average"
Max
Rep
1.7
1.5
8.
6
4.5
6.0
4.9
2.5
3
5.06
2.65
3.30
3.27
1.67
2.00
Sugar
Beets
(MN)
Maximum
"Average"
Max
rep
1.7
1.5
19
14
11
11
7
5
11.18
8.24
6.47
7.33
4.67
3.33
Citrus
(FL)
Maximum
"Average"
Max
Rep
1.7
1.5
274
145
232
137
67
112
161.18
85.29
136.47
91.33
44.67
74.67
164
Estuarine
and
Marine
Animals
The
acute
risk
LOC
is
not
exceeded
for
any
of
the
five
use
scenarios
modeled
using
maximum
label
use
rates,
QUA
average
rates,
and
maximum
reported
rates
(Table
15).
The
acute
endangered
species
LOC
is
exceeded
at
maximum
label
rates
for
the
citrus
scenario.
Due
to
the
unavailability
of
core
chronic
toxicity
data,
it
is
not
possible
to
evaluate
chronic
risk
to
estuarine/
marine
fish
at
this
time.
Table
15.
Acute
risk
quotients
for
estuarine/
marine
fish
based
on
a
sheepshead
minnow
LC50
of
2.6
ppm
and
label
maximum
and
QUA
average
use
rates,
at
maximum
label
use
rates,
QUA
average
use
rates,
and
maximum
reported
use
rates
Site/
Appl.
Method
Use
Rates
LC50
(ppb)
EEC
Initial/
Peak
(ppb)
(Max
Rates)
Acute
RQ
(EEC/
EC50)
Sweet
Corn
(OH)
Maximum
"Average"
Max
Rep
2600
46
16
14
0.02
0.01
0.00
Field
Corn
(OH)
Maximum
"Average"
Max
Rep
2600
28
12
18
0.01
0.00
0.01
Apples
(OR)
Maximum
"Average"
Max
Rep
2600
8.6
4.5
6.0
0.00
0.00
0.00
Sugar
Beets
(MN)
Maximum
"Average"
Max
rep
2600
19
14
11
0.00
0.00
0.00
Citrus
(FL)
Maximum
"Average"
Max
Rep
2600
274
145
232
0.10
0.06
0.09
The
acute
risk
LOC
is
exceeded
for
all
five
carbaryl
use
scenarios
modeled
at
maximum
label
use
rates,
QUA
average
rates,
and
maximum
reported
(Doane
data)
rates
(Table
16).
Due
to
the
unavailability
of
core
chronic
toxicity
data,
it
is
not
possible
to
evaluate
chronic
risk
to
estuarine/
marine
fish
or
invertebrates
at
this
time.
165
Table
16.
Acute
risk
quotients
for
estuarine/
marine
invertebrates
based
on
a
mysid
LC50
of
5.7
ppb
and
three
sets
of
use
rates,
at
maximum
label
use
rates,
QUA
average
use
rates,
and
maximum
reported
use
rates
Site/
Appl.
Method
Use
Rates
LC50
(ppb)
EEC
Initial/
Peak
(ppb)
(Max
Rates)
Acute
RQ
(EEC/
EC50)
(Max
Rates)
Sweet
Corn
(OH)
Maximum
"Average"
Max
Rep
5.7
46
16
14
8.07
2.81
2.46
Field
Corn
(OH)
Maximum
"Average"
Max
Rep
5.7
28
12
18
4.91
2.10
3.16
Apples
(OR)
Maximum
"Average"
Max
Rep
5.7
8.
6
4.5
6.0
1.51
0.79
1.05
Sugar
Beets
(MN)
Maximum
"Average"
Max
rep
5.7
19
14
11
3.33
2.46
1.93
Citrus
(FL)
Maximum
"Average"
Max
Rep
5.7
274
145
232
48.07
25.44
40.70
Aquatic
Plants
Exposure
to
nontarget
aquatic
plants
may
occur
through
runoff
or
spray
drift
from
adjacent
treated
sites
or
directly
from
such
uses
as
aquatic
weed
or
mosquito
larvae
control.
An
aquatic
plant
risk
assessment
for
acute
risk
is
usually
made
for
aquatic
vascular
plants
from
the
surrogate
duckweed
Lemna
gibba.
Non
vascular
acute
risk
assessments
are
performed
using
either
algae
or
a
diatom,
whichever
is
the
most
sensitive
species.
An
aquatic
plant
risk
assessment
for
acuteendangered
species
is
usually
made
for
aquatic
vascular
plants
from
the
surrogate
duckweed
Lemna
gibba.
To
date,
there
are
no
known
non
vascular
plant
species
on
the
endangered
species
list.
Runoff
and
drift
exposure
is
computed
from
GENEEC.
The
risk
quotient
is
determined
by
dividing
the
pesticide's
initial
or
peak
concentration
in
water
by
the
plant
EC50
value.
Based
on
a
single
core
aquatic
plant
toxicity
study
available,
neither
the
acute
risk
nor
the
endangered
species
LOC
is
exceeded
for
any
of
the
five
use
scenarios
modeled,
at
maximum
label,
QUA
average,
and
maximum
reported
use
rates
(Table
17).
However,
to
fully
assess
carbaryl
risk
to
aquatic
plants,
it
is
recommended
that
toxicity
studies
with
Lemna
gibba,
Anabaena
flos
aquae,
Skeletonema
costatum,
and
a
freshwater
diatom
be
submitted.
166
Table
17.
Risk
quotients
for
aquatic
plants
based
on
a
green
alga
EC50
of
1,1
ppm
and
a
NOAEC
of
0.37
ppm,
at
maximum
label
use
rates,
QUA
average
use
rates,
and
maximum
reported
use
rates
Site/
Appl.
Method
Use
Rates
EC50
(ppb)
NOAEC
(ppb)
EEC
Initial/
Peak
(ppb)
Acute
RQ
(EEC/
EC50)
Acute
Endangered
Species
RQ
(EEC/
NOAEC)
Sweet
Corn
(OH)
Maximum
"Average"
Max
Rep
1100
370
46
16
14
0.04
0.01
0.01
0.12
0.04
0.04
Field
Corn
(OH)
Maximum
"Average"
Max
Rep
1100
370
28
12
18
0.02
0.01
0.02
0.08
0.03
0.05
Apples
(OR)
Maximum
"Average"
Max
Rep
1100
370
8.6
4.5
6.0
0.01
0.00
0.00
0.02
0.01
0.02
Sugar
Beets
(MN)
Maximum
"Average"
Max
rep
1100
370
19
14
11
0.02
0.01
0.01
0.05
0.04
0.03
Citrus
(FL)
Maximum
"Average"
Max
Rep
1100
370
274
145
232
0.25
0.13
0.21
0.74
0.39
0.63
Endangered
Species
The
endangered
species
LOC
for
birds
is
met
or
exceeded
for
72
of
74
nongranular
carbaryl
uses
at
maximum
label
use
rates,
for
18
of
70
carbaryl
uses
at
QUA
average
use
rates,
and
for
25
of
42
maximum
reported
use
rates.
The
acute
endangered
species
LOC
for
mammals
is
met
or
exceeded
for
all
(74)
uses
at
maximum
label
rates,
it
is
exceeded
for
all
(70)
uses
at
QUA
average
rates,
and
it
is
exceeded
for
all
(42)
uses
at
maximum
reported
use
rates.
Based
on
five
use
scenarios
modeled
(sweet
corn,
field
corn,
apples,
sugar
beets,
and
citrus)
for
assessing
risk
to
aquatic
organisms,
the
freshwater
fish
endangered
species
LOC
is
met
or
exceeded
for
four
use
scenarios,
at
maximumlabel,
QUA
average,
and
maximumreported
use
rates.
The
estuarine/
marine
fish
endangered
species
LOC
is
exceeded
for
one
scenario
(citrus),
at
all
three
use
rates
modeled.
The
endangered
species
LOC
for
both
freshwater
and
estuarine/
marine
aquatic
invertebrates
is
exceeded
for
all
five
scenarios
and
all
three
use
rates
modeled.
These
data
indicate
that
over
half
of
carbaryl
uses
pose
an
acute
risk
to
endangered
species
of
birds,
while
all
uses
represent
an
acute
risk
to
endangered
species
of
mammals.
With
regard
to
aquatic
species,
most
carbaryl
uses
are
likely
to
present
an
acute
risk
to
endangered
species
of
freshwater
fish
and
aquatic
invertebrates,
both
freshwater
and
marine/
estuarine
species.
Only
the
highest
use
rates
(citrus)
are
likely
to
pose
an
acute
risk
to
endangered
species
of
marine/
estuarine
fish.
167
Appendix
C:
Toxicity
Assessment
Toxicity
Assessment
Toxicity
testing
reported
in
this
section
is
not
representative
of
the
wide
diversity
of
terrestrial
and
aquatic
organisms
in
the
United
States.
Two
surrogate
bird
species,
the
bobwhite
quail
and
the
mallard
duck,
are
used
to
represent
the
680+
species
of
birds
found
in
this
country.
For
mammals,
acute
studies
are
usually
limited
to
the
Norway
rat
or
the
house
mouse.
Reptiles
are
not
tested,
as
these
are
assumed
to
be
subject
to
similar
toxicological
effects
as
birds.
Of
approximately
100,000
species
of
insects,
spiders,
and
other
terrestrial
arthropods,
toxicity
tests
are
usually
required
only
for
the
honey
bee.
Only
two
surrogate
fish
species
(rainbow
trout
and
bluegill
sunfish)
are
used
to
represent
the
over
2,000
species
of
freshwater
fish
found
in
this
country.
Amphibians
are
not
tested,
as
these
are
assumed
to
be
subject
to
similar
toxicological
effects
as
fish.
One
crustacean,
the
water
flea,
is
used
to
represent
all
freshwater
invertebrates.
Estuarine/
marine
animal
acute
toxicity
testing
is
usually
limited
to
a
crustacean,
a
mollusk,
and
a
fish.
Toxicity
to
Terrestrial
Animals
Birds,
Acute
and
Subacute
Toxicity
Based
on
a
rock
dove
lower
95%
confidence
interval
LD50
of
1,000
mg/
kg
and
a
mallard
LD50
greater
than
2,000
mg/
kg,
technical
carbaryl
can
be
classified
as
slightly
to
practically
nontoxic
to
birds
on
an
acute
basis
(Table
1).
LD50
values
for
carbaryl
as
low
as
16.2
mg/
kg
and
56.2
mg/
kg
have
been
reported
for
the
starling
and
the
red
winged
blackbird,
respectively
(Schafer
et
al.,
1983).
Although
these
data
are
based
on
simple
screening
tests,
and
are
therefore
not
reliable
for
risk
assessment
purposes,
they
do
suggest
that
passerine
birds
may
be
significantly
more
sensitive
to
carbaryl
exposure
than
non
passerine
birds.
The
registrant
is
strongly
encouraged
to
submit
acute
oral
toxicity
tests
with
passerine
avian
species.
The
guideline
71
1
is
fulfilled
(MRID
00160000).
168
Table
1.
Summary
of
avian
acute
oral
toxicity
for
technical
grade
carbaryl
Species
%
ai
LD50
(mg/
kg)
Toxicity
Category
MRID
No.
Author/
Year
Study
Classification
1
Mallard
Duck
(Anas
platyrhynchos)
85
>
2,564
Practically
non
toxic
00160000
Hudson
et
al.
(1984)
Core
Canada
Goose
Branta
canadensis
50
1,790
Slightly
toxic
00160000
Hudson
et
al.
(1984)
Supplemental
Ring
necked
Pheasant
male
(Phasianus
colchicus)
95
>
2,000
Practically
non
toxic
00160000
Hudson
et
al.
(1984)
Supplemental
Ring
necked
Pheasant
female
(Phasianus
colchicus)
480g/
L
707
Moderately
toxic
00160000
Hudson
et
al.
(1984)
Supplemental
Sharp
tailed
grouse
Tympanuchus
phasianellus
85
<
1000
Slightly
toxic
00160000
Hudson
et
al.
(1984)
Supplemental
California
quail
Lophortyx
californicus
480
g/
L
>
2000
Practically
non
toxic
00160000
Hudson
et
al.
(1984)
Supplemental
Rock
Dove
(Columba
livia)
85
1,000
3000
2
Slightly
toxic
to
Practically
non
toxic
00160000
Hudson
et
al.
(1984)
Supplemental
1
Core
study
satisfies
guideline
requirements.
Supplemental
study
is
scientifically
sound,
but
does
not
satisfy
guidelines.
2
95%
confidence
interval
Two
subacute
dietary
studies
using
the
TGAI
are
required
to
establish
the
toxicity
of
carbaryl
to
birds.
The
preferred
test
species
are
mallard
duck
and
bobwhite
quail.
Results
of
these
tests
are
summarized
in
Table
2.
The
LC50
is
higher
than
5000
ppm
for
both
species.
Therefore,
carbaryl
is
categorized
as
practically
nontoxic
to
avian
species
on
a
subacute
dietary
basis.
An
LC50
greater
than
10,000
ppm
has
been
reported
by
Hill
and
Camardese
(1986),
confirming
that
carbaryl's
low
toxicity
to
birds
on
a
subacture,
dietary
basis.
The
guideline
71
2
is
fulfilled
(MRID
00028757,
00022923).
Table
2
:
Summary
of
avian
subacute
dietary
toxicity
for
technical
grade
carbaryl
Species
%
ai
5
Day
LC50
(ppm)
Toxicity
Category
MRID
No.
Author/
Year
Study
Classification
Ring
necked
Pheasant
(Phasianus
calchicus)
99.8
>
5,000
practically
non
toxic
00028757
Hill
et
al.
(1975)
Core
Northern
bobwhite
Quail
(Colinus
virginianus)
99.8
>
5,000
Practically
non
toxic
00028757
Hill
et
al.
(1975)
Core
Japanese
Quail
(Coturnix
japonica)
99.8.
>
5,000
Practically
non
toxic
00022923
Hill
et
al.
(1975)
Supplemental
Mallard
Duck
(Anas
platyrhynchos)
99.8
>
5000
Practically
non
toxic
00022923
Hill
et
al.
(1975)
Core
According
to
the
Ecological
Incident
Information
System
(EIIS)
database
summarizing
6(
a)
2
incident
reports,
bird
kills
attributed
to
carbaryl
and
involving
blackbirds,
ducks,
starlings,
grackles
169
turkey,
and
cardinals
have
been
reported
in
Pennsylvania,
Virginia,
New
Jersey,
North
Carolina
and
Michigan
(#
1002048
001,
#1000802
001,
#1007720
020,
##
1000799
003,
#1004375
004)
.
Birds,
Chronic
Toxicity
Exposure
to
carbaryl
at
levels
equal
to
or
greater
than
1000
ppm
in
the
mallard
duck
results
in
adverse
reproductive
effects,
such
as
decreased
number
of
eggs
produced,
increased
number
of
cracked
eggs,
and
decreased
fertility
(Table
3).
Guideline
71
4
is
fulfilled
(ACC263701;
MRID
00160044).
Table
3.
Summary
of
avian
reproduction
toxicity
for
technical
grade
carbaryl
Species
%
ai
NOAEC
(ppm)
LOAC
Endpoints
MRID.
No.
Author/
Year
Study
Classification
Northern
bobwhite
Quail
(Colinus
virginianus)
99.9
>
3,000
N/
A
00160044
Fletcher
(1986)
Core
Mallard
Duck
(Anas
platyrhynchos)
99.9
300
Number
of
eggs
produced
ACC263701
Fletcher
(1986)
Core
Mammals,
Acute
and
Chronic
As
shown
in
Table
4,
carbaryl
is
categorized
as
moderately
toxic
to
small
mammals
on
an
acute
oral
basis
(LD50
=
301
mg/
kg).
Although
at
this
time
two
generation
rat
reproduction
study
data
are
not
available,
a
LOAEC
of
600
ppm
and
a
NOAEC
of
80
ppm,
based
on
decreased
fetal
body
weights
and
increased
incomplete
ossification
of
multiple
bones
(from
a
rat
prenatal
development
study,
MRID#
44732901),
suggest
that
carbaryl
has
the
potential
for
chronic
effects
in
mammals.
Table
4.
Summary
of
mammalian
toxicity
for
technical
grade
carbaryl
Species
%
ai
Test
Type
Toxicity
Value
Affected
Endpoints
MRID
No.
Laboratory
Rat
(Rattus
norvegicus)
99.0%
Acute
oral
LD50
=
301.0
mg/
kg
Morbidity
00148500
Laboratory
Rat
(Rattus
norvegicus)
99.0%
Prenatal
Development
NOAEC/
LOAEC
80
/
600
ppm
Decreased
fetal
body
weights
and
incomplete
ossification
of
multiple
bones
44732901
Domestic
Dog
(Canis
familiaris)
99.0%
Chronic
NOAEC/
LOAEC
45
/
125
ppm
Decreased
plasma
cholinesterase
40166701
42022801
Incidents
involving
small
mammal
kills
(squirrels,
ground
squirrel,
mole,
rabbit)
have
been
recorded
in
South
Carolina
and
Virginia
(#
1000504
039,
#1000504
039).
170
Insect
Toxicity
Technical
carbaryl
is
categorized
as
highly
toxic
to
bees
on
an
acute
contact
basis
(Table
5).
Guideline
141
1
is
fulfilled
(MRID
00036935,
05001991,
05004151).
Table
5.
Summary
of
honey
bee
acute
contact
toxicity
for
technical
grade
carbaryl
Species
%
ai
Contact
LD50
(µg/
bee)
Oral
LC50
(µg/
bee)
Toxicity
Category
MRID
No.
Author/
Year
Study
Classification
Honey
Bee
(Apis
mellifera)
tech.
1.
3
0.14
Highly
toxic
05001991
Stevenson
(1978)
Core
Honey
Bee
(Apis
mellifera)
tech
2.0
Highly
toxic
00036935
Atkins
et
al.
(1975)
Core
Honey
Bee
(Apis
mellifera)
tech
1.1
0.
11
Highly
toxic
05004151
Stevenson
(1968)
Core
The
topical
LD50
for
alfalfa
leaf
cutter
bee
(Megachile
pacifica
=
M.
rotundata)
=
262.4
µg/
g
(05015678)
(
Lee
&
Brindley
1974).
However,
exposing
leaf
cutter
bees
(Megachilidae),
alkali
bees
(Halictidae),
and
honey
bees
(Apidae)
to
24
hr
residues
from
80%
WP
carbaryl
applied
at
the
rate
of
1
lb/
acre
resulted,
respectively,
in
a
85%,
78%,
and
69%
mortality
rate
(Johansen
1972)
(ID
#05000837).
Some
carbaryl
formulations
can
be
highly
toxic
to
bees
exposed
to
direct
application,
i.
e.
when
bees
are
actively
visiting
blooming
crops
or
weeds.
Residual
toxicity
varies
with
the
crops
and
weather
conditions.
Carbaryl
can
also
be
from
moderately
to
highly
toxic
to
predaceous
arthropods.
These
include
lace
bugs
(Nabidae)
(MRID
#05010807),
big
eyed
bugs
(Geocoridae:
Geocoris)
(MRID
#05010807,
),
lady
beetles
(Coccinellidae:
Coccinella,
Cryptolaemus,
Hippodamia,
Lindorus,
Rhodolia,
Stethorus)
(MRID
#05013372,
05003978,
05005640),
ground
beetles
(Carabidae:
Scarites,
Pterostichus,
Bembidion,
Harpalus)
(MRID
#05008149),
hymenopterous
parasitoids
(Aphytis,
Metaphycus,
Spalangia,
Leptomastix)
(MRID
#05003978,
05005640),
predaceous
mites
(Amblyseius,
Typhlodromus)
(MRID
#05004148,
05013359,
05009346),
and
spiders
(MRID
#05010807).
Bee
kill
incidents
have
been
reported
for
North
Carolina,
California,
and
Washington
(#
1003826
016,
#1003226
021,
#1005855
001,
#1001611
002).
Toxicity
to
Freshwater
Aquatic
Animals
Freshwater
Fish,
Acute
Results
of
toxicity
tests
with
freshwater
fish
are
tabulated
in
Table
6.
Since
the
LC50
values
for
the
species
tested
are
in
the
0.25
20.0
ppm
range,
carbaryl
can
therefore
range
from
highly
to
slightly
toxic
to
freshwater
fish
on
an
acute
basis.
Guidelines
72
1(
a)
and
72
1(
c)
are
fulfilled
(MRID
40098001,
00043115).
171
Table
6.
Summary
of
freshwater
fish
acute
toxicity
for
technical
grade
carbaryl
Species
%
ai
96
hour
LC50
(ppm)
(nominal)
Toxicity
Category
MRID
No.
Author/
Year
Study
Classification
Rainbow
Trout
(Oncorhynchus
mykiss)
99.5
1.
2
Moderately
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Core
Chinook
Salmon
(Oncorhynchus
tshawytacha)
99.5
2.
4
Moderately
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Supplemental
Bluegill
Sunfish
(Lepomis
macrochirus)
99.9
14.0
Slightly
Toxic
00043115
McCann
et
al
(1969)
Core
Bluegill
Sunfish
(Lepomis
macrochirus)
99.9
5.
04
Moderately
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Core
Channel
Catfish
(Ictalurus
punctatus)
99.9
7.
79
Moderately
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Core
Fathead
Minnow
(Pimephales
promelas)
99.5
7.
7
Moderately
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Core
Black
Crappie
(Pomoxis
nigromaculatus)
99.5
2.
6
Moderately
Toxic
40094602
Johnson
&
Finley
(1986)
Core
Atlantic
Salmon
(Salmo
salar)
99.5
0.
25
Highly
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Core
Brown
Trout
(Salmo
trutta)
99.5
6.
3
Moderately
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Core
Brook
Trout
(Salvelinus
fontinalis)
99.5
3.
0
Moderately
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Core
Lake
Trout
(Salvelinus
namaycush)
99.5
0.
69
Highly
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Core
Coho
Salmon
(Oncorhynchus
kisutch)
99.5
2.
4
Moderately
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Core
Yellow
Pearch
(Percs
flavescens)
99.5
0.
35
Highly
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Core
Cutthroat
Trout
(Oncorhynchus
clarki)
99.5
0.
97
Highly
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Core
Largemouth
Bass
(Micropterus
salmoides)
99.5
6.
4
Moderately
Toxic
40094602
Johnson
&
Finley
(1980)
Core
Green
Sunfish
(Lepomis
cyanellus)
99.5
9.
5
Moderately
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Core
Black
Bullhead
(Ictalurus
melas)
99.5
20.0
Slightly
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Core
Longnose
Killifish
(Fundulus
similis)
99.7
1.
6
Moderately
Toxic
40228401
Mayer
(1986)
Supplemental
Carp
(Cyprinus
carpio)
99.5
5.
3
Moderately
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Core
172
Toxicity
was
determined
for
the
typical
end
use
product
as
well,
with
all
LC50
values,
except
one,
ranging
from
1.4
to
49
ppm,
which
indicates
that
carbaryl
can
be
classified
as
slightly
to
moderately
toxic
to
freshwater
fish
(Table
7).
Guidelines
(b)
and
72
1(
d)
are
fulfilled
(MRID
#s
00059202,
00042381,
00151519,
00151417,
42397901,
00124383,
00124391).
Table
7.
Summary
of
freshwater
fish
acute
toxicity
for
carbaryl
(typical
end
use
product)
Species
%
ai
96
hr
LC50
(ppm)
Toxicity
Category
MRID
No.
Author/
Year
Study
Classification
Rainbow
Trout
(Oncorhynchus
mykiss)
44
1.4
Moderately
Toxic
00151417
Sousa
(1985)
Core
Rainbow
Trout
(Oncorhynchus
mykiss)
81.5
3.
3
Moderately
Toxic
42397901
Lintott
(1992)
Core
Rainbow
Trout
(Oncorhynchus
mykiss)
50
3.45
Moderately
Toxic
00124383
McCann
(1971)
Core
Rainbow
Trout
(Oncorhynchus
mykiss)
50
4.5
Moderately
Toxic
00124383
McCann
(1971)
Core
Bluegill
Sunfish
(Lepomis
macrochirus)
30
49.0
Slightly
Toxic
00059202
Mc
Caan
(1970)
Core
Bluegill
Sunfish
(Lepomis
macrochirus)
5
290.0
Practically
Nontoxic
00042381
McCann
(1968)
Core
Bluegill
Sunfish
(Lepomis
macrochirus)
44
9.8
Moderately
Toxic
00151519
Sousa
(1985)
Core
Bluegill
Sunfish
(Lepomis
macrochirus)
50
22.0
Slightly
Toxic
00124391
McCann
(1971)
Core
Freshwater
Fish,
Chronic
Results
of
the
required
early
life
stage
with
fish
are
summarized
in
Table
8,
show
that
carbaryl
has
high
potential
for
chronic
toxicity
to
freshwater
fish.
Exposure
to
680
ppb
can
result
in
growth
effects
to
young.
The
guideline
requirement
72
4(
a)
for
freshwater
fish
is
fulfilled
(TOUCARO5).
Table
8.
Summary
of
freshwater
fish
life
cycle
toxicity
under
flow
through
conditions
for
technical
grade
carbaryl
Species
%
ai
NOAEC/
LOAC
(ppm)
Endpoints
Affected
MRID
No.
Author/
Year
Study
Classification
Fathead
Minnow
(Pimephales
promelas)
99
0.21/
0.68
Reproduction
TOUCARO5
Carlson
(1972)
Core
Amphibians
173
According
to
a
supplemental
study
with
an
end
use
product
containing
50%
carbaryl
(MRID
00160000),
the
LD50
for,
the
bullfrog
(Rana
catesbeiana)
is
greater
than
4,000
mg/
kg,
or
practically
nontoxic.
Freshwater
Invertebrates,
Acute
Since
the
EC50
falls
in
the
range
of
1.7
26
ppb,
carbaryl
is
categorized
as
very
highly
toxic
to
aquatic
invertebrates
on
an
acute
basis
(Table
9).
Toxicity
studies
with
the
typical
end
use
product
show
that
carbaryl
is
very
highly
toxic
to
daphnids,
with
an
EC50
in
the
4.29
13.0
ppb
range
(Table
10).
Guideline
72
2
is
fulfilled
(MRID
#s
40098001,
42397902,
42397903).
Table
9.
Summary
of
freshwater
invertebrate
acute
toxicity
for
technical
grade
carbaryl
Species/
Static
or
Flowthrough
%
ai
48
hour
EC50
(ppb)
(nominal)
Toxicity
Category
MRID
No.
Author/
Year
Study
Classification
Water
flea
(Daphnia
magna)
99.5
5.
6
Very
Highly
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Core
Stonefly
(Classenia
sabulosa)
99.5
96hr
LC50=
5.6
Very
Highly
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Supplemental
Stonefly
(Isogenus
sp.)
99.5
96hr
LC50=
3.6
Very
Highly
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Supplemental
Stonefly
(Pteronarcella
badia)
99.5
96hr
LC50=
1.7
Very
Highly
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Supplemental
Scud
(Gammarus
fasciatus)
99.5
96hr
EC50=
26
Very
Highly
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Core
Table
10.
Acute
toxicity
to
invertebrates
(TEP)
Species
%
ai
48
hour
EC50
(ppb)
Toxicity
category
MRID
No.
Author/
Year
Study
Classification
Water
flea
(Daphnia
magna)
49.0%
7.1
Very
highly
toxic
00150538
Nicholson
and
Surprenant
(1985)
Supplemental
Water
flea
(Daphnia
magna)
43.9%
13.0
Very
highly
toxic
00150540
Nicholson
and
Surprenant
(1985)
Supplemental
Water
flea
(Daphnia
magna)
47.3%
4.29
Very
highly
toxic
42432401
Lintott
(1992)
Supplemental
Water
flea
(Daphnia
magna)
43.7%
6.66
Very
highly
toxic
42397902
Lintott
(1992)
Core
174
Water
flea
(Daphnia
magna)
81.5%
7.2
Very
highly
toxic
42397903
Lintott
(1992)
Core
Freshwater
Invertebrate,
Chronic
A
21
day
toxicity
study
preformed
with
the
water
flea
estimated
a
NOAEC
and
a
LOAEC
of
1.5
ppb
and
3.3
ppb,
respectively,
based
on
affected
reproduction
(Table
11).
Guideline
72
4(
b)
for
freshwater
invertebrates
is
fulfilled
(MRID
00150901).
Table
11.
Summary
of
freshwater
aquatic
invertebrate
life
cycle
toxicity
for
technical
grade
carbaryl
Species
%
ai
21
day
NOAEC/
LOAEC
(ppb)
Endpoints
Affected
MRID
No.
Author/
Year
Study
Classification
Water
flea
(Daphnia
magna)
99.0%
1.5/
3.3
Reproduction
00150901
Surprenant
(1985)
Core
Toxicity
to
Estuarine
and
Marine
Animals
Estuarine/
Marine
Fish,
Acute
Since
the
minnow
LC50
is
2.6
ppm
(Table
12),
carbaryl
is
categorized
as
moderately
toxic
to
estuarine/
marine
fish
on
an
acute
basis.
The
guideline
72
3(
a)
is
fulfilled
(MRID
42372801).
Table
12.
Summary
of
estuarine/
marine
fish
acute
toxicity
for
technical
grade
carbaryl
Species/
Static
%
ai
96
hour
LC50
(ppm)
(nominal)
Toxicity
Category
MRID
No.
Author/
Year
Study
Classification
Sheepshead
Minnow
(Cyprinodon
variegatus)
99
2.2
Moderately
Toxic
00150539
Sousa
and
Surprenant
(1985)
Supplemental
Sheepshead
Minnow
(Cyprinodon
variegatus)
99.7%
2.6
Moderately
Toxicc
42372801
Lintott
(1992)
Core
Estuarine
and
Marine
Fish,
Chronic
An
estuarine/
marine
fish
early
life
stage
toxicity
test
using
the
TGAI
is
required
for
carbaryl
because
the
end
use
product
is
expected
to
be
transported
to
this
environment
from
the
intended
use
site.
Carbaryl
is
registered
for
ghost
and
mud
shrimp
control
in
oyster
beds
in
Washington
and
has
the
potential
to
affect
nontarget
fish
and
invertebrates
outside
the
application
sites.
In
addition,
the
pesticide
uses
are
such
that
its
presence
in
water
is
likely
to
be
continuous
(multiple
applications),
175
and
chronic
concerns
have
been
noted
for
freshwater
fish
and
marine
and
freshwater.
At
this
point,
the
guideline
72
4(
a)
for
estuarine/
marine
fish
is
not
fulfilled.
Estuarine
and
Marine
Invertebrates,
Acute
As
shown
in
Table
13,
the
96
hour
mysid
shrimp
LC50
for
technical
carbaryl
falls
is
5.7
ppb
(MRID
42343401).
Thus,
this
chemical
is
categorized
as
very
highly
toxic
to
estuarine/
marine
shrimp
species
on
an
acute
basis.
By
contrast,
carbaryl
is
moderately
toxicity
to
the
oyster
(LC50
=
2.7
ppm,
MRID
00148221).
Guidelines
72
3(
b)
and
72
3(
c)
are
fulfilled.
Table
13.
Summary
of
estuarine/
marine
invertebrate
acute
toxicity
for
technical
grade
carbaryl
Species
%
ai.
48
hour
LC50
(ppb)
Toxicity
Category
MRID
No.
Author/
Year
Study
Classification
Brown
Shrimp
(Penaeus
aztecus)
99.7
1.
5
Very
Highly
Toxic
40228401
Mayer
(1986)
Supplemental
Mysid
(Mysidopsis
bahia)
99
96
hr
LC50
=
6.7
Very
Highly
Toxic
00150544
Hoberg
and
Surprenant
(1985)
Supplemental
Mysid
(Mysidopsis
bahia)
99.7
96
hr
LC50
=
5.7
Very
Highly
Toxic
42343401
Lintott
(1992)
Core
Glass
Shrimp
(Palaemonetes
kadiakensis)
99.5
5.
6
Very
Highly
Toxic
40098001
Mayer
&
Ellersieck
(1986)
Supplemental
Grass
Shrimp
(Palaemonetes
pugio)
99.7
28
Very
Highly
Toxic
40228401
Mayer
(1986)
Supplemental
Pink
Shrimp
(Penaeus
duorarum)
99.7
32
Very
Highly
Toxic
40228401
Mayer
(1986)
Supplemental
Eastern
Oyster
(Crassostrea
virginica)
99.7
96
hr
LC50>
2
Very
Highly
Toxic
40228401
Mayer
(1986)
Core
Eastern
Oyster
(Crassostrea
virginica)
99
2700
Moderately
Toxic
00148221
Surprenant,
et
al.
(1985)
Core
Blue
Crab
(Callinectes
sapidus)
99.7
320
Highly
Toxic
40228401
Mayer
(1986)
Supplemental
Fairy
Shrimp
95.3%
170
Highly
toxic
40094602
Mayer
(1986)
Supplemental
Eastern
Oyster
(Crassostria
virginica)
95.0%
>1,000
Moderately
toxic
40228401
Mayer
(1986)
Supplemental
Results
of
toxicity
testing
using
the
typical
end
use
product
are
summarized
in
Table
14.
Carbaryl
TEPs
are
highly
toxic
to
mysids,
LC50
values
ranging
from
9.3
to
20.2
ppb
(MRID
#s
42397904,
42565601,
and
42343402),
and
slightly
toxic
to
oysters
(LC50
=
23.6
ppm,
MRID
42597301).
Guidelines
72
3(
e)
and
72
3(
f)
are
fulfilled.
176
Table
14.
Summary
of
estuarine/
marine
invertebrate
acute
toxicity
for
TEP
Species
%
ai.
48
hour
LC50
(ppb)
Toxicity
Category
MRID
No.
Author/
Year
Study
Classification
Mysid
(Mysidopsis
bahia)
81.5
9.
6
Very
Highly
Toxic
42397904
Lintott
(1992)
Core
Mysid
(Mysidopsis
bahia)
81.5
9.
3
Very
Highly
Toxic
42565601
McElwee
and
Lintott
(1992)
Core
Mysid
(Mysidopsis
bahia)
43.7%
96
hr
LC50
=
20.2
Very
Highly
Toxic
42343402
Lintott
(1992)
Core
Eastern
Oyster
(Crassostrea
virginica)
43.3%
96
hr
LC50
=
23,600
Slightly
Toxic
42597301
Lintott
(1992)
Supplemental
Estuarine
and
Marine
Invertebrate,
Chronic
There
are
no
available
chronic
toxicity
data
for
estuarine/
marine
invertebrates.
The
guideline
72
4(
b)
for
estuarine/
marine
invertebrates
is
no
fulfilled.
1
Naphthol
Toxicity
to
Aquatic
Organisms
The
major
metabolite
of
carbaryl
degradation
by
abiotic
and
microbially
mediated
processes
is
1
naphthol.
As
summarized
in
Table
15,
1
naphthol
is
categorized
as
moderately
to
highly
toxic
to
aquatic
organisms
on
an
acute
basis,
LC50
values
ranging
from
0.75
to
1.6
ppm
for
freshwater
fish,
from
1.2
to
1.8
ppm
for
estuarine/
marine
fish,
from
0.70
to
0.73
ppm
for
freshwater
invertebrates,
and
from
0.21
to
2.5
ppm
for
estuarine/
marine
invertebrates.
Terrestrial
Plants
Toxicity
testing
of
terrestrial
plants
is
required
for
non
herbicide
pesticides
when
the
label
warns
that
nontarget
plants
could
be
adversely
affected.
Carbaryl
can
be
used
as
a
fruit
thinning
agent
on
apples
and
pears.
However,
the
label
cautions
that
the
product
may
result
in
fruit
deformity
under
certain
environmental
conditions.
The
label
also
cautions
that
application
to
wet
foliage
or
during
periods
of
high
humidity
may
cause
injury
to
tender
foliage.
Label
language
indicates
that
carbaryl
should
not
be
used
on
Boston
ivy,
Virginia
creeper,
and
maidenhair
fern
due
to
potential
injury.
Incidents
have
also
been
recorded
for
vegetable
crops
(tomatoes,
potatoes,
cabbage,
broccoli,
pumpkin,
squash,
cucumbers)
in
New
York
and
Pennsylvania
(#
1009262
128;
#1009305
001).
Guideline
122
1
is
not
fulfilled.
177
Table
15
Summary
of
aquatic
organisms
acute
toxicity
for
carbaryl
degradate
alpha
naphthol
Species
96
hour
LC50
(ppm)
(nominal)
Toxicity
Category
MRID
No.
Author/
Year
Study
Classification
Rainbow
Trout
(Oncorhynchus
mykiss)
1.4
Moderately
Toxic
40955204
Surprenant
(1988)
Core
Rainbow
Trout
(Oncorhynchus
mykiss)
1.6
Moderately
Toxic
00164307
Surprenant
(1986)
Supplemental
Bluegill
Sunfish
(Lepomis
macrochirus)
0.76
Highly
Toxic
40955203
Surprenant
(1988)
Core
Bluegill
Sunfish
(Lepomis
macrochirus)
0.75
Highly
Toxic
00164305
Surprenant
(1986)
Supplemental
Sheepshead
Minnow
(Cyprinodon
variegatus)
1.2
Moderately
Toxic
40955201
Surprenant
(1988)
Core
Sheepshead
Minnow
(Cyprinodon
variegatus)
1.8
Moderately
Toxic
00164306
Surprenant
(1986)
Supplemental
Waterflea
(Daphnia
magna)
48
hr
LC50
=
0.73
Highly
Toxic
40955205
Surprenant
(1988)
Core
Waterflea
(Daphnia
magna)
48
hr
LC50
=
0.70
Highly
Toxic
00164310
Surprenant
(1986)
Supplemental
Mysid
(Mysidopsis
bahia)
0.21
Highly
Toxic
40955202
Surprenant
(1988)
Core
Mysid
(Mysidopsis
bahia)
0.20
Highly
Toxic
00164309
Surprenant
(1986)
Supplemental
Eastern
Oyster
(Crassostrea
virginica)
48
hr
LC50
=
2.1
Moderately
Toxic
00164308
Surprenant
(1986)
Core
Aquatic
Plants
Aquatic
plant
testing
is
recommended
for
all
pesticides
having
outdoor
uses
(Keehner.
July
1999).
The
tests
are
performed
on
species
from
a
cross
section
of
the
nontarget
aquatic
plant
population.
The
preferred
test
species
are
duckweed
(Lemna
gibba),
marine
diatom
(Skeletonema
costatum),
freshwater
blue
green
algae
(Anabaena
flos
aquae),
freshwater
green
alga
(Selenastrum
capricornutum),
and
a
freshwater
diatom.
Toxicity
testing
for
aquatic
plant
species
is
required
for
carbaryl
because
of
its
registered
forestry
uses.
Data
based
on
a
single
available
core
toxicity
study
with
the
green
alga
Pseudokirchneria
subcapitata
(formerly
Selenastrum
capricornutum)
indicates
that
the
LC50
and
NOAEC
are,
respectively,
1.1
ppm
and
0.37
ppm
(MRID
#42372802).
Guideline
122
2
is
not
fulfilled.
178
Appendix
D:
ELL
FATE
Description
and
example
worksheet
ELL
Fate
Version
1.2
Developed
by
Laurence
Libelo.
February,
1999
This
spreadsheet
based
model
calculates
the
decay
of
a
chemical
applied
to
foliar
surfaces
for
single
or
multiple
applications.
I
t
uses
the
same
principle
as
the
batch
code
models
FATE
and
TERREEC
for
calculating
terrestrial
estimates
exposure
(TEEC)
concentrations
on
plant
surfaces
following
application.
A
first
order
decay
assumption
is
used
to
determine
the
concentration
at
each
day
after
initial
application
based
on
the
concentration
resulting
from
the
initial
and
additional
applications.
The
decay
is
calculated
by
from
the
first
order
rate
equation:
CT
=
Cie
kT
or
in
integrated
form:
ln
(CT/
Ci)
=
kT
Where
CT
=
concentration
at
time
T
Ci
=
initial
concentration
k
=
reaction
rate
constant
T
=
time
The
program
calculates
concentration
on
each
type
of
surface
on
a
daily
interval
for
one
year.
The
maximum
concentration
during
the
year
and
the
average
concentration
during
the
first
56
days
are
calculated.
The
inputs
used
to
calculate
the
amount
of
the
chemical
present
are
in
highlighted
in
yellow
on
the
spread
sheet.
Outputs
are
in
blue.
The
inputs
required
are:
Application
Rate:
Half
life:
Frequency
of
Application:
Maximum
#
Application
per
year:
The
calculated
concentrations
are
used
to
calculate
Avian
and
Mammalian
RQ
values.
The
maximum
calculated
concentration
is
divided
by
user
input
values
of
Chronic
No
Observable
Adverse
Effects
Level
and
acute
LC50
to
give
RQs
for
each
type
of
plant
surface.
The
rat
LC
50
is
calculated
by
dividing
the
mammalian
LD
50
by
0.05
(to
correct
for
actual
food
consumption)
For
15g,
35g
and
1000
g
mammals
the
RQ
values
are
calculated
by
dividing
the
maximum
concentration
for
each
surface
by
the
LD
50
or
NOAEL
corrected
for
consumption
(0.95,
0.66
and
.15
body
wt.
for
herbivores
and
)
insectivores
and
0.21,
0.15
and
0.3
body
wt.
for
granivore)
The
number
of
days
that
the
input
value
of
Chronic
No
Observable
Adverse
Effects
Level
and
acute
LC50
are
exceeded
in
the
first
56
days
is
calculated
by
comparing
the
input
value
to
the
calculated
concentration.
A
graph
of
concentration
on
each
plant
surface
vs
time
is
plotted
and
a
"level
of
concern"
line
can
be
added
at
a
user
specified
level.
The
maximum
single
application
which
can
be
applied
and
not
exceed
the
toxicity
input
values
if
calculated
by
dividing
the
input
value
by
the
Kenaga
maximum
concentration
for
Short
Grass
(240).
179
Carbaryl
Chemical
Name:
Citrus
Use
Formulation
Inputs
lbs
a.
i./
acre
5
Application
Rate
days
35
Half
life
days
14
Frequency
of
Application
4
Maximum
#
Apps./
Year
Outputs
56
day
Average
Maximum
Concentration
Concentration
(PPM)
(PPM)
2079.15
3320.98
Short
Grass
#
days
952.94
1522.12
Tall
Grass
Exceeded
1169.52
1868.05
Broadleaf
plants/
Insects
on
short
grass
129.95
207.56
Seeds
(in
first
56)
0
5000
Acute
LC
50
(ppm)
Avian
Max
Single
Application
56
300
Chronic
NOAEC
(ppm)
which
does
NOT
exceed
20.833
Avian
Acute
Chronic
RQ
Acute
RQ
(lb
a.
i.)
1.250
Avian
Chronic
(Max.
res.
mult.
apps.)
11.07
0.66
Short
Grass
8.36
Mammalian
Acute
#
days
5.07
0.30
Tall
Grass
0.33
Mammalian
Chronic
Exceeded
6.23
0.37
Broadleaf
plants/
Insects
on
short
grass
0.69
0.04
Seeds
(in
first
56)
6020
Rat
Calculated
LC
50
(ppm)
56
301
Acute
LD
50
(mg/
kg)
Mammalian
56
80
Chronic
NOAEL
(mg/
kg)
1000
g
mammal
35
g
mammal
15
g
mammal
Rat
Chronic
Rat
Acute
Dietary
Dietary
Acute
RQ
Acute
RQ
Acute
RQ
RQ
RQ
(mult.
apps)
(mult.
apps)
(mult.
apps)
41.51
0.55
1.65
7.28
10.48
Short
Grass
19.03
0.25
0.76
3.34
4.80
Broadleaf
plants/
insects
23.35
0.31
0.93
4.10
5.90
Large
Insects
2.59
0.03
0.02
0.10
0.14
Seeds
(granivore)
180
Appendix
E:
Examples
of
PRZM
Standard
Pond
Input
Files
***
PRZM3
Input
File
for
INDEX
RESERVOIR,
IROHCORN1.
inp
converted
3/
30/
2000
***
***
Modeler:
S.
Abel
***
***
Modified
for
CARBARYL
by
Laurence
Libelo,
6/
20/
00
(standard
pond
on
7/
14/
2000)
***
Manning's
N
values
for
cornstalk
residue,
fallow
surface,
1
ton/
acre
***
***
Cardington
silt
loam
is
not
one
of
the
benchmark
soils
***
***
Benchmark
soils
include:
blount;
crosby;
pewamo;
miami;
brookston;
glynwood
***
***
miamian;
morley;
bennington;
and
fincastle
***
***
IR
Spray
Drift:
Aerial:
0.16;
Orchard
air
blast:
0.063;
Ground
spray:
0.064
***
***
Standard
Pond
Spray
Drift:
Aerial
=
0.05;
Ground
spray
=
0.01
***
Application
efficiency:
aerial
=
0.95;
ground
spray
=
0.99
***
***
PCA
for
corn
=
0.46
***
CARBARYL
Location:
OH
Crop:
corn
MLRA
111
***
RECORD
3
***
0.72
0.30
0
15.00
1
3
***
RECORED
4
***
4
***
RECORD
7
***
0.37
0.43
0.50
10.0
5.80
3
6.00
354.0
***
RECORD
8
***
1
***
RECORD
9
***
1
0.25
90.00
100.00
3
91
85
88
0.00
100.00
***
RECORD
9A
***
1
3
***
RECORD
9B,
C,
D
0101
1605
1110
0.50
0.25
0.30
0.02
0.02
0.02
***
RECORD
10
***
36
***
RECORD
11
*
160548
260948
111048
1
160549
260949
111049
1
160550
260950
111050
1
160551
260951
111051
1
160552
260952
111052
1
160553
260953
111053
1
160554
260954
111054
1
160555
260955
111055
1
160556
260956
111056
1
160557
260957
111057
1
160558
260958
111058
1
160559
260959
111059
1
160560
260960
111060
1
160561
260961
111061
1
160562
260962
111062
1
160563
260963
111063
1
160564
260964
111064
1
160565
260965
111065
1
160566
260966
111066
1
160567
260967
111067
1
160568
260968
111068
1
160569
260969
111069
1
160570
260970
111070
1
160571
260971
111071
1
160572
260972
111072
1
160573
260973
111073
1
160574
260974
111074
1
160575
260975
111075
1
160576
260976
111076
1
160577
260977
111077
1
160578
260978
111078
1
160579
260979
111079
1
160580
260980
111080
1
160581
260981
111081
1
160582
260982
111082
1
160583
260983
111083
1
***
RECORD
12
***
"average"
Application:
ground
spray
2
apps
@
3.4
lb
a.
i./
acre
***
Application
by
ground
spray
8
apps
@
2
lb
a.
i./
acre
***
RECORD
13
***
108
1
0
0
***
RECORD
15
***
181
Carbaryl
Chemical
Kd:
3.0
(Silt
Loam
Soil);
ASM
T1/
2
=
12
days;
AnSM
T1/
2
=
24
days
***
RECORD
16
***
300448
0
2
0.00
1.12
0.95
0.05
140548
0
2
0.00
1.12
0.95
0.05
280548
0
2
0.00
1.12
0.95
0.05
300449
0
2
0.00
1.12
0.95
0.05
140549
0
2
0.00
1.12
0.95
0.05
280549
0
2
0.00
1.12
0.95
0.05
300450
0
2
0.00
1.12
0.95
0.05
140550
0
2
0.00
1.12
0.95
0.05
280550
0
2
0.00
1.12
0.95
0.05
300451
0
2
0.00
1.12
0.95
0.05
140551
0
2
0.00
1.12
0.95
0.05
280551
0
2
0.00
1.12
0.95
0.05
300452
0
2
0.00
1.12
0.95
0.05
140552
0
2
0.00
1.12
0.95
0.05
280552
0
2
0.00
1.12
0.95
0.05
300453
0
2
0.00
1.12
0.95
0.05
140553
0
2
0.00
1.12
0.95
0.05
280553
0
2
0.00
1.12
0.95
0.05
300454
0
2
0.00
1.12
0.95
0.05
140554
0
2
0.00
1.12
0.95
0.05
280554
0
2
0.00
1.12
0.95
0.05
300455
0
2
0.00
1.12
0.95
0.05
140555
0
2
0.00
1.12
0.95
0.05
280555
0
2
0.00
1.12
0.95
0.05
300456
0
2
0.00
1.12
0.95
0.05
140556
0
2
0.00
1.12
0.95
0.05
280556
0
2
0.00
1.12
0.95
0.05
300457
0
2
0.00
1.12
0.95
0.05
140557
0
2
0.00
1.12
0.95
0.05
280557
0
2
0.00
1.12
0.95
0.05
300458
0
2
0.00
1.12
0.95
0.05
140558
0
2
0.00
1.12
0.95
0.05
280558
0
2
0.00
1.12
0.95
0.05
300459
0
2
0.00
1.12
0.95
0.05
140559
0
2
0.00
1.12
0.95
0.05
280559
0
2
0.00
1.12
0.95
0.05
300460
0
2
0.00
1.12
0.95
0.05
140560
0
2
0.00
1.12
0.95
0.05
280560
0
2
0.00
1.12
0.95
0.05
300461
0
2
0.00
1.12
0.95
0.05
140561
0
2
0.00
1.12
0.95
0.05
280561
0
2
0.00
1.12
0.95
0.05
300462
0
2
0.00
1.12
0.95
0.05
140562
0
2
0.00
1.12
0.95
0.05
280562
0
2
0.00
1.12
0.95
0.05
300463
0
2
0.00
1.12
0.95
0.05
140563
0
2
0.00
1.12
0.95
0.05
280563
0
2
0.00
1.12
0.95
0.05
300464
0
2
0.00
1.12
0.95
0.05
140564
0
2
0.00
1.12
0.95
0.05
280564
0
2
0.00
1.12
0.95
0.05
300465
0
2
0.00
1.12
0.95
0.05
140565
0
2
0.00
1.12
0.95
0.05
280565
0
2
0.00
1.12
0.95
0.05
300466
0
2
0.00
1.12
0.95
0.05
140566
0
2
0.00
1.12
0.95
0.05
280566
0
2
0.00
1.12
0.95
0.05
300467
0
2
0.00
1.12
0.95
0.05
140567
0
2
0.00
1.12
0.95
0.05
280567
0
2
0.00
1.12
0.95
0.05
300468
0
2
0.00
1.12
0.95
0.05
140568
0
2
0.00
1.12
0.95
0.05
280568
0
2
0.00
1.12
0.95
0.05
300469
0
2
0.00
1.12
0.95
0.05
140569
0
2
0.00
1.12
0.95
0.05
280569
0
2
0.00
1.12
0.95
0.05
300470
0
2
0.00
1.12
0.95
0.05
140570
0
2
0.00
1.12
0.95
0.05
280570
0
2
0.00
1.12
0.95
0.05
300471
0
2
0.00
1.12
0.95
0.05
140571
0
2
0.00
1.12
0.95
0.05
280571
0
2
0.00
1.12
0.95
0.05
300472
0
2
0.00
1.12
0.95
0.05
140572
0
2
0.00
1.12
0.95
0.05
280572
0
2
0.00
1.12
0.95
0.05
300473
0
2
0.00
1.12
0.95
0.05
140573
0
2
0.00
1.12
0.95
0.05
280573
0
2
0.00
1.12
0.95
0.05
182
300474
0
2
0.00
1.12
0.95
0.05
140574
0
2
0.00
1.12
0.95
0.05
280574
0
2
0.00
1.12
0.95
0.05
300475
0
2
0.00
1.12
0.95
0.05
140575
0
2
0.00
1.12
0.95
0.05
280575
0
2
0.00
1.12
0.95
0.05
300476
0
2
0.00
1.12
0.95
0.05
140576
0
2
0.00
1.12
0.95
0.05
280576
0
2
0.00
1.12
0.95
0.05
300477
0
2
0.00
1.12
0.95
0.05
140577
0
2
0.00
1.12
0.95
0.05
280577
0
2
0.00
1.12
0.95
0.05
300478
0
2
0.00
1.12
0.95
0.05
140578
0
2
0.00
1.12
0.95
0.05
280578
0
2
0.00
1.12
0.95
0.05
300479
0
2
0.00
1.12
0.95
0.05
140579
0
2
0.00
1.12
0.95
0.05
280579
0
2
0.00
1.12
0.95
0.05
300480
0
2
0.00
1.12
0.95
0.05
140580
0
2
0.00
1.12
0.95
0.05
280580
0
2
0.00
1.12
0.95
0.05
300481
0
2
0.00
1.12
0.95
0.05
140581
0
2
0.00
1.12
0.95
0.05
280581
0
2
0.00
1.12
0.95
0.05
300482
0
2
0.00
1.12
0.95
0.05
140582
0
2
0.00
1.12
0.95
0.05
280582
0
2
0.00
1.12
0.95
0.05
300483
0
2
0.00
1.12
0.95
0.05
140583
0
2
0.00
1.12
0.95
0.05
280583
0
2
0.00
1.12
0.95
0.05
***
Record
17
***
0.0
3
0
***
RECORD
18
***
0.0
0.0
0.00
***
RECORD
19
***
Soil
Series:
Cardington
silt
loam;
Hydrogic
Group
C
***
RECORD
20
***
100.00
0
0
0
0
0
0
0
0
0
***
RECORD
26
***
0.00
0.00
00.00
***
RECORD
33
***
2
***
RECORD
34,36,37
1
22.000
1.600
0.294
0.000
0.000
0.000
0.058
0.058
0.000
0.200
0.294
0.086
1.160
3.0
2
78.000
1.650
0.147
0.000
0.000
0.000
0.029
0.029
0.000
1.000
0.147
0.087
0.174
3.0
0
YEAR
10
YEAR
10
YEAR
10
1
1
1
7
YEAR
PRCP
TSER
0
0
RUNF
TSER
0
0
INFL
TSER
1
1
ESLS
TSER
0
0
1.
E3
RFLX
TSER
0
0
1.
E5
EFLX
TSER
0
0
1.
E5
RZFX
TSER
0
0
1.
E5
***
PRZM3
Input
File
for
INDEX
RESERVOIR,
IROHCORN1.
inp
converted
3/
30/
2000
***
***
Modeler:
S.
Abel
***
***
Modified
for
CARBARYL
by
Laurence
Libelo,
6/
20/
00
(standard
pond
on
7/
14/
2000)
***
***
Use
rate
changed
to
QUA
(July
21,
1998
QUA
Report)
AVERAGE
VALUES
on
2/
23/
01
***
***
Manning's
N
values
for
cornstalk
residue,
fallow
surface,
1
ton/
acre
***
***
Cardington
silt
loam
is
not
one
of
the
benchmark
soils
***
***
Benchmark
soils
include:
blount;
crosby;
pewamo;
miami;
brookston;
glynwood
***
***
miamian;
morley;
bennington;
and
fincastle
***
***
IR
Spray
Drift:
Aerial:
0.16;
Orchard
air
blast:
0.063;
Ground
spray:
0.064
***
***
Standard
Pond
Spray
Drift:
Aerial
=
0.05;
Ground
spray
=
0.01
***
Application
efficiency:
aerial
=
0.95;
ground
spray
=
0.99
***
***
PCA
for
corn
=
0.46
***
CARBARYL
Location:
OH
Crop:
corn
MLRA
111
***
RECORD
3
***
0.72
0.30
0
15.00
1
3
***
RECORED
4
***
183
4
***
RECORD
7
***
0.37
0.43
0.50
10.0
5.80
3
6.00
354.0
***
RECORD
8
***
1
***
RECORD
9
***
1
0.25
90.00
100.00
3
91
85
88
0.00
100.00
***
RECORD
9A
***
1
3
***
RECORD
9B,
C,
D
0101
1605
1110
0.50
0.25
0.30
0.02
0.02
0.02
***
RECORD
10
***
36
***
RECORD
11
*
160548
260948
111048
1
160549
260949
111049
1
160550
260950
111050
1
160551
260951
111051
1
160552
260952
111052
1
160553
260953
111053
1
160554
260954
111054
1
160555
260955
111055
1
160556
260956
111056
1
160557
260957
111057
1
160558
260958
111058
1
160559
260959
111059
1
160560
260960
111060
1
160561
260961
111061
1
160562
260962
111062
1
160563
260963
111063
1
160564
260964
111064
1
160565
260965
111065
1
160566
260966
111066
1
160567
260967
111067
1
160568
260968
111068
1
160569
260969
111069
1
160570
260970
111070
1
160571
260971
111071
1
160572
260972
111072
1
160573
260973
111073
1
160574
260974
111074
1
160575
260975
111075
1
160576
260976
111076
1
160577
260977
111077
1
160578
260978
111078
1
160579
260979
111079
1
160580
260980
111080
1
160581
260981
111081
1
160582
260982
111082
1
160583
260983
111083
1
***
RECORD
12
***
Application
by
ground
spray
Rate
=
"average"
from
QUA
memo
(July
21,
1998)
2
apps
@
1
lb
a.
i./
acre
***
Application
by
ground
spray
8
apps
@
2
lb
a.
i./
acre
***
RECORD
13
***
72
1
0
0
***
RECORD
15
***
Carbaryl
Chemical
Kd:
3.0
(Silt
Loam
Soil);
ASM
T1/
2
=
12
days;
AnSM
T1/
2
=
24
days
***
RECORD
16
***
300448
0
2
0.00
1.68
0.95
0.05
140548
0
2
0.00
1.68
0.95
0.05
300449
0
2
0.00
1.68
0.95
0.05
140549
0
2
0.00
1.68
0.95
0.05
300450
0
2
0.00
1.68
0.95
0.05
140550
0
2
0.00
1.68
0.95
0.05
300451
0
2
0.00
1.68
0.95
0.05
140551
0
2
0.00
1.68
0.95
0.05
300452
0
2
0.00
1.68
0.95
0.05
140552
0
2
0.00
1.68
0.95
0.05
300453
0
2
0.00
1.68
0.95
0.05
140553
0
2
0.00
1.68
0.95
0.05
300454
0
2
0.00
1.68
0.95
0.05
140554
0
2
0.00
1.68
0.95
0.05
300455
0
2
0.00
1.68
0.95
0.05
140555
0
2
0.00
1.68
0.95
0.05
184
300456
0
2
0.00
1.68
0.95
0.05
140556
0
2
0.00
1.68
0.95
0.05
300457
0
2
0.00
1.68
0.95
0.05
140557
0
2
0.00
1.68
0.95
0.05
300458
0
2
0.00
1.68
0.95
0.05
140558
0
2
0.00
1.68
0.95
0.05
300459
0
2
0.00
1.68
0.95
0.05
140559
0
2
0.00
1.68
0.95
0.05
300460
0
2
0.00
1.68
0.95
0.05
140560
0
2
0.00
1.68
0.95
0.05
300461
0
2
0.00
1.68
0.95
0.05
140561
0
2
0.00
1.68
0.95
0.05
300462
0
2
0.00
1.68
0.95
0.05
140562
0
2
0.00
1.68
0.95
0.05
300463
0
2
0.00
1.68
0.95
0.05
140563
0
2
0.00
1.68
0.95
0.05
300464
0
2
0.00
1.68
0.95
0.05
140564
0
2
0.00
1.68
0.95
0.05
300465
0
2
0.00
1.68
0.95
0.05
140565
0
2
0.00
1.68
0.95
0.05
300466
0
2
0.00
1.68
0.95
0.05
140566
0
2
0.00
1.68
0.95
0.05
300467
0
2
0.00
1.68
0.95
0.05
140567
0
2
0.00
1.68
0.95
0.05
300468
0
2
0.00
1.68
0.95
0.05
140568
0
2
0.00
1.68
0.95
0.05
300469
0
2
0.00
1.68
0.95
0.05
140569
0
2
0.00
1.68
0.95
0.05
300470
0
2
0.00
1.68
0.95
0.05
140570
0
2
0.00
1.68
0.95
0.05
300471
0
2
0.00
1.68
0.95
0.05
140571
0
2
0.00
1.68
0.95
0.05
300472
0
2
0.00
1.68
0.95
0.05
140572
0
2
0.00
1.68
0.95
0.05
300473
0
2
0.00
1.68
0.95
0.05
140573
0
2
0.00
1.68
0.95
0.05
300474
0
2
0.00
1.68
0.95
0.05
140574
0
2
0.00
1.68
0.95
0.05
300475
0
2
0.00
1.68
0.95
0.05
140575
0
2
0.00
1.68
0.95
0.05
300476
0
2
0.00
1.68
0.95
0.05
140576
0
2
0.00
1.68
0.95
0.05
300477
0
2
0.00
1.68
0.95
0.05
140577
0
2
0.00
1.68
0.95
0.05
300478
0
2
0.00
1.68
0.95
0.05
140578
0
2
0.00
1.68
0.95
0.05
300479
0
2
0.00
1.68
0.95
0.05
140579
0
2
0.00
1.68
0.95
0.05
300480
0
2
0.00
1.68
0.95
0.05
140580
0
2
0.00
1.68
0.95
0.05
300481
0
2
0.00
1.68
0.95
0.05
140581
0
2
0.00
1.68
0.95
0.05
300482
0
2
0.00
1.68
0.95
0.05
140582
0
2
0.00
1.68
0.95
0.05
300483
0
2
0.00
1.68
0.95
0.05
140583
0
2
0.00
1.68
0.95
0.05
***
Record
17
***
0.0
3
0
***
RECORD
18
***
0.0
0.0
0.00
***
RECORD
19
***
Soil
Series:
Cardington
silt
loam;
Hydrogic
Group
C
***
RECORD
20
***
100.00
0
0
0
0
0
0
0
0
0
***
RECORD
26
***
0.00
0.00
00.00
***
RECORD
33
***
2
***
RECORD
34,36,37
1
22.000
1.600
0.294
0.000
0.000
0.000
0.058
0.058
0.000
0.200
0.294
0.086
1.160
3.0
2
78.000
1.650
0.147
0.000
0.000
0.000
0.029
0.029
0.000
1.000
0.147
0.087
0.174
3.0
185
0
YEAR
10
YEAR
10
YEAR
10
1
1
1
7
YEAR
PRCP
TSER
0
0
RUNF
TSER
0
0
INFL
TSER
1
1
ESLS
TSER
0
0
1.
E3
RFLX
TSER
0
0
1.
E5
EFLX
TSER
0
0
1.
E5
RZFX
TSER
0
0
1.
E5
186
***
PRZM
3.1
Input
Data
File;
ORAPPLEX.
INP;
Modified
April
5,
1998
***
***
Modified
for
Carbaryl
by
Laurence
Libelo,
6/
21/
00
***
***
Use
rate
changed
to
QUA
(July
21,
1998
QUA
Report)
AVERAGE
VALUES
on
2/
23/
01
***
***
Crops
simulated:
Apples,
Crabapples,
and
Quince
***
***
Location
Washington
County,
Oregon;
Meadow/
Orchard
Scenario;
MLRA:
A2
***
***
Manning's
N:
Assume
sparse
grass
under
mature
trees
(ca.
20
feet)
***
***
Temperature
data
read
***
***
This
file
is
for
scenario
standardization;
Reference
chemical
is
Atrazine
***
***
See
ORAPPLEX.
wpd
for
scenario
details
***
Carbaryl
Cornelius
silt
loam,
15%
slope,
Hydrologic
Group:
C
0.740
0.150
2
17.000
1
3
9.2
10.3
11.8
13.6
15.30
15.3
14.2
12.5
10.9
9.4
8.6
9.1
4
0.43
3.30
1.0
10.0
5.4
2
15.00
354.0
1
1
0.25
17.0
100.000
3
91
71
71
0.0
600
1
3
0103
0105
0112
0.01
0.01
0.01
0.015
0.015
0.015
36
010448
150548
151248
1
010449
150549
151249
1
010450
150550
151250
1
010451
150551
151251
1
010452
150552
151252
1
010453
150553
151253
1
010454
150554
151254
1
010455
150555
151255
1
010456
150556
151256
1
010457
150557
151257
1
010458
150558
151258
1
010459
150559
151259
1
010460
150560
151260
1
010461
150561
151261
1
010462
150562
151262
1
010463
150563
151263
1
010464
150564
151264
1
010465
150565
151265
1
010466
150566
151266
1
010467
150567
151267
1
010468
150568
151268
1
010469
150569
151269
1
010470
150570
151270
1
010471
150571
151271
1
010472
150572
151272
1
010473
150573
151273
1
010474
150574
151274
1
010475
150575
151275
1
010476
150576
151276
1
010477
150577
151277
1
010478
150578
151278
1
010479
150579
151279
1
010480
150580
151280
1
010481
150581
151281
1
010482
150582
151282
1
010483
150583
151283
1
The
label
max
used
(5
apps
of
2
lb
a.
i./
acre
(3.3
kg/
ha))
***
Aerial
Application:
,
Aerial
@
95%
eff.
w/
5%
drift
180
1
0
0
Chemical
Kd:
3.0
(silt
Loam
soil);
AeSM:
T1/
2:
12
days;
AnSM:
T1/
2
=
24
days
***
Record
16:
Application
information;
set
specific
to
carbaryl
***
300448
0
2
0.00
2.24
0.95
0.05
140548
0
2
0.00
2.24
0.95
0.05
280548
0
2
0.00
2.24
0.95
0.05
110648
0
2
0.00
2.24
0.95
0.05
250648
0
2
0.00
2.24
0.95
0.05
300449
0
2
0.00
2.24
0.95
0.05
140549
0
2
0.00
2.24
0.95
0.05
280549
0
2
0.00
2.24
0.95
0.05
110649
0
2
0.00
2.24
0.95
0.05
250649
0
2
0.00
2.24
0.95
0.05
300450
0
2
0.00
2.24
0.95
0.05
140550
0
2
0.00
2.24
0.95
0.05
187
280550
0
2
0.00
2.24
0.95
0.05
110650
0
2
0.00
2.24
0.95
0.05
250650
0
2
0.00
2.24
0.95
0.05
300451
0
2
0.00
2.24
0.95
0.05
140551
0
2
0.00
2.24
0.95
0.05
280551
0
2
0.00
2.24
0.95
0.05
110651
0
2
0.00
2.24
0.95
0.05
250651
0
2
0.00
2.24
0.95
0.05
300452
0
2
0.00
2.24
0.95
0.05
140552
0
2
0.00
2.24
0.95
0.05
280552
0
2
0.00
2.24
0.95
0.05
110652
0
2
0.00
2.24
0.95
0.05
250652
0
2
0.00
2.24
0.95
0.05
300453
0
2
0.00
2.24
0.95
0.05
140553
0
2
0.00
2.24
0.95
0.05
280553
0
2
0.00
2.24
0.95
0.05
110653
0
2
0.00
2.24
0.95
0.05
250653
0
2
0.00
2.24
0.95
0.05
300454
0
2
0.00
2.24
0.95
0.05
140554
0
2
0.00
2.24
0.95
0.05
280554
0
2
0.00
2.24
0.95
0.05
110654
0
2
0.00
2.24
0.95
0.05
250654
0
2
0.00
2.24
0.95
0.05
300455
0
2
0.00
2.24
0.95
0.05
140555
0
2
0.00
2.24
0.95
0.05
280555
0
2
0.00
2.24
0.95
0.05
110655
0
2
0.00
2.24
0.95
0.05
250655
0
2
0.00
2.24
0.95
0.05
300456
0
2
0.00
2.24
0.95
0.05
140556
0
2
0.00
2.24
0.95
0.05
280556
0
2
0.00
2.24
0.95
0.05
110656
0
2
0.00
2.24
0.95
0.05
250656
0
2
0.00
2.24
0.95
0.05
300457
0
2
0.00
2.24
0.95
0.05
140557
0
2
0.00
2.24
0.95
0.05
280557
0
2
0.00
2.24
0.95
0.05
110657
0
2
0.00
2.24
0.95
0.05
250657
0
2
0.00
2.24
0.95
0.05
300458
0
2
0.00
2.24
0.95
0.05
140558
0
2
0.00
2.24
0.95
0.05
280558
0
2
0.00
2.24
0.95
0.05
110658
0
2
0.00
2.24
0.95
0.05
250658
0
2
0.00
2.24
0.95
0.05
300459
0
2
0.00
2.24
0.95
0.05
140559
0
2
0.00
2.24
0.95
0.05
280559
0
2
0.00
2.24
0.95
0.05
110659
0
2
0.00
2.24
0.95
0.05
250659
0
2
0.00
2.24
0.95
0.05
300460
0
2
0.00
2.24
0.95
0.05
140560
0
2
0.00
2.24
0.95
0.05
280560
0
2
0.00
2.24
0.95
0.05
110660
0
2
0.00
2.24
0.95
0.05
250660
0
2
0.00
2.24
0.95
0.05
300461
0
2
0.00
2.24
0.95
0.05
140561
0
2
0.00
2.24
0.95
0.05
280561
0
2
0.00
2.24
0.95
0.05
110661
0
2
0.00
2.24
0.95
0.05
250661
0
2
0.00
2.24
0.95
0.05
300462
0
2
0.00
2.24
0.95
0.05
140562
0
2
0.00
2.24
0.95
0.05
280562
0
2
0.00
2.24
0.95
0.05
110662
0
2
0.00
2.24
0.95
0.05
250662
0
2
0.00
2.24
0.95
0.05
300463
0
2
0.00
2.24
0.95
0.05
140563
0
2
0.00
2.24
0.95
0.05
280563
0
2
0.00
2.24
0.95
0.05
110663
0
2
0.00
2.24
0.95
0.05
250663
0
2
0.00
2.24
0.95
0.05
300464
0
2
0.00
2.24
0.95
0.05
140564
0
2
0.00
2.24
0.95
0.05
280564
0
2
0.00
2.24
0.95
0.05
110664
0
2
0.00
2.24
0.95
0.05
250664
0
2
0.00
2.24
0.95
0.05
300465
0
2
0.00
2.24
0.95
0.05
140565
0
2
0.00
2.24
0.95
0.05
280565
0
2
0.00
2.24
0.95
0.05
188
110665
0
2
0.00
2.24
0.95
0.05
250665
0
2
0.00
2.24
0.95
0.05
300466
0
2
0.00
2.24
0.95
0.05
140566
0
2
0.00
2.24
0.95
0.05
280566
0
2
0.00
2.24
0.95
0.05
110666
0
2
0.00
2.24
0.95
0.05
250666
0
2
0.00
2.24
0.95
0.05
300467
0
2
0.00
2.24
0.95
0.05
140567
0
2
0.00
2.24
0.95
0.05
280567
0
2
0.00
2.24
0.95
0.05
110667
0
2
0.00
2.24
0.95
0.05
250667
0
2
0.00
2.24
0.95
0.05
300468
0
2
0.00
2.24
0.95
0.05
140568
0
2
0.00
2.24
0.95
0.05
280568
0
2
0.00
2.24
0.95
0.05
110668
0
2
0.00
2.24
0.95
0.05
250668
0
2
0.00
2.24
0.95
0.05
300469
0
2
0.00
2.24
0.95
0.05
140569
0
2
0.00
2.24
0.95
0.05
280569
0
2
0.00
2.24
0.95
0.05
110669
0
2
0.00
2.24
0.95
0.05
250669
0
2
0.00
2.24
0.95
0.05
300470
0
2
0.00
2.24
0.95
0.05
140570
0
2
0.00
2.24
0.95
0.05
280570
0
2
0.00
2.24
0.95
0.05
110670
0
2
0.00
2.24
0.95
0.05
250670
0
2
0.00
2.24
0.95
0.05
300471
0
2
0.00
2.24
0.95
0.05
140571
0
2
0.00
2.24
0.95
0.05
280571
0
2
0.00
2.24
0.95
0.05
110671
0
2
0.00
2.24
0.95
0.05
250671
0
2
0.00
2.24
0.95
0.05
300472
0
2
0.00
2.24
0.95
0.05
140572
0
2
0.00
2.24
0.95
0.05
280572
0
2
0.00
2.24
0.95
0.05
110672
0
2
0.00
2.24
0.95
0.05
250672
0
2
0.00
2.24
0.95
0.05
300473
0
2
0.00
2.24
0.95
0.05
140573
0
2
0.00
2.24
0.95
0.05
280573
0
2
0.00
2.24
0.95
0.05
110673
0
2
0.00
2.24
0.95
0.05
250673
0
2
0.00
2.24
0.95
0.05
300474
0
2
0.00
2.24
0.95
0.05
140574
0
2
0.00
2.24
0.95
0.05
280574
0
2
0.00
2.24
0.95
0.05
110674
0
2
0.00
2.24
0.95
0.05
250674
0
2
0.00
2.24
0.95
0.05
300475
0
2
0.00
2.24
0.95
0.05
140575
0
2
0.00
2.24
0.95
0.05
280575
0
2
0.00
2.24
0.95
0.05
110675
0
2
0.00
2.24
0.95
0.05
250675
0
2
0.00
2.24
0.95
0.05
300476
0
2
0.00
2.24
0.95
0.05
140576
0
2
0.00
2.24
0.95
0.05
280576
0
2
0.00
2.24
0.95
0.05
110676
0
2
0.00
2.24
0.95
0.05
250676
0
2
0.00
2.24
0.95
0.05
300477
0
2
0.00
2.24
0.95
0.05
140577
0
2
0.00
2.24
0.95
0.05
280577
0
2
0.00
2.24
0.95
0.05
110677
0
2
0.00
2.24
0.95
0.05
250677
0
2
0.00
2.24
0.95
0.05
300478
0
2
0.00
2.24
0.95
0.05
140578
0
2
0.00
2.24
0.95
0.05
280578
0
2
0.00
2.24
0.95
0.05
110678
0
2
0.00
2.24
0.95
0.05
250678
0
2
0.00
2.24
0.95
0.05
300479
0
2
0.00
2.24
0.95
0.05
140579
0
2
0.00
2.24
0.95
0.05
280579
0
2
0.00
2.24
0.95
0.05
110679
0
2
0.00
2.24
0.95
0.05
250679
0
2
0.00
2.24
0.95
0.05
300480
0
2
0.00
2.24
0.95
0.05
140580
0
2
0.00
2.24
0.95
0.05
280580
0
2
0.00
2.24
0.95
0.05
110680
0
2
0.00
2.24
0.95
0.05
250680
0
2
0.00
2.24
0.95
0.05
300481
0
2
0.00
2.24
0.95
0.05
189
140581
0
2
0.00
2.24
0.95
0.05
280581
0
2
0.00
2.24
0.95
0.05
110681
0
2
0.00
2.24
0.95
0.05
250681
0
2
0.00
2.24
0.95
0.05
300482
0
2
0.00
2.24
0.95
0.05
140582
0
2
0.00
2.24
0.95
0.05
280582
0
2
0.00
2.24
0.95
0.05
110682
0
2
0.00
2.24
0.95
0.05
250682
0
2
0.00
2.24
0.95
0.05
300483
0
2
0.00
2.24
0.95
0.05
140583
0
2
0.00
2.24
0.95
0.05
280583
0
2
0.00
2.24
0.95
0.05
110683
0
2
0.00
2.24
0.95
0.05
250683
0
2
0.00
2.24
0.95
0.05
***
Record
17:
Filtra.,
disposit.
foliar
pest.
after
harvest,
and
plant
uptake
***
0.0
3
0.0
***
Record
18:
Foliar
dissipation
parameters
***
0.0
0.0
0.50
Cornelius
silt
loam,
15%
slope,
Hydrologic
Group:
C
148.0
0
0
0
0
0
0
0
0
0
***
Record
26:
Soil
volatilization
constants
***
0.0
0.0
0.0
***
Record
33
***
5
***
Record
34
***
1
15.0
1.30
0.329
0.0
0.0
0.0
***
Record
36:
Soil
half
life
rate
constants;
repeat
for
each
horizon
***
0.058
0.058
0.0
***
Record
37:
***
0.1
0.329
0.099
2.30
3.0
***
Record
39:
Omitted;
parent/
daughter
transformation
rates
***
2
13.0
1.38
0.338
0.0
0.0
0.0
0.029
0.029
0.0
1.0
0.338
0.108
1.11
3.0
3
15.0
1.58
0.340
0.0
0.0
0.0
0.029
0.029
0.0
1.0
0.340
0.110
0.21
3.0
4
55.0
1.52
0.358
0.0
0.0
0.0
0.029
0.029
0.0
5.0
0.358
0.148
0.145
3.0
5
50.0
1.46
0.202
0.0
0.0
0.0
0.029
0.029
0.0
5.0
0.202
0.142
0.07
3.0
0
YEAR
5
YEAR
5
YEAR
5
1
1
1
6
YEAR
PRCP
TSER
0
0
RUNF
TSER
0
0
ESLS
TSER
0
0
1.0E3
RFLX
TSER
0
0
1.0E5
EFLX
TSER
0
0
1.0E5
RZFX
TSER
0
0
1.0E5
190
***
PRZM2
Version
3.12
Input
Data
File
***
***
MNSUGAR1.
inp
Index
Reservoir
Scenario
created
on
12/
13/
99
***
***
Modified
for
CABRBARYL
6/
21/
00
by
Laurence
Libelo
***
***
Bearden
soil
is
a
Benchmark
soil
with
ca.
800K
mapped
acres
in
MLRA
56
***
***
Sugar
beets,
conventional
tillage
***
***
Highest
acreage
sugarbeet
state
is
MN;
highest
county
in
MN
is
Polk
***
***
Manning's
N
value
set
to
0.02
for
residues
applied
to
fallow
surfaces
***
***
Application
timing
information
provided
by
Russ
Severson
(?),
***
University
of
Minnesota
Agricultural
Extension
Service,
Polk
County,
MN,
***
(218)
281
8696
***
PCA
for
sugarbeets
not
available,
use
default
PCA
of
0.87
***
Chemical:
Carbaryl
Bearden
Silty
Clay
Loam;
HYGP:
C;
MLRA
F
56,
Polk
County,
Minnesota
0.760
0.500
0
12.00
1
3
4
0.28
0.12
0.50
10
3
3.00
354.0
1
1
0.10
20.00
80.00
3
91
82
91
0.00
100.00
1
3
0101
1605
1110
0.43
0.18
0.43
0.02
0.02
0.02
36
160548
061048
161048
1
160549
061049
161049
1
160550
061050
161050
1
160551
061051
161051
1
160552
061052
161052
1
160553
061053
161053
1
160554
061054
161054
1
160555
061055
161055
1
160556
061056
161056
1
160557
061057
161057
1
160558
061058
161058
1
160559
061059
161059
1
160560
061060
161060
1
160561
061061
161061
1
160562
061062
161062
1
160563
061063
161063
1
160564
061064
161064
1
160565
061065
161065
1
160566
061066
161066
1
160567
061067
161067
1
160568
061068
161068
1
160569
061069
161069
1
160570
061070
161070
1
160571
061071
161071
1
160572
061072
161072
1
160573
061073
161073
1
160574
061074
161074
1
160575
061075
161075
1
160576
061076
161076
1
160577
061077
161077
1
160578
061078
161078
1
160579
061079
161079
1
160580
061080
161080
1
160581
061081
161081
1
160582
061082
161082
1
160583
061083
161083
1
Application
Schedule:
2
aerial
app
@
1.5
lb
a.
i./
acre
(1.68
kg/
ha,
95%
app.
eff,
16%
spray
drift
72
1
0
0
Carbaryl:
Kd:
3.0;
AeSM:
T1/
2
=
12
days;
AnSM:
T1/
2
=
24
days
300448
0
2
0.00
1.68
0.95
0.16
140548
0
2
0.00
1.68
0.95
0.16
300449
0
2
0.00
1.68
0.95
0.16
140549
0
2
0.00
1.68
0.95
0.16
300450
0
2
0.00
1.68
0.95
0.16
140550
0
2
0.00
1.68
0.95
0.16
300451
0
2
0.00
1.68
0.95
0.16
140551
0
2
0.00
1.68
0.95
0.16
300452
0
2
0.00
1.68
0.95
0.16
140552
0
2
0.00
1.68
0.95
0.16
300453
0
2
0.00
1.68
0.95
0.16
140553
0
2
0.00
1.68
0.95
0.16
300454
0
2
0.00
1.68
0.95
0.16
140554
0
2
0.00
1.68
0.95
0.16
191
300455
0
2
0.00
1.68
0.95
0.16
140555
0
2
0.00
1.68
0.95
0.16
300456
0
2
0.00
1.68
0.95
0.16
140556
0
2
0.00
1.68
0.95
0.16
300457
0
2
0.00
1.68
0.95
0.16
140557
0
2
0.00
1.68
0.95
0.16
300458
0
2
0.00
1.68
0.95
0.16
140558
0
2
0.00
1.68
0.95
0.16
300459
0
2
0.00
1.68
0.95
0.16
140559
0
2
0.00
1.68
0.95
0.16
300460
0
2
0.00
1.68
0.95
0.16
140560
0
2
0.00
1.68
0.95
0.16
300461
0
2
0.00
1.68
0.95
0.16
140561
0
2
0.00
1.68
0.95
0.16
300462
0
2
0.00
1.68
0.95
0.16
140562
0
2
0.00
1.68
0.95
0.16
300463
0
2
0.00
1.68
0.95
0.16
140563
0
2
0.00
1.68
0.95
0.16
300464
0
2
0.00
1.68
0.95
0.16
140564
0
2
0.00
1.68
0.95
0.16
300465
0
2
0.00
1.68
0.95
0.16
140565
0
2
0.00
1.68
0.95
0.16
300466
0
2
0.00
1.68
0.95
0.16
140566
0
2
0.00
1.68
0.95
0.16
300467
0
2
0.00
1.68
0.95
0.16
140567
0
2
0.00
1.68
0.95
0.16
300468
0
2
0.00
1.68
0.95
0.16
140568
0
2
0.00
1.68
0.95
0.16
300469
0
2
0.00
1.68
0.95
0.16
140569
0
2
0.00
1.68
0.95
0.16
300470
0
2
0.00
1.68
0.95
0.16
140570
0
2
0.00
1.68
0.95
0.16
300471
0
2
0.00
1.68
0.95
0.16
140571
0
2
0.00
1.68
0.95
0.16
300472
0
2
0.00
1.68
0.95
0.16
140572
0
2
0.00
1.68
0.95
0.16
300473
0
2
0.00
1.68
0.95
0.16
140573
0
2
0.00
1.68
0.95
0.16
300474
0
2
0.00
1.68
0.95
0.16
140574
0
2
0.00
1.68
0.95
0.16
300475
0
2
0.00
1.68
0.95
0.16
140575
0
2
0.00
1.68
0.95
0.16
300476
0
2
0.00
1.68
0.95
0.16
140576
0
2
0.00
1.68
0.95
0.16
300477
0
2
0.00
1.68
0.95
0.16
140577
0
2
0.00
1.68
0.95
0.16
300478
0
2
0.00
1.68
0.95
0.16
140578
0
2
0.00
1.68
0.95
0.16
300479
0
2
0.00
1.68
0.95
0.16
140579
0
2
0.00
1.68
0.95
0.16
300480
0
2
0.00
1.68
0.95
0.16
140580
0
2
0.00
1.68
0.95
0.16
300481
0
2
0.00
1.68
0.95
0.16
140581
0
2
0.00
1.68
0.95
0.16
300482
0
2
0.00
1.68
0.95
0.16
140582
0
2
0.00
1.68
0.95
0.16
300483
0
2
0.00
1.68
0.95
0.16
140583
0
2
0.00
1.68
0.95
0.16
0.0
3
0.00
0.0
0.00
0.50
Bearden
Silty
Clay
Loam;
Hydrologic
Group
C;
100.00
0
0
0
0
0
0
0
0
0
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
4
1
10.00
1.400
0.377
0.000
0.000
0.58
0.58
0.00
0.10
0.377
0.207
1.160
3.0
2
8.00
1.400
0.377
0.000
0.000
0.029
0.029
0.00
1.00
0.377
0.207
1.160
3.0
3
54.00
1.500
0.292
0.000
0.000
0.029
0.029
0.00
2.00
0.292
0.132
1.160
3.0
4
28.00
1.800
0.285
0.000
0.000
0.029
0.029
0.00
2.0
0.285
0.125
0.174
3.0
192
0
YEAR
5
YEAR
5
YEAR
5
1
1
1
1
YEAR
***
PRCP
TSER
0
0***
RUNF
TCUM
0
0
***
ESLS
TSER
0
0
1.0E3***
***
RFLX
TSER
0
0
1.0E5***
***
EFLX
TSER
0
0
1.0E5***
***
RZFX
TSER
0
0
1.0E5***
193
PRZM3
Input
File,
flcit.
inp
(Jan
28
2000)
***
original
file
source
unknown
***
***
Source
of
crop
and
soil
data
unknown
***
***
modified
for
carbaryl
by
Laurence
Libelo,
6/
21/
00
***
***
modifified
for
Standard
Pond
7/
17/
2000
***
***
Use
rate
changed
to
QUA
(July
21,
1998
QUA
Report)
AVERAGE
VALUES
on
2/
23/
01
***
Location:
Osceola
County,
FL.;
Crop:
citrus;
MLRA
156A
0.77
0.15
0
25.00
1
1
4
0.10
0.13
1.00
10.0
3
1.00
354.0
1
1
0.10
100.00
80.00
3
94
84
89
0.00
100.00
1
3
0101
21
9
2209
0.10
0.10
0.10
.023
.023
.023
36
110548
170748
10848
1
110549
170749
10849
1
110550
170750
10850
1
110551
170751
10851
1
110552
170752
10852
1
110553
170753
10853
1
110554
170754
10854
1
110555
170755
10855
1
110556
170756
10856
1
110557
170757
10857
1
110558
170758
10858
1
110559
170759
10859
1
110560
170760
10860
1
110561
170761
10861
1
110562
170762
10862
1
110563
170763
10863
1
110564
170764
10864
1
110565
170765
10865
1
110566
170766
10866
1
110567
170767
10867
1
110568
170768
10868
1
110569
170769
10869
1
110570
170770
10870
1
110571
170771
10871
1
110572
170772
10872
1
110573
170773
10873
1
110574
170774
10874
1
110575
170775
10875
1
110576
170776
10876
1
110577
170777
10877
1
110578
170778
10878
1
110579
170779
10879
1
110580
170780
10880
1
110581
170781
10881
1
110582
170782
10882
1
110583
170783
10883
1
Application
at
"average"
value
from
QUA
(July
21,
1998
QUA
Report)
2
apps
/
3.4
lb
a.
i.
per
app
***
Application:
4
aerial
appls
@
5
lb
a.
i./
ac/
year
(5.6
kg/
ha)
@95%
eff,
w/
5%
drift
72
1
0
0
CARBARYL
on
FL
Cirtus
300448
0
2
0.00
3.81
0.95
0.05
140548
0
2
0.00
3.81
0.95
0.05
300449
0
2
0.00
3.81
0.95
0.05
140549
0
2
0.00
3.81
0.95
0.05
300450
0
2
0.00
3.81
0.95
0.05
140550
0
2
0.00
3.81
0.95
0.05
300451
0
2
0.00
3.81
0.95
0.05
140551
0
2
0.00
3.81
0.95
0.05
300452
0
2
0.00
3.81
0.95
0.05
140552
0
2
0.00
3.81
0.95
0.05
300453
0
2
0.00
3.81
0.95
0.05
140553
0
2
0.00
3.81
0.95
0.05
300454
0
2
0.00
3.81
0.95
0.05
140554
0
2
0.00
3.81
0.95
0.05
300455
0
2
0.00
3.81
0.95
0.05
140555
0
2
0.00
3.81
0.95
0.05
300456
0
2
0.00
3.81
0.95
0.05
140556
0
2
0.00
3.81
0.95
0.05
300457
0
2
0.00
3.81
0.95
0.05
194
140557
0
2
0.00
3.81
0.95
0.05
300458
0
2
0.00
3.81
0.95
0.05
140558
0
2
0.00
3.81
0.95
0.05
300459
0
2
0.00
3.81
0.95
0.05
140559
0
2
0.00
3.81
0.95
0.05
300460
0
2
0.00
3.81
0.95
0.05
140560
0
2
0.00
3.81
0.95
0.05
300461
0
2
0.00
3.81
0.95
0.05
140561
0
2
0.00
3.81
0.95
0.05
300462
0
2
0.00
3.81
0.95
0.05
140562
0
2
0.00
3.81
0.95
0.05
300463
0
2
0.00
3.81
0.95
0.05
140563
0
2
0.00
3.81
0.95
0.05
300464
0
2
0.00
3.81
0.95
0.05
140564
0
2
0.00
3.81
0.95
0.05
300465
0
2
0.00
3.81
0.95
0.05
140565
0
2
0.00
3.81
0.95
0.05
300466
0
2
0.00
3.81
0.95
0.05
140566
0
2
0.00
3.81
0.95
0.05
300467
0
2
0.00
3.81
0.95
0.05
140567
0
2
0.00
3.81
0.95
0.05
300468
0
2
0.00
3.81
0.95
0.05
140568
0
2
0.00
3.81
0.95
0.05
300469
0
2
0.00
3.81
0.95
0.05
140569
0
2
0.00
3.81
0.95
0.05
300470
0
2
0.00
3.81
0.95
0.05
140570
0
2
0.00
3.81
0.95
0.05
300471
0
2
0.00
3.81
0.95
0.05
140571
0
2
0.00
3.81
0.95
0.05
300472
0
2
0.00
3.81
0.95
0.05
140572
0
2
0.00
3.81
0.95
0.05
300473
0
2
0.00
3.81
0.95
0.05
140573
0
2
0.00
3.81
0.95
0.05
300474
0
2
0.00
3.81
0.95
0.05
140574
0
2
0.00
3.81
0.95
0.05
300475
0
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Soil
Series:
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E0
195
| epa | 2024-06-07T20:31:42.354964 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0012/content.txt"
} |
EPA-HQ-OPP-2002-0138-0013 | Supporting & Related Material | "2002-07-31T04:00:00" | null | Page
1
of
8
U.
S.
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
DC
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
PC
Code
No.
129106
DP
Barcode:
D279109
SUBJECT:
EFED
Review
of
Documents
Relative
to
Section
24c
Special
Local
Needs
Registration
of
Carbaryl
for
Use
on
Oyster
Beds.
TO:
Anthony
Britten,
Chemical
Review
Manager
Betty
Shackleford,
Product
Manager
Special
Review
and
Reregistration
Division
FROM:
Thomas
M.
Steeger,
Ph.
D.,
Senior
Biologist
Environmental
Risk
Branch
IV/
EFED
(7507C)
Through:
Betsy
Behl,
Branch
Chief
Environmental
Risk
Branch
IV/
EFED
(7507C)
The
Environmental
Fate
and
Effects
Division
(EFED)
has
completed
its
review
of
the
materials
submitted
relative
to
the
Section
24c
Special
Local
Needs
registration
of
carbaryl
for
use
on
oyster
beds
in
Willapa
Bay
and
Grays
Harbor,
Washington,
to
control
ghost
shrimp
(Callianassa
californiensis)
and
mud
shrimp
(Upogebia
pugettensis).
The
documents
included
1)
a
report
on
concentrations
of
carbaryl
and
its
degradate
(1
naphthol)
in
marine
sediments
from
sites
treated
with
or
adjacent
areas
treated
with
Sevin
(Stonic
1999);
2)
a
fact
sheet
on
chemicals
of
special
concern
in
Washington
State;
3)
a
memo
from
the
State
of
Washington's
Department
of
Ecology's
review
of
data
relevant
to
the
environmental
effects
of
applying
Sevin
™
to
control
burrowing
shrimp
in
Willapa
Bay
and
Grays
Harbor
oyster
beds;
4)
a
copy
of
the
memorandum
of
agreement
between
the
Washington
State
Department
of
Ecology,
the
Willapa/
Grays
Harbor
Oyster
Growers'
Association
and
other
state
government
and
private
organizations;
and
5)
a
Washington
State
Department
of
Ecology
publication
entitled
Carbaryl
Concentrations
in
Willapa
Bay
and
Recommendations
for
Water
Quality
Guidelines
(Johnson
2001).
Except
for
more
recent
studies
conducted
by
Washington
State
University
and
the
Washington
Department
of
Ecology,
much
of
the
older
(pre
1996)
data
had
procedural
problems
that
limited
the
utility
of
the
data.
The
more
recent
data
indicate
that
carbaryl
residues
in
the
water
column
were
generally
at
or
below
an
effect
threshold
of
0.1
ug/
L
Although
large
carbaryl
applications
can
affect
water
quality
in
areas
distant
from
spray
sites,
the
Washington
Department
of
Ecology
concluded
that
"no
widespread
effects
from
carbaryl
would
be
expected
in
Wallapa
Bay
after
the
end
of
the
[carbaryl]
application
period."
Carbaryl
has
been
used
on
approximately
600
acres
of
Willapa
Bay
and
200
acres
of
Grays
Harbor
at
a
rate
of
7.5
to
10
lbs/
acre/
year
since
the
1960's.
Carbaryl
is
applied
as
a
wettable
powder
Page
2
of
8
to
tidelands
at
low
low
[Spring]
tide
primarily
by
helicopter;
however,
hand
spraying
is
used
in
some
instances.
The
label
restricts
aerial
applications
within
200
feet
of
a
channel
or
slough;
hand
spraying
is
prohibited
within
50
feet
of
a
channel
or
slough.
The
data
collected
and/
or
reviewed
by
the
Washington
Department
of
Ecology
indicate
that
carbaryl
residues
drop
below
the
level
of
quantitation
(<
0.004
ug/
L)
approximately
6
weeks
after
application.
While
concentrations
in
nontarget
areas
immediately
following
the
carbaryl
application
period
are
likely
to
inflict
mortality
to
aquatic
organisms,
no
data
are
provided
to
demonstrate
that
threatened
and/
or
endangered
species
(e.
g.
salmonids)
are
adversely
affected
by
the
treatments
to
oyster
beds.
While
these
documents
provide
additional
information
on
the
environmental
fate
and
effects
of
carbaryl
in
estuarine/
marine
environments,
EFED's
review
of
Washington's
Section
24c
petition
was
based
on
the
required
guideline
fate
and
effects
data
provided
by
the
registrant
in
support
of
the
reregistration
of
carbaryl.
Although
the
EFED
reregistration
eligibility
document
(RED)
for
carbaryl
does
not
estimate
environmental
concentrations
for
applications
directly
to
tidelands
for
control
of
burrowing
shrimp
in
oyster
culture,
it
does
discuss
the
use.
Data
submitted
in
support
of
reregistration
(MRID
419826
06)
indicate
that
estuarine/
marine
invertebrates
will
likely
be
impacted
by
this
route
of
exposure
and
that
certain
species,
e.
g.,
Dungenese
crab
(Cancer
magister),
may
experience
100%
mortality
in
the
application
area.
However,
the
assessment
goes
on
to
note
that
effects
on
aquatic
invertebrates
will
likely
be
temporary
as
most
populations
show
signs
of
recovery
within
2
months.
Additionally,
the
chapter
suggests
that
carbaryl
applications
that
reduce
the
potential
for
drift
to
nontarget
sites,
such
as
direct
injection
of
carbaryl
into
the
sediment,
may
help
mitigate
nontarget
effects.
Review
of
Submitted
Literature
1)
Screening
Survey
of
Carbaryl
(Sevin)
and
1
naphthol
Concentrations
in
Willapa
Bay
Sediments
The
study
was
undertaken
to
determine
the
long
term
persistence
of
carbaryl
and
1
naphthol;
more
specifically,
the
study
objectives
were
to:
°
Determine
if
there
are
residues
of
carbaryl
and
its
degradate
1
naphthol
in
the
marine
sediments
at
historically
sprayed
sites
and
unsprayed
adjacent
sites
°
Monitor
the
depletion
of
these
compounds
in
sediments
following
applications
of
Seven
™
.
°
Measure
concentrations
of
carbaryl
in
centrifuged
sediment
pore
water.
°
Determine
drift
potential.
The
study
was
divided
into
two
phases,
pre
spray
and
post
spray.
Sampling
was
conducted
in
Willapa
Bay
in
areas
deemed
to
be
conducive
to
carbaryl
persistence.
Thus,
areas
with
muddy
and/
or
fine
sediments
were
selected
since
they
were
believed
to
be
more
likely
to
retain
both
carbaryl
and
1
naphthol.
Sandy
sediments
were
not
believed
to
provide
sufficient
clay
or
organic
material
with
which
carbaryl
and/
or
its
degradate
could
sorb.
Page
3
of
8
0
500
1000
1500
2000
2500
3000
3500
010
2030
40
50
60
Days
after
Treatment
Carbaryl
(ppb)
Figure
1
Average
carbaryl
concentrations
in
sediment
collected
from
Willapa
Bay
at
2,
30
and
60
days
after
treatment.
Pre
spray
samples
were
collected
from
areas
that
had
been
sprayed
in
previous
years
or
were
adjacent
to
areas
that
had
been
sprayed
in
previously.
A
reference
site,
Nemah
Oyster
Reserve,
was
sampled
as
an
area
that
had
never
been
sprayed.
Post
spray
samples
were
collected
immediately
following
carbaryl
treatment
and
also
included
areas
adjacent
to
spray
sites.
Treated
sites
included
areas
that
had
been
sprayed
in
years
past
in
addition
to
the
recent
treatment.
Sampling
was
typically
conducted
2,
30
and
60
days
after
treatment
(DAT).
Sediment
samples
were
collected
using
a
stainless
steel
17
cm
diameter
device
that
allowed
sediment
samples
to
be
stratified
into
0
2
cm,
2
7.5
cm,
and
7.5
15
cm
depths.
Total
organic
carbon
(TOC)
and
sediment
size
were
also
analyzed.
Carbaryl
and
1
naphthol
residues
were
measured
both
in
whole
sediment
and
in
centrifuged
pore
water.
Quality
assurance
spiked
sediment
samples
suggest
considerable
amount
of
variability
in
recovery
of
standards.
The
results
may
be
negatively
biased.
Based
on
the
pre
spray
study
results,
all
of
the
historically
sprayed
sites,
adjacent
unsprayed
sites
and
the
reference
site
showed
no
carbaryl
or
1
naphthol
residues
above
the
detection
limit
range
of
21
to
58
ppb.
One
sample
representing
the
shallowest
area
adjacent
to
historically
sprayed
beds
had
trace
(29
ppb)
residues
of
carbaryl.
Post
spray
study
results
indicate
that
carbaryl
concentrations
at
sprayed
sites
ranged
from
2,000
to
3,400
ppb
by
2
DAT,
180
to
220
ppb
by
30
DAT,
and
86
120
ppb
by
60
DAT
(Figure
1).
Although,
adjacent
sites
contained
as
much
as
2,000
ppb
2
DAT,
residues
in
sediment
at
all
adjacent
sites
at
60
DAT
were
close
to
detection
limits
and
ranged
from
27
to
32
ppb.
Residues
for
the
1
naphthol
ranged
from
detection
limits
to
as
high
as
170
ppb
at
2
DAT
and
by
30
DAT
all
samples
had
dropped
to
detection
limits
(22
to
33
ppb);
one
sample
at
60
DAT
contained
naphthol
at
34
ppb.
The
report
concluded
that
once
carbaryl
degrades
to
1
naphthol,
the
degradate
appears
to
readily
leave
the
sediment.
It
did
not
however,
allow
for
the
fact
that
the
degradate
could
have
been
present
in
deeper
reaches
of
the
sediment.
At
adjacent
sites,
1
naphthol
ranged
as
high
as
120
ppb
2
DAT
and
then
dropped
to
below
detection
limits
for
the
remaining
sample
periods.
Carbaryl
residues
in
pore
water
were
only
detected
60
DAT
and
ranged
from
0.57
to
1.15
ppb.
It
is
difficult
to
understand
though
how
the
limit
of
detection
for
pore
water
was
so
much
lower
than
that
for
sediment.
Carbaryl
was
only
detected
in
one
sediment
pore
water
sample
collected
from
an
adjacent
site;
the
residue
was
close
to
the
limit
of
detection
at
0.05
ppb.
Page
4
of
8
Analyses
of
sediment
grain
size
and
total
organic
carbon
revealed
that
the
clay
silt
fraction
of
the
post
spray
sites
ranged
from
25%
to
73%
while
TOC
ranged
from
0.58%
to
2.07%.
Grain
size
and
TOC
were
strongly
correlated
(Pearson
R
2
range
0.89
0.96);
however,
there
was
no
correlation
between
carbaryl
residues
and
TOC.
The
study
concludes
that
carbaryl
is
clearly
persistent
in
treatment
areas
with
residues
being
detected
up
to
60
DAT.
Additionally,
residues
in
sites
adjacent
to
treated
areas
indicate
that
drift
does
occur.
Drift
to
nontarget
sites
was
attributed
to
wind,
depth
of
water
sampled,
and
both
surface
and
bottom
water
currents.
Additionally,
sediment
pore
water
concentrations
exceeded
the
National
Academy
of
Sciences
and
Engineering
water
quality
recommendation
for
carbaryl
of
0.06
ppb.
Additionally,
historic
sampling
revealed
that
water
column
concentrations
prior
to
application
ranged
as
high
as
9.2
ppb.
The
report
notes
that
QA/
QC
standards
suggested
that
actual
pore
water
concentrations
may
be
higher
than
those
reported.
It
is
uncertain
how
much
naphthol
was
present
in
the
water
column;
however,
given
that
naphthol
is
more
toxic
than
the
parent,
the
potential
affect
of
the
residues
on
aquatic
animals
is
a
legitimate
concern.
Finally
the
report
compares
the
sediment
residue
data
to
available
toxicity
data
on
carbaryl
and
concludes
that
Dungeness
crab
larvae
exposed
to
carbaryl
at
concentrations
ranging
from
0.1
to
10
ppb
for
25
days
exhibited
both
molting
effects
and
mortality.
Although
no
formal
data
were
provided
on
the
numbers
of
organisms
affected;
the
author
reports
that
marine
fish
and
invertebrate
mortality
was
observed
2
DAT.
The
author
proposes
that
the
incidental
kills
could
serve
as
forage
for
other
fish
and
foraging
birds
that
would
then
bioaccumulate
carbaryl
in
their
tissues.
The
report
further
suggests
that
indirect
effects,
such
as
endocrine
disruption
and
mutagenicity,
are
not
sufficiently
characterized
and
that
coupled
with
direct
effects
and
the
potential
for
bioaccumulation
in
the
food
chain,
carbaryl
and
1
naphthol
have
the
potential
to
impact
threatend
and/
or
endangered
salmon
stocks.
The
study
would
have
been
more
thorough
had
water
column
concentrations
of
carbaryl
been
measured.
Given
that
the
compound
was
applied
using
both
aerial
and
hand
held
sprayers,
it
is
difficult
to
assess
the
affect
of
drift
relative
to
application
method.
It
would
have
also
been
helpful
to
know
how
representative
the
areas
sampled
were
of
the
total
areas
treated
in
terms
of
TOC
and
grain
size.
Additionally,
the
limit
of
detection
(25
35
ppb)
was
not
sufficiently
low
to
document
residues
in
sediment
and
pore
water
that
may
have
been
sufficiently
high
to
effect
benthic
invertebrates.
2)
Chemicals
of
Special
Concern
in
Washington
State
Report
published
by
the
Washington
Department
of
Ecology
provides
a
brief
overview
of
the
environmental
fate
and
effects
of
carbaryl.
Although
the
overview
has
footnote
numbers,
no
references
were
provided;
therefore,
data
supporting
carbaryl's
characterization
could
not
be
verified.
The
report
implies
that
carbaryl
is
relatively
persistent
and
that
recoveries
of
aquatic
systems
exposed
to
carbaryl
have
taken
as
long
as
3
years.
According
to
the
overview,
carbaryl
is
teratogenic,
immunosuppressive,
and
degrades
to
carcinogenic
compounds.
Page
5
of
8
3)
Washington
Department
of
Ecology
Review
of
Data
Relevant
to
the
Envrionmental
Effects
of
Applying
Carbaryl
to
Control
Burrowing
Shrimp
in
Willapa
Bay
and
Grays
Harbor
Oyster
Beds
(1987).
The
object
of
the
Washington
Department
of
Ecology
review
was
to
answer
the
following
questions:
°
How
long
do
carbaryl
and
its
primary
hydrolysis
product
1
naphthol
persist
in
the
water
column?
°
What
concentrations
of
carbaryl
and
1
naphthol
in
water
are
toxic
to
marine
organisms?
°
How
long
do
carbaryl
and
1
naphthol
persist
in
the
sediments?
°
What
concentrations
of
carbaryl
and
1
naphthol
in
sediment
are
toxic
to
marine
organisms?
°
What
are
the
effects
on
abundance
and
diversity
of
infauna?
°
What
are
the
effects
on
abundance
and
diversity
of
epifauna?
°
What
mortality
is
experienced
by
Dungenees
crab
and
how
does
this
affect
the
fishery?
°
What
mortality
is
experienced
by
fish?
°
Are
birds
adversely
affected?
°
What
are
the
potential
ecological
impacts
of
Sevin
applications?
While
the
environmental
fate
studies
on
water
column
and
sediment
concentrations
during
and
after
application
of
carbaryl
showed
a
decline
in
carbaryl
and
1
naphthol
concentrations,
much
of
the
data
were
discounted
due
to
poor
detection
limits
and
procedural
deficiencies.
Open
literature
reviews
of
ecological
effects
revealed
that
carbaryl
is
more
toxic
to
crustaceans
than
to
molluscs
or
fish;
however,
the
degradate
1
naphthol
is
less
toxic
to
crustaceans
than
carbaryl
but
more
toxic
than
the
parent
to
molluscs
and
fish.
Subacute
effects
of
carbaryl
were
reported
at
concentrations
below
the
detection
limit
(1
mg/
L)
of
most
of
the
monitoring
studies
reported;
the
report
states
that
circumstantial
evidence
suggests
the
potential
for
toxic
effects
at
or
below
0.1
mg/
L
in
sediment.
Sublethal
effects
included
reduced
development
of
oysters
and
delayed
molting
of
crab
larvae,
malformations
in
fish
eggs
and
adults.
Toxicity
of
carbaryl
is
reported
to
increase
with
temperature.
Although
the
report
fails
to
conclusively
resolve
whether
carbaryl
and
its
1
naphthol
degradate
are
sufficiently
persistent
to
effect
aquatic
life,
it
notes
that
the
target
population
of
burrowing
shrimp
take
a
number
of
years
to
recover.
However,
failure
of
a
treated
area
to
recover
may
be
due
to
a
number
of
factors
and
may
not
result
exclusively
on
the
toxicity
of
carbaryl
or
its
degradate.
Page
6
of
8
0
100
200
300
400
500
600
1976
1978
1980
1982
1984
1986
1988
Year
Acres
Treated
Figure
2.
Number
of
acres
treated
with
carbaryl
in
Willapa
Bay
over
years.
0
10000
20000
30000
40000
50000
60000
0
100
200
300
400
500
600
Number
of
AcresTreated
Number
of
Crabs
Killed
Figure
3.
Number
of
crabs
killed
versus
number
of
acres
treated
with
carbaryl
in
Willapa
Bay.
Fisheries
data
collected
on
Willapa
Bay
from
1977
to
1986
show
(Figure
2)
that
the
number
of
acres
treated
with
carbaryl
increased
each
year.
And
that
the
number
of
crabs
killed
by
carbaryl
treatment
also
increased
(Figure
3)
as
the
number
of
acres
treated
increased.
The
number
of
crabs
killed
was
significantly
correlated
(Pearson
Correlation
coefficient
=
0.72;
p
>
rho
=
0.0187)
with
the
number
of
acres
treated.
Over
the
observation
period
an
average
of
53
crabs
(standard
error
=
13)
were
killed
per
acre.
Follow70000
up
studies
by
the
University
of
Washington
that
[Dungeness]
crab
in
treated
areas
are
impacted
but
that
further
studies
are
required
to
establish
population
level
effects
in
Willapa
Bay.
Mortalities
to
fish
were
limited
to
small
specimens
which
were
entrapped
in
shallow
pools
by
the
outgoing
tide
and
directly
exposed
to
carbaryl
during
treatment;
however,
the
reviewed
literature
did
not
address
the
potential
for
indirect
mortality.
Althoughno
studieswereconducted,the
reportconcludedthatlikelihood
ofacuteorchronic
effects
of
carbaryl
on
birds
was
remote.
Whether
there
are
broad
ecological
impacts
associated
with
the
use
of
carbaryl
to
control
burrowing
shrimp
in
Willapa
Bay
remains
an
uncertainty.
The
Environmental
Impact
Statement
concluded
that
the
use
of
carbaryl
by
the
commercial
oyster
industry
was
not
expected
to
cause
significant
impacts
on
the
estuarine
ecosystem
when
applied
at
current
levels.
It
based
this
conclusion
on
the
fact
that:
°
Carbaryl
is
not
accumulated
by
any
food
chain
component
or
transmitted
to
higher
levels
in
the
food
chain.
°
No
chemically
active
radical
group
remains
to
contaminate
the
estuarine
environment.
°
Only
a
small
percentage
of
the
total
intertidal
lands
are
treated
annually;
0.8%
in
Willapa
Bay
and
0.3%
in
Grays
Harbor.
Page
7
of
8
The
report
recommends
though
that
further
work
be
conducted
to
evaluate
the
persistence
of
carbaryl
and
1
naphthol
in
sediment
and
to
better
document
the
effects
of
nontarget
mortality.
4)
Burrowing
Shrimp
Integrated
Pest
Management
Memorandum
of
Agreement
The
memorandum
of
agreement
(MOA)
was
established
between
the
Washington
State
Department
of
Ecology,
Washington
State
Department
of
Agriculture,
the
Washington
State
Commission
on
Pesticide
Registration,
the
Washington
Department
of
Fish
and
Wildlife,
the
Willapa/
Grays
Harbor
Oyster
Growers
Association,
the
Pacific
Coast
Shellfish
Growers
Association
and
the
Pacific
Shellfish
Institute.
The
agreement
acknowledges
that
while
carbaryl
and
its
1
naphthol
degradate
affect
nontarget
species,
are
likely
transported
several
hundred
yards
offsite
by
tidal
action,
and
may
persist
for
several
weeks
in
the
water
column
and
sediments
within
Willapa
Bay/
Grays
Harbor,
treatment
for
burrowing
shrimp
is
necessary
if
economic
losses
due
to
diminished
oyster
harvests
are
to
be
avoided.
The
agreement
acknowledges
that
additional
data
on
the
environmental
fate
and
effects
of
carbaryl
are
necessary
and
that
alternative
methods
of
control
should
be
explored
to
mitigate
adverse
effects
especially
on
threatened/
endangered
salmonids.
The
MOA
establishes
a
process
and
time
for
the
development
of
a
"sustainable
site
specific,
environmentally
sound
and
ecologically
based
[integrated]
pest
management
plan
for
the
control
of
burrowing."
The
MOA
outlines
criteria
to
be
met,
i.
e.,
demonstration
that
burrowing
shrimp
populations
have
reached
a
size
sufficient
to
inflict
economic
losses,
before
which
carbaryl
can
be
applied.
5)
Carbaryl
Concentrations
in
Willapa
Bay
and
Recommendations
for
Water
Quality
Guidelines.
In
the
summer
of
2000,
the
Washington
State
Department
of
Ecology
initiated
a
study
of
Willapa
Bay.
The
study
was
a
follow
up
on
the
Stonic
(1999)
study
from
1996
to
1997
and
concern
that
carbaryl
persisted
at
a
level
of
0.7
ug/
L.
The
objectives
of
the
study
were
to:
°
determine
if
there
is
a
carbaryl
background
that
persists
in
Willapa
Bay
water
outside
the
July
to
August
spray
period;
°
analyzie
carbaryl
in
other
potential
sources
to
Willapa
Bay;
°
achieve
quantitation
limits
for
carbaryl
sufficiently
low
to
evaluate
the
potential
for
causing
toxicity
to
sensitive
marine
organisms;
°
review
the
literature
on
carbaryl's
effects
on
marine
organisms
and
evaluate
appropriate
water
quality
guidelines
for
carbaryl
in
Willapa
Bay.
Results
from
the
study
show
that
carbaryl
was
frequently
detected
in
Willapa
Bay
up
to
4
days
after
application
to
oyster
beds
and
that
carbaryl
was
transported
several
miles
from
the
site
of
application.
However,
the
study
showed
no
evidence
of
carbaryl
background
in
the
Willapa
Bay
water
column.
Additionally,
tributaries
and
cranberry
bog
drainages
were
not
significant
carbaryl
sources.
Carbaryl
had
dropped
to
levels
below
quantitation
(0.004
ug/
L)
approximately
1
month
after
application
Page
8
of
8
Based
on
a
review
of
toxicity
data
on
35
marine
species,
the
report
recommended
0.06
ug/
L
as
a
probable
safe
level
for
marine
organisms
and
a
range
of
0.1
to
0.7
ug/
L
as
a
potential
effects
threshold.
The
value
of
0.06
ug/
L
was
based
on
a
National
Academy
of
Science
approach
using
an
EC50
of
6
ug/
L
for
inhibiting
molting
in
Dungeness
crab
larvae
divided
by
a
100X
safety
factor.
The
data
collected
from
open
literature
suggests
that
carbaryl
is
more
toxic
to
crustaceans
and
echinoderms
than
to
fish,
molluscs,
or
polychaetes.
The
study
notes
that
while
similar
information
was
not
collected
on
the
1
naphthol
degradate,
one
study
has
shown
it
to
be
roughly
twice
as
toxic
to
fish
as
the
parent
compound
but
less
toxic
to
crustaceans.
Carbaryl
was
detected
at
concentrations
within
the
proposed
potential
effects
threshold
several
miles
from
treatment
areas
up
to
several
days
following
application.
The
report
recommended
that
future
water
quality
monitoring
focus
on
the
period
during
or
immediately
after
carbaryl
applications
and
that
data
are
collected
on
carbaryl's
1
naphthol
transformation
product.
Additionally,
the
report
recommends
that
future
effects
testing
include
more
sensitive
test
species
and
indigenous
aquatic
species
that
serve
as
prey
for
endangered/
threatened
species
References
Stonic,
Cynthia.
1999.
Screening
Survey
of
Carbaryl
(Sevin
™
)
and
1
naphthol
Concentrations
in
Willapa
Bay
Sediments.
Washington
State
Department
of
Ecology.
Publication
No.
99
323.
Johnson,
Art.
2001.
Carbaryl
Concentrations
in
Willapa
Bay
and
Recommendations
for
Water
Quality
Guidelines.
Washington
State
Department
of
Ecology.
Environmental
Assessment
Program.
Publication
No.
01
03
005.
| epa | 2024-06-07T20:31:42.415376 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0013/content.txt"
} |
EPA-HQ-OPP-2002-0138-0014 | Supporting & Related Material | "2002-07-31T04:00:00" | null | Page
1
of
5
U.
S.
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
DC
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
PC
Code
No.
129106
DP
Barcode:
D283014
SUBJECT:
EFED
Review
of
Relyea
Paper
Entitled
"Predator
induced
stress
makes
the
pesticide
carbaryl
more
deadly
to
gray
treefrog
tadpoles
(Hyla
versicolor)
"
TO:
Anthony
Britten,
Chemical
Review
Manager
Betty
Shackleford,
Product
Manager
Special
Review
and
Reregistration
Division
FROM:
Thomas
M.
Steeger,
Ph.
D.,
Senior
Biologist
Environmental
Risk
Branch
IV/
EFED
(7507C)
Through:
Betsy
Behl,
Branch
Chief
Environmental
Risk
Branch
IV/
EFED
(7507C)
The
Environmental
Fate
and
Effects
Division
(EFED)
has
completed
its
review
of
the
research
article
entitled
"Predator
induced
stress
makes
the
pesticide
carbaryl
more
deadly
to
gray
treefrog
tadpoles
(Hyla
versicolor)"
published
in
the
February
2001
issue
of
the
Proceedings
of
the
National
Academy
of
Science.
The
paper,
authored
by
Rick
Relyea
and
Nathan
Mills
(Department
of
Biology,
University
of
Pittsburg)
provides
data
demonstrating
that
prolonged
sub
acute
exposure
of
gray
treefrog
tadpoles
to
carbaryl
at
3
to
4%
of
the
reported
LC50
(2.5
20.6
mg/
L)
killed
10
to
60%
of
the
tadpoles.
Furthermore,
the
paper
claims
that
in
the
presence
of
"predatory
cues"
carbaryl
was
2
to
4
times
more
lethal
to
tadpoles.
The
authors
conclude
that
"under
more
realistic
conditions
of
increased
exposure
times
and
predatory
stress
[simulated
in
their
study],
current
application
rates
for
carbaryl
can
potentially
devastate
gray
treefrog
populations"
and
that
given
the
common
mechanism
of
action,
i.
e.,
acetylcholinesterase
inhibition,
of
carbaryl
with
other
widely
used
pesticides
(carbamates
and
organophosphates),
the
"negative
impacts
may
be
widespread
in
nature."
While
EFED
concurs
that
biotic
and
abiotic
effects
do
impact
the
toxicity
of
chemicals,
we
do
not
concur
with
the
author's
contention
that
their
protocol
is
indicative
of
"more
realistic
ecological
conditions"
than
EFED's
current
battery
of
acute
and
chronic
toxicity
tests;
all
of
these
studies
are
conducted
under
rigidly
controlled
laboratory
conditions
and
are
not
intended
to
be
representative
of
all
of
the
variables
that
may
affect
the
toxicity
of
a
compound
in
the
field.
Furthermore,
the
EFED
environmental
fate
and
ecological
risk
assessment
chapter
on
carbaryl
submitted
in
support
of
the
re
registration
eligibility
decision
does
attempt
to
account
for
carbaryl's
risk
to
amphibians
and
is
to
some
extent
protective
to
amphibians
at
the
concentrations
discussed
Page
2
of
5
in
the
Relyea
and
Mills
paper.
However,
while
the
authors
are
correct
that
a
cumulative
assessment
of
the
effects
of
all
chemicals
acting
through
a
similar
mode
of
action
may
be
more
realistic,
the
logistics
of
conducting
such
an
evaluation
would
require
additional
resources
than
are
currently
available
in
EFED.
The
EFED
environmental
fate
and
ecological
risk
assessment
chapter
on
carbaryl
contains
both
acute
and
chronic
amphibian
toxicity
data
(see
Attachment
1
for
excerpt
on
amphibians
from
chapter).
Although
bullfrogs
(Rana
catesbeiana)
are
relatively
inured
(LD50
>
4,000
mg/
Kg)
to
carbaryl
on
an
acute
oral
exposure
basis,
leopard
frog
tadpoles
(Rana
blairi)
exhibited
a
90%
reduction
in
swimming
activity
at
carbaryl
concentrations
in
the
3.5
7.2
mg/
L
range.
The
chapter
notes
that
such
an
impairment
would
likely
render
the
tadpoles
[prey]
vulnerable
to
predation
provided
the
predators
were
not
similarly
impaired.
Furthermore,
the
chapter
notes
that
chronic
exposure
of
southern
leopard
frogs
(Rana
sphenocephala)
to
carbaryl
led
to
developmental
and
growth
effects
and
that
the
long
term
effects
of
short
term
carbaryl
exposures
to
amphibians
during
critical
life
stages
was
uncertain
and
could
potentially
lead
to
population
level
effects.
Therefore,
the
EFED
risk
assessment
does
discuss
qualitatively
the
potential
susceptibility
of
amphibians
following
both
acute
and
chronic
exposure
to
carbaryl.
EFED
does
not
typically
evaluate
risk
to
aquatic
animals
on
a
species
by
species
or
class
byclass
basis
but
rather
relies
on
surrogate
species
as
representatives
of
broad
ranges
of
aquatic
organisms.
As
with
most
screening
level
risk
assessments
conducted
by
EFED,
the
carbaryl
chapter
used
fish
toxicity
data
as
a
surrogate
for
amphibians.
Toxicity
values
for
freshwater
fish
ranged
from
0.25
to
20
mg/
L;
the
most
sensitive
species,
i.
e.,
Atlantic
salmon
(Salmo
salar)
with
a
96
hour
LC50
value
of
0.25
mg/
L,
was
selected
for
calculating
risk
quotient
(RQ)
values
used
in
EFED's
assessment
of
ecological
risk
to
freshwater
vertebrates.
The
salmon
LC50
value
represents
roughly
10%
of
the
lower
LC50
range
(2.5
to
20.6
mg/
L)
for
amphibians
reported
in
Relyea
and
Mills
paper.
Given
that
EFED's
levels
of
concern
(LOC),
i.
e.,
the
ratio
of
expected
environmental
concentrations
(EEC)
to
the
LC50
value,
for
endangered
is
0.05,
if
the
EEC
was
greater
than
0.01
mg/
L,
it
would
exceed
EFED's
LOC.
Therefore,
the
ecological
risk
assessment
for
aquatic
vertebrates
is
protective
for
species
with
96
hour
LC50
values
greater
than
0.01
mg/
L.
(0.04%
of
the
range
reported
by
Relyea
and
Mills).
EFED
concurs
with
the
study
authors
that
biotic
and
abiotic
effects
can
impact
the
toxicity
of
pesticides
and
that
it
is
difficult
to
account
for
these
effects
on
the
basis
of
the
limited
laboratory
tests
that
are
typically
available
for
evaluating
the
effects
of
pesticides.
EFED
also
concurs
with
the
authors
that
chemicals
with
similar
modes
of
action
may
have
additive
toxicities
and
that
cummulative
assessments
may
better
account
for
toxicity;
however,
the
practicality
of
implementing
such
evaluations
is
limited
for
screening
level
assessments.
EFED
is
uncertain
regarding
how
representative
the
Relyea
and
Mills
article
is
of
field
effects
though
or
of
the
direct
effects
of
carbaryl
and
predatory
cues.
The
experimental
design
included
10
tadpoles
in
10
liter
polyethylene
tubs
containing
filtered
tapwater.
In
a
10
day
static
renewal
study,
they
changed
water
on
days
3
and
7.
In
16
day
static
renewal
exposures,
they
changed
water
every
4
days.
Water
quality
parameters
(dissolved
oxygen,
temperature,
pH
and
Page
3
of
5
ammonia)
were
measured
midway
through
the
16
day
exposure
studies.
Predator
treatments
consisted
of
a
larval
salamander
(Ambystoma
maculatum)
housed
within
a
250
ml
plastic
cup,
covered
with
a
fiberglass
window
screening,
in
each
of
the
exposure
tanks;
controls
consisted
of
the
plastic
cup
alone.
Nominal
carbaryl
concentrations
ranged
from
0.045
to
0.54
mg/
L;
both
negative
and
solvent
(acetone)
controls
were
run
concurrently.
The
results
demonstrate
that
increased
ammonia
concentrations
were
associated
(P<
0.0001,
range
of
means
=
0.21
0.99
mg/
L)
with
carbaryl
concentration,
an
effect
attributed
to
the
presence
of
dead
tadpoles
and
excess
unconsumed
food.
A
regression
analysis
of
survival
against
ammonia
was
significant
(P
<
0.001,
but
not
particularly
predictive
(R
2
=
0.395).
Predators
had
no
effect
on
ammonia
(P
>
0.1)
and
only
had
small
effects
on
oxygen
and
pH
(9%
decrease
in
oxygen,
P
<
0.0001;
5%
decrease
in
pH,
P
=
0.019).
Given
that
water
quality
parameters
were
only
measured
midway
through
the
study
and
that
both
tadpoles
and
thus
feeding
rates
were
likely
increasing
throughout
the
study,
ammonia
levels
may
have
been
considerably
higher
toward
the
end
of
the
studies.
Thus
it
is
unclear
whether
ammonia,
pH
and
dissolved
oxygen
had
an
effect
on
the
toxicity
of
carbaryl
to
tadpoles.
It
is
noteworthy
that
the
Relyea
and
Mills
data
showed
precipitous
declines
in
tadpole
survival
after
5
days
of
exposure.
Although
it
is
difficult
to
design
a
study
that
can
accurately
reflect
field
conditions
and
particularly
predator
prey
relationships,
EFED
is
not
convinced
that
the
Relyea
and
Mills
study
could
be
interpreted
as
more
representative
of
field
conditions.
Typically,
prey
demonstrate
predator
avoidance
behavior
in
the
presence
of
a
perceived
threat.
In
this
study,
tadpoles
were
unable
to
escape
their
perceived
threat;
predatory
cues,
i.
e.,
seeing
a
predator
(visual
cues)
may
have
protracted
their
response
well
beyond
the
chemical
cues
released
following
the
salamander's
consumption
of
tadpoles.
It
is
questionable
whether
tadpoles
would
have
remained
in
view
of
a
potential
predator
under
more
realistic
conditions.
In
refined
ecological
assessments,
EFED
oftentimes
has
mesocosm
study
data
available
to
assess
the
risk
of
pesticides
under
"field
conditions".
These
studies,
while
considerably
more
expensive
that
the
Relyea
and
Mills
protocol,
may
represent
the
most
accurate
reflection
of
controlled
field
studies.
It
is
interesting
to
note
though
that
while
mesocosm
studies
may
yield
LC50
values
similar
to
laboratory
studies,
they
rarely
provide
LC50
values
showing
enhanced
toxicity.
Test
species
within
these
studies
are
better
able
to
rely
on
compensatory
mechanism
to
shield
themselves
from
the
toxic
effects
of
chemicals.
In
addition,
the
environmental
fate
of
pesticides
is
often
different
under
field
conditions.
Under
alkaline
conditions,
i.
e.,
pH
>
7,
carbaryl
undergoes
hydrolysis
with
half
lives
ranging
from
0.15
to
12
days.
While
Relyea
and
Mills
accurately
note
carbaryl's
susceptibility
to
hydrolysis,
they
fail
to
mention
that
under
aearobic
conditions,
carbaryl
is
also
microbially
degraded
in
the
aquatic
environment
with
a
half
life
of
approximately
5
days.
It
is
likely
that
gray
treefrogs
in
the
Relyea
and
Mills
study
were
exposed
to
carbaryl
concentrations
considerably
lower
than
nominal
after
3
to
4
days.
Thus
the
actual
exposure
regime
may
have
been
more
representative
of
pulsed
exposures
to
declining
concentrations
of
carbaryl
and
increasing
concentrations
of
ammonia.
While
it
is
clear
that
predators
had
an
effect
on
the
response
of
tadpoles
to
the
exposure
regime,
EFED
does
not
concur
that
the
test
results
are
representative
of
the
effects
of
predation
on
carbaryl
toxicity
alone.
Page
4
of
5
EFED
concurs
with
Relyea
and
Mills
that
both
biotic
and
abiotic
factors
impact
the
toxicity
of
pesticides
and
that
current
screening
methods
do
not
account
for
the
full
range
of
these
effects
nor
do
screening
level
assessments
take
into
account
aggregate
effects
from
exposure
to
chemicals
with
similar
modes
of
action.
Screening
level
assessments
attempt
to
identify
where
EFED's
LOCs
are
exceeded
and
where
EFED
has
uncertainties
regarding
risk.
With
respect
to
amphibians,
the
chapter
discusses
the
likelihood
of
acute
and
chronic
effects
from
current
uses
of
carbaryl.
Page
5
of
5
Attachment
1.
Excerpt
on
Amphibians
from
the
Environmental
Fate
and
Ecological
Risk
Assessment
for
the
Reregistration
of
Carbaryl
Chapter
According
to
an
available
supplemental
study
with
a
50%
carbaryl
formulation,
the
LD50
for
the
bullfrog
(Rana
catesbeiana)
is
greater
than
4,000
mg/
kg,
or
practically
nontoxic
(MRID
00160000).
A
single
acute
exposure
of
plains
leopard
frog
tadpoles
(Rana
blairi)
to
carbaryl
concentrations
in
the
3.5
7.2
mg/
L
range
led
to
a
90%
reduction
in
swimming
activity,
including
sprint
speed
and
sprint
distance,
activity
ceasing
completely
at
7.2
mg/
L
(Bridges
1997).
This
reduction
in
activity
and
swimming
performance
may
result
in
increased
predation
rates
and,
because
activity
is
closely
associated
with
feeding,
may
result
in
slowed
growth
that
could
lead
to
failure
to
complete
metamorphosis.
Acute
exposure
to
low
carbaryl
levels
may
not
only
affect
immediate
survival
of
tadpoles
but
also
impact
critical
life
history
functions.
On
a
chronic
basis,
carbaryl
has
been
shown
to
have
the
potential
to
adversely
affect
amphibians.
In
a
recent
study,
nearly
18%
of
southern
leopard
frog
(Rana
sphenocephala)
tadpoles
exposed
to
carbaryl
during
development
exhibited
some
type
of
developmental
deformity,
including
both
visceral
and
limb
malformations,
compared
to
a
single
deformed
(<
1%)
control
tadpole
demonstrating
that
carbaryl
exposure
can
result
in
amphibian
deformities
(Bridges,
2000).
Although
the
length
of
the
larval
period
was
the
same
for
all
experimental
groups,
tadpoles
exposed
throughout
the
egg
stage
were
smaller
than
their
corresponding
controls.
Because
exposure
to
nonpersistent
chemicals
may
last
for
only
a
short
period
of
time,
it
is
important
to
examine
the
long
term
effects
that
short
term
exposure
has
on
larval
amphibians
and
the
existence
of
any
sensitive
life
stage.
Any
delay
in
metamorphosis
or
decrease
in
size
at
metamorphosis
can
impact
demographic
processes
of
the
population,
potentially
leading
to
declines
or
local
extinction.
| epa | 2024-06-07T20:31:42.419674 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0014/content.txt"
} |
EPA-HQ-OPP-2002-0138-0015 | Supporting & Related Material | "2002-07-31T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
CERTIFIED
MAIL
June
29,
2001
Danielle
LaRochelle
Registration
Product
Manager
Aventis
CropScience
USA
P.
O.
Box
12014
2
T.
W.
Alexander
Drive
Research
Triangle
Park,
NC
27709
Re:
Preliminary
Risk
Assessments
for
Human
Health
and
for
Environmental
Fate
and
Ecological
Effects
for
the
Reregistration
Eligibility
Decision
on
Carbaryl
Dear
Ms.
LaRochelle:
Enclosed
are
the
preliminary
risk
assessments
for
human
health
and
for
environmental
fate
and
ecological
effects
for
the
reregistration
eligibility
decision
for
carbaryl.
This
advance
opportunity
to
review
EPA's
pesticide
risk
assessments
for
errors
is
an
integral
part
of
a
wider
effort
to
involve
the
public
in
implementation
of
the
Food
Quality
Protection
Act
of
1996,
as
described
in
section
VIII
of
the
Federal
Register
notice
published
on
March
15,
2000
(65
FR
14200).
Within
the
next
30
days,
please
identify
and
comment
on
any
errors
in
the
enclosed
preliminary
risk
assessments.
During
this
phase
of
the
reregistration
process,
you
should
only
address
typographic,
mathematical,
or
computational
type
of
errors.
Upon
receipt
of
your
"error
correction"
submission,
the
Agency
will
evaluate
your
comments
and
will
revise
the
preliminary
risk
assessments
as
necessary.
At
this
phase,
EPA
will
not
address
comments
that
concern
matters
of
policy,
interpretation,
or
applicability
of
data.
There
will
be
future
opportunities
to
address
these
type
of
comments
as
part
of
the
public
participation
process.
In
addition,
we
would
like
you
to
review
the
risk
assessment
documents
for
confidential
business
information
(CBI).
Please
inform
the
Agency
in
writing
of
any
claims
of
CBI
contained
in
these
documents.
If
we
do
not
receive
notice
in
writing
of
any
such
claims,
within
30
days
from
the
receipt
of
this
letter,
we
will
assume
the
document
is
free
of
CBI.
Also,
please
inform
EPA
of
any
pertinent
completed,
pending,
or
planned
studies,
and
2
any
other
sources
of
information
you
intend
to
submit
on
carbaryl.
Providing
EPA
with
a
timetable
for
completing
and
submitting
such
information
will
enable
us
to
better
plan
for
refining
the
risk
assessments
and
completing
the
reregistration
and
tolerance
reassessments.
In
September
2001,
EPA
expects
to
release
to
the
public
your
comments
to
both
preliminary
risk
assessments,
the
Agency's
response
to
your
comments,
and
the
revised
human
health
and
environmental
risk
assessments.
These
documents
will
be
placed
in
the
Public
Docket
and/
or
posted
on
EPA's
website
(www.
epa.
gov/
pesticides/
reregistration/
status.
htm).
EPA
will
announce
the
availability
of
these
documents
via
a
Notice
of
Availability
in
the
Federal
Register
and
through
an
electronic
listserver
message.
Please
send
your
response
in
both
printed
and
electronic
form,
within
30
days
of
receipt
of
this
letter,
including
claims
of
CBI,
and
other
requested
information
to
me
at
the
following
address:
Anthony
Britten
US
EPA
(7508C)
1200
Pennsylvania
Avenue,
N.
W.
Washington,
D.
C.
20460
Email
Address:
britten.
anthony@
epa.
gov
If
you
have
any
questions,
please
feel
free
to
contact
me
at
(703)
308
8179
or
by
email.
Sincerely,
Anthony
Britten,
Chemical
Review
Manager
Reregistration
Branch
3
Special
Review
and
Reregistration
Division
2
Enclosures
| epa | 2024-06-07T20:31:42.423865 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0015/content.txt"
} |
EPA-HQ-OPP-2002-0138-0016 | Supporting & Related Material | "2002-07-31T04:00:00" | null | August
8,
2001
Mr.
Anthony
Britten
Special
Review
and
Reregistration
Division
Office
of
Pesticide
Programs
(7508C)
U.
S.
Environmental
Protection
Agency
Room
266A,
Crystal
Mall
2
1921
Jefferson
Davis
Highway
Arlington,
Virginia
22202
Corr.
#
daL075
01
Dear
Mr.
Britten,
Re:
Carbaryl;
Chemical
number
56801;
EPA
Reg.
No.
264
324
Review
of
the
Preliminary
Risk
Assessments
for
Human
Health
and
for
Environmental
Fate
and
Ecological
Effects
for
the
Reregistration
Eligibility
Decision
on
Carbaryl
We
have
completed
our
review
of
the
preliminary
human
health
and
environmental
fate
and
ecological
effects
risk
assessments
for
the
Reregistration
Eligibility
Decision
of
carbaryl.
Our
comments
on
the
Agency's
assessments
are
enclosed
in
the
following
documents:
Review
of
the
Draft
Human
Health
Risk
Assessment
Review
of
the
Draft
Environmental
Fate
and
Ecological
Risk
Assessment
for
the
Reregistration
of
Carbaryl
Hard
copies
of
the
above
documents
will
be
sent
by
express
mail
within
the
next
week.
Key
issues
discussed
in
these
documents
are
as
follow:
DRAFT
HUMAN
HEALTH
RISK
ASSESSMENT
FQPA
Considerations
A
2
Generation
reproduction
study
was
recently
completed
and
submitted
to
the
Agency.
The
No
Observable
Effect
Levels
(NOELs)
for
carbaryl
administered
in
the
diet,
in
CD®
(SD)
rats
under
the
conditions
of
this
study,
were:
°
For
parental
systemic
toxicity:
75
ppm
°
For
parental
reproductive
toxicity:
1500
ppm
°
For
offspring
toxicity:
75
ppm
In
addition,
Aventis
has
submitted
to
the
EPA
a
revised
Developmental
Neurotoxicity
Study
(DNT)
which
demonstrated
that
no
alterations
in
brain
morphometric
measurements
were
observed
in
the
offspring,
thus
no
increased
sensitivity
was
observed
in
the
pups.
Aventis
firmly
believes
that
with
the
submission
of
these
two
studies,
the
data
gap
for
the
2
generation
reproduction
study
is
fulfilled
and
the
issue
with
the
developmental
neurotoxicity
study
is
resolved.
Thus,
the
Agency
has
the
required
data
to
justify
removing
the
extra
10X
FQPA
Safety
Factor
from
the
risk
calculations
throughout
the
Human
Health
Risk
Assessment
for
carbaryl.
Mr.
Anthony
Britten
August
8,
2001
Page
2
Additional
Uncertainty
Factors
For
the
chronic
study
in
dogs,
Aventis
does
not
agree
with
the
additional
3X
for
a
lack
of
a
NOEL
in
the
study.
According
to
the
policy
issued
in
August
2000
concerning
the
endpoint
for
selection
for
cholinesterase
inhibiting
compounds,
the
Agency
stated
that
the
red
blood
cell
(RBC)
inhibition
should
be
used
instead
of
the
plasma.
The
NOEL
for
RBC
cholinesterase
inhibition
was
125
ppm
(3.1
mg/
kg/
day).
Additionally,
Aventis
believes
that
the
brain
cholinesterase
inhibition
observed
at
the
125
ppm
level
was
slightly
above
background
level
and
was
not
of
toxicological
concerns
due
to
the
lack
of
clinical
signs
observed
at
this
dose
level.
Furthermore,
Aventis
performed
a
five
week
study
in
dogs,
which
agreed
with
the
results
of
the
chronic
study.
Therefore,
it
is
our
opinion
that
all
calculations
based
on
the
chronic
dog
in
the
document
should
be
adjusted
to
reflect
the
removal
of
the
3X
safety
factor.
Cancellation
of
Certain
Uses
of
Carbaryl
Use
on
Barley,
Oats,
Rye,
and
Cotton:
Changes
should
be
made
throughout
the
Human
Health
Risk
Assessment
and
associated
supporting
documents
to
reflect
the
cancellation
of
the
use
on
barley,
oats,
rye,
and
cotton.
It
should
be
noted
that
Aventis
CropScience
labels
for
the
technical
materials
and
the
end
use
products
containing
carbaryl
were
amended
to
delete
these
uses.
The
Agency
has
already
approved
the
labeling
changes.
Use
on
Poultry:
Aventis
CropScience
will
no
longer
support
the
use
of
carbaryl
for
direct
application
to
poultry,
as
well
as
the
poultry
quarters
treatment.
We
will
submit
a
request
for
cancellation
of
these
uses
in
accordance
with
section
6(
f)(
1)
of
the
Federal
Insecticide,
Fungicide
and
Rodenticide
Act
(FIFRA).
The
cancellation
of
this
use
causes
a
significant
improvement
in
the
risk
assessment
since
poultry
are
the
major
contributor
to
the
risk
estimate.
We
believe
that
only
the
dietary
analyses
conducted
without
poultry
should
be
included
in
the
HED
Chapter.
Analyses
including
poultry
would
be
unrealistic
and
misleading.
Dietary
Exposure
Assessment
An
industry
sponsored
Carbamate
Market
Basket
Survey
(CMBS)
was
conducted
and
submitted
to
the
Agency
for
use
in
the
dietary
exposure
and
risk
assessment
for
carbaryl.
The
Carbamate
Market
Basket
Survey
Task
Force
met
with
EPA/
HED
before
the
start
of
the
study
to
review
the
purpose
and
design
of
the
study.
The
EPA
assured
the
task
force
that
the
study
data
would
be
used
in
risk
assessments,
taking
precedence
over
all
other
monitoring
or
field
trial
data
available
for
those
crops.
A
surrogation
plan
according
to
HED
SOP
99.3
was
also
assured.
These
data
provide
more
realistic
measures
of
residues
to
which
consumers
are
exposed
and
they
should
be
included
in
the
dietary
analyses
as
agreed
upon
by
the
CMBS
Task
Force
and
the
EPA.
Water
Exposure
Assessment
EPA
has
based
its
assumptions
about
concentrations
of
carbaryl
in
drinking
water
upon
model
simulations.
Aventis
CropScience
conducted
a
drinking
water
monitoring
program
that
provides
the
best
estimate
of
concentrations
of
carbaryl
in
drinking
water.
The
study
uses
the
sampling
design
for
acute
endpoints
recommended
in
industry/
EPA
meetings
during
1999
(weekly
sampling
during
times
of
peak
concentrations
over
a
three
year
period).
Twenty
sites,
representative
of
the
most
vulnerable
community
water
systems
in
the
highest
use
areas
of
carbaryl,
were
selected.
These
included
16
sites
in
agricultural
areas
and
4
locations
in
urban
areas.
Samples
were
collected
from
the
inlet
and
outlet
water
at
each
sampling
interval.
Outlet
samples
were
only
analyzed
when
residues
were
present
in
the
inlet
samples.
The
analytical
method
has
a
limit
of
quantification
of
0.030
ppb
and
a
limit
of
detection
of
0.002
ppb.
The
study
provides
information
on
concentrations
of
carbaryl
in
community
water
systems
most
likely
to
contain
the
highest
concentrations
of
carbaryl.
Residues
of
carbaryl
in
other
areas
would
be
expected
to
be
Mr.
Anthony
Britten
August
8,
2001
Page
3
lower.
The
study
should
be
used
in
the
carbaryl
exposure
calculations
as
it
provides
the
drinking
water
concentrations
needed
for
FQPA
dietary
assessments.
Occupational
and
Residential
Exposure
Assessment
Aventis
CropScience
has
conducted,
or
is
in
the
process
of
conducting,
studies
relevant
to
the
refinement
of
the
occupational
and
residential
risk
assessment.
These
studies
are
as
follows:
Study
Anticipated
Completion
Date
4
Week
Repeated
Dose
Dermal
Toxicity
Study
with
SEVIN
®
XLR
Plus
in
Rats.
September
2001
4
Week
Repeated
Dose
Dermal
Toxicity
Study
with
SEVIN
®
80S
in
Rats.
September
2001
4
Week
Repeated
Dose
Dermal
Toxicity
Study
with
Carbaryl
Technical
in
Rats.
September
2001
Measurement
of
Pesticide
Exposure
of
Suburban
Residents
Associated
with
the
Residential
Use
of
Carbaryl.
March
2002
Biological
monitoring
of
citrus
orchard
application
and
post
application
apple
thinning
and
cherry
harvesting
job
functions
March
2002
DRAFT
ENVIRONMENTAL
FATE
AND
ECOLOGICAL
RISK
ASSESSMENT
Carbaryl
Studies
to
Fulfill
Requirements
Aventis
CropScience
is
in
the
process
of
conducting,
or
has
scheduled,
studies
relevant
to
the
refinement
of
the
environmental
risk
assessments
for
carbaryl
and
the
major
degradate
1
naphthol.
These
studies
are
as
follows:
Rate
and
Route
of
Aerobic
Degradation
in
Soils.
These
studies
have
been
initiated
with
parent
carbaryl
applied
to
four
diverse
U.
S.
soils.
The
data
are
intended
to
provide
additional
half
life
determinations
for
parent
carbaryl
and
the
major
degradate
1
naphthol.
Expected
completion
date:
March
2002
Aerobic
Aquatic
Metabolism
in
Two
Water/
Sediment
Systems.
These
studies
have
been
initiated
with
parent
carbaryl
applied
to
two
distinct
U.
S.
water/
sediment
systems.
The
data
are
intended
to
provide
additional
half
life
determinations
for
parent
carbaryl
and
the
major
degradate
1
naphthol.
In
addition,
further
identification
of
additional
degradation
products
is
anticipated.
Expected
completion
date:
March
2002
Mr.
Anthony
Britten
August
8,
2001
Page
4
Adsorption
and
Desorption
of
1
Napthol
to
five
soils.
This
study
has
been
scheduled
to
evaluate
the
adsorption
and
desorption
of
the
major
carbaryl
degradate
to
five
soils/
sediment.
The
data
are
intended
to
provide
information
necessary
to
evaluate
the
environmental
risks
from
1
naphthol
in
standard
models.
Expected
completion
date:
March
2002
For
the
reregistration
process
in
the
EU,
Aventis
CropScience
is
in
the
process
of
conducting,
or
has
scheduled,
studies
relevant
to
the
refinement
of
the
ecotoxicological
risk
assessments
for
carbaryl
and
the
major
degradate
1
naphthol.
These
studies
are
as
follows:
Studies
with
Carbaryl:
Acute
oral
LD50
in
mallard
ducks
Dynamic
acute
LC50
in
bluegill
sunfish
Acute
toxicity
in
Daphnia
Acute
toxicity
in
Chironomus
riparius
Toxicity
in
Selenastrum
capricornutum
Acute
oral
and
contact
toxicity
in
honeybees
14
d
toxicity
in
earthworms
Effects
on
soil
microorganisms
(nitrification/
carbon
cycle)
Effect
on
sewage
treatment
Studies
with
1
naphthol
Early
life
stage
study
in
fathead
minnows
Acute
toxicity
in
Daphnia
Acute
toxicity
in
Daphnia
in
presence
of
sediment
Chronic
toxicity
in
Daphnia
14
d
toxicity
in
earthworms
Formulated
Product
Vegetative
Vigor
Toxicity
in
Selenastrum
capricornutum
Acute
oral
and
contact
toxicity
in
honeybees
Effect
on
non
target
arthropods
14
d
toxicity
in
earthworms
Effects
on
soil
microorganisms
(nitrification/
carbon
cycle)
Ecotoxicological
Risk
Assessments
Aventis
has
pointed
out
several
errors
in
the
PRZM
input
parameters
(see
comments
made
to
Tables
5
and
6
of
the
draft
RED).
Overly
conservative
estimates
of
foliar
dissipation
half
lives
and
changes
in
ecotoxicology
study
endpoints
would
dictate
a
re
calculation
of
the
EECs
and
risk
quotients
is
warranted
in
a
number
of
instances.
Mr.
Anthony
Britten
August
8,
2001
Page
5
Endocrine
Disruption
Reports
in
the
open
literature
on
the
reproductive
effects
of
carbaryl
in
wild
mammals
are
at
best
ambivalent.
The
recently
submitted
2
generation
study
in
rats
demonstrates
the
absence
of
reproductive
effects.
As
EPA
pointed
out,
findings
reported
in
the
literature
were
made
at
concentrations
well
above
the
highest
peak
concentration
modeled.
Therefore
these
findings
are
irrelevant
for
a
risk
assessment
and
at
the
current
stage
of
discussion
about
endocrine
disruption.
If
the
concern
about
the
endocrine
potential
of
carbaryl
persists,
the
issue
should
be
revisited
once
the
Agency's
endocrine
disrupter
screening
and
testing
program
as
well
as
a
policy
on
how
to
incorporate
positive
findings
into
an
ecological
risk
assessment
have
been
fully
developed.
Mobility
The
classification
of
carbaryl
as
mobile
to
very
mobile
is
inconsistent
with
measured
Koc
values
of
177
to
249
(MRID
43259301).
According
to
the
widely
used
classification
scheme
of
McCall,
et
al.
(1980)
wherein
Koc
values
between
150
and
500
denote
medium
mobility
in
soil,
carbaryl
would
be
classified
as
having
medium
mobility
in
most
soils.
This
classification
of
medium
mobility
is
further
supported
by
the
acceptable
column
leaching
study
(MRID
43320701)
in
which
aged
carbaryl
residues
were
only
slightly
mobile
in
a
number
of
soils.
The
mobility
of
carbaryl
would
be
expected
to
be
higher
in
sandy
soils
or
in
soils
of
low
organic
matter.
1
Napthol
Fate
and
Transport
The
Agency
is
requiring
additional
information
on
the
persistence
and
mobility
of
1
naphthol,
a
major
environmental
degradate
of
carbaryl.
However,
a
half
life
for
1
naphthol
of
less
than
1
day
can
be
calculated
from
the
carbaryl
aerobic
soil
metabolism
study
(MRID
42785101).
The
data
from
this
study
demonstrate
that
under
aerobic
soil
conditions
the
formation
and
decline
of
1
naphthol,
starting
from
parent
carbaryl,
is
complete
in
less
than
14
days.
This
half
life
can
be
used
for
preliminary
environmental
fate
modeling
to
estimate
EECs
for
1
naphthol.
The
EPA
suggested
that
1
naphthol
is
not
strongly
sorbed
to
soil.
Additional
information
available
in
the
literature
demonstrates
that
the
sorption
of
1
naphthol
to
soil
is
stronger
than
that
seen
for
carbaryl
itself.
Hassett
et
al.
(1981)
has
demonstrated
that
the
sorption
of
1
naphthol
was
the
result
of
sorption
to
organic
carbon
resulting
in
Koc
values
between
431
and
15,618.
These
data
indicate
that
1
naphthol
is
less
mobile
and
less
susceptible
to
leaching
than
carbaryl
itself,
and
they
demonstrate
that
at
least
a
portion
of
the
1
naphthol
residue
is
tightly
sorbed
to
soil
constituents.
To
meet
the
requirement
for
information
on
the
adsorption
and
desorption
of
1
naphthol
by
the
Agency,
the
registrant
is
conducting
an
adsorption/
desorption
study
to
meet
the
163
1
guideline.
Study
results
should
be
available
for
submission
to
the
Agency
in
the
first
quarter
of
the
calendar
year
2002.
Ground
Water
EPA
summarized
information
on
the
detection
of
carbaryl
in
groundwater
from
the
EPA
Pesticides
in
Groundwater
Database,
the
EPA
STORET
database
and
the
NAWQA
database.
Each
of
the
databases
shows
a
pattern
of
very
low
levels
of
carbaryl
detection
in
few
groundwater
resources.
These
analyses
confirm
several
statements
made
by
the
Agency
that
carbaryl
have
limited
potential
to
impact
groundwater
resources.
However,
on
page
2
of
the
Memorandum
issued
June
28,
2001,
in
conjunction
with
the
EFED
RED
chapter
for
carbaryl,
EPA
is
requiring
additional
information
on
"Surface
and
groundwater
monitoring
in
urban
and
suburban
use
areas
(non
guideline)."
Based
on
the
characteristics
of
carbaryl
and
the
available
data
demonstrating
limited
impact
of
carbaryl
on
ground
water
resources,
additional
studies
to
evaluate
the
potential
for
carbaryl
to
contaminate
groundwater
are
unnecessary
and
unwarranted.
Mr.
Anthony
Britten
August
8,
2001
Page
6
Please
let
me
know
if
you
need
any
additional
information.
My
phone
number
is
(919)
549
2718.
Sincerely,
Danielle
A.
Larochelle
Danielle
A.
Larochelle
Registration
Manager
1
CARBARYL
Chemical
ID
No.
056801;
Case
0080
Review
of
the
Draft
Human
Health
Risk
Assessment
August
8,
2001
Aventis
CropScience
P.
O.
Box
12014,
2
T.
W.
Alexander
Drive
Research
Triangle
Park,
NC
27709
2
TABLE
OF
CONTENTS
GENERAL
COMMENTS
........................................................................................................
3
FQPA
Considerations
.........................................................................
3
Additional
UncertaintyFactors
...........................................................
3
Cancellation
of
Certain
Uses
of
Carbaryl
...........................................
3
Dietary
Exposure
Assessment
............................................................
4
Water
Exposure
Assessment
..............................................................
4
Occupational
and
Residential
Exposure
Assessment
.........................
4
PART
I
TOXICOLOGY
DATA
BASE
...................................................................................
6
Line
by
Line
Review
of
the
Toxicology
Data
Base
Evaluation
from
the
Human
Health
Risk
Assessment
Document
for
Carbaryl
(June
19,
2001)
........................................................................
6
PART
I
TOXICOLOGY
DATA
BASE
..................................................................................
20
SUPPORTING
DISCUSSIONS
.......................................................
20
PART
II
DIETARY
AND
WATER
EXPOSURE/
RISK
ASSESSMENT
......................................
32
Line
by
Line
Review
of
the
Dietary
and
Water
Exposure
Assessment
of
the
Human
Health
Risk
Assessment
Document
for
Carbaryl
(June
19,
2001)
......................................................................
32
Line
by
Line
Review
of
the
Supporting
Document
"Revised
Dietary
Exposure
Analysis
for
the
HED
Revised
Human
Health
Risk
Assessment
(Felicia
A.
Fort;
April
26,
2001)"
......................
40
PART
II
DIETARY
AND
WATER
EXPOSURE/
RISK
ASSESSMENT
......................................
44
SUPPORTING
DISCUSSIONS
.......................................................
44
PART
III
RESIDUE
CHEMISTRY
CONSIDERATIONS
..........................................................
51
Line
by
Line
Review
of
the
Residue
Chemistry
Information
Included
in
the
Human
Health
Risk
Assessment
Document
for
Carbaryl
(June
19,
2001)
......................................................................
51
Line
by
Line
Review
of
the
Supporting
Document
"Product
and
Residue
Chemistry
Chapters
for
the
Reregistration
Eligibility
Decision
(Felecia
Fort;
November
14,
2000)"
......................
53
Line
by
Line
Review
of
the
Supporting
Document
"Carbaryl:
Occupational
and
Residential
Exposure
Assessment
and
Recommendations
for
the
Reregistration
Eligibility
Decision
Document
(Jeffrey
L.
aDawson;
June
28,
2001)"
..................
59
PART
IV
OCCUPATIONAL
AND
RESIDENTIAL
EXPOSURE/
RISK
ASSESSMENT
...............
64
SUPPORTING
DISCUSSION
.........................................................
64
APPENDIX
I
...................................................................................................................
66
3
General
Comments
FQPA
Considerations
A
2
Generation
reproduction
study
was
recently
completed
and
submitted
to
the
Agency.
The
No
Observable
Effect
Levels
(NOELs)
for
carbaryl
administered
in
the
diet,
in
CD®
(SD)
rats
under
the
conditions
of
this
study,
were:
°
For
parental
systemic
toxicity:
75
ppm
°
For
parental
reproductive
toxicity:
1500
ppm
°
For
offspring
toxicity:
75
ppm
In
addition,
Aventis
has
submitted
to
the
EPA
a
revised
Developmental
Neurotoxicity
Study
(DNT)
which
demonstrated
that
no
alterations
in
brain
morphometric
measurements
were
observed
in
the
offspring,
thus
no
increased
sensitivity
was
observed
in
the
pups.
Aventis
firmly
believes
that
with
the
submission
of
these
two
studies,
the
data
gap
for
the
2
generation
reproduction
study
is
fulfilled
and
the
issue
with
the
developmental
neurotoxicity
study
is
resolved.
Thus,
the
Agency
has
the
required
data
to
justify
removing
the
extra
10X
FQPA
Safety
Factor
from
the
risk
calculations
throughout
the
Human
Health
Risk
Assessment
for
carbaryl.
Additional
UncertaintyFactors
For
the
chronic
study
in
dogs,
Aventis
does
not
agree
with
the
additional
3X
for
a
lack
of
a
NOEL
in
the
study.
According
to
the
policy
issued
in
August
2000
concerning
the
endpoint
for
selection
for
cholinesterase
inhibiting
compound,
the
Agency
stated
that
the
red
blood
cell
(RBC)
should
be
used
instead
of
the
plasma.
The
NOEL
for
RBC
cholinesterase
inhibition
was
125
ppm
(3.1
mg/
kg/
day).
Additionally,
Aventis
believes
that
the
brain
cholinesterase
inhibition
observed
at
the
125
ppm
level
was
slightly
above
background
level
and
was
not
of
toxicological
concerns
due
to
the
lack
of
clinical
signs
observed
at
this
dose
level.
Furthermore,
Aventis
performed
a
five
week
study
in
dogs,
which
agreed
with
the
results
of
the
chronic
study.
Therefore,
it
is
our
opinion
that
all
calculations
based
on
the
chronic
dog
in
the
document
should
be
adjusted
to
reflect
the
removal
of
the
3X
safety
factor.
Cancellation
of
Certain
Uses
of
Carbaryl
Use
on
Barley,
Oats,
Rye,
and
Cotton
Changes
should
be
made
throughout
the
Human
Health
Risk
Assessment
and
associated
supporting
documents
to
reflect
the
cancellation
of
the
use
on
barley,
oats,
rye,
and
cotton.
It
should
be
noted
that
Aventis
CropScience
labels
for
the
technical
materials
and
the
end
use
products
containing
carbaryl
were
amended
to
delete
these
uses.
The
Agency
has
already
approved
the
labeling
changes.
Please
refer
to
Part
III
of
this
document
(Residue
Chemistry
Considerations)
for
current
labeling
information.
Corrections
on
label
acceptance
dates
are
also
provided
in
Part
III.
4
Use
on
Poultry
Aventis
CropScience
will
no
longer
support
the
use
of
carbaryl
for
direct
application
to
poultry,
as
well
as
the
poultry
quarters
treatment.
We
will
submit
a
request
for
cancellation
of
these
uses
in
accordance
with
section
6(
f)(
1)
of
the
Federal
Insecticide,
Fungicide
and
Rodenticide
Act
(FIFRA).
The
cancellation
of
this
use
causes
a
significant
improvement
in
the
risk
assessment
since
poultry
are
the
major
contributor
to
the
risk
estimate.
We
believe
that
only
the
dietary
analyses
conducted
without
poultry
should
be
included
in
the
HED
Chapter.
Analyses
including
poultry
would
be
unrealistic
and
misleading.
Dietary
Exposure
Assessment
An
industry
sponsored
Carbamate
Market
Basket
Survey
(CMBS)
was
conducted
and
submitted
to
the
Agency
for
use
in
the
dietary
exposure
and
risk
assessment
for
carbaryl.
The
Carbamate
Market
Basket
Survey
Task
Force
met
with
EPA/
HED
before
the
start
of
the
study
to
review
the
purpose
and
design
of
the
study.
The
EPA
assured
the
task
force
that
the
study
data
would
be
used
in
risk
assessments,
taking
precedence
over
all
other
monitoring
or
field
trial
data
available
for
those
crops.
A
surrogation
plan
according
to
HED
SOP
99.3
was
also
assured.
These
data
provide
more
realistic
measures
of
residues
to
which
consumers
are
exposed
and
they
should
be
included
in
the
dietary
analyses
as
agreed
upon
by
the
CMBS
Task
Force
and
the
EPA.
Water
Exposure
Assessment
EPA
has
based
its
assumptions
about
concentrations
of
carbaryl
in
drinking
water
upon
model
simulations.
Aventis
CropScience
conducted
a
drinking
water
monitoring
program
that
provides
the
best
estimate
of
concentrations
of
carbaryl
in
drinking
water.
The
study
uses
the
sampling
design
for
acute
endpoints
recommended
in
industry/
EPA
meetings
during
1999
(weekly
sampling
during
times
of
peak
concentrations
over
a
three
year
period).
Twenty
sites,
representative
of
the
most
vulnerable
community
water
systems
in
the
highest
use
areas
of
carbaryl,
were
selected.
These
included
16
sites
in
agricultural
areas
and
4
locations
in
urban
areas.
Samples
were
collected
from
the
inlet
and
outlet
water
at
each
sampling
interval.
Outlet
samples
were
only
analyzed
when
residues
were
present
in
the
inlet
samples.
The
analytical
method
has
a
limit
of
quantification
of
0.030
ppb
and
a
limit
of
detection
of
0.002
ppb.
The
study
provides
information
on
concentrations
of
carbaryl
in
community
water
systems
most
likely
to
contain
the
highest
concentrations
of
carbaryl.
Residues
of
carbaryl
in
other
areas
would
be
expected
to
be
lower.
The
study
should
be
used
in
the
carbaryl
exposure
calculations
as
it
provides
the
drinking
water
concentrations
needed
for
FQPA
dietary
assessments.
Occupational
and
Residential
Exposure
Assessment
Aventis
CropScience
has
conducted,
or
is
in
the
process
of
conducting,
studies
relevant
to
the
refinement
of
the
occupational
and
residential
risk
assessment.
These
studies
are
as
follows:
5
Study
Anticipated
Completion
Date
4
Week
Repeated
Dose
Dermal
Toxicity
Study
with
Sevin
XLR
Plus
in
Rats.
September
2001
4
Week
Repeated
Dose
Dermal
Toxicity
Study
with
Sevin
80S
in
Rats.
September
2001
4
Week
Repeated
Dose
Dermal
Toxicity
Study
with
Carbaryl
Technical
in
Rats.
September
2001
Measurement
of
Pesticide
Exposure
of
Suburban
Residents
Associated
with
the
Residential
Use
of
Carbaryl.
March
2002
Biological
monitoring
of
citrus
orchard
application
and
postapplication
apple
thinning
and
cherry
harvesting
job
functions
March
2002
6
Part
I
Toxicology
Data
Base
Line
by
Line
Review
of
the
Toxicology
Data
Base
Evaluation
from
the
Human
Health
Risk
Assessment
Document
for
Carbaryl
(June
19,
2001)
1.0
Executive
Summary
Section
Number
1.0
Page:
3
Paragraph:
4
Line:
3
EPA
comment:
In
the
developmental
neurotoxicity
study
in
the
rat,
alterations
in
brain
morphometric
measurements
were
observed
in
offspring.
Aventis'
response:
Aventis
has
submitted
to
EPA
a
revised
DNT,
which
demonstrated
no
alterations
in
brain
morphometric
measurements
taken
in
the
offspring,
thus
no
increased
sensitivity
was
observed
in
the
pups.
The
details
of
this
study
will
be
discussed
below
in
the
supporting
`Discussion
Section'.
Page:
3
Paragraph:
5
Line:
3
EPA
comment:
No
acceptable
two
generation
reproduction
study
is
available.
Aventis'
response:
Aventis
has
submitted
to
EPA
a
new
2
Generation
Reproduction
Study
with
carbaryl,
which
neither
demonstrated
that
carbaryl
is
a
reproductive
toxicant
nor
demonstrated
that
the
pups
were
more
sensitive
than
the
dams.
The
NOELs
for
carbaryl
administered
in
the
diet,
in
CD®
(SD)
rats
under
the
conditions
of
this
study
were:
°
For
parental
systemic
toxicity:
75
ppm
°
For
parental
reproductive
toxicity:
1500
ppm
°
For
offspring
toxicity:
75
ppm
The
details
of
this
study
will
be
discussed
below
in
the
supporting
`Discussion
Section'.
Page:
3
continued
on
page
4
Paragraph:
5
Lines:
4
7
EPA
comment:
In
the
developmental
neurotoxicity
study,
maternal
toxicity
was
observed
at
the
same
dose
as
changes
in
brain
morphometric
measurements
in
offspring;
however,
these
brain
measurements
were
not
performed
at
the
next
lower
dose
and
consequently,
there
is
some
uncertainty
about
the
NOAEL
for
this
effect.
7
Aventis'
response:
As
stated
above,
Aventis
has
submitted
to
EPA
a
revised
DNT,
which
demonstrated
no
alterations
in
brain
morphometric
measurements
taken
in
the
offspring,
thus
no
increased
sensitivity
was
observed
in
the
pups.
The
details
of
this
study
will
be
discussed
below
in
the
supporting
`Discussion
Section'.
Page:
4
Paragraph:
5
continuation
from
page
3
Lines:
2
9
EPA
comment:
The
10x
Food
Quality
Protection
Act
(FQPA)
Safety
Factor
has
been
retained
because:
1)
the
toxicology
data
base
is
incomplete;
there
is
a
data
gap
for
the
multi
generation
reproduction
study
in
rats;
2)
an
assessment
of
susceptibility
following
pre/
post
natal
exposure
to
carbaryl
could
not
be
made
due
to
the
data
gap
for
the
reproduction
study;
3)
there
is
concern
for
the
results
of
the
developmental
neurotoxicity
study
(uncertainty
about
NOAEL).
Based
on
these
considerations,
the
10x
safety
factor
was
applied
to
all
population
subgroups
in
assessing
risks
from
acute
and
chronic
dietary
exposures
and
residential
exposures
of
all
durations.
Aventis'
response:
As
stated
above,
Aventis
has
submitted
to
EPA
a
revised
DNT
and
a
new
2
Generation
Reproduction
Study
that
has
a
direct
impact
on
the
FQPA
Safety
Factor.
Aventis
firmly
believes
that
with
the
submission
of
these
two
studies,
the
data
gap
for
the
2
generation
reproduction
study
will
be
fulfilled
and
the
NOEL
question
for
the
DNT
will
be
resolved.
Thus,
the
Agency
has
the
required
data
to
reduce
the
FQPA
Safety
Factor
from
10X
to
1X.
Page:
4
Paragraph:
1
Lines
1
6:
EPA
comment:
Carbaryl
has
been
classified
as
a
Group
C
possible
human
carcinogen
based
on
an
increased
incidence
of
hemangiosarcomas
and
combined
hemangiomas/
hemangiosarcomas
in
CD
1
mice
at
1000
ppm
(146
mg/
kg/
day)
and
above.
Mechanistic
metabolism
studies
and
a
study
in
heterozygous
p53
deficient
mice
were
considered
inadequate
to
demonstrate
a
mode
of
action
for
the
vascular
tumors.
The
default
linear
low
dose
extrapolation
was
used
for
risk
assessment;
the
Q1*
is
1.19
x
10
2
(mg/
kg/
day)
1
based
on
the
mouse
vascular
tumors.
Aventis'
response:
Aventis
strongly
believes
that
the
use
of
carbaryl
products
presents
no
imminent
carcinogenic
risk
to
users
based
on
the
following
points:
Current
data
support
a
hypothesis
that
high
doses
of
carbaryl
in
life
time
studies
produce
tumors
via
a
non
genotoxic
mechanism,
possibly
related
to
altered
metabolism
at
these
high
doses.
8
At
doses
less
than
the
MTD,
there
was
an
increased
incidence
of
tumors
only
in
1
site
of
1
sex
of
1
species.
The
increased
incidence
of
vascular
tumors
in
the
male
mice
after
two
years
of
administration
is
of
questionable
biological
significance.
In
the
p53
knockout
mouse
model,
which
was
demonstrated,
to
be
sensitive
to
the
induction
of
vascular
tumors
by
a
genotoxic
reference
compounds,
carbaryl
was
found
to
be
negative.
The
weight
of
the
evidence
indicates
that
carbaryl
shows
no
potential
for
genotoxicity
Epidemiological
data
on
carbaryl
production
workers
show
no
increase
in
tumor
incidence.
In
the
two
year
bioassay
conducted
in
the
CD1
mouse,
a
statistically
significantly
higher
incidence
of
vascular
tumors
was
noted
in
males
at
1,000
and
8,000
ppm.
In
females,
no
statistically
significant
change
in
the
incidence
of
vascular
tumors
was
observed.
The
overall
incidence
of
vascular
tumors
was
2,
6,
10
and
10
in
males
and
3,
3,
4
and
9
in
females
at
0,
100,
1,000
and
8,000
ppm,
respectively.
In
order
to
address
the
biological
significance
of
the
vascular
tumors,
the
p53
knockout
mouse
model
was
used
as
a
tool
to
study
chemical
carcinogenesis
(Donehower,
1996).
The
p53
mouse
is
a
genetically
manipulated
mouse
in
which
one
allele
of
the
p53
tumor
suppresser
gene
has
been
inactivated.
One
of
the
assumptions
with
the
knockout
model
is
that
a
mutation
at
the
intact
p53
allele
is
necessary
for
the
development
of
the
carcinogenic
process.
In
principle
nongenotoxic
compounds,
which
induce
tumors
by
other
mechanisms
should
not
induce
tumors
in
this
system.
The
p53
knockout
mouse
model
was
validated
by
testing
two
compounds:
urethane,
a
genotoxic
compound
known
to
produce
vascular
tumors
in
standard
carcinogenicity
bioassays,
and
d
limonene,
which
is
neither
genotoxic
nor
carcinogenic
in
mice
but
which
is
known
to
be
carcinogenic
in
the
male
rat
by
a
well
described
non
genotoxic
mechanism.
In
the
validation
study,
the
p53
model
proved
to
be
very
efficient
for
the
induction
of
vascular
tumors
by
genotoxic
compounds
(Bigot,
1999;
Carmichael
et
al.
1999).
Therefore,
this
model
will
produce
an
unambiguous
response
to
specifically
identify
genotoxic
compounds.
Therefore,
carbaryl
was
tested
in
the
p53
mouse.
The
objectives
of
the
studies
were
to
evaluate
if
carbaryl
would
induce
vascular
tumors
in
this
model
and
to
set
a
NOEL
in
this
sensitive
and
specific
model.
Additionally,
this
model
provides
evidence
that
the
tumors
observed
in
the
standard
carcinogenicity
bioassays
resulted
from
an
indirect
genotoxic
effect.
9
Carbaryl
was
administered
continuously
via
the
diet
to
groups
of
20
male
heterozygous
p53
knockout
mice
at
concentrations
of
0,
10,
30
100,
300,
1,000
and
4,000
ppm
for
at
least
180
days.
At
the
end
of
the
study,
all
animals
were
necropsied,
selected
organs
weighed
and
a
range
of
tissues
were
taken,
fixed
and
examined
microscopically.
Carbaryl
did
not
induce
mortalities
or
clinical
signs
related
to
the
treatment.
Only
a
slight
decrease
in
food
consumption
during
the
first
eight
weeks
was
observed
at
4,000
ppm.
This
observation
was
correlated
with
a
lower
body
weight
evolution
in
comparison
with
the
control
animals.
No
tumors
were
found
in
the
4,000
ppm
group.
In
the
other
treated
groups,
a
few
sporadic
tumors
were
found,
but
they
were
clearly
unrelated
to
treatment
and
representative
of
the
spontaneous
tumor
types
present
in
mice
of
this
age
and
strain.
In
particular,
it
should
be
noted
that
no
tumors
were
found
in
the
liver,
kidney
or
vascular
system,
which
were
seen
in
the
original
mouse
oncogenicity
study
with
carbaryl.
The
only
treatment
related
non
proliferative
change
observed
was
the
presence
of
globular
deposits
in
the
umbrella
cell
layer
of
the
urinary
bladder
at
100
ppm
or
more.
In
conclusion,
the
data
from
the
p53
studies,
the
following
conclusion
can
be
made:
1).
The
p53
model
was
validated
with
urethane
one
of
the
few
compound
known
to
induce
specifically
vascular
tumors.
2).
Carbaryl
was
negative,
and
also
did
not
accelerate
the
formation
of
any
other
tumor
types.
3).
There
is
a
clear
NOEL
at
4000
ppm
(approximately
716
mg/
kg
b.
w./
day)
in
the
p53
mouse
study
for
carcinogenicity.
4).
Carbaryl
is
not
a
genotoxic
carcinogen.
Thus
the
weight
of
the
evidence
indicates
that
carbaryl
is
not
a
genotoxic
agent
in
humans.
In
addition,
epidemiological
data
on
carbaryl
production
workers
show
no
increase
in
tumor
incidence.
The
two
epidemiology
studies
of
Aventis
CropScience
(formerly
Rhône
Poulenc
and
Union
Carbide)
factory
workers
representing
a
sub
population
of
the
general
public
with
the
highest
exposure
(i.
e.,
exposure
on
a
daily
basis
over
many
years).
Thus,
the
data
from
these
studies
represent
a
potential
"worst
case"
for
chronic
carbaryl
exposure
to
humans.
The
results
from
these
studies
show
that
the
overall
mortality
experience
of
the
cohort
is
significantly
less
than
expected
when
compared
to
both
United
States
and
West
Virginia
male
death
rates.
In
general,
these
studies
support
conclusion
that
there
were
no
excess
cases
of
cancer
in
this
working
population.
A
further
discussion
of
this
study
and
the
entire
carcinogenicity
issue
will
be
discussed
below
in
the
supporting
`Discussion
Section'.
10
Page:
4
Paragraph:
2
Lines
5
12:
EPA
comment:
The
toxicity
endpoints
selected
for
risk
assessment
are
based
on
neurotoxic
effects
of
ChEI.
The
dose
levels
used
for
the
acute
and
chronic
dietary
risk
assessment,
i.
e.
10
mg/
kg
and
3.1
mg/
kg/
day,
were
both
from
studies
(acute
neurotoxicity
study
in
the
rat
and
chronic
toxicity
study
in
the
dog,
respectively)
in
which
a
NOAEL
was
not
determined.
Therefore,
an
additional
uncertainty
factor
of
3x
was
added
to
the
customary
100x
uncertainty
factor
[10x
for
extrapolation
from
animal
studies
to
humans
and
10x
for
intraspecies
(human)
variation].
The
acute
and
chronic
reference
doses
were
0.03
mg/
kg
and
0.01
mg/
kg/
day,
respectively.
Aventis'
response:
Concerning
the
acute
neurotoxicity
study
in
rats,
Aventis
does
not
disagree
with
the
Agency's
assessment
for
this
endpoint.
However,
for
the
chronic
study
in
dogs,
Aventis
does
not
agree
with
the
additional
3X
for
a
lack
of
a
NOEL
in
the
study.
According
to
the
policy
issued
in
August
2000
concerning
the
endpoint
for
selection
for
cholinesterase
inhibiting
compound,
the
Agency
stated
that
the
red
blood
cell
(RBC)
should
be
used
instead
of
the
plasma.
The
NOEL
for
RBC
cholinesterase
inhibition
was
125
ppm
(3.1
mg/
kg/
day).
Additionally,
Aventis
believes
that
the
brain
cholinesterase
inhibition
observed
at
the
125
ppm
level
are
slightly
above
background
level
and
were
not
of
toxicological
concerns
due
to
the
lack
of
clinical
signs
observed
at
this
dose
level.
Furthermore,
Aventis
performed
a
five
week
study
in
dogs,
which
agreed
with
the
results
of
the
chronic
study.
Therefore,
it
is
our
opinion
that
all
calculations
based
on
the
chronic
dog
in
the
document
should
be
adjusted
to
reflect
the
removal
of
the
3X
safety
factor.
Page:
4
Paragraph:
2
Lines
1
6:
EPA
comment:
No
dermal
or
inhalation
studies
were
available.
Aventis'
response:
As
part
of
the
60
day
public
comment
period,
Aventis
will
be
submitting
three
21
day
dermal
studies,
which
cover
the
technical
material
and
the
formulated
products
SEVIN®
XLR,
and
SEVIN®
80S.
The
study
results
will
not
be
available
in
time
to
provide
the
information
to
the
Agency
as
part
of
the
30
day
comment
period.
Similarly,
Aventis
will
be
submitting
comments
for
the
inhalation
requirement
as
part
of
the
60
day
public
comment
period.
However,
it
should
be
noted
that
in
the
document
titled,
"Carbaryl:
Toxicology
Chapter
For
RED"
the
inhalation
study
was
not
listed
as
a
data
gap
on
page
25
of
that
document.
11
Page:
8
Paragraph:
3
Lines
1
10:
EPA
comment:
HED
calculated
the
risks
of
carbaryl
exposure
in
tobacco.
Based
on
a
pyrolysis
study
submitted
by
the
registrant,
residues
of
carbaryl
total
approximately
44.58
ppm
in
tobacco
smoke
(side
stream
and
main
stream
combined).
Since
this
is
a
composited
sample
of
main
stream
and
side
stream
smoke,
it
greatly
exaggerates
the
actual
exposure
to
the
smoker,
whose
primary
route
of
exposure
is
via
mainstream
smoke.
HED
further
assumed
that
100%
inhaled
is
absorbed
(i.
e.,
that
none
of
the
residue
is
exhaled
along
with
the
smoke).
These
assumptions
result
in
an
extreme
overestimate
of
actual
likely
exposure.
Comparing
exposure
to
the
short
term
inhalation
Lowest
Observable
Adverse
Effects
Level
(LOAEL)
of
10
mg/
kg/
day,
the
short
term
MOE
for
carbaryl
exposure
from
the
use
of
tobacco
is
estimated
to
be
1000
for
males
and
900
for
females.
The
MOEs
are
less
than
the
residential
short
term
inhalation
target
MOE
of
3000
and
therefore,
the
risks
exceed
HED's
level
of
concern
for
the
general
population.
Aventis'
response:
The
relative
risk
of
carbaryl,
which
is
not
a
genotoxic
agent,
as
compared
to
the
many
direct
acting
genotoxic
agents
contained
in
main
and
side
stream
smoke
is
insignificant
and
is
not
calculable.
The
calculation
presented
by
the
Agency
is
crude
at
best
and
does
not
have
any
impact
on
the
relative
risk
of
smoking
cigarettes.
Page:
10
Paragraph:
2
Lines
1
18:
EPA
comment:
HED
evaluated
reports
of
human
carbaryl
poisonings
and
adverse
reactions
associated
with
its
use
from
the
following
sources:
OPP
Incident
Data
System
(IDS);
Poison
Control
Centers'
Toxic
Exposure
Surveillance
System;
California
Department
of
Pesticide
Regulation;
the
National
Pesticide
Telecommunications
Network
(NPTN);
open
literature;
and
an
unpublished
study
submitted
by
the
registrant.
The
data
from
IDS
indicated
that
a
majority
of
cases
from
carbaryl
exposure
involved
dermal
reactions.
A
number
of
other
cases
involved
asthmatics
and
people
who
experienced
hives
and
other
allergic
type
reactions.
It
is
noted
that
the
dermal
sensitization
study
in
the
guinea
pig
was
negative.
Reports
of
allergic
type
reactions
in
humans
could
be
evidence
of
a
difference
in
species
sensitivity
or
could
be
attributable
to
inert
ingredients
in
the
marketed
formulations.
According
to
California
data,
about
half
have
the
cases
involved
skin
and
eye
effects
in
handlers.
About
a
quarter
of
the
skin
reactions
were
due
to
workers
that
were
exposed
to
residues
on
crops.
Reports
from
the
literature
are
very
limited
but
tend
to
support
the
finding
that
carbaryl
has
irritant
properties.
The
Poison
Control
Center
cases
involving
non
occupational
adults
and
older
children
showed
an
increased
risk
in
five
of
the
six
measures
used
for
comparing
carbaryl
incidents
to
all
other
pesticides.
The
carbaryl
cases
were
almost
twice
as
likely
to
require
serious
health
care
(hospitalization
or
treatment
in
a
critical
care
unit)
and
were
two
and
a
half
times
more
likely
to
experience
major
medical
12
outcome
(life
threatening
effects
or
significant
residual
disability)
than
other
pesticides.
This
pattern
of
increased
risk
was
not
seen
among
occupational
reports
or
in
young
children.
This
may
mean
that
careless
handling
by
nonprofessionals
is
a
particular
hazard.
Aventis'
response:
As
stated
by
the
Agency,
reports
from
the
literature
are
very
limited.
To
draw
such
conclusions
that
carbaryl
cases
were
almost
twice
as
likely
to
require
serious
health
care
(hospitalization
or
treatment
in
a
critical
care
unit)
and
were
two
and
a
half
times
more
likely
to
experience
major
medical
outcome
(life
threatening
effects
or
significant
residual
disability)
than
other
pesticides
is
speculative
and
goes
too
far
in
assigning
increased
frequency
values
based
on
limited
and
often
unconfirmed
information.
The
reports
cited
by
the
Agency
from
poison
control
centers
are
difficult
to
interpret
because
the
relative
causative
agent
is
frequently
not
identified.
If
the
agent
is
identified
by
officials,
the
majority
of
the
time
it
is
stated
by
the
officials
that
the
causative
agent
is
merely
speculation
on
their
part
and
that
the
real
agent
is
not
readily
known
with
great
certainty.
According
to
test
conducted
by
Aventis
on
both
technical
grade
and
formulation
products,
carbaryl
is
not
a
skin
sensitizer.
Furthermore,
epidemiological
data
on
carbaryl
production
workers
showed
no
pattern
of
skin
reaction.
This
would
indicate
that
if
the
product
is
used
according
to
the
label,
the
relative
risks
of
skin
reactions
to
carbaryl
are
very
low.
Page:
10
Paragraph:
3
Lines
1
5:
EPA
comment:
Five
case
report
studies
suggested
that
carbaryl
might
be
a
cause
of
chronic
neurological
or
psychological
problems.
Some
of
these
effects
appear
to
be
consistent
with
those
reported
from
organophosphate
poisoning.
However,
unlike
organophosphates,
no
controlled
studies
have
been
undertaken.
If
such
effects
occur
as
a
result
of
over
exposure
to
carbaryl,
they
appear
to
be
relatively
rare.
The
effects
reported
among
the
five
case
reports
are
too
inconsistent
to
draw
any
conclusions,
but
do
suggest
the
need
for
further
study.
Aventis'
response:
Aventis
agrees
with
the
Agency
that
the
five
case
studies
cited
are
weak
at
best
and
that
the
Agency
should
not
be
drawing
any
conclusions
based
on
such
inconsistent
data.
The
discussion
of
such
data
will
lead
the
reader
to
draw
inappropriate
conclusions.
Furthermore,
epidemiological
data
on
carbaryl
production
workers
showed
no
such
pattern
and
would
indicate
that
if
the
product
is
used
according
to
the
label,
the
relative
risks
of
carbaryl
are
very
low.
Page:
11
Paragraph:
1
Lines
1
3:
EPA
comment:
The
epidemiologic
study
submitted
by
the
registrant
compared
mortality
rates
in
plant
workers
exposed
to
carbaryl
to
the
general
population.
HED
concluded
that
13
the
sample
of
workers
was
too
small
and
the
period
of
follow
up
too
short
to
permit
definitive
conclusions.
Aventis'
response:
Aventis
disagrees
with
the
Agency
that
the
mortality
rates
in
plant
workers
exposed
to
carbaryl
cannot
be
translated
to
the
general
population.
The
study
was
statistically
designed
to
specifically
address
this
concern
and
to
examine
other
non
mortality
endpoints.
The
two
epidemiology
studies
of
Aventis
CropScience
(formerly
Rhône
Poulenc)
factory
workers
representing
a
sub
population
of
the
general
public
with
the
highest
exposure
(i.
e.,
exposure
on
a
daily
basis
over
many
years).
Thus,
the
data
from
these
studies
represent
a
potential
"worst
case"
for
chronic
carbaryl
exposure
to
humans.
The
results
from
these
studies
show
that
the
overall
mortality
experience
of
the
cohort
is
significantly
less
than
expected
when
compared
to
both
United
States
and
West
Virginia
male
death
rates.
In
general,
these
studies
support
conclusion
that
there
were
no
excess
cases
of
cancer
in
this
working
population.
Page:
11
Paragraph:
4
Lines
2
4:
EPA
comment:
However,
certain
key
information,
which
would
help
refine
the
risk
assessment,
is
missing.
Toxicology
data
gaps
include
a
reproduction
study,
a
21
day
dermal
study
in
the
rat,
a
90
day
inhalation
study
in
the
rat
and
a
micronucleus
study.
Aventis'
response:
The
Agency
has
previously
granted
a
wavier
for
the
in
vivo
cytogenicity/
micronucleus.
Furthermore,
Aventis
has
fulfilled
the
data
requirement
for
the
in
vivo
mouse
micronucleus
study.
Aventis
believes
that
repeating
the
in
vivo
mouse
micronucleus
study
is
not
appropriate
based
on
the
fact
that
the
top
dose
in
the
currently
submitted
mouse
micronucleus
was
200
mg/
kg/
day
and
was
similar
to
the
mid
dose
of
250
mg/
kg/
day
tested
in
an
acute
gavage
study
in
mice.
At
the
250
mg/
kg
dose
level
tested
in
the
acute
study
plasma,
RBC,
and
brain
cholinesterase
inhibition
was
seen.
The
percent
cholinesterase
inhibition
observed
was
45.7,
45.7,
and
57.8,
respectively.
At
the
highest
dose
tested
(500
mg/
kg)
in
the
acute
study,
percent
cholinesterase
inhibition
for
plasma,
RBC,
and
brain
was
59.8,
57.1,
and
66.6,
respectively.
Additionally,
the
clinical
signs
observed
at
both
the
250
and
500
mg/
kg
dose
levels
were
very
similar
in
both
findings
and
incidences.
Repeating
the
mouse
micronucleus
study
at
a
slightly
higher
dose
level
would
not
result
in
an
increase
in
significant
clinical
signs.
Therefore,
the
base
results
of
the
study
concerning
clastogenic
or
aneugenic
effects
would
not
change.
Carbaryl
is
not
mutagenic
for
these
endpoints.
As
previously
indicated
in
this
document,
Aventis
will
be
submitting
three
21
day
dermal
studies
which
cover
the
technical
material
and
for
the
formulated
products
SEVIN
XLR
and
SEVIN
80S.
Similarly,
Aventis
will
be
submitting
comments
for
the
inhalation
requirement
as
part
of
the
60
day
public
comment
period.
14
However,
it
should
be
noted
that
in
the
document
titled,
"Carbaryl:
Toxiccology
Chapter
For
RED"
the
inhalation
study
was
not
listed
as
a
data
gap
on
page
25
of
that
document.
Section
Number
3.0
Hazard
Profile
Page:
14
15
Paragraph:
1
Lines:
1
10
EPA
comment:
The
Toxicology
Chapter
of
the
RED
was
prepared
by
Dr.
Virginia
Dobozy
(D240992
dated
December
13,
1999).
The
toxicology
database
is
of
good
quality;
however,
it
is
incomplete.
The
following
studies
are
required:
two
generation
reproduction
study,
21
day
dermal
toxicity
study
with
cholinesterase
measurements,
90
day
inhalation
study
with
cholinesterase
measurements
and
micronucleus
study.
The
lack
of
a
reproduction
study
and
some
uncertainty
about
the
findings
in
offspring
in
the
developmental
neurotoxicity
study
are
obstacles
to
assessing
special
sensitivity
of
infants
and
children
and
as
such,
the
10x
FQPA
Safety
Factor
was
retained.
However,
the
database
provides
sufficient
information
for
selecting
toxicity
endpoints
for
risk
assessment
and
therefore,
supports
a
reregistration
eligibility
decision
for
the
currently
registered
uses.
Aventis'
response:
As
stated
previously,
Aventis
has
submitted
to
EPA
a
revised
DNT
and
a
new
2
Generation
Reproduction
Study,
which
have
a
direct
impact
on
the
FQPA
Safety
Factor.
Aventis
firmly
believes
that
with
the
submission
of
these
two
studies,
the
data
gap
for
the
2
generation
reproduction
study
is
fulfilled
and
the
DNT
NOEL
question
will
be
resolved.
Thus,
the
Agency
has
the
required
data
to
reduce
the
FQPA
Safety
Factor
from
10X
to
1X.
As
for
the
21
day
dermal,
90
day
inhalation
and
mouse
micronucleus
studies,
the
need
for
these
studies
is
addressed
in
the
previous
comments
made
by
Aventis.
Page:
17
Paragraph:
1
Lines:
1
6
EPA
comment:
In
the
developmental
neurotoxicity
study,
clinical
signs
of
toxicity
and
plasma
and
brain
ChEI
were
seen
in
maternal
animals
at
the
same
dose
(10
mg/
kg/
day)
as
changes
in
brain
morphometric
measurements
(decreases
in
cerebellar
measurements
in
females
on
Day
11
post
partum)
were
observed
in
offspring;
however,
brain
measurements
were
not
conducted
at
the
next
lower
dose.
The
lowest
NOAEL
after
a
single
dose
administration
in
adult
animals
was
for
maternal
animals
in
the
developmental
neurotoxicity
study,
i.
e.,
1
mg/
kg/
day.
Aventis'
response:
Aventis
has
submitted
to
EPA
a
revised
DNT
Study,
which
demonstrated
that
no
alterations
in
brain
morphometric
measurements
were
observed
in
the
offspring,
thus
no
increased
sensitivity
was
observed
in
the
pups.
The
details
of
this
study
15
will
be
discussed
below
in
the
supporting
`Discussion
Section'.
Page:
17
Paragraph:
2
Lines:
1
3
EPA
comment:
No
subchronic
studies
in
the
rat
or
dog
are
available,
except
for
the
subchronic
neurotoxicity
study
in
rats.
The
chronic
toxicity
data
showed
that,
in
dogs,
decreases
in
plasma,
RBC
and
brain
ChE
were
observed
at
10
mg/
kg/
day;
clinical
signs
of
toxicity
were
also
observed
in
both
sexes.
Aventis'
response:
For
the
chronic
study
in
dogs,
Aventis
does
not
agree
with
the
additional
3X
for
a
lack
of
a
NOEL
in
the
study.
According
to
the
policy
issued
in
August
2000
concerning
the
endpoint
for
selection
for
cholinesterase
inhibiting
compound,
the
Agency
stated
that
the
RBC
should
be
used
instead
of
the
plasma.
The
NOEL
for
RBC
cholinesterase
inhibition
was
125
ppm
(3.1
mg/
kg/
day).
Additionally,
Aventis
believes
that
the
brain
cholinesterase
inhibition
observed
at
the
125
ppm
level
is
slightly
above
background
level
and
was
not
of
toxicological
concerns
due
to
the
lack
of
clinical
signs
observed
at
this
dose
level.
Furthermore,
Aventis
performed
a
five
week
study
in
dogs,
which
agreed
with
the
results
of
the
chronic
study.
Therefore,
it
is
our
opinion
that
all
calculations
based
on
the
chronic
dog
in
the
document
should
be
adjusted
to
reflect
the
removal
of
the
3X
safety
factor.
Page:
17
Paragraph:
3
Lines:
1
21
EPA
comment:
The
Health
Effects
Division's
(HED)
Cancer
Peer
Review
Committee
(CPRC)(
12/
8/
93)
classified
carbaryl
as
a
Group
C
possible
human
carcinogen
based
on
an
increased
incidence
of
hemangiosarcomas
and
combined
hemangiomas/
hemangiosarcomas
in
male
mice.
Both
the
low
dose
extrapolation
(Q1*)
and
margin
of
exposure
(MOE)
approaches
were
proposed
for
risk
assessment.
In
addition,
an
RfD
approach
would
be
provided
to
assess
the
most
sensitive
non
cancer
health
endpoint
for
comparison
to
the
linear
and
MOE
approaches.
The
CPRC
requested
additional
metabolism
studies,
which
could
1)
direct
the
selection
of
the
more
appropriate
quantitative
approach;
and
2)
provide
insight
into
the
significance
of
the
tumors
seen
only
at
excessively
toxic
doses.
Additional
metabolism
studies,
including
mechanistic
studies,
were
submitted
subsequent
to
the
1993
meeting.
A
subgroup
of
the
Cancer
Assessment
Review
Committee
(CARC)
met
on
September
3,
1998,
to
review
the
metabolism
studies
and
concluded
that
the
data
from
all
available
metabolism
studies
were
not
adequate
to
support
a
nonlinear
mode
of
action,
as
described
in
the
1996
EPA
Proposed
Guidelines
for
Carcinogen
Risk
Assessment,
and
therefore
recommended
that
the
default
linear
approach
should
be
used
for
the
cancer
risk
assessment.
The
revised
Q1*,
based
on
the
CD
1
mouse
dietary
study
with
¾
Interspecies
Scaling
Factor,
is
1.19
x
10
2
(mg/
kg/
day)
1
in
human
equivalents.
Subsequently,
the
registrant
submitted
a
special
study
in
genetically
modified
mice.
Carbaryl
was
administered
to
heterozygous
p53
deficient
(knockout)
male
mice
in
the
diet
at
concentrations
of
up
to
4000
ppm
(716.6
mg/
kg/
day)
for
six
16
months.
There
was
no
evidence
of
neoplastic
or
preneoplastic
changes
in
the
vascular
tissues
of
any
organ.
A
model
validation
study
demonstrated
that
vascular
tumors
occur
in
heterozygous
p53
deficient
mice
within
six
months
of
administration
of
a
known
genotoxic
carcinogen
(urethane).
Aventis'
response:
Aventis
strongly
believes
that
the
use
of
carbaryl
products
presents
no
imminent
carcinogenic
risk
to
users
based
on
the
following
points:
Current
data
support
a
hypothesis
that
high
doses
of
carbaryl
in
life
time
studies
produce
tumors
via
a
non
genotoxic
mechanism,
possibly
related
to
altered
metabolism
at
these
high
doses.
At
doses
less
than
the
MTD,
there
was
an
increased
incidence
of
tumors
only
in
1
site
of
1
sex
of
1
species.
The
increased
incidence
of
vascular
tumors
in
the
male
mice
after
two
years
of
administration
is
of
questionable
biological
significance.
In
the
p53
knockout
mouse
model,
which
was
demonstrated,
to
be
sensitive
to
the
induction
of
vascular
tumors
by
a
genotoxic
reference
compounds,
carbaryl
was
found
to
be
negative.
The
weight
of
the
evidence
indicates
that
carbaryl
shows
no
potential
for
genotoxicity
Epidemiological
data
on
carbaryl
production
workers
show
no
increase
in
tumor
incidence.
As
background,
in
the
two
year
bioassay
conducted
in
the
CD1
mouse,
a
statistically
significantly
higher
incidence
of
vascular
tumors
was
noted
in
males
at
1,000
and
8,000
ppm.
In
females,
no
statistically
significant
change
in
the
incidence
of
vascular
tumors
was
observed.
The
overall
incidence
of
vascular
tumors
was
2,
6,
10
and
10
in
males
and
3,
3,
4
and
9
in
females
at
0,
100,
1,000
and
8,000
ppm
respectively.
In
order
to
address
the
biological
significance
of
the
vascular
tumors,
the
p53
knockout
mouse
model
was
used
as
potential
tool
to
study
chemical
carcinogenesis
(Donehower,
1996).
The
p53
mouse
is
a
genetically
manipulated
mouse
in
which
one
allele
of
the
p53
tumor
suppresser
gene
has
been
inactivated.
One
of
the
assumptions
with
the
knockout
model
is
that
a
mutation
at
the
intact
p53
allele
is
necessary
for
the
development
of
the
carcinogenic
process.
In
principle
non
genotoxic
compounds,
which
induce
tumors
by
other
mechanisms
should
not
induce
tumors
in
this
system.
The
p53
knockout
mouse
model
was
validated
by
testing
two
compounds:
urethane,
a
genotoxic
compound
known
to
produce
vascular
tumors
in
standard
carcinogenicity
bioassays,
and
d
limonene,
17
which
is
neither
genotoxic
nor
carcinogenic
in
mice
but
which
is
known
to
be
carcinogenic
in
the
male
rat
by
a
well
described
non
genotoxic
mechanism.
In
the
validation
study,
the
p53
model
proved
to
be
very
efficient
for
the
induction
of
vascular
tumors
by
genotoxic
compounds
(Bigot,
1999;
Carmichael
et
al.
1999).
Therefore,
this
model
will
produce
an
unambiguous
response
to
specifically
identify
genotoxic
compounds.
Therefore,
carbaryl
was
tested
in
the
p53
mouse.
The
objectives
of
the
studies
were
to
evaluate
if
carbaryl
would
induce
vascular
tumors
in
this
model
and
to
set
a
NOEL
in
this
sensitive
and
specific
model.
Additionally,
this
model
provides
evidence
that
the
tumors
observed
in
the
standard
carcinogenicity
bioassays
resulted
from
an
indirect
geneotoxic
effect
Carbaryl
was
administered
continuously
via
the
diet
to
groups
of
20
male
heterozygous
p53
knockout
mice
at
concentrations
of
0,
10,
30
100,
300,
1,000
and
4,000
ppm
for
at
least
180
days.
At
the
end
of
the
study,
all
animals
were
necropsied,
selected
organs
weighed
and
a
range
of
tissues
were
taken,
fixed
and
examined
microscopically.
Carbaryl
did
not
induce
mortalities
or
clinical
signs
related
to
the
treatment.
Only
a
slight
decrease
in
food
consumption
during
the
first
eight
weeks
was
observed
at
4,000
ppm.
This
observation
was
correlated
with
a
lower
body
weight
evolution
in
comparison
with
the
control
animals.
No
tumors
were
found
in
the
4,000
ppm
group.
In
the
other
treated
groups,
a
few
sporadic
tumors
were
found,
but
they
were
clearly
unrelated
to
treatment
and
representative
of
the
spontaneous
tumor
types
present
in
mice
of
this
age
and
strain.
In
particular,
it
should
be
noted
that
no
tumors
were
found
in
the
liver,
kidney
or
vascular
system,
which
were
seen
in
the
original
mouse
oncogenicity
study
with
carbaryl.
The
only
treatment
related
non
proliferative
change
observed
was
the
presence
of
globular
deposits
in
the
umbrella
cell
layer
of
the
urinary
bladder
at
100
ppm
or
more.
In
conclusion,
the
data
from
the
p53
studies,
the
following
conclusion
can
be
made:
1).
The
p53
model
was
validated
with
urethane
one
of
the
few
compound
known
to
induce
specifically
vascular
tumors.
2).
Carbaryl
was
negative,
and
also
did
not
accelerate
the
formation
of
any
other
tumor
types.
3).
There
is
a
clear
NOEL
at
4000
ppm
in
the
p53
mouse
study
for
carcinogenicity.
4).
Carbaryl
is
not
a
genotoxic
carcinogen.
Thus
the
weight
of
the
evidence
indicates
that
carbaryl
is
not
a
genotoxic
agent
in
humans.
In
addition,
epidemiological
data
on
carbaryl
production
workers
show
no
increase
in
tumor
incidence.
The
two
epidemiology
studies
of
Aventis
CropScience
(formerly
Rhône
Poulenc)
factory
workers
representing
a
sub
18
population
of
the
general
public
with
the
highest
exposure
(i.
e.,
exposure
on
a
daily
basis
over
many
years).
Thus,
the
data
from
these
studies
represent
a
potential
"worst
case"
for
chronic
carbaryl
exposure
to
humans.
The
results
from
these
studies
show
that
the
overall
mortality
experience
of
the
cohort
is
significantly
less
than
expected
when
compared
to
both
United
States
and
West
Virginia
male
death
rates.
In
general,
these
studies
support
conclusion
that
there
were
no
excess
cases
of
cancer
in
this
working
population.
Page:
18
Paragraph:
1
Lines:
1
8
EPA
comment:
Carbaryl
was
not
mutagenic
in
the
Salmonella
typhimurium
assay
or
genotoxic
in
the
Unscheduled
DNA
Synthesis
assay.
In
a
chromosomal
aberration
test
using
Chinese
Hamster
Ovary
(CHO)
cells,
carbaryl
was
clastogenic
in
the
presence
of
S9
activation.
The
CPRC
(1993
meeting)
required
an
in
vivo
cytogenetics
study
in
rodents
to
provide
insight
into
the
structural
and/
or
numerical
aberrations
in
the
study.
The
mouse
micronucleus
study
submitted
to
satisfy
this
requirement
was
deemed
unacceptable.
HED
concluded
that,
based
on
a
Weight
of
the
Evidence
assessment,
the
database
does
not
support
that
carbaryl
acts
as
a
DNA
reactive
mutagen.
However,
this
alone
is
not
sufficient
to
demonstrate
a
mode
of
action
for
establishing
a
threshold
cancer
risk
assessment.
Aventis'
response:
The
Agency
has
previously
granted
a
wavier
for
the
in
vivo
cytogenicity/
micronucleus.
Furthermore,
Aventis
has
fulfilled
the
data
requirement
for
the
in
vivo
mouse
micronucleus
study.
Aventis
believes
that
repeating
the
in
vivo
mouse
micronucleus
study
is
not
appropriate
based
the
fact
that
the
top
dose
in
the
currently
submitted
mouse
micronucleus
was
200
mg/
kg/
day
and
was
similar
to
the
mid
dose
of
250
mg/
kg/
day
tested
in
an
acute
gavage
study
in
mice.
At
the
250
mg/
kg/
day
dose
level
tested
in
the
acute
study
plasma,
RBC,
and
brain
cholinesterase
inhibition
was
seen.
The
percent
cholinesterase
inhibition
observed
was
45.7,
45.7,
and
57.8,
respectively.
At
the
highest
dose
tested
(500
mg/
kg)
in
the
acute
study,
percent
cholinesterase
inhibition
for
plasma,
RBC,
and
brain
were
59.8,
57.1,
and
66.6,
respectively.
Additionally,
the
clinical
signs
observed
at
both
the
250
and
500
mg/
kg
were
very
similar
in
both
findings
and
incidences.
Repeating
the
mouse
micronucleus
study
at
a
slightly
higher
dose
level
would
not
result
in
an
increase
in
significant
clinical
signs.
Therefore,
the
base
results
of
the
study
concerning
clastogenic
or
aneugenic
effects
would
not
change.
Carbaryl
is
not
mutagenic
for
these
endpoints.
Page:
18
Paragraph:
6
Lines:
1
8
EPA
comment:
The
FQPA
Safety
Committee
concluded
at
meetings
on
November
29,
1999
and
April
16,
2001,
that
the
10x
safety
factor
should
be
retained
because:
1)
the
toxicology
data
base
is
incomplete;
there
is
a
data
gap
for
the
multi
generation
reproduction
study
in
rats;
2)
an
assessment
of
susceptibility
following
pre/
post
19
natal
exposure
to
carbaryl
could
not
be
made
due
to
the
data
gap
for
the
reproduction
study;
3)
there
is
concern
for
the
results
of
the
developmental
neurotoxicity
study
(uncertainty
about
NOAEL/
LOAEL
for
brain
morphometric
alterations).
The
Committee
concluded
the
10x
safety
factor
should
be
applied
to
all
population
subgroups
when
assessing
acute
and
chronic
dietary
exposures
and
residential
exposures
of
all
durations.
Aventis'
response:
As
stated
above,
Aventis
has
submitted
to
EPA
a
revised
DNT
Study
and
a
new
2
Generation
Reproduction
Study
which
will
have
a
direct
impact
on
the
FQPA
Safety
Factor.
Aventis
firmly
believes
that
with
the
submission
of
these
two
studies,
the
data
gap
for
the
2
generation
reproduction
study
will
be
fulfilled
and
clarification
of
the
DNT
NOEL
issue
will
be
provided.
Thus
the
Agency
has
the
required
data
to
reduce
the
FQPA
Safety
Factor
from
10X
to
1X.
20
Part
I
Toxicology
Data
Base
SUPPORTING
DISCUSSIONS
Supplemental
Developmental
Neurotoxicity
Study
Findings
The
document
submitted
to
EPA
describes
the
supplemental
histomorphometric
evaluation
performed
on
the
cerebellum
of
rat
pups
and
adults
from
the
carbaryl
developmental
neurotoxicity
study
(Robinson
and
Broxup
2001).
This
additional
work
was
conducted
in
response
to
the
EPA
review
of
the
study
final
report.
In
that
review,
EPA
indicated
that
the
bilateral
decrease
in
the
length
of
the
cerebellum
accompanied
by
a
non
statistically
significant
5%
decrease
in
cerebellar
weights
in
the
day
11
females
and
the
bilateral
increase
in
the
width
of
the
cerebellum
in
the
day
70
female
animals
at
the
highest
tested
dose
(10
mg/
kg/
day)
may
possibly
be
treatment
related.
Further,
some
forebrain
measurements
may
have
also
been
affected.
In
order
to
clarify
the
treatment
relationship
of
these
findings,
the
Agency
recommended
that
additional
morphometric
measurements
be
performed
to
support
the
NOEL
and
that
the
thickness
of
the
cellular
layers
in
the
cerebellum
be
more
fully
described.
The
submitted
report
addresses
the
EPA
comments
by
presenting
additional
evaluations
of
the
high
dose
animals,
only.
The
evaluations
clearly
demonstrate
that
there
are
no
treatment
related
morphometric
findings
in
the
cerebellum
of
male
and
female
pups
and
adults.
These
findings
are
in
agreement
with
the
results
from
the
high
dose
group
animals
in
the
study
final
report
that
found
no
treatment
related
changes
in:
1)
Brain
weights
in
male
and
female
pups;
2)
Cerebellar
weights
in
male
and
female
pups;
3)
Terminal
body
weights
in
male
and
female
pups;
4)
Brain
weights
in
male
and
female
adults;
5)
Terminal
body
weights
in
male
and
female
adults;
6)
FOB
measurements
and
motor
activity
in
male
and
female
pups;
7)
Motor
activity,
auditory
startle
response,
passive
avoidance,
and
water
maze
measurements
in
male
and
female
adults.
The
evaluations
clearly
demonstrate
there
are
no
treatment
related
morphometric
alterations
of
the
cerebellum
in
male
and
female
pups
or
adults
treated
with
carbaryl
at
a
dose
of
10
mg/
kg/
day,
from
Day
6
of
gestation
to
Day
10
post
partum,
inclusively.
In
addition,
in
the
forebrain
no
measurable
bilateral
differences
are
detected
between
control
and
carbaryl
exposed
pups
and
adults.
In
conclusion,
carbaryl
did
not
induce
any
morphologic
or
morphometric
changes
in
either
the
cerebellum
or
the
forebrain
in
animals
receiving
a
high
dose
of
10
mg/
kg/
day.
As
described,
the
new
morphometric
results
revealed
no
changes
at
the
high
dose,
are
in
agreement
with
the
lack
of
treatment
related
effects
on
terminal
body,
brain,
and
cerebellar
weights,
as
well
as
behavioral
and
motor
activity
tests
in
male
and
female
pups
and
adults.
21
2
Generation
Reproduction
Study
Findings
A
2
Generation
reproduction
study
with
carbaryl
technical
was
completed
at
Research
Triangle
Institute
located
in
North
Carolina,
USA,
in
order
to
provide
information
on
the
influence
of
carbaryl
technical
on
the
reproductive
performance
in
rats
(Tyl
et
al.
2001).
The
purpose
of
this
study
was
to
evaluate
the
potential
of
carbaryl,
administered
in
the
feed
to
CD
rats,
to
produce
alterations
in
parental
fertility,
maternal
pregnancy
and
lactation,
and
growth
and
development
of
the
offspring
for
two
generations,
one
litter
per
generation.
This
study
was
performed
in
compliance
with
U.
S.
EPA
FIFRA
GLP
Standards
(U.
S.
EPA,
1989),
the
U.
S.
EPA
OPPTS
Testing
Guidelines
(U.
S.
EPA,
1998),
and
the
OECD
testing
guidelines
for
a
two
generation
reproductive
toxicity
study
(OECD,
1983).
Male
and
female
CD®
(Sprague
Dawley)
rats
(the
FO
generation)
were
administered
carbaryl
(1
naphthyl
methylcarbamate;
CAS
No.
63
25
2)
in
the
feed
at
0,
75,
300,
and
1500
ppm,
available
ad
libitum,
30
animals/
sex/
dose,
for
ten
weeks.
Body
weights
and
feed
consumption
were
recorded
weekly,
and
clinical
signs
were
recorded
at
least
once
daily.
Vaginal
cytology
was
evaluated
for
the
last
three
weeks
of
the
prebreed
period.
Animals
were
then
randomly
mated
within
treatment
groups
for
a
two
week
mating
period
to
produce
the
Fl
generation,
with
exposure
continuing.
FO
males
were
necropsied
after
the
delivery
period,
with
histological
evaluation
of
reproductive
and
other
organs
and
andrological
assessments
(reproductive
organ
weights,
epididymal
sperm
number,
motility
and
morphology,
testicular
homogenization
resistant
spermatid
head
counts,
daily
sperm
production,
and
efficiency
of
daily
sperm
production).
Fl
litters
were
culled
to
ten
pups
on
postnatal
day
(pnd)
4
and
weaned
on
pnd
21.
At
weaning,
up
to
three
weanlings/
sex/
litter
were
necropsied,
and
30/
sex/
dose
were
selected
as
Fl
parents
of
the
F2
generation.
FO
females
were
then
necropsied
with
organ
weights,
stage
of
estrus
at
necropsy,
enumeration
of
ovarian
primordial
follicles,
and
histopathology
of
reproductive
and
other
selected
organs.
Selected
Fl
weanlings,
30/
sex/
dose,
were
administered
carbaryl
in
the
diet
for
a
ten
week
prebreed
exposure
period,
with
acquisition
of
vaginal
patency
in
females
and
preputial
separation
in
males
assessed,
and
vaginal
cytology
for
estrous
cyclicity
in
Fl
selected
females
evaluated
during
the
last
three
weeks
of
the
prebreed
exposure
period.
They
were
mated
for
a
two
week
period,
as
described
above.
At
weaning
of
F2
litters,
up
to
three
weanlings/
sex/
litter
were
necropsied.
Fl
males
were
necropsied
after
the
delivery
period,
with
histopathology
and
andrological
assessments
(as
described
above).
At
weaning
of
the
F2
litters,
parental
Fl
females
were
then
necropsied
with
histopathology,
as
described
above,
and
F2
weanlings,
up
to
three/
sex/
litter,
were
necropsied.
Dietary
exposure
to
carbaryl
for
two
generations,
one
litter
per
generation,
at
0,
75,
300,
and
1500
ppm,
resulted
in:
decreased
body
weights
and
decreased
weight
gains
in
P0
and
P1
parental
males
and
females,
accompanied
by
decreased
feed
consumption
at
1500
ppm,
and
slightly
reduced
body
weights
and
feed
consumption
at
300
ppm;
Fl
and
P2
offspring
toxicity
(reduced
body
weights
during
lactation
beginning
on
post
natal
day
(pnd)
4
through
lactation
and
continuing
in
selected
P1
offspring
through
acquisition
of
puberty)
at
1500
ppm;
increases
in
P1
pup
mortality
at
1500
ppm
and
in
P2
pup
mortality
22
at
300
ppm
and
1500
ppm
during
lactation,
especially
early
(pnd
0
4),
accompanied
by
reduced
maternal
body
weights
in
FO
and
P1
dams
at
1500
ppm
and
300
ppm,
and
delayed
vaginal
opening
and
preputial
separation
in
selected
Fl
offspring
at
1500
ppm
considered
an
indirect
effect
related
to
body
weight
decreases.
In
conclusion,
the
NOELs
for
carbaryl
administered
in
the
diet,
in
CD®
(SD)
rats
under
the
conditions
of
this
study,
were:
°
parental
systemic
toxicity:
75
ppm
°
parental
reproductive
toxicity:
1500
ppm
°
offspring
toxicity:
75
ppm
EPIDEMIOLOGIC
DATA
Epidemiological
data
on
carbaryl:
standardized
mortality
ratio
analysis
of
employees
exposed
to
carbaryl
at
the
Rhône
Poulenc
Institute,
West
Virginia
plant.
The
National
Institute
of
Occupational
Safety
and
Health
(NIOSH)
and
the
Union
Carbide
Corporation
(UCC)
on
chemical
production
plants
in
the
Kanawha
Valley
(KV)
of
West
Virginia
originally
initiated
an
epidemiological
study.
One
of
the
plants
included
in
this
extensive
epidemiology
study
was
the
facility
at
which
carbaryl
is
produced
in
Institute,
West
Virginia.
The
plant
was
acquired
by
Rhône
Poulenc
(now
Aventis
CropScience)
from
UCC
in
December
1986.
The
study
(Pastides
1993)
reported
here
investigated
the
total
and
cause
specific
mortality
experience
of
employees
exposed
to
carbaryl
at
the
production
plant.
No
additional
information
other
than
what
was
available
in
the
original
database
was
collected
about
the
health
or
mortality
experience
of
individuals
employed
at
this
plant
for
this
study.
The
central
results
of
this
report
were
presented
in
terms
of
Standardized
Mortality
Ratios
(SMR's)
and
95%
confidence
intervals
(95%
CI's).
Carbaryl
technical
is
manufactured,
packaged,
and
shipped
from
the
Aventis
CropScience
plant
in
Institute,
West
Virginia.
Besides
carbaryl,
the
plant
also
produces
other
agricultural
products.
In
the
past,
numerous
other
chemical
compounds
were
produced
there,
including
butanol,
styrene,
acetaldehyde,
toluene,
fluorocarbons
and
others.
Carbaryl
is
produced
in
crystalline
form,
as
well
as
in
an
oil
based
solution
(41%
carbaryl).
Final
processing
includes
crystallizing,
drying,
bin
storage,
and
packing.
Exposure
to
carbaryl
would
occur
among
three
basic
categories
of
employees:
those
in
the
manufacturing
unit,
those
in
maintenance,
and
those
in
packaging
and
distribution.
For
employees
of
the
carbaryl
unit,
UCC
tracked
through
1988
the
vital
status,
and
cause
of
death
information,
of
all
individuals
who
were
first
hired
between
the
start
up
of
the
carbaryl
unit
in
1960
through
1978.
Employees
hired
after
1978
were
not
part
of
the
NIOSH/
UCC
KV
study.
23
Using
the
KV
database,
UCC
conducted
SMR
analyses
of
the
employees
from
the
entire
Institute
plant
in
the
past.
However,
no
separate
examination
of
data
from
employees
specifically
exposed
to
carbaryl
was
made.
In
the
overall
Institute
study,
no
excess
risk
in
total
mortality,
total
cancer
mortality,
or
site
specific
cancer
mortality,
was
observed.
In
the
carbaryl
specific
study,
a
total
of
522
employees
were
identified
within
the
UCC
database
as
belonging
to
one
of
the
three
carbaryl
exposure
groups;
(158
Carbaryl
Production,
229
Packing
and
Distribution,
327
Maintenance)
Because
of
some
overlap
between
the
groups
and
because
some
individuals
did
not
meet
the
NIOSH/
UCC
cohort
entry
criteria,
the
final
number
of
employees
available
for
the
SMR
analysis
was
488.
These
488
employees
contributed
7,531.5
person
years
to
the
mortality
analysis.
This
number
represents
the
combined
number
of
years
in
which
these
employees
were
followed
through
1988.
As
of
the
end
of
1988,
twenty
five
deaths
were
identified
from
this
cohort
of
employees.
Elevated
SMR's,
reflecting
an
observed
number
of
deaths
greater
than
the
number
expected
were
seen
for
cancer
of
the
pancreas,
cancer
unspecified,
and
cancer
of
the
brain
and
other
parts
of
the
nervous
system.
In
the
former
two
categories,
the
excess
was
slight
and
based
on
only
a
single
death;
furthermore
the
wide
confidence
intervals
suggest
a
relatively
imprecise
SMR
estimate
and
one
that
is
well
within
the
range
of
chance
variation.
In
the
case
of
brain
and
nervous
system
cancer,
the
higher
SMR
suggested
a
possibility
of
some
association
with
work
in
the
carbaryl
unit,
yet
the
very
wide
confidence
interval
indicates
that
the
SMR
estimate
has
low
precision.
In
other
words,
the
estimate
is
unstable,
is
within
the
range
of
chance
variation,
and
reflects
the
small
sample
size
on
which
it
is
based.
Furthermore,
review
of
the
death
certificates
of
these
two
individuals
revealed
that
these
tumors
were
of
different
histologic
origin;
one
was
reported
as
an
astrocytoma,
the
other
as
a
glioblastoma
multiforme.
This
information
reduces
the
plausibility
that
both
malignancies
were
caused
by
the
same
exposure.
The
next
phase
of
the
carbaryl
plant
worker
epidemiology
study
has
been
completed
(Pastides
and
Zorn,
1997),
and
the
results
are
based
on
vital
status
of
employees
through
1994.
The
new
cohort
consisted
of
817
employees
(488
from
the
previous
analysis
and
329
who
were
hired
after
1978).
Taking
into
account
restriction
criteria,
as
described
in
the
report,
the
restricted
cohort
that
reflects
the
number
of
employees
who
worked
across
departments
is
599.
As
previously
shown,
the
overall
mortality
experience
of
the
cohort
is
significantly
less
than
expected
when
compared
to
both
United
States
and
West
Virginia
male
death
rates.
In
general,
the
follow
up
study
supported
the
results
from
the
initial
study
that
there
were
no
excess
cases
of
cancer
in
this
working
population.
24
Carcinogenicity
Issue
–
Historical
Perspective
and
as
presented
to
JMPR
and
submitted
to
EPA
in
2000
A.
Combined
Oncogenicity/
Chronic
Toxicity
Studies
1)
Carbaryl
produced
tumors
primarily
at
the
highest
dose
tested.
The
dietary
concentrations
in
the
rat
study
were
0,
250,
1500,
and
7500
ppm
(approximately
13,
75,
and
375
mg/
kg
b.
w.);
for
the
mouse
study
the
concentrations
of
technical
carbaryl
were
0,
100,
1000,
and
8000
ppm
(approximately
12,
143,
and
1143
mg/
kg).
The
highest
doses
were
chosen
to
satisfy
the
U.
S.
EPA
requirement
for
an
MTD,
while
the
lower
doses
were
selected
for
determining
the
NOEL
and
to
produce
moderate
toxicity
in
tissues
and
on
cholinesterase.
Considering
an
approximate
acute
oral
LD
50
in
rats
and
mice
of
250
mg/
kg,
these
doses
would
therefore
be
equivalent
to
0.06,
0.6
and
4.6
times
the
acute
oral
LD
50
for
mice
and
0.05,
0.3
and
1.5
times
the
acute
oral
LD
50
for
rats.
(The
high
doses
for
the
mouse
and
rat,
respectively,
also
would
be
equivalent
on
a
body
weight
basis
to
a
70
kg
person
consuming
approximately
80
grams
and
26
grams
of
technical
carbaryl
per
day
for
a
lifetime.)
These
MTD
levels
caused
a
significant
reduction
in
body
weight
and
body
weight
gain
in
both
species,
especially
early
in
the
study.
Several
other
parameters,
such
as
cholinesterase,
were
also
significantly
affected
throughout
the
studies
at
the
top
doses.
The
U.
S.
EPA
in
their
review
of
the
studies
agreed
that
the
highest
doses
in
the
mouse
and
rat
study
exceeded
the
MTD.
As
a
result,
these
MTD
levels
were
deemed
inappropriate
for
chronic
testing.
Therefore,
the
only
relevant
findings
for
establishing
a
carcinogenic
classification
are
the
vascular
system
tumors
in
male
mice.
2)
The
data
supporting
the
oncogenic
potential
of
carbaryl
is
equivocal
since
tumors
occurred
only
at
one
site
of
one
sex
of
one
species
when
irrelevant
data
at
doses
exceeding
the
MTD
are
excluded
from
consideration.
Rat
Study
In
the
rat
carcinogenicity
study,
carbaryl
produced
tumors
in
both
sexes
(thyroid
and
bladder
in
males;
liver
and
bladder
in
females)
but
only
at
the
MTD
(375
mg/
kg).
At
the
low
and
intermediate
doses
(13
and
75
mg/
kg,
respectively)
there
was
no
indication
of
an
increased
incidence
of
tumors
at
any
of
the
sites
for
which
increases
occurred
at
the
top
dose.
Thus,
at
levels
less
than
the
MTD,
carbaryl
has
not
produced
tumors
in
rats,
whether
considering
the
current
study
or
a
previous
study
in
which
another
rat
strain
was
tested.
25
Mouse
Study
In
the
mouse
carcinogenicity
study,
carbaryl
produced
tumors
(liver
and
vascular)
in
females
only
at
the
highest
dose
tested
(1143
mg/
kg).
At
the
low
and
intermediate
doses
(12
and
143
mg/
kg,
respectively)
there
was
no
indication
of
an
increased
incidence
of
tumors
at
any
of
the
sites
for
which
increases
occurred
at
the
top
dose.
Thus,
at
doses
less
than
the
MTD,
carbaryl
did
not
produce
tumors
in
female
mice
in
the
current
study
or
in
an
older
study.
In
male
mice,
carbaryl
produced
tumors
in
the
vascular
system
and
kidney
at
the
highest
dose
tested
(1143
mg/
kg
b.
w.).
At
the
low
and
intermediate
doses
(12
and
143
mg/
kg)
there
was
no
indication
of
an
increased
incidence
in
kidney
tumors.
At
the
low
and
intermediate
doses
there
was
an
apparent
increase
in
the
incidence
of
vascular
tumors
as
follows:
Dose
Male
Mouse
Vascular
Tumors
(mg/
kg)
Benign
Malignant
Total
0
122
12
1
6
7
143
1
9
10
1143
3
7
10
However,
despite
a
nearly
10
fold
increase
in
dose
increments,
the
total
tumors
observed
at
the
intermediate
and
high
doses
were
the
same.
The
number
of
malignant
tumors
actually
was
slightly
lower
at
the
high
dose
than
at
the
intermediate
dose.
Thus,
these
results
show
there
is
no
clear
linear
dose
response
relationship
from
the
intermediate
dose
to
the
high
dose,
despite
a
nearly
10
fold
difference
in
dose
increment.
With
regard
to
statistical
significance,
the
performing
laboratory
indicated
that
statistical
significance
was
just
achieved
at
the
p<
0.05
levels
for
the
top
dose,
while
the
intermediate
dose
results
were
just
above
this
level
of
statistical
significance
(this
result
was
due
to
the
actuarial
type
statistical
analysis
used
for
tumor
incidence
and
onset).
However,
the
U.
S.
EPA
and
U.
K.
authorities
have
performed
separate
statistical
analyses
and
the
tumor
incidence
at
the
intermediate
dose
also
was
found
to
fall
within
statistical
significance.
Based
on
the
results
from
the
original
study
report,
a
NOEL
could
be
established
based
on
the
lowest
dose
tested
at
approximately
12
mg/
kg
b.
w.
However,
arguments
are
made
in
succeeding
sections
that
18
month
historical
control
data
from
the
performing
laboratory
are
inadequate
to
determine
if
the
incidence
of
tumors
at
any
of
these
doses
is
biologically
significant.
As
previously
stated,
vascular
tumors
were
produced
in
the
female
mice
but
only
at
the
top
dose
and
with
a
very
similar
incidence
(N
=
9)
as
observed
in
the
males
at
the
top
dose.
In
most
other
aspects
of
the
study,
e.
g.,
body
weight
effects,
clinical
signs,
clinical
26
pathology,
etc.,
the
females
reacted
very
similar
to
males.
However,
there
was
no
indication
of
an
increased
incidence
of
vascular
tumors
in
females
at
the
low
or
intermediate
doses
as
was
observed
in
the
male
mice.
Thus,
these
facts
raise
questions
regarding
the
biological
significance
of
the
vascular
tumors,
which
occurred
in
the
male
mice.
3)
Adequate
historical
control
data
were
not
available
from
the
laboratory
conducting
the
chronic
toxicity
and
oncogenicity
studies.
Historical
data
from
the
laboratory
at
which
the
mouse
oncogenicity
study
was
conducted
was
only
available
for
studies
conducted
up
to
18
months.
Aventis
CropScience
was
not
certain
if
these
data
accurately
reflected
the
incidence
of
vascular
tumors
in
24
month
CD
1
mice.
Additional
information
was
obtained
from
other
sources
and
summarized
(Klonne,
1995)
to
compare
historical
control
data
from
several
sources
and
at
several
study
intervals
to
that
of
the
data
for
the
carbaryl
study.
The
following
key
observations
were
made:
An
increase
in
the
spontaneous
vascular
tumor
incidence
appears
to
occur
from
18
to
24
months
of
age
in
mice.
An
increase
in
the
spontaneous
vascular
tumor
incidence
over
the
last
10
years
may
be
occurring
in
CD
1
mice.
The
carbaryl
study
(a
2
year
study)
should
be
compared
to
historical
control
data
from
2
year
old
mice
generated
during
the
last
10
years.
In
general,
considering
the
most
relevant
historical
control
data
outside
of
the
performing
laboratory,
the
incidences
of
vascular
tumors
in
major
organs
(spleen/
liver)
in
male
mice
at
the
low
and
middle
doses
fall
within
the
historical
control
ranges.
4)
The
lack
of
significant
histopathological
findings
at
the
one
year
interim
sacrifice
of
both
the
mouse
and
rat
studies
did
not
correlate
with
the
detection
of
tumors
in
certain
tissues
at
the
end
of
the
study.
To
further
investigate
the
mechanism
by
which
carbaryl
induced
multiple
tumors
in
the
rat
and
the
mouse
after
two
years
of
exposure,
a
decision
was
made
to
re
evaluate
the
histological
slides
of
target
organs
from
the
interim
sacrifice
after
one
year
of
treatment.
The
purpose
of
this
work
was
to
identify
if
subtle
changes
present
at
one
year
could
explain
the
appearance
of
tumors
seen
at
two
years.
Histopathological
examinations
were
conducted
on
the
target
organs
(liver,
kidney,
thyroid
gland,
urinary
bladder)
from
the
control
and
high
dose
groups
in
rats
and/
or
mice.
The
review
was
conducted
independently
by
two
of
Aventis
CropScience's
pathologists
(Debruyne
and
Irisarri,
1996).
In
the
rat,
at
the
end
of
a
52
week
exposure
period
to
carbaryl
technical
by
the
dietary
27
route,
the
re
evaluation
of
the
histological
slides
revealed
the
presence
of
microscopic
changes
not
previously
reported
in
the
bladder
(transitional
epithelial
hyperplasia
in
both
male
and
females),
kidney
(pelvic
urothelial
hyperplasia
in
males),
and
thyroid
(thyroid
follicular
hypertrophy
in
males)
and
liver
(hepatocellular
hypertrophy
in
males
and
females).
In
the
mouse,
no
microscopic
changes
were
detected
at
the
end
of
the
52
week
exposure
period.
These
new
findings
prompted
the
Aventis
CropScience
to
conduct
further
studies
to
confirm
cell
proliferation
in
the
various
tissues
(associated
with
positive
tumor
formation)
and
to
re
examine
the
histological
slides
from
the
chronic
toxicity
and
oncogenicity
studies.
5)
Oncogenicity
and
chronic
toxicity
slide
review
Aventis
CropScience
then
commissioned
independent
pathologists
to
re
examine
the
histological
slides
at
the
1
year
and
2
year
sacrifices
from
the
chronic
toxicity
and
oncogenicity
studies
to
determine
what
other
(if
any)
discrepancies
exist
outside
of
those
determined
by
the
Aventis
CropScience's
internal
review.
This
peer
review
study
was
conducted
according
to
US.
EPA
Peer
Review
policy
guidelines.
The
results
of
this
review
showed
no
differences
from
the
original
study
pathologists
review.
B.
Carcinogenic
Mechanism
1)
Subsequent
to
the
two
year
studies,
Aventis
CropScience
proactively
performed
in
vivo
genotoxicity
studies.
In
response
to
the
results
of
the
mouse
oncogenicity
study,
Aventis
CropScience
proactively
conducted
an
in
vivo
DNA
adduct
study
in
mice
at
a
concentration
similar
to
the
top
dose
used
in
the
two
year
carcinogenicity
study
(i.
e.,
8000
ppm)
to
determine
if
carbaryl
caused
any
genotoxic
effects
(Sagelsdorff,
P.
1994).
Results
indicated
that
carbaryl
did
not
interact
with
the
DNA
in
mice,
even
at
the
excessive
dose
used
in
the
study.
Additionally,
an
in
vivo
rat
bone
marrow
chromosomal
aberration
study
was
conducted
and
showed
that
carbaryl
did
not
produce
chromosomal
aberrations
at
doses
up
to
approximately
50%
of
the
acute
oral
LD
50
(McEnaney,
1993).
Although
there
was
no
indication
of
genotoxic
effects
in
the
rat
chromosomal
aberration
and
mouse
DNA
adduct
studies,
Aventis
CropScience
recently
conducted
an
in
vivo
micronucleus
study
in
mice
to
determine
if
carbaryl
produced
aneuploidy
in
this
species.
Results
from
the
mouse
micronucleus
assay
again
showed
no
genotoxic
effects
(Marshall,
1996).
Thus,
results
from
these
in
vivo
studies
indicate
that
the
mechanism
of
action
of
carbaryl
in
the
production
of
tumors
in
the
two
year
oncogenicity
studies
does
not
occur
via
a
direct
genotoxic
effect.
28
2)
The
weight
of
the
evidence
approach
indicates
that
carbaryl
shows
little
potential
as
a
genotoxin.
There
have
been
nearly
50
literature
and
Aventis
CropScience
reports
on
the
genotoxicity
of
carbaryl.
The
number
of
test
systems
and
endpoints
is
extensive.
In
neither
bacterial
nor
mammalian
cell
cultures
has
carbaryl
demonstrated
any
significant
mutagenic
potential.
In
various
in
vitro
DNA
damage
and
repair
assays
there
is
no
convincing
evidence
to
suggest
that
carbaryl
produces
DNA
damage.
While
carbaryl
has
shown
some
clastogenic
potential
in
vitro,
these
changes
occur
at
or
near
cytotoxic
levels.
In
addition,
studies
performed
in
vivo,
the
mouse
DNA
adduct
and
rat
chromosomal
aberration
(previously
discussed),
a
mouse
dominant
lethal
study,
and
an
evaluation
for
mouse
micronucleated
polychromatic
erythrocytes
all
have
been
negative.
The
absence
of
tumor
induction
in
a
6
month
carcinogenicity
study
conducted
in
the
p53
knockout
mouse
demonstrated
that
the
tumors
observed
in
the
standard
two
year
bioassays
in
rats
and
mice
are
not
linked
to
an
indirect
genotoxic
mechanism.
3)
It
is
possible
that
altered
metabolism
from
unrealistically
high
doses
of
carbaryl
plays
a
significant
role
in
the
formation
of
these
tumors.
The
results
from
the
metabolism
study
indicated
that
the
carbaryl
was
almost
completely
absorbed
and
metabolized
(approximately
90%)
and
that
there
was
essentially
no
difference
in
the
metabolism
between
the
sexes
or
in
the
low
versus
the
high
dose.
Likewise,
there
was
no
difference
in
the
metabolism
between
the
single
versus
multiple
doses.
The
data
also
indicated
that
the
low
dose
was
almost
completely
eliminated
in
12
hours
and
the
high
dose
was
almost
completely
eliminated
in
24
hours.
Two
metabolites,
5,6
dihydro
5,
6
dihydroxy
carbaryl
and
3,4
dihydro
3,
4
dihydroxy
carbaryl
were
identified
to
be
approximately
8%
and
1%,
respectively,
of
the
total
dose
and
were
found
to
be
primarily
conjugated
to
glucuronide.
These
metabolites
are
very
likely
result
from
the
metabolism
of
epoxide
intermediates.
Other
metabolites,
which
were
likely
formed
from
the
epoxide
intermediates,
were
identified
as
5
hydroxycarbaryl
(13%)
and
4
hydroxycarbaryl
(6%)
and
conjugated
carbaryl
(3%).
Epoxide
intermediates
have
been
proposed
to
be
the
proximate
carcinogen
for
several
classes
of
carcinogens.
Depending
on
such
factors
as
the
stability
of
the
epoxide
intermediate,
the
ability
of
the
cell
to
detoxify
the
epoxide
(related
to
such
factors
as
the
available
glutathione
stores,
epoxide
hydrase
activity,
etc.),
the
excretion
pattern
of
the
compound,
etc.,
these
reactive
intermediates
may
be
routinely
handled
by
the
body
just
like
other
endogenous
epoxides
or
could
be
available
to
react
with
cellular
components.
Thus,
it
is
possible
that
excessively
high
doses
of
carbaryl
could
alter
the
normal
metabolism,
distribution,
and/
or
excretion
pattern
in
many
different
ways,
e.
g.,
saturate
the
normal
metabolic
pathways
with
a
shift
of
carbaryl
metabolism
through
the
epoxide
29
intermediates,
deplete
the
available
glutathione
stores
available
for
conjugation,
increase
the
half
life
of
the
epoxide
intermediates,
increase
tissue
concentrations
of
carbaryl
and
its
metabolites
due
to
diminished
ability
for
excretion,
etc.
Additionally,
saturation
of
many
enzyme
systems
with
large
carbaryl
substrate
concentrations
could
allow
accumulation
of
endogenous
chemicals
and
by
products
of
normal
metabolism
that
would
otherwise
be
detoxified
and
excreted.
4)
Vascular
tumors.
In
the
two
year
bioassay
conducted
in
the
CD1
mouse,
a
statistically
significantly
higher
incidence
of
vascular
tumors
was
noted
in
males
at
1,000
and
8,000
ppm.
In
females,
no
statistically
significant
change
in
the
incidence
of
vascular
tumors
was
observed.
A
search
of
the
literature
indicated
there
is
very
few
chemical
agents
known
to
induce
vascular
tumors
in
humans,
among
them
utherane
and
vinyl
chloride
were
identified
(Creech,
J.
L.
Jr
et
Johnson,
M.
N.
1974).
Angiosarcoma
of
liver
in
the
manufacture
of
polyvinyl
chloride.
(J.
Occup.
Med.
16:
150
151;
Marion,
M.
J.,
De
Vivo,
I.,
Smith,
S.,
Luo,
J.
C.
and
Brandt
Rauf,
P.
W.
1996).
The
molecular
epidemiology
of
occupational
carcinogenesis
in
vinyl
chloride
exposed
workers
(Int.
Arch.
Occup.
Environ.
Health,
68:
394
398)
and
the
mechanism
underlying
the
formation
of
vascular
tumors
is
through
the
formation
of
etheno
adducts,
formed
maybe
by
reactive
oxygen
species
(Barbin,
A.
2000.
Etheno
adduct
forming
chemicals:
from
mutagenicity
testing
to
tumor
mutation
spectra.
Mutation
Res.
462:
55
69:
Nair,
J.,
Barbin,
A.,
Velic,
I.
and
Bartsch,
H.
1998).
Etheno
DNA
base
adducts
from
endogenous
reactive
species
(Mutation
Res.
424:
59
69).
All
those
compounds
would
have
been
found
to
induce
vascular
tumors
in
the
p53
model.
Thus,
the
study
using
the
genetically
modified
heterozygous
p53
knockout
mouse
was
designed
to
address
the
potential
role
of
an
indirect
genotoxic
mechanism
in
the
induction
of
vascular
tumors
in
mice.
Carbaryl
was
administered
continuously
via
the
diet
to
groups
of
20
male
heterozygous
p53
knockout
mice
at
concentrations
of
0,
10,
30
100,
300,
1,000
and
4,000
ppm
for
at
least
180
days.
No
treatment
related
tumors
were
found
even
in
the
highest
dose
ppm
group.
In
particular,
it
should
be
noted
that
no
tumors
were
found
in
the
liver,
kidney
or
vascular
system.
Under
the
conditions
of
this
study,
the
NOEL
is
4,000
ppm
(approximately
716
mg/
kg
b.
w./
day)
for
neoplastic
changes.
C.
Epidemiological/
Worker
Exposure
Information
Epidemiological
evaluations
of
carbaryl
production
workers,
the
population
of
exposed
persons
with
the
highest
and
most
consistent
carbaryl
exposure,
show
no
indication
of
effects
on
tumor
incidence.
The
two
epidemiology
studies
of
Aventis
CropScience
factory
workers
representing
a
sub
population
of
the
general
public
with
the
highest
exposure
(i.
e.,
exposure
on
a
daily
basis
over
many
years).
Thus,
the
data
from
these
studies
represent
a
potential
worstcase
for
chronic
carbaryl
exposure
to
humans.
The
results
from
these
studies
show
that
30
the
overall
mortality
experience
of
the
cohort
is
significantly
less
than
expected
when
compared
to
both
United
States
and
West
Virginia
male
death
rates.
In
general,
these
studies
support
conclusion
that
there
were
no
excess
cases
of
cancer
in
this
working
population.
SUMMARY
Aventis
CropScience
strongly
believes
that
the
use
of
carbaryl
products
present
no
imminent
carcinogenic
risk
to
users
based
on
the
following
points:
Current
data
support
a
hypothesis
that
high
doses
of
carbaryl
in
life
time
studies
produce
tumors
via
a
non
genotoxic
mechanism,
possibly
related
to
altered
metabolism
at
these
high
doses
At
doses
less
than
the
MTD,
there
was
an
increased
incidence
of
tumors
only
in
1
site
of
1
sex
of
1
species.
The
increased
incidence
of
vascular
tumors
in
the
male
mice
after
two
years
of
administration
is
of
questionable
biological
significance
In
the
p53
knockout
mouse
model,
which
was
demonstrated,
to
be
sensitive
to
the
induction
of
vascular
tumors
by
a
genotoxic
reference
compound,
carbaryl
was
found
to
be
negative
The
weight
of
the
evidence
indicates
that
carbaryl
shows
little
potential
for
genotoxicity
Epidemiological
data
on
carbaryl
production
workers
show
no
increase
in
tumor
incidence
31
REFERENCES
1.
Bigot,
D.
1999.
Validation
on
Transgenic
Mice
–
p53
Knockout
Mice
–
to
Predict
Rodent
Carcinogenicity.
Non
Guideline
Study.
Rhône
Poulenc
Agro.
Study
No.
SA
97040.
November
10,
1999.
460pp.
MRID
45281802.
2.
Carmichael
NGC,
Debruyne
ELM
and
Bigot
Lasserre
D.
2000
The
p53
heterozygous
knockout
mouse
as
a
model
for
chemical
carcinogenesis
in
vascular
tissue.
Envi.
Health
Perspective.
108:
61
65.
3.
Debruyne,
E.
and
Irisarrri,
E.
(1996).
Carbaryl
technical
chronic
toxicity
study
in
the
rat
(HWA
Study
No.
656
139)
and
the
mouse
(HWA
Study
No.
656
138):
evaluation
of
histological
slides.
Rhône
Poulenc
agrochimie
report
No.
R&
D/
CRSA/
TOX
HPA
4.
Unpublished
report.
MRID
45365503.
4.
Donehower
LA:
The
p53
deficient
mouse:
a
model
for
basic
and
applied
cancer
studies.
Semin.
Cancer
Biol.,
7,
269
278
(1996).
5.
Klonne,
D.
R.
1995.
Carbaryl
mouse
historical
control
data
position
paper,
November
1995.
Rhône
Poulenc.
74
pp.
MRID
45365501.
6.
Marshall,
R.
1996.
Carbaryl:
induction
of
micronuclei
in
the
bone
marrow
of
treated
mice.
CH
Study
No.
198/
89
1052.
Corning
Hazelton.
Unpublished
report.
MRID
44069301.
7.
McEnaney,
S.
1993.
Study
to
evaluate
the
chromosome
damaging
potential
of
carbaryl
technical
by
its
effects
on
the
bone
marrow
cells
of
treated
rats.
Hazelton
Microtest.
Hazleton
U.
K.
Study
No.
198/
64.
Unpublished
report.
MRID
43039301.
8.
Pastides,
H.
1993.
Standardized
mortality
ratio
analysis
of
employees
exposed
to
carbaryl
at
the
Rhône
Poulenc
Institute,
West
Virginia
Plant.
Unpublished
report.
MRID
42901501.
9.
Pastides,
H.,
and
M.
Zorn.
1997.
An
evaluation
of
the
mortality
experience
of
carbaryl
unit
employees
at
the
Rhône
Poulenc
Institute,
West
Virginia
Plant.
Unpublished
report.
MRID
44349901
10.
Sagelsdorff,
P.
1994.
Investigation
of
the
potential
of
protein
and
DNA
binding
of
carbaryl.
CIBA
GEIGY
Limited
Toxicology
Services/
Cell
biology.
Study
No.
CB93/
52,
unpublished
report.
MRID
43282201.
11.
Robinson,
K.
and
Broxup,
B.
2001
A
Developmental
Neurotoxicity
Study
of
Orally
Administered
Carbaryl,
Technical
Grade,
in
the
Rat.
Lab.
I.
D.
Number
97391.
Performed
by
ClinTrials
BioResearch
Ltd.
34
pages.
Submitted
to
EPA
in
July
2001.
12.
Tyl,
R.
W.,
Myers,
C.
B.,
and
Marr,
M.
C.
2001
Two
Generation
Reproductive
Toxicity
Evaluation
of
Carbaryl
(RPA007744)
Administered
in
the
Feed
to
CD
(Sprague
Dawley)
Rats.
RTI
I.
D.
Number
65C
07407
400.
Performed
by
Research
Triangle
Institute.
906
pages.
Submitted
to
EPA
in
June
2001.
32
Part
II
Dietary
and
Water
Exposure/
Risk
Assessment
Line
by
Line
Review
of
the
Dietary
and
Water
Exposure
Assessment
of
the
Human
Health
Risk
Assessment
Document
for
Carbaryl
(June
19,
2001)
1.0
Executive
Summary
Page:
3
Paragraph:
5
Line:
3
EPA
Comment:
No
acceptable
two
year
reproduction
study
is
available.
Aventis
Response:
A
study
has
been
completed
and
submitted.
The
data
gap
to
remove
the
10X
FQPA
safety
factor
has
been
filled.
Page:
6
Paragraph:
2
Line:
1
EPA
Comment:
Monitoring
data
for
carbaryl
residues
in
ground
and
surface
water
are
available
but
they
are
of
limited
utility
in
developing
estimated
environmental
concentrations
for
the
aggregate
dietary
(food
and
water)
risk
assessment.
Aventis
Response:
Monitoring
data
submitted
by
Aventis
is
directly
applicable
to
drinking
water
residue
use
in
the
aggregate
(food
and
water)
assessment.
Worst
case
community
water
supply
systems,
targeted
for
maximum
carbaryl
use,
were
monitored
for
three
years
on
a
weekly
basis
during
peak
carbaryl
use
times.
4.0
Exposure
Assessment
and
Characterization
4.2.1
Residue
Profile
Page:
25
Paragraph:
2
Line:
1
EPA
Comment:
HED
conducts
dietary
risk
assessments
using
the
DEEM™
which
incorporated
consumption
data
generated
in
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(CSFII),
1989
1992.
Aventis
Response:
The
CSFII
data
for
the
years
1994
1996
have
been
available
for
several
years
now.
These
data
should
be
used
as
it
reflects
the
most
recent
eating
patterns
and
habits
of
the
U.
S.
population
that
is
currently
available.
33
Page:
26
Paragraph:
3
Lines:
1
5
EPA
Comment:
Most
of
the
processing
factors
were
obtained
from
processing
studies
submitted
by
the
registrant
and
compiled
in
a
memo
entitled
"Carbaryl
Anticipated
Residues
for
Carcinogenic
Dietary
Risk
Assessment."
S.
Hummel,
12/
3/
93.
Aventis
Response:
The
studies
in
this
memo
are
older
processing
studies
submitted
in
the
1980's
or
even
earlier.
New
residue
processing
studies
were
done
in
the
early
to
midnineties
in
conjunction
with
the
Residue
Chemistry
DCI.
These
studies
are
listed
with
MRID
numbers
in
EPA's
Product
and
Residue
Chemistry
documents.
The
factors
are
listed
in
the
`Discussion
Section'
below.
These
factors
should
be
used
in
the
dietary
risk
assessment
as
they
represent
newer,
GLP
data.
Page:
27
Paragraph:
1
Line:
5
EPA
Comment:
As
discussed
in
section
3.2,
the
10X
safety
factor
is
retained
for
carbaryl.
Aventis
Response:
The
data
gaps
and
concerns
for
the
FQPA
safety
factor
have
been
addressed
by
Aventis
with
the
submission
of
the
2
generation
rat
reproduction
study
and
the
additional
data
generated
for
the
developmental
neurotoxicity
study.
Based
upon
the
outcome
of
the
studies
provided,
the
10X
safety
factor
is
no
longer
justified
and
should
be
removed.
There
are
no
populations
of
concern
in
this
assessment
when
the
corrected
RfD
is
used
in
the
risk
calculation
(excluding
poultry
and
using
the
CMBS
data).
4.2.2
Acute
Dietary
Exposure
Assessment
Page:
29
Table
6:
EPA
Comment:
The
top
heading
of
the
table
is
labeled
"Acute
All
Commodities
at
the
99.9
th
percentile
of
exposure
(Market
Basket
Survey
Data
Used
in
Place
of
PDP/
FDA
data.)
Aventis
Response:
This
top
table
heading
should
be
labeled:
"Acute
All
Commodities
at
the
99.9
th
Percentile
of
Exposure
(Market
Basket
Survey
Data
Not
Included).
4.2.5
Characterization/
Uncertainties
of
the
Risk
Estimates
34
Page:
31
Paragraph:
1
Line:
1
EPA
Comment:
Cooking
factors
were
available
for
potatoes
only.
Aventis
Response:
A
survey
of
the
literature
data
revealed
numerous
cooking
and
washing
studies
for
carbaryl.
See
`Discussion
Section'
for
a
list
of
these
studies
and
a
table
of
processing/
washing/
cooking
factors
that
can
be
derived
for
carbaryl
from
these
literature
studies.
4.3
Water
Exposure/
Risk
Pathway
Page:
31
Paragraph:
5
Line:
4
EPA
comment:
Some
non
targeted
monitoring
data
are
available
but
they
are
of
limited
utility
in
developing
estimated
environmental
concentrations
(EECs)
for
ecological
and
human
health
risk
assessment.
Aventis'
response:
Aventis
believes
that
the
highest
estimated
EECs
of
relevance
for
ecological
risk
assessment
are
not
relevant
for
estimating
human
health
risks
due
to
the
lack
of
proximity
of
drinking
water
sources
to
likely
areas
of
highest
ecological
risk.
The
drinking
water
monitoring
program
conducted
by
the
registrant
provides
a
real
world
assessment
of
the
potential
for
human
exposure
to
carbaryl
in
drinking
water
derived
from
surface
water.
Drinking
water
concentrations
derived
from
PRZM/
EXAMS
greatly
overestimate
the
potential
exposure
to
carbaryl
in
drinking
water,
generally
by
several
orders
of
magnitude.
Monitoring
Data
Page:
32
Paragraph:
4
Line:
2
(and
elsewhere)
EPA
comment:
USGS
NAQWA
(sic)
program
Aventis'
response:
The
correct
abbreviation
for
the
USGS
water
monitoring
program
is
NAWQA.
Page:
32
Paragraph:
5
Line:
2
EPA
comment:
Because
of
limitation
in
the
analytical
methods
used
there
is
some
question
as
to
the
accuracy
of
carbaryl
analysis.
35
Aventis'
response:
This
generalized
statement
needs
to
be
qualified
or
deleted.
Whereas
the
authors
of
reports
written
as
part
of
the
NAWQA
program
have
been
clear
about
the
potential
limitations
of
the
quantitative
nature
of
the
carbaryl
data
in
the
database,
they
have
also
been
clear
about
the
validity
of
the
qualitative
nature
of
the
data.
The
use
of
the
multi
residue
method
in
the
NAWQA
program
does
have
some
limitations
as
a
result
of
the
large
numbers
of
diverse
pesticides
and
degradation
products
that
they
are
monitoring.
However,
the
QC/
QA
data
generated
as
part
of
the
NAWQA
program
(described
in
the
discussion
section
on
surface
water
at
the
end
of
the
EFED
response)
demonstrates
the
validity
of
the
detections
of
carbaryl
in
the
studies.
The
monitoring
study
conducted
by
the
registrant,
and
reported
in
this
section,
does
not
have
the
same
potential
limitations
in
the
analytical
method
since
the
method
is
looking
specifically
for
only
carbaryl.
Therefore,
the
analytical
method
used
by
the
registrant
does
not
raise
questions
about
the
accuracy
of
the
carbaryl
analysis.
Page:
32
Paragraph:
5
Line:
3
EPA
comment:
Poor
analytical
methods
probably
have
resulted
in
lower
detection
rates
and
lower
concentrations
than
actually
present.
Aventis'
response:
This
generalized
statement
should
be
deleted
for
reasons
provided
above
and
in
the
discussion
section
of
the
EFED
response.
Page:
33
Paragraph:
2
Line:
6
EPA
comment:
The
data
do
not
give
a
good
indication
of
the
effectiveness
of
treatment
because
samples
existing
and
entering
the
treatment
plant
were
different.
In
several
cases,
finished
water
had
higher
concentrations
than
raw
water
and
finished
water
had
detectable
carbaryl
when
the
raw
did
not.
Aventis'
response:
Obtaining
matched
samples
is
not
possible
because
of
varying
residence
time
through
the
treatment
system,
as
well
as
mixing
that
occurs.
The
minimal
amount
of
carbaryl
residues
found
also
made
observations
regarding
treatment
less
definitive.
However,
an
examination
of
the
data
does
indicate
that
carbaryl
concentrations
were
generally
lower
in
finished
water
than
in
raw
water
samples
collected
at
the
same
time.
These
data
do
include
several
instances
where
carbaryl
was
detected
over
a
few
weeks
in
the
raw
water
so
the
effect
of
sample
time
is
less
important.
The
statement
regarding
several
cases
of
finished
water
having
higher
concentrations
than
raw
water
is
misleading
and
certainly
does
not
consider
the
analytical
uncertainty
for
concentrations
below
the
level
of
quantification
and
near
the
level
of
detection.
There
were
only
two
cases
when
finished
water
was
greater
than
raw
water
when
the
concentrations
in
finished
water
were
greater
than
0.01
ppb
(only
one
third
of
the
quantification
limit).
One
36
case
was
when
the
raw
water
was
0.009
ppb
and
the
finished
water
was
0.011
ppb.
These
two
analyses
are
essentially
equivalent,
especially
considering
that
they
are
only
about
a
third
of
the
quantification
limit.
The
other
case
was
at
the
Deerfield
community
water
system.
This
drinking
water
facility
uses
a
small
river
without
a
reservoir
as
a
source
for
a
small
Community
Water
System.
Farms
are
located
immediately
upstream
of
the
facility.
The
intake
is
also
not
continuous
(shut
down
over
weekends).
Therefore,
getting
a
matching
sample
is
quite
difficult,
especially
for
a
short
duration
spike
as
a
result
of
spray
drift,
summer
thunderstorm,
or
perhaps
a
spill
that
almost
immediately
enters
the
river
as
a
runoff
event.
The
rarity
of
this
event
is
demonstrated
by
the
absence
of
residues
of
this
magnitude
the
next
year
(2000).
Samples
collected
through
this
time
of
the
year
in
2001
also
do
not
indicate
a
similar
event.
Although
the
data
from
this
site
cannot
be
used
to
determine
the
peak
concentration,
the
data
provide
a
distribution
of
residues
through
the
three
year
period
which
will
define
up
to
the
99
th
percentile
concentration
of
the
distribution.
The
Deerfield,
Michigan
community
water
system
is
one
of
the
systems
in
which
the
greatest
variability
of
residues
would
be
expected.
Most
of
the
other
community
water
systems
are
located
on
larger
rivers,
lakes,
or
reservoirs.
Because
the
design
of
study
called
for
analysis
of
finished
water
only
when
there
were
residues
in
the
raw
water,
there
was
only
one
finished
sample
analyzed
when
the
raw
water
contained
no
residues.
This
sample
was
collected
at
the
Deerfield
community
water
system
at
the
sampling
interval
after
the
finding
of
0.16
ppb
in
the
Deerfield
system.
The
residue
level
in
this
sample
was
0.004
ppb.
The
difference
between
0.004
ppb
and
non
detect
is
insignificant,
and
if
real
can
probably
be
attributed
to
water
at
much
higher
concentrations
remaining
in
the
system
from
the
previous
week.
Page:
33
Paragraph:
2
Line:
10
EPA
comment:
This
illustrates
that
carbaryl
contamination
is
transient,
and
that
it
is
unlikely
that
any
sampling
would
catch
the
actual
peak
concentration
Aventis'
response:
The
role
of
a
peak
concentration
is
in
dietary
exposure
assessment
is
undergoing
re
examination
within
EPA.
The
current
policy
of
EPA
appears
to
define
a
certain
percentile
as
an
appropriate
value
for
use
in
screening
assessments,
but
the
exact
percentile
to
be
used
is
being
defined
by
EPA
management.
For
more
comprehensive
assessments,
a
distribution
of
values
is
preferred.
The
peak
concentration
in
this
study
was
measured
at
a
community
water
system
on
a
small
river.
The
registrant
agrees
that
the
sampling
schedule
was
not
adequate
to
determine
the
true
peak
in
such
systems.
Most
of
the
other
community
water
systems
are
located
on
larger
rivers,
lakes,
or
reservoirs.
Therefore,
the
peak
values
are
not
likely
to
be
an
order
of
magnitude
greater
than
37
the
amounts
detected
in
this
monitoring
program.
Page:
33
Paragraph:
2
Line:
13
EPA
comment:
Non
targeted
monitoring,
such
as
the
NAWQA
program
has
shown
that
much
higher
concentrations
occur.
Aventis'
response:
The
main
reason
why
the
drinking
water
monitoring
study
did
not
show
residues
as
high
as
in
the
NAWQA
program
is
the
location
of
the
sampling
points.
Drinking
water
supplies
tend
to
be
located
on
larger
surface
water
bodies
than
NAWQA
sampling
points
(or
in
other
words,
the
intakes
for
community
water
systems
tend
to
be
downstream
of
NAWQA
sampling
points).
This
additional
time
allows
for
additional
degradation
and
dilution
to
occur.
Finding
the
highest
concentration
at
the
Deerfield,
Michigan
system
is
not
surprising
since
this
intake
is
on
one
of
the
smallest
surface
water
bodies
included
in
the
monitoring
study.
Page:
33
Paragraph:
2
Line:
14
EPA
comment:
This
study,
while
useful,
does
not
provide
sufficient
information
to
allow
estimation
of
actual
peak
and
mean
concentrations
that
actually
occur
in
all
areas
or
the
effect
of
treatment.
Aventis'
response:
Because
most
of
the
samples
did
not
contain
carbaryl
residues,
accurate
estimates
of
the
actual
peak
and
mean
concentrations
can
not
be
obtained.
However,
the
distributions
obtained
from
all
sites
can
be
used
to
define
up
to
the
99
th
percentile
concentration.
The
average
cannot
be
accurately
determined;
however,
the
timeweighted
average
is
only
slightly
above
the
limit
of
detection
(and
certainly
less
than
0.01
ppb)
at
all
20
sites.
The
study
provides
information
on
concentrations
of
carbaryl
in
community
water
systems
most
likely
to
contain
the
highest
concentrations
of
carbaryl.
Residues
of
carbaryl
in
other
areas
would
be
expected
to
be
lower.
The
study
does
not
provide
information
on
concentrations
in
smaller
surface
water
bodies
or
in
areas
where
surface
water
is
not
used
for
drinking
water.
Because
drinking
water
concentrations
are
what
is
needed
for
FQPA
dietary
calculations,
this
information
is
suitable
for
use
in
dietary
exposure
assessments.
Page:
34
Table
8
EPA
comment:
Carbaryl
EEC
Values
Aventis'
response:
Aventis
has
provided
a
more
detailed
response
to
this
same
table
that
is
presented
as
Table
6
in
the
draft
EFED
chapter.
An
electronic
copy
of
the
EPA
Memorandum
on
"Refined
Estimated
Environmental
Concentrations
for
38
Carbaryl"
(DP
Bar
Code
D267276,
authored
by
E.
Laurence
Libelo,
July
23,
2001,
and
sent
to
Anthony
E.
Britten
and
Virginia
Dobozy)
was
provided
to
Aventis
and
contains
the
PRZM
model
inputs
that
were
used
to
generate
the
EECs
shown
in
this
table.
An
abbreviated
version
of
our
response
to
the
information
from
EFED
is
included
below.
It
would
be
useful
to
add
another
column
to
Table
8
to
specify
which
method
of
application
was
used
to
generate
the
EECs.
It
would
also
be
of
benefit
for
the
Agency
to
state
which
of
the
carbaryl
labels
were
used
to
develop
the
"maximum"
label
application
rate
scenarios.
The
model
parameters
listed
in
the
Memorandum
show
that
the
"average"
scenarios
for
citrus
and
apples
were
conducted
using
aerial
applications.
Few
applications
to
these
crops
are
made
aerially.
Therefore,
the
model
results
overestimate
the
contributions
from
spray
drift
since
the
"average"
applications
to
these
crops
are
made
using
ground
airblast
equipment
with
lower
spray
drift
inputs.
The
"maximum
label
rate"
application
scenario
for
apples
that
is
allowed
by
the
Sevin
brand
XLR
PLUS
label
(E.
P.
A.
Reg.
No
264
333),
the
Sevin
brand
80WSP
and
CHIPCO
Sevin
brand
80WSP
labels
(E.
P.
A.
Reg.
No
264
526)
and
the
CHIPCO
Sevin
brand
SL
label
(E.
P.
A.
Reg.
No
264
335)
is
5
applications
at
3
lb.
ai/
A/
application
made
every
14
days.
The
scenario
used
in
the
model
applies
less
than
the
maximum
amount
of
product
allowed
by
the
labels.
In
addition,
application
timing
was
used
in
the
modeling
for
the
Index
Reservoir
scenario
(applications
made
by
air
every
4
days)
that
would
be
a
violation
of
the
Aventis
labels
that
restrict
applications
to
a
minimum
of
every
14
days.
The
"average"
scenario
for
sweet
corn
in
Ohio
should
be
3
applications
at
1.1
lb
ai/
A/
application
(as
noted
in
the
memo,
"Average
application
rate
from
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD")
and
not
the
2
applications
at
3.4
lb
ai/
A/
application
as
listed
in
the
table.
The
PRZM
input
file
shows
the
correct
inputs
of
3
applications
at
1.1
lb
ai/
A/
application.
Likewise,
the
"average"
scenario
for
sugar
beets
in
Minnesota
should
be
1
application
at
1.3
lb
ai/
A/
application.
The
"Citrus"
scenario
would
be
more
appropriately
labeled
Oranges.
For
the
average
scenario,
the
3.4
lb.
ai/
A/
application
rate
listed
in
Table
8
is
for
oranges
which
is
the
highest
"average"
application
rate
for
any
type
of
citrus.
Therefore,
this
"average"
scenario
for
oranges
is
at
the
high
end
for
all
citrus
and
overestimates
the
EECs
for
use
in
the
other
citrus
crops.
4.3.1
DWLOCs
for
Acute
Dietary
Exposure.
39
Page:
35
Paragraph:
1
Line:
7
EPA
Comment:
Therefore,
there
is
no
allowable
contribution
for
water
to
the
risk
cup.
Aventis
Response:
Based
on
a
corrected
acute
reference
dose
for
carbaryl
(no
10X
FQPA
safety
factor)
and
the
exposure
assessment
that
uses
the
Carbamate
Market
Basket
Data,
DWLOCs
can
be
calculated.
(see
`Discussion
Section'
for
calculations.)
4.3.2
DWLOCs
for
Chronic
Dietary
Exposure
Page
36
Table
9
EPA
Comment:
DWLOC(
chronic)
calculations
in
Table.
Aventis
Response:
Based
on
a
corrected
chronic
reference
dose
for
carbaryl
(no
10X
FQPA
safety
factor)
the
DWLOCs
should
be
calculated
as
shown
in
the
`Discussion
Section'.
Based
on
the
corrected
values,
there
are
no
population
subgroups
of
concern.
8.0
Data
Needs/
Label
Requirements
Product
Chemistry
Data
Gaps
Page:
97
Paragraph:
2
Line
1
EPA
Comment:
Additional
data
are
required
depicting
carbaryl
residue
in/
on
cotton
gin
byproducts.
Aventis
Response:
Aventis
is
not
supporting
the
cotton
use
and
has
removed
this
crop
from
the
labels.
Aventis
CropScience
requested
cancellation
of
this
use
in
a
letter
to
Mr.
George
Tompkins,
RD,
on
January
22,
1999.
A
Federal
Register
Notice
dated
April
14,
1999
announced
receipt
by
the
Agency
of
an
application
from
RhonePoulenc
Ag
Company
(now
Aventis
CropScience)
to
cancel
the
use
of
carbaryl
products
on
cotton
40
Line
by
Line
Review
of
the
Supporting
Document
"Revised
Dietary
Exposure
Analysis
for
the
HED
Revised
Human
Health
Risk
Assessment
(Felicia
A.
Fort;
April
26,
2001)"
Conclusions/
Summary
Page:
2
Paragraph:
1
Line:
8
EPA
comment:
At
the
present
time,
information
from
the
industry
sponsored
Carbamate
Market
Basket
Survey
has
not
been
completely
approved
for
use
in
dietary
risk
assessments.
Aventis
Response:
The
CMBS
protocols
were
presented
to
EPA
for
comment
before
the
studies
were
started.
These
studies
were
specifically
conducted
to
obtain
more
realistic
residues
for
consumer's
"at
the
plate"
to
be
used
in
dietary
assessments.
As
agreed
with
EPA
before
this
study
was
started,
the
CMBS
data
should
take
precedence
over
others
for
use
in
dietary
assessment
(after
their
quality
review
has
been
completed).
Chronic
Page:
2
Paragraph:
2
Line:
8
EPA
comment:
When
poultry
is
not
considered
in
the
risk
estimate,
the
dietary
exposure
is
<
6%
of
the
cPAD
for
all
population
subgroups.
Aventis
Response:
When
a
corrected
cRfD
is
used
(no
FQPA
10X)
and
poultry
is
not
included
in
the
risk
estimate,
the
dietary
exposure
is
<
0.6%
of
the
cRfD
for
all
population
subgroups.
Acute
Page:
3
Continuation
from
Paragraph:
4
of
Page
2
Line:
3
EPA
Comment:
Subsequent
dietary
analyses
and
all
additional
sensitivity
analyses
were
conducted
without
poultry;
the
risk
estimates
were
still
of
concern
for
all
population
subgroups
with
the
all
infants
population
subgroup
consuming
260%
of
the
aPAD
when
CMBS
data
were
used.
Aventis
Response:
When
a
corrected
aRfD
is
used
(no
FQPA
10X)
,
there
are
no
concerns
for
all
population
subgroups.
The
all
infants
population
subgroup
consumes
26%
of
the
aRfD
when
CMBS
data
are
used.
41
Residue
Data
Page:
5;
Paragraph:
2;
Line:
4
EPA
comment:
FDA
monitoring
data
were
used
for
…
cherries,
raspberry,
blueberry,
raspberry,
asparagus,
…
Aventis
response:
Second
listing
of
"raspberry"
can
be
deleted.
Page:
5;
Paragraph:
2;
Line:
9
EPA
comment:
Field
trial
data
were
used
for
the
commodities,
garden
beets,
turnips,
mustards,
dried
beans,
almonds,
pecans,
walnuts,
field
corn
grain,
rice,
flax
seed,
okra,
olive,
peanuts,
pistachio,
and
sunflower.
Aventis
response:
According
to
Table
6a,
the
following
commodities
should
be
added
to
this
list:
sugar
beets
and
dried
peas
Page:
5;
Paragraph:
2;
Line:
11
EPA
comment:
For
oysters,
the
tolerance
of
2
ppm
was
used
in
the
assessment.
Aventis
response:
According
to
Table
6a,
the
tolerance
of
0.2
ppm
was
also
used
for
Dill
(fresh)
in
the
assessment.
Processing
Factors
Page
6
Paragraph:
1
Table
2
EPA
comment:
Most
of
the
carbaryl
processing
factors
were
obtained
from
processing
studies
submitted
by
the
registrant
and
compiled
in
a
memo
entitled
"Carbaryl
Anticipated
Residues
for
Carcinogenic
Dietary
Risk
Assessment",
S.
Hummel,
12/
3/
93.
Aventis
Response:
As
previously
state,
the
studies
in
this
memo
were
older
processing
studies
submitted
in
the
1980's
or
even
earlier.
New
residue
processing
studies
were
done
in
the
early
to
mid
nineties
in
conjunction
with
the
Residue
Chemistry
DCI.
These
studies
are
listed
with
MRID
numbers
in
EPA's
Product
and
Residue
Chemistry
documents.
The
factors
are
listed
in
the
Discussion
section.
These
factors
should
be
used
in
the
dietary
risk
assessment
as
they
represent
newer,
GLP
data.
42
Consumption
data
Page:
7
Paragraph:
1
Line:
1
EPA
Comment:
HED
conducts
dietary
risk
assessments
using
the
DEEM™
which
incorporated
consumption
data
generated
in
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(CSFII),
1989
1992.
Aventis
response:
As
previously
stated
the
CSFII
data
for
the
years
1994
1996
have
been
available
for
several
years
now.
These
data
should
be
used
as
it
reflects
the
most
recent
eating
patterns
and
habits
of
the
U.
S.
population
that
is
currently
available.
Results
Page:
7
Paragraph:
2
Line
2
EPA
comment:
Additional
cooking
and
processing
studies
would
allow
further
refinement.
Aventis
response:
A
literature
search
resulted
in
many
literature
references
to
cooking,
washing
and
peeling
studies
for
carbaryl
treated
commodities.
Average
cooking,
washing
factors
can
be
derived
from
these
literature
studies.
See
the
`Discussion
Section'
for
a
list
of
the
references
and
the
average
calculated
factors.
Characterization/
Uncertainties
of
the
Risk
Estimates.
Page:
9
Paragraph:
2
Line:
1
EPA
comment:
Additional
cooking
factors
could
further
reduce
the
risk
estimates.
Aventis
response:
Numerous
literature
studies
have
been
conducted
on
other
commodities,
see
the
`Discussion
Section'.
Attachment
1:
Anticipated
Residues
Summary
and
Residue
Distribution
Files
Table
6a:
Summary
of
Anticipated
Residues
for
Carbaryl
(Market
Basket
Data
not
included)
and
Table
6b:
Summary
of
Market
Basket
Survey
Data.
Aventis
Comments:
EPA/
BEAD
reports
a
maximum
of
84%
crop
treated
for
cranberries
and
an
average
of
39%
crop
treated
for
cranberries.
Three
years
of
data
were
obtained
from
the
Cranberry
Institute
(memo
from
Gary
Deziel,
Manager
of
Research
and
Communication,
Cranberry
Institute.)
These
data
show
maximum
acres
treated
43
for
1992,
39%;
1996,
37%;
and
1998,
36%.
Based
on
these
data
and
private
conversations,
the
maximum
percent
crop
treated
for
cranberries
is
39%
with
an
average
of
37%.
Barley,
oats,
rye
and
cotton/
cottonseed
are
not
supported
by
Aventis
and
should
not
be
included
in
the
risk
assessment.
A
letter
date
May
7,
1999
to
Ms.
Kathryn
Boyle
confirmed
Rhône
Poulenc's
(now
Aventis
CropScience)
decision
not
to
support
the
registration
of
carbaryl
products
on
the
commodities
barley,
oats,
and
rye.
These
uses
have
been
deleted
from
our
technical
and
end
use
product
labels.
Residue
Data
Sources:
The
following
data
sources
are
more
appropriate
to
use
for
the
crops
listed
in
the
table,
according
to
priority
rules
for
use
of
residue
data
(Market
Basket
(MBS)>
PDP>
FDA>
Field
Trial
(FT)>
tolerance)
and
the
Translation
of
Monitoring
Data
HED
SOP
99.3
(March
26,
1999).
Food
EPA
Used
More
Appropriate
Source
Brussels
Sprouts
Cabbage
FDA
Lettuce
MBS
Cabbage
Cabbage
FDA
Lettuce
MBS
Collards
Mustard
FT
Spinach
PDP
Eggplant
Pepper
FDA
Tomato
MBS
Endive
Leaf
lettuce
FDA
Spinach
PDP
Kale
Mustard
FT
Spinach
PDP
Kohlrabi
Cabbage
FDA
Broccoli
MBS
Mustard
Greens
Mustard
FT
Spinach
PDP
Paprika
H.
Pepper
FDA
Tomato
MBS
Chili
Pepper
H.
Pepper
FDA
Tomato
MBS
Other
Pepper
H.
Pepper
FDA
Tomato
MBS
Sweet
Pepper
S.
Pepper
FDA
Tomato
MBS
Pimentos
H.
Pepper
FDA
Tomato
MBS
Strawberries
Strawberry
FDA
Strawberry
PDP
Strawb.
Juice
Strawberry
FDA
Strawberry
PDP
Swiss
Chard
Celery
PDP
Spinach
PDP
Page
41
Residue
Distribution
Files
RDF#
68
Almonds
and
RDF#
69
Chestnuts
appear
to
have
used
the
almond
hull
field
trial
data
rather
than
the
almond
nutmeat
field
trial
(mostly
NDs)
data
for
the
residue
values.
Page
44
Residue
Distribution
Files
RDF#
86
to
RDF#
92.
Meat
and
milk.
There
is
no
clear
indication
or
discussion
anywhere
in
the
document
regarding
the
source
of
these
residue
data
or
how
the
values
were
derived
(e.
g.,
derived
from
theoretical
animal
diets
or
monitoring
data).
(see
Discussion
below).
44
Part
II
Dietary
and
Water
Exposure/
Risk
Assessment
SUPPORTING
DISCUSSIONS
Surface
Water
Concentrations
In
section
5.0,
page
33
(Table
6),
EPA
has
based
its
assumptions
about
concentrations
of
carbaryl
in
drinking
water
upon
model
simulations.
The
data
from
the
registrant
drinking
water
monitoring
program
provide
the
best
estimate
of
concentrations
of
carbaryl
in
drinking
water.
This
study
uses
the
sampling
design
for
acute
endpoints
recommended
in
industry/
EPA
meetings
during
1999
(weekly
sampling
during
times
of
peak
concentrations
over
a
three
year
period).
Twenty
sites
representing
the
highest
carbaryl
use
areas
were
selected
based
on
the
information
provided
in
Appendix
I.
Included
are
16
sites
in
agricultural
areas
and
4
locations
in
urban
areas.
Samples
were
collected
from
the
inlet
and
outlet
water
at
each
sampling
interval.
Outlet
samples
were
only
analyzed
when
residues
were
present
in
the
inlet
samples.
The
analytical
method
had
a
limit
of
quantification
of
0.030
ppb
and
a
limit
of
detection
of
0.002
ppb.
Error!
Reference
source
not
found.
summarizes
the
results
of
the
monitoring
at
each
of
the
20
community
water
systems.
The
maximum
concentration
observed
was
0.16
ppb
(average
of
four
samples,
the
highest
was
0.18
ppb)
in
a
finished
water
sample
from
the
Deerfield
community
water
system
located
on
the
River
Raisin
in
Lenawee
County,
Michigan.
There
were
only
five
other
samples
above
the
limit
of
quantification
of
0.030
ppb.
One
was
a
raw
water
sample
containing
0.31
ppb
from
the
Little
Potato
Slough
Mutual
community
water
system
near
Lodi
in
San
Joaquin
County,
California
(the
source
is
the
Little
Potato
Slough).
The
corresponding
finished
water
sample
was
0.007
ppb.
A
second
one
was
a
raw
water
sample
in
Brockton,
MA
which
contained
0.031
ppb.
No
detectable
residues
were
found
in
the
corresponding
finish
water
sample.
The
last
three
samples
were
from
the
Shades
Mountain
plant
of
the
Birmingham
community
water
system
on
the
Cahaba
River
in
Jefferson
County,
Alabama
.
Two
were
raw
and
finished
samples
of
0.038
and
0.032
ppb
at
the
same
sampling
interval
in
2001.
The
other
sample
was
0.035
ppb
in
the
raw
water
in
a
2000
sample
(the
corresponding
finished
sample
did
not
contain
carbaryl
residues.
All
residues
were
transient
so
the
time
weighted
average
concentration
of
carbaryl
in
each
of
the
years
was
0.005
ppb
or
less
at
all
20
community
water
systems.
45
Table
1.Summary
of
results
from
the
carbaryl
drinking
water
monitoring
study.
Site
Major
Uses
Maximum
Concentration
(ppt)
TWA
Conc.
(ppt)*
in
Outlet
Water
Inlet
Water
Outlet
Water
1999
2000
2001**
1999
2000
2001**
1999
2000
Manatee,
FL
citrus
9
3
ND
11
ND
NA
1
1
West
Sacramento,
CA
orchards,
nuts
3
24
ND
3
10
NA
1
1
Lodi,
CA
orchards,
nuts
12
31
ND
4
7
NA
1
1
Riverside,
CA
grapes,
tree
crops
8ND
ND
ND
NANA
1
1
Lake
Elsinore,
CA
citrus
ND
3
6
NA
NA
Analysis
Pending
1
1
Corona,
CA
citrus
ND
ND
ND
NA
NA
NA
1
1
Beaumont,
TX
various
agricultural
ND
ND
ND
NA
NA
NA
1
1
Point
Comfort,
TX
rice,
tree
crops
18
5ND
ND
NDNA
1
1
Penn
Yan,
NY
grapes,
apples
ND
23
ND
NA
ND
NA
1
1
Westfield,
NY
grapes,
apples
21
5
ND
ND
9
NA
1
1
Jefferson,
OR
vegetables,
strawberries
ND
10
ND
NA
ND
NA
1
1
Coweta,
OK
pecans
4
ND
***
ND
NA
***
1
1
Pasco,
WA
apples,
potatoes
2
3
ND
ND
ND
NA
1
1
Manson,
WA
apples
ND
ND
ND
NA
NA
NA
1
1
Deerfield,
MI
vegetables
10
4
ND
160
ND
NA
5
1
Brockton,
MA
cranberries
31
27
ND
ND
3
NA
1
1
East
Point,
GA
home
and
garden
18
18
4
3
8
ND
1
1
Midlothian,
TX
home
and
garden
14
ND
14
ND
NA
ND
1
1
Cary,
NC
home
and
garden
4ND
ND
ND
NANA
1
1
Birmingham,
AL
home
and
garden
23
35
38
ND
ND
32
1
1
*
Annual
Time
Weighted
Concentration,
outlet
values
substituted
for
inlet
values
when
available;
values
below
the
detection
limit
were
considered
to
be
half
the
detection
limit.
**
Results
represent
one
to
six
months
of
sampling
into
the
third
year
program.
***
No
results
available
for
the
third
year
of
sampling.
46
ND
Not
detected.
NA
No
outlet
samples
analyzed
due
to
carbaryl
residues
not
being
detected
in
inlet
samples.
Appropriateness
of
the
Carbamate
Market
Basket
Survey
Data
The
Agency
questions
the
appropriateness
of
the
use
of
these
data
in
several
discussions
of
the
dietary
risk
assessment.
The
CMBS
Task
Force
met
with
EPA/
HED
before
the
start
of
the
study
to
review
the
purpose
of
the
study
and
protocols
for
the
study.
The
EPA
assured
the
task
force
that
the
study
data
would
be
used
in
risk
assessments,
taking
precedence
over
all
other
monitoring
or
field
trial
data
available
for
those
crops.
A
surrogation
plan
according
to
HED
SOP
99.3
was
also
assured.
The
specific
target
of
this
study
was
to
measure
more
realistic
residues
that
consumer's
are
exposed
to
"at
the
plate".
The
study
protocol
was
designed
to
mimic
the
typical
consumer
shopping
at
his/
her
local
grocery
store
and
the
preparation
he
would
do
at
home
before
consuming
or
further
cooking/
preparing
the
food.
The
PDP
data
is
taken
from
distribution
centers
before
the
grocery
stores
are
reached
and
some
typical
preparation
is
done.
The
CMBS
data
would
therefore
be
expected
to
have
somewhat
lower
and
more
realistic
measures
of
residues
consumers
are
exposed
to.
There
is
likely
to
be
even
further
reduction
of
residues
before
the
food
is
"put
on
the
plate"
by
storing,
cooking,
slicing,
peeling
or
other
preparation.
It
would
be
very
difficult
to
justify
within
the
industry,
further
generation
of
these
much
needed
data
for
other
crops/
compounds
if
EPA
decided
at
this
late
date
that
the
data
could
not
be
used.
Secondary
Residues
Although
residue
distribution
files
are
presented
by
the
Agency
in
Attachment
1
of
the
Dietary
Assessment
Support
Document
for
meat
and
milk
commodities,
there
is
no
place
in
the
document
where
these
residue
numbers
and
residue
distribution
files
are
discussed.
Aventis
neither
can
determine
the
source
of
the
residue
data
was
(monitoring
or
theoretical
animal
diets)
nor
how
the
data
were
translated
or
calculated.
We
request
that
a
more
detailed
description
of
this
process
be
provided
to
us.
Processing
Factors
EPA
uses
processing
factors
listed
in
a
1993
memo
by
S.
Hummel.
Examination
of
this
document
shows
that
the
source
of
these
processing
factors
is
studies
that
were
conducted
in
the
1980s
or
even
earlier.
As
part
of
the
Residue
Chemistry
DCI
for
carbaryl
in
the
early
1990s,
numerous
residue
processing
studies
were
conducted
along
with
residue
(RAC)
field
trials.
These
studies
are
referenced
in
the
Product
and
Residue
Chemistry
Support
Document
prepared
by
the
EPA.
These
processing
studies
and
the
derived
factors,
which
were
conducted
under
GLP
conditions
to
more
recent
specifications,
are
the
factors
that
should
be
used
in
the
current
dietary
risk
assessment.
A
table
of
these
factors
is
listed
here.
47
Food
Process
Average
PF
Citrus
Dried
Pulp
1.46
Juice
0.
06
Oil
13.92
Molasses
0.47
Field
Corn
Small
grits
0.25
Meal
0.25
Flour
0.25
Starch
0.25
Crude
Oil
3.
38
Refined
Oil
0.
25
Grapes
Pasteurized
Juice
0.
24
Wet
Pomace
1.37
Dry
Pomace
3.85
Processed
Raisins
1.
37
Unprocessed
Raisins
2.
17
Raisin
Waste
4.
88
Olives
Olive
oil
0.
81
Peanuts
Meal
0.29
Refined
Oil
0.
29
Pome
Juice
0.
40
Wet
Pomace
1.26
Dry
Pomace
3.70
Potatoes
Wet
Peel
1.00
Dry
Peel
0.75
Flakes
0.75
Chips
0.
75
Rice
Polished
Rice
0.03
Hulls
2.37
Bran
0.36
Soybeans
Hulls
0.35
Meal
0.22
Crude
Oil
2.
71
Refined
Oil
0.
005
Sunflowers
Hulls
0.35
Meal
0.03
Crude
Oil
0.
18
Refined
Oil
0.
03
Tomatoes
Juice
0.
52
Wet
Pomace
1.74
Dry
Pomace
2.89
Puree
1.
26
Paste
2.
01
Wheat
Middlings
0.42
Shorts
0.83
Asp
Grain
Fractions
11.79
LG
Flour
0.08
Patent
Flour
0.10
Wheat
Germ
0.65
Wheat
Bran
1.03
48
Cooking
Washing
Factors
EPA
states
several
times
that
cooking/
washing
studies
would
further
reduce
the
anticipated
residues
used
in
the
assessment
and
reduce
the
risk
estimates.
Aventis
conducted
a
general
literature
search
for
studies
such
as
this.
A
table
of
factors
is
listed
followed
by
the
references
found
in
the
general
literature.
Average
cooking,
washing
and
canning
factors
could
be
derived
from
these
references
and
applied
to
the
risk
assessment
as
supported
by
these
literature
studies.
Food
Process
Reduction
Reference
Broccoli
Cooking/
washing
55%
8
Cabbage
Heads
Cooking
90%
2
Cabbage
Heads
Washing
75%
2
Cauliflower
Cooking/
washing
94%
4
Grapes
Washing
49%;
85%
7
Green
Beans
Canning
100%
11
Green
Beans
Cooking/
blanching
81%
11
Green
Beans
Washing
52%
11
Okra
Cooking
42%;
25%
1,14
Okra
Cooking/
steaming
82%
1,14
Okra
Washing
80%;
66%;
70%
1,14
Onions
Washing
89%;
98%;
100%
9
Orchard
Fruit
Washing
50%
12
Peas
Cooking/
boiling
85%
3
Peas
Washing
70%
3
Spinach
Canning
99.5%
10
Spinach
Washing
70%
10
Tomatoes
Peeling/
washing
99%
5,6
Tomatoes
Puree/
catsup
98%
5,6
Tomatoes
Washing
66%;
68%,
84%
5,6
1.
Indian
Journal
of
Plant
Protection.
1996,
24,
86
89.
2.
Pest
Management
and
Econ.
Zoology.
1994,
2,
131
134.
3.
Plant
Protection
Bulletin.
1988,
40,
12
13.
4.
Beitrage
zur
Trop.
Land.
Veter.
1982,
20,
89
95.
5.
Indian
Journal
of
Entomology.
1978,
40,
187
190.
6.
Indian
Journal
of
Entomology.
1973,
34,
31
34.
7.
Indian
Journal
of
Ag
Sciences.
1978,
48,
179
183.
8.
J.
Ag.
Food
Chem.
1969,
15,
215
216.
9.
J.
Food
Science
Technology.
1978,
15,
215
216.
10.
J.
Ag.
Food
Chem.
1968,
16,
967
973.
11.
J.
Ag.
Food
Chem.
1968,
16,
962
966.
12.
J.
Assoc.
Off.
Anal.
Che,.
1989,
72,
533
535.
13.
Env.
Health
Criteria
1994,
153,
358pp.
49
14.
Indian
Journal
of
Ag
Sciences.
1976,
45,
139
144.
15.
Indian
Journal
of
Env.
Health
Acute
DWLOC
EPA
indicates
there
is
no
room
in
the
risk
cup
for
water
and
DWLOCs
cannot
be
calculated.
If
a
corrected
acute
RfD
is
used
(no
FQPA
10X),
acute
DWLOCs
can
be
calculated
as
follows:
US
Population:
Acute
RfD=
0.03
mg/
kg
Exposure=
0.005937
mg/
kg
(from
EPA
assessment
without
poultry
and
with
CMBS
data)
70
kg.
Man,
2
liter
consumption
Acute
DWLOC
is
842ppb
Children
1
6:
Acute
RfD=
0.03
mg/
kg
Exposure=
0.008363
mg/
kg
(from
EPA
assessment
without
poultry
and
with
CMBS
data)
10kg
child,
1
liter
consumption
Acute
DWLOC
is
216ppb
Aventis
monitoring
programs
of
raw
surface
drinking
water
have
shown
0.16
ppb
as
the
maximum
encountered.
NAWQA
data
shows
5
ppb
as
the
maximum
encountered
in
ground
or
surface
water.
These
monitoring
numbers
would
indicate
there
is
no
concern
for
dietary
and
drinking
water
exposure
in
an
aggregate
situation.
Chronic
DWLOCs
EPA
indicates
there
is
some
concern
for
subpopulations
for
drinking
water
in
the
chronic
scenarios.
If
a
corrected
chronic
RfD
is
used
(no
FQPA
10X)
chronic
DWLOCs
can
be
calculated
as
follows:
US
Population:
Chronic
RfD=
0.01
mg/
kg
Exposure
=
0.000037
mg/
kg
(from
EPA
assessment
without
poultry)
70kg
man,
2
liter
consumption
Chronic
DWLOC
is
349
ppb
Children
1
6:
Chronic
RfD=
0.01
mg/
kg
Exposure=
0.000062
mg/
kg
(from
EPA
assessment
without
poultry)
10kg
child,
1
liter
consumption
Chronic
DWLOC
is
99
ppb
50
Aventis
and
NAWQA
monitoring
data
averages
are
significantly
less
than
the
maximum
values
of
0.16
ppb
and
5
ppb
numbers
cited
above.
There
are
no
populations
of
concern
for
aggregate
exposure
to
food
and
water
for
carbaryl.
51
Part
III
Residue
Chemistry
Considerations
Line
by
Line
Review
of
the
Residue
Chemistry
Information
Included
in
the
Human
Health
Risk
Assessment
Document
for
Carbaryl
(June
19,
2001)
1.08
Data
Needs/
Label
Requirements
Product
Chemistry
Data
Gaps
Page
95
Paragraph
3
Line
1
3
EPA
comment:
A
review
of
the
labels
and
supporting
residue
data
indicate
that
several
label
amendments
are
required.
Details
are
provided
in
the
Product
and
Residue
Chemistry
Chapters
(DP
Barcode:
D238151)
dated
October
17,
2000.
Aventis
response:
Most
of
these
label
amendments
have
already
been
made
and
approved
by
the
EPA.
See
detailed
information
in
the
review
of
the
Residue
Chemistry
Chapter
below.
Page
96
Paragraph
7
Lines
1
2
EPA
comment:
Adequate
residue
data
are
available
on
olives
provided
that
use
directions
for
olives
are
amended
to
remove
the
statement
allowing
the
use
of
summer
oil
as
an
adjuvant.
Aventis
response:
The
statement
allowing
the
use
of
summer
oil
as
an
adjuvant
has
already
been
deleted
from
the
use
directions
for
olives.
Page:
97
Paragraph:
2
Line
1
EPA
comment:
Additional
data
are
required
depicting
carbaryl
residue
in/
on
cotton
gin
byproducts.
Aventis
response:
Aventis
is
not
supporting
the
cotton
use
and
has
removed
this
crop
from
the
labels.
Aventis
CropScience
requested
cancellation
of
this
use
in
a
letter
to
Mr.
George
Tompkins,
RD,
on
January
22,
1999.
A
Federal
Register
Notice
dated
April
14,
1999
announced
receipt
by
the
Agency
of
an
application
from
RhonePoulenc
Ag
Company
(now
Aventis
CropScience)
to
cancel
the
use
of
carbaryl
products
on
cotton.
52
Page:
97
Paragraph:
3
Lines
1
4
EPA
comment:
The
registrant
does
not
intend
to
support
carbaryl
on
avocados,
barley,
maple
sap,
oats,
rye,
and
sweet
sorghum;
however,
IR
4
has
indicated
(correspondence
from
K.
Dorschner,
IR
4
Project,
9/
15/
94)
that
they
may
fulfill
the
residue
data
requirements
for
some
of
these
commodities.
These
data
have
not
been
submitted.
Aventis
response:
IR
4
has
not
generated
the
residue
data
necessary
to
support
these
uses.
Aventis
CropScience
will
not
support
these
uses.
Page:
97
Paragraph:
4
Lines
1
2
EPA
comment:
The
reregistration
requirements
for
magnitude
of
the
residue
in
livestock
commodities
are
not
fulfilled.
Additional
data
are
required
to
support
dermal
and
poultry
house
uses.
Aventis
response:
Aventis
CropScience
will
neither
support
dermal
nor
poultry
house
uses
of
carbaryl.
A
request
for
cancellation
of
these
uses
in
accordance
with
section
6(
f)(
1)
of
the
Federal
Insecticide,
Fungicide
and
Rodenticide
Act
(FIFRA)
will
be
submitted
shortly
to
the
Agency.
53
Line
by
Line
Review
of
the
Supporting
Document
"Product
and
Residue
Chemistry
Chapters
for
the
Reregistration
Eligibility
Decision
(Felecia
Fort;
November
14,
2000)"
Cover
Memo
Residue
Chemistry
Page
2
Paragraph
3
1
st
Bullet
Pont
EPA
comment:
A
review
of
the
labels
and
supporting
residue
data
indicate
that
several
label
amendments
are
required.
Aventis
response:
Most
of
these
label
amendments
have
already
been
made
and
approved
by
the
EPA.
Page
3
6
th
Bullet
Point
Lines
1
2
EPA
comment:
Adequate
residue
data
are
available
on
olives
provided
that
use
directions
for
olives
are
amended
to
remove
the
statement
allowing
the
use
of
summer
oil
as
an
adjuvant.
Aventis
response:
The
statement
allowing
the
use
of
summer
oil
as
an
adjuvant
has
already
been
deleted
from
the
use
directions
for
olives.
Page:
4
1
st
Bullet
Point
Line
1
EPA
comment:
Additional
data
are
required
depicting
carbaryl
residue
in/
on
cotton
gin
byproducts.
Aventis
response:
Aventis
is
not
supporting
the
cotton
use
and
has
removed
this
crop
from
the
labels.
Aventis
CropScience
requested
cancellation
of
this
use
in
a
letter
to
Mr.
George
Tompkins,
RD,
on
January
22,
1999.
A
Federal
Register
Notice
dated
April
14,
1999
announced
receipt
by
the
Agency
of
an
application
from
RhonePoulenc
Ag
Company
(now
Aventis
CropScience)
to
cancel
the
use
of
carbaryl
products
on
cotton.
Page:
4
2
nd
Bullet
Point
Lines
1
4
EPA
comment:
The
registrant
does
not
intend
to
support
carbaryl
on
avocados,
barley,
maple
sap,
oats,
rye,
and
sweet
sorghum;
however,
IR
4
has
indicated
(Correspondence
from
K.
Dorschner,
IR
4
Project,
9/
15/
94)
that
they
may
fulfill
the
residue
data
requirements
for
some
of
these
commodities.
These
data
have
not
been
submitted.
54
Aventis
response:
IR
4
has
not
generated
the
residue
data
necessary
to
support
these
uses.
Aventis
CropScience
will
not
support
these
uses.
Page:
4
3
rd
Bullet
Point
Lines
1
2
EPA
comment:
The
reregistration
requirements
for
magnitude
of
the
residue
in
livestock
commodities
are
not
fulfilled.
Additional
data
are
required
to
support
dermal
and
poultry
house
uses.
Aventis
response:
Aventis
CropScience
will
neither
support
dermal
nor
poultry
house
uses
of
carbaryl.
A
request
for
cancellation
of
these
uses
in
accordance
with
section
6(
f)(
1)
of
the
Federal
Insecticide,
Fungicide
and
Rodenticide
Act
(FIFRA)
will
be
submitted
shortly
to
the
Agency.
Residue
Chemistry
Chapter
of
the
Reregistration
Eligibility
Decision
(RED)
Document
Residue
Chemistry
Considerations
Summary
of
Science
Findings
Page
3
Table
A1.
Carbaryl
EPs
with
Food/
Feed
Uses
Registered
to
Aventis
Ag
Company
EPA
comment:
Label
acceptance
dates
for
Carbaryl
EPs
are
listed
Aventis
response:
Label
acceptance
dates
listed
for
certain
products
are
incorrect.
Acceptance
dates
of
the
most
recently
EPA
approved
labels
for
SEVIN®
80S,
SEVIN®
5%
Bait,
SEVIN®
XLR
PLUS,
SEVIN®
RP2,
SEVIN®
RP4,
SEVIN®
4F,
and
SEVIN®
80WSP
are
listed
below.
EPA
Reg.
No.
Corrected
Label
Acceptance
Date
Product
Name
264
316
1/
13/
2000
Notification
7/
26/
2001
SEVIN®
brand
80S
Carbaryl
Insecticide
264
320
6/
11/
1999
SEVIN®
brand
5%
Bait
Carbaryl
Insecticide
264
333
2/
8/
2001
SEVIN®
brand
XLR
Carbaryl
Insecticide
(Alternate
brand
name:
SEVIN®
brand
XLR
PLUS
Carbaryl
Insecticide)
264
334
Notification
10/
29/
1999
SEVIN®
brand
RP2
Carbaryl
Insecticide
264
335
10/
18/
2000
SEVIN®
brand
RP4
Carbaryl
Insecticide
264
349
1/
13/
2000
SEVIN®
brand
4F
Carbaryl
Insecticide
55
264
526
4/
12/
2000
SEVIN®
brand
80
WSP
Carbaryl
Insecticide
The
following
SLN
Nos
are
no
longer
active:
SEVIN®
brand
50W:
CA830007,
NC820007
SEVIN®
brand
80S:
CA8300007,
WA900013
SEVIN®
brand
XLR:
NC960003,
OH960003,
OR950006,
PA960002,
VA950001,
WA940021
SEVIN®
brand
4F:
FL890037
Page
3
Paragraph
2
Lines
1
2
EPA
comment:
Use
directions
for
sugar
beets
on
all
labels
should
be
amended
to
specify
a
maximum
of
two
applications
at
a
maximum
single
application
rate
of
1.5
lb
ai/
A
and
a
28
day
PHI.
Aventis
response:
This
change
has
been
made
on
all
Aventis
CropScience
product
labels.
Page
3
Paragraph
3
Lines
1
2
EPA
comment:
Use
directions
for
sweet
corn
on
the
G
formulations
should
be
amended
to
specify
a
48
day
PHI
for
stover.
Aventis
response:
This
change
has
been
made.
Page
3
Paragraph
4
Lines
1
2
EPA
comment:
As
the
registrant
is
no
longer
supporting
uses
on
avocado,
the
SLN
labeling
(CA83007)
for
use
of
carbary
(sic)
on
avocados
in
CA
should
be
revoked.
Aventis
response:
This
SLN
label
has
been
canceled.
Page
3
Paragraph
5
Line
1
EPA
comment:
Use
directions
for
cotton
on
all
labels
should
be
amended
to
remove
the
14
day
PHI
for
forage.
Aventis
response:
The
use
of
carbaryl
products
on
cotton
has
been
canceled.
56
Page
4
Paragraph
1
Lines
1
3
EPA
comment:
Based
on
acceptable
residue
data
on
okra
from
IR
4,
the
registrant
should
amend
use
directions
on
FIC
and
WP
labels
to
specify
a
maximum
or
four
applications
per
season
at
1.5
lb
ai/
A/
application
at
a
minimum
re
treatment
interval
(RTI)
of
6
days
and
a
minimum
PHI
of
3
days.
Aventis
response:
The
current
labels
allow
the
application
of
1
to
1.5
lb.
ai/
A
on
a
6
to
8
day
interval.
A
maximum
of
6
lb
ai/
A
may
be
applied
per
season
with
a
PHI
of
3
days.
Page
4
Paragraph
2
Lines
1
2
EPA
comment:
Use
directions
for
olives
on
all
labels
should
be
amended
to
remove
the
statement
allowing
the
use
of
a
tank
mix
with
summer
oil.
Aventis
response:
This
change
has
been
made
on
all
Aventis
CropScience
product
labels.
Page
4
Paragraph
3
Lines
1
3
EPA
comment:
Based
on
acceptable
residue
data
on
prickly
pear
cactus
from
IR
4,
the
registrant
should
amend
use
directions
on
FIC
and
WP
labels
to
specify
a
maximum
of
three
applications
per
season
at
2
lb
ai/
A/
application
at
a
minimum
RTI
of
7
days
and
a
minimum
PHI
of
3
days.
Aventis
response:
The
current
labels
allow
the
application
of
2
lb
ai/
A
on
a
7
to
10
day
interval.
A
maximum
of
6
lb
ai/
A
may
be
applied
per
season
with
a
PHI
of
3
days.
GLN
860.1300:
Nature
of
the
Residue
Livestock
Page
5
Paragraph
4
Lines
2
6
EPA
comment:
The
registrant
has
stated
its
intention
to
support
dermal
uses
on
poultry
and
carbaryl
uses
in
poultry
houses
and,
according
to
REFS,
these
uses
are
on
carbaryl
labels.
If
the
registrant
intends
to
support
these
uses
of
carbaryl
on
poultry,
tolerances,
supported
by
adequate
metabolism
and
magnitude
of
the
residue
data,
will
be
required,
at
levels
appropriate
for
these
uses.
Aventis
response:
Aventis
CropScience
will
no
longer
support
the
use
of
carbaryl
for
direct
application
to
poultry,
as
well
as
the
poultry
quarters
treatment.
We
will
submit
a
request
for
cancellation
of
these
uses
in
accordance
with
section
6(
f)(
1)
of
the
Federal
Insecticide,
Fungicide
and
Rodenticide
Act
(FIFRA).
57
GLN
860.1500:
Crop
Field
Trials
Page
9
Paragraph
2
Lines
1
3
EPA
comment:
Adequate
data
are
available
to
reassess
the
tolerances
for
residues
of
carbaryl
in/
on
sugar
beet
roots
and
tops
provided
that
use
directions
on
five
currently
approved
labels
are
modified
to
allow
a
maximum
of
two
applications
per
season
at
1.5
lb
ai/
A/
application
and
a
PHI
of
28
days
Aventis
response:
The
labels
were
amended
to
conform
to
these
requirements.
Page
10
Paragraph
3
Lines
1
2
EPA
comment:
Adequate
data
are
available
on
olives
provided
that
use
directions
for
olives
are
amended
to
remove
the
statement
allowing
the
use
of
summer
oil
as
an
adjuvant.
Aventis
response:
The
labels
were
amended
to
conform
to
this
requirement.
Page:
10
Paragraph
5
Lines
2
3
EPA
comment:
Additional
data
are
required
depicting
carbaryl
residue
in/
on
cotton
gin
byproducts.
Aventis
response:
Aventis
is
not
supporting
the
cotton
use
and
has
removed
this
crop
from
the
labels.
Page:
10
Paragraph
6
Lines
1
4
EPA
comment:
The
registrant
does
not
intend
to
support
carbaryl
on
avocados,
barley,
maple
sap,
oats,
rye,
and
sweet
sorghum;
however,
IR
4
has
indicated
(correspondence
from
K.
Dorschner,
IR
4
Project,
9/
15/
94)
that
they
may
fulfill
the
residue
data
requirements
for
some
of
these
commodities.
These
data
have
not
been
submitted.
Aventis
response:
IR
4
has
not
generated
the
residue
data
necessary
to
support
these
uses.
Aventis
CropScience
will
not
support
these
uses.
Table
A2.
Food/
Feed
Use
Patterns
on
EP
Labels
Subject
to
Reregistration
for
Carbaryl
(Case
0080)
Page:
16
EPA
comment:
58
Maximum
Single
Application
Rate,
ai:
3.0
lb/
A
&
4.0
lb/
A
(CA
only).
Aventis
response:
Maximum
Single
Application
Rate,
ai:
3.0
lb/
A
&
4.0
lb/
A
(CA
only).
An
additional
application
at
the
dormant
or
delayed
dormant
timing
may
be
made
at
a
maximum
rate
of
5
lb/
A.
Page:
21
Site:
Beet,
Sugar
EPA
comment:
The
maximum
seasonal
rate
for
sugar
beets
is
4.0
lb
ai/
A.
Aventis
response:
The
rate
for
the
80
WSP
is
4.0
lb
ai/
A.
however,
the
maximum
seasonal
rate
for
flowable
formulations
to
sugar
beets
is
3.0
lb
ai/
A.
Page:
23
Site:
Broccoli,
Brussels
sprouts,
etc.
EPA
comment:
The
preharvest
interval
for
broccoli,
Brussel
sprouts,
cabbage,
cauliflower,
Chinese
cabbage,
collards,
kale,
kohlrabi,
and
mustard
greens
is
3
days.
Aventis
response:
The
preharvest
interval
for
broccoli,
Brussel
sprouts,
cabbage,
cauliflower,
and
kohlrabi
is
3
days.
The
preharvest
interval
for
Chinese
cabbage,
collards,
kale,
and
mustard
greens
is
14
days.
Page:
26
Site:
Citrus
fruits
EPA
comment:
The
maximum
seasonal
rate
to
Citrus
Fruits
in
CA
is
20.0
lbs/
A
Aventis
response:
The
maximum
seasonal
rate
to
Citrus
Fruits
in
CA
is
16.0
lbs/
A
59
Part
IV
Occupational
and
Residential
Exposure/
Risk
Assessment
Line
by
Line
Review
of
the
Supporting
Document
"Carbaryl:
Occupational
and
Residential
Exposure
Assessment
and
Recommendations
for
the
Reregistration
Eligibility
Decision
Document
(Jeffrey
L.
aDawson;
June
28,
2001)"
1.0
Occupational
and
Residential
Exposure/
Risk
Assessment
1.3
Summary
of
Hazard
Concerns
Page:
12
Table
1:
EPA
comment:
UF
column
for
short
term
dermal,
inhalation
&
non
dietary
ingestion
reads
"3000
for
residential
and
300
for
occupational"
Aventis
response:
This
box
should
read,
"3000
for
residential
and
300
for
occupational,+
dermal
absorption
factor"
for
consistency
purposes.
However,
for
the
reasons
previously
stated
the
extra
10X
and
3X
MOS
factors
should
be
removed
due
to
the
recently
submitted
toxicological
studies.
EPA
comment:
UF
column
for
intermediate
term
dermal,
inhalation
&
non
dietary
ingestion
reads
"1000
for
residential
and
100
for
occupational"
and
the
Type
of
Exposure
column
refers
only
to
dermal
exposure.
Aventis
response:
The
UF
box
should
read,
"1000
for
residential
and
100
for
occupational,+
dermal
absorption
factor"
for
consistency
purposes.
The
1000X
MOS
factor
should
be
reduced
as
the
extra
10X
MOS
is
no
longer
necessary.
In
addition,
the
Type
of
Exposure
box
should
read
"Intermediate
term
dermal,
inhalation,
&
non
dietary
ingestion"
for
accuracy.
2.0
Occupational
Exposures
and
Risk
2.1.2
Data
and
Assumptions
for
Handler
Exposure
Scenarios
Occupational
Handler
Exposure
Studies
Page:
34
Paragraph:
3
Note
to
Chemical
Review
Managers:
EPA
comment:
"
There
are
no
data
compensation
issues
associated
with
the
use
of
…the
propoxur
trigger
sprayer
study
has
a
signed
PHED
data
waiver
but
just
has
not
been
included
into
PHED
at
this
time.
60
Aventis
response:
Although
Bayer
has
submitted
a
data
compensation
waiver
for
the
inclusion
of
the
propoxur
study
in
PHED,
the
data
compensation
waiver
is
applicable
only
to
the
data
cited
once
in
PHED.
Specifically,
the
first
paragraph
of
the
data
compensation
waiver
form
states,
`The
following
pertains
only
to
those
data
taken
from
company
studies
and
incorporated
into
the
generic
exposure
monitoring
database'.
In
addition,
the
29
December
1986
memorandum
from
Douglas
Campt,
Director
of
OPP
to
pesticide
registrants
regarding
the
formation
of
PHED,
specifically
states
on
page
2,
bullet
point
1
Those
companies
who
submit
data
for
inclusion
in
the
data
base
will
waive
their
compensation
rights
under
FIFRA
to
the
data
when
referenced
generically
as
part
of
the
data
base.
However,
existing
compensation
rights
will
apply
when
a
company's
data
is
cited
specifically.
Aventis
concludes
that
the
specific
referencing
of
the
Bayer
propoxur
exposure
study
rather
than
a
PHED
generic
study
number
does
not
eliminate
the
data
compensation
rights
of
Bayer.
Aventis
believes
that
the
Health
Effects
Division
should
seek
specific
guidance
from
the
Office
of
General
Counsel
regarding
the
data
compensation
status
of
the
propoxur
study
for
use
in
the
carbaryl
RED.
2.0
Occupational
Exposures
and
Risk
2.1.2
Data
and
Assumptions
for
Handler
Exposure
Scenarios
Page:
32
Paragraph:
First
bullet
Line
2:
EPA
comment:
If
additional
information
such
as
average
or
typical
rates
are
available,
these
values
are
used
as
well
in
order
to
allow
risk
managers
to
make
a
more
informed
risk
management
decision.
Average
application
rates
were
available
from
the
SMART
meeting
and
BEAD's
QUA.
These
data
indicate
that
in
most
cases,
average
application
rates
differ
from
maximum
application
rates
on
average
by
a
factor
of
two.
For
example,
when
interpreting
the
results
of
the
cancer
assessment,
the
small
differences
generally
seen
in
the
available
rates
should
be
considered
along
with
the
overall
magnitude
of
the
cancer
risk
results.
Aventis
response:
Aventis
believes
that
the
average
or
typical
application
rates
provided
in
the
document
should
be
used
in
the
determination
of
intermediate
term,
chronic,
and
cancer
risk
assessments.
The
use
of
the
label
maximum
application
rates
for
each
application
becomes
extremely
unlikely
for
intermediate
term
grower
exposure
assessments
of
10
applications,
commercial
intermediate
term
assessments
of
30
applications,
and
chronic
or
cancer
risk
assessments.
Although
the
Agency
may
believe
it
is
obligated
to
look
at
the
maximum
application
rates
for
exposure
durations
longer
than
the
short
term
assessments,
it
should
as
it
states
provide
61
estimates
of
risk
based
on
average
application
rates
for
the
intermediate
term
and
longer
risk
assessments.
Appendix
C
provides
and
utilizes
only
label
maximum
application
rates
for
the
estimation
of
intermediate
term
and
chronic
MOEs
in
Tables
3,
4,
5,
6,
8,
9,
10,
and
11.
The
risk
assessment
must
provide
MOEs
based
on
average
application
rates
to
allow
risk
managers
to
make
a
more
informed
risk
management
decision.
2.0
Occupational
Exposures
and
Risk
2.1.2
Data
and
Assumptions
for
Handler
Exposure
Scenarios
Page:
42
Table
9:
EPA
comment:
LCO
Turfgun
exposure
estimates
obtained
from
ORETF
study
OMA002
are
based
on
the
wettable
powder
formulation
data.
The
dermal
exposure
estimates
are
0.99
mg/
lb
a.
i.,
0.72
mg/
lb
a.
i.,
and
0.38
mg/
lb
a.
i.
for
single
layer
no
gloves,
single
layer
gloves,
and
double
layer
gloves
clothing
scenarios,
respectively.
Inhalation
exposure
is
0.062
mg/
lb
a.
i.
The
Table
9
footnote
states
WP
formulation
used
for
turfgun
assessment
as
the
unit
exposures
for
this
scenario
were
slightly
higher
than
for
the
other
formulations
(i.
e.,
well
within
a
factor
of
2).
Aventis
response:
Sevin
is
sold
to
the
professional
lawn
care
market
as
either
an
80S
in
water
soluble
packaging
or
as
the
SL
liquid
formulation.
Therefore,
the
use
of
the
wettable
powder
formulation
is
not
appropriate.
Therefore,
the
dermal
exposure
for
the
single
layer
of
clothing
and
glove
scenario
should
be
0.66
mg/
lb
a.
i.
based
on
all
formulations
and
the
inhalation
exposure
should
be
0.007
mg/
lb
a.
i.
based
on
the
higher
water
soluble
packaging
estimate
compared
to
the
flowable
liquid
inhalation
exposure
estimate
of
0.002
mg/
lb
a.
i.
2.3
Occupational
Risk
Characterization
2.3.1
Handler
Characterization
Page:
103
Paragraph:
2
Line:
19
EPA
comment:
Where
available,
average
use
rates
were
also
used
to
provide
for
a
more
informed
risk
management
decision
Aventis
response:
While
Aventis
agrees
that
average
use
rates
should
be
used
for
intermediate
term
and
longer
repeated
exposure
risk
assessments,
the
use
of
average
application
rates
in
the
exposure
assessments
does
not
appear
evident.
The
MOEs
presented
for
intermediate
term
and
longer
risk
are
based
on
label
maximum
application
rates.
The
position
of
Aventis
is
that
handler
MOEs
for
intermediate
term
and
62
longer
risk
assessments
should
be
based
on
average
application
rates
and
not
label
maximum
rates
as
presented
in
the
assessment.
3.0
Residential
and
Other
Non
Occupational
Exposures
and
Risks
3.1.1
Handler
Exposure
Scenarios
Page:
116
Table
27:
EPA
comment:
Table
27
states
that
Hose
end
sprayer
data
for
mix
your
own
(not
the
locking/
no
contact
package)
considered.
Aventis
response:
The
dermal
and
inhalation
exposure
estimates
of
2.61
mg/
lb
a.
i.
and
0.010
mg/
lb
a.
i.,
respectively,
for
the
ready
to
use
(RTU)
hose
end
sprayer
need
to
be
included
in
the
handler
exposure
scenario
estimations
of
homeowner
exposure
during
application
to
lawns.
The
use
of
the
product
in
this
packaging
results
in
exposure
estimates
that
are
different
than
the
dial
type
sprayer
(DTS).
Because
the
RTU
sprayer
is
a
significant
method
of
lawn
application,
the
consideration
of
the
potential
exposure
and
risk
for
lawn
applications
with
the
RTU
sprayer
need
to
be
presented
and
discussed
in
the
risk
assessment.
The
difference
in
exposure
potential
between
the
DTS
and
RTU
hose
end
sprayers
may
provide
important
information
for
risk
management
decisions
that
are
currently
lacking.
3.0
Residential
and
Other
Non
Occupational
Exposures
and
Risks
3.1.3
Residential
Handler
Exposure
and
Non
Cancer
Risk
Estimates
Page:
122
Table
28:
EPA
comment:
Scenario
3,
Fire
Ant
MOEs
are
based
on
the
use
of
100
gallons
or
0.75
lb
a.
i./
event
for
the
garden
vegetable
hose
end
spray
scenario
and
5
gallons
or
0.0375
lb
a.
i./
event
for
garden
low
pressure
handwand
applications.
Aventis
response:
Aventis
does
not
understand
why
there
is
a
20
fold
difference
in
the
amount
of
active
ingredient
handled
between
the
hose
end
sprayer
and
hand
wand
application
of
carbaryl
to
control
fire
ants
at
the
same
site,
gardens.
Aventis
believes
that
the
use
of
0.0375
lb
a.
i./
event
is
reasonable
for
a
vegetable
garden
and
that
the
use
of
100
gallons
of
spray
or
0.75
lb
a.
i./
A
is
more
representative
of
a
lawn
spot
application
to
control
fire
ants.
Scenario
3,
Fire
ant
vegetable
garden
use
should
be
reduced
to
0.075
lb
a.
i./
event,
which
is
similar
to
the
other
scenario
3
vegetable
garden
uses
and
consistent
with
the
fire
ant
control
in
vegetable
gardens
using
the
low
pressure
hand
wand
equipment.
Any
estimation
of
fire
ant
63
control
on
the
lawn
should
be
based
on
exposure
data
from
the
ORETF
hose
end
sprayer
exposure
study
(OMA004)
and
not
from
the
carbaryl
vegetable
garden
exposure
study
(MRID
44459801).
3.0
Residential
and
Other
Non
Occupational
Exposures
and
Risks
3.1.4
Residential
Handler
Exposure
and
Risk
Estimates
for
Cancer
Page:
128
Table
29:
EPA
comment:
Presentation
of
cancer
risks
to
three
significant
figures.
Aventis
response:
Aventis
does
not
believe
that
the
expression
of
cancer
risks
to
three
significant
figures
accurately
portrays
the
lack
of
precision
in
the
risk
assessment.
Cancer
risks
should
be
presented
as
either
one
or
two
significant
figures,
consistent
with
HED
policy.
The
use
of
three
significant
figures
is
leading
to
the
portrayal
of
cancer
risks
such
as
1.08
x
10
6
for
fire
ants
or
1.24
x
10
6
for
vegetable
garden
dusts
as
being
in
excess
of
the
1
x
10
6
guideline.
Both
of
these
risks
are
more
correctly
presented
as
1
x
10
6
to
present
the
lack
of
precision
in
the
cancer
risk
assessment.
Appendix
F:
Carbaryl
Residential
Handler
Exposure
Data
Table
2.
Input
Parameters
for
Carbaryl
Homeowner
Handler
Exposure
and
Risk
Calculations
EPA
comment:
Inhalation
unit
exposures
are
estimated
based
on
a
breathing
volume
of
29
l/
min.
Aventis
response:
The
recommended
breathing
volume
for
adult
short
term
exposure
is
1.0
m
3
/hr
or
17
l/
min
for
light
activities
(U.
S.
EPA
Exposure
Factors
Handbook,
Volume
1
General
Factors,
EPA/
600/
P
95/
002Fa).
In
discussions
between
the
ORETF
and
the
regulatory
advisory
board
to
ORETF,
it
was
agreed
that
application
of
home
pesticide
products
constituted
light
activities
and
that
the
17
l/
min
breathing
rate
will
be
used.
The
29
l/
min
rate
used
by
HED
is
the
PHED
default
and
represents
agricultural
work
practices
that
are
more
strenuous
than
home
pesticide
application.
Therefore,
all
residential
inhalation
exposure
estimates
should
be
based
on
17
l/
min
breathing
volume
or
59%
of
the
inhalation
exposure
estimates
presented
in
the
HED
assessment.
64
Part
IV
Occupational
and
Residential
Exposure/
Risk
Assessment
SUPPORTING
DISCUSSION
Occupational
and
Residential
Exposure
Assessment
The
assessment
of
occupational
and
residential
exposure
and
risk
prepared
by
Mr.
Jeff
Dawson
was
a
comprehensive
assessment
of
excellent
quality.
This
is
reflected
by
the
relatively
minimal
number
of
factual
error
comments
provided
by
Aventis
CropScience.
Based
on
the
quality
of
the
initial
assessment,
the
major
effort
regarding
the
assessment
of
occupational
and
residential
exposure
to
carbaryl
will
involve
refinement
of
the
risk
assessment.
Aventis
CropScience
has
conducted,
or
is
in
the
process
of
conducting,
studies
relevant
to
the
refinement
of
the
occupational
and
residential
risk
assessment.
These
studies
are
as
follows:
4
Week
Repeated
Dose
Dermal
Toxicity
Study
with
Sevin
XLR
Plus
in
Rats.
The
study
is
completed
and
a
draft
report
is
currently
in
review
by
Aventis.
The
results
of
this
study
are
intended
to
replace
the
current
dermal
exposure
toxicity
endpoints
based
on
oral
toxicity
used
for
short
term
and
intermediate
term
occupational
and
residential
handler
exposure
when
handling
liquid
formulations
of
carbaryl.
Expected
completion
date:
September
2001
4
Week
Repeated
Dose
Dermal
Toxicity
Study
with
Sevin
80S
in
Rats.
The
study
is
completed
and
a
draft
report
is
currently
in
review
by
Aventis.
The
results
of
this
study
are
intended
to
replace
the
current
dermal
exposure
toxicity
endpoints
based
on
oral
toxicity
used
for
short
term
and
intermediate
term
occupational
and
residential
handler
exposure
when
handling
solid
formulations
of
carbaryl.
Expected
completion
date:
September
2001
4
Week
Repeated
Dose
Dermal
Toxicity
Study
with
Carbaryl
Technical
in
Rats.
The
study
is
completed
and
a
draft
report
is
currently
in
review
by
Aventis.
The
results
of
this
study
are
intended
to
replace
the
current
dermal
exposure
toxicity
endpoints
based
on
oral
toxicity
used
for
short
term
and
intermediate
term
occupational
and
residential
postapplication
dermal
exposure.
Expected
completion
date:
September
2001
Measurement
of
Pesticide
Exposure
of
Suburban
Residents
Associated
with
the
Residential
Use
of
Carbaryl.
This
is
an
ongoing
biological
monitoring
study
of
10
families
in
California
and
10
families
in
Missouri.
The
study
will
monitor
the
absorbed
dose
of
carbaryl
resulting
from
a
lawn
broadcast
application
and
subsequent
vegetable
garden
application
of
carbaryl
by
an
adult
family
member.
Postapplication
absorbed
dose
of
all
adults
and
children
aged
four
to
seventeen
will
be
followed
over
a
three
day
period.
The
participants'
postapplication
activities
will
be
recorded
but
not
controlled
to
establish
a
range
of
absorbed
65
doses.
The
data
will
be
used
along
with
the
residential
exposure
assessment
to
improve
understanding
of
residential
exposure
to
carbaryl.
Expected
completion
date:
March
2002
University
of
California
Riverside
biological
monitoring
of
citrus
orchard
application
and
postapplication
apple
thinning
and
cherry
harvesting
job
functions
is
completed
in
the
field.
The
results
from
these
studies
will
be
used
to
refine
the
PHED
and
ARTF
based
exposure
estimates.
These
are
high
exposure
potential
work
functions
and
the
biological
monitoring
data
are
intended
to
refine
the
assessments
of
these
work
functions.
Expected
completion
date:
March
2002
66
APPENDIX
I
Business
Confidential
Surface
Water
Monitoring
for
Residues
of
Carbaryl
in
High
Use
Areas
of
the
United
States
(Stone
Environmental,
Inc.
Report
#99
1005
F)
(hard
copy
provided)
1
CARBARYL
PC
Code
No.
056801;
Case
0080
Review
of
the
Draft
Environmental
Fate
and
Ecological
Risk
Assessment
for
the
Reregistration
of
Carbaryl
August
6,
2001
Aventis
CropScience
P.
O.
Box
12014,
2
T.
W.
Alexander
Drive
Research
Triangle
Park,
NC
27709
2
CARBARYL
PC
Code
No.
056801;
Case
0080
Review
of
the
Draft
Environmental
Fate
and
Ecological
Risk
Assessment
for
the
Reregistration
of
Carbaryl
TABLE
OF
CONTENTS
TABLE
OF
CONTENTS
...............................................................................................................
2
GENERAL
COMMENTS
....................................................................................................................
5
TRANSMITTAL
DOCUMENT
............................................................................................................
9
Data
Gaps
...............................................................................................................................
9
Environmental
Fate
and
Transport
...............................................................................
9
Water
Resources
...........................................................................................................
9
Ecological
Effects
Data
requirement
..........................................................................
10
Label
Information
.......................................................................................................
11
DRAFT
RED
DOCUMENT
..............................................................................................................
13
1.0
Summary
and
Environmental
Risk
Conclusions
...........................................................
13
Risk
to
Terrestrial
Organisms
.....................................................................................
13
Fate
and
Water
Assessment
........................................................................................
13
2.0
Introduction
....................................................................................................................
14
3.0
Integrated
Risk
Characterization
...................................................................................
15
Introduction
.................................................................................................................
15
Aquatic
Organisms
......................................................................................................
15
Terrestrial
Organisms
.................................................................................................
16
Endocrine
Disruption
Concerns
..................................................................................
18
Uncertainties
...............................................................................................................
19
4.0
Environmental
Fate
Assessment
....................................................................................
20
Exposure
Characterization
..........................................................................................
20
Persistence
....................................................................................................
23
Mobility
........................................................................................................
24
Field
Dissipation
...........................................................................................
25
Foliar
Dissipation
.........................................................................................
27
Atmospheric
Transport
.................................................................................
28
1
Naphthol
Fate
and
Transport
.....................................................................
28
Aquatic
Exposure
Assessment
....................................................................................
30
Surface
Water
...............................................................................................
30
Estimated
Environmental
Concentrations
for
Terrestrial
Ecological
Risk
Assessment32
5.0
Drinking
Water
Assessment
..........................................................................................
32
Water
Resources
Assessment
.....................................................................................
32
Drinking
Water
Exposure
Assessment
.........................................................
33
Water
Treatment
Effects
..............................................................................
37
Ground
Water
Resources
..............................................................................
38
3
Surface
Water
Resources
..............................................................................
39
6.0
Hazard
and
Risk
Assessment
for
Aquatic
Organisms
..................................................
45
Hazard
assessment
for
Aquatic
organisms
.................................................................
45
Estuarine/
Marine
Fish
..................................................................................
45
Aquatic
Plants
...............................................................................................
45
Risk
Assessment
for
Aquatic
Organisms
....................................................................
45
Estuarine/
Marine
Fish
..................................................................................
46
7.0
Hazard
and
Risk
Assessment
for
Terrestrial
Organisms
..............................................
46
Hazard
Assessment
for
Terrestrial
Organisms
...........................................................
46
Mammalian
...................................................................................................
46
Risk
Assessment
for
Terrestrial
Organisms
................................................................
46
Avian
Risk
....................................................................................................
46
Mammalian
Risk
..........................................................................................
47
Reproduction
Effects
....................................................................................
48
9.0
References
(non
MRID)
...............................................................................................
50
Appendix
A:
Environmental
Fate
Study
Reviews
(DERs)
.................................................
50
Appendix
B:
Refined
Water
Memo
....................................................................................
50
Appendix
C:
Ecological
Risk
Assessment
..........................................................................
51
Toxicity
Endpoints
Used
in
the
Risk
Assessment
......................................................
51
Avian
Acute
and
Chronic
Risk
...................................................................................
51
Risk
from
Exposure
to
Non
granular
Products
...........................................................
52
Risk
from
Exposure
to
Granular
Products
..................................................................
52
Aquatic
Plants
.............................................................................................................
52
Appendix
D:
Toxicity
Assessment
......................................................................................
52
Birds,
Chronic
Toxicity
..............................................................................................
53
Mammals,
Acute
and
Chronic
....................................................................................
53
Freshwater
Fish,
Acute
...............................................................................................
54
Freshwater
Invertebrates,
Acute
.................................................................................
54
Estuarine
and
Marine
Invertebrates,
Acute
.................................................................
54
DISCUSSION
.............................................................................................................................
56
1.
Surface
Water
Concentrations
........................................................................................
56
Summary
of
Registrant
Surface
Water/
Drinking
Water
Monitoring
Program
...........
56
Summary
of
Surface
Water
Data
from
the
NAWQA
Program
..................................
58
Summary
of
Carbaryl
Analytical
Methods
used
in
the
NAWQA
Program
................
60
Gas
Chromatography/
Mass
Spectroscopy
Method
......................................
60
High
Performance
Liquid
Chromatography/
Photodiode
Array
Method
.....
64
Summary
of
Surface
Water
Data
from
the
California
DPR
Surface
Water
Database
64
2.
Ground
Water
Concentrations
........................................................................................
66
Summary
of
Ground
Water
Data
from
the
NAWQA
Program
..................................
66
REFERENCES
............................................................................................................................
68
4
TABLE
OF
CONTENTS
(continued)
Tables
Table
1.
Summary
Of
Results
From
The
Carbaryl
Drinking
Water
Monitoring
Study.
57
Table
2.
Carbaryl
Detections
Reported
In
Pesticides
In
Streams
Update
(Larson,
2001)
...........................................................................................................
58
Table
3.
Frequency
Of
Carbaryl
Detections
By
GC/
MS
In
Different
Concentration
Ranges
Reported
In
The
NAWQA
Database
As
Of
July
16,
2001
............
59
Table
4.
Frequency
Of
Carbaryl
Detections
By
LC/
PDA
In
Different
Concentration
Ranges
Reported
In
The
NAWQA
Database
As
Of
July
16,
2001
............
59
Table
5.
Recovery
And
Precision
For
Multiple
Determinations
Of
Carbaryl
In
GC/
MS
Method
For
Carbaryl
Spiked
In
Different
Water
Samples
............
61
Table
6.
Percent
Recoveries
Of
Carbaryl
Detected
By
The
NAWQA
GC/
MS
Method
In
Laboratory
Control
Spikes
And
Field
Matrix
Spikes
At
A
Spiking
Level
Of
0.1
µ
g/
L
.................................................................................................
63
Table
7.
Recovery
And
Precision
For
Multiple
Determinations
Of
Carbaryl
In
LC/
PDA
Method
For
Carbaryl
Spiked
In
Different
Water
Samples
..........
64
Table
8.
Carbaryl
Detections
Reported
In
California
DPR
Surface
Water
Monitoring
Database
......................................................................................................
65
Table
9.
Limits
Of
Quantification
For
Carbaryl
Analytical
Methods
Reported
In
California
DPR
Surface
Water
Monitoring
Database
.................................
65
Table
10.
Carbaryl
Detections
Reported
In
Pesticides
In
Ground
Water
Update
(Kolpin,
2001)
.............................................................................................
67
Confidential
Business
Attachments
APPENDIX
1
..............................................................................................................................
70
APPENDIX
2
..............................................................................................................................
71
The
last
page
of
this
report
is
number
70
\#
"0"
70.
5
General
Comments
The
EFED
draft
chapter
of
the
carbaryl
RED
is
very
thorough
using
a
wealth
of
references.
The
use
of
published
literature
over
submitted
data
is
significant.
The
quality
of
the
published
literature
is
at
times
at
least
questionable
and
other
times
does
not
fulfill
the
requirements
set
by
EPA
for
studies
submitted
by
the
registrant
(e.
g.
thorough
description
of
test
conditions,
clear
identification
of
the
test
material,
analytical
verification,
GLP
etc.).
Data
of
such
poor
quality
should
not
be
used
as
key
information
in
the
risk
assessment.
For
the
30
day
response
not
all
literature
references
could
be
verified
or
the
quality
ascertained.
There
is
a
high
level
of
redundancy
in
the
document
making
it
difficult
to
read.
Reducing
repetitions
to
a
minimum
would
facilitate
the
reading.
We
believe
it
is
inappropriate
to
include
DERs
in
the
RED
Chapters.
A
summary
of
study
findings
is
already
presented
in
the
document.
DERs
should
be
made
available
to
the
public
through
the
regular
procedure
under
the
Freedom
of
Information
Act
after
they
have
been
reviewed
and
cleared
for
confidential
business
information.
The
use
of
carbaryl
on
barley,
oats,
rye,
cotton,
and
livestock
are
cancelled
.
It
should
be
noted
that
Aventis
CropScience
labels
for
the
technical
materials
and
the
end
use
products
containing
carbaryl
were
amended
to
delete
these
uses.
The
Agency
has
already
approved
the
labeling
changes
(please
refer
to
HED
response
document,
Section
III
for
details).
Aventis
CropScience
will
no
longer
support
the
use
of
carbaryl
on
poultry
(direct
application
and
poultry
quarters
treatment).
We
will
shortly
submit
a
request
for
cancellation
of
these
uses
in
accordance
with
section
6(
f)(
1)
of
the
Federal
Insecticide,
Fungicide
and
Rodenticide
Act
(FIFRA)
(please
refer
to
HED
response
document,
Section
III
for
details).
Aventis
CropScience
is
in
the
process
of
conducting,
or
has
scheduled,
studies
relevant
to
the
refinement
of
the
environmental
risk
assessments
for
carbaryl
and
the
major
degradate
1
naphthol.
These
studies
are
as
follows:
Rate
and
Route
of
Aerobic
Degradation
in
Soils.
These
studies
have
been
initiated
with
parent
carbaryl
applied
to
four
diverse
U.
S.
soils.
The
data
are
intended
to
provide
additional
half
life
determinations
for
parent
carbaryl
and
the
major
degradate
1
naphthol.
Expected
completion
date:
March
2002
Aerobic
Aquatic
Metabolism
in
Two
Water/
Sediment
Systems.
These
studies
have
been
initiated
with
parent
carbaryl
applied
to
two
distinct
U.
S.
water/
sediment
systems.
The
data
are
intended
to
provide
additional
half
life
determinations
for
parent
carbaryl
and
the
major
degradate
1
naphthol.
In
addition,
further
identification
of
additional
degradation
products
is
anticipated.
Expected
completion
date:
March
2002
Adsorption
and
Desorption
of
1
Napthol
to
five
soils.
This
study
has
been
scheduled
to
evaluate
the
adsorption
and
desorption
of
the
major
carbaryl
degradate
to
five
soils/
sediment.
The
data
are
intended
to
provide
information
necessary
to
evaluate
the
6
environmental
risks
from
1
naphthol
in
standard
models.
Expected
completion
date:
March
2002
For
the
reregistration
process
in
the
EU,
Aventis
CropScience
is
in
the
process
of
conducting,
or
has
scheduled,
studies
relevant
to
the
refinement
of
the
ecotoxicological
risk
assessments
for
carbaryl
and
the
major
degradate
1
naphthol.
These
studies
are
as
follows:
Studies
with
Carbaryl:
Acute
oral
LD50
in
mallard
ducks
Dynamic
acute
LC50
in
bluegill
sunfish
Acute
toxicity
in
Daphnia
Acute
toxicity
in
Chironomus
riparius
Toxicity
in
Selenastrum
capricornutum
Acute
oral
and
contact
toxicity
in
honeybees
14
d
toxicity
in
earthworms
Effects
on
soil
microorganisms
(nitrification/
carbon
cycle)
Effect
on
sewage
treatment
Studies
with
1
naphthol
Early
life
stage
study
in
fathead
minnow
Acute
toxicity
in
Daphnia
Acute
toxicity
in
Daphnia
in
presence
of
sediment
Chronic
toxicity
in
Daphnia
14
d
toxicity
in
earthworms
Formulated
Product
Vegetative
Vigor
Toxicity
in
Selenastrum
capricornutum
Acute
oral
and
contact
toxicity
in
honeybees
Effect
on
non
target
arthropods
14
d
toxicity
in
earthworms
Effects
on
soil
microorganisms
(nitrification/
carbon
cycle)
Ecotoxicological
Risk
Assessments
Aventis
has
pointed
out
several
errors
in
the
PRZM
input
parameters
(see
comments
made
to
Tables
5
and
6
of
the
draft
RED),
overly
conservative
estimates
of
foliar
dissipation
half
lives
and
changes
in
ecotoxicology
study
endpoints.
This
indicates
that
a
re
calculation
of
the
EECs
and
risk
quotients
are
warranted
in
a
number
of
instances.
Endocrine
Disruption
Reports
in
the
open
literature
on
the
reproductive
effects
of
carbaryl
in
wild
mammals
are
at
best
ambivalent.
The
recently
submitted
2
generation
study
in
rats
demonstrates
the
absence
of
7
reproductive
effects.
As
EPA
pointed
out,
findings
reported
in
the
literature
were
made
at
concentrations
well
above
the
highest
peak
concentration
modeled.
Therefore
these
findings
are
irrelevant
for
a
risk
assessment
and
at
the
current
stage
of
discussion
about
endocrine
disruption.
If
the
concern
about
the
endocrine
potential
of
carbaryl
persists,
the
issue
should
be
revisited
once
the
Agency's
endocrine
disrupter
screening
and
testing
program
as
well
as
a
policy
on
how
to
incorporate
positive
findings
into
an
ecological
risk
assessment
have
been
fully
developed.
Mobility
The
classification
of
carbaryl
as
mobile
to
very
mobile
is
inconsistent
with
measured
Koc
values
of
177
to
249
(MRID
43259301).
According
to
the
widely
used
classification
scheme
of
McCall,
et
al.
(1980)
wherein
Koc
values
between
150
and
500
denote
medium
mobility
in
soil,
carbaryl
would
be
classified
as
having
medium
mobility
in
most
soils.
This
classification
of
medium
mobility
is
further
supported
by
the
acceptable
column
leaching
study
(MRID
43320701)
in
which
aged
carbaryl
residues
were
only
slightly
mobile
in
a
number
of
soils.
The
mobility
of
carbaryl
would
be
expected
to
be
higher
in
sandy
soils
or
in
soils
of
low
organic
matter.
1
Napthol
Fate
and
Transport
The
Agency
is
requiring
additional
information
on
the
persistence
and
mobility
of
1
naphthol,
a
major
environmental
degradate
of
carbaryl.
However,
a
half
life
for
1
naphthol
of
less
than
1
day
can
be
calculated
from
the
carbaryl
aerobic
soil
metabolism
study
(MRID
42785101).
The
data
from
this
study
demonstrate
that
under
aerobic
soil
conditions
the
formation
and
decline
of
1
naphthol,
starting
from
parent
carbaryl,
is
complete
in
less
than
14
days.
This
half
life
can
be
used
for
preliminary
environmental
fate
modeling
to
estimate
EECs
for
1
naphthol.
The
EPA
suggested
that
1
naphthol
is
not
strongly
sorbed
to
soil.
Additional
information
available
in
the
literature
demonstrates
that
the
sorption
of
1
naphthol
to
soil
is
stronger
than
that
seen
for
carbaryl
itself.
Hassett
et
al.
(1981)
has
demonstrated
that
the
sorption
of
1
naphthol
was
the
result
of
sorption
to
organic
carbon
resulting
in
Koc
values
between
431
and
15,618.
These
data
indicate
that
1
naphthol
is
less
mobile
and
less
susceptible
to
leaching
than
carbaryl
itself,
and
they
demonstrate
that
at
least
a
portion
of
the
1
naphthol
residue
is
tightly
sorbed
to
soil
constituents.
(A
copy
of
this
article
is
being
submitted
with
the
response
to
the
draft
RED.)
To
meet
the
requirement
for
information
on
the
adsorption
and
desorption
of
1
naphthol
by
the
Agency,
the
registrant
is
conducting
an
adsorption/
desorption
study
to
meet
the
163
1
guideline.
Study
results
should
be
available
for
submission
to
the
Agency
in
the
first
quarter
of
the
calendar
year
2002.
Surface
Water/
Drinking
Water
Aventis
disagrees
with
EPA
that
the
modeling
simulations
provide
a
conservative,
though
not
unreasonable,
estimate
on
possible
concentrations
in
drinking
water.
Drinking
water
concentrations
derived
from
PRZM/
EXAMS
greatly
overestimate
the
potential
exposure
to
carbaryl
in
drinking
water,
generally
by
several
orders
of
magnitude.
Results
from
the
drinking
8
water
monitoring
program
conducted
by
the
registrant
provides
a
`real
world'
assessment
of
the
potential
for
human
exposure
to
carbaryl
in
drinking
water
derived
from
surface
water.
Ground
Water
EPA
summarized
information
on
the
detection
of
carbaryl
in
groundwater
from
the
EPA
Pesticides
in
Groundwater
Database,
the
EPA
STORET
database
and
the
NAWQA
database.
Each
of
the
databases
shows
a
pattern
of
very
low
levels
of
carbaryl
detection
in
few
groundwater
resources.
These
analyses
confirm
several
statements
made
by
the
Agency
that
carbaryl
have
limited
potential
to
impact
groundwater
resources.
However,
on
page
2
of
the
Memorandum
issued
June
28,
2001,
in
conjunction
with
the
EFED
RED
chapter
for
carbaryl,
EPA
is
requiring
additional
information
on
"Surface
and
groundwater
monitoring
in
urban
and
suburban
use
areas
(non
guideline)."
Based
on
the
characteristics
of
carbaryl
and
the
available
data
demonstrating
limited
impact
of
carbaryl
on
ground
water
resources,
additional
studies
to
evaluate
the
potential
for
carbaryl
to
contaminate
groundwater
are
unnecessary
and
unwarranted.
9
Line
by
Line
Review
of
the
Carbaryl
EFED
RED
Chapter
Transmittal
Document
Data
Gaps
Environmental
Fate
and
Transport
Page:
2
Paragraph:
1
Line:
1
EPA
comment:
Fate
information
on
the
degradation
product
1
naphthol
is
required.
1.
Mobility
–
adsorption
and
desorption
studies
for
the
1
naphthol
degradate
(163
1)
2.
Persistence
–
aerobic
soil
metabolism
study
on
1
naphthol
Aventis'
response:
Literature
data
(Hassett
et
al.
1981)
on
the
adsorption
of
1
naphthol
are
provided
in
this
response.
Aventis
is
in
the
process
of
conducting
an
additional
adsorption/
desorption
study
on
1
naphthol
and
intends
to
submit
study
data
to
EPA
by
March
2002.
The
degradation
of
1
naphthol
under
aerobic
soil
conditions
has
been
widely
reported
in
the
literature.
Several
citations
are
included
in
the
EPA
draft
RED.
The
half
life
of
1
naphthol
estimated
from
the
acceptable
aerobic
soil
persistence
study
on
carbaryl
(MRID
42785101)
is
less
than
1
day.
Aventis
is
conducting
additional
laboratory
aerobic
soil
degradation
studies
on
carbaryl
that
will
be
used
to
provide
additional
determinations
of
the
half
life
for
the
degradate
1
naphthol
and
satisfy
the
Agency's
requirement
for
data
on
the
persistence
of
1
naphthol.
Aventis
intends
to
submit
these
study
data
to
EPA
by
March
2002.
Water
Resources
Page:
2
Paragraph:
3
and
4
EPA
comment:
"EFED
believes
that
adequate
data
are
available
to
support
the
conclusions
reached
for
carbaryl's
impact
on
surface
water
and
groundwater
quality
with
the
exceptions
noted
below.
Additional
information
is
needed
to
characterize
the
impact
of
the
degradate
1
naphthol
[in]
groundwater
and
surface
water.
Surface
and
groundwater
monitoring
in
urban
and
suburban
use
areas
(non
guideline)"
are
required.
10
Aventis'
response:
The
surface
water
monitoring
program
conducted
by
Aventis
includes
monitoring
in
urban
and
suburban
use
areas.
Aventis
believes
that
the
need
for
information
on
the
degradate
1
naphthol
will
be
satisfied
by
the
aerobic
soil
and
adsorption/
desorption
data
that
will
be
submitted
to
the
Agency.
These
data
can
be
used
to
evaluate
the
availability
of
1
naphthol
using
established
EPA
modeling
guidelines.
The
Agency's
proposed
requirement
for
groundwater
monitoring
is
unnecessary
and
is
addressed
in
Aventis'
response
to
Agency
comments
in
the
draft
RED.
Ecological
Effects
Data
requirement
Page:
2
EPA
comment:
The
ecological
toxicity
database
is
complete
except
for:
6.
Aquatic
Plant
Growth
Guideline
122
2
Aventis'
response:
The
data
requirement
should
be
deleted.
Aquatic
plant
growth
studies
were
submitted
to
the
Agency
in
1992.
An
October
04,
2000
OPP
Guideline
Status
Report
(Chemical
Review
Management
System)
lists
the
guideline
122
2
status
as
"Acceptable/
Satisfied".
The
studies
are:
MRID
No.
Title
Acceptability
Code
42372101
Lintott,
D.
(1992)
Carbaryl
Technical:
Acute
Toxicity
To
The
Freshwater
Blue
Green
Alga,
Anabaena
flos
aquae,
Under
Static
Test
Conditions:
Lab
Project
Number:
J9112004E.
Unpublished
Study
Prepared
By
Toxikon
Environmental
Sciences.
53
P.
June
25,
1992
Upgradable
42372102
Lintott,
D.
(1992)
Carbaryl
Technical:
Acute
Toxicity
To
Duckweed,
Lemna
gibba
G3,
Under
Static
Test
Conditions:
Lab
Project
Number:
J9112004G.
Unpublished
Study
Prepared
By
Toxikon
Environmental
Sciences.
53
P.
January
1,
1992
Upgradable
42372802
Lintott,
D.
(1992)
Carbaryl
Technical:
Acute
Toxicity
To
The
Freshwater
Green
Alga,
Selenastrum
capricornutum
Under
Static
Conditions:
Lab
Project
Number:
J9112004C.
Unpublished
Study
Prepared
By
Toxikon
Environmental
Sciences.
53
P.
June
9,
1992
Acceptable
42431601
Lintott,
D.
(1992)
Carbaryl
Technical:
Acute
Toxicity
To
The
Freshwater
Diatom,
Navicula
pelliculosa,
Under
Static
Test
Conditions:
Lab
Project
Number:
J9112004F.
Unpublished
Study
Prepared
By
Toxikon
Environmental
Sciences.
52
P.
August
10,
1992
Acceptable
42431602
Lintott,
D.
(1992)
Carbaryl
Technical:
Acute
Toxicity
To
The
Saltwater
Diatom,
Skeletonema
costatum,
Under
Static
Test
Conditions:
Lab
Project
Number:
J9112004D.
Unpublished
Study
Prepared
By
Toxikon
Environmental
Sciences.
49
P.
August
10,
1992
Supplemental
11
Page:
2
EPA
comment:
The
ecological
toxicity
database
is
complete
except
for:
7.
Submission
of
a
FETOX
amphibian
toxicity
study
is
required.
Aventis'
response:
The
data
requirement
should
be
deleted.
From
the
published
results
it
is
evident
that
carbaryl
is
practically
non
toxic
to
the
bullfrog.
Effects
in
plain
leopard
frogs
are
reported
at
levels
well
above
environmental
concentrations.
These
results
were
obtained
testing
U.
S.
native
species.
In
the
proposed
FETOX
assay,
a
non
native
species
Xenopus
laevis
is
used.
This
African
species
is
unique
in
its
behavior.
Neither
the
species
nor
the
test
methods
are
suitable
for
ecotoxicological
purposes.
As
the
risk
to
amphibians
can
be
evaluated
from
the
studies
cited,
and
as
the
effects
are
only
at
levels
well
above
the
EEC,
this
study
should
not
be
required.
Label
Information
Page:
3
EPA
comment:
For
terrestrial
and
residential
uses:
1.
"Do
not
apply
directly
to
water,
or
to
areas
where
surface
water
is
present
or
to
intertidal
areas
below
the
mean
high
water
mark.
Do
not
contaminate
water
when
disposing
of
equipment
washwater
or
rinsate."
Aventis'
response:
Similar
language
is
already
present
on
Aventis'
SEVIN®
labels.
Page:
3
EPA
comment:
For
terrestrial
and
residential
uses:
3.
"This
product
may
contaminate
water
through
drift
of
spray
in
wind.
This
product
has
a
high
potential
for
runoff
for
several
days
after
application
after
application
(sic).
Poorly
draining
soils
and
soils
with
shallow
water
tables
are
more
prone
to
produce
runoff
that
contains
this
product.
Household
labels
–
Avoid
applying
this
product
to
ditches,
swales,
and
drainage
ways.
Runoff
of
this
product
will
be
reduced
by
avoiding
applications
when
rainfall
is
forecasted
to
occur
within
48
hours.
Agricultural
Label
–
A
level,
well
maintained
vegetative
buffer
strip
between
areas
to
which
this
product
is
applied
and
surface
water
features
such
as
ponds,
streams,
and
springs
will
reduce
the
potential
for
contamination
of
water
from
rainfall
runoff.
Runoff
of
this
product
will
be
reduced
by
12
avoiding
applications
when
rainfall
is
forecasted
to
occur
within
48
hours."
Aventis'
response:
Aventis
would
like
to
further
discuss
appropriate
label
language
with
the
Agency.
However,
it
should
be
noted
that
light
to
moderate
rainfall
(or
irrigation)
after
application
will
also
help
move
carbaryl
residues
deeper
into
the
soil,
thus
making
them
less
susceptible
to
runoff.
The
language
in
the
last
sentence
should
be
changed
to
read,
"…
when
heavy
rainfall
is….".
Page:
3
EPA
comment:
For
terrestrial
and
residential
uses:
4.
This
pesticide
is
toxic
to
fish
and
aquatic
invertebrates.
Aventis'
response:
Aventis'
SEVIN
labels
currently
state
"This
product
is
extremely
toxic
to
aquatic
and
estuarine
invertebrates."
Page:
3
EPA
comment:
For
terrestrial
and
residential
uses:
5.
This
product
is
highly
toxic
to
bees
exposed
to
direct
treatment
or
residues
on
blooming
crops
or
weeds.
Do
not
apply
this
product
or
allow
it
to
drift
to
blooming
crops
or
weeds
if
bees
are
visiting
the
treatment
area.
Aventis'
response:
Aventis'
SEVIN
labels
currently
contain
similar
language.
13
Draft
RED
Document
1.0
Summary
and
Environmental
Risk
Conclusions
Risk
to
Terrestrial
Organisms
Page:
1
Paragraph:
4
Line:
2
EPA
comment:
As
discussed
in
pp.
44
45
and
in
Appendix
D.
Aventis'
response:
The
mammalian
risk
quotients
are
discussed
on
pages
48
to
50
and
in
Appendix
C,
not
as
described
in
this
text.
Fate
and
Water
Assessment
Page:
3
Paragraph:
5
Line:
3
EPA
comment:
…in
the
U.
S.
G.
S
NAQWA
program.
NAQWA…
Aventis'
response:
The
abbreviation
for
the
U.
S.
G.
S.
program
is
NAWQA
Page:
5
Paragraph:
1
Line:
7
EPA
comment:
…estimate
of
possible
concentrations
drinking
water.
Aventis'
response:
missing
word
–
…concentrations
"in"
drinking…
Page:
5
Paragraph:
4
Line:
4
EPA
comment:
…hydrolyzes
in
neutral
(half
life
=
12
days)
and
alkaline
environments
(pH
9
half
life
=
3.2).
Aventis'
response:
Missing
units
of
after
second
half
life.
The
units
are
hours,
so
"=
3.2
hours)".
Page:
5
Paragraph:
4
Line:
5
EPA
comment:
…photolysis
in
water
with
a
half
life
of
21
days
14
Aventis'
response:
this
is
for
photolysis
in
sterile
water,
not
microbially
active
water,
so
the
phrase
would
be
more
precise
as
"…
photolysis
in
sterile
water…".
Page:
5
Paragraph:
4
Line:
last
EPA
comment:
(Kf
=1.7
to
3.2).
Aventis'
response:
The
upper
value
Kf
for
carbaryl
should
be
listed
as
3.5
as
referenced
by
EPA
elsewhere
(e.
g.
Table
3,
page
20)
in
the
document.
2.0
Introduction
Page:
6
Paragraph:
2
Line:
1
3
EPA
comment:
Carbaryl
(1
naphthyl
N
methylcarbamate)
is
a
broad
spectrum
carbamate
insecticide
and
acaricide
registered
for
control
of
over
300
species
of
insects
and
mites
on
over
100
crop
and
noncrop
use
sites,
including
homeowner
uses;
pet,
poultry,
and
livestock
uses;…
Aventis'
response:
Carbaryl
is
no
longer
registered
for
use
on
livestock.
Aventis
CropScience
will
not
support
the
reregistration
of
the
use
on
poultry
(direct
application
and
poultry
quarters
treatment).
We
will
shortly
submit
a
request
for
cancellation
of
this
use
in
accordance
with
section
6(
f)(
1)
of
the
Federal
Insecticide,
Fungicide
and
Rodenticide
Act
(FIFRA).
Page:
6
Paragraph:
3
Line:
2
3
EPA
comment:
Approximately
2.5
million
pounds
of
carbaryl
are
applied
annually
in
the
U.
S.
A
map
showing
the
widespread
use
of
carbaryl
in
agriculture
is
shown
in
figure
1.
Aventis'
response:
Summation
of
the
data
in
Figure
1
gives
a
total
of
approximately
3.3
million
pounds
of
carbaryl.
Both
the
2.5
and
3.3
million
pound
figures
are
inconsistent
with
the
value
of
4
million
pounds
cited
on
page
35.
The
2.5
million
pounds
is
an
average
of
usage
over
1987
to
1996
developed
in
a
memo
by
Frank
Hernandez,
July
21,
1998.
The
value
of
2.5
million
pounds
in
the
text
should
be
qualified
with
the
additional
information
on
the
fact
that
it
is
an
average
for
usage
over
1987
to
1996
and
is
not
a
value
for
a
single
year.
Page:
7
Paragraph:
1
Line:
3
4
15
EPA
comment:
Carbaryl
is
also
used
extensively
for
residential
and
other
non
agricultural
uses,
being
the
second
most
commonly
insecticide
(sic)
used
in
the
home.
Aventis'
response:
Carbaryl
is
not
registered
for
use
inside
homes.
It
is
registered
for
use
outdoors
in
the
lawn
and
garden
around
homes.
In
addition,
an
evaluation
of
the
Vista
(Triad)
data
for
the
last
seasonal
year
from
October
1999
to
September
2000
shows
retail
sales
for
carbaryl
at
18.7
million
dollars.
Carbaryl
is
listed
as
number
7
based
on
retail
sales
behind
other
active
ingredients
such
as
chlorpyrifos,
diazinon,
imidacloprid,
hydramethylnon
and
tralomethrin.
Therefore
this
sentence
would
be
more
appropriately
worded
as:
"Carbaryl
is
also
used
for
residential
and
other
non
agricultural
uses,
being
the
seventh
most
commonly
used
insecticide
around
the
home."
Page:
7
Figure
1
EPA
comment:
Figure
2
Aventis'
response:
This
is
labeled
as
Figure
2
when
it
is
Figure
1
3.0
Integrated
Risk
Characterization
Introduction
Page:
8
Paragraph:
1
Line:
last
EPA
comment:
Carbaryl
is
mobile
to
very
mobile
in
the
environment
(Kf
=1.7
to
3.2).
Aventis'
response:
The
upper
value
Kf
for
carbaryl
should
be
listed
as
3.5
as
referenced
by
EPA
elsewhere
(e.
g.
Table
3,
page
20)
in
the
document.
The
classification
of
carbaryl
as
mobile
to
very
mobile
is
inconsistent
with
measured
Koc
values
of
177
to
249.
According
to
the
widely
used
classification
scheme
of
McCall
et
al.
carbaryl
would
be
classified
as
having
medium
mobility
in
soil.
This
classification
of
medium
mobility
is
further
supported
by
the
acceptable
column
leaching
study
(MRID
43320701)
in
which
carbaryl
residues
were
only
slightly
mobile
in
a
number
of
soils.
Aquatic
Organisms
Page:
10,
Paragraph:
1,
Line:
13
EPA
comment:
Submission
of
a
FETOX
amphibian
toxicity
study
is
encouraged.
Aventis'
response:
16
The
data
requirement
should
be
deleted.
From
the
published
results
it
is
evident
that
carbaryl
is
practically
non
toxic
to
the
bullfrog.
Effects
in
plain
leopard
frogs
are
reported
at
levels
well
above
environmental
concentrations.
These
results
were
obtained
testing
U.
S.
native
species.
In
the
proposed
FETOX
assay
a
non
native
species
Xenopus
laevis
is
used.
This
African
species
is
unique
in
its
behavior.
Neither
the
species
nor
the
test
methods
are
suitable
for
ecotoxicological
purposes.
As
the
risk
to
amphibians
can
be
evaluated
from
the
studies
cited,
and
as
the
effects
are
only
at
levels
well
above
the
EEC,
this
study
should
not
be
required.
Page:
10,
Paragraph:
3,
Line:
6/
7
EPA
comment:
…resulting
in
a
temporary
impairment
of
burying
behavior
and
increasing
exposure
to
predators.
Aventis'
response:
A
reference
for
this
statement
should
be
added.
Page:
11,
Paragraph:
2,
Line:
7
EPA
comment:
In
a
mesocosms
study,
at
carbaryl…
Aventis'
response:
Typographical
error.
Change
to
"In
a
mesocosm
study,
at
carbaryl…"
Terrestrial
Organisms
Page:
12
Paragraph:
2
EPA
comment:
(use
of
rock
dove
LD50
)
Aventis'
response:
The
reference
cited
for
this
value
in
Table
1
of
Appendix
D
is
currently
not
available
to
Aventis.
Table
1
of
Appendix
D
gives
a
range
of
1000
–
3000
mg/
kg
for
the
LD50.
It
should
be
assured
that
1000
is
indeed
the
correct
value.
Page:
12
Paragraph:
3
Line:
3
6
EPA
comment:
On
a
chronic
basis,
the
NOAEC
is
300
ppm
for
the
mallard
duck,
based
on
adverse
reproduction
effects,
including
reduced
egg
production,
decreased
fertility,
increase
incidence
of
cracked
eggs,
increased
embryonic
mortality,
and
reduced
hatching
success.
Aventis'
response:
The
sentence
should
be
changed.
The
embryonic
mortality
and
the
hatching
success
were
not
different
from
the
control.
17
Page:
13
Paragraph:
1
Line:
1
EPA
comment:
…(
rat
LD50
=
307
mg/
kg)
Aventis'
response:
Typographical
error,
the
LD50
is
301
mg/
kg.
Page:
13
Paragraph:
1
Line:
2
–
4
EPA
comment:
…based
on
decreased
fetal
body
weights
and
increased
incomplete
ossification
of
multiple
bones
in
the
laboratory
rat
(LOAEC
=
600
ppm,
NOAEC
=
80
ppm),
has
the
potential
for
mammalian
chronic
effects.
Aventis'
response:
A
new
chronic
reproduction
study
in
rats
has
been
submitted
by
Aventis.
This
study
is
more
relevant
for
an
ecological
risk
assessment
than
the
developmental
study
cited.
The
new
study
resulted
in
a
NOAEC
of
75
ppm.
Page:
13
Paragraph:
3
Line:
1
EPA
comment:
Information
available
in
the
open
literature
suggests
potential
reproduction
effects
of
carbaryl
on
mammals.
Aventis'
response:
The
sentence
should
be
changed
or
deleted.
The
literature
cited
in
the
paragraph
show
ambivalent
results.
While
some
references
seem
to
support
that
sentence,
other
references
do
not
substantiate
such
a
claim.
The
potential
for
reproductive
effects
in
mammals
is
evaluated
in
the
recently
submitted
2
generation
study
in
rats.
No
reproductive
effects
were
seen
in
that
guideline
study.
The
NOAEC
of
75
ppm
was
based
on
pup
mortality.
Page:
13
Paragraph:
4
Line:
5
EPA
comment:
According
to
surveys
conducted
by
the
American
Beekeeping
Federation
and
the
Washington
State
Department
of
Agriculture,
carbaryl
is
one
of
the
pesticides
most
frequently
mentioned
as
being
associated
with
bee
kills.
Aventis'
response:
A
reference
should
be
provided
for
this
statement.
18
Page:
14
Paragraph:
4
Line:
1
4
EPA
comment:
The
uses
of
carbaryl
on
crops
(corn,
cotton,
soybeans,
sorghum,
wheat,
barley,
oats,
and
rye),
forests
and
pasture/
rangeland
were
addressed
by
the
US
Fish
and
Wildlife
Service
(USFWS)
in
the
reinitiation
of
consultation
in
September
1989.
The
Service
found
jeopardy
to
a
total
of
86
species
–
6
amphibians,
47
freshwater
fish,
27
freshwater
mussels,
and
5
aquatic
crustaceans.
Aventis'
response:
The
use
of
carbaryl
on
barley,
oats,
rye,
and
cotton
has
been
cancelled.
It
should
be
noted
that
all
Aventis
CropScience
labels
for
the
technical
materials
and
the
end
use
products
containing
carbaryl
were
amended
to
delete
these
uses.
The
Agency
has
already
approved
the
labeling
changes.
Findings
from
the
assessment
made
by
the
USFWS
should
be
reevaluated
considering
the
cancellation
of
the
use
on
barley,
oats,
rye,
and
cotton.
Page:
14
Paragraph:
5
Line:
7
EPA
comment:
The
RPAs
and
RPMs
in
the
1989
B.
O.
may
need
to
be
reassessed…
Aventis'
response:
The
acronyms
used
should
be
explained.
Endocrine
Disruption
Concerns
Page:
15
Paragraph:
3
EPA
comment:
(Report
on
potential
endocrine
effects)
Aventis'
response:
The
paragraph
should
be
deleted.
As
EPA
pointed
out,
the
findings
reported
in
the
literature
were
made
at
concentrations
well
above
the
highest
peak
concentration
modeled.
Therefore
these
findings
are
irrelevant
for
a
risk
assessment
and
at
the
current
stage
of
discussion
about
endocrine
disruption.
If
the
concern
about
the
endocrine
potential
of
carbaryl
persists,
the
issue
should
be
revisited
once
the
Agency's
endocrine
disrupter
screening
and
testing
program,
as
well
as
a
policy
on
how
to
incorporate
positive
findings
into
an
ecological
risk
assessment
have
been
fully
developed.
Page:
15
Paragraph:
4
EPA
comment:
Furthermore,
a
number
of
field
and
laboratory
studies
report
reproduction
effects
with
mammals,
suggesting
that
the
possibility
of
endocrine
disruption
effects
on
wild
mammals
should
be
further
examined.
19
Aventis'
response:
The
statement
should
be
deleted
or
modified.
As
pointed
out
above,
reports
on
reproductive
effects
of
carbaryl
in
the
open
literature
are
at
least
ambivalent.
The
recently
submitted
2
generation
study
in
rats
demonstrated
the
absence
of
reproductive
effects.
If
the
general
statement
about
the
potential
for
endocrine
disruption
of
carbaryl
is
maintained,
references
(or
a
cross
reference
within
the
document)
for
the
above
claim
should
be
provided.
Uncertainties
Page:
15
Paragraph:
Last
Line:
4
EPA
comment:
In
the
absence
of
a
valid
two
generation
rat
reproduction
study,
mammalian
chronic
RQs
were
based
on
a
rat
prenatal
development
study
NOAEC
(MRID#
44732901).
Aventis'
response:
A
new
two
generation
study
in
rats
was
recently
submitted.
20
4.0
Environmental
Fate
Assessment
Exposure
Characterization
Page:
16
Paragraph:
3
Line:
8
EPA
comment:
Environment
(Kf
=1.7
to
3.2).
Aventis'
response:
The
upper
value
Kf
for
carbaryl
should
be
listed
as
3.5
as
referenced
by
EPA
elsewhere
in
the
document
(e.
g.
Table
3,
page
20).
Page:
16
Paragraph:
3
Line:
last
sentence
EPA
comment:
Detailed
discussion
and
reviews
(DERs)
of
the
studies
that
are
included
in
this
assessment
are
attached
in
Appendix
A.
Aventis'
response:
It
is
inappropriate
to
include
the
DERs
in
the
RED.
A
summary
of
study
findings
is
already
included
in
the
EFED
Chapter.
DERs
should
be
made
available
to
the
public
through
the
regular
procedure
under
the
Freedom
of
Information
Act
after
they
have
been
reviewed
and
cleared
for
confidential
business
information.
Page:
16
Paragraph:
4
Line:
4
EPA
comment:
lower
levels
(generally
less
than
0.01
:
/L).
Aventis'
response:
value
missing
units
(generally
less
than
0.01
:
g/
L).
Page:
16
Paragraph:
5
Line:
4
EPA
comment:
…monitoring
data
is
of
limited
utility
in
developing
EECs
for
ecological
and
human
health
risk
assessment.
Aventis'
response:
The
drinking
water
monitoring
program
conducted
by
the
registrant
provides
a
real
world
assessment
of
the
potential
for
human
exposure
to
carbaryl
in
drinking
water
derived
from
surface
water.
Drinking
water
concentrations
derived
from
PRZM/
EXAMS
greatly
overestimate
the
potential
exposure
to
carbaryl
in
drinking
water,
generally
by
several
orders
of
magnitude.
21
Page:
17
Paragraph:
1
Line:
2
3
EPA
comment:
The
maximum
rate
was
taken
from
the
carbaryl
labels.
Aventis'
response:
It
would
be
of
benefit
for
the
Agency
to
be
explicit
and
list
the
carbaryl
labels
that
were
used
to
develop
the
maximum
application
rates
for
the
model
scenarios.
The
reference
cited
in
the
EFED
Chapter
regarding
the
use
of
carbaryl
on
crops
indicate
that
current
labels
were
not
used
for
the
Agency's
assessment.
Many
of
these
crops
have
been
deleted
from
Aventis'
labels
for
a
few
years
Application
rates,
number
of
applications
per
season,
and
PHI's
also
have
changed
for
several
crops
on
the
labels.
Page:
17
Paragraph:
2
Line:
2
EPA
comment:
For
the
Index
Reservoir
scenario
using
maximum
label
rates,
acute
EEC
values
ranged
from
about
10
:
g/
L
from
sugar
beets
to
about
500
:
g/
L
from
citrus
(Table
6).
Aventis'
response:
Table
6
on
page
33
shows
a
concentration
of
19
:
g/
L
for
sugar
beets
treated
with
the
maximum
label
rate
of
2
x
1.5
lb
ai,
not
10
as
stated
in
this
sentence.
A
low
EEC
value
of
9
:
g/
L
for
sugar
beets
results
from
the
"maximum
reported"
application
scenario
of
1
x
1.2
lb
ai/
A.
Page:
17
Paragraph:
2
Line:
3
EPA
comment:
Chronic
EECs
ranged
from
about
1
to
28
:
g/
L.
Aventis'
response:
Table
6
on
page
33
shows
that
this
is
correct
when
considering
all
of
the
model
scenarios.
However,
either
the
same
maximum
label
rate
reference
should
be
used
as
in
the
preceding
sentence
(in
which
case
the
minimum
chronic
EEC
would
be
2),
or
the
basis
for
the
preceding
sentence
should
be
changed
from
the
maximum
label
rate
to
include
all
application
scenarios
to
keep
the
comparisons
consistent.
Page:
17
Paragraph:
2
Line:
8
EPA
comment:
The
results
of
the
modeling
provide
an
(sic)
conservative,
though
not
unreasonable,
estimate
on
(sic)
possible
concentrations
[in]
drinking
water.
Aventis'
response:
It
should
be
clear
that
Aventis'
surface
water
monitoring
program
provides
a
more
reasonable
estimate
of
the
potential
drinking
water
exposure
to
carbaryl
than
the
modeling
numbers,
which
overestimate
exposure
by
several
orders
of
magnitude.
22
Page:
17
Paragraph:
2
Line:
last
EPA
comment:
…and
model
input
and
output
files
are
attached
in
appendix
B.
Aventis'
response:
The
PRZM
input
files
for
only
the
Index
Reservoir
drinking
water
modeling
were
provided
as
an
electronic
copy.
The
PRZM
input
files
for
the
standard
pond
scenarios
were
not
provided
in
the
draft
RED
so
Aventis
could
not
assess
the
data.
None
of
the
output
files
were
provided.
Page:
18
Figure
2
EPA
comment:
Figure
1.
Generalized
carbaryl
degradation
pathway
Aventis'
response:
This
should
be
labeled
Figure
2,
not
Figure
1.
Page:
19
Table
3
EPA
comment:
Hydrolysis
half
life
at
pH
9
stated
to
be
5
hours.
Aventis'
response:
The
study
results,
and
the
summary
of
the
study
presented
on
page
20,
show
the
correct
half
life
at
pH
9
to
be
3.2
hours.
Page:
19
Table
3
EPA
comment:
Aerobic
Aquatic
half
life
4.9.
Aventis'
response:
The
Aerobic
Aquatic
half
life
is
4.9
days
Page:
19
Table
3
EPA
comment:
Soil
metabolism
T1/
2,
anaerobic,
assumed
stable
23
Aventis'
response:
If
this
guideline
is
satisfied
by
the
data
submitted
for
guideline
162
3,
it
is
not
clear
why
the
compound
is
assumed
to
be
stable
rather
than
having
a
half
life
in
line
with
the
72
days
that
resulted
from
the
anaerobic
aquatic
study.
Although
this
parameter
plays
a
fairly
insignificant
role
in
estimating
the
amount
of
carbaryl
available
for
runoff
in
the
models,
it
could
play
a
significant
role
if
one
were
to
use
this
value
in
estimating
leaching
potential
in
subsurface
horizons.
Page:
20
Table
3
EPA
comment:
Batch
Equilibrium
1/
n
values
ranged
from
0.86
1.02
Aventis'
response:
These
values
are
for
the
desorption
isotherms
only.
For
the
adsorption
isotherms
that
were
used
to
calculate
the
adsorption
Kf
and
Koc
values
listed
in
the
table,
the
correct
range
of
1/
n
values
are
0.78
to
0.84
as
stated
on
page
22.
Page:
20
Table
3
EPA
comment:
Foliar
Dissipation
30
days
Willis
and
McDowell,
1987
Aventis'
response:
The
foliar
dissipation
half
life
listed
by
EFED
is
incorrect.
Table
IV
of
the
Willis
and
McDowell
review
lists
10
foliar
half
lives
for
various
formulations
of
carbaryl
applied
to
different
crops.
Five
of
these
half
lives
are
for
a
study
designed
to
evaluate
a
new
analytical
procedure
for
measuring
carbaryl
residues
on
plants.
This
study
was
conducted
on
plants
grown
in
a
greenhouse,
with
some
of
them
receiving
an
unknown
amount
of
simulated
rainfall.
These
studies
on
greenhouse
grown
plants
should
not
be
used
to
evaluate
foliar
persistence
in
the
field.
The
foliar
persistence
of
pesticides
can
be
considerably
different
for
residues
on
and
in
plants
grown
in
greenhouses
versus
the
field.
Eliminating
the
half
lives
for
the
greenhouse
grown
plants
results
in
the
following
half
lives
for
carbaryl
on
field
plants:
Cotton,
1.2,
1.3,
1.5
days;
strawberry,
4.1
days;
tomato
1.4
days.
Therefore,
the
longest
half
life
of
4.1
days
should
be
listed
in
this
table.
Aventis
intends
to
conduct
a
more
thorough
review
of
the
data
on
the
foliar
dissipation
of
carbaryl
and
prepare
a
more
detailed
response
during
the
60
day
public
comment
period.
24
Persistence
Microbially
Mediated
Processes
Page:
21
Paragraph:
3
Line:
3
EPA
comment:
with
an
initial
concentration
of
11.2
mg/
L,
degraded
with
a
half
life
of
4.0
days
in
sandy
Aventis'
response:
The
units
for
ppm
soil
concentration
should
be
given
as
mg/
kg.
Page:
21
Paragraph:
3
Line:
4
5
EPA
comment:
The
major
degradate
was
1
naphthol
which
further
degraded
rapidly
to
non
detectable
levels
within
14
days.
Aventis'
response:
The
data
from
this
study
demonstrate
that
under
aerobic
soil
conditions
the
formation
and
decline
of
1
naphthol,
starting
from
parent
carbaryl
is
complete
in
less
than
14
days.
The
study
data
show
an
average
maximum
1
naphthol
level
of
34.5%
of
applied
carbaryl
by
day
1,
declining
to
2.8%
by
day
2,
0%
by
day
4,
0.2%
by
day
7
and
0%
at
day
14.
These
data
suggest
a
preliminary
half
life
of
less
than
1
day
for
the
major
degradate
1
naphthol.
Page:
21
Paragraph:
3
Line:
8
9
EPA
comment:
In
anaerobic
aquatic
soil
carbaryl
with
an
about
10
mg/
L
degraded
with
a
half
life
of
72.2
days.
Aventis'
response:
Several
words
appear
to
be
missing
from
this
sentence.
One
suggestion:
"Carbaryl
degraded
with
a
half
life
of
72.2
days
in
anaerobic
aquatic
sediment
with
an
initial
carbaryl
concentration
of
about
10
mg/
L."
Page:
22
Paragraph
carried
over
from
page
21
Line:
4
on
pg
22
EPA
comment:
Chudhry
and
Wheeler,
1988
Aventis'
response:
This
reference
is
not
included
in
the
reference
list
25
Mobility
Page:
22
Paragraph:
1
Line:
1
EPA
comment:
Carbaryl
is
considered
to
be
mobile
to
very
mobile
in
soils.
Aventis'
response:
See
response
directly
below.
Page:
22
Paragraph:
3
Line:
1
2
EPA
comment:
Based
on
batch
equilibrium
experiments
(MRID
43259301)
carbaryl
was
determined
to
be
very
mobile
to
mobile
in
soils.
Aventis'
response:
The
classification
of
carbaryl
as
mobile
to
very
mobile
is
inconsistent
with
measured
Koc
values
of
177
to
249.
According
to
the
widely
used
classification
scheme
of
McCall,
et
al.
(1980)
wherein
Koc
values
between
150
and
500
denote
medium
mobility
in
soil,
carbaryl
would
be
classified
as
having
medium
mobility
in
most
soils.
This
classification
of
medium
mobility
is
further
supported
by
the
acceptable
column
leaching
study
(MRID
43320701)
in
which
aged
carbaryl
residues
were
only
slightly
mobile
in
a
number
of
soils.
The
mobility
of
carbaryl
would
be
expected
to
be
higher
in
sandy
soils
or
in
soils
of
low
organic
matter.
Field
Dissipation
Page:
22
Paragraph:
5
Line:
3
EPA
comment:
The
submitted
field
and
aquatic
dissipation
studies
were
determined
to
be
unacceptable,
and
did
not
provide
useful
information
on
movement
and
dissipation
of
carbaryl
or
its
degradation
products.
Aventis'
response:
The
field
dissipation
study
(MRID
41982605)
submitted
in
1991
demonstrated
that
carbaryl
dissipated
very
rapidly
(t1/
2
<
1
week)
with
no
measurable
leaching.
The
study
included
two
sites,
one
in
North
Carolina
and
one
in
California.
At
the
North
Carolina
site,
~
95%
of
the
Time
0
residues
had
dissipated
by
the
first
sampling
period
7
days
after
application
(the
planned
first
sampling
at
3
days
was
not
collected
due
to
rain).
Similarly,
~
85%
of
the
Time
0
residues
had
dissipated
by
7
days
after
application
at
the
California
site.
Concerning
the
movement
of
carbaryl,
samples
were
taken
to
a
depth
of
0.9
meters
in
increments
of
0.15
meters.
No
residues
were
found
below
the
upper
0.15
meters.
26
Page:
23
Paragraph:
3
Line:
2
EPA
comment:
Because
of
inappropriate
sampling
intervals,
poor
sample
storage
stability,
lack
of
degradate
monitoring,
rainfall
and
irrigation
that
were
less
than
evapotranspiration,
and
irrigation
water
with
high
pH,
these
studies
do
not
provide
reliable
information
on
the
rate
of
dissipation
of
parent
carbaryl
or
formation
of
degradation
products.
Aventis'
response:
The
estimated
half
life
determined
from
this
study
was
<
3
days.
Sampling
at
intervals
such
that
several
sampling
events
are
taken
prior
to
the
half
life
of
the
product
is
impractical
for
rapidly
degrading
chemicals
(e.
g.,
those
with
half
lives
less
than
a
week).
For
this
rapidly
degrading
chemical
an
estimate
of
the
half
life
should
be
sufficient
for
risk
assessments
even
if
it
is
not
precise.
After
the
report
was
submitted
to
California,
the
freezer
storage
stability
recoveries
at
six
and
nine
months
were
measured
but
not
reported.
Rainfall
plus
irrigation
approximated
an
inch
a
week
and
was
more
than
enough
to
maintain
a
good
soil
moisture
for
agricultural
purposes.
Sulfuric
acid
is
routinely
added
to
irrigation
water
in
the
region
of
California
where
the
field
test
was
conducted
to
neutralize
the
water's
high
pH.
Although
not
stated
in
the
report,
the
irrigation
water
in
the
California
trial
was
treated
in
the
typical
commercial
fashion.
The
acid
is
injected
into
the
irrigation
pipe
as
water
is
pumped
through
it.
Unfortunately,
the
pH
of
the
water
arriving
at
the
field
after
treatment
was
not
measured.
Aquatic
Field
Dissipation
Page:
24
Paragraph:
2
Line:
3
EPA
comment:
They
(do)
not
provide
useable
information
on
the
dissipation
of
carbaryl
and
1
naphthol
in
aquatic
field
conditions.
Aventis'
response:
The
soil
metabolism
study
referred
to
in
the
report
found
that
the
total
water
soluble
metabolites
did
not
exceed
5%
of
the
total
radioactive
residue,
the
primary
hydrolysis
product,
1
naphthol,
was
not
found,
and
that
the
only
analyte
of
concern
was
the
parent
insecticide,
carbaryl.
A
soil
metabolism
study
reviewed
concurrently
by
the
Agency
was
issued
later
(MRID
42785101,
classified
"acceptable")
with
similar
results.
Although
the
major
soil
metabolite,
1
naphthol,
was
found
at
significant
levels
at
day
0
and
day
1,
the
levels
were
less
than
0.7%
by
day
4
and
non
detectable
by
day
14.
Two
other
metabolites
were
identified
but
never
exceeded
levels
of
1.7%
of
the
total
residue.
Again
the
only
residue
of
concern
was
the
parent
insecticide,
carbaryl.
If
present,
1
naphthol
would
have
been
detected
by
the
residue
method
used
to
measure
the
residues
of
carbaryl
in
the
soil.
27
The
estimated
half
life
determined
from
this
study
was
<
2
days.
Sampling
at
intervals
such
that
several
sampling
events
are
taken
prior
to
the
half
life
of
the
product
is
impractical
for
rapidly
degrading
chemicals
(e.
g.
those
with
half
lives
less
than
a
week).
Page:
24
Paragraph:
2
Line:
4
EPA
comment:
Frozen
storage
stability
data
were
provided
for
only
6
months,
although
the
water
samples
were
stored
for
up
to
14
months
and
the
soil
samples
were
stored
for
up
to
17.5
months
prior
to
analysis.
The
data
suggest
that
carbaryl
and
1
naphthol
degraded
significantly
during
storage.
In
the
six
months
of
storage
carbaryl
degraded
an
average
of
34
%
in
Texas
water
and
39%
in
from
Mississippi.
1
naphthol
degraded
50%
in
water
from
Texas
and
69%
from
Mississippi.
Degradation
did
not
appear
linear,
and
it
is
not
possible
to
extrapolate
out
to
14
months.
It
was
therefore
not
possible
to
evaluate
the
actual
concentrations
of
carbaryl
and
1
naphthol
in
the
samples
or
estimate
the
dissipation
rates.
Aventis'
response:
The
existing
6
month
storage
stability
provides
sufficient
information
to
calculate
the
concentrations
of
carbaryl
in
the
samples.
However,
the
metabolite
1
naphthol
was
shown
to
degrade
significantly
under
the
same
freezer
conditions.
This
instability
simply
confirms
that
1
naphthol's
presence
in
the
environment
would
be
very
limited
and
should
not
be
of
concern.
Foliar
Dissipation
Page:
24
Paragraph:
Last
EPA
comment:
The
reported
rates
of
carbaryl
dissipation
from
foliar
surfaces
varies
from
1
days
to
30
days.
In
their
review
of
literature
data
on
pesticide
foliar
persistence,
Willis
and
McDowell
(1987)
report
that
carbaryl
dissipation
rates
varied
from
1.2
to
29.5
days…
For
terrestrial
risk
assessment
modeling
EFED
used
35
days…
Aventis'
response:
As
stated
in
comments
to
Table
3,
the
foliar
dissipation
half
life
used
by
EFED
for
terrestrial
risk
assessment
is
too
long
and
should
be
corrected.
Table
IV
of
the
Willis
and
McDowell
review
lists
10
foliar
half
lives
for
various
formulations
of
carbaryl
applied
to
different
crops.
Five
of
these
half
lives
are
for
a
study
designed
to
evaluate
a
new
analytical
procedure
for
measuring
carbaryl
residues
on
plants.
This
study
was
conducted
on
plants
grown
in
a
greenhouse,
with
some
of
them
receiving
an
unknown
amount
of
simulated
rainfall.
These
studies
on
greenhouse
grown
plants
should
not
be
used
to
evaluate
foliar
persistence
in
the
field.
The
foliar
persistence
of
pesticides
can
be
considerably
different
for
residues
on
and
in
plants
grown
in
greenhouses
versus
the
field.
Eliminating
the
half
lives
for
the
greenhouse
grown
plants
results
in
the
following
28
half
lives
for
carbaryl
on
field
plants:
Cotton,
1.2,
1.3,
1.5
days;
strawberry,
4.1
days;
tomato
1.4
days.
Therefore,
the
longest
half
life
of
4.1
days
should
be
used
for
terrestrial
risk
assessment
modeling.
Aventis
will
conduct
a
more
thorough
review
of
the
data
on
the
foliar
dissipation
of
carbaryl
and
prepare
a
more
detailed
response
during
the
60
day
public
comment
period.
Atmospheric
Transport
Page:
25
Paragraph:
1
Line:
2
EPA
comment:
Waite,
et
al.,
1995
Aventis'
response:
This
reference
is
not
included
in
the
reference
list
Page:
25
Paragraph:
1
Line:
3
EPA
comment:
Beyer
et
al.,
(1995)
Aventis'
response:
This
reference
is
not
included
in
the
reference
list
Page:
25
Paragraph:
3
Line:
5
EPA
comment:
Schomburg
et
al.
(1991)
Aventis'
response:
This
reference
is
not
included
in
the
reference
list
1
Naphthol
Fate
and
Transport
Page:
26
Paragraph:
2
Line:
1
2
EPA
comment:
In
an
aerobic
soil
metabolism
study
(MRID
42785101),
1
naphthol
degraded
rapidly
to
non
detectable
levels
within
14
days.
29
Aventis'
response:
The
data
from
this
study
demonstrate
that
under
aerobic
soil
conditions
the
formation
and
decline
of
1
naphthol,
starting
from
parent
carbaryl,
is
complete
in
less
than
14
days.
The
study
data
show
an
average
maximum
1
naphthol
level
of
34.5%
of
applied
carbaryl
by
day
1,
declining
to
2.8%
by
day
2,
0%
by
day
4,
0.2%
by
day
7
and
0%
at
day
14.
These
data
suggest
a
preliminary
half
life
of
less
than
1
day
for
the
major
degradate
1
naphthol.
This
half
life
can
be
used
for
preliminary
environmental
fate
modeling
to
estimate
EECs
for
1
naphthol.
Page:
26
Paragraph:
3
Line:
1
EPA
comment:
No
guideline
information
was
submitted
on
1
naphthol
sorption.
Literature
information
suggests
that
it
is
not
strongly
sorbed.
Aventis'
response:
The
statement
suggesting
that
1
naphthol
is
not
strongly
sorbed
to
soil
should
be
deleted.
In
support
of
the
1
naphthol
sorption
statement
the
Agency
has
cited
only
one
paper
by
Karthikeyan
et
al.
(1999)
that
was
conducted
using
aluminum
hydroxide
as
the
sorbent.
Soil
is
composed
of
much
more
than
aluminum
hydroxide,
so
this
study
is
more
of
a
mechanistic
description
of
sorption
to
this
one
component
of
soil
and
not
a
study
of
sorption
to
soil
as
a
whole.
This
cited
study
reported
that
1
naphthol
does
not
show
significant
sorption
to
aluminum
hydroxide
when
allowed
to
sorb
for
20
hours
in
the
dark
in
the
absence
of
oxygen.
However,
there
was
a
significant
increase
in
sorption
with
increasing
equilibration
time,
and
as
the
Agency
stated,
the
increase
is
influenced
by
pH,
as
would
be
expected
for
an
acidic
phenolic
compound.
Additional
information
available
in
the
literature
demonstrates
that
the
sorption
of
1
naphthol
to
soil
is
stronger
than
that
seen
for
carbaryl
itself.
Hassett
et
al.
(1981)
have
demonstrated
that
the
sorption
of
1
naphthol
was
the
result
of
sorption
to
organic
carbon
resulting
in
an
average
Koc
of
431
±
40
for
10
of
the
16
soil
samples
they
tested.
In
the
remaining
6
soil
samples
the
Koc
was
even
higher
(1,645
to
15,618).
Hassett
et
al.
(reference
submitted
as
part
of
30
day
response
document)
hypothesized
that
the
higher
Kocs
in
these
6
soils,
in
which
the
organic
carbon
to
clay
ratio
was
very
low,
the
clay
surfaces
were
more
accessible
and
the
sorption
of
1
naphthol
was
apparently
controlled
by
the
clay
fraction.
In
Burgos
et
al.
(1999),
cited
by
EPA
elsewhere
in
the
RED,
it
was
shown
that
there
is
significant
sorption
of
1
naphthol
to
two
sandy
soils,
and
that
oxidative
coupling
reactions
were
responsible
for
the
strongly
bound
portion.
In
an
earlier
paper
by
Burgos
et
al.
(1996)
it
was
shown
that
both
biologically
mediated
and
soil
catalyzed
oxidative
coupling
lead
to
significant
binding
of
1
naphthol
residues
to
soil.
These
data
indicate
that
1
naphthol
is
less
mobile
and
less
susceptible
to
leaching
than
carbaryl
itself,
and
they
demonstrate
that
at
least
a
portion
of
the
1
naphthol
residue
is
tightly
sorbed
to
soil
constituents.
To
meet
the
requirement
by
the
Agency
for
information
on
the
adsorption
and
desorption
of
1
naphthol,
the
registrant
is
conducting
an
adsorption/
desorption
study
to
meet
the
30
163
1
guideline.
Study
results
should
be
available
for
submission
to
the
Agency
in
the
first
quarter
of
the
calendar
year
2002.
Aquatic
Exposure
Assessment
Surface
Water
Page:
26
Paragraph
4
Line
1
EPA
comment:
Five
crop
scenarios:
apples,
field
corn,
sweet
corn,
oranges
and
sweet
potatoes
scenarios
were
use
in
modeling
for
surface
water
EEC.
Aventis'
response:
The
fifth
crop
modeled
was
sugar
beets
(not
sweet
potatoes).
Page:
27
Table
4
EPA
comment:
Hydrolysis
half
life
at
pH
9
stated
to
be
5
hours.
Aventis'
response:
The
study
results,
and
the
summary
of
the
study
presented
on
page
20,
show
the
correct
half
life
at
pH
9
to
be
3.2
hours.
Page:
27
Table
4
EPA
comment:
(Koc
=
211
for
SCIGROW)
Aventis'
response:
This
is
the
mean
Koc.
According
to
EPA
guidance
the
median
Koc
(209)
should
be
used
for
SCI
GROW,
although
this
difference
would
not
be
expected
to
affect
the
model
results.
Pages:
27
28
Table
5
EPA
comment:
Tier
II
surface
water
estimated
environmental
concentration
(EEC)
values
derived
from
PRZM/
EXAMS
modeling
for
use
in
ecorisk
assessment
(calculated
using
standard
pond.)
Aventis'
response:
The
PRZM
input
tables
were
not
provided
for
the
standard
pond
scenarios,
so
the
assumption
is
made
that
the
same
application
methods
were
used
for
the
standard
pond
as
for
the
Index
Reservoir
scenarios
that
were
provided
as
an
electronic
copy
of
a
draft
of
Appendix
B.
31
It
would
be
of
benefit
for
the
Agency
to
state
which
of
the
carbaryl
labels
were
used
to
develop
the
"maximum"
label
application
rate
scenarios.
It
would
be
useful
to
add
another
column
to
this
table
to
specify
which
method
of
application
was
used
to
generate
the
EECs
rather
than
the
generic
"air/
ground"
in
column
1.
There
are
a
number
of
errors
in
the
input
parameters
(noted
below)
that
would
lead
to
changes
in
the
calculated
EECs
and
therefore
the
risk
quotients
for
these
uses.
If
the
modeling
for
the
"average"
scenarios
were
conducted
using
aerial
applications
for
citrus
and
apples
(as
was
the
case
for
the
Index
Reservoir
scenarios),
then
the
model
results
over
estimate
the
contributions
from
spray
drift.
Few
applications
to
these
crops
are
made
aerially.
Therefore,
the
model
results
over
estimate
the
contributions
from
spray
drift
since
the
"average"
applications
to
these
crops
are
made
using
ground
airblast
equipment
with
a
spray
drift
of
6.3%
in
the
model
versus
aerial
applications
with
a
spray
drift
of
16%.
The
"average"
scenario
for
sweet
corn
in
Ohio
should
be
3
applications
at
1.1
lb.
ai/
A/
application
(as
noted
in
the
memo,
"Average
application
rate
from
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD")
and
not
the
2
applications
at
3.4
lb.
ai/
A/
application
as
listed
in
the
table.
It
should
be
noted
that
the
"average"
scenario
presented
in
this
table,
2
applications
per
year
at
3.4
lb.
ai
per
application,
exceed
the
maximum
rate
allowed
on
the
label.
The
maximum
label
rate
application
scenario
for
apples
that
is
allowed
by
the
Sevin
brand
XLR
PLUS
label
(E.
P.
A.
Reg.
No
264
333),
the
Sevin
brand
80WSP
and
CHIPCO
Sevin
brand
80WSP
labels
(E.
P.
A.
Reg.
No
264
526)
and
the
CHIPCO
Sevin
brand
SL
label
(E.
P.
A.
Reg.
No
264
335)
is
5
applications
at
3
lb.
ai/
A/
application
made
every
14
days.
The
scenario
used
in
the
model
applies
less
than
the
maximum
amount
of
product
allowed
by
the
labels.
In
addition,
if
the
same
application
timing
was
used
in
the
modeling
for
the
standard
pond
scenario
as
was
used
in
the
index
reservoir
scenario
(applications
made
by
air
every
4
days)
this
would
be
a
violation
of
the
Aventis
labels
which
restrict
applications
to
a
minimum
of
every
14
days.
The
"average"
scenario
for
sugar
beets
in
Minnesota
should
be
1
application
at
1.3
lb.
ai/
A/
application
(as
noted
in
the
memo,
"Average
application
rate
from
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD")
and
not
1
application
at
1.5
lb.
ai/
A/
application
as
listed
in
the
table.
The
"Citrus"
scenario
would
be
more
appropriately
labeled
Oranges.
For
the
average
scenario,
the
3.4
lb.
ai/
A/
application
rate
listed
in
Table
5
is
for
oranges
(as
noted
in
the
memo,
"Average
application
rate
from
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD"),
which
is
the
highest
"average"
application
rate
for
any
type
of
citrus.
Therefore,
this
"average"
scenario
for
oranges
are
at
the
high
end
for
all
citrus
and
overestimates
the
PRZM/
EXAMS
derived
EECs
for
use
in
the
other
citrus
crops.
"Average"
application
rates
for
other
citrus
as
listed
in
the
memo
are:
32
Lemons
–
1.3
applications
at
2.7
lb
ai/
A/
appl
Grapefruit
–
1.6
applications
at
1.4
lb
ai/
A/
appl
Citrus,
other
–
1.8
applications
at
1.8
lb
ai/
A/
appl
The
maximum
label
application
rate
for
citrus
is
7.5
lb
ai
per
application,
not
5
lb
ai,
with
a
maximum
of
20
lb
ai
total
allowed
per
year.
In
California
only,
a
single
application
is
allowed
at
the
rate
of
5
to
16
lb
ai
per
season
for
control
of
California
red
scale
and
yellow
scale.
Estimated
Environmental
Concentrations
for
Terrestrial
Ecological
Risk
Assessment
Page:
29
Paragraph:
2
Line:
2
4
EPA
comment:
In
the
absence
of
reliable
foliar
dissipation
data
a
dissipation
half
life
of
35
days
is
used.
Published
literature
shows
that
carbaryl
dissipation
rates
vary,
and
are
among
the
highest
observed
for
any
pesticide
(Willis
and
McDowell,
1987).
Aventis'
response:
As
stated
in
more
detail
above,
some
of
the
foliar
dissipation
half
lives
listed
in
this
reference
are
high
because
they
were
generated
in
the
greenhouse,
not
in
the
field,
and
therefore
they
should
not
be
used.
Eliminating
the
half
lives
for
the
greenhouse
grown
plants
results
in
the
following
half
lives
for
carbaryl
on
field
plants:
Cotton,
1.2,
1.3,
1.5
days;
strawberry,
4.1
days;
tomato
1.4
days.
Therefore,
the
longest
half
life
of
4.1
days
should
be
used
for
terrestrial
risk
assessment
modeling.
Page:
29
Paragraph:
2
Line:
6
EPA
comment:
A
more
thorough
description
of
the
model
calculations
and
ELL
FATE
outputs
are
attached
in
Appendix
B.
Aventis'
response:
No
such
description
or
attachments
were
provided,
so
Aventis
did
not
have
the
opportunity
to
evaluate
the
model.
Page:
29
Paragraph:
2
Line:
last
EPA
comment:
…Tables
4,7,
8
and
9,
Appendix
D.
Aventis'
response:
These
tables
are
in
Appendix
C.
33
5.0
Drinking
Water
Assessment
Water
Resources
Assessment
Page:
29
Paragraph:
3
Line:
3
EPA
comment:
Carbaryl
tends
not
to
partition
to
soil,
aquifer
solids,
or
sediment.
Aventis'
response:
This
sentence
is
misleading
and
should
be
reworded.
Carbaryl
does
partition
onto
these
sorbents,
but
the
sorption
coefficients
are
not
high.
Suggest
rewording
this
such
as:
"Carbaryl
tends
not
to
bind
tightly
to
soil,
aquifer
solids,
or
sediment."
Page:
29
Paragraph:
4
EPA
comment:
Under
certain
conditions
carbaryl
can
be
expected
to
persist
in
the
environment.
Under
low
pH
conditions
the
compound
is
stable
to
hydrolysis.
In
anaerobic
environments
metabolism
is
fairly
slow
(t½
=
72
days).
This
suggests
that
carbaryl
may
leach
to
ground
water
and
persist
in
some
aquifers.
Aventis'
response:
This
last
statement
should
be
removed.
In
contrast
to
this
hypothesis
are
the
data
presented
in
the
NAWQA
and
EPA
databases
that
demonstrate
that
carbaryl
is
not
likely
to
leach
to
ground
water
and
is
not
likely
to
persist
in
aquifers.
The
fact
that
carbaryl
has
been
widely
used
in
agricultural
and
urban
settings
for
more
than
35
years,
and
yet
is
found
at
concentrations
greater
than
0.1
:
g
/L
in
only
0.027%
of
the
agricultural
wells,
urban
wells
and
aquifers
sampled
by
NAWQA
(Kolpin,
2001),
indicates
that
this
statement
has
little
merit.
Furthermore,
the
last
sentence
is
in
direct
contradiction
to
the
statement
made
at
the
beginning
of
the
preceding
paragraph
that
carbaryl
"…
has
limited
potential
to
leach
to
ground
water."
Page:
30
Paragraph:
1
Lines
1
3
EPA
comment:
Surface
water
monitoring
studies
show
that
carbaryl
is
the
second
most
widely
detected
insecticide
after
diazinon.
Carbaryl,
at
typically
low
concentrations,
is
found
in
greater
than
20
%
of
surface
samples
at
concentrations
up
to
7
ppb.
Aventis'
response:
These
summary
statements
are
based
on
the
NAWQA
database,
with
the
exception
of
the
7
ppb
concentration.
The
highest
reported
value
in
the
NAWQA
database
is
5.5
ppb.
The
value
of
7
ppb
does
not
come
from
the
NAWQA
database
but
from
the
report
by
Werner
et
al.
(2000).
In
fact,
a
maximum
carbaryl
concentration
of
8.4
ppb
was
reported
for
surface
water
samples
in
the
California
DPR
surface
water
database
(see
discussion
section).
The
sources
of
the
information
should
not
be
mixed,
or
the
source
of
the
information
should
be
explicitly
stated.
34
Drinking
Water
Exposure
Assessment
Page:
30
Paragraph:
2
Line:
3
4
EPA
comment:
Carbaryl
is
the
second
most
commonly
detected
insecticide
in
surface
water,
and
can
be
expected
to
contaminate
drinking
water
derived
from
surface
water
bodies.
Aventis'
response:
The
surface
water
monitoring
program
conducted
by
Aventis
shows
an
insignificant
impact
of
carbaryl
on
drinking
water.
Page:
30
Paragraph:
2
Line:
7
EPA
comment:
The
maximum
reported
value
was
7.0
:
g
/L.
Aventis'
response:
The
maximum
value
reported
in
the
NAWQA
database
is
5.5
:
g
/L.
The
only
carbaryl
detection
reported
in
the
study
by
Werner
et
al.
(2000)
was
7.0
:
g
/L.
The
maximum
value
reported
in
the
California
DPR
Surface
Water
database
is
8.4
:
g
/L.
Since
all
of
the
statistics
made
in
this
paragraph
refer
to
the
NAWQA
data,
the
reference
to
the
maximum
reported
concentration
should
be
5.5
:
g
/L.
Page:
30
Paragraph:
4
Line:
2
EPA
comment:
Older
studies
using
GC
or
GC/
MS
generally
have
poor
recovery
and
quantitation
limits.
Because
of
this
difficulty
in
analysis
the
actual
concentration
of
carbaryl
in
groundwater
and
surface
waters
may
be
higher
than
reported.
Aventis'
response:
The
basis
for
making
this
generalization
is
not
readily
apparent
and
these
statements
should
be
removed.
Comments
regarding
the
recovery
reported
for
the
GC/
MS
method
used
in
the
NAWQA
survey
are
made
below
in
reference
to
statements
made
on
page
34
paragraph
5,
and
are
elucidated
in
the
discussion
section
at
the
end
of
this
response
document.
The
method
detection
limit
(MDL)
reported
for
the
GC/
MS
method
used
for
the
NAWQA
program
is
0.003
ppb
(Zaugg
et
al.,
1995;
Larson
et
al.
,
1999).
The
limit
of
detection
for
the
HPLC/
MS/
MS
method
used
in
the
carbaryl
surface
water
monitoring
study
being
conducted
by
the
registrant
(LOD,
0.002
ppb;
LOQ
0.030
ppb)
is
similar
to
the
GC/
MS
method
used
for
the
NAWQA
program.
In
addition
to
the
GC/
MS
method
used
in
the
NAWQA
program,
carbaryl
was
also
analyzed
by
HPLC/
photodiode
array
detection
in
a
limited
number
of
samples
with
a
MDL
of
0.008
(Werner
et
al.,
1996).
Therefore,
the
quantification
limits
reported
for
the
GC/
MS
method
used
to
generate
a
majority
of
the
carbaryl
data
in
the
NAWQA
database
is
very
similar
to
the
quantification
limits
for
available
HPLC
methods.
See
the
discussion
section
at
the
end
35
of
this
response
document
for
a
summary
of
the
available
NAWQA
data
obtained
by
the
GC/
MS
and
HPLC/
PDA
methods.
Page:
30
Paragraph:
4
Line:
4
EPA
comment:
More
recent
studies
using
HPLC/
MS
should
provide
better
data
on
the
true
extent
and
magnitude
of
water
contamination
from
the
use
of
carbaryl.
Aventis'
response:
Aventis
believes
that
our
ongoing
targeted
surface
water
monitoring
program
using
HPLC/
MS/
MS
accurately
reflects
the
extent
and
magnitude
of
carbaryl
exposure
in
drinking
water
derived
from
surface
water.
Drinking
Water
Modeling
Page:
31
Paragraph:
carried
over
from
page
30
Line:
8
EPA
comment:
A
partial
list
of
input
parameters
for
the
PRZM/
EXAMS
modeling
are
given
in
Table
4.
Aventis'
response:
The
partial
list
of
input
parameters
in
Table
4
includes
multiple
conservative
assumptions
likely
to
lead
to
significant
over
estimation
of
the
potential
surface
water
concentrations
of
carbaryl.
Page:
31
Paragraph:
2
Line:
1
EPA
comment:
For
the
Index
Reservoir
scenario
using
maximum
label
rates,
acute
EEC
values
ranged
from
about
10
:
g/
L
from
sugar
beets
to
about
500
:
g/
L
from
citrus
(Table
6).
Aventis'
response:
Table
6
on
page
33
shows
a
concentration
of
19
:
g/
L
for
sugar
beets
treated
with
the
maximum
label
rate
of
2
x
1.5
lb
ai,
not
10
as
stated
in
this
sentence.
A
low
EEC
value
of
9
:
g/
L
for
sugar
beets
results
from
the
"maximum
reported"
application
scenario
of
1
x
1.2
lb
ai/
A.
Page:
31
Paragraph:
2
Line:
3
EPA
comment:
Chronic
EECs
ranged
from
about
1
to
28
:
g/
L.
36
Aventis'
response:
Table
6
on
page
33
shows
that
this
is
correct
when
considering
all
of
the
model
scenarios.
However,
either
the
same
maximum
label
rate
reference
should
be
used
as
in
the
preceding
sentence
(in
which
case
the
minimum
chronic
EEC
would
be
2),
or
the
basis
for
the
preceding
sentence
should
be
changed
from
the
maximum
label
rate
to
include
all
application
scenarios
to
keep
the
comparisons
consistent.
Page:
31
Paragraph:
2
Line:
6
EPA
comment:
It
is
highly
unlikely
that
any
but
the
most
extensive
targeted
monitoring
would
capture
the
actual
peak
concentrations.
Aventis'
response:
The
role
of
a
peak
concentration
in
dietary
exposure
assessment
is
undergoing
reexamination
within
EPA.
The
current
policy
of
EPA
appears
to
define
a
certain
percentile
as
an
appropriate
value
for
use
in
screening
assessments,
but
the
exact
percentile
to
be
used
is
being
currently
set
by
EPA
management.
(The
most
recent
documents
from
EPA
cite
the
95
th
or
99
th
percentile.)
For
more
comprehensive
assessments,
a
distribution
of
values
is
preferred.
Page:
31
Paragraph:
2
Line:
7
EPA
comment:
The
results
of
the
modeling
provide
a
conservative,
though
not
unreasonable,
estimate
on
possible
concentrations
drinking
water.(
sic)
Aventis'
response:
The
modeling,
performed
according
to
EPA
procedures,
provides
an
upper
bound
estimate
on
potential
concentrations
in
drinking
water
from
surface
water.
Whether
the
modeling
estimates
are
reasonable
depends
on
the
specific
assumptions.
For
carbaryl,
the
three
year
monitoring
program
(conducted
according
to
EPA
and
ILSI
guidance
available
at
the
time
the
study
was
started)
shows
that
the
model
calculations
are
unreasonable.
These
conservative
assumptions
include
a
3x
factor
on
both
the
aerobic
soil
and
aerobic
aquatic
half
lives,
assuming
the
maximum
drift
rate
for
aerial
applications
throughout
the
county
(in
Florida
citrus
almost
all
applications
are
by
air
blast
with
ground
equipment),
and
the
application
rate
over
a
watershed.
The
conservative
nature
of
the
application
assumption
alone
probably
results
in
an
overprediction
by
at
least
two
orders
of
magnitude.
The
modeling
calculations
assume
an
application
rate
of
17.4
lbs/
acre
of
watershed
annually.
In
Hardee
County,
the
county
with
the
highest
usage
of
carbaryl,
the
average
use
rate
on
a
countywide
basis
is
only
0.31
lb/
acre
(See
Appendix
II).
In
Manatee
County,
the
county
with
the
highest
usage
containing
a
watershed
used
to
supply
drinking
water,
the
average
rate
on
a
countywide
basis
is
0.027
lb/
acre.
37
Page:
31
Paragraph:
2
Line:
8
EPA
comment:
A
more
detailed
assessment
of
the
source
of
water
used
to
provide
drinking
water
and
the
relationship
between
the
areas
where
carbaryl
is
used
and
surface
water
sources
is
required
to
more
accurately
evaluate
possible
human
exposures.
Aventis'
response:
As
mentioned
by
EPA
in
this
document,
ground
water
is
the
source
of
the
majority
of
Florida
drinking
water.
Many
of
the
counties
with
the
highest
use
of
carbaryl
contain
no
watersheds
used
to
provide
drinking
water.
As
discussed
more
fully
in
Appendix
I,
the
watershed
supplying
the
Manatee
County
Water
Treatment
Plant
appears
to
have
the
most
carbaryl
usage
of
drinking
water
watersheds
in
Florida.
Water
Treatment
Effects
Page:
31
Paragraph:
3
Line:
8
EPA
comment:
Since
relatively
(sic)
few
water
treatment
facilities
in
the
U.
S.
use
ozone
the
limited
data
available
do
not
indicate
that
carbaryl
is
likely
to
be
degraded
in
the
majority
of
treatment
plants.
Aventis'
response:
The
monitoring
program
conducted
by
the
registrant
shows
that
removal
occurs
in
some
treatment
plants.
The
effect
of
treatment
seemed
to
be
greater
in
systems
using
carbon
treatment.
Page:
33
Table
6
EPA
comment:
Drinking
Water
EECs
Aventis'
response:
Many
of
the
comments
for
this
table
are
similar
to
those
for
the
EECs
for
ecological
risk
found
in
Table
5.
The
PRZM
model
input
parameters
for
the
Index
Reservoir
scenarios
were
received
as
an
electronic
copy
of
a
draft
of
Appendix
B.
These
input
files
are
very
useful
for
assessing
the
scenarios
that
have
been
modeled.
It
would
be
useful
to
add
another
column
to
Table
6
to
specify
which
method
of
application
was
used
to
generate
the
EECs
(and
thus
the
application
efficiency
and
spray
drift
values).
It
would
be
of
benefit
for
the
Agency
to
state
which
of
the
carbaryl
labels
were
used
to
develop
the
"maximum"
label
application
rate
scenarios.
There
are
a
number
of
errors
in
the
input
parameters
(noted
below)
that
would
lead
to
changes
in
the
calculated
EECs
and
therefore
the
risk
quotients
for
these
uses.
38
The
model
parameters
listed
in
the
electronic
draft
of
Appendix
B
show
that
the
"average"
scenarios
for
citrus
and
apples
were
conducted
using
aerial
applications.
Few
applications
to
these
crops
are
made
aerially.
Therefore,
the
model
results
over
estimate
the
contributions
from
spray
drift
since
the
"average"
applications
to
these
crops
are
made
using
ground
airblast
equipment
with
a
spray
drift
of
6.3%
versus
aerial
applications
with
a
spray
drift
of
16%.
The
"maximum
label
rate"
application
scenario
for
apples
that
is
allowed
by
the
Sevin
brand
XLR
PLUS
label
(E.
P.
A.
Reg.
No
264
333),
the
Sevin
brand
80WSP
and
CHIPCO
Sevin
brand
80WSP
labels
(E.
P.
A.
Reg.
No
264
526)
and
the
CHIPCO
Sevin
brand
SL
label
(E.
P.
A.
Reg.
No
264
335)
is
5
applications
at
3
lb
ai/
A/
application
made
every
14
days.
The
scenario
used
in
the
model
applies
less
than
the
maximum
amount
of
product
allowed
by
the
labels.
In
addition,
application
timing
was
used
in
the
modeling
for
the
index
reservoir
scenario
(applications
made
by
air
every
4
days)
that
would
be
a
violation
of
the
Aventis
labels
which
restrict
applications
to
a
minimum
of
every
14
days.
The
"average"
scenario
for
sweet
corn
in
Ohio
should
be
3
applications
at
1.1
lb
ai/
A/
application
(as
noted
in
the
memo,
"Average
application
rate
from
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD")
and
not
the
2
applications
at
3.4
lb
ai/
A/
application
as
listed
in
the
table.
The
PRZM
input
file
shows
the
correct
inputs
of
3
applications
at
1.1
lb
ai/
A/
application.
The
"average"
scenario
for
sugar
beets
in
Minnesota
should
be
1
application
at
1.3
lb
ai/
A/
application
(as
noted
in
the
memo,
"Average
application
rate
from
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD")
and
not
1
application
at
1.5
lb
ai/
A/
application
as
listed
in
the
table
and
the
PRZM
input
file.
The
"Citrus"
scenario
would
be
more
appropriately
labeled
Oranges.
For
the
average
scenario,
the
3.4
lb
ai/
A/
application
rate
listed
in
Table
5
is
for
oranges
(as
noted
in
the
memo,
"Average
application
rate
from
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD"),
which
is
the
highest
"average"
application
rate
for
any
type
of
citrus.
Therefore,
this
"average"
scenario
for
oranges
is
at
the
high
end
for
all
citrus
and
overestimates
the
EECs
for
use
in
the
other
citrus
crops.
"Average"
application
rates
for
other
citrus
as
listed
in
the
memo
are:
Lemons
–
1.3
applications
at
2.7
lb
ai/
A/
appl
Grapefruit
–
1.6
applications
at
1.4
lb
ai/
A/
appl
Citrus,
other
–
1.8
applications
at
1.8
lb
ai/
A/
appl
Ground
Water
Resources
Page:
34
Paragraph:
carried
over
from
page
33
Line:
3
EPA
comment:
U.
S.
EPA.
Pesticides
in
Groundwater
Database
(Jacoby
et
al.,
1992)
39
Aventis'
response:
This
reference
is
not
provided
in
the
reference
list.
Page:
34
Paragraph:
3
Line:
3
EPA
comment:
Detections
were
from
(sic)
mainly
from
three
use
sites:
wheat
(5.8
%
of
well
samples
from
wheat
land
use),
orchards
and
vineyards
(1.7
%
of
well
samples
from
orchard
and
vineyard
land
use),
and
urban
(1.8%
of
urban
groundwater
samples).
Aventis'
response:
Updated
information
(noted
below)
is
not
summarized
in
the
same
manner
as
in
this
statement,
so
direct
comparisons
cannot
be
made
easily.
However,
the
updated
information
indicates
a
similar
pattern
of
low
concentrations
of
carbaryl
detections
in
a
limited
number
of
ground
water
resources.
Page:
34
Paragraph:
3
Line:
6
EPA
comment:
Limitations
in
analytical
methodology
(described
elsewhere)
apply
to
groundwater
sample
analysis
also
suggesting
that
there
(sic)
actual
maximum
concentrations
and
extent
of
contamination
may
be
significantly
higher.
Aventis'
response:
This
statement
is
misleading
and
should
be
deleted.
The
validation
of
the
most
widely
used
GC/
MS
method
for
the
data
contained
in
NAWQA
show
recoveries
of
86
to
94%
at
spiking
levels
of
0.1
to
1.0
:
g/
L
with
an
MDL
of
0.003
:
g/
L.
The
HPLC
method
validation
reported
recoveries
of
58
to
64%
%
at
spiking
levels
of
0.1
to
1.0
:
g/
L
with
an
MDL
of
0.018
:
g/
L.
Furthermore,
using
the
GC/
MS
method,
a
mean
recovery
of
115%
was
found
for
field
matrix
spikes
of
carbaryl
at
spiking
levels
of
0.1
:
g/
L.
With
the
GC/
MS
method
MDL
of
0.003
:
g/
L
and
a
mean
recovery
of
115%
for
the
field
matrix
spikes,
this
method
cannot
reasonably
be
characterized
as
stated
by
EPA.
Additional
details
of
the
method
validations
and
field
matrix
spikes
are
provided
in
the
`Discussion
Section'
at
the
end
of
this
response.
Page:
34
Paragraph:
3
Line:
last
EPA
comment:
…and
updated
information
is
available
at:
http://
water.
wr.
usgs.
gov/
pnsp/
ja/
est32/.
Aventis'
response:
This
web
page
was
last
updated
in
1998.
A
more
recent
update
by
Kolpin
was
posted
June
11,
2001
at:
http://
water.
wr.
usgs.
gov/
pnsp/
pestgw/
and
is
the
source
of
the
updated
information
included
in
the
`Discussion
Section'
at
the
end
of
this
response.
40
Surface
Water
Resources
Monitoring
Data
Page:
34
Paragraph:
4
Line:
5
6
EPA
comment:
Because
of
limitation
in
the
analytical
methods
used
there
is
some
question
as
to
the
accuracy
of
carbaryl
analysis.
Aventis'
response:
This
generalized
statement
needs
to
be
qualified
or
deleted.
Whereas
the
authors
of
reports
written
as
part
of
the
NAWQA
program
have
been
clear
about
the
potential
limitations
of
the
quantitative
nature
of
the
carbaryl
data
in
the
database,
they
have
also
been
clear
about
the
validity
of
the
qualitative
nature
of
the
data.
The
use
of
the
multiresidue
method
in
the
NAWQA
program
does
have
some
limitations
as
a
result
of
the
large
numbers
of
diverse
pesticides
and
degradation
products
that
they
are
monitoring.
However,
the
QC/
QA
data
generated
as
part
of
the
NAWQA
program
(described
in
the
discussion
section
on
surface
water
at
the
end
of
this
response)
demonstrate
the
validity
of
the
detections
of
carbaryl
in
the
studies.
The
monitoring
study
conducted
by
the
registrant,
and
reported
in
this
section,
does
not
have
the
same
potential
limitations
in
the
analytical
method
since
the
method
is
looking
specifically
for
carbaryl.
Therefore,
the
analytical
method
used
by
the
registrant
does
not
raise
questions
about
the
accuracy
of
the
carbaryl
analysis.
Page:
34
Paragraph:
4
Line:
5
6
EPA
comment:
Poor
analytical
methods
probably
have
resulted
in
lower
detection
rates
and
lower
concentrations
than
actually
present.
Aventis'
response:
This
generalized
statement
should
be
deleted
for
reasons
provided
above
and
in
the
discussion
section.
NAQWA
(sic)
41
Change
to
NAWQA
Page:
34
35
Paragraph:
5
Lines:
5
8
EPA
comment:
Carbaryl
analytical
results
are
fairly
poor,
with
a
typical
mean
percent
recovery
of
24%
(
=
15)
in
laboratory
quality
control
samples,
and
a
method
detection
limit
(MDL)
of
0.003
ug/
L.
This
suggests
that
the
values
reported
do
not
represent
the
maximum
concentrations
that
exist,
and
that
surface
water
contamination
may
be
more
widespread
than
the
data
show.
Aventis'
response:
These
statements
are
misleading
and
should
be
updated
with
further
quality
control
data
supplied
by
NAWQA.
A
discussion
of
the
analytical
method
used
in
the
NAWQA
program
is
presented
in
the
USGS
Open
File
Report
95
181
(see
Zaugg
et
al.
(1995)
in
references).
The
mean
percent
recovery
of
24%
noted
above
can
be
found
in
Table
9
of
this
report
and
is
by
no
means
"typical".
A
mean
recovery
value
of
24%
was
reported
for
reagent
grade
water
fortified
at
a
level
of
0.03
µ
g/
L
with
a
method
detection
limit
said
to
be
0.003
µ
g/
L.
Additional
recoveries
for
fortified
water
samples
(reagent
grade,
ground
and
surface
waters)
ranged
from
10
to
202%
(see
discussion
section).
The
carbaryl
data
in
the
NAWQA
database
are
amended
with
an
"E"
qualifier
to
indicate
the
variability
found
with
this
method,
not
because
the
carbaryl
concentrations
are
underestimated.
Additional
evaluations
of
field
blank,
field
matrix
spike
and
lab
control
spike
samples
as
part
of
the
NAWQA
program
can
be
found
in
a
provisional
report
by
Martin
(1999).
This
report
demonstrates
the
lack
of
detection
of
carbaryl
in
100%
of
the
field
blanks,
and
median
recoveries
of
94.4%
in
306
field
matrix
spikes
and
93.0%
in
1000
lab
control
spikes,
each
at
spiking
levels
of
0.1
µ
g/
L.
These
data
suggest
an
adequate
level
of
detection
of
carbaryl
in
the
method
used
in
the
NAWQA
survey
of
surface
and
ground
water.
See
the
additional
discussion
at
the
end
of
this
document
for
further
information
regarding
recoveries
in
spiked
surface
and
ground
water.
Page:
35
Paragraph:
2
Line:
7
EPA
comment:
…at
about
0.1
percent
of
the
amount
used
in
the
basins
(Larson
et
al.,
1999)
http://
water.
wr.
usgs.
gov/
pnsp/
rep/
wrir984222/
load.
html.
The
estimated
carbaryl
use
on
in
agricultural
applications
is
about
4
million
pounds
suggesting
that
400,000
pounds
are
delivered
to
the
nations
streams
draining
agricultural
areas.
42
Aventis'
response:
This
estimated
use
of
carbaryl
for
agricultural
applications
over
estimates
the
use
of
carbaryl
by
about
1
million
pounds.
BEAD
and
USGS
data
cited
on
pages
6
and
7
are
consistent
with
lower
total
pounds
of
carbaryl
applied.
In
addition,
0.1
percent
of
4
million
pounds
would
be
4,000
pounds,
not
400,000
pounds.
If
the
1987
–
1996
average
of
2.5
million
pounds
carbaryl
is
used
in
the
calculation,
the
total
load
suggested
to
be
delivered
to
streams
draining
agricultural
areas
would
be
2,500
pounds.
Registrant
Monitoring
Study
Page:
35
Paragraph:
4
Line:
11
EPA
comment:
Carbaryl
was
analyzed
by
HPLC/
MS
with
a
limit
of
detection…
Aventis'
response:
The
analytical
method
used
by
the
registrant
in
the
surface
water
monitoring
study
uses
tandem
mass
spectrometry
(MS/
MS)
as
the
detection
method.
This
type
of
detection
involves
quantification
of
"daughter"
ions
from
a
selected
mass
fragment
and
is
more
selective
than
an
MS
method.
Therefore,
to
accurately
reflect
these
differences,
the
method
should
be
labeled
as
HPLC/
MS/
MS.
Page:
36
Paragraph:
3
Line:
9
EPA
comment:
In
several
cases
finished
water
had
higher
concentration
than
raw
water,
and
finished
water
had
detectable
carbaryl
when
the
raw
did
not.
The
highest
concentration
measured
was
in
finished
water
(0.18
ppb).
Raw
water
sampled
at
the
same
time
had
much
lower
concentration
(0.010).
43
Aventis'
response:
This
statement
is
misleading
and
certainly
does
not
consider
the
analytical
uncertainty
for
concentrations
below
the
level
of
quantification
and
near
the
level
of
detection.
There
were
only
two
cases
when
finished
water
was
greater
than
raw
water
when
the
concentrations
in
finished
water
were
greater
than
0.01
ppb
(only
one
third
of
the
quantification
limit).
One
case
was
when
the
raw
water
was
0.009
ppb
and
the
finished
water
was
0.011
ppb.
These
two
analyses
are
essentially
equivalent,
especially
considering
that
they
are
only
about
a
third
of
the
quantification
limit.
The
other
case
was
at
the
Deerfield
community
water
system.
This
drinking
water
facility
uses
a
small
river
without
a
reservoir
as
a
source
for
a
small
Community
Water
System.
Farms
are
located
immediately
upstream
of
the
facility.
The
intake
is
also
not
continuous
(shut
down
over
weekends).
Therefore,
getting
a
matching
sample
is
quite
difficult,
especially
for
a
short
duration
spike
as
a
result
of
spray
drift,
summer
thunderstorm,
or
perhaps
a
spill
that
almost
immediately
enters
the
river
a
runoff
event.
The
rarity
of
this
event
is
demonstrated
by
the
absence
of
residues
of
this
magnitude
the
next
year
(2000).
Samples
collected
through
this
time
of
the
year
in
2001
also
do
not
indicate
a
similar
event.
Although
the
data
from
this
site
cannot
be
used
to
determine
the
peak
concentration,
the
data
provide
a
distribution
of
residues
through
the
three
year
period
which
will
define
up
to
the
99
th
percentile
concentration
of
the
distribution.
The
Deerfield,
Michigan
community
water
system
is
one
of
the
systems
in
which
the
greatest
variability
of
residues
would
be
expected.
Most
of
the
other
community
water
systems
are
located
on
larger
rivers,
lakes,
or
reservoirs.
Because
the
design
of
study
called
for
analysis
of
finished
water
only
when
there
were
residues
in
the
raw
water,
there
was
only
one
finished
sample
analyzed
when
the
raw
water
contained
no
residues.
This
sample
was
collected
at
the
Deerfield
community
water
system
at
the
sampling
interval
after
the
finding
of
0.16
ppb
in
the
Deerfield
system.
The
residue
level
in
this
sample
was
0.004
ppb.
The
difference
between
0.004
ppb
and
non
detect
is
insignificant,
and
if
real
can
probably
be
attributed
to
water
at
much
higher
concentrations
remaining
in
the
system
from
the
previous
week.
Page:
36
Paragraph:
4
Line:
1
EPA
comment:
Non
targeted
monitoring,
such
as
the
NAWQA
program,
has
shown
much
higher
concentrations
occur
indicating
that
this
study,
while
useful,
can
not
be
used
to
describe
the
overall
distributions
that
occur
throughout
the
entire
use
area.
Aventis'
response:
The
targets
of
the
drinking
water
monitoring
conducted
by
the
registrant
and
the
NAWQA
program
are
different.
The
NAWQA
program
characterized
surface
water
concentrations
within
a
study
area
while
the
Aventis
drinking
water
monitoring
measured
residues
in
inlets
and
outlets
of
drinking
water
facilities.
Also
the
drinking
water
monitoring
program
considered
only
use
areas
with
drinking
water
supplies.
However,
44
for
FQPA
dietary
assessments,
the
appropriate
target
is
drinking
water
rather
than
surface
water.
The
main
reason
why
the
drinking
water
monitoring
study
did
not
show
residues
as
high
as
in
the
NAWQA
program
is
the
location
of
the
sampling
points.
Drinking
water
supplies
tend
to
be
located
on
larger
surface
water
bodies
than
NAWQA
sampling
points
(or
in
other
words,
the
intakes
for
community
water
systems
tend
to
be
downstream
of
NAWQA
sampling
points).
This
additional
time
allows
for
additional
degradation
and
dilution
to
occur.
Finding
the
highest
concentration
at
the
Deerfield,
Michigan
system
is
not
surprising
since
this
intake
is
on
one
of
the
smallest
surface
water
bodies
included
in
the
monitoring
study
(see
response
to
Page:
36,
Paragraph:
3,
Line:
9
above
for
a
more
detailed
explanation).
Page:
36
Paragraph:
4
Line:
4
EPA
comment:
This
study
does
not
provide
sufficient
information
to
allow
estimation
of
actual
peak
and
mean
concentrations
that
actually
occur
in
all
use
areas.
Aventis'
response:
Because
most
of
the
samples
did
not
contain
carbaryl
residues,
accurate
estimates
of
the
actual
peak
and
mean
concentrations
can
not
be
obtained.
However,
the
distributions
obtained
from
all
sites
can
be
used
to
define
up
to
the
99
th
percentile
concentration.
The
average
cannot
be
accurately
determined;
however,
the
time
weighted
average
is
only
slightly
above
the
limit
of
detection
(and
certainly
less
than
0.01
ppb)
at
all
20
sites.
The
peak
concentration
in
this
study
was
measured
at
a
community
water
system
on
a
small
river.
The
registrant
agrees
that
the
sampling
schedule
was
not
adequate
to
determine
the
true
peak
in
such
systems.
Most
of
the
other
community
water
systems
are
located
on
larger
rivers,
lakes,
or
reservoirs.
Therefore,
the
peak
values
are
not
likely
to
be
an
order
of
magnitude
greater
than
the
amounts
present
in
the
collected
samples.
The
distributions
obtained
in
this
study
are
suitable
for
use
in
dietary
exposure
assessments.
When
EPA
policy
establishes
what
percentile
concentration
is
an
appropriate
regulatory
endpoint,
then
these
percentiles
can
be
determined
for
each
of
the
community
water
systems
monitoring.
These
percentiles
can
then
be
compared
with
DWLOC
values
in
screening
assessments.
Page:
37
Paragraph:
2
Line:
1
EPA
comment:
Only
limited
information
was
submitted
on
sampling
site
selection…
Aventis'
response:
The
summary
in
Appendix
I
of
this
response
provides
a
description
of
the
sites
considered
for
the
monitoring
study
and
the
rationale
for
the
selection
of
the
twenty
sites.
This
information
demonstrates
that
the
community
water
systems
selected
for
this
study
45
are
representative
of
the
systems
that
are
most
likely
to
contain
the
highest
concentrations
of
carbaryl
residues.
Page:
37
Paragraph:
3
Line:
3
EPA
comment:
This
should
include
an
explanation
of
why
this
study
did
not
observe
concentrations
as
high
as
those
found
in
other,
non
targeted
studies,
and
how
the
results
of
this
study
can
be
related
to
concentrations
that
occur
throughout
the
country.
Aventis'
response:
The
main
reason
why
the
drinking
water
monitoring
study
did
not
show
residues
as
high
as
in
the
NAWQA
program
is
the
location
of
the
sampling
points.
Drinking
water
supplies
tend
to
be
located
on
larger
surface
water
bodies
than
NAWQA
sampling
points
(or
in
other
words,
the
intakes
for
community
water
systems
tend
to
be
downstream
of
NAWQA
sampling
points).
This
additional
time
allows
for
additional
degradation
and
dilution
to
occur.
Finding
the
highest
concentration
at
the
Deerfield,
Michigan
system
is
not
surprising
since
this
intake
is
on
one
of
the
smallest
surface
water
bodies
included
in
the
monitoring
study
(see
response
to
Page:
36,
Paragraph:
3,
Line:
9
above).
Since
the
drinking
water
study
targeted
drinking
water
systems
in
high
use
watersheds,
the
data
from
this
study
are
representative
of
the
drinking
water
systems
most
likely
to
contain
carbaryl.
Sacramento
San
Joaquin
River
Delta
Page:
37
Paragraph:
4
Line:
4
5
EPA
comment:
Carbaryl
was
found
to
be
the
sole
causative
agent
at
one
of
20
sites…
The
toxicity
seemed
to
persist
for
several
days…
Aventis'
response:
The
statement
should
be
revised.
The
reference
cited
(Werner
et
al.,
2000)
lists
carbaryl
as
"the
primary
toxicant"
(not
as
the
"sole
causative
agent"),
even
though
an
unknown
was
also
found
at
the
same
time.
No
information
about
the
"unknown"
is
provided.
Both
conclusions
of
"sole
causative"
and
of
"primary
toxicant"
cannot
be
substantiated
without
further
evidence
about
the
nature
and
concentration
of
the
unknown.
Actually,
for
another
site
the
authors
concluded
about
the
unknown
found
there
"in
3
of
21
samples,
toxicity
observed
could
not
be
entirely
explained
by
the
identified
primary
toxicants."
Additionally,
it
is
at
least
questionable
if
the
analytical
method
employed
would
detect
all
potential
toxicants
beside
the
insecticides
it
was
set
up
for.
The
toxicity
seeming
to
persist
is
not
explained
or
substantiated
in
the
reference.
The
citation
of
such
dubious
results
should
be
removed
from
the
RED.
46
6.0
Hazard
and
Risk
Assessment
for
Aquatic
Organisms
Hazard
assessment
for
Aquatic
organisms
Estuarine/
Marine
Fish
Page:
39
Paragraph:
2
Line:
6
EPA
comment:
…carbaryl
water
concentration
of
1.2
:
g/
ml…
Aventis'
response:
To
be
consistent
with
the
rest
of
the
document
the
units
should
be
presented
in
ppm
("
carbaryl
water
concentration
of
1.2
ppm")
Aquatic
Plants
Page:
40
Paragraph:
2
Line:
6
EPA
comment:
Guideline
122
2
is
not
fulfilled.
Aventis'
response:
The
chapter
should
be
revised.
As
detailed
above
(comments
to
Page
2
of
the
Memorandum),
studies
were
submitted
in
1992.
The
status
for
this
requirement
in
an
October
04,
2000
OPP
Guideline
Status
Report
(Chemical
Review
Management
System)
lists
the
guideline
122
2
status
as
"Acceptable/
Satisfied".
Risk
Assessment
for
Aquatic
Organisms
Page:
40
Paragraph:
4
Line:
3
EPA
comment:
…corresponding
levels
of
concern
(LOCs)
is
presented
in
Appendix
D.
Aventis'
response:
The
risk
quotients
are
currently
listed
in
Appendix
C.
Estuarine/
Marine
Fish
Page:
42
Paragraph:
1
Line:
17/
18
EPA
comment:
Chronic
toxicity
studies
with
an
estuarine/
marine
fish
species
is
required.
47
Aventis'
response:
This
requirement
should
be
waived.
Given
the
relatively
short
half
life
of
carbaryl
in
the
aquatic
environment
and
the
low
acute
risk,
it
is
unlikely
that
estuarine/
marine
fish
species
would
be
exposed
to
a
chronic
risk.
Page:
42
Paragraph:
2
Line:
1
EPA
comment:
There
is
one
carbaryl
use
in
particular
that
presents
a
major
acute
and
chronic
risk
to
estuarine/
marine
fish.
Aventis'
response:
This
sentence
should
be
rephrased.
While
there
might
be
an
acute
risk
from
the
application
to
oyster
beds,
given
that
there
is
only
one
application
every
six
years
according
to
the
reference
cited
by
EPA,
it
is
improbable
that
estuarine/
marine
fish
would
be
exposed
to
a
chronic
risk.
7.0
Hazard
and
Risk
Assessment
for
Terrestrial
Organisms
Hazard
Assessment
for
Terrestrial
Organisms
Mammalian
Page:
46
Paragraph:
4
Line:
1
EPA
comment:
With
a
rat
LD50
of
307
mg/
kg…
Aventis'
response:
Typographical
error,
the
rat
LD50
is
301
mg/
kg.
Risk
Assessment
for
Terrestrial
Organisms
Avian
Risk
Nongranular
Formulations
Page:
47
Paragraph:
4
Line:
5
EPA
comment:
…levels
of
concern
(LOCs)
is
presented
in
Appendix
D.
Aventis'
response:
The
risk
quotients
are
currently
listed
in
Appendix
C.
48
Page:
48
Paragraph:
1
Line:
3
EPA
comment:
…
for
34
of
43
uses
at
maximum
reported
rates,
and
for
37
of
72
uses
at
"average"
rates.
(Appendix
D,
…
Aventis'
response:
The
risk
quotients
are
currently
listed
in
Appendix
C.
Granular
Formulations
Page:
48
Paragraph:
2
Line:
5
EPA
comment:
…for
any
of
the
granular
carbaryl
uses
(Appendix
D,
Table
6).
Aventis'
response:
The
risk
quotients
are
currently
listed
in
Appendix
C.
Mammalian
Risk
Risk
to
Herbivores/
Insectivores:
Nongranular
Formulations
Risk
Quotients
for
Herbivores/
Insectivores
Based
on
Less
than
Maximum
Label
Use
Rates
Page:
48
Paragraph:
3
Line:
3
&
4
EPA
comment:
…
(Appendix
D,
Table
10a)
and
maximum
reported
(Doane
data)
use
rates
data
available
for
43
uses
(Appendix
D,
Table
10b)
Aventis'
response:
The
risk
quotients
are
currently
listed
in
Appendix
C.
Risk
Quotients
for
Herbivores/
Insectivores
Based
on
Maximum
Label
Use
Rates
Page:
48
Paragraph:
6
Line:
1
EPA
comment:
Carbaryl
is
moderately
toxic
to
small
mammals
on
an
acute
oral
basis
(rat
LD50
=
307
mg/
kg)
Aventis'
response:
Typographical
error,
the
rat
LD50
is
301
mg/
kg.
By
using
the
lower
LD50
all
acute
mammalian
risk
quotients
will
change
slightly.
49
Page:
49
Paragraph:
1
Line:
3
EPA
comment:
…corresponding
levels
of
concern
(LOCs)
is
presented
in
Appendix
D.
Aventis'
response:
The
risk
quotients
are
currently
listed
in
Appendix
C.
Risk
to
Granivores:
Nongranular
Uses
Chronic
risk:
Nongranular
Uses
Page:
50
Paragraph:
2
Line:
8
EPA
comment:
…summarized
in
Appendix
D,
Table
9.
Aventis'
response:
The
risk
quotients
are
currently
listed
in
Appendix
C.
Reproduction
Effects
Page:
50
&
51
Paragraph:
4
/
1
EPA
comment:
(Review
of
alleged
reproduction
effects
of
carbaryl).
Aventis'
response:
The
paragraphs
should
be
changed.
The
literature
cited
in
these
paragraphs
show
ambivalent
results.
While
some
references
seem
to
support
the
claim
of
reproductive
effects,
other
references
do
not.
The
potential
for
reproductive
effects
in
mammals
was
evaluated
in
the
recently
submitted
2
generation
study
in
rats.
No
reproductive
effects
were
seen
in
this
guideline
study.
The
NOAEC
of
75
ppm
was
based
on
pup
mortality.
Page:
51
Paragraph:
4
EPA
comment:
Feeding
2
or
20
mg/
kg
of
carbaryl
to
pregnant
rhesus
monkeys
(Macacca
mulatta)
Aventis'
response:
This
paragraph
should
be
deleted.
As
there
are
no
native
monkey
species
in
the
U.
S.,
this
reference
is
irrelevant
for
U.
S.
wildlife
species.
Additionally,
the
reference
cited
is
only
a
brief
abstract
article
consisting
of
one
17
line
paragraph.
Such
information
should
not
be
the
basis
for
use
in
a
RED
risk
assessment.
50
9.0
References
(non
MRID)
Some
of
the
references
cited
in
EPA's
list
are
not
full
scientific
articles,
but
only
abstracts
from
meetings
(e.
g.
DeNorsica,
1973;
Doughtery
et
al.
,
1971,
Chapin
et
al.
1997).
Such
"publications"
should
not
be
used
as
references
considered
in
risk
assessments.
Without
a
sufficient
description
of
methods
and
a
presentation
of
detailed
results
these
studies
cannot
be
evaluated
to
determine
if
the
findings
are
or
are
not
scientifically
plausible.
Similarly,
at
least
three
of
the
references
(Gladenko
et
al.
1970,
Krylova
et
al.
1975,
Smirnov
et
al.
1971)
cited
as
proof
for
reproductive
toxicity
are
in
Russian
in
Cyrillic
writing
making
an
appropriate
and
timely
evaluation
difficult.
Due
to
the
limited
review
time
during
the
30
day
comment
period,
the
registrant
could
not
peruse
all
references.
A
more
detailed
response
will
be
provided
during
the
60
day
comment
period.
Page:
59
EPA
comment:
Carmel,
R.
F.,
Imhoff,
J.
C.,
Hummel,
P.
R.,
Cheplick,
J.
M.
and
Donigan,
A.
S.,
1997.
Aventis'
response:
The
first
name
should
be
Carsel.
Page:
59
EPA
comment:
Nkedi
Kizza
and
Brown
(1988)
Aventis'
response:
The
date
should
be
1998.
Appendix
A:
Environmental
Fate
Study
Reviews
(DERs)
Page:
62
ff
EPA
comment:
(Environmental
fate
DERs
are
included)
Aventis'
response:
The
DERs
should
not
be
included
in
the
RED.
Publication
of
DERs
together
with
the
RED
is
unusual
and
will
put
Aventis
in
a
competitive
disadvantage.
Appendix
B:
Refined
Water
Memo
EPA
comment:
MEMO
TO
BE
INSERTED
WHEN
APPROVED
51
Aventis'
response:
This
memo
was
provided
as
an
electronic
copy
and
needs
to
be
inserted
into
the
document.
It
included
text
that
repeated
several
sections
of
the
EFED
document
and
it
included
PRZM
input
tables
for
the
drinking
water
concentrations
using
the
Index
Reservoir
scenario.
It
would
have
been
of
benefit
to
have
the
same
PRZM
inputs
for
the
"standard
pond"
scenarios
that
were
used
to
estimate
surface
water
concentrations
used
in
the
aquatic
risk
assessments.
Appendix
C:
Ecological
Risk
Assessment
Toxicity
Endpoints
Used
in
the
Risk
Assessment
Page:
129
(e
version)
EPA
comment:
Aventis'
response:
Mammalian
acute
oral
LD50
rat
=
307
mg/
kg
The
correct
LD50
is
301
mg/
kg
Mammalian
chronic
(reproduction)
NOAEC
rat
=
80
ppm
The
result
of
the
recently
submitted
2
generation
rat
study
should
be
used
(75
ppm)
Avian
Acute
and
Chronic
Risk
Page:
130
(e
version)
Paragraph:
1
Line:
1
EPA
comment:
Since
the
avian
LC50
is
greater
than
5,000
ppm
(Appendix
E),
Aventis'
response:
The
toxicity
data
are
currently
listed
in
Appendix
D.
Page:
132
–
135
(e
version)
EPA
comment:
(Acute
Risk
Quotients
in
Tables
4
and
5,
as
well
as
throughout
the
document
were
a
reference
is
made
to
these
quotients)
Aventis'
response:
As
the
acute
risk
quotients
are
calculated
on
the
basis
of
an
LC50
of
>
5000
ppm,
the
quotients
should
be
given
as
"<
(value)",
not
just
the
value.
The
values
should
also
be
changed
accordingly
throughout
the
document
where
a
reference
is
made
to
these
quotients.
52
Risk
from
Exposure
to
Non
granular
Products
Page:
137
–
147
(e
version)
EPA
comment:
(Text
and
tables
7
10)
Aventis'
response:
Text
and
tables
should
be
revised.
A
rat
LD50
of
307
mg/
kg
was
used
to
calculate
the
acute
risk
quotients.
The
correct
value
is
301
mg/
kg.
For
calculation
of
the
chronic
risk
quotient
a
NOAEC
of
80
ppm
was
taken
from
a
developmental
study.
The
NOAEC
of
75
ppm
from
a
more
relevant
2
generation
rat
study
recently
submitted
should
be
used
instead.
Risk
from
Exposure
to
Granular
Products
Page:
147
&
148
(e
version)
EPA
comment:
(Text
and
Table
11)
Aventis'
response:
Text
and
tables
should
be
revised.
A
rat
LD50
of
307
mg/
kg
was
used
to
calculate
the
acute
risk
quotients.
The
correct
value
is
301
mg/
kg.
Aquatic
Plants
Page:
152
(e
version)
EPA
comment:
Based
on
a
single
core
aquatic
plant
toxicity
study
available…
…recommended
that
toxicity
studies
with
Lemna
gibba,
Anabaena
flos
aquae,
Skeletonema
costatum,
and
a
freshwater
diatom
be
submitted.
Aventis'
response:
The
respective
studies
were
submitted
to
the
Agency
in
1992
(see
comments
above
to
Page
2
of
the
Memorandum
for
a
complete
list
and
status).
Appendix
D:
Toxicity
Assessment
Page:
157
(e
version)
EPA
comment:
Table
1
(spelling
of
author
in
MRID
No.
00160000)
53
Aventis'
response:
The
author
of
MRID
No.
00160000
should
be
"Hudson
et
al.
".
Also,
it
is
not
obvious
why
the
same
reference
is
one
time
classified
"core"
and
six
times
"supplemental".
The
agency
should
reconsider
if
the
use
of
a
"supplemental"
study
(i.
e.,
rock
dove)
in
calculating
all
acute
RQ
values
is
justified.
Birds,
Chronic
Toxicity
Page:
158
(e
version)
Paragraph:
3
EPA
comment:
Bird
kills
attributed
to
carbaryl
and
involving
blackbirds,
ducks,
starlings,
grackles
turkey,
and
cardinals
have
been
reported
in
Pennsylvania,
Virginia,
New
Jersey,
North
Carolina
and
Michigan
(#
1002048
001,
#1000802
001,
#1007720
020,
##
1000799
003,
#1004375
004).
Aventis'
response:
The
paragraph
should
be
moved
to
the
acute
bird
section.
Also,
only
individuals
familiar
with
this
information
will
recognize
the
numbers
as
the
incident
numbers
from
the
EIIS
database.
An
appropriate
reference
should
be
inserted
here
and
in
similar
citations.
Page:
158
Paragraph:
1
Line:
2
&
3
EPA
comment:
Exposure
to
carbaryl
at
levels
equal
to
or
greater
than
1000
ppm
in
the
mallard
duck
results
in
adverse
reproduction
effects,
such
as
decrease
in
number
of
eggs
produced
include
cracked
eggs,
fertility,
embryonic
mortality,
and
hatching
success.
Aventis'
response:
The
sentence
should
be
changed.
The
embryonic
mortality
and
the
hatching
success
were
not
different
from
the
control.
Mammals,
Acute
and
Chronic
Page:
158
&
159
(e
version)
EPA
comment:
(rat
LD50
of
307
mg/
kg,
NOAEC
80
ppm)
Aventis'
response:
The
acute
LD50
value
for
rat
should
be
corrected
to
301
mg/
kg,
and
the
chronic
NOEAC
to
75
ppm
from
the
2
generation
rat
study.
54
Freshwater
Fish,
Acute
Page:
161
(e
version)
EPA
comment:
Table
6
Aventis'
response:
The
study
classification
of
reference
MRID
40098001
(Mayer
&
Ellersieck,
1986)
should
be
reconsidered
(and
handled
in
a
consistent
fashion).
A
number
of
times
the
reference
is
classified
"core",
while
in
other
instances
the
classification
is
"supplemental".
The
reference
is
an
overview
article
with
little
description
of
test
methods,
analytical
procedures,
GLP,
or
study
details.
The
results
are
generally
listed
in
extensive
tables
(although
summarized
in
the
text
for
some
chemicals).
Such
a
review
article
cannot
be
regarded
as
a
"core"
study
equivalent
to
the
guideline
studies
that
have
to
be
prepared
by
registrants.
Also,
such
studies
with
insufficient
test
method
descriptions
should
not
be
used
in
a
risk
assessment
as
the
primary
source
of
information.
A
submission
based
on
such
data
would
have
certainly
been
rejected
by
the
Agency
Freshwater
Invertebrates,
Acute
Page:
163
(e
version)
EPA
comment:
Table
9
Aventis'
response:
The
study
classification
of
reference
MRID
40098001
(Mayer
&
Ellersieck,
1986)
should
be
reconsidered
(and
handled
in
a
consistent
fashion).
A
number
of
times
the
reference
is
classified
"core",
while
in
other
instances
the
classification
is
"supplemental".
The
reference
is
a
review
article
with
little
description
of
test
methods,
analytical
procedures,
GLP,
or
study
details.
The
results
are
generally
listed
in
extensive
tables
(although
summarized
in
the
text
for
some
chemicals).
Such
an
overview
article
cannot
be
regarded
as
a
"core"
study
equivalent
to
the
guideline
studies
that
have
to
be
prepared
by
registrants.
Also,
such
studies
with
insufficient
test
method
descriptions
should
not
be
used
in
a
risk
assessment
as
the
primary
source
of
information.
Estuarine
and
Marine
Invertebrates,
Acute
Page:
165
(e
version)
EPA
comment:
Table
13,
reference
for
glass
shrimp:
Mayer
&
Ellerersieck
Aventis'
response:
The
reference
should
be
corrected
in
Mayer
&
Ellersieck.
55
Page:
167
(e
version)
Table
15
EPA
comment:
Table
15,
reference
for
MRID
No.
00265665
Aventis'
response:
The
reference
for
MRID
No.
00265665
should
also
contain
the
citation
of
an
author.
56
DISCUSSION
1.
Surface
Water
Concentrations
Summary
of
Registrant
Surface
Water/
Drinking
Water
Monitoring
Program
In
section
V,
page
31
EPA
states
that
the
modeling
simulations
provide
a
conservative,
though
not
unreasonable,
estimate
on
possible
concentrations
in
drinking
water.
The
data
from
the
registrant
drinking
water
monitoring
program
provide
the
best
estimate
of
concentrations
of
carbaryl
in
drinking
water.
This
study
uses
the
sampling
design
for
acute
endpoints
recommended
in
industry/
EPA
meetings
during
1999
(weekly
sampling
during
times
of
peak
concentrations
over
a
three
year
period).
Twenty
sites
representing
the
highest
carbaryl
use
areas
were
selected
based
on
the
information
provided
in
Appendix
I.
These
included
16
sites
in
agricultural
areas
and
4
locations
in
urban
areas.
Samples
were
collected
from
the
inlet
and
outlet
water
at
each
sampling
interval.
Outlet
samples
were
only
analyzed
when
residues
were
present
in
the
inlet
samples.
The
analytical
method
had
a
limit
of
quantification
of
0.030
ppb
and
a
limit
of
detection
of
0.002
ppb.
Table
1
summarizes
the
results
of
the
monitoring
at
each
of
the
20
community
water
systems.
The
maximum
concentration
observed
was
0.16
ppb
(average
of
four
samples,
the
highest
was
0.18
ppb)
in
a
finished
water
sample
from
the
Deerfield
community
water
system
located
on
the
River
Raisin
in
Lenawee
County,
Michigan.
There
were
only
five
other
samples
above
the
limit
of
quantification
of
0.030
ppb.
One
was
a
raw
water
sample
containing
0.31
ppb
from
the
Little
Potato
Slough
Mutual
community
water
system
near
Lodi
in
San
Joaquin
County,
California
(the
source
is
the
Little
Potato
Slough).
The
corresponding
finished
water
sample
was
0.007
ppb.
A
second
one
was
a
raw
water
sample
in
Brockton,
MA
which
contained
0.031
ppb.
No
detectable
residues
were
found
in
the
corresponding
finish
water
sample.
The
last
three
samples
were
from
the
Shades
Mountain
plant
of
the
Birmingham
community
water
system
on
the
Cahaba
River
in
Jefferson
County,
Alabama
.
Two
were
raw
and
finished
samples
of
0.038
and
0.032
ppb
at
the
same
sampling
interval
in
2001.
.
The
other
sample
was
0.035
ppb
in
the
raw
water
in
a
2000
sample
(the
corresponding
finished
sample
did
not
contain
carbaryl
residues.
e.
All
residues
were
transient
so
the
time
weighted
average
concentration
of
carbaryl
in
each
of
the
years
was
0.005
ppb
or
less
at
all
20
community
water
systems.
57
Table
1.
Summary
of
Results
from
the
Carbaryl
Drinking
Water
Monitoring
Study.
Site
Major
Uses
Maximum
Concentration
(ppt)
TWA
Conc.
(ppt)*
in
Outlet
Water
Inlet
Water
Outlet
Water
1999
2000
2001*
*
1999
2000
2001**
1999
2000
Manatee,
FL
citrus
9
3
ND
11
ND
NA
1
1
West
Sacramento,
CA
orchards,
nuts
3
24ND310NA1
1
Lodi,
CA
orchards,
nuts
12
31
ND
4
7
NA
1
1
Riverside,
CA
grapes,
tree
crops
8ND
ND
ND
NANA
1
1
Lake
Elsinore,
CA
citrus
ND
3
6
NA
NA
Analysis
Pending
1
1
Corona,
CA
citrus
ND
ND
ND
NA
NA
NA
1
1
Beaumont,
TX
various
agricultural
ND
ND
ND
NA
NA
NA
1
1
Point
Comfort,
TX
rice,
tree
crops
18
5ND
ND
NDNA
1
1
Penn
Yan,
NY
grapes,
apples
ND
23
ND
NA
ND
NA
1
1
Westfield,
NY
grapes,
apples
21
5
ND
ND
9
NA
1
1
Jefferson,
OR
vegetables,
strawberries
ND
10
ND
NA
ND
NA
1
1
Coweta,
OK
pecans
4
ND
***
ND
NA
***
1
1
Pasco,
WA
apples,
potatoes
2
3
ND
ND
ND
NA
1
1
Manson,
WA
apples
ND
ND
ND
NA
NA
NA
1
1
Deerfield,
MI
vegetables
10
4
ND
160
ND
NA
5
1
Brockton,
MA
cranberries
31
27
ND
ND
3
NA
1
1
East
Point,
GA
home
and
garden
18
18
4
3
8
ND
1
1
Midlothian,
TX
home
and
garden
14
ND
14
ND
NA
ND
1
1
Cary,
NC
home
and
garden
4ND
ND
ND
NANA
1
1
Birmingham,
AL
home
and
garden
23
35
38
ND
ND
32
1
1
*
Annual
Time
Weighted
Concentration,
outlet
values
substituted
for
inlet
values
when
available;
values
below
the
detection
limit
were
considered
to
be
half
the
detection
limit.
**
Results
represent
one
to
six
months
of
sampling
into
the
third
year
program.
***
No
results
available
for
the
third
year
of
sampling.
58
ND
Not
detected.
NA
No
outlet
samples
analyzed
due
to
carbaryl
residues
not
being
detected
in
inlet
samples.
Summary
of
Surface
Water
Data
from
the
NAWQA
Program
In
Section
1
page
3,
Section
4
page
28
and
in
Section
5
page
34,
EPA
has
summarized
the
available
surface
water
monitoring
data
from
the
NAWQA
program
as
having
detections
in
46%
of
the
36
NAWQA
study
units
between
1991
and
1998
with
a
maximum
concentration
of
5.5
ppb.
The
following
tables
summarize
the
carbaryl
analyses
presently
available
from
this
database.
Table
2
is
a
summary
of
the
carbaryl
detections
in
the
updated
database
analysis
recently
reported
by
Larson
(2001).
This
analysis
was
conducted
only
for
samples
collected
during
a
one
year
period
of
the
most
intensive
sampling
from
each
of
the
sampling
sites.
Numerous
samples
were
excluded
from
this
analysis
as
described
by
Larson:
"A
few
sites
with
sufficient
sampling
for
pesticides
were
excluded
from
the
analysis,
in
order
to
minimize
bias
caused
by
over
representation
of
a
particular
land
use
or
agricultural
setting.
…
The
sampling
requirements
for
a
site
to
be
included
in
the
analysis
were
a
minimum
of
8
samples
collected
in
6
or
more
months
during
the
1
year
period.
In
addition,
samples
must
have
been
collected
during
the
expected
period
of
elevated
pesticide
concentrations.
At
most
of
the
sites
used
in
this
analysis,
20
to
30
samples
were
collected
during
the
selected
1
year
period.…
Not
all
samples
collected
during
the
year
at
each
site
were
used
in
the
calculation
of
the
summary
statistics,
however.
Samples
collected
as
part
of
a
fixed
frequency
sampling
schedule
were
included,
along
with
a
much
smaller
number
of
samples
collected
during
selected
high
or
low
flow
conditions.
Samples
collected
over
a
storm
hydrograph,
or
as
part
of
a
study
of
diurnal
variability,
were
excluded
in
order
to
avoid
bias
resulting
from
repeated
sampling
during
extreme
conditions.
"
Table
2.
Carbaryl
Detections
Reported
in
Pesticides
in
Streams
Update
(Larson,
2001)
Site
Type
Number
of
Sites
Number
of
Samples
Carbaryl
Detection
Frequency
(%)
Maximum
Estimated
Concentration
(
µ
g/
L)
All
>=
0.01
(
µ
g/
L)
>=
0.05
(
µ
g/
L)
>=
0.10
(
µ
g/
L)
Agricultural
Streams
62
1560
9.2
5.
7
1.8
0.
9
5.2
Urban
Streams
22
611
43
37
19
12
3.2
Integrator
A
31
595
15
11
2.7
1.
2
0.43
A
Large
streams
and
rivers
59
Results
in
Table
3
and
Table
4
show
a
breakdown
of
all
the
carbaryl
analyses
reported
in
the
USGS
NAWQA
database,
which
was
downloaded
from
their
web
site
July
16,
2001.
The
data
are
reported
separately
for
the
GC/
MS
and
HPLC/
PDA
analyses.
Table
3.
Frequency
of
Carbaryl
Detections
by
GC/
MS
in
Different
Concentration
Ranges
Reported
in
the
NAWQA
Database
as
of
July
16,
2001
Land
Use
Type
Number
of
Samples
<=
MDL
C
>0.003
to
0.01
>0.01
to
0.1
ppb
>0.1
to
1
ppb
>1
ppb
No.
%
No.
%
No.
%
No.
%
No.
%
All
Samples
10379
8388
80.82
617
5.94
1065
10.26
283
2.73
26
0.25
Agricultural
4349
3888
89.40
188
4.32
225
5.17
46
1.06
2
0.
05
Urban
1763
921
52.24
161
9.13
463
26.26
195
11.06
23
1.30
Mixed
A
3648
3022
82.84
247
6.77
345
9.46
33
0.90
1
0.
03
Other
B
619
557
89.98
21
3.39
32
5.17
9
1.
45
0
0
A
Large
streams
and
rivers.
Includes
all
of
the
"Integrator"
sites
listed
in
Larson,
et
al.
.,
1999
and
many
more.
B
Includes
forest,
rangeland,
mining,
etc.
C
The
method
detection
limit
(MDL)
for
carbaryl
analyzed
by
the
GC/
MS
method
is
0.003
µ
g/
L,
but
updated
MDLs
presented
in
the
database
may
be
higher
for
some
analyses
and
are
included
in
this
category.
Table
4.
Frequency
of
Carbaryl
Detections
by
LC/
PDA
in
Different
Concentration
Ranges
Reported
in
the
NAWQA
Database
as
of
July
16,
2001
Land
Use
Type
Number
of
Samples
<=
MDL
C
>0.008
to
0.01
>0.01
to
0.1
ppb
>0.1
to
1
ppb
>1
ppb
No.
%
No.
%
No.
%
No.
%
No.
%
All
Types
5516
5348
96.9
5
9
0.
16
93
1.
69
54
0.
98
12
0.
22
Agricultural
2528
2509
99.2
5
1
0.
04
13
0.
51
3
0.12
2
0.
08
Urban
1189
1064
89.4
9
4
0.
34
64
5.
38
47
3.
95
10
0.
84
Mixed
A
1523
1501
98.5
6
4
0.
26
15
0.
98
3
0.2
0
0
Other
B
276
274
99.2
8
0
0
1
0.
3610.
360
0
A
Large
streams
and
rivers.
Includes
all
of
the
"Integrator"
sites
listed
in
Larson,
et
al.
.,
1999
and
many
more.
B
Includes
forest,
rangeland,
mining,
etc.
C
The
method
detection
limit
(MDL)
for
carbaryl
analyzed
by
the
LC/
PDA
method
is
0.008
µ
g/
L,
but
updated
MDLs
presented
in
the
database
may
be
higher
for
some
analyses
and
are
included
in
this
category.
60
Summary
of
Carbaryl
Analytical
Methods
used
in
the
NAWQA
Program
In
a
number
of
instances
throughout
their
review,
EPA
has
made
reference
to
the
"poor
recovery"
for
carbaryl
noted
in
a
NAWQA
summary
document
(Larson,
1999).
In
this
document,
reference
is
made
to
mean
percent
recovery
of
24%
for
carbaryl
with
a
method
detection
limit
(MDL)
of
0.003
ppb.
The
Agency
cites
this
low
mean
recovery
several
times
as
evidence
that
the
concentrations
of
carbaryl
reported
in
the
database
widely
underestimate
the
actual
concentrations
of
carbaryl
in
the
water
samples.
This
claim
is
misleading
and
should
be
removed
from
each
location
in
the
draft
RED
for
reasons
discussed
below.
Two
analytical
methods
were
developed
as
part
of
the
NAWQA
program
and
both
of
them
have
been
used
in
the
analysis
of
carbaryl.
The
first
method,
used
for
a
majority
of
the
NAWQA
data
reported
for
carbaryl,
is
a
GC/
MS
method
with
an
MDL
of
0.003
ppb
(Zaugg,
et
al.,
1995).
The
second
method,
used
for
a
limited
number
of
samples
in
which
carbaryl
was
analyzed,
is
an
LC/
Photodiode
Array
(PDA)
method
with
an
MDL
of
0.008
ppb
(Werner
et
al.
.,
1996).
In
the
NAWQA
database
the
quantitative
data
for
carbaryl
determined
by
the
GC/
MS
method
are
flagged
with
an
"E",
as
are
data
for
several
other
analytes,
indicating
that
the
analysts
have
noted
"the
potential
for
variable
performance"
in
the
analysis
of
carbaryl.
None
of
the
carbaryl
data
in
the
NAWQA
database
has
been
corrected
for
procedural
recoveries
that
were
noted
in
the
documents
described
above.
Both
of
these
methods
are
discussed
below
in
relation
to
the
recoveries
found
for
the
methods
and
the
potential
impact
this
could
have
on
the
analytical
data
for
carbaryl.
Gas
Chromatography/
Mass
Spectroscopy
Method
The
analytical
method
most
used
in
the
NAWQA
program
for
the
analysis
of
carbaryl
in
water
samples
is
the
GC/
MS
method
described
by
Zaugg,
et
al.,
1995.
In
this
multi
residue
method,
the
analytes
are
first
removed
from
the
water
sample
by
sorption
on
a
C
18
solid
phase
and
are
subsequently
eluted
from
the
solid
phase,
separated
by
GC
and
quantified
by
mass
spectroscopy
with
selected
ion
monitoring.
The
identity
of
each
analyte
is
confirmed
by
the
appropriate
combination
of
retention
time
and
the
ratios
of
three
mass
ions
that
are
characteristic
for
the
analyte.
The
recoveries
for
carbaryl
spiked
at
different
levels
into
three
different
types
of
water
and
analyzed
by
the
GC/
MS
method
are
shown
in
Table
5
Mean
percent
recoveries
of
151
and
202%
were
found
for
carbaryl
fortified
at
0.1
and
1.0
µ
g/
L
in
reagent
grade
water.
A
preliminary
MDL
of
0.046
µ
g/
L
was
calculated
for
the
0.1
µ
g/
L
spiking
level.
Mean
percent
recoveries
of
10
and
75%
were
found
for
carbaryl
fortified
at
0.1
and
1.0
µ
g/
L
in
a
surface
water
sample
collected
from
the
South
Platte
River.
However,
carbaryl
was
detected
at
0.18
µ
g/
L
in
this
water,
or
nearly
twice
the
low
spike
level,
raising
questions
about
the
validity
of
this
result.
Mean
percent
recoveries
of
94
and
86%
were
found
for
carbaryl
fortified
at
0.1
and
1.0
µ
g/
L
in
a
ground
water
sample
collected
from
a
well
in
Denver.
A
mean
recovery
value
of
24%
was
reported
for
reagent
grade
water
fortified
at
a
level
of
0.03
µ
g/
L
with
a
method
detection
limit
calculated
at
0.003
µ
g/
L.
61
Table
5.
Recovery
and
Precision
for
Multiple
Determinations
of
Carbaryl
in
GC/
MS
Method
for
Carbaryl
Spiked
in
Different
Water
Samples
Water
type
Spike
Concentration
(
µ
g/
L)
Mean
Recovery
(%)
MDL
Calculated
Reagent
Grade
0.
1
151
0.046
Reagent
Grade
1.
0
202
Surface
A
0.1
10
Surface
A
1.0
75
Ground
B
0.1
94
Ground
B
1.0
86
Reagent
Grade
0.
03
24
0.
003
A
Surface
water
was
collected
from
the
South
Platte
River
near
Henderson,
Colorado.
This
water
was
found
to
contain
significant
concentrations
of
several
pesticides
including
0.18
µ
g/
L
carbaryl.
This
concentration
was
subtracted
from
the
values
determined
to
give
corrected
results.
B
Ground
water
was
collected
from
the
Denver
Federal
Center
Well
15.
Whereas
the
values
reported
by
Zaugg,
et
al.
(1995)
are
of
interest
in
validating
the
analytical
method,
they
are
not
as
useful
in
evaluating
the
validity
of
the
data
contained
in
the
NAWQA
database.
Therefore,
quoting
the
mean
recovery
value
of
24%
for
reagent
grade
water
spiked
with
carbaryl
at
0.03
µ
g/
L
as
evidence
that
the
concentrations
reported
in
the
database
underestimate
the
actual
concentrations
of
carbaryl
present
in
the
water
samples
is
misleading.
A
more
useful
measure
of
the
validity
of
the
values
in
the
database
lies
with
the
quality
control
checks
that
have
been
incorporated
into
the
analysis
of
samples
in
the
NAWQA
program.
In
a
preliminary
report,
Martin
(1999)
reported
the
quality
control
data
collected
as
part
of
the
NAWQA
surface
and
ground
water
programs
by
the
1991
NAWQA
Study
Unit
teams
or
the
National
Water
Quality
Laboratory
(NWQL)
during
1992
to
1996.
The
data
that
were
compiled
includes
field
blanks,
laboratory
control
spikes
and
field
matrix
spikes,
which
are
defined
below
by
Martin.
"Field
blanks
were
collected
at
the
field
site
with
pesticide
grade
blank
water
and
are
exposed
to
the
field
and
laboratory
environments
and
equipment
similarly
to
environmental
samples.
Field
blanks
measure
the
frequency
and
magnitude
of
contamination
(one
type
of
positive
bias)
in
environmental
water
samples
from
sources
in
the
field
and/
or
laboratory.
Contamination
is
the
main
cause
of
falsepositive
detections
(detecting
a
pesticide
in
a
sample
when,
in
truth,
it
is
absent)."
"Laboratory
control
spikes
measure
the
bias
and
variability
of
the
analytical
method
at
a
particular
concentration.
One
laboratory
control
spike
is
measured
in
each
analytical
set
of
environmental
samples.
The
laboratory
control
spike
has
62
the
target
pesticides
spiked
into
pesticide
grade
blank
water
at
the
laboratory
and
extracted,
processed,
and
analyzed
like
environmental
samples.
Laboratory
control
spikes
analyzed
by
GCMS
were
spiked
at
0.1
:
g/
L…"
"Field
matrix
spikes
measure
the
bias
and
variability
of
the
analytical
method
PLUS
any
potential
effects
caused
by
(1)
degradation
of
pesticides
during
shipment
to
the
laboratory,
(2)
inferences
in
the
determination
of
pesticides
from
unusual
characteristics
of
the
environmental
water
sample
("
matrix
effects"),
and
(3)
other
chemical
processes
that
cause
bias
or
variability
in
the
measurements
of
pesticides
in
environmental
water
samples.
Field
matrix
spikes
analyzed
by
GCMS
were
spiked
at
0.1
:
g/
L,…"
All
of
the
carbaryl
analyses
in
the
field
blanks,
field
matrix
spikes
and
lab
control
spikes
were
conducted
following
the
same
method
described
by
Zaugg
et
al.,
1995
that
was
used
to
generate
a
majority
of
the
carbaryl
data
contained
in
the
NAWQA
database.
The
data
below
were
excerpted
from
Tables
1
to
4
of
the
Martin
report.
Carbaryl
is
found
in
these
tables
under
parameter
82680.
Out
of
145
samples
taken
as
ground
water
field
blanks,
carbaryl
was
not
detected
in
any
of
the
samples
indicating
a
lack
of
false
positives.
Out
of
171
samples
taken
as
surface
water
field
blanks,
carbaryl
was
reported
in
two
samples
(1.2%
false
positives)
at
reported
concentrations
of
0.009
and
0.012
µ
g/
L.
A
summary
of
the
results
for
the
field
matrix
spikes
and
the
lab
control
spikes
is
presented
in
Table
6
Mean
recovery
for
the
306
field
matrix
spikes
was
115%
of
the
spiking
level
of
0.1
µ
g/
L
with
a
median
recovery
of
94.4%
and
a
90
th
percentile
recovery
of
200%.
This
indicates
the
potential
for
the
method
to
over
estimate
the
concentration
of
carbaryl
present
in
the
water
samples
and
is
consistent
with
the
initial
data
reported
for
the
reagent
water
samples
by
Zaugg
et
al.
(1995).
Mean
recovery
for
the
1000
lab
control
spikes
was
99.6%
of
the
spiking
level
of
0.1
µ
g/
L
with
a
median
recovery
of
93%
and
a
90
th
percentile
recovery
of
185%.
These
data
suggest
an
adequate
level
of
detection
of
carbaryl
in
QC
samples
that
were
analyzed
as
part
of
the
same
process
used
in
the
NAWQA
survey
of
pesticides
in
surface
and
ground
water.
63
Table
6.
Percent
Recoveries
of
Carbaryl
Detected
by
the
NAWQA
GC/
MS
Method
in
Laboratory
Control
Spikes
and
Field
Matrix
Spikes
at
a
Spiking
level
of
0.1
µ
g/
L
Sample
Type
Number
of
Samples
10
th
Percentile
Recovery
(%)
Median
Recovery
(%)
Mean
Recovery
(%)
90
th
Percentile
Recovery
(%)
Maximum
Recovery
(%)
Field
Matrix
Spike
306
40
94.4
115.0
199.9
456
Laboratory
Control
Spike
1000
20
93.0
99.6
185.1
329
The
following
disclaimer
was
taken
verbatim
from
the
provisional
report
by
Martin
(1999)
and
pertains
to
the
data
provided
above
on
the
recovery
of
carbaryl
in
the
field
matrix
spike
samples.
"The
field
matrix
spike
data
have
not
been
reviewed
thoroughly,
are
provisional,
and
are
subject
to
change.
Further
review
of
the
field
spike
data
is
expected
to
identify
spikes
that
have
extremely
high
or
low
recoveries
because
the
spikes
either
were
improperly
collected
or
incorrectly
documented
in
the
NAWQA
QC
data
base.
The
expected
result
of
further
review
is
a
data
set
of
field
matrix
spikes
with
fewer
extreme
values
than
the
provisional
data
set
described
in
this
paper;
consequently,
the
provisional
data
set
provides
a
conservative
estimate
of
the
quality
of
the
NAWQA
pesticide
data.
Interpretations
of
field
matrix
spike
data
in
this
paper
are
not
expected
to
change
greatly
as
a
result
of
further
review
of
the
data,
however,
the
statistics
and
confidence
limits
reported
in
the
text
and
tables
will
change
on
further
review
(especially
for
pesticides
with
low
numbers
of
field
spikes
[less
than
50])."
64
High
Performance
Liquid
Chromatography/
Photodiode
Array
Method
Another
analytical
method
used
in
the
NAWQA
program
for
the
analysis
of
carbaryl
in
water
samples
is
the
LC/
PDA
method
described
by
Werner,
et
al.,
1996.
This
method
was
used
for
the
analysis
of
carbaryl
in
a
limited
number
of
samples
as
noted
above.
In
this
multi
residue
method,
the
analytes
are
first
removed
from
the
water
sample
by
sorption
on
a
Carbopak
B
solid
phase
extraction
cartridge
and
are
subsequently
eluted
from
the
solid
phase,
separated
by
HPLC
and
quantified
by
light
absorption
using
a
photodiode
array
detector.
The
identity
of
each
analyte
is
confirmed
by
the
appropriate
combination
of
retention
time
and
light
absorption
characteristics.
The
recoveries
for
carbaryl
spiked
at
different
levels
into
three
water
samples
and
analyzed
by
this
method
is
shown
in
Table
7
The
recoveries
ranged
from
58%
to
84%
for
the
different
water
and
spiking
levels.
Laboratory
control
spikes
in
organic
free
water
resulted
in
a
mean
recovery
of
61%
over
a
two
year
sampling
period.
These
results
indicate
reasonable
levels
of
carbaryl
recovery
from
each
of
the
different
types
of
water
evaluated
for
the
method.
Table
7.
Recovery
and
Precision
for
Multiple
Determinations
of
Carbaryl
in
LC/
PDA
Method
for
Carbaryl
Spiked
in
Different
Water
Samples
Water
type
Spike
Concentration
(
µ
g/
L)
Mean
Recovery
(%)
MDL
Calculated
Organic
Free
0.1
82
0.
008
Organic
Free
1.0
70
Surface
A
0.1
84
0.
016
Surface
A
1.0
84
Ground
B
0.1
58
0.
018
Ground
B
1.0
64
Organic
Free
0.5
61
C
A
Surface
water
was
collected
from
the
South
Platte
River
at
Englewood,
Colorado.
B
Ground
water
was
collected
from
Jefferson
County,
Colorado
(Arvada
Well
14).
C
National
Water
Quality
Laboratory
results
produced
using
5
operators
and
7
instruments
over
2
years
(about
350
data
points).
Summary
of
Surface
Water
Data
from
the
California
DPR
Surface
Water
Database
In
Section
5
pages
34
to
37
EPA
has
summarized
surface
water
monitoring
data
from
various
sources.
One
source
not
included
in
this
discussion
is
the
California
Surface
Water
Monitoring
Database.
The
number
of
analyses
and
the
detections
of
carbaryl
residues
reported
in
the
database
are
summarized
in
Table
8.
Carbaryl
was
detected
at
levels
above
the
LOQ
in
only
5.1%
of
the
2,690
samples
analyzed.
The
mean
concentration
of
carbaryl
in
the
140
samples
above
the
LOQ
was
0.42
ppb.
The
highest
concentration
of
carbaryl
that
was
detected
was
8.4
ppb.
65
An
analysis
of
the
data
in
the
California
Department
of
Pesticide
Regulation's
surface
water
database
as
of
July
15,
2000
was
conducted
for
carbaryl.
The
following
summary
of
the
contents
of
the
database
is
adapted
from
information
provided
by
the
California
DPR.
The
database
contains
monitoring
results
for
pesticides
in
samples
taken
from
California
rivers,
creeks,
urban
streams,
agricultural
drains,
the
Delta,
and
urban
stormwater
runoff.
As
of
July
15,
2000,
the
database
contained
the
results
of
30
studies
conducted
by
federal,
state,
and
local
agencies,
private
industry,
and
an
environmental
group.
A
total
of
4,660
samples
were
taken
in
16
counties
from
January
1991
through
March
2000.
Each
record
in
the
database
is
the
result
of
one
analysis
for
a
pesticide
active
ingredient
or
breakdown
product.
The
database
contains
a
total
of
92,296
analytical
records.
Only
information
on
the
analytical
detection
of
carbaryl
in
these
water
samples
is
summarized
in
Table
8
below.
Table
8.
Carbaryl
Detections
Reported
in
California
DPR
Surface
Water
Monitoring
Database
Land
Use
Type
Number
of
Samples
<=
LOQ
>0.003
to
0.01
>0.01
to
0.1
ppb
>0.1
to
1
ppb
>1
ppb
No.
%
No.
%
No.
%
No.
%
No.
%
All
Samples
2690
2553
94.9
1
13
0.48
55
2.04
55
2.04
14
0.52
Concentrations
of
analytical
results
that
are
reported
below
the
limit
of
quantification
are
reported
as
a
zero
in
the
database
concentration
field.
The
LOQs
for
the
different
methods
used
to
generate
the
data
contained
in
the
database
ranged
from
0.003
to
0.5
µ
g/
L,
with
a
majority
of
the
samples
analyzed
with
an
LOQ
of
0.05
µ
g/
L
or
less
(Table
9)
.
Table
9.
Limits
of
Quantification
for
Carbaryl
Analytical
Methods
Reported
in
California
DPR
Surface
Water
Monitoring
Database
LOQ
(
µ
g/
L)
0.003
0.041
0.044
0.05
0.07
0.1
0.
5
Number
of
Samples
Analyzed
267
238
168
1353
92
53
146
66
2.
Ground
Water
Concentrations
In
Section
5
page
34
EPA
summarized
information
on
the
detection
of
carbaryl
in
groundwater
from
the
EPA
Pesticides
in
Groundwater
Database,
the
EPA
STORET
database
and
the
NAWQA
database.
Each
of
the
databases
shows
a
pattern
of
very
low
levels
of
carbaryl
detection
in
few
groundwater
resources.
These
analyses
confirm
several
statements
made
by
the
Agency
that
carbaryl
has
limited
potential
to
impact
groundwater
resources.
However,
on
page
2
of
the
Memorandum
issued
June
28,
2001,
in
conjunction
with
the
EFED
RED
chapter
for
carbaryl,
EPA
is
requiring
additional
information
on
"Surface
and
groundwater
monitoring
in
urban
and
suburban
use
areas
(non
guideline)."
Based
on
the
characteristics
of
carbaryl
and
the
available
data
demonstrating
limited
impact
of
carbaryl
on
ground
water
resources,
additional
studies
to
evaluate
the
potential
for
carbaryl
to
contaminate
groundwater
are
unnecessary
and
unwarranted.
Summary
of
Ground
Water
Data
from
the
NAWQA
Program
In
Section
5,
pages
33
34,
EPA
has
summarized
ground
water
monitoring
data
available
for
carbaryl.
The
database
that
contains
the
most
extensive
evaluation
of
the
impact
of
the
most
recent
uses
of
carbaryl
on
ground
water
is
the
NAWQA
database.
One
deficiency
of
the
NAWQA
program
is
that
samples
are
targeted
to
agricultural
and
urban
areas
but
not
to
areas
treated
with
the
specific
chemical
being
analyzed.
However,
given
the
use
patterns
of
carbaryl,
the
use
of
carbaryl
has
certainly
occurred
near
a
number
of
these
wells.
Another
deficiency
is
that
when
residues
are
found,
that
while
they
may
be
representative
of
residues
in
ground
water,
they
may
not
be
representative
of
residues
in
ground
water
used
for
drinking
water
due
to
the
location
of
the
sampled
wells
relative
to
potable
drinking
water
wells.
EPA
cited
a
1998
review
of
the
NAWQA
database
by
Kolpin
and
stated:
"Carbaryl
was
detected
at
greater
than
the
detection
limit
(0.003
:
g/
L)
in
1.1
%
of
groundwater
samples
from
1034
sites
across
the
U.
S.
by
U.
S.
G.
S.
NAQWA
(sic)
program.
The
maximum
observed
concentration
was
0.021
:
g/
L."
This
1998
analysis
has
been
extended
by
additional
study
data
collected
by
the
NAWQA
program.
The
additional
data
continue
to
show
a
limited
number
of
low
level
detections
of
carbaryl
in
ground
water
samples.
Table
10
below
summarizes
a
more
recent
provisional
review
by
Kolpin
(2001)
of
the
updated
NAWQA
database.
Not
all
of
the
water
samples
were
used
to
calculate
the
summary
statistics
as
noted
by
Kolpin:
"To
preclude
bias
in
these
summary
statistics
from
wells
that
were
sampled
more
than
once,
the
data
set
was
condensed
such
that
each
well
had
a
single
pesticide
analysis.
This
generally
was
the
first
sample
collected.
However,
subsequent
samples
were
selected
if
these
samples
contained
more
pesticide
data
(i.
e.,
a
larger
number
of
pesticides
were
analyzed).
Wells
that
were
designed
to
be
a
part
of
both
a
land
use
study
and
a
major
aquifer
survey
were
used
in
each
summary.
67
Because
of
uncertainties
in
the
source
of
water
and
contributing
land
use
area,
springs
and
drains
were
excluded
from
these
summaries."
Table
10.
Carbaryl
Detections
Reported
in
Pesticides
in
Ground
Water
Update
(Kolpin,
2001)
Site
Type
Number
of
Samples
Carbaryl
Detection
Frequency
(%)
Maximum
Estimated
Concentration
(
µ
g/
L)
All
>=
0.01
(
µ
g/
L)
>=
0.05
(
µ
g/
L)
>=
0.10
(
µ
g/
L)
Agricultural
LandUse
Wells
1244
0.40
0.16
0.0
0.
0
0.019
Urban
Land
Use
Wells
634
2.1
1.
3
0.0
0.
0
0.031
Major
Aquifers
1849
0.59
0.54
0.05
0.05
0.539
68
REFERENCES
Burgos,
W.
D.,
J.
T.
Novak
and
D.
F.
Berry.
1996.
Reversible
Sorption
and
Irreversible
Binding
of
Naphthalene
and
Naphthol
to
Soil:
Elucidation
of
Processes.
Environ.
Sci.
Technol.,
30:
1205
1211.
Burgos,
W.
D.,
D.
F.
Berry,
A.
Bhandair,
and
J.
T.
Novak.
1999.
Impact
of
Soil
Chemical
Interactions
on
the
Bioavailability
of
Naphthalene
and
1
Naphthol.
Water
Research,
33:
3789
3795.
Hassett,
J.
J.,
W.
L.
Banwart,
S.
G.
Wood,
and
J.
C.
Means.
1981.
Sorption
of
naphthol:
Implications
concerning
the
limits
of
hydrophobic
sorption.
Soil
Sci.
Soc.
Am.
J
45(
1):
38
42.
Kolpin,
D.
W.
June
11,
2001.
Pesticides
in
Ground
Water,
Summary
statistics;
Results
of
the
National
Water
Quality
Assessment
Program
(NAWQA),
1992
1998.
Available
for
download
from
http://
water.
wr.
usgs.
gov/
pnsp/
pestgw/.
Larson,
S.
J.
June
11,
2001.
Pesticides
in
Streams,
Summary
statistics;
Results
of
the
National
Water
Quality
Assessment
Program
(NAWQA),
1992
1998.
Available
for
download
from
http://
water.
wr.
usgs.
gov/
pnsp/
pestsw/.
Martin,
J.
D.
October
27,
1999
.Quality
of
Pesticide
Data
for
Environmental
Water
Samples
Collected
for
the
National
Water
Quality
Assessment
Program,
1992
96
and
Examples
of
the
Use
of
Quality
Control
Information
in
Water
Quality
Assessments.
Available
for
review
at:
http://
water.
wr.
usgs.
gov/
pnsp/
rep/
qcsummary/
McCall,
P.,
D.
Laskowski,
R.
Swann,
and
H.
Dishburger.
1980.
Measurement
of
Sorption
Coefficients
of
Organic
Chemicals
and
Their
Use
in
Environmental
Fate
Analysis.
In:
Test
Protocols
for
Environmental
Fate
&
Movement
of
Toxicants.
Proceedings
of
a
Symposium,
Association
of
Official
Analytical
Chemists,
94th
Annual
Meeting,
October
21,
22,
1980.
pp
89
109.
Werner,
I.,
L.
A.
Denovic,
V.
Conner,
V.
De
Vlaming,
H.
Bailey
and
D.
E.
Hinton.
2000.
Insecticide
Caused
Toxicity
to
Ceriodaphnia
dubia
(Cladocera)
in
the
Sacramento
San
Joaquin
River
Delta,
California.
Environmental
Toxicology
and
Chemistry,
19:
215
227.
Werner,
S.
L.,
M.
R.
Burkhardt
and
S.
N.
DeRusseau.
1996.
METHODS
OF
ANALYSIS
BY
THE
U.
S.
GEOLOGICAL
SURVEY
NATIONAL
WATER
QUALITY
LABORATORY—
DETERMINATION
OF
PESTICIDES
IN
WATER
BY
CARBOPAK
B
SOLIDPHASE
EXTRACTION
AND
HIGH
PERFORMANCE
LIQUID
CHROMATOGRAPHY.
U.
S.
Geological
Survey
Open
File
Report
96
216,
42
pp.
Available
for
download
from
http://
wwwnwql.
cr.
usgs.
gov/
Public/
pubs/
OFR96
216/
OFR96
216.
html.
69
Zaugg,
S.
D.,
M.
W.
Sandstrom,
S.
G.
Smith
and
K.
M.
Fehlberg.
1995.
METHODS
OF
ANALYSIS
BY
THE
U.
S.
GEOLOGICAL
SURVEY
NATIONAL
WATER
QUALITY
LABORATORY—
DETERMINATION
OF
PESTICIDES
IN
WATER
BY
C
18
SOLID
PHASE
EXTRACTION
AND
CAPILLARY
COLUMN
GAS
CHROMATOGRAPHY/
MASS
SPECTROMETRY
WITH
SELECTED
ION
MONITORING.
U.
S.
Geological
Survey
OpenFile
Report
95
181,
49
pp.
Available
for
download
from
http://
wwwnwql.
cr.
usgs.
gov/
Public/
pubs/
OFR95
181/
OFR95
181.
html.
70
Confidential
Business
Attachment
APPENDIX
1
Surface
Water
Monitoring
for
Residues
of
Carbaryl
in
High
Use
Areas
of
the
United
States
(Stone
Environmental,
Inc.
Report
#99
1005
F)
(hard
copy
provided).
71
Confidential
Business
Attachment
APPENDIX
2
Calculation
of
County
Average
Carbaryl
Use
Rates
(hard
copy
provided)
| epa | 2024-06-07T20:31:42.452648 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0016/content.txt"
} |
EPA-HQ-OPP-2002-0138-0017 | Supporting & Related Material | "2002-07-31T04:00:00" | null | 1/
11/
01
Concerned
Citizen
Requests
Meeting
with
SRRD
about
Washington
State
SLN
Registration
of
Carbaryl.
A
concerned
citizen
from
Washington
State
has
requested
a
meeting
with
SRRD,
tentatively
scheduled
for
January
16th,
on
the
reregistration
of
carbaryl
and
its
use
on
oyster
beds
in
Washington
State
as
a
FIFRA
24(
c)
Special
Local
Need
(SLN)
registration.
The
concerned
citizen
lives
on
one
of
the
two
bays
affected
by
carbaryl
spraying
and
opposes
the
SLN
registration.
Concerns
include
spray
drift
of
carbaryl
onto
the
oyster
beds
of
residents
who
oppose
carbaryl,
lethality
to
nontarget
invertebrates
such
as
Dungeness
crabs,
and
the
general
impact
of
spraying
on
the
bays'
ecosystems.
An
area
tribe,
the
Shoal
Water
Tribe,
has
also
expressed
concerns
about
carbaryl
use
in
the
bay
and
in
nearby
cranberry
bogs.
The
bays'
oyster
farmers
have
been
spraying
carbaryl
since
1963
to
kill
burrowing
shrimp,
which
can
loosen
sediment
on
the
beds
and
suffocate
oyster
larvae
or
"seed."
Estimates
by
the
bays'
growers
association
in
1996
placed
the
annual
value
of
the
local
industry
at
$15
to
$30
million.
Carbaryl
spraying
on
oyster
beds
has
been
controversial
within
the
state
and
the
subject
of
many
studies,
including
studies
of
potential
impacts
on
endangered
species.
The
state
is
now
writing
a
draft
NPDES
permit
for
the
SLN
registration
of
carbaryl
in
response
to
the
Talent
Decision
by
the
9th
Circuit
Court
of
Appeals.
(Tony
Britten,
703
308
8179)
1/
18/
01
SRRD
Meets
with
Concerned
Citizen
about
Carbaryl
SLN
Use
on
WA
State
Oyster
Beds.
Carbaryl
(brand
name
SEVIN)
is
used
on
oyster
beds
in
two
Washington
State
bays
to
kill
species
of
burrowing
shrimp
that
loosen
sediment
and
cause
loss
of
oyster
crop.
A
concerned
Washington
State
citizen
who
opposes
this
SLN
use
met
with
SRRD
and
requested
information,
including:
(1)
any
administrative
procedures
available
for
aggrieved
citizens
to
request
removal
of
an
SLN
registration,
(2)
an
explanation
why
only
oysters
have
a
food
tolerance
when
other
seafood
products
from
the
bays
are
exposed
to
carbaryl,
and
(3)
whether
states
must
send
EPA
new
studies
that
show
adverse
effects
from
SLN
use.
FEAD
also
met
with
the
citizen
to
discuss
the
Talent
court
decision
and
a
state
NPDES
permit
being
issued
for
the
SLN
use.
The
citizen
also
stated
a
desire
to
meet
with
Aventis,
the
manufacturer
of
SEVIN,
to
discuss
concerns
about
the
SLN
use.
(Tony
Britten,
308
8179).
| epa | 2024-06-07T20:31:42.499356 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0017/content.txt"
} |
EPA-HQ-OPP-2002-0138-0018 | Supporting & Related Material | "2002-07-31T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES,
AND
TOXIC
SUBSTANCES
DP
Barcode:
D276945
PCCode:
056801
Date:
August
17,
2002
MEMORANDUM:
SUBJECT:
Response
to
Registrant's
30
day
Error
Correction
Comments
on
the
EFED
Risk
Assessment
Chapter
in
Support
of
the
Reregistration
Eligibility
Decision
(RED)
on
Carbaryl
To:
Anthony
Britten,
PM
Team
Reviewer
Betty
Shackleford,
Product
Manager
53
Special
Review
and
Reregistration
Division
(7508C)
FROM:
E.
Laurence
Libelo,
Ph.
D.,
Environmental
Engineer
Thomas
Steeger,
Ph.
D.,
Senior
Biologist
Environmental
Risk
Branch
IV
Environmental
Fate
and
Effects
Division
(7507C)
Angel
Chiri,
Ph.
D.,
Biologist
Biological
and
Economic
Assessment
Division
THRU:
Betsy
Behl,
Chief
ERB
IV/
EFED
(7507C)
The
Environmental
Fate
and
Effects
Division
(EFED)
has
reviewed
the
registrant
30
day
(Phase
I)
error
response
from
Aventis
CropScience
entitled
"Review
of
the
Draft
Environmental
Fate
and
Ecological
Risk
Assessment
of
the
Reregistration
of
Carbaryl."
EFED
has
revised
its
risk
assessment
for
the
reregistration
eligibility
decision
(RED)
and
is
attaching
the
revised
document.
Revisions
to
the
chapter
(identified
below)
reflect
only
those
instances
where
an
actual
error
was
identified.
Comments
from
the
registrant
that
did
not
identify
an
actual
error
but
rather
were
editorial
in
nature
will
be
addressed
after
the
public
comment
period
(Phase
II)
has
ended.
However,
several
generic
issues
were
raised
by
the
registrant
that
EFED
would
like
to
comment
on.
These
include
endocrine
disruption,
the
use
of
open
literature
to
supplement
core
data
submissions,
status
of
Aventis'
water
monitoring
studies,
and
the
role
of
new
data
submissions
in
characterizing
risk
in
the
current
version
of
the
RED.
Endocrine
Disruption
The
risk
assessment
chapter
is
not
intended
to
resolve
the
endocrine
disrupting
potential
of
carbaryl.
Rather,
the
chapter
summarizes
available
ecological
effect
data;
EFED
believes
there
are
sufficient
data
to
raise
concern
regarding
the
endocrine
disrupting
potential
of
carbaryl.
EFED
is
required
to
identify
effects
that
it
believes
are
consistent
with
responses
to
endocrine
mediated
pathways.
Those
chemicals
identified
as
potential
endocrine
disruptors
such
as
carbaryl,
will
likely
be
subject
to
more
refined
testing
for
such
effects
once
the
appropriate
testing
procedures
have
been
2
identified.
However,
at
this
stage
of
the
process
EFED
is
simply
identifying
potential
endocrine
disruptors.
Open
Literature
Open
literature
studies
are
not
intended
to
fulfill
guideline
data
requirements
but
rather
they
are
intended
to
help
reduce
uncertainty
and
support
concerns
regarding
risk.
Additionally,
EFED
relies
on
open
literature
from
peer
reviewed
journals
that
require
proposed
publications
to
undergo
the
scrutiny
of
review
prior
to
release
to
the
general
public.
The
registrant
contends
that
toxicity
data
obtained
from
published
literature
are
".
.
.
at
times
at
least
questionable
and
other
times
does
not
fulfill
the
requirements
set
by
EPA
for
studies
submitted
by
the
registrant.
Data
of
such
poor
quality
should
not
be
used
as
key
information
in
the
risk
assessment."
EFED
has
routinely
relied
on
published
literature
particularly
in
cases
where
there
are
insufficient
core
data
and/
or
the
existing
data
introduce
considerable
uncertainty
into
the
risk
assessment
process.
In
general,
published
literature
is
drawn
from
peer
reviewed
journals;
while
EFED
does
not
have
access
to
the
original
data
on
which
these
studies
are
based,
it
is
assumed
that
the
study
conclusions
have
undergone
some
degree
of
scientific
scrutiny
to
warrant
publication.
Status
of
Aventis'
Drinking
Water
Monitoring
Studies
The
registrant
makes
repeated
reference
to
the
drinking
water
monitoring
study
data
that
were
submitted.
The
study
is
very
limited
in
scope
and
it
is
unclear
how
sites
that
were
monitored
relate
to
locations
where
carbaryl
has
been
used
nationally.
It
is
extremely
unlikely
that
this
study
sampled
peak
concentrations.
In
addition,
the
study
design
did
not
allow
EFED
to
evaluate
the
effect
of
drinking
water
treatment
on
carbaryl
concentrations.
The
study
is
also
of
only
limited
usefulness
for
determining
concentrations
in
surface
water
for
use
in
ecological
exposure
assessment.
Water
bodies
represented
in
the
study
are
generally
larger
then
those
of
concern
for
ecological
exposure.
The
limitations
on
this
study
have
been
discussed
in
the
reviews
of
the
study
interim
reports.
Additional
Data
In
several
instances,
the
registrant
references
recently
submitted
data
as
addressing
uncertainties
characterized
in
the
RED.
Since
these
data
were
not
available
when
the
draft
RED
was
written,
they
were
not
captured
in
the
RED.
Depending
on
the
quality
of
the
new
data,
they
may
be
included
in
the
RED
after
they
have
been
reviewed.
However,
the
30
day
error
response
phase
is
not
intended
to
represent
an
opportunity
to
submit
additional
data.
Additionally,
if
data
are
provided
that
demonstrate
that
certain
environmental
fate
and
ecological
effects
endpoints
might
be
substantially
different
than
those
used
in
the
RED,
it
does
not
discount
the
reliability
and/
or
utility
of
the
original
studies.
For
example,
if
the
newly
submitted
2
generation
rat
study
provides
a
no
observe
effect
concentration
which
is
significantly
less
sensitive
than
the
endpoint
used
from
the
rat
developmental
study,
then
it
is
likely
that
EFED
would
continue
to
use
the
results
of
the
original
developmental
study,
i.
e.,
the
most
sensitive
endpoint,
to
evaluate
chronic
toxicity.
In
the
attached
document
(Attachment
A)
each
of
the
registrant's
comments
is
addressed.
The
attachment
is
in
three
sections,
i.
e.,
General
Comments,
Transmittal
and
RED
Document
Line
by
Line
Review
of
the
Carbaryl
RED
Chapter,
and
Discussion.
In
the
line
by
line
review,
the
registrant
cites
specific
EPA
comments
and
then
provides
their
response
to
the
comment.
In
all
three
sections,
the
EFED
response
to
discussions
and/
or
comments
is
entitled
"EFED
Response".
In
many
cases
the
registrant
has
provided
constructive
comments
on
the
EFED
science
chapter
and
has
helped
to
assure
the
document's
accuracy.
Overall
though,
the
registrant's
comments
have
not
affected
the
basic
3
concerns
and
uncertainties
identified
in
environmental
fate
and
ecological
effects
assessment
of
carbaryl.
4
Attachment
A.
EFED
Responses
to
30
day
Error
Correction
Comments
by
Registrant
CARBARYL
PC
Code
No.
056801;
Case
0080
Review
of
the
Draft
Environmental
Fate
and
Ecological
Risk
Assessment
for
the
Reregistration
of
Carbaryl
August
6,
2001
Aventis
CropScience
P.
O.
Box
12014,
2
T.
W.
Alexander
Drive
Research
Triangle
Park,
NC
27709
5
General
Comments
The
EFED
draft
chapter
of
the
carbaryl
RED
is
very
thorough
using
a
wealth
of
references.
The
use
of
published
literature
over
submitted
data
is
significant.
The
quality
of
the
published
literature
is
at
times
at
least
questionable
and
other
times
does
not
fulfill
the
requirements
set
by
EPA
for
studies
submitted
by
the
registrant
(e.
g.
thorough
description
of
test
conditions,
clear
identification
of
the
test
material,
analytical
verification,
GLP
etc.).
Data
of
such
poor
quality
should
not
be
used
as
key
information
in
the
risk
assessment.
For
the
30
day
response
not
all
literature
references
could
be
verified
or
the
quality
ascertained.
EFED
Response:
EFED
feels
that
all
available
relevant
information
should
be
used
in
evaluating
risk
of
pesticides
with
long
registration
histories.
As
in
other
risk
assessments
literature
data
were
used
to
supplement
and
to
help
evaluate
registrant
submitted
data.
Literature
data
were
also
used
when
required
core
data
were
not
submitted.
Literature
data
were
evaluated
by
EFED
scientists
prior
to
the
data's
inclusion
into
the
risk
assessment
and
data
of
questionable
validity
were
not
used.
There
is
a
high
level
of
redundancy
in
the
document
making
it
difficult
to
read.
Reducing
repetitions
to
a
minimum
would
facilitate
the
reading.
EFED
Response:
While
EFED
agrees
that
the
chapter
includes
some
redundancy,
this
does
not
represent
a
factual
error
in
the
document.
EFED
has
found
utility
in
repeatedly
emphasizing
certain
themes
to
underscore
concern
or
uncertainty.
We
believe
it
is
inappropriate
to
include
DERs
[data
evaluation
records]
in
the
RED
Chapters.
A
summary
of
study
findings
is
already
presented
in
the
document.
DERs
should
be
made
available
to
the
public
through
the
regular
procedure
under
the
Freedom
of
Information
Act
after
they
have
been
reviewed
and
cleared
for
confidential
business
information.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
that
DERs
should
be
made
available
to
the
public
under
the
Freedom
of
Information
Act
after
they
have
been
reviewed
and
cleared
for
confidential
business
information.
The
use
of
carbaryl
on
barley,
oats,
rye,
cotton,
and
livestock
are
cancelled
.
It
should
be
noted
that
Aventis
CropScience
labels
for
the
technical
materials
and
the
end
use
products
containing
carbaryl
were
amended
to
delete
these
uses.
The
Agency
has
already
approved
the
labeling
changes
(please
refer
to
HED
response
document,
Section
III
for
details).
6
EFED
Response:
The
cancelled
uses
have
been
removed.
The
document
reflects
uses
that
were
supported
at
the
time
the
chapter
was
written;
EFED
does
not
have
the
resources
to
revise
chapters
to
remain
consistent
with
current
mitigation
measures;
however
the
chapter
does
provide
a
better
understanding
of
why
certain
mitigation
agreements
were
reached.
Aventis
CropScience
will
no
longer
support
the
use
of
carbaryl
on
poultry
(direct
application
and
poultry
quarters
treatment).
We
will
shortly
submit
a
request
for
cancellation
of
these
uses
in
accordance
with
section
6(
f)(
1)
of
the
Federal
Insecticide,
Fungicide
and
Rodenticide
Act
(FIFRA)
(please
refer
to
HED
response
document,
Section
III
for
details).
Aventis
CropScience
is
in
the
process
of
conducting,
or
has
scheduled,
studies
relevant
to
the
refinement
of
the
environmental
risk
assessments
for
carbaryl
and
the
major
degradate
1
naphthol.
These
studies
are
as
follows:
C
Rate
and
Route
of
Aerobic
Degradation
in
Soils.
These
studies
have
been
initiated
with
parent
carbaryl
applied
to
four
diverse
U.
S.
soils.
The
data
are
intended
to
provide
additional
half
life
determinations
for
parent
carbaryl
and
the
major
degradate
1
naphthol.
Expected
completion
date:
March
2002
C
Aerobic
Aquatic
Metabolism
in
Two
Water/
Sediment
Systems.
These
studies
have
been
initiated
with
parent
carbaryl
applied
to
two
distinct
U.
S.
water/
sediment
systems.
The
data
are
intended
to
provide
additional
half
life
determinations
for
parent
carbaryl
and
the
major
degradate
1
naphthol.
In
addition,
further
identification
of
additional
degradation
products
is
anticipated.
Expected
completion
date:
March
2002
C
Adsorption
and
Desorption
of
1
Napthol
to
five
soils.
This
study
has
been
scheduled
to
evaluate
the
adsorption
and
desorption
of
the
major
carbaryl
degradate
to
five
soils/
sediment.
The
data
are
intended
to
provide
information
necessary
to
evaluate
the
environmental
risks
from
1
naphthol
in
standard
models.
Expected
completion
date:
March
2002
EFED
Response:
These
studies
will
be
reviewed
and
evaluated
when
they
are
received
and
if
the
studies
are
determined
to
be
scientifically
valid,
they
will
be
used
in
future
assessments.
For
the
reregistration
process
in
the
EU,
Aventis
CropScience
is
in
the
process
of
conducting,
or
has
scheduled,
studies
relevant
to
the
refinement
of
the
ecotoxicological
risk
assessments
for
carbaryl
and
the
major
degradate
1
naphthol.
These
studies
are
as
follows:
Studies
with
Carbaryl:
Acute
oral
LD50
in
mallard
ducks
Dynamic
acute
LC50
in
bluegill
sunfish
Acute
toxicity
in
Daphnia
7
Acute
toxicity
in
Chironomus
riparius
Toxicity
in
Selenastrum
capricornutum
Acute
oral
and
contact
toxicity
in
honeybees
14
d
toxicity
in
earthworms
Effects
on
soil
microorganisms
(nitrification/
carbon
cycle)
Effect
on
sewage
treatment
Studies
with
1
naphthol
Early
life
stage
study
in
fathead
minnow
Acute
toxicity
in
Daphnia
Acute
toxicity
in
Daphnia
in
presence
of
sediment
Chronic
toxicity
in
Daphnia
14
d
toxicity
in
earthworms
Formulated
Product
Vegetative
Vigor
Toxicity
in
Selenastrum
capricornutum
Acute
oral
and
contact
toxicity
in
honeybees
Effect
on
non
target
arthropods
14
d
toxicity
in
earthworms
Effects
on
soil
microorganisms
(nitrification/
carbon
cycle)
Ecotoxicological
Risk
Assessments
Aventis
has
pointed
out
several
errors
in
the
PRZM
input
parameters
(see
comments
made
to
Tables
5
and
6
of
the
draft
RED),
overly
conservative
estimates
of
foliar
dissipation
half
lives
and
changes
in
ecotoxicology
study
endpoints.
This
indicates
that
a
re
calculation
of
the
EECs
and
risk
quotients
are
warranted
in
a
number
of
instances.
EFED
Response:
EFED
has
reviewed
the
estimated
environmental
concentrations
[EECs]
and
does
not
agree
with
Aventis'
perspective
on
PRZM
input
parameters.
Specific
comments
are
addressed
in
the
appropriate
sections
below.
Endocrine
Disruption
Reports
in
the
open
literature
on
the
reproductive
effects
of
carbaryl
in
wild
mammals
are
at
best
ambivalent.
The
recently
submitted
2
generation
study
in
rats
demonstrates
the
absence
of
reproductive
effects.
As
EPA
pointed
out,
findings
reported
in
the
literature
were
made
at
concentrations
well
above
the
highest
peak
concentration
modeled.
Therefore
these
findings
are
irrelevant
for
a
risk
assessment
and
at
the
current
stage
of
discussion
about
endocrine
disruption.
If
the
concern
about
the
endocrine
potential
of
carbaryl
persists,
the
issue
should
be
revisited
once
the
Agency's
endocrine
disrupter
screening
and
testing
program
as
well
as
a
policy
on
how
to
8
incorporate
positive
findings
into
an
ecological
risk
assessment
have
been
fully
developed.
EFED
Response:
The
ecological
risk
assessment
does
not
conclude
that
carbaryl
is
an
endocrine
disrupter.
EFED
has
cited
open
literature
and
has
noted
effects
in
chronic
reproduction
studies
that
are
consistent
with
endocrine
mediated
effects.
EFED
is
uncertain
regarding
the
endocrine
disrupting
capacity
of
carbaryl
and
is
therefore
requesting
additional
data
when
the
appropriate
testing
procedures
have
been
identified.
Mobility
The
classification
of
carbaryl
as
mobile
to
very
mobile
is
inconsistent
with
measured
Koc
values
of
177
to
249
(MRID
43259301).
According
to
the
widely
used
classification
scheme
of
McCall,
et
al.
(1980)
wherein
Koc
values
between
150
and
500
denote
medium
mobility
in
soil,
carbaryl
would
be
classified
as
having
medium
mobility
in
most
soils.
This
classification
of
medium
mobility
is
further
supported
by
the
acceptable
column
leaching
study
(MRID
43320701)
in
which
aged
carbaryl
residues
were
only
slightly
mobile
in
a
number
of
soils.
The
mobility
of
carbaryl
would
be
expected
to
be
higher
in
sandy
soils
or
in
soils
of
low
organic
matter.
EFED
Response:
There
are
a
number
of
classification
schemes
available
and
EFED
does
not
agree
that
Macall
et
al
1980
is
the
definitive
one.
However,
EFED
has
revised
the
chapter
to
read
that
"Carbaryl
is
considered
to
be
moderately
mobile
in
soils."
1
Napthol
Fate
and
Transport
The
Agency
is
requiring
additional
information
on
the
persistence
and
mobility
of
1
naphthol,
a
major
environmental
degradate
of
carbaryl.
However,
a
half
life
for
1
naphthol
of
less
than
1
day
can
be
calculated
from
the
carbaryl
aerobic
soil
metabolism
study
(MRID
42785101).
The
data
from
this
study
demonstrate
that
under
aerobic
soil
conditions
the
formation
and
decline
of
1
naphthol,
starting
from
parent
carbaryl,
is
complete
in
less
than
14
days.
This
half
life
can
be
used
for
preliminary
environmental
fate
modeling
to
estimate
EECs
for
1
naphthol.
EFED
Response:
Based
on
the
aerobic
soil
metabolism
study
of
carbaryl
it
does
appear
that
1
naphthol
degrades
rapidly.
However,
there
are
a
number
of
processes
occurring
simultaneously
in
the
test
system.
It
is
not
possible
to
solve
for
the
multiple
degradation
and
sorption/
desorption
rate
constants
from
the
limited
data
provided.
The
registrant
is
encouraged
to
provide
additional
data
to
resolve
this
uncertainty.
The
EPA
suggested
that
1
naphthol
is
not
strongly
sorbed
to
soil.
Additional
information
available
in
the
literature
demonstrates
that
the
sorption
of
1
naphthol
to
soil
is
stronger
than
that
seen
for
9
carbaryl
itself.
Hassett
et
al.
(1981)
has
demonstrated
that
the
sorption
of
1
naphthol
was
the
result
of
sorption
to
organic
carbon
resulting
in
Koc
values
between
431
and
15,618.
These
data
indicate
that
1
naphthol
is
less
mobile
and
less
susceptible
to
leaching
than
carbaryl
itself,
and
they
demonstrate
that
at
least
a
portion
of
the
1
naphthol
residue
is
tightly
sorbed
to
soil
constituents.
(A
copy
of
this
article
is
being
submitted
with
the
response
to
the
draft
RED.)
To
meet
the
requirement
for
information
on
the
adsorption
and
desorption
of
1
naphthol
by
the
Agency,
the
registrant
is
conducting
an
adsorption/
desorption
study
to
meet
the
163
1
guideline.
Study
results
should
be
available
for
submission
to
the
Agency
in
the
first
quarter
of
the
calendar
year
2002.
EFED
Response:
EFED
will
review
the
data
on
the
mobility
of
1
naphthol
when
it
is
submitted.
EFED
agrees
that
literature
data
indicated
that
the
degradate
is
less
mobile
then
the
parent.
Surface
Water/
Drinking
Water
Aventis
disagrees
with
EPA
that
the
modeling
simulations
provide
a
conservative,
though
not
unreasonable,
estimate
on
possible
concentrations
in
drinking
water.
Drinking
water
concentrations
derived
from
PRZM/
EXAMS
greatly
overestimate
the
potential
exposure
to
carbaryl
in
drinking
water,
generally
by
several
orders
of
magnitude.
Results
from
the
drinking
water
monitoring
program
conducted
by
the
registrant
provides
a
`real
world'
assessment
of
the
potential
for
human
exposure
to
carbaryl
in
drinking
water
derived
from
surface
water.
EFED
Response:
EFED
has
reviewed
the
registrant's
drinking
water
survey,
and
has
discussed
its
limitations
in
the
RED
chapter
and
elsewhere.
The
study
is
very
limited
in
scope
and
it
is
unclear
how
sites
that
were
monitored
relate
to
locations
where
carbaryl
has
been
used
nationally.
It
is
extremely
unlikely
that
this
study
sampled
peak
concentrations.
Until
a
detailed
description
of
how
the
sampling
locations
were
chosen
and
how
those
sites
relate
to
the
rest
of
the
country
has
been
evaluated,
it
is
not
possible
to
use
this
small
scale
study
in
our
assessment.
This
information
was
submitted
as
part
of
the
registrant's
30
day
comment
period
response.
It
will
be
reviewed
along
with
other
submitted
data
and
included
in
future
risk
assessments.
Ground
Water
EPA
summarized
information
on
the
detection
of
carbaryl
in
groundwater
from
the
EPA
Pesticides
in
Groundwater
Database,
the
EPA
STORET
database
and
the
NAWQA
database.
Each
of
the
databases
shows
a
pattern
of
very
low
levels
of
carbaryl
detection
in
few
groundwater
resources.
These
analyses
confirm
several
statements
made
by
the
Agency
that
carbaryl
has
limited
potential
to
impact
groundwater
resources.
However,
on
page
2
of
the
Memorandum
issued
June
28,
2001,
in
conjunction
with
the
EFED
RED
chapter
for
carbaryl,
EPA
is
requiring
additional
information
on
"surface
and
groundwater
monitoring
in
urban
and
suburban
use
areas
(non
guideline)."
Based
on
the
characteristics
of
carbaryl
and
the
available
data
demonstrating
limited
impact
of
carbaryl
on
ground
water
resources,
additional
studies
to
evaluate
the
potential
for
carbaryl
to
contaminate
10
groundwater
are
unnecessary
and
unwarranted.
EFED
Response:
Carbaryl
use
in
agricultural
setting
is
expected
to
have
only
limited
impact
on
groundwater
resources.
However,
because
of
its
widespread
use
by
homeowners,
it
is
likely
that
groundwater
impacts
will
be
greatest
in
residential
settings.
EFED
does
not
require
additional
data
for
groundwater
contamination
evaluation
(e.
g.
prospective
groundwater
studies)
for
agricultural
uses
but
does
for
residential
use.
11
Line
by
Line
Review
of
the
Carbaryl
EFED
RED
Chapter
Transmittal
Document
Data
Gaps
Environmental
Fate
and
Transport
Page:
2
Paragraph:
1
Line:
1
EPA
comment:
Fate
information
on
the
degradation
product
1
naphthol
is
required.
1.
Mobility
–
adsorption
and
desorption
studies
for
the
1
naphthol
degradate
(163
1)
2.
Persistence
–
aerobic
soil
metabolism
study
on
1
naphthol
Aventis'
response:
Literature
data
(Hassett
et
al.
1981)
on
the
adsorption
of
1
naphthol
are
provided
in
this
response.
Aventis
is
in
the
process
of
conducting
an
additional
adsorption/
desorption
study
on
1
naphthol
and
intends
to
submit
study
data
to
EPA
by
March
2002.
The
degradation
of
1
naphthol
under
aerobic
soil
conditions
has
been
widely
reported
in
the
literature.
Several
citations
are
included
in
the
EPA
draft
RED.
The
half
life
of
1
naphthol
estimated
from
the
acceptable
aerobic
soil
persistence
study
on
carbaryl
(MRID
42785101)
is
less
than
1
day.
Aventis
is
conducting
additional
laboratory
aerobic
soil
degradation
studies
on
carbaryl
that
will
be
used
to
provide
additional
determinations
of
the
half
life
for
the
degradate
1
naphthol
and
satisfy
the
Agency's
requirement
for
data
on
the
persistence
of
1
naphthol.
Aventis
intends
to
submit
these
study
data
to
EPA
by
March
2002.
EFED
Response:
EPA
will
review
and
evaluate
the
new
data
when
it
is
submitted
and
will
incorporated
it
into
future
risk
assessments.
From
the
aerobic
soil
study
it
does
appear
that
1
naphthol
degrades
rapidly.
However,
there
are
a
number
of
processes
occurring
simultaneously
in
the
test
system,
and
it
is
not
possible
to
solve
for
the
multiple
degradation
and
sorption/
desorption
rate
constants
from
the
limited
data
provided.
Water
Resources
Page:
2
Paragraph:
3
and
4
EPA
comment:
"EFED
believes
that
adequate
data
are
available
to
support
the
conclusions
reached
for
carbaryl's
impact
on
surface
water
and
groundwater
quality
with
the
exceptions
noted
below.
Additional
information
is
needed
to
characterize
the
impact
of
the
degradate
1
naphthol
[in]
groundwater
and
surface
water.
ÿ
Surface
and
groundwater
monitoring
in
urban
and
suburban
use
areas
(non
guideline)"
are
required.
12
Aventis'
response:
The
surface
water
monitoring
program
conducted
by
Aventis
includes
monitoring
in
urban
and
suburban
use
areas.
Aventis
believes
that
the
need
for
information
on
the
degradate
1
naphthol
will
be
satisfied
by
the
aerobic
soil
and
adsorption/
desorption
data
that
will
be
submitted
to
the
Agency.
These
data
can
be
used
to
evaluate
the
availability
of
1
naphthol
using
established
EPA
modeling
guidelines.
The
Agency's
proposed
requirement
for
groundwater
monitoring
is
unnecessary
and
is
addressed
in
Aventis'
response
to
Agency
comments
in
the
draft
RED.
EFED
Response:
EFED
will
review
all
additional
data
when
they
are
submitted.
New
data
will
be
included
in
future
risk
assessments.
EFED
has
reviewed
this
small
scale
study
and
does
not
agree
with
the
registrant's
assessment.
The
limitations
of
the
study
have
been
described
in
the
RED
chapter.
Ecological
Effects
Data
requirement
Page:
2
EPA
comment:
The
ecological
toxicity
database
is
complete
except
for:
6.
Aquatic
Plant
Growth
Guideline
122
2
Aventis'
response:
The
data
requirement
should
be
deleted.
Aquatic
plant
growth
studies
were
submitted
to
the
Agency
in
1992.
An
October
04,
2000
OPP
Guideline
Status
Report
(Chemical
Review
Management
System)
lists
the
guideline
122
2
status
as
"Acceptable/
Satisfied".
The
studies
are:
MRID
No.
Title
Acceptability
Code
42372101
Lintott,
D.
(1992)
Carbaryl
Technical:
Acute
Toxicity
To
The
Freshwater
Blue
Green
Alga,
Anabaena
flos
aquae,
Under
Static
Test
Conditions:
Lab
Project
Number:
J9112004E.
Unpublished
Study
Prepared
By
Toxikon
Environmental
Sciences.
53
P.
June
25,
1992
Upgradable
42372102
Lintott,
D.
(1992)
Carbaryl
Technical:
Acute
Toxicity
To
Duckweed,
Lemna
gibba
G3,
Under
Static
Test
Conditions:
Lab
Project
Number:
J9112004G.
Unpublished
Study
Prepared
By
Toxikon
Environmental
Sciences.
53
P.
January
1,
1992
Upgradable
42372802
Lintott,
D.
(1992)
Carbaryl
Technical:
Acute
Toxicity
To
The
Freshwater
Green
Alga,
Selenastrum
capricornutum
Under
Static
Conditions:
Lab
Project
Number:
J9112004C.
Unpublished
Study
Prepared
By
Toxikon
Environmental
Sciences.
53
P.
June
9,
1992
Acceptable
MRID
No.
Title
Acceptability
Code
13
42431601
Lintott,
D.
(1992)
Carbaryl
Technical:
Acute
Toxicity
To
The
Freshwater
Diatom,
Navicula
pelliculosa,
Under
Static
Test
Conditions:
Lab
Project
Number:
J9112004F.
Unpublished
Study
Prepared
By
Toxikon
Environmental
Sciences.
52
P.
August
10,
1992
Acceptable
42431602
Lintott,
D.
(1992)
Carbaryl
Technical:
Acute
Toxicity
To
The
Saltwater
Diatom,
Skeletonema
costatum,
Under
Static
Test
Conditions:
Lab
Project
Number:
J9112004D.
Unpublished
Study
Prepared
By
Toxikon
Environmental
Sciences.
49
P.
August
10,
1992
Supplemental
EFED
Response:
EPA
requires
data
on
5
aquatic
plant
species.
Only
two
of
the
five
species
provided
data
that
were
classified
as
acceptable
and
as
having
fulfilled
guideline
test
requirements.
Therefore,
EFED
is
requesting
that
aquatic
plant
studies
are
repeated
following
EPA
guidelines.
Page:
2
EPA
comment:
The
ecological
toxicity
database
is
complete
except
for:
7.
Submission
of
a
FETOX
amphibian
toxicity
study
is
required.
Aventis'
response:
The
data
requirement
should
be
deleted.
From
the
published
results
it
is
evident
that
carbaryl
is
practically
non
toxic
to
the
bullfrog.
Effects
in
plain
leopard
frogs
are
reported
at
levels
well
above
environmental
concentrations.
These
results
were
obtained
testing
U.
S.
native
species.
In
the
proposed
FETOX
assay,
a
non
native
species
Xenopus
laevis
is
used.
This
African
species
is
unique
in
its
behavior.
Neither
the
species
nor
the
test
methods
are
suitable
for
ecotoxicological
purposes.
As
the
risk
to
amphibians
can
be
evaluated
from
the
studies
cited,
and
as
the
effects
are
only
at
levels
well
above
the
EEC,
this
study
should
not
be
required.
EFED
Response:
While
EFED
is
concerned
about
the
documented
effects
of
carbaryl
on
native
frogs,
it
will
not
require
the
FETOX
study
at
this
time.
However,
when
appropriate
test
methods
have
been
developed
for
demonstrating
endocrine
disrupting
effects,
EFED
will
request
that
carbaryl
undergo
these
tests
to
better
understand
the
developmental
toxicity
of
carbaryl.
14
Label
Information
Page:
3
EPA
comment:
For
terrestrial
and
residential
uses:
1.
"Do
not
apply
directly
to
water,
or
to
areas
where
surface
water
is
present
or
to
intertidal
areas
below
the
mean
high
water
mark.
Do
not
contaminate
water
when
disposing
of
equipment
washwater
or
rinsate."
Aventis'
response:
Similar
language
is
already
present
on
Aventis'
SEVIN
®
labels.
EFED
Response:
The
label
language
that
EFED
is
requesting
is
standard
language
that
is
consistent
with
the
risks
identified
for
this
chemical.
Page:
3
EPA
comment:
For
terrestrial
and
residential
uses:
3.
"This
product
may
contaminate
water
through
drift
of
spray
in
wind.
This
product
has
a
high
potential
for
runoff
for
several
days
after
application
after
application
(sic).
Poorly
draining
soils
and
soils
with
shallow
water
tables
are
more
prone
to
produce
runoff
that
contains
this
product.
Household
labels
–
Avoid
applying
this
product
to
ditches,
swales,
and
drainage
ways.
Runoff
of
this
product
will
be
reduced
by
avoiding
applications
when
rainfall
is
forecasted
to
occur
within
48
hours.
Agricultural
Label
–
A
level,
well
maintained
vegetative
buffer
strip
between
areas
to
which
this
product
is
applied
and
surface
water
features
such
as
ponds,
streams,
and
springs
will
reduce
the
potential
for
contamination
of
water
from
rainfall
runoff.
Runoff
of
this
product
will
be
reduced
by
avoiding
applications
when
rainfall
is
forecasted
to
occur
within
48
hours."
Aventis'
response:
Aventis
would
like
to
further
discuss
appropriate
label
language
with
the
Agency.
However,
it
should
be
noted
that
light
to
moderate
rainfall
(or
irrigation)
after
application
will
also
help
move
carbaryl
residues
deeper
into
the
soil,
thus
making
them
less
susceptible
to
runoff.
The
language
in
the
last
sentence
should
be
changed
to
read,
"…
when
heavy
rainfall
is….".
15
EFED
Response:
EFED
believes
that
it
is
difficult
to
predict
rate
at
which
rain
will
fall
and
that
the
degree
of
runoff
from
or
penetration
into
soil
relative
to
the
amount
of
rainfall
depends
on
the
consistency
of
the
soil.
The
recommended
label
language
is
standard.
This
is
not
an
error.
Further
discussion
on
this
topic
is
more
appropriate
in
a
later
phase
of
the
reregistration
process.
Page:
3
EPA
comment:
For
terrestrial
and
residential
uses:
4.
This
pesticide
is
toxic
to
fish
and
aquatic
invertebrates.
Aventis'
response:
Aventis'
SEVIN
labels
currently
state
"This
product
is
extremely
toxic
to
aquatic
and
estuarine
invertebrates."
EFED
Response:
EFED
has
requested
label
language
to
mitigate
risks
to
both
freshwater
and
estuarine/
marine
fish
and
invertebrates.
Page:
3
EPA
comment:
For
terrestrial
and
residential
uses:
5.
This
product
is
highly
toxic
to
bees
exposed
to
direct
treatment
or
residues
on
blooming
crops
or
weeds.
Do
not
apply
this
product
or
allow
it
to
drift
to
blooming
crops
or
weeds
if
bees
are
visiting
the
treatment
area.
Aventis'
response:
Aventis'
SEVIN
labels
currently
contain
similar
language.
EFED
Response:
The
label
language
that
EFED
has
requested
is
intended
to
emphasize
the
risk
to
bees
when
plants
are
blooming.
16
Draft
RED
Document
1.0
Summary
and
Environmental
Risk
Conclusions
Risk
to
Terrestrial
Organisms
Page:
1
Paragraph:
4
Line:
2
EPA
comment:
As
discussed
in
pp.
44
45
and
in
Appendix
D.
Aventis'
response:
The
mammalian
risk
quotients
are
discussed
on
pages
48
to
50
and
in
Appendix
C,
not
as
described
in
this
text.
EFED
Response:
EFED
concurs
with
the
registrant's
comments.
The
references
to
specific
pages
and
to
the
appendix
have
been
deleted.
Fate
and
Water
Assessment
Page:
3
Paragraph:
5
Line:
3
EPA
comment:
…in
the
U.
S.
G.
S
NAQWA
program.
NAQWA…
Aventis'
response:
The
abbreviation
for
the
U.
S.
G.
S.
program
is
NAWQA
EFED
Response:
EFED
concurs
with
the
registrant's
comment
and
has
corrected
the
references
to
NAWQA
acronym
throughout
the
document.
Page:
5
Paragraph:
1
Line:
7
EPA
comment:
…estimate
of
possible
concentrations
drinking
water.
Aventis'
response:
missing
word
–
…concentrations
"in"
drinking…
17
EFED
Response:
EFED
concurs
with
the
registrant's
comment
and
has
included
the
word
"in".
Page:
5
Paragraph:
4
Line:
4
EPA
comment:
…hydrolyzes
in
neutral
(half
life
=
12
days)
and
alkaline
environments
(pH
9
half
life
=
3.2).
Aventis'
response:
Missing
units
of
after
second
half
life.
The
units
are
hours,
so
"=
3.2
hours)".
EFED
Response:
EFED
concurs
with
the
registrant's
comment
and
has
included
the
proper
units,
i.
e.,
hours.
Page:
5
Paragraph:
4
Line:
5
EPA
comment:
…photolysis
in
water
with
a
half
life
of
21
days
Aventis'
response:
this
is
for
photolysis
in
sterile
water,
not
microbially
active
water,
so
the
phrase
would
be
more
precise
as
"…
photolysis
in
sterile
water…".
EFED
Response:
EFED
concurs
with
the
registrant's
comment
and
has
changed
the
wording
to
read
"Carbaryl
is
degraded
by
abiotic
photolysis
.
.
.."
Page:
5
Paragraph:
4
Line:
last
EPA
comment:
(Kf
=1.7
to
3.2).
Aventis'
response:
The
upper
value
Kf
for
carbaryl
should
be
listed
as
3.5
as
referenced
by
EPA
elsewhere
(e.
g.
Table
3,
page
20)
in
the
document.
EFED
Response:
EFED
concurs
with
the
registrant's
comment
and
has
changed
the
range
of
Kf
to
read
1.7
–
3.5.
18
2.0
Introduction
Page:
6
Paragraph:
2
Line:
1
3
EPA
comment:
Carbaryl
(1
naphthyl
N
methylcarbamate)
is
a
broad
spectrum
carbamate
insecticide
and
acaricide
registered
for
control
of
over
300
species
of
insects
and
mites
on
over
100
crop
and
noncrop
use
sites,
including
homeowner
uses;
pet,
poultry,
and
livestock
uses;…
Aventis'
response:
Carbaryl
is
no
longer
registered
for
use
on
livestock.
Aventis
CropScience
will
not
support
the
reregistration
of
the
use
on
poultry
(direct
application
and
poultry
quarters
treatment).
We
will
shortly
submit
a
request
for
cancellation
of
this
use
in
accordance
with
section
6(
f)(
1)
of
the
Federal
Insecticide,
Fungicide
and
Rodenticide
Act
(FIFRA).
EFED
Response:
At
this
time,
carbaryl
is
registered
for
use
on
livestock.
When
the
cancellation
is
processed
the
wording
will
be
changed
for
future
risk
assessments.
Page:
6
Paragraph:
3
Line:
2
3
EPA
comment:
Approximately
2.5
million
pounds
of
carbaryl
are
applied
annually
in
the
U.
S.
A
map
showing
the
widespread
use
of
carbaryl
in
agriculture
is
shown
in
figure
1.
Aventis'
response:
Summation
of
the
data
in
Figure
1
gives
a
total
of
approximately
3.3
million
pounds
of
carbaryl.
Both
the
2.5
and
3.3
million
pound
figures
are
inconsistent
with
the
value
of
4
million
pounds
cited
on
page
35.
The
2.5
million
pounds
is
an
average
of
usage
over
1987
to
1996
developed
in
a
memo
by
Frank
Hernandez,
July
21,
1998.
The
value
of
2.5
million
pounds
in
the
text
should
be
qualified
with
the
additional
information
on
the
fact
that
it
is
an
average
for
usage
over
1987
to
1996
and
is
not
a
value
for
a
single
year.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised.
Page:
7
Paragraph:
1
Line:
3
4
EPA
comment:
Carbaryl
is
also
used
extensively
for
residential
and
other
non
agricultural
uses,
being
the
second
most
commonly
insecticide
(sic)
used
in
the
home.
19
Aventis'
response:
Carbaryl
is
not
registered
for
use
inside
homes.
It
is
registered
for
use
outdoors
in
the
lawn
and
garden
around
homes.
In
addition,
an
evaluation
of
the
Vista
(Triad)
data
for
the
last
seasonal
year
from
October
1999
to
September
2000
shows
retail
sales
for
carbaryl
at
18.7
million
dollars.
Carbaryl
is
listed
as
number
7
based
on
retail
sales
behind
other
active
ingredients
such
as
chlorpyrifos,
diazinon,
imidacloprid,
hydramethylnon
and
tralomethrin.
Therefore
this
sentence
would
be
more
appropriately
worded
as:
"Carbaryl
is
also
used
for
residential
and
other
non
agricultural
uses,
being
the
seventh
most
commonly
used
insecticide
around
the
home."
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised
to
read
"Carbaryl
is
also
used
for
residential
and
other
non
agricultural
uses,
being
the
seventh
most
commonly
used
insecticide
around
the
home."
Page:
7
Figure
1
EPA
comment:
Figure
2
Aventis'
response:
This
is
labeled
as
Figure
2
when
it
is
Figure
1
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
figure
showing
carbaryl
use
in
agriculture
has
been
relabeled
as
Figure
1.
3.0
Integrated
Risk
Characterization
Introduction
Page:
8
Paragraph:
1
Line:
last
EPA
comment:
Carbaryl
is
mobile
to
very
mobile
in
the
environment
(Kf
=1.7
to
3.2).
Aventis'
response:
The
upper
value
Kf
for
carbaryl
should
be
listed
as
3.5
as
referenced
by
EPA
elsewhere
(e.
g.
Table
3,
page
20)
in
the
document.
The
classification
of
carbaryl
as
mobile
to
very
mobile
is
inconsistent
with
measured
Koc
values
of
177
to
249.
According
to
the
widely
used
classification
scheme
of
McCall
et
al.
carbaryl
would
be
classified
as
having
medium
mobility
in
soil.
This
classification
of
medium
mobility
is
further
supported
by
the
20
acceptable
column
leaching
study
(MRID
43320701)
in
which
carbaryl
residues
were
only
slightly
mobile
in
a
number
of
soils.
EFED
Response:
There
are
many
classification
systems
available;
EPA
does
not
agree
that
the
McCall
et
al.
classification
is
the
definitive
classification.
For
example,
ASTM
(1996)
puts
Koc
of
177
in
the
medium
mobility
class
approaching
the
high
class.
EFED
has
however
revised
the
chapter
to
read
that
"Carbaryl
is
considered
to
be
moderately
mobile
in
soils."
Aquatic
Organisms
Page:
10,
Paragraph:
1,
Line:
13
EPA
comment:
Submission
of
a
FETOX
amphibian
toxicity
study
is
encouraged.
Aventis'
response:
The
data
requirement
should
be
deleted.
From
the
published
results
it
is
evident
that
carbaryl
is
practically
non
toxic
to
the
bullfrog.
Effects
in
plain
leopard
frogs
are
reported
at
levels
well
above
environmental
concentrations.
These
results
were
obtained
testing
U.
S.
native
species.
In
the
proposed
FETOX
assay
a
non
native
species
Xenopus
laevis
is
used.
This
African
species
is
unique
in
its
behavior.
Neither
the
species
nor
the
test
methods
are
suitable
for
ecotoxicological
purposes.
As
the
risk
to
amphibians
can
be
evaluated
from
the
studies
cited,
and
as
the
effects
are
only
at
levels
well
above
the
EEC,
this
study
should
not
be
required.
EFED
Response:
EFED
concurs
that
the
FETOX
assay
may
not
represent
the
most
appropriate
test
for
examining
the
effects
of
carbaryl
on
amphibian
behavior
and
development;
therefore,
EFED
is
not
requiring
the
study
at
this
time.
EFED
is
however
concerned
about
the
effects
of
carbaryl
on
amphibians
and
particularly
the
developmental
effects.
When
appropriate
test
methodologies
have
been
identified
for
examining
endocrine
disrupting
effects,
EFED
will
request
that
carbaryl
undergo
these
toxicity
tests.
Page:
10,
Paragraph:
3,
Line:
6/
7
EPA
comment:
…resulting
in
a
temporary
impairment
of
burying
behavior
and
increasing
exposure
to
predators.
Aventis'
response:
A
reference
for
this
statement
should
be
added.
21
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
appropriate
literature
citation,
i.
e.,
Pozorycki,
1999,
has
been
added.
Page:
11,
Paragraph:
2,
Line:
7
EPA
comment:
In
a
mesocosms
study,
at
carbaryl…
Aventis'
response:
Typographical
error.
Change
to
"In
a
mesocosm
study,
at
carbaryl…"
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
singular
form
of
the
noun
has
been
used.
Terrestrial
Organisms
Page:
12
Paragraph:
2
EPA
comment:
(use
of
rock
dove
LD50
)
Aventis'
response:
The
reference
cited
for
this
value
in
Table
1
of
Appendix
D
is
currently
not
available
to
Aventis.
Table
1
of
Appendix
D
gives
a
range
of
1000
–
3000
mg/
kg
for
the
LD50.
It
should
be
assured
that
1000
is
indeed
the
correct
value.
EFED
Response:
The
reference,
i.
e.,
Hudson,
R.
H.,
R.
K,
Tucker,
and
M.
A.
Haegele.
1984.
Handbook
of
toxicity
of
pesticides
to
wildlife.
U.
S.
Department
of
Interior,
Fish
and
Wildlife
Service
Resource
Publication
153.
Washington
DC,
is
routinely
cited
by
EFED.
The
acute
toxicity
value
(LD50
=1,000
mg/
Kg)
cited
for
rock
dove
represents
the
lower
95%
confidence
interval.
The
text
has
been
revised
to
note
that
this
number
represents
the
lower
95%
confidence
interval.
Page:
12
Paragraph:
3
Line:
3
6
EPA
comment:
On
a
chronic
basis,
the
NOAEC
is
300
ppm
for
the
mallard
duck,
based
on
adverse
reproduction
effects,
including
reduced
egg
production,
decreased
fertility,
increase
incidence
of
cracked
eggs,
increased
embryonic
mortality,
and
reduced
hatching
success.
22
Aventis'
response:
The
sentence
should
be
changed.
The
embryonic
mortality
and
the
hatching
success
were
not
different
from
the
control.
EFED
Response:
Although
the
data
evaluation
record
for
the
avian
reproduction
study
lists
increased
embryonic
mortality
and
reduced
hatching
success
as
significant
effects,
reference
to
these
two
effects
has
been
deleted
from
the
text
since
the
original
study
by
Fletcher
was
not
available
for
secondary
review.
However,
reduced
egg
production,
increased
incidence
of
cracked
eggs
and
decreased
fertility
are
reproductive
effects
that
support
EFED's
concerns
regarding
the
endocrine
disrupting
potential
of
carbaryl.
Page:
13
Paragraph:
1
Line:
1
EPA
comment:
…(
rat
LD50
=
307
mg/
kg)
Aventis'
response:
Typographical
error,
the
LD50
is
301
mg/
kg.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised
to
read
"(
rat
LD50
=
301
mg/
L)
.
.
."
Page:
13
Paragraph:
1
Line:
2
–
4
EPA
comment:
…based
on
decreased
fetal
body
weights
and
increased
incomplete
ossification
of
multiple
bones
in
the
laboratory
rat
(LOAEC
=
600
ppm,
NOAEC
=
80
ppm),
has
the
potential
for
mammalian
chronic
effects.
Aventis'
response:
A
new
chronic
reproduction
study
in
rats
has
been
submitted
by
Aventis.
This
study
is
more
relevant
for
an
ecological
risk
assessment
than
the
developmental
study
cited.
The
new
study
resulted
in
a
NOAEC
of
75
ppm.
EFED
Response:
At
the
time
the
ecological
risk
assessment
was
written,
the
more
recent
chronic
mammalian
toxicity
data
were
not
available
for
EFED
to
review.
The
difference
in
NOAEC
would
not
likely
impact
the
magnitude
of
the
chronic
risk
quotient
though.
23
Page:
13
Paragraph:
3
Line:
1
EPA
comment:
Information
available
in
the
open
literature
suggests
potential
reproduction
effects
of
carbaryl
on
mammals.
Aventis'
response:
The
sentence
should
be
changed
or
deleted.
The
literature
cited
in
the
paragraph
show
ambivalent
results.
While
some
references
seem
to
support
that
sentence,
other
references
do
not
substantiate
such
a
claim.
The
potential
for
reproductive
effects
in
mammals
is
evaluated
in
the
recently
submitted
2
generation
study
in
rats.
No
reproductive
effects
were
seen
in
that
guideline
study.
The
NOAEC
of
75
ppm
was
based
on
pup
mortality.
EFED
Response:
EFED
believes
that
the
chronic
effects
cited,
i.
e.,
reduced
reproduction,
disturbances
in
spermatogenesis,
increased
resorption
of
embryos,
increased
incidence
of
infertility
in
females
and
underdeveloped
testes
in
males,
are
serious
reproductive
effects
that
support
EFED's
concerns
regarding
the
endocrine
disrupting
potential
of
carbaryl.
Page:
13
Paragraph:
4
Line:
5
EPA
comment:
According
to
surveys
conducted
by
the
American
Beekeeping
Federation
and
the
Washington
State
Department
of
Agriculture,
carbaryl
is
one
of
the
pesticides
most
frequently
mentioned
as
being
associated
with
bee
kills.
Aventis'
response:
A
reference
should
be
provided
for
this
statement.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
two
literature
citations,
i.
e.,
Brandi
1997
and
Johansen
1997,
have
been
inserted
into
the
text.
Page:
14
Paragraph:
4
Line:
1
4
EPA
comment:
The
uses
of
carbaryl
on
crops
(corn,
cotton,
soybeans,
sorghum,
wheat,
barley,
oats,
and
rye),
forests
and
pasture/
rangeland
were
addressed
by
the
US
Fish
and
Wildlife
Service
(USFWS)
in
the
reinitiation
of
consultation
in
September
1989.
The
Service
found
jeopardy
to
a
total
of
86
species
–
6
amphibians,
47
freshwater
fish,
27
freshwater
mussels,
and
5
aquatic
crustaceans.
24
Aventis'
response:
The
use
of
carbaryl
on
barley,
oats,
rye,
and
cotton
has
been
cancelled.
It
should
be
noted
that
all
Aventis
CropScience
labels
for
the
technical
materials
and
the
end
use
products
containing
carbaryl
were
amended
to
delete
these
uses.
The
Agency
has
already
approved
the
labeling
changes.
Findings
from
the
assessment
made
by
the
USFWS
should
be
reevaluated
considering
the
cancellation
of
the
use
on
barley,
oats,
rye,
and
cotton.
EFED
Response:
EFED
does
not
have
the
resources
to
continually
revise
ecological
effects
assessments
each
time
mitigation
efforts
have
been
reached;
however,
the
chapter
has
been
revised
to
read
"
.
.
.
on
field
crops
(corn,
soybeans,
sorghum
wheat)
.
.
.."
Page:
14
Paragraph:
5
Line:
7
EPA
comment:
The
RPAs
and
RPMs
in
the
1989
B.
O.
may
need
to
be
reassessed…
Aventis'
response:
The
acronyms
used
should
be
explained.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised
to
read
"Reasonable
and
Prudent
Alternatives
(RPA)
.
.
.
Reasonable
and
Prudent
Measures
(RPM)
.
.
.."
The
acronym
B.
O.
has
been
replaced
with
the
term
Biological
Opinion.
Endocrine
Disruption
Concerns
Page:
15
Paragraph:
3
EPA
comment:
(Report
on
potential
endocrine
effects)
Aventis'
response:
The
paragraph
should
be
deleted.
As
EPA
pointed
out,
the
findings
reported
in
the
literature
were
made
at
concentrations
well
above
the
highest
peak
concentration
modeled.
Therefore
these
findings
are
irrelevant
for
a
risk
assessment
and
at
the
current
stage
of
discussion
about
endocrine
disruption.
If
the
concern
about
the
endocrine
potential
of
carbaryl
persists,
the
issue
should
be
revisited
once
the
Agency's
endocrine
disrupter
screening
and
testing
program,
as
well
as
a
policy
on
how
to
incorporate
positive
findings
into
an
ecological
risk
assessment
have
been
fully
developed.
25
EFED
Response:
The
ecological
risk
assessment
reports
on
a
broad
range
of
chronic
effects
in
both
terrestrial
and
aquatic
animals
that
support
EFED's
concerns
regarding
the
endocrine
disrupting
potential
of
carbaryl.
EFED
is
aware
of
the
fact
that
its
current
chronic
toxicity
tests
may
not
be
sensitive
indicators
of
endocrine
disrupting
effects,
therefore
the
Agency
has
to
rely
on
open
literature
to
address
this
uncertainty.
EFED
agrees
that
some
effects
are
reported
at
concentrations
that
may
not
be
environmentally
relevant;
however,
the
data
suggest
that
carbaryl
can
elicit
effects
that
are
consistent
with
a
chemical
acting
on
endocrine
mediated
pathways.
Therefore,
EFED
is
requesting
that
once
appropriate
methodologies
have
been
defined
for
screening
endocrine
disruption
effects,
carbaryl
should
undergo
such
testing.
Page:
15
Paragraph:
4
EPA
comment:
Furthermore,
a
number
of
field
and
laboratory
studies
report
reproduction
effects
with
mammals,
suggesting
that
the
possibility
of
endocrine
disruption
effects
on
wild
mammals
should
be
further
examined.
Aventis'
response:
The
statement
should
be
deleted
or
modified.
As
pointed
out
above,
reports
on
reproductive
effects
of
carbaryl
in
the
open
literature
are
at
least
ambivalent.
The
recently
submitted
2
generation
study
in
rats
demonstrated
the
absence
of
reproductive
effects.
If
the
general
statement
about
the
potential
for
endocrine
disruption
of
carbaryl
is
maintained,
references
(or
a
cross
reference
within
the
document)
for
the
above
claim
should
be
provided.
EFED
Response:
As
stated
previously,
chronic
reproductive
tests
have
resulted
in
effects
that
support
EFED's
concerns
regarding
the
endocrine
disrupting
potential
of
carbaryl.
Just
because
one
study
failed
to
show
similar
effects
to
another,
EFED
does
not
believe
that
it
would
be
reasonable
to
discount
the
validity
of
the
earlier
study.
If
anything,
the
data
strongly
suggests
that
additional
data
are
needed
to
better
understand
the
likelihood
of
adverse
effects.
Furthermore,
carbaryl
should
be
subjected
to
tests
specifically
designed
to
address
whether
the
chemical
is
acting
through
endocrinemediated
pathways.
Uncertainties
Page:
15
Paragraph:
Last
Line:
4
EPA
comment:
In
the
absence
of
a
valid
two
generation
rat
reproduction
study,
mammalian
chronic
RQs
were
based
on
a
rat
prenatal
development
study
NOAEC
(MRID#
44732901).
26
Aventis'
response:
A
new
two
generation
study
in
rats
was
recently
submitted.
EFED
Response:
As
mentioned
previously,
the
most
recent
two
generation
reproduction
study
of
rats
was
not
available
for
review
when
the
risk
assessment
was
written;
however,
the
proposed
difference
in
the
NOAEC,
i.
e.,
75
vs
80,
would
not
significantly
impact
the
magnitude
of
the
chronic
mammalian
risk
quotients
nor
would
it
alter
the
fact
that
significant
effects
were
noted
in
the
developmental
study.
However,
the
text
has
been
revised
to
read
"Additionally,
mammalian
chronic
RQs
were
based
on
a
rat
prenatal
development
study
NOAEC
(MRID#
44732901)
rather
than
the
more
traditional
use
of
a
2
generation
reproduction
study."
4.0
Environmental
Fate
Assessment
Exposure
Characterization
Page:
16
Paragraph:
3
Line:
8
EPA
comment:
Environment
(Kf
=1.7
to
3.2).
Aventis'
response:
The
upper
value
Kf
for
carbaryl
should
be
listed
as
3.5
as
referenced
by
EPA
elsewhere
in
the
document
(e.
g.
Table
3,
page
20).
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
test
has
been
revised
to
read
"Kf
=
1.7
to
3.7".
Page:
16
Paragraph:
3
Line:
last
sentence
EPA
comment:
Detailed
discussion
and
reviews
(DERs)
of
the
studies
that
are
included
in
this
assessment
are
attached
in
Appendix
A.
Aventis'
response:
It
is
inappropriate
to
include
the
DERs
in
the
RED.
A
summary
of
study
findings
is
already
included
in
the
EFED
Chapter.
DERs
should
be
made
available
to
the
public
through
the
regular
procedure
under
the
Freedom
of
Information
Act
after
they
have
been
reviewed
and
cleared
for
confidential
business
information.
27
EFED
Response:
EFED
concurs
with
the
registrant's
comments
that
DERs
should
be
made
available
to
the
public
under
the
Freedom
of
Information
Act
after
they
have
been
reviewed
and
cleared
for
confidential
business
information.
Page:
16
Paragraph:
4
Line:
4
EPA
comment:
lower
levels
(generally
less
than
0.01
µ/
L).
Aventis'
response:
value
missing
units
(generally
less
than
0.01
µg/
L).
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
has
revised
the
text
to
read
"0.01
µg/
L".
Page:
16
Paragraph:
5
Line:
4
EPA
comment:
…monitoring
data
is
of
limited
utility
in
developing
EECs
for
ecological
and
human
health
risk
assessment.
Aventis'
response:
The
drinking
water
monitoring
program
conducted
by
the
registrant
provides
a
real
world
assessment
of
the
potential
for
human
exposure
to
carbaryl
in
drinking
water
derived
from
surface
water.
Drinking
water
concentrations
derived
from
PRZM/
EXAMS
greatly
overestimate
the
potential
exposure
to
carbaryl
in
drinking
water,
generally
by
several
orders
of
magnitude.
EFED
Response:
The
limitations
of
the
monitoring
studies
are
discussed
within
the
chapter
and
provide
sufficient
detail
to
support
EFED's
contention
that
"Because
of
the
limited
amount
of
data
available
and
because
of
potential
problems
with
extant
data
.
.
.
monitoring
data
are
of
limited
utility
in
developing
EECs
for
ecological
and
human
health
risk
assessment."
Page:
17
Paragraph:
1
Line:
2
3
EPA
comment:
The
maximum
rate
was
taken
from
the
carbaryl
labels.
Aventis'
response:
It
would
be
of
benefit
for
the
Agency
to
be
explicit
and
list
the
carbaryl
labels
that
were
used
to
develop
the
maximum
application
rates
for
the
model
scenarios.
The
reference
cited
in
the
EFED
Chapter
regarding
the
use
of
carbaryl
on
crops
indicates
that
current
labels
were
not
used
for
the
Agency's
assessment.
Many
of
these
crops
have
been
deleted
from
Aventis'
labels
for
a
few
years
Application
28
rates,
number
of
applications
per
season,
and
PHI's
also
have
changed
for
several
crops
on
the
labels.
EFED
Response:
While
EFED
agrees
that
additional
details
are
of
interest
to
some
readers,
it
isn't
possible
to
address
all
potential
interests
concurrently
and
still
have
a
reasonably
sized
document.
As
noted
in
the
chapter
"Average
and
maximum
reported
rates
were
determined
by
BEAD
[Biological
and
Economic
Assessment
Division]
based
on
data
collected
by
Doane
surveys
and
registrant
market
analysis."
Page:
17
Paragraph:
2
Line:
2
EPA
comment:
For
the
Index
Reservoir
scenario
using
maximum
label
rates,
acute
EEC
values
ranged
from
about
10
µg/
L
from
sugar
beets
to
about
500
µg/
L
from
citrus
(Table
6).
Aventis'
response:
Table
6
on
page
33
shows
a
concentration
of
19
µg/
L
for
sugar
beets
treated
with
the
maximum
label
rate
of
2
x
1.5
lb
ai,
not
10
as
stated
in
this
sentence.
A
low
EEC
value
of
9
µg/
L
for
sugar
beets
results
from
the
"maximum
reported"
application
scenario
of
1
x
1.2
lb
ai/
A.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised
to
read
".
.
.
acute
EEC
values
ranged
from
about
19
:g/
L
from
sugar
beets
to
about
500
:g/
L
.
.
.."
Page:
17
Paragraph:
2
Line:
3
EPA
comment:
Chronic
EECs
ranged
from
about
1
to
28
µg/
L.
Aventis'
response:
Table
6
on
page
33
shows
that
this
is
correct
when
considering
all
of
the
model
scenarios.
However,
either
the
same
maximum
label
rate
reference
should
be
used
as
in
the
preceding
sentence
(in
which
case
the
minimum
chronic
EEC
would
be
2),
or
the
basis
for
the
preceding
sentence
should
be
changed
from
the
maximum
label
rate
to
include
all
application
scenarios
to
keep
the
comparisons
consistent.
29
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised
to
read
"Chronic
EECs
ranged
from
about
2
to
28
:g/
L."
Page:
17
Paragraph:
2
Line:
8
EPA
comment:
The
results
of
the
modeling
provide
an
(sic)
conservative,
though
not
unreasonable,
estimate
on
(sic)
possible
concentrations
[in]
drinking
water.
Aventis'
response:
It
should
be
clear
that
Aventis'
surface
water
monitoring
program
provides
a
more
reasonable
estimate
of
the
potential
drinking
water
exposure
to
carbaryl
than
the
modeling
numbers,
which
overestimate
exposure
by
several
orders
of
magnitude.
EFED
Response:
The
limitations
of
this
study
are
discussed
in
the
chapter.
Page:
17
Paragraph:
2
Line:
last
EPA
comment:
…and
model
input
and
output
files
are
attached
in
appendix
B.
Aventis'
response:
The
PRZM
input
files
for
only
the
Index
Reservoir
drinking
water
modeling
were
provided
as
an
electronic
copy.
The
PRZM
input
files
for
the
standard
pond
scenarios
were
not
provided
in
the
draft
RED
so
Aventis
could
not
assess
the
data.
None
of
the
output
files
were
provided.
EFED
Response:
EFED
concurs
with
the
registrant's
comments;
a
more
comprehensive
set
of
input
files
have
now
been
included
in
the
chapter
(Appendix
F).
Page:
18
Figure
2
EPA
comment:
Figure
1.
Generalized
carbaryl
degradation
pathway
Aventis'
response:
This
should
be
labeled
Figure
2,
not
Figure
1.
30
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
figure
entitled
Generalized
carbaryl
degradation
pathway
has
been
renumbered
Figure
2
Page:
19
Table
3
EPA
comment:
Hydrolysis
half
life
at
pH
9
stated
to
be
5
hours.
Aventis'
response:
The
study
results,
and
the
summary
of
the
study
presented
on
page
20,
show
the
correct
halflife
at
pH
9
to
be
3.2
hours.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
hydrolysis
half
life
reported
for
pH
in
Table
3
has
been
revised
to
read
3.2
hours.
Page:
19
Table
3
EPA
comment:
Aerobic
Aquatic
half
life
4.9.
Aventis'
response:
The
Aerobic
Aquatic
half
life
is
4.9
days
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
aerobic
aquatic
metabolism
half
life
reported
in
Table
3
has
been
revised
to
read
4.9
days.
Page:
19
Table
3
EPA
comment:
Soil
metabolism
T1/
2,
anaerobic,
assumed
stable
31
Aventis'
response:
If
this
guideline
is
satisfied
by
the
data
submitted
for
guideline
162
3,
it
is
not
clear
why
the
compound
is
assumed
to
be
stable
rather
than
having
a
half
life
in
line
with
the
72
days
that
resulted
from
the
anaerobic
aquatic
study.
Although
this
parameter
plays
a
fairly
insignificant
role
in
estimating
the
amount
of
carbaryl
available
for
runoff
in
the
models,
it
could
play
a
significant
role
if
one
were
to
use
this
value
in
estimating
leaching
potential
in
subsurface
horizons.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
anaerobic
soil
metabolism
half
life
reported
in
Table
3
has
been
revised
to
read
72
days.
This
does
not
significantly
change
the
model
results.
Page:
20
Table
3
EPA
comment:
Batch
Equilibrium
1/
n
values
ranged
from
0.86
1.02
Aventis'
response:
These
values
are
for
the
desorption
isotherms
only.
For
the
adsorption
isotherms
that
were
used
to
calculate
the
adsorption
Kf
and
Koc
values
listed
in
the
table,
the
correct
range
of
1/
n
values
are
0.78
to
0.84
as
stated
on
page
22.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
batch
equilibrium
1/
n
value
range
reported
in
Table
3
has
been
revised
to
read
0.78
to
0.84.
Page:
20
Table
3
EPA
comment:
Foliar
Dissipation
30
days
Willis
and
McDowell,
1987
Aventis'
response:
The
foliar
dissipation
half
life
listed
by
EFED
is
incorrect.
Table
IV
of
the
Willis
and
McDowell
review
lists
10
foliar
half
lives
for
various
formulations
of
carbaryl
applied
to
different
crops.
Five
of
these
half
lives
are
for
a
study
designed
to
evaluate
a
new
analytical
procedure
for
measuring
carbaryl
residues
on
plants.
This
study
was
conducted
on
plants
grown
in
a
greenhouse,
with
some
of
them
receiving
an
unknown
amount
of
simulated
rainfall.
These
studies
on
greenhouse
grown
plants
should
not
be
used
to
evaluate
foliar
persistence
in
the
field.
The
foliar
persistence
of
pesticides
can
be
considerably
different
for
residues
on
and
in
plants
grown
in
greenhouses
versus
the
field.
Eliminating
the
half
lives
for
the
greenhouse
grown
plants
results
in
the
following
half
lives
for
carbaryl
on
field
32
plants:
Cotton,
1.2,
1.3,
1.5
days;
strawberry,
4.1
days;
tomato
1.4
days.
Therefore,
the
longest
half
life
of
4.1
days
should
be
listed
in
this
table.
Aventis
intends
to
conduct
a
more
thorough
review
of
the
data
on
the
foliar
dissipation
of
carbaryl
and
prepare
a
more
detailed
response
during
the
60
day
public
comment
period.
EFED
Response:
EFED
has
reviewed
the
Willis
paper
and
agrees
that
the
foliar
dissipation
rate
for
carbaryl
is
not
well
known
and
may
be
significantly
shorter
then
the
default
value
used.
However,
as
defined
in
EFED
policy,
the
default
value
is
used
when
scientifically
valid,
statistically
robust
data
are
not
available
to
make
a
more
accurate
estimation.
EFED
encourages
development
of
better
data
to
justify
using
a
different
value.
Persistence
Microbially
Mediated
Processes
Page:
21
Paragraph:
3
Line:
3
EPA
comment:
with
an
initial
concentration
of
11.2
mg/
L,
degraded
with
a
half
life
of
4.0
days
in
sandy
Aventis'
response:
The
units
for
ppm
soil
concentration
should
be
given
as
mg/
kg.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised
to
read
"11.2
mg/
kg".
Page:
21
Paragraph:
3
Line:
4
5
EPA
comment:
The
major
degradate
was
1
naphthol
which
further
degraded
rapidly
to
non
detectable
levels
within
14
days.
Aventis'
response:
The
data
from
this
study
demonstrate
that
under
aerobic
soil
conditions
the
formation
and
decline
of
1
naphthol,
starting
from
parent
carbaryl
is
complete
in
less
than
14
days.
The
study
data
show
an
average
maximum
1
naphthol
level
of
34.5%
of
applied
carbaryl
by
day
1,
declining
to
2.8%
by
day
2,
0%
by
day
4,
0.2%
by
day
7
and
0%
at
day
14.
These
data
suggest
a
preliminary
half
life
of
less
than
1
day
for
the
major
degradate
1
naphthol.
33
EFED
Response:
EFED
agrees
that
the
pattern
of
formation
and
decline
suggests
that
1
naphthol
degrades
rapidly.
However,
from
the
data
it
is
not
possible
to
calculate
a
valid
half
life
for
1
naphthol
degradation.
There
are
too
many
processes
(formation
and
degradation,
sorption
and
desorption
for
example)
to
permit
solving
the
multiple
differential
equations
for
the
different
rate
constants.
Page:
21
Paragraph:
3
Line:
8
9
EPA
comment:
In
anaerobic
aquatic
soil
carbaryl
with
an
about
10
mg/
L
degraded
with
a
half
life
of
72.2
days.
Aventis'
response:
Several
words
appear
to
be
missing
from
this
sentence.
One
suggestion:
"Carbaryl
degraded
with
a
half
life
of
72.2
days
in
anaerobic
aquatic
sediment
with
an
initial
carbaryl
concentration
of
about
10
mg/
L."
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised
to
read
"Carbaryl
degraded
with
a
half
life
of
72.2
days
in
anaerobic
aquatic
sediment
with
an
initial
carbaryl
concentration
of
about
10
mg/
L;
1
naphthol
was
the
major
degradate."
Page:
22
Paragraph
carried
over
from
page
21
Line:
4
on
pg
22
EPA
comment:
Chudhry
and
Wheeler,
1988
Aventis'
response:
This
reference
is
not
included
in
the
reference
list
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised
to
read
"Chaudhry
et
al.,
1988.
The
references
section
has
been
revised
to
include
"Chaudhry,
G.
R.,
A.
N.
Ali,
and
W.
B.
Wheeler,
1988.
Isolation
of
a
methyl
parathion_
degrading
Pseudomonas
sp.
that
possesses
DNA
homologous
to
the
opd
gene
from
a
Flavobacterium
sp.
Appl.
Environ.
Microbiol.,
54:
288_
293.
Mobility
Page:
22
Paragraph:
1
Line:
1
EPA
comment:
Carbaryl
is
considered
to
be
mobile
to
very
mobile
in
soils.
34
Aventis'
response:
See
response
directly
below.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised
to
read
"Carbaryl
is
considered
to
be
moderately
mobile
in
soils."
Page:
22
Paragraph:
3
Line:
1
2
EPA
comment:
Based
on
batch
equilibrium
experiments
(MRID
43259301)
carbaryl
was
determined
to
be
very
mobile
to
mobile
in
soils.
Aventis'
response:
The
classification
of
carbaryl
as
mobile
to
very
mobile
is
inconsistent
with
measured
Koc
values
of
177
to
249.
According
to
the
widely
used
classification
scheme
of
McCall,
et
al.
(1980)
wherein
Koc
values
between
150
and
500
denote
medium
mobility
in
soil,
carbaryl
would
be
classified
as
having
medium
mobility
in
most
soils.
This
classification
of
medium
mobility
is
further
supported
by
the
acceptable
column
leaching
study
(MRID
43320701)
in
which
aged
carbaryl
residues
were
only
slightly
mobile
in
a
number
of
soils.
The
mobility
of
carbaryl
would
be
expected
to
be
higher
in
sandy
soils
or
in
soils
of
low
organic
matter.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised
to
read
"Based
on
batch
equilibrium
experiments
(MRID
43259301)
carbaryl
was
determined
to
be
moderately
mobile
to
mobile
in
soils."
Field
Dissipation
Page:
22
Paragraph:
5
Line:
3
EPA
comment:
The
submitted
field
and
aquatic
dissipation
studies
were
determined
to
be
unacceptable,
and
did
not
provide
useful
information
on
movement
and
dissipation
of
carbaryl
or
its
degradation
products.
Aventis'
response:
The
field
dissipation
study
(MRID
41982605)
submitted
in
1991
demonstrated
that
carbaryl
dissipated
very
rapidly
(t1/
2
<
1
week)
with
no
measurable
leaching.
The
study
included
two
sites,
one
in
North
Carolina
and
one
in
California.
At
the
North
Carolina
site,
~
95%
of
the
Time
0
residues
had
dissipated
by
the
first
sampling
period
7
days
after
application
(the
planned
first
sampling
at
3
days
was
not
collected
due
to
rain).
Similarly,
~
85%
of
the
Time
0
residues
had
dissipated
by
7
days
after
application
at
the
California
site.
Concerning
the
35
movement
of
carbaryl,
samples
were
taken
to
a
depth
of
0.9
meters
in
increments
of
0.15
meters.
No
residues
were
found
below
the
upper
0.15
meters.
EFED
Response:
This
field
dissipation
study
(MRID
41982605)
was
reviewed
and
determined
to
be
scientifically
invalid.
As
described
in
the
text,
these
studies
do
not
provide
reliable
information
on
the
rate
of
dissipation
of
parent
carbaryl
or
formation
of
degradation
products
because
of
inappropriate
sampling
intervals,
poor
sample
storage
stability,
lack
of
degradate
monitoring,
rainfall
and
irrigation
that
were
less
than
evapotranspiration,
and
irrigation
water
with
high
pH.
The
registrant
is
required
to
conduct
additional
studies
and
submit
new
data.
When
the
studies
have
been
reviewed
and
determined
to
be
acceptable,
the
data
will
be
incorporated
into
future
assessments.
Page:
23
Paragraph:
3
Line:
2
EPA
comment:
Because
of
inappropriate
sampling
intervals,
poor
sample
storage
stability,
lack
of
degradate
monitoring,
rainfall
and
irrigation
that
were
less
than
evapotranspiration,
and
irrigation
water
with
high
pH,
these
studies
do
not
provide
reliable
information
on
the
rate
of
dissipation
of
parent
carbaryl
or
formation
of
degradation
products.
Aventis'
response:
The
estimated
half
life
determined
from
this
study
was
<
3
days.
Sampling
at
intervals
such
that
several
sampling
events
are
taken
prior
to
the
half
life
of
the
product
is
impractical
for
rapidly
degrading
chemicals
(e.
g.,
those
with
half
lives
less
than
a
week).
For
this
rapidly
degrading
chemical
an
estimate
of
the
half
life
should
be
sufficient
for
risk
assessments
even
if
it
is
not
precise.
After
the
report
was
submitted
to
California,
the
freezer
storage
stability
recoveries
at
six
and
nine
months
were
measured
but
not
reported.
Rainfall
plus
irrigation
approximated
an
inch
a
week
and
was
more
than
enough
to
maintain
a
good
soil
moisture
for
agricultural
purposes.
Sulfuric
acid
is
routinely
added
to
irrigation
water
in
the
region
of
California
where
the
field
test
was
conducted
to
neutralize
the
water's
high
pH.
Although
not
stated
in
the
report,
the
irrigation
water
in
the
California
trial
was
treated
in
the
typical
commercial
fashion.
The
acid
is
injected
into
the
irrigation
pipe
as
water
is
pumped
through
it.
Unfortunately,
the
pH
of
the
water
arriving
at
the
field
after
treatment
was
not
measured.
EFED
Response:
As
discussed
in
the
preceding
response,
the
terrestrial
field
dissipation
study
was
reviewed
and
determined
to
be
scientifically
invalid.
The
registrant
is
required
to
conduct
additional
studies
and
submit
new
data.
When
the
studies
have
been
completed
and
reviewed
and
determined
to
be
acceptable
the
data
will
be
incorporated
into
future
assessments.
36
Aquatic
Field
Dissipation
Page:
24
Paragraph:
2
Line:
3
EPA
comment:
They
(do)
not
provide
useable
information
on
the
dissipation
of
carbaryl
and
1
naphthol
in
aquatic
field
conditions.
Aventis'
response:
The
soil
metabolism
study
referred
to
in
the
report
found
that
the
total
water
soluble
metabolites
did
not
exceed
5%
of
the
total
radioactive
residue,
the
primary
hydrolysis
product,
1
naphthol,
was
not
found,
and
that
the
only
analyte
of
concern
was
the
parent
insecticide,
carbaryl.
A
soil
metabolism
study
reviewed
concurrently
by
the
Agency
was
issued
later
(MRID
42785101,
classified
"acceptable")
with
similar
results.
Although
the
major
soil
metabolite,
1
naphthol,
was
found
at
significant
levels
at
day
0
and
day
1,
the
levels
were
less
than
0.7%
by
day
4
and
non
detectable
by
day
14.
Two
other
metabolites
were
identified
but
never
exceeded
levels
of
1.7%
of
the
total
residue.
Again
the
only
residue
of
concern
was
the
parent
insecticide,
carbaryl.
If
present,
1
naphthol
would
have
been
detected
by
the
residue
method
used
to
measure
the
residues
of
carbaryl
in
the
soil.
The
estimated
half
life
determined
from
this
study
was
<
2
days.
Sampling
at
intervals
such
that
several
sampling
events
are
taken
prior
to
the
half
life
of
the
product
is
impractical
for
rapidly
degrading
chemicals
(e.
g.
those
with
half
lives
less
than
a
week).
EFED
Response:
The
aquatic
field
dissipation
study
was
reviewed
and
determined
to
be
unacceptable
since
it
did
not
provide
useable
information
on
the
dissipation
of
carbaryl
and
1
naphthol
under
aquatic
field
conditions.
The
registrant
is
encouraged
to
conduct
additional
studies
and
submit
new
data.
In
future
studies
sampling
intervals
should
be
selected
that
are
appropriate
for
the
expected
half
life.
When
the
studies
have
been
reviewed
and
determined
to
be
acceptable
the
data
will
be
incorporated
into
future
assessments.
37
Page:
24
Paragraph:
2
Line:
4
EPA
comment:
Frozen
storage
stability
data
were
provided
for
only
6
months,
although
the
water
samples
were
stored
for
up
to
14
months
and
the
soil
samples
were
stored
for
up
to
17.5
months
prior
to
analysis.
The
data
suggest
that
carbaryl
and
1
naphthol
degraded
significantly
during
storage.
In
the
six
months
of
storage
carbaryl
degraded
an
average
of
34
%
in
Texas
water
and
39%
in
from
Mississippi.
1
naphthol
degraded
50%
in
water
from
Texas
and
69%
from
Mississippi.
Degradation
did
not
appear
linear,
and
it
is
not
possible
to
extrapolate
out
to
14
months.
It
was
therefore
not
possible
to
evaluate
the
actual
concentrations
of
carbaryl
and
1
naphthol
in
the
samples
or
estimate
the
dissipation
rates.
Aventis'
response:
The
existing
6
month
storage
stability
provides
sufficient
information
to
calculate
the
concentrations
of
carbaryl
in
the
samples.
However,
the
metabolite
1
naphthol
was
shown
to
degrade
significantly
under
the
same
freezer
conditions.
This
instability
simply
confirms
that
1
naphthol's
presence
in
the
environment
would
be
very
limited
and
should
not
be
of
concern.
EFED
Response:
As
discussed
in
the
preceding
response,
the
aquatic
field
dissipation
study
was
classified
as
unacceptable.
Degradation
did
not
appear
to
be
linear,
and
it
is
not
possible
to
extrapolate
out
to
14
months;
therefore
it
is
not
possible
to
evaluated
the
actual
concentrations
of
carbaryl
and
1
naphthol
in
the
samples
or
estimate
the
dissipation
rates.
Foliar
Dissipation
Page:
24
Paragraph:
Last
EPA
comment:
The
reported
rates
of
carbaryl
dissipation
from
foliar
surfaces
varies
from
1
days
to
30
days.
In
their
review
of
literature
data
on
pesticide
foliar
persistence,
Willis
and
McDowell
(1987)
report
that
carbaryl
dissipation
rates
varied
from
1.2
to
29.5
days…
For
terrestrial
risk
assessment
modeling
EFED
used
35
days…
Aventis'
response:
As
stated
in
comments
to
Table
3,
the
foliar
dissipation
half
life
used
by
EFED
for
terrestrial
risk
assessment
is
too
long
and
should
be
corrected.
Table
IV
of
the
Willis
and
McDowell
review
lists
10
foliar
half
lives
for
various
formulations
of
carbaryl
applied
to
different
crops.
Five
of
these
half
lives
are
for
a
study
designed
to
evaluate
a
new
analytical
procedure
for
measuring
carbaryl
residues
on
plants.
This
study
was
conducted
on
plants
grown
in
a
greenhouse,
with
some
of
them
receiving
an
unknown
amount
of
simulated
rainfall.
These
studies
on
greenhouse
grown
plants
should
not
be
used
to
evaluate
foliar
persistence
in
the
field.
The
foliar
persistence
of
pesticides
can
be
considerably
different
for
38
residues
on
and
in
plants
grown
in
greenhouses
versus
the
field.
Eliminating
the
half
lives
for
the
greenhouse
grown
plants
results
in
the
following
half
lives
for
carbaryl
on
field
plants:
Cotton,
1.2,
1.3,
1.5
days;
strawberry,
4.1
days;
tomato
1.4
days.
Therefore,
the
longest
half
life
of
4.1
days
should
be
used
for
terrestrial
risk
assessment
modeling.
Aventis
will
conduct
a
more
thorough
review
of
the
data
on
the
foliar
dissipation
of
carbaryl
and
prepare
a
more
detailed
response
during
the
60
day
public
comment
period.
EFED
Response:
EFED
agrees
that
the
dissipation
of
carbaryl
on
foliar
surfaces
is
not
well
understood.
The
registrant
is
encouraged
to
submit
additional
data
on
foliar
dissipation
to
help
clarify
the
rate
and
processes
involved.
Until
scientifically
valid,
statistically
robust
data
are
submitted,
EFED
policy
is
to
use
a
default
value
of
35
days
and
assume
first
order
degradation
kinetics.
Atmospheric
Transport
Page:
25
Paragraph:
1
Line:
2
EPA
comment:
Waite,
et
al.,
1995
Aventis'
response:
This
reference
is
not
included
in
the
reference
list
EFED
Response:
EFED
concurs
with
the
registrant's
comments.
The
reference
section
has
been
revised
to
include
the
following
reference:
Waite,
D.
T.,
R.
Grover,
N.
D.
Westcott,
D.
G.
Irvine,
L.
A.
Kerr
and
H.
Sommerstad,
1995.
Atmospheric
Deposition
of
Pesticides
in
a
Small
Southern
Saskatchewan
Watershed.
Environ.
Toxicol.
and
Chem.,
14:
1171
1175.
Page:
25
Paragraph:
1
Line:
3
EPA
comment:
Beyer
et
al.,
(1995)
Aventis'
response:
This
reference
is
not
included
in
the
reference
list
EFED
Response:
EFED
concurs
with
the
registrant's
comments.
The
reference
section
has
been
revised
to
include
the
following
reference:
Beyer,
D.
W.,
M.
S.
Farmer
and
P.
J.
Sikoski,
1995.
Effects
of
rangeland
aerial
application
on
Sevin
4
Oil
®
on
fish
and
aquatic
invertebrate
drift
in
the
Little
Missouri
River,
North
Dakota.
Arch.
Environ.
Contam.
Toxicol.,
28:
27
34.
39
Page:
25
Paragraph:
3
Line:
5
EPA
comment:
Schomburg
et
al.
(1991)
Aventis'
response:
This
reference
is
not
included
in
the
reference
list
EFED
Response:
EFED
concurs
with
the
registrant's
comments.
The
reference
section
has
been
revised
to
include
the
following
reference:
Schomburg,
C.
J.,
D.
E.
Glotfelty,
and
J.
N.
Seiber,
1991.
Pesticide
occurrence
and
distribution
in
fog
collected
near
Monetery
California.
Environ.
Sci.
Technol.
25:
155
160.
1
Naphthol
Fate
and
Transport
Page:
26
Paragraph:
2
Line:
1
2
EPA
comment:
In
an
aerobic
soil
metabolism
study
(MRID
42785101),
1
naphthol
degraded
rapidly
to
nondetectable
levels
within
14
days.
Aventis'
response:
The
data
from
this
study
demonstrate
that
under
aerobic
soil
conditions
the
formation
and
decline
of
1
naphthol,
starting
from
parent
carbaryl,
is
complete
in
less
than
14
days.
The
study
data
show
an
average
maximum
1
naphthol
level
of
34.5%
of
applied
carbaryl
by
day
1,
declining
to
2.8%
by
day
2,
0%
by
day
4,
0.2%
by
day
7
and
0%
at
day
14.
These
data
suggest
a
preliminary
half
life
of
less
than
1
day
for
the
major
degradate
1
naphthol.
This
half
life
can
be
used
for
preliminary
environmental
fate
modeling
to
estimate
EECs
for
1
naphthol.
EFED
Response:
As
stated
previously,
it
is
not
possible
to
separate
the
multiple
processes
occurring
in
this
study,
and
it
is
not
possible
to
calculate
rate
constant
for
degradation
of
1
naphthol.
Additional
data
on
the
degradation
of
1
naphthol
are
required.
40
Page:
26
Paragraph:
3
Line:
1
EPA
comment:
No
guideline
information
was
submitted
on
1
naphthol
sorption.
Literature
information
suggests
that
it
is
not
strongly
sorbed.
Aventis'
response:
The
statement
suggesting
that
1
naphthol
is
not
strongly
sorbed
to
soil
should
be
deleted.
In
support
of
the
1
naphthol
sorption
statement
the
Agency
has
cited
only
one
paper
by
Karthikeyan
et
al.
(1999)
that
was
conducted
using
aluminum
hydroxide
as
the
sorbent.
Soil
is
composed
of
much
more
than
aluminum
hydroxide,
so
this
study
is
more
of
a
mechanistic
description
of
sorption
to
this
one
component
of
soil
and
not
a
study
of
sorption
to
soil
as
a
whole.
This
cited
study
reported
that
1
naphthol
does
not
show
significant
sorption
to
aluminum
hydroxide
when
allowed
to
sorb
for
20
hours
in
the
dark
in
the
absence
of
oxygen.
However,
there
was
a
significant
increase
in
sorption
with
increasing
equilibration
time,
and
as
the
Agency
stated,
the
increase
is
influenced
by
pH,
as
would
be
expected
for
an
acidic
phenolic
compound.
Additional
information
available
in
the
literature
demonstrates
that
the
sorption
of
1
naphthol
to
soil
is
stronger
than
that
seen
for
carbaryl
itself.
Hassett
et
al.
(1981)
have
demonstrated
that
the
sorption
of
1
naphthol
was
the
result
of
sorption
to
organic
carbon
resulting
in
an
average
Koc
of
431
±
40
for
10
of
the
16
soil
samples
they
tested.
In
the
remaining
6
soil
samples
the
Koc
was
even
higher
(1,645
to
15,618).
Hassett
et
al.
(reference
submitted
as
part
of
30
day
response
document)
hypothesized
that
the
higher
Kocs
in
these
6
soils,
in
which
the
organic
carbon
to
clay
ratio
was
very
low,
the
clay
surfaces
were
more
accessible
and
the
sorption
of
1
naphthol
was
apparently
controlled
by
the
clay
fraction.
In
Burgos
et
al.
(1999),
cited
by
EPA
elsewhere
in
the
RED,
it
was
shown
that
there
is
significant
sorption
of
1
naphthol
to
two
sandy
soils,
and
that
oxidative
coupling
reactions
were
responsible
for
the
strongly
bound
portion.
In
an
earlier
paper
by
Burgos
et
al.
(1996)
it
was
shown
that
both
biologically
mediated
and
soil
catalyzed
oxidative
coupling
lead
to
significant
binding
of
1
naphthol
residues
to
soil.
These
data
indicate
that
1
naphthol
is
less
mobile
and
less
susceptible
to
leaching
than
carbaryl
itself,
and
they
demonstrate
that
at
least
a
portion
of
the
1
naphthol
residue
is
tightly
sorbed
to
soil
constituents.
To
meet
the
requirement
by
the
Agency
for
information
on
the
adsorption
and
desorption
of
1
naphthol,
the
registrant
is
conducting
an
adsorption/
desorption
study
to
meet
the
163
1
guideline.
Study
results
should
be
available
for
submission
to
the
Agency
in
the
first
quarter
of
the
calendar
year
2002.
EFED
Response:
Data
from
the
Hassett
paper
have
been
included.
The
text
reads
"Hassett
et
al.
(1981)
reported
an
average
1
naphthol
Koc
of
431
(±
40)
for
10
of
the
16
soils
tested.
They
also
found
that
in
other
soils
with
very
low
organic
carbon
to
clay
ratios
clay
surfaces
controlled
sorption.
Additional
data
on
41
1
naphthol
sorption
is
required
to
fully
characterize
mobility."
Additional
data
will
be
reviewed
and
incorporated
into
future
risk
assessments.
Aquatic
Exposure
Assessment
Surface
Water
Page:
26
Paragraph
4
Line
1
EPA
comment:
Five
crop
scenarios:
apples,
field
corn,
sweet
corn,
oranges
and
sweet
potatoes
scenarios
were
use
in
modeling
for
surface
water
EEC.
Aventis'
response:
The
fifth
crop
modeled
was
sugar
beets
(not
sweet
potatoes).
EFED
Response:
EFED
concurs
with
the
registrant's
comments.
The
text
has
been
revised
to
read
"Five
crop
scenarios:
apples,
field
corn,
sweet
corn,
oranges
and
sugar
beets
scenarios
were
used
in
modeling
for
surface
water
EEC."
Page:
27
Table
4
EPA
comment:
Hydrolysis
half
life
at
pH
9
stated
to
be
5
hours.
Aventis'
response:
The
study
results,
and
the
summary
of
the
study
presented
on
page
20,
show
the
correct
halflife
at
pH
9
to
be
3.2
hours.
EFED
Response:
EFED
concurs
with
the
registrant's
comments.
The
hydrolysis
half
life
at
pH
9
reported
in
Table
4
has
been
revised
to
read
"3.2
hours".
Page:
27
Table
4
EPA
comment:
(Koc
=
211
for
SCIGROW)
Aventis'
response:
This
is
the
mean
Koc.
According
to
EPA
guidance
the
median
Koc
(209)
should
be
used
for
SCI
GROW,
although
this
difference
would
not
be
expected
to
affect
the
model
results.
42
EFED
Response:
EFED
concurs
with
the
registrant's
comments.
The
mean
soil
partitioning
coefficient
(Koc)
reported
in
Table
4
now
reads
"(
Koc
=
209
for
SCIGROW)".
Pages:
27
28
Table
5
EPA
comment:
Tier
II
surface
water
estimated
environmental
concentration
(EEC)
values
derived
from
PRZM/
EXAMS
modeling
for
use
in
ecorisk
assessment
(calculated
using
standard
pond.)
Aventis'
response:
The
PRZM
input
tables
were
not
provided
for
the
standard
pond
scenarios,
so
the
assumption
is
made
that
the
same
application
methods
were
used
for
the
standard
pond
as
for
the
Index
Reservoir
scenarios
that
were
provided
as
an
electronic
copy
of
a
draft
of
Appendix
B.
EFED
Response:
The
registrant's
assumption
is
correct,
i.
e.,
the
same
application
methods
were
used
for
the
standard
pond
as
for
the
Index
Reservoir
scenarios.
Aventis'
comment:
It
would
be
of
benefit
for
the
Agency
to
state
which
of
the
carbaryl
labels
were
used
to
develop
the
"maximum"
label
application
rate
scenarios.
It
would
be
useful
to
add
another
column
to
this
table
to
specify
which
method
of
application
was
used
to
generate
the
EECs
rather
than
the
generic
"air/
ground"
in
column
1.
There
are
a
number
of
errors
in
the
input
parameters
(noted
below)
that
would
lead
to
changes
in
the
calculated
EECs
and
therefore
the
risk
quotients
for
these
uses.
EFED
Response:
EFED
has
reviewed
the
application
rates
used
in
modeling.
The
changes
suggested
by
the
registrant
do
not
result
in
significant
changes
in
the
risk
assessment;
therefore,
the
modeling
was
not
redone.
As
with
most
chemicals,
the
labels
are
in
a
constant
state
of
flux.
Uses
are
dropped
and
rates
varied
constantly.
Also
this
chemical
has
a
large
number
of
labels
making
it
difficult
for
EFED
to
monitor
the
changing
"current"
labels.
The
use
of
average
use
rates
was
to
allow
evaluation
of
EECs
based
on
rates
other
then
the
maximum
allowed.
The
data
that
were
used
to
calculate
"average"
are
not
highly
robust.
It
is
also
not
always
possible
to
use
the
values
in
the
Quantitative
Use
Assessment
(QUA)
as
presented.
For
example
the
average
number
of
applications
for
sugar
beets
was
1.1
per
year.
EFED
selected
rates
and
timing
to
try
to
capture
the
information
in
the
QUA
table.
The
values
should
nor
be
considered
hard,
exact
numbers.
43
If
the
modeling
for
the
"average"
scenarios
were
conducted
using
aerial
applications
for
citrus
and
apples
(as
was
the
case
for
the
Index
Reservoir
scenarios),
then
the
model
results
over
estimate
the
contributions
from
spray
drift.
Few
applications
to
these
crops
are
made
aerially.
Therefore,
the
model
results
over
estimate
the
contributions
from
spray
drift
since
the
"average"
applications
to
these
crops
are
made
using
ground
airblast
equipment
with
a
spray
drift
of
6.3%
in
the
model
versus
aerial
applications
with
a
spray
drift
of
16%.
The
"average"
scenario
for
sweet
corn
in
Ohio
should
be
3
applications
at
1.1
lb.
ai/
A/
application
(as
noted
in
the
memo,
"Average
application
rate
from
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD")
and
not
the
2
applications
at
3.4
lb.
ai/
A/
application
as
listed
in
the
table.
It
should
be
noted
that
the
"average"
scenario
presented
in
this
table,
2
applications
per
year
at
3.4
lb.
ai
per
application,
exceed
the
maximum
rate
allowed
on
the
label.
The
maximum
label
rate
application
scenario
for
apples
that
is
allowed
by
the
Sevin
brand
XLR
PLUS
label
(E.
P.
A.
Reg.
No
264
333),
the
Sevin
brand
80WSP
and
CHIPCO
Sevin
brand
80WSP
labels
(E.
P.
A.
Reg.
No
264
526)
and
the
CHIPCO
Sevin
brand
SL
label
(E.
P.
A.
Reg.
No
264
335)
is
5
applications
at
3
lb.
ai/
A/
application
made
every
14
days.
The
scenario
used
in
the
model
applies
less
than
the
maximum
amount
of
product
allowed
by
the
labels.
In
addition,
if
the
same
application
timing
was
used
in
the
modeling
for
the
standard
pond
scenario
as
was
used
in
the
index
reservoir
scenario
(applications
made
by
air
every
4
days)
this
would
be
a
violation
of
the
Aventis
labels
which
restrict
applications
to
a
minimum
of
every
14
days.
The
"average"
scenario
for
sugar
beets
in
Minnesota
should
be
1
application
at
1.3
lb.
ai/
A/
application
(as
noted
in
the
memo,
"Average
application
rate
from
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD")
and
not
1
application
at
1.5
lb.
ai/
A/
application
as
listed
in
the
table.
EFED
Response:
The
Quantitative
Use
Assessment
lists
the
"average"
lb
A.
I./
acre
at
1.5
and
the
average
number
of
applications
as
1.1.
The
"Citrus"
scenario
would
be
more
appropriately
labeled
Oranges.
For
the
average
scenario,
the
3.4
lb.
ai/
A/
application
rate
listed
in
Table
5
is
for
oranges
(as
noted
in
the
memo,
"Average
application
rate
from
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD"),
which
is
the
highest
"average"
application
rate
for
any
type
of
citrus.
Therefore,
this
"average"
scenario
for
oranges
are
at
the
high
end
for
all
citrus
and
overestimates
the
PRZM/
EXAMS
derived
EECs
for
use
in
the
other
citrus
crops.
"Average"
application
rates
for
other
citrus
as
listed
in
the
memo
are:
44
Lemons
–
1.3
applications
at
2.7
lb
ai/
A/
appl
Grapefruit
–
1.6
applications
at
1.4
lb
ai/
A/
appl
Citrus,
other
–
1.8
applications
at
1.8
lb
ai/
A/
appl
The
maximum
label
application
rate
for
citrus
is
7.5
lb
ai
per
application,
not
5
lb
ai,
with
a
maximum
of
20
lb
ai
total
allowed
per
year.
In
California
only,
a
single
application
is
allowed
at
the
rate
of
5
to
16
lb
ai
per
season
for
control
of
California
red
scale
and
yellow
scale.
EFED
Response:
Table
5
has
been
revised
to
read
"oranges"
instead
of
"citrus".
Estimated
Environmental
Concentrations
for
Terrestrial
Ecological
Risk
Assessment
Page:
29
Paragraph:
2
Line:
2
4
EPA
comment:
In
the
absence
of
reliable
foliar
dissipation
data
a
dissipation
half
life
of
35
days
is
used.
Published
literature
shows
that
carbaryl
dissipation
rates
vary,
and
are
among
the
highest
observed
for
any
pesticide
(Willis
and
McDowell,
1987).
Aventis'
response:
As
stated
in
more
detail
above,
some
of
the
foliar
dissipation
half
lives
listed
in
this
reference
are
high
because
they
were
generated
in
the
greenhouse,
not
in
the
field,
and
therefore
they
should
not
be
used.
Eliminating
the
half
lives
for
the
greenhouse
grown
plants
results
in
the
following
half
lives
for
carbaryl
on
field
plants:
Cotton,
1.2,
1.3,
1.5
days;
strawberry,
4.1
days;
tomato
1.4
days.
Therefore,
the
longest
half
life
of
4.1
days
should
be
used
for
terrestrial
risk
assessment
modeling.
EFED
Response:
As
in
the
response
provided
above,
EFED
agrees
that
the
dissipation
of
carbaryl
on
foliar
surfaces
is
not
well
known.
Until
additional
data
are
provided
the
default
value
is
used.
Page:
29
Paragraph:
2
Line:
6
EPA
comment:
A
more
thorough
description
of
the
model
calculations
and
ELL
FATE
outputs
are
attached
in
Appendix
B.
Aventis'
response:
No
such
description
or
attachments
were
provided,
so
Aventis
did
not
have
the
opportunity
to
evaluate
the
model.
45
EFED
Response:
EFED
concurs
with
the
registrant's
comments.
A
more
thorough
description
of
the
ELL
FATE
model
along
with
copies
of
its
input
and
output
files
are
contained
in
Appendix
E.
Page:
29
Paragraph:
2
Line:
last
EPA
comment:
…Tables
4,7,
8
and
9,
Appendix
D.
Aventis'
response:
These
tables
are
in
Appendix
C.
EFED
Response:
EFED
concurs
with
the
registrant's
comments.
The
text
has
been
revised
to
read
"EEC
values
calculated
for
different
crop
applications
are
presented
in
Tables
4,
7,
8,
and
9,
Appendix
C."
5.0
Drinking
Water
Assessment
Water
Resources
Assessment
Page:
29
Paragraph:
3
Line:
3
EPA
comment:
Carbaryl
tends
not
to
partition
to
soil,
aquifer
solids,
or
sediment.
Aventis'
response:
This
sentence
is
misleading
and
should
be
reworded.
Carbaryl
does
partition
onto
these
sorbents,
but
the
sorption
coefficients
are
not
high.
Suggest
rewording
this
such
as:
"Carbaryl
tends
not
to
bind
tightly
to
soil,
aquifer
solids,
or
sediment."
EFED
Response:
EFED
concurs
with
the
registrant's
comments.
The
text
has
been
revised
to
read
"Carbaryl
tends
not
to
bind
tightly
to
soil,
aquifer
solids,
or
sediment."
Page:
29
Paragraph:
4
EPA
comment:
Under
certain
conditions
carbaryl
can
be
expected
to
persist
in
the
environment.
Under
low
pH
conditions
the
compound
is
stable
to
hydrolysis.
In
anaerobic
environments
metabolism
is
fairly
slow
(t½
=
72
days).
This
suggests
that
carbaryl
may
leach
to
ground
water
and
persist
in
some
aquifers.
46
Aventis'
response:
This
last
statement
should
be
removed.
In
contrast
to
this
hypothesis
are
the
data
presented
in
the
NAWQA
and
EPA
databases
that
demonstrate
that
carbaryl
is
not
likely
to
leach
to
ground
water
and
is
not
likely
to
persist
in
aquifers.
The
fact
that
carbaryl
has
been
widely
used
in
agricultural
and
urban
settings
for
more
than
35
years,
and
yet
is
found
at
concentrations
greater
than
0.1
µg
/L
in
only
0.027%
of
the
agricultural
wells,
urban
wells
and
aquifers
sampled
by
NAWQA
(Kolpin,
2001),
indicates
that
this
statement
has
little
merit.
Furthermore,
the
last
sentence
is
in
direct
contradiction
to
the
statement
made
at
the
beginning
of
the
preceding
paragraph
that
carbaryl
"…
has
limited
potential
to
leach
to
ground
water."
EFED
Response:
EFED
concurs
with
the
registrant's
comments.
The
last
sentence
of
the
paragraph
has
been
deleted
and
the
text
reads
"Under
certain
limited
conditions
carbaryl
may
be
expected
to
persist
in
the
environment.
Under
low
pH
conditions
the
compound
is
stable
to
hydrolysis.
In
anaerobic
environments
metabolism
is
fairly
slow
(t½
=
72
days)."
Page:
30
Paragraph:
1
Lines
1
3
EPA
comment:
Surface
water
monitoring
studies
show
that
carbaryl
is
the
second
most
widely
detected
insecticide
after
diazinon.
Carbaryl,
at
typically
low
concentrations,
is
found
in
greater
than
20
%
of
surface
samples
at
concentrations
up
to
7
ppb.
Aventis'
response:
These
summary
statements
are
based
on
the
NAWQA
database,
with
the
exception
of
the
7
ppb
concentration.
The
highest
reported
value
in
the
NAWQA
database
is
5.5
ppb.
The
value
of
7
ppb
does
not
come
from
the
NAWQA
database
but
from
the
report
by
Werner
et
al.
(2000).
In
fact,
a
maximum
carbaryl
concentration
of
8.4
ppb
was
reported
for
surface
water
samples
in
the
California
DPR
surface
water
database
(see
discussion
section).
The
sources
of
the
information
should
not
be
mixed,
or
the
source
of
the
information
should
be
explicitly
stated.
EFED
Response:
EFED
concurs
with
the
registrant's
comments.
The
text
has
been
revised
to
read
"Surface
water
monitoring
studies
show
that
carbaryl
is
the
second
most
widely
detected
insecticide
after
diazinon.
Carbaryl,
at
typically
low
concentrations,
is
found
in
greater
than
20
%
of
surface
samples
in
NAWQA
studies
at
concentrations
up
to
5.5
ppb.
Carbaryl
is
detected
more
frequently
in
nonagricultural
areas
(about
40%)
then
in
agricultural
areas
(about
5
%).
A
maximum
carbaryl
concentration
of
8.4
ppb
was
reported
for
surface
water
samples
in
the
California
DPR
surface
water
database.
Carbaryl
is
generally
not
widely
detected
in
groundwater
monitoring
studies
though
some
studies
have
found
concentrations
of
up
to
several
hundred
ppb.
Concentrations
as
high
as
610
:
g/
L
have
been
detected
in
one
case
but
typical
groundwater
concentrations
are
much
lower.
NAWQA
47
studies
have
found
that
about
1
%
of
groundwater
samples
have
measurable
levels
(>
0.003
:
g/
L)
of
carbaryl,
with
a
maximum
concentration
of
0.02
:
g/
L.
Targeted
studies
designed
to
measure
carbaryl
in
groundwater
are
not
available."
Drinking
Water
Exposure
Assessment
Page:
30
Paragraph:
2
Line:
3
4
EPA
comment:
Carbaryl
is
the
second
most
commonly
detected
insecticide
in
surface
water,
and
can
be
expected
to
contaminate
drinking
water
derived
from
surface
water
bodies.
Aventis'
response:
The
surface
water
monitoring
program
conducted
by
Aventis
shows
an
insignificant
impact
of
carbaryl
on
drinking
water.
EFED
Response:
EFED's
interpretation
of
the
surface
water
monitoring
program
conducted
by
Aventis
has
been
discussed
previously
in
this
document.
Page:
30
Paragraph:
2
Line:
7
EPA
comment:
The
maximum
reported
value
was
7.0
µg
/L.
Aventis'
response:
The
maximum
value
reported
in
the
NAWQA
database
is
5.5
µg
/L.
The
only
carbaryl
detection
reported
in
the
study
by
Werner
et
al.
(2000)
was
7.0
µg
/L.
The
maximum
value
reported
in
the
California
DPR
Surface
Water
database
is
8.4
µg/
L.
Since
all
of
the
statistics
made
in
this
paragraph
refer
to
the
NAWQA
data,
the
reference
to
the
maximum
reported
concentration
should
be
5.5
µg
/L.
EFED
Response:
EFED
concurs
with
the
registrant's
comments.
The
text
has
been
revised
to
read
"The
maximum
reported
value
in
surface
water
was
8.4
µg/
L."
Page:
30
Paragraph:
4
Line:
2
EPA
comment:
Older
studies
using
GC
or
GC/
MS
generally
have
poor
recovery
and
quantitation
limits.
Because
of
this
difficulty
in
analysis
the
actual
concentration
of
carbaryl
in
groundwater
and
surface
waters
may
be
higher
than
reported.
48
Aventis'
response:
The
basis
for
making
this
generalization
is
not
readily
apparent
and
these
statements
should
be
removed.
Comments
regarding
the
recovery
reported
for
the
GC/
MS
method
used
in
the
NAWQA
survey
are
made
below
in
reference
to
statements
made
on
page
34
paragraph
5,
and
are
elucidated
in
the
discussion
section
at
the
end
of
this
response
document.
The
method
detection
limit
(MDL)
reported
for
the
GC/
MS
method
used
for
the
NAWQA
program
is
0.003
ppb
(Zaugg
et
al.,
1995;
Larson
et
al.
,
1999).
The
limit
of
detection
for
the
HPLC/
MS/
MS
method
used
in
the
carbaryl
surface
water
monitoring
study
being
conducted
by
the
registrant
(LOD,
0.002
ppb;
LOQ
0.030
ppb)
is
similar
to
the
GC/
MS
method
used
for
the
NAWQA
program.
In
addition
to
the
GC/
MS
method
used
in
the
NAWQA
program,
carbaryl
was
also
analyzed
by
HPLC/
photodiode
array
detection
in
a
limited
number
of
samples
with
a
MDL
of
0.008
(Werner
et
al.,
1996).
Therefore,
the
quantification
limits
reported
for
the
GC/
MS
method
used
to
generate
a
majority
of
the
carbaryl
data
in
the
NAWQA
database
is
very
similar
to
the
quantification
limits
for
available
HPLC
methods.
See
the
discussion
section
at
the
end
of
this
response
document
for
a
summary
of
the
available
NAWQA
data
obtained
by
the
GC/
MS
and
HPLC/
PDA
methods.
EFED
Response:
EFED
has
concerns
that
poor
detection
limits
in
the
past
may
have
underestimated
the
concentration
of
carbaryl
in
surface
and
groundwater.
However,
a
sentence
has
been
added
to
the
paragraph
stating
"More
recent
studies
using
HPLC/
MS
should
provide
better
data
on
the
true
extent
and
magnitude
of
water
contamination
from
the
use
of
carbaryl."
Page:
30
Paragraph:
4
Line:
4
EPA
comment:
More
recent
studies
using
HPLC/
MS
should
provide
better
data
on
the
true
extent
and
magnitude
of
water
contamination
from
the
use
of
carbaryl.
Aventis'
response:
Aventis
believes
that
our
ongoing
targeted
surface
water
monitoring
program
using
HPLC/
MS/
MS
accurately
reflects
the
extent
and
magnitude
of
carbaryl
exposure
in
drinking
water
derived
from
surface
water.
EFED
Response:
EFED
agrees
that
the
ongoing
study
applies
more
appropriate
analytical
methods.
The
limitations
of
the
study
have
been
discussed
elsewhere.
49
Drinking
Water
Modeling
Page:
31
Paragraph:
carried
over
from
page
30
Line:
8
EPA
comment:
A
partial
list
of
input
parameters
for
the
PRZM/
EXAMS
modeling
are
given
in
Table
4.
Aventis'
response:
The
partial
list
of
input
parameters
in
Table
4
includes
multiple
conservative
assumptions
likely
to
lead
to
significant
over
estimation
of
the
potential
surface
water
concentrations
of
carbaryl.
EFED
Response:
The
modeling
was
done
following
EFED
policy
and
standard
procedures.
EFED
concurs
with
the
registrant
that
the
PRZM/
EXAMS
model
includes
a
number
of
conservative
assumptions.
Page:
31
Paragraph:
2
Line:
1
EPA
comment:
For
the
Index
Reservoir
scenario
using
maximum
label
rates,
acute
EEC
values
ranged
from
19
µg/
L
from
sugar
beets
to
494
µg/
L
for
oranges
(Table
6).
Aventis'
response:
Table
6
on
page
33
shows
a
concentration
of
19
µg/
L
for
sugar
beets
treated
with
the
maximum
label
rate
of
2
x
1.5
lb
ai,
not
10
as
stated
in
this
sentence.
A
low
EEC
value
of
9
µg/
L
for
sugar
beets
results
from
the
"maximum
reported"
application
scenario
of
1
x
1.2
lb
ai/
A.
EFED
Response:
EFED
concurs
with
the
registrant's
comment.
The
text
had
been
revised
to
present
more
generalized
ranges
and
reads
".
.
.
acute
EEC
values
ranged
from
about
10
µg/
L
from
sugar
beets
to
about
500
µg/
L
from
citrus
(Table
6)."
Page:
31
Paragraph:
2
Line:
3
EPA
comment:
Chronic
EECs
ranged
from
about
1
to
28
µg/
L.
50
Aventis'
response:
Table
6
on
page
33
shows
that
this
is
correct
when
considering
all
of
the
model
scenarios.
However,
either
the
same
maximum
label
rate
reference
should
be
used
as
in
the
preceding
sentence
(in
which
case
the
minimum
chronic
EEC
would
be
2),
or
the
basis
for
the
preceding
sentence
should
be
changed
from
the
maximum
label
rate
to
include
all
application
scenarios
to
keep
the
comparisons
consistent.
EFED
Response:
EFED
concurs
with
the
registrant's
comments.
The
text
has
been
revised
and
now
reads
"Chronic
EECs
ranged
from
about
2
to
28
µg/
L."
Page:
31
Paragraph:
2
Line:
6
EPA
comment:
It
is
highly
unlikely
that
any
but
the
most
extensive
targeted
monitoring
would
capture
the
actual
peak
concentrations.
Aventis'
response:
The
role
of
a
peak
concentration
in
dietary
exposure
assessment
is
undergoing
reexamination
within
EPA.
The
current
policy
of
EPA
appears
to
define
a
certain
percentile
as
an
appropriate
value
for
use
in
screening
assessments,
but
the
exact
percentile
to
be
used
is
being
currently
set
by
EPA
management.
(The
most
recent
documents
from
EPA
cite
the
95
th
or
99
th
percentile.)
For
more
comprehensive
assessments,
a
distribution
of
values
is
preferred.
EFED
Response:
EFED
further
qualifies
its
statement
by
saying
"The
results
of
the
modeling
provide
a
very
conservative,
though
not
unreasonable,
estimate
of
possible
concentrations
in
drinking
water.
A
more
detailed
assessment
of
the
source
of
water
used
to
provide
drinking
water
and
the
relationship
between
the
areas
where
carbaryl
is
used
and
surface
water
sources
is
required
to
more
accurately
evaluate
possible
human
exposures."
Page:
31
Paragraph:
2
Line:
7
EPA
comment:
The
results
of
the
modeling
provide
a
conservative,
though
not
unreasonable,
estimate
on
possible
concentrations
drinking
water.(
sic)
Aventis'
response:
The
modeling,
performed
according
to
EPA
procedures,
provides
an
upper
bound
estimate
on
potential
concentrations
in
drinking
water
from
surface
water.
Whether
the
modeling
estimates
are
reasonable
depends
on
the
specific
assumptions.
For
carbaryl,
the
three
year
monitoring
program
(conducted
according
to
EPA
and
ILSI
guidance
available
at
the
time
51
the
study
was
started)
shows
that
the
model
calculations
are
unreasonable.
These
conservative
assumptions
include
a
3x
factor
on
both
the
aerobic
soil
and
aerobic
aquatic
half
lives,
assuming
the
maximum
drift
rate
for
aerial
applications
throughout
the
county
(in
Florida
citrus
almost
all
applications
are
by
air
blast
with
ground
equipment),
and
the
application
rate
over
a
watershed.
The
conservative
nature
of
the
application
assumption
alone
probably
results
in
an
overprediction
by
at
least
two
orders
of
magnitude.
The
modeling
calculations
assume
an
application
rate
of
17.4
lbs/
acre
of
watershed
annually.
In
Hardee
County,
the
county
with
the
highest
usage
of
carbaryl,
the
average
use
rate
on
a
countywide
basis
is
only
0.31
lb/
acre
(See
Appendix
II).
In
Manatee
County,
the
county
with
the
highest
usage
containing
a
watershed
used
to
supply
drinking
water,
the
average
rate
on
a
countywide
basis
is
0.027
lb/
acre.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
as
noted
in
the
previous
response,
the
text
has
been
revised
and
now
reads
"The
results
of
the
modeling
provide
a
[very]
conservative,
though
not
unreasonable,
estimate
of
possible
concentrations
[in]
drinking
water."
Page:
31
Paragraph:
2
Line:
8
EPA
comment:
A
more
detailed
assessment
of
the
source
of
water
used
to
provide
drinking
water
and
the
relationship
between
the
areas
where
carbaryl
is
used
and
surface
water
sources
is
required
to
more
accurately
evaluate
possible
human
exposures.
Aventis'
response:
As
mentioned
by
EPA
in
this
document,
ground
water
is
the
source
of
the
majority
of
Florida
drinking
water.
Many
of
the
counties
with
the
highest
use
of
carbaryl
contain
no
watersheds
used
to
provide
drinking
water.
As
discussed
more
fully
in
Appendix
I,
the
watershed
supplying
the
Manatee
County
Water
Treatment
Plant
appears
to
have
the
most
carbaryl
usage
of
drinking
water
watersheds
in
Florida.
EFED
Response:
The
registrant's
response
is
expressing
their
perspective
on
the
likelihood
that
watersheds
in
particular
areas
serve
as
drinking
water
sources;
the
comments
do
not
reflect
an
error
in
the
EFED
risk
assessment.
52
Water
Treatment
Effects
Page:
31
Paragraph:
3
Line:
8
EPA
comment:
Since
relatively
(sic)
few
water
treatment
facilities
in
the
U.
S.
use
ozone
the
limited
data
available
do
not
indicate
that
carbaryl
is
likely
to
be
degraded
in
the
majority
of
treatment
plants.
Aventis'
response:
The
monitoring
program
conducted
by
the
registrant
shows
that
removal
occurs
in
some
treatment
plants.
The
effect
of
treatment
seemed
to
be
greater
in
systems
using
carbon
treatment.
EFED
Response:
The
design
of
the
water
monitoring
study
does
not
allow
the
results
to
be
used
to
evaluate
treatment.
For
example,
raw
and
treated
water
samples
were
not
collected
from
the
same
mass
of
water,
and
treated
water
was
not
analyzed
for
all
sampling
periods.
Treated
water
was
found
to
have
higher
concentration
in
at
least
one
case.
The
limitations
of
the
study
have
been
discussed
elsewhere.
Page:
33
Table
6
EPA
comment:
Drinking
Water
EECs
(Table
6
entitled)
Aventis'
response:
Many
of
the
comments
for
this
table
are
similar
to
those
for
the
EECs
for
ecological
risk
found
in
Table
5.
The
PRZM
model
input
parameters
for
the
Index
Reservoir
scenarios
were
received
as
an
electronic
copy
of
a
draft
of
Appendix
B.
These
input
files
are
very
useful
for
assessing
the
scenarios
that
have
been
modeled.
It
would
be
useful
to
add
another
column
to
Table
6
to
specify
which
method
of
application
was
used
to
generate
the
EECs
(and
thus
the
application
efficiency
and
spray
drift
values).
It
would
be
of
benefit
for
the
Agency
to
state
which
of
the
carbaryl
labels
were
used
to
develop
the
"maximum"
label
application
rate
scenarios.
There
are
a
number
of
errors
in
the
input
parameters
(noted
below)
that
would
lead
to
changes
in
the
calculated
EECs
and
therefore
the
risk
quotients
for
these
uses.
The
model
parameters
listed
in
the
electronic
draft
of
Appendix
B
show
that
the
"average"
scenarios
for
citrus
and
apples
were
conducted
using
aerial
applications.
Few
applications
to
these
crops
are
made
aerially.
Therefore,
the
model
results
over
estimate
the
contributions
from
spray
drift
since
the
"average"
applications
to
these
crops
are
made
using
ground
airblast
equipment
with
a
spray
drift
of
6.3%
versus
aerial
applications
with
a
spray
drift
of
16%.
53
The
"maximum
label
rate"
application
scenario
for
apples
that
is
allowed
by
the
Sevin
brand
XLR
PLUS
label
(E.
P.
A.
Reg.
No
264
333),
the
Sevin
brand
80WSP
and
CHIPCO
Sevin
brand
80WSP
labels
(E.
P.
A.
Reg.
No
264
526)
and
the
CHIPCO
Sevin
brand
SL
label
(E.
P.
A.
Reg.
No
264
335)
is
5
applications
at
3
lb
ai/
A/
application
made
every
14
days.
The
scenario
used
in
the
model
applies
less
than
the
maximum
amount
of
product
allowed
by
the
labels.
In
addition,
application
timing
was
used
in
the
modeling
for
the
index
reservoir
scenario
(applications
made
by
air
every
4
days)
that
would
be
a
violation
of
the
Aventis
labels
which
restrict
applications
to
a
minimum
of
every
14
days.
The
"average"
scenario
for
sweet
corn
in
Ohio
should
be
3
applications
at
1.1
lb
ai/
A/
application
(as
noted
in
the
memo,
"Average
application
rate
from
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD")
and
not
the
2
applications
at
3.4
lb
ai/
A/
application
as
listed
in
the
table.
The
PRZM
input
file
shows
the
correct
inputs
of
3
applications
at
1.1
lb
ai/
A/
application.
The
"average"
scenario
for
sugar
beets
in
Minnesota
should
be
1
application
at
1.3
lb
ai/
A/
application
(as
noted
in
the
memo,
"Average
application
rate
from
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD")
and
not
1
application
at
1.5
lb
ai/
A/
application
as
listed
in
the
table
and
the
PRZM
input
file.
The
"Citrus"
scenario
would
be
more
appropriately
labeled
Oranges.
For
the
average
scenario,
the
3.4
lb
ai/
A/
application
rate
listed
in
Table
5
is
for
oranges
(as
noted
in
the
memo,
"Average
application
rate
from
Quantitative
Usage
Analysis
for
Carbaryl,
prepared
July
21,
1998
by
Frank
Hernandez,
OPP/
BEAD"),
which
is
the
highest
"average"
application
rate
for
any
type
of
citrus.
Therefore,
this
"average"
scenario
for
oranges
is
at
the
high
end
for
all
citrus
and
overestimates
the
EECs
for
use
in
the
other
citrus
crops.
"Average"
application
rates
for
other
citrus
as
listed
in
the
memo
are:
Lemons
–
1.3
applications
at
2.7
lb
ai/
A/
appl
Grapefruit
–
1.6
applications
at
1.4
lb
ai/
A/
appl
Citrus,
other
–
1.8
applications
at
1.8
lb
ai/
A/
appl
EFED
Response:
EFED
used
available
data
from
the
Biological
and
Economic
Assessment
Division
(BEAD)
in
2001
to
develop
the
risk
assessment.
However,
the
recommended
changes
would
not
substantially
change
EFED's
risk
assessment;
therefore,
the
table
has
not
been
significantly
revised
other
than
changing
"citrus"
to
read
"oranges".
Ground
Water
Resources
Page:
34
Paragraph:
carried
over
from
page
33
Line:
3
EPA
comment:
U.
S.
EPA.
Pesticides
in
Groundwater
Database
(Jacoby
et
al.,
1992)
54
Aventis'
response:
This
reference
is
not
provided
in
the
reference
list.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
reference
section
has
been
revised
to
include
the
following
reference:
Jacoby,
H.,
C.
Hoheisel,
J.
Karrie,
S.
Lees,
L.
Davies
Hilliard,
P.
Hannon,
R.
Bingham,
E.
Behl,,
D.
Wells,
and
E.
Waldman,
1992.
Pesticides
in
groundwater
database:
a
compilation
of
monitoring
studies:
1971
1991
National
Summary.
EPA
734
12
92
001.
Page:
34
Paragraph:
3
Line:
3
EPA
comment:
Detections
were
from
(sic)
mainly
from
three
use
sites:
wheat
(5.8
%
of
well
samples
from
wheat
land
use),
orchards
and
vineyards
(1.7
%
of
well
samples
from
orchard
and
vineyard
land
use),
and
urban
(1.8%
of
urban
groundwater
samples).
Aventis'
response:
Updated
information
(noted
below)
is
not
summarized
in
the
same
manner
as
in
this
statement,
so
direct
comparisons
cannot
be
made
easily.
However,
the
updated
information
indicates
a
similar
pattern
of
low
concentrations
of
carbaryl
detections
in
a
limited
number
of
ground
water
resources.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised
to
read
"Detections
were
mainly
from
three
use
sites:
wheat
(5.8
%
of
well
samples
from
wheat
land
use
),
orchards
and
vineyards
(1.7
%
of
well
samples
from
orchard
and
vineyard
land
use),
and
urban
(1.8%
of
urban
groundwater
samples).
Data
on
pesticides
in
groundwater
were
reviewed
by
Kolpin
et
al.
(1998)
and
updated
information
is
available
at:
http://
water.
wr.
usgs.
gov/
pnsp/
pestgw/."
Page:
34
Paragraph:
3
Line:
6
EPA
comment:
Limitations
in
analytical
methodology
(described
elsewhere)
apply
to
groundwater
sample
analysis
also
suggesting
that
there
(sic)
actual
maximum
concentrations
and
extent
of
contamination
may
be
significantly
higher.
Aventis'
response:
This
statement
is
misleading
and
should
be
deleted.
The
validation
of
the
most
widely
used
GC/
MS
method
for
the
data
contained
in
NAWQA
show
recoveries
of
86
to
94%
at
spiking
levels
of
0.1
to
1.0
µg/
L
with
an
MDL
of
0.003
µg/
L.
The
HPLC
method
validation
reported
recoveries
of
58
to
64%
%
at
spiking
levels
of
0.1
to
1.0
µg/
L
with
an
MDL
of
0.018
µg/
L.
Furthermore,
using
the
GC/
MS
method,
a
mean
recovery
of
115%
was
found
for
field
matrix
55
spikes
of
carbaryl
at
spiking
levels
of
0.1
µg/
L.
With
the
GC/
MS
method
MDL
of
0.003
µg/
L
and
a
mean
recovery
of
115%
for
the
field
matrix
spikes,
this
method
cannot
reasonably
be
characterized
as
stated
by
EPA.
Additional
details
of
the
method
validations
and
field
matrix
spikes
are
provided
in
the
`Discussion
Section'
at
the
end
of
this
response.
EFED
Response:
EFED
has
revised
the
text
to
read
"Because
of
limitation
in
the
analytical
methods
used
there
is
some
uncertainty
in
the
quantitative
accuracy
of
carbaryl
analysis."
Page:
34
Paragraph:
3
Line:
last
EPA
comment:
…and
updated
information
is
available
at:
.
Aventis'
response:
This
web
page
was
last
updated
in
1998.
A
more
recent
update
by
Kolpin
was
posted
June
11,
2001
at:
http://
water.
wr.
usgs.
gov/
pnsp/
pestgw/
and
is
the
source
of
the
updated
information
included
in
the
`Discussion
Section'
at
the
end
of
this
response.
EFED
Response:
EFED
concurs
with
the
registrant's
comment
and
the
website
has
been
updated
to
read
"
http://
water.
wr.
usgs.
gov/
pnsp/
pestgw/".
Surface
Water
Resources
Monitoring
Data
Page:
34
Paragraph:
4
Line:
5
6
EPA
comment:
Because
of
limitation
in
the
analytical
methods
used
there
is
some
question
as
to
the
accuracy
of
carbaryl
analysis.
Aventis'
response:
This
generalized
statement
needs
to
be
qualified
or
deleted.
Whereas
the
authors
of
reports
written
as
part
of
the
NAWQA
program
have
been
clear
about
the
potential
limitations
of
the
quantitative
nature
of
the
carbaryl
data
in
the
database,
they
have
also
been
clear
about
the
validity
of
the
qualitative
nature
of
the
data.
The
use
of
the
multi
residue
method
in
the
NAWQA
program
does
have
some
limitations
as
a
result
of
the
large
numbers
of
diverse
pesticides
and
degradation
products
that
they
are
monitoring.
However,
the
QC/
QA
data
generated
as
part
of
the
NAWQA
program
(described
in
the
discussion
section
on
surface
56
water
at
the
end
of
this
response)
demonstrate
the
validity
of
the
detections
of
carbaryl
in
the
studies.
The
monitoring
study
conducted
by
the
registrant,
and
reported
in
this
section,
does
not
have
the
same
potential
limitations
in
the
analytical
method
since
the
method
is
looking
specifically
for
carbaryl.
Therefore,
the
analytical
method
used
by
the
registrant
does
not
raise
questions
about
the
accuracy
of
the
carbaryl
analysis.
EFED
Response:
EFED
concurs
with
the
registrant's
comment
and
the
text
has
been
revised
to
read
"Because
of
limitations
in
the
analytical
methods
used
there
is
some
uncertainty
in
the
quantitative
accuracy
of
carbaryl
analysis."
Page:
34
Paragraph:
4
Line:
5
6
EPA
comment:
Poor
analytical
methods
probably
have
resulted
in
lower
detection
rates
and
lower
concentrations
than
actually
present.
Aventis'
response:
This
generalized
statement
should
be
deleted
for
reasons
provided
above
and
in
the
discussion
section.
NAQWA
(sic)
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
sentence
has
been
deleted.
Additionally,
all
references
to
the
National
Water
Quality
Assessment
(NAWQA)
acronym
have
been
corrected.
Page:
34
35
Paragraph:
5
Lines:
5
8
EPA
comment:
Carbaryl
analytical
results
are
fairly
poor,
with
a
typical
mean
percent
recovery
of
24%
(
F
=
15)
in
laboratory
quality
control
samples,
and
a
method
detection
limit
(MDL)
of
0.003
ug/
L.
This
suggests
that
the
values
reported
do
not
represent
the
maximum
concentrations
that
exist,
and
that
surface
water
contamination
may
be
more
widespread
than
the
data
show.
Aventis'
response:
These
statements
are
misleading
and
should
be
updated
with
further
quality
control
data
supplied
by
NAWQA.
57
A
discussion
of
the
analytical
method
used
in
the
NAWQA
program
is
presented
in
the
USGS
Open
File
Report
95
181
(see
Zaugg
et
al.
(1995)
in
references).
The
mean
percent
recovery
of
24%
noted
above
can
be
found
in
Table
9
of
this
report
and
is
by
no
means
"typical".
A
mean
recovery
value
of
24%
was
reported
for
reagent
grade
water
fortified
at
a
level
of
0.03
:
g/
L
with
a
method
detection
limit
said
to
be
0.003
:
g/
L.
Additional
recoveries
for
fortified
water
samples
(reagent
grade,
ground
and
surface
waters)
ranged
from
10
to
202%
(see
discussion
section).
The
carbaryl
data
in
thenot
because
the
carbaryl
concentrations
are
underestimated.
Additional
evaluations
of
field
blank,
field
matrix
spike
and
lab
control
spike
samples
as
part
of
the
NAWQA
program
can
be
found
in
a
provisional
report
by
Martin
(1999).
This
report
demonstrates
the
lack
of
detection
of
carbaryl
in
100%
of
the
field
blanks,
and
median
recoveries
of
94.4%
in
306
field
matrix
spikes
and
93.0%
in
1000
lab
control
spikes,
each
at
spiking
levels
of
0.1
:
g/
L.
These
data
suggest
an
adequate
level
of
detection
of
carbaryl
in
the
method
used
in
the
NAWQA
survey
of
surface
and
ground
water.
See
the
additional
discussion
at
the
end
of
this
document
for
further
information
regarding
recoveries
in
spiked
surface
and
ground
water.
EFED
Response:
EFED
has
revised
the
text
to
read
"Carbaryl
is
the
second
most
widely
detected
insecticide
after
diazinon
in
the
USGS
NAWQA
program
(http://
water.
usgs.
gov/
nawqa/
nawqa_
home.
html).
Carbaryl
was
detected
in
46%
of
36
NAWQA
study
units
between
1991
and
1998.
The
reported
concentrations
are
believed
to
be
reliable
detections
but
have
greater
than
average
uncertainty
in
quantification.
The
data
in
the
NAWQA
database
are
amended
with
an
"E"
qualifier
to
indicate
the
variability
found
in
the
analysis.
This
suggests
that
the
reported
values
may
not
represent
the
maximum
concentrations
that
exist.
Page:
35
Paragraph:
2
Line:
7
EPA
comment:
…at
about
0.1
percent
of
the
amount
used
in
the
basins
(Larson
et
al.,
1999)
.
The
estimated
carbaryl
use
on
in
agricultural
applications
is
about
4
million
pounds
suggesting
that
400,000
pounds
are
delivered
to
the
nations
streams
draining
agricultural
areas.
Aventis'
response:
This
estimated
use
of
carbaryl
for
agricultural
applications
over
estimates
the
use
of
carbaryl
by
about
1
million
pounds.
BEAD
and
USGS
data
cited
on
pages
6
and
7
are
consistent
with
lower
total
pounds
of
carbaryl
applied.
In
addition,
0.1
percent
of
4
million
pounds
would
be
4,000
pounds,
not
400,000
pounds.
If
the
1987
–
1996
average
of
2.5
million
pounds
carbaryl
is
used
in
the
calculation,
the
total
load
suggested
to
be
delivered
to
streams
draining
agricultural
areas
would
be
2,500
pounds.
58
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised
to
read
"A
significant
portion
of
the
total
carbaryl
applied
was
transported
to
streams.
In
areas
with
high
agricultural
use
the
load
measured
in
surface
waters
was
relatively
consistent
across
the
country
at
about
0.1
percent
of
the
amount
used
in
the
basins
(Larson
et
al.,
1999)
http://
water.
wr.
usgs.
gov/
pnsp/
rep/
wrir984222/
load.
html.
The
estimated
carbaryl
use
on
in
agricultural
applications
is
about
2.5
million
pounds
suggesting
that
2,500
pounds
are
delivered
to
the
nations
streams
draining
agricultural
areas.
Registrant
Monitoring
Study
Page:
35
Paragraph:
4
Line:
11
EPA
comment:
Carbaryl
was
analyzed
by
HPLC/
MS
with
a
limit
of
detection…
Aventis'
response:
The
analytical
method
used
by
the
registrant
in
the
surface
water
monitoring
study
uses
tandem
mass
spectrometry
(MS/
MS)
as
the
detection
method.
This
type
of
detection
involves
quantification
of
"daughter"
ions
from
a
selected
mass
fragment
and
is
more
selective
than
an
MS
method.
Therefore,
to
accurately
reflect
these
differences,
the
method
should
be
labeled
as
HPLC/
MS/
MS.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised
to
read
"Carbaryl
was
analyzed
by
HPLC/
MS/
MS
with
a
limit
of
detection
of
0.002
ppb
(2
ppt)
and
a
limit
of
quantitation
(LOQ)
of
0.030
ppb
(30
ppt)."
Page:
36
Paragraph:
3
Line:
9
EPA
comment:
In
several
cases
finished
water
had
higher
concentration
than
raw
water,
and
finished
water
had
detectable
carbaryl
when
the
raw
did
not.
The
highest
concentration
measured
was
in
finished
water
(0.18
ppb).
Raw
water
sampled
at
the
same
time
had
much
lower
concentration
(0.010).
59
Aventis'
response:
This
statement
is
misleading
and
certainly
does
not
consider
the
analytical
uncertainty
for
concentrations
below
the
level
of
quantification
and
near
the
level
of
detection.
There
were
only
two
cases
when
finished
water
was
greater
than
raw
water
when
the
concentrations
in
finished
water
were
greater
than
0.01
ppb
(only
one
third
of
the
quantification
limit).
One
case
was
when
the
raw
water
was
0.009
ppb
and
the
finished
water
was
0.011
ppb.
These
two
analyses
are
essentially
equivalent,
especially
considering
that
they
are
only
about
a
third
of
the
quantification
limit.
The
other
case
was
at
the
Deerfield
community
water
system.
This
drinking
water
facility
uses
a
small
river
without
a
reservoir
as
a
source
for
a
small
Community
Water
System.
Farms
are
located
immediately
upstream
of
the
facility.
The
intake
is
also
not
continuous
(shut
down
over
weekends).
Therefore,
getting
a
matching
sample
is
quite
difficult,
especially
for
a
short
duration
spike
as
a
result
of
spray
drift,
summer
thunderstorm,
or
perhaps
a
spill
that
almost
immediately
enters
the
river
a
runoff
event.
The
rarity
of
this
event
is
demonstrated
by
the
absence
of
residues
of
this
magnitude
the
next
year
(2000).
Samples
collected
through
this
time
of
the
year
in
2001
also
do
not
indicate
a
similar
event.
Although
the
data
from
this
site
cannot
be
used
to
determine
the
peak
concentration,
the
data
provide
a
distribution
of
residues
through
the
three
year
period
which
will
define
up
to
the
99
th
percentile
concentration
of
the
distribution.
The
Deerfield,
Michigan
community
water
system
is
one
of
the
systems
in
which
the
greatest
variability
of
residues
would
be
expected.
Most
of
the
other
community
water
systems
are
located
on
larger
rivers,
lakes,
or
reservoirs.
Because
the
design
of
study
called
for
analysis
of
finished
water
only
when
there
were
residues
in
the
raw
water,
there
was
only
one
finished
sample
analyzed
when
the
raw
water
contained
no
residues.
This
sample
was
collected
at
the
Deerfield
community
water
system
at
the
sampling
interval
after
the
finding
of
0.16
ppb
in
the
Deerfield
system.
The
residue
level
in
this
sample
was
0.004
ppb.
The
difference
between
0.004
ppb
and
non
detect
is
insignificant,
and
if
real
can
probably
be
attributed
to
water
at
much
higher
concentrations
remaining
in
the
system
from
the
previous
week.
EFED
Response:
The
registrant's
comments
point
out
a
major
flaw
in
the
water
monitoring
study
design.
The
study
should
have
analyzed
finished
water
at
all
sampling
times.
Because
of
this
and
other
shortcomings
discussed
previously,
the
results
of
this
study
cannot
be
used
to
evaluate
the
effects
of
treatment
on
carbaryl.
Page:
36
Paragraph:
4
Line:
1
EPA
comment:
Non
targeted
monitoring,
such
as
the
NAWQA
program,
has
shown
much
higher
concentrations
occur
indicating
that
this
study,
while
useful,
can
not
be
used
to
describe
the
overall
distributions
that
occur
throughout
the
entire
use
area.
Aventis'
response:
60
The
targets
of
the
drinking
water
monitoring
conducted
by
the
registrant
and
the
NAWQA
program
are
different.
The
NAWQA
program
characterized
surface
water
concentrations
within
a
study
area
while
the
Aventis
drinking
water
monitoring
measured
residues
in
inlets
and
outlets
of
drinking
water
facilities.
Also
the
drinking
water
monitoring
program
considered
only
use
areas
with
drinking
water
supplies.
However,
for
FQPA
dietary
assessments,
the
appropriate
target
is
drinking
water
rather
than
surface
water.
The
main
reason
why
the
drinking
water
monitoring
study
did
not
show
residues
as
high
as
in
the
NAWQA
program
is
the
location
of
the
sampling
points.
Drinking
water
supplies
tend
to
be
located
on
larger
surface
water
bodies
than
NAWQA
sampling
points
(or
in
other
words,
the
intakes
for
community
water
systems
tend
to
be
downstream
of
NAWQA
sampling
points).
This
additional
time
allows
for
additional
degradation
and
dilution
to
occur.
Finding
the
highest
concentration
at
the
Deerfield,
Michigan
system
is
not
surprising
since
this
intake
is
on
one
of
the
smallest
surface
water
bodies
included
in
the
monitoring
study
(see
response
to
Page:
36,
Paragraph:
3,
Line:
9
above
for
a
more
detailed
explanation).
EFED
Response:
The
registrant's
comments
express
their
perspective
on
non
targeted
monitoring
studies
and
do
not
reflect
an
error
in
the
risk
assessment.
Page:
36
Paragraph:
4
Line:
4
EPA
comment:
This
study
does
not
provide
sufficient
information
to
allow
estimation
of
actual
peak
and
mean
concentrations
that
actually
occur
in
all
use
areas.
Aventis'
response:
Because
most
of
the
samples
did
not
contain
carbaryl
residues,
accurate
estimates
of
the
actual
peak
and
mean
concentrations
can
not
be
obtained.
However,
the
distributions
obtained
from
all
sites
can
be
used
to
define
up
to
the
99
th
percentile
concentration.
The
average
cannot
be
accurately
determined;
however,
the
time
weighted
average
is
only
slightly
above
the
limit
of
detection
(and
certainly
less
than
0.01
ppb)
at
all
20
sites.
The
peak
concentration
in
this
study
was
measured
at
a
community
water
system
on
a
small
river.
The
registrant
agrees
that
the
sampling
schedule
was
not
adequate
to
determine
the
true
peak
in
such
systems.
Most
of
the
other
community
water
systems
are
located
on
larger
rivers,
lakes,
or
reservoirs.
Therefore,
the
peak
values
are
not
likely
to
be
an
order
of
magnitude
greater
than
the
amounts
present
in
the
collected
samples.
The
distributions
obtained
in
this
study
are
suitable
for
use
in
dietary
exposure
assessments.
When
EPA
policy
establishes
what
percentile
concentration
is
an
appropriate
regulatory
endpoint,
then
these
percentiles
can
be
determined
for
each
of
the
community
water
systems
monitoring.
These
percentiles
can
then
be
compared
with
DWLOC
values
in
screening
assessments.
61
EFED
Response:
EFED
has
responded
previously
to
the
utility
of
Aventis'
water
monitoring
study.
Page:
37
Paragraph:
2
Line:
1
EPA
comment:
Only
limited
information
was
submitted
on
sampling
site
selection…
Aventis'
response:
The
summary
in
Appendix
I
of
this
response
provides
a
description
of
the
sites
considered
for
the
monitoring
study
and
the
rationale
for
the
selection
of
the
twenty
sites.
This
information
demonstrates
that
the
community
water
systems
selected
for
this
study
are
representative
of
the
systems
that
are
most
likely
to
contain
the
highest
concentrations
of
carbaryl
residues.
EFED
Response:
EFED
will
review
new
submissions
and
data
when
available.
This
does
not
represent
an
error
in
the
EFED
document
and
so
will
not
be
addresses
here.
It
will
be
addressed
in
an
appropriate
review
document
when
it
has
been
completed.
Page:
37
Paragraph:
3
Line:
3
EPA
comment:
This
should
include
an
explanation
of
why
this
study
did
not
observe
concentrations
as
high
as
those
found
in
other,
non
targeted
studies,
and
how
the
results
of
this
study
can
be
related
to
concentrations
that
occur
throughout
the
country.
Aventis'
response:
The
main
reason
why
the
drinking
water
monitoring
study
did
not
show
residues
as
high
as
in
the
NAWQA
program
is
the
location
of
the
sampling
points.
Drinking
water
supplies
tend
to
be
located
on
larger
surface
water
bodies
than
NAWQA
sampling
points
(or
in
other
words,
the
intakes
for
community
water
systems
tend
to
be
downstream
of
NAWQA
sampling
points).
This
additional
time
allows
for
additional
degradation
and
dilution
to
occur.
Finding
the
highest
concentration
at
the
Deerfield,
Michigan
system
is
not
surprising
since
this
intake
is
on
one
of
the
smallest
surface
water
bodies
included
in
the
monitoring
study
(see
response
to
Page:
36,
Paragraph:
3,
Line:
9
above).
Since
the
drinking
water
study
targeted
drinking
water
systems
in
high
use
watersheds,
the
data
from
this
study
are
representative
of
the
drinking
water
systems
most
likely
to
contain
carbaryl.
62
EFED
Response:
EFED
has
already
commented
on
the
utility
of
Aventis'
water
monitoring
study.
Please
refer
to
the
previous
discussions.
Sacramento
San
Joaquin
River
Delta
Page:
37
Paragraph:
4
Line:
4
5
EPA
comment:
Carbaryl
was
found
to
be
the
sole
causative
agent
at
one
of
20
sites…
The
toxicity
seemed
to
persist
for
several
days…
Aventis'
response:
The
statement
should
be
revised.
The
reference
cited
(Werner
et
al.,
2000)
lists
carbaryl
as
"the
primary
toxicant"
(not
as
the
"sole
causative
agent"),
even
though
an
unknown
was
also
found
at
the
same
time.
No
information
about
the
"unknown"
is
provided.
Both
conclusions
of
"sole
causative"
and
of
"primary
toxicant"
cannot
be
substantiated
without
further
evidence
about
the
nature
and
concentration
of
the
unknown.
Actually,
for
another
site
the
authors
concluded
about
the
unknown
found
there
"in
3
of
21
samples,
toxicity
observed
could
not
be
entirely
explained
by
the
identified
primary
toxicants."
Additionally,
it
is
at
least
questionable
if
the
analytical
method
employed
would
detect
all
potential
toxicants
beside
the
insecticides
it
was
set
up
for.
The
toxicity
seeming
to
persist
is
not
explained
or
substantiated
in
the
reference.
The
citation
of
such
dubious
results
should
be
removed
from
the
RED.
EFED
Response:
EFED
has
revised
the
text;
it
now
reads
"Carbaryl
was
found
to
be
the
[primary]
toxicant
at
one
of
20
sites
sampled
in
1995,
with
concentration
of
7.0
µg/
L."
Furthermore,
the
reference
cited
(Werner,
et
al.
2000)
is
taken
from
a
peer
reviewed
journal,
i.
e.,
Environmental
Toxicology
and
Chemistry,
which
EFED
does
not
consider
to
be
a
dubious
source.
6.0
Hazard
and
Risk
Assessment
for
Aquatic
Organisms
Hazard
assessment
for
Aquatic
organisms
Estuarine/
Marine
Fish
Page:
39
Paragraph:
2
Line:
6
EPA
comment:
…carbaryl
water
concentration
of
1.2
µg/
ml…
63
Aventis'
response:
To
be
consistent
with
the
rest
of
the
document
the
units
should
be
presented
in
ppm
("
carbaryl
water
concentration
of
1.2
ppm")
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised
to
read
"1.2
ppb".
Aquatic
Plants
Page:
40
Paragraph:
2
Line:
6
EPA
comment:
Guideline
122
2
is
not
fulfilled.
Aventis'
response:
The
chapter
should
be
revised.
As
detailed
above
(comments
to
Page
2
of
the
Memorandum),
studies
were
submitted
in
1992.
The
status
for
this
requirement
in
an
October
04,
2000
OPP
Guideline
Status
Report
(Chemical
Review
Management
System)
lists
the
guideline
122
2
status
as
"Acceptable/
Satisfied".
EFED
Response:
As
EFED
has
noted
previously
in
its
response
to
comments,
EPA
requires
data
on
5
aquatic
plant
species.
The
registrant
has
provided
data
on
only
two
of
the
five
species
that
were
classified
as
acceptable
and
as
having
fulfilled
guideline
test
requirements.
Therefore,
EFED
is
requesting
that
aquatic
plant
studies
be
repeated
following
EPA
guidelines.
Risk
Assessment
for
Aquatic
Organisms
Page:
40
Paragraph:
4
Line:
3
EPA
comment:
…corresponding
levels
of
concern
(LOCs)
is
presented
in
Appendix
D.
Aventis'
response:
The
risk
quotients
are
currently
listed
in
Appendix
C.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised;
the
sentence
now
reads
"A
detailed
analyses
of
risk
quotients
(RQs)
in
relation
to
their
corresponding
levels
of
concern
(LOCs)
is
presented
in
Appendix
C."
64
Estuarine/
Marine
Fish
Page:
42
Paragraph:
1
Line:
17/
18
EPA
comment:
Chronic
toxicity
studies
with
an
estuarine/
marine
fish
species
is
required.
Aventis'
response:
This
requirement
should
be
waived.
Given
the
relatively
short
half
life
of
carbaryl
in
the
aquatic
environment
and
the
low
acute
risk,
it
is
unlikely
that
estuarine/
marine
fish
species
would
be
exposed
to
a
chronic
risk.
EFED
Response:
This
is
not
an
error
and
is
more
appropriately
addressed
in
a
later
phase
of
the
reregistration
process.
Page:
42
Paragraph:
2
Line:
1
EPA
comment:
There
is
one
carbaryl
use
in
particular
that
presents
a
major
acute
and
chronic
risk
to
estuarine/
marine
fish.
Aventis'
response:
This
sentence
should
be
rephrased.
While
there
might
be
an
acute
risk
from
the
application
to
oyster
beds,
given
that
there
is
only
one
application
every
six
years
according
to
the
reference
cited
by
EPA,
it
is
improbable
that
estuarine/
marine
fish
would
be
exposed
to
a
chronic
risk.
EFED
Response:
In
a
study
by
Stonic
(1999)
application
of
carbaryl
to
mud
flats
in
Willapa
Bay,
Washington,
resulted
in
post
spray
carbaryl
concentrations
at
sprayed
sites
ranging
from
2,000
to
3,400
ppb
by
2
days
after
treatment
(DAT),
180
to
220
ppb
by
30
DAT,
and
86
120
ppb
by
60
DAT.
These
data
suggest
that
the
potential
for
chronic
exposure
to
estuarine/
marine
fish
is
possible.
However,
EFED
has
rephrased
the
sentence
to
read
"There
is
one
carbaryl
use
in
particular
that
represents
a
potential
acute
and
chronic
risk
to
estuarine/
marine
fish."
The
full
reference
for
these
data
is:
Stonic,
Cynthia.
1999.
Screening
Survey
of
Carbaryl
(Sevin
™
)
and
1
naphthol
Concentrations
in
Willapa
Bay
Sediments.
Washington
State
Department
of
Ecology.
Publication
No.
99
323.
65
7.0
Hazard
and
Risk
Assessment
for
Terrestrial
Organisms
Hazard
Assessment
for
Terrestrial
Organisms
Mammalian
Page:
46
Paragraph:
4
Line:
1
EPA
comment:
With
a
rat
LD50
of
307
mg/
kg…
Aventis'
response:
Typographical
error,
the
rat
LD50
is
301
mg/
kg.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
has
corrected
the
text
to
indicate
a
rat
LD50
of
301
mg/
kg.
Risk
Assessment
for
Terrestrial
Organisms
Avian
Risk
Nongranular
Formulations
Page:
47
Paragraph:
4
Line:
5
EPA
comment:
…levels
of
concern
(LOCs)
is
presented
in
Appendix
D.
Aventis'
response:
The
risk
quotients
are
currently
listed
in
Appendix
C.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
has
revised
the
text
to
reflect
that
risk
quotients
and
their
associated
levels
of
concern
(LOCs)
are
presented
in
Appendix
C.
Page:
48
Paragraph:
1
Line:
3
EPA
comment:
…
for
34
of
43
uses
at
maximum
reported
rates,
and
for
37
of
72
uses
at
"average"
rates.
(Appendix
D,
…
Aventis'
response:
The
risk
quotients
are
currently
listed
in
Appendix
C.
66
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
has
revised
the
text
to
reflect
that
risk
quotients
and
their
associated
levels
of
concern
(LOCs)
are
presented
in
Appendix
C.
Granular
Formulations
Page:
48
Paragraph:
2
Line:
5
EPA
comment:
…for
any
of
the
granular
carbaryl
uses
(Appendix
D,
Table
6).
Aventis'
response:
The
risk
quotients
are
currently
listed
in
Appendix
C.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
has
revised
the
text
to
reflect
that
risk
quotients
and
their
associated
levels
of
concern
(LOCs)
are
presented
in
Appendix
C.
Mammalian
Risk
Risk
to
Herbivores/
Insectivores:
Nongranular
Formulations
Risk
Quotients
for
Herbivores/
Insectivores
Based
on
Less
than
Maximum
Label
Use
Rates
Page:
48
Paragraph:
3
Line:
3
&
4
EPA
comment:
…
(Appendix
D,
Table
10a)
and
maximum
reported
(Doane
data)
use
rates
data
available
for
43
uses
(Appendix
D,
Table
10b)
Aventis'
response:
The
risk
quotients
are
currently
listed
in
Appendix
C.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
has
revised
the
text
to
reflect
that
risk
quotients
and
their
associated
levels
of
concern
(LOCs)
are
presented
in
Appendix
C.
67
Risk
Quotients
for
Herbivores/
Insectivores
Based
on
Maximum
Label
Use
Rates
Page:
48
Paragraph:
6
Line:
1
EPA
comment:
Carbaryl
is
moderately
toxic
to
small
mammals
on
an
acute
oral
basis
(rat
LD50
=
307
mg/
kg)
Aventis'
response:
Typographical
error,
the
rat
LD50
is
301
mg/
kg.
By
using
the
lower
LD50
all
acute
mammalian
risk
quotients
will
change
slightly.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
has
corrected
the
text
to
indicate
a
rat
LD50
of
301
mg/
kg.
The
mammalian
risk
quotient
tables
in
Appendix
C
and
the
ranges
reported
in
the
text
have
been
revised
to
reflect
the
modest
change
in
numbers.
Page:
49
Paragraph:
1
Line:
3
EPA
comment:
…corresponding
levels
of
concern
(LOCs)
is
presented
in
Appendix
D.
Aventis'
response:
The
risk
quotients
are
currently
listed
in
Appendix
C.
EFED
Response:
EFED
concurs
with
the
registrant's
comments.
The
sentence
has
been
revised
to
read
"A
detailed
analysis
of
mammalian
RQs
in
relation
to
their
corresponding
levels
of
concern
(LOCs)
is
presented
in
Appendix
C."
Risk
to
Granivores:
Nongranular
Uses
Chronic
risk:
Nongranular
Uses
Page:
50
Paragraph:
2
Line:
8
EPA
comment:
…summarized
in
Appendix
D,
Table
9.
Aventis'
response:
The
risk
quotients
are
currently
listed
in
Appendix
C.
68
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
has
revised
the
text
to
reflect
that
risk
quotients
and
their
associated
levels
of
concern
(LOCs)
are
presented
in
Appendix
C.
Reproduction
Effects
Page:
50
&
51
Paragraph:
4
/
1
EPA
comment:
(Review
of
alleged
reproduction
effects
of
carbaryl).
Aventis'
response:
The
paragraphs
should
be
changed.
The
literature
cited
in
these
paragraphs
show
ambivalent
results.
While
some
references
seem
to
support
the
claim
of
reproductive
effects,
other
references
do
not.
The
potential
for
reproductive
effects
in
mammals
was
evaluated
in
the
recently
submitted
2
generation
study
in
rats.
No
reproductive
effects
were
seen
in
this
guideline
study.
The
NOAEC
of
75
ppm
was
based
on
pup
mortality.
EFED
Response:
EFED
believes
that
the
chronic
effects
cited
from
the
open
literature
are
legitimate.
As
stated
previously,
chronic
reproductive
tests
have
resulted
in
effects
that
support
EFED's
concerns
regarding
the
endocrine
disrupting
potential
of
carbaryl.
EFED
believes
that
the
chronic
effects
cited
from
rat
developmental
studies,
i.
e.,
reduced
reproduction,
disturbances
in
spermatogenesis,
increased
resorption
of
embryos,
increased
incidence
of
infertility
in
females
and
underdeveloped
testes
in
males,
also
represent
serious
reproductive
effects
that
support
EFED's
concerns
regarding
the
chronic
reproductive/
developmental
toxicity
of
carbaryl.
Just
because
one
study
failed
to
show
similar
effects
to
another,
EFED
does
not
believe
that
it
would
be
reasonable
to
discount
the
validity
of
the
earlier
studies.
If
anything,
the
data
strongly
suggests
that
additional
data
are
needed
to
better
understand
the
likelihood
of
adverse
effects.
Page:
51
Paragraph:
4
EPA
comment:
Feeding
2
or
20
mg/
kg
of
carbaryl
to
pregnant
rhesus
monkeys
(Macacca
mulatta)
Aventis'
response:
This
paragraph
should
be
deleted.
As
there
are
no
native
monkey
species
in
the
U.
S.,
this
reference
is
irrelevant
for
U.
S.
wildlife
species.
Additionally,
the
reference
cited
is
only
a
brief
abstract
article
consisting
of
one
17
line
paragraph.
Such
information
should
not
be
the
basis
for
use
in
a
RED
risk
assessment.
69
EFED
Response:
The
basis
for
the
EFED
risk
assessment
is
the
mammalian
acute
(LD50
=
301
mg/
kg)
and
chronic
(NOAEC
=
80
ppm)
rat
toxicity
data.
The
data
from
rhesus
monkeys
are
used
to
further
characterize
risk.
While
the
registrant
is
correct
that
rhesus
monkeys
are
not
native
to
the
United
States,
these
animals
are
routinely
used
in
primate
research
and
are
considered
reasonable
surrogates
for
studying
the
effects
of
chemicals
on
humans.
9.0
References
(non
MRID)
Some
of
the
references
cited
in
EPA's
list
are
not
full
scientific
articles,
but
only
abstracts
from
meetings
(e.
g.
DeNorsica,
1973;
Doughtery
et
al.
,
1971,
Chapin
et
al.
1997).
Such
"publications"
should
not
be
used
as
references
considered
in
risk
assessments.
Without
a
sufficient
description
of
methods
and
a
presentation
of
detailed
results
these
studies
cannot
be
evaluated
to
determine
if
the
findings
are
or
are
not
scientifically
plausible.
Similarly,
at
least
three
of
the
references
(Gladenko
et
al.
1970,
Krylova
et
al.
1975,
Smirnov
et
al.
1971)
cited
as
proof
for
reproductive
toxicity
are
in
Russian
in
Cyrillic
writing
making
an
appropriate
and
timely
evaluation
difficult.
Due
to
the
limited
review
time
during
the
30
day
comment
period,
the
registrant
could
not
peruse
all
references.
A
more
detailed
response
will
be
provided
during
the
60
day
comment
period.
EFED
Response:
EFED
has
cited
literature
from
peer
reviewed
journals
and
considers
these
sources
to
be
reliable.
Furthermore,
the
registrant
is
providing
their
perspective
on
open
literature
and
is
not
citing
a
specific
error
in
the
risk
assessment.
Page:
59
EPA
comment:
Carmel,
R.
F.,
Imhoff,
J.
C.,
Hummel,
P.
R.,
Cheplick,
J.
M.
and
Donigan,
A.
S.,
1997.
Aventis'
response:
The
first
name
should
be
Carsel.
EFED
Response:
EFED
concurs
with
the
registrant's
comment
and
has
corrected
the
reference
to
reflect
the
correct
spelling
of
the
name
"Carsel".
70
Page:
59
EPA
comment:
Nkedi
Kizza
and
Brown
(1988)
Aventis'
response:
The
date
should
be
1998.
EFED
Response:
EFED
concurs
with
the
registrant's
comment
and
has
corrected
the
reference
to
reflect
the
correct
date
of
publication,
i.
e.,
1998.
Appendix
A:
Environmental
Fate
Study
Reviews
(DERs)
Page:
62
ff
EPA
comment:
(Environmental
fate
DERs
are
included)
Aventis'
response:
The
DERs
should
not
be
included
in
the
RED.
Publication
of
DERs
together
with
the
RED
is
unusual
and
will
put
Aventis
in
a
competitive
disadvantage.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
that
DERs
should
be
made
available
to
the
public
under
the
Freedom
of
Information
Act
after
they
have
been
reviewed
and
cleared
for
confidential
business
information.
EFED
also
wants
to
reduce
the
overall
size
and
level
of
detail
of
its
risk
assessment
for
readability.
EFED
does
not,
however,
take
a
position
regarding
Aventis'
statement
on
"a
competitive
disadvantage"
resulting
from
DER
publication.
71
Appendix
B:
Refined
Water
Memo
Aventis'
response:
This
memo
was
provided
as
an
electronic
copy
and
needs
to
be
inserted
into
the
document.
It
included
text
that
repeated
several
sections
of
the
EFED
document
and
it
included
PRZM
input
tables
for
the
drinking
water
concentrations
using
the
Index
Reservoir
scenario.
It
would
have
been
of
benefit
to
have
the
same
PRZM
inputs
for
the
"standard
pond"
scenarios
that
were
used
to
estimate
surface
water
concentrations
used
in
the
aquatic
risk
assessments.
EFED
Response:
The
full
text
of
the
Refined
Water
Memo
has
been
included
in
Appendix
B
of
the
EFED
chapter.
The
memo
includes
both
PRZM
input
and
output
files.
Appendix
C:
Ecological
Risk
Assessment
Toxicity
Endpoints
Used
in
the
Risk
Assessment
Page:
129
(e
version)
EPA
comment:
Aventis'
response:
Mammalian
acute
oral
LD50
rat
=
307
mg/
kg
The
correct
LD50
is
301
mg/
kg
Mammalian
chronic
(reproduction)
NOAEC
rat
=
80
ppm
Th
e
r
e
s
u
l
t
o
f
t
h
e
recently
submitted
2
generation
rat
study
should
be
used
(75
ppm)
EFED
Response:
As
indicated
previously,
EFED
has
corrected
the
typographical
error
regarding
the
mammalian
acute
oral
LD50
of
301
mg/
kg.
Additionally,
EFED
has
already
commented
regarding
the
recently
submitted
2
generation
rat
study;
even
if
the
study
is
classified
as
acceptable,
the
change
in
NOAEC
from
80
ppm
to
75
ppm
will
not
significantly
affect
the
magnitude
of
the
risk
quotients.
Neither
of
these
changes
have
a
marked
impact
on
EFED's
risk
assessment.
Avian
Acute
and
Chronic
Risk
Page:
130
(e
version)
Paragraph:
1
Line:
1
EPA
comment:
Since
the
avian
LC50
is
greater
than
5,000
ppm
(Appendix
E),
72
Aventis'
response:
The
toxicity
data
are
currently
listed
in
Appendix
D.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
text
has
been
revised
to
read
that
toxicity
data
are
listed
in
Appendix
D.
Page:
132
–
135
(e
version)
EPA
comment:
(Acute
Risk
Quotients
in
Tables
4
and
5,
as
well
as
throughout
the
document
were
a
reference
is
made
to
these
quotients)
Aventis'
response:
As
the
acute
risk
quotients
are
calculated
on
the
basis
of
an
LC50
of
>
5000
ppm,
the
quotients
should
be
given
as
"<
(value)",
not
just
the
value.
The
values
should
also
be
changed
accordingly
throughout
the
document
where
a
reference
is
made
to
these
quotients.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
Appendix
C
Tables
4
and
5
have
been
revised
to
show
that
acute
risk
quotients
are
less
than
the
values
presented.
No
further
changes
were
necessary
in
the
text
since
acute
avian
risk
quotients
were
reported
as
being
less
than
levels
of
concern.
Risk
from
Exposure
to
Non
granular
Products
Page:
137
–
147
(e
version)
EPA
comment:
(Text
and
tables
7
10)
Aventis'
response:
Text
and
tables
should
be
revised.
A
rat
LD50
of
307
mg/
kg
was
used
to
calculate
the
acute
risk
quotients.
The
correct
value
is
301
mg/
kg.
For
calculation
of
the
chronic
risk
quotient
a
NOAEC
of
80
ppm
was
taken
from
a
developmental
study.
The
NOAEC
of
75
ppm
from
a
more
relevant
2
generation
rat
study
recently
submitted
should
be
used
instead.
EFED
Response:
As
noted
previously,
the
mammalian
acute
LD50
value
has
been
corrected
to
301
mg/
kg
and
the
acute
risk
quotients
have
been
revised.
Additionally,
the
chronic
risk
quotients
are
still
based
on
73
a
NOAEC
of
80
ppm.
The
data
from
the
2
generation
rat
study
have
not
been
reviewed;
however,
the
change
in
NOAEC
from
80
to
75
ppm
will
have
no
marked
effect
in
EFED's
risk
assessment.
Risk
from
Exposure
to
Granular
Products
Page:
147
&
148
(e
version)
EPA
comment:
(Text
and
Table
11)
Aventis'
response:
Text
and
tables
should
be
revised.
A
rat
LD50
of
307
mg/
kg
was
used
to
calculate
the
acute
risk
quotients.
The
correct
value
is
301
mg/
kg.
EFED
Response:
As
noted
previously,
references
to
the
rat
LD50
have
been
corrected
to
represent
a
value
of
301
mg/
kg.
Table
11
has
been
corrected.
Aquatic
Plants
Page:
152
(e
version)
EPA
comment:
Based
on
a
single
core
aquatic
plant
toxicity
study
available…
…recommended
that
toxicity
studies
with
Lemna
gibba,
Anabaena
flos
aquae,
Skeletonema
costatum,
and
a
freshwater
diatom
be
submitted.
Aventis'
response:
The
respective
studies
were
submitted
to
the
Agency
in
1992
(see
comments
above
to
Page
2
of
the
Memorandum
for
a
complete
list
and
status).
EFED
Response:
As
noted
previously,
EPA
requires
data
on
5
aquatic
plant
species.
Only
two
of
the
five
species
provided
data
that
were
classified
as
acceptable
and
as
having
fulfilled
guideline
test
requirements.
Therefore,
EFED
is
requesting
that
aquatic
plant
studies
are
repeated
following
EPA
guidelines.
74
Appendix
D:
Toxicity
Assessment
Page:
157
(e
version)
EPA
comment:
Table
1
(spelling
of
author
in
MRID
No.
00160000)
Aventis'
response:
The
author
of
MRID
No.
00160000
should
be
"Hudson
et
al.
".
Also,
it
is
not
obvious
why
the
same
reference
is
one
time
classified
"core"
and
six
times
"supplemental".
The
agency
should
reconsider
if
the
use
of
a
"supplemental"
study
(i.
e.,
rock
dove)
in
calculating
all
acute
RQ
values
is
justified.
EFED
Response:
Table
1
has
been
revised
to
contain
the
correct
spelling
of
the
reference
"Hudson
et
al."
Study
classifications
reported
in
Table
1
are
based
on
whether
recommended
species
were
used
for
testing.
The
only
study
reported
in
Table
to
use
the
recommended
species,
i.
e.,
mallard
ducks,
is
classified
as
core;
the
remaining
studies
did
not
use
recommended
species
and
thus
are
classified
as
supplemental.
Birds,
Chronic
Toxicity
Page:
158
(e
version)
Paragraph:
3
EPA
comment:
Bird
kills
attributed
to
carbaryl
and
involving
blackbirds,
ducks,
starlings,
grackles
turkey,
and
cardinals
have
been
reported
in
Pennsylvania,
Virginia,
New
Jersey,
North
Carolina
and
Michigan
(#
1002048
001,
#1000802
001,
#1007720
020,
##
1000799
003,
#1004375
004).
Aventis'
response:
The
paragraph
should
be
moved
to
the
acute
bird
section.
Also,
only
individuals
familiar
with
this
information
will
recognize
the
numbers
as
the
incident
numbers
from
the
EIIS
database.
An
appropriate
reference
should
be
inserted
here
and
in
similar
citations.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
paragraph
has
been
moved
to
the
discussion
on
acute
avian
toxicity.
Additionally,
a
reference
has
been
inserted
into
the
paragraph
indicating
that
the
information
was
based
on
6(
a)
2
ecological
incident
data.
75
Page:
158
Paragraph:
1
Line:
2
&
3
EPA
comment:
Exposure
to
carbaryl
at
levels
equal
to
or
greater
than
1000
ppm
in
the
mallard
duck
results
in
adverse
reproduction
effects,
such
as
decrease
in
number
of
eggs
produced
include
cracked
eggs,
fertility,
embryonic
mortality,
and
hatching
success.
Aventis'
response:
The
sentence
should
be
changed.
The
embryonic
mortality
and
the
hatching
success
were
not
different
from
the
control.
EFED
Response:
As
stated
previously,
although
the
data
evaluation
record
for
the
avian
reproduction
study
lists
increased
embryonic
mortality
and
reduced
hatching
success
as
significant
effects,
reference
to
these
two
effects
has
been
deleted
from
the
text
since
the
original
study
by
Fletcher
was
not
available
for
secondary
review.
However,
reduced
egg
production,
increased
incidence
of
cracked
eggs
and
decreased
fertility
are
reproductive
effects
that
support
EFED's
concerns
regarding
the
endocrine
disrupting
potential
of
carbaryl.
Mammals,
Acute
and
Chronic
Page:
158
&
159
(e
version)
EPA
comment:
(rat
LD50
of
307
mg/
kg,
NOAEC
80
ppm)
Aventis'
response:
The
acute
LD50
value
for
rat
should
be
corrected
to
301
mg/
kg,
and
the
chronic
NOEAC
to
75
ppm
from
the
2
generation
rat
study.
EFED
Response:
As
noted
previously,
the
mammalian
acute
LD50
value
has
been
corrected
to
301
mg/
kg
and
the
acute
risk
quotients
have
been
revised.
Additionally,
the
chronic
risk
quotients
are
still
based
on
a
NOAEC
of
80
ppm.
Data
from
the
2
generation
rat
study
have
not
been
reviewed;
however,
the
change
in
NOAEC
from
80
to
75
ppm
will
have
no
marked
effect
in
EFED's
risk
assessment.
76
Freshwater
Fish,
Acute
Page:
161
(e
version)
EPA
comment:
Table
6
Aventis'
response:
The
study
classification
of
reference
MRID
40098001
(Mayer
&
Ellersieck,
1986)
should
be
reconsidered
(and
handled
in
a
consistent
fashion).
A
number
of
times
the
reference
is
classified
"core",
while
in
other
instances
the
classification
is
"supplemental".
The
reference
is
an
overview
article
with
little
description
of
test
methods,
analytical
procedures,
GLP,
or
study
details.
The
results
are
generally
listed
in
extensive
tables
(although
summarized
in
the
text
for
some
chemicals).
Such
a
review
article
cannot
be
regarded
as
a
"core"
study
equivalent
to
the
guideline
studies
that
have
to
be
prepared
by
registrants.
Also,
such
studies
with
insufficient
test
method
descriptions
should
not
be
used
in
a
risk
assessment
as
the
primary
source
of
information.
A
submission
based
on
such
data
would
have
certainly
been
rejected
by
the
Agency
EFED
Response:
The
classification
of
Mayer
and
Ellerieck
(1986)
data
reported
in
Table
6
as
either
core
or
supplemental
depends
on
whether
EPA
recommended
species
were
used
for
testing.
Unlike
avian
toxicity
studies
where
only
a
limited
number
of
species
are
recommended
for
testing,
there
is
a
broad
range
of
fish
species
that
EPA
views
as
acceptable
for
testing.
In
Table
6,
chinook
salmon
were
the
only
species
not
recommended
by
EPA
for
testing;
therefore,
the
data
based
on
Chinook
salmon
were
classified
as
supplemental.
The
only
acceptable
data
available
on
technical
grade
carbaryl
other
than
a
study
on
largemouth
bass
by
Johnson
and
Finley
(1980)
were
from
Mayer
and
Ellersieck
(1986).
The
registrant
is
encouraged
to
submit
data
on
the
acute
toxicity
of
technical
grade
carbaryl
to
address
the
uncertainties
that
they
have
identified.
Freshwater
Invertebrates,
Acute
Page:
163
(e
version)
EPA
comment:
Table
9
Aventis'
response:
The
study
classification
of
reference
MRID
40098001
(Mayer
&
Ellersieck,
1986)
should
be
reconsidered
(and
handled
in
a
consistent
fashion).
A
number
of
times
the
reference
is
classified
"core",
while
in
other
instances
the
classification
is
"supplemental".
The
reference
is
a
review
article
with
little
description
of
test
methods,
analytical
procedures,
GLP,
or
77
study
details.
The
results
are
generally
listed
in
extensive
tables
(although
summarized
in
the
text
for
some
chemicals).
Such
an
overview
article
cannot
be
regarded
as
a
"core"
study
equivalent
to
the
guideline
studies
that
have
to
be
prepared
by
registrants.
Also,
such
studies
with
insufficient
test
method
descriptions
should
not
be
used
in
a
risk
assessment
as
the
primary
source
of
information.
EFED
Response:
The
classification
of
Mayer
and
Ellerieck
(1986)
data
reported
in
Table
6
as
either
core
or
supplemental
depends
on
whether
EPA
recommended
species
were
used
for
testing.
As
with
the
freshwater
fish
studies
discussed
previously,
the
registrant
is
encouraged
to
submit
data
on
the
acute
toxicity
of
technical
grade
carbaryl
to
address
the
uncertainties
that
they
have
identified.
Estuarine
and
Marine
Invertebrates,
Acute
Page:
165
(e
version)
EPA
comment:
Table
13,
reference
for
glass
shrimp:
Mayer
&
Ellerersieck
Aventis'
response:
The
reference
should
be
corrected
in
Mayer
&
Ellersieck.
EFED
Response:
EFED
concurs
with
the
registrant's
comments
and
the
reference
in
Table
13
has
been
corrected
to
read
"Mayer
&
Ellersieck
(1986)."
Page:
167
(e
version)
Table
15
EPA
comment:
Table
15,
reference
for
MRID
No.
00265665
Aventis'
response:
The
reference
for
MRID
No.
00265665
should
also
contain
the
citation
of
an
author.
EFED
Response:
The
reference
to
MRID
00265665
(Eastern
oyster
LC50
=
2.5
ppm)
has
been
deleted
from
Table
15.
78
DISCUSSION
EFED
Response:
EFED
has
already
responded
to
all
of
the
issues
discussed
in
this
section.
The
reader
is
referred
to
earlier
responses
to
comments.
1.
Surface
Water
Concentrations
Summary
of
Registrant
Surface
Water/
Drinking
Water
Monitoring
Program
In
section
V,
page
31
EPA
states
that
the
modeling
simulations
provide
a
conservative,
though
not
unreasonable,
estimate
on
possible
concentrations
in
drinking
water.
The
data
from
the
registrant
drinking
water
monitoring
program
provide
the
best
estimate
of
concentrations
of
carbaryl
in
drinking
water.
This
study
uses
the
sampling
design
for
acute
endpoints
recommended
in
industry/
EPA
meetings
during
1999
(weekly
sampling
during
times
of
peak
concentrations
over
a
three
year
period).
Twenty
sites
representing
the
highest
carbaryl
use
areas
were
selected
based
on
the
information
provided
in
Appendix
I.
These
included
16
sites
in
agricultural
areas
and
4
locations
in
urban
areas.
Samples
were
collected
from
the
inlet
and
outlet
water
at
each
sampling
interval.
Outlet
samples
were
only
analyzed
when
residues
were
present
in
the
inlet
samples.
The
analytical
method
had
a
limit
of
quantification
of
0.030
ppb
and
a
limit
of
detection
of
0.002
ppb.
Table
1
summarizes
the
results
of
the
monitoring
at
each
of
the
20
community
water
systems.
The
maximum
concentration
observed
was
0.16
ppb
(average
of
four
samples,
the
highest
was
0.18
ppb)
in
a
finished
water
sample
from
the
Deerfield
community
water
system
located
on
the
River
Raisin
in
Lenawee
County,
Michigan.
There
were
only
five
other
samples
above
the
limit
of
quantification
of
0.030
ppb.
One
was
a
raw
water
sample
containing
0.31
ppb
from
the
Little
Potato
Slough
Mutual
community
water
system
near
Lodi
in
San
Joaquin
County,
California
(the
source
is
the
Little
Potato
Slough).
The
corresponding
finished
water
sample
was
0.007
ppb.
A
second
one
was
a
raw
water
sample
in
Brockton,
MA,
which
contained
0.031
ppb.
No
detectable
residues
were
found
in
the
corresponding
finish
water
sample.
The
last
three
samples
were
from
the
Shades
Mountain
plant
of
the
Birmingham
community
water
system
on
the
Cahaba
River
in
Jefferson
County,
Alabama.
Two
were
raw
and
finished
samples
of
0.038
and
0.032
ppb
at
the
same
sampling
interval
in
2001.
The
other
sample
was
0.035
ppb
in
the
raw
water
in
a
2000
sample
(the
corresponding
finished
sample
did
not
contain
carbaryl
residues.
All
residues
were
transient
so
the
time
weighted
average
concentration
of
carbaryl
in
each
of
the
years
was
0.005
ppb
or
less
at
all
20
community
water
systems.
79
Table
1.
Summary
of
Results
from
the
Carbaryl
Drinking
Water
Monitoring
Study.
Site
Major
Uses
Maximum
Concentration
(ppt)
T
W
A
C
o
n
c
.
(ppt)*
in
Outlet
Water
Inlet
Water
Outlet
Water
1999
2000
2001*
*
1999
2000
2001**
1999
2000
Manatee,
FL
citrus
9
3
ND
11
ND
NA
1
1
West
Sacramento,
orchards,
3
24
ND
3
10
NA
1
1
Lodi,
CA
orchards,
12
31
ND
4
7
NA
1
1
Riverside,
CA
grapes,
tree
8
ND
ND
ND
NA
NA
1
1
Lake
Elsinore,
citrus
ND
3
6
NA
NA
Analysis
1
1
Corona,
CA
citrus
ND
ND
ND
NA
NA
NA
1
1
Beaumont,
TX
various
ND
ND
ND
NA
NA
NA
1
1
Point
Comfort,
rice,
tree
18
5
ND
ND
ND
NA
1
1
Penn
Yan,
NY
grapes,
ND
23
ND
NA
ND
NA
1
1
Westfield,
NY
grapes,
21
5
ND
ND
9
NA
1
1
Jefferson,
OR
vegetables,
ND
10
ND
NA
ND
NA
1
1
Coweta,
OK
pecans
4
ND
***
ND
NA
***
1
1
Pasco,
WA
apples,
2
3
ND
ND
ND
NA
1
1
Manson,
WA
apples
ND
ND
ND
NA
NA
NA
1
1
Deerfield,
MI
vegetables
10
4
ND
160
ND
NA
5
1
Brockton,
MA
cranberries
31
27
ND
ND
3
NA
1
1
East
P
oint,
G
Ahome
a
nd18184
3
8
ND11
Midlothian,
TX
home
and
14
ND
14
ND
NA
ND
1
1
Cary,
NC
home
and
4
ND
ND
ND
NA
NA
1
1
Birmingham,
AL
home
and
23
35
38
ND
ND
32
1
1
*
Annual
Time
Weighted
Concentration,
outlet
values
substituted
for
inlet
values
when
available;
values
below
the
detection
limit
were
considered
to
be
half
the
detection
limit.
**
Results
represent
one
to
six
months
of
sampling
into
the
third
year
program.
***
No
results
available
for
the
third
year
of
sampling.
ND
Not
detected.
NA
No
outlet
samples
analyzed
due
to
carbaryl
residues
not
being
detected
in
inlet
samples.
80
Summary
of
Surface
Water
Data
from
the
NAWQA
Program
In
Section
1
page
3,
Section
4
page
28
and
in
Section
5
page
34,
EPA
has
summarized
the
available
surface
water
monitoring
data
from
the
NAWQA
program
as
having
detections
in
46%
of
the
36
NAWQA
study
units
between
1991
and
1998
with
a
maximum
concentration
of
5.5
ppb.
The
following
tables
summarize
the
carbaryl
analyses
presently
available
from
this
database.
Table
2
is
a
summary
of
the
carbaryl
detections
in
the
updated
database
analysis
recently
reported
by
Larson
(2001).
This
analysis
was
conducted
only
for
samples
collected
during
a
oneyear
period
of
the
most
intensive
sampling
from
each
of
the
sampling
sites.
Numerous
samples
were
excluded
from
this
analysis
as
described
by
Larson:
"A
few
sites
with
sufficient
sampling
for
pesticides
were
excluded
from
the
analysis,
in
order
to
minimize
bias
caused
by
over
representation
of
a
particular
land
use
or
agricultural
setting.
…
The
sampling
requirements
for
a
site
to
be
included
in
the
analysis
were
a
minimum
of
8
samples
collected
in
6
or
more
months
during
the
1
year
period.
In
addition,
samples
must
have
been
collected
during
the
expected
period
of
elevated
pesticide
concentrations.
At
most
of
the
sites
used
in
this
analysis,
20
to
30
samples
were
collected
during
the
selected
1
year
period.…
Not
all
samples
collected
during
the
year
at
each
site
were
used
in
the
calculation
of
the
summary
statistics,
however.
Samples
collected
as
part
of
a
fixed
frequency
sampling
schedule
were
included,
along
with
a
much
smaller
number
of
samples
collected
during
selected
high
or
low
flow
conditions.
Samples
collected
over
a
storm
hydrograph,
or
as
part
of
a
study
of
diurnal
variability,
were
excluded
in
order
to
avoid
bias
resulting
from
repeated
sampling
during
extreme
conditions.
"
Table
2.
Carbaryl
Detections
Reported
in
Pesticides
in
Streams
Update
(Larson,
2001)
Site
Type
Number
of
Number
Carbaryl
Detection
Frequency
(%)
Maximum
All
>=
0.01
>=
0.05
>=
0.10
Agricultural
62
1560
9.2
5.
7
1.8
0.
9
5.2
Urban
Streams
22
611
43
37
19
12
3.2
Integrator
A
31
595
15
11
2.7
1.
2
0.43
A
Large
streams
and
rivers
Results
in
Table
3
and
Table
4
show
a
breakdown
of
all
the
carbaryl
analyses
reported
in
the
USGS
NAWQA
database,
which
was
downloaded
from
their
web
site
July
16,
2001.
The
data
are
reported
separately
for
the
GC/
MS
and
HPLC/
PDA
analyses.
81
Table
3.
Frequency
of
Carbaryl
Detections
by
GC/
MS
in
Different
Concentration
Ranges
Reported
in
the
NAWQA
Database
as
of
July
16,
2001
Land
Use
Number
<=
MDL
C
>0.003
to
>0.01
to
0.1
>0.1
to
1
ppb
>1
ppb
No.
%
No.
%
No.
%
No.
%
No.
%
All
Samples
10379
8388
80.82
617
5.94
1065
10.26
283
2.73
26
0.25
Agricultural
4349
3888
89.40
188
4.32
225
5.17
46
1.06
2
0.
05
Urban
1763
921
52.24
161
9.13
463
26.26
195
11.06
23
1.30
Mixed
A
3648
3022
82.84
247
6.77
345
9.46
33
0.90
1
0.
03
Other
B
619
557
89.98
21
3.39
32
5.17
9
1.
45
0
0
A
Large
streams
and
rivers.
Includes
all
of
the
"Integrator"
sites
listed
in
Larson,
et
al.
.,
1999
and
many
more.
B
Includes
forest,
rangeland,
mining,
etc.
C
The
method
detection
limit
(MDL)
for
carbaryl
analyzed
by
the
GC/
MS
method
is
0.003
:
g/
L,
but
updated
MDLs
presented
in
the
database
may
be
higher
for
some
analyses
and
are
included
in
this
category.
Table
4.
Frequency
of
Carbaryl
Detections
by
LC/
PDA
in
Different
Concentration
Ranges
Reported
in
the
NAWQA
Database
as
of
July
16,
2001
Land
Use
Number
<=
MDL
C
>0.008
to
>0.01
to
0.1
>0.1
to
1
ppb
>1
ppb
No.
%
No.
%
No.
%
No.
%
No.
%
All
Types
5516
5348
96.
95
9
0.16
93
1.69
54
0.98
12
0.22
Agricultural
2528
2509
99.
25
1
0.
04
13
0.
51
3
0.12
2
0.
08
Urban
1189
1064
89.
49
4
0.34
64
5.38
47
3.95
10
0.84
Mixed
A
1523
1501
98.
56
4
0.
26
15
0.
98
3
0.2
0
0
Other
B
27627499.
280
0
1
0.
3610.
360
0
A
Large
streams
and
rivers.
Includes
all
of
the
"Integrator"
sites
listed
in
Larson,
et
al.
.,
1999
and
many
more.
B
Includes
forest,
rangeland,
mining,
etc.
C
The
method
detection
limit
(MDL)
for
carbaryl
analyzed
by
the
LC/
PDA
method
is
0.008
:
g/
L,
but
updated
MDLs
presented
in
the
database
may
be
higher
for
some
analyses
and
are
included
in
this
category.
Summary
of
Carbaryl
Analytical
Methods
used
in
the
NAWQA
Program
In
a
number
of
instances
throughout
their
review,
EPA
has
made
reference
to
the
"poor
recovery"
for
carbaryl
noted
in
a
NAWQA
summary
document
(Larson,
1999).
In
this
document,
reference
is
made
to
mean
percent
recovery
of
24%
for
carbaryl
with
a
method
detection
limit
(MDL)
of
0.003
ppb.
The
Agency
cites
this
low
mean
recovery
several
times
as
evidence
that
the
concentrations
of
carbaryl
reported
in
the
database
widely
underestimate
the
actual
concentrations
of
carbaryl
in
the
water
samples.
This
claim
is
misleading
and
should
be
removed
from
each
location
in
the
draft
RED
for
reasons
discussed
below.
Two
analytical
methods
were
developed
as
part
of
the
NAWQA
program
and
both
of
them
have
been
used
in
the
analysis
of
carbaryl.
The
first
method,
used
for
a
majority
of
the
NAWQA
data
reported
for
carbaryl,
is
a
GC/
MS
method
with
an
MDL
of
0.003
ppb
(Zaugg,
et
al.,
1995).
The
second
method,
used
for
a
limited
number
of
samples
in
which
carbaryl
was
analyzed,
is
an
82
LC/
Photodiode
Array
(PDA)
method
with
an
MDL
of
0.008
ppb
(Werner
et
al.
.,
1996).
In
the
NAWQA
database
the
quantitative
data
for
carbaryl
determined
by
the
GC/
MS
method
are
flagged
with
an
"E",
as
are
data
for
several
other
analytes,
indicating
that
the
analysts
have
noted
"the
potential
for
variable
performance"
in
the
analysis
of
carbaryl.
None
of
the
carbaryl
data
in
the
NAWQA
database
has
been
corrected
for
procedural
recoveries
that
were
noted
in
the
documents
described
above.
Both
of
these
methods
are
discussed
below
in
relation
to
the
recoveries
found
for
the
methods
and
the
potential
impact
this
could
have
on
the
analytical
data
for
carbaryl.
Gas
Chromatography/
Mass
Spectroscopy
Method
The
analytical
method
most
used
in
the
NAWQA
program
for
the
analysis
of
carbaryl
in
water
samples
is
the
GC/
MS
method
described
by
Zaugg,
et
al.,
1995.
In
this
multi
residue
method,
the
analytes
are
first
removed
from
the
water
sample
by
sorption
on
a
C
18
solid
phase
and
are
subsequently
eluted
from
the
solid
phase,
separated
by
GC
and
quantified
by
mass
spectroscopy
with
selected
ion
monitoring.
The
identity
of
each
analyte
is
confirmed
by
the
appropriate
combination
of
retention
time
and
the
ratios
of
three
mass
ions
that
are
characteristic
for
the
analyte.
The
recoveries
for
carbaryl
spiked
at
different
levels
into
three
different
types
of
water
and
analyzed
by
the
GC/
MS
method
are
shown
in
Table
5
Mean
percent
recoveries
of
151
and
202%
were
found
for
carbaryl
fortified
at
0.1
and
1.0
:
g/
L
in
reagent
grade
water.
A
preliminary
MDL
of
0.046
:
g/
L
was
calculated
for
the
0.1
:
g/
L
spiking
level.
Mean
percent
recoveries
of
10
and
75%
were
found
for
carbaryl
fortified
at
0.1
and
1.0
:
g/
L
in
a
surface
water
sample
collected
from
the
South
Platte
River.
However,
carbaryl
was
detected
at
0.18
:
g/
L
in
this
water,
or
nearly
twice
the
low
spike
level,
raising
questions
about
the
validity
of
this
result.
Mean
percent
recoveries
of
94
and
86%
were
found
for
carbaryl
fortified
at
0.1
and
1.0
:
g/
L
in
a
ground
water
sample
collected
from
a
well
in
Denver.
A
mean
recovery
value
of
24%
was
reported
for
reagent
grade
water
fortified
at
a
level
of
0.03
:
g/
L
with
a
method
detection
limit
calculated
at
0.003
:
g/
L.
Table
5.
Recovery
and
Precision
for
Multiple
Determinations
of
Carbaryl
in
GC/
MS
Method
for
Carbaryl
Spiked
in
Different
Water
Samples
Water
type
Spike
Concentration
Mean
Recovery
(%)
MDL
Calculated
Reagent
Grade
0.
1
151
0.046
Reagent
Grade
1.
0
202
Surface
A
0.1
10
Surface
A
1.0
75
Ground
B
0.1
94
Ground
B
1.0
86
Reagent
Grade
0.
03
24
0.
003
A
Surface
water
was
collected
from
the
South
Platte
River
near
Henderson,
Colorado.
This
water
was
found
to
contain
significant
concentrations
of
several
pesticides
including
0.18
:
g/
L
carbaryl.
This
concentration
was
subtracted
from
the
values
determined
to
give
corrected
results.
B
Ground
water
was
collected
from
the
Denver
Federal
Center
Well
15.
83
Whereas
the
values
reported
by
Zaugg,
et
al.
(1995)
are
of
interest
in
validating
the
analytical
method,
they
are
not
as
useful
in
evaluating
the
validity
of
the
data
contained
in
the
NAWQA
database.
Therefore,
quoting
the
mean
recovery
value
of
24%
for
reagent
grade
water
spiked
with
carbaryl
at
0.03
:
g/
L
as
evidence
that
the
concentrations
reported
in
the
database
underestimate
the
actual
concentrations
of
carbaryl
present
in
the
water
samples
is
misleading.
A
more
useful
measure
of
the
validity
of
the
values
in
the
database
lies
with
the
quality
control
checks
that
have
been
incorporated
into
the
analysis
of
samples
in
the
NAWQA
program.
In
a
preliminary
report,
Martin
(1999)
reported
the
quality
control
data
collected
as
part
of
the
NAWQA
surface
and
ground
water
programs
by
the
1991
NAWQA
Study
Unit
teams
or
the
National
Water
Quality
Laboratory
(NWQL)
during
1992
to
1996.
The
data
that
were
compiled
includes
field
blanks,
laboratory
control
spikes
and
field
matrix
spikes,
which
are
defined
below
by
Martin.
"Field
blanks
were
collected
at
the
field
site
with
pesticide
grade
blank
water
and
are
exposed
to
the
field
and
laboratory
environments
and
equipment
similarly
to
environmental
samples.
Field
blanks
measure
the
frequency
and
magnitude
of
contamination
(one
type
of
positive
bias)
in
environmental
water
samples
from
sources
in
the
field
and/
or
laboratory.
Contamination
is
the
main
cause
of
falsepositive
detections
(detecting
a
pesticide
in
a
sample
when,
in
truth,
it
is
absent)."
"Laboratory
control
spikes
measure
the
bias
and
variability
of
the
analytical
method
at
a
particular
concentration.
One
laboratory
control
spike
is
measured
in
each
analytical
set
of
environmental
samples.
The
laboratory
control
spike
has
the
target
pesticides
spiked
into
pesticide
grade
blank
water
at
the
laboratory
and
extracted,
processed,
and
analyzed
like
environmental
samples.
Laboratory
control
spikes
analyzed
by
GCMS
were
spiked
at
0.1
µg/
L…"
"Field
matrix
spikes
measure
the
bias
and
variability
of
the
analytical
method
PLUS
any
potential
effects
caused
by
(1)
degradation
of
pesticides
during
shipment
to
the
laboratory,
(2)
inferences
in
the
determination
of
pesticides
from
unusual
characteristics
of
the
environmental
water
sample
("
matrix
effects"),
and
(3)
other
chemical
processes
that
cause
bias
or
variability
in
the
measurements
of
pesticides
in
environmental
water
samples.
Field
matrix
spikes
analyzed
by
GCMS
were
spiked
at
0.1
µg/
L,…"
All
of
the
carbaryl
analyses
in
the
field
blanks,
field
matrix
spikes
and
lab
control
spikes
were
conducted
following
the
same
method
described
by
Zaugg
et
al.,
1995
that
was
used
to
generate
a
majority
of
the
carbaryl
data
contained
in
the
NAWQA
database.
The
data
below
were
excerpted
from
Tables
1
to
4
of
the
Martin
report.
Carbaryl
is
found
in
these
tables
under
parameter
82680.
Out
of
145
samples
taken
as
ground
water
field
blanks,
carbaryl
was
not
detected
in
any
of
the
samples
indicating
a
lack
of
false
positives.
Out
of
171
samples
taken
as
surface
water
field
84
blanks,
carbaryl
was
reported
in
two
samples
(1.2%
false
positives)
at
reported
concentrations
of
0.009
and
0.012
:
g/
L.
A
summary
of
the
results
for
the
field
matrix
spikes
and
the
lab
control
spikes
is
presented
in
Table
6
Mean
recovery
for
the
306
field
matrix
spikes
was
115%
of
the
spiking
level
of
0.1
:
g/
L
with
a
median
recovery
of
94.4%
and
a
90
th
percentile
recovery
of
200%.
This
indicates
the
potential
for
the
method
to
over
estimate
the
concentration
of
carbaryl
present
in
the
water
samples
and
is
consistent
with
the
initial
data
reported
for
the
reagent
water
samples
by
Zaugg
et
al.
(1995).
Mean
recovery
for
the
1000
lab
control
spikes
was
99.6%
of
the
spiking
level
of
0.1
:
g/
L
with
a
median
recovery
of
93%
and
a
90
th
percentile
recovery
of
185%.
These
data
suggest
an
adequate
level
of
detection
of
carbaryl
in
QC
samples
that
were
analyzed
as
part
of
the
same
process
used
in
the
NAWQA
survey
of
pesticides
in
surface
and
ground
water.
85
Table
6.
Percent
Recoveries
of
Carbaryl
Detected
by
the
NAWQA
GC/
MS
Method
in
Laboratory
Control
Spikes
and
Field
Matrix
Spikes
at
a
Spiking
level
of
0.1
:
g/
L
Sample
Type
Number
of
10
th
Median
Mean
90
th
Maximum
Field
Matrix
Spike
306
40
94.4
115.0
199.9
456
Laboratory
Control
1000
20
93.0
99.6
185.1
329
The
following
disclaimer
was
taken
verbatim
from
the
provisional
report
by
Martin
(1999)
and
pertains
to
the
data
provided
above
on
the
recovery
of
carbaryl
in
the
field
matrix
spike
samples.
"The
field
matrix
spike
data
have
not
been
reviewed
thoroughly,
are
provisional,
and
are
subject
to
change.
Further
review
of
the
field
spike
data
is
expected
to
identify
spikes
that
have
extremely
high
or
low
recoveries
because
the
spikes
either
were
improperly
collected
or
incorrectly
documented
in
the
NAWQA
QC
data
base.
The
expected
result
of
further
review
is
a
data
set
of
field
matrix
spikes
with
fewer
extreme
values
than
the
provisional
data
set
described
in
this
paper;
consequently,
the
provisional
data
set
provides
a
conservative
estimate
of
the
quality
of
the
NAWQA
pesticide
data.
Interpretations
of
field
matrix
spike
data
in
this
paper
are
not
expected
to
change
greatly
as
a
result
of
further
review
of
the
data,
however,
the
statistics
and
confidence
limits
reported
in
the
text
and
tables
will
change
on
further
review
(especially
for
pesticides
with
low
numbers
of
field
spikes
[less
than
50])."
High
Performance
Liquid
Chromatography/
Photodiode
Array
Method
Another
analytical
method
used
in
the
NAWQA
program
for
the
analysis
of
carbaryl
in
water
samples
is
the
LC/
PDA
method
described
by
Werner,
et
al.,
1996.
This
method
was
used
for
the
analysis
of
carbaryl
in
a
limited
number
of
samples
as
noted
above.
In
this
multi
residue
method,
the
analytes
are
first
removed
from
the
water
sample
by
sorption
on
a
Carbopak
B
solid
phase
extraction
cartridge
and
are
subsequently
eluted
from
the
solid
phase,
separated
by
HPLC
and
quantified
by
light
absorption
using
a
photodiode
array
detector.
The
identity
of
each
analyte
is
confirmed
by
the
appropriate
combination
of
retention
time
and
light
absorption
characteristics.
The
recoveries
for
carbaryl
spiked
at
different
levels
into
three
water
samples
and
analyzed
by
this
method
is
shown
in
Table
7
The
recoveries
ranged
from
58%
to
84%
for
the
different
water
and
spiking
levels.
Laboratory
control
spikes
in
organic
free
water
resulted
in
a
mean
recovery
of
61%
over
a
two
year
sampling
period.
These
results
indicate
reasonable
levels
of
carbaryl
recovery
from
each
of
the
different
types
of
water
evaluated
for
the
method.
86
Table
7.
Recovery
and
Precision
for
Multiple
Determinations
of
Carbaryl
in
LC/
PDA
Method
for
Carbaryl
Spiked
in
Different
Water
Samples
Water
type
Spike
Concentration
Mean
Recovery
(%)
MDL
Calculated
Organic
Free
0.1
82
0.
008
Organic
Free
1.0
70
Surface
A
0.1
84
0.
016
Surface
A
1.0
84
Ground
B
0.1
58
0.
018
Ground
B
1.0
64
Organic
Free
0.5
61
C
A
Surface
water
was
collected
from
the
South
Platte
River
at
Englewood,
Colorado.
B
Ground
water
was
collected
from
Jefferson
County,
Colorado
(Arvada
Well
14).
C
National
Water
Quality
Laboratory
results
produced
using
5
operators
and
7
instruments
over
2
years
(about
350
data
points).
Summary
of
Surface
Water
Data
from
the
California
DPR
Surface
Water
Database
In
Section
5
pages
34
to
37
EPA
has
summarized
surface
water
monitoring
data
from
various
sources.
One
source
not
included
in
this
discussion
is
the
California
Surface
Water
Monitoring
Database.
The
number
of
analyses
and
the
detections
of
carbaryl
residues
reported
in
the
database
are
summarized
in
Table
8.
Carbaryl
was
detected
at
levels
above
the
LOQ
in
only
5.1%
of
the
2,690
samples
analyzed.
The
mean
concentration
of
carbaryl
in
the
140
samples
above
the
LOQ
was
0.42
ppb.
The
highest
concentration
of
carbaryl
that
was
detected
was
8.4
ppb.
An
analysis
of
the
data
in
the
California
Department
of
Pesticide
Regulation's
surface
water
database
as
of
July
15,
2000
was
conducted
for
carbaryl.
The
following
summary
of
the
contents
of
the
database
is
adapted
from
information
provided
by
the
California
DPR.
The
database
contains
monitoring
results
for
pesticides
in
samples
taken
from
California
rivers,
creeks,
urban
streams,
agricultural
drains,
the
Delta,
and
urban
stormwater
runoff.
As
of
July
15,
2000,
the
database
contained
the
results
of
30
studies
conducted
by
federal,
state,
and
local
agencies,
private
industry,
and
an
environmental
group.
A
total
of
4,660
samples
were
taken
in
16
counties
from
January
1991
through
March
2000.
Each
record
in
the
database
is
the
result
of
one
analysis
for
a
pesticide
active
ingredient
or
breakdown
product.
The
database
contains
a
total
of
92,296
analytical
records.
Only
information
on
the
analytical
detection
of
carbaryl
in
these
water
samples
is
summarized
in
Table
8
below.
Table
8.
Carbaryl
Detections
Reported
in
California
DPR
Surface
Water
Monitoring
Database
Land
Use
Number
<=
LOQ
>0.003
to
>0.01
to
0.1
>0.1
to
1
ppb
>1
ppb
No.
%
No.
%
No.
%
No.
%
No.
%
All
Samples
2690
2553
94.91
13
0.48
55
2.04
55
2.04
14
0.52
Concentrations
of
analytical
results
that
are
reported
below
the
limit
of
quantification
are
reported
as
a
zero
in
the
database
concentration
field.
The
LOQs
for
the
different
methods
used
to
generate
the
data
contained
in
the
database
ranged
from
0.003
to
0.5
:
g/
L,
with
a
majority
of
the
samples
analyzed
with
an
LOQ
of
0.05
:
g/
L
or
less
(Table
9)
.
87
Table
9.
Limits
of
Quantification
for
Carbaryl
Analytical
Methods
Reported
in
California
DPR
Surface
Water
Monitoring
Database
LOQ
(
:
g/
L)
0.003
0.041
0.044
0.05
0.07
0.1
0.
5
Number
of
267
238
168
1353
92
53
146
88
2.
Ground
Water
Concentrations
In
Section
5
page
34
EPA
summarized
information
on
the
detection
of
carbaryl
in
groundwater
from
the
EPA
Pesticides
in
Groundwater
Database,
the
EPA
STORET
database
and
the
NAWQA
database.
Each
of
the
databases
shows
a
pattern
of
very
low
levels
of
carbaryl
detection
in
few
groundwater
resources.
These
analyses
confirm
several
statements
made
by
the
Agency
that
carbaryl
has
limited
potential
to
impact
groundwater
resources.
However,
on
page
2
of
the
Memorandum
issued
June
28,
2001,
in
conjunction
with
the
EFED
RED
chapter
for
carbaryl,
EPA
is
requiring
additional
information
on
"Surface
and
groundwater
monitoring
in
urban
and
suburban
use
areas
(non
guideline)."
Based
on
the
characteristics
of
carbaryl
and
the
available
data
demonstrating
limited
impact
of
carbaryl
on
ground
water
resources,
additional
studies
to
evaluate
the
potential
for
carbaryl
to
contaminate
groundwater
are
unnecessary
and
unwarranted.
Summary
of
Ground
Water
Data
from
the
NAWQA
Program
In
Section
5,
pages
33
34,
EPA
has
summarized
ground
water
monitoring
data
available
for
carbaryl.
The
database
that
contains
the
most
extensive
evaluation
of
the
impact
of
the
most
recent
uses
of
carbaryl
on
ground
water
is
the
NAWQA
database.
One
deficiency
of
the
NAWQA
program
is
that
samples
are
targeted
to
agricultural
and
urban
areas
but
not
to
areas
treated
with
the
specific
chemical
being
analyzed.
However,
given
the
use
patterns
of
carbaryl,
the
use
of
carbaryl
has
certainly
occurred
near
a
number
of
these
wells.
Another
deficiency
is
that
when
residues
are
found,
that
while
they
may
be
representative
of
residues
in
ground
water,
they
may
not
be
representative
of
residues
in
ground
water
used
for
drinking
water
due
to
the
location
of
the
sampled
wells
relative
to
potable
drinking
water
wells.
EPA
cited
a
1998
review
of
the
NAWQA
database
by
Kolpin
and
stated:
"Carbaryl
was
detected
at
greater
than
the
detection
limit
(0.003
µg/
L)
in
1.1
%
of
groundwater
samples
from
1034
sites
across
the
U.
S.
by
U.
S.
G.
S.
NAQWA
(sic)
program.
The
maximum
observed
concentration
was
0.021
µg/
L."
This
1998
analysis
has
been
extended
by
additional
study
data
collected
by
the
NAWQA
program.
The
additional
data
continue
to
show
a
limited
number
of
low
level
detections
of
carbaryl
in
ground
water
samples.
Table
10
below
summarizes
a
more
recent
provisional
review
by
Kolpin
(2001)
of
the
updated
NAWQA
database.
Not
all
of
the
water
samples
were
used
to
calculate
the
summary
statistics
as
noted
by
Kolpin:
"To
preclude
bias
in
these
summary
statistics
from
wells
that
were
sampled
more
than
once,
the
data
set
was
condensed
such
that
each
well
had
a
single
pesticide
analysis.
This
generally
was
the
first
sample
collected.
However,
subsequent
samples
were
selected
if
these
samples
contained
more
pesticide
data
(i.
e.,
a
larger
number
of
pesticides
were
analyzed).
Wells
that
were
designed
to
be
a
part
of
both
a
land
use
study
and
a
major
aquifer
survey
were
used
in
each
summary.
Because
of
89
uncertainties
in
the
source
of
water
and
contributing
land
use
area,
springs
and
drains
were
excluded
from
these
summaries."
Table
10.
Carbaryl
Detections
Reported
in
Pesticides
in
Ground
Water
Update
(Kolpin,
2001)
Site
Type
Number
Carbaryl
Detection
Frequency
(%)
Maximum
All
>=
0.01
>=
0.05
>=
0.10
Agricultural
Land
1244
0.40
0.16
0.0
0.
0
0.019
Urban
Land
Use
634
2.1
1.
3
0.0
0.
0
0.031
Major
Aquifers
1849
0.59
0.54
0.05
0.05
0.539
90
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T.
Novak
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1996.
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W.
D.,
D.
F.
Berry,
A.
Bhandair,
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J.
T.
Novak.
1999.
Impact
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Soil
Chemical
Interactions
on
the
Bioavailability
of
Naphthalene
and
1
Naphthol.
Water
Research,
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Hassett,
J.
J.,
W.
L.
Banwart,
S.
G.
Wood,
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C.
Means.
1981.
Sorption
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naphthol:
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the
limits
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Soil
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Soc.
Am.
J
45(
1):
38
42.
Kolpin,
D.
W.
June
11,
2001.
Pesticides
in
Ground
Water,
Summary
statistics;
Results
of
the
National
Water
Quality
Assessment
Program
(NAWQA),
1992
1998.
Available
for
download
from
http://
water.
wr.
usgs.
gov/
pnsp/
pestgw/.
Larson,
S.
J.
June
11,
2001.
Pesticides
in
Streams,
Summary
statistics;
Results
of
the
National
Water
Quality
Assessment
Program
(NAWQA),
1992
1998.
Available
for
download
from
http://
water.
wr.
usgs.
gov/
pnsp/
pestsw/.
Martin,
J.
D.
October
27,
1999
.Quality
of
Pesticide
Data
for
Environmental
Water
Samples
Collected
for
the
National
Water
Quality
Assessment
Program,
1992
96
and
Examples
of
the
Use
of
Quality
Control
Information
in
Water
Quality
Assessments.
Available
for
review
at:
http://
water.
wr.
usgs.
gov/
pnsp/
rep/
qcsummary/
McCall,
P.,
D.
Laskowski,
R.
Swann,
and
H.
Dishburger.
1980.
Measurement
of
Sorption
Coefficients
of
Organic
Chemicals
and
Their
Use
in
Environmental
Fate
Analysis.
In:
Test
Protocols
for
Environmental
Fate
&
Movement
of
Toxicants.
Proceedings
of
a
Symposium,
Association
of
Official
Analytical
Chemists,
94th
Annual
Meeting,
October
21,
22,
1980.
pp
89
109.
Werner,
I.,
L.
A.
Denovic,
V.
Conner,
V.
De
Vlaming,
H.
Bailey
and
D.
E.
Hinton.
2000.
InsecticideCaused
Toxicity
to
Ceriodaphnia
dubia
(Cladocera)
in
the
Sacramento
San
Joaquin
River
Delta,
California.
Environmental
Toxicology
and
Chemistry,
19:
215
227.
Werner,
S.
L.,
M.
R.
Burkhardt
and
S.
N.
DeRusseau.
1996.
METHODS
OF
ANALYSIS
BY
THE
U
.S.
GEOLOGICAL
SURVEY
NATIONAL
WATER
QUAL
I
T
Y
LABORATORY—
DETERMINATION
OF
PESTICIDES
IN
WATER
BY
CARBOPAK
B
SOLIDPHASE
EXTRACTION
AND
HIGH
PERFORMANCE
LIQUID
CHROMATOGRAPHY.
U.
S.
Geological
Survey
Open
File
Report
96
216,
42
pp.
Available
for
download
from
http://
wwwnwql.
cr.
usgs.
gov/
Public/
pubs/
OFR96
216/
OFR96
216.
html.
91
Zaugg,
S.
D.,
M.
W.
Sandstrom,
S.
G.
Smith
and
K.
M.
Fehlberg.
1995.
METHODS
OF
ANALYSIS
BY
THE
U.
S.
GEOLOGICAL
SURVEY
NATIONAL
WATER
QUALITY
LABORATORY—
DETERMINATION
OF
PESTICIDES
IN
WATER
BY
C
18
SOLID
PHASE
EXTRACTION
AND
CAPILLARY
COLUMN
GAS
CHROMATOGRAPHY/
MASS
SPECTROMETRY
WITH
SELECTED
ION
MONITORING.
U.
S.
Geological
Survey
Open
File
R
e
p
o
r
t
9
5
1
8
1
,
4
9
p
p
.
A
v
a
i
l
a
b
l
e
f
o
r
d
o
w
n
l
o
a
d
f
r
o
m
http://
wwwnwql.
cr.
usgs.
gov/
Public/
pubs/
OFR95
181/
OFR95
181.
html.
92
Confidential
Business
Attachment
APPENDIX
1
Surface
Water
Monitoring
for
Residues
of
Carbaryl
in
High
Use
Areas
of
the
United
States
(Stone
Environmental,
Inc.
Report
#99
1005
F)
(hard
copy
provided).
93
Confidential
Business
Attachment
APPENDIX
2
Calculation
of
County
Average
Carbaryl
Use
Rates
(hard
copy
provided)
| epa | 2024-06-07T20:31:42.505005 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0018/content.txt"
} |
EPA-HQ-OPP-2002-0138-0019 | Supporting & Related Material | "2002-07-31T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
CERTIFIED
MAIL
June
25,
2002
Danielle
LaRochelle
Registration
Product
Manager
Aventis
CropScience
USA
P.
O.
Box
12014
2
T.
W.
Alexander
Drive
Research
Triangle
Park,
NC
27709
Re:
Second
Error
Correction
of
Carbaryl
Risk
Assessments
Dear
Ms.
LaRochelle:
Within
two
weeks
from
the
date
of
this
letter,
please
identify
and
comment
on
any
errors
in
the
enclosed
risk
assessment
documents
for
carbaryl,
addressing
only
typographic,
mathematical,
or
computational
type
errors.
The
enclosed
documents
include
the
human
health
and
the
environmental
fate
and
effects
risk
assessments.
Also
enclosed
for
your
reference
are
supporting
documents
for
the
human
health
risk
assessment.
Last
August,
Aventis
completed
its
first
error
correction
review
of
these
documents.
As
a
courtesy,
EPA
is
offering
Aventis
a
second
error
correction
review
of
these
documents
because
of
substantive
changes
described
later
in
this
letter.
On
receiving
your
error
correction
submission,
the
Agency
will
evaluate
your
comments
and
will
revise
the
risk
assessments
as
necessary.
At
this
phase,
EPA
will
not
address
comments
concerning
matters
of
policy,
interpretation,
or
applicability
of
data.
Aventis
will
have
ample
opportunity
to
submit
such
comments
during
the
60
day
public
comment
period
that
will
begin
in
the
next
few
weeks.
As
part
of
your
two
week
review,
please
also
inform
the
Agency
in
writing
of
any
claims
of
confidential
business
information
(CBI)
contained
in
these
documents.
If
we
do
not
receive
notice
in
writing
of
any
such
claims
within
the
two
weeks,
we
will
assume
the
document
is
free
of
CBI.
Please
send,
in
writing,
the
results
of
your
error
correction
and
CBI
review
to:
Anthony
Britten
US
EPA
(7508C)
1200
Pennsylvania
Avenue,
N.
W.
Washington,
D.
C.
20460
E
mail
Address:
britten.
anthony@
epa.
gov
Fax:
(703)
308
8005
2
Background
EPA
is
offering
this
second
courtesy
error
review
because
of
substantive
changes
to
the
risk
assessments.
These
changes
were
prompted
by
new
data
Aventis
submitted
since
its
first
error
correction
review.
The
new
data
includes
a
two
generation
rat
reproduction
study,
data
from
a
developmental
neurotoxicity
study,
and
three
dermal
studies.
EPA
also
rereviewed
carbaryl
under
the
latest
cancer
assessment
guidelines.
The
two
weeks
offered
for
this
error
review
coincides
with
the
time
necessary
to
publish
the
Federal
Register
notice
announcing
the
start
of
the
Phase
3
public
comment
period.
The
publication
process
is
now
underway.
Two
weeks
is
also
the
period
EPA
usually
offers
for
a
second
review
of
typographic,
mathematical
or
computational
type
errors.
As
part
of
its
Phase
1
error
review,
Aventis
submitted
substantive
comments
to
the
Agency.
EPA
generally
does
not
consider
substantive
comments
received
during
Phase
1.
However,
in
this
case,
EPA
considered
the
comments
while
awaiting
and
then
analyzing
the
new
data
from
Aventis.
EPA
will
specifically
respond
to
these
comments
in
a
document
prepared
at
the
end
of
phase
3.
You
need
not
resubmit
your
substantive
comments.
Please
keep
your
review
in
the
next
two
weeks
focused
solely
on
typographic,
mathematical
or
computational
type
errors.
Again,
Aventis
will
also
have
the
full
60
days
of
Phase
3
to
submit
further
substantive
comments,
which
EPA
will
address
in
its
next
revision
of
the
risk
assessments.
The
appropriate
level
of
detail
for
your
error
response
would
be
the
amount
of
information
that
would
fit
in
the
margins
of
a
pen
and
ink
markup.
In
fact,
a
pen
and
ink
markup
would
be
the
preferred
response.
Please
complete
your
review
of
the
comprehensive
risk
assessments
before
focusing
attention
on
the
supporting
documents.
Prioritizing
your
review
in
this
way
will
help
ensure
the
most
significant
corrections
are
made
in
a
timely
way.
Sending
corrections
"piecemeal"
is
also
recommended.
Adopting
these
standards
of
review
should
allow
both
Aventis
and
EPA
enough
time
to
correct
the
enclosed
documents
before
their
release
for
Phase
3
public
comment.
If
you
have
questions
about
this
request,
please
contact
Anthony
Britten,
the
Chemical
Review
Manager
for
carbaryl,
at
(703)
308
8179.
Sincerely,
//
signed
by
Anthony
Britten
for//
Betty
Shackleford,
Acting
Associate
Director
Special
Review
and
Reregistration
Division
Enclosures
| epa | 2024-06-07T20:31:42.533337 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0019/content.txt"
} |
EPA-HQ-OPP-2002-0138-0020 | Supporting & Related Material | "2002-07-31T04:00:00" | null | July
18,
2002
Mr.
Anthony
Britten,
SRRD
Document
Processing
Desk
(7504C)
Office
of
Pesticide
Programs
U.
S.
Environmental
Protection
Agency
Room
266A,
Crystal
Mall
2
1921
Jefferson
Davis
Highway
Arlington,
Virginia
22202
Dear
Mr.
Britten,
Re:
Carbaryl;
Chemical
number
56801;
EPA
Reg.
No.
264
324
Error
Correction
of
Carbaryl
Risk
Assessments
Attached
are
our
comments
on
the
error
correction
review
of
the
revised
HED
and
EFED
Risk
Assessments
for
Carbaryl.
We
have
also
included
some
comments
on
certain
supporting
documents
for
the
HED
Chapter.
One
issue
of
concern
was
noted
during
our
review
of
the
risk
assessments.
It
appears
that
the
Agency
intends
to
include
the
Data
Evaluation
Records
(DERs)
for
a
number
of
carbaryl
studies
in
the
draft
EFED
Chapter
which
will
be
made
available
to
the
public
for
the
60
day
comment
period.
We
believe
that
it
is
inappropriate
to
include
the
DERs
in
the
RED
document.
A
sufficiently
detailed
summary
of
study
findings
is
already
provided
in
the
EFED
Chapter.
The
summary
of
endpoints
that
is
included
in
the
draft
Carbaryl
EFED
Chapter
is
typical
of
other
Draft
EFED
REDs
that
have
been
issued
recently
and
provides
sufficient
information
to
allow
the
reader
to
determine
the
endpoints
that
were
selected
for
modeling
and
the
justification
for
their
selection.
The
inclusion
of
the
more
detailed
information
present
in
the
DERs
is
unnecessary.
We
have
reviewed
the
dockets
for
many
of
the
RED
documents
that
have
recently
been
issued
(many
other
insecticides
and
several
fungicides)
and
none
of
them
include
DERs
in
any
of
the
preliminary
Environmental
Fate
and
Effects
Assessments.
DERs
should
be
made
available
to
the
public
through
the
regular
procedure
under
the
Freedom
of
Information
Act
after
they
have
been
reviewed
and
cleared
for
confidential
business
information.
The
inclusion
of
the
DERs
in
the
docket
that
is
publicly
available
circumvents
this
process
and
is
a
departure
from
the
procedures
that
have
been
followed
until
now
by
the
Agency.
It
is
unclear
why
the
Agency
chose
to
change
their
policy
for
only
certain
DERs
for
a
single
product
when
adequate
summary
information
is
already
provided
in
the
text
of
the
Carbaryl
EFED
Chapter.
This
issue
deserves
careful
consideration
before
the
Agency
makes
the
decision
to
amend
their
existing
policy
on
providing
this
type
of
information
to
the
public.
Your
help
in
ensuring
that
July
12,
2002
Mr.
Anthony
Britten
Page
2
of
2
accepted
procedures
are
followed
for
the
public
review
of
the
Carbaryl
RED
Chapters
is
greatly
appreciated.
Sincerely,
Danielle
A.
Larochelle
Registration
Manager
Corr.
#
daL018
02
CARBARYL
PC
Code
No.
056801;
Case
0080
Human
Health
Risk
Assessment
and
Supporting
Documents
–
Phase
1
Error
Correction
–
July
12,
2002
Aventis
CropScience
P.
O.
Box
12014,
2
T.
W.
Alexander
Drive
Research
Triangle
Park,
NC
27709
CARBARYL
Human
Health
Risk
Assessment
and
Supporting
Documents
Phase
1
Error
Correction
TABLE
OF
CONTENTS
TABLE
OF
CONTENTS
................................................................................................................
2
HUMAN
HEALTH
RISK
ASSESSMENT,
JUNE
7,
2002............................................................
3
General.....................................................................................................................................
3
1.0
Executive
Summary..........................................................................................................
3
Dietary
Risk
Estimates....................................................................................................
3
Aggregate
Risks
and
DWLOCs......................................................................................
3
Issues
for
Considerations
................................................................................................
4
4.0
Non
Occupational
Risk
Assessment
and
Characterization...............................................
4
4.1
Summary
of
Registered
Uses...................................................................................
4
4.2
Dietary
Risk
Assessment
.........................................................................................
5
4.3
Estimated
Environmental
Concentrations
in
Water.........................................
5
4.3.1
Environmental
Fate
Characteristics
.......................................................
5
4.4
Residential
Risk
Assessment
...........................................................................
6
4.4.2.2
Residential
Handler
Cancer
Risks
......................................................
6
4.4.3
Residential
Postapplication
Risk
Assessment........................................
6
5.0
Aggregate
Risk
Assessments
and
Risk
Characterization..................................................
7
5.1
Calculation
of
Aggregate
Risks
and
DWLOCs.......................................................
7
5.7
Summary
of
Aggregate
Risks
..................................................................................
7
7.1
Occupational
Handler
Risk
Assessment
..................................................................
8
REVISED
PRODUCT
AND
RESIDUE
CHEMISTRY
CHAPTERS
FOR
THE
REREGISTRATION
ELIGIBILITY
DECISION;
MAY
30,
2002........................................
9
General.....................................................................................................................................
9
Product
Chemistry
Chapter
of
the
RED
Document.................................................................
9
Manufacturing
Use
Products
..........................................................................................
9
Residue
Chemistry
Chapter
of
the
RED
Document
................................................................
9
Regulatory
Background
................................................................................................
10
Summary
of
Science
Findings
......................................................................................
10
GLN
860.1200:
Directions
for
Use...............................................................
10
GLN
860.1380:
Storage
Stability
Data
Plants............................................
10
GLN
860.1500:
Crop
Field
Trials.................................................................
10
GLN
860.1520:
Processed
Food/
Feed
..........................................................
11
GLN
860.1480:
Meat,
Milk,
Poultry,
Eggs
..................................................
11
Tolerance
Reassessment
Summary...............................................................................
12
Table
C.
Tolerance
Reassessment
Summary
for
Carbaryl
...........................
12
Miscellaneous
Typographical
Errors
............................................................................
12
3
Human
Health
Risk
Assessment,
June
7,
2002
General
Several
References
Throughout
the
Document
EPA
statement:
The
company
name
of
the
registrant
is
listed
throughout
the
document
as
Aventis
Corporation,
Aventis
Crop
Sciences,
Aventis
Crop
Science,
and
Aventis
Crop
Science
Corporation.
Aventis'
comment:
Reference
should
be
either
to
Aventis
or
Aventis
CropScience.
1.0
Executive
Summary
Dietary
Risk
Estimates
Page
7;
Paragraph
3;
Lines
4
6
EPA
statement:
"In
livestock
commodities,
carbaryl,
5,6
dihydro
5,6
dihydroxy
carbaryl,
5
methoxy
6
dydroxy
carbaryl
and
all
residues
which
can
be
hydrolyzed
to
carbaryl,
5,6
dihydro
5,6
dihydroxy
carbaryl,
5
methoxy
6
hydroxy
carbaryl
under
acidic
conditions
…."
Aventis'
comment:
Add
"and"
before
"5
methoxy
6
hydroxy
carbaryl
under
acidic
conditions
….".
Aggregate
Risks
and
DWLOCs
Page
11;
Paragraph
4;
Lines
9
14
EPA
statement:
"Additionally,
acute
dietary
risks
were
also
exceeded
for
infants
and
children
(1
to
6
years
old)
at
the
99.9
th
percentile
when
the
Carbamate
Market
Basket
Survey
(CMBS)
was
not
considered
in
the
assessment
(133%
of
aPAD).
However,
the
risk
picture
could
substantively
change
if
residential
risks
are
refined
based
on
updated
use
information
from
the
carbaryl
use
survey
yet
to
be
submitted
to
the
Agency,
and
the
Agency
uses
the
CMBS
data
even
with
the
caveats
associated
with
that
study."
Aventis'
comment:
This
statement
is
inconsistent
with
information
presented
elsewhere
in
the
HED
Chapter.
As
written,
the
statement
implies
that
the
Agency
has
not
yet
approved
the
use
of
the
CMBS
data
in
the
dietary
risk
assessment
for
carbaryl.
However,
EPA
states
in
the
Hazard
Characterization
section
of
the
Executive
Summary,
page
6,
paragraph
2,
line
9,
"Dietary
exposures
were
calculated
using
FDA
and
PDP
monitoring
data,
a
carbamate
market
basket
survey,
and
…"
which
indicates
that
the
EPA
approved
the
use
of
the
CMBS
data.
In
addition,
it
is
stated
on
pages
8
and
31
(Footnotes)
and
page
37,
first
paragraph:
"At
the
present
time,
information
from
the
industry
sponsored
Carbamate
Market
Basket
Survey
has
been
approved
for
use
in
4
dietary
risk
assessments
with
appropriate
characterization
of
uncertainties
associated
with
the
conduct
of
the
study.
Hence,
the
use
of
these
data
in
this
assessment
should
be
considered
with
associated
caveats
…"
Issues
for
Considerations
Page
16,
Paragraph
1,
Lines
19
26
EPA
statement:
It
should
also
be
noted
that
Aventis
Crop
Sciences
is
in
the
process
of
conducting
biological
monitoring
studies
in
residences
where
there
have
been
carbaryl
applications
(sampling
urine
from
children)
and
also
for
field
workers
during
harvesting
and
hand
thinning
operations
in
apples
and
cherries.
Preliminary
results
from
these
studies,
based
on
personal
communication
with
Aventis
scientists
(they
have
not
been
submitted
to
the
Agency
yet),
indicate
body
burden
levels
similar
to
those
calculated
by
the
Agency
for
risk
assessment
purposes.
For
example,
the
turf
risk
assessments
completed
by
the
Agency
are
intended
to
provide
upper
percentile
exposures.
The
data
from
the
monitored
children
appear
to
indicate
similar
results
a
the
upper
percentiles.
Aventis'
comment:
This
statement
does
not
accurately
reflect
the
true
scope
of
the
study
and
would
be
misleading.
The
comment
would
be
more
accurate
as
follows:
"It
should
also
be
noted
that
Aventis
CropScience
has
completed
and
is
in
the
process
of
submitting
to
the
Agency
a
biomonitoring
study
of
individuals
in
residences
following
the
application
by
a
member
of
the
household
to
the
lawn
and
either
the
vegetable
garden
or
ornamental
flowers.
A
biomonitoring
study
of
for
field
workers
during
harvesting
and
hand
thinning
operations
in
apples
and
cherries
will
also
be
submitted
to
the
Agency.
Based
on
personal
communication
with
Aventis
scientists,
preliminary
results
from
the
residential
biomonitoring
study
indicate
that
the
highest
percentiles
of
the
distribution
of
the
younger
children
in
the
homes
were
similar
to
those
predicted
in
the
Agency's
turf
risk
assessment
for
toddlers
that
are
intended
to
represent
the
higher
percentiles
of
the
exposure
distribution."
4.0
Non
Occupational
Risk
Assessment
and
Characterization
4.1
Summary
of
Registered
Uses
Page
28;
Table
3:
Technical
and
Manufacturing
Carbaryl
Products
Aventis'
comment:
Carbaryl
–
Technical
Products
¨
EPA
Registration
No.
45735
24
(99%),
Carbaryl
99%
Technical
Grade
Insecticide,
Burlington
Scientific
Corporation,
should
be
added
to
the
list
of
registered
carbaryl
technical.
¨
EPA
Registration
No.
264
325
(97.5%),
Aventis
CropScience,
should
be
included
in
the
list
of
manufacturing
use
products.
5
Carbaryl
–
Manufacturing
Use
Products
¨
EPA
Registration
No.
5481
190
(46%
FI),
AMVAC
Chemical
corporation
,
is
an
active
registration
and
should
be
added
to
the
list
of
Manufacturing
Use
Products.
(It
is
listed
in
Table
1,
page
2,
of
the
Product
and
Residue
Chemistry
Chapters)
¨
EPA
Registration
No.
4816
270
(97.5%)
is
no
longer
active;
it
was
transferred
to
EPA
Registration
No.
432
982
(97.5%),
Aventis
Environmental
Science
USA
LP,
on
February
22,
2000.
¨
EPA
Registration
No.
4816
407
(1%)
is
no
longer
active;
it
was
transferred
to
Reg.
No.
432
1006
on
February
22,
2000
and
subsequently
transferred
to
Reg.
No.
73049
238,
Valent
Bioscience
Corporation,
on
June
27,
2001
(neither
4816
407
or
432
1006
are
active).
¨
As
stated
above,
EPA
Registration
No.
264
325
(97.5%),
Aventis
CropScience,
should
be
added
to
the
list
of
manufacturing
use
products.
4.2
Dietary
Risk
Assessment
Page
31;
Paragraph
1;
Lines
3
5
EPA
statement:
Carbaryl
is
used
late
in
the
season
at
maximal
seasonal
rates
of
6
12
lb
ai/
acre.
[Note:
A
Special
Local
Needs
registration
in
California
uses
16
lb
ai/
acre
as
a
maximum
rate
on
citrus.]
Aventis'
comment:
The
Section
3
registration
of
carbaryl
products
cover
the
use
on
citrus
at
the
rate
of
5
16
lbs
ai/
acre
in
the
state
of
California
only.
4.3
Estimated
Environmental
Concentrations
in
Water
4.3.1
Environmental
Fate
Characteristics
Section
4.3.1,
Pages
39
40
Aventis'
comment:
The
text
in
section
4.3.1
does
not
include
the
revisions
that
were
made
to
the
EFED
draft
Chapter
and
is
inconsistent.
For
example:
¨
on
Page
39,
first
paragraph
of
Section
4.3.1,
first
sentence
"Carbaryl
and
its
degradate
1
naphthol
are
fairly
mobile
but
are
not
likely
to
persist
or
accumulate
in
the
environment."
¨
on
Page
40,
Paragraph
1,
last
sentence
"Carbaryl
is
mobile
to
very
mobile
in
the
environment
(Kf
=
1.7
to
3.2)."
The
information
in
the
EFED
chapter
has
been
revised
to
¨
"Carbaryl
is
considered
to
be
moderately
mobile
in
soils"
and
the
Kf
range
is
1.7
to
3.5
(EFED
Chapter,
Page
20
–
Table
3;
Page
22
–
Mobility).
¨
"…
literature
information
suggest
that
it
[1
naphthol]
is
less
persistent
and
less
mobile
than
parent
carbaryl.""(
EFED
Chapter,
Page
26,
1
Naphthol
Fate
and
Transport).
6
Section
4.3.1,
Paragraphs
2
and
3
(pages
39
40)
EPA
statement:
In
these
2
paragraphs,
the
chemical
name
for
the
major
carbaryl
degradation
product
is
typed
as
"1
napthol".
Aventis'
comment:
Correct
spelling
is
"1
naphthol".
4.4
Residential
Risk
Assessment
4.4.2.2
Residential
Handler
Cancer
Risks
Page
52;
Paragraph
1;
Lines
11
12
EPA
statement:
"…[
Note:
Scenarios
where
risks
are
still
of
concern
(i.
e.,
<1x10
6
)
are
highlighted
in
the
table.].
Aventis'
comment:
(i.
e.,
"<"
1x10
6
)
should
be
corrected
to
(i.
e.,
">"
1x10
6
).
4.4.3
Residential
Postapplication
Risk
Assessment
Page
59;
Paragraph
1;
Lines
4
6
EPA
statement:
These
levels
were
The
Agency
instead
considers
them
a
qualitative
indicator
that
exposures
in
the
general
population
are
likely
to
occur.
Aventis'
comment:
Words
are
missing
from
the
first
part
of
the
sentence.
Page:
59
Paragraph:
2
Lines:
1
6
EPA
statement:
Aventis
Crop
Science
is
in
the
process
of
conducting
a
biomonitoring
study
with
children
who
live
in
households
where
carbaryl
has
been
used.
Based
on
discussions
with
Aventis,
the
preliminary
results
indicate
that
levels
at
the
highest
percentiles
of
the
distribution
are
similar
to
those
predicted
in
the
Agency's
turf
risk
assessment
for
toddlers
which
are
intended
to
represent
the
higher
percentiles
of
the
exposure
distribution.
A
more
detailed
analysis
will
be
completed
upon
submission
Aventis'
comment:
The
statement
does
not
accurately
reflect
the
true
scope
of
the
study
and
would
be
misleading.
The
comment
would
be
more
accurate
as
follows:
Aventis
CropScience
has
completed
and
is
in
the
process
of
submitting
to
the
Agency
a
biomonitoring
study
of
individuals
in
residences
following
the
application
by
a
member
of
the
household
to
the
lawn
and
either
the
vegetable
garden
or
ornamental
flowers.
Based
on
discussions
with
Aventis,
preliminary
results
indicate
that
the
highest
percentiles
of
the
distribution
of
the
younger
children
in
the
homes
were
similar
to
those
predicted
in
the
Agency's
turf
risk
assessment
for
toddlers
that
are
7
intended
to
represent
the
higher
percentiles
of
the
exposure
distribution.
A
more
detailed
analysis
will
be
completed
upon
submission.
5.0
Aggregate
Risk
Assessments
and
Risk
Characterization
5.1
Calculation
of
Aggregate
Risks
and
DWLOCs
Page
72;
Paragraph
2;
Lines
6
11
EPA
statement:
"Additionally,
acute
dietary
risks
were
also
exceeded
for
infants
and
children
(1
to
6
years
old)
at
the
99.9
th
percentile
when
the
Carbamate
Market
Basket
Survey
(CMBS)
was
not
considered
in
the
assessment.
However,
the
risk
picture
could
substantively
change
if
residential
risks
are
refined
based
on
updated
use
information
from
the
carbaryl
use
survey
yet
to
be
submitted
to
the
Agency
and
the
Agency
chooses
to
regulate
using
the
results
of
the
CMBS."
Aventis'
comment:
This
statement
is
inconsistent
with
information
presented
elsewhere
in
the
HED
Chapter.
As
written,
the
statement
implies
that
the
Agency
has
not
yet
approved
the
use
of
the
CMBS
data
in
the
dietary
risk
assessment
for
carbaryl.
However,
EPA
states
in
the
Hazard
Characterization
section
of
the
Executive
Summary,
page
6,
paragraph
2,
line
9,
"Dietary
exposures
were
calculated
using
FDA
and
PDP
monitoring
data,
a
carbamate
market
basket
survey,
and
…"
which
indicates
that
the
EPA
approved
the
use
of
the
CMBS
data.
In
addition,
it
is
stated
on
pages
8
and
31
(Footnotes)
and
page
37,
first
paragraph:
"At
the
present
time,
information
from
the
industry
sponsored
Carbamate
Market
Basket
Survey
has
been
approved
for
use
in
dietary
risk
assessments
with
appropriate
characterization
of
uncertainties
associated
with
the
conduct
of
the
study.
Hence,
the
use
of
these
data
in
this
assessment
should
be
considered
with
associated
caveats
…"
5.7
Summary
of
Aggregate
Risks
Page
76;
Paragraph
2;
Lines
3
4
continued
on
page
77
EPA
statement:
"Additionally,
acute
dietary
risks
were
also
exceeded
for
infants
and
children
(1
to
6
years
old)
at
the
99.9
th
percentile
when
the
Carbamate
Market
Basket
Survey
(CMBS)
was
not
considered
in
the
assessment.
However,
the
risk
picture
could
substantively
change
if
residential
risks
are
refined
based
on
updated
use
information
from
the
carbaryl
use
survey
yet
to
be
submitted
to
the
Agency
and
the
Agency
chooses
to
regulate
using
the
results
of
the
CMBS."
Aventis'
comment:
This
statement
is
inconsistent
with
information
presented
elsewhere
in
the
HED
Chapter.
As
written,
the
statement
implies
that
the
Agency
has
not
yet
approved
the
use
of
the
CMBS
data
in
the
dietary
risk
assessment
for
carbaryl.
However,
EPA
states
in
the
Hazard
Characterization
section
of
the
Executive
Summary,
page
6,
8
paragraph
2,
line
9,
"Dietary
exposures
were
calculated
using
FDA
and
PDP
monitoring
data,
a
carbamate
market
basket
survey,
and
…"
which
indicates
that
the
EPA
approved
the
use
of
the
CMBS
data.
In
addition,
it
is
stated
on
pages
8
and
31
(Footnotes)
and
page
37,
first
paragraph:
"At
the
present
time,
information
from
the
industry
sponsored
Carbamate
Market
Basket
Survey
has
been
approved
for
use
in
dietary
risk
assessments
with
appropriate
characterization
of
uncertainties
associated
with
the
conduct
of
the
study.
Hence,
the
use
of
these
data
in
this
assessment
should
be
considered
with
associated
caveats
…"
7.1
Occupational
Handler
Risk
Assessment
Page:
83;
Paragraph
5;
Lines
9
10
and
Footnote
EPA
statement:
There
are
no
data
compensation
issues
with
any
of
these
data.
11
.
(Footnote)
11
Non
ORETF
data
included
in
MRIDs
451672
01
and
452507
01
were
from
studies
submitted
by
Aventis
CropScience.
The
propoxur
trigger
sprayer
study
has
a
signed
PHED
data
waiver
but
has
not
been
included
into
PHED.
Aventis'
comment:
Aventis
concurs
that
there
are
no
data
compensation
issues.
However,
the
rationale
presented
for
the
propoxur
trigger
sprayer
study
is
not
accurate.
The
PHED
data
waiver
is
applicable
only
when
the
data
are
in
PHED
and
not
when
cited
outside
of
PHED.
The
propoxur
study
does
not
trigger
data
compensation
because
the
study
is
the
property
of
Bayer
CropScience
which
has
recently
acquired
Aventis
CropScience.
9
Revised
Product
and
Residue
chemistry
Chapters
for
the
Reregistration
Eligibility
Decision;
May
30,
2002
General
Several
References
Throughout
the
Document
EPA
statement:
The
company
name
of
the
registrant
is
listed
throughout
the
document
as
Aventis
Ag
Company.
Aventis'
comment:
Reference
should
be
to
Aventis
CropScience.
Product
Chemistry
Chapter
of
the
RED
Document
Manufacturing
Use
Products
Page
2;
Table
1
–
Registered
Carbaryl
Manufacturing
Use
Products
Aventis'
comment:
¨
EPA
Registration
No.
45735
24
(99%),
Carbaryl
99%
Technical
Grade
Insecticide,
Burlington
Scientific
Corporation,
should
be
added
to
the
list
of
registered
carbaryl
technical.
¨
EPA
Registration
No.
4816
270
(97.5%)
is
no
longer
active;
it
was
transferred
to
EPA
Registration
No.
432
982
(97.5%),
Aventis
Environmental
Science
USA
LP,
on
February
22,
2000.
¨
EPA
Registration
No.
4816
407
(1%)
is
no
longer
active;
it
was
transferred
to
Reg.
No.
432
1006
on
February
22,
2000
and
subsequently
transferred
to
Reg.
No.
73049
238,
Valent
Bioscience
Corporation,
on
June
27,
2001
(neither
4816
407
or
432
1006
are
active).
¨
The
name
of
the
registrant
for
EPA
Registration
No.
769
971
is
Value
Gardens
Supply,
LLC.
Corresponding
corrections
should
be
made
to
the
Product
Chemistry
Section
of
the
Memorandum
for
this
Chapter
and
in
other
sections
of
the
Product
Chemistry
Chapter
of
the
Reregistration
Eligibility
Decision
(RED)
Document.
Residue
Chemistry
Chapter
of
the
RED
Document
Several
References
Throughout
the
Document
EPA
statement:
The
company
name
of
the
registrant
is
listed
throughout
the
document
as
Aventis
Ag
Company,
Aventis
Ag
Co.,
and
Aventis
Crop
Science.
Aventis'
comment:
Reference
should
be
to
Aventis
CropScience.
10
Regulatory
Background
Page
2;
Paragraph
2;
Line
5
EPA
statement:
"…
but
should
not
delay
on
the
reregistration
eligibility
decisions
for
carbaryl."
Aventis'
comment:
Remove
"on"
from
the
sentence
.
"…
but
should
not
delay
on
the
reregistration
…"
Summary
of
Science
Findings
GLN
860.1200:
Directions
for
Use
Page
3;
Table
A1.
Carbaryl
EPs
with
Food/
Feed
Uses
Registered
to
Aventis
Ag
Company
EPA
statement:
EPA
Registration
No.
264
430
is
listed
in
this
table.
Aventis'
comment:
The
registration
of
SEVIN®
brand
Granular
Carbaryl
Insecticide
For
Outdoor
Home
Use,
EPA
Registration
No.
264
430,
was
transferred
to
Aventis
Environmental
Science,
EPA
Registration
No.
432
885
on
February
9,
2000.
GLN
860.1380:
Storage
Stability
Data
Plants
Page
6;
Paragraph
1;
Lines
2
3
EPA
statement:
Additional
data
are
required
depicting
the
storage
stability
of
carbaryl
per
se
in
an
oilseed,
processed
commodities
of
an
oily
crop,
and
a
dried
fruit
stored
for
up
to
10
months.
Aventis'
comment:
Inconsistencies
are
noted
between
the
information
presented
in
the
section
"Summary
of
Science
Findings"
and
Table
B.
Residue
Chemistry
Science
Assessments
for
Reregistration
of
Carbaryl
(page
63)
Paragraph
1
of
the
"GLN
860.1380:
Storage
Stability
Data
–
Plants"
section
indicates
the
need
for
storage
stability
data
for
dried
fruit
(in
addition
to
other
items).
Table
B
data
requirements
(page
63
along
with
footnote
#14
on
page
73)
does
not
request
storage
stability
data
for
dried
fruit;
neither
does
the
4
th
paragraph
on
page
6
(GLN
860.1380).
GLN
860.1500:
Crop
Field
Trials
Page
7;
Paragraph
5
EPA
statement:
11
"In
addition,
conclusions
regarding
the
adequacy
of
the
data
for
alfalfa,
apples,
potatoes
…
are
contingent
upon
receipt
and
acceptance
of
adequate
supporting
storage
stability
data."
Aventis'
comment:
The
statement
is
inconsistent
with
information
elsewhere
in
the
document.
There
is
no
requirement
for
storage
stability
data
on
apples
in
the
"GLN
860.1380:
Storage
Stability
Data
–
Plants"
section
(page
6)
nor
in
Table
B
(page
63
along
with
footnote
#14
on
page
73).
Page
8;
Paragraph
14;
Line
4
EPA
statement:
"However,
additional
residue
data
are
required
if
the
registrant
seeks
tolerances
for
residues
in/
on
succulent,
shelled
pea
and
bean
commodities."
(Also
stated
in
the
Memorandum
on
page
3,
paragraph
3).
Aventis'
comment:
This
statement
is
in
contradiction
with
paragraph
6
of
this
section:
"
…
adequate
magnitude
of
the
residue
data
are
available
on
the
following
crops:
……..
beans
(dried
and
succulent),
…
peas
(dried
and
succulent
.…"
and
Table
B
requirements
for
crop
field
trials
(page
65).
Also,
MRID
43984701
(succulent
bean)
and
MRID
43703102
(Fresh
pea)
were
found
to
be
acceptable.
GLN
860.1520:
Processed
Food/
Feed
Page
9;
Paragraph
1;
Lines
4
6
EPA
statement:
Based
on
the
available
processing
studies,
tolerances
are
required
for
residues
in
citrus
fruit
oil,
raisins
,
wet
apple
pomace,
and
rice
hulls
only.
Aventis'
comment:
EPA
requests
processed
commodity
tolerances
for
(among
other
commodities)
wet
apple
pomace
and
raisins
(see
also
Table
C,
page
85).
Calculations
according
to
the
860.1520
Guidelines
indicates
that
processed
commodity
tolerances
are
not
needed
for
these
commodities.
The
Agency's
statement
appears
to
be
the
result
of
a
mathematical
or
computational
type
error
since
the
860.1520
Guidelines
are
rather
clear
on
determination
of
need
for
processed
commodity
tolerances.
GLN
860.1480:
Meat,
Milk,
Poultry,
Eggs
Page
11;
Paragraph
3;
Line
5
EPA
statement:
"The
calculation
of
the
maximum
dietary
is
tentative
...".
Aventis'
comment:
Add
the
word
"burden"
to
the
statement
"The
calculation
of
the
maximum
dietary
(burden)
is
tentative
...".
12
Page
11;
Paragraph
4;
Lines
1
2
EPA
statement:
"…
tolerances
for
residues
of
carbaryl
per
se
in
livestock
(excluding
swine)
commodities
should
be
reassessed
...".
Aventis'
comment:
The
tolerance
expression
in
GLN
860.1480
should
be
modified
to
agree
with
the
one
in
GLN
860.1300
(page
4):
"...
tolerances
for
ruminant
meat
and
milk
should
be
expressed
as
residues
of
free
and
conjugated
carbaryl,
5,6
dihydro
5,6
dihydroxy
carbaryl,
and
5
methoxy
6
hydroxy
carbaryl."
Tolerance
Reassessment
Summary
Table
C.
Tolerance
Reassessment
Summary
for
Carbaryl
Tolerance
Listed
Under
40
CFR
§180.169(
a);
Page
79
Aventis'
comment:
Under
the
commodity
"Corn,
forage",
Comments
on
"Corn,
sweet,
forage"
:
should
read
"Residue
data
indicate
that
the
tolerance
for
sweet
corn
forage
should
be
increased."
(i.
e.,
replace
"field"
with
"sweet"
in
sentence).
Miscellaneous
Typographical
Errors
Under
"REGULATORY
BACKGROUND",
paragraph
3
of
section,
line
5
(page
2):
remove
"on"
from
the
sentence
"...
should
not
delay
on
the
reregistration
...".
Under
"SUMMARY
OF
SCIENCE
FINDINGS,
GLN
860.1500:
Crop
Field
Trials",
paragraph
4,
line
5,
page
7:
remove
period
(.)
after
"ppm"
in
"...
current
tolerance
of
10
ppm.
and
all
residue
data
...".
Also
in
memorandum,
page
3,
paragraph
1.
Under
"SUMMARY
OF
SCIENCE
FINDINGS,
GLN
860.1520:
Processed
Food/
Feed",
paragraph
2,
line
2
(page
9):
add
"to"
to
the
statement
"...
when
this
concentration
factor
is
applied
(to)
the
HAFT
residue
...".
Footnotes
to
Table
B.
Residue
Chemistry
Science
Assessment
for
Reregistration
of
Carbaryl:
#38:
correct
the
spelling
of
"canceled".
Table
C.
Tolerance
Reassessment
Summary
of
Carbaryl,
under
the
commodity
"Sorghum,
stover"
(under
"Comments":
correct
spelling
of
sorghum).
CARBARYL
PC
Code
No.
056801;
Case
0080
Revised
EFED
Risk
Assessment
of
Carbaryl
in
Support
of
the
Reregistration
Eligibility
Decision
(RED)
–
Phase
1
Error
Correction
–
July
12,
2002
Aventis
CropScience
P.
O.
Box
12014,
2
T.
W.
Alexander
Drive
Research
Triangle
Park,
NC
27709
CARBARYL
Revised
EFED
Risk
Assessment
of
Carbaryl
in
Support
of
the
Reregistration
Eligibility
Decision
(RED)
Phase
1
Error
Correction
TABLE
OF
CONTENTS
TABLE
OF
CONTENTS
................................................................................................................
2
ENVIRONMENTAL
FATE
AND
ECOLOGICAL
RISK
ASSESSMENT
FOR
THE
REREGISTRATION
OF
CARBARYL..................................................................................
3
General.....................................................................................................................................
3
1.0
Summary
and
Environmental
Risk
Conclusions
..............................................................
3
Fate
and
Water
Assessment
............................................................................................
3
3.0
Integrated
Risk
Characterization.......................................................................................
3
Introduction.....................................................................................................................
3
4.0
Environmental
Fate
Assessment
.......................................................................................
4
Exposure
Characterization..............................................................................................
4
5.0
Drinking
Water
Assessment
.............................................................................................
5
Drinking
Water
Modeling...............................................................................................
5
Appendix
D:
Toxicity
Assessment
.........................................................................................
5
Toxicity
to
Terrestrial
Animals.......................................................................................
5
3
Environmental
Fate
and
Ecological
Risk
Assessment
for
the
Reregistration
of
Carbaryl
General
Several
References
Throughout
the
Document
EPA
statement:
The
company
name
of
the
registrant
is
listed
throughout
the
document
as
Aventis
Corporation,
Aventis
Crop
Sciences,
Aventis
Crop
Science,
and
Aventis
Crop
Science
Corporation.
Aventis'
comment:
Reference
should
be
either
to
Aventis
or
Aventis
CropScience.
1.0
Summary
and
Environmental
Risk
Conclusions
Fate
and
Water
Assessment
Page:
4
Paragraph:
1
Line:
16
EPA
statement:
…to
those
reported
n
non
targeted…
Aventis'
comment:
extra
"n"
in
sentence
3.0
Integrated
Risk
Characterization
Introduction
Page:
8
Paragraph:
1
Line:
8
EPA
statement:
alkaline
(pH
half
life
=
5
hours
environments.
Aventis'
comment:
alkaline
(pH
half
life
=
3.2
hours)
environments.
half
life
is
3.2
not
5
hours
as
noted
elsewhere
in
the
document.
Missing
closing
parenthesis.
4
4.0
Environmental
Fate
Assessment
Exposure
Characterization
Page:
17
Paragraph:
3
Line:
last
sentence
EPA
statement:
Detailed
discussion
and
reviews
(DERs)
of
the
studies
that
are
included
in
this
assessment
are
attached
in
Appendix
A.
Aventis'
comment:
It
is
inappropriate
to
include
the
DERs
in
the
RED.
A
sufficiently
detailed
summary
of
study
findings
is
already
included
in
the
EFED
Chapter.
The
summary
of
endpoints
that
is
included
in
the
draft
Carbaryl
EFED
Chapter
is
typical
of
other
Draft
EFED
REDs
that
have
been
issued
recently
and
provides
sufficient
information
to
allow
the
reader
to
determine
the
endpoints
that
were
selected
for
modeling
and
the
justification
for
their
selection.
The
inclusion
of
the
more
detailed
information
present
in
the
DERs
is
unnecessary.
We
have
reviewed
the
dockets
for
many
of
the
RED
documents
that
have
recently
been
issued
(many
other
insecticides
and
several
fungicides)
and
none
of
them
include
DERs
in
any
of
the
preliminary
Environmental
Fate
and
Effects
Assessments.
DERs
should
be
made
available
to
the
public
through
the
regular
procedure
under
the
Freedom
of
Information
Act
after
they
have
been
reviewed
and
cleared
for
confidential
business
information.
The
inclusion
of
the
DERs
in
the
docket
that
is
publicly
available
circumvents
this
process
and
is
a
departure
from
the
procedures
that
have
been
followed
until
now
by
the
Agency.
It
is
unclear
why
the
Agency
chose
to
change
their
policy
for
only
certain
DERs
for
a
single
product
when
adequate
summary
information
is
already
provided
in
the
text
of
the
Carbaryl
EFED
Chapter.
Page:
17
Paragraph:
4
Line:
4
EPA
statement:
lower
levels
(generally
less
than
0.01
µ/
L).
Aventis'
comment:
value
missing
units
(generally
less
than
0.01
µg/
L).
Persistence
Microbially
Mediated
Processes
Page:
22
Paragraph:
2
Line:
1
EPA
statement:
A
number
of
soil
microorganisms
5
Aventis'
comment:
"microorga
nisms"
5.0
Drinking
Water
Assessment
Drinking
Water
Modeling
Page:
33
Table
6
EPA
statement:
Crop
name
–
Sugar
Beats
(MN)
Aventis'
comment:
Correct
spelling
is
Sugar
Beets
Appendix
D:
Toxicity
Assessment
Toxicity
to
Terrestrial
Animals
Mammals,
Acute
and
Chronic
Page:
237
above
Table
4
EPA
statement:
"Although
at
this
time
two
generation
rat
reproduction
study
data
are
not
available,
…"
Aventis'
comment:
A
two
generation
rat
reproduction
study
has
been
submitted
and
found
to
be
acceptable
by
the
Agency
(MRID#
45448101).
| epa | 2024-06-07T20:31:42.536893 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0020/content.txt"
} |
EPA-HQ-OPP-2002-0138-0021 | Supporting & Related Material | "2002-07-31T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
Office
of
Prevention,
Pesticides
and
Toxic
Substances
August
6,
2002
SUBJECT:
Carbaryl:
Agency
Response
To
Aventis
Crop
Science
Error
Correction
Comments
On
Revised
HED
Risk
Assessment
and
Supporting
Documents,
DP
Barcode:
D284591,
PC
Code:
056801
FROM:
Jeffrey
L.
Dawson,
Chemist/
Risk
Assessor
Reregistration
Branch
1
Health
Effects
Division
(7509C)
THRU:
Whang
Phang,
PhD,
Branch
Senior
Scientist
Reregistration
Branch
1
Health
Effects
Division
(7509C)
TO:
Anthony
Britten,
Chemical
Review
Manager
Reregistration
Branch
3
Special
Review
&
Reregistration
Division
(7508C)
Attached
is
the
Agency's
response
to
30
day
error
correction
comments
provided
by
Aventis
Crop
Science
on
the
previous
version
of
the
human
health
effects
risk
assessment
(D281420/
June
7,
2002).
The
registrant
comments
were
included
in
the
document
entitled
Human
Health
Risk
and
Supporting
Documents
Phase
1
Error
Correction
(Date:
July
12,
2002).
The
Agency's
human
health
risk
assessment
was
updated
based
on
a
number
of
the
comments
and
re
issued
on
July
30,
2002
(D284580).
The
intent
of
this
document
is
to
illustrate
how
the
comments
were
considered
in
the
revisions
to
the
risk
assessment.
The
comments
addressed
the
risk
assessment,
the
product
and
residue
chemistry
chapter,
and
the
occupational
and
residential
risk
assessment.
Note
that
only
the
Agency
risk
assessment
and
not
the
supporting
documents
have
been
updated
at
this
point.
The
Agency
response
is
provided
for
each
set
of
comments,
respectively,
in
Sections
1,
2,
and
3
of
this
document
below.
2
Section
1:
Human
Health
Risk
Assessment
The
Aventis
Crop
Science
comments
on
the
human
health
risk
assessment
are
presented
below
as
well
as
the
Agency's
responses
to
each.
Aventis
Crop
Science
Comment
1:
EPA
statement:
The
company
name
of
the
registrant
is
listed
throughout
the
document
as
Aventis
Corporation,
Aventis
Crop
Sciences,
Aventis
Crop
Science,
and
Aventis
Crop
Science
Corporation.
Aventis'
comment:
Reference
should
be
either
to
Aventis
or
Aventis
CropScience.
Agency
Response
To
Aventis
Crop
Science
Comment
1:
The
Agency
has
used
Aventis
Crop
Science
throughout
the
document.
Aventis
Crop
Science
Comment
2:
1.0
Executive
Summary
Dietary
Risk
Estimates
(Page
7;
Paragraph
3;
Lines
4
6)
EPA
statement:
"In
livestock
commodities,
carbaryl,
5,6
dihydro
5,6
dihydroxy
carbaryl,
5
methoxy
6
dydroxy
carbaryl
and
all
residues
which
can
be
hydrolyzed
to
carbaryl,
5,6
dihydro
5,6
dihydroxy
carbaryl,
5
methoxy
6
hydroxy
carbaryl
under
acidic
conditions
…."
Aventis'
comment:
Add
"and"
before
"5
methoxy
6
hydroxy
carbaryl
under
acidic
conditions
….".
Agency
Response
To
Aventis
Crop
Science
Comment
2:
The
"and"
has
been
added.
3
Aventis
Crop
Science
Comment
3:
1.0
Executive
Summary
Aggregate
Risks
and
DWLOCs
(Page
11;
Paragraph
4;
Lines
9
14)
EPA
statement:
"Additionally,
acute
dietary
risks
were
also
exceeded
for
infants
and
children
(1
to
6
years
old)
at
the
99.9
th
percentile
when
the
Carbamate
Market
Basket
Survey
(CMBS)
was
not
considered
in
the
assessment
(133%
of
aPAD).
However,
the
risk
picture
could
substantively
change
if
residential
risks
are
refined
based
on
updated
use
information
from
the
carbaryl
use
survey
yet
to
be
submitted
to
the
Agency,
and
the
Agency
uses
the
CMBS
data
even
with
the
caveats
associated
with
that
study."
Aventis'
comment:
This
statement
is
inconsistent
with
information
presented
elsewhere
in
the
HED
Chapter.
As
written,
the
statement
implies
that
the
Agency
has
not
yet
approved
the
use
of
the
CMBS
data
in
the
dietary
risk
assessment
for
carbaryl.
However,
EPA
states
in
the
Hazard
Characterization
section
of
the
Executive
Summary,
page
6,
paragraph
2,
line
9,
"Dietary
exposures
were
calculated
using
FDA
and
PDP
monitoring
data,
a
carbamate
market
basket
survey,
and
…"
which
indicates
that
the
EPA
approved
the
use
of
the
CMBS
data.
In
addition,
it
is
stated
on
pages
8
and
31
(Footnotes)
and
page
37,
first
paragraph:
"At
the
present
time,
information
from
the
industry
sponsored
Carbamate
Market
Basket
Survey
has
been
approved
for
use
in
dietary
risk
assessments
with
appropriate
characterization
of
uncertainties
associated
with
the
conduct
of
the
study.
Hence,
the
use
of
these
data
in
this
assessment
should
be
considered
with
associated
caveats
…"
Agency
Response
To
Aventis
Crop
Science
Comment
3:
The
Agency
has
considered
this
and
other
comments
related
to
the
use
and
interpretation
of
the
carbamate
market
basket
survey
results
in
a
similar
fashion.
The
intent
of
the
Agency
in
any
risk
assessment
is
to
present
as
broad
a
picture
as
possible
to
risk
managers
so
they
can
make
the
most
informed
decisions
possible
given
the
resources
available.
This
approach
is
very
consistent
with
the
Agency's
available
guidelines
for
exposure
assessment
and
risk
characterization.
In
this
case,
both
the
CMBS
and
the
PDP
data
(as
well
as
the
other
data
used
in
the
Agency's
dietary
risk
assessment)
were
considered
to
be
acceptable
for
use
in
the
risk
assessment.
However,
both
sources
of
data
have
associated
uncertainties
such
as
the
rubbing
issue
in
the
CMBS.
Additionally,
it
should
be
noted
that
if
the
Agency
considers
multiple
sources
of
data
acceptable
for
risk
assessment,
it
does
not
mean
that
the
4
Agency
would
disregard
other
sources
of
information.
This
is
particularly
true
when
each
one
is
considered
to
be
of
high
quality
yet
still
has
uncertainties
associated
with
its
use.
As
such,
the
Agency
has
retained
the
comparative
risk
analyses
based
on
the
use,
or
not,
of
the
CMBS
in
the
recently
revised
risk
assessment
(D284580/
July
30,
2002).
Aventis
Crop
Science
Comment
4:
1.0
Executive
Summary
Issues
for
Consideration
(Page
16,
Paragraph
1,
Lines
19
26)
EPA
statement:
It
should
also
be
noted
that
Aventis
Crop
Sciences
is
in
the
process
of
conducting
biological
monitoring
studies
in
residences
where
there
have
been
carbaryl
applications
(sampling
urine
from
children)
and
also
for
field
workers
during
harvesting
and
hand
thinning
operations
in
apples
and
cherries.
Preliminary
results
from
these
studies,
based
on
personal
communication
with
Aventis
scientists
(they
have
not
been
submitted
to
the
Agency
yet),
indicate
body
burden
levels
similar
to
those
calculated
by
the
Agency
for
risk
assessment
purposes.
For
example,
the
turf
risk
assessments
completed
by
the
Agency
are
intended
to
provide
upper
percentile
exposures.
The
data
from
the
monitored
children
appear
to
indicate
similar
results
a
the
upper
percentiles.
Aventis'
comment:
This
statement
does
not
accurately
reflect
the
true
scope
of
the
study
and
would
be
misleading.
The
comment
would
be
more
accurate
as
follows:
"It
should
also
be
noted
that
Aventis
CropScience
has
completed
and
is
in
the
process
of
submitting
to
the
Agency
a
biomonitoring
study
of
individuals
in
residences
following
the
application
by
a
member
of
the
household
to
the
lawn
and
either
the
vegetable
garden
or
ornamental
flowers.
A
biomonitoring
study
of
field
workers
during
harvesting
and
hand
thinning
operations
in
apples
and
cherries
will
also
be
submitted
to
the
Agency.
Based
on
personal
communication
with
Aventis
scientists,
preliminary
results
from
the
residential
biomonitoring
study
indicate
that
the
highest
percentiles
of
the
distribution
of
the
younger
children
in
the
homes
were
similar
to
those
predicted
in
the
Agency's
turf
risk
assessment
for
toddlers
that
are
intended
to
represent
the
higher
percentiles
of
the
exposure
distribution."
Agency
Response
To
Aventis
Crop
Science
Comment
4:
The
Agency
replaced
the
text
in
the
revised
assessment
with
that
suggested
by
Aventis
Crop
Science.
5
Aventis
Crop
Science
Comment
5:
4.0
Non
Occupational
Risk
Assessment
and
Characterization
4.1
Summary
of
Registered
Uses
(Page
28;
Table
3:
Technical
and
Manufacturing
Carbaryl
Products)
Aventis'
comment:
Carbaryl
–
Technical
Products
°
EPA
Registration
No.
45735
24
(99%),
Carbaryl
99%
Technical
Grade
Insecticide,
Burlington
Scientific
Corporation,
should
be
added
to
the
list
of
registered
carbaryl
technical.
°
EPA
Registration
No.
264
325
(97.5%),
Aventis
CropScience,
should
be
included
in
the
list
of
manufacturing
use
products.
Carbaryl
–
Manufacturing
Use
Products
°
EPA
Registration
No.
5481
190
(46%
FI),
AMVAC
Chemical
corporation
,
is
an
active
registration
and
should
be
added
to
the
list
of
Manufacturing
Use
Products.
(It
is
listed
in
Table
1,
page
2,
of
the
Product
and
Residue
Chemistry
Chapters)
°
EPA
Registration
No.
4816
270
(97.5%)
is
no
longer
active;
it
was
transferred
to
EPA
Registration
No.
432
982
(97.5%),
Aventis
Environmental
Science
USA
LP,
on
February
22,
2000.
°
EPA
Registration
No.
4816
407
(1%)
is
no
longer
active;
it
was
transferred
to
Reg.
No.
432
1006
on
February
22,
2000
and
subsequently
transferred
to
Reg.
No.
73049
238,
Valent
Bioscience
Corporation,
on
June
27,
2001
(neither
4816
407
or
432
1006
are
active).
°
As
stated
above,
EPA
Registration
No.
264
325
(97.5%),
Aventis
CropScience,
should
be
added
to
the
list
of
manufacturing
use
products.
Agency
Response
To
Aventis
Crop
Science
Comment
5:
The
suggested
modifications
have
been
made
to
the
risk
assessment.
Aventis
Crop
Science
Comment
6:
4.0
Non
Occupational
Risk
Assessment
and
Characterization
4.2
Dietary
Risk
Assessment
(Page
31;
Paragraph
1;
Lines
3
5)
EPA
statement:
Carbaryl
is
used
late
in
the
season
at
maximal
seasonal
rates
of
6
12
lb
ai/
acre.
[Note:
A
Special
Local
Needs
registration
in
California
uses
16
lb
ai/
acre
as
a
maximum
rate
on
citrus.]
6
Aventis'
comment:
The
Section
3
registration
of
carbaryl
products
cover
the
use
on
citrus
at
the
rate
of
5
16
lbs
ai/
acre
in
the
state
of
California
only.
Agency
Response
To
Aventis
Crop
Science
Comment
6:
The
suggested
modifications
have
been
made
to
the
risk
assessment.
Aventis
Crop
Science
Comment
7:
4.0
Non
Occupational
Risk
Assessment
and
Characterization
4.3
Estimated
Environmental
Concentrations
in
Water
4.3.1
Environmental
Fate
Characteristics
(Section
4.3.1,
Pages
39
40)
Aventis'
comment:
The
text
in
section
4.3.1
does
not
include
the
revisions
that
were
made
to
the
EFED
draft
Chapter
and
is
inconsistent.
For
example:
°
on
Page
39,
first
paragraph
of
Section
4.3.1,
first
sentence
"Carbaryl
and
its
degradate
1
naphthol
are
fairly
mobile
but
are
not
likely
to
persist
or
accumulate
in
the
environment."
°
on
Page
40,
Paragraph
1,
last
sentence
"Carbaryl
is
mobile
to
very
mobile
in
the
environment
(Kf
=
1.7
to
3.2)."
The
information
in
the
EFED
chapter
has
been
revised
to
°
"Carbaryl
is
considered
to
be
moderately
mobile
in
soils"
and
the
Kf
range
is
1.7
to
3.5
(EFED
Chapter,
Page
20
–
Table
3;
Page
22
–
Mobility).
°
"…
literature
information
suggest
that
it
[1
naphthol]
is
less
persistent
and
less
mobile
than
parent
carbaryl."(
EFED
Chapter,
Page
26,
1
Naphthol
Fate
and
Transport).
Agency
Response
To
Aventis
Crop
Science
Comment
7:
The
suggested
modifications
have
been
made
to
the
risk
assessment.
7
Aventis
Crop
Science
Comment
8:
4.0
Non
Occupational
Risk
Assessment
and
Characterization
4.3
Estimated
Environmental
Concentrations
in
Water
4.3.1
Environmental
Fate
Characteristics
(Section
4.3.1,
Paragraphs
2
and
3
(pages
39
40))
EPA
statement:
In
these
2
paragraphs,
the
chemical
name
for
the
major
carbaryl
degradation
product
is
typed
as
"1
napthol".
Aventis'
comment:
Correct
spelling
is
"1
naphthol".
Agency
Response
To
Aventis
Crop
Science
Comment
8:
The
suggested
modifications
have
been
made
to
the
risk
assessment.
Aventis
Crop
Science
Comment
9:
4.0
Non
Occupational
Risk
Assessment
and
Characterization
4.4
Residential
Risk
Assessment
4.4.2.2
Residential
Handler
Cancer
Risks
(Page
52;
Paragraph
1;
Lines
11
12)
EPA
statement:
"…[
Note:
Scenarios
where
risks
are
still
of
concern
(i.
e.,
<1x10
6
)
are
highlighted
in
the
table.].
Aventis'
comment:
(i.
e.,
"<"
1x10
6
)
should
be
corrected
to
(i.
e.,
">"
1x10
6
).
Agency
Response
To
Aventis
Crop
Science
Comment
9:
The
suggested
modifications
have
been
made
to
the
risk
assessment.
8
Aventis
Crop
Science
Comment
10:
4.0
Non
Occupational
Risk
Assessment
and
Characterization
4.4
Residential
Risk
Assessment
4.4.3
Residential
Postapplication
Risk
Assessment
(Page
59;
Paragraph
1;
Lines
4
6)
EPA
statement:
These
levels
were
The
Agency
instead
considers
them
a
qualitative
indicator
that
exposures
in
the
general
population
are
likely
to
occur.
Aventis'
comment:
Words
are
missing
from
the
first
part
of
the
sentence.
Agency
Response
To
Aventis
Crop
Science
Comment
10:
The
suggested
modifications
have
been
made
to
the
risk
assessment.
Aventis
Crop
Science
Comment
11:
4.0
Non
Occupational
Risk
Assessment
and
Characterization
4.4
Residential
Risk
Assessment
4.4.3
Residential
Postapplication
Risk
Assessment
(Page:
59
Paragraph:
2
Lines:
1
6)
EPA
statement:
Aventis
Crop
Science
is
in
the
process
of
conducting
a
biomonitoring
study
with
children
who
live
in
households
where
carbaryl
has
been
used.
Based
on
discussions
with
Aventis,
the
preliminary
results
indicate
that
levels
at
the
highest
percentiles
of
the
distribution
are
similar
to
those
predicted
in
the
Agency's
turf
risk
assessment
for
toddlers
which
are
intended
to
represent
the
higher
percentiles
of
the
exposure
distribution.
A
more
detailed
analysis
will
be
completed
upon
submission
Aventis'
comment:
The
statement
does
not
accurately
reflect
the
true
scope
of
the
study
and
would
be
misleading.
The
comment
would
be
more
accurate
as
follows:
Aventis
CropScience
has
completed
and
is
in
the
process
of
submitting
to
the
Agency
a
biomonitoring
study
of
individuals
in
residences
following
the
application
by
a
member
of
the
household
to
the
lawn
and
either
the
vegetable
garden
or
ornamental
flowers.
Based
on
discussions
with
Aventis,
preliminary
results
indicate
that
the
highest
percentiles
of
the
distribution
of
the
younger
children
in
the
homes
were
similar
to
those
predicted
in
the
Agency's
turf
risk
assessment
for
toddlers
that
are
intended
to
represent
the
higher
percentiles
of
the
exposure
distribution.
A
more
detailed
analysis
will
be
completed
upon
submission.
9
Agency
Response
To
Aventis
Crop
Science
Comment
11
The
suggested
modifications
have
been
made
to
the
risk
assessment.
Aventis
Crop
Science
Comment
12:
5.0
Aggregate
Risk
Assessments
and
Risk
Characterization
5.1
Calculation
of
Aggregate
Risks
and
DWLOCs
(Page
72;
Paragraph
2;
Lines
6
11)
EPA
statement:
"Additionally,
acute
dietary
risks
were
also
exceeded
for
infants
and
children
(1
to
6
years
old)
at
the
99.9
th
percentile
when
the
Carbamate
Market
Basket
Survey
(CMBS)
was
not
considered
in
the
assessment.
However,
the
risk
picture
could
substantively
change
if
residential
risks
are
refined
based
on
updated
use
information
from
the
carbaryl
use
survey
yet
to
be
submitted
to
the
Agency
and
the
Agency
chooses
to
regulate
using
the
results
of
the
CMBS."
Aventis'
comment:
This
statement
is
inconsistent
with
information
presented
elsewhere
in
the
HED
Chapter.
As
written,
the
statement
implies
that
the
Agency
has
not
yet
approved
the
use
of
the
CMBS
data
in
the
dietary
risk
assessment
for
carbaryl.
However,
EPA
states
in
the
Hazard
Characterization
section
of
the
Executive
Summary,
page
6,
paragraph
2,
line
9,
"Dietary
exposures
were
calculated
using
FDA
and
PDP
monitoring
data,
a
carbamate
market
basket
survey,
and
…"
which
indicates
that
the
EPA
approved
the
use
of
the
CMBS
data.
In
addition,
it
is
stated
on
pages
8
and
31
(Footnotes)
and
page
37,
first
paragraph:
"At
the
present
time,
information
from
the
industry
sponsored
Carbamate
Market
Basket
Survey
has
been
approved
for
use
in
dietary
risk
assessments
with
appropriate
characterization
of
uncertainties
associated
with
the
conduct
of
the
study.
Hence,
the
use
of
these
data
in
this
assessment
should
be
considered
with
associated
caveats
…"
Agency
Response
To
Aventis
Crop
Science
Comment
12:
Please
refer
to
the
Agency
response
to
Aventis
Crop
Science
comment
3
above.
Aventis
Crop
Science
Comment
13:
5.0
Aggregate
Risk
Assessments
and
Risk
Characterization
5.7
Summary
of
Aggregate
Risks
(Page
76;
Paragraph
2;
Lines
3
4
continued
on
page
77)
EPA
statement:
"Additionally,
acute
dietary
risks
were
also
exceeded
for
infants
and
children
(1
to
6
years
old)
at
the
99.9
th
percentile
when
the
Carbamate
Market
Basket
Survey
(CMBS)
was
not
considered
in
the
assessment.
However,
the
risk
picture
10
could
substantively
change
if
residential
risks
are
refined
based
on
updated
use
information
from
the
carbaryl
use
survey
yet
to
be
submitted
to
the
Agency
and
the
Agency
chooses
to
regulate
using
the
results
of
the
CMBS."
Aventis'
comment:
This
statement
is
inconsistent
with
information
presented
elsewhere
in
the
HED
Chapter.
As
written,
the
statement
implies
that
the
Agency
has
not
yet
approved
the
use
of
the
CMBS
data
in
the
dietary
risk
assessment
for
carbaryl.
However,
EPA
states
in
the
Hazard
Characterization
section
of
the
Executive
Summary,
page
6,
paragraph
2,
line
9,
"Dietary
exposures
were
calculated
using
FDA
and
PDP
monitoring
data,
a
carbamate
market
basket
survey,
and
…"
which
indicates
that
the
EPA
approved
the
use
of
the
CMBS
data.
In
addition,
it
is
stated
on
pages
8
and
31
(Footnotes)
and
page
37,
first
paragraph:
"At
the
present
time,
information
from
the
industry
sponsored
Carbamate
Market
Basket
Survey
has
been
approved
for
use
in
dietary
risk
assessments
with
appropriate
characterization
of
uncertainties
associated
with
the
conduct
of
the
study.
Hence,
the
use
of
these
data
in
this
assessment
should
be
considered
with
associated
caveats
…"
Agency
Response
To
Aventis
Crop
Science
Comment
13:
Please
refer
to
the
Agency
response
to
Aventis
Crop
Science
comment
3
above.
Aventis
Crop
Science
Comment
14:
7.1
Occupational
Handler
Risk
Assessment
(Page:
83;
Paragraph
5;
Lines
9
10
and
Footnote)
EPA
statement:
There
are
no
data
compensation
issues
with
any
of
these
data.
11
.
(Footnote)
11
Non
ORETF
data
included
in
MRIDs
451672
01
and
452507
01
were
from
studies
submitted
by
Aventis
CropScience.
The
propoxur
trigger
sprayer
study
has
a
signed
PHED
data
waiver
but
has
not
been
included
into
PHED.
Aventis'
comment:
Aventis
concurs
that
there
are
no
data
compensation
issues.
However,
the
rationale
presented
for
the
propoxur
trigger
sprayer
study
is
not
accurate.
The
PHED
data
waiver
is
applicable
only
when
the
data
are
in
PHED
and
not
when
cited
outside
of
PHED.
The
propoxur
study
does
not
trigger
data
compensation
because
the
study
is
the
property
of
Bayer
CropScience
which
has
recently
acquired
Aventis
CropScience.
Agency
Response
To
Aventis
Crop
Science
Comment
14:
The
suggested
modifications
have
been
made
to
the
risk
assessment.
11
Section
2:
Product
and
Residue
Chemistry
This
section
addresses
the
comments
received
from
Aventis
Crop
Science
pertaining
to
the
product
and
residue
chemistry
supporting
document
(D283328).
This
document
has
not
been
altered
at
this
point
to
reflect
the
changes
suggested
by
the
registrant,
Aventis
Crop
Sciences.
Rather,
specific
changes
which
could
impact
the
results
of
the
risk
assessment
were
considered
and
the
appropriate
modifications
were
made
to
the
risk
assessment.
The
Agency
response
to
comments
provided
by
Aventis
will
serve
as
errata
to
the
product
and
residue
chemistry
chapter
(D283328).
Aventis
Crop
Science
Comment
15:
General
several
References
Throughout
the
Document
EPA
statement:
The
company
name
of
the
registrant
is
listed
throughout
the
document
as
Aventis
Ag
Company.
Aventis'
comment:
Reference
should
be
to
Aventis
CropScience.
[Note:
This
issue
was
repeated
in
the
Aventis
Crop
Science
comments
pertaining
to
the
product
and
residue
chemistry
chapters.
It
is
only
addressed
here.]
Agency
Response
To
Aventis
Crop
Science
Comment
15:
The
suggested
modifications
will
be
made
to
the
product
and
residue
chemistry
chapter
(D283328)
if
and
when
the
document
is
reissued.
Otherwise
the
Agency
acknowledges
this
comment
and
has
altered
the
overall
risk
assessment
document
to
reflect
the
suggested
change.
Aventis
Crop
Science
Comment
16:
Product
Chemistry
Chapter/
Manufacturing
Use
Products
(Page
2;
Table
1
–
Registered
Carbaryl
Manufacturing
Use
Products)
Aventis'
comment:
°
EPA
Registration
No.
45735
24
(99%),
Carbaryl
99%
Technical
Grade
Insecticide,
Burlington
Scientific
Corporation,
should
be
added
to
the
list
of
registered
carbaryl
technical.
°
EPA
Registration
No.
4816
270
(97.5%)
is
no
longer
active;
it
was
transferred
to
EPA
Registration
No.
432
982
(97.5%),
Aventis
Environmental
Science
USA
LP,
on
February
22,
2000.
12
°
EPA
Registration
No.
4816
407
(1%)
is
no
longer
active;
it
was
transferred
to
Reg.
No.
432
1006
on
February
22,
2000
and
subsequently
transferred
to
Reg.
No.
73049
238,
Valent
Bioscience
Corporation,
on
June
27,
2001
(neither
4816
407
or
432
1006
are
active).
°
The
name
of
the
registrant
for
EPA
Registration
No.
769
971
is
Value
Gardens
Supply,
LLC.
Corresponding
corrections
should
be
made
to
the
Product
Chemistry
Section
of
the
Memorandum
for
this
Chapter
and
in
other
sections
of
the
Product
Chemistry
Chapter
of
the
Reregistration
Eligibility
Decision
(RED)
Document.
Agency
Response
To
Aventis
Crop
Science
Comment
16:
The
suggested
modifications
will
be
made
to
the
product
and
residue
chemistry
chapter
(D283328)
if
and
when
the
document
is
reissued.
Otherwise
the
Agency
acknowledges
this
comment
and
has
altered
the
overall
risk
assessment
document
to
reflect
the
suggested
change.
Aventis
Crop
Science
Comment
17:
Regulatory
Background
(Page
2:
Paragraph
2:
Line
5)
EPA
statement:
"...
but
should
not
delay
on
the
reregistration
eligibility
decisions
for
carbaryl."
Aventis'
comment:
Remove
"on"
from
the
sentence,
"...
but
should
not
delay
on
the
reregistration..."
Agency
Response
To
Aventis
Crop
Science
Comment
17:
The
Agency
is
unclear
about
this
comment
but
will
review
the
affected
text
and
make
appropriate
changes.
Aventis
Crop
Science
Comment
18:
Summary
of
Science
Findings
GLN
860.1200:
Directions
for
Use
(Page
3:
Table
A1.
Carbaryl
EPs
with
Food/
Feed
Uses
Registered
to
Aventis
Ag
Company)
EPA
statement:
EPA
Registration
No.
264
430
is
listed
on
this
table.
Aventis'
comment:
The
registration
of
Sevin
Brand
Granular
Carbaryl
Insecticide
For
Outdoor
Home
Use,
EPA
Registration
No.
264
430,
was
transferred
to
Aventis
Environmental
Science,
EPA
Registration
No.
432
885
on
February
9,
2000.
13
Agency
Response
To
Aventis
Crop
Science
Comment
18:
The
appropriate
changes
to
the
product
and
residue
chemistry
chapter
will
be
made
after
verification
by
the
chemical
review
manager.
There
is
no
anticipated
impact
on
the
results
of
the
risk
assessment.
Aventis
Crop
Science
Comment
19:
GLN
860.1380:
Storage
Stability
Data
Plants
(page
6:
Paragraph
1;
Lines
2
3)
EPA
statement:
Additional
data
are
required
depicting
the
storage
stability
of
carbaryl
per
se
in
an
oilseed,
processed
commodities
of
an
oily
crop,
and
a
dried
fruit
stored
up
to
10
months.
Aventis'
comment:
Inconsistencies
are
noted
between
the
information
presented
in
the
section
"Summary
of
Science
Findings"
and
Table
B.
Residue
Chemistry
Science
Assessments
for
Reregistration
of
Carbaryl
(page
63)
Paragraph
1
of
the
"GLN
860.1380:
Storage
Stability
Data
Plants"
section
indicates
the
need
for
storage
stability
data
for
dried
fruit
(in
addition
to
other
items).
Table
B
data
requirements
(page
63
along
with
footnote
#14
on
page
73)
does
not
request
storage
stability
data
for
dried
fruit;
neither
does
the
4
th
paragraph
on
page
6
(GLN
860.1380).
Agency
Response
To
Aventis
Crop
Science
Comment
19:
The
appropriate
modifications
will
be
made
to
the
product
and
residue
chemistry
chapter
(D283328)
if
and
when
the
document
is
reissued.
Otherwise
the
Agency
acknowledges
this
comment
and
has
altered
the
overall
risk
assessment
document
to
reflect
appropriate
changes.
Aventis
Crop
Science
Comment
20:
GLN
860.1500:
Crop
Field
Trials
(Page
7,
paragraph
5)
EPA
statement:
"In
addition,
conclusions
regarding
the
adequacy
of
the
data
for
alfalfa,
apples,
potatoes...
are
contingent
upon
receipt
and
acceptance
of
adequate
supporting
storage
stability
data."
Aventis'
comment:
The
statement
is
inconsistent
with
information
elsewhere
in
the
document.
There
is
no
requirement
for
storage
stability
data
on
apples
in
the
"GLN
860.1380:
Storage
Stability
Data
Plants"
section
(page
6)
nor
in
Table
B
(page
63
along
with
footnote
#14
on
pate
73).
14
Agency
Response
To
Aventis
Crop
Science
Comment
20:
The
appropriate
modifications
will
be
made
to
the
product
and
residue
chemistry
chapter
(D283328)
if
and
when
the
document
is
reissued.
Otherwise
the
Agency
acknowledges
this
comment
and
has
altered
the
overall
risk
assessment
document
to
reflect
appropriate
changes.
Aventis
Crop
Science
Comment
21:
GLN
860.1500:
Crop
Field
Trials
(Page
8,
paragraph
14,
Line
4)
EPA
statement:
"However,
additional
residue
data
are
required
if
the
registrant
seeks
tolerances
for
residues
in/
on
succulent,
shelled
pea
and
bean
commodities."
(Also
stated
in
the
Memorandum
on
page
3,
paragraph
3).
Aventis'
comment:
This
statement
is
in
contradiction
with
paragraph
6
of
this
section:
"...
adequate
magnitude
of
the
residue
data
are
available
on
the
following
crops:
...
beans
(dried
and
succulent),
...
peas
(dried
and
succulent..."
and
Table
B
requirements
for
crop
field
trials
(page
65).
Also,
MRID
43984701
(succulent
bean)
and
MRID
43703102
(fresh
pea)
were
found
to
be
acceptable.
Agency
Response
To
Aventis
Crop
Science
Comment
21:
The
appropriate
modifications
will
be
made
to
the
product
and
residue
chemistry
chapter
(D283328)
if
and
when
the
document
is
reissued
after
verification
by
the
chemical
review
manager.
There
is
no
anticipated
impact
on
the
results
of
the
risk
assessment.
Aventis
Crop
Science
Comment
22:
GLN
860.1520:
Processed
Food/
Feed
(page
9,
paragraph
1,
lines
4
6)
EPA
statement:
Based
on
the
available
processing
studies,
tolerances
are
required
for
residues
in
citrus
fruit
oil,
raisins,
wet
apple
pomace,
and
rice
hulls
only.
Aventis'
comment:
EPA
requests
processed
commodity
tolerances
for
(among
other
commodities)
wet
apple
pomace
and
raisins
(see
also
Table
C,
page
85).
Calculations
according
to
the
860.1520
Guidelines
indicate
that
processed
commodity
tolerances
are
not
needed
for
these
commodities.
The
Agency's
statement
appears
to
be
the
result
of
a
mathematical
or
computational
type
error
since
the
860.1520
Guidelines
are
rather
clear
on
determination
of
need
for
processed
commodity
tolerances.
15
Agency
Response
To
Aventis
Crop
Science
Comment
22:
The
appropriate
modifications
will
be
made
to
the
product
and
residue
chemistry
chapter
(D283328)
if
and
when
the
document
is
reissued.
Otherwise
the
Agency
acknowledges
this
comment
and
has
altered
the
overall
risk
assessment
document
to
reflect
appropriate
changes.
Aventis
Crop
Science
Comment
23:
GLN
860.1480:
Meat,
Milk,
Poultry,
Eggs
(page
11:
paragraph
3,
line
5)
EPA
statement:
"The
calculation
of
the
maximum
dietary
is
tentative..."
Aventis'
comment:
Add
the
word
"burden"
to
the
statement
"The
calculation
of
the
maximum
dietary
(burden)
is
tentative...".
Agency
Response
To
Aventis
Crop
Science
Comment
23:
The
Agency
will
add
the
word
"burden"
to
the
text
of
the
document.
Aventis
Crop
Science
Comment
24:
GLN
860.1480:
Meat,
Milk,
Poultry,
Eggs
(page
11:
paragraph
4,
lines
1
2)
EPA
statement:
"...
tolerances
for
residues
of
carbaryl
per
se
in
livestock
(excluding
swine)
commodities
should
be
reassessed..."
Aventis'
comment:
The
tolerance
expression
in
GLN
860.1480
should
be
modified
to
agree
with
the
one
in
GLN
860.1300
(page
4):
"...
tolerances
for
ruminant
meat
and
milk
should
be
expressed
as
residues
of
free
and
conjugated
carbaryl,
5,6
dihydro
5,6
dihydroxy
carbaryl,
and
5
methoxy
6
hydroxy
carbaryl."
Agency
Response
To
Aventis
Crop
Science
Comment
24:
The
appropriate
modifications
will
be
made
to
the
product
and
residue
chemistry
chapter
(D283328)
if
and
when
the
document
is
reissued.
Otherwise
the
Agency
acknowledges
this
comment
and
has
altered
the
overall
risk
assessment
document
to
reflect
appropriate
changes.
16
Aventis
Crop
Science
Comment
25:
Tolerance
Reassessment
Summary,
Table
C.
Tolerance
Reassessment
Summary
For
Carbaryl,
Tolerance
Listed
Under
40
CFR
§180.169
(a),
page
79
Aventis'
comment:
Under
the
commodity
"Corn,
forage",
Comments
on
"Corn,
sweet,
forage":
should
read
"Residue
data
indicate
that
the
tolerance
for
sweet
corn
forage
should
be
increased."
(i.
e.,
replace
"field"
with
"sweet"
in
the
sentence).
Agency
Response
To
Aventis
Crop
Science
Comment
25:
The
appropriate
modifications
will
be
made
to
the
product
and
residue
chemistry
chapter
(D283328)
if
and
when
the
document
is
reissued.
Otherwise
the
Agency
acknowledges
this
comment
and
has
altered
the
overall
risk
assessment
document
to
reflect
appropriate
changes.
17
Section
3:
Occupational
&
Residential
Exposure
This
section
addresses
the
comments
received
from
Aventis
Crop
Science
pertaining
to
the
occupational
and
residential
exposure
supporting
document
(D281418).
This
document
has
not
been
altered
at
this
point
to
reflect
the
changes
suggested
by
the
registrant,
Aventis
Crop
Sciences.
Rather,
specific
changes
which
could
impact
the
results
of
the
risk
assessment
were
considered
and
the
appropriate
modifications
were
made
to
the
risk
assessment.
The
Agency
response
to
comments
provided
by
Aventis
will
serve
as
errata
to
the
occupational
and
residential
exposure/
risk
assessment
chapter
(D281418).
Aventis
Crop
Science
Comment
26:
General,
Several
References
Throughout
the
Document
EPA
statement:
The
company
name
of
the
registrant
is
listed
throughout
the
document
as
Aventis
Corporation
and
Aventis
Crop
Science.
Aventis'
comment:
Reference
should
either
to
Aventis
or
Aventis
CropScience.
Agency
Response
To
Aventis
Crop
Science
Comment
26:
The
suggested
modifications
will
be
made
to
the
occupational
and
residential
exposure
chapter
(D281418)
if
and
when
the
document
is
reissued.
Otherwise
the
Agency
acknowledges
this
comment
and
has
altered
the
overall
risk
assessment
document
to
reflect
the
suggested
change.
Aventis
Crop
Science
Comment
27:
Executive
Summary
(Page
10,
paragraph:
3,
Lines
16
20)
EPA
comment:
[Note:
The
Aventis
Corporation
is
in
the
process
of
conducting
a
biomonitoring
study
with
children
who
live
in
households
where
carbaryl
has
been
used.
Preliminary
results
indicate
that
levels
at
the
highest
percentiles
of
the
distribution
were
similar
to
those
predicted
in
the
Agency's
turf
risk
assessment
for
toddlers
which
are
intended
to
represent
the
higher
percentiles
of
the
exposure
distribution.
A
more
detailed
analysis
will
be
completed
upon
submission.]
Aventis's
response:
The
statement
does
not
accurately
reflect
the
true
scope
of
the
study
and
would
be
misleading.
The
comment
would
be
more
accurate
as
follows:
Aventis
Crop
Science
has
completed
and
is
in
the
process
of
submitting
to
the
Agency
a
biomonitoring
study
of
individuals
in
residences
following
the
application
by
a
member
of
the
household
to
the
lawn
and
either
the
vegetable
garden
or
ornamental
18
flowers.
Preliminary
results
indicate
that
the
highest
percentiles
of
the
distribution
of
the
younger
children
in
the
homes
were
similar
to
those
predicted
in
the
Agency's
turf
risk
assessment
for
toddlers
that
are
intended
to
represent
the
higher
percentiles
of
the
exposure
distribution.
A
more
detailed
analysis
will
be
completed
upon
submission.
Agency
Response
To
Aventis
Crop
Science
Comment
27:
The
suggested
modifications
will
be
made
to
the
occupational
and
residential
exposure
chapter
(D281418)
if
and
when
the
document
is
reissued.
Otherwise
the
Agency
acknowledges
this
comment
and
has
altered
the
overall
risk
assessment
document
to
reflect
the
suggested
change.
Aventis
Crop
Science
Comment
28:
1.0
Occupational
and
Residential
Exposure/
Risk
Assessment
1.5
Summary
of
Use
Patterns
and
Formulations
1.5.1
End
Use
Products
(page
15,
table
2)
Aventis'
comment:
Carbaryl
–
Technical
Products
°
EPA
Registration
No.
45735
24
(99%),
Carbaryl
99%
Technical
Grade
Insecticide,
Burlington
Scientific
Corporation,
should
be
added
to
the
list
of
registered
carbaryl
technical.
°
EPA
Registration
No.
264
325
(97.5%),
Aventis
CropScience,
should
be
included
in
the
list
of
manufacturing
use
products.
Carbaryl
–
Manufacturing
Use
Products
°
EPA
Registration
No.
5481
190
(46%
FI),
AMVAC
Chemical
corporation
,
is
an
active
registration
and
should
be
added
to
the
list
of
Manufacturing
Use
Products.
(It
is
listed
in
Table
1,
page
2,
of
the
Product
and
Residue
Chemistry
Chapters)
°
EPA
Registration
No.
4816
270
(97.5%)
is
no
longer
active;
it
was
transferred
to
EPA
Registration
No.
432
982
(97.5%),
Aventis
Environmental
Science
USA
LP,
on
February
22,
2000.
°
EPA
Registration
No.
4816
407
(1%)
is
no
longer
active;
it
was
transferred
to
Reg.
No.
432
1006
on
February
22,
2000
and
subsequently
transferred
to
Reg.
No.
73049
238,
Valent
Bioscience
Corporation,
on
June
27,
2001
(neither
4816
407
or
432
1006
are
active).
°
As
stated
above,
EPA
Registration
No.
264
325
(97.5%),
Aventis
CropScience,
should
be
added
to
the
list
of
manufacturing
use
products.
19
Agency
Response
To
Aventis
Crop
Science
Comment
28:
The
suggested
modifications
will
be
made
to
the
occupational
and
residential
exposure
chapter
(D281418)
if
and
when
the
document
is
reissued
pending
verification
by
the
chemical
review
manager.
Otherwise
the
Agency
acknowledges
this
comment
and
has
altered
the
overall
risk
assessment
document
to
reflect
the
suggested
change.
[Note:
This
comment
was
also
addressed
above
in
the
risk
assessment
section.]
Aventis
Crop
Science
Comment
29:
1.5.3
Registered
Use
Categories
and
Sites
(page
20,
animal
uses)
EPA
statement:
Poultry
(Chickens,
ducks,
geese,
game
birds,
turkeys)
Livestock
(cattle,
sheep,
horses,
etc.)
Aventis'
comment:
Both
uses
should
be
removed
from
the
list
of
registered
uses.
Aventis
voluntarily
requested
the
deletion
of
the
use
on
poultry.
A
Federal
Register
Notice
dated
October
24,
2001
announced
receipt
by
the
Agency
of
an
application
from
Aventis
Crop
Science
to
delete
this
use.
The
use
on
livestock
(cattle,
sheep,
horses,
etc.)
is
no
longer
registered.
Aventis
will
not
support
the
reregistration
of
this
use.
Agency
Response
To
Aventis
Crop
Science
Comment
29:
The
suggested
modifications
will
be
made
to
the
occupational
and
residential
exposure
chapter
(D281418)
if
and
when
the
document
is
reissued
once
the
suggested
changes
are
verified
by
the
chemical
review
manager.
It
should
be
noted
that
an
August
1,
2002
review
of
the
Agency's
REFs
system
still
had
active
registrations
listed
for
both
poultry
and
unspecified
livestock
and
horses.
There
were
some
registrations
for
cattle
that
were
listed
as
inactive.
Aventis
Crop
Science
Comment
30:
1.5.3
Registered
Use
Categories
and
Sites
(page
21,
aquatic
food
crop)
EPA
statement:
Aquatic
sites
commercial
fishery
water
systems
Aventis'
comment:
This
use
is
not
listed
on
Aventis
Carbaryl
product
labels.
20
Agency
Response
To
Aventis
Crop
Science
Comment
30:
The
use
likely
attributed
to
this
site
is
from
EPA
Reg.
No.
264
316,
SLN
WA
900013
which
is
for
Sevin
Brand
80S
Carbaryl
Insecticide
For
Control
Of
Ghost
and
Mud
Shrimp
in
Oyster
Beds
in
Washington
state.
Aventis
Crop
Science
Comment
31:
1.5.3
Registered
Use
Categories
and
Sites
(page
21,
aquatic
non
food
industrial)
EPA
statement:
Aquatic
sites
drainage
systems
Aventis'
comment:
This
use
is
not
listed
on
Aventis
carbaryl
products
labels.
Agency
Response
To
Aventis
Crop
Science
Comment
31:
The
suggested
modifications
will
be
made
to
the
occupational
and
residential
exposure
chapter
(D281418)
if
and
when
the
document
is
reissued
once
the
suggested
changes
are
verified
by
the
chemical
review
manager
and
another
review
of
available
labels
is
completed.
It
should
be
noted
that
an
August
1,
2002
review
of
the
Agency's
REFs
system
still
had
an
active
registration
for
this
site.
Aventis
Crop
Science
Comment
32:
2.0
Occupational
Exposures
and
Risks
2.1
Occupational
Handler
Exposures
and
Risks
2.1.2
Data
and
Assumptions
For
Handler
Exposure
Scenarios
(page
36,
paragraph
1,
lines
1
4)
EPA
statement:
There
are
no
data
compensation
issues
associated
with
the
use
of
nonORETF
data...
and
the
propoxur
trigger
sprayer
study
has
a
signed
PHED
data
waiver
but
just
has
not
been
included
into
PHED
at
this
time.
Aventis'
response:
Aventis
concurs
that
there
are
no
data
compensation
issues.
However,
the
rationale
for
the
propoxur
trigger
sprayer
study
is
not
correct.
The
PHED
data
waiver
is
applicable
only
when
the
data
are
in
PHED
and
not
when
cited
outside
of
PHED.
The
propoxur
study
does
not
trigger
data
compensation
because
the
study
is
the
property
of
Bayer
Crop
Science
which
has
acquired
Aventis
Crop
Science.
21
Agency
Response
To
Aventis
Crop
Science
Comment
32:
The
suggested
modifications
will
be
made
to
the
occupational
and
residential
exposure
chapter
(D281418)
if
and
when
the
document
is
reissued.
Otherwise
the
Agency
acknowledges
this
comment
and
has
altered
the
overall
risk
assessment
document
to
reflect
the
suggested
change.
[Note:
This
comment
was
also
addressed
above
in
the
risk
assessment
section.]
Aventis
Crop
Science
Comment
33:
3.0
Residential
and
Other
Non
Occupational
Exposures
and
Risks
3.1
Residential
Handler
Exposures
and
Risks
3.1.2
Data
and
Assumptions
For
Handler
Exposure
Scenarios
(page
99,
paragraph:
2,
line
9)
EPA
statement:
"Longitudinal
data,
however,
were
not
available
to
establish
that
such
populations
definitively
exist."
Aventis'
comment:
The
following
should
be
added
after
this
sentence
to
accurately
reflect
the
submission
of
Residential
Exposure
Joint
Venture
data
for
carbaryl
that
covers
use
patterns
by
the
same
individuals
between
May
and
August.
"Note:
Aventis
has
recently
submitted
an
analysis
of
longitudinal
residential
use
patterns
of
carbaryl
that
monitored
the
use
of
carbaryl
within
several
thousand
households
between
the
months
of
May
through
August."
Agency
Response
To
Aventis
Crop
Science
Comment
33:
At
the
time
the
occupational
and
residential
exposure/
risk
assessment
was
completed,
the
Residential
Exposure
Joint
Venture
data
for
carbaryl
had
not
yet
been
submitted
by
Aventis
Crop
Science.
The
Agency
will
review
this
information,
both
in
the
context
of
a
deterministic
and
a
probabilistic
risk
assessment
strategy.
Results
from
this
study
will
be
incorporated
into
any
revisions
to
the
human
health
risk
assessment
and
the
occupational
and
residential
exposure/
risk
assessment
documents
as
appropriate.
22
Aventis
Crop
Science
Comment
34:
3.0
Residential
and
Other
Non
Occupational
Exposures
and
Risks
3.1
Residential
Handler
Exposures
and
Risks
3.1.2
Data
and
Assumptions
For
Handler
Exposure
Scenarios
(pages
104
105,
Discussion
of
OMA004)
EPA
statement:
The
discussion
presents
exposure
data
for
Dial
type
(DTS)
Homeowner
Hose
End
sprayers
and
Ready
to
Use
Sprayers.
However,
Table
23
and
subsequent
risk
and
exposure
tables
only
present
exposure
estimates
based
on
the
DTS
sprayer.
Aventis'
response:
The
RTU
sprayer
is
an
important
component
of
the
carbaryl
market
and
was
developed
as
an
exposure
mitigation
product
that
eliminates
the
homeowner's
need
to
pour
concentrated
formulations
of
carbaryl.
The
OMA004
study
demonstrated
significant
reductions
in
the
exposure
to
homeowners
and
the
presentation
of
the
resultant
RTU
hose
end
sprayer
data,
exposure,
and
risk
is
essential
to
the
residential
handler
section.
Agency
Response
To
Aventis
Crop
Science
Comment
34:
The
Agency
did
not
include
a
quantitative
analysis
based
on
the
ready
to
use
(no
mixing/
loading)
product
because
it
is
unclear
if
the
packaging
used
in
the
study
is
similar
to
the
containers
used
for
carbaryl
and
it
is
also
not
clear
what
percentage
of
the
market
for
carbaryl
is
accounted
for
by
the
no
mix
containers.
The
Agency
calculated
risk
estimates
based
solely
on
the
hose
end
sprayer
data
that
required
users
to
add
concentrated
formulation
to
the
device.
Both
sets
of
information
will
be
considered
in
any
risk
management
decision.
The
Agency
used
the
following
unit
exposures
in
its
assessment
(i.
e.,
the
open
mixing
data
from
ORETF
Study
OMA004):
°
Dermal
geo.
mean
for
a
person
wearing
shorts
and
a
short
sleeved
shirt:
11
mg/
lb
ai
°
Inhalation
geo.
mean
for
a
person
not
wearing
a
respirator:
16
µg/
lb
ai
[Dermal
exposure
drives
the
overall
risk
estimate
so
any
change
in
dermal
exposure
would
clearly
and
proportionally
alter
the
overall
risk
estimate.
The
total
MOE
(includes
both
dermal
and
inhalation
exposures)
for
broadcast
applications
to
lawns
is
25
while
the
MOE
for
spot
treatments
is
495
(Agency
target
is
100).]
The
unit
exposure
values
from
ORETF
Study
OMA004
where
no
mixing
dial
type
sprayers
were
used
are
as
follows:
°
Dermal
geo.
mean
for
a
person
wearing
shorts
and
a
short
sleeved
shirt:
2.6
mg/
lb
ai
°
Inhalation
geo.
mean
for
a
person
not
wearing
a
respirator:
11
µg/
lb
ai
23
If
the
MOE
for
broadcast
applications
is
adjusted
for
changes
in
the
dermal
exposure
estimate,
then
the
MOE
would
be
~106
(25*
11/
2.6)
which
exceeds
Agency
targets.
This
information
will
be
considered
in
the
risk
management
decisions
as
well
as
the
feasability
of
using
the
no
mix
containers
in
100
percent
of
the
carbaryl
market.
Aventis
Crop
Science
Comment
35:
3.2
Residential
Postapplication
Exposures
and
Risks
3.2.2
Data
and
Assumptions
For
Residential
Postapplication
Exposure
Scenarios
(Page:
122
Paragraph:
5
Lines:
1
6)
EPA
statement:
Aventis
Crop
Science
is
in
the
process
of
conducting
a
biomonitoring
study
with
children
who
live
in
households
where
carbaryl
has
been
used.
Preliminary
results
indicate
that
levels
at
the
highest
percentiles
of
the
distribution
were
similar
to
those
predicted
in
the
Agency's
turf
risk
assessment
for
toddlers
which
are
intended
to
represent
the
higher
percentiles
of
the
exposure
distribution.
A
more
detailed
analysis
will
be
completed
upon
submission
Aventis'
comment:
The
statement
does
not
accurately
reflect
the
true
scope
of
the
study
and
would
be
misleading.
The
comment
would
be
more
accurate
as
follows:
Aventis
CropScience
has
completed
and
is
in
the
process
of
submitting
to
the
Agency
a
biomonitoring
study
of
individuals
in
residences
following
the
application
by
a
member
of
the
household
to
the
lawn
and
either
the
vegetable
garden
or
ornamental
flowers.
Preliminary
results
indicate
that
the
highest
percentiles
of
the
distribution
of
the
younger
children
in
the
homes
were
similar
to
those
predicted
in
the
Agency's
turf
risk
assessment
for
toddlers
that
are
intended
to
represent
the
higher
percentiles
of
the
exposure
distribution.
A
more
detailed
analysis
will
be
completed
upon
submission.
Agency
Response
To
Aventis
Crop
Science
Comment
35:
The
suggested
modifications
have
been
made
to
the
risk
assessment.
Aventis
Crop
Science
Comment
36:
3.2.4
Residential
Postapplication
Exposure
and
Noncancer
Risk
Estimates
(page
132
and
135,
Tables
26
and
28)
EPA
comment:
The
residential
turf
(lawncare)
scenario
does
not
differentiate
between
liquid
spray
and
granular
formulation
applications.
24
Aventis'
response:
There
is
significant
differences
in
the
postapplication
exposure
potential
following
a
liquid
spray
application
compared
to
a
granular
application.
ORETF
data
submitted
to
the
Agency
indicate
that
transferable
residues
following
a
granular
application
are
about
10
times
less
than
a
liquid
spray
application
.
In
addition,
ORETF
has
recently
conducted
a
large
postapplication
exposure
study
in
Moses
Lake,
Washington
that
will
provide
both
adult
Jazzercise
and
Children's
Activity
Pattern
(CHAPs)
transfer
coefficients.
Although
the
Moses
Lake
data
have
not
yet
been
submitted,
the
conduct
of
the
study
should
be
referenced
and
the
tables
should
differentiate
between
the
very
different
liquid
spray
and
granular
lawn
postapplication
exposure
scenarios.
Agency
Response
To
Aventis
Crop
Science
Comment
36:
The
Agency
acknowledges
this
comment
and
will
incorporate
data
from
this
study
as
appropriate
in
the
risk
assessment
and
risk
management
process.
It
should
be
noted
that
even
there
appears
to
be
differences
between
TTR
(turf
transferable
residues)
levels
after
liquid
or
granular
formulation
applications,
Aventis
Crop
Science
only
completed
a
TTR
study
using
a
liquid
formulation
of
carbaryl.
| epa | 2024-06-07T20:31:42.558340 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0138-0021/content.txt"
} |
EPA-HQ-OPP-2002-0142-0001 | Rule | "2002-07-26T04:00:00" | 1-Methylcycloropene; Exemption from the Requirement of a Tolerance | 48796
Federal
Register
/
Vol.
67,
No.
144
/
Friday,
July
26,
2002
/
Rules
and
Regulations
*
*
*
*
*
[
FR
Doc.
02
18867
Filed
7
25
02;
8:
45
am]
BILLING
CODE
6560
50
S
ENVIRONMENTAL
PROTECTION
AGENCY
40
CFR
Part
180
[
OPP
2002
0142;
FRL
7187
4]
1
Methylcyclopropene;
Exemption
from
the
Requirement
of
a
Tolerance
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Final
rule.
SUMMARY:
This
regulation
establishes
an
exemption
from
the
requirement
of
a
tolerance
for
residues
of
1
Methylcyclopropene
(
1
MCP)
in
or
on
fruits
and
vegetables
when
used
as
a
post
harvest
plant
growth
regulator,
i.
e.,
for
the
purpose
of
inhibiting
the
effects
of
ethylene.
AgroFresh,
Inc.
(
formerly
BioTechologies
for
Horticulture)
submitted
a
petition
to
EPA
under
the
Federal
Food,
Drug,
and
Cosmetic
Act,
as
amended
by
the
Food
Quality
Protection
Act
of
1996,
requesting
an
exemption
from
the
requirement
of
a
tolerance.
This
regulation
eliminates
the
need
to
establish
a
maximum
permissible
level
for
residues
of
1
MCP.
DATES:
This
regulation
is
effective
July
26,
2002.
Objections
and
requests
for
hearings,
identified
by
docket
ID
number
OPP
2002
0142,
must
be
received
on
or
before
September
24,
2002.
ADDRESSES:
Written
objections
and
hearing
requests
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
Unit
IX.
of
the
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
EPA,
your
objections
and
hearing
requests
must
identify
docket
ID
number
OPP
2002
0142
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
By
mail:
Driss
Benmhend,
c/
o
Product
Manager
(
PM)
90,
Biopesticides
and
Pollution
Prevention
Division
(
7511C),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(
703)
308
9525;
e
mail
address:
Benmhend.
driss@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
You
may
be
affected
by
this
action
if
you
are
an
agricultural
producer,
food
manufacturer,
or
pesticide
manufacturer.
Potentially
affected
categories
and
entities
may
include,
but
are
not
limited
to:
Categories
NAICS
codes
Examples
of
potentially
affected
entities
Industry
111
Crop
production
112
Animal
production
311
Food
manufacturing
32532
Pesticide
manufacturing
This
listing
is
not
intended
to
be
exhaustive,
but
rather
provides
a
guide
for
readers
regarding
entities
likely
to
be
affected
by
this
action.
Other
types
of
entities
not
listed
in
the
table
could
also
be
affected.
The
North
American
Industrial
Classification
System
(
NAICS)
codes
have
been
provided
to
assist
you
and
others
in
determining
whether
or
not
this
action
might
apply
to
certain
entities.
If
you
have
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
this
Document
and
Other
Related
Documents?
1.
Electronically.
You
may
obtain
electronic
copies
of
this
document,
and
certain
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
at
http://
www.
epa.
gov/.
To
access
this
document,
on
the
Home
Page
select
``
Laws
and
Regulations,''
``
Regulations
and
Proposed
Rules,''
and
then
look
up
the
entry
for
this
document
under
the
``
Federal
Register
Environmental
Documents.''
You
can
also
go
directly
to
the
Federal
Register
listings
at
http://
www.
epa.
gov/
fedrgstr/.
A
frequently
updated
electronic
version
of
40
CFR
part
180
is
available
at
http://
www.
access.
gpo.
gov/
nara/
cfr/
cfrhtml_
00/
Title_
40/
40cfr180_
00.
html.
2.
In
person.
The
Agency
has
established
an
official
record
for
this
action
under
docket
ID
number
OPP
2002
0142.
The
official
record
consists
of
the
documents
specifically
referenced
in
this
action,
and
other
information
related
to
this
action,
including
any
information
claimed
as
Confidential
Business
Information
(
CBI).
This
official
record
includes
the
documents
that
are
physically
located
in
the
docket,
as
well
as
the
documents
that
are
referenced
in
those
documents.
The
public
version
of
the
official
record
does
not
include
any
information
claimed
as
CBI.
The
public
version
of
the
official
record,
which
includes
printed,
paper
versions
of
any
electronic
comments
submitted
during
an
applicable
comment
period
is
available
for
inspection
in
the
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(
703)
305
5805.
II.
Background
and
Statutory
Findings
In
the
Federal
Register
of
June
21,
2000
(
65
FR
38550)
(
FRL
6589
5),
EPA
issued
a
notice
pursuant
to
section
408(
d)(
3)
of
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
21
U.
S.
C.
346a(
d)(
3),
as
amended
by
the
Food
Quality
Protection
Act
(
FQPA)
(
Public
Law
104
170),
announcing
the
filing
of
a
pesticide
tolerance
petition
(
PP
OF6144)
by
AgroFrech,
Inc.
(
formerly
BioTechnologies
for
Horticulture,
Inc.),
100
Independence
Mall
West,
Philadelphia,
PA
19106
2399.
As
required
by
section
408(
d)(
2)(
A)(
i)(
I),
this
notice
included
a
summary
of
the
petition
prepared
by
the
petitioner
AgroFresh,
Inc.
There
were
no
comments
received
in
response
to
the
notice
of
filing.
Section
408(
c)(
2)(
A)(
i)
of
the
FFDCA
allows
EPA
to
establish
an
exemption
from
the
requirement
for
a
tolerance
(
the
legal
limit
for
a
pesticide
chemical
residue
in
or
on
a
food)
only
if
EPA
determines
that
the
tolerance
is
``
safe.''
Section
408(
c)(
2)(
A)(
ii)
defines
``
safe''
to
mean
that
``
there
is
a
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
the
pesticide
chemical
residue,
including
all
anticipated
dietary
exposures
and
all
other
exposures
for
which
there
is
reliable
information.''
This
includes
exposure
through
drinking
water
and
in
residential
settings,
but
does
not
include
occupational
exposure.
Section
408(
b)(
2)(
C)
requires
EPA
to
give
special
consideration
to
exposure
of
infants
and
children
to
the
pesticide
chemical
residue
in
establishing
a
tolerance
and
to
``
ensure
that
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
and
children
from
aggregate
exposure
to
the
pesticide
chemical
residue.
.
.
.''
Additionally,
section
408(
b)(
2)(
D)
requires
that
the
Agency
consider
``
available
information''
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
``
other
substances
that
have
a
common
mechanism
of
toxicity.''
EPA
performs
a
number
of
analyses
to
determine
the
risks
from
aggregate
exposure
to
pesticide
residues.
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/
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67,
No.
144
/
Friday,
July
26,
2002
/
Rules
and
Regulations
EPA
determines
the
toxicity
of
pesticides.
Second,
EPA
examines
exposure
to
the
pesticide
through
food,
drinking
water,
and
through
other
exposures
that
occur
as
a
result
of
pesticide
use
in
residential
settings.
III.
Toxicological
Profile
Consistent
with
section
408(
b)(
2)(
D)
of
FFDCA,
EPA
has
reviewed
the
available
scientific
data
and
other
relevant
information
in
support
of
this
action
and
considered
its
validity,
completeness,
and
reliability
and
the
relationship
of
this
information
to
human
risk.
EPA
has
also
considered
available
information
concerning
the
variability
of
the
sensitivities
of
major
identifiable
subgroups
of
consumers,
including
infants
and
children.
The
end
use
product,
a
white
powder,
when
mixed
with
water
or
a
buffer
solution
releases
the
gas
1
MCP.
The
active
ingredient
acts
an
inhibitor
to
ethylene,
by
blocking
the
attachment
of
ethylene
to
tissue,
and
thus,
prolongs
the
life
of
the
food
commodity
treated.
Toxicity
studies
submitted
in
support
of
the
tolerance
exemption
petition,
and
the
Agency
reviews
are
compiled
in
the
official
record
established
for
this
action
under
the
docket
ID
number
OPP
2002
0142.
1.
Acute
toxicity
(
MRIDs
444647
04
to
08).
1
MCP
exhibits
low
acute
toxicity.
It
is
a
category
IV
biopesticide.
The
rat
oral
LD50
is
greater
than
5,000
milligrams/
kilograms
(
mg/
kg),
the
rabbit
dermal
LD50
is
greater
than
2,000
mg/
kg
and
the
rat
inhalation
LC50
is
greater
than
2.5
milligram/
liter
(
mg/
L)
(
or
greater
than
1,126
parts
per
million
(
ppm)
v/
v
active
ingredient
in
air).
No
deaths
or
clinical
signs
of
systemic
toxicity
were
observed
following
these
acute
exposures.
1
MCP
produces
minimal
irritation
of
skin
and
eyes
in
rabbits
and
1
MCP
is
not
a
skin
sensitizer.
No
hypersensitivity
incidents
were
observed
following
exposure
to
1
MCP.
2.
Genotoxicity
(
MRID
444647
09).
1
MCP
was
not
mutagenic
when
tested
as
a
gas
in
several
short
term
in
vitro/
in
vivo
assays,
including
a
bacterial
reverse
mutation
assay
(
Ames
test),
an
in
vitro
mammalian
point
mutation
assay
in
Chinese
hamster
ovary
cells,
an
in
vitro
cytogenetics
assay
in
human
lymphocytes
and
an
in
vivo
mouse
micronucleus
assay
following
inhalation
exposure.
In
addition,
1
MCP
is
not
mutagenic
when
tested
as
a
suspension
in
cell
media
in
the
Ames
test
and
in
the
in
vitro
mouse
lymphoma
forward
mutation
assay
(
MRID
444647
10)
and
is
not
mutagenic
in
the
in
vivo
mouse
micronucleus
assay
(
MRID
444747
11)
following
oral
exposure
(
gavage).
3.
Developmental
toxicity
(
MRID
454586
08).
1
MCP
produces
no
developmental
toxicity
when
tested
in
a
standard
developmental
toxicity
study
in
the
rat
via
inhalation
at
concentrations
up
to
and
including
2.3
mg
a.
i./
L
(
or
543
mg
a.
i./
kg/
day,
6
hr
exposure/
day).
The
no
observed
adverse
effect
level
(
NOAEL)
for
maternal
toxicity
was
0.24
mg
a.
i./
L
(
56
mg
a.
i./
kg/
day,
6
hr
exposure/
day).
4.
Subchronic
toxicity
(
MRID
456090
01).
1
MCP
was
tested
in
a
90
day
inhalation
study
at
doses
of
0.05,
0.24
and
2.3
mg
a.
i./
kg
in
the
rat.
The
NOAEL
is
0.05
mg
a.
i./
L
(
equivalent
to
9
to
15
mg
a.
i./
kg/
day),
based
on
minimal
to
mild
effects
on
spleen
and
kidney
histopathology
at
0.24
mg
a.
i./
L
(
equivalent
to
39
to
66
mg
a.
i./
kg/
day).
In
this
study
there
was
no
evidence
of
neurotoxicity,
no
effects
on
the
respiratory
tract
and
no
effects
on
pathology
of
any
endocrine
or
reproductive
organs
up
to
and
including
the
highest
dose
tested
of
2.3
mg
a.
i./
L
(
or
equivalent
to
380
to
640
mg
a.
i./
kg/
day).
5.
AgroFresh
(
the
applicant)
submitted
a
waiver
request
for
the
immune
response
data
requirements
based
on
the
current
toxicological
data
submitted
on
1
MCP.
The
review
of
the
3
month
inhalation
rat
study
(
mentioned
in
the
previous
paragraph)
indicates,
no
effects
on
thymus
weight
and
no
effects
on
the
histopathology
of
the
thymus,
bone
marrow
or
spleen
that
would
be
attributed
to
an
impact
on
the
immune
system
were
seen.
There
were
no
effects
on
white
blood
cell
differential
parameters
(
including
monocytes,
lymphocytes,
segmented
neutrophils
or
eosinophils)
and
no
basophils
were
observed
which
may
be
indicative
of
an
allergic
reaction.
The
Agency
concluded
that
1
MCP
did
not
induce
dysfunction
or
inappropriate
suppressive
responses
in
components
of
the
immune
system.
As
a
result,
immune
response
data
requirements
were
waived.
6.
Other.
1
MCP
has
a
mode
of
action
in
plants
which
is
a
non
persistent
and
non
toxic
mode
of
action.
1
MCP
prevents
the
natural
chemical,
ethylene,
from
binding
to
ethylene
receptors
in
plants.
This
mode
of
action
is
not
relevant
in
animals,
since
ethylene
receptors
are
not
present
in
animal
tissues.
IV.
Aggregate
Exposures
In
examining
aggregate
exposure,
FFDCA
section
408
directs
EPA
to
consider
available
information
concerning
exposures
from
the
pesticide
residue
in
food
and
all
other
nonoccupational
exposures,
including
drinking
water
from
ground
water
or
surface
water
and
exposure
through
pesticide
use
in
gardens,
lawns,
or
buildings
(
residential
and
other
indoor
uses).
A.
Dietary
Exposure
1.
Food
From
food
and
feed
uses.
The
primary
source
for
human
exposure
to
1
MCP
will
be
from
ingestion
of
the
following
raw
food
commodities
and
the
processed
food
commodities
derived
from:
apples,
melons,
tomatoes,
pears,
avocadoes,
mangoes,
papayas,
kiwifruit,
plums,
apricots
and
persimmons.
Studies
submitted
(
MRID
456090
02)
showed
residues
in
treated
apples
to
be
extremely
low
(
average
residue
was
0.004
ppm
using
an
exaggerated
treatment
rate
of
1,200
parts
per
billion
(
ppb)
versus
the
1,000
ppb
proposed
label
rate).
A
worst
case
scenario
(
using
the
0.004
ppm
average
residue
concentration
found
in
treated
apples
and
assuming
that
concentration
is
present
in
100%
of
the
diet
regardless
of
crops
treated)
indicates
that
a
daily
diet
of
1.5
kg/
day
could
contain
0.006
mg
1
MCP.
For
the
general
population
(
assuming
an
average
body
weight
of
60
kg),
this
would
represent
a
daily
intake
of
0.0001
mg
1
MCP/
kg
body
weight
which
is
90,000
to
150,000
fold
less
than
the
9
15
mg/
kg
NOAEL
indicated
in
the
90
day
inhalation
study.
Residues
in
other
treated
commodities
are
expected
to
be
similar
or
even
lower
since
the
highest
treatment
rate
is
recommended
for
apples.
Processing
would
be
expected
to
further
lower
the
residue
levels
in
processed
food
commodities.
2.
Drinking
water
exposure.
Since
1
MCP
will
only
be
used
on
postharvested
fruits
and
vegetables
in
enclosed
storage
areas,
there
is
little
if
any,
potential
for
drinking
water
exposure.
B.
Other
Non
Occupational
Exposure
The
potential
for
non
dietary
exposure
to
1
MCP
for
the
general
population,
is
unlikely
because
potential
use
sites
are
commercial,
agricultural,
and
horticultural.
1
MCP
is
currently
registered
for
indoor,
nonfood
commercial
use
on
flowers
and
ornamentals.
The
Agency
has
approved
that
use,
based
on
the
data
submitted
that
show
little
potential
for
significant
non
occupational
exposure
to
the
general
population.
1.
Dermal
exposure.
1
MCP
will
only
be
sold
enclosed
in
a
generator
for
treatment
of
raw
agricultural
commodities.
The
generator
will
not
release
1
MCP
until
the
applicator
has
exited
the
storage
area
and
entrances
to
the
treatment
area
have
been
sealed.
At
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Federal
Register
/
Vol.
67,
No.
144
/
Friday,
July
26,
2002
/
Rules
and
Regulations
the
end
of
the
treatment
period,
the
storage
area
will
be
vented
before
workers
are
permitted
to
reenter
the
area.
This
label
mitigating
language
would
eliminate
the
potential
for
dermal
exposure
to
handlers
or
applicators.
2.
Inhalation
exposure.
As
mentioned
in
the
previous
paragraph,
the
use
of
this
product
according
to
the
label
instructions
would
result
in
little,
if
any,
inhalation
exposure
to
handlers
or
applicators.
V.
Cumulative
Effects
The
Agency
has
considered
the
cumulative
effects
of
1
MCP
and
other
substances
in
relation
to
a
common
mechanism
of
toxicity.
These
considerations
include
the
possible
cumulative
effects
of
such
residues
on
infants
and
children.
There
is
no
indication
of
mammalian
toxicity
at
the
maximum
doses
tested,
of
this
or
other
products
containing
1
MCP.
VI.
Determination
of
Safety
for
U.
S.
Population,
Infants
and
Children
1.
U.
S.
population.
There
is
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
residues
of
1
MCP
to
the
U.
S.
population.
This
includes
all
anticipated
dietary
exposures
and
all
other
exposures
for
which
there
is
reliable
information.
The
Agency
has
arrived
at
this
conclusion
based
on
the
very
low
levels
of
mammalian
toxicity
(
no
toxicity
at
the
maximum
doses
tested,
Toxicity
Categories
III
and
IV)
and
the
minimum
exposure
associated
with
1
MCP's
use.
2.
Infants
and
children.
FFDCA
section
408
provides
that
EPA
shall
apply
an
additional
tenfold
margin
of
exposure
(
safety)
for
infants
and
children
in
the
case
of
threshold
effects
to
account
for
prenatal
and
postnatal
toxicity
and
the
completeness
of
the
data
base
unless
EPA
determines
that
a
different
margin
of
exposure
(
safety)
will
be
safe
for
infants
and
children.
Margins
of
exposure
(
safety)
are
often
referred
to
as
uncertainty
(
safety)
factors.
In
this
instance,
based
on
all
the
available
information,
the
Agency
concludes
that
1
MCP
is
practically
non
toxic
to
mammals,
including
infants
and
children.
Thus,
there
are
no
threshold
effects
of
concern
and,
as
a
result
the
provision
requiring
an
additional
margin
of
safety
does
not
apply.
Further,
based
on
the
lack
of
observed
developmental
toxicity
and
extremely
low
exposure,
there
is
reasonable
certainty
that
no
harm
to
infants,
children,
or
adults
will
result
from
aggregate
exposure
to
1
MCP
residues.
Exemption
of
1
MCP
from
the
requirements
of
a
tolerance
should
pose
no
significant
risk
to
humans
or
the
environment
VII.
Other
Considerations
A.
Endocrine
Disruptors
EPA
is
required
under
the
FFDCA
as
amended
by
FQPA
to
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
``
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate.''
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
is
no
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program(
EDSP).
When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
Endocrine
Disruptor
Screening
Program
have
been
developed,
1
MCP
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.
Based
on
available
data,
no
endocrine
system
related
effects
have
been
identified
with
consumption
of
1
MCP.
In
addition,
1
MCP
does
not
share
any
structural
similarity
to
any
known
endocrine
disruptive
chemical.
B.
Analytical
Method(
s)
EPA
is
establishing
an
exemption
from
the
requirement
of
a
tolerance
without
any
numerical
limitation
for
the
reasons
stated
above,
including
1
MCP's
lack
of
mammalian
toxicity.
For
the
same
reasons,
the
Agency
has
concluded
that
an
analytical
method
is
not
required
for
enforcement
purposes
for
1
MCP.
C.
Codex
Maximum
Residue
Level
No
Codex
maximum
residue
levels
are
established
for
residues
of
1
MCP
in
or
on
any
food
or
feed
crop.
There
are
no
established
tolerances
or
exemptions
from
tolerance
for
1
MCP
in
the
United
States.
The
Agency
has
classified
1
MCP
as
a
biochemical
pesticide.
VIII.
Conclusions
Based
on
the
toxicology
data
submitted,
there
is
reasonable
certainty
no
harm
will
result
from
aggregate
exposure
of
residues
of
1
MCP
to
the
U.
S.
population,
including
infants
and
children,
when
the
proposed
product
is
used
in
accordance
with
label
instructions
and
good
agricultural
practices.
This
includes
all
anticipated
dietary
exposures
and
all
other
exposures
for
which
reliable
data
were
submitted,
accepted
and
reviewed.
The
Agency
has
arrived
at
this
conclusion
based
on
the
data
submitted
demonstrating
no
toxicity
at
the
maximum
doses
tested.
As
a
result,
EPA
establishes
an
exemption
from
tolerance
requirements
pursuant
to
FFDCA
408(
c)
and
(
d)
for
residues
of
1
MCP
in
or
on
all
food
commodities.
IX.
Objections
and
Hearing
Requests
Under
section
408(
g)
of
the
FFDCA,
as
amended
by
the
FQPA,
any
person
may
file
an
objection
to
any
aspect
of
this
regulation
and
may
also
request
a
hearing
on
those
objections.
The
EPA
procedural
regulations
which
govern
the
submission
of
objections
and
requests
for
hearings
appear
in
40
CFR
part
178.
Although
the
procedures
in
those
regulations
require
some
modification
to
reflect
the
amendments
made
to
the
FFDCA
by
the
FQPA
of
1996,
EPA
will
continue
to
use
those
procedures,
with
appropriate
adjustments,
until
the
necessary
modifications
can
be
made.
The
new
section
408(
g)
provides
essentially
the
same
process
for
persons
to
``
object''
to
a
regulation
for
an
exemption
from
the
requirement
of
a
tolerance
issued
by
EPA
under
new
section
408(
d),
as
was
provided
in
the
old
FFDCA
sections
408
and
409.
However,
the
period
for
filing
objections
is
now
60
days,
rather
than
30
days.
A.
What
Do
I
Need
to
Do
to
File
an
Objection
or
Request
a
Hearing?
You
must
file
your
objection
or
request
a
hearing
on
this
regulation
in
accordance
with
the
instructions
provided
in
this
unit
and
in
40
CFR
part
178.
To
ensure
proper
receipt
by
EPA,
you
must
identify
docket
ID
number
OPP
2002
0142
in
the
subject
line
on
the
first
page
of
your
submission.
All
requests
must
be
in
writing,
and
must
be
mailed
or
delivered
to
the
Hearing
Clerk
on
or
before
September
24,
2002.
1.
Filing
the
request.
Your
objection
must
specify
the
specific
provisions
in
the
regulation
that
you
object
to,
and
the
grounds
for
the
objections
(
40
CFR
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Federal
Register
/
Vol.
67,
No.
144
/
Friday,
July
26,
2002
/
Rules
and
Regulations
178.25).
If
a
hearing
is
requested,
the
objections
must
include
a
statement
of
the
factual
issues(
s)
on
which
a
hearing
is
requested,
the
requestor's
contentions
on
such
issues,
and
a
summary
of
any
evidence
relied
upon
by
the
objector
(
40
CFR
178.27).
Information
submitted
in
connection
with
an
objection
or
hearing
request
may
be
claimed
confidential
by
marking
any
part
or
all
of
that
information
as
CBI.
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
A
copy
of
the
information
that
does
not
contain
CBI
must
be
submitted
for
inclusion
in
the
public
record.
Information
not
marked
confidential
may
be
disclosed
publicly
by
EPA
without
prior
notice.
Mail
your
written
request
to:
Office
of
the
Hearing
Clerk
(
1900),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460.
You
may
also
deliver
your
request
to
the
Office
of
the
Hearing
Clerk
in
Rm.
C400,
Waterside
Mall,
401
M
St.,
SW.,
Washington,
DC
20460.
The
Office
of
the
Hearing
Clerk
is
open
from
8
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
telephone
number
for
the
Office
of
the
Hearing
Clerk
is
(
202)
260
4865.
2.
Tolerance
fee
payment.
If
you
file
an
objection
or
request
a
hearing,
you
must
also
pay
the
fee
prescribed
by
40
CFR
180.33(
i)
or
request
a
waiver
of
that
fee
pursuant
to
40
CFR
180.33(
m).
You
must
mail
the
fee
to:
EPA
Headquarters
Accounting
Operations
Branch,
Office
of
Pesticide
Programs,
P.
O.
Box
360277M,
Pittsburgh,
PA
15251.
Please
identify
the
fee
submission
by
labeling
it
``
Tolerance
Petition
Fees.''
EPA
is
authorized
to
waive
any
fee
requirement
``
when
in
the
judgement
of
the
Administrator
such
a
waiver
or
refund
is
equitable
and
not
contrary
to
the
purpose
of
this
subsection.''
For
additional
information
regarding
the
waiver
of
these
fees,
you
may
contact
James
Tompkins
by
phone
at
(
703)
305
5697,
by
e
mail
at
tompkins.
jim@
epa.
gov,
or
by
mailing
a
request
for
information
to
Mr.
Tompkins
at
Registration
Division
(
7505C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460.
If
you
would
like
to
request
a
waiver
of
the
tolerance
objection
fees,
you
must
mail
your
request
for
such
a
waiver
to:
James
Hollins,
Information
Resources
and
Services
Division
(
7502C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460.
3.
Copies
for
the
Docket.
In
addition
to
filing
an
objection
or
hearing
request
with
the
Hearing
Clerk
as
described
in
Unit
IX.
A.,
you
should
also
send
a
copy
of
your
request
to
the
PIRIB
for
its
inclusion
in
the
official
record
that
is
described
in
Unit
I.
B.
2.
Mail
your
copies,
identified
by
docket
ID
number
OPP
2002
0142,
to:
Public
Information
and
Records
Integrity
Branch,
Information
Resources
and
Services
Division
(
7502C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460.
In
person
or
by
courier,
bring
a
copy
to
the
location
of
the
PIRIB
described
in
Unit
I.
B.
2.
You
may
also
send
an
electronic
copy
of
your
request
via
e
mail
to:
oppdocket
epa.
gov.
Please
use
an
ASCII
file
format
and
avoid
the
use
of
special
characters
and
any
form
of
encryption.
Copies
of
electronic
objections
and
hearing
requests
will
also
be
accepted
on
disks
in
WordPerfect
6.1/
8.0
or
ASCII
file
format.
Do
not
include
any
CBI
in
your
electronic
copy.
You
may
also
submit
an
electronic
copy
of
your
request
at
many
Federal
Depository
Libraries.
B.
When
Will
the
Agency
Grant
a
Request
for
a
Hearing?
A
request
for
a
hearing
will
be
granted
if
the
Administrator
determines
that
the
material
submitted
shows
the
following:
There
is
a
genuine
and
substantial
issue
of
fact;
there
is
a
reasonable
possibility
that
available
evidence
identified
by
the
requestor
would,
if
established
resolve
one
or
more
of
such
issues
in
favor
of
the
requestor,
taking
into
account
uncontested
claims
or
facts
to
the
contrary;
and
resolution
of
the
factual
issues(
s)
in
the
manner
sought
by
the
requestor
would
be
adequate
to
justify
the
action
requested
(
40
CFR
178.32).
X.
Regulatory
Assessment
Requirements
This
final
rule
establishes
an
exemption
from
the
tolerance
requirement
under
FFDCA
section
408(
d)
in
response
to
a
petition
submitted
to
the
Agency.
The
Office
of
Management
and
Budget
(
OMB)
has
exempted
these
types
of
actions
from
review
under
Executive
Order
12866,
entitled
Regulatory
Planning
and
Review
(
58
FR
51735,
October
4,
1993).
Because
this
rule
has
been
exempted
from
review
under
Executive
Order
12866
due
to
its
lack
of
significance,
this
rule
is
not
subject
to
Executive
Order
13211,
Actions
Concerning
Regulations
That
Significantly
Affect
Energy
Supply,
Distribution,
or
Use
(
66
FR
28355,
May
22,
2001).
This
final
rule
does
not
contain
any
information
collections
subject
to
OMB
approval
under
the
Paperwork
Reduction
Act
(
PRA),
44
U.
S.
C.
3501
et
seq.,
or
impose
any
enforceable
duty
or
contain
any
unfunded
mandate
as
described
under
Title
II
of
the
Unfunded
Mandates
Reform
Act
of
1995
(
UMRA)
(
Public
Law
104
4).
Nor
does
it
require
any
special
considerations
under
Executive
Order
12898,
entitled
Federal
Actions
to
Address
Environmental
Justice
in
Minority
Populations
and
Low
Income
Populations
(
59
FR
7629,
February
16,
1994);
or
OMB
review
or
any
Agency
action
under
Executive
Order
13045,
entitled
Protection
of
Children
from
Environmental
Health
Risks
and
Safety
Risks
(
62
FR
19885,
April
23,
1997).
This
action
does
not
involve
any
technical
standards
that
would
require
Agency
consideration
of
voluntary
consensus
standards
pursuant
to
section
12(
d)
of
the
National
Technology
Transfer
and
Advancement
Act
of
1995
(
NTTAA),
Public
Law
104
113,
section
12(
d)
(
15
U.
S.
C.
272
note).
Since
tolerances
and
exemptions
that
are
established
on
the
basis
of
a
petition
under
FFDCA
section
408(
d),
such
as
the
tolerance
exemption
in
this
final
rule,
do
not
require
the
issuance
of
a
proposed
rule,
the
requirements
of
the
Regulatory
Flexibility
Act
(
RFA)
(
5
U.
S.
C.
601
et
seq.)
do
not
apply.
In
addition,
the
Agency
has
determined
that
this
action
will
not
have
a
substantial
direct
effect
on
States,
on
the
relationship
between
the
national
government
and
the
States,
or
on
the
distribution
of
power
and
responsibilities
among
the
various
levels
of
government,
as
specified
in
Executive
Order
13132,
entitled
Federalism
(
64
FR
43255,
August
10,
1999).
Executive
Order
13132
requires
EPA
to
develop
an
accountable
process
to
ensure
``
meaningful
and
timely
input
by
State
and
local
officials
in
the
development
of
regulatory
policies
that
have
federalism
implications.''
``
Policies
that
have
federalism
implications''
is
defined
in
the
Executive
order
to
include
regulations
that
have
``
substantial
direct
effects
on
the
States,
on
the
relationship
between
the
national
government
and
the
States,
or
on
the
distribution
of
power
and
responsibilities
among
the
various
levels
of
government.''
This
final
rule
directly
regulates
growers,
food
processors,
food
handlers
and
food
retailers,
not
States.
This
action
does
not
alter
the
relationships
or
distribution
of
power
and
responsibilities
established
by
Congress
in
the
preemption
provisions
of
FFDCA
section
408(
n)(
4).
For
these
same
reasons,
the
Agency
has
determined
that
this
rule
does
not
have
any
``
tribal
implications
''
as
described
in
Executive
Order
13175,
entitled
Consultation
and
Coordination
with
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Federal
Register
/
Vol.
67,
No.
144
/
Friday,
July
26,
2002
/
Rules
and
Regulations
Indian
Tribal
Governments
(
65
FR
67249,
November
6,
2000).
Executive
Order
13175,
requires
EPA
to
develop
an
accountable
process
to
ensure
``
meaningful
and
timely
input
by
tribal
officials
in
the
development
of
regulatory
policies
that
have
tribal
implications.''
``
Policies
that
have
tribal
implications''
is
defined
in
the
Executive
order
to
include
regulations
that
have
``
substantial
direct
effects
on
one
or
more
Indian
tribes,
on
the
relationship
between
the
Federal
Government
and
the
Indian
tribes,
or
on
the
distribution
of
power
and
responsibilities
between
the
Federal
Government
and
Indian
tribes.''
This
rule
will
not
have
substantial
direct
effects
on
tribal
governments,
on
the
relationship
between
the
Federal
Government
and
Indian
tribes,
or
on
the
distribution
of
power
and
responsibilities
between
the
Federal
government
and
Indian
tribes,
as
specified
in
Executive
Order
13175.
Thus,
Executive
Order
13175
does
not
apply
to
this
rule.
XI.
Submission
to
Congress
and
the
Comptroller
General
The
Congressional
Review
Act,
5
U.
S.
C.
801
et
seq.,
as
added
by
the
Small
Business
Regulatory
Enforcement
Fairness
Act
of
1996,
generally
provides
that
before
a
rule
may
take
effect,
the
agency
promulgating
the
rule
must
submit
a
rule
report,
which
includes
a
copy
of
the
rule,
to
each
House
of
the
Congress
and
to
the
Comptroller
General
of
the
United
States.
EPA
will
submit
a
report
containing
this
rule
and
other
required
information
to
the
U.
S.
Senate,
the
U.
S.
House
of
Representatives,
and
the
Comptroller
General
of
the
United
States
prior
to
publication
of
this
final
rule
in
the
Federal
Register.
This
final
rule
is
not
a
``
major
rule''
as
defined
by
5
U.
S.
C.
804(
2).
List
of
Subjects
in
40
CFR
Part
180
Environmental
protection,
Administrative
practice
and
procedure,
Agricultural
commodities,
Pesticides
and
pests,
Reporting
and
recordkeeping
requirements.
Dated:
July
16,
2002.
Marcia
E.
Mulkey,
Director,
Office
of
Pesticide
Programs.
Therefore,
40
CFR
chapter
I
is
amended
as
follows:
PART
180
[
AMENDED]
1.
The
authority
citation
for
part
180
continues
to
read
as
follows:
Authority:
21
U.
S.
C.
321(
q),
346(
a)
and
374.
2.
Section
180.1220
is
added
to
subpart
D
to
read
as
follows:
§
180.1220
1
Methylcyclopropene;
exemption
from
the
requirement
of
a
tolerance.
An
exemption
from
the
requirement
of
a
tolerance
is
established
for
residues
of
1
Methylcyclopropene
in
or
on
fruits
and
vegetables
when
used
as
a
post
harvest
plant
growth
regulator,
i.
e.,
for
the
purpose
of
inhibiting
the
effects
of
ethylene.
[
FR
Doc.
02
18868
Filed
7
25
02;
8:
45am]
BILLING
CODE
6560
50
S
DEPARTMENT
OF
HEALTH
AND
HUMAN
SERVICES
Centers
for
Medicare
&
Medicaid
Services
42
CFR
Part
405
[
CMS
3074
F2]
RIN
0938
AK98
Medicare
Program;
End
Stage
Renal
Disease:
Removing
of
Waiver
of
Conditions
for
Coverage
Under
a
State
of
Emergency
in
the
Houston,
Texas
Area
AGENCY:
Centers
for
Medicare
&
Medicaid
Services
(
CMS).
ACTION:
Final
rule.
SUMMARY:
This
final
rule
removes
an
emergency
waiver
of
the
Medicare
endstage
renal
disease
(
ESRD)
conditions
for
coverage
granted
to
permit
the
transplant
team
of
an
approved
renal
transplant
center
to
furnish
kidney
transplant
services
in
three
specific
hospitals
in
the
Houston,
Texas
area
during
a
state
of
emergency.
The
state
of
emergency
has
ceased,
the
primary
kidney
transplant
center
in
the
area
is
now
fully
operational,
and
the
effective
period
of
the
waiver
provisions
has
expired.
EFFECTIVE
DATE:
July
26,
2002.
FOR
FURTHER
INFORMATION
CONTACT:
Rachael
Weinstein,
(
410)
786
6775
SUPPLEMENTARY
INFORMATION
I.
Provisions
of
This
Rule
On
June
20,
2001,
we
published
a
final
rule
in
the
Federal
Register
(
66
FR
33030
33031)
that
granted
an
emergency
waiver
of
the
Medicare
endstage
renal
disease
(
ESRD)
conditions
of
coverage
to
permit
the
transplant
team
of
an
approved
renal
transplant
center
to
furnish
covered
kidney
transplant
services
in
three
specific
hospitals
in
the
Houston,
Texas
area
during
a
state
of
emergency.
The
state
of
emergency
(
a
natural
disaster
due
to
flooding)
resulted
in
a
severe
health
and
safety
threat
to
hospitals
in
the
entire
Houston,
Texas
area,
including
ESRD
facilities
that
were
approved
to
furnish
kidney
transplant
services.
Waivers
of
the
conditions
of
coverage
were
granted
to
Memorial
Hermann
Memorial
City
Hospital,
Memorial
Hermann
Southwest
Hospital,
and
Memorial
Hermann
Southeast
Hospital
to
permit
an
approved
transplant
team
to
furnish
kidney
transplant
services
in
the
three
hospitals,
effective
June
15,
2001,
through
the
earlier
of
December
15,
2001,
or
until
Memorial
Hermann
Hospital,
the
primary
kidney
transplant
center,
reopened.
Memorial
Hermann
Hospital
is
now
reopened.
In
the
June
20,
2001
final
rule,
we
amended
the
Medicare
regulations
to
include
a
new
§
405.2175
that
incorporated
the
waiver
provisions.
In
§
405.2175,
we
specified
that
we
would
publish
a
rule
removing
the
waiver
provisions
from
the
regulations
after
the
waiver
expired.
The
waiver
has
expired
and
we
are
removing
the
provisions
from
the
Medicare
regulations.
II.
Waiver
of
Proposed
Rulemaking
and
Delay
of
Effective
Date
We
ordinarily
publish
a
notice
of
proposed
rulemaking
in
the
Federal
Register
and
invite
public
comment
on
a
proposed
rule.
The
notice
of
proposed
rulemaking
includes
a
reference
to
the
legal
authority
under
which
the
rule
is
proposed,
and
the
terms
and
substances
of
the
proposed
rule
or
a
description
of
the
subjects
and
issues
involved.
This
procedure
can
be
waived,
however,
if
an
agency
finds
good
cause
that
a
noticeand
comment
procedure
is
impracticable,
unnecessary,
or
contrary
to
the
public
interest
and
incorporates
a
statement
of
the
findings
and
its
reasons
in
the
rule
issued.
Further,
we
generally
provide
for
final
rules
to
be
effective
no
sooner
than
30
days
after
the
date
of
publication
unless
we
find
good
cause
under
5
U.
S.
C.
553(
d)(
3)
to
waive
the
30
day
delay
of
the
effective
date.
The
purpose
of
the
30
day
waiting
period
between
publication
of
an
administrative
agency
final
rule
and
its
effective
date
is
to
give
affected
parties
reasonable
time
to
adjust
their
behavior
before
the
final
rule
takes
place.
The
state
of
emergency
under
which
we
granted
a
waiver
of
the
ESRD
conditions
of
coverage
is
now
over
in
the
Houston,
Texas
area,
and
Memorial
Hermann
Hospital
is
reopened
to
furnish
kidney
transplant
services.
We
announced
in
the
June
20,
2001
final
rule
our
intention
to
remove
the
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| epa | 2024-06-07T20:31:42.571802 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0142-0001/content.txt"
} |
EPA-HQ-OPP-2002-0146-0003 | Supporting & Related Material | "2002-06-25T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
SUBJECT:
TRED
for
Tebuthiuron
(Chemical
#
105501,
DP
Barcode
D279066)
FROM:
Mark
Corbin,
Environmental
Scientist
Environmental
Risk
Branch
1
Environmental
Fate
and
Effects
Division
(7507C)
THRU:
Dana
Spatz,
Acting
Branch
Chief
Environmental
Risk
Branch
1
Environmental
Fate
and
Effects
Division
(7507C)
TO:
Daniel
Helfgot
Special
Review
Branch
Special
Review
and
Reregistration
Division
(7508C)
Wilhelmena
Livingston
Special
Review
Branch
Special
Review
and
Reregistration
Division
(7508C)
EFED
has
completed
a
drinking
water
assessment
for
the
reassessment
of
tolerances
for
the
herbicide
Tebuthiuron.
This
assessment
considers
Tebuthiuron,
and
to
the
extent
possible,
the
degradate
"Compound
104,"
which
the
Health
Effects
Division
has
determined
is
of
toxicological
concern.
Compound
104
was
the
only
degradate
of
Tebuthiuron
of
toxicological
concern
that
was
detected
in
the
environmental
fate
studies
reviewed.
Tier
II
(PRZM
version
3.12/
EXAMS
version
2.97.5)
surface
water
modeling
for
Tebuthiuron
use
on
rangeland/
pasture
at
4
pounds
active
ingredient
per
acre
(lbs
ai/
A)
using
the
index
reservoir
predicts
the
1
in
10
year
annual
maximum
(acute)
concentration
of
15.1
:
g/
L.
The
1
in
10
year
annual
average
concentration
(non
cancer
chronic)
of
Tebuthiuron
is
predicted
to
be
1.5
:
g/
L
.
The
36
year
annual
average
concentration
(cancer
chronic)
of
Tebuthiuron
is
predicted
to
be
0.6
:
g/
L.
SCIGROW
(version
2.1)
modeling
estimates
the
acute
and
chronic
concentration
of
Tebuthiuron
residues
in
shallow
groundwater
is
181
:
g/
L.
Monitoring
data
was
evaluated
from
the
USGS
NAWQA
program
and
from
preliminary
data
from
the
USGS
Reservoir
Pilot
Monitoring
Project.
Both
surface
and
ground
water
data
from
the
NAWQA
program
were
evaluated
for
annual
maximum
(peak)
and
time
weighted
mean
concentrations.
Only
surface
water
data
was
available
from
the
USGS
Reservoir
Pilot
Monitoring
study
which
was
also
evaluated
for
annual
N
N
S
N
CH
3
CH
3
C
H
3
C
H
3
O
N
H
CH
3
maximum
and
time
weighted
mean
concentrations.
EFED
proposes
using
the
estimated
environmental
concentrations
(EECs)
from
modeling
as
upper
bound
estimates
of
exposure.
Acute
(annual
maximum)
concentrations
and
chronic
(time
weighted
mean)
concentrations
from
monitoring
data
are
summarized
below.
In
general
these
concentrations
are
less
than
the
estimates
from
modeling.
EFED
proposes
using
the
model
results
as
acute
and
chronic
EECs
for
the
risk
assessment
because
Tebuthiuron
is
persistent
and
data
from
edge
of
field
runoff
studies
conducted
in
the
1980's
indicate
concentrations
higher
than
those
found
in
the
NAWQA
and
USGS
Reservoir
studies
can
occur.
Drinking
water
environmental
concentrations
for
Compound
104
cannot
be
estimated
due
to
a
lack
of
fate
and
monitoring
data
.
Compound
104
was
detected
at
a
maximum
concentration
of
0.004
mg/
L
in
ground
water
in
a
Small
Scale
Retrospective
study
(MRID
42390901)
submitted
in
1992.
However
the
concentrations
were
detected
four
years
after
application
of
Tebuthiuron
and
may
not
be
representative
of
the
maximum
concentrations
present
beneath
the
site
after
application.
Compound
104
was
detected
at
6.9%
of
applied
parent
at
the
end
of
the
aerobic
soil
metabolism
study
but
was
noted
to
still
be
increasing
at
the
end
of
the
study.
It
is
suspected
that
the
percent
applied
of
Compound
104
would
have
increased
if
the
experiment
had
run
longer.
Compound
104
appears
to
have
similar
mobility
to
Tebuthiuron
and
has
a
long
half
life.
Therefore,
EFED
is
unable
to
estimate
how
much
degradate
might
have
been
produced
if
the
study
had
run
longer.
Introduction
Tebuthiuron
is
a
non
selective
herbicide
used
primarily
on
pastureland,
rights
of
way,
and
other
non
agricultural
sites.
Tebuthiuron
is
used
predominantly
in
Texas,
Oklahoma,
and
New
Mexico
based
on
information
provided
by
the
registrant
and
BEAD.
Information
on
publically
supplied
drinking
water
available
from
the
USGS
(Selley,
et
al,
1998;
"Estimated
Use
of
Water
in
the
United
States
in
1995".
USGS
Circular
1200)
was
reviewed.
Both
surface
and
ground
water
sources
are
used
for
publically
supplied
water
in
Texas,
Oklahoma
and
New
Mexico.
Ground
water
provides
approximately
89%
of
New
Mexico's
public
water,
while
surface
water
provides
66%
and
83%
of
public
water
to
Texas
and
Oklahoma
respectively.
Reviewing
population
served
information
indicates
that
88%
of
New
Mexico's
population
relies
on
ground
water
while
58%
of
Texas
and
74%
of
Oklahoma's
population
rely
on
surface
water.
Chemical
Name:
N[
5(
1,1
dimethylethyl)
1,3,4
thiadiazol
2
yl]
N,
N'
dimethylurea
Compound
104:
N[
5(
1,1
dimethylethyl)
1,3,4
thiadiazol
2
yl]
N
methylurea
Chemical
Structure:
Environmental
Fate
As
reported
in
the
1994
RED
Tebuthiuron
is
persistent
and
mobile,
and
that
the
"principal
route
of
dissipation
appears
to
be
transport
to
ground
and
surface
water."
This
assessment
was
based
on
a
suite
of
required
environmental
fate
studies
that
lacked
only
a
field
dissipation
study.
This
study
has
since
been
submitted
and
reviewed
and
found
to
be
marginally
acceptable
with
field
dissipation
half
lives
of
385
days
(Florida),
770
days
(California),
and
575
days
(Nebraska).
The
quickest
observed
route
of
Tebuthiuron
degradation
in
laboratory
studies
was
soil
photolysis
(half
life
39.7
days.)
Tebuthiuron
is
stable
in
laboratory
studies
to
hydrolysis,
aqueous
photolysis,
and
aerobic
aquatic
metabolism.
Tebuthiuron
was
also
stable
during
a
9
month
aerobic
soil
metabolism
study,
with
a
calculated
half
life
of
35.4
months.
Soil
partition
coefficients
(Kd)
from
adsorption/
desorption
studies
were
0.11,
0.62,
0.82
and
1.82,
indicating
that
Tebuthiuron
is
very
mobile
over
a
range
of
soil
types.
The
corresponding
Koc
values
relating
to
these
studies
ranged
from
31
to
151,
with
a
median
of
76
l/
kg.
The
soil
adsorption
of
Tebuthiuron
appears
to
be
related
to
the
amount
of
organic
carbon
in
the
soil.
Degradate
104
(Compound
104
was
the
only
degradate
of
Tebuthiuron
of
toxicological
concern
that
was
detected
in
the
environmental
fate
studies
reviewed)
was
at
6.9%
and
rising
by
the
end
of
the
study.
That
is
the
highest
concentration
of
any
degradate
in
any
lab
study.
Based
on
data
reviewed
at
the
time
of
the
RED,
the
degradate
appears
to
have
similar
mobility
to
parent
Tebuthiuron.
For
full
details
of
the
environmental
fate
assessment
for
Tebuthiuron,
see
the
1994
Reregistration
Eligibility
Document,
which
can
be
found
on
the
internet
at
http://
www.
epa.
gov/
pesticides/
reregistration/
status.
htm.
SURFACE
WATER
MONITORING
DATA
ASSESSMENT
National
NAWQA
Data
The
United
States
Geological
Survey
(USGS)
is
collecting
surface
and
ground
water
data
from
selected
watersheds
in
order
to
catalog
the
quality
of
water
resources
in
the
United
States.
The
National
Water
Quality
Assessment
(NAWQA)
program
began
in
1991
and
consists
of
chemical,
biological
and
physical
water
quality
data
from
59
study
units
across
the
United
States.
EFED
evaluated
the
occurrence
of
Tebuthiuron
in
surface
water
from
the
national
data
set.
Tebuthiuron
was
detected
in
surface
water
from
locations
in
30
states.
Compared
with
current
usage
which
is
predominantly
located
in
Texas,
Oklahoma,
and
New
Mexico,
the
occurrence
in
so
many
locations
is
reflective
of
past
usage
due
to
the
persistence
of
Tebuthiuron.
Tebuthiuron
was
detected
above
the
limit
of
detection
in
1155
samples
from
a
total
national
dataset
of
6625
samples
(17.4%).
This
rate
of
detection
is
greater
than
for
most
pesticides
included
as
analytes,
in
spite
of
its
limited
use.
EFED
analyzed
the
occurrence
of
Tebuthiuron
in
surface
water
from
each
sampling
location
within
each
state
on
an
annual
basis.
Each
year
of
data
from
an
individual
sample
location
was
evaluated
and
the
annual
maximum
concentration
and
time
weighted
mean
were
calculated.
For
the
purposes
of
this
assessment
only
the
upper
bound
time
weighted
mean
concentration
from
the
NAWQA
data
is
presented.
The
upper
bound
annual
time
weighted
mean
concentrations
were
estimated
by
setting
detections
at
or
below
the
detection
limit
at
the
value
of
the
detection
limit.
Analysis
of
the
national
NAWQA
surface
water
data
set
for
Tebuthiuron
is
presented
below.
The
annual
maximum
concentrations
ranged
from
2.83
to
0.003
(estimated
below
limit
of
quantitation)
:
g/
L
and
the
upper
bound
time
weighted
means
ranged
from
0.26
to
0.00
:
g/
L.
No
degradate
data
was
available
in
this
dataset
for
analysis.
The
annual
maximum
concentrations
and
time
weighted
mean
concentrations
were
ranked
and
percentiles
generated
for
the
dataset.
The
results
of
the
analysis
are
summarized
in
Table
1.
Table
1
Summary
of
Percentiles
for
Surface
Water
Annual
Maximum
and
Time
Weighted
Mean
Tebuthiuron
Concentrations
from
the
National
NAWQA
Data.
Percentile
National
NAWQA
Annual
Maximum
(
:
g/
L)
National
NAWQA
Time
Weighted
Mean
(
:
g/
L)
Maximum
2.
83
0.
26
99.9%
1.99
0.24
99%
0.21
0.06
95%
0.09
0.03
90%
0.06
0.02
50%
0.01
0.01
The
analysis
above
includes
the
entire
national
NAWQA
data
which
consists
of
surface
water
results
from
all
59
NAWQA
study
units.
In
order
to
assess
the
impact
of
high
Tebuthiuron
usage
on
the
analysis,
EFED
completed
an
additional
analysis
focusing
on
only
data
from
those
study
units
located
in
areas
of
high
Tebuthiuron
usage.
This
focused
assessment
is
intended
to
indicate
if
exposure
to
Tebuthiuron
in
surface
water
in
those
areas
where
the
herbicide
is
used
predominantly
(i.
e.
Texas,
Oklahoma,
and
New
Mexico)
is
greater
in
these
areas
than
on
a
national
basis.
The
study
units
for
the
focused
analysis
were
selected
by
overlaying
Tebuthiuron
usage
data
taken
from
registrant
supplied
information
with
the
NAWQA
study
units.
As
with
the
national
NAWQA,
the
focused
NAWQA
data
annual
maximum
concentrations
ranged
from
2.83
to
0.01
:
g/
L
and
the
upper
bound
time
weighted
means
ranged
from
0.26
to
0.01
:
g/
L.
No
degradate
data
was
available
in
this
dataset
for
analysis.
The
annual
maximum
concentrations
and
time
weighted
mean
concentrations
were
ranked
and
percentiles
generated
for
the
dataset.
The
results
of
the
analysis
are
summarized
in
Table
2.
Analysis
of
surface
water
data
from
those
locations
where
Tebuthiuron
usage
is
higher
indicates
that
while
the
range
of
concentrations
is
the
same
for
both
annual
maximum
and
time
weighted
mean,
the
concentrations
at
the
higher
percentiles
(>
90%)
are
higher
for
the
focused
data.
Table
2
Summary
of
Percentiles
for
Surface
Water
Annual
Maximum
and
Time
Weighted
Mean
Tebuthiuron
Concentrations
from
the
Focused
NAWQA
Data.
Percentile
Focused
NAWQA
Annual
Maximum
(
:
g/
L)
Focused
NAWQA
Time
Weighted
Mean
(
:
g/
L)
Maximum
2.
83
0.
26
99.9%
2.77
0.26
99%
2.27
0.25
95%
0.69
0.19
90%
0.33
0.05
50%
0.01
0.01
USGS
Reservoir
and
Finished
Water
Pilot
Monitoring
Study,
1999
2000
The
USGS
recently
issued
preliminary
data
from
a
cooperative
study
between
the
USGS
and
USEPA
for
"Pesticides
in
Water
supply
Reservoirs
and
Finished
Drinking
Water
A
Pilot
Monitoring
Program".
The
study
consists
of
the
analysis
of
samples
from
12
drinking
water
reservoirs
across
the
United
States
(including
Texas
and
Oklahoma).
EFED
has
reviewed
the
preliminary
data
for
the
occurrence
of
Tebuthiuron.
Tebuthiuron
was
analyzed
in
all
samples
using
the
same
analytical
methodology
as
the
USGS
NAWQA
program
(Schedule
2001).
Degradates
of
Tebuthiuron
were
not
analyzed
in
this
study.
Source
water
samples
were
collected
from
drinking
water
intakes
within
each
reservoir
and
treated
water
samples
were
collected
post
treatment.
Treated
and
intake
samples
were
typically
collected
on
the
same
date
within
several
hours
of
each
other.
In
addition,
samples
were
collected
and
analyzed
from
the
reservoir
outfall
(untreated)
from
selected
locations.
Several
outfall
locations
coincide
with
source
water
intakes
and
therefore
the
intake
and
outfall
samples
are
the
same.
Tebuthiuron
was
detected
in
232
out
of
627
analysis
for
a
detection
frequency
of
37%.
The
highest
peak
concentration
of
Tebuthiuron
was
0.032
:
g/
L
detected
in
the
treated
water
of
the
Oklahoma
Reservoir.
The
maximum
concentrations
and
time
weighted
mean
concentrations
were
calculated
for
each
subset
of
the
data
(intake,
treated,
and
outfall)
for
each
location.
The
results
are
presented
in
Table
3
and
4.
In
addition,
the
maximum
concentrations
and
time
weighted
mean
concentrations
were
ranked
and
percentiles
generated
for
the
data
set.
The
results
of
ranking
are
presented
in
Tables
5
and
6.
Table
3
Summary
of
Time
Weighted
Mean
Tebuthiuron
Concentrations
from
the
USGS
Reservoir
Data
from
1999
2000.
State
Intake
Sample
Time
Weighted
Mean
(
:
g/
L)
Treated
Sample
Time
Weighted
Mean
(
:
g/
L)
Reservoir
Outfall
Time
Weighted
Mean
(
:
g/
L)
SD
0.011
0.010
0.009
NY
0.010
0.011
OH
0.011
0.010
0.011
CA
0.009
0.010
TX
0.008
0.008
LA
0.010
0.010
0.010
NC
0.010
0.010
OK
0.018
0.020
0.011
MO
0.009
0.011
0.008
PA
0.008
0.008
SC
0.008
0.008
0.008
IN
0.011
0.011
0.006
Table
4
Summary
of
Maximum
Tebuthiuron
Concentrations
from
the
USGS
Reservoir
Data
from
1999
2000.
State
Intake
Sample
Maximum
(
:
g/
L)
Treated
Sample
Maximum
(
:
g/
L)
Reservoir
Outfall
Maximum
(
:
g/
L)
SD
0.016
0.016
0.010
NY
0.016
0.016
OH
0.015
0.010
0.012
CA
0.012
0.018
TX
0.010
0.010
LA
0.016
0.016
0.010
NC
0.011
0.010
OK
0.030
0.032
0.024
MO
0.010
0.016
0.010
PA
0.020
0.010
SC
0.010
0.016
0.010
IN
0.016
0.016
0.020
Table
5
Summary
of
Percentiles
for
Surface
Water
Annual
Time
Weighted
Mean
Tebuthiuron
Concentrations
from
the
USGS
Reservoir
Data
from
1999
2000.
Percentile
Time
Weighted
Mean
Concentration
from
Intake
Samples
(
:
g/
L)
Time
Weighted
Mean
Concentration
from
Treated
Samples
Time
Weighted
Mean
Concentration
from
Outfall
Samples
(
:
g/
L)
Maximum
0.
018
0.020
0.011
99.9%
0.018
0.020
0.011
99%
0.017
0.019
0.011
95%
0.014
0.015
0.011
90%
0.011
0.011
0.011
50%
0.010
0.010
0.009
Table
6
Summary
of
Percentiles
for
Surface
Water
Maximum
Tebuthiuron
Concentrations
from
the
USGS
Reservoir
Data
from
1999
2000.
Percentile
Maximum
Concentration
from
Intake
Samples
(
:
g/
L)
Maximum
Concentration
from
Treated
Samples
(
:
g/
L)
Maximum
Concentration
from
Outfall
Samples
(
:
g/
L)
Maximum
0.
030
0.032
0.024
99.9%
0.030
0.032
0.024
99%
0.029
0.030
0.024
95%
0.025
0.024
0.023
90%
0.020
0.018
0.022
50%
0.016
0.016
0.010
The
data
above
indicate
that
Tebuthiuron
is
found
at
a
high
frequency
of
detection
(greater
than
17%
in
NAWQA
data
and
greater
than
37%
in
the
USGS
Reservoir
data).
The
maximum
concentration
detected
in
these
two
studies
is
2.83
ppb
from
the
NAWQA
study.
Time
weighting
of
these
data
indicate
that
long
term
exposure
is
generally
less
than
1
ppb.
The
high
frequency
of
detection
is
likely
a
function
of
the
persistence
of
Tebuthiuron
in
the
environment.
The
low
concentrations
detected
(compared
with
edge
of
field
studies
discussed
below)
may
be
a
function
of
the
use
of
Tebuthiuron
which
is
focused
on
rangeland/
pasture
which
is
typically
in
arid
and
semi
arid
environments
and
is
not
likely
applied
in
proximity
to
surface
water
bodies
assessed
by
NAWQA
and
USGS
Reservoir
studies.
Additional
Monitoring
Data
Four
supplemental
watershed/
runoff
studies
were
conducted
in
Idaho,
Oklahoma,
Texas,
and
Arizona
between
1980
and
1984.
The
four
studies
represent
typical
application
scenarios
for
the
time
with
variable
rates
of
application
between
1
and
3
lbs
a.
i./
acre.
The
maximum
label
rate
is
4
lbs
a.
i./
acre
suggesting
that
these
studies
do
not
represent
a
worse
case
scenario.
Tebuthiuron
was
applied
to
varying
percentages
of
four
small
watersheds
ranging
between
13
acres
(Oklahoma)
to
303
acres
(Arizona).
Surface
water
and
"hydrosoil"
samples
were
collected
up
to
9
months
after
application
at
the
Idaho
site
(24
samples),
7
months
after
application
at
the
Oklahoma
site
(7
samples),
7
months
after
application
at
the
Texas
site
(6
samples),
and
3
months
after
application
at
the
Arizona
site
(53
samples).
Analytical
results
from
the
four
watershed/
runoff
studies
reported
concentrations
of
Tebuthiuron
in
surface
water
ranging
from
less
than
1
:
g/
L
(measured
at
the
conclusion
of
the
Texas
study)
up
to
180
:
g/
L
(measured
5/
5/
81
in
the
Oklahoma
study)
and
hydrosoil
residues
from
<
50
:
g/
L
up
to
140
:
g/
L.
EFED
revisited
the
analytical
data
from
the
four
runoff
studies
in
Idaho,
Oklahoma,
Texas,
and
Arizona.
Analysis
of
the
data
from
1980
through
1981
indicate
that
the
maximum
concentration
detected
for
each
site
respectively
is
180
:
g/
L
for
Oklahoma,
14
:
g/
L
for
Idaho,
70
:
g/
L
for
Texas,
and
54
:
g/
L
for
Arizona.
Time
weighted
mean
concentrations
were
calculated
for
each
dataset
with
the
results
showing
98
:
g/
L
in
Oklahoma,
7
:
g/
L
in
Idaho,
37
:
g/
L
in
Texas,
and
24
:
g/
L
in
Arizona.
These
concentrations
are
higher
than
those
observed
in
other
surface
water
monitoring
studies
(NAWQA
and
USGS
Reservoir
Pilot
Monitoring)
and
those
concentrations
predicted
using
PRZM/
EXAMS.
The
samples
analyzed
were
collected
from
catchment/
weir
ponds
within
a
watershed
unlike
the
other
surface
water
monitoring
data
which
is
generally
collected
from
flowing
streams
and
drinking
water
reservoirs.
The
concentrations
from
these
runoff
studies
are
better
compared
to
the
edge
of
field
effect
predicted
by
PRZM/
EXAMS.
The
comparison
with
PRZM/
EXAMS
suggests
that
the
modeling
may
under
predict
the
concentrations
that
would
be
expected
in
a
waterbody
adjacent
to
a
treatment
area.
GROUND
WATER
MONITORING
DATA
ASSESSMENT
A
small
scale
retrospective
ground
water
monitoring
study
was
completed
on
a
rangeland
site
at
a
ranch
near
Sarita,
Texas.
The
study
was
conducted
in
a
portion
of
a
540
acre
area
treated
with
Tebuthiuron
in
March
1986
by
aerial
broadcast
in
70
foot
wide
strips.
Tebuthiuron
was
applied
at
rates
between
1.5
and
1.75
lbs
a.
i./
acre
for
rangeland
brush
control.
Higher
application
up
to
2
lbs
a.
i./
acre
were
applied
in
bands
to
thick
stands
of
live
oak
and
along
fence
lines.
In
some
areas
at
the
site
overlap
of
rangeland
and
fence
line
treatments
resulted
in
total
application
of
up
to
4
lbs
a.
i./
acre.
A
total
of
16
soil
borings,
14
test
pits,
and
5
ground
water
monitoring
wells
were
performed
to
complete
site
characterization.
The
site
characterization
gives
a
high
level
of
confidence
that
this
study
was
performed
with
a
reasonable
"high
exposure"
scenario.
The
site
is
comprised
of
eolian
sands
over
fluvial
deposits.
Monitoring
wells
were
installed
to
avoid
discontinuous,
restrictive
clay
layers
that
are
found
beneath
some
portions
of
the
site.
Using
the
site
characterization
data,
a
study
protocol
was
developed
and
field
work
began
in
May
1990
and
included
the
installation
of
an
additional
5
ground
water
monitoring
wells.
A
program
of
ground
water
analysis
was
begun
in
which
seven
of
the
ten
ground
water
monitoring
wells
were
sampled
every
other
month
beginning
in
June
1990
and
ending
June
1991.
Analysis
of
soil
samples
indicated
that
Tebuthiuron
was
still
present
in
soil
at
depths
greater
than
three
feet
below
ground
surface
and
appeared
to
be
in
contact
with
shallow
ground
water
beneath
portions
of
the
study
site.
No
degradate
was
detected
in
soil
samples
above
the
limit
of
detection
of
0.01
mg/
L.
The
data
suggest
that
Tebuthiuron
is
persistent
and
mobile
in
soil
at
the
study
site.
Analysis
of
ground
water
samples
collected
beneath
the
study
site
indicate
that
Tebuthiuron
was
present
above
the
limit
of
detection
(0.001
mg/
L)
in
six
of
the
seven
wells
at
the
site
and
was
detected
above
the
limit
of
quantitation
(0.003
mg/
L)
in
three
of
the
seven
wells
with
a
maximum
concentration
of
0.023
mg/
L
four
years
after
application.
Compound
104
was
detected
above
the
limit
of
detection
in
three
wells
and
was
detected
at
concentrations
above
the
limit
of
quantitation
in
one
well
with
a
maximum
concentration
of
0.004
mg/
L
four
years
after
application.
This
data
indicate
that
Tebuthiuron
and
its
primary
degradate
are
persistent
and
mobile
in
ground
water
up
to
four
years
after
application.
NAWQA
Data
EFED
evaluated
the
occurrence
of
Tebuthiuron
in
ground
water
from
the
national
data
set.
Tebuthiuron
was
detected
in
228
ground
water
samples
out
of
a
total
of
5303
samples
(4.3%).
It
is
difficult
to
compare
analytical
results
from
ground
water
monitoring
wells
within
a
given
geographic
area.
A
significant
amount
of
ancillary
data
is
necessary
in
order
to
compare
wells
across
an
area.
Examples
of
the
data
that
is
needed
is
aquifer
type,
well
construction,
and
sampling
methodology.
Even
with
ancillary
data
it
is
difficult
to
compare
analytical
results
within
a
region
due
to
variations
in
geology,
geochemistry
of
ground
water,
and
groundwater
usage
patterns
and
history.
Because
this
information
is
not
readily
available
for
this
data
set,
EFED
has
conducted
a
general
analysis
of
the
data.
The
maximum
concentration
detected
across
all
samples
is
17.3
:
g/
L
with
a
detection
limit
of
0.010
:
g/
L,
while
the
average
concentration
among
all
reported
Tebuthiuron
data
is
0.016
:
g/
L.
Depth
to
ground
water
across
the
entire
NAWQA
data
ranged
from
near
surface
to
greater
than
600
feet
below
ground
surface
with
an
average
depth
of
33
feet
below
ground
surface.
Depth
to
ground
water
in
the
focused
NAWQA
study
units
from
Texas,
Oklahoma,
and
New
Mexico
ranged
from
2
to
177
feet
below
ground
surface
with
an
average
depth
of
17
feet
below
ground
surface.
The
depth
to
ground
water
data
suggest
that
the
peak
and
average
concentrations
are
representative
of
the
shallowest
aquifers.
SURFACE,
GROUND
AND
DRINKING
WATER
ASSESSMENT
Because
Tebuthiuron
is
not
included
among
regulated
or
unregulated
chemicals
required
as
analytes
in
testing
of
public
drinking
water
supplies,
drinking
water
monitoring
results
are
not
available.
Therefore,
drinking
water
exposure
assessments
are
supplemented
with
modeling
predictions.
Surface
water
concentrations
of
Tebuthiuron
were
modeled
using
the
PRZM/
EXAMS
(Tier
II)
programs
for
pasture/
rangeland
using
EFEDs
standard
scenario
for
alfalfa
in
Texas.
The
alfalfa
scenario
was
chosen
because
its
hydrologic
and
agronomic
practices
closely
match
those
of
pasture/
rangeland.
Groundwater
concentrations
were
modeled
using
the
SCI
GROW
program.
Input
parameters
used
Tier
II
(PRZM
version
3.12/
EXAMS
version
2.97.5)
modeling
were
selecting
using
Agency
guidance
("
Guidance
for
Chemistry
and
Management
Practice
Input
Parameters
for
Use
in
Modeling
the
Environmental
Fate
and
Transport
of
Pesticides"
dated
August
6,
2000)
and
EFED
calculated
degradation
rate
constants
from
review
of
registrant
submitted
environmental
fate
studies.
The
assessment
strategy
was
designed
to
assess
concentrations
of
the
parent
compound
alone.
Tier
II
(PRZM
EXAMS)
surface
water
modeling
for
Tebuthiuron
(parent
only)
using
the
index
reservoir
with
the
percent
cropped
area
(PCA=
0.87
for
default
PCA)
estimates
the
concentration
of
Tebuthiuron
is
not
likely
to
exceed
the
concentrations
in
Table
7.
Table
7.
PRZM
EXAMS
Predicted
Parent
Tebuthiuron
Concentrations
in
the
Index
Reservoir
Simulation
Scenarios
Concentration
(
:
g/
L)
1
in
10
year
Mean
of
Annual
Means
Crop
and
Location
Scenario
Peak
96
Hour
21
Day
60
Day
90
Day
Annual
Mean
Pasture,
Milam
Co.,
TX
Index
Reservoir
17.4
16.6
13.2
8.1
6.0
1.7
0.7
Index
Reservoir
w/
PCA
(0.87)
15.1
14.4
11.5
7.0
5.2
1.5
0.6
SCI
GROW
predicts
a
concentration
of
Tebuthiuron
in
shallow
ground
water
of
181
µg/
L.
Appendix
A
provides
a
detailed
discussion
of
the
modeling
efforts
for
PRZM/
EXAMS
and
SCIGROW
APPENDIX
A
MODELING
DISCUSSION
DRINKING
WATER
ASSESSMENT
Uncertainties,
Assumptions
and
Limitations
Input
parameters
used
in
Tier
II
(PRZM/
EXAMS)
modeling
were
selecting
using
Agency
guidance
("
Guidance
for
Chemistry
and
Management
Practice
Input
Parameters
for
Use
in
Modeling
the
Environmental
Fate
and
Transport
of"
dated
August
6,
2000)
and
EFED
calculated
degradation
rate
constants
from
review
of
registrant
submitted
environmental
fate
studies.
Tebuthiuron
is
used
primarily
on
pasture
and
rangeland
in
Texas,
Oklahoma,
and
New
Mexico,
therefore,
only
one
scenario
was
simulated
to
estimate
runoff
concentrations.
EFED
selected
a
scenario
in
Texas
for
alfalfa
representing
an
EFED
standard
scenario
developed
for
use
in
modeling
the
respective
crops.
Alfalfa
was
selected
as
the
scenario
most
closely
representing
pasture/
rangeland
(the
alfalfa
scenario
was
developed
based
on
a
pasture
setting).
These
scenarios
were
developed
to
approximately
represent
the
90
th
percentile
site
for
runoff
vulnerability
in
a
high
usage
state.
Application
timing
was
taken
from
registrant
provided
information
and
recent
labels.
The
standard
scenario
for
alfalfa
is
based
on
usage
patterns
in
Milam
County,
Texas.
The
soil
is
a
Lufkin
sandy
loam
in
Major
Land
Use
Area
(MLRA)
87.
The
Lufkin
sandy
loam
is
characterized
as
a
Hydrologic
Group
D
soil.
The
index
reservoir
represents
potential
drinking
water
exposure
from
a
specific
area
with
specific
cropping
patterns,
weather,
soils,
and
other
factors
(use
of
an
index
reservoir
for
areas
with
different
climates,
crops,
pesticides
used,
sources
of
water,
and
hydrogeology
creates
uncertainties).
If
a
community
derives
its
drinking
water
from
a
large
river,
then
the
estimated
exposure
would
likely
be
higher
than
the
actual
exposure.
Conversely,
a
community
that
derives
its
drinking
water
from
smaller
bodies
of
water
with
minimal
outflow
would
likely
get
higher
drinking
water
exposure
than
estimated
using
the
index
reservoir.
Areas
with
a
less
humid
climate
that
use
a
similar
reservoir
and
cropping
patterns
would
likely
get
less
pesticides
in
their
drinking
water
than
predicted
levels.
A
single
steady
flow
has
been
used
to
represent
the
flow
through
the
reservoir.
Discharge
from
the
reservoir
also
removes
chemical
from
it
so
this
assumption
will
underestimate
removal
from
the
reservoir
during
wet
periods
and
overestimates
removal
during
dry
periods.
This
assumption
can
both
underestimate
or
overestimate
the
concentration
in
the
pond
depending
upon
the
annual
precipitation
pattern
at
the
site.
The
index
reservoir
scenario
uses
the
characteristic
of
a
single
soil
to
represent
the
soil
in
the
basin.
In
fact,
soils
can
vary
substantially
across
even
small
areas,
and
thus,
this
variation
is
not
reflected
in
these
simulations.
The
index
reservoir
scenario
does
not
consider
tile
drainage.
Areas
that
are
prone
to
substantial
runoff
are
often
tile
drained.
This
may
underestimate
exposure,
particularly
on
a
chronic
basis.
EXAMS
is
unable
to
easily
model
spring
and
fall
turnover
which
results
in
complete
mixing
of
the
chemical
through
the
water
column
at
these
times.
Because
of
this
inability,
Shipman
City
Lake
has
been
simulated
without
stratification.
There
is
data
to
suggest
that
Shipman
City
Lake
does
indeed
stratify
in
the
deepest
parts
of
the
lake
at
least
in
some
years.
This
may
result
in
both
over
and
underestimation
of
the
concentration
in
drinking
water
depending
upon
the
time
of
the
year
and
the
depth
the
drinking
water
intake
is
drawing
from.
PRZM/
EXAMS
is
a
field
scale
model
which
treats
watersheds
as
large
fields.
It
assumes
that
the
entire
area
of
the
watershed
is
planted
with
the
crop
of
interest
(i.
e.,
100%
crop
coverage).
This
assumption
may
not
hold
for
areas
larger
than
a
few
hectares,
such
as
watersheds
containing
drinking
water
reservoirs.
Therefore,
pesticide
concentrations
(peak
and/
or
long
term
average)
were
estimated
with
PRZM/
EXAMS
(the
index
reservoir
modification
changes
the
surface
water
body
parameters
used
in
EXAMS)
and
the
model
results
from
PRZM/
EXAMS
were
adjusted
by
a
factor
that
represents
the
maximum
percent
crop
area
found
for
the
crop
or
crops
being
evaluated.
Percent
crop
areas
(PCAs)
were
derived
on
a
watershed
basis
with
GIS
tools
using
1992
Census
of
Agriculture
data
and
8
digit
Hydrologic
Unit
Code
(HUC)
coverage
for
the
coterminous
United
States.
The
maximum
PCA
derived
from
this
project
was
selected
to
represent
the
modeled
crop
or
crops.
The
PCA
assumes
the
distribution
of
the
crops
within
a
county
is
uniform
and
homogeneous
throughout
the
county
area.
Distance
between
the
treated
fields
and
the
water
body
is
not
addressed.
The
PCA
is
a
watershed
based
modification.
Implicit
in
its
application
is
the
assumption
that
currently
used
field
scale
models
reflect
basin
scale
processes
consistently
for
all
pesticides
and
uses.
In
other
words,
we
assume
that
the
large
field
simulated
by
the
coupled
PRZM
and
EXAMS
models
is
a
reasonable
approximation
of
pesticide
fate
and
transport
within
a
watershed
that
contains
a
drinking
water
reservoir.
If
the
models
fail
to
capture
pertinent
basin
scale
fate
and
transport
processes
consistently
for
all
pesticides
and
all
uses,
the
application
of
a
factor
that
reduces
the
estimated
concentrations
predicted
by
modeling
could,
in
some
instances,
result
in
inadvertently
passing
a
chemical
through
the
screen
that
may
actually
pose
a
risk.
Some
preliminary
assessments
made
in
the
development
of
the
PCA
suggest
that
PRZM/
EXAMS
may
not
be
realistically
capturing
basin
scale
processes
for
all
pesticides
or
for
all
uses.
A
preliminary
survey
of
water
assessments
which
compared
screening
model
estimates
to
readily
available
monitoring
data
suggest
uneven
model
results.
In
some
instances,
the
screening
model
estimates
are
more
than
an
order
of
magnitude
greater
than
the
highest
concentrations
reported
in
available
monitoring
data;
in
other
instances,
the
model
estimates
are
less
than
monitoring
concentrations.
Because
of
these
concerns,
the
SAP
recommended
using
the
PCA
only
for
"major"
crops
in
the
South.
For
other
crops,
development
of
PCAs
will
depend
on
the
availability
of
relevant
monitoring
data
that
could
be
used
to
evaluate
the
result
of
the
PCA
adjustment.
Table
A
1.
Input
Parameters
for
Tebuthiuron
for
PRZM
(Version
3.12)
for
Index
Reservoir
and
PCA.
Variable
Description
Variable
(Units)
Input
Value
Source
of
Info/
Reference
Application
date(
s)
(day/
mo/
yr)
APD,
APM,
IAPYR
(day/
mo/
yr)
1
times
per
year
Product
label
or
location
specific
Incorporation
depth
DEPI
(cm)
0
Product
label
Application
rate
TAPP
(kg
a.
i.
ha
1
)
4.48
Aerial
granular
Product
label
Application
efficiency
APPEFF
(decimal)
1.00
Spray
Drift
Task
Force
Data
Spray
drift
fraction:
For
aquatic
ecological
exposure
assessment,
use
0.05
for
aerial
spray;
0.01
for
ground
spray.
For
drinking
water
assessment,
use
0.16
for
aerial
0.064
for
ground
spray.
DRFT
(decimal)
0.00
Spray
Drift
Task
Force
Data
Foliar
extraction
FEXTRA
(frac./
cm
rain)
0.5
(default)
Default
or
field
data
Decay
rate
on
foliage
PLDKRT
(day
1
)
0.0
(default)
Default
or
field
data
Volatilization
rate
from
foliage
PLVKRT
(day
1
)
0.0
(default)
Default
or
field
data
Plant
uptake
factor
UPTKF
(frac.
of
evap)
0.0
(default)
Default
or
field
data
Dissolved
phase
pesticide
decay
rate
in
surface
horizon
(aerobic
soil
metabolism)
DWRATE
(surface)
(day
1
)
T1/
2
=>
1060
days
Rate
constant
=
0.00065/
day
MRID
41328001
Adsorbed
phase
pesticide
decay
rate
in
surface
horizon
(aerobic
soil
metabolism)
DSRATE
(surface)
(day
1
)
T1/
2
=>
1060
days
Rate
constant
=
0.00065/
day
MRID
41328001
Dissolved
phase
pesticide
decay
rate
in
subsequent
subsurface
horizons
(aerobic
or
anaerobic
soil
metabolism)
DWRATE
(subsurface
horizons)
(day
1
)
T1/
2
=>
1060
days
Rate
constant
=
0.00065/
day
MRID
41328001
Adsorbed
phase
pesticide
decay
rate
in
subsequent
subsurface
horizons
(aerobic
or
anaerobic
soil
metabolism)
DSRATE
(subsurface
horizons)
(day
1
)
T1/
2
=>
1060
days
Rate
constant
=
0.00065/
day
MRID
41328001
Pesticide
partition
or
distribution
coefficients
for
each
horizon
(Leaching/
Adsorption/
Desorption)
Kd
0.84
Average
Kd
MRID
40768401
Table
A
2.
Input
Parameters
for
Tebuthiuron.
chm
Files
Used
in
EXAMS
(Version
2.97.
5)
for
Index
Reservoir
and
PCA.
Variable
Description
Variable
(Units)
Input
Value
Source
of
Info/
Reference
Henry's
law
constant
HENRY
(atm
m
3
mole
1
)
2.4
x
10
10
Atm
m
3
/mol
From
registrant
or
product
chemistry
Bacterial
biolysis
in
water
column
(aerobic
aquatic
metabolism)
KBACW
(cfu/
mL)
1
hour
1
30
days
Rate
constant
=0.00096/
hr
MRID
41372501
Bacterial
biolysis
in
benthic
sediment
(anaerobic
aquatic
or
aerobic
aquatic
metabolism)
KBACS
1
(cfu/
mL)
1
hour
1
365
days
MRID
41913101
Direct
photolysis
(aqueous
photolysis)
KDP
(hour
1
)
T1/
2
=30
days
Rate
constant
=0.00096/
hr
MRID
41365101
Base
hydrolysis
KBH
(mole
1
hour
1
)
30
days
(stable)
Rate
constant
=0.00096/
hr
1994
RED
Neutral
hydrolysis
KNH
(mole
1
hour
1
)
30
days
(stable)
Rate
constant
=0.00096/
hr
1994
RED
Acid
hydrolysis
KAH
(mole
1
hour
1
)
30
days
(stable)
Rate
constant
=0.00096/
hr
1994
RED
Partition
coefficient
for
sediments
(Leaching/
Adsorption/
Desorption)
need
Kd
from
soil
closest
to
crop
scenario
KPS
(mL
g
1
or
L
kg
1
)
Kd
=
0.84
Average
Kd
MRID
40768401
Molecular
weight
MWT
(g
mole
1
)
228.3
From
registrant
or
product
chemistry
Aqueous
solubility
(Multiply
water
solubility
by
10)
SOL
(mg
L
1
)
=
0.800
2,500
ppm
@
20°
C
From
registrant
or
product
chemistry
Vapor
pressure
VAPR
(torr)
2
x
10
6
Torr
From
registrant
or
product
chemistry
Sediment
bacteria
temperature
coefficient
QTBAS
2
Standard
value
Water
bacteria
temperature
coefficient
QTBAW
2
Standard
value
Table
A
3.
PRZM
EXAMS
Predicted
Tebuthiuron
Concentrations
in
the
Index
Reservoir
Simulation
Scenarios
Concentration
(
:
g/
L)
1
in
10
year
Mean
of
Annual
Means
Crop
and
Location
Scenario
Peak
96
Hour
21
Day
60
Day
90
Day
Annual
Mean
Pasture,
Milam
Co.,
TX
Index
Reservoir
17.4
16.6
13.2
8.
1
6.0
1.
7
0.7
Index
Reservoir
w/
PCA
(0.87)
15.1
14.4
11.5
7.
0
5.2
1.
5
0.6
TX
Alfalf
08/
06/
2001
"
Texas
Claypan
Area,
Milam
County,
Texas;
MLRA
J
87"
***
Record
3:
0.71
0.36
0
25
1
1
***
Record
6
ERFLAG
4
***
Record
7:
0.43
0.109
1
172.8
4
1
600
***
Record
8
1
***
Record
9
1
0.25
100
100
1
90
88
89
0
76
***
Record
9a
d
1
26
0101
1601
0102
1602
0103
1503
1603
0104
1604
0105
1605
0106
1506
1606
0107
1607
.003
.003
.003
.004
.004
.004
.003
.001
.000
.001
.001
.000
.001
.001
.000
.000
.110
.110
.110
.110
.110
.110
.110
.110
.110
.110
.110
.110
.110
.110
.110
.110
0108
1608
0109
1609
0110
1610
0111
1611
0112
1612
.001
.000
.000
.001
.001
.002
.002
.002
.003
.003
.110
.110
.110
.110
.110
.110
.110
.110
.110
.110
***
Record
10
NCPDS,
the
number
of
cropping
periods
36
***
Record
11
300847
201047
010848
1
300848
201048
010849
1
300849
201049
010850
1
300850
201050
010851
1
300851
201051
010852
1
300852
201052
010853
1
300853
201053
010854
1
300854
201054
010855
1
300855
201055
010856
1
300856
201056
010857
1
300857
201057
010858
1
300858
201058
010859
1
300859
201059
010860
1
300860
201060
010861
1
300861
201061
010862
1
300862
201062
010863
1
300863
201063
010864
1
300864
201064
010865
1
300865
201065
010866
1
300866
201066
010867
1
300867
201067
010868
1
300868
201068
010869
1
300869
201069
010870
1
300870
201070
010871
1
300871
201071
010872
1
300872
201072
010873
1
300873
201073
010874
1
300874
201074
010875
1
300875
201075
010876
1
300876
201076
010877
1
300877
201077
010878
1
300878
201078
010879
1
300879
201079
010880
1
300880
201080
010881
1
300881
201081
010882
1
300882
201082
010883
1
***
Record
12
PTITLE
Tebuthiuron
1
applications
@
4.48
kg/
ha
***
Record
13
36
1
0
0
***
Record
15
PSTNAM
Tebuthiuron
***
Record
16
050648
0
8
2
4.48
1
0
050649
0
8
2
4.48
1
0
050650
0
8
2
4.48
1
0
050651
0
8
2
4.48
1
0
050652
0
8
2
4.48
1
0
050653
0
8
2
4.48
1
0
050654
0
8
2
4.48
1
0
050655
0
8
2
4.48
1
0
050656
0
8
2
4.48
1
0
050657
0
8
2
4.48
1
0
050658
0
8
2
4.48
1
0
050659
0
8
2
4.48
1
0
050660
0
8
2
4.48
1
0
050661
0
8
2
4.48
1
0
050662
0
8
2
4.48
1
0
050663
0
8
2
4.48
1
0
050664
0
8
2
4.48
1
0
050665
0
8
2
4.48
1
0
050666
0
8
2
4.48
1
0
050667
0
8
2
4.48
1
0
050668
0
8
2
4.48
1
0
050669
0
8
2
4.48
1
0
050670
0
8
2
4.48
1
0
050671
0
8
2
4.48
1
0
050672
0
8
2
4.48
1
0
050673
0
8
2
4.48
1
0
050674
0
8
2
4.48
1
0
050675
0
8
2
4.48
1
0
050676
0
8
2
4.48
1
0
050677
0
8
2
4.48
1
0
050678
0
8
2
4.48
1
0
050679
0
8
2
4.48
1
0
050680
0
8
2
4.48
1
0
050681
0
8
2
4.48
1
0
050682
0
8
2
4.48
1
0
050683
0
8
2
4.48
1
0
***
Record
17
0
1
0
***
Record
19
STITLE
Lufkin
Sandy
Loam;
HYDG:
D
***
Record
20
100
0
0
0
0
0
0
0
0
0
***
Record
26
0
0
0
***
Record
33
3
1
10
1.55
0.215
0
0
0
0.0006540.000654
0
0.1
0.215
0.105
1.16
0.84
2
8
1.55
0.215
0
0
0
0.0006540.000654
0
1
0.215
0.105
1.16
0.84
3
82
1.6
0.32
0
0
0
0.0006540.000654
0
2
0.32
0.2
0.29
0.84
***
Record
40
0
YEAR
10
YEAR
10
YEAR
10
1
1
1
7
YEAR
PRCP
TCUM
0
0
RUNF
TCUM
0
0
INFL
TCUM
1
1
ESLS
TCUM
0
0
1.0E3
RFLX
TCUM
0
0
1.0E5
EFLX
TCUM
0
0
1.0E5
RZFX
TCUM
0
0
1.0E5
SET
MODE
=
3
CHEM
NAME
IS
Tebuthiuron
Read
ENV
c:\
mark\
przmexam\
exam\
irtxalf.
exv
SET
MWT(*)
=
228.3
SET
SOL(*,*)
=
2500.0
SET
PRBEN
=
0.05
SET
VAPR(
1)=
0.20E
05
SET
KBACW(*,*,
1)=
0.00096
SET
KBACS(*,*,
1)=
0.0
SET
QTBAS(*,*,
1)=
2.0
SET
QTBAW(*,*,
1)=
2.0
SET
KDP(*,
1)=
0.00096
SET
KBH(*,*,
1)=
0.000
SET
KNH(*,*,
1)=
0.000
SET
KAH(*,*,
1)=
0.000
SET
KPS(*,
1)=
0.84
SET
YEAR1
=
1948
READ
PRZM
P2E
C1.
D48
RUN
READ
PRZM
P2E
C1.
D49
CONTINUE
READ
PRZM
P2E
C1.
D50
CONTINUE
READ
PRZM
P2E
C1.
D51
CONTINUE
READ
PRZM
P2E
C1.
D52
CONTINUE
READ
PRZM
P2E
C1.
D53
CONTINUE
READ
PRZM
P2E
C1.
D54
CONTINUE
READ
PRZM
P2E
C1.
D55
CONTINUE
READ
PRZM
P2E
C1.
D56
CONTINUE
READ
PRZM
P2E
C1.
D57
CONTINUE
READ
PRZM
P2E
C1.
D58
CONTINUE
READ
PRZM
P2E
C1.
D59
CONTINUE
READ
PRZM
P2E
C1.
D60
CONTINUE
READ
PRZM
P2E
C1.
D61
CONTINUE
READ
PRZM
P2E
C1.
D62
CONTINUE
READ
PRZM
P2E
C1.
D63
CONTINUE
READ
PRZM
P2E
C1.
D64
CONTINUE
READ
PRZM
P2E
C1.
D65
CONTINUE
READ
PRZM
P2E
C1.
D66
CONTINUE
READ
PRZM
P2E
C1.
D67
CONTINUE
READ
PRZM
P2E
C1.
D68
CONTINUE
READ
PRZM
P2E
C1.
D69
CONTINUE
READ
PRZM
P2E
C1.
D70
CONTINUE
READ
PRZM
P2E
C1.
D71
CONTINUE
READ
PRZM
P2E
C1.
D72
CONTINUE
READ
PRZM
P2E
C1.
D73
CONTINUE
READ
PRZM
P2E
C1.
D74
CONTINUE
READ
PRZM
P2E
C1.
D75
CONTINUE
READ
PRZM
P2E
C1.
D76
CONTINUE
READ
PRZM
P2E
C1.
D77
CONTINUE
READ
PRZM
P2E
C1.
D78
CONTINUE
READ
PRZM
P2E
C1.
D79
CONTINUE
READ
PRZM
P2E
C1.
D80
CONTINUE
READ
PRZM
P2E
C1.
D81
CONTINUE
READ
PRZM
P2E
C1.
D82
CONTINUE
READ
PRZM
P2E
C1.
D83
CONTINUE
Tebuthiuron
on
Pasture
in
Texas
WATER
COLUMN
DISSOLVED
CONCENTRATION
(PPB)
YEAR
PEAK
96
HOUR
21
DAY
60
DAY
90
DAY
YEARLY
1948
4.558
4.303
3.627
2.252
1.678
0.491
1949
1.216
1.148
0.928
0.598
0.445
0.137
1950
10.440
9.861
7.831
4.873
3.605
0.958
1951
21.420
20.230
16.060
9.896
7.466
2.015
1952
9.117
8.612
6.840
4.257
3.149
0.871
1953
1.768
1.667
1.292
0.788
0.586
0.179
1954
0.148
0.139
0.109
0.072
0.056
0.023
1955
9.022
8.536
6.810
4.244
3.140
0.854
1956
0.178
0.168
0.133
0.082
0.065
0.034
1957
9.876
9.328
7.405
4.575
3.386
0.872
1958
4.589
4.334
3.435
2.109
1.567
0.455
1959
4.282
4.044
3.158
1.989
1.485
0.430
1960
17.050
16.270
12.910
7.886
5.853
1.724
1961
5.934
5.671
4.674
2.912
2.156
0.707
1962
16.330
15.490
12.420
7.693
5.694
1.553
1963
0.679
0.642
0.511
0.314
0.233
0.095
1964
9.273
8.762
7.099
4.369
3.235
0.870
1965
1.998
1.887
1.499
0.933
0.697
0.201
1966
3.022
2.854
2.266
1.400
1.041
0.291
1967
3.743
3.509
2.710
1.747
1.370
0.391
1968
0.294
0.282
0.225
0.138
0.103
0.049
1969
9.944
9.392
7.351
4.667
3.694
1.060
1970
0.232
0.227
0.206
0.167
0.143
0.055
1971
8.399
7.933
6.245
3.891
2.909
0.808
1972
5.950
5.620
4.455
2.741
2.031
0.587
1973
3.450
3.304
2.655
1.641
1.215
0.354
1974
1.165
1.108
0.878
0.558
0.431
0.139
1975
4.268
4.034
3.206
1.986
1.470
0.438
1976
5.716
5.398
4.275
2.646
1.968
0.585
1977
0.300
0.283
0.222
0.136
0.109
0.057
1978
18.300
17.290
13.730
8.536
6.323
1.642
1979
2.098
1.967
1.660
1.234
1.057
0.346
1980
0.203
0.191
0.150
0.099
0.078
0.034
1981
33.920
32.280
25.780
15.920
11.780
3.384
1982
5.063
4.782
4.043
2.524
1.871
0.570
1983
2.171
2.050
1.633
1.031
0.765
0.224
SORTED
FOR
PLOTTING
PROB
PEAK
96
HOUR
21
DAY
60
DAY
90
DAY
YEARLY
0.027
33.920
32.280
25.780
15.920
11.780
3.384
0.054
21.420
20.230
16.060
9.896
7.466
2.015
0.081
18.300
17.290
13.730
8.536
6.323
1.724
0.108
17.050
16.270
12.910
7.886
5.853
1.642
0.135
16.330
15.490
12.420
7.693
5.694
1.553
0.162
10.440
9.861
7.831
4.873
3.694
1.060
0.189
9.944
9.392
7.405
4.667
3.605
0.958
0.216
9.876
9.328
7.351
4.575
3.386
0.872
0.243
9.273
8.762
7.099
4.369
3.235
0.871
0.270
9.117
8.612
6.840
4.257
3.149
0.870
0.297
9.022
8.536
6.810
4.244
3.140
0.854
0.324
8.399
7.933
6.245
3.891
2.909
0.808
0.351
5.950
5.671
4.674
2.912
2.156
0.707
0.378
5.934
5.620
4.455
2.741
2.031
0.587
0.405
5.716
5.398
4.275
2.646
1.968
0.585
0.432
5.063
4.782
4.043
2.524
1.871
0.570
0.459
4.589
4.334
3.627
2.252
1.678
0.491
0.486
4.558
4.303
3.435
2.109
1.567
0.455
0.514
4.282
4.044
3.206
1.989
1.485
0.438
0.541
4.268
4.034
3.158
1.986
1.470
0.430
0.568
3.743
3.509
2.710
1.747
1.370
0.391
0.595
3.450
3.304
2.655
1.641
1.215
0.354
0.622
3.022
2.854
2.266
1.400
1.057
0.346
0.649
2.171
2.050
1.660
1.234
1.041
0.291
0.676
2.098
1.967
1.633
1.031
0.765
0.224
0.703
1.998
1.887
1.499
0.933
0.697
0.201
0.730
1.768
1.667
1.292
0.788
0.586
0.179
0.757
1.216
1.148
0.928
0.598
0.445
0.139
0.784
1.165
1.108
0.878
0.558
0.431
0.137
0.811
0.679
0.642
0.511
0.314
0.233
0.095
0.838
0.300
0.283
0.225
0.167
0.143
0.057
0.865
0.294
0.282
0.222
0.138
0.109
0.055
0.892
0.232
0.227
0.206
0.136
0.103
0.049
0.919
0.203
0.191
0.150
0.099
0.078
0.034
0.946
0.178
0.168
0.133
0.082
0.065
0.034
0.973
0.148
0.139
0.109
0.072
0.056
0.023
1/
10
17.425
16.576
13.156
8.081
5.994
1.667
MEAN
OF
ANNUAL
VALUES
=
0.652
STANDARD
DEVIATION
OF
ANNUAL
VALUES
=
0.696
UPPER
90%
CONFIDENCE
LIMIT
ON
MEAN
=
0.824
RUN
No.
2
FOR
Tebuthiuron
INPUT
VALUES
APPL
(#/
AC)
APPL.
URATE
SOIL
SOIL
AEROBIC
RATE
NO.
(#/
AC/
YR)
KOC
METABOLISM
(DAYS)
4.000
1
4.000
72.0
1060.0
GROUND
WATER
SCREENING
CONCENTRATIONS
IN
PPB
181.451200
A=
1055.000
B=
77.000
C=
3.023
D=
1.886
RILP=
6.390
F=
1.657
G=
45.363
URATE=
4.000
GWSC=
181.451200
| epa | 2024-06-07T20:31:42.582761 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0146-0003/content.txt"
} |
EPA-HQ-OPP-2002-0146-0004 | Supporting & Related Material | "2002-06-25T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
February
20,
2002
SUBJECT:
Addendum
to
Drinking
Water
Assessment
for
the
Tolerance
Reassessment
(TRED)
for
Tebuthiuron
FROM:
Mark
Corbin,
Environmental
Scientist
Environmental
Risk
Branch
1
Environmental
Fate
and
Effects
Division
(7507C)
THRU:
Dana
Spatz,
Acting
Branch
Chief
Environmental
Risk
Branch
1
Environmental
Fate
and
Effects
Division
(7507C)
TO:
Paula
Deschamp
Reregistration
Branch
II
Health
Effects
Division
(7509C)
Wilhelmena
Livingston
Special
Review
Branch
Special
Review
and
Reregistration
Division
(7508C)
EFED
has
completed
an
addendum
to
the
drinking
water
assessment
for
the
reassessment
of
tolerances
for
the
herbicide
tebuthiuron
submitted
to
the
Health
Effects
Division
(HED).
This
assessment
considers
tebuthiuron
and
its
degradates
which
the
Health
Effects
Division
(HED)
has
determined
are
of
toxicological
concern.
Compound
104
was
identified
by
the
MARC
as
the
only
environmental
fate
degradate
of
tebuthiuron
of
toxicological
concern.
However,
insufficient
fate
data
was
available
for
compound
104.
Therefore,
EFED
elected
to
model
total
tebuthiuron
residues
(TTR)
using
a
cumulative
residue
approach.
The
assessment
strategy
adopted
in
this
addendum
was
designed
to
assess
concentrations
of
the
TTR
(tebuthiuron
plus
compound
104,
compound
105,
compound
106,
compound
107,
compound
108,
and
compound
109)
which
were
detected
in
the
environmental
fate
studies.
The
name
and
chemical
structure
of
the
degradates
are
attached
as
Appendix
A.
A
cumulative
residue
approach
was
employed
to
provide
conservative
estimated
concentrations
in
drinking
water
for
tebuthiuron
and
its
degradation
products.
In
this
approach,
the
fate
parameters
necessary
for
Tier
II
modeling
are
estimated
from
the
total
residue
data
in
the
environmental
fate
studies
previously
submitted.
For
tebuthiuron,
total
residue
data
was
evaluated
for
the
aerobic
soil
metabolism
(MRID
41328001)
half
life,
aqueous
photolysis
(MRID
41305101)
half
life,
aerobic
aquatic
(MRID
41372501)
half
life,
anaerobic
soil
metabolism
(MRID
41328002)
half
life,
and
hydrolysis
half
lives.
Additional
fate
data
(including
Koc,
Henry's
Law
constant,
vapor
pressure,
solubility,
and
molecular
weight)
were
estimated
for
Compound
104
using
published
software
(Estimation
Programs
Interface
(EPI),
Version
3.04,
1999)
which
estimates
fate
parameter
using
published
equations.
Compound
104
was
used
as
a
reference
degradate
because
it
was
the
degradate
detected
at
the
highest
concentration
in
the
environmental
fate
studies,
is
expected
to
be
a
highly
mobile
tebuthiuron
residue
in
soil
and
aquatic
environments
based
in
its
chemical
structure
and
the
fact
that
it
was
the
only
degradate
detected
in
a
Small
Scale
Retrospective
Monitoring
study.
More
detail
on
EPI
estimation
techniques
may
be
found
at
http://
syrres.
com/
interkow/
epi.
htm.
As
with
parent
tebuthiuron,
surface
water
concentrations
of
TTR
were
modeled
using
the
PRZM/
EXAMS
(Tier
II)
programs
for
pasture/
rangeland
using
EFEDs
standard
scenario
for
alfalfa
in
Texas.
The
alfalfa
scenario
was
chosen
because
its
hydrologic
and
agronomic
practices
are
expected
to
approximate
those
of
pasture/
rangeland.
Groundwater
concentrations
were
modeled
using
the
SCI
GROW
program.
Input
parameters
used
Tier
II
(PRZM
version
3.12/
EXAMS
version
2.97.5)
modeling
were
selecting
using
Agency
guidance
("
Guidance
for
Chemistry
and
Management
Practice
Input
Parameters
for
Use
in
Modeling
the
Environmental
Fate
and
Transport
of
Pesticides"
dated
August
6,
2000)
and
EFED
calculated
degradation
rate
constants
from
review
of
registrant
submitted
environmental
fate
studies
as
note
above.
Tier
II
(PRZM
version
3.12/
EXAMS
version
2.97.5)
surface
water
modeling
for
TTR
due
to
use
of
tebuthiuron
use
on
rangeland/
pasture
at
4
pounds
active
ingredient
per
acre
(lbs
ai/
A)
using
the
index
reservoir
and
a
PCA
of
0.87
predicts
the
1
in
10
year
annual
maximum
(acute)
concentration
of
15.52
:
g/
L.
The
1
in
10
year
annual
average
concentration
(non
cancer
chronic)
of
tebuthiuron
is
predicted
to
be
4.31
:
g/
L
.
The
36
year
annual
average
concentration
(cancer
chronic)
of
tebuthiuron
is
predicted
to
be
1.96
:
g/
L.
SCI
GROW
(version
2.1)
modeling
estimates
the
acute
and
chronic
concentration
of
TTR
in
shallow
groundwater
is
245
:
g/
L.
A
comparison
of
the
TTR
concentrations
compared
with
the
parent
only
values
previously
submitted
are
presented
in
Table
1.
A
more
detailed
modeling
discussion
is
presented
in
Appendix
B.
Table
1.
Comparison
of
PRZM
EXAMS
Predicted
Total
Tebuthiuron
Residue
(TTR)
Concentrations
with
Predicted
Parent
Tebuthiuron
Concentrations
in
the
Index
Reservoir
Simulation
Scenarios
Concentration
(
:
g/
L)
1
in
10
year
Mean
of
Annual
Means
Crop
and
Location
Scenario
Peak
96
Hour
21
Day
60
Day
90
Day
Annual
Mean
Pasture,
Milam
Co.,
TX
Total
Residues
w/
PCA
(0.87)
15.5
15.3
14.3
12.2
10.9
4.3
2.0
Parent
Only
w/
PCA
(0.87)
15.1
14.4
11.5
7.0
5.2
1.5
0.6
Appendix
B
provides
a
detailed
discussion
of
the
modeling
efforts
for
PRZM/
EXAMS,
and
SCIGROW
APPENDIX
A
DEGRADATE
NAMES
and
STRUCTURES
N
N
S
N
CH
3
CH
3
C
H
3
C
H
3
O
NH
2
Table
1.
Degradates
of
Tebuthiuron
with
maximum
applied
detected
in
each
study:
Parent
/
Degradate
Name
and
Structure
Percent
of
Applied
Dose
MRID
#
Study
Type
Reported
Values
Maximum
Day
*104:
N[
5(
1,1
dimethylethyl)
1,3,4
thiadiazol
2
yl]
methylurea
ND
N/
A
N/
A
hydrolysis
ND
N/
A
41305101
aqueous
photolysis
6.8
14
41050201
soil
photolysis
6.9
270
41328001
aerobic
soil
Nmetabolism
2.9
60
41328002
anaerobic
soil
metabolism
1.5
21
41372501
aerobic
aquatic
metabolism
ND
N/
A
41913101
anaerobic
aquatic
metabolism
ND
N/
A
40768401
batch
equilibrium
N/
A
N/
A
N/
A
laboratory
volatility
N/
A
N/
A
N/
A
field
volatility
22.9
408
43318101
terrestrial
field
dissipation
2.2
(edible)
21
40819501
bioaccumulation
in
fish
105:
N[
5(
1,1
dimethylethyl)
1,3,4
thiadiazol
2
yl]
N
methylurea
ND
N/
A
N/
A
hydrolysis
ND
N/
A
41305101
aqueous
photolysis
3.5
19
41050201
soil
photolysis
0.4
90
41328001
aerobic
soil
metabolism
0.2
60
41328002
anaerobic
soil
metabolism
0.4
28
41372501
aerobic
aquatic
metabolism
ND
N/
A
41913101
anaerobic
aquatic
metabolism
ND
N/
A
40768401
batch
equilibrium
Parent
/
Degradate
Name
and
Structure
Percent
of
Applied
Dose
MRID
#
Study
Type
Reported
Values
Maximum
Day
N
N
S
N
H
CH
3
C
H
3
C
H
3
O
NH
2
N/
A
N/
A
N/
A
laboratory
volatility
N/
A
N/
A
N/
A
field
volatility
ND
N/
A
43318101
terrestrial
field
dissipation
4.7
(edible)
21
40819501
bioaccumulation
in
fish
106:
N[
5(
1,1
dimethylethyl)
1,3,4
thiadiazol
2
yl]
urea
ND
N/
A
N/
A
hydrolysis
ND
N/
A
41305101
aqueous
photolysis
2.7
5
41050201
soil
photolysis
ND
N/
A
41328001
aerobic
soil
metabolism
ND
N/
A
41328002
anaerobic
soil
metabolism
ND
N/
A
41372501
aerobic
aquatic
metabolism
ND
N/
A
41913101
anaerobic
aquatic
metabolism
ND
N/
A
40768401
batch
equilibrium
N/
A
N/
A
N/
A
laboratory
volatility
N/
A
N/
A
N/
A
field
volatility
ND
N/
A
43318101
terrestrial
field
dissipation
ND
N/
A
40819501
bioaccumulation
in
fish
107:
5(
1,1
Dimethylethyl)
2
methylamino
1,3,4
thiadiazole
ND
N/
A
N/
A
hydrolysis
ND
N/
A
41305101
aqueous
photolysis
ND
N/
A
41050201
soil
photolysis
1.1
270
41328001
aerobic
soil
metabolism
ND
N/
A
41328002
anaerobic
soil
metabolism
Parent
/
Degradate
Name
and
Structure
Percent
of
Applied
Dose
MRID
#
Study
Type
Reported
Values
Maximum
Day
N
N
S
NH
2
CH
3
C
H
3
C
H
3
0.3
21
41372501
aerobic
aquatic
metabolism
ND
N/
A
41913101
anaerobic
aquatic
metabolism
ND
N/
A
40768401
batch
equilibrium
N/
A
N/
A
N/
A
laboratory
volatility
N/
A
N/
A
N/
A
field
volatility
ND
N/
A
43318101
terrestrial
field
dissipation
ND
N/
A
40819501
bioaccumulation
in
fish
108:
2
dimethylethyl
5
amino
1,3,4
thiadiazole
ND
N/
A
N/
A
hydrolysis
ND
N/
A
41305101
aqueous
photolysis
ND
N/
A
41050201
soil
photolysis
0.6
270
41328001
aerobic
soil
metabolism
ND
N/
A
41328002
anaerobic
soil
metabolism
0.1
7
41372501
aerobic
aquatic
metabolism
ND
N/
A
41913101
anaerobic
aquatic
metabolism
ND
N/
A
40768401
batch
equilibrium
N/
A
N/
A
N/
A
laboratory
volatility
N/
A
N/
A
N/
A
field
volatility
ND
N/
A
43318101
terrestrial
field
dissipation
ND
N/
A
40819501
bioaccumulation
in
fish
Parent
/
Degradate
Name
and
Structure
Percent
of
Applied
Dose
MRID
#
Study
Type
Reported
Values
Maximum
Day
N
N
S
N
CH
3
CH
3
C
H
3
C
H
3
O
N
H
OH
N
N
S
N
CH
3
CH
3
C
H
3
C
H
3
O
N
H
CH
3
N
N
S
N
CH
3
CH
3
C
H
3
O
N
H
CH
3
OH
*109:
N[
5(
1,1
dimethylethyl)
1,3,4
thiadiazol
2
yl]
hydroxymethyl
methylurea
ND
N/
A
N/
A
hydrolysis
ND
N/
A
41305101
aqueous
photolysis
ND
N/
A
41050201
soil
photolysis
N'ND
N/
A
41328001
aerobic
soil
Nmetabolism
0.2
60
41328002
anaerobic
soil
metabolism
0.3
7
41372501
aerobic
aquatic
metabolism
ND
N/
A
41913101
anaerobic
aquatic
metabolism
ND
N/
A
40768401
batch
equilibrium
N/
A
N/
A
N/
A
laboratory
volatility
N/
A
N/
A
N/
A
field
volatility
ND
N/
A
43318101
terrestrial
field
dissipation
40.1
(edible)
21
40819501
bioaccumulation
in
fish
Attachment
1:
Additional
structures
of
tebuthiuron
and
its
metabolites:
Tebuthiuron
(103):
[N[
5(
1,1
dimethylethyl
1,3,4
thiadiazol
2
yl]
N,
N'
dimethylurea
Matrices:
grass
forage
and
hay,
ruminant
and
milk
103
(OH):
N[
5(
2
hydroxy
1,1
dimethylethyl
1,3,4
thiadiazol
2
yl]
N,
N'
dimethylurea
Matrices:
ruminant
and
milk
N
N
S
N
CH
3
CH
3
C
H
3
O
NH
2
OH
N
N
S
N
CH
3
CH
3
C
H
3
O
N
H
OH
OH
N
N
S
N
C
CH3
H3C
CH3
H
C
O
N
CH3
H
Tebuthiuron
105
N
N
S
N
C
CH3
H3C
CH3
H
CH3
Tebuthiuron
107
104
(OH):
N[
5(
2
hydroxy
1,1
dimethylethyl
1,3,4
thiadiazol
2
yl]
N
methylurea
Matrices:
milk
A
[109
(OH)]:
N[
5(
2
hydroxy
1,1
dimethylethyl)
1,3,4
thiadiazol
2
yl]
N
hydroxymethyl
N
methylurea
Matices:
milk
105:
N[
5(
1,1
dimethylethyl)
1,3,4
thiadiazol
2
yl
N'
methylurea
Matrices:
water
107:
5(
1,1
Dimethylethyl)
2
methylamino
1,3,4
thiadi
azol
e
Matr
ices
:wat
er
and
tissu
es
cc:
SF,
RF,
List
A
files,
S.
Piper,
M.
Corbin
RDI:
FBSuhre:
/01;
MARC:
/01
7509C:
CEB:
CM
2:
Room
810F:
308
2717:
Tebuthiuron
APPENDIX
B
MODELING
DISCUSSION
DRINKING
WATER
ASSESSMENT
Uncertainties,
Assumptions
and
Limitations
Input
parameters
used
in
Tier
II
(PRZM/
EXAMS)
modeling
were
selecting
using
Agency
guidance
("
Guidance
for
Chemistry
and
Management
Practice
Input
Parameters
for
Use
in
Modeling
the
Environmental
Fate
and
Transport
of"
dated
August
6,
2000)
and
EFED
calculated
degradation
rate
constants
from
review
of
registrant
submitted
environmental
fate
studies.
Tebuthiuron
is
used
primarily
on
pasture
and
rangeland
in
Texas,
Oklahoma,
and
New
Mexico,
therefore,
only
one
scenario
was
simulated
to
estimate
runoff
concentrations.
EFED
selected
a
scenario
in
Texas
for
alfalfa
representing
an
EFED
standard
scenario
developed
for
use
in
modeling
the
respective
crops
and
is
expected
to
be
the
standard
scenario
in
the
tebuthiuron
use
with
the
highest
runoff
potential.
Alfalfa
was
selected
as
the
scenario
most
closely
representing
pasture/
rangeland
(the
alfalfa
scenario
was
developed
based
on
a
pasture
setting).
These
scenarios
were
developed
to
approximately
represent
the
90
th
percentile
site
for
runoff
vulnerability
in
a
high
usage
state.
Application
timing
was
taken
from
registrant
provided
information
and
recent
labels.
The
standard
scenario
for
alfalfa
is
based
on
usage
patterns
in
Milam
County,
Texas.
The
soil
is
a
Lufkin
sandy
loam
in
Major
Land
Use
Area
(MLRA)
87.
The
Lufkin
sandy
loam
is
characterized
as
a
Hydrologic
Group
D
soil.
Uncertainties,
Assumptions
and
Limitations
There
are
several
uncertainties
and
assumptions
in
the
assessment
of
tebuthiuron
and
its
degradates.
Primary
among
these
is
the
lack
of
environmental
fate
data
for
the
transformation
products
of
tebuthiuron.
In
order
to
address
this
uncertainty,
EFED
has
conducted
the
Tier
II
modeling
(PRZM/
EXAMS)
on
the
summed
tebuthiuron
residues
(tebuthiuron
and
its
identifiable
degradation
products
including
compound
104,
compound
105,
compound
106,
compound
107,
compound
108,
and
compound
109)
instead
of
individual
residues.
Although
the
persistence
of
the
tebuthiuron
residues
was
estimated
from
registrant
submitted
environmental
fate
data,
the
mobility
of
tebuthiuron
residues
was
estimated
using
the
degradate
compound
104
(N[
5(
1,1
dimethylethyl)
1,3,4
thiadiazol
2
yl]
N
methylurea)
as
a
reference
compound.
This
compound
was
used
to
assess
mobility
because
it
was
the
degradate
detected
at
the
highest
concentration
in
the
environmental
fate
studies,
is
expected
to
be
a
highly
mobile
tebuthiuron
residue
in
soil
and
aquatic
environments,
and
was
the
only
degradate
detected
in
a
Retrospective
Ground
Water
Study.
EFED
used
the
lowest
Kd/
Koc
value
for
tebuthiuron
as
the
Kd/
Koc
for
Compound
104.
Physical
chemistry
parameters
were
estimated
for
compound
104
(Estimation
Programs
Interface
(EPI),
Version
3.04,
1999)
and
degradation
rate
constants
were
estimated
by
performing
linear
regression
on
the
total
residues
(Microsoft
Excel
2000)
from
several
fate
studies.
Table
A
1.
Input
Parameters
for
Total
Tebuthiuron
Residues
for
PRZM
(Version
3.12)
for
Index
Reservoir
and
PCA.
Variable
Description
Variable
(Units)
Input
Value
Source
of
Info/
Reference
Application
date(
s)
(day/
mo/
yr)
APD,
APM,
IAPYR
(day/
mo/
yr)
1
times
per
year
Product
label
or
location
specific
Incorporation
depth
DEPI
(cm)
0
Product
label
Application
rate
TAPP
(kg
a.
i.
ha
1
)
4.48
Aerial
granular
Product
label
Application
efficiency
APPEFF
(decimal)
1.00
Spray
Drift
Task
Force
Data
Spray
drift
fraction:
For
aquatic
ecological
exposure
assessment,
use
0.05
for
aerial
spray;
0.01
for
ground
spray.
For
drinking
water
assessment,
use
0.16
for
aerial
0.064
for
ground
spray.
DRFT
(decimal)
0.00
Spray
Drift
Task
Force
Data
Foliar
extraction
FEXTRA
(frac./
cm
rain)
0.5
(default)
Default
or
field
data
Decay
rate
on
foliage
PLDKRT
(day
1
)
0.0
(default)
Default
or
field
data
Volatilization
rate
from
foliage
PLVKRT
(day
1
)
0.0
(default)
Default
or
field
data
Plant
uptake
factor
UPTKF
(frac.
of
evap)
0.0
(default)
Default
or
field
data
Dissolved
phase
pesticide
decay
rate
in
surface
horizon
(aerobic
soil
metabolism)
DWRATE
(surface)
(day
1
)
T1/
2
=>
2832
days
Rate
constant
=
0.000245/
day
MRID
41328001
Adsorbed
phase
pesticide
decay
rate
in
surface
horizon
(aerobic
soil
metabolism)
DSRATE
(surface)
(day
1
)
T1/
2
=>
2832
days
Rate
constant
=
0.000245/
day
MRID
41328001
Dissolved
phase
pesticide
decay
rate
in
subsequent
subsurface
horizons
(aerobic
or
anaerobic
soil
metabolism)
DWRATE
(subsurface
horizons)
(day
1
)
T1/
2
=>
2832
days
Rate
constant
=
0.000245/
day
MRID
41328001
Adsorbed
phase
pesticide
decay
rate
in
subsequent
subsurface
horizons
(aerobic
or
anaerobic
soil
metabolism)
DSRATE
(subsurface
horizons)
(day
1
)
T1/
2
=>
2832
days
Rate
constant
=
0.000245/
day
MRID
41328001
Pesticide
partition
or
distribution
coefficients
for
each
horizon
(Leaching/
Adsorption/
Desorption)
Kd
0.11
Lowest
Kd
MRID
40768401
Table
A
2.
Input
Parameters
for
Tebuthiuron.
chm
Files
Used
in
EXAMS
(Version
2.97.
5)
for
Index
Reservoir
and
PCA.
Variable
Description
Variable
(Units)
Input
Value
Source
of
Info/
Reference
Henry's
law
constant
HENRY
(atm
m
3
mole
1
)
7.58
x
10
11
Atm
m
3
/mol
EPI
Bacterial
biolysis
in
water
column
(aerobic
aquatic
metabolism)
KBACW
(cfu/
mL)
1
hour
1
683
days
Rate
constant
=0.000042/
hr
MRID
41372501
Bacterial
biolysis
in
benthic
sediment
(anaerobic
aquatic
or
aerobic
aquatic
metabolism)
KBACS
1
(cfu/
mL)
1
hour
1
0
days
(stable)
MRID
41913101
Direct
photolysis
(aqueous
photolysis)
KDP
(hour
1
)
T1/
2
=0
days
(stable)
MRID
41365101
Base
hydrolysis
KBH
(mole
1
hour
1
)
0
days
(stable)
1994
RED
Neutral
hydrolysis
KNH
(mole
1
hour
1
)
0
days
(stable)
1994
RED
Acid
hydrolysis
KAH
(mole
1
hour
1
)
0
days
(stable)
1994
RED
Partition
coefficient
for
sediments
(Leaching/
Adsorption/
Desorption)
need
Kd
from
soil
closest
to
crop
scenario
KPS
(mL
g
1
or
L
kg
1
)
Kd
=
0.11
Lowest
Kd
MRID
40768401
Molecular
weight
MWT
(g
mole
1
)
214.3
EPI
Aqueous
solubility
(Multiply
water
solubility
by
10)
SOL
(mg
L
1
)
=
0.800
2790
ppm
@
20°
C
EPI
Vapor
pressure
VAPR
(torr)
7.5
x
10
7
Torr
EPI
Sediment
bacteria
temperature
coefficient
QTBAS
2
Standard
value
Water
bacteria
temperature
coefficient
QTBAW
2
Standard
value
TX
Alfalf
08/
06/
2001
"
Texas
Claypan
Area,
Milam
County,
Texas;
MLRA
J
87"
***
Record
3:
0.71
0.36
0
25
1
1
***
Record
6
ERFLAG
4
***
Record
7:
0.43
0.109
1
172.8
4
1
600
***
Record
8
1
***
Record
9
1
0.25
100
100
1
90
88
89
0
76
***
Record
9a
d
1
26
0101
1601
0102
1602
0103
1503
1603
0104
1604
0105
1605
0106
1506
1606
0107
1607
.003
.003
.003
.004
.004
.004
.003
.001
.000
.001
.001
.000
.001
.001
.000
.000
.110
.110
.110
.110
.110
.110
.110
.110
.110
.110
.110
.110
.110
.110
.110
.110
0108
1608
0109
1609
0110
1610
0111
1611
0112
1612
.001
.000
.000
.001
.001
.002
.002
.002
.003
.003
.110
.110
.110
.110
.110
.110
.110
.110
.110
.110
***
Record
10
NCPDS,
the
number
of
cropping
periods
36
***
Record
11
300847
201047
010848
1
300848
201048
010849
1
300849
201049
010850
1
300850
201050
010851
1
300851
201051
010852
1
300852
201052
010853
1
300853
201053
010854
1
300854
201054
010855
1
300855
201055
010856
1
300856
201056
010857
1
300857
201057
010858
1
300858
201058
010859
1
300859
201059
010860
1
300860
201060
010861
1
300861
201061
010862
1
300862
201062
010863
1
300863
201063
010864
1
300864
201064
010865
1
300865
201065
010866
1
300866
201066
010867
1
300867
201067
010868
1
300868
201068
010869
1
300869
201069
010870
1
300870
201070
010871
1
300871
201071
010872
1
300872
201072
010873
1
300873
201073
010874
1
300874
201074
010875
1
300875
201075
010876
1
300876
201076
010877
1
300877
201077
010878
1
300878
201078
010879
1
300879
201079
010880
1
300880
201080
010881
1
300881
201081
010882
1
300882
201082
010883
1
***
Record
12
PTITLE
Tebuthiuron
1
applications
@
4.48
kg/
ha
***
Record
13
36
1
0
0
***
Record
15
PSTNAM
Tebuthiuron
***
Record
16
050648
0
8
2
4.48
1
0
050649
0
8
2
4.48
1
0
050650
0
8
2
4.48
1
0
050651
0
8
2
4.48
1
0
050652
0
8
2
4.48
1
0
050653
0
8
2
4.48
1
0
050654
0
8
2
4.48
1
0
050655
0
8
2
4.48
1
0
050656
0
8
2
4.48
1
0
050657
0
8
2
4.48
1
0
050658
0
8
2
4.48
1
0
050659
0
8
2
4.48
1
0
050660
0
8
2
4.48
1
0
050661
0
8
2
4.48
1
0
050662
0
8
2
4.48
1
0
050663
0
8
2
4.48
1
0
050664
0
8
2
4.48
1
0
050665
0
8
2
4.48
1
0
050666
0
8
2
4.48
1
0
050667
0
8
2
4.48
1
0
050668
0
8
2
4.48
1
0
050669
0
8
2
4.48
1
0
050670
0
8
2
4.48
1
0
050671
0
8
2
4.48
1
0
050672
0
8
2
4.48
1
0
050673
0
8
2
4.48
1
0
050674
0
8
2
4.48
1
0
050675
0
8
2
4.48
1
0
050676
0
8
2
4.48
1
0
050677
0
8
2
4.48
1
0
050678
0
8
2
4.48
1
0
050679
0
8
2
4.48
1
0
050680
0
8
2
4.48
1
0
050681
0
8
2
4.48
1
0
050682
0
8
2
4.48
1
0
050683
0
8
2
4.48
1
0
***
Record
17
0
1
0
***
Record
19
STITLE
Lufkin
Sandy
Loam;
HYDG:
D
***
Record
20
100
0
0
0
0
0
0
0
0
0
***
Record
26
0
0
0
***
Record
33
3
1
10
1.55
0.215
0
0
0
0.00022
0.00022
0
0.1
0.215
0.105
1.16
0.11
2
8
1.55
0.215
0
0
0
0.00022
0.00022
0
1
0.215
0.105
1.16
0.11
3
82
1.6
0.32
0
0
0
0.00022
0.00022
0
2
0.32
0.2
0.29
0.11
***
Record
40
0
YEAR
10
YEAR
10
YEAR
10
1
1
1
7
YEAR
PRCP
TCUM
0
0
RUNF
TCUM
0
0
INFL
TCUM
1
1
ESLS
TCUM
0
0
1.0E3
RFLX
TCUM
0
0
1.0E5
EFLX
TCUM
0
0
1.0E5
RZFX
TCUM
0
0
1.0E5
SET
MODE
=
3
CHEM
NAME
IS
Tebuthiuron
104
Read
ENV
c:\
mark\
przmexam\
exam\
irtxalf.
exv
SET
MWT(*)
=
214.3
SET
SOL(*,*)
=
2790.0
SET
PRBEN
=
0.05
SET
VAPR(
1)=
7.50E
07
SET
HENRY(
1)
=
7.58E
11
SET
KBACW(*,*,
1)=
0.000042
SET
KBACS(*,*,
1)=
0.0
SET
QTBAS(*,*,
1)=
2.0
SET
QTBAW(*,*,
1)=
2.0
SET
KDP(*,
1)=
0.0
SET
KBH(*,*,
1)=
0.000
SET
KNH(*,*,
1)=
0.000
SET
KAH(*,*,
1)=
0.000
SET
Koc(
1)=
15.69
SET
YEAR1
=
1948
READ
PRZM
P2E
C1.
D48
RUN
READ
PRZM
P2E
C1.
D49
CONTINUE
READ
PRZM
P2E
C1.
D50
CONTINUE
READ
PRZM
P2E
C1.
D51
CONTINUE
READ
PRZM
P2E
C1.
D52
CONTINUE
READ
PRZM
P2E
C1.
D53
CONTINUE
READ
PRZM
P2E
C1.
D54
CONTINUE
READ
PRZM
P2E
C1.
D55
CONTINUE
READ
PRZM
P2E
C1.
D56
CONTINUE
READ
PRZM
P2E
C1.
D57
CONTINUE
READ
PRZM
P2E
C1.
D58
CONTINUE
READ
PRZM
P2E
C1.
D59
CONTINUE
READ
PRZM
P2E
C1.
D60
CONTINUE
READ
PRZM
P2E
C1.
D61
CONTINUE
READ
PRZM
P2E
C1.
D62
CONTINUE
READ
PRZM
P2E
C1.
D63
CONTINUE
READ
PRZM
P2E
C1.
D64
CONTINUE
READ
PRZM
P2E
C1.
D65
CONTINUE
READ
PRZM
P2E
C1.
D66
CONTINUE
READ
PRZM
P2E
C1.
D67
CONTINUE
READ
PRZM
P2E
C1.
D68
CONTINUE
READ
PRZM
P2E
C1.
D69
CONTINUE
READ
PRZM
P2E
C1.
D70
CONTINUE
READ
PRZM
P2E
C1.
D71
CONTINUE
READ
PRZM
P2E
C1.
D72
CONTINUE
READ
PRZM
P2E
C1.
D73
CONTINUE
READ
PRZM
P2E
C1.
D74
CONTINUE
READ
PRZM
P2E
C1.
D75
CONTINUE
READ
PRZM
P2E
C1.
D76
CONTINUE
READ
PRZM
P2E
C1.
D77
CONTINUE
READ
PRZM
P2E
C1.
D78
CONTINUE
READ
PRZM
P2E
C1.
D79
CONTINUE
READ
PRZM
P2E
C1.
D80
CONTINUE
READ
PRZM
P2E
C1.
D81
CONTINUE
READ
PRZM
P2E
C1.
D82
CONTINUE
READ
PRZM
P2E
C1.
D83
CONTINUE
QUIT
Tebuthiuron
Total
Residues
on
Texas
Pasture
WATER
COLUMN
DISSOLVED
CONCENTRATION
(PPB)
YEAR
PEAK
96
HOUR
21
DAY
60
DAY
90
DAY
YEARLY
1948
4.843
4.762
4.514
3.926
3.511
1.338
1949
1.543
1.517
1.432
1.234
1.107
0.705
1950
10.530
10.350
9.641
8.230
7.331
2.902
1951
21.930
21.560
20.080
17.130
15.440
6.395
1952
10.370
10.200
9.497
8.111
7.227
3.798
1953
2.216
2.179
2.030
1.734
1.548
1.066
1954
0.491
0.484
0.454
0.396
0.357
0.204
1955
9.048
8.910
8.335
7.126
6.350
2.446
1956
1.610
1.586
1.486
1.289
1.160
0.578
1957
9.920
9.753
9.082
7.767
6.923
2.612
1958
5.094
5.008
4.668
3.991
3.558
1.841
1959
4.532
4.455
4.146
3.628
3.253
1.520
1960
17.620
17.320
16.200
13.840
12.340
5.088
1961
7.075
6.996
6.646
5.702
5.085
2.951
1962
16.710
16.490
15.500
13.260
11.820
4.894
1963
3.133
3.085
2.892
2.508
2.258
1.199
1964
9.535
9.374
8.756
7.494
6.681
2.599
1965
2.535
2.493
2.322
1.984
1.777
1.143
1966
3.153
3.100
2.888
2.471
2.210
0.974
1967
3.887
3.820
3.553
3.140
2.905
1.274
1968
1.029
1.013
0.950
0.823
0.742
0.414
1969
9.976
9.808
9.127
7.989
7.465
2.969
1970
2.528
2.490
2.333
2.022
1.820
0.853
1971
8.444
8.302
7.727
6.693
6.009
2.374
1972
6.418
6.310
5.879
5.030
4.486
2.192
1973
3.866
3.801
3.562
3.046
2.715
1.372
1974
1.297
1.287
1.211
1.038
0.929
0.537
1975
4.384
4.313
4.019
3.434
3.060
1.313
1976
5.983
5.882
5.528
4.736
4.233
1.850
1977
1.284
1.265
1.185
1.028
0.925
0.516
1978
18.350
18.040
16.800
14.350
12.800
4.902
1979
3.417
3.359
3.221
2.890
2.624
1.952
1980
0.888
0.875
0.821
0.713
0.642
0.342
1981
33.960
33.630
31.500
26.900
23.960
9.423
1982
6.936
6.820
6.522
5.625
5.022
3.505
1983
2.598
2.554
2.384
2.044
1.827
1.059
SORTED
FOR
PLOTTING
PROB
PEAK
96
HOUR
21
DAY
60
DAY
90
DAY
YEARLY
0.027
33.960
33.630
31.500
26.900
23.960
9.423
0.054
21.930
21.560
20.080
17.130
15.440
6.395
0.081
18.350
18.040
16.800
14.350
12.800
5.088
0.108
17.620
17.320
16.200
13.840
12.340
4.902
0.135
16.710
16.490
15.500
13.260
11.820
4.894
0.162
10.530
10.350
9.641
8.230
7.465
3.798
0.189
10.370
10.200
9.497
8.111
7.331
3.505
0.216
9.976
9.808
9.127
7.989
7.227
2.969
0.243
9.920
9.753
9.082
7.767
6.923
2.951
0.270
9.535
9.374
8.756
7.494
6.681
2.902
0.297
9.048
8.910
8.335
7.126
6.350
2.612
0.324
8.444
8.302
7.727
6.693
6.009
2.599
0.351
7.075
6.996
6.646
5.702
5.085
2.446
0.378
6.936
6.820
6.522
5.625
5.022
2.374
0.405
6.418
6.310
5.879
5.030
4.486
2.192
0.432
5.983
5.882
5.528
4.736
4.233
1.952
0.459
5.094
5.008
4.668
3.991
3.558
1.850
0.486
4.843
4.762
4.514
3.926
3.511
1.841
0.514
4.532
4.455
4.146
3.628
3.253
1.520
0.541
4.384
4.313
4.019
3.434
3.060
1.372
0.568
3.887
3.820
3.562
3.140
2.905
1.338
0.595
3.866
3.801
3.553
3.046
2.715
1.313
0.622
3.417
3.359
3.221
2.890
2.624
1.274
0.649
3.153
3.100
2.892
2.508
2.258
1.199
0.676
3.133
3.085
2.888
2.471
2.210
1.143
0.703
2.598
2.554
2.384
2.044
1.827
1.066
0.730
2.535
2.493
2.333
2.022
1.820
1.059
0.757
2.528
2.490
2.322
1.984
1.777
0.974
0.784
2.216
2.179
2.030
1.734
1.548
0.853
0.811
1.610
1.586
1.486
1.289
1.160
0.705
0.838
1.543
1.517
1.432
1.234
1.107
0.578
0.865
1.297
1.287
1.211
1.038
0.929
0.537
0.892
1.284
1.265
1.185
1.028
0.925
0.516
0.919
1.029
1.013
0.950
0.823
0.742
0.414
0.946
0.888
0.875
0.821
0.713
0.642
0.342
0.973
0.491
0.484
0.454
0.396
0.357
0.204
1/
10
17.839
17.536
16.380
13.993
12.478
4.958
MEAN
OF
ANNUAL
VALUES
=
2.253
STANDARD
DEVIATION
OF
ANNUAL
VALUES
=
1.941
UPPER
90%
CONFIDENCE
LIMIT
ON
MEAN
=
2.732
RUN
No.
1
FOR
Compound
104
INPUT
VALUES
APPL
(#/
AC)
APPL.
URATE
SOIL
SOIL
AEROBIC
RATE
NO.
(#/
AC/
YR)
KOC
METABOLISM
(DAYS)
.276
1
.276
16.0
2832.0
GROUND
WATER
SCREENING
CONCENTRATIONS
IN
PPB
245.181800
A=
1500.000
B=
20.960
C=
3.176
D=
1.321
RILP=
8.508
F=
2.949
G=
888.340
URATE=
.276
GWSC=
245.181800
| epa | 2024-06-07T20:31:42.591300 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0146-0004/content.txt"
} |
EPA-HQ-OPP-2002-0146-0005 | Supporting & Related Material | "2002-06-25T04:00:00" | null | OFFICE
OF
PREVENTION,
PESTICIDES,
AND
TOXIC
SUBSTANCES
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
TXR
No:
0050572
March
20,
2002
Memorandum
SUBJECT:
TEBUTHIURON
(PC
Code:
105501)
Toxicology
Disciplinary
Chapter
for
the
Tolerance
Reassessment
Eligibility
Decision
Document
FROM:
Robert
Fricke,
Ph.
D.
Reregistration
Branch
2
Health
Effects
Division
(7509C)
THRU:
Alan
Nielsen,
Branch
Senior
Scientist
Reregistration
Branch
2
Health
Effects
Division
(7509C)
TO:
Paula
Deschamp,
Risk
Assessor
Reregistration
Branch
2
Health
Effects
Division
(7509C)
DP
Barcode:
D277101
Submission:
S596544
Action
Requested:
Review
toxicology
studies
submitted
by
the
registrant
and
prepare
the
toxicology
chapter
to
support
Tolerance
Reassessment
Eligibility
Decision
(TRED)
for
tebuthiuron.
Attached
is
the
updated
toxicology
chapter
summarizing
the
findings
of
the
toxicology
studies.
TEBUTHIURON
PC
Code:
105501
Toxicology
Disciplinary
Chapter
for
the
Tolerance
Reassessment
Eligibility
Decision
(TRED)
Document
February
20,
2002
Prepared
by:
Robert
F.
Fricke,
Ph.
D.
Reregistration
Branch
2
Health
Effects
Division
Mail
Code
7509C
Peer
reviewed
by:
Yung
Yang,
Ph.
D.
Toxicology
Branch
Health
Effects
Division
Mail
Code
7509C
Robert
F.
Fricke,
Toxicologist
Yung
Yang,
Toxicologist
TABLE
OF
CONTENTS
1
HAZARD
CHARACTERIZATION
........................................
1
2
REQUIREMENTS
....................................................
2
3
DATA
GAPS
.........................................................
3
4
HAZARD
ASSESSMENT
...............................................
3
4.1
Acute
Toxicity
....................................................
3
4.2
Subchronic
Toxicity
...............................................
3
4.2.1
870.3100
90
Day
Oral
Toxicity
Rat
.........................
3
4.2.2
870.3150
90
Day
Oral
Toxicity
Dog
........................
4
4.2.3
870.3200
21/
28
Day
Dermal
Toxicity
Rabbit
..................
4
4.2.4
870.3250
90
Day
Dermal
Toxicity
...........................
4
4.2.5
870.4365
90
Day
Inhalation
Toxicity
.........................
5
4.3
Prenatal
Developmental
Toxicity
......................................
5
4.3.1
870.3700a
Prenatal
Developmental
Toxicity
Study
Rat
...........
5
4.3.2
870.3700b
Prenatal
Developmental
Toxicity
Study
Rabbit
.........
6
4.4
Reproductive
Toxicity
..............................................
7
4.4.1
870.3800
Two
Generation
Reproduction
and
Fertility
Effects
Rat
..
7
4.5
Chronic
Toxicity
..................................................
8
4.5.1
870.4300
Combined
Chronic
Toxicity/
Carcinogenicity
StudyCD
SD)
BR
Rats
.................................
8
4.5.2
870.4100b
Chronic
Toxicity
Dog
............................
9
4.6
Carcinogenicity
..................................................
10
4.6.1
870.4200b
Carcinogenicity
Study
Crl:
CD
1
(ICR)
BR
Mouse
.....
10
4.6.2
870.4300
Carcinogenicity
Study
CD(
SD)
BR
Rats
..............
11
4.7
Mutagenicity
....................................................
11
4.8
Neurotoxicity
...................................................
13
4.8.1
870.6100
Delayed
Neurotoxicity
Study
Hen
..................
13
4.8.2
870.6200a
Acute
Neurotoxicity
Screening
Battery
...............
14
4.8.3
870.6200b
Subchronic
Neurotoxicity
Screening
Battery
...........
14
4.8.4
870.6300
Developmental
Neurotoxicity
Study
.................
14
4.9
Metabolism
.....................................................
14
4.9.1
870.7485
Metabolism
Rat
...............................
14
4.10
Special
Studies
..................................................
14
5
TOXICITY
ENDPOINT
SELECTION
....................................
14
5.1
Dermal
Absorption
...............................................
15
5.2
Classification
of
Carcinogenic
Potential
................................
15
5.2.1
Conclusions
and
Classification
of
Carcinogenic
Potential
...........
15
5.2.2
Quantification
of
Carcinogenic
Potential
........................
15
6
FQPA
CONSIDERATIONS
............................................
15
6.1
Special
Sensitivity
to
Infants
and
Children
..............................
15
6.2
Recommendation
for
a
Developmental
Neurotoxicity
Study
................
15
7
OTHER
ISSUES
.....................................................
15
8
REFERENCES
......................................................
15
9
APPENDICES
.......................................................
19
9.1
Toxicity
Profile
Summary
Tables
.....................................
19
9.1.1
Acute
Toxicity
Table
.......................................
19
9.1.2
Subchronic,
Chronic,
and
Other
Toxicity
Table
...................
19
9.2
Summary
of
Toxicological
Dose
and
Endpoints
for
Tebuthiuron
for
Use
in
Human
Risk
Assessment
.................................................
22
Tebuthiuron
(105501)
RED
Toxicology
Chapter
1
1
HAZARD
CHARACTERIZATION
The
toxicological
database
for
tebuthiuron
is
not
considered
adequate
for
hazard
characterization,
however
the
database
will
support
the
Tolerance
Reassessment
Eligibility
Decision
(TRED)
for
the
current
registered
uses.
Hazard
characterization
was
not
possible
because
of
datagaps
which
include
a
developmental
toxicity
study
in
rabbit,
a
chronic
feeding/
carcinogenicity
study
in
the
rat
and
oncogenicity
study
in
the
mouse;
all
of
these
studies
were
found
to
be
unacceptable.
The
requirement
for
a
developmental
neurotoxicity
study
is
being
held
in
reserve,
pending
submission
of
the
rabbit
developmental
toxicity
study.
Additionally,
the
Health
Effects
Division's
Hazard
Identification
Assessment
Review
Committee
(HIARC)
determined
that
a
28
day
inhalation
is
required
to
provide
better
hazard
characterization.
The
acute
toxicity
studies
indicate
that
tebuthiuron,
technical,
is
more
toxic
for
oral
(Toxicity
Category
II)
exposure
than
for
either
dermal
(Toxicity
Category
IV)
or
inhalation
(Toxicity
Category
III).
Tebuthiuron
is
not
an
eye
or
skin
irritant
and
not
a
skin
sensitizer.
In
the
21
day
dermal
toxicity
study
in
rabbits,
no
dermal
or
systemic
toxicity
was
observed
at
1000
mg/
kg/
day
(limit
dose).
Although
the
most
consistent
toxicological
effect
was
decreased
body
weight,
histopathological
changes
in
the
pancreas
were
observed
in
both
the
subchronic
and
chronic
toxicity
studies
in
the
rat.
Pancreatic
acinar
cells
of
both
sexes
showed
vacuolation,
which
was
described
as
generally
slight
or
affecting
only
a
few
cells;
males
also
had
increased
relative
spleen
and
prostate
gland
weights.
In
a
rat
developmental
study,
however,
pancreatic
tissue
appeared
normal.
Subchronic
and
chronic
toxicity
studies
were
available
for
the
dog.
In
a
subchronic
study,
anorexia,
with
resulting
weight
loss,
and
clinical
chemistry
effects
(increased
blood
urea
nitrogen
and
alkaline
phosphatase)
were
observed
at
50
mg/
kg/
day.
In
a
chronic
(1
year)
study
clinical
signs
of
toxicity
(emesis
anorexia,
and
diarrhea
),
decreased
body
weight,
increased
ALT
and
ALP
(males
only),
increased
absolute
and
relative
liver
weights,
and
increased
relative
kidney
(females
only)
thyroid
(males
only)
weights.
At
the
doses
tested,
neither
the
rat
nor
mouse
showed
any
treatment
related
increase
in
the
incidence
of
neoplasms.
However,
the
HIARC
(TXR
No.
0050450,
dated
February
5,
2002)
concluded
that
the
dose
levels
were
too
low
to
assess
the
carcinogenic
potential
of
tebuthiuron.
Tebuthiuron
was
not
mutagenic
in
bacteria
or
in
cultured
mammalian
cells.
There
was
also
no
indication
of
a
clastogenic
effect
up
to
toxic
doses
in
vivo.
Results
from
the
rat
developmental
and
reproductive
toxicity
studies
indicated
that
there
was
no
evidence
(qualitative
or
quantitative)
for
increased
susceptibility
following
in
utero
and/
or
pre
post
natal
exposure.
The
rabbit
developmental
toxicity
study
was
found
to
be
unacceptable;
susceptibility
can
not
be
evaluated
in
rabbits.
In
a
rat
metabolism
study
with
14
C
tebuthiuron,
absorption
was
complete;
excretion
was
rapid
both
sexes,
but
was
delayed
during
the
first
12
hours
post
dose,
indicating
saturation
of
Tebuthiuron
(105501)
RED
Toxicology
Chapter
2
biotransformation
or
excretion.
At
termination,
no
significant
amounts
of
residual
radioactivity
in
any
tissue
examined,
but
the
skin
showed
the
highest
amounts
relative
to
other
tissues.
Six
metabolites
of
tebuthiuron
were
identified.
The
major
urinary
metabolite
was
identified
as
hydroxylated
tebuthiuron
metabolites.
2
REQUIREMENTS
The
requirements
(CFR
§158.340,
revised
as
of
July
1,
1999)
for
Food
and
Non
Food
Use
for
tebuthiuron,
technical,
are
summarized
in
Table
1.
Use
of
the
new
guideline
numbers
does
not
imply
that
the
new
(1998)
guideline
protocols
were
used.
Study
Required
Satisfied
870.1100
Acute
Oral
Toxicity
.......................
870.1200
Acute
Dermal
Toxicity
.....................
870.1300
Acute
Inhalation
Toxicity
...................
870.2400
Primary
Eye
Irritation
.....................
870.2500
Primary
Dermal
Irritation
...................
870.2600
Dermal
Sensitization
......................
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
870.3100
Oral
Subchronic
(Rodent)
...................
870.3150
Oral
Subchronic
(Non
Rodent)
...............
870.3200
21
Day
Dermal
...........................
870.3250
90
Day
Dermal
...........................
870.3465
28
Day
inhalation
870.3465
90
Day
Inhalation
........................
Yes
Yes
Yes
No
Yes
No
Yes
Yes
Yes
No
a
870.3700a
Developmental
Toxicity
(Rodent)
.............
870.3700b
Developmental
Toxicity(
Non
rodent)
.........
870.3800
Reproduction
............................
Yes
Yes
Yes
Yes
No
a
Yes
870.4100a
Chronic
Toxicity
(Rodent)
...................
870.4100b
Chronic
Toxicity
(Non
rodent)
................
870.4200a
Oncogenicity
(Rat)
.........................
870.4200b
Oncogenicity
(Mouse)
......................
870.4300
Chronic/
Oncogenicity
......................
Yes
Yes
Yes
Yes
Yes
No
a
Yes
No
a
No
a
No
a
870.5100
Mutagenicity—
Gene
Mutation
bacterial
.......
870.5300
Mutagenicity—
Gene
Mutation
mammalian
.....
870.5375
Mutagenicity–
in
vitro
cytogenicity
870.5385
Mutagenicity—
Mammalian
bone
marrow
chromosomal
aberration
test
.................
870.5550
Mutagenicity—
UDS
in
Mammalian
cells
in
vitro
870.5900
In
vitro
sister
chromatid
exchange
assay
........
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
Yes
Yes
870.6100a
Acute
Delayed
Neurotox.
(Hen)
...............
870.6100b
90
Day
Neurotoxicity
(Hen)
..................
870.6200a
Acute
Neurotox.
Screening
Battery
(Rat)
........
870.6200b
90
Day
Neuro.
Screening
Battery
(Rat)
.........
870.6300
Developmental
Neurotoxicity
.................
No
No
No
No
Yes
b
No
a
870.7485
General
Metabolism
........................
870.7600
Dermal
Penetration
........................
Yes
No
Yes
Yes
a
The
HIARC
determined
that
these
studies
must
be
repeated
b
The
HIARC
determined
that
this
study
is
held
in
reserve
pending
submission
of
a
rabbit
developmental
toxicity
study
Tebuthiuron
(105501)
RED
Toxicology
Chapter
3
3
DATA
GAPS
28
day
inhalation
study
in
the
rat
(870.3465)
Developmental
toxicity
study
in
the
rabbit
(870.3700b)
Chronic
feeding/
oncogenicity
study
in
the
rat
(870.4300)
Oncogenicity
study
in
the
mouse
(870.4200)
Developmental
neurotoxicity
study
(870.6300)
(held
in
reserve)
4
HAZARD
ASSESSMENT
4.1
Acute
Toxicity
Adequacy
of
data
base
for
acute
toxicity:
The
database
for
acute
toxicity
is
considered
adequate.
The
acute
toxicity
studies
indicate
that
tebuthiuron,
technical,
is
more
toxic
for
oral
(Toxicity
Category
II)
exposure
than
for
either
dermal
(Toxicity
Category
IV)
or
inhalation
(Toxicity
Category
III).
The
primary
eye
and
skin
irritation
studies
were
both
Toxicity
Category
IV;
no
dermal
sensitization
occurred
with
tebuthiuron
in
guinea
pigs.
Acute
Toxicity
of
Tebuthiuron,
Technical
Guideline
No.
Study
Type
MRID
No.
Results
Toxicity
Category
870.1100
Acute
Oral
(Rat)
40583901
LD50
=477.5
mg/
kg
(%%)
387.5
mg/
kg
(&&)
II
870.1200
Acute
Dermal
(Rabbit)
40583902
LD50
=>
5000
mg/
kg
(%%and
&&)
IV
870.1300
Acute
Inhalation
(Rat)
00155730
LC50
=
3.696
mg/
L
III
870.2400
Primary
Eye
Irritation
40583903
Slight
irritation
IV
870.2500
Primary
Skin
Irritation
40583902
Non
irritating
IV
870.2600
Dermal
Sensitization
40583904
Non
sensitizer
4.2
Subchronic
Toxicity
Adequacy
of
data
base
for
subchronic
toxicity:
With
the
exception
of
the
28
day
inhalation
study,
the
database
for
subchronic
toxicity
is
considered
adequate.
Subchronic
studies
in
both
the
rat
and
dog,
as
well
as
a
28
dy
dermal
toxicity
study,
were
considered
to
be
acceptable.
4.2.1
870.3100
90
Day
Oral
Toxicity
Rat
Executive
Summary:
In
a
subchronic
toxicity
study
(MRID
00020662),
Harlan
SpragueDawley
rats
(10/
sex/
dose)
were
fed
diets
containing
tebuthiuron
(purity
not
given)
at
0,
400,
1000
or
2500
ppm
(0,
20,
50
or
125
mg/
kg/
day)
for
three
months.
High
dose
males
and
females
showed
decreased
body
weights,
increased
relative
liver,
kidney,
gonad
Tebuthiuron
(105501)
RED
Toxicology
Chapter
4
weights;
males
also
had
increased
relative
weights
for
spleen,
prostate
gland
and
moderate
vacuolization
of
the
pancreatic
acinar
cells.
The
LOAEL
was
established
at
125
mg/
kg/
day,
based
on
increased
relative
organ
weights
and
increased
incidence
of
vacuolization
of
the
pancreatic
acinar
cells;
the
NOAEL
was
established
at
50
mg/
kg/
day.
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
requirements
for
a
subchronic
toxicity
study
[870.3100
(§
82
1a)]
in
rats.
4.2.2
870.3150
90
Day
Oral
Toxicity
Dog
Executive
Summary:
In
a
subchronic
toxicity
study
(MRID
00020663),
beagle
dogs
(2/
sex/
dose)
were
dosed
(capsule)
with
tebuthiuron
(purity
not
given)
at
0,
12.5,
25
or
50
mg/
kg/
day
for
90
days.
Clinical
signs
were
limited
to
high
dose
dogs,
which
had
anorexia;
all
animals
survived
to
terminal
sacrifice.
High
dose
females
had
body
weight
losses
of
5%.
Transient
increases
(up
to
4
fold)
in
alkaline
phosphatase
activity
were
observed
in
high
dose
animals;
other
clinical
chemistry
parameters
were
unaffected
by
treatment.
Relative
liver
weights
were
slightly
increased
in
one
male
and
female
in
the
high
dose
group,
however,
gross
and
histopathological
observations
did
not
show
any
treatmentrelated
effects
in
these
animals.
The
LOAEL
was
established
at
50
mg/
kg/
day,
based
on
decreased
body
weight
and
increased
alkaline
phosphatase
activity;
the
NOAEL
was
established
at
25
mg/
kg/
day.
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
requirements
for
a
subchronic
toxicity
study
[870.3150
(§
82
1b)]
in
dogs.
4.2.3
870.3200
21/
28
Day
Dermal
Toxicity
Rabbit
Executive
Summary:
In
a
dermal
toxicity
study
(MRID
00149733,
00160796)
New
Zealand
White
rabbits
were
treated
for
21
days
with
tebuthiuron
(purity
not
given)
at
0
or
1000
(limit
dose)
mg/
kg/
day.
No
treatment
related
toxicity
was
observed.
The
LOAEL
was
not
established;
the
NOAEL
was
established
at
1000
mg/
kg/
day
(limit
dose)
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
requirements
for
a
21
day
dermal
toxicity
study
[870.3200
(§
82
2)]
in
rabbits.
4.2.4
870.3250
90
Day
Dermal
Toxicity
No
study
available,
not
required
4.2.5
870.4365
90
Day
Inhalation
Toxicity
Tebuthiuron
(105501)
RED
Toxicology
Chapter
5
No
study
available.
A
28
day
inhalation
study
has
been
identified
as
a
data
gap
by
the
HIARC.
4.3
Prenatal
Developmental
Toxicity
Adequacy
of
data
base
for
Prenatal
Developmental
Toxicity:
The
data
base
for
prenatal
developmental
toxicity
is
not
complete.
The
developmental
toxicity
study
in
the
rabbit
was
found
to
be
unacceptable;
the
requirement
for
a
developmental
neurotoxicity
study
is
being
held
in
reserve
pending
submission
of
this
study.
In
the
rat
developmental
toxicity
study,
no
qualitative/
quantitative
evidence
of
increased
susceptibility
was
observed.
4.3.1
870.3700a
Prenatal
Developmental
Toxicity
Study
Rat
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
00020803,
40485801),
25
presumed
pregnant
Harlan
rats
per
group
were
administered
tebuthiuron
(purity
not
given;
Lot
No.
1093
316A
259)
at
dietary
concentrations
of
0,
600,
1200,
or
1800
ppm
(0,
37,
72,
or
110
mg/
kg/
day,
respectively)
on
gestation
days
(GD)
6
15,
inclusive.
On
GD
20,
dams
were
sacrificed
and
subjected
to
gross
necropsy;
pancreatic
tissue
was
saved
from
10
females/
group
for
histopathological
examination.
Fetal
sex,
weight,
and
viability
were
determined
and
each
fetus
was
examined
for
external
abnormalities.
Approximately
onethird
of
all
fetuses
were
fixed
in
Bouin's
solution
for
subsequent
visceral
examination
and
the
remainder
were
cleared
for
skeletal
examination.
All
dams
survived
to
terminal
sacrifice.
No
treatment
related
clinical
signs
of
toxicity
were
observed
in
any
group.
Body
weights,
body
weight
gains,
and
food
consumption
by
the
low
and
mid
dose
groups
were
similar
to
the
controls
throughout
the
study.
No
treatment
related
lesions
were
observed
in
any
dam
at
necropsy.
Pancreatic
tissue,
as
evaluated
by
both
gross
and
microscopic
examination,
appeared
normal.
For
the
high
dose
group,
absolute
body
weights
were
slightly
reduced
on
GD
16
to
93%
of
the
control
level
due
to
reduced
body
weight
gains
during
the
entire
treatment
interval.
Body
weight
gains
by
the
high
dose
dams
were
21%
of
the
control
level
during
GD
6
10
and
57%
of
the
control
level
during
GD
11
15.
During
the
treatment
interval,
food
consumption
by
the
high
dose
group
was
71%
of
the
control
amount
for
GD
6
10
and
95%
of
the
control
amount
for
GD
11
15.
Compensatory
weight
gain
and
food
consumption
was
observed
in
the
high
dose
group
during
the
post
treatment
interval.
The
maternal
toxicity
LOAEL
is
1800
ppm
(110
mg/
kg/
day)
based
on
decreased
body
weight
gains
and
food
consumption.
The
maternal
toxicity
NOAEL
is
1200
ppm
(72
mg/
kg/
day).
No
differences
were
observed
between
the
treated
and
control
groups
for
pregnancy
rate,
number
of
corpora
lutea/
dam,
number
of
implantation
sites/
dam,
pre
or
post
implantation
losses,
number
of
fetuses/
litter,
fetal
body
weights,
or
fetal
sex
ratios.
No
dead
fetuses
were
observed.
Tebuthiuron
(105501)
RED
Toxicology
Chapter
6
The
total
number
of
fetuses(
litters)
available
for
examination
for
malformations/
variations
in
the
control,
low,
mid,
and
high
dose
groups
was
259(
23),
263(
21),
300(
23),
and
258(
21),
respectively.
No
treatment
related
abnormalities
were
found
in
any
fetus.
In
the
control,
low,
mid,
and
high
dose
groups,
the
total
number
of
fetuses(
litters)
with
external,
visceral,
or
skeletal
malformations/
variations
was
3(
2),
4(
4),
11(
7),
and
4(
3),
respectively.
Hydronephrosis
was
a
common
finding
in
fetuses
from
control
and
treated
groups.
The
developmental
toxicity
NOAEL
is
$
$1800
ppm
(110
mg/
kg/
day)
and
the
developmental
toxicity
LOAEL
was
not
identified.
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
requirements
for
a
developmental
toxicity
study
[870.3700
(§
83
3a)]
in
rats.
4.3.2
870.3700b
Prenatal
Developmental
Toxicity
Study
Rabbit
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
00020644),
15
presumed
pregnant
Dutch
belted
rabbits
per
group
were
administered
tebuthiuron
(96.5%
a.
i.;
Lot
No.:
B30
23
149)
by
gavage
at
doses
of
0,
10,
or
25
mg/
kg/
day
on
gestation
days
(GD)
6
18,
inclusive.
Details
of
the
purity
and
composition
and
of
the
insemination
procedure
were
given
in
MRID
41122401.
On
GD
28,
all
surviving
does
were
sacrificed
and
examined
grossly.
Litters
were
weighed
and
each
fetus
examined
for
viability,
sex,
and
external
malformations/
variations.
The
fetuses
were
killed,
examined
viscerally
by
fresh
dissection
(including
the
brain),
and
the
carcasses
processed
for
skeletal
examination.
Doses
for
the
study
were
selected
on
the
basis
of
a
preliminary
range
finding
study
(MRID
40776301).
In
this
study,
mated
rabbits
(4/
group)
were
administered
5,
10,
20,
25,
50,
or
100
mg/
kg/
day
on
GD
6
18.
Three
animals
in
the
100
mg/
kg/
day
group
died
or
were
killed
moribund
on
GD
8
10.
Overall
body
weight
changes
for
the
treated
groups
were
140,
5,
37,
72,
103,
and
480
g,
respectively.
From
the
range
finding
study,
the
percentage
of
resorptions
in
the
25,
50,
and
100
mg/
kg/
day
groups
was
68.8,
66.7,
and
100%..
In
the
main
study,
premature
deaths
of
several
animals
were
considered
incidental
to
treatment.
No
clinical
signs
of
toxicity
were
observed
in
any
animal.
No
effects
on
body
weights,
body
weight
changes,
or
food
consumption
were
noted
for
the
treated
groups
as
compared
with
the
controls.
No
treatment
related
lesions
were
found
at
gross
necropsy.
The
maternal
toxicity
NOAEL
was
established
at
25
mg/
kg/
day;
the
LOAEL
for
maternal
toxicity
was
not
established.
No
differences
between
the
treated
and
control
groups
were
noted
for
pregnancy
rate
or
numbers
of
corpora
lutea,
implantations,
fetuses/
litter,
or
resorptions.
Although
the
mean
fetal
body
weights
in
the
high
dose
group
were
significantly
lower
than
the
control
value,
the
decreases
were
attributed
to
increased
liter
size.
Tebuthiuron
(105501)
RED
Toxicology
Chapter
7
The
total
number
of
fetuses(
litters)
examined
in
the
control,
low,
and
high
dose
groups
was
48(
11),
58(
11),
and
68(
12),
respectively.
No
treatment
related
external,
visceral,
or
skeletal
malformations/
variations
were
observed
in
this
study.
The
developmental
toxicity
NOAEL
is
established
at
25
mg/
kg/
day;
the
LOAEL
was
not
established.
This
study
is
classified
as
Unacceptable/
Guideline
and
does
not
satisfy
the
guideline
requirements
for
a
developmental
toxicity
study
[870.3700
(§
83
3b)]
in
rabbits.
4.4
Reproductive
Toxicity
Adequacy
of
data
base
for
Reproductive
Toxicity:
The
data
base
for
reproductive
toxicity
is
considered
complete
and
no
additional
studies
are
required
at
this
time.
4.4.1
870.3800
Two
Generation
Reproduction
and
Fertility
Effects
Rat
Executive
Summary:
In
a
two
generation
reproduction
study
(MRID
00090108),
tebuthiuron
(Lot
No.
00880
1L
1,
X
35920,
98.0%
a.
i.)
was
fed
to
groups
of
25
male
and
25
female
Wistar
rats
per
dose
at
dietary
concentrations
of
0,
100,
200,
and
400
ppm.
The
dietary
levels
corresponded
to
doses
of
6
7,
13
14,
and
26
28
mg/
kg/
day,
respectively,
for
F0
and
F1
males
and
7
8,
14
15,
and
30
31
mg/
kg/
day,
respectively,
for
F0
and
F1
females
averaged
over
the
premating
period
only.
Adult
rats
of
both
generation
were
fed
the
treated
or
control
diets
during
the
premating
period
(98
days
for
F0
and
124
days
for
F1
rats)
and
during
mating,
gestation,
and
lactation
of
two
litters
per
generation.
Pups
from
the
F1a
litters
were
selected
to
parent
the
F2
generation.
No
treatment
related
deaths,
clinical
signs
of
toxicity,
gross
lesions,
or
microscopic
lesions
were
observed
in
adult
rats
of
either
generation.
No
treatment
related
effects
were
observed
on
body
weight,
body
weight
gain,
food
consumption,
or
food
efficiency
in
F0
male
rats,
F1
male
rats,
or
F0
female
rats
fed
any
dose
at
any
time
during
the
study
including
the
premating,
mating,
gestation,
and
lactation
periods.
F1
females
in
the
200
and
400
ppm
groups
had
mean
weekly
body
weights
7
9%
(not
biologically
significant)
and
8
13%
(p<
0.01
or
<0.05),
respectively,
less
than
the
control
group
throughout
the
premating
period
starting
with
day
21
for
the
200
ppm
group
and
day
7
for
the
400
ppm
group.
Weight
gain
over
the
entire
premating
period
was
7%
(N.
S.)
less
than
controls
for
200
ppm
group
F1
females
and
14%
(p<
0.05)
less
for
the
400
ppm
group.
Cumulative
food
consumption
was
not
significantly
affected,
but
food
efficiency
was
reduced
by
13%
(p<
0.01)
for
400
ppm
group
F1
females.
The
decreased
body
weights
and
weight
gain
did
not
extend
into
the
gestation
or
lactation
period
for
F2a
litters.
The
parental
systemic
LOAEL
was
established
at
400
ppm
(30
mg/
kg/
day)
for
female
rats
based
on
deceases
in
body
weight
and
weight
gain;
NOAEL
was
established
at
200
ppm
(14
mg/
kg/
day).
Parental
effect
levels
were
not
established
for
adult
male
rats
in
this
study.
Tebuthiuron
(105501)
RED
Toxicology
Chapter
8
No
effects
were
observed
on
reproductive
parameters
as
measured
by
sperm
morphology,
fertility
index
for
females,
and
the
number
of
litters
produced.
A
reproductive
LOAEL
was
not
established;
the
NOAEL
was
established
at
400
ppm
(30
mg/
kg/
day).
The
F1a
,
F1b
,
F2a
,
or
F2b
offspring/
litters
were
not
affected
by
treatment
with
tebuthiuron
in
the
diet.
The
mean
litter
size
at
birth,
litter
size
throughout
lactation,
survival
indices
(live
birth,
viability,
and
lactation),
and
pup
weights
and
pup
weight
gain
throughout
lactation
were
not
statistically
different
between
treated
and
control
groups.
Dosing
was
considered
to
be
barely
adequate
for
assessing
reproductive
and
offspring
toxicity.
The
offspring
LOAEL
was
not
established;
the
NOAEL
was
established
at
400
ppm
(30
mg/
kg/
day).
This
study
is
classified
Acceptable/
Guideline
and
satisfies
the
guideline
requirement
for
a
two
generation
reproductive
study
(OPPTS
870.3800,
§83
4)
in
the
rat.
4.5
Chronic
Toxicity
Adequacy
of
data
base
for
chronic
toxicity:
The
data
base
for
chronic
toxicity
is
not
complete;
datagaps
include
a
chronic
feeding/
carcinogenicity
study
in
the
rat.
It
should
be
noted
that
initial
review
of
the
carcinogenicity
studies
in
the
rat
and
mouse
by
the
RfD
Committee
on
August
28,
1992
did
not
consider
the
doses
to
be
adequate
based
on
the
absence
of
systemic
effects.
On
February
25,
1993,
however,
the
RfD
Committee
(Second
RfD/
Peer
review
report
of
Tebuthiuron,
memo
dated
March
1,
1993)
reconvened
and
found
the
rat
carcinogenicity
study
to
be
acceptable;
the
committee
felt
that
the
doses
were
considered
adequate,
or
at
least
approaching
an
adequate
dose,
for
carcinogenicity
testing
in
rats
based
on
body
weight
gain
decrease.
Even
though
the
Committee
found
the
mouse
carcinogenicity
study
to
be
unacceptable
(inadequate
dose
levels),
they
concluded
that
treatment
did
not
seem
to
alter
the
tumor
profile
for
this
strain
of
mouse
and
indicated
that
there
would
be
no
need
for
another
study.
4.5.1
870.4300
Combined
Chronic
Toxicity/
Carcinogenicity
Study
CD(
SD)
BR
Rats
Executive
Summary:
In
a
chronic
toxicity/
carcinogenicity
study
(MRID
00020714),
tebuthiuron
(>
97%
a.
i.,
lot
number,
6SG43
and
B30
23
149)
was
administered
to
male
and
female
Wistar
rats
(40/
group/
sex)
at
dietary
concentrations
of
400,
800,
or
1600
ppm
(20,
40,
and
80
mg/
kg/
day,
based
on
the
default
food
factor
of
0.05).
Two
control
groups
of
60
male
and
60
female
Wistar
rats
administered
untreated
basal
diet.
No
interim
sacrifice
was
conducted
for
this
study.
Two
replicate
studies
were
carried
out.
No
treatment
related
effects
were
reported
for
clinical
signs,
mortality,
or
clinical
pathology
in
male
or
female
rats
receiving
any
dose
of
the
test
material.
The
mortality
rates
for
all
groups
was
high.
During
the
first
year
of
treatment,
10
19%
of
males
died
Tebuthiuron
(105501)
RED
Toxicology
Chapter
9
while
at
the
end
on
the
study,
only
26%
of
all
rats
remained
alive.
Pneumonia
affected
the
majority
of
animals
in
all
groups
at
various
times
during
the
study;
antibiotic
treatment
was
required
during
one
episode.
Absolute
body
weights
presented
graphically
indicated
that
high
dose
males
and
females
weighed
less
than
controls
throughout
most
of
the
study.
The
magnitude
of
the
reduction
in
absolute
body
weight
could
not
be
determined
for
assessment
of
statistical
or
toxicologic
significance.
A
15%
reductions
in
body
weight
in
high
dose
females
was
observed
at
study
termination.
Food
consumption
was
measured
but
not
reported.
Relative
kidney
weights
were
depressed
in
high
dose
male
rats,
but
no
histopathological
correlates
were
observed.
Each
animal
was
necropsied,
but
gross
findings
were
not
tabulated.
Vacuolization
of
pancreatic
acinar
cells
(generally
slight
or
affecting
only
a
few
cells)
was
observed
in
11
males
and
13
females
receiving
the
high
dose
and
in
none
of
the
controls
of
either
sex.
Only
selected
histopathological
data
were
presented
in
the
summary
tables
of
the
study
report;
therefore,
a
complete
assessment
of
histopathological
findings
could
not
be
conducted.
No
treatment
related
neoplasms
were
reported;
common
neoplasms
included
pituitary
adenomas
and
mammary
fibroadenomas
in
female
rats.
The
microscopic
findings
in
the
pancreatic
acinar
cells
were
generally
slight,
affected
only
a
few
cells,
and
caused
no
physiological
effect
on
glucose
levels.
Based
on
the
results
of
this
study
(decreased
terminal
body
weight
in
females),
the
LOAEL
for
systemic
toxicity
was
established
at
80
mg/
kg/
day;
a
LOAEL
was
not
established
im
males.
The
NOAEL
was
established
at
40
mg/
kg/
day
in
females
at
80
mg/
k/
day
in
females.
The
HIARC
(TXR
No.
0050450,
dated
February
5,
2002)
determined
that
doses
used
in
this
study
were
not
considered
to
be
adequate
for
the
evaluation
of
the
carcinogenic
potential
of
tebuthiuron.
This
chronic
toxicity/
carcinogenicity
study
in
the
rat
is
Unacceptable/
Guideline
and
does
not
satisfy
the
guideline
requirement
for
a
chronic
toxicity/
carcinogenicity
oral
study
[OPPTS
870.4300
(§
83
5)]
in
the
rat.
4.5.2
870.4100b
Chronic
Toxicity
Dog
Executive
Summary:
In
a
one
year
chronic
toxicity
study,
tebuthiuron
(98.9%
a.
i.,
Batch
No.
X
35920)
was
administered
daily
by
capsule
to
groups
of
4
male
and
4
female
beagle
dogs
at
doses
of
0,
12.5,
25.0,
or
50.0
mg/
kg/
day
(MRID
00146801).
All
animals
survived
to
scheduled
termination.
Clinical
signs
of
toxicity
in
high
dose
animals
included
anorexia,
emesis,
and
diarrhea.
Absolute
body
weights
for
females
and
food
consumption
for
males
and
females
were
not
affected
by
treatment.
Body
weights
of
the
high
dose
males
were
less
than
those
of
the
controls
throughout
most
of
the
study
with
statistical
significance
attained
occasionally.
Overall
weight
gains
by
the
high
dose
males
and
females
were
67%
and
82%,
respectively,
of
the
control
levels.
No
treatment
related
ophthalmological
lesions,
changes
in
urinalysis
parameters,
or
microscopic
lesions
were
Tebuthiuron
(105501)
RED
Toxicology
Chapter
10
noted
and
gross
necropsy
was
unremarkable.
Thrombocyte
counts
were
significantly
(p
#
0.05)
increased
in
high
dose
males
at
6
and
12
months
as
compared
with
the
controls.
Alanine
aminotransferase
(ALT)
levels
were
increased
in
males
after
1
month
and
in
females
after
3
months
to
186
529%
and
228
407%,
respectively,
of
the
control
group
levels.
In
addition,
alkaline
phosphatase
(AP)
levels
in
males
were
increased
to
283
408%
of
the
control
levels
at
6
and
12
months.
Statistical
significance
was
not
attained
at
all
timepoints
for
the
increases
in
enzyme
levels
due
to
large
variability
between
individual
animals.
Absolute
liver
weights
were
significantly
(p
#
0.05)
increased
in
the
high
dose
males
and
females.
No
other
differences
in
absolute
organ
weights
were
found.
Also
for
the
highdose
groups,
significant
(p
#
0.05)
differences
in
organ
weights
relative
to
final
body
weight
included
increased
relative
liver
weights
in
males
and
females,
increased
relative
kidney
weights
in
females,
and
increased
relative
thyroid
weights
in
males.
The
LOAEL
was
established
at
50
mg/
kg/
day
based
on
clinical
signs
(anorexia,
emesis,
and
diarrhea),
decreased
body
weight
gains,
increased
alanine
aminotransferase
and
alkaline
phosphatase
(males
only)
levels,
increased
absolute
and
relative
liver
weights,
increased
relative
kidney
weights
(females
only),
and
increased
relative
thyroid
weights
(males
only).
The
NOAEL
was
established
at
25
mg/
kg/
day.
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
guideline
requirements
for
a
chronic
toxicity
study
in
dogs
[OPPTS
870.4100
(83
1b)]
.
4.6
Carcinogenicity
Adequacy
of
data
base
for
Carcinogenicity:
The
database
for
carcinogenicity
is
considered
inadequate.
The
HIARC
(TXR
No.
0050450,
dated
February
5,
2002)
reevaluated
the
classification
and
concluded
that
the
carcinogenic
potential
of
tebuthiuron
can
not
be
determined
due
to
inadequate
carcinogenicity
studies.
4.6.1
870.4200b
Carcinogenicity
Study
Crl:
CD
1
(ICR)
BR
Mouse
Executive
Summary:
In
a
carcinogenicity
study
(MRID
00020717)
Tebuthiuron
(>
97%
a.
i.,
lot
#
B30
23
149)
was
administered
to
groups
of
80
Harlan
ICR
mice/
sex/
dose
in
pelleted
diet
at
dose
levels
of
400,
800,
or
1600
ppm
(60,
120,
or
240
mg/
kg
/day
based
on
the
default
food
factor
of
0.15)
for
2
years.
The
control
group,
consisting
of
120
males
and
120
females
was
fed
untreated
pelleted
diet.
Animals
were
equally
subdivided
by
dose
and
sex
into
two
substudies;
the
second
substudy
was
started
1
week
after
the
first.
It
should
be
noted
that
animals
were
not
assigned
by
body
weight.
Although
there
was
a
statistically
significant
decrease
(32.4
g,
12%)
in
the
terminal
body
weights
of
high
dose
females
in
one
of
the
substudies
(M9153),
this
is
likely
due
to
the
higher
body
weight
(36.7
g)
of
the
control
females
in
this
substudy.
The
terminal
body
Tebuthiuron
(105501)
RED
Toxicology
Chapter
11
weight
of
the
control
females
in
the
other
substudy
was
34.1
g.
There
were
no
compound
related
effects
on
mortality,
clinical
signs,
hematology
or
clinical
chemistry,
organ
weights,
or
gross
or
microscopic
pathology.
The
LOAEL
for
systemic
toxicity
was
not
established.
The
NOAEL
was
established
at
1600
ppm
(240
mg/
kg/
day).
At
the
doses
tested,
there
was
no
treatment
related
increase
in
tumor
incidence
when
compared
to
that
of
controls.
Dosing
was
not
considered
adequate
based
on
the
absence
of
systemic
effects.
This
carcinogenicity
study
in
Unacceptable/
Guideline
and
does
not
satisfy
guideline
requirements
for
a
carcinogenicity
study
in
the
rat.
4.6.2
870.4300
Carcinogenicity
Study
CD(
SD)
BR
Rats
Executive
Summary:
See
section
4.5.1
(870.4300).
Adequacy
of
the
Dose
Levels
Tested:
At
the
doses
tested,
there
was
no
treatment
related
increase
in
tumor
incidence
when
compared
to
that
of
controls.
Dosing
was
not
considered
adequate
based
on
the
absence
of
systemic
effects.
4.7
Mutagenicity
Adequacy
of
data
base
for
Mutagenicity:
The
database
for
mutagenicity
is
considered
adequate.
The
submitted
test
battery
satisfies
the
Pre
1991
mutagenicity
initial
testing
battery
guidelines.
There
is
no
evidence
of
gene
mutations
in
bacteria
or
mammalian
cells,
chromosome
aberrations
in
mammalian
cells
or
unscheduled
DNA
syntheses
in
cultured
rat
hepatocytes.
No
further
testing
is
required
at
this
time.
Gene
Mutation
870.5100
Bacterial
reverse
gene
mutation
assay
MRID
00141691
Acceptable/
Guideline
In
a
reverse
gene
mutation
assay
in
bacteria,
S.
typhimurium
strains
TA98,
TA100,
TA1535,
TA1537,
and
TA1538
were
exposed
to
Tebuthiuron
(98.0%,
lot
number
X
35920)
in
dimethylsulfoxide
(DMSO)
at
concentrations
of
100,
500,
1000,
2500,
or
5000
:g/
plate
in
the
presence
and
absence
of
mammalian
metabolic
activation
(S9
mix).
Triplicate
plates
were
utilized
for
each
test
concentration.
Tebuthiuron
was
tested
up
to
the
limit
dose.
No
increase
in
mutant
frequency
was
noted
in
any
strain
with
or
without
metabolic
activation.
The
solvent
and
positive
control
values
were
appropriate
in
the
respective
strains.
There
was
no
evidence
of
induced
mutant
colonies
over
background
in
strains
TA98,
TA100,
TA1535,
TA1537
and
TA1538
with
or
without
S9
activation.
Tebuthiuron
(105501)
RED
Toxicology
Chapter
12
870.5100
Bacterial
reverse
gene
mutation
assay
MRID
00141690
Acceptable/
Guideline
In
a
reverse
gene
mutation
assay
in
bacteria,
S.
typhimurium
strains
G46,
TA1535,
TA100,
C3076,
TA1537,
D3052,
TA1538,
and
TA98
and
E.
coli
strains
WP2
and
WP2
uvrA
were
exposed
to
tebuthiuron
(98.0%,
lot
number
X
35920)
in
dimethylsulfoxide
(DMSO)
over
a
concentration
range
of
0.1
to
1000
:g/
mL,
in
a
gradient
plate
assay,
in
the
presence
and
absence
of
mammalian
metabolic
activation
(S9
mix).
No
increase
in
mutant
frequency
was
noted
in
any
S.
typhimurium
or
E.
coli
tester
strain
with
or
without
metabolic
activation.
The
solvent
and
positive
control
values
were
appropriate
in
the
respective
strains.
There
was
no
evidence
of
induced
mutant
colonies
over
background
in
S.
typhimurium
strains
G46,
TA1535,
TA100,
C3076,
TA1537,
D3052,
TA1538,
and
TA98
and
E.
coli
strains
WP2
and
WP2
uvrA
with
or
without
S9
activation.
870.5300
In
vitro
mammalian
cell
gene
mutation
MRID
00145041
Acceptable/
Guideline
In
a
mammalian
cell
gene
mutation
assay
in
vitro,
cultures
of
mouse
lymphoma
L5178Y
TK+/
cells
were
exposed
to
Tebuthiuron
(98.0%,
lot
No.
X
35920)
in
dimethylsulfoxide
at
concentrations
of
100,
200,
300,
400,
500,
600,
700,
or
800
:g/
mL
in
an
initial
assay
the
absence
of
mammalian
metabolic
activation
(S9
mix),
and
at
concentrations
of
10,
100,
200,
300,
400,
500,
750,
or
1000
:g/
mL
in
an
initial
assay
in
the
presence
of
S9
mix.
Due
to
cytotoxicity,
the
nonactivated
assay
was
repeated
at
concentrations
of
10,
100,
200,
400,
500,
600,
700,
and
800
:g/
mL,
and
the
activated
assay
was
repeated
at
concentrations
of
1,
10,
100,
200,
400,
500,
600,
or
700
:g/
mL.
Tebuthiuron
technical
was
tested
up
to
concentrations
limited
by
cytotoxicity.
Relative
growth
ranged
from
57%
to
13%
(at
100
to
800
:g/
mL)
in
the
absence
of
metabolic
activation
in
the
initial
assay
and
from
28%
to
6%
(at
10
to
750
:g/
mL)
in
the
presence
of
metabolic
activation
in
the
initial
assay.
In
the
initial
nonactivated
assay,
mutation
indices
of
2.0
and
2.4
were
detected
at
700
and
800
:g/
mL,
respectively.
In
a
repeat
nonactivated
assay,
mutation
indices
of
2.0,
2.0,
and
2.7
occurred
at
200,
400,
and
500
:g/
mL,
respectively.
Mutations
were
not
induced
at
any
concentration
with
activation.
The
ethyl
methane
sulfonate
(without
S9)
and
3
methylcholanthrene
(with
S9
mix)
positive
controls
responded
appropriately.
Tebuthiuron
was
considered
weakly
mutagenic
in
the
absence
of
metabolic
activation.
No
evidence
of
an
increased
mutant
frequency
was
observed
in
the
presence
of
metabolic
activation.
Tebuthiuron
(105501)
RED
Toxicology
Chapter
13
Cytogenetics
870.5375
In
vitro
mammalian
cell
chromosome
aberration
MRID
41134101
Acceptable/
Guideline
In
a
mammalian
chromosome
aberration
assay,
Chinese
Hamster
Ovary
(CHO)
cell
cultures
were
exposed
to
Tebuthiuron
(99.08%,
lot
number
729AS7)
in
dimethylsulfoxide
at
concentrations
of
0,
1650,
1800,
or
1950
:g/
mL
for
4
hours
in
the
absence
of
exogenous
metabolic
activation
(S9
mix)
or
to
1350,
1450,
or
1550
:g/
mL
for
4
hours
in
the
presence
of
activation
(followed
by
an
additional
19
hour
incubation
in
fresh
medium).
Tebuthiuron
was
tested
up
to
concentrations
limited
by
cytotoxicity.
A
preliminary
cytotoxicity
test
showed
survival
ranging
from
15%
at
2285
:g/
mL
to
115%
at
1000
:g/
mL
under
nonactivated
conditions
and
39%
at
1750
:g/
mL
and
55%
at
1500
:g/
mL.
A
significant
(p<
0.01)
increase
in
the
percent
of
cells
with
aberrations
was
noted
in
nonactivated
cultures
at
1950
:g/
mL
(15
&19%
for
treated
duplicate
cultures
vs.
5%
for
vehicle
controls)
and
activated
cultures
at
1550
:g/
mL
(15
&18%
for
treated
duplicate
cultures
vs.
5
6%
for
vehicle
controls).
The
predominant
types
of
aberrations
were
chromosome
and
chromatid
breaks.
No
significant
increases
were
observed
at
lower
concentrations;
however,
rare
complex
aberrations,
such
as
triradials,
quadriradials
and
complex
rearrangements
were
noted,
providing
further
support
for
clastogenicity.
Positive
control
values
were
acceptable.
There
was
evidence
of
an
increase
in
structural
chromosomal
aberrations
over
background
in
the
presence
and
absence
of
metabolic
activation.
Other
Genotoxicity
870.5550
Unscheduled
DNA
synthesis
in
mammalian
cell
culture
MRID
40750901
Acceptable/
Guideline
In
an
unscheduled
DNA
synthesis
assay,
primary
rat
hepatocyte
cultures
were
exposed
to
Tebuthiuron
(99.1%
a.
i.;
Lot
No.
729AS7)
in
dimethylsulfoxide
at
eight
concentrations
ranging
from
300
to
800
:g/
mL
for
20
hours.
Tebuthiuron
was
tested
to
the
limit
of
cytotoxicity
(cytotoxicity
was
observed
at
$900
:g/
mL).
UDS
activity
was
evaluated
at
concentrations
up
to
800
:g/
mL
and
there
was
no
evidence
of
induction
of
UDS.
The
solvent
(1%
DMSO)
and
positive
control
(N
methyl
N'
nitrosoguanidine
1
:g/
mL
and
2
acetoaminofluorene
0.05
:g/
mL)
values
were
appropriate.
There
was
no
evidence
that
unscheduled
DNA
synthesis,
as
determined
by
radioactive
tracer
procedures
[nuclear
silver
grain
counts]
was
induced.
4.8
Neurotoxicity
Adequacy
of
data
base
for
Neurotoxicity:
No
acute
or
subchronic
neurotoxicity
studies
on
Tebuthiuron
are
available.
Evaluation
of
subchronic,
chronic
and
reproduction
toxicity,
did
not
reveal
any
treatment
related
effects
on
the
central
or
peripheral
nervous
system
of
mice,
rats,
or
rabbits.
No
changes
in
clinical
signs,
brain
weights,
gross
necropsy
results
or
histopathological
results
suggested
any
part
of
the
nervous
system
as
a
target
organ.
However,
the
HIARC
meeting
on
December
13,
2001
and
January
17,
2002
determined
that
a
developmental
neurotoxicity
study
should
be
held
in
reserve,
pending
submission
of
a
developmental
toxicity
study
in
the
rabbit
(TXR
No.
0050450,
dated
Tebuthiuron
(105501)
RED
Toxicology
Chapter
14
February
5,
2002).
4.8.1
870.6100
Delayed
Neurotoxicity
Study
Hen
This
study
is
not
required.
4.8.2
870.6200a
Acute
Neurotoxicity
Screening
Battery
This
study
is
not
required.
4.8.3
870.6200b
Subchronic
Neurotoxicity
Screening
Battery
This
study
is
not
required.
4.8.4
870.6300
Developmental
Neurotoxicity
Study
The
requirement
for
this
study
is
being
held
in
reserve.
4.9
Metabolism
Adequacy
of
data
base
for
metabolism:
The
data
base
for
metabolism
is
considered
complete
and
no
additional
studies
are
required
at
this
time.
4.9.1
870.7485
Metabolism
Rat
Executive
Summary:
In
a
metabolism
study
(MRID
42711701,
43129701),
male
and
female
Fischer
344
rats
were
dose
with
14
C
tebuthiuron
at
a
single
low
oral
dose
(10
mg/
kg),
a
repeated
low
oral
dose
(10
mg/
kg
x
14
days),
or
a
single
high
dose
(100
mg/
kg).
Absorption
was
complete
at
both
the
low
and
high
dose.
Terminal
distribution
data
showed
no
significant
amounts
of
residual
radioactivity
in
any
tissue
examined,
but
the
skin
showed
the
highest
amounts
relative
to
other
tissues.
Excretion
was
rapid
at
both
the
low
and
high
dose
levels
in
both
sexes,
but
was
delayed
during
the
first
12
hours
postdose
indicating
saturation
of
biotransformation
or
excretion.
From
HPLC
and
mass
spectral
analysis
of
urine
samples,
6
metabolites
of
tebuthiuron
were
identified.
The
major
metabolite
was
identified
as
109OH
and/
or
104
OH,
both
hydroxylated
metabolites
of
tebuthiuron.
This
metabolite
composed
between
39.6
60.3%
of
the
administered
dose
in
0
24
hour
urine
of
male
and
female
rats.
The
second
most
abundant
metabolite
was
identified
as
metabolite
106
of
tebuthiuron.
This
comprised
between
9
15%
of
the
administered
dose
in
0
24
hour
urine
of
low
dose
rats,
and
between
55.6%
and
57.3%
of
the
administered
dose
for
male
and
female
rats,
respectively.
Two
other
metabolites
identified,
104/
109
and
103
OH,
comprised
between
2
10%
of
the
administered
dose
in
male
and
female
0
24
hour
urine.
Feces
contained
minor
amounts
of
104
OH
and
109
OH,
accounting
for
an
average
of
3.5%
of
the
administered
dose.
4.10
Special
Studies
None
5
TOXICITY
ENDPOINT
SELECTION
Tebuthiuron
(105501)
RED
Toxicology
Chapter
15
See
Section
9.2
for
Endpoint
Selection
Table
5.1
Dermal
Absorption
No
study
available.
5.2
Classification
of
Carcinogenic
Potential
5.2.1
Conclusions
and
Classification
of
Carcinogenic
Potential
The
HIARC
(TXR
No.
0050450,
dated
February
5,
2002)
reevaluated
the
classification
and
concluded
that
the
carcinogenic
potential
of
tebuthiuron
can
not
be
determined
due
to
inadequate
carcinogenicity
studies.
5.2.2
Quantification
of
Carcinogenic
Potential
Not
applicable
6
FQPA
CONSIDERATIONS
6.1
Special
Sensitivity
to
Infants
and
Children
The
toxicological
database
is
inadequate
for
FQPA
assessment.
The
developmental
toxicity
study
in
the
rabbit
is
unacceptable
for
the
determination
of
susceptibility
to
the
fetuses
due
to
in
utero
tebuthiuron
exposure.
However,
there
is
an
adequate
developmental
toxicity
study
in
the
rat
and
a
two
generation
reproductive
toxicity
study
in
the
rat
to
assess
the
susceptibility
of
fetuses/
offspring
to
tebuthiuron.
There
is
no
qualitative/
quantitative
evidence
of
increased
susceptibility
in
2
generation
reproduction
study
in
the
rat
or
the
developmental
toxicity
study
in
the
rat.
In
the
developmental
toxicity
study
in
the
rabbit,
no
maternal
or
developmental
toxicity
was
observed
at
the
highest
dose
tested.
Because
there
was
no
toxicity
observed
at
the
highest
dose
tested,
susceptibility
could
not
be
ascertained
and
the
HIARC
concluded
that
a
new
developmental
toxicity
in
the
rabbit
is
needed..
6.2
Recommendation
for
a
Developmental
Neurotoxicity
Study
The
FQPA
Committee
reserved
the
requirement
of
a
developmental
neurotoxicity
study
pending
submission
of
a
developmental
toxicity
study
in
rabbits.
7
OTHER
ISSUES
None
8
REFERENCES
00020662
Todd,
G.
C.;
Gibson,
W.
R.;
Kiplinger,
G.
F.
(1972)
The
Toxicological
Evaluation
of
EL
103
in
Rats
for
3
Months.
(Unpublished
study
received
Mar
13,
1973
under
1471
97;
submitted
by
Elanco
Products
Co.,
Div.
of
Eli
Lilly
and
Co.,
Tebuthiuron
(105501)
RED
Toxicology
Chapter
16
Indianapolis,
Ind.;
CDL:
006422
G)
00020663
Todd,
G.
C.;
Gibson,
W.
R.;
Kiplinger,
G.
F.
(1972)
The
Toxicological
Evaluation
of
EL
103
in
Dogs
for
3
Months.
(Unpublished
study
received
Mar
13,
1973
under
1471
97;
submitted
by
Elanco
Products
Co.,
Div.
of
Eli
Lilly
and
Co.,
Indianapolis,
Ind.;
CDL:
006422
H)
00020644
Todd,
G.
C.,
Markham,
J.
K.,
Adams,
E.
R.,
Owen,
N.
V.,
Gossett,
F.
O.,
and
Morton,
D.
M.
(1975)
A
teratology
study
with
EL
103
in
the
rabbit.
Toxicology
Division,
Lilly
Research
Laboratories,
Greenfield,
IN.
Study
No.
B
7014.
April
1975.
Unpublished.
00020714
Todd,
G.,
W.
Gibson,
D.
Hoffman,
et
al.
1976.
The
toxicological
evaluation
of
tebuthiuron
(EL
103)
in
rats
for
two
years.
Studies
R
603
and
R
613.
Toxicology
Division,
Lilly
Research
Laboratories,
Greenfield,
IN,
November,
1976.
Unpublished.
00020717
Todd,
G.
C.;
Gibson,
W.
R.;
Hoffman,
D.
G.;
et
al.
(1976)
The
Toxicological
Evaluation
of
Tebuthiuron
(EL
103)
in
Mice
for
Two
Years:
Toxicology
Report
#
8.
(Unpublished
study
received
Dec
1,
1976
under
1471
EX
43;
submitted
by
Elanco
Products
Co.,
Div.
of
Eli
Lilly
and
Co.,
Indianapolis,
Ind.;
CDL:
230139
D)
00020803
Todd,
G.
C.,
Markham,
J.
K.,
Adams,
E.
R.,
Owen,
N.
V.,
Gibson,
W.
R.,
and
Kiplinger,
G.
F.
(1972)
Rat
teratology
study
with
EL
103.
The
Lilly
Toxicology
Laboratories,
Eli
Lilly
and
Company,
Greenfield,
IN.
Laboratory
Study
No.
R632
September,
1972.
Unpublished.
00090108
Adams,
E.
R.,
N.
Owen,
and
J.
Hoyt.
1981.
A
two
generation
reproduction
study
with
tebuthiuron
(Compound
75503)
in
the
Wistar
rat.
Lilly
Research
Laboratories,
Greenfield,
IN.
November,
1981.
Study
numbers
R03780
and
R08780.
Unpublished
00141691
Rexroat,
M.
A.,
Todd,
G.
C.
(1984).
The
effect
of
Tebuthiuron
(Lilly
Compound
75503)
on
the
induction
of
reverse
mutations
in
Salmonella
typhimurium
using
the
Ames
test.
Lilly
Research
Laboratories,
Greenfield,
IN.
Study
No.
840326AMS655.
April,
1984.
Unpublished
00145041
Oberly,
T.
J,
Bewsey,
B.
J.,
Todd,
G.
C.
(1984).
The
effect
of
Tebuthiuron
(Lilly
Compound
75503)
on
the
induction
of
forward
mutation
at
the
thymidine
kinase
locus
of
L5178Y
mouse
lymphoma
cells.
Lilly
Research
Laboratories,
Greenfield,
IN.
Study
Nos.
840410
MLA655,
84060MLA655,
840612MLA655.
Unpublished.
00146801
Todd,
G.
(1985).
The
toxicity
evaluation
of
tebuthiuron
(Lilly
compound
75503)
to
Beagle
dogs
for
one
year.
Lilly
Research
Laboratories,
Greenfield,
IN.
Laboratory
Study
No.
D04283.
February
1985.
MRID.
Unpublished.
00149733
Brown,
G.
(1985)
Subchronic
(21
Day)
Dermal
Toxicity
Study
in
New
Zealand
White
Rabbits
with
Technical
Tebuthiuron:
Study
B01484.
Unpublished
study
Tebuthiuron
(105501)
RED
Toxicology
Chapter
17
prepared
by
Lilly
Research
Laboratories.
211
p.
00160796
Negilski,
D.;
McGrath,
J.;
Young,
S.
(1986)
Reply
to
U.
S.
EPA
Recommendation
To
Upgrade
the
Current
21
day
Dermal
Toxicity
Study
(BO1484)
of
Technical
Tebuthiuron
with
Additional
Doses
to
Establish
a
Systemic
No
effect
Level.
Unpublished
study
prepared
by
Eli
Lilly
and
Co.
18
p.
40485801
Todd,
G.
C.
and
Higdon,
G.
L.
(1972)
A
supplementary
report
of
a
rat
teratology
study
with
tebuthiuron
(EL
103,
compound
75503).
Toxicology
Division,
Lilly
Research
Laboratories,
Greenfield,
IN.
Laboratory
Study
No.
R
632.
September,
1972.
Unpublished.
40750901
Negilski.
D.
S,
Garriot,
M.
L.,
Yount,
D.
J.
(1988)
.
The
effect
of
Tebuthiuron
(EL
103,
Compound
75503)
on
the
induction
of
DNA
synthesis
in
primary
cultures
of
adult
rat
hepatocytes.
Eli
Lilly
and
Company,
Greenfield,
IN.
Study
Nos.
880510UDS0655
and
880517
UDS0655.
Unpublished.
40776301
Negilski,
D.
S.
and
Higdon,
G.
L.
(1988)
A
supplementary
report
in
support
of
a
teratology
study
with
tebuthiuron
(EL
103,
Compound
75503)
in
the
rabbit.
Toxicology
Division,
Lilly
Research
Laboratories,
Greenfield,
IN.
Study
No.
B7014
June
8,
1988.
Unpublished.
40870101
Negilski,
D.;
Todd,
G.
(1988)
A
Supplemental
Inventory
of
Selected
Tissues
from
Rats
Given
Diets
Containing
Tebuthiuron
(...)
for
Two
Years:
Project
ID:
R
603
and
R
613.
Unpublished
study
prepared
by
Lilly
Research
Laboratories.
10
p.
41122401
Megilski,
D.
S.,
Rutherford,
B.
S.,
and
Higdon,
G.
L.
(1989)
A
supplementary
report
for
a
rabbit
teratology
study
(B
7014)
with
tebuthiuron
(EL
103,
Compound
75503)
A
response
to
the
U.
S.
EPA's
request
for
certain
additional
information
to
upgrade
the
rabbit
teratology
study
from
core
supplementary
to
core
minimum.
Toxicology
Division,
Lilly
Research
Laboratories,
Greenfield,
IN.
Study
No.
B
7014.
March
8,
1989.
Unpublished.
41134101
Negilski,
D.
S.,
Garriot,
M.
L.,
Kindig,
D.
E.
F.
(1989)
The
effect
of
tebuthiuron
(EL
103,
Compound
075503)
on
the
in
vitro
induction
of
chromosomal
aberrations
in
Chinese
Hamster
Ovary
cells.
Lilly
Research
Laboratories,
Greenfield,
IN,
Study
Nos.
890111CTX655,
890125CTX655,
890201CAB655,
890228CAB655.
April
12,
1989.
Unpublished.
42711701
Eschbach,
J.;
Hackett,
D.
(1993)
Absorption,
Distribution
and
Elimination
of
(Carbon
14)
Tebuthiuron
in
Rats:
Lab
Project
Number:
DR
0189
9383
001.
Unpublished
study
prepared
by
Bio/
dynamics,
Inc.
107
p.
43129701
Eschbach,
J.;
Hackett,
D.
(1994)
Absorption,
Distribution
and
Elimination
of
(carbon
14)
Tebuthiuron
in
Rats:
Addendum:
Lab
Project
Number:
DR/
0189/
9383/
001.
Unpublished
study
prepared
by
Bio/
dynamics,
Inc.
10
p.
USEPA
Memorandum:
Tebuthiuron
oncogenicity
studies,
HED
Project
No.
9
0927,
Tebuthiuron
(105501)
RED
Toxicology
Chapter
18
Caswell
No.
366AA.
From
Quang
Q.
Bui,
Head,
Review
Section
I,
Tox
BranchHFAS
HED
to
Robert
Taylor,
PM,
#
25,
Registration
Division,
November
30,
1988
(TXR
No.:
007374)
USEPA
Memorandum:
Tebuthiuron:
Report
of
the
Hazard
Identification
Assessment
Review
Committee,
February
5,
2002
(TXR
No
0050450)
USEPA
Memorandum:
Tebuthiuron:
Report
of
the
FQPA
Safety
Factor
Committee,
February
12,
2002
(TXR
No.
0050466)
Tebuthiuron
(105501)
RED
Toxicology
Chapter
19
9
APPENDICES
Tables
for
Use
in
Risk
Assessment
9.1
Toxicity
Profile
Summary
Tables
9.1.1
Acute
Toxicity
Table
See
Section
4.1
9.1.2
Subchronic,
Chronic,
and
Other
Toxicity
Table
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
870.3100
90
Day
oral
toxicityrat
00020662
(1972)
Acceptable/
Guideline
0,
20,
50,
125
mg/
kg/
day
NOAEL
=
50
mg/
kg/
day
LOAEL
=
125
mg/
kg/
day,
based
on
decreased
body
weight,
increased
relative
liver,
kidney,
gonads,
spleen
(males
only),
and
prostate
and
slight
vacuolization
of
pancreatic
acinar
cells.
870.3150
90
Day
oral
toxicitydog
00020663
(1972)
Acceptable/
Guideline
0,
12.5,
25,
50
NOAEL
=
25
mg/
kg/
day
LOAEL
=
50
mg/
kg/
day,
based
on
decrease
in
body
weight
and
increased
alkaline
phosphatase
activity.
870.3200
21/
28
Day
dermal
toxicity
rabbit
00149733
(1985)
00160796
(1986)
Acceptable/
Guideline
0,
1000
mg/
kg/
day
NOAEL
=
1000
mg/
kg/
day
(limit
dose)
870.3250
90
Day
dermal
toxicity
No
study
available
N/
A
870.3465
90
Day
inhalation
toxicity
No
study
available
N/
A
870.4100
[83
1(
b)]
1
Year
Feeding
Study
Dog
00146801
(1985)
Acceptable/
Guideline
0,
12.5,
25,
50
mg/
kg/
day
NOAEL=
25
mg/
kg/
day
LOAEL
=
50
mg/
kg/
day
based
on
clinical
signs,
decreased
body
wt,
increased
ALT
and
ALP
(males
only),
increased
absolute
and
relative
livers
and
relative
thyroid
wt,
(males
only)
wt,
and
increased
absolute
liver
wt.
870.4200
[83
2
(b)]
Oncogenicity
Study
Mouse
00020717
(1986)
Unacceptable/
Guideline
0,
60,
120,
240
mg/
kg/
day
NOAEL=
240
mg/
kg/
day
LOAEL
=
Not
achieved
Histopathology:
None
observed
at
doses
tested,
doses
not
high
enough
to
assess
carcinogenicity.
Tebuthiuron
(105501)
RED
Toxicology
Chapter
20
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
870.4300
[83
5(
a)]
Combined
Chronic
Toxicity/
Carcinogenicity
Study
Rat
00020714
(1976)
00098190
(1981)
40870101
(1988)
Unacceptable/
Guideline
0,
20,
40,
80
mg/
kg/
day
NOAEL
=
40
mg/
kg/
day,
females
80
mg/
kg/
day
males
LOAEL
=
80
mg/
kg/
day,
based
on
decreased
terminal
body
weight
in
females
not
established
in
males
Histopathology:
None
observed
at
doses
tested,
doses
not
high
enough
to
assess
carcinogenicity.
870.3700
[83
3(
a)]
Developmental
Toxicity
Study
Rat
00020803
(1972)
40485801
(1972)
Acceptable/
Guideline
0,
37,
72,
110
mg/
kg/
day
Maternal
Systemic
NOAEL=
72
mg/
kg/
day
LOAEL
=
110
mg/
kg/
day)
based
on
decreased
body
weight
gains
and
food
consumption.
Developmental
NOAEL
=
110
mg/
kg/
day
LOAEL
=
not
established
870.3700
[83
3(
b)]
Developmental
Toxicity
Rabbit
00020644
(1975)
40776301
(1988)
41122401
(1989)
Unacceptable/
Guideline
0,
10,
or
25mg/
kg/
day
Maternal
Systemic
NOAEL=
25
mg/
kg/
day
LOAEL
=
not
established
Developmental
NOAEL
=
25
mg/
kg/
day
LOAEL
=
not
established
870.3800
[83
4]
2
Generation
Reproduction
Rat
00090108
(1981)
Acceptable/
Guideline
%%
0,
7,
14,
and
26
mg/
kg/
day
&&
7,
14,
and
30
mg/
kg/
day,
Systemic
NOAEL=
14
mg/
kg/
day
LOAEL
=
30
mg/
kg/
day,
based
on
deceased
in
body
weight
and
weight
gain
in
F1
females.
Parental
effect
levels
were
not
established
for
adult
male
rats
in
this
study.
Reproductive
NOAEL
=
30
mg/
kg/
day
LOAEL
=
not
established
Offspring
NOAEL
=
30
mg/
kg/
day
LOAEL
=
not
established
870.7600
(85
2)
Dermal
Penetration
Rat
No
study
available
N/
A
Tebuthiuron
(105501)
RED
Toxicology
Chapter
21
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
870.7485
(85
1)
Metabolism
Study
Rat
42711701
(1993)
43129701
(1994)
Acceptable/
Guideline
10
or
100
mg/
kg,
1
day
10
mg/
kg/
day
for
14
days
Terminal
distribution
data
showed
no
significant
amounts
of
residual
radioactivity
in
any
tissue
examined,
but
the
skin
showed
the
highest
amounts
relative
to
other
tissues.
Excretion
was
rapid
at
both
the
low
and
high
dose
levels
in
both
sexes,
but
was
delayed
during
the
first
12
hours
post
dose,
indicating
saturation
of
biotransformation
or
excretion.
Six
metabolites
of
tebuthiuron
were
identified.
The
major
metabolite
in
0
24
hour
urine
of
male
(58.3%)
and
female
(62.1%)
rats
was
identified
as
hydroxylated
tebuthiuron
metabolites
(#
109
OH
and
/or
#104
OH).
The
second
most
abundant
metabolite
was
identified
as
metabolite
106
of
tebuthiuron.
This
comprised
between
9
15%
of
the
administered
dose
in
0
24
hour
urine
of
low
dose
rats,
and
between
1
10%
of
the
administered
dose
in
high
dose
rats.
Two
other
metabolites
identified,
104/
109
and
103
OH,
.comprised
between
2
10%
of
the
administered
dose
in
male
and
female
0
24
hour
urine.
Feces
contained
minor
amounts
of
104
OH
and
109
OH,
accounting
for
an
average
of
3.5%
of
the
administered
dose.
Tebuthiuron
(105501)
RED
Toxicology
Chapter
22
aPAD
aRfD
FQPA
SF
=
cPAD
cRfD
FQPA
SF
=
9.2
Summary
of
Toxicological
Dose
and
Endpoints
for
Tebuthiuron
for
Use
in
Human
Risk
Assessment
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
1
FQPA
SF
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
females
13
50
years
of
age
NOAEL
=
25
mg/
kg/
day
UF
=
100
Acute
RfD
=
0.25
mg/
kg/
day
FQPA
SF
2
=3
=
0.083
mg/
kg/
day
Developmental
Toxicity
Study
Rabbit
NOAEL
of
25
mg/
kg/
day.
LOAEL
not
established
A
range
finding
study
showed
increased
early
resorptions
at
50
mg/
kg/
day
Acute
Dietary
general
population
including
infants
and
children
N/
A
N/
A
No
appropriate
effects
attributed
to
a
single
exposure
was
identified.
Chronic
Dietary
all
populations
NOAEL=
14
mg/
kg/
day
UF
=
100
Chronic
RfD
=
0.14
mg/
kg/
day
FQPA
SF
3
=
1
=
0.14
mg/
kg/
day
Two
generation
reproduction
study
in
the
rat
LOAEL
=
30
mg/
kg/
day,
based
on
decreased
body
weight
and
feed
consumption
in
F1
females
Toxicological
endpoints
for
occupational/
residential
exposure
risk
assessments
were
not
selected
since
tebuthiuron
is
scheduled
for
a
Tolerance
Reassessment
Eligibility
Decision
(TRED)
1
UF
=
uncertainty
factor,
FQPA
SF
=
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
PAD
=
population
adjusted
dose
(a
=
acute,
c
=
chronic)
RfD
=
reference
dose
2
Because
there
is
a
data
gap
for
assessing
susceptibility
of
fetuses
following
in
utero
exposure
a
FQPA
safety
factor
of
3x
will
be
used.
3
Because
there
was
no
susceptibility
identified
in
the
2
generation
rat
reproduction
study
(a
long
term
study).
the
FQPA
safety
factor
will
be
removed
(1x).
| epa | 2024-06-07T20:31:42.611509 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0146-0005/content.txt"
} |
EPA-HQ-OPP-2002-0146-0006 | Supporting & Related Material | "2002-06-25T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
April
3,
2002
SUBJECT:
Tebuthiuron
Acute
and
Chronic
Dietary
Exposure
Assessments
for
the
Tolerance
Reassessment
Eligibility
Decision
(TRED);
PC
codes
105501;
DP
Barcode
D281821.
FROM:
Sheila
Piper,
Chemist
Chemistry
and
Exposure
Branch
Health
Effects
Division
(7509C)
THROUGH:
F.
B.
Suhre,
Branch
Senior
Scientist
Chemistry
and
Exposure
Branch
Health
Effects
Division
(7509C)
and
Sherrie
Kinard,
Chemist
Douglas
Dotson,
Chemist
Dietary
Exposure
Science
Advisory
Council
(DeSAC)
Health
Effects
Division
(7509C)
TO:
Paula
Deschamp,
Risk
Assessor
Reregistration
Branch
II
Health
Effects
Division
(7509C)
and
Wilhelmena
Livingston,
Chemical
Review
Manager
Special
Review
Branch
Special
Review
and
Reregistration
Division
(7508C)
The
purpose
of
this
memorandum
is
to
summarize
the
results
of
the
dietary
risk
assessment
for
the
general
U.
S.
population
(chronic
only)
and
females
13
50
years
(acute)
resulting
from
exposure
to
tebuthiuron
through
food.
This
risk
assessment
is
an
updated
risk
analysis
that
has
been
conducted
for
tebuthiuron.
The
most
recent
dietary
risk
assessment
was
conducted
by
J.
M.
Winterseen
(09/
01/
93).
DP
Barcode:
D281821
Dietary
exposure
assessment
/
1
Tebuthiuron
/
105501
1
aPAD/
cPAD
=
acute/
chronic
Population
Adjusted
Dose
=
Acute
or
Chronic
RfD
FQPA
Safety
Factor
1
EPA
Reviewer:
Sheila
Piper
,
Date
April
3,
2002
STUDY
TYPE:
Tebuthiuron
Acute
and
Chronic
Dietary
Exposure
Assessments
for
the
Tolerance
Reregistration
Eligibility
Decision
(TRED)
PC
codes
105501;
DP
Barcode
D281821.
ACTIVE
INGREDIENT:
Tebuthiuron
SYNONYMS:
Spike
RESIDUE
OF
CONCERN:
The
residues
of
concern
in
livestock
commodities
are
tebuthiuron
and
its
metabolites
104,
106,
108,
and
109;
the
terminal
residues
of
concern
in
milk
are
tebuthiuron
and
metabolites
104,
104(
OH),
106,
109
and
109(
OH).
Executive
Summary
A
Tier
2
acute
and
a
chronic
dietary
risk
assessment
were
conducted
for
all
supported
currently
registered
tebuthiuron
food
uses.
Dietary
risk
estimates
are
provided
for
the
general
U.
S.
population
(chronic
only)
and
females
13
50
(acute).
This
assessment
concludes
that
for
all
included
commodities,
the
acute
risk
estimates
are
below
the
Agency's
level
of
concern
(<
100%
aPAD
1
)
at
the
95
th
exposure
percentile
for
females
13
50
years
(<
1%
of
the
aPAD).
This
assessment
also
concludes
that
for
all
included
commodities,
the
chronic
risk
estimates
are
below
the
Agency's
level
of
concern
(<
100%
cPAD
1
)
for
the
general
U.
S.
population
(<
1%
of
the
cPAD)
and
all
population
subgroups.
I.
Introduction
Exposure
to
pesticides
can
occur
through
food,
water,
residential
and
occupational
means.
Risk
assessment
incorporates
both
exposure
and
toxicity
of
a
given
pesticide.
The
risk
is
expressed
as
a
percentage
of
a
dose
that
could
be
expressed
as
a
daily
or
a
long
term
dose,
that
poses
no
unreasonable
adverse
effects.
This
is
called
the
population
adjusted
dose
(PAD),
and
is
expressed
as
%PAD.
References
are
available
on
the
DP
Barcode:
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exposure
assessment
/
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/
105501
2
EPA/
pesticides
web
site
which
discuss
the
acute
and
chronic
risk
assessments
in
more
detail:
"Available
Information
on
Assessing
Exposure
from
Pesticides,
A
User's
Guide",
6/
21/
2000,
web
link:
http://
www.
epa.
gov/
fedrgstr/
EPA
PEST/
2000/
July/
Day
12/
6061.
pdf
;
or
see
SOP
99.6,
8/
20/
99.
The
purpose
of
this
memorandum
is
to
summarize
the
results
of
the
dietary
risk
assessment
for
the
U.
S.
population
(chronic
only)
and
females
13
50
(acute)
resulting
from
exposure
to
tebuthiuron
through
food.
This
risk
assessment
is
an
updated
risk
analysis
that
has
been
conducted
for
tebuthiuron.
The
most
recent
dietary
exposure
analysis
was
conducted
by
J.
M.
Winterseen
(09/
01/
93).
II.
Toxicological
Information
HED
has
completed
the
dietary
risk
assessment
for
tebuthiuron
on
the
deliberations
of
the
Hazard
Identification
Assessment
Review
Committee
(HIARC)
and
hazard
endpoints
have
been
selected
for
both
acute
(one
day)
and
chronic
(long
term)
exposure
intervals
(Memorandum:
R.
Fricke
dated
February
5,
2002).
On
December
13,
2001
and
January
17,
2002
the
HIARC
evaluated
the
results
of
a
rabbit
developmental
toxicity
study
and
its
impact
on
the
Food
Quality
Protection
Act
(FQPA)
assessment
and
toxicity
endpoint
selection
for
tebuthiuron.
An
appropriate
endpoint
attributable
to
a
single
dose
was
not
available
in
the
database
for
an
acute
reference
dose
(general
population).
An
appropriate
acute
endpoint
(females
13+)
attributable
to
a
single
dose
at
25
mg/
kg/
day
was
selected
for
risk
assessment,
since
there
was
no
dose
response
in
the
observed
early
resorptions.
In
addition,
the
selection
of
the
25
mg/
kg/
day
dose
for
risk
assessment
is
supported
by
the
NOAEL
of
50
mg/
kg/
day
in
a
rabbit
developmental
range
finding
study
with
a
structurally
related
urea.
For
chronic
reference
dose,
the
NOAEL
is
14
mg/
kg/
day
from
the
twogeneration
reproduction
study
based
on
decreased
body
weight,
body
weight
gain
and
food
consumption
in
F1
females
at
30
mg/
kg/
day.
The
acute
and
chronic
hazard
endpoints
selected
for
dietary
exposure
to
tebuthiuron
are
listed
in
Table
1.
In
a
meeting
on
February
4,
2002,
the
FQPA
Safety
Factor
Committee
recommended
that
the
10X
FQPA
Safety
Factor
(as
required
by
the
Food
Quality
Protection
Act
of
August
3,
1996)
be
reduced
to
3X
for
acute
dietary
exposure
(females
13
50)
and
1X
for
chronic
dietary
exposure
(general
population)
when
assessing
the
potential
dietary
risks
posed
by
tebuthiuron
use
(C.
Christensen,
FQPA
memo,
02/
12/
02).
The
basis
and
rationale
for
the
3x
FQPA
safety
factor
for
females
13
50
years
is
due
to
a
data
gap
for
assessing
susceptibility
of
fetuses
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following
in
utero
exposure
to
tebuthiuron.
For
chronic
dietary
exposure
to
the
general
population,
the
FQPA
safety
factor
will
be
reduced
to
1x
because
there
was
no
susceptibility
identified
in
the
2
generation
rat
reproduction
study
(a
long
term
study).
Table
1.
Summary
of
Toxicological
Dose
and
Endpoints
for
Tebuthiuron
for
Use
in
Dietary
Exposure
Assessment
EXPOSURE
SCENARIO
DOSE
(mg/
kg/
day)
ENDPOINT
STUDY
Acute
Dietary
(Females
13
50)
NOAEL=
25
UF
=
100
FQPA=
3X
Increased
post
implantation
loss
and
fetal/
litter
resorptions
at
50
mg/
kg/
day
(LOAEL).
Developmental
Toxicity
Study
in
the
Rabbit
Acute
RfD
(Females
13
50
years
old)
=
0.25
mg/
kg/
day
Acute
PAD
(females
13
50)=
0.083
mg/
kg/
day
Acute
Dietary
(General
Population)
No
appropriate
effects
attributed
to
a
single
exposure
were
identified.
Chronic
Dietary
NOAEL
=
14
UF
=
100
FQPA=
1X
Decreased
body
weight
and
feed
consumption
in
F1
females
at
30
mg/
kg/
day
(LOAEL)
2
Generation
Reproduction
Study
in
the
Rat
Chronic
RfD
=
0.14
mg/
kg/
day
Chronic
PAD
(all
population)=
0.14
mg/
kg/
day
Cancer
No
endpoint
for
carcinogenicity
due
to
inadequate
carcinogenicity
studies
Category
D
or
not
classifiable
as
to
human
carcinogenicity
Rat
and
mouse
carcinogenicity
studies
III.
Residue
Information
Tebuthiuron
[N[
5(
1,1
dimethylethyl)
1,3,4
thiadiazol
2
yl]
N,
N'
dimethylurea]
is
a
relatively
nonselective,
soil
activated
herbicide
registered
for
use
to
control
broadleaf,
woody
weeds,
grasses
and
brush
on
terrestrial
feed
crop
sites
(pastures
and
rangeland).
Pelleted/
tableted
(P/
T)
is
the
only
tebuthiuron
formulation
class
registered
for
use
on
food/
feed
crops.
This
formulation
may
be
applied
preplant,
preemergence,
postemergence,
or
postharvest.
The
registered
mode
of
DP
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application
is
broadcast
using
ground
or
aerial
equipment.
Tolerances
for
residues
of
tebuthiuron
have
been
established
for
grasses
and
livestock
commodities
(40
CFR
§180.390).
These
tolerances
are
expressed
in
terms
of
the
combined
residues
of
N[
5(
1,1
diemthylethyl)
1,3,4
thiadiazol
2
yl]
N,
N'
dimethylurea
and
its
metabolites
containing
the
dimethylethyl
thiadiazole
moiety.
Adequate
enforcement
methods
are
available
for
the
determination
of
residues
in/
on
grasses
and
in
animal
tissues
and
milk.
Tebuthiuron
is
a
List
A
FIFRA
reregistration
chemical
that
was
the
subject
of
a
Reregistration
Standard
Guidance
Document
dated
7/
87.
The
Residue
Chemistry
Chapter
of
the
Tebuthiuron
Tolerance
Reregistration
Eligibility
Decision
(TRED)
is
being
completed
in
conjunction
with
this
document
and
reflects
the
evaluation
of
all
the
submissions
made
in
response
to
the
earlier
reregistration
documents.
No
monitoring
data
were
available
for
tebuthiuron.
An
adequate
method
is
available
for
the
enforcement
of
plant
commodity
tolerances.
A
GLC
with
flame
photometric
detection
is
designated
as
Method
II
in
PAM
Vol.
II.
Tebuthiuron
and
metabolites
104
and
109
are
thermally
degraded
on
the
GLC
column
and
are
determined
as
104;
metabolite
103(
OH)
is
determined
as
104(
OH).
A
revised
enforcement
method
for
milk,
to
include
hydrolysis
steps
and
the
determination
of
metabolites
104(
OH)
and
109(
OH)
is
being
requested.
The
stated
detection
limits
are
0.1
ppm
for
tebuthiuron
and
metabolites
104
and
109,
and
0.2
ppm
for
metabolite
103(
OH).
Residues
in
meat
and
milk
were
estimated
using
livestock
feeding
studies.
The
order
of
preference
for
the
purpose
of
refining
dietary
exposure
assessment
is
usually:
monitoring
data>
field
trial
data>
tolerance.
The
registrant
submitted
all
field
trial
data
for
registered
uses
of
tebuthiuron
on
plant
commodities
which
reflect
maximum
application
rates
and
shortest
PHIs
(S.
Funk,
D187699,
8/
93).
Metabolites
C
For
dietary
risk
assessment,
the
Metabolism
Committee
concluded
that
the
residues
of
concern
in
plants
are
the
parent
compound
and
its
metabolites
103,
103(
OH),
104,
and
109.
The
residues
of
concern
in
livestock
commodities
(fat,
meat,
kidney,
and
liver)
are
tebuthiuron
and
its
metabolites
104,
106,
108,
and
109;
the
terminal
residues
of
concern
in
milk
are
tebuthiuron
and
metabolites
104,
104(
OH),
106,
109,
and
109(
OH).
A
poultry
metabolism
study
is
not
required
since
grasses
are
not
considered
to
be
poultry
feed
items.
DP
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Percent
Crop
Treated
Information
C
An
updated
quantitative
usage
analysis
for
tebuthiuron
was
provided
by
BEAD
based
on
data
years
1996
99
(S.
Smearman,
Biological
and
Economic
Analysis
Division,
2/
28/
02).
The
percentage
of
the
acres
for
each
site
treated
in
1999,
an
average
of
less
than
1
percent
of
rangeland/
pastureland
acreage
was
treated
up
to
an
estimated
maximum
2
percent
of
acres
treated
annually.
For
the
miles
of
railroad
rights
of
way
and
electric
utility
rights
of
way
treated
annually,
the
average
percentage
of
miles
treated
was
less
than
1
percent,
respectively.
No
information
pertaining
to
the
percent
of
area
treated
for
industrial
facilities
or
miles
of
pipeline
rights
of
way
was
available,
but
based
on
the
percentage
of
a.
i.
allocated
to
these
sites
it
is
assumed
that
the
percent
of
area/
mileage
treated
also
averages
less
than
1
percent.
Processing
Information
C
Processing
factors
were
taken
from
the
DEEM
default
values.
Residue
Estimates
for
Meat
and
Milk
C
The
only
source
of
dietary
(food)
exposure
is
the
consumption
of
secondary
residues
in
meat
and
milk
from
livestock
fed
tebuthiuron
treated
grass
forage
and
hay.
Tolerances
in
meat
(2ppm)
and
milk
(0.3
ppm)
are
established
and
in
grass
forage
and
hay
at
10
ppm
for
residues
of
tebuthiuron
and
its
metabolites
containing
the
dimethyl
thiadiazole
moiety.
C
The
residues
of
concern
in
livestock
commodities
(fat,
meat,
kidney,
and
liver)
are
tebuthiuron
and
its
metabolites
104,
106,
108,
and
109;
the
terminal
residues
of
concern
in
milk
are
tebuthiuron
and
metabolites
104,
104(
OH),
106,
109,
and
109(
OH).
A
poultry
metabolism
study
is
not
required
since
grasses
are
not
considered
to
be
poultry
feed
items.
C
Feeding
studies
(S.
Funk,
Ruminant
Feeding
Study,
D217379,
12/
05/
95)
have
demonstrated
a
transfer
of
tebuthiuron
to
animal
tissue
(meat,
meat
by
products,
etc.).
The
results
of
the
ruminant
feeding
study
conducted
at
a
nominal
45
ppm
tebuthiuron
feeding
level
for
28
days
show
that
the
existing
tolerances
for
milk
and
meat
are
inadequate
and
should
be
revised.
The
tolerances
for
meat
(2
ppm)
and
fat
(2
ppm)
may
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be
lowered
to
1
ppm,
but
the
tolerances
for
milk
(0.3
ppm)
and
meat
byproducts
(2
ppm)
must
be
increased
to
0.8
ppm
for
milk
and
5
ppm
for
meat
byproducts.
C
A
dietary
burden
of
tebuthiuron
for
beef
cattle
(extrapolating
to
goats,
sheep
and
horses)
is
based
on
the
feed
items
of
grass
forage.
For
dairy
cattle,
the
residues
used
were
the
average
residues
from
grass
forage
field
trials
while
for
beef
cattle
the
highest
average
field
trial
(HAFT)
residue
values
were
used.
See
Table
2
below.
Table
2:
Dietary
Burden
of
Tebuthiuron
to
Beef
and
Dairy
Cattle
Commodity
%
DM
a
Beef
Cattle
Dairy
Cattle
Average
Field
Trial
Data
(ppm)
b
%
Diet
a
Concentration
(ppm)
HAFT
b
(ppm)
%
Diet
a
Concentration
c
(ppm)
Grass
Forage
25
1.97
60
2.56
2.56
60
6.14
Corn
grain
88
0
40
0
0
40
0
TOTAL
100
2.56
100
6.14
a
OPPTS
Guideline
860.1000
b
Beef
cattle
based
on
average
field
trial
data;
dairy
cattle
based
on
highest
average
field
trial
(HAFT)
data
c
Ruminant
contribution=
[tolerance/
%DM]
x
%diet
Dow
Elanco
dosed
four
groups
of
three
dairy
cows
each
for
28
days
with
gelatin
capsules
containing
tebuthiuron
at
nominal
dosage
rates
of
0
ppm,
45
ppm
(9.5x),
135
ppm
(28.5x),
and
450
ppm
(95x).
Daily
milk
samples
were
collected,
and
within
24
hours
of
the
last
dosing
the
cows
were
sacrificed
and
tissues
were
collected.
For
beef
cattle,
the
nominal
dosage
rates
of
0
ppm,
45
ppm
(7.3x),
135
ppm
(22x),
and
450
ppm
(73x)
were
determined
based
on
the
dietary
burden
for
beef
cattle.
Tissue
samples
(5
grams)
were
analyzed
by
Method
GRM
94.01,
which
determines
tebuthiuron
and
metabolites
104,
106,
108
and
109.
Liver,
kidney,
muscle,
or
fat
was
hydrolyzed
with
6N
HCl
which
converts
metabolite
109
to
104.
The
maximum
incurred
residues
in
various
tissues
at
the
45
ppm
feeding
level,
expressed
as
the
sum
of
tebuthiuron,
104
+
109
as
104,
and
106
+
108
as
106.
Results
of
the
analyses
of
bovine
tissues
are
summarized
in
Table
3.
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Table
3:
Residues
of
Tebuthiuron
and
Metabolites
in
Tissues
from
the
Oral
Administration
of
Tebuthiuron
for
28
Days
Diet
(ppm
tebuthiuron)
Tissue
Analyte
Concentration
1
(ppm)
Range
2
(ppm)
Average
3
(ppm)
0
liver
tebuthiuron
<0.1
4
<0.1
4
104
+
109
5
0.032
<0.05
4
0.039
+
0.010
6
106
+
108
7
0.104
0.368
0.201
+
0.14
kidney
tebuthiuron
0.055
<0.1
4
0.075
+
0.023
104
+
109
5
0.108
<0.2
4
0.138
+
0.054
106
+
108
7
<0.1
4
0.19
0.248
+
0.19
muscle
tebuthiuron
<0.2
4
<0.2
4
104
+
109
5
<0.06
4
<0.06
4
106
+
108
7
<0.06
4
<0.06
4
fat
tebuthiuron
<0.01
4
0.01
4
104
+
109
5
0.006
<0.01
4
0.007
+
0.002
106
+
108
7
<0.01
<0.01
45
liver
tebuthiuron
<0.1
<0.1
104
+
109
5
0.94
2.13
1.73
+
0.68
106
+
108
7
1.50
1.80
1.65
+
0.15
kidney
tebuthiuron
<0.1
<0.1
104
+
109
5
0.355
0.907
0.679
+
0.29
106
+
108
7
0.756
1.06
0.873
+
0.16
muscle
tebuthiuron
<0.2
<0.2
104
+
109
5
0.214
0.560
0.418
+
0.18
106
+
108
7
0.196
0.230
0.216
+
0.018
fat
tebuthiuron
<0.01
<0.01
104
+
109
5
0.12
0.38
0.206
+
0.15
106
+
108
7
0.033
0.164
0.093
+
0.066
135
liver
tebuthiuron
0.098
0.265
0.154
+
0.096
104
+
109
5
4.46
8.23
6.96
+
2.16
106
+
108
7
2.76
3.67
3.35
+
0.51
kidney
tebuthiuron
0.050
0.069
0.059
+
0.01
104
+
109
5
1.58
2.72
2.27
+
0.60
106
+
108
7
1.44
3.20
2.22
+
0.90
muscle
tebuthiuron
0.120
0.140
0.13
+
0.01
104
+
109
5
1.32
2.86
2.26
+
0.82
106
+
108
7
0.466
0.816
0.601
+
0.19
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Table
3:
Residues
of
Tebuthiuron
and
Metabolites
in
Tissues
from
the
Oral
Administration
of
Tebuthiuron
for
28
Days
Diet
(ppm
tebuthiuron)
Tissue
Analyte
Concentration
1
(ppm)
Range
2
(ppm)
Average
3
(ppm)
8
fat
tebuthiuron
0.01
0.074
0.036
+
0.03
104
+
109
5
0.52
2.00
1.33
+
0.75
106
+
108
7
0.158
0.428
0.250
+
0.15
450
liver
tebuthiuron
0.359
1.20
0.666
+
0.46
104
+
109
5
28.4
41.6
33.3
+
7.2
106
+
108
7
11.2
18.0
14.6
+
3.4
kidney
tebuthiuron
0.107
0.244
0.155
+
0.77
104
+
109
5
10.5
15.4
13.5
+
2.1
106
+
108
7
5.79
8.78
6.80
+
1.7
muscle
tebuthiuron
0.210
0.370
0.280
+
0.082
104
+
109
5
8.96
13.6
11.2
+
2.3
106
+108
7
2.68
3.95
3.11
+
0.73
fat
tebuthiuron
0.064
0.140
0.100
+
0.038
104
+
109
5
5.03
6.64
5.61
+
0.89
106
+
108
7
0.830
1.26
1.01
+
0.22
1
Not
corrected
for
concurrent
method
recovery.
2
Range
of
average
of
duplicate
determinations
for
three
cows.
3
Average
of
duplicate
determinations
for
three
cows.
4
"<"
values
are
estimated
limits
of
detection.
5
Results
are
expressed
as
104
equivalents.
6
<0.01
values
were
assigned
0.01.
7
Results
are
expressed
as
106
equivalents.
Milk
samples
were
analyzed
for
residues
of
tebuthiuron
and
metabolites
104,
106,
109,
104(
OH),
and
109(
OH)
using
Method
GRM
92.08.
Metabolites
109
and
109(
OH)
were
converted
to
metabolites
104
and
104(
OH),
respectively,
in
an
initial
acid
hydrolysis.
The
hydrolysis
product
mixture
was
partitioned
with
ethyl
acetate
and
purified
on
a
neutral
alumina
solid
phase
extraction
cartridge.
A
separate
sample
was
required
for
metabolite
106.
The
maximum
incurred
residue
in
milk
at
the
45
ppm
feeding
level,
expressed
as
the
sum
of
tebuthiuron,
104
plus
109
as
104,
104(
OH)
plus
109(
OH)
as
104(
OH),
and
106.
See
Table
4.
Table
4:
Residues
of
Tebuthiuron
and
Metabolites
in
Milk
Diet
(ppm)
Day
1
Analyte
Concentration
2
(ppm)
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0
25
Tebuthiuron
<0.04
3
28
104
+
109
<0.02
28
104(
OH)
+
109(
OH)
<0.01
28
106
<0.01
45
6
12
4
Tebuthiuron
0.017;
0.023
(<
0.14)
5
104
+
109
0.550;
0.726
22
104(
OH)
+
109(
OH)
0.063;
0.116
5
106
0.118;
0.132
135
7
22
Tebuthiuron
5
0.227;
0.480
5
104
+
109
3.03;
3.38
22
104(
OH)
+
109(
OH)
0.143;
0.188
5
106
0.507;
0.626
450
8
22
Tebuthiuron
1.47;
3.18
25
104
+
109
23.0;
40.8
22
104(
OH)
+
109(
OH)
1.15;
1.64
28
9
106
4.13;
5.25
1
Day
of
plateau
of
residue,
unless
otherwise
indicated.
2
Not
corrected
for
concurrent
method
recovery.
First
entry
is
average
of
three
cows;
second
entry
is
maximum
residue.
For
104
+
109,
results
are
expressed
as
104
equivalents.
For
104(
OH)
+
109(
OH),
results
are
expressed
as
104(
OH)
equivalents.
3
"<"
values
are
estimated
limits
of
detection.
4
Residues
were
lower
on
subsequent
days,
except
one
cow
(0.035
ppm)
on
day
13.
5
Results
were
variable
among
cows
on
a
given
days
and
among
different
days.
The
residue
ranged
from
0.148
to
0.288
ppm
on
day
25,
0.205
ppm
average,
112%
recovery.
6
Actual
feeding
levels
were
71,
51,
and
56
ppm.
7
Actual
feeding
levels
were
192,
197,
and
136
ppm.
8
Actual
feeding
levels
were
903,
587,
and
646
ppm.
9
Residue
may
not
have
plateaued,
but
low
recovery
(40%)
obscures
trends.
The
average
residues
in
various
tissues
at
the
45
ppm
(7.3x),
135
ppm
(22x),
and
450
ppm
(73x)
feeding
levels,
expressed
as
the
sum
of
tebuthiuron,
104
+
109,
and
106
+
108;
and
the
total
residues
at
6.14
ppm
tebuthiuron,
assuming
a
linear
regression
relationship
between
diet
intake
and
residues,
are
summarized
in
Table
5a.
Table
5a:
Average
Residues
for
Each
Tissue
Based
on
Linear
Regression
Beef
Cattle
Diet
(ppm)
Liver
(ppm)
Muscle
(ppm)
Kidney
(ppm)
Fat
(ppm)
45ppm
(7.3x)
3.43
0.80
1.6
0.
31
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10
135ppm
(22x)
10.44
2.96
4.53
1.62
450ppm
(73x)
48.57
14.55
19.79
6.72
Calculated
Maximum
at
6.14
ppm
(1x)
0.646
0.193
0.264
0.090
For
milk,
the
average
residues
in
milk
at
the
45
ppm
(9.5x),
135
ppm
(28.5x),
and
450
ppm
(95x)
feeding
levels,
expressed
as
the
sum
of
tebuthiuron,
104
+
109,
and
104(
OH)
+
109(
OH),
and
106;
and
the
total
residues
at
4.73
ppm
tebuthiuron,
assuming
a
linear
regression
relationship
between
diet
intake
and
residues,
are
summarized
in
Table
5b.
Table
5b:
Average
Residues
for
Milk
Based
on
Linear
Regression
Dairy
Cattle
Diet
(ppm)
Milk
(ppm)
45ppm
(9.5x)
0.748
135ppm
(28.5x)
3.91
450ppm
(95x)
29.75
Calculated
Maximum
at
4.73
ppm
(1x)
0.296
Example:
Calculation
for
Liver
Step
1:
The
sum
of
the
average
of
tebuthiuron
residues,
average
104
+
109
residues,
and
106
+
108
residues
are
calculated
from
the
feeding
studies
(see
Table
4).
Average
refers
to
the
average
of
duplicate
analyses
per
each
of
the
three
cows.
Please
note
the
values
using
½
LOD.
45
ppm:
0.05
ppm
(parent)
+
1.73
ppm
(104
+
109)
+
1.65
ppm
(106
+
108)=
3.43
135
ppm:
0.129
ppm
(parent)
+
6.96
ppm
(104
+
109)
+
3.35
ppm
(106
+
108)=
10.44
450
ppm:
0.668
ppm
(parent)
+
33.25
ppm
(104
+
109)
+
14.65
ppm
(106
+
108)=
48.57
Step
2:
The
linear
relationship
(average
residues
versus
beef
cattle
diets)
for
liver
was
derived
from
Table
5a
using
linear
regression
graph
and
equation
to
determine
1x.
Table
6.
Summary
of
Tebuthiuron
and
its
Metabolites
in
Meat
and
Milk
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RAC
Anticipated
Residues
Chronic
(ppm)
Acute
(RDF)
Liver
0.
006
(0.646
ppm
x
1%
CT)
0.013
(0.646
ppm
x
2%
CT)
Kidney
0.
003
(0.264
ppm
x
1%
CT)
0.005
(0.264
ppm
x
2%
CT)
Muscle
0.002
(0.193
ppm
x
1%
CT)
0.004
(0.193
ppm
x
2%
CT)
Fat
0.
001
(0.090
ppm
x
1%
CT)
0.002
(0.090
ppm
x
2%
CT)
Milk
0.003
(0.296
ppm
x
1%
CT)
0.006
(0.296
ppm
x
2%
CT)
I.
DEEM™
Program
and
Consumption
Information
Tebuthiuron
acute
and
chronic
dietary
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(DEEM™)
software
Version
7.74,
which
incorporates
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intake
by
Individuals
(CSFII),
1989
1992.
The
1989
92
data
are
based
on
the
reported
consumption
of
more
than
10,000
individuals
over
three
consecutive
days,
and
therefore
represent
more
than
30,000
unique
"person
days"
of
data.
Foods
"as
consumed"
(e.
g.,
apple
pie)
are
linked
to
raw
agricultural
commodities
and
their
food
forms
(e.
g.,
apples
cooked/
canned
or
wheat
flour)
by
recipe
translation
files
internal
to
the
DEEM
software.
Consumption
data
are
averaged
for
the
entire
US
population
and
within
population
subgroups
for
chronic
exposure
assessment,
but
are
retained
as
individual
consumption
events
for
acute
exposure
assessment.
For
chronic
exposure
and
risk
assessment,
an
estimate
of
the
residue
level
in
each
food
or
food
form
(e.
g.,
orange
or
orange
juice)
on
the
commodity
residue
list
is
multiplied
by
the
average
daily
consumption
estimate
for
that
food/
food
form.
The
resulting
residue
consumption
estimate
for
each
food/
food
form
is
summed
with
the
residue
consumption
estimates
for
all
other
food/
food
forms
on
the
commodity
residue
list
to
arrive
at
the
total
estimated
exposure.
Exposure
estimates
are
expressed
in
mg/
kg
body
weight/
day
and
as
a
percent
of
the
cPAD.
This
procedure
is
performed
for
each
population
subgroup.
DP
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12
For
acute
exposure
assessments,
individual
one
day
food
consumption
data
are
used
on
an
individual
by
individual
basis.
The
reported
consumption
amounts
of
each
food
item
can
be
multiplied
by
a
residue
point
estimate
and
summed
to
obtain
a
total
daily
pesticide
exposure
for
a
deterministic
(Tier
1
or
Tier
2)
exposure
assessment,
or
"matched"
in
multiple
random
pairings
with
residue
values
and
then
summed
in
a
probabilistic
(Tier
3/
4)
assessment.
The
resulting
distribution
of
exposures
is
expressed
as
a
percentage
of
the
aPAD
on
both
a
user
(i.
e.,
those
who
reported
eating
relevant
commodities/
food
forms)
and
a
per
capita
(i.
e.,
those
who
reported
eating
the
relevant
commodities
as
well
as
those
who
did
not)
basis.
In
accordance
with
HED
policy,
per
capita
exposure
and
risk
are
reported
for
all
tiers
of
analysis.
However,
for
tiers
1
and
2,
significant
differences
in
user
vs.
per
capita
exposure
and
risk
are
identified
and
noted
in
the
risk
assessment.
II.
Results/
Conclusions
Acute
Dietary
Exposure
Analysis
A
Tier
2
acute
and
chronic
dietary
risk
assessments
were
conducted
for
all
supported
tebuthiuron
food
uses.
Dietary
risk
estimates
are
provided
for
the
general
U.
S.
population
(chronic
only)
and
females
13
50
years
(acute).
This
assessment
concludes
that
for
all
included
commodities,
the
acute
risk
estimates
are
below
the
Agency's
level
of
concern
(<
100%
aPAD)
at
the
95
th
exposure
percentile
for
females
13
50
years
(<
1%
of
the
aPAD).
This
assessment
also
concludes
that
for
all
commodities,
the
chronic
risk
estimates
are
below
the
Agency's
level
of
concern
(<
100%
cPAD)
for
the
general
U.
S.
population
(<
1%
of
the
cPAD)
and
all
population
subgroups.
The
results
reported
in
Table
7
are
for
females
13
50
years
only
for
acute
dietary
exposure
analysis
and
Table
8
is
the
results
of
chronic
dietary
exposure
analysis.
Table
7.
Results
of
Acute
Dietary
Exposure
Analysis
Population
Subgroup
95
th
Percentile
99
th
Percentile
99.9
th
Percentile
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
aPAD
Females
13
50
years
old
0.000078
<1
0.000121
<1
0.000207
<1
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Chronic
Dietary
Exposure
Analysis
Table
8.
Results
of
Chronic
Dietary
Exposure
Analysis
Population
Subgroup
Exposure
(mg/
kg/
day)
%
cPAD
U.
S.
Population
(total)
0.000023
<1
All
Infants
(<
1
year)
0.
000036
<1
Children
1
6
years
0.
000083
<1
Children
7
12
years
0.
000043
<1
Females
13
50
0.000013
<1
Males
13
19
0.000025
<1
Males
20+
years
0.
000012
<1
Seniors
55+
0.000012
<1
III.
Discussion
of
Uncertainties
C
Residue
Issues
The
Agency
notes
that
field
trial
data
are
generally
considered
by
HED
as
an
upper
end
or
a
worst
case
scenario
of
possible
residues
and
are
more
suited
to
the
requirements
of
tolerance
setting,
because
it
requires
the
highest
rates
of
application
and
shortest
PHI,
than
to
the
requirements
of
dietary
exposure
assessment
(when
the
most
realistic
estimate
is
desired).
IV.
List
of
Attachments
Attachment
1:
Acute
Residue
Input
Data
for
DEEM
Analysis
for
Tebuthiuron
Attachment
2:
Acute
Residue
Analysis
for
Tebuthiuron
Attachment
3:
Chronic
Residue
Input
Data
for
DEEM
Analysis
for
Tebuthiuron
Attachment
4:
Chronic
Residue
Analysis
for
Tebuthiuron
DP
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cc:
S.
Piper
(CEB),
RF
RDI:
ChemSAC:
3/
27/
02;
Secondary
Reviewers:
4/
1/
02;
FBSuhre
4/
8/
02
7509C:
CEB:
CM
2:
RM
810F:
308
2717:
Tebuthiuron
Attachment
1:
Acute
Residue
Input
Data
for
DEEM
Analysis
for
Tebuthiuron
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
Acute
analysis
for
TEBUTHIURON
Residue
file
name:
C:\
deem\
tebuthiruon\
tebuthiuronacute.
RS7
Analysis
Date
04
02
2002
Residue
file
dated:
04
02
2002/
15:
58:
50/
8
Reference
dose:
aRfD
=
0.083
mg/
kg
bw/
day
NOEL
=
25
mg/
kg
bw/
day
Comment:
Assumes
3x
factor
for
FQPA
females
13
50
yrs
only
Food
Crop
Food
Name
Def
Res
Adj.
Factors
RDL
Code
Grp
(ppm)
#1
#2
Ind
318
D
Milk
nonfat
solids
0.296000
1.000
0.020
319
D
Milk
fat
solids
0.296000
1.000
0.020
320
D
Milk
sugar
(lactose)
0.296000
1.000
0.020
321
M
Beef
meat
byproducts
0.646000
1.000
0.020
322
M
Beef
other
organ
meats
0.646000
1.000
0.020
323
M
Beef
dried
0.193000
1.920
0.020
324
M
Beef
fat
w/
o
bones
0.090000
1.000
0.020
325
M
Beef
kidney
0.264000
1.000
0.020
326
M
Beef
liver
0.646000
1.000
0.020
327
M
Beef
lean
(fat/
free)
w/
o
bones
0.193000
1.000
0.020
328
M
Goat
meat
byproducts
0.646000
1.000
0.020
329
M
Goat
other
organ
meats
0.646000
1.000
0.020
330
M
Goat
fat
w/
o
bone
0.090000
1.000
0.020
331
M
Goat
kidney
0.264000
1.000
0.020
332
M
Goat
liver
0.646000
1.000
0.020
333
M
Goat
lean
(fat/
free)
w/
o
bone
0.193000
1.000
0.020
334
M
Horsemeat
0.193000
1.000
0.020
336
M
Sheep
meat
byproducts
0.646000
1.000
0.020
337
M
Sheep
other
organ
meats
0.646000
1.000
0.020
338
M
Sheep
fat
w/
o
bone
0.090000
1.000
0.020
339
M
Sheep
kidney
0.264000
1.000
0.020
340
M
Sheep
liver
0.646000
1.000
0.020
341
M
Sheep
lean
(fat
free)
w/
o
bone
0.193000
1.000
0.020
398
D
Milk
based
water
0.296000
1.000
0.020
Attachment
2:
Acute
Residue
Analysis
for
Tebuthiuron
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
ACUTE
Analysis
for
TEBUTHIURON
(1989
92
data)
Residue
file:
tebuthiuronacute.
RS7
Adjustment
factor
#2
used.
Analysis
Date:
04
02
2002/
15:
54:
34
Residue
file
dated:
04
02
2002/
15:
51:
52/
8
NOEL
(Acute)
=
25.000000
mg/
kg
body
wt/
day
Daily
totals
for
food
and
foodform
consumption
used.
Run
Comment:
"Assumes
3x
factor
for
FQPA
females
13
50
yrs"
===============================================================================
DP
Barcode:
D281821
Dietary
exposure
assessment
/
15
Tebuthiuron
/
105501
15
Summary
calculations
(per
capita):
95th
Percentile
99th
Percentile
99.9th
Percentile
Exposure
%
aRfD
MOE
Exposure
%
aRfD
MOE
Exposure
%
aRfD
MOE
Females
13+
(preg/
not
nursing):
0.000109
0.13
229030
0.000128
0.15
195001
0.000195
0.24
128105
Females
13+
(nursing):
0.000118
0.14
211948
0.000183
0.22
136354
0.000195
0.23
128528
Females
13
19
(not
preg
or
nursing):
0.000098
0.12
255390
0.000175
0.21
142798
0.000235
0.28
106564
Females
13
50
yrs:
0.000078
0.09
319551
0.000121
0.15
206558
0.000207
0.25
120907
Attachment
3:
Chronic
Residue
Input
Data
for
DEEM
Analysis
for
Tebuthiuron
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
Chronic
analysis
for
TEBUTHIURON
1989
92
data
Residue
file:
C:\
deem\
tebuthiruon\
tebuthirchronic.
RS7
Adjust.
#2
used
Analysis
Date
04
02
2002
Residue
file
dated:
04
02
2002/
15:
52:
42/
8
Reference
dose
(RfD)
=
0.14
mg/
kg
bw/
day
Comment:
Assumes
1x
factor
for
FQPA
Food
Crop
RESIDUE
Adj.
Factors
Code
Grp
Food
Name
(ppm)
#1
#2
318
D
Milk
nonfat
solids
0.296000
1.000
0.010
319
D
Milk
fat
solids
0.296000
1.000
0.010
320
D
Milk
sugar
(lactose)
0.296000
1.000
0.010
321
M
Beef
meat
byproducts
0.646000
1.000
0.010
322
M
Beef
other
organ
meats
0.646000
1.000
0.010
323
M
Beef
dried
0.193000
1.920
0.010
324
M
Beef
fat
w/
o
bones
0.090000
1.000
0.010
325
M
Beef
kidney
0.264000
1.000
0.010
326
M
Beef
liver
0.646000
1.000
0.010
327
M
Beef
lean
(fat/
free)
w/
o
bones
0.193000
1.000
0.010
328
M
Goat
meat
byproducts
0.646000
1.000
0.010
329
M
Goat
other
organ
meats
0.646000
1.000
0.010
330
M
Goat
fat
w/
o
bone
0.090000
1.000
0.010
331
M
Goat
kidney
0.264000
1.000
0.010
332
M
Goat
liver
0.646000
1.000
0.010
333
M
Goat
lean
(fat/
free)
w/
o
bone
0.193000
1.000
0.010
334
M
Horsemeat
0.193000
1.000
0.010
336
M
Sheep
meat
byproducts
0.646000
1.000
0.010
337
M
Sheep
other
organ
meats
0.646000
1.000
0.010
338
M
Sheep
fat
w/
o
bone
0.090000
1.000
0.010
339
M
Sheep
kidney
0.264000
1.000
0.010
340
M
Sheep
liver
0.646000
1.000
0.010
341
M
Sheep
lean
(fat
free)
w/
o
bone
0.193000
1.000
0.010
398
D
Milk
based
water
0.296000
1.000
0.010
DP
Barcode:
D281821
Dietary
exposure
assessment
/
16
Tebuthiuron
/
105501
16
Attachment
4:
Chronic
Residue
Analysis
for
Tebuthiuron
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
Chronic
analysis
for
TEBUTHIURON
(1989
92
data)
Residue
file
name:
C:\
deem\
tebuthiruon\
tebuthirchronic.
RS7
Adjustment
factor
#2
used.
Analysis
Date
04
02
2002/
16:
03:
16
Residue
file
dated:
04
02
2002/
15:
52:
42/
8
Reference
dose
(RfD,
Chronic)
=
.14
mg/
kg
bw/
day
COMMENT
1:
Assumes
1x
factor
for
FQPA
===============================================================================
Total
exposure
by
population
subgroup
Total
Exposure
Population
mg/
kg
Percent
of
Subgroup
body
wt/
day
Rfd
U.
S.
Population
(total)
0.000023
0.0%
U.
S.
Population
(spring
season)
0.000023
0.0%
U.
S.
Population
(summer
season)
0.000022
0.0%
U.
S.
Population
(autumn
season)
0.000024
0.0%
U.
S.
Population
(winter
season)
0.000023
0.0%
Northeast
region
0.000023
0.0%
Midwest
region
0.000026
0.0%
Southern
region
0.000021
0.0%
Western
region
0.000023
0.0%
Hispanics
0.000025
0.0%
Non
hispanic
whites
0.000023
0.0%
Non
hispanic
blacks
0.000020
0.0%
Non
hisp/
non
white/
non
black
0.000024
0.0%
All
infants
(<
1
year)
0.000036
0.0%
Nursing
infants
0.000007
0.0%
Non
nursing
infants
0.000048
0.0%
Children
1
6
yrs
0.000083
0.1%
Children
7
12
yrs
0.000043
0.0%
Females
13
19
(not
preg
or
nursing)
0.000019
0.0%
Females
20+
(not
preg
or
nursing)
0.000011
0.0%
Females
13
50
yrs
0.000013
0.0%
Females
13+
(preg/
not
nursing)
0.000022
0.0%
Females
13+
(nursing)
0.000019
0.0%
Males
13
19
yrs
0.000025
0.0%
Males
20+
yrs
0.000012
0.0%
Seniors
55+
0.000012
0.0%
Pacific
Region
0.000023
0.0%
| epa | 2024-06-07T20:31:42.630689 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0146-0006/content.txt"
} |
EPA-HQ-OPP-2002-0146-0007 | Supporting & Related Material | "2002-08-29T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
April
9,
2002
SUBJECT:
Tebuthiuron
Residue
Chemistry
Chapter
for
the
Tolerance
Reassessment
Eligibility
Decision
(TRED);
PC
codes
105501;
DP
Barcode
D277103.
FROM:
Sheila
Piper,
Chemist
Chemistry
and
Exposure
Branch
Health
Effects
Division
(7509C)
THROUGH:
F.
B.
Suhre,
Branch
Senior
Scientist
Chemistry
and
Exposure
Branch
Health
Effects
Division
(7509C)
TO:
Paula
Deschamp,
Risk
Assessor
Reregistration
Branch
II
Health
Effects
Division
(7509C)
and
Wilhelmena
Livingston,
Chemical
Review
Manager
Special
Review
Branch
Special
Review
and
Reregistration
Division
(7508C)
The
Tolerance
Reassessment
Eligibility
Document
(TRED)
for
tebuthiuron
has
undergone
secondary
review
in
the
branch
and
has
been
revised
to
reflect
Agency
policies.
cc:
S.
Piper
(CEB),
RF
RDI:
ChemSAC:
3/
27/
02:
Secondary
Reviewers:
3/
27/
02:
F.
B.
Suhre
4/
8/
02
7509C:
CEB:
CM
2:
RM
810F:
308
2717:
Tebuthiuron
2
N
N
S
N
CH
3
CH
3
C
H
3
C
H
3
O
N
H
CH
3
TEBUTHIURON
INTRODUCTION
Tebuthiuron
[N[
5(
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N,
N'
dimethylurea]
is
a
relatively
nonselective,
soil
activated
herbicide
registered
for
use
to
control
broadleaf,
woody
weeds,
grasses,
and
brush
on
terrestrial
feed
crop
sites
(pastures
and
rangeland)
primarily
in
TX,
OK,
and
NM.
Tebuthiuron
is
also
used
on
terrestrial
non
food
crop
such
as
airports/
landing
fields,
industrial
areas,
non
agricultural
rights
of
way,
fencerows,
hedgerows,
and
non
agricultural
uncultivated
areas/
soil;
there
is
no
agricultural
crop
use
of
tebuthiuron
except
for
range
and
pasture
land
uses.
Pelleted/
tablets
(P/
T)
is
the
only
tebuthiuron
formulation
class
registered
for
use
on
food/
feed
crops.
The
registered
mode
of
application
is
broadcast
using
ground
or
aerial
equipment
(Source:
LUIS
General
Chemical
Report
for
Tebuthiuron,
5/
20/
92).
There
are
no
registered
residential
uses.
GLN
860.1000:
REGULATORY
BACKGROUND
Tolerances
for
residues
of
tebuthiuron
have
been
established
for
grasses
and
animal
commodities
[40
CFR
§180.390].
These
tolerances
are
expressed
in
terms
of
the
combined
residues
of
N[
5
(1,
1diemethylethyl)
1,
3,
4
thiadiazol
2
yl]
N,
N'
dimethylurea
and
its
metabolites
containing
the
dimethylethyl
thiadiazole
moiety.
Adequate
enforcement
methods
are
available
for
the
determination
of
residues
in/
on
grasses
and
in
animal
tissues
and
milk.
Tebuthiuron
was
first
registered
by
Elanco
Products
Company
in
1974.
The
registration
was
later
transferred
to
DowElanco
(currently
Dow
AgroSciences
LLC)
in
1989.
The
Tebuthiuron
Reregistration
Standard
Guidance
Document
was
issued
7/
87
for
all
pesticide
products
containing
the
active
ingredient,
tebuthiuron.
The
information
contained
in
this
document
outlines
the
Residue
Chemistry
Science
Assessments
with
respect
to
the
reregistration
of
tebuthiuron.
The
summaries
of
residue
chemistry
guidelines
and
topics
listed
below
are
based
on
the
present
regulatory
status
where
the
only
registered
food/
feed
use
of
tebuthiuron
is
on
grasses
grown
in
pasture
and
rangeland.
The
Agency
reserves
the
right
to
require
additional
studies
for
each
applicable
residue
chemistry
guideline
and
topic
if
additional
registrations
on
food/
feed
crops
other
than
pasture
and
rangeland
grasses
are
sought,
or
if
a
tolerance
change
is
proposed.
3
N
N
S
N
CH
3
CH
3
C
H
3
O
N
H
CH
3
OH
N
N
S
NH
2
CH
3
C
H
3
C
H
3
N
N
S
N
CH
3
CH
3
C
H
3
C
H
3
O
NH
2
N
N
S
N
CH
3
CH
3
C
H
3
C
H
3
O
N
H
OH
N
N
S
N
CH
3
CH
3
C
H
3
O
NH
2
OH
N
N
S
N
CH
3
CH
3
C
H
3
O
N
H
OH
OH
N
N
S
N
H
CH
3
C
H
3
C
H
3
O
NH
2
Figure
A.
The
chemical
structures
of
the
metabolites
of
concern
of
tebuthiuron
Structure
Metabolite:
Chemical
name
Structure
Metabolite:
Chemical
name
103
(OH):
N[
5(
2
hydroxy
1,1
dimethylethyl)
1,3,
4
thiadiazol
2
yl]
N,
N'
dimethylurea
108:
2
dimethylethyl
5
amino
1,
3,
4
thiadiazole
104:
N[
5(
1,1
dimethylethyl)
1,3,
4
thiadiazol
2
yl
N
methylurea
109:
N[
5(
1,1
dimethylethyl)
1,3,
4
thiadiazol
2
yl
N'
hydroxymethyl
N
methylurea
104
(OH):
N[
5(
2
hydroxy
1,1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N
methylurea
A
[109
(OH)]:
N[
5(
2
hydroxy
1,1
dimethylethyl
1,3,4
thiadiazol
2
yl]
N'
hydroxymethyl
N
methylurea
106:
N[
5(
1,1
dimethylethyl)
1,3,
4
thiadiazol
2
yl]
urea
4
SUMMARY
OF
SCIENCE
FINDINGS
GLN
860.1200:
Directions
for
Use
Based
on
a
search
of
OPP's
REFs
conducted
on
March
22,
2002,
there
are
eight
active
Section
3
registrations
for
end
use
products
containing
tebuthiuron.
End
use
formulations
include
granular,
pelleted/
tablets,
and
wettable
powder
products
which
are
applied
using
ground
and
aerial
equipment.
A
summary
of
the
currently
registered
end
use
products
and
use
sites
is
given
in
the
Table
1
below:
Table
1:
Current
registered
end
use
products
and
use
sites
Company
EPA
Reg.
No.
Formulation
Class
%
ai
Use
Sites
Rainbow
Technology
Corp
13283
18
Granular
2
Industrial
areas
(outdoor)
Non
agricultural
rights
of
way/
fencerows/
hedgerows
13283
21
Granular
1
Industrial
areas
(outdoor)
Non
agricultural
rights
of
way/
fencerows/
hedgerows
SSI
Maxim
Company,
Inc.
34913
10
Granular
5
Drainage
systems
Non
agricultural
uncultivated
areas/
soils
34913
15
Granular
1
Non
agricultural
uncultivated
areas/
soils
34913
16
Granular
2
Non
agricultural
uncultivated
areas/
soils
Dow
AgroSciences
LLC
62719
107
Wettable
Powder
80
Drainage
systems
Non
agricultural
uncultivated
areas/
soils
62719
121
Pelleted/
Tableted
20
Pasture/
rangeland
Non
agricultural
uncultivated
areas/
soils
62719
122
Pelleted/
Tableted
40
Pasture/
rangeland
Non
agricultural
uncultivated
areas/
soils
The
20%
and
40%
P/
T
formulations
(EPA
Reg.
Nos.
62719
121
and
62719
122,
dated
2/
96)
are
registered
for
a
single
broadcast
application
to
rangeland
and
forage
grasses
by
aerial
or
ground
equipment
at
0.
5
4.
00
lb
ai/
A.
Tebuthiuron
may
be
applied
anytime
but
the
recommended
timing
of
application
is
prior
to
the
resumption
of
active
seasonal
growth
in
the
spring
or
before
expected
seasonal
rainfall.
The
maximum
recommended
rate
is
4.0
lb
ai/
A
for
areas
receiving
>20
inches
average
annual
rainfall,
or
2.0
lb
ai/
A
for
areas
receiving
<20
inches
average
annual
rainfall.
Application
to
ditches
used
to
transport
irrigation
or
potable
water
is
prohibited.
1
MARC
members
(C.
Olinger,
L.
Cheng,
R.
Loranger
and
D.
Nixon)
determined
the
residues
of
concern
in
the
tolerance
expression
should
also
be
included
in
the
risk
assessment.
5
GLN
860.1300:
Nature
of
the
Residue
Plants
The
qualitative
nature
of
the
residue
in
grasses
is
adequately
understood.
The
registrant
(1976;
MRID
00020756)
submitted
a
"revised"
metabolism
study
in
which
a
[
14
C]
tebuthiuron
solution
(labeled
in
the
5
position
of
the
thiadiazole
ring;
specific
activity
of
16.
9
uCi/
mg)
was
applied
to
the
surface
of
the
soil
in
which
10
week
old
tall
fescue
(0.374
lb
ai/
A),
little
bluestem
and
indiangrass
(0.75
lb
ai/
A.)
were
grown.
The
residues
of
concern
are
the
parent
compound
and
its
metabolites
103
(OH),
104,
and
109
(N.
Dodd,
MRIDs
40985001
02,
6/
22/
89).
MARC
1
revisited
N.
Dodd's
memo,
"Nature
of
the
Residue
in
Milk
and
Bovine
Tissues,"
dated
6/
22/
89
and
determined
the
parent
compound
and
its
metabolites
103
(OH),
104,
and
109
should
also
be
included
in
the
risk
assessment
(3/
28/
02).
Tebuthiuron
was
the
most
abundant
14
C
residue
recovered
in
the
organosoluble
fraction
of
the
grass
extract.
Other
metabolites
identified
in
the
organosoluble
fraction
from
all
three
grass
species
were
103(
OH),
104,
and
109.
Approximately
39
86%
of
the
total
14
C
activity
of
all
grasses
was
identified
from
the
organosoluble
fraction.
The
metabolites
which
were
recovered
and
identified
following
acid
hydrolysis
of
the
aqueous
fraction
were
103(
OH),
104,
and
l04(
OH).
The
predominant
conjugate
in
little
bluestem
was
103(
OH)
while
104
was
the
major
conjugate
in
indiangrass.
One
additional
metabolite,
isopropyl
103,
was
found
in
the
hydrolysates
of
the
aqueous
fraction
of
little
bluestem.
Based
on
the
14
C
residues
identified
in
the
organosoluble
and
aqueous
fractions,
approximately
81
89,
58
70,
and
78
80%
of
the
total
14
C
activity
found
in
tall
fescue,
little
bluestem,
and
indiangrass,
respectively,
was
identified.
In
summary,
two
major
metabolic
pathways
are
involved:
N
demethylation
of
tebuthiuron
to
form
104
and
alkyl
hydroxylation
of
the
dimethylethyl
side
chain
to
form
103(
OH).
The
molecular
structures
of
the
metabolites
of
concern
are
presented
in
Figure
A.
GLN
860.1300:
Nature
of
the
Residue
Livestock
The
qualitative
nature
of
the
residue
in
milk
and
ruminant
tissues
is
adequately
understood.
The
terminal
residues
of
concern
in
fat,
meat,
kidney,
and
liver
are
tebuthiuron
and
its
metabolites
104,
106,
108,
and
109;
the
terminal
residues
of
concern
in
milk
are
tebuthiuron
and
metabolites
104,
104
(OH),
106,
109,
and
A
[109
(OH)]
for
the
tolerance
expression
and
risk
assessment
(N.
Dodd,
MRIDs
409850
02,
6/
22/
89).
A
poultry
metabolism
study
is
not
required
since
grasses
are
not
considered
to
be
poultry
feed
items.
A
metabolism
study
was
conducted
on
one
cow
in
the
study
titled
"Nature
of
[
14
C]
Tebuthiuron
Residues
in
Bovine
Tissue"
(J.
D.
Magnussen
and
D.
P.
Rainey,
Ph.
D.,
Experiment
ABC0413,
Lilly
Research
Laboratories,
January
24,
1989,
MRID
No.
409850
02).
Capsules
containing
[
14
C]
tebuthiuron
labeled
in
the
5
position
of
the
thiadiazole
ring
were
placed
directly
into
the
rumen
via
a
surgically
fitted
fistula.
The
280
kg
(approximately)
cow
was
given
one
capsule
every
6
12
hours
(morning
and
evening)
for
3
consecutive
days.
Each
capsule
contained
140
mg
[
14
C]
tebuthiuron,
which
the
petitioner
has
calculated
to
be
a
feeding
rate
of
50
ppm.
The
cow
was
sacrificed
12
hours
after
the
final
dose.
The
percentage
of
the
total
radioactivity
which
was
identified
was
82.7
percent
in
fat,
87.2
percent
in
lean,
83.2
percent
in
liver,
and
91.0
percent
in
kidney.
Of
the
total
radioactivity
in
milk,
64.
2
to
68.
1
percent
was
not
conjugated
(i.
e.,
extractable
in
acetonitrile
or
ethyl
acetate).
Between
25.4
and
29.6
percent
were
conjugated
(i.
e.,
polar).
Most
of
the
conjugated
residues
were
released
by
enzyme
or
acid
hydrolysis.
Residues
in
milk
(days
1,
2,
and
3)
as
a
percentage
of
total
radioactivity
were
reported
as
follows:
1.
1
to
1.
2
percent,
parent
(103);
20.7
to
21.6
percent,
104;
21.0
to
26.3
percent,
106;
10.0
to
11.8
percent,
109;
2.2
to
3.
2
percent,
108;
1.0
to
1.
7
percent,
103(
OH);
9.
6
to
16.3
percent,
104(
OH);
7.
6
to
11.8
percent,
Metabolite
A
or
109(
OH);
1.
5
to
7.2
percent,
Metabolite
B;
1.
7
to
2.5
percent,
Metabolite
C;
and
3.
3
to
5.
5
percent,
other.
The
molecular
structures
of
the
metabolites
of
concern
are
presented
in
Figure
A.
GLN
860.1340:
Residue
Analytical
Methods
Plants
and
Livestock
An
adequate
method
is
available
for
the
enforcement
of
plant
commodity
tolerances.
A
GLC
method
with
flame
photometric
detection
is
designated
as
Method
II
in
PAM
Vol.
II.
Tebuthiuron
and
metabolites
104
and
109
are
thermally
degraded
on
the
GLC
column
and
are
determined
as
5(
1,
1
dimethylethyl)
N
methyl
1,
3,
4
thiadiazol
2
amine;
metabolite
103
(OH)
is
determined
as
5(
2
hydroxy
1,
1
dimethylethyl)
N
methyl
1,
3,
4
thiadiazol
2
amine.
The
stated
detection
limits
are
0.
1
ppm
for
tebuthiuron
and
metabolites
104
and
109,
and
0.
2
ppm
for
metabolite
103
(OH).
A
revised
enforcement
method
for
milk,
to
include
hydrolysis
steps
and
the
determination
of
metabolites
104
(OH)
and
A
[109
(OH)],
and
a
revised
enforcement
method
for
animal
tissues,
to
include
hydrolysis
steps
and
the
determination
of
metabolite
108,
were
submitted.
GLN
860.1380:
Storage
Stability
The
available
storage
stability
data
indicate
that
residues
of
tebuthiuron
and
its
metabolites
containing
the
thiadiazole
moiety
[103
(OH),
104,
and
109]
are
stable
for
up
to
ca.
29
months
of
frozen
storage
at
20
C
in/
on
grass
forage
and
hay.
Tebuthiuron
and
its
metabolites
104,
104(
OH),
109,
109(
OH),
and
106
are
stable
in
milk
stored
frozen
for
up
to
6
months.
These
data
are
translated
to
meat
and
stability
data
for
metabolite
108
(not
found
in
milk)
will
not
be
required.
The
stability
data
fully
support
the
ruminant
feeding
study
and
no
additional
data
are
required
(S.
Funk,
D223089,
11/
22/
95).
7
GLN
860.1400:
Water,
Fish
and
Irrigated
Crops
Tebuthiuron
is
presently
not
registered
for
direct
use
on
potable
water
and
aquatic
food
and
feed
crops;
therefore,
no
residue
chemistry
data
are
required
under
these
guideline
topics.
GLN
860.1460:
Food
Handling
Tebuthiuron
is
presently
not
registered
for
use
in
food
handling
establishments;
therefore,
no
residue
chemistry
data
are
required
under
these
guideline
topics.
GLN
860.1480:
Magnitude
of
the
Residue
in
Meat,
Milk,
Poultry
and
Eggs
The
reregistration
requirements
for
data
depicting
magnitude
of
the
residue
in
milk,
eggs,
and
livestock
tissues
are
fulfilled.
The
registrant
submitted
animal
feeding
study
to
reassess
the
adequacy
of
established
tebuthiuron
tolerances
on
animal
commodities.
A
summary
of
the
animal
feeding
data
relative
to
the
maximum
theoretical
dietary
burden
of
tebuthiuron
to
beef
cattle
and
dairy
cattle
are
included
in
this
document.
Maximum
Theoretical
Dietary
Burden
An
acceptable
ruminant
feeding
study
(S.
Funk,
D217379,
12/
05/
95)
has
been
submitted.
The
results
of
the
ruminant
feeding
study
conducted
at
a
nominal
45
ppm
tebuthiuron
feeding
level
(1.
5x)
for
28
days
show
that
the
existing
tolerances
for
milk
and
meat
are
inadequate
and
that
they
should
be
revised.
The
tolerances
for
meat
and
fat
may
be
lowered,
but
the
tolerances
for
milk
and
meat
byproducts
must
be
increased
as
follows:
Commodity
Existing
Tolerance
1
(40
CFR
§
180.390)
Revised
Tolerance
1
Milk
0.
3
0.
8
Ruminant
2
,fat
2
1.
0
Ruminant
2
,
mbyp
2
5.0
Ruminant
2
,
meat
2
1.0
1
The
tolerance
is
expressed
in
terms
of
tebuthiuron
and
its
metabolites
containing
the
dimethyethyl
thiadiazole
moiety.
2
Separate
tolerances
are
established
for
cattle,
goats,
horses,
and
sheep.
The
feeding
study
have
demonstrated
a
transfer
of
tebuthiuron
to
livestock
tissue
(meat,
meat
byproducts
etc.).
A
dietary
burden
reflecting
theoretical
maximum
exposures
to
tebuthiuron
for
8
beef
cattle
(extrapolating
to
goats,
sheep
and
horse)
was
based
on
reevaluated
tolerances
for
grass
forage
and
grass
hay,
10
ppm
each.
Table
2:
Maximum
Ruminant
Dietary
Burden
for
Tebuthiuron
Commodity
Tolerance
(ppm)
%DM
a
Beef
Cattle
Dairy
Cattle
%Diet
a
Concentration
b
(ppm)
%Diet
a
Concentration
b
(ppm)
Grass
Forage
10
25
60
24
60
24
Grass
Hay
10
88
60
40
4.5
60
40
4.5
TOTAL
100
28.5
100
28.5
a
As
per
Table
1
(OPPTS
Guideline
860.1000)
b
Ruminant
contribution=
[tolerance/
%DM]
x
%diet
No
poultry
or
swine
feed
items
are
associated
with
the
registered
uses
on
grass;
therefore,
there
is
no
reasonable
expectation
of
detectable
residues
of
tebuthiuron
and
its
metabolites
in
poultry,
swine,
and
eggs
resulting
from
the
use
patterns
being
considered
for
reregistration.
These
uses
for
poultry,
swine,
and
eggs
can
be
classified
under
Category
3
of
40
CFR§
180.6(
a).
GLN
860.1500:
Magnitude
of
the
Residue
in
Plants
The
20%
and
40%
P/
T
formulations
(EPA
Reg.
Nos.
62719
121
and
62719
122,
dated
8/
12/
91)
are
registered
for
a
single
broadcast
application
to
rangeland
and
forage
grasses
by
ground
or
air
equipment
at
0.
5
4.
00
lb
ai/
A.
Tebuthiuron
may
be
applied
anytime
but
the
recommended
timing
of
application
is
prior
to
the
resumption
of
active
seasonal
growth
in
the
spring
or
before
expected
seasonal
rainfall.
The
maximum
recommended
rate
is
4.0
lb
ai/
A
for
areas
receiving
20
inches
average
annual
rainfall,
or
2.0
lb
ai/
A
for
areas
receiving
20
inches
average
annual
rainfall.
Fresh
grass
samples
were
collected
every
two
weeks
for
the
first
three
months
following
application,
and
monthly
for
the
following
twenty
one
months
in
order
to
determine
the
maximum
residue
level
that
may
occur
at
anytime
following
application.
Hay
samples
were
collected
up
to
two
years
following
the
application.
The
maximum
combined
residues
found
in/
on
grass
forage
were
9.5
ppm
and
<
8.0
ppm
for
hay
samples
(collected
after
the
first
cutting
in
the
following
season
and
then
after
the
next
two
cuttings).
Application
to
ditches
used
to
transport
irrigation
or
potable
water
is
prohibited.
Treated
grasses
may
not
be
cut
for
hay
for
livestock
feed
for
one
year
after
treatment.
The
Agency
considers
restrictions
against
the
grazing
of
treated
rangeland
to
be
impractical,
and
label
revision
is
required.
9
Currently,
HED's
OPP
Guidelines
860.1000
supports
a
0
day
crop
field
residue
data
for
grasses
cut
for
grass
forage
and
a
reasonable
interval
before
cutting
for
hay.
Tebuthiuron
was
not
sampled
at
a
0
day
time
point
in
the
forage
grass
residue
study
because
sample
timing
was
driven
by
formulation
and
use
pattern
considerations.
Spike
is
an
extruded
pellet
containing
either
20%
or
40%
active
ingredient.
The
pellets
settle
into
the
grass
and
plant
litter
and
are
difficult
to
find
and
essentially
unavailable
from
a
residue
point
of
view.
On
bare
ground
there
would
be
approximately
1
pellet
per
square
foot
per
pound
of
a.
i.
applied.
Residues
do
not
appear
in
plants
until
the
pellets
have
been
activated
by
rainfall
and
the
active
ingredient
washed
into
surface
soil
where
it
is
taken
up
by
plants
(preferable
until
0.5
inches
of
rainfall
had
occurred).
The
registrant
adjusted
the
sampling
schedule
within
the
test
area
reflecting
the
maximum
residue
levels
occurring
at
any
time
after
application
were
tested
(N.
Dodd,
DEB
No.
4587,
2/
9/
89).
HED
supports
the
registrant
hay
residue
study
protocol
and
specifically
allowed
hay
sampling
to
begin
1
year
after
application.
Spike
20P
and
40P
are
used
only
for
woody
plant
infestation
(trees
and
brush).
This
will
allow
re
vegetation
with
desirable
grasses,
but
also
because
the
sparse
grass
in
such
areas
do
not
provide
adequate
nutritional
levels
for
grazing
or
hay
in
that
first
year
(N.
Dodd,
Tebuthiuron
on
Grass
and
Hay,
Memorandum
of
Conference
4/
6/
89).
All
data
requirements
for
the
magnitude
of
the
residue
in
plants
have
been
evaluated
and
deemed
acceptable.
The
conclusions
regarding
the
reregistration
eligibility
of
tebuthiuron
on
the
crops
listed
in
Table
A
are
based
on
the
use
patterns
registered
by
the
basic
producer,
Dow
AgroSciences
LLC.
When
end
use
product
DCIs
are
developed
(e.
g.,
at
issuance
of
the
RED),
RD
should
require
that
all
end
use
product
labels
(e.
g.
MAI
labels,
SLNs
and
products
subject
to
the
generic
data
exemption)
be
amended
such
that
they
are
consistent
with
the
basic
producer
labels.
GLN
860.1520:
Processed
Food/
Feed
No
processed
food/
feed
studies
were
submitted
by
the
registrant.
GLNs
860.1850/
1900:
Confined/
Field
Rotational
Crops
Grasses
in
rangeland
are
not
rotated.
Pastures
on
the
other
hand
can
vary
from
permanent
(>
8
years),
short
term
(2
4
years),
long
term
(5
8
years),
as
well
as
temporary
(<
1
year).
A
rotational
pasture
is
one
used
for
a
few
seasons
and
then
plowed
and
planted
to
another
crop.
10
The
Quantitative
Usage
Analysis
for
Tebuthiuron
indicates
that
the
states
with
the
most
acres
treated
are
in
the
Southwest
U.
S.
(TX,
OK,
NM,
and
AZ).
The
grassland
areas
covered
by
these
states
include
the
Southern
Plains
and
the
Southwest
Grasslands.
These
grassland
areas
are
predominately
rangeland
that
contains
perennial
native
or
introduced
grasses,
that
have
been
invaded
by
woody
perennial
weedy
shrubs
which
are
very
difficult
to
control.
Pastures
are
mostly
perennial
grasses
or
legumes;
however,
we
do
not
know
if
there
are
any
significant
pasture
acreage
planted
to
annual
forages
in
this
region.
Therefore,
confined
field
rotational
crop
studies
will
be
conditionally
required
unless
the
registrant
can
provide
information
that
pastureland
in
this
area
is
either
insignificant
in
acreage
or
is
predominantly
perennial
grasses
that
are
not
rotated
annually.
11
Table
A.
Range
and
Pasture
Typical
and
Maximum
Use
Rates
Use
Site
and
Product
Name
Application
Method
and
Equipment
Registrant
Maximum
Application
For
Use
Rate
Parameters
Label
Maximum
Application
Per
Use
Registrant
Typical
Use
Rate
Reflecting
Label
Typical
Use
Rate
Range
and
Pasture
Spike
20P
(20%
pellet)
Broadcast
and
spot
treatment
Applied
by
hand
using
canister
delivery,
ground
and
aerial
application
For
vulnerable
sites,
maximum
application
rate
is
dependent
upon
annual
precipitation:
<20"
in
annual
precipitation:
no
more
than
1
lb
a.
i./
acre
once
every
3
years
>20"
in
annual
precipitation:
no
more
than
2
lbs
a.
i./
acre
once
every
3
years
For
non
vulnerable
sites,
maximum
application
rate
is
dependent
upon
annual
precipitation:
<20"
in
annual
precipitation
no
more
than
2
lbs
once
every
3
years
and
no
more
than
two
treatments
totaling
6
lbs
a.
i./
acre
in
any
6year
period.
>20"
in
annual
precipitation:
no
more
than
4
lbs
a.
i./
acre
once
every
3
years
and
no
more
than
two
treatments
totaling
6
lbs
a.
i./
acre
in
any
6
year
period
For
broadcast
treatment,
4
lbs
a.
i./
acre
For
spot
treatment
when
needed,
6
lbs
a.
i./
acre
Typical
application
is
once
every
10
20
years
1.0
1.4
lbs
for
oak
use
1.
5
lbs
for
desert
species
0.3
0.5
lbs
for
sage
NS
(continued;
footnotes
follow)
12
TABLE
B.
RESIDUE
CHEMISTRY
SCIENCE
ASSESSMENTS
FOR
REREGISTRATION
OF
TEBUTHIURON.
GLN
Data
Requirements
Current
Tolerances,
ppm
[40
CFR]
Must
Additional
Data
Be
Submitted?
References
1
860.1300:
Plant
Metabolism
No
2
00020645,
00020756,
00020766
860.1300:
Animal
Metabolism
No
00020648,
00020650,
00020651,
00020652,
00020721,
00020767,
00027805,
00027810,
00041675,
00106080,
40985001
40985002
3
860.1340:
Residue
Analytical
Methods
See
footnote
4
00020656,
00020740,
00041673,
00094745,
00106080,
PP#
7F1925,
41196901
5
,
43983701
4
,
43983702
4
860.1380:
Storage
Stability
No
6
42630501
7
,
43439301
6
860.1500:
Magnitude
of
the
Residue
in
Plants
Grass
Forage,
Fodder,
and
Hay
Group
Grass,
forage
10
No
00020757,
00020764,
00041671,
00094745,
42630502
7
Grass,
hay
10
No
00020705,
00094745,
42630502
7
860.1520:
Magnitude
of
the
Residue
in
Processed
Food/
Feed
N/
A
860.1480:
Magnitude
of
the
Residue
in
Meat,
Milk,
Poultry,
and
Eggs
No
8
00041673,
00106080
860.1400:
Magnitude
of
the
Residue
in
Fish
N/
A
860.1400:
Nature
and
Magnitude
of
the
Residue
in
Drinking
and
Irrigation
Water
N/
A
860.1460:
Magnitude
of
the
Residue
in
Food
Handling
Establishments
N/
A
860.1550:
Reduction
of
Residues
N/
A
860.1850:
Rotational
Crops
(Confined)
See
footnote
9
TABLE
B.
(continued).
GLN
Data
Requirements
Current
Tolerances,
ppm
[40
CFR]
Must
Additional
Data
Be
Submitted?
References
1
13
1.
Unless
otherwise
noted,
references
were
reviewed
in
the
Residue
Chemistry
Science
Chapter
of
the
Reregistration
Standard
dated
2/
27/
87.
2.
CBRS
No.
2959,
12/
10/
87,
N.
Dodd.
3.
CBRS
No.
4939,
6/
22/
89,
N.
Dodd.
4.
Enforcement
methods
for
milk
and
animal
tissues
have
been
proposed;
independent
laboratory
validation
is
required.
The
registrant
submitted
submission
MRIDs
43983701
02
which
is
under
reviewed.
5.
Data
pertaining
to
multiresidue
methodology
testing
of
tebuthiuron
and
metabolites
has
been
submitted
and
forwarded
to
FDA
for
review
(M.
Nelson
to
L.
Sawyer,
9/
1/
89).
6.
The
stability
data
fully
supports
the
ruminant
feeding
study,
and
no
additional
data
are
required
(S.
Funk,
CBRS
16937,
11/
22/
95).
7.
CBRS
No.
11314,
D187699,
5/
20/
93,
S.
Funk.
8.
An
adequate
feeding
study
has
been
submitted
(S.
Funk,
D217379,
12/
95).
9.
The
confined
field
rotational
crop
studies
will
be
conditionally
required
unless
the
registrant
can
provide
information
that
pastureland
in
TX,
OK,
and
NM
is
either
insignificant
in
acreage
or
is
predominantly
perennial
grasses
that
are
not
rotated
annually.
860.1900:
Rotational
Crops
(Field)
See
footnote
9
14
TOLERANCE
REASSESSMENT
SUMMARY
HED
has
concluded
that
the
tolerance
expression
for
plants
should
include
tebuthiuron
and
its
metabolites
N[
5(
2
hydroxy
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N,
N'
dimethylurea
[103
(OH)],
N[
5(
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N
methylurea
(104),
and
N[
5(
1,
1dimethylethyl
1,
3,
4
thiadiazol
2
yl]
N'
hydroxymethyl
N
methylurea
(109).
The
tolerance
expression
for
livestock
commodities
should
include
tebuthiuron
and
its
metabolites
104,
N[
5(
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
urea
(106),
2
dimethylethyl
5
amino
1,3,4
thiadiazole
(108),
and
109.
The
terminal
residues
of
concern
in
milk
are
tebuthiuron
and
metabolites
104,
N[
5(
2
hydroxy
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N
methylurea
[104(
OH)],
106,
109,
and
N[
5(
2
hydroxy
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N'hydroxymethyl
N
methylurea
[109(
OH)].
The
adequacy
of
the
established
tolerances
for
milk,
and
the
fat,
meat,
and
meat
byproducts
of
cattle,
goats,
hogs,
horses,
and
sheep
were
from
the
results
of
the
ruminant
feeding
study
conducted
at
a
nominal
45
ppm
tebuthiuron
feeding
level
(1.
5x)
for
28
days
(S.
Funk,
D217379,
12/
05/
95).
The
existing
tolerances
for
milk
(0.
3
ppm)
and
meat
byproducts
(2
ppm)
should
be
increased
to
0.
8
ppm
for
milk
and
5
ppm
for
meat
byproducts.
The
tolerance
for
meat
(2
ppm)
and
fat
(2
ppm)
should
be
lowered
to
1
ppm.
Table
C.
Tolerance
Reassessment
Summary
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Correct
Commodity
Definition
Cattle,
fat
2
1
Cattle,
mbyp
2
5
Cattle,
meat
2
1
Goats,
fat
2
1
Goats,
mbyp
2
5
Goats,
meat
2
1
Horses,
fat
2
1
Horses,
mbyp
2
5
Horses,
meat
2
1
Milk
0.
3
0.
8
Sheep,
fat
2
1
Sheep,
mbyp
2
5
Sheep,
meat
2
1
HED
recommends
that
the
40
CFR
tolerance
expression
under
§180.390
be
modified
as
follows:
15
§
180.390
Tebuthiuron;
tolerances
for
residues
(a)
Tolerances
are
established
for
the
combined
residues
of
the
herbicide
tebuthiuron
N
5(
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl
N,
N'
dimethylurea)
and
its
metabolites
N[
5
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N
methylurea,
N[
5(
1,
1
dimethylethyl)
1,
3,
4thiadiazol
2
yl]
urea,
2
dimethylethyl
5
amino
1,3,4
thiadiazole,
and
N[
5(
1,
1dimethylethyl
1,
3,
4
thiadiazol
2
yl]
N'
hydroxymethyl
N
methylurea
in
or
on
the
following
raw
agricultural
commodities:
Commodity
Parts
per
million
Cattle,
fat
1
Cattle,
mbyp
5
Cattle,
meat
1
Goats,
fat
1
Goats,
mbyp
5
Goats,
meat
1
Horses,
fat
1
Horses,
mbyp
5
Horses,
meat
1
Sheep,
fat
1
Sheep,
mbyp
5
Sheep,
meat
1
(b)
A
tolerance
is
established
for
the
combined
residues
of
the
herbicide
tebuthiuron
N
5(
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl
N,
N'
dimethylurea)
and
its
metabolites
N[
5
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N
methylurea,
N[
5(
2
hydroxy
1,
1dimethylethyl
1,
3,
4
thiadiazol
2
yl]
N
methylurea,
N[
5(
1,
1
dimethylethyl)
1,
3,
4thiadiazol
2
yl]
urea,
N[
5(
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N'
hydroxymethyl
Ndimethylurea
and
N[
5(
2
hydroxy
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N'hydroxymethyl
N
methylurea
in
or
on
the
following
raw
agricultural
commodity:
Commodity
Parts
per
million
Milk
0.
8
16
DIETARY
EXPOSURE
ASSESSMENT
A
refined
acute
and
chronic
dietary
exposure
assessment
was
conducted
for
tebuthiuron
registered
for
foliar
application
to
pastures
and
rangeland
(secondary
transfer
to
livestock
commodities).
Anticipated
residues
from
field
trial
data
and
percent
crop
treated
were
utilized
to
estimate
the
dietary
exposure
to
tebuthiuron
in
the
diets
of
the
U.
S.
Population
(chronic)
and
females
13
50
years
(acute
only)
[S.
Piper,
D281821,
04/
2/
02].
CODEX
HARMONIZATION
No
Codex
MRLs
have
been
established
or
proposed
for
residues
of
tebuthiuron.
Therefore,
issues
of
compatibility
with
respect
to
U.
S.
tolerances
and
Codex
MRLs
do
not
exist.
17
AGENCY
MEMORANDA
CITED
IN
THIS
DOCUMENT
CBRS
No.:
2959
Subject:
EPA
Registration
No.
1471
101
(RCB
No.
2959)
Data
Waiver
or
Amendment
Requested
and
Protocol
Re:
Tebuthiuron
Reregistration
(No
Accession
Number)
From:
N.
Dodd
To:
R.
Taylor
and
Toxicology
Branch
Dated:
12/
10/
87
MRID(
s):
None
CBRS
No.:
None
Subject:
Tebuthiuron
on
Rangelands
and
Pastures
Protocol
for
Magnitude
of
Residues
Studies
for
Tebuthiuron
Reregistration
(No
Accession
Number)
From:
N.
Dodd
To:
R.
Taylor,
Toxicology
Branch
II
Dated:
2/
9/
89
MRID(
s):
None
CBRS
No.:
None
Subject:[
Multiresidue
methodology
testing
of
tebuthiuron
and
six
of
its
metabolites.]
From:
M.
Nelson
To:
L.
Sawyer,
FDA
Dated:
9/
1/
89
MRID(
s):
41196901
CBRS
No.
:
4939
Subject:
EPA
Registration
No.
1471
101
(DEB
No.
4939)
Tebuthiuron
Reregistration
Nature
of
the
Residue
in
Milk
and
Bovine
Tissues.
From:
N.
Dodd
To:
R.
Taylor
and
Toxicology
Branch
II
Dated:
6/
22/
89
MRID(
s):
409850
01
and
409850
02.
CBRS
No.:
11235
DP
Barcode:
D187084
Subject:
Tebuthiuron:
Waiver
Request
for
Grazing
Study
and
Grazing
Study
Protocol;
Draft
of
Enforcement
Analytical
Method
for
Milk;
Schedule
for
Meat
and
Milk
Analytical
Methods;
Schedule
for
Feeding
Study.
From:
S.
Funk
To:
P.
Perreault
Dated:
2/
9/
93
MRID(
s):
None
18
CBRS
No.:
11314
DP
Barcode:
D187699
Subject:
Tebuthiuron:
List
A;
Chemical
105501;
Case
0054.
DowElanco
Response
to
the
Registration
Standard
Data
Requirements
for
Grass
Field
Trials
(171
4(
k))
and
Storage
Stability
for
Forage
and
Hay
(171
4(
e)).
MRID
Nos.
42630501
and
42630502.
From:
S.
Funk
To:
L.
Rossi/
L.
Propst
Dated:
5/
20/
93
MRID(
s):
42630501
and
42630502
CBRS
No.:
15883
DP
Barcode:
D217379
Subject:
Tebuthiuron:
Ruminant
Feeding
Study
(171
4
(j)).
From:
S.
Funk
To:
L.
Propst/
K.
Rothwell
Dated:
12/
5/
95
MRID(
s):
43703201
CBRS
No.:
16937
DP
Barcode:
D223089
Subject:
Tebuthiuron
Storage
Stability
in
Support
of
the
Ruminant
Feeding
Study
(171
4(
e;
j)).
From:
S.
Funk
To:
P.
Deschamp
Dated:
8/
1/
96
MRID(
s):
43439301
CBRS
No.:
None
DP
Barcode:
D281821
Subject:
Tebuthiuron
Acute
and
Chronic
Dietary
Exposure
Assessments
for
the
Tolerance
Reassessment
Eligibility
Decision
(TRED).
From:
S.
Piper
To:
P.
Deschamp/
W.
Livingston
Dated:
4/
2/
02
MRID(
s):
None
| epa | 2024-06-07T20:31:42.639289 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0146-0007/content.txt"
} |
EPA-HQ-OPP-2002-0146-0008 | Supporting & Related Material | "2002-06-25T04:00:00" | null | N
N
S
N
O
N
11
15
01
MEMORANDUM
SUBJECT:
Tebuthiuron.
List
A
Reregistration
Case
0054.
PC
Code
105501.
Product
Chemistry
Chapter
for
the
Tolerance
Renewal
Eligibility
Decision
[TRED]
Document.
DP
Barcode
D277104.
FROM:
K.
Dockter,
Chemist
Reregistration
Branch
2
Health
Effects
Division
[7509C]
THRU:
Alan
Nielsen,
Branch
Senior
Scientist
Reregistration
Branch
2
Health
Effects
Division
[7509C]
TO:
Paula
Deschamp,
Risk
Assessor
Reregistration
Branch
2
Health
Effects
Division
[7509C]
Tebuthiuron
{N[
5(
1,1
dimethylethyl)
1,3,4
thiadiazol
2
yl]
N,
N'
dimethylurea}
is
a
nonselective
herbicide.
Empirical
formula:
C9H16N4OS
Molecular
weight:
228.3
CAS
Registry
No.:
34014
18
1
PC
Code:
105501
Chemical
structure
by
J.
Punzi
A
search
of
REFS
conducted
10/
12/
01
identified
a
single
tebuthiuron
technical
[T]
registered
under
PC
Code
105501,
the
Dow
Agrosciences
LLCo
Spike*
Technical
99
%
T;
EPA
Reg.
No.
2719
109.
It
is
subject
to
a
TRED.
The
Reregistration
Eligibility
Decision
Document
issued
6/
94.
2
The
Registration
Standard
issued
7/
87.
The
product
chemistry
data
base
is
essentially
complete.
There
are
no
reported
impurities
of
toxicological
concern
in
tebuthiuron.
The
Series
830
physical
and
chemical
properties
are
given
in
the
table
below.
GLN
MRID
Data
6302
Color
40493802
off
white
6303
Physical
state
"
crystalline
solid
6304
Odor
"
pungent
7200
MP
"
161.5
164
C
7300
Bulk
density
"
0.579
g/
cc
7840
Water
solubility
"
2.5
mg/
mL
@
25
C
7950
vp
"
2
x
10
6
mm
Hg
@
25
C
7550
log
Pow
"
1.79
6313
Stability
"
stable
for
3
yrs
&
for
6
mo.
@
normal
and
elevated
temperatures,
respectively.
No
light
instability
or
corrosiveness
to
metal
has
been
observed.
cc:
Reg.
Std.
file,
RF,
Dockter,
S.
Piper,
R.
Fricke.
RD\
I
Tebuthiuron
TRED
Team.
7509C:
RRB2:
Rm712N:
57886:
KD/
kd
Tebuthiuron.
TRED
[982]
=
D277104.
mem.
| epa | 2024-06-07T20:31:42.645243 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0146-0008/content.txt"
} |
EPA-HQ-OPP-2002-0146-0009 | Supporting & Related Material | "2002-06-25T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
DATE:
February
25,
2002
SUBJECT:
Tebuthiuron.
(List
A,
Case
No.
0054)
The
Outcome
of
the
HED
Metabolism
Assessment
Review
Committee
Meeting
Held
on
01/
22/
02.
Chemical
1105501.
TXR#
0050409
FROM:
Sheila
Piper,
Chemist,
CEB/
HED
(7509C)
Mark
Corbin,
EPS,
Environmental
Risk
Branch
1
(7507C)
THROUGH:
Francis
B.
Suhre,
Branch
Senior
Scientist
Chemistry
and
Exposure
Branch
Health
Effects
Division
(7509C)
TO:
Yan
W.
Donovan,
Chemist,
RAB1/
HED
(7509C)
Executive
Secretary,
MARC
Material
Reviewed
The
Metabolism
Assessment
Review
Committee
(MARC)
met
on
January
22,
2002
to
consider
the
degradation
of
tebuthiuron
[N[
5(
1,1
dimethylethyl)
1,3,4
thiadiazol
2
yl]
N,
N'dimethylurea
in
water.
Specifically,
MARC
was
asked
to
determine
which
degradates
should
be
included
in
the
risk
assessment.
EFED
supplied
information
that
was
presented
to
MARC
(M.
Corbin,
1/
16/
02)
describing
degradates
found
or
having
the
potential
to
be
found
in
soil
and
water.
MARC
Conclusions
The
Committee
concluded
that
the
parent
compound
and
degradate
104
should
be
included
in
the
drinking
water
risk
assessment.
Although,
MARC
expressed
concern
about
the
toxicity
of
other
metabolites
of
tebuthiuron,
the
Committee
did
not
recommend
including
them
in
a
drinking
water
risk
assessment
because
they
are
not
likely
to
be
present
in
drinking
water.
Supporting
Reasons
Page
2
N
N
S
N
CH
3
CH
3
C
H
3
C
H
3
O
N
H
CH
3
N
N
S
N
CH
3
CH
3
C
H
3
C
H
3
O
NH
2
The
Committee
considered
the
following
information
to
arrive
at
the
conclusion
shown
above:
Available
data
indicate
that
the
parent
and
degradate
104
are
persistent
and
mobile
in
the
environment.
Tebuthiuron
is
frequently
detected
in
ground
and
surface
water
monitoring
studies.
The
degradate
104
was
detected
in
a
retrospective
ground
water
monitoring
study
and
was
a
major
degradate
in
a
terrestrial
field
dissipation
study
accounting
for
up
to
23%
of
the
mass
applied.
The
degradate
104
was
also
found
in
aerobic
soil
metabolism
and
soil
photolysis
studies
comprising
close
to
7%
of
the
mass
applied.
In
addition,
due
to
the
structural
similarity
of
degradate
104
to
tebuthiuron
(104
lacks
an
N
methyl
group)
and
lack
of
toxicity
information
on
degradate
104,
MARC
assumes
that
it
has
similar
toxicity
to
the
parent.
The
chemical
structures
of
tebuthiuron
and
degradate
104
Tebuthiuron:
[N[
5(
1,1
dimethylethyl)
1,3,4
thiadiazol
2
yl]
N,
N'
dimethylurea]
104:
N[
5(
1,1
dimethylethyl)
1,3,4
thiadiazol
2
yl
N
methylurea
Individuals
in
Attendance
1.
MARC
Members
Abdallah
Khasawinah,
Norman
Birchfield,
Christine
Olinger,
Rick
Loranger,
Leung
Cheng,
John
Doherty,
Bill
Wassell,
Yan
Donovan,
David
Nixon,
and
Sheila
Piper.
2.
Scientists
(non
MARC
members)
Ken
Dockter(
RRB2),
Robert
Fricke(
RRB2),
Paula
Deschamp(
RRB2),
and
Mark
Corbin(
EFED).
cc:
SF,
RF,
List
B
File,
S.
Piper,
P.
Deschamp
(RRB2),
Mark
Corbin
(EFED)
RDI:
C.
Olinger:
2/
22/
02;
F.
B.
Suhre:
2/
25/
02
7509C:
CEB1:
CM
2:
Room
810F:
308
2717:
Tebuthiuron
| epa | 2024-06-07T20:31:42.648342 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0146-0009/content.txt"
} |
EPA-HQ-OPP-2002-0146-0010 | Supporting & Related Material | "2002-06-25T04:00:00" | null | 1
THIS
VERSION
INCLUDES
REVISIONS
IN
THE
MUTACGENICITY
AND
DATAGAP
SECTIONS
TXR
No:
0050672
DATE:
April
16,
2002
MEMORANDUM
SUBJECT:
TEBUTHIURON
THIRD
Report
of
the
Hazard
identification
Assessment
Review
Committee
FROM:
Robert
F.
Fricke,
Ph.
D.
Reregistration
Branch
2
Health
Effects
Division
(7509C)
THROUGH:
Jess
Rowland,
Co
Chair
and
Elizabeth
Doyle,
Co
Chair
Hazard
Identification
Assessment
Review
Committee
Health
Effects
Division
(7509C)
TO:
Wilhelmena
Livingston,
Chemical
Review
Manager
Special
Review
and
Registration
Division
(7508C)
PC
CODE:
105501
On
December
13,
2001,
January
17,
2002
and
February
12,
2002,
the
Hazard
Identification
assessment
Review
Committee
(HIARC)
reviewed
the
toxicology
data
base
of
tebuthiuron
and
selected
endpoints/
doses
the
acute
and
chronic
reference
doses.
The
HIARC
also
evaluated
the
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
tebuthiuron
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996.
The
conclusions
drawn
at
these
meetings
are
presented
in
this
report.
2
Committee
Members
in
Attendance
Members
in
attendance:
Ayaad
Assaad,
William
Burnam,
Jonathan
Chen,
Paula
Deschamp
Elizabeth
Doyle
(Co
Chair)
Pamela
Hurley,
John
Liccione,
Elizabeth
Mendez,
David
Nixon
Members
in
absentia:.
Jess
Rowland
(Co
Chair)
Also
in
attendance:
Susan
Makris,
and
Pauline
Wagner
Data
evaluation
/
presentation:
Robert
F.
Fricke
Reregistration
Branch
2
3
N
N
S
N
CH
3
CH
3
C
H
3
C
H
3
O
N
H
CH
3
Tebuthiuron
(105501)
1
INTRODUCTION
On
December
13,
2001
and
January
17,
2002
the
Health
Effects
Division's
(HED)
Hazard
Identification
Assessment
Review
Committee
(HIARC)
reviewed
the
recommendations
of
the
toxicology
reviewer
for
tebuthiuron
with
regard
to
the
acute
and
chronic
Reference
Doses
(RfD).
The
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
tebuthiuron
was
also
evaluated.
The
HIARC
met
again
on
February
12,
2002
to
discuss
the
need
for
an
additional
uncertainty
factor
due
to
the
lack
of
an
acceptable
chronic
toxicity/
carcinogenicity
study
in
rats.
The
conclusions
drawn
at
these
meeting
are
presented
in
this
report.
2
HAZARD
IDENTIFICATION
2.1
Acute
Reference
Dose
(RfD)
Females
13+
Study
Selected:
Rabbit
Developmental
Toxicity
Guideline
No.:
870.3700
(83
4b)
Main
and
Range
Finding
studies
MRID
No.:
00020644,
40776301
Executive
Summary:
In
a
developmental
toxicity
study,
15
presumed
pregnant
Dutch
belted
rabbits
per
group
were
administered
tebuthiuron
(96.5%
a.
i.;
Lot
No.:
B30
23
149)
by
gavage
at
doses
of
0,
10,
or
25
mg/
kg/
day
on
gestation
days
(GD)
6
18,
inclusive.
Doses
were
selected
on
the
basis
of
preliminary
studies
summarized
in
MRID
40776301.
Details
of
the
purity
and
composition
of
the
test
article
and
of
the
insemination
procedure
were
given
in
MRID
41122401.
On
GD
28,
all
surviving
does
were
sacrificed
and
examined
grossly.
Litters
were
weighed
and
each
fetus
examined
for
viability,
sex,
and
external
malformations/
variations.
The
fetuses
were
killed,
examined
viscerally
by
fresh
dissection
(including
the
brain),
and
the
carcasses
processed
for
skeletal
examination.
Doses
were
selected
on
the
basis
of
preliminary
studies
which
were
summarized
in
MRID
40776301.
Mated
rabbits
(4/
group)
were
administered
5,
10,
20,
25,
50,
or
100
mg/
kg/
day
on
GD
6
18.
Three
animals
in
the
100
mg/
kg/
day
group
died
or
were
killed
moribund
on
GD
8
10.
Overall
body
weight
changes
for
the
treated
groups
were
140,
5,
37,
72,
103,
and
480
g,
respectively.
4
In
the
main
study,
premature
deaths
of
several
animals
were
considered
incidental
to
treatment.
No
clinical
signs
of
toxicity
were
observed
in
any
animal.
No
effects
on
body
weights,
body
weight
changes,
or
food
consumption
were
noted
for
the
treated
groups
as
compared
with
the
controls.
No
treatment
related
lesions
were
found
at
gross
necropsy.
No
differences
between
the
treated
and
control
groups
were
noted
for
pregnancy
rate
or
numbers
of
corpora
lutea,
implantations,
fetuses/
litter,
or
resorptions.
Although
the
mean
fetal
body
weights
of
the
high
dose
group
were
83%
of
the
control
level,
the
decrease
was
due
to
a
statistically
significant
(p
#
0.01)
negative
correlation
[increased
litter
size
results
in
a
significant
decrease
in
fetal
body
weight]
between
litter
size
and
fetal
body
weight.
The
total
number
of
fetuses(
litters)
examined
in
the
control,
low,
and
high
dose
groups
was
48(
11),
58(
11),
and
68(
12),
respectively.
No
treatment
related
external,
visceral,
or
skeletal
malformations/
variations
were
observed
in
this
study.
From
the
range
finding
study,
the
percentage
of
early
resorptions
in
the
25,
50,
and
100
mg/
kg/
day
groups
was
68.8,
66.7,
and
100%.
Dose
and
Endpoint
for
Establishing
RfD:
25
mg/
kg/
day,
based
on
increased
number
of
early
resorptions.
Uncertainty
Factor(
s):
100x
(10x
intraspecies
variability,
10x
interspecies
extrapolation).
Comments
about
Study/
Endpoint/
Uncertainty
Factor(
s):
The
HIARC
considered
the
data
of
the
main
study
and
the
range
finding
study
to
establish
this
endpoint.
In
the
main
study,
no
maternal
or
developmental
toxicity
was
seen
at
the
highest
dose;
the
NOAEL
was
25
mg/
kg/
day
(HDT).
In
the
range
finding
study,
early
resorptions
were
observed
at
25
(69%),
50
(67%),
and
100
(100%)
mg/
kg/
day.
Although
the
range
finding
study
indicates
that
25
mg/
kg/
day
is
an
effect
level,
this
dose
(25
mg/
kg/
day)
was
selected
for
risk
assessment,
since
there
was
no
dose
response
in
the
observed
early
resorptions
and
because
there
was
greater
confidence
in
the
results
of
the
main
study
where
no
toxicity
was
seen
at
this
dose
(25
mg/
kg/
day)
and
thus
was
deemed
to
be
an
appropriate
dose
for
risk
assessment.
In
addition,
the
selection
of
the
25
mg/
kg/
day
dose
for
risk
assessment
is
supported
by
the
NOAEL
of
50
mg/
kg/
day
in
a
rabbit
developmental
range
finding
study
with
a
structurally
related
urea
(UC
77179).
This
chemical
had
a
toxicity
profile
similar
to
that
of
tebuthiuron.
At
200
mg/
kg/
day
decreased
body
weight
gain,
lethality
and
early
resorption
were
observed.
5
2.2
Acute
Reference
Dose
(RfD)
General
Population
An
appropriate
end
point
attributable
to
a
single
dose
was
not
available
in
the
database.
The
slight
decrease
(7%)
in
body
weight
gain
seen
on
gestation
day
16
in
the
rabbit
study
is
not
attributable
to
a
single
dose
and
no
maternal
toxicity
was
seen
in
the
rabbit
study.
2.3
Chronic
Reference
Dose
(RfD)
Proposed
Study:
Two
Gen
Repro
Rat
Guideline
No.:
OPPTS
870.3800
(83.4)
MRID
No.:
00090108
Executive
Summary:
In
a
two
generation
reproduction
study,
tebuthiuron
(Lot
No.
00880
1L
1,
X
35920,
98.0%
a.
i.)
was
fed
to
groups
of
25
male
and
25
female
Wistar
rats
per
dose
at
dietary
concentrations
of
0,
100,
200,
and
400
ppm.
The
dietary
levels
corresponded
to
doses
of
6
7,
13
14,
and
26
28
mg/
kg/
day,
respectively,
for
F0
and
F1
males
and
7
8,
14
15,
and
30
31
mg/
kg/
day,
respectively,
for
F0
and
F1
females
averaged
over
the
premating
period
only.
Adult
rats
of
both
generations
were
fed
the
treated
or
control
diets
during
the
premating
period
(98
days
for
F0
and
124
days
for
F1
rats)
and
during
mating,
gestation,
and
lactation
of
two
litters
per
generation.
Pups
from
the
F1a
litters
were
selected
to
parent
the
F2
generation.
No
treatment
related
deaths,
clinical
signs
of
toxicity,
gross
lesions,
or
microscopic
lesions
were
observed
in
adult
rats
of
either
generation.
No
treatment
related
effects
were
observed
on
body
weight,
body
weight
gain,
food
consumption,
or
food
efficiency
in
F0
male
rats,
F1
male
rats,
or
F0
female
rats
fed
any
dose
at
any
time
during
the
study
including
the
premating,
mating,
gestation,
and
lactation
periods.
F1
females
in
the
200
and
400
ppm
groups
had
mean
weekly
body
weights
7
9%
(p
#
.05,
not
biologically
significant)
and
8
13%
(p
#
0.05),
respectively,
less
than
the
control
group
throughout
the
premating
period
starting
with
day
14
(10%,
NS)
for
the
200
ppm
group
and
day
7
(12%,
p
#
0.05)
for
the
400
ppm
group.
Weight
gain
over
the
entire
premating
period
was
7%
(not
significant)
less
than
controls
for
200
ppm
group
F1
females
and
14%
(p
#
0.05)
less
for
the
400
ppm
group.
Cumulative
food
consumption
was
not
significantly
affected,
but
food
efficiency
was
reduced
by
13%
(p
#
0.01)
for
400
ppm
group
F1
females.
The
decreased
body
weights
and
weight
gain
did
not
extend
into
the
gestation
or
lactation
period
for
F2a
litters.
The
parental
systemic
LOAEL
for
tebuthiuron
is
400
ppm
(30
mg/
kg/
day)
based
on
deceases
in
body
weight,
body
weight
gain
and
food
consumption
of
F1
females;
the
NOAEL
is
200
ppm
(14
mg/
kg/
day).
Parental
effect
levels
were
not
established
for
adult
male
rats
in
this
study.
No
effects
were
observed
on
reproductive
parameters
as
measured
by
sperm
morphology,
fertility
index
for
females,
and
the
number
of
litters
produced.
6
Chronic
R
D
14
mg
/
kg
/day(
NOAEL)
100
(UF)
0.14
mg
/
kg
/
day
f
=
=
The
reproductive
LOAEL
for
tebuthiuron
could
not
be
established
for
this
study.
The
NOAEL
is
$
400
ppm
(30
mg/
kg/
day).
The
F1a,
F1b,
F2a,
or
F2b
offspring/
litters
were
not
affected
by
treatment
with
tebuthiuron
in
the
diet.
The
mean
litter
size
at
birth,
litter
size
throughout
lactation,
survival
indices
(live
birth,
viability,
and
lactation),
and
pup
weights
and
pup
weight
gain
throughout
lactation
were
not
statistically
different
between
treated
and
control
groups.
Pups
in
the
400
ppm
group
weighed
about
5
14%
less
than
the
controls
and
gained
slightly
less
weight
than
controls
throughout
lactation.
Mean
litter
sizes
in
the
400
ppm
group
were
larger
than
those
for
the
control
group
and
probably
contributed
to
the
lower
body
weights.
Dosing
was
considered
to
be
barely
adequate
for
assessing
reproductive
and
offspring
toxicity.
The
offspring
LOAEL
could
not
be
established
for
this
study.
The
NOAEL
is
$
400
ppm
(30
mg/
kg/
day).
This
study
is
classified
Acceptable/
Guideline
and
satisfies
the
guideline
requirement
for
a
two
generation
reproductive
study
(OPPTS
870.3800,
§83
4)
in
the
rat.
Dose
and
Endpoint
for
Establishing
RfD:
Parental
systemic
NOAEL
of
14
mg/
kg/
day
based
on
decreased
body
weight,
body
weight
gain
and
food
consumption
in
F1
females
at
30
mg/
kg/
day.
Uncertainty
Factor(
s):
100x
(10x
intraspecies
variability,
10x
interspecies
extrapolation.
Co
mments
about
Study/
Endpoint/
Uncertainty
Factor(
s):
The
HIARC
noted
that
the
chronic
toxicity/
carcinogenicity
study
in
rats
is
unacceptable
since
at
the
doses
tested
(0,
20,
40
or
80
mg/
kg/
day)
no
treatment
related
effects
were
seen
for
mortality,
clinical
signs
or
clinical
pathology.
Treatment
had
no
effects
on
absolute
body
weight
or
body
weight
gains
in
males
and
there
were
minimal
(15%
reduction)
changes
in
absolute
body
weights
in
females
at
termination.
There
were
no
effects
on
neoplastic
and
non
neoplastic
lesions
in
either
sex.
Because
of
the
lack
of
systemic
toxicity,
the
HIARC
determined
that
the
doses
tested
were
inadequate
to
assess
the
chronic
toxicity
or
the
carcinogenic
potential
of
tebuthiuron.
The
NOAEL
of
14
mg/
kg/
day
from
the
two
generation
reproduction
study
used
for
derivation
of
the
chronic
RfD
is
the
lowest
NOAEL
in
the
database.
In
the
1
year
chronic
study
in
dog,
the
NOAEL
was
25
mg/
kg/
day
and
the
LOAEL
was
50
mg/
kg/
day.
In
the
78
week
carcinogenicity
study
in
mice,
the
NOAEL
was
240
mg/
kg/
day
(HDT).
The
HIARC
inferred
that
although
a
repeat
study
in
rats
at
higher
dose
would
provide
hazard
7
characterization
and
evaluate
the
carcinogenic
potential
of
this
pesticide,
but
would
not
yield
a
dose
that
is
lower
than
the
dose
that
is
used
for
derivation
of
the
RfD.
The
chronic
RfD
is
adequate
to
protect
any
adverse
toxicity
effects
following
exposure
to
tebuthiuron.
The
Committee
therefore
concluded
that
an
additional
uncertainty
factor
(for
data
gap)
is
not
needed.
The
HIARC,
however,
determined
that
a
repeat
study
is
required
to
assess
the
carcinogenic
potential
of
tebuthiuron
and
recommended
that
the
request
for
this
study
should
come
as
a
Data
Call
In
notice.
2.4
Occupational/
Residential
Exposure
Toxicological
endpoints
for
occupational/
residential
exposure
risk
assessments
were
not
selected
since
tebuthiuron
is
scheduled
for
a
Tolerance
Reassessment
Eligibility
Decision
(TRED)
3
CLASSIFICATION
OF
CARCINOGENIC
POTENTIAL
3.1
Combined
Chronic
Toxicity/
Carcinogenicity
Study
in
Rats
MRID
No.:
0020714
Executive
Summary:
In
a
chronic
toxicity/
carcinogenicity
study,
tebuthiuron
(>
97%
a.
i.,
lot
number,
6SG43
and
B30
23
149)
was
administered
to
male
and
female
Wistar
rats
(40/
group/
sex)
at
dietary
concentrations
of
400,
800,
or
1600
ppm
(20,
40,
and
80
mg/
kg/
day,
based
on
the
default
food
factor
of
0.05).
Two
control
groups
of
60
male
and
60
female
Wistar
rats
administered
untreated
basal
diet.
No
interim
sacrifice
was
conducted
for
this
study.
Two
replicate
studies
were
carried
out.
No
treatment
related
effects
were
reported
for
clinical
signs,
mortality,
or
clinical
pathology
in
male
or
female
rats
receiving
any
dose
of
the
test
material.
The
mortality
rates
for
all
groups
was
high.
During
the
first
year
of
treatment,
10
19%
of
males
died
while
at
the
end
on
the
study,
only
26%
of
all
rats
remained
alive.
Pneumonia
affected
the
majority
of
animals
in
all
groups
at
various
times
during
the
study;
antibiotic
treatment
was
required
during
one
episode.
Absolute
body
weights
presented
graphically
indicated
that
high
dose
males
and
females
weighed
less
than
controls
throughout
most
of
the
study.
The
magnitude
of
the
reduction
in
absolute
body
weight
could
not
be
determined
for
assessment
of
statistical
or
toxicologic
significance.
A
15%
reductions
in
body
weight
in
high
dose
females
was
observed
at
study
termination.
Food
consumption
was
measured
but
not
reported.
Relative
kidney
weights
were
depressed
in
high
dose
male
rats,
but
no
histopathological
correlates
were
observed.
Each
animal
was
necropsied,
but
gross
findings
were
not
tabulated.
Vacuolization
of
pancreatic
acinar
cells
(generally
slight
or
affecting
only
a
few
cells)
was
observed
in
11
males
and
13
females
receiving
the
high
dose
and
in
none
of
the
controls
of
either
sex.
Only
selected
histopathological
data
were
presented
in
the
summary
tables
of
the
study
report;
therefore,
a
complete
assessment
of
histopathological
findings
could
not
be
conducted.
No
treatment
related
neoplasms
were
reported;
common
neoplasms
included
8
pituitary
adenomas
and
mammary
fibroadenomas
in
female
rats.
The
microscopic
findings
in
the
pancreatic
acinar
cells
were
generally
slight,
affected
only
a
few
cells,
and
caused
no
physiological
effect
on
glucose
levels.
Based
on
the
results
of
this
study
(decreased
terminal
body
weight
in
females),
the
LOAEL
for
systemic
toxicity
was
established
at
80
mg/
kg/
day.
The
NOAEL
was
established
at
40
mg/
kg/
day
in
females.
A
LOAEL
was
not
established
in
males;
the
NOAEL
was
established
at
80
mg/
k/
day.
This
chronic
toxicity/
carcinogenicity
study
in
the
rat
is
Unacceptable/
Guideline
and
does
not
satisfy
the
guideline
requirement
for
a
chronic
toxicity/
carcinogenicity
oral
study
[OPPTS
870.4300
(§
83
5)]
in
the
rat.
Adequacy
of
Dose
Levels:
The
HIARC
disagreed
with
the
1993
RfD
conclusions
that
the
doses
tested
approached
an
adequate
dose
because
of
the
minimal
change
in
female
body
weight.
No
decrease
in
body
weight
was
observed
in
males,
further,
there
was
no
systemic
toxicity.
The
dose
levels
were
selected
from
a
90
day
feeding
study,
where
decreased
body
weight,
organ
weight
changes
and
slight
to
moderate
vacuolization
of
the
pancreatic
cells
was
seen
at
2500
ppm.
Based
on
the
results
of
this
study,
animals
could
have
been
tested
at
higher
doses.
Discussion
of
Tumor
Data:
No
treatment
related
neoplasms
were
reported
at
the
doses
tested.
3.2
Carcinogenicity
Study
in
Mice
MRID
No.
00020717
Executive
Summary:
In
a
carcinogenicity
study,
tebuthiuron
(>
97%
a.
i.,
lot
#
B30
23
149)
was
administered
to
groups
of
80
Harlan
ICR
mice/
sex/
dose
in
pelleted
diet
at
dose
levels
of
400,
800,
or
1600
ppm
(equivalent
to
60,
120,
or
240
mg/
kg
bw/
day
based
on
the
default
food
factor
of
0.15)
for
2
years.
The
control
group,
consisting
of
120
males
and
120
females
was
fed
untreated
pelleted
diet.
Animals
were
equally
subdivided
by
dose
and
sex
into
two
substudies;
the
second
substudy
was
started
1
week
after
the
first.
It
should
be
noted
that
animals
were
not
assigned
by
body
weight.
Although
there
was
a
statistically
significant
decrease
(32.4
g,
12%)
in
the
terminal
body
weights
of
high
dose
females
in
one
of
the
substudies
(M9153),
this
is
likely
due
to
the
higher
body
weight
(36.7
g)
of
the
control
females
in
this
substudy.
The
terminal
body
weight
of
the
control
females
in
the
other
substudy
was
34.1
g.
There
were
no
compound
related
effects
on
mortality,
clinical
signs,
hematology
or
clinical
chemistry,
organ
weights,
or
gross
or
microscopic
pathology.
9
The
LOAEL
for
systemic
toxicity
was
not
established
in
this
study.
The
NOAEL
was
established
at
1600
ppm
(240
mg/
kg/
day).
At
the
doses
tested,
there
was
no
treatment
related
increase
in
tumor
incidence
when
compared
to
that
of
controls.
Dosing
was
not
considered
adequate
based
on
the
absence
of
systemic
effects.
This
carcinogenicity
study
in
the
mouse
is
unacceptable/
guideline
and
does
not
satisfy
guideline
requirements
for
a
carcinogenicity
study
[OPPTS
870.4200;
OECD
451]
in
mice.
Discussion
of
Tumor
Data:
No
treatment
related
neoplasms
were
reported.
Adequacy
of
the
Dose
Levels
Tested:
The
HIARC
disagreed
with
the
1993
RfD
conclusions
that
the
tumor
profile
would
not
change
if
the
dose
was
increased.
At
1600
ppm
there
was
a
12%
decrease
in
female
body
weight;
males
were
unaffected
by
treatment.
The
dose
levels
were
not
considered
adequate
due
to
lack
of
significant
toxicity
at
the
highest
dose
tested.
3.3
Classification
of
Carcinogenic
Potential
The
HIARC
reevaluated
the
classification
and
concluded
that
the
carcinogenic
potential
of
tebuthiuron
can
not
be
determined
due
to
inadequate
carcinogenicity
studies.
The
RfD
Committee
classified
tebuthiuron
as
a
"Group
D"
Carcinogen
Not
classifiable
as
to
human
carcinogenicity
(Second
RfD/
Peer
Review
Report
of
Tebuthiuron,
March
1,
1993).
4
MUTAGENICITY
4.1
Salmonella
typhimurium/
Escherichia
coli
reverse
gene
mutation
assay
[OPPTS
870.5100
(§
84
2)]
MRID
No:
00141691
Executive
Summary:
In
a
reverse
gene
mutation
assay
in
bacteria
,
S.
typhimurium
strains
TA98,
TA100,
TA1535,
TA1537,
and
TA1538
were
exposed
to
tebuthiuron
(98.0%,
lot
number
X
35920)
in
dimethylsulfoxide
(DMSO)
at
concentrations
of
100,
500,
1000,
2500,
or
5000
:
g/
plate
in
the
presence
and
absence
of
mammalian
metabolic
activation
(S9
mix).
Triplicate
plates
were
utilized
for
each
test
concentration.
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
rat
liver.
Tebuthiuron
was
tested
up
to
the
limit
dose.
No
increase
in
mutant
frequency
was
noted
in
any
strain
with
or
without
metabolic
activation.
The
solvent
(DMSO)
and
positive
control
(2
aminoanthracene,
2
nitrofluorene,
9
aminoacridine,
N
methyl
N'nitro
N
nitroso
guanidine
values
were
appropriate
in
the
respective
strains.
There
was
no
evidence
of
induced
mutant
colonies
over
background
in
strains
TA98,
TA100,
TA1535,
TA1537
and
TA1538
with
or
without
S9
activation.
10
This
study
is
classified
as
Acceptable/
Guideline.
It
satisfies
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5100
(§
84
2)]
for
in
vitro
mutagenicity
(bacterial
reverse
gene
mutation)
assay.
4.2
Reverse
Gene
Mutation
Assay
in
Bacteria
[OPPTS
870.5100
(§
84
2)]
MRID
No.:
00141690
Executive
Summary:
In
a
reverse
gene
mutation
assay
in
bacteria,
S.
typhimurium
strains
G46,
TA1535,
TA100,
C3076,
TA1537,
D3052,
TA1538,
and
TA98
and
E.
coli
strains
WP2
and
WP2
uvrA
were
exposed
to
tebuthiuron
(98.0%,
lot
number
X
35920)
in
dimethylsulfoxide
(DMSO)
over
a
concentration
range
of
0.1
to
1000
:
g/
mL,
in
a
gradient
plate
assay,
in
the
presence
and
absence
of
mammalian
metabolic
activation
(S9
mix).
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
rat
liver.
No
increase
in
mutant
frequency
was
noted
in
any
S.
typhimurium
or
E.
coli
tester
strain
with
or
without
metabolic
activation.
The
solvent
(DMSO)
and
positive
control
(2
aminoanthracene,
N
methyl
N'nitro
N
nitrosoguanidine)
values
were
appropriate
in
the
respective
strains.
There
was
no
evidence
of
induced
mutant
colonies
over
background
in
S.
typhimurium
strains
G46,
TA1535,
TA100,
C3076,
TA1537,
D3052,
TA1538,
and
TA98
and
E.
coli
strains
WP2
and
WP2
uvrA
with
or
without
S9
activation.
This
study
is
classified
as
Acceptable/
Nonguideline.
4.3
Mutagenicity
in
vitro
Cytogenetic
Assay
[OPPTS
870.5375]
MRID
No.:
41134101
Executive
Summary:
In
a
mammalian
chromosome
aberration
assay,
Chinese
Hamster
Ovary
(CHO)
cell
cultures
were
exposed
to
tebuthiuron
(99.08%,
lot
number
729AS7)
in
dimethylsulfoxide
at
concentrations
of
0,
1650,
1800,
or
1950
:
g/
mL
for
4
hours
in
the
absence
of
exogenous
metabolic
activation
(S9
mix)
or
to
1350,
1450,
or
1550
:
g/
mL
for
4
hours
in
the
presence
of
activation
(followed
by
an
additional
19
hour
incubation
in
fresh
medium).
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
male
Fischer
344
rat
liver.
Tebuthiuron
was
tested
up
to
concentrations
limited
by
cytotoxicity.
A
preliminary
cytotoxicity
under
nonactivated
conditions
showed
survival
of
15%
at
2285
:
g/
mL,
39%
at
1750
:
g/
mL,
55%
at
1500
:
g/
mL,
and
115%
at
1000
:
g/
mL.
A
significant
(p<
0.01)
increase
in
the
percent
of
cells
with
aberrations
was
noted
in
nonactivated
cultures
at
1950
:
g/
mL
(15
&19%
for
treated
duplicate
cultures
vs.
5%
for
vehicle
controls)
and
activated
cultures
at
1550
:
g/
mL
(15
&18%
for
treated
duplicate
cultures
vs.
5
6%
for
vehicle
controls).
The
predominant
types
of
aberrations
were
chromosome
and
chromatid
breaks.
No
significant
increases
were
observed
at
lower
concentrations;
however,
rare
complex
aberrations,
such
as
triradials,
quadriradials
and
complex
rearrangements
were
noted,
providing
further
support
for
clastogenicity.
Cyclophosphamide
and
mitomycin
C
positive
11
control
values
were
acceptable.
There
was
evidence
of
an
increase
in
structural
chromosomal
aberrations
over
background
in
the
presence
and
absence
of
metabolic
activation
but
only
at
cytotoxic
concentrations.
This
study
is
classified
as
Acceptable/
Guideline.
It
satisfies
the
requirement
for
FIFRA
Test
Guideline
OPPTS
870.5375
(84
2)
for
in
vitro
cytogenetic
mutagenicity
assay.
4.4
In
vitro
Bone
Marrow
Cytogenetic
Assay
[OPPTS
870.5300
(§
84
2)]
MRID
No.:
00145041
Executive
Summary:
In
a
mammalian
cell
gene
mutation
assay
in
vitro,
cultures
of
mouse
lymphoma
L5178Y
TK+/
cells
were
exposed
to
tebuthiuron
(98.0%,
lot
No.
X
35920)
in
dimethylsulfoxide
at
concentrations
of
100,
200,
300,
400,
500,
600,
700,
or
800
:
g/
mL
in
an
initial
assay
the
absence
of
mammalian
metabolic
activation
(S9
mix),
and
at
concentrations
of
10,
100,
200,
300,
400,
500,
750,
or
1000
:
g/
mL
in
an
initial
assay
in
the
presence
of
S9
mix.
Due
to
cytotoxicity,
the
nonactivated
assay
was
repeated
at
concentrations
of
10,
100,
200,
400,
500,
600,
700,
and
800
:
g/
mL,
and
the
activated
assay
was
repeated
at
concentrations
of
1,
10,
100,
200,
400,
500,
600,
or
700
:
g/
mL.
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
rats.
Tebuthiuron
technical
was
tested
up
to
concentrations
limited
by
cytotoxicity.
Relative
growth
ranged
from
57%
to
13%
(at
100
to
800
:
g/
mL)
in
the
absence
of
metabolic
activation
in
the
initial
assay
and
from
28%
to
6%
(at
10
to
750
:
g/
mL)
in
the
presence
of
metabolic
activation
in
the
initial
assay.
In
the
initial
nonactivated
assay,
mutation
indices
of
2.0
and
2.4
were
detected
at
700
and
800
:
g/
mL,
respectively.
In
a
repeat
nonactivated
assay,
mutation
indices
of
2.0,
2.0,
and
2.7
occurred
at
200,
400,
and
500
:
g/
mL,
respectively.
Mutations
were
not
induced
at
any
concentration
with
activation.
The
ethyl
methane
sulfonate
(without
S9)
and
3
methylcholanthrene
(with
S9
mix)
positive
controls
responded
appropriately.
Tebuthiuron
was
considered
weakly
mutagenic
in
the
absence
of
metabolic
activation.
No
evidence
of
an
increased
mutant
frequency
was
observed
in
the
presence
of
metabolic
activation.
This
study
is
classified
as
Acceptable/
Guideline.
It
does
satisfy
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5300
(§
84
2)]
for
in
vitro
mutagenicity
(mammalian
forward
gene
mutation)
data.
4.5
UDS
Assay
Primary
Rat
Hepatocytes
[OPPTS
870.5550
(§
84
2)]
MRID
No.:
40750901
Executive
Summary:
In
an
unscheduled
DNA
synthesis
assay
primary
rat
hepatocyte
cultures
were
exposed
to
tebuthiuron
(99.1%
a.
i.;
Lot
No.
729AS7)
in
dimethylsulfoxide
at
eight
concentrations
ranging
from
300
to
800
:
g/
mL
for
20
hours.
Tebuthiuron
was
tested
to
the
limit
of
cytotoxicity.
Cytotoxicity
was
observed
at
$
900
12
:
g/
mL).
UDS
activity
was
evaluated
at
concentrations
up
to
800
:
g/
mL
and
there
was
no
evidence
of
induction
of
UDS.
The
solvent
(1%
DMSO)
and
positive
control
(N
methyl
N'nitrosoguanidine
1
:
g/
mL
and
2
acetoaminofluorene
0.05
:
g/
mL)
values
were
appropriate.
There
was
no
evidence
that
unscheduled
DNA
synthesis,
as
determined
by
radioactive
tracer
procedures
[nuclear
silver
grain
counts]
was
induced.
This
study
is
classified
as
Acceptable/
Guideline.
It
does
satisfy
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5550
(§
84
2)]
for
other
genotoxic
mutagenicity
data.
4.6
Sister
Chromatid
Exchange
[OPPTS
870.5900
(§
84
2)]
MRID
No.:
40750902
Executive
Summary:
In
an
in
vivo
cytogenetic
assay
measuring
sister
chromatid
exchange
(SCE)
frequency
in
Chinese
hamster
bone
marrow
cells
female
Chinese
hamsters
(3/
group)
were
administered
single
oral
doses
of
tebuthiuron
(99.1%,
Lot
No.
729AS7)
in
10%
aqueous
acacia
at
3000,
4000,
or
5000
mg/
kg.
Tebuthiuron
was
tested
up
to
cytotoxic
concentrations.
Hypoactivity
was
noted
in
all
treatment
groups
and
bone
marrow
cytotoxicity
(as
evidenced
by
an
increase
in
the
percent
division
metaphases)
was
observed
at
5000
mg/
kg.
There
was
no
increase
in
the
number
of
cells
containing
SCEs
compared
to
controls
at
any
concentration
of
tebuthiuron
tested.
Cyclophosphamide
(50
mg/
kg)
and
vehicle
control
values
were
acceptable.
There
was
no
evidence
of
an
increase
in
SCEs
over
background.
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5915
(§
84
2)]
for
in
vivo
cytogenetic
mutagenicity
data.
4.7
Conclusions:
The
submitted
test
battery
satisfies
the
Pre
1991
mutagenicity
initial
testing
battery
guidelines.
Tebuthiuron
was
not
mutagenic
in
bacteria,
but
was
weakly
positive
for
gene
mutations
in
cultured
mouse
lymphoma
cells.
The
effect
in
mammalian
cells
was,
however,
confined
to
non
activated
test
conditions.
There
was
also
some
evidence
of
a
clastogenic
response
at
cytotoxic
doses
both
with
and
without
S9
activation.
Since
an
acceptable
in
vivo
bone
marrow
cytogenetic
assay
is
not
available,
final
conclusions
regarding
the
mutagenic
potential
of
tebuthiuron
can
not
be
made
at
this
time.
13
5
FQPA
CONSIDERATIONS
5.1
Adequacy
of
the
Data
Base
The
toxicology
data
base
is
adequate
for
an
FQPA
assessment.
The
required
developmental
toxicity
study
in
the
rabbit
does
not
meet
guideline
requirements.
6
FQPA
CONSIDERATIONS
6.1
Neurotoxicity
Data
No
acute
or
subchronic
neurotoxicity
studies
on
tebuthiuron
are
available.
Evaluation
of
subchronic,
chronic
and
reproduction
toxicity,
did
not
indicate
any
treatment
related
effects
on
the
central
or
peripheral
nervous
system
of
mice,
rats,
or
rabbits.
No
changes
in
clinical
signs,
brain
weights,
gross
necropsy
results
or
histopathological
results
suggested
that
any
part
of
the
nervous
system
as
a
target
organ.
6.2
Developmental
Toxicity
6.2.1
Prenatal
Developmental
Study
Rat
MRID
No:
00020803,
40485801
Executive
Summary:
In
a
developmental
toxicity
study,
25
presumed
pregnant
Harlan
rats
per
group
were
administered
tebuthiuron
(purity
not
given;
Lot
No.
1093
316A
259)
at
dietary
concentrations
of
0,
600,
1200,
or
1800
ppm
on
gestation
days
(GD)
6
15,
inclusive.
Doses
to
the
animals
were
0,
37,
72,
or
110
mg/
kg/
day
(calculated
from
body
weight
and
feed
consumption
data),
respectively.
On
GD
20,
dams
were
sacrificed
and
subjected
to
gross
necropsy;
pancreatic
tissue
was
saved
from
10
females/
group
for
histopathological
examination.
Fetal
sex,
weight,
and
viability
were
determined
and
each
fetus
was
examined
for
external
abnormalities.
Approximately
one
third
of
all
fetuses
were
fixed
in
Bouin's
solution
for
subsequent
visceral
examination
and
the
remainder
were
cleared
for
skeletal
examination.
All
dams
survived
to
terminal
sacrifice.
No
treatment
related
clinical
signs
of
toxicity
were
observed
in
any
group.
Body
weights,
body
weight
gains,
and
food
consumption
by
the
low
and
mid
dose
groups
were
similar
to
the
controls
throughout
the
study.
No
treatment
related
lesions
were
observed
in
any
dam
at
necropsy.
Pancreatic
tissue,
as
evaluated
by
both
gross
and
microscopic
examination,
appeared
normal.
For
the
high
dose
group,
absolute
body
weights
were
slightly
reduced
on
GD
16
to
93%
of
the
control
level
due
to
reduced
body
weight
gains
during
the
entire
treatment
interval.
Body
weight
gains
by
the
high
dose
dams
were
21%
of
the
control
level
during
GD
6
10
and
57%
of
the
control
level
during
GD
11
15.
During
the
treatment
interval,
food
14
consumption
by
the
high
dose
group
was
71%
of
the
control
amount
for
GD
6
10
and
95%
of
the
control
amount
for
GD
11
15.
Compensatory
weight
gain
and
food
consumption
was
observed
in
the
high
dose
group
during
the
post
treatment
interval.
The
maternal
toxicity
LOAEL
is
1800
ppm
(110
mg/
kg/
day)
based
on
decreased
body
weight
gains
and
food
consumption.
The
maternal
toxicity
NOAEL
is
1200
ppm
(72
mg/
kg/
day).
No
differences
were
observed
between
the
treated
and
control
groups
for
pregnancy
rate,
number
of
corpora
lutea/
dam,
number
of
implantation
sites/
dam,
pre
or
postimplantation
losses,
number
of
fetuses/
litter,
fetal
body
weights,
or
fetal
sex
ratios.
No
dead
fetuses
were
observed.
The
total
number
of
fetuses(
litters)
available
for
examination
for
malformations/
variations
in
the
control,
low,
mid,
and
high
dose
groups
was
259(
23),
263(
21),
300(
23),
and
258(
21),
respectively.
No
treatment
related
abnormalities
were
found
in
any
fetus.
In
the
control,
low,
mid,
and
high
dose
groups,
the
total
number
of
fetuses(
litters)
with
external,
visceral,
or
skeletal
malformations/
variations
was
3(
2),
4(
4),
11(
7),
and
4(
3),
respectively.
Hydronephrosis
was
a
common
finding
in
fetuses
from
control
and
treated
groups
The
developmental
toxicity
NOAEL
is
$
1800
ppm
(110
mg/
kg/
day)
and
the
developmental
toxicity
LOAEL
was
not
identified.
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
requirements
for
a
developmental
toxicity
study
[870.3700
(§
83
3a)]
in
rats.
6.2.2
Developmental
Toxicity
Study
in
the
Rabbit
MRID
No.:
00020644
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
00020644),
15
presumed
pregnant
Dutch
belted
rabbits
per
group
were
administered
tebuthiuron
(96.5%
a.
i.;
Lot
No.:
B30
23
149)
by
gavage
at
doses
of
0,
10,
or
25
mg/
kg/
day
on
gestation
days
(GD)
6
18,
inclusive.
Details
of
the
purity
and
composition
and
of
the
insemination
procedure
were
given
in
MRID
41122401.
On
GD
28,
all
surviving
does
were
sacrificed
and
examined
grossly.
Litters
were
weighed
and
each
fetus
examined
for
viability,
sex,
and
external
malformations/
variations.
The
fetuses
were
killed,
examined
viscerally
by
fresh
dissection
(including
the
brain),
and
the
carcasses
processed
for
skeletal
examination.
Doses
for
the
main
study
were
selected
on
the
basis
of
a
preliminary
range
finding
study
(MRID
40776301).
In
this
study,
mated
rabbits
(4/
group)
were
administered
5,
10,
20,
25,
50,
or
100
mg/
kg/
day
on
GD
6
18.
Three
animals
in
the
100
mg/
kg/
day
group
died
or
were
killed
moribund
on
GD
8
10.
Overall
body
weight
changes
for
the
treated
15
groups
were
140,
5,
37,
72,
103,
and
480
g,
respectively.
The
percentage
of
resorptions
in
the
25,
50,
and
100
mg/
kg/
day
groups
was
68.8,
66.7,
and
100%..
In
the
main
study,
premature
deaths
of
several
animals
were
considered
incidental
to
treatment.
No
clinical
signs
of
toxicity
were
observed
in
any
animal.
No
effects
on
body
weights,
body
weight
changes,
or
food
consumption
were
noted
for
the
treated
groups
as
compared
with
the
controls.
No
treatment
related
lesions
were
found
at
gross
necropsy.
The
maternal
toxicity
NOAEL
was
established
at
25
mg/
kg/
day;
the
LOAEL
for
maternal
toxicity
was
not
established.
No
differences
between
the
treated
and
control
groups
were
noted
for
pregnancy
rate
or
numbers
of
corpora
lutea,
implantations,
fetuses/
litter,
or
resorptions.
Although
the
mean
fetal
body
weights
in
the
high
dose
group
were
significantly
lower
than
the
control
value,
the
decreases
were
attributed
to
increased
liter
size.
The
total
number
of
fetuses(
litters)
examined
in
the
control,
low,
and
high
dose
groups
was
48(
11),
58(
11),
and
68(
12),
respectively.
No
treatment
related
external,
visceral,
or
skeletal
malformations/
variations
were
observed
in
this
study.
The
developmental
toxicity
NOAEL
is
established
at
25
mg/
kg/
day;
the
LOAEL
was
not
established.
This
study
is
classified
as
Unacceptable/
Guideline
and
does
not
satisfy
the
guideline
requirements
for
a
developmental
toxicity
study
[870.3700
(§
83
3b)]
in
rabbits.
6.3
Reproductive
Toxicity
6.3.1
Two
Generation
Reproduction
Rat
MRID
No:
90108
Executive
Summary:
In
a
two
generation
reproduction
study,
tebuthiuron
(Lot
No.
00880
1L
1,
X
35920,
98.0%
a.
i.)
was
fed
to
groups
of
25
male
and
25
female
Wistar
rats
per
dose
at
dietary
concentrations
of
0,
100,
200,
and
400
ppm.
The
dietary
levels
corresponded
to
doses
of
6
7,
13
14,
and
26
28
mg/
kg/
day,
respectively,
for
F0
and
F1
males
and
7
8,
14
15,
and
30
31
mg/
kg/
day,
respectively,
for
F0
and
F1
females
averaged
over
the
premating
period
only.
Adult
rats
of
both
generation
were
fed
the
treated
or
control
diets
during
the
premating
period
(98
days
for
F0
and
124
days
for
F1
rats)
and
during
mating,
gestation,
and
lactation
of
two
litters
per
generation.
Pups
from
the
F1a
litters
were
selected
to
parent
the
F2
generation.
16
No
treatment
related
deaths,
clinical
signs
of
toxicity,
gross
lesions,
or
microscopic
lesions
were
observed
in
adult
rats
of
either
generation.
No
treatment
related
effects
were
observed
on
body
weight,
body
weight
gain,
food
consumption,
or
food
efficiency
in
F0
male
rats,
F1
male
rats,
or
F0
female
rats
fed
any
dose
at
any
time
during
the
study
including
the
premating,
mating,
gestation,
and
lactation
periods.
F1
females
in
the
2
00
and
400
ppm
groups
had
mean
weekly
body
weights
7
9%
and
8
13%
(p<
0.01
or
<0.05),
respectively,
less
than
the
control
group
throughout
the
premating
period
starting
with
day
21
for
the
200
ppm
group
and
day
7
for
the
400
ppm
group.
Weight
gain
over
the
entire
premating
period
was
7%
(N.
S.)
less
than
controls
for
200
ppm
group
F1
females
and
14%
(p<
0.05)
less
for
the
400
ppm
group.
Cumulative
food
consumption
was
not
significantly
affected,
but
food
efficiency
was
reduced
by
13%
(p<
0.01)
for
400
ppm
group
F1
females.
The
decreased
body
weights
and
weight
gain
did
not
extend
into
the
gestation
or
lactation
period
for
F2a
litters.
The
parental
systemic
LOAEL
for
tebuthiuron
is
400
ppm
(30
mg/
kg/
day)
for
female
rats
based
on
deceases
in
body
weight
and
weight
gain;
the
corresponding
NOAEL
is
200
ppm
(14
mg/
kg/
day).
Parental
effect
levels
were
not
established
for
adult
male
rats
in
this
study.
No
effects
were
observed
on
reproductive
parameters
as
measured
by
sperm
morphology,
fertility
index
for
females,
and
the
number
of
litters
produced.
The
reproductive
LOAEL
for
tebuthiuron
could
not
be
established
for
this
study.
The
NOAEL
is
$
400
ppm
(30
mg/
kg/
day)
The
F1a,
F1b,
F2a,
or
F2b
offspring/
litters
were
not
affected
by
treatment
with
tebuthiuron
in
the
diet.
The
mean
litter
size
at
birth,
litter
size
throughout
lactation,
survival
indices
(live
birth,
viability,
and
lactation),
and
pup
weights
and
pup
weight
gain
throughout
lactation
were
not
statistically
different
between
treated
and
control
groups.
Mean
litter
size
in
400
ppm
group
was
larger
than
those
for
the
control
group
and
probably
contributed
to
the
lower
body
weights.
Dosing
was
considered
to
be
barely
adequate
for
assessing
reproductive
and
offspring
toxicity.
The
offspring
LOAEL
could
not
be
established
for
this
study.
The
NOAEL
is
$
400
ppm.
(30
mg/
kg/
day).
This
study
is
classified
Acceptable/
Guideline
and
satisfies
the
guideline
requirement
for
a
two
generation
reproductive
study
(OPPTS
870.3800,
§83
4)
in
the
rat.
6.4
Additional
Information
from
Literature
Sources
No
studies
available
17
6.5
Determination
of
Susceptibility
There
is
no
qualitative/
quantitative
evidence
of
increased
susceptibility
following
in
utero
exposure
to
rats
or
following
pre/
post
natal
exposure
to
rats
in
the
2
generation
reproduction
study.
Susceptibility
could
not
be
assessed
due
to
the
lack
of
maternal
or
developmental
toxicity
at
the
highest
dose
tested..
6.6
Evidence
That
Suggest
Study
Requiring
a
Developmental
Neurotoxicity
Study
The
need
for
a
developmental
neurotoxicity
study
is
being
held
in
reserve,
pending
submission
of
developmental
toxicity
studies
in
the
rabbit
(data
gap).
6.7
Evidence
That
Do
Not
Suggest
Requiring
a
Developmental
Neurotoxicity
Study:
(1)
No
neurological
signs
or
neuropathy
were
observed
in
any
of
the
studies.
(2)
No
increased
susceptibility
in
rat
developmental
study.
(3)
No
increased
susceptibility
the
2
generation
reproduction
study
in
the
rat.
7
HAZARD
CHARACTERIZATION
The
toxicological
database
for
tebuthiuron
is
not
considered
adequate
for
hazard
characterization.
The
developmental
toxicity
studies
in
the
rat
and
rabbit
as
well
as
the
chronic
feeding
study
in
the
rat
and
oncogenicity
studies
in
the
rat
and
mouse
were
found
to
be
unacceptable.
Further,
because
tebuthiuron
was
weakly
positive
for
gene
mutations
in
cultured
mouse
lymphoma
cells,
an
in
vivo
mammalian
bone
marrow
chromosomal
aberration
assay
is
also
required.
The
acute
toxicity
studies
indicate
that
tebuthiuron,
technical,
is
more
toxic
for
oral
(Toxicity
Category
II)
exposure
than
for
either
dermal
(Toxicity
Category
IV)
or
inhalation
(Toxicity
Category
III).
The
primary
eye
and
skin
irritation
studies
were
both
Toxicity
Category
IV;
no
dermal
sensitization
occurred
with
tebuthiuron
in
guinea
pigs.
Although
the
most
consistent
toxicological
effect
was
decreased
body
weight,
histopathological
changes
in
the
pancreas
were
observed
in
the
rat.
Vacuolation
of
pancreatic
acinar
cells
was
observed
in
both
the
subchronic
and
chronic
feeding
studies.
Vacuolation
was
described
as
slight
or
affecting
only
a
few
cells.
Subchronic
feeding
studies
are
available
in
the
rat
and
dog,
as
well
as
a
21
day
dermal
toxicity
study
in
the
rabbit.
In
the
rat
study,
reduced
body
weight,
increases
in
relative
liver,
kidney
and
gonad
weights,
and
slight
vacuolation
of
pancreatic
acinar
cells
were
observed
in
both
sexes;
males
also
had
increased
relative
spleen
and
prostate
gland
weights.
In
the
dog
study,
anorexia,
18
weight
loss,
increases
in
blood
urea
nitrogen
and
alkaline
phosphatase,
and
increases
in
spleen
and
thyroid
gland
weights
were
observed.
In
the
21
day
dermal
toxicity
study
in
rabbits,
no
dermal
or
systemic
toxicity
was
observed
at
1000
mg/
kg/
day
(limit
dose).
Tebuthiuron
toxicity
was
also
evaluated
in
a
combined
chronic
toxicity/
oncogenicity
study
in
the
rat
and
a
chronic
feeding
study
in
the
dog.
Decreased
body
weights
were
observed
in
both
the
rat
and
dog.
Vacuolization
of
pancreatic
acinar
cells
(generally
slight
or
affecting
only
a
few
cells)
was
observed
in
rats,
while
increased
liver
and
thyroid
weights
were
observed
in
the
dog.
At
the
doses
tested,
neither
the
rat
nor
mouse
showed
any
treatment
related
increase
in
the
incidence
of
neoplasms.
However,
these
dose
levels
were
too
low
to
assess
the
carcinogenic
potential
of
tebuthiuron.
Rat
and
rabbit
developmental
toxicity
studies
were
carried
out
with
tebuthiuron.
In
the
rat,
no
compound
related
developmental
effects
were
observed.
In
the
rabbit
susceptibility
could
not
be
evaluated
due
to
lack
of
maternal
and
developmental
toxicity
at
the
high
dose
tested.
In
a
two
generation
study
in
the
rat,
the
only
toxicological
effect
observed
was
a
statistically
and
biologically
significant
decrease
in
the
mean
body
weight
of
throughout
the
premating
period;
no
offspring
toxicity
was
seen.
Tebuthiuron
was
not
mutagenic
in
bacteria,
but
was
weakly
positive
for
gene
mutations
in
cultured
mouse
lymphoma
cells.
The
effect
in
mammalian
cells
was,
however,
confined
to
nonactivated
test
conditions.
There
was
also
some
evidence
of
a
clastogenic
response
at
cytotoxic
doses
both
with
and
without
S9
activation.
Since
an
acceptable
in
vivo
bone
marrow
cytogenetic
assay
is
not
available,
final
conclusions
regarding
the
mutagenic
potential
of
tebuthiuron
can
not
be
made
at
this
time.
8
DATAGAPS
The
HIARC
identified
the
following
data
gaps:
28
day
inhalation
study
in
the
rat
due
to
potential
long
term
inhalation
exposure
based
on
the
current
use
pattern..
Developmental
toxicity
study
in
the
rabbit
the
current
study
is
unacceptable
and
is
not
adequate
to
assess
susceptibility
for
FQPA.
Chronic
feeding/
oncogenicity
study
in
the
rat
doses
tested
were
not
adequate
to
assess
the
carcinogenic
potential.
Carcinogenicity
study
in
the
mouse
doses
tested
were
not
adequate
to
assess
the
carcinogenic
potential.
In
vivo
bone
marrow
chromosomal
aberration
test
Tier
II
test,
required
to
verify
the
positive
response
in
the
in
vitro
chromosomal
assay.
Developmental
neurotoxicity
study
in
Reserve
pending
submission
of
developmental
19
toxicity
in
the
rabbit.
9
ACUTE
TOXICITY
Acute
Toxicity
of
Tebuthiuron,
Technical
Guideline
No.
Study
Type
MRID
No.
Results
Toxicity
Category
870.1100
Acute
Oral
(Rat)
40583901
LD50
=
477.5
mg/
kg
(
%
%
)
387.5
mg/
kg
(
&
&
)
II
870.1200
Acute
Dermal
(Rabbit)
40583902
LD50
=
>
5000
mg/
kg
(
%
%
and
&
&
)
IV
870.1300
Acute
Inhalation
(Rat)
00155730
LC50
=
3.
696
mg/
L
III
870.2400
Primary
Eye
Irritation
40583903
Slight
irritation
IV
870.2500
Primary
Skin
Irritation
40583902
Non
irritating
IV
870.2600
Dermal
Sensitization
40583904
Non
sensitizing
–
20
10
SUMMARY
OF
TOXICOLOGY
ENDPOINT
SELECTION
The
doses
and
toxicological
endpoints
selected
for
Tebuthiuron
EXPOSURE
SCENARIO
DOSE
(mg/
kg/
day)
ENDPOINT
STUDY
Acute
Dietary
(Females
13
50)
NOAEL=
25
UF
=
100
Increased
post
implantation
loss
and
fetal/
litter
resorptions
at
50
mg/
kg/
day
(LOAEL).
Developmental
Toxicity
Study
in
the
Rabbit
Acute
RfD
(Females
13
50
years
old)
=
0.25
mg/
kg
Acute
Dietary
(General
Population)
No
appropriate
effects
attributed
to
a
single
exposure
was
identified.
Chronic
Dietary
NOAEL
=
14
UF
=
100
Decreased
body
weight
and
feed
consumption
in
F1
females
at
30
mg/
kg/
day
(LOAEL)
2
Generation
Reproduction
Study
in
the
Rat
Chronic
RfD
=
0.
14
mg/
kg/
day
Toxicological
endpoints
for
occupational/
residential
exposure
risk
assessments
were
not
selected
since
tebuthiuron
is
scheduled
for
a
Tolerance
Reassessment
Eligibility
Decision
(TRED)
| epa | 2024-06-07T20:31:42.652078 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0146-0010/content.txt"
} |
EPA-HQ-OPP-2002-0146-0011 | Supporting & Related Material | "2002-06-25T04:00:00" | null | TXR
NO.
0050466
February
12,
2002
MEMORANDUM
SUBJECT:
TEBUTHIURON
Report
of
the
FQPA
Safety
Factor
Committee.
FROM:
Carol
Christensen,
Acting
Executive
Secretary
FQPA
Safety
Factor
Committee
Health
Effects
Division
(7509C)
THROUGH:
Ed
Zager,
Chairman
FQPA
Safety
Factor
Committee
Health
Effects
Division
(7509C)
TO:
Paula
Deschamp,
Risk
Assessor
Reregistration
Branch
II
Health
Effects
Division
(7509C)
PC
Code:
105501
The
Health
Effects
Division
(HED)
FQPA
Safety
Factor
Committee
met
on
February
4
th
,
2002
to
evaluate
the
hazard
and
exposure
data
for
tebuthiuron.
The
Committee
recommend
that
the
FQPA
Safety
Factor
(as
required
by
the
FQPA)
be
reduced
to
3x
when
assessing
the
exposure
and
risks
of
this
chemical
to
human
health.
2
I.
HAZARD
ASSESSMENT
(Correspondence:
R.
Fricke
to
C.
Christensen
dated
January
31,
2002)
A.
Adequacy
of
Database
The
Hazard
Identification
Assessment
Review
Committee
(HIARC)
met
on
December
13
th
,
2001
and
on
January
7
th
,
2002
to
review
the
toxicological
database
of
tebuthiuron.
The
toxicological
database
is
adequate
for
FQPA
assessment,
however
there
are
significant
data
gaps.
The
developmental
toxicity
study
in
the
rabbit
is
unacceptable
for
the
determination
of
susceptibility
to
the
fetuses
due
to
in
utero
tebuthiuron
exposure.
However,
there
is
an
adequate
developmental
toxicity
study
in
the
rat
and
a
twogeneration
reproductive
toxicity
study
in
the
rat
to
assess
the
susceptibility
of
fetuses/
offspring
to
tebuthiuron.
The
Committee
reserved
the
requirement
of
a
developmental
neurotoxicity
study
due
to
the
data
gap
for
a
developmental
toxicity
study
in
rabbits.
B.
Determination
of
Susceptibility
There
is
no
qualitative/
quantitative
evidence
of
increased
susceptibility
in
the
2
generation
reproduction
study
in
the
rat
or
the
developmental
toxicity
study
in
the
rat.
In
the
developmental
toxicity
study
in
the
rabbit,
no
maternal
or
developmental
toxicity
was
observed
at
the
highest
dose
tested.
Because
there
was
no
toxicity
observed
at
the
highest
dose
tested,
susceptibility
could
not
be
ascertainted
and
the
HIARC
concluded
that
a
new
developmental
toxicity
in
the
rabbit
is
needed.
II.
EXPOSURE
ASSESSMENT
(Correspondence:
S.
Piper
to
C.
Christensen
dated
January
31,
2002)
A.
Dietary
Exposure
Considerations
Tebuthiuron
is
an
herbicide
registered
for
use
on
pastures
and
rangeland.
The
chemical
is
registered
for
a
single
broadcast
application
to
rangeland
and
forage
grasses
by
ground
or
air
equipment
with
an
application
rate
of
0.75
4.00
lb
ai/
A.
The
recommended
timing
of
application
is
prior
to
the
resumption
of
active
seasonal
growth
in
the
spring
or
before
expected
seasonal
rainfall.
Tolerances
range
from
0.8
5.0
ppm
for
secondary
residues
and
10
ppm
for
forage.
There
are
no
Codex
MRLs
established
or
proposed
for
residues
of
tebuthiuron.
Therefore,
issues
of
compatibility
with
respect
to
U.
S.
tolerances
and
Codex
MRLs
do
not
exist.
The
qualitative
nature
of
the
residue
in
grasses
is
adequately
understood.
The
residues
of
concern
are
the
parent
compound
and
its
metabolites
103(
OH),
104,
and
109.
The
terminal
residues
of
concern
in
fat,
meat,
kidney,
and
liver
are
tebuthiuron
and
its
metabolites
104,
106,
108
and
109;
the
terminal
residues
of
concern
in
milk
are
3
tebuthiuron
and
metabolites
104,
104(
OH),
106,
109
and
109(
OH).
Tebuthiuron
is
a
systemic
soil
herbicide
that
is
absorbed
mainly
by
the
roots,
with
ready
translocation.
There
are
no
monitoring
data
(PDP
or
FDA)
for
Tebuthiuron.
Percent
of
crop
treated
information
is
available
for
use
in
the
assessment.
A
DEEM
Tier
II
analysis
will
likely
be
used
to
assess
dietary
exposure
to
this
chemical
using
the
results
of
field
trial
studies
and
percent
of
crop
treated
data.
The
Committee
recognizes
that
further
refinement
to
the
dietary
food
exposure
analyses
may
be
required
as
the
risk
assessment
is
developed.
Therefore,
provided
the
final
dietary
food
exposure
assessment
includes
the
metabolites
of
toxicological
concern
and
does
not
underestimate
the
potential
risk
for
infants
and
children,
the
safety
factor
recommendations
of
this
Committee
stand.
B.
Drinking
Water
Exposure
Considerations
The
environmental
fate
database
is
essentially
complete
for
parent
tebuthiuron.
Tebuthiuron
water
degradate
104
was
detected
at
6.9%
and
rising
by
the
end
of
the
study.
The
HED
Metabolism
Assessment
and
Review
Committee
(MARC)
recommended
degradate
104
be
included
in
the
water
exposure
and
risk
assessment.
Based
on
the
available
data,
the
parent
and
degradate
104
are
persistent
and
mobile.
The
quickest
observed
route
of
tebuthiuron
degradation
in
laboratory
studies
was
soil
photolysis
halflife
39.7
days.)
Tebuthiuron
has
been
assessed
through
a
combination
of
modeling
and
analysis
of
surface
water
and
ground
water
monitoring
data.
Drinking
water
monitoring
results
are
not
available
for
the
chemical
for
direct
quantitative
incorporation
into
the
exposure
and
risk
assessment.
Therefore,
drinking
water
exposure
assessments
are
supplemented
with
modeling
predictions.
Surface
water
concentrations
of
tebuthiuron
were
modeled
using
the
PRZM/
EXAMS
(Tier
II)
programs
for
pasture/
rangeland
using
EFED's
standard
scenario
for
alfalfa
in
Texas.
Groundwater
concentrations
were
modeled
using
the
SCIGROW
program.
Input
parameters
used
Tier
II
(PRZM
version
3.12/
EXAMS
version
2.97.5)
modeling
were
selecting
using
Agency
guidance
and
EFED
calculated
degradation
rate
constants
from
review
of
registrant
submitted
environmental
fate
studies.
This
assessment
strategy
was
designed
to
assess
concentrations
of
the
parent
compound.
In
order
to
account
for
the
degradate
of
toxicological
concern,
EFED
will
complete
modeling
of
the
degradate
using
the
total
residue
approach.
Total
residues
(parent
plus
all
degradates
of
toxicological
concern)
are
summed
from
fate
studies.
In
this
case
fate
parameters
are
estimated
for
total
residues
for
aerobic
soil
metabolism,
aerobic
aquatic
metabolism,
anaerobic
soil
metabolism,
and
photolysis.
Other
required
fate
parameters
are
conservatively
estimated
as
stable
in
accordance
with
EFED
guidance.
This
method
4
provides
conservative
estimates
of
total
residues
(parent
plus
degradates)
in
surface
and
ground
water.
Drinking
water
monitoring
data
support
the
results
of
the
drinking
water
models.
The
FQPA
Safety
Factor
Committee
recognizes
that
further
refinement
to
the
dietary
water
exposure
analyses
may
be
required
as
the
risk
assessment
is
developed.
Therefore,
provided
the
final
dietary
water
exposure
assessment
includes
the
metabolite
of
toxicological
concern
and
does
not
underestimate
the
potential
risk
for
infants
and
children,
the
safety
factor
recommendations
of
this
Committee
stand.
C.
Residential
Exposure
Considerations
There
are
no
registered
residential
uses
for
tebuthiuron.
III.
RISK
CHARACTERIZATION
A.
FQPA
Safety
Factor
Recommendation
The
Committee
recommended
that
the
FQPA
Safety
factor
for
enhanced
sensitivity
to
infants
and
children
(as
required
by
FQPA)
should
be
reduced
(3x).
A.
Rationale
for
Reducing
the
FQPA
Safety
Factor
The
Committee
concluded
that
the
safety
factor
could
be
reduced
for
Tebuthiuron
because:
1.
There
is
no
indication
of
quantitative
or
qualitative
increased
susceptibility
of
rats
to
in
utero
exposure;
2.
There
is
no
indication
of
quantitative
or
qualitative
increased
susceptibility
of
rat
offspring
seen
in
the
two
generation
reproductive
toxicity
study;
3.
The
dietary
(food
and
drinking
water)
exposure
assessments
will
not
underestimate
the
potential
exposures
for
infants
and
children.
However,
the
Committee
decided
that
a
factor
is
needed
(3x)
because
of
the
data
gap
for
a
developmental
toxicity
study
in
the
rabbit.
5
C.
Application
of
the
FQPA
Safety
Factor:
Acute
Dietary
Exposure
(Females
13
50):
When
assessing
acute
dietary
exposure
to
females
13
50,
the
reduced
FQPA
safety
factor
of
3x
will
be
used.
This
is
because
there
is
a
data
gap
for
assessing
susceptibility
of
fetuses
following
in
utero
exposure
to
tebuthiuron.
Chronic
Dietary
Exposure
(General
Population):
When
assessing
chronic
dietary
exposure
to
the
general
population,
the
FQPA
safety
factor
will
be
removed
(1x).
This
is
because
there
was
no
susceptibility
identified
in
the
2
generation
rat
reproduction
study
(a
long
term
study).
| epa | 2024-06-07T20:31:42.662900 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0146-0011/content.txt"
} |
EPA-HQ-OPP-2002-0146-0013 | Supporting & Related Material | "2002-06-25T04:00:00" | null | MEMORANDUM
SUBJECT:
Tebuthiuron
Use
Closure
Memo
(PC
Code
105501)
FROM:
Michael
McDavit,
Acting
Chief
Special
Review
Branch
TO:
Margaret
Stasikowski,
Director
Health
Effects
Division
Elizabeth
Leovey,
Acting
Director
Environmental
Fate
and
Effects
Division
This
memo
serves
as
the
Tebuthiuron
Use
Closure
Memo
and
clarifies
Tebuthiuron
uses
for
the
TRED
risk
assessment.
The
SMART
meeting
for
Tebuthiuron
was
held
May
2,
2001.
The
updated
Quantitative
Usage
Analysis
(QUA)
for
Tebuthiuron,
which
is
developed
by
the
Economic
Analysis
Branch
of
the
Biological
and
Economic
Analysis
Division
is
scheduled
for
completion
on
September
9,
2001.
Attached
is
the
most
recent
version
of
the
QUA.
Tebuthiuron
is
a
relatively
nonselective,
soil
activated
herbicide
that
acts
by
inhibiting
photosynthesis.
It
is
used
to
control
broadleaf
and
woody
weeds,
grasses,
and
brush
on
terrestrial
feed
crop
sites
(pastures
and
rangeland)
primarily
in
Texas,
Oklahoma,
and
New
Mexico
and
on
terrestrial
non
food
crop
sites
including
airports/
landing
fields,
outdoor
industrial
areas,
nonagricultural
rights
of
way,
fencerows,
hedgerows,
uncultivated
areas/
soils,
and
under
paved
roads
and
sidewalks
in
areas
where
no
future
landscaping
is
planned.
Primary
uses
include
rangelands
and
near
railroads
and
other
industrial
facilities.
Single
active
ingredient
formulation
include
granular
pelleted/
tableted,
wettable
powder,
water
dispersible
granules
and
technical
grade/
solid
products.
Three
multiple
active
ingredient
formulations
(granulars)
also
are
registered.
All
formulations
may
be
applied
as
broadcast,
banded
or
spot
treatments
using
ground
equipment.
The
pelleted/
tableted
formulation
also
may
be
applied
using
aerial
equipment.
The
LUIS
report
indicates
no
limit
on
the
number
of
applications
per
season
or
crop
cycle,
but,
the
registrant
provided
information
on
the
normal
maximum
and
typical
application
use
rates
of
Tebuthiuron
at
the
SMART
meeting.
The
attached
tables
reflect
the
use
information
(note:
"NS"
not
specified)
reflecting
labeling
current
as
of
02/
21/
2001
in
the
LUIS
report
and
the
registrants'
use
information.
The
risk
assessment
for
Tebuthiuron
will
be
based
on
the
use
sites
listed
in
the
LUIS
report.
Based
on
our
understanding,
this
information
will
allow
EFED
to
submit
it's
draft
TRED
chapter
to
SRRD
on
December
1,
2001,
and
HED
to
submit
it's
draft
TRED
chapter
to
SRRD
on
February
22,
2002,
as
it
is
currently
scheduled.
If
you
have
any
questions
or
concerns
regarding
this
memorandum,
please
contact
Wilhelmena
Livingston
at
(703)
308
8025.
cc:
Paula
Deschamp
Virginia
Dobozy
Sheila
Piper
Ken
Dockter
Kevin
Costello
Mark
Corbin
Steve
Smearman
Dan
Rosenblatt
Range
and
Pasture
Typical
vs.
Maximum
Use
Rates
Use
Site
and
Product
Name
Application
Method
and
Equipment
Registrant
Maximum
Application
Per
Use
Rate
Reflecting
Label
Maximum
Application
Per
Use
Registrant
Typical
Use
Rate
Reflecting
Label
Typical
Use
Rate
Range
and
Pasture
Oak
Desert
Species
Sand
Shinnery
Spike
20P
(20%
pellet)
Broadcast
and
spot
treatment
Applied
by
hand
using
canister
delivery,
ground
and
aerial
application
For
vulnerable
sites,
maximum
application
rate
is
dependent
upon
annual
precipitation:
°
<20"
in
annual
precipitation:
no
more
than
1
lb
a.
i./
acre
once
every
3
years
°
>20"
in
annual
precipitation:
no
more
than
2
lbs
a.
i./
acre
once
every
3
years
For
non
vulnerable
sites,
maximum
application
rate
is
dependent
upon
annual
precipitation:
°
<20"
in
annual
precipitation
no
more
than
2
lbs
once
every
3
years
and
no
more
than
two
treatments
totaling
6
lbs
a.
i./
acre
in
any
6
year
period
°
>20"
in
annual
precipitation:
on
more
than
4
lbs
a.
i./
acre
once
every
3
years
and
no
more
than
two
treatments
totaling
6
lbs
a.
i./
acre
in
any
6
year
period
4
lbs
a.
i./
acre/
NS
for
broadcast
treatment
4
lbs
a.
i./
acre/
yr
for
spot
treatment
Typical
application
is
once
every
10
20
years
1.0
1.4
lbs
for
oak
use
1.5
lbs
for
desert
species
0.3
0.5
lbs
for
sand
shinnery
NS
Industrial
Vegetation
Management
Typical
vs.
Maximum
Use
Rates
Use
Site
and
Product
Name
Application
Method
and
Equipment
Registrant
Maximum
Application
Per
Use
Rate
Reflecting
Label
Maximum
Application
Per
Use
Registrant
Typical
Use
Rate
Reflectin
g
Label
Typical
Use
Rate
Industrial
Vegetation
Management
Non
Cropland
Railroad
Industrial
General
Woody
Plant
Spike
80DF
(80%
dry
flowable)
Broadcast/
Ban
ded
and
spot
Applied
by
backpack
sprayer,
handgun
sprayer,
and
groundboom
sprayer
For
vulnerable
sites,
maximum
application
rate
is
dependent
upon
annual
precipitation:
°
<20"
in
annual
precipitation
for
broadcast/
banded
and
spot
application:
no
more
than
1
lb
a.
i./
acreonce
every
3
years
°>
20"
in
annual
precipitation
for
broadcast/
banded
and
spot
application
no
more
than
2
lb
a.
i./
acreonce
every
3
years
For
non
vulnerable
sites,
maximum
application
rate
is
dependent
upon
annual
°
<20"
and
>20"
in
annual
precipitation
for
broadcast/
banded
application
for
vegetation
control:
no
more
than
4
lbs
a.
i./
acre
once
every
3
years
and
no
more
than
two
treatments
totaling
6
lbs.
a.
i./
acre
in
any
6
year
period;
for
total
vegetation
control
and
maintenance
of
bare
ground
(ground
broadcast
only)
applied
only
once
per
year,
however
no
more
than
6
lbs
a.
i./
acre
may
be
applied
in
any
3
year
period.
°
<20"
and
>20"
in
annual
precipitation
for
spot
application
no
more
than
6
lb
a.
i./
acre
once
every
three
years
Maximum
application
rate
is
6
8
lbs/
acre,
depending
on
the
use
site
Typically
applied
to
railroad
and
industrial
annually
for
2
3
years
followed
by
rotation
to
other
products
Typically
applied
to
general
woody
plant
once
every
3
8
years
1.6
2.4
lbs
for
railroad
use
1.6
2.4
lbs
for
industrial
use
3
4
lbs
for
general
woody
plant
use
NS
| epa | 2024-06-07T20:31:42.667128 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0146-0013/content.txt"
} |
EPA-HQ-OPP-2002-0146-0014 | Supporting & Related Material | "2002-06-25T04:00:00" | null | epa | 2024-06-07T20:31:42.669559 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0146-0014/content.txt"
} |
|
EPA-HQ-OPP-2002-0146-0015 | Supporting & Related Material | "2002-08-27T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
July
5,
2002
CERTIFIED
MAIL
Dear
Registrant:
This
is
to
inform
you
that
on
July
5,
2002,
the
Environmental
Protection
Agency
(hereafter
referred
to
as
EPA
or
the
Agency)
completed
its
"Report
of
FQPA
Tolerance
Reassessment
Progress
and
Interim
Risk
Management
Decision
(TRED)
for
Tebuthiuron".
A
Notice
of
Availability,
soliciting
public
comment
for
a
30
day
period,
will
be
published
in
the
Federal
Register
(FR)
Notice
shortly.
FFDCA,
as
amended,
requires
EPA
to
reassess
all
the
tolerances
for
registered
chemicals
in
effect
on
or
before
the
date
of
the
enactment
of
the
Food
Quality
Protection
Act
(FQPA)
in
August
of
1996
against
the
new
safety
standard
adopted
in
the
FQPA.
In
reassessing
these
tolerances,
the
Agency
must
consider,
among
other
things,
aggregate
risks
from
non
occupational
sources
of
pesticide
exposure,
whether
there
is
increased
susceptibility
to
infants
and
children,
and
the
cumulative
effects
of
pesticides
with
a
common
mechanism
of
toxicity.
The
tolerances
are
considered
reassessed
once
the
safety
finding
has
been
made
or
a
modification
or
revocation
occurs.
A
reregistration
eligibility
decision
(RED)
for
Tebuthiuron,
was
completed
in
April
1994,
prior
to
FQPA
enactment.
Therefore,
it
needed
to
be
updated
to
reassess
the
tolerances
under
the
FQPA
standard.
The
Agency
has
evaluated
the
dietary
risk
associated
with
Tebuthiuron
and
has
determined
that
there
is
a
reasonable
certainty
that
no
harm
to
any
population
subgroup
will
result
from
exposure
to
Tebuthiuron
when
considering
dietary
exposure
and
all
other
non
occupational
sources
of
pesticide
exposure
for
which
there
is
reliable
information.
Therefore,
no
mitigation
measures
are
needed,
and
the
tolerances
established
for
residues
of
Tebuthiuron
in/
on
raw
agricultural
commodities
are
now
considered
reassessed
as
safe
under
section
408(
q)
of
the
FFDCA.
FQPA
requires
that
EPA
consider
"available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"other
substances
that
have
a
common
mechanism
of
toxicity."
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
lowlevel
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect,
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
EPA
did
not
perform
a
cumulative
risk
assessment
as
part
of
this
reregistration
review
of
Tebuthiuron,
because
the
Agency
has
not
determined
if
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
Tebuthiuron.
If
EPA
identifies
other
substances
that
share
a
common
mechanism
of
toxicity
with
Tebuthiuron,
then
a
cumulative
risk
assessment
will
be
conducted
that
includes
Tebuthiuron
once
the
final
framework
EPA
will
use
for
conducting
cumulative
risk
assessments
is
available.
The
Agency's
human
health
findings
for
the
pesticide
Tebuthiuron,
were
discussed
in
a
closure
conference
call,
and
are
summarized
in
the
attached
chemical
overview
of
the
risk
assessments.
These
risk
assessments
and
other
documents
pertaining
to
the
Tebuthiuron
tolerance
reassessment
decision
are
listed
at
the
end
of
this
document
and
are
available
on
the
Internet
at
http://
www.
epa.
gov/
pesticides/
reregistration/
status.
htm
and
the
public
docket
for
viewing.
Tolerances
for
residues
of
tebuthiuron
are
related
to
the
consumption
of
secondary
residues
in
meat
and
milk
from
livestock
fed
tebuthiuron
treated
grass
forage
and
hay.
The
registered
uses
of
tebuthiuron
are
classified
in
40
CFR§
180.390.
The
40
CFR
tolerance
expression
under
40
CFR§
180.390
must
be
modified
as
follows:
CFR§
180.390
Tebuthiuron;
tolerances
for
residues
(a)
Tolerances
are
established
for
the
combined
residues
of
the
herbicide
tebuthiuron
(N[
5(
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl
N,
N'
dimethylurea)
and
its
metabolites
N[
5(
2
hydroxy
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N,
N'dimethylurea
–[
5(
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N
methylurea,
and
N
5(
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N'
hydroxymethyl
N
methylurea
in
or
on
the
following
agricultural
commodities:
Grass,
hay
Grass,
forage
(b)
Tolerances
are
established
for
the
combined
residues
of
the
herbicide
tebuthiuron
(N[
5(
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl
N,
N'
dimethylurea)
and
its
metabolites
N[
5(
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N
methylurea,
–[
5
(1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
urea,
2
dimethylethyl
5
amino
1,
3,
4thiadiazole
and
N[
5(
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N'
hydroxymethylN
methylurea
in
or
on
the
following
raw
agricultural
commodities:
Cattle,
fat
Cattle,
mbyp
Cattle,
meat
Goats,
fat
Goats,
mbyp
Goats,
fat
Horses,
fat
Horses,
mbyp
Horses,
meat
Sheep,
fat
Sheep,
mbyp
Sheep,
meat
(c)
A
tolerance
is
established
for
the
combined
residues
of
the
herbicide
tebuthiuron
(N[
5(
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl
N,
N'
dimethylurea)
and
its
metabolites
N[
5(
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N
methylurea,
N[
5
2
hydroxy
1,
1
dimethylethyl)
1,
3,
4
thiadiazol
2
yl]
N
methylurea,
N[
5(
1,
1dimethylethyl
1,
3,
4
thiadiazol
2
yl]
urea,
N[
5(
1,
1
dimethylethyl)
1,
3,
4thiadiazol
2
yl]
N'
hydroxymethyl
N
dimethylurea,
and
N[
5(
2
hydroxy
1,
1dimethylethyl
1,
3,
4
thiadiazol
2
yl]
N'
hydroxymethyl
N
methylurea
in
or
on
the
following
raw
agricultural
commodity:
Milk
The
Codex
Commission
has
established
that
there
are
no
maximum
residue
limits
(MRLs)
for
residues
of
tebuthiuron
in/
on
various
raw
agricultural
and
processed
commodities.
Therefore,
issues
of
compatibility
with
respect
to
U.
S.
tolerances
and
Codex
MRLs
do
not
exist.
Tebuthiuron
Tolerances
Commodity
Current
Tolerance
(ppm)
Reassessed
Tolerance
(ppm)
Tolerance
Reassessment
Cattle,
Fat
2
1
Lowered
Cattle,
MBYP
2
5
Raised
Cattle,
Meat
2
1
Lowered
Goats,
Fat
2
1
Lowered
Goats,
MBYP
2
5
Raised
Goats,
Meat
2
1
Lowered
Grasses,
Forage
20
10
Lowered
Grasses,
Hay
20
10
Lowered
Horses,
Fat
2
1
Lowered
Horses,
MBYP
2
5
Raised
Horses,
Meat
2
1
Lowered
Milk
0.
3
0.
8
Raised
Sheep,
Fat
2
1
Lowered
Sheep,
MBYP
2
5
Raised
Sheep,
Meat
2
1
Lowered
A
generic
Data
Call
In
(DCI)
that
outlines
further
data
requirements
for
this
chemical
will
be
prepared
and
mailed
to
you
in
the
near
future.
If
you
have
questions
on
this
document,
please
contact
the
Chemical
Review
Manager,
Wilhelmena
Livingston,
at
(703)
308
8025.
Lois
A.
Rossi,
Director
Special
Review
and
Reregistration
Attachments:
TRED
for
Tebuthiuron
Addendum
to
TRED
Drinking
Water
Assessment
for
Tebuthiuron
Product
Chemistry
Chapter
for
the
TRED
Residue
Chemistry
Chapter
for
the
TRED
Acute
and
Chronic
Dietary
Exposure
Assessment
for
the
TRED
Toxicology
Chapter
for
the
TRED
Third
Report
of
the
HIARC
Committee
Report
of
the
FQPA
Safety
Factor
Committee
The
Outcome
of
the
HED
MARC
Meeting
| epa | 2024-06-07T20:31:42.671291 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0146-0015/content.txt"
} |
EPA-HQ-OPP-2002-0159-0002 | Supporting & Related Material | "2002-07-12T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
February
7,
2002
SUBJECT:
Chronic
and
Cancer
Dietary
Exposure
Assessments
for
the
Tolerance
Reassessment
Decision
Document
(TRED)
for
Pronamide;
PC
code
[101701];
DP
Barcode
[D280422].
FROM:
Dave
Soderberg,
Chemist
Jose
Morales,
Chemist
Steve
Knizner,
Branch
Chief
RRB3,
Health
Effects
Division
(HED)
(7509C)
THROUGH:
Catherine
Eiden,
Branch
Senior
Scientist
RRB3,
Health
Effects
Division
(7509C)
And
Christina
Swartz,
Chemist
David
Hrdy,
Biologist
Dietary
Exposure
Science
Advisory
Council
(DESAC)
Health
Effects
Division
(7509C)
And
Chemistry
Science
Advisory
Council
(Chem
SAC)
Health
Effects
Division
(7509C)
TO:
Gary
Bangs,
Industrial
Hygienist
RRB3
Health
Effects
Division
(7509C)
And
Cecelia
R.
Watson,
Chemical
Review
Manager
Special
Review
and
Reregistration
Division
(7508C)
1
cPAD
=
chronic
Population
Adjusted
Dose
=
Chronic
RfD
FQPA
Safety
Factor
1
EPA
Reviewers:
Dave
Soderberg,
Jose
Morales,
Steve
Knizner;
Date:
17
Jan,
2002
STUDY
TYPE:
Chronic
and
Cancer
Dietary
Exposure
Assessments
for
the
Tolerance
Reassessment
Decision
Document
(TRED)
for
Pronamide
SYNONYMS:
Propyzamide
[3,
5
dichloro
N(
1,1
dimethyl
2
propynyl)
benzamide]
RESIDUE
OF
CONCERN:
The
nature
of
the
residue
in
plants
and
animals
is
adequately
understood.
The
residues
of
concern
are
pronamide
and
its
metabolites
containing
the
3,5
dichlorobenzoyl
moiety.
Executive
Summary
A
chronic
and
cancer
dietary
exposure
assessment
was
requested
to
support
the
Tolerance
Reassessment
Eligibility
Document
(TRED)
for
Pronamide.
In
response,
a
refined
tier
3
chronic/
cancer
dietary
exposure
assessment
was
conducted
for
all
supported
food
uses
(i.
e,
all
currently
registered
and
proposed
uses).
Although
tolerance
level
residues
were
used
for
some
newly
registered
crops,
the
assessment
was
based
primarily
upon
residue
monitoring
data
for
fruits
and
vegetables
and
upon
calculation
of
anticipated
residues
for
meat,
milk,
poultry
and
eggs,
and
is
the
most
refined
to
date
for
pronamide.
We
note
that
these
data
consisted
almost
entirely
of
non
detectable
residues.
Estimates
of
percent
crop
treated
(%
CT)
generated
by
the
Biological
and
Economic
Assessment
Division
(BEAD)
were
used
to
further
refine
this
assessment.
This
assessment
showed
that
the
chronic
risk
estimates
are
below
the
Agency's
level
of
concern
(<
100%
cPAD
1
)
for
the
general
U.
S.
population
and
for
all
population
subgroups.
The
chronic
dietary
exposure
estimates
for
the
two
most
highly
exposed
population
subgroups,
children
1
6
and
seniors,
are
both
estimated
at
0.000005
mg/
kg/
day
(<
1%
cPAD).
The
cancer
dietary
risk
estimate
is
1.06
x
10
7
for
the
U.
S.
population,
and
is
below
the
level
that
HED
generally
considers
to
be
of
concern
(1.0
x
10
6
).
I.
Introduction
This
memorandum
provides
the
results
of
the
dietary
exposure
assessment
for
the
general
U.
S.
population
and
various
population
subgroups
to
residues
of
pronamide
and
its
metabolites
containing
the
3,5
dichlorobenzoyl
moiety.
Risk
estimates
were
generated
for
chronic
longterm
and
cancer
dietary
exposure
using
the
most
recent
version
of
the
Dietary
Exposure
Evaluation
Model
(DEEM™,
Version
7.75),
and
using
toxicological
doses
and
endpoints
2
selected
by
the
HED
Hazard
Identification
Assessment
Review
Committee
(HIARC).
The
committee
concluded
that
toxicological
effects
were
not
expected
after
a
single
dietary
dose
and
so
did
not
select
an
acute
dietary
endpoint
for
pronamide.
This
assessment
is
the
first
dietary
exposure
analysis
that
has
been
conducted
for
pronamide
under
the
Food
Quality
Protection
Act
(FQPA).
A
previous
dietary
assessment
was
a
Dietary
Risk
Evaluation
System
(DRES)
analysis
reported
by
M.
Metzger,
Feb
19,
1994.
For
a
general
introduction
to
dietary
exposure
assessments
references
are
available
on
the
EPA/
pesticides
web
site.
See,
for
instance:
"Available
Information
on
Assessing
Exposure
from
Pesticides,
A
User's
Guide",
6/
21/
2000,
web
link:
http://
www.
epa.
gov/
fedrgstr/
EPA
PEST/
2000/
July/
Day
12/
6061.
pdf
;
or
see
HED
SOP
99.6,
8/
20/
99.
II.
Toxicological
Information
On
November
6,
2001,
the
Health
Effects
Division
(HED)
Hazard
Identification
Assessment
Review
Committee
(HIARC)
evaluated
the
recommendations
of
the
HED
toxicologist
for
pronamide
with
regard
to
the
acute
and
chronic
Reference
Doses
(RfDs),
and
with
regard
to
the
toxicological
endpoint
selection
for
occupational/
residential
exposure
assessments.
The
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
pronamide
was
also
evaluated
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996.
On
December
3,
2001,
the
FQPA
Safety
Factor
Committee
met
to
evaluate
both
the
hazard
and
exposure
databases
for
pronamide.
The
Safety
Factor
Committee
recommended
that
the
10x
FQPA
Safety
Factor
for
pronamide
be
reduced
to
3x.
A
summary
of
the
doses
and
endpoints
relevant
to
dietary
exposure
assessment
is
presented
in
Table
1.
Table
1.
Summary
of
Toxicological
Doses
and
Endpoints
for
Pronamide
for
Use
in
Dietary
Exposure
Assessment
EXPOSURE
SCENARIO
DOSE
(MG/
KG/
DAY)
ENDPOINT
STUDY
Acute
Dietary
females
(13
50)
and
general
population
including
infants
and
children
No
appropriate
endpoint
was
available
to
quantitate
risk
to
the
general
population
from
a
singledose
administration
of
pronamide.
The
developmental
effect,
abortion,
was
not
considered
to
occur
after
a
single
dose
in
this
instance
because
they
were
observed
in
rabbits
during
the
post
dosing
phase
of
the
study
(days
22
24).
Therefore,
no
endpoint
was
chosen
to
quantitate
risk
to
females
13
50
from
a
single
dose
administration
of
pronamide.
Chronic
Dietary
(all
populations)
NOAEL
=
8.46
Increased
relative
(to
body)
liver
weight
and
non
neoplastic
histologic
changes
in
the
liver,
thyroid,
and
ovaries.
Combined
Chronic
Toxicity/
Carcinogenicity
Study
Rat
UF
=
100
FQPA
SF
=
3
Chronic
RfD
=
0.08
mg/
kg/
day
Chronic
PAD
=
0.03mg/
kg/
day
3
Cancer
Q1*
=
2.59
x
10
2
(mg/
kg/
day)
1
Group
B2
chemical
"Probable
human
carcinogen"
based
on
thyroid
follicular
cell
adenomas
(males
and
females)
and
benign
interstitial
cell
tumors
(males)
in
rats
and
hepatocellular
carcinomas
in
male
mice.
Combined
Chronic
Toxicity/
Carcinogenicity
Study
Rat
III.
Residue
Information
Pronamide/
propyzamide
[3,
5
dichloro
n(
1,1
dimethyl
2
propynyl)
benzamide]
tolerances
are
established
under
40
CFR
§180.317(
a),
(b),
and
(c).
The
tolerance
expression,
listed
in
(a)
and
(c),
is
in
terms
of
"the
combined
residues
of
the
herbicide
propyzamide
and
its
metabolites
(containing
the
3,5
dichlorobenzoyl
moiety
and
calculated
as
3,5
dichloro
N(
1,1
dimethyl
2
propynyl)
benzamide)."
The
tolerance
expression,
listed
in
(b),
is
in
terms
of
the
parent
only.
Pronamide
tolerances
listed
in
40
CFR
§180.317(
a)
range
from
0.02
ppm
(for
certain
animal
commodities)
to
10.0
ppm
(for
a
non
grass
animal
feeds
group).
The
time
limited
tolerances
listed
in
40
CFR
§180.317(
b),
with
an
expiration
date
of
12/
31/
01,
are
for
Section
18
emergency
exemptions
for
pronamide
uses
on
cranberries
(0.05
ppm)
and
grasses
(forage
1.0
ppm
and
hay
0.5
ppm).
The
tolerances
listed
in
40
CFR
§180.317(
c)
are
for
regional
registrations
of
pronamide
on
dried
(winter)
peas
(0.05
ppm)
and
rhubarb
(0.1
ppm).
Adequate
enforcement
methods
are
available
for
the
determination
of
residues
in/
on
plant
and
animal
commodities.
Updates
to
the
tolerances
that
are
used
in
this
document
are
taken
from
proposed
reassessments
of
tolerances
reported
in
the
residue
chemistry
chapter
of
the
TRED
(J.
Morales,
in
process).
Pronamide
is
a
systemic
herbicide.
Residues
are
translocated
into
the
plant
through
the
roots.
Pronamide
and
its
metabolites
containing
the
3,5
dichlorobenzoyl
moiety
are
the
residues
of
concern.
Although
pronamide
is
a
large
part
of
the
total
residue
of
interest,
significant
amounts
of
metabolites
containing
the
3,5
dichlorobenzoyl
moiety
may
also
be
present.
The
residues
measured
in
field
trials
include
these
metabolites
by
incorporation
of
a
hydrolysis
step;
however,
results
of
monitoring
by
the
U.
S.
Department
of
Agriculture,
Agricultural
Marketing
Service's
Pesticide
Data
Program
(PDP)
analyses
are
also
used
in
this
assessment
for
some
crops,
and
analyses
performed
by
PDP
measured
only
the
parent
compound.
Therefore,
all
PDP
results
are
multiplied
by
a
factor
of
2
to
assure
that
residues
of
the
3,5
dichlorobenzoyl
containing
metabolites
are
conservatively
accounted
for
in
this
assessment.
[The
factor
of
2
comes
from
a
report
on
a
confined
rotational
crop
study
(L.
Cheng,
D197436,
5
May,
1994)
that
showed
residues
of
the
3,5
dichlorobenzoyl
containing
metabolites
to
be
present
in
roughly
equal
amounts
to
the
parent
up
to
97
days
after
treatment.]
Because
all
PDP
results,
but
one,
are
non
detects,
which
are
ordinarily
valued
at
½
of
the
method
limit
of
detection
(LOD),
this
means
that
the
non
detects
in
the
PDP
data
for
this
assessment
are
valued
at
the
LOD
to
account
for
the
metabolites.
Percent
Crop
Treated
and
Processing
Information:
4
The
percent
crop
treated
(%
CT)
dataset
from
OPP's
Biological
and
Economic
Assessment
Division
(BEAD)
is
provided
in
Attachment
1.
This
report
was
last
updated
on
September
26,
2001.
No
processing
information
was
used
in
this
assessment.
DEEM™
default
processing
factors
were
used
wherever
they
existed
for
processed
food
derived
from
the
relevant
crops.
However,
because
residue
data
were
available
in
the
PDP
database
for
grape
juice,
pear
juice
and
apple
juice,
these
PDP
data
were
used
directly,
i.
e,
without
DEEM
default
processing
factors,
for
grape
juice
and
grape
wine,
and
for
pear
juice
and
apple
juice.
Factors
for
the
juice
concentrates
were
estimated
from
the
ratio
of
the
DEEM
default
factors
for
juice/
juice
concentrate.
Residue
Estimates:
Crops
Apples
In
the
year
2000,
PDP
analyzed
184
samples
of
fresh
apples
and
detected
no
residues
of
pronamide
with
an
average
LOD
of
0.005
ppm.
This
result
is
also
supported
by
multi
year
FDA
testing
for
pronamide
in
apples
with
no
detectable
residues.
The
anticipated
residue
estimate
(AR)
for
apples
is
0.005
ppm.
BEAD
reported
that
1%
of
the
apple
crop
is
treated
with
pronamide.
For
apples
and
all
other
crops,
except
lettuce,
the
percent
crop
treated
value
is
applied
as
adjustment
factor
2
in
the
DEEM
TM
program.
Apple
Juice
In
1998,
PDP
tested
619
samples
of
apple
juice
for
pronamide
and
detected
no
residues.
The
average
LOD
was
0.013
ppm.
The
absence
of
residues
in
apple
juice
is
supported
by
the
absence
of
residues
in
apples.
Therefore
0.013
ppm
was
used
as
the
AR
for
apple
juice.
Because
1%
of
the
apple
crop
was
reported
to
be
treated
with
pronamide,
this
was
applied
as
adjustment
factor
2.
Since
direct
monitoring
data
were
available,
no
processing
factor
was
used
for
apple
juice
and
the
ratio
of
DEEM
default
processing
factors
of
3.9/
1.3
=
3.0
was
used
for
apple
juice
concentrate.
Apricot
A
previous
AR
memo
(L.
Cheng,
12/
15/
93,
No
DP
Barcode)
recommended
an
AR
of
0.005
ppm
(½
LOD)
for
stone
fruits
based
upon
the
then
available
FDA
data.
Because
FDA
methods
are
capable
of
measuring
parent
only,
and
to
assure
that
residues
of
3,5
dichlorobenzoyl
containing
metabolites
are
also
included,
an
AR
of
0.01
ppm,
rather
than
the
previously
proposed
0.005
ppm,
should
be
used.
FDA
has
since
tested
the
following
numbers
of
stone
fruit
samples
for
pronamide
between
1993
1999
with
the
same
lower
limit
of
reported
results.
Table
2.
Number
of
Stone
Fruit
samples
Tested
by
FDA
in
recent
Years.
No
Residues
of
Pronamide
were
detected
in
these
samples.
5
year/
crop
1993
1994
1995
1996
1997
1998
1999
apricots2828288
2
8
18
cherries
80
43
47
15
46
29
68
nectarines35454
2
6
6
4
peaches
116
189
117
75
105
114
77
plums
3
14
4
2
None
of
these
samples
contained
any
detectable
residues
of
pronamide.
As
noted
below,
under
the
specific
crops,
in
the
year
2000
PDP
tested
cherries,
nectarines
and
peaches
for
pronamide
and
all
were
non
detects.
A
weighted
average
LOD
from
these
various
samples
is
0.009
ppm.
An
AR
of
0.01
ppm
will
therefore
be
translated
to
apricots.
As
noted
under
the
peaches
topic,
cherries
and
plums
were
reported
by
BEAD
to
be
treated
at
a
rate
of
less
than
1%
of
the
crop.
Thus,
a
value
of
1
%
crop
treated
was
translated
to
all
stone
fruits.
Artichoke
A
previous
AR
memo
(L.
Cheng,
12/
15/
93,
No
DP
Barcode)
recommended
an
AR
of
0.005
ppm
based
upon
½
of
the
lower
limit
reported
in
field
trials
(which
also
include
testing
for
metabolites).
BEAD
reported
that
21%
of
artichokes
are
treated
with
pronamide.
Blackberries
A
previous
AR
memo
(L.
Cheng,
12/
15/
93,
No
DP
Barcode)
recommended
an
AR
of
0.01
ppm
for
blackberries,
blueberries,
boysenberries
and
raspberries
based
upon
field
trials.
BEAD
reported
that
6%
of
blackberries
are
treated
with
pronamide.
Blueberries
A
previous
AR
memo
(L.
Cheng,
12/
15/
93,
No
DP
Barcode)
recommended
an
AR
of
0.01
ppm
for
blackberries,
blueberries,
boysenberries
and
raspberries
based
upon
field
trials.
BEAD
reported
that
<1%
of
blackberries
are
treated
with
pronamide.
HED
practice
is
to
default
to
1%
crop
treated
when
BEAD
reports
less
than
1%
of
the
crop
is
treated.
Boysenberries
A
previous
AR
memo
(L.
Cheng,
12/
15/
93,
No
DP
Barcode)
recommended
an
AR
of
0.01
ppm
for
blackberries,
blueberries,
boysenberries
and
raspberries
based
upon
field
trials.
BEAD
reported
that
6%
of
blackberries
are
treated
with
pronamide,
and
this
value
was
translated
to
boysenberries.
Cherries
In
the
year
2000,
PDP
tested
275
samples
of
cherries
for
pronamide
and
detected
no
residues
with
an
average
LOD
of
0.0106
ppm.
This
result
is
supported
by
multi
year
testing
by
FDA
for
pronamide
in
cherries
and
other
stone
fruits,
as
described
above.
Thus,
the
AR
for
cherries
is
0.011
ppm.
BEAD
has
reported
that
less
than
1%
of
cherries
are
treated
with
pronamide,
which
is
rounded
up
to
1%
by
HED.
6
Cranberries
The
tolerance
of
0.05
ppm
was
used
for
cranberries.
No
information
was
available
on
the
percentage
of
the
crop
treated
so
it
was
assumed
that
100%
of
cranberries
are
treated
with
pronamide.
Endive
The
tolerance
of
1
ppm
was
used
for
endive.
BEAD
reported
that
31%
of
the
endive
crop
is
treated
with
pronamide.
Grapes:
In
the
year
2000,
PDP
tested
741
grape
samples
for
pronamide
and
detected
no
residues
with
an
average
LOD
of
0.013.
This
result
is
supported
by
multi
year
testing
by
FDA
for
pronamide
in
grapes
with
no
detections
of
pronamide.
This
value
is
the
AR.
BEAD
has
reported
that
<1%
of
grapes
are
treated
with
pronamide.
Grape
Juice
In
1998
1999,
PDP
analyzed
1007
samples
of
grape
juice
and
found
no
residues
of
pronamide.
This
result
is
supported
by
the
findings
of
no
detectable
residues
in
grapes.
The
average
LOD
of
these
analyses
is
0.013
ppm.
Therefore
an
AR
of
0.013
was
used
for
grape
juice,
grape
juice
concentrate
and
wine.
BEAD
reported
that
1%
of
the
grape
crop
is
treated
with
pronamide.
Since
direct
analyses
were
used,
the
DEEM
processing
factor
was
removed
for
grape
juice,
and
was
replaced
by
the
ratio
of
the
DEEM
factors
for
grape
juice
concentrate/
grape
juice
(3.6/
1.2
=
3.0)
for
grape
juice
concentrate.
Lettuce:
In
1999
2000,
PDP
analyzed
925
samples
of
fresh
lettuce
for
pronamide
(parent
only).
One
sample
contained
a
detectable
residue
at
0.012
ppm
(evaluated
here
as
0.024
ppm
to
include
metabolites).
The
average
LOD
for
this
data
set
is
0.0148
ppm.
The
average
LOD,
rather
than
½
LOD,
is
used
as
a
conservative
estimate
of
the
non
detect
level
for
all
pronamide
residues
containing
the
dichlorobenzene
ring
because
PDP
analyzed
only
for
parent
pronamide.
Lettuce
is
36%
crop
treated
in
the
assessment.
The
AR,
including
%
crop
treated,
is
0.0053
ppm.
(%
CT
cannot
be
applied
separately
for
lettuce,
because
that
would
incorrectly
change
the
one
detectable
residue.
Nectarines
In
the
year
2000,
PDP
analyzed
345
nectarines
for
pronamide
and
detected
no
residues
with
an
average
LOD
of
0.003
ppm.
This
finding
is
supported
by
multi
year
testing
of
various
stone
fruits
by
FDA
with
no
detectable
residues,
as
described
above.
As
explained
for
peaches,
the
estimate
of
1%
crop
treated
is
translated
to
nectarines.
Peaches
In
the
year
2000,
PDP
tested
536
five
pound
composite
samples
of
peaches
for
pronamide
and
detected
no
residues
with
an
average
LOD
of
0.012
ppm.
In
the
same
year
PDP
tested
532
individual
peaches
for
pronamide
and
detected
no
residues
with
an
average
LOD
of
0.012
ppm.
This
finding
is
also
supported
by
multi
year
testing
of
various
stone
fruits
by
FDA
with
no
detectable
residues,
as
described
above.
BEAD
reported
less
than
1%
crop
treated
for
cherries
and
plums,
but
did
not
report
usage
for
other
stone
fruits.
Therefore,
1%
crop
treated
is
used
for
all
stone
fruits.
Pears
In
1998
1999,
PDP
analyzed
1007
fresh
pears
for
pronamide
(parent
only).
None
of
the
samples
contained
detectable
residues.
This
finding
is
supported
by
the
absence
of
residues
in
7
PDP
testing
of
apples
and
also
by
multi
year
testing
by
FDA
with
no
detectable
residues.
The
average
LOD
for
this
data
set
is
0.011
ppm.
This
value
is
used
as
the
AR.
This
same
value
is
used
for
pear
juice
and
other
processed
pear
commodities.
PDP
also
analyzed
canned
pears
in
this
time
period,
and
also
found
no
detects
in
these
products.
The
value
of
1%
crop
treated
was
translated
from
apples.
Dried
Peas
The
tolerance
of
0.05
ppm
was
used
for
dried
peas.
BEAD
reported
that
considerably
less
than
1%
of
peas
are
treated
with
pronamide.
Dried
peas
were
presumed
to
be
subsumed
within
this
value,
and
since
the
reported
value
was
below
0.1%
crop
treated
for
all
peas,
it
was
reasonable
to
use
1%
crop
treated
for
dried
peas.
Plums
As
discussed
under
apricots,
an
AR
of
0.01
ppm
and
1%
crop
treated
is
also
used
for
plums.
Radicchio
The
tolerance
of
2
ppm
was
used
for
radicchio.
No
information
was
available
on
the
percent
of
radicchio
treated
with
pronamide,
therefore,
100%
of
the
crop
was
assumed
to
be
treated.
Raspberries
A
previous
AR
memo
(L.
Cheng,
12/
15/
93,
No
DP
Barcode)
recommended
an
AR
of
0.01
ppm
for
blackberries,
blueberries,
boysenberries
and
raspberries
based
upon
field
trials.
BEAD
reported
that
5%
of
raspberries
are
treated
with
pronamide.
Rhubarb
A
previous
AR
memo
(L.
Cheng,
12/
15/
93,
No
DP
Barcode)
recommended
an
AR
of
0.039
ppm
for
rhubarb
based
upon
field
trials.
BEAD
did
not
report
what
percent
of
rhubarb
is
treated
with
pronamide.
In
such
cases
HED
practice
is
to
default
to
100%
crop
treated.
Animal
Products
Chronic
Anticipated
Residues
Meat/
Milk/
Poultry/
Eggs
Feedstuffs
Anticipated
residues
for
meat
and
milk
were
calculated
using
a
dairy
cattle
feeding
study
and
field
trial
data
for
residues
of
pronamide
in/
on
alfalfa,
plus
percent
of
crop
treated
information
(A.
Halverson,
9/
26/
01).
The
field
trial
data
used
to
calculate
the
AR
for
alfalfa
hay
and
meal
were
presented
in
a
previous
memo
(L.
Cheng,
12/
17/
93).
Briefly,
alfalfa
seed,
hay
and
meal
were
the
major
feed
items
for
cattle
and
poultry.
An
anticipated
residue
(4.8
ppm)
in
alfalfa
hay
was
calculated
based
on
field
data
obtained
from
trials
conducted
in
CA,
ID,
MN,
WA
(West
of
the
Mississippi
River),
MS,
NJ,
NY,
and
PA
(East
of
the
Mississippi
River).
Alfalfa
seed
and
meal
were
assumed
to
contain
similar
levels
of
pronamide
residues.
Because
chronic
ARs
were
being
calculated,
the
alfalfa
anticipated
residue
level
for
dietary
burden
calculations
was
adjusted
by
the
percent
of
crop
treated
data.
The
estimated
maximum
percent
crop
treated
from
BEAD
for
alfalfa
is
0.2%
and
the
average
is
0.1%.
These
estimates
are
far
below
the
usual
HED
default
of
1%,
so
HED
considered
using
these
actual
estimates
to
avoid
overestimating
pronamide
residues
in
the
large
consumption
items:
meat,
milk,
poultry
and
eggs.
To
assure
this
would
be
correct,
HED
consulted
BEAD
about
the
expected
reliability
of
these
8
estimated
values.
For
safety,
BEAD
recommended
using
a
more
conservative
estimate
of
0.5%
(electronic
communication,
A.
Halverson
to
D.
Soderberg,
6
February
2002),
and
the
ARs
were
calculated
using
this
value
of
0.5%.
Meat
and
Fat
Two
groups
of
cattle
were
fed
alfalfa
hay
containing
20
or
40
ppm
field
aged
pronamide
residues
for
three
weeks.
Residues
in
tissues
are
listed
in
Table
3.
Table
3.
Pronamide
Residues
in
Meat
and
Fat.
Sample
Dose
Level
(ppm)
Residues
(ppm)
Number
of
Samples
Average
Residue
(ppm)
after
feeding
at
20
ppm
Kidney
20
40
0.05
0.31
0.66
1.18
2
2
0.18
Liver
20
40
0.23
0.55
0.92
1.48
2
2
0.39
Diaphragm
muscle
20
40
<0.01
0.02
0.05
0.06
2
2
0.015
Front
leg
muscle
20
40
<0.01
0.02
0.03
0.05
2
2
0.015
Hind
leg
muscle
20
40
<0.01
0.02
0.03
0.06
2
2
0.015
Mesentery
fat
20
40
0.02
0.08
0.21
0.48
2
2
0.05
Thoracic
fat
20
40
<0.01
0.09
0.18
0.34
2
2
0.05
Kidney
fat
20
40
0.02
0.10
0.25
0.47
2
2
0.06
Assuming
40%
alfalfa
hay
(89%
dry
matter)
and
10%
alfalfa
meal
(89%
dry
matter)
in
the
cattle
diet,
with
an
AR
in
both
of
4.8
ppm
and
0.5%
crop
treated,
the
anticipated
dietary
burden
is
4.8
x
0.50/
0.89
x
0.005
=
0.013
ppm.
Using
the
results
obtained
from
the
20
ppm
feeding
level,
the
following
ARs
are
estimated:
muscle,
0.015/
20
x
.013
=
1
x
10
5
ppm;
fat,
4
x
10
5
ppm;
liver,
2.5
x
10
4
ppm;
and
kidney,
1.2
x
10
4
ppm.
Milk
Rohm
and
Haas
has
submitted
a
feeding
study
in
which
12
lactating
Holstein
and
Guernsey
cows
were
fed
alfalfa
hay
containing
pronamide
residues
at
3
dosage
levels
for
varying
9
periods
of
time.
The
dosage
levels
were
1.8
ppm
for
16
30
days;
7.5
ppm
for
16
30
days;
or
0.7
ppm
for
21
days
followed
by
3.5
ppm
for
16
30
days.
Milk
was
collected
twice
daily
and
pooled
for
residue
analysis.
Results
are
summarized
in
Table
4.
Table
4.
Pronamide
Residues
in
Milk.
Sample
Feeding
Level,
ppm
Residues,
ppm
Number
of
Samples
Range
Average
Milk
0.7
<0.005
<0.005
33
1.8
<0.005
0.007
<0.005
37
3.5
<0.005
0.01
0.005
38
7.5
0.
005
0.015
0.011
37
A
dairy
cattle
diet
of
50
percent
alfalfa
hay
(89%
dry
matter)
for
which
an
anticipated
residue
of
4.8
ppm
had
been
calculated,
in
conjunction
with
0.2%
crop
treated,
gives
an
anticipated
dietary
burden
of
0.013
ppm.
Based
on
the
average
residue
in
the
feeding
trial
being
non
detectable
at
the
1.8
ppm
feeding
level
and
extrapolating
from
one
half
the
limit
of
detection
(½
LOD
=
0.0025
ppm),
anticipated
residues
in
milk
are
1.8
x
10
5
ppm.
Poultry
and
eggs
Hens
in
three
groups
of
15
animals
were
fed
diets
containing
0.22,
0.51,
or
1.82
ppm
pronamide
residues
for
a
period
of
up
to
seven
weeks.
Combined
residues
of
pronamide
and
its
metabolites
were
<0.01
ppm
in
all
eggs
from
the
0.22
and
0.51
ppm
feeding
groups
(94
eggs/
group).
Eggs
(7
samples)
in
the
1.82
ppm
feeding
group
contained
<0.01
ppm
residues
for
the
first
five
days
of
dosing,
after
which
residues
in
68
subsequent
samples
contained
<0.01
0.022
ppm.
Most
samples
contained
residues
at
0.01
0.016
ppm,
and
residues
remained
fairly
stable
over
the
duration
of
the
experiment.
Combined
residues
in
gizzard,
heart,
muscle,
skin,
fat,
and
liver
were
<0.01
ppm
in
hens
dosed
at
0.22
ppm.
At
the
0.51
ppm
dose
level,
0.01
ppm
residues
were
found
in
samples
of
fat
and
gizzard
(6
samples),
and
liver.
In
hens
dosed
at
1.82
ppm,
combined
residues
were
0.01
0.03
ppm
in
gizzard,
<0.01
ppm
in
heart,
<0.01
ppm
(0.007,
0.008
ppm)
in
light
meat,
<0.01
ppm
(0.007
ppm)
in
dark
meat,
<0.01
0.03
ppm
in
fat,
and
0.02
0.04
ppm
in
liver.
The
expected
dietary
intake
of
pronamide
by
poultry
is
based
on
a
diet
of
20%
alfalfa
seed
and
5%
alfalfa
meal,
correcting
for
0.5%
crop
treated,
resulting
in
an
anticipated
dietary
burden
of
0.006
ppm.
Based
on
the
results
from
the
0.22
ppm
feeding
group
(all
non
detectable
residues)
and
using
one
half
the
limit
of
detection
(½
LOD
=
0.005
ppm),
the
AR
for
all
poultry
commodities
is
1.4
x
10
4
ppm.
Table
5.
Data
and
Residue
Estimates
Used
in
Dietary
Analyses
10
Crop
Food
Forms
Included
Source
of
Data
Processing
Factor
Percent
Crop
Treated
Anticipated
Residue
(ppm)
Apples
All
PDP
DEEM
Default
1%
0.
005
Apple
Juice
All
PDP
1%
0.
013
Apricots
All
translated
from
other
stone
fruits
DEEM
Default
1%
0.
01
Artichokes
All
previous
AR
memofield
trials
DEEM
Default
21%
0.005
Blackberries
All
previous
AR
memofield
trials
DEEM
Default
6%
0.
01
Blueberries
All
previous
AR
memofield
trials
DEEM
Default
1%
0.
01
Boysenberries
All
previous
AR
memofield
trials
DEEM
Default
6%
0.
01
Cherries
All
PDP
DEEM
Default
1%
0.
011
Cranberries
All
tolerance
DEEM
Default
100%
0.05
Endive
All
tolerance
DEEM
Default
31%
1.0
Grapes
Fresh
Grapes,
Raisins
and
Leaves
PDP
DEEM
Default
1%
0.
013
Grape
Juice
Juice,
Concentrate
and
Wine
PDP
1%
0.
013
Lettuce
All
PDP
DEEM
Default
0
0.0053
(includes
%
CT)
Nectarines
All
PDP
DEEM
Default
1%
0.
003
Peaches
All
PDP
DEEM
Default
1%
0.
012
Pears
All
PDP
DEEM
Default
1%
0.
011
Peas
(Dried)
All
tolerance
DEEM
Default
1%
0.
05
Plums
All
translated
from
other
stone
fruits
DEEM
Default
1%
0.
01
Prunes
All
translated
from
other
stone
fruits
DEEM
Default
1%
0.
01
Radicchio
All
tolerance
DEEM
Default
100%
2.0
Raspberries
All
previous
AR
memofield
trials
DEEM
Default
5%
0.
01
Rhubarb
All
previous
AR
memofield
trials
DEEM
Default
100%
0.039
Crop
Food
Forms
Included
Source
of
Data
Processing
Factor
Percent
Crop
Treated
Anticipated
Residue
(ppm)
11
Beef
Muscle
All
calculated
ARs
DEEM
Default
N/
A
0.00001
Byproducts
All
calculated
ARs
DEEM
Default
N/
A
0.00012
Liver
All
calculated
ARs
DEEM
Default
N/
A
0.00025
Kidney
All
calculated
ARs
DEEM
default
N/
A
0.00012
Beef
Fat
All
calculated
ARs
DEEM
Default
N/
A
0.00004
Other
Organ
Meat
All
calculated
ARs
DEEM
Default
N/
A
0.00012
Chicken
Muscle
All
calculated
ARs
DEEM
Default
N/
A
0.00014
Byproducts
All
calculated
ARs
DEEM
Default
N/
A
0.00014
Liver
All
calculated
ARs
DEEM
Default
N/
A
0.00014
Fat
All
calculated
ARs
DEEM
Default
N/
A
0.00014
Other
Organ
Meat
All
calculated
ARs
DEEM
Default
N/
A
0.00014
Eggs
All
calculated
ARs
DEEM
Default
N/
A
0.00014
Goat
Muscle
All
calculated
ARs
DEEM
Default
N/
A
0.00001
Byproducts
All
calculated
ARs
DEEM
Default
N/
A
0.00012
Liver
All
calculated
ARs
DEEM
Default
N/
A
0.00025
Kidney
All
calculated
ARs
DEEM
default
N/
A
0.00012
Fat
All
calculated
ARs
DEEM
Default
N/
A
0.00004
Other
Organ
Meat
All
calculated
ARs
DEEM
Default
N/
A
0.00012
Hog
Muscle
All
calculated
ARs
DEEM
Default
N/
A
0.00001
Byproducts
All
calculated
ARs
DEEM
Default
N/
A
0.00012
Liver
All
calculated
ARs
DEEM
Default
N/
A
0.00025
Kidney
All
calculated
ARs
DEEM
default
N/
A
0.00012
Fat
All
calculated
ARs
DEEM
Default
N/
A
0.00004
Other
Organ
Meat
All
calculated
ARs
DEEM
Default
N/
A
0.00012
Horse
Meat
All
calculated
ARs
DEEM
Default
N/
A
0.00001
Milk
All
calculated
ARs
DEEM
Default
N/
A
0.000018
Poultry
Muscle
All
calculated
ARs
DEEM
Default
N/
A
0.000055
Crop
Food
Forms
Included
Source
of
Data
Processing
Factor
Percent
Crop
Treated
Anticipated
Residue
(ppm)
12
Byproducts
All
calculated
ARs
DEEM
Default
N/
A
0.000055
Liver
All
calculated
ARs
DEEM
Default
N/
A
0.000055
Fat
All
calculated
ARs
DEEM
Default
N/
A
0.000055
Other
Organ
Meat
All
calculated
ARs
DEEM
Default
N/
A
0.000055
Sheep
Muscle
All
calculated
ARs
DEEM
Default
N/
A
0.00001
Byproducts
All
calculated
ARs
DEEM
Default
N/
A
0.00012
Liver
All
calculated
ARs
DEEM
Default
N/
A
0.00025
Kidney
All
calculated
ARs
DEEM
default
N/
A
0.00012
Fat
All
calculated
ARs
DEEM
Default
N/
A
0.00004
Other
Organ
Meat
All
calculated
ARs
DEEM
Default
N/
A
0.00012
Turkey
Muscle
All
calculated
ARs
DEEM
Default
N/
A
0.000055
Byproducts
All
calculated
ARs
DEEM
Default
N/
A
0.000055
Liver
All
calculated
ARs
DEEM
Default
N/
A
0.000055
Fat
All
calculated
ARs
DEEM
Default
N/
A
0.000055
Other
Organ
Meat
All
calculated
ARs
DEEM
Default
N/
A
0.000055
Veal
Muscle
All
calculated
ARs
DEEM
Default
N/
A
0.00001
Byproducts
All
calculated
ARs
DEEM
Default
N/
A
0.00012
Liver
All
calculated
ARs
DEEM
Default
N/
A
0.00025
Kidney
All
calculated
ARs
DEEM
default
N/
A
0.00012
Fat
All
calculated
ARs
DEEM
Default
N/
A
0.00004
Other
Organ
Meat
All
calculated
ARs
DEEM
Default
N/
A
0.00012
*
Ordinarily,
in
this
assessment,
the
ARs
for
the
fruit
and
vegetable
crops
are
based
entirely
upon
LODs
and
the
percent
crop
treated
is
entered
into
the
DEEM
program
separately
from
the
AR,
as
adjustment
factor
2.
However,
this
was
not
possible
for
lettuce,
because
lettuce
has
one
sample
with
detected
residues
of
pronamide.
Therefore,
for
lettuce
the
AR
includes
the
36%
crop
treated
and
adjustment
factor
2
is
set
to
a
value
of
1.
IV.
DEEM™
Program
and
Consumption
Information
13
The
chronic
and
cancer
dietary
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(DEEM™)
software
Version
7.75,
which
incorporates
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intake
by
Individuals
(CSFII),
1989
1992.
The
1989
92
data
are
based
on
the
reported
consumption
of
more
than
10,000
individuals
over
three
consecutive
days,
and
therefore
represent
more
than
30,000
unique
"person
days"
of
data.
Foods
"as
consumed"
(e.
g.,
apple
pie)
are
linked
to
raw
agricultural
commodities,
and
their
food
forms
(e.
g.,
apples
cooked/
canned
or
wheat
flour),
by
proprietary
recipe
translation
files
internal
to
the
DEEM
software.
For
chronic
and
cancer
exposure
and
risk
assessment,
an
estimate
of
the
residue
level
in
each
food
or
food
form
(e.
g.,
orange
or
orange
juice)
on
the
commodity
residue
list
is
multiplied
by
the
average
daily
consumption
estimate
for
that
food/
food
form.
The
resulting
residue
consumption
estimate
for
each
food/
food
form
is
summed
with
the
residue
consumption
estimates
for
all
other
food/
food
forms
on
the
commodity
residue
list
to
arrive
at
the
total
estimated
exposure.
Exposure
estimates
are
expressed
in
mg/
kg
body
weight/
day
and
as
a
percent
of
the
cPAD.
This
procedure
is
performed
for
each
population
subgroup.
HED
notes
that
there
is
a
degree
of
uncertainty
in
estimating
exposures
for
certain
population
subgroups
that
may
not
be
sufficiently
represented
in
the
consumption
surveys
(e.
g,
nursing
and
non
nursing
infants
or
Hispanic
females).
Therefore,
risks
estimated
for
these
population
subgroups
are
not
reported
explicitly
but
are
included
within
larger
representative
populations
(e.
g.,
all
infants
or
females,
13
50
years).
V.
Results
and
Discussion
A
refined,
tier
3,
chronic
and
cancer
dietary
exposure
assessment
for
pronamide
was
performed.
The
analysis
was
based
primarily
upon
residue
monitoring
data
for
fruits
and
vegetables
and
upon
calculated
ARs
for
meat,
milk,
poultry
and
eggs.
Field
trial
data
and
tolerance
level
residues
were
used
for
some
minor
crops.
This
assessment
is
the
most
refined
to
date
for
pronamide.
Results
for
chronic
exposure
are
shown
in
Table
6
and
in
Attachment
2.
Results
for
cancer
exposure
are
shown
in
Table
7
and
Attachment
3.
All
results
for
all
appropriate
population
subgroups
are
below
HED's
levels
of
concern.
Table
6.
Results
of
Chronic
Dietary
Exposure
Analysis
14
Population
Subgroup
cPAD
(mg/
kg/
day)
Exposure
(mg/
kg/
day)
%
cPAD
U.
S.
Population
(total)
0.
03
mg/
kg/
day
0.
000004
<1%
All
Infants
(<
1
year)
0.
03
mg/
kg/
day
0.
000002
<1%
Children
1
6
years
0.
03
mg/
kg/
day
0.
000005
<1%
Children
7
12
years
0.
03
mg/
kg/
day
0.
000004
<1%
Females
13
50
0.03
mg/
kg/
day
0.
000004
<1%
Males
13
19
0.03
mg/
kg/
day
0.
000003
<1%
Males
20+
years
0.
03
mg/
kg/
day
0.
000004
<1%
Seniors
55+
0.03
mg/
kg/
day
0.
000005
<1%
Table
7.
Results
of
Cancer
Dietary
Exposure
Analysis
Population
Subgroup
Exposure
(mg/
kg/
day)
Anticipated
Cancer
Risk
U.
S.
Population
(total)
0.
000004
1.06
X
10
7
VI.
Uncertainties
Because
the
estimated
exposure
is
well
below
the
chronic
and
cancer
levels
of
concern,
any
uncertainties
are
unlikely
to
cause
the
exposure
to
exceed
a
level
of
concern.
However,
there
are
some
conservative
assumptions
that
may
have
introduced
some
uncertainties
into
this
assessment.
Tolerance
level
residues
and
100
%
CT
were
assumed
for
cranberries
and
radicchio.
The
LOD
was
used
instead
of
½LOD
for
the
non
detects
in
the
PDP
data.
For
the
animal
product
ARs
the
maximum
percent
crop
treated
was
assumed
instead
of
the
average
percent
crop
treated.
Default
DEEM
processing
factors
were
used
for
most
processed
foods.
VII.
Conclusions
A
tier
3
chronic
and
cancer
dietary
risk
assessment
was
conducted
for
all
supported
pronamide
food
uses.
Chronic
dietary
risk
estimates
are
provided
for
the
general
U.
S.
population
and
appropriate
population
subgroups.
This
assessment
concludes
that
the
chronic
exposure
estimates
are
below
HED's
level
of
concern
(<
100%
cPAD)
for
the
general
U.
S.
population
and
all
population
subgroups.
The
chronic
dietary
exposure
estimate
for
both
of
the
two
highest
population
subgroups,
children
1
6
years
and
seniors
55+
years,
is
0.000005
mg/
kg/
day
(<
1%
of
the
cPAD)
.
The
cancer
dietary
risk
estimate
associated
with
the
use
of
pronamide
for
the
U.
S.
population
is
1.06
x10
7
,
and
is
therefore
below
the
level
(1.0
x
10
6
)
that
generally
is
of
concern
to
HED.
VIII.
List
of
Attachments
15
Attachment
1:
Quantitative
Usage
Analysis
Attachment
2:
Results
of
Chronic
Dietary
Exposure
Analysis
Attachment
3:
Results
of
Cancer
Dietary
Exposure
Analysis
Attachment
4:
Residue
Input
File
cc:
RRB3RF;
D.
Soderberg;
S.
Knizner;
C.
Eiden;
C.
Swartz;
D.
Hrdy;
M.
Sahafeyen.
16
Attachment
1.
Quantitative
Usage
Analysis
for
Pronamide/
Propyzamide
Case
Number:
82
PC
Code:
101701
Date:
September
26,
2001
Analyst:
Alan
Halvorson
Based
on
available
pesticide
usage
information
for
1991
through
2000,
total
annual
domestic
usage
of
herbicide
pronamide
(propyzamide)
is
approximately
225
thousand
pounds
active
ingredient
(a.
i.).
In
terms
of
pounds
a.
i.,
total
usage
is
allocated
mainly
to
head
lettuce
(29%),
other
lettuce
(19%),
seed
crops
(13%),
fallowland
(11%),
hay
other
than
alfalfa
(8%),
horticulture
(3%)
and
alfalfa
(3%).
Sites
with
5%
or
more
of
acreage
treated
include
lettuce
other
than
head
lettuce
(49%),
head
lettuce
(36%),
California
endive/
escarole
(31%),
artichokes
(21%),
blackberries
(6%)
and
raspberries
(5%).
Rates
per
application
and
rates
per
year
are
each
generally
less
than
2
pounds
a.
i.
per
acre
for
agricultural
sites.
States
with
significant
usage
in
terms
of
pounds
a.
i.
include
Arizona,
California,
Oregon
and
Washington.
Pronamide/
Propyzamide
Case
#:
0082
AI
#:
101701
EPA
QUANTITATIVE
USAGE
ANALYSIS
Analyst:
Alan
Halvorson
9
26
01
Acres
Acres
Treated
(000)
%
Crop
Treated
Lb
AI
Appl'd
(000)
Avg
Applic
Rates/
Acre
States
of
Most
Usage
(000)
(%
of
total
lb
ai
Site
Grown
Est
Est
Est
lb
ai/
#
appl/
lb
ai/
used
by
these
states)
Avg
Max
Avg
Max
Avg
Max
year
year
appl
Alfalfa
23,724
14.2
42.5
0.1%
0.2%
6.3
18.9
0.45
1.0
0.45
OR
KS
CA
WA
100%
Apples
513.9
2.9
8.8
1%
2%
4.1
12.3
1.41
1.0
1.41
OR
WA
NY
100%
Apricots
0*
0*
0*
0*
0*
0*
Artichokes
9.7
2.0
2.9
21%
30%
3.1
4.5
1.55
1.0
1.55
CA
100%
Berries
175.9
2.1
4.2
1%
2%
2.2
4.3
1.03
1.0
1.03
OR
WA
NY
100%
Blackberries
5.3
0.3
0.5
6%
9%
0.3
0.4
0.79
1.0
0.79
OR
100%
Blueberries
59.1
0.1
0.2
0.1%
0.4%
0.1
0.2
0.97
1.0
0.97
OR
NY
100%
Raspberries
13.9
0.7
1.1
5%
8%
0.9
1.5
1.38
1.0
1.38
OR
WA
100%
Cherries
117.6
0.2
0.6
0.2%
0.5%
0.2
0.6
1.00
1.0
1.00
MI
OR
100%
Clover,
CA
0.9
1.8
0.9
1.8
1.01
1.0
1.01
Cole
Crops
305.7
1.0
3.1
0.3%
1.0%
0.9
2.6
0.84
1.0
0.84
CA
100%
Cucumbers,
Process
71.5
0.3
1.0
0.4%
1.3%
0.3
0.9
0.94
1.2
0.78
NC
100%
Endive/
Escarole,
CA
3.3
1.0
1.3
31%
40%
0.9
1.1
0.87
1.0
0.87
Fallowland
19,334
96.1
192.2
0.5%
1.0%
24.0
48.0
0.25
1.0
0.25
WA
ID
100%
Grapes
942.7
0.2
0.7
0.02%
0.07%
0.4
1.2
1.87
1.0
1.87
PA
NC
100%
Hay,
Other(*)
34,597
17.9
53.6
0.1%
0.2%
17.0
50.9
0.95
1.0
0.95
OR
100%
Leafy
Veget,
Oth(**)
73.4
0.05
0.14
0.1%
0.2%
0.05
0.14
1.00
1.0
1.00
CA
100%
Celery
27.5
0.04
0.12
0.1%
0.4%
0.04
0.11
0.92
1.0
0.92
CA
100%
Lettuce,
Head
206.8
75.4
94.3
36%
46%
65.5
91.4
0.87
1.1
0.76
CA
AZ
99%
Lettuce,
Other
84.8
41.6
55.1
49%
65%
41.5
60.0
1.00
1.2
0.81
CA
76%
Nectarines
0*
0*
0*
0*
0*
0*
Peaches
171.0
0.3
0.9
0.2%
0.5%
0.3
0.9
1.00
1.0
1.00
WA
100%
17
Pears
70.9
2.3
5.4
3%
8%
4.1
10.0
1.76
1.0
1.76
OR
100%
Acres
Acres
Treated
(000)
%
Crop
Treated
Lb
AI
Appl'd
(000)
Avg
Applic
Rates/
Acre
States
of
Most
Usage
(000)
(%
of
total
lb
ai
Site
Grown
Est
Est
Est
lb
ai/
#
appl/
lb
ai/
used
by
these
states)
Avg
Max
Avg
Max
Avg
Max
year
year
appl
Peas,
Green
270.6
0.4
1.2
0.1%
0.4%
0.4
1.3
1.09
1.0
1.09
MN
100%
Peppers
68.1
0.2
0.6
0.3%
0.8%
1.0
Plums/
Prunes
0*
0*
0*
0*
0*
0*
Rhubarb
Roots/
Tubers(#)
235.8
3.3
6.5
1%
3%
2.9
5.8
0.89
1.0
0.89
CA
100%
Seed
Crops
1,382.7
42.2
63.3
3%
5%
28.1
42.2
0.67
1.0
0.67
OR
98%
Sugar
Beets
1,454.4
4.5
13.5
0.3%
0.9%
3.6
10.8
0.80
1.0
0.80
OR
100%
Woodland
60,478
5.0
25.2
0.01%
0.04%
0.6
2.8
0.11
1.0
0.11
NC
100%
Golf
Courses
5.1
10.3
CA
FL
OK
SC
GA
AL
93%
Horticultural
5.9
11.9
FL
North
Central
100%
Landscape
Maint,
CA
1.5
3.1
Lawn
Care
Operators
0.4
0.8
Ornamental
Turf,
CA
1.0
2.1
Rights
of
Way,
CA
0.1
0.2
Turf
Farms
1.9
3.8
Total
223.4
314.1
(*)
Other
than
alfalfa
(**)
Other
than
lettuce
(#)
Beets,
carrots,
horseradish,
parsnips,
radish,
rutabagas,
sweet
potatoes,
turnips
and
yams.
NOTES
ON
TABLE
DATA
A
dash()
indicates
that
information
is
not
readily
available
or
is
not
applicable.
A
"0*"
indicates
that
available
EPA
sources
show
no
observed
usage
for
this
site,
which
implies
that
there
is
little
or
no
usage.
Allocation
of
usage
among
states
includes
only
states
covered
in
corresponding
data
sources.
Calculations
of
the
above
numbers
may
not
appear
to
agree
with
each
other
because
they
are
displayed
as
rounded.
Reported
usage
estimates
above
may
include
usage
due
to
Section
18s,
misuse,
errors,
etc.
Usage
data
cover
1992
2000
for
agriculture
and
1991
1999
for
non
agriculture.
CROP/
SITE
GROUPS
AND
DEFINITIONS
Sites
that
reference
California
give
usage
only
for
California,
not
for
the
total
U.
S.
Sub
categories
under
a
crop
group
are
not
exhaustive.
DATA
SOURCES
CA
EPA,
Summary
of
Pesticide
Use
Report
Data,
1997,
1998
&
1999.
Garber
&
Hudson,
Pest
Management
in
the
United
States
Greenhouse
and
Nursery
Industry,
1993
data.
NCFAP,
National
Use
Pesticide
Database,
circa
1992
&
circa
1997.
18
US
EPA,
proprietary
data,
1991
1994
&
1996
2000.
USDA/
NASS,
Agricultural
Chemical
Usage
Fruits
Summary,
1993
&
1997.
Vegetables
Summary,
1996,
1998
&
2000
19
Attachment
2.
Results
of
Chronic
Dietary
Exposure
Analysis
U.
S.
Environmental
Protection
Agency
Ver.
7.73
DEEM
Chronic
analysis
for
PRONAMIDE
(1989
92
data)
Residue
file
name:
D:\
pronamidefeb6b.
RS7
Adjustment
factor
#2
used.
Analysis
Date
02
07
2002/
08:
47:
49
Residue
file
dated:
02
06
2002/
17:
53:
38/
8
Reference
dose
(RfD,
Chronic)
=
.03
mg/
kg
bw/
day
COMMENT
1:
contains
PDP
data
from
2000
===============================================================================
Total
exposure
by
population
subgroup
Total
Exposure
Population
mg/
kg
Percent
of
Subgroup
body
wt/
day
Rfd
U.
S.
Population
(total)
0.000004
0.0%
U.
S.
Population
(spring
season)
0.000005
0.0%
U.
S.
Population
(summer
season)
0.000003
0.0%
U.
S.
Population
(autumn
season)
0.000004
0.0%
U.
S.
Population
(winter
season)
0.000005
0.0%
Northeast
region
0.000005
0.0%
Midwest
region
0.000003
0.0%
Southern
region
0.000003
0.0%
Western
region
0.000006
0.0%
Hispanics
0.000005
0.0%
Non
hispanic
whites
0.000004
0.0%
Non
hispanic
blacks
0.000002
0.0%
Non
hisp/
non
white/
non
black
0.000005
0.0%
All
infants
(<
1
year)
0.000002
0.0%
20
Nursing
infants
0.000001
0.0%
Non
nursing
infants
0.000003
0.0%
Children
1
6
yrs
0.000005
0.0%
Children
7
12
yrs
0.000004
0.0%
Females
13
19
(not
preg
or
nursing)
0.000002
0.0%
Females
20+
(not
preg
or
nursing)
0.000004
0.0%
Females
13
50
yrs
0.000004
0.0%
Females
13+
(preg/
not
nursing)
0.000003
0.0%
Females
13+
(nursing)
0.000004
0.0%
Males
13
19
yrs
0.000003
0.0%
Males
20+
yrs
0.000004
0.0%
Seniors
55+
0.000005
0.0%
Pacific
Region
0.000007
0.0%
21
Attachment
3.
Results
of
Cancer
Dietary
Exposure
Analysis
U.
S.
Environmental
Protection
Agency
Ver.
7.73
DEEM
Chronic
analysis
for
PRONAMIDE
(1989
92
data)
Residue
file
name:
D:\
pronamidefeb6b.
RS7
Adjustment
factor
#2
used.
Analysis
Date
02
07
2002/
08:
48:
48
Residue
file
dated:
02
06
2002/
17:
53:
38/
8
Q*
=
0.0259
COMMENT
1:
contains
PDP
data
from
2000
===============================================================================
Total
exposure
by
population
subgroup
Total
Exposure
Population
mg/
kg
Lifetime
risk
Subgroup
body
wt/
day
(Q*=
.0259)
U.
S.
Population
(total)
0.000004
1.06E
07
22
Attachment
4:
Residue
Input
File
U.
S.
Environmental
Protection
Agency
Ver.
7.73
DEEM
Chronic
analysis
for
PRONAMIDE
1989
92
data
Residue
file:
D:\
pronamidefeb6b.
RS7
Adjust.
#2
used
Analysis
Date
02
07
2002
Residue
file
dated:
02
06
2002/
17:
53:
38/
8
Reference
dose
(RfD)
=
0.03
mg/
kg
bw/
day
Comment:
contains
PDP
data
from
2000
Food
Crop
RESIDUE
Adj.
Factors
Comment
Code
Grp
Food
Name
(ppm)
#1
#2
1
13A
Blackberries
0.010000
1.000
0.060
AR
mem
Full
comment:
AR
memo
field
trials
2
13A
Boysenberries
0.010000
1.000
0.060
AR
mem
Full
comment:
AR
memo
field
trials
5
13A
Raspberries
0.010000
1.000
0.050
AR
mem
Full
comment:
AR
memo
field
trials
7
13B
Blueberries
0.010000
1.000
0.010
AR
mem
Full
comment:
AR
memo
field
trials
8
O
Cranberries
0.050000
1.000
1.000
tolera
Full
comment:
tolerance
9
O
Cranberries
juice
0.050000
1.100
1.000
tolera
Full
comment:
tolerance
13
O
Grapes
0.013000
1.000
0.010
PDP
14
O
Grapes
raisins
0.013000
4.300
0.010
PDP
15
O
Grapes
juice
0.013000
1.000
0.010
PDP
52
11
Apples
0.005000
1.000
0.010
PDP
53
11
Apples
dried
0.005000
8.000
0.010
PDP
54
11
Apples
juice/
cider
0.013000
1.000
0.010
PDP
56
11
Pears
0.011000
1.000
0.010
PDP
57
11
Pears
dried
0.011000
6.250
0.010
PDP
59
12
Apricots
0.010000
1.000
0.010
other
23
Full
comment:
other
stone
fruits
60
12
Apricots
dried
0.010000
6.000
0.010
other
Full
comment:
other
stone
fruits
61
12
Cherries
0.011000
1.000
0.010
PDP
62
12
Cherries
dried
0.011000
4.000
0.010
PDP
63
12
Cherries
juice
0.011000
1.500
0.010
PDP
64
12
Nectarines
0.003000
1.000
0.010
PDP
65
12
Peaches
0.012000
1.000
0.010
PDP
66
12
Peaches
dried
0.012000
7.000
0.010
PDP
67
12
Plums
(damsons)
0.010000
1.000
0.010
other
Full
comment:
other
stone
fruits
68
12
Plums
prunes
(dried)
0.010000
5.000
0.010
other
Full
comment:
other
stone
fruits
69
12
Plums/
prune
juice
0.010000
1.400
0.010
other
Full
comment:
other
stone
fruits
176
4A
Lettuce
leafy
varieties
0.005300
1.000
1.000
PDP
178
4A
Endive
curley
and
escarole
1.000000
1.000
0.310
tolera
Full
comment:
tolerance
181
O
Artichokes
globe
0.005000
1.000
0.210
AR
mem
Full
comment:
AR
memo
field
trials
1/
2
LOD
182
4A
Lettuce
unspecified
0.005300
1.000
1.000
PDP
185
4B
Rhubarb
0.039000
1.000
1.000
AR
mem
Full
comment:
AR
memo
field
trial
average
192
4A
Lettuce
head
varieties
0.005300
1.000
1.000
PDP
195
O
Grapes
leaves
0.013000
1.000
0.010
PDP
203
1CD
Artichokes
jerusalem
0.005000
1.000
0.210
AR
mem
Full
comment:
AR
memo
field
trials
1/
2
LOD
240
6C
Peas
(garden)
dry
0.050000
1.000
0.010
tolera
Full
comment:
tolerance
315
O
Grapes
wine
and
sherry
0.013000
1.000
0.010
PDP
318
D
Milk
nonfat
solids
0.000018
1.000
1.000
AR
319
D
Milk
fat
solids
0.000018
1.000
1.000
AR
320
D
Milk
sugar
(lactose)
0.000018
1.000
1.000
AR
24
321
M
Beef
meat
byproducts
0.000120
1.000
1.000
AR
322
M
Beef
other
organ
meats
0.000120
1.000
1.000
AR
323
M
Beef
dried
0.000010
1.920
1.000
AR
324
M
Beef
fat
w/
o
bones
0.000040
1.000
1.000
AR
325
M
Beef
kidney
0.000120
1.000
1.000
AR
326
M
Beef
liver
0.000250
1.000
1.000
AR
327
M
Beef
lean
(fat/
free)
w/
o
bones
0.000010
1.000
1.000
AR
328
M
Goat
meat
byproducts
0.000120
1.000
1.000
AR
329
M
Goat
other
organ
meats
0.000120
1.000
1.000
AR
330
M
Goat
fat
w/
o
bone
0.000040
1.000
1.000
AR
331
M
Goat
kidney
0.000120
1.000
1.000
AR
332
M
Goat
liver
0.000250
1.000
1.000
AR
333
M
Goat
lean
(fat/
free)
w/
o
bone
0.000010
1.000
1.000
AR
334
M
Horsemeat
0.000010
1.000
1.000
AR
336
M
Sheep
meat
byproducts
0.000120
1.000
1.000
AR
337
M
Sheep
other
organ
meats
0.000120
1.000
1.000
AR
338
M
Sheep
fat
w/
o
bone
0.000040
1.000
1.000
AR
339
M
Sheep
kidney
0.000120
1.000
1.000
AR
340
M
Sheep
liver
0.000250
1.000
1.000
AR
341
M
Sheep
lean
(fat
free)
w/
o
bone
0.000010
1.000
1.000
AR
342
M
Pork
meat
byproducts
0.000120
1.000
1.000
AR
343
M
Pork
other
organ
meats
0.000120
1.000
1.000
AR
344
M
Pork
fat
w/
o
bone
0.000040
1.000
1.000
AR
345
M
Pork
kidney
0.000120
1.000
1.000
AR
346
M
Pork
liver
0.000250
1.000
1.000
AR
347
M
Pork
lean
(fat
free)
w/
o
bone
0.000010
1.000
1.000
AR
355
P
Turkey
byproducts
0.000140
1.000
1.000
AR
356
P
Turkey
giblets
(liver)
0.000140
1.000
1.000
AR
357
P
Turkey
fat
w/
o
bones
0.000140
1.000
1.000
AR
358
P
Turkey
lean/
fat
free
w/
o
bones
0.000140
1.000
1.000
AR
360
P
Poultry
other
lean
(fat
free)
w/
0.000140
1.000
1.000
AR
361
P
Poultry
other
giblets(
liver)
0.000140
1.000
1.000
AR
362
P
Poultry
other
fat
w/
o
bones
0.000140
1.000
1.000
AR
25
363
P
Eggs
whole
0.000140
1.000
1.000
AR
364
P
Eggs
white
only
0.000140
1.000
1.000
AR
365
P
Eggs
yolk
only
0.000140
1.000
1.000
AR
366
P
Chicken
byproducts
0.000140
1.000
1.000
AR
367
P
Chicken
giblets(
liver)
0.000140
1.000
1.000
AR
368
P
Chicken
fat
w/
o
bones
0.000140
1.000
1.000
AR
369
P
Chicken
lean/
fat
free
w/
o
bones
0.000140
1.000
1.000
AR
377
11
Apples
juice
concentrate
0.013000
3.000
0.010
PDP
380
13A
Blackberries
juice
0.010000
1.000
0.060
AR
mem
Full
comment:
AR
memo
field
trials
385
P
Chicken
giblets
(excl.
liver)
0.000140
1.000
1.000
AR
389
O
Cranberries
juice
concentrate
0.050000
3.300
1.000
tolera
Full
comment:
tolerance
392
O
Grapes
juice
concentrate
0.013000
3.000
0.010
PDP
398
D
Milk
based
water
0.000018
1.000
1.000
AR
402
12
Peaches
juice
0.012000
1.000
0.010
PDP
404
11
Pears
juice
0.011000
1.000
0.010
PDP
410
12
Apricot
juice
0.010000
1.000
0.010
other
Full
comment:
other
stone
fruits
424
M
Veal
fat
w/
o
bones
0.000040
1.000
1.000
AR
425
M
Veal
lean
(fat
free)
w/
o
bones
0.000010
1.000
1.000
AR
426
M
Veal
kidney
0.000120
1.000
1.000
AR
427
M
Veal
liver
0.000250
1.000
1.000
AR
428
M
Veal
other
organ
meats
0.000120
1.000
1.000
AR
429
M
Veal
dried
0.000010
1.920
1.000
AR
430
M
Veal
meat
byproducts
0.000120
1.000
1.000
AR
449
P
Turkey
other
organ
meats
0.000140
1.000
1.000
AR
492
O
Radicchio
2.000000
1.000
1.000
tolera
Full
comment:
tolerance
| epa | 2024-06-07T20:31:42.681845 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0159-0002/content.txt"
} |
EPA-HQ-OPP-2002-0159-0003 | Supporting & Related Material | "2002-07-12T04:00:00" | null | 1
Drinking
Water
Assessment
PronamideTRED.
wpd
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES,
AND
TOXIC
SUBSTANCES
PC
Code:
101701
DP
Barcode:
D274842
MEMORANDUM
May
16,
2001
SUBJECT:
Drinking
Water
Assessment
to
Support
TRED
for
Propyzamide
(Pronamide)
FROM:
Lucy
Shanaman,
Chemist
Environmental
Risk
Branch
IV
Environmental
Fate
and
Effects
Division
THROUGH:
Betsy
Behl,
Chief
Environmental
Risk
Branch
IV
Environmental
Fate
and
Effects
Division
R.
David
Jones,
Senior
Agronomist
Environmental
Risk
Branch
IV
Environmental
Fate
and
Effects
Division
TO:
Susan
Lewis,
Branch
Chief
Reregistration
Branch
I
Special
Review
Reregistration
Division
This
memo
presents
the
Tier
I
Drinking
Water
Assessment
for
propyzamide
calculated
using
FIRST
(surface
water)
and
SCIGROW
(groundwater)
for
use
in
the
human
health
risk
assessment.
For
surface
water,
the
acute
(peak)
value
is
390
ppb,
and
the
chronic
(average
annual)
value
is
122
ppb.
The
groundwater
screening
concentration
is
3.0
ppb.
These
concentrations
were
predicted
from
recommended
use
information
for
ornamental
herbaceous
plants,
and
represent
upper
bound
estimates
of
the
concentrations
that
might
be
found
in
surface
water
and
groundwater
due
to
the
use
of
pronamide/
propyzamine
on
registered
crops.
Should
the
results
of
this
assessment
indicate
a
need
for
further
refinement,
please
contact
us
as
soon
as
possible
so
that
we
may
schedule
a
Tier
II
assessment.
2
Drinking
Water
Assessment
PronamideTRED.
wpd
Background
Information
on
FIRST:
As
indicated
in
the
User's
Manual,
`FIRST'
is
a
first
tier
screening
model
designed
as
a
coarse
screen
to
estimate
the
pesticide
concentrations
found
in
an
`Index
Reservoir'
located
in
Shipman,
Illinois
for
use
in
environmental
risk
assessments
for
drinking
water.
As
such,
it
provides
high
end
values
on
the
concentrations
due
to
the
use
of
a
pesticide
in
drinking
water
that
might
be
found
derived
from
surface
water.
Pesticide
concentration
values
estimated
using
this
scenario
should
be
exceeded
only
rarely
in
the
source
water
at
the
intake
pipe
of
a
community
water
supply
(CWS)
systems
in
the
United
States.
This
first
level
tier
is
designed
as
a
coarse
screen
and
estimates
concentrations
from
only
a
few
basic
chemical
parameters
and
pesticide
label
application
information.
The
program
considers
reductions
in
dissolved
concentration:
(1)
due
to
the
percentage
of
the
watershed
which
is
cropped,
(2)
due
to
adsorption
of
pesticide
to
field
soil
and
to
reservoir
bottom
sediment,
(3)
due
to
incorporation
of
the
pesticide
at
the
time
of
application,
(4)
due
to
degradation
in
soil
before
washoff
to
the
reservoir,
and
(5)
due
to
degradation
of
the
pesticide
within
the
water
body.
Reservoir
water
concentrations
may
be
increased
due
to
deposition
of
spray
drift
into
the
feeding
stream
or
directly
into
the
reservoir
itself.
The
program
does
not
consider
the
impact
of
water
treatment
processes.
The
`FIRST'
program
is
designed
to
mimic
a
more
complex
simulation
such
as
using
the
linked
PRZM
and
EXAMS
models,
but
requires
less
time
and
effort
to
complete.
If
a
risk
assessment
performed
using
`FIRST'
output
does
not
exceed
the
level
of
concern,
then
one
can
be
reasonably
confident
that
the
acute
risk
will
not
be
exceeded.
However,
because
`FIRST'
can
substantially
overestimate
true
drinking
water
concentrations,
it
will
be
necessary
to
refine
the
`FIRST'
estimates
if
the
level
of
concern
is
exceeded.
Background
Information
on
SCIGROW:
SCIGROW
provides
a
groundwater
screening
exposure
value
to
be
used
in
determining
the
potential
risk
to
human
health
from
drinking
water
contaminated
with
the
pesticide.
Since
the
SCIGROW
concentrations
are
likely
to
be
approached
in
only
a
very
small
percentage
of
drinking
water
sources,
i.
e.,
highly
vulnerable
aquifers,
it
is
not
appropriate
to
use
SCIGROW
concentrations
for
national
or
regional
exposure
estimates.
SCIGROW
estimates
likely
groundwater
concentrations
if
the
pesticide
is
used
at
the
maximum
allowable
rate
in
areas
where
groundwater
is
exceptionally
vulnerable
to
contamination.
In
most
cases,
a
large
majority
of
the
use
area
will
have
groundwater
that
is
less
vulnerable
to
contamination
than
the
areas
used
to
drive
the
SCIGROW
estimate.
3
Drinking
Water
Assessment
PronamideTRED.
wpd
Modeling
Inputs
and
Results
Table
1
and
Table
2
summarize
the
general
input
values
used
in
the
model
runs
for
FIRST
and
SCIGROW,
respectively
for
pronamide
(propyzamide),
applied
four
times
by
low
pressure
ground
spray,
at
a
rate
of
two
pounds
per
acre
to
ornamental
herbaceous
plants.
FIRST
predicted
surface
water
acute
peak
concentration
is
390
ppb.
Chronic
(average
annual)
concentration
is
122
ppb.
SCIGROW
predicted
groundwater
concentration
is
3.0
ppb.
Modeling
results
for
low
pressure
ground
spray
application
to
ornamental
herbaceous
plants
appear
in
Table
3.
FIRST
and
SCIGROW
output
files
appear
at
the
end
of
this
document.
Appendix
I
summarizes
(1)
the
yearly
application
rates
for
individual
crops
as
application
rate
and
number
of
applications
per
year
(pounds/
acre)
for
(2)
specific
methods
of
application,
along
with
the
(3)
FIRST
and
(4)
SCIGROW
output
values
for
all
registered
uses.
Table
1.
Input
Parameters
for
FIRST
Chemical
propyzamide
PC
Code
101701
Water
Solubility
(25
°C)
15
mg/
L
Hydrolysis
Half
Life
(pH7)
stable
Aerobic
Soil
Metabolism
Half
Life
1176
days
(n=
1;
use
3
x
reported
half
life)
Aerobic
Aquatic
Metabolism
Half
Life
2352
days
(no
reported
value;
use
2
x
aerobic
soil
metabolism
value)
Photolysis
Half
Life
41
days
Organic
Carbon
Adsorption
Coefficient
(Koc)
504
L/
kg
(slope
of
plot,
adsorption
Kd
versus
%
organic
carbon
Application
Method
low
pressure
ground
spray
Application
Rate
2
lbs.
a.
i./
acre
Application
Frequency
4
per
year
Interval
Between
Applications
21
days
4
Drinking
Water
Assessment
PronamideTRED.
wpd
Table
2.
Input
Parameters
for
SCIGROW
Chemical
propyzamide
PC
Code
101701
Organic
Carbon
Adsorption
Coefficient
(Koc)
701
L/
kg
Aerobic
Soil
Metabolism
Half
Life
392
days
Application
Rate
2
lbs.
a.
i./
acre
Application
Frequency
4
per
year
Table
3.
Modeling
Results
Based
on
Low
Pressure
Ground
Spray
Application
of
Propyzamide
to
Ornamental
Herbaceous
Plants
Model
Concentration
FIRST
Peak
Day
(Acute)
390
ppb
FIRST
Annual
Average
(Chronic)
122
ppb
SCIGROW
Ground
Water
Value
3.
0
ppb
5
Drinking
Water
Assessment
PronamideTRED.
wpd
RUN
No.
9
FOR
Pronamide
on
ornamental
herbaceous
plants
(8
lb/
Acre,
ground
spray)
INPUT
VALUES
RATE
(#/
AC)
No.
APPS
&
SOIL
SOLUBIL
APPL
TYPE
%CROPPED
INCORP
ONE(
MULT)
INTERVAL
Koc
(PPM
)
(%
DRIFT)
AREA
(IN)
2.000(
7.854)
4
21
504.0
15.0
GROUND(
6.4)
87.0
.0
FIELD
AND
RESERVOIR
HALFLIFE
VALUES
(DAYS)
METABOLIC
DAYS
UNTIL
HYDROLYSIS
PHOTOLYSIS
METABOLIC
COMBINED
(FIELD)
RAIN/
RUNOFF
(RESERVOIR)
(RES.
EFF)
(RESER.)
(RESER.)
1176.00
2
N/
A
41.00
5084.00
******
1608.06
UNTREATED
WATER
CONC
(MICROGRAMS/
LITER
(PPB))
Ver
1.0
MAY
1,
2001
PEAK
DAY
(ACUTE)
ANNUAL
AVERAGE
(CHRONIC)
CONCENTRATION
CONCENTRATION
390.164
139.657
(Multiply
by
0.87
to
correct
error
in
program)
RUN
No.
9
FOR
Proamide
on
ornamental
herbaceous
plants
(8
lb/
Acre,
ground
spray)
INPUT
VALUES
APPL
(#/
AC)
APPL.
URATE
SOIL
SOIL
AEROBIC
RATE
NO.
(#/
AC/
YR)
KOC
METABOLISM
(DAYS)
2.000
4
8.000
701.0
392.0
GROUND
WATER
SCREENING
CONCENTRATIONS
IN
PPB
3.014783
A=
387.000
B=
706.000
C=
2.588
D=
2.849
RILP=
2.979
F=
.
424
G=
.377
URATE=
8.000
GWSC=
3.014783
6
Drinking
Water
Assessment
PronamideTRED.
wpd
APPENDIX
I
Modeling
Results
for
use
on
Registered
Crops
CROP
APPLICATION
RATE
PER
YEAR
(pounds
/
acre)
FREQUENCY
(number
of
uses
/
interval
between
use,
in
days
)
FIRST
DRINKING
WATER
VALUES
(ppb)
SCIGROW
GROUND
WATER
VALUES
(ppb)
APPLICATION
METHOD
Peak
Day
Annual
Average
C
fallow
0.
51
NA
25.96
8.29
0.192192
aircraft
C
endive
C
lettuce
2.04
NA
103.85
33.17
0.768770
aircraft
C
Christmas
tree
3.06
NA
155.78
49.76
1.153154
aircraft
C
artichoke
4.08
2
/
21
206.46
65.95
1.537539
aircraft
C
lettuce
6.12
NA
311.56
99.52
2.306309
aircraft
C
fallow
0.
51
NA
25.33
7.89
0.192192
low
pressure
ground
sprayer
C
ornamental
sod
farm
(turf)
C
peas
(filled)
1.53
NA
76.00
23.66
0.576577
low
pressure
ground
sprayer
C
alfalfa
C
blueberry
C
chicory
C
clover
C
crown
vetch
C
endive
C
grass
for
seed
C
lettuce
C
ornamental
shade
trees
C
ornamental
lawns
and
turf
C
ornamental
woody
shrubs
/
vines
C
rhubarb
C
sainfoin
C
trefoil
2.04
NA
101.33
31.55
0.768770
low
pressure
ground
sprayer
C
blackberry
C
boysenberry
C
Christmas
tree
C
raspberry
(black,
red)
3.06
NA
151.99
47.33
1.153154
low
pressure
ground
sprayer
7
Drinking
Water
Assessment
PronamideTRED.
wpd
C
lettuce
6.12
NA
303.98
94.66
2.306309
low
pressure
ground
sprayer
C
ornamental
herbaceous
plants
8
2
/
4
390.16
121.50
3.014783
low
pressure
ground
sprayer
C
sugar
beet
1.02
NA
50.66
15.77
0.384385
sprayer
C
golf
course
turf
C
recreational
areas
1.5
NA
75.50
23.20
0.565272
sprayer
C
apricot
C
apple
C
artichoke,
C
cherry
C
grapes
C
nectarine
C
peach
C
pear
C
plum
C
prune
4.08
NA
202.65
63.10
1.537539
sprayer
C
alfalfa
C
chicory
C
endive
C
lettuce
2.04
NA
101.33
31.55
0.768770
soil
incorporation
equipment
| epa | 2024-06-07T20:31:42.697596 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0159-0003/content.txt"
} |
EPA-HQ-OPP-2002-0159-0004 | Supporting & Related Material | "2002-07-12T04:00:00" | null | 1
EPA
Pesticides
in
Ground
Water
Database,
A
Compilation
Of
Monitoring
Studies:
1971
7991
National
Summary;
Office
of
Pesticide
Programs,
Environmental
Fate
and
Effects
Division;
Environmental
Fate
and
Ground
Water
Branch,
Jacoby
H.;
Pesticide
Monitoring
Program
Section,
Hoheisel
C,
Karrie
J,
Lees
S,
Davies
Hilliard
L,
Hannon
P,
Bringham
R;
Ground
Water
Technology
Section,
Behl
E,
Wells
D,
Waldman
E.
2
J.
D.
Blomquist,
J.
M.
Davis,
J.
L.
Cowles,
J.
A.
Hetrick,
R.
D.
Jones,
and
N.
B.
Birchfield.
2001.
Pesticides
in
Selected
Water
Supply
Reservoirs
and
Finished
Drinking
Water,
1
Final
Water
Assessment
PronamideTIER2.wpd
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES,
AND
TOXIC
SUBSTANCES
PC
Code:
101701
DP
Barcodes:
D281443,
D281445
MEMORANDUM
June
5,
2002
SUBJECT:
Tier
II
Drinking
Water
Assessment
to
Support
TRED
for
Pronamide
(Propyzamide)
FROM:
Lucy
Shanaman,
Chemist
Environmental
Risk
Branch
IV
Environmental
Fate
and
Effects
Division
THROUGH:
RDavid
Jones,
Senior
Scientist
Environmental
Risk
Branch
IV
Environmental
Fate
and
Effects
Division
Betsy
Behl,
Chief
Environmental
Risk
Branch
IV
Environmental
Fate
and
Effects
Division
TO:
Robert
McNally,
PM
60
Cecelia
Watson,
PM
team
reviewer
Special
Review
Branch
Special
Review
Reregistration
Division
This
memo
presents
the
Tier
II
Drinking
Water
Assessment
for
pronamide
(propyzamine)
in
surface
water,
calculated
using
PRZM/
EXAMS,
and
a
Tier
I
Drinking
Water
Assessment
in
groundwater
using
SCIGROW,
for
use
in
the
human
health
risk
assessment.
Pronamide
detections
have
been
found
in
monitoring
data
from
both
the
USGS,
NAWQA
database,
the
EPA
Pesticides
in
Ground
Water
Database
1
,
and
the
pilot
reservoir
monitoring
program
2
.
Tier
1
and
Tier
2
modeling
1999
2000:
Summary
of
Results
from
a
Pilot
Monitoring
Program.
Open
file
Report
01
456.
Baltimore,
MD.
2
Final
Water
Assessment
PronamideTIER2.wpd
results
of
the
most
current
drinking
water
exposures
for
use
of
pronamide
on
registered
crops
follows:
1.
SURFACE
WATER
(output
tables
in
Appendix
I)
EFED's
PRZM/
EXAMS
model
results
(input
parameters
in
table
1)
for
use
of
pronamide
on
registered
crops
(application
rates
of
between
1.5
4.0
lb/
acre;
Table
2)
for
drinking
water
derived
from
surface
sources:
10.3
ug/
L
(ppb)*
for
acute
exposure
from
application
to
pears
in
Oregon
(one
in
ten
year
peak
value)
4.45
ug/
L
(ppb)*
for
non
cancer
chronic
exposure
from
application
to
alfalfa
in
California
(one
in
ten
year
annual
mean
value)
4.30
ug/
L
(ppb)*
for
cancer
exposure
from
application
to
alfalfa
in
California
(overall
mean
annual
value
from
36
years)
*
Reported
values
adjusted
for
percent
crop
area
by
multiplying
by
a
factor
of
0.86,
as
dictated
by
EFED
policy.
2.
GROUND
WATER
(output
in
Appendix
II)
EFED's
SCI
GROW
model
screening
level
results
for
pronamide
groundwater
screening
concentration
for
an
application
to
all
crops
at
a
rate
of
4.0
lbs.
of
active
ingredient
per
acre:
1.1
ug/
L
(ppb)
(for
both
acute
and
chronic
exposures)
Monitoring
Data
Pronamide
detections
have
been
found
in
monitoring
data
from
the
USGS,
NAWQA
database,
EPA
Pesticides
in
Ground
Water
Database,
and
the
Pilot
Reservoir
Monitoring
Program.
The
USGS,
NAWQA
national
database
indicates
that,
out
of
almost
14
thousand
samples,
pronamide
is
detected
in
surface
water
in
<
3%
of
the
samples.
The
maximum
recorded
value
is
0.365
ppb.
Between
1984
and
1990,
a
total
of
432
wells
were
sampled
for
the
EPA
Pesticides
in
Ground
Water
Database.
No
detections
of
pronamide
were
recorded
for
tested
locations
in
California,
Mississippi,
or
Oregon.
A
total
of
12
sites
were
chosen
for
the
Pilot
Reservoir
Monitoring
Program
to
represent
locations
that
are
particularly
vulnerable
to
pesticide
contamination.
Only
one
reservoir
out
of
the
twelve,
located
in
Oklahoma,
recorded
positive
3
http://
ca.
water.
usgs.
gov/
pnsp/
use92/
pronmid.
html
3
Final
Water
Assessment
PronamideTIER2.wpd
detections
for
pronamide
of
up
to
0.044
ppb
in
83%
(34
of
41)
of
the
raw
water
samples,
and
up
to
0.012
ppb
in
42
%
(8
of
19)
of
the
finished
water
samples.
It
is
worth
noting
that
only
a
cursory
review
of
the
monitoring
data
has
been
presented
here.
It
can
not
be
determined
if
this
monitoring
data
is
representative
of
pronamide
use
nation
wide,
based
on
this
level
of
analysis.
In
none
of
these
studies,
were
sites
selected
based
on
pronamide
use
patterns.
A
more
extensive
evaluation
of
the
monitoring
data
could
reveal
what
percentage
of
the
samples
reported
were
collected
within
a
vulnerable
time
frame,
and
from
locations
where
pronamide
was
actually
being
used.
The
pesticide
use
map
below,
taken
from
the
USGS,
NAWQA
program
web
site
3
,
shows
historical
regional
scale
patterns
in
use
intensity
within
the
United
States.
The
map
is
based
on
state
level
estimates
of
pesticide
use
rates
compiled
by
the
National
Center
for
Food
and
Agricultural
Policy
(NCFAP)
for
1991,
1992,
1993
and
1995,
and
on
county
based
crop
acreage
data
obtained
from
the
1992
Census
of
Agriculture,
and
indicates
that
the
major
current
agricultural
uses
are
for
lettuce,
alfalfa,
grass
and
pears.
The
map
depicts
that
the
heaviest
historical
agricultural
uses
are
in
California,
the
Pacific
Northwest,
and
in
smaller
scattered
pockets
use
sites.
It
is
interesting
to
note
that
the
only
site
within
the
Pilot
Reservoir
Monitoring
Program
reporting
proanamide
detections
was
in
Oklahoma,
where
the
above
map
indicates
that
proanamide
does
not
have
extensive
agricultural
use.
USGS,
NAWQA
Pesticide
National
Synthesis
Project
4
soils
and
scenario
data
for
the
standard
scenarios
is
located
at:
F:\
USER\
SHARE\
Models\
Aquatic
Exposure\
PRZMEXAMS\
Scenarios\
STD_
SCEN\
Standard
Scenario
Documentation
4
Final
Water
Assessment
PronamideTIER2.wpd
Models
Used
The
Tier
2
Estimated
Environmental
Concentrations
(EEC's)
for
the
major
registered
crop
uses
were
calculated
using
two
models:
PRZM
version
3.12
(Carsel
et
al.,
1997),
dated
May
7,
1998
to
simulate
the
transport
of
the
pesticide
off
the
field,
and
EXAMS
2.97.5
(Burns,
1997),
dated
June
13,
1997,
to
simulate
the
fate
of
the
chemicals
in
the
water
body.
Both
models
were
launched
from
a
shell
(pe3)
recently
developed
within
EFED,
and
adopted
for
use
on
February
27,
2002.
SCIGROW
(version
2.1;
May
1,
2001)
provides
a
Tier
1,
groundwater
screening
exposure
value
to
be
used
in
determining
the
potential
risk
to
human
health
from
drinking
water
contaminated
with
the
pesticide.
While
use
of
this
version
is
provisional,
it
is
expected
to
produce
more
accurate
estimated
values
for
compounds
with
longer
half
lives.
In
most
cases,
a
large
majority
of
the
use
area
will
have
groundwater
that
is
less
vulnerable
to
contamination
than
the
areas
used
to
drive
the
SCIGROW
estimate.
Scenarios
Several
standard
scenarios
were
chosen
to
model
estimated
environmental
concentrations
in
surface
water
resulting
from
the
proposed
crop
uses
of
pronamide,
based
on
particularly
vulnerable
crop
sites
for
registered
uses.
Meteorological
data
files
were
adjusted
to
reflect
irrigation
amounts
required
for
wetting
in
of
pronamide,
as
per
label
recommendation,
by
including
the
required
additional
water
in
with
the
recorded
precipitation
for
each
application
date.
Four
standard,
index
reservoir
scenarios
were
chosen
as
surrogates
for
estimating
environmental
concentrations
in
sites
more
vulnerable
to
the
offsite
movement
of
pesticide
than
most
sites
planted
with
their
respective
crops.
The
standard
Oregon
apples
scenario
was
used
to
represent
application
of
pronamide
to
northwestern
pear
orchards.
The
apple
scenario
is
an
orchard
in
Marion
County,
Oregon,
MLRA
A2.
The
soil
at
the
site
is
Cornelius
silt
loam,
a
fine
silty,
mixed,
superactive,
mesic
Mollic
Fragixeralfs.
Data
for
the
Cornelius
silt
loan
was
taken
from
the
USDA
National
Cooperative
Soil
Survey,
Official
Series
Description
4
.
Weather
data
was
taken
from
wether
station
W24232,
at
Salem,
Oregon.
The
weather
data
file
is
part
of
the
PIRANHA
shell,
and
is
used
to
represent
the
weather
for
MLRA
A2.
The
standard
California
alfalfa
scenario
was
used
to
represent
application
of
pronamide
to
alfalfa
crops,
in
general.
The
alfalfa
scenario
is
a
field
in
the
central
valley
of
California,
MLRA
17.
The
soil
at
the
site
is
Sacramento
clay,
very
fine,
smectitic,
thermic
Cumulic
Vertic
Endoaquolls.
Data
for
the
Sacramento
clay
was
taken
from
the
USDA
National
Cooperative
Soil
Survey,
Official
5
soils
and
scenario
data
for
the
standard
scenarios
is
located
at:
F:\
USER\
SHARE\
Models\
Aquatic
Exposure\
PRZMEXAMS\
Scenarios\
STD_
SCEN\
Standard
Scenario
Documentation
6
soils
and
scenario
data
for
the
standard
scenarios
is
located
at:
F:\
USER\
SHARE\
Models\
Aquatic
Exposure\
PRZMEXAMS\
Scenarios\
STD_
SCEN\
Standard
Scenario
Documentation
7
soils
and
scenario
data
for
the
standard
scenarios
is
located
at:
F:\
USER\
SHARE\
Models\
Aquatic
Exposure\
PRZMEXAMS\
Scenarios\
STD_
SCEN\
Standard
Scenario
Documentation
5
Final
Water
Assessment
PronamideTIER2.wpd
Series
Description
5
.
Weather
data
was
taken
from
weather
station
W23155,
at
Bakersfield,
California.
The
weather
data
file
is
part
of
the
PIRANHA
shell,
and
is
used
to
represent
the
weather
for
MLRA
17.
The
standard
Oregon
seed
grass
scenario
was
chosen
to
represent
application
of
pronamide
to
both
field
and
seed
grass
sites.
The
seed
grass
scenario
is
a
field
in
Portland,
Oregon
in
MLRA
2.
The
soil
at
the
site
is
Dayton
silt
loam,
a
fine,
smectitic,
mesic
Vertic
Albaqualfs.
Data
for
the
Dayton
silt
loam
was
taken
from
the
USDA
National
Cooperative
Soil
Survey,
Official
Series
Description
6
.
Weather
data
was
taken
from
wether
station
W24232,
at
Salem,
Oregon.
The
weather
data
file
is
part
of
the
PIRANHA
shell,
and
is
used
to
represent
the
weather
for
MLRA
2.
The
standard
Florida
cabbage
scenario
was
chosen
to
represent
application
of
pronamide
to
east
coast
lettuce
crops.
The
Florida
cabbage
scenario
is
a
field
in
Tampa,
Florida
in
MLRA
156B.
The
soil
at
the
site
is
Riviera
sand,,
loamy,
siliceous,
active,
hyperthermic
Arenic
Glossaqualfs.
Data
for
the
Riviera
sand
was
taken
from
the
USDA
National
Cooperative
Soil
Survey,
Official
Series
Description
7
.
Weather
data
was
taken
from
weather
station
W12844,
at
West
Palm
Beach,
Florida.
The
weather
data
file
is
part
of
the
PIRANHA
shell,
and
is
used
to
represent
the
weather
for
MLRA
156B.
The
configuration
of
the
water
body
represented
by
these
standard
scenario
sites
are
a
172.8
hectare
watershed
draining
into
a
5.26
hectare
lake,
2.74
m
deep.
The
scenario
known
as
the
index
reservoir,
was
developed
to
represent
a
watershed
that
was
more
vulnerable
than
most
watersheds
to
pesticide
contamination.
It
represents
a
real
drinking
water
reservoir
in
Illinois,
Shipman
City
Lake.
The
geometry
of
the
index
reservoir
and
its
watersher
are
used
with
local
weather
and
soils
to
represent
vulnerable
watersheds
for
different
crops
in
different
regions
of
the
country.
A
detailed
description
of
the
index
reservoir
found
in
the
guidance
for
using
the
index
reservoir
(U.
S.
Environmental
Protection
Agency,
2000).
8
http://
www.
epa.
gov/
oppefed1/
models/
water/
index.
htm
6
Final
Water
Assessment
PronamideTIER2.wpd
Modeling
Inputs
and
Results
Table
1
and
Table
2
summarize
the
general
input
values
used
in
the
model
runs
for
PRZM/
EXAMS
and
SCIGROW,
respectively
for
pronamide,
applied
annually
by
ground
spray,
at
rates
between
1.5
and
4.0
pounds
per
acre
applied
to
registered
crops.
Surface
water
modeling
results
appear
in
Table
3.
PRZM/
EXAMS
and
SCIGROW
output
files
have
been
appended
to
this
document.
Table
1.
Input
Parameters
for
PRZM/
EXAMS
(pe3
shell
input)
Chemical
pronamide
Water
Solubility
(25
°C)
15
mg/
L
Hydrolysis
Half
Life
(pH7;
MRID
00107980)
stable
Aerobic
Soil
Metabolism
Half
Life
(MRID
41568901)
1176
days
Aerobic
Aquatic
Metabolism
Half
Life
2352
days
Photolysis
Half
Life
(MRID
404203
01,
40320601)
41
days
Organic
Carbon
Adsorption
Coefficient
(Koc;
MRID
40211103,
40211104)
656
L/
kg
Application
Method
ground
spray,
wetted
in
Application
Rate
1.5
to
4.0
lb/
acre
(one
annual
application)
The
PRZM/
EXAMS
input
parameters
for
metabolism
half
lives
were
selected
in
accordance
with
US
EPA
OPP
EFED
water
model
parameter
selection
guidelines,
Guidance
for
Selecting
Input
Parameters
in
Modeling
the
Environmental
Fate
and
Transport
of
Pesticides,
Version
II,
February
28,
2002
8
.
Only
one
submitted
metabolism
half
life
of
392
days
was
available
for
aerobic
soil
metabolism.
That
value
was
multiplied
by
three,
as
per
guidance
instructions.
The
resulting
value
of
1176
days
was
used
for
the
aerobic
metabolism
half
life
for
modeling.
In
the
absence
of
anaerobic
metabolism
data,
that
value
was
multiplied
by
two,
as
outlined
in
the
guidelines,
to
generate
an
anaerobic
metabolism
half
life
of
2352
days.
The
organic
carbon
adsorption
coefficient
(Koc)
value
of
656
was
calculated,
from
submitted
data,
as
the
slope
of
the
plot
of
the
adsorption
Kd
value
versus
percent
organic
carbon
of
the
specific
soils.
Submitted
data
included
several
test
soils
with
either
high
or
low
percent
organic
matter
values,
and
a
wide
variance
in
resulting
values.
While
this
is
not
the
method
recommended
in
the
input
guidance
for
calculating
the
absorption
coefficient,
this
overall
Koc
value
better
predicts
the
mobility
of
pronamide
in
the
environment.
Weather
data
was
adjusted
to
reflect
the
additional
water
needed
for
the
recommended
practice
of
"wetting
in"
the
pesticide,
by
adjusting
the
recorded
precipitation
amount
on
the
annual
application
date
to
include
the
required
additional
water.
Application
methods
and
rates
for
specific
crops
were
obtained
from
submitted
labels.
9
http://
www.
epa.
gov/
oppefed1/
models/
water/
index.
htm
7
Final
Water
Assessment
PronamideTIER2.wpd
Table
2.
Input
Parameters
for
SCIGROW
Chemical
pronamide
Organic
Carbon
Adsorption
Coefficient
(Koc)
701
L/
kg
Aerobic
Soil
Metabolism
Half
Life
392
days
Annual
Application
Rates
2
4
lbs.
a.
i./
acre
The
SCIGROW
input
parameters
were
selected
in
accordance
with
US
EPA
OPP
EFED
water
model
parameter
selection
guidelines,
Guidance
for
Selecting
Input
Parameters
in
Modeling
the
Environmental
Fate
and
Transport
of
Pesticides,
Version
II,
February
28,
2002
9
.
Application
rates
were
obtained
from
submitted
labels.
Table
3.
Modeling
Results
for
Use
on
Representative
Crops
CROP
Annual
Application
Rate
(pounds
/
acre)
Application
Method
Application
Date
PRZM/
EXAMS
Values
(ppb)*
Acute
Exposure
(one
in
10
year
peak
value)
Non
Cancer
Chronic
Exposure
(one
in
10
year
annual
mean
value)
36
Year
Average
(overall
mean
annual
value
for
36
years)
C
Lettuce
in
FL
1.5
ground
sprayer
/
wetted
in
2"
October
20
3.69
0.53
0.54
C
Seed
Grass
in
OR
1.5
ground
sprayer
/
wetted
in
1"
September
15
4.19
1.94
1.86
C
Pears
in
OR
4.0
ground
sprayer
/
wetted
in
1"
November
21
10.3
4.
05
3.
92
C
Alfalfa
in
CA
2.0
ground
sprayer
/
wetted
in
1"
January
7
7.
13
4.
45
4.
30
*
Reported
values
adjusted
for
percent
crop
area
by
multiplying
by
a
factor
of
0.86,
as
dictated
by
EFED
policy.
8
Final
Water
Assessment
PronamideTIER2.wpd
Associated
files
for
PRZM/
EXAMS
modeling
of
Proanamide
located
on
the
F
drive
at
F:\
USER\
LSHANAMA\
101701PRONAMIDE\
:
Caalfalfa.
pzr
Caalfalfa.
out
Caalfalf.
zts
Fllettuce.
pzr
Fllettuce.
out
Fllettuc.
zts
Ororchard.
pzr
Ororchard.
out
Ororchar.
zts
Orseedgrass.
pzr
Orseedgrass.
out
Orseedgr.
zts
MET156c1.
MET
MET17alf.
MET
MET2ap1.
MET
MET2gs1.
MET
setstfloEXAM.
wpd
9
Final
Water
Assessment
PronamideTIER2.wpd
APPENDIX
I
OUTPUT
TABLES
OF
DRINKING
WATER
MODELING
RESULTS
PRZM/
EXAMS
Results
for
Pronamide
Use
on
Florida
Lettuce
WATER
COLUMN
DISSOLVED
CONCENTRATION
(PPB)
YEAR
PEAK
96
HOUR
21
DAY
60
DAY
90
DAY
YEARLY
1948
4.204
4.039
3.426
2.438
1.785
0.4442
1949
4.223
4.057
3.444
2.455
1.802
0.5995
1950
4.231
4.066
3.452
2.463
1.81
0.6101
1951
4.236
4.07
3.456
2.467
1.814
0.6154
1952
4.238
4.072
3.458
2.469
1.816
0.6166
1953
4.239
4.073
3.459
2.47
1.817
0.6196
1954
4.239
4.074
3.46
2.47
1.818
0.6203
1955
4.24
4.074
3.46
2.471
1.818
0.6207
1956
4.24
4.074
3.46
2.471
1.818
0.6193
1957
4.24
4.074
3.46
2.471
1.818
0.621
1958
4.24
4.074
3.46
2.471
1.818
0.6211
1959
4.24
4.074
3.46
2.471
1.818
0.6211
1960
4.24
4.074
3.46
2.471
1.818
0.6195
1961
4.24
4.074
3.46
2.471
1.818
0.6211
1962
4.24
4.074
3.461
2.471
1.818
0.6211
1963
4.24
4.074
3.461
2.471
1.818
0.6211
1964
4.24
4.074
3.46
2.471
1.818
0.6195
1965
4.24
4.074
3.46
2.471
1.818
0.6211
1966
4.24
4.074
3.461
2.471
1.818
0.6211
1967
4.24
4.074
3.461
2.471
1.818
0.6211
1968
4.24
4.074
3.46
2.471
1.818
0.6195
1969
4.24
4.074
3.46
2.471
1.818
0.6211
1970
4.24
4.074
3.461
2.471
1.818
0.6211
1971
4.24
4.074
3.461
2.471
1.818
0.6211
1972
4.24
4.074
3.46
2.471
1.818
0.6195
1973
4.24
4.074
3.46
2.471
1.818
0.6211
1974
4.24
4.074
3.461
2.471
1.818
0.6211
1975
4.24
4.074
3.461
2.471
1.818
0.6211
1976
4.24
4.074
3.46
2.471
1.818
0.6195
1977
4.24
4.074
3.46
2.471
1.818
0.6211
1978
4.24
4.074
3.461
2.471
1.818
0.6211
1979
4.24
4.074
3.461
2.471
1.818
0.6211
1980
4.24
4.074
3.46
2.471
1.818
0.6195
1981
4.24
4.074
3.46
2.471
1.818
0.6211
1982
4.24
4.074
3.461
2.471
1.818
0.6211
1983
4.24
4.074
3.461
2.471
1.818
0.6211
Upper
Tenth
4.240*
4.074
3.461
2.471
1.818
0.6211*
Percentile
MEAN
OF
ANNUAL
VALUES
=
0.615*
*Indicates
drinking
water
assessment
endpoints
BEFORE
correction
for
percent
cropped
area,
as
pre
EFED
policy.
10
Final
Water
Assessment
PronamideTIER2.wpd
PRZM/
EXAMS
Results
for
Pronamide
Use
on
Oregon
Pears
WATER
COLUMN
DISSOLVED
CONCENTRATION
(PPB)
YEAR
PEAK
96
HOUR
21
DAY
60
DAY
90
DAY
YEARLY
1948
10.47
10.31
9.668
6.136
4.091
1.021
1949
11.4
11.23
10.54
7.012
5.887
3.905
1950
11.65
11.48
10.79
7.258
6.532
4.322
1951
11.78
11.61
10.91
7.389
6.752
4.493
1952
11.84
11.67
10.98
7.509
6.869
4.577
1953
11.89
11.72
11.02
7.573
6.932
4.638
1954
11.91
11.74
11.05
7.614
6.973
4.67
1955
11.93
11.76
11.06
7.637
6.995
4.687
1956
11.93
11.76
11.06
7.649
7.007
4.688
1957
11.94
11.77
11.07
7.653
7.011
4.701
1958
11.94
11.77
11.08
7.66
7.017
4.706
1959
11.94
11.77
11.08
7.663
7.02
4.708
1960
11.94
11.77
11.07
7.664
7.022
4.699
1961
11.94
11.77
11.08
7.661
7.0
19.707
1962
11.94
11.77
11.08
7.665
7.022
4.709
1963
11.94
11.77
11.08
7.665
7.023
4.71
1964
11.94
11.77
11.07
7.666
7.023
4.7
1965
11.94
11.77
11.08
7.662
7.03
4.708
1966
11.94
11.77
11.08
7.665
7.023
4.71
1967
11.94
11.77
11.08
7.666
7.023
4.71
1968
11.94
11.77
11.07
7.666
7.023
4.701
1969
11.94
11.77
11.08
7.662
7.02
4.708
1970
11.94
11.77
11.08
7.665
7.023
4.71
1971
11.94
11.77
11.08
7.666
7.023
4.71
1972
11.94
11.77
11.07
7.666
7.023
4.701
1973
11.94
11.77
11.08
7.662
7.02
4.708
1974
11.94
11.77
11.08
7.665
7.023
4.71
1975
11.94
11.77
11.08
7.666
7.023
4.71
1976
11.94
11.77
11.07
7.666
7.023
4.701
1977
11.94
11.77
11.08
7.662
7.02
4.708
1978
11.94
11.77
11.08
7.665
7.023
4.71
1979
11.94
11.77
11.08
7.666
7.023
4.71
1980
11.94
11.77
11.07
7.666
7.023
4.701
1981
11.94
11.77
11.08
7.662
7.02
4.708
1982
11.94
11.77
11.08
7.665
7.023
4.71
1983
11.94
11.77
11.08
7.666
7.023
4.71
Upper
Tenth
11.94*
11.77
11.08
7.666
7.023
4.71*
Percentile
MEAN
OF
ANNUAL
VALUES
=
4.558*
*Indicates
drinking
water
assessment
endpoints
BEFORE
correction
for
percent
cropped
area,
as
pre
EFED
policy.
11
Final
Water
Assessment
PronamideTIER2.wpd
PRZM/
EXAMS
Results
for
Pronamide
Use
on
Oregon
Seedgrass
WATER
COLUMN
DISSOLVED
CONCENTRATION
(PPB)
YEAR
PEAK
96
HOUR
21
DAY
60
DAY
90
DAY
YEARLY
1948
3.971
3.92
3.715
3.302
3.028
0.8523
1949
4.51
4.454
4.229
3.774
3.473
1.779
1950
4.674
4.618
4.389
3.928
3.622
1.994
1951
4.758
4.701
4.472
4.008
3.7
2.093
1952
4.804
4.747
4.517
4.052
3.743
2.145
1953
4.835
4.778
4.548
4.081
3.772
2.181
1954
4.852
4.795
4.565
4.098
3.788
2.201
1955
4.862
4.806
4.575
4.108
3.798
2.213
1956
4.865
4.808
4.578
4.111
3.801
2.216
1957
4.871
4.814
4.584
4.116
3.806
2.223
1958
4.874
4.817
4.586
4.118
3.808
2.226
1959
4.875
4.818
4.587
4.12
3.81
2.228
1960
4.873
4.816
4.585
4.118
3.808
2.224
1961
4.876
4.819
4.588
4.12
3.81
2.228
1962
4.877
4.82
4.589
4.121
3.811
2.229
1963
4.877
4.82
4.589
4.121
3.811
2.229
1964
4.874
4.817
4.586
4.119
3.809
2.225
1965
4.876
4.82
4.589
4.121
3.811
2.229
1966
4.877
4.82
4.589
4.121
3.811
2.229
1967
4.877
4.82
4.589
4.122
3.811
2.23
1968
4.874
4.817
4.586
4.119
3.809
2.225
1969
4.877
4.82
4.589
4.121
3.811
2.229
1970
4.877
4.82
4.589
4.121
3.811
2.23
1971
4.877
4.82
4.589
4.122
3.811
2.23
1972
4.874
4.817
4.586
4.119
3.809
2.225
1973
4.877
4.82
4.589
4.121
3.811
2.229
1974
4.877
4.82
4.589
4.121
3.811
2.23
1975
4.877
4.82
4.589
4.122
3.811
2.23
1976
4.874
4.817
4.586
4.119
3.809
2.225
1977
4.877
4.82
4.589
4.121
3.811
2.229
1978
4.877
4.82
4.589
4.121
3.811
2.23
1979
4.877
4.82
4.589
4.122
3.811
2.23
1980
4.874
4.817
4.586
4.119
3.809
2.225
1981
4.877
4.82
4.589
4.121
3.811
2.229
1982
4.877
4.82
4.589
4.121
3.811
2.23
1983
4.877
4.82
4.589
4.122
3.811
2.23
Upper
Tenth
4.877*
4.82
4.589
4.122
3.811
2.23*
Percentile
MEAN
OF
ANNUAL
VALUES
=
2.162*
*Indicates
drinking
water
assessment
endpoints
BEFORE
correction
for
percent
cropped
area,
as
pre
EFED
policy.
12
Final
Water
Assessment
PronamideTIER2.wpd
PRZM/
EXAMS
Results
for
Pronamide
Use
on
California
Alfalfa
WATER
COLUMN
DISSOLVED
CONCENTRATION
(PPB)
YEAR
PEAK
96
HOUR
21
DAY
60
DAY
90
DAY
YEARLY
1948
5.236
5.217
5.135
4.842
4.58
2.873
1949
6.66
6.638
6.549
6.205
5.892
3.843
1950
7.277
7.257
7.169
6.816
6.487
4.324
1951
7.632
7.611
7.527
7.171
6.835
4.616
1952
7.858
7.838
7.755
7.398
7.059
4.799
1953
7.999
7.98
7.899
7.541
7.2
4.925
1954
8.102
8.083
8.003
7.644
7.301
5.01
1955
8.168
8.149
8.07
7.71
7.366
5.066
1956
8.212
8.193
8.114
7.754
7.409
5.096
1957
8.234
8.215
8.136
7.777
7.432
5.122
1958
8.257
8.238
8.16
7.8
7.455
5.141
1959
8.271
8.252
8.174
7.814
7.468
5.152
1960
8.28
8.261
8.183
7.823
7.477
5.154
1961
8.279
8.26
8.182
7.823
7.477
5.16
1962
8.287
8.269
8.19
7.831
7.484
5.166
1963
8.291
8.272
8.194
7.834
7.488
5.169
1964
8.293
8.275
8.196
7.836
7.49
5.165
1965
8.288
8.269
8.191
7.831
7.485
5.168
1966
8.293
8.274
8.196
7.836
7.49
5.171
1967
8.295
8.276
8.198
7.838
7.492
5.172
1968
8.296
8.277
8.199
7.839
7.493
5.167
1969
8.289
8.271
8.193
7.833
7.487
5.169
1970
8.294
8.276
8.197
7.838
7.491
5.172
1971
8.296
8.277
8.199
7.839
7.492
5.173
1972
8.296
8.278
8.199
7.84
7.493
5.167
1973
8.29
8.271
8.193
7.833
7.487
5.169
1974
8.295
8.276
8.197
7.838
7.491
5.172
1975
8.296
8.277
8.199
7.839
7.493
5.173
1976
8.296
8.278
8.199
7.84
7.493
5.168
1977
8.29
8.271
8.193
7.833
7.487
5.169
1978
8.295
8.276
8.198
7.838
7.491
5.172
1979
8.296
8.277
8.199
7.839
7.493
5.173
1980
8.296
8.278
8.199
7.84
7.493
5.168
1981
8.29
8.271
8.193
7.834
7.487
5.169
1982
8.295
8.276
8.198
7.838
7.491
5.172
1983
8.296
8.277
8.199
7.839
7.493
5.173
Upper
Tenth
8.296*
8.2773
8.199
7.8393
7.493
5.173*
Percentile
MEAN
OF
ANNUAL
VALUES
=
5.001*
*Indicates
drinking
water
assessment
endpoints
BEFORE
correction
for
percent
cropped
area,
as
pre
EFED
policy.
13
Final
Water
Assessment
PronamideTIER2.wpd
APPENDIX
II
SCIGROW
Ground
Water
Results
for
Pronamide
SCIGROW
VERSION
2.1
MAY
1,
2001
RUN
No.
1
FOR
pronamide
**
INPUT
VALUES
**
APP
RATE
APPS/
TOTAL/
SOIL
AEROBIC
SOIL
METAB
(LBS/
AC)
YEAR
SEASON
KOC
HALFLIFE
(DAYS)
4.000
1
4.000
701.0
392.00
GROUND
WATER
SCREENING
CONCENTRATION
(IN
PPB)
1.0966
SCIGROW
VERSION
2.1
MAY
1,
2001
RUN
No.
2
FOR
proanamide
**
INPUT
VALUES
**
APP
RATE
APPS/
TOTAL/
SOIL
AEROBIC
SOIL
METAB
(LBS/
AC)
YEAR
SEASON
KOC
HALFLIFE
(DAYS)
2.000
1
2.000
701.0
392.00
GROUND
WATER
SCREENING
CONCENTRATION
(IN
PPB)
.5483
| epa | 2024-06-07T20:31:42.701449 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0159-0004/content.txt"
} |
EPA-HQ-OPP-2002-0159-0005 | Supporting & Related Material | "2002-07-12T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
Date:
May
23,
2002
Memorandum
SUBJECT:
Addendum
to
EPA
March
8,
2002:
Pronamide.
Tolerance
Reassesment
Eligibility
Decision
(TRED).
FROM:
Gary
Bangs,
Risk
Assessor
Reregistration
Branch
3
Health
Effects
Division
(7509C)
THROUGH:
Steve
Knizner,
Chief
Reregistration
Branch
3
Health
Effects
Division
(7509C)
TO:
Cecelia
Watson,
Chemical
Review
Manager
Special
Review
and
Reregistration
Division
(7508C)
PC
Code:
Pronamide
101701.
DPBarcode:
D282842
PURPOSE:
Pronamide
Revised
Aggregate
Risk
Estimates
After
Application
of
Labeling
Changes
to
Eliminate
Use
on
Residential
Turf
2
Pronamide
Revised
Aggregate
Risk
Estimates
After
Application
of
Labeling
Changes
to
Eliminate
Use
on
Residential
Turf
Cancellation
of
the
single
label
allowing
application
of
pronamide
to
home
lawns
and
recreational
turf
will
make
children's
oral
non
dietary
exposures
unlikely.
However,
since
the
registrant
wants
to
retain
use
on
golf
courses
and
athletic
fields,
the
potential
for
low
and
highcontact
exposures
for
adults
still
exists.
Based
on
the
use
pattern
of
pronamide
(the
elimination
of
selected
grasses
from
golf
course
and
professional
playing
field
turf)
it
is
anticipated
that
children
would
rarely
be
exposed
to
pronamide
residues.
Labels
should
strongly
encourage
watering
in
to
reduce
residues,
and
management
practices
to
restrict
entry
until
the
pronamide
product
is
watered
into
the
turf.
Given
these
proposed
restrictions
on
the
use
of
pronamide
on
turf,
the
high
contact
dermal
exposure
scenario
is
not
considered
likely
and
would
result
in
an
overestimate
of
player
exposure.
Short
term
Aggregate
Risk
Estimates
The
short
term
food,
water,
and
low
contact
dermal
(golfing)
pronamide
exposures
were
aggregated
in
the
Risk
Assessment,
and
the
estimated
environmental
concentrations
(EECs)
modeled
using
Sci
Grow
and
PRZM
EXAMS
did
not
exceed
the
drinking
water
level
of
concern
(DWLOC)
.
Therefore,
risk
estimates
for
all
pathways
of
exposure
are
not
of
concern
for
pronamide
in
the
short
term
when
pronamide
use
is
restricted
per
the
label
changes
cited
above.
Chronic
Aggregate
Risk
Estimates
The
chronic
risk
estimates
would
remain
the
same
for
all
populations
as
stated
in
the
Risk
Assessment,
as
there
are
no
anticipated
long
term
non
dietary
exposure
scenarios
for
pronamide.
All
aggregate
food
and
water
estimates
do
not
exceed
the
level
of
concern.
Cancer
Risk
Estimates
Aggregate
cancer
risk
estimates
will
be
reduced
by
restricting
non
agricultural
uses
to
turf
for
sod
and
seed,
ornamental
landscaping,
industrial
sites,
professional
athletic
fields,
and
golf
courses.
Golfing
is
believed
to
be
a
representative
scenario
for
likely
exposures
to
the
public.
The
cancer
risk
estimate
for
golfing
a
single
day
per
year
is
about
the
same
as
the
dietary
cancer
risk
estimate,
or
1
x
10
7
.
When
both
dietary
and
non
dietary
risk
are
added,
the
cancer
risk
estimate
is
2.2
x
10
7
.
The
DWLOC
for
the
aggregated
dietary
and
golfing
cancer
risks
is
1.06
ppb.
Without
golf
course
exposure
(i.
e.,
no
recreational
turf
uses
at
all),
the
cancer
DWLOC
of
1.2
ppb
is
based
on
dietary
exposure
alone.
The
Tier
2
PRZM
EXAMS
37
year
mean
EECs
are
0.535
4.35
ppb.
This
modeling
was
based
on
the
maximum
label
rates
for
pronamide,
whereas
typical
rates
for
many
crops
are
25%
50%
less.
No
targeted
water
monitoring
data
were
available,
but
USGS
water
monitoring
data
showed
maximum
pronamide
levels
of
0.82
ppb
in
ground
water
and
0.365
ppb
in
surface
water.
Further
refinement
of
drinking
water
modeling
estimates
and/
or
targeted
monitoring
of
water
sources
in
high
pronamide
use
areas
would
provide
more
confidence
in
the
risk
assessment.
3
Risk
Characterization
The
cancer
risk
estimate
for
playing
on
treated
turf
used
the
turf
residues
averaged
over
14
days,
which
is
how
long
pronamide
takes
to
dissipate
to
negligible
levels.
A
single
day's
exposure
was
used,
based
on
the
national
average
rate
of
golfing
of
18
times
per
year,
or
about
every
2
weeks.
The
residential/
recreational
exposure
estimates
are
based
on
a
default
dermal
absorption
value
of
100%,
therefore,
a
dermal
absorption
study
would
help
to
reduce
these
risk
estimates.
Additional
label
language
encouraging
prompt
watering
in
of
the
product
would
help
to
reduce
available
residues
(as
shown
in
the
submitted
turf
residue
study)
and
thereby
also
reduce
risks.
| epa | 2024-06-07T20:31:42.706238 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0159-0005/content.txt"
} |
EPA-HQ-OPP-2002-0159-0006 | Supporting & Related Material | "2002-07-12T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
Date:
March
7,
2002
Memorandum
SUBJECT:
Pronamide:
Residential
Risk
Assessment
and
Recommendations
for
the
Tolerance
Reassessment
Eligibility
Decision
(TRED)
Document.
FROM:
Barry
O'Keefe,
Biologist
Reregistration
Branch
3
Health
Effects
Division
(7509C)
THROUGH:
Catherine
Eiden,
Senior
Scientist
Reregistration
Branch
3
Health
Effects
Division
(7509C)
TO:
Gary
Bangs,
Risk
Assessor
Reregistration
Branch
3
Health
Effects
Division
(7509C)
PC
Code:
101701
DP
Barcode:
D275538
Pronamide
study
MRID:
44952501
This
is
a
preliminary
exposure
and
risk
assessment.
The
assessment
is
limited
to
registered
residential
uses
of
pronamide.
Pronamide
is
a
restricted
use
pesticide,
and
therefore
requires
professional
applicators.
HED
has
determined
that
there
is
a
potential
for
exposure
in
occupational
settings
from
handling
pronamide
products
during
the
application
process
(i.
e.,
mixer/
loader,
applicator
and
mixer/
loader/
applicator)
and
from
entering
previously
treated
areas.
As
a
result,
risk
assessments
would
normally
have
been
completed
for
occupational
handler
and
postapplication
scenarios.
The
occupational
handler
and
postapplication
risk
assessment
was
previously
performed
as
part
of
the
pronamide
reregistration
eligibility
decision
(RED)
document
completed
in
May,
1994.
However,
for
pronamide
the
occupational
handler
and
postapplication
scenarios
will
not
be
assessed
now,
since
this
assessment
is
only
for
a
tolerance
reassessment
eligibility
decision
(TRED)
document.
Additionally,
the
determination
of
the
status
of
the
Agency's
occupational
exposure
data
base
for
regulatory
purposes
was
not
performed.
When
an
occupational
risk
assessment
is
performed
data
gaps
may
be
identified,
and
additional
data
and/
or
studies
may
be
required.
No
residential
exposure
data
and/
or
specific
studies
are
required
at
this
time.
2
TABLE
OF
CONTENTS
EXECUTIVE
SUMMARY......................................................
3
1.
BACKGROUND
.......................................................
10
1.
1
Purpose.........................................................
10
1.2
Criteria
for
Conducting
Exposure
Assessments
.........................
10
1.3
Summary
of
Toxicity
Concerns
Relating
to
Residential
Exposures
..........
10
1.
4
Incident
Reports..................................................
12
1.
5
Summary
of
Use
Patterns
and
Formulations
............................
13
2.0
RESIDENTIAL
AND
OTHER
NON
OCCUPATIONAL
EXPOSURES
AND
RISKS
.....................................................................
17
2.1
Methods
of
Estimating
Non
Cancer
Risks
And
Calculating
Exposures
.............
17
2.2
Residential
Handler
Exposures
and
Risks
....................................
19
2.2.1
Residential
Handler
Exposure
Scenarios,
Data,
and
Assumptions
...........
19
2.3
Non
Occupational
Postapplication
Exposure
and
Risk
Estimates
.................
19
2.3.1
Postapplication
Exposure
Scenarios,
Data,
and
Assumptions
...............
19
2.3.2
Postapplication
Exposure
and
Non
Cancer
Risk
Estimates
................
25
2.3.3
Postapplication
Cancer
Risk
Estimates
................................
26
2.3.4
Summary
of
Postapplication
Risks,
Data
Gaps,
and
Confidence
in
Exposure
and
Risk
Estimates
...................................................
27
2.4
RESIDENTIAL
AND
NON
OCCUPATIONAL
RISK
CHARACTERIZATION
....
28
2.4.1
Residential
Handler
Risk
Characterization
.............................
28
2.4.2
Non
Occupational
Postapplication
Risk
Characterization
.................
28
References
..................................................................
29
Appendix
Pronamide
Exposure
and
Risk
Estimates
Tables
4
through
7
....................
30
Table
4.
Summary
of
Postapplication
Turf
Transferable
Residue
Study
..................
31
Table
5.
Pronamide
Residential
Postapplication
Activities
on
Treated
Turf:
Dermal
Exposure
and
Non
Cancer
Risk
Estimates
...........................................
32
Table
6.
Pronamide
Postapplication
Dermal
Cancer
Risk
Estimates
for
Activities
on
Treated
Turf
.................................................................
33
Table
7.
Residential
Oral
Nondietary
Short
Term
Postapplication
Risks
to
Children
from
"Hand
to
Mouth"
and
Ingestion
Exposure
When
Reentering
Treated
Lawns
........
34
3
EXECUTIVE
SUMMARY
Background:
Use
Pronamide
is
a
restricted
use,
selective
pre
and
postemergent
herbicide
used
to
control
grasses
and
broadleaf
weeds.
It
is
applied
as
a
liquid
spray,
which
is
packaged
in
water
soluble
pouches
and
then
mixed
in
water
before
application.
It
is
a
soil
active
systemic
herbicide
with
uptake
by
susceptible
weeds
occurring
through
the
roots.
Therefore,
to
be
effective,
pronamide
is
applied
to
the
soil
and
transported
by
water
into
the
root
zone
where
it
is
taken
up
by
plants.
Pronamide
is
applied
in
the
late
Fall
and/
or
late
Winter,
only
by
certified
pesticide
applicators
and
professional
lawn
care
operators
(LCOs).
Pronamide
is
registered
for
use
in
agricultural,
ornamental,
and
residential
settings.
There
are
two
manufacturers
of
pronamide
end
use
products
with
only
two
active
section
3
registrations.
There
are
also
nine
active
24C
registrations.
Major
food/
feed
crops
include:
stone
fruits
(apricot,
cherry,
nectarine,
peach,
plum,
prune),
pome
fruits
(apple,
pear),
grapes,
artichokes,
berries
(blackberry,
blueberry,
boysenberry,
red
raspberry,
black
raspberry),
leafy
greens
(lettuce,
endive,
radicchio),
winter
peas,
chicory,
rhubarb,
sugarbeets,
and
forages
(alfalfa,
clover,
birdsfoot
trefoil,
crown
vetch,
sainfoin).
Non
agricultural
uses
include
woody
ornamentals,
ornamental
warm
season
grasses
grown
for
turf
(i.
e.
bermudagrass,
Zoysiagrass,
St.
Augustine,
and
Centipedegrass)
or
seed
(bermudagrass),
residential/
recreational
turf
(bermudagrass
lawns,
playing
fields,
and
golf
courses),
Christmas
trees,
grasses
grown
for
seed,
rangeland,
and
fallow
land.
There
is
a
potential
for
exposure
from
commercial
applications
to
agricultural
and
residential/
recreational
areas.
Therefore,
normally
both
occupational
and
residential
exposure
assessments
would
be
conducted.
However,
since
this
is
a
Tolerance
Reassessment
Eligibility
Decision
(TRED)
document,
only
a
residential
postapplication
exposure
assessment
was
conducted;
i.
e.
for
residential/
recreational
turf
uses.
Hazard
Profile
As
reported
by
the
Hazard
Identification
Assessment
Review
Committee
(HIARC)
2
,
for
shortterm
(1
30
days)
incidental
oral
exposures
an
adjusted
dose
of
8.46
mg/
kg/
day
was
established
for
use
in
this
risk
assessment.
This
dose
is
derived
from
the
no
observed
adverse
effect
level
(NOAEL)
from
a
chronic
toxicity/
carcinogenicity
study
in
rats,
where
the
effects
are
increased
liver
weight
and
non
neoplastic
histologic
changes
in
liver,
thyroid,
and
ovaries
observed
at
the
lowest
observed
adverse
effect
level
(LOAEL)
of
42.6
mg/
kg/
day.
The
dose
selection
is
based
on
a
maternal
toxicity
NOAEL
of
5
mg/
kg/
day
and
clinical
signs
of
toxicity
(soiled
anal
area
and
anorexia)
and
liver
effects
(punctate
vacuolation
of
hepatocytes)
observed
at
the
LOAEL
of
20
mg/
kg/
day
in
the
developmental
toxicity
study
conducted
in
rabbits.
Although
this
study
is
of
the
appropriate
route
(oral)
and
duration
(13
days),
the
NOAEL
(5
mg/
kg/
day)
in
this
study
is
lower
than
the
NOAEL
(8.46
mg/
kg/
day)
established
in
the
chronic
toxicity/
carcinogenicity
study
in
the
rat.
The
apparent
disparity
between
these
NOAELs
is
driven
by
the
doses
of
pronamide
selected
for
testing
in
these
studies.
The
HIARC
concluded
that
using
a
more
realistic
NOAEL
of
8.46
mg/
kg/
day,
rather
than
5
mg/
kg/
day,
would
provide
a
sufficiently
4
protective
dose
for
risk
assessment.
The
NOAEL
of
3
mg/
kg/
day
established
in
the
special
thyroid
study
conducted
in
male
rats
was
also
considered.
However
this
dose
was
not
selected
because
the
wide
gap
between
the
NOAEL
(3
mg/
kg/
day)
and
the
LOAEL
(67
mg/
kg/
day)
in
this
study
resulted
in
the
3
mg/
kg/
day
dose
(NOAEL)
being
artificially
low.
In
addition,
the
LOAEL
of
67
mg/
kg/
day
is
comparable
to
the
LOAEL
(56
mg/
kg/
day)
established
in
the
chronic
toxicity/
carcinogenicity
study
conducted
in
rats.
For
short
term
(1
30
days)
dermal
exposures
the
same
oral
dose
and
endpoint
was
selected
for
risk
assessment,
i.
e.
8.46
mg/
kg/
day.
A
dermal
absorption
factor
is
needed,
since
the
endpoint
is
based
on
a
study
using
oral
dosing.
A
default
dermal
absorption
factor
of
100%
relative
to
oral
absorption
was
chosen
by
the
HIARC,
since
the
dermal
absorption
study
sent
to
the
Agency
was
classified
as
unacceptable
(i.
e.
unable
to
verify
amount
applied
and
poor
recovery
data)
and
no
dermal
toxicity
studies
were
submitted.
In
accordance
with
the
Agency's
Proposed
Guidelines
for
Carcinogen
Risk
Assessment
(September
30,
1992),
the
HED
Carcinogenicity
Peer
Review
Committee
(CPRC)
classified
pronamide
as
a
Group
B2
chemical)
probable
human
carcinogen
with
inadequate
evidence
in
humans).
This
decision
was
based
on
the
finding
of
two
types
of
tumors
in
the
rat
(benign
testicular
interstitial
cell
tumors
and
uncommon
thyroid
follicular
cell
adenomas),
and
one
type
of
tumor
in
the
mouse
(hepatocellular
adenomas
and
carcinomas).
A
linear,
low
dose
approach
(Q1
*
)
is
used
for
human
risk
characterization.
The
most
potent
unit
risk
Q1
*
,
based
on
male
mouse
liver
adenoma
and/
or
carcinoma
combined
tumor
rates,
is
2.59
x
10
2
(mg/
kg/
day)
1
in
human
equivalents
[converted
from
animal
to
humans
by
use
of
the
(mg/
kg
body
weight)
3/
4
interspecies
scaling
factor].
Therefore,
the
Hazard
Identification
Assessment
Review
Committee
(HIARC)
recommended
that
a
cancer
risk
assessment
be
conducted
for
pronamide
(November
6,
2001).
In
a
memo
dated
December
19,
2001,
the
FQPA
Safety
Factor
Committee
recommended
that
the
FQPA
safety
factor
be
reduced
to
3x.
The
FQPA
Committee
determined
that
the
safety
factor
is
necessary
when
assessing
the
risk
posed
by
pronamide
because
of
evidence
of
endocrine
effects.
The
FQPA
safety
factor
is
required
for
all
population
subgroups
when
assessing
residential
exposures
of
all
durations.
Residential
Exposure
Estimates
Background
When
the
pronamide
RED
document
was
completed
in
May,
1994,
the
Agency
did
not
have
the
data
to
make
a
reregistration
decision
on
pronamide
for
use
on
residential
lawns.
An
estimate
of
risk
was
not
feasible
because
of
numerous
uncertainties
in
potential
exposure
levels,
especially
for
children.
In
the
1994
RED
document,
regulatory
decisions
concerning
postapplication
reentry
to
residential
lawns
were
postponed
until
after
the
submittal
and
review
of
studies
5
required
to
support
the
residential
lawn
use;
i.
e.
foliar
dislodgeable
dissipation
(old
guideline
132
1(
a)
or
new
guideline
875.2100)
and
dermal
passive
dosimetry
(old
guideline
133
3
or
new
guideline
875.2400).
In
the
interim
since
1994,
a
turf
transferrable
residue
(TTR)
study
was
submitted,
reviewed,
and
found
acceptable
and
useful
for
some
aspects
of
risk
assessment.
The
study
provided
the
required
residue
dissipation
data.
The
methodology
used
to
determine
turf
transferability
(i.
e.
the
modified
California
roller
method)
does
not
match
the
Agency's
current
methodology
(i.
e.
Jazzercise
and
the
California
roller
method)
used
to
determine
the
dermal
transfer
coefficient
on
turf.
Note,
that
the
Outdoor
Residential
Exposure
Task
Force
(ORETF)
is
currently
funding
a
study
which
is
intended
to
provide
concurrent
TTR
and
transfer
coefficient
data
for
a
surrogate
chemical.
The
requirement
for
a
dermal
passive
dosimetry
study
remains
outstanding.
However,
the
Agency
can
perform
an
adequate
risk
assessment
to
estimate
risk
on
residential
lawns
by
using
dissipation
data
from
the
TTR
study
in
conjunction
with
the
transferability
assumptions
and
equations
found
in
the
Agency's
residential
SOPs.
Short
Term
Exposure
Scenarios
A
review
of
incident
data
sources
found
that
relatively
few
incidents
of
pronamide
poisonings
were
reported.
1
There
are
only
two
Poison
Center
reports,
no
incident
reports
in
OPPs
Incident
Data
System
and
only
two
reports
from
the
California
Pesticide
Illness
Surveillance
Program.
In
sum,
recommendations
based
on
the
few
incidents
reported
are
unlikely.
All
pronamide
end
use
products
are
labeled
as
restricted
use
pesticides.
Therefore,
residents
are
restricted
from
handling
or
applying
pronamide
products.
Consequently,
only
residential/
recreational
postapplication
exposures
to
the
general
population
are
anticipated
and
are
evaluated
in
this
assessment.
Adults
and
children
are
potentially
exposed
to
pronamide
residues
after
application
of
pronamide
products
by
professional
lawn
care
operators
(LCOs)
in
residential/
recreational
settings.
Applications
are
made
to
lawns,
playing
fields,
and
golf
courses.
After
application
to
turf,
short
term
dermal
exposures
are
anticipated
for
adults
and
children.
Incidental
oral
exposure
is
also
expected
to
occur
for
small
children
and
is
combined
with
their
dermal
exposures,
where
applicable
(i.
e.,
playing
on
turf).
Residential
exposures
have
been
estimated
based
on
label
application
frequency
and
timing,
and
the
persistence
of
pronamide.
Most
assumptions
for
risk
estimation
were
based
on
the
Residential
SOPs
(see
section
2.0).
Residents
are
assumed
to
play
or
work
on
treated
lawns,
or
play
golf
within
the
first
24
hours
of
spraying.
Restrictions
on
early
re
entry
are
impractical
and
unenforceable
for
residents.
Therefore,
short
term
risks
from
residential
postapplication
dermal
and
incidental
oral
exposures
are
anticipated
and
were
estimated
for
pronamide.
No
intermediate
or
long
term
exposure
scenarios
(i.
e.
>
30
days)
are
anticipated,
since
turf
residues
dissipate
rapidly
to
below
the
limit
of
quantification
by
day
14
following
application
(pronamide
TTR
study).
The
short,
intermediate,
and
long
term
endpoints
are
the
same.
Postapplication
exposures
via
the
inhalation
route
are
not
anticipated,
since
pronamide
is
applied
as
a
liquid,
and
is
a
mobile
systemic
herbicide,
which
when
watered
in
(as
directed
on
the
label)
quickly
moves
into
soil,
where
it
is
rapidly
absorbed
into
vegetation.
Additionally,
the
uses
and
primary
exposures
are
6
outdoors,
allowing
for
significant
dilution.
The
scenarios
assessed
for
the
purpose
of
determining
risk
estimates
included
adults
and
children
(toddlers)
performing
high
contact
play
or
work
activities
on
treated
lawns,
and
adults
mowing
lawns
or
golfing.
Small
children
(toddlers)
were
also
assessed
for
incidental
oral
exposure
from
ingestion
of
soil,
object
to
mouth
activity
(turfgrass
mouthing),
and
hand
to
mouth
activity
while
playing
on
treated
lawns.
Some
of
these
exposures
were
combined,
where
it
was
deemed
reasonably
likely
that
activities
would
co
occur.
Residential
risk
estimates
utilized
data
from
a
submitted
turf
transferable
residue
(TTR)
study,
as
well
as
the
EPA's
original
and
revised
Draft
SOPs
for
Residential
Exposure
Assessment.
3,
5
For
pronamide
short
term
non
occupational
risks,
HED
has
established
a
level
of
concern
for
MOEs
<
300.
Wherever
available,
reported
usage
data
are
used
in
this
process
to
define
values
such
as
application
rates
and
application
frequency.
Only
one
end
use
product
label
can
be
used
in
a
residential
setting.
This
residential
label
(EPA
Reg.
No.
8660
85)
indicates
a
maximum
application
rate
of
1.5
lb
ai/
acre
for
pre
emergence
applications
by
lawn
care
operators
(LCOs)
to
lawns,
playing
fields,
and
golf
courses
as
a
single
application.
The
maximum
application
rate
for
post
emergence
applications
is
1.0
lb
ai/
acre.
The
label
indicates
that
typical
application
rates
for
pre
and
post
emergence
applications
are
at
0.5
to
1.0
lb
ai/
acre,
with
the
maximum
rate
being
used
in
areas
of
heavy
growth
weeds.
This
residential
label
does
not
specify
or
restrict
the
number
of
applications
allowed
per
year
to
turf.
However,
the
agricultural
label
(EPA
Reg.
No.
707
159)
allows
only
one
application
per
year
to
grasses
grown
for
turf
or
seed.
For
both
labels,
applications
to
turf
are
only
made
in
the
late
Fall
or
late
Winter.
For
residential
turf,
it
is
reasonable
to
assume
that
typically
only
one
application
is
made,
and
potentially
only
two
applications
would
be
made
in
any
year.
If
two
applications
were
made,
one
would
probably
be
made
in
late
Fall,
followed
by
another
application
in
late
Winter.
Therefore,
HED
assumed
one
application
per
year
to
estimate
short
term
exposures.
Results
from
environmental
fate
studies
indicate
that
pronamide
is
very
persistent
in
soil
and
water
with
half
lifes
of
many
months.
Additionally,
rotational
crop
studies
show
accumulation
in
several
crop
types
at
one,
six
and
twelve
months
after
application.
Results
from
a
recent
turf
transferable
residue
study
on
turf
using
pronamide
(i.
e.
MRID
44952501)
indicate
that
the
halflife
of
turf
transferrable
(TTR)
residues
was
slightly
less
than
two
days.
The
residential
label
(EPA
Reg.
No.
8660
85)
instructs
applicators
to
lightly
irrigate
within
a
day
of
application
if
no
rain
occurs.
Such
irrigation
occurred
at
24
hours
after
application
in
the
TTR
study.
Since
the
compound
is
soluble
in
water,
and
therefore
mobile,
it
is
likely
the
irrigation
dissolves
the
compound
and
transports
it
from
the
turf
into
the
soil.
Study
data
showed
that
residues
dissipate
to
below
the
level
of
quantification
by
day
14
following
application.
Therefore,
only
short
term
(i.
e.,
one
day
to
one
month)
exposures
would
be
anticipated,
since
most
of
the
pesticide
should
move
into
the
soil,
and
any
remaining
foliar
residues
should
dissipate
within
a
month.
While
residues
in
soil
could
persist
for
greater
than
30
days,
it
is
unlikely
that
children
will
play
on
or
contact
soil
for
greater
than
30
consecutive
days
during
the
late
Fall
or
late
Winter
months.
The
HED
always
completes
short
term
risk
assessments
using
maximum
application
rates
for
7
each
scenario
because
what
is
possible
under
the
label
(the
legal
means
of
controlling
pesticide
use)
must
be
evaluated
for
complete
stewardship
in
order
to
ensure
the
HED
has
no
risk
concern
for
the
specific
use.
Cancer
Exposure
Scenario
The
low
dose
extrapolation
model
used
to
estimate
the
Q1
*
assumes
that
any
exposure
at
any
time
may
increase
the
risk
of
cancer.
Therefore,
HED
conducted
an
exposure
assessment
for
cancer
based
on
residential
exposures
to
pronamide.
The
same
residential
exposure
scenarios
assumed
under
the
short
term
exposure
assessment
were
used
as
the
basis
of
the
exposure
scenario
for
cancer.
Based
on
the
pesticide
label,
a
typical
residential/
recreational
lawn
application
rate
of
1.0
lb/
acre,
with
an
application
frequency
of
once
per
year,
was
assumed
for
the
residential
cancer
risk
assessment.
Pronamide
is
applied
in
the
dormant
season,
which
reduces
the
number
of
contact
days
expected.
A
single
exposure
is
deemed
more
likely,
but
up
to
14
days
exposure
could
occur
based
on
the
residue
dissipation
pattern.
The
14
day
average
turf
residues
from
the
TTR
study
(MRID
44952501)
were
used
(i.
e.
0.07913
F
g/
cm
2
,
when
adjusted
to
a
typical
application
rate
of
1.0
lb
ai/
acre);
since
residues
in
the
TTR
study
dissipated
to
the
level
of
quantitation
by
14
days
after
application.
The
average
residue,
and
an
exposure
frequency
of
one
day
per
year,
or
50
days
in
a
lifetime,
was
assumed
for
high
contact
activities
(e.
g.
playing
and
working
on
lawns
and
turf)
and
low
contact
activities
(e.
g.
mowing
or
golfing).
Residential
Postapplication
Short
Term
Risk
Estimates
The
level
of
concern
(LOC)
for
residential
risks
for
short
term
dermal
and
incidental
oral
exposures
is
set
by
the
HED
at
a
margin
of
exposure
(MOE)
<
300.
Turf
transferrable
residue
(TTR)
data
from
the
pronamide
TTR
study
provided
by
the
registrant
were
used
quantitatively
in
this
risk
assessment.
Risk
estimates
based
on
residue
data
from
the
TTR
study
for
short
term
dermal
contact
with
treated
turf
during
high
contact
lawn
activities
on
day
zero
following
application
(DAT
0)
exceed
HED's
level
of
concern,
i.
e.
result
in
MOEs
<
300
for
adults
(MOE
=
71)
and
children
(MOE
=
42).
However,
using
DAT
2
residue
data
from
the
TTR
study
yielded
MOEs
that
do
not
exceed
the
level
of
concern
(MOEs
$
300)
for
adults
(MOE
=
890)
and
children
(MOE
=
530)
during
high
contact
lawn
activities.
Note
that
the
test
plots
were
irrigated
immediately
after
the
DAT
1
samples
were
taken,
i.
e.
24
hours
after
application
of
pronamide,
as
specified
on
the
label.
The
data
show
that
watering
in
the
pronamide
product
clearly
alleviates
these
risk
concerns.
Risk
estimates
for
short
term
dermal
contact
with
residues
on
treated
turf
during
the
low
contact
activities
of
grass
mowing
or
golfing
on
the
day
of
treatment
(DAT
0)
do
not
exceed
the
level
of
concern
(MOEs
$
300)
for
adults
(MOEs
2100
and
1000,
respectively)
(See
Table
5.)
HED
also
assessed
short
term
risks
to
small
children
from
incidental
oral
ingestion
of
pronamide
residues
following
application
to
residential
lawns
(see
Table
7).
The
risk
calculations
for
small
8
children's
non
dietary
ingestion
of
pronamide
on
treated
turf
indicate
that
risks
do
not
exceed
the
level
of
concern
(i.
e.
MOEs
$
300)
for
incidental
hand
to
mouth
activity
(MOE
=
380),
incidental
ingestion
of
soil
(MOE
=
113,000),
and
incidental
object
to
mouth
activity
(MOE
=
1500).
The
small
children's
combined
oral
hand
to
mouth
scenarios
(MOE
=
300)
also
do
not
exceed
the
level
of
concern.
When
risks
from
dermal
exposures
from
pronamide
to
small
children
are
combined
with
risks
from
incidental
oral
exposures,
the
combined
short
term
risk
estimates
exceed
the
level
of
concern
(MOEs
<
300),
with
an
MOE
at
37.
However,
the
likelihood
of
all
incidental
oral
exposures
co
occurring
with
dermal
exposures
is
low.
Residential
Postapplication
Cancer
Risk
Estimates
The
HED
endeavors
to
reduce
estimated
cancer
risks
for
the
general
population
to
less
than
one
in
one
million
(10
6
).
Estimated
adult
cancer
risks
were
calculated
using
the
same
residential
exposure
scenarios
as
described
above;
i.
e.
performing
high
contact
play
or
work
activities
on
treated
lawns,
mowing
lawns
or
golfing.
An
adult
mowing
a
treated
lawn
has
a
cancer
risk
of
5.73
x
10
8
.
The
adult
golfer
cancer
risk
is
estimated
at
1.15
x
10
7
.
An
adult
performing
dermal
high
contact
activities
on
turf
has
a
cancer
risk
of
8.36
x
10
7
.
In
order
to
exceed
the
cancer
risk
(1.0
x
10
6
),
exposure
frequencies
of
17.5,
8.7
and
1.2
days
per
year
would
be
needed
for
the
activities
of
mowing,
golfing
and
high
contact
work,
respectively.
Summary
of
Risk
Concerns,
Exposure
Assumptions,
and
Confidence
in
Estimates
The
exposure
estimates
generated
for
the
residential/
recreational
turf
uses
used
the
HED
SOPs
that
are
based
on
some
upper
percentile
assumptions
(i.
e.,
duration
of
exposure
and
maximum
application
rate
for
short
term
assessments)
and
are
considered
to
be
representative
of
high
end
exposures.
The
uncertainties
associated
with
this
assessment
stem
from
the
use
of
assumptions
regarding
the
transfer
of
pronamide
residues.
The
exposure
estimates
are
believed
to
be
reasonably
high
end
estimates,
since
the
maximum
application
rate
is
used,
a
100%
dermal
absorption
factor
is
assumed,
and
exposures
are
assumed
to
occur
on
the
day
of
treatment.
The
translation
of
a
dose
based
on
a
chronic
effect
for
the
purpose
of
short
term
risk
estimation
also
contributes
to
a
high
end
exposure
estimate.
However,
dermal
exposure
estimates
are
not
considered
overly
conservative,
since
turf
transferrable
residue
(TTR)
data
from
a
pronamide
TTR
field
study
was
used;
specifically
0.289
µg/
cm
2
,
which
is
the
average
residue
observed
on
day
zero
after
application,
and
represents
1.65%
of
the
pronamide
applied
(i.
e.
the
transfer
efficiency).
The
study
was
acceptable
and
met
the
OPPTS
guidelines,
so
the
level
of
confidence
is
fairly
high.
There
is
less
confidence
in
the
oral
risk
estimates,
which
are
solely
based
on
the
HED
SOPs.
HED
assumes
that
the
general
public's
exposure
may
not
be
mitigated
by
use
of
personal
protective
gear.
Therefore,
only
administrative
controls
(e.
g.,
formulation
changes
or
use
rate
reductions)
are
feasible
methods
of
risk
reduction.
Mitigating
circumstances
for
residential
exposure
to
pronamide
residues
may
include
the
watering
in
of
the
product
to
turf
immediately
after
application,
instead
of
within
24
hours
after
application,
as
the
label
currently
recommends.
Pronamide
product
was
watered
in
for
the
TTR
study
(MRID
44952501).
This
instruction,
9
however,
does
not
prevent
contact
with
treated
turf
prior
to
watering
in.
HED
recommends
that
the
residential
turf
label
(EPA
Reg.
No.
8660
85)
be
changed
to
specify
only
one
application
per
year
and
to
required
the
product
to
be
watered
in
to
turf
immediately
after
application.
The
exposure
scenarios
and
risk
estimates
are
summarized
below.
Summary
of
Postapplication
Exposure
Scenarios
and
Risk
Estimates
Exposure
Scenario
Route
of
Exposure
Population
Short
Term
MOE
using
DAT
0
TTR
Data
from
Turf
Study
a
Short
Term
MOE
using
DAT
2
TTR
Data
from
Turf
Study
a
Short
Term
MOE
using
HED
Residential
SOPs
a
Cancer
Risk
Estimate
b
High
Contact
Activities
Playing
or
Working
on
Lawns
or
Turf
Dermal
Adult
71
890
N/
A
8.
36E
07
Toddler
42
530
N/
A
N/
A
Low
Contact
Activity
Mowing
Dermal
Adult
2100
26,000
N/
A
5.
73E
08
Low
Contact
Activity
Golf
Course
Reentry
Dermal
Adult
1000
13,000
N/
A
1.
15E
08
Incidental
Hand
toMouth
Activity
(Finger
Licking)
Oral
Toddler
N/
A
N/
A
380
N/
A
Incidental
Object
toMouth
Activity
(Turfgrass
Mouthing)
Oral
Toddler
N/
A
N/
A
1500
N/
A
Incidental
Ingestion
of
Soil
Oral
Toddler
N/
A
N/
A
113,000
N/
A
Combined
Postapplication
Exposures
Incidental
Oral
NonDietary
Oral
Toddler
N/
A
N/
A
300
N/
A
Dermal
&
Incidental
Oral
Oral
&
Dermal
Toddler
N/
A
N/
A
37
N/
A
a
Short
term
Margin
of
Exposure.
MOEs
that
are
<
300
are
of
concern
for
short
term
exposures
and
are
shown
in
bold.
N/
A
=
Not
Applicable.
b
The
HED
endeavors
to
reduce
estimated
cancer
risks
for
the
general
population
to
less
than
one
in
one
million
(10
6
).
N/
A
=
Not
Applicable.
10
Pronamide:
Residential
Exposure/
Risk
Characterization
1.
BACKGROUND
1.1
Purpose
This
document
is
intended
to
support
the
development
of
the
Pronamide
Tolerance
Reassessment
Eligibility
Decision
(TRED)
document
and
includes
the
results
of
HED's
review
of
the
potential
human
health
effects
associated
with
non
dietary
exposure
to
pronamide.
This
is
a
preliminary
exposure
and
risk
assessment.
HED
has
determined
that
there
is
a
potential
for
exposure
in
occupational
settings
from
handling
pronamide
products
during
the
application
process
(i.
e.,
mixer/
loader,
applicator
and
mixer/
loader/
applicator)
and
from
entering
previously
treated
areas.
As
a
result,
risk
assessments
would
normally
have
been
completed
for
occupational
handler
and
postapplication
scenarios.
However,
for
pronamide
the
occupational
handler
and
postapplication
scenarios
will
not
be
assessed,
since
the
assessment
is
only
for
a
TRED
document.
The
assessment
is
limited
to
registered
non
occupational
postapplication
(residential
and
recreational)
uses
of
pronamide,
i.
e.
residential/
recreational
turf
only.
Pronamide
is
a
restricted
use
pesticide,
and
therefore
requires
professional
applicators.
1.2
Criteria
for
Conducting
Exposure
Assessments
A
residential
exposure
assessment
is
required
for
an
active
ingredient
(ai)
if
(1)
certain
toxicological
criteria
are
triggered
and
(2)
there
is
potential
exposure
to
handlers,
such
as
mixers,
loaders
and
applicators
during
use
or
to
persons
entering
treated
sites
after
application
is
complete.
Pronamide
meets
the
criteria,
because
of
the
potential
for
postapplication
residential
exposure
to
residues
on
turf.
Therefore,
a
residential
risk
assessment/
characterization
was
completed
for
this
chemical.
Non
occupational
(residential/
public)
handler
exposures
are
not
expected,
since
all
pronamide
products
are
labeled
as
restricted
use
pesticides.
Postapplication
exposures
to
pronamide
residues
are
anticipated
to
be
short
term
(one
to
30
days)
in
duration
for
residential
scenarios,
since
pronamide
specific
data
show
that
turf
transferrable
residues
decline
to
less
than
the
limit
of
quantification
by
day
14
after
application
(see
Table
4.).
1.3
Summary
of
Toxicity
Concerns
Relating
to
Residential
Exposures
Toxicological
Endpoints
The
toxicological
endpoints
(effects),
the
doses
and
the
uncertainty
factors
that
were
used
to
complete
this
assessment
are
summarized
in
Table
1
below
in
order
to
provide
a
quick
reference
to
the
residential
post
application
exposure
assessments
(based
on
the
November
1,
2001,
HIARC
Report).
11
Table
1.
Toxicological
Endpoints
for
Assessing
Residential
Risks
for
Pronamide.
Exposure
Scenario
Study
Dose
Absorption
Endpoint
UF
&
FQPA/
Target
MOE
Short
term
Dermal
&
Inhalation
Chronic
Toxicity/
Carcinogenicity
in
Rats
Oral
NOAEL
8.46
mg/
kg/
day
100%
of
oral
Increased
liver
weight
&
nonneoplastic
histologic
changes
in
liver,
thyroid
&
ovaries
300
Intermediateterm
Dermal
&
Inhalation
300
Long
term
Dermal
&
Inhalation
300
Short
term
Incidental
Oral
Ingestion
N/
A
300
Intermediateterm
Incidental
Oral
Ingestion
N/
A
300
Lifetime
Cancer
Risk
[All
Populations]
Chronic
Toxicity/
Carcinogenicity
in
Rats
&
Carcinogenicity
in
Mice
Q1
*
=
0.0259
(mg/
kg/
day)
1
N/
A
Benign
testicular
interstitial
cell
tumors
&
uncommon
thyroid
follicular
cell
adenomas
in
rats;
Hepatocellular
carcinoma
in
mouse
N/
A
Acute,
Short
term,
Intermediate
term,
and
Long
term
Endpoints:
Pronamide
is
classified
as
category
III
for
acute
dermal
and
inhalation
toxicity
and
primary
eye
irritation,
category
IV
for
acute
oral
toxicity
and
for
primary
skin
irritation.
Pronamide
is
not
a
skin
sensitizer.
For
short
term
(1
30
days)
incidental
oral
exposures
an
adjusted
dose
of
8.46
mg/
kg/
day
was
established
for
use
in
this
risk
assessment.
This
dose
is
derived
from
the
no
observed
adverse
effect
level
(NOAEL)
from
a
chronic
toxicity/
carcinogenicity
study
in
rats,
where
the
effects
are
increased
liver
weight
and
non
neoplastic
histologic
changes
in
liver,
thyroid,
and
ovaries
observed
at
the
lowest
observed
adverse
effect
level
(LOAEL)
of
42.6
mg/
kg/
day.
The
dose
selection
is
based
on
a
maternal
toxicity
NOAEL
of
5
mg/
kg/
day
and
clinical
signs
of
toxicity
(soiled
anal
area
and
anorexia)
and
liver
effects
(punctate
vacuolation
of
hepatocytes)
observed
at
the
LOAEL
of
20
mg/
kg/
day
in
the
developmental
toxicity
study
conducted
in
rabbits.
Although
this
study
is
of
the
appropriate
route
(oral)
and
duration
(13
days),
the
NOAEL
(5
mg/
kg/
day)
in
this
study
is
lower
than
the
NOAEL
(8.46
mg/
kg/
day)
established
in
the
chronic
12
toxicity/
carcinogenicity
study
in
the
rat.
The
apparent
disparity
between
these
NOAELs
is
driven
by
the
doses
of
pronamide
selected
for
testing
in
these
studies.
The
HIARC
concluded
that
using
a
more
realistic
NOAEL
of
8.46
mg/
kg/
day,
rather
than
5
mg/
kg/
day,
would
provide
a
sufficiently
protective
dose
for
risk
assessment.
The
NOAEL
of
3
mg/
kg/
day
established
in
the
special
thyroid
study
conducted
in
male
rats
was
also
considered.
However
this
dose
was
not
selected
because
the
wide
gap
between
the
NOAEL
(3
mg/
kg/
day)
and
the
LOAEL
(67
mg/
kg/
day)
in
this
study
resulted
in
the
3
mg/
kg/
day
dose
(NOAEL)
being
artificially
low.
In
addition,
the
LOAEL
of
67
mg/
kg/
day
is
comparable
to
the
LOAEL
(56
mg/
kg/
day)
established
in
the
chronic
toxicity
/carcinogenicity
study
conducted
in
rats.
For
short
term
(1
30
days)
dermal
exposures
the
same
oral
dose
and
endpoint
was
selected
for
risk
assessment,
i.
e.
8.46
mg/
kg/
day.
A
dermal
absorption
factor
is
needed,
since
the
endpoint
is
based
on
a
study
using
oral
dosing.
A
default
dermal
absorption
factor
of
100%
relative
to
oral
absorption
was
chosen
by
the
HIARC,
since
the
dermal
absorption
study
sent
to
the
Agency
was
classified
as
unacceptable
and
no
dermal
toxicity
studies
were
submitted.
Uncertainty
Factor
(UF):
The
short
term
dermal
and
oral
incidental
endpoints
have
a
10x
UF
for
intra
species
variability
and
a
10x
UF
for
inter
species
extrapolation.
In
a
memo
dated
December
19,
2001,
the
FQPA
Safety
Factor
Committee
recommended
that
the
FQPA
safety
factor
be
reduced
to
3x.
The
FQPA
Committee
determined
that
the
safety
factor
is
necessary
when
assessing
the
risk
posed
by
pronamide
because
of
evidence
of
endocrine
effects.
The
FQPA
safety
factor
is
required
for
all
population
subgroups
when
assessing
residential
exposures
of
all
durations.
Total
uncertainty
factor
applied
to
short
term
residential
exposures
is
300x.
Carcinogenicity:
In
accordance
with
the
Agency's
Proposed
Guidelines
for
Carcinogen
Risk
Assessment
(September
30,
1992),
the
HED
Carcinogenicity
Peer
Review
Committee
(CPRC)
classified
pronamide
as
a
Group
B2
chemical
(probable
human
carcinogen
with
inadequate
evidence
in
humans).
This
decision
was
based
on
the
finding
of
two
types
of
tumors
in
the
rat
(benign
testicular
interstitial
cell
tumors
and
uncommon
thyroid
follicular
cell
adenomas),
and
one
type
of
tumor
in
the
mouse
(hepatocellular
carcinomas).
A
linear,
low
dose
approach
(Q1
*
)
is
used
for
human
risk
characterization.
The
most
potent
unit
risk
Q1
*
,
based
on
male
mouse
liver
adenoma
and/
or
carcinoma
combined
tumor
rates,
is
2.59
x
10
2
(mg/
kg/
day)
1
in
human
equivalents
[converted
from
animal
to
humans
by
use
of
the
(mg/
kg
body
weight)
3/
4
interspecies
scaling
factor].
Therefore,
the
Hazard
Identification
Assessment
Review
Committee
(HIARC)
recommended
that
a
cancer
risk
assessment
be
conducted
for
pronamide
(November
6,
2001).
1.4
Incident
Reports
A
review
of
incident
data
sources
was
conducted
for
pronamide
on
August
10,
2001
by
J.
Blondell.
1
Only
one
exposure
incident
to
pronamide
was
reported
to
Poison
Control
Centers
from
1993
through
1998.
Cases
involving
exposures
to
multiple
products
were
excluded.
No
cases
were
reported
among
children
under
six
years
of
age
or
among
older
children
and
adults
13
exposed
at
their
workplace.
There
was
one
non
occupationally
exposed
case
among
older
children
and
adults
which
was
not
reported
to
have
symptoms
related
to
their
exposure
and
was
not
seen
in
a
health
care
facility.
Detailed
descriptions
of
two
cases
submitted
to
the
California
Pesticide
Illness
Surveillance
Program
(1982
1999)
were
reviewed.
In
the
first
case,
a
worker
applied
pronamide
product
on
the
ground
for
ten
days
and
reported
malaise,
anorexia,
fatigue,
dizziness,
nausea,
and
vomiting.
In
the
second
case,
one
of
two
workers
moved
an
irrigation
pipe
in
a
field
and
later
reported
dizziness,
vomiting,
and
weakness.
Both
cases
were
categorized
as
`possible',
meaning
the
pronamide
exposure
was
a
possible
cause
of
the
reported
symptoms.
On
the
list
of
the
top
200
chemicals
for
which
the
National
Pesticide
Telecommunications
Network
(NPTN)
received
calls
from
1984
1991,
inclusively,
pronamide
was
not
reported
to
be
involved
in
human
incidents.
In
summation,
very
few
illness
cases
have
been
reported
due
to
pronamide
and
none
have
been
confirmed.
No
recommendations
can
be
made
on
the
very
limited
incident
data
available
for
this
pesticide.
1.5
Summary
of
Use
Patterns
and
Formulations
Pronamide
products
are
described
in
this
section.
Additionally,
available
information
that
describes
the
manner
in
which
pronamide
products
are
applied
is
provided
in
this
section
(e.
g.
use
categories/
sites,
application
methods
and
application
rates).
i.
End
Use
Products
Pronamide
was
manufactured
by
Rohm
&
Haas,
but
has
been
recently
sold
to
Dow
AgroSciences.
One
additional
registrant,
Pursell
Incorporated,
maintains
a
registration
on
one
end
use
product.
Based
on
a
review
(7/
25/
01)
of
the
Office
of
Pesticide
Programs
Reference
Files
System
(REFS)
these
two
registrants
supported
13
registrations
of
four
products
containing
the
active
ingredient
pronamide,
including
one
technical
product,
one
formulation
intermediate,
two
section
3
registration
end
use
products,
and
nine
section
24(
c)
state
registration
labels.
All
end
use
products
are
wettable
powders
packaged
in
water
soluble
pouches.
Table
2:
Active
Labels
for
Pronamide.
Formulation
Percent
Active
Ingredient
EPA
Registration
Number
Technical
92%
707
113
Formulation
Intermediate
51%
707
98
Wettable
Powder
51%
707
159;
CO99001000
14
Wettable
Powder
50%
8660
85;
AZ79003600;
CA86006500;
FL91000700;
ID91001600;
OR90000400;
OR99000700;
OR99000800;
WA91004300
ii.
Mode
of
Action
and
Targets
Controlled
Pronamide
(3,5
dichloro
N(
1,1
dimethyl
2
propynyl)
benzamide)
is
a
selective
pre
and
postemergent
herbicide
used
to
control
grasses
and
broadleaf
weeds.
It
is
a
systemic
herbicide
with
uptake
by
susceptible
weeds
occurring
through
the
roots.
Therefore,
to
be
effective,
pronamide
is
applied
to
the
soil
and
transported
by
water
into
the
root
zone.
Applications
are
made
in
the
late
Fall
and/
or
late
Winter.
iii.
Registered
Use
Categories
Based
on
available
pesticide
usage
information
for
1991
through
2000
supplied
from
the
Biological
and
Economic
Analysis
Division
(BEAD)
Quantitative
Usage
Analysis
(QUA)
for
Pronamide,
dated
September
26,
2001,
total
annual
domestic
usage
of
pronamide
is
approximately
225,000
pounds
active
ingredient
(a.
i.).
In
terms
of
pounds
a.
i.,
total
usage
is
allocated
mainly
to
head
lettuce
(29%),
other
lettuce
(19%),
seed
crops
(13%),
fallowland
(11%),
hay
other
than
alfalfa
(8%),
horticulture
(3%)
and
alfalfa
(3%).
Sites
with
5%
or
more
of
acreage
treated
include
lettuce
other
than
head
lettuce
(49%),
head
lettuce
(36%),
California
endive/
escarole
(31%),
artichokes
(21%),
blackberries
(6%)
and
raspberries
(5%).
Rates
per
application
and
rates
per
year
are
each
generally
less
than
2
pounds
a.
i.
per
acre
for
agricultural
sites.
States
with
significant
usage
in
terms
of
pounds
a.
i.
include
Arizona,
California,
Oregon
and
Washington.
There
is
one
label
used
exclusively
for
occupational
use
on
commercial
sites,
i.
e.
EPA
Reg.
No.
707
159.
Use
sites
on
this
label
include
stone
fruits,
pome
fruits,
grapes,
artichokes,
berries,
forages,
leafy
greens,
winter
peas,
Christmas
trees,
ornamentals,
turf,
rangeland,
and
fallow
land.
Another
label
is
used
exclusively
by
commercial
applicators
on
residential/
recreational
bermudagrass
turf,
i.
e.
EPA
Reg.
No.
8660
85.
Use
sites
on
this
label
include
bermudagrass
lawns,
playing
fields,
and
golf
courses.
There
are
several
active
24C
state
labels.
However,
for
risk
assessment
purposes
the
use
sites
and
use
patterns
on
these
24C
labels
are
covered
by
EPA
Reg.
No.
707
159.
iv.
Application
Parameters
Application
parameters
are
generally
defined
by
the
physical
nature
of
the
use
site,
the
physical
nature
of
the
formulation
(e.
g.,
form
and
packaging),
by
the
equipment
required
to
deliver
the
chemical
to
the
use
site,
and
by
the
application
rate
required
to
achieve
an
efficacious
dose,
along
with
seasonal
limits
to
applications.
Table
3
contains
the
crops,
application
types
and
rates
for
pronamide.
15
Table
3:
Use
Parameters
for
Pronamide
EPA
Reg.
No.
Formulation
Restrictions/
Limitations,
etc.
Use
Sites
Max
App
Rate
in
lb
a.
i./
A
Max.
#
of
Apps
per
Crop
Cycle
or
Year
Min
Interval
(Days)
Reentry
Interval
(Hours)
App
Timing
App
Method
Type
App
Equipment
707
159
51%
W
(3
x
1
lb
water
soluble
pouches)
Restricted
Use
Pesticide.
Do
not
apply
this
product
through
any
type
of
irrigation
system.
Hand
spray
applications
may
be
made
only
to
ornamentals
&
nursery
stock
of
ornamentals.
Apple,
Apricot,
Artichoke
Globes
(CA
only),
Cherry,
Grape,
Nectarine,
Peach,
Pear,
Plum,
Prune.
Blackberry,
Boysenberry,
Raspberry
(Black
&
Red).
Alfalfa,
Blueberry,
Chicory,
Christmas
Trees,
Clover,
Birdsfoot
Treefoil,
Crown
Vetch,
Endive
(Escarole),
Lettuce,
Radicchio,
Rhubarb
(OR
&
WA
only),
Sainfoin,
Woody
Ornamentals,
Nursery
Stock
of
Ornamentals.
Grasses
(Ornamental)
Grown
for
Seed
or
Turf,
Winter
Peas
(ID,
OR
&
WA
only).
Conservation
Reserve
Program
(CRP)
Established
Grass
Stands,
CRP
Fallow
land,
Fallow
land.
4.08
3.06
2.04
1.53
0.51
1
(Fruits);
2
Arti
choke)
1
1
1
1
NS
NS
NS
NS
NS
24
24
24
24
24
Preemergence
&
early
post
emergence
control
of
winter
annual
&
perennial
grasses
&
chickweed
&
preemergence
control
only
of
certain
other
grasses.
Treatments
mainly
in
fall,
and
some
in
winter.
Fruits
by
band
treatment
&
directed
spray.
Berries
by
band
treatment
&
broadcast.
Forages
by
broadcast
&
soil
incorporation.
Leafy
greens
by
band
treatment,
low
volume
spray,
broadcast
&
soil
incorporation.
Turf
&
Grasses
by
broadcast,
band
treatments
&
directed
sprays.
Fruits,
berries,
forages,
chicory,
artichoke,
fallow
land
&
ornamentals
by
low
pressure
ground
sprayer.
Alfalfa,
chicory,
endive
&
lettuce
by
soil
incorporation.
Artichoke,
Christmas
trees,
endive,
fallow
land
&
lettuce
by
aircraft.
Ornamentals
by
hand
held
sprayer.
8660
85
50%
W
(6
x
8
oz
water
soluble
pouches)
Restricted
Use
Pesticide.
Not
for
use
on
turf
being
grown
for
sale
or
other
commercial
use
as
sod,
or
for
commercial
seed
production
or
for
research
purposes.
Bermudagrass
Lawns,
Playing
Fields,
&
Golf
Courses
(Not
recommended
on
greens.).
1.
5NS
NS
NS
Preemergence
&
early
post
emergence
control
of
Poa
annua
in
the
fall
or
late
winter.
Broadcast
Sprayer
OR90000
400
50%
W
Same
as
EPA
Reg.
No.
707
159
Sugarbeets
1.
02NS
NS
NS
Fall
&
E
arly
Winter
Broadcast
Sprayer
EPA
Reg.
No.
Formulation
Restrictions/
Limitations,
etc.
Use
Sites
Max
App
Rate
in
lb
a.
i./
A
Max.
#
of
Apps
per
Crop
Cycle
or
Year
Min
Interval
(Days)
Reentry
Interval
(Hours)
App
Timing
App
Method
Type
App
Equipment
16
CO99001
000
50%
W
Same
as
EPA
Reg.
No.
707
159
Alfalfa
2.
04
NS
NS
24
Fall,
Winter,
Spring
Broadcast
&
soil
incorporated.
Ground,
low
pressure
ground
sprayer,
soil
incorporated.
ID910016
00
50%
W
Same
as
EPA
Reg.
No.
707
159
Blackberries
&
Raspberries
3.06
1
NS
24
Fall
&
Winter
Band
treatment
&
broadcast
Low
pressure
ground
sprayer.
WA9100
4300
50%
W
Same
as
EPA
Reg.
No.
707
159
Christmas
Tree
Plantations
2.04
NS
NS
24
Fall
Band
treatment
&
broadcast
Aircraft
&
low
pressure
ground
sprayer.
AZ79003
600
50%
W
Same
as
EPA
Reg.
No.
707
159
Lettuce
&
Endive
(Escarole)
2.04
1
for
Lettuce
NS
for
Endive
NS
24
Fall
&
Winter
Band
treatment,
low
volume
spray,
broadcast
&
soil
incorporation.
Aircraft,
low
pressure
ground
sprayer,
&
soil
incorporation.
CA86006
500
50%
W
Same
as
EPA
Reg.
No.
707
159
Lettuce
1.53
1
NS
24
Fall
&
Winter
Band
treatment,
low
volume
spray,
broadcast
&
soil
incorporation.
Aircraft,
low
pressure
ground
sprayer,
&
soil
incorporation.
OR99000
700
50%
W
Same
as
EPA
Reg.
No.
707
159
Grasses
grown
for
Seed
0.3825
1
NS
24
Fall
&
Winter
Broadcast
Ground
&
low
pressure
ground
sprayer.
OR99000
800
50%
W
Same
as
EPA
Reg.
No.
707
159
Grasses
grown
for
Seed
0.255
1
NS
24
Fall
&
Winter
Broadcast
Ground
&
low
pressure
ground
sprayer.
FL91000
700
50%
W
Same
as
EPA
Reg.
No.
707
159
Gladiolus
2.
0
4
NS
24
Preemergence
Ground
spray
Low
pressure
ground
sprayer.
ID910016
00
50%
W
Same
as
EPA
Reg.
No.
707
159
Raspberry
(Red
&
Black)
3.
06
1
NS
24
Fall
&
Winter
Band
treatment
&
broadcast
Sprayer
ai
=
active
ingredient;
NS
=
Not
Specified
WP
=
Wettable
Powder
17
2.0
RESIDENTIAL
AND
OTHER
NON
OCCUPATIONAL
EXPOSURES
AND
RISKS
This
assessment
for
pronamide
reflects
the
HED's
current
approaches
for
completing
residential
exposure
assessments
based
on
the
guidance
provided
in
the
Draft:
Series
875
Occupational
and
Residential
Exposure
Test
Guidelines,
Group
B
Postapplication
Exposure
Monitoring
Test
Guidelines,
the
Draft:
Standard
Operating
Procedures
(SOPs)
for
Residential
Exposure
Assessment,
the
Overview
of
Issues
Related
to
the
Standard
Operating
Procedures
for
Residential
Exposure
Assessment
presented
at
the
September
1999
meeting
of
the
FIFRA
Scientific
Advisory
Panel
(SAP),
and
the
Revised
SOPs
(February
2001)
for
Residential
Exposure
Assessment
6,5,
3
.
The
HED
is,
however,
currently
in
the
process
of
revising
its
guidance
for
completing
these
types
of
assessments.
Modifications
to
this
assessment
shall
be
incorporated
as
updated
guidance
becomes
available.
This
will
include
expanding
the
scope
of
the
residential
exposure
assessments
by
developing
guidance
for
characterizing
exposures
from
other
sources
not
already
addressed,
such
as
from
spray
drift;
residential
residue
track
in;
exposures
to
farm
worker
children;
and
exposures
to
children
in
schools.
2.1
Methods
of
Estimating
Non
Cancer
Risks
And
Calculating
Exposures
The
exposures
that
were
calculated
below
represent
the
amount
of
pronamide
that
can
be
deposited
on
the
surface
of
the
skin
after
application,
or
that
can
be
attributed
to
the
mouthing
behaviors
of
children
after
contact
with
treated
turf.
The
HED
calculates
dose
levels
using
the
following
formula:
Where:
Daily
Dose
=
the
amount
as
absorbed
dose
received
from
exposure
to
a
pesticide
in
a
given
scenario
(mg
pesticide
active
ingredient/
kg
body
weight/
day);
Daily
Exposure
=
the
amount
of
dermal
(on
the
skin),
or
nondietary
ingestion
(from
mouthing
behaviors
of
children)
exposure
(mg
pesticide
active
ingredient/
day);
Absorption
Factor
=
a
measure
of
the
flux
or
amount
of
chemical
that
crosses
a
biological
boundary
(%
of
the
total
available);
and
Body
Weight
=
body
weight
determined
to
represent
the
population
of
interest
in
a
risk
assessment
(kg).
For
pronamide,
the
average
body
weight
for
adults
used
in
all
residential
exposure
assessments
is
70
kg,
which
represents
the
general
population.
Although
the
short
term
dermal
endpoint
is
from
a
developmental
study,
the
effect
is
clinical
signs
and
liver
toxicity,
not
developmental
18
toxicity.
The
average
body
weight
used
in
all
assessments
for
1
6
year
old
children
is
15
kg,
based
on
the
SOPs
for
Residential
Exposure
Assessment.
A
100%
dermal
absorption
factor
is
applied
to
the
oral
NOAEL
used
for
dermal
risk
estimates
(i.
e.
dermal
and
oral
absorption
are
equivalent),
since
the
dermal
absorption
study
sent
to
the
Agency
was
classified
as
unacceptable
and
no
dermal
toxicity
studies
were
submitted.
For
oral
exposures
for
children,
the
oral
NOAEL
of
8.46
mg/
kg/
day
for
general
population
is
used.
HED
expresses
non
cancer
risk
estimates
for
residential
exposures
to
pesticides
as
a
Margin
of
Exposure
(MOE).
The
NOAEL
and
the
combined
uncertainty
factors
that
apply
to
all
pronamide
risk
estimates
are
listed
in
Section
1.3,
Table
1.
The
non
occupational
short
term
target
MOE
is
300.
MOEs
were
calculated
using
the
following
formula:
Where:
MOE
=
margin
of
exposure
or
ratio
of
endpoint
of
concern
to
the
chemical
exposure;
Absorbed
Daily
Dose
=
the
absorbed
dose
received
from
exposure
to
a
pesticide
in
a
given
scenario
(mg
pesticide
active
ingredient/
kg
body
weight/
day);
and
NOAEL
=
the
highest
dose
level
in
a
toxicity
study
where
no
observed
adverse
effects
occur
(mg
pesticide
active
ingredient/
kg
body
weight/
day).
In
order
for
the
Agency
to
make
more
informed
risk
management
decisions,
MOEs
can
be
added
together
in
order
to
look
at
the
combined
exposures
that
occur
for
an
individual
if
the
toxic
effect
for
each
route
of
exposure
(e.
g.,
to
the
skin
and
being
ingested)
is
the
same.
For
example,
combining
dermal
and
oral
non
dietary
ingestion
MOEs
for
children
is
of
interest
because
these
exposures
can
occur
at
the
same
time.
The
equation
the
HED
uses
to
add
MOEs
together
is
presented
below:
MOE
total
=
1/((
1/
MOE
a)
+
(1/
MOE
b)
+....
(1/
MOE
n))
Where:
MOE
a,
MOE
b,
and
MOE
n
represent
MOEs
for
each
exposure
route
of
concern
Children's
dermal
high
contact
exposures
to
pronamide
on
treated
lawns
were
combined
with
hand
to
mouth
exposure,
as
these
events
are
likely
to
coincide.
19
2.2
Residential
Handler
Exposures
and
Risks
2.2.1
Residential
Handler
Exposure
Scenarios,
Data,
and
Assumptions
All
pronamide
end
use
products
are
labeled
as
restricted
use
pesticides.
Therefore,
residents
are
restricted
from
handling
pronamide
products.
2.3
Non
Occupational
Postapplication
Exposure
and
Risk
Estimates
When
the
pronamide
RED
document
was
completed
in
May,
1994,
the
Agency
did
not
have
the
data
to
make
a
reregistration
decision
on
pronamide
for
use
on
residential
lawns.
An
estimate
of
risk
was
not
feasible
because
of
numerous
uncertainties
in
potential
exposure
levels,
especially
for
children.
In
the
1994
RED
document,
regulatory
decisions
concerning
postapplication
reentry
to
residential
lawns
were
postponed
until
after
the
submittal
and
review
of
studies
required
to
support
the
residential
lawn
use;
i.
e.
foliar
dislodgeable
dissipation
(old
guideline
132
1(
a)
or
new
guideline
875.2100)
and
dermal
passive
dosimetry
(old
guideline
133
3
or
new
guideline
875.2400).
In
the
interim
since
1994,
a
turf
transferrable
residue
(TTR)
study
was
submitted,
reviewed,
and
found
acceptable
and
useful
for
some
aspects
of
risk
assessment.
The
study
provided
the
required
residue
dissipation
data.
The
methodology
used
to
determine
turf
transferability
(i.
e.
the
modified
California
roller
method)
does
not
match
the
Agency's
current
methodology
(i.
e.
Jazzercise
and
the
California
roller
method)
used
to
determine
the
dermal
transfer
coefficient
on
turf.
Note,
that
the
Outdoor
Residential
Exposure
Task
Force
(ORETF)
is
currently
funding
a
study
which
is
intended
to
provide
con
current
TTR
and
transfer
coefficient
data
for
a
surrogate
chemical.
The
requirement
for
a
dermal
passive
dosimetry
study
remains
outstanding.
However,
the
Agency
can
perform
an
adequate
risk
assessment
to
estimate
risk
on
residential
lawns
by
using
dissipation
data
from
the
TTR
study
in
conjunction
with
the
transferability
assumptions
and
equations
found
in
the
Agency's
residential
SOPs.
2.3.1
Postapplication
Exposure
Scenarios,
Data,
and
Assumptions
Adults
and
children,
are
potentially
exposed
to
pronamide
residues
after
application
of
pronamide
products
in
residential
settings.
After
application
to
turf,
short
term
dermal
exposures
are
anticipated
for
adults
and
children.
Incidental
oral
exposure
is
also
expected
to
occur
for
small
children
and
is
combined
with
their
dermal
exposures,
where
applicable
(i.
e.,
playing
on
turf).
Representative,
range
finding
activities
include
working
and
playing
on
turf,
mowing,
golfing,
and
incidental
ingestion
by
children.
Therefore,
the
pronamide
post
application
exposure/
risk
assessment
contains
exposure
scenarios
in
each
category.
The
physical,
behavioral,
and
physiological
differences
between
adults
and
children
are
continuously
being
studied
by
the
Agency
and
many
others,
and
the
current
standard
assumptions
set
forth
by
the
HED
and
the
Science
Advisory
Panel
(SAP)
are
contained
in
the
aforementioned
Residential
SOPs.
The
SOPs
were
updated,
in
February,
2001,
to
reflect
the
latest
research
findings
and
refined
assessment
strategies
since
the
presentation
to
the
SAP
in
September
1999.
20
Wherever
available,
reported
usage
data
are
used
in
this
process
to
define
values
such
as
application
rates
and
application
frequency.
Only
one
end
use
product
label
can
be
used
in
a
residential
setting.
This
residential
label
(EPA
Reg.
No.
8660
85)
indicates
a
maximum
application
rate
of
1.5
lb
ai/
acre
for
pre
emergence
applications
by
lawn
care
operators
(LCOs)
to
lawns,
playing
fields,
and
golf
courses
as
a
single
application.
The
maximum
application
rate
for
post
emergence
applications
is
1.0
lb
ai/
acre.
The
label
indicates
that
typical
application
rates
for
pre
and
post
emergence
applications
are
at
0.5
to
1.0
lb
ai/
acre,
with
the
maximum
rate
being
used
in
areas
of
heavy
growth
weeds.
This
residential
label
does
not
specify
or
restrict
the
number
of
applications
allowed
per
year
to
turf.
However,
the
agricultural
label
(EPA
Reg.
No.
707
159)
allows
only
one
application
per
year
to
grasses
grown
for
turf
or
seed.
For
both
labels,
applications
to
turf
are
only
made
in
the
late
Fall
or
late
Winter.
Therefore,
for
residential
turf,
it
is
reasonable
to
assume
that
typically
only
one
application
is
made,
and
potentially
only
two
applications
would
be
made
in
any
year.
If
two
applications
were
made,
one
would
probably
be
made
in
late
Fall,
followed
by
another
application
in
late
Winter.
Results
from
environmental
fate
studies
indicate
that
pronamide
is
very
persistent
in
soil
and
water
with
half
lifes
of
many
months.
Additionally,
rotational
crop
studies
show
accumulation
in
several
crop
types
at
one,
six
and
twelve
months
after
application.
However,
results
from
a
recent
turf
transferable
residue
(TTR)
study
on
turf
using
pronamide
(i.
e.
MRID
44952501)
indicate
that
the
half
life
of
turf
transferrable
residues
was
slightly
less
than
two
days.
Also,
the
residential
label
(EPA
Reg.
No.
8660
85)
instructs
applicators
to
lightly
irrigate
within
a
day
of
application
if
no
rain
occurs.
Such
irrigation
occurred
at
24
hours
after
application
in
the
TTR
study.
Study
data
showed
that
residues
dissipate
to
below
the
level
of
quantification
by
day
14
following
application.
Therefore,
only
short
term
(i.
e.,
one
day
to
one
month)
exposures
would
be
anticipated,
since
most
of
the
pesticide
should
move
into
the
soil,
and
any
remaining
foliar
residues
should
dissipate
within
a
month.
While
residues
in
soil
could
persist
for
greater
than
30
days,
it
is
unlikely
that
children
will
play
on
or
contact
soil
for
greater
than
30
consecutive
days
during
the
late
Fall
or
late
Winter
months.
MRID
44952501
(Determination
of
Turf
Transferrable
Residue
on
Turf
Treated
with
Kerb®
50W
Herbicide):
Turf
transferable
residues
(TTR)
were
monitored
using
the
Modified
California
Roller
sampling
methodology
for
the
typical
end
use
product
(EPA
Reg.
No.
707
159),
a
wettable
powder
formulation
containing
50
%
active
ingredient
(ai).
The
product
was
applied
at
one
geographically
representative
site
in
North
Carolina
(NC)
with
three
replicated
subplots.
A
single
application
by
ground
sprayer
was
applied
prior
to
monitoring.
The
product
was
applied
once
at
the
label
specified
maximum
application
rate
of
1.5
lb
ai
per
acre
(lb
a.
i./
A).
The
application
was
made
on
September
23,
1998,
which
agrees
with
the
label
specified
application
time
period
of
Fall
or
late
Winter.
Also,
the
treated
plot
was
irrigated
24
hours
after
the
application
(DAT
1;
but
after
samples
were
taken)
with
0.9
inches
of
water
to
move
the
ai
into
the
root
zone.
The
product
label
specifies
that
if
a
rain
event
does
not
occur
within
one
day
after
application,
that
the
site
should
be
lightly
irrigated.
Rain
occurred
prior
to
the
application
of
the
pronamide
and
then
again
on
DAT
7
(0.25
inches)
and
DAT
11
(0.23
inches).
Control
samples
were
taken
prior
to
application
for
background
analyses
and
for
fortification
purposes.
After
application
triplicate
samples
were
collected
at
day
zero
(0)
as
soon
as
the
spray
dried;
at
21
6,
12
and
24
hours
(0.25,
0.5
and
1)
and
2,
4,
7,
10
and
14
days
after
application
treatment
(DAT)
of
the
test
substance.
Samples
were
stored
in
a
freezer
for
15
to
37
days
prior
to
analysis.
Six
replicate
field
fortification
samples
at
each
of
two
levels
(50
and
10,000
µg)
were
prepared
at
sampling
times
DAT
0
and
DAT
14.
Fortification
samples
were
handled
and
stored
the
same
as
treated
samples.
The
results
of
the
TTR
data
(mean
and
coefficient
of
variation)
are
presented
in
Table
4.
Observed
residue
values
exhibited
a
wide
range
of
variability
(i.
e.
6
to137%).
Field
fortification
recoveries
averaged
85.8%
(standard
deviation
6.9%),
indicating
that
pronamide
was
relatively
stable
in
the
sampling
media
during
the
handling
and
storage
periods.
Versar
corrected
these
TTR
data
to
the
nearest
fortification
recovery.
These
data
had
only
minor
deficiencies;
such
as
a
limited
number
of
controls,
a
relatively
high
variance,
and
only
one
site
was
tested;
although
three
sites
are
required
in
the
guidelines.
Since
bermudagrass
is
a
regionally
selective
use
site,
the
employment
of
only
one
test
site
is
acceptable.
The
dissipation
rate
derived
from
these
data
was
relatively
rapid
with
an
estimated
pronamide
half
life
of
1.8
days
in
turf.
Also,
the
data
show
that
the
average
pronamide
residues
found
immediately
after
application
(DAT
0)
was
approximately
one
percent
of
the
target
application.
The
maximum
average
pronamide
residue
found
shortly
after
application
(DAT
0.5)
was
approximately
2.6%
of
the
applied
pronamide
(i.
e.
the
transfer
efficiency),
and
the
overall
average
residue
observed
on
day
zero
after
application
(i.
e.
DAT
0,
DAT
0.25
&
DAT
0.5)
was
approximately
1.65%
of
the
applied
pronamide.
By
comparison,
the
Agency's
SOP
uses
a
transfer
efficiency
(percent
of
application
rate)
of
5%.
These
TTR
data
were
found
to
be
acceptable
for
use
quantitatively
in
the
postapplication
exposure
assessment.
The
HED
used
the
mean
observed
residue
data
from
DAT
0
through
DAT
0.5
from
this
study
to
estimate
short
term
non
occupational
exposures,
since
the
percent
transferred
was
greater
than
one
percent.
However,
the
predicted
TTR
data
are
most
suitable
for
longer
term
exposures.
The
HED
always
completes
short
term
risk
assessments
using
maximum
application
rates
for
each
scenario,
because
what
is
possible
under
the
label
(the
legal
means
of
controlling
pesticide
use)
must
be
evaluated
for
complete
stewardship
in
order
to
ensure
the
HED
has
no
concern
for
the
specific
use.
As
a
result
of
home
lawn
uses,
the
HED
has
concerns
for
potential
postapplication
exposures
to
both
adults
and
children.
Anticipated
routes
of
postapplication
exposure
include
dermal
exposure
to
adults
and
children
(toddlers),
and
incidental
oral
exposure
to
children
(toddlers).
Postapplication
exposures
via
the
inhalation
route
are
not
anticipated,
since
pronamide
is
applied
as
a
liquid,
and
is
a
mobile
systemic
herbicide,
which
when
watered
in
(as
directed
on
the
label)
quickly
moves
into
soil,
where
it
is
rapidly
absorbed
into
vegetation.
Additionally,
the
uses
and
primary
exposures
are
outdoors,
allowing
for
significant
dilution.
Also,
the
vapor
pressure
of
pronamide
is
8.5E
5
mm
Hg
at
25
0
C.
In
order
to
adequately
consider
the
risks
to
children,
the
guidance
from
the
HED's
updated
Residential
SOPs
(2/
01)
was
used
to
address
the
exposures
of
children
contacting
recently
22
treated
turf.
The
SOPs
for
turf
use
a
high
contact
activity
based
on
the
use
of
Jazzercise®
to
represent
the
exposures
of
an
actively
playing
child
or
active
adult.
Lower
contact
activities,
such
as
walking,
mowing,
or
golfing,
for
example,
use
transfer
coefficients
based
on
mowing
and
golfing
studies.
The
HED
believes
that
pronamide
exposures
can
occur
over
a
single
day
or
up
to
a
few
weeks
at
a
time.
This
is
supported
by
the
length
of
time
that
residues
took
to
decline
in
the
pronamide
turf
TTR
study.
The
HED
classifies
these
as
short
term
exposures
(one
day
to
one
month).
No
intermediate
term
(one
to
six
months)
or
long
term
(six
months
or
more)
residential
exposures
are
anticipated
with
the
use
of
pronamide,
due
to
the
product's
use
pattern,
and
since
turf
residues
dissipate
rapidly
to
below
the
limit
of
quantification
by
day
14
following
application
(pronamide
TTR
study),
and
the
short,
intermediate,
and
long
term
endpoints
are
the
same.
These
classifications
are
the
basis
for
selecting
toxicological
endpoints
for
chemicals
and
are
generally
included
in
each
risk
assessment.
Route
specific
(i.
e.,
dermal
and
incidental
oral)
pronamide
exposures
were
combined
where
appropriate
(i.
e.
small
children).
Restricted
entry
intervals
are
not
considered
a
practical
regulatory
tool
for
reducing
exposures
and
risks
in
the
residential
environment
(i.
e.,
for
the
general
population).
Although
LCOs
may
inform
residents
to
stay
off
treated
turf,
or
signs
may
be
posted,
there
is
no
practical
way
to
restrict
access
by
humans
or
pets.
Therefore,
for
chemicals
used
in
the
residential
environment
or
any
other
areas
where
the
general
population
can
be
exposed,
the
HED
currently
considers
the
risks
associated
with
a
chemical
on
the
day
they
are
applied.
Exposure
Scenarios
and
Assumptions:
The
activities
that
were
selected
as
the
basis
for
the
risk
assessment
are
represented
by
the
following
assumptions
and
transfer
coefficients
for
short
term
endpoints:
°
Adults
involved
in
a
low
exposure
activity
on
turf
such
as
golfing
(4
hours
a
day),
mowing
(2
hours
per
day),
or
other
light
work
activities
(2
hours
per
day),
with
a
transfer
coefficient
=
500
cm
2
/hour;
°
Adults
involved
in
a
high
exposure
activity
on
turf
such
as
heavy
yard
work,
gardening
or
laying
sod
for
2
hours
per
day,
with
a
transfer
coefficient
=
14,500
cm
2
/hour;
°
Small
children
involved
in
a
high
exposure
activity
for
2
hours
per
day,
with
a
transfer
coefficient
=
5,200
cm
2
/hour
(based
on
the
recommended
revisions
to
the
SOPs
for
residential
exposure
assessments
(2/
2001));
Small
children's
exposure
levels
were
calculated
for
the
residential
exposure
assessment
and
for
the
purposes
of
completing
an
aggregate
risk
assessment
that
also
considers
exposure
from
dietary
intake
of
food
and
water
(for
all
age
groups).
Dermal
exposure
values
for
adults
and
children
on
the
day
of
treatment
were
calculated
based
on
the
following
equation
(see
Residential
SOP
2.2:
Postapplication
dermal
potential
dose
from
pesticide
residues
on
turf):
23
DE(
t)
(mg/
day)
=
(TTR(
t)
(µg/
cm
2
)
x
TC
(cm
2
/hr)
x
Hr/
Day)/
1000
(µg/
mg)
Where:
DE
=
Dermal
exposure
at
time
(t)
attributable
for
activity
in
a
previously
treated
area
(mg/
day);
TTR
=
Turf
Transferable
Residue
(TTR)
data
(from
MRID
#
44952501,
i.
e.
mean
observed
residue
value
of
0.289
µg/
cm
2
from
day
zero
after
application
(DAT
0)
through
DAT
0.5);
TC
=
Transfer
Coefficient
(cm
2
/hr);
and
Hr
=
Exposure
duration
in
hours.
The
HED's
Residential
SOP
contains
guidance
for
considering
children's
exposure
to
treated
turf.
The
dermal
calculations,
as
noted
above,
were
completed
based
on
the
guidance
provided
in
the
document.
All
nondietary
exposures
were
also
calculated
using
guidance
from
this
document.
Specifically,
the
kinds
of
nondietary
ingestion
exposures
that
were
considered
in
this
assessment
include
the
following:
°
Dose
from
hand
to
mouth
activity
calculated
using
SOP
2.3.2:
Postapplication
dose
among
small
children
from
incidental
nondietary
ingestion
of
pesticide
residues
on
residential
lawns
from
hand
to
mouth
transfer;
°
Dose
from
mouthing
treated
turf
calculated
using
SOP
2.3.3:
Postapplication
dose
among
small
children
from
the
ingestion
of
pesticide
treated
turfgrass;
and
°
Dose
from
incidental
ingestion
of
soil
calculated
using
SOP
2.3.4:
Postapplication
dose
among
small
children
from
the
ingestion
of
soil
in
pesticide
treated
areas.
Hand
to
Mouth
Transfer
(Mouthing)
The
following
demonstrates
the
method
used
to
calculate
exposures
that
are
attributable
to
a
child
touching
treated
turf
and
then
putting
their
hands
in
their
mouth
(SOP
2.3.2):
PDR
=
(AR
*
F
DR
*
CF
*
SA
*
EXT
*
Freq
*
Hr
*
(1
mg/
1000
µg)
where:
PDR
=
potential
dose
rate
(mg/
day)
AR
=
application
rate
(lb
ai/
A)
F
DR
=
fraction
of
dislodgeable
residue
from
turf
for
hand
to
mouth
behavior
with
wet
hands
(5%)
CF
=
conversion
factor
to
convert
lb
ai/
A
to
µg/
cm
2
(11.2)
SA
=
surface
area
of
1
to
3
fingers
(20
cm
2
);
EXT
=
extraction
rate
by
saliva
(50%)
Freq
=
frequency
of
hand
to
mouth
events
(20
events/
hour);
and
Hr
=
exposure
duration
(2
hours)
24
The
surface
area
for
1
3
fingers
used
(20
cm
2
)
is
the
median
surface
area
for
a
small
child
(age
3
years)
as
updated
in
12/
99.
The
frequency
of
hand
to
mouth
events
is
20
events
per
hour
as
updated
in
12/
99.
The
fraction
of
residue
dislodgeable
from
wet
hands
is
five
percent
and
the
extraction
rate
by
saliva
is
fifty
percent
as
updated
in
12/
99.
The
time
spent
outdoors
(2
hours/
day)
is
also
a
recommended
value
from
the
U.
S.
EPA
Exposure
Factors
Handbook.
This
model
for
hand
to
mouth
dose
is
based
on
the
premise
that
a
child
puts
2
3
fingers
in
their
mouth,
five
percent
of
the
residues
on
the
hands
are
transferred
from
the
hands
to
the
mouth,
fifty
percent
of
the
residues
is
extracted
by
saliva
and
that
all
of
the
residues
available
on
the
treated
turf
transfer
to
the
child's
hand
each
time
they
exhibit
this
behavior.
Object
to
Mouth
The
following
illustrates
the
approach
used
to
calculate
exposures
that
are
attributable
to
a
child
mouthing
treated
turf
(SOP
2.3.3):
PDR
=
(AR
*
F
DR
*
CF
*
IgR
*
(1
mg/
1000µg)
where:
PDR
=
potential
dose
rate
(mg/
day);
AR
=
application
rate
F
DR
=
fraction
of
residue
dislodgeable
from
turf
(20%)
CF
=
conversion
factor
to
convert
lb
ai/
A
to
µg/
cm
2
(11.2)
IgR
=
ingestion
rate
for
mouthing
of
grass
per
day
(25
cm
2
/day)
The
ingestion
rate
used
(25
cm
2
/day)
assumes
that
a
child
will
grab
a
handful
of
turf,
mouth
it
and
remove
twenty
percent
pronamide
residues,
and
then
remove
it
from
their
mouth
as
described
in
the
Residential
SOPs.
The
surface
area
of
25
cm
2
/day
is
thought
to
approximate
a
handful
of
turf
that
is
mouthed.
Incidental
Soil
Ingestion
The
following
is
the
formula
used
to
estimate
exposure
from
incidental
ingestion
of
soil
treated
with
pronamide
(SOP
2.3.4):
PDR
=
(AR
*
(1
D)
t
*
IgR
*
CF1
*
CF2
*
CF3
*
CF4)
where:
PDR
=
potential
dose
rate
(mg/
kg/
day)
AR
=
application
rate
(lb
ai/
A)
(1
D)
=
fraction
or
residue
retained
on
uppermost
1
cm
of
soil,
assumed
to
be
100
percent
based
on
soil
incorporation
into
top
1
cm
of
soil
after
application
(1.0/
cm)
t
=
postapplication
day
on
which
exposure
is
being
assessed,
assumed
to
be
day
0
IgR
=
ingestion
rate
of
soil
(100
mg/
day)
CF1
=
weight
unit
conversion
factor
to
convert
the
lbs
ai
in
the
25
application
rate
to
µg
for
the
soil
residue
value
(4.54
x
10
8
µg/
lb)
CF2
=
area
unit
conversion
factor
to
convert
the
surface
area
units
(ft
2
)
in
the
application
rate
to
cm
2
for
the
SR
value
(2.47
x
10
8
acre/
cm
2
if
the
application
rate
is
per
acre)
CF3
=
volume
to
weight
unit
conversion
factor
to
convert
the
volume
units
(cm
3
)
to
weight
units
for
the
SR
value
(0.67
cm
3
/g
soil)
7
CF4
=
weight
unit
conversion
factor
to
convert
the
µg
of
residues
on
the
soil
to
grams
to
provide
units
of
mg/
day
(1E
6
g/
µg)
The
estimated
exposure
from
ingestion
of
soil
from
an
area
treated
with
pesticide
is
a
minor
contributor
to
the
total
incidental
oral
dose.
The
following
specific
assumptions
and
factors
were
used
to
complete
the
exposure
assessment:
°
These
assessments
were
based
on
the
guidance
provided
in
the
Residential
SOPs
and
the
Recommended
Revisions
to
the
SOPs
for
Residential
Exposure
Assessments
(2/
22/
01).
°
To
assess
short
term
dermal
exposures,
the
TTR
value
(0.289
µg/
cm
2
)
was
used
for
turf
on
the
day
of
application
(DAT
0
through
DAT
0.5)
from
the
turf
transferrable
residue
study
(MRID
44952501);
°
Calculations
for
short
term
exposures
are
based
on
the
maximum
application
rate
(1.5
lb
ai/
acre)
for
residential
turf;
°
Due
to
a
lack
of
scenario
specific
exposure
data,
HED
has
calculated
exposure
values
for
adults
using
surrogate
dermal
transfer
coefficients
that
represent
activities
such
as
mowing,
golfing,
and
yardwork.
2.3.2
Postapplication
Exposure
and
Non
Cancer
Risk
Estimates
The
results
of
the
residential
post
application
exposure
and
risk
estimates
are
presented
in
Tables
5
7
in
Appendix
A.
The
dermal
non
cancer
risk
estimates
for
adults
and
children
exposed
to
pronamide
while
doing
activities
on
turf
are
shown
in
Table
5.
The
dermal
cancer
risk
estimates
for
adults
exposed
to
pronamide
while
doing
activities
on
turf
are
shown
in
Table
6.
The
oral
nondietary
non
cancer
risk
estimates
for
small
children
from
hand
to
mouth
and
ingestion
exposure
while
playing
on
pronamide
treated
turf
are
contained
in
Table
7.
For
pronamide
short
term
non
occupational
risks,
the
HED
has
established
a
level
of
concern
for
MOEs
<
300.
Risk
estimates
for
short
term
dermal
contact
with
treated
turf
during
high
contact
lawn
activities
on
day
zero
following
application
(DAT
0)
exceed
HED's
estimated
level
of
concern,
using
residue
data
from
the
TTR
study,
i.
e.
result
in
MOEs
<
300
for
adults
(MOE
=
71)
and
children
(MOE
=
42).
However,
using
DAT
2
residue
data
from
the
TTR
study
yielded
MOEs
that
do
not
exceed
the
level
of
concern
(MOEs
$
300)
for
adults
(MOE
=
890)
and
children
(MOE
=
530)
during
high
contact
lawn
activities.
Note
that
the
test
plots
were
irrigated
immediately
after
the
DAT
1
samples
were
taken,
i.
e.
24
hours
after
application
of
pronamide,
as
specified
on
the
label.
The
data
show
that
watering
in
the
pronamide
product
clearly
alleviates
these
risk
26
concerns.
Risk
estimates
for
adults
for
short
term
dermal
contact
with
residues
on
treated
turf
during
the
low
contact
activities
of
grass
mowing
(MOE
=
2100)
or
golfing
(MOE
=
1000)
on
the
day
of
treatment
do
not
exceed
the
level
of
concern
(MOEs
$
300);
see
Table
5.
HED
also
assessed
short
term
risks
to
small
children
from
incidental
oral
ingestion
of
pronamide
residues
following
application
to
residential
lawns
(see
Table
7).
The
level
of
concern
for
residential
risks
is
set
by
the
HED
at
a
MOE
<
300.
The
risk
calculations
for
small
children's
non
dietary
ingestion
of
pronamide
on
treated
turf
indicate
that
risks
do
not
exceed
the
level
of
concern
(i.
e.
MOEs
$
300)
for
hand
to
mouth
finger
licking
(MOE
=
380),
incidental
ingestion
of
soil
(MOE
=
113,000),
and
incidental
object
to
mouth
(MOE
=
1500).
The
small
children's
combined
oral
hand
to
mouth
scenarios
(MOE
=
300)
also
do
not
exceed
the
level
of
concern.
When
risks
from
dermal
exposures
from
pronamide
to
small
children
are
combined
with
risks
from
incidental
oral
exposures,
the
combined
short
term
risk
estimates
exceed
the
level
of
concern
(MOEs
<
300),
with
an
MOE
at
37.
However,
the
likelihood
of
all
incidental
oral
exposures
co
occurring
with
dermal
exposures
is
low.
2.3.3
Postapplication
Cancer
Risk
Estimates
The
HED
endeavors
to
reduce
estimated
cancer
risks
for
the
general
population
to
less
than
one
in
one
million
(10
6
).
Estimated
adult
cancer
risks
were
calculated
using
the
same
residential
exposure
scenarios
as
described
in
section
2.3.1.
The
lifetime
average
daily
dose
(LADD)
must
be
calculated
by
first
determining
the
dermal
exposure
(DE)
from
foliar
contact
(see
formula
above
in
Section
2.3.1);
i.
e.
DE(
t)
(mg/
day)
=
(TTR(
t)
(µg/
cm
2
)
x
TC
(cm
2
/hr)
x
hr/
day)/
1000
(µg/
mg).
Then,
the
dermal
exposure
is
converted
to
absorbed
daily
dose
multiplied
by
the
frequency
of
exposure
in
days
per
year,
as
follows:
LADD
(mg/
kg/
day)
=
DE/
70
kg
(mg/
kg/
day)
x
absorption
factor
(100%)
x
(exposure
frequency/
365
days
per
year)
x
(50
years
residential
duration/
70
year
lifetime)
and
the
cancer
risk
=
LADD
(mg/
kg/
day)
x
Q1
*
(mg/
kg/
day)
1
Based
on
the
pesticide
label,
a
typical
residential/
recreational
lawn
application
rate
of
1.0
lb/
acre,
with
an
application
frequency
of
once
per
year,
was
assumed
for
the
residential
cancer
risk
assessment.
Pronamide
is
applied
in
the
dormant
season,
which
reduces
the
number
of
contact
days
expected.
A
single
exposure
is
deemed
more
likely,
but
up
to
14
days
exposure
could
occur
based
on
the
residue
dissipation
pattern.
The
14
day
average
turf
residues
from
the
TTR
study
(MRID
44952501)
were
used
(i.
e.
0.07913
F
g/
cm
2
,
when
adjusted
to
a
typical
application
rate
of
1.0
lb
ai/
acre);
since
residues
in
the
TTR
study
dissipated
to
the
level
of
quantitation
by
14
days
after
application.
The
average
residue,
and
an
exposure
frequency
of
one
day
per
year,
or
50
days
in
a
lifetime,
was
assumed
for
high
contact
activities
(e.
g.
playing
and
working
on
lawns
and
turf)
and
low
contact
activities
(e.
g.
mowing
or
golfing).
An
adult
mowing
a
treated
lawn
one
day
each
year
has
a
cancer
risk
of
5.7
x
10
8
.
The
average
golfer
plays
18
times
per
year,
so
one
day's
exposure
is
possible
if
pronamide
is
applied
once
per
year
27
on
average.
These
assumptions
are
not
meant
to
imply
that
exposures
will
occur
for
only
one
day.
The
adult
golfer
cancer
risk
is
estimated
at
1.2
x
10
7
.
An
adult
performing
dermal
high
contact
activities
on
turf
during
the
2
week
period
of
residue
dissipation
has
a
cancer
risk
of
8.4
x
10
7
.
The
HED
endeavors
to
reduce
estimated
cancer
risks
for
the
general
population
to
less
than
one
in
one
million
(10
6
).
In
order
to
exceed
the
cancer
risk
(1.0
x
10
6
),
exposure
frequencies
of
17.5,
8.7
and
1.2
days
per
year
would
be
needed
for
the
activities
of
mowing,
golfing
and
high
contact
work,
respectively.
2.3.4
Summary
of
Postapplication
Risks,
Data
Gaps,
and
Confidence
in
Exposure
and
Risk
Estimates
Residential
exposures
are
anticipated
as
a
result
of
professional
lawn
care
operator
application.
Risk
estimates
were
performed
for
potential
contact
with
lawn
or
soil
treated
with
pronamide,
using
data
from
a
turf
transferable
residue
study
submitted
for
pronamide,
and
using
HED's
Draft
SOPs
for
Residential
Exposure
Assessment.
These
estimates
are
considered
conservative,
but
appropriate,
since
the
study
data
and
risk
estimates
were
generated
at
the
maximum
application
rate.
The
Residential
SOPs
are
considered
to
be
upper
bound
scenarios
for
determining
risk
estimates.
The
adult
and
children's
transfer
coefficients
are
based
on
the
Jazzercise
protocol
and
an
upper
percentile
exposure
duration
value.
Where
study
data
were
used
with
the
SOP
formulae,
these
risk
estimates
were
better
refined,
and
hence,
less
conservative.
Therefore,
the
exposure
estimates
related
to
turf
skin
contact
(which
were
based
on
study
data)
are
more
refined
than
the
estimates
of
incidental
ingestion.
For
postapplication
residential
exposures,
the
scenarios
with
short
term
risk
estimates
that
exceed
HED's
level
of
concern
(MOEs
<
300)
are
the
high
contact
dermal
exposure
activities
(adults
&
toddlers)
of
working
or
playing
on
lawns.
The
scenarios
with
risks
estimates
that
do
not
exceed
HED's
level
of
concern
(MOEs
$
300)
are
as
follows:
1)
the
low
contact
dermal
exposure
activities
of
mowing
lawns
(adults)
and
golfing
(adults)
on
treated
turf;
and
2)
the
incidental
oral
exposure
activities
by
toddlers
of
ingesting
soil,
hand
to
mouth
(finger
licking),
and
object
to
mouth
(turfgrass
mouthing)
while
playing
on
lawns.
Combining
risk
estimates
for
exposure
scenarios
that
are
likely
to
occur
together
resulted
in
risk
estimates
of
greater
concern.
For
example,
it
is
possible
that
the
same
child
could
receive
dermal
exposures
from
performing
high
contact
activities
on
a
lawn,
while
at
the
same
time
receive
incidental
oral
exposures
from
hand
to
mouth,
object
to
mouth
and/
or
soil
ingestion.
Combining
the
postapplication
turf
short
term
risk
estimates
for
the
incidental
oral
nondietary
exposures
to
small
children
resulted
in
a
risk
estimate
(MOE
=
302)
that
does
not
exceed
HED's
level
of
concern
(MOE
<
300).
However,
combining
the
postapplication
turf
dermal
and
incidental
oral
risk
estimates
for
small
children
resulted
in
an
MOE
(MOE
=
37)
that
exceeds
HED's
level
of
concern
(MOEs
<
300);
primarily
due
to
the
dermal
exposure.
However,
the
likelihood
of
all
incidental
oral
exposures
co
occurring
with
dermal
exposures
is
low.
28
2.4
RESIDENTIAL
AND
NON
OCCUPATIONAL
RISK
CHARACTERIZATION
2.4.1
Residential
Handler
Risk
Characterization
All
pronamide
end
use
products
are
labeled
as
restricted
use
pesticides.
Therefore,
residents
are
restricted
from
handling
pronamide
products.
2.4.2
Non
Occupational
Postapplication
Risk
Characterization
The
short
term
residential
exposures
to
treated
lawns
were
based
upon
exposure
to
transferable
residues
at
the
earliest
possible
opportunity
(i.
e.
residues
at
day
zero
after
application),
the
maximum
application
rate,
and
a
100%
dermal
absorption.
While
these
are
high
end
scenarios,
they
are
not
worst
case,
because
the
time
of
exposure
is
short
(i.
e.
2
to
4
hours)
and
risk
estimates
are
based
on
behavioral
data,
actual
field
residue
data
supplied
by
the
registrant,
and
are
generated
using
HED
SOPs.
The
translation
of
a
dose
based
on
a
chronic
effect
for
the
purpose
of
short
term
risk
estimation
also
contributes
to
a
high
end
exposure
estimate.
Mitigating
circumstances
for
residential
exposure
to
pronamide
residues
may
include
the
watering
in
of
the
product
to
turf
immediately
after
application,
instead
of
within
24
hours
after
application,
as
the
label
currently
recommends.
Pronamide
product
was
watered
in
for
the
TTR
study
(MRID
44952501).
This
instruction,
however,
does
not
prevent
contact
with
treated
turf
prior
to
watering
in.
HED
recommends
that
the
residential
turf
label
(EPA
Reg.
No.
8660
85)
be
changed
to
specify
only
one
application
per
year,
and
require
the
product
to
be
watered
into
turf
immediately
after
application.
29
References
1.
Blondell,
J.
Review
of
Pronamide
Incident
Reports,
DP
Barcode
D276935.
EPA.
August
10,
2001.
2.
Hazard
Identification
Assessment
Review
Committee
(HIARC)
Meeting
on
Pronamide.
November
1,
2001.
3.
Recommended
Revisions
to
the
Standard
Operating
Procedures
(SOPs)
for
Residential
Exposure
Assessments.
EPA,
HED
Exposure
SAC,
February
22,
2001.
4.
Outdoor
Residential
Exposure
Task
Force.
Response
to
the
Outdoor
Residential
Exposure
Data
Call
in
Dated:
March
3,
1995.
ORETF.
November
12,
1999.
5.
Draft
SOPs
for
Residential
Exposure
Assessments.
EPA.
December
18,
1997.
6.
[Draft]
OPPTS
Series
875
Occupational
and
Residential
Test
Guidelines:
Group
BPostapplication
Exposure
Monitoring
Test
Guidelines.
EPA.
February
1998
version.
7.
Martin,
D.;
Determination
of
Transferrable
Turf
Residues
on
Turf
Treated
with
Pronamide
(Kerb®
50W
Herbicide).
Rohm
and
Haas
Company;
06/
30/
99;
EPA
MRID
44952501.
30
Appendix
Pronamide
Exposure
and
Risk
Estimates
Tables
4
through
7
31
Table
4.
Summary
of
Postapplication
Turf
Transferable
Residue
Study
MRID
44952501
TTR
on
Turf
Treated
with
Pronamide
(50%
Wettable
Powder
in
Water
Soluble
Pouches)
Study
Application
Rate:
1.5
lb
ai/
acre
Slope
=
0.387;
Intercept
=
1.86;
R
2
=
0.79
DAT
(days)
Mean
Observed
TTR
(µg/
cm
2
)
(CV)
Predicted
TTR
(µg/
cm
2
)
0
0.161
(10.8)
0.155
0.25
0.252
(8.3)
0.5
0.453
(18.0)
Average
of
DAT
0
0.5
0.289
1
0.154
(7.24)
0.105
2
0.023
(48.0)
0.072
4
0.016
(12.8)
0.033
7
0.004
(6.2)
0.010
10
0.002
(38.2)
0.003
14
0.003
(137)
0.0007
Average
of
DAT
0
14
0.1187
0.032
32
Table
5.
Pronamide
Residential
Postapplication
Activities
on
Treated
Turf:
Dermal
Exposure
and
Non
Cancer
Risk
Estimates
Short
term
Risk
Estimates
at
DAT
0
using
TTR
Data
from
Turf
Study
Short
term
Risk
Estimates
at
DAT
2
using
TTR
Data
from
Turf
Study
Activity
Transfer
Coefficient
(cm
2
/hr)
(a)
TTR
µg/
cm
2
DAT
0
(b)
Dermal
Dose
(mg/
kg/
day)
(c)
MOE
(d)
TTR
µg/
cm
2
DAT
2
(b)
Dermal
Dose
(mg/
kg/
day)
(c)
MOE
(d)
high
contact
lawn
activities:
adults
14,500
0.2886
0.1196
71
0.023
0.00953
890
high
contact
lawn
activities:
toddler
5,200
0.2886
0.2001
42
0.023
0.0159
530
mowing
turf:
adults
500
0.2886
0.00413
2100
0.023
0.000329
26,000
golf
course
reentry:
adult
500
0.2886
0.00825
1000
0.023
0.000657
13,000
a
Transfer
coefficients
from
the
Residential
SOP's
(02/
01).
b
TTR
Source:
MRID
#
44952501
turf
transferable
residue
study
see
Table
4
for
raw
data
and
regression
statistics.
Mean
observed
residue
values
from
DAT
0
through
DAT
0.5
were
used
for
the
DAT
0
short
term
assessments.
Mean
observed
residue
values
from
DAT
2
were
used
for
the
DAT
2
short
term
assessments.
c
Dermal
Dose
=
TTR
(µg/
cm
2
)
x
TC
(cm
2
/hr)
x
conversion
factor
(1
mg/
1,000
µg)
x
exposure
time
(2
hrs/
day
playing
&
mowing;
4
hrs
golfing)
x
Dermal
Absorption
Factor
(100%/
100)/
body
weight
(70
kg
adult
or
15
kg
child
1
6
yrs).
Short
term
MOEs
were
calculated
using
DAT
0
or
DAT
2
values.
d
MOE
=
NOAEL
(8.
46
mg/
kg/
day;
based
on
an
oral
study)
/
dermal
dose;
Note:
Target
MOE
is
300
or
greater;
numbers
are
rounded
to
two
significant
figures.
Note:
TTR
=
turf
transferable
residue
DAT
=
days
after
treatment
MOEs
in
bold
exceed
HEDs
level
of
concern
(i.
e.
MOEs
<
300).
33
Table
6.
Pronamide
Postapplication
Dermal
Cancer
Risk
Estimates
for
Activities
on
Treated
Turf
Activity
Typical
Application
Rate
(lb
ai/
acre)
(a)
Days
of
Exposure
per
Year
(b)
14
day
avg
TTR,
adjusted
for
"typical"
rate
(µg/
cm
2
)
(c)
Transfer
Coefficient
(cm2/
hr)
(d)
Absorbed
Dermal
Daily
Dose
(mg/
kg/
day)
(e)
LADD
(mg/
kg/
day)
(f)
Cancer
Risk
(g)
Days
of
Exposure
per
Year
to
Exceed
1.0E
06
High
contact
activities
1.0
1
0.07913
7300
1.65E
02
3.23E
05
8.36E
07
1.2
Mowing
1.0
1
0.07913
500
1.13E
03
2.21E
06
5.73E
08
17.5
Golfing
1.0
1
0.07913
500
2.26E
03
4.42E
06
1.15E
07
8.7
a
Typical
(not
maximum)
application
rates
were
used
to
adjust
TTR
study
residue
data;
rate
confirmed
per
label
and
registrants'
comments.
b
Average
or
typical
days
per
year
for
cancer
risk
estimates,
based
upon
a
single
annual
application
and
a
fairly
rapid
foliar
dissipation
rate
(half
life
of
1.8
days,
from
TTR
study,
i.
e.
MRID
#
44952501).
c
TTR
source:
MRID
#
44952501
turf
transferable
residue
study
see
Table
4
for
raw
data
and
regression
statistics.
Mean
observed
residue
values
for
DAT
0
through
DAT
14
were
used
for
the
assessment.
The
study
was
conducted
in
NC
using
a
maximum
application
rate
of
1.5
lb
ai/
acre.
When
assessing
activities
involving
a
different
application
rate
than
what
was
used
in
the
study,
the
TTR
values
are
adjusted
proportionately
to
reflect
the
different
application
rate.
For
example,
for
the
"typical"
application
rate
of
1.0
lb
ai/
acre
:
normalized
(adjusted)
TTR
=
Turf
study
TTR
x
1.0
lb
ai/
A
assessed
rate
/
1.5
lb
ai/
A
study
rate;
0.1187
µg/
cm
2
x
1.0
lb
ai/
A
assessed
rate
/
1.5
lb
ai/
A
study
rate
=
0.07913
µg/
cm
2
.
d
Transfer
coefficient
from
the
updated
Residential
SOP's
(02/
01).
e
Absorbed
daily
dose
=
Average
day
0
14
TTR
(µg/
cm
2
)
x
intermediate
term
transfer
coefficient
(cm
2
/hr)
x
mg/
1,000
µg
x
exposure
duration
(2
hrs/
day
for
playing/
gardening/
mowing;
4
hrs/
day
to
play
golf)
x
dermal
absorption
factor
(100%)
/
body
weight
(70
kg
adult).
f
LADD
=
absorbed
daily
dose
(mg/
kg/
day)
x
days
of
exposure/
year
x
50
years
of
expected
exposure/
(365
days/
year
x
70
year
lifetime);
g
Cancer
Risk
=
LADD
x
Q
1
*
,
where
Q
1
*
=
2.59
x
10
2
(mg/
kg/
day)
1
TTR
used
for
cancer
risk
estimate
=
0
14
DAT
average
residue
normalized
for
typical
application
rate.
TTR
=
turf
transferable
residue
DAT
=
days
after
treatment
34
Table
7.
Residential
Oral
Nondietary
Short
Term
Postapplication
Risks
to
Children
from
"Hand
to
Mouth"
and
Ingestion
Exposure
When
Reentering
Treated
Lawns
Type
of
Exposure
Short
term
Oral
Dose
a
(mg/
kg/
day)
Short
term
MOE
b
(1)
Hand
to
Mouth
Activity
(Finger
licking)
0.0224
380
(2)
Incidental
Object
to
Mouth
(Turfgrass
Mouthing)
0.0056
1500
(3)
Incidental
Ingestion
of
Soil
7.51E
5
113,000
Combined
Oral
Nondietary
c
0.028
300
Combined
Oral
and
Dermal
d
37
a
Application
rate
for
the
short
term
estimates
represents
maximum
label
rate
from
current
EPA
registered
label:
EPA
Reg.
No.
8660
85
wettable
powder
product
formulation,
max
rate
is
1.5
lb
ai/
acre.
Incidental
oral
doses
were
calculated
using
formulas
presented
in
the
Residential
SOPs
(updated
1999
2000).
Short
term
doses
were
calculated
using
the
following
formulas:
(1)
Hand
to
mouth
oral
dose
to
children
on
the
day
of
treatment
(mg/
kg/
day)
=
[application
rate
(lb
ai/
acre)
x
fraction
of
residue
dislodgeable
from
potentially
wet
hands
(5%)
x
11.2
(conversion
factor
to
convert
lb
ai/
acre
to
µg/
cm
2
)]
x
median
surface
area
for
1
3
fingers
(20
cm
2
/event)
x
hand
to
mouth
rate
(20
events/
hour)
x
exposure
time
(2
hr/
day)
x
0.001
mg/
:
g]
x
50%
extraction
by
saliva
/
bw
(15
kg
child
1
6
yrs).
This
formula
is
based
on
proposed
changes
to
the
December
1999
Residential
SOPs.
(2)
Turf
mouthing
oral
dose
to
child
on
the
day
of
treatment
(mg/
kg/
day)
=
[application
rate
(lb
ai/
acre)
x
fraction
of
residue
dislodgeable
for
transfer
to
mouth
(20%)
x
11.2
(conversion
factor
to
convert
lb
ai/
acre
to
µg/
cm
2
)
x
ingestion
rate
of
grass
(25
cm
2
/day)
x
0.001
mg/
:
g]
/
bw
(15
kg
child
1
6
yrs).
(3)
Soil
ingestion
oral
dose
to
child
on
the
day
of
treatment
(mg/
kg/
day)
=
[(
application
rate
(lb
ai/
acre)
x
fraction
of
residue
retained
on
uppermost
1
cm
of
soil
(100%
or
1.0/
cm)
x
4.54e+
08
µg/
lb
conversion
factor
x
2.47e
08
acre/
cm
2
conversion
factor
x
0.67
cm
3
/g
soil
conversion
factor)
x
100
mg/
day
ingestion
rate
x
1.0e
06
g/
µg
conversion
factor]
/
bw
(15
kg;
child
1
6
yrs).
Short
term
dose
based
residue
on
the
soil
on
day
of
application.
b
Short
term
MOE
=
NOAEL
(8.46
mg/
kg/
day)
/
Oral
Dose
(mg/
kg/
day).
NOAEL
from
a
non
developmental
toxicity
study
in
rabbits;
target
MOE
of
100.
Numbers
are
rounded
to
two
significant
figures.
c
Combined
MOEs
=
NOAEL
/
[sum
of
incidental
oral
doses],
with
a
target
MOE
of
100.
d
Combined
Dermal
+
Incidental
Oral
MOEs
=
1/
[1/
MOEdermal
+
1/
MOEoral
];
see
Table
5
for
dermal
MOE
for
high
contact
short
term
activity
for
toddlers
on
turf
(MOE
=
42).
MOEs
in
bold
exceed
HEDs
level
of
concern
(i.
e.
MOEs
<
300).
| epa | 2024-06-07T20:31:42.709582 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0159-0006/content.txt"
} |
EPA-HQ-OPP-2002-0159-0007 | Supporting & Related Material | "2002-07-12T04:00:00" | null | TXR
NO.
0050361
December
19,
2001
MEMORANDUM
SUBJECT:
PRONAMIDE
Report
of
the
FQPA
Safety
Factor
Committee
FROM:
Carol
Christensen,
Acting
Executive
Secretary
FQPA
Safety
Factor
Committee
Health
Effects
Division
(7509C)
THROUGH:
Ed
Zager,
Chair
FQPA
Safety
Factor
Committee
Health
Effects
Division
(7509C)
TO:
Jose
Morales,
Risk
Assessor
Reregistration
Branch
III
Health
Effects
Division
(7509C)
PC
Code:
101701
The
FQPA
Safety
Factor
Committee
evaluated
the
available
hazard
and
exposure
data
for
pronamide
on
December
3
rd
,
2001
and
made
the
recommendation
for
the
FQPA
safety
factor
to
be
used
in
human
health
risk
assessments
(as
required
by
Food
Quality
Protection
Act
of
August
3,
1996).
The
committee
concluded
that
the
FQPA
safety
factor
could
be
reduced
(3x)
in
assessing
the
risk
posed
by
this
chemical.
2
I.
HAZARD
ASSESSMENT
(Memorandum:
Michelle
Centra
to
Carol
Christensen,
dated
November
26,
2001)
A.
Adequacy
of
the
Toxicology
Database
The
toxicology
data
base
for
pronamide
is
adequate
for
FQPA
assessment.
The
toxicology
data
base
for
pronamide
was
reviewed
by
the
Hazard
Identification
Assessment
Review
Committee
(HIARC)
on
November
6
th
,
2001.
Prenatal
developmental
toxicity
studies
in
the
rabbit
and
a
two
generation
reproduction
study
are
available
with
pronamide.
However,
the
submitted
prenatal
developmental
toxicity
study
in
rats
was
evaluated
and
classified
as
unacceptable
guideline
(not
upgradeable).
Neither
a
LOAEL
nor
a
definitive
NOAEL
was
established
in
this
study,
and,
no
toxicities
were
observed
in
the
maternal
animals
and
their
fetuses.
B.
Determination
of
Susceptibility
The
results
of
the
available
developmental
toxicity
study
in
rabbits
and
two
generation
reproduction
study
in
rats
indicated
no
susceptibility
to
the
fetuses
of
rabbits
or
to
the
offspring
of
rats
following
pre
and/
or
postnatal
exposure
to
pronamide.
Fetal/
offspring
effects
in
both
the
rat
and
rabbit
were
observed
at
either
the
same
or
higher
dose
levels
which
produced
maternal/
parental
toxicity.
C.
Requirement
of
a
Developmental
Neurotoxicity
Study
The
HIARC
determined
that
a
developmental
neurotoxicity
study
in
rats
is
not
required.
However,
endocrine
effects
(thyroid,
testes,
ovaries,
adrenal
glands,
pituitary
gland,
thymus)
were
identified
in
the
majority
of
studies
conducted
across
species.
Since
thyroid
hormone
disruptions
are
known
to
be
associated
with
adverse
effects
on
neurological
development,
a
special
study
designed
to
assess
thyroid
function
in
adult
animals
and
their
offspring
will
be
required.
II.
EXPOSURE
ASSESSMENTS
A.
Dietary
Food
Exposure
Considerations
(Memorandum:
Jose
Morales
to
Carol
Christensen
on
November
27,
2001)
Pronamide
[3,5
dichloro
N(
1,1
dimethyl
2
propynyl)
benzamide]
is
a
selective,
systemic,
pre
and
post
emergence
herbicide
registered
for
the
control
of
grasses
and
broadleaf
weeds
in
several
food
and
feed
crops
as
well
as
woody
ornamentals,
Christmas
trees,
nursery
stocks,
lawns,
turfs,
and
fallow
land.
The
application
rates
range
from
0.2
lbs
ai/
A
to
4.0
lbs
ai/
A
and
can
be
applied
1
to
2
times
per
season.
There
are
no
Codex
MRLs
established
or
proposed
for
residues
of
pronamide
in
or
on
foods.
Tolerances
range
from
0.05
10
ppm.
Pronamide
is
a
systemic
herbicide.
The
qualitative
nature
of
the
residue
in
plants
and
3
animals
is
adequately
understood.
The
terminal
residues
of
concern
are
pronamide
and
its
metabolites
containing
the
3,5
dichlorobenzoyl
moiety.
Monitoring
data
are
available
from
the
Pesticide
Data
Program
(PDP)
for
the
years
1998
and
1999.
There
were
only
2
instances
of
detectable
residues.
Percent
of
crop
treated
data
are
also
available.
The
HED
Dietary
Exposure
Evaluation
Model
(DEEM)
will
be
used
to
assess
the
risk
from
dietary
exposure
to
pronamide
residues
in
food.
The
DEEM
analysis
will
be
refined
(Tier
II)
using
anticipated
residues
and
percent
of
crop
treated
data.
The
Committee
recognizes
that
further
refinement
to
the
dietary
food
exposure
analyses
may
be
required
as
the
risk
assessment
is
developed.
Therefore,
provided
the
final
dietary
food
exposure
assessment
includes
the
metabolites
of
toxicological
concern
does
not
underestimate
the
potential
risk
for
infants
and
children,
the
safety
factor
recommendations
of
this
Committee
stand.
B.
Dietary
Drinking
Water
Exposure
Considerations
(Correspondence:
Lucy
Shanaman
to
Carol
Christensen
on
November
27,
2001)
The
environmental
fate
data
base
for
the
parent
compound
(pronamide,
also
known
as
propyzamide)
is
complete.
Pronamide
is
relatively
mobile
and
persistent
in
the
environment,
and
therefore
could
possibly
move
to
surface
and
groundwater.
Only
the
parent
compound
pronamide
is
assessed
in
the
drinking
water
exposure
analysis.
Laboratory
studies
indicate
that
leaching
appears
to
be
the
major
route
of
dissipation
for
pronamide.
The
FIRST
and
SCI
GROW
models
will
be
used
to
estimate
environmental
concentrations
(EEC's)
of
pronamide
in
surface
water
and
groundwater.
These
models
are
considered
Tier
I.
The
ornamental
application
scenario
is
used
to
assess
water
exposure
because
application
rate
and
frequency
associated
with
this
use
is
expected
to
result
in
the
highest
modeled
EECs.
Monitoring
data
were
not
used
in
this
assessment
directly.
However,
available
data
do
indicate
that
the
values
estimated
through
modeling
are
conservative.
The
FQPA
Safety
Factor
Committee
recognizes
that
further
refinement
to
the
dietary
drinking
water
exposure
analyses
may
be
required
as
the
risk
assessment
is
developed.
Therefore,
provided
the
final
dietary
water
exposure
assessment
does
not
underestimate
the
potential
risk
for
infants
and
children,
the
safety
factor
recommendations
of
this
Committee
stand.
4
C.
Residential
Exposure
Considerations
(Correspondence:
Barry
O'Keefe
to
Carol
Christensen
on
November
27,
2001)
Use
of
pronamide
in
the
residential
environment
is
by
certified
applicators
only.
Postapplication
dermal
and
incidental
oral
exposures
to
children
and
infants
are
possible
from
exposure
to
lawns
and
turf
treated
with
pronamide.
Typical
application
rates
are
0.5
to
1.0
lbs
ai/
acre.
Applications
to
turf
are
only
made
in
the
late
Fall
or
late
Winter.
Therefore,
for
residential
turf,
it
is
reasonable
to
assume
that
typically
one
or
two
applications
are
made
per
year.
If
two
applications
were
made,
one
would
probably
be
made
in
late
Fall,
followed
by
another
application
in
late
Winter.
Both
a
registrant
submitted
turf
transferable
residue
(TTR)
study
and
the
EPA's
original
and
revised
Draft
SOPs
for
Residential
Exposure
Assessment
were
used
to
assess
postapplication
dermal
exposure
to
adults
and
children
as
well
as
incidental
oral
exposure
of
toddlers.
A
100%
dermal
absorption
factor
was
assumed.
Incident
data
are
available,
and
report
only
a
few
exposures.
5
II
SAFETY
FACTOR
RECOMMENDATION
AND
RATIONALE
A.
Recommendation
of
the
Factor
The
Committee
recommended
that
the
FQPA
safety
factor
be
reduced
to
3x.
B.
Rationale
for
Reducing
the
FQPA
Safety
Factor
The
FQPA
Committee
determined
that
the
safety
factor
is
necessary
when
assessing
the
risk
posed
by
pronamide
because:
1.
There
is
evidence
of
endocrine
effects
(thyroid,
testes,
ovaries,
adrenal
glands,
pituitary
gland,
thymus)
identified
in
the
majority
of
studies
conducted
across
species.
A
special
study
designed
to
assess
thyroid
function
in
adult
animals
and
their
offspring
will
be
required.
However,
the
Committee
concluded
that
the
safety
factor
could
be
reduced
for
pronamide
because:
1.
The
toxicological
database
is
adequate
for
FQPA
assessment;
and,
2.
There
is
no
indication
of
quantitative
or
qualitative
increased
susceptibility
of
rabbits
to
in
utero
exposure
or
to
rats
following
pre/
postnatal
exposure.
Also,
in
the
available,
unacceptable
rat
study,
no
increased
susceptibility
was
seen
even
though
the
animals
could
have
tolerated
higher
doses.
3.
A
developmental
neurotoxicity
study
is
not
required;
and,
4.
The
dietary
(food
and
drinking
water)
and
residential
exposure
assessments
will
not
underestimate
the
potential
exposures
for
infants
and
children.
C.
Application
of
the
Safety
Factor
Population
Subgroups/
Risk
Assessment
Scenarios:
All
population
subgroups:
The
3x
FQPA
Safety
factor
will
be
applied
when
assessing
chronic
dietary
and
short
term
residential
exposure
scenarios
because
of
evidence
of
endocrine
effects.
| epa | 2024-06-07T20:31:42.721982 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0159-0007/content.txt"
} |
EPA-HQ-OPP-2002-0159-0008 | Supporting & Related Material | "2002-07-12T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
August
10,
2001
MEMORANDUM
SUBJECT:
Review
of
Pronamide
Incident
Reports
DP
Barcode
D276937,
Chemical
#101701
FROM:
Jerome
Blondell,
Ph.
D.,
Health
Statistician
Chemistry
and
Exposure
Branch
1
Health
Effects
Division
(7509C)
Monica
F.
Spann,
M.
P.
H.,
Environmental
Health
Scientist
Chemistry
and
Exposure
Branch
1
Health
Effects
Division
(7509C)
THRU:
Francis
B.
Suhre,
Senior
Scientist
Chemistry
and
Exposure
Branch
1
Health
Effects
Division
(7509C)
TO:
Gary
Bangs,
Industrial
Hygienist
Reregistration
Branch
3
Health
Effects
Division
(7509C)
BACKGROUND
The
following
data
bases
have
been
consulted
for
the
poisoning
incident
data
on
the
active
ingredient
Pronamide
(PC
Code:
101701):
1)
OPP
Incident
Data
System
(IDS)
reports
of
incidents
from
various
sources,
including
registrants,
other
federal
and
state
health
and
environmental
agencies
and
individual
consumers,
submitted
to
OPP
since
1992.
Reports
submitted
to
the
Incident
Data
System
represent
anecdotal
reports
or
allegations
only,
unless
otherwise
stated.
Typically
no
conclusions
can
be
drawn
implicating
the
pesticide
as
a
cause
of
any
of
the
reported
health
effects.
Nevertheless,
sometimes
with
enough
cases
and/
or
enough
documentation
risk
mitigation
measures
may
be
suggested.
2
2)
Poison
Control
Centers
as
the
result
of
a
data
purchase
by
EPA,
OPP
received
Poison
Control
Center
data
covering
the
years
1993
through
1998
for
all
pesticides.
Most
of
the
national
Poison
Control
Centers
(PCCs)
participate
in
a
national
data
collection
system,
the
Toxic
Exposure
Surveillance
System
which
obtains
data
from
about
65
70
centers
at
hospitals
and
universities.
PCCs
provide
telephone
consultation
for
individuals
and
health
care
providers
on
suspected
poisonings,
involving
drugs,
household
products,
pesticides,
etc.
3)
California
Department
of
Pesticide
Regulation
California
has
collected
uniform
data
on
suspected
pesticide
poisonings
since
1982.
Physicians
are
required,
by
statute,
to
report
to
their
local
health
officer
all
occurrences
of
illness
suspected
of
being
related
to
exposure
to
pesticides.
The
majority
of
the
incidents
involve
workers.
Information
on
exposure
(worker
activity),
type
of
illness
(systemic,
eye,
skin,
eye/
skin
and
respiratory),
likelihood
of
a
causal
relationship,
and
number
of
days
off
work
and
in
the
hospital
are
provided.
4)
National
Pesticide
Telecommunications
Network
(NPTN)
NPTN
is
a
toll
free
information
service
supported
by
OPP.
A
ranking
of
the
top
200
active
ingredients
for
which
telephone
calls
were
received
during
calendar
years
1984
1991,
inclusive
has
been
prepared.
The
total
number
of
calls
was
tabulated
for
the
categories
human
incidents,
animal
incidents,
calls
for
information,
and
others.
PRONAMIDE
REVIEW
I.
Incident
Data
System
There
were
no
reported
cases
of
incidents
related
to
pronamide
in
the
Incident
Data
System
where
it
alone
was
responsible
for
an
incident.
II.
Poison
Control
Center
Data
1993
through
1998
Results
for
the
years
1993
through
1998
were
acquired
for
1
exposure
to
pronamide
reported
to
Poison
Control
Centers.
Cases
involving
exposures
to
multiple
products
are
excluded.
No
cases
were
reported
among
children
under
six
years
of
age
or
among
older
children
and
adults
exposed
at
their
workplace.
This
was
too
few
cases
to
warrant
detailed
analysis.
There
was
1
nonoccupationally
exposed
case
among
older
children
and
adults
which
was
not
reported
to
have
symptoms
related
to
their
exposure
and
was
not
seen
in
a
health
care
facility.
One
should
be
cautious
about
drawing
conclusions
from
such
a
small
number
of
cases
3
III.
California
Data
1982
through
1999
Detailed
descriptions
of
2
cases
submitted
to
the
California
Pesticide
Illness
Surveillance
Program
(1982
1999)
were
reviewed.
In
the
first
case,
a
worker
applied
the
product
on
the
ground
for
ten
days
and
reported
malaise,
anorexia,
fatigue,
dizziness,
nausea,
and
vomiting.
In
the
second
case,
one
of
two
workers
moved
an
irrigation
pipe
in
a
field
and
later
reported
dizziness,
vomiting,
and
weakness.
Both
cases
were
categorized
as
`possible',
meaning
the
exposure
was
a
possible
cause
of
the
reported
symptoms.
IV.
National
Pesticide
Telecommunications
Network
On
the
list
of
the
top
200
chemicals
for
which
NPTN
received
calls
from
1984
1991
inclusively,
pronamide
was
not
reported
to
be
involved
in
human
incidents.
VI.
Conclusions
Very
few
illness
cases
have
been
reported
due
to
pronamide
and
none
have
been
confirmed.
VII.
Recommendations
No
recommendations
can
be
made
on
the
very
limited
incident
data
available
for
this
pesticide.
cc:
Correspondence
Pronamide
file
(chemical
no.
101701)
Lori
Montford,
SRRD
(7508C)
| epa | 2024-06-07T20:31:42.724871 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0159-0008/content.txt"
} |
EPA-HQ-OPP-2002-0159-0009 | Supporting & Related Material | "2002-07-12T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION
PESTICIDES
AND
TOXIC
SUBSTANCES
TXR
NO.
0050364
MEMORANDUM
DATE:
December
10,
2001
SUBJECT:
Pronamide
(Propyzamide):
Report
of
the
Hazard
Identification
Assessment
Review
Committee
(HIARC)
Meeting
for
the
Herbicide,
Pronamide.
FROM:
Michelle
M.
Centra,
Pharmacologist
Reregistration
Branch
III
Health
Effects
Division
(7509C)
THRU:
Jess
Rowland,
Co
Chair
and
Elizabeth
Doyle,
Co
Chair
Hazard
Identification
Assessment
Review
Committee
Health
Effects
Division
(7509C)
TO:
Jose
Morales,
Chemist/
Risk
Assessor
Reregistration
Branch
III
Health
Effects
Division
(7509C)
PC
Code:
101701
On
November
6,
2001,
the
Health
Effects
Division
(HED)
Hazard
Identification
Assessment
Review
Committee
(HIARC)
reviewed
the
recommendations
of
the
toxicology
reviewer
for
PRONAMIDE
with
regard
to
the
acute
and
chronic
Reference
Doses
(RfDs)
and
the
toxicological
endpoint
selection
for
use
as
appropriate
in
occupational/
residential
exposure
risk
assessments.
The
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
PRONAMIDE
was
also
evaluated
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996.
The
conclusions
drawn
at
this
meeting
are
presented
in
this
report.
2
Committee
Members
in
Attendance
Members
present
were:
Jess
Rowland,
Elizabeth
Doyle,
William
Burnam,
Pamela
Hurley,
David
Nixon,
Paula
Deschamp,
Susan
Makris,
John
Liccione,
and
Brenda
Tarplee.
Member(
s)
in
absentia:
Ayaad
Assaad,
Jonathan
Chen,
and
Elizabeth
Mendez.
Data
evaluation
prepared
by:
Michelle
M.
Centra,
Reregistration
Branch
III.
Also
in
attendance
were:
Jose
Morales
(HED),
Barry
O'Keefe
(HED),
Steve
Knizner
(HED),
Virginia
Fornillo
(HED),
Lucy
Shanaman
(EFED),
Kevin
Crofton
(NHEERL/
ORD),
Michael
McDavit
(SRRD),
and
Cecelia
Watson
(SRRD).
Data
Evaluation
/
Report
Presentation
_______________________
Michelle
M.
Centra
Pharmacologist
3
Cl
Cl
O
C
CH
3
N
H
CH
CH
3
1.
INTRODUCTION
Pronamide
[3,5
dichloro
N(
1,1
dimethyl
2
propynyl)
benzamide],
trade
name
Kerb
®
,
is
a
selective,
systemic,
pre
and
post
emergence
herbicide
which
inhibits
root
and
shoot
growth
from
seedlings
and
is
used
to
control
a
wide
range
of
annual
and
perennial
grasses
as
well
as
certain
broadleaf
weeds.
Pronamide
is
produced
and
formulated
for
use
as
a
50
W
wettable
powder
in
water
soluble
pouches
(Kerb
®
,
EPA
Reg.
No.
707
159)
by
Rohm
and
Hass
Co.,
Springhouse,
Pennsylvania
and
may
be
applied
to
various
food/
feed
using
ground
spray
equipment,
by
soil
incorporation,
or
by
aircraft.
It
is
registered
for
use
in/
on
several
food
and
feed
crops
(alfalfa,
apples,
globe
artichokes,
birdsfoot
trefoil,
blackberries,
blueberries,
cherries,
clover,
crown
vetch,
endive,
grapes,
lettuce,
nectarines,
peaches,
pears,
plums,
prunes,
raspberries,
and
sainfoin).
Pronamide
is
also
registered
for
terrestrial
non
domestic,
non
food
use
on
woody
ornamentals
(azalea,
holly,
juniper,
pine,
rhododendron,
and
yew),
Christmas
trees,
nursery
stocks
(forsythia,
holly,
juniper,
pine,
rhododendron,
and
yew)
and
for
domestic
outdoor
uses
on
lawns,
turfs,
and
fallow
land
to
control
bermudagrass,
centipedegrass,
St.
Augustinegrass,
and
zoysiagrass.
Technical
pronamide
[also
known
as
propyzamide]
is
a
white
crystalline
solid
with
a
melting
point
of
155
156
0
C
and
a
specific
gravity
of
0.48
g/
cc.
Pronamide
is
soluble
in
water
(15
ppm
at
25
0
C);
in
dimethyl
sulfoxide
and
dimethyl
formamide
at
33
ppm;
in
mesityl
oxide,
isophorone,
methyl
ethyl
ketone,
and
cyclohexanone
at
20
ppm;
in
methanol,
isopropanol,
and
chlorobenzene
at
12
15
ppm;
in
butyl
cellosolve,
xylene,
acetonitrile,
and
kerosene
at
10
ppm;
and
in
nitrobenzene
and
ethylene
dichloride
at
5
ppm.
The
chemical
structure
of
pronamide
is
shown
below:
Empirical
Formula:
C12H11NOCl2
Molecular
Weight:
256.13
CAS
Registry
Number:
23950
58
5
On
November
6,
2001,
the
HIARC
met
to
evaluate
the
available
toxicology
data
base,
re
assess
the
existing
chronic
RfD,
select
the
toxicological
endpoints
for
occupational
and
residential
exposure
risk
assessments,
and
assess
the
potential
susceptibility
of
infants
and
children
from
exposure
as
required
by
the
FQPA
for
the
pronamide
tolerance
reassessment
eligibility
decision
(TRED).
4
2
HAZARD
IDENTIFICATION
2.1
Acute
Reference
Dose
(RfD)
No
appropriate
endpoint
was
available
to
quantitate
risk
to
the
general
population
from
a
single
dose
administration
of
pronamide.
The
developmental
effect,
abortions,
were
not
considered
to
occur
after
a
single
dose
in
this
instance
because
they
were
observed
in
rabbits
during
the
postdosing
phase
of
the
study
(days
22
24).
Therefore,
no
endpoint
was
chosen
to
quantitate
risk
to
females
13
50
from
a
single
dose
administration
of
pronamide.
2.2
Chronic
Reference
Dose
(RfD)
Study
Selected:
Chronic
Toxicity/
Carcinogenicity
in
Rats
Guideline
#:
870.4300
MRID
No.:
41714001,
41714002
Executive
Summary:
In
a
chronic
oral
(dietary)
toxicity/
carcinogenicity
study
(MRID#
41714001
and
41714002),
Crl:
CD(
BR)
VAF/
Plus
Rats
(Supplier:
Charles
River
Laboratories,
Inc.,
Kingston,
NY)
received
either
0,
25,
100,
or
400
ppm
for
the
first
2
weeks
then
0,
35,
140,
or
560
ppm
for
the
next
3
weeks
and
then
0,
40,
200,
or
1000
ppm
thereafter
(equal
to
0,
1.73,
8.46,
and
42.59
mg/
kg/
day
for
males
and
0,
2.13,
10.69,
and
55.09
mg/
kg/
day
for
females,
respectively)
Kerb
®
Technical
(Purity:
96.4%;
Batch
No.
2
5002)
in
the
diet.
Animals
were
observed
twice
daily
for
moribundity,
mortality
and
toxic
signs.
Body
weights
and
food
consumption
were
recorded
weekly
for
14
weeks
and
then
biweekly
thereafter,
food
efficiency
was
calculated
at
26
and
53
weeks.
Ophthalmological
examinations
were
conducted
on
all
animals
prior
to
study
initiation
and
in
the
control
and
high
dose
animals
at
sacrifice
at
6,
12,
and
24
months.
Blood
was
collected
from
10
animals/
sex/
dose
group
in
the
satellite
groups
at
6
and
12
months
and
from
10
animals/
sex/
dose
group
at
24
months
for
hematological
and
clinical
chemistry
studies.
Urine
was
collected
form
10
animals/
sex/
dose
group
at
5
months
and
due
to
the
small
amount
of
urine
collected,
it
was
repeated
at
6
months.
At
11
months
in
the
satellite
group
and
23
months
in
the
main
study,
urine
was
collected
from
10
animals/
sex/
dose
group
in
the
control
and
high
dose
groups
and
prior
to
sacrifice
at
24
months,
urine
was
collected
from
the
low
and
mid
dose
groups.
Animals
were
sacrificed
as
specified
at
6,
12,
and
24
months
and
received
a
complete
gross
examination,
organs
were
weighed
as
required
and
required
tissues
were
collected
and
fixed
for
histopathological
examination.
At
1000
ppm
(55.09
mg/
kg/
day),
mean
body
weights
and
body
weight
gains
were
decreased
in
female
rats.
Increased
incidences
of
non
neoplastic
lesions
were
observed
in
the
liver,
thyroid,
and
ovaries
of
high
dose
(1000
ppm)
rats.
In
the
liver,
centrilobular
hypertrophy
was
observed
in
males
and
females
at
12
months
(65%
in
males;
95%
in
females)
and
24
months
(20%
in
males;
48%
in
females).
Hypertrophy
was
accompanied
by
eosinophilic
cell
alteration
at
24months
(positive
trend
in
both
sexes;
pair
wise
comparison
in
high
dose/
controls
for
males
and
females).
The
histologic
liver
changes
were
accompanied
by
increases
in
relative
(to
body)
weight
in
the
high
dose
groups
of
both
sexes.
In
the
thyroid,
follicular
cell
hypertrophy
was
observed
(positive
trend
in
males
and
in
females)
at
12
months
but
not
at
24
months.
The
increased
incidence
observed
at
1000
ppm
was
only
significant
(pair
wise
comparison
in
high
dose/
controls)
in
females.
At
24
months,
follicular
cell
hyperplasia
was
observed
in
females
(positive
trend)
but
the
increased
incidence
observed
at
5
1000
ppm
was
not
statistically
significant.
In
the
ovaries,
sertoliform
tubular
hyperplasia
(positive
trend)
was
observed
in
females
at
24
months
and
the
increase
in
incidence
observed
at
1000
ppm
was
significant
by
pair
wise
comparison.
No
toxicologic
effects
were
observed
at
25
ppm
or
200
ppm
treated
male
and
female
rats.
The
Systemic
Toxicity
NOAEL
was
200
ppm
(8.46
mg/
kg/
day
for
males;
10.69
mg/
kg/
day
for
females)
and
the
Systemic
Toxicity
LOAEL
was
1000
ppm
(42.59
mg/
kg/
day
for
males;
55.09
mg/
kg/
day
for
females)
based
on
increased
relative
liver
weight
and
the
non
neoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries.
At
1000
ppm,
in
the
24
month
phase,
both
male
and
female
rats
had
increased
rates
of
thyroid
follicular
cell
adenomas,
and
male
rats
had
an
increased
incidence
of
benign
testicular
interstitial
cell
tumors.
Thyroid
tumors
were
not
observed
until
weeks
53
and
82
for
males
and
females,
respectively,
and
testicular
tumors
were
not
observed
until
week
67.
The
increase
in
thyroid
tumor
rate
was
statistically
significant
by
pair
wise
comparison
(p
<
0.01)
only
in
males,
but
there
was
a
positive
trend
(p
<
0.01)
for
both
sexes.
Both
high
dose
male
and
female
tumor
rates
(21%
and
10%,
respectively)
exceeded
the
historical
control
range
which
was
0
14.8%
(mean
5%)
for
males
and
0
9.5%
(mean
2%)
for
females
(Hazleton
Laboratories,
Vienna,
VA:
historical
control
data
for
SD
rats
obtained
from
13
studies
conducted
between
1985
and
1990).
There
were
no
significant
differences
in
thyroid
follicular
cell
carcinoma
rates
between
groups.
There
was
increasing
trends
and/
or
rates
in
combined
thyroid
follicular
cell
adenomas
and
carcinomas
(trend
p
<
0.01
in
males,
p
<
0.05
in
females;
pair
wise
comparison
of
high
dose
males/
controls,
p
<
0.05)
which
were
a
reflection
of
the
treatment
related
changes
in
thyroid
follicular
cell
adenoma
rates.
The
increase
in
testicular
interstitial
cell
benign
tumor
rate
was
statistically
significant
by
pair
wise
comparison
(p
<
0.05)
and
there
was
a
positive
trend
(p
<
0.01).
In
high
dose
males,
the
tumor
rate
(27%)
exceeded
the
historical
range
of
4.8
18.2%
with
a
mean
value
of
5.6%
(Hazleton
Laboratories,
Vienna,
VA:
historical
control
data
for
SD
rats
obtained
from
11
studies
conducted
between
1985
and
1990).
In
the
12
month
phase,
thyroid
follicular
cell
and
testicular
interstitial
cell
neoplasia
were
not
observed
in
any
group.
Benign
pituitary
adenomas
of
the
pars
distalis
were
observed
in
every
dose
group
during
both
the
12
and
24
month
phases,
but
the
tumor
rates
were
statistically
comparable
among
all
groups.
The
respective
tumor
rates
for
the
0,
40,
200,
and
1000
ppm
dose
groups
were
1/
19,
0/
19,
0/
20,
and
3/
20
in
males
and
0/
20,
2/
20,
1/
19,
and
3/
20
in
females
in
the
12
month
phase
and
31/
60,
33/
60,
35/
60,
and
34/
60
in
males
and
49/
60,
49/
60,
49/
60,
and
54/
60
in
females
in
the
24
month
phase.
Under
the
conditions
of
this
study,
the
dosing
was
considered
adequate
for
assessing
carcinogenic
potential
of
Pronamide,
based
on
body
weight
gain
depressions
(p
<
0.05)
of
$
10%
observed
at
1000
ppm
(weeks
0
26
in
males;
weeks
0
52
in
females),
increased
relative
liver
weight
in
both
sexes
and
the
non
neoplastic
histological
changes
in
the
liver,
thyroid
and
ovaries.
The
statistical
evaluation
of
mortality
indicates
no
significant
incremental
changes
with
increasing
doses
of
pronamide
in
either
male
or
female
rats.
CLASSIFICATION:
This
study
is
classified
as
Acceptable
Guideline
and
satisfies
the
guideline
requirements
(OPPTS
870.4300;
§
85
3)
for
a
chronic
oral
(dietary)
toxicity/
carcinogenicity
study
in
rodents.
6
Dose
and
Endpoint
for
Establishing
RfD:
A
NOAEL
of
8.46
mg/
kg/
day
based
on
based
on
increased
relative
liver
weight
and
the
non
neoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries
observed
at
the
LOAEL
of
42.59
mg/
kg/
day.
Uncertainty
Factor(
s):
Uncertainty
factor
of
100
was
applied
to
account
for
intraspecies
extrapolation
(10x)
and
interspecies
variability
(10x).
Comments
about
Study/
Endpoint/
Uncertainty
Factor(
s):
The
current
RfD
(0.08
mg/
kg/
day)
for
pronamide
is
based
on
the
NOAEL
of
8.46
mg/
kg/
day
established
in
the
two
year
chronic
toxicity/
carcinogenicity
study
in
rats
(MRID
41714001,
41714002)
and
an
uncertainty
factor
of
100
(10x
for
intraspecies
extrapolation
and
10x
for
interspecies
variation).
The
LOAEL
of
42.59
mg/
kg/
day
was
based
on
increased
relative
liver
weight
and
non
neoplastic
histologic
changes
in
the
liver,
thyroid,
and
ovaries.
Since
the
long
term
feeding/
carcinogenicity
study
in
rats
is
appropriate
for
the
route
and
duration
of
exposure
and
the
dose/
endpoint
established
in
this
study
is
the
most
protective
dose
(NOAEL
=
8.46
mg/
kg/
day)
for
the
target
effects
of
concern
(organ
toxicities
in
the
liver,
thyroid,
and
ovaries)
in
the
available
pronamide
toxicity
data
base,
it
will
remain
as
the
study
selected
for
the
chronic
RfD.
2.3
Occupational/
Residential
Exposure
2.3.1
Short
Term
(1
30
Days)
Incidental
Oral
Exposure
Study
Selected:
Developmental
Toxicity
in
Rabbits
Guideline
#:
870.3700
MRID
No.:
00148065,
00148064
Executive
Summary:
In
a
prenatal
developmental
toxicity
study
(MRID#
00148065,
00148064),
pregnant
six
month
old
New
Zealand
white
rabbits
received
Pronamide
as
an
aqueous
suspension
in
0.5%
methyl
cellulose
by
gavage
from
gestation
days
7
through
19,
inclusive,
at
dose
levels
of
0,
5,
20,
or
80
mg/
kg/
day.
Each
animal
was
examined
once
daily
for
signs
of
toxicity
and
mortality.
Body
weights
were
recorded
on
gestation
days
0,
4,
7,
11,
15,
20,
25,
and
29.
All
surviving
rabbits
were
weighed
and
sacrificed
on
gestation
day
29,
the
numbers
or
corpora
lutea,
implantation
sites,
live
and
dead
fetuses
and
embyronic
deaths
were
recorded,
in
addition
the
maternal
livers,
gall
bladders
and
kidneys
(with
ureters)
were
removed
and
process
for
microscopic
examination.
All
live
fetuses
were
weighed
and
examined
for
external
abnormalities.
The
fetuses
were
then
sacrificed,
internally
sexed
and
the
viscera
was
examined
for
anomalies.
The
brain
was
examined
by
mid
coronal
incision
and
the
heart
by
a
modified
Staples
technique.
The
fetuses
were
then
fixed
and
cleared
and
stained
in
Alizarin
red
S
for
skeletal
examinations.
Maternal
toxicity
was
noted
at
the
mid
dose
as
soiled
anal
area,
anorexia,
and
punctate
vacuolation
of
hepatocytes.
The
high
dose
group
was
also
associated
with
abortions,
late
resorptions,
and
1
death
as
well
as
additional
histopathology
in
the
liver
(hepatocellular
necrosis
eosinophilia,
swelling
of
hepatocytes,
pigmentation
of
Kupffer
cells,
etc).
The
Maternal
Toxicity
NOAEL
is
5
mg/
kg/
day
and
Chronic
RfD
=
8.46
mg/
kg/
day
(NOAEL)
=
0.08
mg/
kg/
day
100
(UF)
7
the
Maternal
Toxicity
LOAEL
is
20
mg/
kg/
day
based
on
clinical
signs
of
toxicity
and
liver
effects.
Developmental
Toxicity
was
seen
at
the
high
dose
as
abortions.
The
Developmental
Toxicity
NOAEL
is
20
mg/
kg/
day
and
the
Developmental
Toxicity
LOAEL
is
80
mg/
kg/
day
based
on
abortions.
CLASSIFICATION:
This
study
is
classified
as
Acceptable
Guideline
and
satisfies
the
guideline
requirements
for
a
prenatal
developmental
toxicity
study
in
rabbits
(OPPTS
870.3700;
OPP
§83
3b).
Dose
and
Endpoint
for
Risk
Assessment:
An
adjusted
dose
of
8.46
mg/
kg/
day
was
established
for
use
in
this
risk
assessment.
The
dose
selection
is
based
on
a
maternal
toxicity
NOAEL
of
5
mg/
kg/
day
and
clinical
signs
of
toxicity
(soiled
anal
area
and
anorexia)
and
liver
effects
(punctate
vacuolation
of
hepatocytes)
observed
at
the
LOAEL
of
20
mg/
kg/
day
in
the
developmental
toxicity
study
conducted
in
rabbits.
Comments
about
Study/
Endpoint:
Although
the
developmental
toxicity
study
in
rabbits
selected
for
short
term
incidental
exposure
is
of
the
appropriate
route
(oral)
and
duration
(13
days),
the
NOAEL
(5
mg/
kg/
day)
in
this
study
is
lower
than
the
NOAEL
(8.46
mg/
kg/
day)
established
in
the
chronic
toxicity/
carcinogenicity
study
in
the
rat.
The
apparent
disparity
between
these
NOAELs
is
driven
by
the
the
doses
of
pronamide
selected
for
testing
in
these
studies.
The
HIARC
concluded
that
using
a
more
realistic
NOAEL
of
8.46
mg/
kg/
day
rather
than
5
mg/
kg/
day
would
provide
a
sufficiently
protective
dose
for
risk
assessment.
The
NOAEL
of
3
mg/
kg/
day
established
in
the
special
thyroid
study
conducted
in
male
rats
was
also
considered.
However
this
dose
was
not
selected
because
the
wide
gap
between
the
NOAEL
(3
mg/
kg/
day)
and
the
LOAEL
(67
mg/
kg/
day)
in
this
study
resulted
in
the
3
mg/
kg/
day
dose
(NOAEL)
being
artificially
low.
In
addition,
the
LOAEL
of
67
mg/
kg/
day
is
comparable
to
the
LOAEL
(56
mg/
kg/
day)
established
in
the
chronic
toxicity
/carcinogenicity
study
conducted
in
rats.
2.3.2
Intermediate
Term
(1
6
Months)
Incidental
Oral
Exposure
Study
Selected:
Chronic
Toxicity/
Carcinogenicity
in
Rats
Guideline
#:
870.4300
MRID
No.:
41714001,
41714002
Executive
Summary:
See
Chronic
Reference
Dose
(RfD),
Section
2.2
Dose
and
Endpoint
for
Risk
Assessment:
A
NOAEL
of
8.46
mg/
kg/
day
based
on
based
on
increased
relative
liver
weight
and
the
non
neoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries
observed
at
the
LOAEL
of
42.59
mg/
kg/
day.
Comments
about
Study/
Endpoint:
The
NOAEL
of
12.3
mg/
kg/
day
established
in
the
90
day
subchronic
toxicity
study
in
rats
was
considered
for
risk
assessment.
However,
the
severity
of
the
toxicities
(increased
absolute
and
relative
liver
weights
and
hepatocellular
hypertrophy)
observed
in
this
study
were
determined
to
be
minimal.
Since
this
NOAEL
(12.3
mg/
kg/
day)
is
numerically
close
to
the
NOAEL
of
8.46
mg/
kg/
day
established
in
the
8
long
term
toxicity
study
conducted
in
rats
and
the
organ
toxicities
(liver,
thyroid,
and
ovaries)
observed
in
the
24
month
study
occurred
as
early
as
6
months
and
continued
to
study
termination,
the
HIARC
determined
that
the
chronic
feeding/
carcinogenicity
study
in
rats
is
an
appropriate
study
for
the
(1
6
months)
intermediate
term
exposure
duration.
Therefore,
the
selection
of
a
NOAEL
of
8.46
mg/
kg/
day
for
the
intermediate
term
incidental
oral
exposure
scenario
is
adequately
protective
of
the
population
of
concern
(infants
and
children).
2.3.3
Dermal
Absorption
Percentage
(%)
Dermal
Absorption:
100%
dermal
absorption
(default
value).
Comments
about
Dermal
Absorption:
A
dermal
absorption
study
submitted
to
the
Agency
was
classified
as
unacceptable
because
1)
the
actual
dose
applied
to
the
skin
was
not
determined
and
2)
there
were
discrepancies
in
recovery
for
the
50W
formulation
doses
(78%
and
122%
of
nominal
doses).
In
addition,
there
were
no
dermal
toxicity
studies
submitted
which
could
be
used
for
comparison
to
oral
toxicity
studies.
A
100%
dermal
absorption
default
value
was
determined
for
risk
assessment
purposes
due
to
the
limitations
of
the
available
pronamide
toxicity
data
base
(absence
of
dermal
toxicity
studies
as
well
as
an
unacceptable
dermal
absorption
study).
2.3.4
Short
Term
(1
30
Days)
Dermal
Exposure
Study
Selected:
Developmental
Toxicity
in
Rabbits
Guideline#:
870.3700
MRID
No.:
00148065,
00148064
Executive
Summary:
See
Short
Term
(1
30
days)
Incidental
Oral
Exposure,
Section
2.3.1
Dose
and
Endpoint
for
Risk
Assessment:
An
adjusted
dose
of
8.46
mg/
kg/
day
was
established
for
use
in
this
risk
assessment.
The
dose
selection
is
based
on
a
maternal
toxicity
NOAEL
of
5
mg/
kg/
day
and
clinical
signs
of
toxicity
(soiled
anal
area
and
anorexia)
and
liver
effects
(punctate
vacuolation
of
hepatocytes)
observed
at
the
LOAEL
of
20
mg/
kg/
day
in
the
developmental
toxicity
study
conducted
in
rabbits.
Comments
about
Study/
Endpoint:
See
Short
Term
(1
30
days)
Incidental
Oral
Exposure,
Section
2.3.1.
Since
there
were
no
dermal
toxicity
studies
submitted,
it
is
appropriate
to
select
an
endpoint
from
an
oral
study
of
the
appropriate
duration
of
exposure.
A
dermal
absorption
factor
of
100%
should
be
applied
for
this
risk
assessment.
2.3.5
Intermediate
Term
(1
6
Months)
Dermal
Exposure
Study
Selected:
Chronic
Toxicity/
Carcinogenicity
in
Rats
Guideline
#:
870.4300
MRID
No.:
41714001,
41714002
Executive
Summary:
See
Chronic
Reference
Dose
(RfD),
Section
2.2
9
Dose
and
Endpoint
for
Risk
Assessment:
A
NOAEL
of
8.46
mg/
kg/
day
based
on
based
on
increased
relative
liver
weight
and
the
non
neoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries
observed
at
the
LOAEL
of
42.59
mg/
kg/
day.
Comments
about
Study/
Endpoint:
See
Intermediate
Term
(1
6
months)
Incidental
Oral
Exposure,
Section
2.3.2.
Since
no
dermal
toxicity
studies
were
submitted,
it
is
appropriate
to
select
an
oral
endpoint
from
a
study
of
the
appropriate
duration
of
exposure.
A
dermal
absorption
factor
of
100%
should
be
applied
for
this
risk
assessment.
2.3.6
Long
Term
(>
6
Months)
Dermal
Exposure
Study
Selected:
Chronic
Toxicity/
Carcinogenicity
in
Rats
Guideline
#:
870.4300
MRID
No.:
41714001,
41714002
Executive
Summary:
See
Chronic
Reference
Dose
(RfD),
Section
2.2
Dose
and
Endpoint
for
Risk
Assessment:
A
NOAEL
of
8.46
mg/
kg/
day
based
on
based
on
increased
relative
liver
weight
and
the
non
neoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries
observed
at
the
LOAEL
of
42.59
mg/
kg/
day.
Comments
about
Study/
Endpoint:
Since
no
dermal
toxicity
studies
were
submitted,
the
selected
endpoint
is
from
an
oral
study
of
the
appropriate
duration
of
exposure.
A
dermal
absorption
factor
of
100%
should
be
applied
for
this
risk
assessment.
2.3.7
Short
Term
(1
30
Days)
Inhalation
Exposure
Study
Selected:
Developmental
Toxicity
in
Rabbits
Guideline
#:
870.3700
MRID
No.:
00148065,
00148064
Executive
Summary:
See
Short
Term
(1
30
days)
Incidental
Oral
Exposure,
Section
2.3.1
Dose
and
Endpoint
for
Risk
Assessment:
An
adjusted
dose
of
8.46
mg/
kg/
day
was
established
for
use
in
this
risk
assessment.
The
dose
selection
is
based
on
a
maternal
toxicity
NOAEL
of
5
mg/
kg/
day
and
clinical
signs
of
toxicity
(soiled
anal
area
and
anorexia)
and
liver
effects
(punctate
vacuolation
of
hepatocytes)
observed
at
the
LOAEL
of
20
mg/
kg/
day
in
the
developmental
toxicity
study
conducted
in
rabbits.
Comments
about
Study/
Endpoint:
See
Short
Term
(1
30
days)
Incidental
Oral
Exposure,
Section
2.3.1.
With
the
exception
of
an
acute
oral
inhalation
toxicity
study
conducted
with
the
50W
Kerb
formulation,
no
other
inhalation
toxicity
studies
were
submitted.
Therefore,
an
oral
end
point
was
selected
from
a
study
of
the
appropriate
duration
of
exposure.
An
inhalation
absorption
factor
of
100%
should
be
applied
for
this
risk
assessment.
10
2.3.8
Intermediate
Term
(1
6
Months)
Inhalation
Exposure
Study
Selected:
Chronic
Toxicity/
Carcinogenicity
in
Rats
Guideline
#:
870.4300
MRID
No.:
41714001,
41714002
Executive
Summary:
See
Chronic
Reference
Dose
(RfD),
Section
2.2
Dose
and
Endpoint
for
Risk
Assessment:
A
NOAEL
of
8.46
mg/
kg/
day
based
on
based
on
increased
relative
liver
weight
and
the
non
neoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries
observed
at
the
LOAEL
of
42.59
mg/
kg/
day.
Comments
about
Study/
Endpoint:
See
Intermediate
term
(1
6
months)
Incidental
Oral
Exposure,
Section
2.3.2.
With
the
exception
of
an
acute
oral
inhalation
toxicity
study
conducted
with
the
50W
Kerb
formulation,
no
other
inhalation
toxicity
studies
were
submitted.
Therefore,
an
oral
end
point
was
selected
from
a
oral
study
of
the
appropriate
duration
of
exposure.
An
inhalation
absorption
factor
of
100%
should
be
applied
for
this
risk
assessment.
2.3.9
Long
Term
(>
6
Months)
Inhalation
Exposure
Study
Selected:
Chronic
Toxicity/
Carcinogenicity
in
Rats
Guideline
#:
870.4300
MRID
No.:
41714001,
41714002
Executive
Summary:
See
Chronic
Reference
Dose
(RfD),
Section
2.2
Dose
and
Endpoint
for
Risk
Assessment:
A
NOAEL
of
8.46
mg/
kg/
day
based
on
based
on
increased
relative
liver
weight
and
the
non
neoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries
observed
at
the
LOAEL
of
42.59
mg/
kg/
day.
Comments
about
Study/
Endpoint:
With
the
exception
of
an
acute
oral
inhalation
toxicity
study
conducted
with
the
50W
Kerb
formulation,
no
other
inhalation
toxicity
studies
were
submitted.
Therefore,
an
oral
end
point
was
selected
from
a
oral
study
of
the
appropriate
duration
of
exposure.
An
inhalation
absorption
factor
of
100%
should
be
applied
for
this
risk
assessment.
2.3.10
Margins
of
Exposure
for
Occupational/
Residential
Risk
Assessments
A
MOE
of
100
is
required
for
short,
intermediate,
and
long
term
occupational
risk
assessments
for
both
dermal
and
inhalation
routes
of
exposure.
This
includes
10x
for
interspecies
extrapolation
and
10x
for
intraspecies
variation.
The
acceptable
MOEs
for
residential
exposure
will
be
determined
by
the
FQPA
SF
committee.
11
2.4
Recommendation
for
Aggregate
Exposure
Risk
Assessments
For
short
term
exposure,
incidental
oral,
dermal,
and
inhalation
routes
can
be
aggregated
because
of
the
use
of
oral
equivalents
and
a
common
endpoint
(clinical
signs
of
toxicity
and
liver
effects).
For
intermediate
term
and
long
term
exposure,
incidental
oral,
dermal
and
inhalation
routes
can
be
aggregated
because
of
oral
equivalents
and
a
common
endpoint
(increased
relative
liver
weight
and
non
neoplastic
histologic
changes
in
the
liver,
thyroid,
and
ovaries).
3
CLASSIFICATION
OF
CARCINOGENIC
POTENTIAL
3.1
Combined
Chronic
Toxicity/
Carcinogenicity
Study
in
Rats
MRID
No.:
00417140,
00417141
Executive
Summary:
See
Chronic
Reference
Dose
(RfD),
Section
2.2
Discussion
of
Tumor
Data:
Statistical
analysis
of
tumor
rates
was
based
on
the
Cochran
Armitage
Trend
Test
and
Fisher's
Exact
Test
for
pair
wise
comparison
of
controls
and
each
treated
group
since
there
was
no
significant
statistical
evidence
of
differential
mortality
with
increasing
doses
of
Pronamide.
At
1000
ppm,
in
the
24
month
phase,
both
male
and
female
rats
had
increased
rates
of
thyroid
follicular
cell
adenomas,
and
male
rats
had
an
increased
incidence
of
benign
testicular
interstitial
cell
tumors.
Thyroid
tumors
were
not
observed
until
weeks
53
and
82
for
males
and
females,
respectively,
and
testicular
tumors
were
not
observed
until
week
67.
The
increase
in
thyroid
tumor
rate
was
statistically
significant
by
pair
wise
comparison
(p
<
0.01)
only
in
males,
but
there
was
a
positive
trend
(p
<
0.01)
for
both
sexes.
Both
high
dose
male
and
female
tumor
rates
(21%
and
10%,
respectively)
exceeded
the
historical
control
range
which
was
0
14.8%
(mean
5%)
for
males
and
0
9.5%
(mean
2%)
for
females
(Hazleton
Laboratories,
Vienna,
VA:
historical
control
data
for
SD
rats
obtained
from
13
studies
conducted
between
1985
and
1990).
There
were
no
significant
differences
in
thyroid
follicular
cell
carcinoma
rates
between
groups.
There
were
increasing
trends
and/
or
rates
in
combined
thyroid
follicular
cell
adenomas
and
carcinomas
(trend
p
<
0.01
in
males,
p
<
0.05
in
females;
pair
wise
comparison
of
high
dose
males/
controls,
p
<
0.05)
which
were
a
reflection
of
the
treatment
related
changes
in
thyroid
follicular
cell
adenoma
rates.
The
increase
in
testicular
interstitial
cell
benign
tumor
rate
was
statistically
significant
by
pair
wise
comparison
(p
<
0.05)
and
there
was
a
positive
trend
(p
<
0.01).
In
high
dose
males,
the
tumor
rate
(27%)
exceeded
the
historical
range
of
4.8
18.2%
with
a
mean
value
of
5.6%
(Hazleton
Laboratories,
Vienna,
VA:
historical
control
data
for
SD
rats
obtained
from
11
studies
conducted
between
1985
and
1990).
In
the
12
month
phase,
thyroid
follicular
cell
and
testicular
interstitial
cell
neoplasia
were
not
observed
in
any
group.
Benign
pituitary
adenomas
of
the
pars
distalis
were
observed
in
every
dose
group
during
both
the
12
and
24
month
phases,
but
the
tumor
rates
were
statistically
comparable
among
all
groups.
The
respective
tumor
rates
for
the
0,
40,
200,
and
1000
ppm
dose
groups
were
1/
19,
0/
19,
0/
20,
and
3/
20
in
males
and
0/
20,
2/
20,
1/
19,
and
3/
20
in
females
in
the
12
month
phase
and
31/
60,
33/
60,
35/
60,
and
34/
60
in
males
and
49/
60,
49/
60,
49/
60,
and
54/
60
in
females
in
the
24
month
phase.
12
Adequacy
of
the
Dose
Levels
Tested:
The
dosing
was
considered
to
be
adequate
for
assessing
carcinogenic
potential
of
Pronamide,
based
on
body
weight
gain
depressions
(p
<
0.05)
of
$
10%
observed
at
1000
ppm
(weeks
0
26
in
males;
weeks
0
52
in
females).
Feed
consumption
was
also
depressed
(p
<
0.05)
at
1000
ppm
in
males
during
weeks
1
13
(7%),
1
26
(7%),
and
1
52
(5%).
Survival
rate
was
comparable
between
groups.
The
statistical
evaluation
of
mortality
indicates
no
significant
incremental
changes
with
increasing
doses
of
Pronamide
in
either
male
or
female
rats.
3.2
Carcinogenicity
Studies
in
Mice
Carcinogenicity
Study
in
Male
and
Female
Mice,
1974
MRID
No.:
00107968,
00066794
Executive
Summary:
In
a
carcinogenicity
study
(MRID#
00107968),
pronamide
(97
%
a.
i.)
was
administered
to
male
and
female
B6C3F1
mice
(125/
sex/
dose)
in
the
diet
at
dose
levels
of
0
(control)
1000,
or
2000
ppm
for
18
months.
This
corresponds
approximately
to
0,
150,
and
300
mg/
kg/
day.
Mice
(25/
sex/
dose)
were
sacrificed
at
the
end
of
a
30
week
treatment
period
(interim
sacrifice);
the
remaining
mice
were
sacrificed
at
the
end
of
the
18
month
treatment
period.
The
study
design
also
included,
for
comparison,
mice
treated
with
known
hepatocarcinogens,
including
4
6
mg/
kg/
day
diethylnitrosamine
(DEN)
and
2
acetamidofluorene
(AAF).
There
were
no
apparent
treatment
related
effects
on
survival.
At
the
end
of
the
18
month
study,
survival
rates
were
comparable
between
groups
with
no
gender
differences
(rates
greater
than
90%).
Significant
decreases
in
mean
body
weights
were
observed
in
females
treated
with
2000
ppm
(the
high
dose)
during
the
study.
Mean
body
weight
gains
were
reduced
in
the
low
dose
(1000
ppm)
females
(50
78
weeks),
the
high
dose
females
(0
30
weeks;
50
78
weeks)
and
the
high
dose
males
(
50
78
weeks).
At
interim
sacrifice,
absolute
and
relative
liver
weights
were
significantly
increased
in
the
low
dose
and
high
dose
females,
and
in
the
high
dose
males.
At
terminal
sacrifice,
relative
liver
weights
were
significantly
increased
in
the
low
and
high
dose
males
and
females.
A
dose
related
increase
in
the
incidence
of
hepatocellular
carcinomas
(respective
rates
at
0,
1000,
and
2000
ppm
were
7/
100,
18/
99,
and
24/
99)
was
observed
in
male
mice
sacrificed
at
18
months.
The
hepatocellular
carcinomas
were
characterized
as
non
metastisizing.
Pronamide
did
not
significantly
induce
hepatocellular
carcinomas
in
female
mice
compared
to
controls
(respective
rates
at
0,
1000,
and
2000
ppm
were
0/
100,
1/
100,
and
2/
100)
at
18
months.
Some
of
the
high
dose
males
exhibited
cholestasis
in
hepatocytes
and/
or
Kupffer's
cells.
The
LOAEL
is
1000
ppm
(150
mg/
kg/
day)
based
on
decreased
body
weight
gain
in
treated
females
and
increased
relative
(to
body
weight)
liver
weights
in
both
sexes.
A
NOAEL
was
not
established.
Under
the
conditions
of
this
study,
there
was
evidence
of
a
treatment
related
increase
in
tumor
incidence
in
the
livers
of
male
mice
when
compared
to
controls.
Dosing
is
considered
adequate
to
assess
the
carcinogenic
potential
of
pronamide
based
on
body
weight
gain
depressions
in
treated
females
and
increases
in
relative
(to
body)
weight
of
the
liver
at
$
1000
ppm
in
both
sexes.
Although
this
study
would
not
normally
meet
the
guideline
requirement
for
a
carcinogenicity
study
(83
2b)
in
this
species
(i.
e.,
study
deficiencies
included
lack
of
dietary
analyses
and
food
consumption
to
ensure
homogeneity,
stability,
and
concentration
of
test
material
in
the
diet,
and
to
13
assess
potential
palatability
problems
with
the
diet),
confidence
in
the
reported
tumor
data
is
enhanced
by
the
findings
of
a
subsequent
1982
special
carcinogenicity
study
in
male
mice
(MRID#
001114114)
that
confirm
the
tumor
findings.
Moreover,
if
reviewed
in
conjunction
with
the
1982
special
carcinogenicity
study
in
male
mice,
the
present
study
is
adequate
to
assess
the
carcinogenic
potential
of
pronamide
in
mice,
and
can
be
used
for
regulatory
and
risk
assessment
purposes.
Discussion
of
Tumor
Data:
A
dose
related
increase
in
the
incidence
of
hepatocellular
carcinomas
was
observed
in
male
mice
sacrificed
at
termination
(18
months).
The
increases
in
tumor
rates
observed
at
1000
and
2000
ppm
were
both
statistically
significant
by
pair
wise
comparison
with
controls
(p
<
0.01).
Pronamide
did
not
induce
hepatocellular
carcinomas
in
female
mice
(rates
at
termination
were
0/
100
in
controls;
1/
100
at
1000
ppm;
2/
100
at
2000
ppm).
Survival
rates
of
all
groups
were
comparable
(
$
90%).
Adequacy
of
the
Dose
Levels
Tested:
The
dosing
was
considered
to
be
adequate
for
assessing
the
carcinogenic
potential
of
Pronamide,
based
on
body
weight
gain
depressions
in
high
dose
females
(16.5%
decrease,
weeks
2
78,
p
<
0.05),
and
increasers
in
relative
body
weight
of
the
liver
at
$
1000
ppm
in
both
sexes
[23%
at
1000
ppm
and
41%
at
2000
ppm,
p
<
0.05
(males);
14%
at
1000
ppm
and
36%
at
2000
ppm,
p
<
0.05
(females)].
Carcinogenicity
Study
in
Male
Mice,
1982
MRID
No.:
00114114,
00151822
Executive
Summary:
In
a
special
carcinogenicity
study
(MRID#
0011411),
pronamide
(93.8
99%
a.
i.)
was
administered
to
male
B6C3F1
mice
(63/
group)
in
the
diet
at
dose
levels
of
0
(control
group1
and
control
group
2),
20,
100,
500,
or
2500
ppm
for
24
months.
This
corresponds
to
0,
3,
15,
75,
and
375
mg/
kg/
day.
The
two
matched
control
groups
received
untreated
diet.
Additional
groups
were
assigned
to
interim
sacrifices
at
6
months
(42
mice
at
0
ppm;
42
mice
at
2500
ppm)
and
at
15
and
18
months
(42/
group
including
control
groups
1
and
2,
and
20,
100,
500,
and
2500
ppm
groups).
Survival
rats
were
greater
than
93%
for
all
groups.
Both
the
500
ppm
and
2500
ppm
males
exhibited
gross
findings
of
increased
incidences
of
liver
nodules/
masses
and
enlarged
livers
at
the
24
month
interval.
Non
neoplastic
hepatic
effects
observed
in
males
treated
with
the
high
dose
(2500
ppm)
for
24
months,
included
increased
incidences
of
liver
enlargement,
liver
nodules/
masses,
hypertrophy,
parenchymal
necrosis,
and
cholestasis.
Administration
of
pronamide
also
resulted
in
decreased
body
weights.
The
results
of
the
special
study
confirmed
that
long
term
exposure
of
male
mice
to
pronamide
was
associated
with
an
increased
incidence
of
hepatocellular
carcinomas
(respective
rates
at
0,
0,
20,
100,
500,
or
2500
ppm
at
the
24
month
sacrifice
were
5/
63,
5/
63,
9/
63,
12/
63,
18/
63,
and
14/
61).
Additionally,
hepatocellular
adenomas
were
observed
(respective
rates
at
0,
0,
20,
100,
500,
or
2500
ppm
at
the
24
month
sacrifice
were
4/
63,
6/
63,
6/
63,
7/
63,
8/
63,
and
28/
61).
The
incidence
of
adenoma
and
carcinoma
was
significantly
increased
in
the
500
ppm
and
2500
ppm
males
when
compared
to
controls.
There
was
an
apparent
progression
from
benign
to
malignant
tumors.
This
special
study
confirmed
the
carcinogenic
effect
of
pronamide
in
male
mice.
The
LOAEL
is
500
ppm
(75
mg/
kg/
day)
based
on
gross
findings
(increased
incidences
of
hepatic
nodules/
masses
and
hepatic
enlargement)
observed
after
24
months
of
treatment.
The
NOAEL
is
100
ppm
(15
mg/
kg/
day).
14
Under
the
conditions
of
this
study,
there
was
evidence
of
a
treatment
related
increase
in
tumor
incidence
in
the
liver
of
male
mice
when
compared
to
controls.
Dosing
is
considered
adequate
to
assess
the
carcinogenic
potential
of
pronamide
based
on
liver
effects
(non
neoplastic
lesions
and
increased
weight).
This
special
carcinogenicity
study
in
the
male
mice
is
classified
as
Acceptable
Nonguideline.
The
data
confirmed
the
results
of
a
previously
conducted
carcinogenicity
study
in
mice
(1974,
MRID#
00107968).
When
reviewed
in
conjunction
with
the
1974
carcinogenicity
study,
these
two
studies
fulfill
the
guideline
requirement
for
a
carcinogenicity
study
[870.4200
(§
83
2b)]
in
mice
and
can
be
used
for
regulatory
and
risk
assessment
purposes.
Discussion
of
Tumor
Data:
This
study
confirmed
the
results
of
the
MCV
1974
study;
long
term
(24
months)
exposure
of
male
mice
to
Pronamide
was
associated
with
an
increased
incidence
of
hepatocellular
carcinomas.
A
positive
trend
(p
<
0.05)
in
incidences
of
hepatocellular
carcinomas
was
observed
in
mice
sacrificed
at
24
months,
and
the
increased
tumor
rates
observed
at
$
100
ppm
were
statistically
significant
(p
<
0.05
at
100
ppm;
p
<
0.01
at
500
and
2500
ppm).
Hepatocellular
adenomas
were
not
observed
in
pair
wise
differences
at
2500
ppm
(p
<
0.01)
in
mice
sacrificed
at
24
months
in
this
study.
There
also
appeared
to
be
a
progression
from
benign
to
malignant
tumors.
Survival
rates
were
excellent
for
all
groups
(
$
93%).
Adequacy
of
the
Dose
Levels
Tested:
The
dosing
was
considered
to
be
adequate
for
assessing
the
carcinogenic
potential
of
Pronamide,
based
on
decreased
body
weight
(30%,
months
6
24)
and
increased
liver
weight
(30
40%
absolute
weight
increase;
100%
relative
body
weight
increase)
in
the
high
dose
group.
3.3
Classification
of
Carcinogenic
Potential
In
accordance
with
the
Agency's
Proposed
Guideline
for
Carcinogen
Risk
Assessment
(April,
1996),
the
HED
Carcinogenicity
Peer
Review
Committee
(CPRC)
classified
Pronamide
as
a
Group
B2
chemical,
probable
human
carcinogen
with
inadequate
evidence
in
humans
(Memorandum:
N.
B.
Thoa
and
E.
Rinde,
May
26,
1993).
This
decision
was
based
on
the
finding
of
two
types
of
tumors
in
the
rat
(benign
testicular
interstitial
cell
tumors
and
uncommon
thyroid
follicular
cell
adenomas),
and
one
type
of
tumor
in
the
mouse
(hepatocellular
carcinomas).
A
linear,
low
dose
approach
(Q1*)
is
used
for
human
risk
characterization.
The
most
potent
unit
risk
Q1*,
based
on
male
mouse
liver
adenoma
and/
or
carcinoma
combined
tumor
rates,
is
2.59
x
10
2
(mg/
kg/
day)
1
in
human
equivalents
[converted
from
animal
to
humans
by
use
of
the
(mg/
kg
body
weight)
3/
4
interspecies
scaling
factor]
(Memorandum:
L.
Brunsman,
October
26,
2001,
TXR#
0050181).
4
MUTAGENICITY
With
the
exception
of
one
gene
mutation
toxicology
study,
the
remaining
five
mutagenicity
studies
were
reviewed
and
found
to
be
acceptable
for
regulatory
purposes
(The
acceptable
studies
statisfy
the
1991
mutagencity
guideline
requirements).
The
results
from
these
studies
indicate
that
pronamide
was
not
mutagenic
in
Salmonella
typhimurium,
Escherichia
coli
or
in
cultured
Chinese
hamster
lung
cells
and
did
not
produce
a
genotoxic
response
in
Bacillus
subtiltis
or
in
cultured
primary
rat
hepatocytes.
There
was
also
no
evidence
of
clastogenicity
in
cultured
Chinese
hamster
ovary
cells
and
pronamide
administration
did
not
result
in
the
induction
of
micronucleated
polychromatic
erythrocytes
in
bone
marrow
of
mice.
Overall,
the
data
suggest
that
pronamide
is
negative
for
mutagenicity
in
vitro
and
in
vivo.
15
Gene
Mutation
in
Salmonella
typhimurium/
mammalian
microsome
mutagenicity
assay;
OPPTS
870.5100
[§
84
2].
In
a
microbial
reverse
gene
mutation
assay
(MRID
No.
40090601)
Salmonella
typhimurium
strains
TA1535,
TA1537,
TA1538,
TA98
and
TA100
were
exposed
to
four
doses
of
propyzamide
as
RH
315
(purity
not
specified)
ranging
from
1
500
:
g/
plate
in
both
the
presence
and
the
absence
of
S9
activation.
The
S9
fractions
were
derived
from
Aroclor
1254
induced
C57BL/
6
x
C3H/
Anf
male
and
female
mouse
livers
and
the
test
material
was
delivered
to
the
test
system
in
an
unspecified
solvent.
Cytotoxicity
was
reported
at
levels
>500
µg/
plate
with
or
without
the
two
S9
fractions
(male
and
female
S9
fractions
were
processed
separately)
but
no
data
were
presented.
Strains
TA1535,
TA1538,
TA98
and
TA100
responded
in
the
expected
manner
to
the
solvent
and
the
appropriate
positive
controls.
However,
the
spontaneous
revertant
colony
counts
of
strain
TA1537
+/
S9
were
outside
of
the
expected
range
and
this
strain
failed
to
respond
to
the
positive
control,
activated
by
either
the
S9
fraction
derived
from
male
or
female
mouse
livers.
There
was
no
evidence
that
RH
315
induced
a
mutagenic
effect
in
any
strain
at
any
dose
without
or
without
the
S9
homogenates.
However,
the
study
is
not
valid
because
neither
the
test
material
purity
nor
the
solvent
were
reported,
the
claim
of
cytotoxicity
was
not
supported,
the
number
of
replicates
at
each
experimental
concentration
was
not
listed
and
strain
TA1537
performed
poorly.
This
study
is
classified
as
Unacceptable
and
does
not
satisfy
the
guideline
requirements
for
a
bacterial
gene
mutation
assay
(84
2).
Gene
Mutation
in
Salmonella
typhimurium
and
Escherichia
coli/
mammalian
microsome
mutagenicity
assay/
Bacillus
subtiltis
DNA
damage/
repair
assay;
OPPTS
870.5100/
5500
[§
84
2].
In
a
series
of
microbial
assays
(MRID
No.
40090602),
propyzamide
as
KERB®
(93.7%
a.
i.)
in
dimethyl
sulfoxide
(DMSO)
was
tested
for
the
ability
to
induce
reverse
gene
mutations
in
Salmonella
typhimurium
strains
TA1535,
TA1537,
TA1538,
TA98
and
TA100
and
in
Escherichia
coli
WP2
hcr
at
10
to
5000
:
g/
plate
in
both
the
presence
and
the
absence
of
S9
activation.
DNA
damage/
repair
was
assessed
in
Bacillus
subtilis
H17
(rec
+
)
and
M45
(rec
)
at
20
to
2000
:
g/
disc
with
and
without
S9
activation.
The
S9
fractions
were
derived
from
Aroclor
1254
induced
Sprague
Dawley
rat
livers.
No
cytotoxicity
was
seen
up
to
the
limit
dose
(5000
µg/
plate)
with
or
without
S9
activation
in
either
the
S.
typhimurium
or
the
E.
coli
strains
or
up
to
a
dose
approaching
the
limit
of
solubility
in
the
B.
subtilis
strains.
All
strains
responded
in
the
expected
manner
to
the
solvent
and
the
appropriate
positive
controls.
There
was
also
no
evidence
that
KERB®
induced
a
genotoxic
effect
in
any
strain
at
any
dose
without
or
without
the
S9
homogenate.
This
study
is
classified
as
Acceptable
and
satisfies
the
guideline
requirements
for
a
bacterial
gene
mutation
assay
and
a
bacterial
DNA
damage/
repair
assay
(84
2).
Gene
Mutation/
in
vitro
mammalian
cell
assay
in
Chinese
hamster
lung
(CHL)
cells;
OPPTS
870.5300
[§
84
2].
In
independently
performed
in
vitro
mammalian
cell
gene
mutation
assays
(MRID
No.
40211106),
cultures
of
Chinese
hamster
lung
(CHL)
fibroblasts
were
exposed
for
3
hours
to
concentrations
of
of
2.5
to
40
:
g/
mL
propyzamide
as
KERB®
Technical
(96.3%)
in
the
presence
and
absence
of
S9
activation.
Treated
cell
cultures
were
allowed
three
expression
times
(48,
96
and
168
hours)
with
or
without
S9
activation.
The
S9
homogenate
was
derived
from
rat
livers
induced
with
phenobarbitone
and
$
naphthoflavone
and
the
test
material
was
delivered
to
the
test
system
in
dimethyl
sulfoxide
(DMSO).
KERB®
Technical
was
slightly
cytotoxic
at
40
:
g/
mL+/
S9;
higher
levels
were
insoluble.
Cells
responded
as
expected
to
the
solvent
and
positive
controls.
There
was,
however,
no
evidence
that
KERB®
Technical
was
mutagenic
at
any
dose
under
any
assay
condition.
This
study
is
classified
as
Acceptable
and
satisfies
the
guideline
requirement
for
a
gene
mutation
in
cultured
mammalian
cell
assay
(§
84
2).
Cytogenetics/
in
vitro
mammalian
cell
assay
in
Chinese
hamster
ovary
(CHO)
cells;
OPPTS
870.5375
[§
84
2].
In
a
mammalian
cell
cytogenetic
assay
(MRID
No.
40211108),
cultured
Chinese
hamster
ovary
(CHO)
cells
were
exposed
continuously
to
propyzamide
as
KERB
technical
(94.2%)
at
seven
doses
ranging
from
16
25
400
:
g/
mL
in
the
absence
of
metabolic
activation
for
14
and
24
hours.
Cells
were
also
exposed
to
S9
activated
doses
of
25
400
:
g/
mL
for
2
hours
and
harvested
following
a
12
and
22
hour
recovery
period.
The
S9
homogenate
was
derived
from
Aroclor
1254
induced
Sprague
Dawley
rat
livers
and
the
test
material
was
delivered
to
the
test
system
in
dimethyl
sulfoxide.
Doses
$
250
:
g/
mL
were
insoluble;
cytotoxicity
was
not
seen
at
any
concentration.
The
positive
controls
induced
the
expected
clastogenic
responses
with
or
without
S9
activation.
There
was,
however,
no
evidence
that
KERB
technical
induced
a
clastogenic
response
either
in
the
presence
or
the
absence
of
S9
activation.
This
study
is
classified
as
Acceptable
and
satisfies
the
guideline
requirement
for
an
in
vitro
mammalian
cell
cytogenetic
assay
(§
84
2).
Cytogenetics/
in
vivo
mammalian
bone
marrow
chromosomal
aberration
test
in
mice;
OPPTS
870.5385
[§
84
2].
In
an
in
vivo
cytogenetic
assay
(MRID
No.
40211105),
groups
of
10
male
B6C3F1
mice
received
single
doses
of
480,
1940
or
4940
mg/
kg
propyzamide
as
KERB®
technical
(96.8%)
once
daily
for
1
day
or
for
5
consecutive
days
and
were
sacrificed
6,
12
or
24
hours
postdosing
(acute
exposure)
or
6
hours
postdosing
(subacute
exposure).
The
highest
assayed
dose
was
determined
based
on
the
estimated
oral
LD50
>5
g/
kg
in
male
B6C3F1
mice.
The
test
material
was
delivered
to
the
animals
in
0.5%
methyl
cellulose.
At
the
appropriate
sacrifice
intervals
(6,
24
and
48
hrs
postdosing
with
4940
mg/
kg
acute
exposure
or
6
hrs
after
the
5
day
administration
of
1940
mg/
kg/
day),
bone
marrow
cells
were
harvested
and
were
examined
for
the
incidence
of
structural
chromosome
aberrations.
Unscheduled
deaths
occurred
as
follows:
7%
in
the
acute
high
dose
group,
10%
in
the
subacute
intermediate
dose
group
and
60%
in
the
subacute
high
dose
group
(Days
2
or
3).
Other
signs
of
compound
toxicity
observed
in
the
surviving
animals
included
signs
of
central
nervous
system
depression
[i.
e.,
lethergy
and
ataxia
Day
1
(high
and
mid
dose
–acute
regimen);
lethergy,
ataxia,
reduced
spontaneous
motor
activity,
loss
of
righting
reflex,
catalepsy
and
abdominal
breathing
[Day
1
and/
or
Day
2
(high
and
mid
dose
–subacute
regimen)].
The
positive
control
induced
the
expected
significant
increase
in
the
frequency
of
cells
with
aberrant
chromosomes.
There
was,
however,
no
evidence
that
KERB®
technical
induced
a
clastogenic
effect
at
the
selected
dose
or
sacrifice
times.
The
study
is
classified
as
Acceptable
and
satisfies
the
requirements
for
FIFRA
Test
Guideline
84
2
for
in
vivo
cytogenetic
mutagenicity
data.
Other
Mutagenic
Mechanisms/
in
vitro
unscheduled
DNA
synthesis
in
mammalian
cells
in
culture;
OPPTS
870.5550
[§
84
2].
In
an
in
vitro
unscheduled
DNA
synthesis
(UDS)
assay
(MRID
No.
40211107),
primary
rat
hepatocytes
were
exposed
to
propyzamide
as
KERB®
technical
(94.2%)
at
9
doses
ranging
from
0.1
500
µg/
mL.
Hepatocytes,
harvested
19
hours
after
treatment
with
1,
5,
10,
25
or
50
µg/
mL
were
scored
for
net
nuclear
grains/
nucleus.
The
test
material
was
delivered
to
the
test
system
in
dimethyl
sulfoxide.
Cytotoxicity
(<
50%
cell
survival)
was
seen
at
$
100
µg/
mL
and
cells
treated
with
these
doses
were
not
scored.
The
positive
control
induced
the
expected
marked
increases
in
UDS.
There
was,
however,
no
evidence
that
KERB®
technical
induced
a
genotoxic
response.
This
study
is
classified
as
Acceptable
and
satisfies
the
guideline
requirement
for
a
UDS
assay
(84
2).
5
FQPA
CONSIDERATIONS
5.1
Adequacy
of
the
Data
Base
The
following
pronamide
toxicity
studies
are
available
and
adequate
for
evaluation
of
FQPA:
Developmental
Toxicity
Study
in
Rabbits
Two
Generation
Reproduction
Study
There
is
a
data
gap
for
a
developmental
toxicity
study
in
rats.
A
definitive
NOAEL
as
well
as
a
LOAEL
were
not
established
in
this
study;
no
toxicities
were
observed
in
the
maternal
animals
and
17
their
fetuses.
Therefore,
the
rat
developmental
toxicity
study
is
classified
as
unacceptable
guideline
(not
upgradeable)
and
can
not
be
used
for
endpoint
selection.
5.2
Neurotoxicity
Data
Mammalian
neurotoxicity
studies
for
Pronamide
have
not
been
conducted.
However,
since
this
chemical
is
not
an
organophosphate
and
there
is
no
evidence
of
neurotoxicity
seen
in
any
of
the
existing
studies,
neurotoxicity
studies
(e.
g.,
an
acute
delayed
neurotoxicity
study
in
the
hen,
a
neurotoxicity
screening
battery
or
a
developmental
neurotoxicity
study)
were
not
required.
5.3
Developmental
Toxicity
Developmental
Rat
In
a
prenatal
developmental
toxicity
study
(MRID#
40334501),
pregnant
Crl:
CD
®
BR
rats
(Charles
River
Breeding
Laboratories,
Montreal
Quebec)
received
KERB
®
Herbicide
(94.2%
a.
i.;
Lot
4859)
as
an
aqueous
suspension
in
0.5%
methyl
cellulose
by
gavage
from
gestation
days
6
through
15
inclusive
at
dose
levels
of
0,
5,
20,
80
or
160
mg/
kg/
day.
Each
animal
was
examined
once
daily
for
signs
of
toxicity
and
mortality.
Body
weights
were
recorded
on
gestation
days
0,
6,
8,
10,
13,
16,
and
20.
All
surviving
rats
were
sacrificed
on
gestation
day
20,
the
thoracic
and
abdominal
cavities
were
examined
for
gross
pathologic
changes.
The
gravid
uterus
was
weighed
and
the
the
numbers
of
corpora
lutea,
implantation
sites,
and
resorptions
were
recorded.
The
number
of
fetuses
were
counted
and
their
locations
in
the
uterus
were
recorded.
All
fetuses
were
weighed
and
examined
for
external
abnormalities.
Half
of
the
fetuses
were
then
fixed
and
cleared
and
stained
in
Alizarin
red
S
for
skeletal
examinations
and
the
other
half
were
examined
for
visceral
anomalies.
No
Maternal
Toxicity
was
noted
at
the
dose
levels
tested.
The
Maternal
Toxicity
NOAEL
is
equal
to
or
greater
than
160
mg/
kg/
day
and
the
Maternal
Toxicity
LOAEL
is
greater
than
160
mg/
kg/
day.
No
Developmental
Toxicity
was
noted
at
the
dose
levels
tested.
The
Developmental
Toxicity
NOAEL
is
equal
to
or
greater
than
160
mg/
kg/
day
and
the
Developmental
Toxicity
LOAEL
is
greater
than
160
mg/
kg/
day.
CLASSIFICATION:
This
study
is
classified
as
Unacceptable
Guideline
(not
upgradeable).
It
does
not
satisfy
the
guideline
requirements
for
a
prenatal
developmental
toxicity
study
in
rats
(OPPTS
870.3700;
OPP
§83
3a)
because
there
were
no
maternal
or
fetal
toxicities
observed
at
any
dose
tested
(a
LOAEL
was
not
established).
In
addition,
the
highest
dose
tested
may
not
be
the
definitive
NOAEL.
Developmental
Rabbit
See
Short
Term
Incidental
Oral
Exposure
(Section
2.3.1)
for
executive
summary.
18
5.4
Reproductive
Toxicity
Reproduction
Rat
In
a
2
generation
reproduction
study
(MRID#
41540301),
Pronamide
(93.1%
a.
i.;
Lot
Number
WHC1742
was
administered
to
Crl:
CD®
BR
Rats
(Charles
River
Labs,
Kingston,
N.
Y.)
in
the
diet
at
dose
levels
of
0,
40,
200
or
1500
ppm
(equal
to
3.1,
16.0
and
120.7
mg/
kg/
day
for
females
and
3.6,
18.0
and
130.1
mg/
kg/
day
for
males
for
the
40,
200
and
1500
ppm
dose
groups,
respectively)
through
2
generations
(one
mating
period
per
generation).
All
animals
were
observed
daily
for
clinical
signs
of
toxicity
and
twice
daily
for
mortality/
moribundity.
Individual
body
weights
and
food
consumption
were
recorded
weekly
during
the
premating
period
and
females
body
weights
were
recorded
on
gestation
days
0,
7,
14,
and
21
and
on
lactation
days
0,
7,
14,
and
21.
Reproductive
parameters
were
recorded
including
number
of
females
paired,
mated,
pregnant,
duration
of
gestation,
number
of
females
with
live
litters,
and
sex
ratio/
litter.
The
litter
observations
included
number
of
pups
born
alive
or
dead,
sex,
gross
abnormalities
and
the
pus
were
examined
twice
daily
for
mortality/
moribundity
and
were
weighed
and
examined
for
behavior
and
appearance
on
lactation
days
0,
4,
7,
14,
and
21.
All
animals
found
dead,
sacrificed
early
and
at
termination
were
subject
to
a
complete
necropsy,
this
included
all
pups
found
dead
before
weaning,
those
not
selected
for
breeding
and
all
F2
weanling
at
study
termination.
No
treatment
related
mortalities
and/
or
clinical
signs
were
observed
in
either
parental
(Pl
and
P2)
generations.
There
were
parental
systemic
effects
at
the
high
dose
based
on
decreases
in
body
weight
and
feed
consumption
in
both
sexes
and
increased
incidences
of
histopathology
of
the
liver
(centrilobular
hepatocytes
hypertrophy;
both
sexes),
adrenal
gland
(zona
glomerulosa
cellular
hypertrophy;
both
sexes),
thyroid
gland
(follicular
cell
hypertrophy;
females),
and
anterior
pituitary
gland
(cellular
hypertrophy;
males)
in
both
P1
and
P2
generations,
and
increased
incidences
of
uterine
gross
pathology
(black
foci/
serosal
surface)
in
P2
females.
The
Parental
Systemic
Toxicity
NOAEL
was
200
ppm
(16.0
mg/
kg/
day
for
females
and
18.0
mg/
kg/
day
for
males)
and
the
Parental
Systemic
LOAEL
was
1500
ppm
(120.7
mg/
kg/
day
for
females
and
130.1
mg/
kg/
day
for
males),
based
on
decreases
in
body
weight
and
feed
consumption
in
both
sexes
and
increased
incidences
of
histopathology
of
the
liver,
adrenal
gland,
thyroid
gland,
and
anterior
pituitary
gland
in
both
P1
and
P2
generations,
and
increased
incidences
of
uterine
gross
pathology
in
P2
females.
There
were
no
reproductive
effects
in
either
the
P1
or
P2
generations,
including
the
females'
mating,
fertility,
and
gestation
indexes,
the
number
of
pups
born
dead
or
alive/
litter
and
sex
ratio
per
litter.
The
Reproductive
Toxicity
NOAEL
is
equal
to
or
greater
than
1500
ppm
and
the
Reproductive
Toxicity
LOAEL
is
greater
than
1500
ppm.
There
were
no
effects
on
F1/
F2
litter
parameters
including
the
number
of
live
pups/
litter
on
lactation
days
0,
4,
7,
14,
or
21
and
the
viability
and
lactation
indexes.
Combined
(male
+
female)
F1/
F2
pups
body
weight/
litter
at
birth
and/
or
during
the
lactation
period
were
unaffected
by
the
low
or
mid
dose,
but
was
significantly
reduced
by
the
high
dose
(F1
at
birth
and
during
the
entire
lactation
period;
F2
during
lactation
days
14
and
21).
There
were
no
treatment
related
filial
abnormal
necropsy
findings.
The
Developmental/
Offspring
Toxicity
NOAEL
was
200
ppm
and
the
Developmental/
Offspring
Toxicity
LOAEL
was
1500
ppm,
based
on
decreases
in
combined
male/
female
pup
weight/
litter.
19
Classification:
This
study
is
classified
as
Acceptable
Guideline
and
satisfies
the
guideline
requirements
for
a
2
generation
reproductive
toxicity
study
in
rats
(OPPTS
870.3800;
OPP
§83
4).
5.5
Additional
Information
from
Literature
Sources
(if
available)
There
is
no
additional
toxicity
information
from
literature
sources
for
the
herbicide,
pronamide.
5.6
Determination
of
Susceptibility
There
was
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
in
the
fetuses
or
the
offspring
of
rats
or
rabbits
following
pre
and/
or
postnatal
exposure
to
pronamide.
In
the
prenatal
developmental
toxicity
study
in
rabbits
and
the
multigeneration
reproduction
study
in
rats,
any
observed
toxicity
to
the
fetuses
or
offspring
occurred
at
equivalent
or
higher
doses
than
did
toxicity
to
parental
animals.
Evidence
for
susceptibility
could
not
be
ascertained
in
the
developmental
toxicity
study
conducted
in
rats
because
there
were
no
maternal
or
fetal
toxicities
observed
at
any
dose
tested
(a
LOAEL
was
not
established).
In
addition,
the
highest
dose
tested
may
not
be
the
definitive
NOAEL.
The
HIARC
determined
that
this
study
is
a
data
gap.
Although
this
study
failed
to
demonstrate
maternal
and/
or
developmental
toxicities,
it
can
be
used
in
the
weight
of
evidence
evaluation
for
determining
the
FQPA
safety
factor
since
the
highest
dose
tested
in
this
rat
developmental
toxicity
study
exceeded
the
highest
doses
tested
in
both
the
rabbit
developmental
toxicity
study
(80
mg/
kg/
day)
and
the
rat
multigeneration
reproduction
study
(120.7
mg/
kg/
day
in
males;
130.1
mg/
kg/
day
in
females).
5.7
Determination
of
the
Need
for
Developmental
Neurotoxicity
Study
5.7.1
Evidence
that
suggest
requiring
a
Developmental
Neurotoxicity
study:
The
results
of
several
toxicity
studies
conducted
in
both
the
rat
and
dog
demonstrated
evidence
of
endocrine
organ
toxicity
(thyroid,
testes,
ovaries,
adrenal
glands,
pituitary
gland,
thymus)
following
exposure
to
pronamide.
Pronamide
is
listed
as
a
potential
endocrine
disruptor
on
EPA's
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(EDSTAC)
list.
5.7.2
Evidence
that
do
not
support
the
need
for
a
Developmental
Neurotoxicity
study
–
There
was
no
evidence
of
increased
susceptibility
to
rabbit
fetuses
in
the
developmental
toxicity
study
or
to
rat
offspring
in
the
multigeneration
reproduction
study
following
pronamide
exposure.
–
There
was
no
evidence
of
neurotoxicity
in
any
of
the
available
mammalian
toxicity
studies
conducted
with
pronamide.
The
HIARC
recommended
that
a
developmental
neurotoxicity
study
in
the
rat
not
be
required.
A
comparative
study
designed
to
assess
thyroid
function
in
adult
animals
and
their
offspring
as
well
as
potential
central
nervous
system
effects
in
the
young
will
be
required
due
to
endocrine
toxicities
20
observed
in
several
organ
systems
(thyroid,
testes,
ovaries,
adrenal
glands,
pituitary
gland
and
thymus)
of
the
rat
and/
or
dog.
Since
the
data
obtained
from
these
toxicity
studies
(a
special
endocrine/
thyroid
study
in
addition
to
the
required
guideline
studies)
are
suggestive
of
a
potential
hormonal
mechanism
for
thyroid
toxicity
and
considering
that
it
is
thyroid
hormone
which
is
essential
for
growth,
brain
development
and
nervous
system
maturation,
a
comparative
thyroid
assay
rather
than
a
developmental
neurotoxicity
study,
would
provide
a
more
complete
characterization
of
endocrine
disruption
(precursor
effects
in
the
thyroid)
associated
with
exposure
to
pronamide.
The
Registrant
is
advised
to
consult
the
Agency
with
regard
to
the
submission
of
a
thyroid
assay
protocol
prior
to
the
initiation
of
this
special
study.
6
HAZARD
CHARACTERIZATION
Pronamide
technical
has
a
low
order
of
acute
toxicity
via
the
oral,
dermal,
and
inhalation
routes
of
exposure
(Toxicity
Category
III
or
IV),
produces
mild
irritation
to
the
eyes
and
skin
(Toxicity
Category
IV),
and
is
not
a
dermal
sensitizer.
Pronamide
appears
to
be
a
liver
toxicant.
Adverse
liver
related
effects
(increases
in
liver
weight
and/
or
liver
related
serum
enzymes
and/
or
histopathology)
were
consistently
observed
in
every
animal
species
studied,
including
the
rat
(subchronic,
chronic,
and
2
generation
reproduction
studies),
mouse
(carcinogenicity
studies),
rabbit
(developmental
study),
and
dog
(subchronic
and
chronic
studies).
Other
target
organs
included
the
thyroid
in
rats
(increase
in
weight
and/
or
histopathology
observed
in
the
chronic
toxicity/
carcinogenicity
and
the
2
generation
reproduction
studies
as
well
as
a
subchronic,
special
13
week
thyroid
function
study),
the
testes
in
rats
(histopathology
in
the
chronic
toxicity/
carcinogenicity
study)
and
the
kidneys,
adrenal
glands
thymus,
heart,
testes,
and
brain
in
dogs
(increase
in
organ
weights
in
the
chronic
toxicity
study),
and
the
pituitary
in
rats
(histopathology
observed
in
the
subchronic
and
2
generation
reproduction
studies).
Many
chemicals
belonging
to
the
class
of
organochlorine
chemicals
are
known
to
produce
disruption
of
the
endocrine
system.
Pronamide
belongs
to
this
class
of
chemicals.
There
was
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
in
the
fetuses
or
the
offspring
of
rats
or
rabbits
following
pre
and/
or
postnatal
exposure
to
pronamide.
In
the
prenatal
developmental
toxicity
study
in
rabbits
and
the
multigeneration
reproduction
study
in
rats,
any
observed
toxicity
to
the
fetuses
or
offspring
occurred
at
equivalent
or
higher
doses
than
did
toxicity
to
parental
animals.
Although
the
highest
dose
of
pronamide
tested
in
the
rat
developmental
toxicity
study
exceeded
the
highest
doses
tested
in
both
the
rabbit
developmental
toxicity
study
and
the
rat
multigeneration
reproduction
study
without
demonstrating
toxicities,
it
failed
to
assess
the
potential
increased
susceptability
to
infants
and
children
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996.
The
Carcinogenicity
Peer
Review
Committee
(CPRC)
classified
Pronamide
as
a
group
B2
probable
human
carcinogen
with
inadequate
evidence
in
humans.
This
decision
was
based
on
the
finding
of
two
types
of
tumors
in
the
rat
(benign
testicular
interstitial
cell
tumors
and
uncommon
thyroid
follicular
cell
adenomas),
and
one
type
of
tumor
in
the
mouse
(hepatocellular
carcinomas).
A
linear,
low
dose
approach
(Q1*)
is
used
for
human
risk
characterization.
The
most
potent
unit
risk
Q1*,
based
on
male
mouse
liver
adenoma
and/
or
carcinoma
combined
tumor
rates,
is
2.59
x
10
2
(mg/
kg/
day)
1
in
human
equivalents
[converted
from
animal
to
humans
by
use
of
the
(mg/
kg
body
weight)
3/
4
interspecies
scaling
factor].
Although
endocrine
effects
have
been
observed
in
several
toxicity
studies,
the
data
provided
in
two
special
studies
conducted
to
explore
pronamide's
effect
on
hormonal
balance
in
support
of
a
threshold
mechanism
for
the
induction
of
thyroid
and
testicular
neoplasms,
are
incomplete.
Based
on
the
CPRC's
weight
of
the
evidence
evaluation
of
this
data
base,
it
was
determined
that
even
if
a
hormonal
mechanism
could
be
demonstrated
for
tumors
in
the
rat,
the
mouse
liver
tumors
can
not
be
discounted
(the
Q1*
is
based
on
the
21
incidence
of
liver
tumors
in
mice).
Therefore,
a
mechanistic
approach
to
risk
assessment
for
the
active
ingredient
pronamide
is
not
plausible.
Results
of
mutagenicity
studies
with
an
acceptable
classification
(forward
and
reverse
gene
mutation,
in
vivo
and
in
vitro
cytogenetic/
structural
chromosome
aberration
and
unscheduled
DNA
synthesis
assays)
indicate
that
pronamide
is
not
a
mutagenic
agent.
Mammalian
neurotoxicity
studies
for
Pronamide
have
not
been
conducted.
However,
since
this
chemical
is
not
an
organophosphate
and
there
is
no
evidence
of
neurotoxicity
seen
in
any
of
the
existing
studies,
neurotoxicity
studies
(e.
g.,
an
acute
delayed
neurotoxicity
study
in
the
hen,
a
neurotoxicity
screening
battery
or
a
developmental
neurotoxicity
study)
were
not
required.
Pronamide
is
rapidly
absorbed
and
completely
and
rapidly
eliminated;
the
radioactivity
administered
was
recovered
(93
103%)
in
the
urine
(40
61%),
feces
(40
60%)
and
tissues
and
carcass
(0.08
2.43%).
No
bioaccumulation
was
apparent
and
tissues
with
the
highest
radioactivity
content
were,
in
decreasing
order,
the
fat,
adrenals,
bone
marrow,
thyroids,
liver
kidney,
and
plasma.
The
elimination
of
radioactivity
from
the
plasma
of
low
dose
rats
was
biphasic
[rapid
phase
=
12.6
hrs
(males)
and
12.7
hrs
(females);
slow
phase
=
36.6
hrs
(males)
and
45.3
(females)]
and
that
of
the
high
dose
rats
was
monophasic
[t½
=
24.1
hrs
(males)
and
24.8
hrs
(females)].
Very
little
unchanged
pronamide
was
recovered
in
the
urine
and
no
significant
difference
in
urinary
metabolite
profile
was
observed
between
the
doses
or
the
sexes.
The
two
major
urinary
metabolites
were
SS47
70
(3.0
5.9%)
of
the
dose
and
metabolite
10
(12.7
18.9%).
In
the
urine,
27
metabolites
were
found
and
none
exceeded
3.3%
of
the
dose,
whereas,
almost
all
of
the
unknowns
were
less
than
1%
of
the
dose.
There
is
no
acceptable
dermal
absorption
study
in
the
pronamide
data
base.
In
addition,
there
were
no
dermal
toxicity
studies
submitted
which
could
be
used
for
comparison
to
oral
toxicity
studies.
Therefore,
a
100%
(default
value)
dermal
absorption
factor
was
determined
for
risk
assessment
purposes.
7
DATA
GAPS
Developmental
Toxicity
Study
in
Rats
21
Day
Dermal
Toxicity
Study
28
Day
Inhalation
Toxicity
Study
Dermal
Penetration
Study
A
Comparative
Thyroid
Rat
Assay
in
Adult
Animals
and
Offspring
22
8
ACUTE
TOXICITY
Acute
Toxicity
of
Pronamide
(Propyzamide)
Guideline
Number
Study
Type
MRID#
Results
Toxicity
Category
870.1100
(§
81
1)
Acute
Oral
Rat,
>
92.0%
a.
i.
00085505
LD50
(males
and
females)
>
5000
mg/
kg
IV
870.1100
(§
81
1)
Acute
Oral
(Limit
test)
Rat
95.7%
a.
i.
43583901
LD50
(males
and
females)
>
5000
mg/
kg
IV
870.1200
(§
81
2)
Acute
Dermal
(Limit
Test)
Rabbit,
95.7%
a.
i.
43583902
LD50
(males
and
females)
>
2000
mg/
kg
III
870.1300
(§
81
3)
Acute
Inhalation
Rat,
95.7%
a.
i.
44034201
LC50
>
2.1
mg/
L
(4
hour
exposure)
III
870.2400
(§
81
4)
Primary
Eye
Irritation
Rabbit
95.7%
a.
i.
43583904
Mild
occular
irritant
IV
870.2500
(§
81
5)
Primary
Dermal
Irritation
Rabbit,
95.7%
a.
i.
43583903
Slight
dermal
irritant
IV
870.2600
(§
81
6)
Dermal
Sensitization
Guinea
pig,
>
92.0%
a.
i.
00062605
Not
a
sensitizer
N/
A
23
9
SUMMARY
OF
TOXICOLOGY
ENDPOINT
SELECTION
The
doses
and
toxicological
endpoints
selected
for
various
exposure
scenarios
are
summarized
below
EXPOSURE
SCENARIO
DOSE
(MG/
KG/
DAY)
ENDPOINT
STUDY
Acute
Dietary
females
(13
50)
and
general
population
including
infants
and
children
No
appropriate
endpoint
was
available
to
quantitate
risk
to
the
general
population
from
a
single
dose
administration
of
pronamide.
The
developmental
effect,
abortions,
were
not
considered
to
occur
after
a
single
dose
in
this
instance
because
they
were
observed
in
rabbits
during
the
post
dosing
phase
of
the
study
(days
22
24).
Therefore,
no
endpoint
was
chosen
to
quantitate
risk
to
females
13
50
from
a
single
dose
administration
of
pronamide.
Chronic
Dietary
(all
populations)
NOAEL
=
8.46
Increased
relative
(to
body)
liver
weight
and
nonneoplastic
histologic
changes
in
the
liver,
thyroid,
and
ovaries.
Combined
Chronic
Toxicity/
Carcinogenicity
Study
Rat
UF
=
100
Chronic
RfD
=
0.08
mg/
kg/
day
Cancer
Q1*
=
2.59
x
10
2
(mg/
kg/
day)
1
Group
B2
chemical
"Probable
human
carcinogen"
based
on
thyroid
follicular
cell
adenomas
(males
and
females)
and
benign
interstitial
cell
tumors
(males)
in
rats
and
hepatocellular
carcinomas
in
male
mice.
Combined
Chronic
Toxicity/
Carcinogenicity
Study
Rat
Incidental
Oral,
Short
Term
NOAEL
=
8.46*
Clinical
signs
of
toxicity
(soiled
anal
area
and
anorexia)
and
liver
effects
(punctate
vacuolation
of
hepatocytes).
Developmental
Toxicity
Study
Rabbit
Incidental
Oral,
Intermediate
Term
NOAEL
=
8.46
Increased
relative
(to
body)
liver
weight
and
nonneoplastic
histologic
changes
in
the
liver,
thyroid,
and
ovaries.
Combined
Chronic
Toxicity/
Carcinogenicity
Study
Rat
Dermal,
Short
Term
a
NOAEL
=
8.46*
Clinical
signs
of
toxicity
(soiled
anal
area
and
anorexia)
and
liver
effects
(punctate
vacuolation
of
hepatocytes).
Developmental
Toxicity
Study
Rabbit
Dermal,
Intermediateand
long
Term
a
NOAEL
=
8.46
Increased
relative
(to
body)
liver
weight
and
nonneoplastic
histologic
changes
in
the
liver,
thyroid,
and
ovaries.
Combined
Chronic
Toxicity/
Carcinogenicity
Study
Rat
Inhalation,
Short
Term
a
NOAEL
=
8.46*
Clinical
signs
of
toxicity
(soiled
anal
area
and
anorexia)
and
liver
effects
(punctate
vacuolation
hepatocytes).
Developmental
Toxicity
Study
Rabbit
Inhalation,
Intermediateand
Long
Term
a
NOAEL
=
8.46
Increased
relative
(to
body)
liver
weight
and
nonneoplastic
histologic
changes
in
the
liver,
thyroid,
and
ovaries.
Combined
Chronic
Toxicity/
Carcinogenicity
Study
Rat
a
Since
an
oral
endpoint
was
selected,
a
dermal
absorption
factor
of
100%
(default
value)
and
an
inhalation
absorption
factor
of
100%
(default
value)
should
be
used
in
route
to
route
extrapolation.
*
An
adjusted
dose
of
8.46
mg/
kg/
day
was
established
for
use
in
this
risk
assessment
based
on
a
maternal
toxicity
NOAEL
of
5
mg/
kg/
day
and
clinical
signs
of
toxicity
(soiled
anal
area
and
anorexia)
and
liver
effects
(punctate
vacuolation
of
hepatocytes)
observed
at
the
LOAEL
of
20
mg/
kg/
day
in
the
developmental
toxicity
study
conducted
in
rabbits.
| epa | 2024-06-07T20:31:42.729533 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0159-0009/content.txt"
} |
EPA-HQ-OPP-2002-0159-0010 | Supporting & Related Material | "2002-07-12T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES,
ANDTOXIC
SUBSTANCES
March
8,
2002
MEMORANDUM
SUBJECT:
Pronamide.
Tolerance
Reassessment
Eligibility
Decision
(TRED).
Chemical
ID
No.
101701.
DP
Barcode
No.
D275194.
FROM:
Gary
Bangs,
Risk
Assessor
Michelle
Centra,
Pharmacologist
Jose
Morales,
Chemist
Barry
O'Keefe,
Biologist
David
Soderberg,
Chemist
Reregistration
Branch
3
Health
Effects
Division
(7509C)
THRU:
Catherine
Eiden,
Branch
Senior
Scientist
Reregistration
Branch
3
Health
Effects
Division
(7509C)
TO:
Cecelia
Watson,
Chemical
Review
Manager
Michael
McDavit,
Acting
Branch
Chief
Reregistration
Branch
II
Special
Review
and
Reregistration
Division
(7508W)
This
memorandum
and
attachments
constitute
the
Tolerance
Reassessment
Eligibility
Decision
(TRED)
for
pronamide
and
updates
the
Health
Effects
Division
(HED)
Chapter
of
the
Reregistration
Eligibility
Decision
Document
(RED)
for
pronamide
(August
24,
1993)
taking
into
consideration
requirements
of
the
1996
Food
Quality
Protection
Act
(FQPA).
The
Agency
RED
for
pronamide
was
issued
in
May
1994.
A
Tolerance
Reassessment
Eligibility
Decision
(TRED)
document
is
required
because
EPA
completed
the
RED
for
pronamide
before
passage
of
the
FQPA.
This
document
only
discusses
the
human
health
risk
assessment
required
for
reassessment
of
pesticide
residue
tolerances
and
does
not
revise
the
occupational
risk
assessment
conducted
in
the
1993
HED
human
health
risk
assessment
document.
Therefore,
data
submitted
for
assessment
of
occupational
exposure
have
been
used
only
for
non
dietary
(i.
e.,
residential)
risk
assessment
under
FQPA.
Cumulative
risk
assessment
considering
risks
from
other
pesticides
which
have
a
common
mechanism
of
toxicity
is
also
not
addressed
in
this
document.
NOTE:
Only
the
Rohm
and
Haas
94.6%
technical
and
51%
wettable
powder
formulation
are
subject
to
the
tolerance
reassessment.
Rohm
and
Haas
sold
this
product
to
Dow
Agro
Sciences
(Letter
sent
to
J.
Tompkins
in
RD,
9/
21/
01).
In
addition,
Earth
Care,
Division
of
United
Industries
Corp.,
(previously
Pursell
Industries)
has
requested
voluntary
cancellation
of
the
product
GREEN
UP
KERB
50W,
EPA
Reg.
No.
8660
85,
which
is
the
only
label
which
contains
a
residential
turf
use.
However,
as
of
the
time
of
this
TRED,
the
product
is
registered
and
a
postapplication
residential
exposure
and
risk
assessment
have
been
included
in
this
document.
Cancellation
of
the
GREEN
UP
label
(8660
85)
would
eliminate
all
uses
that
result
in
potential
public
or
residential
exposure.
Attachments:
C
Hazard
Identification
Assessment
Review
Committee
(HIARC)
report
(M.
Centra,
December
10,
2001)
C
Report
of
the
FQPA
Safety
Factor
Committee
(C.
Christensen,
December
19,
2001)
C
Toxicology
Chapter
of
the
Tolerance
Reassessment
Eligibility
Decision
(TRED)
(M.
Centra,
March
7,
2002)
C
Report
of
the
Mechanism
of
Toxicity
Assessment
Review
Committee
(MTARC)
(M.
Centra,
January
21,
2001)
C
Review
of
Pronamide
Incident
Reports
(
J.
Blondell
&
M..
Spann,
August
12,
2001)
C
Chronic
and
Cancer
Dietary
Exposure
Assessments
(D.
Soderberg,
et
al.,
February
7,
2002)
C
Pronamide
Residue
Chemistry
chapter
(J.
Morales,
February
28,
2002)
C
Residential
Risk
Assessment,
(B.
O'Keefe,
March
7,
2002)
C
Drinking
Water
Assessment
to
Support
TRED
for
Propyzamide
(Pronamide)
(L.
Shanaman,
May
16,
2001)
TABLE
OF
CONTENTS
1.0
EXECUTIVE
SUMMARY
.......................................................
1
2.0
PHYSICAL
CHEMICAL
PROPERTIES
CHARACTERIZATION
.....................
9
3.0
HAZARD
CHARACTERIZATION
................................................
9
3.1
Hazard
Profile
............................................................
9
3.2
FQPA
Considerations
.....................................................
19
3.3
Hazard
Endpoint
Selection
................................................
20
3.4
Endocrine
Disruption
.....................................................
24
4.
0
EXPOSURE
ASSESSMENT
..................................................
25
4.1
Summary
of
Registered
Uses
...............................................
25
4.2
Dietary
Exposure
and
Risk
Assessment
.......................................
26
4.2.1
Residues
in
Food
..................................................
26
4.3
Dietary
Exposure
from
Water
Sources
.......................................
29
4.3.1.
Environmental
Fate
..............................................
29
4.3.2
Drinking
Water
Exposure
Estimates
.................................
29
4.4
Residential
Exposure
......................................................
30
4.4.1
Residential/
Recreational
Postapplication
Exposure
and
Risk
............
30
4.4.2
Spray
Drift
.....................................................
35
5.0
AGGREGATE
RISK
ASSESSMENT
AND
RISK
CHARACTERIZATION
...........
35
5.1
Acute
Risk
...............................................................
36
5.2
Short
Term
Risk
.........................................................
36
5.2.1
Aggregate
Short
Term
Risk
Assessment
..............................
36
5.2.2
Short
Term
DWLOC
Calculations
.................................
36
5.3
Intermediate
Term
Risk
...................................................
37
5.4
Chronic
Risk
............................................................
37
5.5
Cancer
Risk
Estimates
.....................................................
39
5.5.1
Cancer
Aggregate
Risk
Assessment
.................................
39
5.5.2
Cancer
DWLOC
Calculations
.....................................
39
6.0
CUMULATIVE
EXPOSURE
TO
SUBSTANCES
WITH
A
COMMON
MECHANISM
OF
TOXICITY.................................................................
41
7.
0
INCIDENT
DATA...........................................................
42
8.0
TOLERANCE
REASSESSMENT
RECOMMENDATIONS
...........................
42
8.1
Tolerance
Reassessment
Recommendation
....................................
42
9.0
DATA
NEEDS
.................................................................
44
1
1.0
EXECUTIVE
SUMMARY
Purpose
A
Tolerance
Reassessment
Eligibility
Decision
(TRED)
document
is
required
for
pronamide
(propyzamide).
EPA
completed
the
1994
RED
for
pronamide
before
passage
of
the
1996
Food
Quality
Protection
Act
(FQPA).
Consequently,
pronamide
is
herein
reassessed
in
accordance
with
the
FQPA.
This
document
only
discusses
the
human
health
risk
assessment
required
for
reassessment
of
pesticide
residue
tolerances.
Potential
drinking
water
and
residential
exposure
is
also
considered
in
order
to
estimate
the
potential
aggregate
risk.
Cumulative
risk
assessment
considering
risks
from
other
pesticides
which
have
a
common
mechanism
of
toxicity
is
not
addressed
in
this
document.
Uses:
Pronamide
[3,5
dichloro
N(
1,1
dimethyl
2
propynyl)
benzamide]
is
a
selective,
systemic,
preand
post
emergence
herbicide
registered
for
the
control
of
grasses
and
broadleaf
weeds
in
several
food
and
feed
crops
as
well
as
woody
ornamentals,
Christmas
trees,
nursery
stocks,
turf,
and
fallow
land.
Pronamide
is
a
restricted
use
herbicide
applied
as
a
liquid
spray,
which
is
packaged
in
water
soluble
pouches
and
then
mixed
in
water
before
application.
It
is
a
soil
active
systemic
herbicide
with
uptake
by
susceptible
weeds
occurring
through
the
roots.
Application
rates
range
from
0.5
to
6
lbs
active
ingredient
(ai)
per
acre
per
application,
with
one
to
four
applications
per
year,
but
no
more
than
8
lbs
ai
per
acre
per
year.
Only
the
Rohm
and
Haas
94.6%
technical
and
51%
wettable
powder
formulation
are
subject
to
the
tolerance
reassessment.
Rohm
and
Haas
sold
this
product
to
Dow
Agro
Sciences
(Letter
sent
to
J.
Tompkins
in
RD,
9/
21/
01).
In
addition,
Earth
Care,
Division
of
United
Industries
Corp.,
(previously
Pursell
Industries)
has
requested
voluntary
cancellation
of
the
product
GREEN
UP
KERB
50W,
EPA
Reg.
No.
8660
85
(letter
to
C.
Watkins,
B.
Metzger,
1/
14/
02),
which
is
the
only
label
containing
a
residential/
recreational
turf
use.
Cancellation
of
the
GREEN
UP
label
(8660
85)
would
eliminate
all
uses
that
result
in
potential
public
or
residential
exposure.
Hazard
Assessment
Pronamide
technical
has
a
low
order
of
acute
toxicity
via
the
oral,
dermal,
and
inhalation
routes
of
exposure
(Toxicity
Category
III
or
IV),
produces
mild
irritation
to
the
eyes
and
skin
(Toxicity
Category
IV),
and
is
not
a
dermal
sensitizer.
The
active
ingredient
pronamide
appears
to
be
a
liver
toxicant.
Adverse
liver
related
effects
(increases
in
liver
weight
and/
or
liver
related
serum
enzymes
and/
or
histopathology)
were
consistently
observed
in
every
animal
species
studied,
including
the
rat
(subchronic,
chronic,
and
multi
generation
reproduction
studies),
mouse
(carcinogenicity
studies),
rabbit
(developmental
toxicity
study),
and
dog
(subchronic
and
chronic
studies).
Other
target
organs
included
the
thyroid
in
rats
(increase
in
weight
and/
or
histopathology
observed
in
the
chronic
toxicity/
carcinogenicity
and
the
multi
generation
reproduction
studies
as
well
as
a
subchronic,
special
13
week
thyroid
function
study),
the
testes
in
rats
(histopathology
in
the
chronic
toxicity/
carcinogenicity
study)
and
the
kidneys,
adrenal
glands,
thymus,
heart,
testes,
and
brain
in
dogs
(increase
in
organ
weights
in
the
chronic
toxicity
study),
and
the
pituitary
in
rats
(histopathology
observed
in
the
subchronic
and
multi
generation
reproduction
studies).
There
was
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
in
the
fetuses
or
the
2
offspring
of
rats
or
rabbits
following
pre
and/
or
postnatal
exposure
to
pronamide.
In
the
prenatal
developmental
toxicity
study
in
rabbits
and
the
multigeneration
reproduction
study
in
rats,
any
observed
toxicity
to
the
fetuses
or
offspring
occurred
at
equivalent
or
higher
doses
than
did
toxicity
to
parental
animals.
In
the
rat
developmental
toxicity
study,
the
highest
dose
of
pronamide
tested
exceeded
the
doses
tested
in
both
the
rabbit
developmental
toxicity
study
and
the
rat
multigeneration
reproduction
study
without
demonstrating
toxicities
in
either
maternal
animals
or
fetuses.
Since
this
study
failed
to
provide
evidence
concerning
the
potential
increased
susceptibility
to
infants
and
children
(a
LOAEL
was
not
be
established)
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996,
a
repeat
developmental
toxicity
study
in
the
rat
is
required
to
fulfill
the
OPPTS
harmonized
test
guideline
870.3700.
Results
of
the
battery
of
mutagenicity
studies
(forward
and
reverse
gene
mutation,
in
vivo
and
in
vitro
cytogenetic/
structural
chromosome
aberration
and
unscheduled
DNA
synthesis
assays)
indicate
that
pronamide
is
not
a
mutagenic
agent.
However,
the
Carcinogenicity
Peer
Review
Committee
(CPRC)
classified
Pronamide
as
a
group
B2
probable
human
carcinogen
(with
inadequate
evidence
in
humans)
based
on
the
finding
of
two
tumor
types
in
the
rat
(benign
testicular
interstitial
cell
tumors
and
uncommon
thyroid
follicular
cell
adenomas)
and
one
tumor
type
in
the
mouse
(hepatocellular
carcinomas).
A
linear,
low
dose
approach
(Q1*)
is
used
for
human
risk
characterization.
The
most
potent
unit
risk
Q1*,
based
on
male
mouse
liver
adenoma
and/
or
carcinoma
combined
tumor
rates,
is
2.59
x
10
2
(mg/
kg/
day)
1
in
human
equivalents
[converted
from
animals
to
humans
by
use
of
the
(mg/
kg
body
weight)
3/
4
interspecies
scaling
factor].
Pronamide
has
been
identified
by
the
Agency's
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(EDSTAC)
as
a
potential
endocrine
disruptor.
Evidence
of
endocrine
effects
from
several
guideline
toxicity
studies
as
well
as
two
special
studies
submitted
to
the
Agency
by
the
Registrant
include,
in
part,:
(i)
histopathology
of
the
thyroid
gland,
pituitary
gland,
adrenal
glands,
testes
and
ovaries,
(ii)
changes
in
hormone
levels;
decreased
T4
and
increased
TSH,
LH
and
FSH,
and
(iii)
the
induction
of
enzymes
such
as
cytochrome
P450
and
B5,
and
NADPH
cytochrome
c
reductase
in
addition
to
those
enzymes
involved
in
the
oxidation
of
testosterone.
Mammalian
neurotoxicity
studies
for
pronamide
have
not
been
conducted.
However,
since
pronamide
does
not
belong
to
a
class
of
chemicals
known
to
exhibit
neurotoxicity,
and
there
is
no
evidence
of
neurotoxicity
seen
in
any
of
the
existing
studies,
neurotoxicity
studies
(e.
g.,
an
acute
delayed
neurotoxicity
study
in
the
hen,
a
neurotoxicity
screening
battery
or
a
developmental
neurotoxicity
study)
are
not
required.
Pronamide
is
rapidly
absorbed
and
completely
and
rapidly
eliminated
equally
in
the
urine
(40
61%)
and
feces
(40
60%)
within
7
days
post
dosing.
No
bioaccumulation
was
apparent
and
very
little
unchanged
pronamide
was
recovered
in
the
urine.
All
of
the
fecal
metabolites
were
unidentified
and
comprised
less
than
1%
of
the
dose
whereas
two
major
urinary
metabolites
have
been
identified
and
quantified;
2(
3,5
dichlorophenyl)
4,4
dimethyl
5
carboxyoxazoline
(metabolite
SS47
70,
3.0
5.9%
of
the
administered
dose)
and
N
carboxymethyl
3,5
dichlorobenzamide
(metabolite
10,
12.7
18.9%
of
the
administered
dose).
There
is
no
acceptable
dermal
absorption
study
in
the
pronamide
data
base.
In
addition,
there
were
no
dermal
toxicity
studies
submitted
which
could
be
used
for
comparison
to
oral
toxicity
studies.
Therefore,
a
100%
(default
value)
dermal
absorption
factor
was
determined
for
risk
assessment
3
purposes.
A
FQPA
safety
factor
is
required
for
all
population
subgroups
when
assessing
dietary
and
residential
exposure
scenarios
because
of
the
evidence
of
endocrine
effects
in
the
pronamide
data
base.
However,
the
FQPA
safety
factor
was
reduced
to
3x
because:
(i)
the
toxicological
database
is
adequate
for
FQPA
assessment
(ii)
there
is
no
indication
of
quantitative
or
qualitative
increased
susceptibility
of
rabbits
to
in
utero
exposure
or
to
rats
following
pre/
post
natal
exposure.
Also,
in
the
available,
unacceptable
rat
study,
no
increased
susceptibility
was
seen
even
though
the
animals
could
have
tolerated
higher
doses
(iii)
a
developmental
neurotoxicity
study
is
not
required
and
(iv)
the
dietary
(food
and
drinking
water)
and
residential
exposure
assessments
will
not
underestimate
the
potential
exposures
for
infants
and
children.
Toxicological
endpoints
were
established
for
all
relevant
exposure
scenarios.
Acute
dietary
exposure
for
females
13
50
years
of
age
or
for
the
general
population
is
not
assessed
since
there
was
no
appropriate
endpoint
attributable
to
a
single
dose
available
in
the
pronamide
data
base.
Two
toxicological
studies
determined
all
toxicological
endpoint
doses
used
in
the
risk
assessment:
a
prenatal
developmental
toxicity
study
in
the
rabbit
and
a
chronic
toxicity/
carcinogenicity
in
the
rat.
A
discussion
of
the
dose
response
relationships
for
chronic
dietary
endpoints
as
well
as
residential
exposure
endpoints
follows
the
presentation
of
the
summary
of
toxicological
endpoint
selection
(See
Table
3,
Section
3.3
of
the
text).
A
chronic
reference
dose
(cRfD)
of
0.08
mg/
kg/
day
was
determined
on
the
basis
of
the
two
year
chronic
toxicity/
carcinogenicity
study
in
rats
and
the
application
of
an
uncertainty
factor
of
100
(10x
for
interspecies
extrapolation
and
10x
for
intra
species
variation).
The
NOAEL
in
this
study
was
8.46
mg/
kg/
day
and
the
LOAEL
was
42.59
mg/
kg/
day
based
upon
increased
relative
liver
weight
and
the
non
neoplastic
histologic
changes
in
the
liver
(centrilobular
hypertrophy
and
hepatocellular
eosinophilic
alteration
in
males
and
females),
thyroid
(follicular
cell
hypertrophy
in
males
and
females)
and
ovaries
(sertoliform
tubular
hyperplasia
in
females).
The
3x
FQPA
safety
factor
was
applied
to
the
chronic
dietary
risk
assessment
because
there
is
evidence
of
endocrine
effects
(thyroid,
testes,
ovaries,
adrenal
glands,
pituitary
gland,
thymus)
identified
in
the
majority
of
subchronic/
chronic
studies
conducted
across
species.
The
cPAD
is
the
cRfD
adjusted
for
the
FQPA
safety
factor.
Therefore,
the
cPAD
is
0.027
mg/
kg/
day.
Dietary
risk
estimates
which
are
less
than
100%
of
the
cPAD
do
not
exceed
HED's
level
of
concern.
For
risk
assessments
based
on
short
term
(1
30
days)
incidental
oral,
dermal
and
inhalation
exposures,
an
adjusted
dose
of
8.46
mg/
kg/
day
was
established
for
use
in
this
risk
assessment.
The
dose
selection
is
based
on
a
maternal
toxicity
NOAEL
of
5
mg/
kg/
day
and
the
clinical
signs
(soiled
anal
area
and
anorexia)
and
liver
effects
(punctate
vacuolation
of
hepatocytes)
observed
at
the
LOAEL
of
20
mg/
kg/
day
in
the
developmental
toxicity
study
conducted
in
rabbits.
Although
selection
of
this
study
for
short
term
exposure
scenarios
is
appropriate
for
the
route
(oral)
and
duration
(13
days),
the
NOAEL
of
5
mg/
kg/
day
is
lower
than
the
NOAEL
(8.46
mg/
kg/
day)
established
in
the
chronic
toxicity/
carcinogenicity
study
in
the
rat.
The
apparent
disparity
between
these
NOAELs
is
driven
by
the
doses
of
pronamide
selected
for
testing
in
these
studies.
The
Hazard
Identification
Assessment
Review
Committee
(HIARC)
concluded
that
using
a
more
realistic
NOAEL
of
8.46
mg/
kg/
day
rather
than
5
mg/
kg/
day
would
provide
a
sufficiently
protective
dose
for
risk
assessment.
The
3x
FQPA
safety
factor
was
also
applied
to
these
risk
assessments
because
of
the
evidence
of
endocrine
effects
in
the
pronamide
toxicity
data
base.
Due
to
the
lack
of
appropriate
dermal
or
inhalation
endpoints,
absorption
factors
of
4
100%
(default
value)
were
used
with
the
oral
endpoints.
Intermediate
and
long
term
toxicity
endpoints
were
also
selected,
however
only
short
term
oral,
dermal
or
inhalation
exposures
to
pronamide
are
anticipated,
based
on
its'
use
pattern.
Exposure
and
Risk
Assessment
There
is
a
potential
for
dietary
(food
and
drinking
water)
exposure
from
commercial
applications
of
pronamide
in
agriculture
and
for
postapplication
dermal
and
incidental
oral
exposures
from
residential/
recreational
uses
(lawns
and
turf).
If
the
label
allowing
residential/
recreational
turf
uses
is
canceled,
the
nondietary
exposures
will
be
eliminated.
The
occupational
exposure
was
assessed
in
the
1993
HED
RED
chapter.
However,
because
this
is
a
tolerance
reassessment
document,
only
nonoccupational
dietary
and
residential
postapplication
exposures
to
pronamide
are
considered
in
this
document.
Short
term,
chronic
and
cancer
exposures
were
assessed
for
pronamide
residues
in
food
and
water.
A
review
of
incident
data
sources
found
that
relatively
few
incidents
of
pronamide
poisonings
were
reported.
There
are
only
two
Poison
Center
reports,
no
incident
reports
in
OPP's
Incident
Data
System
and
only
two
reports
from
the
California
Pesticide
Illness
Surveillance
Program.
Dietary
The
dietary
risk
assessment
for
chronic
exposures
to
pronamide
shows
that
chronic
dietary
exposure
to
pronamide
is
not
a
significant
exposure
pathway.
As
stated
previously,
an
acute
toxicity
endpoint
was
not
selected,
therefore
an
acute
exposure
assessment
was
not
conducted.
Refined
tier
3
chronic
and
cancer
dietary
exposure
assessments
were
conducted
for
all
supported
food
uses
(i.
e.,
all
currently
registered
and
proposed
uses).
Pronamide
and
its
metabolites
containing
the
3,5
dichlorobenzoyl
moiety
are
the
residues
of
concern
and
are
included
in
the
assessment.
Although
tolerance
level
residues
were
used
for
four
registered
crops
(dried
peas,
endives,
radicchio,
and
cranberries),
the
assessment
was
based
primarily
upon
residue
monitoring
data
for
fruits
and
vegetables
and
upon
calculation
of
anticipated
residues
for
meat,
milk,
poultry
and
eggs,
and
is
the
most
refined
assessment
to
date
for
pronamide.
These
data
are
based
mostly
upon
non
detectable
residues.
Estimates
of
percent
crop
treated
(%
CT)
generated
by
the
Biological
and
Economic
Analysis
Division
(BEAD)
were
used
to
further
refine
the
dietary
exposure
assessment.
Estimates
were
generated
for
chronic
(long
term)
and
cancer
dietary
exposure
using
the
most
recent
version
of
the
Dietary
Exposure
Evaluation
Model
(DEEM™,
Version
7.75).
This
assessment
showed
that
the
chronic
dietary
risk
estimates
are
below
the
Agency's
level
of
concern
(<
100%
of
the
cPAD)
for
the
U.
S.
population
and
for
all
population
subgroups.
The
chronic
dietary
exposure
estimates
for
the
two
most
highly
exposed
population
subgroups,
children
(1
6)
and
seniors
(55+),
are
both
estimated
at
0.000005
mg/
kg/
day
(<
1%
cPAD).
The
cancer
dietary
risk
estimate
is
1.06
x
10
7
for
the
U.
S.
population,
and
is
below
the
level
that
the
Agency
generally
considers
to
be
of
concern
(1.0
x
10
6
or
one
in
one
million).
Residential
Postapplication
Exposure
Based
on
the
application
frequency
and
rate
of
residue
dissipation,
only
short
term
residential
5
postapplication
exposures
to
pronamide
are
anticipated
after
lawn
and
turf
treatments.
A
margin
of
exposure
(MOE)
of
300
(10x
for
interspecies
extrapolation,
10x
for
interspecies
variation
and
a
3x
FQPA
safety
factor)
is
required
for
short
term
incidental
oral,
dermal
and
inhalation
risk
assessments.
Therefore,
short
term
residential
risk
estimates
with
a
MOE
>
300
do
not
exceed
the
level
of
concern.
The
risk
assessment
for
short
term
residential
postapplication
exposure
indicates
that
dermal
exposures
to
pronamide
are
a
significant
pathway
of
exposure.
All
pronamide
end
use
products
are
labeled
as
restricted
use
pesticides.
Therefore,
consumers
are
restricted
from
handling
or
applying
pronamide
products.
Consequently,
only
residential/
recreational
postapplication
exposures
to
the
general
population
are
anticipated
and
are
evaluated
in
this
assessment.
Adults
and
children
are
potentially
exposed
to
pronamide
residues
via
the
dermal
route
after
application
of
pronamide
products
by
professional
lawn
care
operators
(LCOs)
in
residential/
recreational
settings.
Inhalation
exposure
to
pronamide
is
not
anticipated
after
application
due
to
the
low
vapor
pressure
of
the
active
ingredient
and
outdoor
air
dilution.
Incidental
oral
exposure
is
expected
to
occur
for
small
children
and
is
combined
with
their
dermal
exposures,
where
applicable
(i.
e.,
playing
on
turf).
Residential
exposures
were
estimated
based
on
label
application
frequency
and
the
persistence
of
pronamide.
Most
assumptions
for
risk
estimation
were
based
on
the
Agency's
Residential
SOPs.
Residents
are
assumed
to
play
or
work
on
treated
lawns
or
recreational
turf
within
the
first
24
hours
of
spraying.
Only
short
term
risks
from
residential
postapplication
dermal
and
incidental
oral
exposures
are
anticipated
since
turf
residues
dissipate
below
the
limit
of
quantitation
by
day
14
following
application
(based
on
the
submitted
pronamide
turf
transferable
residue
(TTR)
study).
Risk
estimates
based
on
residue
data
from
the
TTR
study
for
short
term
dermal
exposures
to
treated
turf
during
high
contact
lawn
activities
on
day
zero
following
application
(DAT
0)
exceed
HED's
level
of
concern,
i.
e.
result
in
MOEs
<
300
for
adults
(MOE
=
71)
and
children
(MOE
=
42).
After
the
turf
was
watered,
residues
declined
sufficiently
that
all
risk
estimates
were
below
the
level
of
concern
for
adults
(MOE
=
890)
and
children
(MOE
=
530).
However,
label
language
regarding
immediate
watering
in
after
application
to
turf
is
neither
required
nor
enforceable
for
consumers.
Risk
estimates
for
short
term
dermal
contact
with
residues
on
treated
turf
during
the
low
contact
activities
of
grass
mowing
or
golfing
on
the
day
of
treatment
do
not
exceed
the
level
of
concern
for
adults
(MOEs
2100
and
1000,
respectively).
Postapplication
cancer
risk
was
estimated
using
14
day
average
residues
and
only
a
single
day's
activity,
based
on
a
single
dormant
season
application.
The
estimated
cancer
risk
from
one
day
per
year
of
high
contact
(e.
g.,
playing
on
lawn)
postapplication
dermal
exposure
to
pronamide
treated
turf
was
8.4
x
10
7
and
did
not
exceed
the
Agency's
level
of
concern
of
1
x
10
6
.
Other,
lower
contact
activities
(e.
g.,
golfing)
could
be
conducted
for
several
days
without
exceeding
the
level
of
concern.
The
risk
estimates
for
small
children's
incidental
ingestion
of
pronamide
from
treated
turf
indicate
that
risks
do
not
exceed
the
level
of
concern
(i.
e.
MOEs
>
300)
for
hand
to
mouth
(MOE
=
380),
ingestion
of
soil
(MOE
=
113,000),
and
object
to
mouth
(MOE
=
1500)
scenarios.
The
small
children's
combined
oral
hand
to
mouth
incidental
ingestion
scenarios
(MOE
=
300)
also
do
not
exceed
the
level
of
concern.
When
risks
from
dermal
exposures
to
pronamide
by
small
children
are
combined
with
risks
from
incidental
oral
exposures,
the
combined
short
term
risk
estimates
exceed
the
level
of
concern
(MOEs
<
300),
with
a
MOE
of
37.
There
is
significant
uncertainty
involved
in
predicting
co
occurrence
of
exposures
by
different
routes
and
in
adding
these
scenarios,
as
well
as
the
degree
of
conservatism
generated
in
the
combined
risk
estimate.
6
Drinking
Water
Risk
assessment
for
short
term
and
chronic
exposure
to
pronamide
indicates
that
drinking
water
is
not
a
significant
exposure
pathway,
but
may
be
of
some
potential
concern
for
cancer.
Risk
estimates
for
exposure
to
pronamide
in
drinking
water
are
assessed
by
comparing
drinking
water
levels
of
comparison
(DWLOCs)
to
the
estimated
environmental
concentrations
(EECs)
of
pronamide
in
surface
water
and
groundwater.
In
the
case
of
pronamide,
there
are
monitoring
data
available
for
surface
and
ground
water.
The
monitoring
database
used
in
the
risk
assessment
is
considered
to
be
of
good
quality
(US
Geological
Survey),
but
the
data
are
not
specific
to
pronamide
use
areas.
Therefore
they
are
cited
for
comparison,
rather
than
verification
of
modeling
estimates.
A
Tier
I
Drinking
Water
Assessment
for
pronamide
was
calculated
(L.
Shanaman,
May
16,
2001)
using
the
SCIGROW
model
to
provide
groundwater
EECs.
The
Tier
I
groundwater
concentration
estimates
were
predicted
from
application
of
pronamide
at
maximum
label
rate,
and
represent
upper
bound
estimates
of
the
concentrations
that
might
be
found
in
shallow
groundwater
at
vulnerable
sites
due
to
the
use
of
pronamide/
propyzamine.
The
resulting
modeled
groundwater
screening
concentration
is
3.0
ppb,
which
does
not
exceed
the
DWLOC
for
short
term
exposure
for
the
most
sensitive
populations
(females
>55
years
)
of
560
ppb.
The
Tier
II
PRZM
EXAMS
model
(L.
Shanaman,
in
progress,
2002)
was
used
to
predict
EECs
for
pronamide
in
surface
water,
i.
e.,
90
th
percentile
average
annual
concentration
values
for
use
in
chronic
exposure
assessments,
and
36
year
mean
concentration
values
for
use
in
"cancer"
exposure
assessments.
Maximum
label
application
rates
were
used
for
major
use
crops.
Chronic
exposure
values
ranged
from
1.5
to
6.4
ppb,
which
are
lower
than
the
chronic
DWLOC
of
300
ppb
for
the
most
sensitive
populations,
infants
and
children.
Conservative
inputs
were
used
for
the
environmental
(soil
and
water
metabolism)
assumptions,
i.
e.,
2
3x
uncertainty
factors
were
applied
to
soil
and
water
half
lives
used
in
the
PRZMEXAMS
assessment.
The
Tier
II
cancer
risk
assessment
for
exposure
to
pronamide
in
water
indicates
that
drinking
water
may
be
a
significant
exposure
pathway.
The
the
refined
Tier
II
modeling
result
is
greater
than
the
aggregate
cancer
DWLOC
estimate
of
<0.1
ppb
and
therefore
exceeds
the
cancer
level
of
concern
of
1
x
10
6
.
The
estimated
DWLOC
for
cancer
based
on
dietary
exposures
only
(food
+
water)
is
1.2
ppb,
which
is
below
some
of
the
drinking
water
concentrations
estimated
by
EFED
and
above
others
(0.535
4.3
ppb
for
surface
water
and
3
ppb
for
groundwater)
and
therefore
is
of
concern
for
some
scenarios.
Surface
and
ground
water
monitoring
data
are
available
for
pronamide
from
routine
USGS
sampling,
and
are
being
analyzed
to
determine
if
they
provide
support
for
the
modeling
estimates.
Aggregate
Exposure
Aggregate
risk
assessments
were
conducted
for
short
term
and
chronic
exposures,
and
for
cancer.
All
of
the
aggregate
risk
estimates
are
considered
high
end,
or
conservative,
due
to
the
compounding
of
conservative
assumptions
in
individual
exposure
route
estimates.
Aggregate
risk
estimates
for
acute
exposures
were
not
conducted
as
no
acute
endpoint
was
selected
from
the
toxicity
database.
Because
there
are
no
intermediate
term
or
chronic
non
dietary
exposures
to
pronamide,
the
chronic
aggregate
risk
assessment
only
considers
exposures
from
dietary
(via
food
and
drinking
water)
consumption.
HED
has
no
concerns
for
aggregate
chronic
exposures
to
pronamide
residues
in
food
and
drinking
water.
7
Estimated
drinking
water
exposures
using
Tier
2
modeling
and
actual
sampling
data
for
surface
water
and
groundwater
result
in
equivocal
cancer
risk
estimates
of
approximately
1
to
3
x
10
6
,
independent
of
dietary
and
residential
exposures
to
pronamide.
Therefore,
HED
has
some
concerns
for
the
potential
exposures
from
surface
and
groundwater
sources
under
the
cancer
asessment,
particulary
for
the
scenario
assessed
surface
water
for
alfalfa
in
California.
Aggregated
exposures
from
food,
water,
and
residential
uses
result
in
cancer
risk
estimates
that
further
exceed
HED's
level
of
concern
for
cancer.
The
short
term
aggregate
risk
assessment
conducted
for
pronamide
considered
ingestion
of
food
and
drinking
water,
combined
with
postapplication
dermal
and
incidental
oral
exposures.
Because
the
risk
estimates
for
high
contact
dermal
exposures
for
both
children
and
adults
alone
are
of
concern,
a
shortterm
aggregate
exposure
assessment
was
not
conducted
for
those
populations
and
scenarios,
as
they
would
only
further
exceed
the
HED's
level
of
concern.
Risk
estimates
are
in
excess
of
the
level
of
concern
(MOE
<
300)
for
short
term
dermal
exposures
to
pronamide
residues
on
turf
for
adults
(MOE
=
71)
and
children
(MOE
=
42)
engaged
in
high
contact
activities,
such
as
playing
on
treated
turf
immediately
after
pronamide
application.
However,
as
the
risk
estimate
for
short
term
exposures
of
adults
golfing
does
not
exceed
HED's
level
of
concern,
HED
included
this
short
term
residential
exposure
with
food
and
drinking
water
exposure
in
a
short
term
aggregate
risk
assessment.
The
aggregate
risk
estimate
for
food
and
golfing
exposure
was
a
MOE
of
1050,
and
there
was
still
enough
room
to
add
the
estimated
drinking
water
exposure
without
exceeding
the
HED
DWLOC.
This
short
term
aggregate
risk
estimate
including
adults
engaged
in
lowcontact
activities
on
turf
may
be
useful
in
risk
management
decisions.
HED
notes
that
all
of
the
residential
scenarios
with
risk
estimates
of
concern,
including
the
aggregate
cancer
risk
estimate
are
considered
high
end
estimates
based
on
standard
HED
assumptions
and
a
100%
dermal
absorption
factor.
Data
Gaps
Most
pertinent
product
chemistry
data
requirements
are
satisfied
for
the
Rohm
and
Haas
94.6%
T/
TGAI,
and
51%
FI.
Some
additional
physical
chemistry
and
processing
information
are
required.
There
is
confidence
in
the
overall
scientific
quality
of
the
available
toxicity
data,
but
several
data
gaps
were
identified:
a
developmental
toxicity
study
in
rats,
a
21
day
dermal
toxicity
study,
28
day
inhalation
toxicity
study,
a
dermal
penetration
study
and
a
comparative
thyroid
rat
assay
in
adult
animals
and
offspring.
Some
label
amendments
and
data
submissions
are
required,
including
additional
residue
data
for
use
on
grasses,
dried
winter
peas
(outstanding),
the
vines
and
hay
of
winter
peas,
grass
forage,
and
hay.
The
registrant
is
required
to
improve
the
analytical
method
for
animal
residue
data;
and
to
submit
bridging
independent
laboratory
validation
data.
Additional
confirmatory
storage
stability
data
for
the
regulated
pronamide
metabolites
on
alfalfa,
apples,
grapes,
lettuce,
and
peaches
or
plums
are
required.
8
Cl
Cl
O
N
H
CH
3
CH
3
CH
2.0
PHYSICAL
CHEMICAL
PROPERTIES
CHARACTERIZATION
The
chemical
name
for
pronamide
is
[3,5
dichloro
N(
1,1
dimethyl
2
propynyl)
benzamide].
The
chemical
structure
is
Empirical
Formula:
C12H11NOCl2
Molecular
Weight:
256.13
CAS
Registry
No.:
23950
58
5
PC
Code:
101701
Technical
pronamide
is
a
white
crystalline
solid
with
a
melting
point
of
155
156
°C,
specific
gravity
of
0.48
g/
cc,
octanol/
water
partition
coefficient
(log
POW)
of
3.05
3.27,
and
vapor
pressure
of
8.50
x
10
5
torr
at
25
°C.
Because
of
its'
low
vapor
pressure,
pronamide
is
not
expected
to
present
an
inhalation
exposure
risk
when
used
outdoors.
There
are
no
toxicologically
significant
impurities
in
the
manufacturing
process.
3.0
HAZARD
CHARACTERIZATION
The
active
ingredient
pronamide
appears
to
be
a
liver
toxicant.
Adverse
liver
related
effects
(increases
in
liver
weight
and/
or
liver
related
serum
enzymes
and/
or
histopathology)
were
consistently
observed
in
every
animal
species
studied.
Other
target
organs
included
the
thyroid,
testes
and
pituitary
in
rats,
and
the
kidneys,
adrenal
glands,
thymus,
heart,
testes,
and
brain
in
dogs.
3.1
Hazard
Profile
Acute
Toxicity
The
acute
toxicity
data
base
for
pronamide
technical
is
considered
complete.
No
additional
studies
are
required
at
this
time.
Pronamide
technical
has
a
low
order
of
acute
toxicity
via
the
oral,
dermal,
and
inhalation
routes
of
exposure
(Toxicity
Category
III
or
IV),
produces
mild
irritation
to
the
eyes
and
skin
(Toxicity
Category
IV),
and
is
not
a
dermal
sensitizer.
The
acute
toxicity
data
for
pronamide
is
summarized
below
in
Table
1.
9
Table
1.
Acute
Toxicity
of
Pronamide
(Propyzamide)
Guideline
Number
Study
Type
MRID
Number
Results
Toxicity
Category
870.1100
(§
81
1)
Acute
Oral
Rat,
>
92.0%
a.
i.
00085505
LD50
(males
and
females)
is
greater
than
5000
mg/
kg
IV
870.1100
(§
81
1)
Acute
Oral
(Limit
test)
Rat
95.7%
a.
i.
43583901
LD50
(males
and
females)
is
greater
than
5000
mg/
kg
IV
870.1200
(§
81
2)
Acute
Dermal
(Limit
Test)
Rabbit,
95.7%
a.
i.
43583902
LD50
(males
and
females)
is
greater
than
2000
mg/
kg
III
870.1300
(§
81
3)
Acute
Inhalation
Rat,
95.7%
a.
i.
44034201
LC50
is
greater
than
2.1
mg/
L
following
a
4
hour
exposure
III
870.2400
(§
81
4)
Primary
Eye
Irritation
Rabbit
95.7%
a.
i.
43583904
Mild
occular
irritant
IV
870.2500(§
81
5)
Primary
Dermal
Irritation
Rabbit,
95.7%
a.
i.
43583903
Slight
dermal
irritant
IV
870.2600
(§
81
6)
Dermal
Sensitization
Guinea
pig,
>
92.0%
a.
i.
00062605
Not
a
sensitizer
N/
A
Subchronic
Toxicity
The
data
base
for
subchronic
toxicity
is
considered
incomplete.
The
HIARC
identified
two
subchronic
toxicity
study
data
gaps
and
recommended
the
following
studies
be
conducted
in
order
fulfill
the
requirements
cited
for
a
food/
feed
use
chemical
(40
CFR
158.340):
1)
a
21
day
dermal
toxicity
study
(guideline
870.3200;
old
82
2);
and
2)
a
28
day
inhalation
toxicity
study
(non
guideline)
However,
the
pronamide
subchronic
data
base
does
contain
two
acceptable
studies
conducted
in
the
rat
that
can
be
used
for
regulatory
purposes;
a
4
week
oral
toxicity
study
(non
guideline)
and
a
13
week
oral
toxicity
study
(guideline).
In
the
non
guideline,
4
week
study,
systemic
toxicities
were
noted
in
males
treated
with
37.24
or
74.05
mg/
kg/
day
pronamide
and
in
females
treated
with
43.65
or
87.65
mg/
kg/
day
pronamide.
These
toxicities
were
limited
to
the
liver
and
included
increases
in
absolute
and
relative
(to
body)
liver
weights
(males:
both
doses;
females:
high
dose)
and
a
positive
trend
in
the
increased
incidence
of
centrilobular
hypertrophy
(males).
When
pronamide
was
administered
in
the
diet
for
13
consecutive
weeks,
male
rats
treated
with
60.0
mg/
kg/
day
and
females
rats
treated
with
74.6
mg/
kg/
day
presented
with
the
following
systemic
toxicities
in
one
or
both
sexes:
decreased
body
weight,
body
weight
gain
and
food
consumption,
increased
blood
cholesterol
levels,
increased
relative
(to
body)
liver
weights
and
incidence
of
hepatic
centrilobular
hypertrophy.
At
the
highest
dose
tested
(254.0
mg/
kg/
day
for
males
and
289.2
mg/
kg/
day
in
females),
many
of
these
toxicities
were
observed
in
both
10
sexes
and
showed
an
increase
in
incidence
and/
or
severity.
The
following
additional
changes
were
also
observed
in
high
dose
animals:
clinical
signs
(brown
and/
or
yellow
staining
of
the
anogenital
area
(males),
increased
enzyme
activity
(SGOT
and
alkaline
phosphatase)
in
males,
triglyceride
blood
levels
(females),
increased
absolute
liver
weights
(males
and
females),
and
increased
incidences
of
thyroid
follicular
cell
hypertrophy
(males
and
females)
sexes
and
anterior
pituitary
cellular
hypertrophy
(males).
After
4
weeks
of
recovery,
most
of
the
adverse
effects
observed
at
the
high
dose
were
partially
or
completely
reversed
with
the
exception
of
the
increase
in
incidence
of
pituitary
cellular
hypertrophy
(males
only).
Reproductive
&
Developmental
Toxicity
There
was
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
in
the
fetuses
or
the
offspring
of
rats
or
rabbits
following
pre
and/
or
postnatal
exposure
to
pronamide.
Fetal/
offspring
effects
in
both
of
these
species
were
observed
at
either
the
same
or
higher
dose
levels
which
produced
maternal/
parental
toxicity.
In
the
developmental
toxicity
study
in
rabbits,
abortions
were
observed
at
a
higher
dose
level
(80
mg/
kg/
day)
compared
to
the
dose
(20
mg/
kg/
day)
at
which
maternal
toxicity
(soiled
anal
area,
anorexia
and
punctate
vacuolation
of
hepatocytes)
was
observed.
Also,
no
evidence
of
increased
susceptibility
was
demonstrated
in
the
two
generation
reproduction
study
in
rats.
Offspring
toxicity
(decreased
combined
male/
female
pup
weight/
litter)
was
observed
at
the
same
dose
that
caused
parental
toxicity
(decreased
body
weight
and
food
consumption
in
both
sexes,
increased
incidences
of
histopathology
of
the
liver,
adrenal
gland,
thyroid
gland,
and
anterior
pituitary
gland
in
both
P1
and
P2
generations,
and
increased
incidences
of
uterine
gross
pathology
in
P2
females).
Parental
and
offspring
toxicities
were
observed
at
the
same
LOAEL
of
1500
ppm
(130.1
mg/
kg/
day
for
males
and
120.7
mg/
kg/
day
for
females).
Evidence
for
susceptibility
could
not
be
ascertained
in
the
developmental
toxicity
study
conducted
in
rats.
No
toxicities
were
observed
in
either
maternal
animals
or
fetuses
at
any
dose
tested
(5
160
mg/
kg/
day);
a
LOAEL
could
not
be
established
in
the
rat
developmental
toxicity
study.
Since
this
study
failed
to
provide
evidence
concerning
the
potential
increased
susceptibility
to
infants
and
children
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996,
a
repeat
developmental
toxicity
study
in
the
rat
is
required
to
fulfill
the
OPPTS
harmonized
test
guideline
870.3700.
Chronic
Toxicity:
Following
chronic
exposure
(mid
dose
and/
or
high
dose
groups;
33.1
mg/
kg/
day
and/
or
67.7
mg/
kg/
day)
in
dogs,
systemic
toxicities
presented
as
decreased
body
weights,
body
weight
gains,
food
consumption,
serum
albumin,
platelet
counts,
increased
enzyme
activity
(alkaline
phosphatase,
alanine
aminotransferase,
and
gamma
glutamyltransferase),
increased
absolute
and/
or
relative
weights
of
the
thyroid,
liver,
heart,
testes,
adrenal
glands,
kidneys
and
thymus,
and
histopathology
of
the
liver
(hepatocytic
hypertrophy,
hyperplasia
and
granular
brown
pigmentation/
mononuclear
infiltration
of
Kupffer
cells)
and
kidneys
(granular
brown
pigment
in
the
epithelial
cells
of
the
proximal
convoluted
tubules).
In
rats,
the
toxicities
observed
included
decreased
body
weight/
body
weight
gain,
increased
liver
weight
and
histopathology
of
the
liver
(hypertrophy
accompanied
by
eosinophilic
cell
alteration),
thyroid
(follicular
cell
hypertrophy
and
hyperplasia),
and
ovaries
(sertoliform
tubular
hyperplasia)
at
42.59
mg/
kg/
day
(LOAEL).
In
the
carcinogenicity
study
conducted
in
mice,
systemic
toxicities
observed
at
the
LOAEL
of
75
mg/
kg/
day
were
limited
to
decreased
body
weight/
body
weight
gain,
increased
liver
weight
and
histopathology
of
the
liver
(hypertrophy,
nodules/
masses,
parenchymal
necrosis,
and
cholestasis).
Under
the
conditions
of
this
study,
there
was
evidence
of
a
treatment
related
increase
in
tumor
incidence
in
the
liver
of
male
mice
when
compared
to
controls.
Dosing
is
considered
adequate
to
assess
the
carcinogenic
potential
of
11
pronamide
based
on
liver
effects
(non
neoplastic
lesions
and
increased
weight).
Mutagenicity:
With
the
exception
of
one
gene
mutation
assay,
the
remaining
five
mutagenicity
studies
were
determined
to
be
acceptable
for
regulatory
purposes
(The
acceptable
studies
satisfy
the
1991
mutagenicity
guideline
requirements).
The
results
from
these
studies
indicate
that
pronamide
was
not
mutagenic
in
Salmonella
typhimurium,
Escherichia
coli
or
in
cultured
Chinese
hamster
lung
cells
and
did
not
produce
a
genotoxic
response
in
Bacillus
subtiltis
or
in
cultured
primary
rat
hepatocytes.
There
was
also
no
evidence
of
clastogenicity
in
cultured
Chinese
hamster
ovary
cells
and
pronamide
administration
did
not
result
in
the
induction
of
micronucleated
polychromatic
erythrocytes
in
bone
marrow
of
mice.
Overall,
the
data
suggest
that
pronamide
is
negative
for
mutagenicity
in
vitro
and
in
vivo.
Carcinogenicity:
The
Carcinogenicity
Peer
Review
Committee
(CPRC)
classified
Pronamide
as
a
group
B2
probable
human
carcinogen
with
inadequate
evidence
in
humans
(Memorandum:
E.
Rinde,
May
26,
1993).
This
decision
was
based
on
the
finding
of
two
types
of
tumors
in
the
rat
(benign
testicular
interstitial
cell
tumors
and
uncommon
thyroid
follicular
cell
adenomas),
and
one
type
of
tumor
in
the
mouse
(hepatocellular
carcinomas).
A
linear,
low
dose
approach
(Q1*)
is
used
for
human
risk
characterization
and
the
tumor
incidence
data
used
in
this
calculation
is
derived
from
the
1982
mouse
carcinogenicity
study
(MRID
00114114,
00151822).
The
most
potent
unit
risk
Q1*,
based
on
male
mouse
liver
adenoma
and/
or
carcinoma
combined
tumor
rates,
is
2.59
x
10
2
(mg/
kg/
day)
1
in
human
equivalents
[converted
from
animal
to
humans
by
use
of
the
(mg/
kg
body
weight)
3/
4
interspecies
scaling
factor]
(Memorandum:
L.
Brunsman,
October
26,
2001).
Neurotoxicity:
Mammalian
neurotoxicity
studies
for
pronamide
have
not
been
conducted.
However,
since
pronamide
does
not
belong
to
a
class
of
chemicals
known
to
exhibit
neurotoxicity,
and
there
is
no
evidence
of
neurotoxicity
seen
in
any
of
the
existing
studies,
neurotoxicity
studies
(e.
g.,
an
acute
delayed
neurotoxicity
study
in
the
hen,
a
neurotoxicity
screening
battery
or
a
developmental
neurotoxicity
study)
were
not
required.
Metabolism:
Pronamide
is
rapidly
absorbed
from
the
gastrointestinal
tract
and
extensively
and
rapidly
metabolized;
93
103%
the
radioactivity
administered
was
recovered
.
It
is
excreted
(7
days
post
dosing)
equally
in
both
the
urine
(40
61%)
and
the
feces
(40
60%).
No
bioaccumulation
was
apparent;
radioactivity
recovered
in
all
tissues
were
consistently
highest
at
the
first
sampling
time
(8
hours
postdose
then
gradually
declined
to
insignificant
levels
7
days
after
dosing.
The
elimination
of
radioactivity
from
the
plasma
of
low
dose
rats
was
biphasic
[rapid
phase
=
12.6
hrs
(males)
and
12.7
hrs
(females);
slow
phase
=
36.6
hrs
(males)
and
45.3
hrs
(females)]
and
that
of
the
high
dose
rats
was
monophasic
[t½
=
24.1
hrs
(males)
and
24.8
hrs
(females)].
Tissues
with
the
highest
radioactivity
contents
were,
in
decreasing
order,
the
fat,
adrenals,
bone
marrow,
thyroids,
liver,
kidney,
and
plasma.
Very
little
unchanged
pronamide
was
recovered
in
the
urine
and
no
significant
difference
in
the
urinary
metabolite
profile
was
observed
between
the
doses
or
the
sexes.
Approximately
27
unidentified
metabolites
were
found
in
the
urine
and
none
exceeded
3.3%
of
the
dose
whereas
all
of
the
fecal
metabolites
were
unidentified
and
comprised
less
than
1%
of
the
dose.
Two
major
urinary
metabolites
have
been
identified
and
quantified;
2(
3,5
dichlorophenyl)
4,4
dimethyl
5
carboxyoxazoline
(metabolite
SS47
70,
3.0
5.9%
of
the
administered
dose)
and
N
carboxymethyl
3,5
dichlorobenzamide
(metabolite
10,
12.7
18.9%
of
the
administered
dose).
Dermal
Absorption/
Toxicity:
No
dermal
penetration
study
conducted
with
pronamide
technical
is
available
in
the
toxicity
data
base.
A
dermal
penetration
study
conducted
with
the
Kerb
50W
and
3.3F
12
pronamide
formulations
was
submitted,
however,
this
study
was
classified
as
unacceptable
guideline
(the
actual
doses
applied
to
the
skin
were
not
determined
and
there
were
discrepancies
in
the
percent
radioactive
recovery).
In
addition,
there
were
no
dermal
toxicity
studies
submitted
which
could
be
used
for
comparison
to
oral
toxicity
studies.
Therefore,
a
100%
(default
value)
dermal
absorption
factor
was
determined
for
risk
assessment
purposes.
A
repeat
dermal
penetration
study
in
the
rat
is
required
to
fulfill
the
OPPTS
harmonized
test
guideline
870.7600.
Endocrine
Effects:
Pronamide
is
an
organochlorine
herbicide
which
has
been
identified
by
the
Agency's
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(EDSTAC)
as
a
potential
endocrine
disruptor.
Evidence
of
endocrine
effects
from
several
guideline
toxicity
studies
as
well
as
two
special
studies
submitted
to
the
Agency
by
the
Registrant
include,
in
part:
(i)
histopathology
of
the
thyroid
gland,
pituitary
gland,
adrenal
glands,
testes
and
ovaries,
(ii)
changes
in
hormone
levels;
decreased
T4
and
increased
TSH,
LH
and
FSH,
and
(iii)
the
induction
of
enzymes
such
as
cytochrome
P450
and
B5,
and
NADPH
cytochrome
c
reductase
in
addition
to
those
enzymes
involved
in
the
oxidation
of
testosterone.
Two
special
studies
were
conducted
by
the
Registrant
to
evaluate
pronamide's
effect
on
hormonal
balance
in
support
of
a
threshold
mechanism
for
the
induction
of
thyroid
and
testicular
neoplasms.
Although
the
results
of
these
special
endocrine
studies
are
suggestive
of
a
pronamide
induced
thyroid
and
testicular
neoplastic
effect
via
disruption
of
the
pituitary
thyroid
and
pituitary
testis
hormonal
balance,
these
data
are
far
from
conclusive.
Based
on
the
absence
of
any
additional
information
as
well
as
the
Mechanism
of
Toxicity
Assessment
Review
Committee's
(MTARC)
evaluation
of
the
existing
pronamide
toxicology
data
base
(Memorandum:
M.
Centra,
January
21,
2001)
and
the
Agency's
previous
hazard
characterization
of
this
active
ingredient
(Memorandum:
N.
Thoa,
May
26,
1993),
it
was
determined
that
the
postulated
threshold
mechanism
for
the
induction
of
thyroid
and
testicular
neoplasms
is
not
supported
by
the
available
data.
Therefore,
HED
has
recommended
that
additional
studies
be
conducted
with
pronamide
to
determine
its
mechanism
of
endocrine
toxicity.
One
such
study,
a
comparative
assay
in
the
rat
that
is
designed
to
assess
thyroid
function
in
adult
animals
and
their
offspring
as
well
as
potential
central
nervous
system
effects
in
the
young,
is
required
because
of
the
endocrine
toxicities
observed
in
various
organ
systems
(thyroid
gland,
testes,
ovaries,
adrenal
glands,
pituitary
gland)
of
rats
and/
or
dogs.
The
toxicity
study
profile
is
summarized
in
Table
2.
TABLE
2.
Subchronic,
Chronic
and
Other
Toxicity
Profiles
for
Pronamide
(Propyzamide
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification/
Doses
Results
870.3100
(§
82
1a)
4
Week
Oral
Toxicity
Rat
MRID
42669402
(6/
18/
87)/
Acceptable
Nonguideline
ppm
=
0,
500,
or
1000
mg/
kg/
day
(males)
=
0,
37.24,
or
74.05
mg/
kg/
day
(females)
=
0,
43.65,
or
87.65
NOAEL
=
less
than
500
ppm
(37.24
mg/
kg/
day
for
males;
43.65
mg/
kg/
day
for
females)
LOAEL
=
less
than
or
equal
to
1000
ppm
(74.05
mg/
kg/
day
for
males;
87.65
mg/
kg/
day
for
females)
based
upon
increased
absolute
and
relative
(to
body)
liver
weights
in
males
and
females
and
a
positive
trend
in
increased
incidence
of
liver
centrilobular
hypertrophy
in
males.
TABLE
2.
Subchronic,
Chronic
and
Other
Toxicity
Profiles
for
Pronamide
(Propyzamide
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification/
Doses
Results
13
870.3100
(§
82
1a)
90
Day
Oral
Toxicity
Rat
MRID
42669403
(11/
2/
67)/
Acceptable
Guideline
ppm
=
0,
40,
200,
1000,
or
4000
mg/
kg/
day
(males)
=
0,
2.5,
12.3,
60.0,
or
254.0
mg/
kg/
day
(females)
=
0,
3.1,
15.0,
74.6,
or
289.2
NOAEL
(males
and
females)
=
200
ppm
(12.3
mg/
kg/
day
in
males;
15.0
mg/
kg/
day
in
females)
LOAEL
=
1000
ppm
(60.0
mg/
kg/
day
in
males;
74.6
mg/
kg/
day
in
females)
based
upon
increased
relative
liver
weights
and
increased
incidence
of
centrilobular
hypertrophy
of
the
liver
in
both
sexes,
decreased
body
weight,
body
weight
gain
and
food
consumption
in
females
and
increased
blood
cholesterol
levels
in
males.
870.3700
(§
83
3a)
Developmental
Toxicity
Rat
MRID
40334501
(7/
10/
87)/
Unacceptable
Guideline
(not
upgradeable)
mg/
kg/
day
=
0,
5,
20,
80,
or
160
Maternal
Toxicity
NOAEL
=
greater
than
or
equal
to
160
mg/
kg/
day
LOAEL
=
greater
than
160
mg/
kg/
day
(highest
dose
tested;
LOAEL
not
established)
Developmental
Toxicity
NOAEL
=
greater
than
or
equal
to
160
mg/
kg/
day
LOAEL
=
greater
than
160
mg/
kg/
day
(highest
dose
tested;
LOAEL
not
established)
870.3700
(§
83
3b)
Developmental
Toxicity
Rabbit
MRID
00148065,
00148064
(6/
4/
85
)/
Acceptable
Guideline
mg/
kg/
day
=
0,
5,
20,
or
80
Maternal
Toxicity
NOAEL
=
5
mg/
kg/
day
LOAEL
=
20
mg/
kg/
day
based
upon
clinical
signs
of
toxicity
(soiled
anal
area,
anorexia
and
punctate
vacuolation
of
hepatocytes)
and
liver
effects
(hepatocellular
necrosis,
eosinophilia,
swelling
of
hepatocytes,
pigmentation
of
Kupffer
cells).
Developmental
Toxicity
NOAEL
=
20
mg/
kg/
day
LOAEL
=
80
mg/
kg/
day
based
upon
abortions.
870.3800
(§
83
4)
Multigeneration
Reproductive
Toxicity
Rat
MRID
41540301
(1968)/
Acceptable
guideline
ppm
=
0,
40,
200,
or
1500
mg/
kg/
day
(males)
=
0,
3.1,
16.0,
or
120.7
mg/
kg/
day
(females)
=
0,
3.6,
18.0,
or
130.1
Parental/
Systemic
Toxicity
NOAEL
=
200
ppm
(16.0
mg/
kg/
day
for
females
and
18.0
mg/
kg/
day
for
males)
LOAEL
=
1500
ppm
(120.7
mg/
kg/
day
for
females
and
130.1
mg/
kg/
day
for
males)
based
upon
decreases
in
body
weight
and
feed
consumption
in
both
sexes
and
increased
incidences
of
histology
of
the
liver
(centrilobular
hepatocyte
hypertrophy;
both
sexes),
adrenal
glands
(zona
glomerulosa
cellular
hypertrophy;
both
sexes),
thyroid
gland
(follicular
cell
hypertrophy;
females),
and
anterior
pituitary
gland
(cellular
hypertrophy;
males)
in
both
P1
and
P2
generations,
and
increased
incidences
of
uterine
gross
pathology
(black
foci/
serosal
surface)
in
P2
females.
Reproductive
Toxicity
NOAEL
=
greater
than
or
equal
to
1500
ppm
LOAEL
=
greater
than
1500
ppm;
not
established
TABLE
2.
Subchronic,
Chronic
and
Other
Toxicity
Profiles
for
Pronamide
(Propyzamide
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification/
Doses
Results
14
870.4100
(§
83
1b)
Chronic
Toxicity
Dog
MRID
41807601,41807602,
4213030
(8/
5/
68)/
Acceptable
Guideline
ppm
=
0,
300,
875,
or
1750
mg/
kg/
day
(males)
=
0,
11.9,
33.1,
or
67.7
mg/
kg/
day
(females)
=
0,
11.9,
36.1,
or
69.0
NOAEL
(males,
females)
=
300
ppm
(11.9
mg/
kg/
day)
LOAEL
=
875
ppm
(33.1
mg/
kg/
day
in
males;
36.1
mg/
kg/
day
in
females)
based
upon
increased
serum
alkaline
phosphatase
(males),
increased
thyroid
and
liver
weights
(females),
and
increased
incidence
in
liver
histopathology
(males
and
females;
increased
incidence
of
hepatocyte
hypertrophy,
granular
pigmentation,
mononuclear
infiltration,
and
granular
brown
pigmentation
in
Kupffer
cells).
870.4300
(§
83
1/
2a/
5)
Combined
Chronic
Toxicity/
Carcinogenicity
Rat
MRID
41714001,
41714002
(10/
1/
90)/
Acceptable
Guideline
ppm
=
0,
40,
200,
or
1000
mg/
kg/
day
(males)
=
0,
1.73,
8.46,
or
42.59
mg/
kg/
day
(females)
=
0,
2.13,
10.69,
or
55.09
NOAEL
(males
and
females)
=
200
ppm
(8.46
mg/
kg/
day
in
males;
1069
mg/
kg/
day
in
females)
LOAEL
=
1000
ppm
(42.59
mg/
kg/
day
in
males;
55.09
mg/
kg/
day
in
females)
based
upon
increased
relative
liver
weight
and
the
non
neoplastic
histologic
changes
in
the
liver
(centrilobular
hypertrophy
and
hepatocellular
eosinophilic
alteration
in
males
and
females),
thyroid
(follicular
cell
hypertrophy
in
males
and
females)
and
ovaries
(sertoliform
tubular
hyperplasia
in
females).
Rats
fed
diets
containing
1000
ppm
pronamide
showed
an
increased
incidence
of
thyroid
follicular
cell
adenomas
in
male
and
female
rats
and
benign
testicular
interstitial
cell
tumors
in
male
rats.
There
was
no
progression
of
tumors
to
carcinomas.
Under
the
conditions
of
this
study,
the
dosing
was
considered
to
be
adequate
based
upon
decreased
body
weight
gain
and
the
non
neoplastic
histologic
changes
in
the
liver.
TABLE
2.
Subchronic,
Chronic
and
Other
Toxicity
Profiles
for
Pronamide
(Propyzamide
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification/
Doses
Results
15
870.4200
(§
83
2b)
Carcinogenicity
Mouse
MRID
00107968
(1974)/
Although
this
study
would
not
normally
meet
the
guideline
requirement
for
a
carcinogenicity
study
(870.4300)
in
this
species
(i.
e.,
study
deficiencies
included
lack
of
dietary
analyses
and
food
consumption
to
ensure
homogeneity,
stability,
and
concentration
of
test
material
in
the
diet,
and
to
assess
potential
palatability
problems
with
the
diet),
confidence
in
the
reported
tumor
data
is
enhanced
by
the
findings
of
a
subsequent
1982
special
carcinogenicity
study
in
male
mice
(MRID
00114114)
that
confirm
the
tumor
findings.
If
reviewed
in
conjunction
with
the
1982
study,
the
present
study
is
adequate
to
assess
the
carcinogenic
potential
of
pronamide
in
mice
and
it
can
be
used
for
regulatory
and
risk
assessment
purposes.
ppm
=
0,
1000,
or
2000
mg/
kg/
day
=
0,
150,
or
300
NOAEL
(males,
females)
=
not
established
LOAEL
=
1000
ppm
(150
mg/
kg/
day)
based
upon
decreases
in
body
weight
gain
in
high
dose
females
and
increases
in
relative
(to
body)
weight
of
the
liver
in
both
sexes.
Male
and
female
B6C3F1
mice
fed
diets
containing
pronamide
for
18
months
showed
a
dose
related
increase
in
the
incidence
of
hepatocellular
carcinomas
in
male
mice.
Pronamide
did
not
induce
hepatocellular
carcinomas
in
female
mice.
Under
the
conditions
of
this
study,
the
dosing
was
considered
to
be
adequate
based
upon
decreases
in
body
weight
gain
in
high
dose
females
and
increases
in
relative
(to
body)
weight
of
the
liver
in
both
sexes
at
doses
greater
than
or
equal
to
1000
ppm.
870.4300
(§
83
1/
2a/
5)
Carcinogenicity
Mouse
(Males
)
MRID
00114114,
00151822
(1982)/
This
special
carcinogenicity
study
in
the
male
mouse
is
classified
as
AcceptableNonguideline
The
data
confirmed
the
results
of
a
previously
conducted
carcinogenicity
study
in
mice
(1974,
MRID
00107968).
When
reviewed
in
conjunction
with
the
1974
carcinogenicity
study,
these
two
studies
fulfill
the
guideline
requirement
for
a
carcinogenicity
study
[870.4200
(§
83
2b)]
in
mice
and
can
be
used
for
regulatory
and
risk
assessment
purposes.
ppm
=
0,
20,
100,
500,
or
2500
mg/
kg/
day
=
0,
3,
15,
75,
or
375
NOAEL
(males)
=
100
ppm
(15
mg/
kg/
day)
LOAEL
=
500
ppm
(75
mg/
kg/
day)
based
upon
gross
findings
(increased
incidences
of
hepatic
nodules/
masses
and
hepatic
enlargement)
observed
after
24
months
of
treatment.
870.5100
(§
84
2)
Gene
Mutation/
In
vitro
mammalian
cell
assay
in
Chinese
hamster
ovary
[CHO]
cells
MRID
40090601
(2/
10/
87)/
Unacceptable
Guideline
Fg/
plate
=
1,
10,
100
and
500
Negative.
Pronamide
did
not
induce
a
mutagenic
or
genotoxic
effect
in
Salmonella
typhimurium
strains
TA98,
TA100,
TA1535,
TA1537
and
TA1538
at
concentrations
of
1,
10,
100
and
500
Fg/
plate
±
S9
activation.
TABLE
2.
Subchronic,
Chronic
and
Other
Toxicity
Profiles
for
Pronamide
(Propyzamide
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification/
Doses
Results
16
870.5100
(§
84
2)
Gene
Mutation
in
Salmonella
typhimurium,
Bacillus
subtilis
and
Escherichia
coli
MRID
40090602
(8/
10/
78)/
Acceptable
Guideline
Escherichia.
coli
Fg/
plate
=
10
5000
Bacillus
subtilis
Fg/
disk
=
20
2000
Negative.
Pronamide
did
not
induce
a
mutagenic
or
genotoxic
effect
in
Salmonella
typhimurium
strains
TA98,
TA100,
TA1535,
TA1537
and
TA1538
or
WP2
hcr
of
Escherichia
coli
at
concentrations
of
10
5000
Fg/
plate
±
S9
activation.
Pronamide
did
not
induce
DNA
damage
in
Bacillus
subtilis
at
concentrations
of
20
2000
Fg/
disk.
870.5300
(§
84
2)
Gene
Mutation/
In
vitro
mammalian
cell
assay
in
Chinese
hamster
V79
cells
MRID
40211106
(10/
29/
84)/
Acceptable
Guideline
Fg/
ml
=
2.5,
5,
10,
20
and
40
Negative.
Pronamide
did
not
induce
a
mutagenic
effect
in
Chinese
hamster
V79
cells
at
[noncytotoxic]
concentrations
of
2.5,
5,
10,
20
and
40
Fg/
ml
±
S9
activation
following
a
48,
96
or
168
hour
incubation
period.
870.5300
(§
84
2)
Gene
Mutation/
In
vitro
mammalian
cell
assay
in
Chinese
hamster
ovary
[CHO]
cells
MRID
40211108
(2/
10/
87)/
Acceptable
Guideline
Fg/
ml
=
25,
50,
75,
100
and
150
Negative.
Pronamide
did
not
induce
a
mutagenic
effect
in
Chinese
hamster
ovary
cells
at
[noncytotoxic]
concentrations
of
25,
50,
75,
100
and
150
Fg/
ml
±
S9
activation.
870.5385
(§
84
2)
Cytogenetics/
In
vivo
cytogenetics
bone
marrow
assay
in
mice
MRID
40211105
(10/
31/
84)/
Acceptable
Guideline
g/
kg
=
0,
0.48,
1.94
or
4.94
Negative.
Pronamide
did
not
induce
any
structural
chromosomal
aberrations
in
bone
marrow
cells
of
male
mice
given
doses
of
0,
0.48,
1.94
or
4.94
g/
kg
in
either
acute
or
subacute
dosing
regimens.
870.5900
(§
84
2)
Other
Mutagenic
Mechanisms/
In
vitro
Unscheduled
DNA
Synthesis
in
primary
rat
hepatocytes
MRID
40211107
(2/
11/
87)/
Acceptable
Guideline
g/
ml
=
1,
5,
10,
25
or
50
Negative.
There
was
no
evidence
that
Pronamide
caused
unscheduled
DNA
synthesis
in
primary
rat
hepatocytes
at
concentrations
of
1,
5,
10,
25
or
50
g/
ml.
TABLE
2.
Subchronic,
Chronic
and
Other
Toxicity
Profiles
for
Pronamide
(Propyzamide
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification/
Doses
Results
17
870.7485
(§
85
1)
Metabolism
and
Phamacokinetics
Rat
MRID
41801801,
41929901
(2/
21/
91,
6/
25/
91)/
AcceptableGuideline
single
oral
dose
(2
or
100
mg/
kg)
or
multiple
low
doses
(20
ppm
a.
i.
in
the
diet
for
14
days)
followed
by
a
low
dose
(2
mg/
kg)
14
Cpronamide
Pronamide
is
rapidly
absorbed
and
completely
and
rapidly
eliminated.
Over
a
7
day
period,
most
of
the
radioactivity
administered
was
recovered
(93
103%)
in
the
urine
(40
61%)
and
feces
(40
60%).
Only
0.08
0.21
and
0.83
2.43
percent
of
the
administered
dose
were
recovered
in
tissues
and
carcasses,
respectively.
No
bioaccumulation
was
apparent;
radioactivity
recovered
in
all
tissues
were
consistently
highest
at
the
first
sampling
time
(8
hours
post
dose)
then
gradually
declined
to
insignificant
levels
7
days
after
dosing.
Tissues
with
the
highest
radioactivity
contents
were,
in
decreasing
order,
the
fat,
adrenals,
bone
marrow,
thyroids,
liver,
kidney,
and
plasma.
Very
little
unchanged
pronamide
was
recovered
in
urine.
Of
the
twenty
metabolites
found,
only
thirteen
(constituting
51.1%
of
the
total
radioactivity
in
urine)
were
clearly
identified.
The
feces
was
not
examined
for
metabolites.
However,
when
these
data
(MRID
41801801,
41929901)
are
reviewed
in
conjunction
with
the
characterization
of
the
urinary
and
fecal
metabolites
of
pronamide
(MRID
42858001),
the
guideline
requirement
for
a
metabolism
and
pharmacokinetics
study
[OPPTS
870.7485
(§
85
1)]
is
satisfied.
870.7485
(§
85
1)
Metabolism
and
Pharmacokinetics
Rat
MRID
42858001
(7/
15/
93)/
Acceptable
Guideline
single
oral
dose
(2
or
100
mg/
kg)
or
multiple
low
doses
(20
ppm
a.
i.
in
the
diet
for
14
days)
followed
by
a
low
dose
(2
mg/
kg)
14
Cpronamide
Urinary
and
fecal
metabolites
of
pronamide
were
identified
in
male
and
female
rats.
No
significant
difference
in
urinary
metabolite
profile
was
observed
between
sex
or
dose.
The
major
urinary
metabolites
were:
2(
3,5
dichlorophenyl)
4,4
dimethyl
5
carboxyoxazoline
(metabolite
SS47
70,
3.0
5.9%
of
the
administered
dose)
and
N
carboxymethyl
3,5
dichlorobenzamide
(metabolite
10,
12.7
18.9%
of
the
administered
dose).
In
the
urine,
approximately
27
unidentified
metabolites
were
found
and
none
exceeded
3.3%
of
the
dose.
In
contrast,
significant
differences
in
the
fecal
metabolite
profile
was
observed
between
doses.
Fecal
excretion
of
parent
ranged
from
9.2
10.9%
of
the
dose
for
the
low
dose
and
low
repeated
dose
groups
and
37.4
40.9%
for
the
high
dose
group.
In
the
feces,
almost
all
of
the
unidentified
metabolites
are
under
1%
of
the
dose.
The
metabolic
pathway(
s)
of
the
test
compound
have
been
postulated
in
rats.
This
study
adequately
describes
the
characterization
of
urinary
and
fecal
metabolites
of
pronamide
in
rats
following
lowand
high
dose
oral
and
repeated
oral
exposure.
When
these
data
(MRID
42858001)
are
reviewed
in
conjunction
with
previous
metabolism
studies
(MRID
41801801,
41929901),
the
guideline
requirement
for
a
metabolism
and
pharmacokinetics
study
[OPPTS
870.7485
(§
85
1)]
is
satisfied.
TABLE
2.
Subchronic,
Chronic
and
Other
Toxicity
Profiles
for
Pronamide
(Propyzamide
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification/
Doses
Results
18
870.7600
(§
85
3)
Dermal
Penetration
Rats
Kerb
50W
and
3.3F
formulations
only
MRID
40256701,
41117201
(4/
14/
87,
1/
27/
89)
UnacceptableGuideline
(not
upgradeable)
0.08
and
4.4
mg/
cm
2
The
dermal
absorption
rates
per
6
hours
were
19%
and
17%
for
50W
and
15.1%
and
5.4%
for
3.3F.
However,
these
data
are
based
on
a
normalization
of
numerical
values
rather
than
the
actual
results
obtained
from
the
study.
The
actual
doses
applied
to
the
skin
were
not
determined
and
there
were
discrepancies
in
recovery
for
the
50W
doses
(78%
and
122%
of
nominal
doses).
A
default
dermal
absorption
factor
of
100%
is
used
in
this
risk
assessment.
Non
Guideline
Thyroid
Function
and
Hepatic
Clearance
of
Thyroxine
in
Male
Rats.
This
non
guideline
study
was
submitted
to
the
Agency
as
an
addendum
to
the
chronic
toxicity/
carcinogenicity
study
in
rats
(MRID
41714001,
41714002)
MRID
42093401
(10/
9/
91)/
Acceptable
Nonguideline
ppm
=
0,
40,
1000,
or
4000
mg/
kg/
day
=
0,
3,
67
or
279
Systemic
and
Thyroid
Toxicity
NOAEL
=
40
ppm
(3
mg/
kg/
day)
LOAEL
=
1000
ppm
(67
mg/
kg/
day)
based
upon
decreases
in
body
weight
and
food
consumption,
increases
in
absolute
and/
or
relative
weight
of
the
liver
and
thyroid,
an
increase
in
serum
TSH
(at
4
weeks
but
not
at
13
weeks),
a
decrease
in
serum
T4,
and
an
increase
in
incidences
of
thyroid
and
pituitary
hypertrophy/
hyperplasia.
Non
Guideline
Effects
of
Endocrine
Regulation
of
the
Testis
in
Rats
Pilot
Study
MRID
42139601
(12/
6/
91)/
Acceptable
Nonguideline
ppm
=
0,
40,
1000,
or
4000
In
the
13
week
study,
Pronamide
treatment
(4000
ppm)
resulted
in
decreased
body
weight
(weeks
1
13)
and
food
consumption
(weeks
1
8),
increased
serum
LH
and
FSH
(respective
increases
at
4
and
13
weeks
were
60%
and
58%
for
FSH,
and
100%
and
77%
for
LH),
increased
absolute
and
relative
(to
body)
liver
weight,
increased
microsomal
protein
content,
increased
oxidation
of
testosterone,
increased
activity
of
cytochrome
P450
and
B5,
and
NADPH
cyochrome
creductase
increased
gross
pathology
of
the
liver
(enlarged/
dark),
increased
relative
(to
body)
testicular
weight,
and
increased
testicular
interstitial
cell
hyperplasia.
In
the
4
week
study,
alterations
in
clinical
chemistry
parameters
were
noted
only
at
4000
ppm
as
increases
in
sreum
LH
and
FSH.
These
effects
were
comparable
with
increases
observed
after
13
weeks.
3.2
FQPA
Considerations
On
December
3,
2001,
the
FQPA
Safety
Factor
Committee
evaluated
the
hazard
(See
Section
5.0,
Hazard
Characterization
and
Dose
Response
Assessment
Summary),
endocrine
(See
Section
9.0,
Endocrine
Disruption)
and
exposure
data
for
pronamide
and
made
the
recommendation
for
the
FQPA
safety
factor
to
be
used
in
human
health
risk
assessments
as
required
by
Food
Quality
Protection
Act
of
August
3,
1996.
(Memorandum:
C.
Christensen,
December
19,
2001).
19
Based
on
these
available
data,
the
FQPA
SF
Committee
determined
that
the
safety
factor
is
necessary
when
assessing
the
risk
posed
by
pronamide
because:
1.
There
is
evidence
of
endocrine
effects
(thyroid,
testes,
ovaries,
adrenal
glands,
pituitary
gland,
thymus)
identified
in
the
majority
of
studies
conducted
across
species.
A
special
study
designed
to
assess
thyroid
function
in
adult
animals
and
their
offspring
will
be
required.
However,
the
Committee
concluded
that
the
FQPA
safety
factor
could
be
reduced
to
3x
in
assessing
the
risk
posed
by
exposure
to
pronamide
because:
1.
The
toxicological
database
is
adequate
for
FQPA
assessment;
and,
2.
There
is
no
indication
of
quantitative
or
qualitative
increased
susceptibility
of
rabbits
to
in
utero
exposure
or
to
rats
following
pre/
post
natal
exposure.
Also,
in
the
available,
unacceptable
rat
study,
no
increased
susceptibility
was
seen
even
though
the
animals
could
have
tolerated
higher
doses.
3.
A
developmental
neurotoxicity
study
is
not
required;
and,
4.
The
dietary
(food
and
drinking
water)
and
residential
exposure
assessments
will
not
underestimate
the
potential
exposures
for
infants
and
children.
The
3x
FQPA
safety
factor
for
pronamide
is
applicable
to
all
population
subgroups
when
assessing
dietary
and
residential
exposure
scenarios
because
of
evidence
of
endocrine
effects.
The
FQPA
safety
factor
was
not
applied
to
the
acute
dietary
endpoint
because
no
appropriate
endpoint
was
available
to
quantitate
risk
to
either
the
general
population
or
to
females13
50
years
of
age
from
a
single
dose
administration
of
pronamide.
A
MOE
of
300
(10x
for
interspecies
extrapolation,
10x
for
interspecies
variation
and
a
3x
FQPA
safety
factor)
is
required
for
short
term,
intermediate
and
long
term
incidental
oral,
dermal,
and
inhalation
risk
assessments.
Therefore,
short
term,
intermediate
to
long
term
risk
estimates
with
a
MOE
$
300
do
not
exceed
the
HED
level
of
concern.
3.3
Hazard
Endpoint
Selection
The
strengths
and
weaknesses
of
the
pronamide
toxicology
database
were
considered
during
the
process
of
toxicity
endpoint
and
dose
selection.
20
Table
3.
Summary
of
Toxicological
Dose
and
Endpoints
for
Pronamide
for
Use
in
Human
Risk
Assessment
1
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
females
13
50
years
of
age
and
the
general
population
including
infants
and
children
No
appropriate
acute
dietary
endpoints
were
available
to
quantify
risk
to
females
13
50
years
of
age
or
to
the
general
population
from
a
single
dose
administration
of
pronamide.
The
adverse
effect
observed
in
the
rabbit
developmental
toxicity
study,
abortions,
were
not
considered
to
occur
after
a
single
dose
because
they
were
observed
in
rabbits
during
the
postdosing
phase
of
the
study
(days
22
24).
Therefore,
no
acute
dietary
endpoints
were
selected
which
represented
toxicities
from
a
single
dose
exposure.
Chronic
Dietary
all
populations
NOAEL
=
8.46
mg/
kg/
day
UF
=
100
Chronic
RfD
=
0.08
mg/
kg/
day
FQPA
SF
=
3
cPAD
=
chronic
RfD
FQPA
SF
=
0.027
mg/
kg/
day
Combined
Chronic
Toxicity/
Carcinogenicity
Study
Rat
LOAEL
=
42.59
mg/
kg/
day
based
on
increased
relative
(to
body)
liver
weight
and
non
neoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries.
Short
Term
Oral
(1
30
days)
(Residential)
oral
study
NOAEL
=
8.46
mg/
kg/
day
LOC
for
MOE
=
300
(Residential,
includes
the
FQPA
SF)
Developmental
Toxicity
Study
Rabbit
LOAEL
=
20
mg/
kg/
day
based
on
Clinical
signs
of
toxicity
(soiled
anal
area
and
anorexia)
and
liver
effects
(punctate
vacuolation
of
hepatocytes).
Intermediate
Term
Oral
(1
6
months)
(Residential)
oral
study
NOAEL
=
8.46
mg/
kg/
day
LOC
for
MOE
=
300
(Residential,
includes
the
FQPA
SF)
Combined
Chronic
Toxicity/
Carcinogenicity
Study
Rat
LOAEL
=
42.59
mg/
kg/
day
based
on
increased
relative
(to
body)
liver
weight
and
non
neoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries.
Short
Term
Dermal
(1
30
days)
(Occupational/
Resi
dential)
oral
study
NOAEL
=
8.46
mg/
kg/
day
dermal
absorption
rate
$
=
100%
LOC
for
MOE
=
300
(Residential,
includes
the
FQPA
SF)
Developmental
Toxicity
Study
Rabbit
LOAEL
=
20
mg/
kg/
day
based
on
Clinical
signs
of
toxicity
(soiled
anal
area
and
anorexia)
and
liver
effects
(punctate
vacuolation
of
hepatocytes).
IntermediateTerm
Dermal
(1
6
months)
(Occupational/
Resi
dential)
oral
study
NOAEL
=
8.46
mg/
kg/
day
dermal
absorption
rate
$
=
100%
LOC
for
MOE
=
300
(Residential,
includes
the
FQPA
SF)
Combined
Chronic
Toxicity/
Carcinogenicity
Study
Rat
LOAEL
=
42.59
mg/
kg/
day
based
on
increased
relative
(to
body)
liver
weight
and
non
neoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries.
Long
Term
Dermal
(6
months
lifetime
(Occupational/
Resi
dential)
oral
study
NOAEL
=
8.46
mg/
kg/
day
dermal
absorption
rate
$
=
100%
LOC
for
MOE
=
300
(Residential,
includes
the
FQPA
SF)
Combined
Chronic
Toxicity/
Carcinogenicity
Study
Rat
LOAEL
=
42.59
mg/
kg/
day
based
on
increased
relative
(to
body)
liver
weight
and
non
neoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries.
Table
3.
Summary
of
Toxicological
Dose
and
Endpoints
for
Pronamide
for
Use
in
Human
Risk
Assessment
1
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
21
Short
Term
Inhalation
(1
30
days)
(Occupational/
Resi
dential)
oral
study
NOAEL
=
8.46
mg/
kg/
day
inhalation
absorption
rate
$
=
100%
LOC
for
MOE
=
300
(Residential,
includes
the
FQPA
SF)
Developmental
Toxicity
Study
Rabbit
LOAEL
=
20
mg/
kg/
day
based
on
Clinical
signs
of
toxicity
(soiled
anal
area
and
anorexia)
and
liver
effects
(punctate
vacuolation
of
hepatocytes).
IntermediateTerm
Inhalation
(1
6
months)
(Occupational/
Resi
dential)
oral
study
NOAEL
=
8.46
mg/
kg/
day
inhalation
absorption
rate
$
=
100%
LOC
for
MOE
=
300
(Residential,
includes
the
FQPA
SF)
Combined
Chronic
Toxicity/
Carcinogenicity
Study
Rat
LOAEL
=
42.59
mg/
kg/
day
based
on
increased
relative
(to
body)
liver
weight
and
non
neoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries.
Long
Term
Inhalation
(6
months
lifetime)
(Occupational/
Resi
dential)
oral
study
NOAEL
=
8.46
mg/
kg/
day
inhalation
absorption
rate
$
=
100%
LOC
for
MOE
=
300
(Residential,
includes
the
FQPA
SF)
Combined
Chronic
Toxicity/
Carcinogenicity
Study
Rat
LOAEL
=
42.59
mg/
kg/
day
based
on
increased
relative
(to
body)
liver
weight
and
nonneoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries.
Cancer
(oral,
dermal,
inhalation)
Group
B2
"Probable
human
carcinogen"
Q1*
=
2.59
x
10
2
(mg/
kg/
day)
1
Cancer
classification
based
on
thyroid
follicular
cell
adenomas
(males
and
females)
and
benign
interstitial
cell
tumors
(males)
in
rats
and
hepatocellular
carcinomas
in
mice
(males).
1
UF
=
uncertainty
factor,
FQPA
SF
=
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
PAD
=
population
adjusted
dose
(a
=
acute,
c
=
chronic),
RfD
=
reference
dose,
LOC
=
level
of
concern,
MOE
=
margin
of
exposure,
Q1*
=
the
low
dose
linear
extrapolation
value
used
to
express
the
risk
to
the
human
population
for
development
of
cancer
following
exposure
to
pesticide
residues.
"
An
adjusted
dose
of
8.46
mg/
kg/
day
was
established
for
use
in
this
risk
assessment
based
on
a
maternal
toxicity
NOAEL
of
5
mg/
kg/
day
and
clinical
signs
of
toxicity
(soiled
anal
area
and
anorexia)
and
liver
effects
(punctate
vacuolation
of
hepatocytes)
observed
at
the
LOAEL
of
20
mg/
kg/
day
in
the
developmental
toxicity
study
conducted
in
rabbits.
$
Since
an
oral
endpoint
was
selected,
a
dermal
absorption
factor
of
100%
(default
value)
and
an
inhalation
absorption
factor
of
100%
(default
value)
should
be
used
in
route
to
route
extrapolation.
Acute
Dietary
Risk
Assessment:
No
appropriate
acute
dietary
endpoints
were
available
to
quantify
risk
to
females
13
50
years
of
age
or
to
the
general
population
from
a
single
dose
administration
of
pronamide.
The
adverse
effect
observed
in
the
rabbit
developmental
toxicity
study,
abortions,
were
not
considered
to
occur
after
a
single
dose
because
they
were
observed
in
rabbits
during
the
postdosing
phase
of
the
study
(days
22
24).
Therefore,
no
acute
dietary
endpoints
were
selected
which
represented
toxicities
from
a
single
dose
exposure.
Chronic
Dietary
Risk
Assessment:
A
chronic
reference
dose
(cRfD)
of
0.08
mg/
kg/
day
was
determined
on
the
basis
of
the
two
year
chronic
toxicity/
carcinogenicity
study
in
rats
and
the
application
of
an
uncertainty
factor
of
100
(10x
for
inter
species
extrapolation
and
10x
for
intra
species
variation).
The
22
NOAEL
in
this
study
was
8.46
mg/
kg/
day
and
the
LOAEL
was
42.59
mg/
kg/
day
based
upon
increased
relative
liver
weight
and
the
non
neoplastic
histologic
changes
in
the
liver
(centrilobular
hypertrophy
and
hepatocellular
eosinophilic
alteration
in
males
and
females),
thyroid
(follicular
cell
hypertrophy
in
males
and
females)
and
ovaries
(sertoliform
tubular
hyperplasia
in
females).
The
3x
FQPA
safety
factor
was
applied
for
chronic
dietary
risk
assessment
because
there
is
evidence
of
endocrine
effects
(thyroid,
testes,
ovaries,
adrenal
glands,
pituitary
gland,
thymus)
identified
in
the
majority
of
subchronic/
chronic
studies
conducted
across
species.
The
chronic
population
adjusted
dose
is
the
cRfD
adjusted
for
the
FQPA
safety
factor.
Therefore,
the
chronic
population
adjusted
dose
(cPAD)
is
0.027
mg/
kg/
day.
Short
Term
Incidental
Oral,
Dermal
and
Inhalation
Exposure
Risk
Assessments:
An
adjusted
dose
of
8.46
mg/
kg/
day
was
established
for
use
in
this
risk
assessment.
This
dose
selection
is
based
on
a
maternal
toxicity
NOAEL
of
5
mg/
kg/
day
and
the
clinical
signs
(soiled
anal
area
and
anorexia)
and
liver
effects
(punctate
vacuolation
of
hepatocytes)
observed
at
the
LOAEL
of
20
mg/
kg/
day
in
the
developmental
toxicity
study
conducted
in
rabbits.
Although
selection
of
this
study
for
short
term
exposure
scenarios
is
appropriate
for
the
route
(oral)
and
duration
(13
days),
the
NOAEL
of
5
mg/
kg/
day
is
lower
than
the
NOAEL
(8.46
mg/
kg/
day)
established
in
the
chronic
toxicity/
carcinogenicity
study
in
the
rat.
The
apparent
disparity
between
these
NOAELs
is
driven
by
the
doses
of
pronamide
selected
for
testing
in
these
studies.
The
HIARC
concluded
that
using
a
more
realistic
NOAEL
of
8.46
mg/
kg/
day
rather
than
5
mg/
kg/
day
would
provide
a
sufficiently
protective
dose
for
risk
assessment.
The
3x
FQPA
safety
factor
was
also
applied
to
these
risk
assessments
because
of
the
evidence
of
endocrine
effects
in
the
pronamide
toxicity
data
base.
Intermediate
Term
Incidental
Oral,
Dermal
and
Inhalation
Exposure
Risk
Assessments:
A
NOAEL
of
8.46
mg/
kg/
day
was
selected
from
the
combined
chronic
toxicity/
carcinogenicity
study
conducted
in
the
rat.
This
NOAEL
is
based
on
increased
relative
liver
weight
and
the
non
neoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries
which
were
observed
at
the
LOAEL
of
42.59
mg/
kg/
day.
The
HIARC
determined
that
this
study
is
appropriate
for
the
(1
6
months)
intermediate
term
exposure
duration
because
(i)
the
organ
toxicities
(liver,
thyroid,
and
ovaries)
observed
in
the
24
month
study
occurred
as
early
as
6
months
and
continued
to
study
termination
and
(2)
this
NOAEL
(8.46
mg/
kg/
day)
is
numerically
close
to
the
NOAEL
of
12.3
mg/
kg/
day
established
in
the
90
day
subchronic
toxicity
study
conducted
in
the
rat.
Although
the
90
day
subchronic
study
in
rats
demonstrated
liver
toxicities
(increased
absolute
and
relative
liver
weights
and
hepatocellular
hypertrophy)
at
a
LOAEL
of
60
mg/
kg/
day,
these
effects
were
considered
minimal.
Therefore
the
developmental
NOAEL
12.3
mg/
kg/
day
is
not
recommended
for
this
exposure
scenario.
The
3x
FQPA
safety
factor
is
applicable
because
of
the
evidence
of
endocrine
effects
in
the
pronamide
toxicity
data
base.
Long
Term
Dermal
and
Inhalation
Exposure
Risk
Assessments:
The
NOAEL
of
8.46
mg/
kg/
day
was
also
selected
from
the
combined
chronic
toxicity/
carcinogenicity
study
in
rats
and
is
considered
appropriate
for
these
exposure
scenarios.
This
NOAEL
is
based
on
increased
relative
liver
weight
and
the
non
neoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries
which
were
observed
at
the
LOAEL
of
42.59
mg/
kg/
day.
The
3x
FQPA
safety
factor
is
applicable
because
of
the
evidence
of
endocrine
effects
in
the
pronamide
toxicity
data
base.
Dermal
and
Inhalation
Absorption:
Since
no
dermal
or
inhalation
toxicity
studies
were
submitted,
the
selected
endpoint
is
from
an
oral
study
of
the
appropriate
duration
of
exposure
and
a
100%
(default)
absorption
factor
was
applied
to
dermal
and
inhalation
exposure
routes.
23
Aggregating
doses:
For
short
term
exposure,
incidental
oral,
dermal,
and
inhalation
routes
can
be
aggregated
because
of
the
use
of
oral
equivalents
and
a
common
endpoint
(clinical
signs
of
toxicity
and
liver
effects).
For
intermediate
term
and
long
term
exposure,
incidental
oral,
dermal
and
inhalation
routes
can
be
aggregated
because
of
oral
equivalents
and
a
common
endpoint
(increased
relative
liver
weight
and
non
neoplastic
histologic
changes
in
the
liver,
thyroid,
and
ovaries).
3.4
Endocrine
Disruption
Many
chemicals
belonging
to
the
class
of
organochlorine
chemicals
are
known
to
produce
disruption
of
the
endocrine
system.
Pronamide
is
an
organochlorine
herbicide
which
has
been
identified
by
the
Agency's
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(EDSTAC)
as
a
potential
endocrine
disruptor.
Evidence
of
endocrine
effects
from
several
guideline
toxicity
studies
as
well
as
two
special
studies
submitted
to
the
Agency
by
the
Registrant
include,
in
part:
(i)
histopathology
of
the
thyroid
gland,
pituitary
gland,
adrenal
glands,
testes
and
ovaries,
(ii)
changes
in
hormone
levels;
decreased
T4
and
increased
TSH,
LH
and
FSH,
and
(iii)
the
induction
of
enzymes
such
as
cytochromeP450
and
B5,
and
NADPH
cytochrome
c
reductase
in
addition
to
those
enzymes
involved
in
the
oxidation
of
testosterone.
On
October
23,
2001,
the
Mechanism
of
Toxicity
Assessment
Review
Committee
(MTARC)
reviewed
the
available
toxicology
data
submitted
in
support
of
a
proposed
threshold
mechanism
for
the
induction
of
thyroid
and
testicular
neoplasms
resulting
from
exposure
to
pronamide.
Although
the
results
of
these
special
endocrine
studies
conducted
by
the
Registrant
are
suggestive
of
a
pronamide
induced
thyroid
and
testicular
neoplastic
effect
via
disruption
of
the
pituitary
thyroid
and
pituitary
testis
hormonal
balance,
these
data
are
far
from
conclusive.
Based
on
the
Committee's
(MTARC)
evaluation
of
the
existing
pronamide
toxicology
data
base
(Memorandum:
M.
Centra,
January
21,
2001)
and
in
the
absence
of
any
additional
information,
it
was
determined
that
the
postulated
threshold
mechanism
for
the
induction
of
thyroid
and
testicular
neoplasms
is
not
supported
by
the
available
data.
Therefore,
HED
has
recommended
that
additional
studies
be
conducted
with
pronamide
to
determine
its
mechanism
of
endocrine
toxicity.
One
such
study,
a
comparative
assay
in
the
rat
that
is
designed
to
assess
thyroid
function
in
adult
animals
and
their
offspring
as
well
as
potential
central
nervous
system
effects
in
the
young,
is
required
by
the
Agency
because
of
the
endocrine
toxicities
observed
in
various
organ
systems
(thyroid
gland,
testes,
ovaries,
adrenal
glands,
pituitary
gland)
of
rats
and/
or
dogs.
The
Agency
is
required
under
the
Federal
Food,
Drug
and
Cosmetic
Act
(FFDCA),
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(including
all
pesticide
active
and
other
ingredients)
"may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(EDSTAC),
EPA
determined
that
there
was
scientific
bases
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(EDSP).
24
When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
pronamide
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.
4.0
EXPOSURE
ASSESSMENT
4.1
Summary
of
Registered
Uses
Pronamide
[3,5
dichloro
N(
1,1
dimethyl
2
propynyl)
benzamide],
or
propyzamide,
is
a
selective,
systemic,
pre
and
post
emergence
herbicide
registered
for
use
in
agricultural,
ornamental,
and
residential
settings.
There
are
two
manufacturers
of
pronamide
end
use
products
with
only
two
active
section
3
registrations.
There
are
also
nine
active
Section
24C
registrations.
Approximately
225,000
lb
of
active
ingredient
are
used
domestically
each
year.
Major
food/
feed
crops
include:
stone
fruits
(apricot,
cherry,
nectarine,
peach,
plum,
prune),
pome
fruits
(apple,
pear),
grapes,
artichokes,
berries
(blackberry,
blueberry,
boysenberry,
red
raspberry,
black
raspberry),
leafy
greens
(lettuce,
endive,
radicchio),
winter
peas,
chicory,
rhubarb,
sugarbeets,
and
forages
(alfalfa,
clover,
birdsfoot
trefoil,
crown
vetch,
sainfoin).
Non
agricultural
uses
include
woody
ornamentals,
ornamental
warm
season
grasses
grown
for
turf
(i.
e.
bermudagrass,
zoysiagrass,
St.
Augustine,
and
centipedegrass)
or
seed
(bermudagrass),
residential/
recreational
turf
(bermudagrass
lawns,
playing
fields,
and
golf
courses),
Christmas
trees,
grasses
grown
for
seed,
rangeland,
and
fallow
land.
In
terms
of
pounds
a.
i.,
total
usage
is
allocated
mainly
to
head
lettuce
(29%),
other
lettuce
(19%),
seed
crops
(13%),
fallowland
(11%),
hay
other
than
alfalfa
(8%),
horticulture
(3%)
and
alfalfa
(3%).
Rates
per
application
and
rates
per
year
are
each
generally
less
than
2
pounds
a.
i.
per
acre
for
agricultural
sites
(based
on
the
economic
analysis
by
A.
Holverson,
September
26,
2001).
Pronamide
label
rates
range
from
2
to
8
lbs
ai
per
acre
per
year
at
0.5
to
6
lbs
ai
per
acre
per
application,
with
from
one
to
four
applications
per
year.
Pronamide
is
formulated
as
a
wettable
powder
and
may
be
applied
by
ground
or
aerial
spray,
depending
on
the
crop.
States
with
significant
usage
in
terms
of
pounds
a.
i.
include
Arizona,
California,
Oregon
and
Washington.
Pre
harvest
intervals,
where
specified,
are
generally
long,
ranging
from
25
to
180
days.
There
are
several
active
Section
24C
state
labels.
For
risk
assessment
purposes
the
use
sites
and
use
patterns
on
these
24C
labels
are
covered
by
EPA
Reg.
No.
707
159.
4.2
Dietary
Exposure
and
Risk
Assessment
4.2.1
Residues
in
Food
Background
Pronamide/
propyzamide
[3,
5
dichloro
n(
1,1
dimethyl
2
propynyl)
benzamide]
tolerances
are
established
under
40
CFR
§180.317(
a),
(b),
and
(c).
The
tolerance
expression,
listed
in
(a)
and
(c),
is
in
terms
of
"the
combined
residues
of
the
herbicide
propyzamide
and
its
metabolites
(containing
the
3,5
dichlorobenzoyl
moiety
and
calculated
as
3,5
dichloro
N(
1,1
dimethyl
2
propynyl)
benzamide)."
The
25
tolerance
expression,
listed
in
(b),
is
in
terms
of
the
parent
only.
Pronamide
tolerances
listed
in
40
CFR
§180.317(
a)
range
from
0.02
ppm
(for
certain
animal
commodities)
to
10.0
ppm
(for
a
non
grass
animal
feeds
group).
The
time
limited
tolerances
listed
in
40
CFR
§180.317(
b),
with
an
expiration
date
of
12/
31/
01,
are
for
Section
18
emergency
exemptions
for
pronamide
uses
on
cranberries
(0.05
ppm)
and
grasses
(forage
1.0
ppm
and
hay
0.5
ppm).
The
tolerances
listed
in
40
CFR
§180.317(
c)
are
for
regional
registrations
of
pronamide
on
dried
(winter)
peas
(0.05
ppm)
and
rhubarb
(0.1
ppm).
Residue
Profile
The
qualitative
nature
of
the
residue
in
plants
is
adequately
understood.
The
4/
16/
93
Residue
Chapter
reported
that
studies
with
alfalfa
and
lettuce
indicate
that
pronamide
is
readily
absorbed
by
plants
through
the
root
system,
translocated
upward,
and
distributed
into
the
entire
plant.
The
degree
of
translocation
from
leaf
absorption
is
not
appreciable.
Metabolism
primarily
occurs
via
conjugation
to
(malonyl)
glucose.
No
evidence
of
fragmentation
or
loss
of
the
chloro
substituent
of
the
aromatic
ring
was
observed.
The
terminal
residues
of
concern
are
pronamide
and
its
metabolites
containing
the
3,5
dichlorobenzoyl
moiety.
For
purposes
of
reregistration,
no
additional
plant
metabolism
studies
are
required;
however,
because
the
available
metabolism
studies
were
only
conducted
on
alfalfa
and
lettuce,
the
Agency
may
require
additional
metabolism
studies
in
the
future
should
the
registrants
seek
for
additional
uses
on
other
crop
groups.
The
qualitative
nature
of
the
residue
in
animals
is
adequately
understood.
The
4/
16/
93
Residue
Chapter
reported
studies
involving
lactating
goats
and
laying
hens
indicate
that
the
primary
route
of
elimination
is
by
excretion
(urine
and
feces).
Minimal
residues
were
distributed
to
goat
and
poultry
muscle.
The
major
metabolites
in
the
eggs,
liver,
and
fat
of
poultry
are
pronamide
and
3,5
dichlorobenzoic
acid.
The
major
metabolites
in
the
milk,
fat,
muscle,
and
liver
of
goats
are
pronamide,
3,5
dichlorobenzoic
acid,
and
compounds
containing
the
3,5
dichlorobenzoyl
moiety.
The
metabolic
pathway
involves
modification
of
the
aliphatic
portion
of
pronamide.
The
terminal
residues
of
concern
are
pronamide
and
its
metabolites
containing
the
3,5
dichlorobenzoyl
moiety.
An
adequate
residue
analytical
method
is
available
for
plant
and
animal
tolerance
enforcement,
a
GLC/
ECD
method
listed
in
the
Pesticide
Analytical
Manual
(PAM)
Volume
II.
Designated
as
Method
I,
it
converts
residues
of
pronamide
and
its
metabolites
to
methyl
3,5
dichlorobenzoate.
The
data
collection
method
used
in
the
analysis
of
samples,
collected
from
a
recently
reviewed
field
rotational
crop
study,
was
a
GLC/
ECD
method
entitled
"An
Improved
Analytical
Method
for
the
Determination
of
Kerb
Residues
in
Crops
and
Soil."
The
method
was
adequately
validated
by
the
registrant
and
is
deemed
adequate
for
data
gathering
purposes.
This
method
should
be
validated
by
EPA
in
order
to
support
the
established
and
proposed
tolerances
for
pronamide.
Since
the
1993
dietary
chapter
was
published,
the
registrant
has
submitted
independent
laboratory
validation
for
a
revised
animal
method
(TR
34
91
68).
However,
prior
to
Agency
validation
of
Method
TR
34
91
68,
the
registrant
is
required
to
further
optimize/
improve
the
method
to
yield
acceptable
recoveries
at
higher
fortification
levels.
Then,
following
method
improvement,
the
registrant
is
required
to
submit
bridging
ILV
data.
Multiresidue
method
testing
data
for
pronamide
and
a
metabolite
containing
the
3,5
dichlorobenzoyl
moiety
are
also
available
(MRID434932
03);
these
data
have
been
forwarded
to
FDA.
26
Plant
product
residue
storage
stability
data
were
submitted
but
provided
only
indirect
evidence
that
the
precursors
to
the
3,5
dichlorobenzoyl
moiety,
are
most
likely
stable.
Additional
confirmatory
storage
stability
data
for
the
regulated
pronamide
metabolites
on
alfalfa,
apples,
grapes,
lettuce,
and
peaches
or
plums
are
required.
Likewise,
animal
product
storage
stability
data
were
submitted,
but
an
analysis
of
metabolites
containing
the
3,5
dichlorobenzoyl
moiety
was
not
included
in
the
study.
Additional
confirmatory
storage
stability
data
for
the
regulated
pronamide
metabolites
on
milk
are
required.
4.2.2
Acute
Dietary
Risk
from
Food
Sources
As
there
was
no
toxicological
endpoint
selected
for
acute
exposure,
an
acute
dietary
risk
assessment
was
not
performed.
4.2.3
Chronic
and
Cancer
Dietary
Risk
from
Food
Sources
A
refined
tier
3,
chronic
and
cancer
dietary
exposure
assessment
has
been
performed
for
pronamide.
The
analysis
is
based
primarily
upon
residue
monitoring
data
for
fruits
and
vegetables
from
the
U.
S.
Department
of
Agriculture
(USDA),
Agricultural
Marketing
Service's
Pesticide
Data
Program
(PDP)
and
FDA
data.
Tolerance
level
residues
were
used
for
four
registered
crops
(dried
peas,
endives,
radicchio,
and
cranberries),
and
anticipated
residues
were
calculated
for
meat,
milk,
poultry
and
eggs.
The
percent
crop
treated
(%
CT)
data
from
OPP's
Biological
and
Economic
Assessment
Division
(BEAD)
(September
26,
2001)
were
used
to
further
refine
the
dietary
exposure
assessment.
Pronamide
and
its
metabolites
containing
the
3,5
dichlorobenzoyl
moiety
are
the
residues
of
concern
and
should
be
included
in
the
assessment.
The
residues
measured
in
field
trials
include
the
other
metabolites
by
incorporation
of
a
hydrolysis
step.
However,
the
PDP
analyses
measured
only
the
parent
compound;
therefore,
the
method
limit
of
detection
(LOD)
was
used
instead
of
1/
2
the
LOD
to
account
for
metabolites
of
concern
for
the
treated
portion
of
those
crops.
No
processing
information
was
used
in
this
assessment.
DEEM™
default
processing
factors
were
used
wherever
they
existed
for
processed
food
derived
from
the
relevant
crops.
However,
because
residue
data
were
available
in
the
PDP
database
for
grape
juice,
pear
juice
and
apple
juice,
these
PDP
data
were
used
directly,
i.
e.
without
DEEM
default
processing
factors,
for
grape
juice
and
grape
wine,
and
for
pear
juice
and
apple
juice.
Factors
for
the
juice
concentrates
were
estimated
from
the
ratio
of
the
DEEM
default
factors
for
juice/
juice
concentrate.
The
dietary
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(DEEM™)
software
Version
7.75,
which
incorporates
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intake
by
Individuals
(CSFII),
1989
1992.
The
1989
92
data
are
based
on
the
reported
consumption
of
more
than
10,000
individuals
over
three
consecutive
days,
and
therefore
represent
more
than
30,000
unique
"person
days"
of
data.
Foods
"as
consumed"
(e.
g.,
apple
pie)
are
linked
to
raw
agricultural
commodities
and
their
food
forms
(e.
g.,
apples
cooked/
canned
or
wheat
flour)
by
recipe
translation
files
internal
to
the
DEEM
software.
HED
notes
that
there
is
a
degree
of
uncertainty
in
extrapolating
exposures
for
certain
population
subgroups
from
the
general
U.
S.
population
which
may
not
be
sufficiently
represented
in
the
consumption
surveys,
(e.
g.,
nursing
and
non
nursing
infants
or
Hispanic
females).
Therefore,
risks
estimated
for
these
population
subgroups
are
not
reported
explicitly
but
are
included
within
larger
27
representative
populations
having
sufficient
numbers
of
survey
respondents
(e.
g.,
all
infants
or
females,
13
50
years).
For
chronic
and
cancer
exposure
and
risk
assessment,
an
estimate
of
the
residue
level
in
each
food
or
food
form
(e.
g.,
orange
or
orange
juice)
on
the
commodity
residue
list
is
multiplied
by
the
average
daily
consumption
estimate
for
that
food/
food
form.
The
resulting
residue
consumption
estimate
for
each
food/
food
form
is
summed
with
the
residue
consumption
estimates
for
all
other
food/
food
forms
on
the
commodity
residue
list
to
arrive
at
the
total
estimated
exposure.
Exposure
estimates
are
expressed
in
mg/
kg
body
weight/
day
and
as
a
percent
of
the
cPAD.
This
procedure
is
performed
for
each
population
subgroup.
A
summary
of
the
pronamide
chronic
dietary
risk
estimates
are
shown
in
Table
4.
The
dietary
cancer
risk
estimates
are
shown
in
Table
5.
Table
4.
Results
of
Chronic
Dietary
Exposure
Analysis
Population
Subgroup
cPAD
1
(mg/
kg/
day)
Exposure
(mg/
kg/
day)
%
cPAD
U.
S.
Population
(total)
0.
03
mg/
kg/
day
0.
000004
<1%
All
Infants
(<
1
year)
0.
03
mg/
kg/
day
0.
000002
<1%
Children
1
6
years
0.
03
mg/
kg/
day
0.
000005
<1%
Children
7
12
years
0.
03
mg/
kg/
day
0.
000004
<1%
Females
13
50
0.03
mg/
kg/
day
0.
000004
<1%
Males
13
19
0.03
mg/
kg/
day
0.
000003
<1%
Males
20+
years
0.
03
mg/
kg/
day
0.
000004
<1%
Seniors
55+
0.03
mg/
kg/
day
0.
000005
<1%
cPAD
1
=
Chronic
PAD
=
Chronic
Population
Adjusted
Dose
=
0.03
mg/
kg/
day
Table
5.
Results
of
Dietary
Cancer
1
Exposure
Analysis
Population
Subgroup
Exposure
(mg/
kg/
day)
Cancer
Risk
Estimate
U.
S.
Population
(total)
0.
000004
1.06
X
10
7
1
Q1
*
=
0.0259
mg/
kg/
day
1
Because
the
estimated
exposure
is
well
below
the
chronic
and
cancer
levels
of
concern,
and
conservative
assumptions
were
used,
any
uncertainties
are
unlikely
to
cause
the
exposure
to
exceed
a
level
of
concern.
However,
there
are
some
conservative
assumptions
that
may
have
introduced
some
uncertainties
into
this
assessment.
Tolerance
level
residues
and
100
%
CT
was
used
for
endives,
dried
peas,
cranberries
and
radicchio.
The
LOD
was
used
instead
of
½LOD
for
the
non
detects
in
the
PDP
data.
For
the
animals
ARs
the
maximum
percent
crop
treated
was
assumed
instead
of
the
average
percent
crop
treated.
Default
DEEM
processing
factors
were
used
for
many
processed
foods.
28
4.3
Dietary
Exposure
from
Water
Sources
4.3.1.
Environmental
Fate
According
to
the
May
1994
Reregistration
Eligibility
Decision
for
pronamide,
results
from
environmental
fate
studies
indicate
that
pronamide
is
very
persistent
in
soil
and
water
with
half
lifes
of
many
months.
Pronamide
is
very
stable
in
water
and
photolytically
persistent
in
water
and
on
soil.
It
is
very
persistent
in
soil
under
aerobic
conditions,
with
an
estimated
half
life
of
13
months,
and
even
more
persistent
under
anaerobic
conditions.
Pronamide
is
persistent
but
relatively
mobile
in
soil.
Additionally,
rotational
crop
studies
show
accumulation
in
several
crop
types
at
one,
six
and
twelve
months
after
application.
For
these
reasons,
residues
of
pronamide,
per
se,
are
the
residues
of
concern
in
assessing
drinking
water
exposures.
4.3.2
Drinking
Water
Exposure
Estimates
Although
there
is
no
legal
requirement
under
the
Safe
Drinking
Water
Act
to
monitor
for
pronamide,
it
has
been
detected
in
surface
and
groundwater
in
various
locations
in
the
U.
S.
The
maximum
level
detected
was
0.365
ppb
(surface
water)
at
Zollner
Creek
near
Mt.
Abgel,
OR
on
Nov.
16,
1998
and
the
range
was
0.0037
to
0.365
(surface
water)
ppb
or
ug/
liter
(USGS
NAWQA
Data
Retrieval).
The
maximum
ground
water
detection
at
Benton
Ozark,
AK
was
0.82
ppb
on
April
13,
1994,
and
ranging
from
0.005
0.82
ppb
(ground
water).
A
Tier
I
Drinking
Water
Assessment
for
pronamide
was
calculated
(L.
Shanaman,
2001)
using
the
SCIGROW
model
for
groundwater
concentration
estimates.
The
Tier
I
groundwater
estimates
were
predicted
from
application
of
pronamide
at
maximum
label
rate
(2
lbs
active
ingredient
per
acre
four
times
per
year)
for
ornamental
herbaceous
plants,
and
represent
upper
bound
estimates
of
the
concentrations
that
might
be
found
in
groundwater
due
to
the
use
of
pronamide/
propyzamine.
The
resulting
modeled
groundwater
screening
concentration
is
3.0
ppb.
The
Tier
II
PRZM
EXAMS
model
(L.
Shanaman,
2002)
was
used
to
predict
EECs
for
pronamide
in
surface
water,
i.
e.,
90
th
percentile
average
annual
concentration
values
for
use
in
chronic
exposure
assessments,
and
36
year
mean
concentration
values
for
use
in
"cancer"
exposure
assessments.
Maximum
label
application
rates
were
used
for
major
use
crops.
Chronic
exposure
values
ranged
from
1.5
to
6.4
ppb,
and
cancer
average
exposure
values
ranged
from
0.535
to
4.3
ppb.
Conservative
inputs
were
used
for
the
environmental
(soil
and
water
metabolism)
assumptions,
i.
e.,
2
3x
uncertainty
factors
were
applied
to
soil
and
water
half
lives
used
in
the
PRZM
EXAMS
assessment.
4.4
Residential
Exposure
4.4.1
Residential/
Recreational
Postapplication
Exposure
and
Risk
Pronamide
is
a
restricted
use
herbicide,
so
the
public/
consumers
are
prohibited
from
handling
this
chemical.
Therefore
only
postapplication
exposures
were
assessed.
Earth
Care,
Division
of
United
Industries
Corp.,
(previously
Pursell
Industries)
has
requested
voluntary
cancellation
of
the
product
GREEN
UP
KERB
50W,
EPA
Reg.
No.
8660
85,
which
is
the
only
end
use
product
label
that
allows
professional
application
in
a
residential/
recreational
setting.
Pending
29
cancellation
of
this
use,
a
residential/
recreational
exposure
assessment
was
conducted.
The
agricultural
label
(EPA
Reg.
No.
707
159)
allows
one
application
per
year
to
grasses
grown
for
turf
for
sod
or
seed.
Based
on
the
application
rate,
timing,
and
residue
dissipation
data,
there
are
no
concerns
for
residential/
recreational
exposure
to
the
treated
turf
from
a
sod
farm.
This
label
No.
8660
85
indicates
a
maximum
application
rate
of
1.5
lb
ai/
acre
for
pre
emergence
applications
by
lawn
care
operators
(LCOs)
to
lawns,
playing
fields,
and
golf
courses
as
a
single
application.
The
maximum
application
rate
for
post
emergence
applications
is
1.0
lb
ai/
acre.
This
residential
label
does
not
specify
or
restrict
the
number
of
applications
allowed
per
year
to
turf.
Applications
to
turf
are
only
made
in
the
late
Fall
or
late
Winter.
For
residential
turf,
HED
assumed
one
application
per
year
to
estimate
short
term
exposures.
The
scenarios
assessed
for
the
purpose
of
determining
screening
level
risk
estimates
included
adults
and
children
(toddlers)
performing
high
contact
play
or
work
activities
on
treated
lawns,
and
adults
mowing
lawns
or
golfing
(see
Tables
6a,
6b,
and
6c)
.
Small
children
(toddlers)
were
also
assessed
for
incidental
oral
exposure
from
ingestion
of
soil,
object
to
mouth
activity
(turfgrass
mouthing),
and
hand
to
mouth
activity
while
playing
on
treated
lawns.
Some
of
these
exposures
were
combined,
where
it
was
deemed
reasonably
likely
that
activities
would
co
occur.
Residential
risk
estimates
utilized
data
from
a
submitted
turf
transferable
residue
(TTR)
study,
as
well
as
the
EPA's
original
and
revised
Draft
SOPs
for
Residential
Exposure
Assessment.
3,
5
For
pronamide
short
term
non
occupational
risks,
HED
has
established
a
level
of
concern
for
MOEs
<
300.
Results
from
a
recent
turf
transferable
residue
study
on
turf
using
pronamide
(i.
e.
MRID
44952501)
indicate
that
the
half
life
of
turf
transferrable
(TTR)
residues
was
slightly
less
than
two
days.
The
residential
label
(EPA
Reg.
No.
8660
85)
instructs
applicators
to
lightly
irrigate
within
a
day
of
application
if
no
rain
occurs.
Such
irrigation
occurred
at
24
hours
after
application
in
the
TTR
study.
Since
the
compound
is
soluble
in
water,
and
therefore
mobile,
it
is
likely
the
irrigation
dissolves
the
compound
and
transports
it
from
the
turf
into
the
soil.
Study
data
showed
that
residues
dissipate
to
below
the
level
of
quantification
by
day
14
following
application.
Therefore,
only
short
term
(i.
e.,
one
day
to
one
month)
exposures
would
be
anticipated,
since
most
of
the
pesticide
should
move
into
the
soil,
and
any
remaining
foliar
residues
should
dissipate
within
a
month.
While
residues
in
soil
could
persist
for
greater
than
30
days,
it
is
unlikely
that
children
will
play
on
or
contact
soil
for
greater
than
30
consecutive
days
during
the
winter
months.
Risk
estimates
based
on
residue
data
from
the
TTR
study
for
short
term
dermal
contact
with
treated
turf
during
high
contact
lawn
activities
on
day
zero
following
application
(DAT
0)
exceed
HED's
level
of
concern,
i.
e.
result
in
MOEs
<
300
for
adults
(MOE
=
71)
and
children
(MOE
=
42).
However,
using
DAT
2
residue
data
from
the
TTR
study
yielded
MOEs
that
do
not
exceed
the
level
of
concern
(MOEs
$
300)
for
adults
(MOE
=
890)
and
children
(MOE
=
530)
during
high
contact
lawn
activities.
Note
that
the
test
plots
were
irrigated
immediately
after
the
DAT
1
samples
were
taken,
i.
e.
24
hours
after
application
of
pronamide,
as
specified
on
the
label.
Using
DAT
2
residue
data
from
the
TTR
study
yielded
MOEs
that
do
not
exceed
the
level
of
concern
(MOEs
$
300)
for
adults
(MOE
=
890)
and
children
(MOE
=
530)
during
high
contact
lawn
activities.
The
data
show
that
thorough
watering
in
the
pronamide
product
clearly
alleviates
the
risk
concerns
for
dermal
exposure.
Risk
estimates
for
shortterm
dermal
contact
with
residues
on
treated
turf
during
the
low
contact
activities
of
grass
mowing
or
golfing
on
the
day
of
treatment
do
not
exceed
the
level
of
concern
(MOEs
$
300)
for
adults
(MOEs
2050
and
1025,
respectively).
30
Based
on
the
pesticide
label,
a
typical
residential/
recreational
lawn
application
rate
of
1.0
lb/
acre,
with
an
application
frequency
of
once
per
year,
was
assumed
for
the
residential
cancer
risk
assessment.
Pronamide
is
applied
in
the
dormant
season,
which
reduces
the
number
of
contact
days
expected.
A
single
exposure
is
deemed
more
likely,
but
up
to
14
days
exposure
could
occur
based
on
the
residue
dissipation
pattern.
The
14
day
average
turf
residues
from
the
TTR
study
(MRID
44952501)
were
used
(i.
e.
0.07913
µg/
cm
2
,
when
adjusted
to
a
typical
application
rate
of
1.0
lb
ai/
acre);
since
residues
in
the
TTR
study
dissipated
to
the
level
of
quantitation
by
14
days
after
application.
The
average
residue,
and
an
exposure
frequency
of
one
day
per
year,
or
50
days
in
a
lifetime,
was
assumed
for
high
contact
activities
(e.
g.
playing
and
working
on
lawns
and
turf)
and
low
contact
activities
(e.
g.
mowing
or
golfing).
An
adult
mowing
a
treated
lawn
one
day
each
year
has
a
cancer
risk
of
5.7
x
10
8
.
The
average
golfer
plays
18
times
per
year,
so
one
day's
exposure
is
possible
if
pronamide
is
applied
once
per
year
on
average.
The
adult
golfer
cancer
risk
is
estimated
at
1.2
x
10
7
.
An
adult
performing
dermal
high
contact
activities
on
turf
during
the
2
week
period
of
residue
dissipation
has
a
cancer
risk
of
8.4
x
10
7
.
The
HED
endeavors
to
reduce
estimated
cancer
risks
for
the
general
population
to
less
than
one
in
one
million
(10
6
).
In
order
to
exceed
the
cancer
risk
(1.0
x
10
6
),
exposure
frequencies
of
17.5,
8.7
and
1.2
days
per
year
would
be
needed
for
the
activities
of
mowing,
golfing
and
high
contact
work,
respectively.
Both
the
short
term
exposure
estimates
and
the
cancer
risk
estimate
relied
on
a
100%
dermal
absorption
factor,
which
results
in
a
high
end
dose
estimate.
The
short
term
dose
selection
from
a
developmental
study
is
based
on
a
weight
of
evidence
evaluation
of
the
entire
pronamide
database,
but
is
considered
protective
of
all
populations.
31
Table
6a:
Pronamide
Residential
Postapplication
Activities
on
Treated
Turf:
Dermal
Exposure
and
Non
Cancer
Risk
Estimates
Short
term
Risk
Estimates
at
DAT
0
using
TTR
Data
from
Turf
Study
Short
term
Risk
Estimates
at
DAT
2
using
TTR
Data
from
Turf
Study
Activity
Transfer
Coefficient
(cm
2
/hr)
(a)
TTR
µg/
cm
2
DAT
0
(b)
Dermal
Dose
(mg/
kg/
day)
(c)
MOE
(d)
TTR
µg/
cm
2
DAT
2
(b)
Dermal
Dose
(mg/
kg/
day)
(c)
MOE
(d)
high
contact
lawn
activities:
adults
14,500
0.2886
0.1196
71
0.023
0.00953
890
high
contact
lawn
activities:
toddler
5,200
0.2886
0.2001
42
0.023
0.0159
530
mowing
turf:
adults
500
0.2886
0.00413
2100
0.023
0.000329
26,000
golf
course
reentry:
adult
500
0.2886
0.00825
1000
0.023
0.000657
13,000
a
Transfer
coefficients
from
the
Residential
SOP's
(02/
01).
b
TTR
Source:
MRID
#
44952501
turf
transferable
residue
study
see
study
review
for
raw
data
and
regression
statistics.
Mean
observed
residue
values
from
DAT
0
through
DAT
0.5
were
used
for
the
DAT
0
short
term
assessments.
Mean
observed
residue
values
from
DAT
2
were
used
for
the
DAT
2
short
term
assessments.
c
Dermal
Dose
=
TTR
(µg/
cm
2
)
x
TC
(cm
2
/hr)
x
conversion
factor
(1
mg/
1,000
µg)
x
exposure
time
(2
hrs/
day
playing
&
mowing;
4
hrs
golfing)
x
Dermal
Absorption
Factor
(100%/
100)/
body
weight
(70
kg
adult
or
15
kg
child
1
6
yrs).
Short
term
MOEs
were
calculated
using
DAT
0
or
DAT
2
values.
d
MOE
=
NOAEL
(8.
46
mg/
kg/
day;
based
on
an
oral
study)
/
dermal
dose;
Note:
Target
MOE
is
300
or
greater;
numbers
are
rounded
to
two
significant
figures.
Note:
TTR
=
turf
transferable
residue
DAT
=
days
after
treatment
MOEs
in
bold
exceed
HEDs
level
of
concern
(i.
e.
MOEs
<
300).
32
Table
6b:
Pronamide
Postapplication
Dermal
Cancer
Risk
Estimates
for
Activities
on
Treated
Turf
Activity
Typical
Application
Rate
(lb
ai/
acre)
(a)
Days
of
Exposure
per
Year
(b)
14
day
avg
TTR,
adjusted
for
"typical"
rate
(µg/
cm
2
)
(c)
Transfer
Coefficient
(cm2/
hr)
(d)
Absorbed
Dermal
Daily
Dose
(mg/
kg/
day)
(e)
LADD
(mg/
kg/
day)
(f)
Cancer
Risk
(g)
Days
of
Exposure
per
Year
to
Exceed
1.0E
06
High
contact
activities
1.
0
1
0.
07913
7300
1.65E
02
3.
23E
05
8.
36E
07
1.
2
Mowing
1.0
1
0.07913
500
1.13E
03
2.
21E
06
5.
73E
08
17.5
Golfing
1.
0
1
0.
07913
500
2.26E
03
4.
42E
06
1.
15E
07
8.
7
a
Typical
(not
maximum)
application
rates
were
used
to
adjust
TTR
study
residue
data;
rate
confirmed
per
label
and
registrants'
comments.
b
Average
or
typical
days
per
year
for
cancer
risk
estimates,
based
upon
a
single
annual
application
and
a
fairly
rapid
foliar
dissipation
rate
(half
life
of
1.8
days,
from
TTR
study,
i.
e.
MRID
#
44952501).
c
TTR
source:
MRID
#
44952501
turf
transferable
residue
study
see
residential
exposure
assessment
for
raw
data
and
regression
statistics.
Mean
observed
residue
values
for
DAT
0
through
DAT
14
were
used
for
the
assessment.
The
study
was
conducted
in
NC
using
a
maximum
application
rate
of
1.5
lb
ai/
acre.
When
assessing
activities
involving
a
different
application
rate
than
what
was
used
in
the
study,
the
TTR
values
are
adjusted
proportionately
to
reflect
the
different
application
rate.
For
example,
for
the
"typical"
application
rate
of
1.0
lb
ai/
acre
:
normalized
(adjusted)
TTR
=
Turf
study
TTR
x
1.0
lb
ai/
A
assessed
rate
/
1.5
lb
ai/
A
study
rate;
0.1187
µg/
cm
2
x
1.0
lb
ai/
A
assessed
rate
/
1.5
lb
ai/
A
study
rate
=
0.07913
µg/
cm
2
.
d
Transfer
coefficient
from
the
updated
Residential
SOP's
(02/
01).
e
Absorbed
daily
dose
=
Average
day
0
14
TTR
(µg/
cm
2
)
x
intermediate
term
transfer
coefficient
(cm
2
/hr)
x
mg/
1,000
µg
x
exposure
duration
(2
hrs/
day
for
playing/
gardening/
mowing;
4
hrs/
day
to
play
golf)
x
dermal
absorption
factor
(100%)
/
body
weight
(70
kg
adult).
f
LADD
=
absorbed
daily
dose
(mg/
kg/
day)
x
days
of
exposure/
year
x
50
years
of
expected
exposure/
(365
days/
year
x
70
year
lifetime);
g
Cancer
Risk
=
LADD
x
Q
1
*
,
where
Q
1
*
=
2.59
x
10
2
(mg/
kg/
day)
1
TTR
used
for
cancer
risk
estimate
=
0
14
DAT
average
residue
normalized
for
typical
application
rate.
TTR
=
turf
transferable
residue
DAT
=
days
after
treatment
33
HED
also
assessed
short
term
risks
to
small
children
from
incidental
oral
ingestion
of
pronamide
residues
following
application
to
residential
lawns.
The
risk
calculations
for
small
children's
nondietary
ingestion
of
pronamide
on
treated
turf
indicate
that
risks
do
not
exceed
the
level
of
concern
(i.
e.
MOEs
$
300)
for
hand
to
mouth
(MOE
=
380),
incidental
ingestion
of
soil
(MOE
=
11,000),
and
incidental
object
to
mouth
(MOE
=
1500).
The
small
children's
combined
oral
hand
to
mouth
scenarios
(MOE
=
300)
also
do
not
exceed
the
level
of
concern.
When
risks
from
dermal
exposures
from
pronamide
to
small
children
are
combined
with
risks
from
incidental
oral
exposures,
the
combined
short
term
risk
estimates
exceed
the
level
of
concern
(MOEs
<
300),
with
an
MOE
at
37.
Note
that
the
high
contact
dermal
exposure
is
driving
the
overall
risk.
Also,
the
likelihood
of
all
of
the
assessed
incidental
oral
exposures
co
occuring
with
dermal
exposures
is
low.
Table
6c.
Residential
Oral
Nondietary
Short
term
Postapplication
Risks
to
Children
from
"Hand
to
Mouth"
and
Ingestion
Exposure
When
Reentering
Lawns
Treated
with
Pronamide
Type
of
Exposure
Short
term
Oral
Dose
a
(mg/
kg/
day)
Short
term
MOE
b
(1)
Hand
to
Mouth
Activity
0.0224
380
(2)
Incidental
Object
to
Mouth
(Turfgrass
Mouthing)
0.0056
1500
(3)
Incidental
Ingestion
of
Soil
7.51E
5
113,000
Combined
Oral
Nondietary
c
0.028
300
Combined
Oral
and
Dermal
d
37
a
Application
rate
for
the
short
term
estimates
represents
maximum
label
rate
from
current
EPA
registered
label:
EPA
Reg.
No.
8660
85
wettable
powder
product
formulation,
max
rate
is
1.5
lb
ai/
acre.
Incidental
oral
doses
were
calculated
using
formulas
presented
in
the
Residential
SOPs
(updated
1999
2000).
Short
term
doses
were
calculated
using
the
following
formulas:
(1)
Hand
to
mouth
oral
dose
to
children
on
the
day
of
treatment
(mg/
kg/
day)
=
[application
rate
(lb
ai/
acre)
x
fraction
of
residue
dislodgeable
from
potentially
wet
hands
(5%)
x
11.2
(conversion
factor
to
convert
lb
ai/
acre
to
µg/
cm
2
)]
x
median
surface
area
for
1
3
fingers
(20
cm
2
/event)
x
hand
to
mouth
rate
(20
events/
hour)
x
exposure
time
(2
hr/
day)
x
0.001
mg/
:
g]
x
50%
extraction
by
saliva
/
bw
(15
kg
child
1
6
yrs).
This
formula
is
based
on
proposed
changes
to
the
December
1999
Residential
SOPs.
(2)
Turf
mouthing
oral
dose
to
child
on
the
day
of
treatment
(mg/
kg/
day)
=
[application
rate
(lb
ai/
acre)
x
fraction
of
residue
dislodgeable
for
transfer
to
mouth
(20%)
x
11.2
(conversion
factor
to
convert
lb
ai/
acre
to
µg/
cm
2
)
x
ingestion
rate
of
grass
(25
cm
2
/day)
x
0.001
mg/
:
g]
/
bw
(15
kg
child
1
6
yrs).
(3)
Soil
ingestion
oral
dose
to
child
on
the
day
of
treatment
(mg/
kg/
day)
=
[(
application
rate
(lb
ai/
acre)
x
fraction
of
residue
retained
on
uppermost
1
cm
of
soil
(100%
or
1.0/
cm)
x
4.54e+
08
µg/
lb
conversion
factor
x
2.47e
08
acre/
cm
2
conversion
factor
x
0.67
cm
3
/g
soil
conversion
factor)
x
100
mg/
day
ingestion
rate
x
1.0e
06
g/
µg
conversion
factor]
/
bw
(15
kg;
child
1
6
yrs).
Short
term
dose
based
residue
on
the
soil
on
day
of
application.
b
Short
term
MOE
=
NOAEL
(8.46
mg/
kg/
day)
/
Oral
Dose
(mg/
kg/
day).
NOAEL
from
a
non
developmental
toxicity
study
in
rabbits;
target
MOE
of
100.
Numbers
are
rounded
to
two
significant
figures.
c
Combined
MOEs
=
NOAEL
/
[sum
of
incidental
oral
doses],
with
a
target
MOE
of
100.
d
Combined
Dermal
+
Incidental
Oral
MOEs
=
1/
[1/
MOEdermal
+
1/
MOEoral
];
see
Table
6a
for
dermal
MOE
for
high
contact
short
term
activity
for
toddlers
on
turf
(MOE
=
42).
MOEs
in
bold
exceed
HEDs
level
of
concern
(i.
e.
MOEs
<
300).
The
exposure
estimates
generated
for
the
residential/
recreational
turf
uses
used
the
HED
SOPs
that
are
based
on
some
upper
percentile
assumptions
(i.
e.,
duration
of
exposure
and
maximum
application
rate
for
short
term
assessments)
and
are
considered
to
be
representative
of
high
end
exposures.
The
34
uncertainties
associated
with
this
assessment
stem
from
the
use
of
assumptions
regarding
the
transfer
of
pronamide
residues.
The
exposure
estimates
are
believed
to
be
reasonably
high
end
estimates,
since
the
maximum
application
rate
is
used,
a
100%
dermal
absorption
factor
is
assumed,
and
exposures
are
assumed
to
occur
on
the
day
of
treatment.
4.4.2
Spray
Drift
Spray
drift
is
always
a
potential
source
of
exposure
to
residents
nearby
to
spraying
operations.
This
is
particularly
the
case
with
aerial
application,
but,
to
a
lesser
extent,
could
also
be
a
potential
source
of
exposure
from
groundboom
application
methods.
The
Agency
has
been
working
with
the
Spray
Drift
Task
Force,
EPA
Regional
Offices
and
State
Lead
Agencies
for
pesticide
regulation
and
other
parties
to
develop
the
best
spray
drift
management
practices.
The
Agency
is
now
requiring
interim
mitigation
measures
for
aerial
applications
that
must
be
placed
on
product
labels/
labeling.
The
Agency
has
completed
its
evaluation
of
the
new
data
base
submitted
by
the
Spray
Drift
Task
Force,
a
membership
of
U.
S.
pesticide
registrants,
and
is
developing
a
policy
on
how
to
appropriately
apply
the
data
and
the
AgDRIFT
computer
model
to
its
risk
assessments
for
pesticides
applied
by
air,
orchard
airblast
and
ground
hydraulic
methods.
After
the
policy
is
in
place,
the
Agency
may
impose
further
refinements
in
spray
drift
management
practices
to
reduce
off
target
drift
and
risks
associated
with
aerial
as
well
as
other
application
types
where
appropriate.
5.0
AGGREGATE
RISK
ASSESSMENT
AND
RISK
CHARACTERIZATION
FQPA
requires
an
aggregate
risk
assessment
to
be
conducted
considering
all
non
occupational
sources,
including
exposure
from
water,
food,
and
residential
use.
Because
there
are
potential
exposures
to
treated
turf,
the
aggregate
exposure
assessment
for
pronamide
includes
exposure
estimates
from
residential
sources
as
well
as
food
and
drinking
water.
HED
has
calculated
drinking
water
levels
of
comparison
(DWLOCs)
for
chronic
exposure
to
pronamide
in
surface
and
groundwater
which
are
presented
in
Tables
7a,
7b
and
7c.
DWLOCs
were
calculated
using
default
body
weights
and
drinking
water
consumption
figures.
Assumptions
used
in
calculating
the
DWLOCs
include
70
kg
body
weight
for
the
U.
S.
population,
60
kg
body
weight
for
adult
females,
10
kg
body
weight
for
children,
two
liters
of
water
consumption
per
day
for
adults,
and
one
liter
consumption
for
children.
Generally,
risks
from
drinking
water
are
assessed
by
comparing
the
DWLOCs
to
the
estimated
environmental
concentrations
(EECs)
in
surface
water
and
groundwater.
In
the
case
of
pronamide,
there
are
monitoring
data
available
for
surface
and
ground
water.
The
monitoring
database
used
in
the
risk
assessment
is
considered
to
be
of
good
quality
(USGS),
but
the
data
are
not
from
sampling
specifically
targeted
for
pronamide
use
areas.
These
data
have
been
compared
to
the
model
results
to
characterize
the
Tier
I
and
Tier
II
estimates
for
the
groundwater
and
surface
water,
respectively.
As
can
be
seen
from
that
comparison,
the
monitoring
data
are
typically
at
least
10
fold
lower
than
the
model
estimates.
The
USGS
monitoring
data
are
also
lower
than
the
short
term
and
chronic
DWLOC.
However,
the
model
estimates
for
Northwest
pears
and
apples,
and
alfalfa
grown
in
CA
indicate
that
an
extreme
case
using
highest
label
rates
might
present
a
concern
for
cancer.
Typical
rates
for
the
fruit
are
one
half
,
and
alfalfa
is
one
quarter
the
rates
used
in
the
model,
according
to
the
latest
QUA
report.
The
model
estimates
would
therefore
be
decreased
proportionately
for
those
crops
if
pronamide
were
applied
35
at
the
lower
or
more
typical
use
rate.
See
Tables
7a,
7b,
7c.
5.1
Acute
Risk
Acute
aggregate
risk
was
not
estimated
as
no
acute
toxicological
endpoints
were
identified
for
pronamide.
5.2
Short
Term
Risk
5.2.1
Aggregate
Short
Term
Risk
Assessment
Because
the
short
term
dermal
postapplication
exposure
estimates
for
children
exceeded
the
level
of
concern,
an
aggregate
exposure
estimate
combining
dermal
exposure
with
food
and
drinking
water
intake
was
not
conducted
for
that
population.
Adults
engaged
in
high
contact
activities
on
newly
treated
turf
also
had
dermal
exposures
which
exceeded
the
level
of
concern.
However,
an
aggregate
short
term
exposure
assessment
was
conducted
for
the
low
contact
adult
golfing
exposure
scenario.
This
shortterm
risk
estimate
may
be
useful
in
risk
management
decisions.
The
short
term
aggregate
exposure
estimate
which
included
the
golfer
dermal
exposure
did
not
exceed
the
level
of
concern
(golfer
MOE
=
1000)
.
5.2.2
Short
Term
DWLOC
Calculations
Since
the
drinking
water
calculations
were
based
on
modeling
estimates,
Drinking
Water
Levels
of
Comparison
(DWLOCs)
were
calculated
for
short
term
exposure.
The
DWLOC
is
the
concentration
of
a
chemical
in
drinking
water
that
would
be
acceptable
as
an
upper
limit
in
light
of
total
aggregate
exposure
to
that
chemical
from
food,
water,
and
(for
short
term
estimate)
non
occupational
(residential)
sources.
Comparisons
are
made
between
DWLOCs
and
the
estimated
concentrations
of
pronamide
in
surface
water
and
ground
water
generated
via
PRZM/
EXAMS
and
SCI
GROW,
respectively.
If
the
model
estimate
is
less
than
the
DWLOC,
there
is
generally
no
drinking
water
concern.
Monitoring
data
for
pronamide
in
surface
water
had
a
maximum
value
from
all
samples
and
all
years
of
0.365
ppb,
and
0.82
ppb
for
groundwater.
Monitoring
data
ranged
from
0.0037
to
0.365
ppb
in
surface
water,
and
from
0.82
0.005
ppb
in
ground
water.
Results
showed
that
for
low
contact
adult
activities,
such
as,
mowing
and
golfing,
modeled
and
measured
concentrations
of
pronamide
are
considerably
less
than
the
DWLOCs
(range
560
700
ppb)
for
all
populations.
Consequently,
for
these
adult,
low
contact
activities,
there
is
no
short
term
concern
for
drinking
water
from
surface
or
groundwater
sources.
However,
as
noted
above,
short
term
postapplication
dermal/
incidental
oral
exposures
of
children
to
pronamide
on
lawns
after
application
result
in
risk
estimates
that
exceed
HED's
levels
of
concern.
Aggregating
children's
exposures
through
food,
water,
and
residential
uses
results
in
risk
estimates
that
further
exceed
levels
of
concern.
36
Table
7a.
Short
Term
Aggregate
Risk
and
DWLOC
Calculations
for
Adult
Low
Contact
Activities
only
Population
Short
Term
Scenario
NOAEL
mg/
kg/
day
Target
MOE
1
Max
Exposure
2
mg/
kg/
day
Average
Food
Exposure
mg/
kg/
day
Residential
Exposure
3
mg/
kg/
day
Aggregate
MOE
(food
and
residential)
4
Max
Water
Exposure
5
mg/
kg/
day
Ground
Water
EEC
6
(µg/
L)
Surface
Water
EEC
6
(µg/
L)
Short
Term
DWLOC
7
(µg/
L)
Adult
Male
8
8.46
300
0.0282
4
e
06
0.00825
1000
0.020
3
1.
6
6.5
700
Adult
Female
4
e
06
0.0096
880
0.0186
560
Child
5
e
06
0.20
9
NA
9
0
0
Highest
Exposed
Adult
Subpop
10
5
e
06
0.0096
880
0.0186
560
1
Based
on
10x
uncertainty
for
interspecies
and
10x
for
intraspecies
variation
and
3x
for
FQPA
for
endocrine
effects;
body
weights
used
are
70kg
male,
60
kg
female,
10
kg
child)
2
Maximum
Exposure
(mg/
kg/
day)
=
NOAEL/
Target
MOE
3
Residential
Exposure
=
[Oral
exposure
+
Dermal
exposure
+
Inhalation
Exposure]
4
Aggregate
MOE
=
[NOAEL
÷
(Avg
Food
Exposure
+
Residential
Exposure)]
5
Maximum
Water
Exposure
(mg/
kg/
day)
=
Target
Maxium
Exposure
(Food
Exposure
+
Residential
Exposure)
6
The
crop
producing
the
highest
level
was
used.
7
DWLOC(
µg/
L)
=
[maximum
water
exposure
(mg/
kg/
day)
x
body
weight
(kg)]
;
where
male
bw
=
70
kg;
female
bw=
60
kg;
child
1
7
bw
=
10
kg;
[water
consumption
(L)
x
10
3
mg/
µg]
water
consumption
2
L/
day
(adults);
1
L/
day
(
infants
and
children)
8
While
the
high
contact
dermal
exposure
estimate
alone
exceeds
the
level
of
concern,
the
lower
contact
exposure
from
golfing
does
not
and
was
aggregated
to
illustrate
the
total
risk
for
this
non
residential,
recreational
use
scenario
9
NA
=
doses
not
aggregated,
as
the
small
child
estimated
hand
mouth
incidental
oral
exposure
alone
exceeds
the
level
of
concern
10
Exposure
refers
to
the
highest
dietary
exposure,
in
this
case
for
female
seniors.
5.3
Intermediate
Term
Risk
Based
on
the
label
use
pattern,
including
seasonal
applications,
and
residue
dissipation
on
turf
in
14
days,
no
intermediate
or
long
term
residential
non
dietary
exposures
to
pronamide
are
anticipated.
An
intermediate
term
risk
assessment
was
not
conducted
as
there
were
no
exposures
of
applicable
(30
days
to
six
months)
duration.
5.4
Chronic
Risk
37
5.4.1
Chronic
Aggregate
Risk
Assessment
Due
to
the
short
term,
intermittent
nature
of
residential
or
recreational
exposure
to
pronamide,
only
dietary
and
water
intake
were
included
in
the
chronic
aggregate
exposure
estimate.
The
DWLOC
chronic
is
the
concentration
in
drinking
water
as
a
part
of
the
aggregate
chronic
exposure
that
occupies
no
more
than
100%
of
the
chronic
PAD
when
considered
together
with
other
sources
of
exposure.
To
calculate
the
DWLOC
for
chronic
exposure
relative
to
a
chronic
toxicity
endpoint,
the
chronic
dietary
food
exposure
(from
DEEM™)
was
subtracted
from
the
chronic
PAD
to
obtain
the
acceptable
chronic
exposure
to
pronamide
in
drinking
water.
The
DWLOC
was
calculated
and
compared
to
the
EECs.
The
EECs
for
average
concentrations
of
pronamide
were
based
on
PRZM
EXAMS
for
surface
water
and
SCI
GROW
for
groundwater.
The
chronic
DWLOCs
(300
1050
ug/
L)
were
greater
than
the
EECs
for
modeled
surface
water
(1.6
6.5
ug/
L),
and
modeled
groundwater
(3
ug/
L).
In
addition,
non
targeted
USGS
monitoring
data
ranged
from
0.0037
to
0.365
ppb
in
surface
water,
and
from
0.005
0.82
ppb
in
ground
water.
HED
concludes
the
chronic
aggregate
risk
estimates
do
not
exceed
the
level
of
concern.
5.4.2
Chronic
DWLOC
Calculations
Table
7b.
Pronamide
Summary
of
Chronic
DWLOC
Calculations
Population
Subgroup
cPAD
(mg/
kg/
day)
Food
Exposure
(mg/
kg/
day)
Available
Water
Exposure
(mg/
kg/
day)
Chronic
DWLOC
(µg/
L)
EFED
Generated
EECs
1
USGS
SW
/
GW
Monitoring
6
(µg/
L)
Ground
Water
SCI
GROW)
(µg/
L)
PRZM
EXAMS
Chronic
(µg/
L)
U.
S.
Population
a
0.03
4
e
06
0.03
1050
3
1.6
6.5
SW:
0.0037
0.365
GW:
0.005
0.82
Females
13
50
yrs
b
4
e
06
900
Children
1
6
yrs
25
e
06
300
All
Infants
2
e
06
300
Chronic
aggregate
exposures
represent
only
dietary
and
water
consumption;
no
chronic
non
dietary
exposures
anticipated
1
EEC
=
Estimated
Environmental
Concentrations
2
Pronamide
surface
water
EECs
are
from
FIRST
modeling
.
DWLOC
=
water
exposure
X
body
weight
(where
water
exposure
=
cPAD
food
exposure)
Liters
of
water
X
10
3
Body
weight
=
70
kg
for
U.
S.
Population,
60
kg
for
females,
10
kg
for
infants
and
children
Consumption
=
2L/
day
for
Adults
and
1L/
day
for
infants
and
children
5
USGS
NAWQA
Data
Retrieval;
Maximum
ground
water
detection
at
Benton
Ozark,
AK
at
0.82
ppb
on
April
13,
1994,
data
ranging
form
0.82
0.005
ppb
(ground
38
water).
5.5
Cancer
Risk
Estimates
5.5.1
Cancer
Aggregate
Risk
Assessment
The
estimated
cancer
risk
from
one
day
per
year
of
postapplication
(high
or
low
contact)
exposure
to
average
pronamide
residues
on
treated
turf
did
not
exceed
the
Agency's
level
of
concern
of
1.0
x
10
6
(one
in
a
million).
High
contact
activities
for
more
than
one
day
would
exceed
the
level
of
concern.
Based
on
the
seasonal
use
pattern,
only
one
to
several
days
postapplication
exposure
are
considered
likely,
and
it
is
unlikely
that
a
single
person
would
have
have
daily
high
contact
exposure
during
the
14
day
dissipation
period.
The
use
of
a
100
%
dermal
absorption
factor
adds
to
the
conservatism
of
the
cancer
risk
estimate.
For
average
dietary
consumption,
the
dose
did
not
result
in
a
cancer
risk
estimate
of
concern.
Therefore
the
cancer
estimates
from
each
route
can
be
aggregated.
5.5.2
Cancer
DWLOC
Calculations
The
estimated
DWLOC
for
cancer
from
food,
drinking
water,
and
residential
exposure
is
<0.1
ppb.
The
Tier
2
PRZM/
EXAMS
37
year
mean
concentration
estimates
range
from
less
than
1
ppb
to
4.3
ppb.
The
available
USGS
surface
and
groundwater
monitoring
data
ranged
from
0.0037
to
0.365
ppb
in
surface
water,
and
from
0.82
0.005
ppb
in
ground
water.
Further
refinement
of
the
drinking
water
modeling
estimates
and/
or
detailed
analysis
of
water
monitoring
data
might
be
useful
for
risk
assessment
and
risk
management
decisions,
once
the
final
disposition
of
residential/
recreational
uses
is
known..
39
Table
7c.
Cancer
DWLOC
Calculations
USGS
SW
/
GW
Monitoring
6
(µg/
L)
Population
Target
Max
Exposure
2
mg/
kg/
day
Chronic
Food
Exposure
mg/
kg/
day
Residential
Exposure
(LADD)
mg/
kg/
day
Aggregate
cancer
risk
(food
and
residential)
Max
Water
Exposure
3
mg/
kg/
day
Cancer
DWLOC
5
(µg/
L)
Ground
Water
EEC
4
(µg/
L)
PRZM
EXAMS
Cancer
(µg/
L)
U.
S.
Pop
3.
86
e
05
4
e
06
3.2
e
05
9.3
e
07
2.6
e
06
<0.1
3
0.
535
4.35
SW:
0.0037
0.365
GW:
0.005
0.82
1
EPA's
goal
is
to
mitigate
cancer
risk
to
1
x
10
6
.
2
Target
Maximum
Exposure
(mg/
kg/
day)
=
[negligible
risk/
Q*]
;
negligible
risk
=
1.0
e
06;
Q
1
*
=
0.0259
3
Maximum
Water
Exposure
(mg/
kg/
day)
=
[Target
Maximum
Exposure
(Chronic
Food
Exposure
+
Residential
Exposure
(Lifetime
Average
Daily
Dose))]
4
The
crop
producing
the
highest
level
was
used.
5
Cancer
DWLOC(
µg/
L)
=
[maximum
water
exposure
(mg/
kg/
day)
x
body
weight
(kg)]
[water
consumption
(L)
x
10
3
mg/
µg]
2
Body
weight
=
70
kg
for
U.
S.
Population
Consumption
=
2L/
day
for
Adults
and
1L/
day
for
infants
and
children
6
USGS
NAWQA
Data
Retrieval;
Maximum
ground
water
detection
at
Benton
Ozark,
AK
at
0.82
ppb
on
April
13,
1994,
data
ranging
form
0.82
0.005
ppb
(ground
water).
The
estimated
cancer
risk
from
one
day
per
year
of
postapplication
(high
or
low
contact)
exposure
to
pronamide
treated
turf
did
not
exceed
the
Agency's
level
of
concern
of
1.0
x
10
6
(one
in
a
million).
However,
more
than
one
day's
exposure
to
treated
turf
while
golfing
could
result
in
a
cancer
risk
estimate
greater
than
1.0
x
10
6
.
For
average
dietary
consumption,
the
dose
did
not
result
in
a
cancer
risk
estimate
of
concern.
However,
when
the
golfing
exposure
is
added
to
the
chronic
food
exposure,
the
estimated
DWLOC
for
cancer
is
<0.1
ppb,
which
is
below
most
of
the
screening
level
drinking
water
concentrations
estimated
by
EFED,
and
therefore
exceeds
the
level
of
concern.
Some
of
the
surface
and
groundwater
monitoring
data
are
greater
than
the
DWLOC,
which
generates
a
concern
for
cancer.
Therefore,
HED
has
some
concerns
for
exposures
to
pronamide
in
drinking
water
for
cancer
risk.
The
model
estimates
for
Northwest
pears
and
apples,
and
alfalfa
grown
in
CA
indicate
that
an
extreme
case
using
highest
label
rates
might
present
a
concern
for
cancer.
Typical
rates
for
the
fruit
are
one
half
,
and
alfalfa
is
one
quarter
the
rates
used
in
the
model,
according
to
the
latest
QUA
report.
The
model
estimates
40
would
therefore
be
decreased
proportionately
for
those
crops
if
pronamide
were
applied
at
the
lower
or
more
typical
use
rate.
The
registrant
for
pronamide
has
requested
cancellation
of
the
turf
use
in
a
letter
dated
January
14,
2002.
If
the
turf
use
is
canceled,
there
will
be
no
residential
or
recreational
non
dietary
exposures,
and
the
only
remaining
risk
of
concern
will
be
the
aggregate
food
and
drinking
water
cancer
estimate.
Without
residential/
recreational
exposure,
the
cancer
DWLOC
will
be
1.2
ppb.
Additional
monitoring
data,
targeted
at
water
sources
near
pronamide
high
use
sites,
such
as
lettuce
fields
in
Monterey
County,
CA,
could
help
refine
the
cancer
risk
assessment.
Uncertainties
Aggregate
risk
estimates
as
conducted
in
this
document
are
considered
to
be
high
end
or
conservative
estimates,
and
can
generally
be
refined,
if
necessary,
with
chemical
specific
data.
The
postapplication
dermal
risk
estimates
were
based
on
the
Office
of
Pesticide's
Residential
SOPs
(1997,
2001),
which
utilize
both
central
tendency
and
upper
percentile
assumptions
(i.
e.,
duration
of
exposure
and
maximum
application
rate
for
short
term
assessments)
and
are
considered
to
be
representative
of
high
end
exposures.
The
adult
and
children's
transfer
coefficients
are
based
on
the
Jazzercise
protocol
and
an
upper
percentile
exposure
duration
value.
Where
study
data
were
used
with
the
SOP
formulae,
these
risk
estimates
were
better
refined,
and
hence,
less
conservative.
Therefore,
the
exposure
estimates
related
to
turf
skin
contact
(which
were
based
on
study
data)
are
more
refined
than
the
estimates
of
incidental
ingestion
In
addition,
dermal
doses
assumed
a
100%
dermal
absorption
factor,
and
exposures
are
assumed
to
occur
on
the
day
of
treatment
(highest
residue).
6.0
CUMULATIVE
EXPOSURE
TO
SUBSTANCES
WITH
A
COMMON
MECHANISM
OF
TOXICITY
The
Food
Quality
Protection
Act
(1996)
stipulates
that
when
determining
the
safety
of
a
pesticide
chemical,
EPA
shall
base
its
assessment
of
the
risk
posed
by
the
chemical
on,
among
other
things,
available
information
concerning
the
cumulative
effects
to
human
health
that
may
result
from
dietary,
residential,
or
other
non
occupational
exposure
to
other
substances
that
have
a
common
mechanism
of
toxicity.
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
A
person
exposed
to
a
pesticide
at
a
level
that
is
considered
safe
may
in
fact
experience
harm
if
that
person
is
also
exposed
to
other
substances
that
cause
a
common
toxic
effect
by
a
mechanism
common
with
that
of
the
subject
pesticide,
even
if
the
individual
exposure
levels
to
the
other
substances
are
also
considered
safe.
HED
did
not
perform
a
cumulative
risk
assessment
as
part
of
this
risk
assessment
for
pronamide
because
HED
has
not
yet
initiated
a
review
to
determine
if
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
pronamide.
For
purposes
of
this
tolerance
reassessment
review,
EPA
has
assumed
that
pronamide
does
not
have
a
common
mechanism
of
toxicity
with
other
substances.
41
7.0
INCIDENT
DATA
A
review
of
incident
data
sources
found
that
relatively
few
incidents
of
pronamide
poisonings
were
reported
(J.
Blondell,
M.
Spann,
August
10,
2001).
There
are
only
two
Poison
Center
reports,
no
incident
reports
in
OPPs
Incident
Data
System
and
only
two
reports
from
the
California
Pesticide
Illness
Surveillance
Program.
On
the
list
of
the
top
200
chemicals
for
which
National
Pesticide
Telecommunications
Network
(NPTN)
received
calls
from
1984
1991
inclusively,
pronamide
was
not
reported
to
be
involved
in
human
incidents.
8.0
TOLERANCE
REASSESSMENT
RECOMMENDATIONS
8.1
Tolerance
Reassessment
Recommendation
Pronamide
tolerances
are
established
under
40
CFR
§180.317(
a),
(b),
and
(c).
The
tolerance
expression,
listed
in
(a)
and
(c),
is
in
terms
of
the
combined
residues
of
the
herbicide
propyzamide
and
its
metabolites
(containing
the
3,5
dichlorobenzoyl
moiety
and
calculated
as
3,5
dichloro
N(
1,1
dimethyl2
propynyl)
benzamide).
The
tolerance
expression,
listed
in
(b),
is
in
terms
of
the
parent
only.
HED
recommends
that
the
tolerance
expression
under
(b)
be
modified
to
include
the
metabolites
(containing
the
3,5
dichlorobenzoyl
moiety
and
calculated
as
3,5
dichloro
N(
1,1
dimethyl
2
propynyl)
benzamide).
A
summary
of
pronamide
tolerance
reassessments
is
presented
in
Table
8.
For
a
full
discussion
of
tolerances
see
the
HED
Residue
Chemistry
Chapter
(J.
Morales,
February
28).
Tolerances
for
inadvertent
residues
of
pronamide
and
its
metabolites
containing
the
3,5
dichlorobenzoyl
moiety
should
be
proposed
for:
(1)
the
forage
of
cereal
grains
crop
at
0.6
ppm;
(2)
the
straw
of
cereal
grains
crop
at
0.3
ppm;
and
(3)
the
hay
of
cereal
grains
crop
at
0.2
ppm.
The
required
tolerance
proposal
is
concomitant
with
a
recommendation
for
a
label
revision
to
establish
a
180
day
plantback
interval
for
Crop
Group
16.
.
Table
8.
Tolerance
Reassessment
Summary
for
Pronamide
Commodity
Established
Tolerance
(ppm)
Reassessed
Tolerance
(ppm)
Comment
Correct
Commodity
Definition
Tolerances
Listed
Under
40
CFR
§180.317(
a)
Apples
0.1
0.
1
Apple
Artichokes
0.
1
0.051
Artichoke
Blackberries
0.05
0.05
Blackberry
Blueberries
0.05
0.05
Blueberry
Boysenberries
0.05
0.05
Boysenberry
Cattle,
fat
0.
02
0.
20
Cattle,
kidney
0.
4
0.4
Cattle,
liver
0.4
0.
4
Cattle,
mbyp
(except
kidney,
liver)
0.02
0.02
Cattle,
meat
0.02
0.02
Eggs
0.02
0.02
Table
8.
Tolerance
Reassessment
Summary
for
Pronamide
Commodity
Established
Tolerance
(ppm)
Reassessed
Tolerance
(ppm)
Comment
Correct
Commodity
Definition
42
Endive
(escarole)
1.0
1.
0
Goats,
fat
0.
02
0.
20
Goats,
kidney
0.
4
0.4
Goats,
liver
0.4
0.
4
Goats,
mbyp
(except
kidney,
liver)
0.02
0.02
Goats,
meat
0.02
0.02
Grapes
0.1
0.
1
Grape
Hogs,
fat
0.
02
0.
20
Hogs,
kidney
0.
4
0.4
Hogs,
liver
0.4
0.
4
Hogs,
mbyp
(except
kidney,
liver)
0.02
0.02
Hogs,
meat
0.02
0.02
Horses,
fat
0.
02
0.
20
Horses,
kidney
0.
4
0.4
Horses,
liver
0.4
0.
4
Horses,
mbyp
(except
kidney,
liver)
0.02
0.02
Horses,
meat
0.02
0.02
Lettuce
1.0
1.
0
Lettuce,
head
Only
head
lettuce
is
supported
by
acceptable
data;
leaf
lettuce
uses
must
be
removed
from
the
label.
Alternatively,
the
label
may
be
revised
to
specify
a
practical
PHI
(35
day)
for
leaf
lettuce
and
supporting
data
be
submitted.
Milk
0.02
0.02
Nongrass
animal
feeds
10.0
10.0
Nongrass
animal
feeds
(forage,
fodder,
straw,
and
hay)
group
Pears
0.
1
0.1
Pear
Poultry,
fat
0.
02
0.
02
Poultry,
kidney
0.
2
Revoke
Tolerances
are
typically
not
established
for
poultry
kidneys.
Poultry,
liver
0.2
0.
2
Poultry,
mbyp
(except
kidney,
liver)
0.02
0.02
Poultry,
mbyp
(except
liver)
Poultry,
meat
0.02
0.02
Radicchio,
greens
(tops)
2.
0
2.0
Raspberries
0.05
0.05
Raspberry
Sheep,
fat
0.
02
0.
20
Sheep,
kidney
0.
4
0.4
Sheep,
liver
0.4
0.
4
Table
8.
Tolerance
Reassessment
Summary
for
Pronamide
Commodity
Established
Tolerance
(ppm)
Reassessed
Tolerance
(ppm)
Comment
Correct
Commodity
Definition
43
Sheep,
mbyp
(except
kidney,
liver)
0.02
0.02
Sheep,
meat
0.02
0.02
Stone
fruits
0.1
0.
1
Stone
fruits
group
Tolerances
To
Be
Proposed
Under
40
CFR
§180.317(
a)
Alfalfa,
seed
10.0
Tolerance
recommendation
is
contingent
upon
required
label
revision
to
specify
a
50
day
PHI
and
a
maximum
seasonal
rate
of
2.0
lb
ai/
A.
Tolerances
Listed
Under
40
CFR
§180.317(
b)
Cranberries
0.05
[with
12/
31/
01
expiration
date]
0.05
Cranberry
Grass,
forage
1.0
[with
12/
31/
01
expiration
date]
1.0
Additional
data
are
required
for
the
establishment
of
permanent
tolerances
on
grass
forage
and
hay.
Grass,
hay
0.5
[with
12/
31/
01
expiration
date]
0.5
Tolerances
Listed
Under
40
CFR
§180.317(
c)
Peas,
dried
(winter)
0.05
TBD
Pea,
field,
seed
Rhubarb
0.1
0.
1
Tolerances
To
Be
Proposed
Under
40
CFR
§180.317(
c)
Pea,
field,
hay
TBD
Pea,
field,
vines
–
TBD
CODEX
HARMONIZATION
No
Codex
MRLs
have
been
established
or
proposed
for
residues
of
pronamide.
Therefore,
issues
of
compatibility
with
respect
to
U.
S.
tolerances
and
Codex
MRLs
do
not
exist.
9.0
DATA
NEEDS
Product
Chemistry
Most
pertinent
product
chemistry
data
requirements
are
satisfied
for
the
Rohm
and
Haas
94.6%
T/
TGAI,
except
additional
data
are
required
concerning
the
materials
used
to
produce
the
product
and
UV/
Visible
absorption
(OPPTS
830.1600
and
7050).
Additional
data
are
also
required
for
the
Rohm
and
Haas
51%
FI
concerning
oxidation/
reduction,
explodability,
storage
stability,
and
corrosion
characteristics
(OPPTS
830.6314,
6316,
6317,
and
6320).
Provided
that
the
registrant
submits
the
data
required
in
the
attached
data
summary
tables
for
the
pronamide
T/
TGAI
and
FI,
and
either
certifies
that
the
suppliers
of
beginning
materials
and
the
manufacturing
processes
have
not
changed
since
the
last
comprehensive
product
chemistry
reviews
or
submits
complete
updated
product
chemistry
data
packages,
HED
has
no
44
objections
to
the
reregistration
of
pronamide
with
respect
to
product
chemistry
data
requirements.
Toxicology
Although
there
is
confidence
in
the
overall
scientific
quality
of
the
available
toxicity
data,
several
data
gaps
were
identified:
a
developmental
toxicity
study
in
rats,
a
21
day
dermal
toxicity
study,
28
day
inhalation
toxicity
study,
a
dermal
penetration
study
and
a
comparative
thyroid
rat
assay
in
adult
animals
and
offspring.
Residue
Chemistry
A
review
of
the
product
labels
and
the
supporting
residue
data
indicate
the
following
label
amendments
and
data
submissions
are
required:
C
additional
residue
data
are
required
for:
use
on
grasses,
dried
winter
peas
(outstanding),
the
vines
and
hay
of
winter
peas,
grass
forage,
and
hay.
C
label
amendments
are
required
for
alfalfa
grown
for
seed,
lettuce,
and
peas
(winter);
see
chemistry
chapter
for
details;
C
label
revisions
should
be
made
for
rotational
crops
as
listed:
1.
30
day
plantback
interval
for
leafy
vegetables
(except
Brassica
vegetables)
(Crop
Group
4);
2.
90
day
plantback
interval
for
root
and
tuber
vegetables
(Crop
Group
1);
3.
360
day
plantback
interval
for
cereal
grains
(Crop
Group
15)
and
the
forage,
fodder,
and
straw
of
cereal
grains
(Crop
Group
16).
For
purposes
of
reregistration,
no
additional
plant
metabolism
studies
are
required;
however,
because
the
available
metabolism
studies
were
only
conducted
on
alfalfa
and
lettuce,
the
Agency
may
require
additional
metabolism
studies
in
the
future
should
the
registrants
seek
for
additional
uses
on
other
crop
groups.
The
registrant
is
required
to
further
optimize/
improve
the
revised
animal
enforcement
method
(TR
34
91
68)
to
yield
acceptable
recoveries
at
a
fortification
level
equal
to
established
animal
tolerances.
Following
method
improvement,
the
registrant
is
required
to
submit
bridging
independent
laboratory
validation
data;
the
required
ILV
data
should
include
two
control
samples
fortified
at
0.4
ppm,
the
reassessed
tolerance
level
for
the
kidney
and
liver
of
ruminants.
Additional
confirmatory
storage
stability
data
for
the
regulated
pronamide
metabolites
on
alfalfa,
apples,
grapes,
lettuce,
and
peaches
or
plums
are
required.
| epa | 2024-06-07T20:31:42.743838 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0159-0010/content.txt"
} |
EPA-HQ-OPP-2002-0159-0011 | Supporting & Related Material | "2002-07-12T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
July
5,
2002
CERTIFIED
MAIL
Dear
Registrant:
This
is
the
Environmental
Protection
Agency's
(hereafter
referred
to
as
EPA
or
the
Agency)
"Report
of
FQPA
Tolerance
Reassessment
Progress
and
Interim
Risk
Management
Decision"
(TRED)
for
pronamide
that
was
completed
on
July
5,
2002.
A
Notice
of
Availability,
soliciting
public
comment
for
a
30
day
period,
will
be
published
in
the
Federal
Register
(FR)
shortly.
The
Federal
Food
Drug
and
Cosmetic
Act
(FFDCA),
as
amended,
requires
EPA
to
reassess
all
the
tolerances
for
registered
chemicals
in
effect
on
or
before
the
date
of
the
enactment
of
the
Food
Quality
Protection
Act
(FQPA)
in
August
of
1996
against
the
new
safety
standard
adopted
in
the
FQPA.
In
reassessing
these
tolerances,
the
Agency
must
consider,
among
other
things,
aggregate
risks
from
non
occupational
sources
of
pesticide
exposure,
whether
there
is
increased
susceptibility
to
infants
and
children,
and
the
cumulative
effects
of
pesticides
with
a
common
mechanism
of
toxicity.
The
tolerances
are
considered
reassessed
once
the
safety
finding
has
been
made
or
a
modification
or
revocation
occurs.
A
reregistration
eligibility
decision
(RED)
for
pronamide,
was
completed
May
1994,
prior
to
FQPA
enactment.
Therefore,
it
needed
to
be
updated
to
reassess
the
tolerances
under
the
FQPA
standard.
The
Agency
has
evaluated
the
dietary
risk
associated
with
pronamide
and
has
determined
that,
provided
the
risk
mitigation
measures
outlined
in
this
document
are
implemented,
there
is
a
reasonable
certainty
that
no
harm
to
any
population
subgroup
will
result
from
aggregate
exposure
to
pronamide
when
considering
dietary
exposure
and
all
other
non
occupational
sources
of
pesticide
exposure
for
which
there
is
reliable
information.
Therefore,
the
tolerances
established
for
residues
of
pronamide
in/
on
raw
agricultural
commodities
are
now
considered
reassessed
as
safe
under
section
408(
q)
of
the
FFDCA.
FQPA
requires
that
EPA
consider
"available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"other
substances
that
have
a
common
mechanism
of
toxicity."
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
lowlevel
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect,
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
2
EPA
did
not
perform
a
cumulative
risk
assessment
as
part
of
this
tolerance
reassessment
review
of
pronamide,
because
the
Agency
has
not
determined
if
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
pronamide.
If
EPA
identifies
other
substances
that
share
a
common
mechanism
of
toxicity
with
pronamide,
then
a
cumulative
risk
assessment
will
be
conducted
that
includes
pronamide
once
the
final
framework
EPA
will
use
for
conducting
cumulative
risk
assessments
is
available.
Further,
EPA
is
in
the
process
of
developing
criteria
for
characterizing
and
testing
endocrine
disrupting
chemicals
and
plans
to
implement
an
Endocrine
Disruptor
Screening
Program.
Pronamide
will
be
reevaluated
at
that
time
and
additional
studies
may
be
required.
The
Agency's
human
health
findings
for
the
pesticide
pronamide,
were
discussed
in
a
closure
conference
call
held
on
June
28,
2002,
and
are
summarized
in
the
attached
chemical
overview
of
the
risk
assessments.
These
risk
assessments
and
other
documents
pertaining
to
the
pronamide
tolerance
reassessment
decision
are
listed
at
the
end
of
this
document
and
are
available
on
the
Internet
at
http://
www.
epa.
gov/
pesticides/
reregistration/
status.
htm
and
in
the
public
docket
for
viewing.
Pronamide
tolerances
are
established
under
40
CFR
§180.317
(a),
(b)
and
(c).
The
tolerance
expression,
listed
in
(a)
and
(c),
is
in
terms
of
the
combined
residues
of
the
herbicide
propyzamide
and
its
metabolites
(containing
the
3,
5
dichlorobenzoyl
moiety
and
calculated
as
3,
5
dichloro
N
(1,1
dimethyl
2
propynyl)
benzamide).
The
tolerance
expression,
listed
in
(b),
is
in
terms
of
the
parent
only.
The
Agency
recommends
that
the
tolerance
expression
under
(b)
be
modified
to
include
the
metabolites.
The
Agency
also
recommends
the
following:
C
Decreasing
the
established
tolerance
for
artichokes;
C
Increasing
the
tolerances
for
cattle
fat,
goat
fat,
hog
fat,
horses
fat,
and
sheep
fat;
C
Revoking
the
tolerance
for
poultry
kidney
and
grass,
forage;
and,
C
Proposing
a
tolerance
for
alfalfa
seed
and
pea
vines
and
hay.
The
Table
below
summarizes
EPA's
tolerance
reassessment
decision
which
accounts
for
47
tolerance
reassessments.
The
Codex
Commission
has
established
several
maximum
residue
limits
(MRLs)
for
residues
of
pronamide
in/
on
various
raw
agricultural
and
processed
commodities.
The
Codex
MRLs
are
expressed
in
terms
of
pronamide
per
se.
The
Codex
MRLs
and
the
U.
S.
tolerances
will
be
incompatible
when
the
U.
S.
tolerance
expression
for
plant
commodities
is
revised
to
include
residues
of
pronamide
and
the
metabolites.
3
Tolerance
Reassessment
Summary
for
Pronamide
Commodity
Established
Tolerance
(ppm)
Reassessed
Tolerance
(ppm)
Comment
Correct
Commodity
definition
Tolerances
Listed
Under
40
CFR
§180.317(
a)
Apples
0.1
0.
1
Artichokes
0.1
0.
01
Residues
of
pronamide
and
its
metabolites
containing
the
3,5
dichlorobenzoyl
moiety
were
nondetectable
(less
than
the
level
of
concern
(LOC)
of
0.01ppm)
in/
on
each
sample
of
artichokes
harvested
61
days
following
a
single
application
of
a
representative
pronamide
formulation
at
4.0
or
8.0
lb
ai/
A.
Blackberries
0.05
0.05
Blueberries
0.05
0.05
Boysenberries
0.05
0.05
Cattle,
fat
0.02
0.20
Fat
tolerance
raised
due
to
linear
extrapolation
of
maximum
residues
observed
in
fat
at
40
ppm
feeding
level
relative
to
the
Maximum
theoretical
dietary
burdens
(MTDB)
Cattle,
kidney
0.
4
0.4
Cattle,
liver
0.4
0.
4
Cattle,
mbyp
(except
kidney,
liver)
0.
02
0.
02
Cattle,
meat
0.02
0.02
Eggs
0.02
0.02
Endive
(escarole)
1.0
1.
0
Goats,
fat
0.02
0.20
Fat
tolerance
raised
due
to
linear
extrapolation
of
maximum
residues
observed
in
fat
at
40
ppm
feeding
level
relative
to
the
MTDB
Goats,
kidney
0.4
0.
4
Goats,
liver
0.4
0.
4
Goats,
mbyp
(except
kidney,
liver)
0.
02
0.
02
Goats,
meat
0.02
0.02
Grapes
0.1
0.
1
Hogs,
fat
0.
02
0.
20
Fat
tolerance
raised
due
to
linear
extrapolation
of
maximum
residues
observed
in
fat
at
40
ppm
feeding
level
relative
to
the
MTDB
Hogs,
kidney
0.
4
0.4
Hogs,
liver
0.4
0.
4
Hogs,
mbyp
(except
kidney)
0.02
0.02
Hogs,
meat
0.02
0.02
Horses,
fat
0.
02
0.
20
Fat
tolerance
raised
due
to
linear
extrapolation
of
maximum
residues
observed
in
fat
at
40
ppm
feeding
level
relative
to
the
MTDB
Commodity
Established
Tolerance
(ppm)
Reassessed
Tolerance
(ppm)
Comment
Correct
Commodity
definition
4
Horses,
kidney
0.
4
0.4
Horses,
liver
0.4
0.
4
Horses,
mbyp
(except
kidney)
0.02
0.02
Horses,
meat
0.02
0.02
Lettuce
1.0
1.
0
Lettuce
Head
Only
head
lettuce
is
supported
by
acceptable
data;
leaf
lettuce
uses
must
be
removed
from
the
label.
Alternatively,
the
label
may
be
revised
to
specify
a
practical
PHI
(35
day)
for
leaf
lettuce
and
supporting
data
be
submitted.
Milk
0.02
0.02
Non
grass
animal
feeds
10.0
10.0
Non
grass
animal
feeds
(forage,
fodder,
straw,
and
hay)
group
Pears
0.
1
0.1
Poultry,
fat
0.
02
0.
02
Poultry,
kidney
0.
2
Revoke
Tolerances
are
typically
not
established
for
poultry
kidneys.
Poultry,
liver
0.2
0.
2
Poultry,
mbyp
(except
kidney,
liver)
0.02
0.02
Poultry,
meat
0.02
0.02
Radicchio,
greens
(tops)
2.
0
2.0
Raspberries
0.05
0.05
Sheep,
fat
0.
02
0.
20
Fat
tolerance
raised
due
to
linear
extrapolation
of
maximum
residues
observed
in
fat
at
40
ppm
feeding
level
relative
to
the
MTDB
Sheep,
kidney
0.
4
0.4
Sheep,
liver
0.4
0.
4
Sheep,
mbyp
(except
kidney,
liver)
0.02
0.02
Sheep,
meat
0.02
0.02
Stone
fruit
0.1
0.
1
Commodity
Established
Tolerance
(ppm)
Reassessed
Tolerance
(ppm)
Comment
Correct
Commodity
definition
5
Tolerances
To
Be
Proposed
Under
40
CFR
§180.317(
a)
Alfalfa
Seed
10.0
Tolerance
recommendation
is
contingent
upon
required
label
revision
to
specify
a
50
day
PHI
and
a
maximum
seasonal
rate
of
2.0
lb
ai/
A
Tolerances
Listed
Under
40
CFR
§180.317(
b)
Cranberries
0.05
Temporary
tolerance
associated
with
a
FIFRA
section
18
that
will
expire
12/
31/
03.
Grass,
forage
1.0
Tolerance
expired
12//
31/
01.
Tolerances
Listed
Under
40
CFR
§180.317(
c)
Peas,
dried
0.
05
TBD
Pea,
field,
seed.
European
data
currently
used
to
support
tolerance.
Registrant
needs
to
submit
field
trial
data
as
confirmatory
data.
Rhubarb
0.1
0.
1
Tolerances
To
Be
Proposed
Under
40
CFR
§180.317(
c)
Pea,
field,
hay
–
TBD
Pea,
field
vines
–
TBD
*TBD=
To
Be
Determined
Risk
Mitigation:
As
a
result
of
risk
concerns
for
children
identified
in
the
March
8,
2002
risk
assessment,
Dow
AgroSciences
agreed
to
voluntarily
cancel
all
product
labeled
for
residential
use
(EPA
Reg.
No.
8660
85;
see
67
FR
13627).
Additionally,
in
order
to
further
address
this
risk
concern
and
minimize
the
likelihood
of
non
dietary
exposure
to
children,
the
following
label
statement
must
appear
on
Pronamide
end
use
products:
"This
product
may
only
be
used
on
turf
grown
for
seed
or
sod
or
on
nonresidential
sites
including
golf
course,
industrial
and
office
building
sites,
stadium
fields
or
professional
athletic
fields."
To
minimize
adult
non
occupational
exposure,
the
following
label
statement
must
appear
on
Pronamide
end
use
products:
"For
all
uses
except
those
specified
below,
do
not
enter
or
allow
others
to
enter
until
sprays
have
dried.
When
applied
to
stadium
or
professional
athletic
fields,
water
in
immediately
after
application
or,
do
not
enter
or
allow
others
to
enter
treated
area
for
24
hours
after
application.
If
product
is
watered
in
after
treatment,
do
not
enter
or
allow
other
persons
to
enter
until
area
had
dried"
6
The
risk
assessment
also
identified
a
slight
cancer
risk
due
to
pronamide
exposure
in
drinking
water
from
surface
water
sources
(EECs
are
4.3
ppb
compared
to
the
cancer
DWLOC
of
1.1
ppb).
However,
the
Agency
is
not
concerned
because
of
the
conservative
inputs
used
in
the
surface
water
modeling.
The
PRZM
EXAMS
assessment
was
based
on
the
maximum
label
rates
for
pronamide,
whereas
typical
rates
for
many
crops
are
25%
50%
less.
The
model
also
assumed
a
Percent
Crop
Area
(PCA)
of
87%,
which
is
likely
to
be
an
overestimate
for
the
crops
being
considered.
In
addition,
pronamide
data
exists
for
only
one
soil
in
the
aerobic
soil
metabolism
study.
When
aerobic
soil
metabolism
data
is
only
available
in
one
soil,
a
conservative
extrapolation
factor
is
used
which
is
likely
to
contribute
to
over
estimating
potential
persistence
and
exposure.
As
a
result,
Dow
AgroSciences
has
agreed
to
conduct
an
aerobic
soil
metabolism
study
(two
additional
soils)
and
an
aerobic
aquatic
metabolism
study
as
confirmatory
data.
The
Agency
will
be
issuing
a
generic
Data
Call
In
(DCI)
that
outlines
further
data
requirements
for
this
chemical.
The
following
additional
data
are
required
for
pronamide.
The
registrants
of
pronamide
must
respond
within
90
days
of
receipt
of
this
letter
from
the
Agency.
Most
pertinent
product
chemistry
data
requirements
are
satisfied
for
technical
grade
active
ingredients.
The
following
is
required:
°
Product
Chemistry
GDLN
Description
860.1200
Direction
for
use
860.1380
Storage
Stability
Data
Additional
data
are
also
required
for
the
51%
Formulation
Intermediate
(FI)
concerning
the
following:
GDLN
Description
830.6314
oxidation/
reduction
830.6316
explodability
830.6317
storage
stability
830.6320
corrosion
characteristics
The
registrant
must
either
certify
that
the
supplier
of
beginning
materials
and
the
manufacturing
processes
have
not
changed
since
the
last
comprehensive
product
chemistry
reviews
or
submit
complete
updated
product
chemistry
data
packages.
7
Although
there
is
confidence
in
the
overall
scientific
quality
of
the
available
toxicity
data,
several
data
gaps
were
identified
which
are
required
to
fulfill
the
OPPTS
harmonized
test
guidelines:
°
Toxicity
GDLN
Description
870.3700
developmental
study
in
rats
Non
GDLN
comparative
thyroid
rat
assay
in
adult
animals
and
offspring
870.3200
21
day
dermal
toxicity
study
Non
GDLN
28
day
inhalation
study
870.7600
dermal
penetration
study
A
review
of
registered
uses
and
the
supporting
residue
chemistry
data
indicates
the
following
residue
data
are
required:
°
Residue
(GDLN
860.1500
Crop
Field
Trials)
dried
winter
peas
vines
and
hay
of
winter
peas
Confirmatory
storage
stability
data
(GDLN
860.1380)
are
required
for
regulated
pronamide
metabolites
on
the
following:
alfalfa
apples
grapes
lettuce
peaches
plums
A
confirmatory
aerobic
soil
metabolism
study
(835.4100)
and
an
aerobic
aquatic
metabolism
study
(835.4300)
are
required.
The
registrant
is
required
to
further
optimize/
improve
the
revised
animal
enforcement
method
(TR
34
91
68)
to
yield
acceptable
recoveries
at
a
fortification
level
equal
to
established
animal
tolerances.
Following
method
improvement,
the
registrant
is
required
to
submit
bridging
independent
laboratory
validation
(ILV)
data;
the
required
ILV
data
should
include
two
control
samples
fortified
at
0.4
ppm,
the
reassessed
tolerance
level
for
the
kidney
and
liver
of
ruminants.
8
The
following
label
amendments
are
required
for
lettuce,
peas,
and
alfalfa
grown
for
seed:
GDLN
Description
860.1850
Confined
Accumulation
in
Rotational
Crops
860.1900
Field
Accumulation
in
Rotational
Crops
°
30
day
plant
back
interval
for
leafy
vegetables
(except
Brassica
vegetables)
°
90
day
plant
back
interval
for
root
and
tuber
vegetables
°
360
day
plant
back
interval
for
cereal
grains,
forage
and
fodder,
and
straw
of
cereal
grain
If
you
have
questions
on
this
document,
please
contact
the
Chemical
Review
Manager,
Cecelia
Watson,
at
(703)
305
4329.
For
questions
regarding
label
changes
and
registration
action,
please
contact
Jim
Tompkins
of
the
Registration
Division
at
(703)
305
5697.
Sincerely,
Lois
A.
Rossi,
Director
Special
Review
and
Reregistration
Division
Enclosures:
C
Overview
and
Summary
of
Pronamide
(Propyzamide)
Risk
Assessment
C
Hazard
Identification
Assessment
Review
Committee
(HIARC)
report
(M.
Centra,
December
10,
2001)
C
Report
of
the
FQPA
Safety
Factor
Committee
(C.
Christensen,
December
19,
2001)
C
Toxicology
Chapter
of
the
Tolerance
Reassessment
Eligibility
Decision
(TRED)
(M.
Centra,
March
7,
2002)
C
Report
of
the
Mechanism
of
Toxicity
Assessment
Review
Committee
(MTARC)
(M.
Centra,
January
21,
2001)
C
Review
of
Pronamide
Incident
Reports
(
J.
Blondell
&
M..
Spann,
August
12,
2001)
C
Chronic
and
Cancer
Dietary
Exposure
Assessments
(D.
Soderberg,
et
al.,
February
7,
2002)
C
Pronamide
Residue
Chemistry
chapter
(J.
Morales,
February
28,
2002)
C
Residential
Risk
Assessment,
(B.
O'Keefe,
March
7,
2002)
C
Drinking
Water
Assessment
to
Support
TRED
for
Propyzamide
(Pronamide)
(L.
Shanaman,
May
16,
2001)
C
Addendum
to
EPA
March
8,
2002:
Pronamide.
Tolerance
Reassessment
Eligibility
Decision
(TRED).
(G.
Bangs
May
21,
2002)
C
Tier
II
Water
Assessment
to
Support
TRED
for
Pronamide
(Propyzamide)
(L.
Shanaman,
May
31,
2002).
| epa | 2024-06-07T20:31:42.761689 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0159-0011/content.txt"
} |
EPA-HQ-OPP-2002-0159-0012 | Supporting & Related Material | "2002-07-12T04:00:00" | null | OVERVIEW
OF
PRONAMIDE
(Propyzamide)
RISK
ASSESSMENT
Introduction
The
Agency
has
completed
its
review
of
the
available
data
for
the
herbicide
pronamide
and
is
announcing
its
tolerance
reassessment
decision.
This
document
summarizes
EPA's
human
health
findings
and
conclusions
as
presented
fully
in
the
documents
entitled
"Pronamide
Tolerance
Reassessment
Eligibility
Decision
(TRED)"
dated
March
8,
2002,
"Pronamide
Revised
Aggregate
Risk
Estimates
Addendum
to
EPA
March
8,
2002"
dated
May
21,
2002
and
related
documents
supporting
this
decision.
The
purpose
of
this
overview
is
to
assist
the
reader
by
identifying
the
key
features
and
findings
of
the
risk
assessment
in
order
to
enhance
understanding
of
the
conclusions
reached
in
the
tolerance
reassessment
decision.
The
Agency's
reassessment
of
aggregate
risk,
including
exposure
through
food,
drinking
water,
and
residential
exposure
is
required
by
the
Federal
Food,
Drug,
and
Cosmetic
Act
(FFDCA).
The
Agency
must
review
tolerances
and
tolerance
exemptions
that
were
in
effect
when
the
Food
Quality
Protection
Act
(FQPA)
was
enacted
in
August
1996
to
ensure
that
these
existing
pesticide
residue
limits
for
food
and
feed
commodities
meet
the
safety
standard
of
the
new
law.
FFDCA
requires
the
Agency
to
review
all
the
tolerances
for
registered
chemicals
in
effect
on
or
before
the
date
of
the
enactment
of
FQPA.
In
reviewing
these
tolerances,
the
Agency
must
consider,
among
other
things,
aggregate
risks
from
non
occupational
sources
of
pesticide
exposure,
whether
there
is
increased
susceptibility
to
infants
and
children,
and
the
cumulative
effects
of
pesticides
with
a
common
mechanism
of
toxicity.
The
tolerances
are
considered
reassessed
once
the
safety
finding
has
been
made
or
a
tolerance
revocation
occurs.
A
RED
for
pronamide
was
issued
in
May
1994,
prior
to
enactment
of
FQPA;
therefore
it
needed
to
be
updated
to
consider
the
provisions
of
the
Act.
FQPA
requires
that
the
Agency,
when
considering
whether
to
establish,
modify,
or
revoke
a
tolerance,
consider
"available
information"
concerning
the
cumulative
effects
of
the
particular
pesticide's
residues
and
"other
substances
that
have
a
common
mechanism
of
toxicity."
The
Agency
does
not,
at
this
time,
have
sufficient
reliable
information
available
to
determine
whether
pronamide
has
a
common
mechanism
of
toxicity
with
other
substances.
Therefore,
for
the
purposes
of
this
risk
assessment,
the
Agency
has
not
assumed
that
pronamide
has
a
common
mechanism
of
toxicity
with
other
substances.
If
EPA
identifies
other
substances
that
share
a
common
mechanism
of
toxicity
with
pronamide,
a
cumulative
risk
assessment
for
those
substances
will
be
performed.
The
risk
assessment
and
documents
pertaining
to
the
Agency's
report
on
FQPA
tolerance
reassessment
progress
and
risk
management
decision
for
pronamide
are
available
on
the
Internet
at
http://
www.
epa.
gov/
pesticides/
reregistration/
status.
htm
and
in
the
public
docket.
The
Agency's
report
on
FQPA
tolerance
reassessment
progress
and
risk
management
decision
for
pronamide
will
be
announced
in
the
Federal
Register.
2
Use
Profile
Herbicide:
Pronamide
is
a
selective,
pre
emergence
herbicide
registered
for
the
control
of
grassy
and
broadleaf
weeds
on
terrestrial
food
crops
[artichoke,
blackberry,
blueberry,
boysenberry,
cherry,
endive
(escarole),
lettuce,
nectarine,
peach,
pear,
plum,
prune,
raspberry,
(black,
red),
rhubarb];
terrestrial
food
and
feed
crops
(agricultural
fallow/
idleland,
apples,
grapes,
peas,
sugar
beets);
terrestrial
non
food
crops
(Christmas
trees,
clover
plantations,
golf
course
turf,
ornamental
herbaceous
plants,
recreation
area
lawns)
and
outdoor
residential
areas
(ornamental
and/
or
shade
trees,
ornamental
woody
shrubs
and
vines).
Formulations:
Wettable
powder
50%
and
51%
active
ingredient
(a.
i.)
and
technical
grade
92%
a.
i.
Methods
and
Rates
of
Application:
Pronamide
is
produced
and
formulated
for
use
as
a
50
WP
wettable
powder
which
is
packaged
in
water
soluble
pouches
and
then
mixed
in
water
before
application.
Pronamide
is
applied
as
a
liquid
spray.
It
is
a
soil
active
systemic
herbicide
with
uptake
by
susceptible
weeds
occurring
through
the
roots.
Application
rates
range
from
0.5
to
4
lbs
a.
i.
per
acre
per
application
per
year.
Most
crop
sites
have
only
one
application
per
year.
However,
artichokes
have
2
applications
per
year
(at
2
lbs
per
application)
and
gladiolas
have
4
applications
per
year
(at
2
lbs
per
application,
up
to
8
lbs
a.
i.
per
acre
per
application
could
be
applied).
It
is
applied
to
various
food/
feed
crops
using
ground
spray
equipment,
by
hand
held
sprayer,
soil
incorporation,
or
by
aircraft.
Use
Summary:
Based
on
available
pesticide
usage
data
for
1991
through
2001,
total
annual
domestic
usage
of
pronamide
is
approximately
225,000
pounds.
In
terms
of
pounds
a.
i.,
total
usage
is
allocated
mainly
to
head
lettuce
(29%),
other
lettuce
(19%),
seed
crops
(13%),
fallow
land
(11%),
hay
(other
than
alfalfa)
(8%),
horticulture
(3%)
and
alfalfa
(3%).
Sites
with
5%
or
more
of
acreage
treated
include
lettuce
(other
than
head)
(49%),
head
lettuce
(36%),
California
endive/
escarole
(31%),
artichokes
(21%),
blackberries
(6%)
and
raspberries
(5%).
States
with
significant
usage
in
terms
of
pound
a.
i.
include
Arizona,
California,
Oregon
and
Washington.
Pre
harvest
intervals,
where
specified,
are
generally
long,
ranging
from
25
to
180
days.
Classification:
Pronamide
is
a
restricted
use
pesticide.
Registrant:
Dow
AgroSciences
(recently
purchased
from
Rohm
and
Haas).
3
Human
Health
Risk
Assessment
Acute
Dietary
(Food)
Risk
(For
a
complete
discussion,
see
section
4.2
of
the
Human
Health
Risk
Assessment)
No
toxicologic
endpoint
was
identified
as
appropriate
from
a
single
(acute)
dose
of
pronamide.
Consequently
an
acute
dietary
risk
assessment
was
not
performed
for
pronamide.
Chronic
Dietary
(Food)
Risk
(For
a
complete
discussion,
see
section
4.2
of
the
Human
Health
Risk
Assessment
Chronic
dietary
risk
is
calculated
by
using
the
average
consumption
value
for
food
and
average
residue
values
on
those
foods
over
a
70
year
lifetime.
A
risk
estimate
that
is
less
than
100%
of
the
chronic
population
adjusted
dose
(cPAD)
(the
dose
at
which
an
individual
could
be
exposed
over
the
course
of
a
lifetime
and
no
adverse
health
effects
would
be
expected)
is
not
of
concern.
The
cPAD
is
the
chronic
reference
dose
(cRfD)
adjusted
for
the
FQPA
Safety
Factor.
The
assessment
showed
that
the
chronic
dietary
risk
estimates
are
not
of
concern,
<1%
of
the
cPAD,
for
the
U.
S.
population
and
for
all
subgroups.
°
The
toxicity
endpoint
for
the
chronic
dietary
assessment
is
based
on
increased
relative
liver
weight
and
non
neoplastic
histological
changes
in
the
liver,
thyroid,
and
ovaries
in
a
combined
chronic
toxicity/
carcinogenicity
study
in
the
rat.
The
no
observable
adverse
effect
level
(NOAEL)
is
8.46
mg/
kg/
day.
The
lowest
observed
adverse
effect
level
(LOAEL)
is
42.6
mg/
kg/
day.
°
The
Uncertainty
Factor
(UF)
is
100X;
10X
for
intraspecies
variation
and
10X
for
interspecies
extrapolation.
°
The
10x
FQPA
Safety
Factor
was
reduced
to
3x
for
the
following
reasons:
1.
The
toxicological
database
is
adequate
for
FQPA
assessment.
2.
There
was
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
of
rabbits
to
in
utero
exposure
or
to
rats
following
pre/
postnatal
exposure.
Although
the
developmental
toxicity
study,
was
unacceptable
because
a
definitive
NOAEL
as
well
as
a
LOAEL
were
not
established,
no
increased
susceptibility
was
seen
at
the
highest
dose
tested.
3.
A
developmental
neurotoxicity
study
is
not
required.
4.
The
dietary
(food
and
drinking
water)
and
residential
exposure
assessments
will
not
underestimate
the
potential
exposures
for
infants
and
children.
5.
A
3x
was
retained
because
of
evidence
of
endocrine
organ
toxicity
in
the
thyroid,
testes,
ovaries,
adrenal
glands,
pituitary
gland,
thymus.
4
For
a
more
complete
discussion
see
the
December
3,
2001
FQPA
Safety
Factor
Committee
report
and
section
5.6
of
the
Pronamide
(Propyzamide):
Report
of
the
Hazard
Identification
Assessment
Review
Committee
(HIARC)
Meeting
for
the
Herbicide,
Pronamide.
°
The
Dietary
Exposure
Evaluation
Model
(DEEM)
was
used
to
estimate
chronic
dietary
exposure.
A
refined
Tier
3
analysis
was
performed
using:
1)
percent
crop
treated;
2)
anticipated
residues
for
meat,
milk,
poultry
and
eggs;
3)
FDA
and
PDP
monitoring
data;
and,
4)
tolerance
level
residues
for
4
crops.
°
The
cPAD
is
0.03
mg/
kg/
day
(chronic
RfD
0.08
mg/
kg/
day
÷
3x
FQPA
safety
factor).
Cancer
Dietary
Risk
(Food)
(For
a
complete
discussion,
see
section
4.2
of
the
Human
Health
Risk
Assessment)
The
cancer
risk
is
calculated
by
using
the
average
consumption
value
for
food
and
average
residue
values
on
those
foods
over
a
70
year
lifetime.
The
chronic
exposure
value
is
typically
combined
with
a
linear,
low
dose
approach
(Q1
(
)
to
determine
the
lifetime
(cancer)
risk
estimate.
The
Agency
generally
considers
risks
greater
than
1x10
6
(i.
e.,
greater
than
one
in
a
million)
not
of
concern.
°
Pronamide
was
previously
classified
as
a
Group
B2
chemical,
probable
human
carcinogen,
based
on
thyroid
follicular
cell
adenomas
(males
and
females)
and
benign
testicular
interstitial
cell
tumors
(males)
in
rats
and
hepatocellular
carcinomas
in
male
mice.
°
A
linear,
low
dose
approach
(Q1
(
)
is
used
for
human
risk
characterization.
The
cancer
potency
unit
risk
(Q1
(
)
based
on
male
mouse
liver
adenoma
and/
or
carcinoma
combined
tumor
rates
is
2.59x10
2
(mg/
kg/
day)
1
in
human
equivalents
[converted
from
animals
to
humans
by
use
of
the
(mg/
kg
body
weight)
¾
interspecies
scaling
factor].
°
The
cancer
food
risk
estimate
is
1.06x10
7
for
the
U.
S.
population,
and
does
not
exceed
the
Agency's
level
of
concern
(1.0x10
6
or
one
in
one
million).
Residential
Risk
(For
a
complete
discussion,
see
section
4.4
of
the
Human
Health
Risk
Assessment)
As
a
result
of
risk
concerns
for
children
identified
in
the
March
8,
2002
risk
assessment,
the
registrant
agreed
to
voluntarily
cancel
a
product
labeled
for
the
residential
use
(EPA
Reg.
No.
8660
85;
see
67
FR
13627).
Additionally,
the
registrant
agreed
to
further
limit
use
to
turf
grown
for
seed
or
sod
and
non
residential
sites
including
golf
courses,
industrial
and
office
building
sites,
stadium
fields
or
professional
athletic
fields.
These
risk
mitigation
measures
5
make
children's
non
dietary
exposure
unlikely.
To
minimize
adult
residential
exposure
related
to
the
sites
listed
above,
the
registrant
has
agreed
to
amend
pronamide
labels
to
require
24
hour
restricted
entry
interval
or
require
watering
in
as
soon
as
possible
after
application.
Given
these
proposed
restrictions
on
the
use
of
pronamide
on
turf,
high
contact
dermal
scenarios
are
not
likely
to
occur.
Therefore,
the
sole
exposure
scenario
for
the
residential
risk
assessment
is
based
on
low
contact
activity
which
is
represented
and
estimated
by
golf
course
reentry.
The
route
of
exposure
is
dermal.
The
population
at
risk
is
adults.
The
dermal
exposure
estimates
are
considered
somewhat
refined,
since
turf
transferrable
residue
(TTR)
data
from
a
pronamide
TTR
field
study
was
used.
However,
both
the
short
term
exposure
estimates
and
the
cancer
risk
estimates
relied
on
a
100%
dermal
absorption
factor,
which
results
in
high
end
dose
estimates.
Therefore,
a
dermal
absorption
study
would
help
to
reduce
these
risk
estimates.
A
3x
FQPA
Safety
Factor
is
required
for
all
population
subgroups
when
assessing
residential
exposures
of
all
durations.
The
rationale
for
reducing
the
safety
factor
is
the
same
as
listed
under
the
chronic
dietary
risk
discussion.
Short
Term
C
For
short
term
(1
30)
incidental
oral
exposures
an
adjusted
dose
of
8.46
mg/
kg/
day
was
established
for
use
in
the
risk
assessment.
This
dose
is
derived
from
the
NOAEL
from
a
chronic
toxicity/
carcinogenicity
study
in
rats,
where
the
effects
are
increased
liver
weight
and
non
neoplastic
histologic
changes
in
the
liver,
thyroid,
and
ovaries
observed
at
the
LOAEL
of
42.6
mg/
kg/
day.
The
dose
selection
is
based
on
a
maternal
toxicity
NOAEL
of
5
mg/
kg/
day
and
clinical
signs
of
toxicity
(soiled
anal
area
and
anorexia)
and
liver
effect
(punctate
vacuolation
of
hepatocytes)
observed
at
the
LOAEL
of
20
mg/
kg/
day
in
the
developmental
toxicity
study
conducted
in
rabbits.
Although
this
study
is
of
the
appropriate
route
(oral)
and
duration
(13
days),
the
NOAEL
(5
mg/
kg/
day)
in
this
study
is
lower
than
the
NOAEL
(8.46
mg/
kg/
day)
established
in
the
chronic
toxicity/
carcinogenicity
study
in
the
rat.
The
apparent
disparity
between
these
NOAELs
is
driven
by
the
doses
of
pronamide
selected
for
testing
in
these
studies.
The
Agency
concluded
that
using
a
more
realistic
NOAEL
of
8.46
mg/
kg/
day,
rather
than
5
mg/
kg/
day,
would
provide
a
sufficiently
protective
dose
for
risk
assessment.
°
The
short
term
dermal
endpoint
has
a
10x
UF
for
intraspecies
variability
and
10x
UF
for
interspecies
extrapolation.
When
considering
the
FQPA
Safety
Factor
of
3x,
MOEs
must
be
$
300
to
be
above
the
Agency's
level
of
concern.
°
The
short
term
exposure
estimates
are
considered
high
end
estimates,
since
the
maximum
application
rate
is
used,
a
100%
dermal
absorption
factor
is
assumed
and
exposures
are
assumed
to
occur
on
the
day
of
treatment.
°
The
exposure
scenario
is
based
on
low
contact
activity
golf
course
reentry.
The
route
of
exposure
is
dermal.
The
population
at
risk
are
adults.
6
°
The
short
term
Margin
of
Exposure
(MOE)
for
golf
course
reentry
using
zero
day
after
treatment
(DAT
0)
turf
transferable
residue
data
from
the
turf
study
is
1000.
Therefore,
the
Agency
is
not
concerned
about
short
term
residential
exposure
to
pronamide.
Intermediate
Term
No
intermediate
or
long
term
exposure
scenarios
(i.
e.,
greater
than
30
days)
are
anticipated
based
on
the
results
of
the
turf
transferable
residue
(TTR)
study
which
showed
that
residues
dissipate
to
below
the
level
of
quantification
by
day
14
following
application.
Cancer
Risk
°
As
stated
previously,
pronamide
is
classified
as
a
Group
B2
chemical,
probable
human
carcinogen
with
inadequate
evidence
in
humans.
°
The
cancer
potency
(Q1*)
is
2.59
x
10
2
(mg/
kg/
day)
1
in
human
equivalents.
°
The
adult
golfer
cancer
risk
is
estimated
at
1.15
x
10
7
.
In
order
to
exceed
the
cancer
risk
(1.0
x
10
6
),
an
exposure
frequency
of
8.7
days
per
year
would
be
needed
for
the
activity
of
golf.
Because
pronamide
is
applied
one
time
per
year,
the
Agency
does
not
believe
this
exposure
frequency
will
occur.
Therefore,
the
cancer
risk
for
golfers
does
not
exceed
the
Agency's
level
of
concern.
Drinking
Water
Dietary
Risk
(For
a
complete
discussion,
see
section
4.3
of
the
Human
Health
Risk
Assessment)
Drinking
water
exposure
to
pesticides
can
occur
through
groundwater
and
surface
water
contamination.
EPA
considers
both
acute
(one
day)
and
chronic
(lifetime)
drinking
water
risks
and
uses
either
modeling
or
actual
monitoring
data,
if
available,
to
estimate
those
risks.
°
A
Tier
I
Drinking
Water
Assessment
for
pronamide
was
conducted
using
the
SCI
GROW
model
for
groundwater.
The
Tier
I
groundwater
estimates
were
predicted
from
application
of
pronamide
at
the
maximum
label
rate
(2
lbs
active
ingredient
per
acre
four
times
per
year)
for
ornamental
herbaceous
plants,
and
represent
upper
bound
estimates
of
the
concentrations
that
might
be
found
in
groundwater
due
to
the
use
of
pronamide/
propyzamide.
The
resulting
modeled
groundwater
screening
concentration
is
1.1
ppb.
°
The
Tier
II
PRZM
EXAMS
model
was
used
to
predict
EECs
for
pronamide
in
surface
water.
Conservative
inputs
were
used
for
the
environmental
(soil
and
water
metabolism)
assumptions,
(i.
e.,
2x
and
3x
extrapolation
factors
were
applied
to
soil
and
water
halflives
used
in
the
PRZM
EXAMS
assessment).
Maximum
label
application
rates
were
7
used
for
major
crops.
The
chronic
EEC
values
ranged
from
0.53
to
4.45
ppb
(the
low
end
crop
was
lettuce
in
Florida,
and
the
high
end
crop
was
alfalfa
in
California).
Using
the
36
year
mean
concentration
values
for
cancer
risk
estimates,
the
average
exposure
values
ranged
from
0.54
to
4.3
ppb.
°
Although
there
is
no
legal
requirement
under
the
Safe
Drinking
Water
Act
to
monitor
for
pronamide,
it
has
been
detected
in
surface
and
groundwater
in
various
locations
in
the
U.
S.
The
maximum
level
detected
was
0.365
ppb
(surface
water)
at
Zollner
Creek
near
Mt.
Abgel,
Oregon
on
Nov.
16,
1998
and
the
range
was
0.0037
to
0.365
ppb
(surface
water)
(USGS
NAWQA).
The
maximum
ground
water
detection
was
at
Benton
Ozark,
AK
at
0.82
ppb
on
April
13,
1994,
and
ranging
from
0.005
0.82
ppb.
°
Short
term
and
chronic
drinking
water
exposure
to
pronamide
did
not
result
in
a
risk
estimate
of
concern
for
non
cancer
risks.
The
short
term
EECs
ranged
between
3.7
to
10.3
ppb,
depending
on
the
crop,
compared
to
the
DWLOC
which
ranged
from
560
to
700
ppb.
The
chronic
non
cancer
EECs
ranged
between
0.53
to
4.45
ppb,
depending
on
the
crop,
compared
to
the
chronic
DWLOC
which
ranged
between
300
to
1050
ppb.
°
There
are
cancer
risk
estimates
which
slightly
exceed
the
Agency's
level
of
concern.
While
the
modeled
groundwater
EEC
is
1.1
ppb
compared
to
the
cancer
DWLOC
1.06
ppb,
the
modeled
surface
water
EECs
exceed
the
DWLOC
for
some
crops
(the
surface
water
cancer
EECs
range
from
0.54
to
4.3
ppb).
Aggregate
Risk
(For
a
complete
discussion,
see
section
5.0
of
the
Human
Health
Risk
Assessment
and
Addendum
to
EPA
March
8,
2002:
Pronamide.
Tolerance
Reassessment
Eligibility
Decision
(TRED))
FQPA
requires
an
aggregate
risk
assessment
to
be
conducted
considering
all
nonoccupational
sources,
including
exposure
from
water,
food,
and
residential
use.
Because
there
are
potential
exposures
to
treated
turf,
the
aggregate
exposure
assessment
for
pronamide
includes
exposure
estimates
from
residential
sources
as
well
as
food
and
drinking
water.
The
Agency
uses
a
drinking
water
level
of
comparison
(DWLOC)
as
a
surrogate
to
capture
risk
associated
with
exposure
from
pesticides
in
drinking
water.
The
DWLOCs
represent
the
maximum
contribution
to
the
human
diet
(in
ppb
or
:
g/
L)
that
may
be
attributed
to
residues
of
a
pesticide
in
drinking
water
after
dietary
exposure
is
subtracted
from
the
chronic
Population
Adjusted
Dose
(cPAD)
or
cPAD.
Risks
from
drinking
water
are
assessed
by
comparing
the
DWLOCs
to
the
estimated
environmental
concentrations
(EECs)
in
surface
water
and
groundwater.
If
the
EEC
is
less
than
the
DWLOC,
there
is
generally
no
drinking
water
concerns.
The
EECs
for
average
concentrations
of
pronamide
were
based
on
PRZM
EXAMS
for
surface
water
and
SCI
GROW
for
groundwater.
Drinking
water
modeling
is
considered
to
be
an
unrefined
assessment
and
provides
high
end
estimates.
8
Short
Term
Risk
The
short
term
food,
water,
and
low
contact
dermal
(golfing)
pronamide
exposures
were
aggregated
in
the
Risk
Assessment,
and
the
estimated
environmental
concentration
(EECs)
for
surface
water
(3.69
to
10.3
ppb)
and
ground
water
(1.1
ppb),
modeled
using
SCI
GROW
and
PRZM
EXAMS,
did
not
exceed
the
DWLOC
(range
560
700
ppb).
Therefore,
risk
estimates
for
all
pathways
of
exposure
are
not
of
concern
for
pronamide
short
term
exposure
when
pronamide
use
is
restricted
per
the
label
changes
cited
above.
Chronic
Risk
Due
to
the
short
term,
intermittent
nature
of
residential
exposure
to
pronamide,
only
dietary
and
water
intake
were
included
in
the
chronic
aggregate
exposure
estimate.
The
chronic
DWLOC
is
the
concentration
in
drinking
water
as
a
part
of
the
aggregate
chronic
exposure
that
occupies
no
more
than
100%
of
the
cPAD
when
considered
together
with
other
sources
of
exposure.
To
calculate
the
chronic
DWLOC
exposure
relative
to
a
chronic
toxicity
endpoint,
the
chronic
dietary
food
exposure
(from
DEEM™)
was
subtracted
from
the
chronic
PAD
to
obtain
the
acceptable
chronic
exposure
to
pronamide
in
drinking
water.
The
DWLOC
was
calculated
and
compared
to
the
EECs.
°
The
chronic
DWLOCs
(300
1050
ppb)
were
greater
than
the
EECs
for
modeled
surface
water
(0.53
4.45
ppb),
and
modeled
groundwater
(1.1
ppb).
In
addition,
non
targeted
USGS
monitoring
data
ranged
from
0.0037
to
0.365
ppb
in
surface
water,
and
from
0.005
0.82
ppb
in
ground
water.
The
Agency
concludes
the
chronic
aggregate
risk
estimates
do
not
exceed
the
level
of
concern.
Cancer
Risk
Aggregate
cancer
risk
estimates
will
be
reduced
by
restricting
non
agricultural
uses
to
turf
for
sod
and
seed,
ornamental
landscaping,
industrial
sites,
professional
athletic
fields,
and
golf
courses.
Golfing
is
believed
to
be
a
representative
scenario
for
likely
exposures
to
the
public.
°
The
cancer
risk
estimate
for
golfing
a
single
day
per
year
is
about
the
same
as
the
dietary
cancer
risk
estimate,
or
1
x
10
7
.
After
considering
both
dietary
and
non
dietary
exposure,
the
cancer
DWLOC
is
1.06
ppb.
Without
golf
course
exposure
(i.
e.,
no
recreational
turf
uses
at
all),
the
cancer
DWLOC
would
be
1.2
ppb
based
on
food
exposure
alone.
°
The
Tier
2
PRZM
EXAMS
36
year
mean
EECs
are
0.535
4.35
ppb.
The
modeled
groundwater
EEC
using
SCI
GROW
is
1.1
ppb.
9
°
While
the
modeled
EECs
(4.35
ppb)
are
slightly
higher
than
the
cancer
DWLOC
(1.06
ppb),
the
Agency
is
not
concerned
because
of
the
conservative
inputs
used
in
the
surface
water
modeling.
The
PRZM
EXAMS
assessment
was
based
on
the
maximum
label
rates
for
pronamide,
whereas
typical
rates
for
many
crops
are
25%
50%
less.
The
model
also
assumed
a
Percent
Crop
Area
(PCA)
of
87%,
which
is
likely
to
be
an
overestimate
for
the
commodities
being
assessed.
In
addition,
pronamide
data
exists
for
only
one
soil
in
the
aerobic
soil
metabolism
study.
When
aerobic
soil
metabolism
data
is
only
available
in
one
soil,
a
conservative
extrapolation
factor
is
used
which
is
likely
to
contribute
to
overestimating
potential
persistence
and
exposure.
As
a
result,
Dow
AgroSciences
has
agreed
to
conduct
an
aerobic
soil
metabolism
study
(two
additional
soils)
and
an
aerobic
aquatic
metabolism
study
as
confirmatory
data.
°
Further
refinement
of
drinking
water
modeling
estimates
and/
or
targeted
monitoring
of
water
sources
in
high
pronamide
use
areas
would
provide
more
confidence
in
the
risk
assessment.
Additionally,
information
concerning
the
behavior
of
pronamide
following
drinking
water
treatment
regimes
would
also
help
refine
exposure
estimates.
Tolerance
Reassessment
Summary
Pronamide
tolerances
are
established
under
40
CFR
§180.317
(a),
(b)
and
(c).
The
tolerance
expression,
listed
in
(a)
and
(c),
is
in
terms
of
the
combined
residues
of
the
herbicide
propyzamide
and
its
metabolites
(containing
the
3,
5
dichlorobenzoyl
moiety
and
calculated
as
3,
5
dichloro
N
(1,1
dimethyl
2
propynyl)
benzamide).
The
tolerance
expression,
listed
in
(b),
is
in
terms
of
the
parent
only.
The
Agency
recommends
that
the
tolerance
expression
under
(b)
be
modified
to
include
the
metabolites.
The
Agency
also
recommends
the
following:
decreasing
the
established
tolerance
for
artichokes;
increasing
the
tolerances
for
cattle
fat,
goat
fat,
hog
fat,
horse
fat,
and
sheep
fat,
revoking
the
tolerance
for
poultry
kidney,
grass,
forage:
and,
proposing
a
tolerance
for
alfalfa
seed.
The
Table
below
summarizes
EPA's
tolerance
reassessment
decision
which
accounts
for
47
tolerance
reassessments.
The
Codex
Commission
has
established
several
maximum
residue
limits
(MRLs)
for
residues
of
pronamide
in/
on
various
raw
agricultural
and
processed
commodities.
The
Codex
MRLs
are
expressed
in
terms
of
pronamide
per
se.
The
Codex
MRLs
and
the
U.
S.
tolerances
will
be
incompatible
when
the
U.
S.
tolerance
expression
for
plant
commodities
is
revised
to
include
residues
of
pronamide
and
the
metabolites.
10
Tolerance
Reassessment
Summary
for
Pronamide
Commodity
Established
Tolerance
(ppm)
Reassessed
Tolerance
(ppm)
Comment
Correct
Commodity
definition
Tolerances
Listed
Under
40
CFR
§180.317(
a)
Apples
0.1
0.
1
Artichokes
0.1
0.
01
Residues
of
pronamide
and
its
metabolites
containing
the
3,5
dichlorobenzoyl
moiety
were
nondetectable
(less
than
the
level
of
concern
(LOC)
of
0.01ppm)
in/
on
each
sample
of
artichokes
harvested
61
days
following
a
single
application
of
a
representative
pronamide
formulation
at
4.0
or
8.0
lb
ai/
A.
Blackberries
0.05
0.05
Blueberries
0.05
0.05
Boysenberries
0.05
0.05
Cattle,
fat
0.02
0.20
Fat
tolerance
raised
due
to
linear
extrapolation
of
maximum
residues
observed
in
fat
at
40
ppm
feeding
level
relative
to
the
Maximum
theoretical
dietary
burdens
(MTDB)
Cattle,
kidney
0.
4
0.4
Cattle,
liver
0.4
0.
4
Cattle,
mbyp
(except
kidney,
liver)
0.
02
0.
02
Cattle,
meat
0.02
0.02
Eggs
0.02
0.02
Endive
(escarole)
1.0
1.
0
Goats,
fat
0.02
0.20
Fat
tolerance
raised
due
to
linear
extrapolation
of
maximum
residues
observed
in
fat
at
40
ppm
feeding
level
relative
to
the
MTDB
Goats,
kidney
0.4
0.
4
Goats,
liver
0.4
0.
4
Goats,
mbyp
(except
kidney,
liver)
0.
02
0.
02
Goats,
meat
0.02
0.02
Grapes
0.1
0.
1
Hogs,
fat
0.
02
0.
20
Fat
tolerance
raised
due
to
linear
extrapolation
of
maximum
residues
observed
in
fat
at
40
ppm
feeding
level
relative
to
the
MTDB
Hogs,
kidney
0.
4
0.4
Hogs,
liver
0.4
0.
4
Hogs,
mbyp
(except
kidney)
0.02
0.02
Hogs,
meat
0.02
0.02
Horses,
fat
0.
02
0.
20
Fat
tolerance
raised
due
to
linear
extrapolation
of
maximum
residues
observed
in
fat
at
40
ppm
feeding
level
relative
to
the
MTDB
Commodity
Established
Tolerance
(ppm)
Reassessed
Tolerance
(ppm)
Comment
Correct
Commodity
definition
11
Horses,
kidney
0.
4
0.4
Horses,
liver
0.4
0.
4
Horses,
mbyp
(except
kidney)
0.02
0.02
Horses,
meat
0.02
0.02
Lettuce
1.0
1.
0
Lettuce
Head
Only
head
lettuce
is
supported
by
acceptable
data;
leaf
lettuce
uses
must
be
removed
from
the
label.
Alternatively,
the
label
may
be
revised
to
specify
a
practical
PHI
(35
day)
for
leaf
lettuce
and
supporting
data
be
submitted.
Milk
0.02
0.02
Non
grass
animal
feeds
10.0
10.0
Non
grass
animal
feeds
(forage,
fodder,
straw,
and
hay)
group
Pears
0.
1
0.1
Poultry,
fat
0.
02
0.
02
Poultry,
kidney
0.
2
Revoke
Tolerances
are
typically
not
established
for
poultry
kidneys.
Poultry,
liver
0.2
0.
2
Poultry,
mbyp
(except
kidney,
liver)
0.02
0.02
Poultry,
meat
0.02
0.02
Radicchio,
greens
(tops)
2.
0
2.0
Raspberries
0.05
0.05
Sheep,
fat
0.
02
0.
20
Fat
tolerance
raised
due
to
linear
extrapolation
of
maximum
residues
observed
in
fat
at
40
ppm
feeding
level
relative
to
the
MTDB
Sheep,
kidney
0.
4
0.4
Sheep,
liver
0.4
0.
4
Sheep,
mbyp
(except
kidney,
liver)
0.02
0.02
Sheep,
meat
0.02
0.02
Stone
fruit
0.1
0.
1
Commodity
Established
Tolerance
(ppm)
Reassessed
Tolerance
(ppm)
Comment
Correct
Commodity
definition
12
Tolerances
To
Be
Proposed
Under
40
CFR
§180.317(
a)
Alfalfa
Seed
10.0
Tolerance
recommendation
is
contingent
upon
required
label
revision
to
specify
a
50
day
PHI
and
a
maximum
seasonal
rate
of
2.0
lb
ai/
A
Tolerances
Listed
Under
40
CFR
§180.317(
b)
Cranberries
0.05
Temporary
tolerance
associated
with
a
FIFRA
section
18
that
will
expire
12/
31/
03.
Grass,
forage
1.0
Tolerance
expired
12//
31/
01.
Tolerances
Listed
Under
40
CFR
§180.317(
c)
Peas,
dried
0.
05
TBD
Pea,
field,
seed.
European
data
currently
used
to
support
tolerance.
Registrant
needs
to
submit
field
trial
data
as
confirmatory
data.
Rhubarb
0.1
0.
1
Tolerances
To
Be
Proposed
Under
40
CFR
§180.317(
c)
Pea,
field,
hay
–
TBD
Pea,
field
vines
–
TBD
*TBD=
To
Be
Determined
Summary
of
Pending
Data
Most
pertinent
product
chemistry
data
requirements
are
satisfied
for
technical
grade
active
ingredients.
The
following
information
is
required:
°
Product
Chemistry
GDLN
Description
860.1200
Direction
for
use
860.1380
Storage
Stability
Data
°
Additional
data
are
also
required
for
the
51%
Formulation
Intermediate
(FI)
concerning
the
following:
GDLN
Description
830.6314
oxidation/
reduction
830.6316
explodability
830.6317
storage
stability
830.6320
corrosion
characteristics
13
The
registrant
must
either
certify
that
the
supplier
of
beginning
materials
and
the
manufacturing
processes
have
not
changed
since
the
last
comprehensive
product
chemistry
reviews
or
submit
complete
updated
product
chemistry
data
packages.
Although
there
is
confidence
in
the
overall
scientific
quality
of
the
available
toxicity
data,
several
data
gaps
were
identified
which
are
required
to
fulfill
the
OPPTS
harmonized
test
guidelines:
°
Toxicity
GDLN
Description
870.3700
Developmental
study
in
rats
Non
GDLN
Comparative
thyroid
rat
assay
in
adult
animals
and
offspring
870.3200
21
day
dermal
toxicity
study
Non
GDLN
28
day
inhalation
study
870.7600
dermal
penetration
study
A
review
of
registered
uses
and
the
supporting
residue
chemistry
data
indicates
the
following
residue
data
are
required:
°
Residue
(GDLN
860.1500
Crop
Field
Trials)
dried
winter
peas
vines
and
hay
of
winter
peas
°
Confirmatory
storage
stability
data
(GDLN
860.1380)
are
required
for
regulated
pronamide
metabolites
on
the
following:
alfalfa
apples
grapes
lettuce
peaches
plums
°
A
confirmatory
aerobic
soil
metabolism
study
(835.4100)
and
an
aerobic
aquatic
metabolism
study
(835.4300)
are
required.
The
registrant
is
required
to
further
optimize/
improve
the
revised
animal
enforcement
method
(TR
34
91
68)
to
yield
acceptable
recoveries
at
a
fortification
level
equal
to
established
animal
tolerances.
Following
method
improvement,
the
registrant
is
required
to
submit
bridging
independent
laboratory
validation
(ILV)
data;
the
required
ILV
data
should
include
two
control
samples
fortified
at
0.4
ppm,
the
reassessed
tolerance
level
for
the
kidney
and
liver
of
ruminants.
14
°
The
following
label
amendments
are
required
for
lettuce,
peas,
and
alfalfa
grown
for
seed:
GDLN
Description
860.1850
Confined
Accumulation
in
Rotational
Crops
860.1900
Field
Accumulation
in
Rotational
Crops
°
30
day
plant
back
interval
for
leafy
vegetables
(except
Brassica
vegetables)
°
90
day
plant
back
interval
for
root
and
tuber
vegetables
°
360
day
plant
back
interval
for
cereal
grains,
forage
and
fodder,
and
straw
of
cereal
grain
| epa | 2024-06-07T20:31:42.765359 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0159-0012/content.txt"
} |
EPA-HQ-OPP-2002-0159-0013 | Supporting & Related Material | "2002-07-12T04:00:00" | null | Summary
of
Pronamide
Uses
°
Pronamide
is
a
restricted
use
pesticide.
°
It
is
a
selective,
pre
emergence
herbicide
registered
for
the
control
of
grassy
and
broadleaf
weeds
on
terrestrial
food
crops
[artichoke,
blackberry,
blueberry,
boysenberry,
cherry,
endive
(escarole),
lettuce,
nectarine,
peach,
pear,
plum,
prune,
raspberry,
(black,
red),
rhubarb];
terrestrial
food
and
feed
crops
(agricultural
fallow/
idleland,
apples,
grapes,
peas,
sugar
beets);
terrestrial
nonfood
crops
(Christmas
tree
plantations,
golf
course
turf,
ornamental
herbaceous
plants,
recreation
area
lawns,
and
outdoor
residential
(ornamental
and/
shade
trees,
ornamental
woody
shrubs
and
vines).
Health
Effects
°
Pronamide
is
a
liver
toxicant.
Other
target
organs
include
thyroid,
testes,
kidney,
adrenal
gland,
thymus,
heart,
and
brain.
°
Pronamide
was
previously
classified
as
a
Group
B2
chemical,
probable
human
carcinogen
based
on
thyroid
follicular
cell
adenomas
(male
and
female)
and
benign
interstitial
cell
tumors
(males)
in
rats
and
heptacelluar
carcinomas
in
male
mice.
°
Carcinogenicity
studies
in
rodents
indicate
two
types
of
tumors,
benign
testicular
interstitial
cell
tumors
and
uncommon
thyroid
follicular
cell
adenomas;
and
one
type
of
tumor
in
the
mouse,
hepatocellular
carcinomas.
°
The
cancer
potency
estimate
for
pronamide
using
the
Q1*
model
is
2.59
x
10
2
(mg/
kg/
day)
1
.
FQPA
Safety
Factor
°
A
3x
FQPA
Safety
Factor
is
required
for
all
population
subgroups
when
assessing
non
occupational
exposures
of
all
durations.
Dietary
Food
Risk
°
No
appropriate
toxicologic
endpoint
was
identified
for
acute
dietary
exposure.
Consequently
an
acute
dietary
risk
assessment
was
not
performed
for
pronamide.
°
Chronic
dietary
risk
estimates
from
exposure
to
food
do
not
exceed
the
Agency's
level
of
concern.
The
chronic
dietary
risk
estimate
is
<1%
of
the
cPAD,
for
U.
S.
population
and
for
all
subgroups.
°
The
cancer
dietary
risk
estimate
is
1.06
x
10
7
for
the
U.
S.
population,
and
does
not
exceed
the
Agency's
level
of
concern
(1.0
x
10
6
or
one
in
one
million).
Residential
Risk
°
Registrant
has
voluntarily
cancelled
the
residential
use
product.
°
The
registrant
has
agreed
to
limit
use
to
turf
grown
for
seed
or
sod
and
non
residential
sites
including
golf
courses,
industrial
and
office
building
sites,
stadium
fields
or
professional
athletic
fields.
These
risk
mitigation
measures
make
children's
non
dietary
exposure
unlikely.
To
minimize
adult
non
occupational
exposure,
the
registrant
has
agreed
to
amend
pronamide
labels
to
require
a
24
hour
restricted
entry
interval
or
require
watering
in
as
soon
as
possible
after
application.
°
As
a
result
of
the
risk
assessment,
the
sole
exposure
scenario
for
the
non
occupational
risk
assessment
is
based
on
low
contact
activity
which
is
represented
and
estimated
by
golf
course
reentry.
The
route
of
exposure
is
dermal.
The
population
at
risk
is
adults.
°
The
short
term
Margin
of
Exposure
(MOE)
for
golf
course
reentry
using
zero
day
after
treatment
(DAT
0)
turf
transferable
residue
data
from
the
turf
study
is
1000.
Therefore,
the
Agency
is
not
concerned
about
short
term
residential
exposure
to
pronamide.
°
No
intermediate
or
long
term
exposure
scenarios
(i.
e.,
greater
than
30
days)
are
anticipated
based
on
the
results
of
the
turf
transferable
residue
(TTR)
study
which
showed
that
residues
dissipate
to
below
the
level
of
quantification
by
day
14
following
application.
°
The
adult
golfer
cancer
risk
is
estimated
at
1.15
x
10
7
.
In
order
to
exceed
the
cancer
risk
(1.0
x
10
6
),
an
exposure
frequency
of
8.7
days
per
year
would
be
needed
for
the
activity
of
golf.
Because
pronamide
is
applied
one
time
per
year,
the
Agency
does
not
believe
this
exposure
frequency
will
occur.
Therefore,
the
cancer
risk
for
golfers
does
not
exceed
the
Agency's
level
of
concern.
Drinking
Water
Assessment
°
Short
term
and
chronic
drinking
water
exposure
to
pronamide
did
not
result
in
a
risk
estimate
of
concern
for
non
cancer
risks.
The
short
term
EECs
ranged
between
3.7
to
10.3
ppb,
depending
on
the
crop,
compared
to
the
DWLOC
which
ranges
from
560
to
700
ppb.
The
chronic
non
cancer
EECs
range
between
0.53
to
4.45
ppb,
depending
on
the
crop,
compared
to
the
chronic
DWLOC
which
ranged
between
300
to
1050
ppb.
°
There
are
cancer
risk
estimates
which
slightly
exceed
the
Agency's
level
of
concern.
While
the
modeled
groundwater
EEC
is
1.1
ppb
compared
to
the
cancer
DWLOC
1.06
ppb,
the
modeled
surface
water
EECs
exceed
the
DWLOC
for
some
crops
(the
surface
water
cancer
EECs
range
from
0.54
to
4.3
ppb).
3
Aggregate
Risk
°
Risk
estimates
for
all
pathways
of
exposure
are
not
of
concern
for
pronamide
short
term
exposure
when
pronamide
use
is
restricted
per
the
label
changes
cited
above.
The
chronic
aggregate
risk
estimates
do
not
exceed
the
level
of
concern.
°
The
short
term
food,
water,
and
low
contact
dermal
(golfing)
pronamide
exposures
were
aggregated
in
the
Risk
Assessment,
and
the
estimated
environmental
concentration
(EECs)
for
surface
water
(3.69
to
10.3
ppb)
and
ground
water
(1.1
ppb),
modeled
using
SCI
GROW
and
PRZM
EXAMS
did
not
exceed
the
DWLOC
(range
560
700
ppb).
Therefore,
risk
estimates
for
all
pathways
of
exposure
are
not
of
concern
for
pronamide
short
term
exposure
when
pronamide
use
is
restricted
per
the
label
changes.
°
The
chronic
DWLOCs
(300
1050
ppb)
were
greater
than
the
EECs
for
modeled
surface
water
(0.53
4.45
ppb),
and
modeled
groundwater
(1.1
ppb).
In
addition,
non
targeted
USGS
monitoring
data
ranged
from
0.0037
to
0.365
ppb
in
surface
water,
and
from
0.005
0.82
ppb
in
ground
water.
The
Agency
concludes
the
chronic
aggregate
risk
estimates
do
not
exceed
the
level
of
concern.
°
While
the
modeled
EECs
(4.35
ppb)
are
slightly
higher
than
the
cancer
DWLOC
(1.06
ppb),
the
Agency
is
not
concerned
because
of
the
conservative
inputs
used
in
the
surface
water
modeling.
The
PRZM
EXAMS
assessment
was
based
on
the
maximum
label
rates
for
pronamide,
whereas
typical
rates
for
many
crops
are
25%
50%
less.
The
model
also
assumed
a
Percent
Crop
Area
(PCA)
of
87%,
which
is
likely
to
be
an
overestimate
for
the
commodities
being
assessed.
In
addition,
pronamide
data
exists
for
only
one
soil
in
the
aerobic
soil
metabolism
study.
When
aerobic
soil
metabolism
data
is
only
available
in
one
soil,
a
conservative
extrapolation
factor
is
used
which
is
likely
to
contribute
to
overestimating
potential
persistence
and
exposure.
As
a
result,
Dow
AgroSciences
has
agreed
to
conduct
an
aerobic
soil
metabolism
study
(two
additional
soils)
and
an
aerobic
aquatic
metabolism
study
as
confirmatory
data.
Tolerance
Reassessment
Summary
°
Pronamide
tolerances
are
established
under
40
CFR
§180.317
(a),
(b)
and
(c).
The
tolerance
expression,
listed
in
(a)
and
(c),
is
in
terms
of
the
combined
residues
of
the
residues
of
the
herbicide
propyzamide
and
its
metabolites
(containing
the
3,
5
dichlorobenzoyl
moiety
and
calculated
as
3,
5
dichloro
N
(1,1
dimethyl
2
propynyl)
benzamide).
The
tolerance
expression,
listed
in
(b),
is
in
terms
of
the
parent
only.
The
Agency
recommends
that
the
tolerance
expression
under
(b)
be
modified
to
include
the
metabolites.
The
Agency
also
recommends
the
following:
decreasing
the
established
tolerance
for
artichokes,
increasing
the
tolerances
for
cattle
fat,
goat
fat,
hog
fat,
horse
fat,
and
sheep
fat,
revoking
the
tolerance
for
poultry,
kidney;
grass,
forage
and
proposing
a
tolerance
for
alfalfa
seed.
4
Data
Requirements
Most
pertinent
product
chemistry
data
requirements
are
satisfied
for
technical
grade
active
ingredients.
The
following
information
is
required:
°
Product
Chemistry
GDLN
Description
860.1200
Direction
for
use
860.1380
Storage
Stability
Data
°
Additional
data
are
also
required
for
the
51%
Formulation
Intermediate
(FI)
concerning
the
following:
GDLN
Description
830.6314
oxidation/
reduction
830.6316
explodability
830.6317
storage
stability
830.6320
corrosion
characteristics
The
registrant
must
either
certify
that
the
supplier
of
beginning
materials
and
the
manufacturing
processes
have
not
changed
since
the
last
comprehensive
product
chemistry
reviews
or
submit
complete
updated
product
chemistry
data
packages.
Although
there
is
confidence
in
the
overall
scientific
quality
of
the
available
toxicity
data,
several
data
gaps
were
identified
which
are
required
to
fulfill
the
OPPTS
harmonized
test
guidelines:
°
Toxicity
GDLN
Description
870.3700
developmental
study
in
rats
870.3200
21
day
dermal
toxicity
study
Non
GDLN
28
day
inhalation
study
870.7600
dermal
penetration
study
Non
GDLN
comparative
thyroid
rat
assay
in
adult
animals
and
offspring
A
review
of
product
labels
and
the
supporting
residue
chemistry
data
indicates
the
following
reside,
data
are
required:
°
Residue
(GDLN
860.1500
Crop
Field
Trials)
Description
dried
winter
peas
vines
and
hay
of
winter
peas
5
°
The
following
label
amendments
are
required
for
rotational
crops
lettuce,
peas
(winter),
and
alfalfa
grown
for
seed:
GDLN
Description
860.1850
Confined
Accumulation
in
Rotational
Crops
860.1900
Field
Accumulation
in
Rotational
Crops
°
30
day
plant
back
interval
for
leafy
vegetables
(except
Brassica
vegetables)
°
90
day
plant
back
interval
for
root
and
tuber
vegetables
°
360
day
plant
back
interval
for
cereal
grains,
forage
and
fodder,
and
straw
of
cereal
grain
°
Confirmatory
storage
stability
data
(GDLN
860.1380)
are
required
for
regulated
pronamide
metabolites
on
the
following:
Description
alfalfa
apples
grapes
lettuce
peaches
plums
°
A
confirmatory
aerobic
soil
metabolism
study
(835.4100)
and
the
aerobic
aquatic
metabolism
study
(835.4300).
The
registrant
is
required
to
further
optimize/
improve
the
revised
animal
enforcement
method
(TR
34
91
68)
to
yield
acceptable
recoveries
at
a
fortification
level
equal
to
established
animal
tolerances.
Following
method
improvement,
the
registrant
is
required
to
submit
bridging
independent
laboratory
validation
(ILV)
data;
the
required
ILV
data
should
include
two
control
samples
fortified
at
0.4
ppm,
the
reassessed
tolerance
level
for
the
kidney
and
liver
of
ruminants.
| epa | 2024-06-07T20:31:42.771060 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0159-0013/content.txt"
} |
EPA-HQ-OPP-2002-0159-0016 | Supporting & Related Material | "2002-07-12T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION
PESTICIDES
AND
TOXIC
SUBSTANCES
TXR
Number:
0050338
MEMORANDUM
DATE:
January
21,
2002
SUBJECT:
Pronamide
(Propyzamide):
Report
of
the
Mechanism
of
Toxicity
Assessment
Review
Committee
(MTARC)
Evaluation
of
the
Available
Mechanistic
Information
for
the
Active
Ingredient,
Pronamide.
PC
Code:
101701.
DP
Barcode:
D279550.
Submission
Number:
S597844.
FROM:
Michelle
M.
Centra,
Pharmacologist
Reregistration
Branch
III
Health
Effects
Division
(7509C)
THRU:
Pauline
Wagner,
Co
Chair
Karl
Baetcke,
Co
Chair
Mechanism
of
Toxicity
Science
Assessment
Review
Committee
(MTARC)
Health
Effects
Division
(7509C)
TO:
Jess
Rowland,
Co
Chair
Elizabeth
Doyle,
Co
Chair
Hazard
Identification
Assessment
Review
Committee
(HIARC)
Health
Effects
Division
(7509C)
cc:
Anna
Lowit
MTARC
Secretary
Health
Effects
Division
(7509C)
and
Catherine
Eiden,
Branch
Senior
Scientist
Jose
Morales,
Risk
Assessor
Reregistration
Branch
III
Health
Effects
Division
(7509C)
On
October
23,
2001,
the
Mechanism
of
Toxicity
Assessment
Review
Committee
(MTARC)
met
to
prescreen
the
available
Pronamide
toxicology
data
submitted
in
support
of
a
proposed
threshold
mechanism
for
the
induction
of
thyroid
and
testicular
neoplasms
and
to
determine
whether
a
full
MTARC
review
is
required.
The
Committee's
data
evaluation
and
conclusions
are
presented
in
this
report.
2
Committee
Members
in
Attendance
Members
present
were:
Karl
Baetke,
Karen
Hammernik,
Anna
Lowit
Member(
s)
in
absentia:
Pauline
Wagner
Data
evaluation
prepared
by:
Michelle
M.
Centra,
Reregistration
Branch
III
(RRB
III)
Also
in
attendance
were:
Steve
Knizner
(RRBIII),
Jose
Morales
(RRBIII)
Data
Evaluation
/
Report
Presentation
Michelle
M.
Centra
Pharmacologist
3
Cl
Cl
O
C
CH
3
N
H
CH
CH
3
I.
MTARC
DECISION
Based
on
the
absence
of
any
additional
information
as
well
as
the
MTARC's
evaluation
of
the
existing
pronamide
toxicology
data
base
and
the
Agency's
previous
hazard
characterization
of
this
active
ingredient
(Memorandum:
N.
Thoa,
May
26,
1993),
the
Committee
determined
that
the
postulated
threshold
mechanism
for
the
induction
of
thyroid
and
testicular
neoplasms
remains
incomplete
and
is
not
supported
by
the
available
data.
Therefore,
a
full
Committee
review
for
pronamide
is
not
required.
II.
BACKGROUND
INFORMATION
A.
Introduction
Pronamide
[3,
5
dichloro
N(
1,
1
dimethyl
2
propynyl)
benzamide],
trade
name
Kerb
®
,
is
a
selective,
systemic,
pre
and
post
emergence
herbicide
which
inhibits
root
and
shoot
growth
from
seedlings
and
is
used
to
control
a
wide
range
of
annual
and
perennial
grasses
as
well
as
certain
broadleaf
weeds.
It
is
produced
and
formulated
for
use
as
a
50
W
wettable
powder
in
water
soluble
pouches
(EPA
Reg.
No.
707
159)
by
Rohm
and
Hass
Co.,
Springhouse,
Pennsylvania.
It
is
registered
for
use
in/
on
several
food
and
feed
crops
(alfalfa,
apples,
globe
artichokes,
birdsfoot
trefoil,
blackberries,
blueberries,
cherries,
clover,
crown
vetch,
endive,
grapes,
lettuce,
nectarines,
peaches,
pears,
plums,
prunes,
raspberries,
and
sainfoin).
Pronamide
is
also
registered
for
terrestrial
non
domestic,
non
food
use
on
woody
ornamentals
(azalea,
holly,
juniper,
pine,
rhododendron,
and
yew),
Christmas
trees,
nursery
stocks
(forsythia,
holly,
juniper,
pine,
rhododendron,
and
yew)
and
for
domestic
outdoor
uses
on
lawns,
turfs,
and
fallow
land
to
control
bermudagrass,
centipedegrass,
St.
Augustinegrass,
and
zoysiagrass.
B.
Chemical
Identification
Chemical
Structure:
Empirical
Formula:
C12H11NOCl2
Common
Synonyms:
propyzamide;
3,5
dichloro
N
(1,1
dimethyl
2
propynyl)
benzamide,
Kerb
®
9CI
Name:
23950
58
5
Physical
Properties:
Technical
pronamide
is
a
white
crystalline
solid.
Molecular
Weight:
256.13
Melting
point:
155
156
0
C
Specific
gravity:
0.
48
g/
cc
Water
Solubility:
The
solubility
of
pronamide
in
water
at
25
0
C
is
15
ppm.
4
Pronamide
is
soluble
in
dimethyl
sulfoxide
and
dimethyl
formamide
at
33
ppm;
in
mesityl
oxide,
isophorone,
methyl
ethyl
ketone,
and
cyclohexanone
at
20
ppm;
in
methanol,
isopropanol,
and
chlorobenzene
at
12
15
ppm;
in
butyl
cellosolve,
xylene,
acetonitrile,
and
kerosene
at
10
ppm;
and
in
nitrobenzene
and
ethylene
dichloride
at
5
ppm.
CAS
No.:
23950
58
5
PC
Code:
101701
C.
Toxicity
Summary
Pronamide
appears
to
be
a
liver
toxicant.
Adverse
liver
related
effects
(increases
in
liver
weight
and/
or
liver
related
serum
enzymes
and/
or
histopathology)
were
consistently
observed
in
every
animal
species
studied,
including
the
rat
(subchronic,
chronic,
and
2
generation
reproduction
studies),
mouse
(carcinogenicity
studies),
rabbit
(developmental
study),
and
dog
(subchronic
and
chronic
studies).
Other
target
organs
included
the
thyroid
in
rats
(increase
in
weight
and/
or
histopathology
observed
in
the
chronic
toxicity/
carcinogenicity
and
the
2
generation
reproduction
studies
as
well
as
a
subchronic,
special
13
week
thyroid
function
study),
the
testes
in
rats
(histopathology
in
the
chronic
toxicity/
carcinogenicity
study)
and
the
kidneys,
adrenal
glands
thymus,
heart,
testes,
and
brain
in
dogs
(increase
in
organ
weights
in
the
chronic
toxicity
study),
and
the
pituitary
in
rats
(histopathology
observed
in
the
subchronic
and
2
generation
reproduction
studies).
Many
chemicals
belonging
to
the
class
of
organochlorine
chemicals
are
known
to
produce
disruption
of
the
endocrine
system
1
.
Pronamide
belongs
to
this
class
of
chemicals.
The
Carcinogenicity
Peer
Review
Committee
(CPRC)
classified
Pronamide
as
a
group
B2
probable
human
carcinogen
with
inadequate
evidence
in
humans
(Memorandum:
N.
B.
Thoa
and
E.
Rinde,
May
26,
1993).
This
decision
was
based
on
the
finding
of
two
types
of
tumors
in
the
rat
(benign
testicular
interstitial
cell
tumors
and
uncommon
thyroid
follicular
cell
adenomas),
and
one
type
of
tumor
in
the
mouse
(hepatocellular
carcinomas).
A
linear,
low
dose
approach
(Q1
*)
was
used
for
human
risk
characterization.
The
most
potent
unit
risk
Q1
*,
based
on
male
mouse
liver
adenoma
and/
or
carcinoma
combined
tumor
rates,
is
2.
59
x
10
2
(mg/
kg/
day)
1
in
human
equivalents
[converted
from
animal
to
humans
by
use
of
the
(mg/
kg
body
weight)
3/
4
interspecies
scaling
factor]
(Memorandum:
L.
Brunsman,
October
26,
2001).
In
addition
to
the
required
guideline
toxicity
studies,
two
special
studies
were
conducted
to
evaluate
pronamide's
effect
on
hormonal
balance
in
support
of
a
threshold
mechanism
for
the
induction
of
thyroid
and
testicular
neoplasms.
The
CPRC
also
considered
this
data
in
its
weight
of
evidence
deliberations
and
concluded
the
following:
°
The
data
provided
on
thyroid
mechanism
were
suggestive
of
a
thyroid
pituitary
hormonal
control
mechanism
but
were
not
conclusive,
based
on
the
Agency's
six
criteria
for
a
threshold
model
of
thyroid
neoplasia
(See
Appendix,
Carcinogenicity
Peer
Review
of
Pronamide
3
rd
).
For
example,
there
were
no
dose
related
and/
or
sustained
increases
in
TSH
levels,
no
dose
related
increases
in
incidence
of
thyroid
hypertrophy/
hyperplasia,
and
no
information
on
thyroid
hormone
synthesis.
5
°
The
Agency
has
no
policy
which
implements
a
threshold
model
for
testicular
neoplasia.
Endocrine
function
of
the
testis
may
or
may
not
be
regulated
through
a
feedback
mechanism
similar
to
that
controlling
thyroid
function,
e.
g.
through
an
involvement
of
the
anterior
pituitary.
Even
if
a
testis
pituitary
hormonal
control
mechanism
existed,
the
evidence
supporting
pronamide
induced
testicular
tumors
in
the
rat
via
a
disruption
in
the
testis
pituitary
balance
is
very
limited.
There
was
no
clear
increase
in
interstitial
cell
hypertrophy/
hyperplasia,
no
alteration
in
testosterone
level,
no
information
on
testicular
hormone
synthesis
and
no
reversibility
of
testicular
lesions.
Although
several
endocrine
effects
have
been
observed
in
pronamide
toxicity
studies,
the
data
provided
in
special
studies
conducted
to
explore
potential
mechanisms
of
endocrine
toxicity,
are
incomplete.
Based
on
the
CPRC's
weight
of
evidence
evaluation
of
this
data
base,
it
was
determined
that
even
if
a
hormonal
mechanism
could
be
demonstrated
for
tumors
in
the
rat,
the
mouse
liver
tumors
can
not
be
discounted
(the
Q1
*
is
based
on
the
incidence
of
liver
tumors
in
mice).
Therefore,
a
mechanistic
approach
to
risk
assessment
for
the
active
ingredient
pronamide
is
not
plausible.
1
Hileman,
B.,
March
19,
1993.
Concerns
broaden
over
chlorine
and
chlorinated
hydrocarbons
calls
for
gradual
phaseout
of
classes
of
chlorinated
organics
are
being
made
in
response
to
evidence
of
adverse
health
effects
on
humans
and
wild
life.
C
&
E
News,
volume
71,
No.
16,
pp
11
20.
6
III.
Data
Presentation
A.
Listing
and
Presentation
of
Available
Data
Table
1.
Endocrine/
Other
Effects
Observed
in
Pronamide
Toxicity
Studies
Study
Type
(MRID
Number)
Dose
and
Exposure
Duration
Endocrine
and
Other
Effects
Study
Citation
and
Study
Classification
Chronic
Toxicity/
Car
cinogenicity
Study
Rats
(MRID
41714001,
41714002)
Pronamide
was
administered
to
Crl:
CD(
BR)
VAF/
Plus
Rats
in
the
diet
at
either
0,
25,
100,
or
400
ppm
for
the
first
2
weeks,
followed
by
0,
35,
140,
or
560
ppm
for
the
next
3
weeks
and
thereafter,
0,
40,
200,
or
1000
ppm
(equal
to
0,
1.
73,
8.46,
and
42.59
mg/
kg/
day
for
males
and
0,
2.
13,
10.69,
and
55.09
mg/
kg/
day
for
females,
respectively).
Increased
incidences
of
non
neoplastic
lesions
were
observed
in
the
liver,
thyroid,
and
ovaries
of
high
dose
(1000
ppm)
rats.
In
the
liver,
centrilobular
hypertrophy
was
observed
in
males
and
females
at
12
months
(65%
in
males;
95%
in
females)
and
24
months
(20%
in
males;
48%
in
females).
Hypertrophy
was
accompanied
by
eosinophilic
cell
alteration
at
24months
(positive
trend
in
both
sexes;
pair
wise
comparison
in
high
dose/
controls
for
males
and
females).
In
the
thyroid,
follicular
cell
hypertrophy
was
observed
(positive
trend
in
males
and
in
females)
at
12
months
but
not
at
24
months.
The
increased
incidence
observed
at
1000
ppm
was
only
significant
(pair
wise
comparison
in
high
dose/
controls)
in
females.
At
24
months,
follicular
cell
hyperplasia
was
observed
in
females
(positive
trend)
but
the
increased
incidence
observed
at
1000
ppm
was
not
statistically
significant.
In
the
ovaries,
sertoliform
tubular
hyperplasia
(positive
trend)
was
observed
in
females
at
24
months
and
the
increase
in
incidence
observed
at
1000
ppm
was
significant
by
pair
wise
comparison.
Bailey,
D.
E.
(1990):
Kerb
®
Herbicide
(Technical,
no
clay):
24
Month
Dietary
Chronic
Toxicity/
Oncogenicity
Study
in
Rats;
Hazleton
Laboratories
America,
Inc.
for
Rohm
&
Haas
Co.;
HLA
417
426S,
HLA
417
426M;
November
2,
1990
(Unpublished
Study)
Acceptable
Guideline
Table
1.
Endocrine/
Other
Effects
Observed
in
Pronamide
Toxicity
Studies
Study
Type
(MRID
Number)
Dose
and
Exposure
Duration
Endocrine
and
Other
Effects
Study
Citation
and
Study
Classification
7
Non
Guideline
Endocrine
Study
Male
Rats
(MRID
42093401)
Pronamide
was
administered
to
male
Crl:
CD
®
BR
Rats
in
the
diet
at
concentrations
of
0,
40,
1000
or
4000
ppm
Pronamide
for
either
4
or
15
weeks.
Parameters
of
thyroid
function,
T4
hepatic
metabolism,
and
exogenous
125
I
biliary
clearance
were
investigated,
in
support
of
Pronamide's
thyroid
tumorigenic
mechanism
of
action
involving
disruption
of
the
thyroid
pituitary
hormonal
balance.
At
1000
ppm,
pronamide
treatment
resulted
in
decreased
body
weights
and
food
consumption,
increased
absolute
and/
or
relative
weights
of
the
liver
and
thyroid
(absolute
after
4
weeks;
absolute
and
relative
after
15
weeks),
increased
serum
TSH
(at
4
weeks
but
not
at
13
weeks),
decreased
serum
T4,
and
an
increased
incidence
of
thyroid
and
pituitary
hypertrophy/
hyperplasia.
The
highest
dose
tested
(4000
ppm)
produced
more
profound
effects
on
the
body
weights,
liver
weights
and
serum
T4
than
was
seen
in
the
mid
dose
(1000
ppm).
Pronamide
exposure
resulted
in
increased
thyroid
(relative)
weight
and
increased
incidences
of
thyroid
and
pituitary
hypertrophy/
hyperplasia
which
were
comparable
to
the
mid
dose,
but
did
not
statistically
change
serum
TSH
levels.
Specific
parameters
were
investigated
only
at
the
high
dose:
T4
hepatic
metabolism
and
125
I
biliary
clearance
were
both
increased
and
all
of
the
thyroid
and
liver
related
changes
occurring
after
4
weeks
of
dosing,
were
either
reduced
in
severity
or
absent
11
weeks
following
discontinuation
of
the
dosing.
Based
on
the
six
Agency
criteria
for
thyroid
effects,
there
is
suggestive
evidence
that
the
thyroid
tumors
in
the
rat
associated
with
pronamide
administration
may
result
from
disruption
of
the
thyroid
pituitary
hormonal
balance.
This
evidence
is
weakened
by
the
lack
of
a
dose
related
and
sustained
increase
in
serum
TSH,
and
the
lack
of
a
dose
related
increase
in
the
incidence
of
thyroid
follicular
cell
hypertrophy/
hyperplasia.
There
was
also
no
investigation
of
T4
hepatic
metabolism
and
biliary
clearance
at
the
high
dose
level
(1000
ppm)
which
was
also
a
test
dose
used
in
the
rat
chronic
toxicity/
carcinogenicity
study
that
demonstrated
thyroid
adenomas.
Hazelton,
G.
A.,
Didonato,
L.
J.,
Donofrio,
K.
F,
Kulwich,
B.
A.
(1991):
Pronamide
(Kerb
®
Herbicide):
Thyroid
Function
and
Hepatic
Clearance
of
Thyroxine
inMale
Rats;
Rohm
&
Haas
Co.,
Toxicology
Department
for
Rohm
&
Haas
Co.;
90R
178;
October
9,
1991
(Unpublished
Study)
Acceptable
Nonguideline
Table
1.
Endocrine/
Other
Effects
Observed
in
Pronamide
Toxicity
Studies
Study
Type
(MRID
Number)
Dose
and
Exposure
Duration
Endocrine
and
Other
Effects
Study
Citation
and
Study
Classification
8
Non
Guideline,
Pilot
Endocrine
Study
Male
Rats
(MRID
42139601)
Pronamide
was
administered
to
male
Crl:
CD
®
BR
Rats
in
the
diet
at
concentrations
of
either
0,
or
4000
ppm
for
13
weeks.
Clinical
chemistry
and
histopathological
parameters
of
testicular
function,
as
well
as
hepatic
metabolism
of
testosterone
were
investigated,
to
lend
support
to
Pronamide's
testicular
tumorigenic
mechanism
of
action
involving
disruption
of
the
pituitary
testis
hormonal
balance.
Clinical
chemistry
parameters
were
also
measured
in
male
rats
treated
with
0,
40,
1000,
or
4000
ppm
pronamide
for
4
weeks.
In
the
13
week
study,
pronamide
(4000
ppm)
produced
decreased
body
weight
(weeks
1
13)
and
food
consumption
(weeks
1
8),
increased
serum
LH
and
FSH
levels
(respective
increases
at
4
and
13
weeks
were
60%
and
58%
for
FSH,
and
100%
and
77%
for
LH),
increased
liver
weight
(absolute
and
relative
to
body
and
brain
weight),
microsomal
protein
content,
oxidation
of
testosterone,
activity
of
cytochrome
P450
,
cytochrome
B5,
NADPH
cytochrome
C
reductase,
and
gross
pathology
of
the
liver
(enlarged/
dark),
and
increased
testicular
relative
(to
body)
weight
,
and
testicular
interstitial
cell
hyperplasia.
In
the
4
week
study,
alterations
in
clinical
chemistry
parameters
(increases
in
serum
LH
and
FSH)
were
noted
only
at
4000
ppm
and
were
comparable
to
the
increases
observed
after
13
weeks
of
dosing.
The
most
positive
supporting
evidence
for
the
involvement
of
the
pituitary
in
testicular
neoplasia
is
the
increase
in
serum
LH
and
FSH
levels
after
4
and
15
weeks
of
treatment.
There
was,
however,
no
concomitant
decrease
in
serum
testosterone.
Futhermore,
studies
were
not
conducted
which
may
have
demonstrated
that
this
lack
of
effect
was
produced
by
some
additional
effect
of
pronamide
(e.
g.,
an
increase
in
testosterone
clearance
accompanying
the
moderate
stimulatory
effect
[54%
increase/
g
liver]
on
testosterone
metabolism).
There
also
was
no
evidence
of
testicular
lesion
progression
and/
or
lesion
reversibility.
The
CPRC
concluded
that
this
data
is,
at
best,
incomplete
and
additional
studies
should
be
conducted
in
order
to
support
the
Registrant's
theory
of
a
pronamide
induced
testicular
neoplastic
effect
via
disruption
of
the
pituitary
testis
hormonal
balance.
Hazelton,
G.
A.,
Didonato,
L.
J.,
Donofrio,
K.
F.,
Kulwich,
B.
A.
(1991):
Pronamide
(Kerb
®
Herbicide):
Effects
on
Endocrine
Regulation
of
the
testis
in
Rats
Pilot
Study;
Rohm
&
Haas
Co.,
Toxicology
Department
for
Rohm
&
Haas
Co.;
90R
179;
December
6,
1991
(Unpublished
Study)
Acceptable
Nonguideline
Table
1.
Endocrine/
Other
Effects
Observed
in
Pronamide
Toxicity
Studies
Study
Type
(MRID
Number)
Dose
and
Exposure
Duration
Endocrine
and
Other
Effects
Study
Citation
and
Study
Classification
9
Two
Generation
Reproduction
Study
Rats
(MRID
41540301)
Pronamide
was
administered
to
Crl:
CD
®
BR
Rats
in
the
diet
at
concentrations
of
0,
40,
200
or
1500
ppm
(equal
to
3.1,
16.0
and
120.7
mg/
kg/
day
for
females
and
3.6,
18.0
and
130.1
mg/
kg/
day
for
males
for
the
40,
200
and
1500
ppm
dose
groups,
respectively)
through
2
generations
(one
mating
period
per
generation).
Parental
systemic
effects
were
observed
in
rats
treated
with
1500
ppm
pronamide:
decreased
body
weight
and
feed
consumption
in
both
sexes
and
increased
incidences
of
histopathology
of
the
liver
(centrilobular
hepatocytes
hypertrophy;
both
sexes),
adrenal
glands
(zona
glomerulosa
cellular
hypertrophy;
both
sexes),
thyroid
gland
(follicular
cell
hypertrophy;
females),
and
anterior
pituitary
gland
(cellular
hypertrophy;
males)
in
both
P1
and
P2
generations,
and
increased
incidences
of
uterine
gross
pathology
(black
foci/
serosal
surface)
in
P2
females.
Solomon,
H.
M.,
Brown,
W.
R.
(1990):
Pronamide:
Two
Generation
Reproduction
Study
in
Rats;
Rohm
andHaas
Company,
Toxicology
Department
for
Rohm
and
Haas
Company;
Study
Number:
88P
309;
Report
No.
88R
257;
June
14,
1990
(Unpublished)
Acceptable
Guideline
Table
1.
Endocrine/
Other
Effects
Observed
in
Pronamide
Toxicity
Studies
Study
Type
(MRID
Number)
Dose
and
Exposure
Duration
Endocrine
and
Other
Effects
Study
Citation
and
Study
Classification
10
Subchronic
Toxicity
Study
Rats
(MRID
42669403)
Pronamide
was
administed
to
Crl:
CD
®
BR
Rats
in
the
diet
at
concentrations
of
0,
40,
200,
1000,
or
4000
ppm
(equal
to
0,
2.5,
12.3,
60.0,
and
254.0
mg/
kg/
day
for
males
and
0,
3.1,
15.0,74.6,
and
289.2
mg/
kg/
day
for
females,
respectively)
for
3
months
At
1000
ppm,
pronamide
treatment
resulted
in
increases
in
liver
relative
(to
body)
weight,
and
incidence
of
liver
centrilobular
hypertrophy
in
both
sexes,
decreases
in
body
weight/
weight
gain
and
feed
consumption
in
females,
and
increases
in
blood
cholesterol
levels
in
males.
Additional
toxicities
observed
at
4000
ppm
included
an
increase
in
clinical
signs
(brown
and/
or
yellow
staining
of
the
anogenital
area)
in
males,
decreases
in
body
weight/
weight
gain
and
feed
consumption
in
males
and
further
exacerbation
of
the
later
in
females.
In
addition,
more
pronounced
effects
were
observed
in
the
liver,
thyroid
and
pituitary
at
the
highest
dose
tested:
increases
in
cholesterol
(both
sexes),
SGOT
and
alkaline
phosphatase
(males),
triglycerides
(females),
liver
absolute/
relative
weights
(both
sexes),
incidence/
severity
of
liver
centrilobular
hypertrophy
(both
sexes),
incidence
of
thyroid
follicular
hypertrophy
(both
sexes)
and
anterior
pituitary
cellular
hypertrophy
(males).
The
liver,
thyroid
and
pituitary
appear
to
be
target
organs.
After
4
weeks
of
recovery,
most
of
the
adverse
effects
observed
at
the
high
dose
were
partially
or
totally
reversed
but
the
increase
in
the
incidence
of
pituitary
cellular
hypertrophy
in
males
was
not
diminished.
Anderson,
D.
M.,
Kulwich,
B.
A.,
Hazelton,
G.
A.
(1989):
Pronamide
Technical
(no
clay):
Three
Month
Dietary
Toxicity
Study
in
Rats;
Rohm
&
Haas
Co.
Tox
Dept
for
Rohm
&
Haas
Co.;
Report
No.
88R
053;
September
15,
1989
(Unpublished
Study)
Acceptable
Guideline
Table
1.
Endocrine/
Other
Effects
Observed
in
Pronamide
Toxicity
Studies
Study
Type
(MRID
Number)
Dose
and
Exposure
Duration
Endocrine
and
Other
Effects
Study
Citation
and
Study
Classification
11
Chronic
Toxicity
Study
Dogs
(MRID
41807601,
41807602)
Pronamide
was
administered
to
Beagle
Dogs
in
the
diet
at
concentrations
of
0,
300,
875,
or
1750
ppm
(equal
to
0,
11.9,
33.1,
67.7
mg/
kg/
day
for
males
and
0,
11.9,
36.1,
69.0
mg/
kg/
day
for
females,
respectively)
for
52
weeks.
At
875
ppm,
pronamide
treatment
produced
toxicity
in
several
organs.
In
the
liver,
systemic
toxicity
included
increases
in
serum
alkaline
phosphatase
activity
(males),
increases
in
absolute
and
relative
(to
body)
liver
weight
(males
and
females),
increases
in
the
incidence
of
hepatocytic
hypertrophy/
hyperplasia
and
granular
brown
pigmentation
and
mononuclear
infiltration
of
Kupffer
cells
(males
and
females).
At
1750
ppm,
further
increases
in
serum
alkaline
phosphatase
activity
were
observed
in
both
sexes,
along
with
increases
in
serum
gamma
glutamyl
transferase
(males
and
females)
and
alanine
amino
transferase
activities
(females).
The
incidence/
severity
of
the
histopathologic
alterations
in
the
liver
were
also
exacerbated.
Other
organs
affected
at
1750
ppm
dose
included
the
kidneys
(increase
in
relative
weight
in
females
and
occurrence
of
brown
pigmentation
in
proximal
tubules
in
both
sexes),
thyroid
gland
(increase
in
relative
weight
in
females),
adrenal
glands
(increase
in
relative
weight
in
males
and
absolute/
relative
weights
in
females),
thymus
(increase
in
relative
weight
in
females),
and
heart
and
testes
(increases
in
relative
weights
in
males).
Briffaux,
J.
P.
(1991):
Pronamide
(Kerb
®
Technical
Herbicide):
52
week
oral
(dietary)
toxicity
study
in
the
Beagle
Dog;
Hazleton
France
(HF)
for
Rohm
&
Haas
Co.;
HF
Project
ID
No.
616/
503,
Report
No.
HF
505069,
Rohm
&
Haas
Report
No.:
89RC
110;
February
20,
1991
(Unpublished
Study)
Acceptable
Guideline
12
B.
Data
Evaluation
The
following
data
is
excerpted
from
the
CPRC
document
(Memorandum:
N.
Thoa,
May
26,
1993):
Study
Citation
Bailey,
D.
E.
(1990):
Kerb
®
Herbicide
(Technical,
no
clay):
24
Month
Dietary
Chronic
Toxicity/
Oncogenicity
Study
in
Rats;
Hazleton
Laboratories
America,
Inc.
for
Rohm
&
Haas
Co.;
HLA
417
426S,
HLA
417
426M;
November
2,
1990
(Unpublished
Study);
MRID
Number
41714001
and
41714002.
Increased
incidences
of
non
neoplastic
lesions
were
observed
in
the
liver,
thyroid,
and
ovaries
of
highdose
rats.
In
the
liver,
a
positive
trend
(p
<
0.01)
in
the
incidence
of
centrilobular
hypertrophy
was
observed
in
males
and
females
in
both
phases
(12
and
24
month);
the
increases
observed
at
1000
ppm
were
significant
by
pair
wise
comparison
(p
<
0.01,
both
sexes)
and
appeared
more
pronounced
in
the
12
month
phase
(rate
=
65%
in
males
and
95%
in
females)
than
in
the
24
month
phase
(rate
=
20%
in
males
and
48%
in
females).
Hypertrophy
was
accompanied
by
eosinophilic
cell
alteration
in
the
24month
phase(
p<
0.
01forpositivetrendin
both
sexes;
pair
wisecomparison
in
high
dose/
controls,
p
<
0.
05
in
males
and
p
<
0.
01
in
females).
In
the
thyroid,
a
positive
trend
(p
<
0.
05
in
males
and
p
<
0.
01
in
females)
in
the
incidence
of
follicular
hypertrophy
was
observed
in
the
12
month
phase
but
not
the
24
month
phase.
The
increased
incidence
observed
at
1000
ppm
was
only
significant
(p
<
0.01,
high
dose/
controls)
in
females,
but
the
increased
incidence
observed
at
1000
ppm
was
not
statistically
significant.
In
the
ovaries,
a
positive
trend
(p
<
0.01)
in
the
incidence
of
sertoliform
tubular
hyperplasia
was
observed
in
females
in
the
24
month
phase,
and
the
increase
in
incidence
observed
at
1000
ppm
was
significant
(p
<
0.01)
by
pair
wise
comparison.
Discussion
of
Tumor
Data
At
1000
ppm,
in
the
24
month
phase,
both
male
and
female
rats
had
increased
rates
of
thyroid
follicular
cell
adenomas,
and
male
rats
had
an
increased
incidence
of
benign
testicular
interstitial
cell
tumors.
Thyroid
tumors
were
not
observed
until
weeks
53
and
82
for
males
and
females,
respectively,
and
testicular
tumors
were
not
observed
until
week
67.
The
increase
in
thyroid
tumor
rate
was
statistically
significant
by
pair
wise
comparison
(p
<
0.
01)
only
in
males,
but
there
was
a
positive
trend
(p
<
0.
01)
for
both
sexes.
Both
high
dose
male
and
female
tumor
rates
(21%
and
10%,
respectively)
exceeded
the
historical
control
range
which
was
0
14.8%
(a
mean
value
of
5%
for
males)
and
0
9.
5%
(a
mean
value
of
2%
for
females).
Historical
control
data
for
SD
rats
was
obtained
from
13
studies
conducted
between
1985
and
1990
at
Hazleton
Laboratories,
Vienna,
VA.
There
were
no
significant
differences
in
thyroid
follicular
cell
carcinoma
rates
between
groups.
There
were
increasing
trends
and/
or
rates
in
combined
incidences
of
thyroid
follicular
cell
adenomas
and
carcinomas
(trend
p
<
0.
01
in
males,
p
<
0.
05
in
females;
pair
wise
comparison
of
high
dose
males/
controls,
p
<
0.
05)
which
were
a
reflection
of
the
treatment
related
changes
in
thyroid
follicular
cell
adenoma
rates.
The
increase
in
testicular
interstitial
cell
benign
tumor
rate
was
statistically
significant
by
pair
wise
comparison
(p
<
0.05)
and
there
was
a
positive
trend
(p
<
0.01).
In
high
dose
males,
the
tumor
rate
(27%)
exceeded
the
historical
range
of
4.
8
18.2%
with
a
mean
value
of
5.
6%
(Hazleton
Laboratories,
Vienna,
VA:
historical
control
data
for
SD
rats
obtained
from
11
studies
conducted
between
1985
and
1990).
In
13
the
12
month
phase,
thyroid
follicular
cell
and
testicular
interstitial
cell
neoplasia
were
not
observed
in
any
group.
Benign
pituitary
adenomas
of
the
pars
distalis
were
observed
in
every
dose
group
during
both
the
12
and
24
month
phases,
but
the
tumor
rates
were
statistically
comparable
among
all
groups.
The
respective
tumor
rates
for
the
0,
40,
200,
and
1000
ppm
dose
groups
were
1/
19,
0/
19,
0/
20,
and
3/
20
in
males
and
0/
20,
2/
20,
1/
19,
and
3/
20
in
females
for
the
12
month
phase
and
31/
60,
33/
60,
35/
60,
and
34/
60
in
males
and
49/
60,
49/
60,
49/
60,
and
54/
60
in
females
for
the
24
month
phase.
Adequacy
of
the
Dose
Levels
Tested
The
dosing
was
considered
to
be
adequate
for
assessing
the
carcinogenic
potential
of
Pronamide,
based
on
body
weight
gain
depressions
(p
<
0.05)
of
10%
observed
at
1000
ppm
(weeks
0
26
in
males;
weeks
0
52
in
females).
Feed
consumption
was
also
depressed
(p
<
0.05)
at
1000
ppm
in
males
during
weeks
1
13
(7%),
1
26
(7%),
and
1
52
(5%).
Survival
rate
was
comparable
between
groups.
The
statistical
evaluation
of
mortality
indicates
no
significant
incremental
changes
with
increasing
doses
of
Pronamide
in
either
male
or
female
rats.
Survival
rate
was
comparable
between
groups.
The
statistical
evaluation
of
mortality
indicates
no
significant
incremental
changes
with
increasing
doses
of
pronamide
in
either
male
or
female
rats.
Study
Citation
Hazelton,
G.
A.,
Didonato,
L.
J.,
Donofrio,
K.
F.,
Kulwich,
B.
A.
(1991):
Pronamide
(Kerb
®
Herbicide):
Thyroid
Function
and
Hepatic
Clearance
of
Thyroxine
in
Male
Rats;
Rohm
&
Haas
Co.,
Toxicology
Department
for
Rohm
&
Haas
Co.;
90R
178;
October
9,
1991
(Unpublished
Study);
MRID
Number
42093401.
Histopathology
of
the
Thyroid
Treatment
with
1000
and
4000
ppm
pronamide
for
4
or
15
weeks
was
associated
with
similar
increases
(p
<
0.
05)
in
incidence
of
diffuse
hypertrophy/
hyperplasia
of
the
thyroid
follicular
cells.
There
was
a
positive
trend
after
both
4
and
15
weeks.
The
lesions
were
observed
throughout
the
thyroid
and
were
characterized
by
follicular
cells
with
increased
height,
and
by
follicles
reduced
in
size
and
in
colloid
content.
The
increase
in
incidences
observed
after
4
weeks
of
treatment
with
the
highdose
(10/
10)
was
reduced
(5/
9)
after
the
recovery
period.
The
severity
of
the
lesions
was
greater
at
4000
ppm
than
at
1000
ppm.
Thyroid
Hormone
and
TSH
(4
and
15
week
observations
at
1000
and
4000
ppm
in
male
rats)
Treatment
with
40
4000
ppm
pronamide
for
4
or
15
weeks
was
not
associated
with
any
reduction
in
T3
or
rT3
.T4
was
moderately
reduced
(decreased
at
1000
ppm:
61%
after
4
weeks
and
48%
after
15
weeks;
decreased
at
4000
ppm:
87%
after
4
weeks
and
84%
after
15
weeks).
Except
for
a
moderate
increase
(72%)
observed
after
4
weeks
of
treatment
with
1000
ppm
pronamide,
TSH
remained
unaffected.
The
decrease
in
T4
which
observed
after
4
weeks
of
treatment
with
4000
ppm
pronamide
was
absent
after
11
weeks
of
recovery.
14
T4
Hepatic
Uridine
Diphosphate
Glucuronosyl
Transferase
(UDPGT)
Activity
Treatment
with
4000
ppm
pronamide
for
4
or
15
weeks
was
associated
with
a
2
2.
5
fold
increase
in
UDP
GT
activity
(enzyme
activity
was
expressed
as
nmol
T4
glucuronide
formed/
min/
mg
liver
microsomal
protein).
The
increased
activity
observed
after
4
weeks
of
treatment
with
4000
ppm
pronamide
was
absent
after
11
weeks
of
recovery.
Bile
flow
and
Biliary
Clearance
of
125
I
T4
Treatment
with
4000
ppm
pronamide
for
4
or
15
weeks
was
associated
with
significant
(p
<
0.05)
increases
in
bile
flow
(
65%),
biliary
clearance
of
125
I
T4
(7
10
fold)
and
125
I
T4
glucuronide
(1
2
fold),
and
125
I
bile/
plasma
ratio
after
4
weeks
of
treatment.
The
alterations
in
bile
flow
and
biliary
clearance
were
completely
reversed
after
11
weeks
of
recovery.
Adequacy
of
Dosing
for
Assessment
of
Thyroid
Effects
The
dosing
was
considered
to
be
adequate
for
assessing
the
thyroid
effects
of
pronamide,
based
on
significant
(p
<
0.05)
depressions
of
body
weight
(2
5%
at
1000
ppm,
weeks
1
4;
17
24%
at
4000
ppm,
weeks
1
15)
and
feed
consumption
(4
10%
at
1000
ppm,
weeks
1
4;
11
38%
at
4000
ppm,
weeks
1
15).
Absolute
(abs)
and/
or
relative
(rel)
liver
weight
was
significantly
increased
(p
<
0.
05)
at
1000
ppm,
in
a
dose
related
manner
(4
week
increases:
29%
abs
and
36%
rel
at
1000
ppm,
50%
abs
and
91%
rel
at
4000
ppm;
15
week
increases:
32%
rel
at
1000
ppm;
42%
abs
and
86%
rel
at
4000
ppm).
Thyroid
weight
was
significantly
increased
(p
<
0.
05)
at
1000
ppm
in
a
non
dose
related
manner
(4
week
increases:
29%
abs
and
36%
rel
at
1000
ppm,
32%
rel
at
4000
ppm.
15
week
increases:
21%
rel
at
1000
ppm,
33%
rel
at
4000
ppm).
Study
Citation
Hazelton,
G.
A.,
Didonato,
L.
J.,
Donofrio,
K.
F.,
Kulwich,
B.
A.
(1991):
Pronamide
(Kerb
®
Herbicide):
Effects
on
Endocrine
Regulation
of
the
testis
in
Rats
Pilot
Study;
Rohm
&
Haas
Co.,
Toxicology
Department
for
Rohm
&
Haas
Co.;
90R
179;
December
6,
1991
(Unpublished
Study).
MRID
42139601.
Histopathology
of
the
Testes
Treatment
with
4000
ppm
pronamide
for
13
weeks
was
associated
with
an
increase
in
the
number
of
testicular
interstitial
cells.
The
incidences
were
1/
20
for
the
control
group
and
7/
20
for
the
treated
group.
Interstitial
cells
are
located
between
the
seminiferous
tubules,
normally
in
2
3
cell
focal
clusters
instead
of
layers.
In
this
study,
the
observed
increase
was
determined
to
be
equivocal
because
of
"the
small
degree
of
change
being
evaluated
and
the
possibility
of
producing
this
appearance
through
fortuitous
tangential
sectioning
of
seminiferous
tubules."
The
CPRC
determined
that
this
type
of
sectioning
could
be
seen
in
all
dose
groups.
Clinical
Chemistry
Changes
Treatment
with
4000
ppm
pronamide
for
4
or
13
weeks
was
associated
with
increases
in
serum
LH
and
FSH.
The
increases
were
moderate
and
were
slightly
higher
at
4
weeks
than
at
13
weeks
(respective
increases
at
4
and
13
weeks
were
60%
and
58%
for
FSH,
and
100%
and
77%
for
LH).
Serum
LH
and
FSH
levels
were
not
affected
by
the
mid
level
dose
(1000
ppm).
Serum
testosterone
levels
were
not
affected
by
treatment
with
pronamide.
15
Liver
Microsomal
Enzymes
Activity
Treatment
with
4000
ppm
pronamide
for
13
weeks
increased
the
activity
of
the
liver
microsomal
enzymes
(cytochrome
P450,
cytochrome
B5,
and
NADPH
cytochrome
C
reductase)
and
the
rate
of
oxidation
of
testosterone,
expressed
as
mol
product/
whole
liver.
Concomitant
increases
in
liver
weight
(50%)
and
liver
microsomal
protein
content
(34%)
were
observed,
which
suggests
that
oral
administration
of
relatively
high
doses
of
pronamide
(4000
ppm)
for
a
certain
period
of
time
(13
weeks)
may
result
in
induction
of
the
liver
enzymes
responsible
for
its
metabolism.
Adequacy
of
Dosing
for
Assessment
of
Testicular
Effects
The
dosing
(4000
ppm)
was
considered
to
be
adequate
for
assessing
the
testicular
effects
of
pronamide,
based
on
significant
(p
<
0.05)
depressions
of
body
weight
(14
17%,
weeks
1
13)
and
feed
consumption
(37%,
week
1;
9
12%,
weeks
2
8).
Testicular
relative
(to
body)
weights
were
slightly
increased
(26%;
p
<
0.
05)
and
liver
absolute
and
relative
(to
body)
weights
were
moderately
increased
(59%
absolute;
92%
relative;
p
<
0.
05).
The
liver
related
enzymes,
SGPT
and
SGOT,
were
not
affected
by
treatment
with
pronamide.
IV.
Conclusions
Based
on
an
evaluation
of
the
pronamide
toxicology
data
presented
in
this
report
,
the
MTARC
reaffirmed
the
following
conclusions
of
the
CPRC
(Memorandum:
N.
Thoa,
May
26,
1993):
°
The
postulated
mechanism
of
action
is
at
best
incomplete;
the
Registrant's
postulated
threshold
mechanism
for
the
induction
of
thyroid
and
testicular
neoplasms
is
not
supported
by
the
available
data.
°
Even
if
a
hormonal
mechanism
could
be
demonstrated
for
tumors
in
the
rat,
the
mouse
liver
tumors
can
not
be
discounted
(the
Q1
*
is
based
on
the
incidence
of
liver
tumors
in
mice)
Therefore,
a
mechanistic
approach
to
risk
assessment
for
the
active
ingredient
pronamide
is
not
plausible.
°
Additional
studies
should
be
conducted
to
evaluate
the
potential
for
a
pronamideinduced
thyroid
and
testicular
neoplastic
effect
via
disruption
of
the
pituitary
thyroid
and
pituitary
testis
hormonal
balance,
respectively.
In
the
absence
of
any
additional
data,
the
MTARC
prescreening
committee
determined
that
a
full
MTARC
review
of
the
toxicology
data
base
for
the
active
ingredient
pronamide
is
not
required.
V.
Attachment
(not
available
electronically)
Carcinogenicity
Peer
Review
of
Pronamide
(3rd;
Memorandum:
N.
Thoa,
May
26,
1993)
16
ATTACHMENT
Carcinogenicity
Peer
Review
of
Pronamide
(3rd;
Memorandum:
N.
Thoa,
May
26,
1993)
An
electronic
version
of
this
document
is
not
available.
See
the
hard
copy
file.
| epa | 2024-06-07T20:31:42.774119 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0159-0016/content.txt"
} |
EPA-HQ-OPP-2002-0165-0003 | Supporting & Related Material | "2002-08-12T04:00:00" | null | OPP
Docket
2002
0165
Page
1
of
1
RESPONSE
TO
COMMENTS
Draft
Guidance
on
Submitting
Requests
for
Threshold
of
Regulation
(TOR)
Decisions;
Draft
Standard
Operating
Procedures
(SOP)
for
Making
TOR
Decisions
Comment:
The
American
Chemistry
Council
Biocides
Panel
commented
on
the
TOR
policy
as
it
applies
to
the
use
of
antimicrobial
pesticides.
[Item
004,
OPP
Docket
00795]
Response:
The
policy
issues
raised
in
this
comment
were
not
relevant
to
the
procedural
issues
discussed
in
the
draft
PR
Notice
or
Draft
Standard
Operating
Procedures
for
implementing
the
TOR
policy.
The
comment
was
sent
to
the
Antimicrobials
Division
for
its
consideration.
The
Antimicrobial
Division
will
respond
directly
to
the
commenter.
| epa | 2024-06-07T20:31:42.803993 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0165-0003/content.txt"
} |
EPA-HQ-OPP-2002-0166-0001 | Notice | "2002-08-07T04:00:00" | Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on
Food. | 51260
Federal
Register
/
Vol.
67,
No.
152
/
Wednesday,
August
7,
2002
/
Notices
IV.
Public
Docket
Complete
lists
of
registrations
canceled
for
non
payment
of
the
maintenance
fee
will
also
be
available
for
reference
during
normal
business
hours
in
the
OPP
Public
Docket,
Room
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Highway
South,
Arlington
VA,
and
at
each
EPA
Regional
Office.
Product
specific
status
inquiries
may
be
made
by
telephone
by
calling
toll
free
1
800
444
7255.
List
of
Subjects
Environmental
protection,
Fees.
Dated:
July
25,
2002.
Marcia
E.
Mulkey,
Director,
Office
of
Pesticide
Programs.
[
FR
Doc.
02
19982
Filed
8
6
02;
8:
45
a.
m.]
BILLING
CODE
6560
50
S
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
2002
0166;
FRL
7190
4]
Notice
of
Filing
a
Pesticide
Petition
to
Establish
a
Tolerance
for
a
Certain
Pesticide
Chemical
in
or
on
Food
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.
SUMMARY:
This
notice
announces
the
initial
filing
of
a
pesticide
petition
proposing
the
establishment
of
regulations
for
residues
of
a
certain
pesticide
chemical
in
or
on
various
food
commodities.
DATES:
Comments,
identified
by
docket
ID
number
OPP
2002
0166,
must
be
received
on
or
before
September
6,
2002.
ADDRESSES:
Comments
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
Unit
I.
C.
of
the
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP
2002
0166
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
By
mail:
Treva
Alston,
Registration
Support
Branch,
Registration
Division
(
7505C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(
703)
308
8373;
e
mail
address:
treva.
alston@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
You
may
be
affected
by
this
action
if
you
are
an
agricultural
producer,
food
manufacturer
or
pesticide
manufacturer.
Potentially
affected
categories
and
entities
may
include,
but
are
not
limited
to:
Categories
NAICS
codes
Examples
of
potentially
affected
entities
Industry
111
Crop
production
112
Animal
production
311
Food
manufacturing
32532
Pesticide
manufacturing
This
listing
is
not
intended
to
be
exhaustive,
but
rather
provides
a
guide
for
readers
regarding
entities
likely
to
be
affected
by
this
action.
Other
types
of
entities
not
listed
in
the
table
could
also
be
affected.
The
North
American
Industrial
Classification
System
(
NAICS)
codes
have
been
provided
to
assist
you
and
others
in
determining
whether
or
not
this
action
might
apply
to
certain
entities.
If
you
have
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
this
Document
and
Other
Related
Documents?
1.
Electronically.
You
may
obtain
electronic
copies
of
this
document,
and
certain
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
at
http://
www.
epa.
gov/.
To
access
this
document,
on
the
Home
Page
select
``
Laws
and
Regulations,''
``
Regulations
and
Proposed
Rules,''
and
then
look
up
the
entry
for
this
document
under
the
``
Federal
Register
Environmental
Documents.''
You
can
also
go
directly
to
the
Federal
Register
listings
at:
http://
www.
epa.
gov/
fedrgstr/.
2.
In
person.
The
Agency
has
established
an
official
record
for
this
action
under
docket
ID
number
OPP
2002
0166.
The
official
record
consists
of
the
documents
specifically
referenced
in
this
action,
any
public
comments
received
during
an
applicable
comment
period,
and
other
information
related
to
this
action,
including
any
information
claimed
as
confidential
business
information
(
CBI).
This
official
record
includes
the
documents
that
are
physically
located
in
the
docket,
as
well
as
the
documents
that
are
referenced
in
those
documents.
The
public
version
of
the
official
record
does
not
include
any
information
claimed
as
CBI.
The
public
version
of
the
official
record,
which
includes
printed,
paper
versions
of
any
electronic
comments
submitted
during
an
applicable
comment
period,
is
available
for
inspection
in
the
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Highway,
Arlington,
VA,
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(
703)
305
5805.
C.
How
and
to
Whom
Do
I
Submit
Comments?
You
may
submit
comments
through
the
mail,
in
person,
or
electronically.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP
2002
0166
in
the
subject
line
on
the
first
page
of
your
response.
1.
By
mail.
Submit
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Information
Resources
and
Services
Division
(
7502C),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460.
2.
In
person
or
by
courier.
Deliver
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Information
Resources
and
Services
Division
(
7502C),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Highway,
Arlington,
VA.
The
PIRIB
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(
703)
305
5805.
3.
Electronically.
You
may
submit
your
comments
electronically
by
e
mail
to:
opp
docket@
epa.
gov,
or
you
can
submit
a
computer
disk
as
described
above.
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
Avoid
the
use
of
special
characters
and
any
form
of
encryption.
Electronic
submissions
will
be
accepted
in
Wordperfect
6.1/
8.0
or
ASCII
file
format.
All
comments
in
electronic
form
must
be
identified
by
docket
ID
number
OPP
2002
0166.
Electronic
comments
may
also
be
filed
online
at
many
Federal
Depository
Libraries.
D.
How
Should
I
Handle
CBI
That
I
Want
to
Submit
to
the
Agency?
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
You
may
claim
information
that
you
submit
to
EPA
in
response
to
this
document
as
CBI
by
marking
any
part
or
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/
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152
/
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August
7,
2002
/
Notices
all
of
that
information
as
CBI.
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
as
CBI
must
be
submitted
for
inclusion
in
the
public
version
of
the
official
record.
Information
not
marked
confidential
will
be
included
in
the
public
version
of
the
official
record
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
CBI,
please
consult
the
person
identified
under
FOR
FURTHER
INFORMATION
CONTACT.
E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?
You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
1.
Explain
your
views
as
clearly
as
possible.
2.
Describe
any
assumptions
that
you
used.
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
your
views.
4.
If
you
estimate
potential
burden
or
costs,
explain
how
you
arrived
at
the
estimate
that
you
provide.
5.
Provide
specific
examples
to
illustrate
your
concerns.
6.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
notice.
7.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
ID
number
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
may
also
provide
the
name,
date,
and
Federal
Register
citation.
II.
What
Action
is
the
Agency
Taking?
EPA
has
received
a
pesticide
petition
as
follows
proposing
the
establishment
and/
or
amendment
of
regulations
for
residues
of
a
certain
pesticide
chemical
in
or
on
various
food
commodities
under
section
408
of
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
21
U.
S.
C.
346a.
EPA
has
determined
that
this
petition
contains
data
or
information
regarding
the
elements
set
forth
in
section
408(
d)(
2);
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
support
granting
of
the
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.
List
of
Subjects
Environmental
protection,
Agricultural
commodities,
Feed
additives,
Food
additives,
Pesticides
and
pests,
Reporting
and
recordkeeping
requirements.
Dated:
July
25,
2002.
Peter
Caukins,
Acting
Director,
Registration
Division,
Office
of
Pesticide
Programs.
Summary
of
Petition
The
petitioner
summary
of
the
pesticide
petition
is
printed
below
as
required
by
section
408(
d)(
3)
of
the
FFDCA.
The
summary
of
the
petition
was
prepared
by
the
petitioner
and
represents
the
view
of
the
petitioner.
EPA
is
publishing
the
petition
summary
verbatim
without
editing
it
in
any
way.
The
petition
summary
announces
the
availability
of
a
description
of
the
analytical
methods
available
to
EPA
for
the
detection
and
measurement
of
the
pesticide
chemical
residues
or
an
explanation
of
why
no
such
method
is
needed.
Akzo
Nobel
Surface
Chemistry
LLC
PP
7E4807
EPA
has
received
a
pesticide
petition
PP
7E4807
from
Akzo
Nobel
Surface
Chemistry
LLC,
300
South
Riverside
Plaza,
Chicago,
IL
60606,
proposing,
pursuant
to
section
408(
d)
of
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
21
U.
S.
C.
346a(
d),
to
amend
40
CFR
part
180.
To
establish
an
exemption
from
the
requirement
of
a
tolerance
for
[
2
ethylhexyl
glucopyranoside]
to
be
applied
to
growing
crops
only.
EPA
has
determined
that
the
petition
contains
data
or
information
regarding
the
elements
set
forth
in
section
408(
d)(
2)
of
the
FFDCA;
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
support
granting
of
the
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.
A.
Residue
Chemistry
1.
Plant
metabolism.
The
plant
metabolism
of
2
ethylhexyl
glucopyranoside
has
not
been
investigated.
However,
due
to
the
structural
similarity,
the
metabolic
pathway
for
2
ethylhexyl
glucopyranoside
is
expected
to
be
similar
to
that
of
other
alkyl
glucosides
which
have
been
previously
granted
an
exemption
from
the
requirement
of
a
tolerance,
and
also
of
those
alkyl
glucosides
of
similar
structure
that
appear
on
EPA's
current
List
4B
Inert
Ingredient
List.
2.
Analytical
method.
The
inert
ingredient,
impurities
and
oligomer
distribution
can
be
analyzed
using
high
temperature
gas
chromatography
with
cold
on
column
injection
after
derivatization
with
silylating
reagents.
Low
levels
of
the
inert
ingredient
can
be
detected
by
HPLC.
3.
Magnitude
of
residues.
Given
the
current
extensive
and
widespread
use
of
structurally
similar
nonionic
surfactants
in
herbicide
formulations,
the
added
use
of
2
ethylhexyl
glucopyranoside
will
not
significantly
contribute
to
the
total
use
volume
of
these
materials.
The
expected
concentration
of
2ethylhexyl
glucopyranoside
when
used
in
an
herbicide
formulation
will
be
much
lower
than
the
concentration
of
any
coformulated
pesticide
active
ingredient.
Therefore,
the
comparable
application
rate,
on
a
grams/
acre
basis
will
be
significantly
lower
than
that
of
any
coformulated
active
ingredient.
It
is
then
reasonable
to
assume
that
any
potential
residues
resulting
from
the
use
of
2
ethylhexyl
glucopyranoside
in
a
pesticide
formulation
would
be
insignificant.
B.
Toxicological
Profile
1.
Acute
toxicity.
The
results
of
acute
toxicity
testing
for
2
ethylhexyl
glucopyranoside
are
as
follows:
Acute
oral
LD50
(
rat)
>
2.0
gram/
kilogram
(
g/
kg);
Acute
dermal
LD50
(
rat)
>
2.38
g/
kg;
moderate
to
severe
eye
irritant
(
rabbit);
non
irritating
to
skin
(
rabbit);
not
a
skin
sensitizer
(
guinea
pig).
2.
Genotoxicty.
2
Ethylhexyl
glucoside
was
negative
in
the
Ames
test,
and
did
not
induce
chromosomal
aberrations
in
human
lymphocytes
cultured
in
vivo.
3.
Reproductive
and
developmental
toxicity.
Although
the
final
report
has
not
yet
been
issued,
the
preliminary
results
from
a
one
generation
reproduction
toxicity
study
with
2
ethylhexyl
glucoside
administered
in
male
and
female
Wistar
rats
are
available.
The
results
indicate
gavage
treatment
of
male
and
female
Wistar
rats
with
2
ethylhexyl
glucoside
at
dose
levels
of
15,
150
or
750
milligram/
kilogram
(
mg/
kg)
body
weight/
day
during
one
generation,
revealed
parental
toxicity
in
animals
receiving
750
mg/
kg
b.
w./
day.
Reproductive
parameters
and
development
of
the
pups
were
not
affected
up
to
750
mg/
kg
b.
w./
day.
Parental
toxicity
consisted
of
affected
mortality,
clinical
signs,
body
weights,
and
food
consumption
for
animals
treated
at
750
mg/
kg
body
weight/
day.
Based
on
the
results
in
this
onegeneration
study,
the
definitive
parental
no
observed
adverse
effect
level
(
NOAEL)
was
established
as
being
150
mg/
kg
body
weight/
day.
The
definitive
reproductive
and
developmental
NOAEL
was
established
as
being
750
mg/
kg
body
weight/
day.
4.
Subchronic
toxicity.
A
28
day
oral
toxicity
study
in
the
rat
was
conducted
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2002
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Notices
on
2
ethylhexyl
glucopyranoside.
The
results
were
that
in
the
rat,
750
mg/
kg/
day
represents
the
no
observed
toxic
effect
level
(
NOTEL)
and
150
mg/
kg/
day
represents
the
no
observed
effect
level
(
NOEL).
5.
Chronic
toxicity.
Based
on
the
NOTEL
and
NOEL
results
of
the
28
day
study
conducted
on
2
ethylhexyl
glucopyranoside,
there
are
no
chronic
health
concerns.
6.
Animal
metabolism.
Animal
metabolism
studies
have
not
been
conducted
on
2
ethylhexyl
glucopyranoside.
However,
structurally
similar
radiolabeled
alkyl
glucopyranosides
were
studied
after
oral
administration
to
mice.
The
results
indicate
that
the
glycosidic
bond
was
rapidly
hydrolyzed
in
the
intestine
and
liver
to
sugars
and
the
parent
alcohol.
The
sugars
and
alcohols
then
entered
the
pathways
of
lipid
and
carbohydrate
metabolism.
7.
Metabolite
toxicology.
The
metabolites
of
2
ethylhexyl
glucopyranoside
are
expected
to
be
the
cleavage
products
at
the
glycosidic
bond,
2
ethylhexanol
and
glucose.
The
toxicity
of
these
two
metabolites
is
well
known.
8.
Endocrine
disruption.
No
evidence
of
endocrine
disruption
was
observed
in
any
of
the
studies
conducted
on
2
ethylhexyl
glucopyranoside,
nor
are
there
any
known
reports
of
any
estrogenic
and
adverse
effects
to
human
population
as
a
result
of
the
use
of
2
ethyhexyl
glucopyranoside.
C.
Aggregate
Exposure
1.
Dietary
exposure.
Based
on
the
metabolism
study
that
indicates
alkyl
glucopyranosides
are
readily
metabolized
in
the
liver
and
intestine
to
glucose
and
the
alcohol,
exposure
to
2
ethylhexyl
glucopyranoside
should
not
pose
a
dietary
risk
under
any
foreseeable
circumstances
to
the
U.
S.
population
including
infants
and
children.
i.
Food.
Exposures
to
2
ethylhexyl
glucopyranoside
due
to
ingestion
of
food
is
not
expected
to
occur.
ii.
Drinking
water.
Exposures
to
2
ethylhexyl
glucopyranoside
due
to
ingestion
of
water
is
not
expected
to
occur.
2.
Non
dietary
exposure.
Structurally
similar
alkyl
glucopyranosides
are
currently
being
used
in
a
number
of
institutional
and
household
cleaning
applications.
These
current
uses
are
expected
to
result
in
significantly
higher
exposures
than
exposure
due
to
the
insignificant
residue
levels
resulting
from
the
use
under
the
proposed
exemption
from
the
requirement
of
a
tolerance
applied
to
growing
crops
only.
D.
Cumulative
Effects.
From
the
results
of
the
tests
conducted
on
2
ethylhexyl
glucopyranoside,
no
evidence
of
any
specific
target
organ
toxicity
has
been
produced.
Therefore,
there
is
no
evidence
of
a
common
mechanism
of
toxicity
with
any
other
substance,
and
there
is
no
reason
to
expect
that
the
use
of
2
ethyhexyl
glucopyranoside
will
contribute
to
any
cumulative
toxicity
resulting
from
exposures
to
other
substances
having
a
common
mechanism
of
toxicity.
E.
Safety
Determination
1.
U.
S.
population.
The
results
of
the
acute,
genotoxic,
subacute
and
developmental
toxicity
studies
conducted
on
2
ethylhexyl
glucopyranoside
indicate
a
relatively
low
order
of
toxicity.
Structurally
similar
alkyl
glucopyranosides
currently
exempted
from
the
requirement
of
a
tolerance,
also
appear
on
EPA's
List
4B
Inert
List.
Therefore,
due
to
the
low
order
of
toxicity
of
2
ethylhexyl
glucopyranoside
and
the
lack
of
known
adverse
human
health
effects
associated
with
this
class
of
chemicals,
the
exemption
from
the
requirement
of
a
tolerance
on
growing
crops
only
is
not
expected
to
result
in
any
new,
or
adverse
effects
to
human
health
or
the
environment.
2.
Infants
and
children.
Exposure
to
2
ethylhexyl
glucopyranosides
to
infants
and
children
is
not
expected
to
occur.
The
substance
will
be
used
as
an
inert
ingredient
at
low
levels
on
growing
crops
only,
and
any
residual
levels
are
expected
to
be
insignificant
and
consistent
with
structurally
similar
alkyl
glucopyranosides
currently
exempted
from
the
requirement
of
a
tolerance.
F.
International
Tolerances
No
codex
maximum
residue
levels
have
been
established
for
2
ethyhexyl
glucopyranoside.
[
FR
Doc.
02
19805
Filed
8
6
02;
8:
45
am]
BILLING
CODE
6560
50
S
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
2002
0151;
FRL
7188
6]
Notice
of
Filing
a
Pesticide
Petition
to
Establish
a
Tolerance
for
a
Certain
Pesticide
Chemical
in
or
on
Food
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.
SUMMARY:
This
notice
announces
the
initial
filing
of
a
pesticide
petition
proposing
the
establishment
of
regulations
for
residues
of
a
certain
pesticide
chemical
in
or
on
various
food
commodities.
DATES:
Comments,
identified
by
docket
ID
number
OPP
2002
0151,
must
be
received
on
or
before
September
6,
2002.
ADDRESSES:
Comments
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
Unit
I.
C.
of
the
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP
2002
0151
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
By
mail:
Sidney
Jackson,
Registration
Division
(
7505C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(
703)
305
7610;
e
mail
address:
jackson.
sidney@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
You
may
be
affected
by
this
action
if
you
are
an
agricultural
producer,
food
manufacturer
or
pesticide
manufacturer.
Potentially
affected
categories
and
entities
may
include,
but
are
not
limited
to:
Categories
NAICS
codes
Examples
of
potentially
affected
entities
Industry
111
Crop
production
112
Animal
production
311
Food
manufacturing
32532
Pesticide
manufacturing
This
listing
is
not
intended
to
be
exhaustive,
but
rather
provides
a
guide
for
readers
regarding
entities
likely
to
be
affected
by
this
action.
Other
types
of
entities
not
listed
in
the
table
could
also
be
affected.
The
North
American
Industrial
Classification
System
(
NAICS)
codes
have
been
provided
to
assist
you
and
others
in
determining
whether
or
not
this
action
might
apply
to
certain
entities.
If
you
have
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
VerDate
Aug<
2,>
2002
19:
43
Aug
06,
2002
Jkt
197001
PO
00000
Frm
00102
Fmt
4703
Sfmt
4703
E:\
FR\
FM\
07AUN1.
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pfrm17
PsN:
07AUN1
| epa | 2024-06-07T20:31:42.806879 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0166-0001/content.txt"
} |
EPA-HQ-OPP-2002-0180-0001 | Notice | "2002-09-18T04:00:00" | Chlorpropham Tolerance Reassessment Decision; Notice of Availability.
| <
PRE>
[
Federal
Register:
September
18,
2002
(
Volume
67,
Number
181)]
[
Notices]
[
Page
58795
58797]
From
the
Federal
Register
Online
via
GPO
Access
[
wais.
access.
gpo.
gov]
[
DOCID:
fr18se02
77]
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
2002
0180;
FRL
7198
7]
Chlorpropham
Tolerance
Reassessment
Decision;
Notice
of
Availability
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.
SUMMARY:
This
notice
constitutes
the
Agency's
report
on
the
Food
Quality
Protection
Act
(
FQPA)
tolerance
reassessment
progress
and
risk
management
decision
for
chlorpropham,
announces
the
Agency's
decision,
and
releases
the
human
health
risk
assessment
and
related
documents
supporting
this
decision
to
the
public.
This
notice
of
tolerance
reassessment
for
chlorpropham
starts
the
30
day
public
comment
period
during
which
the
public
is
invited
to
submit
comments
on
the
Agency's
``
Report
of
the
FQPA
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
(
TRED)''
for
chlorpropham.
If
any
comment
causes
the
Agency
to
revise
its
decision
on
tolerance
reassessment
for
chlorpropham,
the
Agency
will
publish
a
notice
of
its
amendment
in
the
Federal
Register.
The
Agency's
reassessment
of
dietary
risk,
including
public
exposure
through
food
and
drinking
water
as
required
by
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
as
amended
by
FQPA,
indicate
that
dietary
risk
from
stored
potatoes
treated
with
chlorpropham
per
se,
poses
no
risk
concerns
within
the
limits
of
the
reassessed
tolerances
associated
with
chlorpropham
use
on
potatoes.
DATES:
Comments
must
be
submitted
on
or
before
October
18,
2002.
ADDRESSES:
Comments
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP
2002
0180
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
Gary
Mullins,
Special
Review
and
Reregistration
Division
(
7508C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(
703)
308
8044;
e
mail
address:
<
A
HREF="
mailto:
mullins.
gary@
epa.
gov">
mullins.
gary@
epa.
gov</
A>.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
This
action
is
directed
to
the
public
in
general.
This
action
may,
however,
be
of
interest
to
those
persons
who
are
or
may
be
required
to
conduct
testing
of
chemical
substances
under
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA)
or
the
FFDCA.
Since
other
entities
may
also
be
interested,
the
Agency
has
not
attempted
to
describe
all
the
specific
entities
that
may
be
affected
by
this
action.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
this
Document
and
Other
Related
Documents?
1.
Electronically.
You
may
obtain
electronic
copies
of
this
document,
and
certain
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
at
<
A
HREF="
http://
frwebgate.
acc
ess.
gpo.
gov/
cgi
bin/
leaving.
cgi?
from=
leavingFR.
html&
log=
linklog&
to=
http://
www.
ep
a.
gov/">
http://
www.
epa.
gov/</
A>.
To
access
this
document,
on
the
Home
Page
select
``
Laws
and
Regulations,''
``
Regulations
and
Proposed
Rules,''
and
then
look
up
[[
Page
58796]]
the
entry
for
this
document
under
the
``
Federal
Register
Environmental
Documents.''
You
can
also
go
directly
to
the
Federal
Register
listings
at
<
A
HREF="
http://
frwebgate.
access.
gpo.
gov/
cgi
bin/
leaving.
cgi?
from=
leavingFR.
h
tml&
log=
linklog&
to=
http://
www.
epa.
gov/
fedrgstr/">
http://
www.
epa.
gov/
fedrgstr/</
A
>.
To
access
TRED
documents
electronically,
go
directly
to
the
TREDs
table
on
the
EPA
Office
of
Pesticide
Programs
Home
Page,
at
<
A
HREF="
http://
frwe
bgate.
access.
gpo.
gov/
cgi
bin/
leaving.
cgi?
from=
leavingFR.
html&
log=
linklog&
to=
http
://
www.
epa.
gov/
pesticides/
reregistration/
status.
htm">
http://
www.
epa.
gov/
pesticides/
reregistration/
status.
htm</
A>.
2.
In
person.
The
Agency
has
established
an
official
record
for
this
action
under
docket
ID
number
OPP
2002
0180.
The
official
record
consists
of
the
documents
specifically
referenced
in
this
action,
any
public
comments
received
during
an
applicable
comment
period,
and
other
information
related
to
this
action,
including
any
information
claimed
as
Confidential
Business
Information
(
CBI).
This
official
record
includes
the
documents
that
are
physically
located
in
the
docket,
as
well
as
the
documents
that
are
referenced
in
those
documents.
The
public
version
of
the
official
record
does
not
include
any
information
claimed
as
CBI.
The
public
version
of
the
official
record,
which
includes
printed,
paper
versions
of
any
electronic
comments
submitted
during
an
applicable
comment
period,
is
available
for
inspection
in
the
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Rm.
119,
Crystal
Mall
<
greek
i>
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(
703)
305
5805.
C.
How
and
to
Whom
Do
I
Submit
Comments?
You
may
submit
comments
through
the
mail,
in
person,
or
electronically.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP
2002
0180
in
the
subject
line
on
the
first
page
of
your
response.
1.
By
mail.
Submit
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Information
Resources
and
Services
Division
(
7502C),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460.
2.
In
person
or
by
courier.
Deliver
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Information
Resources
and
Services
Division
(
7502C),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
Rm.
119,
Crystal
Mall
<
greek
i>
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA.
The
PIRIB
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(
703)
305
5805.
3.
Electronically.
You
may
submit
your
comments
electronically
by
e
mail
to:
<
A
HREF="
mailto:
opp
docket@
epa.
gov">
opp
docket@
epa.
gov</
A>,
or
you
ca
n
submit
a
computer
disk
as
described
above.
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
Avoid
the
use
of
special
characters
and
any
form
of
encryption.
Electronic
submissions
will
be
accepted
in
WordPerfect
6.1/
8.0/
9.0
or
ASCII
file
format.
All
comments
in
electronic
form
must
be
identified
by
docket
ID
number
OPP
2002
0180.
Electronic
comments
may
also
be
<
strong>
filed</
strong>
online
at
many
Federal
Depository
Libraries.
D.
How
Should
I
Handle
CBI
that
I
Want
to
Submit
to
the
Agency?
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
You
may
claim
information
that
you
submit
to
EPA
in
response
to
this
document
as
CBI
by
marking
any
part
or
all
of
that
information
as
CBI.
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
as
CBI
must
be
submitted
for
inclusion
in
the
public
version
of
the
official
record.
Information
not
marked
confidential
will
be
included
in
the
public
version
of
the
official
record
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
CBI,
please
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?
You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
1.
Explain
your
views
as
clearly
as
possible.
2.
Describe
any
assumptions
that
you
used.
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
your
views.
4.
If
you
estimate
potential
burden
or
costs,
explain
how
you
arrived
at
the
estimate
that
you
provide.
5.
Provide
specific
examples
to
illustrate
your
concerns.
6.
Offer
alternative
ways
to
improve
the
notice
or
collection
activity.
7.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
notice.
8.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
ID
number
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
may
also
provide
the
name,
date,
and
Federal
Register
citation.
II.
Background
A.
What
Action
is
the
Agency
Taking?
This
notice
constitutes
and
announces
the
availability
of
the
chlorpropham
TRED.
This
decision
has
been
developed
as
part
of
the
public
participation
process
that
EPA
and
the
U.
S.
Department
of
Agriculture
(
USDA)
are
using
to
involve
the
public
in
the
reassessment
of
pesticide
tolerances
under
FFDCA.
EPA
must
review
tolerances
and
tolerance
exemptions
that
were
in
effect
when
FQPA
was
enacted
in
August
1996,
to
ensure
that
these
existing
pesticide
residue
limits
for
food
and
feed
commodities
meet
the
safety
standard
of
the
new
law.
In
reviewing
these
tolerances,
the
Agency
must
consider,
among
other
things,
aggregate
risks
from
non
occupational
sources
of
pesticide
exposure,
whether
there
is
increased
susceptibility
to
infants
and
children,
and
the
cumulative
effects
of
pesticides
with
a
common
mechanism
of
toxicity.
The
tolerances
are
considered
reassessed
once
the
safety
finding
has
been
made
that
aggregate
risks
are
not
of
concern.
A
reregistration
eligibility
decision
(
RED)
was
completed
for
chlorpropham
in
April
1995,
prior
to
FQPA
enactment,
and
therefore
needed
an
updated
assessment
to
consider
the
provisions
of
the
Act.
The
FQPA
requires
that
the
Agency
consider
``
available
information''
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
``
other
substances
that
have
a
common
mechanism
of
toxicity.''
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
EPA
did
not
perform
a
cumulative
risk
assessment
as
part
of
this
reregistration
review
of
chlorpropham,
because
the
Agency
has
not
determined
if
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
chlorpropham.
If
EPA
identifies
other
substances
that
share
a
common
mechanism
of
toxicity
with
chlorpropham,
then
a
cumulative
risk
assessment
will
be
conducted
that
includes
chlorpropham.
Further,
EPA
is
in
the
process
of
developing
criteria
for
characterizing
and
testing
endocrine
disrupting
chemicals
and
plans
to
implement
an
Endocrine
Disruptor
[[
Page
58797]]
Screening
Program.
Chlorpropham
will
be
reevaluated
at
that
time
and
additional
studies
may
be
required.
Additionally,
the
Agency
has
evaluated
the
dietary
risk
associated
with
chlorpropham
and
has
determined
that
provided
the
Special
Local
Need
(
SLN)
registration
for
Easter
lily
bulb
use
is
amended
to
reduce
the
maximum
rate
of
application
from
3.99
pounds
active
ingredient/
acre
to
2.0
pounds
active
ingredient/
acre,
as
agreed
upon
by
stakeholders,
there
is
a
reasonable
certainty
that
no
harm
to
any
population
subgroup
will
result
from
aggregate
exposure
to
chlorpropham
when
considering
dietary
exposure
and
all
other
non
occupational
sources
of
pesticide
exposure
for
which
there
is
reliable
information.
Therefore,
with
this
mitigation
measure
in
place,
15
tolerances
are
now
considered
reassessed
and
9
new
tolerances
will
be
established
for
residues
of
chlorpropham
in/
on
raw
agricultural
commodities
under
section
408(
q)
of
the
FFDCA.
All
registrants
of
pesticide
products
containing
the
active
ingredient
listed
in
this
document
have
been
sent
the
appropriate
TRED
document,
and
must
respond
to
labeling
requirements
within
8
months
of
receipt.
In
addition,
the
Agency
requests
a
response
to
the
generic
Data
Call
In
(
DCI)
letter
from
technical
registrants
within
90
days
of
receipt.
The
reregistration
program
is
being
conducted
under
Congressionally
mandated
time
frames,
and
EPA
recognizes
both
the
need
to
make
timely
reregistration
decisions
and
to
involve
the
public.
All
comments
received
within
30
days
of
publication
of
this
Federal
Register
notice
will
be
considered
by
the
Agency.
If
any
comment
significantly
impacts
this
TRED,
the
Agency
will
amend
its
decision
by
publishing
a
Federal
Register
notice.
B.
What
is
the
Agency's
Authority
for
Taking
this
Action?
The
legal
authority
for
this
TRED
falls
under
FIFRA,
as
amended
in
1988
and
1996.
Section
4(
g)(
2)(
A)
of
FIFRA
directs
that,
after
submission
of
all
data
concerning
a
pesticide
active
ingredient,
``
the
Administrator
shall
determine
whether
pesticides
containing
such
active
ingredient
are
eligible
for
reregistration,''
and
either
reregistering
products
or
taking
``
other
appropriate
regulatory
action.''
List
of
Subjects
Environmental
protection,
Pesticides,
Tolerances.
Dated:
September
10,
2002.
Lois
A.
Rossi,
Director,
Special
Review
and
Reregistration
Division,
Office
of
Pesticide
Programs.
[
FR
Doc.
<
strong>
02</
strong><
strong>
23593</
strong>
<
strong>
Filed</
strong>
9
17
<
strong>
02</
strong>;
8:
45
am]
BILLING
CODE
6560
50
S
</
PRE>
| epa | 2024-06-07T20:31:42.818826 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0180-0001/content.txt"
} |
EPA-HQ-OPP-2002-0180-0020 | Supporting & Related Material | "2002-12-09T05:00:00" | null | 1
United
States
Prevention,
Pesticides
November
2002
Environmental
Protection
and
Toxic
Substances
EPA
738
F
02
015
Agency
(
7508C)
Chlorpropham
TRED
Facts
EPA
has
assessed
the
risks
of
chlorpropham
and
completed
a
Report
of
the
Food
Quality
Protection
Act
(
FQPA)
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
(
known
as
a
TRED)
for
this
pesticide.
Provided
that
risk
mitigation
measures
are
adopted,
as
outlined
in
the
TRED,
individual
and
aggregated
risks
are
within
acceptable
levels.
The
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
as
amended
by
FQPA,
requires
EPA
to
review
all
the
tolerances
(
legal
limits
for
residues
in
food)
for
registered
chemicals
in
effect
on
or
before
the
date
of
the
enactment
of
the
FQPA.
In
reviewing
these
tolerances,
the
Agency
must
consider,
among
other
things,
aggregate
risks
from
non
occupational
sources
of
pesticide
exposure,
whether
there
is
increased
susceptibility
to
infants
and
children,
and
the
cumulative
effects
of
pesticides
with
a
common
mechanism
of
toxicity.
The
tolerances
are
considered
reassessed
once
the
safety
finding
has
been
made
or
a
revocation
occurs.
EPA
completed
a
chlorpropham
reregistration
eligibility
decision
(
RED)
prior
to
FQPA
of
1996
enactment;
therefore,
tolerances
needed
to
be
reassessed
to
meet
the
FQPA
standard.
The
Agency
has
evaluated
the
dietary
(
food
and
drinking
water)
risk
associated
with
chlorpropham
and
has
determined
that
provided
the
Special
Local
Need
registration
(
SLN)
for
Easter
lily
bulb
use
is
amended
to
reduce
the
maximum
rate
of
application
as
agreed
upon
by
stakeholders,
there
is
a
reasonable
certainty
that
no
harm
to
any
population
subgroup
will
result
from
aggregate
exposure
to
chlorpropham
when
considering
dietary
exposure
and
all
non
occupational
sources
of
pesticide
exposure.
Therefore,
with
the
implementation
of
this
mitigation
measure,
fifteen
(
15)
tolerances
established
for
residues
of
chlorpropham
in/
on
raw
agricultural
commodities
are
now
considered
reassessed
as
safe
under
section
408(
q)
of
the
FFDCA.
Uses
°
Chlorpropham
is
a
herbicide
primarily
registered
for
use
on
post
harvest
potatoes
for
sprout
control.
There
are
four
SLN
registrations
for
use
of
Easter
lilies
(
on
approximately
150
acres
annually
in
Oregon
and
California);
gingko
trees
in
the
District
of
Columbia;
and
post
harvest
potatoes
stored
in
high
humidity
conditions
in
the
state
of
Maine,
which
requires
a
higher
application
rate.
°
Approximately
445,600
pounds
of
chlorpropham
active
ingredient
(
a.
i.)
are
used
annually.
2
Health
Effects
°
Parent
chlorpropham
has
been
classified
by
the
Agency
as
a
"
Group
E"
human
carcinogen
(
no
evidence
of
carcinogenicity).
However,
some
chlorpropham
is
metabolized
to
3
chloroaniline
(
3
CA)
on
potatoes
and
some
anilines
are
known
carcinogens.
The
Agency
does
not
have
data
on
3
CA
necessary
to
conduct
a
carcinogenicity
assessment,
but
does
have
data
for
4
chloroaniline
(
4
CA),
which
is
structurally
similar,
but
not
expected
to
be
formed
in
the
breakdown
of
chlorpropham
in
potatoes.
The
cancer
potency
factor
(
or
Q
1*)
for
4
CA
was
used
as
a
surrogate
to
assess
the
potential
cancer
risk
from
3
CA
and
is
expected
to
overestimate
potential
cancer
risk.
°
There
is
no
evidence
of
endocrine
disruption
from
exposure
to
chlorpropham.
Dietary
(
Food
and
Drinking
Water)
Risks
°
Acute
and
chronic
(
non
cancer
and
cancer)
dietary
exposures
from
eating
food
crops
treated
with
chlorpropham
are
not
of
concern
for
the
entire
U.
S.
population
and
all
subgroups
that
were
assessed.
°
Acute
and
chronic
(
non
cancer)
exposure
through
surface
and
ground
water
sources
of
drinking
water
is
negligible,
and
not
of
concern
to
the
Agency.
However,
there
are
risks
of
concern
from
chronic
(
cancer)
exposure
to
chlorpropham
from
ground
water
sources
of
drinking
water
from
the
limited
Easter
lily
bulb
use.
These
risks
are
addressed
through
the
mitigation
measures
described
below.
Occupational
and
Ecological
Risks
°
Occupational
and
ecological
risk
have
not
been
assessed.
Occupational
and
ecological
risk
management
decisions
were
made
as
part
of
the
1996
chlorpropham
registration
eligibility
decision
(
RED).
No
new
data
has
been
received
to
warrant
reconsideration
of
these
risks.
Risk
Mitigation/
Label
Amendments
In
completing
this
TRED,
the
Agency
has
identified
certain
label
amendments
which
need
to
be
implemented
to
mitigate
risks
of
concern
and
ensure
consistency
among
the
labels.
°
To
mitigate
chronic
(
cancer)
food
and
drinking
water
risks
of
concern
from
Easter
lily
bulb
use,
product
labels
need
to
be
amended
to
reduce
the
maximum
application
rate
from
3.99
lb
a.
i.
per
acre
to
2.0
lb
a.
i.
per
acre.
°
For
aerosol
ready
to
use
(
RTU)
products
used
on
stored
potatoes,
the
labels
which
specify
a
maximum
application
rate
of
165%
of
the
typical
rate
(
0.017
lbs
a.
i.
per
1000
lbs
of
potatoes),
need
to
clearly
state
a
total
seasonal
rate
of
0.028
lb
a.
i.
per
1000
pounds
of
potatoes.
For
the
same
product
labels
which
specify
a
maximum
application
rate
of
145%
of
the
typical
rate,
3
product
labels
need
to
clearly
state
a
total
seasonal
rate
that
does
not
exceed
0.025
lbs
a.
i.
per
1000
pounds
of
potatoes.
°
For
Emulsifiable
Concentrate
(
EC)
products,
a
maximum
seasonal
rate
of
0.0104
lb
a.
i.
per
1000
pounds
of
potatoes
needs
to
be
specified.
°
For
entry
into
enclosed
treatment
/
storage
areas
after
application
of
products
heated
above
250
°
F,
handlers
must
wear
a
respirator
with
either
an
organic
vapor
removing
cartridge
with
a
prefilter
approved
for
pesticides,
or
a
canister
approved
for
pesticides.
Tolerance
Reassessment
Decisions
A
total
of
fifteen
(
15)
tolerances
for
chlorpropham
have
been
reassessed.
Thirteen
(
13)
tolerances
are
to
raised,
one
(
1)
tolerance
is
to
be
lowered,
and
one
(
1)
tolerance
is
to
be
revoked.
In
addition,
nine
(
9)
new
tolerances
are
to
be
established
for
residues
in/
on
raw
agricultural
commodities
under
section
408(
q)
of
the
FFDCA.
Availably
of
Supporting
Documents
A
Notice
of
Availability
of
the
chlorpropham
TRED
and
other
supporting
documents,
including
the
risk
assessments
and
response
to
comments,
has
bee
published
in
the
Federal
Register
on
September
18,
2002
(
67
FR
58795).
A
copy
of
the
TRED
and
all
supporting
documents
will
also
be
available
on
the
Agency's
website
at:
http://
www.
epa.
gov/
pesticides/
reregistration/
status.
htm
EPA
has
established
an
official
public
docket
for
this
action
under
docket
ID
number
OPP
2002
0180,
an
electronic
version
of
which
is
available
through
EPA's
electronic
public
docket
and
comment
system,
EPA
Dockets.
You
may
use
EPA
Dockets
at
http://
www.
epa.
gov/
edocket/
to
submit
or
view
public
comments,
access
the
index
listing
of
the
contents
of
the
official
public
docket,
and
to
access
those
documents
in
the
public
docket
that
are
available
electronically.
Additionally,
you
may
still
access
any
of
the
publicly
available
docket
materials
through
the
OPP
docket
facility.
Once
in
the
system,
select
"
search,"
then
key
in
the
appropriate
docket
ID
number.
| epa | 2024-06-07T20:31:42.823341 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0180-0020/content.txt"
} |
EPA-HQ-OPP-2002-0182-0001 | Notice | "2002-08-21T04:00:00" | Guidance for Developing & Performing Quality Control of Water Modeling Standard Scenarios and
Standard Scenario Metadata Files; Notice of Availability. | 54206
Federal
Register
/
Vol.
67,
No.
162
/
Wednesday,
August
21,
2002
/
Notices
Pennsylvania
Avenue,
NW.,
Washington,
DC
20460.
Telephone:
202Ð
564Ð
3261;
fax:
202Ð
565Ð
0050.
Correction
In
the
Federal
Register
of
August
14,
2002,
in
FR
Doc.
02Ð
20581,
on
page
53001,
in
the
first
column,
correct
the
ADDRESSES
caption
to
read:
ADDRESSES:
The
document
is
available
electronically
through
the
NCEA
Web
site
at
(www.
epa.
gov/
ncea)
under
the
Publications
menus.
A
limited
number
of
paper
copies
will
be
available
from
EPA's
National
Service
Center
for
Environmental
Publications
(NSCEP),
P.
O.
Box
42419,
Cincinnati,
Ohio
45242;
telephone:
1Ð
800Ð
490Ð
9198
or
513Ð
489Ð
8190;
facsimile:
513Ð
489Ð
8695.
Please
provide
your
name
and
mailing
address
and
the
title
and
EPA
number
of
the
requested
publication.
Dated:
August
16,
2002.
Art
Payne,
Acting
Director,
National
Center
for
Environmental
Assessment.
[FR
Doc.
02Ð
21425
Filed
8Ð
20Ð
02;
8:
45
am]
BILLING
CODE
6560–
50–
P
ENVIRONMENTAL
PROTECTION
AGENCY
[OPP–
2002–
0182;
FRL–
7193–
5]
Guidance
for
Developing
and
Performing
Quality
Control
of
Water
Modeling
Standard
Scenarios
and
Standard
Scenario
Metadata
Files;
Notice
of
Availability
AGENCY:
Environmental
Protection
Agency
(EPA).
ACTION:
Notice.
SUMMARY:
EPA
is
soliciting
comments
on
two
documents,
``
PRZM
Field
and
Orchard
Crop
Scenario
Metadata''
and
``
Standard
Procedures
for
Conducting
Quality
Control
and
Quality
Assurance
for
Pesticide
Root
Zone
Model
(PRZM)
Field
and
Orchard
Crop
Scenarios.
''
Interested
parties
may
request
a
copy
of
the
draft
proposed
procedures
and
scenario
documentation
as
a
set
in
Unit
I.
B.
of
this
notice.
The
PRZM
Field
and
Orchard
Crop
Scenario
Metadata
documents
the
crop
specific
parameters
(specific
value
used
and
its
reference)
which
are
key
elements
of
the
exposure
scenario
used
to
determine
surface
water
concentrations
in
ecological
and
drinking
water
assessments.
Standard
Procedures
for
Conducting
Quality
Control
and
Quality
Assurance
for
PRZM
Field
and
Orchard
Crop
Scenarios
provides
a
defined
set
of
steps
(methods
of
selecting
or
estimating
specific
scenario
values
and
available
references)
to
develop
and/
or
ensure
the
quality
of
a
crop
scenario.
Both
documents
provide
a
transparent
description
of
each
environmental
modeling
scenario
and
the
procedures
used
to
create
them
while
providing
consistent
and
reproducible
products.
DATES:
Comments,
identified
by
docket
ID
number
OPPÐ
2002Ð
0182,
must
be
received
on
or
before
October
21,
2002.
ADDRESSES:
Comments
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPPÐ
2002Ð
0182
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
Sid
Abel,
Environmental
Fate
and
Effects
Division
(7507C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(703)
305Ð
7346;
fax
number:
(703)
305Ð
6309;
e
mail
address:
abel.
sid@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
This
action
is
directed
to
the
public
in
general.
This
action
may,
however,
be
of
interest
to
those
who
are
or
may
be
conducting
surface
water
modeling
assessments
on
behalf
of
pesticide
registration,
risk
assessments
or
those
who
may
be
involved
in
developing
information
directly
related
to
data
necessary
to
develop
a
modeling
scenario.
Since
other
entities
may
also
be
interested,
the
Agency
has
not
attempted
to
describe
all
the
specific
entities
that
may
be
affected
by
this
action.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
this
Document
and
Other
Related
Documents?
1.
Electronically.
You
may
obtain
electronic
copies
of
these
documents,
and
certain
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
at
http://
www.
epa.
gov/.
To
access
this
document,
on
the
Home
Page
select
``
Laws
and
Regulations,
''
``
Regulations
and
Proposed
Rules,
''
and
then
look
up
the
entry
for
this
document
under
the
``
Federal
RegisterÑ
Environmental
Documents.
''
You
can
also
go
directly
to
the
Federal
Register
listings
at
http://
www.
epa.
gov/
fedrgstr/.
To
access
information
about
Standard
Procedures
for
Conducting
Quality
Control
and
Quality
Assurance
for
Pesticide
Root
Zone
Model
(PRZM)
Field
and
Orchard
Crop
Scenarios
and
PRZM
Field
and
Orchard
Crop
Scenario
Metadata,
go
directly
to
the
Home
Page
for
the
Office
of
Pesticide
Programs
at:
http://
www.
epa.
gov/
oppefed1/
models/
water/
op
scenario
metadata
df
061602.
htm
and
http://
www.
epa.
gov/
oppefed1/
models/
water/
qa
qc
documentation
ver2
.htm
2.
By
mail.
You
may
obtain
copies
of
these
documents,
and
certain
other
related
documents
that
might
be
available
by
contacting
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
C.
How
and
to
Whom
Do
I
Submit
Comments?
You
may
submit
comments
through
the
mail,
in
person,
or
electronically.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPPÐ
2002Ð
0182
in
the
subject
line
on
the
first
page
of
your
response.
1.
By
mail.
Submit
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Information
Resources
and
Services
Division
(7502C),
Office
of
Pesticide
Programs
(OPP),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460.
2.
In
person
or
by
courier.
Deliver
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Information
Resources
and
Services
Division
(7502C),
Office
of
Pesticide
Programs
(OPP),
Environmental
Protection
Agency,
Rm.
119,
Crystal
Mall
#2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA.
The
PIRIB
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(703)
305Ð
5805.
3.
Electronically.
You
may
submit
your
comments
electronically
by
e
mail
to:
opp
docket@
epa.
gov,
or
you
can
submit
a
computer
disk
as
described
in
this
unit.
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
Avoid
the
use
of
special
characters
and
any
form
of
encryption.
Electronic
submissions
will
be
accepted
in
WordPerfect
6.1/
8.0
or
ASCII
file
format.
All
comments
in
electronic
form
must
be
identified
by
docket
ID
number
OPPÐ
2002Ð
0182.
Electronic
comments
may
also
be
filed
online
at
many
Federal
Depository
Libraries.
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Federal
Register
/
Vol.
67,
No.
162
/
Wednesday,
August
21,
2002
/
Notices
D.
How
Should
I
Handle
CBI
that
I
Want
to
Submit
to
the
Agency?
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
You
may
claim
information
that
you
submit
to
EPA
in
response
to
this
document
as
CBI
by
marking
any
part
or
all
of
that
information
as
CBI.
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
as
CBI
must
be
submitted
for
inclusion
in
the
public
version
of
the
official
record.
Information
not
marked
confidential
will
be
included
in
the
public
version
of
the
official
record
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
CBI,
please
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?
You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
1.
Explain
your
views
as
clearly
as
possible.
2.
Describe
any
assumptions
that
you
used.
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
your
views.
4.
If
you
estimate
potential
burden
or
costs,
explain
how
you
arrived
at
the
estimate
that
you
provide.
5.
Provide
specific
examples
to
illustrate
your
concerns.
6.
Offer
alternative
ways
to
improve
the
notice
or
collection
activity.
7.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
notice.
8.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
ID
number
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
may
also
provide
the
name,
date,
and
Federal
Register
citation.
II.
What
Action
is
the
Agency
Taking?
The
Agency
is
seeking
comment
on
two
documents
that
describe
how
EPA
develops
and
uses
pesticide
surface
water
modeling
scenarios
in
ecological
and
drinking
water
exposure
and
risk
assessments.
These
documents
are
entitled
``
Pesticide
Root
Zone
Model
(PRZM)
Field
and
Orchard
Crop
Scenario
Metadata''
and
``
Standard
Procedures
for
Conducting
Quality
Control
and
Quality
Assurance
for
PRZM
Field
and
Orchard
Crop
Scenarios''
and
can
be
found
at
the
following
web
addresses:
http://
www.
epa.
gov/
oppefed1/
models/
water/
op
scenario
metadata
df
061602.
htm
and
http://
www.
epa.
gov/
oppefed1/
models/
water/
qa
qc
documentation
ver2
.htm
Modeling
scenarios
are
defined
as
the
set
of
characteristics
of
the
agricultural
crop
to
which
a
pesticide
may
be
applied
(e.
g.,
cotton)
and
the
field
information
on
which
the
crop
is
actually
grown
(e.
g.,
soils)
that
are
necessary
to
estimate
pesticide
transport
to
surface
water.
The
modeling
sites,
or
scenarios,
the
OPP
uses
to
estimate
environmental
concentrations
in
surface
water
are
documented
in
and
developed
through
the
use
of
these
documents.
These
documents
were
developed
to
support
the
following
activities:
OP
Cumulative
Risk
Assessment,
the
Agency's
Information
Quality
Guideline,
data
quality
guidelines
and
to
improve
environmental
assessments.
The
first
document,
``
PRZM
Field
and
Orchard
Crop
Scenario
Metadata,
''
provides
a
detailed
listing
of
the
parameters
and
associated
values
specific
to
a
crop
and
field
combination
(e.
g.,
a
cotton
field
in
Yazoo
County,
Mississippi).
OPP
evaluated
several
approaches
to
documenting
the
parameters
from
a
modeling
scenario
used
to
estimate
environmental
exposures.
This
format
is
believed
to
provide
the
most
appropriate
means
to
readily
document
and
recall
critical
information
contained
in
a
given
scenario.
Users
of
this
format,
whether
Agency
staff
or
the
public,
will
be
able
to
quickly
document
a
scenario
in
a
consistent
manner
that
meets
quality
standards
implemented
by
the
OPP.
In
addition,
users
who
retrieve
information
or
wish
to
understand
the
content
of
a
crop
field
scenario
for
a
pesticide
assessment
will
be
assured
of
a
standardized
format
which
simplifies
review.
Information
in
this
document
reflects
the
results
of
the
second
document
``
Standard
Procedures
for
Conducting
Quality
Control
and
Quality
Assurance
for
PRZM
Field
and
Orchard
Crop
Scenarios.
''
Standard
Procedures
for
Conducting
Quality
Control
and
Quality
Assurance
for
PRZM
Field
and
Orchard
Crop
Scenarios
describes
the
set
of
procedures,
methods,
and
references
to
``
construct''
or
review
for
consistency
the
information
contained
in
a
cropfield
scenario.
The
steps
and
recommendation
described
in
this
guidance
provide
a
sound
scientific
basis
for
selecting
information
with
relevance
to
what
is
observed
in
an
actual
agricultural
field
such
as
cotton.
The
methodology
is
intended
to
give
the
regulated
community,
decision
makers
and
the
public
confidence
that
assessments
resulting
from
the
use
of
scenarios
representing
an
agricultural
field
reflect
conditions
that
are
likely
to
occur
in
the
``
real
world.
''
Numerous
methods
and
sources
of
credible
scientific
information
are
given
in
this
document
and
are
considered
readily
available
to
the
public
through
voice
contact,
public
information
sources
(e.
g.,
public
libraries)
or
the
world
wide
web.
The
Agency
has
identified
and
described
as
best
possible
information
to
support
this
guidance
and
seeks
comments
on
what
additional
information
would
help
improve
modeling
scenarios.
List
of
Subjects
Environmental
protection,
Environmental
modeling,
Pesticide
Root
Zone
Model,
PRZM,
Surface
water
exposure,
Pesticides,
Crops,
Modeling
Guidance.
Dated:
August
5,
2002.
Sidney
Abel,
III,
Chief,
Environmental
Risk
Branch
I,
Office
of
Pesticide
Programs.
[FR
Doc.
02Ð
20874
Filed
8Ð
20Ð
02;
8:
45
am]
BILLING
CODE
6560–
50–
S
ENVIRONMENTAL
PROTECTION
AGENCY
[FRL–
7264–
3]
Peak
Oil
Superfund
Site;
Notice
of
Proposed
de
Minimis
Settlement
AGENCY:
Environmental
Protection
Agency
(EPA).
ACTION:
Notice
of
proposed
de
minimis
settlement.
SUMMARY:
Under
section
122(
g)(
4)
of
the
Comprehensive
Environmental
Response,
Compensation
and
Liability
Act
(CERCLA),
the
Environmental
Protection
Agency
has
offered
a
de
minimis
settlement
at
the
Peak
Oil
Superfund
Site
(Site)
under
an
Administrative
Order
on
Consent
(AOC)
to
settle
claims
for
past
and
future
response
costs
at
the
Site.
Approximately
263
parties
have
returned
signature
pages
accepting
EPA's
settlement
offer.
For
thirty
(30)
days
following
the
publication
of
this
notice,
EPA
will
receive
written
comments
relating
to
the
settlement.
EPA
may
withdraw
from
or
modify
the
proposed
settlement
should
such
comments
disclose
facts
or
considerations
which
indicate
the
proposed
settlement
is
inappropriate,
improper,
or
inadequate.
Copies
of
the
proposed
settlement
are
available
from:
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| epa | 2024-06-07T20:31:42.827130 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0182-0001/content.txt"
} |
EPA-HQ-OPP-2002-0188-0001 | Notice | "2002-10-23T04:00:00" | Availability of the Risk Assessment on FQPA Tolerance Reassessment Progress of the TRED
Hexazimone | 65118
Federal
Register
/
Vol.
67,
No.
205
/
Wednesday,
October
23,
2002
/
Notices
submitted
by
Roquette
in
its
Lycasin
80/
55
petition
regarding
numerous
studies
relating
to
the
safety
of
the
ingredient,
including
reports
on:
Digestion,
absorption,
distribution
and
excretion;
acute
oral
toxicity,
subchronic
toxicity,
genotoxicity,
reproduction,
biological
tolerance,
human
exposure,
and
laxation
effects.
1.
Acute
toxicity.
The
acute
oral
toxicity
of
HSH
has
been
evaluated.
The
acute
oral
lethal
dose
(LD50)
of
HSH
is
greater
than
10
grams/
kilogram
(g/
kg).
2.
Genotoxicty.
As
stated
in
Roquette's
GRAS
submission
of
Lycasin
80/
55,
HSH
is
nonmutagenic
and
nonclastogenic
in
short
term
in
vivo,
and
in
vitro
studies.
3.
Reproductive
and
developmental
toxicity.
Again
as
noted
in
Roquette's
GRAS
submission
of
Lycasin
80/
55
HSH
products,
when
administered
to
rats
over
3
generations,
produce
no
significant
effects
on
reproduction.
4.
Subchronic
toxicity.
In
Roquette's
GRAS
submission
for
Lycasin
80/
55,
it
is
noted
that
when
administered
orally
to
rats
and
dogs
in
amounts
of
5
g/
kg
to
15
g/
kg
of
body
weight
per
day
for
90
days,
HSH
produced
no
toxicologically
meaningful
effects
which
could
not
be
accounted
for
by
the
presence
of
sorbitol.
The
possible
treatment
related
effects
are
aggregates
in
the
renal
pelvis
of
some
rats,
diarrhea
in
most
dogs,
and
minimal
ectasia
in
the
renule
tubules
of
some
dogs.
5.
Chronic
toxicity.
HSH
is
used
extensively
in
foods.
Grain
Processing
Corporation
is
not
aware
of
any
chronic
toxic
effects
associated
with
this
product.
6.
Animal
metabolism.
The
GRAS
submission
for
Lycasin
80/
55
developed
by
Roquette
Freres
states
that
over
96%
of
HSH
(Lycasin
80/
55)
is
broken
down
by
the
mammalian
digestive
system
into
the
GRAS
substances,
glucose
and
sorbitol,
the
remaining
4%
is
in
the
form
of
maltitol.
One
half
of
the
maltitol
is
excreted
in
the
feces
and
the
majority
of
the
remainder
is
excreted
in
the
urine.
Within
the
first
2
hours
after
oral
administration
of
HSH
(Lycasin
80/
55),
virtually
all
of
the
glucose
to
glucose
bonds
are
broken
down
in
the
digestive
system,
producing
a
resulting
mixture
of
glucose,
sorbitol,
and
maltitol.
Within
7
hours,
95%
of
the
total
maltitol,
is
broken
down
into
glucose
and
sorbitol.
Of
the
remaining
5%
of
maltitol,
2%
is
found
in
the
digestive
tube
and
fecal
contents,
less
than
1%
is
found
in
the
plasma,
and
approximately
1%
is
excreted
in
the
urine.
There
is
no
accumulation
of
maltitol
in
the
plasma,
liver,
kidneys,
or
spleen
of
rats
fed
13.5
g/
kg/
day
of
Lycasin
80/
55
for
10
days
irrespective
of
whether
measurements
are
made
12
hours
or
10
days
after
cessation
of
dosing.
Lycasin
80/
55
at
the
dose
levels
tested,
30
to
180
grams
per
day,
produces
no
significant
variations
in
the
clinical
chemical,
hematological
or
urinary
profile
of
humans
with
the
exception
of
glucose
and
insulin
peaks
which
are
less
than
50%
of
those
produced
by
equivalent
amounts
of
glucose,
and
50
to
90%
of
those
produced
by
sucrose.
The
only
significant
clinical
effects
are
flatulence
and
diarrhea,
which
can
be
accounted
for
by
the
presence
of
free
and
bound
sorbitol.
The
mean
laxative
threshold
in
adult
males
is
approximately
180
grams
per
day,
while
in
females
the
threshold
is
approximately
100
grams
per
day.
In
children,
the
threshold
is
approximately
60
grams
per
day,
about
half
that
of
adults.
7.
Metabolite
toxicology.
None
of
the
metabolites
of
HSH
are
considered
to
be
of
toxicological
significance
for
the
use
of
this
product
as
a
pesticide
inert
ingredient.
8.
Endocrine
disruption.
Grain
Processing
Corporation
is
not
aware
of
any
endocrine
disruption
with
the
use
of
this
product.
C.
Aggregate
Exposure
1.
Dietary
exposure.
This
product
is
already
used
extensively
in
foods.
Studies
have
shown
that
it
is
safe
even
when
consumed
at
levels
of
up
to
100
g/
day.
i.
Food.
As
a
pesticide
inert
ingredient
HSH
will
not
result
in
any
harmful
exposure.
The
proposed
use
will
not
result
in
any
dietary
exposure
beyond
what
is
currently
present
in
commonly
consumed
foods.
ii.
Drinking
water.
There
is
no
anticipated
human
exposure
to
HSH
through
drinking
water.
HSH
is
expected
to
be
degraded
by
soil
microorganisms
to
carbon
dioxide
and
water
before
it
reaches
surface
or
ground
water.
Moreover,
in
water,
HSH
hydrolyses
to
glucose
and
sorbitol.
2.
Non
dietary
exposure.
No
significant
non
dietary
human
exposure
to
HSH
is
anticipated.
D.
Cumulative
Effects
HSH
is
a
widely
used
food
ingredient,
is
readily
digested
by
humans,
and
there
are
no
cumulative
effects.
Except
for
possible
occupational
exposure
of
the
pesticide
mixer/
loader/
applicator,
the
proposed
use
of
HSH
will
not
result
in
the
exposure
of
other
persons.
E.
Safety
Determination
1.
U.
S.
population.
The
proposed
use
of
HSH
does
not
pose
a
safety
concern
for
the
U.
S.
population
due
to
the
nontoxic
nature
of
the
compound
and
the
absence
of
exposure.
2.
Infants
and
children.
Infants
and
children
will
not
be
exposed
to
HSH
from
its
proposed
use
as
a
pesticide
inert
ingredient.
F.
International
Tolerances
Grain
Processing
Corporation
is
unaware
of
any
international
tolerances
for
this
product.
HSH
was
developed
by
a
Swedish
company
in
the
1960's
and
has
been
widely
used
by
the
food
industry
for
many
years,
especially
in
confectionery
products.
Roquette's
petition
indicates
that
Roquette's
Lycasin
products
have
been
approved
for
use
in
food
in
Europe
since
1963,
as
indicated
below.
Country
Year
of
Approval
Sweden
1963
(reaffirmed
in
1975)
Switzerland
1968
Norway
1975
Finland
1975
(reaffirmed
in
1980)
Denmark
1976
[FR
Doc.
02–
26993
Filed
10–
22–
02;
8:
45
am]
BILLING
CODE
6560–
50–
S
ENVIRONMENTAL
PROTECTION
AGENCY
[OPP–
2002–
0188;
FRL–
7199–
7]
Availability
of
the
Risk
Assessments
on
FQPA
Tolerance
Reassessment
Progress
and
Tolerance
Reassessment
Decision
(TRED)
for
Hexazinone
AGENCY:
Environmental
Protection
Agency
(EPA).
ACTION:
Notice.
SUMMARY:
This
notice
announces
the
availability
of
EPA's
tolerance
reassessment
decision
and
related
documents
for
hexazinone
including
the
Hexazinone
Overview,
Hexazinone
Summary,
Hexazinone
Decision
Document
(TRED),
and
supporting
risk
assessment
documents.
EPA
has
reassessed
the
25
tolerances,
or
legal
limits,
for
residues
of
hexazinone
in
or
on
raw
agricultural
commodities.
These
tolerances
are
now
considered
safe
under
the
Federal
Food,
Drug,
and
Cosmetic
Act
(FFDCA),
as
amended
by
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/
Vol.
67,
No.
205
/
Wednesday,
October
23,
2002
/
Notices
the
Food
Quality
Protection
Act
(FQPA)
of
1996.
DATES:
Comments
on
the
tolerance
reassessment
decision
for
hexazinone,
must
be
received
by
EPA
on
or
before
November
22,
2002.
In
the
absence
of
substantive
comments,
the
tolerance
reassessment
decision
will
be
considered
final.
Comments
on
the
human
health
and
ecological
effects
risk
assessments
for
hexazinone,
must
be
received
by
EPA
on
or
before
November
22,
2002.
ADDRESSES:
Comments
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
the
SUPPLEMENTARY
INFORMATION
section.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP–
2002–
0188
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
Dirk
V.
Helder,
Special
Review
and
Reregistration
Division
(7508C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(703)
305–
4610;
email
address:
helder.
dirk@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
This
action
is
directed
to
the
public
in
general,
but
will
be
of
interest
to
a
wide
range
of
stakeholders,
including
environmental,
human
health,
and
agricultural
advocates;
the
chemical
industry;
pesticide
users;
and
members
of
the
public
interested
in
the
use
of
pesticides.
The
Agency
has
not
attempted
to
describe
all
the
persons
or
entities
who
may
be
interested
in
or
affected
by
this
action.
If
you
have
questions
in
this
regard,
consult
the
persons
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
this
Document
and
Other
Related
Documents?
1.Electronically.
You
may
obtain
electronic
copies
of
this
document,
and
certain
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
at
http://
www.
epa.
gov/.
To
access
this
document,
on
the
Home
Page
select
``
Laws
and
Regulations,
''
``
Regulations
and
Proposed
Rules,
''
and
then
look
up
the
entry
for
this
document
under
the
``
Federal
Register—
Environmental
Documents.
''
You
can
also
go
directly
to
the
Federal
Register
listings
at
http://
www.
epa.
gov/
fedrgstr/.
You
can
obtain
copies
of
the
TRED
and
related
documents
discussed
in
this
notice
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
reregistration/
status.
htm.
Information
on
pesticide
reregistration
and
tolerance
reassessment,
including
the
purpose
and
status
of
Agency
programs
to
complete
Reregistration
Eligibility
Decisions
(REDs),
Interim
REDs,
and
Tolerance
Reassessment
Decisions
(TREDs),
is
available
at
http://
www.
epa.
gov/
pesticides/
reregistration.
General
information
is
available
on
the
Office
of
Pesticide
Programs'
home
page,
http://
www.
epa.
gov/
pesticides/.
2.
In
person.
The
Agency
has
established
an
official
record
for
this
action
under
docket
ID
number
OPP–
2002–
0188.
The
official
record
consists
of
the
documents
specifically
referenced
in
this
action,
and
other
information
related
to
this
action,
including
any
information
claimed
as
Confidential
Business
Information
(CBI).
This
official
record
includes
the
documents
that
are
physically
located
in
the
docket,
as
well
as
the
documents
that
are
referenced
in
those
documents.
The
public
version
of
the
official
record
does
not
include
any
information
claimed
as
CBI.
The
public
version
of
the
official
record,
which
includes
printed,
paper
versions
of
any
electronic
comments
submitted
during
an
applicable
comment
period
is
available
for
inspection
in
the
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Rm.
119,
Crystal
Mall
#2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(703)
305–
5805.
C.
How
and
to
Whom
Do
I
Submit
Comments?
You
may
submit
comments
through
the
mail,
in
person,
or
electronically.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP–
2002–
0188
in
the
subject
line
on
the
first
page
of
your
response.
1.
By
mail.
Submit
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Information
Resources
and
Services
Division
(7502C),
Office
of
Pesticide
Programs
(OPP),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460.
2.
In
person
or
by
courier.
Deliver
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Information
Resources
and
Services
Division
(7502C),
Office
of
Pesticide
Programs
(OPP),
Environmental
Protection
Agency,
Rm.
119,
Crystal
Mall
#2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA.
The
PIRIB
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(703)
305–
5805.
3.
Electronically.
You
may
submit
your
comments
electronically
by
e
mail
to:
opp
docket@
epa.
gov,
or
you
can
submit
a
computer
disk
as
described
in
this
unit.
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
Avoid
the
use
of
special
characters
and
any
form
of
encryption.
Electronic
submissions
will
be
accepted
in
WordPerfect
6.1/
8.0/
9.0
or
ASCII
file
format.
All
comments
in
electronic
form
must
be
identified
by
docket
ID
number
OPP–
2002–
0188.
Electronic
comments
may
also
be
filed
online
at
many
Federal
Depository
Libraries.
D.
How
Should
I
Handle
CBI
that
I
Want
to
Submit
to
the
Agency?
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
You
may
claim
information
that
you
submit
to
EPA
in
response
to
this
document
as
CBI
by
marking
any
part
or
all
of
that
information
as
CBI.
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
as
CBI
must
be
submitted
for
inclusion
in
the
public
version
of
the
official
record.
Information
not
marked
confidential
will
be
included
in
the
public
version
of
the
official
record
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
CBI,
please
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?
You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
1.
Explain
your
views
as
clearly
as
possible.
2.
Describe
any
assumptions
that
you
used.
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
your
views.
4.
If
you
estimate
potential
burden
or
costs,
explain
how
you
arrived
at
the
estimate
that
you
provide.
5.
Provide
specific
examples
to
illustrate
your
concerns.
6.
Offer
alternative
ways
to
improve
the
notice
or
collection
activity.
7.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
notice.
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/
Vol.
67,
No.
205
/
Wednesday,
October
23,
2002
/
Notices
8.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
ID
number
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
may
also
provide
the
name,
date,
and
Federal
Register
citation.
II.
What
Action
is
the
Agency
Taking?
EPA
has
reassessed
the
risks
associated
with
current
food
uses
of
the
pesticide
hexazinone,
reassessed
25
existing
tolerances,
and
reached
a
tolerance
reassessment
and
risk
management
decision.
The
Agency
is
issuing
for
comment
the
resulting
report
on
FQPA
tolerance
reassessment
progress,
including
the
Hexazinone
Overview,
Hexazinone
Summary,
Hexazinone
Decision
Document
(TRED),
and
supporting
risk
assessment
documents.
EPA
must
review
tolerances
and
tolerance
exemptions
that
were
in
effect
when
FQPA
was
enacted
in
August
1996,
to
ensure
that
these
existing
pesticide
residue
limits
for
food
and
feed
commodities
meet
the
safety
standard
established
by
the
new
law.
Tolerances
are
considered
reassessed
once
the
safety
finding
has
been
made
or
a
revocation
occurs.
EPA
has
reviewed
and
made
the
requisite
safety
finding
for
the
tolerances
and
exemptions
included
in
this
notice.
EPA
completed
the
hexazinone
Reregistration
Eligibility
Decision
(RED)
prior
to
the
1996
enactment
of
the
FQPA;
therefore,
while
no
reregistration
decision
is
required
at
present,
risks
from
non
occupational
exposure
to
hexazinone
through
food,
drinking
water,
and
residential
uses
must
be
reassessed.
There
are
no
residential
uses
of
hexazinone.
The
Agency
has
reassessed
the
25
tolerances
for
hexazinone
and
determined
that
residues
in
food
and
drinking
water
are
not
expected
to
pose
risk
concerns.
Because
existing
data
were
inadequate
to
calculate
residue
estimates
for
pasture
and
rangeland
grass
and
grass
hay,
EPA
constructed
the
maximum
theoretical
dietary
burden
(MTDB)
of
hexazinone
to
livestock
using
protective
assumptions
for
the
contributions
of
other
hexazinone
treated
feed
items.
Thus,
tolerances
for
meats
and
milk
can
be
reassessed.
Additional
field
trial
data
for
grass
forage
and
grass
hay,
as
well
as
rotational
crop
studies
for
corn
and
wheat
are
required.
Because
of
the
relatively
low
volume
of
use
on
pasture
and
rangeland,
data
from
these
confirmatory
studies
are
not
expected
to
significantly
change
current
dietary
risk
estimates.
Some
tolerances
may
be
revised
once
additional
data
has
been
submitted
to
and
reviewed
by
the
Agency.
The
current
tolerance
expression
for
hexazinone
in
40
CFR
180.396
is
for
``
combined
residues
of
the
herbicide
hexazinone
(3
cyclohexyl
6
(dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione)
and
its
metabolites,
calculated
as
hexazinone.
''
The
tolerance
expression
should
be
modified
to
include
specific
metabolites
A,
B,
C,
D,
and
E,
identified
by
the
appropriate
chemical
name.
Final
tolerances
are
being
proposed
as
part
of
this
Tolerance
Reassessment
Decision
(TRED).
In
addition,
occupational
and
ecological
risk
management
decisions
were
made
as
part
of
the
1994
hexazinone
RED.
EPA
works
with
affected
parties
to
reach
the
tolerance
reassessment
decisions.
The
Agency
therefore
is
issuing
the
hexazinone
decision
as
a
final
decision
with
a
public
comment
period.
All
comments
received
during
the
public
comment
period
will
be
considered
by
the
Agency.
If
any
comment
significantly
affects
the
Agency's
decision,
EPA
will
publish
an
amendment
to
the
decision
in
the
Federal
Register.
In
the
absence
of
substantive
comments,
the
tolerance
reassessment
decisions
reflected
here
will
be
considered
final.
List
of
Subjects
Environmental
protection,
Chemicals,
Pesticides
and
pests.
Dated:
October
4,
2002.
Betty
Shackleford,
Acting
Director,
Special
Review
and
Reregistration
Division,
Office
of
Pesticide
Programs.
[FR
Doc.
02–
26577
Filed
10–
22–
02;
8:
45
am]
BILLING
CODE
6560–
50–
S
ENVIRONMENTAL
PROTECTION
AGENCY
[OPP–
2002–
0223;
FRL–
7274–
1]
Availability
of
the
Report
on
FQPA
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
(TRED)
for
Metolachlor
AGENCY:
Environmental
Protection
Agency
(EPA).
ACTION:
Notice.
SUMMARY:
This
notice
announces
the
availability
of
the
report
on
the
Food
Quality
Protection
Act
(FQPA)
tolerance
reassessment
progress
and
Risk
Management
Decision
(TRED)
for
metolachlor
for
public
comment.
EPA
has
reassessed
the
81
tolerances,
or
legal
limits,
established
for
residues
of
metolachlor
in/
on
raw
agricultural
commodities
(RACs).
These
tolerances
are
now
considered
safe
under
the
Federal
Food,
Drug,
and
Cosmetic
Act
(FFDCA),
as
amended
by
the
FQPA
of
1996.
DATES:
Comments,
identified
by
docket
ID
number
OPP–
2002–
0223,
must
be
received
on
or
before
November
22,
2002.
ADDRESSES:
Comments
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP–
2002–
0223
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
Anne
Overstreet,
Special
Review
and
Reregistration
Division
(7508C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(703)
308–
8068;
fax
number:
(703)
308–
8005;
e
mail
address:
overstreet.
anne@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
This
action
is
directed
to
the
public
in
general,
but
will
be
of
interest
to
a
wide
range
of
stakeholders,
including
environmental,
human
health,
and
agricultural
advocates;
the
chemical
industry;
pesticide
users;
and
members
of
the
public
interested
in
the
use
of
pesticides.
The
Agency
has
not
attempted
to
describe
all
the
persons
or
entities
who
may
be
interested
in
or
affected
by
this
action.
If
you
have
questions
in
this
regard,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
this
Document
and
Other
Related
Documents?
1.
Electronically.
You
may
obtain
electronic
copies
of
this
document,
and
certain
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
at
http://
www.
epa.
gov/.
To
access
this
document,
on
the
Home
Page
select
``
Laws
and
Regulations,
''
``
Regulations
and
Proposed
Rules,
''
and
then
look
up
the
entry
for
this
document
under
the
``
Federal
Register—
Environmental
Documents.
''
You
can
also
go
directly
to
the
Federal
Register
listings
at
http://
www.
epa.
gov/
fedrgstr/.
You
can
obtain
copies
of
the
TRED
and
related
documents
discussed
in
this
notice
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
reregistration/
status.
htm.
VerDate
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| epa | 2024-06-07T20:31:42.832514 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0001/content.txt"
} |
EPA-HQ-OPP-2002-0188-0002 | Supporting & Related Material | "2002-09-16T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
August
1,
2002
CERTIFIED
MAIL
Tom
Stommel
Dupont
Stine
Haskell
Research
Center
PO
Box
30
Newark,
DE
19714
Dear
Mr.
Stommel:
This
is
the
Environmental
Protection
Agency's
(hereafter
referred
to
as
EPA
or
the
Agency)
"Report
of
the
Food
Quality
Protection
Act
(FQPA)
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
(TRED)
for
Hexazinone,"
which
was
approved
on
August
1,
2002.
A
Notice
of
Availability
of
this
tolerance
reassessment
decision
will
be
published
in
the
Federal
Register
(FR)
shortly.
The
Federal
Food,
Drug
and
Cosmetic
Act
(FFDCA),
as
amended
by
FQPA,
requires
EPA
to
reassess
all
the
tolerances
for
registered
chemicals
in
effect
on
or
before
the
date
of
the
enactment
of
the
FQPA,
which
was
August
of
1996.
In
reassessing
these
tolerances,
the
Agency
must
consider,
among
other
things,
aggregate
risks
from
non
occupational
sources
of
pesticide
exposure,
whether
there
is
increased
susceptibility
to
infants
and
children,
and
the
cumulative
effects
of
pesticides
with
a
common
mechanism
of
toxicity.
Once
a
safety
finding
has
been
made
that
aggregate
risks
are
not
of
concern,
the
tolerances
are
considered
reassessed.
A
Reregistration
Eligibility
Decision
(RED)
for
hexazinone
was
completed
in
September,
1994,
prior
to
FQPA
enactment.
Therefore,
the
tolerances
need
to
be
reassessed
to
meet
the
FQPA
standard.
The
Agency
has
evaluated
the
dietary
risk
associated
with
hexazinone
and
has
determined
that
there
is
a
reasonable
certainty
that
no
harm
to
any
population
subgroup
will
result
from
aggregate
exposure
to
hexazinone
when
considering
dietary,
drinking
water,
and
residential
exposure
and
all
other
non
occupational
sources
of
pesticide
exposure
for
which
there
is
reliable
information.
There
are
no
registered
residential
uses
for
hexazinone.
FQPA
requires
that
EPA
consider
"available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"other
substances
that
have
a
common
mechanism
of
toxicity."
The
reason
for
considering
other
substances
is
because
of
the
possibility
that
low
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect,
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
EPA
did
not
perform
a
cumulative
risk
assessment
as
part
of
this
review
of
hexazinone,
2
because
the
Agency
has
not
determined
that
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
hexazinone.
If
EPA
identifies
other
substances
that
share
a
common
mechanism
of
toxicity
with
hexazinone,
then
a
cumulative
risk
assessment
will
be
conducted
that
includes
hexazinone
once
the
final
framework
EPA
will
use
for
conducting
cumulative
risk
assessments
is
available.
Further,
EPA
is
in
the
process
of
developing
criteria
for
characterizing
and
testing
endocrine
disrupting
chemicals
and
plans
to
implement
an
Endocrine
Disruptor
Screening
Program.
Hexazinone
will
be
reevaluated
at
that
time
and
additional
studies
may
be
required.
The
Agency's
human
health
findings
for
the
pesticide
hexazinone,
were
discussed
in
a
closure
conference
call,
and
are
summarized
in
the
enclosed
Hexazinone
Overview
and
Hexazinone
Summary
of
the
risk
assessments.
The
risk
assessments
and
other
documents
pertaining
to
the
hexazinone
tolerance
reassessment
decision
are
available
on
the
Internet
at
http://
www.
epa.
gov/
pesticides/
reregistration/
status.
htm
and
are
in
the
public
docket
for
viewing.
The
Agency
has
reassessed
all
25
tolerances
for
hexazinone
and
can
make
a
FQPA
safety
determination.
Anticipated
residues
for
commodities
included
in
the
dietary
risk
assessment
are
equal
to
the
tolerance
levels
and
it
was
assumed
that
100%
of
each
crop
was
treated.
Acute
and
chronic
dietary
risks
from
exposure
to
hexazinone
does
not
exceed
the
Agency's
level
of
concern.
Tolerances
for
residues
of
hexazinone
in/
on
plant,
livestock,
and
processed
commodities
are
currently
expressed
in
terms
of
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone).
Because
existing
data
were
inadequate
to
calculate
residue
estimates
for
pasture
and
rangeland
grass
and
grass
hay,
EPA
constructed
the
maximum
theoretical
dietary
burden
(MTDB)
of
hexazinone
to
livestock
using
protective
assumptions
for
the
contributions
of
other
hexazinone
treated
feed
items.
Thus,
tolerances
for
meats
and
milk
can
be
reassessed.
Additional
field
trial
data
for
grass
forage
and
grass
hay,
as
well
as
rotational
crop
studies
for
corn
and
wheat
are
required.
Because
of
the
relatively
low
volume
of
use
on
pasture
and
rangeland,
data
from
these
confirmatory
studies
are
not
expected
to
significantly
change
current
dietary
risk
estimates.
Final
tolerances
are
being
proposed
as
part
of
this
Tolerance
Reassessment
Decision
(TRED).
Some
revisions
to
these
tolerance
values
may
be
needed
once
the
field
trial
data
and
rotational
crop
studies
have
been
submitted
to
and
reviewed
by
the
Agency.
Tolerance
Reassessment
Summary
for
Hexazinone.
Commodity
Current
Tolerance
(ppm)
a
Tolerance
Reassessment
(ppm)
Comment/
Correct
Commodity
Definition
Tolerances
presently
listed
under
40
CFR
§180.396(
a):
Alfalfa
green
forage
2.0
2.0
Alfalfa,
forage
Alfalfa
hay
8.0
4.0
Tolerance
should
be
reduced
based
on
re
calculation
of
expected
residues.
Alfalfa,
hay
Blueberries
0.2
0.6
Tolerance
should
be
increased
based
on
the
combined
LOQ
(0.55
ppm)
of
the
enforcement
method.
Blueberry
Commodity
Current
Tolerance
(ppm)
a
Tolerance
Reassessment
(ppm)
Comment/
Correct
Commodity
Definition
3
Cattle,
fat
0.1
Revoke
b
Cattle,
mbyp
0.1
0.1
Cattle,
meat
0.1
0.1
Goat,
fat
0.1
Revoke
b
Goat,
mbyp
0.1
0.1
Goats,
meat
0.1
0.1
Grasses,
pasture
10
TBD
c
Grass,
forage
Grasses,
rangeland
10
TBD
c
Grass,
hay
Hog,
fat
0.1
Revoke
b
Hog,
mbyp
0.1
Revoke
b
Hog,
meat
0.1
Revoke
b
Horses,
fat
0.1
Revoke
b
Horses,
mbyp
0.1
0.1
Horses,
meat
0.1
0.1
Milk
0.5
0.2
Tolerance
should
be
reduced
based
on
re
calculation
of
expected
residues.
Pineapple
0.5
0.6
Tolerance
should
be
increased
based
on
the
combined
LOQ
(0.55
ppm)
of
the
enforcement
method.
Sheep,
fat
0.1
Revoke
b
Sheep,
mbyp
0.1
0.1
Sheep,
meat
0.1
0.1
Tolerances
needed
under
40
CFR
§180.396(
a):
Alfalfa,
seed
2.0
Tolerances
presently
listed
under
40
CFR
§180.396(
c):
Sugarcane
0.2
0.6
Tolerance
should
be
increased
based
on
the
combined
LOQ
(0.55
ppm)
of
the
enforcement
method.
Sugarcane
molasses
5.0
4.0
Tolerance
should
be
reduced
based
on
re
calculation
of
expected
residues.
Commodity
Current
Tolerance
(ppm)
a
Tolerance
Reassessment
(ppm)
Comment/
Correct
Commodity
Definition
4
Sugarcane
molasses
d
5.0
4.0
Tolerance
should
be
reduced
based
on
re
calculation
of
expected
residues.
a
Expressed
in
terms
of
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone).
b
Tolerances
for
fat
are
not
required
(Category
3,
40
CFR
§180.6).
c
TBD:
These
tolerances
require
additional
field
trial
data
and
may
be
revised
once
the
data
have
been
submitted
to
and
reviewed
by
the
Agency.
d
For
reassessment
counting
purposes,
the
Agency
will
count
the
sugarcane
molasses
tolerances
as
two
reassessments
to
reflect
the
tolerances
which
existed
both
in
40
CFR
Part
185
(185.3575)
and
Part
186
(186.3575)
at
the
start
of
FQPA.
No
maximum
residue
limits
(MRLs)
for
hexazinone
and
its
metabolites
have
been
established
or
proposed
by
Codex
for
any
agricultural
commodity.
Therefore,
no
compatibility
questions
exist
with
respect
to
U.
S.
tolerances.
Note
that
you
will
be
sent
a
Section
3(
c)(
2)(
B)
Data
Call
In
(DCI)
letter
under
the
Federal
Insecticide,
Fungicide,
Rodenticide
Act
(FIFRA)
in
a
separate
mailing.
If
you
have
questions
on
this
or
any
of
the
attached
documents,
please
contact
the
Chemical
Review
Manager,
Dirk
V.
Helder,
at
(703)
305
4610.
Sincerely,
Lois
A.
Rossi,
Director
Special
Review
and
Reregistration
Division
Enclosures:
"Hexazinone
Overview"
and
"Hexazinone
Summary"
| epa | 2024-06-07T20:31:42.839211 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0002/content.txt"
} |
EPA-HQ-OPP-2002-0188-0003 | Supporting & Related Material | "2002-09-16T04:00:00" | null | OVERVIEW
OF
HEXAZINONE
RISK
ASSESSMENT
Introduction
This
document
summarizes
EPA's
human
health
findings
and
conclusions
for
the
herbicide
hexazinone,
as
presented
fully
in
the
documents:
HED
Chapter
for
the
Hexazinone
Tolerance
Reassessment
Eligibility
Decision,
dated
June
5,
2002,
and
Tier
I
Estimated
Environmental
Concentrations
of
Hexazinone,
dated
April
16,
2002
and
addenda.
The
purpose
of
this
overview
is
to
assist
the
reader
in
better
understanding
the
conclusions
reached
in
the
tolerance
reassessment
decision
by
identifying
the
key
features
and
findings
of
the
risk
assessment.
This
overview
was
developed
in
response
to
comments
and
requests
from
the
public,
which
indicated
that
the
risk
assessments
were
difficult
to
understand,
that
they
were
too
lengthy,
and
that
it
was
not
easy
to
compare
the
assessments
for
different
chemicals
due
to
the
use
of
different
formats.
The
Federal
Food,
Drug,
and
Cosmetic
Act
(FFDCA),
as
amended
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996,
requires
EPA
to
review
all
the
tolerances
for
registered
chemicals
in
effect
on
or
before
the
date
of
the
enactment
of
FQPA.
In
reviewing
these
tolerances,
the
Agency
must
consider,
among
other
things,
aggregate
risks
from
non
occupational
sources
of
pesticide
exposure,
whether
there
is
increased
susceptibility
to
infants
and
children,
and
the
cumulative
effects
of
pesticides
with
a
common
mechanism
of
toxicity.
The
tolerances
are
considered
reassessed
once
the
safety
finding
has
been
made
or
a
revocation
occurs.
A
Reregistration
Eligibility
Decision
(RED)
for
hexazinone
was
completed
in
September
1994,
prior
to
FQPA
enactment;
therefore,
it
needed
to
be
updated
to
consider
the
provisions
of
the
Act.
FQPA
stipulates
that
when
determining
the
safety
of
a
pesticide
chemical,
EPA
shall
base
its
assessment
of
the
risk
posed
by
the
chemical
on,
among
other
things,
available
information
concerning
the
cumulative
effects
to
human
health
that
may
result
from
dietary,
residential,
or
other
nonoccupational
exposure
to
other
substances
that
have
a
common
mechanism
of
toxicity.
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
substances
individually.
A
person
exposed
to
a
pesticide
at
a
level
that
is
considered
safe
may
in
fact
experience
harm
if
that
person
is
also
exposed
to
other
substances
that
cause
a
common
toxic
effect
by
a
mechanism
common
with
that
of
the
subject
pesticide,
even
if
the
individual
exposure
levels
to
the
other
substances
are
also
considered
safe.
EPA
did
not
perform
a
cumulative
risk
assessment
as
part
of
the
Tolerance
Reassessment
Decision
(TRED)
for
hexazinone
because
the
Agency
has
not
yet
initiated
a
comprehensive
review
to
determine
if
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
hexazinone.
For
purposes
of
this
risk
assessment,
EPA
has
assumed
that
hexazinone
does
not
have
a
common
mechanism
of
toxicity
with
other
substances.
2
In
the
future,
the
registrant
may
be
asked
to
submit,
upon
EPA's
request
and
according
to
a
schedule
determined
by
the
Agency,
such
information
as
the
Agency
directs
to
be
submitted
in
order
to
evaluate
issues
related
to
whether
hexazinone
shares
a
common
mechanism
of
toxicity
with
any
other
substance
and,
if
so,
whether
any
tolerances
for
hexazinone
need
to
be
modified
or
revoked.
The
Agency
has
developed
a
framework
for
conducting
cumulative
risk
assessments
on
substances
that
have
a
common
mechanism
of
toxicity.
This
guidance
was
issued
on
January
16,
2002
(67
FR
2210
2214)
and
is
available
from
the
OPP
Website
at:
http://
www.
epa.
gov/
pesticides/
trac/
science/
cumulative_
guidance.
pdf.
The
risk
assessment,
and
documents
pertaining
to
the
Agency's
report
on
FQPA
tolerance
reassessment
progress
and
risk
management
decision
for
hexazinone
are
available
on
the
Internet
at
http://
www.
epa.
gov/
pesticides/
reregistration/
status.
htm
and
in
the
public
docket
for
viewing.
The
Agency's
report
on
FQPA
tolerance
reassessment
progress
and
risk
management
decision
for
hexazinone
will
be
announced
in
the
Federal
Register.
Use
Profile
Herbicide:
Hexazinone
is
a
herbicide
registered
for
use
on
alfalfa,
blueberries,
pasture
and
range
grasses,
pineapple,
and
sugarcane.
It
is
also
registered
for
use
on
ornamental
plants,
forest
trees,
and
non
crop
areas.
Hexazinone
works
through
the
inhibition
of
photosynthesis
and
is
used
to
control
a
variety
of
woody
plants
and
weed
species
including
geratum,
alder,
and
alexander
grass.
There
are
no
registered
residential
uses
of
hexazinone
products.
Formulations:
Hexazinone
is
formulated
as
a
dry
flowable
(DF),
emulsifiable
concentrate
(EC),
soluble
concentrate
(SC),
and
as
a
granular
(G).
The
range
of
percentage
of
active
ingredient
in
the
product
formulations
is
10
90%.
Rates,
Methods
and
Timing
of
Application:
The
application
rates
range
from
0.5
5.0
lbs.
active
ingredient
per
acre.
For
agricultural
uses,
the
number
of
applications
per
year
(or
season)
are
typically
limited
to
one.
For
forestry
uses,
the
number
of
applications
are
typically
1
2
applications
over
a
20
to
40
year
period
in
the
East
and
1
2
applications
over
a
60
to
80
year
period
in
the
West.
Hexazinone
formulations
may
be
applied
pre
or
post
emergence
by
layby,
broadcast,
directed
spray,
or
basal
soil
treatments
using
ground
or
aerial
equipment.
Hexazinone
is
mainly
an
early
season
use,
pre
harvest
intervals
(PHIs)
range
from
180
234
days
for
most
uses,
but
PHIs
are
30
and
45
days
for
alfalfa
and
blueberry,
respectively.
Use
Summary:
Approximately
975,000
pounds
of
hexazinone
active
ingredient
are
used
in
the
U.
S.
annually.
Major
Use
Sites
For
Hexazinone:
Alfalfa
represents
approximately
35%
of
the
total
hexazinone
usage
and
forestry
approximately
60%
of
the
usage.
None
of
the
crops
that
comprise
the
remaining
5%
of
use
represents
more
than
1%
of
the
total
usage.
3
Registrant:
Dupont
Human
Health
Risk
Assessment
Acute
Dietary
(Food)
Risk
(For
a
complete
discussion,
see
section
4.2.2
of
the
Human
Health
Risk
Assessment)
Because
no
effects
attributed
to
a
single
exposure
were
identified
for
the
general
population,
the
acute
dietary
exposure
and
risk
assessment
includes
females
13
50
only.
Acute
dietary
risk
from
food
is
calculated
considering
what
is
eaten
in
one
day
(in
this
instance,
the
full
range
of
consumption
values
as
well
as
the
range
of
residue
values
in
food).
A
risk
estimate
that
is
less
than
100%
of
the
acute
Population
Adjusted
Dose
(aPAD)
(the
dose
at
which
an
individual
could
be
exposed
on
any
given
day
and
no
adverse
health
effects
would
be
expected)
does
not
exceed
the
Agency's
level
of
concern.
The
aPAD
is
the
reference
dose
(RfD)
adjusted
for
the
FQPA
Safety
Factor.
Table
1
presents
the
results
of
the
acute
dietary
(food)
exposure
and
risk
analysis
for
females
(13
50
years
of
age).
Table
1.
Acute
Dietary
(Food)
Exposure
and
Risk
Population
Subgroup
Exposure
(mg/
kg/
day)
%
aPAD
Females
(13
50
years)
0.003611
<1.0
°
The
acute
dietary
risk
estimate
does
not
exceed
the
aPAD.
The
acute
dietary
risk
estimate
for
females
13
50
years
old
is
<1.0%
of
the
aPAD.
°
Because
the
toxic
endpoint
for
acute
dietary
exposure
concerns
in
utero
exposure,
the
risk
assessment
is
done
for
females
of
childbearing
age
(13
50)
only.
For
the
female
(13
50
years)
population
subgroup,
the
acute
No
Observed
Adverse
Effect
Level
(NOAEL)
of
400
mg/
kg/
day
was
established,
based
on
decreased
fetal
weight,
malformed
kidneys,
&
skeletal
abnormalities
in
a
rat
developmental
toxicity
study.
The
LOAEL
was
900
mg/
kg/
day.
°
An
uncertainty
factor
(UF)
of
100
was
applied
to
the
doses
selected
for
the
risk
assessment
to
account
for
interspecies
extrapolation
(10x)
and
intraspecies
variability
(10x).
°
For
acute
dietary
exposure,
the
FQPA
safety
factor
was
reduced
to
1X
since
the
toxicology
database
for
hexazinone
contains
acceptable
developmental
and
reproduction
studies
in
the
rat
and
rabbit,
and
there
is
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
in
the
fetuses
or
offspring
in
these
studies.
The
risk
assessment
will
not
underestimate
the
exposure
and
risks
posed
by
hexazinone.
4
°
The
acute
RfD
for
females
13
50:
400
mg/
kg/
day
(NOAEL)
÷
100
(UF)
=
4.0
mg/
kg/
day.
The
acute
PAD
for
females
13
50:
4.0
mg/
kg/
day
÷
1
(FQPA)
=
4.0
mg/
kg/
day.
°
The
acute
dietary
exposure
analysis
is
based
on
the
Dietary
Exposure
Evaluation
Model
(DEEM
™
).
The
DEEM
™
analysis
evaluated
individual
food
consumption
as
reported
by
respondents
in
the
USDA
1989
92
Continuing
Surveys
for
Food
Intake
by
Individuals
(CSFII).
The
data
are
based
on
the
reported
consumption
of
more
than
10,000
individuals
over
three
days.
For
the
acute
exposure
assessment,
individual
one
day
food
consumption
data
are
used
on
an
individual
by
individual
basis.
°
The
acute
dietary
exposure
assessment
for
hexazinone
is
a
tier
I
analysis.
This
is
the
most
conservative
type
of
analysis
done
by
the
Agency
and
it
assumes
that
residues
on
foods
as
consumed
are
equal
to
the
tolerance
levels
and
that
100%
of
each
crop
is
treated.
°
The
dietary
exposure
assessment
included
residue
estimates
of
hexazinone
(parent)
and
metabolites
B,
C,
C
1,
C
2,
and
F
for
ruminant
commodities
and
metabolites
A,
B,
C,
D,
and
E
for
plant
commodities.
The
metabolites
and
parent
hexazinone
are
assumed
to
have
equal
toxicity
based
upon
similarity
in
chemical
structure.
°
Because
existing
data
were
inadequate
to
calculate
residue
estimates
for
pasture
and
rangeland
grass
and
grass
hay,
EPA
constructed
the
maximum
theoretical
dietary
burden
(MTDB)
of
hexazinone
to
livestock
using
protective
assumptions
for
the
contributions
of
other
hexazinonetreated
feed
items.
Thus,
tolerances
for
meats
and
milk
can
be
reassessed.
Additional
field
trial
data
for
grass
forage
and
grass
hay,
as
well
as
rotational
crop
studies
for
corn
and
wheat
are
required.
Because
of
the
relatively
low
volume
of
use
on
pasture
and
rangeland,
data
from
these
confirmatory
studies
are
not
expected
to
significantly
change
current
dietary
risk
estimates.
Chronic
Dietary
(Food)
Risk
(For
a
complete
discussion,
see
section
4.2.3
of
the
Human
Health
Risk
Assessment)
Chronic
dietary
risk
from
food
is
calculated
by
using
the
average
consumption
values
for
food
and
average
residue
values
for
those
foods
over
a
70
year
lifetime.
A
risk
estimate
that
is
less
than
100%
of
the
chronic
PAD
(cPAD)
(the
daily
dose
at
which
an
individual
could
be
exposed
over
the
course
of
a
lifetime
and
no
adverse
health
effects
would
be
expected)
does
not
exceed
the
Agency's
level
of
concern.
Table
2
presents
the
results
of
the
chronic
dietary
(food)
exposure
and
risk
analysis.
Table
2.
Chronic
Dietary
(Food)
Exposure
and
Risk
Population
Subgroup
Exposure
(mg/
kg/
day)
%
cPAD
General
U.
S.
0.002167
4.3
Population
Subgroup
Exposure
(mg/
kg/
day)
%
cPAD
5
All
infants
(<
1
year)
0.003752
7.5
Children
(1
6
years)
0.0077449
15.5
Children
(7
12
years)
0.003964
7.9
Females
(13
50
years)
0.001308
2.6
°
The
chronic
dietary
risk
estimate
for
all
population
subgroups
does
not
exceed
the
cPAD,
all
population
subgroups
are
<16%
of
the
cPAD.
°
For
all
populations,
the
chronic
NOAEL
of
5.00
mg/
kg/
day
was
established,
based
on
severe
body
weight
decrement,
decreased
food
consumption,
and
clinical
chemistry
changes
such
as
anemia,
decreases
in
RBC
counts,
hemoglobin,
and
hematocrit
in
a
one
year
chronic
dog
study
at
the
LOAEL
of
38
mg/
kg/
day.
°
An
uncertainty
factor
(UF)
of
100
was
applied
to
the
doses
selected
for
the
risk
assessment
to
account
for
interspecies
extrapolation
(10x)
and
intraspecies
variability
(10x).
°
For
chronic
dietary
exposure,
the
FQPA
safety
factor
was
reduced
to
1X
for
the
same
reasons
noted
above
for
acute
dietary
exposure.
°
The
chronic
RfD:
5.0
mg/
kg/
day
(NOAEL)
÷
100
(UF)
=
0.05
mg/
kg/
day.
The
chronic
PAD:
0.05
mg/
kg/
day
÷
1
(FQPA)
=
0.05
mg/
kg/
day.
°
The
chronic
dietary
exposure
analysis
is
based
on
the
Dietary
Exposure
Evaluation
Model
(DEEM
™
).
For
chronic
dietary
(food)
assessments,
a
three
day
average
of
consumption
for
each
population
subgroup
is
combined
with
average
residues
in
commodities
to
determine
average
exposures
in
mg/
kg/
day.
°
The
chronic
dietary
(food)
exposure
assessment
for
hexazinone
was
a
tier
I
analysis.
This
is
the
most
conservative
type
of
analysis
the
Agency
performs
and
it
assumes
that
residues
on
foods
as
consumed
are
equal
to
the
tolerance
levels
and
that
100%
of
each
crop
is
treated.
Drinking
Water
Dietary
Risk
(For
a
complete
discussion,
see
section
4.3
of
the
Human
Health
Risk
Assessment)
Drinking
water
exposure
to
pesticides
can
occur
through
surface
and/
or
ground
water
contamination.
EPA
considers
acute
(one
day)
and
chronic
(lifetime)
drinking
water
risks
and
uses
6
either
modeling
or
actual
monitoring
data,
if
available,
to
estimate
those
risks.
Modeling
is
carried
out
in
tiers
of
increasing
refinement,
but
is
designed
to
provide
a
conservative
estimate
of
potential
exposure.
To
determine
the
maximum
allowable
contribution
from
water
allowed
in
the
diet,
EPA
first
looks
at
how
much
of
the
overall
allowable
risk
is
contributed
by
food
and
then
determines
a
Drinking
Water
Level
of
Comparison"
(DWLOC)
to
ascertain
whether
modeled
or
monitored
Estimated
Environmental
Concentrations
(EECs)
exceed
this
level.
The
hexazinone
drinking
water
exposure
assessment
is
based
upon
review
of
environmental
fate
studies
which
suggest
that
the
parent
and
degradates
are
likely
to
be
persistent
and
mobile
in
the
environment.
Leaching
and
runoff
are
expected
to
be
the
primary
dissipation
routes.
Estimated
Environmental
Concentrations
(EECs)
in
surface
waters
were
estimated
using
Tier
I
modeling
(FIRST).
The
EECs
in
groundwater
were
estimated
using
an
available
small
scale
prospective
groundwater
monitoring
study
from
California.
In
addition,
there
are
monitoring
data
available
from
the
state
of
Maine
that
were
used
for
comparison
purposes
only.
°
The
use
of
hexazinone
on
alfalfa
was
modeled
for
the
purpose
of
assessing
surface
drinking
water
exposure
to
the
chemical
and
its
degradates.
Alfalfa
is
the
food/
feed
item
with
the
greatest
percent
of
crop
treated
with
hexazinone.
°
Estimated
Environmental
Concentrations
(EECs)
for
surface
water
were
estimated
using
FIRST
(Tier
I)
modeling.
This
model
is
a
screening
tool
designed
to
provide
high
end
estimates
of
the
concentrations
that
might
be
found
in
a
small
drinking
water
reservoir
due
to
the
use
of
the
pesticides.
°
EECs
for
ground
water
are
based
on
monitoring
data
from
the
small
scale
prospective
groundwater
monitoring
study
in
California.
The
results
of
this
study
were
compared
and
confirmed
with
monitoring
done
in
the
State
of
Maine.
°
The
parent
hexazinone,
G3170,
and
all
degradates
with
conjoined
cyclohexyl
and
triazine
rings
(specifically,
A,
A
1,
B,
C,
D,
1
(JS472),
and
2
(JT677))
are
residues
of
concern
for
risk
assessment
in
water.
The
Agency
assumes
they
have
similar
toxicity
as
the
parent.
Drinking
water
DWLOCs
and
EECs
are
compared
in
Table
3.
7
Table
3.
Acute
and
Chronic
Drinking
Water
DWLOC
and
EEC
Comparisons
Population
Subgroup
Acute
Scenario
Chronic
Scenario
Acute
DWLOC
Ground
Water
EEC
Surface
Water
EEC
Chronic
DWLOC
Ground
Water
EEC
Surface
Water
EEC
U.
S.
General
420
42
47
Females
(13
50
years)
120,000
42
130
420
42
47
All
infants
420
42
47
Children
(1
6
years)
420
42
47
°
For
acute
drinking
water
risk,
potential
(peak)
EECs
of
hexazinone
in
either
ground
water
(42
ppb)
or
surface
water
(130
ppb)
are
below
the
acute
DWLOC
for
females
(13
50
years)
(120,000
ppb).
°
For
chronic
drinking
water
risk,
the
potential
(average)
EECs
of
hexazinone
in
either
ground
water
(42
ppb)
or
surface
water
(47
ppb)
are
below
the
chronic
DWLOC
for
all
population
subgroups
(420
ppb).
Blueberry
Use
In
Maine
A
significant
portion
of
the
wild
blueberry
crop
in
the
state
of
Maine
is
treated
with
hexazinone.
It
may
be
applied
pre
or
post
emergence
at
use
rates
of
0.5
to
2
lb
ai/
acre.
Wild
blueberries
produce
a
berry
crop
every
other
season,
with
hexazinone
being
typically
applied
in
the
non
bearing
year.
A
Special
Local
Need
(SLN)
label
for
Maine,
allows
use
45
days
before
harvest.
Hexazinone
is
the
primary
factor
in
increasing
the
wild
blueberry
crop
three
fold
over
the
past
15
years.
Hexazinone
has
a
half
life
of
90
days,
is
highly
soluble,
and
prone
to
leaching.
Because
most
of
the
wild
blueberry
fields
are
on
highly
leachable
sandy
loam
soils,
there
is
concern
that
ground
and
surface
water
may
be
impacted
by
hexazinone
use.
Water
monitoring
has
been
conducted
since
1985
and
hexazinone
is
detected
in
both
ground
and
surface
water.
Long
term
test
well
data
from
1989
1995
found
concentrations
of
hexazinone
in
the
25
29
ppb.
In
response,
the
Maine
Board
of
Pesticides
Control
implemented
a
Best
Management
System
in
1996
to
reduce
surface
and
groundwater
impact.
The
measures
implemented
by
the
State,
include
classifying
hexazinone
as
a
Restricted
Use
Pesticide.
Users
must
become
certified
applicators
by
attending
training
on
proper
application
techniques.
In
addition,
on
going
field
training
is
provided
for
workers
using
hexazinone.
Application
is
not
allowed
within
50
feet
of
a
water
source
or
well,
airblast
application
is
prohibited,
low
use
rates
are
suggested
except
when
weed
pressure
is
high,
and
alternative
weed
control
measures
are
recommended,
such
as
cutting/
mowing,
burning,
and
hand
pulling
of
weeds.
Recent
monitoring
from
1998
2001
found
8
concentrations
from
0.08
3.8
ppb
in
both
ground
and
surface
water
which
are
significant
reductions
from
the
levels
found
in
the
previous
monitoring.
The
Best
Management
System
implemented
by
the
State
appears
to
be
lowering
the
levels
of
hexazinone
in
ground
and
surface
water.
The
Agency
supports
these
efforts
and
anticipates
their
continued
modification
and
improvement
may
further
reduce
the
levels
of
hexazinone
in
ground
and
surface
water
from
hexazinone
application
to
blueberries.
Nonetheless,
the
levels
of
hexazinone
found
in
ground
and
surface
water
in
Maine
are
well
below
the
acute
DWLOC
(12,000
ppb)
and
the
chronic
DWLOC
(430
ppb)
and
thus,
below
the
Agency's
level
of
concern.
Forestry
Use
and
Tribal
Communities
About
60%
of
hexazinone
usage
is
on
forestry
sites
for
woody
plant
and
weed
control.
Shortly
following
a
logging
operation,
hexazinone
may
be
applied
to
control
brush
in
preparation
for
the
replanting
of
tree
seedlings.
Depending
on
weed
intensity,
hexazinone
may
be
applied
a
second
time
the
next
season
after
the
seedlings
have
been
planted.
The
goal
is
to
suppress
the
competing
vegetation
and
allow
the
seedlings
the
opportunity
to
establish
their
root
system
and
help
them
increase
their
growth
size
above
the
competing
vegetation.
In
Eastern
forests,
because
of
the
species
of
trees
grown,
hexazinone
may
typically
be
applied
1
2
times
during
a
20
to
40
year
period.
In
Western
forests,
hexazinone
may
typically
be
applied
1
2
times
during
a
60
to
80
year
period.
In
some
forested
areas
where
hexazinone
is
applied,
Native
Americans
gather
plant
materials
that
are
used
in
their
diets,
in
the
making
of
traditional
basketry,
for
medicinal
purposes,
and
in
ceremonial
activities.
USEPA,
(Region
IX)
is
working
with
the
California
Department
of
Pesticide
Regulation
(DPR),
the
U.
S.
Forest
Service
(USFS)
and
Native
American
tribes
in
California
to
determine
the
potential
exposure
to
forestry
herbicides,
including
hexazinone,
glyphosate,
and
triclopyr,
that
may
be
occurring
to
Native
Americans
through
their
use
of
forest
plant
materials.
In
response
to
the
health
concerns
raised
by
the
Native
American
communities,
DPR
and
Region
IX
launched
a
risk
assessment
effort
in
1997.
This
effort
includes
five
steps:
DPR
measured
plant
residue
and
surface
water
levels
following
herbicide
application;
DPR
agreed
to
assess
the
total
exposures
and
risks
involved
using,
where
appropriate,
the
monitoring
data
collected;
informing
tribal
physicians
of
state
regulations
requiring
pesticide
illness
reporting;
participation
in
mediated
meetings
with
Native
American
communities
to
determine
the
key
issues
surrounding
herbicide
use;
and
a
video
production
about
inadvertent
exposure
to
herbicides.
In
addition,
the
USFS
is
working
with
local
Indian
tribes,
and
has
established
"no
spray"
zones
where
plant
materials
may
be
gathered
free
of
pesticide
residues.
They
are
also
working
to
reduce
pesticide
usage,
prevent
runoff,
and
minimize
exposure
by
posting
application
sites
and
providing
bulletins
alerting
the
public
where
applications
have,
or
will
occur.
EPA
is
aware
of
this
ongoing
work
and
will
continue
to
coordinate
with
the
registrant
Dupont,
Region
IX,
California
DPR,
U.
S.
Forest
Service,
and
other
entities,
as
appropriate,
to
ensure
that
potential
exposures
and
risks
are
better
characterized.
In
addition,
the
Agency
is
working
to
develop
risk
analysis
software
that
will
assess
risk
from
chemicals
in
food,
air,
water,
and
other
sources
for
9
Native
American
and
Alaska
native
sub
populations
whose
subsistence
ways
of
life
may
result
in
exposures
to
toxic
chemicals
that
are
significantly
different
from
those
of
other
population
sub
groups.
Residential
Risk
Hexazinone
is
not
registered
for
home
use
nor
is
it
used
in
and
around
schools,
or
parks.
Based
on
present
use
patterns
and
labeled
uses,
there
should
be
no
residential
exposure
to
hexazinone.
Thus,
there
is
no
residential
exposure
to
assess
or
aggregate
with
the
dietary
and
drinking
water
exposure.
Aggregate
Risk
(For
a
complete
discussion,
see
section
5.0
of
the
Human
Health
Risk
Assessment)
Aggregate
risk
examines
the
combined
risk
from
exposure
through
food,
drinking
water,
and
residential
uses.
Using
the
DWLOC
approach,
all
risks
from
these
exposures
must
be
less
than
100%
of
the
aPAD
or
cPAD.
For
hexazinone,
the
aggregate
risks
are
limited
to
food
and
water
exposure,
because
there
are
no
residential
uses.
°
Combining
both
the
acute
dietary
(food)
risk
estimates
with
the
surface
and
ground
water
EECs
(drinking
water)
for
hexazinone,
the
acute
aggregate
(food
+
drinking
water)
risk
is
less
than
100%
of
the
aPAD;
and
therefore,
is
not
of
concern
to
the
Agency.
°
Combining
both
the
chronic
dietary
(food)
risk
estimate
with
the
surface
and
ground
water
EECs
(drinking
water)
for
hexazinone,
the
chronic
aggregate
(food
+
drinking
water)
risk
is
less
than
100%
of
the
cPAD,
and
therefore,
is
not
of
concern
to
the
Agency.
Occupational
and
Ecological
Risk
(For
a
complete
discussion,
see
section
4.2
of
the
Human
Health
Risk
Assessment)
Because
hexazinone
is
under
review
for
tolerance
reassessment
only,
no
occupational
or
ecological
risk
assessment
would
normally
be
conducted.
Occupational
and
ecological
risk
management
decisions
were
made
as
part
of
the
1994
Hexazinone
RED.
The
Agency
reevaluated
labeled
uses
and
determined
the
personal
protective
equipment
and
restricted
entry
intervals
included
in
the
RED
are
health
protective.
In
addition,
ecological
tests
indicate
hexazinone
is
non
toxic
to
birds,
bees,
and
fish.
10
Tolerance
Reassessment
Summary
(For
a
complete
discussion,
see
Hexazinone
Residue
Chemistry
Chapter
for
the
Tolerance
Reassessment
Eligibility
Decision
(TRED),
dated
5/
20/
2002.)
The
Agency
has
reassessed
all
25
tolerances
for
hexazinone
and
can
make
an
FQPA
safety
determination.
Anticipated
residues
for
commodities
included
in
the
dietary
risk
assessment
are
equal
to
the
tolerance
levels
and
it
was
assumed
that
100%
of
each
crop
was
treated.
Acute
and
chronic
dietary
risks
from
exposure
to
hexazinone
do
not
exceed
the
Agency's
level
of
concern.
Tolerances
for
residues
of
hexazinone
in/
on
plant,
livestock,
and
processed
commodities
are
currently
expressed
in
terms
of
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone).
Field
trial
data
for
pasture
and
rangeland
grass
hay
will
be
required
as
well
as
rotational
crop
studies
for
corn
and
wheat,
and
are
considered
confirmatory.
Final
tolerances
are
being
proposed
as
part
of
this
Tolerance
Reassessment
Decision
(TRED).
Additional
tolerances
may
be
revised
once
the
field
trial
data
and
rotational
crop
studies
have
been
submitted
to
and
reviewed
by
the
Agency.
Table
4.
Tolerance
Reassessment
Summary
for
Hexazinone.
Commodity
Current
Tolerance
(ppm)
a
Tolerance
Reassessment
(ppm)
Comment/
Correct
Commodity
Definition
Tolerances
presently
listed
under
40
CFR
§180.396(
a):
Alfalfa
green
forage
2.0
2.0
Alfalfa,
forage
Alfalfa
hay
8.0
4.0
Tolerance
should
be
reduced
based
on
re
calculation
of
expected
residues.
Alfalfa,
hay
Blueberries
0.2
0.6
Tolerance
should
be
increased
based
on
the
combined
LOQ
(0.55
ppm)
of
the
enforcement
method.
Blueberry
Cattle,
fat
0.1
Revoke
b
Cattle,
mbyp
0.1
0.1
Cattle,
meat
0.1
0.1
Goat,
fat
0.1
Revoke
b
Goat,
mbyp
0.1
0.1
Goats,
meat
0.1
0.1
Grasses,
pasture
10
TBD
c
Grass,
forage
Commodity
Current
Tolerance
(ppm)
a
Tolerance
Reassessment
(ppm)
Comment/
Correct
Commodity
Definition
11
Grasses,
rangeland
10
TBD
c
Grass,
hay
Hog,
fat
0.1
Revoke
b
Hog,
mbyp
0.1
Revoke
b
Hog,
meat
0.1
Revoke
b
Horses,
fat
0.1
Revoke
b
Horses,
mbyp
0.1
0.1
Horses,
meat
0.1
0.1
Milk
0.5
0.2
Tolerance
should
be
reduced
based
on
re
calculation
of
expected
residues.
Pineapple
0.5
0.6
Tolerance
should
be
increased
based
on
the
combined
LOQ
(0.55
ppm)
of
the
enforcement
method.
Sheep,
fat
0.1
Revoke
b
Sheep,
mbyp
0.1
0.1
Sheep,
meat
0.1
0.1
Tolerances
needed
under
40
CFR
§180.396(
a):
Alfalfa,
seed
2.0
Tolerances
presently
listed
under
40
CFR
§180.396(
c):
Sugarcane
0.2
0.6
Tolerance
should
be
increased
based
on
the
combined
LOQ
(0.55
ppm)
of
the
enforcement
method.
Sugarcane
molasses
5.0
4.0
Tolerance
should
be
reduced
based
on
re
calculation
of
expected
residues.
Sugarcane
molasses
d
5.0
4.0
Tolerance
should
be
reduced
based
on
re
calculation
of
expected
residues.
a
Expressed
in
terms
of
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone).
b
Tolerances
for
fat
are
not
required
(Category
3,
40
CFR
§180.6).
c
TBD:
These
tolerances
require
additional
field
trial
data
and
may
be
revised
once
the
data
have
been
submitted
to
and
reviewed
by
the
Agency.
d
For
reassessment
counting
purposes,
the
Agency
will
count
the
sugarcane
molasses
tolerances
as
two
reassessments
to
reflect
the
tolerances
which
existed
both
in
40
CFR
Part
185
(185.3575)
and
Part
186
(186.3575)
at
the
start
of
FQPA.
12
CODEX
HARMONIZATION
No
maximum
residue
limits
(MRLs)
for
hexazinone
and
its
metabolites
have
been
established
or
proposed
by
Codex
for
any
agricultural
commodity.
Therefore,
no
compatibility
questions
exist
with
respect
to
U.
S.
tolerances.
Summary
of
Pending
Data
The
Agency
is
requesting
a
28
day
inhalation
study
on
a
formulation
with
hexazinone
because
of
the
concern
for
potential
inhalation
exposure.
Additional
field
trial
data
for
grass
hay
and
rotational
crop
studies
for
corn
and
wheat
are
required.
| epa | 2024-06-07T20:31:42.842877 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0003/content.txt"
} |
EPA-HQ-OPP-2002-0188-0005 | Supporting & Related Material | "2002-09-16T04:00:00" | null | July
1,
2002
Mr.
Dirk
V.
Helder
Office
of
Pesticide
Programs
(H7508C)
U.
S.
Environmental
Protection
Agency
1921
Jefferson
Highway
Arlington,
VA
22202
Dear
Mr.
Helder
Subject:
Dupont
Response
to
Draft
Hexazinone
Tolerance
Reassessment
Eligibility
Document
(TRED)
We
appreciate
the
opportunity
to
comment
on
the
draft
TRED
for
hexazinone.
First,
we
compliment
the
Agency
on
the
depth
completeness
of
the
data
base
review.
In
some
areas
covered
in
the
review
we
have
no
significant
comments
and
in
others,
particularly
toxicology,
we
have
extensive
comments
which
are
contained
in
the
attached
documents
identified
for
each
section.
The
most
significant
recommendation,
in
our
view,
contained
in
the
draft
documents
pertains
to
the
revocation
of
tolerances
associated
use
of
hexazinone
on
grass.
We
acknowledge
that
guidelines
and
interpretations
regarding
the
practicality
of
grower
over
cattle
grazing
intervals
have
changed
since
data
supporting
this
use
pattern
were
last
submitted.
However,
as
indicated
review,
this
is
a
rather
minor
use
and
our
information
indicates
that
the
current
label
restrictions
regarding
cutting
and
grazing
being
complied
with.
Therefore,
the
tolerances
supporting
the
use
are
sufficient.
Given
the
foregoing,
we
request
that
the
existing
tolerances
and
use
pattern
be
maintained
while
we
conduct
new
residue
work
to
support
EPA's
interpretation
regarding
a
zero
grazing
interval.
We
understand
that
our
recently
submitted
Rabbit
Developmental
Toxicity
Study
(DuPont
7405,
MRID
45677801)
was
not
in
time
to
be
included
in
the
Draft
TRED.
In
view
of
the
pivotal
importance
of
this
study
to
the
overall
conclusions
of
the
final
(specifically,
the
current
proposal
to
declare
a
significant
gap
in
the
toxicology
data
base,
the
selection
of
appropriate
end
points
regulatory
purposes
and
the
imposition
of
an
additional
10X
safety
factor
due
to
an
incomplete
data
base),
we
respectfully
request
this
study
be
reviewed
as
quickly
as
possible
to
be
included
in
the
final
TRED.
We
also
note
in
the
toxicology
review
that
"Gene
mutation
–
bacterial"
is
listed
as
an
unsatisfied
requirement.
We
have
recently
submitted
(June
28,
2002,
no
MRID
yet
assigned)
a
new
Ames
assay
with
the
75
DF
formulation
which
we
believe
will
satisfy
requirement.
Finally,
we
do
not
believe
a
28
day
inhalation
study
should
be
required
until
the
existing
and
submitted
21
day
inhalation
study
(MRID
00063972)
has
been
reviewed
Again,
we
appreciate
this
opportunity
to
comment
and
look
forward
to
our
continued
collaboration.
Sincerely,
Thomas
F.
Stommel
Global
Product
Reg.
Mgr.
| epa | 2024-06-07T20:31:42.849118 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0005/content.txt"
} |
EPA-HQ-OPP-2002-0188-0006 | Supporting & Related Material | "2002-09-16T04:00:00" | null | HEXAZINONE
TOLERANCE
REASSESSMENT
ELIGIBILITY
DECISION
HED
CHAPTER
–
6/
5/
02
DuPONT
COMMENTS
1.0
Executive
Summary
The
most
significant
recommendation,
in
our
view,
contained
in
the
draft
documents
pertains
to
the
revocation
tolerances
and
associated
use
of
hexazinone
on
grass.
We
acknowledge
that
guidelines
and
interpretations
regarding
the
practicality
of
grower
control
over
cattle
grazing
intervals
have
changed
since
data
supporting
this
use
pattern
were
last
submitted.
However,
as
indicated
in
your
review,
this
is
a
rather
minor
use
and
our
information
indicates
that
the
current
label
restrictions
regarding
cutting
and
grazing
are
being
complied
with.
Therefore,
the
tolerances
supporting
the
use
are
sufficient.
Given
the
above,
we
request
that
the
existing
tolerances
and
use
pattern
be
maintained
while
we
conduct
new
residue
work
to
support
EPA's
interpretation
regarding
a
zero
day
grazing
interval.
We
understand
that
our
recently
submitted
Rabbit
Developmental
Toxicity
Study
(DuPont
7405,
MRID
45677801)
was
not
reviewed
in
time
to
be
included
in
the
Draft
TRED.
In
view
of
the
pivotal
importance
of
study
to
the
overall
conclusions
of
the
final
TRED
(specifically,
the
current
proposal
to
declare
a
significant
gap
in
the
toxicology
data
base,
the
selection
of
appropriate
end
points
for
regulatory
purposes
and
the
imposition
an
additional
10X
safety
factor
due
to
an
incomplete
data
base),
we
respectfully
request
that
this
study
be
reviewed
as
quickly
as
possible
to
be
included
in
the
final
TRED.
We
also
note
in
the
toxicology
review
that
"Gene
mutation
–
bacterial"
is
listed
as
an
unsatisfied
requirement.
have
recently
submitted
(June
28,
2002,
no
MRID
yet
assigned)
a
new
Ames
assay
with
the
75
DF
formulation
which
we
believe
will
satisfy
this
requirement.
Finally,
we
do
not
believe
a
28
day
inhalation
study
should
be
required
until
the
existing
and
submitted
21
day
inhalation
study
(MRID
00063972)
has
been
reviewed.
3.0
Hazard
Characterization
3.1
Hazard
Profile
Table
1:
Acute
Toxicity:
For
Inhalation
LC50>
3.94
mg/
L
(4
hour),
add
(25%
formulation)
Table
2:
Toxicity
Profile:
870.3465,
"A
28
day
inhalation
study
is
required."
As
noted
in
the
HIARC
document,
an
unreviewed
21
day
inhalation
study
is
available
(MRID
00063972)
which
indicates
that
repeated
exposure
to
hexazinone
dust
poses
negligible
inhalation
risks
and
that
no
further
inhalation
testing
should
be
required.
The
Registrant
requests
that
existing
data
be
reviewed
before
additional
testing
is
required.
870.3700b
Prenatal
Developmental
Toxicity
Unacceptable/
Upgradeable.
The
registrant
has
submitted
a
new
rabbit
developmental
study
(DuPONT
7405,
MRID
45677801)
which
addressed
the
deficiencies
and
supports
the
conclusions
of
the
original
study
870.5100
Reverse
mutation
in
Samonella
Strains
Unacceptable:
DuPont
has
conduct
a
Ames
assay
for
the
75DF
formulation
in
both
Salmonella
and
E.
Coli
at
up
to
5000
ug/
plate
(=
3750
ug/
plate
a.
i.)
that
can
be
submitted,
if
needed,
to
satisfy
this
requirement.
The
results
were
negative
for
gene
mutations
in
both
species.
870.5385
In
vivo
Rat
Bone
Marrow
Cytogenetics
Assay
Unacceptable.
Add,
"However
this
Guideline
is
fulfilled
by
an
acceptable
mouse
micronucleus
study."
3.2
FQPA
Considerations
and
3.3
Dose
Response
Assessment:
Acute
Reference
Dose
Females
13
50
The
Agency
assigned
an
additional
10x
database
uncertainty
factor
because
a
rabbit
developmental
study
was
unacceptable
due
to
uncertainties
in
the
LOEL.
A
new
rabbit
developmental
study
(DuPont
7405,
MRID
45677801)
to
the
Agency
which
addresses
the
deficiencies
and
supports
the
previous
study.
Once
the
new
rabbit
study
is
reviewed,
the
registrant
believes
the
extra
10x
uncertainty
factor
should
be
removed.
5.1
Acute
Aggregate
Risk
Assessment
The
headings
for
the
last
three
columns
for
Table
11
(page
42)
should
specify
ug/
l
rather
than
g/
l.
| epa | 2024-06-07T20:31:42.851538 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0006/content.txt"
} |
EPA-HQ-OPP-2002-0188-0007 | Supporting & Related Material | "2002-09-16T04:00:00" | null | HEXAZINONE
TOLERANCE
REASSESSMENT
ELIGIBILITY
DECISION
REPORT
OF
THE
FQPA
SAFETY
FACTOR
COMMITTEE
5/
15/
02
DuPONT
COMMENTS
I.
HAZARD
IDENTIFICATION
3.
Degree
of
Concern
and
Residual
Uncertainties
For
setting
the
acute
reference
dose
(ARfD)
for
females
of
childbearing
age,
the
Agency
assigned
an
additional
10x
database
uncertainty
factor
(UFdb)
because
a
rabbit
developmental
study
was
unacceptable
due
to
uncertainties
in
the
LOEL.
A
UFdb
factor
of
10x
rather
than
3x
was
used
because,
based
on
extrapolation
to
the
rabbit
pilot
NOEL
of
50
mg/
kg
in
the
previous
study,
it
was
concluded
the
difference
between
rabbits
and
rats
may
be
greater
than
3x.
Immediately
after
the
HIARC
report
issued,
the
Registrant
submitted
a
new
rabbit
developmental
study
(DuPont
7405,
MRID
45677801)
to
the
Agency.
The
new
rabbit
developmental
study
was
conducted
using
current
guidelines
and
confirmed
the
results
of
the
previous
rabbit
developmental
study.
The
maternal
and
fetal
rabbit
NOAEL
was
50
mg/
kg/
day.
The
maternal
and
fetal
LOAEL
was
125
mg/
kg/
day
based
on
weight
effects,
which
were
only
slight
in
the
fetus.
A
higher
dose,
175
mg/
kg/
day
produced
severe
maternal
toxicity.
Once
the
new
rabbit
study
is
reviewed,
if
it
is
selected
as
the
basis
of
the
ARfD,
the
registrant
believes
the
extra
10x
UFdb
should
be
removed.
| epa | 2024-06-07T20:31:42.853933 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0007/content.txt"
} |
EPA-HQ-OPP-2002-0188-0008 | Supporting & Related Material | "2002-09-16T04:00:00" | null | HEXAZINONE
TOLERANCE
REASSESSMENT
ELIGIBILITY
DECISION
TOXICOLOGY
CHAPTER
FOR
THE
TRED
5/
30/
02
DuPONT
COMMENTS
2.0
REQUIREMENTS
·
Guideline
Numbers
need
to
be
filled
in
for
Structural
Chromosome
Aberrations
(870.
5375
and
870.5385)
and
Other
Genotoxic
Effects
(870.5550)
·
Although
not
listed
as
a
data
gap,
870.5100
"Gene
mutation
–
bacterial"
is
listed
as
a
requirement
that
is
not
satisfied.
DuPont
has
an
Ames
assay
for
the
75DF
formulation
that
was
conducted
for
another
country.
That
assay
was
conducted
in
both
Salmonella
and
E.
Coli
at
up
to
5000
ug/
plate
(=
3750
ug/
plate
a.
i.)
and
was
negative
for
gene
mutations
in
both.
That
study
can
be
submitted,
if
needed,
to
satisfy
this
requirement.
1.03
DATA
GAPS
1.
It
is
unclear
as
to
why
a
28
day
inhalation
study
is
being
requested.
For
which
risk
assessment
is
it
needed?
There
are
no
residential
uses
of
hexazinone.
Most
of
the
use
patterns
are
outside
the
scope
of
WPS.
The
Agency
comments
on
page
24
of
the
HIARC
document,
that
it
already
has
an
unreviewed
21
day
inhalation
study
(MRID
#
00063972,
HLR
447
76).
In
that
study,
groups
of
ten
male
rats
were
exposed
6
hours/
day,
5
day/
week
for
3
weeks
to
0
(control)
or
2.5
mg/
L
of
90%
wettable
powder
formulation
of
hexazinone
(~
600
mg
a.
i./
kg/
day).
Histopathology
examination
indicated
that
lung
changes
were
similar
between
control
and
hexazinone
exposed
rats.
Intermittent
weight
losses
were
noted
throughout
the
test
period
but
all
rats
showed
a
normal
rate
of
weight
gain
during
the
recovery
period.
The
Registrant
acknowledges
that
this
is
an
old
study
which
was
conducted
prior
to
issuance
of
current
guidelines.
However,
it
indicates
that
repeated
exposure
to
hexazinone
dust
poses
negligible
inhalation
risks
and
that
no
further
inhalation
testing
should
be
required.
2.
A
new
Rabbit
Developmental
Toxicity
Study
has
recently
been
submitted.
(DuPONT
7405,
MRID
45677801)
1.03
HAZARD
ASSESSMENT
4.1
Acute
Toxicity
Page
5
References:
The
references
for
all
the
acute
tox
citations
have
been
omitted
from
the
reference
list.
Should
they
be
included?
Acute
Dermal
Rabbit
Add
date
(1973)
Acute
Inhalation:
Is
not
correct
as
written
since
an
LC50>
3.94
mg/
L
(4
hour)
would
be
a
toxicity
category
IV.
Either
add
a
note
similar
to
that
used
in
the
HIARC
document
(Section
8)
that
this
was
on
a
25%
formulation
AND/
OR
cite
the
1973
study
on
the
technical
material
00104975
LC50>
7.5
mg/
L
(1
hour)
~
LC50
1.9
mg/
L
(4
hours)
that
was
mentioned
in
the
HIARC
report
Section
8.0.
Either
study
(3.94
x
0.25
or
7.5/
4)
would
result
in
a
toxicity
category
III.
4.2
Subchronic
Toxicity
870.3200
Subchronic
Dermal
Page
7
Should
read
"
870.3200
21/
28
Day
Dermal
Toxicity
–
Rabbit"
since
the
guideline
is
for
either
rats
or
rabbits
and
the
study
was
conducted
in
rabbits.
870.3465
Page
8
90
Day
Inhalation
As
described
above,
the
registrant
does
not
agree
that
this
is
a
data
gap
because
the
Agency
has
an
unreviewed
21
day
repeated
dose
inhalation
study
870.3700b
Prenatal
Developmental
Toxicity
Study
–
Rabbit
Page
10
This
should
be
updated
to
reflect
that
a
new
rabbit
developmental
study
was
submitted
(5/
19/
02
MRID
45677801)
4.7
Mutagenicity
For
clarification,
we
recommend
inserting
the
following
wording
into
the
last
sentence
of
the
mutagenicity
overview
(additions
are
in
bold).
"Because
unambiguous
positive
results
were
achieved,
it
was
concluded
that
the
study
provided
adequate
evidence
that
INA
3674
112
(hexazinone
technical)
is
clastogenic
in
vitro
in
an
acceptable
study.
However,
negative
results
were
obtained
in
two
studies
which
assessed
chromosome
damage
in
vivo."
4.7.3
Page
20
870.5375
Mid
paragraph
"In
the
presence
of
S
9
mix,
no
statistically
significant
increases
in
chromosome
aberrations
were
seen
in
Trial
1;
however,
very
low
positive
control
values
indicated
a
problem
with
the
S9
mix."
Delete
the
latter
part
of
the
sentence;
it
is
incorrect.
Positive
control
values
in
both
trials
produced
strong
positive
results
(Trial
1
28
32%
abnormal
cells,
Trial
2
36
40%
abnormal
cells).
4.7.4
Page
21
870.5385
After,
"Unacceptable….
The
study
does
not
satisfy
the
requirement
for
FIFRA
Test
Guidelines."
Add,
"However
this
Guideline
is
fulfilled
by
an
acceptable
mouse
micronucleus
study."
4.7.5
Page
22
870.5395
Change
the
last
sentence
from
"It
satisfy
the
requirements…."
to
"It
satisfies
the
requirements…."
6.0
FQPA
CONSDERATIONS
6.1
Page
25
The
Agency
assigned
an
additional
10x
database
uncertainty
factor
(UFdb)
because
a
rabbit
developmental
study
was
unacceptable
due
to
uncertainties
in
the
LOEL.
Immediately
after
the
HIARC
report
issued,
the
Registrant
submitted
a
new
rabbit
developmental
study
(DuPont
7405,
MRID
45677801)
to
the
Agency.
The
new
rabbit
developmental
study
was
conducted
using
current
guidelines
and
confirmed
the
results
of
the
previous
rabbit
developmental
study.
The
maternal
and
fetal
rabbit
NOAEL
was
50
mg/
kg/
day.
The
maternal
and
fetal
LOAEL
was
125
mg/
kg/
day.
Once
the
new
rabbit
study
is
reviewed,
if
it
is
selected
as
the
basis
of
the
ARfD,
the
registrant
believes
the
extra
10x
UFdb
should
be
removed.
8.0
REFERENCES
Acute
Toxicity
references
have
been
omitted.
9.0
APPENDICES
Insert
page
break
before
appendices
9.1.1
Acute
Toxicity
Table
Header
should
read:
"Acute
Toxicity
Data
on
HEXAZINONE"
NOT
"Acute
Toxicity
Data
on
FENBUTATIN
OXIDE"
9.1.2
Subchronic,
Chronic,
and
Other
Toxicity
Tables
Registrant
comments
have
been
made
above
regarding
removal
of
the
28
day
inhalation
study
requirement,
the
submission/
MRID
of
a
new
prenatal
developmental
study,
and
the
availability
of
an
unsubmitted
gene
mutation
assay
(with
a
75DF
formulation)
in
Salmonella
and
E.
Coli.
9.2
Summary
of
Toxicological
Endpoints
Registrant
restates
that
additional
10x
UFdb
should
be
removed
after
new
rabbit
developmental
toxicity
study
is
reviewed
and
questions
the
need
for
establishment
of
long
term
occupational
endpoints.
| epa | 2024-06-07T20:31:42.855699 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0008/content.txt"
} |
EPA-HQ-OPP-2002-0188-0009 | Supporting & Related Material | "2002-09-16T04:00:00" | null | HEXAZINONE
TOLERANCE
REASSESSMENT
ELIGIBILITY
DECISION
REPORT
OF
THE
HAZARD
IDENTIFICATION
ASSESSMENT
(HIARC)
REVIEW
OF
4/
25/
02
DuPONT
COMMENTS
2
HAZARD
IDENTIFICATION
1.1
Acute
Dietary
Reference
Dose
Females
13
50
pp.
3
5
For
setting
the
acute
reference
dose
(ARfD)
for
females
of
childbearing
age,
the
Agency
has
selected
a
rat
developmental
study
with
NOAELs
of
100
and
400
mg/
kg
for
maternal
and
fetal
effects,
respectively.
The
Agency
assigned
an
additional
10x
database
uncertainty
factor
(UFdb)
because
a
rabbit
developmental
study
was
unacceptable
due
to
uncertainties
in
the
LOEL.
A
UFdb
factor
of
10x
rather
than
3x
was
used
because,
based
on
extrapolation
to
the
rabbit
pilot
NOEL
of
50
mg/
kg
in
the
previous
study,
it
was
concluded
the
difference
between
rabbits
and
rats
may
be
greater
than
3x.
The
resulting
ARfD
was
0.4
mg/
kg
(400
mg/
kg
/
1000).
Immediately
after
the
HIARC
report
issued,
the
Registrant
submitted
a
new
rabbit
developmental
study
(DuPont
7405,
MRID
45677801)
to
the
Agency.
The
new
rabbit
developmental
study
was
conducted
using
current
guidelines
and
confirmed
the
results
of
the
previous
rabbit
developmental
study.
The
maternal
and
fetal
rabbit
NOEL
was
50
mg/
kg/
day.
The
maternal
and
fetal
LOEL
was
125
mg/
kg/
day
based
on
weight
effects,
which
were
only
slight
in
the
fetus.
A
higher
dose,
175
mg/
kg/
day
produced
severe
maternal
toxicity.
Once
the
new
rabbit
study
is
reviewed,
if
it
is
selected
as
the
basis
of
the
ARfD,
the
registrant
believes
the
extra
10x
UFdb
should
be
removed.
If
selected,
this
would
result
in
an
ARfD
of
0.5
mg/
kg
(50
mg/
kg
/
100).
This
is
essential
the
same
(slight
improvement)
as
the
current
ARfD,
and
thus
there
will
be
essentially
no
change
in
the
acute
dietary
risk
assessment.
2.3
Chronic
Reference
Dose
Last
line
page
6
–
typographical
error.
"The
LOAEL
is…
based
on…[
findings
listed]
and
clinical
observations
of
thinnest
in
one
male."
Should
read
"thin
appearance
in
one
male."
1.4
Occupational/
Residential
Exposure
It
is
not
clear
to
the
Registrant
why
the
occupational
and
residential
exposure
Sections
2.4.1
through
2.6
were
included
in
a
food
Tolerance
Reassessment.
There
are
no
residential
uses
of
hexazinone,
that
could
contribute
to
the
aggregate
exposure.
It
is
the
Registrant's
understanding
that
occupational
exposure
assessment
is
beyond
the
scope
of
Tolerance
Reassessment.
Occupational
exposure
was
addressed
under
the
1994
Reregistration
Eligibility
Document.
It
was
noted
that
a
number
of
the
major
uses
of
hexazinone
were
outside
the
scope
of
the
Worker
Protection
Standard
(WPS).
While
agricultural
uses
and
use
on
sod
farms
was
within
WPS;
use
on
pastures,
rangeland,
plants
grown
for
other
than
commercial
purposes,
ornamental
plants
in
parks
and
golf
course,
and
no
agricultural
uses
such
as
vegetation
along
rights
of
way
were
outside
of
the
scope
of
WPS.
No
worker
exposure
assessment
was
conducted.
Therefore
the
Registrant
considers
the
selection
of
Occupational/
Residential
endpoints
(e.
g.,
dermal
and
inhalation
exposure
scenarios)
to
not
be
relevant
to
Tolerance
Reassessment.
Nonetheless,
we
offer
the
following
comments
to
the
endpoint
selection,
should
these
endpoints
be
considered
relevant
in
the
future.
2.4.2
Dermal
Absorption
The
review
states
that
"No
dermal
absorption
study
is
available."
It
would
be
clearer
to
say
that
"No
dermal
penetration
study
is
available.
For
an
estimate
of
dermal
penetration,
the
NOAEL
from
the
21
day
rabbit
dermal
toxicity
study…."
Also,
for
clarification,
add
the
MRID
of
the
rabbit
21
day
study
(MRID
41309005).
The
Agency
extrapolated
a
dermal
absorption
factor
by
comparing
the
NOAEL
in
a
21
day
dermal
study
in
rabbits
to
the
LOAEL
from
a
rabbit
developmental
range
finding
study.
A
25%
dermal
absorption
factor
was
derived.
Rabbit
Pilot
Developmental
LOAEL
(oral)
=
250
mg/
kg
=
25%
Rabbit
21
Day
Dermal
NOAEL
1000
mg/
kg
However,
the
new
rabbit
developmental
study
(DuPont
7405,
MRID
45677801)
indicates
there
is
a
greater
difference
between
oral
and
dermal
toxicity
than
indicated
by
the
above
calculation.
Further,
since
no
LOAEL
was
actually
established
on
the
Rabbit
21
Day
Dermal
study,
use
of
a
dermal
NOAEL
in
comparison
to
an
oral
LOAEL,
overestimates
the
potential
dermal
penetration.
Based
on
the
new
rabbit
developmental
study,
dermal
absorption
is
no
greater
than
12.5%
Rabbit
Developmental
LOAEL
(oral)
=
125
mg/
kg
=<
12.5%
Rabbit
21
Day
Dermal
NOAEL
>
1000
mg/
kg
2.4.3
Short
Term
(1
Day
–
1
Month)
Dermal
Exposure
and
2.4.4
Intermediate
Term
(1
6
Months)
and
Long
Term
(>
6
Months)
Dermal
Exposures
Under
2.4.3,
the
Agency
states
the
Dose
and
Endpoint
for
Risk
Assessment
for
short
term
dermal
Exposure
is
Not
Applicable
and
that
No
Hazard
and
No
Quantification
are
required
(based
on
no
effects
in
the
21
day
dermal
study
in
rabbits).
However,
in
the
next
section
(2.4.4)
the
Agency
proceeds
to
select
longer
term
dermal
endpoints
based
on
the
chronic
dog
study
NOEL
(5
mg/
kg/
day)
and
a
25%
dermal
absorption
factor
(i.
e.
equivalent
to
20
mg/
kg/
day).
For
intermediate
term
scenarios,
we
believe
selection
of
a
subchronic
endpoint
would
be
more
appropriate
than
selection
of
the
chronic
dog
study
with
a
25%
absorption
factor.
It
is
also
consistent
wit
the
Agency
guidance
document,
Toxicology
Endpoint
Selection
Process
(February,
1997).
Based
on
the
labeled
uses
for
hexazinone,
we
do
not
believe
a
long
term
dermal
exposure
scenario
is
relevant.
It
is
difficult
to
identify
a
scenario
where
there
would
be
daily,
lifetime
uninterupted
dermal
exposure
to
hexazinone.
·
The
registrant
believes
that
the
route
specific
rabbit
dermal
study
is
the
most
appropriate
study
to
estimate
subchronic
human
dermal
exposure.
The
Agency
has
concluded
that
the
repeated
dose
rabbit
study
(MRID
41309005)
meets
guidelines
and
is
acceptable.
It
measured
the
proper
endpoints
to
identify
hexazinone
toxicity
(including
body
weights,
clinical
chemistry,
liver
histology).
Considering
lifespan
differences,
it
is
of
appropriate
duration
for
short
term
and
intermediate
endpoint
selection.
·
However,
if
the
Agency
deems
that
the
duration
of
the
subchronic
rabbit
dermal
study
is
insufficient,
acceptable
subchronic
oral
studies
of
longer
duration
(90
days)
are
available.
The
NOAELs
from
the
rat
and
dog
90
day
studies
were
84
and
29
mg/
kg,
respectively.
Again
the
dog
is
the
most
sensitive
species,
but
the
subchronic
NOAEL
is
more
appropriate.
·
As
noted
in
the
discussion
above,
the
25%
absorption
factor
derived
by
comparing
a
LOAEL
on
a
rabbit
pilot
developmental
study
to
the
NOAEL
on
the
rabbit
subchronic
dermal
study
overestimated
the
Dermal
Absorption
Factor
which,
in
reality,
is
likely
to
be
less
than
12.5%.
Using
the
dog
subchronic
NOAEL
(29
mg/
kg/
day)
and
applying
a
more
appropriate
dermal
absorption
factor
<12.5%
would
result
in
an
estimated
dermal
endpoint
of
>
232
mg/
kg/
day.
This
is
much
more
comparable
to
the
actual
dermal
NOAEL
determined
from
the
21
day
rabbit
study.
Also
typographical
error
in
2.4.4
"thinnest
in
one
males"
should
read
"thin
appearance
in
one
male"
2.4.6
Intermediate
(1
6
Months)
and
Long
Term
(>
6
Months)
Inhalation
Exposure
Typographical
error
"thinnest
in
one
males"
should
read
"thin
appearance
in
one
male"
4
MUTAGENICITY
For
clarification,
we
recommend
inserting
the
following
wording
into
the
last
sentence
of
the
mutagenicity
overview
(additions
are
in
bold).
"Because
unambiguous
positive
results
were
achieved,
it
was
concluded
that
the
study
provided
adequate
evidence
that
INA
3674
112
(hexazinone
technical)
is
clastogenic
in
vitro
in
an
acceptable
study.
However,
negative
results
were
obtained
in
two
studies
which
assessed
chromosome
damage
in
vivo."
General
Comment:
for
consistency
with
the
rest
of
the
document,
INA
3674
112
should
be
changed
to
hexazinone
or
hexazinone
technical.
Guideline
870.5300:
Gene
Mutation
Assay
in
Mammalian
Cells
Conclusion
should
be
bolded
as
with
others
studies.
"There
was,
however,
no
indication
that
INA
3674
112
induced
mutagenic
effect
in
either
the
presence
or
the
absence
of
S9
activation."
Guideline
870.5395:
Mouse
Bone
Marrow
Micronucleus
Assay
Change
the
last
sentence
from
"It
satisfy
the
requirements…."
to
"It
satisfies
the
requirements…."
Guideline
870.5375:
Structural
Chromosome
Aberration
Assay;
In
vitro
Cytogenetic
Assay
Mid
paragraph
"In
the
presence
of
S
9
mix,
no
statistically
significant
increases
in
chromosome
aberrations
were
seen
in
Trial
1;
however,
very
low
positive
control
values
indicated
a
problem
with
the
S9
mix."
Delete
the
latter
part
of
the
sentence;
it
is
incorrect.
Positive
control
values
in
both
trials
produced
strong
positive
results
(Trial
1
28
32%
abnormal
cells,
Trial
2
36
40%
abnormal
cells).
Guideline
870.5385:
Structural
Chromosome
Aberration
Assay;
In
vivo
Cytogenetic
Assay
Fourth
sentence
of
second
paragraph,
"Few
or
no
analyzable
cell
were
available…"
should
be
"Few
or
no
analyzable
cells
were
available…"
After,
"Unacceptable….
The
study
does
not
satisfy
the
requirement
for
FIFRA
Test
Guidelines."
add,
"However,
this
Guideline
is
fulfilled
by
an
acceptable
mouse
micronucleus
study."
5
FQPA
CONSIDERATIONS
4.3
Developmental
Toxicity
5.3.2.
Developmental
Toxicity
in
the
Rabbit
Last
paragraph
should
be
upgraded
to
indicate
a
Rabbit
Developmental
Toxicity
(45677801)
has
just
been
submitted
but
not
yet
been
reviewed.
5.7
Determination
of
the
Need
for
Developmental
Neurotoxicity
Study
4.6.1
Evidence
that
suggest
requiring
a
Developmental
Neurotoxicity
Study
Atrazine
should
not
be
considered
as
evidence
suggesting
requirement
of
a
developmental
neurotoxicity.
Although
atrazine
and
hexazinone
contain
a
triazine
ring,
there
are
significant
structural
differences
that
contribute
substantial
differences
in
the
biological
response
to
these
molecules
by
laboratory
animals.
EPA
reached
a
similar
conclusion
in
the
Toxicology
Disciplinary
Chapter
for
the
Tolerance
Reassessment
and
Evaluation
Decision
Document,
Section
1.0
–
Hazard
Characterization
(May
16,
2002).
The
critical
structural
differences
include
substitutions
of
a
cyclohexyl
and
a
methyl
group
on
the
ring
nitrogens
and
the
presence
of
two
ring
oxo
groups
in
hexazinone.
As
a
result,
hexazinone
is
less
aromatic
in
character
than
the
chloro
s
triazines.
Collectively,
these
structural
differences
are
considered
to
contribute
differences
in
toxicological
properties.
Hexazinone
has
been
classified
as
a
triazine
dione
by
EPA,
which
further
indicates
this
Agency
acknowledges
its
differences
from
the
chloro
striazine
herbicide
class.
Hexazinone
has
been
extensively
tested
for
safety
to
mammals.
A
key
difference
between
hexazinone
and
atrazine
and
other
members
of
the
chloro
s
triazine
class
is
that
chronic
exposures
to
the
latter
produce
a
characteristic
mammary
tumor
response
in
Sprague
Dawley
rats.
The
mode
of
action
for
this
chloro
s
triazine
induced
tumor
response
has
been
associated
with
altered
endocrine
activity
unique
to
this
rat
strain.
In
contrast
hexazinone
does
not
induce
rat
mammary
tumors,
which
indicates
the
absence
of
the
endocrine
modulation
responsible
for
this
effect.
Additional
evidence
supporting
the
absence
of
endocrine
effects
with
hexazinone
includes
the
absence
of
endocrine
organ
effects
and
effects
on
reproduction
and
development.
The
differences
in
chemical
structures
are
considered
to
be
critical
to
the
observed
differences
in
toxicological
response
between
hexazinone
and
the
chloro
s
triazines.
7.
Data
Gaps
"HIARC
has
requested
a
28
day
inhalation
study
because
of
the
concern
for
inhalation
exposure
based
on
the
use
pattern"
·
It
is
unclear
as
to
which
use
pattern
is
being
considered.
There
are
no
residential
uses
of
hexazinone.
Most
of
the
use
patterns
are
outside
the
scope
of
WPS.
Since
no
use
patterns
of
concern
are
identified,
it
is
impossible
to
determine
duration
of
exposure.
·
On
the
same
page
that
it
requests
a
28
day
inhalation
study,
the
Agency
notes
that
it
already
has
an
unreviewed
21
day
inhalation
study
(MRID
#
00063972,
HLR
447
76).
In
that
study,
groups
of
ten
male
rats
were
exposed
6
hours/
day,
5
day/
week
for
3
weeks
to
0
(control)
or
2.5
mg/
L
of
90%
wettable
powder
formulation
of
hexazinone.
Using
the
guidance
in
(Whalan
EPA,
1997)
this
represents
an
exposure
of
greater
than
600
mg/
kg/
day
(2.25
mg
hexazinone
a.
i./
L
x
11.38
L/
hr
respiration
x
6
hr/
day
exposure/
0.25
kg
body
weight
).
Histopathology
examination
indicated
that
lung
changes
were
similar
between
control
and
hexazinone
exposed
rats.
Intermittent
weight
losses
were
noted
throughout
the
test
period
but
all
rats
showed
a
normal
rate
of
weight
gain
during
the
recovery
period
.
The
Registrant
acknowledges
that
this
is
an
old
study
which
was
conducted
prior
to
issuance
of
current
guidelines.
However,
it
clearly
indicates
that
repeated
exposure
to
hexazinone
dust
poses
negligible
inhalation
risk.
It
also
suggests
that
no
further
inhalation
testing
is
required
since
no
lung
toxicity
was
identified
and
since
the
exposure
producing
minimal
to
moderate
toxicity
was
two
orders
of
magnitude
higher
than
the
chronic
NOAEL
that
has
just
been
selected
by
the
Agency
to
set
an
inhalation
endpoint.
Therefore
the
oral
endpoint
selected
is
overly
protective.
In
the
interest
of
conservation
of
animals
we
strongly
urge
that
available
information
be
considered
before
the
Agency
request
another
study
and
the
repeated
dose
inhalation
be
removed
as
a
data
gap.
For
the
rabbit
developmental
toxicity
data
gap
we
recommend
changing
the
statement
"is
expected
to
be
submitted"
to
"was
not
submitted
in
enough
time
for
review
prior
to
issuance
of
this
document"
| epa | 2024-06-07T20:31:42.858512 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0009/content.txt"
} |
EPA-HQ-OPP-2002-0188-0010 | Supporting & Related Material | "2002-09-16T04:00:00" | null | HEXAZINONE
TOLERANCE
REASSESSMENT
ELIGIBILITY
DECISION
ACUTE
AND
CHRONIC
DIETARY
RISK
ASSESSEMENT
DATED
05/
14/
2002
DuPONT
COMMENTS:
General
comments
Dietary
Risk
Assessment
1.
An
acute
endpoint
is
only
given
for
females
13
50.
We
assume
this
group
is
considered
by
EPA
to
be
the
most
sensitive
sub
population.
2.
In
several
places
we
note
the
risk
assessment
is
'based
on
the
reassessed
tolerances
for
blueberry,
pineapple,
and
sugarcane.
'
For
blueberries
and
pineapple
0.3
ppm
is
utilized,
presumably
one
half
of
the
new
proposed
tolerance
of
0.6ppm.
However,
for
sugarcane
0.6
ppm
(tolerance)
is
utilized.
This
appears
to
be
an
inconsistency.
Stated
differently,
it
is
not
clear
to
us
why
0.3ppm
was
selected
for
blueberry
and
pineapple
while
0.6
was
selected
for
sugarcane.
3.
Clarity
is
needed
around
the
definition
of
LOQ.
There
are
both
enforcement
methods
(sum
of
LOQs
is
0.55
ppm)
and
data
collection
methods
(sum
of
LOQs
is
0.3
ppm).
We
recommend
that
the
enforcement
LOQs
be
used
consistently
throughout
the
document.
4.
We
note
that
a
more
up
to
date
consumption
database
exists,
CSFII
94
96/
98.
Why
was
the
older
database,
CSFII
89
92,
used?
Editorial
Comment
Typo:
p2
Third
full
paragraph,
2nd
line
from
bottom:
residue
| epa | 2024-06-07T20:31:42.861811 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0010/content.txt"
} |
EPA-HQ-OPP-2002-0188-0011 | Supporting & Related Material | "2002-09-16T04:00:00" | null | U.
S.
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
DC
20460
.
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
PC
Code:
107201
DP
Barcode:
D215026;
D268715
MEMORANDUM
SUBJECT:
Tier
I
Estimated
Environmental
Concentrations
of
Hexazinone,
for
use
in
Human
Health
Risk
Assessment
FROM:
Larry
Liu,
Ph.
D.,
Environmental
Scientist
ERB
V,
Environmental
Fate
and
Effects
Division
(7507C)
THROUGH:
Mah
T.
Shamim,
Ph.
D.,
Chief
Environmental
Risk
Branch
V
Environmental
Fate
and
Effects
Division
(7507C)
TO:
Margaret
Rice,
Chief
Dirk
Helder,
Chemical
Reviewer
Manager
Reregistration
Branch
II
Special
Review
and
Reregistration
Division
(7508C)
and
Sherrie
Kinard,
Residue
Chemist
Carol
Christenson,
Risk
Assessor
RRB
II,
Health
Effects
Division
(7509C)
This
memorandum
presents
the
Tier
I
Estimated
Environmental
Concentrations
(EECs)
for
the
herbicide
hexazinone
for
use
in
the
human
health
risk
assessment.
EEC's
on
surface
waters
were
estimated
using
the
Tier
I
model
FIRST.
The
EEC's
on
groundwaters
were
estimated
using
an
available
small
scale
prospective
groundwater
monitoring
study.
This
memorandum
also
provides
information
about
the
groundwater
prospective
small
scale
study
conducted
by
the
registrant,
and
how
it
was
used
to
estimate
the
total
hexazinone
residues
in
ground
waters.
In
addition,
monitoring
data
available
from
the
state
of
Maine
was
presented.
The
surface
water
concentrations,
for
hexazinone
residues
were
as
follows:
acute
(peak)
value,
130
ppb,
and
the
chronic
annual
average
value,
47
ppb,
based
on
the
application
of
hexazinone
on
alfalfa,
which
is
the
major
food
crop
for
the
chemical.
The
groundwater
screening
concentration
for
hexazinone
residues
is
41.8
ppb.
These
values
represent
upper
bound
estimates
of
the
concentrations
that
might
be
found
in
surface
water
and
groundwater
due
to
the
use
of
hexazinone
on
representative
crops.
It
is
noted
that
the
groundwater
screening
concentration
for
hexazinone
residues,
based
on
the
groundwater
prospective
monitoring
study
is
of
the
same
order
of
magnitude
than
the
groundwater
concentration
estimated
from
the
Tier
I
model
SCIGROW
(i.
e.,
20.2
ppb).
2
Should
the
results
of
this
assessment
indicate
a
need
for
further
refinement,
please,
contact
us
as
soon
as
possible
so
that
we
may
schedule
a
Tier
II
assessment.
Hexazinone
Environmental
Fate
Properties
Based
on
the
available
information,
hexazinone
appears
to
be
persistent
and
mobile
in
soil
and
aquatic
environments.
The
mobility
of
hexazinone
was
demonstrated
in
batch
equilibrium
data.
The
field
and
forestry
dissipation
data
also
confirm
that
hexazinone
is
persistent
and
mobile.
Furthermore,
the
batch
equilibrium
data
also
suggest
that
its
degradates
are
very
mobile.
Based
on
the
environmental
fate
properties
of
hexazinone
and
its
degradates,
it
can
be
concluded
they
may
be
of
concern
for
surface
water
and
groundwater
contamination..
The
following
table
summarizes
the
environmental
fate
properties
of
hexazinone,
and
the
adsorption
data
for
its
degradates:
Water
solubility
=
33,000
ppm
(25
C)
Vapor
pressure
=
2x10
7
mm
Hg
Kow
=
15
Henry's
Law
Constant
=
2x10–
12
atm
m3/
mol
Summary
of
Environmental
Fate
Properties
of
Hexazinone:
Study
Type/
Hexazinone
Half
Life
Source
(MRID)
Hydrolysis
pH
5
stable
41587301
(acceptable)
pH
7
stable
41587301
(acceptable)
pH
9
stable
41587301
(acceptable)
Aqueous
Photolysis
(pH
7)
stable
41300801
(acceptable)
Soil
Photolysis
82
days
41300802
(acceptable)
Aerobic
Soil
216
days
41807401;
42635001
(acceptable)
Anaerobic
Aquatic
230
days
41807402
(acceptable)
Aerobic
Aquatic
60
days
41811801
(acceptable)
3
Summary
of
Environmental
Fate
of
Hexazinone
(continued):
Adsorption
(Mobility)
Studies
Kd
KOC
Source
(MRID)
Hexazinone
0.45
37
41528101
(acceptable)
Hexazinone
0.18
50
43621501
(supplemental)
Degradate
A
1
0.03
27
43621501
(supplemental)
Degradate
2
0.15
45
43621501
(supplemental)
Degradate
H
0.31
51
43621501
(supplemental)
Degradate
D
0.34
59
43621501
(supplemental)
Degradate
B
0.44
90
43621501
(supplemental)
Degradate
1
0.20
122
43621501
(supplemental)
Degradate
A
0.69
176
43621501
(supplemental)
Field
Studies/
Hexazinone
Half
Life
Source
(MRID)
Field
Dissipation
Delaware
123
day
(parent
was
detected
<
30
cm)
42377901
(acceptable)
Mississippi
154
day
(parent
was
detected
>
60
75
cm)
42377901
(acceptable)
Forest
Dissipation
Litter
covered
soil
265
days
42379201
(supplemental)
Degradate
Profile
The
following
table
summarizes
the
degradates
detected
in
the
laboratory
fate
studies
and/
or
monitored
in
the
field
dissipation
and
the
groundwater
study
(i.
e.,
Degradates
A,
A
1,
C,
D,
1,
2,
and
G3170).
It
should
be
noted
that:
C
although
Degradate
C
was
not
found
in
any
of
the
laboratory
fate
studies,
the
field
dissipation
and
the
small
scale
prospective
groundwater
monitoring
study
monitored
this
degradate;
the
registrant
indicated
that
the
degradate
was
observed
in
aerobic
soil
metabolism
studies
with
acidic
soils;
C
Degradates
D
and
2
were
the
major
degradates
found
in
the
anaerobic
aquatic
metabolism
study;
however,
the
field
dissipation
and
the
small
scale
prospective
groundwater
monitoring
studies
did
not
monitor
these
two
degradates.
Therefore,
the
fate
of
Degradates
D
and
2
could
not
be
assessed
under
natural
environment;
the
registrant
believed
that
both
field
studies
were
mostly
aerobic
and
the
degradates
were
unlikely
to
be
observed;
and,
4
C
the
field
dissipation
studies
did
not
monitor
the
fate
of
Degradate
G
3170
which
was
the
degradate
detected
at
the
highest
concentrations
in
the
small
scale
prospective
groundwater
monitoring
study
(MRID
45132801);
this
degradate
was
not
observed;
however,
in
the
aerobic
soil
metabolism
study.
C
Summary
of
Degradates
Found
in
the
Environmental
Fate
Studies
Maximum
Degradate
Concentration
(%
of
applied)
and
Time
(days)
to
Maximum
Concentration
in
Study:
Degradates
Analyzed
in
Study:
Degradate
Soil
Photo.
Aerobic
Soil
Anaerobic.
Aquatic
Aerobic
Aquatic
Field
Diss.
Ground
Water
A
(T3937)
5.5%
(365d)
yes
yes
A
1
(G3453)
18.7%
(365d)
<10.0%
(56d)
yes
yes
B
(A3928)
10.1%
(30d)
2.3%
(365d)
<10.0%
(56d)
yes
yes
C
(T3935)
yes
yes
D
(B2838)
4.8%
(365d)
24.0%
(365d)
<10.0%
(56d)
1
((
JS472)
10.9%
(365d)
<10.0%
(56d)
yes
yes
2
(JT677)
25.0%
(365d)
G3170
yes
Background
Information
on
FIRST
FIRST
is
a
new
screening
model
designed
to
estimate
the
pesticide
concentrations
found
in
water
for
use
in
drinking
water
assessments.
It
provides
high
end
values
on
the
concentrations
that
might
be
found
in
a
small
drinking
water
reservoir
due
to
the
use
of
pesticide.
Like
GENEEC,
the
model
previously
used
for
Tier
I
screening
level,
FIRST
is
a
single
event
model
(one
run
off
event),
but
can
account
for
spray
drift
from
multiple
applications.
FIRST
uses
a
Drinking
Water
Reservoir
instead
of
a
pond
as
the
standard
scenario.
The
FIRST
scenario
includes
a
427
acres
field
immediately
adjacent
to
a
13
acres
reservoir,
9
feet
deep,
with
continuous
flow
(two
turnovers
per
year).
The
pond
receives
a
5
spray
drift
event
from
each
application
plus
one
runoff
event.
The
runoff
event
moves
a
maximum
of
8%
of
the
applied
pesticide
into
the
pond.
This
amount
can
be
reduced
due
to
degradation
on
field
and
the
effect
of
binding
to
soil.
Spray
drift
is
equal
to
6.4%
of
the
applied
concentration
from
the
ground
spray
application
and
16%
for
aerial
applications.
FIRST
also
makes
adjustments
for
the
percent
crop
area.
While
FIRST
assumes
that
the
entire
watershed
would
not
be
treated,
the
use
of
a
PCA
is
still
a
screen
because
it
represents
the
highest
percentage
of
crop
cover
of
any
large
watershed
in
the
US,
and
it
assumes
that
the
entire
crop
is
being
treated.
Various
other
conservative
assumptions
of
FIRST
include
the
use
of
a
small
drinking
water
reservoir
surrounded
by
a
runoff
prone
watershed,
the
use
of
the
maximum
use
rate,
no
buffer
zone,
and
a
single
large
rainfall.
Background
Information
on
SCI
GROW
SCI
GROW
provides
a
groundwater
screening
exposure
value
to
be
used
in
determining
the
potential
risk
to
human
health
from
drinking
water
contaminated
with
the
pesticide.
Since
the
SCI
GROW
concentrations
are
likely
to
be
approached
in
only
a
very
small
percentage
of
drinking
water
sources,
i.
e.,
highly
vulnerable
aquifers,
it
is
not
appropriate
to
use
SCI
GROW
for
national
or
regional
exposure
estimates.
SCI
GROW
estimates
likely
groundwater
concentrations
if
the
pesticide
is
used
at
the
maximum
allowable
rate
in
areas
where
groundwater
is
exceptionally
vulnerable
to
contamination.
In
most
cases,
a
large
majority
of
the
use
area
will
have
groundwater
that
is
less
vulnerable
to
contamination
than
the
areas
used
to
derive
the
SCIGROW
estimate.
Small
Scale
Prospective
Groundwater
Monitoring
Study
The
registrant
submitted
a
small
scale
prospective
groundwater
monitoring
study
for
hexazinone
(MRID45132801).
Results
indicated
that
hexazinone
and
its
degradates
are
very
mobile
and
persistent.
As
indicated
earlier,
the
Degradates
D
and
2
(which
were
the
major
degradates
found
in
the
anaerobic
aquatic
metabolism
study),
were
not
monitored
in
the
small
scale
prospective
groundwater
monitoring
studies.
No
information
about
the
fate
of
Degradates
D
and
2
under
natural
environment
is
currently
available.
The
following
table
provides
a
summary
with
the
maximum
concentrations
of
the
parent
and
its
degradates,
detected
in
the
small
scale
prospective
groundwater
monitoring
study.
These
concentrations
(see
column
2)
were
expressed
in
parent
equivalents
(see
Column
3).
The
maximum
total
residues
of
hexazinone
and
its
degradates
detected
in
the
groundwater
study
were
41.8
ppb
(expressed
as
parent
equivalents).
6
Summary
of
Small
Scale
Prospective
Groundwater
Monitoring
Study
Column
1
Column
2
Column
3
Chemical
Maximum
Concentration
in
Groundwater
(ppb)
Maximum
Concentration
in
Groundwater
(ppb,
expressed
as
parent
equivalent)
Parent
9.2
9.2
A
1
(G3453)
3
2.8
B
(A3928)
7.2
7.6
C
(T3935)
1.2
1.1
1
((
JS472)
2.1
2.0
G3170
12.9
19.1
Total
Residues
(parent
equivalent)
Not
applicable
41.8
Concise
Facts
and
Results
About
the
Small
Scale
Prospective
GroundWater
Study
Hexazinone
[Velpar
L,
2
lb
a.
i/
gallon
water
dispersable
liquid]
was
broadcast
applied
once
at
0.75
lb
a.
i./
A
in
January
1996
onto
a
field
of
alfalfa
underlain
with
sandy
soil
in
Merced
County,
California.
The
site
is
located
within
the
recharge
area
for
a
shallow
unconfined
aquifer.
The
treated
area
consisted
of
five
100
x
300
foot
strips
separated
by
irrigation
berms,
and
the
control
area
was
100
feet
distant
and
upgradient
from
the
treated
area.
The
organic
matter
content
of
the
soil
was
#0.7%,
the
pH
was
7.5
8.9
in
the
upper
1.5
feet,
and
there
were
no
continuous
impeding
layers.
The
first
rainfall
was
received
at
7
days
and
the
first
irrigation
event
was
at
75
days.
The
cumulative
net
daily
water
budget
was
<0.0
inches
through
19
days,
0.10
inches
at
21
days,
and
0.93
inches
at
21
days.
The
monthly
cumulative
precipitation
plus
irrigation
ranged
from
111
to
195%
of
baseline.
The
depth
of
the
water
table
ranged
from
8
to
15
feet
below
ground
surface
(bgs)
during
the
study.
Potassium
bromide
was
used
as
a
tracer;
breakthrough
into
the
shallow
groundwater
occurred
at
about
152
days
posttreatment.
Soil
(to
2
feet),
soil
pore
water
(lysimeters
at
3,
6,
9,
and
12
feet),
and
groundwater
(wells
screened
at
14
19
and
20
25
feet
bgs)
samples
were
collected
at
up
to
1063
days
posttreatment
and
analyzed
using
HPLC
for
hexazinone
and
six
transformation
products:
G3170,
A,
B,
C,
A1,
and
1.
Hexazinone
dissipated
from
the
upper
2
feet
of
soil
with
a
calculated
half
life
of
25
days
(r
2
=
0.9997;
first
order
kinetics).
Hexazinone
and
its
degradates
exhibited
a
classic
pattern
of
leaching
through
the
soil
profile
and
into
the
groundwater.
Hexazinone
concentrations
above
background
(-0.05
ppb)
were
first
detected
in
pore
water
at
the
3
foot
depth
at
60
days
posttreatment
and
in
the
6
and
9
foot
7
depths
at
95
days.
The
breakthrough
of
hexazinone
and
degradate
B
into
the
shallow
groundwater
occurred
at
152
days
posttreatment.
G3170
was
the
predominant
degradate
in
the
soil,
soil
pore
water,
and
groundwater;
breakthrough
into
the
shallow
groundwater
occurred
at
336
days.
In
the
individual
shallow
groundwater
wells
(14
19
feet
bgs),
the
maximum
measured
concentrations
were
as
indicated
in
the
table
above.
In
the
individual
deep
groundwater
wells
(20
25
feet
bgs),
the
maximum
measured
concentrations
were
2.33
ppb
for
hexazinone,
2.61
ppb
for
G3170,
1.32
ppb
for
B,
0.952
ppb
for
A1,
and
1.32
ppb
for
C.
The
average
concentrations
of
all
compounds
of
interest
in
the
shallow
and
deep
groundwater
were
below
their
Limit
of
Quantitation
(LOQ
2.0
ppb
except
4.0
ppb
for
C
and
G3170)
in
water,
except
once
at
363
days
when
hexazinone
averaged
2.02
ppb
in
the
shallow
groundwater.
There
was
a
distinct
difference
in
the
movement
of
hexazinone
through
soil
in
the
western
and
eastern
portions
of
the
site.
Hexazinone
residues
were
detected
infrequently
and
at
later
intervals
in
groundwater
in
the
eastern
portion
of
the
site,
where
soils
were
less
sandy
with
thicker
soil
lens.
Surface
Water
and
Ground
Water
Monitoring
Although
this
monitoring
study
was
not
considered
for
the
estimation
of
the
drinking
water
concentrations,
it
is
presented
for
informative
purposes,
since
it
corroborates
some
of
the
conclusions
made
earlier.
The
Board
of
Pesticides
Control
in
the
Department
of
Agriculture,
Food
and
Rural
Resources
in
the
State
of
Maine
conducted
a
statewide
assessment
to
determine
the
impact
of
highly
leachable
pesticides
(including
hexazinone,
an
herbicide
used
in
the
production
of
blueberries)
on
surface
water
and
ground
water
in
Maine.
This
assessment
crossed
a
variety
of
agricultural
and
nonagricultural
pesticide
use
sites.
Surface
water
samples
were
collected
in
Narraguagus
River
and
Pleasant
River
in
Maine.
Groundwater
samples
were
collected
from
the
wells
at
sites
with
the
following
characteristics:
C
they
contain
a
private
domestic
well,
currently
used
for
drinking
water;
C
they
were
within
1/
4
mile
of
an
active
blueberry
field
in
1994;
and
C
they
are
down
gradient
or
of
equal
elevation
with
the
blueberry
field.
Although
the
total
amounts
of
hexazinone
used
on
blueberry
in
Maine
is
very
low
(only
approximately
1%
of
the
total
sale
in
the
U.
S.),
it
was
detected
in
groundwater
and
surface
water
at
very
high
frequency
(43
59%
of
ground
water
samples,
and
31
90%
of
surface
water
samples;
refer
to
table
below).
Although
this
monitoring
study
is
inherently
different
than
the
ground
water
prospective
monitoring
study,
it
was
observed
that
the
maximum
concentrations
of
parent
hexazinone
observed
in
the
ground
waters
in
1998
and
1999
(i.
e.
2.15
and
1.97
ppb,
respectively),
were
similar
to
the
maximum
concentration
observed
in
the
small
scale
ground
water
monitoring
study
(i.
e.
9.2
ppb).
Degradate
B
was
also
detected
in
surface
water
and
groundwater;
however,
no
detailed
information
was
provided.
Results
are
summarized
in
the
following
table.
8
Summary
of
Monitoring
Information
from
the
Board
of
Pesticides
Control
in
the
Department
of
Agriculture,
Food
and
Rural
Resources
in
the
State
of
Maine
Year
No.
of
Samples
Collected
No.
of
Samples
with
Hexazinone
Detected
(%
of
Frequency)
Range
of
Concentrations
(ppb)
Ground
Water
1998
42
18
(43%)
0.14
2.15
1999
22
13
(59%)
0.22
1.97
Surface
Water
1998
36
11
(31%)
0.22
0.94
1999
21
19
(90%)
0.13
3.80
2000
24
21
(88%)
0.13
2.65
2001
50
44
(88%)
0.08
2.45
Modeling
Inputs
and
Results:
The
following
tables
summarize
the
input
values
used
in
the
model
runs
for
FIRST
and
SCIGROW,
respectively.
Fate
parameters
were
obtained
from
studies
submitted
by
the
registrant
and
modified,
if
necessary,
according
to
the
Guidance
for
Selecting
Input
Parameters
in
Modeling
the
Environmental
Fate
and
Transport
of
Pesticides,
Version
Il
(February
28,
2002).
Because
the
half
lives
used
in
the
FIRST
model
are
extremely
long
and
the
chemicals
structures
for
degradates
are
very
similar
to
the
parent
compound
(except
for
G3170),
the
output
values
were
used
to
represent
hexazinone
residues
(including
its
degradates).
9
Environmental
Fate
Input
Parameters
for
FIRST.
Parameter
Hexazinone
Value
Source/
MRID
PC
Code
107201
OPP
Water
Solubility
(20°
C,
distilled
water)
33,000
mg/
L
registrant
Hydrolysis
Half
Life
(pH
7)
Stable
41587301
Aerobic
Soil
Metabolism
Half
Life
216x3=
648
days
41807401;
42635001
Aerobic
Aquatic
Metabolism
Half
Life
60x3=
180
days
41811801
Aqueous
Photolysis
Half
Life
(at
pH
7)
Stable
41300801
Soil
Water
Partition
Coefficient
(Kd)
0.45
41528101
Pesticide
is
Wetted
In
No
label
PCA
0.87
OPP
Depth
of
Incorporation
(Aerial)
0.0
Label
Environmental
Fate
Input
Parameters
for
SCIGROW.
Parameter
Hexazinone
Value
Source
(MRID)
Organic
Carbon
Partition
Coefficient
(KOC)
37
41528101
Aerobic
Soil
Metabolism
Half
Life
216
days
41807401;
42635001
Application
Information
and
Modeling
Results
for
Use
of
Hexazinone
on
Alfalfa.
Parameter
Hexazinone
value
Source
Crop
Alfalfa
label
Application
Method
Aerial
spray
label
Application
Rate
1.5
lbs
a.
i/
acre
label
Application
Frequency
once/
year
label
Incorporation
Depth
0
inches
lbel
Application
Interval
(days)
N/
A
label
10
The
modeling
results
associated
with
maximum
allowable
rate
per
year
for
representative
crops
are
presented
in
the
following
table.
Attached
to
this
memo
(Appendix
1)
are
copies
of
the
original
printouts
generated
from
FIRST
and
SCIGROW
runs.
In
addition,
the
chemical
structures
of
Hexazinone
and
its
major
degradation
products
are
presented
in
Appendix
2.
Modeling
Results
Model
Hexazinone
value
Source
FIRST
1.0
Peak
Untreated
Water
Concentration
129.8
ppb
Output
FIRST
1.0
Annual
Average
Untreated
Water
Concentration
47.1
ppb
Output
SCI
GROW
Ground
Water
Concentration
20.2
ppb
Output
11
Appendix
1.
Printouts
of
Electronic
Outputs
Obtained
from
FIRST
and
SCIGROW
With
Use
of
Hexazinone
on
Alfalfa
at
1.5
lb
a.
i./
A
FIRST
run
RUN
No.
200
FOR
hexazinone
ON
alfalfa
*
INPUT
VALUES
*
RATE
(#/
AC)
No.
APPS
&
SOIL
SOLUBIL
APPL
TYPE
%CROPPED
INCORP
ONE(
MULT)
INTERVAL
Kd
(PPM
)
(%
DRIFT)
AREA
(IN)
1.500(
1.500)
1
1
.4
30000.0
AERIAL(
16.0)
87.0
.0
FIELD
AND
RESERVOIR
HALFLIFE
VALUES
(DAYS)
METABOLIC
DAYS
UNTIL
HYDROLYSIS
PHOTOLYSIS
METABOLIC
COMBINED
(FIELD)
RAIN/
RUNOFF
(RESERVOIR)
(RES.
EFF)
(RESER.)
(RESER.)
648.00
2
N/
A
.00
.00
180.00
180.00
UNTREATED
WATER
CONC
(MICROGRAMS/
LITER
(PPB))
Ver
1.0
AUG
1,
2001
PEAK
DAY
(ACUTE)
ANNUAL
AVERAGE
(CHRONIC)
CONCENTRATION
CONCENTRATION
129.789
47.139
SCIGROW
run
RUN
No.
300
FOR
hexazinone
INPUT
VALUES
APPL
(#/
AC)
APPL.
URATE
SOIL
SOIL
AEROBIC
RATE
NO.
(#/
AC/
YR)
KOC
METABOLISM
(DAYS)
1.500
1
1.500
37.0
216.0
GROUND
WATER
SCREENING
CONCENTRATIONS
IN
PPB
20.177970
A=
211.000
B=
42.000
C=
2.324
D=
1.623
RILP=
5.524
F=
1.129
G=
13.452
URATE=
1.500
GWSC=
20.177970
A=
211.000
B=
55.000
C=
2.324
D=
1.740
RILP=
5.252
F=
.963
G=
9.178
URATE=
1.500
GWSC=
13.766800
12
N
N
N
O
O
CH
3
N(
CH
3
)
2
S
N
N
N
O
O
CH
3
N(
CH
3
)
2
HO
S
N
N
N
O
O
CH
3
N(
CH
3
)
2
OH
S
Appendix
2.
Chemical
Structures
of
Hexazinone
and
its
Major
Metabolites
Nomenclature
for
the
Degradates
Structure
of
Hexazinone,
A3674
Metabolite
A,
T3937
Metabolite
A1,
G3453
13
N
N
N
O
O
CH
3
NHCH
3
S
N
N
N
O
O
CH
3
N(
CH
3
)
2
O
Metabolite
C,
T3935
Metabolite
B,
A3928
Metabolite
1,
JS472
14
N
N
N
O
OH
CH
3
N(
CH
3
)
2
IN
G3170
Nomenclature:
Metabolite
A,
T3937
3(
4
hydroxycyclohexyl)
6(
demethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
Metabolite
A1,
G3453
3(
2
hydroxycyclohexyl)
6(
demethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
Metabolite
C,
T3935
3(
4
hydroxycyclohexyl)
6(
methylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
Metabolite
B,
A3928
3
cyclohexyl
6(
methylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
Metabolite
1,
JS472
3(
4
ketocyclohexyl)
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
IN
G3170,
N
Demethyl
B3170
6(
methylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
| epa | 2024-06-07T20:31:42.864104 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0011/content.txt"
} |
EPA-HQ-OPP-2002-0188-0012 | Supporting & Related Material | "2002-09-16T04:00:00" | null | TXR#
0050775
TXR#
0050775
May
30,
2002
May
30,
2002
OFFICE
OF
PREVENTION,
PESTICIDES
AND
MEMORANDUM:
TOXIC
SUBSTANCES
Subject:
107201:
The
Toxicology
Chapter
for
the
TRED
for
Hexazinone.
DP
Barcode:
D275620
Submission:
S598837
ReReg
Case#
0266
CAS#:
51235
04
02
From:
David
G
Anderson
RRB
2
HED
(7509C)
To:
Carol
Christensen,
Risk
Assessor
RRB
2
HED
(7509C)
Thru:
Alan
Nielsen,
BSS
RRB
2,
HED
(7509C)
cc
Pauline
Wagner
The
Toxicology
Chapter
for
the
Tolerance
Reassessment
Evaluation
Decision
(TRED)
for
Hexazinone
is
attached.
1
Hexazinone
PC
Code:
107201
Toxicology
Disciplinary
Chapter
for
the
Tolerance
Reassessment
Evaluation
Decision
Document
Date
completed:
May
16,
2002
Prepared
for:
Health
Effects
Division
Office
of
Pesticide
Programs
U.
S.
Environmental
Protection
Agency
Arlington,
VA
22202
Prepared
by:
David
G
Anderson
form:
FINAL
June
21,
2000
2
TABLE
OF
CONTENTS
1.0
HAZARD
CHARACTERIZATION
........................................
3
2.0
REQUIREMENTS
.....................................................
4
3.0
DATA
GAP(
S)
........................................................
5
4.0
HAZARD
ASSESSMENT
...............................................
5
4.1
Acute
Toxicity
...................................................
5
4.2
Subchronic
Toxicity
...............................................
5
4.3
Prenatal
Developmental
Toxicity
......................................
8
4.4
Reproductive
Toxicity
............................................
11
4.5
Chronic
Toxicity
.................................................
13
4.6
Carcinogenicity
.................................................
14
4.7
Mutagenicity
...................................................
18
4.8
Neurotoxicity
...................................................
21
4.9
Metabolism
....................................................
22
4.10
Special/
Other
Studies
.............................................
23
5.0
TOXICITY
ENDPOINT
SELECTION
....................................
23
5.1
See
Section
9.2
for
Endpoint
Selection
Table.
...........................
23
5.2
Dermal
Absorption
...............................................
23
5.3
Classification
of
Carcinogenic
Potential
................................
23
6.0
FQPA
CONSIDERATIONS
............................................
24
6.1
Special
Sensitivity
to
Infants
and
Children
..............................
24
6.2
Recommendation
for
a
Developmental
Neurotoxicity
Study
.................
24
7.0
OTHER
ISSUES
......................................................
24
8.0
REFERENCES
.......................................................
24
Other
references
......................................................
27
9.0
APPENDICES
.....................................................
28
9.1
Toxicity
Profile
Summary
Tables
.....................................
29
9.1.1
Acute
Toxicity
Table
.......................................
29
9.1.2
Subchronic,
Chronic
and
Other
Toxicity
Tables
...................
29
9.2
Summary
of
Toxicological
Dose
and
Endpoints
..........................
34
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
3
1.0
HAZARD
CHARACTERIZATION
Hexazinone
is
a
herbicide
used
to
control
a
broad
spectrum
of
weeds
including
woody
plants
in
alfalfa,
rangeland,
pastures,
woodlands,
pineapple,
sugarcane
and
blue
berries.
Non
crop
areas
include
ornamental
plants
and
forests.
Hexazinone
is
used
as
a
pre
emergent,
post
emergence
herbicide.
It
is
applied
by
direct
spray
to
plants
and
to
soils.
There
are
no
non
occupational
(residential)
uses.
Hexazinone
is
a
triazine
herbicide,
which
structurally
dissimilar
and
toxicology
different
from
other
triazines,
such
as
atrazine.
The
selectivity
of
triazine
herbicides
depends
on
the
plant's
ability
to
degrade
or
metabolize
the
parent
compound.
Sensitive
plants
have
limited
ability
to
metabolize
hexazinone.
Hexazinone
acts
through
inhibition
of
photosynthesis.
Hexazinone
has
low
acute
toxicity
by
the
oral
(Category
III),
dermal
(Category
IV
)
and
inhalation
routes
(Category
III).
Primary
eye
irritation
is
severe,
causing
corneal
opacity
and
moderate
irritation
in
unwashed
eyes
(Category
I).
It
causes
mild
skin
irritation
and
is
classified
Category
IV
for
skin
irritation.
It
is
not
a
skin
sensitizer
in
the
Guinea
pig.
The
21
day
dermal
study
in
the
rabbit
showed
no
systemic
toxicity
and
mild
dermal
irritation
at
the
limit
dose.
Body
weight
decrement
and
liver
toxicity
were
the
most
frequent
effects
shown
in
studies
with
hexazinone.
Liver
toxicity
was
seen
in
the
chronic
dog
and
mouse
studies.
Body
weight
decrement
was
seen
in
the
chronic
rat
studies
and
the
studies
on
reproduction.
No
quantitative
or
qualitative
susceptibility
was
shown
in
the
prenatal
or
reproduction
studies.
In
a
reproduction
study,
pup
weight
decrement
occurred
at
the
same
dose
as
parental
body
weight
decrement.
No
reproductive
effects
were
seen
in
the
study
other
than
pup
weight
decrement.
The
rat
prenatal
study
showed
fetal
weight
decrement
and
possibly
renal
malformations
but
no
increased
susceptibility.
The
rabbit
study
possibly
showed
skeletal
anomalies
and
delayed
ossifications
at
the
highest
dose
tested,
however
it
is
classified
as
unacceptable
and
susceptibility
in
this
species
could
not
be
assessed.
The
chronic
study
in
dogs
showed
severe
body
weight
decrement,
changes
in
liver
related
clinical
chemistry
values,
and
microscopic
lesions.
Body
weight
decrement
was
seen
in
a
chronic
carcinogenicity
studies
in
rats
and
mice.
Liver
toxicity
was
seen
in
mice.
The
mouse
carcinogenicity
study
showed
an
increased
trend
for
liver
carcinomas,
but
no
pair
wise
significant
increases.
The
rat
study
showed
no
carcinogenic
potential.
Based
on
these
studies
in
rats
and
mice,
hexazinone
was
classified
in
a
group
D,
not
classifiable
as
a
carcinogen.
Hexazinone
is
clastogenic
in
one
in
vitro
test
for
chromosomal
aberrations,
but
negative
in
the
remaining
six
other
mutagenicity
studies
including
an
in
vivo
micronucleus
test
in
mouse
bone
marrow.
Rat
metabolism
studies
showed
that
hexazinone
was
rapidly
absorbed
and
excreted
and
essentially
no
difference
in
the
metabolism
of
males
and
females
at
high
or
low
dose
levels.
Almost
no
parent
hexazinone
was
recovered
in
urine
or
feces.
Two
major
metabolites
were
recovered
from
feces
and
urine,
in
addition
to
lesser
amounts
of
a
third
metabolite
and
individually
small
amounts
of
conjugated
products
from
urine.
The
HIARC
requested
a
28
day
inhalation
study
with
hexazinone
because
of
the
concern
for
potential
inhalation
exposure
based
on
the
use
pattern.
The
rabbit
developmental
toxicity
study
is
classified
as
unacceptable.
A
10X
uncertainty
factor
was
applied
until
this
data
gap
is
fulfilled.
Another
study
in
the
rabbit,
requested
by
Cal
EPA,
is
expected
to
be
submitted
to
OPP
as
well.
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
4
2.0
REQUIREMENTS
The
requirements
(40
CFR
158.340)
for
food
and
non
food
use
for
HEXAZINONE
are
in
Table
1.
Use
of
the
new
guideline
numbers
does
not
imply
that
the
new
(1998)
guideline
protocols
were
used.
Table
1.
Test
Technical
Required
Satisfied
870.1100
Acute
Oral
Toxicity
..............................
870.1200
Acute
Dermal
Toxicity
............................
870.1300
Acute
Inhalation
Toxicity
.........................
870.2400
Primary
Eye
Irritation
.............................
870.2500
Primary
Dermal
Irritation
..........................
870.2600
Dermal
Sensitization
..............................
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
870.3100
Oral
Subchronic
(rodent)
..........................
870.3150
Oral
Subchronic
(nonrodent)
......................
870.3200
21
Day
Dermal
...................................
870.3250
90
Day
Dermal
...................................
870.3465
90
Day
Inhalation
................................
Yes
Yes
Yes
No
1
No
2
Yes
Yes
Yes
Yes
No
870.3700a
Developmental
Toxicity
(rodent)
...................
870.3700b
Developmental
Toxicity
(nonrodent)
...............
870.3800
Reproduction
...................................
Yes
Yes
Yes
Yes
No
3
Yes
870.4100a
Chronic
Toxicity
(rodent)
.........................
870.4100b
Chronic
Toxicity
(nonrodent)
......................
870.4200a
Oncogenicity
(rat)
...............................
870.4200b
Oncogenicity
(mouse)
............................
870.4300
Chronic/
Oncogenicity
...........................
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
870.5100
Mutagenicity—
Gene
Mutation
bacterial
...........
870.5300
Mutagenicity—
Gene
Mutation
mammalian
.........
870.5xxx
Mutagenicity—
Structural
Chromosomal
Aberrations
.
870.5xxx
Mutagenicity—
Other
Genotoxic
Effects
............
Yes
Yes
Yes
Yes
No
Yes
Yes
Yes
870.6100a
Acute
Delayed
Neurotox.
(hen)
....................
870.6100b
90
Day
Neurotoxicity
(hen)
........................
870.6200a
Acute
Neurotox.
Screening
Battery
(rat)
............
870.6200b
90
Day
Neuro.
Screening
Battery
(rat)
..............
870.6300
Develop.
Neuro
..................................
No
4
No
4
No
5
No
5
No
5
870.7485
General
Metabolism
..............................
870.7600
Dermal
Penetration
..............................
Yes
No
6
Yes
No
Special
Studies
for
Ocular
Effects
7
Acute
Oral
(rat)
..................................
Subchronic
Oral
(rat)
.............................
Six
month
Oral
(dog)
.............................
1
Study
not
required
by
use
pattern.
2
A
28
day
inhalation
study
was
recommended
by
the
HIARC
and
is
required.
3
Data
gap,
another
rabbit
developmental
toxicity
is
required
4
Required
of
organophosphates
only.
5
Not
required
by
toxicity
pattern.
6
Study
is
optional.
7
Not
required
for
this
class
of
pesticides.
3.0
DATA
GAP(
S)
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
5
1.
28
Day
Inhalation
Study
(Contact
Agency
before
conducting
test)
2.
A
Rabbit
Developmental
Toxicity
Study
is
required
(Guideline#
870.3700b)
4.0
HAZARD
ASSESSMENT
4.1
Acute
Toxicity
Adequacy
of
data
base
for
acute
toxicity:
The
data
base
for
acute
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
The
acute
toxicity
data
on
HEXAZINONE
technical
is
summarized
below.
Acute
Toxicity
of
Hexazinone
Guideline
No.
Study
Type
MRIDs
#
Results
Toxicity
Category
81
1
Acute
Oral/
Rat
41235004
(1989)
LD50
=
1200
mg/
kg
III
81
2
Acute
Dermal/
Rabbit
00104974
LD50
>5278
mg/
kg
IV
81
3
Acute
Inhalation
41756701
(1991)
LC50
>
3.94
mg/
L(
4
hour)
III
81
4
Primary
Eye
Irritation
00106003
(1982)
Irreversible
corneal
opacity,
Severe
I
81
5
Primary
Skin
Irritation
00106004
(1982)
Mild
IV
81
6
Dermal
Sensitization
41235005
(1989)
NA
Not
a
skin
sensitizer
4.2
Subchronic
Toxicity
Adequacy
of
data
base
for
subchronic
toxicity:
The
data
base
for
subchronic
toxicity
is
considered
adequate
for
reregistration.
Only
a
28
day
inhalation
study
is
required
at
this
time.
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
6
870.3100
90
Day
Oral
Toxicity
Rat
EXECUTIVE
SUMMARY:
In
this
subchronic
oral
toxicity
study
(MRID
00104977),
hexazinone
(INA
3674;
purity
not
provided;
Lot/
Batch
#
not
provided)
was
administered
in
the
diet
to
16
ChRCD
rats/
sex/
group
at
nominal
doses
of
0,
200,
1000,
or
5000
ppm
(equivalent
to
0/
0,
16.0/
16.4,
81.0/
87.3,
or
440.4/
450.7
mg/
kg
for
males/
females)
for
13
weeks.
After
4,
8,
and
13
weeks
on
the
test
diet,
10
of
the
16
rats/
sex/
dose
were
subjected
to
hematology,
clinical
chemistry,
and
urinalysis
tests.
After
13
weeks,
10
rats/
sex/
group
were
sacrificed
for
necropsy
and
histopathological
examination.
The
remaining
6
rats/
sex/
group
continued
on
the
test
diet
for
at
least
3
weeks
in
a
onegeneration
one
litter
reproduction
study.
There
were
no
treatment
related
effects
on
mortality,
clinical
signs,
food
consumption,
hematology,
urinalysis,
organ
weights,
or
histopathology.
No
data
were
provided
for
gross
pathology.
In
the
200
and
1000
ppm
animals,
all
parameters
examined
were
comparable
to
controls.
Body
weights
were
decreased
in
the
5000
ppm
animals
(94
15%)
throughout
the
study.
Likewise,
overall
body
weight
gains
(calculated
by
the
reviewers)
were
decreased
in
this
group
(98
20%).
Although
food
consumption
was
comparable
among
treated
animals
and
controls,
overall
(Days
0
91)
mean
food
efficiency
was
decreased
(statistics
not
performed)
in
the
5000
ppm
males
(911%)
and
females
(915%)
compared
to
controls.
Food
efficiency
in
males
and
females
was
unchanged
for
the
first
28
days
of
the
study.
Males
showed
a
6%
and
9%
decrement
for
days
28
56
and
days
56
91,
respectively
at
5000
ppm.
Females
showed
a
25%
and
64%
decrement
in
food
efficiency
for
the
same
respective
days.
The
progressive
nature
of
the
reduced
food
efficiency,
especially
in
females,
supports
a
body
weight
decrement
at
5000
ppm
from
toxicity.
Alanine
aminotransferase
(ALT)
was
increased
(statistics
not
performed)
in
the
5000
ppm
females
at
1
(863%),
2
(863%),
and
3
(825%)
months.
However,
because
there
were
no
treatmentrelated
changes
in
liver
weights
or
histology,
increases
in
ALT
were
considered
of
equivocal
toxicological
significance.
For
all
other
clinical
chemistry
parameters
examined,
treatment
groups
were
either
comparable
to
controls,
sporadic,
or
differences
were
not
dose
related.
Additionally,
in
the
one
generation,
one
litter
reproduction
study,
there
were
no
treatmentrelated
differences
in
pregnancy
rate
(fertility),
gestation,
number
of
pups
born,
pup
viability,
or
lactation.
However,
the
mean
pup
weight
was
lower
(924%;
statistics
not
performed)
in
the
5000
ppm
group
than
in
controls.
The
LOAEL
for
this
study
is
5000
ppm
(equivalent
to
440.4/
450.7
mg/
kg/
day
for
male/
females)
based
on
decreased
body
weights
and
food
efficiency.
The
NOAEL
is
1000
ppm
(equivalent
to
81.0/
87.3
mg/
kg/
day
for
males/
females).
The
submitted
study
is
classified
as
acceptable
does
satisfy
the
guideline
(§
82
1a;
OPPTS
870.3100)
requirements
for
a
subchronic
oral
toxicity
study
in
the
rat.
870.3100
90
Day
Oral
Toxicity
Mouse
No
study
is
available.
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
7
870.3150
90
Day
Oral
Toxicity
Dog
EXECUTIVE
SUMMARY:
In
this
subchronic
oral
study
(MRID
00114484),
hexazinone
INA3674
97.5%
a.
i.;
Lot/
Batch#
not
provided)
was
administered
in
the
diet
to
4
beagle
dogs/
sex/
group
at
doses
of
0,
200,
1000,
or
5000
ppm
(equivalent
to
0/
0,
5.1/
7.0,
25.9/
31.6,
122.5/
137.3
mg/
kg/
day
for
males/
females)
for
13
weeks.
Homogeneity,
concentration,
and
stability
analyses
were
not
performed
on
the
test
diets.
No
mortalities
occurred
during
the
study.
Clinical
signs
and
hematology
were
unaffected
by
the
test
substance.
At
5000
ppm,
the
negative
overall
(Weeks
0
13)
body
weight
gains
show
that
these
animals
were
unable
to
maintain
body
weight
(
0.9
kg
in
males,
0.3
kg
in
females).
Food
consumption
was
decreased
in
the
females
in
this
dose
group
at
Weeks
1
(941%)
and
2
(915%).
In
the
males,
food
consumption
was
comparable
among
treated
and
control
groups
throughout
the
study.
Findings
in
organ
weights
and
clinical
chemistry
at
5000
ppm
indicate
liver
toxicity
as
an
effect
of
treatment.
Absolute
liver
weights
were
increased
in
the
males
at
200
(810%),
1000
(821%),
and
5000
(826%)
ppm
and
in
the
females
at
5000
(833%)
ppm.
However,
relative
liver
weights
were
only
increased
at
5000
ppm
in
the
males
(827%)
and
females
(840%),
indicating
the
increases
in
absolute
liver
weights
at
200
and
1000
ppm
were
most
likely
due
to
increased
body
weights
in
these
animals
compared
to
controls.
Alkaline
phosphatase
levels
were
increased
in
the
males
and
females
in
this
dose
group
at
1
(846
75%),
2
(886
125%),
and
3
(8124
214%)
months.
Serum
levels
of
this
enzyme
increased
as
the
study
progressed.
In
the
5000
ppm
males,
proteinuria
was
observed
at
Months
2
and
3
(1/
4
each
treated
vs
0/
4
in
any
other
dose
group).
Vacuolation
of
the
cytoplasm
of
the
cells
lining
the
Loop
of
Henle
was
observed
in
the
males
(1/
4
treated
vs
0/
4
controls)
and
females
(1/
4
treated
vs
0/
4
controls)
in
this
dose
group.
The
LOAEL
was
5000
ppm
(equivalent
to
122.5/
137.3
mg/
kg/
day
in
males/
females)
based
on
decreased
body
weight
gains,
increased
relative
liver
weights,
and
increased
alkaline
phosphatase
levels
in
both
sexes
and
transiently
decreased
food
consumption
in
the
females.
The
NOAEL
for
this
study
is
1000
ppm
(equivalent
to
25.9/
31.6
mg/
kg/
day
for
males/
females).
The
submitted
study
is
classified
as
acceptable
and
does
satisfy
the
guideline
(§
82
1b;
OPPTS
870.3150)
requirement
for
a
subchronic
oral
toxicity
study
in
the
dog.
The
deficiencies
in
the
parameters
reported
did
not
appear
to
compromise
the
study
results.
870.3200
21/
28
Day
Dermal
Toxicity
–
Rat
EXECUTIVE
SUMMARY:
In
a
repeated
dose
dermal
toxicity
study
(MRID
41309005),
groups
of
five
male
and
five
female
New
Zealand
White
rabbits
received
applications
of
0,
50,
400,
or
1000
mg/
kg/
day
Hexazinone
technical
(>
98%,
Lot
No.
T02118994)
in
distilled
water,
6
hours/
day
for
21
consecutive
days.
There
were
no
treatment
related
deaths,
clinical
signs,
hematological
or
clinical
chemistry
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
8
effects,
organ
weight
effects
or
gross
or
histopathological
effects
attributable
to
treatment.
No
treatment
related
body
weight,
food
consumption,
or
food
efficiency
effects
were
observed.
Treatment
related
dermal
irritation
was
observed
on
rabbits
in
all
treatment
groups,
including
controls.
Slight
erythema
was
noted
on
3/
5
control
females,
4/
5
low
dose
males,
4/
5
low
dose
females,
and
all
mid
and
high
dose
males
and
females.
Slight
edema
was
noted
on
1/
5
control
female,
1/
5
high
dose
male,
and
1/
5
high
dose
female.
These
dermal
effects
were
not
considered
toxicologically
significant.
The
systemic
and
dermal
NOAEL
for
Hexazinone
technical
in
male
and
female
rabbits
is
the
limit
dose
of
1000
mg/
kg/
day.
The
systemic
and
dermal
LOAEL
were
not
identified.
This
study
is
classified
as
Acceptable/
Guideline
and
does
satisfy
the
guideline
requirements
for
a
repeated
dose
dermal
study
[OPPTS
870.3200
(§
82
2)]
in
rabbits.
870.3465
90
Day
Inhalation
–
Rat
No
study
is
available.
The
HIARC
determined
that
a
28
day
inhalation
study
is
required
to
address
the
concern
for
inhalation
exposure
due
in
part
to
the
irritating
properties
of
hexazinone.
The
Agency
should
be
contacted
prior
to
conducting
this
study.
4.3
Prenatal
Developmental
Toxicity
Adequacy
of
data
base
for
Prenatal
Developmental
Toxicity:
The
data
base
for
prenatal
developmental
toxicity
is
not
complete.
The
HIARC
declared
the
Rabbit
developmental
toxicity
study
unacceptable/
upgradable.
Another
study
is
required.
There
was
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
following
in
utero
exposure
to
the
acceptable
rat
study
or
the
unacceptable
rabbit
study.
In
rats,
maternal
toxicity
was
seen
at
a
lower
dose
than
developmental
toxicity,
and
in
rabbits,
developmental
effects
may
have
been
at
the
same
dose
level
as
maternal
toxicity.
870.3700a
Prenatal
Developmental
Toxicity
Study
Rat
EXECUTIVE
SUMMARY:
In
a
developmental
toxicity
study
(MRID
40397501),
hexazinone
(99.26%
a.
i.;
Lot#
S30306A,
Batch#
2/
36)
in
0.5%
methylcellulose
was
administered
orally
via
gavage
to
25
Crl:
CD
®
BR
female
rats/
group
at
dose
levels
of
0,
40,
100,
400,
or
900
mg/
kg
on
gestation
day
(GD)
7
through
16.
The
dosing
volume
was
10
mL/
kg
(calculated
by
reviewers).
All
dams
were
sacrificed
on
GD
22
and
their
fetuses
removed
by
cesarean
and
examined.
When
compared
to
concurrent
controls,
no
treatment
related
changes
in
clinical
signs,
gross
pathology,
pregnancy
rate,
live
fetuses,
resorptions,
pre
or
post
implantation
loss,
corpora
lutea,
or
implantations
were
noted
at
any
dose
level
tested.
No
treatment
related
findings
were
noted
in
the
100,
or
40
mg/
kg
groups.
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
9
In
the
900
mg/
kg
dams,
one
treatment
related
death
occurred;
alopecia
and
an
enlarged
stomach
containing
fluid
and
food
were
noted
at
necropsy.
Decreased
(p<
0.05)
body
weight
gains
were
noted
during
GDs
15
17
(937%)
and
17
22
(917%).
In
addition,
body
weight
gains
were
decreased
(p<
0.05)
for
the
overall
(GDs
7
17)
treatment
interval
(930%).
Gravid
uterine
weights
were
not
reported;
however,
adjusted
(for
gravid
uterine
weight)
terminal
body
weights
were
slightly
decreased
(96%;
p#0.05).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
GDs
9
11,
15
17,
7
17,
and
17
22.
Decreased
(p#0.05)
food
consumption
was
observed
throughout
treatment
(GDs
7
17;
916
22%)
and
post
treatment
(GDs
17
22;
99%).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
GDs
7
9,
9
11,
11
13,
13
15,
15
17,
7
17,
and
17
22.
Also
a
significantly
decreased
food
consumption
was
seen
at
400
mg/
kg/
day
(GD9
11;
91%)
and
(GD
7
17;
98%).
In
addition,
relative
(to
body)
liver
weights
were
increased
(p#0.05)
in
the
400
(5.2%)
and
900
(5.6%)
mg/
kg
dams
compared
to
concurrent
controls
(4.9%).
Decreased
(p#0.05)
terminal
body
weights
were
noted
at
900
mg/
kg
(96%).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
relative
liver
weights
and
adjusted
terminal
body
weights.
In
addition,
a
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
absolute
liver
weights.
Despite
this
trend,
the
observed
increases
in
absolute
liver
weights
at
100,
400,
and
900
mg/
kg
(81
8%)
were
not
statistically
significant.
Liver
weight
findings
are
considered
equivocal.
The
maternal
LOAEL
is
400
mg/
kg/
day
based
on
decreased
food
consumption
during
dosing
and
nominal
decreases
in
body
weight
gain
from
day
7
to
day
17
and
at
all
measured
intervals
between
and
at
900
mg/
kg/
day
on
mortality
and
decreased
body
weight
gains
and
food
consumption.
The
maternal
NOAEL
is
100
mg/
kg/
day.
In
the
900
mg/
kg/
day
group,
male
and
female
fetal
weights
were
decreased
(921%;
p#0.05);
a
significant
(p#0.05)
trend
by
Jonckheere's
test
was
noted
for
this
parameter.
At
400
mg/
kg/
day,
only
female
fetal
weights
were
significantly
decreased
by
2%
(insufficient
to
be
considered
an
effect).
At
necropsy,
an
increased
(p#0.05)
incidence
of
misaligned
sternebrae
(1),
a
variation,
was
observed
(fetal
incidence:
0.0217;
litter
incidence:
0.30)
relative
to
concurrent
controls
(fetal
incidence:
0.0066;
litter
incidence:
0.09).
In
addition,
an
increased
(p#0.05)
incidence
of
misaligned
sternebrae
(2+),
a
variation,
was
noted
(fetal
incidence:
0.0217;
litter
incidence:
0.30)
relative
to
concurrent
controls
(fetal
incidence:
0.0033;
litter
incidence:
0.04).
Furthermore,
an
increased
incidence
of
kidneys
with
no
papilla
was
observed
(fetal
incidence:
0.0347;
litter
incidence:
0.25)
relative
to
concurrent
controls
(fetal
incidence:
0.0062;
litter
incidence:
0.04).
Although
the
incidence
was
not
statistically
significant,
a
dose
related
trend
(p#0.05)
was
observed.
The
developmental
toxicity
LOAEL
is
900
mg/
kg/
day
based
on
decreased
male
and
female
fetal
weight,
increased
incidence
of
kidneys
with
no
papilla
(malformation),
and
an
increased
incidence
of
misaligned
sternebrae
(variation).
The
developmental
toxicity
NOAEL
is
400
mg/
kg/
day.
The
developmental
toxicity
study
in
the
rat
is
classified
acceptable/
guideline
(OPPTS
870.3700;
§83
3
a)
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
in
the
rat.
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
10
870.3700a
Prenatal
Developmental
Toxicity
Study
Rat
EXECUTIVE
SUMMARY:
In
a
developmental
toxicity
study
(MRID
00114486),
hexazinone
(97.5%
a.
i.;
Code#
INA
3674
19,
Lot/
Batch#
N.
B.
6849
30
[6842
29];
no
further
information
provided)
was
administered
orally
in
the
diet
to
25
27
ChR
CD
female
rats/
group
at
dose
levels
of
0,
200,
1000,
or
5000
ppm
(equivalent
to
0,
18.9,
94.5,
and
482.0
mg/
kg)
on
GD
6
through
15.
All
dams
were
sacrificed
on
GD
21
and
their
fetuses
removed
by
cesarean
and
examined.
When
compared
to
concurrent
controls,
no
treatment
related
changes
in
food
consumption,
or
number
of
implantations,
live
fetuses,
dead
fetuses,
or
premature
deliveries
were
noted.
It
was
stated
that
no
treatment
related
changes
in
mortality,
clinical
signs,
or
gross
pathology
were
observed;
however
no
data
were
provided.
Gravid
uterine
weights
were
not
reported.
Sex
ratios,
the
number
of
corpora
lutea,
pre
implantation
loss,
and
post
implantation
loss
were
not
reported
and
could
not
be
calculated
without
individual
data
(not
provided).
Throughout
the
study,
standard
deviations
were
not
calculated,
individual
data
were
not
provided,
and
statistical
analyses
were
not
performed.
Mean
body
weight
gains
and
food
efficiency
were
decreased
during
treatment
(GDs
6
16).
At
5000
ppm,
mean
body
weight
gains
were
decreased
by
74%
compared
to
concurrent
controls.
In
addition,
food
efficiency
during
the
treatment
interval
was
0.84
(vs.
3.0
in
controls).
At
5000
ppm,
markedly
decreased
body
weights
were
observed
at
GDs
16
(919%)
and
21
(912%).
Additionally
at
5000
ppm,
the
number
of
females
showing
partial
resorption
(excluding
complete
resorptions)
was
56.5%.
This
incidence
exceeded
the
concurrent
control
incidence
(39.1%);
however,
it
was
within
the
range
of
historical
controls
(mean
was
40.6%,
range
was10.5
77.8%).
The
maternal
LOAEL
is
5000
ppm
(equivalent
to
482
mg/
kg/
day)
based
on
decreased
body
weights,
body
weight
gains,
and
food
efficiency.
The
maternal
NOAEL
is
1000
ppm
(equivalent
to
94.5
mg/
kg/
day).
No
treatment
related
findings
were
noted
in
the
fetuses
at
200,
1000,
or
5000
ppm.
The
developmental
toxicity
LOAEL
was
not
observed.
The
developmental
toxicity
NOAEL
is
5000
ppm
(equivalent
to
482.0
mg/
kg/
day).
This
developmental
toxicity
study
in
the
rat
is
classified
unacceptable/
upgradable
pending
submission
of
the
following
information:
Individual
maternal
and
fetal
data
Statistical
analyses
of
the
data
Environmental
conditions
of
the
testing
laboratory
Gross
pathology
data.
Sex
ratios,
the
number
of
corpora
lutea,
pre
implantation
loss,
and
post
implantation
loss
Litter
incidence
for
fetal
necropsy
findings
Clinical
signs
and
mortality
data
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
11
870.3700b
Prenatal
Developmental
Toxicity
Study
Rabbit
EXECUTIVE
SUMMARY:
In
a
developmental
toxicity
study
(MRID
00028863),
hexazinone
(100%
a.
i.;
Lot/
batch
#
E21216A)
was
administered
orally
via
gavage
in
a
dosing
volume
of
1
mL/
kg)
to
17
female
New
Zealand
White
rabbits/
group
at
dose
levels
of
0,
20,
50,
or
125
mg/
kg
on
GD
6
through
19.
All
does
(except
those
that
died
or
delivered
prematurely)
were
sacrificed
on
GD
29,
and
their
fetuses
removed
by
cesarean
and
examined.
When
compared
to
concurrent
controls,
no
treatment
related
changes
in
mortality,
clinical
signs,
body
weights,
gross
pathology,
fetal
weights,
sex
ratios,
pre
implantation
or
post
implantation
losses,
or
the
number
of
corpora
lutea,
implantations,
resorptions,
live
fetuses,
or
dead
fetuses
were
observed.
At
125
mg/
kg,
food
consumption
was
decreased
(p#0.05),
relative
to
concurrent
controls,
at
the
beginning
of
treatment
from
GD
7
through
11
(961
89%).
Decreases
in
food
consumption,
that
were
not
statistically
significant,
continued
throughout
treatment
(GDs
12
19;
92
37%).
Diminished
food
consumption
resulted
in
decreased
(not
statistically
significant)
body
weight
gains
in
the
does
241.5
g)
relative
to
concurrent
controls
(
7.2
g)
during
GDs
6
11.
However,
weight
gain
in
these
animals
recovered
quickly
and
was
higher
than
control
animals
during
subsequent
treatment
intervals
(GDs
11
15
and
15
19).
The
maternal
LOAEL
is
125
mg/
kg/
day
based
on
transient
decreases
in
food
consumption
and
body
weight
gains.
The
maternal
NOAEL
is
50
mg/
kg/
day.
At
125
mg/
kg/
day,
the
following
skeletal
variations
were
noted
(data
presented
as
fetal
incidence
vs.
0
controls):
(i)
lagging
ossification
in
extremities
(0.0882);
(ii)
malaligned
thoracic
vertebrae
(0.0294);
and
(iii)
flexed
wrist(
s)
(0.0294).
In
addition,
non
ossified
thumb,
an
anomaly,
was
noted
at
an
increased
incidence
(0.0294)
relative
to
concurrent
controls
(0).
In
the
absence
of
historical
control
data,
these
findings
are
considered
treatment
related.
In
addition,
it
could
not
be
determined
how
many
of
these
nominally
increased
incidences
were
from
different
litters,
which
would
have
increased
concern
for
developmental
toxicity.
The
developmental
toxicity
LOAEL
is
125
mg/
kg/
day,
based
on
possible
skeletal
abnormalities
and
total
abnormalies.
The
developmental
toxicity
NOAEL
is
50
mg/
kg/
day.
The
developmental
toxicity
study
in
the
rat
is
classified
unacceptable/
upgradable,
pending
submission
of
acceptable
purity,
concentration,
stability
and
litter
data
and
historical
control
data.
A
letter
dated
9/
26/
01
from
the
registrant
provided
no
additional
information
about
this
rabbit
developmental
toxicity
study
other
than
the
doses
were
not
analyzed
and
that
a
repeat
rabbit
developmental
toxicity
was
currently
being
conducted.
4.4
Reproductive
Toxicity
Adequacy
of
data
base
for
Reproductive
Toxicity:
The
data
base
for
reproductive
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
There
was
no
evidence
of
qualitative
or
quantitative
susceptibility
in
a
two
generation
study
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
12
of
reproduction.
870.3800
Reproduction
and
Fertility
Effects
Rat
Executive
Summary:
In
a
two
generation
reproduction
study,
hexazinone
(98%
a.
i.,
Lot
No.
T02118994)
was
administered
to
groups
of
30
male
and
30
female
Sprague
Dawley
rats
in
the
diet
at
concentrations
of
0,
200,
2000,
or
5000
ppm
(MRID
42066501).
One
litter
was
produced
in
the
first
generation
and
two
litters
were
produced
in
the
second
generation.
Test
substance
intake
for
the
treated
F0
groups
was
11.8,
117,
and
294
mg/
kg/
day,
respectively,
for
males
and
14.3,
143,
and
383
mg/
kg/
day,
respectively,
for
females.
Test
substance
intake
for
the
treated
F1
groups
was
15.3,
154,
and
399
mg/
kg/
day,
respectively,
for
males
and
17.7,
180,
and
484
mg/
kg/
day,
respectively,
for
females.
F0
and
F1
parental
animals
were
administered
test
or
control
diet
for
73
or
105
days,
respectively,
prior
to
mating,
throughout
mating,
gestation,
and
lactation,
and
until
necropsy.
Deaths
of
several
F0
and
F1
parental
animals
were
considered
incidental
to
treatment.
No
treatment
related
clinical
signs
of
toxicity
were
observed
in
the
adult
animals
of
either
generation.
Gross
necropsy
was
unremarkable
and
no
microscopic
lesions
were
observed
in
selected
tissues
from
the
reproductive
tracts
of
male
and
female
parental
animals.
Body
weights
and
body
weight
gains
of
the
F0
males
were
not
affected
by
treatment.
Premating
body
weight
gains
by
the
mid
and
high
dose
F0
females
were
76%
and
62%
(p
#
0.05
for
both),
respectively,
of
the
control
level
resulting
in
final
premating
body
weights
93%
and
87%
(p
#
0.05),
respectively,
of
the
controls.
Body
weights
of
the
high
dose
F1
males
and
females
were
significantly
reduced
(p
#
0.05)
during
the
premating
interval
with
overall
weight
gains
87%
and
82%,
respectively,
of
the
control
group
amounts.
Reductions
in
body
weights
and
body
weight
gains
during
premating
for
the
mid
and
high
dose
F0
and
high
dose
F1
dams
continued
during
gestation
and
lactation.
Food
consumption
during
premating
was
similar
between
the
treated
and
control
groups
for
males
and
females
of
both
generations.
However,
during
gestation
significantly
(p
#
0.05)
lower
food
consumption
was
noted
for
the
high
dose
F1
dams
during
production
of
both
litters
and
for
the
middose
F1
dams
during
production
of
the
second
litter.
There
was
a
statistically
significant
increase
in
absolute
P0
testes
weight
that
appeared
to
be
dose
related,
but
a
nominally
decrease
absolute
F1
adult
testes
weight
in
the
5000
ppm
dose
groups.
The
F1
testes
weight
change
did
not
appear
to
dose
related.
The
testes
weight
changes
in
males
would
appear
to
be
incidental.
Therefore,
the
systemic
toxicity
LOAEL
is
2000
ppm
(117
154
mg/
kg/
day
for
males
and
143
180
mg/
kg/
day
for
females)
based
on
reduced
body
weight
and
body
weight
gains
by
F1
males
and
F0
and
F1
females.
The
systemic
toxicity
NOAEL
is
200
ppm
(11.8
15.3
mg/
kg/
day
for
males
and
14.3
17.7
mg/
kg/
day
for
females).
No
reproductive
effects
were
seen
in
the
study
except
for
the
weight
effects
on
offspring.
Live
birth
and
viability
indices
and
litter
survival
were
similar
between
the
treated
and
control
groups.
The
lactation
index
for
the
F2b
high
dose
litters
was
85.8%
(p
#
0.05)
compared
to
97.5%
for
the
control
group.
Pup
body
weights
were
decreased
throughout
lactation
in
the
mid
and
high
dose
groups
of
all
litters
as
compared
with
the
control
groups
with
statistical
significance
(p
#
0.05)
attained
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
13
at
most
time
points.
The
lower
pup
body
weights
were
more
pronounced
in
females
than
in
males.
F1
and
F2a
female
pup
weights
were
statistically
significantly
decreased
at
birth,
day
7
and
14
of
lactation
at
$2000
ppm.
There
were
no
obvious
reproductive
effects
other
than
the
pup
weight
decrement.
Therefore,
the
offspring
LOAEL
is
2000
ppm
(117
154
mg/
kg/
day
for
males
and
143
180
mg/
kg/
day
for
females)
based
on
reduced
female
pup
body
weights
at
birth
and
during
lactation.
The
reproductive
toxicity
NOAEL
was
200
ppm
(11.8
15.3
mg/
kg/
day
for
males
and
14.3
17.7
mg/
kg/
day
for
females).
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
guideline
requirements
for
a
reproductive
toxicity
study
[OPPTS
870.3800
(§
83
4)]
in
rats.
4.5
Chronic
Toxicity
Adequacy
of
data
base
for
chronic
toxicity:
The
data
base
for
chronic
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
The
chronic
study
in
dogs
showed
severe
body
weight
decrement,
changes
in
liver
related
clinical
chemistry
values,
and
microscopic
lesions.
Body
weight
decrement
was
seen
in
a
chronic
carcinogenicity
studies
in
rats
and
mice.
Liver
toxicity
was
seen
in
mice.
870.4100a
Chronic/
Carcinogenic
Toxicity
Rat
See
Section
below
on
Carcinogenicity
study
in
rats
(870.4300
Chronic/
Carcinogenicity
in
rats).
870.4100b
Chronic
Toxicity
Dog
EXECUTIVE
SUMMARY:
In
a
one
year
chronic
toxicity
study,
hexazinone
(98%
a.
i.,
Lot
No.
T02118994)
was
administered
to
groups
of
5
male
and
5
female
beagle
dogs
in
the
diet
at
concentrations
of
0,
200,
1500,
or
6000
ppm
(MRID
42162301).
Time
weighted
average
doses
for
the
treated
groups
were
5.00,
41.24,
and
161.48
mg/
kg/
day,
respectively,
for
males
and
4.97,
37.57,
and
166.99
mg/
kg/
day,
respectively,
for
females.
All
animals
survived
to
scheduled
necropsy.
Treatment
related
clinical
signs
of
toxicity
included
the
observation
of
thinness
in
1/
5
mid
dose
males,
3/
5
high
dose
males,
and
1/
5
high
dose
females.
Body
weights
of
the
high
dose
groups
were
significantly
(p
#
0.05)
less
than
those
of
the
control
throughout
most
of
the
study.
Final
body
weights
of
the
high
dose
males
and
females
were
78%
and
67%,
respectively,
of
the
control
levels.
Food
consumption
by
the
high
dose
groups
was
slightly
(n.
s.)
less
than
that
of
the
controls
throughout
the
study
with
statistical
significance
(p
#
0.05)
attained
for
females
at
week
52.
Overall
food
consumption
(weeks
1
52)
for
high
dose
males
and
females
was
85%
(n.
s.)
and
74%
(p
#
0.05),
respectively,
of
the
control
group
levels.
Body
weights
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
14
and
food
consumption
for
the
low
and
mid
dose
groups
were
not
affected
by
treatment.
No
treatment
related
ophthalmological
lesions,
changes
in
urinalysis
parameters,
or
gross
necropsy
findings
were
noted.
A
moderate
macrocytic
anemia
was
observed
in
the
high
dose
groups
as
evidenced
by
slight
or
significant
(p
#
0.05)
decreases
in
RBC
counts,
hemoglobin,
and
hematocrit
and
increases
in
MCV
and
MCH
in
one
or
both
sexes
throughout
the
study.
Cholesterol
levels
were
significantly
(p
#
0.05)
decreased
in
the
high
dose
groups
beginning
at
week
13
for
males
(52
64%
of
controls)
and
at
week
26
for
females
(45
51%
of
controls).
Albumin
levels
were
significantly
(p
#
0.05)
decreased
in
the
mid
dose
males
(93%
of
controls)
at
week
13
only,
and
in
the
high
dose
males
(74
78%
of
controls)
and
females
(75
82%
of
controls)
throughout
the
study.
Beginning
on
week
13
or
26,
the
high
dose
groups
had
aspartate
aminotransferase
levels
140
203%
(p
#
0.05)
of
the
control
values
and
alanine
aminotransferase
levels
206
276%
(p
#
0.05)
of
the
control
values.
Alkaline
phosphatase
levels
were
significantly
(p
#
0.05)
increased
in
the
mid
dose
males
(259
409%
of
controls)
and
females
(163
194%
of
controls;
n.
s.)
beginning
at
week
26
and
in
the
high
dose
males
(346
1363%
of
controls)
and
females
(307
559%
of
controls)
beginning
at
week
13.
For
the
high
dose
animals,
decreases
in
absolute
testes
weights
in
males
and
kidney,
heart,
and
brain
weights
in
females
(
12%)
and
increases
in
relative
liver
weights
in
males
and
females
were
considered
due
to
lower
final
body
weights
of
these
animals
as
compared
with
controls.
Microscopic
lesions
in
the
liver
of
high
dose
animals
included
concentric
membranous
bodies
in
4
males
and
5
females,
centrilobular
single
cell
necrosis
in
3
males
and
3
females,
hepatocellular
pigment
in
3
males
and
3
females,
and
vacuolation
in
3
males
and
4
females.
In
addition
vacuolation
was
observed
in
one
mid
dose
male
and
pigment
and
membranous
bodies
were
each
observed
in
one
mid
dose
female.
These
lesions
were
not
seen
in
control
or
low
dose
animals.
Therefore,
the
LOAEL
for
hexazinone
in
male
and
female
beagle
dogs
is
1500
ppm
(41.24
and
37.57
mg/
kg/
day,
respectively)
based
on
thinness
in
one
male
and
hepatotoxicity
as
evidenced
by
changes
in
clinical
chemistry
parameters
and
microscopic
lesions.
The
NOAEL
is
200
ppm
(5.00
and
4.97
mg/
kg/
day,
respectively).
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
guideline
requirements
for
a
chronic
toxicity
study
[OPPTS
870.4100
(§
83
1b)]
in
dogs.
4.6
Carcinogenicity
Adequacy
of
data
base
for
Carcinogenicity:
The
data
base
for
carcinogenicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
HED's
Carcinogenicity
Peer
Review
Committee
classified
hexazinone
as
a
Group
D
chemical
(not
classifiable
as
to
human
carcinogenicity)
(7/
27/
94).
This
classification
was
based
on
the
following
weight
of
evidence
considerations.
In
rats,
females
showed
no
evidence
for
carcinogenicity;
males
showed
a
significant
trend
only
for
thyroid
adenomas.
In
mice,
the
evidence
of
carcinogenicity
was
equivocal:
a
positive
trend
test
for
liver
tumors
was
observed
only
in
female
mice,
but
no
significant
difference
was
seen
by
pair
wise
comparison
(CPRC
Report
dated
July
27,
1994).
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
15
870.4200b
Carcinogenicity
(feeding)
Mouse
EXECUTIVE
SUMMARY:
In
this
mouse
oncogenicity
study
(MRIDs
00079203,
41359301,
42509301
and
43202901),
hexazinone
($95%
a.
i.;
Lot/
Batch
#:
H
11,
265
and
265
2)
was
administered
in
the
diet
to
CD
1
mice
(80/
sex/
group)
for
up
to
104
weeks
at
nominal
doses
of
0,
200,
2500
or
10,000
ppm
(equivalent
to
28,
366
and
1635
mg/
kg/
day
in
males
and
0,
34,
450
and
1915
mg/
kg/
day
in
females).
No
treatment
related
differences
were
observed
in
mortality,
food
consumption,
food
efficiency
or
hematology.
Hepatotoxicity
was
evident
at
the
terminal
sacrifice.
Macroscopic
liver
nodule/
mass
(%
treated
vs
%
controls;
n
=
28
55)
was
observed
in
males
at
2500
(39%
vs
7%)
and
10,000
ppm
(33%).
Increased
incidences
(%
treated
vs
0%
controls;
n
=
38
55)
in
the
following
microscopic
liver
lesions
were
observed:
hyperplastic
nodule(
s)
(includes
both
foci
of
cellular
alteration
and
adenoma)
in
males
at
2500
(39%
vs
20%)
and
10,000
ppm
(36%)
and
in
females
at
10,000
ppm
(15%
vs
3%);
and
necrosis
(severity
and
type
unspecified)
in
the
10,000
ppm
males
(36%
vs
7%).
Centrilobular
hepatocyte
hypertrophy
was
observed
(%
treated
vs
%
controls)
at
the
terminal
sacrifice
(n
=
38
55)
in
males
at
2500
(18%
vs
0%)
and
10,000
ppm
(98%)
and
in
females
at
10,000
ppm
(46%
vs
0%)
and
in
the
dead
and
moribund
males
(n
=
25
40)
at
2500
(44%
vs
0%)
and
10,000
ppm
(60%).
Increased
(p#0.05
or
0.01)
liver/
gall
bladder
weights
were
observed
at
10,000
ppm
in
males
in
both
absolute
and
relative
to
body
weights
and
in
females
in
relative
to
body
weight.
Other
signs
of
toxicity
were
evident.
Distal
tail
tip
sloughing
and/
or
discoloration
was
observed
at
10,000
ppm
in
males
at
Weeks
13
104
and
in
females
at
Weeks
5
and
13
104.
Macroscopically,
tip
of
tail
missing/
sloughed
was
observed
at
the
terminal
sacrifice
in
the
10,000
ppm
males
(31%
vs
5%)
and
females
(61%
vs
11%)
and
in
the
dead
and
moribund
10,000
ppm
females
(46%
vs
2%).
The
toxicological
significance
of
these
findings
was
unclear.
Minor
decreases
(p#0.05
or
0.01)
in
body
weights
were
observed
in
the
10,000
ppm
treatment
groups
at
Weeks
13
104
in
both
sexes.
Overall
body
weight
gains
(calculated
by
the
reviewers)
were
decreased
in
the
10,000
ppm
males
(925%)
and
females
(931%).
The
LOAEL
is
2500
ppm
for
males
(equivalent
to
366
mg/
kg/
day)
based
on
gross
liver
nodules/
masses,
hyperplastic
nodules
in
the
liver
and
centrilobular
hepatocyte
hypertrophy
and
10,000
ppm
for
females
(equivalent
to
1915
mg/
kg/
day
[limit
dose])
based
on
decreased
body
weights,
increased
relative
liver/
gall
bladder
weights,
hyperplastic
nodules
and
centrilobular
hepatocyte
hypertrophy.
The
NOAEL
is
200
ppm
(equivalent
to
28
mg/
kg/
day)
for
males
and
2500
ppm
(equivalent
to
450
mg/
kg/
day)
for
females.
Liver
samples
were
first
evaluated
using
the
term
hyperplastic
nodule
which
did
not
clearly
distinguish
neoplasia
from
non
neoplasia.
Re
evaluation
was
conducted
to
make
this
distinction,
and
no
significant
differences
were
observed
between
the
treatment
groups
and
the
concurrent
controls.
However
positive
trends
(p<
0.05)
were
observed
(%
treated
vs
%
controls)
in
focus/
foci
of
cellular
alteration
in
males,
hepatocellular
neoplasm(
s)
(including
adenoma,
sarcoma,
carcinoma,
leukemia,
and
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
16
lymphoma)
in
females,
and
singular
hepatocellular
adenoma
in
females.
Focus/
foci
of
cellular
alteration
were
observed
in
males
at
2500
(11.3%
vs
5.0%)
and
10,000
ppm
(24.1%)
and
females
at
10,000
ppm
(12.5%
vs
3.8%)
beginning
at
Week
57.
Singular
hepatocellular
adenoma
was
observed
in
the
10,000
ppm
females
(7.5%
vs
2.5%)
beginning
at
Week
77.
Hepatocellular
neoplasm(
s)
were
observed
in
the
10,000
ppm
females
(8.8%
vs
2.5%).
A
carcinoma
in
the
10,000
ppm
treatment
groups
was
first
observed
at
Week
65.
The
incidence
of
carcinomas
were
within
historical
control
ranges
for
each
sex,
while
the
incidence
of
adenomas
were
increased
by
3.21%
in
the
10,000
ppm
females.
A
dose
dependent
increase
in
adenomas
was
not
observed
in
males.
The
Health
Effects
Division
Carcinogenicity
Peer
Review
Committee
(CPRC)
concluded
that
hexazinone
should
be
classified
as
a
Group
D
(not
classifiable
as
to
human
carcinogenicity)(
7/
27/
94).
Under
the
conditions
of
this
study,
evidence
of
carcinogenic
potential
was
equivocal:
a
positive
trend
test
for
neoplasia
was
observed
in
female
mice,
but
no
significant
difference
was
determined
by
pair
wise
comparison.
The
submitted
study
is
classified
as
acceptable
for
guideline
870
4200
carcinogenicity
study
in
mice.
870.4300
Chronic/
Carcinogenicity
Study
rat
EXECUTIVE
SUMMARY:
In
this
combined
chronic/
oncogenicity
study
(MRID
00108638),
hexazinone
(94
96%
a.
i.;
Lot/
Batch
#:
6897
40
and
74.25)
was
administered
in
the
diet
to
ChR
CD
rats
(36/
sex/
group)
for
up
to
25
months
at
nominal
doses
of
0,
0,
200,
1000,
or
2500
ppm
(equivalent
to
0,
0,
10.2,
53.4,
and
138.3
mg/
kg/
day
in
males
and
0,
0,
12.5,
67.5,
and
178.6
mg/
kg/
day
in
females).
No
treatment
related
differences
were
observed
in
mortality,
clinical
signs,
food
consumption,
hematology,
clinical
chemistry,
organ
weights,
and
gross
or
microscopic
pathology.
No
adverse
effects
were
observed
in
the
200
ppm
animals.
There
were
several
signs
of
general
toxicity,
but
a
target
organ
could
not
be
clearly
identified
at
any
dose.
Terminal
body
weights
were
decreased
8%
in1000
ppm
and
20%,
p#0.05,
in
the
2500
ppm
females.
A
decrease
in
overall
body
weight
gain
(Days
0
728;
calculated
by
the
reviewers)
was
also
observed
in
the
1000
(
10%)
and
2500
ppm
(
25%)
females.
Nominal
decreases
in
body
weight
and
body
weight
gain
(
3
to
5%)
occurred
in
males
at
1000
ppm
during
the
study,
which
may
have
been
biologically
significant
at
the
end
of
the
study
(
12%
body
weight
and
14%
for
body
weight
gain).
Decreases
(p
values
not
calculated)
in
total
food
efficiency
were
observed
in
females
at
1000
(
10%)
and
2500
ppm
(
25%)
and
in
males
at
1000
ppm
during
the
study
with
overall
decrement
in
food
efficiency
in
1000
ppm
males
(
10%).
In
males
at
2500
ppm,
food
efficiency
was
depressed
for
the
first
6
months
of
the
study
(
25%),
but
from
6
months
to
the
end
of
the
study,
it
was
increased
139%.
The
reviewer
noted
problems
interpreting
the
body
weights
and
food
efficiency
in
males
at
the
top
dose
level,
which
were
not
consistent
with
the
mid
dose
level.
For
the
first
6
months
of
the
study
in
males,
a
body
weight
decrement
due
to
probable
toxicity
was
seen
at
1000
and
2500
ppm.
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
17
After
6
months
food
efficiency
in
males
at
the
1000
ppm
remained
less
than
controls
(
56%)
while
food
efficiency
at
2500
ppm
in
males
was
higher
than
controls
(+
139%)(
Table
4).
By
the
end
of
the
study,
male
body
weight
at
1000
ppm
was
12%
and
body
weight
gain
14%,
where
as
body
weight
and
body
weight
gain
in
males
at
2500
ppm
was
+3%
for
both
weight
and
gain.
The
reason
for
this
recovery
in
male
body
weight
decrement
at
2500
ppm
is
unknown,
but
it
appears
to
be
real.
[Since
absolute
and
relative
liver
weights
were
decreased
in
males
at
2500
ppm,
liver
enzyme
induction
allowing
the
recovery
seems
unproven.]
The
body
weight
decrement
at
1000
and
2500
ppm
with
recovery
in
body
weight
at
2500
ppm
indicates
the
an
adequate
dose
level
to
test
for
carcinogenicity
in
males
was
approached,
but
probably
not
attained.
Other
treatment
groups
were
similar
to
the
average
of
concurrent
controls.
Dosing
was
considered
adequate
based
on
decreased
body
weights,
body
weight
gains,
and
food
efficiency
in
the
2500
and
1000
ppm
females
and
food
efficiency
and
body
weights
in
the
2500
ppm
males
for
the
first
6
months.
Body
weight
(
12%)
and
body
weight
gain
14
in
males
at
1000
ppm
were
decreased
at
the
end
of
the
study,
in
addition
overall
food
efficiency
(
14%)
was
decreased
by
the
end
of
the
study.
Thus
female
body
weight
and
body
weight
gain
was
decreased
sufficiently
to
adequately
test
for
carcinogenicity.
Male
body
weight
and
body
weight
gain
at
1000
ppm
appeared
to
be
adequate
to
test
for
carcinogenicity
by
the
end
of
the
study,
but
the
lack
of
dose
response
in
male
body
weight
and
body
weight
gain
at
2500
ppm
(showing
recovery
after
6
months
such
that
body
weight
and
body
weight
gain
were
higher
than
control
values)
may
indicate
problems
with
the
interpretation
of
the
body
weights
and
body
weight
gains
at
1000
ppm.
In
the
2500
ppm
males,
creatinine
was
increased
(NS)
in
the
urine
at
months
18
and
24
and
bilirubin
was
detected
at
month
18
and
24.
The
Sponsor
reported
that
the
urine
was
more
alkaline
in
the
2500
ppm
treatment
groups
(data
not
reported).
Also
at
2500
ppm,
decreased
(p#0.05)
absolute
and
relative
liver
and
kidney
organ
weights
were
observed
in
the
males
and
increased
(p#0.05)
relative
(to
body)
stomach
and
kidney
organ
weights
were
observed
in
the
females.
However,
histopathological
data
did
not
corroborate
these
findings.
The
LOAEL
is
1000
ppm
for
males
and
females
(equivalent
to
53.3
for
males
and
67.5
mg/
kg/
day
for
females)
based
on
decreased
body
weight
and
food
efficiency
in
males
and
females.
In
males
at
2500
ppm
the
body
weight
decrement
and
food
efficiency
decrement
occurred
only
for
the
first
6
months
of
the
study.
The
NOAEL
is
200
ppm
for
males
and
females
(10.2
for
males
and
12.5
mg/
kg/
day
for
females).
Neoplasm
data
were
evaluated
by
two
pathologists.
An
increase
incidence
of
thyroid
Ccell
adenomas
was
observed
in
the
2500
ppm
males,
but
when
analyzed
by
the
Fisher's
exact
test
(p>
0.10)
or
life
table
methods
(p>
0.20)
no
significant
differences
were
observed
between
controls
and
treated
groups.
Using
life
table
analyses
a
significant
(p<
0.05)
dose
response
trend
was
observed
in
thyroid
C
cell
tumors
in
only
one
of
the
two
pathology
reports.
Female
rats
did
not
show
any
potential
for
C
cell
thyroid
adenomas.
The
incidence,
malignancy
and
latency
of
tumors
were
comparable
among
control
and
treated
rats
of
both
sexes.
Under
the
conditions
of
this
study,
carcinogenic
potential
of
hexazinone
is
considered
negative.
The
submitted
study
is
classified
as
acceptable
for
guideline
870.4300
combined
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
18
chronic/
carcinogenicity
study
in
rats.
4.7
Mutagenicity
Adequacy
of
data
base
for
Mutagenicity:
The
data
base
for
Mutagenicity
is
considered
adequate
based
on
pre
1991
mutagenicity
guidelines.
Hexazinone
was
found
to
be
positive
for
mutagenicity
in
one
chromosomal
aberration
assay
(in
vitro
cytogenics)
(MRID#
00130709),
but
negative
in
the
remaining
studies.
It
is
concluded
that
the
test
material
was
clastogenic
in
both
of
the
non
activated
trials
and
was
also
clastogenic
in
the
one
adequate
S9
activated
trials.
Under
both
test
conditions,
concentrations
providing
evidence
of
clastogenicity
induced
an
acceptable
level
of
cytotoxicity
(>
50%
relative
cell
survival).
Thus,
the
findings
can
not
be
considered
to
be
a
secondary
effect
of
cytotoxicity.
Nevertheless,
the
outcome
of
the
induced
structural
damage
(i.
e.,
primarily
chromatid
and
chromosome
breaks)
is
unclear
since
these
types
of
structural
aberrations
would
not
likely
be
passed
on
to
daughter
cells.
Because
unambiguous
positive
results
were
achieved,
it
was
concluded
that
the
study
provided
adequate
evidence
that
INA3674
112
(hexazinone,
technical)
is
clastogenic
in
an
acceptable
study.
Gene
Mutation
4.7.1
Guideline
870.5100,
Reverse
mutation
in
Salmonella
EXECUTIVE
SUMMARY:
In
a
reverse
gene
mutation
assay
in
bacteria
(MRID
40826201),
strains
TA98,
TA100,
TA1535,
TA1537
and
TA1538
of
S.
typhimurium
were
exposed
to
S
triazine2,4
1H,
3H)
dione,
3
cyclohexyl
6
dimethylamino
1
methyl
(95%
a.
i.)
in
ethanol
at
concentrations
of
200,
400,
600,
800
and
1000
:g/
plate
without
mammalian
metabolic
activation
(S9
mix)
and
at
concentrations
of
400,
800,
1200,
1600
and
2000
:g/
mL
with
S9
mix.
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
male
Crl:
CD(
SD)
BR
rat
liver.
The
maximum
concentrations
of
S
triazine
2,4(
1H,
3H)
dione,
3
cyclohexyl
6
dimethylamino
1
methyl
tested
produced
little
or
no
cytotoxicity,
were
not
limited
by
solubility
and
were
not
a
limit
dose
for
the
assay.
No
statistically
significant
increases
in
the
number
of
revertants
per
plate
or
positive
linear
dose
response
were
seen.
The
solvent
and
positive
controls
induced
acceptable
responses
in
the
corresponding
strains.
There
was
no
evidence
of
induced
mutant
colonies
over
background.
This
study
is
classified
as
Unacceptable.
It
does
not
satisfy
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5100
(§
84
2)]
for
in
vitro
mutagenicity
[bacterial
reverse
gene
mutation]
data
and
should
have
used
higher
doses.
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
19
4.7.2
Guideline
870.5300,
Gene
mutation
at
HGPRT
locus
EXECUTIVE
SUMMARY:
In
a
mammalian
cell
gene
mutation
assay
at
the
HGPRT
locus
(MRID
No.
00076956),
Chinese
hamster
CHO
K1
BH4
cells
cultured
in
vitro
were
exposed
to
INA
3674
112,
(Lot
No.
7612
5E6E,
95%
a.
i.)
in
ethanol
in
two
trials.
Concentrations
used
in
Trial
1
were
2.0,
11.1,
13.1,
13.9
and
14.3
mM
under
nonactivated
conditions
and
concentrations
of
2.0,
7.9,
8.9,
9.3
and
9.9
mM
under
activated
conditions
(S9
mix).
Concentrations
used
in
Trial
2
were
2.0,
5.9,
11.1,
13.1
and
13.9
mM
without
S9
mix
and
concentrations
of
2.0,
7.9,
8.9,
9.3
and
9.9
mM
with
S9
mix.
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
male
Charles
River
CD®
rat
livers.
INA
3674
112
was
tested
up
to
cytotoxic
concentrations.
In
Trial
1,
the
cultures
treated
at
14.3
mM
were
not
plated
for
mutation
determination
due
to
cytotoxicity
and
in
both
Trials
1
and
2,
those
cultures
treated
at
13.9
mM
were
excluded
from
analysis
because
no
mutants
were
seen.
No
statistically
significant
increases
in
mutant
frequency
over
solvent
control
values
were
seen
with
or
without
S9
mix
in
either
Trial
1
or
2.
The
expected
marked
increase
in
the
mutation
were
seen
with
the
positive
controls.
There
was,
however,
no
indication
that
INA
3674
112
induced
a
mutagenic
effect
either
in
the
presence
or
the
absence
of
S9
activation.
This
study
is
classified
as
acceptable.
It
satisfies
the
requirement
for
FIFRA
Test
Guideline
OPPTS
[870.5300
(§
84
2)]
for
in
vitro
mutagenicity
(mammalian
forward
gene
mutation)
data.
4.7.3
Guideline:
870.5375:
In
vitro
mammalian
cytogenics
(chromosomal
aberrations)
in
Chinese
hamster
CHO
cells.
EXECUTIVE
SUMMARY:
In
a
mammalian
cell
cytogenetics
assay
(MRID
No.
00130709),
Chinese
hamster
ovary
CHO
K1
BH4
cell
cultures
were
exposed
to
INA
3674
112
(Hexazinone,
95%
a.
i.)
in
ethanol
in
two
separate
trials.
Exposure
was
for
two
hours
with
activation
and
for
10
hours
without
activation.
Cells
were
harvested
10
hours
after
the
start
of
treatment.
In
Trial
1,
cells
were
treated
at
concentrations
of
1.58,
3.94,
15.85
and
19.82
mM
without
metabolic
activation
(S9
mix)
and
at
concentrations
of
0.32,
3.17,
7.93
and
15.85
mM
with
S9
mix.
In
Trial
2,
cells
were
treated
at
concentrations
of
1.58,
3.94,
7.93
and
15.85
without
S9
mix
and
at
concentrations
of
0.32,
3.17,
7.93
and
15.85
mM
with
S9
mix.
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
CD
rat
livers.
INA
3674
112
was
tested
up
to
cytotoxic
concentrations.
Based
on
the
results
of
a
preliminary
cytotoxicity
test,
upper
concentrations
of
23.78
mM
without
S9
mix
and
47.56
mM
with
S9
mix
were
selected
for
the
first
cytogenetic
assay
but
these
concentrations
proved
excessively
cytotoxic
and
were
not
scored
for
chromosomal
aberrations.
Without
S9
activation,
statistically
significant
increases
(p<
0.01)
in
structural
aberrations
per
cell
(excluding
gaps),
lesions
per
cell
and
percent
abnormal
cells
were
seen
at
15.85
mM
(Trials
1
and
2)
and
19.82
mM
(tested
in
Trial
1
only).
Relative
percent
survival
(RPS)
at
this
level
was
.50%.
The
percent
abnormal
cells
averaged
over
all
cultures
from
both
trials
was
28.0%
and
21.5%
at
19.82
and
15.85
mM,
respectively,
compared
to
the
solvent
control
values
of
2.0%
(0.5%
ethanol
in
Trial
2)
and
7.0%
(0.75%
ethanol
in
Trial
1).
The
percent
abnormal
cells
in
positive
control
cultures
was
18%
in
both
Trial
1
(4.83
mM
EMS)
and
Trial
2
(6.44
mM
EMS).
In
the
presence
of
S9
mix,
no
statistically
significant
increases
in
chromosomal
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
20
aberration
induction
were
seen
in
Trial
1;
however,
very
low
positive
control
values
indicated
a
problem
with
the
S9
mix.
Statistically
significant
increases
were
seen
at
15.85
mM
in
Trial
2;
RPS
at
15.85
mM
was
75%.
There
was
a
statistically
significant
dose
related
trend
for
all
three
parameters.
The
statistically
significant
(p
<0.01)
increases
at
15.85
mM
remained
when
the
data
from
Trial
1
and
2
were
combined
(average
of
20%
abnormal
cells
compared
to
10%
for
the
solvent
control).
The
predominant
aberrations
with
or
without
S9
mix
were
chromatid
and
isochromatid
breaks.
Solvent
and
positive
controls
(except
the
positive
control
in
Trial
1
with
S9
mix)
induced
the
appropriate
responses.
INA
3674
112
was
positive
for
the
induction
of
structural
chromosomal
aberrations
in
both
the
presence
and
absence
of
S9
mix.
This
study
is
classified
as
Acceptable/
guideline
and
satisfies
the
requirement
for
FIFRA
Test
4.7.4
Guideline
870.5385:
In
vivo
cytogenics
assay
in
rat
bone
marrow
cells
EXECUTIVE
SUMMARY:
In
a
mammalian
cell
cytogenetics
assay
(MRID
00131355),
in
bone
marrow
cells
of
Sprague
Dawley
CD
rats,
three
rats/
dose/
sex/
harvest
time
were
exposed
to
H#
14,555
in
corn
oil
(
assumed
100%
a.
i.)
at
doses
of
100,
300
and
1000
mg/
kg
by
oral
gavage.
Bone
marrow
cells
were
harvested
at
6,
12,
24
and
48
hours
post
treatment.
The
highest
dose
tested
(1000
mg/
kg)
was
lethal.
A
major
limitation
of
this
study
was
the
number
of
animals
treated
and
the
number
of
cells
analyzed
per
animal.
At
most,
three
rats/
sex/
dose/
harvest
time
were
treated
with,
at
most,
50
cells
per
rat
analyzed.
Few
or
no
analyzable
cell
were
available
from
many
rats.
Positive
control
values
were
significantly
(p=
0.03)
increased.
There
was
no
evidence
that
H#
14,
14,555
induced
an
increase
in
the
incidence
of
chromosomal
aberrations
in
the
bone
marrow
cells
of
treated
animals.
This
study
is
classified
as
Unacceptable.
The
number
of
cells
analyzed
and
the
number
of
rats
treated
was
insufficient.
The
study
does
not
satisfy
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5385
(§
84
2)]
for
in
vivo
cytogenetic
mutagenicity
data.
4.7.5
Guideline
870.5395:
Micronucleus
assay
in
mouse
bone
marrow
EXECUTIVE
SUMMARY:
In
a
Crl:
CD
1
(ICR)
BR
mouse
bone
marrow
micronucleus
assay
(MRID
45124401),
5
mice/
sex/
dose/
harvest
time
were
treated
orally
with
Hexazinone
25L
(Lot
No.
9912033,
25%
Hexazinone
a.
i.
(24.5%
by
analysis)
and
75%
inert
ingredients)
at
doses
of
1000,
2000
and
3000
mg/
kg.
Bone
marrow
cells
were
harvested
at
24
and
48
hours
post
treatment
and
examined
for
micronucleated
polychromatic
erythrocytes
(MPCEs).
The
vehicle
was
Milli
Q
®
water.
Signs
of
toxicity
noted
at
3000
mg/
kg
included:
death,
convulsions,
half
shut
eyes,
head
tilt,
irregular
respiration,
lethargy,
low
carriage,
pallor,
prostration,
uncontrollable
spinning,
shovel
nosing,
straining
up
on
toes
and
tremors.
Micronuclei
were
scored
in
bone
marrow
from
mice
treated
at
3000
mg/
kg
and
from
the
solvent
and
positive
controls.
Mice
from
the
two
lower
dose
groups
were
not
evaluated
for
micronuclei
induction.
No
statistically
significant
increases
in
the
frequency
of
MPCEs
or
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
21
in
the
PCE/
NCE
ratio
over
the
solvent
control
values
were
seen
in
either
sex
at
either
the
24
or
48
hour
harvest
time.
The
solvent
and
positive
control
values
were
appropriate
and
within
the
testing
laboratory's
historical
control
ranges.
There
was
no
evidence
that
Hexazinone
25L
induced
a
clastogenic
or
aneugenic
effect
in
bone
marrow
at
any
harvest
time.
This
study
is
classified
as
Acceptable/
Guideline.
It
satisfy
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5395
(§
84
2)]
for
in
vivo
cytogenetic
mutagenicity
data.
4.7.6
Guideline
8760.5550:
Unscheduled
DNA
synthesis
assay
in
rat
hepatocytes
EXECUTIVE
SUMMARY:
In
an
unscheduled
DNA
synthesis
assay
(MRID
00130708),
primary
rat
hepatocyte
cultures
were
exposed
to
INA
3674
112
(Lot
No.
7612
5E6E,
95%
a.
i.)
in
ethanol
for
18
hours
at
concentrations
of
1
x
10
5
,
1
x
10
4
,
1
x
10
3
,
1
x
10
2
,
0.1,
1.0,
10.0
and
30.0
mM
in
Trial
1
and
at
concentrations
of
1
x
10
5
,
1
x
10
4
,
1
x
10
3
,
1
x
10
2
,
0.1,
1.0,
5.0,
10.0
and
30.0
mM
in
Trial
2.
INA
3674
112
was
tested
up
to
the
highest
achievable
concentration
in
the
solvent.
Two
slides
per
dose,
25
cells
per
slide
were
evaluated
for
UDS
induction
in
Trial
1.
One
slide
per
dose,
25
cells
per
slide
were
evaluated
in
Trial
2.
The
author
did
not
report
that
the
slides
were
coded
prior
to
analysis.
The
average
net
nuclear
grain
counts
of
test
material
treated
cells
in
Trial
1
were
all
less
than
zero
with
the
exception
of
one
slide
at
1
x
10
5
mM
(0.1
±
9.6)
and
one
slide
at
1.0
mM
(1.6
±
5.2).
The
average
net
nuclear
grain
count
was
below
zero
for
all
test
material
concentrations
in
Trial
2
with
the
exception
of
0.1
mM
where
the
average
net
nuclear
grain
count
was
0.0
±
2.9.
The
criterion
for
a
positive
response
was
an
average
net
nuclear
grain
count
of
at
least
five
in
two
experiments
at
any
tested
concentration.
The
results
were
thus
negative.
The
number
of
cells
in
repair
was
not
reported.
The
solvent
and
positive
(DMBA)
controls
induced
the
appropriate
responses.
There
was
no
evidence
that
unscheduled
DNA
synthesis,
as
determined
by
radioactive
tracer
procedures
[nuclear
silver
grain
counts]
was
induced.
This
study
is
classified
as
Acceptable/
Guideline.
It
satisfies
the
requirement
for
FIFRA
Test
Guideline;
OPPTS
870.5550
[§
84
2]
for
other
genotoxic
mutagenicity
data.
Compliance
statements
were
not
provided.
4.8
Neurotoxicity
Adequacy
of
data
base
for
Neurotoxicity:
No
neurotoxicity
data
are
required.
870.6100
Delayed
Neurotoxicity
Study
Hen
Study
is
not
required
of
hexazinone,
which
is
not
an
organophosphate.
870.6200
Acute
Neurotoxicity
Screening
Battery
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
22
Study
not
required
870.6200
Subchronic
Neurotoxicity
Screening
Battery
Study
not
required.
870.6300
Developmental
Neurotoxicity
Study
Study
not
required.
4.9
Metabolism
Adequacy
of
data
base
for
metabolism:
The
data
base
for
metabolism
is
considered
to
be
complete.
No
additional
studies
are
required
at
this
time.
870.7485
Metabolism
Rat
EXECUTIVE
SUMMARY:
A
metabolism
study
(MRID
00109237
&
00140162)
was
conducted
to
evaluate
the
absorption,
distribution,
metabolism,
and
excretion
of
hexazinone
in
male
and
female
CD
rats.
Radiolabeled
(
14
C
at
position
2
or
4
on
the
cyclohexyl
ring)
hexazinone,
(Lot
#
not
reported,
purity
>95%,
radiochemical
purity
>99%)
was
administered
by
gavage
to
groups
of
one
male
and
one
female
rat
at
concentrations
of
14
mg/
kg
or
1000
mg/
kg.
A
third
group
of
two
male
and
two
female
rats
received
unlabeled
hexazinone
(~
5
mg/
kg/
day)
in
the
diet
for
three
weeks
before
being
given
a
single
14
mg/
kg
radiolabeled
gavage
dose.
Mass
balance
was
excellent
and
ranged
from
95
102%
recovery
for
all
treatment
groups.
Based
on
the
amount
of
radiolabel
recovered
in
the
urine
and
cage
wash,
absorption
of
the
test
material
was
at
least
83%
with
no
dose
or
sex
dependent
differences
noted.
By
72
hours
after
treatment,
essentially
none
of
the
radiolabeled
test
material
was
present
in
the
tissues.
Urine
was
the
primary
route
of
elimination
accounting
for
~83%
of
the
administered
dose.
Urinary
elimination
was
rapid
and
~96%
complete
within
48
hours
of
treatment.
No
apparent
sex
or
dose
related
differences
were
found.
Fecal
excretion
was
a
minor
route
of
elimination,
accounting
for
~16%
of
the
dose
and
was
rapid
with
~95%
occurring
within
72
hours
of
treatment.
Once
again,
no
apparent
sex
or
dose
related
differences
were
found.
Essentially
none
of
the
parent
compound
was
found
in
the
urine
(-83%
of
dose)
or
feces
(-16%
of
dose)
of
male
and
female
rats
following
multiple
low
dose
or
a
single
high
dose
treatment
with
hexazinone.
(Molecular
structures
of
the
parent
and
metabolites
can
be
found
in
Section
IV,
Appendix.)
3(
4
hydroxycyclohexyl)
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
(metabolite
A)
and
3(
4
hydroxycyclohexyl)
6(
methylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
(metabolite
C)
comprised
~66
and
28%,
respectively,
of
the
identified
fecal
metabolites
in
males
and
females.
These
two
metabolites
resulted
from
hydroxylation
of
the
cyclohexyl
ring
and
differed
only
by
the
metabolic
conversion
of
the
6
dimethyl
amine
to
a
secondary
methyl
amine.
No
sex,
or
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
23
dose
related
differences
in
the
formation
and
excretion
of
these
metabolites
were
found.
Three
metabolites
were
identified
in
the
urine
of
males
and
females
(metabolite
A
and
C,
-57%
and
-28%
of
identified
metabolites,
respectively)
.
Two
of
the
metabolites
were
identical
to
those
found
in
the
feces
.
The
third
metabolite
(3(
cyclohexyl)
6(
methylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione)
(metabolite
B,
-9%
of
urinary
metabolites)
resulted
from
demethylation
of
the
6
dimethyl
amine
group
to
form
a
secondary
amine
without
hydroxylation
of
the
4
position
on
the
cyclohexyl
ring.
Approximately
3%
of
the
urine
metabolites
were
unidentified
polar
compounds
and
5%
were
isolated
from
the
hydrolyzed
urine,
suggesting
they
had
undergone
glucuronide
or
sulfate
conjugation.
No
differences
between
the
sexes
or
dose
groups
in
the
metabolic
conversion
of
hexazinone
were
found.
This
metabolism
and
disposition
study
with
rats
is
considered
Acceptable/
Nonguideline
and
does
satisfy
the
requirements
for
a
Metabolism
and
Pharmacokinetics
Study
[OPPTS
870.7485
(§
85
1)].
Major
deficiencies
include
the
use
of
1
2
male
and
female
rats/
group;
no
submission
of
test
material
lot
numbers,
stability,
or
dose
confirmation
data;
and
study
dates.
4.10
Special/
Other
Studies
None
available.
5.0
TOXICITY
ENDPOINT
SELECTION
5.1
See
Section
9.2
for
Endpoint
Selection
Table.
5.2
Dermal
Absorption
No
dermal
absorption
study
is
available.
For
dermal
absorption,
the
NOAEL
from
the
21
day
dermal
toxicity
study
at
the
limit
dose
of
1000
mg/
kg/
day
was
considered
a
lower
bound
for
the
LOAEL,
which
was
compared
with
LOAEL
of
250
mg/
kg/
day
from
the
range
finding
rabbit
study
(MRID#
00028863).
The
ratio
of
these
two
numbers
was
used
to
estimate
a
dermal
absorption
factor
of
25%.
The
range
finding
study
was
chosen
instead
of
the
main
rabbit
developmental
toxicity
study
(MRID#
00028863)
for
comparison
because
the
main
study
was
considered
to
be
unacceptable
for
regulatory
purposes.
Dermal
Absorption
Factor:
25
%
5.3
Classification
of
Carcinogenic
Potential
5.3.1
Conclusions
There
was
no
evidence
of
treatment
related
tumors
in
chronic
rat
or
mouse
studies.
5.3.2
Classification
of
Carcinogenic
Potential
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
24
The
RfD/
Peer
Review
Committee
has
classified
hexazinone
as
a
group
D
chemical;
no
evidence
of
carcinogenicity
in
rats
and
in
mice
insufficient
evidence
of
human
carcinogenic
potential.
5.3.3
Quantification
of
Carcinogenic
Potential
Not
required.
6.0
FQPA
CONSIDERATIONS
6.1
Special
Sensitivity
to
Infants
and
Children
There
was
no
evidence
of
quantitative
or
qualitative
postnatal
susceptibility
in
a
twogeneration
study
of
reproduction.
There
was
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
following
in
utero
exposure
to
rats
or
rabbits
in
developmental
toxicity
studies.
However,
the
rabbit
developmental
toxicity
study
was
unacceptable/
upgradable.
Until
another
study
is
review,
a
10X
uncertainty
factor
for
the
data
gap
will
remain.
In
rats,
no
developmental
toxicity
was
seen
at
the
highest
dose
level
tested,
and
in
rabbits,
developmental
effects
were
seen
at
a
dose
that
was
higher
than
that
showing
maternal
toxicity.
6.2
Recommendation
for
a
Developmental
Neurotoxicity
Study
No
neurotoxic
potential
was
seen
in
any
of
the
studies.
A
developmental
neurotoxicity
study
is
not
required.
7.0
OTHER
ISSUES
None
8.0
REFERENCES:
MRID
00028863.
Unknown
(1980)
Teratology
Study
in
Rabbits.
E.
I.
du
Pont
de
Nemours
and
Company,
Inc.,
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
Newark,
DE.
Laboratory
Project
Id.:
Haskell
Laboratory
Report
No.
201
522,
February
14,
1980.
Unpublished.
MRID
00076956.
McCooey,
K.
T.,
and
Krahn,
D.
F.
(1980).
Chinese
Hamster
Ovary
Cell
Assay
for
Mutagenicity.
E.
I.
du
Pont
de
Nemours
and
Company,
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
Elkton
Road,
Newark,
DE
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
25
19711.
Haskell
Laboratory
Report
No.:
56
81,
MR
No.:
0581
865,
December
1,
1980.
Unpublished.
MRID
00079203.
Unknown
(1981)
Two
Year
Feeding
Study
in
Mice.
International
Research
and
Development
Corporation,
Mattawan,
MI.
Laboratory
Project
Id.:
HLO414
81,
June
23,
1981.
Unpublished.
MRID
00104977.
Sherman,
H.
et.
al.
(1973)
Ninety
Day
feeding
Study
in
Rats
with
INA
3674.
Haskell
Laboratory.
Laboratory
Study
Id.:
235
73,
May
21,
1973.
Unpublished.
MRID
00108638.
Kaplan,
A.
M.,
Frazier,
C.
V.,
et
al.
(1977)
Long
Term
Feeding
Study
in
Rats
with
INA
3674.
E.
I.
du
Pont
de
Nemours
and
Company,
Inc.,
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
Newark,
DE.
Laboratory
Project
Id.:
Haskell
Laboratory
Report
No.
353
77,
May
13,
1977.
Unpublished
MRID
00109237.
Repisarda,
C.
(1982).
Metabolism
of
14
C
labeled
hexazinone
in
the
rat.
E.
I.
duPont
de
Nemours
and
Co.,
Biochemicals
Dept.,
Research
Div.,
Experimental
Station,
Wilmington,
DE
19898.
Document
No.
AMR
79
82.
Unpublished.
MRID
00114484.
Sherman,
H.
et
al.
(1973)
Three
Month
Feeding
Study
in
Dogs
with
INA3674
E.
I.
du
Pont
de
Nemours
and
Company,
Inc.,
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
Newark,
DE.
Laboratory
Project
Id.:
Haskell
Laboratory
Report
No.
408
73,
September
12,
1973.
Unpublished.
MRID
00114486.
Culik,
R.,
et
al.
(1974)
Teratogenic
Study
in
Rats
with
INA
3674.
E.
I.
du
Pont
de
Nemours
and
Company,
Inc.,
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
Newark,
DE.
Laboratory
Project
Id.:
Haskell
Laboratory
Report
No.
265
74,
April
9,
1974.
Unpublished.
MRID
00130708.
Summers,
J.
C.
(1983)
Unscheduled
DNA
Synthesis/
Rat
Hepatocytes
In
Vitro.
E.
I.
du
Pont
de
Nemours
and
Co.,
Inc.,
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
Elkton
Road,
P.
O.
Box
50,
Newark,
Delaware
19711.
Laboratory
Report
No.:
766
82,
MR
No.:
4508
001,
Date
Issued:
January
4,
1983.
Unpublished.
MRID
00130709.
Valachos,
D.,
Irr,
J.
and
Krahn,
D.
F.(
1982)
In
Vitro
Assay
for
Chromosome
Aberrations
in
Chinese
Hamster
Ovary
(CHO)
Cells.
E.
I.
du
Pont
Nemours
and
Co.,
Inc.,
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
26
Elkton
Road,
P.
O.
Box
50,
Newark,
Delaware
19711.
Laboratory
Report
No.
768
82,
MR
No.
4508
001,
December
3,
1982.
Unpublished.
MRID
00131355.
Farrow,
M.
G.,
Cortina,
T.
and
Zito,
M.
(1982).
In
Vivo
Bone
Marrow
Cytogenetic
Assay
in
Rats
with
H#
14,555:
Final
Report.
Hazleton
Laboratories
America,
Inc.,
9200
Leesburg
Turnpike,
Vienna,
Virginia
22180.
HLA
Project
number:
201
573,
December
9,
1982.
Unpublished.
MRID
00140162.
Rhodes,
R.
C.,
Jewell,
R.
A.,
Sherman,
H.
(No
date).
Metabolism
of
"Velpar"
weed
killer
in
the
rat.
E.
I.
duPont
de
Nemours
and
Co.,
Biochemicals
Dept.,
Experimental
Station
and
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
Wilmington,
DE
19898.
No
document
or
report
number.
Results
published
in
J.
Agric.
and
Food
Chem.,
28,
303
(1980)
MRID
40397501.
Mullin,
L.
S.
(1987)
Teratogenicity
Study
of
INA
3674
in
Rats.
E.
I.
du
Pont
de
Nemours
and
Company,
Inc.,
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
Newark,
DE.
Laboratory
Project
Id.:
Haskell
Laboratory
Report
No.
748
86,
January
30,
1987.
Unpublished.
MRID
40826201.
J.
F.
Russell
Jr.
and
D.
F.
Krahn
(1977).
Mutagenicity
Evaluation
of
Striazine
2,4(
1H,
3H)
dione,
3
cyclohexyl
6
dimethylamino
1
methyl
in
Salmonella
typhimurium.
E.
I.
du
Pont
de
Nemours
and
Company,
Inc.,
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
Elkton
Road,
P.
O.
Box
50,
Newark,
Delaware
19714.
Haskell
Laboratory
Report
No.
588
77,
MR
No.
0581
693;
Date
Issued:
July
29,
1977.
Unpublished.
MRID
41309005.
Malek,
D.
(1989).
Repeated
Dose
Dermal
Toxicity:
21
Day
Study
with
DPXA3674
207
(Hexazinone)
in
Rabbits.
E.
I.
du
Pont
de
Nemours
and
Company,
Inc.,
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
P.
O.
Box
50,
Elkton
Road,
Newark,
DE
19714.
Study
No.
HLA
673
89.
November
22,
1989.
Unpublished.
MRID
41359301.
Goldenthal,
E.
I.
(1989)
Supplement
1
to:
Two
Year
Feeding
Study
in
Mice
with
Hexazinone.
International
Research
and
Development
Corporation,
Mattawan,
MI.
Laboratory
Project
Id.:
HLO
414
81,
November
22,
1989.
Unpublished.
MRID
42066501.
Mebus,
C.
A.
(1991).
Reproductive
and
fertility
effects
with
IN
A3674
207;
multigeneration
reproduction
study
in
rats.
Haskell
Laboratory,
Newark,
Delaware.
Study
No.
HLA
404
91.
September
11,
1991.
Unpublished.
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
27
MRID
42162301.
Dalgard,
D.
W.
(1991)
Chronic
toxicology
study
in
dogs
with
DPX
A3674
207
(Hexazinone).
Hazleton
Washington,
Inc.,
9200
Leesburg
Turnpike,
Vienna,
VA
22182.
Laboratory
Study
No.
201
905.
November
5,
1991.
Unpublished.
MRID
42509301.
Slone,
Jr.,
T.
W.
(1992)
Supplement
1
to:
Two
Year
Feeding
Study
in
Mice
with
Hexazinone.
E.
I.
du
Pont
de
Nemours
and
Company,
Newark,
DE.
Laboratory
Project
Id.:
HLO
414
81,
October
2,
1992.
Unpublished.
MRID
43202901.
Slone,
Jr.,
T.
W.,
(1994)
Supplement
No.
3:
Two
Year
Feeding
Study
in
Mice
with
Hexazinone.
E.
I.
du
Pont
de
Nemours
and
Company,
Newark,
DE.
Laboratory
Project
Id.:
HLO
414
81,
April
11,
1994.
Unpublished.
MRID
45124401.
Ford,
L.
S.
(2000)
Hexazinone
25L:
Mouse
Bone
Marrow
Micronucleus
Assay.
DuPont
Pharmaceuticals
Company,
Safety
Assessment
Section,
Stine
Haskell
Research
Center,
P.
O.
Box
30,
Elkton
Road,
Newark,
Delaware
19714
3507.
Laboratory
Project
ID:
DuPont
3852;
Company
Study
Number:
THA
00
02
47,
April
12,
2000.
Unpublished.
Other
references:
U.
S.
EPA
Report:
Peer
Review
of
Hexazinone
(August
12,
1992).
U.
S.
EPA
Report:
RfD/
Peer
Review
Report
of
Hexazinone
(March
24,
1993).
U.
S.
EPA
Report:
Carcinogenicity
Peer
Review
of
Hexazinone.
(July
27,
1994).
U.
S.
EPA
Report:
Hexazinone
2
nd
Report
of
the
Hazard
Identification
Assessment
Review
Committee
(TXR#
0050695).
U.
S.
EPA
Report:
HEXAZINONE
Report
of
the
FQPA
Safety
Factor
Committee
(TXR#
0050750).
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
28
9.0
APPENDICES
Tables
for
Use
in
Risk
Assessment
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
29
9.1
Toxicity
Profile
Summary
Tables
9.1.1
Acute
Toxicity
Table
Acute
Toxicity
Data
on
FENBUTATIN
OXIDE
Guideline
No./
Study
Type
MRID
No.
Results
Toxicity
Category
870.1100
Acute
oral
toxicity
41235004
LD50
=
1200
mg/
kg
III
870.1200
Acute
dermal
toxicity
00104974
LD50
>
5278
mg/
kg
IV
870.1300
Acute
inhalation
toxicity
41756701
(1991)
LC50
>
3.94
mg/
L(
4
hour)
III
870.2400
Acute
eye
irritation
00106003
Irreversible
corneal
opacity
I
870.2500
Acute
dermal
irritation
00106004
Mild
IV
870.2600
Skin
sensitization
41235005
Not
a
dermal
sensitizer
in
the
Buehler
test
in
Guinea
pigs
NA
9.1.2
Subchronic,
Chronic
and
Other
Toxicity
Tables
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
870.3100
90
Day
oral
toxicity
rats
0010977
(1973)
Dose:
0,
200,
1000,
5000
ppm
(equivalent
to
0,
16.0/
16.4,
81.0/
87.3,
440/
451
mg/
kg/
day,
male/
female)
Acceptable
NOAEL
=
1000
ppm
(81.0/
87.3
mg/
kg/
day
male/
female)
LOAEL
=
5000
ppm
(440/
451
mg/
kg/
day
male/
female)
based
decreased
body
weight
and
food
efficiency.
870.3150
90
Day
oral
toxicity
in
non
rodents
00114484
(1973)
Doses
of
0,
200,
1000,
or
5000
ppm
(equivalent
to
0/
0,
5.1/
7.0,
25.9/
31.6,
122.5/
137.3
mg/
kg/
day,
males/
females)
Acceptable
NOAEL
=
1000
ppm
(equivalent
to
25.9/
31.6
mg/
kg/
day
for
males/
females).
LOAEL
=
5000
ppm
(equivalent
to
122.5/
137.3
mg/
kg/
day
in
males/
females)
based
on
decreased
body
weight
gains,
increased
relative
liver
weights,
and
increased
alkaline
phosphatase
levels
in
both
sexes
and
transiently
decreased
food
consumption
in
the
females.
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
30
870.3200
21/
28
Day
dermal
toxicity
in
rabbits
41309005
(1989)
Doses:
0,
50,
400,
or
1000
mg/
kg/
day
Acceptable
NOAEL
=
1000
mg/
kg/
day.
LOAEL
=
was
not
identified
for
systemic
and
dermal
toxicity.
870.3250
90
Day
dermal
toxicity
Not
required
870.3465
90
Day
inhalation
toxicity
The
90
day
inhalation
study
is
not
required,
however
a
28
Day
inhalation
study
is
required
(contact
Agency
prior
to
conducting
study)
870.3700a
Prenatal
developmental
in
rats
40397501
(1980)
Doses:
0,
40,
100,
400,
or
900
mg/
kg
Acceptable
Maternal
NOAEL
=
100
mg/
kg/
day
LOAEL
=
400
mg/
kg/
day
based
on
decreased
food
consumption
during
dosing
and
nominal
decreases
in
body
weight
gain
from
day
7
to
day
17
and
at
all
measured
intervals
between
and
at
900
mg/
kg/
day
on
mortality
and
decreased
body
weight
gains
and
food
consumption.
Developmental
NOAEL
=
400
mg/
kg/
day
LOAEL
=
900
mg/
kg/
day
based
on
decreased
female
fetal
weight,
and
increased
incidence
of
kidneys
with
no
papilla
(malformation),
and
an
increased
incidence
of
misaligned
sternebrae
(variation).
870.3700a
Prenatal
developmental
in
rats
00114486
(1974)
Doses:
0,
200,
1000,
or
5000
ppm
(equivalent
to
0,
18.9,
94.5,
and
482.0
mg/
kg)
Unacceptable/
Upgradable
Maternal:
NOAEL
is
1000
ppm
(equivalent
to
94.5
mg/
kg/
day).
LOAEL
=
5000
ppm
(equivalent
to
482
mg/
kg/
day)
based
on
decreased
body
weights,
body
weight
gains,
and
food
efficiency.
Developmental:
NOAEL
=
5000
ppm
(equivalent
to
482.0
mg/
kg/
day).
LOAEL
was
not
observed.
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
31
870.3700b
Prenatal
developmental
in
rabbits
00028863
(1980)
Doses:
0,
20,
50,
or
125
mg/
kg
Unacceptable/
Upgradable
Maternal
NOAEL
=
50
mg/
kg/
day
LOAEL
=
125
mg/
kg/
day
based
on
transient
decreases
in
food
consumption
and
body
weight
gains.
Developmental
NOAEL
=
50
mg/
kg/
day
LOAEL
=
125
mg/
kg/
day
based
on
possible
skeletal
abnormalities
and
total
abnormalies.
870.3800
Reproduction
and
fertility
effects
in
rats
42066501
(1991)
Acceptable
0,
200,
2000
or
5000
ppm
M:
0,
11.8,
117
or
294
mg/
kg/
day
F:
0,
14.3,
143
or
383
mg/
kg/
day
Parental/
Systemic
NOAEL
=
14.3
mg/
kg/
day
LOAEL
=
143
mg/
kg/
day
based
on
male
body
weight
decrement.
Reproductive
NOAEL
=
383
mg/
kg/
day
LOAEL
=
None
based
on
no
effects
on
or
organs
of
reproduction.
Offspring
NOAEL
=
14.3
mg/
kg/
day
LOAEL
=
143
mg/
kg/
day
based
on
reduced
female
pup
weight
at
birth
and
during
lactation.
870.4100a
Chronic
toxicity
in
rats
See
870.4300
NOAEL
=
LOAEL
=
870.4100b
Chronic
toxicity
dogs
42162301
(1991)
Doses:
0,
200,
1500,
or
6000
ppm
(equivalent
to
5.00/
4.97,
41.24/
37.6
and
161/
167
mg/
kg/
day,
male/
female.
Acceptable
NOAEL
=
200
ppm
(5.0/
5.0
mg/
kg/
day,
male/
female)
LOAEL
=
1500
ppm
(41.2
and
37.57
mg/
kg/
day,
respectively)
based
on
thinness
in
one
male
and
hepatotoxicity
as
evidenced
by
changes
in
clinical
chemistry
parameters
and
microscopic
lesions.
870.4200
Carcinogenicity
rats
See
below
870.4300
No
evidence
of
carcinogenicity
HEXAZINONE/
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May/
2002
TRED
Toxicology
Chapter
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
32
870.4200
Carcinogenicity
mice
00079203
(1981),
41359301
(1989),
42509301
(1992)
and
43202901
(1994)
Doses:
0,
0,
200,
2500
or
10,000
ppm
(equivalent
to
28/
34,
366/
450
and
1635/
1915
mg/
kg/
day,
male/
female)
Acceptable
NOAEL
=
200/
2500
ppm
(28/
450
mg/
kg/
day,
male/
female,
respectively)
LOAEL
=
2500
ppm
for
males
(equivalent
to
366
mg/
kg/
day)
based
on
gross
liver
nodules/
masses,
hyperplastic
nodules
in
the
liver
and
centrilobular
hepatocyte
hypertrophy
and
10,000
ppm
for
females
(equivalent
to
1915
mg/
kg/
day
[limit
dose])
based
on
decreased
body
weights,
increased
relative
liver/
gall
bladder
weights,
hyperplastic
nodules
and
centrilobular
hepatocyte
hypertrophy.
Insufficient
evidence
for
carcinogenicity.
870.4300
Combined
chronic/
carcinogenicity/
rats
00108638
(1977)
Doses:
0,
200,
1000,
or
2500
ppm
(equivalent
to
0,
10.2/
12.5,
53.4/
67.5,
or
138/
179
mg/
kg/
day,
male/
female)
Acceptable
NOAEL
=
200
ppm
for
males
and
females
(10.2/
12.5
mg/
kg/
day,
male/
female).
LOAEL
=
1000
ppm
for
males
and
females
(equivalent
to
53.3/
67.5
mg/
kg/
day,
male/
female)
based
on
decreased
body
weight
and
food
efficiency
in
males
and
females.
In
males
at
2500
ppm
the
body
weight
decrement
and
food
efficiency
decrement
occurred
only
for
the
first
6
months
of
the
study.
The
carcinogenic
potential
of
hexazinone
is
considered
negative.
Gene
mutation
870.5100;
Reverse
mutation
in
Salmonella
strains
40826201
(1977)
200,
400,
600,
800
and
1000
:g/
plate
S9
and
400,
800,
1200,
1600
and
2000
:g/
mL
+
S9
mix.
Unacceptable
No
mutagenic
potential
was
seen,
but
doses
insufficent
to
cause
cell
toxicity.
Gene
mutation
870.5300;
hamster
CHO
cells/
HPRT
assay
00076956
(1980)
Trial
1
were
2.0,
11.1,
13.1,
13.9
and
14.3
mM
S9
and
2.0,
7.9,
8.9,
9.3
and
9.9
mM
+S9.
Trial
2
were
2.0,
5.9,
11.1,
13.1
and
13.9
mM
S9
and
2.0,
7.9,
8.9,
9.3
and
9.9
mM
+
S9.
Acceptable
No
evidence
of
mutagenic
potential
at
cytotoxic
doses.
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
33
Cytogenics
870.5375;
Chromosomal
aberrations
in
hamster
CHO
cells
00130709
(1982)
In
Trial
1,
1.58,
3.94,
15.85
and
19.82
mM
S9
and
0.32,
3.17,
7.93
and
15.85
mM
+
S9.
In
Trial
2,
1.58,
3.94,
7.93
and
15.85
S9
0.32,
3.17,
7.93
and
15.85
mM
+
S9
Acceptable
Positive
for
structural
chromosomal
aberrations
with
and
without
S9.
Other
Effects
870.5385,
In
vivo
Rat
bone
marrow
cytogenics
assay
00131355
(1982)
Rat
doses:
100,
300
or
1000
mg/
kg
Unacceptable
No
evidence
of
mutagenic
potential,
but
insufficient
animals
and
cells
were
tested.
Other
Effects
870.5395
Mouse
bone
marrow
micronucleus
test
45124401
(2000)
Mouse
doses:
1000,
2000
and
3000
mg/
kg
Acceptable
No
evidence
of
clastogenic
or
aneugenic
effect
in
bone
marrow
at
toxic
doses..
Other
Effects
870.5550,
UDS
in
rat
hepatocytes
00130708
(1983)
Trial
1:
1
x
10
5
,
1
x
10
4
,
1
x
10
3
,
1
x
10
2
,
0.1,
1.0,
10.0
and
30.0
mM
and
Trial
2:
1
x
10
5
,
1
x
10
4
,
1
x
10
3
,
1
x
10
2
,
0.1,
1.0,
5.0,
10.0
and
30.0
mM.
Acceptable
No
evidence
of
mutagenic
potential
at
precipitating
dose
levels.
870.6200a
Acute
neurotoxicity
screening
battery
Not
required
870.6200b
Subchronic
neurotoxicity
screening
battery
Not
required
870.6300
Developmental
neurotoxicity
Not
required
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
34
870.7485
Metabolism
and
pharmacokinetics
00140162
&
00109237
(1980
&1982)
Acceptable
No
parent
was
seen
in
urine
or
feces,
which
was
rapidly
absorbed
and
excreted.
Two
identified
metabolites
resulted
from
hydroxylation
of
the
cyclohexyl
ring
and
differed
only
by
the
metabolic
conversion
of
the
6
dimethyl
amine
to
a
secondary
methyl
amine.
No
sex,
or
doserelated
differences
in
the
formation
and
excretion
of
these
metabolites
were
found.
870.7600
Dermal
penetration
Not
required
Special
studies
None
submitted
9.2
Summary
of
Toxicological
Dose
and
Endpoints
for
HEXAZINONE
for
Use
in
Human
Risk
Assessment
Exposure
Scenario
Dose
(mg/
kg/
day)
UF
/MOE
Hazard
Based
Special
FQPA
Safety
Factor
Endpoint
for
Risk
Assessment
Dietary
Risk
Assessments
Acute
Dietary
females
13
50
years
of
age
NOAEL
=
400
UF
=
1000
Acute
RfD
=
0.40
mg/
kg/
day
1x
Developmental
Toxicity
Rat
LOAEL
is
900
mg/
kg/
day
based
on
decreased
male
and
female
fetal
weight,
kidneys
with
no
papilla
(malformation)
and
misaligned
sternebrae
(variation)
Acute
Dietary
general
population
including
infants
and
children
An
appropriate
endpoint
attributable
to
a
single
dose
was
not
identified
in
the
oral
studies,
including
the
rat
and
rabbit
developmental
studies.
Chronic
Dietary
all
populations
NOAEL=
5.0
UF
=
100
Chronic
RfD
=
0.05
mg/
kg/
day
1x
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
Exposure
Scenario
Dose
(mg/
kg/
day)
UF
/MOE
Hazard
Based
Special
FQPA
Safety
Factor
Endpoint
for
Risk
Assessment
35
Incidental
Oral
Short
Term
(1
30
Days)
Residential
Only
There
are
no
residential
uses
at
the
present
time
and
therefore,
endpoints
were
not
selected.
Incidental
Oral
Intermediate
Term
(1
6
Months)
Residential
Only
There
are
no
residential
uses
at
the
present
time
and
therefore,
endpoints
were
not
selected.
Non
Dietary
Risk
Assessments
Dermal
Short
Term
(1
30
days)
No
hazard
was
identified,
therefore
quantification
of
risk
is
not
required.
No
systemic
toxicity
was
seen
at
the
limit
dose
following
repeat
dermal
application,
and
there
were
no
concerns
for
developmental
or
reproductive
toxicity.
Residential
Occupational
Dermal
Intermediate
Term
1
(1
6
Months)
Oral
NOAEL=
5.0
mg/
kg/
day
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Residential
MOE=
N/
A
N/
A
Occupational
MOE=
100
N/
A
Dermal
Long
Term
1
(1
6
Months)
Oral
NOAEL=
5.0
mg/
kg/
day
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Residential
MOE=
N/
A
N/
A
Occupational
MOE=
100
N/
A
Inhalation
Short
Term
2
(1
30
days)
Oral
NOAEL=
100
mg/
kg/
day
Developmental
Toxicity
Rat
LOAEL
=
400
mg/
kg/
day
based
on
decreases
in
maternal
food
consumption
and
dose
related
body
weight
decrement.
Residential
MOE=
N/
A
N/
A
Occupational
MOE=
100
N/
A
HEXAZINONE/
107201/
May/
2002
TRED
Toxicology
Chapter
Exposure
Scenario
Dose
(mg/
kg/
day)
UF
/MOE
Hazard
Based
Special
FQPA
Safety
Factor
Endpoint
for
Risk
Assessment
36
Inhalation
Intermediate
Term
(1
6
Months)
Oral
NOAEL=
5.0
mg/
kg/
day
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Residential
MOE
=
N/
A
N/
A
Occupational
MOE=
100
N/
A
Inhalation
Long
Term
(>
6
Months)
Oral
NOAEL=
5.0
mg/
kg/
day
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Residential
MOE=
N/
A
N/
A
Occupational
MOE=
100
N/
A
Cancer
Classification:
D
Not
Classifiable
as
to
human
carcinogenicity
1
Since
an
oral
NOAEL
was
selected
25%
dermal
absorption
factor
should
be
used
for
route
to
route
exposures.
2
Absorption
via
the
inhalation
route
is
assumed
to
be
equivalent
to
oral
absorption.
N/
A
=
Not
Applicable;
there
are
no
residential
uses.
| epa | 2024-06-07T20:31:42.870326 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0012/content.txt"
} |
EPA-HQ-OPP-2002-0188-0013 | Supporting & Related Material | "2002-09-16T04:00:00" | null | TXR#
DATE:
4/
25/
02
MEMORANDUM
SUBJECT:
HEXAZINONE
2
nd
Report
of
the
Hazard
Identification
Assessment
Review
Committee.
FROM:
David
G.
Anderson
Toxicologist.
Reregistration
Branch
2
Health
Effects
Division
(7509C)
THROUGH:
Jess
Rowland,
Co
Chair
and
Elizabeth
Doyle,
Co
Chair
Hazard
Identification
Assessment
Review
Committee
Health
Effects
Division
(7509C)
TO:
Carol
Christensen,
Risk
Assessor
Reregistration
Branch
2
Health
Effects
Division
(7509C)
PC
Code:
107201
On
Dec
4,
2001,
the
Health
Effects
Division
(HED)
Hazard
Identification
Assessment
Review
Committee
(HIARC)
reviewed
the
recommendations
of
the
toxicology
reviewer
for
HEXAZINONE
with
regard
to
the
acute
and
chronic
Reference
Doses
(RfDs)
and
the
toxicological
endpoint
selection
for
use
as
appropriate
in
occupational/
residential
exposure
risk
assessments.
The
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
HEXAZINONE
was
also
evaluated
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996.
On
April
02,
2002,
HIARC
evaluated
the
need
for
an
additional
database
uncertainty
factor
for
the
lack
of
an
acceptable
prenatal
developmental
study
conducted
in
the
rabbit
under
the
new
OPP
10X
guidance
document.
The
conclusions
drawn
at
both
meetings
are
presented
in
this
report.
2
Committee
Members
in
Attendance
Members
present
were:
Ayaad
Assaad,
Bill
Burnam,
Jonathan
Chen,
Paula
Deschamp,
Pamela
Hurley,
John
Liccione,
Elizabeth
Mendez,
David
Nixon,
Jess
Rowland,
Virginia
Fornillo
Member(
s)
in
absentia:
Beth
Doyle
Data
evaluation
prepared
by:
David
G.
Anderson,
RRB2
Also
in
attendance
were:
Sherrie
Kinard,
Ken
Dockter,
Pauline
Wagner,
Diana
Locke
Data
Evaluation/
Report
presentation
David
G.
Anderson
Toxicologist
Report
Concurrence
Brenda
Tarplee,
Senior
Scientist
Science
Information
Management
Branch
3
1.
INTRODUCTION
On
December
4,
2001,
the
Health
Effects
Division
(HED)
Hazard
Identification
Assessment
Review
Committee
(HIARC)
reviewed
the
recommendations
of
the
toxicology
reviewer
for
HEXAZINONE
with
regard
to
the
acute
and
chronic
Reference
Doses
(RfDs)
and
the
toxicological
endpoint
selection
for
use
as
appropriate
in
occupational/
residential
exposure
risk
assessments.
The
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
HEXAZINONE
was
also
evaluated
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996.
On
April
02,
2002,
HIARC
evaluated
the
need
for
an
additional
database
uncertainty
factor
for
the
lack
of
an
acceptable
prenatal
developmental
study
conducted
in
the
rabbit
under
the
new
OPP
10X
guidance
document.
The
conclusions
drawn
at
both
meetings
are
presented
in
this
report.
The
last
review
of
the
hexazinone
toxicity
data
base
was
February
11,
1993,
by
the
RfD/
Peer
Review
Committee.
A
Reregistration
Eligibility
Document
was
issued
September,
1994
(EPA
738
F
94
019).
2.
HAZARD
IDENTIFICATION
2.1
Acute
Reference
Dose
(RfD)(
Population
Subgroup:
Females
13
50)
Study
Selected:
Developmental
toxicity
Study
in
Rats
§
870.3700
MRID
No.:
40397501
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
40397501),
hexazinone
(99.26%
a.
i.;
Lot#
S30306A,
Batch#
2/
36)
in
0.5%
methylcellulose
was
administered
orally
via
gavage
to
25
Crl:
CD
®
BR
female
rats/
group
at
dose
levels
of
0,
40,
100,
400,
or
900
mg/
kg
on
gestation
day
(GD)
7
through
16.
The
dosing
volume
was
10
mL/
kg
(calculated
by
reviewers).
All
dams
were
sacrificed
on
GD
22
and
their
fetuses
removed
by
cesarean
and
examined.
When
compared
to
concurrent
controls,
no
treatment
related
changes
in
clinical
signs,
gross
pathology,
pregnancy
rate,
live
fetuses,
resorptions,
pre
or
post
implantation
loss,
corpora
lutea,
or
implantations
were
noted
at
any
dose
level
tested.
No
treatment
related
findings
were
noted
in
the
100,
or
40
mg/
kg
groups.
In
the
900
mg/
kg
dams,
one
treatment
related
death
occurred;
alopecia
and
an
enlarged
stomach
containing
fluid
and
food
were
noted
at
necropsy.
Decreased
(p<
0.05)
body
weight
gains
were
noted
during
GDs
15
17
(937%)
and
17
22
(917%).
In
addition,
body
weight
gains
were
decreased
(p<
0.05)
for
the
overall
(GDs
7
17)
treatment
interval
(930%).
Gravid
uterine
weights
were
not
reported;
however,
adjusted
(for
gravid
uterine
weight)
terminal
body
weights
were
slightly
decreased
(96%;
p#0.05).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
GDs
9
11,
15
17,
7
17,
and
17
22.
Decreased
(p#0.05)
food
consumption
was
observed
throughout
treatment
(GDs
7
17;
916
22%)
and
post
treatment
(GDs
17
22;
99%).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
GDs
7
9,
9
11,
11
13,
13
15,
15
17,
7
17,
and
17
22.
Also
a
significantly
decreased
food
consumption
was
seen
at
400
4
mg/
kg/
day
(GD9
11;
91%)
and
(GD
7
17;
98%).
In
addition,
relative
(to
body)
liver
weights
were
increased
(p#0.05)
in
the
400
(5.2%)
and
900
(5.6%)
mg/
kg
dams
compared
to
concurrent
controls
(4.9%).
Decreased
(p#0.05)
terminal
body
weights
were
noted
at
900
mg/
kg
(96%).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
relative
liver
weights
and
adjusted
terminal
body
weights.
In
addition,
a
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
absolute
liver
weights.
Despite
this
trend,
the
observed
increases
in
absolute
liver
weights
at
100,
400,
and
900
mg/
kg
(81
8%)
were
not
statistically
significant.
Liver
weight
findings
are
considered
equivocal.
The
maternal
LOAEL
is
400
mg/
kg/
day
based
on
decreased
food
consumption
during
dosing
and
nominal
decreases
in
body
weight
gain
from
day
7
to
day
17
and
at
all
measured
intervals
between
and
at
900
mg/
kg/
day
on
mortality
and
decreased
body
weight
gains
and
food
consumption.
The
maternal
NOAEL
is
100
mg/
kg/
day.
In
the
900
mg/
kg/
day
group,
male
and
female
fetal
weights
were
decreased
(921%;
p#0.05);
a
significant
(p#0.05)
trend
by
Jonckheere's
test
was
noted
for
this
parameter.
At
400
mg/
kg/
day,
only
female
fetal
weights
were
significantly
decreased
(2%)
but
were
not
considered
to
biologically
significantly
depressed.
At
900
mg/
kg/
day,
an
increased
(p#0.05)
incidence
of
misaligned
sternebra
(1),
a
variation,
was
observed
(fetal
incidence:
0.0217;
litter
incidence:
0.30)
relative
to
concurrent
controls
(fetal
incidence:
0.0066;
litter
incidence:
0.09).
In
addition,
an
increased
(p#0.05)
incidence
of
misaligned
sternebrae
(2+),
a
variation,
was
noted
(fetal
incidence:
0.0217;
litter
incidence:
0.30)
relative
to
concurrent
controls
(fetal
incidence:
0.0033;
litter
incidence:
0.04).
Furthermore,
an
increased
incidence
of
kidneys
with
no
papilla
was
observed
(fetal
incidence:
0.0347;
litter
incidence:
0.25)
relative
to
concurrent
controls
(fetal
incidence:
0.0062;
litter
incidence:
0.04).
Although
the
incidence
was
not
statistically
significant,
a
dose
related
trend
(p#0.05)
was
observed.
The
developmental
toxicity
LOAEL
is
900
mg/
kg/
day,
based
on
decreased
male
and
female
fetal
weight
and
increased
incidence
of
kidneys
with
no
papilla
(malformation),
and
an
increased
incidence
of
misaligned
sternebrae
(variation).
The
developmental
toxicity
NOAEL
is
400
mg/
kg/
day.
The
developmental
toxicity
study
in
the
rat
is
classified
acceptable/
guideline
(OPPTS
870.3700;
§83
3
a)
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
in
the
rat.
Dose
and
Endpoint
for
Establishing
RfD:
Developmental
NOAEL
is
400
mg/
kg/
day.
The
LOAEL
is
900
mg/
kg/
day
based
on
increased
kidneys
with
no
papillae
and
misaligned
sternebrae.
Uncertainty
Factor
(UF):
1000
(10X
intraspecies
variation;
10X
interspecies
extrapolation;
and
10X
additional
database
uncertainty
factor)
5
Comments
about
Study/
Endpoint/
Uncertainty
Factor:
The
malformations
(kidneys
with
no
papillae)
are
presumed
to
occur
after
a
single
and
thus
appropriate
for
acute
risk
assessment.
An
additional
database
uncertainty
factor
of
10X
is
required
for
lack
of
an
acceptable
prenatal
developmental
study
conducted
in
the
rabbit.
The
rabbit
developmental
toxicity
study
submitted
to
the
Agency
is
classified
as
unacceptable
because
of
uncertainties
in
the
effects
at
the
LOAEL
(125
mg/
kg/
day
based
on
possible
skeletal
and
total
abnormalities).
Although
this
study
is
unacceptable,
there
is
some
confidence
in
the
NOAEL
of
50
mg/
kg/
day
which
is
almost
ten
fold
lower
than
that
used
to
establish
the
acute
RfD.
A
factor
of
10X
is
necessary
(rather
than
3X)
because
when
an
additional
10X
factor
is
applied
to
the
NOAEL
of
400
mg/
kg
used
to
calculate
the
acute
RfD,
the
resulting
extrapolated
dose
is
40
mg/
kg
(400
÷
10
=
40)
which
is
comparable
to
the
rabbit
study
NOAEL
of
50
mg/
kg/
day.
Therefore,
an
additional
10X
database
uncertainty
factor
is
applied
to
the
acute
RfD
for
Females
13
50
to
account
for
the
possibility
that
a
lower
NOAEL/
LOAEL
may
be
demonstrated
in
the
rabbit.
2.2
Acute
Reference
Dose
(RfD)(
General
Population)
An
appropriate
endpoint
attributable
to
a
single
dose
was
not
identified
in
the
oral
studies,
including
the
rat
and
rabbit
developmental
studies.
2.3
Chronic
Reference
Dose
(RfD)
Study
Selected:
One
Year
Chronic
Dog
Study
Guideline
#:
870.4100
MRID
No.:
42162301
Executive
Summary:
In
a
one
year
chronic
toxicity
study,
hexazinone
(98%
a.
i.,
Lot
No.
T02118994)
was
administered
to
groups
of
5
male
and
5
female
beagle
dogs
in
the
diet
at
concentrations
of
0,
200,
1500,
or
6000
ppm
(MRID
42162301).
Time
weighted
average
doses
for
the
treated
groups
were
5.00,
41.24,
and
161.48
mg/
kg/
day,
respectively,
for
males
and
4.97,
37.57,
and
166.99
mg/
kg/
day,
respectively,
for
females.
All
animals
survived
to
scheduled
necropsy.
Treatment
related
clinical
signs
of
toxicity
included
the
observation
of
thinness
in
1/
5
mid
dose
males,
3/
5
high
dose
males,
and
1/
5
high
dose
females.
Body
weights
of
the
high
dose
groups
were
significantly
(p
#
0.05)
less
than
those
of
the
control
throughout
most
of
the
study.
Final
body
weights
of
the
high
dose
males
and
females
were
78%
and
67%,
respectively,
of
the
control
levels.
Food
consumption
by
the
high
dose
groups
was
slightly
(n.
s.)
less
than
that
of
the
controls
throughout
the
study
with
statistical
significance
(p
#
0.05)
attained
for
females
at
week
52.
Overall
food
consumption
(weeks
1
52)
for
high
dose
males
and
females
was
85%
(n.
s.)
and
74%
(p
#
0.05),
respectively,
of
the
control
group
levels.
Body
weights
and
food
consumption
for
Acute
RfD
(Females
13
50)
=
400
mg/
kg
=
0.40
mg/
kg
1000
(UF)
6
the
low
and
mid
dose
groups
were
not
affected
by
treatment.
No
treatment
related
ophthalmological
lesions,
changes
in
urinalysis
parameters,
or
gross
necropsy
findings
were
noted.
A
moderate
macrocytic
anemia
was
observed
in
the
high
dose
groups
as
evidenced
by
slight
or
significant
(p
#
0.05)
decreases
in
RBC
counts,
hemoglobin,
and
hematocrit
and
increases
in
MCV
and
MCH
in
one
or
both
sexes
throughout
the
study.
Cholesterol
levels
were
significantly
(p
#
0.05)
decreased
in
the
high
dose
groups
beginning
at
week
13
for
males
(52
64%
of
controls)
and
at
week
26
for
females
(45
51%
of
controls).
Albumin
levels
were
significantly
(p
#
0.05)
decreased
in
the
mid
dose
males
(93%
of
controls)
at
week
13
only,
and
in
the
high
dose
males
(74
78%
of
controls)
and
females
(75
82%
of
controls)
throughout
the
study.
Beginning
on
week
13
or
26,
the
high
dose
groups
had
aspartate
aminotransferase
levels
140
203%
(p
#
0.05)
of
the
control
values
and
alanine
aminotransferase
levels
206
276%
(p
#
0.05)
of
the
control
values.
Alkaline
phosphatase
levels
were
significantly
(p
#
0.05)
increased
in
the
mid
dose
males
(259
409%
of
controls)
and
females
(163
194%
of
controls;
n.
s.)
beginning
at
week
26
and
in
the
high
dose
males
(346
1363%
of
controls)
and
females
(307
559%
of
controls)
beginning
at
week
13.
For
the
high
dose
animals,
decreases
in
absolute
testes
weights
in
males
and
kidney,
heart,
and
brain
weights
in
females
(
12%)
and
increases
in
relative
liver
weights
in
males
and
females
were
considered
due
to
lower
final
body
weights
of
these
animals
as
compared
with
controls.
Microscopic
lesions
in
the
liver
of
high
dose
animals
included
concentric
membranous
bodies
in
4
males
and
5
females,
centrilobular
single
cell
necrosis
in
3
males
and
3
females,
hepatocellular
pigment
in
3
males
and
3
females,
and
vacuolation
in
3
males
and
4
females.
In
addition
vacuolation
was
observed
in
one
mid
dose
male
and
pigment
and
membranous
bodies
were
each
observed
in
one
mid
dose
female.
These
lesions
were
not
seen
in
control
or
low
dose
animals.
Therefore,
the
LOAEL
for
hexazinone
in
male
and
female
beagle
dogs
is
1500
ppm
(41.24
and
37.57
mg/
kg/
day,
respectively)
based
on
thinness
in
one
male
and
hepatotoxicity
as
evidenced
by
changes
in
clinical
chemistry
parameters
and
microscopic
lesions.
The
NOAEL
is
200
ppm
(5.00
and
4.97
mg/
kg/
day,
respectively).
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
guideline
requirements
for
a
chronic
toxicity
study
[OPPTS
870.4100
(§
83
1b)]
in
dogs.
Dose
and
Endpoint
for
Establishing
RfD:
NOAEL
of
5.0
mg/
kg/
day.
The
LOAEL
is
38
mg/
kg/
day
based
on
elevated
clinical
chemistry
values
(serum
alkaline
phosphatase,
serum
aspartate
aminotransferase),
other
changes
in
clinical
chemistry
values,
liver
microscopic
findings
and
body
weight
decrement
and
clinical
observation
of
thinnest
in
one
male
(4
of
10
males
and
females
at
the
next
higher
dose).
7
Uncertainty
Factor(
s):
100
Comments
about
Study/
Endpoint/
Uncertainty
Factor(
s):
The
study
is
of
the
appropriate
duration.
The
RfD/
peer
Review
Committee
chose
the
same
value
in
1994,
which
formed
the
basis
of
the
Chronic
RfD
for
the
1994
RED.
An
additional
database
uncertainty
factor
to
account
for
the
lack
of
an
acceptable
rabbit
developmental
study
is
not
necessary
when
assessing
chronic
dietary
exposure
since
the
NOAEL
of
5.0
mg/
kg/
day
in
the
dog
used
to
establish
the
chronic
RfD
is
ten
fold
below
that
seen
in
the
rabbit
study
and
is
considered
to
be
adequately
protective.
2.4
Occupational/
Residential
Exposure
2.4.1
Short
Term
(1
Day
1
Month)
and
Intermediate
Term
(1
Month
6
Months)
Incidental
Oral
Exposure
Toxicity
endpoints
for
incidental
oral
exposure
were
not
selected
since
there
are
no
residential
exposure
based
on
the
current
use
pattern
and
none
is
anticipated
in
the
future.
2.4.2
Dermal
Absorption
No
dermal
absorption
study
is
available.
For
dermal
absorption,
the
NOAEL
from
the
21
day
dermal
toxicity
study
at
the
limit
dose
of
1000
mg/
kg/
day
was
considered
a
lower
bound
for
the
LOAEL,
which
was
compared
with
LOAEL
of
250
mg/
kg/
day
from
the
range
finding
rabbit
study
(MRID#
00028863).
The
ratio
of
these
two
numbers
was
used
to
estimate
a
dermal
absorption
factor
of
25%.
The
range
finding
study
was
chosen
instead
of
the
main
rabbit
developmental
toxicity
study
(MRID#
00028863)
for
comparison
because
the
main
study
was
considered
to
be
unacceptable
for
regulatory
purposes.
Dermal
Absorption
Factor:
25%
Comments
about
Study/
Endpoint:
The
use
of
a
25%
dermal
absorption
factor
for
route
to
route
extrapolation
of
oral
studies
to
occupational
dermal
exposure
would
be
protective
of
the
developmental
effects
seen
in
the
rat
study.
2.4.3
Short
Term
Dermal
(1
Day
1
Month)
Exposure
Chronic
RfD
=
5.0
mg/
kg/
day
(NOAEL)
=
0.05
mg/
kg/
day
100
(UF)
8
Study
Selected:
None
MRID
No.:
None
Executive
Summary:
None
Dose
and
Endpoint
for
Risk
Assessment:
Not
applicable
Comments
about
Study/
Endpoint:
No
hazard
and
no
quantification
required.
There
were
no
systemic
effects
at
1000
mg/
kg/
day,
limit
dose,
in
the
21
day
dermal
study
in
rabbits
(MRID#
41309005).
The
oral
developmental
NOAEL
(400
mg/
kg/
day)
in
conjunction
with
the
use
of
25%
dermal
absorption
factor
yields
a
dermal
equivalent
dose
of
1600
mg/
kg/
day
[(
400/
0.25)=
1600
mg/
kg/
day],
which
is
higher
than
the
limit
dose
in
the
rabbit
21
day
dermal
study
and
thus
would
address
the
concerns
for
developmental
toxicity
seen
at
900
mg/
kg/
day.
2.4.4
Intermediate
Term
Dermal
(1
6
Months)
and
Long
Term
Dermal
(longer
than
6
Months)
Exposure
Study
Selected:
Chronic
Feeding
Study
in
Dogs
§
870.4100
MRID
No.:
42162301
Executive
Summary:
[See
Section
2.3
on
the
Chronic
Reference
Dose
(RfD).]
Dose/
Endpoint
for
Risk
Assessment:
NOAEL
is
based
on
elevated
clinical
chemistry
values
(serum
alkaline
phosphatase,
serum
aspartate
aminotransferase),
other
changes
in
clinical
chemistry
values,
liver
microscopic
findings
and
body
weight
decrement
and
the
clinical
observation
of
thinnest
in
one
males
at
38
mg/
kg/
day.
Comments
about
Study/
Endpoint:
The
elevation
in
clinical
chemistry
parameters
were
seen
at
3
and
6
months
and
thus
appropriate
for
the
exposure
period.
Since
an
oral
NOAEL
was
selected,
a
25%
dermal
absorption
factor
should
be
used
for
route
to
route
extrapolation.
2.4.5
Short
Term
Inhalation
Exposure
(1
day
to
1
Month)
Study
Selected:
Developmental
Toxicity
in
the
Rat
§
870.3700
MRID
No.:
40397501
Executive
Summary:
[See
Section
2.1
Acute
Reference
Dose
(RfD).]
Dose/
Endpoint
for
Risk
Assessment:
The
maternal
NOAEL
of
100
mg/
kg/
day
based
on
based
on
maternal
body
weight
and
food
consumption
decrement
at
400
mg/
kg/
day.
9
Comments
about
Study/
Endpoint:
In
the
absence
of
a
inhalation
study
an
oral
NOAEL
was
selected.
Absorption
via
the
inhalation
route
is
assumed
to
be
equivalent
to
oral
absorption.
2.4.6
Intermediate
Term
inhalation
(1
Month
to
6
Months)
and
Long
Term
Inhalation
(longer
than
6
Months)
Exposure.
Study
Selected:
Chronic
Feeding
Study
in
Dogs
§
870.4100
MRID
No.:
42162301
Executive
Summary:
[See
Section
2.3
on
the
Chronic
Reference
Dose
(RfD).]
Dose/
Endpoint
for
Risk
Assessment:
NOAEL
of
5.0
mg/
kg/
day
based
on
elevated
clinical
chemistry
values
(serum
alkaline
phosphatase,
serum
aspartate
aminotransferase),
other
changes
in
clinical
chemistry
values,
liver
microscopic
findings
and
body
weight
decrement
and
clinical
observation
of
thinnest
in
one
males
at
38
mg/
kg/
day.
Comments
about
Study/
Endpoint:
The
affects
seen
in
clinical
chemistry
values
at
3,
6
and
12
months
are
appropriate
for
these
exposure
periods.
Absorption
via
the
inhalation
route
is
presumed
to
be
equivalent
to
oral
absorption.
2.5
Margins
of
Exposure
for
Occupational/
Residential
Risk
Assessment
A
margin
of
exposure
of
100
is
adequate
for
occupational
dermal
and
inhalation
exposure.
There
is
no
non
occupational
(residential)
exposures
identified
at
this
time.
2.6
Recommendation
for
Aggregate
Exposure
Risk
Assessments
Aggregate
exposure
risk
assessment
is
not
required
since
there
are
no
non
occupational
(residential)
uses
at
the
present
time.
3.
CLASSIFICATION
OF
CARCINOGENIC
POTENTIAL
3.1
Combined
Chronic
Toxicity/
Carcinogenicity
Study
in
Rats
MRID
No.:
00108638
Executive
Summary:
In
this
combined
chronic/
oncogenicity
study
(MRID
00108638),
hexazinone
(94
96%
a.
i.;
Lot/
Batch
#:
6897
40
and
74.25)
was
administered
in
the
diet
to
ChR
CD
rats
(36/
sex/
group)
for
up
to
25
months
at
nominal
doses
of
0,
0,
200,
1000,
or
2500
ppm
(equivalent
to
0,
0,
10.2,
53.4,
and
138.3
mg/
kg/
day
in
males
and
0,
0,
12.5,
67.5,
and
178.6
mg/
kg/
day
in
females).
10
No
treatment
related
differences
were
observed
in
mortality,
clinical
signs,
food
consumption,
hematology,
clinical
chemistry,
organ
weights,
and
gross
or
microscopic
pathology.
No
adverse
effects
were
observed
in
the
200
ppm
animals.
There
were
several
signs
of
general
toxicity,
but
a
target
organ
could
not
be
clearly
identified
at
any
dose.
Terminal
body
weights
were
decreased
8%
in1000
ppm
and
20%,
p#0.05,
in
the
2500
ppm
females.
A
decrease
in
overall
body
weight
gain
(Days
0
728;
calculated
by
the
reviewers)
was
also
observed
in
the
1000
(
10%)
and
2500
ppm
(
25%)
females.
Nominal
decreases
in
body
weight
and
body
weight
gain
(
3
to
5%)
occurred
in
males
at
1000
ppm
during
the
study,
which
may
have
been
biologically
significant
at
the
end
of
the
study
(
12%
body
weight
and
14%
for
body
weight
gain).
Decreases
(p
values
not
calculated)
in
total
food
efficiency
were
observed
in
females
at
1000
(
10%)
and
2500
ppm
(
25%)
and
in
males
at
1000
ppm
during
the
study
with
overall
decrement
in
food
efficiency
in
1000
ppm
males
(
10%).
In
males
at
2500
ppm,
food
efficiency
was
depressed
for
the
first
6
months
of
the
study
(
25%),
but
from
6
months
to
the
end
of
the
study,
it
was
increased
139%.
The
reviewer
noted
problems
interpreting
the
body
weights
and
food
efficiency
in
males
at
the
top
dose
level,
which
were
not
consistent
with
the
mid
dose
level.
For
the
first
6
months
of
the
study
in
males,
a
body
weight
decrement
due
to
probable
toxicity
was
seen
at
1000
and
2500
ppm.
After
6
months
food
efficiency
in
males
at
the
1000
ppm
remained
less
than
controls
(
56%)
while
food
efficiency
at
2500
ppm
in
males
was
higher
than
controls
(+
139%)(
Table
4).
By
the
end
of
the
study,
male
body
weight
at
1000
ppm
was
12%
and
body
weight
gain
14%,
where
as
body
weight
and
body
weight
gain
in
males
at
2500
ppm
was
+3%
for
both
weight
and
gain.
The
reason
for
this
recovery
in
male
body
weight
decrement
at
2500
ppm
is
unknown,
but
it
appears
to
be
real.
[Since
absolute
and
relative
liver
weights
were
decreased
in
males
at
2500
ppm,
liver
enzyme
induction
allowing
the
recovery
seems
unproven.]
The
body
weight
decrement
at
1000
and
2500
ppm
with
recovery
in
body
weight
at
2500
ppm
indicates
the
an
adequate
dose
level
to
test
for
carcinogenicity
in
males
was
approached,
but
probably
not
attained.
Other
treatment
groups
were
similar
to
the
average
of
concurrent
controls.
Dosing
was
considered
adequate
based
on
decreased
body
weights,
body
weight
gains,
and
food
efficiency
in
the
2500
and
1000
ppm
females
and
food
efficiency
and
body
weights
in
the
2500
ppm
males
for
the
first
6
months.
Body
weight
(
12%)
and
body
weight
gain
(
14%)
in
males
at
1000
ppm
were
decreased
at
the
end
of
the
study,
in
addition
overall
food
efficiency
(
14%)
was
decreased
by
the
end
of
the
study.
Thus
female
body
weight
and
body
weight
gain
was
decreased
sufficiently
to
adequately
test
for
carcinogenicity.
Male
body
weight
and
body
weight
gain
at1000
ppm
appeared
to
be
adequate
to
test
for
carcinogenicity
by
the
end
of
the
study,
but
the
lack
of
dose
response
in
male
body
weight
and
body
11
weight
gain
at
2500
ppm
(showing
recovery
after
6
months
such
that
body
weight
and
body
weight
gain
were
higher
than
control
values)
may
indicate
problems
with
the
interpretation
of
the
body
weights
and
body
weight
gains
at
1000
ppm.
In
the
2500
ppm
males,
creatinine
was
increased
(NS)
in
the
urine
at
months
18
and
24
and
bilirubin
was
detected
at
month
18
and
24.
The
Sponsor
reported
that
the
urine
was
more
alkaline
in
the
2500
ppm
treatment
groups
(data
not
reported).
Also
at
2500
ppm,
decreased
(p#0.05)
absolute
and
relative
liver
and
kidney
organ
weights
were
observed
in
the
males
and
increased
(p#0.05)
relative
(to
body)
stomach
and
kidney
organ
weights
were
observed
in
the
females.
However,
histopathological
data
did
not
corroborate
these
findings.
The
LOAEL
is
1000
ppm
for
males
and
females
(equivalent
to
53.3
for
males
and
67.5
mg/
kg/
day
for
females)
based
on
decreased
body
weight
and
food
efficiency
in
males
and
females.
In
males
at
2500
ppm
the
body
weight
decrement
and
food
efficiency
decrement
occurred
only
for
the
first
6
months
of
the
study.
The
NOAEL
is
200
ppm
for
males
and
females
(10.2
for
males
and
12.5
mg/
kg/
day
for
females).
Neoplasm
data
were
evaluated
by
two
pathologists.
An
increase
incidence
of
thyroid
C
cell
adenomas
was
observed
in
the
2500
ppm
males,
but
when
analyzed
by
the
Fisher's
exact
test
(p>
0.10)
or
life
table
methods
(p>
0.20)
no
significant
differences
were
observed
between
controls
and
treated
groups.
Using
life
table
analyses
a
significant
(p<
0.05)
dose
response
trend
was
observed
in
thyroid
C
cell
tumors
in
only
one
of
the
two
pathology
reports.
Female
rats
did
not
show
any
potential
for
C
cell
thyroid
adenomas.
The
incidence,
malignancy
and
latency
of
tumors
were
comparable
among
control
and
treated
rats
of
both
sexes.
Under
the
conditions
of
this
study,
carcinogenic
potential
of
hexazinone
is
considered
negative.
The
submitted
study
is
classified
as
acceptable
for
guideline
870.4300
combined
chronic/
carcinogenicity
study
in
rats.
Discussion
of
Tumor
Data:
Neoplasm
data
were
evaluated
by
two
pathologists.
An
increase
incidence
of
thyroid
C
cell
adenomas
was
observed
in
the
2500
ppm
males,
but
when
analyzed
by
the
Fisher's
exact
test
(p>
0.10)
or
life
table
methods
(p>
0.20)
no
significant
differences
were
observed
between
controls
and
treated
groups.
Using
life
table
analyses
a
significant
(p<
0.05)
dose
response
trend
was
observed
in
thyroid
C
cell
tumors
in
only
one
of
the
two
pathology
reports.
Female
rats
did
not
show
any
potential
for
C
cell
thyroid
adenomas.
The
incidence,
malignancy
and
latency
of
tumors
were
comparable
among
control
and
treated
rats
of
both
sexes.
The
study
in
rats
does
not
support
a
carcinogenic
potential
for
hexazinone.
Adequacy
of
the
Dose
Levels
Tested:
The
dose
levels
in
female
rats
was
adequate
to
test
for
the
carcinogenic
potential
hexazinone.
There
was
an
adequate
body
weight
decrement
and
body
weight
12
gain
decrement
at
the
two
top
dose
levels.
The
dose
levels
in
male
rats
approached
an
adequate
dose
level
to
test
for
carcinogenic
potential
of
hexazinone.
There
may
have
been
an
adequate
body
weight
and
body
weight
gain
at
the
mid
dose
level
at
the
end
of
the
study
to
test
for
carcinogenic
potential
of
hexazinone,
however
body
weights
of
males
at
the
top
dose
level
behaved
atypically.
At
the
top
dose
level,
males
showed
a
adequate
body
weight
decrement
only
for
the
first
6
months
of
the
study
and
by
the
end
of
the
study,
body
weights
were
higher
than
the
average
of
the
two
controls.
The
reason
for
this
reversible
body
weight
decrement
is
unknown,
but
the
top
dose
level
in
males
was
one
half
the
top
dose
level
of
5000
ppm
in
the
90
day
subchronic
study
in
males
where
liver
toxicity
was
seen.
These
body
weight
decrements
in
males
and
females
are
supported
by
a
corresponding
decrements
in
food
efficiency.
3.2
Carcinogenicity
Study
in
Mice
MRID
No.
41359301,42509301
and
4320290
§
870.4200
Executive
Summary:
In
this
mouse
oncogenicity
study
(MRIDs
00079203,
41359301,
42509301
and
43202901),
hexazinone
($95%
a.
i.;
Lot/
Batch
#:
H
11,
265
and
265
2)
was
administered
in
the
diet
to
CD
1
mice
(80/
sex/
group)
for
up
to
104
weeks
at
nominal
doses
of
0,
200,
2500
or
10,000
ppm
(equivalent
to
28,
366
and
1635
mg/
kg/
day
in
males
and
0,
34,
450
and
1915
mg/
kg/
day
in
females).
No
treatment
related
differences
were
observed
in
mortality,
food
consumption,
food
efficiency
or
hematology.
Hepatotoxicity
was
evident
at
the
terminal
sacrifice.
Macroscopic
liver
nodule/
mass
(%
treated
vs
%
controls;
n
=
28
55)
was
observed
in
males
at
2500
(39%
vs
7%)
and
10,000
ppm
(33%).
Increased
incidences
(%
treated
vs
0%
controls;
n
=
38
55)
in
the
following
microscopic
liver
lesions
were
observed:
hyperplastic
nodule(
s)
(includes
both
foci
of
cellular
alteration
and
adenoma)
in
males
at
2500
(39%
vs
20%)
and
10,000
ppm
(36%)
and
in
females
at
10,000
ppm
(15%
vs
3%);
and
necrosis
(severity
and
type
unspecified)
in
the
10,000
ppm
males
(36%
vs
7%).
Centrilobular
hepatocyte
hypertrophy
was
observed
(%
treated
vs
%
controls)
at
the
terminal
sacrifice
(n
=
38
55)
in
males
at
2500
(18%
vs
0%)
and
10,000
ppm
(98%)
and
in
females
at
10,000
ppm
(46%
vs
0%)
and
in
the
dead
and
moribund
males
(n
=
25
40)
at
2500
(44%
vs
0%)
and
10,000
ppm
(60%).
Increased
(p#0.05
or
0.01)
liver/
gall
bladder
weights
were
observed
at
10,000
ppm
in
males
in
both
absolute
and
relative
to
body
weights
and
in
females
in
relative
to
body
weight.
Other
signs
of
toxicity
were
evident.
Distal
tail
tip
sloughing
and/
or
discoloration
was
observed
at
10,000
ppm
in
males
at
Weeks
13
104
and
in
females
at
Weeks
5
and
13
104.
Macroscopically,
tip
of
tail
missing/
sloughed
was
observed
at
the
terminal
sacrifice
in
the
10,000
ppm
males
(31%
vs
5%)
and
females
(61%
vs
11%)
and
in
the
dead
and
moribund
10,000
ppm
females
(46%
vs
2%).
The
toxicological
significance
of
these
findings
was
unclear.
Minor
decreases
(p#0.05
or
0.01)
in
body
13
weights
were
observed
in
the
10,000
ppm
treatment
groups
at
Weeks
13
104
in
both
sexes.
Overall
body
weight
gains
(calculated
by
the
reviewers)
were
decreased
in
the
10,000
ppm
males
(925%)
and
females
(931%).
The
LOAEL
is
2500
ppm
for
males
(equivalent
to
366
mg/
kg/
day)
based
on
gross
liver
nodules/
masses,
hyperplastic
nodules
in
the
liver
and
centrilobular
hepatocyte
hypertrophy
and
10,000
ppm
for
females
(equivalent
to
1915
mg/
kg/
day
[limit
dose])
based
on
decreased
body
weights,
increased
relative
liver/
gall
bladder
weights,
hyperplastic
nodules
and
centrilobular
hepatocyte
hypertrophy.
The
NOAEL
is
200
ppm
(equivalent
to
28
mg/
kg/
day)
for
males
and
2500
ppm
(equivalent
to
450
mg/
kg/
day)
for
females.
Liver
samples
were
first
evaluated
using
the
term
hyperplastic
nodule
which
did
not
clearly
distinguish
neoplasia
from
non
neoplasia.
Reevaluation
was
conducted
to
make
this
distinction,
and
no
significant
differences
were
observed
between
the
treatment
groups
and
the
concurrent
controls.
However
positive
trends
(p<
0.05)
were
observed
(%
treated
vs
%
controls)
in
focus/
foci
of
cellular
alteration
in
males,
hepatocellular
neoplasm(
s)
(including
adenoma,
sarcoma,
carcinoma,
leukemia,
and
lymphoma)
in
females,
and
singular
hepatocellular
adenoma
in
females.
Focus/
foci
of
cellular
alteration
were
observed
in
males
at
2500
(11.3%
vs
5.0%)
and
10,000
ppm
(24.1%)
and
females
at
10,000
ppm
(12.5%
vs
3.8%)
beginning
at
Week
57.
Singular
hepatocellular
adenoma
was
observed
in
the
10,000
ppm
females
(7.5%
vs
2.5%)
beginning
at
Week
77.
Hepatocellular
neoplasm(
s)
were
observed
in
the
10,000
ppm
females
(8.8%
vs
2.5%).
A
carcinoma
in
the
10,000
ppm
treatment
groups
was
first
observed
at
Week
65.
The
incidence
of
carcinomas
were
within
historical
control
ranges
for
each
sex,
while
the
incidence
of
adenomas
were
increased
by
3.21%
in
the
10,000
ppm
females.
A
dosedependent
increase
in
adenomas
was
not
observed
in
males.
The
Health
Effects
Division
Carcinogenicity
Peer
Review
Committee
(CPRC)
concluded
that
hexazinone
should
be
classified
as
a
Group
D
(not
classifiable
as
to
human
carcinogenicity)(
7/
27/
94).
Under
the
conditions
of
this
study,
evidence
of
carcinogenic
potential
was
equivocal:
a
positive
trend
test
for
neoplasia
was
observed
in
female
mice,
but
no
significant
difference
was
determined
by
pair
wise
comparison.
The
submitted
study
is
classified
as
acceptable
for
guideline
870
4200
carcinogenicity
study
in
mice.
Discussion
of
Tumor
Data:
A
dose
dependent
increase
in
adenomas
was
not
observed
in
males.
Under
the
conditions
of
this
study,
evidence
of
carcinogenic
potential
was
equivocal:
a
positive
trend
test
for
neoplasia
was
observed
in
female
mice,
but
no
significant
difference
was
determined
by
pairwise
comparison.
Adequacy
of
the
Dose
Levels
Tested:
Adequate
dose
levels
were
used
in
male
and
female
mice
to
test
for
the
carcinogenic
potential
of
hexazinone.
Liver
toxicity
was
seen
at
the
top
dose
level
in
males
and
females.
3.3
Classification
of
Carcinogenic
Potential
HED's
Carcinogenicity
Peer
Review
Committee
classified
hexazinone
as
a
Group
D
Chemical
(not
14
classifiable
as
to
human
carcinogenicity)
(7/
27/
94).
This
classification
was
based
on
the
following
weight
of
evidence
considerations.
In
rats,
females
showed
no
evidence
for
carcinogenicity;
males
showed
a
significant
trend
only
for
thyroid
adenomas.
In
mice,
the
evidence
of
carcinogenicity
was
equivocal:
a
positive
trend
test
for
liver
tumors
was
observed
in
female
mice,
but
no
significant
difference
was
seen
by
pair
wise
comparison
(CPRC
Report
dated
July
27,
1994).
4.
MUTAGENICITY
The
required
mutagenicity
testing
is
complete.
This
section
was
copied
from
the
1994
RED
for
Hexazinone
and
the
updated
DERs.
One
mutagenicity
study
was
submitted
since
the
1994
RED
was
written;
a
negative
in
vivo
mammalian
micronucleus
test
in
mouse
bone
marrow
cells
(MRID#
45124401).
Hexazinone
was
found
to
be
positive
for
mutagenicity
in
one
chromosomal
aberration
assay
(in
vitro
cytogenics)
(MRID#
00130709),
but
negative
in
the
remaining
studies.
It
is
concluded
that
the
test
material
was
clastogenic
in
both
of
the
nonactivated
trials
and
was
also
clastogenic
in
the
one
adequate
S9
activated
trials.
Under
both
test
conditions,
concentrations
providing
evidence
of
clastogenicity
induced
an
acceptable
level
of
cytotoxicity
(>
50%
relative
cell
survival).
Thus,
the
findings
can
not
be
considered
to
be
a
secondary
effect
of
cytotoxicity.
Nevertheless,
the
outcome
of
the
induced
structural
damage
(i.
e.,
primarily
chromatid
and
chromosome
breaks)
is
unclear
since
these
types
of
structural
aberrations
would
not
likely
be
passed
on
to
daughter
cells.
Because
unambiguous
positive
results
were
achieved,
it
was
concluded
that
the
study
provided
adequate
evidence
that
INA
3674
112
(hexazinone,
technical)
is
clastogenic
in
an
acceptable
study.
Guideline
870.5100
Gene
Mutation
Assay
in
Ames
Test:
Hexazinone
was
tested
with
metabolic
activation
(rat
liver
microsomal
fraction
commonly
known
as
S
9
fraction,
plus
cofactors)
at
concentrations
ranging
from
400
to
2000
ug/
plate
and
without
metabolic
activation
at
concentrations
ranging
from
200
to
1000
ug/
plate.
The
strains
of
Salmonella
typhimurium
used
were
TA1535,
TA1537,
TA1538,
TA98
and
TA100.
No
increases
in
reverse
mutations
were
observed
at
any
concentration.
Positive
results
were
obtained
with
standard
reference
mutagens
(positive
controls)(
MRID
00098982).
Guideline
870.5100
Reverse
mutation
assay:
In
a
reverse
gene
mutation
assay
in
bacteria
(MRID
40826201),
strains
TA98,
TA100,
TA1535,
TA1537
and
TA1538
of
S.
typhimurium
were
exposed
to
Striazine
2,4(
1H,
3H)
dione,
3
cyclohexyl
6
dimethylamino
1
methyl
(95%
a.
i.)
in
ethanol
at
concentrations
of
200,
400,
600,
800
and
1000
:g/
plate
without
mammalian
metabolic
activation
(S9
mix)
and
at
concentrations
of
400,
800,
1200,
1600
and
2000
:g/
mL
with
S9
mix.
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
male
Crl:
CD(
SD)
BR
rat
liver.
The
maximum
concentrations
of
S
triazine
2,4(
1H,
3H)
dione,
3
cyclohexyl
6
dimethylamino
1
methyl
tested
produced
little
or
no
cytotoxicity,
were
not
limited
by
solubility
and
were
not
a
limit
dose
for
the
assay.
No
statistically
significant
increases
in
the
number
of
revertants
per
plate
or
positive
linear
dose
response
were
seen.
The
solvent
and
positive
controls
induced
acceptable
responses
in
the
corresponding
strains.
There
was
no
evidence
of
induced
mutant
colonies
over
background.
15
This
study
is
classified
as
Unacceptable.
It
does
not
satisfy
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5100
(§
84
2)]
for
in
vitro
mutagenicity
[bacterial
reverse
gene
mutation]
data
and
should
be
repeated
using
higher
doses.
Guideline
870.5300:
Gene
Mutation
Assay
in
Mammalian
Cells:
In
a
mammalian
cell
gene
mutation
assay
at
the
HGPRT
locus
(MRID
No.
00076956),
Chinese
hamster
CHO
K1
BH4
cells
cultured
in
vitro
were
exposed
to
INA
3674
112,
(Lot
No.
7612
5E6E,
95%
a.
i.)
in
ethanol
in
two
trials.
Concentrations
used
in
Trial
1
were
2.0,
11.1,
13.1,
13.9
and
14.3
mM
under
nonactivated
conditions
and
concentrations
of
2.0,
7.9,
8.9,
9.3
and
9.9
mM
under
activated
conditions
(S9
mix).
Concentrations
used
in
Trial
2
were
2.0,
5.9,
11.1,
13.1
and
13.9
mM
without
S9
mix
and
concentrations
of
2.0,
7.9,
8.9,
9.3
and
9.9
mM
with
S9
mix.
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
male
Charles
River
CD®
rat
livers.
INA
3674
112
was
tested
up
to
cytotoxic
concentrations.
In
Trial
1,
the
cultures
treated
at
14.3
mM
S9
were
not
plated
for
mutation
determination
due
to
cytotoxicity
in
both
Trials
1
and
2.
Cytotoxicity
was
also
noted
at
9.9
mM
+S9.
No
statistically
significant
increases
in
mutant
frequency
over
solvent
control
values
were
seen
with
or
without
S9
mix
in
either
Trial
1
or
2.
The
expected
marked
increase
in
the
mutation
were
seen
with
the
positive
controls.
There
was,
however,
no
indication
that
INA
3674
112
induced
a
mutagenic
effect
either
in
the
presence
or
the
absence
of
S9
activation.
This
study
is
classified
as
acceptable.
It
satisfies
the
requirement
for
FIFRA
Test
Guideline
OPPTS
[870.5300
(§
84
2)]
for
in
vitro
mutagenicity
(mammalian
forward
gene
mutation)
data.
Guideline:
870.5395
Mouse
bone
marrow
micronucleus
assay:
In
a
Crl:
CD
1
(ICR)
BR
mouse
bone
marrow
micronucleus
assay
(MRID
45124401),
5
mice/
sex/
dose/
harvest
time
were
treated
orally
with
Hexazinone
25L
(Lot
No.
9912033,
25%
Hexazinone
a.
i.
(24.5%
by
analysis)
and
75%
inert
ingredients)
at
doses
of
1000,
2000
and
3000
mg/
kg.
Bone
marrow
cells
were
harvested
at
24
and
48
hours
post
treatment
and
examined
for
micronucleated
polychromatic
erythrocytes
(MPCEs).
The
vehicle
was
Milli
Q
®
water.
Signs
of
toxicity
noted
at
3000
mg/
kg
included:
death,
convulsions,
half
shut
eyes,
head
tilt,
irregular
respiration,
lethargy,
low
carriage,
pallor,
prostration,
uncontrollable
spinning,
shovel
nosing,
straining
up
on
toes
and
tremors.
Micronuclei
were
scored
in
bone
marrow
from
mice
treated
at
3000
mg/
kg
and
from
the
solvent
and
positive
controls.
Mice
from
the
two
lower
dose
groups
were
not
evaluated
for
micronuclei
induction.
No
statistically
significant
increases
in
the
frequency
of
MPCEs
or
in
the
PCE/
NCE
ratio
over
the
solvent
control
values
were
seen
in
either
sex
at
either
the
24
or
48
hour
harvest
time.
The
solvent
and
positive
control
values
were
appropriate
and
within
the
testing
laboratory's
historical
control
ranges.
There
was
no
evidence
that
Hexazinone
25L
induced
a
clastogenic
or
aneugenic
effect
in
bone
marrow
at
any
harvest
time.
This
study
is
classified
as
Acceptable/
Guideline.
It
satisfy
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5395
(§
84
2)]
for
in
vivo
cytogenetic
mutagenicity
data.
16
Guideline
870.5375
Structural
Chromosome
Aberration
Assay;
In
vitro
Cytogenetic
Assay:
In
a
mammalian
cell
cytogenetics
assay
(MRID
No.
00130709),
Chinese
hamster
ovary
CHO
K1
BH4
cell
cultures
were
exposed
to
INA
3674
112
(Hexazinone,
95%
a.
i.)
in
ethanol
in
two
separate
trials.
Exposure
was
for
two
hours
with
activation
and
for
10
hours
without
activation.
Cells
were
harvested
10
hours
after
the
start
of
treatment.
In
Trial
1,
cells
were
treated
at
concentrations
of
1.58,
3.94,
15.85
and
19.82
mM
without
metabolic
activation
(S9
mix)
and
at
concentrations
of
0.32,
3.17,
7.93
and
15.85
mM
with
S9
mix.
In
Trial
2,
cells
were
treated
at
concentrations
of
1.58,
3.94,
7.93
and
15.85
without
S9
mix
and
at
concentrations
of
0.32,
3.17,
7.93
and
15.85
mM
with
S9
mix.
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
CD
rat
livers.
INA
3674
112
was
tested
up
to
cytotoxic
concentrations.
Based
on
the
results
of
a
preliminary
cytotoxicity
test,
upper
concentrations
of
23.78
mM
without
S9
mix
and
47.56
mM
with
S9
mix
were
selected
for
the
first
cytogenetic
assay
but
these
concentrations
proved
excessively
cytotoxic
and
were
not
scored
for
chromosomal
aberrations.
Without
S9
activation,
statistically
significant
increases
(p<
0.01)
in
structural
aberrations
per
cell
(excluding
gaps),
lesions
per
cell
and
percent
abnormal
cells
were
seen
at
15.85
mM
(Trials
1
and
2)
and
19.82
mM
(tested
in
Trial
1
only).
Relative
percent
survival
(RPS)
at
this
level
was
.50%.
The
percent
abnormal
cells
averaged
over
all
cultures
from
both
trials
was
28.0%
and
21.5%
at
19.82
and
15.85
mM,
respectively,
compared
to
the
solvent
control
values
of
2.0%
(0.5%
ethanol
in
Trial
2)
and
7.0%
(0.75%
ethanol
in
Trial
1).
The
percent
abnormal
cells
in
positive
control
cultures
was
18%
in
both
Trial
1
(4.83
mM
EMS)
and
Trial
2
(6.44
mM
EMS).
In
the
presence
of
S9
mix,
no
statistically
significant
increases
in
chromosomal
aberration
induction
were
seen
in
Trial
1;
however,
very
low
positive
control
values
indicated
a
problem
with
the
S9
mix.
Statistically
significant
increases
were
seen
at
15.85
mM
in
Trial
2;
RPS
at
15.85
mM
was
75%.
There
was
a
statistically
significant
dose
related
trend
for
all
three
parameters.
The
statistically
significant
(p
<0.01)
increases
at
15.85
mM
remained
when
the
data
from
Trial
1
and
2
were
combined
(average
of
20%
abnormal
cells
compared
to
10%
for
the
solvent
control).
The
predominant
aberrations
with
or
without
S9
mix
were
chromatid
and
isochromatid
breaks.
Solvent
and
positive
controls
(except
the
positive
control
in
Trial
1
with
S9
mix)
induced
the
appropriate
responses.
INA
3674
112
was
positive
for
the
induction
of
structural
chromosomal
aberrations
in
both
the
presence
and
absence
of
S9
mix.
This
study
is
classified
as
Acceptable/
guideline
and
satisfies
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5375
(§
84
2)]
for
in
vitro
cytogenetic
mutagenicity
data.
Guideline
870.5385
Structural
Chromosome
Aberration
Assay;
In
vivo
Cytogenetic
Assay:
In
a
mammalian
cell
cytogenetics
assay
(MRID
00131355),
in
bone
marrow
cells
of
Sprague
Dawley
CD
rats,
three
rats/
dose/
sex/
harvest
time
were
exposed
to
H#
14,555
in
corn
oil
(
assumed
100%
a.
i.)
at
doses
of
100,
300
and
1000
mg/
kg
by
oral
gavage.
Bone
marrow
cells
were
harvested
at
6,
12,
24
and
48
hours
posttreatment
The
highest
dose
tested
(1000
mg/
kg)
was
lethal.
A
major
limitation
of
this
study
was
the
number
of
animals
treated
and
the
number
of
cells
analyzed
per
animal.
At
most,
three
rats/
sex/
dose/
harvest
time
were
treated
with,
at
most,
50
cells
per
rat
analyzed.
Few
or
no
analyzable
cell
were
available
from
many
rats.
Positive
control
values
were
significantly
(p=
0.03)
increased.
There
was
no
evidence
that
H#
14,
14,555
induced
an
increase
in
the
incidence
of
chromosomal
aberrations
in
the
bone
marrow
cells
of
treated
animals.
17
This
study
is
classified
as
Unacceptable.
The
number
of
cells
analyzed
and
the
number
of
rats
treated
was
insufficient.
The
study
does
not
satisfy
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5385
(§
84
2)]
for
in
vivo
cytogenetic
mutagenicity
data.
Guideline
870.5550
Other
Genotoxic
Effects
Assay;
In
an
unscheduled
DNA
synthesis
assay
(MRID
00130708),
primary
rat
hepatocyte
cultures
were
exposed
to
INA
3674
112
(Lot
No.
7612
5E6E,
95%
a.
i.)
in
ethanol
for
18
hours
at
concentrations
of
1
x
10
5
,
1
x
10
4
,
1
x
10
3
,
1
x
10
2
,
0.1,
1.0,
10.0
and
30.0
mM
in
Trial
1
and
at
concentrations
of
1
x
10
5
,
1
x
10
4
,
1
x
10
3
,
1
x
10
2
,
0.1,
1.0,
5.0,
10.0
and
30.0
mM
in
Trial
2.
INA
3674
112
was
tested
up
to
the
highest
achievable
concentration
in
the
solvent.
Two
slides
per
dose,
25
cells
per
slide
were
evaluated
for
UDS
induction
in
Trial
1.
One
slide
per
dose,
25
cells
per
slide
were
evaluated
in
Trial
2.
The
author
did
not
report
that
the
slides
were
coded
prior
to
analysis.
The
average
net
nuclear
grain
counts
of
test
material
treated
cells
in
Trial
1
were
all
less
than
zero
with
the
exception
of
one
slide
at
1
x
10
5
mM
(0.1
±
9.6)
and
one
slide
at
1.0
mM
(1.6
±
5.2).
The
average
net
nuclear
grain
count
was
below
zero
for
all
test
material
concentrations
in
Trial
2
with
the
exception
of
0.1
mM
where
the
average
net
nuclear
grain
count
was
0.0
±
2.9.
The
criterion
for
a
positive
response
was
an
average
net
nuclear
grain
count
of
at
least
five
in
two
experiments
at
any
tested
concentration.
The
results
were
thus
negative.
The
number
of
cells
in
repair
was
not
reported.
The
solvent
and
positive
(DMBA)
controls
induced
the
appropriate
responses.
There
was
no
evidence
that
unscheduled
DNA
synthesis,
as
determined
by
radioactive
tracer
procedures
[nuclear
silver
grain
counts]
was
induced.
This
study
is
classified
as
Acceptable/
Guideline.
It
satisfies
the
requirement
for
FIFRA
Test
Guideline;
OPPTS
870.5550
[§
84
2]
for
other
genotoxic
mutagenicity
data.
5.
FQPA
CONSIDERATIONS
5.1
Adequacy
of
the
Data
Base
The
toxicity
data
base
for
FQPA
considerations
is
incomplete.
The
rabbit
developmental
toxicity
study
is
unacceptable/
upgradable
because
doses
were
not
analyzed
and
some
required
maternal
and
fetal
data
were
missing,
such
that
developmental
effects
seen
in
the
study
could
not
be
discounted
or
confirmed.
The
study
was
otherwise
acceptably
conducted.
Another
rabbit
developmental
toxicity
study
is
currently
in
progress.
A
rat
developmental
toxicity
study
is
acceptable
and
the
2
generation
reproduction
study
is
acceptable.
The
remaining
toxicity
data
base
is
adequate.
5.2
Neurotoxicity
Data:
No
neurotoxicity
studies
have
been
conducted.
The
chronic
dog
study
showed
a
statistically
18
significant
absolute
brain
weight
decrement
of
12
13%
in
the
female
dogs,
however,
these
dogs
showed
severe
malnutrition.
The
individual
animal
dog
data
showed
that
the
two
dogs
showing
the
largest
decreased
body
weight
from
the
initial
body
weight
also
showed
the
lowest
brain
weight.
This
severe
body
weight
decrement
in
females
may
have
resulted
in
nutritional
deficiencies
indirectly
affecting
the
brain
weight.
The
brain
weight
decrement
was
not
considered
to
be
a
direct
effect
of
hexazinone.
No
significant
changes
in
brain
weight
were
seen
in
the
rat
studies.
5.3
Developmental
Toxicity
5.3.1
Developmental
toxicity
in
rats
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
40397501),
hexazinone
(99.26%
a.
i.;
Lot#
S30306A,
Batch#
2/
36)
in
0.5%
methylcellulose
was
administered
orally
via
gavage
to
25
Crl:
CD
®
BR
female
rats/
group
at
dose
levels
of
0,
40,
100,
400,
or
900
mg/
kg
on
gestation
day
(GD)
7
through
16.
The
dosing
volume
was
10
mL/
kg
(calculated
by
reviewers).
All
dams
were
sacrificed
on
GD
22
and
their
fetuses
removed
by
cesarean
and
examined.
When
compared
to
concurrent
controls,
no
treatment
related
changes
in
clinical
signs,
gross
pathology,
pregnancy
rate,
live
fetuses,
resorptions,
pre
or
post
implantation
loss,
corpora
lutea,
or
implantations
were
noted
at
any
dose
level
tested.
No
treatment
related
findings
were
noted
in
the
100,
or
40
mg/
kg
groups.
In
the
900
mg/
kg
dams,
one
treatment
related
death
occurred;
alopecia
and
an
enlarged
stomach
containing
fluid
and
food
were
noted
at
necropsy.
Decreased
(p<
0.05)
body
weight
gains
were
noted
during
GDs
15
17
(937%)
and
17
22
(917%).
In
addition,
body
weight
gains
were
decreased
(p<
0.05)
for
the
overall
(GDs
7
17)
treatment
interval
(930%).
Gravid
uterine
weights
were
not
reported;
however,
adjusted
(for
gravid
uterine
weight)
terminal
body
weights
were
slightly
decreased
(96%;
p#0.05).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
GDs
9
11,
15
17,
7
17,
and
17
22.
Decreased
(p#0.05)
food
consumption
was
observed
throughout
treatment
(GDs
7
17;
916
22%)
and
post
treatment
(GDs
17
22;
99%).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
analysis
of
variance
(ANOVA)
was
noted
for
GDs
7
9,
9
11,
11
13,
13
15,
15
17,
7
17,
and
17
22.
Also
a
significantly
decreased
food
consumption
was
seen
at
400
mg/
kg/
day
(GD9
11;
91%)
and
(GD
7
17;
98%).
In
addition,
relative
(to
body)
liver
weights
were
increased
(p#0.05)
in
the
400
(5.2%)
and
900
(5.6%)
mg/
kg
dams
compared
to
concurrent
controls
(4.9%).
Decreased
(p#0.05)
terminal
body
weights
were
noted
at
900
mg/
kg
(96%).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
relative
liver
weights
and
adjusted
terminal
body
weights.
In
addition,
a
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
absolute
liver
weights.
Despite
this
trend,
the
observed
19
increases
in
absolute
liver
weights
at
100,
400,
and
900
mg/
kg
(81
8%)
were
not
statistically
significant.
Liver
weight
findings
are
considered
equivocal.
The
maternal
LOAEL
is
400
mg/
kg/
day
based
on
decreased
food
consumption
during
dosing
and
nominal
decreases
in
body
weight
gain
from
day
7
to
day
17
and
at
all
measured
intervals
between
and
at
900
mg/
kg/
day
on
mortality
and
decreased
body
weight
gains
and
food
consumption.
The
maternal
NOAEL
is
100
mg/
kg/
day.
In
the
900
mg/
kg/
day
group,
male
and
female
fetal
weights
were
decreased
(921%;
p#0.05);
a
significant
(p#0.05)
trend
by
Jonckheere's
test
was
noted
for
this
parameter.
At
400
mg/
kg/
day,
the
female
fetal
weights
that
were
significantly
decreased
were
not
considered
to
be
biologically
significant.
At
necropsy,
an
increased
(p#0.05)
incidence
of
misaligned
sternebra
(1),
a
variation,
was
observed
(fetal
incidence:
0.0217;
litter
incidence:
0.30)
relative
to
concurrent
controls
(fetal
incidence:
0.0066;
litter
incidence:
0.09).
In
addition,
an
increased
(p#0.05)
incidence
of
misaligned
sternebrae
(2+),
a
variation,
was
noted
(fetal
incidence:
0.0217;
litter
incidence:
0.30)
relative
to
concurrent
controls
(fetal
incidence:
0.0033;
litter
incidence:
0.04).
Furthermore,
an
increased
incidence
of
kidneys
with
no
papilla
was
observed
(fetal
incidence:
0.0347;
litter
incidence:
0.25)
relative
to
concurrent
controls
(fetal
incidence:
0.0062;
litter
incidence:
0.04).
Although
the
incidence
was
not
statistically
significant,
a
doserelated
trend
(p#0.05)
was
observed.
The
developmental
toxicity
LOAEL
is
900
mg/
kg/
day,
based
on
decreased
male
and
female
fetal
weight,
increased
incidence
of
kidneys
with
no
papilla
(malformation),
and
an
increased
incidence
of
misaligned
sternebrae
(variation).
The
developmental
toxicity
NOAEL
is
400
mg/
kg/
day.
The
developmental
toxicity
study
in
the
rat
is
classified
acceptable/
guideline
(OPPTS
870.3700;
§83
3
a)
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
in
the
rat.
An
unacceptable
developmental
feeding
study
in
the
rat
shows
(MRID#
00114486)
a
maternal
body
weight
decrement
at
482
mg/
kg/
day
with
a
NOAEL
of
94.5
mg/
kg/
day
with
a
developmental
NOAEL
of
482mg/
kg/
day.
This
study
tends
to
add
support
the
acceptable
rat
developmental
(by
gavage)
toxicity
study.
5.3.2
Developmental
Toxicity
in
the
rabbit
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
00028863),
hexazinone
(100%
a.
i.;
Lot/
batch
#
E21216A)
was
administered
orally
via
gavage
in
a
dosing
volume
of
1
mL/
kg)
to
17
female
New
Zealand
White
rabbits/
group
at
dose
levels
of
0,
20,
50,
or
125
mg/
kg
on
GD
6
through
19.
All
does
(except
those
that
died
or
delivered
prematurely)
were
sacrificed
on
GD
29,
and
their
fetuses
removed
by
cesarean
and
examined.
20
When
compared
to
concurrent
controls,
no
treatment
related
changes
in
mortality,
clinical
signs,
body
weights,
gross
pathology,
fetal
weights,
sex
ratios,
pre
implantation
or
postimplantation
losses,
or
the
number
of
corpora
lutea,
implantations,
resorptions,
live
fetuses,
or
dead
fetuses
were
observed.
At
125
mg/
kg,
food
consumption
was
decreased
(p#0.05),
relative
to
concurrent
controls,
at
the
beginning
of
treatment
from
GD
7
through
11
(961
89%).
Decreases
in
food
consumption,
that
were
not
statistically
significant,
continued
throughout
treatment
(GDs
12
19;
92
37%).
Diminished
food
consumption
resulted
in
decreased
(not
statistically
significant)
body
weight
gains
in
the
does
(
241.5
g)
relative
to
concurrent
controls
(
7.2
g)
during
GDs
6
11.
However,
weight
gain
in
these
animals
recovered
quickly
and
was
higher
than
control
animals
during
subsequent
treatment
intervals
(GDs
11
15
and
15
19).
The
maternal
LOAEL
is
125
mg/
kg/
day
based
on
transient
decreases
in
food
consumption
and
body
weight
gains.
The
maternal
NOAEL
is
50
mg/
kg/
day.
At
125
mg/
kg/
day,
the
following
skeletal
variations
were
noted
(data
presented
as
fetal
incidence
vs.
0
controls):
(i)
lagging
ossification
in
extremities
(0.0882);
(ii)
malaligned
thoracic
vertebrae
(0.0294);
and
(iii)
flexed
wrist(
s)
(0.0294).
In
addition,
non
ossified
thumb,
an
anomaly,
was
noted
at
an
increased
incidence
(0.0294)
relative
to
concurrent
controls
(0).
In
the
absence
of
historical
control
data,
these
findings
are
considered
treatment
related.
In
addition,
it
could
not
be
determined
how
many
of
these
nominally
increased
incidences
were
from
different
litters,
which
would
have
increased
concern
for
developmental
toxicity.
The
developmental
toxicity
LOAEL
is
125
mg/
kg/
day,
based
on
possible
skeletal
abnormalities
and
total
abnormalies.
The
developmental
toxicity
NOAEL
is
50
mg/
kg/
day.
The
developmental
toxicity
study
in
the
rabbit
is
classified
unacceptable/
upgradable,
pending
submission
of
acceptable
purity,
concentration,
stability
and
litter
data
and
historical
control
data.
A
letter
dated
9/
26/
01
from
the
registrant
provided
no
additional
information
about
this
rabbit
developmental
toxicity
study
other
than
that
the
doses
were
not
analyzed
and
that
a
repeat
rabbit
developmental
toxicity
was
currently
being
conducted.
5.4
Reproductive
Toxicity
5.4.1
Executive
Summary:
In
a
two
generation
reproduction
study,
hexazinone
(98%
a.
i.,
Lot
No.
T02118994)
was
administered
to
groups
of
30
male
and
30
female
Sprague
Dawley
rats
in
the
diet
at
concentrations
of
0,
200,
2000,
or
5000
ppm
(MRID
42066501).
One
litter
was
produced
in
the
first
generation
and
two
litters
were
produced
in
the
second
generation.
Test
substance
intake
for
the
treated
F0
groups
was
11.8,
117,
and
294
mg/
kg/
day,
respectively,
for
21
males
and
14.3,
143,
and
383
mg/
kg/
day,
respectively,
for
females.
Test
substance
intake
for
the
treated
F1
groups
was
15.3,
154,
and
399
mg/
kg/
day,
respectively,
for
males
and
17.7,
180,
and
484
mg/
kg/
day,
respectively,
for
females.
F0
and
F1
parental
animals
were
administered
test
or
control
diet
for
73
or
105
days,
respectively,
prior
to
mating,
throughout
mating,
gestation,
and
lactation,
and
until
necropsy.
Deaths
of
several
F0
and
F1
parental
animals
were
considered
incidental
to
treatment.
No
treatment
related
clinical
signs
of
toxicity
were
observed
in
the
adult
animals
of
either
generation.
Gross
necropsy
was
unremarkable
and
no
microscopic
lesions
were
observed
in
selected
tissues
from
the
reproductive
tracts
of
male
and
female
parental
animals.
Body
weights
and
body
weight
gains
of
the
F0
males
were
not
affected
by
treatment.
Premating
body
weight
gains
by
the
mid
and
high
dose
F0
females
were
76%
and
62%
(p
#
0.05
for
both),
respectively,
of
the
control
level
resulting
in
final
premating
body
weights
93%
and
87%
(p
#
0.05),
respectively,
of
the
controls.
Body
weights
of
the
high
dose
F1
males
and
females
were
significantly
reduced
(p
#
0.05)
during
the
premating
interval
with
overall
weight
gains
87%
and
82%,
respectively,
of
the
control
group
amounts.
Reductions
in
body
weights
and
body
weight
gains
during
premating
for
the
mid
and
high
dose
F0
and
high
dose
F1
dams
continued
during
gestation
and
lactation.
Food
consumption
during
premating
was
similar
between
the
treated
and
control
groups
for
males
and
females
of
both
generations.
However,
during
gestation
significantly
(p
#
0.05)
lower
food
consumption
was
noted
for
the
high
dose
F1
dams
during
production
of
both
litters
and
for
the
mid
dose
F1
dams
during
production
of
the
second
litter.
There
was
a
statistically
significant
increase
in
absolute
P0
testes
weight
that
appeared
to
be
dose
related,
but
a
nominally
decrease
absolute
F1
adult
testes
weight
in
the
5000
ppm
dose
groups.
The
F1
testes
weight
change
did
not
appear
to
dose
related.
The
testes
weight
changes
in
males
would
appear
to
be
incidental.
Therefore,
the
systemic
toxicity
LOAEL
is
2000
ppm
(117
154
mg/
kg/
day
for
males
and
143
180
mg/
kg/
day
for
females)
based
on
reduced
body
weight
and
body
weight
gains
by
F1
males
and
F0
and
F1
females.
The
systemic
toxicity
NOAEL
is
200
ppm
(11.8
15.3
mg/
kg/
day
for
males
and
14.3
17.7
mg/
kg/
day
for
females).
No
reproductive
effects
were
seen
in
the
study
except
for
the
weight
effects
on
offspring.
Live
birth
and
viability
indices
and
litter
survival
were
similar
between
the
treated
and
control
groups.
The
lactation
index
for
the
F2b
high
dose
litters
was
85.8%
(p
#
0.05)
compared
to
97.5%
for
the
control
group.
Pup
body
weights
were
decreased
throughout
lactation
in
the
mid
and
high
dose
groups
of
all
litters
as
compared
with
the
control
groups
with
statistical
significance
(p
#
0.05)
attained
at
most
time
points.
The
lower
pup
body
weights
were
more
pronounced
in
females
than
in
males.
F1
and
F2a
female
pup
weights
were
statistically
significantly
decreased
at
birth,
day
7
and
14
of
lactation
at
$2000
ppm.
There
were
no
obvious
reproductive
effects
other
than
the
pup
weight
decrement.
22
Therefore,
the
offspring
LOAEL
is
2000
ppm
(117
154
mg/
kg/
day
for
males
and
143
180
mg/
kg/
day
for
females)
based
on
reduced
female
pup
body
weights
at
birth
and
during
lactation.
The
reproductive
toxicity
NOAEL
was
200
ppm
(11.8
15.3
mg/
kg/
day
for
males
and
14.3
17.7
mg/
kg/
day
for
females).
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
guideline
requirements
for
a
reproductive
toxicity
study
[OPPTS
870.3800
(§
83
4)]
in
rats.
5.5
Additional
Information
from
Literature
Sources
(if
available)
The
published
literature
found
on
hexazinone
were
the
papers
on
the
same
studies
submitted
to
the
Agency
[
Kennedy,
GL
and
Kaplan,
AM
(1984)
Chronic
Toxicity,
Reproductive,
and
Teratogenic
Studies
of
Hexazinone.
Fundemental
and
applied
Toxicology
4,
960
971.].
No
other
relevant
literature
on
the
toxicity
was
found.
5.6
Determination
of
Susceptibility
No
quantitative
or
qualitative
evidence
of
increased
susceptibility
was
seen
following
in
utero
or
pre/
post
natal
exposure
to
rats.
The
rabbit
developmental
study
is
classified
as
unacceptable
because
of
technical
deficiencies.
On
April
2,
2002,
the
HIARC
concluded
that
susceptibility
in
this
species
could
not
be
assessed.
Since
the
unacceptable
study
indicates
that
a
lower
NOAEL/
LOAEL
may
be
demonstrated
in
the
rabbit,
the
committee
concluded
that
an
additional
database
uncertainty
factor
is
warranted
in
the
absence
of
this
study.
Additionally,
the
Committee
concluded
that
the
hazard
based
special
FQPA
safety
factor
is
1x
is
adequate
because
there
is
not
evidence
of
susceptibility
in
rats
and
a
database
uncertainty
factor
is
applied
to
the
acute
RfD
for
the
lack
of
a
rabbit
developmental
toxicity
study.
5.7
Determination
of
the
Need
for
Developmental
Neurotoxicity
Study
The
weight
of
evidence
does
not
suggest
the
need
for
a
Developmental
Neurotoxicity
study.
5.7.1
Evidence
that
suggest
requiring
a
Developmental
Neurotoxicity
study:
1.
The
structurally
related
pesticide,
Atrazine,
causes
CNS
related
changes
in
prolactin
secretion,
which
is
related
to
reproductive
senescence
in
Sprague
Dawley
rats
through
continuous
estrus
from
decreasing
LH
release,
but
this
effect
would
require
a
special
study
and
would
not
be
detected
by
a
neurotoxicity
study.
5.7.2
Evidence
that
do
not
support
the
need
for
a
Developmental
Neurotoxicity
study
1.
No
evidence
of
neurotoxicity
or
neuropathology
was
seen
in
the
database.
23
2.
A
12
13%
absolute
female
brain
decrement
was
seen
in
the
chronic
dog
study,
but
the
brain
weight
decrement
was
associated
with
severe
body
weight
decrement.
The
brain
weight
decrement
may
have
been
secondary
to
the
malnutrition
in
these
animals
and
not
directly
due
to
neurotoxic
effects
of
hexazinone
6.
HAZARD
CHARACTERIZATION
Hexazinone
is
a
herbicide
used
to
control
a
broad
spectrum
of
weeds
including
woody
plants
in
alfalfa,
rangeland,
pastures,
woodlands,
pineapple,
sugarcane
and
blue
berries.
Non
crop
areas
include
ornamental
plants
and
forests.
Hexazinone
is
used
as
a
pre
emergent,
post
emergence
herbicide
as
well
as
by
direct
spray
and
soil
applications.
There
are
no
non
occupational
(residential)
uses.
Hexazinone
has
low
acute
toxicity
by
the
oral
(Category
III),
dermal
(Category
IV
)
and
inhalation
routes
(Category
III).
Primary
eye
irritation
is
severe,
causing
corneal
opacity
and
moderate
irritation
in
unwashed
eyes
(Category
I).
It
causes
mild
skin
irritation
and
is
classified
Category
IV
for
skin
irritation.
It
is
not
a
skin
sensitizer
in
the
Guinea
pig.
Body
weight
decrement
and
liver
toxicity
were
the
most
frequent
effects
shown
in
studies
with
hexazinone.
Liver
toxicity
was
seen
in
the
chronic
dog
and
mouse
studies.
Body
weight
decrement
was
seen
in
the
chronic
rat
studies
and
the
studies
on
reproduction.
In
a
reproduction
study,
pup
weight
decrement
occurred
at
the
same
dose
as
parental
body
weight
decrement.
No
reproductive
effects
were
seen
in
the
study
other
than
pup
weight
decrement.
The
rat
prenatal
study
showed
fetal
weight
decrement
and
possibly
renal
malformations
but
no
increased
susceptibility.
The
rabbit
study
possibly
showed
skeletal
anomalies
and
delayed
ossifications
at
the
highest
dose
tested,
however
it
is
classified
as
unacceptable
and
susceptibility
in
this
species
could
not
be
assessed.
The
21
day
dermal
study
in
the
rabbit
showed
no
systemic
toxicity
and
mild
dermal
irritation
at
the
limit
dose.
The
chronic
study
in
dogs
showed
severe
body
weight
decrement,
changes
in
liver
related
clinical
chemistry
values,
and
microscopic
lesions.
Body
weight
decrement
was
seen
in
a
chronic
carcinogenicity
studies
in
rats
and
mice.
Liver
toxicity
was
seen
in
mice.
The
mouse
carcinogenicity
study
showed
an
increased
trend
for
liver
carcinomas,
but
no
pair
wise
significant
increases.
The
rat
study
showed
no
carcinogenic
potential.
Based
on
these
studies
in
rats
and
mice,
hexazinone
was
classified
in
a
group
D,
not
classifiable
as
a
carcinogen.
Rat
metabolism
studies
showed
that
hexazinone
was
rapidly
absorbed
and
excreted
and
essentially
no
difference
in
the
metabolism
of
males
and
females
at
high
or
low
dose
levels.
Almost
no
parent
hexazinone
was
recovered
in
urine
or
feces.
Two
major
metabolites
were
recovered
from
feces
and
urine,
in
addition
to
lesser
amounts
of
a
third
metabolite
and
small
amounts
conjugated
products
from
urine.
24
7.
Data
Gaps
The
HIARC
requested
a
28
day
inhalation
study
with
hexazinone
because
of
the
concern
for
potential
inhalation
exposure
based
on
the
use
pattern..
The
rabbit
developmental
toxicity
study
is
classified
as
unacceptable.
Another
study
in
the
rabbit,
requested
by
Cal
EPA,
is
expected
to
be
submitted
to
OPP
as
well.
8.
ACUTE
TOXICITY
Acute
Toxicity
of
Hexazinone
Guideline
No.
Study
Type
MRIDs
#
Results
Toxicity
Category
81
1
Acute
Oral/
Rat
41235004
(1989)
LD50
=
1200
mg/
kg
III
81
2
Acute
Dermal/
Rabbit
00104974
LD50
>5278
mg/
kg
IV
81
3
Acute
Inhalation
00104975
(1973)
LC50
>
7.50
mg/
L(
1
hour)
LC50
>1.9
mg/
L
1
Equivalent
to
340
mg/
kg
2
III
81
4
Primary
Eye
Irritation
00106003
(1982)
Irreversible
corneal
opacity,
Severe
3
I
81
5
Primary
Skin
Irritation
00106004
(1982)
Mild
IV
81
6
Dermal
Sensitization
41235005
(1989)
NA
Not
a
skin
sensitizer
81
8
Acute
Neurotoxicity
Not
conducted
1
One
hour
inhalation
study
on
technical
converted
to
probable
no
effects
at
4
hours.
Consistent
with
an
unreviewed
three
week
inhalation
study
(MRID#
00063972)
showing
no
significant
toxic
effects.
The
effects
seen
were
consistent
with
dust
inhalation
at
2.5
mg/
mL,
the
only
dose
tested.
Another
acute
4
hour
inhalation
study
in
rats
showed
no
effects
at
3.9
mg/
L
using
a
25%
a.
i.
granular
product
(MRID#
41756701).
2
Calculated
by
the
reviewer
from
the
following
information
from
Whalan
(1998).
This
conversion
generally
is
not
considered
valid,
especially
for
irritating
substances.
{[(
1.9
mg/
L
x
1
x
9.13
x
4
x
1)/(
0.204
kg)]
=
340
mg/
kg}
3
The
toxicity
category
was
based
on
the
corneal
opacity.
Irritation
not
counting
opacity
was
tox
category
III.
25
9.
SUMMARY
OF
TOXICOLOGY
ENDPOINT
SELECTION
Summary
of
Toxicology
Endpoint
Selection
for
Hexazinone
Exposure
Scenario
Dose
(mg/
kg/
day)
UF
/MOE
Hazard
Based
Special
FQPA
Safety
Factor
Endpoint
for
Risk
Assessment
Dietary
Risk
Assessments
Acute
Dietary
females
13
50
years
of
age
NOAEL
=
400
UF
=
100
Acute
RfD
=
0.40
mg/
kg/
day
UFdb
=
10
Developmental
Toxicity
Rat
Decreased
male
and
female
fetal
weight,
kidneys
with
no
papilla
(malformation)
and
misaligned
sternebrae
(variation)
Acute
Dietary
general
population
including
infants
and
children
An
appropriate
endpoint
attributable
to
a
single
dose
was
not
identified
in
the
oral
studies,
including
the
rat
and
rabbit
developmental
studies.
Chronic
Dietary
all
populations
NOAEL=
5.0
UF
=
100
Chronic
RfD
=
0.05
mg/
kg/
day
N/
A
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Incidental
Oral
Short
Term
(1
30
Days)
Residential
Only
There
are
no
residential
uses
at
the
present
time
and
therefore,
endpoints
were
not
selected.
Incidental
Oral
Intermediate
Term
(1
6
Months)
Residential
Only
There
are
no
residential
uses
at
the
present
time
and
therefore,
endpoints
were
not
selected.
Non
Dietary
Risk
Assessments
Dermal
Short
Term
(1
30
days)
No
hazard
was
identified,
therefore
quantification
of
risk
is
not
required.
No
systemic
toxicity
was
seen
at
the
limit
dose
following
repeat
dermal
application,
and
there
were
no
concerns
for
developmental
or
reproductive
toxicity.
Residential
Occupational
Exposure
Scenario
Dose
(mg/
kg/
day)
UF
/MOE
Hazard
Based
Special
FQPA
Safety
Factor
Endpoint
for
Risk
Assessment
26
Dermal
Intermediate
Term
1
(1
6
Months)
Oral
NOAEL=
5.0
mg/
kg/
day
N/
A
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Residential
N/
A
Occupational
MOE=
100
Dermal
Long
Term
1
(1
6
Months)
Oral
NOAEL=
5.0
mg/
kg/
day
N/
A
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Residential
N/
A
Occupational
MOE=
100
Inhalation
Short
Term
2
(1
30
days)
Oral
NOAEL=
100
mg/
kg/
day
Developmental
Toxicity
Rat
LOAEL=
400
mg/
kg/
day
based
on
decreases
in
maternal
food
consumption
and
dose
related
body
weight
decrement.
Residential
N/
A
Occupational
MOE=
100
Inhalation
Intermediate
Term
(1
6
Months)
Oral
NOAEL=
5.0
mg/
kg/
day
N/
A
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Residential
N/
A
Occupational
MOE=
100
Inhalation
Long
Term
(>
6
Months)
Oral
NOAEL=
5.0
mg/
kg/
day
N/
A
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Residential
N/
A
Occupational
MOE=
100
Cancer
Classification:
D
Not
Classifiable
as
to
human
carcinogenicity
1
Since
an
oral
NOAEL
was
selected
25%
dermal
absorption
factor
should
be
used
for
route
to
route
exposures.
27
2
Since
an
oral
NOAEL
was
selected
100%
inhalation
absorption
factor
should
be
used
for
route
to
route
exposures.
| epa | 2024-06-07T20:31:42.882273 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0013/content.txt"
} |
EPA-HQ-OPP-2002-0188-0014 | Supporting & Related Material | "2002-09-16T04:00:00" | null | TXR#
DATE:
1/
16/
02
MEMORANDUM
SUBJECT:
Hexazinone
Report
of
the
Hazard
Identification
Assessment
Review
Committee.
FROM:
David
G
Anderson
Toxicologist.
Reregistration
Branch
2
Health
Effects
Division
(7509C)
THROUGH:
Jess
Rowland,
Co
Chair
and
Elizabeth
Doyle,
Co
Chair
Hazard
Identification
Assessment
Review
Committee
Health
Effects
Division
(7509C)
TO:
Diana
Locke,
Risk
Assessor
Reregistration
Branch
2
Health
Effects
Division
(7509C)
PC
Code:
107201
On
Dec
4,
2001,
the
Health
Effects
Division
(HED)
Hazard
Identification
Assessment
Review
Committee
(HIARC)
reviewed
the
recommendations
of
the
toxicology
reviewer
for
HEXAZINONE
with
regard
to
the
acute
and
chronic
Reference
Doses
(RfDs)
and
the
toxicological
endpoint
selection
for
use
as
appropriate
in
occupational/
residential
exposure
risk
assessments.
The
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
HEXAZINONE
was
also
evaluated
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996.
The
conclusions
drawn
at
this
meeting
are
presented
in
this
report.
2
Committee
Members
in
Attendance
Members
present
were:
LIST
NAMES
Member(
s)
in
absentia:
LIST
NAMES
Data
evaluation
prepared
by:
TOXICOLOGIST,
BRANCH
Also
in
attendance
were:
LIST
NAMES
and
DIVISION
Data
Evaluation/
Report
presentation
David
G
Anderson
Toxicologist
3
1.
INTRODUCTION
On
December
4,
2001,
the
Health
Effects
Division
(HED)
Hazard
Identification
Assessment
Review
Committee
(HIARC)
reviewed
the
recommendations
of
the
toxicology
reviewer
for
HEXAZINONE
with
regard
to
the
acute
and
chronic
Reference
Doses
(RfDs)
and
the
toxicological
endpoint
selection
for
use
as
appropriate
in
occupational/
residential
exposure
risk
assessments.
The
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
HEXAZINONE
was
also
evaluated
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996.
The
last
review
of
the
hexazinone
toxicity
data
base
was
February
11,
1993,
by
the
RfD/
Peer
Review
Committee.
A
Reregistration
Eligibility
Document
was
issued
September,
1994
(EPA
738
F
94
019).
2.
HAZARD
IDENTIFICATION
2.1
Acute
Reference
Dose
(RfD)(
Population
Subgroup:
Females
13
50)
Study
Selected:
Developmental
toxicity
Study
in
Rats
§
870.3700
MRID
No.:
40397501
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
40397501),
hexazinone
(99.26%
a.
i.;
Lot#
S30306A,
Batch#
2/
36)
in
0.5%
methylcellulose
was
administered
orally
via
gavage
to
25
Crl:
CD
®
BR
female
rats/
group
at
dose
levels
of
0,
40,
100,
400,
or
900
mg/
kg
on
gestation
day
(GD)
7
through
16.
The
dosing
volume
was
10
mL/
kg
(calculated
by
reviewers).
All
dams
were
sacrificed
on
GD
22
and
their
fetuses
removed
by
cesarean
and
examined.
When
compared
to
concurrent
controls,
no
treatment
related
changes
in
clinical
signs,
gross
pathology,
pregnancy
rate,
live
fetuses,
resorptions,
pre
or
post
implantation
loss,
corpora
lutea,
or
implantations
were
noted
at
any
dose
level
tested.
No
treatment
related
findings
were
noted
in
the
100,
or
40
mg/
kg
groups.
In
the
900
mg/
kg
dams,
one
treatment
related
death
occurred;
alopecia
and
an
enlarged
stomach
containing
fluid
and
food
were
noted
at
necropsy.
Decreased
(p<
0.05)
body
weight
gains
were
noted
during
GDs
15
17
(937%)
and
17
22
(917%).
In
addition,
body
weight
gains
were
decreased
(p<
0.05)
for
the
overall
(GDs
7
17)
treatment
interval
(930%).
Gravid
uterine
weights
were
not
reported;
however,
adjusted
(for
gravid
uterine
weight)
terminal
body
weights
were
slightly
decreased
(96%;
p#0.05).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
GDs
9
11,
15
17,
7
17,
and
17
22.
Decreased
(p#0.05)
food
consumption
was
observed
throughout
treatment
(GDs
7
17;
916
22%)
and
post
treatment
(GDs
17
22;
99%).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
GDs
7
9,
9
11,
11
13,
13
15,
15
17,
7
17,
and
17
22.
Also
a
significantly
decreased
food
consumption
was
seen
at
400
mg/
kg/
day
(GD9
11;
91%)
and
(GD
7
17;
98%).
In
addition,
relative
(to
body)
liver
weights
were
increased
(p#0.05)
in
the
400
(5.2%)
and
900
(5.6%)
mg/
kg
dams
compared
to
concurrent
controls
(4.9%).
Decreased
(p#0.05)
terminal
body
weights
were
noted
at
900
mg/
kg
(96%).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
4
ANOVA
was
noted
for
relative
liver
weights
and
adjusted
terminal
body
weights.
In
addition,
a
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
absolute
liver
weights.
Despite
this
trend,
the
observed
increases
in
absolute
liver
weights
at
100,
400,
and
900
mg/
kg
(81
8%)
were
not
statistically
significant.
Liver
weight
findings
are
considered
equivocal.
The
maternal
LOAEL
is
400
mg/
kg/
day
based
on
decreased
food
consumption
during
dosing
and
nominal
decreases
in
body
weight
gain
from
day
7
to
day
17
and
at
all
measured
intervals
between
and
at
900
mg/
kg/
day
on
mortality
and
decreased
body
weight
gains
and
food
consumption.
The
maternal
NOAEL
is
100
mg/
kg/
day.
In
the
900
mg/
kg/
day
group,
male
and
female
fetal
weights
were
decreased
(921%;
p#0.05);
a
significant
(p#0.05)
trend
by
Jonckheere's
test
was
noted
for
this
parameter.
At
400
mg/
kg/
day,
only
female
fetal
weights
were
significantly
decreased
(2%)
but
were
not
considered
to
biologically
significantly
depressed.
At
900
mg/
kg/
day,
an
increased
(p#0.05)
incidence
of
misaligned
sternebra
(1),
a
variation,
was
observed
(fetal
incidence:
0.0217;
litter
incidence:
0.30)
relative
to
concurrent
controls
(fetal
incidence:
0.0066;
litter
incidence:
0.09).
In
addition,
an
increased
(p#0.05)
incidence
of
misaligned
sternebrae
(2+),
a
variation,
was
noted
(fetal
incidence:
0.0217;
litter
incidence:
0.30)
relative
to
concurrent
controls
(fetal
incidence:
0.0033;
litter
incidence:
0.04).
Furthermore,
an
increased
incidence
of
kidneys
with
no
papilla
was
observed
(fetal
incidence:
0.0347;
litter
incidence:
0.25)
relative
to
concurrent
controls
(fetal
incidence:
0.0062;
litter
incidence:
0.04).
Although
the
incidence
was
not
statistically
significant,
a
dose
related
trend
(p#0.05)
was
observed.
The
developmental
toxicity
LOAEL
is
900
mg/
kg/
day,
based
on
decreased
male
and
female
fetal
weight
and
increased
incidence
of
kidneys
with
no
papilla
(malformation),
and
an
increased
incidence
of
misaligned
sternebrae
(variation).
The
developmental
toxicity
NOAEL
is
400
mg/
kg/
day.
The
developmental
toxicity
study
in
the
rat
is
classified
acceptable/
guideline
(OPPTS
870.3700;
§83
3
a)
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
in
the
rat.
Dose
and
Endpoint
for
Establishing
RfD:
Developmental
NOAEL
is
400
mg/
kg/
day.
The
LOAEL
is
900
mg/
kg/
day
based
on
increased
kidneys
with
no
papillae
and
misaligned
sternebrae.
Uncertainty
Factor
(UF):
100
Comments
about
Study/
Endpoint/
Uncertainty
Factor:
The
malformations
(kidneys
with
no
papillae)
are
presumed
to
occur
after
a
single
and
thus
appropriate
for
acute
risk
assessment.
The
rabbit
developmental
toxicity
study
showed
a
lower
NOAEL
of
50
mg/
kg/
day
and
LOAEL
of
125
mg/
kg/
day
based
possible
skeletal
and
total
abnormalities.
The
HIARC
did
not
select
this
study
because
of
uncertainties
in
the
effects
at
the
LOAEL.
The
technical
accuracy
and
overall
confidence
in
this
study
was
low
and
the
study
is
classified
unacceptable.
Acute
RfD(
Females
13
50)
=
400
mg/
kg
=
4.0
mg/
kg
100
(UF)
5
2.2
Acute
Reference
Dose
(RfD)(
General
Population)
An
appropriate
endpoint
attributable
to
a
single
dose
was
not
identified
in
the
oral
studies,
including
the
rat
and
rabbit
developmental
studies.
2.3
Chronic
Reference
Dose
(RfD)
Study
Selected:
One
Year
Chronic
Dog
Study
Guideline
#:
870.4100
MRID
No.:
42162301
Executive
Summary:
In
a
one
year
chronic
toxicity
study,
hexazinone
(98%
a.
i.,
Lot
No.
T02118994)
was
administered
to
groups
of
5
male
and
5
female
beagle
dogs
in
the
diet
at
concentrations
of
0,
200,
1500,
or
6000
ppm
(MRID
42162301).
Time
weighted
average
doses
for
the
treated
groups
were
5.00,
41.24,
and
161.48
mg/
kg/
day,
respectively,
for
males
and
4.97,
37.57,
and
166.99
mg/
kg/
day,
respectively,
for
females.
All
animals
survived
to
scheduled
necropsy.
Treatment
related
clinical
signs
of
toxicity
included
the
observation
of
thinness
in
1/
5
mid
dose
males,
3/
5
high
dose
males,
and
1/
5
high
dose
females.
Body
weights
of
the
high
dose
groups
were
significantly
(p
#
0.05)
less
than
those
of
the
control
throughout
most
of
the
study.
Final
body
weights
of
the
high
dose
males
and
females
were
78%
and
67%,
respectively,
of
the
control
levels.
Food
consumption
by
the
high
dose
groups
was
slightly
(n.
s.)
less
than
that
of
the
controls
throughout
the
study
with
statistical
significance
(p
#
0.05)
attained
for
females
at
week
52.
Overall
food
consumption
(weeks
1
52)
for
high
dose
males
and
females
was
85%
(n.
s.)
and
74%
(p
#
0.05),
respectively,
of
the
control
group
levels.
Body
weights
and
food
consumption
for
the
low
and
mid
dose
groups
were
not
affected
by
treatment.
No
treatment
related
ophthalmological
lesions,
changes
in
urinalysis
parameters,
or
gross
necropsy
findings
were
noted.
A
moderate
macrocytic
anemia
was
observed
in
the
high
dose
groups
as
evidenced
by
slight
or
significant
(p
#
0.05)
decreases
in
RBC
counts,
hemoglobin,
and
hematocrit
and
increases
in
MCV
and
MCH
in
one
or
both
sexes
throughout
the
study.
Cholesterol
levels
were
significantly
(p
#
0.05)
decreased
in
the
high
dose
groups
beginning
at
week
13
for
males
(52
64%
of
controls)
and
at
week
26
for
females
(45
51%
of
controls).
Albumin
levels
were
significantly
(p
#
0.05)
decreased
in
the
mid
dose
males
(93%
of
controls)
at
week
13
only,
and
in
the
highdose
males
(74
78%
of
controls)
and
females
(75
82%
of
controls)
throughout
the
study.
Beginning
on
week
13
or
26,
the
high
dose
groups
had
aspartate
aminotransferase
levels
140
203%
(p
#
0.05)
of
the
control
values
and
alanine
aminotransferase
levels
206
276%
(p
#
0.05)
of
the
control
values.
Alkaline
phosphatase
levels
were
significantly
(p
#
0.05)
increased
in
the
mid
dose
males
(259
409%
of
controls)
and
females
(163
194%
of
controls;
n.
s.)
beginning
at
week
26
and
in
the
high
dose
males
(346
1363%
of
controls)
and
females
(307
559%
of
controls)
beginning
at
week
13.
For
the
high
dose
animals,
decreases
in
absolute
testes
weights
in
males
and
kidney,
heart,
and
brain
weights
in
females
(
12%)
and
increases
in
relative
liver
weights
in
males
and
females
were
considered
due
to
lower
final
body
weights
of
these
animals
as
compared
with
controls.
6
Microscopic
lesions
in
the
liver
of
high
dose
animals
included
concentric
membranous
bodies
in
4
males
and
5
females,
centrilobular
single
cell
necrosis
in
3
males
and
3
females,
hepatocellular
pigment
in
3
males
and
3
females,
and
vacuolation
in
3
males
and
4
females.
In
addition
vacuolation
was
observed
in
one
mid
dose
male
and
pigment
and
membranous
bodies
were
each
observed
in
one
mid
dose
female.
These
lesions
were
not
seen
in
control
or
low
dose
animals.
Therefore,
the
LOAEL
for
hexazinone
in
male
and
female
beagle
dogs
is
1500
ppm
(41.24
and
37.57
mg/
kg/
day,
respectively)
based
on
thinness
in
one
male
and
hepatotoxicity
as
evidenced
by
changes
in
clinical
chemistry
parameters
and
microscopic
lesions.
The
NOAEL
is
200
ppm
(5.00
and
4.97
mg/
kg/
day,
respectively).
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
guideline
requirements
for
a
chronic
toxicity
study
[OPPTS
870.4100
(§
83
1b)]
in
dogs.
Proposed
Dose
and
Endpoint
for
Establishing
RfD:
NOAEL
of
5.0
mg/
kg/
day.
The
LOAEL
is
38
mg/
kg/
day
based
on
elevated
clinical
chemistry
values
(serum
alkaline
phosphatase,
serum
aspartate
aminotransferase),
other
changes
in
clinical
chemistry
values,
liver
microscopic
findings
and
body
weight
decrement
and
clinical
observation
of
thinnest
in
one
male
(4
of
10
males
and
females
at
the
next
higher
dose).
Proposed
Uncertainty
Factor(
s):
100
Comments
about
Study/
Endpoint/
Uncertainty
Factor(
s):
The
study
is
of
the
appropriate
duration.
The
RfD/
peer
Review
Committee
chose
the
same
value
in
1994,
which
formed
the
basis
of
the
Chronic
RfD
for
the
1994
RED.
2.4
Occupational/
Residential
Exposure
2.4.1
Short
Term
(1
Day
1
Month)
and
Intermediate
Term
(1
Month
6
Months)
Incidental
Oral
Exposure
Toxicity
endpoints
for
incidental
oral
exposure
were
not
selected
since
there
are
no
residential
exposure
based
on
the
current
use
pattern
and
none
is
anticipated
in
the
future.
2.4.2
Dermal
Absorption
No
dermal
absorption
study
is
available.
For
dermal
absorption,
the
NOAEL
from
the
21
day
Chronic
RfD
=
5.0
mg/
kg/
day
(NOAEL)
=
0.05
mg/
kg/
day
100
(UF)
7
dermal
toxicity
study
at
the
limit
dose
of
1000
mg/
kg/
day
was
considered
a
lower
bound
for
the
LOAEL,
which
was
compared
with
LOAEL
of
250
mg/
kg/
day
from
the
range
finding
rabbit
study
(MRID#
00028863).
The
ratio
of
these
two
numbers
was
used
to
estimate
a
dermal
absorption
factor
of
25%.
The
range
finding
study
was
chosen
instead
of
the
main
rabbit
developmental
toxicity
study
(MRID#
00028863)
for
comparison
because
the
main
study
was
considered
to
be
unacceptable
for
regulatory
purposes.
Dermal
Absorption
Factor:
25%
Comments
about
Study/
Endpoint:
The
use
of
a
25%
dermal
absorption
factor
for
route
to
route
extrapolation
of
oral
studies
to
occupational
dermal
exposure
would
be
protective
of
the
developmental
effects
seen
in
the
rat
study.
2.4.3
Short
Term
Dermal
(1
Day
1
Month)
Exposure
Study
Selected:
None
§
MRID
No.:
None
Executive
Summary:
None
Dose
and
Endpoint
for
Risk
Assessment:
Not
applicable
Comments
about
Study/
Endpoint:
No
hazard
and
no
quantification
required.
There
were
no
systemic
effects
at
1000
mg/
kg/
day,
limit
dose,
in
the
21
day
dermal
study
in
rabbits
(MRID#
41309005).
The
oral
developmental
NOAEL
(400
mg/
kg/
day)
in
conjunction
with
the
use
of
25%
dermal
absorption
factor
yields
a
dermal
equivalent
dose
of
1600
mg/
kg/
day
[(
400/
0.25)=
1600
mg/
kg/
day],
which
is
higher
than
the
limit
dose
in
the
rabbit
21
day
dermal
study
and
will
adequately
protect
pesticide
handlers
from
developmental
toxicity.
2.4.4
Intermediate
Term
Dermal
(1
6
Months)
and
Long
Term
Dermal
(longer
than
6
Months)
Exposure
Study
Selected:
Chronic
Feeding
Study
in
Dogs
§
870.4100
MRID
No.:
42162301
Executive
Summary:
[See
Section
2.3
on
the
Chronic
Reference
Dose
(RfD).]
8
Dose/
Endpoint
for
Risk
Assessment:
NOAEL
is
5.0
mg/
kg/
day.
The
LOAEL
is
38
mg/
kg/
day
based
on
elevated
clinical
chemistry
values
(serum
alkaline
phosphatase,
serum
aspartate
aminotransferase),
other
changes
in
clinical
chemistry
values,
liver
microscopic
findings
and
body
weight
decrement
and
the
clinical
observation
of
thinnest
in
one
male.
Comments
about
Study/
Endpoint:
The
elevation
in
clinical
chemistry
parameters
were
seen
at
3
and
6
months
and
thus
appropriate
fro
the
exposure
period.
Since
an
oral
NOAEL
was
selected,
a
25%
dermal
absorption
factor
should
be
used
for
route
to
route
exposure.
2.4.5
Short
Term
Inhalation
Exposure
(1
day
to
1
Month)
Study
Selected:
Developmental
Toxicity
in
the
Rat
§
870.3700
MRID
No.:
40397501
Executive
Summary:
[See
Section
2.1
Acute
Reference
Dose
(RfD).]
Dose/
Endpoint
for
Risk
Assessment:
The
maternal
NOAEL
is
100
mg/
kg/
day.
The
LOAEL
is
400
mg/
kg/
day
based
on
based
on
maternal
body
weight
and
food
consumption
decrement.
Comments
about
Study/
Endpoint:
In
the
absence
of
a
inhalation
study,
the
maternal
NOAEL
was
selected.
The
dosing
period
was
appropriate
for
this
exposure
and
is
protective
of
developmental
effects.
For
the
route
to
route
exposures
assume
100%
absorption.
2.4.6
Intermediate
Term
inhalation
(1
Month
to
6
Months)
and
Long
Term
Inhalation
(longer
than
6
Months)
Exposure.
Study
Selected:
Chronic
Feeding
Study
in
Dogs
§
870.4100
MRID
No.:
42162301
Executive
Summary:
[See
Section
2.3
on
the
Chronic
Reference
Dose
(RfD).]
Dose/
Endpoint
for
Risk
Assessment:
NOAEL
is
5.0
mg/
kg/
day.
The
LOAEL
is
38
mg/
kg/
day
based
on
elevated
clinical
chemistry
values
(serum
alkaline
phosphatase,
serum
aspartate
aminotransferase),
other
changes
in
clinical
chemistry
values,
liver
microscopic
findings
and
body
weight
decrement
and
clinical
observation
of
thinnest
in
one
male
(4
of
10
males
and
females
at
the
next
higher
dose).
9
Comments
about
Study/
Endpoint:
The
affects
seen
in
clinical
chemistry
values
at
3,
6
and
12
months
are
appropriate
for
these
exposure
periods.
Assume
100%
absorption
in
route
to
route
assessment.
2.5
Margins
of
Exposure
for
Occupational/
Residential
Risk
Assessment
A
margin
of
exposure
of
100
is
adequate
for
occupational
dermal
and
inhalation
exposure.
There
is
no
non
occupational
(residential)
exposures
identified
at
this
time.
2.6
Recommendation
for
Aggregate
Exposure
Risk
Assessments
Aggregate
exposure
risk
assessment
is
not
required
since
there
are
no
non
occupational
(residential)
uses
at
the
present
time.
3.
CLASSIFICATION
OF
CARCINOGENIC
POTENTIAL
3.1
Combined
Chronic
Toxicity/
Carcinogenicity
Study
in
Rats
MRID
No.
00108638
Executive
Summary:
In
this
combined
chronic/
oncogenicity
study
(MRID
00108638),
hexazinone
(94
96%
a.
i.;
Lot/
Batch
#:
6897
40
and
74.25)
was
administered
in
the
diet
to
ChR
CD
rats
(36/
sex/
group)
for
up
to
25
months
at
nominal
doses
of
0,
0,
200,
1000,
or
2500
ppm
(equivalent
to
0,
0,
10.2,
53.4,
and
138.3
mg/
kg/
day
in
males
and
0,
0,
12.5,
67.5,
and
178.6
mg/
kg/
day
in
females).
No
treatment
related
differences
were
observed
in
mortality,
clinical
signs,
food
consumption,
hematology,
clinical
chemistry,
organ
weights,
and
gross
or
microscopic
pathology.
No
adverse
effects
were
observed
in
the
200
ppm
animals.
There
were
several
signs
of
general
toxicity,
but
a
target
organ
could
not
be
clearly
identified
at
any
dose.
Terminal
body
weights
were
decreased
8%
in1000
ppm
and
20%,
p#0.05,
in
the
2500
ppm
females.
A
decrease
in
overall
body
weight
gain
(Days
0
728;
calculated
by
the
reviewers)
was
also
observed
in
the
1000
(
10%)
and
2500
ppm
(
25%)
females.
Nominal
decreases
in
body
weight
and
body
weight
gain
(
3
to
5%)
occurred
in
males
at
1000
ppm
during
the
study,
which
may
have
been
biologically
significant
at
the
end
of
the
study
(
12%
body
weight
and
14%
for
body
weight
gain).
Decreases
(p
values
not
calculated)
in
total
food
efficiency
were
observed
in
females
at
1000
(
10%)
and
2500
ppm
(
25%)
and
in
males
at
1000
ppm
during
the
study
with
overall
decrement
in
food
efficiency
in
1000
ppm
males
(
10%).
In
males
at
2500
ppm,
food
efficiency
was
depressed
for
the
first
6
months
of
the
study
25
but
from
6
months
to
the
end
of
the
study,
it
was
increased
139%.
The
reviewer
noted
problems
interpreting
the
body
weights
and
food
efficiency
in
males
at
the
top
dose
level,
which
were
not
consistent
with
the
mid
dose
level.
For
the
first
6
months
of
the
study
in
males,
a
body
10
weight
decrement
due
to
probable
toxicity
was
seen
at
1000
and
2500
ppm.
After
6
months
food
efficiency
in
males
at
the
1000
ppm
remained
less
than
controls
(
56%)
while
food
efficiency
at
2500
ppm
in
males
was
higher
than
controls
(+
139%)(
Table
4).
By
the
end
of
the
study,
male
body
weight
at
1000
ppm
was
12%
and
body
weight
gain
14%,
where
as
body
weight
and
body
weight
gain
in
males
at
2500
ppm
was
+3%
for
both
weight
and
gain.
The
reason
for
this
recovery
in
male
body
weight
decrement
at
2500
ppm
is
unknown,
but
it
appears
to
be
real.
[Since
absolute
and
relative
liver
weights
were
decreased
in
males
at
2500
ppm,
liver
enzyme
induction
allowing
the
recovery
seems
unproven.]
The
body
weight
decrement
at
1000
and
2500
ppm
with
recovery
in
body
weight
at
2500
ppm
indicates
the
an
adequate
dose
level
to
test
for
carcinogenicity
in
males
was
approached,
but
probably
not
attained.
Other
treatment
groups
were
similar
to
the
average
of
concurrent
controls.
Dosing
was
considered
adequate
based
on
decreased
body
weights,
body
weight
gains,
and
food
efficiency
in
the
2500
and
1000
ppm
females
and
food
efficiency
and
body
weights
in
the
2500
ppm
males
for
the
first
6
months.
Body
weight
(
12%)
and
body
weight
gain
(
14%)
in
males
at
1000
ppm
were
decreased
at
the
end
of
the
study,
in
addition
overall
food
efficiency
(
14%)
was
decreased
by
the
end
of
the
study.
Thus
female
body
weight
and
body
weight
gain
was
decreased
sufficiently
to
adequately
test
for
carcinogenicity.
Male
body
weight
and
body
weight
gain
at1000
ppm
appeared
to
be
adequate
to
test
for
carcinogenicity
by
the
end
of
the
study,
but
the
lack
of
dose
response
in
male
body
weight
and
body
weight
gain
at
2500
ppm
(showing
recovery
after
6
months
such
that
body
weight
and
body
weight
gain
were
higher
than
control
values)
may
indicate
problems
with
the
interpretation
of
the
body
weights
and
body
weight
gains
at
1000
ppm.
In
the
2500
ppm
males,
creatinine
was
increased
(NS)
in
the
urine
at
months
18
and
24
and
bilirubin
was
detected
at
month
18
and
24.
The
Sponsor
reported
that
the
urine
was
more
alkaline
in
the
2500
ppm
treatment
groups
(data
not
reported).
Also
at
2500
ppm,
decreased
(p#0.05)
absolute
and
relative
liver
and
kidney
organ
weights
were
observed
in
the
males
and
increased
(p#0.05)
relative
(to
body)
stomach
and
kidney
organ
weights
were
observed
in
the
females.
However,
histopathological
data
did
not
corroborate
these
findings.
The
LOAEL
is
1000
ppm
for
males
and
females
(equivalent
to
53.3
for
males
and
67.5
mg/
kg/
day
for
females)
based
on
decreased
body
weight
and
food
efficiency
in
males
and
females.
In
males
at
2500
ppm
the
body
weight
decrement
and
food
efficiency
decrement
occurred
only
for
the
first
6
months
of
the
study.
The
NOAEL
is
200
ppm
for
males
and
females
(10.2
for
males
and
12.5
mg/
kg/
day
for
females).
Neoplasm
data
were
evaluated
by
two
pathologists.
An
increase
incidence
of
thyroid
C
cell
adenomas
was
observed
in
the
2500
ppm
males,
but
when
analyzed
by
the
Fisher's
exact
test
(p>
0.10)
or
life
table
methods
(p>
0.20)
no
significant
differences
were
observed
between
controls
and
treated
groups.
Using
life
table
analyses
a
significant
(p<
0.05)
dose
response
trend
was
observed
in
thyroid
C
cell
tumors
in
only
one
of
the
two
pathology
reports.
Female
rats
did
not
show
any
potential
for
C
cell
thyroid
adenomas.
The
incidence,
malignancy
and
latency
of
tumors
were
comparable
among
control
and
treated
rats
of
both
sexes.
Under
the
conditions
of
this
study,
carcinogenic
potential
of
hexazinone
is
considered
negative.
The
submitted
study
is
classified
as
acceptable
for
guideline
870.4300
combined
11
chronic/
carcinogenicity
study
in
rats.
Discussion
of
Tumor
Data:
Neoplasm
data
were
evaluated
by
two
pathologists.
An
increase
incidence
of
thyroid
C
cell
adenomas
was
observed
in
the
2500
ppm
males,
but
when
analyzed
by
the
Fisher's
exact
test
(p>
0.10)
or
life
table
methods
(p>
0.20)
no
significant
differences
were
observed
between
controls
and
treated
groups.
Using
life
table
analyses
a
significant
(p<
0.05)
dose
response
trend
was
observed
in
thyroid
C
cell
tumors
in
only
one
of
the
two
pathology
reports.
Female
rats
did
not
show
any
potential
for
C
cell
thyroid
adenomas.
The
incidence,
malignancy
and
latency
of
tumors
were
comparable
among
control
and
treated
rats
of
both
sexes.
The
study
in
rats
does
not
support
a
carcinogenic
potential
for
hexazinone.
Adequacy
of
the
Dose
Levels
Tested:
The
dose
levels
in
female
rats
was
adequate
to
test
for
the
carcinogenic
potential
hexazinone.
There
was
an
adequate
body
weight
decrement
and
body
weight
gain
decrement
at
the
two
top
dose
levels.
The
dose
levels
in
male
rats
approached
an
adequate
dose
level
to
test
for
carcinogenic
potential
of
hexazinone.
There
may
have
been
an
adequate
body
weight
and
body
weight
gain
at
the
mid
dose
level
at
the
end
of
the
study
to
test
for
carcinogenic
potential
of
hexazinone,
however
body
weights
of
males
at
the
top
dose
level
behaved
atypically.
At
the
top
dose
level,
males
showed
a
adequate
body
weight
decrement
only
for
the
first
6
months
of
the
study
and
by
the
end
of
the
study,
body
weights
were
higher
than
the
average
of
the
two
controls.
The
reason
for
this
reversible
body
weight
decrement
is
unknown,
but
the
top
dose
level
in
males
was
one
half
the
top
dose
level
of
5000
ppm
in
the
90
day
subchronic
study
in
males
where
liver
toxicity
was
seen.
These
body
weight
decrements
in
males
and
females
are
supported
by
a
corresponding
decrements
in
food
efficiency.
3.2
Carcinogenicity
Study
in
Mice
MRID
No.
41359301,42509301
and
43202901
§
870.4200
Executive
Summary:
In
this
mouse
oncogenicity
study
(MRIDs
00079203,
41359301,
42509301
and
43202901),
hexazinone
($95%
a.
i.;
Lot/
Batch
#:
H
11,
265
and
265
2)
was
administered
in
the
diet
to
CD
1
mice
(80/
sex/
group)
for
up
to
104
weeks
at
nominal
doses
of
0,
200,
2500
or
10,000
ppm
(equivalent
to
28,
366
and
1635
mg/
kg/
day
in
males
and
0,
34,
450
and
1915
mg/
kg/
day
in
females).
No
treatment
related
differences
were
observed
in
mortality,
food
consumption,
food
efficiency
or
hematology.
Hepatotoxicity
was
evident
at
the
terminal
sacrifice.
Macroscopic
liver
nodule/
mass
(%
treated
vs
%
controls;
n
=
28
55)
was
observed
in
males
at
2500
(39%
vs
7%)
and
10,000
ppm
(33%).
Increased
incidences
(%
treated
vs
0%
controls;
n
=
38
55)
in
the
following
microscopic
liver
lesions
were
observed:
hyperplastic
nodule(
s)
(includes
both
foci
of
cellular
alteration
and
adenoma)
in
males
at
2500
(39%
vs
20%)
and
10,000
ppm
(36%)
and
in
females
at
10,000
ppm
(15%
vs
3%);
and
necrosis
(severity
and
type
12
unspecified)
in
the
10,000
ppm
males
(36%
vs
7%).
Centrilobular
hepatocyte
hypertrophy
was
observed
(%
treated
vs
%
controls)
at
the
terminal
sacrifice
(n
=
38
55)
in
males
at
2500
(18%
vs
0%)
and
10,000
ppm
(98%)
and
in
females
at
10,000
ppm
(46%
vs
0%)
and
in
the
dead
and
moribund
males
(n
=
25
40)
at
2500
(44%
vs
0%)
and
10,000
ppm
(60%).
Increased
(p#0.05
or
0.01)
liver/
gall
bladder
weights
were
observed
at
10,000
ppm
in
males
in
both
absolute
and
relative
to
body
weights
and
in
females
in
relative
to
body
weight.
Other
signs
of
toxicity
were
evident.
Distal
tail
tip
sloughing
and/
or
discoloration
was
observed
at
10,000
ppm
in
males
at
Weeks
13
104
and
in
females
at
Weeks
5
and
13
104.
Macroscopically,
tip
of
tail
missing/
sloughed
was
observed
at
the
terminal
sacrifice
in
the
10,000
ppm
males
(31%
vs
5%)
and
females
(61%
vs
11%)
and
in
the
dead
and
moribund
10,000
ppm
females
(46%
vs
2%).
The
toxicological
significance
of
these
findings
was
unclear.
Minor
decreases
(p#0.05
or
0.01)
in
body
weights
were
observed
in
the
10,000
ppm
treatment
groups
at
Weeks
13
104
in
both
sexes.
Overall
body
weight
gains
(calculated
by
the
reviewers)
were
decreased
in
the
10,000
ppm
males
(925%)
and
females
(931%).
The
LOAEL
is
2500
ppm
for
males
(equivalent
to
366
mg/
kg/
day)
based
on
gross
liver
nodules/
masses,
hyperplastic
nodules
in
the
liver
and
centrilobular
hepatocyte
hypertrophy
and
10,000
ppm
for
females
(equivalent
to
1915
mg/
kg/
day
[limit
dose])
based
on
decreased
body
weights,
increased
relative
liver/
gall
bladder
weights,
hyperplastic
nodules
and
centrilobular
hepatocyte
hypertrophy.
The
NOAEL
is
200
ppm
(equivalent
to
28
mg/
kg/
day)
for
males
and
2500
ppm
(equivalent
to
450
mg/
kg/
day)
for
females.
Liver
samples
were
first
evaluated
using
the
term
hyperplastic
nodule
which
did
not
clearly
distinguish
neoplasia
from
non
neoplasia.
Reevaluation
was
conducted
to
make
this
distinction,
and
no
significant
differences
were
observed
between
the
treatment
groups
and
the
concurrent
controls.
However
positive
trends
(p<
0.05)
were
observed
(%
treated
vs
%
controls)
in
focus/
foci
of
cellular
alteration
in
males,
hepatocellular
neoplasm(
s)
(including
adenoma,
sarcoma,
carcinoma,
leukemia,
and
lymphoma)
in
females,
and
singular
hepatocellular
adenoma
in
females.
Focus/
foci
of
cellular
alteration
were
observed
in
males
at
2500
(11.3%
vs
5.0%)
and
10,000
ppm
(24.1%)
and
females
at
10,000
ppm
(12.5%
vs
3.8%)
beginning
at
Week
57.
Singular
hepatocellular
adenoma
was
observed
in
the
10,000
ppm
females
(7.5%
vs
2.5%)
beginning
at
Week
77.
Hepatocellular
neoplasm(
s)
were
observed
in
the
10,000
ppm
females
(8.8%
vs
2.5%).
A
carcinoma
in
the
10,000
ppm
treatment
groups
was
first
observed
at
Week
65.
The
incidence
of
carcinomas
were
within
historical
control
ranges
for
each
sex,
while
the
incidence
of
adenomas
were
increased
by
3.21%
in
the
10,000
ppm
females.
A
dose
dependent
increase
in
adenomas
was
not
observed
in
males.
The
Health
Effects
Division
Carcinogenicity
Peer
Review
Committee
(CPRC)
concluded
that
hexazinone
should
be
classified
as
a
Group
D
(not
classifiable
as
to
human
carcinogenicity)(
7/
27/
94).
Under
the
conditions
of
this
study,
evidence
of
carcinogenic
potential
was
equivocal:
a
positive
trend
test
for
neoplasia
was
observed
in
female
mice,
but
no
significant
difference
was
determined
by
pair
wise
comparison.
The
submitted
study
is
classified
as
acceptable
for
guideline
870
4200
carcinogenicity
study
in
mice.
Discussion
of
Tumor
Data:
A
dose
dependent
increase
in
adenomas
was
not
observed
in
males.
The
Health
Effects
Division
Carcinogenicity
Peer
Review
Committee
(CPRC)
concluded
that
hexazinone
should
be
classified
as
a
Group
D
(not
classifiable
as
to
human
carcinogenicity)(
7/
27/
94).
13
Under
the
conditions
of
this
study,
evidence
of
carcinogenic
potential
was
equivocal:
a
positive
trend
test
for
neoplasia
was
observed
in
female
mice,
but
no
significant
difference
was
determined
by
pairwise
comparison.
Adequacy
of
the
Dose
Levels
Tested:
Adequate
dose
levels
were
used
in
male
and
female
mice
to
test
for
the
carcinogenic
potential
of
hexazinone.
Liver
toxicity
was
seen
at
the
top
dose
level
in
males
and
females.
3.3
Classification
of
Carcinogenic
Potential
The
Health
Effects
Division
Carcinogenicity
Peer
Review
Committee
(CPRC)
concluded
that
hexazinone
should
be
classified
as
a
Group
D
(not
classifiable
as
to
human
carcinogenicity)(
7/
27/
94).
In
rats,
females
showed
no
evidence
of
carcinogenic
potential
and
males
showed
a
significant
trend
only
in
thyroid
adenomas.
In
mice,
the
evidence
of
carcinogenic
potential
was
equivocal:
a
positive
trend
test
for
neoplasia
was
observed
in
female
mice,
but
no
significant
difference
was
seen
by
pair
wise
comparison.
The
top
doses
in
rats
and
mice
were
adequate
to
test
for
carcinogenicity.
4.
MUTAGENICITY
The
required
mutagenicity
testing
is
complete.
This
section
was
copied
from
the
1994
RED
for
Hexazinone
and
the
updated
DERs.
One
mutagenicity
study
was
submitted
since
the
1994
RED
was
written;
a
negative
in
vivo
mammalian
micronucleus
test
in
mouse
bone
marrow
cells
(MRID#
45124401).
Hexazinone
was
found
to
be
positive
for
mutagenicity
in
one
chromosomal
aberration
assay
(in
vitro
cytogenics)
(MRID#
00130709),
but
negative
in
the
remaining
studies.
It
is
concluded
that
the
test
material
was
clastogenic
in
both
of
the
nonactivated
trials
and
was
also
clastogenic
in
the
one
adequate
S9
activated
trials.
Under
both
test
conditions,
concentrations
providing
evidence
of
clastogenicity
induced
an
acceptable
level
of
cytotoxicity
(>
50%
relative
cell
survival).
Thus,
the
findings
can
not
be
considered
to
be
a
secondary
effect
of
cytotoxicity.
Nevertheless,
the
outcome
of
the
induced
structural
damage
(i.
e.,
primarily
chromatid
and
chromosome
breaks)
is
unclear
since
these
types
of
structural
aberrations
would
not
likely
be
passed
on
to
daughter
cells.
Because
unambiguous
positive
results
were
achieved,
it
was
concluded
that
the
study
provided
adequate
evidence
that
INA
3674
112
(hexazinone,
technical)
is
clastogenic
in
an
acceptable
study.
4.1
Guideline
870.5100
Gene
Mutation
Assay
in
Ames
Test:
Hexazinone
was
tested
with
metabolic
activation
(rat
liver
microsomal
fraction
commonly
known
as
S
9
fraction,
plus
cofactors)
at
concentrations
ranging
from
400
to
2000
ug/
plate
and
without
metabolic
activation
14
at
concentrations
ranging
from
200
to
1000
ug/
plate.
The
strains
of
Salmonella
typhimurium
used
were
TA1535,
TA1537,
TA1538,
TA98
and
TA100.
No
increases
in
reverse
mutations
were
observed
at
any
concentration.
Positive
results
were
obtained
with
standard
reference
mutagens
(positive
controls)(
MRID
00098982).
4.2
Guideline
870.5100
Reverse
mutation
assay:
In
a
reverse
gene
mutation
assay
in
bacteria
(MRID
40826201),
strains
TA98,
TA100,
TA1535,
TA1537
and
TA1538
of
S.
typhimurium
were
exposed
to
S
triazine
2,4(
1H,
3H)
dione,
3
cyclohexyl
6
dimethylamino1
methyl
(95%
a.
i.)
in
ethanol
at
concentrations
of
200,
400,
600,
800
and
1000
:g/
plate
without
mammalian
metabolic
activation
(S9
mix)
and
at
concentrations
of
400,
800,
1200,
1600
and
2000
:g/
mL
with
S9
mix.
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
male
Crl:
CD(
SD)
BR
rat
liver.
The
maximum
concentrations
of
S
triazine
2,4(
1H,
3H)
dione,
3
cyclohexyl
6
dimethylamino
1
methyl
tested
produced
little
or
no
cytotoxicity,
were
not
limited
by
solubility
and
were
not
a
limit
dose
for
the
assay.
No
statistically
significant
increases
in
the
number
of
revertants
per
plate
or
positive
linear
dose
response
were
seen.
The
solvent
and
positive
controls
induced
acceptable
responses
in
the
corresponding
strains.
There
was
no
evidence
of
induced
mutant
colonies
over
background.
This
study
is
classified
as
Unacceptable.
It
does
not
satisfy
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5100
(§
84
2)]
for
in
vitro
mutagenicity
[bacterial
reverse
gene
mutation]
data
and
should
be
repeated
using
higher
doses.
4.3
Guideline
870.5300:
Gene
Mutation
Assay
in
Mammalian
Cells:
In
a
mammalian
cell
gene
mutation
assay
at
the
HGPRT
locus
(MRID
No.
00076956),
Chinese
hamster
CHO
K1
BH4
cells
cultured
in
vitro
were
exposed
to
INA
3674
112,
(Lot
No.
7612
5E6E,
95%
a.
i.)
in
ethanol
in
two
trials.
Concentrations
used
in
Trial
1
were
2.0,
11.1,
13.1,
13.9
and
14.3
mM
under
nonactivated
conditions
and
concentrations
of
2.0,
7.9,
8.9,
9.3
and
9.9
mM
under
activated
conditions
(S9
mix).
Concentrations
used
in
Trial
2
were
2.0,
5.9,
11.1,
13.1
and
13.9
mM
without
S9
mix
and
concentrations
of
2.0,
7.9,
8.9,
9.3
and
9.9
mM
with
S9
mix.
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
male
Charles
River
CD®
rat
livers.
INA
3674
112
was
tested
up
to
cytotoxic
concentrations.
In
Trial
1,
the
cultures
treated
at
14.3
mM
S9
were
not
plated
for
mutation
determination
due
to
cytotoxicity
in
both
Trials
1
and
2.
Cytotoxicity
was
also
noted
at
9.9
mM
+S9.
No
statistically
significant
increases
in
mutant
frequency
over
solvent
control
values
were
seen
with
or
without
S9
mix
in
either
Trial
1
or
2.
The
expected
marked
increase
in
the
mutation
were
seen
with
the
positive
controls.
There
was,
however,
no
indication
that
INA
3674
112
induced
a
mutagenic
effect
either
in
the
presence
or
the
absence
of
S9
activation.
This
study
is
classified
as
acceptable.
It
satisfies
the
requirement
for
FIFRA
Test
Guideline
OPPTS
[870.5300
(§
84
2)]
for
in
vitro
mutagenicity
(mammalian
forward
gene
mutation)
data.
15
4.4
Guideline:
870.5395
Mouse
bone
marrow
micronucleus
assay:
In
a
Crl:
CD
1
(ICR)
BR
mouse
bone
marrow
micronucleus
assay
(MRID
45124401),
5
mice/
sex/
dose/
harvest
time
were
treated
orally
with
Hexazinone
25L
(Lot
No.
9912033,
25%
Hexazinone
a.
i.
(24.5%
by
analysis)
and
75%
inert
ingredients)
at
doses
of
1000,
2000
and
3000
mg/
kg.
Bone
marrow
cells
were
harvested
at
24
and
48
hours
post
treatment
and
examined
for
micronucleated
polychromatic
erythrocytes
(MPCEs).
The
vehicle
was
Milli
Q
®
water.
Signs
of
toxicity
noted
at
3000
mg/
kg
included:
death,
convulsions,
half
shut
eyes,
head
tilt,
irregular
respiration,
lethargy,
low
carriage,
pallor,
prostration,
uncontrollable
spinning,
shovel
nosing,
straining
up
on
toes
and
tremors.
Micronuclei
were
scored
in
bone
marrow
from
mice
treated
at
3000
mg/
kg
and
from
the
solvent
and
positive
controls.
Mice
from
the
two
lower
dose
groups
were
not
evaluated
for
micronuclei
induction.
No
statistically
significant
increases
in
the
frequency
of
MPCEs
or
in
the
PCE/
NCE
ratio
over
the
solvent
control
values
were
seen
in
either
sex
at
either
the
24
or
48
hour
harvest
time.
The
solvent
and
positive
control
values
were
appropriate
and
within
the
testing
laboratory's
historical
control
ranges.
There
was
no
evidence
that
Hexazinone
25L
induced
a
clastogenic
or
aneugenic
effect
in
bone
marrow
at
any
harvest
time.
This
study
is
classified
as
Acceptable/
Guideline.
It
satisfy
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5395
(§
84
2)]
for
in
vivo
cytogenetic
mutagenicity
data.
4.5
Guideline
870.5375
Structural
Chromosome
Aberration
Assay;
In
vitro
Cytogenetic
Assay:
In
a
mammalian
cell
cytogenetics
assay
(MRID
No.
00130709),
Chinese
hamster
ovary
CHO
K1
BH4
cell
cultures
were
exposed
to
INA
3674
112
(Hexazinone,
95%
a.
i.)
in
ethanol
in
two
separate
trials.
Exposure
was
for
two
hours
with
activation
and
for
10
hours
without
activation.
Cells
were
harvested
10
hours
after
the
start
of
treatment.
In
Trial
1,
cells
were
treated
at
concentrations
of
1.58,
3.94,
15.85
and
19.82
mM
without
metabolic
activation
(S9
mix)
and
at
concentrations
of
0.32,
3.17,
7.93
and
15.85
mM
with
S9
mix.
In
Trial
2,
cells
were
treated
at
concentrations
of
1.58,
3.94,
7.93
and
15.85
without
S9
mix
and
at
concentrations
of
0.32,
3.17,
7.93
and
15.85
mM
with
S9
mix.
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
CD
rat
livers.
INA
3674
112
was
tested
up
to
cytotoxic
concentrations.
Based
on
the
results
of
a
preliminary
cytotoxicity
test,
upper
concentrations
of
23.78
mM
without
S9
mix
and
47.56
mM
with
S9
mix
were
selected
for
the
first
cytogenetic
assay
but
these
concentrations
proved
excessively
cytotoxic
and
were
not
scored
for
chromosomal
aberrations.
Without
S9
activation,
statistically
significant
increases
(p<
0.01)
in
structural
aberrations
per
cell
(excluding
gaps),
lesions
per
cell
and
percent
abnormal
cells
were
seen
at
15.85
mM
(Trials
1
and
2)
and
19.82
mM
(tested
in
Trial
1
only).
Relative
percent
survival
(RPS)
at
this
level
was
.50%.
The
percent
abnormal
cells
averaged
over
all
cultures
from
both
trials
was
28.0%
and
21.5%
at
19.82
and
15.85
mM,
respectively,
compared
to
the
solvent
control
values
of
2.0%
(0.5%
ethanol
in
Trial
2)
and
7.0%
(0.75%
ethanol
in
Trial
1).
The
percent
abnormal
cells
in
positive
control
cultures
was
18%
in
both
Trial
1
(4.83
mM
EMS)
and
Trial
2
(6.44
mM
EMS).
In
the
presence
of
S9
mix,
no
statistically
significant
increases
in
chromosomal
aberration
induction
16
were
seen
in
Trial
1;
however,
very
low
positive
control
values
indicated
a
problem
with
the
S9
mix.
Statistically
significant
increases
were
seen
at
15.85
mM
in
Trial
2;
RPS
at
15.85
mM
was
75%.
There
was
a
statistically
significant
dose
related
trend
for
all
three
parameters.
The
statistically
significant
(p
<0.01)
increases
at
15.85
mM
remained
when
the
data
from
Trial
1
and
2
were
combined
(average
of
20%
abnormal
cells
compared
to
10%
for
the
solvent
control).
The
predominant
aberrations
with
or
without
S9
mix
were
chromatid
and
isochromatid
breaks.
Solvent
and
positive
controls
(except
the
positive
control
in
Trial
1
with
S9
mix)
induced
the
appropriate
responses.
INA
3674
112
was
positive
for
the
induction
of
structural
chromosomal
aberrations
in
both
the
presence
and
absence
of
S9
mix.
This
study
is
classified
as
Acceptable/
guideline
and
satisfies
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5375
(§
84
2)]
for
in
vitro
cytogenetic
mutagenicity
data.
4.6
Guideline
870.5385
Structural
Chromosome
Aberration
Assay;
In
vivo
Cytogenetic
Assay:
In
a
mammalian
cell
cytogenetics
assay
(MRID
00131355),
in
bone
marrow
cells
of
Sprague
Dawley
CD
rats,
three
rats/
dose/
sex/
harvest
time
were
exposed
to
H#
14,555
in
corn
oil
(
assumed
100%
a.
i.)
at
doses
of
100,
300
and
1000
mg/
kg
by
oral
gavage.
Bone
marrow
cells
were
harvested
at
6,
12,
24
and
48
hours
post
treatment.
The
highest
dose
tested
(1000
mg/
kg)
was
lethal.
A
major
limitation
of
this
study
was
the
number
of
animals
treated
and
the
number
of
cells
analyzed
per
animal.
At
most,
three
rats/
sex/
dose/
harvest
time
were
treated
with,
at
most,
50
cells
per
rat
analyzed.
Few
or
no
analyzable
cell
were
available
from
many
rats.
Positive
control
values
were
significantly
(p=
0.03)
increased.
There
was
no
evidence
that
H#
14,
14,555
induced
an
increase
in
the
incidence
of
chromosomal
aberrations
in
the
bone
marrow
cells
of
treated
animals.
This
study
is
classified
as
Unacceptable.
The
number
of
cells
analyzed
and
the
number
of
rats
treated
was
insufficient.
The
study
does
not
satisfy
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5385
(§
84
2)]
for
in
vivo
cytogenetic
mutagenicity
data.
4.7
Guideline
870.5550
Other
Genotoxic
Effects
Assay;
In
an
unscheduled
DNA
synthesis
assay
(MRID
00130708),
primary
rat
hepatocyte
cultures
were
exposed
to
INA
3674
112
(Lot
No.
7612
5E6E,
95%
a.
i.)
in
ethanol
for
18
hours
at
concentrations
of
1
x
10
5
,
1
x
10
4
,
1
x
10
3
,
1
x
10
2
,
0.1,
1.0,
10.0
and
30.0
mM
in
Trial
1
and
at
concentrations
of
1
x
10
5
,
1
x
10
4
,
1
x
10
3
,
1
x
10
2
,
0.1,
1.0,
5.0,
10.0
and
30.0
mM
in
Trial
2.
INA
3674
112
was
tested
up
to
the
highest
achievable
concentration
in
the
solvent.
Two
slides
per
dose,
25
cells
per
slide
were
evaluated
for
UDS
induction
in
Trial
1.
One
slide
per
dose,
25
cells
per
slide
were
evaluated
in
Trial
2.
The
author
did
not
report
that
the
slides
were
coded
prior
to
analysis.
The
average
net
nuclear
grain
counts
of
test
material
treated
cells
in
Trial
1
were
all
less
than
zero
with
the
exception
of
one
slide
at
1
x
10
5
mM
(0.1
±
9.6)
and
one
slide
at
1.0
mM
(1.6
±
5.2).
The
average
net
nuclear
grain
count
was
below
zero
for
all
test
material
concentrations
in
Trial
2
with
the
exception
of
0.1
mM
where
the
average
net
nuclear
grain
count
was
0.0
±
2.9.
The
criterion
for
a
positive
response
was
an
average
net
nuclear
grain
count
of
at
least
five
in
two
experiments
at
any
tested
concentration.
The
results
17
were
thus
negative.
The
number
of
cells
in
repair
was
not
reported.
The
solvent
and
positive
(DMBA)
controls
induced
the
appropriate
responses.
There
was
no
evidence
that
unscheduled
DNA
synthesis,
as
determined
by
radioactive
tracer
procedures
[nuclear
silver
grain
counts]
was
induced.
This
study
is
classified
as
Acceptable/
Guideline.
It
satisfies
the
requirement
for
FIFRA
Test
Guideline;
OPPTS
870.5550
[§
84
2]
for
other
genotoxic
mutagenicity
data.
5.
FQPA
CONSIDERATIONS
5.1
Adequacy
of
the
Data
Base
The
toxicity
data
base
for
FQPA
considerations
is
incomplete.
The
rabbit
developmental
toxicity
study
is
unacceptable/
upgradable
because
doses
were
not
analyzed
and
some
required
maternal
and
fetal
data
were
missing,
such
that
developmental
effects
seen
in
the
study
could
not
be
discounted
or
confirmed.
The
study
was
otherwise
acceptably
conducted.
Another
rabbit
developmental
toxicity
study
is
currently
in
progress.
A
rat
developmental
toxicity
study
is
acceptable
and
the
2
generation
reproduction
study
is
acceptable.
The
remaining
toxicity
data
base
is
adequate.
5.2
Neurotoxicity
Data:
No
neurotoxicity
studies
have
been
conducted.
The
chronic
dog
study
showed
a
statistically
significant
absolute
brain
weight
decrement
of
12
13%
in
the
female
dogs,
however,
these
dogs
showed
severe
malnutrition.
The
individual
animal
dog
data
showed
that
the
two
dogs
showing
the
largest
decreased
body
weight
from
the
initial
body
weight
also
showed
the
lowest
brain
weight.
This
severe
body
weight
decrement
in
females
may
have
resulted
in
nutritional
deficiencies
indirectly
affecting
the
brain
weight.
The
brain
weight
decrement
was
not
considered
to
be
a
direct
effect
of
hexazinone.
No
significant
changes
in
brain
weight
were
seen
in
the
rat
studies.
5.3
Developmental
Toxicity
5.3.1
Developmental
toxicity
in
rats
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
40397501),
hexazinone
(99.26%
a.
i.;
Lot#
S30306A,
Batch#
2/
36)
in
0.5%
methylcellulose
was
administered
orally
via
gavage
to
25
Crl:
CD
®
BR
female
rats/
group
at
dose
levels
of
0,
40,
100,
400,
or
900
mg/
kg
on
gestation
day
(GD)
7
through
16.
The
dosing
volume
was
10
mL/
kg
(calculated
by
reviewers).
All
dams
were
sacrificed
on
GD
22
and
their
fetuses
removed
by
cesarean
and
examined.
When
compared
to
concurrent
controls,
no
treatment
related
changes
in
clinical
signs,
gross
pathology,
pregnancy
rate,
live
fetuses,
resorptions,
pre
or
post
implantation
loss,
corpora
lutea,
or
implantations
were
18
noted
at
any
dose
level
tested.
No
treatment
related
findings
were
noted
in
the
100,
or
40
mg/
kg
groups.
In
the
900
mg/
kg
dams,
one
treatment
related
death
occurred;
alopecia
and
an
enlarged
stomach
containing
fluid
and
food
were
noted
at
necropsy.
Decreased
(p<
0.05)
body
weight
gains
were
noted
during
GDs
15
17
(937%)
and
17
22
(917%).
In
addition,
body
weight
gains
were
decreased
(p<
0.05)
for
the
overall
(GDs
7
17)
treatment
interval
(930%).
Gravid
uterine
weights
were
not
reported;
however,
adjusted
(for
gravid
uterine
weight)
terminal
body
weights
were
slightly
decreased
(96%;
p#0.05).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
GDs
9
11,
15
17,
7
17,
and
17
22.
Decreased
(p#0.05)
food
consumption
was
observed
throughout
treatment
(GDs
7
17;
916
22%)
and
post
treatment
(GDs
17
22;
99%).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
analysis
of
variance
(ANOVA)
was
noted
for
GDs
7
9,
9
11,
11
13,
13
15,
15
17,
7
17,
and
17
22.
Also
a
significantly
decreased
food
consumption
was
seen
at
400
mg/
kg/
day
(GD9
11;
91%)
and
(GD
7
17;
98%).
In
addition,
relative
(to
body)
liver
weights
were
increased
(p#0.05)
in
the
400
(5.2%)
and
900
(5.6%)
mg/
kg
dams
compared
to
concurrent
controls
(4.9%).
Decreased
(p#0.05)
terminal
body
weights
were
noted
at
900
mg/
kg
(96%).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
relative
liver
weights
and
adjusted
terminal
body
weights.
In
addition,
a
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
absolute
liver
weights.
Despite
this
trend,
the
observed
increases
in
absolute
liver
weights
at
100,
400,
and
900
mg/
kg
(81
8%)
were
not
statistically
significant.
Liver
weight
findings
are
considered
equivocal.
The
maternal
LOAEL
is
400
mg/
kg/
day
based
on
decreased
food
consumption
during
dosing
and
nominal
decreases
in
body
weight
gain
from
day
7
to
day
17
and
at
all
measured
intervals
between
and
at
900
mg/
kg/
day
on
mortality
and
decreased
body
weight
gains
and
food
consumption.
The
maternal
NOAEL
is
100
mg/
kg/
day.
In
the
900
mg/
kg/
day
group,
male
and
female
fetal
weights
were
decreased
(921%;
p#0.05);
a
significant
(p#0.05)
trend
by
Jonckheere's
test
was
noted
for
this
parameter.
At
400
mg/
kg/
day,
the
female
fetal
weights
that
were
significantly
decreased
were
not
considered
to
be
biologically
significant.
At
necropsy,
an
increased
(p#0.05)
incidence
of
misaligned
sternebra
(1),
a
variation,
was
observed
(fetal
incidence:
0.0217;
litter
incidence:
0.30)
relative
to
concurrent
controls
(fetal
incidence:
0.0066;
litter
incidence:
0.09).
In
addition,
an
increased
(p#0.05)
incidence
of
misaligned
sternebrae
(2+),
a
variation,
was
noted
(fetal
incidence:
0.0217;
litter
incidence:
0.30)
relative
to
concurrent
controls
(fetal
incidence:
0.0033;
litter
incidence:
0.04).
Furthermore,
an
increased
incidence
of
kidneys
with
no
papilla
was
observed
(fetal
incidence:
0.0347;
litter
incidence:
0.25)
relative
to
concurrent
controls
(fetal
incidence:
0.0062;
litter
incidence:
0.04).
Although
the
incidence
was
not
statistically
significant,
a
dose
related
trend
(p#0.05)
was
observed.
The
developmental
toxicity
LOAEL
is
900
mg/
kg/
day,
based
on
decreased
male
and
female
fetal
weight,
increased
incidence
of
kidneys
with
no
papilla
(malformation),
and
an
increased
incidence
of
misaligned
sternebrae
(variation).
The
developmental
toxicity
NOAEL
is
400
mg/
kg/
day.
The
developmental
toxicity
study
in
the
rat
is
classified
acceptable/
guideline
(OPPTS
870.3700;
§83
3
a)
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
in
the
rat.
An
unacceptable
developmental
feeding
study
in
the
rat
shows
(MRID#
00114486)
a
maternal
body
weight
decrement
at
482
mg/
kg/
day
with
a
NOAEL
of
94.5
mg/
kg/
day
with
a
developmental
NOAEL
of
19
482mg/
kg/
day.
This
study
tends
to
add
support
the
acceptable
rat
developmental
(by
gavage)
toxicity
study.
5.3.2
Developmental
Toxicity
in
the
rabbit
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
00028863),
hexazinone
(100%
a.
i.;
Lot/
batch
#
E21216A)
was
administered
orally
via
gavage
in
a
dosing
volume
of
1
mL/
kg)
to
17
female
New
Zealand
White
rabbits/
group
at
dose
levels
of
0,
20,
50,
or
125
mg/
kg
on
GD
6
through
19.
All
does
(except
those
that
died
or
delivered
prematurely)
were
sacrificed
on
GD
29,
and
their
fetuses
removed
by
cesarean
and
examined.
When
compared
to
concurrent
controls,
no
treatment
related
changes
in
mortality,
clinical
signs,
body
weights,
gross
pathology,
fetal
weights,
sex
ratios,
pre
implantation
or
post
implantation
losses,
or
the
number
of
corpora
lutea,
implantations,
resorptions,
live
fetuses,
or
dead
fetuses
were
observed.
At
125
mg/
kg,
food
consumption
was
decreased
(p#0.05),
relative
to
concurrent
controls,
at
the
beginning
of
treatment
from
GD
7
through
11
(961
89%).
Decreases
in
food
consumption,
that
were
not
statistically
significant,
continued
throughout
treatment
(GDs
12
19;
92
37%).
Diminished
food
consumption
resulted
in
decreased
(not
statistically
significant)
body
weight
gains
in
the
does
(
241.5
g)
relative
to
concurrent
controls
(
7.2
g)
during
GDs
6
11.
However,
weight
gain
in
these
animals
recovered
quickly
and
was
higher
than
control
animals
during
subsequent
treatment
intervals
(GDs
11
15
and
15
19).
The
maternal
LOAEL
is
125
mg/
kg/
day
based
on
transient
decreases
in
food
consumption
and
body
weight
gains.
The
maternal
NOAEL
is
50
mg/
kg/
day.
At
125
mg/
kg/
day,
the
following
skeletal
variations
were
noted
(data
presented
as
fetal
incidence
vs.
0
controls):
(i)
lagging
ossification
in
extremities
(0.0882);
(ii)
malaligned
thoracic
vertebrae
(0.0294);
and
(iii)
flexed
wrist(
s)
(0.0294).
In
addition,
non
ossified
thumb,
an
anomaly,
was
noted
at
an
increased
incidence
(0.0294)
relative
to
concurrent
controls
(0).
In
the
absence
of
historical
control
data,
these
findings
are
considered
treatment
related.
In
addition,
it
could
not
be
determined
how
many
of
these
nominally
increased
incidences
were
from
different
litters,
which
would
have
increased
concern
for
developmental
toxicity.
The
developmental
toxicity
LOAEL
is
125
mg/
kg/
day,
based
on
possible
skeletal
abnormalities
and
total
abnormalies.
The
developmental
toxicity
NOAEL
is
50
mg/
kg/
day.
The
developmental
toxicity
study
in
the
rabbit
is
classified
unacceptable/
upgradable,
pending
submission
of
acceptable
purity,
concentration,
stability
and
litter
data
and
historical
control
data.
A
letter
dated
9/
26/
01
from
the
registrant
provided
no
additional
information
about
this
rabbit
developmental
toxicity
study
other
than
that
the
doses
were
not
analyzed
and
that
a
repeat
rabbit
developmental
toxicity
was
currently
being
conducted.
5.4
Reproductive
Toxicity
5.4.1
Executive
Summary:
In
a
two
generation
reproduction
study,
hexazinone
(98%
a.
i.,
Lot
No.
T02118994)
was
administered
to
groups
of
30
male
and
30
female
Sprague
Dawley
rats
in
the
diet
at
concentrations
of
0,
200,
2000,
or
5000
ppm
(MRID
42066501).
One
litter
was
produced
in
the
first
generation
and
two
litters
were
produced
in
the
second
generation.
Test
substance
intake
for
the
treated
F0
20
groups
was
11.8,
117,
and
294
mg/
kg/
day,
respectively,
for
males
and
14.3,
143,
and
383
mg/
kg/
day,
respectively,
for
females.
Test
substance
intake
for
the
treated
F1
groups
was
15.3,
154,
and
399
mg/
kg/
day,
respectively,
for
males
and
17.7,
180,
and
484
mg/
kg/
day,
respectively,
for
females.
F0
and
F1
parental
animals
were
administered
test
or
control
diet
for
73
or
105
days,
respectively,
prior
to
mating,
throughout
mating,
gestation,
and
lactation,
and
until
necropsy.
Deaths
of
several
F0
and
F1
parental
animals
were
considered
incidental
to
treatment.
No
treatmentrelated
clinical
signs
of
toxicity
were
observed
in
the
adult
animals
of
either
generation.
Gross
necropsy
was
unremarkable
and
no
microscopic
lesions
were
observed
in
selected
tissues
from
the
reproductive
tracts
of
male
and
female
parental
animals.
Body
weights
and
body
weight
gains
of
the
F0
males
were
not
affected
by
treatment.
Premating
body
weight
gains
by
the
mid
and
high
dose
F0
females
were
76%
and
62%
(p
#
0.05
for
both),
respectively,
of
the
control
level
resulting
in
final
premating
body
weights
93%
and
87%
(p
#
0.05),
respectively,
of
the
controls.
Body
weights
of
the
high
dose
F1
males
and
females
were
significantly
reduced
(p
#
0.05)
during
the
premating
interval
with
overall
weight
gains
87%
and
82%,
respectively,
of
the
control
group
amounts.
Reductions
in
body
weights
and
body
weight
gains
during
premating
for
the
mid
and
high
dose
F0
and
highdose
F1
dams
continued
during
gestation
and
lactation.
Food
consumption
during
premating
was
similar
between
the
treated
and
control
groups
for
males
and
females
of
both
generations.
However,
during
gestation
significantly
(p
#
0.05)
lower
food
consumption
was
noted
for
the
high
dose
F1
dams
during
production
of
both
litters
and
for
the
mid
dose
F1
dams
during
production
of
the
second
litter.
There
was
a
statistically
significant
increase
in
absolute
P0
testes
weight
that
appeared
to
be
dose
related,
but
a
nominally
decrease
absolute
F1
adult
testes
weight
in
the
5000
ppm
dose
groups.
The
F1
testes
weight
change
did
not
appear
to
dose
related.
The
testes
weight
changes
in
males
would
appear
to
be
incidental.
Therefore,
the
systemic
toxicity
LOAEL
is
2000
ppm
(117
154
mg/
kg/
day
for
males
and
143
180
mg/
kg/
day
for
females)
based
on
reduced
body
weight
and
body
weight
gains
by
F1
males
and
F0
and
F1
females.
The
systemic
toxicity
NOAEL
is
200
ppm
(11.8
15.3
mg/
kg/
day
for
males
and
14.3
17.7
mg/
kg/
day
for
females).
No
reproductive
effects
were
seen
in
the
study
except
for
the
weight
effects
on
offspring.
Live
birth
and
viability
indices
and
litter
survival
were
similar
between
the
treated
and
control
groups.
The
lactation
index
for
the
F2b
high
dose
litters
was
85.8%
(p
#
0.05)
compared
to
97.5%
for
the
control
group.
Pup
body
weights
were
decreased
throughout
lactation
in
the
mid
and
high
dose
groups
of
all
litters
as
compared
with
the
control
groups
with
statistical
significance
(p
#
0.05)
attained
at
most
time
points.
The
lower
pup
body
weights
were
more
pronounced
in
females
than
in
males.
F1
and
F2a
female
pup
weights
were
statistically
significantly
decreased
at
birth,
day
7
and
14
of
lactation
at
$2000
ppm.
There
were
no
obvious
reproductive
effects
other
than
the
pup
weight
decrement.
Therefore,
the
offspring
LOAEL
is
2000
ppm
(117
154
mg/
kg/
day
for
males
and
143
180
mg/
kg/
day
for
females)
based
on
reduced
female
pup
body
weights
at
birth
and
during
lactation.
The
reproductive
toxicity
NOAEL
was
200
ppm
(11.8
15.3
mg/
kg/
day
for
males
and
14.3
17.7
mg/
kg/
day
for
females).
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
guideline
requirements
for
a
reproductive
toxicity
study
[OPPTS
870.3800
(§
83
4)]
in
rats.
21
5.5
Additional
Information
from
Literature
Sources
(if
available)
The
published
literature
found
on
hexazinone
were
the
papers
on
the
same
studies
submitted
to
the
Agency
[
Kennedy,
GL
and
Kaplan,
AM
(1984)
Chronic
Toxicity,
Reproductive,
and
Teratogenic
Studies
of
Hexazinone.
Fundemental
and
applied
Toxicology
4,
960
971.].
No
other
relevant
literature
on
the
toxicity
was
found.
5.6
Determination
of
Susceptibility
No
quantitative
or
qualitative
evidence
of
increased
susceptibility
was
seen
following
in
utero
exposure
to
rats
or
rabbits,
and
following
pre/
post
natal
exposure
to
rats.
The
rabbit
study,
even
though
classified
as
unacceptable
because
of
technical
deficiencies,
did
not
show
evidence
of
increased
susceptibility.
Never
theless
the
HIARC
noted
that
the
lack
of
an
acceptable
non
rodent
study
is
a
data
gap
for
FQPA
assessment.
5.7
Determination
of
the
Need
for
Developmental
Neurotoxicity
Study
The
weight
of
evidence
does
not
suggest
the
need
for
a
Developmental
Neurotoxicity
study.
5.7.1
Evidence
that
suggest
requiring
a
Developmental
Neurotoxicity
study:
1.
The
structurally
related
pesticide,
Atrazine,
causes
CNS
related
changes
in
prolactin
secretion,
which
is
related
to
reproductive
senescence
in
Sprague
Dawley
rats
through
continuous
estrus
from
decreasing
LH
release,
but
this
effect
would
require
a
special
study
and
would
not
be
detected
by
a
neurotoxicity
study.
5.7.2
Evidence
that
do
not
support
the
need
for
a
Developmental
Neurotoxicity
study
1.
No
evidence
of
neurotoxicity
was
seen
in
either
developmental
toxicity
study
in
the
rat
or
rabbit.
2.
A
12
13%
absolute
female
brain
decrement
was
seen
in
the
chronic
dog
study,
but
the
brain
weight
decrement
was
associated
with
severe
body
weight
decrement.
The
brain
weight
decrement
may
have
been
secondary
to
the
malnutrition
in
these
animals
and
not
directly
due
to
neurotoxic
effects
of
hexazinone
3.
No
neurotoxic
signs
were
seen
in
any
of
the
other
toxicity
studies
with
hexazinone
6.
HAZARD
CHARACTERIZATION
22
Hexazinone
is
a
herbicide
used
to
control
a
broad
spectrum
of
weeds
including
woody
plants
in
alfalfa,
rangeland,
pastures,
woodlands,
pineapple,
sugarcane
and
blue
berries.
Non
crop
areas
include
ornamental
plants
and
forests.
Hexazinone
is
used
as
a
pre
emergent,
post
emergence
herbicide
as
well
as
by
direct
spray
and
soil
applications.
There
are
no
non
occupational
(residential)
uses.
The
pesticide
is
classified
with
the
triazine
herbicides.
The
selectivity
of
triazine
herbicides
depends
on
the
plant's
ability
to
degrade
or
metabolize
the
parent
compound.
Sensitive
plants
have
limited
ability
to
metabolize
hexazinone.
Hexazinone
acts
through
inhibition
of
photosynthesis.
Hexazinone
has
low
acute
toxicity
by
the
oral
(Category
III),
dermal
(Category
IV
)
and
inhalation
routes
(Category
III).
Primary
eye
irritation
is
severe,
causing
corneal
opacity
and
moderate
irritation
in
unwashed
eyes
(Category
I).
It
causes
mild
skin
irritation
and
is
classified
Category
IV
for
skin
irritation.
It
is
not
a
skin
sensitizer
in
the
Guinea
pig.
Body
weight
decrement
and
liver
toxicity
were
the
most
frequent
effects
shown
in
studies
with
hexazinone.
Liver
toxicity
was
seen
in
the
chronic
dog
and
mouse
studies.
Body
weight
decrement
was
seen
in
the
chronic
rat
studies
and
the
studies
on
reproduction.
In
a
reproduction
study,
pup
weight
decrement
occurred
at
the
same
dose
as
parental
body
weight
decrement.
No
reproductive
effects
were
seen
in
the
study
other
than
pup
weight
decrement.
Prenatal
studies
in
the
rat
and
rabbit
showed
no
increased
fetal
susceptibility.
The
rat
prenatal
study
showed
fetal
weight
decrement
and
possibly
renal
malformations.
The
rabbit
study
possibly
showed
skeletal
anomalies
and
delayed
ossifications
at
the
highest
dose
tested.
Thus,
there
is
no
increased
quantitative
or
qualitative
susceptibility
in
reproduction
study
or
prenatal
developmental
toxicity
studies.
The
21
day
dermal
study
in
the
rabbit
showed
no
systemic
toxicity
and
mild
dermal
irritation
at
the
limit
dose.
The
chronic
study
in
dogs
showed
severe
body
weight
decrement,
changes
in
liver
related
clinical
chemistry
values,
and
microscopic
lesions.
Body
weight
decrement
was
seen
in
a
chronic
carcinogenicity
studies
in
rats
and
mice.
Liver
toxicity
was
seen
in
mice.
The
mouse
carcinogenicity
study
showed
an
increased
trend
for
liver
carcinomas,
but
no
pair
wise
significant
increases.
The
rat
study
showed
no
carcinogenic
potential.
Based
on
these
studies
in
rats
and
mice,
hexazinone
was
classified
in
a
group
D,
not
classifiable
as
a
carcinogen.
Rat
metabolism
studies
showed
that
hexazinone
was
rapidly
absorbed
and
excreted
and
essentially
no
difference
in
the
metabolism
of
males
and
females
at
high
or
low
dose
levels.
Almost
no
parent
hexazinone
was
recovered
in
urine
or
feces.
Two
major
metabolites
were
recovered
from
feces
and
urine,
in
addition
to
lesser
amounts
of
a
third
metabolite
and
small
amounts
conjugated
products
from
urine.
6.0
Data
Gaps
The
HIARC
requested
a
28
day
inhalation
study
with
hexazinone
because
of
the
concern
for
potential
inhalation
exposure
based
on
the
use
pattern..
The
rabbit
developmental
toxicity
study
is
classified
as
unacceptable.
Another
study
in
the
rabbit,
requested
by
Cal
EPA,
is
expected
to
be
submitted
to
OPP
as
well.
23
7.0
ACUTE
TOXICITY
Acute
Toxicity
of
Hexazinone
Guideline
No.
Study
Type
MRIDs
#
Results
Toxicity
Category
81
1
Acute
Oral/
Rat
41235004
(1989)
LD50
=
1200
mg/
kg
III
81
2
Acute
Dermal/
Rabbit
00104974
LD50
>5278
mg/
kg
IV
81
3
Acute
Inhalation
00104975
(1973)
LC50
>
7.50
mg/
L(
1
hour)
LC50
>1.9
mg/
L
1
Equivalent
to
340
mg/
kg
2
III
81
4
Primary
Eye
Irritation
00106003
(1982)
Irreversible
corneal
opacity,
Severe
3
I
81
5
Primary
Skin
Irritation
00106004
(1982)
Mild
IV
81
6
Dermal
Sensitization
41235005
(1989)
NA
Not
a
skin
sensitizer
81
8
Acute
Neurotoxicity
Not
conducted
1
One
hour
inhalation
study
on
technical
converted
to
probable
no
effects
at
4
hours.
Consistent
with
an
unreviewed
three
week
inhalation
study
(MRID#
00063972)
showing
no
significant
toxic
effects.
The
effects
seen
were
consistent
with
dust
inhalation
at
2.5
mg/
mL,
the
only
dose
tested.
Another
acute
4
hour
inhalation
study
in
rats
showed
no
effects
at
3.9
mg/
L
using
a
25%
a.
i.
granular
product
(MRID#
41756701).
2
Calculated
by
the
reviewer
from
the
following
information
from
Whalan
(1998).
This
conversion
generally
is
not
considered
valid,
especially
for
irritating
substances.
{[(
1.9
mg/
L
x
1
x
9.13
x
4
x
1)/(
0.204
kg)]
=
340
mg/
kg}
3
The
toxicity
category
was
based
on
the
corneal
opacity.
Irritation
not
counting
opacity
was
tox
category
III.
24
25
8.0
SUMMARY
OF
TOXICOLOGY
ENDPOINT
SELECTION
The
doses
and
toxicological
endpoints
selected
for
various
exposure
scenarios
are
summarized
below.
EXPOSURE
SCENARIO
DOSE
(mg/
kg/
day)
ENDPOINT
STUDY
Acute
Dietary
NOAEL=
400
mg/
kg/
day
UF
=
100
LOAEL=
900
mg/
kg/
day
based
on
decreased
male
and
female
fetal
weight,
kidneys
with
no
papilla
(malformation)
and
misaligned
sternebrae
(variation)
Developmental
Toxicity
Study
in
rats
MRID#
40397501
Acute
RfD
=
4.0
mg/
kg
Chronic
Dietary
NOAEL
=5.0
mg/
kg/
day
UF
=
100
LOAEL=
37.6
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Chronic
One
Year
Feeding
study
in
dogs
MRID#
42162301
Chronic
RfD
=
0.05
mg/
kg/
day
Incidental
Oral,
Short
and
Intermediate
Term
No
residential
uses;
endpoints
not
selected
Dermal,
ShortTerm
NOAEL=
No
hazard
was
identified,
therefore
quantification
of
risk
is
not
required.
No
systemic
toxicity
was
seen
at
the
limit
dose
following
repeat
dermal
application.
Dermal,
Intermediate
Term
1
Oral
NOAEL=
5.0
mg/
kg/
day
UF=
100
LOAEL=
37.6
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase
Chronic
One
Year
Feeding
study
in
dogs
MRID#
42162301
Dermal,
Long
Term
1
Oral
NOAEL=
5.0
Mg/
kg/
day
UF=
100
LOAEL=
37.6
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase
Chronic
One
Year
Feeding
study
in
dogs
MRID#
42162301
26
Inhalation,
ShortTerm
2
Oral
NOAEL=
100
mg/
kg/
day
UF=
100
LOAEL=
400
mg/
kg/
day
based
on
decrease
maternal
food
consumption
and
dose
related
body
weight
decrement.
Developmental
Toxicity
Study
in
rats
MRID#
40397501
Inhalation,
Intermediate
Term
&
Long
Term
2
Oral
NOAEL=
5.0
mg/
kg/
day
UF=
100
LOAEL=
37.6
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Chronic
One
Year
Feeding
study
in
dogs
MRID#
42162301
1
Since
the
endpoint
was
chosen
from
an
oral
study,
assume
25%
dermal
absorption
factor
should
be
used
for
route
to
route
exposures.
3
Since
the
endpoint
was
chosen
from
an
oral
study,
100%
inhalation
absorption
factor
should
be
used
for
route
to
route
exposures.
On
the
dermal
absorption
factor
for
hexazinone:
December
12,
2001
It
does
not
make
sense
to
chose
the
range
finding
study
over
the
main
study.
The
main
study
was
unacceptable
primarily
because
of
the
inability
to
determine
the
number
of
affected
litters
while
the
range
finding
and
main
study
both
suffer
from
a
lack
of
dosage
analysis.
In
addition,
choosing
a
LOAEL
which
includes
a
dose
causing
50%
maternal
mortality
(2/
4)
is
problematic.
At
least
the
main
study
was
conducted
on
16
pregnant
females
at
the
27
LOAEL
and
the
LOAEL
was
more
comparable
with
lower
bound
of
the
LOAEL
of
1000
mg/
kg/
day
in
the
21
day
dermal
study.
Thus,
if
12.5%
dermal
absorption
factor
had
been
used
(125/
1000x100),
adequate
protection
of
workers
from
the
developmental
effects
seen
in
rats
would
still
be
apparent.
Rabbit
maternal
LOAEL/
dermal
lower
bound
LOAEL=
125/
1000
=
12.5%
.
Developmental
NOAEL
of
400
mg/
kg/
day/
0.125
=3200
mg/
kg/
day
which
is
also
higher
than
1000
mg/
kg/
day,
which
is
the
objective,
I
think.
| epa | 2024-06-07T20:31:42.893046 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0014/content.txt"
} |
EPA-HQ-OPP-2002-0188-0015 | Supporting & Related Material | "2002-09-16T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
May
1,
2002
MEMORANDUM
SUBJECT:
Review
of
Hexazinone
Incident
Reports
DP
Barcode
D282798,
Chemical
#107201
FROM:
Jerome
Blondell,
Ph.
D.,
Health
Statistician
Chemistry
and
Exposure
Branch
1
Health
Effects
Division
(7509C)
Monica
F.
Spann,
M.
P.
H.,
Environmental
Health
Scientist
Chemistry
and
Exposure
Branch
1
Health
Effects
Division
(7509C)
THRU:
Francis
B.
Suhre,
Senior
Scientist
Chemistry
and
Exposure
Branch
1
Health
Effects
Division
(7509C)
TO:
Carol
Christensen,
Environmental
Protection
Specialist
Reregistration
Branch
2
Health
Effects
Division
(7509C)
BACKGROUND
The
following
data
bases
have
been
consulted
for
the
poisoning
incident
data
on
the
active
ingredient
Hexazinone
(PC
Code:
107201):
1)
OPP
Incident
Data
System
(IDS)
reports
of
incidents
from
various
sources,
including
registrants,
other
federal
and
state
health
and
environmental
agencies
and
individual
consumers,
submitted
to
OPP
since
1992.
Reports
submitted
to
the
Incident
Data
System
represent
anecdotal
reports
or
allegations
only,
unless
otherwise
stated.
Typically
no
conclusions
can
be
drawn
implicating
the
pesticide
as
a
cause
of
any
of
the
reported
health
effects.
Nevertheless,
sometimes
with
enough
cases
and/
or
enough
documentation
risk
mitigation
measures
may
be
suggested.
2
2)
Poison
Control
Centers
as
the
result
of
a
data
purchase
by
EPA,
OPP
received
Poison
Control
Center
data
covering
the
years
1993
through
1998
for
all
pesticides.
Most
of
the
national
Poison
Control
Centers
(PCCs)
participate
in
a
national
data
collection
system,
the
Toxic
Exposure
Surveillance
System
which
obtains
data
from
about
65
70
centers
at
hospitals
and
universities.
PCCs
provide
telephone
consultation
for
individuals
and
health
care
providers
on
suspected
poisonings,
involving
drugs,
household
products,
pesticides,
etc.
3)
California
Department
of
Pesticide
Regulation
California
has
collected
uniform
data
on
suspected
pesticide
poisonings
since
1982.
Physicians
are
required,
by
statute,
to
report
to
their
local
health
officer
all
occurrences
of
illness
suspected
of
being
related
to
exposure
to
pesticides.
The
majority
of
the
incidents
involve
workers.
Information
on
exposure
(worker
activity),
type
of
illness
(systemic,
eye,
skin,
eye/
skin
and
respiratory),
likelihood
of
a
causal
relationship,
and
number
of
days
off
work
and
in
the
hospital
are
provided.
4)
National
Pesticide
Telecommunications
Network
(NPTN)
NPTN
is
a
toll
free
information
service
supported
by
OPP.
A
ranking
of
the
top
200
active
ingredients
for
which
telephone
calls
were
received
during
calendar
years
1984
1991,
inclusive
has
been
prepared.
The
total
number
of
calls
was
tabulated
for
the
categories
human
incidents,
animal
incidents,
calls
for
information,
and
others.
HEXAZINONE
REVIEW
I.
Incident
Data
System
Please
note
that
the
following
cases
from
the
IDS
do
not
have
documentation
confirming
exposure
or
health
effects
unless
otherwise
noted.
Incident#
956
1
A
pesticide
incident
occurred
in
1994,
when
an
individual
reported
burning
and
red
welts
on
their
legs
after
using
a
backpack
sprayer
that
was
leaking
on
his
hip
while
applying
the
product.
No
further
information
on
the
disposition
of
the
case
was
reported.
Incident#
3172
1
A
pesticide
incident
occurred
in
1996,
when
utility
workers
were
exposed
to
the
product
for
about
one
to
one
and
a
half
hours
after
a
tank
mixture
was
sprayed
in
the
area
close
to
where
they
were
working.
The
workers
reported
temporary
eye
irritation.
No
further
information
on
the
disposition
of
the
case
was
reported.
Incident#
3645
1
A
pesticide
incident
occurred
in
1996,
when
a
worker,
who
was
not
wearing
gloves
but
was
wearing
boots,
reported
peeling
skin
on
their
hands
and
feet.
The
worker
was
applying
the
product
that
got
onto
their
hands
and
feet.
No
further
information
on
the
disposition
of
the
case
was
reported.
3
Incident#
9945
6
A
pesticide
incident
occurred
in
1999,
when
a
field
was
sprayed
with
the
product
within
a
half
mile
of
a
couple's
home.
Specific
symptoms
were
not
mentioned.
No
further
information
on
the
disposition
of
the
case
was
reported.
II.
Poison
Control
Center
Data
1993
through
1998
Results
for
the
years
1993
through
1998
were
acquired
for
17
exposures
to
hexazinone
reported
to
Poison
Control
Centers.
Cases
involving
exposures
to
multiple
products
are
excluded.
No
cases
were
reported
among
children
under
six
years
of
age
and
4
cases
among
older
children
and
adults
exposed
at
their
workplace.
One
of
the
four
cases
reported
a
moderate
outcome
with
eye
effects
that
resulted
in
being
seen
in
a
health
care
facility.
This
was
too
few
cases
to
warrant
detailed
analysis.
There
were
13
non
occupationally
exposed
cases
among
older
children
and
adults.
Of
these
cases,
5
had
outcome
determined
of
which
none
reported
a
serious
or
even
a
moderate
outcome.
One
should
be
cautious
about
drawing
conclusions
from
such
a
small
number
of
cases.
III.
California
Data
1982
through
1999
Detailed
descriptions
of
1
case
submitted
to
the
California
Pesticide
Illness
Surveillance
Program
(1982
1999)
were
reviewed.
In
the
case,
a
worker
reported
breathing
difficulties
and
was
diagnosed
with
bronchitis
and
slight
asthma
after
hexazinone
was
applied
to
the
ground.
Hexazinone
ranked
208
th
as
a
cause
of
systemic
poisoning
in
California
based
on
data
for
1982
through
1999.
IV.
National
Pesticide
Telecommunications
Network
On
the
list
of
the
top
200
chemicals
for
which
NPTN
received
calls
from
1984
1991
inclusively,
hexazinone
was
ranked
159
th
with
17
incidents
in
humans
reported
and
2
in
animals
(mostly
pets).
V.
Conclusions
Relatively
few
incidents
of
illness
have
been
reported
due
to
hexazinone.
VI.
Recommendations
No
recommendations
can
be
made
based
on
the
few
incident
reports
available.
4
cc:
Correspondence
Hexazinone
file
(chemical
no.
107201)
Dirk
Helder,
SRRD
(7508C)
| epa | 2024-06-07T20:31:42.902389 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0015/content.txt"
} |
EPA-HQ-OPP-2002-0188-0016 | Supporting & Related Material | "2002-09-16T04:00:00" | null | OFFICE
OF
PREVENTION,
PESTICIDES,
AND
TOXIC
SUBSTANCES
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
DATE:
April
25,
2002
SUBJECT:
Hexazinone.
The
Outcome
of
the
HED
Metabolism
Assessment
Review
Committee
for
Water.
PC
code
107201;
Rereg.
Case
0266;
DP
Barcode:
D282111;
TXR
No.
0050425.
FROM:
Sherrie
L.
Kinard,
Chemist
Reregistration
Branch
II
Health
Effects
Division
(7509C)
THROUGH:
Al
Nielsen,
Branch
Senior
Scientist
Reregistration
Branch
II
Health
Effects
Division
(7509C)
TO:
Christine
Olinger,
Chair
Metabolism
Assessment
Review
Committee
(MARC)
Health
Effects
Division
(7509C)
MATERIAL
REVIEWED
The
MARC
met
on
January
29,
2002
and
then
again
on
March
12,
2002
to
consider
residues
of
hexazinone
[3
cyclohexyl
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione]
and
metabolites
in/
on
plant
and
animal
comodities
and
in
water.
Specifically,
MARC
determined
which
metabolites
should
be
included
in
the
tolerance
expression
and
risk
assessment.
MARC
CONCLUSIONS
The
Committee
concluded
that
hexazinone
plus
metabolites
A,
B,
C,
D,
and
E
(calculated
as
hexazinone)
are
the
residues
of
concern
to
be
included
in
tolerance
expression
and
risk
assessment
for
plants
and
rotational
crops.
The
residues
of
concern
to
be
included
in
the
tolerance
expression
for
ruminants
are
hexazinone
plus
metabolites
B,
C,
C
2,
and
F
in
milk,
and
hexazinone
plus
metabolites
B
and
F
in
tissue.
For
purposes
of
risk
assessment,
the
residues
of
concern
in/
on
ruminants
are
hexazinone
plus
metabolites
B,
C,
C
1,
C
2,
and
F.
The
Agency
has
previously
determined
that
tolerances
in
poultry
commodities
and
a
poultry
feeding
study
are
not
required
for
reregistration
based
on
results
of
reviewed
poultry
metabolism
data.
For
water,
the
Committee
concluded
that
for
risk
assessment
purposes,
hexazinone,
G3170,
and
all
metabolites
with
conjoined
cyclohexyl
and
triazine
rings
should
be
included.
Hexazinone
HED
MARC
Meeting
Summary
Chart:
Chemical:
Hexazinone
Date:
29
Jan
2002
Residues
of
Concern
Matrix
For
Risk
Assessment
For
Tolerance
Expression
Plants
Parent,
metabolites
A,
B,
C,
D,
and
E
Parent,
metabolites
A,
B,
C,
D,
and
E
Rotational
crop
Parent,
metabolites
A,
B,
C,
D,
and
E
Parent,
metabolites
A,
B,
C,
D,
and
E
Poultry
Not
Required
Not
Required
Ruminant
Parent,
metabolites
B,
C,
C
1,
C
2,
and
F
For
milk:
Parent,
B,
C,
C
2
and
F
For
tissue:
Parent,
B,
and
F
Water
Not
discussed
N/
A
Chemical:
Hexazinone
Date:
12
March
2002
Residues
of
Concern
Matrix
For
Risk
Assessment
For
Tolerance
Expression
Water
Parent,
G3170,
and
all
metabolites
with
conjoined
cyclohexyl
and
triazine
rings.
N/
A
RATIONALE
Plant:
Hexazinone
and
metabolites
A,
B,
C,
D,
and
E
are
detected
in
plant
metabolism
studies.
Toxicity
data
are
not
available
for
these
metabolites,
and
MARC
assumed
they
have
potentially
similar
toxicity
to
the
parent
due
to
the
similarities
in
structure.
These
metabolites
are
also
measured
by
the
enforcement
method;
in
addition,
metabolites
A
D
and
F
were
observed
in
the
rat
metabolism
study.
MARC
concluded
that
for
risk
assessment
and
tolerance
expression,
hexazinone
plus
metabolites
A,
B,
C,
D,
and
E
are
the
residues
of
concern.
Rotational
crop:
Hexazinone
and
metabolites
F,
G,
H,
G3170,
G3170
NG,
A
1,
1,
and
C
1
were
also
found
in
field
rotational
crop
studies,
in
addition
to
the
parent,
A,
B,
C,
D,
and
E;
however,
metabolites
F,
G,
H,
G3170,
G3170
NG,
A
1,
1,
and
C
1
were
below
the
LOQ
in
the
field
studies.
The
MARC
concluded
that
these
low
level
metabolites
are
not
likely
to
be
significantly
more
toxic
than
the
parent
and
can
therefore
be
excluded.
Ruminant:
Metabolites
B,
C
1,
C
2,
and
F
are
the
major
metabolites
(>
10%
TRR)
found
in
milk
and
tissue
in
the
goat
metabolism
study;
therefore,
the
MARC
concluded
that
hexazinone
plus
these
metabolites
need
to
be
included
in
the
risk
assessment.
Since
the
enforcement
method
detects
only
parent,
B,
C,
C
2,
and
F
in
milk,
and
parent,
B,
and
F
in
tissues,
MARC
recommended
that
for
milk
tolerance
expression,
the
residues
of
concern
are
hexazinone
plus
metabolites
B,
C,
C
2,
and
F,
and
for
livestock
tissues
tolerance
expression,
the
residues
of
concern
are
hexazinone
plus
metabolites
B,
and
F.
Although
the
Committee
previously
(5/
19/
94)
recommended
inclusion
of
metabolites
A,
D
and
E
in
animal
commodities,
these
moieties
each
represented
<1
to
4%
of
the
total
residues
in
goat
milk
and
tissues.
Poultry:
No
decision
is
needed
at
this
time
(40CFR180.6(
a)
(3)).
Water:
Environmental
fate
data
suggest
that
the
parent
and
degradates
are
likely
to
be
persistent
and
mobile
in
the
environment.
Leaching
and
runoff
are
expected
to
be
primary
dissipation
routes.
Metabolites
A,
B,
D,
1
(JS472),
and
2
(JT677)
are
major
metabolites
(>
10%
TRR)
found
in
soil/
aquatic
studies.
Metabolites
A
1,
C
and
G3170
are
detected
in
ground
water
analysis.
Due
to
lack
of
toxicity
data
for
these
metabolites,
MARC
assumes
they
have
similar
toxicity
as
the
parent
because
of
the
structure
similarities
(except
G3170).
G3170
was
detected
at
the
highest
level
in
the
California
prospective
groundwater
study
(PGW)
and
there
are
no
toxicity
information
available
to
indicated
that
it
is
of
less
toxicological
concern
than
the
parent.
Therefore,
MARC
concludes
that
parent,
G3170,
and
all
degradates
with
conjoined
cyclohexyl
and
triazine
rings
(specifically,
A,
A
1,
B,
C,
D,
1
(JS472),
and
2
(JT677))
are
residues
of
concern
for
risk
assessment
in
water.
ATTENDEES
Members
in
Attendance
(January
29,
2002):
Abdallah
Khasawinah,
Yan
Donovan,
David
Nixon,
Rick
Loranger,
Leung
Cheng,
John
Doherty,
Sheila
Piper,
Bill
Wassell,
William
Dykstra
(alternate).
Members
Not
Present:
Alberto
Protzel,
Christine
Olinger,
Norman
Birchfield.
Non
Members
in
Attendance:
David
Anderson,
Sherrie
Kinard,
Diana
Locke,
Dirk
Helder,
Pauline
Wagner,
Larry
Liu.
Members
in
Attendance
(March
12,
2002):
Abdallah
Khasawinah,
Christine
Olinger,
Norman
Birchfield,
Yan
Donovan,
David
Nixon,
Rick
Loranger,
Leung
Cheng,
John
Doherty,
Sheila
Piper.
Members
Not
Present:
Bill
Wassell,
Alberto
Protzel,
Leonard
Keifer.
Non
Members
in
Attendance:
Dirk
Helder,
Sherrie
Kinard,
Larry
Liu.
cc:
SF,
RF,
List
A
File,
S.
Kinard
(RRB2),
D.
Anderson
(RRB2),
Diana
Locke
(RRB2),
L.
Liu
(EFED)
RDI:
C.
Olinger:
04/
25/
02;
A.
Nielson:
04/
25/
02.
7509C:
RRB2:
S.
Kinard:
CM#
2:
Rm
722B:
703
305
0563:
04/
25/
02.
| epa | 2024-06-07T20:31:42.905560 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0016/content.txt"
} |
EPA-HQ-OPP-2002-0188-0017 | Supporting & Related Material | "2002-09-16T04:00:00" | null | N
N
N
N
O
O
2
15
02
MEMORANDUM
SUBJECT:
Hexazinone.
List
A
Reregistration
Case
0266.
PC
Code
107201.
Product
Chemistry
Chapter
for
the
Tolerance
Reassessment
Eligibility
Decision
[TRED]
Document.
DP
Barcode
D279324.
FROM:
K.
Dockter,
Chemist
Reregistration
Branch
2
Health
Effects
Division
[7509C]
THRU:
Alan
Nielsen,
Branch
Senior
Scientist
Reregistration
Branch
2
Health
Effects
Division
[7509C]
TO:
Diana
Locke,
Ph.
D.,
Risk
Assessor
Reregistration
Branch
2
Health
Effects
Division
[7509C]
Hexazinone
[3
cyclohexyl
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione]
is
a
contact
and
residual
herbicide.
"Apply
when
plants
are
actively
growing
for
control
of
many
annual,
biennial
and
perennial
weeds
and
woody
plants
on
noncropland
areas.
Gives
contact
and
residual
control.
Rainfall
is
needed
for
soil
activation.
Controls
woody
plants
in
reforestation
areas
(site
preparation
or
conifer
release);
selective
weed
control
in
conifers,
sugarcane,
pineapple,
rubber
trees,
alfalfa,
blueberries."
Farm
Chemicals
Handbook,
1999
Empirical
formula:
C12H20N4O2
Molecular
weight:
252.3
CAS
Registry
No.:
51235
04
2
PC
Code:
107201
Chemical
structure
by
J.
Punzi
A
search
of
REFS
conducted
12/
07/
01
identified
a
single
hexazinone
technical
[T]
registered
2
under
PC
Code
107201,
the
Dupont
98.7
%
T;
EPA
Reg.
No.
352
399.
It
is
subject
to
a
TRED.
The
pre
FQPA
Reregistration
Eligibility
Decision
Document
issued
9/
94.
The
Registration
Standard
+
FRSTR
issued
6/
88;
the
Update
issued
5/
10/
91.
The
product
chemistry
data
base
is
essentially
complete.
There
are
no
reported
impurities
of
toxicological
concern
in
hexazinone.
The
Series
830
physical
and
chemical
properties
are
given
in
the
table
below.
GLN
MRID
Data
6302
Color
41203201
white
6303
Physical
state
"
crystalline
solid
6304
Odor
"
mildly
pungent
7200
MP
"
113.5
C
7300
Bulk
density
"
0.61
g/
mL
7840
Water
solubility
"
2.98
g/
100g
@
25
C
7950
vp
"
1.9
x
10
7
mm
Hg
@
25
C
7550
Pow
"
15
at
pH
7.0
6313
Stability
"
stable
in
slightly
acidic
or
alkaline
media
at
elevated
temperatures,
slowly
degrades
under
artificial
sunlight.
~1%
decomposition
when
stored
2
yrs
under
ambient
conditions.
7370
Dissociation
constants
in
water
"
a
very
weak
base
7000
pH
"
8.0
6320
Corrosion
characteristics
"
0.18
34
mils/
yr
@
50
C
in
various
metals;
no
change
in
packaging
materials.
3
cc:
Reg.
Std.
file,
RF,
Dockter,
S.
Kinard,
D.
Anderson.
RD\
I
Hexazinone
TRED
Team.
7509C:
RRB2:
Rm712G:
57886:
KD/
kd
Hexazinone.
TRED
[992f8]
=
D279324.
mem.
| epa | 2024-06-07T20:31:42.908038 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0017/content.txt"
} |
EPA-HQ-OPP-2002-0188-0018 | Supporting & Related Material | "2002-09-16T04:00:00" | null | N
N
N
N
O
O
R
E
V
I
S
E
D
4
23
02
MEMORANDUM
SUBJECT:
Hexazinone.
List
A
Reregistration
Case
0266.
PC
Code
107201.
Product
Chemistry
Chapter
for
the
Tolerance
Reassessment
Eligibility
Decision
[TRED]
Document.
DP
Barcode
D279324.
FROM:
K.
Dockter,
Chemist
Reregistration
Branch
2
Health
Effects
Division
[7509C]
THRU:
Alan
Nielsen,
Branch
Senior
Scientist
Reregistration
Branch
2
Health
Effects
Division
[7509C]
TO:
Carol
Christensen,
Risk
Assessor
Reregistration
Branch
2
Health
Effects
Division
[7509C]
Hexazinone
[3
cyclohexyl
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione]
is
a
contact
and
residual
herbicide.
"Apply
when
plants
are
actively
growing
for
control
of
many
annual,
biennial
and
perennial
weeds
and
woody
plants
on
noncropland
areas.
Gives
contact
and
residual
control.
Rainfall
is
needed
for
soil
activation.
Controls
woody
plants
in
reforestation
areas
(site
preparation
or
conifer
release);
selective
weed
control
in
conifers,
sugarcane,
pineapple,
rubber
trees,
alfalfa,
blueberries."
Farm
Chemicals
Handbook,
1999
Empirical
formula:
C12H20N4O2
Molecular
weight:
252.3
CAS
Registry
No.:
51235
04
2
PC
Code:
107201
2
Chemical
structure
by
J.
Punzi
A
search
of
REFS
conducted
12/
07/
01
identified
a
single
hexazinone
technical
[T]
registered
under
PC
Code
107201,
the
Dupont
98.7
%
T;
EPA
Reg.
No.
352
399.
It
is
subject
to
a
TRED.
The
pre
FQPA
Reregistration
Eligibility
Decision
Document
issued
9/
94.
The
Registration
Standard
+
FRSTR
issued
6/
88;
the
Update
issued
5/
10/
91.
The
product
chemistry
data
base
is
essentially
complete.
There
are
no
reported
impurities
of
toxicological
concern
in
hexazinone.
The
Series
830
physical
and
chemical
properties
are
given
in
the
table
below.
GLN
MRID
Data
6302
Color
41203201
white
6303
Physical
state
"
crystalline
solid
6304
Odor
"
mildly
pungent
7200
MP
"
113.5
C
7300
Bulk
density
"
0.61
g/
mL
7840
Water
solubility
"
2.98
g/
100g
@
25
C
7950
vp
"
1.9
x
10
7
mm
Hg
@
25
C
7550
Pow
"
15
at
pH
7.0
6313
Stability
"
stable
in
slightly
acidic
or
alkaline
media
at
elevated
temperatures,
slowly
degrades
under
artificial
sunlight.
~1%
decomposition
when
stored
2
yrs
under
ambient
conditions.
7370
Dissociation
constants
in
water
"
a
very
weak
base
7000
pH
"
8.0
3
6320
Corrosion
characteristics
"
0.18
34
mils/
yr
@
50
C
in
various
metals;
no
change
in
packaging
materials.
cc:
Reg.
Std.
file,
RF,
Dockter,
S.
Kinard,
D.
Anderson.
RD\
I
Hexazinone
TRED
Team.
7509C:
RRB2:
Rm712G:
57886:
KD/
kd
Hexazinone.
TRED
[26]
=
D279324.
mem.
| epa | 2024-06-07T20:31:42.910733 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0018/content.txt"
} |
EPA-HQ-OPP-2002-0188-0019 | Supporting & Related Material | "2002-09-16T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
05/
20/
2002
SUBJECT:
Hexazinone
Residue
Chemistry
Chapter
for
the
Tolerance
Reassessment
Eligibility
Decision
(TRED);
PC
Code
107201;
DP
Barcode
D279899;
Rereg.
Case
0266.
FROM:
John
S.
Punzi,
Ph.
D.,
Chemist
Reregistration
Branch
II
Health
Effects
Division
(7509C)
THROUGH:
Alan
Nielsen,
Branch
Senior
Scientist
Reregistration
Branch
II
Health
Effects
Division
(7509C)
and
Chemistry
Science
Advisory
Council
(Chem
SAC)
05/
15/
2002
Health
Effects
Division
(7509C)
TO:
Carol
Christensen,
Risk
Assessor
Reregistration
Branch
II
Special
Review
and
Reregistration
Division
(7509C)
and
Dirk
Helder,
Chemical
Review
Manager
Reregistration
Branch
II
Special
Review
and
Reregistration
Division
(7508W)
cc:
JSPunzi
(RRB2),
Hexazinone
Reg.
Std.
File,
Hexazinone
SF,
RF,
LAN.
RD/
I:
RRB2
Chem
Review
Team
(05/
12/
2002),
Alan
Nielsen
(05/
25/
2002).
7509C:
RRB2:
John
S.
Punzi:
CM2:
Rm
712M:
703
305
7727:
05/
08/
2002.
INTRODUCTION
Hexazinone
[3
cyclohexyl
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
is
a
triazine
dione
herbicide
registered
for
use
on
alfalfa,
blueberries,
pasture
and
range
grasses,
pineapple,
and
sugarcane.
It
is
also
registered
for
use
on
ornamental
plants,
forest
trees,
and
noncrop
areas.
Hexazinone
is
a
proprietary
chemical
of
E.
I.
du
Pont
de
Nemours
and
Company,
Inc.
which
is
the
sole
producer
and
primary
registrant
of
this
broad
spectrum
herbicide.
The
dry
flowable
(DF),
emulsifiable
concentrate
(EC),
and
soluble
concentrate
(SC)
are
the
formulation
classes
registered
to
du
Pont
with
food/
feed
uses.
These
formulations,
sold
under
the
trade
name
Velpar®,
may
be
applied
for
preemergence,
postemergence,
layby,
directed
spray,
or
basal
soil
treatments
using
ground
or
aerial
equipment.
EXECUTIVE
SUMMARY
OF
RESIDUE
CHEMISTRY
DATA
REQUIREMENTS
The
10/
8/
93
Residue
Chemistry
Chapter
required
label
amendments
for:
(1)
alfalfa
to
specify
a
30
day
preharvest
interval
(PHI)
for
the
feeding
of
forage
and
cutting
of
hay;
(2)
blueberries
to
specify
PHIs
of
90
and
450
days
for
highbush
and
lowbush
varieties,
respectively.
These
label
revisions
remain
outstanding.
Details
of
the
required
label
amendments
are
presented
in
the
respective
endnote
for
GLN
860.1500
(Crop
Field
Trials)
in
Table
B.
Data
depicting
magnitude
of
the
residues
of
hexazinone
and
metabolites
A,
B,
C,
D,
and
E
in/
on
grass
forage
and
hay
harvested
0
day
following
a
single
broadcast
application
of
representative
formulations
at
1.125
lb
ai/
A
are
required.
GLN
860.1300:
Nature
of
the
Residue
Plants
The
qualitative
nature
of
the
residue
in
plants
is
adequately
understood.
Studies
indicate
that
root
uptake
is
the
principal
mechanism
for
the
absorption
of
hexazinone
by
plants
from
soils.
Hexazinone
is
translocated
through
the
xylem
to
the
foliage
where
it
blocks
the
photosynthetic
process.
The
HED
Metabolism
Assessment
Review
Committee
(MARC)
concluded
that
the
hexazinone
tolerance
expression
for
plants
and
rotational
crops
should
include
hexazinone
and
metabolites
A,
B,
C,
D,
and
E
(see
Figure
1
for
structures
and
proper
nomenclature).
Toxicity
data
for
the
metabolites
is
not
available;
but,
based
on
the
structural
similarity
of
the
metabolites,
it
is
assumed
they
will
exhibit
similar
toxicity
to
the
parent
hexazinone.
The
current
tolerance
expression
for
hexazinone
in
40
CFR
§180.396
is
for
"combined
residues
of
the
herbicide
hexazinone
(3
cyclohexyl
6(
dimethylamino)
1
methyl
1,3,5
triazine2,4
1H,
3H)
dione)
and
its
metabolites,
calculated
as
hexazinone."
The
tolerance
expression
should
be
modified
to
include
specific
metabolites
A,
B,
C,
D,
and
E,
identified
by
the
appropriate
name.
GLN
860.1300:
Nature
of
the
Residue
Livestock
The
qualitative
nature
of
the
residue
in
livestock
is
adequately
understood
based
on
acceptable
ruminant
and
poultry
metabolism
studies.
The
HED
MARC
concluded
that
the
hexazinone
tolerance
expression
for
ruminants
should
include
hexazinone
plus
metabolites
B,
C,
C
2,
and
F
for
milk.
The
Committee
concluded
that
the
hexazinone
tolerance
expression
for
ruminant
tissue
should
include
hexazinone
plus
metabolites
B
and
F.
The
Committee
concluded
that
residues
of
hexazinone
and
metabolites
B,
C,
C1
C
2,
and
F
should
be
taken
into
account
when
risk
assessments
are
done.
GLN
860.1340:
Residue
Analytical
Methods
Plant
Commodities
Adequate
methods
are
available
for
purposes
of
data
collection
and
enforcement
of
tolerances
for
residues
of
hexazinone
and
metabolites
A,
B,
C,
D,
and
E
in/
on
plant
commodities.
Livestock
Commodities
The
registrant
has
proposed
an
LC/
MS
method
(designated
as
du
Pont
AMR
3783
96)
as
an
enforcement
method
for
livestock
commodities.
The
method
has
been
subjected
to
a
successful
ILV
and
a
radiovalidation
study
and
will
be
forwarded
to
the
Analytical
Chemistry
Branch
for
a
tolerance
method
validation
by
Agency
chemists.
If
the
results
of
method
validation
by
Agency
chemists
are
successful,
then
Method
AMR
3783
96
will
be
proposed
for
inclusion
in
PAM
Volume
II,
and
no
additional
data
concerning
this
GLN
topic
will
be
required
for
reregistration.
GLN
860.1360:
Multiresidue
Methods
The
reregistration
requirements
for
multiresidue
methods
data
are
fulfilled.
GLN
860.1380:
Storage
Stability
Plant
Commodities
No
additional
storage
stability
data
for
plant
and
processed
commodities
are
required
for
reregistration.
Livestock
Commodities
Adequate
storage
stability
data
are
available
to
support
the
existing
ruminant
feeding
study.
GLN
860.1500:
Crop
Field
Trials
Berries
Group
Blueberry
The
10/
8/
93
Residue
Chemistry
Chapter
concluded
that
no
additional
data
are
required
for
blueberries
provided
all
pertinent
product
labels
are
amended
to
specify
PHIs
of
90
and
450
days
for
application
to
highbush
and
lowbush
blueberries,
respectively.
Based
on
the
combined
LOQs
(0.55
ppm)
of
the
enforcement
method
for
parent
plus
metabolites,
HED
recommends
that
the
RAC
tolerance
be
increased
from
0.2
ppm
to
0.60
ppm.
Grass
Forage,
Fodder,
and
Hay
Group
Grass
(pasture
and
rangeland)
forage
An
examination
of
registered
uses
of
hexazinone
on
pasture
and
rangeland
grasses
(see
Table
A2)
reveal
that
there
two
distinct
use
patterns,
a
basal
soil
application
and
a
broadcast
application.
It
is
noted
that
the
10
ppm
tolerance
for
grass
forage
(listed
as
"grasses,
pasture"
and
"grasses,
range"
under
40
CFR
§180.396)
was
established
based
on
residue
data
reflecting
basal
soil
application
only.
In
the
absence
of
residue
data
reflecting
broadcast
application,
HED
is
requiring
the
following
additional
data
for
grass
forage
before
the
RAC
tolerance
can
be
reassessed:
Data
depicting
magnitude
of
the
residues
of
hexazinone
and
metabolites
A,
B,
C,
D,
and
E
in/
on
grass
forage
harvested
0
day
following
a
single
broadcast
application
of
representative
formulations
at
1.125
lb
ai/
A.
It
is
HED
policy
to
require
0
day
crop
field
residue
data
for
grass
forage
unless
it
is
not
feasible
(e.
g.,
preplant/
preemergence
pesticide
uses).
The
formulations
to
be
tested
may
be
applied
in
side
by
side
plots.
The
location
and
number
of
trials
should
be
in
compliance
with
the
current
OPPTS
GLN
for
adequate
geographic
representation
of
data.
Grass
(pasture
and
rangeland)
hay
The
reregistration
requirements
for
residue
data
on
grass
hay
have
not
been
fulfilled.
The
registrant
has
submitted
a
petition
(PP#
1F3967),
for
the
establishment
of
a
tolerance
for
residues
of
hexazinone
and
its
metabolites
in/
on
grass
hay.
The
petition
is
currently
in
reject
status
because
grass
hay
data,
from
field
trials
with
adequate
geographical
representation,
remain
outstanding.
Since
1991
HED
has
reviewed
two
proposals
to
amend
the
original
petition
requesting
that
the
Agency
establish
tolerances
for
grass
hay
based
on
theoretical
grass
drying
factors.
HED
recommended
against
the
establishment
of
grass
hay
tolerances
each
time.
In
addition,
HED
reviewed
two
registrant
responses
to
the
petition
amendment
reviews
and
concluded
in
each
case
that
the
recommendation
to
require
actual
field
trial
data
for
grass
hay
is
appropriate.
Non
Grass
Animal
Feeds
(Forage,
Fodder,
Straw,
and
Hay)
Group
Alfalfa
forage
and
hay
The
Updated
Table
A
for
Residue
Chemistry
RED
Chapter
dated
9/
8/
94
concluded
that
adequate
residue
data
are
available
for
alfalfa
forage
and
hay.
However,
label
amendments
were
required
on
all
product
labels
for
alfalfa,
including
supplemental
labels,
to
establish
a
30
day
PHI
for
the
feeding
of
forage
and
the
cutting
of
hay.
The
available
residue
data
indicate
that
the
combined
residues
of
hexazinone
and
its
metabolites
A,
B,
C,
D,
and
E
in/
on
treated
samples
were
<1.87
ppm
and
<3.33
ppm
for
alfalfa
forage
and
hay,
respectively.
Based
on
these
data,
the
established
tolerance
for
alfalfa
forage
is
reassessed
at
its
existing
level
of
2.0
ppm;
however,
the
tolerance
for
alfalfa
hay
should
be
lowered
from
8.0
ppm
to
4.0
ppm.
Table
A2
shows
that
product
labels
for
the
90%
SC
(EPA
Reg.
No.
352
378)
and
75%
DF
(EPA
Reg.
No.
352
58)
formulations
have
been
revised
in
compliance
with
previously
requested
label
amendment.
However,
the
product
label
for
the
2
lb/
gal
EC
(EPA
Reg.
No.
352
392)
formulation
does
not
specify
any
PHI;
this
label
must
be
amended
to
establish
a
30
day
PHI
(or
pregrazing
interval)
for
the
feeding
of
forage
and
the
cutting
of
hay.
Alfalfa
seed
The
available
residue
data
indicate
that
the
combined
residues
of
hexazinone
and
its
regulated
metabolites
ranged
from
<1.30
ppm
to
<1.46
ppm
in/
on
alfalfa
seed
following
a
single
broadcast
dormant
application
of
the
2
lb/
gal
EC
or
90%
SC
formulation
at
0.75
lb
ai/
A
(1.5x
the
maximum
registered
rate
on
alfalfa
grown
for
seed);
no
data
were
submitted
reflecting
1.0x.
HED
is
requesting
the
registrant
to
propose
a
tolerance
for
hexazinone
residues
of
concern
in/
on
alfalfa
seed
of
2.0
ppm.
Miscellaneous
Pineapple
The
available
data
indicate
that
the
combined
residues
of
hexazinone
and
its
regulated
metabolites
were
<0.35
ppm
in/
on
pineapple
fruits
harvested
at
a
minimum
PHI
of
181
days
following
five
ground
applications
of
a
representative
hexazinone
formulation
at
0.45
0.9
lb
ai/
A
for
a
total
rate
of
3.6
lb
ai/
A.
Based
on
the
combined
LOQs
(0.55
ppm)
of
the
enforcement
method,
HED
is
now
recommending
that
the
RAC
tolerance
be
increased
from
0.5
ppm
to
0.60
ppm.
Sugarcane
The
available
data
indicate
that
the
combined
residues
of
hexazinone
and
its
regulated
metabolites
were
<0.35
ppm
in/
on
samples
of
sugarcane
treated
with
the
90%
SC
formulation
of
hexazinone
from
the
following
test
locations:
(i)
in
Puerto
Rico
where
sugarcane
was
harvested
288
days
following
a
single
postemergence
application
at
0.45
lb
ai/
A
(0.5x
the
maximum
registered
seasonal
rate
for
this
area);
(ii)
in
TX
where
sugarcane
was
harvested
234
days
following
one
preemergence
application
followed
by
one
postemergence
application
at
0.675
lb
ai/
A/
application
(0.75x
the
maximum
seasonal
rate
in
TX);
and
(iii)
in
HI
where
sugarcane
was
harvested
179
181
days
following
a
total
of
four
applications
(one
preemergence
application
at
1.35
or
1.47
lb
ai/
A,
a
postemergence
application
at
0.45
lb
ai/
A/
application,
followed
by
two
postemergence
applications
at
1.8
lb
ai/
A/
application)
for
a
total
rate
of
5.4
5.5
lb
ai/
A/
season
(1.5x
the
maximum
seasonal
rate
in
HI).
Based
on
the
combined
LOQs
(0.55
ppm)
of
the
enforcement
method,
HED
is
now
recommending
that
the
RAC
tolerance
be
increased
from
0.20
ppm
to
0.60
ppm.
GLN
860.1520:
Processed
Food/
Feed
Pineapple
process
residue
and
juice
Residues
of
hexazinone
and
its
regulated
metabolites
did
not
concentrate
in
pineapple
process
residue
and
juice
except
for
Metabolite
B
in
process
residue.
The
registrant
calculated
a
concentration
factor
of
3.0x
for
Metabolite
B
in
pineapple
process
residue
based
on
quantified
residues
of
0.06
ppm
in
pineapple
process
residue
and
0.02
ppm
in/
on
pineapple
RAC
after
treatment
with
hexazinone
at
a
1.0x
rate.
When
this
concentration
factor
of
3.0x
is
multiplied
by
the
highest
average
field
trial
(HAFT)
residue
of
<0.05
ppm,
the
maximum
expected
residues
of
metabolite
B
in
pineapple
process
residue
is
0.15
ppm
which
is
less
than
the
reassessed
RAC
tolerance
of
0.60
ppm.
Therefore,
no
tolerance
for
pineapple
process
residues
is
warranted.
Sugarcane
molasses
and
refined
sugar
An
acceptable
sugarcane
processing
study
is
available.
Following
processing
of
the
RAC
according
to
simulated
commercial
practices,
residues
of
hexazinone
and/
or
metabolites
A
through
E
concentrated
in
"A
molasses"
(4.0x).
However,
residues
declined
in
raw
sugar
(reduction
factor
of
0.2x)
and
processed
sugar
(reduction
factor
of
0.2x).
Adjusting
for
the
degree
of
exaggeration
(2.0x)
used
in
the
processing
study,
the
residue
for
blackstrap
molasses
is
3.83
ppm.
The
available
data
suggest
that
the
established
tolerance
for
sugarcane
molasses
should
be
decreased
from
5.0
ppm
to
4.0
ppm.
GLN
860.1480:
Meat,
Milk,
Poultry,
and
Eggs
The
results
of
ruminant
metabolism
study
suggest
significant
transfer
of
hexazinone
residues
of
concern
to
meat
and
milk.
The
registrant
has
submitted
a
dairy
cattle
feeding
study
(MRID
43703501)
which
was
deemed
acceptable.
HED
is
recommending
that;
in
order
to
reassess
the
established
hexazinone
tolerances
for
milk
and
the
fat,
meat,
and
meat
byproducts
of
livestock
and
to
compute
a
maximum
theoretical
dietary
burden
(MTDB)
of
hexazinone
to
livestock,
uses
on
pasture
and
rangeland
grasses
be
cancelled.
A
MTDB
could
not
be
calculated
including
grass
and
grass
hay
since
additional
residue
data
are
required
for
use
patterns
for
which
significant
residues
are
expected
in/
on
the
RACs.
HED
recognizes
that
the
estimated
100,000
acres
of
pasture
and
rangeland
treated
with
hexazinone
is
relatively
low.
However,
since
grass
and
grass
hay
are
considered
major
dietary
components
of
ruminants
(up
to
60%
of
the
diet
per
current
OPPTS
GLN),
a
MTDB
for
livestock
could
not
be
developed
when
grasses
are
included.
HED
has
determined
that
a
MTDB
could
be
constructed
from
potential
feed
items
for
livestock
and
subsequently
tolerances
for
meats
and
milk
can
be
reassessed.
HED
has
previously
determined
that
tolerances
in
poultry
commodities
and
a
poultry
feeding
study
are
not
required
for
reregistration
based
on
results
of
reviewed
poultry
metabolism
data.
A
brief
summary
of
the
reviewed
dairy
cattle
feeding
study
(MRID
43703501)
is
presented
below.
Three
groups
of
dairy
cows
(3
animals/
dose
group)
were
dosed
with
hexazinone
at
29,
87,
and
290
ppm
in
the
diet
for
28
consecutive
days;
three
additional
cows
served
as
control
animals.
These
dose
levels
are
equivalent
to
6.25x,
18.75x,
and
62.5x,
respectively,
the
MTDB
for
beef
and
dairy
cattle.
These
dose
levels
are
equivalent
to
64x,
190x,
and
640x
the
MTDB
for
hogs.
The
maximum
total
hexazinone
residues
in
milk
were
0.78
ppm
at
the
6.25x
feeding
level
(29
ppm
in
the
diet)
and
11.09
ppm
at
the
62.5x
level.
On
day
14,
after
total
residues
had
reached
plateaus,
milk
was
separated
into
skim
milk
and
cream.
Total
residues
in
skim
milk
were
comparable
to
those
in
whole
milk;
total
residues
in
cream
were
approximately
half
those
in
skim
milk.
In
tissues,
the
maximum
total
hexazinone
residues
at
the
62.5x
feeding
level
were
3.85
ppm
in
liver,
2.19
ppm
in
kidney,
0.32
ppm
in
muscle,
and
nondetectable
(
#
0.10
ppm)
in
fat.
The
maximum
total
residues
at
the
6.25x
feeding
level
were
0.24
ppm
in
liver,
0.47
ppm
in
kidney,
and
nondetectable
(
#
0.15
ppm)
in
muscle.
Because
total
residues
were
nondetectable
in
all
fat
samples
from
the
18.75x
and
62.5x
levels,
fat
samples
were
not
analyzed
at
lower
feeding
levels.
A
tolerance
of
0.5
ppm
is
presently
established
for
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone)
in
milk.
Based
on
the
MTDB
for
beef
and
dairy
cattle
without
grass
or
grass
hay
as
a
potential
feed
item,
it
is
possible
to
reassess
the
animal
commodity
tolerances.
The
HED
Metabolism
Assessment
Review
Committee
has
concluded
that
the
hexazinone
tolerance
expression
for
ruminants
should
include
hexazinone
plus
metabolites
B,
C,
C
2,
and
F
for
milk.
Residue
levels
of
hexazinone
and
metabolites
in
whole
milk
from
the
feeding
study
corrected
for
exaggeration
levels
ranged
from
0.110
ppm
to
0.164
ppm.
Based
on
the
enforcement
method,
the
sum
of
the
LOQ's
for
hexazinone
and
metabolites
B,
C,
C
2,
and
F
is
0.20
ppm
;
therefore
it
is
appropriate
that
the
tolerance
for
milk
be
reduced
from
0.5
to
0.20
ppm.
Tolerances
of
0.1
ppm
are
presently
established
for
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone)
in
meat.
Residue
levels
of
hexazinone
and
metabolites
in
muscle
from
the
feeding
study
corrected
for
exaggeration
levels
ranged
from
0.003
ppm
to
0.039
ppm.
Based
on
the
enforcement
method,
the
sum
of
the
LOQ's
for
hexazinone
and
metabolites
B
and
F
is
0.10
ppm
therefore
it
is
appropriate
that
the
tolerance
for
meat
byproducts
of
cattle,
goats,
horses,
and
sheep
be
reassessed
at
0.10
ppm.
Residue
levels
of
hexazinone
and
metabolites
in
muscle
from
the
feeding
study
corrected
for
exaggeration
levels
ranged
from
0.0004
ppm
to
0.002
ppm
therefore
tolerances
for
hog
meat
are
not
required.
Tolerances
of
0.1
ppm
are
presently
established
for
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone)
in
meat
byproducts
of
cattle,
goats,
hogs,
horses,
and
sheep.
Residue
levels
of
hexazinone
and
metabolites
in
kidney
from
the
feeding
study
corrected
for
exaggeration
levels
ranged
from
0.046
ppm
to
0.090
ppm.
Based
on
the
enforcement
method,
the
sum
of
the
LOQ's
for
hexazinone
and
metabolites
B
and
F
is
0.10
ppm;
therefore,
it
is
appropriate
that
the
tolerance
for
meat
byproducts
of
cattle,
goats,
horses,
and
sheep
be
reassessed
at
0.10
ppm.
Residue
levels
of
hexazinone
and
metabolites
in
kidney
from
the
feeding
study
corrected
for
exaggeration
levels
ranged
from
0.003
ppm
to
0.007
ppm
therefore
tolerances
for
hog
meat
byproducts
are
not
required
and
should
be
revoked.
Tolerances
of
0.1
ppm
are
presently
established
for
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone)
in
fat.
Residue
levels
of
hexazinone
and
metabolites
in
fat
from
the
feeding
study
were
nondetectable
<0.1
ppm
at
the
62.5x
exaggerated
rate.
HED
has
determined
that
tolerances
for
hexazinone
residues
in
fat
of
cattle,
goats,
hogs,
horses,
and
sheep
are
not
required.
Tolerances
for
fat
of
cattle,
goats,
hogs,
horses,
and
sheep
are
not
required
and
should
be
revoked.
GLN
860.1850:
Confined
Accumulation
in
Rotational
Crops
The
data
requirements
for
confined
rotational
crops
are
satisfied.
GLN
860.1900:
Field
Accumulation
in
Rotational
Crops
The
data
requirements
for
field
accumulation
in
rotational
crops
are
only
partially
satisfied.
This
conclusion
is
based
on
a
recent
review
of
a
limited
field
crop
rotation
study
wherein
the
75%
DF
formulation
of
hexazinone
was
applied
as
a
single
postemergence
broadcast
application
to
mowed
alfalfa
at
1.5
lb
ai/
A
(1x
the
maximum
seasonal
rate
for
alfalfa).
Approximately
one
year
following
application,
the
remaining
alfalfa
crop
residue
was
plowed
up
and
returned
to
the
soil,
and
head
lettuce,
field
corn,
and
wheat
were
planted.
Residues
were
below
the
respective
method
LOQs
for
hexazinone
and
metabolites
A,
B,
C,
D,
E,
F,
G,
H,
G3170,
G3170
NG,
A
1,
and
C
1
in/
on
head
lettuce,
wheat
forage
and
grain,
and
field
corn
forage
and
grain.
In
wheat
straw,
residues
of
metabolite
B
were
<0.02
0.021
ppm;
residues
of
hexazinone
and
the
remaining
metabolites
were
below
the
LOQ.
In
field
corn
stover,
residues
of
hexazinone
were
0.02
0.081
ppm,
residues
of
metabolite
B
were
0.038
0.053
ppm,
and
residues
of
the
remaining
metabolites
were
below
the
LOQ.
These
data
indicate
that
extended
field
rotational
crop
studies
and
rotational
crop
tolerances
will
not
be
required
for
residues
of
hexazinone
residues
of
concern
in/
on
leafy
vegetables
provided
that
labels
are
amended
to
specify
a
rotational
crop
restriction
of
at
least
12
months.
A
previous
review
of
a
confined
rotational
crop
study
concluded
that
rotational
crop
tolerances
were
not
needed
for
root
crops
provided
that
a
12
month
plantback
interval
was
established;
an
examination
of
the
basic
registrant's
labels
shows
that
the
12
month
plantback
interval
for
root
crops
has
been
established.
Because
the
data
from
the
limited
field
trials
indicate
that
quantifiable
residues
occur
in
field
corn
stover
and
wheat
straw,
extended
field
rotational
crop
trials
for
corn
stover,
sorghum
stover,
and
wheat
straw
to
support
a
12
month
rotational
interval
and
a
tolerance
for
inadvertent
hexazinone
residues
are
required.
HEXAZINONE
TRED:
RESIDUE
CHEMISTRY
CONSIDERATIONS
PC
Code
107201;
Case
0266
(DP
Barcode
279899)
TABLE
OF
CONTENTS
page
INTRODUCTION
.........................................................
1
REGULATORY
BACKGROUND
............................................
1
SUMMARY
OF
SCIENCE
FINDINGS........................................
2
GLN
860.1200:
Directions
for
Use
......................................
2
Product
List
....................................................
2
Food/
Feed
Use
Pattern
Table
.......................................
3
Rotational
Crop
Restrictions
.......................................
4
GLN
860.1300:
Nature
of
the
Residue
Plants
............................
12
GLN
860.1300:
Nature
of
the
Residue
Livestock
.........................
16
GLN
860.1340:
Residue
Analytical
Methods
.............................
18
Plant
Commodities
..............................................
18
Animal
Commodities
............................................
19
GLN
860.1360:
Multiresidue
Methods
..................................
20
GLN
860.1380:
Storage
Stability
Data
..................................
20
Plant
Commodities
..............................................
20
Animal
Commodities
............................................
21
GLN
860.1500:
Crop
Field
Trials
......................................
21
Berries
Group..................................................
21
Blueberry
................................................
21
Grass
Forage,
Fodder,
and
Hay
Group
..............................
22
Grass
(pasture
and
rangeland)
forage...........................
22
Grass
(pasture
and
rangeland)
hay.............................
22
Non
Grass
Animal
Feeds
(Forage,
Fodder,
Straw,
and
Hay)
Group
........
23
Alfalfa
forage
and
hay
......................................
23
Alfalfa
seed
..............................................
23
Miscellaneous
Commodities
......................................
24
Pineapple
................................................
24
Sugarcane
................................................
24
GLN
860.1520:
Processed
Food/
Feed
...................................
25
Pineapple
process
residue
and
juice............................
25
Sugarcane
molasses
and
refined
sugar..........................
25
GLN
860.1480:
Meat,
Milk,
Poultry,
and
Eggs
............................
26
Maximum
theoretical
dietary
burden
(tentative)
..................
26
Table
of
Contents
(continued)
page
ix
Dairy
cattle
feeding
study
...................................
27
GLN
860.1400:
Water,
Fish,
and
Irrigated
Crops
..........................
28
GLN
860.1460:
Food
Handling
........................................
28
GLN
860.1850:
Confined
Accumulation
in
Rotational
Crops
.................
28
GLN
860.1900:
Field
Accumulation
in
Rotational
Crops
....................
28
TOLERANCE
REASSESSMENT
SUMMARY
................................
35
Tolerances
Listed
Under
40
CFR
§180.396
(a)
.............................
36
Tolerances
Needed
Under
40
CFR
§180.396
(a)
...........................
36
Tolerances
Listed
Under
40
CFR
§180.396
(c)
.............................
36
CODEX
HARMONIZATION
..............................................
38
AGENCY
MEMORANDA
CITATIONS
.....................................
39
STUDY
CITATIONS
.....................................................
45
N
N
N
O
O
CH
3
N
CH
3
CH
3
HEXAZINONE
TRED
REPORT
ON
FQPA
TOLERANCE
REASSESSMENT
PROGRESS
AND
INTERIM
RISK
MANAGEMENT
DECISION:
RESIDUE
CHEMISTRY
CONSIDERATIONS
PC
Code
107201;
Case
0266
INTRODUCTION
Hexazinone
[3
cyclohexyl
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)dione
is
a
triazine
dione
herbicide
registered
for
use
on
alfalfa,
blueberries,
pasture
and
range
grasses,
pineapple,
and
sugarcane.
It
is
also
registered
for
use
on
ornamental
plants,
forest
trees,
and
noncrop
areas.
Hexazinone
is
a
proprietary
chemical
of
E.
I.
du
Pont
de
Nemours
and
Company,
Inc.
(Dupont)
which
is
the
sole
producer
and
primary
registrant
of
this
broad
spectrum
herbicide.
The
dry
flowable
(DF),
emulsifiable
concentrate
(EC),
and
soluble
concentrate
(SC)
are
the
formulation
classes
registered
to
du
Pont
with
food/
feed
uses.
These
formulations,
sold
under
the
trade
name
Velpar®,
may
be
applied
as
preemergence,
postemergence,
layby,
directed
spray,
or
basal
soil
treatments
using
ground
or
aerial
equipment.
REGULATORY
BACKGROUND
Hexazinone
was
first
registered
by
the
Agency
in
November
1975
for
general
weed
control
in
non
cropland
areas.
Uses
on
Christmas
trees
and
forest
trees
were
added
in
1977.
Use
patterns
for
the
culture
of
sugarcane
and
alfalfa
were
conditionally
registered
in
1980
and
1981,
respectively.
The
Agency
has
issued
several
regulatory
documents
summarizing
the
reregistration
status
of
hexazinone.
In
February
1982,
the
Agency
issued
a
Pesticide
Registration
Standard
for
hexazinone
which
identified
data
gaps
according
to
guidelines
then
in
place.
After
issuance
of
the
1982
Standard,
new
uses
for
hexazinone
were
established
on
blueberries,
rangeland
and
pasture
grasses,
and
pineapple.
A
second
Registration
2
Standard
was
issued
in
September,
1988
(NTIS#
PB89
126080).
The
1988
Standard
summarized
available
data
supporting
the
registration
of
products
containing
hexazinone
as
the
active
ingredients
and
required
additional
residue
chemistry
data
among
other
requirements.
Hexazinone
was
also
the
subject
of
a
Final
Registration
Standard
and
Tolerance
Reassessment
(FRSTR)
Residue
Chemistry
Chapter
dated
5/
25/
88,
a
Reregistration
Standard
Update
to
the
Residue
Chemistry
Chapter
dated
9/
5/
91,
and
Product
and
Residue
Chemistry
Chapters
for
Hexazinone
Reregistration
Eligibility
Decision
(RED)
document
in
10/
8/
93.
An
Updated
Table
A
for
Hexazinone
Residue
Chemistry
Chapter
RED
was
issued
in
9/
8/
94
in
order
to
reflect
the
conclusions
of
reviews
completed
since
the
RED
Chapter
was
completed.
The
10/
8/
93
Residue
Chemistry
Chapter
to
the
Hexazinone
RED
required
label
revisions
for
alfalfa,
blueberry,
pineapple,
and
sugarcane
in
order
to
reflect
use
pattern
parameters
for
which
residue
data
are
available.
In
addition,
the
10/
8/
93
Residue
Chapter
required
additional
residue
chemistry
data
pertaining
to:
animal
metabolism
(additional
data
were
required
to
upgrade
an
existing
ruminant
study);
residue
analytical
methods
(an
enforcement
method
is
required
for
determination
of
hexazinone
residues
of
concern
in
milk,
meat,
and
meat
byproducts
of
ruminants);
storage
stability
(alfalfa
and
certain
metabolites
for
grass);
magnitude
of
the
residue
in/
on
grass
hay,
sugarcane,
and
in
the
processed
commodities
of
pineapple
and
sugarcane;
and
rotational
crops.
The
basic
registrant,
DuPont,
has
submitted
most
of
the
requested
residue
chemistry
data
which
have
been
evaluated
by
HED.
This
document
is
a
comprehensive
update
to
the
10/
8/
93
Residue
Chapter,
and
the
information
contained
herein
incorporates
HED's
conclusions
of
recently
reviewed
residue
chemistry
studies
as
well
as
a
reassessment
of
hexazinone
tolerances,
as
mandated
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996.
Hexazinone
tolerances
are
established
under
40
CFR
§180.396
(a)
and
(b).
The
tolerance
expression,
for
plant
and
animal
commodities,
is
in
terms
of
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone).
An
adequate
enforcement
method
is
available
for
determination
of
regulated
hexazinone
residues
in/
on
plants.
The
registrant
has
proposed
an
LC/
MS
method
(designated
as
du
Pont
method
AMR
3783
96)
as
an
enforcement
method
for
livestock
commodities.
The
method
has
been
subjected
to
a
successful
ILV
and
a
radiovalidation
study
and
will
be
forwarded
to
the
Analytical
Chemistry
Branch
for
a
tolerance
method
validation
by
Agency
chemists.
If
the
results
of
method
validation
by
Agency
chemists
are
successful,
then
Method
AMR
3783
96
will
be
proposed
for
inclusion
in
PAM
Volume
II,
and
no
additional
data
concerning
this
GLN
topic
will
be
required
for
reregistration.
SUMMARY
OF
SCIENCE
FINDINGS
3
GLN
860.1200:
Directions
for
Use
Product
List
A
search
of
the
Agency's
Reference
Files
System
(REFS)
database,
conducted
on
7/
26/
01,
identified
three
active
hexazinone
end
use
products
(EPs)
registered
to
the
basic
registrant
(DuPont)
under
FIFRA
Section
3
for
use
on
food
and
feed
crops.
There
are
also
eight
products
registered
under
Section
24
(c).
These
products
are
listed
below
in
Table
A1.
Table
A1.
Hexazinone
EPs
with
Uses
on
Feed/
Food
Crops
Registered
to
E.
I.
du
Pont
de
Nemours
and
Company.
EPA
Reg
No.
Label
Acceptance
Date
Formulation
Class
Product
Name
352
378
1
3/
27/
98
90%
SC
DuPont
Velpar
®
Herbicide
352
392
2
5/
22/
01
2
lb/
gal
EC
DuPont
Velpar
®
L
Herbicide
352
581
3
5/
22/
01
75%
DF
DuPont
Velpar
®
DF
Herbicide
1
Including
SLN
TX940008.
2
Including
SLN
ME980002,
MT940001,
NC830012,
and
WY920001.
3
Including
SLN
ME980003,
ND970002,
and
SD970001.
Food/
Feed
Use
Pattern
Table
A
summary
of
hexazinone
food/
feed
use
patterns,
based
on
the
product
labels
registered
to
E.
I.
duPont
de
Nemours
and
Company,
is
presented
in
Table
A2.
The
application
rates
listed
in
Table
A2
depend
on
soil
texture
(coarse,
medium,
and
fine)
and
percent
organic
matter
(OM)
in
the
soil;
a
higher
rate
is
recommended
for
soil
with
organic
matter
greater
than
5%.
Use
on
gravelly
or
rocky
soils,
exposed
subsoils,
hardpan,
sand,
poorly
drained
soil,
or
alkali
soils
is
prohibited.
Unless
otherwise
specified,
applications
may
be
made
in
a
minimum
of
5
gal/
A
by
air
or
in
a
minimum
of
20
gal/
A
using
ground
equipment.
A
tabular
summary
of
the
residue
chemistry
science
assessments
for
reregistration
of
hexazinone
is
presented
in
Table
B.
The
status
of
reregistration
requirements
for
each
guideline
topic
listed
in
Table
B
is
based
on
the
use
patterns
registered
to
the
basic
registrant.
When
end
use
product
DCIs
are
developed
(e.
g.,
at
issuance
of
the
RED),
RD
should
require
that
all
end
use
product
labels
(e.
g.,
MAI
labels,
SLNs,
and
products
subject
to
the
generic
data
exemption)
be
amended
such
that
they
are
consistent
with
the
label
of
the
basic
registrant.
The
10/
8/
93
Residue
Chapter
required
label
amendments
for:
(1)
alfalfa
to
specify
a
30
day
preharvest
interval
(PHI)
for
the
feeding
of
forage
and
cutting
of
hay;
(2)
blueberries
to
specify
PHIs
of
90
and
450
days
for
highbush
and
lowbush
varieties,
respectively;
(3)
pineapple
to
specify
a
maximum
application
rate
of
3.6
lb
4
ai/
A/
cropping
cycle
and
a
minimum
PHI
of
181
days;
(4)
pineapple
forage
to
include
a
pineapple
forage
feeding
restriction;
and
(5)
sugarcane
to
specify
use
rates
if
hexazinone
were
to
be
registered
in
the
state
of
FL.
The
registrant
has
complied
with
some
of
the
previously
requested
label
amendments;
however,
label
revisions
remain
outstanding
for
alfalfa
and
blueberries;
details
of
the
required
label
amendments
are
presented
in
the
respective
endnote
for
GLN
860.1500
(Crop
Field
Trials)
in
Table
B.
Rotational
Crop
Restrictions
The
following
rotational
crop
restrictions
have
been
established
for
the
90%
SC
(EPA
Reg.
No.
352
378),
2
lb/
gal
EC
(EPA
Reg.
No.
352
378),
and
75%
DF
(EPA
Reg.
No.
352
581)
following
use
of
hexazinone
on
alfalfa:
(i)
do
not
replant
treated
areas
to
any
crop
except
corn,
root
crops
or
sugarcane
within
two
years
after
treatment,
as
crop
injury
may
result;
(ii)
corn
may
be
planted
12
months
after
the
last
treatment,
provided
the
use
rate
did
not
exceed
0.75
lb
per
acre,
except
in
areas
of
low
rainfall
(20"
or
less);
(iii)
root
crops
such
as
potatoes,
sugar
beets,
radish
and
carrots
may
be
planted
12
months
after
the
last
treatment,
provided
the
use
rate
did
not
exceed
0.5
lb/
A.
Sites
with
use
rates
higher
than
0.5
lb/
A
should
not
be
replanted
to
any
crop
within
2
years
of
application,
or
unacceptable
crop
injury
may
result;
(iv)
sugarcane
may
be
planted
any
time
following
treatment;
(v)
in
CA,
do
not
replant
seed
alfalfa
areas
to
any
crop
within
two
years
after
treatment,
as
crop
injury
may
result.
Based
on
the
results
of
a
recently
reviewed
field
accumulation
study
(MRID
45084101)
in
rotational
crops,
the
registrant
is
required
to
amend
product
labels
to
establish
a
12
month
plantback
interval
for
leafy
vegetables.
HED
previously
recommended
the
establishment
of
a
12
month
plantback
interval
for
root
crops
based
on
the
results
of
a
confined
rotational
crop
study
(MRID
42824001).
Except
for
the
recommendation
to
establish
a
plantback
interval
of
12
months
for
leafy
vegetables,
the
existing
rotational
crop
restrictions
appear
adequate.
HED
notes
that
the
current
labels
bear
certain
plantback
intervals
of
two
years
for
some
crops
which
apparently
is
largely
or
wholly
based
on
phytotoxicity
considerations.
HED
further
notes
that
the
established
plantback
intervals
are
dependent
on
application
rates
which
are
about
0.5x
or
less
the
maximum
seasonal
rate
for
alfalfa.
Because
the
data
from
the
limited
field
trials
indicate
that
quantifiable
residues
occur
in
field
corn
stover
and
wheat
straw,
extended
field
rotational
crop
trials
for
corn
stover,
sorghum
stover,
and
wheat
straw
to
support
a
12
month
rotational
interval
and
a
tolerance
for
inadvertent
hexazinone
residues
are
required.
5
(continued;
footnotes
follow)
Table
A2.
Food/
Feed
Use
Patterns
Subject
To
Reregistration
for
Hexazinone
(PC
Code
107201).
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Max.
Single
Application
Rate
(lb
ai/
A)
Max.
#
Apps./
Season
Maximum
Seasonal
Rate
(lb
ai/
A)
Preharvest
or
Pregrazing
Interval
(Days)
Use
Directions
and
Limitations
1
Alfalfa
(grown
for
hay)
Broadcast
application
Dormant,
non
dormant,
and
semi
dormant
Ground
or
aerial
90%
SC
[352
378]
1.35
0.675
(for
alfalfa
less
than
one
year
old)
1
1.
35/
year
30
Use
prohibited
in
ND
and
SD.
Broadcast
application
Dormant,
non
dormant,
and
semi
dormant
Ground
or
aerial
2
lb/
gal
EC
[352
392]
75%
DF
[352
581]
1.5
For
the
EC
formulation
only:
0.75
(for
alfalfa
<1
year
old)
1
1.
5/
year
30
(75%
DF
only)
Alfalfa
(grown
for
seed)
Broadcast
application
Dormant,
non
dormant,
and
semi
dormant
Ground
or
aerial
90%
SC
[352
378]
2
lb/
gal
EC
[352
392]
75%
DF
[352
581]
0.5
1
0.5
Not
specified
(NS)
Use
limited
to
CA.
A
maximum
rate
of
0.5
lb
ai/
A
is
specified
for
fields
with
sandy
loam
or
loamy
sand
soils
having
1
2%
OM
and
on
seed
alfalfa
that
has
been
established
for
only
one
growing
season.
Table
A2.
(continued).
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Max.
Single
Application
Rate
(lb
ai/
A)
Max.
#
Apps./
Season
Maximum
Seasonal
Rate
(lb
ai/
A)
Preharvest
or
Pregrazing
Interval
(Days)
Use
Directions
and
Limitations
1
6
(continued;
footnotes
follow)
Alfalfa
(grown
for
forage)
Broadcast
application
Dormant
Ground
2
lb/
gal
EC
[MT940001]
[WY920001]
75%
DF
[ND970002]
[SD970001]
1.0
1
1.0
30
(75%
DF)
Use
limited
to
MT,
ND,
SD,
and
WY
for
established
stands
of
forage
alfalfa.
Application
to
soils
with
<1.5%
OM
is
prohibited
for
the
EC
formulation.
Blueberry
2
Broadcast
application
Spring
of
fruiting
year
(prior
to
budbreak)
Ground
2
lb/
gal
EC
[ME980002]
75%
DF
[ME980003]
2.0
NS
2.
0
450
Use
limited
to
ME
for
established
lowbush
blueberries.
Do
not
exceed
2.0
or
1.8
lb
ai/
A
if
soil
has
been
respectively
treated
with
the
EC
or
DF
formulations
of
hexazinone
within
the
past
8
years.
Broadcast
application
Dormant
(prior
to
budbreak)
Ground
2
lb/
gal
EC
[NC830012]
2.0
NS
NS
50
Use
limited
to
NC.
Application
may
be
made
in
sufficient
water
to
provide
thorough
and
uniform
coverage,
usually
20
gal/
A.
Table
A2.
(continued).
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Max.
Single
Application
Rate
(lb
ai/
A)
Max.
#
Apps./
Season
Maximum
Seasonal
Rate
(lb
ai/
A)
Preharvest
or
Pregrazing
Interval
(Days)
Use
Directions
and
Limitations
1
7
(continued;
footnotes
follow)
Pineapple
Broadcast
or
directed
spray
application
Ground
or
aerial
90%
SC
[352
378]
2
lb/
gal
EC
[352
392]
75%
DF
[352
581]
1.8
NS
3.
6/
crop
cycle
181
Broadcast
applications
may
be
made
between
successive
pineapple
crops,
preplant
after
rows
have
been
mulched,
and
postplant
prior
to
active
growth.
Three
to
ten
months
after
planting,
directed
spray
applications
may
be
made
to
the
soil
between
crop
rows.
Broadcast
applications
may
be
made
in
100
400
gallons
of
water/
A
using
ground
equipment,
or
in
at
least
10
gal/
A
using
aerial
equipment.
Directed
sprays
may
be
applied
at
50
200
gal/
A
using
ground
equipment.
Directed
spot
treatments
are
also
permitted
at
0.9
1.8
lb
ai/
100
gal
prior
to
floral
induction.
Table
A2.
(continued).
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Max.
Single
Application
Rate
(lb
ai/
A)
Max.
#
Apps./
Season
Maximum
Seasonal
Rate
(lb
ai/
A)
Preharvest
or
Pregrazing
Interval
(Days)
Use
Directions
and
Limitations
1
8
(continued;
footnotes
follow)
Pasture
Broadcast
application
Ground
90%
SC
[352
378]
2
lb/
gal
EC
[352
392]
75%
DF
[352
581]
1.125
1
1.
125
(implied)
60
Use
limited
to
Bermuda
grass/
Bahia
grass
pastures.
Applications
may
be
made
in
a
minimum
of
25
gal/
A
using
ground
equipment.
Basal
soil
application
(undiluted)
Ground
2
lb/
gal
EC
[352
392]
2
4
mL
of
product
for
each
inch
of
stem
diameter
NS
0.67/
year
NS
Use
limited
to
brush
control
in
pastures
and
rangelands.
No
restrictions
on
grazing
by
domestic
animals
nor
on
cutting
surrounding
vegetation
for
forage
and
hay
when
product
is
applied
as
a
basal
soil
treatment.
Basal
soil
application
Ground
75%
DF
[352
581]
2
lb/
1
gal
[2
4
mL
of
suspension
for
each
inch
of
stem
diameter]
NS
0.67/
year
NS
Table
A2.
(continued).
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Max.
Single
Application
Rate
(lb
ai/
A)
Max.
#
Apps./
Season
Maximum
Seasonal
Rate
(lb
ai/
A)
Preharvest
or
Pregrazing
Interval
(Days)
Use
Directions
and
Limitations
1
9
(continued;
footnotes
follow)
Rangeland
Basal
soil
application
(undiluted)
Ground
2
lb/
gal
EC
[352
392]
2
4
mL
of
product
for
each
inch
of
stem
diameter
NS
0.67/
year
NS
Use
limited
to
brush
control
in
pastures
and
rangelands.
No
restrictions
on
grazing
by
domestic
animals
nor
on
cutting
surrounding
vegetation
for
forage
and
hay
when
product
is
applied
as
a
basal
soil
treatment.
Basal
soil
application
Ground
75%
DF
[352
581]
2
lb/
1
gal
[2
4
mL
of
suspension
for
each
inch
of
stem
diameter]
NS
0.67/
year
NS
Sugarcane
Broadcast
application
Preemergence
and
postemergence
Ground
or
aerial
90%
SC
[352
378]
2
lb/
gal
EC
[352
392]
75%
DF
[352
581]
3.6
1
3.6/
crop
cycle
(18
24
months)
180
Use
limited
to
HI.
Application
may
be
made
with
a
nonionic
surfactant
at
0.25%
v/
v.
Table
A2.
(continued).
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Max.
Single
Application
Rate
(lb
ai/
A)
Max.
#
Apps./
Season
Maximum
Seasonal
Rate
(lb
ai/
A)
Preharvest
or
Pregrazing
Interval
(Days)
Use
Directions
and
Limitations
1
10
(continued;
footnotes
follow)
Sugarcane
(continued)
Broadcast
application
Preemergence
(in
fall)
and
postemergence
(in
spring
before
active
cane
tillering
begins)
Ground
or
aerial
90%
SC
[352
378]
2
lb/
gal
EC
[352
392]
75%
DF
[352
581]
0.9
NS
0.
45/
year
for
the
90%
SC
1.5/
year
for
the
2
lb/
gal
EC
and
75%
DF
234
Use
limited
to
LA.
Broadcast
application
Preemergence
and
postemergence
Ground
or
aerial
90%
SC
[352
378]
2
lb/
gal
EC
[352
392]
75%
DF
[352
581]
0.45
0.5
NS
0.
9/
crop
cycle
288
Use
limited
to
PR.
Preemergence,
early
postemergence,
and/
or
directed
layby
Ground
or
aerial
90%
SC
[352
378]
2
lb/
gal
EC
[352
392]
75%
DF
[352
581]
0.9
NS
1.
8/
crop
cycle
234
Use
limited
to
TX.
Two
treatments
are
allowed
(one
early
treatment
plus
one
directed
treatment
at
layby),
provided
60
days
have
elapsed
and
at
least
3"
of
rainfall
have
occurred.
Table
A2.
(continued).
Site
Application
Type
Application
Timing
Application
Equipment
Formulation
[EPA
Reg.
No.]
Max.
Single
Application
Rate
(lb
ai/
A)
Max.
#
Apps./
Season
Maximum
Seasonal
Rate
(lb
ai/
A)
Preharvest
or
Pregrazing
Interval
(Days)
Use
Directions
and
Limitations
1
11
Sugarcane
(continued)
Preemergence,
early
postemergence,
or
directed
layby
Ground
or
aerial
90%
SC
[TX940008]
0.45
1
0.
45
NS
Tank
mix
use
with
diuron
(Karmex
DF
Herbicide)
limited
to
TX.
Application
may
be
made
in
a
minimum
of
5
gal/
A
by
air
or
in
a
minimum
of
25
gal/
A
using
ground
equipment.
The
feeding
of
sugarcane
forage
to
livestock
is
prohibited.
Use
on
gravelly
or
rocky
soils,
thinly
covered
subsoils,
coarse
textured
soils
with
<2%
OM,
or
on
any
soil
with
<1%
OM
is
prohibited.
The
planting
of
any
crop
other
than
sugarcane
within
18
months
of
the
last
application
is
prohibited.
1
The
restricted
entry
interval
(REI)
for
the
90%
SC
(EPA
Reg.
No.
352
378),
2
lb/
gal
EC
(EPA
Reg.
No.
352
378),
and
75%
DF
(EPA
Reg.
No.
352
581)
formulations
is
24
hours.
2
A
REFS
search,
conducted
7/
26/
01,
listed
blueberries
as
a
use
site
for
the
Federal
labels
of
the
2
lb/
gal
EC
(EPA
Reg.
No.
352
392)
and
the
90%
SC
(EPA
Reg.
No.
352
378).
However,
upon
label
examination
of
these
products,
it
was
determined
that
there
are
no
Section
3
registrations
of
hexazinone
on
blueberries;
only
Section
24(
c)
registrations
exist.
12
GLN
860.1300:
Nature
of
the
Residue
Plants
The
qualitative
nature
of
the
residue
in
plants
is
adequately
understood.
The
10/
8/
93
Residue
Chemistry
Chapter
reported
that
acceptable
metabolism
studies
had
been
conducted
on
alfalfa,
pineapple,
and
sugarcane.
These
studies
indicate
that
root
uptake
is
the
principal
mechanism
for
the
absorption
of
hexazinone
by
plants
from
soils.
Hexazinone
is
translocated
through
the
xylem
to
the
foliage
where
it
blocks
the
photosynthetic
process.
Hexazinone
is
metabolized
by
hydroxylation
to
metabolite
A
which
is
then
metabolized
to
metabolite
C
by
demethylation
and
to
metabolite
E
after
oxidation.
The
available
plant
metabolism
data
for
hexazinone
were
presented
to
the
HED
Metabolism
Assessment
Review
Committee
(MARC)
in
a
meeting
held
January
29,
2002
for
a
determination
of
hexazinone
residues
to
be
regulated
(DP
Barcode
D279897,
02/
05/
2002,
S.
Kinard).
The
Committee
concluded
that
the
hexazinone
tolerance
expression
for
plants
and
rotational
crops
should
include
hexazinone
and
metabolites
A,
B,
C,
D,
and
E.
Toxicity
data
for
the
metabolites
are
not
available
but
based
on
the
structural
similarity
of
the
metabolites
it
is
assumed
they
will
exhibit
similar
toxicity
to
the
parent
hexazinone.
The
current
tolerance
expression
for
hexazinone
in
40
CFR
§180.396
is
for
"combined
residues
of
the
herbicide
hexazinone
(3
cyclohexyl
6
(dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione)
and
its
metabolites,
calculated
as
hexazinone."
Hexazinone
metabolites
which
are
currently
regulated
(because
they
are
measured
by
the
enforcement
analytical
method)
include
the
parent
and
metabolites
A,
B,
C,
D,
and
E.
The
hexazinone
enforcement
method
involves
extraction
and
several
cleanup
steps,
followed
by
analysis
by
GLC
with
nitrogen
phosphorus
detection.
Hexazinone
and
each
of
the
five
metabolites
are
quantitated
as
individual
peaks.
The
chemical
names
and
structures
of
the
hexazinone
residues
of
concern
in
plants
and
livestock
are
presented
in
Figure
1.
Brief
summaries
of
the
available
plant
metabolism
data,
initially
reported
in
the
Hexazinone
Registration
Standard
dated
2/
82
and
then
in
the
Hexazinone
FRSTR
Residue
Chemistry
Chapter
dated
5/
25/
88,
are
presented
below.
Alfalfa
(MRID
00104846)
In
a
study
conducted
at
the
University
of
Kentucky
Research
Farm,
a
12
ft
2
area
of
alfalfa
was
isolated
and
fenced
for
this
study.
In
mid
March,
the
test
plot
was
sprayed
using
a
hand
held
sprayer,
with
125
mg
of
[
14
C]
hexazinone
dissolved
in
water;
the
application
rate
was
equivalent
to
1.0
lb
ai/
100
gal/
A.
Alfalfa
samples
were
collected
at
two,
three,
and
six
months
after
treatment.
Total
radioactive
residues
(TRR),
calculated
as
hexazinone,
declined
at
each
sampling
interval,
and
respectively
were
0.6,
0.5,
and
0.1
ppm.
The
extractable
percentages
of
TRR
were
95,
84,
and
80%
for
the
two,
three
and
six
month
harvests,
respectively.
Analysis
of
the
two
month
alfalfa
cutting
identified
hexazinone
(2.7%
TRR),
free
metabolite
A
(7.1%
TRR),
free
metabolite
B
13
N
N
N
O
O
CH
3
N
CH
3
CH
3
(0.7%
TRR),
and
conjugated
metabolites
A,
B,
and
C
(4.5%
TRR).
The
remaining
radioactive
residues
were
found
in
water
soluble,
polar
materials
which
were
subsequently
found
to
be
comprised
of
amino
acids,
sugars,
polybasic
acids,
and
smaller
amounts
of
natural
products.
Pineapple
(MRID
00126127)
A
pineapple
metabolism
study
was
submitted
by
the
basic
registrant
in
conjunction
with
PP#
3F2846.
The
Hexazinone
FRSTR
Residue
Chemistry
Chapter
dated
5/
25/
88
reported
the
salient
features
of
this
study
with
respect
to
residue
characterization/
identification
only.
The
fruit
(pulp
and
rind)
were
extracted
with
methanol,
and
94
99%
of
TRR
was
extractable.
The
following
components
were
identified
in
the
pulp:
hexazinone
(0.8
1.8%
TRR),
metabolite
A
(23
28%
TRR),
metabolite
C
(13
15%
TRR),
metabolite
D
(16
21%
TRR),
and
metabolite
F
(1
2%
TRR).
Sugarcane
(MRID
00078047)
Greenhouse
grown
dwarf
sugarcane
were
grown
in
large
tubs
(2
canes/
tub)
and
when
the
canes
reached
5.5
to
6.0
feet
in
height,
they
were
treated
with
a
soil
drench
application
of
[
14
C]
hexazinone
at
rates
of
0.54
and
1.0
kg/
ha
(0.48
and
0.89
lb
ai/
A);
a
third
tub
was
maintained
as
a
control.
About
six
months
after
treatment,
sugarcane
samples
were
collected.
The
TRRs,
calculated
as
hexazinone,
were
0.07
0.08
and
0.05
ppm
in
sugarcane
treated
at
0.89
and
0.48
lb
ai/
A,
respectively.
Following
organic
solvent
extraction,
76%
of
TRR
was
recovered.
The
following
components
were
identified
by
GC/
MS
in
sugarcane:
metabolite
E
(30%
TRR),
metabolite
C
(23%
TRR),
metabolite
A
(14%
TRR),
metabolite
B
(1%
TRR),
metabolite
D
(3%
TRR),
and
hexazinone
(<
1%
TRR).
Figure
1.
Chemical
Structures
of
Hexazinone
and
its
Regulated
Metabolites
(Metabolites
A
through
F).
Common
Name/
Code
Chemical
name
Structure
Hexazinone
3
cyclohexyl
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
Figure
A
(continued).
Common
Name/
Code
Chemical
name
Structure
14
(continued
next
page)
N
N
N
O
O
CH
3
N
CH
3
CH
3
HO
N
N
N
O
O
CH
3
N
H
CH
3
N
N
N
O
O
CH
3
N
H
CH
3
HO
N
N
NH
O
O
CH
3
O
Metabolite
A
3(
4
hydroxycyclohexyl)
6
(dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
Metabolite
A
1
is
hydroxylated
at
the
2
position
of
the
cyclohexyl
ring;
Metabolite
A
2
is
hydroxylated
at
the
3
position
of
the
cyclohexyl
ring.
Metabolite
B
3
cyclohexyl
6(
methylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
Metabolite
C
3(
4
hydroxycyclohexyl)
6
methylamino
1
methyl
1,3,5
triazine
2,4(
1H,
3H
dione
Metabolite
C
1
is
hydroxylated
at
the
2
position
of
the
cyclohexyl
ring;
Metabolite
C
2
is
hydroxylated
at
the
3
position
of
the
cyclohexyl
ring.
Metabolite
D
3
cyclohexyl
1
methyl
1,3,5
2,4,6
1H,
3H,
5H)
trione
Figure
A
(continued).
Common
Name/
Code
Chemical
name
Structure
15
N
N
NH
O
O
CH
3
O
HO
N
N
N
O
O
CH
3
NH
2
Metabolite
E
3(
4
hydroxycyclohexyl)
1
methyl
1,3,5
triazine
2,4,6(
1H,
3H,
5H)
trione
Metabolite
F
3
cyclohexyl
6
amino
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
16
GLN
860.1300:
Nature
of
the
Residue
Livestock
The
qualitative
nature
of
the
residue
in
livestock
is
adequately
understood
based
on
acceptable
ruminant
and
poultry
metabolism
studies.
The
requirement
to
confirm
the
identities
of
metabolites
in
goat
tissues
and
milk
by
a
second
method,
specified
in
the
10/
8/
93
Residue
Chemistry
Chapter,
has
been
fulfilled.
The
requirement
to
radiovalidate
the
proposed
enforcement
method
using
samples
collected
from
the
ruminant
metabolism
study
has
also
been
fulfilled.
No
additional
livestock
metabolism
data
are
required
for
reregistration.
The
available
livestock
metabolism
data
were
presented
to
the
HED
MARC
in
a
meeting
held
January
29,
2002
for
a
determination
of
hexazinone
residues
to
be
regulated
(D279897,
02/
05/
2002,
S.
Kinard).
The
Committee
concluded
that
the
hexazinone
tolerance
expression
for
ruminants
should
include
hexazinone
plus
metabolites
B,
C,
C
2,
and
F
for
milk.
The
Committee
concluded
that
the
hexazinone
tolerance
expression
for
ruminant
tissue
should
include
hexazinone
plus
metabolites
B
and
F.
The
Committee
concluded
that
residues
of
hexazinone
and
metabolites
B,
C,
C1
C
2,
and
F
should
be
taken
into
account
when
risk
assessments
are
done.
The
above
determination
was
partially
based
on
the
assumption
that
the
current
enforcement
method
listed
in
the
PAM,
Volume
II
for
plant
commodities
could
be
used
for
livestock
commodities
provided
additional
method
validation
data
are
submitted;
there
is
presently
no
enforcement
method
listed
in
PAM
Volume
II
for
livestock
commodities.
HED
has
determined
that
tolerances
for
hexazinone
residues
in
eggs
and
poultry
tissues
are
not
required
(Category
3,
40
CFR
§180.6a)
based
on
the
results
of
the
reviewed
poultry
metabolism
study.
In
the
poultry
study,
the
liver
contained
the
highest
TRR,
0.19
ppm.
Considering
that
the
feeding
level
was
about
38x
the
maximum
theoretical
dietary
burden,
the
maximum
residue
in
poultry
tissue
would
be
0.005
ppm,
an
order
of
magnitude
below
the
limit
of
detection
for
hexazinone
metabolites.
Brief
summaries
of
available
goat
and
hen
metabolism
studies
are
presented
below.
Goat
(MRIDs
42187901,
43074201,
and
43488901)
A
lactating
goat
was
dosed
orally
with
[
14
C]
hexazinone
radiolabeled
in
the
triazine
ring
at
a
dose
rate
of
136.4
mg/
day,
equivalent
to
2.2
mg/
kg
body
weight
for
five
consecutive
days.
This
dose
represents
a
level
of
approximately
90
ppm
in
the
feed,
which
is
19.4x
the
maximum
theoretical
dietary
burden
for
ruminants.
TRRs,
expressed
as
hexazinone
equivalents,
were
6.74
ppm
in
milk,
3.03
ppm
in
liver,
2.54
ppm
in
kidney,
0.27
ppm
in
muscle,
and
0.03
ppm
in
fat.
Residues
were
adequately
extracted
with
organic
solvents.
A
list
of
characterized/
identified
residues
in
goat
matrices
is
presented
below.
17
Table
1.
Characterization/
identification
of
residues
from
goat
milk
and
tissues
dosed
with
90
ppm
of
[
14
C]
hexazinone
for
5
consecutive
days.
(Reproduced
from
DP
Barcode
D198348,
5/
25/
94,
S.
Hummel).
Metabolite
Liver
TRR
=
3.03
ppm
Kidney
TRR
=
2.54
ppm
Muscle
TRR
=
0.27
ppm
Milk
TRR
=
6.74
ppm
%TRR
PPM
%TRR
PPM
%TRR
PPM
%TRR
PPM
Hexazinone
0.1
0.
04
<0.01
<0.01
1.
2
0.08
B
56.7
1.
70
28.3
0.
72
40.7
0.
11
48.1
3.
24
A
2
<0.01
0.4
0.
01
<0.01
0.4
0.
03
A,
A
1
0.
1
0.04
2.0
0.
05
<0.01
3.9
0.
26
C
<0.01
3.1
0.
08
<0.01
3.4
0.
23
C
1,
C
2
11.9
0.
36
18.5
0.
47
7.
4
0.02
16.6
1.
12
E
<0.01
1.2
0.
03
<0.01
<0.01
F
11.6
0.
35
37.4
0.
95
25.9
0.
07
17.1
1.
15
Others*
5.
8
0.19
5.1
0.
13
14.8
0.
04
4.
0
0.27
Total
Identified
86.2
2.
68
96.0
2.
44
88.9
0.
24
94.7
6.
38
Unknown
<0.01
<0.01
<0.01
5.2
0.
35
Unextracted
11.9
0.
36
4.
7
0.12
11.1
0.03
0.1
0.
01
Total
98.1
3.
03
101
2.56
100
0.27
100
6.74
*Others
identified
at
<0.01
ppm
each
Poultry
(MRIDs
41524801,
42690601,
43074201)
Five
ISA
Brown
laying
hens
were
dosed
orally
at
6.9
mg/
day
with
carbonyl
labeled
[
14
C]
hexazinone
for
six
consecutive
days.
The
daily
dose
rate
was
equivalent
to
57
ppm
in
the
feed,
which
is
38x
the
maximum
theoretical
dietary
burden.
Mean
TRR
levels,
expressed
as
hexazinone
equivalents,
were
0.189
ppm
in
liver,
0.02
ppm
in
fat,
0.078
and
0.106
ppm
in
thigh
and
breast
muscle,
respectively,
and
0.059
ppm
in
skin.
TRR
level
in
eggs
(day
6)
was
0.12
ppm.
Residues
were
adequately
extracted
with
organic
solvents.
No
single
metabolite
in
edible
poultry
tissue
was
greater
than
0.04
ppm,
and
unidentified
metabolites
represented
less
than
0.05
ppm
in
all
edible
tissues.
A
list
of
characterized
and
identified
residues
in
poultry
muscle
and
eggs
is
presented
below.
18
Table
2.
Characterization/
identification
of
residues
from
hen
eggs
and
muscle
tissues
dosed
with
57
ppm
of
[
14
C]
hexazinone
for
six
consecutive
days.
(DP
Barcode
D198348,
5/
25/
94,
S.
Hummel).
Metabolite
Muscle
TRR
=
0.12
ppm
Eggs
TRR
=
0.13
ppm
%TRR
PPM
%TRR
PPM
Hexazinone
–
<0.01
<0.01
A,
A
1,
A
2
16.7
0.
02
23.1
0.
03
C
16.7
0.02
23.1
0.
03
A
OH,
C
OH
16.7
0.
02
7.
7
0.01
E
<0.01
<0.01
Others*
33.3
0.
04
15.4
0.
02
Total
Identified
83.5
0.
10
69.3
0.
09
Unknown
16.7
0.
02
23.1
0.
03
Unextracted
8.4
0.01
7.7
0.
01
Total
109
0.13
100
0.13
*Others
identified
at
<0.01
ppm.
GLN
860.1340:
Residue
Analytical
Methods
Plant
Commodities
The
10/
8/
93
Residue
Chapter
concluded
that
adequate
methods
are
available
for
purposes
of
data
collection
and
enforcement
of
tolerances
for
residues
of
hexazinone
and
metabolites
A,
B,
C,
D,
and
E
in/
on
plant
commodities.
No
additional
data
on
residue
analytical
methods
for
plant
commodities
are
required
for
reregistration.
For
tolerance
enforcement,
the
PAM,
Volume
II
lists
Method
I
as
available
for
the
determination
of
hexazinone
residues
of
concern
in/
on
plant
commodities.
Using
this
method,
residues
of
hexazinone
and
metabolites
A,
B,
D,
and
E
are
extracted
with
chloroform
and
cleaned
up
by
liquid
liquid
partitioning.
Residues
of
Metabolite
C,
a
highly
polar
metabolite,
are
extracted
from
samples
with
methanol
in
a
separate
isolation
scheme.
Both
schemes
use
derivatization
of
residues
with
trifluoroacetic
anhydride
and
determination
of
the
derivatives
by
nitrogen
selective
GLC.
Some
samples
(e.
g.,
alfalfa
and
grasses)
require
additional
cleanup
on
a
gel
permeation
column,
before
derivatization,
or
on
a
deactivated
Florisil
column,
either
before
or
after
derivatization.
The
combined
limit
of
quantitation
(LOQ)
for
hexazinone
residues
by
Method
I
in
PAM,
Volume
II,
is
0.55
ppm.
For
data
collection,
the
registrant
utilized
Method
Nos.
92013
V2
and
92013
V3
during
analyses
of
samples
collected
from
field
trials
on
alfalfa.
These
methods
are
similar
to
the
PAM,
Volume
II
method
but
were
modified
to
include
additional
clean
up
steps.
They
have
been
deemed
adequate
for
data
collection
based
on
acceptable
method
19
validation
and
concurrent
recovery
data.
Livestock
Commodities
The
10/
8/
93
Residue
Chapter
required
data
collection
and
tolerance
enforcement
methodology
for
determination
of
hexazinone
residues
of
concern
in
livestock
commodities.
In
an
attempt
to
fulfill
this
requirement,
the
registrant
requested
a
meeting
with
HED
to
report
progress
of
their
work
in
developing
a
new
method
prior
to
submitting
it
for
an
independent
laboratory
validation
(ILV).
In
a
meeting
held
8/
31/
94,
the
registrant
advised
that
the
current
method
in
PAM,
Volume
II
for
plant
commodities
did
not
appear
appropriate
for
livestock
commodities
because
of
complications
with
matrix
effects
and
the
inability
to
detect
metabolite
F,
among
other
problems.
The
registrant
instead
proposed
an
LC/
MS
method
(designated
as
du
Pont
AMR
3783
96)
as
an
enforcement
method.
The
proposed
method
would
determine
residues
of
parent
hexazinone,
metabolite
B,
metabolite
C
and
its
isomer
(C
2),
and
metabolite
F
in
milk.
In
livestock
tissues,
Method
AMR
3783
96
would
determine
residues
of
parent
hexazinone,
metabolite
B,
and
metabolite
F.
Briefly,
residues
in
milk
and
animal
tissues
are
extracted
three
times
with
acetone:
aqueous
0.1
M
potassium
phosphate/
0.5
M
sodium
chloride
solution
(1:
1,
v:
v).
The
extract
is
concentrated
to
remove
the
acetone,
and
purified
using
solid
phase
extraction
(SPE)
cartridges.
A
combination
of
reverse
(C8)
and
normal
(silica)
phase
SPE
sorbents
is
used
to
remove
most
substances
that
may
interfere
with
the
instrument
analysis.
Residues
of
hexazinone
and
metabolites
B
and
F
are
quantitated
in
tissue
samples
and
residues
of
hexazinone
and
metabolites
B,
C,
C
2,
and
F
are
quantitated
in
milk
using
LC/
MS
with
an
electrospray
interface
and
selected
ion
monitoring
(SIM).
The
reported
LOQs
were
0.02
ppm
for
hexazinone
and
metabolite
B
and
0.05
ppm
for
metabolites
C,
C
2,
and
F.
The
proposal
to
develop
DuPont
Method
AMR
3783
96
as
an
enforcement
method
was
based
on
a
cattle
feeding
study
which
had
been
reviewed
by
HED
and
deemed
acceptable.
Data
from
the
cattle
feeding
study
indicate
that
in
milk,
the
metabolites
determined
by
the
proposed
method
represent
nearly
95%
of
total
hexazinone
residues.
In
tissues,
parent
and
metabolite
B
represent
at
least
85%
of
total
residues
in
liver
and
63%
of
total
residues
in
kidney;
metabolite
B
is
the
only
residue
detected
in
muscle,
even
at
the
10x
feeding
level;
and
all
residues
are
nondetectable
in
fat
at
the
10x
level.
DuPont
Method
AMR
3783
96
has
been
subjected
to
a
successful
ILV
and
a
radiovalidation
study.
The
ILV
data
did
support
the
reliability
of
and
reproducibility
of
the
method
for
the
determination
of
residues
of
hexazinone,
metabolite
B,
metabolite
C
and
its
isomer
(C
2),
and
metabolite
F
in
milk;
the
ILV
data
also
showed
that
Method
AMR
3783
96
can
adequately
recover
residues
of
hexazinone,
metabolite
B,
and
metabolite
F
in
livestock
tissues.
Method
AMR
3783
96
will
be
forwarded
to
the
Analytical
Chemistry
Branch
(ACL;
Beltsville,
MD)
for
a
tolerance
method
validation
20
by
Agency
chemists.
If
the
results
of
method
validation
by
Agency
chemists
are
successful,
then
Method
AMR
3783
96
will
be
proposed
for
inclusion
in
PAM,
Volume
II,
and
no
additional
data
concerning
this
GLN
topic
will
be
required
for
reregistration.
GLN
860.1360:
Multiresidue
Methods
The
reregistration
requirements
for
multiresidue
methods
data
are
fulfilled.
The
10/
99
FDA
PESTDATA
database
(PAM,
Volume
I,
Appendix
I)
indicates
that
hexazinone
is
only
partially
recovered
(50
80%)
using
Multiresidue
Method
Sections
302
(Luke
Method;
Protocol
D)
and
is
not
recovered
using
Sections
303
(Mills,
Onley,
Gaither;
Protocol
E
nonfatty
foods)
and
304
(Mills;
Protocol
E
fatty
foods).
There
is
a
small
recovery
(<
50%)
of
metabolite
A
(IN
T3937)
and
metabolite
C
INT3935
using
Multiresidue
Method
Section
302
(Luke
Method;
Protocol
D).
There
is
also
a
small
recovery
(<
50%)
of
metabolite
B
(IN
T3928)
and
metabolite
E
(IN
T3936)
using
Multiresidue
Method
Section
302
(Luke
Method;
Protocol
D)
but
the
metabolites
are
not
recovered
using
Sections
303
(Mills,
Onley,
Gaither;
Protocol
E
nonfatty
foods)
and
304
(Mills;
Protocol
E
fatty
foods).
Metabolite
D
(IN
B2838)
is
partially
recovered
(50
80%)
using
Multiresidue
Method
Sections
302
(Luke
Method;
Protocol
D)
and
is
not
recovered
using
Sections
303
(Mills,
Onley,
Gaither;
Protocol
E
nonfatty
foods)
and
304
(Mills;
Protocol
E
fatty
foods).
GLN
860.1380:
Storage
Stability
Data
Plant
Commodities
The
Updated
Table
A
for
Residue
Chemistry
RED
Chapter
dated
9/
8/
94
required
additional
storage
stability
data
for:
(1)
hexazinone
and
metabolites
in
alfalfa,
and
(2)
metabolite
C
in
grass.
The
registrant
has
submitted
the
requested
data
which
were
deemed
adequate
to
support
the
storage
conditions
and
intervals
of
samples
used
for
tolerance
reassessment.
No
additional
storage
stability
data
for
plant
and
processed
commodities
are
required
for
reregistration.
A
summary
of
the
available
storage
stability
data
is
presented
below.
Residues
of
hexazinone
and
its
metabolites
A,
B,
C,
D,
and
E
are
relatively
stable
under
frozen
(
20
to
10
°C)
storage
conditions
in/
on
blueberries
for
up
to
13
months,
in/
on
pineapple
for
up
to
8
months,
in
pineapple
juice
for
up
to
6
months,
in/
on
sugarcane
for
up
to
12
months,
and
in
sugarcane
processed
commodities
for
up
to
6
months.
Hexazinone
and
metabolites
A,
B,
D,
and
E
are
also
stable
in
grass
samples
during
frozen
(
20
°C)
storage
for
up
to
24
months,
and
metabolite
C
is
stable
in
grass
samples
during
frozen
(
20
±
10
°C)
storage
for
up
to
36
months.
Livestock
Commodities
21
Adequate
storage
stability
data
are
available
to
support
the
existing
ruminant
feeding
study.
Samples
of
milk,
liver,
kidney,
muscle,
and
fat
samples
were
stored
under
freezer
storage
conditions
for
maximums
of
8,
10,
14,
2,
and
2
months,
respectively,
prior
to
residue
analysis.
In
a
fortification
study,
hexazinone
residues
of
concern
were
found
to
be
stable
during
maximum
storage
times
for
samples
collected
and
analyzed
from
the
feeding
study.
GLN
860.1500:
Crop
Field
Trials
Pending
label
revisions
for
certain
crops,
the
reregistration
requirements
for
data
depicting
magnitude
of
the
residue
in/
on
the
following
raw
agricultural
commodities
(RACs)
are
satisfied:
alfalfa
forage,
alfalfa
hay,
alfalfa
seed,
blueberries,
pineapple,
and
sugarcane.
An
adequate
number
of
field
trials
have
been
conducted
for
these
RACs,
and
the
trials
were
conducted
using
registered
hexazinone
formulation(
s)
at
the
maximum
registered
rate.
Brief
summaries
of
available
hexazinone
residue
data,
deemed
useful
for
tolerance
reassessment,
are
presented
below.
It
is
noted
that
product
labels
of
registrants
other
than
du
Pont
were
not
examined
in
the
preparation
of
this
document.
Berries
Group
Blueberry
The
10/
8/
93
Residue
Chapter
concluded
that
no
additional
data
are
required
for
blueberries
provided
all
pertinent
product
labels
are
amended
to
specify
PHIs
of
90
and
450
days
for
application
to
highbush
and
lowbush
blueberries,
respectively.
Data
(MRIDs
41964101
and
41964102)
reviewed
in
the
Hexazinone
Update
indicate
that
the
combined
residues
of
hexazinone
and
its
regulated
metabolites,
as
measured
by
the
data
collection
method,
were
<0.3
ppm
(nondetectable;
<0.05
ppm
for
each
compound)
in/
on:
(1)
12
samples
of
lowbush
blueberries
harvested
433
446
days
following
a
single
application
of
the
2
lb/
gal
EC
or
90%
SC
formulation
at
3
or
6
lb
ai/
A
(1.5
or
3.0x
the
maximum
registered
rate)
using
ground
or
aerial
equipment;
and
(2)
12
samples
of
highbush
blueberries
harvested
68
97
days
following
a
single
application
of
the
2
lb/
gal
EC
or
90%
SC
formulation
at
2
or
4
lb
ai/
A
(0.8
or
1.3x
the
maximum
registered
rate).
Based
on
the
combined
LOQs
(0.55
ppm)
of
the
enforcement
method,
HED
is
now
recommending
that
the
RAC
tolerance
be
reassessed
from
0.2
ppm
to
0.60
ppm.
Although
uses
of
hexazinone
on
blueberries
(see
Table
A2)
are
limited
to
Section
24(
c)
registration,
label
revisions
remain
a
requirement.
The
product
labels
for
ME980002
22
and
ME980003,
which
are
limited
for
use
on
lowbush
blueberries,
should
be
amended
to
specify
a
PHI
of
450
days.
The
product
label
for
NC830012
should
also
be
amended
to
specify
PHIs
of
90
and
450
days
for
application
to
highbush
and
lowbush
blueberries,
respectively.
Grass
Forage,
Fodder,
and
Hay
Group
Grass
(pasture
and
rangeland)
forage
An
examination
of
registered
uses
of
hexazinone
on
pasture
and
rangeland
grasses
(see
Table
A2)
reveal
that
there
two
distinct
use
patterns,
a
basal
soil
application
and
a
broadcast
application.
It
is
noted
that
the
10
ppm
tolerance
for
grass
forage
(listed
as
"grasses,
pasture"
and
"grasses,
range"
under
40
CFR
§180.396)
was
established
based
on
residue
data
reflecting
basal
soil
application
only.
Data
reflecting
basal
soil
application
were
submitted
under
PP#
1F2513
and
summarized
in
the
Hexazinone
FRSTR
Residue
Chemistry
Chapter
dated
5/
25/
88.
Samples
of
range
and
pasture
grasses
were
harvested
at
various
intervals
following
application
of
the
2
lb/
gal
EC
formulation
at
3
or
6
mL
per
one
inch
of
diameter
at
breast
height
(0.75
or
1.5x
the
maximum
registered
rate
for
directed
spray
basal
soil
application).
Samples
were
taken
2",
12",
and
24"
in
radius
from
the
treatment
point
on
days
0
56
after
application.
The
FRSTR
Residue
Chemistry
Chapter
did
not
report
specific
residues;
however,
it
was
concluded
that
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone)
did
not
exceed
the
established
tolerances
of
10
ppm
in/
on
treated
samples
of
pasture
and
range
grass
forage.
In
the
absence
of
residue
data
reflecting
broadcast
application,
HED
is
requiring
the
following
additional
data
for
grass
forage
before
the
RAC
tolerance
can
be
reassessed:
"Data
depicting
magnitude
of
the
residues
of
hexazinone
and
metabolites
A,
B,
C,
D,
and
E
in/
on
grass
forage
harvested
0
day
following
a
single
broadcast
application
of
representative
formulations
at
1.125
lb
ai/
A.
It
is
the
Agency
policy
to
require
0
day
crop
field
residue
data
for
grass
forage
unless
it
is
not
feasible
(e.
g.,
preplant/
preemergence
pesticide
uses).
The
formulations
to
be
tested
may
be
applied
in
side
by
side
plots.
The
location
and
number
of
trial
should
be
in
compliance
with
the
current
OPPTS
GLN
for
adequate
geographic
representation
of
data.
Grass
(pasture
and
rangeland)
hay
The
reregistration
requirements
for
residue
data
on
grass
hay
have
not
been
fulfilled.
The
registrant
has
submitted
a
petition
(PP#
1F3967)
for
the
establishment
of
a
tolerance
for
residues
of
hexazinone
and
its
metabolites
in/
on
grass
hay.
The
petition
is
currently
in
reject
status
because
additional
grass
hay
data,
from
field
trials
with
adequate
23
geographical
representation,
remain
outstanding.
Since
1991
HED
has
reviewed
two
proposals
to
amend
the
original
petition
requesting
that
the
Agency
establish
tolerances
for
grass
hay
based
on
theoretical
grass
drying
factors.
HED
recommended
against
the
establishment
of
grass
hay
tolerances
each
time.
In
addition,
HED
reviewed
two
registrant
responses
to
the
petition
amendment
reviews
and
concluded
in
each
case
that
the
recommendation
to
require
actual
field
trial
data
for
grass
hay
is
appropriate
(D162863,
D181318,
D172408,
D201738).
Non
Grass
Animal
Feeds
(Forage,
Fodder,
Straw,
and
Hay)
Group
Alfalfa
forage
and
hay
The
Updated
Table
A
for
Residue
Chemistry
RED
Chapter
dated
9/
8/
94
concluded
that
adequate
residue
data
are
available
for
alfalfa
forage
and
hay.
However,
label
amendments
were
required
on
all
product
labels
for
alfalfa,
including
supplemental
labels,
to
establish
a
30
day
PHI
for
the
feeding
of
forage
and
the
cutting
of
hay.
The
available
residue
data
(MRIDs
43074401
and
43074402)
indicate
that
the
combined
residues
of
hexazinone
and
its
metabolites
A,
B,
C,
D,
and
E
did
not
exceed
the
established
tolerances
of
2.0
ppm
in/
on
alfalfa
forage
and
8.0
ppm
in/
on
alfalfa
hay
harvested
29
31
days
following
a
single
broadcast
dormant
or
non
dormant
application
of
the
2
lb/
gal
EC
or
90%
SC
formulation
at
1.5
lb
ai/
A
(~
1x).
The
maximum
combined
residues
in/
on
treated
samples
were
<1.87
ppm
and
<3.33
ppm
for
alfalfa
forage
and
hay,
respectively.
Based
on
these
data,
the
established
tolerance
for
alfalfa
forage
is
reassessed
at
its
existing
level
of
2.0
ppm;
however,
the
tolerance
for
alfalfa
hay
should
be
lowered
from
8.0
ppm
to
4.0
ppm.
Table
A2
shows
that
product
labels
for
the
90%
SC
(EPA
Reg.
No.
352
378)
and
75%
DF
(EPA
Reg.
No.
352
58)
formulations
have
been
revised
in
compliance
with
the
requested
label
amendment.
However,
the
product
label
for
the
2
lb/
gal
EC
(EPA
Reg.
No.
352
392)
formulation
does
not
specify
any
PHI;
this
label
must
be
amended
to
establish
a
30
day
PHI
(or
pregrazing
interval)
for
the
feeding
of
forage
and
the
cutting
of
hay.
Alfalfa
seed
The
Updated
Table
A
for
the
Residue
Chemistry
RED
Chapter
dated
9/
8/
94
concluded
that
adequate
residue
data
have
been
submitted
for
alfalfa
seed;
the
Chapter,
however,
required
the
registrant
to
propose
a
tolerance
for
this
commodity
in
order
to
support
registered
uses
of
hexazinone
on
alfalfa
grown
for
seed.
The
available
residue
data
(MRIDs
43074401
and
43074402)
indicate
that
the
combined
residues
of
hexazinone
and
its
regulated
metabolites
ranged
from
<1.30
ppm
24
(sum
of
the
LOQs)
to
<1.46
ppm
in/
on
alfalfa
seed
following
a
single
broadcast
dormant
application
of
the
2
lb/
gal
EC
or
90%
SC
formulation
at
0.75
lb
ai/
A
(1.5x
the
maximum
registered
rate
on
alfalfa
grown
for
seed);
no
data
were
submitted
reflecting
1.0x.
HED
is
requesting
the
registrant
to
propose
a
tolerance
for
hexazinone
residues
of
concern
in/
on
alfalfa
seed;
the
available
data
suggest
that
a
tolerance
level
of
2.0
ppm
is
appropriate.
Residue
data
and
a
tolerance
proposal
for
alfalfa
seed
screenings,
previously
requested
in
the
Updated
Table
A
for
the
Residue
Chemistry
RED
Chapter
dated
9/
8/
94,
are
no
longer
required
because
this
item
has
been
deleted
from
Table
1
of
OPPTS
860.1000
as
a
significant
livestock
feed
item.
Miscellaneous
Commodities
Pineapple
The
10/
8/
93
Residue
Chapter
concluded
that
no
additional
residue
data
are
required
for
pineapple
provided
all
pertinent
product
labels
are
amended
to
specify
a
maximum
application
rate
of
3.6
lb
ai/
A/
cropping
cycle
and
a
minimum
PHI
of
181
days.
The
basic
registrant
has
complied
with
this
requirement
as
shown
in
Table
A2.
The
available
data
(MRID
42535601)
indicate
that
the
combined
residues
of
hexazinone
and
its
regulated
metabolites,
as
measured
by
the
data
collection
method,
were
<0.35
ppm
(or
<0.05
ppm
for
each
compound)
in/
on
pineapple
fruits
harvested
at
a
minimum
PHI
of
181
days
following
five
ground
applications
of
a
representative
hexazinone
formulation
at
0.45
0.9
lb
ai/
A
for
a
total
rate
of
3.6
lb
ai/
A.
Based
on
the
combined
LOQs
(0.55
ppm)
of
the
enforcement
method,
HED
is
now
recommending
that
the
RAC
tolerance
be
reassessed
from
0.5
ppm
to
0.60
ppm.
HED's
request
to
impose
a
feeding
restriction
on
pineapple
forage,
previously
specified
in
the
Updated
Table
A
for
the
Residue
Chemistry
RED
Chapter
dated
9/
8/
94,
is
no
longer
required
because
this
item
has
been
deleted
from
Table
1
of
OPPTS
860.1000
as
a
significant
livestock
feed
item.
Sugarcane
The
Updated
Table
A
for
Residue
Chemistry
RED
Chapter
dated
9/
8/
94
concluded
that
no
additional
residue
data
are
required
for
sugarcane
provided
all
pertinent
product
labels
are
amended
to
prohibit
use
of
hexazinone
on
sugarcane
grown
in
FL.
The
basic
registrant
has
complied
with
the
requested
label
amendment
(see
Table
A2).
Presently,
registered
uses
of
hexazinone
on
sugarcane
are
limited
to
those
grown
in
the
states
of
HI,
LA,
TX,
and
in
Puerto
Rico.
25
The
available
data
(MRID
42322701)
indicate
that
the
combined
residues
of
hexazinone
and
its
regulated
metabolites,
as
measured
by
the
data
collection
method,
were
<0.35
(or
<0.05
ppm
for
each
compound)
in/
on
samples
of
sugarcane
treated
with
the
90%
SC
formulation
of
hexazinone
from
the
following
test
locations:
(i)
in
Puerto
Rico
where
sugarcane
was
harvested
288
days
following
a
single
postemergence
application
at
0.45
lb
ai/
A
(0.5x
the
maximum
registered
seasonal
rate
for
this
area);
(ii)
in
TX
where
sugarcane
was
harvested
234
days
following
one
preemergence
application
followed
by
one
postemergence
application
at
0.675
lb
ai/
A/
application
(0.75x
the
maximum
seasonal
rate
in
TX);
and
(iii)
in
HI
where
sugarcane
was
harvested
179
181
days
following
a
total
of
four
applications
(one
preemergence
application
at
1.35
or
1.47
lb
ai/
A,
a
postemergence
application
at
0.45
lb
ai/
A/
application,
followed
by
two
postemergence
applications
at
1.8
lb
ai/
A/
application)
for
a
total
rate
of
5.4
5.5
lb
ai/
A/
season
(1.5x
the
maximum
seasonal
rate
in
HI).
Based
on
the
combined
LOQs
(0.55
ppm)
of
the
enforcement
method,
HED
is
now
recommending
that
the
RAC
tolerance
be
reassessed
from
0.20
ppm
to
0.60
ppm.
GLN
860.1520:
Processed
Food/
Feed
Pineapple
process
residue
and
juice
The
registrant
has
submitted
a
pineapple
processing
study
(MRIDs
42492101
and
43401901)
which
was
first
deemed
inadequate
but
later
upgraded
as
acceptable.
Residues
of
hexazinone
and
its
regulated
metabolites
did
not
concentrate
in
pineapple
process
residue
and
juice
except
for
Metabolite
B
in
process
residue.
The
registrant
calculated
a
concentration
factor
of
3.0x
for
Metabolite
B
in
pineapple
process
residue
based
on
quantified
residues
of
0.06
ppm
in
pineapple
process
residue
and
0.02
ppm
in/
on
pineapple
RAC
after
treatment
with
hexazinone
at
a
1.0x
rate.
When
this
concentration
factor
of
3.0
x
is
multiplied
by
the
highest
average
field
trial
(HAFT)
residue
of
<0.05
ppm,
the
maximum
expected
residues
of
metabolite
B
in
pineapple
process
residue
is
0.15
ppm
which
is
less
than
the
reassessed
RAC
tolerance
of
0.60
ppm.
Therefore,
no
tolerance
for
pineapple
process
residues
is
warranted.
Sugarcane
molasses
and
refined
sugar
An
acceptable
sugarcane
processing
study
(MRIDs
42276001
and
42417901)
is
available.
The
reviewed
study
indicate
that
residues
of
the
parent
hexazinone
were
0.23
ppm
in/
on
the
RAC
(sugarcane)
following
application
of
the
90%
SC
formulation
at
a
total
rate
of
7.2
lb
ai/
A
(2.0x
the
maximum
seasonal
application
rate
for
sugarcane
grown
in
HI).
Residues
of
metabolites
A,
B,
C,
D,
and
E
were
each
nondetectable
(<
0.05
ppm)
in/
on
treated
RAC
samples.
Following
processing
of
the
RAC
according
to
simulated
commercial
practices,
residues
of
hexazinone
and/
or
metabolites
A
through
E
concentrated
in
bagasse
(1.6x)
and
"A
molasses"
(4.0x).
However,
residues
26
declined
in
raw
sugar
(reduction
factor
of
0.2x)
and
processed
sugar
(reduction
factor
of
0.2x).
The
presently
regulated
processed
commodities
of
sugarcane
are
molasses
and
refined
sugar;
bagasse
has
been
removed
from
Table
1
of
OPPTS
860.1000.
Samples
of
treated
"A
molasses"
from
the
above
study
were
re
analyzed
to
confirm
results.
The
average
total
residues
of
hexazinone
and
its
regulated
metabolites,
from
duplicate
analysis,
were
1.915
ppm
for
"A
molasses".
Based
on
this
re
analysis,
residues
of
hexazinone
and
metabolites
concentrated
about
8.0x
in
"A
molasses".
The
registrant
reported
that
a
4.0x
concentration
factor
should
be
considered
when
"A
molasses"
is
further
processed
to
final
(blackstrap)
molasses,
the
form
of
molasses
typically
fed
to
livestock.
To
reassess
the
adequacy
of
the
established
0.5
ppm
tolerance
for
sugarcane
molasses,
HED
will
consider
the
HAFT
residue
reported
from
the
field
study
as
well
as
the
concentration
factors
observed
from
the
processing
study.
Data
from
the
sugarcane
field
trials
indicate
that
residues
of
hexazinone
and
its
regulated
metabolites,
as
measured
by
the
data
collection
method,
were
<0.35
ppm
(or
<0.05
ppm
for
each
compound)
in/
on
samples
of
sugarcane
treated
according
to
the
maximum
registered
use
pattern.
According
to
OPPTS
GDLN
860.1520,
if
no
quantifiable
residues
are
found
in
the
RAC
from
the
maximum
registered
rate,
but
the
exaggerated
rate
does
produce
quantifiable
residues,
the
latter
samples
should
be
adjusted
for
the
degree
of
exaggeration.
These
adjusted
residues
should
then
be
compared
to
the
LOQ
for
the
RAC.
If
the
adjusted
residues
are
greater
than
or
equal
to
twice
the
LOQ,
then
a
tolerance
is
needed.
The
maximum
average
combined
residue
of
hexazinone
and
its
regulated
metabolites
was
1.915
ppm
for
"A
molasses".
To
correct
concentrations
in
"A
molasses"
to
blackstrap
molasses,
residues
in
"A
molasses"
are
multiplied
by
a
concentration
factor
of
4.0x,
resulting
in
7.66
ppm.
Adjusting
for
the
degree
of
exaggeration
(2.0x)
used
in
the
processing
study,
the
residue
for
blackstrap
molasses
is
3.83
ppm.
Because
this
result
is
greater
than
twice
the
LOQ
for
the
RAC
(sugarcane),
the
available
data
suggest
that
the
established
tolerance
for
sugarcane
molasses
should
be
decreased
from
5.0
ppm
to
4.0
ppm.
GLN
860.1480:
Meat,
Milk,
Poultry,
and
Eggs
The
Agency
changed
the
data
requirement
status
for
this
GLN
topic
from
"Reserved"
to
"Required"
because
the
results
of
ruminant
metabolism
study
suggested
a
very
significant
transfer
of
hexazinone
residues
of
concern
to
meat
and
milk
(Memo,
2/
4/
93,
R.
Perfetti).
The
registrant
has
since
submitted
an
acceptable
dairy
cattle
feeding
study
(MRID
43703501)
which
was
deemed
acceptable.
HED
is
recommending
that
in
order
to
reassess
the
established
hexazinone
tolerances
for
milk
and
the
fat,
meat,
and
meat
byproducts
of
livestock
and
to
compute
a
maximum
theoretical
dietary
burden
(MTDB)
27
of
hexazinone
to
livestock,
uses
on
pasture
and
rangeland
grasses
must
be
revoked.
A
MTDB
could
not
be
calculated
including
grass
and
grass
hay
since
additional
residue
data
are
required
for
use
patterns
in
which
significant
residues
are
expected
in/
on
the
RACs.
HED
recognizes
that
the
estimated
100,000
acres
of
pasture
and
rangeland
treated
with
hexazinone
is
relatively
low.
Since
grass
and
grass
hay
are
considered
major
dietary
components
of
ruminants
(up
to
60%
of
the
diet
per
current
OPPTS
GLN)
a
MTDB
for
livestock
could
not
be
developed
when
grasses
are
included
in
the
registered
uses.
HED
has
determined
that
a
MTDB
could
be
constructed
from
other
potential
feed
items
for
livestock
and
subsequently
tolerances
for
meats
and
milk
can
be
reassessed.
HED
has
previously
determined
that
tolerances
in
poultry
commodities
and
a
poultry
feeding
study
are
not
required
for
reregistration
based
on
results
of
reviewed
poultry
metabolism
data.
Maximum
theoretical
dietary
burden
(tentative,
pending
revocation
of
uses
on
pasture
and
rangeland
grasses
and
hay)
There
are
no
registered
direct
livestock
treatments
for
hexazinone
on
cattle,
goats,
hogs,
horses,
or
sheep.
However,
hexazinone
residues
of
concern
may
transfer
to
milk
and
edible
tissues
of
livestock
as
a
result
of
ingestion
of
feed
items
such
as:
alfalfa
forage,
hay,
meal,
and
silage;
grass
forage,
hay,
and
silage;
pineapple
process
residue;
and
sugarcane
molasses.
The
maximum
theoretical
dietary
burdens
of
hexazinone
to
beef
and
dairy
cattle
are
tentatively
calculated
to
be
4.64
ppm
(see
Table
3
below).
The
dietary
burden
calculations
are
tentative
because
it
assumes
use
on
pasture
and
rangland
grasses
will
be
canceled
and
tolerances
revoked
Table
3.
Tentative
calculation
of
maximum
ruminant
dietary
burden
for
hexazinone.
Feed
Commodity
Reassessed
Tolerance
(ppm)
%
Dry
Matter
1
Beef
Cattle
Dairy
Cattle
%
of
Diet
1
Burden
(ppm)
2
%
of
Diet
1
Burden
(ppm)
2
Alfalfa,
forage
2
35
60
3.
43
60
3.
43
Alfalfa,
hay
(as
meal)
4
89
15
0.68
15
0.68
Sugarcane
molasses
4
75
10
0.53
10
0.53
TOTAL
85
3
4.64
85
3
4.64
1
Table
1
(OPPTS
Guideline
860.1000).
2
Contribution
=
[tolerance
/
%
DM
(if
cattle)]
X
%
diet).
3
All
beef
and
dairy
cattle
in
the
U.
S.
should
have
in
their
diet
15%
cottonseed
meal,
peanut
meal,
soybean
meal,
canola
meal,
or
flax
seed
meal.
Hexazinone
is
not
registered
for
use
on
any
of
these
commodities.
Therefore,
to
account
for
these
commodities
in
the
diet
of
beef
and
dairy
cattle,
the
percentage
has
been
reduced
by
15%
to
85%.
Dairy
cattle
feeding
study
28
A
brief
summary
of
the
reviewed
dairy
cattle
feeding
study
(MRID
43703501)
is
presented
below.
Three
groups
of
dairy
cows
(3
animals/
dose
group)
were
dosed
with
hexazinone
at
29,
87,
and
290
ppm
in
the
diet
for
28
consecutive
days;
three
additional
cows
served
as
control
animals.
The
registrant
indicated
that
these
dose
levels
represent
feeding
level
of
1.0x,
3.0x,
and
10.0x
based
on
a
diet
of
grass
forage.
These
dose
levels
are
equivalent
to
6.25x,
18.75x,
and
62.5x,
respectively,
the
maximum
theoretical
dietary
burden
for
beef
and
dairy
cattle
when
grass
or
grass
hay
is
not
included.
An
additional
treatment
group,
fed
at
17.4
ppm
(3.88x),
was
added
later,
and
one
animal
was
held
over
from
the
control
group
for
this
phase
of
the
study.
These
dose
levels
are
equivalent
to
64x,
190x,
and
640x
the
MTDB
for
hogs.
Hexazinone
was
placed
into
gelatin
capsules
and
administered
by
balling
gun,
twice
daily
after
each
milking.
Milk
was
collected
twice
daily.
The
cattle
were
sacrificed
13
21
hours
after
administration
of
the
final
dose,
and
samples
of
liver,
kidney,
muscle,
and
fat
were
collected.
The
collected
milk
and
tissue
samples
were
analyzed
for
residues
of
hexazinone
and
its
metabolites
using
two
analytical
methods.
One
method
was
used
for
milk,
muscle,
and
fat,
and
another
method
for
liver
and
kidney.
Although
cumbersome
and
complicated,
the
method
was
deemed
adequate
for
data
collection.
Based
on
the
data
collection
method
used
in
this
study,
the
registrant
is
now
proposing
an
LC/
MS
method
(designated
as
du
Pont
AMR
3783
96)
as
an
enforcement
method
for
milk
and
animal
tissues.
Refer
to
"GLN
860.1340:
Residue
Analytical
Methods
Animal
Commodities"
for
a
discussion
of
this
method
and
a
list
of
specific
hexazinone
residues
that
the
method
can
determine.
Assuming
Method
AMR
3783
96
passes
a
successful
tolerance
method
validation,
the
tolerance
expression
for
milk
and
tissues
will
be
changed.
The
maximum
total
hexazinone
residues
in
milk
were
0.78
ppm
at
the
6.25x
feeding
level
(29
ppm
in
the
diet)
and
11.09
ppm
at
the
62.5x
level.
On
day
14,
after
total
residues
had
reached
plateaus,
milk
was
separated
into
skim
milk
and
cream.
Total
residues
in
skim
milk
were
comparable
to
those
in
whole
milk;
total
residues
in
cream
were
approximately
half
those
in
skim
milk.
In
tissues,
the
maximum
total
hexazinone
residues
at
the
62.5x
feeding
level
were
3.85
ppm
in
liver,
2.19
ppm
in
kidney,
0.32
ppm
in
muscle,
and
nondetectable
(
#
0.10
ppm)
in
fat.
The
maximum
total
residues
at
the
6.25x
feeding
level
were
0.24
ppm
in
liver,
0.47
ppm
in
kidney,
and
nondetectable
(
#
0.15
ppm)
in
muscle.
Because
total
residues
were
nondetectable
in
all
fat
samples
from
the
18.75x
and
62.5x
levels,
fat
samples
were
not
analyzed
at
lower
feeding
levels.
A
tolerances
of
0.5
ppm
is
presently
established
for
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone)
in
milk.
Based
on
the
MTDB
for
beef
and
dairy
cattle
without
grass
or
grass
hay
as
a
potential
feed
item,
it
is
possible
to
re
assess
the
animal
commodity
tolerances.
The
HED
MARC
has
concluded
that
the
hexazinone
tolerance
expression
for
ruminants
should
include
29
hexazinone
plus
metabolites
B,
C,
C
2,
and
F
for
milk.
Residue
levels
of
hexazinone
and
metabolites
in
whole
milk
from
the
feeding
study
corrected
for
exaggeration
levels
ranged
from
0.110
ppm
to
0.164
ppm.
Based
on
the
enforcement
method,
the
sum
of
the
LOQ's
for
hexazinone
and
metabolites
B,
C,
C
2,
and
F
is
0.20
ppm;
therefore,
it
is
appropriate
that
the
tolerance
for
milk
be
reduced
from
0.5
to
0.20
ppm.
Tolerances
of
0.1
ppm
are
presently
established
for
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone)
in
fat,
meat,
and
meat
byproducts
of
cattle,
goats,
hogs,
horses,
and
sheep.
The
Committee
concluded
that
the
hexazinone
tolerance
expression
for
ruminant
tissue
should
include
hexazinone
plus
metabolites
B
and
F.
Residue
levels
of
hexazinone
and
metabolites
in
kidney
from
the
feeding
study
corrected
for
exaggeration
levels
ranged
from
0.046
ppm
to
0.090
ppm.
Based
on
the
enforcement
method,
the
sum
of
the
LOQ's
for
hexazinone
and
metabolites
B
and
F
is
0.10
ppm
therefore
it
is
appropriate
that
the
tolerance
for
meat
byproducts
of
cattle,
goats,
horses,
and
sheep
be
reassessed
at
0.10
ppm.
Residue
levels
of
hexazinone
and
metabolites
from
the
feeding
study
corrected
for
exaggeration
levels
ranged
from
0.003
ppm
to
0.007
ppm
therefore
tolerances
for
hog
meat
are
not
required.
Residue
levels
of
hexazinone
and
metabolites
in
muscle
from
the
feeding
study
corrected
for
exaggeration
levels
ranged
from
0.003
ppm
to
0.039
ppm.
Based
on
the
enforcement
method,
the
sum
of
the
LOQ's
for
hexazinone
and
metabolites
B
and
F
is
0.10
ppm;
therefore,
it
is
appropriate
that
the
tolerance
for
meat
byproducts
of
cattle,
goats,
horses,
and
sheep
be
reassessed
at
0.10
ppm.
Residue
levels
of
hexazinone
and
metabolites
in
muscle
from
the
feeding
study
corrected
for
exaggeration
levels
ranged
from
0.0004
ppm
to
0.002
ppm
therefore
tolerances
for
hog
meat
are
not
required.
Tolerances
of
0.1
ppm
are
presently
established
for
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone)
in
fat.
Residue
levels
of
hexazinone
and
metabolites
in
fat
from
the
feeding
study
were
nondetectable
(<
0.1
ppm)
at
the
62.5x
exaggerated
rate.
The
Agency
has
determined
that
tolerances
for
hexazinone
residues
in
fat
of
cattle,
goats,
hogs,
horses,
and
sheep
are
not
required
(Category
3,
40
CFR
§180.6a).
Tolerances
for
fat
of
cattle,
goats,
hogs,
horses,
and
sheep
are
not
required
and
should
be
revoked.
GLN
860.1400:
Water,
Fish,
and
Irrigated
Crops
Hexazinone
is
presently
not
registered
for
direct
use
on
water
and
aquatic
food
and
feed
crops;
therefore,
no
residue
chemistry
data
are
required
under
these
guideline
topics.
GLN
860.1460:
Food
Handling
30
Hexazinone
is
presently
not
registered
for
use
in
food
handling
establishments;
therefore,
no
residue
chemistry
data
are
required
under
this
guideline
topic.
GLN
860.1850:
Confined
Accumulation
in
Rotational
Crops
The
data
requirements
for
confined
rotational
crops
are
satisfied.
The
basic
registrant
has
submitted
acceptable
studies
(MRIDs
41008401,
42824001,
43892401)
which
indicate
that
[
14
C]
hexazinone
residues
accumulate
at
0.01
ppm
in/
on
tested
rotational
crop
commodities
at
certain
plantback
intervals.
Based
on
these
data,
the
registrant
was
required
to
conduct
a
limited
field
rotational
crop
study
in
order
to
assess
the
adequacy
of
existing
rotational
crop
restrictions
on
the
registrant's
end
use
product
labels
and
to
determine
whether
rotational
crop
tolerances
are
needed.
The
major
residue
components
that
were
identified
from
the
confined
rotational
crop
study
were
either
the
glucose
conjugate
of
G3170
or
hexazinone
or
both.
The
remaining
ten
identified
metabolites
all
contain
the
triazinone
ring
structure,
and
four
of
these
compounds
(metabolites
A,
B,
C,
and
F)
have
been
determined
to
be
residues
of
concern
in/
on
primary
crops.
GLN
860.1900:
Field
Accumulation
in
Rotational
Crops
The
data
requirements
for
field
accumulation
in
rotational
crops
are
only
partially
satisfied.
This
conclusion
is
based
on
a
recent
review
of
a
limited
field
crop
rotation
study
(MRID
45084101)
wherein
the
75%
DF
formulation
of
hexazinone
was
applied
as
a
single
postemergence
broadcast
application
to
mowed
alfalfa
at
test
sites
in
MN
and
CA
at
1.5
lb
ai/
A
(1x
the
maximum
seasonal
rate
for
alfalfa).
Approximately
one
year
following
application,
the
remaining
alfalfa
crop
residue
was
plowed
up
and
returned
to
the
soil,
and
head
lettuce,
field
corn,
and
wheat
were
planted
(350
days
after
treatment,
DAT,
for
the
MN
test
site
and
358
DAT
for
the
CA
test
site).
Residues
were
below
the
respective
method
LOQs
for
hexazinone
and
metabolites
A,
B,
C,
D,
E,
F,
G,
H,
G3170,
G3170
NG,
A
1,
and
C
1
in/
on
head
lettuce,
wheat
forage
and
grain,
and
field
corn
forage
and
grain.
In
wheat
straw,
residues
of
metabolite
B
were
<0.02
0.021
ppm;
residues
of
hexazinone
and
the
remaining
metabolites
were
below
the
LOQ.
In
field
corn
stover,
residues
of
hexazinone
were
0.02
0.081
ppm,
residues
of
metabolite
B
were
0.038
0.053
ppm,
and
residues
of
the
remaining
metabolites
were
below
the
LOQ.
These
data
indicate
that
extended
field
rotational
crop
studies
and
rotational
crop
tolerances
will
not
be
required
for
residues
of
hexazinone
residues
of
concern
in/
on
leafy
vegetables
provided
that
labels
are
amended
to
specify
a
rotational
crop
restriction
of
at
least
12
months.
A
previous
review
of
a
confined
rotational
crop
study
concluded
31
that
rotational
crop
tolerances
were
not
needed
for
root
crops
provided
that
a
12
month
plantback
interval
was
established;
an
examination
of
the
basic
registrant's
labels
shows
that
the
12
month
plantback
interval
for
root
crops
has
been
established.
Because
the
data
from
the
limited
field
trials
indicate
that
quantifiable
residues
occur
in
field
corn
stover
and
wheat
straw,
extended
field
rotational
crop
trials
for
corn
stover,
sorghum
stover,
and
wheat
straw
to
support
a
12
month
rotational
interval
and
a
tolerance
for
inadvertent
hexazinone
residues
are
required.
The
data
for
the
application
rate
used
in
this
study
are
sufficient
to
support
rotation
from
alfalfa
and
pasture
and
rangeland
grass
only.
The
registrant
has
stated
previously
that
they
intend
to
modify
product
labels
to
restrict
rotation
from
sugarcane
to
sugarcane
only
(HED
memorandum,
10/
31/
96,
J.
Abbotts).
32
Table
B.
Residue
Chemistry
Science
Assessments
for
Reregistration
of
Hexazinone.
GLN:
Data
Requirements
Tolerances
[40
CFR]
(ppm)
Must
Additional
Data
Be
Submitted?
References
1
860.1200:
Directions
for
Use
N/
A
=
Not
Applicable
Yes
2
See
Table
A
860.1300:
Plant
Metabolism
N/
A
No
00078047,
00104846,
00126127
860.1300:
Animal
Metabolism
N/
A
No
00104843,
41524801,
42187901
3
,
42219301
4
,
42248901
5
,
42690601
6
,
43488901
7
860.1340:
Residue
Analytical
Methods
Plant
commodities
N/
A
No
00038868,
00101574,
00126127,
41964101,
41964102,
42987201
8
,
430025401
9
Animal
commodities
N/
A
Reserved
10
00038868,
43074201
11
,
44259101
12
,
44259102
12
860.1360:
Multiresidue
Methods
N/
A
No
41572101,
41572102,
41572103,
41572104,
41572105,
41572106
860.1380:
Storage
Stability
Data
Plant
commodities
N/
A
No
42276001
13
,
42322701
14
,
42418001
15
,
42423001
16
,
42492101
17
,
42535601
18
,
42867501
19
,
43524301
20
,
43936501
21
,
44133501
22
Animal
commodities
N/
A
No
43703501
23
860.1500:
Crop
Field
Trials
Berries
Group
Blueberries
0.2
[§
180.396(
a)]
No
24
00101574,
41964101,
41964102
Grass
Forage,
Fodder,
Hay
Group
GLN:
Data
Requirements
Tolerances
[40
CFR]
(ppm)
Must
Additional
Data
Be
Submitted?
References
1
33
Grasses
(pastures
and
rangeland),
forage
and
hay
10,
grasses,
pasture
and
rangeland
[§
180.396(
a)]
Yes
25,
26
00138226,
41898301
27
,
42419101
15
,
42867501
19
Table
B
(continued).
GLN:
Data
Requirements
Tolerances
[40
CFR]
(ppm)
Must
Additional
Data
Be
Submitted?
References
1
34
Non
grass
Animal
Feeds
(forage,
fodder,
straw,
and
hay)
Group
Alfalfa,
forage,
hay,
and
seed
2.0,
forage
8.0,
hay
[§
180.396(
a)]
No
28
,
29
00118050,
43074401
30
,
43074402
30
Miscellaneous
Commodities
Pineapple
0.
5,
whole
fruit
[§
180.396(
a)]
No
00126127,
42535601
18
Sugarcane
0.
2
[§
180.396(
c)]
No
00028733,
00114039,
42322701
14
860.1520:
Processed
Food/
Feed
Pineapple
None
No
42492101
17
,
43401901
31
Sugarcane
5.
0,
molasses
[§
180.396(
c)]
No
42276001
13
,
42417901
32
,
PP#
8F2119/
FAP#
4H5683
33
860.1480:
Meat,
Milk,
Poultry,
Eggs
Milk,
Fat,
Meat,
and
Meat
Byproducts
of
Cattle,
Goats,
Hogs,
Horses,
and
Sheep
0.1,
milk,
fat,
meat,
and
meat
byproducts
[§
180.396(
a)]
No
34
00028866,
00140161,
43703501
23
Eggs
and
the
Fat,
Meat,
and
Meat
Byproducts
of
Poultry
None
No
35
00104845
860.1400:
Water,
Fish,
and
Irrigated
Crops
NA
No
860.1460:
Food
Handling
NA
No
860.1850:
Confined
Rotational
Crops
NA
No
41008401
36
,
42824001
37
,
43892401
38
860.1900:
Field
Rotational
Crops
None
Yes
39
45084101
40
Table
B
(continued).
35
1.
Bolded
references
were
reviewed
in
the
Reregistration
Update
of
9/
5/
91.
Unbolded
references
were
reviewed
in
the
Residue
Chemistry
Science
Chapter
of
the
Final
Registration
Standard
and
Tolerance
Reassessment
(FRSTR)
dated
5/
25/
88.
All
other
references
were
reviewed
as
noted.
2.
Label
amendments
are
required
for
alfalfa
and
blueberries,
and
details
of
the
required
label
amendments
are
presented
in
the
respective
endnote
for
GLN
860.1500
(Crop
Field
Trials)
of
this
table.
Label
amendments
are
also
required
to
establish
a
12
month
plantback
interval
for
leafy
vegetables.
3.
DP
Barcode
D174764,
CBRS
No.
9418,
5/
22/
92,
J.
Abbotts.
4.
DP
Barcode
D175243,
CBRS
No.
9510,
7/
14/
92,
J.
Abbotts.
5.
DP
Barcode
D176715,
CBRS
No.
9697,
9/
15/
92,
J.
Abbotts.
6.
DP
Barcode
D189285,
CBRS
No.
11656,
6/
25/
93,
J.
Abbotts.
7.
DP
Barcode
D210574,
CBRS
No.
14889,
1/
19/
95,
J.
Abbotts.
8.
DP
Barcode
D196446,
CBRS
No.
12815,
1/
6/
94,
J.
Abbotts.
9.
DP
Barcode
D197342,
CBRS
No.
12932,
1/
6/
94,
J.
Abbotts.
10.
The
registrant
has
proposed
an
LC/
MS
method
(designated
as
du
Pont
AMR
3783
96)
as
an
enforcement
method
for
animal
commodities.
Method
AMR
3783
96
has
been
subjected
to
a
successful
ILV
and
a
radiovalidation
study.
Method
AMR
3783
96
will
be
forwarded
to
the
Analytical
Chemistry
Branch
(ACL;
Beltsville,
MD)
for
a
tolerance
method
validation
by
Agency
chemists.
If
the
results
of
method
validation
are
successful,
then
Method
AMR
3783
96
will
be
proposed
for
inclusion
in
PAM
Volume
II,
and
no
additional
enforcement
methodology
for
animal
commodities
will
be
required
for
reregistration.
11.
DP
Barcode
D198348,
CBRS
No.
13076,
5/
25/
94,
S.
Hummel.
12.
DP
Barcode
D282683,
05/
15/
02,
J.
S.
Punzi.
13.
DP
Barcode
D177572,
CBRS
No.
9808,
6/
18/
92,
S.
Funk.
14.
DP
Barcode
D178771,
CBRS
No.
9985,
9/
22/
92,
J.
Abbotts.
15.
DP
Barcode
D181318,
CBTS
No.
10354,
1/
28/
93,
R.
Lascola.
16.
DP
Barcode
D181480,
CBRS
No.
10365,
11/
9/
92,
J.
Abbotts.
17.
DP
Barcode
D183296,
CBRS
No.
10702,
2/
23/
93,
J.
Abbotts.
18.
DP
Barcode
D184852,
CBRS
No.
10924,
2/
25/
93,
J.
Abbotts.
19.
DP
Barcode
D195426,
CBRS
No.
12617,
10/
25/
93,
J.
Abbotts.
20.
DP
Barcode
D211642,
CBRS
No.
15101,
3/
14/
95,
J.
Abbotts.
21.
DP
Barcode
D282685,
05/
15/
02,
J.
S.
Punzi.
Table
B
(continued).
36
22.
DP
Barcode
D282682,
05/
15/
02,
J.
Punzi.
23.
DP
Barcode
D217257,
CBRS
No.
15881,
9/
25/
95,
J.
Abbotts.
24.
No
additional
data
are
required
for
blueberries.
However,
label
revisions
remain
a
requirement.
The
product
labels
for
ME980002
and
ME980003,
which
are
limited
for
use
on
lowbush
blueberries,
should
be
amended
to
specify
a
PHI
of
450
days.
The
product
label
for
NC830012
should
also
be
amended
to
specify
PHIs
of
90
and
450
days
for
application
to
highbush
and
lowbush
blueberries,
respectively.
25.
Uses
on
grass
should
be
cancelled
and
tolerances
revoked.
The
following
grass
forage
would
be
required
for
grass:
"Data
depicting
magnitude
of
the
residues
of
hexazinone
and
metabolites
A,
B,
C,
D,
and
E
in/
on
grass
forage
harvested
0
day
following
a
single
broadcast
application
of
representative
formulations
at
1.125
lb
ai/
A.
It
is
the
Agency
policy
to
require
0
day
crop
field
residue
data
for
grass
forage
unless
it
is
not
feasible
(e.
g.,
preplant/
preemergence
pesticide
uses).
The
formulations
to
be
tested
may
be
applied
in
side
by
side
plots.
The
location
and
number
of
trials
should
be
in
compliance
with
the
current
OPPTS
GLN
for
adequate
geographic
representation
of
data.
26.
Uses
on
grass
should
be
cancelled
and
tolerances
revoked.
Additional
grass
hay
data
would
be
required.
The
registrant
has
submitted
a
petition
(PP#
1F3967)
for
the
establishment
of
a
tolerance
for
residues
of
hexazinone
and
its
metabolites
in/
on
grass
hay.
The
petition
is
currently
in
reject
status
because
additional
grass
hay
data,
from
field
trials
with
adequate
geographical
representation,
remain
outstanding.
27.
DP
Barcodes
D165324,
D165303,
and
D165277,
CBRS
Nos.
8147,
8148,
8149,
8134,
8152,
and
8153,
11/
14/
91,
J.
Smith.
28.
No
additional
data
are
required
for
alfalfa
forage
and
hay.
However,
the
product
label
for
the
2
lb/
gal
EC
(EPA
Reg.
No.
352
392)
formulation
must
be
amended
to
establish
a
30
day
PHI
(or
pregrazing
interval)
for
the
feeding
of
forage
and
the
cutting
of
hay.
29.
No
additional
data
are
required
for
alfalfa
seed.
However,
the
registrant
is
required
to
propose
a
tolerance
for
hexazinone
residues
of
concern
in/
on
alfalfa
seed;
the
available
data
suggest
that
a
tolerance
level
of
2.0
ppm
is
appropriate.
30.
DP
Barcode
D198336,
CBRS
No.
13075,
6/
22/
94,
S.
Hummel.
31.
DP
Barcode
D208605,
CBRS
No.
14591,
1/
20/
95,
C.
Eiden
and
DP
Barcode
D215057,
11/
28/
95,
C.
Eiden.
32.
DP
Barcode
D181308,
CBRS
No.
10333,
10/
26/
92,
B.
Cropp
Kohlligian.
33.
DP
Barcode
D196510,
CB
No.
12796,
9/
1/
94,
S.
Hummel.
34.
An
acceptable
dairy
cattle
feeding
study
is
available.
HED
is
able,
at
this
time,
to
reassess
the
established
hexazinone
tolerances
for
milk
and
the
fat,
meat,
and
meat
byproducts
of
livestock
using
maximum
theoretical
dietary
burdens
of
hexazinone
to
livestock,
calculated
without
grass
or
grass
hay.
Since
additional
residue
data
are
required
for
grass
forage
and
hay,
for
which
significant
residues
are
expected
in/
on
the
RACs
and
are
considered
major
dietary
components
of
ruminants,
HED
recommends
that
the
uses
be
canceled
and
tolerances
revoked.
35.
HED
has
determined
that
tolerances
for
hexazinone
residues
in
eggs
and
poultry
tissues
are
not
required
(Category
3,
40
CFR
§180.6)
based
on
the
results
of
the
reviewed
poultry
metabolism
study.
36.
DP
Barcode
D188349,
CBRS
No.
11458,
5/
14/
93,
L.
Cheng.
Table
B
(continued).
37
37.
DP
Barcode
D192877,
CBRS
No.
12222,
3/
3/
94,
F.
Fort.
38.
DP
Barcode
D222455,
CBRS
No.
16791,
7/
1/
96,
L.
Cheng.
39.
Because
the
data
from
the
limited
field
trials
indicate
that
quantifiable
residues
occur
in
field
corn
stover
and
wheat
straw,
extended
field
rotational
crop
trials
for
corn
stover,
sorghum
stover,
and
wheat
straw
to
support
a
12
month
rotational
interval
and
a
tolerance
for
inadvertent
hexazinone
residues
are
required.
40.
DP
Barcode
D282684,
05/
15/
02,
J.
S.
Punzi.
38
TOLERANCE
REASSESSMENT
SUMMARY
Tolerances
for
residues
of
hexazinone
in/
on
plant,
livestock,
and
processed
commodities
are
currently
expressed
in
terms
of
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone).
Permanent
tolerances
are
established
for
several
raw
agricultural
commodities
and
livestock
commodities
under
40
CFR
§180.396(
a).
Tolerances
with
regional
registrations
which
exclude
use
of
hexazinone
on
sugarcane
in
Florida
are
established
under
40
CFR
§180.396(
c).
The
qualitative
nature
of
the
residue
in
plants
and
livestock
is
adequately
understood.
The
HED
MARC
concluded
that
the
hexazinone
tolerance
expression
for
plants
and
rotational
crops
should
include
hexazinone
and
metabolites
A,
B,
C,
D,
and
E.
The
qualitative
nature
of
the
residue
in
livestock
is
adequately
understood
based
on
acceptable
ruminant
and
poultry
metabolism
studies.
The
HED
MARC
concluded
that
the
hexazinone
tolerance
expression
for
ruminants
should
include
hexazinone
plus
metabolites
B,
C,
C
2,
and
F
for
milk.
The
Committee
concluded
that
the
hexazinone
tolerance
expression
for
ruminant
tissue
should
include
hexazinone
plus
metabolites
B
and
F.
The
Committee
concluded
that
residues
of
hexazinone
and
metabolites
B,
C,
C1
C
2,
and
F
should
be
taken
into
account
when
risk
assessments
are
done.
HED
has
determined
that
tolerances
for
hexazinone
residues
in
eggs
and
poultry
tissues,
hog
meat
and
meat
by
products,
and
fat
of
livestock
are
not
required
(Category
3,
40
CFR
§180.6)
based
on
the
results
of
the
respective
metabolism
and
feeding
studies.
An
adequate
enforcement
method
is
available
for
plant
commodities.
Method
I
of
PAM,
Volume
II
is
a
nitrogen
selective
GLC
method
capable
of
determining
residues
of
hexazinone
and
metabolites
A,
B,
C,
D,
and
E.
The
combined
limit
of
quantitation
(LOQ)
for
hexazinone
residues
by
Method
I
is
0.55
ppm.
An
enforcement
method,
Method
AMR
3783
96,
has
been
proposed
for
milk
and
livestock
tissues.
Method
AMR
3783
96
has
been
subjected
to
a
successful
ILV
and
a
radiovalidation
study.
It
will
be
forwarded
to
the
Analytical
Chemistry
Branch
for
a
tolerance
method
validation
by
Agency
chemists.
HED
is
recommending
that
the
hexazinone
tolerances
listed
under
40
CFR
§180.396
(a)
and
(c)
be
reorganized,
as
listed
below,
to
indicate
the
specific
residues
of
concern
that
can
be
quantitated
by
the
existing
plant
enforcement
method
and
the
proposed
livestock
enforcement
method.
This
proposal
to
reorganize
hexazinone
tolerances
is
contingent
upon
successful
validation
of
Method
AMR
3783
96.
Note
that
for
simplicity
the
tolerence
expression
is
shown
as
"Hexazinone
and
its
metabolites
A,
B,
C,
D,
and
E
(calculated
as
hexazinone)"
however
the
metabolites
must
be
identified
by
the
appropriate
chemical
name.
Table
4.
39
40
CFR
Reserved
for
Tolerance
Expression
§180.396
(a)
(1)
Permanent
tolerances
for
plant
and
processed
commodities
Hexazinone
and
its
metabolites
A,
B,
C,
D,
and
E
(calculated
as
hexazinone)
§180.396
(a)
(2)
Milk
Hexazinone
and
its
metabolite
B,
metabolite
C
and
its
isomer
(C
2),
and
metabolite
F
(calculated
as
hexazinone)
§180.396
(a)
(3)
Ruminant
tissues
Hexazinone
and
its
metabolite
B
and
metabolite
F
(calculated
as
hexazinone)
§180.396
(c)
Tolerances
for
plant
and
processed
commodities
with
regional
registration
Hexazinone
and
its
metabolites
A,
B,
C,
D,
and
E
(calculated
as
hexazinone)
NOTE:
See
Figure
1
for
full
chemical
names
of
regulated
hexazinone
metabolites.
A
summary
of
hexazinone
tolerance
reassessments
is
presented
in
Table
C.
Discussions
of
residue
data
used
for
tolerance
reassessment
are
presented
in
the
"Summary
of
Science
Findings"
section
for
GLNs
860.1500
(Crop
Field
Trials)
and
860.1480
(Meat,
Milk,
Poultry,
and
Eggs).
Certain
commodity
definitions
need
to
be
corrected.
Tolerances
Listed
Under
40
CFR
§180.396
(a):
Sufficient
data
are
available
to
ascertain
the
adequacy
of
tolerances
listed
in
40
CFR
§180.96
(a)
for
alfalfa
forage,
alfalfa
hay,
blueberries,
and
pineapple.
Tolerances
for
pasture
and
rangeland
grasses
should
be
revoked
and
uses
cancelled.
An
acceptable
ruminant
feeding
study
is
available;
HED
is
able
to
reassess
the
established
hexazinone
tolerances
for
milk
and
the
fat,
meat,
and
meat
byproducts
of
livestock
using
a
maximum
theoretical
dietary
burden
of
hexazinone
to
livestock
assuming
revocation
of
tolerances
for
grasses
and
hay.
The
established
tolerances
for
blueberries
and
pineapple
should
be
increased
to
0.60
ppm
to
reflect
the
combined
LOQs
of
the
enforcement
method.
The
available
field
trial
data
indicate
that
residues
of
hexazinone
and
its
regulated
metabolites,
as
measured
by
the
data
collection
method,
were
nondetectable
in/
on
these
RACs
following
treatment
at
1.0x.
Tolerances
Needed
Under
40
CFR
§180.396
(a):
The
registrant
is
required
to
propose
a
tolerance
for
hexazinone
residues
of
concern
in/
on
alfalfa
seed;
the
available
data
suggest
that
a
tolerance
level
of
2.0
ppm
is
appropriate.
Tolerances
Listed
Under
40
CFR
§180.396
(c):
40
Adequate
data
are
available
for
sugarcane
and
sugarcane
molasses.
The
tolerance
for
sugarcane
molasses
should
be
reduced
from
5.0
ppm
to
4.0
ppm
based
on
re
calculation
of
expected
residues.
41
(continued;
endnotes
follow)
Table
C.
Tolerance
Reassessment
Summary
for
Hexazinone.
Commodity
Current
Tolerance
(ppm)
a
Range
of
residues
(ppm)
b
Tolerance
Reassessment
(ppm)
Comment/
Correct
Commodity
Definition
Tolerances
listed
under
40
CFR
§180.396(
a):
Alfalfa
green
forage
2
<1.87
2.0
Alfalfa,
forage
Alfalfa
hay
8
<3.33
4.
0
Alfalfa,
hay
Blueberries
0.2
<0.3
ppm
(nondetectable;
<0.05
ppm
for
each
compound)
0.60
Tolerance
should
be
increased
based
on
the
combined
LOQ
(0.55
ppm)
of
the
enforcement
method.
Blueberry
Cattle,
fat
0.
1
Revoke
c
Cattle,
mbyp
0.1
0.
10
Cattle,
meat
0.1
0.
10
Goat,
fat
0.
1
Revoke
c
Goat,
mbyp
0.1
0.
10
Goats,
meat
0.1
0.
10
Grasses,
pasture
10
Revoke
d
Grass,
forage
Grass,
hay
Grasses,
rangeland
10
Revoke
d
Hog,
fat
0.1
Revoke
c
Hog,
mbyp
0.1
Revoke
c
Hog,
meat
0.1
Revoke
c
Horses,
fat
0.
1
Revoke
c
Horses,
mbyp
0.1
0.
10
Horses,
meat
0.1
0.
10
Milk
0.5
0.
20
Pineapple
0.
5
<0.35
(or
<0.05
ppm
for
each
compound)
0.60
Tolerance
should
be
increased
based
on
the
combined
LOQ
(0.55
ppm)
of
the
enforcement
method.
Sheep,
fat
0.
1
Revoke
c
Sheep,
mbyp
0.1
0.
10
Sheep,
meat
0.1
0.
10
Tolerances
needed
under
40
CFR
§180.396(
a):
Alfalfa,
seed
<1.30<
1.46
2.
0
Table
C
(continued).
Commodity
Current
Tolerance
(ppm)
a
Range
of
residues
(ppm)
b
Tolerance
Reassessment
(ppm)
Comment/
Correct
Commodity
Definition
42
Tolerances
listed
under
40
CFR
§180.396(
c):
Sugarcane
0.
2
<0.05
ppm
(nondetectable)
each
for
hexazinone
and
its
metabolites
0.60
Tolerance
should
be
increased
based
on
the
combined
LOQ
(0.55
ppm)
of
the
enforcement
method.
Sugarcane
molasses
5
(1.915
x
4x)
÷
2x
=
3.83
4.0
a
Expressed
in
terms
of
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone).
b
Refer
to
section
on
Magnitude
of
Residues
in
Crop
Plant
for
detailed
discussion
of
residues
in
crops.
c
Tolerances
for
fat
are
not
required
(Category
3,
40
CFR
§180.6).
d
HED
is
recommending
revocation
of
these
tolerances
and
cancellation
of
uses,
since
grasses
are
a
major
feed
item
and
required
data
are
not
available
for
reassessment.
CODEX
HARMONIZATION
No
maximum
residue
limits
(MRLs)
for
hexazinone
and
its
metabolites
have
been
established
or
proposed
by
Codex
for
any
agricultural
commodity.
Therefore,
no
compatibility
questions
exist
with
respect
to
U.
S.
tolerances..
43
AGENCY
MEMORANDA
CITATIONS
Agency
Memoranda
Citations
Relevant
to
Hexazinone
Reregistration.
Date
DP
Barcode
CB
No.
From
To
MRID
Nos.
Subject
7/
18/
91
D162863
7835
R.
Lascola
J.
Miller/
D.
Wilson
None
PP#
1F3967.
Hexazinone
(Velpar
L)
in/
on
Pasture
and
Rangeland
Hay.
11/
14/
91
D165277,
D165303,
D165324
8134,
8147,
8148,
8149,
8152,
8153
J.
Smith
J.
Miller
41898301
Hexazinone.
Amendment
of
label
reflecting
a
new
pregrazing
interval
for
forestry
use,
new
replanting
instructions
following
alfalfa,
reduced
use
on
sugarcane,
and
overall
clarifications.
3/
11/
92
D174869
9463
D.
McNeilly
A.
Ertman
None
Hexazinone
reregistration;
question
concerning
pineapple
forage
feeding
restriction
from
DuPont
Agricultural
Products.
5/
22/
92
D174764
9418
J.
Abbotts
L.
Rossi
42187901
Hexazinone.
Du
Pont
Company
Response
to
the
Reregistration
Standard:
Animal
Metabolism
Data
for
Goat.
6/
18/
92
D177572
9808
S.
Funk
A.
Ertman
42276001
Reregistration
of
Hexazinone
(Velpar).
171
4(
l):
Sugarcane
Processing
Study.
171
4(
K):
Sugarcane
Field
Trial
Time
Extension
Request.
6/
24/
92
D172408
9127
R.
Lascola
E.
Wilson/
J.
Miller
None
PP#
1F3967.
Hexazinone
(Velpar
L)
in/
on
Pasture
and
Rangeland
Hay.
Amended
Response
to
Registration
Standard
Data
Gap.
7/
14/
92
D175243
9510
J.
Abbotts
L.
Rossi
42219301
Hexazinone.
Du
Pont
Company
Response
to
the
Reregistration
Standard:
Storage
Stability
Data
for
Animal
Metabolism
in
Poultry.
8/
21/
92
D178781
9961
J.
Abbotts
A.
Ertman
None
Hexazinone.
Du
Pont
Company
Response
to
the
Reregistration
Update
to
the
Residue
Chemistry
Chapter.
Agency
Memo
Citations
for
Hexazinone
(continued).
Date
DP
Barcode
CB
No.
From
To
MRID
Nos.
Subject
44
8/
25/
92
D174070
9366
M.
Bradley
J.
Miller
None
Hexazinone.
Label
Amendment
to
Add
Pregrazing
Intervals
for
Forestry
and
Non
Crop
Land
Use.
9/
15/
92
D176715
9697
J.
Abbotts
L.
Rossi
42248901
Hexazinone.
Du
Pont
Company
Response
to
the
Reregistration
Standard:
Storage
Stability
Data
for
Animal
Metabolism
in
Goat.
9/
22/
92
D178771
9985
J.
Abbotts
L.
Rossi
42322701
Hexazinone.
Du
Pont
Company
Response
to
the
Reregistration
Standard:
Residue
Data
for
Sugarcane.
10/
26/
92
D181308
10333
B.
Cropp
Kohlligian
L.
Rossi
42417901
Hexazinone:
Supplemental
Data
Submitted
to
Address
Sugarcane
Processing
Study
Deficiencies.
11/
9/
92
D181480
10365
J.
Abbotts
L.
Rossi
42423001
Hexazinone.
Du
Pont
Company
Response
to
the
Reregistration
Standard:
Storage
Stability
Data
for
Blueberry.
1/
28/
93
D181318
10354
R.
Lascola
E.
Wilson/
J.
Miller
42418001
and
42419101
PP
1F3967.
Hexazinone
(Velpar
L)
in/
on
Pasture
and
Rangeland
Hay.
2/
4/
93
None
None
R.
Perfetti
L.
Rossi
and
E.
Saito
None
Animal
Feeding
Studies:
Requirement
Status
Modification.
2/
23/
93
D183296
10702
J.
Abbotts
L.
Rossi
42492101
Hexazinone.
Du
Pont
Company
Response
to
the
Reregistration
Standard:
Processing
Data
for
Pineapple.
2/
25/
93
D184852
10924
J.
Abbotts
L.
Rossi
42535601
Hexazinone.
Du
Pont
Company
Response
to
the
Reregistration
Standard:
Residue
Data
for
Pineapple.
5/
14/
93
D188349
11458
L.
Cheng
A.
Ertman/
W.
Waldrop
41008401
Hexazinone.
Rotational
Crop
Data
Requirement.
6/
25/
93
D189285
11656
J.
Abbotts
A.
Ertman
42690601
Hexazinone,
Reregistration.
Supplemental
Data
on
Poultry
Metabolism.
Agency
Memo
Citations
for
Hexazinone
(continued).
Date
DP
Barcode
CB
No.
From
To
MRID
Nos.
Subject
45
7/
22/
93
None
None
R.
Perfetti
L.
Rossi
and
A.
Rathman
None
Animal
Feeding
Studies.
Requirement
Status
Modification:
Reconsideration.
9/
9/
93
None
None
M.
Metzger
L.
Rossi
None
Animal
Feeding
Studies
(171
4(
j));
Requirement
Status
Modification.
10/
5/
93
D194489
12425
J.
Abbotts
A.
Ertman
None
Hexazinone,
Reregistration.
Animal
Feeding
Study
Protocol.
10/
5/
93
D194395
12427
J.
Abbotts
A.
Ertman
None
Hexazinone,
Reregistration.
Pineapple
Residue
Data.
10/
8/
93
None
None
J.
Abbotts
L.
Rossi
and
F.
Chow/
C.
Frick
None
Hexazinone.
Reregistration
Eligibility
Document
Chapters
for
Product
Chemistry
and
Residue
Chemistry,
Current
Status.
10/
8/
93
None
None
J.
Abbotts
Hexazinone
Reregistration
File
None
Hexazinone.
Anticipated
Residues
for
Reregistration
Eligibility
Document.
10/
25/
93
D195426
12617
J.
Abbotts
A.
Ertman
42867501
Hexazinone,
Reregistration.
Storage
Stability
Data
in
Grass.
1/
6/
94
D196446
12815
J.
Abbotts
A.
Ertman
42987201
Hexazinone,
Reregistration.
Analytical
Method
for
Sugarcane
Commodities.
1/
6/
94
D197342
12932
J.
Abbotts
A.
Ertman
43025401
Hexazinone,
Reregistration.
Independent
Laboratory
Validation
of
an
Analytical
Method
for
Sugar
Commodities.
3/
3/
94
D192877
12222
F.
Fort
L.
Rossi/
W.
Waldrop
42824001
Hexazinone.
Supplemental
Information
Pertaining
to
Rotational
Crop
Requirements.
List
A
Case
No.
0266.
Chemical
I.
D.
No.
107201.
3/
16/
94
D199887
13301
S.
Hummel
A.
Ertman
None
Hexazinone
(107201),
Reregistration
Case
No.
0266.
Storage
Intervals
and
Conditions
in
Grass
Time
Extension
Request
for
Livestock
Feeding
Study.
Agency
Memo
Citations
for
Hexazinone
(continued).
Date
DP
Barcode
CB
No.
From
To
MRID
Nos.
Subject
46
4/
20/
94
D201203
13492
F.
Suhre
A.
Ertman
None
Hexazinone
(ID
107201).
Magnitude
of
the
Residue,
Cattle
Feeding
Study
[171
4(
j)];
Protocol
Amendment.
4/
29/
94
D201738
13527
G.
Kramer
E.
Wilson/
J.
Miller
None
PP#
1F3967.
Hexazinone
(Velpar
L)
in/
on
Pasture
and
Rangeland
Hay.
Amendment
of
3/
28/
94.
5/
16/
94
None
None
S.
Hummel
Metabolism
Committee
None
Hexazinone
(107201),
Reregistration
Case
No.
0266.
Issues
to
be
Presented
to
the
Metabolism
Committee.
5/
25/
94
D198348
13076
S.
Hummel
A.
Ertman
43074201
Hexazinone
(107201),
Reregistration
Case
No.
266.
Livestock
Metabolism
Confirmatory
Analyses
Hexazinone
Tolerance
Expression.
5/
25/
94
D203472
None
S.
Hummel
HED
Metabolism
Committee
None
Hexazinone
(107201)
Plant
and
Animal
Metabolism:
Results
of
HED
Metabolism
Committee
Meeting
Held
May
19,
1994.
6/
1/
94
D202919
13649
F.
Suhre
W.
Waldrop
None
Hexazinone
(107201).
Pineapple
Processing
Study
171
4(
l).
6/
22/
94
D198336
13075
S.
Hummel
A.
Ertman
43074401
and
43074402
Hexazinone
(107201)
Residue
Data
on
Alfalfa.
9/
1/
94
D196510
12796
S.
Hummel
E.
Wilson/
J.
Miller/
A.
Ertman
None
PP#
8F2119/
FAP#
4H5683
Hexazinone
(107201)
Residue
Data
on
Sugarcane
Reregistration
Case
No.
0266.
9/
8/
94
D207225
14319
S.
Hummel
A.
Ertman
None
Hexazinone
(107201)
Reregistration
Case
No.
0266.
Updated
Table
A
for
Residue
Chemistry
RED
Chapter.
9/
22/
94
D207493
14363
S.
Hummel
E.
Wilson/
J.
Miller/
A.
Ertman
None
PP#
8F2119/
FAP#
4H5683
Hexazinone
(107201)
on
Sugarcane
Reregistration
Case
No.
0266.
Clarification
of
CB
12796,
DP
Barcode
D196510.
Agency
Memo
Citations
for
Hexazinone
(continued).
Date
DP
Barcode
CB
No.
From
To
MRID
Nos.
Subject
47
10/
12/
94
D207995
14455
S.
Hummel
E.
Wilson/
J.
Miller/
A.
Ertman
None
PP#
8F2119/
FAP#
4H5683
Hexazinone
(107201)
on
Sugarcane
Amendment
of
9/
21/
94
EPA
Reg.
No.
352
378
DuPont
Velpar
Herbicide
Reregistration
Case
No.
0266
Amended
Registration,
Deletion
of
Use
in
FL.
11/
30/
94
D209648
14740
S.
Hummel
E.
Wilson/
A.
Ertman
None
PP#
8F2119/
FAP#
4H5683
Hexazinone
(107201)
on
Sugarcane
Amendment
of
11/
2/
94,
Draft
FR
Notice
EPA
Reg.
No.
352
378
DuPont
Velpar
Herbicide
Reregistration
Case
No.
0266
Justification
for
Disallowing
Use
in
FL.
1/
19/
95
D210574
14899
J.
Abbotts
A.
Ertman
43488901
Hexazinone
(107201),
Reregistration
Case
0266.
Ruminant
Metabolism,
Supplemental
Data.
1/
20/
95
D208605
14591
C.
Eiden
W.
Waldrop
43401901
Hexazinone.
Pineapple
Processing
Study.
3/
14/
95
D211642
15101
J.
Abbotts
A.
Ertman
43524301
Hexazinone
(107201),
Reregistration
Case
0266.
Storage
Stability
of
Metabolite
C
in
Grass,
Interim
Report.
9/
25/
95
D217257
15881
J.
Abbotts
A.
Ertman
43703501
Hexazinone
(107201),
Reregistration
Case
0266.
Cattle
Feeding
Study.
11/
28/
95
D215057
15974
C.
Eiden
W.
Waldrop/
A.
Ertman
None
Hexazinone.
Pineapple
Processing
Study
Follow
Up:
Response
from
Registrant.
4/
15/
96
None
None
J.
Abbotts
A.
Ertman
None
Hexazinone
(107201),
Reregistration
Case
0266.
Meeting
with
Registrant
DuPont,
4/
9/
96,
on
Progress
Toward
Analytical
Method,
Animal
Commodities.
7/
1/
96
D222455
16791
L.
Cheng
P.
Deschamp
43892401
Hexazinone.
Case
0266.
Confined
Rotational
Crop
Studies
(GLN
165
1).
9/
27/
96
D228808
17552
J.
Abbotts
M.
Metzger
None
Hexazinone
(107201),
Reregistration
Case
0266.
Registrant
DuPont
Agricultural
Products.
Guideline
860.1900.
Field
Rotational
Crops,
Limited.
Agency
Memo
Citations
for
Hexazinone
(continued).
Date
DP
Barcode
CB
No.
From
To
MRID
Nos.
Subject
48
10/
31/
96
None
None
J.
Abbotts
P.
Deschamp
None
Hexazinone
(107201),
Reregistration
Case
0266.
Meeting
with
Registrant
DuPont,
10/
30/
96,
on
Requirements
for
Limited
Field
Rotational
Trials.
02/
05/
02
D279897
None
S.
Kinard
C.
Olinger
None
Hexazinone.
The
Outcome
of
the
HED
Metabolism
Assessment
Review
Committee.
05/
15/
02
D282685
None
J.
Punzi
D.
Helder
43936501
Hexazinone
(107201),
Reregistration
Case
0266.
Storage
Stability
Study
for
Hexazinone
and
Metabolites
A,
B,
C,
D,
and
E
in
Pasture
and
Range
Grasses.
05/
15/
02
D282682
None
J.
Punzi
D.
Helder
44133501
Hexazinone
(107201),
Reregistration
Case
0266.
Storage
Stability
Study
for
Hexazinone
and
Metabolites
A,
B,
C,
D,
and
E
in
Alfalfa
Forage,
Hay,
and
Seed.
05/
15/
02
D282683
None
J.
Punzi
D.
Helder
44259101
Hexazinone
(107201),
Reregistration
Case
0266.
Enforcement
Method
For
the
Determination
of
Hexazinone
and
its
Metabolites
in
Animal
Tissue
and
Milk
Using
ESI
LC/
MS
05/
15/
02
D282683
None
J.
Punzi
D.
Helder
44259102
Hexazinone
(107201),
Reregistration
Case
0266.
Independent
Laboratory
Validation
of
Proposed
Enforcement
Method
For
the
Determination
of
Hexazinone
and
its
Metabolites
in
Animal
Tissue
and
Milk
Using
ESI
LC/
MS
05/
15/
02
D282684
None
J.
Punzi
D.
Helder
45084101
Hexazinone
(107201),
Reregistration
Case
0266.
Field
Accumulation
in
Rotational
Crops
49
STUDY
CITATIONS
00028733
E.
I.
du
Pont
de
Nemours
&
Company
(1976)
Determination
of
Hexazinone
Metabolite
C.
Undated
method.
(Unpublished
study
received
Jan
21,
1980
under
352
378;
CDL:
099225
A)
00028866
Holt,
R.
F.;
Baude,
F.
J.;
More,
D.
W.
(1979)
Hexazinone
Livestock
Feeding
Studies:
Milk
and
Meat.
(Unpublished
study
received
Mar
14,
1980
under
352
378;
submitted
by
E.
I.
du
Pont
de
Nemours
&
Co.,
Wilmington,
Del.;
CDL:
099298
F)
00038868
Holt,
R.
F.
(1980)
Determination
of
Hexazinone
and
Metabolite
Residues
Using
Nitrogen
Selective
Gas
Chromatography.
Undated
method.
(Unpublished
study
received
Jul
1,
1980
under
352
378;
submitted
by
E.
I.
du
Pont
de
Nemours
&
Co.,
Wilmington,
Del.;
CDL:
099514
E)
00038869
Rapisarda,
C.
(1978)
Metabolism
of
14C
Labeled
Hexazinone
in
the
Goat.
(Unpublished
study
received
Jul
1,
1980
under
352
378;
submitted
by
E.
I.
du
Pont
de
Nemours
&
Co.,
Wilmington,
Del.;
CDL:
099514
F)
00078047
Rhodes,
R.
C.
(1975)
Letter
sent
to
324
File
dated
Aug
12,
1975:
Uptake
and
metabolism
studies
with
14
C
DPX
3674
on
sugarcane
in
the
greenhouse.
(Unpublished
study
received
Mar
22,
1976
under
352
EX
91;
submitted
by
E.
I.
du
Pont
de
Nemours
&
Co.,
Wilmington,
Del.;
CDL:
095980
E)
00101574
Interregional
Research
Project
No.
4
(1982)
Residue
Studies
of
Hexazinone
on
Blueberries
and
Methomyl
on
Sugarcane.
(Compilation;
unpublished
study
received
May
17,
1982
under
2E2687;
CDL:
070861
A)
00104843
Study
ADP
record
deleted.
Study
is
a
duplicate
of
MRID
38869
00104845
E.
I.
du
Pont
de
Nemours
&
Co.,
Inc.
(1979)
Results
of
Tests
on
the
Amount
of
Residue
Remaining
on
Treated
Crop:
Hexazinone
plus
Metabolites.
(Compilation;
unpublished
study
received
May
24,
1979
under
9G2214;
CDL:
098309
C)
00104846
Rapisarda,
C.
Metabolism
of
14C
labeled
Hexazinone
in
Alfalfa:
Doc.
No.
HME
12
79.
(Unpublished
study
received
May
24,
1979
under
9G2214;
submitted
by
E.
I.
du
Pont
de
Nemours
&
Co.,
Inc.,
Wilmington,
DE;
CDL:
098309
D)
00114039
E.
I.
du
Pont
de
Nemours
&
Co.,
Inc.
(1978)
Investigations
Made
with
Respect
to
Residue
Chemistry:
[Velpar].
(Compilation;
unpublished
50
study
received
Aug
29,
1978
under
352
378;
CDL:
097321
E)
00118050
E.
I.
du
Pont
de
Nemours
&
Co.,
Inc.
(1982)
Data
Supporting
Amendment
of
Velpar
Weed
Killer
Use
on
Alfalfa
and
Adding
Velpar
L
Weed
Killer
Use
on
Alfalfa.
(Unpublished
study
received
Nov
15,
1982
under
352
378;
CDL:
248831
A)
00126127
E.
I.
du
Pont
de
Nemours
&
Co.,
Inc.
(1983)
Results
of
Tests
on
the
Amount
of
Residue
Remaining
on
Treated
Crop:
Hexazinone.
(Compilation;
unpublished
study
received
Feb
28,
1983
under
352
378;
CDL:
071438
A)
00138226
E.
I.
du
Pont
de
Nemours
&
Co.,
Inc.
(1984)
Residue
Chemistry
Data
Supporting
the
Use
of
Velpar
L
Weed
Killer
for
Control
of
Undesirable
Woody
Plants
in
Rangeland.
(Compilation;
unpublished
study
received
Apr
4,
1984
under
352
392;
CDL:
252954
A)
00140161
Magnitude
of
the
Residue
in
Animals
41008401
Rapisarda,
C.
(1980)
Rotational
Crop
Studies
with
14C
LabeledHexazinone
Laboratory
Project
AMR
26
80.
Unpublished
study
prepared
by
E.
I.
du
Pont
de
Nemours
&
Co.
25
p.
41524801
Hawkins,
W.;
Elsom,
L.;
Gray,
S.,
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al.
(1990)
The
Metabolism
of
Carbon
14
Hexazinone
in
Laying
Hens:
Lab
Project
Number:
203/
90454:
AMR
1517
89.
Unpublished
study
prepared
by
Huntingdon
Research
Centre,
Ltd.
80
p.
41572101
Fomenko,
J.
(1990)
Testing
of
DPX
A3674
through
FDA
Multi
Residue
Protocols
A
E:
Lab
Project
Number:
AMR
1489
89:
DP001
01.
Unpublished
study
prepared
by
Spectralytix.
67
p.
41572102
Fomenko,
J.
(1990)
Testing
of
IN
T3937
through
FDA
Multi
Residue
Protocols
A
E:
Lab
Project
Number:
AMR
1490
89:
DP001
02.
Unpublished
study
prepared
by
Sprectalytix
Inc.
57
p.
41572103
Fomenko,
J.
(1990)
Testing
of
IN
A3928
through
FDA
Multi
Residue
Protocols
A
E:
Lab
Project
Number:
AMR
1491
89:
DP001
03.
Unpublished
study
prepared
by
Spectralytix,
Inc.
67
p.
41572104
Fomenko,
J.
(1990)
Testing
of
IN
T3935
through
FDA
Multi
Residue
Protocols
A
E:
Lab
Project
Number:
AMR
1492
89:
DP001
04.
Unpublished
study
prepared
by
Spectralytix
Inc.
57
p.
51
41572105
Fomenko,
J.
(1990)
Testing
of
IN
B2838
through
FDA
Multi
Residue
Protocols
A
E:
Lab
Project
Number:
AMR
1493
89:
DP001
05.
Unpublished
study
prepared
by
Spectralytix
Inc.
67
p.
41572106
Fomenko,
J.
(1990)
Testing
of
IN
B3936
through
FDA
Multi
Residue
Protocols
A
E:
Lab
Project
Number:
AMR
1494
89:
DP001
06.
Unpublished
study
prepared
by
Spectralytix
Inc.
67
p.
41898301
Bollin,
E.
(1991)
Magnitude
of
Residues
of
Velpar
Herbicide
in
Pasture
and
Range
Grasses:
Lab
Project
Number:
AMR
1429
89.
Unpublished
study
prepared
by
E.
I.
du
Pont
de
Nemours
and
Co.
241
p.
41964101
Bollin,
E.;
Hay,
R.
(1991)
Magnitude
of
Residues
of
Velpar
and
Velpar
L
Herbicide
in
Lowbush
Blueberries:
Lab
Project
Number:
AMR
1431
89.
Unpublished
study
prepared
by
E.
I.
du
Pont
de
Nemours
and
Co.
46
p.
41964102
Bollin,
E.;
Hay,
R.
(1991)
Magnitude
of
Residues
of
Velpar
and
Velpar
L
Herbicide
in
Highbush
Blueberries:
Lab
Project
Number:
AMR
1434
89.
Unpublished
study
prepared
by
E.
I.
du
Pont
de
Nemours
and
Co.
46
p.
42187901
Hawkins,
D.;
Elsom,
L.;
Dighton,
M.;
et
al.
(1992)
The
Metabolism
of
Carbon
14
Hexazinone
in
the
Goat:
Lab
Project
Number:
245/
91718:
AMR
1906
90.
Unpublished
study
prepared
by
Huntingdon
Research
Centre
Ltd.
105
p.
42219301
Hawkins,
D.;
Elsom,
L.;
Dighton,
M.;
(1992)
The
Metabolism
of
Carbon
14
Hexazinone
in
Laying
Hens:
The
Freezer
Storage
Stability
of
Tissues,
Eggs
and
Excreta
from
Laying
Hens
Dosed
with
Carbon
14
Hexazinone:
Supplement
to:
Lab
Project
Number:
HRC/
203/
90454;
AMR
1517
89.
Unpublished
study
prepared
by
Huntingdon
Research
Centre
Ltd.
33
p.
42248901
Hawkins,
D.;
Elsom,
L.;
Dighton,
M.
(1992)
The
Metabolism
of
Carbon
14
Hexazinone
in
the
Goat,
Supplement
1:
The
Freezer
Storage
Stability
of
Carbon
14
Residues
in
Tissues
and
Milk
from
a
Lactating
Goat
Dosed
with
Carbon
14
Hexazinone:
Lab
Project
Number:
HRC/
DPT
245/
91718:
AMR
1906
90.
Unpublished
study
prepared
by
Huntingdon
Research
Centre.
36
p.
42276001
Powley,
C.;
Tomic,
D.
(1992)
Magnitude
of
the
Residue
of
Velpar
Herbicide
in
Sugarcane
and
its
Processed
Fractions:
Lab
Project
Number:
AMR
1473
89:
35
5300:
14
5308.
Unpublished
study
prepared
by
Dupont
and
Hawaiian
Sugar
Planters
Association.
151
p.
52
42322701
Powley,
C.;
Tomic,
D.
(1992)
Magnitude
of
Residues
of
Velpar
Herbicide
in
Sugarcane:
Lab
Project
Number:
AMR
1472
89:
14
5308.
Unpublished
study
prepared
by
E.
I.
DuPont
de
Nemours
and
Co.
and
Hawaiian
Sugar
Planters
Assoc.
180
p.
42417901
Mulcahey,
L.
(1992)
Magnitude
of
the
Residues
of
Velpar
Herbicide
in
Sugarcane
and
its
Processed
Fractions
(Supplemental):
Lab
Project
Number:
AMR
1473
89
(SUPP
1):
35
5300:
14
5308.
Unpublished
study
prepared
by
E.
I.
DuPont
de
Nemours
and
Co.
in
coop
with
the
Hawaiian
Sugar
Planters'
Assoc.
40
p.
42418001
Klemens,
A.;
Tomic,
D.
(1992)
Freezer
Storage
Stability
of
Hexazinone
and
Metabolites
in
Pasture
and
Range
Grasses.
Lab
Project
Number:
AMR
1582
90:
A022.005.
Unpublished
study
prepared
by
E.
I.
DuPont
de
Nemours
and
Co.
in
coop
with
Huntingdon
Analytical
Services.
54
p.
42419101
Mulcahey,
L.
(1992)
Magnitude
of
Residues
of
Velpar
Herbicide
in
Pasture
and
Range
Grasses:
A
Supplement:
Lab
Project
Number:
AMR
1429
89:
1022.004:
91012.
Unpublished
study
prepared
by
E.
I.
du
Pont
de
Nemours
and
Co.
89
p.
42423001
Klemens,
A.;
Devine,
P.
(1992)
Freezer
Storage
Stability
of
Velpar
Herbicide
and
Metabolites
on
Blueberries:
Lab
Project
Number:
AMR
1911
90.
Unpublished
study
prepared
by
E.
I.
DuPont
de
Nemours
and
Co.
47
p.
42492101
Powley,
C.;
Tomic,
D.
(1992)
Magnitude
of
Residues
of
Velpar
Herbicide
in
the
Processed
Fractions
of
Pineapples:
Lab
Project
Number:
AMR
1471
89:
MP
90
03.01:
36
5309.
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study
prepared
by
E.
I.
du
Pont
de
Nemours
&
Co.
114
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42535601
Powley,
C.;
Tomic,
D.
(1992)
Magnitude
of
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of
Velpar
Herbicide
in
Pineapples:
Lab
Project
Number:
AMR
1570
89:
36
5309.
Unpublished
study
prepared
by
E.
I.
du
Pont
de
Nemours
and
Co.;
Hawaiian
Sugar
Planters'
Association.
81
p.
42690601
Hawkins,
D.
R.;
Elsom,
L.
F.;
Gray,
S.
P.,
et
al.
(1990)
The
Metabolism
of
14C
Hexazinone
in
Laying
Hens,
Supplement
2.
Du
Pont
AMR
1517
89,
Supplement
2.
Unpublished
study
prepared
by
E.
I.
du
Pont
de
Nemours
&
Co.,
Inc.
42824001
Rapisarda,
C.
(1993)
Rotational
Crop
Studies
with
(carbon
14)
Labeled
Hexazinone:
Supplement
No.
1:
Lab
Project
Number:
AMR
26
80.
Unpublished
study
prepared
by
E.
I.
du
Pont
de
Nemours
and
Co.
11
p.
53
42867501
Klemens,
A.;
Devine,
P.
(1993)
Freezer
Storage
Stability
of
Hexazinone
and
Metabolites
in
Pasture
and
Range
Grasses:
Supplement
No.
1:
Lab
Project
Number:
AMR
1582
90:
A022.005.
Unpublished
study
prepared
by
E.
I.
du
Pont
de
Nemours
and
Co.
and
Huntingdon
Analytical
Services.
72
p.
42987201
Powley,
C.;
Zhou,
M.;
DeBernard,
P.
(1993)
Method
for
the
Determination
of
Hexazinone
in
Sugarcane
and
Processed
Fractions:
Lab
Project
Number:
AMR
2654
93.
Unpublished
study
prepared
by
DuPont
Agricultural
Products.
30
p.
43025401
Bruns,
G.
(1993)
Independent
Laboratory
Validation
of
the
Analytical
Enforcement
Method
for
the
Determination
of
Hexazinone
in
Sugarcane,
Molasses,
and
Bagasse
by
Gas
Chromatography:
Lab
Project
Number:
DUP69/
REP:
AMR/
2804/
93.
Unpublished
study
prepared
by
Enviro
Test
Labs.
34
p.
43074201
Hawkins,
D.;
Elsom,
L.;
Dighton,
M.;
et
al.
(1993)
A
Comparison
of
(carbon
14)
Hexazinone
Metabolites
in
Hen
Tissues
and
Eggs
and
Goat
Tissues
and
Milk
Synthesised
Metabolite
Standards:
Lab
Project
Number:
294/
932331:
DPT/
294/
932331:
HRC/
DPT/
294/
932331.
Unpublished
study
prepared
by
Huntingdon
Research
Centre
Ltd.
110
p.
43074401
Djanegara,
T.;
Devine,
P.
(1993)
Magnitude
of
Residues
of
Hexazinone
in
Alfalfa
Forage,
Hay,
and
Seed
Grown
in
the
Western
United
States
Following
Application
of
Velpar
Herbicide:
Lab
Project
Number:
AMR
1924
91:
92013.
Unpublished
study
prepared
by
E.
I.
du
Pont
de
Nemours
&
Co.
and
Spectralytix,
Inc.
330
p.
43074402
Djanegara,
T.;
Devine,
P.
(1993)
Magnitude
of
Residues
of
Hexazinone
in
Alfalfa
Forage
and
Hay
Grown
in
the
Eastern
United
States
Following
Application
of
Velpar
Herbicide:
Lab
Project
Number:
AMR
2010
91:
92025.
Unpublished
study
prepared
by
E.
I.
du
Pont
de
Nemours
&
Co.
and
Spectralytix,
Inc.
316
p.
43401901
Powley,
C.;
Devine,
P.
(1994)
Magnitude
of
Residues
of
Velpar
Herbicide
in
the
Processed
Fractions
of
Pineapples:
Supplement
No.
1:
Lab
Project
Number:
MP/
90/
03/
01:
5309:
AMR/
1471/
89.
Unpublished
study
prepared
by
E.
I.
du
Pont
de
Nemours
and
Co.;
Maui
Pineapple
Co.,
Ltd.;
and
Hawaiian
Sugar
Planters'
Association.
74
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43488901
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D.;
Elsom,
L.;
Dighton,
M.
et
al.
(1994)
A
Comparison
of
(carbon
14)
Hexazinone
Metabolites
in
Hen
Tissues
and
Eggs
and
Goat
Tissues
and
Milk
With
Synthesised
Metabolite
Standards:
Supplement
1:
54
Examples
of
Calculations
and
Chromatographic
Raw
Data:
Lab
Project
Number:
DPT
294/
932331:
AMR
2633
93.
Unpublished
study
prepared
by
Huntingdon
Research
Centre,
Ltd.
94
p.
43524301
Mulcahey,
L.;
Orescan,
D.
(1995)
Freezer
Storage
Stability
of
Hexazinone
and
Metabolites
in
Pasture
and
Range
Grasses:
Supplement
No.
2:
Lab
Project
Number:
AMR
1582
90:
HAS
A022.005:
SPX
92020.
Unpublished
study
prepared
by
DuPont
Agricultural
Products;
Huntingdon
Analytical
Services;
and
Spectralytix.
76
p.
43703501
Mulcahey,
L.;
George,
S.;
Brisbin,
J.
et
al.
(1995)
Magnitude
of
Residues
of
Hexazinone
in
Edible
Tissues
and
Milk
of
Lactating
Dairy
Cows:
Lab
Project
Number:
.
43892401
Djanegara,
T.;
Reardon
Green,
L.
(1996)
Confined
Accumulation
Study
of
(4
Carbonyl(
carbon
14))
Hexazinone
(DPX
A3674)
in
Rotational
Crops:
Lab
Project
Number:
AMR
2800
93.
Unpublished
study
prepared
by
DuPont
Agricultural
Products.
115
p.
Relatesto
letter
L0000071.
43936501
Mulcahey,
L.
(1996)
Freezer
Storage
Stability
of
Hexazinone
and
Metabolites
in
Pasture
and
Range
Grasses:
Supplement
No.
3
(Final):
Lab
Project
Number:
AMR
1582
90:
HAS
A022.005:
SPX
92020.
Unpublished
study
prepared
by
DuPont
Agricultural
Products;
Huntingdon
Analytical
Services
and
Environmental
Analytical
Services.
63
p.
44133501
Bollin,
E.
(1996)
Magnitude
of
the
Residue
of
Hexazinone
in
Alfalfa
Forage,
Hay,
and
Seed
Grown
in
the
Western
United
States
Following
Application
of
Velpar
Herbicide:
Supplement
No.
1
to
MRID
43074401:
Lab
Project
Number:
AMR
1924
91:
92013.
Unpublished
study
prepared
by
DuPont
Agricultural
Products
and
Environmental
Analytical
Services,
Inc.
40
p.
44259101
Brill,
F.;
Bramble,
F.;
Norwood,
G.;
et
al.
(1997)
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Analytical
Method
for
the
Determination
of
Hexazinone
and
Metabolites
of
Interest
in
Animal
Tissues
and
Milk
Using
ESI
LC/
MS:
Lab
Project
Number:
AMR
3783
96.
Unpublished
study
prepared
by
E.
I.
du
Pont
de
Nemours
and
Co.
100
p.
44259102
Xu,
B.
(1997)
Independent
Laboratory
Validation
of
a
Proposed
Enforcement
Analytical
Method
for
the
Determination
of
Hexazinone
and
Metabolites
of
Interest
in
Animal
Tissue
and
Milk
Using
ESI
LC/
MS:
Lab
Project
Number:
AMR
4366
97:
008
07.
Unpublished
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prepared
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Inc.
117
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Brill,
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Magnitude
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Rotational
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Following
Application
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Velpar
Herbicide
at
Maximum
Label
Rates
to
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Number:
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4336
97.
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I.
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| epa | 2024-06-07T20:31:42.914317 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0019/content.txt"
} |
EPA-HQ-OPP-2002-0188-0020 | Supporting & Related Material | "2002-09-16T04:00:00" | null | [Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
1
of
13
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
05/
14/
2002
SUBJECT:
Hexazinone
Acute
and
Chronic
Dietary
Exposure
Assessments
for
the
TRED.
PC
Code:
107201
DP
Barcode:
D279898
REVIEWER:
John
S.
Punzi,
Ph.
D.,
Chemist
Reregistration
Branch
II
Health
Effects
Division
(7509C)
THROUGH:
Richard
Griffin,
DESAC
Reviewer
Branch/
Health
Effects
Division
(7509C)
Alan
Nielsen,
Branch
Senior
Scientist
Branch/
Health
Effects
Division
(7509C)
TO:
Dirk
Helder,
Chemical
Review
Manager
Reregistration
Branch
II
Special
Review
and
Reregistration
Division
(7509C)
and
Carol
Christensen,
Risk
Assessor
Reregistration
Branch
II
Health
Effects
Division
(7509C)
Executive
Summary
The
purpose
of
this
memorandum
is
to
report
the
results
of
a
Tier
1
dietary
exposure
analysis
for
hexazinone.
In
this
analysis
the
acute
and
chronic
dietary
exposure
and
risk
estimates
resulting
from
food
intake
were
determined
for
the
U.
S.
population
and
various
population
subgroups.
[Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
2
of
13
Acute
and
chronic
dietary
exposure
assessments
were
performed
in
order
to
determine
the
exposure
and
risk
estimates
which
result
from
the
use
of
hexazinone
on
the
crops
included
in
the
reregistration
eligibility
decision.
Hexazinone
residues
of
concern
for
plants
are
parent
plus
metabolites
A,
B,
C,
D,
E
(see
D279897,
S.
Kinard
02/
05/
2002)
for
structures
and
metabolite
discussion).
The
tolerance
values
for
hexazinone
in/
on
blueberry,
pineapple,
and
sugarcane
are
based
on
the
analytical
method's
limit
of
quantitation
(LOQ)
and
all
non
detectable
residues
were
found
in
residue
studies
(see
D279899,
J.
Punzi,
05/
15/
2002).
This
analysis
used
a
single
residue
estimate
based
on
the
reassessed
tolerance
for
blueberry,
pineapple,
and
sugarcane.
Default
processing
factors
and
100%
crop
treated
were
used
for
residue
input
into
DEEM.
Hexazinone
residues
of
concern
in
ruminant
milk
are
hexazinone
plus
metabolites
B,
C,
C
2,
and
F.
Hexazinone
residues
of
concern
in
ruminant
tissue
are
hexazinone
plus
metabolites
B
and
F.
For
purposes
of
risk
assessment
however,
the
residues
of
concern
in
livestock
milk
and
tissue
are
hexazinone
plus
metabolites
B,
C,
C
1,
C
2,
and
F.
The
livestock
feeding
study
indicates
significant
residues
in
milk
at
all
feeding
levels
and
quantifiable
residues
in
kidney.
When
the
residue
levels
are
corrected
for
exaggerated
rates
the
values
are
less
than
the
sum
of
the
LOQ's
for
the
residues
of
concern.
Based
on
the
analytical
method's
LOQ
the
reside
estimate
for
meats
and
milk
are
0.24
ppm.
Default
processing
factors
and
100%
crop
treated
were
used
for
residue
input
into
DEEM.
The
chronic
dietary
risk
estimates
are
provided
for
the
U.
S.
population
(total)
and
various
population
subgroups.
This
assessment
concludes
that
the
exposure
is
below
HED's
level
of
concern
for
all
population
subgroups
examined.
Exposures,
as
a
percentage
of
the
RfD,
ranged
from
approximately
3%
for
females
aged
13
through
50
years
to
15%
for
children
aged
1
through
6
years.
The
acute
dietary
risk
estimates
are
provided
for
the
population
subgroup
consisting
of
females
aged
13
through
50
years
only.
This
assessment
concludes
that
the
exposure
is
below
HED's
level
of
concern
for
this
subgroup.
Exposures
as
a
percentage
of
the
RfD
are
calculated
to
be
less
than
1%
at
the
95
th
percentile.
I.
Introduction
Dietary
risk
assessment
incorporates
both
exposure
and
toxicity
of
a
given
pesticide.
For
acute
and
chronic
assessments,
the
risk
is
expressed
as
a
percentage
of
a
maximum
acceptable
dose.
This
dose
is
the
highest
daily
dose
which
HED
has
deemed
will
pose
no
unreasonable
adverse
health
effects
and
is
called
the
population
adjusted
dose
(PAD).
The
PAD
is
equivalent
to
the
Reference
Dose
(RfD)
divided
by
the
FQPA
Safety
Factor.
Dietary
risk
is
expressed
as
a
percentage
of
the
PAD.
HED's
level
of
concern
is
exceeded
when
the
dietary
risk
exceeds
100%
of
the
PAD.
References
which
discuss
the
acute
and
chronic
risk
assessments
in
more
detail
are
available
on
the
EPA/
pesticides
web
site:
"Available
Information
on
Assessing
Exposure
from
Pesticides,
A
User's
Guide",
6/
21/
2000,
web
link:
[Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
3
of
13
http://
www.
epa.
gov/
fedrgstr/
EPA
PEST/
2000/
July/
Day
12/
6061.
pdf
;
or
see
SOP
99.6
(8/
20/
99).
II.
Residue
Information
Hexazinone
tolerances
are
established
under
40
CFR
§180.396
(a)
and
(b).
The
tolerance
for
plant
and
animal
commodities,
is
currently
expressed
in
terms
of
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone).
Tolerances
are
currently
established
for;
alfalfa;
alfalfa
hay;
blueberries;
cattle,
goat,
hog,
and
horse
fat,
meat,
and
meat
by
products;
range
grasses,
pasture
grasses,
milk,
pineapple
and
sugarcane.
Current
tolerances
range
from
0.1
ppm
in/
on
meats
and
milk
to
10
ppm
on
grasses.
Reassessed
tolerances
range
from
0.1
ppm
to
4
ppm.
Tolerances
are
not
currently
needed
for
livestock
fat,
hog
meat,
and
hog
meat
by
products.
HED
is
recommending
that
in
order
to
reassess
the
established
hexazinone
tolerances
for
milk
and
the
fat,
meat,
and
meat
byproducts
of
livestock
and
to
compute
a
maximum
theoretical
dietary
burden
(MTDB)
of
hexazinone
to
livestock,
uses
on
pasture
and
rangland
grasses
must
be
revoked.
A
MTDB
could
not
be
calculated
including
grass
and
grass
hay
since
additional
residue
data
are
required
for
use
patterns
in
which
significant
residues
are
expected
in/
on
the
RACs.
HED
recognizes
that
the
estimated
100,000
acres
of
pasture
and
rangeland
treated
with
hexazinone
is
relatively
low.
Since
grass
and
grass
hay
are
considered
major
dietary
components
of
ruminants
(up
to
60%
of
the
diet
per
current
OPPTS
GLN)
a
MTDB
for
livestock
could
not
be
developed
when
grasses
are
included
in
the
registered
uses.
HED
has
determined
that
a
MTDB
could
be
constructed
from
other
potential
feed
items
for
livestock
and
subsequently
tolerances
for
meats
and
milk
can
be
reassessed.
Hexazinone
residues
of
concern
for
plants
are
parent
plus
metabolites
A,
B,
C,
D,
E
(see
D279897,
S.
Kinard
02/
05/
2002,
for
structures
and
metabolite
discussion).
The
tolerance
values
for
hexazinone
in/
on
blueberry,
pineapple,
and
sugarcane
are
based
on
the
analytical
method's
limit
of
quantitation
(LOQ)
and
all
non
detectable
residues
were
found
in
residue
studies
(see
D279899,
J.
Punzi,
05/
05/
2002).
This
analysis
used
a
single
residue
estimate
based
on
the
reassessed
tolerance
for
blueberry,
pineapple,
and
sugarcane.
Default
processing
factors
and
100%
crop
treated
were
used
for
residue
input
into
DEEM.
Hexazinone
residues
of
concern
in
ruminant
milk
are
hexazinone
plus
metabolites
B,
C,
C
2,
and
F.
Hexazinone
residues
of
concern
in
ruminant
tissue
are
hexazinone
plus
metabolites
B
and
F.
For
purposes
of
risk
assessment
however,
the
residues
of
concern
in
livestock
milk
and
tissue
are
hexazinone
plus
metabolites
B,
C,
C
1,
C
2,
and
F.
The
livestock
feeding
study
indicates
significant
residues
in
milk
at
all
feeding
levels
and
quantifiable
residues
in
kidney.
When
the
residue
levels
are
corrected
for
exaggerated
rates
the
values
are
less
than
the
sum
of
the
LOQ's
for
the
residues
of
concern.
Based
on
the
analytical
method's
LOQ
the
reside
estimate
for
meats
and
milk
are
0.24
ppm.
Default
processing
factors
and
100%
crop
treated
were
used
for
residue
input
into
DEEM.
[Hexazinone]
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Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
4
of
13
Residue
Data
used
for
Acute
and
Chronic
Assessments:
This
TIER
1
analysis
used
a
single
residue
estimate
based
on
the
reassessed
tolerance
for
blueberry,
pineapple,
and
sugarcane.
Default
processing
factors
and
100%
crop
treated
were
used
for
residue
input
into
DEEM.
For
purposes
of
risk
assessment
however,
the
residues
of
concern
in
livestock
milk
and
tissue
are
hexazinone
plus
metabolites
B,
C,
C
1,
C
2,
and
F.
The
same
data
are
being
used
in
both
acute
and
chronic
analysis.
III.
DEEM™
Program
and
Consumption
Information
Hexazinone
acute
and
chronic
dietary
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(DEEM™)
software,
Version
[7.76],
which
incorporates
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intake
by
Individuals
(CSFII),
1989
1992.
The
1989
92
data
are
based
on
the
reported
consumption
of
more
than
10,000
individuals
over
three
consecutive
days,
and
therefore
represent
more
than
30,000
unique
"person
days"
of
data.
Foods
"as
consumed"
(e.
g.,
apple
pie)
are
linked
to
raw
agricultural
commodities
and
their
food
forms
(e.
g.,
apples
cooked/
canned
or
wheat
flour)
by
recipe
translation
files
internal
to
the
DEEM
software.
Consumption
data
are
averaged
for
the
entire
U.
S.
population
and
within
population
subgroups
for
chronic
exposure
assessment,
but
are
retained
as
individual
consumption
events
for
acute
exposure
assessment.
For
chronic
exposure
and
risk
assessment,
an
estimate
of
the
residue
level
in
each
food
or
foodform
(e.
g.,
orange
or
orange
juice)
on
the
commodity
residue
list
is
multiplied
by
the
average
daily
consumption
estimate
for
that
food/
food
form.
The
resulting
residue
consumption
estimate
for
each
food/
food
form
is
summed
with
the
residue
consumption
estimates
for
all
other
food/
food
forms
on
the
commodity
residue
list
to
arrive
at
the
total
average
estimated
exposure.
Exposure
is
expressed
in
mg/
kg
body
weight/
day
and
as
a
percent
of
the
cPAD.
This
procedure
is
performed
for
each
population
subgroup.
For
acute
exposure
assessments,
individual
one
day
food
consumption
data
are
used
on
an
individual
by
individual
basis.
The
reported
consumption
amounts
of
each
food
item
can
be
multiplied
by
a
residue
point
estimate
and
summed
to
obtain
a
total
daily
pesticide
exposure
for
a
deterministic
(Tier
1
or
Tier
2)
exposure
assessment,
or
"matched"
in
multiple
random
pairings
with
residue
values
and
then
summed
in
a
probabilistic
(Tier
3/
4)
assessment.
The
resulting
distribution
of
exposures
is
expressed
as
a
percentage
of
the
aPAD
on
both
a
user
(i.
e.,
those
who
reported
eating
relevant
commodities/
food
forms)
and
a
per
capita
(i.
e.,
those
who
reported
eating
the
relevant
commodities
as
well
as
those
who
did
not)
basis.
In
accordance
with
HED
policy,
per
capita
exposure
and
risk
are
reported
for
all
tiers
of
analysis.
However,
for
tiers
1
and
2,
significant
differences
in
user
vs.
per
capita
exposure
and
risk
are
identified
and
noted
in
the
risk
assessment.
HED
notes
that
there
is
a
degree
of
uncertainty
in
extrapolating
exposures
for
certain
population
subgroups
which
may
not
be
sufficiently
represented
in
the
consumption
surveys,
(e.
g.,
nursing
and
non
nursing
infants
or
Hispanic
females).
Therefore,
risks
estimated
for
these
subpopulations
were
included
in
representative
populations
having
sufficient
numbers
of
survey
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13
respondents
(e.
g.,
all
infants,
or
females
13
50
years).
IV.
Toxicological
Information
The
toxicological
endpoint
summary
table
below
is
from
the
HIARC
document
(01/
16/
2002,
TXR#
0050371).
The
FQPA
SF
was
obtained
from
the
committee
report
(05/
15/
2002,
TXR#
0050750).
Table
1.
Summary
of
Toxicological
Doses
and
Endpoints
for
[CHEMICAL]
for
Use
in
Dietary
Exposure
Assessment
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF*
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
[Female
13
50]
NOAEL
=
[400]
mg/
kg/
day
UF
=
[100]
Acute
RfD
=
[4.0]
mg/
kg/
day
FQPA
SF
=
[10]
aPAD
=[
0.40]
mg/
kg/
day
[Developmental
Toxicity
Rat]
LOAEL
=
[
900]
mg/
kg/
day
based
on
[decreased
fetal
weight,
malformation
of
kidneys]
Chronic
Dietary
all
populations
NOAEL=
[5]
mg/
kg/
day
UF
=
[100]
Chronic
RfD
=
[0.05]
mg/
kg/
day
FQPA
SF
=
[1]
cPAD
=[
]
=
[0.05]
mg/
kg/
day
[Chronic
One
Year
Feeding
Dog]
LOAEL
=
[
~40]
mg/
kg/
day
based
on
[hepatotoxicity]
V.
Results/
Discussion
As
stated
above,
for
acute
and
chronic
assessments,
HED's
level
of
concern
is
exceeded
when
the
dietary
risk
exceeds
100%
of
the
PAD.
The
DEEM
analyses
can
estimate
the
dietary
exposure
of
the
U.
S.
population
and
26
population
subgroups.
The
results
reported
in
Table
2
are
for
the
appropriate
subpopulation,
females
aged
13
to
50
years.
The
results
reported
in
Table
3
are
for
the
U.
S.
Population
(total),
all
infants
(<
1
year
old),
children
1
6,
children
7
12,
females
13
50,
males
13
19,
males
20+,
and
seniors
55+.
The
results
for
the
other
population
subgroups
are
included
in
the
appendices.
They
are
not
included
in
the
tables
because
the
numbers
of
respondents
in
the
other
subgroups
were
not
sufficient;
and
therefore,
the
exposure
estimates
for
these
subgroups
contained
higher
levels
of
uncertainty.
However,
the
respondents
in
these
subgroups
were
also
part
of
larger
subgroups
which
are
listed
in
the
Tables.
For
example,
nursing
and
non
nursing
infants
are
included
in
all
infants.
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Results
of
Acute
Dietary
Exposure
Analysis
Results
are
reported
at
the
95th
percentile
of
exposure
because
the
assessment
incorporated
100%
CT.
The
acute
dietary
risk
estimates
are
provided
for
the
population
subgroup
consisting
of
females
aged
13
through
50
years
only.
This
assessment
concludes
that
the
exposure
is
below
HED's
level
of
concern
for
this
subgroup.
Exposures
as
a
percentage
of
the
RfD
are
calculated
to
be
less
than
1%
at
the
95
th
percentile.
Table
2.
Results
of
Acute
Dietary
Exposure
Analysis
at
the
95
th
Percentile
of
Exposure
Population
Subgroup
aPAD
(mg/
kg/
day)
Exposure
(mg/
kg/
day)
%
aPAD
Females
13
50
years
old
0.
40
0.
003475
<1
Results
of
Chronic
Dietary
Exposure
Analysis
Table
3.
Results
of
Chronic
Dietary
Exposure
Analysis
Population
Subgroup
cPAD
(mg/
kg/
day)
Exposure
(mg/
kg/
day)
%
cPAD
U.
S.
Population
(total)
0.
05
0.
002118
4
All
Infants
(<
1
year)
0.
05
0.
003629
7
Children
1
6
years
0.
05
0.
007304
15
Children
7
12
years
0.
05
0.
003899
8
Females
13
50
0.05
0.001265
3
Males
13
19
0.05
0.002315
5
Males
20+
years
0.
05
0.
001183
2
Seniors
55+
0.05
0.001123
2
The
chronic
dietary
risk
estimates
are
provided
for
the
U.
S.
population
(total)
and
various
population
subgroups.
This
assessment
concludes
that
the
exposure
is
below
HED's
level
of
concern
for
all
population
subgroups
examined.
Exposures,
as
a
percentage
of
the
RfD,
ranged
from
approximately
3%
for
females
aged
13
through
50
years
to
15%
for
children
aged
1
through
6
years.
VII.
Conclusions
[Hexazinone]
Dietary
Exposure
Assessment
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The
Tier
1
acute
and
chronic
dietary
risk
assessments
were
conducted
for
all
supported
hexazinone
food
uses.
Dietary
risk
estimates
are
provided
for
the
U.
S.
population
(total)
and
various
population
subgroups.
This
assessment
concludes
that
for
all
supported
registered
commodities,
the
acute
risk
estimates
are
below
the
Agency's
level
of
concern
at
the
95
th
exposure
percentile
for
the
population
subgroup
consisting
of
females
aged
13
to
50
years.
The
acute
dietary
exposure
estimate
for
this
group
is
<1%
of
the
aPAD.
This
assessment
also
concludes
that
for
all
commodities,
the
chronic
risk
estimates
are
below
the
Agency's
level
of
concern
for
the
U.
S.
population
(total)
(4%
of
the
cPAD)
and
all
population
subgroups.
The
most
highly
exposed
population
subgroup
is
children
aged
1
to
6
years.
The
chronic
dietary
exposure
estimate
for
the
highest
exposed
population
subgroup
is
15%
of
the
cPAD.
[Hexazinone]
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Apendix
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
Chronic
analysis
for
HEXAZINONE
(1989
92
data)
Residue
file
name:
C:\
deem\
hexazinone_
nopork.
RS7
Adjustment
factor
#2
used.
Analysis
Date
05
15
2002/
12:
57:
29
Residue
file
dated:
05
15
2002/
12:
12:
42/
8
Reference
dose
(RfD,
Chronic)
=
.05
mg/
kg
bw/
day
===============================================================================
Total
exposure
by
population
subgroup
Total
Exposure
Population
mg/
kg
Percent
of
Subgroup
body
wt/
day
Rfd
U.
S.
Population
(total)
0.002118
4.2%
U.
S.
Population
(spring
season)
0.002129
4.3%
U.
S.
Population
(summer
season)
0.002075
4.2%
U.
S.
Population
(autumn
season)
0.002208
4.4%
U.
S.
Population
(winter
season)
0.002060
4.1%
Northeast
region
0.002098
4.2%
Midwest
region
0.002360
4.7%
Southern
region
0.001942
3.9%
Western
region
0.002147
4.3%
Hispanics
0.002297
4.6%
Non
hispanic
whites
0.002126
4.3%
Non
hispanic
blacks
0.001914
3.8%
Non
hisp/
non
white/
non
black
0.002242
4.5%
All
infants
(<
1
year)
0.003629
7.3%
Nursing
infants
0.000963
1.9%
Non
nursing
infants
0.004751
9.5%
Children
1
6
yrs
0.007304
14.6%
Children
7
12
yrs
0.003899
7.8%
Females
13
19
(not
preg
or
nursing)
0.001791
3.6%
Females
20+
(not
preg
or
nursing)
0.001104
2.2%
Females
13
50
yrs
0.001265
2.5%
Females
13+
(preg/
not
nursing)
0.001947
3.9%
Females
13+
(nursing)
0.001973
3.9%
Males
13
19
yrs
0.002315
4.6%
Males
20+
yrs
0.001183
2.4%
Seniors
55+
0.001123
2.2%
Pacific
Region
0.002128
4.3%
[Hexazinone]
Dietary
Exposure
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DP
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of
13
Attachment
(electronic
file
id
107201accr.
rs7).
cc:
JSPunzi
(RRB2),
Hexazinone
Reg.
Std.
File,
Hexazinone
SF,
RF,
LAN.
7509C:
RRB2:
John
S.
Punzi:
CM2:
Rm
712M:
703
305
7727:
05/
15/
2002.
"hexazinone"
0.05
NEWD,
0.04
NOEL,
0
0
0
05
15
2002/
12:
12:
42
999
0
7
"01009AA","
13B",
0.3
1
1
7
"Blueberries",
""
11
Uncooked,
0.3
1
1
""
12
Cooked:
NFS,
0.3
1
1
""
13
Baked,
0.3
1
1
""
14
Boiled,
0.3
1
1
""
15
Fried,
0.3
1
1
""
31
Canned:
NFS,
0.3
1
1
""
41
Frozen:
NFS,
0.3
1
1
""
89
"06013AA","
O",
0.3
1
1
7
"Pineapples
peeled
fruit",
""
11
Uncooked,
0.3
1
1
""
12
Cooked:
NFS,
0.3
1
1
""
13
Baked,
0.3
1
1
""
14
Boiled,
0.3
1
1
""
31
Canned:
NFS,
0.3
1
1
""
33
Canned:
Baked,
0.3
1
1
""
41
Frozen:
NFS,
0.3
1
1
""
90
"06013DA","
O",
0.3
5
1
1
"Pineapples
dried",
""
18
Dried,
0.3
5
1
""
91
"06013JA","
O",
0.3
1.7
1
5
"Pineapples
juice",
""
11
Uncooked,
0.3
1.7
1
""
12
Cooked:
NFS,
0.3
1.7
1
""
14
Boiled,
0.3
1.7
1
""
31
Canned:
NFS,
0.3
1.7
1
""
42
Frozen:
Cooked,
0.3
1.7
1
""
283
"25003SA","
O",
0.6
1
1
0
"Sugar
cane",
""
284
"25003SB","
O",
4
1
1
0
"Sugar
cane/
molasses",
""
318
"50000DB","
D",
0.24
1
1
0
"Milk
nonfat
solids",
""
319
"50000FA","
D",
0.24
1
1
14
"Milk
fat
solids",
""
12
Cooked:
NFS,
0.24
1
1
""
13
Baked,
0.24
1
1
""
14
Boiled,
0.24
1
1
""
15
Fried,
0.24
1
1
""
16
Pasteurized,
0.24
1
1
""
18
Dried,
0.24
1
1
""
31
Canned:
NFS,
0.24
1
1
""
32
Canned:
Cooked,
0.24
1
1
""
34
Canned:
Boiled,
0.24
1
1
""
41
Frozen:
NFS,
0.24
1
1
""
42
Frozen:
Cooked,
0.24
1
1
""
45
Frozen:
Fried,
0.24
1
1
""
51
Cured:
NFS
(smoked/
p,
0.24
1
1
""
52
Cured:
Cooked(
smokd/,
0.24
1
1
""
320
"50000SA","
D",
0.24
1
1
14
"Milk
sugar
(lactose)",
""
12
Cooked:
NFS,
0.24
1
1
""
13
Baked,
0.24
1
1
""
14
Boiled,
0.24
1
1
""
15
Fried,
0.24
1
1
""
16
Pasteurized,
0.24
1
1
""
18
Dried,
0.24
1
1
""
31
Canned:
NFS,
0.24
1
1
""
32
Canned:
Cooked,
0.24
1
1
""
34
Canned:
Boiled,
0.24
1
1
""
41
Frozen:
NFS,
0.24
1
1
""
42
Frozen:
Cooked,
0.24
1
1
""
45
Frozen:
Fried,
0.24
1
1
""
51
Cured:
NFS
(smoked/
p,
0.24
1
1
""
52
Cured:
Cooked(
smokd/,
0.24
1
1
""
321
"53001BA","
M",
0.24
1
1
8
"Beef
meat
byproducts",
""
12
Cooked:
NFS,
0.24
1
1
""
13
Baked,
0.24
1
1
""
14
Boiled,
0.24
1
1
""
15
Fried,
0.24
1
1
""
31
Canned:
NFS,
0.24
1
1
""
41
Frozen:
NFS,
0.24
1
1
""
42
Frozen:
Cooked,
0.24
1
1
""
52
Cured:
Cooked(
smokd/,
0.24
1
1
""
322
"53001BB","
M",
0.24
1
1
3
"Beef
other
organ
meats",
""
12
Cooked:
NFS,
0.24
1
1
""
14
Boiled,
0.24
1
1
""
52
Cured:
Cooked(
smokd/,
0.24
1
1
""
323
"53001DA","
M",
0.24
1.92
1
0
"Beef
dried",
""
325
"53001KA","
M",
0.24
1
1
2
"Beef
kidney",
""
12
Cooked:
NFS,
0.24
1
1
""
15
Fried,
0.24
1
1
""
326
"53001LA","
M",
0.24
1
1
3
"Beef
liver",
""
12
Cooked:
NFS,
0.24
1
1
""
14
Boiled,
0.24
1
1
""
15
Fried,
0.24
1
1
""
327
"53001MA","
M",
0.24
1
1
13
"Beef
lean
(fat/
free)
w/
o
bones",
""
11
Uncooked,
0.24
1
1
""
12
Cooked:
NFS,
0.24
1
1
""
13
Baked,
0.24
1
1
""
14
Boiled,
0.24
1
1
""
15
Fried,
0.24
1
1
""
31
Canned:
NFS,
0.24
1
1
""
32
Canned:
Cooked,
0.24
1
1
""
33
Canned:
Baked,
0.24
1
1
""
34
Canned:
Boiled,
0.24
1
1
""
42
Frozen:
Cooked,
0.24
1
1
""
51
Cured:
NFS
(smoked/
p,
0.24
1
1
""
52
Cured:
Cooked(
smokd/,
0.24
1
1
""
59
Cured:
Dried
(smokd/,
0.24
1
1
""
328
"53002BA","
M",
0.24
1
1
0
"Goat
meat
byproducts",
""
329
"53002BB","
M",
0.24
1
1
0
"Goat
other
organ
meats",
""
331
"53002KA","
M",
0.24
1
1
0
"Goat
kidney",
""
332
"53002LA","
M",
0.24
1
1
0
"Goat
liver",
""
333
"53002MA","
M",
0.24
1
1
3
"Goat
lean
(fat/
free)
w/
o
bone",
""
12
Cooked:
NFS,
0.24
1
1
""
13
Baked,
0.24
1
1
""
14
Boiled,
0.24
1
1
""
334
"53003AA","
M",
0.24
1
1
0
"Horsemeat",
""
336
"53005BA","
M",
0.24
1
1
2
"Sheep
meat
byproducts",
""
12
Cooked:
NFS,
0.24
1
1
""
31
Canned:
NFS,
0.24
1
1
""
337
"53005BB","
M",
0.24
1
1
0
"Sheep
other
organ
meats",
""
339
"53005KA","
M",
0.24
1
1
0
"Sheep
kidney",
""
340
"53005LA","
M",
0.24
1
1
0
"Sheep
liver",
""
341
"53005MA","
M",
0.24
1
1
4
"Sheep
lean
(fat
free)
w/
o
bone",
""
12
Cooked:
NFS,
0.24
1
1
""
13
Baked,
0.24
1
1
""
14
Boiled,
0.24
1
1
""
15
Fried,
0.24
1
1
""
398
"50000WA","
D",
0.24
1
1
15
"Milk
based
water",
""
12
Cooked:
NFS,
0.24
1
1
""
13
Baked,
0.24
1
1
""
14
Boiled,
0.24
1
1
""
15
Fried,
0.24
1
1
""
16
Pasteurized,
0.24
1
1
""
18
Dried,
0.24
1
1
""
31
Canned:
NFS,
0.24
1
1
""
32
Canned:
Cooked,
0.24
1
1
""
33
Canned:
Baked,
0.24
1
1
""
34
Canned:
Boiled,
0.24
1
1
""
41
Frozen:
NFS,
0.24
1
1
""
42
Frozen:
Cooked,
0.24
1
1
""
43
Frozen:
Baked,
0.24
1
1
""
45
Frozen:
Fried,
0.24
1
1
""
52
Cured:
Cooked(
smokd/,
0.24
1
1
""
406
"06013JC","
O",
0.3
6.3
1
4
"Pineapples
juice
concentrate",
""
12
Cooked:
NFS,
0.3
6.3
1
""
31
Canned:
NFS,
0.3
6.3
1
""
33
Canned:
Baked,
0.3
6.3
1
""
41
Frozen:
NFS,
0.3
6.3
1
""
425
"56000MA","
M",
0.24
1
1
5
"Veal
lean
(fat
free)
w/
o
bones",
""
12
Cooked:
NFS,
0.24
1
1
""
13
Baked,
0.24
1
1
""
14
Boiled,
0.24
1
1
""
15
Fried,
0.24
1
1
""
31
Canned:
NFS,
0.24
1
1
""
426
"56000KA","
M",
0.24
1
1
0
"Veal
kidney",
""
427
"56000LA","
M",
0.24
1
1
0
"Veal
liver",
""
428
"56000BB","
M",
0.24
1
1
0
"Veal
other
organ
meats",
""
429
"56000DA","
M",
0.24
1.92
1
0
"Veal
dried",
""
430
"56000BA","
M",
0.24
1
1
0
"Veal
meat
byproducts",
""
| epa | 2024-06-07T20:31:42.934665 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0020/content.txt"
} |
EPA-HQ-OPP-2002-0188-0021 | Supporting & Related Material | "2002-09-16T04:00:00" | null | Quantitative
Usage
Analysis
for
Hexazinone
Case
Number:
0266
PC
Code:
107201
Date:
August
7,
2002
Analyst:
Frank
Hernandez
Based
on
available
pesticide
usage
information
for
the
years
of
1992
through
2001,
total
annual
domestic
usage
of
hexazinone
averaged
approximately
one
million
pounds
of
active
ingredient
(a.
i.)
on
about
one
million
acres
treated.
Hexazinone
is
a
herbicide
with
its
largest
markets,
in
terms
of
total
pounds
active
ingredient,
allocated
to
forestry
(55%),
alfalfa
(35%),
and
pasture/
rangeland
(7%).
Crops
with
a
high
percentage
of
total
U.
S.
planted
acres
treated
include
nurseries
(4%),
and
alfalfa
(2%).
Crops
with
less
than
1
percent
of
the
site
treated
include
berries,
other
hay,
landscape,
pasture/
rangeland,
and
sugarcane.
Acres
Pounds
A.
I.
Application
Rate
Planted
Treated
1,000
%
1,000
lbs.
a.
i./
A
Alfalfa
25,000
500
2
350
0.7
Berries
100,000
11
<1
10
0.9
Forestry
50,000
400
1
550
1.4
Hay,
Other
33,000
24
<1
8
0.3
Landscape
30,000
5
<1
10
2.0
Nurseries
400
15
4
10
0.7
Pasture/
Rangeland
90,000
77
<1
70
0.9
Sugarcane
1,000
2
<1
1
0.5
1,034
1,009
SOURCES:
EPA
data,
USDA,
and
National
Center
for
Food
and
Agricultural
Policy
| epa | 2024-06-07T20:31:42.938686 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0021/content.txt"
} |
EPA-HQ-OPP-2002-0188-0022 | Supporting & Related Material | "2002-09-16T04:00:00" | null | TXR#
0051040
TXR#
0051040
August
12,
2002
August
12,
2002
OFFICE
OF
PREVENTION,
PESTICIDES
AND
MEMORANDUM:
TOXIC
SUBSTANCES
Subject:
107201:
The
Revised
Toxicology
Chapter
for
the
TRED
for
Hexazinone.
DP
Barcode:
D275620
Submission:
S598837
ReReg
Case#
0266
CAS#:
51235
04
02
From:
David
G
Anderson
RRB
2
HED
(7509C)
To:
Carol
Christensen,
Risk
Assessor
RRB
2
HED
(7509C)
Thru:
Alan
Nielsen,
BSS
RRB
2,
HED
(7509C)
cc
Pauline
Wagner
The
Revised
Toxicology
Chapter
for
the
Tolerance
Reassessment
Evaluation
Decision
(TRED)
for
Hexazinone
is
attached.
The
old
developmental
toxicity
in
rabbits,
which
was
considered
a
data
gap
has
been
replaced
by
a
new
acceptable
developmental
toxicity
study
in
rabbits.
The
results
from
a
new
3
rd
HIARC
report
and
a
new
2
nd
FQPA
Safety
Committee
report
have
been
included.
1
Hexazinone
PC
Code:
107201
Toxicology
Disciplinary
Chapter
for
the
Tolerance
Reassessment
Evaluation
Decision
Document
Date
completed:
August
12,
2002
Prepared
for:
Health
Effects
Division
Office
of
Pesticide
Programs
U.
S.
Environmental
Protection
Agency
Arlington,
VA
22202
Prepared
by:
David
G
Anderson
form:
FINAL
June
21,
2000
2
TABLE
OF
CONTENTS
1.0
HAZARD
CHARACTERIZATION
........................................
3
2.0
REQUIREMENTS
.....................................................
4
3.0
DATA
GAP(
S)/
REQUIREMENT(
S)
.......................................
5
4.0
HAZARD
ASSESSMENT
...............................................
5
4.1
Acute
Toxicity
...................................................
5
4.2
Subchronic
Toxicity
...............................................
5
4.3
Prenatal
Developmental
Toxicity
......................................
8
4.4
Reproductive
Toxicity
............................................
12
4.5
Chronic
Toxicity
.................................................
14
4.6
Carcinogenicity
.................................................
15
4.7
Mutagenicity
...................................................
18
4.8
Neurotoxicity
...................................................
22
4.9
Metabolism
....................................................
23
4.10
Special/
Other
Studies
.............................................
24
5.0
TOXICITY
ENDPOINT
SELECTION
....................................
24
5.1
See
Section
9.2
for
Endpoint
Selection
Table.
...........................
24
5.2
Dermal
Absorption
...............................................
24
5.3
Classification
of
Carcinogenic
Potential
................................
24
6.0
FQPA
CONSIDERATIONS
............................................
25
6.1
Special
Sensitivity
to
Infants
and
Children
..............................
25
6.2
Recommendation
for
a
Developmental
Neurotoxicity
Study
.................
25
7.0
OTHER
ISSUES
......................................................
25
8.0
REFERENCES
.......................................................
25
Other
references
......................................................
29
9.0
APPENDICES
.....................................................
30
9.1
Toxicity
Profile
Summary
Tables
.....................................
31
9.1.1
Acute
Toxicity
Table
.......................................
31
9.1.2
Subchronic,
Chronic
and
Other
Toxicity
Tables
...................
31
9.2
Summary
of
Toxicological
Dose
and
Endpoints
..........................
36
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Page
3
of
38
1.0
HAZARD
CHARACTERIZATION
Hexazinone
is
a
herbicide
used
to
control
a
broad
spectrum
of
weeds
including
woody
plants
in
alfalfa,
rangeland,
pastures,
woodlands,
pineapple,
sugarcane
and
blueberries.
Non
crop
areas
include
ornamental
plants
and
forests.
Hexazinone
is
used
as
a
pre
emergent,
post
emergence
herbicide.
It
is
applied
by
direct
spray
to
plants
and
to
soils.
There
are
no
non
occupational
(residential)
uses.
Hexazinone
is
a
triazine
herbicide,
which
structurally
dissimilar
and
toxicology
different
from
other
triazines,
such
as
atrazine.
The
selectivity
of
triazine
herbicides
depends
on
the
plant's
ability
to
degrade
or
metabolize
the
parent
compound.
Sensitive
plants
have
limited
ability
to
metabolize
hexazinone.
Hexazinone
acts
through
inhibition
of
photosynthesis.
Rat
metabolism
studies
showed
that
hexazinone
was
rapidly
absorbed
and
excreted
and
essentially
no
difference
in
the
metabolism
of
males
and
females
at
high
or
low
dose
levels.
Almost
no
parent
hexazinone
was
recovered
in
urine
or
feces.
Two
major
metabolites
were
recovered
from
feces
and
urine,
in
addition
to
lesser
amounts
of
a
third
metabolite
and
individually
small
amounts
of
conjugated
products
from
urine.
Hexazinone
has
low
acute
toxicity
by
the
oral
(Category
III),
dermal
(Category
IV
)
and
inhalation
routes
(Category
III).
Primary
eye
irritation
is
severe,
causing
corneal
opacity
and
moderate
irritation
in
unwashed
eyes
(Category
I).
It
causes
mild
skin
irritation
and
is
classified
Category
IV
for
skin
irritation.
It
is
not
a
skin
sensitizer
in
the
Guinea
pig.
The
21
day
dermal
study
in
the
rabbit
showed
no
systemic
toxicity
and
mild
dermal
irritation
at
the
limit
dose.
Body
weight
decrement
and
liver
toxicity
were
the
most
frequent
effects
shown
in
studies
with
hexazinone.
Liver
toxicity
was
seen
in
the
chronic
dog
and
mouse
studies.
Body
weight
decrement
was
seen
in
the
chronic
rat
studies
and
the
studies
on
reproduction.
No
quantitative
or
qualitative
susceptibility
was
shown
in
the
prenatal
or
reproduction
studies.
In
a
reproduction
study,
pup
weight
decrement
occurred
at
the
same
dose
as
parental
body
weight
decrement.
No
reproductive
effects
were
seen
in
the
study
other
than
pup
weight
decrement.
The
rat
prenatal
study
showed
fetal
weight
decrement
and
possibly
renal
malformations
but
no
increased
susceptibility.
The
rabbit
study
possibly
showed
maternal
and
fetal
weight
decrement
at
the
same
dose
levels.
The
chronic
study
in
dogs
showed
severe
body
weight
decrement,
changes
in
liver
related
clinical
chemistry
values,
and
microscopic
lesions.
Body
weight
decrement
was
seen
in
a
chronic
carcinogenicity
studies
in
rats
and
mice.
Liver
toxicity
was
seen
in
mice.
The
mouse
carcinogenicity
study
showed
an
increased
trend
for
liver
carcinomas,
but
no
pair
wise
significant
increases.
The
rat
study
showed
no
carcinogenic
potential.
Based
on
these
studies
in
rats
and
mice,
hexazinone
was
classified
in
a
group
D,
not
classifiable
as
a
carcinogen.
Hexazinone
is
clastogenic
in
one
in
vitro
test
for
chromosomal
aberrations,
but
negative
in
the
remaining
six
other
mutagenicity
studies
including
an
in
vivo
micronucleus
test
in
mouse
bone
marrow.
The
HIARC
requested
a
28
day
inhalation
study
with
hexazinone
because
of
the
concern
for
potential
inhalation
exposure
based
on
the
use
pattern.
2.0
REQUIREMENTS
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Page
4
of
38
The
requirements
(40
CFR
158.340)
for
food
and
non
food
use
for
HEXAZINONE
are
in
Table
1.
Use
of
the
new
guideline
numbers
does
not
imply
that
the
new
(1998)
guideline
protocols
were
used.
Table
1.
Test
Technical
Required
Satisfied
870.1100
Acute
Oral
Toxicity
..............................
870.1200
Acute
Dermal
Toxicity
............................
870.1300
Acute
Inhalation
Toxicity
.........................
870.2400
Primary
Eye
Irritation
.............................
870.2500
Primary
Dermal
Irritation
..........................
870.2600
Dermal
Sensitization
..............................
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
870.3100
Oral
Subchronic
(rodent)
..........................
870.3150
Oral
Subchronic
(nonrodent)
......................
870.3200
21
Day
Dermal
...................................
870.3250
90
Day
Dermal
...................................
870.3465
90
Day
Inhalation
................................
Yes
Yes
Yes
No
1
No
2
Yes
Yes
Yes
Yes
No
870.3700a
Developmental
Toxicity
(rodent)
...................
870.3700b
Developmental
Toxicity
(nonrodent)
...............
870.3800
Reproduction
...................................
Yes
Yes
Yes
Yes
Yes
Yes
870.4100a
Chronic
Toxicity
(rodent)
.........................
870.4100b
Chronic
Toxicity
(nonrodent)
......................
870.4200a
Oncogenicity
(rat)
...............................
870.4200b
Oncogenicity
(mouse)
............................
870.4300
Chronic/
Oncogenicity
...........................
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
870.5100
Mutagenicity—
Gene
Mutation
bacterial
...........
870.5300
Mutagenicity—
Gene
Mutation
mammalian
.........
870.5375
Mutagenicity—
Structural
Chromosomal
Aberrations
.
870.
5395
Mutagenicity—
Structural
Chromosomal
Aberrations.
870.5550
Mutagenicity—
Other
Genotoxic
Effects
............
Yes
Yes
Yes
Yes
Yes
No
3
Yes
Yes
Yes
Yes
870.6100a
Acute
Delayed
Neurotox.
(hen)
....................
870.6100b
90
Day
Neurotoxicity
(hen)
........................
870.6200a
Acute
Neurotox.
Screening
Battery
(rat)
............
870.6200b
90
Day
Neuro.
Screening
Battery
(rat)
..............
870.6300
Develop.
Neuro
..................................
No
4
No
4
No
5
No
5
No
5
870.7485
General
Metabolism
..............................
870.7600
Dermal
Penetration
..............................
Yes
No
6
Yes
No
Special
Studies
for
Ocular
Effects
7
Acute
Oral
(rat)
..................................
Subchronic
Oral
(rat)
.............................
Six
month
Oral
(dog)
.............................
1
Study
not
required
by
use
pattern.
2
A
28
day
inhalation
study
was
recommended
by
the
HIARC
and
is
required.
3
Another
study
is
not
required.
4
Required
of
organophosphates
only.
5
Not
required
by
toxicity
pattern.
6
Study
is
optional.
7
Not
required
for
this
class
of
pesticides.
3.0
DATA
GAP(
S)/
REQUIREMENT(
S)
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Page
5
of
38
1.
28
Day
Inhalation
Study
(Confirmatory
study)
(Contact
Agency
before
conducting
test).
4.0
HAZARD
ASSESSMENT
4.1
Acute
Toxicity
Adequacy
of
data
base
for
acute
toxicity:
The
data
base
for
acute
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
The
acute
toxicity
data
on
HEXAZINONE
technical
is
summarized
below.
Acute
Toxicity
of
Hexazinone
Guideline
No.
Study
Type
MRIDs
#
Results
Toxicity
Category
81
1
Acute
Oral/
Rat
41235004
(1989)
LD50
=
1200
mg/
kg
III
81
2
Acute
Dermal/
Rabbit
00104974
LD50
>5278
mg/
kg
IV
81
3
Acute
Inhalation
41756701
(1991)
LC50
>
3.94
mg/
L(
4
hour)
III
81
4
Primary
Eye
Irritation
00106003
(1982)
Irreversible
corneal
opacity,
Severe
I
81
5
Primary
Skin
Irritation
00106004
(1982)
Mild
IV
81
6
Dermal
Sensitization
41235005
(1989)
NA
Not
a
skin
sensitizer
4.2
Subchronic
Toxicity
Adequacy
of
data
base
for
subchronic
toxicity:
The
data
base
for
subchronic
toxicity
is
considered
adequate
for
reregistration.
Only
a
28
day
inhalation
study
is
required
for
confirmation
at
this
time.
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Page
6
of
38
870.3100
90
Day
Oral
Toxicity
Rat
EXECUTIVE
SUMMARY:
In
this
subchronic
oral
toxicity
study
(MRID
00104977),
hexazinone
(INA
3674;
purity
not
provided;
Lot/
Batch
#
not
provided)
was
administered
in
the
diet
to
16
ChRCD
rats/
sex/
group
at
nominal
doses
of
0,
200,
1000,
or
5000
ppm
(equivalent
to
0/
0,
16.0/
16.4,
81.0/
87.3,
or
440.4/
450.7
mg/
kg
for
males/
females)
for
13
weeks.
After
4,
8,
and
13
weeks
on
the
test
diet,
10
of
the
16
rats/
sex/
dose
were
subjected
to
hematology,
clinical
chemistry,
and
urinalysis
tests.
After
13
weeks,
10
rats/
sex/
group
were
sacrificed
for
necropsy
and
histopathological
examination.
The
remaining
6
rats/
sex/
group
continued
on
the
test
diet
for
at
least
3
weeks
in
a
onegeneration
one
litter
reproduction
study.
There
were
no
treatment
related
effects
on
mortality,
clinical
signs,
food
consumption,
hematology,
urinalysis,
organ
weights,
or
histopathology.
No
data
were
provided
for
gross
pathology.
In
the
200
and
1000
ppm
animals,
all
parameters
examined
were
comparable
to
controls.
Body
weights
were
decreased
in
the
5000
ppm
animals
(94
15%)
throughout
the
study.
Likewise,
overall
body
weight
gains
(calculated
by
the
reviewers)
were
decreased
in
this
group
(98
20%).
Although
food
consumption
was
comparable
among
treated
animals
and
controls,
overall
(Days
0
91)
mean
food
efficiency
was
decreased
(statistics
not
performed)
in
the
5000
ppm
males
(911%)
and
females
(915%)
compared
to
controls.
Food
efficiency
in
males
and
females
was
unchanged
for
the
first
28
days
of
the
study.
Males
showed
a
6%
and
9%
decrement
for
days
28
56
and
days
56
91,
respectively
at
5000
ppm.
Females
showed
a
25%
and
64%
decrement
in
food
efficiency
for
the
same
respective
days.
The
progressive
nature
of
the
reduced
food
efficiency,
especially
in
females,
supports
a
body
weight
decrement
at
5000
ppm
from
toxicity.
Alanine
aminotransferase
(ALT)
was
increased
(statistics
not
performed)
in
the
5000
ppm
females
at
1
(863%),
2
(863%),
and
3
(825%)
months.
However,
because
there
were
no
treatmentrelated
changes
in
liver
weights
or
histology,
increases
in
ALT
were
considered
of
equivocal
toxicological
significance.
For
all
other
clinical
chemistry
parameters
examined,
treatment
groups
were
either
comparable
to
controls,
sporadic,
or
differences
were
not
dose
related.
Additionally,
in
the
one
generation,
one
litter
reproduction
study,
there
were
no
treatmentrelated
differences
in
pregnancy
rate
(fertility),
gestation,
number
of
pups
born,
pup
viability,
or
lactation.
However,
the
mean
pup
weight
was
lower
(924%;
statistics
not
performed)
in
the
5000
ppm
group
than
in
controls.
The
LOAEL
for
this
study
is
5000
ppm
(equivalent
to
440.4/
450.7
mg/
kg/
day
for
male/
females)
based
on
decreased
body
weights
and
food
efficiency.
The
NOAEL
is
1000
ppm
(equivalent
to
81.0/
87.3
mg/
kg/
day
for
males/
females).
The
submitted
study
is
classified
as
acceptable
does
satisfy
the
guideline
(§
82
1a;
OPPTS
870.3100)
requirements
for
a
subchronic
oral
toxicity
study
in
the
rat.
870.3100
90
Day
Oral
Toxicity
Mouse
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Page
7
of
38
No
study
is
required
or
available.
870.3150
90
Day
Oral
Toxicity
Dog
EXECUTIVE
SUMMARY:
In
this
subchronic
oral
study
(MRID
00114484),
hexazinone
INA3674
97.5%
a.
i.;
Lot/
Batch#
not
provided)
was
administered
in
the
diet
to
4
beagle
dogs/
sex/
group
at
doses
of
0,
200,
1000,
or
5000
ppm
(equivalent
to
0/
0,
5.1/
7.0,
25.9/
31.6,
122.5/
137.3
mg/
kg/
day
for
males/
females)
for
13
weeks.
Homogeneity,
concentration,
and
stability
analyses
were
not
performed
on
the
test
diets.
No
mortalities
occurred
during
the
study.
Clinical
signs
and
hematology
were
unaffected
by
the
test
substance.
At
5000
ppm,
the
negative
overall
(Weeks
0
13)
body
weight
gains
show
that
these
animals
were
unable
to
maintain
body
weight
(
0.9
kg
in
males,
0.3
kg
in
females).
Food
consumption
was
decreased
in
the
females
in
this
dose
group
at
Weeks
1
(941%)
and
2
(915%).
In
the
males,
food
consumption
was
comparable
among
treated
and
control
groups
throughout
the
study.
Findings
in
organ
weights
and
clinical
chemistry
at
5000
ppm
indicate
liver
toxicity
as
an
effect
of
treatment.
Absolute
liver
weights
were
increased
in
the
males
at
200
(810%),
1000
(821%),
and
5000
(826%)
ppm
and
in
the
females
at
5000
(833%)
ppm.
However,
relative
liver
weights
were
only
increased
at
5000
ppm
in
the
males
(827%)
and
females
(840%),
indicating
the
increases
in
absolute
liver
weights
at
200
and
1000
ppm
were
most
likely
due
to
increased
body
weights
in
these
animals
compared
to
controls.
Alkaline
phosphatase
levels
were
increased
in
the
males
and
females
in
this
dose
group
at
1
(846
75%),
2
(886
125%),
and
3
(8124
214%)
months.
Serum
levels
of
this
enzyme
increased
as
the
study
progressed.
In
the
5000
ppm
males,
proteinuria
was
observed
at
Months
2
and
3
(1/
4
each
treated
vs
0/
4
in
any
other
dose
group).
Vacuolation
of
the
cytoplasm
of
the
cells
lining
the
Loop
of
Henle
was
observed
in
the
males
(1/
4
treated
vs
0/
4
controls)
and
females
(1/
4
treated
vs
0/
4
controls)
in
this
dose
group.
The
LOAEL
was
5000
ppm
(equivalent
to
122.5/
137.3
mg/
kg/
day
in
males/
females)
based
on
decreased
body
weight
gains,
increased
relative
liver
weights,
and
increased
alkaline
phosphatase
levels
in
both
sexes
and
transiently
decreased
food
consumption
in
the
females.
The
NOAEL
for
this
study
is
1000
ppm
(equivalent
to
25.9/
31.6
mg/
kg/
day
for
males/
females).
The
submitted
study
is
classified
as
acceptable
and
does
satisfy
the
guideline
(§
82
1b;
OPPTS
870.3150)
requirement
for
a
subchronic
oral
toxicity
study
in
the
dog.
The
deficiencies
in
the
parameters
reported
did
not
appear
to
compromise
the
study
results.
870.3200
21/
28
Day
Dermal
Toxicity
–
Rabbit
EXECUTIVE
SUMMARY:
In
a
repeated
dose
dermal
toxicity
study
(MRID
41309005),
groups
of
five
male
and
five
female
New
Zealand
White
rabbits
received
applications
of
0,
50,
400,
or
1000
mg/
kg/
day
Hexazinone
technical
(>
98%,
Lot
No.
T02118994)
in
distilled
water,
6
hours/
day
for
21
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Page
8
of
38
consecutive
days.
There
were
no
treatment
related
deaths,
clinical
signs,
hematological
or
clinical
chemistry
effects,
organ
weight
effects
or
gross
or
histopathological
effects
attributable
to
treatment.
No
treatment
related
body
weight,
food
consumption,
or
food
efficiency
effects
were
observed.
Treatment
related
dermal
irritation
was
observed
on
rabbits
in
all
treatment
groups,
including
controls.
Slight
erythema
was
noted
on
3/
5
control
females,
4/
5
low
dose
males,
4/
5
low
dose
females,
and
all
mid
and
high
dose
males
and
females.
Slight
edema
was
noted
on
1/
5
control
female,
1/
5
high
dose
male,
and
1/
5
high
dose
female.
These
dermal
effects
were
not
considered
toxicologically
significant.
The
systemic
and
dermal
NOAEL
for
Hexazinone
technical
in
male
and
female
rabbits
is
the
limit
dose
of
1000
mg/
kg/
day.
The
systemic
and
dermal
LOAEL
were
not
identified.
This
study
is
classified
as
Acceptable/
Guideline
and
does
satisfy
the
guideline
requirements
for
a
repeated
dose
dermal
study
[OPPTS
870.3200
(§
82
2)]
in
rabbits.
870.3465
90
Day
Inhalation
–
Rat
No
study
is
available.
The
HIARC
determined
that
a
28
day
inhalation
study
is
required
to
address
the
concern
for
inhalation
exposure
due
in
part
to
the
irritating
properties
of
hexazinone.
The
Agency
should
be
contacted
prior
to
conducting
this
study.
A
two
page
summary
of
a
21
day
inhalation
study
has
been
submitted
(MRID#
00063972),
which
is
unacceptable
due
to
failure
to
submitted
a
complete
report
of
the
study
and
probable
unacceptable
particle
sizes.
4.3
Prenatal
Developmental
Toxicity
Adequacy
of
data
base
for
Prenatal
Developmental
Toxicity:
The
data
base
for
prenatal
developmental
toxicity
is
complete.
There
was
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
following
in
utero
exposure
to
the
acceptable
rat
study
or
the
unacceptable
rabbit
study.
In
rats,
maternal
toxicity
was
seen
at
a
lower
dose
than
developmental
toxicity,
and
in
rabbits,
developmental
effects
occurred
at
the
same
dose
level
as
maternal
toxicity.
870.3700a
Prenatal
Developmental
Toxicity
Study
Rat
EXECUTIVE
SUMMARY:
In
a
developmental
toxicity
study
(MRID
40397501),
hexazinone
(99.26%
a.
i.;
Lot#
S30306A,
Batch#
2/
36)
in
0.5%
methylcellulose
was
administered
orally
via
gavage
to
25
Crl:
CD
®
BR
female
rats/
group
at
dose
levels
of
0,
40,
100,
400,
or
900
mg/
kg
on
gestation
day
(GD)
7
through
16.
The
dosing
volume
was
10
mL/
kg
(calculated
by
reviewers).
All
dams
were
sacrificed
on
GD
22
and
their
fetuses
removed
by
cesarean
and
examined.
When
compared
to
concurrent
controls,
no
treatment
related
changes
in
clinical
signs,
gross
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Page
9
of
38
pathology,
pregnancy
rate,
live
fetuses,
resorptions,
pre
or
post
implantation
loss,
corpora
lutea,
or
implantations
were
noted
at
any
dose
level
tested.
No
treatment
related
findings
were
noted
in
the
100,
or
40
mg/
kg
groups.
In
the
900
mg/
kg
dams,
one
treatment
related
death
occurred;
alopecia
and
an
enlarged
stomach
containing
fluid
and
food
were
noted
at
necropsy.
Decreased
(p<
0.05)
body
weight
gains
were
noted
during
GDs
15
17
(937%)
and
17
22
(917%).
In
addition,
body
weight
gains
were
decreased
(p<
0.05)
for
the
overall
(GDs
7
17)
treatment
interval
(930%).
Gravid
uterine
weights
were
not
reported;
however,
adjusted
(for
gravid
uterine
weight)
terminal
body
weights
were
slightly
decreased
(96%;
p#0.05).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
GDs
9
11,
15
17,
7
17,
and
17
22.
Decreased
(p#0.05)
food
consumption
was
observed
throughout
treatment
(GDs
7
17;
916
22%)
and
post
treatment
(GDs
17
22;
99%).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
GDs
7
9,
9
11,
11
13,
13
15,
15
17,
7
17,
and
17
22.
Also
a
significantly
decreased
food
consumption
was
seen
at
400
mg/
kg/
day
(GD9
11;
91%)
and
(GD
7
17;
98%).
In
addition,
relative
(to
body)
liver
weights
were
increased
(p#0.05)
in
the
400
(5.2%)
and
900
(5.6%)
mg/
kg
dams
compared
to
concurrent
controls
(4.9%).
Decreased
(p#0.05)
terminal
body
weights
were
noted
at
900
mg/
kg
(96%).
A
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
relative
liver
weights
and
adjusted
terminal
body
weights.
In
addition,
a
significant
(p#0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
absolute
liver
weights.
Despite
this
trend,
the
observed
increases
in
absolute
liver
weights
at
100,
400,
and
900
mg/
kg
(81
8%)
were
not
statistically
significant.
Liver
weight
findings
are
considered
equivocal.
The
maternal
LOAEL
is
400
mg/
kg/
day
based
on
decreased
food
consumption
during
dosing
and
nominal
decreases
in
body
weight
gain
from
day
7
to
day
17
and
at
all
measured
intervals
between
and
at
900
mg/
kg/
day
on
mortality
and
decreased
body
weight
gains
and
food
consumption.
The
maternal
NOAEL
is
100
mg/
kg/
day.
In
the
900
mg/
kg/
day
group,
male
and
female
fetal
weights
were
decreased
(921%;
p#0.05);
a
significant
(p#0.05)
trend
by
Jonckheere's
test
was
noted
for
this
parameter.
At
400
mg/
kg/
day,
only
female
fetal
weights
were
significantly
decreased
by
2%
(insufficient
to
be
considered
an
effect).
At
necropsy,
an
increased
(p#0.05)
incidence
of
misaligned
sternebrae
(1),
a
variation,
was
observed
(fetal
incidence:
0.0217;
litter
incidence:
0.30)
relative
to
concurrent
controls
(fetal
incidence:
0.0066;
litter
incidence:
0.09).
In
addition,
an
increased
(p#0.05)
incidence
of
misaligned
sternebrae
(2+),
a
variation,
was
noted
(fetal
incidence:
0.0217;
litter
incidence:
0.30)
relative
to
concurrent
controls
(fetal
incidence:
0.0033;
litter
incidence:
0.04).
Furthermore,
an
increased
incidence
of
kidneys
with
no
papilla
was
observed
(fetal
incidence:
0.0347;
litter
incidence:
0.25)
relative
to
concurrent
controls
(fetal
incidence:
0.0062;
litter
incidence:
0.04).
Although
the
incidence
was
not
statistically
significant,
a
dose
related
trend
(p#0.05)
was
observed.
The
developmental
toxicity
LOAEL
is
900
mg/
kg/
day
based
on
decreased
male
and
female
fetal
weight,
increased
incidence
of
kidneys
with
no
papilla
(malformation),
and
an
increased
incidence
of
misaligned
sternebrae
(variation).
The
developmental
toxicity
NOAEL
is
400
mg/
kg/
day.
HEXAZINONE/
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August/
2002
TRED
Toxicology
Chapter
Page
10
of
38
The
developmental
toxicity
study
in
the
rat
is
classified
acceptable/
guideline
(OPPTS
870.3700;
§83
3
a)
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
in
the
rat.
870.3700a
Prenatal
Developmental
Toxicity
Study
Rat
EXECUTIVE
SUMMARY:
In
a
developmental
toxicity
study
(MRID
00114486),
hexazinone
(97.5%
a.
i.;
Code#
INA
3674
19,
Lot/
Batch#
N.
B.
6849
30
[6842
29];
no
further
information
provided)
was
administered
orally
in
the
diet
to
25
27
ChR
CD
female
rats/
group
at
dose
levels
of
0,
200,
1000,
or
5000
ppm
(equivalent
to
0,
18.9,
94.5,
and
482.0
mg/
kg)
on
GD
6
through
15.
All
dams
were
sacrificed
on
GD
21
and
their
fetuses
removed
by
cesarean
and
examined.
When
compared
to
concurrent
controls,
no
treatment
related
changes
in
food
consumption,
or
number
of
implantations,
live
fetuses,
dead
fetuses,
or
premature
deliveries
were
noted.
It
was
stated
that
no
treatment
related
changes
in
mortality,
clinical
signs,
or
gross
pathology
were
observed;
however
no
data
were
provided.
Gravid
uterine
weights
were
not
reported.
Sex
ratios,
the
number
of
corpora
lutea,
pre
implantation
loss,
and
post
implantation
loss
were
not
reported
and
could
not
be
calculated
without
individual
data
(not
provided).
Throughout
the
study,
standard
deviations
were
not
calculated,
individual
data
were
not
provided,
and
statistical
analyses
were
not
performed.
Mean
body
weight
gains
and
food
efficiency
were
decreased
during
treatment
(GDs
6
16).
At
5000
ppm,
mean
body
weight
gains
were
decreased
by
74%
compared
to
concurrent
controls.
In
addition,
food
efficiency
during
the
treatment
interval
was
0.84
(vs.
3.0
in
controls).
At
5000
ppm,
markedly
decreased
body
weights
were
observed
at
GDs
16
(919%)
and
21
(912%).
Additionally
at
5000
ppm,
the
number
of
females
showing
partial
resorption
(excluding
complete
resorptions)
was
56.5%.
This
incidence
exceeded
the
concurrent
control
incidence
(39.1%);
however,
it
was
within
the
range
of
historical
controls
(mean
was
40.6%,
range
was10.5
77.8%).
The
maternal
LOAEL
is
5000
ppm
(equivalent
to
482
mg/
kg/
day)
based
on
decreased
body
weights,
body
weight
gains,
and
food
efficiency.
The
maternal
NOAEL
is
1000
ppm
(equivalent
to
94.5
mg/
kg/
day).
No
treatment
related
findings
were
noted
in
the
fetuses
at
200,
1000,
or
5000
ppm.
The
developmental
toxicity
LOAEL
was
not
observed.
The
developmental
toxicity
NOAEL
is
5000
ppm
(equivalent
to
482.0
mg/
kg/
day).
This
developmental
toxicity
study
in
the
rat
is
classified
unacceptable/
upgradable
pending
submission
of
the
following
information:
Individual
maternal
and
fetal
data
Statistical
analyses
of
the
data
Environmental
conditions
of
the
testing
laboratory
Gross
pathology
data.
Sex
ratios,
the
number
of
corpora
lutea,
pre
implantation
loss,
and
post
implantation
loss
Litter
incidence
for
fetal
necropsy
findings
Clinical
signs
and
mortality
data
HEXAZINONE/
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August/
2002
TRED
Toxicology
Chapter
Page
11
of
38
870.3700b
Prenatal
Developmental
Toxicity
Study
Rabbit
EXECUTIVE
SUMMARY:
In
a
developmental
toxicity
study
(MRID
45677801)
[DXP
A3674]
hexazinone
(98.78
%
a.
i.,
batch/
lot#
DXP
A3694
329)
was
administered
to
22
female
[Hra:(
NZW)
SPF
strain]
rabbits/
group
by
gavage]
at
dose
levels
of
0,
20,
50,
125
or
175
mg/
kg
bw/
day
from
days
7
through
28
of
gestation.
Maternal
toxicity
was
demonstrated
by
statistically
significant
findings
at
125
mg/
kg/
day
of
a
body
weight
gain
decrement
of
102
g
between
gd
7
9
and
57
g
between
gd
9
11,
food
consumption
decrement
of
18%,
abortions,
death
and
clinical
signs
such
as
diarrhea,
stained
cageboard
and
tail.
Only
1
dam
and
1
litter
survived
to
termination
at
175
mg/
kg/
day.
The
maternal
LOAEL
is
125
mg/
kg
bw/
day,
based
on
body
weight
gain
decrement,
decreased
food
consumption,
abortions,
death
and
clinical
signs
including
abnormal
gait
at
175
mg/
kg/
day.
The
maternal
NOAEL
is
50
mg/
kg
bw/
day.
No
dose
related
external,
visceral
or
skeletal
findings
were
noted.
Since
only
1
dam
with
1
litter
survived
to
termination
at
the
175
mg/
kg/
day
dose,
evaluation
of
embryo/
fetal
effects
at
this
dose
are
meaningless.
Random
malformations
were
seen
in
control
and
the
highest
dose
group
with
no
dose
relationship.
Mean
male
and
female
fetal
weight
was
reduced
by
5%
and
female
fetal
weight
was
reduced
by
10%
at
125
mg/
kg/
day.
Although
this
weight
reduction
was
not
list
as
being
statistically
significant,
the
author
stated
that
this
slight
weight
reduction
at
125
mg/
kg/
day
was
a
developmental
effect
level
and
this
reviewer
agrees.
The
developmental
LOAEL
is
125
mg/
kg
bw/
day,
based
on
mean
male
and
female
fetal
weight
decrement
and
female
fetal
weight
decrement.
The
developmental
NOAEL
is
50
mg/
kg
bw/
day.
The
developmental
toxicity
study
in
the
rabbit
is
classified
acceptable
(guideline)
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
(OPPTS
870.3700;
OECD
414)
in
the
rabbit.
870.3700b
Prenatal
Developmental
Toxicity
Study
Rabbit
EXECUTIVE
SUMMARY:
In
a
developmental
toxicity
study
(MRID
00028863),
hexazinone
(100%
a.
i.;
Lot/
batch
#
E21216A)
was
administered
orally
via
gavage
in
a
dosing
volume
of
1
mL/
kg)
to
17
female
New
Zealand
White
rabbits/
group
at
dose
levels
of
0,
20,
50,
or
125
mg/
kg
on
GD
6
through
19.
All
does
(except
those
that
died
or
delivered
prematurely)
were
sacrificed
on
GD
29,
and
their
fetuses
removed
by
cesarean
and
examined.
When
compared
to
concurrent
controls,
no
treatment
related
changes
in
mortality,
clinical
signs,
body
weights,
gross
pathology,
fetal
weights,
sex
ratios,
pre
implantation
or
post
implantation
losses,
or
the
number
of
corpora
lutea,
implantations,
resorptions,
live
fetuses,
or
dead
fetuses
were
observed.
At
125
mg/
kg,
food
consumption
was
decreased
(p#0.05),
relative
to
concurrent
controls,
at
the
beginning
of
treatment
from
GD
7
through
11
(961
89%).
Decreases
in
food
consumption,
that
were
not
statistically
significant,
continued
throughout
treatment
(GDs
12
19;
92
37%).
Diminished
HEXAZINONE/
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August/
2002
TRED
Toxicology
Chapter
Page
12
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38
food
consumption
resulted
in
decreased
(not
statistically
significant)
body
weight
gains
in
the
does
241.5
g)
relative
to
concurrent
controls
(
7.2
g)
during
GDs
6
11.
However,
weight
gain
in
these
animals
recovered
quickly
and
was
higher
than
control
animals
during
subsequent
treatment
intervals
(GDs
11
15
and
15
19).
The
maternal
LOAEL
is
125
mg/
kg/
day
based
on
transient
decreases
in
food
consumption
and
body
weight
gains.
The
maternal
NOAEL
is
50
mg/
kg/
day.
At
125
mg/
kg/
day,
the
following
skeletal
variations
were
noted
(data
presented
as
fetal
incidence
vs.
0
controls):
(i)
lagging
ossification
in
extremities
(0.0882);
(ii)
malaligned
thoracic
vertebrae
(0.0294);
and
(iii)
flexed
wrist(
s)
(0.0294).
In
addition,
non
ossified
thumb,
an
anomaly,
was
noted
at
an
increased
incidence
(0.0294)
relative
to
concurrent
controls
(0).
In
the
absence
of
historical
control
data,
these
findings
are
considered
treatment
related.
In
addition,
it
could
not
be
determined
how
many
of
these
nominally
increased
incidences
were
from
different
litters,
which
would
have
increased
concern
for
developmental
toxicity.
The
developmental
toxicity
LOAEL
is
125
mg/
kg/
day,
based
on
possible
skeletal
abnormalities
and
total
abnormalies.
The
developmental
toxicity
NOAEL
is
50
mg/
kg/
day.
The
developmental
toxicity
study
in
rabbits
is
classified
unacceptable/
upgradable,
pending
submission
of
acceptable
purity,
concentration,
stability
and
litter
data
and
historical
control
data.
A
letter
dated
9/
26/
01
from
the
registrant
provided
no
additional
information
about
this
rabbit
developmental
toxicity
study
other
than
the
doses
were
not
analyzed
and
that
a
repeat
rabbit
developmental
toxicity
was
currently
being
conducted.
4.4
Reproductive
Toxicity
Adequacy
of
data
base
for
Reproductive
Toxicity:
The
data
base
for
reproductive
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
There
was
no
evidence
of
qualitative
or
quantitative
susceptibility
in
a
two
generation
study
of
reproduction.
870.3800
Reproduction
and
Fertility
Effects
Rat
Executive
Summary:
In
a
two
generation
reproduction
study,
hexazinone
(98%
a.
i.,
Lot
No.
T02118994)
was
administered
to
groups
of
30
male
and
30
female
Sprague
Dawley
rats
in
the
diet
at
concentrations
of
0,
200,
2000,
or
5000
ppm
(MRID
42066501).
One
litter
was
produced
in
the
first
generation
and
two
litters
were
produced
in
the
second
generation.
Test
substance
intake
for
the
treated
F0
groups
was
11.8,
117,
and
294
mg/
kg/
day,
respectively,
for
males
and
14.3,
143,
and
383
mg/
kg/
day,
respectively,
for
females.
Test
substance
intake
for
the
treated
F1
groups
was
15.3,
154,
and
399
mg/
kg/
day,
respectively,
for
males
and
17.7,
180,
and
484
mg/
kg/
day,
respectively,
for
females.
F0
and
F1
parental
animals
were
administered
test
or
control
diet
for
73
or
105
days,
respectively,
prior
to
mating,
throughout
mating,
gestation,
and
lactation,
and
until
necropsy.
Deaths
of
several
F0
and
F1
parental
animals
were
considered
incidental
to
treatment.
No
HEXAZINONE/
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August/
2002
TRED
Toxicology
Chapter
Page
13
of
38
treatment
related
clinical
signs
of
toxicity
were
observed
in
the
adult
animals
of
either
generation.
Gross
necropsy
was
unremarkable
and
no
microscopic
lesions
were
observed
in
selected
tissues
from
the
reproductive
tracts
of
male
and
female
parental
animals.
Body
weights
and
body
weight
gains
of
the
F0
males
were
not
affected
by
treatment.
Premating
body
weight
gains
by
the
mid
and
high
dose
F0
females
were
76%
and
62%
(p
#
0.05
for
both),
respectively,
of
the
control
level
resulting
in
final
premating
body
weights
93%
and
87%
(p
#
0.05),
respectively,
of
the
controls.
Body
weights
of
the
high
dose
F1
males
and
females
were
significantly
reduced
(p
#
0.05)
during
the
premating
interval
with
overall
weight
gains
87%
and
82%,
respectively,
of
the
control
group
amounts.
Reductions
in
body
weights
and
body
weight
gains
during
premating
for
the
mid
and
high
dose
F0
and
high
dose
F1
dams
continued
during
gestation
and
lactation.
Food
consumption
during
premating
was
similar
between
the
treated
and
control
groups
for
males
and
females
of
both
generations.
However,
during
gestation
significantly
(p
#
0.05)
lower
food
consumption
was
noted
for
the
high
dose
F1
dams
during
production
of
both
litters
and
for
the
middose
F1
dams
during
production
of
the
second
litter.
There
was
a
statistically
significant
increase
in
absolute
P0
testes
weight
that
appeared
to
be
dose
related,
but
a
nominally
decrease
absolute
F1
adult
testes
weight
in
the
5000
ppm
dose
groups.
The
F1
testes
weight
change
did
not
appear
to
dose
related.
The
testes
weight
changes
in
males
would
appear
to
be
incidental.
Therefore,
the
systemic
toxicity
LOAEL
is
2000
ppm
(117
154
mg/
kg/
day
for
males
and
143
180
mg/
kg/
day
for
females)
based
on
reduced
body
weight
and
body
weight
gains
by
F1
males
and
F0
and
F1
females.
The
systemic
toxicity
NOAEL
is
200
ppm
(11.8
15.3
mg/
kg/
day
for
males
and
14.3
17.7
mg/
kg/
day
for
females).
No
reproductive
effects
were
seen
in
the
study
except
for
the
weight
effects
on
offspring.
Live
birth
and
viability
indices
and
litter
survival
were
similar
between
the
treated
and
control
groups.
The
lactation
index
for
the
F2b
high
dose
litters
was
85.8%
(p
#
0.05)
compared
to
97.5%
for
the
control
group.
Pup
body
weights
were
decreased
throughout
lactation
in
the
mid
and
high
dose
groups
of
all
litters
as
compared
with
the
control
groups
with
statistical
significance
(p
#
0.05)
attained
at
most
time
points.
The
lower
pup
body
weights
were
more
pronounced
in
females
than
in
males.
F1
and
F2a
female
pup
weights
were
statistically
significantly
decreased
at
birth,
day
7
and
14
of
lactation
at
$2000
ppm.
There
were
no
obvious
reproductive
effects
other
than
the
pup
weight
decrement.
Therefore,
the
offspring
LOAEL
is
2000
ppm
(117
154
mg/
kg/
day
for
males
and
143
180
mg/
kg/
day
for
females)
based
on
reduced
female
pup
body
weights
at
birth
and
during
lactation.
The
reproductive
toxicity
NOAEL
was
200
ppm
(11.8
15.3
mg/
kg/
day
for
males
and
14.3
17.7
mg/
kg/
day
for
females).
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
guideline
requirements
for
a
reproductive
toxicity
study
[OPPTS
870.3800
(§
83
4)]
in
rats.
HEXAZINONE/
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August/
2002
TRED
Toxicology
Chapter
Page
14
of
38
4.5
Chronic
Toxicity
Adequacy
of
data
base
for
chronic
toxicity:
The
data
base
for
chronic
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
The
chronic
study
in
dogs
showed
severe
body
weight
decrement,
changes
in
liver
related
clinical
chemistry
values,
and
microscopic
lesions.
Body
weight
decrement
was
seen
in
a
chronic
carcinogenicity
studies
in
rats
and
mice.
Liver
toxicity
was
seen
in
mice.
870.4100a
Chronic/
Carcinogenic
Toxicity
Rat
See
Section
below
on
Carcinogenicity
study
in
rats
(870.4300
Chronic/
Carcinogenicity
in
rats).
870.4100b
Chronic
Toxicity
Dog
EXECUTIVE
SUMMARY:
In
a
one
year
chronic
toxicity
study,
hexazinone
(98%
a.
i.,
Lot
No.
T02118994)
was
administered
to
groups
of
5
male
and
5
female
beagle
dogs
in
the
diet
at
concentrations
of
0,
200,
1500,
or
6000
ppm
(MRID
42162301).
Time
weighted
average
doses
for
the
treated
groups
were
5.00,
41.24,
and
161.48
mg/
kg/
day,
respectively,
for
males
and
4.97,
37.57,
and
166.99
mg/
kg/
day,
respectively,
for
females.
All
animals
survived
to
scheduled
necropsy.
Treatment
related
clinical
signs
of
toxicity
included
the
observation
of
thinness
in
1/
5
mid
dose
males,
3/
5
high
dose
males,
and
1/
5
high
dose
females.
Body
weights
of
the
high
dose
groups
were
significantly
(p
#
0.05)
less
than
those
of
the
control
throughout
most
of
the
study.
Final
body
weights
of
the
high
dose
males
and
females
were
78%
and
67%,
respectively,
of
the
control
levels.
Food
consumption
by
the
high
dose
groups
was
slightly
(n.
s.)
less
than
that
of
the
controls
throughout
the
study
with
statistical
significance
(p
#
0.05)
attained
for
females
at
week
52.
Overall
food
consumption
(weeks
1
52)
for
high
dose
males
and
females
was
85%
(n.
s.)
and
74%
(p
#
0.05),
respectively,
of
the
control
group
levels.
Body
weights
and
food
consumption
for
the
low
and
mid
dose
groups
were
not
affected
by
treatment.
No
treatment
related
ophthalmological
lesions,
changes
in
urinalysis
parameters,
or
gross
necropsy
findings
were
noted.
A
moderate
macrocytic
anemia
was
observed
in
the
high
dose
groups
as
evidenced
by
slight
or
significant
(p
#
0.05)
decreases
in
RBC
counts,
hemoglobin,
and
hematocrit
and
increases
in
MCV
and
MCH
in
one
or
both
sexes
throughout
the
study.
Cholesterol
levels
were
significantly
(p
#
0.05)
decreased
in
the
high
dose
groups
beginning
at
week
13
for
males
(52
64%
of
controls)
and
at
week
26
for
females
(45
51%
of
controls).
Albumin
levels
were
significantly
(p
#
0.05)
decreased
in
the
mid
dose
males
(93%
of
controls)
at
week
13
only,
and
in
the
high
dose
males
(74
78%
of
controls)
and
females
(75
82%
of
controls)
throughout
the
study.
Beginning
on
week
13
or
26,
the
high
dose
groups
had
aspartate
aminotransferase
levels
140
203%
(p
#
0.05)
of
the
control
values
and
alanine
aminotransferase
levels
206
276%
(p
#
0.05)
of
the
control
values.
Alkaline
phosphatase
levels
were
significantly
(p
#
0.05)
HEXAZINONE/
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August/
2002
TRED
Toxicology
Chapter
Page
15
of
38
increased
in
the
mid
dose
males
(259
409%
of
controls)
and
females
(163
194%
of
controls;
n.
s.)
beginning
at
week
26
and
in
the
high
dose
males
(346
1363%
of
controls)
and
females
(307
559%
of
controls)
beginning
at
week
13.
For
the
high
dose
animals,
decreases
in
absolute
testes
weights
in
males
and
kidney,
heart,
and
brain
weights
in
females
(
12%)
and
increases
in
relative
liver
weights
in
males
and
females
were
considered
due
to
lower
final
body
weights
of
these
animals
as
compared
with
controls.
Microscopic
lesions
in
the
liver
of
high
dose
animals
included
concentric
membranous
bodies
in
4
males
and
5
females,
centrilobular
single
cell
necrosis
in
3
males
and
3
females,
hepatocellular
pigment
in
3
males
and
3
females,
and
vacuolation
in
3
males
and
4
females.
In
addition
vacuolation
was
observed
in
one
mid
dose
male
and
pigment
and
membranous
bodies
were
each
observed
in
one
mid
dose
female.
These
lesions
were
not
seen
in
control
or
low
dose
animals.
Therefore,
the
LOAEL
for
hexazinone
in
male
and
female
beagle
dogs
is
1500
ppm
(41.24
and
37.57
mg/
kg/
day,
respectively)
based
on
thinness
in
one
male
and
hepatotoxicity
as
evidenced
by
changes
in
clinical
chemistry
parameters
and
microscopic
lesions.
The
NOAEL
is
200
ppm
(5.00
and
4.97
mg/
kg/
day,
respectively).
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
guideline
requirements
for
a
chronic
toxicity
study
[OPPTS
870.4100
(§
83
1b)]
in
dogs.
4.6
Carcinogenicity
Adequacy
of
data
base
for
Carcinogenicity:
The
data
base
for
carcinogenicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
HED's
Carcinogenicity
Peer
Review
Committee
classified
hexazinone
as
a
Group
D
chemical
(not
classifiable
as
to
human
carcinogenicity)
(7/
27/
94).
This
classification
was
based
on
the
following
weight
of
evidence
considerations.
In
rats,
females
showed
no
evidence
for
carcinogenicity;
males
showed
a
significant
trend
only
for
thyroid
adenomas.
In
mice,
the
evidence
of
carcinogenicity
was
equivocal:
a
positive
trend
test
for
liver
tumors
was
observed
only
in
female
mice,
but
no
significant
difference
was
seen
by
pair
wise
comparison
(CPRC
Report
dated
July
27,
1994).
870.4200b
Carcinogenicity
(feeding)
Mouse
EXECUTIVE
SUMMARY:
In
this
mouse
oncogenicity
study
(MRIDs
00079203,
41359301,
42509301
and
43202901),
hexazinone
($95%
a.
i.;
Lot/
Batch
#:
H
11,
265
and
265
2)
was
administered
in
the
diet
to
CD
1
mice
(80/
sex/
group)
for
up
to
104
weeks
at
nominal
doses
of
0,
200,
2500
or
10,000
ppm
(equivalent
to
28,
366
and
1635
mg/
kg/
day
in
males
and
0,
34,
450
and
1915
mg/
kg/
day
in
females).
No
treatment
related
differences
were
observed
in
mortality,
food
consumption,
food
efficiency
or
hematology.
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38
Hepatotoxicity
was
evident
at
the
terminal
sacrifice.
Macroscopic
liver
nodule/
mass
(%
treated
vs
%
controls;
n
=
28
55)
was
observed
in
males
at
2500
(39%
vs
7%)
and
10,000
ppm
(33%).
Increased
incidences
(%
treated
vs
0%
controls;
n
=
38
55)
in
the
following
microscopic
liver
lesions
were
observed:
hyperplastic
nodule(
s)
(includes
both
foci
of
cellular
alteration
and
adenoma)
in
males
at
2500
(39%
vs
20%)
and
10,000
ppm
(36%)
and
in
females
at
10,000
ppm
(15%
vs
3%);
and
necrosis
(severity
and
type
unspecified)
in
the
10,000
ppm
males
(36%
vs
7%).
Centrilobular
hepatocyte
hypertrophy
was
observed
(%
treated
vs
%
controls)
at
the
terminal
sacrifice
(n
=
38
55)
in
males
at
2500
(18%
vs
0%)
and
10,000
ppm
(98%)
and
in
females
at
10,000
ppm
(46%
vs
0%)
and
in
the
dead
and
moribund
males
(n
=
25
40)
at
2500
(44%
vs
0%)
and
10,000
ppm
(60%).
Increased
(p#0.05
or
0.01)
liver/
gall
bladder
weights
were
observed
at
10,000
ppm
in
males
in
both
absolute
and
relative
to
body
weights
and
in
females
in
relative
to
body
weight.
Other
signs
of
toxicity
were
evident.
Distal
tail
tip
sloughing
and/
or
discoloration
was
observed
at
10,000
ppm
in
males
at
Weeks
13
104
and
in
females
at
Weeks
5
and
13
104.
Macroscopically,
tip
of
tail
missing/
sloughed
was
observed
at
the
terminal
sacrifice
in
the
10,000
ppm
males
(31%
vs
5%)
and
females
(61%
vs
11%)
and
in
the
dead
and
moribund
10,000
ppm
females
(46%
vs
2%).
The
toxicological
significance
of
these
findings
was
unclear.
Minor
decreases
(p#0.05
or
0.01)
in
body
weights
were
observed
in
the
10,000
ppm
treatment
groups
at
Weeks
13
104
in
both
sexes.
Overall
body
weight
gains
(calculated
by
the
reviewers)
were
decreased
in
the
10,000
ppm
males
(925%)
and
females
(931%).
The
LOAEL
is
2500
ppm
for
males
(equivalent
to
366
mg/
kg/
day)
based
on
gross
liver
nodules/
masses,
hyperplastic
nodules
in
the
liver
and
centrilobular
hepatocyte
hypertrophy
and
10,000
ppm
for
females
(equivalent
to
1915
mg/
kg/
day
[limit
dose])
based
on
decreased
body
weights,
increased
relative
liver/
gall
bladder
weights,
hyperplastic
nodules
and
centrilobular
hepatocyte
hypertrophy.
The
NOAEL
is
200
ppm
(equivalent
to
28
mg/
kg/
day)
for
males
and
2500
ppm
(equivalent
to
450
mg/
kg/
day)
for
females.
Liver
samples
were
first
evaluated
using
the
term
hyperplastic
nodule
which
did
not
clearly
distinguish
neoplasia
from
non
neoplasia.
Re
evaluation
was
conducted
to
make
this
distinction,
and
no
significant
differences
were
observed
between
the
treatment
groups
and
the
concurrent
controls.
However
positive
trends
(p<
0.05)
were
observed
(%
treated
vs
%
controls)
in
focus/
foci
of
cellular
alteration
in
males,
hepatocellular
neoplasm(
s)
(including
adenoma,
sarcoma,
carcinoma,
leukemia,
and
lymphoma)
in
females,
and
singular
hepatocellular
adenoma
in
females.
Focus/
foci
of
cellular
alteration
were
observed
in
males
at
2500
(11.3%
vs
5.0%)
and
10,000
ppm
(24.1%)
and
females
at
10,000
ppm
(12.5%
vs
3.8%)
beginning
at
Week
57.
Singular
hepatocellular
adenoma
was
observed
in
the
10,000
ppm
females
(7.5%
vs
2.5%)
beginning
at
Week
77.
Hepatocellular
neoplasm(
s)
were
observed
in
the
10,000
ppm
females
(8.8%
vs
2.5%).
A
carcinoma
in
the
10,000
ppm
treatment
groups
was
first
observed
at
Week
65.
The
incidence
of
carcinomas
were
within
historical
control
ranges
for
each
sex,
while
the
incidence
of
adenomas
were
increased
by
3.21%
in
the
10,000
ppm
females.
A
dose
dependent
increase
in
adenomas
was
not
observed
in
males.
The
Health
Effects
Division
Carcinogenicity
Peer
Review
Committee
(CPRC)
concluded
that
hexazinone
should
be
classified
as
a
Group
D
(not
classifiable
as
to
human
carcinogenicity)(
7/
27/
94).
Under
the
conditions
of
this
study,
evidence
of
carcinogenic
potential
was
equivocal:
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TRED
Toxicology
Chapter
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of
38
a
positive
trend
test
for
neoplasia
was
observed
in
female
mice,
but
no
significant
difference
was
determined
by
pair
wise
comparison.
The
submitted
study
is
classified
as
acceptable
for
guideline
870
4200
carcinogenicity
study
in
mice.
870.4300
Chronic/
Carcinogenicity
Study
rat
EXECUTIVE
SUMMARY:
In
this
combined
chronic/
oncogenicity
study
(MRID
00108638),
hexazinone
(94
96%
a.
i.;
Lot/
Batch
#:
6897
40
and
74.25)
was
administered
in
the
diet
to
ChR
CD
rats
(36/
sex/
group)
for
up
to
25
months
at
nominal
doses
of
0,
0,
200,
1000,
or
2500
ppm
(equivalent
to
0,
0,
10.2,
53.4,
and
138.3
mg/
kg/
day
in
males
and
0,
0,
12.5,
67.5,
and
178.6
mg/
kg/
day
in
females).
No
treatment
related
differences
were
observed
in
mortality,
clinical
signs,
food
consumption,
hematology,
clinical
chemistry,
organ
weights,
and
gross
or
microscopic
pathology.
No
adverse
effects
were
observed
in
the
200
ppm
animals.
There
were
several
signs
of
general
toxicity,
but
a
target
organ
could
not
be
clearly
identified
at
any
dose.
Terminal
body
weights
were
decreased
8%
in1000
ppm
and
20%,
p#0.05,
in
the
2500
ppm
females.
A
decrease
in
overall
body
weight
gain
(Days
0
728;
calculated
by
the
reviewers)
was
also
observed
in
the
1000
(
10%)
and
2500
ppm
(
25%)
females.
Nominal
decreases
in
body
weight
and
body
weight
gain
(
3
to
5%)
occurred
in
males
at
1000
ppm
during
the
study,
which
may
have
been
biologically
significant
at
the
end
of
the
study
(
12%
body
weight
and
14%
for
body
weight
gain).
Decreases
(p
values
not
calculated)
in
total
food
efficiency
were
observed
in
females
at
1000
(
10%)
and
2500
ppm
(
25%)
and
in
males
at
1000
ppm
during
the
study
with
overall
decrement
in
food
efficiency
in
1000
ppm
males
(
10%).
In
males
at
2500
ppm,
food
efficiency
was
depressed
for
the
first
6
months
of
the
study
(
25%),
but
from
6
months
to
the
end
of
the
study,
it
was
increased
139%.
The
reviewer
noted
problems
interpreting
the
body
weights
and
food
efficiency
in
males
at
the
top
dose
level,
which
were
not
consistent
with
the
mid
dose
level.
For
the
first
6
months
of
the
study
in
males,
a
body
weight
decrement
due
to
probable
toxicity
was
seen
at
1000
and
2500
ppm.
After
6
months
food
efficiency
in
males
at
the
1000
ppm
remained
less
than
controls
(
56%)
while
food
efficiency
at
2500
ppm
in
males
was
higher
than
controls
(+
139%)(
Table
4).
By
the
end
of
the
study,
male
body
weight
at
1000
ppm
was
12%
and
body
weight
gain
14%,
where
as
body
weight
and
body
weight
gain
in
males
at
2500
ppm
was
+3%
for
both
weight
and
gain.
The
reason
for
this
recovery
in
male
body
weight
decrement
at
2500
ppm
is
unknown,
but
it
appears
to
be
real.
[Since
absolute
and
relative
liver
weights
were
decreased
in
males
at
2500
ppm,
liver
enzyme
induction
allowing
the
recovery
seems
unproven.]
The
body
weight
decrement
at
1000
and
2500
ppm
with
recovery
in
body
weight
at
2500
ppm
indicates
the
an
adequate
dose
level
to
test
for
carcinogenicity
in
males
was
approached,
but
probably
not
attained.
Other
treatment
groups
were
similar
to
the
average
of
concurrent
controls.
Dosing
was
considered
adequate
based
on
decreased
body
weights,
body
weight
gains,
and
food
efficiency
in
the
2500
and
1000
ppm
females
and
food
efficiency
and
body
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Page
18
of
38
weights
in
the
2500
ppm
males
for
the
first
6
months.
Body
weight
(
12%)
and
body
weight
gain
14
in
males
at
1000
ppm
were
decreased
at
the
end
of
the
study,
in
addition
overall
food
efficiency
(
14%)
was
decreased
by
the
end
of
the
study.
Thus
female
body
weight
and
body
weight
gain
was
decreased
sufficiently
to
adequately
test
for
carcinogenicity.
Male
body
weight
and
body
weight
gain
at
1000
ppm
appeared
to
be
adequate
to
test
for
carcinogenicity
by
the
end
of
the
study,
but
the
lack
of
dose
response
in
male
body
weight
and
body
weight
gain
at
2500
ppm
(showing
recovery
after
6
months
such
that
body
weight
and
body
weight
gain
were
higher
than
control
values)
may
indicate
problems
with
the
interpretation
of
the
body
weights
and
body
weight
gains
at
1000
ppm.
In
the
2500
ppm
males,
creatinine
was
increased
(NS)
in
the
urine
at
months
18
and
24
and
bilirubin
was
detected
at
month
18
and
24.
The
Sponsor
reported
that
the
urine
was
more
alkaline
in
the
2500
ppm
treatment
groups
(data
not
reported).
Also
at
2500
ppm,
decreased
(p#0.05)
absolute
and
relative
liver
and
kidney
organ
weights
were
observed
in
the
males
and
increased
(p#0.05)
relative
(to
body)
stomach
and
kidney
organ
weights
were
observed
in
the
females.
However,
histopathological
data
did
not
corroborate
these
findings.
The
LOAEL
is
1000
ppm
for
males
and
females
(equivalent
to
53.3
for
males
and
67.5
mg/
kg/
day
for
females)
based
on
decreased
body
weight
and
food
efficiency
in
males
and
females.
In
males
at
2500
ppm
the
body
weight
decrement
and
food
efficiency
decrement
occurred
only
for
the
first
6
months
of
the
study.
The
NOAEL
is
200
ppm
for
males
and
females
(10.2
for
males
and
12.5
mg/
kg/
day
for
females).
Neoplasm
data
were
evaluated
by
two
pathologists.
An
increase
incidence
of
thyroid
Ccell
adenomas
was
observed
in
the
2500
ppm
males,
but
when
analyzed
by
the
Fisher's
exact
test
(p>
0.10)
or
life
table
methods
(p>
0.20)
no
significant
differences
were
observed
between
controls
and
treated
groups.
Using
life
table
analyses
a
significant
(p<
0.05)
dose
response
trend
was
observed
in
thyroid
C
cell
tumors
in
only
one
of
the
two
pathology
reports.
Female
rats
did
not
show
any
potential
for
C
cell
thyroid
adenomas.
The
incidence,
malignancy
and
latency
of
tumors
were
comparable
among
control
and
treated
rats
of
both
sexes.
Under
the
conditions
of
this
study,
carcinogenic
potential
of
hexazinone
is
considered
negative.
The
submitted
study
is
classified
as
acceptable
for
guideline
870.4300
combined
chronic/
carcinogenicity
study
in
rats.
4.7
Mutagenicity
Adequacy
of
data
base
for
Mutagenicity:
The
data
base
for
Mutagenicity
is
considered
adequate
based
on
pre
1991
mutagenicity
guidelines.
The
lack
of
an
acceptable
in
vitro
reverse
mutation
study
is
mitigated
by
an
acceptable
in
vivo
mutation
study,
and
adequate
carcinogenicity
studies.
Hexazinone
was
found
to
be
positive
for
mutagenicity
in
one
chromosomal
aberration
assay
HEXAZINONE/
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August/
2002
TRED
Toxicology
Chapter
Page
19
of
38
(in
vitro
cytogenics)
(MRID#
00130709),
but
negative
in
the
remaining
studies.
It
is
concluded
that
the
test
material
was
clastogenic
in
both
of
the
non
activated
trials
and
was
also
clastogenic
in
the
one
adequate
S9
activated
trials.
Under
both
test
conditions,
concentrations
providing
evidence
of
clastogenicity
induced
an
acceptable
level
of
cytotoxicity
(>
50%
relative
cell
survival).
Thus,
the
findings
can
not
be
considered
to
be
a
secondary
effect
of
cytotoxicity.
Nevertheless,
the
outcome
of
the
induced
structural
damage
(i.
e.,
primarily
chromatid
and
chromosome
breaks)
is
unclear
since
these
types
of
structural
aberrations
would
not
likely
be
passed
on
to
daughter
cells.
Because
unambiguous
positive
results
were
achieved,
it
was
concluded
that
the
study
provided
adequate
evidence
that
INA3674
112
(hexazinone,
technical)
is
clastogenic
in
an
acceptable
study.
Gene
Mutation
4.7.1
Guideline
870.5100,
Reverse
mutation
in
Salmonella
EXECUTIVE
SUMMARY:
In
a
reverse
gene
mutation
assay
in
bacteria
(MRID
40826201),
strains
TA98,
TA100,
TA1535,
TA1537
and
TA1538
of
S.
typhimurium
were
exposed
to
S
triazine2,4
1H,
3H)
dione,
3
cyclohexyl
6
dimethylamino
1
methyl
(95%
a.
i.)
in
ethanol
at
concentrations
of
200,
400,
600,
800
and
1000
:g/
plate
without
mammalian
metabolic
activation
(S9
mix)
and
at
concentrations
of
400,
800,
1200,
1600
and
2000
:g/
mL
with
S9
mix.
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
male
Crl:
CD(
SD)
BR
rat
liver.
The
maximum
concentrations
of
S
triazine
2,4(
1H,
3H)
dione,
3
cyclohexyl
6
dimethylamino
1
methyl
tested
produced
little
or
no
cytotoxicity,
were
not
limited
by
solubility
and
were
not
a
limit
dose
for
the
assay.
No
statistically
significant
increases
in
the
number
of
revertants
per
plate
or
positive
linear
dose
response
were
seen.
The
solvent
and
positive
controls
induced
acceptable
responses
in
the
corresponding
strains.
There
was
no
evidence
of
induced
mutant
colonies
over
background.
This
study
is
classified
as
Unacceptable.
It
does
not
satisfy
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5100
(§
84
2)]
for
in
vitro
mutagenicity
[bacterial
reverse
gene
mutation]
data
and
should
have
used
higher
doses.
4.7.2
Guideline
870.5300,
Gene
mutation
at
HGPRT
locus
EXECUTIVE
SUMMARY:
In
a
mammalian
cell
gene
mutation
assay
at
the
HGPRT
locus
(MRID
No.
00076956),
Chinese
hamster
CHO
K1
BH4
cells
cultured
in
vitro
were
exposed
to
INA
3674
112,
(Lot
No.
7612
5E6E,
95%
a.
i.)
in
ethanol
in
two
trials.
Concentrations
used
in
Trial
1
were
2.0,
11.1,
13.1,
13.9
and
14.3
mM
under
nonactivated
conditions
and
concentrations
of
2.0,
7.9,
8.9,
9.3
and
9.9
mM
under
activated
conditions
(S9
mix).
Concentrations
used
in
Trial
2
were
2.0,
5.9,
11.1,
13.1
and
13.9
mM
without
S9
mix
and
concentrations
of
2.0,
7.9,
8.9,
9.3
and
9.9
mM
with
S9
mix.
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Page
20
of
38
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
male
Charles
River
CD®
rat
livers.
INA
3674
112
was
tested
up
to
cytotoxic
concentrations.
In
Trial
1,
the
cultures
treated
at
14.3
mM
were
not
plated
for
mutation
determination
due
to
cytotoxicity
and
in
both
Trials
1
and
2,
those
cultures
treated
at
13.9
mM
were
excluded
from
analysis
because
no
mutants
were
seen.
No
statistically
significant
increases
in
mutant
frequency
over
solvent
control
values
were
seen
with
or
without
S9
mix
in
either
Trial
1
or
2.
The
expected
marked
increase
in
the
mutation
were
seen
with
the
positive
controls.
There
was,
however,
no
indication
that
INA
3674
112
induced
a
mutagenic
effect
either
in
the
presence
or
the
absence
of
S9
activation.
This
study
is
classified
as
acceptable.
It
satisfies
the
requirement
for
FIFRA
Test
Guideline
OPPTS
[870.5300
(§
84
2)]
for
in
vitro
mutagenicity
(mammalian
forward
gene
mutation)
data.
4.7.3
Guideline:
870.5375:
In
vitro
mammalian
cytogenics
(chromosomal
aberrations)
in
Chinese
hamster
CHO
cells.
EXECUTIVE
SUMMARY:
In
a
mammalian
cell
cytogenetics
assay
(MRID
No.
00130709),
Chinese
hamster
ovary
CHO
K1
BH4
cell
cultures
were
exposed
to
INA
3674
112
(Hexazinone,
95%
a.
i.)
in
ethanol
in
two
separate
trials.
Exposure
was
for
two
hours
with
activation
and
for
10
hours
without
activation.
Cells
were
harvested
10
hours
after
the
start
of
treatment.
In
Trial
1,
cells
were
treated
at
concentrations
of
1.58,
3.94,
15.85
and
19.82
mM
without
metabolic
activation
(S9
mix)
and
at
concentrations
of
0.32,
3.17,
7.93
and
15.85
mM
with
S9
mix.
In
Trial
2,
cells
were
treated
at
concentrations
of
1.58,
3.94,
7.93
and
15.85
without
S9
mix
and
at
concentrations
of
0.32,
3.17,
7.93
and
15.85
mM
with
S9
mix.
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
CD
rat
livers.
INA
3674
112
was
tested
up
to
cytotoxic
concentrations.
Based
on
the
results
of
a
preliminary
cytotoxicity
test,
upper
concentrations
of
23.78
mM
without
S9
mix
and
47.56
mM
with
S9
mix
were
selected
for
the
first
cytogenetic
assay
but
these
concentrations
proved
excessively
cytotoxic
and
were
not
scored
for
chromosomal
aberrations.
Without
S9
activation,
statistically
significant
increases
(p<
0.01)
in
structural
aberrations
per
cell
(excluding
gaps),
lesions
per
cell
and
percent
abnormal
cells
were
seen
at
15.85
mM
(Trials
1
and
2)
and
19.82
mM
(tested
in
Trial
1
only).
Relative
percent
survival
(RPS)
at
this
level
was
.50%.
The
percent
abnormal
cells
averaged
over
all
cultures
from
both
trials
was
28.0%
and
21.5%
at
19.82
and
15.85
mM,
respectively,
compared
to
the
solvent
control
values
of
2.0%
(0.5%
ethanol
in
Trial
2)
and
7.0%
(0.75%
ethanol
in
Trial
1).
The
percent
abnormal
cells
in
positive
control
cultures
was
18%
in
both
Trial
1
(4.83
mM
EMS)
and
Trial
2
(6.44
mM
EMS).
In
the
presence
of
S9
mix,
no
statistically
significant
increases
in
chromosomal
aberration
induction
were
seen
in
Trial
1;
however,
very
low
positive
control
values
indicated
a
problem
with
the
S9
mix.
Statistically
significant
increases
were
seen
at
15.85
mM
in
Trial
2;
RPS
at
15.85
mM
was
75%.
There
was
a
statistically
significant
dose
related
trend
for
all
three
parameters.
The
statistically
significant
(p
<0.01)
increases
at
15.85
mM
remained
when
the
data
from
Trial
1
and
2
were
combined
(average
of
20%
abnormal
cells
compared
to
10%
for
the
solvent
control).
The
predominant
aberrations
with
or
without
S9
mix
were
chromatid
and
isochromatid
breaks.
Solvent
and
positive
controls
(except
the
positive
control
in
Trial
1
with
S9
mix)
induced
the
appropriate
responses.
INA
3674
112
was
positive
for
the
induction
of
structural
chromosomal
aberrations
in
both
the
HEXAZINONE/
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August/
2002
TRED
Toxicology
Chapter
Page
21
of
38
presence
and
absence
of
S9
mix.
This
study
is
classified
as
Acceptable/
guideline
and
satisfies
the
requirement
for
FIFRA
Test
4.7.4
Guideline
870.5385:
In
vivo
cytogenics
assay
in
rat
bone
marrow
cells
EXECUTIVE
SUMMARY:
In
a
mammalian
cell
cytogenetics
assay
(MRID
00131355),
in
bone
marrow
cells
of
Sprague
Dawley
CD
rats,
three
rats/
dose/
sex/
harvest
time
were
exposed
to
H#
14,555
in
corn
oil
(
assumed
100%
a.
i.)
at
doses
of
100,
300
and
1000
mg/
kg
by
oral
gavage.
Bone
marrow
cells
were
harvested
at
6,
12,
24
and
48
hours
post
treatment.
The
highest
dose
tested
(1000
mg/
kg)
was
lethal.
A
major
limitation
of
this
study
was
the
number
of
animals
treated
and
the
number
of
cells
analyzed
per
animal.
At
most,
three
rats/
sex/
dose/
harvest
time
were
treated
with,
at
most,
50
cells
per
rat
analyzed.
Few
or
no
analyzable
cell
were
available
from
many
rats.
Positive
control
values
were
significantly
(p=
0.03)
increased.
There
was
no
evidence
that
H#
14,
14,555
induced
an
increase
in
the
incidence
of
chromosomal
aberrations
in
the
bone
marrow
cells
of
treated
animals.
This
study
is
classified
as
Unacceptable.
The
number
of
cells
analyzed
and
the
number
of
rats
treated
was
insufficient.
The
study
does
not
satisfy
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5385
(§
84
2)]
for
in
vivo
cytogenetic
mutagenicity
data.
4.7.5
Guideline
870.5395:
Micronucleus
assay
in
mouse
bone
marrow
EXECUTIVE
SUMMARY:
In
a
Crl:
CD
1
(ICR)
BR
mouse
bone
marrow
micronucleus
assay
(MRID
45124401),
5
mice/
sex/
dose/
harvest
time
were
treated
orally
with
Hexazinone
25L
(Lot
No.
9912033,
25%
Hexazinone
a.
i.
(24.5%
by
analysis)
and
75%
inert
ingredients)
at
doses
of
1000,
2000
and
3000
mg/
kg.
Bone
marrow
cells
were
harvested
at
24
and
48
hours
post
treatment
and
examined
for
micronucleated
polychromatic
erythrocytes
(MPCEs).
The
vehicle
was
Milli
Q
®
water.
Signs
of
toxicity
noted
at
3000
mg/
kg
included:
death,
convulsions,
half
shut
eyes,
head
tilt,
irregular
respiration,
lethargy,
low
carriage,
pallor,
prostration,
uncontrollable
spinning,
shovel
nosing,
straining
up
on
toes
and
tremors.
Micronuclei
were
scored
in
bone
marrow
from
mice
treated
at
3000
mg/
kg
and
from
the
solvent
and
positive
controls.
Mice
from
the
two
lower
dose
groups
were
not
evaluated
for
micronuclei
induction.
No
statistically
significant
increases
in
the
frequency
of
MPCEs
or
in
the
PCE/
NCE
ratio
over
the
solvent
control
values
were
seen
in
either
sex
at
either
the
24
or
48
hour
harvest
time.
The
solvent
and
positive
control
values
were
appropriate
and
within
the
testing
laboratory's
historical
control
ranges.
There
was
no
evidence
that
Hexazinone
25L
induced
a
clastogenic
or
aneugenic
effect
in
bone
marrow
at
any
harvest
time.
This
study
is
classified
as
Acceptable/
Guideline.
It
satisfies
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5395
(§
84
2)]
for
in
vivo
cytogenetic
mutagenicity
data.
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Page
22
of
38
4.7.6
Guideline
8760.5550:
Unscheduled
DNA
synthesis
assay
in
rat
hepatocytes
EXECUTIVE
SUMMARY:
In
an
unscheduled
DNA
synthesis
assay
(MRID
00130708),
primary
rat
hepatocyte
cultures
were
exposed
to
INA
3674
112
(Lot
No.
7612
5E6E,
95%
a.
i.)
in
ethanol
for
18
hours
at
concentrations
of
1
x
10
5
,
1
x
10
4
,
1
x
10
3
,
1
x
10
2
,
0.1,
1.0,
10.0
and
30.0
mM
in
Trial
1
and
at
concentrations
of
1
x
10
5
,
1
x
10
4
,
1
x
10
3
,
1
x
10
2
,
0.1,
1.0,
5.0,
10.0
and
30.0
mM
in
Trial
2.
INA
3674
112
was
tested
up
to
the
highest
achievable
concentration
in
the
solvent.
Two
slides
per
dose,
25
cells
per
slide
were
evaluated
for
UDS
induction
in
Trial
1.
One
slide
per
dose,
25
cells
per
slide
were
evaluated
in
Trial
2.
The
author
did
not
report
that
the
slides
were
coded
prior
to
analysis.
The
average
net
nuclear
grain
counts
of
test
material
treated
cells
in
Trial
1
were
all
less
than
zero
with
the
exception
of
one
slide
at
1
x
10
5
mM
(0.1
±
9.6)
and
one
slide
at
1.0
mM
(1.6
±
5.2).
The
average
net
nuclear
grain
count
was
below
zero
for
all
test
material
concentrations
in
Trial
2
with
the
exception
of
0.1
mM
where
the
average
net
nuclear
grain
count
was
0.0
±
2.9.
The
criterion
for
a
positive
response
was
an
average
net
nuclear
grain
count
of
at
least
five
in
two
experiments
at
any
tested
concentration.
The
results
were
thus
negative.
The
number
of
cells
in
repair
was
not
reported.
The
solvent
and
positive
(DMBA)
controls
induced
the
appropriate
responses.
There
was
no
evidence
that
unscheduled
DNA
synthesis,
as
determined
by
radioactive
tracer
procedures
[nuclear
silver
grain
counts]
was
induced.
This
study
is
classified
as
Acceptable/
Guideline.
It
satisfies
the
requirement
for
FIFRA
Test
Guideline;
OPPTS
870.5550
[§
84
2]
for
other
genotoxic
mutagenicity
data.
Compliance
statements
were
not
provided.
4.8
Neurotoxicity
Adequacy
of
data
base
for
Neurotoxicity:
No
neurotoxicity
data
are
required.
870.6100
Delayed
Neurotoxicity
Study
Hen
Study
is
not
required
of
hexazinone,
which
is
not
an
organophosphate.
870.6200
Acute
Neurotoxicity
Screening
Battery
Study
not
required
870.6200
Subchronic
Neurotoxicity
Screening
Battery
Study
not
required.
HEXAZINONE/
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TRED
Toxicology
Chapter
Page
23
of
38
870.6300
Developmental
Neurotoxicity
Study
Study
not
required.
4.9
Metabolism
Adequacy
of
data
base
for
metabolism:
The
data
base
for
metabolism
is
considered
to
be
complete.
No
additional
studies
are
required
at
this
time.
870.7485
Metabolism
Rat
EXECUTIVE
SUMMARY:
A
metabolism
study
(MRID
00109237
&
00140162)
was
conducted
to
evaluate
the
absorption,
distribution,
metabolism,
and
excretion
of
hexazinone
in
male
and
female
CD
rats.
Radiolabeled
(
14
C
at
position
2
or
4
on
the
cyclohexyl
ring)
hexazinone,
(Lot
#
not
reported,
purity
>95%,
radiochemical
purity
>99%)
was
administered
by
gavage
to
groups
of
one
male
and
one
female
rat
at
concentrations
of
14
mg/
kg
or
1000
mg/
kg.
A
third
group
of
two
male
and
two
female
rats
received
unlabeled
hexazinone
(~
5
mg/
kg/
day)
in
the
diet
for
three
weeks
before
being
given
a
single
14
mg/
kg
radiolabeled
gavage
dose.
Mass
balance
was
excellent
and
ranged
from
95
102%
recovery
for
all
treatment
groups.
Based
on
the
amount
of
radiolabel
recovered
in
the
urine
and
cage
wash,
absorption
of
the
test
material
was
at
least
83%
with
no
dose
or
sex
dependent
differences
noted.
By
72
hours
after
treatment,
essentially
none
of
the
radiolabeled
test
material
was
present
in
the
tissues.
Urine
was
the
primary
route
of
elimination
accounting
for
~83%
of
the
administered
dose.
Urinary
elimination
was
rapid
and
~96%
complete
within
48
hours
of
treatment.
No
apparent
sex
or
dose
related
differences
were
found.
Fecal
excretion
was
a
minor
route
of
elimination,
accounting
for
~16%
of
the
dose
and
was
rapid
with
~95%
occurring
within
72
hours
of
treatment.
Once
again,
no
apparent
sex
or
dose
related
differences
were
found.
Essentially
none
of
the
parent
compound
was
found
in
the
urine
(-83%
of
dose)
or
feces
(-16%
of
dose)
of
male
and
female
rats
following
multiple
low
dose
or
a
single
high
dose
treatment
with
hexazinone.
(Molecular
structures
of
the
parent
and
metabolites
can
be
found
in
Section
IV,
Appendix.)
3(
4
hydroxycyclohexyl)
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
(metabolite
A)
and
3(
4
hydroxycyclohexyl)
6(
methylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
(metabolite
C)
comprised
~66
and
28%,
respectively,
of
the
identified
fecal
metabolites
in
males
and
females.
These
two
metabolites
resulted
from
hydroxylation
of
the
cyclohexyl
ring
and
differed
only
by
the
metabolic
conversion
of
the
6
dimethyl
amine
to
a
secondary
methyl
amine.
No
sex,
or
dose
related
differences
in
the
formation
and
excretion
of
these
metabolites
were
found.
Three
metabolites
were
identified
in
the
urine
of
males
and
females
(metabolite
A
and
C,
-57%
and
-28%
of
identified
metabolites,
respectively)
.
Two
of
the
metabolites
were
identical
to
those
found
in
the
feces
.
The
third
metabolite
(3(
cyclohexyl)
6(
methylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione)
(metabolite
B,
-9%
of
urinary
metabolites)
resulted
from
demethylation
of
HEXAZINONE/
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August/
2002
TRED
Toxicology
Chapter
Page
24
of
38
the
6
dimethyl
amine
group
to
form
a
secondary
amine
without
hydroxylation
of
the
4
position
on
the
cyclohexyl
ring.
Approximately
3%
of
the
urine
metabolites
were
unidentified
polar
compounds
and
5%
were
isolated
from
the
hydrolyzed
urine,
suggesting
they
had
undergone
glucuronide
or
sulfate
conjugation.
No
differences
between
the
sexes
or
dose
groups
in
the
metabolic
conversion
of
hexazinone
were
found.
This
metabolism
and
disposition
study
with
rats
is
considered
Acceptable/
Nonguideline
and
does
satisfy
the
requirements
for
a
Metabolism
and
Pharmacokinetics
Study
[OPPTS
870.7485
(§
85
1)].
Major
deficiencies
include
the
use
of
1
2
male
and
female
rats/
group;
no
submission
of
test
material
lot
numbers,
stability,
or
dose
confirmation
data;
and
study
dates.
4.10
Special/
Other
Studies
None
available.
5.0
TOXICITY
ENDPOINT
SELECTION
5.1
See
Section
9.2
for
Endpoint
Selection
Table.
5.2
Dermal
Absorption
No
dermal
absorption
study
is
available.
For
dermal
absorption,
the
NOAEL
from
the
21
day
dermal
toxicity
study
(MRID
41309005)
at
the
limit
dose
of
1000
mg/
kg/
day
was
considered
a
lower
bound
for
the
LOAEL,
which
was
compared
with
the
LOAEL
of
125
mg/
kg/
day
from
the
rabbit
developmental
toxicity
study
(MRID
45677801).
The
ratio
of
these
two
numbers
was
used
to
estimate
a
dermal
absorption
factor
of
12.5%.
Dermal
Absorption
Factor:
12.5
%
5.3
Classification
of
Carcinogenic
Potential
5.3.1
Conclusions
There
was
no
evidence
of
treatment
related
tumors
in
chronic
rat
studies
and
insufficient
evidence
in
mouse
studies.
5.3.2
Classification
of
Carcinogenic
Potential
The
RfD/
Peer
Review
Committee
has
classified
hexazinone
as
a
group
D
chemical;
no
evidence
of
carcinogenicity
in
rats
and
in
mice
insufficient
evidence
of
human
carcinogenic
potential.
5.3.3
Quantification
of
Carcinogenic
Potential
HEXAZINONE/
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2002
TRED
Toxicology
Chapter
Page
25
of
38
Not
required.
6.0
FQPA
CONSIDERATIONS
6.1
Special
Sensitivity
to
Infants
and
Children
There
was
no
evidence
of
quantitative
or
qualitative
postnatal
susceptibility
in
a
twogeneration
study
of
reproduction.
There
was
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
following
in
utero
exposure
to
rats
or
rabbits
in
developmental
toxicity
studies.
In
rats,
developmental
toxicity
was
seen
at
the
highest
dose
level
tested,
and
in
rabbits,
developmental
effects
were
seen
at
the
same
dose
showing
maternal
toxicity.
6.2
Recommendation
for
a
Developmental
Neurotoxicity
Study
No
neurotoxic
potential
was
seen
in
any
of
the
studies.
A
developmental
neurotoxicity
study
is
not
required.
7.0
OTHER
ISSUES
None
8.0
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00028863.
Unknown
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in
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du
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Newark,
DE.
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201
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J.
W.
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477
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published
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1978
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352
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McCooey,
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T.,
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Krahn,
D.
F.
(1980).
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Toxicology
and
Industrial
Medicine,
Elkton
Road,
Newark,
DE
19711.
Haskell
Laboratory
Report
No.:
56
81,
MR
No.:
0581
865,
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December
1,
1980.
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00079203.
Unknown
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Two
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International
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Development
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MI.
Laboratory
Project
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HLO414
81,
June
23,
1981.
Unpublished.
MRID
00104974
Morrow,
R.
(1973)
Skin
Absorption
Toxicity
ALD
and
Skin
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Test:
Haskell
Laboratory
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No.
503
73.
(Unpublished
study
received
Dec
5,
1973
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352
EX
85;
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de
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&
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DE
MRID
00104977.
Sherman,
H.
et.
al.
(1973)
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INA
3674.
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235
73,
May
21,
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Unpublished.
MRID
00106003
Dashiell,
O.;
Henry,
J.
(1982)
Eye
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Test
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EPA
Pesticide
Registration
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3674
122]:
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Laboratory
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251
82.
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7,
1982
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352
399;
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I.
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de
Nemours
&
Co.,
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Wilmington,
DE.
MRID
00106004
Dashiell,
O.;
Hinckle,
L.
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on
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for
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Pesticide
Registration:
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Laboratory
Report
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203
82.
(Unpublished
study
received
Jul
7,
1982
under
352
399;
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E.
I.
du
Pont
de
Nemours
&
Co.,
Inc.,
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DE
MRID
00108638.
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A.
M.,
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C.
V.,
et
al.
(1977)
Long
Term
Feeding
Study
in
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with
INA
3674.
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I.
du
Pont
de
Nemours
and
Company,
Inc.,
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
Newark,
DE.
Laboratory
Project
Id.:
Haskell
Laboratory
Report
No.
353
77,
May
13,
1977.
Unpublished
MRID
00109237.
Repisarda,
C.
(1982).
Metabolism
of
14
C
labeled
hexazinone
in
the
rat.
E.
I.
duPont
de
Nemours
and
Co.,
Biochemicals
Dept.,
Research
Div.,
Experimental
Station,
Wilmington,
DE
19898.
Document
No.
AMR
79
82.
Unpublished.
MRID
00114484.
Sherman,
H.
et
al.
(1973)
Three
Month
Feeding
Study
in
Dogs
with
INA3674
E.
I.
du
Pont
de
Nemours
and
Company,
Inc.,
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
Newark,
DE.
Laboratory
Project
Id.:
Haskell
Laboratory
Report
No.
408
73,
September
12,
1973.
Unpublished.
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107201/
August/
2002
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Chapter
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27
of
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MRID
00114486.
Culik,
R.,
et
al.
(1974)
Teratogenic
Study
in
Rats
with
INA
3674.
E.
I.
du
Pont
de
Nemours
and
Company,
Inc.,
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
Newark,
DE.
Laboratory
Project
Id.:
Haskell
Laboratory
Report
No.
265
74,
April
9,
1974.
Unpublished.
MRID
00130708.
Summers,
J.
C.
(1983)
Unscheduled
DNA
Synthesis/
Rat
Hepatocytes
In
Vitro.
E.
I.
du
Pont
de
Nemours
and
Co.,
Inc.,
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
Elkton
Road,
P.
O.
Box
50,
Newark,
Delaware
19711.
Laboratory
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766
82,
MR
No.:
4508
001,
Date
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4,
1983.
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00130709.
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D.,
Irr,
J.
and
Krahn,
D.
F.(
1982)
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Vitro
Assay
for
Chromosome
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in
Chinese
Hamster
Ovary
(CHO)
Cells.
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I.
du
Pont
Nemours
and
Co.,
Inc.,
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Laboratory
for
Toxicology
and
Industrial
Medicine,
Elkton
Road,
P.
O.
Box
50,
Newark,
Delaware
19711.
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768
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001,
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00131355.
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M.
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T.
and
Zito,
M.
(1982).
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Vivo
Bone
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Cytogenetic
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in
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14,555:
Final
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Laboratories
America,
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9200
Leesburg
Turnpike,
Vienna,
Virginia
22180.
HLA
Project
number:
201
573,
December
9,
1982.
Unpublished.
MRID
00140162.
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R.
C.,
Jewell,
R.
A.,
Sherman,
H.
(No
date).
Metabolism
of
"Velpar"
weed
killer
in
the
rat.
E.
I.
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de
Nemours
and
Co.,
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Dept.,
Experimental
Station
and
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
Wilmington,
DE
19898.
No
document
or
report
number.
Results
published
in
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and
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28,
303
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40397501.
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3674
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du
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de
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and
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Inc.,
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
Newark,
DE.
Laboratory
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Laboratory
Report
No.
748
86,
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30,
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40826201.
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Russell
Jr.
and
D.
F.
Krahn
(1977).
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Evaluation
of
Striazine
2,4(
1H,
3H)
dione,
3
cyclohexyl
6
dimethylamino
1
methyl
in
Salmonella
typhimurium.
E.
I.
du
Pont
de
Nemours
and
Company,
Inc.,
Haskell
Laboratory
for
Toxicology
and
Industrial
Medicine,
Elkton
Road,
P.
O.
Box
50,
Newark,
Delaware
19714.
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Laboratory
Report
No.
588
77,
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693;
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July
29,
1977.
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J.
(1989)
Acute
Oral
Toxicity
Study
with
IN
A3674
207
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Male
and
Female
Rats:
Project
ID
347
89.
Unpublished
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prepared
by
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I.
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de
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and
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34
p.
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41235005
Pharmakon
Research
International,
Inc.
(1989)
Closed
Patch
Repeated
Insult
Dermal
Sensitization
Study
(Buehler
Method)
with
IN
A3674
207
in
Guinea
Pigs:
Project
ID
446
89.
Unpublished
study
pre
pared
by
E.
I.
du
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de
Nemours
and
Co.,
Inc.
35
p.
MRID
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Malek,
D.
(1989).
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Dose
Dermal
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21
Day
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207
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du
Pont
de
Nemours
and
Company,
Inc.,
Haskell
Laboratory
for
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and
Industrial
Medicine,
P.
O.
Box
50,
Elkton
Road,
Newark,
DE
19714.
Study
No.
HLA
673
89.
November
22,
1989.
Unpublished.
MRID
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E.
I.
(1989)
Supplement
1
to:
Two
Year
Feeding
Study
in
Mice
with
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International
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and
Development
Corporation,
Mattawan,
MI.
Laboratory
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Id.:
HLO
414
81,
November
22,
1989.
Unpublished.
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41756701
Shapiro,
R.
(1990)
Acute
Inhalation
Limit
Test:
Hexazinone,
Batch
#
GG1
15:
Lab
Project
Number:
T
452.
Unpublished
study
prepared
by
Product
Safety
Labs.
24
p.
MRID
42066501.
Mebus,
C.
A.
(1991).
Reproductive
and
fertility
effects
with
IN
A3674
207;
multigeneration
reproduction
study
in
rats.
Haskell
Laboratory,
Newark,
Delaware.
Study
No.
HLA
404
91.
September
11,
1991.
Unpublished.
MRID
42162301.
Dalgard,
D.
W.
(1991)
Chronic
toxicology
study
in
dogs
with
DPX
A3674
207
(Hexazinone).
Hazleton
Washington,
Inc.,
9200
Leesburg
Turnpike,
Vienna,
VA
22182.
Laboratory
Study
No.
201
905.
November
5,
1991.
Unpublished.
MRID
42509301.
Slone,
Jr.,
T.
W.
(1992)
Supplement
1
to:
Two
Year
Feeding
Study
in
Mice
with
Hexazinone.
E.
I.
du
Pont
de
Nemours
and
Company,
Newark,
DE.
Laboratory
Project
Id.:
HLO
414
81,
October
2,
1992.
Unpublished.
MRID
43202901.
Slone,
Jr.,
T.
W.,
(1994)
Supplement
No.
3:
Two
Year
Feeding
Study
in
Mice
with
Hexazinone.
E.
I.
du
Pont
de
Nemours
and
Company,
Newark,
DE.
Laboratory
Project
Id.:
HLO
414
81,
April
11,
1994.
Unpublished.
MRID
45124401.
Ford,
L.
S.
(2000)
Hexazinone
25L:
Mouse
Bone
Marrow
Micronucleus
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Page
29
of
38
Assay.
DuPont
Pharmaceuticals
Company,
Safety
Assessment
Section,
Stine
Haskell
Research
Center,
P.
O.
Box
30,
Elkton
Road,
Newark,
Delaware
19714
3507.
Laboratory
Project
ID:
DuPont
3852;
Company
Study
Number:
THA
00
02
47,
April
12,
2000.
Unpublished.
MRID
45677801.
Munley,
SM
(2002)
Hexazinone
(DPX
A3674)
Technical:
Developmental
Toxicity
Study
in
Rabbits.
EI
du
Pont
de
Nemours
and
Co.
Laboratory
report
number
DuPont
7405,
May
3,
2002.
Unpublished
Other
references:
U.
S.
EPA
Report:
Peer
Review
of
Hexazinone
(August
12,
1992).
U.
S.
EPA
Report:
RfD/
Peer
Review
Report
of
Hexazinone
(March
24,
1993).
U.
S.
EPA
Report:
Carcinogenicity
Peer
Review
of
Hexazinone.
(July
27,
1994).
U.
S.
EPA
Report:
Hexazinone
3
rd
Report
of
the
Hazard
Identification
Assessment
Review
Committee
(TXR#
0051033).
U.
S.
EPA
Report:
Hexazinone
2
nd
Report
of
the
FQPA
Safety
Factor
Committee
(TXR#
0051049).
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Page
30
of
38
9.0
APPENDICES
Tables
for
Use
in
Risk
Assessment
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Page
31
of
38
9.1
Toxicity
Profile
Summary
Tables
9.1.1
Acute
Toxicity
Table
Acute
Toxicity
Data
on
HEXAZINONE
Guideline
No./
Study
Type
MRID
No.
Results
Toxicity
Category
870.1100
Acute
oral
toxicity
41235004
LD50
=
1200
mg/
kg
III
870.1200
Acute
dermal
toxicity
00104974
LD50
>
5278
mg/
kg
IV
870.1300
Acute
inhalation
toxicity
41756701
(1990)
LC50
>
3.94
mg/
L(
4
hour)
III
870.2400
Acute
eye
irritation
00106003
Irreversible
corneal
opacity
I
870.2500
Acute
dermal
irritation
00106004
Mild
IV
870.2600
Skin
sensitization
41235005
Not
a
dermal
sensitizer
in
the
Buehler
test
in
Guinea
pigs
NA
9.1.2
Subchronic,
Chronic
and
Other
Toxicity
Tables
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
870.3100
90
Day
oral
toxicity
rats
0010977
(1973)
Dose:
0,
200,
1000,
5000
ppm
(equivalent
to
0,
16.0/
16.4,
81.0/
87.3,
440/
451
mg/
kg/
day,
male/
female)
Acceptable
NOAEL
=
1000
ppm
(81.0/
87.3
mg/
kg/
day
male/
female)
LOAEL
=
5000
ppm
(440/
451
mg/
kg/
day
male/
female)
based
decreased
body
weight
and
food
efficiency.
870.3150
90
Day
oral
toxicity
in
dogs
00114484
(1973)
Doses
of
0,
200,
1000,
or
5000
ppm
(equivalent
to
0/
0,
5.1/
7.0,
25.9/
31.6,
122.5/
137.3
mg/
kg/
day,
males/
females)
Acceptable
NOAEL
=
1000
ppm
(equivalent
to
25.9/
31.6
mg/
kg/
day
for
males/
females).
LOAEL
=
5000
ppm
(equivalent
to
122.5/
137.3
mg/
kg/
day
in
males/
females)
based
on
decreased
body
weight
gains,
increased
relative
liver
weights,
and
increased
alkaline
phosphatase
levels
in
both
sexes
and
transiently
decreased
food
consumption
in
the
females.
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
Page
32
of
38
870.3200
21/
28
Day
dermal
toxicity
in
rabbits
41309005
(1989)
Doses:
0,
50,
400,
or
1000
mg/
kg/
day
Acceptable
NOAEL
=
1000
mg/
kg/
day.
LOAEL
=
was
not
identified
for
systemic
and
dermal
toxicity.
870.3250
90
Day
dermal
toxicity
Not
required
870.3465
21
Day
inhalation
toxicity
in
the
rat
00063972
(1976)
Dose:
0,
2.5
mg/
L
Unacceptable/
upgradable
No
documentation
was
submitted
with
a
summary
of
an
inhalation
study.
870.3465
90
Day
inhalation
toxicity
The
90
day
inhalation
study
is
not
required,
however
a
28
Day
inhalation
study
is
required
(contact
Agency
prior
to
conducting
study)
870.3700a
Prenatal
developmental
in
rats
40397501
(1980)
Doses:
0,
40,
100,
400,
or
900
mg/
kg
Acceptable
Maternal
NOAEL
=
100
mg/
kg/
day
LOAEL
=
400
mg/
kg/
day
based
on
decreased
food
consumption
during
dosing
and
nominal
decreases
in
body
weight
gain
from
day
7
to
day
17
and
at
all
measured
intervals
between
and
at
900
mg/
kg/
day
on
mortality
and
decreased
body
weight
gains
and
food
consumption.
Developmental
NOAEL
=
400
mg/
kg/
day
LOAEL
=
900
mg/
kg/
day
based
on
decreased
female
fetal
weight,
and
increased
incidence
of
kidneys
with
no
papilla
(malformation),
and
an
increased
incidence
of
misaligned
sternebrae
(variation).
870.3700a
Prenatal
developmental
in
rats
00114486
(1974)
Doses:
0,
200,
1000,
or
5000
ppm
(equivalent
to
0,
18.9,
94.5,
and
482.0
mg/
kg)
Unacceptable/
Upgradable
Maternal:
NOAEL
is
1000
ppm
(equivalent
to
94.5
mg/
kg/
day).
LOAEL
=
5000
ppm
(equivalent
to
482
mg/
kg/
day)
based
on
decreased
body
weights,
body
weight
gains,
and
food
efficiency.
Developmental:
NOAEL
=
5000
ppm
(equivalent
to
482.0
mg/
kg/
day).
LOAEL
was
not
observed.
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
Page
33
of
38
870.3700b
Prenatal
developmental
in
rabbits
45677801
(2002)
Doses:
0,
50,
125,
175
mg/
kg/
day
Acceptable
Maternal:
NOAEL
=
50
mg/
kg/
day.
LOAEL
=
125
mg/
kg/
day
based
body
weight
and
food
consumption
decrement.
Developmental:
NOAEL
=
50
mg/
kg/
day.
LOAEL
=
125
mg/
kg/
day
based
on
5%
decrement
in
male
and
female
fetal
weight
and
a
10%
decrement
in
female
fetal
weight.
870.3700b
Prenatal
developmental
in
rabbits
00028863
(1980)
Doses:
0,
20,
50,
or
125
mg/
kg
Unacceptable/
Upgradable
Maternal
NOAEL
=
50
mg/
kg/
day
LOAEL
=
125
mg/
kg/
day
based
on
transient
decreases
in
food
consumption
and
body
weight
gains.
Developmental
NOAEL
=
50
mg/
kg/
day
LOAEL
=
125
mg/
kg/
day
based
on
possible
skeletal
abnormalities
and
total
abnormalies.
870.3800
Reproduction
and
fertility
effects
in
rats
42066501
(1991)
Doses:
0,
200,
2000
or
5000
ppm
M:
0,
11.8,
117
or
294
mg/
kg/
day
F:
0,
14.3,
143
or
383
mg/
kg/
day
Acceptable
Parental/
Systemic
NOAEL
=
14.3
mg/
kg/
day
LOAEL
=
143
mg/
kg/
day
based
on
male
body
weight
decrement.
Reproductive
NOAEL
=
383
mg/
kg/
day
LOAEL
=
None
based
on
no
effects
on
or
organs
of
reproduction.
Offspring
NOAEL
=
14.3
mg/
kg/
day
LOAEL
=
143
mg/
kg/
day
based
on
reduced
female
pup
weight
at
birth
and
during
lactation.
870.4100a
Chronic
toxicity
in
rats
See
870.4300
NOAEL
=
LOAEL
=
870.4100b
Chronic
toxicity
dogs
42162301
(1991)
Doses:
0,
200,
1500,
or
6000
ppm
(equivalent
to
5.00/
4.97,
41.24/
37.6
and
161/
167
mg/
kg/
day,
male/
female.
Acceptable
NOAEL
=
200
ppm
(5.0/
5.0
mg/
kg/
day,
male/
female)
LOAEL
=
1500
ppm
(41.2
and
37.57
mg/
kg/
day,
respectively)
based
on
thinness
in
one
male
and
hepatotoxicity
as
evidenced
by
changes
in
clinical
chemistry
parameters
and
microscopic
lesions.
870.4200
Carcinogenicity
rats
See
below
870.4300
No
evidence
of
carcinogenicity
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
Page
34
of
38
870.4200
Carcinogenicity
mice
00079203
(1981),
41359301
(1989),
42509301
(1992)
and
43202901
(1994)
Doses:
0,
0,
200,
2500
or
10,000
ppm
(equivalent
to
28/
34,
366/
450
and
1635/
1915
mg/
kg/
day,
male/
female)
Acceptable
NOAEL
=
200/
2500
ppm
(28/
450
mg/
kg/
day,
male/
female,
respectively)
LOAEL
=
2500
ppm
for
males
(equivalent
to
366
mg/
kg/
day)
based
on
gross
liver
nodules/
masses,
hyperplastic
nodules
in
the
liver
and
centrilobular
hepatocyte
hypertrophy
and
10,000
ppm
for
females
(equivalent
to
1915
mg/
kg/
day
[limit
dose])
based
on
decreased
body
weights,
increased
relative
liver/
gall
bladder
weights,
hyperplastic
nodules
and
centrilobular
hepatocyte
hypertrophy.
Insufficient
evidence
for
carcinogenicity.
870.4300
Combined
chronic/
carcinogenicity/
rats
00108638
(1977)
Doses:
0,
200,
1000,
or
2500
ppm
(equivalent
to
0,
10.2/
12.5,
53.4/
67.5,
or
138/
179
mg/
kg/
day,
male/
female)
Acceptable
NOAEL
=
200
ppm
for
males
and
females
(10.2/
12.5
mg/
kg/
day,
male/
female).
LOAEL
=
1000
ppm
for
males
and
females
(equivalent
to
53.3/
67.5
mg/
kg/
day,
male/
female)
based
on
decreased
body
weight
and
food
efficiency
in
males
and
females.
In
males
at
2500
ppm
the
body
weight
decrement
and
food
efficiency
decrement
occurred
only
for
the
first
6
months
of
the
study.
The
carcinogenic
potential
of
hexazinone
is
considered
negative.
Gene
mutation
870.5100;
Reverse
mutation
in
Salmonella
strains
40826201
(1977)
200,
400,
600,
800
and
1000
:g/
plate
S9
and
400,
800,
1200,
1600
and
2000
:g/
mL
+
S9
mix.
Unacceptable
No
mutagenic
potential
was
seen,
but
doses
insufficent
to
cause
cell
toxicity.
Gene
mutation
870.5300;
hamster
CHO
cells/
HPRT
assay
00076956
(1980)
Trial
1
were
2.0,
11.1,
13.1,
13.9
and
14.3
mM
S9
and
2.0,
7.9,
8.9,
9.3
and
9.9
mM
+S9.
Trial
2
were
2.0,
5.9,
11.1,
13.1
and
13.9
mM
S9
and
2.0,
7.9,
8.9,
9.3
and
9.9
mM
+
S9.
Acceptable
No
evidence
of
mutagenic
potential
at
cytotoxic
doses.
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
Page
35
of
38
Cytogenics
870.5375;
Chromosomal
aberrations
in
hamster
CHO
cells
00130709
(1982)
In
Trial
1,
1.58,
3.94,
15.85
and
19.82
mM
S9
and
0.32,
3.17,
7.93
and
15.85
mM
+
S9.
In
Trial
2,
1.58,
3.94,
7.93
and
15.85
S9
0.32,
3.17,
7.93
and
15.85
mM
+
S9
Acceptable
Positive
for
structural
chromosomal
aberrations
with
and
without
S9.
Other
Effects
870.5385,
In
vivo
Rat
bone
marrow
cytogenics
assay
00131355
(1982)
Rat
doses:
100,
300
or
1000
mg/
kg
Unacceptable
No
evidence
of
mutagenic
potential,
but
insufficient
animals
and
cells
were
tested.
Other
Effects
870.5395
Mouse
bone
marrow
micronucleus
test
45124401
(2000)
Mouse
doses:
1000,
2000
and
3000
mg/
kg
Acceptable
No
evidence
of
clastogenic
or
aneugenic
effect
in
bone
marrow
at
toxic
doses..
Other
Effects
870.5550,
UDS
in
rat
hepatocytes
00130708
(1983)
Trial
1:
1
x
10
5
,
1
x
10
4
,
1
x
10
3
,
1
x
10
2
,
0.1,
1.0,
10.0
and
30.0
mM
and
Trial
2:
1
x
10
5
,
1
x
10
4
,
1
x
10
3
,
1
x
10
2
,
0.1,
1.0,
5.0,
10.0
and
30.0
mM.
Acceptable
No
evidence
of
mutagenic
potential
at
precipitating
dose
levels.
870.6200a
Acute
neurotoxicity
screening
battery
Not
required
870.6200b
Subchronic
neurotoxicity
screening
battery
Not
required
870.6300
Developmental
neurotoxicity
Not
required
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
Page
36
of
38
870.7485
Metabolism
and
pharmacokinetics
in
the
rat
00140162
&
00109237
(1980
&1982)
Acceptable
No
parent
was
seen
in
urine
or
feces,
which
was
rapidly
absorbed
and
excreted.
Two
identified
metabolites
resulted
from
hydroxylation
of
the
cyclohexyl
ring
and
differed
only
by
the
metabolic
conversion
of
the
6
dimethyl
amine
to
a
secondary
methyl
amine.
No
sex,
or
doserelated
differences
in
the
formation
and
excretion
of
these
metabolites
were
found.
870.7600
Dermal
penetration
Not
required
Special
studies
None
submitted
9.2
Summary
of
Toxicological
Dose
and
Endpoints
for
HEXAZINONE
for
Use
in
Human
Risk
Assessment
Exposure
Scenario
Dose
(mg/
kg/
day)
UF
/MOE
Hazard
Based
Special
FQPA
Safety
Factor
Endpoint
for
Risk
Assessment
Dietary
Risk
Assessments
Acute
Dietary
females
13
50
years
of
age
NOAEL
=
400
UF
=
100
Acute
RfD
=
4.0
mg/
kg/
day
1x
Developmental
Toxicity
Rat
LOAEL
is
900
mg/
kg/
day
based
on
decreased
male
and
female
fetal
weight,
kidneys
with
no
papilla
(malformation)
and
misaligned
sternebrae
(variation)
Acute
Dietary
general
population
including
infants
and
children
An
appropriate
endpoint
attributable
to
a
single
dose
was
not
identified
in
the
oral
studies,
including
the
rat
and
rabbit
developmental
studies.
Chronic
Dietary
all
populations
NOAEL=
5.0
UF
=
100
Chronic
RfD
=
0.05
mg/
kg/
day
1x
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Exposure
Scenario
Dose
(mg/
kg/
day)
UF
/MOE
Hazard
Based
Special
FQPA
Safety
Factor
Endpoint
for
Risk
Assessment
Page
37
of
38
Incidental
Oral
Short
Term
(1
30
Days)
Residential
Only
There
are
no
residential
uses
at
the
present
time
and
therefore,
endpoints
were
not
selected.
Incidental
Oral
Intermediate
Term
(1
6
Months)
Residential
Only
There
are
no
residential
uses
at
the
present
time
and
therefore,
endpoints
were
not
selected.
Non
Dietary
Risk
Assessments
Dermal
Short
Term
(1
30
days)
No
hazard
was
identified,
therefore
quantification
of
risk
is
not
required.
No
systemic
toxicity
was
seen
at
the
limit
dose
following
repeat
dermal
application,
and
there
were
no
concerns
for
developmental
or
reproductive
toxicity.
Residential
Occupational
Dermal
Intermediate
Term
1
(1
6
Months)
Oral
NOAEL=
5.0
mg/
kg/
day
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Residential
MOE=
N/
A
N/
A
Occupational
MOE=
100
N/
A
Dermal
Long
Term
1
(1
6
Months)
Oral
NOAEL=
5.0
mg/
kg/
day
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Residential
MOE=
N/
A
N/
A
Occupational
MOE=
100
N/
A
Inhalation
Short
Term
2
(1
30
days)
Oral
NOAEL=
50
mg/
kg/
day
Developmental
Toxicity
Rabbit
LOAEL
=
125
mg/
kg/
day
based
on
decreases
in
maternal
food
consumption
and
dose
related
body
weight
decrement
and
fetal
weight
decrement.
Residential
MOE=
N/
A
N/
A
Occupational
MOE=
100
N/
A
HEXAZINONE/
107201/
August/
2002
TRED
Toxicology
Chapter
Exposure
Scenario
Dose
(mg/
kg/
day)
UF
/MOE
Hazard
Based
Special
FQPA
Safety
Factor
Endpoint
for
Risk
Assessment
Page
38
of
38
Inhalation
Intermediate
Term
(1
6
Months)
Oral
NOAEL=
5.0
mg/
kg/
day
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Residential
MOE
=
N/
A
N/
A
Occupational
MOE=
100
N/
A
Inhalation
Long
Term
(>
6
Months)
Oral
NOAEL=
5.0
mg/
kg/
day
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Residential
MOE=
N/
A
N/
A
Occupational
MOE=
100
N/
A
Cancer
Classification:
D
Not
Classifiable
as
to
human
carcinogenicity
1
Since
an
oral
NOAEL
was
selected
12.5%
dermal
absorption
factor
should
be
used
for
route
to
route
exposures.
2
Absorption
via
the
inhalation
route
is
assumed
to
be
equivalent
to
oral
absorption.
N/
A
=
Not
Applicable;
there
are
no
residential
uses.
| epa | 2024-06-07T20:31:42.941641 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0022/content.txt"
} |
EPA-HQ-OPP-2002-0188-0023 | Supporting & Related Material | "2002-09-16T04:00:00" | null | 1
TXR
NO.
0051033
DATE:
August
12,
2002
MEMORANDUM
SUBJECT:
HEXAZINONE
3
rd
Report
of
the
Hazard
Identification
Assessment
Review
Committee.
FROM:
David
G.
Anderson
Toxicologist.
Reregistration
Branch
2
Health
Effects
Division
(7509C)
THROUGH:
Jess
Rowland,
Co
Chair
and
Elizabeth
Doyle,
Co
Chair
Hazard
Identification
Assessment
Review
Committee
Health
Effects
Division
(7509C)
TO:
Carol
Christensen,
Risk
Assessor
Reregistration
Branch
2
Health
Effects
Division
(7509C)
PC
Code:
107201
On
Dec
4,
2001,
the
Health
Effects
Division
(HED)
Hazard
Identification
Assessment
Review
Committee
(HIARC)
reviewed
the
recommendations
of
the
toxicology
reviewer
for
HEXAZINONE
with
regard
to
the
acute
and
chronic
Reference
Doses
(RfDs)
and
the
toxicological
endpoint
selection
for
use
as
appropriate
in
occupational/
residential
exposure
risk
assessments.
The
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
HEXAZINONE
was
also
evaluated
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996.
On
April
02,
2002,
HIARC
assessed
the
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996
under
the
2002
OPP
10X
guidance
document.
At
this
meeting,
the
HIARC
applied
a
database
uncertainty
factor
to
account
for
the
lack
of
a
developmental
toxicity
study
in
rabbits.
On
July
30,
2002,
HIARC
reviewed
the
new
rabbit
developmental
toxicity
study
submitted
to
the
Agency
on
May
3,
2002.
The
conclusions
drawn
at
the
three
meetings
are
presented
in
this
report.
2
Committee
Members
in
Attendance
Members
present
were:
Bill
Burnam,
Jonathan
Chen,
Pamela
Hurley,
John
Liccione,
Elizabeth
Mendez,
Jess
Rowland,
Brenda
Tarplee.
Member(
s)
in
absentia:
Ayaad
Assaad,
David
Nixon,
Beth
Doyle,
Sue
Makris,
Steve
Knizer.
Data
evaluation
prepared
by:
David
G.
Anderson,
RRB2
Also
in
attendance
were:
Carol
Christensen,
Pauline
Wagner
Data
Evaluation/
Report
presentation
David
G.
Anderson
Toxicologist
Report
Concurrence
Brenda
Tarplee,
Senior
Scientist
Science
Information
Management
Branch
3
INTRODUCTION
On
December
4,
2001,
the
Health
Effects
Division
(HED)
Hazard
Identification
Assessment
Review
Committee
(HIARC)
reviewed
the
recommendations
of
the
toxicology
reviewer
for
HEXAZINONE
with
regard
to
the
acute
and
chronic
Reference
Doses
(RfDs)
and
the
toxicological
endpoint
selection
for
use
as
appropriate
in
occupational/
residential
exposure
risk
assessments.
The
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
HEXAZINONE
was
also
evaluated
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996.
On
April
02,
2002,
HIARC
assessed
the
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996
under
the
2002
OPP
10X
guidance
document.
At
this
meeting,
the
HIARC
applied
a
database
uncertainty
factor
to
account
for
the
lack
of
a
developmental
toxicity
study
in
rabbits.
On
July
30,
2002,
HIARC
reviewed
the
new
rabbit
developmental
toxicity
study
submitted
to
the
Agency
on
May
3,
2002.
The
conclusions
drawn
at
the
three
meetings
are
presented
in
this
report.
I
FQPA
HAZARD
CONSIDERATIONS
1.
Adequacy
of
the
Toxicity
Data
base
The
HIARC
considered
that
the
toxicology
database
for
hexazinone
is
complete,
except
for
a
needed
confirmatory
28
day
inhalation
study.
2.
Evidence
of
Neurotoxicity
The
HIARC
concluded
that
there
is
not
a
concern
for
neurotoxicity
resulting
from
exposure
to
hexazinone.
3.
Developmental
Toxicity
Study
Conclusions
3.1
Developmental
toxicity
in
rats
(1987)
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
40397501),
hexazinone
(99.26%
a.
i.;
Lot#
S30306A,
Batch#
2/
36)
in
0.5%
methylcellulose
was
administered
orally
via
gavage
to
25
Crl:
CD
®
BR
female
rats/
group
at
dose
levels
of
0,
40,
100,
400,
or
900
mg/
kg
on
gestation
day
(GD)
7
through
16.
The
dosing
volume
was
10
mL/
kg
(calculated
by
reviewers).
All
dams
were
sacrificed
on
GD
22
and
their
fetuses
removed
by
cesarean
and
examined.
When
compared
to
concurrent
controls,
no
treatment
related
changes
in
clinical
signs,
gross
pathology,
pregnancy
rate,
live
fetuses,
resorptions,
pre
or
post
implantation
loss,
corpora
lutea,
or
implantations
were
noted
at
any
dose
level
tested.
No
treatment
related
findings
were
noted
in
the
100,
or
40
mg/
kg
groups.
4
In
the
900
mg/
kg
dams,
one
treatment
related
death
occurred;
alopecia
and
an
enlarged
stomach
containing
fluid
and
food
were
noted
at
necropsy.
Decreased
(p<
0.05)
body
weight
gains
were
noted
during
GDs
15
17
(
37%)
and
17
22
(
17%).
In
addition,
body
weight
gains
were
decreased
(p<
0.05)
for
the
overall
(GDs
7
17)
treatment
interval
(
30%).
Gravid
uterine
weights
were
not
reported;
however,
adjusted
(for
gravid
uterine
weight)
terminal
body
weights
were
slightly
decreased
(
6%;
p
0.05).
A
significant
(p
0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
GDs
9
11,
15
17,
7
17,
and
17
22.
Decreased
(p
0.05)
food
consumption
was
observed
throughout
treatment
(GDs
7
17;
9
16
22%)
and
post
treatment
(GDs
17
22;
9
9%).
A
significant
(p
0.05)
trend
by
linear
combination
of
dose
ranks
from
analysis
of
variance
(ANOVA)
was
noted
for
GDs
7
9,
9
11,
11
13,
13
15,
15
17,
7
17,
and
17
22.
Also
a
significantly
decreased
food
consumption
was
seen
at
400
mg/
kg/
day
(GD9
11;
9
1%)
and
(GD
7
17;
9
8%).
In
addition,
relative
(to
body)
liver
weights
were
increased
(p
0.05)
in
the
400
(5.2%)
and
900
(5.6%)
mg/
kg
dams
compared
to
concurrent
controls
(4.9%).
Decreased
(p
0.05)
terminal
body
weights
were
noted
at
900
mg/
kg
(
6%).
A
significant
(p
0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
relative
liver
weights
and
adjusted
terminal
body
weights.
In
addition,
a
significant
(p
0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
absolute
liver
weights.
Despite
this
trend,
the
observed
increases
in
absolute
liver
weights
at
100,
400,
and
900
mg/
kg
(
1
8%)
were
not
statistically
significant.
Liver
weight
findings
are
considered
equivocal.
The
maternal
LOAEL
is
400
mg/
kg/
day
based
on
decreased
food
consumption
during
dosing
and
nominal
decreases
in
body
weight
gain
from
day
7
to
day
17
and
at
all
measured
intervals
between
and
at
900
mg/
kg/
day
on
mortality
and
decreased
body
weight
gains
and
food
consumption.
The
maternal
NOAEL
is
100
mg/
kg/
day.
In
the
900
mg/
kg/
day
group,
male
and
female
fetal
weights
were
decreased
(
21%;
p
0.05);
a
significant
(p
0.05)
trend
by
Jonckheere's
test
was
noted
for
this
parameter.
At
400
mg/
kg/
day,
the
female
fetal
weights
that
were
significantly
decreased
were
not
considered
to
be
biologically
significant.
At
necropsy,
an
increased
(p
0.05)
incidence
of
misaligned
sternebra
(1),
a
variation,
was
observed
(fetal
incidence:
0.0217;
litter
incidence:
0.30)
relative
to
concurrent
controls
(fetal
incidence:
0.0066;
litter
incidence:
0.09).
In
addition,
an
increased
(p
0.05)
incidence
of
misaligned
sternebrae
(2+),
a
variation,
was
noted
(fetal
incidence:
0.0217;
litter
incidence:
0.30)
relative
to
concurrent
controls
(fetal
incidence:
0.0033;
litter
incidence:
0.04).
Furthermore,
an
increased
incidence
of
kidneys
with
no
papilla
was
observed
(fetal
incidence:
0.0347;
litter
incidence:
0.25)
relative
to
concurrent
controls
(fetal
incidence:
0.0062;
litter
incidence:
0.04).
Although
the
incidence
was
not
statistically
significant,
a
dose
related
trend
(p
0.05)
was
observed.
The
developmental
toxicity
LOAEL
is
900
mg/
kg/
day,
based
on
decreased
male
and
female
fetal
weight,
increased
incidence
of
kidneys
with
no
papilla
(malformation),
and
an
increased
incidence
of
misaligned
sternebrae
(variation).
The
developmental
toxicity
NOAEL
is
400
mg/
kg/
day.
The
developmental
toxicity
study
in
the
rat
is
classified
acceptable/
guideline
(OPPTS
870.3700;
5
§83
3
a)
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
in
the
rat.
An
unacceptable
developmental
feeding
study
in
the
rat
shows
(MRID#
00114486)
a
maternal
body
weight
decrement
at
482
mg/
kg/
day
with
a
NOAEL
of
94.5
mg/
kg/
day
with
a
developmental
NOAEL
of
482mg/
kg/
day.
This
study
tends
to
add
support
the
acceptable
rat
developmental
(by
gavage)
toxicity
study.
3.2
Developmental
Toxicity
in
the
rabbit
(2002)
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
45677801)
[DXP
A3674]
hexazinone
(98.78
%
a.
i.,
batch/
lot#
DXP
A3694
329)
was
administered
to
22
female
[Hra:(
NZW)
SPF
strain]
rabbits/
group
by
gavage]
at
dose
levels
of
0,
20,
50,
125
or
175
mg/
kg
bw/
day
from
days
7
through
28
of
gestation.
Maternal
toxicity
was
demonstrated
by
statistically
significant
findings
at
125
mg/
kg/
day
of
a
body
weight
gain
decrement
of
102
g
between
gd
7
9
and
57
g
between
gd
9
11,
food
consumption
decrement
of
18%,
abortions,
death
and
clinical
signs
such
as
diarrhea,
stained
cageboard
and
tail.
Only
1
dam
and
1
litter
survived
to
termination
at
175
mg/
kg/
day.
The
maternal
LOAEL
is
125
mg/
kg
bw/
day,
based
on
body
weight
gain
decrement,
decreased
food
consumption,
abortions,
death
and
clinical
signs
including
abnormal
gait
at
175
mg/
kg/
day.
The
maternal
NOAEL
is
50
mg/
kg
bw/
day.
No
dose
related
external,
visceral
or
skeletal
findings
were
noted.
Since
only
1
dam
with
1
litter
survived
to
termination
at
the
175
mg/
kg/
day
dose,
evaluation
of
embryo/
fetal
effects
at
this
dose
are
meaningless.
Random
malformations
were
seen
in
control
and
the
highest
dose
group
with
no
dose
relationship.
Mean
male
and
female
fetal
weight
was
reduced
by
5%
and
female
fetal
weight
was
reduced
by
10%
at
125
mg/
kg/
day.
Although
this
weight
reduction
was
not
list
as
being
statistically
significant,
the
author
stated
that
this
slight
weight
reduction
at
125
mg/
kg/
day
was
a
developmental
effect
level
and
this
reviewer
agrees.
The
developmental
LOAEL
is
125
mg/
kg
bw/
day,
based
on
mean
male
and
female
fetal
weight
decrement
and
female
fetal
weight
decrement.
The
developmental
NOAEL
is
50
mg/
kg
bw/
day.
The
developmental
toxicity
study
in
the
rabbit
is
classified
acceptable
(guideline)
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
(OPPTS
870.3700;
OECD
414)
in
the
rabbit.
3.3
Developmental
Toxicity
in
the
rabbit
(1980)
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
00028863),
hexazinone
(100%
a.
i.;
Lot/
batch
#
E21216A)
was
administered
orally
via
gavage
in
a
dosing
volume
of
1
mL/
kg)
to
17
female
New
Zealand
White
rabbits/
group
at
dose
levels
of
0,
20,
50,
or
125
mg/
kg
on
GD
6
through
19.
All
does
(except
those
that
died
or
delivered
prematurely)
were
sacrificed
on
GD
29,
and
their
fetuses
removed
by
cesarean
and
examined.
When
compared
to
concurrent
controls,
no
treatment
related
changes
in
mortality,
clinical
signs,
body
weights,
gross
pathology,
fetal
weights,
sex
ratios,
pre
implantation
or
post
6
implantation
losses,
or
the
number
of
corpora
lutea,
implantations,
resorptions,
live
fetuses,
or
dead
fetuses
were
observed.
At
125
mg/
kg,
food
consumption
was
decreased
(p
0.05),
relative
to
concurrent
controls,
at
the
beginning
of
treatment
from
GD
7
through
11
(
61
89%).
Decreases
in
food
consumption,
that
were
not
statistically
significant,
continued
throughout
treatment
(GDs
12
19;
9
2
37%).
Diminished
food
consumption
resulted
in
decreased
(not
statistically
significant)
body
weight
gains
in
the
does
(
241.5
g)
relative
to
concurrent
controls
(
7.2
g)
during
GDs
6
11.
However,
weight
gain
in
these
animals
recovered
quickly
and
was
higher
than
control
animals
during
subsequent
treatment
intervals
(GDs
11
15
and
15
19).
The
maternal
LOAEL
is
125
mg/
kg/
day
based
on
transient
decreases
in
food
consumption
and
body
weight
gains.
The
maternal
NOAEL
is
50
mg/
kg/
day.
At
125
mg/
kg/
day,
the
following
skeletal
variations
were
noted
(data
presented
as
fetal
incidence
vs.
0
controls):
(i)
lagging
ossification
in
extremities
(0.0882);
(ii)
malaligned
thoracic
vertebrae
(0.0294);
and
(iii)
flexed
wrist(
s)
(0.0294).
In
addition,
non
ossified
thumb,
an
anomaly,
was
noted
at
an
increased
incidence
(0.0294)
relative
to
concurrent
controls
(0).
In
the
absence
of
historical
control
data,
these
findings
are
considered
treatment
related.
In
addition,
it
could
not
be
determined
how
many
of
these
nominally
increased
incidences
were
from
different
litters,
which
would
have
increased
concern
for
developmental
toxicity.
The
developmental
toxicity
LOAEL
is
125
mg/
kg/
day,
based
on
possible
skeletal
abnormalities
and
total
abnormalities.
The
developmental
toxicity
NOAEL
is
50
mg/
kg/
day.
The
developmental
toxicity
study
in
the
rabbit
is
classified
unacceptable/
upgradable,
pending
submission
of
acceptable
purity,
concentration,
stability
and
litter
data
and
historical
control
data.
A
letter
dated
9/
26/
01
from
the
registrant
provided
no
additional
information
about
this
rabbit
developmental
toxicity
study
other
than
that
the
doses
were
not
analyzed
and
that
a
repeat
rabbit
developmental
toxicity
was
currently
being
conducted.
4.
Reproductive
Toxicity
Study
Conclusions
(1991)
4.1
Executive
Summary:
In
a
two
generation
reproduction
study,
hexazinone
(98%
a.
i.,
Lot
No.
T02118994)
was
administered
to
groups
of
30
male
and
30
female
Sprague
Dawley
rats
in
the
diet
at
concentrations
of
0,
200,
2000,
or
5000
ppm
(MRID
42066501).
One
litter
was
produced
in
the
first
generation
and
two
litters
were
produced
in
the
second
generation.
Test
substance
intake
for
the
treated
F0
groups
was
11.8,
117,
and
294
mg/
kg/
day,
respectively,
for
males
and
14.3,
143,
and
383
mg/
kg/
day,
respectively,
for
females.
Test
substance
intake
for
the
treated
F1
groups
was
15.3,
154,
and
399
mg/
kg/
day,
respectively,
for
males
and
17.7,
180,
and
484
mg/
kg/
day,
respectively,
for
females.
F0
and
F1
parental
animals
were
administered
test
or
control
diet
for
73
or
105
days,
respectively,
prior
to
mating,
throughout
mating,
gestation,
and
lactation,
and
until
necropsy.
Deaths
of
several
F0
and
F1
parental
animals
were
considered
incidental
to
treatment.
No
treatment
related
clinical
signs
of
toxicity
were
observed
in
the
adult
animals
of
either
generation.
7
Gross
necropsy
was
unremarkable
and
no
microscopic
lesions
were
observed
in
selected
tissues
from
the
reproductive
tracts
of
male
and
female
parental
animals.
Body
weights
and
body
weight
gains
of
the
F0
males
were
not
affected
by
treatment.
Premating
body
weight
gains
by
the
mid
and
high
dose
F0
females
were
76%
and
62%
(p
#
0.05
for
both),
respectively,
of
the
control
level
resulting
in
final
premating
body
weights
93%
and
87%
(p
#
0.05),
respectively,
of
the
controls.
Body
weights
of
the
high
dose
F1
males
and
females
were
significantly
reduced
(p
#
0.05)
during
the
premating
interval
with
overall
weight
gains
87%
and
82%,
respectively,
of
the
control
group
amounts.
Reductions
in
body
weights
and
body
weight
gains
during
premating
for
the
mid
and
high
dose
F0
and
high
dose
F1
dams
continued
during
gestation
and
lactation.
Food
consumption
during
premating
was
similar
between
the
treated
and
control
groups
for
males
and
females
of
both
generations.
However,
during
gestation
significantly
(p
#
0.05)
lower
food
consumption
was
noted
for
the
high
dose
F1
dams
during
production
of
both
litters
and
for
the
mid
dose
F1
dams
during
production
of
the
second
litter.
There
was
a
statistically
significant
increase
in
absolute
P0
testes
weight
that
appeared
to
be
dose
related,
but
a
nominally
decrease
absolute
F1
adult
testes
weight
in
the
5000
ppm
dose
groups.
The
F1
testes
weight
change
did
not
appear
to
dose
related.
The
testes
weight
changes
in
males
would
appear
to
be
incidental.
Therefore,
the
systemic
toxicity
LOAEL
is
2000
ppm
(117
154
mg/
kg/
day
for
males
and
143
180
mg/
kg/
day
for
females)
based
on
reduced
body
weight
and
body
weight
gains
by
F1
males
and
F0
and
F1
females.
The
systemic
toxicity
NOAEL
is
200
ppm
(11.8
15.3
mg/
kg/
day
for
males
and
14.3
17.7
mg/
kg/
day
for
females).
No
reproductive
effects
were
seen
in
the
study
except
for
the
weight
effects
on
offspring.
Live
birth
and
viability
indices
and
litter
survival
were
similar
between
the
treated
and
control
groups.
The
lactation
index
for
the
F2b
high
dose
litters
was
85.8%
(p
#
0.05)
compared
to
97.5%
for
the
control
group.
Pup
body
weights
were
decreased
throughout
lactation
in
the
mid
and
high
dose
groups
of
all
litters
as
compared
with
the
control
groups
with
statistical
significance
(p
#
0.05)
attained
at
most
time
points.
The
lower
pup
body
weights
were
more
pronounced
in
females
than
in
males.
F1
and
F2a
female
pup
weights
were
statistically
significantly
decreased
at
birth,
day
7
and
14
of
lactation
at
$
2000
ppm.
There
were
no
obvious
reproductive
effects
other
than
the
pup
weight
decrement.
Therefore,
the
offspring
LOAEL
is
2000
ppm
(117
154
mg/
kg/
day
for
males
and
143
180
mg/
kg/
day
for
females)
based
on
reduced
female
pup
body
weights
at
birth
and
during
lactation.
The
reproductive
toxicity
NOAEL
was
200
ppm
(11.8
15.3
mg/
kg/
day
for
males
and
14.3
17.7
mg/
kg/
day
for
females).
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
guideline
requirements
for
a
reproductive
toxicity
study
[OPPTS
870.3800
(§
83
4)]
in
rats.
8
5.
Additional
Information
from
Literature
Sources
The
published
literature
found
on
hexazinone
were
the
papers
on
the
same
studies
submitted
to
the
Agency
[
Kennedy,
GL
and
Kaplan,
AM
(1984)
Chronic
Toxicity,
Reproductive,
and
Teratogenic
Studies
of
Hexazinone.
Fundamental
and
applied
Toxicology
4,
960
971].
6.
Pre
and
/or
Postnatal
Toxicity
The
HIARC
concluded
that
there
is
not
a
concern
for
pre
and
postnatal
toxicity
resulting
from
exposure
to
hexazinone.
A.
Determination
of
Susceptibility
No
quantitative
or
qualitative
evidence
of
increased
susceptibility
was
seen
following
in
utero
or
pre/
post
natal
exposure
to
rats
or
rabbits.
In
the
rat
developmental
toxicity
study,
developmental
effects
were
seen
at
a
higher
dose
than
the
dose
that
caused
maternal
toxicity.
In
the
rabbit
study,
fetal
weight
decrement
was
seen
at
the
same
dose
that
caused
maternal
weight
decrement.
In
the
two
generation
reproduction
study,
offspring
toxicity
was
seen
at
the
same
dose
that
caused
parental
toxicity.
B.
Degree
of
Concern
Analysis
and
Residual
Uncertainties
There
is
no
evidence
for
increased
susceptibility,
therefore,
no
residual
concerns
.
C.
Hazard
based
Special
FQPA
Safety
Factors
The
special
FQPA
Safety
Factor
can
be
reduced
to
1x
due
to
lack
of
evidence
for
increased
susceptibility
and
no
residual
concerns.
7.
Recommendation
for
a
Developmental
Neurotoxicity
Study
A.
Evidence
that
suggests
requiring
a
Developmental
neurotoxicity
study:
None
B.
Evidence
that
do
not
support
the
need
for
a
Developmental
Neurotoxicity
study
No
evidence
of
neurotoxicity
or
neuropathology
was
seen
in
the
database.
A
12
13%
absolute
female
brain
decrement
was
seen
in
the
chronic
dog
study,
but
the
brain
weight
decrement
was
associated
with
severe
body
weight
decrement
and
may
have
been
secondary
to
the
malnutrition
in
these
animals.
Hexazinone
differs
structurally
from
atrazine
such
that
it
is
unlikely
to
bind
to
the
same
receptor
and
not
likely
to
result
in
similar
effects.
Based
on
the
weight
of
evidence
presented,
the
HIARC
concluded
that
a
developmental
nuerotoxicity
study
is
not
required.
9
II.
HAZARD
IDENTIFICATION
1.
Acute
Reference
Dose
(RfD)(
Population
Subgroup:
Females
13
50)
Study
Selected:
Developmental
toxicity
Study
in
Rats
§
870.3700
MRID
No.:
40397501
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
40397501),
hexazinone
(99.26%
a.
i.;
Lot#
S30306A,
Batch#
2/
36)
in
0.5%
methylcellulose
was
administered
orally
via
gavage
to
25
Crl:
CD
®
BR
female
rats/
group
at
dose
levels
of
0,
40,
100,
400,
or
900
mg/
kg
on
gestation
day
(GD)
7
through
16.
The
dosing
volume
was
10
mL/
kg
(calculated
by
reviewers).
All
dams
were
sacrificed
on
GD
22
and
their
fetuses
removed
by
cesarean
and
examined.
When
compared
to
concurrent
controls,
no
treatment
related
changes
in
clinical
signs,
gross
pathology,
pregnancy
rate,
live
fetuses,
resorptions,
pre
or
post
implantation
loss,
corpora
lutea,
or
implantations
were
noted
at
any
dose
level
tested.
No
treatment
related
findings
were
noted
in
the
100,
or
40
mg/
kg
groups.
In
the
900
mg/
kg
dams,
one
treatment
related
death
occurred;
alopecia
and
an
enlarged
stomach
containing
fluid
and
food
were
noted
at
necropsy.
Decreased
(p<
0.05)
body
weight
gains
were
noted
during
GDs
15
17
(
37%)
and
17
22
(
17%).
In
addition,
body
weight
gains
were
decreased
(p<
0.05)
for
the
overall
(GDs
7
17)
treatment
interval
(
30%).
Gravid
uterine
weights
were
not
reported;
however,
adjusted
(for
gravid
uterine
weight)
terminal
body
weights
were
slightly
decreased
(
6%;
p
0.05).
A
significant
(p
0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
GDs
9
11,
15
17,
7
17,
and
17
22.
Decreased
(p
0.05)
food
consumption
was
observed
throughout
treatment
(GDs
7
17;
9
16
22%)
and
post
treatment
(GDs
17
22;
9
9%).
A
significant
(p
0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
GDs
7
9,
9
11,
11
13,
13
15,
15
17,
7
17,
and
17
22.
Also
a
significantly
decreased
food
consumption
was
seen
at
400
mg/
kg/
day
(GD9
11;
9
1%)
and
(GD
7
17;
9
8%).
In
addition,
relative
(to
body)
liver
weights
were
increased
(p
0.05)
in
the
400
(5.2%)
and
900
(5.6%)
mg/
kg
dams
compared
to
concurrent
controls
(4.9%).
Decreased
(p
0.05)
terminal
body
weights
were
noted
at
900
mg/
kg
(
6%).
A
significant
(p
0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
relative
liver
weights
and
adjusted
terminal
body
weights.
In
addition,
a
significant
(p
0.05)
trend
by
linear
combination
of
dose
ranks
from
ANOVA
was
noted
for
absolute
liver
weights.
Despite
this
trend,
the
observed
increases
in
absolute
liver
weights
at
100,
400,
and
900
mg/
kg
(
1
8%)
were
not
statistically
significant.
Liver
weight
findings
are
considered
equivocal.
The
maternal
LOAEL
is
400
mg/
kg/
day
based
on
decreased
food
consumption
during
dosing
and
nominal
decreases
in
body
weight
gain
from
day
7
to
day
17
and
at
all
measured
intervals
between
and
at
900
mg/
kg/
day
on
mortality
and
decreased
body
weight
gains
and
food
consumption.
The
maternal
NOAEL
is
100
mg/
kg/
day.
10
In
the
900
mg/
kg/
day
group,
male
and
female
fetal
weights
were
decreased
(
21%;
p
0.05);
a
significant
(p
0.05)
trend
by
Jonckheere's
test
was
noted
for
this
parameter.
At
400
mg/
kg/
day,
only
female
fetal
weights
were
significantly
decreased
(2%)
but
were
not
considered
to
biologically
significantly
depressed.
At
900
mg/
kg/
day,
an
increased
(p
0.05)
incidence
of
misaligned
sternebrae
(1),
a
variation,
was
observed
(fetal
incidence:
0.0217;
litter
incidence:
0.30)
relative
to
concurrent
controls
(fetal
incidence:
0.0066;
litter
incidence:
0.09).
In
addition,
an
increased
(p
0.05)
incidence
of
misaligned
sternebrae
(2+),
a
variation,
was
noted
(fetal
incidence:
0.0217;
litter
incidence:
0.30)
relative
to
concurrent
controls
(fetal
incidence:
0.0033;
litter
incidence:
0.04).
Furthermore,
an
increased
incidence
of
kidneys
with
no
papilla
was
observed
(fetal
incidence:
0.0347;
litter
incidence:
0.25)
relative
to
concurrent
controls
(fetal
incidence:
0.0062;
litter
incidence:
0.04).
Although
the
incidence
was
not
statistically
significant,
a
dose
related
trend
(p
0.05)
was
observed.
The
developmental
toxicity
LOAEL
is
900
mg/
kg/
day,
based
on
decreased
male
and
female
fetal
weight
and
increased
incidence
of
kidneys
with
no
papilla
(malformation),
and
an
increased
incidence
of
misaligned
sternebrae
(variation).
The
developmental
toxicity
NOAEL
is
400
mg/
kg/
day.
The
developmental
toxicity
study
in
the
rat
is
classified
acceptable/
guideline
(OPPTS
870.3700;
§83
3
a)
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
in
the
rat.
Dose
and
Endpoint
for
Establishing
RfD:
Developmental
NOAEL
is
400
mg/
kg/
day.
The
LOAEL
is
900
mg/
kg/
day
based
on
increased
kidneys
with
no
papillae
and
misaligned
sternebrae.
Uncertainty
Factor
(UF):
100
(10X
intraspecies
variation;
10X
interspecies
extrapolation)
Comments
about
Study/
Endpoint/
Uncertainty
Factor:
The
malformations
(kidneys
with
no
papillae)
are
presumed
to
occur
after
a
single
and
thus
appropriate
for
this
risk
assessment.
In
the
rabbit
developmental
study
(MRID#
45677801)
abortions
occurred
later
in
gestation
(GD
18
27)
and
therefore
was
not
considered
to
be
appropriate
for
this
exposure
scenario.
Also,
the
one
death
in
the
maternal
animal
at
125
mg/
kg/
day
that
occurred
on
gestation
day
8
was
discounted
due
to
a
lack
of
dose
response
and
one
death
in
control
rabbits.
At
175
mg/
kg/
day,
maternal
death
occurred
late
in
gestation.
2.
Acute
Reference
Dose
(RfD)(
General
Population)
An
appropriate
endpoint
attributable
to
a
single
dose
was
not
identified
in
the
oral
studies,
including
the
rat
and
rabbit
developmental
studies.
Acute
RfD
(Females
13
50)
=
400
mg/
kg
(NOAEL)
=
4.0
mg/
kg
100
(UF)
11
3.
Chronic
Reference
Dose
(RfD)
Study
Selected:
One
Year
Chronic
Dog
Study
Guideline
#:
870.4100
MRID
No.:
42162301
Executive
Summary:
In
a
one
year
chronic
toxicity
study,
hexazinone
(98%
a.
i.,
Lot
No.
T02118994)
was
administered
to
groups
of
5
male
and
5
female
beagle
dogs
in
the
diet
at
concentrations
of
0,
200,
1500,
or
6000
ppm
(MRID
42162301).
Time
weighted
average
doses
for
the
treated
groups
were
5.00,
41.24,
and
161.48
mg/
kg/
day,
respectively,
for
males
and
4.97,
37.57,
and
166.99
mg/
kg/
day,
respectively,
for
females.
All
animals
survived
to
scheduled
necropsy.
Treatment
related
clinical
signs
of
toxicity
included
the
observation
of
thinness
in
1/
5
mid
dose
males,
3/
5
high
dose
males,
and
1/
5
high
dose
females.
Body
weights
of
the
high
dose
groups
were
significantly
(p
#
0.05)
less
than
those
of
the
control
throughout
most
of
the
study.
Final
body
weights
of
the
high
dose
males
and
females
were
78%
and
67%,
respectively,
of
the
control
levels.
Food
consumption
by
the
high
dose
groups
was
slightly
(n.
s.)
less
than
that
of
the
controls
throughout
the
study
with
statistical
significance
(p
#
0.05)
attained
for
females
at
week
52.
Overall
food
consumption
(weeks
1
52)
for
high
dose
males
and
females
was
85%
(n.
s.)
and
74%
(p
#
0.05),
respectively,
of
the
control
group
levels.
Body
weights
and
food
consumption
for
the
low
and
mid
dose
groups
were
not
affected
by
treatment.
No
treatment
related
ophthalmological
lesions,
changes
in
urinalysis
parameters,
or
gross
necropsy
findings
were
noted.
A
moderate
macrocytic
anemia
was
observed
in
the
high
dose
groups
as
evidenced
by
slight
or
significant
(p
#
0.05)
decreases
in
RBC
counts,
hemoglobin,
and
hematocrit
and
increases
in
MCV
and
MCH
in
one
or
both
sexes
throughout
the
study.
Cholesterol
levels
were
significantly
(p
#
0.05)
decreased
in
the
high
dose
groups
beginning
at
week
13
for
males
(52
64%
of
controls)
and
at
week
26
for
females
(45
51%
of
controls).
Albumin
levels
were
significantly
(p
#
0.05)
decreased
in
the
mid
dose
males
(93%
of
controls)
at
week
13
only,
and
in
the
high
dose
males
(74
78%
of
controls)
and
females
(75
82%
of
controls)
throughout
the
study.
Beginning
on
week
13
or
26,
the
high
dose
groups
had
aspartate
aminotransferase
levels
140
203%
(p
#
0.05)
of
the
control
values
and
alanine
aminotransferase
levels
206
276%
(p
#
0.05)
of
the
control
values.
Alkaline
phosphatase
levels
were
significantly
(p
#
0.05)
increased
in
the
mid
dose
males
(259
409%
of
controls)
and
females
(163
194%
of
controls;
n.
s.)
beginning
at
week
26
and
in
the
high
dose
males
(346
1363%
of
controls)
and
females
(307
559%
of
controls)
beginning
at
week
13.
For
the
high
dose
animals,
decreases
in
absolute
testes
weights
in
males
and
kidney,
heart,
and
brain
weights
in
females
(
12%)
and
increases
in
relative
liver
weights
in
males
and
females
were
considered
due
to
lower
final
body
weights
of
these
animals
as
compared
with
controls.
Microscopic
lesions
in
the
liver
of
high
dose
animals
included
concentric
membranous
bodies
in
4
males
and
5
females,
centrilobular
single
cell
necrosis
in
3
males
and
3
females,
hepatocellular
pigment
in
3
males
and
3
females,
and
vacuolation
in
3
males
and
4
females.
In
addition
12
vacuolation
was
observed
in
one
mid
dose
male
and
pigment
and
membranous
bodies
were
each
observed
in
one
mid
dose
female.
These
lesions
were
not
seen
in
control
or
low
dose
animals.
Therefore,
the
LOAEL
for
hexazinone
in
male
and
female
beagle
dogs
is
1500
ppm
(41.24
and
37.57
mg/
kg/
day,
respectively)
based
on
thinness
in
one
male
and
hepatotoxicity
as
evidenced
by
changes
in
clinical
chemistry
parameters
and
microscopic
lesions.
The
NOAEL
is
200
ppm
(5.00
and
4.97
mg/
kg/
day,
respectively).
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
guideline
requirements
for
a
chronic
toxicity
study
[OPPTS
870.4100
(§
83
1b)]
in
dogs.
Dose
and
Endpoint
for
Establishing
RfD:
NOAEL
of
5.0
mg/
kg/
day
based
body
weight
decrement,
elevated
clinical
chemistry
values
(serum
alkaline
phosphatase,
serum
aspartate
aminotransferase),
other
changes
in
clinical
chemistry
values,
and
histopathologic
lesions
of
the
liver
at
38
mg/
kg/
day
(LOAEL).
Uncertainty
Factor(
s):
100
(10X
intraspecies
variation;
10X
interspecies
extrapolation)
Comments
about
Study/
Endpoint/
Uncertainty
Factor(
s):
Dose
and
endpoint
identified
following
long
term
exposure
in
the
most
sensitive
species.
4.
Incidental
Oral
Exposure:
Short
Term
(1
30
days)
and
Intermediate
Term
(1
Month
6
Months)
Toxicity
endpoints
for
incidental
oral
exposure
were
not
selected
since
there
are
no
residential
exposure
expected
or
anticipated
based
on
the
current
use
pattern.
5.
Dermal
Absorption
No
dermal
absorption
study
is
available.
For
dermal
absorption,
the
NOAEL
from
the
21
day
dermal
toxicity
study
at
the
limit
dose
of
1000
mg/
kg/
day
was
considered
a
lower
bound
for
the
LOAEL,
which
was
compared
with
LOAEL
of
125
mg/
kg/
day
from
the
new
developmental
toxicity
study
in
rabbits
(MRID#
45677801).
The
ratio
of
these
two
numbers
was
used
to
estimate
a
dermal
absorption
factor
of
12.5%.
Dermal
Absorption
Factor:
12.5%
Chronic
RfD
=
5.0
mg/
kg/
day
(NOAEL)
=
0.05
mg/
kg/
day
100
(UF)
13
6.
Short
Term
Dermal
(1
Day
1
Month)
Exposure
Study
Selected:
None
MRID
No.:
None
Executive
Summary:
None
Dose
and
Endpoint
for
Risk
Assessment:
Not
applicable
Comments
about
Study/
Endpoint:
Quantification
of
dermal
risk
is
not
required
since
no
hazard
was
identified
via
the
dermal
route
(no
systemic
toxicity
was
seen
at
the
Limit
Dose
(1000
mg/
kg/
day)
in
the
21
day
dermal
study
in
rabbits)
and
there
are
no
concerns
for
pre/
post
natal
toxicity
.
7.
Intermediate
Term
Dermal
(1
6
Months)
Study
Selected:
Chronic
Feeding
Study
in
Dogs
§
870.4100
MRID
No.:
42162301
Executive
Summary:
[See
Section
II.
3.
on
the
Chronic
Reference
Dose
(RfD).]
Dose/
Endpoint
for
Risk
Assessment:
NOAEL
of
5.0
mg/
kg/
day
is
based
on
elevated
clinical
chemistry
values
(serum
alkaline
phosphatase,
serum
aspartate
aminotransferase),
other
changes
in
clinical
chemistry
values,
liver
microscopic
findings
and
body
weight
decrement
and
the
clinical
observation
of
thinnest
in
one
males
at
38
mg/
kg/
day.
Comments
about
Study/
Endpoint:
The
elevation
in
clinical
chemistry
parameters
were
seen
at
3
and
6
months
and
thus
appropriate
for
the
exposure
period.
Since
an
oral
NOAEL
was
selected,
a
12.5%
dermal
absorption
factor
should
be
used
for
route
to
route
extrapolation.
8.
Long
Term
Dermal
(longer
than
6
Months)
Exposure
Study
Selected:
Chronic
Feeding
Study
in
Dogs
§
870.4100
MRID
No.:
42162301
Executive
Summary:
[See
Section
II.
3.
on
the
Chronic
Reference
Dose
(RfD).]
Dose/
Endpoint
for
Risk
Assessment:
NOAEL
of
5.0
mg/
kg/
day
is
based
on
elevated
clinical
chemistry
values
(serum
alkaline
phosphatase,
serum
aspartate
aminotransferase),
other
changes
in
clinical
chemistry
values,
liver
microscopic
findings
and
body
weight
decrement
and
the
clinical
observation
of
thinnest
in
one
males
at
38
mg/
kg/
day.
Comments
about
Study/
Endpoint:
The
elevation
in
clinical
chemistry
parameters
were
seen
at
3
,
14
6
and
12
months
and
thus
appropriate
for
the
exposure
period.
Since
an
oral
NOAEL
was
selected,
a
12.5%
dermal
absorption
factor
should
be
used
for
route
to
route
extrapolation.
9.
Short
Term
Inhalation
Exposure
(1
day
to
1
Month)
Study
Selected:
Developmental
Toxicity
in
the
Rabbit
§
870.3700
MRID
No.:
45677801
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
45677801)
[DXP
A3674]
hexazinone
(98.78
%
a.
i.,
batch/
lot#
DXP
A3694
329)
was
administered
to
22
female
[Hra:(
NZW)
SPF
strain]
rabbits/
group
by
gavage]
at
dose
levels
of
0,
20,
50,
125
or
175
mg/
kg
bw/
day
from
days
7
through
28
of
gestation.
Maternal
toxicity
was
demonstrated
by
statistically
significant
findings
at
125
mg/
kg/
day
of
a
body
weight
gain
decrement
of
102
g
between
gd
7
9
and
57
g
between
gd
9
11,
food
consumption
decrement
of
18%,
abortions,
death
and
clinical
signs
such
as
diarrhea,
stained
cageboard
and
tail.
Only
1
dam
and
1
litter
survived
to
termination
at
175
mg/
kg/
day.
The
maternal
LOAEL
is
125
mg/
kg
bw/
day,
based
on
body
weight
gain
decrement,
decreased
food
consumption,
abortions,
death
and
clinical
signs
including
abnormal
gait
at
175
mg/
kg/
day.
The
maternal
NOAEL
is
50
mg/
kg
bw/
day.
No
dose
related
external,
visceral
or
skeletal
findings
were
noted.
Since
only
1
dam
with
1
litter
survived
to
termination
at
the
175
mg/
kg/
day
dose,
evaluation
of
embryo/
fetal
effects
at
this
dose
are
meaningless.
Random
malformations
were
seen
in
control
and
the
highest
dose
group
with
no
dose
relationship.
Mean
male
and
female
fetal
weight
was
reduced
by
5%
and
female
fetal
weight
was
reduced
by
10%
at
125
mg/
kg/
day.
Although
this
weight
reduction
was
not
listed
as
being
statistically
significant,
the
author
stated
that
this
slight
weight
reduction
at
125
mg/
kg/
day
was
a
developmental
effect
level
and
this
reviewer
agrees.
The
developmental
LOAEL
is
125
mg/
kg
bw/
day,
based
on
mean
male
and
female
fetal
weight
decrement
and
female
fetal
weight
decrement.
The
developmental
NOAEL
is
50
mg/
kg
bw/
day.
The
developmental
toxicity
study
in
the
rabbit
is
classified
acceptable
(guideline)
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
(OPPTS
870.3700;
OECD
414)
in
the
rabbit.
Dose/
Endpoint
for
Risk
Assessment:
The
maternal
NOAEL
of
50
mg/
kg/
day
based
on
based
on
maternal
body
weight
and
food
consumption
decrement
and
fetal
weight
decrement
at
125
mg/
kg/
day
(LOAEL).
Comments
about
Study/
Endpoint:
In
the
absence
of
a
inhalation
study
an
oral
NOAEL
was
selected.
Absorption
via
the
inhalation
route
is
assumed
to
be
equivalent
to
oral
absorption.
15
9.
Intermediate
Term
inhalation
(1
Month
to
6
Months)
Exposure.
Study
Selected:
Chronic
Feeding
Study
in
Dogs
§
870.4100
MRID
No.:
42162301
Executive
Summary:
[See
Section
II
3.
on
the
Chronic
Reference
Dose
(RfD).]
Dose/
Endpoint
for
Risk
Assessment:
NOAEL
of
5.0
mg/
kg/
day
based
on
elevated
clinical
chemistry
values
(serum
alkaline
phosphatase,
serum
aspartate
aminotransferase),
other
changes
in
clinical
chemistry
values,
liver
microscopic
findings
and
body
weight
decrement
and
clinical
observation
of
thinnest
in
one
males
at
38
mg/
kg/
day.
Comments
about
Study/
Endpoint:
The
affects
seen
in
clinical
chemistry
values
at
3,
6
and
12
months
are
appropriate
for
these
exposure
periods.
Absorption
via
the
inhalation
route
is
presumed
to
be
equivalent
to
oral
absorption.
10.
Long
Term
Inhalation
(longer
than
6
Months)
Exposure.
Study
Selected:
Chronic
Feeding
Study
in
Dogs
§
870.4100
MRID
No.:
42162301
Executive
Summary:
[See
Section
II
3.
on
the
Chronic
Reference
Dose
(RfD).]
Dose/
Endpoint
for
Risk
Assessment:
NOAEL
of
5.0
mg/
kg/
day
based
on
elevated
clinical
chemistry
values
(serum
alkaline
phosphatase,
serum
aspartate
aminotransferase),
other
changes
in
clinical
chemistry
values,
liver
microscopic
findings
and
body
weight
decrement
and
clinical
observation
of
thinnest
in
one
males
at
38
mg/
kg/
day.
Comments
about
Study/
Endpoint:
The
affects
seen
in
clinical
chemistry
values
at
3,
6
and
12
months
are
appropriate
for
these
exposure
periods.
Absorption
via
the
inhalation
route
is
presumed
to
be
equivalent
to
oral
absorption.
11.
Margins
of
Exposure
for
Occupational/
Residential
Risk
Assessment
A
margin
of
exposure
of
100
is
adequate
for
occupational
dermal
and
inhalation
exposure.
There
is
no
non
occupational
(residential)
exposures
identified
at
this
time.
16
12.
Recommendation
for
Aggregate
Exposure
Risk
Assessments
Aggregate
exposure
risk
assessment
is
not
required
since
there
are
no
non
occupational
(residential)
uses
at
the
present
time.
III.
CLASSIFICATION
OF
CARCINOGENIC
POTENTIAL
1.
Combined
Chronic
Toxicity/
Carcinogenicity
Study
in
Rats
MRID
No.:
00108638
Executive
Summary:
In
this
combined
chronic/
oncogenicity
study
(MRID
00108638),
hexazinone
(94
96%
a.
i.;
Lot/
Batch
#:
6897
40
and
74.25)
was
administered
in
the
diet
to
ChR
CD
rats
(36/
sex/
group)
for
up
to
25
months
at
nominal
doses
of
0,
0,
200,
1000,
or
2500
ppm
(equivalent
to
0,
0,
10.2,
53.4,
and
138.3
mg/
kg/
day
in
males
and
0,
0,
12.5,
67.5,
and
178.6
mg/
kg/
day
in
females).
No
treatment
related
differences
were
observed
in
mortality,
clinical
signs,
food
consumption,
hematology,
clinical
chemistry,
organ
weights,
and
gross
or
microscopic
pathology.
No
adverse
effects
were
observed
in
the
200
ppm
animals.
There
were
several
signs
of
general
toxicity,
but
a
target
organ
could
not
be
clearly
identified
at
any
dose.
Terminal
body
weights
were
decreased
8%
in1000
ppm
and
20%,
p
0.05,
in
the
2500
ppm
females.
A
decrease
in
overall
body
weight
gain
(Days
0
728;
calculated
by
the
reviewers)
was
also
observed
in
the
1000
(
10%)
and
2500
ppm
(
25%)
females.
Nominal
decreases
in
body
weight
and
body
weight
gain
(
3
to
5%)
occurred
in
males
at
1000
ppm
during
the
study,
which
may
have
been
biologically
significant
at
the
end
of
the
study
(
12%
body
weight
and
14%
for
body
weight
gain).
Decreases
(p
values
not
calculated)
in
total
food
efficiency
were
observed
in
females
at
1000
10
and
2500
ppm
(
25%)
and
in
males
at
1000
ppm
during
the
study
with
overall
decrement
in
food
efficiency
in
1000
ppm
males
(
10%).
In
males
at
2500
ppm,
food
efficiency
was
depressed
for
the
first
6
months
of
the
study
(
25%),
but
from
6
months
to
the
end
of
the
study,
it
was
increased
139%.
The
reviewer
noted
problems
interpreting
the
body
weights
and
food
efficiency
in
males
at
the
top
dose
level,
which
were
not
consistent
with
the
mid
dose
level.
For
the
first
6
months
of
the
study
in
males,
a
body
weight
decrement
due
to
probable
toxicity
was
seen
at
1000
and
2500
ppm.
After
6
months
food
efficiency
in
males
at
the
1000
ppm
remained
less
than
controls
(
56%)
while
food
efficiency
at
2500
ppm
in
males
was
higher
than
controls
(+
139%)(
Table
4).
By
the
end
of
the
study,
male
body
weight
at
1000
ppm
was
12%
and
body
weight
gain
14%,
where
as
body
weight
and
body
weight
gain
in
males
at
2500
ppm
was
+3%
for
both
weight
and
gain.
The
reason
for
this
recovery
in
male
body
weight
decrement
at
2500
ppm
is
unknown,
but
it
appears
to
be
real.
[Since
absolute
and
relative
liver
weights
were
decreased
in
males
at
2500
ppm,
liver
enzyme
induction
allowing
the
recovery
seems
unproven.]
The
body
weight
decrement
at
1000
and
2500
ppm
with
recovery
in
body
weight
at
2500
ppm
indicates
the
an
adequate
dose
level
to
test
for
carcinogenicity
in
males
was
approached,
but
probably
not
attained.
Other
treatment
groups
were
similar
to
the
average
of
concurrent
controls.
17
Dosing
was
considered
adequate
based
on
decreased
body
weights,
body
weight
gains,
and
food
efficiency
in
the
2500
and
1000
ppm
females
and
food
efficiency
and
body
weights
in
the
2500
ppm
males
for
the
first
6
months.
Body
weight
(
12%)
and
body
weight
gain
(
14%)
in
males
at
1000
ppm
were
decreased
at
the
end
of
the
study,
in
addition
overall
food
efficiency
(
14%)
was
decreased
by
the
end
of
the
study.
Thus
female
body
weight
and
body
weight
gain
was
decreased
sufficiently
to
adequately
test
for
carcinogenicity.
Male
body
weight
and
body
weight
gain
at1000
ppm
appeared
to
be
adequate
to
test
for
carcinogenicity
by
the
end
of
the
study,
but
the
lack
of
dose
response
in
male
body
weight
and
body
weight
gain
at
2500
ppm
(showing
recovery
after
6
months
such
that
body
weight
and
body
weight
gain
were
higher
than
control
values)
may
indicate
problems
with
the
interpretation
of
the
body
weights
and
body
weight
gains
at
1000
ppm.
In
the
2500
ppm
males,
creatinine
was
increased
(NS)
in
the
urine
at
months
18
and
24
and
bilirubin
was
detected
at
month
18
and
24.
The
Sponsor
reported
that
the
urine
was
more
alkaline
in
the
2500
ppm
treatment
groups
(data
not
reported).
Also
at
2500
ppm,
decreased
(p
0.05)
absolute
and
relative
liver
and
kidney
organ
weights
were
observed
in
the
males
and
increased
(p
0.05)
relative
(to
body)
stomach
and
kidney
organ
weights
were
observed
in
the
females.
However,
histopathological
data
did
not
corroborate
these
findings.
The
LOAEL
is
1000
ppm
for
males
and
females
(equivalent
to
53.3
for
males
and
67.5
mg/
kg/
day
for
females)
based
on
decreased
body
weight
and
food
efficiency
in
males
and
females.
In
males
at
2500
ppm
the
body
weight
decrement
and
food
efficiency
decrement
occurred
only
for
the
first
6
months
of
the
study.
The
NOAEL
is
200
ppm
for
males
and
females
(10.2
for
males
and
12.5
mg/
kg/
day
for
females).
Neoplasm
data
were
evaluated
by
two
pathologists.
An
increase
incidence
of
thyroid
C
cell
adenomas
was
observed
in
the
2500
ppm
males,
but
when
analyzed
by
the
Fisher's
exact
test
(p>
0.10)
or
life
table
methods
(p>
0.20)
no
significant
differences
were
observed
between
controls
and
treated
groups.
Using
life
table
analyses
a
significant
(p<
0.05)
dose
response
trend
was
observed
in
thyroid
C
cell
tumors
in
only
one
of
the
two
pathology
reports.
Female
rats
did
not
show
any
potential
for
C
cell
thyroid
adenomas.
The
incidence,
malignancy
and
latency
of
tumors
were
comparable
among
control
and
treated
rats
of
both
sexes.
Under
the
conditions
of
this
study,
carcinogenic
potential
of
hexazinone
is
considered
negative.
The
submitted
study
is
classified
as
acceptable
for
guideline
870.4300
combined
chronic/
carcinogenicity
study
in
rats.
Discussion
of
Tumor
Data:
Neoplasm
data
were
evaluated
by
two
pathologists.
An
increase
incidence
of
thyroid
C
cell
adenomas
was
observed
in
the
2500
ppm
males,
but
when
analyzed
by
the
Fisher's
exact
test
(p>
0.10)
or
life
table
methods
(p>
0.20)
no
significant
differences
were
observed
between
controls
and
treated
groups.
Using
life
table
analyses
a
significant
(p<
0.05)
dose
response
trend
was
observed
in
thyroid
C
cell
tumors
in
only
one
of
the
two
pathology
reports.
Female
rats
did
not
show
any
potential
for
C
cell
thyroid
adenomas.
The
incidence,
malignancy
and
latency
of
tumors
were
comparable
among
control
and
treated
rats
of
both
sexes.
18
The
study
in
rats
does
not
support
a
carcinogenic
potential
for
hexazinone.
Adequacy
of
the
Dose
Levels
Tested:
The
dose
levels
in
female
rats
was
adequate
to
test
for
the
carcinogenic
potential
hexazinone.
There
was
an
adequate
body
weight
decrement
and
body
weight
gain
decrement
at
the
two
top
dose
levels.
The
dose
levels
in
male
rats
approached
an
adequate
dose
level
to
test
for
carcinogenic
potential
of
hexazinone.
There
may
have
been
an
adequate
body
weight
and
body
weight
gain
at
the
mid
dose
level
at
the
end
of
the
study
to
test
for
carcinogenic
potential
of
hexazinone,
however
body
weights
of
males
at
the
top
dose
level
behaved
atypically.
At
the
top
dose
level,
males
showed
a
adequate
body
weight
decrement
only
for
the
first
6
months
of
the
study
and
by
the
end
of
the
study,
body
weights
were
higher
than
the
average
of
the
two
controls.
The
reason
for
this
reversible
body
weight
decrement
is
unknown,
but
the
top
dose
level
in
males
was
one
half
the
top
dose
level
of
5000
ppm
in
the
90
day
subchronic
study
in
males
where
liver
toxicity
was
seen.
These
body
weight
decrements
in
males
and
females
are
supported
by
a
corresponding
decrements
in
food
efficiency.
2.
Carcinogenicity
Study
in
Mice
MRID
No.
41359301,42509301
and
4320290
§
870.4200
Executive
Summary:
In
this
mouse
oncogenicity
study
(MRIDs
00079203,
41359301,
42509301
and
43202901),
hexazinone
(
95%
a.
i.;
Lot/
Batch
#:
H
11,
265
and
265
2)
was
administered
in
the
diet
to
CD
1
mice
(80/
sex/
group)
for
up
to
104
weeks
at
nominal
doses
of
0,
200,
2500
or
10,000
ppm
(equivalent
to
28,
366
and
1635
mg/
kg/
day
in
males
and
0,
34,
450
and
1915
mg/
kg/
day
in
females).
No
treatment
related
differences
were
observed
in
mortality,
food
consumption,
food
efficiency
or
hematology.
Hepatotoxicity
was
evident
at
the
terminal
sacrifice.
Macroscopic
liver
nodule/
mass
(%
treated
vs
%
controls;
n
=
28
55)
was
observed
in
males
at
2500
(39%
vs
7%)
and
10,000
ppm
(33%).
Increased
incidences
(%
treated
vs
0%
controls;
n
=
38
55)
in
the
following
microscopic
liver
lesions
were
observed:
hyperplastic
nodule(
s)
(includes
both
foci
of
cellular
alteration
and
adenoma)
in
males
at
2500
(39%
vs
20%)
and
10,000
ppm
(36%)
and
in
females
at
10,000
ppm
(15%
vs
3%);
and
necrosis
(severity
and
type
unspecified)
in
the
10,000
ppm
males
(36%
vs
7%).
Centrilobular
hepatocyte
hypertrophy
was
observed
(%
treated
vs
%
controls)
at
the
terminal
sacrifice
(n
=
38
55)
in
males
at
2500
(18%
vs
0%)
and
10,000
ppm
(98%)
and
in
females
at
10,000
ppm
(46%
vs
0%)
and
in
the
dead
and
moribund
males
(n
=
25
40)
at
2500
(44%
vs
0%)
and
10,000
ppm
(60%).
Increased
(p
0.05
or
0.01)
liver/
gall
bladder
weights
were
observed
at
10,000
ppm
in
males
in
both
absolute
and
relative
to
body
weights
and
in
females
in
relative
to
body
weight.
Other
signs
of
toxicity
were
evident.
Distal
tail
tip
sloughing
and/
or
discoloration
was
observed
at
10,000
ppm
in
males
at
Weeks
13
104
and
in
females
at
Weeks
5
and
13
104.
Macroscopically,
tip
of
tail
missing/
sloughed
was
observed
at
the
terminal
sacrifice
in
the
10,000
ppm
males
(31%
vs
5%)
and
females
(61%
vs
11%)
and
in
the
dead
and
moribund
10,000
ppm
females
(46%
vs
2%).
The
toxicological
significance
of
these
findings
was
unclear.
Minor
decreases
(p
0.05
or
0.01)
in
body
weights
were
observed
in
the
10,000
ppm
treatment
groups
at
19
Weeks
13
104
in
both
sexes.
Overall
body
weight
gains
(calculated
by
the
reviewers)
were
decreased
in
the
10,000
ppm
males
(
25%)
and
females
(
31%).
The
LOAEL
is
2500
ppm
for
males
(equivalent
to
366
mg/
kg/
day)
based
on
gross
liver
nodules/
masses,
hyperplastic
nodules
in
the
liver
and
centrilobular
hepatocyte
hypertrophy
and
10,000
ppm
for
females
(equivalent
to
1915
mg/
kg/
day
[limit
dose])
based
on
decreased
body
weights,
increased
relative
liver/
gall
bladder
weights,
hyperplastic
nodules
and
centrilobular
hepatocyte
hypertrophy.
The
NOAEL
is
200
ppm
(equivalent
to
28
mg/
kg/
day)
for
males
and
2500
ppm
(equivalent
to
450
mg/
kg/
day)
for
females.
Liver
samples
were
first
evaluated
using
the
term
hyperplastic
nodule
which
did
not
clearly
distinguish
neoplasia
from
non
neoplasia.
Reevaluation
was
conducted
to
make
this
distinction,
and
no
significant
differences
were
observed
between
the
treatment
groups
and
the
concurrent
controls.
However
positive
trends
(p<
0.05)
were
observed
(%
treated
vs
%
controls)
in
focus/
foci
of
cellular
alteration
in
males,
hepatocellular
neoplasm(
s)
(including
adenoma,
sarcoma,
carcinoma,
leukemia,
and
lymphoma)
in
females,
and
singular
hepatocellular
adenoma
in
females.
Focus/
foci
of
cellular
alteration
were
observed
in
males
at
2500
(11.3%
vs
5.0%)
and
10,000
ppm
(24.1%)
and
females
at
10,000
ppm
(12.5%
vs
3.8%)
beginning
at
Week
57.
Singular
hepatocellular
adenoma
was
observed
in
the
10,000
ppm
females
(7.5%
vs
2.5%)
beginning
at
Week
77.
Hepatocellular
neoplasm(
s)
were
observed
in
the
10,000
ppm
females
(8.8%
vs
2.5%).
A
carcinoma
in
the
10,000
ppm
treatment
groups
was
first
observed
at
Week
65.
The
incidence
of
carcinomas
were
within
historical
control
ranges
for
each
sex,
while
the
incidence
of
adenomas
were
increased
by
3.21%
in
the
10,000
ppm
females.
A
dose
dependent
increase
in
adenomas
was
not
observed
in
males.
The
Health
Effects
Division
Carcinogenicity
Peer
Review
Committee
(CPRC)
concluded
that
hexazinone
should
be
classified
as
a
Group
D
(not
classifiable
as
to
human
carcinogenicity)(
7/
27/
94).
Under
the
conditions
of
this
study,
evidence
of
carcinogenic
potential
was
equivocal:
a
positive
trend
test
for
neoplasia
was
observed
in
female
mice,
but
no
significant
difference
was
determined
by
pair
wise
comparison.
The
submitted
study
is
classified
as
acceptable
for
guideline
870
4200
carcinogenicity
study
in
mice.
Discussion
of
Tumor
Data:
A
dose
dependent
increase
in
adenomas
was
not
observed
in
males.
Under
the
conditions
of
this
study,
evidence
of
carcinogenic
potential
was
equivocal:
a
positive
trend
test
for
neoplasia
was
observed
in
female
mice,
but
no
significant
difference
was
determined
by
pair
wise
comparison.
Adequacy
of
the
Dose
Levels
Tested:
Adequate
dose
levels
were
used
in
male
and
female
mice
to
test
for
the
carcinogenic
potential
of
hexazinone.
Liver
toxicity
was
seen
at
the
top
dose
level
in
males
and
females.
3.
Classification
of
Carcinogenic
Potential
HED's
Carcinogenicity
Peer
Review
Committee
classified
hexazinone
as
a
Group
D
Chemical
20
(not
classifiable
as
to
human
carcinogenicity)
(7/
27/
94).
This
classification
was
based
on
the
following
weight
of
evidence
considerations.
In
rats,
females
showed
no
evidence
for
carcinogenicity;
males
showed
a
significant
trend
only
for
thyroid
adenomas.
In
mice,
the
evidence
of
carcinogenicity
was
equivocal:
a
positive
trend
test
for
liver
tumors
was
observed
in
female
mice,
but
no
significant
difference
was
seen
by
pair
wise
comparison
(CPRC
Report
dated
July
27,
1994).
IV.
MUTAGENICITY
Adequacy
of
data
base
for
Mutagenicity:
The
data
base
for
mutagenicity
is
considered
adequate
based
on
pre
1991
mutagenicity
guidelines.
There
is
low
concern
for
mutagenic
potential
of
hexazinone.
Hexazinone
was
found
to
be
positive
for
mutagenicity
in
one
chromosomal
aberration
assay
(in
vitro
cytogenics)
(MRID#
00130709),
but
negative
in
the
remaining
studies.
It
is
concluded
that
the
test
material
was
clastogenic
in
both
of
the
non
activated
trials
and
was
also
clastogenic
in
the
one
adequate
S9
activated
trials.
Under
both
test
conditions,
concentrations
providing
evidence
of
clastogenicity
induced
an
acceptable
level
of
cytotoxicity
(>
50%
relative
cell
survival).
Thus,
the
findings
can
not
be
considered
to
be
a
secondary
effect
of
cytotoxicity.
Nevertheless,
the
outcome
of
the
induced
structural
damage
(i.
e.,
primarily
chromatid
and
chromosome
breaks)
is
unclear
since
these
types
of
structural
aberrations
would
not
likely
be
passed
on
to
daughter
cells.
Because
unambiguous
positive
results
were
achieved,
it
was
concluded
that
the
study
provided
adequate
evidence
that
INA
3674
112
(hexazinone,
technical)
is
clastogenic
in
an
acceptable
study.
Gene
Mutation
1.
Guideline
870.5100,
Reverse
mutation
in
Salmonella
EXECUTIVE
SUMMARY:
In
a
reverse
gene
mutation
assay
in
bacteria
(MRID
40826201),
strains
TA98,
TA100,
TA1535,
TA1537
and
TA1538
of
S.
typhimurium
were
exposed
to
Striazine
2,4(
1H,
3H)
dione,
3
cyclohexyl
6
dimethylamino
1
methyl
(95%
a.
i.)
in
ethanol
at
concentrations
of
200,
400,
600,
800
and
1000
:
g/
plate
without
mammalian
metabolic
activation
(S9
mix)
and
at
concentrations
of
400,
800,
1200,
1600
and
2000
:
g/
mL
with
S9
mix.
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
male
Crl:
CD(
SD)
BR
rat
liver.
The
maximum
concentrations
of
S
triazine
2,4(
1H,
3H)
dione,
3
cyclohexyl
6
dimethylamino1
methyl
tested
produced
little
or
no
cytotoxicity,
were
not
limited
by
solubility
and
were
not
a
limit
dose
for
the
assay.
No
statistically
significant
increases
in
the
number
of
revertants
per
plate
or
positive
linear
dose
response
were
seen.
The
solvent
and
positive
controls
induced
acceptable
responses
in
the
corresponding
strains.
There
was
no
evidence
of
induced
mutant
colonies
over
background.
This
study
is
classified
as
Unacceptable.
It
does
not
satisfy
the
requirement
for
FIFRA
Test
21
Guideline
[OPPTS
870.5100
(§
84
2)]
for
in
vitro
mutagenicity
[bacterial
reverse
gene
mutation]
data
and
should
have
used
higher
doses.
2.
Guideline
870.5300,
Gene
mutation
at
HGPRT
locus
EXECUTIVE
SUMMARY:
In
a
mammalian
cell
gene
mutation
assay
at
the
HGPRT
locus
(MRID
No.
00076956),
Chinese
hamster
CHO
K1
BH4
cells
cultured
in
vitro
were
exposed
to
INA
3674
112,
(Lot
No.
7612
5E6E,
95%
a.
i.)
in
ethanol
in
two
trials.
Concentrations
used
in
Trial
1
were
2.0,
11.1,
13.1,
13.9
and
14.3
mM
under
nonactivated
conditions
and
concentrations
of
2.0,
7.9,
8.9,
9.3
and
9.9
mM
under
activated
conditions
(S9
mix).
Concentrations
used
in
Trial
2
were
2.0,
5.9,
11.1,
13.1
and
13.9
mM
without
S9
mix
and
concentrations
of
2.0,
7.9,
8.9,
9.3
and
9.9
mM
with
S9
mix.
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
male
Charles
River
CD®
rat
livers.
INA
3674
112
was
tested
up
to
cytotoxic
concentrations.
In
Trial
1,
the
cultures
treated
at
14.3
mM
were
not
plated
for
mutation
determination
due
to
cytotoxicity
and
in
both
Trials
1
and
2,
those
cultures
treated
at
13.9
mM
were
excluded
from
analysis
because
no
mutants
were
seen.
No
statistically
significant
increases
in
mutant
frequency
over
solvent
control
values
were
seen
with
or
without
S9
mix
in
either
Trial
1
or
2.
The
expected
marked
increase
in
the
mutation
were
seen
with
the
positive
controls.
There
was,
however,
no
indication
that
INA
3674
112
induced
a
mutagenic
effect
either
in
the
presence
or
the
absence
of
S9
activation.
This
study
is
classified
as
acceptable.
It
satisfies
the
requirement
for
FIFRA
Test
Guideline
OPPTS
[870.5300
(§
84
2)]
for
in
vitro
mutagenicity
(mammalian
forward
gene
mutation)
data.
Chromosomal
Aberrations
3.
Guideline:
870.5375:
In
vitro
mammalian
cytogenics
(chromosomal
aberrations)
in
Chinese
hamster
CHO
cells.
EXECUTIVE
SUMMARY:
In
a
mammalian
cell
cytogenetics
assay
(MRID
No.
00130709),
Chinese
hamster
ovary
CHO
K1
BH4
cell
cultures
were
exposed
to
INA
3674
112
(Hexazinone,
95%
a.
i.)
in
ethanol
in
two
separate
trials.
Exposure
was
for
two
hours
with
activation
and
for
10
hours
without
activation.
Cells
were
harvested
10
hours
after
the
start
of
treatment.
In
Trial
1,
cells
were
treated
at
concentrations
of
1.58,
3.94,
15.85
and
19.82
mM
without
metabolic
activation
(S9
mix)
and
at
concentrations
of
0.32,
3.17,
7.93
and
15.85
mM
with
S9
mix.
In
Trial
2,
cells
were
treated
at
concentrations
of
1.58,
3.94,
7.93
and
15.85
without
S9
mix
and
at
concentrations
of
0.32,
3.17,
7.93
and
15.85
mM
with
S9
mix.
The
S9
fraction
was
obtained
from
Aroclor
1254
induced
CD
rat
livers.
INA
3674
112
was
tested
up
to
cytotoxic
concentrations.
Based
on
the
results
of
a
preliminary
cytotoxicity
test,
upper
concentrations
of
23.78
mM
without
S9
mix
and
47.56
mM
with
S9
mix
were
selected
for
the
first
cytogenetic
assay
but
these
concentrations
proved
excessively
cytotoxic
and
were
not
scored
for
chromosomal
aberrations.
Without
S9
activation,
statistically
significant
increases
(p<
0.01)
in
structural
aberrations
per
cell
(excluding
gaps),
lesions
per
cell
and
percent
abnormal
cells
were
seen
at
15.85
mM
(Trials
1
and
2)
and
19.82
mM
(tested
in
Trial
1
only).
Relative
percent
survival
(RPS)
at
this
level
was
.
50%.
The
percent
abnormal
cells
averaged
over
all
cultures
from
both
trials
was
28.0%
and
21.5%
at
19.82
and
15.85
mM,
respectively,
compared
to
the
solvent
control
values
of
2.0%
(0.5%
ethanol
in
Trial
2)
and
7.0%
(0.75%
ethanol
in
Trial
1).
The
percent
abnormal
cells
in
positive
control
cultures
was
18%
in
both
Trial
22
1
(4.83
mM
EMS)
and
Trial
2
(6.44
mM
EMS).
In
the
presence
of
S9
mix,
no
statistically
significant
increases
in
chromosomal
aberration
induction
were
seen
in
Trial
1;
however,
very
low
positive
control
values
indicated
a
problem
with
the
S9
mix.
Statistically
significant
increases
were
seen
at
15.85
mM
in
Trial
2;
RPS
at
15.85
mM
was
75%.
There
was
a
statistically
significant
dose
related
trend
for
all
three
parameters.
The
statistically
significant
(p
<0.01)
increases
at
15.85
mM
remained
when
the
data
from
Trial
1
and
2
were
combined
(average
of
20%
abnormal
cells
compared
to
10%
for
the
solvent
control).
The
predominant
aberrations
with
or
without
S9
mix
were
chromatid
and
isochromatid
breaks.
Solvent
and
positive
controls
(except
the
positive
control
in
Trial
1
with
S9
mix)
induced
the
appropriate
responses.
INA3674
112
was
positive
for
the
induction
of
structural
chromosomal
aberrations
in
both
the
presence
and
absence
of
S9
mix.
This
study
is
classified
as
Acceptable/
guideline
and
satisfies
the
requirement
for
FIFRA
Test
4.
Guideline
870.5385:
In
vivo
cytogenics
assay
in
rat
bone
marrow
cells
EXECUTIVE
SUMMARY:
In
a
mammalian
cell
cytogenetics
assay
(MRID
00131355),
in
bone
marrow
cells
of
Sprague
Dawley
CD
rats,
three
rats/
dose/
sex/
harvest
time
were
exposed
to
H#
14,555
in
corn
oil
(
assumed
100%
a.
i.)
at
doses
of
100,
300
and
1000
mg/
kg
by
oral
gavage.
Bone
marrow
cells
were
harvested
at
6,
12,
24
and
48
hours
post
treatment.
The
highest
dose
tested
(1000
mg/
kg)
was
lethal.
A
major
limitation
of
this
study
was
the
number
of
animals
treated
and
the
number
of
cells
analyzed
per
animal.
At
most,
three
rats/
sex/
dose/
harvest
time
were
treated
with,
at
most,
50
cells
per
rat
analyzed.
Few
or
no
analyzable
cell
were
available
from
many
rats.
Positive
control
values
were
significantly
(p=
0.03)
increased.
There
was
no
evidence
that
H#
14,
14,555
induced
an
increase
in
the
incidence
of
chromosomal
aberrations
in
the
bone
marrow
cells
of
treated
animals.
This
study
is
classified
as
Unacceptable.
The
number
of
cells
analyzed
and
the
number
of
rats
treated
was
insufficient.
The
study
does
not
satisfy
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5385
(§
84
2)]
for
in
vivo
cytogenetic
mutagenicity
data.
5.
Guideline
870.5395:
Micronucleus
assay
in
mouse
bone
marrow
EXECUTIVE
SUMMARY:
In
a
Crl:
CD
1
(ICR)
BR
mouse
bone
marrow
micronucleus
assay
(MRID
45124401),
5
mice/
sex/
dose/
harvest
time
were
treated
orally
with
Hexazinone
25L
(Lot
No.
9912033,
25%
Hexazinone
a.
i.
(24.5%
by
analysis)
and
75%
inert
ingredients)
at
doses
of
1000,
2000
and
3000
mg/
kg.
Bone
marrow
cells
were
harvested
at
24
and
48
hours
posttreatment
and
examined
for
micronucleated
polychromatic
erythrocytes
(MPCEs).
The
vehicle
was
Milli
Q
®
water.
Signs
of
toxicity
noted
at
3000
mg/
kg
included:
death,
convulsions,
half
shut
eyes,
head
tilt,
irregular
respiration,
lethargy,
low
carriage,
pallor,
prostration,
uncontrollable
spinning,
shovelnosing
straining
up
on
toes
and
tremors.
Micronuclei
were
scored
in
bone
marrow
from
mice
treated
at
3000
mg/
kg
and
from
the
solvent
and
positive
controls.
Mice
from
the
two
lower
dose
23
groups
were
not
evaluated
for
micronuclei
induction.
No
statistically
significant
increases
in
the
frequency
of
MPCEs
or
in
the
PCE/
NCE
ratio
over
the
solvent
control
values
were
seen
in
either
sex
at
either
the
24
or
48
hour
harvest
time.
The
solvent
and
positive
control
values
were
appropriate
and
within
the
testing
laboratory's
historical
control
ranges.
There
was
no
evidence
that
Hexazinone
25L
induced
a
clastogenic
or
aneugenic
effect
in
bone
marrow
at
any
harvest
time.
This
study
is
classified
as
Acceptable/
Guideline.
It
satisfies
the
requirement
for
FIFRA
Test
Guideline
[OPPTS
870.5395
(§
84
2)]
for
in
vivo
cytogenetic
mutagenicity
data.
Other
genetic
Studies
6.
Guideline
8760.5550:
Unscheduled
DNA
synthesis
assay
in
rat
hepatocytes
EXECUTIVE
SUMMARY:
In
an
unscheduled
DNA
synthesis
assay
(MRID
00130708),
primary
rat
hepatocyte
cultures
were
exposed
to
INA
3674
112
(Lot
No.
7612
5E6E,
95%
a.
i.)
in
ethanol
for
18
hours
at
concentrations
of
1
x
10
5
,
1
x
10
4
,
1
x
10
3
,
1
x
10
2
,
0.1,
1.0,
10.0
and
30.0
mM
in
Trial
1
and
at
concentrations
of
1
x
10
5
,
1
x
10
4
,
1
x
10
3
,
1
x
10
2
,
0.1,
1.0,
5.0,
10.0
and
30.0
mM
in
Trial
2.
INA
3674
112
was
tested
up
to
the
highest
achievable
concentration
in
the
solvent.
Two
slides
per
dose,
25
cells
per
slide
were
evaluated
for
UDS
induction
in
Trial
1.
One
slide
per
dose,
25
cells
per
slide
were
evaluated
in
Trial
2.
The
author
did
not
report
that
the
slides
were
coded
prior
to
analysis.
The
average
net
nuclear
grain
counts
of
test
material
treated
cells
in
Trial
1
were
all
less
than
zero
with
the
exception
of
one
slide
at
1
x
10
5
mM
(0.1
±
9.6)
and
one
slide
at
1.0
mM
(1.6
±
5.2).
The
average
net
nuclear
grain
count
was
below
zero
for
all
test
material
concentrations
in
Trial
2
with
the
exception
of
0.1
mM
where
the
average
net
nuclear
grain
count
was
0.0
±
2.9.
The
criterion
for
a
positive
response
was
an
average
net
nuclear
grain
count
of
at
least
five
in
two
experiments
at
any
tested
concentration.
The
results
were
thus
negative.
The
number
of
cells
in
repair
was
not
reported.
The
solvent
and
positive
(DMBA)
controls
induced
the
appropriate
responses.
There
was
no
evidence
that
unscheduled
DNA
synthesis,
as
determined
by
radioactive
tracer
procedures
[nuclear
silver
grain
counts]
was
induced.
This
study
is
classified
as
Acceptable/
Guideline.
It
satisfies
the
requirement
for
FIFRA
Test
Guideline;
OPPTS
870.5550
[§
84
2]
for
other
genotoxic
mutagenicity
data.
Compliance
statements
were
not
provided.
V.
HAZARD
CHARACTERIZATION
Hexazinone
is
a
herbicide
used
to
control
a
broad
spectrum
of
weeds
including
woody
plants
in
alfalfa,
rangeland,
pastures,
woodlands,
pineapple,
sugarcane
and
blue
berries.
Non
crop
areas
include
ornamental
plants
and
forests.
Hexazinone
is
used
as
a
pre
emergent,
post
emergence
herbicide
as
well
as
by
direct
spray
and
soil
applications.
There
are
no
non
occupational
(residential)
uses.
Hexazinone
has
low
acute
toxicity
by
the
oral
(Category
III),
dermal
(Category
IV
)
and
inhalation
routes
(Category
III).
Primary
eye
irritation
is
severe,
causing
corneal
opacity
and
moderate
irritation
in
unwashed
eyes
(Category
I).
It
causes
mild
skin
irritation
and
is
classified
Category
IV
for
skin
irritation.
It
is
not
a
skin
sensitizer
in
the
Guinea
pig.
24
Body
weight
decrement
and
liver
toxicity
were
the
most
frequent
effects
shown
in
studies
with
hexazinone.
Liver
toxicity
was
seen
in
the
chronic
dog
and
mouse
studies.
Body
weight
decrement
was
seen
in
the
chronic
rat
studies
and
the
studies
on
reproduction.
In
a
reproduction
study,
pup
weight
decrement
occurred
at
the
same
dose
as
parental
body
weight
decrement.
No
reproductive
effects
were
seen
in
the
study
other
than
pup
weight
decrement.
The
rat
prenatal
study
showed
fetal
weight
decrement
and
possibly
renal
malformations
but
no
increased
susceptibility.
The
new
rabbit
study
showed
fetal
weight
decrement
at
the
same
dose
causing
maternal
weight
decrement.
Thus,
no
offspring
susceptibility
is
seen
in
rat
or
rabbit
prenatal
studies
or
the
rat
reproduction
study.
The
21
day
dermal
study
in
the
rabbit
showed
no
systemic
toxicity
and
mild
dermal
irritation
at
the
limit
dose.
The
chronic
study
in
dogs
showed
severe
body
weight
decrement,
changes
in
liver
related
clinical
chemistry
values,
and
microscopic
lesions.
Body
weight
decrement
was
seen
in
a
chronic
carcinogenicity
studies
in
rats
and
mice.
Liver
toxicity
was
seen
in
mice.
The
mouse
carcinogenicity
study
showed
an
increased
trend
for
liver
carcinomas,
but
no
pair
wise
significant
increases.
The
rat
study
showed
no
carcinogenic
potential.
Based
on
these
studies
in
rats
and
mice,
hexazinone
was
classified
in
a
group
D,
not
classifiable
as
a
carcinogen.
Mutagenicity
is
of
low
concern.
A
reverse
mutation
assay
was
unacceptable,
but
the
potential
concern
is
mitigated
by
an
negative
in
vivo
mutation
assay
and
the
remaining
negative
studies
on
potential
genetic
damage.
Rat
metabolism
studies
showed
that
hexazinone
was
rapidly
absorbed
and
excreted
and
essentially
no
difference
in
the
metabolism
of
males
and
females
at
high
or
low
dose
levels.
Almost
no
parent
hexazinone
was
recovered
in
urine
or
feces.
Two
major
metabolites
were
recovered
from
feces
and
urine,
in
addition
to
lesser
amounts
of
a
third
metabolite
and
small
amounts
conjugated
products
from
urine.
25
VI.
DATA
REQUIREMENTS
The
HIARC
requested
a
28
day
inhalation
study
with
hexazinone
as
confirmation.
There
was
concern
for
potential
inhalation
exposure
based
on
the
use
pattern.
A
1976
21
day
inhalations
study
in
rats
(MRID#
00063972)
was
considered
unacceptable
as
documented.
VII.
ACUTE
TOXICITY
Acute
Toxicity
of
Hexazinone
Guideline
No.
Study
Type
MRIDs
#
Results
Toxicity
Category
81
1
Acute
Oral/
Rat
41235004
(1989)
LD50
=
1200
mg/
kg
III
81
2
Acute
Dermal/
Rabbit
00104974
LD50
>5278
mg/
kg
IV
81
3
Acute
Inhalation
41756701
(1990)
LC50
>
3.94
mg/
L(
4
hour)
1
III
81
4
Primary
Eye
Irritation
00106003
(1982)
Irreversible
corneal
opacity,
Severe
I
81
5
Primary
Skin
Irritation
00106004
(1982)
Mild
IV
81
6
Dermal
Sensitization
41235005
(1989)
NA
Not
a
skin
sensitizer
81
8
Acute
Neurotoxicity
Not
conducted
1
These
effects
are
consistent
with
an
unreviewed
and
unacceptable
three
week
inhalation
study
with
dust
[(
MRID#
00063972
(1976);
summary
only
submitted]
reporting
no
significant
toxic
effects
at
2.5
mg/
L,
the
only
dose
tested.
26
VII.
Summary
of
Toxicological
Dose
and
Endpoints
for
HEXAZINONE
Exposure
Scenario
Dose
(mg/
kg/
day)
UF
/MOE
Hazard
Based
Special
FQPA
Safety
Factor
Endpoint
for
Risk
Assessment
Dietary
Risk
Assessments
Acute
Dietary
females
13
50
years
of
age
NOAEL
=
400
UF
=
100
Acute
RfD
=
4.0
mg/
kg/
day
1x
Developmental
Toxicity
Rat
LOAEL
is
900
mg/
kg/
day
based
on
decreased
male
and
female
fetal
weight,
kidneys
with
no
papilla
(malformation)
and
misaligned
sternebrae
(variation)
Acute
Dietary
general
population
including
infants
and
children
An
appropriate
endpoint
attributable
to
a
single
dose
was
not
identified
in
the
oral
studies
for
general
population,
including
the
rat
and
rabbit
developmental
studies.
Chronic
Dietary
all
populations
NOAEL=
5.0
UF
=
100
Chronic
RfD
=
0.05
mg/
kg/
day
1x
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Incidental
Oral
Short
Term
(1
30
Days)
Residential
Only
There
are
no
residential
uses
at
the
present
time
and
therefore,
endpoints
were
not
selected.
Incidental
Oral
Intermediate
Term
(1
6
Months)
Residential
Only
There
are
no
residential
uses
at
the
present
time
and
therefore,
endpoints
were
not
selected.
Non
Dietary
Risk
Assessments
Dermal
Short
Term
(1
30
days)
No
hazard
was
identified,
therefore
quantification
of
risk
is
not
required.
No
systemic
toxicity
was
seen
at
the
limit
dose
following
repeat
dermal
application,
and
there
were
no
concerns
for
pre
and/
or
post
natal
toxicity.
Residential
Not
Applicable
Occupational
Not
Applicable
Dermal
Intermediate
Term
1
(1
6
Months)
Oral
NOAEL=
5.0
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Residential
MOE=
Not
Applicable
Not
Applicable
Occupational
MOE=
100
Not
Applicable
Exposure
Scenario
Dose
(mg/
kg/
day)
UF
/MOE
Hazard
Based
Special
FQPA
Safety
Factor
Endpoint
for
Risk
Assessment
27
Dermal
Long
Term
1
(1
6
Months)
Oral
NOAEL=
5.0
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Residential
MOE=
Not
Applicable
Occupational
MOE=
100
Not
Applicable
Inhalation
Short
Term
2
(1
30
days)
Oral
NOAEL=
100
Developmental
Toxicity
Rabbit
LOAEL
=
50
mg/
kg/
day
based
on
decreases
in
maternal
food
consumption
and
dose
related
body
weight
decrement
and
fetal
weight
decrement.
Residential
MOE=
Not
Applicable
Not
Applicable
Occupational
MOE=
100
Not
Applicable
Inhalation
Intermediate
Term
(1
6
Months)
Oral
NOAEL=
5.0
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
mg/
kg/
day,
male;
37.57
mg/
kg/
day,
female,
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Residential
MOE
=Not
Applicable
Not
Applicable
Occupational
MOE=
100
Not
Applicable
Inhalation
Long
Term
(>
6
Months)
Oral
NOAEL=
5.0
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
mg/
kg/
day,
male
;37.57
mg/
kg/
day,
female,
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Residential
MOE=
Not
Applicable
Not
Applicable
Occupational
MOE=
100
Not
Applicable
Cancer
Classification:
D
Not
Classifiable
as
to
human
carcinogenicity
1
Since
an
oral
NOAEL
was
selected
12.5%
dermal
absorption
factor
should
be
used
for
route
to
route
exposures.
2
Absorption
via
the
inhalation
route
is
assumed
to
be
equivalent
to
oral
absorption.
| epa | 2024-06-07T20:31:42.954794 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0023/content.txt"
} |
EPA-HQ-OPP-2002-0188-0024 | Supporting & Related Material | "2002-09-16T04:00:00" | null | TXR
NO.
0051049
August
08,
2002
MEMORANDUM
SUBJECT:
HEXAZINONE
2
nd
Report
of
the
FQPA
Safety
Factor
Committee.
NOTE:
THIS
REPORT
REPLACES
THE
PREVIOUS
REPORT
OF
THE
FQPA
SAFETY
FACTOR
COMMITTEE
DATED
MAY
15,
2002
(HED
DOC.
NO.
0050750).
FROM:
Brenda
Tarplee,
Executive
Secretary
FQPA
Safety
Factor
Committee
Health
Effects
Division
(7509C)
THROUGH:
Ed
Zager,
Chairman
FQPA
Safety
Factor
Committee
Health
Effects
Division
(7509C)
TO:
Carol
Christensen,
Risk
Assessor
Reregistration
Branch
2
Health
Effects
Division
(7509C)
PC
Code:
107201
The
Health
Effects
Division
(HED)
FQPA
Safety
Factor
Committee
(SFC)
met
on
August
5,
2002
to
reevaluate
the
hazard
and
exposure
data
for
Hexazinone
with
regard
to
making
a
decision
on
the
additional
safety
factor
for
the
protection
of
infants
and
children.
The
SFC
concluded
that,
based
on
reliable
data,
no
additional
safety
factor
is
necessary
to
protect
the
safety
of
infants
and
children
in
assessing
Hexazinone
exposures
and
risks.
This
report
replaces
the
previous
report
of
the
FQPA
Safety
Factor
Committee
dated
May
15,
2002
(HED
Doc.
No.
107201).
2
I.
HAZARD
ASSESSMENT
On
July
30,
2002,
the
Hazard
Identification
Assessment
Review
Committee
(HIARC)
reevaluated
the
toxicity
endpoints
selected
for
Hexazinone
risk
assessment
as
well
as
the
FQPA
assessment
in
light
of
newly
reviewed
data:
rabbit
developmental
toxicity
study.
The
following
summarizes
the
conclusions
of
the
committee
at
this
meeting.
1.
Adequacy
of
the
Toxicology
Database
On
July
30,
2002,
the
HIARC
concluded
that
the
toxicology
data
base
for
Hexazinone
contains
acceptable
guideline
prenatal
developmental
toxicity
studies
in
the
rat
and
the
rabbit
as
well
as
an
acceptable
guideline
2
generation
reproduction
study
conducted
in
rats.
In
addition,
the
HIARC
concluded
that
a
developmental
neurotoxicity
study
with
Hexazinone
is
not
required.
2.
Determination
of
Susceptibility
The
data
provided
no
indication
of
increased
susceptibility
of
rats
or
rabbits
to
in
utero
and/
or
postnatal
exposure
to
Hexazinone.
The
recently
submitted
rabbit
developmental
study
showed
fetal
weight
decrement
at
the
same
dose
as
maternal
weight
decrement.
3.
Degree
of
Concern
and
Residual
Uncertainties
The
HIARC
concluded
that
there
are
no
residual
uncertainties
for
pre
and/
or
post
natal
toxicity
in
any
of
the
available
studies
with
Hexazinone.
II.
EXPOSURE
ASSESSMENT
No
changes
were
made
in
the
exposure
assessment
since
the
last
review
for
Hexazinone.
1.
Dietary
(Food)
Exposure
Considerations
(Correspondence:
C.
Christensen
to
B.
Tarplee
dated
April
3,
2002
and
May
1,
2002;
dietary
food
responses
provided
by
S.
Kinard
and
J.
Punzi)
Hexazinone
is
a
contact
and
residual
herbicide
used
to
control
many
annual,
biennial
and
perennial
weeds
and
woody
plants.
Tolerances
are
currently
established
for
combined
residues
of
Hexazinone
and
its
metabolites
in
or
on
alfalfa,
pasture
and
range
grasses,
blueberries,
pineapple,
sugarcane,
molasses,
milk
and
meat
(40
CFR§
180.396).
On
January
29,
2002
and
March
12,
2002,
the
HED
Metabolism
Assessment
Review
Committee
(MARC)
met
to
determine
which
metabolites
should
be
included
in
the
tolerance
expression
and
risk
assessment
for
Hexazinone.
The
MARC
concluded
that:
parent
plus
metabolites
A,
B,
C,
D,
and
E
(calculated
as
Hexazinone)
are
the
residues
of
concern
to
be
included
in
tolerance
expression
and
risk
assessment
for
plants
and
rotational
crops.
Additionally,
the
residues
of
concern
to
be
included
in
the
tolerance
expression
for
ruminants
are
Hexazinone
plus
metabolites
B,
C,
C
2,
and
F
in
milk,
and
3
Hexazinone
plus
metabolites
B
and
F
in
tissue.
For
purposes
of
risk
assessment,
the
residues
of
concern
in/
on
ruminants
are
Hexazinone
plus
metabolites
B,
C,
C
1,
C
2,
and
F
(April
3,
2002;
Draft
memo
provided
to
FQPA
SFC).
The
HED
Dietary
Exposure
Evaluation
Model
(DEEM)
is
used
to
assess
the
risk
from
dietary
exposure
to
Hexazinone
residues
in
food.
These
are
currently
Tier
1
analyses
based
on
tolerance
level
residues
and
assuming
that
100%
of
crops
are
treated
with
Hexazinone.
Since
there
are
data
gaps
for
the
magnitude
of
the
residues
of
Hexazinone
and
metabolites
A,
B,
C,
D,
and
E
in/
on
pasture
and
range
grass
(forage
and
hay),
tolerances
established
for
these
feed
items
and
for
secondary
residues
in/
on
milk
and
meat,
cannot
be
reassessed.
Therefore,
HED
is
recommending
that
the
use
on
pasture
and
range
grasses
be
discontinued
and
that
tolerances
resulting
from
these
uses
be
revoked.
The
FQPA
SFC
based
its
safety
factor
recommendation
on
the
assumption
that
the
use
of
Hexazinone
on
pasture
and
range
grasses
is
withdrawn
and
all
established
tolerances
associated
with
this
use
are
revoked.
2.
Dietary
(Drinking
Water)
Exposure
Considerations
(Correspondence:
C.
Christensen
to
B.
Tarplee
dated
April
3,
2002;
dietary
water
responses
provided
by
J.
Melendez
and
L.
Liu)
The
environmental
fate
database
is
adequate
and
indicate
that
Hexazinone
is
persistent
and
mobile
in
soil
and
aquatic
environments.
The
mobility
of
Hexazinone
was
demonstrated
in
batch
equilibrium
data
and
confirmed
in
field
and
forestry
dissipation
data.
The
batch
equilibrium
data
also
suggest
that
its
degradates
are
very
mobile.
Therefore,
Hexazinone
and
its
degradates
may
be
of
concern
for
surface
water
and
groundwater
contamination.
On
January
29,
2002
and
March
12,
2002,
the
HED
Metabolism
Assessment
Review
Committee
(MARC)
concluded
that
Hexazinone,
G3170,
and
all
metabolites
with
conjoined
cyclohexyl
and
triazine
rings
should
be
included
in
the
drinking
water
risk
assessment
for
Hexazinone.
The
following
degradates
were
detected
in
the
laboratory
fate
studies
and/
or
monitored
in
the
field
dissipation
and
the
groundwater
study:
A,
A
1,
C,
D,
1,
2,
and
G3170.
The
registrant
submitted
a
small
scale
prospective
groundwater
monitoring
study
for
Hexazinone.
The
study
was
conducted
in
a
field
of
alfalfa
underlain
with
sandy
soil
in
Merced
County,
California.
The
site
is
located
within
the
recharge
area
for
a
shallow
unconfined
aquifer.
The
organic
matter
content
of
the
soil
was
#
0.7%,
the
pH
was
7.5
8.9
in
the
upper
1.5
feet,
and
there
were
no
continuous
impeding
layers.
Results
indicated
that
Hexazinone
and
its
degradates
are
very
mobile
and
persistent.
The
maximum
total
residue
detected
in
the
groundwater
study
is
used
in
the
risk
assessment
and
is
supported
by
modeling
output.
4
The
Board
of
Pesticides
Control
in
the
Department
of
Agriculture,
Food
and
Rural
Resources
in
the
State
of
Maine
conducted
a
statewide
assessment
to
determine
the
impact
of
highly
leachable
pesticides
(including
Hexazinone,
a
herbicide
used
in
the
production
of
blueberries)
on
surface
water
and
ground
waters
in
Maine.
Although
the
total
amounts
of
Hexazinone
used
on
blueberries
in
Maine
is
very
low
(only
approximately
1%
of
the
total
sale
in
the
U.
S.),
the
chemical
was
detected
in
groundwater
and
surface
water
at
very
high
frequency.
Degradate
B
was
also
detected
in
surface
water
and
groundwater;
however,
no
detailed
information
was
provided.
Tier
I
modeling
was
used
to
estimate
the
maximum
concentrations
of
Hexazinone
likely
to
be
found
in
surface
(FIRST)
and
ground
(SCIGROW)
waters.
The
models
used
take
into
consideration
the
percent
area
crop
and
the
index
reservoir.
Because
of
the
high
mobility
of
Hexazinone,
and
its
high
solubility,
it
appears
that
the
chemical
may
be
preferentially
dissolved
in
the
ponds,
rivers
and
reservoirs
(as
opposed
to
adsorbed
to
sediments).
It
is
noted
that
the
SCIGROW
result
obtained
is
of
the
same
order
of
magnitude
than
the
results
obtained
in
the
prospective
groundwater
study.
3.
Residential
Exposure
Considerations
(Correspondence:
C.
Christensen
to
B.
Tarplee
dated
April
3,
2002)
There
are
currently
no
registered
residential
uses
of
Hexazinone.
III.
SAFETY
FACTOR
RECOMMENDATION
AND
RATIONALE
1.
FQPA
Safety
Factor
Recommendations
The
FQPA
SFC
recommends
that
OPP
depart
from
the
default
10X
additional
safety
factor
and
instead
use
a
different
additional
safety
factor
of
1X.
This
recommendation
is
based
on
reliable
data
supporting
the
findings
set
forth
below.
A.
Traditional
Additional
Safety
Factor
(Addressing
Data
Deficiencies)
On
July
30,
2002,
the
HIARC
found
no
data
deficiencies
and
hence
concluded
that
no
additional
traditional
safety
factors
were
needed
with
regard
to
the
completeness
of
the
Hexazinone
toxicity
database
(See
Section
I.
1.).
B.
Special
FQPA
Safety
Factors
The
FQPA
SFC
recommended,
that
no
Special
FQPA
Safety
Factor
is
necessary
to
protect
the
safety
of
infants
and
children
in
assessing
Hexazinone
exposure
and
risks.
2.
Rationale
and
Findings
Regarding
Recommendation
on
Special
FQPA
Safety
Factor
The
Committee
concluded
that
no
Special
FQPA
safety
factor
was
needed
because:
5
The
toxicology
database
for
Hexazinone
contains
acceptable
guideline
developmental
and
reproduction
studies
and
these
studies
demonstrate
that
there
is
no
concern
for
quantitative
or
qualitative
increased
susceptibility
of
the
young.
The
HIARC
concluded
that
a
developmental
neurotoxicity
study
with
Hexazinone
is
not
required.
There
are
no
residual
uncertainties
identified
in
the
exposure
databases.
The
dietary
food
exposure
assessment
is
Tier
1,
screening
level,
which
is
based
on
tolerance
level
residues
and
assumes
100%
of
all
crops
are
treated
with
Hexazinone.
The
dietary
drinking
water
assessment
uses
monitoring
data
(ground
water)
and
modeling
results
(surface
water)
based
on
chemical
specific
data
and
include
extrapolated
estimates
for
all
degradates
of
concern.
These
assessments
will
not
underestimate
the
exposure
and
risks
posed
by
Hexazinone.
NOTE:
This
safety
factor
recommendation
is
based
on
the
assumption
that
the
use
of
Hexazinone
on
pasture
and
range
grasses
is
withdrawn
(due
to
the
lack
of
field
trial
residue
data
for
forage
and
hay)
and
that
all
established
tolerances
associated
with
this
use
are
revoked.
3.
Application
of
the
FQPA
Safety
Factors
(Population
Subgroups
/
Risk
Assessment
Scenarios)
The
FQPA
SFC
recommends
that
no
Special
FQPA
Safety
Factor
is
necessary
to
protect
the
safety
of
infants
and
children
in
assessing
Hexazinone
exposure
and
risks.
This
recommendation
is
applicable
to
all
population
subgroups
for
all
exposure
routes
and
durations.
No
other
FQPA
safety
factor
would
be
appropriate
for
Hexazinone.
6
4.
Summary
of
FQPA
Safety
Factors
Summary
of
FQPA
Safety
Factors
for
Hexazinone
LOAEL
to
NOAEL
(UFL)
Subchronic
to
Chronic
(UFS)
Incomplete
Database
(UFDB)
Special
FQPA
Safety
Factor
(Hazard
and
Exposure)
Magnitude
of
Factor
1X
1X
1X
1X
Rationale
for
the
Factor
No
LOAEL
to
NOAEL
extrapolations
performed
No
subchronic
to
Chronic
extrapolations
performed
Database
is
sufficiently
complete
to
assess
risks
to
infants
and
children.
No
residual
concerns
regarding
pre
or
post
natal
toxicity
or
completeness
of
the
toxicity
or
exposure
databases
Endpoints
to
which
the
Factor
is
Applied
Not
Applicable
Not
Applicable
Not
Applicable
Not
Applicable
| epa | 2024-06-07T20:31:42.964596 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0024/content.txt"
} |
EPA-HQ-OPP-2002-0188-0025 | Supporting & Related Material | "2002-09-16T04:00:00" | null | [Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
1
of
9
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
05/
14/
2002
revised
07/
30/
2002
SUBJECT:
Hexazinone
Acute
and
Chronic
Dietary
Exposure
Assessments
for
the
TRED.
PC
Code:
107201
DP
Barcode:
D279898
REVIEWER:
John
S.
Punzi,
Ph.
D.,
Chemist
Reregistration
Branch
II
Health
Effects
Division
(7509C)
THROUGH:
Richard
Griffin,
DESAC
Reviewer
Branch/
Health
Effects
Division
(7509C)
Alan
Nielsen,
Branch
Senior
Scientist
Branch/
Health
Effects
Division
(7509C)
TO:
Dirk
Helder,
Chemical
Review
Manager
Reregistration
Branch
II
Special
Review
and
Reregistration
Division
(7509C)
and
Carol
Christensen,
Risk
Assessor
Reregistration
Branch
II
Health
Effects
Division
(7509C)
Executive
Summary
The
purpose
of
this
memorandum
is
to
report
the
revised
results
of
a
Tier
1
dietary
exposure
analysis
for
hexazinone.
In
this
analysis
the
acute
and
chronic
dietary
exposure
and
risk
estimates
resulting
from
food
intake
were
determined
for
the
U.
S.
population
and
various
population
subgroups.
[Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
2
of
9
Acute
and
chronic
dietary
exposure
assessments
were
performed
in
order
to
determine
the
exposure
and
risk
estimates
which
result
from
the
use
of
hexazinone
on
the
crops
included
in
the
reregistration
eligibility
decision.
The
document
has
been
revised
to
reflect
a
07/
30/
02
HIARC
revist.
Hexazinone
residues
of
concern
for
plants
are
parent
plus
metabolites
A,
B,
C,
D,
E
(see
D279897,
S.
Kinard,
02/
05/
2002,
for
structures
and
metabolite
discussion).
The
tolerance
values
for
hexazinone
in/
on
blueberry,
pineapple,
and
sugarcane
are
based
on
the
enforcement
analytical
method's
limit
of
quantitation
(LOQ)
and
all
non
detectable
residues
were
found
in
residue
studies
(see
D279899,
J.
Punzi,
05/
15/
2002).
This
analysis
used
a
single
residue
estimate
based
on
the
reassessed
tolerance
for
blueberry,
pineapple,
and
sugarcane.
Default
processing
factors
and
100%
crop
treated
were
used
for
residue
input
into
DEEM.
Hexazinone
residues
of
concern
in
ruminant
milk
are
hexazinone
plus
metabolites
B,
C,
C
2,
and
F.
Hexazinone
residues
of
concern
in
ruminant
tissue
are
hexazinone
plus
metabolites
B
and
F.
For
purposes
of
risk
assessment
however,
the
residues
of
concern
in
livestock
milk
and
tissue
are
hexazinone
plus
metabolites
B,
C,
C
1,
C
2,
and
F.
The
livestock
feeding
study
indicates
significant
residues
in
milk
at
all
feeding
levels
and
quantifiable
residues
in
kidney.
When
the
residue
levels
are
corrected
for
exaggerated
rates
the
values
are
less
than
the
sum
of
the
LOQ's
for
the
residues
of
concern.
Based
on
the
analytical
method's
LOQ
the
residue
estimate
for
meats
and
milk
are
0.24
ppm.
Default
processing
factors
and
100%
crop
treated
were
used
for
residue
input
into
DEEM.
The
chronic
dietary
risk
estimates
are
provided
for
the
U.
S.
population
(total)
and
various
population
subgroups.
This
assessment
concludes
that
the
exposure
is
below
HED's
level
of
concern
for
all
population
subgroups
examined.
Exposures,
as
a
percentage
of
the
RfD,
ranged
from
approximately
3%
for
females
aged
13
through
50
years
to
15%
for
children
aged
1
through
6
years.
The
acute
dietary
risk
estimates
are
provided
for
the
population
subgroup
consisting
of
females
aged
13
through
50
years
only.
This
assessment
concludes
that
the
exposure
is
below
HED's
level
of
concern
for
this
subgroup.
Exposures
as
a
percentage
of
the
RfD
are
calculated
to
be
less
than
1%
at
the
95
th
percentile.
I.
Introduction
Dietary
risk
assessment
incorporates
both
exposure
and
toxicity
of
a
given
pesticide.
For
acute
and
chronic
assessments,
the
risk
is
expressed
as
a
percentage
of
a
maximum
acceptable
dose.
This
dose
is
the
highest
daily
dose
which
HED
has
deemed
will
pose
no
unreasonable
adverse
health
effects
and
is
called
the
population
adjusted
dose
(PAD).
The
PAD
is
equivalent
to
the
Reference
Dose
(RfD)
divided
by
the
FQPA
Safety
Factor.
Dietary
risk
is
expressed
as
a
percentage
of
the
PAD.
HED's
level
of
concern
is
exceeded
when
the
dietary
risk
exceeds
100%
of
the
PAD.
References
which
discuss
the
acute
and
chronic
risk
assessments
in
more
detail
are
available
on
the
EPA/
pesticides
web
site:
"Available
Information
on
Assessing
Exposure
from
[Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
3
of
9
Pesticides,
A
User's
Guide",
6/
21/
2000,
web
link:
http://
www.
epa.
gov/
fedrgstr/
EPA
PEST/
2000/
July/
Day
12/
6061.
pdf
;
or
see
SOP
99.6
(8/
20/
99).
II.
Residue
Information
Hexazinone
tolerances
are
established
under
40
CFR
§180.396
(a)
and
(b).
The
tolerance
for
plant
and
animal
commodities,
is
currently
expressed
in
terms
of
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone).
Tolerances
are
currently
established
for;
alfalfa;
alfalfa
hay;
blueberries;
cattle,
goat,
hog,
and
horse
fat,
meat,
and
meat
by
products;
range
grasses,
pasture
grasses,
milk,
pineapple
and
sugarcane.
Current
tolerances
range
from
0.1
ppm
in/
on
meats
and
milk
to
10
ppm
on
grasses.
Reassessed
tolerances
range
from
0.1
ppm
to
4
ppm.
Tolerances
are
not
currently
needed
for
livestock
fat,
hog
meat,
and
hog
meat
by
products.
HED
is
recommending
that
in
order
to
reassess
the
established
hexazinone
tolerances
for
milk
and
the
fat,
meat,
and
meat
byproducts
of
livestock
and
to
compute
a
maximum
theoretical
dietary
burden
(MTDB)
of
hexazinone
to
livestock,
uses
on
pasture
and
rangeland
grasses
must
be
revoked.
A
MTDB
could
not
be
calculated
including
grass
and
grass
hay
since
additional
residue
data
are
required
for
use
patterns
in
which
significant
residues
are
expected
in/
on
the
RACs.
HED
recognizes
that
the
estimated
100,000
acres
of
pasture
and
rangeland
treated
with
hexazinone
is
relatively
low.
Since
grass
and
grass
hay
are
considered
major
dietary
components
of
ruminants
(up
to
60%
of
the
diet
per
current
OPPTS
GLN)
a
MTDB
for
livestock
could
not
be
developed
when
grasses
are
included
in
the
registered
uses.
HED
has
determined
that
a
MTDB
could
be
constructed
from
other
potential
feed
items
for
livestock
and
subsequently
tolerances
for
meats
and
milk
can
be
reassessed.
Hexazinone
residues
of
concern
for
plants
are
parent
plus
metabolites
A,
B,
C,
D,
E
(see
D279897,
S.
Kinard
02/
05/
2002,
for
structures
and
metabolite
discussion).
The
tolerance
values
for
hexazinone
in/
on
blueberry,
pineapple,
and
sugarcane
are
based
on
the
analytical
method's
limit
of
quantitation
(LOQ)
and
all
non
detectable
residues
were
found
in
residue
studies
(see
D279899,
J.
Punzi,
05/
05/
2002).
This
analysis
used
a
single
residue
estimate
based
on
the
reassessed
tolerance
for
blueberry,
pineapple,
and
sugarcane.
Default
processing
factors
and
100%
crop
treated
were
used
for
residue
input
into
DEEM.
Hexazinone
residues
of
concern
in
ruminant
milk
are
hexazinone
plus
metabolites
B,
C,
C
2,
and
F.
Hexazinone
residues
of
concern
in
ruminant
tissue
are
hexazinone
plus
metabolites
B
and
F.
For
purposes
of
risk
assessment
however,
the
residues
of
concern
in
livestock
milk
and
tissue
are
hexazinone
plus
metabolites
B,
C,
C
1,
C
2,
and
F.
The
livestock
feeding
study
indicates
significant
residues
in
milk
at
all
feeding
levels
and
quantifiable
residues
in
kidney.
When
the
residue
levels
are
corrected
for
exaggerated
rates
the
values
are
less
than
the
sum
of
the
LOQ's
for
the
residues
of
concern.
Based
on
the
analytical
method's
LOQ
the
reside
estimate
for
meats
and
milk
are
0.24
ppm.
Default
processing
factors
and
100%
crop
treated
were
used
for
residue
input
into
DEEM.
[Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
4
of
9
Residue
Data
used
for
Acute
and
Chronic
Assessments:
This
TIER
1
analysis
used
a
single
residue
estimate
based
on
the
reassessed
tolerance
for
blueberry,
pineapple,
and
sugarcane.
Default
processing
factors
and
100%
crop
treated
were
used
for
residue
input
into
DEEM.
For
purposes
of
risk
assessment
however,
the
residues
of
concern
in
livestock
milk
and
tissue
are
hexazinone
plus
metabolites
B,
C,
C
1,
C
2,
and
F.
The
same
data
are
being
used
in
both
acute
and
chronic
analysis.
III.
DEEM™
Program
and
Consumption
Information
Hexazinone
acute
and
chronic
dietary
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(DEEM™)
software,
Version
[7.76],
which
incorporates
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intake
by
Individuals
(CSFII),
1989
1992.
The
1989
92
data
are
based
on
the
reported
consumption
of
more
than
10,000
individuals
over
three
consecutive
days,
and
therefore
represent
more
than
30,000
unique
"person
days"
of
data.
Foods
"as
consumed"
(e.
g.,
apple
pie)
are
linked
to
raw
agricultural
commodities
and
their
food
forms
(e.
g.,
apples
cooked/
canned
or
wheat
flour)
by
recipe
translation
files
internal
to
the
DEEM
software.
Consumption
data
are
averaged
for
the
entire
U.
S.
population
and
within
population
subgroups
for
chronic
exposure
assessment,
but
are
retained
as
individual
consumption
events
for
acute
exposure
assessment.
For
chronic
exposure
and
risk
assessment,
an
estimate
of
the
residue
level
in
each
food
or
foodform
(e.
g.,
orange
or
orange
juice)
on
the
commodity
residue
list
is
multiplied
by
the
average
daily
consumption
estimate
for
that
food/
food
form.
The
resulting
residue
consumption
estimate
for
each
food/
food
form
is
summed
with
the
residue
consumption
estimates
for
all
other
food/
food
forms
on
the
commodity
residue
list
to
arrive
at
the
total
average
estimated
exposure.
Exposure
is
expressed
in
mg/
kg
body
weight/
day
and
as
a
percent
of
the
cPAD.
This
procedure
is
performed
for
each
population
subgroup.
For
acute
exposure
assessments,
individual
one
day
food
consumption
data
are
used
on
an
individual
by
individual
basis.
The
reported
consumption
amounts
of
each
food
item
can
be
multiplied
by
a
residue
point
estimate
and
summed
to
obtain
a
total
daily
pesticide
exposure
for
a
deterministic
(Tier
1
or
Tier
2)
exposure
assessment,
or
"matched"
in
multiple
random
pairings
with
residue
values
and
then
summed
in
a
probabilistic
(Tier
3/
4)
assessment.
The
resulting
distribution
of
exposures
is
expressed
as
a
percentage
of
the
aPAD
on
both
a
user
(i.
e.,
those
who
reported
eating
relevant
commodities/
food
forms)
and
a
per
capita
(i.
e.,
those
who
reported
eating
the
relevant
commodities
as
well
as
those
who
did
not)
basis.
In
accordance
with
HED
policy,
per
capita
exposure
and
risk
are
reported
for
all
tiers
of
analysis.
However,
for
tiers
1
and
2,
significant
differences
in
user
vs.
per
capita
exposure
and
risk
are
identified
and
noted
in
the
risk
assessment.
HED
notes
that
there
is
a
degree
of
uncertainty
in
extrapolating
exposures
for
certain
population
subgroups
which
may
not
be
sufficiently
represented
in
the
consumption
surveys,
(e.
g.,
nursing
and
non
nursing
infants
or
Hispanic
females).
Therefore,
risks
estimated
for
these
[Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
5
of
9
subpopulations
were
included
in
representative
populations
having
sufficient
numbers
of
survey
respondents
(e.
g.,
all
infants,
or
females
13
50
years).
IV.
Toxicological
Information
The
toxicological
endpoint
summary
table
below
reflects
the
HIARC
document
(01/
16/
2002,
TXR#
0050371),
the
FQPA
SF
committee
report
(05/
15/
2002,
TXR#
0050750)
and
an
additional
HIARC
meeting
on
07/
30/
02.
Table
1.
Summary
of
Toxicological
Doses
and
Endpoints
for
[CHEMICAL]
for
Use
in
Dietary
Exposure
Assessment
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF*
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
[Female
13
50]
NOAEL
=
[400]
mg/
kg/
day
UF
=
[100]
Acute
RfD
=
[4.0]
mg/
kg/
day
FQPA
SF
=
[1]
aPAD
=[
4.0]
mg/
kg/
day
[Developmental
Toxicity
Rat]
LOAEL
=
[
900]
mg/
kg/
day
based
on
[decreased
fetal
weight,
malformation
of
kidneys]
Chronic
Dietary
all
populations
NOAEL=
[5]
mg/
kg/
day
UF
=
[100]
Chronic
RfD
=
[0.05]
mg/
kg/
day
FQPA
SF
=
[1]
cPAD
=
[0.05]
mg/
kg/
day
[Chronic
One
Year
Feeding
Dog]
LOAEL
=
[
~40]
mg/
kg/
day
based
on
[hepatotoxicity]
V.
Results/
Discussion
As
stated
above,
for
acute
and
chronic
assessments,
HED's
level
of
concern
is
exceeded
when
the
dietary
risk
exceeds
100%
of
the
PAD.
The
DEEM
analyses
can
estimate
the
dietary
exposure
of
the
U.
S.
population
and
26
population
subgroups.
The
results
reported
in
Table
2
are
for
the
appropriate
subpopulation,
females
aged
13
to
50
years.
The
results
reported
in
Table
3
are
for
the
U.
S.
Population
(total),
all
infants
(<
1
year
old),
children
1
6,
children
7
12,
females
13
50,
males
13
19,
males
20+,
and
seniors
55+.
The
results
for
the
other
population
subgroups
are
included
in
the
appendices.
They
are
not
included
in
the
tables
because
the
numbers
of
respondents
in
the
other
subgroups
were
not
sufficient;
and
therefore,
the
exposure
estimates
for
these
subgroups
contained
higher
levels
of
uncertainty.
However,
the
respondents
in
these
subgroups
were
also
part
of
larger
subgroups
which
are
listed
in
the
Tables.
For
example,
nursing
and
non
nursing
infants
are
included
in
all
infants.
[Hexazinone]
Dietary
Exposure
Assessment
DP
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PC
Code:
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Page:
6
of
9
Results
of
Acute
Dietary
Exposure
Analysis
Results
are
reported
at
the
95th
percentile
of
exposure
because
the
assessment
incorporated
100%
CT.
The
acute
dietary
risk
estimates
are
provided
for
the
population
subgroup
consisting
of
females
aged
13
through
50
years
only.
This
assessment
concludes
that
the
exposure
is
below
HED's
level
of
concern
for
this
subgroup.
Exposures
as
a
percentage
of
the
RfD
are
calculated
to
be
less
than
1%
at
the
95
th
percentile.
Table
2.
Results
of
Acute
Dietary
Exposure
Analysis
at
the
95
th
Percentile
of
Exposure
Population
Subgroup
aPAD
(mg/
kg/
day)
Exposure
(mg/
kg/
day)
%
aPAD
Females
13
50
years
old
4.
0
0.003611
<1
Results
of
Chronic
Dietary
Exposure
Analysis
Table
3.
Results
of
Chronic
Dietary
Exposure
Analysis
Population
Subgroup
cPAD
(mg/
kg/
day)
Exposure
(mg/
kg/
day)
%
cPAD
U.
S.
Population
(total)
0.
05
0.
002167
4
All
Infants
(<
1
year)
0.
05
0.
003752
7
Children
1
6
years
0.
05
0.
007449
15
Children
7
12
years
0.
05
0.
003964
8
Females
13
50
0.05
0.001308
3
Males
13
19
0.05
0.002334
5
Males
20+
years
0.
05
0.
001208
2
Seniors
55+
0.05
0.001159
2
The
chronic
dietary
risk
estimates
are
provided
for
the
U.
S.
population
(total)
and
various
population
subgroups.
This
assessment
concludes
that
the
exposure
is
below
HED's
level
of
concern
for
all
population
subgroups
examined.
Exposures,
as
a
percentage
of
the
RfD,
ranged
from
approximately
3%
for
females
aged
13
through
50
years
to
15%
for
children
aged
1
through
6
years.
[Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
7
of
9
VII.
Conclusions
The
Tier
1
acute
and
chronic
dietary
risk
assessments
were
conducted
for
all
supported
hexazinone
food
uses.
Dietary
risk
estimates
are
provided
for
the
U.
S.
population
(total)
and
various
population
subgroups.
This
assessment
concludes
that
for
all
supported
registered
commodities,
the
acute
risk
estimates
are
below
the
Agency's
level
of
concern
at
the
95
th
exposure
percentile
for
the
population
subgroup
consisting
of
females
aged
13
to
50
years.
The
acute
dietary
exposure
estimate
for
this
group
is
<1%
of
the
aPAD.
This
assessment
also
concludes
that
for
all
commodities,
the
chronic
risk
estimates
are
below
the
Agency's
level
of
concern
for
the
U.
S.
population
(total)
(4%
of
the
cPAD)
and
all
population
subgroups.
The
most
highly
exposed
population
subgroup
is
children
aged
1
to
6
years.
The
chronic
dietary
exposure
estimate
for
the
highest
exposed
population
subgroup
is
15%
of
the
cPAD.
[Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
8
of
9
Appendix
U.
S.
Environmental
Protection
Agency
Ver.
7.76
DEEM
Chronic
analysis
for
HEXAZINONE
(1989
92
data)
Residue
file
name:
C:\
WINDOWS\
Desktop\
hexazinone\
107201accr.
RS7
Adjustment
factor
#2
NOT
used.
Analysis
Date
07
31
2002/
14:
53:
38
Residue
file
dated:
07
31
2002/
14:
52:
49/
8
Reference
dose
(RfD,
Chronic)
=
.05
mg/
kg
bw/
day
===============================================================================
Total
exposure
by
population
subgroup
Total
Exposure
Population
mg/
kg
Percent
of
Subgroup
body
wt/
day
Rfd
U.
S.
Population
(total)
0.002167
4.3%
U.
S.
Population
(spring
season)
0.002199
4.4%
U.
S.
Population
(summer
season)
0.002113
4.2%
U.
S.
Population
(autumn
season)
0.002263
4.5%
U.
S.
Population
(winter
season)
0.002095
4.2%
Northeast
region
0.002137
4.3%
Midwest
region
0.002400
4.8%
Southern
region
0.001990
4.0%
Western
region
0.002215
4.4%
Hispanics
0.002339
4.7%
Non
hispanic
whites
0.002172
4.3%
Non
hispanic
blacks
0.001975
4.0%
Non
hisp/
non
white/
non
black
0.002334
4.7%
All
infants
(<
1
year)
0.003752
7.5%
Nursing
infants
0.001188
2.4%
Non
nursing
infants
0.004830
9.7%
Children
1
6
yrs
0.007449
14.9%
Children
7
12
yrs
0.003964
7.9%
Females
13
19
(not
preg
or
nursing)
0.001829
3.7%
Females
20+
(not
preg
or
nursing)
0.001143
2.3%
Females
13
50
yrs
0.001308
2.6%
Females
13+
(preg/
not
nursing)
0.001968
3.9%
Females
13+
(nursing)
0.002252
4.5%
Males
13
19
yrs
0.002335
4.7%
Males
20+
yrs
0.001208
2.4%
Seniors
55+
0.001160
2.3%
Pacific
Region
0.002206
4.4%
[Hexazinone]
Dietary
Exposure
Assessment
DP
Barcode:
[D279898]
PC
Code:
[107201]
Page:
9
of
9
Attachment
(electronic
file
id
107201accr.
rs7).
cc:
JSPunzi
(RRB2),
Hexazinone
Reg.
Std.
File,
Hexazinone
SF,
RF,
LAN.
7509C:
RRB2:
John
S.
Punzi:
CM2:
Rm
712M:
703
305
7727:
05/
15/
2002.
(Revised
07/
31/
02).
| epa | 2024-06-07T20:31:42.968064 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0025/content.txt"
} |
EPA-HQ-OPP-2002-0188-0026 | Supporting & Related Material | "2002-09-16T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
August
22,
2002
SUBJECT:
Response
to
DuPont's
Comments
Concerning
the
HED
Chapter
for
the
Hexazinone
Tolerance
Reassessment
Eligibility
Decision.
PC
Code
107201.
Case
0026.
DP
Barcode
D284193.
FROM:
Carol
Christensen,
MPH
Reregistration
Branch
II
Health
Effects
Division
(7509C)
THRU:
Al
Nielsen,
Branch
Senior
Scientist
Reregistration
Branch
II
Health
Effects
Division
(7509C)
TO:
Dirk
Helder,
Chemical
Review
Manager
Special
Review
and
Reregistration
Division
(7508C)
This
document
acknowledges
the
comments
received
from
the
registrant,
DuPont,
citing
errors
in
the
HED
Chapter
for
the
Hexazinone
Tolerance
Reassessment
Eligibility
Decision
(TRED)
and
related
materials.
The
Agency
has
provided
its
response
to
these
comments
herein.
The
comments
are
also
directly
reflected
in
the
Revised
HED
Chapter
for
the
Hexazinone
TRED
(D275621,
August
22,
2002)
and
accompanying
disciplinary
chapters
and
memoranda,
where
appropriate.
The
comments
consisted
primarily
of
editorial
suggestions,
an
objection
to
the
28
day
inhalation
study
requirement,
and
a
statement
that
because
the
Agency
has
received
a
new
developmental
toxicity
study
in
rabbits
the
10X
database
uncertainty
factor
previously
assigned
for
risk
assessment
be
removed.
Most
of
the
editorial
comments
have
been
included.
The
comment
objecting
to
the
28
day
inhalation
study
requirement
is
rejected.
The
new
developmental
toxicity
study
in
rabbits
is
acceptable
and
is
included
in
the
risk
assessment
and
the
database
uncertainty
factor
for
lack
of
a
developmental
toxicity
study
in
the
rabbit
is
removed.
Four
minor
comments
regarding
the
residue
chemistry
and
dietary
exposure
and
risk
assessment
are
also
reflected
in
the
documentation
for
the
hexazinone
TRED.
2
The
following
comments
were
received
from
DuPont
on
July
2
nd
,
2002.
The
comments
are
repeated
here
by
document
type
and
section
followed
by
the
Agency's
numbered
responses.
Toxicological
Chapter
for
the
TRED
for
Hexazinone
Section
2.0
REQUIREMENTS
C
Guideline
Numbers
need
to
be
filled
in
for
Structural
Chromosome
Aberrations
(870.
5375
and
870.5385)
and
Other
Genotoxic
Effects
(870.5550)
Agency
Response
1:
The
guideline
study
870.5385
is
unacceptable
and
will
not
be
listed
in
Table
1
(of
the
Toxicology
chapter).
The
guideline
study
870.5395
(an
acceptable
study)
will
listed
instead.
C
Although
not
listed
as
a
data
gap,
870.5100
"Gene
mutation
bacterial"
is
listed
as
a
requirement
that
is
not
satisfied.
DuPont
has
an
Ames
assay
for
the
75DF
formulation
that
was
conducted
for
another
country.
That
assay
was
conducted
in
both
Salmonella.
and
E.
Coli
at
up
to
5000
ug/
plate
(=
3750
ug/
plate
a.
i.)
and
was
negative
for
gene
mutations
in
both.
That
study
can
be
submitted,
if
needed,
to
satisfy
this
requirement.
Agency
Response
2:
The
new
study
in
Salmonella
and
E.
coli
(MRID#
457101001)
has
been
received
and
is
in
review,
however
no
data
gap
for
mutagenicity
was
determined
because
there
is
an
acceptable
in
vivo
mutation
study
and
there
is
insufficient
evidence
of
carcinogenicity
in
acceptable
studies.
Section
3.0
DATA
GAPS
C
It
is
unclear
as
to
why
a
28
day
inhalation
study
is
being
requested.
For
which
risk
assessment
is
it
needed?
There
are
no
residential
uses
of
hexazinone.
Most
of
the
use
patterns
are
outside
the
scope
of
WPS.
The
Agency
comments
on
page
24
of
the
HIARC
document,
that
it
already
has
an
unreviewed
21
day
inhalation
study
(MRID
#
00063972,
HLR
447
76).
In
that
study,
groups
of
ten
male
rats
were
exposed
6
hours/
day,
5
day/
week
for
3
weeks
to
0
(control)
or
2.5
mg/
L
of
90%
wettable
powder
formulation
of
hexazinone
(~
600
mg
a.
i./
kg/
day).
Histopathology
examination
indicated
that
lung
changes
were
similar
between
control
and
hexazinone
exposed
rats.
Intermittent
weight
losses
were
noted
throughout
the
test
period
but
all
rats
showed
a
normal
rate
of
weight
gain
during
the
recovery
period.
The
Registrant
acknowledges
that
this
is
an
old
study
which
was
conducted
prior
to
issuance
of
current
guidelines.
However,
it
indicates
that
repeated
exposure
to
hexazinone
dust
poses
negligible
inhalation
risks
and
that
no
further
inhalation
testing
should
be
required.
3
Agency
Response
3:
The
21
day
inhalation
study
(MRID#
00063972)
remains
an
unacceptable
study
(TXR
No.
0051033);
the
study
fails
to
meet
the
minimum
standard
for
review.
The
1976
study
is
unacceptable
because
it
is
a
two
page
summary
of
a
study,
with
no
meaningful
supporting
data.
In
addition,
there
is
considerable
doubt
about
the
particle
size
in
the
exposure
chamber.
A
particle
size
expressed
as
an
average
instead
of
a
mean
mass
areodynamic
diameter
is
not
meaningful.
Other
deficiencies
exist,
including:
(1)
failure
to
explain
dust
generator
type;
(2)
failure
to
note
the
sampling
area
with
respect
to
the
exposed
animal;
(3)
failure
to
supply
concentrations
of
various
mean
mass
areodynamic
diameters
of
various
particle
sizes;
(4)
inconsistency
in
expression
of
particle
sizes,
i.
e.,
average
of
7.8
µm(
2.3
15
µm)
and
a
note
indicating
that
only
0.06%
of
the
hexazinone
was
less
than
10.9
µm;
(5)
no
individual
body
weight
data
or
individual
pathology
data
was
submitted;
(6)
only
5
of
the
10
animals
were
subjected
to
gross
and
histological
examination;
(7)
the
study
was
not
conducted
under
GLPs,
which
would
at
least
confirm
that
the
opinions
expressed
may
have
supporting
data;
and,
(8)
the
particle
size
of
7.8
µm
(even
if
incorrectly
expressed
as
an
average)
is
not
sufficiently
small
to
test
the
inhalation
toxicity
of
hexazinone.
The
paucity
of
lung
macrophages
containing
dust
particles
supports
low
exposure
to
the
lung.
If
the
registrant
can
show
that
there
is
no
inhalation
exposure
to
handlers,
a
data
waiver
will
be
considered.
If
the
registrant
wishes
to
resubmit
the
21
day
inhalation
study
(MRID#
00063972)
with
the
missing
information
and
data,
OPP
will
review
it.
Until
this
information
is
reviewed
and
accepted,
the
21/
28
day
inhalation
study
is
required
for
confirmation.
A
new
Rabbit
Developmental
Toxicity
Study
has
recently
been
submitted.
(DuPONT
7405,
MRID
45677801).
Agency
Response
4:
The
recently
submitted
developmental
toxicity
study
in
rabbits
(MRID
42677801)
is
acceptable
and
will
be
included
in
the
risk
assessment
of
hexazinone
(TXR#
0050786).
The
acceptability
of
the
study
and
its
use
in
risk
assessment
are
reflected
throughout
the
HED
chapters
of
the
Hexazinone
TRED.
The
database
uncertainty
factor
(10x)
is
removed
from
the
assessment
of
risk
as
a
result
of
hexazinone
exposure.
Section
4.0
HAZARD
ASSESSMENT
Acute
Toxicity,
Page
5.
References:
The
references
for
all
the
acute
tox
citations
have
been
omitted
from
the
reference
list.
Should
they
be
included?
4
Agency
Response
5:
The
references
are
included.
Acute
Dermal
Rabbit,
add
date
(1973).
Agency
Response
6:
The
date
is
added.
Acute
Inhalation:
Is
not
correct
as
written
since
an
LC50>
3.94
mg/
L
(4
hour)
would
be
a
toxicity
category
IV.
Either
add
a
note
similar
to
that
used
in
the
HIARC
document
(Section
8)
that
this
was
on
a
25%
formulation
AND/
OR
cite
the
1973
study
on
the
technical
material
00104975
LC50>
7.5
mg/
L
(1
hour)
~
LC50
1.9
mg/
L
(4
hours)
that
was
mentioned
in
the
HIARC
report
Section
8.0.
Either
study
(3.94
x
0.25
or
7.5/
4)
would
result
in
a
toxicity
category
III.
Agency
Response
7:
Acute
inhalation
is
correct
as
written
and
will
not
be
changed.
The
acute
inhalation
study
used
to
support
the
data
requirements
was
changed
from
a
study
performed
in
1973
to
a
study
performed
in
1990.
The
acute
inhalation
study
performed
in
1990
(MRID#
41756701)
is
a
study
of
the
technical
grade
of
hexazinone
and
results
in
classification
as
an
acute
toxicity
category
III.
This
result
is
reflected
in
the
HED
Chapter
of
the
risk
assessment,
the
toxicology
chapter
and
all
HIARC
documents
(1/
16/
02,
4/
29/
02
and
8/
12/
02).
Subchronic
Toxicity,
870.3200,
Subchronic
Dermal,
Page
7.
Should
read
"
870.3200
21/
28
Day
Dermal
Toxicity
Rabbit"
since
the
guideline
is
for
either
rats
or
rabbits
and
the
study
was
conducted
in
rabbits.
Agency
Response
8:
The
guideline
toxicity
study
870.3200
listed
as
a
21/
28
day
dermal
toxicity
study
in
the
rat
will
be
changed
to
21/
28
day
dermal
toxicity
study
in
the
rabbit
since
the
study
was
conducted
in
this
species.
90
Day
Inhalation,
870.3465,
Page
8.
As
described
above,
the
registrant
does
not
agree
that
this
is
a
data
gap
because
the
Agency
has
an
unreviewed
21
day
repeated
dose
inhalation
study.
Agency
Response
9:
See
Agency
Response
3
(above).
Prenatal
Developmental,
870.3700b,
Toxicity
Study
Rabbit,
Page
10.
This
should
be
updated
to
reflect
that
a
new
rabbit
developmental
study
was
submitted
(5/
19/
02
MRID
45677801).
Agency
Response
10:
See
Agency
Response
4
(above).
4.7
Mutagenicity:
Overview.
For
clarification,
we
recommend
inserting
the
following
wording
into
the
last
sentence
of
the
mutagenicity
overview.
"Because
unambiguous
positive
results
were
achieved,
it
was
concluded
that
the
study
5
provided
adequate
evidence
that
INA
3674
112
(hexazinone
technical)
is
clastogenic
in
vitro
in
an
acceptable
study.
[However,
negative
results
were
obtained
in
two
studies
which
assessed
chromosome
damage
in
vivo."]
Agency
Response
11:
The
in
vivo
studies
for
chromosomal
damage
are
listed
as
negative.
There
is
no
reason
to
repeat
the
results
in
the
last
sentence
of
the
4.7
Mutagenicity
Overview
section
of
the
Toxicology
Chapter.
Page
20,
870.5375
Mid
paragraph
"In
the
presence
of
S
9
mix,
no
statistically
significant
increases
in
chromosome
aberrations
were
seen
in
Trial
1;
however,
very
low
positive
control
values
indicated
a
problem
with
the
S9
mix."
Delete
the
latter
part
of
the
sentence;
it
is
incorrect.
Positive
control
values
in
both
trials
produced
strong
positive
results
(Trial
1
28
32%
abnormal
cells,
Trial
2
36
40%
abnormal
cells).
Agency
Response
12:
The
statement
will
be
deleted
from
the
Toxicology
chapter.
Page
21,
870.5385
After,
"Unacceptable….
The
study
does
not
satisfy
the
requirement
for
FIFRA
Test
Guidelines."
Add,
"However
this
Guideline
is
fulfilled
by
an
acceptable
mouse
micronucleus
study."
Agency
Response
13:
Section
4.7.4
Guideline
870.5385:
In
vivo
cytogenics
assay
in
rat
bone
marrow
cells
will
not
be
changed.
The
mouse
micronucleus
test
is
listed
as
acceptable
in
Section
4.7.5
and
there
is
no
reason
to
repeat
the
results
in
Section
4.7.4.
Page
22,
870.5395
Change
the
last
sentence
from
"It
satisfy
the
requirements…."
to
"It
satisfies
the
requirements…."
Agency
Response
14:
The
correction
is
accepted.
Section
6.0
FQPA
CONSIDERATIONS
Page
25.
The
Agency
assigned
an
additional
10x
database
uncertainty
factor
(UFdb)
because
a
rabbit
developmental
study
was
unacceptable
due
to
uncertainties
in
the
LOEL.
Immediately
after
the
HIARC
report
issued,
the
Registrant
submitted
a
new
rabbit
developmental
study
(DuPont
7405,
MRID
45677801)
to
the
Agency.
The
new
rabbit
developmental
study
was
conducted
using
current
guidelines
and
confirmed
the
results
of
the
previous
rabbit
developmental
study.
The
maternal
and
fetal
rabbit
NOAEL
was
50
mg/
kg/
day.
The
maternal
and
fetal
LOAEL
was
125
mg/
kg/
day.
Once
the
new
rabbit
study
is
reviewed,
if
it
is
selected
as
the
basis
of
the
ARfD,
the
registrant
believes
the
extra
10x
UFdb
should
be
removed.
6
Agency
Response
15:
See
Agency
Response
4.
Acute
Toxicity
Table.
Header
should
read:
"Acute
Toxicity
Data
on
HEXAZINONE"
NOT
"Acute
Toxicity
Data
on
FENBUTATIN
OXIDE."
Agency
Response
16:
The
heading
for
the
table
"Acute
Toxicity
Data
on
FENBUTATIN
OXIDE"
will
be
changed
to
"Acute
Toxicity
Data
on
HEXAZINONE."
Subchronic,
Chronic,
and
Other
Toxicity
Tables.
Registrant
comments
have
been
made
above
regarding
removal
of
the
28
day
inhalation
study
requirement,
the
submission/
MRID
of
a
new
prenatal
developmental
study,
and
the
availability
of
an
unsubmitted
gene
mutation
assay
(with
a
75DF
formulation)
in
Salmonella
and
E.
Coli.
Agency
Response
17:
See
Agency
Responses
3,
4,
and
2,
respectively.
Summary
of
Toxicological
Endpoints.
Registrant
restates
that
additional
10x
UFdb
should
be
removed
after
new
rabbit
developmental
toxicity
study
is
reviewed
and
questions
the
need
for
establishment
of
long
term
occupational
endpoints.
Agency
Response
18:
See
Agency
Response
4.
The
Long
Term
endpoints
were
selected
for
completeness
and
for
potential
future
need.
7
Hazard
Identification
and
Review
Committee
(HIARC)
Report
Acute
Dietary
Reference
Dose
Females
13
50
pp.
3
5.
For
setting
the
acute
reference
dose
(ARfD)
for
females
of
childbearing
age,
the
Agency
has
selected
a
rat
developmental
study
with
NOAELs
of
100
and
400
mg/
kg
for
maternal
and
fetal
effects,
respectively.
The
Agency
assigned
an
additional
10x
database
uncertainty
factor
(UFdb
)
because
a
rabbit
developmental
study
was
unacceptable
due
to
uncertainties
in
the
LOEL.
A
UFdb
factor
of
10x
rather
than
3x
was
used
because,
based
on
extrapolation
to
the
rabbit
pilot
NOEL
of
50
mg/
kg
in
the
previous
study,
it
was
concluded
the
difference
between
rabbits
and
rats
may
be
greater
than
3x.
The
resulting
ARfD
was
0.4
mg/
kg
(400
mg/
kg
/
1000).
Immediately
after
the
HIARC
report
issued,
the
Registrant
submitted
a
new
rabbit
developmental
study
(DuPont
7405,
MRID
45677801)
to
the
Agency.
The
new
rabbit
developmental
study
was
conducted
using
current
guidelines
and
confirmed
the
results
of
the
previous
rabbit
developmental
study.
The
maternal
and
fetal
rabbit
NOEL
was
50
mg/
kg/
day.
The
maternal
and
fetal
LOEL
was
125
mg/
kg/
day
based
on
weight
effects,
which
were
only
slight
in
the
fetus.
A
higher
dose,
175
mg/
kg/
day
produced
severe
maternal
toxicity.
Once
the
new
rabbit
study
is
reviewed,
if
it
is
selected
as
the
basis
of
the
ARfD,
the
registrant
believes
the
extra
10x
UFdb
should
be
removed.
If
selected,
this
would
result
in
an
ARfD
of
0.5
mg/
kg
(50
mg/
kg
/
100).
This
is
essential
the
same
(slight
improvement)
as
the
current
ARfD,
and
thus
there
will
be
essentially
no
change
in
the
acute
dietary
risk
assessment.
Agency
Response
19:
The
rabbit
developmental
toxicity
study
has
been
reviewed
and
accepted
by
the
Agency.
The
database
uncertainty
factor
of
10X
is
removed
from
the
acute
dietary
risk
assessment.
However,
the
Agency
retains
the
use
of
the
developmental
toxicity
study
in
the
rat
as
the
basis
for
the
acute
reference
dose
for
females
13
50
years
of
age
(acute
reference
dose
is
4.0
mg/
kg/
day).
Chronic
Reference
Dose,
Last
line
page
6
–
typographical
error.
"The
LOAEL
is…
based
on…[
findings
listed]
and
clinical
observations
of
thinnest
in
one
male."
Should
read
"thin
appearance
in
one
male."
Agency
Response
20:
The
statement
is
changed
to
read
"thinness
in
one
male"
(p.
12
of
HIARC
report
TXR
No.
0051033
dated
August
12,
2002).
Occupational/
Residential
Exposure.
It
is
not
clear
to
the
Registrant
why
the
occupational
and
residential
exposure
Sections
2.4.1
through
2.6
were
included
in
a
food
Tolerance
Reassessment.
There
are
no
residential
uses
of
hexazinone,
that
could
contribute
to
the
aggregate
exposure.
It
is
the
Registrant's
understanding
that
occupational
exposure
assessment
is
beyond
the
scope
of
Tolerance
Reassessment.
8
Occupational
exposure
was
addressed
under
the
1994
Reregistration
Eligibility
Document.
It
was
noted
that
a
number
of
the
major
uses
of
hexazinone
were
outside
the
scope
of
the
Worker
Protection
Standard
(WPS).
While
agricultural
uses
and
use
on
sod
farms
was
within
WPS;
use
on
pastures,
rangeland,
plants
grown
for
other
than
commercial
purposes,
ornamental
plants
in
parks
and
golf
course,
and
no
agricultural
uses
such
as
vegetation
along
rights
of
way
were
outside
of
the
scope
of
WPS.
No
worker
exposure
assessment
was
conducted.
Therefore
the
Registrant
considers
the
selection
of
Occupational/
Residential
endpoints
(e.
g.,
dermal
and
inhalation
exposure
scenarios)
to
not
be
relevant
to
Tolerance
Reassessment.
Nonetheless,
we
offer
the
following
comments
to
the
endpoint
selection,
should
these
endpoints
be
considered
relevant
in
the
future.
Agency
Response
21:
These
comments
will
not
be
addressed
as
occupational
and
residential
exposure
as
risk
assessment
was
not
performed
for
the
HED
Chapter
of
the
Hexazinone
TRED.
These
endpoints
were
selected
for
completeness
of
the
toxicological
database
and
for
potential
future
need.
Dermal
Absorption.
The
review
states
that
"No
dermal
absorption
study
is
available."
It
would
be
clearer
to
say
that
"No
dermal
penetration
study
is
available.
For
an
estimate
of
dermal
penetration,
the
NOAEL
from
the
21
day
rabbit
dermal
toxicity
study…."
Also,
for
clarification,
add
the
MRID
of
the
rabbit
21
day
study
(MRID
41309005).
The
Agency
extrapolated
a
dermal
absorption
factor
by
comparing
the
NOAEL
in
a
21
day
dermal
study
in
rabbits
to
the
LOAEL
from
a
rabbit
developmental
rangefinding
study.
A
25%
dermal
absorption
factor
was
derived.
Rabbit
Pilot
Developmental
LOAEL
(oral)
=
250
mg/
kg
=
25%
Rabbit
21
Day
Dermal
NOAEL
1000
mg/
kg
However,
the
new
rabbit
developmental
study
(DuPont
7405,
MRID
45677801)
indicates
there
is
a
greater
difference
between
oral
and
dermal
toxicity
than
indicated
by
the
above
calculation.
Further,
since
no
LOAEL
was
actually
established
on
the
Rabbit
21
Day
Dermal
study,
use
of
a
dermal
NOAEL
in
comparison
to
an
oral
LOAEL,
overestimates
the
potential
dermal
penetration.
Based
on
the
new
rabbit
developmental
study,
dermal
absorption
is
no
greater
than
12.5%
Rabbit
Developmental
LOAEL
(oral)
=
125
mg/
kg
=<
12.5%
Rabbit
21
Day
Dermal
NOAEL
>
1000
mg/
kg
9
Agency
Response
22:
A
dermal
absorption
factor
of
12.5%
is
defined
in
the
recent
HIARC
report.
(TXR
No.
0051033
dated
August
12,
2002)
Short
Term
(1
Day
–
1
Month)
Dermal
Exposure
and
Intermediate
Term
(1
6
Months)
and
Long
Term
(>
6
Months)
Dermal
Exposures.
Under
2.4.3,
the
Agency
states
the
Dose
and
Endpoint
for
Risk
Assessment
for
short
term
dermal
Exposure
is
Not
Applicable
and
that
No
Hazard
and
No
Quantification
are
required
(based
on
no
effects
in
the
21
day
dermal
study
in
rabbits).
However,
in
the
next
section
(2.4.4)
the
Agency
proceeds
to
select
longer
term
dermal
endpoints
based
on
the
chronic
dog
study
NOEL
(5
mg/
kg/
day)
and
a
25%
dermal
absorption
factor
(i.
e.
equivalent
to
20
mg/
kg/
day).
For
intermediate
term
scenarios,
we
believe
selection
of
a
subchronic
endpoint
would
be
more
appropriate
than
selection
of
the
chronic
dog
study
with
a
25%
absorption
factor.
It
is
also
consistent
wit
the
Agency
guidance
document,
Toxicology
Endpoint
Selection
Process
(February,
1997).
Based
on
the
labeled
uses
for
hexazinone,
we
do
not
believe
a
long
term
dermal
exposure
scenario
is
relevant.
It
is
difficult
to
identify
a
scenario
where
there
would
be
daily,
lifetime
uninterupted
dermal
exposure
to
hexazinone.
The
registrant
believes
that
the
route
specific
rabbit
dermal
study
is
the
most
appropriate
study
to
estimate
subchronic
human
dermal
exposure.
The
Agency
has
concluded
that
the
repeated
dose
rabbit
study
(MRID
41309005)
meets
guidelines
and
is
acceptable.
It
measured
the
proper
endpoints
to
identify
hexazinone
toxicity
(including
body
weights,
clinical
chemistry,
liver
histology).
Considering
lifespan
differences,
it
is
of
appropriate
duration
for
short
term
and
intermediate
endpoint
selection.
However,
if
the
Agency
deems
that
the
duration
of
the
subchronic
rabbit
dermal
study
is
insufficient,
acceptable
subchronic
oral
studies
of
longer
duration
(90
days)
are
available.
The
NOAELs
from
the
rat
and
dog
90
day
studies
were
84
and
29
mg/
kg,
respectively.
Again
the
dog
is
the
most
sensitive
species,
but
the
subchronic
NOAEL
is
more
appropriate.
As
noted
in
the
discussion
above,
the
25%
absorption
factor
derived
by
comparing
a
LOAEL
on
a
rabbit
pilot
developmental
study
to
the
NOAEL
on
the
rabbit
subchronic
dermal
study
overestimated
the
Dermal
Absorption
Factor
which,
in
reality,
is
likely
to
be
less
than
12.5%.
Using
the
dog
subchronic
NOAEL
(29
mg/
kg/
day)
and
applying
a
more
appropriate
dermal
absorption
factor
<12.5%
would
result
in
an
estimated
dermal
endpoint
of
>
232
mg/
kg/
day.
This
is
much
more
comparable
to
the
actual
dermal
NOAEL
determined
from
the
21
day
rabbit
study.
10
Also
typographical
error
in
2.4.4
"thinnest
in
one
males"
should
read
"thin
appearance
in
one
male"
Agency
Response
23:
The
Agency's
rationale
for
endpoint
selection
are
included
in
the
updated
HIARC
document
(TXR
No.
0051033
dated
August
12,
2002)
and
the
Agency
will
not
comment
further
at
this
time.
See
Agency
Response
22
concerning
the
dermal
absorption
factor.
Intermediate
(1
6
Months)
and
Long
Term
(>
6
Months)
Inhalation
Exposure
Typographical
error
"thinnest
in
one
males"
should
read
"thin
appearance
in
one
male."
Agency
Response
24:
This
error
is
noted
and
will
be
changed
in
the
Toxicology
chapter.
Section
4.0
Mutagenicity
For
clarification,
we
recommend
inserting
the
following
wording
into
the
last
sentence
of
the
mutagenicity
overview
(additions
are
in
bold).
"Because
unambiguous
positive
results
were
achieved,
it
was
concluded
that
the
study
provided
adequate
evidence
that
INA
3674
112
(hexazinone
technical)
is
clastogenic
in
vitro
in
an
acceptable
study.
However,
negative
results
were
obtained
in
two
studies
which
assessed
chromosome
damage
in
vivo."
General
Comment:
for
consistency
with
the
rest
of
the
document,
INA
3674
112
should
be
changed
to
hexazinone
or
hexazinone
technical.
Agency
Response
25:
See
Agency
Response
11.
Guideline
870.5300:
Gene
Mutation
Assay
in
Mammalian
Cells.
Conclusion
should
be
bolded
as
with
others
studies.
"There
was,
however,
no
indication
that
INA
3674
112
induced
mutagenic
effect
in
either
the
presence
or
the
absence
of
S9
activation."
Agency
Response
26:
The
comment
is
accepted
as
suggested
by
the
registrant.
(Section
4.2,
p.
21
of
the
3
rd
Report
of
the
HIARC,
TXR
No.
0051033
dated
August
12,
2002.)
Guideline
870.5395:
Mouse
Bone
Marrow
Micronucleus
Assay.
Change
the
last
sentence
from
"It
satisfy
the
requirements…."
to
"It
satisfies
the
requirements…."
Agency
Response
27:
See
Agency
Response
14.
Guideline
870.5375:
Structural
Chromosome
Aberration
Assay;
In
vitro
Cytogenetic
Assay.
Mid
paragraph
"In
the
presence
of
S
9
mix,
no
statistically
11
significant
increases
in
chromosome
aberrations
were
seen
in
Trial
1;
however,
very
low
positive
control
values
indicated
a
problem
with
the
S9
mix."
Delete
the
latter
part
of
the
sentence;
it
is
incorrect.
Positive
control
values
in
both
trials
produced
strong
positive
results
(Trial
1
28
32%
abnormal
cells,
Trial
2
36
40%
abnormal
cells).
Agency
Response
28:
See
Agency
Response
12.
Guideline
870.5385:
Structural
Chromosome
Aberration
Assay;
In
vivo
Cytogenetic
Assay.
Fourth
sentence
of
second
paragraph,
"Few
or
no
analyzable
cell
were
available…"
should
be
"Few
or
no
analyzable
cells
were
available…"
Agency
Response
29:
Editorial
comment
will
be
made.
Section
4.5,
Guideline
870.5395:
After,
"Unacceptable….
The
study
does
not
satisfy
the
requirement
for
FIFRA
Test
Guidelines."
add,
"However,
this
Guideline
is
fulfilled
by
an
acceptable
mouse
micronucleus
study."
Agency
Response
30:
See
Agency
Response
13.
Section
5
FQPA
Considerations
Developmental
Toxicity,
Developmental
Toxicity
in
the
Rabbit.
Last
paragraph
should
be
upgraded
to
indicate
a
Rabbit
Developmental
Toxicity
(45677801)
has
just
been
submitted
but
not
yet
been
reviewed.
Agency
Response
31:
See
Agency
Response
4.
The
receipt
and
acceptance
of
the
developmental
toxicity
study
in
the
rabbit
is
reflected
throughout
the
HED
risk
assessment
documents,
including
the
revised
HIARC
report
(TXR
No.
0051033
dated
August
12,
2002.)
Determination
of
the
Need
for
Developmental
Neurotoxicity
Study,
Evidence
that
suggest
requiring
a
Developmental
Neurotoxicity
Study.
Atrazine
should
not
be
considered
as
evidence
suggesting
requirement
of
a
developmental
neurotoxicity.
Although
atrazine
and
hexazinone
contain
a
triazine
ring,
there
are
significant
structural
differences
that
contribute
substantial
differences
in
the
biological
response
to
these
molecules
by
laboratory
animals.
EPA
reached
a
similar
conclusion
in
the
Toxicology
Disciplinary
Chapter
for
the
Tolerance
Reassessment
and
Evaluation
Decision
Document,
Section
1.0
–
Hazard
Characterization
(May
16,
2002).
The
critical
structural
differences
include
substitutions
of
a
cyclohexyl
and
a
methyl
group
on
the
ring
nitrogens
and
the
presence
of
two
ring
oxo
groups
in
hexazinone.
As
a
result,
hexazinone
is
less
aromatic
in
character
than
the
chloro
s
triazines.
Collectively,
these
structural
differences
are
considered
to
contribute
differences
in
toxicological
properties.
Hexazinone
has
been
classified
12
as
a
triazine
dione
by
EPA,
which
further
indicates
this
Agency
acknowledges
its
differences
from
the
chloro
s
triazine
herbicide
class.
Hexazinone
has
been
extensively
tested
for
safety
to
mammals.
A
key
difference
between
hexazinone
and
atrazine
and
other
members
of
the
chloro
s
triazine
class
is
that
chronic
exposures
to
the
latter
produce
a
characteristic
mammary
tumor
response
in
Sprague
Dawley
rats.
The
mode
of
action
for
this
chloro
s
triazine
induced
tumor
response
has
been
associated
with
altered
endocrine
activity
unique
to
this
rat
strain.
In
contrast
hexazinone
does
not
induce
rat
mammary
tumors,
which
indicates
the
absence
of
the
endocrine
modulation
responsible
for
this
effect.
Additional
evidence
supporting
the
absence
of
endocrine
effects
with
hexazinone
includes
the
absence
of
endocrine
organ
effects
and
effects
on
reproduction
and
development.
The
differences
in
chemical
structures
are
considered
to
be
critical
to
the
observed
differences
in
toxicological
response
between
hexazinone
and
the
chloro
s
triazines.
Agency
Response
32:
As
stated
in
the
HED
Chapter
of
the
hexazinone
risk
assessment,
there
was
no
evidence
of
endocrine
disruption
in
the
hexazinone
toxicological
database.
However,
when
appropriate
screening
and/
or
testing
protocols
have
been
developed
through
the
Endocrine
Disruptor
Screening
Program
(EDSP)
hexazinone
may
be
subject
to
additional
screening
and/
or
testing
to
further
characterize
effects
related
to
endocrine
disruption.
Section
7.0
Data
Gaps
"HIARC
has
requested
a
28
day
inhalation
study
because
of
the
concern
for
inhalation
exposure
based
on
the
use
pattern"
It
is
unclear
as
to
which
use
pattern
is
being
considered.
There
are
no
residential
uses
of
hexazinone.
Most
of
the
use
patterns
are
outside
the
scope
of
WPS.
Since
no
use
patterns
of
concern
are
identified,
it
is
impossible
to
determine
duration
of
exposure.
On
the
same
page
that
it
requests
a
28
day
inhalation
study,
the
Agency
notes
that
it
already
has
an
unreviewed
21
day
inhalation
study
(MRID
#
00063972,
HLR
447
76).
In
that
study,
groups
of
ten
male
rats
were
exposed
6
hours/
day,
5
day/
week
for
3
weeks
to
0
(control)
or
2.5
mg/
L
of
90%
wettable
powder
formulation
of
hexazinone.
Using
the
guidance
in
(Whalan
EPA,
1997)
this
represents
an
exposure
of
greater
than
600
mg/
kg/
day
(2.25
mg
hexazinone
a.
i./
L
x
11.38
L/
hr
respiration
x
6
hr/
day
exposure/
0.25
kg
body
weight
).
Histopathology
examination
indicated
that
lung
changes
were
similar
between
control
and
hexazinone
exposed
rats.
Intermittent
weight
losses
were
noted
throughout
the
test
period
but
all
rats
showed
a
normal
rate
of
weight
gain
during
the
recovery
period
.
13
The
Registrant
acknowledges
that
this
is
an
old
study
which
was
conducted
prior
to
issuance
of
current
guidelines.
However,
it
clearly
indicates
that
repeated
exposure
to
hexazinone
dust
poses
negligible
inhalation
risk.
It
also
suggests
that
no
further
inhalation
testing
is
required
since
no
lung
toxicity
was
identified
and
since
the
exposure
producing
minimal
to
moderate
toxicity
was
two
orders
of
magnitude
higher
than
the
chronic
NOAEL
that
has
just
been
selected
by
the
Agency
to
set
an
inhalation
endpoint.
Therefore
the
oral
endpoint
selected
is
overly
protective.
In
the
interest
of
conservation
of
animals
we
strongly
urge
that
available
information
be
considered
before
the
Agency
request
another
study
and
the
repeated
dose
inhalation
be
removed
as
a
data
gap.
Agency
Response
33:
See
Agency
Response
3
(above).
For
the
rabbit
developmental
toxicity
data
gap
we
recommend
changing
the
statement
"is
expected
to
be
submitted"
to
"was
not
submitted
in
enough
time
for
review
prior
to
issuance
of
this
document"
Agency
Response
34:
This
statement
has
been
removed
from
the
most
recent
HIARC
report
(August
12,
2002,
TXR
0051033)
and
the
receipt
and
acceptance
of
the
developmental
toxicity
study
in
the
rabbit
is
reflected
appropriately
in
all
supporting
documentation
to
the
HED
risk
assessment.
14
HED
Chapter
of
the
Hexazinone
TRED
Section
1.0
Executive
Summary
The
most
significant
recommendation,
in
our
view,
contained
in
the
draft
documents
pertains
to
the
revocation
of
tolerances
and
associated
use
of
hexazinone
on
grass.
We
acknowledge
that
guidelines
and
interpretations
regarding
the
practicality
of
grower
control
over
cattle
grazing
intervals
have
changed
since
data
supporting
this
use
pattern
were
last
submitted.
However,
as
indicated
in
your
review,
this
is
a
rather
minor
use
and
our
information
indicates
that
the
current
label
restrictions
regarding
cutting
and
grazing
are
being
complied
with.
Therefore,
the
tolerances
supporting
the
use
are
sufficient.
Given
the
above,
we
request
that
the
existing
tolerances
and
use
pattern
be
maintained
while
we
conduct
new
residue
work
to
support
EPA's
interpretation
regarding
a
zero
day
grazing
interval.
Agency
Response
35:
The
Agency
cannot
reassess
the
tolerances
for
pasture
and
rangeland
grasses
without
these
data.
These
data
remain
outstanding
for
hexazinone
and
must
be
fulfilled
before
tolerance
reassessment
can
be
completed.
Therefore,
no
changes
are
made
to
the
Executive
Summary
concerning
this
issue.
We
understand
that
our
recently
submitted
Rabbit
Developmental
Toxicity
Study
(DuPont
7405,
MRID
45677801)
was
not
reviewed
in
time
to
be
included
in
the
Draft
TRED.
In
view
of
the
pivotal
importance
of
this
study
to
the
overall
conclusions
of
the
final
TRED
(specifically,
the
current
proposal
to
declare
a
significant
gap
in
the
toxicology
data
base,
the
selection
of
appropriate
end
points
for
regulatory
purposes
and
the
imposition
of
an
additional
10X
safety
factor
due
to
an
incomplete
data
base),
we
respectfully
request
that
this
study
be
reviewed
as
quickly
as
possible
to
be
included
in
the
final
TRED.
Agency
Response
36:
See
Agency
Response
4
(above).
We
also
note
in
the
toxicology
review
that
"Gene
mutation
–
bacterial"
is
listed
as
an
unsatisfied
requirement.
We
have
recently
submitted
(June
28,
2002,
no
MRID
yet
assigned)
a
new
Ames
assay
with
the
75
DF
formulation
which
we
believe
will
satisfy
this
requirement.
Agency
Response
37:
See
Agency
Response
2
(above).
Finally,
we
do
not
believe
a
28
day
inhalation
study
should
be
required
until
the
existing
and
submitted
21
day
inhalation
study
(MRID
00063972)
has
been
reviewed.
15
Agency
Response
38:
See
Agency
Response
3
(above).
Section
3.0
Hazard
Characterization
Hazard
Profile.
Table
1:
Acute
Toxicity:
For
Inhalation
LC50>
3.94
mg/
L
(4
hour),
add
(25%
formulation).
Agency
Response
39:
See
Agency
Response
7
(above).
Table
2:
Toxicity
Profile.
870.3465,
"A
28
day
inhalation
study
is
required."
As
noted
in
the
HIARC
document,
an
unreviewed
21
day
inhalation
study
is
available
(MRID
00063972)
which
indicates
that
repeated
exposure
to
hexazinone
dust
poses
negligible
inhalation
risks
and
that
no
further
inhalation
testing
should
be
required.
The
Registrant
requests
that
existing
data
be
reviewed
before
additional
testing
is
required.
Agency
Response
40:
See
Agency
Response
3
(above).
No
change
is
made
in
response
to
this
comment.
870.3700b
Prenatal
Developmental
Toxicity.
Unacceptable/
Upgradeable.
The
registrant
has
submitted
a
new
rabbit
developmental
study
(DuPONT
7405,
MRID
45677801)
which
addressed
the
deficiencies
and
supports
the
conclusions
of
the
original
study
Agency
Response
41:
See
Agency
Response
4
(above).
This
study
is
acceptable
and
appropriately
listed
in
the
Toxicological
Profile
Table
2
in
the
HED
Chapter
of
the
Hexazinone
Risk
Assessment.
870.5100
Reverse
mutation
in
Samonella
Strains.
Unacceptable:
DuPont
has
conduct
a
Ames
assay
for
the
75DF
formulation
in
both
Salmonella
and
E.
Coli
at
up
to
5000
ug/
plate
(=
3750
ug/
plate
a.
i.)
that
can
be
submitted,
if
needed,
to
satisfy
this
requirement.
The
results
were
negative
for
gene
mutations
in
both
species.
Agency
Response
42:
See
Agency
Response
2
(above).
870.5385
In
vivo
Rat
Bone
Marrow
Cytogenetics
Assay.
Unacceptable.
Add,
"However
this
Guideline
is
fulfilled
by
an
acceptable
mouse
micronucleus
study."
Agency
Response
43:
See
Agency
Response
13
(above).
FQPA
Considerations
and
Dose
Response
Assessment:
Acute
Reference
Dose
Females
13
50.
The
Agency
assigned
an
additional
10x
database
uncertainty
factor
because
a
rabbit
developmental
study
was
unacceptable
due
to
uncertainties
in
the
LOEL.
A
new
rabbit
developmental
study
(DuPont
7405,
MRID
16
45677801)
to
the
Agency
which
addresses
the
deficiencies
and
supports
the
previous
study.
Once
the
new
rabbit
study
is
reviewed,
the
registrant
believes
the
extra
10x
uncertainty
factor
should
be
removed.
Agency
Response
44:
See
Agency
Response
4
(above).
Acute
Aggregate
Risk
Assessment.
The
headings
for
the
last
three
columns
for
Table
11
(page
42)
should
specify
µg/
l
rather
than
g/
l.
Agency
Response
45:
The
headings
are
written
as
µg/
l
in
Table
11.
17
Report
of
the
FQPA
Safety
Factor
Committee
3.
Degree
of
Concern
and
Residual
Uncertainties.
For
setting
the
acute
reference
dose
(ARfD)
for
females
of
childbearing
age,
the
Agency
assigned
an
additional
10x
database
uncertainty
factor
(UFdb
)
because
a
rabbit
developmental
study
was
unacceptable
due
to
uncertainties
in
the
LOEL.
A
UFdb
factor
of
10x
rather
than
3x
was
used
because,
based
on
extrapolation
to
the
rabbit
pilot
NOEL
of
50
mg/
kg
in
the
previous
study,
it
was
concluded
the
difference
between
rabbits
and
rats
may
be
greater
than
3x.
Immediately
after
the
HIARC
report
issued,
the
Registrant
submitted
a
new
rabbit
developmental
study
(DuPont
7405,
MRID
45677801)
to
the
Agency.
The
new
rabbit
developmental
study
was
conducted
using
current
guidelines
and
confirmed
the
results
of
the
previous
rabbit
developmental
study.
The
maternal
and
fetal
rabbit
NOAEL
was
50
mg/
kg/
day.
The
maternal
and
fetal
LOAEL
was
125
mg/
kg/
day
based
on
weight
effects,
which
were
only
slight
in
the
fetus.
A
higher
dose,
175
mg/
kg/
day
produced
severe
maternal
toxicity.
Once
the
new
rabbit
study
is
reviewed,
if
it
is
selected
as
the
basis
of
the
ARfD,
the
registrant
believes
the
extra
10x
UFdb
should
be
removed.
Agency
Response
46:
See
Agency
Response
4
(above).
The
receipt
and
acceptance
of
the
developmental
toxicity
study
in
the
rabbit
is
also
reflected
in
report
Hexazinone
2
nd
Report
of
the
FQPA
Safety
Factor
Committee
(TXR
No.
0051049
dated
August
8,
2002.)
18
Dietary
Risk
Assessment
An
acute
endpoint
is
only
given
for
females
13
50.
We
assume
this
group
is
considered
by
EPA
to
be
the
most
sensitive
sub
population.
Agency
Response
47:
The
toxic
endpoint
with
which
acute
dietary
exposure
is
assessed
is
a
decrease
in
male
and
female
fetal
body
weight
and
increased
incidence
of
malformations
and
variations
of
the
fetus.
Because
the
toxic
endpoint
for
acute
dietary
exposure
concerns
in
utero
exposure,
the
risk
assessment
is
performed
for
females
of
childbearing
age
(females
13
50)
since
only
members
of
this
group
are
at
risk
of
being
pregnant
at
the
time
of
exposure.
In
several
places
we
note
the
risk
assessment
is
based
on
the
reassessed
tolerances
for
blueberry,
pineapple,
and
sugarcane.
For
blueberries
and
pineapple
0.3
ppm
is
utilized,
presumably
one
half
of
the
new
proposed
tolerance
of
0.6
ppm.
However,
for
sugarcane
0.6
ppm
(tolerance)
is
utilized.
This
appears
to
be
an
inconsistency.
Stated
differently,
it
is
not
clear
to
us
why
0.3
ppm
was
selected
for
blueberry
and
pineapple
while
0.6
ppm
was
selected
for
sugarcane.
Agency
Response
48:
This
was
an
error
and
has
been
corrected
in
the
documents
prepared
for
Phase
III
of
the
public
participation
process.
Residue
estimates
for
blueberry
and
pineapple
are
0.6
ppm.
(See
Revised
Acute
and
Chronic
Dietary
Exposure
Assessment
for
the
Hexazinone
TRED,
July
30,
2002.)
Clarity
is
needed
around
the
definition
of
LOQ.
There
are
both
enforcement
methods
(sum
of
LOQs
is
0.55
ppm)
and
data
collection
methods
(sum
of
LOQs
is
0.3
ppm).
We
recommend
that
the
enforcement
LOQs
be
used
consistently
throughout
the
document.
Agency
Response
49:
The
LOQ's
for
the
enforcement
method
is
used
for
dietary
exposure
estimates.
We
note
that
a
more
up
to
date
consumption
database
exists,
CSFII
94
96/
98.
Why
was
the
older
database,
CSFII
89
92,
used?
Agency
Response
50:
At
this
time,
it
is
Agency
policy
to
use
the
CSFII
1988
1992
food
consumption
database
to
perform
dietary
exposure
and
risk
assessment.
| epa | 2024-06-07T20:31:42.974160 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0026/content.txt"
} |
EPA-HQ-OPP-2002-0188-0027 | Supporting & Related Material | "2002-09-16T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
MEMORANDUM
DATE:
August
22,
2002
SUBJECT:
REVISED:
HED
Chapter
for
the
Hexazinone
Tolerance
Reassessment
Eligibility
Decision
PC
Code
107201.
Case
0266.
DP
Barcode
D275621.
FROM:
Carol
Christensen,
MPH
Reregistration
Branch
II
Health
Effects
Division
(7509C)
THRU:
Al
Nielsen,
Branch
Senior
Scientist
Reregistration
Branch
II
Health
Effects
Division
(7509C)
TO:
Dirk
Helder
Chemical
Review
Manager
Special
Review
and
Reregistration
Division
(7508C)
The
following
human
health
risk
assessment
has
been
prepared
by
the
Health
Effects
Division
(HED)
for
the
Phase
III
Public
Comment
Period
of
the
tolerance
reassessment
process
for
hexazinone
[3
cyclohexyl
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione].
The
HED
chapter
reflects
the
Agency's
current
guidelines
concerning
the
retention
of
the
Food
Quality
Protection
Act
(FQPA)
safety
factor
and
risk
assessment.
The
chapter
is
based
upon
the
product
chemistry
review
by
Ken
Dockter,
the
toxicology
review
by
David
Anderson,
the
residue
chemistry
and
dietary
exposure
and
risk
analysis
by
John
Punzi,
the
drinking
water
exposure
assessment
by
Larry
Liu
of
the
Environmental
Fate
and
Effects
Division
(EFED),
and
the
incident
review
by
Jerry
Blondell
and
Monica
Spann.
Table
of
Contents
1.0
Executive
Summary
.........................................................
3
2.0
Physical
and
Chemical
Properties
..............................................
5
3.0
Hazard
Characterization
......................................................
7
3.1
Hazard
Profile
.......................................................
7
3.2
FQPA
Considerations
................................................
16
3.3
Dose
Response
Assessment
............................................
16
3.3.1
Acute
Reference
Dose
(RfD)
Females
13
50
......................
17
3.3.2
Chronic
Reference
Dose
(RfD)
..................................
18
3.4
Endocrine
Disruption
.................................................
19
4.0
Exposure
Assessment
and
Characterization
.....................................
20
4.1
Summary
of
Registered
Use
Patterns
....................................
20
4.2
Dietary
(Food)
Exposure/
Risk
Pathway
..................................
21
4.2.1
Residue
Profile
.............................................
21
4.2.2
Acute
Dietary
Exposure
(Females
13
50)
..........................
28
4.2.3
Chronic
Dietary
..............................................
29
4.3
Water
Exposure/
Risk
Pathway
.........................................
31
4.3.1
Environmental
Fate
...........................................
33
4.3.2
Drinking
Water
Exposure
Estimates
..............................
34
4.4
Residential
Exposure/
Risk
Pathway
.....................................
38
4.4.1
Other
Non
Occupational
Exposures
..............................
38
5.0
Aggregate
Risk
Assessment
and
Characterization
................................
39
5.1
Acute
Aggregate
Risk
Assessment
......................................
40
5.2
Chronic
Aggregate
Risk
Assessment
.....................................
41
6.0
Cumulative
Risk
...........................................................
42
7.0
Incident
Data
.............................................................
43
8.0
Data
Needs
...............................................................
44
References
..................................................................
45
3
1.0
Executive
Summary
Hexazinone
[3
cyclohexyl
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
is
a
triazine
dione
herbicide
registered
for
use
on
alfalfa,
blueberries,
pasture
and
range
grasses,
pineapple,
and
sugarcane.
It
is
also
registered
for
use
on
ornamental
plants,
forest
trees,
and
noncrop
areas.
There
are
no
residential
uses
of
the
chemical.
Hexazinone
is
used
to
control
a
variety
of
weed
species
and
works
through
inhibition
of
photosynthesis.
Hexazinone
may
be
applied
for
pre
or
post
emergence
weed
control
by
layby,
directed
spray,
broadcast
spray,
or
basal
soil
treatments
and
can
be
applied
using
either
ground
or
aerial
equipment.
It
is
formulated
as
a
dry
flowable
(DF),
emulsifiable
concentrate
(EC),
granular
(G),
and
soluble
concentrate
(SC)
and
these
formulations
are
registered
for
food/
feed
uses.
The
range
of
percentage
of
active
ingredient
in
product
formulations
is
10
90%.
The
application
rates
range
from
1
4
lbs.
active
ingredient
per
acre
and
the
number
of
applications
typically
limited
to
one
per
year
or
per
crop
cycle.
Hexazinone
is
mainly
an
early
season
use,
pre
harvest
intervals
(PHIs)
of
180
234
days,
but
there
are
PHIs
of
30
days
for
some
uses.
There
are
approximately
400,000
pounds
of
active
ingredient
used
per
year.
Hexazinone
has
low
acute
toxicity
by
the
oral
(Category
III),
dermal
(Category
IV)
and
inhalation
routes
(Category
III).
It
has
low
acute
dermal
toxicity
(Category
IV)
and
causes
mild
skin
irritation
(Category
IV).
Hexazinone
is
not
a
skin
sensitizer.
However,
the
chemical
causes
severe
primary
eye
irritation
(Category
I).
In
chronic
studies
of
hexazinone's
toxicity,
body
weight
decrement
and
liver
toxicity,
including
changes
in
liver
related
clinical
chemistry
values,
and
microscopic
lesions
are
noted.
Hexazinone
is
classified
as
a
group
D
for
carcinogenic
potential,
not
classifiable
as
to
human
carcinogenicity.
Hexazinone
is
not
known
to
be
an
endocrine
disruptor
nor
is
there
evidence
of
neurotoxicity
in
the
toxicological
database.
The
hexazinone
rat
metabolism
study
indicated
that
the
chemical
is
rapidly
absorbed
and
excreted
and
there
is
essentially
no
difference
in
the
metabolism
between
males
and
females
at
high
or
low
doses.
A
small
amount
of
hexazinone
parent
and
two
major
metabolites,
metabolites
A
(3(
4
hydroxycyclohexyl)
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione)
and
C
(3(
4
hydroxycyclohexyl)
6(
methylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione)
were
recovered.
(Chemical
structures
begin
on
p.
24.)
There
is
no
evidence
of
qualitative
or
quantitative
susceptibility
in
prenatal
developmental
studies
in
the
rat
or
rabbit
or
in
post
natal
reproduction
studies
in
the
rat.
A
recently
submitted
rabbit
developmental
study
showed
fetal
weight
decrement
at
the
same
dose
as
maternal
weight
decrement.
A
developmental
neurotoxicity
study
for
hexazinone
is
not
required.
There
are
no
residual
uncertainties
for
pre
and/
or
post
natal
toxicity
in
any
of
the
available
studies
with
hexazinone.
Therefore,
the
FQPA
Safety
Factor
Committee
recommended
that
OPP
depart
from
the
default
10X
additional
safety
factor
and
instead
use
a
different
additional
safety
factor
of
1X
when
assessing
the
risk
of
hexazinone
to
human
health.
There
is
no
"special"
FQPA
safety
factor
necessary
to
protect
the
safety
of
infants
and
children
(no
enhanced
susceptibility
of
fetuses/
offspring).
4
Hexazinone
exhibits
systemic
and
liver
toxicity
in
studies
of
chronic
exposure.
Toxicological
endpoints
were
established
for
acute
and
chronic
dietary
exposure
scenarios
as
well
as
dermal
(intermediate
and
long
term)
and
inhalation
(short,
intermediate,
and
long
term)
exposure
scenarios.
Incidental
oral
endpoints
were
not
selected
because
there
are
no
residential
uses
for
hexazinone
and
a
short
term
dermal
endpoint
was
not
selected
because
no
hazard
was
identified.
No
adverse
effects
attributed
to
a
single
exposure
were
identified
for
the
general
population.
For
the
purposes
of
this
tolerance
reassessment
eligibility
decision
(TRED),
only
the
acute
and
chronic
dietary
exposure
scenarios
will
be
addressed.
Occupational
exposure
and
risk
were
considered
in
the
previous
reregistration
eligibility
decision
(RED,
1994).
An
acute
dietary
endpoint
was
identified
for
females
13
50
years
of
age.
The
endpoints
of
decreased
male
and
female
fetal
weight,
increased
incidence
of
kidneys
with
no
papilla
and
an
increased
incidence
of
misaligned
sternebrae
in
the
fetuses
were
identified
from
a
developmental
toxicity
study
in
rats.
Because
the
toxic
endpoint
for
acute
dietary
exposure
concerns
in
utero
exposure,
the
risk
assessment
is
performed
for
females
of
childbearing
age
(females
13
50),
since
only
members
of
this
group
are
at
risk
for
being
pregnant
at
the
time
of
exposure.
The
dose
selected
for
establishing
the
acute
reference
dose
(RfD)
is
the
developmental
No
Observed
Adverse
Effect
Level
(NOAEL)
of
400
mg/
kg/
day.
The
chronic
dietary
endpoint
was
identified
in
an
oral
toxicity
study
in
the
dog
and
is
based
upon
severe
body
weight
decrement,
clinical
chemistry
changes
in
the
liver
and
microscopic
lesions
in
the
liver
[NOAEL=
5.0
mg/
kg
bw/
day].
Tolerances
for
residues
of
hexazinone
in/
on
plant,
livestock,
and
processed
commodities
are
currently
expressed
in
terms
of
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone).
The
tolerance
expression
should
be
modified
to
include
the
specific
metabolites
(A,
B,
C,
C
2,
D,
E,
and
F)
by
the
appropriate
chemical
name
(See
Table
4,
p.
23).
Reassessed
tolerances
range
from
0.1
ppm
to
4.0
ppm.
Tolerances
are
reassessed
for
alfalfa
(hay
and
forage),
blueberry,
pineapple,
and
sugarcane
as
well
as
for
secondary
residues
in
cattle,
goat,
horse,
sheep,
and
milk.
HED
is
recommending
that
tolerances
be
revoked
for
livestock
fat,
hog
meat
and
meat
by
products
based
on
the
results
of
the
metabolism
and
feeding
studies.
HED
is
also
recommending
that
tolerances
for
pasture/
rangeland
grasses
be
revoked
due
to
a
lack
of
adequate
field
trial
data.
Tolerance
reassessment
for
secondary
residues
in
meat
and
milk
when
grass
is
a
significant
feed
item
could
not
be
completed.
However,
HED
has
determined
that
a
potential
diet
can
be
constructed
for
other
registered
feed
items,
and
subsequently
tolerances
for
meats
and
milk
can
be
reassessed.
It
is
important
to
note
that
the
tolerance
reassessment
and
risk
assessment
performed
in
this
document
assumes
the
tolerances
for
pasture/
rangeland
grasses
are
revoked
and
the
uses
withdrawn
from
the
label.
In
addition,
a
tolerance
is
proposed
for
alfalfa
seed
in
this
TRED.
Estimated
acute
dietary
(food
only)
risk
for
females
age
13
50
associated
with
the
use
of
hexazinone
does
not
exceed
the
Agency's
level
of
concern.
The
acute
dietary
risk
for
females
13
50
years
of
age
is
approximately
1%
of
the
acute
population
adjusted
dose
(aPAD).
The
chronic
dietary
(food
only)
risk
estimate
does
not
exceed
the
Agency's
level
of
concern
for
any
population
subgroups
examined
including
the
most
highly
exposed
sub
group,
children
1
6
years
5
N
N
N
N
O
O
of
age.
The
chronic
dietary
risk
for
this
subgroup
is
approximately
15%
of
the
chronic
PAD
and
approximately
4%
for
the
general
U.
S.
population.
Since
the
acute
and
chronic
dietary
exposure
assessments
utilized
tolerance
level
residue
values
and
assumed
100%
of
the
crops
are
treated,
risk
estimates
are
considered
upper
end.
Aggregate
acute
and
chronic
exposure
and
risk
estimates
include
the
contribution
of
risk
from
all
dietary
(food+
water)
sources.
Short
and
intermediate
term
aggregate
exposure
and
risk
assessments
were
not
performed
since
there
are
no
residential
uses
for
hexazinone.
Drinking
water
estimated
environmental
concentrations
(EECs)
were
derived
from
both
model
and
monitoring
results.
The
chemical
is
persistent
and
mobile
in
the
environment.
Hexazinone
parent,
drinking
water
degradate
G3170,
and
all
metabolites
with
conjoined
cyclohexyl
and
triazine
rings
were
included
in
the
drinking
water
exposure
and
risk
assessment.
(Chemical
structures
on
p.
23
and
31.)
The
FIRST
model
was
used
to
estimate
concentrations
of
hexazinone
and
its
metabolites
in
surface
water
using
model
parameters
for
alfalfa.
The
results
of
a
prospective
water
monitoring
study
were
used
to
estimate
concentration
of
the
chemical
in
groundwater.
Neither
acute
nor
chronic
aggregate
risk
exceed
the
Agency's
level
of
concern.
Therefore,
the
Agency
can
conclude
with
reasonable
certainty
that
residues
of
hexazinone
plus
its
metabolites
of
concern
would
not
likely
result
in
an
aggregate
risk
to
infants
and
children.
The
Agency
based
this
determination
on
a
comparison
of
estimated
concentration
of
hexazinone
and
its
metabolites
to
calculated
drinking
water
levels
of
comparison
or
"DWLOCs."
The
database
for
hexazinone
is
considered
adequate
for
risk
assessment,
however,
data
deficiencies
have
been
identified.
The
Agency
requires
a
28
day
inhalation
study.
Residue
chemistry
data
requirements
include
outstanding
label
amendments
(new
labels
should
reflect
cancelled
use
on
pasture/
rangeland
grasses)
and
a
field
rotational
crop
study
for
corn
and
wheat.
2.0
Physical
and
Chemical
Properties
Hexazinone
[3
cyclohexyl
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H
dione]
is
a
contact
and
residual
herbicide
used
to
control
a
broad
spectrum
of
weeds
including
woody
plants
found
in
alfalfa,
rangeland,
pastures,
woodlands,
pineapple,
sugarcane
and
blueberries.
Non
crop
areas
include
ornamental
plants
and
forests.
Hexazinone
interferes
with
electron
transport
in
chloroplast
membranes
which
allows
oxidation
of
plant
lipids
and
proteins.
Upon
exposure
to
the
chemical,
damaged
cell
membranes
leak,
causing
the
cells
to
dry
and
disintegrate.
Hexazinone
is
registered
for
pre
emergent,
post
emergence,
directed
spray
and
soil
applications.
Chemical
end
use
products
are
formulated
as
a
granular,
water
dispersible
granules,
emulsifiable
concentrates,
ready
to
use
liquids,
and
soluble
concentrates/
solids.
Products
are
applied
by
aerial,
broadcast,
and
directed
spray.
There
are
no
reported
impurities
of
toxicological
concern
in
hexazinone.
There
is
a
single
hexazinone
technical
[T]
product
registered
under
PC
Code
107201,
the
Dupont
98.7
%
T;
EPA
Reg.
No.
352
399.
(K.
Dockter,
Product
Chemistry
Chapter
for
the
Tolerance
6
Reassessment
Eligibility
Decision,
April
23,
2002.)
Identity:
3
cyclohexyl
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
Class:
Triazine
Empirical
formula:
C12
H20
N4
O2
Molecular
weight:
252.3
CAS
Registry
No.:
51235
04
2
Color:
White
Physical
state:
crystalline
solid
Odor:
mildly
pungent
MP:
113.5
C
Bulk
density:
0.61
g/
mL
Water
solubility:
2.98
g/
100g@
25
C
vapor
pressure:
1.9
x
10
7
mm
Hg@
25
C
log
Pow
:
2.76
Stability:
stable
in
slightly
acidic
or
alkaline
media
at
elevated
temperatures,
slowly
degrades
under
artificial
sunlight.
Approximately
1%
decomposition
when
stored
2
years
under
ambient
conditions.
There
is
the
potential
for
exposure
to
the
chemical
via
all
routes,
oral,
dermal
and
inhalation.
Hexazinone
has
low
vapor
pressure
but
high
water
solubility,
indicating
a
strong
potential
to
enter
and
remain
in
water
systems.
There
is
low
potential
for
bioaccumulation
based
on
this
chemical's
properties.
This
tolerance
reassessment
eligibility
decision
document
will
assess
the
exposure
and
risks
via
the
oral
route
(food
and
water
pathways)
only.
There
are
no
residential
uses
for
hexazinone.
Occupational
exposures
and
risk
were
considered
at
the
time
of
the
Reregistration
Eligibility
Document
(RED,
1994)
and
risk
mitigation
recommendations
were
made
at
that
time.
The
purpose
of
this
document
is
to
reassess
the
hexazinone
tolerances
in
accordance
with
FQPA.
7
3.0
Hazard
Characterization
3.1
Hazard
Profile
The
acute
toxicity
of
hexazinone
is
presented
in
Table
1.
All
studies
were
performed
using
hexazinone
technical
as
the
test
substance.
Table
1:
Acute
Toxicity
of
Hexazinone
Guideline
No./
Study
Type
MRID
No.
Results
Toxicity
Category
870.1100
Acute
oral
toxicity
41235004
LD50
=
1200
mg/
kg
III
870.1200
Acute
dermal
toxicity
00104974
LD50
>
5278
mg/
kg
IV
870.1300
Acute
inhalation
toxicity
41756701
(1990)
LC50
>
3.94
mg/
L(
4
hour)
III
870.2400
Acute
eye
irritation
00106003
Irreversible
corneal
opacity
I
870.2500
Acute
dermal
irritation
00106004
Mild
IV
870.2600
Skin
sensitization
41235005
Not
a
dermal
sensitizer
in
the
Buehler
test
in
Guinea
pigs
NA
The
toxicity
profile
for
hexazinone
is
shown
in
Table
2.
8
Table
2:
Toxicity
Profile
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
870.3100
90
Day
oral
toxicity
rats
0010977
(1973)
Dose:
0,
200,
1000
or
5000
ppm
(equivalent
to
0,
16.0/
16.4,
81.0/
87.3,
440/
451
mg/
kg/
day,
male/
female)
Acceptable
NOAEL
=
1000
ppm
(81.0/
87.3
mg/
kg/
day
male/
female)
LOAEL
=
5000
ppm
(440/
451
mg/
kg/
day
male/
female)
based
on
decreased
body
weight
and
food
efficiency.
870.3150
90
Day
oral
toxicity
in
non
rodents
00114484
(1973)
Doses
of
0,
200,
1000,
or
5000
ppm
(equivalent
to
0/
0,
5.1/
7.0,
25.9/
31.6,
122.5/
137.3
mg/
kg/
day,
males/
females)
Acceptable
NOAEL
=
1000
ppm
(equivalent
to
25.9/
31.6
mg/
kg/
day
for
males/
females).
LOAEL
=
5000
ppm
(equivalent
to
122.5/
137.3
mg/
kg/
day
in
males/
females)
based
on
decreased
body
weight
gains,
increased
relative
liver
weights,
and
increased
alkaline
phosphatase
levels
in
both
sexes
and
transiently
decreased
food
consumption
in
the
females.
870.3200
21/
28
Day
dermal
toxicity
in
rabbits
41309005
(1989)
Doses:
0,
50,
400,
or
1000
mg/
kg/
day
Acceptable
NOAEL
=
1000
mg/
kg/
day.
LOAEL
=
was
not
identified
for
systemic
and
dermal
toxicity.
870.3250
90
Day
dermal
toxicity
Not
required
870.3465
90
Day
inhalation
toxicity
The
90
day
inhalation
study
is
not
required,
however
a
28
Day
inhalation
study
is
required
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
9
870.3700a
Prenatal
developmental
in
rats
40397501
(1980)
Doses:
0,
40,
100,
400,
or
900
mg/
kg
Acceptable
Maternal
NOAEL
=
100
mg/
kg/
day
LOAEL
=
400
mg/
kg/
day
based
on
decreased
food
consumption
during
dosing
and
nominal
decreases
in
body
weight
gain
from
day
7
to
day
17
and
at
all
measured
intervals
between
and
at
900
mg/
kg/
day
mortality
and
decreased
body
weight
gains
and
food
consumption.
Developmental
NOAEL
=
400
mg/
kg/
day
LOAEL
=
900
mg/
kg/
day
and
at
900
mg/
kg/
day
an
increased
incidence
of
kidneys
with
no
papilla
(malformation),
and
an
increased
incidence
of
misaligned
sternebrae
(variation).
870.3700a
Prenatal
developmental
in
rats
00114486
(1974)
Doses:
0,
18.9,
94.5,
and
482.0
mg/
kg/
day
Unacceptable/
Upgradable
Maternal:
NOAEL
is
1000
ppm
(equivalent
to
94.5
mg/
kg/
day).
LOAEL
=
5000
ppm
(equivalent
to
482.0
mg/
kg/
day)
based
on
decreased
body
weights,
body
weight
gains,
and
food
efficiency.
Developmental:
NOAEL
=
5000
ppm
(equivalent
to
482.0
mg/
kg/
day).
LOAEL
was
not
observed.
870.3700b
Prenatal
developmental
in
rabbits
45677801
(2002)
Doses:
0,
50,
125,
175
mg/
kg/
day
Acceptable
Maternal:
NOAEL=
50
mg/
kg/
day.
LOAEL=
125
mg/
kg/
day
based
on
body
weight
gain
decrement,
decreased
food
consumption,
abortions,
death
and
clinical
signs
including
abnormal
gait
at
175
mg/
kg/
day.
Developmental:
NOAEL
=
50
mg/
kg/
day.
LOAEL=
125
mg/
kg/
day
based
on
mean
male
and
female
fetal
weight
decrement
and
female
fetal
weight
decrement.
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
10
870.3700b
Prenatal
developmental
in
rabbits
00028863
(1980)
Doses:
0,
20,
50,
or
125
mg/
kg/
day
Unacceptable/
Upgradable
Maternal
NOAEL
=
50
mg/
kg/
day
LOAEL
=
125
mg/
kg/
day
based
on
transient
decreases
in
food
consumption
and
body
weight
gains.
Developmental
NOAEL
=
50
mg/
kg/
day
LOAEL
=
125
mg/
kg/
day
based
on
possible
skeletal
abnormalities
and
total
abnormalies.
870.3800
Reproduction
and
fertility
effects
in
rats
42066501
(1991)
Acceptable
0,
200,
2000
or
5000
ppm
M:
0,
11.8,
117
or
294
mg/
kg/
day
F:
0,
14.3,
143
or
383
mg/
kg/
day
Parental/
Systemic
NOAEL
=
14.3
mg/
kg/
day
LOAEL
=
143
mg/
kg/
day
based
on
male
body
weight
decrement.
Reproductive
NOAEL
=
383
mg/
kg/
day
LOAEL
=
None
based
on
no
effects
on
or
organs
of
reproduction.
Offspring
NOAEL
=
14.3
mg/
kg/
day
LOAEL
=
143
mg/
kg/
day
based
on
reduced
female
pup
weight
at
birth
and
during
lactation.
870.4100a
Chronic
toxicity
in
rats
See
870.4300
870.4100b
Chronic
toxicity
dogs
42162301
(1991)
Doses:
0,
200,
1500,
or
6000
ppm
(equivalent
to
5.00/
4.97,
41.24/
37.6
and
161/
167
mg/
kg/
day,
male/
female.
Acceptable
NOAEL
=
200
ppm
(5.0/
4.97
mg/
kg/
day,
male/
female)
LOAEL
=
1500
ppm
(41.24
and
37.6
mg/
kg/
day,
respectively)
based
on
thinness
in
one
male
and
hepatotoxicity
as
evidenced
by
changes
in
clinical
chemistry
parameters
and
microscopic
lesions.
870.4200
Carcinogenicity
rats
See
below
870.4300
No
evidence
of
carcinogenicity
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
11
870.4200
Carcinogenicity
mice
00079203
(1981),
41359301
(1984),
42509301
(1992)
and
43202901
(1994)
Doses:
0,
0,
200,
2500
or
10,000
ppm
(equivalent
to
28/
34,
366/
450
and
1635/
1915
mg/
kg/
day,
male/
female)
Acceptable
NOAEL
=
200
ppm
(28/
450
mg/
kg/
day,
male/
female,
respectively)
LOAEL
=
2500
ppm
for
males
(equivalent
to
366
mg/
kg/
day)
based
on
gross
liver
nodules/
masses,
hyperplastic
nodules
in
the
liver
and
centrilobular
hepatocyte
hypertrophy
and
10,000
ppm
for
females
(equivalent
to
1915
mg/
kg/
day
[limit
dose])
based
on
decreased
body
weights,
increased
relative
liver/
gall
bladder
weights,
hyperplastic
nodules
and
centrilobular
hepatocyte
hypertrophy.
Insufficient
evidence
for
carcinogenicity
in
mice.
870.4300
Combined
chronic/
carcinogenicity/
rats
00108638
(1977)
Doses:
0,
200,
1000,
or
2500
ppm
(equivalent
to
0,
10.2/
12.5,
53.4/
67.5,
or
138/
179
mg/
kg/
day,
male/
female)
Acceptable
NOAEL
=
200
ppm
for
males
and
females
(10.2/
12.5
mg/
kg/
day,
male/
female).
LOAEL
=
1000
ppm
for
males
and
females
(equivalent
to
53.3/
67.5
mg/
kg/
day,
male/
female)
based
on
decreased
body
weight
and
food
efficiency
in
males
and
females.
In
males
at
2500
ppm
the
body
weight
decrement
and
food
efficiency
decrement
occurred
only
for
the
first
6
months
of
the
study.
The
carcinogenic
potential
of
hexazinone
is
considered
negative
in
rats.
Gene
mutation
870.5100;
Reverse
mutation
in
Salmonella
strains
40826201
(1977)
200,
400,
600,
800
and
1000
:
g/
plate
S9
and
400,
800,
1200,
1600
and
2000
:
g/
mL
+
S9
mix.
Unacceptable
No
mutagenic
potential
was
seen,
but
doses
insufficient
to
cause
cell
toxicity.
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
12
Gene
mutation
870.5300;
hamster
CHO
cells/
HPRT
assay
00076956
(1980)
Trial
1
were
2.0,
11.1,
13.1,
13.9
and
14.3
mM
S9
and
2.0,
7.9,
8.9,
9.3
and
9.9
mM
+S9.
Trial
2
were
2.0,
5.9,
11.1,
13.1
and
13.9
mM
S9
and
2.0,
7.9,
8.9,
9.3
and
9.9
mM
+
S9.
Acceptable
No
evidence
of
mutagenic
potential
at
cytotoxic
doses.
Cytogenics
870.5375;
Chromosomal
aberrations
in
hamster
CHO
cells
00130709
(1982)
In
Trial
1,
1.58,
3.94,
15.85
and
19.82
mM
S9
and
0.32,
3.17,
7.93
and
15.85
mM
+
S9.
In
Trial
2,
1.58,
3.94,
7.93
and
15.85
S9
0.32,
3.17,
7.93
and
15.85
mM
+
S9
Acceptable
Positive
for
structural
chromosomal
aberrations
with
and
without
S9.
Other
Effects
870.5385,
In
vivo
Rat
bone
marrow
cytogenics
assay
00131355
(1982)
Rat
doses:
1000,
2000
or
3000
mg/
kg
Unacceptable
No
evidence
of
mutagenic
potential,
but
insufficient
animals
and
cells
were
tested.
Other
Effects
870.5395
Mouse
bone
marrow
micronucleus
test
45124401
(2000)
Mouse
doses:
1000,
2000
and
3000
mg/
kg
Acceptable
No
evidence
of
clastogenic
or
aneugenic
effect
in
bone
marrow
at
toxic
doses.
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
13
Other
Effects
870.5550,
UDS
in
rat
hepatocytes
00130708
(1983)
Trial
1:
1
x
10
5
,
1
x
10
4
,
1
x
10
3
,
1
x
10
2
,
0.1,
1.0,
10.0
and
30.0
mM
and
Trial
2:
1
x
10
5
,
1
x
10
4
,
1
x
10
3
,
1
x
10
2
,
0.1,
1.0,
5.0,
10.0
and
30.0
mM.
Acceptable
No
evidence
of
mutagenic
potential
at
precipitating
dose
levels.
870.6200a
Acute
neurotoxicity
screening
battery
Not
required
870.6200b
Subchronic
neurotoxicity
screening
battery
Not
required.
870.6300
Developmental
neurotoxicity
Not
required.
870.7485
Metabolism
and
pharmacokinetics
00140162
&
00109237
(1980
&1982)
Acceptable
No
parent
was
seen
in
urine
or
feces,
which
was
rapidly
absorbed
and
excreted.
Two
identified
metabolites
resulted
from
hydroxylation
of
the
cyclohexyl
ring
and
differed
only
by
the
metabolic
conversion
of
the
6
dimethyl
amine
to
a
secondary
methyl
amine.
No
sex,
or
dose
related
differences
in
the
formation
and
excretion
of
these
metabolites
were
found.
870.7600
Dermal
penetration
Not
required
Special
studies
None
submitted
The
toxicological
database
for
hexazinone
is
considered
complete
for
hazard
characterization.
The
toxicity
profile
of
hexazinone
can
be
characterized
for
potential
reproductive,
developmental
and
neurological
effects.
Primary
effects
of
hexazinone
toxicity
include
body
weight
decrement
and
liver
toxicity.
There
is
no
evidence
of
developmental
or
14
reproductive
susceptibility
in
the
studies
for
the
chemical.
Hexazinone
is
considered
a
Group
D
carcinogen,
not
classifiable
as
to
carcinogenicity.
There
is
an
adequate
metabolism
study
in
the
rat.
However,
the
Agency
requires
a
28
day
inhalation
study
for
hexazinone
because
of
concern
for
potential
inhalation
exposure
based
on
the
use
pattern.
(D.
Anderson,
Toxicology
Disciplinary
Chapter,
May
30,
2002.)
Hexazinone
has
low
acute
toxicity
by
the
oral
(Category
III),
dermal
(Category
IV
)
and
inhalation
routes
(Category
III).
However,
primary
eye
irritation
is
severe,
causing
corneal
opacity
and
moderate
irritation
in
unwashed
eyes
(Category
I).
It
causes
mild
skin
irritation
(Category
IV)
and
is
not
a
skin
sensitizer
in
the
Guinea
pig.
The
21
day
dermal
study
in
the
rabbit
showed
no
systemic
toxicity
and
mild
dermal
irritation
at
the
limit
dose.
Body
weight
decrement,
decreased
food
consumption,
and
kidney
and
liver
effects
were
seen
in
acute
and
chronic
studies
with
hexazinone.
The
chronic
dog
and
mouse
studies
resulted
in
liver
toxicity.
Both
chronic
rat
studies
and
the
rat
reproduction
study
show
body
weight
decrement.
The
chronic
study
in
dogs
showed
severe
body
weight
decrement
in
addition
to
changes
in
liver
related
clinical
chemistry
values
and
microscopic
lesions
in
the
liver.
In
a
rat
reproduction
study,
pup
weight
decrement
occurred
at
the
same
dose
as
parental
body
weight
decrement.
No
other
reproductive
effects
were
seen
in
the
study.
The
rat
prenatal
developmental
toxicity
study
showed
fetal
weight
decrement
and
renal
malformations,
but
no
increased
susceptibility.
The
rabbit
prenatal
developmental
toxicity
study
developmental
effects
were
seen
at
the
same
dose
showing
maternal
toxicity;
no
susceptibility
was
identified
in
this
study.
Body
weight
decrement
was
seen
in
both
the
chronic
carcinogenicity
study
in
rats
and
mice.
The
mouse
carcinogenicity
study
showed
an
increased
trend
for
liver
carcinomas,
but
no
pair
wise
significant
increases
were
identified.
The
rat
study
showed
no
carcinogenic
potential.
Because
there
is
no
evidence
of
carcinogenicity
in
rats
and
insufficient
evidence
of
carcinogenicity
in
the
mouse,
the
RfD/
Peer
Review
Committee
classified
hexazinone
as
a
group
D
chemical,
not
classifiable
as
to
human
carcinogenicity.
Rat
metabolism
studies
showed
that
hexazinone
was
rapidly
absorbed
and
excreted
with
essentially
no
difference
in
the
metabolism
of
males
and
females
at
high
or
low
dose
levels.
Almost
no
parent
hexazinone
was
recovered
in
urine
or
feces.
Metabolites
A
(66%)
[3(
4
hydroxycyclohexyl)
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione]
and
C
(28%)
[3(
4
hydroxycyclohexyl)
6(
methylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione]
were
recovered
from
feces
and
urine,
in
addition
to
lesser
amounts
of
metabolite
B
(9%)
[(
3
(cyclohexyl)
6(
methylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione]
and
small
amounts
of
conjugated
products
in
urine
(<
5%).
These
metabolites
are
also
present
in
plant
and
animal
commodities
as
well
as
in
environmental
studies.
For
the
purposes
of
risk
assessment,
the
toxicity
of
the
metabolites
and/
or
degradates
were
assumed
to
be
equal
to
the
parent
hexazinone
due
to
similarity
in
structure.
However,
hexazinone
is
not
likely
to
be
toxicologically
related
to
15
other
triazine
pesticides.
The
Hazard
Identification
and
Review
Committee
(HIARC)
requested
a
28
day
inhalation
toxicity
study
with
hexazinone
because
of
the
concern
for
potential
inhalation
exposure
based
on
the
use
pattern.
3.2
FQPA
Considerations
The
toxicology
database
for
hexazinone
contains
acceptable
developmental
and
reproduction
studies
in
the
rat
and
in
the
rabbit;
there
is
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
in
the
fetuses
or
offspring
in
these
studies.
The
HIARC
concluded
that
a
developmental
neurotoxicity
study
with
hexazinone
is
not
required
because
there
is
no
evidence
of
neurotoxicity
in
the
database.
There
are
no
residual
uncertainties
identified
in
the
exposure
databases.
The
dietary
food
exposure
assessment
is
Tier
1,
screening
level,
which
is
based
on
tolerance
level
residues
and
assumed
100%
of
all
crops
are
treated
with
hexazinone.
The
dietary
drinking
water
assessment
uses
monitoring
data
(groundwater)
and
modeling
results
(surface
water)
based
on
chemicalspecific
data
and
includes
extrapolated
estimates
for
all
degradates
of
concern.
These
assessments
will
not
underestimate
the
exposure
and
risks
posed
by
hexazinone.
The
safety
factor
recommendation
is
based
on
the
assumption
that
the
use
of
hexazinone
on
pasture
and
rangeland
grasses
is
withdrawn
(due
to
lack
of
field
trial
residue
data
for
forage
and
hay)
and
that
all
established
tolerances
associated
with
this
use
are
revoked.
The
FQPA
SFC
recommends
OPP
depart
from
the
default
10X
additional
safety
factor
and
instead
use
a
different
additional
safety
factor
of
1X
to
assessing
exposure
and
risk
associated
with
the
use
of
hexazinone;
no
additional
traditional
safety
factors
are
needed
with
regard
to
the
completeness
of
the
hexazinone
toxicity
database
and
no
Special
FQPA
Safety
Factor
is
necessary
to
protect
the
safety
of
infants
and
children.
(B.
Tarplee,
Hexazinone
2
nd
Report
of
the
FQPA
Safety
Factor
Committee,
August
8,
2002.)
3.3
Dose
Response
Assessment
Toxicological
endpoints
were
established
for
exposure
scenarios
of
interest
to
this
risk
assessment.
For
this
tolerance
reassessment
eligibility
decision
for
hexazinone,
only
the
acute
and
chronic
dietary
exposure
scenarios
will
be
assessed.
Acute
dietary
exposure
to
the
general
population
is
not
included
in
this
assessment
since
there
was
no
appropriate
endpoint
attributable
to
a
single
dose
identified
in
the
database.
Three
toxicological
studies
determined
endpoint
doses
for
the
relevant
exposure
scenarios:
a
developmental
toxicity
study
in
the
rat
and
in
the
rabbit
and
a
chronic
feeding
study
in
the
dog.
The
HIARC
also
selected
endpoints
for
the
dermal
and
inhalation
routes
of
exposure.
However,
as
there
are
no
exposure
scenarios
pertaining
to
these
routes
of
exposure
assessed
in
this
action,
these
endpoints
are
not
listed
in
Table
3.
A
discussion
16
of
the
dose
response
relationships
for
acute
and
chronic
dietary
endpoints
follows
presentation
of
Table
3.
(Hexazinone
3
rd
Report
of
the
Hazard
Identification
Assessment
Review
Committee
(HIARC),
TXR
0051033,
August
12,
2002.)
17
Table
3:
Hazard
Endpoint
Selection
Exposure
Scenario
Dose
(mg/
kg/
day)
UF
/MOE
Hazard
and
Exposure
Based
Special
FQPA
Safety
Factor
Study
and
Endpoint
for
Risk
Assessment
Dietary
Risk
Assessments
Acute
Dietary
females
13
50
years
of
age
NOAEL
=
400
UF
=
100
Acute
RfD
=
4.0
mg/
kg/
day
1x
aPAD=
4.0
mg/
kg/
day
Developmental
Toxicity
Rat
Decreased
male
and
female
fetal
weight,
kidneys
with
no
papilla
(malformation)
and
misaligned
sternebrae
(variation)
Acute
Dietary
general
population
including
infants
and
children
An
appropriate
endpoint
attributable
to
a
single
dose
was
not
identified
in
the
oral
studies.
Chronic
Dietary
all
populations
NOAEL=
5.0
UF
=
100
Chronic
RfD
=
0.05
mg/
kg/
day
1x
cPAD=
0.05
mg/
kg/
day
Chronic
one
year
feeding
Dog
LOAEL
=
41.24
male;
37.57
female
mg/
kg/
day
based
on
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase.
Cancer
Group
D
Not
Classifiable
as
to
human
carcinogenicity
3.3.1
Acute
Reference
Dose
(RfD)
Females
13
50
The
study
selected
to
define
the
dose
response
relationship
for
risk
assessment
of
acute
dietary
exposure
to
females
13
50
is
a
developmental
toxicity
study
in
the
rat
(MRID
40397501).
In
this
study,
hexazinone
was
administered
orally
to
female
rats
at
dose
levels
of
0,
40,
100,
400,
or
900
mg/
kg
on
gestation
day
7
through
16.
There
were
no
treatment
related
changes
in
clinical
signs,
gross
pathology,
pregnancy
rate,
live
fetuses,
resorption,
pre
or
post
implantation
loss,
corpora
lutea,
or
implantations
noted
at
any
dose
level
tested
in
the
dams.
At
the
highest
dose
tested,
one
treatment
related
death,
alopecia
and
enlarged
stomach,
decreased
body
weight
gain
and
decreased
food
consumption
occurred.
The
maternal
LOAEL
is
400
mg/
kg/
day
based
on
decreased
food
consumption
during
dosing
and
nominal
decreases
in
body
weight
gain
from
day
7
to
day
17
and
at
all
measured
intervals
in
the
dosing
regimen.
The
maternal
NOAEL
is
100
18
mg/
kg/
day.
In
the
fetuses
at
the
highest
dose
tested
male
and
female
fetal
weights
were
decreased
and
there
was
an
increased
incidence
of
misaligned
sternebrae.
Furthermore,
an
increased
incidence
of
kidneys
with
no
papilla
was
observed.
Although
the
incidence
was
not
statistically
significant,
a
dose
related
trend
was
observed.
The
developmental
toxicity
LOAEL
is
900
mg/
kg/
day,
based
on
decreased
male
and
female
fetal
weight
and
increased
incidence
of
kidneys
with
no
papilla
(malformation),
and
an
increased
incidence
of
misaligned
sternebrae
(variation).
The
malformations
are
presumed
to
occur
after
a
single
dose
and
thus
appropriate
for
acute
risk
assessment.
The
dose
selected
for
establishing
the
acute
reference
dose
(aRfD)
for
females
13
50
is
the
developmental
NOAEL
of
400
mg/
kg/
day.
Because
the
toxic
endpoint
for
acute
dietary
exposure
concern
in
utero
exposure,
the
risk
assessment
is
performed
for
females
of
childbearing
age
(females
13
50),
since
only
members
of
this
group
are
at
risk
of
being
pregnant
at
the
time
of
exposure.
Traditional
uncertainty
factors
(UFs)
of
10X
(10X
intraspecies
variation;
10X
interspecies
extrapolation)
are
applied
to
the
RfD.
There
are
no
additional
traditional
or
"special"
uncertainty
factors
applied
to
the
RfD
(1X)
because
there
is
no
susceptibility
identified
in
the
hazard
database.
3.3.2
Chronic
Reference
Dose
(RfD)
The
study
selected
to
define
the
dose
response
relationship
for
risk
assessment
is
a
oneyear
chronic
dog
study
(MRID
42162301).
Hexazinone
was
administered
to
beagle
dogs
in
the
diet.
Time
weighted
average
doses
for
the
treated
groups
were
5.00,
41.24,
and
161.48
mg/
kg/
day,
respectively,
for
males
and
4.97,
37.57,
and
166.99
mg/
kg/
day,
respectively,
for
females.
All
animals
survived
to
scheduled
necropsy.
Treatment
related
clinical
signs
of
toxicity
included
the
observation
of
thinness,
decreased
body
weight,
and
decreased
food
consumption.
Clinical
chemistry
changes
such
as
moderate
macrocytic
anemia,
decreases
in
RBC
counts,
hemoglobin,
and
hematocrit
and
increases
in
MCV
and
MCH
in
one
or
both
sexes
throughout
the
study.
For
the
high
dose
animals,
decreases
in
absolute
testes
weights
in
males
and
kidney,
heart,
and
brain
weights
in
females
(
12%)
and
increases
in
relative
liver
weights
in
males
and
females
were
considered
due
to
lower
final
body
weights
of
these
animals
as
compared
with
controls.
Liver
effects
were
seen
in
the
high
dose
animal
group.
This
group
had
aspartate
aminotransferase
levels
140
203%
(p
#
0.05)
of
the
control
values
and
alanine
aminotransferase
levels
206
276%
(p
#
0.05)
of
the
control
values.
Alkaline
phosphatase
levels
were
also
significantly
(p
#
0.05)
increased
in
the
mid
dose
males
(259
409%
of
controls)
and
females
(163
194%
of
controls)
beginning
at
week
26
and
in
the
high
dose
males
(346
1363%
of
Acute
RfD
(Females
13
50)
=
400
mg/
kg/
day
=
4.0
mg/
kg/
day
100
(UF)
19
controls)
and
females
(307
559%
of
controls)
beginning
at
week
13.
Microscopic
lesions
in
the
liver
of
high
dose
animals
included
concentric
membranous
bodies
in
4
males
and
5
females,
centrilobular
single
cell
necrosis
in
3
males
and
3
females,
hepatocellular
pigment
in
3
males
and
3
females,
and
vacuolation
in
3
males
and
4
females.
In
addition
vacuolation
was
observed
in
one
mid
dose
male
and
pigment
and
membranous
bodies
were
each
observed
in
one
mid
dose
female.
These
lesions
were
not
seen
in
control
or
low
dose
animals.
The
study
selected
for
the
chronic
dietary
endpoint
is
of
the
appropriate
duration
for
assessing
long
term
exposure.
The
RfD/
peer
Review
Committee
chose
the
same
dose
and
endpoint
in
1994,
which
formed
the
basis
of
the
Chronic
RfD
for
the
1994
RED.
The
dose
selected
for
establishing
the
chronic
dietary
endpoint
is
the
NOAEL
of
5.0
mg/
kg/
day.
The
LOAEL
is
38
mg/
kg/
day
based
on
elevated
clinical
chemistry
values
(serum
alkaline
phosphatase,
serum
aspartate
aminotransferase),
other
changes
in
clinical
chemistry
values,
liver
microscopic
findings
and
body
weight
decrement
and
clinical
observation
of
thinness
in
one
male
(4
of
10
males
and
females
at
the
next
higher
dose).
An
uncertainty
factor
of
100
(10x
interspecies
and
10x
intra
species)
is
applied
to
the
endpoint.
3.4
Endocrine
Disruption
EPA
is
required
under
the
FFDCA,
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(including
all
pesticide
active
and
other
ingredients)
"may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(EDSTAC),
EPA
determined
that
there
was
scientific
bases
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(EDSP).
In
the
available
toxicity
studies
on
hexazinone,
there
was
no
evidence
of
endocrine
disruptor
effects.
When
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
hexazinone
may
be
subject
to
additional
screening
and/
or
testing
to
further
characterize
effects
related
to
endocrine
disruption.
Chronic
RfD
=
5.0
mg/
kg/
day
(NOAEL)
=
0.05
mg/
kg/
day
100
(UF)
20
4.0
Exposure
Assessment
and
Characterization
4.1
Summary
of
Registered
Use
Patterns
Hexazinone
[3
cyclohexyl
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
is
a
triazine
dione
herbicide
registered
for
use
on
alfalfa,
blueberries,
pasture
and
range
grasses,
pineapple,
and
sugarcane.
It
is
also
registered
for
use
on
ornamental
plants,
forest
trees,
and
non
crop
areas.
Hexazinone
is
used
to
control
a
variety
of
weed
species
including
geratum,
alder,
and
alexander
grass
and
works
through
inhibition
of
photosynthesis.
Hexazinone
is
a
proprietary
chemical
of
E.
I.
du
Pont
de
Nemours
and
Company,
Inc.
which
is
the
sole
producer
and
primary
registrant
of
this
broad
spectrum
herbicide.
Hexazinone
formulations,
sold
under
the
trade
name
Velpar®,
may
be
applied
pre
or
post
emergence
by
layby,
broadcast,
directed
spray,
or
basal
soil
treatments
using
ground
or
aerial
equipment.
(J.
Punzi,
Hexazinone
Tolerance
Reassessment
Eligibility
Decision
Residue
Chemistry
Chapter,
DP
Barcode
D279899,
May
20,
2002.)
Hexazinone
is
formulated
as
a
dry
flowable
(DF),
emulsifiable
concentrate
(EC),
soluble
concentrate
(SC)
and
as
a
granular
(G)
and
these
end
use
products
are
registered
to
DuPont
for
food/
feed
uses.
The
range
of
percentage
of
active
ingredient
in
the
product
formulations
is
10
90%.
The
application
rates
range
from
1
4
lbs.
active
ingredient
per
acre.
The
number
of
applications
per
year
(or
season)
are
typically
limited
to
one
per
year.
Hexazinone
is
mainly
an
early
season
use,
PHIs
range
from
180
234
days,
but
PHIs
are
30
60
days
for
alfalfa
and
blueberry,
respectively.
A
profile
of
hexazinone
usage
has
been
developed
by
the
OPP
Biological
and
Economic
Analysis
Division
(BEAD).
The
use
profile
is
based
on
data
from
US
EPA,
USDA
and
the
National
Center
for
Food
and
Agricultural
Policy.
From
1991
through
2000,
the
total
annual
domestic
usage
of
hexazinone
averaged
approximately
400,000
pounds
of
active
ingredient
for
over
700,000
acres
treated.
Hexazinone's
largest
markets
in
terms
of
total
pounds
active
ingredient
includes
alfalfa,
woodland,
and
pasture
and
rangeland.
Alfalfa
is
the
crop
with
the
highest
percent
of
crop
treated.
Crops
with
less
than
1
percent
treated
include
blueberries,
other
hay,
and
sugarcane.
(F.
Hernandez,
Quantitative
Usage
Analysis
for
Hexazinone,
September
10,
2001.)
There
are
no
registered
uses
for
this
chemical
at
residential
sites.
Occupational
exposures
are
not
considered
in
this
tolerance
reassessment
action.
The
populations
of
concern
for
this
assessment
are
those
who
may
be
exposed
through
consuming
crops
treated
with
hexazinone
or
consuming
water
containing
hexazinone
residues.
4.2
Dietary
(Food)
Exposure/
Risk
Pathway
Tolerance
reassessment
and
dietary
risk
assessment
for
hexazinone
is
based
on
the
residue
data
summarized
in
this
section.
Tolerances
for
residues
of
hexazinone
in/
on
plant,
21
animal,
and
processed
commodities
are
currently
expressed
in
terms
of
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone).
Permanent
tolerances
are
established
for
plant
and
animal
commodities
under
40
CFR
§180.396(
a).
Hexazinone
tolerances
with
regional
(Florida
sugarcane)
registrations
are
established
under
40
CFR
§180.396(
c).
Tolerances
exist
for
blueberry,
pineapple,
sugarcane,
alfalfa
and
grasses
as
well
and
meats
and
milk.
Current
tolerances
range
from
0.02
to
0.5
ppm
on
raw
agricultural
commodities,
8.0
10.0
ppm
on
agricultural
feed
items,
and
are
0.1
ppm
for
secondary
residues
in
meats
and
milk.
HED
is
requesting
the
registrant
to
propose
a
tolerance
for
hexazinone
residues
of
concern
in/
on
alfalfa
seed
of
2.0
ppm
based
upon
a
residue
field
trial
study
at
1.5x
the
maximum
registered
rate
on
alfalfa
grown
for
seed.
Reassessed
tolerances
range
from
0.1
to
4.0
ppm.
(J.
Punzi,
Hexazinone
Tolerance
Reassessment
Eligibility
Decision
Residue
Chemistry
Chapter,
DP
Barcode
D279899,
May
20,
2002.)
4.2.1
Residue
Profile
The
HED
Metabolism
Assessment
Review
Committee
(MARC)
has
reviewed
the
hexazinone
toxicology
and
metabolism
data
(meeting
dates
1/
29/
02
and
3/
12/
02)
and
recommends
that
the
tolerance
expression
for
plant
material
should
include
hexazinone
(parent)
and
metabolites
A,
B,
C,
D,
and
E.
The
tolerance
expression
for
milk
should
include
hexazinone
(parent)
and
metabolites
B,
C,
C
2,
and
F,
and
the
tolerance
expression
for
ruminant
tissue
should
include
hexazinone
(parent)
and
metabolites
B
and
F.
The
tolerance
expression
should
be
modified
to
include
the
specific
metabolites
(A,
B,
C,
C
2,
D,
E
and
F)
by
the
appropriate
chemical
name
(See
Table
4).
The
Agency
has
determined
that
tolerances
for
hexazinone
residues
in
eggs
and
poultry
tissue
are
not
required
based
on
the
results
of
the
respective
poultry
metabolism
and
feeding
studies
(CFR
§180.6(
a)(
3)).
(S.
Kinard,
The
Outcome
of
the
HED
Metabolism
Review
Committee
for
Water,
April
25,
2002.)
Adequate
residue
data
have
been
submitted
to
reassess
the
tolerances
for
alfalfa
(seed,
forage,
hay),
blueberries,
pineapple,
sugarcane,
and
associated
livestock
commodities
(meat,
milk).
Residue
data
are
not
adequate
to
reassess
tolerances
for
pasture
and
rangeland
grass
(forage
and
hay)
and
a
recommendation
has
been
made
to
revoke
those
tolerances
and
to
withdraw
this
use
from
the
product
labels.
Data
depicting
magnitude
of
the
residues
of
hexazinone
and
metabolites
A,
B,
C,
D,
and
E
in/
on
grass
forage
and
hay
harvested
the
day
following
a
single
broadcast
application
of
representative
formulations
at
1.125
lb
ai/
A
are
listed
as
data
requirements
in
the
Residue
Chemistry
chapter.
However,
these
data
are
not
listed
as
required
in
this
action
because
the
tolerance
reassessment
and
risk
assessment
will
assume
that
the
tolerances
are
revoked
and
the
uses
withdrawn
from
the
label
due
to
the
lack
of
field
trial
data.
The
MARC
also
recommended
that
for
the
purposes
of
risk
assessment
estimates
of
dietary
exposure
and
risk
should
be
based
on
residue
estimates
of
hexazinone
(parent)
and
metabolites
B,
C,
C
1,
C
2,
and
F
for
ruminant
commodities
and
metabolites
A,
B,
C,
D,
and
E
for
plant
commodities.
The
metabolites
and
parent
hexazinone
are
assumed
to
have
equal
22
toxicity
based
upon
similarity
in
chemical
structure.
Metabolism
in
Plants
and
Animals
The
qualitative
nature
of
hexazinone
residue
in
plants
and
animals
is
adequately
understood
based
on
submitted
metabolism
studies
in
alfalfa,
pineapple,
sugarcane,
ruminants,
and
poultry.
Plants:
Plant
metabolism
studies
indicate
that
root
uptake
is
the
principal
mechanism
for
the
absorption
of
hexazinone
by
plants
from
soils.
Hexazinone
is
translocated
through
the
xylem
to
the
foliage
where
it
blocks
the
photosynthetic
process.
Hexazinone
is
metabolized
by
hydroxylation
to
metabolite
A
which
is
then
metabolized
to
metabolite
C
by
demethylation,
and
to
metabolite
E
after
oxidation.
In
an
alfalfa
metabolism
study,
alfalfa
was
sprayed
with
[
14
C]
hexazinone
dissolved
in
water
at
an
application
rate
equivalent
to
1.0
lb
ai/
100
gal/
A.
Alfalfa
samples
were
collected
at
two,
three,
and
six
months
after
treatment.
Total
radioactive
residues
(TRR),
calculated
as
hexazinone,
declined
at
each
sampling
interval,
and
were
0.6,
0.5,
and
0.1
ppm
(95,
84,
and
80%
respectively).
Analysis
of
the
two
month
alfalfa
cutting
identified
hexazinone
(2.7%
TRR),
free
metabolite
A
(7.1%
TRR),
free
metabolite
B
(0.7%
TRR),
and
conjugated
metabolites
A,
B,
and
C
(4.5%
TRR).
The
remaining
radioactive
residues
were
found
in
water
soluble,
polar
materials
comprised
of
amino
acids,
sugars,
polybasic
acids,
and
smaller
amounts
of
natural
products.
In
a
pineapple
metabolism
study,
94
99%
of
TRR
was
extractable
with
the
following
components
identified
in
the
pulp:
hexazinone
(0.8
1.8%
TRR),
metabolite
A
(23
28%
TRR),
metabolite
C
(13
15%
TRR),
metabolite
D
(16
21%
TRR),
and
metabolite
F
(1
2%
TRR).
The
following
components
were
identified
in
sugarcane:
metabolite
E
(30%
TRR),
metabolite
C
(23%
TRR),
metabolite
A
(14%
TRR),
metabolite
B
(1%
TRR),
metabolite
D
(3%
TRR),
and
hexazinone
(<
1%
TRR).
Animals:
A
lactating
goat
was
dosed
orally
with
[
14
C]
hexazinone
radiolabeled
in
the
triazine
ring
at
a
dose
rate
of
136.4
mg/
day,
equivalent
to
2.2
mg/
kg/
body
weight
for
five
consecutive
days.
TRRs,
expressed
as
hexazinone
equivalents,
were
6.74
ppm
in
milk,
3.03
ppm
in
liver,
2.54
ppm
in
kidney,
0.27
ppm
in
muscle,
and
0.03
ppm
in
fat.
Residues
were
adequately
extracted,
characterized,
and
identified,
and
on
this
basis
the
MARC
concluded
that
the
hexazinone
tolerance
expression
for
milk
should
include
hexazinone
plus
metabolites
B,
C,
C
2.
The
MARC
also
concluded
that
the
hexazinone
tolerance
expression
for
ruminant
tissue
should
include
hexazinone
plus
metabolites
B
and
F
and
that
residues
of
hexazinone
and
metabolites
B,
C,
C
1,
C
2,
and
F
should
be
taken
into
account
for
risk
assessment.
In
a
poultry
metabolism
study
five
laying
hens
were
dosed
orally
at
6.9
mg/
day
with
carbonyl
labeled
[
14
C]
hexazinone
for
six
consecutive
days.
The
daily
dose
rate
was
equivalent
to
57
ppm
in
the
feed,
which
is
38x
the
maximum
theoretical
dietary
burden.
No
single
metabolite
in
edible
poultry
tissue
was
greater
than
0.04
ppm,
and
unidentified
metabolites
represented
less
than
0.05
ppm
in
all
edible
tissues.
For
these
reasons,
poultry
tolerances
are
not
necessary.
23
N
N
N
O
O
CH
3
N
CH
3
CH
3
N
N
N
O
O
CH
3
N
CH
3
CH
3
HO
N
N
N
O
O
CH
3
N
H
CH
3
Table
4:
Chemical
Structures
of
Hexazinone
and
its
Regulated
Metabolites
(Metabolites
A
through
F)
Common
Name/
Code
Chemical
name
Structure
Hexazinone
3
cyclohexyl
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H
dione
Metabolite
A
3(
4
hydroxycyclohexyl)
6
(dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
Metabolite
A
1
is
hydroxylated
at
the
2
position
of
the
cyclohexyl
ring;
Metabolite
A
2
is
hydroxylated
at
the
3
position
of
the
cyclohexyl
ring.
Metabolite
B
3
cyclohexyl
6(
methylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H
dione
Common
Name/
Code
Chemical
name
Structure
24
N
N
N
O
O
CH
3
N
H
CH
3
HO
N
N
NH
O
O
CH
3
O
N
N
NH
O
O
CH
3
O
HO
N
N
N
O
O
CH
3
NH
2
Metabolite
C
3(
4
hydroxycyclohexyl)
6
methylamino
1
methyl
1,3,5
triazine
2,4(
1H,
3H
dione
Metabolite
C
1
is
hydroxylated
at
the
2
position
of
the
cyclohexyl
ring;
Metabolite
C
2
is
hydroxylated
at
the
3
position
of
the
cyclohexyl
ring.
Metabolite
D
3
cyclohexyl
1
methyl
1,3,5
triazine
2,4,6(
1H,
3H,
5H)
trione
Metabolite
E
3(
4
hydroxycyclohexyl)
1
methyl
1,3,5
triazine
2,4,6(
1H,
3H,
5H)
trione
Metabolite
F
3
cyclohexyl
6
amino
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
25
Residue
Analytical
Methods
Plant
Matrices:
Adequate
methods
are
available
for
purposes
of
enforcement
of
tolerances
and
data
collection
for
residues
of
hexazinone
and
metabolites
A,
B,
C,
D,
and
E
in/
on
plant
commodities.
For
tolerance
enforcement,
the
Pesticide
Analytical
Manual
(PAM)
Volume
II
lists
Method
I
as
available
for
the
determination
of
hexazinone
residues
of
concern
in/
on
plant
commodities.
The
combined
limit
of
quantitation
(LOQ)
for
hexazinone
residues
(parent
and
metabolites)
by
Method
I
in
PAM
Volume
II,
is
0.55
ppm.
For
data
collection,
the
registrant
utilized
Methods
92013
V2
and
92013
V3
during
analyses
of
samples
collected
from
a
recent
field
residue
study
submission
on
alfalfa.
Methods
92013
V2
and
92013
V3
have
been
deemed
adequate
for
data
collection
based
on
acceptable
method
validation
and
concurrent
recovery
data.
Animal
Tissue
/
Milk:
The
registrant
has
proposed
a
liquid
chromotography/
mass
spectroscopy
(LC/
MS)
method
(AMR
3783
96)
as
an
enforcement
method
for
livestock
commodities.
The
proposed
method
would
determine
residues
of
parent
hexazinone,
metabolite
B,
metabolite
C
and
its
isomer
(C
2),
and
metabolite
F
in
milk.
In
livestock
tissues,
Method
AMR
3783
96
would
determine
residues
of
parent
hexazinone,
metabolite
B,
and
metabolite
F.
The
reported
limits
of
quantitation
(LOQ)
s
were
0.02
ppm
for
hexazinone
and
metabolite
B
and
0.05
ppm
for
metabolites
C,
C
2,
and
F.
This
method
has
been
subjected
to
a
successful
independent
laboratory
validation
(ILV)
and
a
radiovalidation
study
and,
if
method
validation
by
the
Agency
is
successful,
the
method
will
be
proposed
for
inclusion
in
PAM
Volume
II
(no
additional
data
concerning
this
guideline
topic
will
be
required
for
reregistration).
Multi
Residue
Methods
The
reregistration
requirements
for
multiresidue
methods
data
are
fulfilled.
However,
the
10/
99
FDA
PESTDATA
database
(PAM
Volume
I,
Appendix
I)
indicates
that
hexazinone
(and
metabolites
A,
B,
C,
D,
and
E)
are
only
partially
recovered
(50
80%)
using
Multiresidue
Method
Sections
302
(Luke
Method;
Protocol
D)
and
are
not
recovered
using
Sections
303
(Mills,
Onley,
Gaither;
Protocol
E
nonfatty
foods)
and
304
(Mills;
Protocol
E
fatty
foods).
Field
Trial
Data
Reassessed
tolerances
and
the
dietary
risk
assessment
are
based
on
field
trail
data
conducted
on
blueberries,
alfalfa,
pineapple,
and
sugarcane.
Pending
label
revisions
for
certain
crops,
the
reregistration
requirements
for
data
depicting
"magnitude
of
the
residue"
in/
on
the
following
raw
agricultural
commodities
(RACs)
are
satisfied:
alfalfa
forage,
alfalfa
hay,
alfalfa
seed,
blueberries,
pineapple,
and
sugarcane.
An
adequate
number
of
field
trials
have
been
conducted
for
these
RACs,
and
the
trials
were
conducted
using
registered
hexazinone
formulation(
s)
at
the
maximum
registered
rate.
However,
the
reregistration
requirements
for
data
depicting
magnitude
of
the
residue
in/
on
grass
forage
and
grass
hay
are
not
satisfied.
The
lack
of
26
these
data
prevent
calculation
of
a
maximum
theoretical
dietary
burden
(MTDB)
for
livestock
which
includes
these
feed
items.
The
Health
Effects
Division
(HED)
is
recommending
that
in
order
to
reassess
the
established
hexazinone
tolerances
for
milk
and
the
fat,
meat,
and
meat
byproducts
of
livestock
and
to
compute
a
maximum
theoretical
dietary
burden
(MTDB)
of
hexazinone
to
livestock,
uses
on
pasture
and
rangeland
grasses
must
be
revoked
and
the
uses
withdrawn.
A
MTDB
could
not
be
calculated
including
grass
and
grass
hay
since
additional
residue
data
are
required
for
use
patterns
in
which
significant
residues
are
expected
in/
on
the
RACs.
HED
recognizes
that
the
estimated
100,000
acres
of
pasture
and
rangeland
treated
with
hexazinone
is
relatively
low.
However,
since
grass
and
grass
hay
are
considered
major
components
of
ruminant
diets
(up
to
60%
of
the
diet
per
current
OPPTS
GLN)
a
MTDB
for
livestock
could
not
be
developed
when
grasses
are
included
in
the
registered
uses.
Therefore,
it
is
important
to
note
that
the
tolerance
reassessment
and
risk
assessment
presented
in
this
document
does
not
include
the
use
of
hexazinone
on
pasture/
rangeland
grasses;
it
assumes
that
these
tolerances
are
revoked
and
the
uses
withdrawn
from
the
label.
However,
HED
has
determined
that
a
MTDB
could
be
constructed
from
other
potential
feed
items
for
livestock
and
subsequently
tolerances
for
meats
and
milk
can
be
reassessed.
Reassessed
tolerances
range
from
0.1
ppm
to
4.0
ppm.
Tolerances
are
not
currently
needed
for
livestock
fat,
hog
meat,
and
hogmeat
by
products
due
to
the
results
of
metabolism
and
feeding
studies.
Blueberries:
Data
indicate
that
the
combined
residues
of
hexazinone
and
its
regulated
metabolites,
as
measured
by
the
data
collection
method
were
less
than
the
detection
level
(<
0.05
ppm
for
each
compound/
metabolite)
in/
on:
(1)
12
samples
of
lowbush
blueberries
harvested
433
446
days
following
a
single
application
of
the
2
lb/
gal
EC
or
90%
SC
formulation
at
3
or
6
lb
ai/
A
(1.5
or
3.0x
the
maximum
registered
rate)
using
ground
or
aerial
equipment;
and
(2)
12
samples
of
highbush
blueberries
harvested
68
97
days
following
a
single
application
of
the
2
lb/
gal
EC
or
90%
SC
formulation
at
2
or
4
lb
ai/
A
(0.8
or
1.3x
the
maximum
registered
rate).
Based
on
the
combined
LOQs
(0.55
ppm)
of
the
enforcement
method,
HED
is
now
recommending
that
the
RAC
tolerance
be
reassessed
from
0.2
ppm
to
0.6
ppm.
Pineapple:
Data
indicate
that
the
combined
residues
of
hexazinone
and
its
regulated
metabolites,
as
measured
by
the
data
collection
method,
were
less
than
the
detection
level
(<
0.05
ppm
for
each
compound/
metabolite)
in/
on
pineapple
fruits
harvested
at
a
minimum
PHI
of
181
days
following
five
ground
applications
of
a
representative
hexazinone
formulation
at
0.45
0.9
lb
ai/
A
for
a
total
rate
of
3.6
lb
ai/
A.
Based
on
the
combined
LOQs
(0.55
ppm)
of
the
enforcement
method,
HED
is
now
recommending
that
the
RAC
tolerance
be
reassessed
from
0.5
ppm
to
0.6
ppm.
Sugarcane:
Data
indicate
that
the
combined
residues
of
hexazinone
and
its
regulated
metabolites,
as
measured
by
the
data
collection
method,
were
less
than
the
detection
level
(<
0.05
ppm
for
each
compound/
metabolite)
in/
on
samples
of
sugarcane
treated
with
the
90%
SC
formulation
of
hexazinone.
In
Hawaii,
sugarcane
was
harvested
179
181
days
following
a
total
27
of
four
applications
(one
pre
emergence
application
at
1.35
or
1.47
lb
ai/
A,
a
post
emergence
application
at
0.45
lb
ai/
A
per
application,
followed
by
two
post
emergence
applications
at
1.8
lb
ai/
A
per
application)
for
a
total
rate
of
5.4
5.5
lb
ai/
A
per
season
(1.5x
the
maximum
seasonal
rate
in
HI).
Similar
results
were
found
in
field
trials
in
Texas
and
Puerto
Rico.
Based
on
the
combined
LOQs
(0.55
ppm)
of
the
enforcement
method,
HED
is
now
recommending
that
the
RAC
tolerance
be
reassessed
from
0.2
ppm
to
0.6
ppm.
Alfalfa:
Data
indicate
that
the
combined
residues
of
hexazinone
and
its
regulated
metabolites
did
not
exceed
the
established
tolerances
of
2.0
ppm
in/
on
alfalfa
forage
and
8.0
ppm
in/
on
alfalfa
hay
harvested
29
31
days
following
a
single
broadcast
dormant
or
non
dormant
application
of
the
2
lb/
gal
EC
or
90%
SC
formulation
at
1.5
lb
ai/
A
(~
1x).
The
maximum
combined
residues
in/
on
treated
samples
were
<1.87
ppm
and
<3.33
ppm
for
alfalfa
forage
and
hay,
respectively.
Based
on
these
data,
the
established
tolerance
for
alfalfa
forage
is
reassessed
at
its
existing
level
of
2.0
ppm;
however,
the
tolerance
for
alfalfa
hay
should
be
lowered
from
8.0
ppm
to
4.0
ppm.
Data
indicate
that
the
combined
residues
of
hexazinone
and
its
regulated
metabolites
ranged
from
<1.30
ppm
(sum
of
the
LOQs)
to
<1.46
ppm
in/
on
alfalfa
seed
following
a
single
broadcast
dormant
application
of
the
2
lb/
gal
EC
or
90%
SC
formulation
at
0.75
lb
ai/
A
(1.5x
the
maximum
registered
rate
on
alfalfa
grown
for
seed).
Processing
Data
Pineapple:
Residues
of
hexazinone
and
its
regulated
metabolites
did
not
concentrate
in
pineapple
juice.
Metabolite
B
concentrated
(3x)
in
process
residue,
based
on
quantified
residues
of
0.06
ppm
in
pineapple
process
residue
and
0.02
ppm
in/
on
pineapple
RAC
after
treatment
with
hexazinone
at
a
1x
rate.
Sugarcane:
Residues
declined
in
raw
sugar
(reduction
factor
of
0.2x)
and
processed
sugar
(reduction
factor
of
0.2x).
The
maximum
average
combined
residue
of
hexazinone
and
its
regulated
metabolites
was
1.92
ppm
for
"A
molasses."
Secondary
Residue
/
Livestock
Commodities
Poultry:
Based
on
the
results
of
a
poultry
metabolism
study,
the
Agency
has
determined
that
tolerances
(and
dietary
risk
assessment)
for
hexazinone
residues
in
eggs
and
poultry
tissues
are
not
required
under
the
provision
of
Category
3,
40
CFR
§180.6(
a)(
3)
In
the
poultry
study,
liver
tissue
contained
the
highest
TRR
(0.19
ppm).
Considering
that
the
feeding
level
was
38x
of
the
maximum
theoretical
dietary
burden,
the
maximum
residue
in
poultry
tissue
would
be
0.005
ppm,
an
order
of
magnitude
below
the
limit
of
detection
for
hexazinone
metabolites.
Ruminants:
The
results
of
a
ruminant
(goat)
metabolism
study
suggested
a
very
significant
transfer
of
hexazinone
residues
of
concern
to
meat
and
milk.
Hexazinone
residues
of
concern
may
transfer
to
milk
and
edible
tissues
of
livestock
animals
as
a
result
of
ingestion
of
treated
feed
items
such
as:
alfalfa
forage,
hay,
meal,
and
silage;
pineapple
process
residue;
and
28
sugarcane
molasses.
Tolerances
and
risk
assessment
for
hexazinone
and
metabolites
in
milk,
meat
and
meat
byproducts
are
based
on
an
estimate
of
exposure
or
"dietary
burden"
to
livestock
from
the
above
feed
items
and
an
estimate
of
the
level
of
residue
"transfer"
to
milk
and
meat
that
may
occur.
The
rate
of
transfer
of
hexazinone
and
metabolites
is
based
on
the
results
of
a
feeding
study
in
dairy
cattle.
Based
on
residue
estimates
for
alfalfa
forage,
alfalfa
hay,
and
sugarcane
molasses
(and
excluding
the
current
registration
for
grass
and
grass
hay)
a
maximum
dietary
burden
of
4.64
ppm
estimated
for
ruminants
forms
the
basis
for
tolerances
in
milk
(0.2
ppm),
meat
(0.1
ppm)
and
meat
byproducts
(0.1
ppm).
Residues
in
ruminant
fat
and
hog
commodities
are
not
expected
and
a
revocation
of
tolerance
is
recommended
under
the
provision
of
Category
3,
40
CFR
§180.6(
a)(
3).
4.2.2
Acute
Dietary
Exposure
(Females
13
50)
Acute
dietary
(food)
risk
estimates
associated
with
the
use
of
hexazinone
and
its
metabolites
do
not
exceed
the
Agency's
level
of
concern
(>
100%
of
the
aPAD)
for
females
13
50
years
of
age.
The
acute
dietary
risk
estimate
for
females
13
50
years
of
age
is
approximately
1%
of
the
acute
Population
Adjusted
Dose
(aPAD).
The
acute
dietary
exposure
assessment
for
hexazinone
is
a
tier
I
analysis.
This
is
the
most
conservative
type
of
analysis
assuming
that
residues
on
foods
as
consumed
are
equal
to
the
tolerance
levels
and
that
100%
of
each
crop
is
treated.
The
tolerance
values
for
hexazinone
in/
on
blueberry,
pineapple,
and
sugarcane
are
based
on
the
analytical
method's
limit
of
quantitation
(LOQ)
and
all
studies
resulted
in
non
detectable
residues.
The
same
residue
data,
therefore,
are
used
in
both
the
acute
and
chronic
analysis.
(J.
Punzi,
Revised
Acute
and
Chronic
Dietary
Exposure
Assessments
for
the
TRED,
July
30,
2002.)
The
hexazinone
acute
dietary
exposure
assessment
was
conduced
using
the
Dietary
Exposure
Evaluation
Model
(DEEM
TM
)
software
Version
7.76,
which
incorporates
consumption
data
from
USDA's
Continuing
Survey
of
Food
Intake
by
Individuals
(CSFII),
1989
92.
The
1989
92
data
are
based
on
the
reported
consumption
of
more
than
10,000
individuals
over
three
consecutive
days,
and
therefore
represent
more
than
30,000
unique
person
days
of
data.
Foods
as
consumed
(e.
g.,
apple
pie)
are
linked
to
raw
agricultural
commodities
and
their
food
forms
(e.
g.,
apples
cooked/
canned
or
wheat
flour)
by
recipe
translation
files
internal
to
the
DEEM
software.
Consumption
data
are
retained
as
individual
consumption
events
for
acute
exposure
assessment.
For
acute
exposure
assessments,
individual
one
day
food
consumption
data
are
used
on
an
individual
by
individual
basis.
The
reported
consumption
amounts
of
each
food
item
can
be
multiplied
by
a
residue
point
estimate
and
summed
to
obtain
a
total
daily
pesticide
exposure
for
a
deterministic
(Tier
1
or
2)
exposure
assessment,
or
matched
in
multiple
random
pairings
with
residue
values
and
then
summed
in
a
probabilistic
(Tier
3/
4)
assessment.
The
resulting
distribution
of
exposure
is
expressed
as
a
percentage
of
the
aPAD
in
both
a
user
(i.
e.,
those
who
reported
eating
relevant
commodities/
food
forms)
and
a
per
capita
(i.
e.,
those
who
reported
eating
the
relevant
commodities
as
well
as
those
who
did
not)
basis.
In
accordance
with
HED
29
policy,
per
capita
exposure
and
risk
are
reported
for
all
tiers
of
analysis.
The
acute
population
adjusted
dose
(aPAD)
is
calculated
as
the
acute
RfD
divided
by
the
chemical
specific
FQPA
safety
factor
(1x).
The
calculated
acute
exposure
(residue
x
consumption)
was
compared
to
an
aPAD
of
4.0
mg/
kg/
day.
The
results
are
displayed
in
Table
5.
Table
5:
Summary
of
Acute
Dietary
Exposure
and
Risk
for
Hexazinone
Population
of
Concern
Dietary
Exposure
(mg/
kg
bw/
day)
%
aPAD
Females
13
50
years
of
age
0.003611
<1.0
4.2.3
Chronic
Dietary
Exposure
Chronic
dietary
(food)
risk
estimates
associated
with
the
use
of
hexazinone
do
not
exceed
the
Agency's
level
of
concern
(>
100%
cPAD)
for
any
population
subgroup,
including
the
most
highly
exposed
subgroup
children
1
6.
The
chronic
dietary
risk
for
children
ages
1
6
is
approximately
15%
of
the
chronic
population
adjusted
dose
(cPAD)
and
approximately
4%
for
the
general
population.
(J.
Punzi,
Acute
and
Chronic
Dietary
Exposure
Assessment
for
the
TRED,
July
30,
2002.)
A
tier
I
analysis
was
done
for
the
chronic
dietary
risk
assessment.
This
is
the
most
conservative
type
of
analysis
assuming
that
residues
on
foods
as
consumed
are
equal
to
the
tolerance
levels
and
that
100%
of
the
each
crop
is
treated.
Hexazinone
chronic
dietary
exposure
assessment
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(DEEM
TM
),
software
Version
7.76
which
incorporates
consumption
data
from
USDA's
Continuing
Survey
of
Food
Intake
by
Individuals
(CSFII),
1989
1992.
Consumption
data
are
averaged
for
the
entire
U.
S.
population
and
within
population
subgroups
for
chronic
dietary
exposure
assessment.
For
chronic
exposure
and
risk
assessment,
an
estimate
of
the
residue
level
in
each
food
or
food
form
(e.
g.,
orange
or
orange
juice)
on
the
commodity
residue
list
is
multiplied
by
the
average
daily
consumption
estimate
for
that
food/
food
form.
The
resulting
residue
consumption
estimate
for
each
food/
food
form
is
summed
with
the
residue
consumption
estimates
for
all
other
food/
food
forms
to
arrive
at
the
total
estimated
exposure.
Chronic
population
adjusted
dose
(cPAD)
is
the
chronic
RfD
divided
by
the
FQPA
safety
factor.
The
calculated
chronic
exposure
(residue
x
consumption)
was
compared
to
a
cPAD
of
0.05
mg/
kg/
day,
which
reflects
a
special
FQPA
factor
of
1x
for
hazard
and
exposure.
The
procedure
is
performed
for
each
population
subgroup.
Results
of
this
chronic
dietary
exposure
and
risk
assessment
are
shown
in
Table
6.
30
Table
6:
Summary
of
Chronic
Dietary
Exposure
and
Risk
Values
for
Hexazinone
Population
Subgroup
Dietary
Exposure
(Mg/
kg/
day
%
cPAD
U.
S.
Population
0.002167
4
All
Infants
(<
1
year)
0.003752
7
Children
1
6
years
0.007449
15
Children
7
12
years
0.003964
8
Females
13
50
years
0.001308
3
Males
13
19
years
0.002334
5
Males
20+
years
0.001208
2
Seniors
55+
years
0.001159
2
HED
notes
that
there
is
a
degree
of
uncertainty
in
extrapolating
exposures
for
certain
population
subgroups
which
may
not
be
sufficiently
represented
in
the
consumption
surveys,
(e.
g.,
nursing
and
non
nursing
infants
or
Hispanic
females).
Therefore,
risk
estimates
provided
include
only
representative
sub
populations
that
have
sufficient
numbers
of
survey
respondents
(e.
g.,
all
infants,
or
females
13
50
years
of
age).
31
4.3
Water
Exposure/
Risk
Pathway
Environmental
fate
data
suggest
that
the
parent
and
degradates
are
likely
to
be
persistent
and
mobile
in
the
environment.
Leaching
and
runoff
are
expected
to
be
primary
dissipation
routes.
Metabolites
A,
B,
D,
1
(JS472),
and
2
(JT677)
are
major
metabolites
found
in
soil/
aquatic
studies.
Metabolites
A
1,
C
and
G3170
are
detected
in
ground
water
analysis.
Due
to
lack
of
toxicity
data
for
these
metabolites,
MARC
assumes
they
have
similar
toxicity
as
the
parent
because
of
the
structure
similarities
(except
G3170).
Metabolite
G3170
was
detected
at
the
highest
level
in
the
California
prospective
groundwater
study
(PGW)
and
there
are
no
toxicity
information
available
to
indicated
that
it
is
of
less
toxicological
concern
than
the
parent.
Therefore,
MARC
concludes
that
parent,
G3170,
and
all
degradates
with
conjoined
cyclohexyl
and
triazine
rings
(specifically,
A,
A
1,
B,
C,
D,
1
(JS472),
and
2
(JT677))
are
residues
of
concern
for
risk
assessment
in
water.
(S.
Kinard,
The
Outcome
of
the
HED
Metabolism
Assessment
Review
Committee
for
Water,
April
25,
2002.)
Drinking
water
degradates
A,
A
1,
B,
C
and
D
are
shown
in
Table
4;
degradates
G3170,
1,
and
2
are
shown
in
Table
7
below.
32
N
N
N
O
O
H
C
H
3
N
(CH
3
)
2
N
N
N
O
O
CH
3
N(
CH
3
)
2
O
N
N
N
O
N
CH
3
O
CH
3
CH
3
O
Table
7:
Drinking
Water
Degradates
Common
Name
Chemical
Name
Structure
Metabolites
G3170
6(
methylamino)
1
methyl
1,3,5
triazine
2,4
(1H,
3H)
dione
Metabolite
1,
JS472
3(
4
ketocyclohexyl)
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
Metabolite
2,
JT677
3(
2
ketocyclohexyl)
6(
dimethylamino)
1
methyl
1,3,5
triazine
2,4(
1H,
3H)
dione
The
environmental
fate
data
suggest
that
the
parent
and
degradates
are
likely
to
be
persistent
and
mobile
in
the
environment.
Leaching
and
runoff
are
expected
to
be
primary
dissipation
routes.
Estimated
Environmental
Concentrations
(EECs)
in
surface
waters
were
estimated
using
the
Tier
I
model
FIRST.
The
EECs
in
groundwater
were
estimated
using
an
available
small
scale
prospective
groundwater
monitoring
study.
In
addition,
there
are
monitoring
data
available
from
the
state
of
Maine,
but
these
data
are
used
for
comparison
purposes
only.
The
surface
water
concentrations,
for
hexazinone
residues
were
as
follows:
acute
(peak)
33
value,
130
ppb,
and
the
chronic
annual
average
value,
47
ppb,
based
on
the
application
of
hexazinone
on
alfalfa,
which
is
the
major
food/
feed
use
for
the
chemical.
These
values
represent
upper
bound
estimates
of
the
concentrations
that
might
be
found
in
surface
water
due
to
the
use
of
hexazinone
on
a
representative
crop.
The
groundwater
screening
concentration
for
hexazinone
residues
is
41.8
ppb.
It
is
noted
that
the
groundwater
screening
concentration
for
hexazinone
residues,
based
on
the
groundwater
prospective
monitoring
study
is
of
the
same
order
of
magnitude
of
the
groundwater
concentration
estimated
from
the
Tier
I
model
SCIGROW
(i.
e.,
20.2
ppb).
(Tier
I
Estimated
Environmental
Concentrations
of
Hexazinone
for
Use
in
the
Human
Health
Risk
Assessment,
D215026,
May
2,
2002.)
4.3.1
Environmental
Fate
Based
on
the
available
information,
hexazinone
appears
to
be
persistent
and
mobile
in
soil
and
aquatic
environments.
Hexazinone
is
stable
to
hydrolysis
(pH
levels
5,7,
and
9)
and
stable
to
aqueous
photolysis
(pH
7).
Studies
of
the
chemical's
half
life
in
aerobic
and
anaerobic
soil
and
aquatic
environments
show
that
hexazinone
half
life
in
the
environment
range
from
60
230
days.
Data
on
hexazinone
metabolites
of
concern
indicate
that
they
are
highly
mobile
in
the
environment.
Based
on
the
environmental
fate
properties
of
hexazinone
and
its
degradates,
it
can
be
concluded
they
may
be
of
concern
for
surface
water
and
groundwater
contamination.
Hexazinone
is
not
to
be
applied
under
the
following
conditions
to
limit
the
migration
of
hexazinone
to
drinking
water:
(1)
when
rainfall
is
expected
immediately
after
application;
(2)
to
the
field
where
the
water
table
is
shallow
or
the
water
body
is
nearby;
and
(3)
to
soils
containing
low
organic
matter
and/
or
high
sand
content.
Hexazinone
possesses
high
solubility
in
water
and
a
low
adsorption
coefficient
in
soil.
Therefore,
this
chemical
is
expected
to
be
very
mobile
in
the
environment,
especially
in
soils
with
low
organic
matter
and/
or
high
sand
content.
Results
from
aquatic
metabolism
studies
suggest
that
the
parent
compound
is
expected
to
be
relatively
persistent
when
it
reaches
surface
water.
Although
some
degradation
could
occur
in
the
surface
water,
the
chemical
structures
and
the
fate
properties
of
the
resulting
degradates
are
similar
to
the
parent.
According
to
the
aerobic
soil
metabolism,
19%
and
11%
of
the
applied
were
found
as
Degradates
A
1
and
1,
respectively,
after
one
year
of
incubation.
Hexazinone
can
be
applied
aerially
and,
therefore,
there
is
a
potential
for
runoff
from
spray
drift.
Hexazinone
is
expected
to
be
less
persistent
in
the
upper
layer
of
the
water
body
than
the
deep
layer.
The
bioconcentration
potential
is
very
low
for
this
chemical.
There
is
no
Safe
Drinking
Water
Act
Maximum
Contaminate
Level
(MCL)
for
the
chemical.
There
are
many
degradates
included
in
the
hexazinone
drinking
water
exposure
assessment.
They
include
degradates
G3170,
A,
A
1,
B,
C,
D,
1(
JS472),
2(
JT677).
It
is
noted
that
although
Degradate
C
was
not
found
in
any
of
the
laboratory
fate
studies,
the
field
dissipation
and
the
small
scale
prospective
groundwater
monitoring
study
observed
this
degradate.
In
addition,
degradates
D
and
2
were
the
major
degradates
found
in
the
anaerobic
34
aquatic
metabolism
study;
however,
the
field
dissipation
and
the
small
scale
prospective
groundwater
monitoring
studies
did
not
monitor
these
two
degradates.
Therefore,
the
fate
of
degradates
D
and
2
could
not
be
assessed
in
the
natural
environment.
The
registrant
believed
that
both
field
studies
were
mostly
aerobic
and
the
degradates
were
unlikely
to
be
observed.
The
field
dissipation
studies
did
not
monitor
the
fate
of
degradate
G
3170,
which
was
the
degradate
detected
at
the
highest
concentrations
in
the
small
scale
prospective
groundwater
monitoring
study.
This
degradate
was
not
observed
in
the
aerobic
soil
metabolism
study.
4.3.2
Drinking
Water
Exposure
Estimates
The
Agency
currently
lacks
sufficient
water
related
exposure
data
from
monitoring
to
complete
a
quantitative
drinking
water
exposure
analysis
and
risk
assessment
for
hexazinone
and
its
degradates.
The
Agency
is
presently
relying
on
a
computer
model,
FIRST,
to
estimate
the
environmental
concentrations
(EECs)
in
surface
water.
This
model
takes
into
account
the
use
patterns
and
the
environmental
profile
of
the
pesticide,
but
does
not
include
consideration
of
the
impact
that
processing
raw
water
for
distribution
as
drinking
water
could
have
on
the
removal
or
metabolism
of
pesticides
from
the
source
water.
The
registrant
submitted
a
small
scale
prospective
groundwater
monitoring
study
and
the
results
indicate
that
hexazinone
and
its
metabolites
are
very
mobile
and
persistent
in
the
environment.
The
results
of
this
monitoring
study
are
used
to
estimate
concentrations
of
hexazinone
and
its
degradates
in
groundwater.
The
State
of
Maine
Board
of
Pesticides
Control
in
the
Department
of
Agriculture,
Food
and
Rural
Resources
performed
a
statewide
assessment
to
determine
the
impact
of
highly
leachable
pesticides
including
hexazinone.
This
study
is
considered
informative
but
not
used
to
derive
estimated
environmental
concentrations
for
drinking
water
exposure
and
risk
assessment.
The
estimated
environmental
concentrations
of
hexazinone
and
degradates
in
groundwater
are
based
upon
the
prospective
groundwater
monitoring
study.
Surface
Water
The
FIRST
model
is
a
new
screening
model
designed
to
estimate
the
pesticide
concentrations
found
in
water
for
use
in
drinking
water
assessments.
The
model
provides
highend
values
on
the
concentrations
that
might
be
found
in
a
small
drinking
water
reservoir
due
to
the
use
of
pesticide.
Similar
to
GENEEC,
the
model
previously
used
for
Tier
I
screening
level,
FIRST
is
a
single
event
model
(one
run
off
event),
but
can
account
for
spray
drift
from
multiple
applications.
FIRST
uses
a
drinking
water
reservoir
instead
of
a
pond
as
the
standard
scenario.
The
FIRST
scenario
includes
a
427
acres
field
immediately
adjacent
to
a
13
acres
reservoir,
9
feet
deep,
with
continuous
flow
(two
turnovers
per
year).
The
pond
receives
a
spray
drift
event
from
each
application,
plus
one
runoff
event.
The
runoff
event
moves
a
maximum
of
8%
of
the
applied
pesticide
into
the
pond.
This
amount
can
be
reduced
due
to
degradation
on
field
and
the
effect
of
binding
to
soil.
Spray
drift
is
equal
to
6.4%
of
the
applied
concentration
from
the
35
ground
spray
application
and
16%
for
aerial
applications.
Model
inputs
used
to
develop
the
surface
water
estimated
environmental
concentrations
using
the
FIRST
model
include
estimating
drinking
water
exposure
based
on
application
to
alfalfa,
the
food/
feed
item
with
the
greatest
percent
of
crop
treated
with
hexazinone.
In
addition,
the
model
assumes
aerial
application,
an
application
rate
of
1.5
lbs.
a.
i./
acre,
application
once
per
year,
and
no
soil
incorporation
after
application.
FIRST
also
makes
adjustments
for
the
percent
of
the
area
cropped.
While
FIRST
assumes
that
the
entire
watershed
would
not
be
treated,
the
use
of
a
PCA
is
still
a
screen
because
it
represents
the
highest
percentage
of
crop
cover
of
any
large
watershed
in
the
US,
and
it
assumes
that
the
entire
crop
is
being
treated.
Other
conservative
assumptions
of
FIRST
include
the
use
of
a
small
drinking
water
reservoir
surrounded
by
a
runoff
prone
watershed,
the
use
of
the
maximum
use
rate,
assumption
of
no
buffer
zone,
and
a
single
large
rainfall.
Groundwater
The
registrant
submitted
a
small
scale
prospective
groundwater
monitoring
study
for
hexazinone
(MRID45132801).
In
this
study,
hexazinone
was
broadcast
applied
once
at
0.75
lb
a.
i./
A
in
January
1996
onto
a
field
of
alfalfa
underlain
with
sandy
soil
in
Merced
County,
California.
Results
indicated
that
hexazinone
and
its
degradates
are
very
mobile
and
persistent.
As
indicated
earlier,
the
degradates
D
and
2
(which
were
the
major
degradates
found
in
the
anaerobic
aquatic
metabolism
study),
were
not
monitored
in
the
small
scale
prospective
groundwater
monitoring
studies.
No
information
about
the
fate
of
degradates
D
and
2
under
natural
environment
is
currently
available.
Table
8
provides
a
summary
with
the
maximum
concentrations
of
the
parent
and
its
degradates,
detected
in
the
small
scale
prospective
groundwater
monitoring
study.
These
concentrations
(see
column
2)
were
expressed
in
parent
equivalents
(see
Column
3).
The
maximum
total
residues
of
hexazinone
and
its
degradates
detected
in
the
groundwater
study
were
41.8
ppb
(expressed
as
parent
equivalents).
36
Table
8:
Summary
of
Small
Scale
Prospective
Groundwater
Monitoring
Study
Chemical
Maximum
Concentration
in
Groundwater
(ppb)
Maximum
Concentration
in
Groundwater
(ppb,
expressed
as
parent
equivalent)
Parent
9.2
9.2
A
1
(G3453)
3
2.8
B
(A3928)
7.2
7.6
C
(T3935)
1.2
1.1
1
((
JS472)
2.1
2.0
G3170
12.9
19.1
Total
Residues
(parent
equivalent)
Not
applicable
41.8
The
State
of
Maine
also
conducted
a
drinking
water
monitoring
study,
however
these
data
are
considered
for
informational
purposes
only
and
are
presented
here
as
a
point
of
comparison.
The
Board
of
Pesticides
Control
in
the
Department
of
Agriculture,
Food
and
Rural
Resources
in
the
State
of
Maine
conducted
a
statewide
assessment
to
determine
the
impact
of
highly
leachable
pesticides
(including
hexazinone,
an
herbicide
used
in
the
production
of
blueberries)
on
surface
water
and
ground
water
in
Maine.
This
assessment
crossed
a
variety
of
agricultural
and
nonagricultural
pesticide
use
sites.
Surface
water
samples
were
collected
in
Narraguagus
River
and
Pleasant
River
in
Maine.
Although
the
total
amounts
of
hexazinone
used
on
blueberry
in
Maine
is
very
low
(only
approximately
1%
of
the
total
sale
in
the
U.
S.),
the
chemical
was
detected
in
groundwater
and
surface
water
at
very
high
frequency
(43
59%
of
ground
water
samples,
and
31
90%
of
surface
water
samples).
Although
this
monitoring
study
is
inherently
different
than
the
ground
water
prospective
monitoring
study,
it
was
observed
that
the
maximum
concentrations
of
parent
hexazinone
observed
in
groundwater
in
1998
and
1999
(i.
e.
2.15
and
1.97
ppb,
respectively),
were
similar
to
the
maximum
concentration
observed
in
the
small
scale
ground
water
monitoring
study
(i.
e.,
9.2
ppb).
Results
are
summarized
in
Table
9.
37
Table
9:
Summary
of
Monitoring
Information
from
the
Board
of
Pesticides
Control
in
the
Department
of
Agriculture,
Food
and
Rural
Resources
in
the
State
of
Maine
Year
No.
of
Samples
Collected
No.
of
Samples
with
Hexazinone
Detected
(%
of
Frequency)
Range
of
Concentrations
(ppb)
Ground
Water
1998
42
18
(43%)
0.14
2.15
1999
22
13
(59%)
0.22
1.97
Surface
Water
1998
36
11
(31%)
0.22
0.94
1999
21
19
(90%)
0.13
3.80
2000
24
21
(88%)
0.13
2.65
2001
50
44
(88%)
0.08
2.45
Therefore,
estimated
environment
concentrations
in
surface
and
groundwater
were
derived
from
both
modeled
data
and
a
prospective
groundwater
monitoring
study.
Aggregate
exposure
and
risks
from
consumption
of
hexazinone
contaminated
surface
water
as
drinking
water
will
utilize
the
FIRST
peak
untreated
water
concentration
of
129.8
ppb
for
the
acute
scenario
and
the
annual
average
untreated
water
concentration
of
47.1
ppb
for
the
chronic
scenario.
The
FIRST
model
estimates
include
all
drinking
water
degradates
of
concern
in
the
risk
assessment
(calculated
as
hexazinone
parent
equivalents).
Aggregate
exposure
and
risk
from
consumption
of
hexazinone
contaminated
groundwater
as
drinking
water
will
use
the
results
of
the
prospective
groundwater
monitoring
study,
41.8
ppb.
Although
this
study
did
not
monitor
for
the
presence
of
degradates
D
and
2,
it
is
still
considered
to
be
a
conservative
estimate
of
groundwater
drinking
water
exposure
since
the
total
residues
detected
in
this
study
are
twice
the
residue
level
estimated
through
the
SCI
GROW
model,
which
included
all
metabolites
in
the
model
estimate.
The
surface
and
groundwater
drinking
water
estimated
environmental
concentrations
are
listed
in
Table
10.
38
Table
10:
Estimated
Environmental
Concentrations
in
Surface
and
Groundwater
for
Hexazinone
use
on
Alfalfa
Model
Hexazinone
(Total
Residues)
Source
FIRST
1.0
Peak
Untreated
Water
Concentration
129.8
ppb
Output
FIRST
1.0
Annual
Average
Untreated
Water
Concentration
47.1
ppb
Output
Small
Scale
Prospective
Groundwater
Monitoring
Study
41.8
ppb
Monitoring
Data
SCI
GROW
Ground
Water
Concentration
20.2
ppb
Output
4.4
Residential
Exposure/
Risk
Pathway
There
are
currently
no
registered
uses
for
hexazinone
in
the
residential
environment.
However,
the
hexazinone
label
does
include
use
of
the
chemical
in
rights
of
way
areas
and
spray
drift
is
always
a
potential
source
of
exposure
to
residents
nearby
to
this
type
of
spraying
operation.
This
is
particularly
the
case
with
aerial
application,
but,
to
a
lesser
extent,
could
also
be
a
potential
source
of
exposure
from
groundboom
application
methods.
The
Agency
has
been
working
with
the
Spray
Drift
Task
Force,
EPA
Regional
Offices
and
State
Lead
Agencies
for
pesticide
regulation
and
other
parties
to
develop
the
best
spray
drift
management
practices.
The
Agency
is
now
requiring
interim
mitigation
measures
for
aerial
applications
that
must
be
placed
on
product
labels/
labeling.
The
Agency
has
completed
its
evaluation
of
the
new
data
base
submitted
by
the
Spray
Drift
Task
Force,
a
membership
of
U.
S.
pesticide
registrants,
and
is
developing
a
policy
on
how
to
appropriately
apply
the
data
and
the
AgDRIFT
computer
model
to
its
risk
assessments
for
pesticides
applied
by
air,
orchard
airblast
and
ground
hydraulic
methods.
After
the
policy
is
in
place,
the
Agency
may
impose
further
refinements
in
spray
drift
management
practices
to
reduce
off
target
drift
and
risks
associated
with
the
application
of
hexazinone
by
aerial
as
well
as
other
application
types
where
appropriate.
4.4.1
Other
Non
Occupational
Exposures
It
is
important
to
note
that
U.
S.
EPA,
Region
IX
is
working
with
the
California
Department
of
Pesticide
Regulation,
the
US
Forest
Service
and
Native
American
tribes
in
California
to
determine
the
potential
exposure
to
forestry
herbicides,
including
hexazinone,
that
may
be
occurring
to
Native
Americans
through
their
use
of
forest
plant
materials.
Native
Americans
use
these
plant
materials
in
their
diets,
in
the
making
of
traditional
basketry,
for
medicinal
purposes,
and
in
ceremonial
activities.
In
response
to
the
health
concerns
raised
by
the
Native
American
communities,
the
California
Department
of
Pesticide
Regulation
(DPR)
and
the
USEPA
(Region
IX)
launched
a
risk
assessment
effort
in
1997.
This
effort
includes
five
steps:
39
DPR
measured
plant
residue
and
surface
water
levels
following
herbicide
application;
DPR
agreed
to
assess
the
total
exposures
and
risks
involved
using,
where
appropriate,
the
monitoring
data
collected;
informing
tribal
physicians
of
state
regulations
requiring
pesticide
illness
reporting;
participation
in
mediated
meetings
with
Native
American
communities
to
determine
the
key
issues
surrounding
herbicide
use;
and,
video
production
about
inadvertent
exposure
to
herbicides.
The
Office
of
Pesticide
Programs
is
aware
of
this
ongoing
work
and
will
communicate
with
USEPA
Region
IX,
California
DPR
and
other
entities,
as
appropriate,
to
ensure
that
potential
exposures
and
risks
are
assessed.
5.0
Aggregate
Risk
Assessment
and
Characterization
The
Food
Quality
Protection
Act
(FQPA)
amendments
to
the
Federal
Food,
Drug,
and
Cosmetic
Act
(FFDCA)
requires
for
establishing
or
reassessing
a
pesticide
tolerance
"that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
the
pesticide
chemical
residue,
including
all
anticipated
dietary
exposures
and
all
other
exposure
for
which
there
is
reliable
information."
The
July
30,
3003
HIARC
meeting
resulted
in
endpoint
selection
for
multiple
exposure
durations
and
routes,
including
the
residential
pathway.
However,
exposure
is
only
expected
to
occur
via
the
food
and
water
pathways
of
exposure.
If
new
uses
are
added
to
the
label
in
the
future
which
include
possible
exposure
to
persons
in
the
residential
environment,
EPA
will
conduct
this
analysis.
The
toxicological
endpoints
appropriate
for
the
dietary
(oral)
route
of
exposure
are,
therefore,
the
only
hazard
endpoints
considered
in
this
analysis.
Acute
and
chronic
aggregate
risk
is
comprised
of
the
combined
exposures
from
food
and
water.
Risk
estimates
are
aggregated
because
it
is
assumed
exposure
may
occur
over
the
same
time
period
to
the
same
person.
The
HIARC
selected
an
acute
dietary
endpoint
for
females
13
50
based
upon
decreased
male
and
female
fetal
weight,
kidneys
with
no
papilla
(malformation)
and
misaligned
sternebrae
(variation)
at
the
LOAEL
in
the
developmental
rat
study.
However,
no
appropriate
effect
attributed
to
a
single
exposure
was
identified
in
the
toxicology
database
for
the
general
population.
The
chronic
dietary
aggregate
assessment
utilizes
an
endpoint
based
on
a
chronic
oral
study
in
the
dog
which
demonstrated
severe
body
weight
decrement
and
clinical
chemistry
changes
including
elevated
aspartate
aminotransferase
and
alkaline
phosphatase
at
the
LOAEL.
Drinking
Water
Levels
of
Comparisons
(DWLOCs)
are
used
to
estimate
aggregate
risk
from
drinking
water
sources.
DWLOCs
are
theoretical
upper
limits
of
a
pesticide's
allowable
concentration
in
drinking
water
in
light
of
total
aggregate
exposure
to
a
pesticide
in
food
and
drinking
water.
A
DWLOC
will
vary
depending
on
the
toxic
endpoint,
drinking
water
consumption,
and
body
weight.
The
Agency
uses
DWLOCs
internally
in
the
risk
assessment
process
as
a
surrogate
measure
of
potential
exposure
associated
with
pesticide
exposure
through
drinking
water.
In
the
absence
of
reliable
monitoring
data
for
pesticides
which
can
be
used
directly
and
quantitatively
in
the
risk
assessment,
it
is
used
as
a
point
of
comparison
against
conservative
model
estimates
of
a
pesticide's
concentration
in
water.
DWLOC
values
are
not
a
40
regulatory
standard
for
drinking
water.
However,
they
do
have
an
indirect
regulatory
impact
through
aggregate
exposure
and
risk
assessments.
For
this
analysis,
groundwater
monitoring
conclusions
are
used
to
compare
with
calculated
DWLOC
for
groundwater
and
modeling
results
are
used
to
compare
with
calculated
DWLOCs
in
surface
water.
Aggregate
risk
estimates
for
food
and
water
are
summarized
in
Tables
11
and
12.
The
estimates
of
food
exposure
are
considered
to
be
conservative
since
tolerance
level
residue
values
and
100%
of
crop
treatment
is
assumed.
5.1
Acute
Aggregate
Risk
Assessment
Since
the
calculated
EECs
are
less
than
the
DWLOC,
the
acute
aggregate
exposure
from
residues
of
hexazinone
and
its
metabolites
in
food
and
drinking
water
do
not
exceed
the
Agency's
level
of
concern.
HED
calculates
DWLOCs
by
a
two
step
process:
exposure
is
subtracted
from
the
aPAD
to
obtain
the
maximum
exposure
allowed
in
drinking
water;
DWLOCs
are
then
calculated
using
that
value
and
HED
default
body
weight
and
drinking
water
consumption
figures.
In
assessing
human
health
risk,
DWLOCs
are
compared
to
EECs.
When
EECs
are
less
than
DWLOCs,
HED
considers
the
aggregate
risk
[from
food
+
water
exposures]
to
be
acceptable.
Estimated
environmental
concentrations
for
hexazinone
and
its
water
degradates
were
compared
to
the
acute
DWLOCs
since
adequate
monitoring
data
were
not
available
to
directly
assess
aggregate
exposure
to
food
and
water.
The
Environmental
Fate
and
Effects
Division
(EFED)
provided
Tier
I
FIRST
estimates
to
determine
acute
dietary
aggregate
exposure
and
risk
values.
This
model
simulated
hexazinone
and
its
metabolites
in
drinking
water
concentrations
(for
the
alfalfa
use)
of
130
µg/
L
for
the
surface
water
peak
untreated
water
concentration.
The
results
of
the
Small
Scale
Prospective
Groundwater
Monitoring
Study
were
used
to
estimate
concentrations
of
hexazinone
and
its
degradates
in
groundwater
(42
µg/
L).
Interestingly,
the
results
of
the
monitoring
study
and
the
results
of
the
SCI
GROW
model
are
roughly
equivalent,
42
µg/
L
as
compared
to
20.2
µg/
L.
The
DWLOC
calculated
for
acute
aggregate
risk
for
females
13
50
years
old
is
120,000
µg/
L.
These
results
are
presented
in
Table
11.
Therefore,
HED
concludes
with
reasonable
certainty
that
residues
of
hexazinone
and
its
metabolites
in
drinking
water
will
not
contribute
significantly
to
the
acute
human
health
risk
and
that
the
acute
aggregate
exposure
from
residues
of
hexazinone
and
its
metabolites
in
food
and
drinking
water
and
will
not
exceed
the
Agency's
level
of
concern
for
acute
aggregate
exposure
for
females
13
50.
41
Table
11.
Acute
DWLOC
Calculation
Population
Subgroup
Acute
Scenario
aPAD
(mg/
kg/
day)
Acute
Food
Exposure
(mg/
kg/
day)
1
Max
Acute
Water
Exposure
(mg/
kg/
day)
2
Groundwater
EEC
(
:
g/
l)
3
Surface
Water
EEC
(
:
g/
l)
4
Acute
DWLOC
(
:
g/
l)
5
Females
13
50
4.0
0.003611
3.996
42
130
120,000
1
Acute
food
exposure
is
exposure
estimate
at
the
95th
percentile
from
the
Tier
I
assessment
performed.
2
Maximum
acute
water
exposure
(mg/
kg/
day)
=
[(
acute
PAD
(mg/
kg/
day)
acute
food
exposure
(mg/
kg/
day)]
3
Results
of
Small
Scale
Prospective
Groundwater
Monitoring
Study
are
used
for
groundwater
EEC.
4
The
crop
producing
the
highest
level
was
modeled
to
produce
the
surface
water
EEC
results,
alfalfa.
5
Acute
DWLOC(
µg/
L)
=
[maximum
acute
water
exposure
(mg/
kg/
day)
x
body
weight
(kg)]
[water
consumption
(L)
x
10
3
mg/
µg]
Assumptions:
Body
weights
(60
kg
adult
female);
water
consumption
2
liters/
day
adult.
5.2
Chronic
Aggregate
Risk
Assessment
Since
the
calculated
DWLOCs
are
above
the
drinking
water
exposure
estimates,
chronic
aggregate
exposure
from
residues
of
hexazinone
and
its
metabolites
in
food
and
drinking
water
sources
do
not
exceed
the
Agency's
level
of
concern
for
chronic
aggregate
exposure
for
any
subpopulation
EFED
provided
Tier
I
FIRST
estimates
to
determine
chronic
dietary
aggregate
exposure
and
risk
values.
This
model
simulated
drinking
water
concentrations
of
hexazinone
and
its
degradates
(for
the
alfalfa
use)
of
47
µg/
L
for
the
surface
water
annual
average
untreated
water
concentration.
The
results
of
a
Small
Scale
Prospective
Groundwater
monitoring
study
were
used
to
estimate
concentrations
of
hexazinone
in
groundwater
(42
µg/
L).
The
DWLOC
calculated
for
chronic
aggregate
risk
for
all
populations
range
from
425
1700
:
g/
L.
These
results
are
presented
in
Table
12.
Because
the
EECs
are
less
than
the
calculated
DWLOC,
HED
concludes
with
reasonable
certainty
that
residues
of
hexazinone
and
its
metabolites
in
drinking
water
will
not
contribute
significantly
to
the
chronic
human
health
risk
and
that
the
chronic
aggregate
exposure
from
residues
of
hexazinone
and
its
metabolites
in
food
and
drinking
water
and
will
not
exceed
the
Agency's
level
of
concern
for
chronic
aggregate
exposure
for
any
sub
population.
42
Table
12:
Chronic
DWLOC
Calculations
Population
Subgroup
1
Chronic
Scenario
cPAD
mg/
kg/
day
Chronic
Food
Exposure
mg/
kg/
day
Max
Chronic
Water
Exposure
mg/
kg/
day
2
Ground
Water
EEC
(µg/
L)
3
Surface
Water
EEC
(µg/
L)
3
Chronic
DWLOC
(µg/
L)
4
U.
S.
Population
0.05
0.002167
0.04783
42
47
1700
Females
13
50
0.05
0.001308
0.04869
42
47
1500
Infants
(<
1
year)
0.05
0.003752
0.04625
42
47
460
Children
1
6
0.05
0.007449
0.04255
42
47
425
1
Children
1
6
are
the
most
highly
exposed
sub
group.
2
Maximum
Chronic
Water
Exposure
(mg/
kg/
day)
=
[Chronic
PAD
(mg/
kg/
day)
Chronic
Dietary
Exposure
(mg/
kg/
day)]
3
The
use
of
hexazinone
on
alfalfa
was
modeled
to
determine
surface
water
EEC's
and
the
results
of
groundwater
monitoring
study
was
used
to
determined
groundwater
EEC.
4
Chronic
DWLOC(
µg/
L)
=
[maximum
chronic
water
exposure
(mg/
kg/
day)
x
body
weight
(kg)]
[water
consumption
(L)
x
10
3
mg/
µg]
Assumptions:
Body
weights
(70
kg
adult
male;
60
kg
adult
female;
10
kg
child);
water
consumption
2
liters/
day
adult
and
1
liter/
day
infants
and
children.
6.0
Cumulative
Risk
The
FQPA
(1996)
stipulates
that
when
determining
the
safety
of
a
pesticide
chemical,
EPA
shall
base
its
assessment
of
the
risk
posed
by
the
chemical
on,
among
other
things,
available
information
concerning
the
cumulative
effects
to
human
health
that
may
result
from
dietary,
residential,
or
other
non
occupational
exposure
to
other
substances
that
have
a
common
mechanism
of
toxicity.
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
A
person
exposed
to
a
pesticide
at
a
level
that
is
considered
safe
may
in
fact
experience
harm
if
that
person
is
also
exposed
to
other
substances
that
cause
a
common
toxic
effect
by
a
mechanism
common
with
that
of
the
subject
43
pesticide,
even
if
the
individual
exposure
levels
to
the
other
substances
are
also
considered
safe.
HED
did
not
perform
a
cumulative
risk
assessment
as
part
of
the
TRED
for
hexazinone
because
HED
has
not
yet
initiated
a
comprehensive
review
to
determine
if
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
hexazinone.
For
purposes
of
this
TRED,
the
Agency
has
assumed
that
hexazinone
does
not
have
a
common
mechanism
of
toxicity
with
other
substances.
On
this
basis,
the
registrant
must
submit,
upon
EPA's
request
and
according
to
a
schedule
determined
by
the
Agency,
such
information
as
the
Agency
directs
to
be
submitted
in
order
to
evaluate
issues
related
to
whether
hexazinone
shares
a
common
mechanism
of
toxicity
with
any
other
substance
and,
if
so,
whether
any
tolerances
for
hexazinone
need
to
be
modified
or
revoked.
If
HED
identifies
other
substances
that
share
a
common
mechanism
of
toxicity
with
hexazinone,
HED
will
perform
aggregate
exposure
assessments
on
each
chemical,
and
will
begin
to
conduct
a
cumulative
risk
assessment.
HED
has
developed
a
framework
for
conducting
cumulative
risk
assessments
on
substances
that
have
a
common
mechanism
of
toxicity.
This
guidance
was
issued
on
January
16,
2002
(67
FR
2210
2214)
and
is
available
from
the
OPP
Website
at:
http://
www.
epa.
gov/
pesticides/
trac/
science/
cumulative_
guidance.
pdf.
Before
undertaking
a
cumulative
risk
assessment,
HED
will
follow
procedures
for
identifying
chemicals
that
have
a
common
mechanism
of
toxicity
as
set
forth
in
the
"Guidance
for
Identifying
Pesticide
Chemicals
and
Other
Substances
that
Have
a
Common
Mechanism
of
Toxicity"
(64
FR
5795
5796,
February
5,
1999).
7.0
Incident
Data
The
Agency
searched
several
databases
for
reports
of
poisoning
incident
data
for
hexazinone.
These
databases
include
the
Office
of
Pesticide
Programs
(OPP)
Incident
Data
System
(IDS),
the
Poison
Control
Center
data,
California
Department
of
Pesticide
Regulation,
and
the
National
Pesticide
Telecommunication
Network
(NPTN).
Relatively
few
incidents
have
been
reported.
Cases
listed
in
the
IDS
include
individuals
reporting
burning
and
red
welts
on
the
legs,
eye
irritation
and
peeling
on
their
hands
and
feet.
Other
databases
included
reports
of
eye
effects
and
breathing
difficulties
after
exposure.
Because
there
are
so
few
cases
available,
no
recommendations
can
be
made
based
on
the
few
incident
reports
available.
(J.
Blondell,
Review
of
Hexazinone
Incident
Reports,
May
1,
2002.)
44
8.0
Data
Needs
Product
Chemistry
1.
The
product
chemistry
data
base
is
complete.
Toxicology
2.
The
HIARC
requested
a
28
day
inhalation
study
on
formulation
with
hexazinone
because
of
the
concern
for
potential
inhalation
exposure
based
on
the
use
pattern.
Residue
Chemistry
3.
Outstanding
label
amendments
to
reflect
cancellation
of
use
on
pasture/
rangeland
grasses.
4.
Field
rotational
crop
studies
for
corn
and
wheat.
Environmental
Fate
5.
The
environmental
fate
database
is
complete.
45
References
Anderson,
D.
Hexazinone
(PC
Code
107201).
Toxicology
Disciplinary
Chapter
for
the
Tolerance
Reassessment
Eligibility
Decision
Document.
August
12,
2002.
TXR
No.
0051040.
DP
Barcode
D275620.
Anderson,
D.
Hexazinone
3rd
Report
of
the
Hazard
Identification
Assessment
Review
Committee.
August
12,
2002.
TXR
No.
0051003.
Blondell,
J.
and
M.
Spann.
Review
of
Hexazinone
Incident
Reports.
Chemical
107201.
May
1,
2002.
Dockter,
K.
Hexazinone.
Product
Chemistry
Chapter
for
the
Tolerance
Reassessment
Eligibility
Decision
(TRED)
Document.
April
23,
2002.
DP
Barcode
D279324.
Hernandez,
F.
Quantitative
Usage
Analysis
for
Hexazinone.
September
10,
2001.
Kinard,
S.
Hexazinone.
The
Outcome
of
the
HED
Metabolism
Assessment
Review
Committee
for
Water.
PC
code
107201,
April
25,
2002.
DP
Barcode
D282111.
Li,
L.
2002.
Data
Analysis
of
Forestry
Herbicides
in
Plants
of
Interest
of
California
Tribes.
Final
Report.
Retrieved
from
Http://
www.
cdpr.
ca.
gov/
docs/
empm/
pubs/
forest/
reprts.
htm.
Liu,
L.
Tier
I
Estimated
Environmental
Concentrations
of
Hexazinone,
for
use
in
Human
Health
Risk
Assessment
Water
Assessment.
Environmental
Fate
and
Effects
Division.
May
2,
2002.
Punzi,
J.
Hexazinone.
Acute
and
Chronic
Dietary
Exposure
Assessments
for
the
TRED.
(PC
Code
107201).
July
30,
2002.
DP
Barcode
D279898.
Punzi,
J.
Hexazinone
Tolerance
Reassessment
Eligibility
Decision
Residue
Chemistry
Considerations.
May
20,
2002.
(DP
Barcode
D279899).
Segawa,
R.,
C.
Ando,
A.
Bradley,
J.
Walters,
R.
Sava,
C.
Gana,
et
al.
(2001).
Dissipation
and
Off
site
Movement
of
Forestry
Herbicides
in
Plants
of
Importance
to
California
Tribes.
Final
Report.
Retrieved
from
Http://
www.
cdpr.
ca.
gov/
docs/
empm/
pubs/
forest/
reprts.
htm.
Tarplee,
B.
Hexazinone
2
nd
Report
of
the
FQPA
Safety
factor
Committee.
August
8,
2002.
TXR.
No.
0051049.
Commodity
Current
Tolerance
(ppm)
a
Range
of
residues
(ppm)
b
Tolerance
Reassessment
(ppm)
Comment/
Correct
Commodity
Definition
46
Blueberries
0.2
<0.3
ppm
(nondetectable;
<0.05
ppm
for
each
compound)
0.60
Tolerance
should
be
increased
based
on
the
combined
LOQ
(0.55
ppm)
of
the
enforcement
method.
Blueberry
Cattle,
fat
0.
1
Revoke
c
Cattle,
mbyp
0.1
0.
10
Cattle,
meat
0.1
0.
10
Goat,
fat
0.
1
Revoke
c
Goat,
mbyp
0.1
0.
10
Goats,
meat
0.1
0.
10
Grasses,
pasture
10
Revoke
d
Grass,
forage
Grass,
hay
Grasses,
rangeland
10
Revoke
d
Hog,
fat
0.
1
Revoke
c
Hog,
mbyp
0.1
Revoke
c
Hog,
meat
0.1
Revoke
c
Horses,
fat
0.
1
Revoke
c
Horses,
mbyp
0.1
0.
10
Horses,
meat
0.1
0.
10
Milk
0.5
0.
20
Pineapple
0.
5
<0.35
(or
<0.05
ppm
for
each
compound)
0.60
Tolerance
should
be
increased
based
on
the
combined
LOQ
(0.55
ppm)
of
the
enforcement
method.
Sheep,
fat
0.
1
Revoke
c
Sheep,
mbyp
0.1
0.
10
Sheep,
meat
0.1
0.
10
Tolerances
needed
under
40
CFR
§180.396(
a):
Alfalfa,
seed
<1.30<
1.46
2.
0
Table
C
(continued).
Commodity
Current
Tolerance
(ppm)
a
Range
of
residues
(ppm)
b
Tolerance
Reassessment
(ppm)
Comment/
Correct
Commodity
Definition
47
Tolerances
listed
under
40
CFR
§180.396(
c):
Sugarcane
0.
2
<0.05
ppm
(nondetectable)
each
for
hexazinone
and
its
metabolites
0.60
Tolerance
should
be
increased
based
on
the
combined
LOQ
(0.55
ppm)
of
the
enforcement
method.
Sugarcane
molasses
5
(1.915
x
4x)
÷
2x
=
3.83
4.0
a
Expressed
in
terms
of
the
combined
residues
of
hexazinone
and
its
metabolites
(calculated
as
hexazinone).
b
Refer
to
section
on
Magnitude
of
Residues
in
Crop
Plant
for
detailed
discussion
of
residues
in
crops.
c
Tolerances
for
fat
are
not
required
(Category
3,
40
CFR
§180.6).
d
HED
is
recommending
revocation
of
these
tolerances
and
cancellation
of
uses,
since
grasses
are
a
major
feed
item
and
required
data
are
not
available
for
reassessment.
| epa | 2024-06-07T20:31:42.983970 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0188-0027/content.txt"
} |
EPA-HQ-OPP-2002-0192-0001 | Notice | "2002-09-18T04:00:00" | Diquat Dibromide; Notice of Availability of Decision on Syngenta's Request to Modify Requirements and Closure of 1995 RED | 58797
Federal
Register
/
Vol.
67,
No.
181
/
Wednesday,
September
18,
2002
/
Notices
Screening
Program.
Chlorpropham
will
be
reevaluated
at
that
time
and
additional
studies
may
be
required.
Additionally,
the
Agency
has
evaluated
the
dietary
risk
associated
with
chlorpropham
and
has
determined
that
provided
the
Special
Local
Need
(
SLN)
registration
for
Easter
lily
bulb
use
is
amended
to
reduce
the
maximum
rate
of
application
from
3.99
pounds
active
ingredient/
acre
to
2.0
pounds
active
ingredient/
acre,
as
agreed
upon
by
stakeholders,
there
is
a
reasonable
certainty
that
no
harm
to
any
population
subgroup
will
result
from
aggregate
exposure
to
chlorpropham
when
considering
dietary
exposure
and
all
other
non
occupational
sources
of
pesticide
exposure
for
which
there
is
reliable
information.
Therefore,
with
this
mitigation
measure
in
place,
15
tolerances
are
now
considered
reassessed
and
9
new
tolerances
will
be
established
for
residues
of
chlorpropham
in/
on
raw
agricultural
commodities
under
section
408(
q)
of
the
FFDCA.
All
registrants
of
pesticide
products
containing
the
active
ingredient
listed
in
this
document
have
been
sent
the
appropriate
TRED
document,
and
must
respond
to
labeling
requirements
within
8
months
of
receipt.
In
addition,
the
Agency
requests
a
response
to
the
generic
Data
Call
In
(
DCI)
letter
from
technical
registrants
within
90
days
of
receipt.
The
reregistration
program
is
being
conducted
under
Congressionallymandated
time
frames,
and
EPA
recognizes
both
the
need
to
make
timely
reregistration
decisions
and
to
involve
the
public.
All
comments
received
within
30
days
of
publication
of
this
Federal
Register
notice
will
be
considered
by
the
Agency.
If
any
comment
significantly
impacts
this
TRED,
the
Agency
will
amend
its
decision
by
publishing
a
Federal
Register
notice.
B.
What
is
the
Agency's
Authority
for
Taking
this
Action?
The
legal
authority
for
this
TRED
falls
under
FIFRA,
as
amended
in
1988
and
1996.
Section
4(
g)(
2)(
A)
of
FIFRA
directs
that,
after
submission
of
all
data
concerning
a
pesticide
active
ingredient,
``
the
Administrator
shall
determine
whether
pesticides
containing
such
active
ingredient
are
eligible
for
reregistration,''
and
either
reregistering
products
or
taking
``
other
appropriate
regulatory
action.''
List
of
Subjects
Environmental
protection,
Pesticides,
Tolerances.
Dated:
September
10,
2002.
Lois
A.
Rossi,
Director,
Special
Review
and
Reregistration
Division,
Office
of
Pesticide
Programs.
[
FR
Doc.
02
23593
Filed
9
17
02;
8:
45
am]
BILLING
CODE
6560
50
S
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
2002
0192;
FRL
7197
9]
Diquat
Dibromide;
Notice
of
Availability
of
Decision
on
Syngenta's
Request
to
Modify
Label
Requirements
and
Closure
of
1995
RED
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.
SUMMARY:
This
notice
announces
EPA's
intention
to
modify
certain
occupational
and
residential
risk
mitigation
measures
that
were
imposed
as
a
result
of
the
1995
Reregistration
Eligibility
Decision
(
RED)
for
diquat
dibromide.
At
the
end
of
the
comment
period,
the
Agency
will
consider
this
action
an
immediate
final
decision
and
the
1995
RED
closed,
unless
adverse
comments
are
received.
The
Agency
conducted
this
reassessment
in
response
to
new
data
submitted
by
the
technical
registrant,
Syngenta
Crop
Protection,
Inc.
Syngenta
has
requested
the
Agency
modify
certain
diquat
dibromide
label
requirements
including:
Personal
protective
equipment
(
PPE),
closed
loading
system
for
aerial
applications,
reentry
intervals,
and
allow
residential
broadcast
spray
uses.
DATES:
Comments,
identified
by
docket
identification
(
ID)
number
OPP
2002
0192,
must
be
received
on
or
before
October
18,
2002.
ADDRESSES:
Comments
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP
2002
0192
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
Tyler
Lane,
Special
Review
and
Reregistration
Division
(
7508C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(
703)
305
2737;
email
address:
lane.
tyler@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
This
action
is
directed
to
the
public
in
general,
nevertheless,
a
wide
range
of
stakeholders
will
be
interested
in
obtaining
information
on
the
label
adjustments
for
diquat
dibromide,
including
environmental,
human
health,
and
agricultural
advocates;
the
chemical
industry;
pesticide
users;
and
members
of
the
public
interested
in
the
use
of
pesticides
on
food.
Since
other
entities
also
may
be
interested,
the
Agency
has
not
attempted
to
describe
all
the
specific
entities
that
may
be
affected
by
this
action.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
this
Document
and
Other
Related
Documents?
1.
Electronically.
You
may
obtain
electronic
copies
of
this
document,
and
certain
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
at
http://
www.
epa.
gov/.
On
the
Home
Page
select
``
Laws
and
Regulations,''
``
Regulations
and
Proposed
Rules,''
and
then
look
up
the
entry
for
this
document
under
the
``
Federal
Register
Environmental
Documents.''
You
can
also
go
directly
to
the
Federal
Register
listings
at
http://
www.
epa.
gov/
fedrgstr/.
Copies
of
the
tolerance
reassessment
decision
and
supporting
risk
assessment
documents
for
the
reregistration
of
diquat
dibromide
may
also
be
accessed
at
http:/
/
www.
epa.
gov/
pesticides/
reregistration/
diquat_
dibromide.
htm.
2.
In
person.
The
Agency
has
established
an
official
record
for
this
action
under
docket
ID
number
OPP
2002
0192.
The
official
record
consists
of
the
documents
specifically
referenced
in
this
action,
and
other
information
related
to
this
action,
including
any
information
claimed
as
Confidential
Business
Information
(
CBI).
This
official
record
includes
the
documents
that
are
physically
located
in
the
docket,
as
well
as
the
documents
that
are
referenced
in
those
documents.
The
public
version
of
the
official
record
does
not
include
any
information
claimed
as
CBI.
The
public
version
of
the
official
record
is
available
for
inspection
in
the
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(
703)
305
5805.
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Register
/
Vol.
67,
No.
181
/
Wednesday,
September
18,
2002
/
Notices
C.
How
and
to
Whom
Do
I
Submit
Comments?
You
may
submit
comments
through
the
mail,
in
person,
or
electronically.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP
2002
0192
in
the
subject
line
on
the
first
page
of
your
response.
1.
By
mail.
Submit
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Information
Resources
and
Services
Division
(
7502C),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460.
2.
In
person
or
by
courier.
Deliver
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Information
Resources
and
Services
Division
(
7502C),
Office
of
Pesticide
Programs
(
OPP),
Environmental
Protection
Agency,
Rm.
119,
Crystal
Mall
#
2,
1921
Jefferson
Davis
Highway,
Arlington,
VA.
The
PIRIB
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(
703)
305
5805.
3.
Electronically.
You
may
submit
your
comments
electronically
by
e
mail
to:
opp
docket@
epa.
gov,
or
you
can
submit
a
computer
disk
as
described
above.
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
Avoid
the
use
of
special
characters
and
any
form
of
encryption.
Electronic
submissions
will
be
accepted
in
WordPerfect
6.1/
8.0/
9.0
or
ASCII
file
format.
All
comments
in
electronic
form
must
be
identified
by
docket
ID
number
OPP
2002
0192.
Electronic
comments
may
also
be
filed
online
at
many
Federal
Depository
Libraries.
D.
How
Should
I
Handle
CBI
That
I
Want
to
Submit
to
the
Agency?
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
You
may
claim
information
that
you
submit
to
EPA
in
response
to
this
document
as
CBI
by
marking
any
part
or
all
of
that
information
as
CBI.
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
as
CBI
must
be
submitted
for
inclusion
in
the
public
version
of
the
official
record.
Information
not
marked
confidential
will
be
included
in
the
public
version
of
the
official
record
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
CBI,
please
consult
the
person
identified
under
FOR
FURTHER
INFORMATION
CONTACT.
E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?
You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
1.
Explain
your
views
as
clearly
as
possible.
2.
Describe
any
assumptions
that
you
used.
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
your
views.
4.
If
you
estimate
potential
burden
or
costs,
explain
how
you
arrived
at
the
estimate
that
you
provide.
5.
Provide
specific
examples
to
illustrate
your
concerns.
6.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
document.
7.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
ID
number
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
may
also
provide
the
name,
date,
and
Federal
Register
citation.
II.
Background
A.
What
Action
is
the
Agency
Taking?
In
1995,
the
Agency
published
its
Reregistration
Eligibility
Decision
(
RED)
for
diquat
dibromide.
Subsequent
to
the
publication
of
the
1995
RED,
the
technical
registrant
submitted
additional
data
to
further
refine
diquat
dibromide
worker
exposure
and
residential
broadcast
spray
use
scenarios.
Changes
to
the
PPE
label
requirements
of
the
1995
RED
are
based
on
the
submission
of
additional
data
from
a
biomonitoring
study
of
knapsack
applications
of
the
closely
related
chemical
paraquat,
and
a
reconsideration
of
the
acute
dermal
toxicity
endpoint.
The
Agency
reevaluated
the
dermal
toxicity
endpoint
and
rendered
a
decision
that
the
repeated
dose
dermal
toxicity
study
used
for
the
1995
RED
was
not
appropriate
for
use
in
the
risk
assessment
because
the
skins
of
the
rats
used
in
the
study
were
compromised.
Instead,
the
Agency
extrapolated
a
dermal
toxicity
endpoint
from
a
shortterm
oral
study
on
rabbits.
The
Agency
has
also
reevaluated
dermal
absorption
assumptions.
Previously,
EPA
assumed
a
standard
absorption
rate
of
4.1%,
based
on
a
rat
dermal
absorption
study.
Syngenta
cited
a
human
dermal
absorption
study
estimating
a
0.3%
dermal
absorption
rate
for
diquat
dibromide
(
Feldman
RJ
and
Maibach
HI,
``
Percutaneous
penetration
of
some
pesticides
and
herbicides
in
man''
Tox.
Appl.
Pharm.
28
126
132,
1974).
The
Agency
has
relied
on
data
provided
by
the
Feldman
Maibach
study
for
previous
risk
assessments,
and
believes
the
study
to
be
acceptable
and
the
data
valid
for
use
in
this
risk
assessment.
The
use
of
the
dermal
absorption
factor
of
0.3%
further
refines
all
aggregate
margins
of
exposure
(
MOEs)
above
the
target
MOE
of
100,
which
would
not
be
of
concern
to
the
Agency.
The
Agency
has
evaluated
the
request
to
modify
the
cited
label
requirements
and
summarized
its
assessment
in
the
Occupational
Risk
Evaluation:
``
Assessing
Syngenta's
Request
to
Modify
Diquat
Dibromide
Label
Requirements,''
dated
February
14,
2002.
In
addition,
the
``
HED
Risk
Assessment
for
Tolerance
Reassessment
Eligibility
Document
(
TRED),''
March
6,
2002,
and
the
``
Re
characterization
of
Risk
for
the
Diquat
Dibromide
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
Based
on
New
Dermal
Absorption
Data,''
March
13,
2002,
were
used
to
aid
in
the
assessment
of
aggregate
risks
from
residential
uses.
Any
labeling
changes
are
presented
in
the
``
Required
Labeling
Changes
Summary
Table,''
which
summarizes
the
labeling
requirements
for
this
action.
All
supporting
documents
referenced
in
this
document
are
available
in
the
public
docket
and
at
http://
www.
epa.
gov/
pesticides/
reregistration/
diquat_
dibromide.
htm.
In
summary,
the
Agency
expects
to
change
the
label
requirements
of
the
1995
RED
for
worker
PPE
and
residential
broadcast
spray
uses.
The
following
table
presents
the
1995
RED
decisions
being
reevaluated,
the
requests
to
change
these
requirements
made
by
Syngenta,
and
the
current
Agency
decisions
to
amend
the
1995
RED:
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Federal
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/
Vol.
67,
No.
181
/
Wednesday,
September
18,
2002
/
Notices
July
1995
RED
Syngenta
Request
Amendments
to
1995
RED
All
workers
required
to
wear
a
double
layer
of
clothing
(
coveralls
over
long
sleeved
shirt,
long
pants),
chemical
resistant
gloves,
chemical
resistant
footwear
plus
socks,
chemical
resistant
headgear
for
overhead
exposure,
and
a
chemical
resistant
apron
when
cleaning
equipment,
mixing
or
loading)
Reduced
PPE
requirements
due
potential
for
heat
stress
to
field
workers
and
applicators
All
workers
must
continue
to
wear
protective
footwear
and
coveralls
over
a
single
layer
of
clothes
(
products
with
a
dermal
toxicity
of
III
or
IV
may
reduce
PPE
to
protective
footwear
and
coveralls
over
short
pants
and
short
sleeve
shirts).
Mixers,
loaders
and
hand
applicators
must
wear
chemical
resistant
gloves,
while
applicators
who
are
operating
closed
cab
equipment
are
not
required
to
wear
chemical
resistant
gloves
due
to
MOEs
over
1,000.
Respirators
for
mixing
and
loading
No
respirator
requirements
for
mixing
and
loading
due
to
potential
for
heat
stress
Respirator
requirement
for
mixer/
loaders
reduced
to
a
face
shield
to
prevent
droplets
from
entering
the
eyes,
mouth
or
nose
areas
Closed
mixing
system
for
aerial
applications.
Open
mixing
system
for
aerial
applications
Closed
mixing/
loading
requirements
remain
for
aerial
applications
7
Day
restricted
entry
interval
(
REI)
for
products
used
under
the
Worker
Protection
Standard
(
WPS)
unless
there
is
no
contact
with
treated
surfaces
(
such
as
mechanical
harvesting)
4
Hour
REI
for
potato
desiccation
and
seed
crops
REI
reduced
to
24
hours
for
all
WPS
uses,
based
on
default
reentry
analysis
findings
of
MOEs
between
150
and
1,500
and
a
toxicity
category
II
for
eye
irritation
4
Day
REI
for
non
WPS
uses
other
than
aquatic
and
spot
treatment
at
residential
sites
REI
when
spray
is
dry
for
non
WPS
uses
REI
reduced
to
``
when
sprays
are
dry''
for
non
WPS
uses,
also
based
on
default
reentry
analysis
Prohibition
of
broadcast
spray
applications
for
homeowner
and
residential
uses
Broadcast
spray
applications
for
homeowner
and
residential
uses
Generic
data
requirements
have
been
fulfilled
for
residential
broadcast
spray
uses.
Broadcast
spray
applications
for
homeowner
and
residential
uses
for
enduse
products
will
be
decided
on
a
case
by
case
basis
upon
review
of
end
use
product
toxicity,
based
on
short
term
exposure
and
individual
risk
assessments.
B.
What
is
the
Agency's
Authority
for
Taking
this
Action?
The
legal
authority
for
this
decision
falls
under
FIFRA,
as
amended
in
1988
and
1996.
Section
4(
g)(
2)(
A)
of
FIFRA
directs
that,
after
submission
of
all
data
concerning
a
pesticide
active
ingredient,
``
the
Administrator
shall
determine
whether
pesticides
containing
such
active
ingredient
are
eligible
for
reregistration,''
and
either
reregister
products
or
take
other
``
appropriate
regulatory
action.''
List
of
Subjects
Environmental
protection,
Chemicals,
Aquatic
herbicides.
Dated:
September
5,
2002.
Lois
Rossi,
Director,
Special
Review
and
Reregistration
Division,
Office
of
Pesticide
Programs.
[
FR
Doc.
02
23594
Filed
9
17
02;
8:
45
am]
BILLING
CODE
6560
50
S
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
2002
0201;
FRL
7194
5]
Notice
of
Filing
a
Pesticide
Petition
to
Establish
a
Tolerance
for
a
Certain
Pesticide
Chemical
in
or
on
Food
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.
SUMMARY:
This
notice
announces
the
initial
filing
of
a
pesticide
petition
proposing
the
establishment
of
regulations
for
residues
of
a
certain
pesticide
chemical
in
or
on
various
food
commodities.
DATES:
Comments,
identified
by
docket
ID
number
OPP
2002
0201,
must
be
received
on
or
before
October
18,
2002.
ADDRESSES:
Comments
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
Unit
I.
C.
of
the
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP
2002
0201
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
By
mail:
Bipin
Gandhi,
Registration
Division
(
7505C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(
703)
308
8380;
e
mail
address:
gandhi.
bipin@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
You
may
be
affected
by
this
action
if
you
are
an
agricultural
producer,
food
manufacturer
or
pesticide
manufacturer.
Potentially
affected
categories
and
entities
may
include,
but
are
not
limited
to:
Categories
NAICS
Codes
Examples
of
potentially
affected
entities
Industry
111
Crop
production
112
Animal
production
311
Food
manufacturing
32532
Pesticide
manufacturing
This
listing
is
not
intended
to
be
exhaustive,
but
rather
provides
a
guide
for
readers
regarding
entities
likely
to
be
affected
by
this
action.
Other
types
of
entities
not
listed
in
the
table
could
also
be
affected.
The
North
American
Industrial
Classification
System
(
NAICS)
codes
have
been
provided
to
VerDate
Sep<
04>
2002
21:
00
Sep
17,
2002
Jkt
197001
PO
00000
Frm
00046
Fmt
4703
Sfmt
4703
E:\
FR\
FM\
18SEN1.
SGM
18SEN1
| epa | 2024-06-07T20:31:42.998821 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0192-0001/content.txt"
} |
EPA-HQ-OPP-2002-0194-0001 | Notice | "2002-08-30T04:00:00" | EPA Pesticide Program Dialogue Committee; Notice of Public Meeting. | <
PRE>
[
Federal
Register:
August
30,
2002
(
Volume
67,
Number
169)]
[
Notices]
[
Page
55839
55840]
From
the
Federal
Register
Online
via
GPO
Access
[
wais.
access.
gpo.
gov]
[
DOCID:
fr30au02
100]
ENVIRONMENTAL
PROTECTION
AGENCY
[
OPP
2002
0194;
FRL
7197
6]
EPA
Pesticide
Program
Dialogue
Committee;
Notice
of
Public
Meeting
AGENCY:
Environmental
Protection
Agency
(
EPA).
ACTION:
Notice.
SUMMARY:
EPA's
Office
of
Pesticide
Programs
will
hold
a
public
meeting
of
the
Pesticide
Program
Dialogue
Committee
(
PPDC)
on
September
17
and
18,
2002.
An
agenda
will
be
available
by
September
13,
2002,
and
posted
on
EPA's
Web
site
at
<
A
HREF="
http://
frwebgate.
access.
gpo.
gov/
cgi
bin/
leaving.
cg
i?
from=
leavingFR.
html&
log=
linklog&
to=
http://
www.
epa.
gov/
pesticides/
ppdc/">
www.
ep
a.
gov/
pesticides/
ppdc/</
A>.
An
agenda
is
being
developed
and
will
include
the
following
topics:
Alternative,
i.
e.,
non
animal
or
reduced
animal
testing
(
with
special
focus
on
acute
toxicity
testing),
pesticide
program
resource
allocations
and
expenditures,
follow
up
reports
from
the
May
2002,
PPDC
meeting,
and
other
topics.
DATES:
The
meeting
will
be
held
on
Tuesday,
September
17,
2002,
from
9
a.
m.
to
5
p.
m.,
and
on
Wednesday,
September
18,
2002,
from
9
a.
m.
to
3
p.
m.
ADDRESSES:
The
meeting
will
be
held
at
the
Old
Town
Holiday
Inn
Select,
480
King
Street,
Carlyle
Conference
Room
fifth
floor,
Alexandria,
VA.
Telephone:
(
703)
549
6080.
FOR
FURTHER
INFORMATION
CONTACT:
Margie
Fehrenbach,
Office
of
Pesticide
Programs
(
7501C),
Environmental
Protection
Agency,
1200
Pennsylvania
Avenue,
NW.,
Washington,
DC
20460;
telephone
number:
(
703)
308
4775;
fax
[[
Page
55840]]
number:
(
703)
308
4776;
e
mail
address:
<
A
HREF="
mailto:
fehrenbach.
margie@
epa.
go
v">
fehrenbach.
margie@
epa.
gov</
A>.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
This
action
is
directed
to
the
public
in
general.
This
action
may,
however
be
of
interest
to
persons
who
are
concerned
about
implementation
of
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(
FIFRA);
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA);
and
the
amendments
to
both
of
these
major
pesticide
laws
by
the
Food
Quality
Protection
Act
(
FQPA)
(
Public
Law
104
170)
of
1996.
Since
other
entities
may
also
be
interested,
the
Agency
has
not
attempted
to
describe
all
the
specific
entities
that
may
be
affected
by
this
action.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
this
Document
and
Other
Related
Documents?
1.
Electronically.
You
may
obtain
electronic
copies
of
this
document,
and
certain
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
at
<
A
HREF="
http://
frwebgate.
acc
ess.
gpo.
gov/
cgi
bin/
leaving.
cgi?
from=
leavingFR.
html&
log=
linklog&
to=
http://
www.
ep
a.
gov/">
http://
www.
epa.
gov/</
A>.
To
access
this
document,
on
the
Home
Page
select
``
Laws
and
Regulations,''
``
Regulations
and
Proposed
Rules,''
and
then
look
up
the
entry
for
this
document
under
the
``
Federal
Register
Environmental
Documents.''
You
can
also
go
directly
to
the
Federal
Register
listings
at
<
A
HREF="
http://
frwebgate.
access.
gpo.
gov/
cgi
bin/
leaving.
cgi?
from=
leavingFR.
h
tml&
log=
linklog&
to=
http://
www.
epa.
gov/
fedrgstr/">
http://
www.
epa.
gov/
fedrgstr/</
A
>.
To
access
information
about
PPDC,
go
directly
to
the
Home
Page
for
EPA's
Office
of
Pesticide
Programs
at
<
A
HREF="
http://
frwebgate.
access.
gpo.
gov/
cgi
bin/
leaving.
cgi?
from=
leavingFR.
html
&
log=
linklog&
to=
http://
www.
epa.
gov/
pesticides/
ppdc/">
http://
www.
epa.
gov/
pesticid
es/
ppdc/</
A>.
2.
In
person.
The
Agency
has
established
an
official
record
for
this
action
under
docket
ID
number
OPP
2002
0194.
The
official
record
consists
of
the
documents
specifically
referenced
in
this
action,
any
public
comments
received
during
an
applicable
comment
period,
and
other
information
related
to
this
action,
including
any
information
claimed
as
Confidential
Business
Information
(
CBI).
This
official
record
includes
the
documents
that
are
physically
located
in
the
docket,
as
well
as
the
documents
that
are
referenced
in
those
documents.
The
public
version
of
the
official
record,
which
includes
printed,
paper
versions
of
any
electronic
comments
submitted
during
an
applicable
comment
period,
is
available
for
inspection
in
the
Public
Information
and
Records
Integrity
Branch
(
PIRIB),
Rm.
119,
Crystal
Mall
<
greek
i>
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(
703)
305
5805.
II.
Background
The
PPDC
is
composed
of
42
members
appointed
by
EPA's
Deputy
Administrator.
Committee
members
were
selected
from
a
balanced
group
of
participants
from
the
following
sectors:
1.
Pesticide
user,
grower,
and
commodity
groups.
2.
Industry
and
trade
associations.
3.
Environmental/
public
interest
and
farmworker
groups.
4.
Federal,
State
and
tribal
governments.
5.
Public
health
organizations.
5.
Animal
welfare
and
academia.
PPDC
was
established
to
provide
a
public
forum
to
discuss
a
wide
variety
of
pesticide
regulatory
development
and
reform
initiatives,
evolving
public
policy,
program
implementation
issues,
science
policy
issues
associated
with
evaluating,
and
reducing
risks
from
use
of
pesticides.
III.
How
Can
I
Participate
in
this
Meeting?
The
PPDC
meetings
and
workshops
are
open
to
the
public
under
section
10(
a)(
2)
of
the
Federal
Advisory
Committee
Act
(
FACA),
Public
Law
92
463.
Outside
statements
by
observers
are
welcome.
Oral
statements
will
be
limited
to
3
to
5
minutes,
and
it
is
preferred
that
only
one
person
per
organization
present
the
statement.
Any
person
who
wishes
to
file
a
written
statement
may
do
so
before
or
after
the
meeting.
These
statements
will
become
part
of
the
permanent
record
and
will
be
available
for
public
inspection
at
the
address
in
Unit
I.
B.
2.
List
of
Subjects
Environmental
protection,
Pesticides
and
pests.
Dated:
August
26,
2002.
Marcia
E.
Mulkey,
Director,
Office
of
Pesticide
Programs.
[
FR
Doc.
<
strong>
02</
strong><
strong>
22219</
strong>
<
strong>
Filed</
strong>
8
27
<
strong>
02</
strong>;
4:
06
pm]
BILLING
CODE
6560
50
S
</
PRE>
| epa | 2024-06-07T20:31:43.004161 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0194-0001/content.txt"
} |
EPA-HQ-OPP-2002-0196-0001 | Notice | "2002-09-11T04:00:00" | Diazinon; Receipt of Request for Amendments and Cancellations. | 57589
Federal
Register
/
Vol.
67,
No.
176
/
Wednesday,
September
11,
2002
/
Notices
those
documents.
The
public
version
of
the
official
record
does
not
include
any
information
claimed
as
CBI.
The
public
version
of
the
official
record,
which
includes
printed,
paper
versions
of
any
electronic
comments
submitted
during
an
applicable
comment
period,
is
available
for
inspection
in
the
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Rm.
119,
Crystal
Mall
#2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(703)
305–
5805.
C.
How
and
To
Whom
Do
I
Submit
Comments?
You
may
submit
comments
through
the
mail,
in
person,
or
electronically.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP–
2002–
0197
in
the
subject
line
on
the
first
page
of
your
response.
1.
By
mail.
Submit
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Information
Resources
and
Services
Division
(7502C),
Office
of
Pesticide
Programs
(OPP),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460.
2.
In
person
or
by
courier.
Deliver
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Information
Resources
and
Services
Division
(7502C),
OPP,
Environmental
Protection
Agency,
Rm.
119,
Crystal
Mall
#2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA.
The
PIRIB
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(703)
305–
5805.
3.
Electronically.
You
may
submit
your
comments
electronically
by
e
mail
to:
opp
docket@
epa.
gov,
or
you
can
submit
a
computer
disk
as
described
above.
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
Avoid
the
use
of
special
characters
and
any
form
of
encryption.
Electronic
submissions
will
be
accepted
in
WordPerfect
6.1/
8.0
or
ASCII
file
format.
All
comments
in
electronic
form
must
be
identified
by
docket
ID
number
OPP–
2002–
0197.
Electronic
comments
may
also
be
filed
online
at
many
Federal
Depository
Libraries.
D.
How
Should
I
Handle
CBI
That
I
Want
To
Submit
to
the
Agency?
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
You
may
claim
information
that
you
submit
to
EPA
in
response
to
this
document
as
CBI
by
marking
any
part
or
all
of
that
information
as
CBI.
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
as
CBI
must
be
submitted
for
inclusion
in
the
public
version
of
the
official
record.
Information
not
marked
confidential
will
be
included
in
the
public
version
of
the
official
record
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
CBI,
please
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?
You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
1.
Explain
your
views
as
clearly
as
possible.
2.
Describe
any
assumptions
that
you
used.
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
your
views.
4.
If
you
estimate
potential
burden
or
costs,
explain
how
you
arrived
at
the
estimate
that
you
provide.
5.
Provide
specific
examples
to
illustrate
your
concerns.
6.
Offer
alternative
ways
to
improve
the
registration
activity.
7.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
notice.
8.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
ID
number
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
may
also
provide
the
name,
date,
and
Federal
Register
citation.
II.
Registration
Applications
EPA
received
applications
as
follows
to
register
pesticide
products
containing
new
active
ingredients
not
included
in
any
previously
registered
products
pursuant
to
the
provision
of
section
3(
c)(
4)
of
FIFRA.
Notice
of
receipt
of
these
applications
does
not
imply
a
decision
by
the
Agency
on
the
applications.
Products
Containing
Active
Ingredients
Not
Included
in
Any
Previously
Registered
Products
1.
File
Symbol:
3125–
LUR.
Applicant:
Bayer
Corporation,
8400
Hawthorn
Road,
Kansas
City
MO,
64120–
0013.Product
name:
Olympus
70%
Water
Dispersible
Granular
Herbicide.
Product
type:
Herbicide.
Active
ingredient:
Propoxycarbazone
sodium
(methyl
2[[[(
4,5
dihydro
4
methyl
5
oxo
3
propoxy
1H
1,2,4
triazol
1
yl)
carbonyl]
amino]
sulfonyl]
benzoate,
sodium
salt)
at
70%.
Proposed
classification/
Use:
None.
For
use
on
wheat
to
control
certain
grasses
and
broadleaf
weeds.
2.
File
Symbol:
3125–
LUE.
Applicant:
Bayer
Corp.
Product
name:
Olympus
70%
Water
Dispersible
Granular
Herbicide
in
Water
Soluble
Packets.
Product
type:
Herbicide.
Active
ingredient:
Propoxycarbazone
sodium
at
70%.
Proposed
classification/
Use:
None.
For
use
on
wheat
to
control
certain
grasses
and
broadleaf
weeds.
3.File
Symbol:
3125–
LUG.
Applicant:
Bayer
Corp.
Product
name:
Olympus
Technical
Herbicide.
Product
type:
Herbicide.
Active
ingredient:
Propoxycarbazone
sodium
at
95.3%.
Proposed
classification/
Use:
None.
For
manufacturing
use
of
end
use
products
to
be
used
to
control
certain
grasses
and
broadleaf
weeds
on
wheat.
List
of
Subjects
Environmental
protection,
Pesticides
and
pest.
Dated:
August
27,
2002.
Debra
Edwards,
Acting
Director,
Registration
Division,
Office
of
Pesticide
Programs.
[FR
Doc.
02–
22612
Filed
9–
10–
02;
8:
45
am]
BILLING
CODE
6560–
50–
S
ENVIRONMENTAL
PROTECTION
AGENCY
[OPP–
2002–
0196;
FRL–
7197–
8]
Diazinon;
Receipt
of
Requests
for
Amendments,
and
Cancellations
AGENCY:
Environmental
Protection
Agency
(EPA).
ACTION:
Notice.
SUMMARY:
Several
companies
that
manufacture
diazinon
[O,
O
diethyl
O
2
isopropyl
6
methyl
4
pyrimidinyl)
phosphorothioate]
pesticide
products
have
asked
EPA
to
cancel
or
amend
the
registrations
for
their
end
use
products
containing
diazinon
to
delete
all
indoor
uses,
certain
agricultural
uses
and
certain
outdoor
non
agricultural
uses.
Pursuant
to
section
6(
f)(
1)
of
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(FIFRA),
EPA
is
announcing
the
Agency's
receipt
of
these
requests.
These
requests
for
voluntary
termination
of
the
above
mentioned
uses
through
registration
cancellations
or
amendments
were
submitted
to
EPA
in
December
2001,
and
January,
February,
March,
April,
May,
June,
and
July
2002.
EPA
intends
to
grant
these
requests
by
issuing
a
cancellation
order
at
the
close
of
the
comment
period
for
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11,
2002
/
Notices
this
announcement
unless
the
Agency
receives
substantive
comments
within
the
comment
period
that
would
merit
its
further
review
of
these
requests.
Upon
the
issuance
of
the
cancellation
order,
any
distribution,
sale,
or
use
of
diazinon
products
listed
in
this
notice
will
only
be
permitted
if
such
distribution,
sale,
or
use
is
consistent
with
the
terms
of
that
order.
DATES:
Comments
on
the
requested
amendments
to
delete
uses
and
the
requested
registration
cancellations
must
be
submitted
to
the
address
provided
below
and
identified
by
docket
ID
number
OPP–
2002–
0196.
Comments
must
be
received
on
or
before
October
11,
2002.
ADDRESSES:
Comments
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP–
2002–
0196
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
Laura
Parsons,
Special
Review
and
Reregistration
Division
(7508C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(703)
305–
5776;
fax
number:
(703)
308–
7042;
e
mail
address:
parsons.
laura@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
This
announcement
consists
of
three
parts.
The
first
part
contains
general
information.
The
second
part
addresses
the
registrants'
requests
for
registration
cancellations
and
amendments
to
delete
uses.
The
third
part
proposes
existing
stocks
provisions
that
will
be
set
forth
in
the
cancellation
order
that
the
Agency
intends
to
issue
at
the
close
of
the
comment
period
for
this
announcement.
I.
General
Information
A.
Does
This
Action
Apply
to
Me?
This
action
is
directed
to
the
public
in
general.
You
may
be
potentially
affected
by
this
action
if
you
manufacture,
sell,
distribute,
or
use
diazinon
products.
The
Congressional
Review
Act,
5
U.
S.
C.
801
et
seq.,
as
added
by
the
Small
Business
Regulatory
Enforcement
Fairness
Act
of
1996,
does
not
apply
because
this
action
is
not
a
rule,
for
purposes
of
5
U.
S.
C.
804(
3).
Since
other
entities
may
also
be
interested,
the
Agency
has
not
attempted
to
describe
all
the
specific
entities
that
may
be
affected
by
this
action.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
This
Document
and
Other
Related
Documents?
1.
Electronically.
You
may
obtain
electronic
copies
of
this
document,
and
certain
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
at
http://
www.
epa.
gov/.
To
access
this
document,
on
the
Home
Page
select
``
Laws
and
Regulations,
''
``
Regulations
and
Proposed
Rules,
''
and
then
look
up
the
entry
for
this
document
under
the
Federal
Register—
Environmental
Documents.
You
can
also
go
directly
to
the
Federal
Register
listings
at
http://
www.
epa.
gov/
fedrgstr/.
To
access
information
about
the
risk
assessment
for
diazinon,
go
to
the
Home
Page
for
the
Office
of
Pesticide
Programs
or
go
directly
to
http://
www.
epa.
gov/
pesticides/
op/
diazinon.
htm.
2.
In
person.
The
Agency
has
established
an
official
record
for
this
action
under
docket
ID
number
OPP–
2002–
0196.
The
official
record
consists
of
the
documents
specifically
referenced
in
this
action,
any
public
comments
received
during
an
applicable
comment
period,
and
other
information
related
to
this
action,
including
any
information
claimed
as
Confidential
Business
Information
(CBI).
This
official
record
includes
the
documents
that
are
physically
located
in
the
docket,
as
well
as
the
documents
that
are
referenced
in
those
documents.
The
public
version
of
the
official
record
does
not
include
any
information
claimed
as
CBI.
The
public
version
of
the
official
record,
which
includes
printed,
paper
versions
of
any
electronic
comments
submitted
during
an
applicable
comment
period,
is
available
for
inspection
in
the
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Rm.
119,
Crystal
Mall
#2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(703)
305–
5805.
C.
How
and
To
Whom
Do
I
Submit
Comments?
You
may
submit
comments
through
the
mail,
in
person,
or
electronically.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP–
2002–
0196
in
the
subject
line
on
the
first
page
of
your
response.
1.
By
mail.
Submit
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Information
Resources
and
Services
Division
(7502C),
Office
of
Pesticide
Programs
(OPP),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460.
2.
In
person
or
by
courier.
Deliver
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Information
Resources
and
Services
Division
(7502C),
Office
of
Pesticide
Programs
(OPP),
Environmental
Protection
Agency,
Rm.
119,
Crystal
Mall
#2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA.
The
PIRIB
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(703)
305–
5805.
3.
Electronically.
You
may
submit
your
comments
electronically
by
e
mail
to:
opp
docket@
epa.
gov,
or
you
can
submit
a
computer
disk
as
described
above.
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
Avoid
the
use
of
special
characters
and
any
form
of
encryption.
Electronic
submissions
will
be
accepted
in
WordPerfect
6.1/
8.0/
9.0
or
ASCII
file
format.
All
comments
in
electronic
form
must
be
identified
by
docket
ID
number
OPP–
2002–
0196.
Electronic
comments
may
also
be
filed
online
at
many
Federal
Depository
Libraries.
D.
How
Should
I
Handle
CBI
That
I
Want
To
Submit
to
the
Agency?
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
You
may
claim
information
that
you
submit
to
EPA
in
response
to
this
document
as
CBI
by
marking
any
part
or
all
of
that
information
as
CBI.
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
as
CBI
must
be
submitted
for
inclusion
in
the
public
version
of
the
official
record.
Information
not
marked
confidential
will
be
included
in
the
public
version
of
the
official
record
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
CBI,
please
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?
You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
1.
Explain
your
views
as
clearly
as
possible.
2.
Describe
any
assumptions
that
you
used.
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Notices
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
your
views.
4.
If
you
estimate
potential
burden
or
costs,
explain
how
you
arrived
at
the
estimate
that
you
provide.
5.
Provide
specific
examples
to
illustrate
your
concerns.
6.
Offer
alternative
ways
to
improve
the
notice
or
collection
activity.
7.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
notice.
8.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
ID
number
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
may
also
provide
the
name,
date,
and
Federal
Register
citation.
II.
Receipt
of
Requests
to
Cancel
and
Amend
Registrations
to
Delete
Uses
A.
Background
Certain
registrants
requested
in
letters
dated
June,
August,
and
September
2001,
that
their
diazinon
registrations
be
amended
to
delete
all
indoor
uses,
certain
agricultural
uses,
and
any
other
uses
that
the
registrants
do
not
wish
to
maintain.
The
requests
also
included
deletions
of
outdoor
non
agricultural
uses
from
the
labeling
of
certain
end
use
products
so
that
such
products
would
be
labeled
for
agricultural
uses
only.
Similarly,
other
diazinon
end
use
registrants
requested
voluntary
cancellation
of
their
diazinon
end
use
registrations
with
indoor
use
and/
or
certain
outdoor
non
agricultural
uses,
and
any
other
uses
that
the
registrants
do
not
wish
to
maintain.
Pursuant
to
section
6(
f)(
1)
of
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(FIFRA),
EPA
is
announcing
the
Agency's
receipt
of
these
requests.
These
requested
cancellations
and
amendments
are
consistent
with
the
requests
in
December
2000
by
the
manufacturers
of
diazinon
technical
products,
and
EPA's
approval
of
such
requests,
to
terminate
all
indoor
uses
and
certain
agricultural
uses
from
their
diazinon
product
registrations
because
of
EPA's
concern
with
the
potential
exposure
risk,
especially
to
children.
The
indoor
uses
and
agricultural
uses
subject
to
cancellation
are
identified
in
List
1
below:
List
1—
Uses
to
be
Canceled
1.
Indoor
uses:
Pet
collars,
or
inside
any
structure
or
vehicle,
vessel,
or
aircraft
or
any
enclosed
area,
and/
or
on
any
contents
therein
(except
mushroom
houses),
including
but
not
limited
to
food/
feed
handling
establishments,
greenhouses,
schools,
residences,
commercial
buildings,
museums,
sports
facilities,
stores,
warehouses
and
hospitals.
2.
Agricultural
uses:
Alfalfa,
bananas,
Bermuda
grass,
dried
beans,
dried
peas,
celery,
red
chicory
(radicchio),
citrus,
clover,
coffee,
cotton,
cowpeas,
cucumbers,
dandelions,
forestry,
(ground
squirrel/
rodent
burrow,
dust
stations
for
public
health
use),
kiwi,
lespedeza,
parsley,
parsnips,
pastures,
peppers,
potatoes
(Irish
and
sweet),
sheep,
sorghum,
squash
(winter
and
summer),
rangeland,
Swiss
chard,
tobacco,
and
turnips
(roots
and
tops).
As
mentioned
above,
the
requests
announced
in
this
Federal
Register
notice
also
include
registration
cancellations
and/
or
amendments
to
terminate
certain
uses
that
the
registrants
do
not
wish
to
maintain.
The
specific
requests
are
identified
in
Tables
1
and
2.
EPA
has
begun
the
process
of
reviewing
the
requested
amendments
which
cannot
be
finalized
until
the
end
of
the
public
comment
period
and
provided
that
no
substantial
comments
need
to
be
addressed.
EPA
also
intends
to
grant
the
requested
product
and
use
cancellations
by
issuing
a
cancellation
order
at
the
close
of
the
comment
period
for
this
announcement
unless
the
Agency
receives
substantive
comments
within
the
comment
period
that
would
merit
its
further
review
of
these
requests.
B.
Requests
for
Voluntary
Cancellation
of
End
Use
Products
The
registrants
and
end
use
product
registrations
containing
diazinon
for
which
cancellation
was
requested
are
identified
in
the
following
Table
1.
TABLE
1.—
END
USE
PRODUCT
REGISTRATION
CANCELLATION
REQUESTS
Company
Registration
No.
Product
Farnam
Companies,
Inc.
270–
282
Diazinon
2EC
Prentiss
Inc.
655–
457
Prentox
Diazinon
4E
Insecticide
655–
462
Prentox
Diazinon
4S
Insecticide
655–
519
Prentox
Liquid
Household
Spray
#1
Universal
Cooperatives,
Inc.
1386–
573
Diazinon
Emulsifiable
Lawn
and
Garden
Insecticide
1386–
651
Security
Brand
2%
Diazinon
Granules
Lawn
Insect
Control
Virbac
AH,
Inc.
2382–
168
Diazinon
Pyriproxyfen
Collar
for
Dogs
and
Puppies
#1
2382–
171
Diazinon
Pyriproxyfen
Collar
for
Dogs
and
Puppies
#3
2382–
172
Diazinon
Pyriproxyfen
Collar
for
Dogs
and
Puppies
#2
ABC
Compounding,
Inc.
3862–
71
Drop
Dead
Insect
Spray
Cerexagri,
Inc.
4581–
335
Knox
Out
2
FM
Amvac
Chemical
Corp.
5481–
224
Diazinon
4E
5481–
241
Alco
Housing
Authority
Roach
Concentrate
U.
S.
Marketing
Distributors
6409–
14
Professional
Do
it
Yourself
Exterminator's
Kit
Formula
400
Voluntary
Purchasing
Group
Inc.
7401–
67
Ferti
Lome
Rose
Spray
Containing
Diazinon
and
Daconil
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11,
2002
/
Notices
TABLE
1.—
END
USE
PRODUCT
REGISTRATION
CANCELLATION
REQUESTS—
Continued
Company
Registration
No.
Product
Earth
Care/
Division
of
United
Industries
Corp.
8660–
101
Vertagreen
5%
Diazinon
Insecticide
8660–
106
Vertagreen
Diazion
Pre
Weed
8660–
115
Vertagreen
Diazinon
Pre
Weed
Plus
The
Andersons
Lawn
Fertilizer
Division
9198–
189
Proturf
Insecticide
One
Waterbury
Companies,
Inc.
9444–
89
CB
Aqueous
Residual
Insecticide
Athea
Laboratories,
Inc.
10088–
71
Roach
and
Ant
Killer
Verpas
Products,
Inc.
13926–
6
Diaciclon
F–
5
Wagnol
Inc.
33912–
1
Wagnol
40
Pest
Control
Spray
Concentrate
Contains
Diazinon
T
Tex
Corp.
39039–
5
Dryzon
WP
Livestock
Premise
and
Sheep
Insecticide
Chem
Tech
Ltd.
47000–
63
Pressurized
Household
Insect
Spray
Concentrate
Contains
Diazinon
and
DDVP
Marman
USA,
Inc.
48273–
25
Marman
Diazinon
AG
60
EC
Control
Solutions
Inc
53883–
58
Martin's
Diazinon
4E
Indoor
Outdoor
Insecticide
Arkopharma,
Inc.
69607–
1
Double
Duty
Flea
and
Tick
Collar
for
Dogs
Under
section
6(
f)(
1)(
A)
of
FIFRA,
registrants
may
request,
at
any
time,
that
EPA
cancel
any
of
their
pesticide
registrations.
Section
6(
f)(
1)(
B)
of
FIFRA
requires
that
EPA
provide
a
30–
day
period
in
which
the
public
may
comment
before
the
Agency
may
act
on
the
request
for
voluntary
cancellation.
In
addition,
section
6(
f)(
1)(
C)
of
FIFRA
requires
that
EPA
provide
a
180–
day
comment
period
on
a
request
for
voluntary
termination
of
any
minor
agricultural
use
before
granting
the
request,
unless:
1.
The
registrants
request
a
waiver
of
the
comment
period.
2.
The
Administrator
determines
that
continued
use
of
the
pesticide
would
pose
an
unreasonable
adverse
effect
on
the
environment.
In
this
case,
all
of
the
registrants
have
requested
that
EPA
waive
the
180–
day
comment
period.
In
light
of
this
request,
EPA
is
granting
the
request
to
waive
the
180–
day
comment
period
and
is
providing
a
30–
day
public
comment
period
before
taking
action
on
the
requested
cancellations.
Because
of
risk
concerns
posed
by
certain
uses
of
diazinon,
EPA
intends
to
grant
the
requested
cancellations
at
the
close
of
the
comment
period
for
this
announcement
unless
the
Agency
receives
any
substantive
comment
within
the
comment
period
that
would
merit
its
further
review
of
these
requests.
C.
Requests
for
Voluntary
Amendments
To
Delete
Uses
From
the
Registrations
of
End
Use
Products
Pursuant
to
section
6(
f)(
1)(
A)
of
FIFRA,
the
following
companies
have
submitted
a
request
to
amend
the
registrations
of
their
pesticide
end
use
products
containing
diazinon
to
delete
certain
uses
from
certain
products.
The
following
Table
2
identifies
the
registrants,
the
product
registrations
that
they
wish
to
amend,
and
the
uses
that
they
wish
to
delete
through
registration
amendments.
TABLE
2.—
END
USE
PRODUCT
REGISTRATION
AMENDMENT
REQUESTS
Company
Registration
No.
Product
Name:
Use
Deletions
Dragon
Chemical
Corp.
16–
119
Dragon
5%
Diazinon
Granules:
Celery
16–
157
Diazinon
25%
Diazinon
Spray:
Almonds
16–
166
Dragon
Diazinon
Water
Based
Concentrate:
Almonds
Southern
Agricultural
Insecticides,
Inc.
829–
264
SA–
50
Brand
5%
Diazinon
Granules:
Celery
Universal
Cooperative,
Inc.
1386–
599
Diazinon
4
EC
(AG):
Beans,
cucumbers,
parsley,
parsnips,
peas,
peppers,
potatoes
(Irish),
squash
(summer
and
winter),
sweet
potatoes
Swiss
chard,
turnips,
lawn
pest
control,
nuisance
pests
in
outside
areas,
grassland
insects,
and
indoor
ornamentals
1386–
648
5%
Diazinon
Insect
Killer
Granules:
Celery
Knox
Fertilizer
Co.
Inc.
8378–
32
Shaw's
5%
Diazinon
Insect
Granules:
Celery
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Register
/
Vol.
67,
No.
176
/
Wednesday,
September
11,
2002
/
Notices
Under
section
6(
f)(
1)(
A)
of
FIFRA,
registrants
may
request,
at
any
time,
that
their
pesticide
registrations
be
amended
to
delete
one
or
more
pesticide
uses.
The
afore
mentioned
companies
have
requested
to
amend
their
registrations
and
have
requested
that
EPA
waive
the
180–
day
comment
period.
In
light
of
this
request,
EPA
is
granting
the
request
to
waive
the
180–
day
comment
period
and
is
providing
a
30–
day
public
comment
period
before
taking
action
on
the
requested
amendments
to
delete
uses.
Because
of
risk
concerns
posed
by
certain
uses
of
diazinon,
EPA
intends
to
grant
the
requested
amendments
to
delete
uses
at
the
close
of
the
comment
period
for
this
announcement,
unless
the
Agency
receives
any
substantive
comment
within
the
comment
period
that
would
merit
its
further
review
of
these
requests.
III.
Proposed
Existing
Stocks
Provisions
EPA
received
requests
for
voluntary
cancellation
of
the
diazinon
registrations
identified
in
Table
1
and
requests
for
amendments
to
terminate
certain
uses
of
the
diazinon
registrations
identified
in
Table
2.
Pursuant
to
section
6(
f)
of
FIFRA,
EPA
intends
to
grant
these
requests
by
issuing
a
cancellation
order
at
the
end
of
the
30–
day
comment
period
unless
the
Agency
receives
any
substantive
comment
within
the
comment
period
that
would
merit
its
further
review
of
these
requests.
In
the
event
that
EPA
issues
a
cancellation
order,
EPA
intends
to
include
in
that
order
the
existing
stocks
provisions
set
forth
in
this
section.
For
purposes
of
that
cancellation
order,
the
term
``
existing
stocks''
will
be
defined,
pursuant
to
EPA's
existing
stocks
policy
at
56
FR
29362,
of
June
26,
1991,
as
those
stocks
of
a
registered
pesticide
product
which
are
currently
in
the
United
States
and
which
have
been
packaged,
labeled,
and
released
for
shipment
prior
to
the
effective
date
of
the
cancellation
or
amendment.
Any
distribution,
sale,
or
use
of
existing
stocks
after
the
effective
date
of
the
cancellation
order
that
the
Agency
intends
to
issue
that
is
not
consistent
with
the
terms
of
that
order
will
be
considered
a
violation
of
section
12(
a)(
2)(
K)
and/
or
12(
a)(
1)(
A)
of
FIFRA.
EPA
intends
that
the
cancellation
order
includes
the
following
existing
stocks
provisions:
1.
Distribution
or
sale
of
products
bearing
instructions
for
use
on
agricultural
crops.
The
distribution
or
sale
of
existing
stocks
by
the
registrant
of
any
product
listed
in
Table
1
or
2
that
bears
instructions
for
use
on
the
agricultural
crops
identified
in
List
1
will
not
be
lawful
under
FIFRA
1–
year
after
the
effective
date
of
the
cancellation
order.
Persons
other
than
the
registrant
may
continue
to
sell
or
distribute
the
existing
stocks
of
any
product
listed
in
Table
1
or
2
that
bears
instructions
for
any
of
the
agricultural
uses
identified
in
List
1
after
the
effective
date
of
the
cancellation
order.
However,
it
is
lawful
to
ship
such
stocks
for
export
consistent
with
the
requirements
of
section
17
of
FIFRA,
or
to
properly
dispose
of
the
existing
stocks
in
accordance
with
all
applicable
law.
2.
Distribution
or
sale
of
products
bearing
instructions
for
use
on
outdoor
non
agricultural
sites.
The
distribution
or
sale
of
existing
stocks
by
the
registrant
of
any
product
listed
in
Table
1
or
2
that
bears
instructions
for
use
on
outdoor
non
agricultural
sites
will
not
be
lawful
under
FIFRA
1–
year
after
the
effective
date
of
the
cancellation
order.
Persons
other
than
the
registrant
may
continue
to
sell
or
distribute
the
existing
stocks
of
any
product
listed
in
Table
1
or
2
that
bears
instructions
for
use
on
outdoor
non
agricultural
sites
after
the
effective
date
of
the
cancellation
order.
However,
it
is
lawful
to
ship
such
stocks
for
export
consistent
with
the
requirements
of
section
17
of
FIFRA,
or
to
properly
dispose
of
the
existing
stocks
in
accordance
with
all
applicable
law.
3.
Distribution
or
sale
of
products
bearing
instructions
for
use
on
indoor
sites.
The
distribution
or
sale
of
existing
stocks
by
the
registrant
of
any
product
listed
in
Table
1
or
2
that
bears
instructions
for
use
at
or
on
any
indoor
sites
(except
mushroom
houses),
shall
not
be
lawful
under
FIFRA
as
of
the
effective
date
of
the
cancellation
order,
except
for
shipping
stocks
for
export
consistent
with
the
requirements
of
section
17
of
FIFRA,
or
properly
disposing
of
the
existing
stocks
in
accordance
with
all
applicable
law.
4.
Retail
and
other
distribution
or
sale
of
existing
stock
of
products
for
indoor
use.
The
distribution
or
sale
of
existing
stocks
by
any
person
other
than
the
registrants
of
products
listed
in
Table
1
or
2
bearing
instructions
for
any
indoor
uses
except
mushroom
houses
will
not
be
lawful
under
FIFRA
after
December
31,
2002,
except
for
shipping
stocks
for
export
consistent
with
the
requirements
of
section
17
of
FIFRA,
or
properly
disposing
of
the
existing
stocks
in
accordance
with
all
applicable
law.
5.
Use
of
existing
stocks.
EPA
intends
to
permit
the
use
of
existing
stocks
of
products
listed
in
Table
1
or
2
until
such
stocks
are
exhausted,
provided
such
use
is
in
accordance
with
the
existing
labeling
of
that
product.
List
of
Subjects
Environmental
protection,
Pesticides
and
pests.
Dated:
August
29,
2002.
Susan
Lewis,
Acting
Director,
Special
Review
and
Reregistration
Division,
Office
of
Pesticide
Programs.
[FR
Doc.
02–
22989
Filed
9–
10–
02;
8:
45
am]
BILLING
CODE
6560–
50–
S
ENVIRONMENTAL
PROTECTION
AGENCY
[OPP–
2002–
0236;
FRL–
7198–
1]
Notice
of
Filing
a
Pesticide
Petition
To
Establish
a
Tolerance
for
a
Certain
Pesticide
Chemical
in
or
on
Food
AGENCY:
Environmental
Protection
Agency
(EPA).
ACTION:
Notice.
SUMMARY:
This
notice
announces
the
initial
filing
of
a
pesticide
petition
proposing
the
establishment
of
regulations
for
residues
of
a
certain
pesticide
chemical
in
or
on
various
food
commodities.
DATES:
Comments,
identified
by
docket
ID
number
OPP–
2002–
0236
must
be
received
on
or
before
October
11,
2002.
ADDRESSES:
Comments
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
Unit
I.
C.
of
the
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP–
2002–
0236
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
By
mail:
Jim
Tompkins,
Registration
Division
(7505C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(703)
305–
5704;
and
e
mail
address:
tompkins.
jim@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
This
Action
Apply
to
Me?
You
may
be
affected
by
this
action
if
you
are
an
agricultural
producer,
food
manufacturer
or
pesticide
manufacturer.
Potentially
affected
categories
and
entities
may
include,
but
are
not
limited
to:
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| epa | 2024-06-07T20:31:43.008485 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0196-0001/content.txt"
} |
EPA-HQ-OPP-2002-0202-0001 | Notice | "2002-09-23T04:00:00" | Lindane Reregistration Eligibility Decision (RED) Notice of Availability for Comment | 59500
Federal
Register
/
Vol.
67,
No.
184
/
Monday,
September
23,
2002
/
Notices
establish
a
Spinning
Reserve
market
for
PJM
and
PJM
West
and
new
compensation
rules.
PJM
amended
its
August
29,
2002
filing
to
include
conforming
amendments
to
both
the
PJM
Tariff
and
Operating
Agreement
consistent
with
the
proposed
Spinning
Reserve
market
and
new
compensation
rules.
PJM
requests
an
effective
date
of
December
1,
2002
for
the
amendments
filed
on
August
29,
2002
and
September
11,
2002.
Copies
of
this
filing
were
served
upon
all
parties
listed
on
the
official
service
list
in
Docket
No.
ER02–
2519–
000,
all
PJM
members,
and
each
state
electric
utility
regulatory
commission
in
the
PJM
control
area
and
PJM
West
region.
Comment
Date:
October
2,
2002.
7.
PJM
Interconnection,
L.
L.
C.
[Docket
No.
ER02–
2547–
000]
Take
notice
that
on
September
10,
2002
PJM
Interconnection,
L.
L.
C.
(PJM),
submitted
for
filing
an
executed
interim
interconnection
service
agreement
between
PJM
and
Dominion
Equipment,
Inc.
and
an
executed
interconnection
service
agreement
between
PJM
and
Fairless
Energy,
LLC.
PJM
requests
a
waiver
of
the
Commission's
60
day
notice
requirement
to
permit
the
effective
dates
agreed
to
by
the
parties.
Copies
of
this
filing
were
served
upon
each
of
the
parties
to
the
agreements
and
the
state
regulatory
commissions
within
the
PJM
region.
Comment
Date:
October
1,
2002.
8.
New
York
Independent
System
Operator,
Inc.
[Docket
No.
ER02–
2548–
000]
Take
notice
that
on
September
11,
2002,
the
New
York
Independent
System
Operator,
Inc.
(NYISO)
filed
revisions
to
its
Market
Administration
and
Control
Area
Services
Tariff
(Services
Tariff)
to
provide
further
clarity
and
improve
the
administration
of
the
Installed
Capacity
market
in
the
New
York
Control
Area.
The
NYISO
has
served
a
copy
of
this
filing
to
all
parties
that
have
executed
Service
Agreements
under
the
NYISO's
Open
Access
Transmission
Tariff
or
Services
Tariff,
the
New
York
State
Public
Service
Commission
and
to
the
electric
utility
regulatory
agencies
in
New
Jersey
and
Pennsylvania.
Comment
Date:
October
2,
2002.
9.
Occidental
Power
Services,
Inc.
[Docket
No.
ER02–
2549–
000]
Take
notice
that
on
September
12,
2002,
Occidental
Power
Services,
Inc.
(OPSI)
tendered
for
filing
a
proposed
amendment
to
the
Western
Systems
Power
Pool
(WSPP).
The
proposed
amendment
reflects
the
admission
of
OPSI
to
membership
in
the
WSPP.
OPSI
requests
that
the
Commission
authorize
the
proposed
amendment
to
become
effective
on
September
12,
2002.
Comment
Date:
October
3,
2002.
10.
Tenaska
Oxy
Power
Services,
L.
P.
[Docket
No.
ER02–
2550–
000]
Take
notice
that
on
September
12,
2002,
Tenaska
Oxy
Power
Services,
L.
P.,
1701
E.
Lamar
Boulevard,
Suite
100,
Arlington,
TX
76006
(TOPS)
submitted
for
filing
with
the
Federal
Energy
Regulatory
Commission
an
application
for
blanket
authorization
and
certain
waivers
under
regulations
of
the
Commission,
and
for
an
order
accepting
its
Rate
Schedule
FERC
No.
1
to
be
effective
the
earlier
of
November
11,
2002,
or
the
date
of
a
Commission
order
granting
approval
of
its
Rate
Schedule.
TOPS
intends
to
engage
in
electric
power
and
energy
transactions
as
a
marketer
and
a
broker.
In
transactions
where
TOPS
purchases
power,
including
capacity
and
related
services
from
electric
utilities,
qualifying
facilities,
and
independent
power
producers,
and
resells
such
power
to
other
purchasers,
TOPS
will
be
functioning
as
a
marketer.
In
TOPS'
marketing
transactions,
TOPS
proposes
to
charge
rates
mutually
agreed
upon
by
the
parties.
In
transactions
where
TOPS
does
not
take
title
to
electric
power
and/
or
energy,
TOPS
will
be
limited
to
the
role
of
a
broker
and
will
charge
a
fee
for
its
services.
TOPS
is
not
in
the
business
of
producing
electric
power
nor
does
it
contemplate
acquiring
title
to
any
electric
power
transmission
facilities.
Comment
Date:
October
3,
2002.
Standard
Paragraph
E.
Any
person
desiring
to
intervene
or
to
protest
this
filing
should
file
with
the
Federal
Energy
Regulatory
Commission,
888
First
Street,
NE.,
Washington,
DC
20426,
in
accordance
with
Rules
211
and
214
of
the
Commission's
rules
of
practice
and
procedure
(18
CFR
385.211
and
385.214).
Protests
will
be
considered
by
the
Commission
in
determining
the
appropriate
action
to
be
taken,
but
will
not
serve
to
make
protestants
parties
to
the
proceeding.
Any
person
wishing
to
become
a
party
must
file
a
motion
to
intervene.
All
such
motions
or
protests
should
be
filed
on
or
before
the
comment
date,
and,
to
the
extent
applicable,
must
be
served
on
the
applicant
and
on
any
other
person
designated
on
the
official
service
list.
This
filing
is
available
for
review
at
the
Commission
or
may
be
viewed
on
the
Commission's
web
site
at
http://
www.
ferc.
gov
using
the
``
RIMS''
link,
select
``
Docket
#''
and
follow
the
instructions
(call
202–
208–
2222
for
assistance).
Protests
and
interventions
may
be
filed
electronically
via
the
Internet
in
lieu
of
paper;
See
18
CFR
385.2001(
a)(
1)(
iii)
and
the
instructions
on
the
Commission's
web
site
under
the
``
e
Filing''
link.
Magalie
R.
Salas,
Secretary.
[FR
Doc.
02–
24040
Filed
9–
20–
02;
8:
45
am]
BILLING
CODE
6717–
01–
P
ENVIRONMENTAL
PROTECTION
AGENCY
[OPP–
2002–
0202;
FRL–
7273–
8]
Lindane
Reregistration
Eligibility
Decision
(RED);
Notice
of
Availability
for
Comment
AGENCY:
Environmental
Protection
Agency
(EPA)
ACTION:
Notices.
SUMMARY:
This
notice
announces
the
availability
of
the
Reregistration
Eligibility
Decision
(RED)
document
and
technical
support
documents
for
the
pesticide
active
ingredient,
lindane.
These
documents
have
been
developed
using
a
public
participation
process
designed
by
the
EPA
and
the
U.
S.
Department
of
Agriculture
(USDA)
to
involve
the
public
in
the
reassessment
of
pesticide
tolerances
under
the
Food
Quality
Protection
Act
(FQPA)
and
the
reregistration
of
individual
pesticides
under
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(FIFRA).
This
notice
starts
a
60–
day
public
comment
period
for
lindane,
during
which
the
public
is
invited
to
submit
comments
on
the
Agency's
risk
management
decision.
DATES:
Comments,
identified
by
docket
ID
number
OPP–
2002–
0202,
must
be
received
on
or
before
November
22,
2002
ADDRESSES:
Comments
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP–
2002–
0202
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
Mark
Howard,
Special
Review
and
Reregistration
Division
(7508C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(703)
308–
8172;
fax
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/
Vol.
67,
No.
184
/
Monday,
September
23,
2002
/
Notices
number:
(703)
308–
8005;
e
mail
address:
howard.
markt@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
This
action
is
directed
to
the
public
in
general,
nevertheless,
a
wide
range
of
stakeholders
will
be
interested
in
obtaining
the
revised
risk
assessments
and
submitting
risk
management
comments
on
lindane
including
environmental,
human
health,
and
agricultural
advocates;
the
chemical
industry;
pesticide
users;
and
members
of
the
public
interested
in
the
use
of
pesticides
on
food.
As
such,
the
Agency
has
not
attempted
to
specifically
describe
all
the
entities
potentially
affected
by
this
action.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
this
Document
and
Other
Related
Documents?
1.
Electronically.
You
may
obtain
electronic
copies
of
this
document,
and
most
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
at
http://
www.
epa.
gov/.
To
access
this
document,
on
the
Home
Page
select
``
Laws
and
Regulations,
''
``
Regulations
and
Proposed
Rules,
''
and
then
look
up
the
entry
for
this
document
under
the
``
Federal
Register
—Environmental
Documents.
''
You
can
also
go
directly
to
the
FEDERAL
REGISTER
listings
at
http://
www.
epa.
gov/
fedrgstr/.
You
can
obtain
copies
of
the
RED
and
related
documents
discussed
in
this
notice
from
EPA's
Office
of
Pesticide
Programs'
Home
Page,
http://
www.
epa.
gov/
pesticides/
using
the
following
links:
``
Reregistration
Eligibility
(REDs)
''
under
the
heading
``
Reregistration
and
Special
Review''
and
then
``
Lindane.
''
You
can
also
go
directly
to
the
``
Lindane
RED''
at
http:/
/www.
epa.
gov/
pesticides/
reregistration/
status.
htm.
Available
documents
include
the
RED,
supporting
technical
documents,
and
FEDERAL
REGISTER
notices.
Information
on
pesticide
reregistration
and
tolerance
reassessment,
including
the
purpose
and
status
of
Agency
programs
to
complete
REDs,
Interim
REDs,
and
tolerance
reassessment
decisions
(TREDs),
is
available
at
http://
www.
epa.
gov/
pesticides/
tolerance.
General
information
is
available
on
the
Office
of
Pesticide
Programs'
Home
Page,
http://
www.
epa.
gov/
pesticides/.
2.
In
person.
The
Agency
has
established
an
official
record
for
this
action
under
docket
ID
number
OPP–
2002–
0202.
The
official
record
consists
of
the
documents
specifically
referenced
in
this
action,
and
other
information
related
to
this
action,
including
any
information
claimed
as
Confidential
Business
Information
(CBI).
This
official
record
includes
the
documents
that
are
physically
located
in
the
docket,
as
well
as
the
documents
that
are
referenced
in
those
documents.
The
public
version
of
the
official
record
does
not
include
any
information
claimed
as
CBI.
The
public
version
of
the
official
record,
which
includes
printed,
paper
versions
of
any
electronic
comments
submitted
during
an
applicable
comment
period,
is
available
for
inspection
in
the
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Rm.
119,
Crystal
Mall
#2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA,
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(703)
305–
5805.
C.
How
and
to
Whom
Do
I
Submit
Comments?
You
may
submit
comments
on
any
part
of
the
RED
through
the
mail,
in
person,
or
electronically.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP–
2002–
0202
in
the
subject
line
on
the
first
page
of
your
response.
1.
By
mail.
Submit
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Information
Resources
and
Services
Division
(7502C),
Office
of
Pesticide
Programs
(OPP),
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460.
2.
In
person
or
by
courier.
Deliver
your
comments
to:
Public
Information
and
Records
Integrity
Branch
(PIRIB),
Information
Resources
and
Services
Division
(7502C),
Office
of
Pesticide
Programs
(OPP),
Environmental
Protection
Agency,
Rm.
119,
Crystal
Mall
#2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA.
The
PIRIB
is
open
from
8:
30
a.
m.
to
4
p.
m.,
Monday
through
Friday,
excluding
legal
holidays.
The
PIRIB
telephone
number
is
(703)
305–
5805.
3.
Electronically.
You
may
submit
your
comments
electronically
by
e
mail
to:
opp
docket@
epa.
gov,
or
you
can
submit
a
computer
disk
as
described
above.
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
Avoid
the
use
of
special
characters
and
any
form
of
encryption.
Electronic
submissions
will
be
accepted
in
WordPerfect
6.1/
8.0/
9.0
or
ASCII
file
format.
All
comments
in
electronic
form
must
be
identified
by
docket
ID
number
OPP–
2002–
0202.
Electronic
comments
may
also
be
filed
online
at
many
Federal
Depository
Libraries.
D.
How
Should
I
Handle
CBI
that
I
Want
to
Submit
to
the
Agency?
Do
not
submit
any
information
electronically
that
you
consider
to
be
CBI.
You
may
claim
information
that
you
submit
to
EPA
in
response
to
this
document
as
CBI
by
marking
any
part
or
all
of
that
information
as
CBI.
Information
so
marked
will
not
be
disclosed
except
in
accordance
with
procedures
set
forth
in
40
CFR
part
2.
In
addition
to
one
complete
version
of
the
comment
that
includes
any
information
claimed
as
CBI,
a
copy
of
the
comment
that
does
not
contain
the
information
claimed
as
CBI
must
be
submitted
for
inclusion
in
the
public
version
of
the
official
record.
Information
not
marked
confidential
will
be
included
in
the
public
version
of
the
official
record
without
prior
notice.
If
you
have
any
questions
about
CBI
or
the
procedures
for
claiming
CBI,
please
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
E.
What
Should
I
Consider
as
I
Prepare
My
Comments
for
EPA?
You
may
find
the
following
suggestions
helpful
for
preparing
your
comments:
1.
Explain
your
views
as
clearly
as
possible.
2.
Describe
any
assumptions
that
you
used.
3.
Provide
copies
of
any
technical
information
and/
or
data
you
used
that
support
your
views.
4.
If
you
estimate
potential
burden
or
costs,
explain
how
you
arrived
at
the
estimate
that
you
provide.
5.
Provide
specific
examples
to
illustrate
your
concerns.
6.
Offer
alternative
ways
to
improve
the
notice
or
collection
activity.
7.
Make
sure
to
submit
your
comments
by
the
deadline
in
this
notice.
8.
To
ensure
proper
receipt
by
EPA,
be
sure
to
identify
the
docket
ID
number
assigned
to
this
action
in
the
subject
line
on
the
first
page
of
your
response.
You
may
also
provide
the
name,
date,
and
Federal
Register
citation.
II.
Background
A.
What
Action
is
the
Agency
Taking?
The
Agency
has
issued
a
RED
for
the
pesticide
active
ingredient
lindane.
Under
FIFRA,
as
amended
in
1988
and
1996,
EPA
is
conducting
an
accelerated
reregistration
program
to
re
evaluate
existing
pesticides
to
make
sure
they
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/
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No.
184
/
Monday,
September
23,
2002
/
Notices
meet
current
scientific
and
regulatory
standards.
The
data
base
to
support
the
reregistration
of
lindane
is
substantially
complete,
and
the
Agency
has
identified
risk
mitigation
measures
that,
if
adopted
by
the
registrant,
will
address
the
human
health
and
ecological
risks
associated
with
the
remaining
uses
of
lindane.
As
part
of
the
lindane
RED,
the
Agency
will
revoke
all
existing
lindane
tolerances
because
all
lindane
products
for
which
the
tolerances
were
originally
established
have
been
cancelled.
The
Agency
has
also
determined
that
the
currently
registered
lindane
seed
treatment
products
would
be
eligible
for
reregistration
if
the
registrants
make
the
changes
to
the
terms
and
conditions
specified
in
the
lindane
RED
and
provide
the
required
data,
and
if
EPA
is
able
to
establish
all
required
tolerances
for
residues
of
lindane
in
food.
The
RED
document
includes
guidance
and
time
frames
for
complying
with
any
label
changes
for
products
containing
lindane.
The
reregistration
program
is
being
conducted
under
Congressionally
mandated
time
frames,
and
EPA
recognizes
both
the
need
to
make
timely
reregistration
decisions
and
to
involve
the
public.
Therefore,
EPA
is
issuing
the
lindane
RED
as
a
final
document
with
a
60
day
public
comment
period.
Although
the
60
day
comment
period
does
not
affect
the
registrants's
response
due
date,
it
is
intended
to
provide
an
opportunity
for
public
input
and
a
mechanism
for
initiating
any
necessary
amendments
to
the
RED.
All
comments
will
be
carefully
considered
by
the
Agency.
If
any
comment
significantly
affects
the
lindane
RED,
EPA
will
amend
the
RED
by
publishing
the
amendment
in
the
Federal
Register.
B.
What
is
the
Agency's
Authority
for
Taking
this
Action?
The
legal
authority
for
these
RED
falls
under
FIFRA,
as
amended
in
1988
and
1996.
Section
4(
g)(
2)(
A)
of
FIFRA
directs
that,
after
submission
of
all
data
concerning
a
pesticide
active
ingredient,``
the
Administrator
shall
determine
whether
pesticides
containing
such
active
ingredient
are
eligible
for
reregistration.
''
List
of
Subjects
Environmental
protection,
Lindane,
Pesticides
and
pests.
Dated:
September
13,
2002.
Lois
Ann
Rossi,
Director,
Special
Review
and
Reregistration
Division,
Office
of
Pesticide
Programs.
[FR
Doc.
02–
24096
Filed
9–
20–
02;
8:
45
am]
BILLING
CODE
6560–
50–
S
ENVIRONMENTAL
PROTECTION
AGENCY
[OPP–
2002–
0252;
FRL–
7200–
9]
Thiabendazole
and
Salts;
Availability
of
Reregistration
Eligibility
Decision
Documents
for
Comment
AGENCY:
Environmental
Protection
Agency
(EPA).
ACTION:
Notice.
SUMMARY:
This
notice
announces
availability
and
starts
a
60–
day
public
comment
period
on
the
Reregistration
Eligibility
Decision
(RED)
documents
for
the
pesticide
active
ingredients
thiabendazole
and
salts.
The
RED
represents
EPA's
formal
regulatory
assessment
of
the
health
and
environmental
data
base
of
the
subject
chemical
and
presents
the
Agency's
determination
regarding
which
pesticidal
uses
are
eligible
for
reregistration.
DATES:
Comments,
identified
by
docket
ID
number
OPP–
2002–
0252,
must
be
received
on
or
before
November
22,
2002.
ADDRESSES:
Comments
may
be
submitted
by
mail,
electronically,
or
in
person.
Please
follow
the
detailed
instructions
for
each
method
as
provided
in
Unit
I.
of
the
SUPPLEMENTARY
INFORMATION.
To
ensure
proper
receipt
by
EPA,
it
is
imperative
that
you
identify
docket
ID
number
OPP–
2002–
0252
in
the
subject
line
on
the
first
page
of
your
response.
FOR
FURTHER
INFORMATION
CONTACT:
By
mail:
Lorilyn
Montford,
Special
Review
and
Reregistration
Division
(7508C),
Office
of
Pesticide
Programs,
Environmental
Protection
Agency,
1200
Pennsylvania
Ave.,
NW.,
Washington,
DC
20460;
telephone
number:
(703)
308–
8170;
e
mail
address:
montford.
lorilyn@
epa.
gov.
SUPPLEMENTARY
INFORMATION:
I.
General
Information
A.
Does
this
Action
Apply
to
Me?
This
action
is
directed
to
the
public
in
general.
This
action
may,
however,
be
of
interest
to
persons
who
are
or
may
be
required
to
conduct
testing
of
chemical
substances
under
the
Federal
Insecticide,
Fungicide,
and
Rodenticide
Act
(FIFRA)
or
the
Federal
Food,
Drug,
and
Cosmetic
Act
(FFDCA);
environmental,
human
health,
and
agricultural
advocates;
pesticides
users;
and
members
of
the
public
interested
in
the
use
of
pesticides.
Since
other
entities
may
also
be
interested,
the
Agency
has
not
attempted
to
describe
all
the
specific
entities
that
may
be
affected
by
this
action.
If
you
have
any
questions
regarding
the
applicability
of
this
action
to
a
particular
entity,
consult
the
person
listed
under
FOR
FURTHER
INFORMATION
CONTACT.
B.
How
Can
I
Get
Additional
Information,
Including
Copies
of
this
Document
and
Other
Related
Documents?
1.
Electronically.
You
may
obtain
electronic
copies
of
this
document,
and
certain
other
related
documents
that
might
be
available
electronically,
from
the
EPA
Internet
Home
Page
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VerDate
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} |
EPA-HQ-OPP-2002-0202-0002 | Supporting & Related Material | "2002-08-14T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
July
31,
2002
MEMORANDUM
SUBJECT:
Revised
HED
Risk
Assessment
for
Lindane.
DP
Barcode
D284581
Reregistration
Case
#
0315;
PC
code
009001
FROM:
Becky
Daiss,
Environmental
Health
Scientist
Reregistration
Branch
4
Health
Effects
Division
(7509C)
THRU:
Susan
V.
Hummel,
Branch
Senior
Scientist
Reregistration
Branch
4
Health
Effects
Division
(7509C)
TO:
Mark
T
Howard,
Chemical
Review
Manager
Reregistration
Branch
3
Special
Review
&
Reregistration
Division
(7508C)
Attached
is
HED's
revised
risk
assessment
of
the
insecticide,
lindane
for
purposes
of
issuing
a
Reregistration
Eligibility
Decision
(RED)
Document
for
this
active
ingredient.
This
document
revises
the
June
13,
2002
version
of
the
risk
assessment
to
incorporate
changes
to
the
residue
chemistry
and
occupational
exposure
sections
based
on
updated
information.
It
also
includes
technical
corrections
to
the
documentation
for
the
worker
exporsure
assessment.
This
assessment
incorporates
information
from
the
toxicology
assessment
conducted
by
Suhair
Shallal,
the
residue
chemistry
and
dietary
exposure
and
risk
assessments
conducted
by
Thurston
Morton,
and
the
occupational
and
residential
exposure
assessment
conducted
by
Dave
Jaquith.
The
disciplinary
science
chapters
and
other
supporting
documents
have
also
been
revised
in
response
to
public
comment
where
necessary
and
are
included
as
appendices
as
follows:
Revised
Report
of
the
Hazard
Identification
Assessment
Review
Committee.
Suhair
Shallal
(6/
18/
01,
014595)
Report
of
the
FQPA
Safety
Factor
Committee.
Brenda
Tarplee
(8/
2/
00;
014272)
Revised
Product
and
Residue
Chemistry
Chapter.
Thurston
Morton
(12/
11/
01,
D279259)
Toxicology
Chapter.
Suhair
Shallal
(9/
28/
00,
D269338)
Occupational
and
Residential
Exposure
Assessment.
David
Jaquith
(6/
4/
02,
D283397,
4/
23/
02,
D282419,
4/
24/
02,
D282418)
Revised
Dietary
Exposure
and
Risk
Estimates
for
Reregistration.
Thurston
Morton
(12/
13/
01,
D279260)
Dietary
Risk
and
Exposure
Estimate
for
Lindane
through
Subsistence
Diets
for
Indigenous
People
of
Alaska.
Thurston
Morton
(4/
17/
02,
D282455)
Environmental
Fate
and
Effects
Chapter.
Nicholas
Federoff
(12/
20/
01,
D254764;
5/
20/
02,
D281832)
2
Table
of
Contents
I.
EXECUTIVESUMMARY
..............................................
1A
UseandMajorFormulations
..........................................
1B
RegulatoryHistory
..................................................
1C
HazardIdentificationandDose
ResponseAssessment
.....................
2D
ExposureAssessment
................................................
4E
RiskAssessment/
Characterization
......................................
6II
PhysicalandChemicalProperties
.........................................
9III
Hazard
assessment
....................................................
9A
ToxicologyAssessment...............................................
9B
DoseResponseAssessment
...........................................
14i
DeterminationofSusceptibility.....................................
14ii
CancerClassification............................................
15iii
Toxicology
Endpoint
Selection
....................................
15iv
EndocrineDisruptorEffects
......................................
19v
IncidentReports
................................................
19IV
ExposureandRiskAssessment
.........................................
20A
DietaryExposure(
FoodSources)......................................
20i
Background.....................................................
20ii
SourcesofLindaneResiduesonFoods...............................
22iii
Residue
Chemistry
Studies
for
Lindane
.............................
22B
DietaryExposureEstimates
..........................................
27C
DietaryRiskEstimates(
FoodSources).................................
29i
AcuteDietaryExposureandRiskEstimates
..........................
29ii
ChronicDietaryExposureandRiskEstimates
........................
29iii
Chronic
Dietary
Exposure
and
Risk
Estimates
for
Indigenous
People
.....
30iv
CancerDietaryExposureandRiskEstimates
........................
30D
UncertaintiesinDietaryExposureAssessment
.............................
30E
DrinkingWaterExposure
...........................................
31i
MonitoringData
................................................
32ii
GroundWater
.................................................
32iii
Surface
Water
.................................................
33iv
DrinkingWaterEstimatedEnvironmentalconcentrations
..............
33F
DrinkingWaterRiskEstimates.......................................
34i
DWLOCsforChronicExposure
....................................
34ii
DWLOCforAcuteExposure......................................
35iii
Non
Dietary
Exposure
...........................................
36
3
G.
OccupationalExposureandRiskEstimates
.............................
36i
CommercialSeedTreatment.......................................
37ii
OnFarmSeedTreatment.........................................
38iiiOccupationalExposureandRisk
...................................
38V
AggregateandCumulativeExposureandRiskCharacterization...............
40A
AcuteAggregateRisk...............................................
41B
Short
andIntermediate
TermAggregateRisk...........................
41C
ChronicAggregateRisk
.............................................
41D
CumulativeExposureandRisk
.......................................
42VI
RiskCharacterization.................................................
43VII
DataNeeds
........................................................
46A
ToxicologyDataRequirements
.......................................
46B
Product
andResidueChemistryDataRequirements
......................
47
1
I.
EXECUTIVE
SUMMARY
A.
Use
and
Major
Formulations
Lindane
(gamma
isomer
of
hexachlorocyclohexane,
HCH)
is
a
broad
spectrum
organochlorine
insecticide/
acaricide
which
has
been
used
on
a
wide
range
of
soil
dwelling
and
plant
eating
(phytophagous)
insects.
Worldwide,
it
is
commonly
used
on
a
wide
variety
of
crops,
in
warehouses,
in
public
health
to
control
insect
borne
diseases,
and
(with
fungicides)
as
a
seed
treatment.
Lindane
is
also
presently
used
in
lotions,
creams,
and
shampoos
for
the
control
of
lice
and
mites
(scabies)
in
humans;
these
pharmaceutical
uses
are
regulated
by
FDA.
In
the
U.
S.,
the
only
registered
food/
feed
use
is
seed
treatment
for
field
and
vegetable
crops.
Lindane
may
be
found
in
formulations
with
a
host
of
fungicides
and
insecticides.
Labels
for
products
containing
it
must
bear
the
Signal
Word
WARNING.
Some
formulations
of
lindane
are
classified
as
Restricted
Use
Pesticides
(RUP),
and
as
such
may
only
be
purchased
and
used
by
certified
pesticide
applicators.
Lindane
is
no
longer
manufactured
in
the
U.
S.
According
to
a
REFS
search,
conducted
on
5/
29/
01,
there
are
approximately
34
federally
registered
end
use
products
(EPs)
containing
lindane
as
the
active
ingredient
and
three
Section
24
C
registrations.
Lindane
end
use
products
are
formulated
as
dust
(D),
wettable
powder
(WP),
emulsifiable
concentrate
(EC),
flowable
concentrate
(FlC),
and
ready
to
use
(RTU)
solution.
The
reregistration
of
lindane
is
being
supported
by
Centre
International
d'Etudes
du
Lindane
(CIEL)
and
its
member
company
holding
U.
S.
registrations,
Inquinosa,
S.
A.
Currently,
Inquinosa
does
not
have
any
registered
lindane
end
use
products.
In
1993,
CIEL
offered
to
voluntarily
cancel
all
crop
uses
of
lindane
except
seed
treatment
and
certain
non
food
uses.
The
Agency
considers
lindane
seed
treatment
as
a
food
use
requiring
tolerances
based
on
existing
data
from
radiolabeled
studies
indicating
uptake
of
residues
from
the
treated
seeds
into
the
aerial
portion
of
the
growing
crop.
B.
Regulatory
History
Lindane
is
a
List
A
reregistration
pesticide.
A
Reregistration
Standard
for
Lindane
was
issued
9/
85.
The
Residue
Chemistry
Chapter
to
the
Reregistration
Standard
was
issued
on
6/
7/
85,
an
addendum
on
9/
5/
85,
and
an
Update
on
1/
31/
91.
The
Reregistration
Standard
along
with
its
Science
Chapters
summarized
the
available
data
for
each
residue
chemistry
guideline
and
specified
what
additional
data
are
required
for
reregistration
purposes.
Data
Call
In
(DCI)
Notices
for
lindane
were
issued
by
the
Agency
on
9/
30/
91,
3/
3/
95,
10/
13/
95,
and
3/
31/
97.
The
information
contained
in
this
document
outlines
the
current
Residue
Chemistry
Science
Assessments
with
respect
to
supporting
seed
treatment
uses
of
lindane,
as
well
as
the
reregistration
of
the
pesticide.
In
1983,
EPA
concluded
a
major
Special
Review
effort
of
lindane
based
on
carcinogenicity,
fetotoxicity/
teratogenicity,
reproductive
effects,
and
acute
effects
on
aquatic
2
organisms.
This
effort
resulted
in
the
cancellation
of
indoor
uses
of
smoke
fumigation
devices
and
greatly
limited
the
use
of
pet
dips
on
dogs.
In
addition,
there
were
uses
that
were
allowed
to
continue
only
if
certain
imposed
restrictions
were
implemented.
The
restrictions
were
based
on
the
degree
of
associated
hazards,
and
included
changes
in
warning
labels,
the
wearing
of
protective
clothing,
and
restrictions
to
limit
uses
to
certified
pest
control
operators.
In
1995,
EPA
announced
(FR
Vol.
60,
No.
143,
38329
38331,
7/
26/
95)
its
decision
not
to
initiate
a
Special
Review
of
lindane
based
on
worker
health
concerns
arising
from
studies
showing
irreversible
renal
effects
in
the
rat.
The
Agency
has
determined
that
these
effects
occur
only
in
the
kidneys
of
male
rat
and
are
not
relevant
for
human
risk
assessment.
Tolerances
are
currently
established
under
40
CFR
§180.133
for
residues
of
lindane
per
se
in/
on
various
raw
agricultural
commodities
at
0.01
ppm
(pecans)
to
3
ppm
(cucumbers,
lettuce,
melons,
mushrooms,
pumpkins,
squash,
summer
squash,
and
tomatoes).
Lindane
tolerances
are
also
established
at
4
ppm
in
the
fat
of
meat
from
hogs
and
at
7
ppm
in
the
fat
of
meat
from
cattle,
goats,
horses,
and
sheep.
No
tolerances
have
been
established
for
processed
food/
feed
commodities.
Adequate
methods
are
available
for
the
enforcement
of
tolerances
for
residues
of
lindane
per
se
in/
on
plant
and
animal
commodities.
The
only
food/
feed
use
of
lindane
which
is
being
supported
for
reregistration
is
seed
treatment
on
cereal
grains
(excluding
rice
and
wild
rice).
Seed
treatment
uses
on
broccoli,
Brussels
sprouts,
cabbage,
cauliflower,
lettuce,
radishes,
and
spinach
are
no
longer
being
supported
for
reregistration
by
Inquinosa.
In
addition,
the
established
tolerances
for
the
following
commodities
will
be
revoked
because
no
registrants
have
committed
to
support
the
foreign
or
domestic
uses
for:
apples,
apricots,
asparagus,
avocados,
celery,
cherry,
collards,
cucumbers,
eggplants,
grapes,
guavas,
kale,
kohlrabi,
mangoes,
melons,
mushrooms,
mustard
greens,
nectarines,
okra,
onions
(dry
bulb
only),
peaches,
pears,
pecans,
peppers,
pineapple,
plums
(fresh
prunes),
pumpkins,
quinces,
squash,
strawberries,
summer
squash,
swiss
chard
and
tomatoes.
C.
Hazard
Identification
and
Dose
Response
Assessment
The
toxicology
database
for
lindane
is
complete
with
respect
to
the
OPPTS
Guideline
requirements.
In
acute
toxicity
studies,
lindane
is
a
moderately
toxic
compound,
EPA
toxicity
class
II.
It
is
neither
an
eye
irritant
nor
dermal
sensitizer.
The
toxicity
endpoints
used
in
this
document
to
assess
hazards
include
acute
dietary
and
chronic
dietary
reference
doses
(RfDs),
and
short,
intermediate
and
long
term
dermal
and
inhalation
no
observable
adverse
affect
levels
(NOAELs).
In
light
of
the
developing
Agency
policy
on
use
of
toxicology
studies
employing
human
subjects,
HED
selected
doses
and
endpoints
for
risk
assessment
based
solely
on
animal
studies.
The
primary
effect
of
lindane
is
on
the
nervous
system;
in
acute,
subchronic,
and
developmental
neurotoxicity
studies
and
chronic
toxicity/
oncogenicity
studies,
lindane
appears
to
3
cause
neurotoxic
effects
including
tremors,
convulsions
and
hypersensitivity
to
touch.
This
is
further
corroborated
by
the
published
literature
in
which
human
exposure
has
been
seen
to
produce
neurologic
effects.
Lindane
also
causes
renal
and
hepatic
toxicity
via
the
oral,
dermal
and
inhalation
routes
of
exposure
as
seen
in
subchronic,
2
generation
reproduction
and
chronic
toxicity
studies
in
the
rat,
as
well
as
in
studies
in
the
open
literature
(S.
Shallal,
D274510).
In
developmental
toxicity
studies,
developmental
effects
were
only
seen
at
levels
where
maternal
toxicity
was
also
evident.
In
the
rat
developmental
study,
the
developmental
effects
(extra
rib
and
total
skeletal
variations)
were
seen
at
dose
levels
(20
mg/
kg/
day)
greater
than
maternal
toxicity
(10
mg/
kg/
day).
In
the
reproductive
toxicity
study,
both
systemic
and
developmental
LOAELs
are
13
mg/
kg;
however
a
qualitative
difference
in
maternal
and
offspring
effects
(reduced
body
weight
of
maternal
animals
and
reduced
viability
and
delayed
maturation
in
pups)
indicates
an
increased
susceptibility
to
exposure.
This
is
further
corroborated
by
a
developmental
neurotoxicity
study
in
which
a
qualitative
and
quantitative
increase
in
susceptibility
is
seen.
At
the
high
dose
(13.7
mg/
kg/
day)
,
animals
in
the
F0
generation
have
a
reduced
body
weight
and
body
weight
gain
while
at
the
mid
dose
(5.6
mg/
kg/
day),
F1
animals
have
a
reduced
survival
rate,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation
as
compared
to
controls.
The
OPP/
Cancer
Assessment
Review
Committee
(CARC)
has
completed
the
review
of
newly
submitted
carcinogenicity
study
in
CD
1
mice
along
with
other
data.
In
accordance
with
the
EPA
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(July,
1999),
the
CARC
has
classified
lindane
into
the
category
"Suggestive
evidence
of
carcinogenicity,
but
not
sufficient
to
assess
human
carcinogenic
potential"
based
on
an
increased
incidence
of
benign
lung
tumors
in
female
mice
only.
The
Committee,
therefore,
recommended
that
the
quantification
of
human
cancer
risk
is
not
required.
(S.
Diwan,
11/
29/
01,
TXR
NO.
0050297)
The
International
Programme
on
Chemical
Safety
(IPCS,
1991)
states
that
lindane
does
not
appear
to
have
mutagenic
potential.
The
available
mutagenicity
studies
are
negative;
they
include
a
dominant
lethal
mutation
assay,
sister
chromatid
exchange
assay
and
mammalian
cell
culture
gene
mutation
in
V79
cells.
However,
these
studies
have
been
classified
as
unacceptable
by
EPA.
The
Food
Quality
Protection
Act
(FQPA)
Safety
Factor
Committee
evaluated
the
hazard
and
exposure
data
to
determine
if
the
10x
safety
factor
should
be
retained.
The
Committee
recommended
that
the
FQPA
safety
factor
be
reduced
to
3X
due
to
the
following
considerations:
1)
the
toxicology
data
base
is
complete;
2)
the
available
data
provide
no
indication
of
quantitative
or
qualitative
increased
susceptibility
in
rats
from
in
utero
exposure
to
lindane
in
the
prenatal
developmental
study;
3)
the
offspring
effects
seen
in
the
developmental
neurotoxicity
study
were
the
same
as
those
seen
in
the
two
generation
reproduction
study
(no
additional
functional
or
morphological
hazards
to
the
nervous
system
were
noted);
4)
adequate
actual
data,
surrogate
data,
and/
or
modeling
outputs
are
available
to
satisfactorily
assess
food
exposure
and
to
provide
a
screening
level
drinking
water
exposure
assessment;
5)
although
the
developmental
4
toxicity
study
in
rabbits
was
classified
unacceptable,
the
HIARC
concluded
that
a
new
study
is
not
required;
and
6)
there
are
currently
no
residential
uses.
A
new
developmental
study
is
not
required
because:
a)
the
developmental
toxicity
study
in
rabbits
and
rats
using
a
subcutaneous
route
of
administration
shows
no
developmental
effects
at
the
maternally
toxic
dose;
b)
the
skeletal
effects
observed
in
the
developmental
toxicity
study
in
rats,
with
gavage
as
the
route
of
administration,
are
within
historical
controls;
c)
more
severe
maternal
effects
are
seen
in
the
rabbit
study
with
subcutaneous
administration;
d)
the
rat
appears
to
be
the
more
sensitive
species
for
developmental
effects;
and
e)
a
developmental
neurotoxicity
study
has
already
been
submitted.
D.
Exposure
Assessment
The
HED
Metabolism
Assessment
Review
Committee
(MARC)
concluded
that
the
total
radioactive
residues
(TRRs)
should
be
used
for
risk
assessment
purposes
and
calculation
of
dietary
burdens,
pending
receipt
of
additional
metabolism
data
(T.
Morton,
8/
30/
00,
D267069).
The
ChemSAC
recommended
comparing
the
results
from
the
dietary
analysis
using
the
TRRs
with
the
results
from
a
dietary
analysis
based
on
feeding
studies.
Exposure
to
lindane
was
determined
by
using
the
ratio
(ppm
TRR/
ppm
lindane
parent).
The
results
from
the
dietary
analysis
using
the
feeding
study
results
and
adjusting
the
lindane
residues
by
the
above
ratio
are
summarized
in
this
assessment.
The
Biological
and
Economic
Analysis
Division
(OPP/
BEAD)
verified
the
registrant's
percent
market
share
estimate
for
lindane
(I.
Yusuf
email,
7/
17/
00).
A
canola
processing
study
for
lindane
was
recently
reviewed
(T.
Morton,
D269388,
5/
10/
01).
Lindane
was
not
detected
in
bleached/
deodorized
canola
oil
(<
0.005
ppm).
Therefore,
½
LOQ
(0.
0025
ppm)
was
used
as
the
residue
estimate
in
DEEM
and
the
DEEM™
adjustment
factor
was
set
to
1.
DEEM™
default
concentration
factors
(adjustment
factor
1)
were
used
for
all
other
commodities.
The
Indigenous
Peoples
of
the
Arctic
region
of
the
U.
S.
(Alaska)
rely
heavily
on
subsistence
diets
as
their
food
source.
Therefore,
it
is
considered
appropriate
for
the
Agency
to
perform
a
supplementary
dietary
risk
and
exposure
assessment
to
assess
the
risk
to
the
Indigenous
People
from
worldwide
use
and
manufacture
of
lindane.
The
dietary
risk
assessment
for
Indigenous
People
of
Alaska
for
Lindane
has
been
revised
to
incorporate
new
information
pertaining
to
subsistence
meat
intake
by
children.
(T.
Morton,
D282455,
4/
17/
02).
Using
the
limited
data
available,
we
have
extrapolated
from
this
information
and
knowledge
of
the
standard
diet
of
the
indigenous
people
of
Alaska
to
arrive
at
a
conservative
estimate.
The
data
used
in
this
assessment
is
based
on
actual
residues
found
in
animal
tissues
in
conjunction
with
typical
subsistence
diet
consumption
rates.
Because
factors
such
as
bioaccumulation
of
lindane
and
the
cumulative
effects
of
combinations
of
chemicals
which
act
through
a
common
mode
of
action
have
not
been
incorporated
into
this
assessment,
it
is
therefore
difficult
to
know
the
full
range
of
residue
to
which
indigenous
populations
may
be
exposed.
Lindane
does
not
occur
naturally
in
the
environment.
Once
released
it
can
partition
into
all
environmental
media.
Lindane
has
been
detected
in
air,
surface
water,
groundwater,
sediment,
soil,
ice,
snowpack,
fish
and
other
aquatic
organisms,
wildlife,
and
humans.
Lindane
has
been
5
found
in
pristine
environments;
the
pathway
for
contamination
is
varied
and
complex
depending
on
atmospheric
and
oceanic
circulation,
gas/
particle
partitioning,
and
solubility
of
the
substance
and
the
food
chain.
Monitoring
data
has
shown
that
Lindane
is
detectable
across
the
entire
North
American
continent,
from
Washington
D.
C.,
Denver,
Colorado,
and
the
Niagra
River
water
samples
to
air
samples
over
the
Adirondack
Mountains
in
New
York,
Newport
News,
Virginia
and
Ontario,
Canada,
as
well
as,
soil
samples
from
around
the
Great
Lakes
and
the
Gulf
of
Mexico.
The
Environmental
Fate
and
Effects
Division
(EFED)
evaluated
the
potential
for
lindane
to
contaminate
water.
The
presence
of
lindane
in
the
environment,
due
to
previous
widespread
agricultural
use,
is
well
documented
in
U.
S.
data
bases.
For
example,
In
the
U.
S.
EPA
STORET
data
base,
720
detections
in
ground
water
were
reported
between
the
years
1968
and
1995,
in
nearly
all
regions
of
the
country,
with
especially
high
numbers
of
detections
in
the
South
and
West.
For
these
720
detections,
the
median
and
mean
concentrations
were
0.01
and
11
µg/
L,
respectively.
For
surface
waters,
8775
detections
were
reported
with
median
and
mean
concentrations
of
0.005
and
0.
18
µg/
L.
STORET
Detections
were
reported
in
nearly
all
regions
of
the
conterminous
U.
S.
In
the
USGS
NAWQA
study,
lindane
was
detected
in
2.58%
of
surface
water
samples
(0.
67%
at
levels
greater
than
0.05
µ
g/
L,
maximum
concentration
reported
was
0.
13
µ
g/
L).
For
groundwater,
USGS
NAWQA
reported
a
detection
frequency
of
0.
1
%
(0.
07%
at
levels
greater
than
0.01
µ
g/
L,
maximum
concentration
reported
was
0.032
µ
g/
L).
EFED
models
were
used
to
calculate
estimated
environmental
concentrations
(EECs)
in
drinking
water
from
surface
water
and
groundwater
contaminated
with
lindane
as
a
result
of
seed
treatment
uses.
Wheat
and
canola,
which
have
the
highest
application
rate
in
terms
of
lbs
a.
i
per
acre
were
used
as
the
model
crop
scenarios.
The
Screening
Concentration
in
Ground
Water
(SCI
GROW)
model
was
used
to
estimate
concentrations
of
lindane
in
groundwater.
The
screening
model,
FQPA
Index
Reservoir
Screening
Tool
(FIRST),
was
used
to
estimate
surface
water
concentrations.
Occupational
exposure
scenarios
can
be
described
as
short
term
(1
7
days),
intermediate
term
(7
days
to
several
months),
and
long
term
or
chronic
(several
months
to
a
lifetime).
All
of
the
lindane
exposure
scenarios
are
appropriately
described
as
short
and
intermediate
term.
HED
has
determined
that
there
are
potential
exposures
to
mixers,
loaders,
applicators,
or
other
handlers
during
usual
use
patterns
associated
with
lindane.
Based
on
the
use
patterns
and
potential
exposures
described
above,
6
major
exposure
scenarios
were
identified
to
represent
the
extent
of
lindane
uses:
(1)
on
farm
seed
treatment
with
dry
formulation
open
system,
(2)
on
farm
seed
treatment
with
liquid
formulation
closed
system,
(3)
mixing/
loading
and
applying
liquid
with
commercial
seed
treatment
equipment,
(4)
bagging
and
otherwise
handling
treated
seeds,
(5)
cleaning/
maintaining
seed
treatment
equipment,
and
(6)
loading/
planting
treated
seeds.
Worker
exposure
data
for
lindane
were
required
since
one
or
more
toxicological
criteria
had
been
triggered.
Requirements
for
applicator
exposure
studies
are
addressed
by
Series
875
Group
A
(formerly
Subdivision
U
of
the
Pesticide
Assessment
Guidelines).
Three
lindane
specific
6
exposure
studies
have
been
used
to
estimate
exposure,
one
addressing
on
farm
treatment,
one
addressing
commercial
seed
treatment,
and
one
addressing
planting
of
treated
seed.
E.
Risk
Assessment/
Characterization
Dietary
(food
source)
Anticipated
residues
were
provided
for
all
commodities
and
used
when
calculating
the
dietary
risk
associated
with
lindane
for
the
RED
(DP
Barcode
D279260,
T.
Morton,
12/
13/
01).
Although
the
database
for
lindane
is
substantially
complete,
additional
data
are
needed
to
eliminate
the
uncertainties
associated
with
the
exposure/
risk
assessment.
The
anticipated
residue
values
are
the
best
estimates
HED
can
provide
using
the
residue
data
available
at
this
time.
These
values
have
an
inherent
uncertainty
associated
with
variations
in
analytical
methods,
geographical
representation
of
field
trials,
seasonal
variation
of
residue
levels,
use
of
TRR
from
metabolism
studies,
etc.
The
acute
dietary
exposure
analysis
was
a
tier
3
probabilistic
assessment.
In
both
acute
and
chronic
risk
assessments,
exposure
was
compared
to
a
population
adjusted
dose,
(PAD),
which
is
the
reference
dose
(RfD)
reflecting
application
of
the
FQPA
3X
safety
factor.
HED
considers
dietary
residue
contributions
greater
than
100%
of
the
PAD
to
be
of
concern.
The
dietary
assessment
was
conducted
using
percent
crop
treated
(%
CT)
and
total
radioactive
residues
(TRRs)
from
plant
metabolism
studies
and
from
poultry
and
ruminant
metabolism
studies.
A
second
dietary
assessment
was
conducted
which
incorporated
data
generated
from
poultry
and
ruminant
feeding
studies
which
provided
lindane
only
residue
values.
In
this
assessment,
an
average
lindane
only
residue
value
was
calculated
from
three
dose
levels
and
multiplied
by
the
ratio
of
TRR:
lindane
derived
from
the
corresponding
poultry
or
ruminant
metabolism
studies.
(Average
lindane
residue
from
feeding
study
X
TRR
from
metabolism
study/
lindane
residue
from
metabolism
study).
The
following
assessments
yielded
higher
percent
aPAD
and
cPAD
values
which
were
used
to
calculate
drinking
water
levels
of
comparison
(DWLOCs).
Acute
Dietary
(Food).
The
acute
dietary
analysis
for
lindane
was
conducted
using
the
Dietary
Exposure
Evaluation
Model
(DEEM™)
software.
Results
are
reported
as
a
percentage
of
the
acute
Population
Adjusted
Dose
(aPAD)
for
the
99.9
th
percentile
of
the
population.
Estimated
acute
dietary
exposure
is
below
HED's
level
of
concern
for
all
population
subgroups
at
the
99.9
th
percentile.
The
maximum
dietary
risk
estimate
is
17
%
of
the
acute
PAD
(%
aPAD)
for
the
population
subgroup
all
infants
and
7
%
of
the
aPAD
for
the
U.
S.
Population
when
the
feeding
studies
were
adjusted
using
the
metabolism
studies.
Chronic
Dietary
(Food).
The
chronic
dietary
analysis
for
lindane
was
conducted
using
the
DEEM™
software.
Results
are
reported
as
a
percentage
of
the
chronic
Population
Adjusted
Dose
(cPAD).
Estimated
chronic
dietary
risk
is
below
HED's
level
of
concern.
The
resulting
risk
estimates
are
3
%
of
the
chronic
PAD
(%
cPAD)
for
the
U.
S.
population
and
11
%
of
the
cPAD
for
children
1
6
years
of
age
(the
most
highly
exposed
population
subgroup.
The
remaining
7
population
subgroups
were
<6
%
of
the
cPAD
when
the
feeding
studies
were
adjusted
using
the
metabolism
studies.
Acute
Drinking
Water.
Acute
DWLOCs
were
calculated
based
on
the
acute
dietary
exposure
and
default
body
weights
and
water
consumption
figures.
The
EECs
for
surface
water
and
the
EECs
for
groundwater
were
less
than
the
acute
DWLOCs
for
all
sub
populations
indicating
that
acute
aggregate
exposure
to
lindane
in
food
and
water
is
less
than
HED's
level
of
concern.
Chronic
Drinking
Water.
Chronic
DWLOCs
were
calculated
based
on
the
chronic
dietary
(food)
exposure
and
default
body
weights
and
water
consumption
figures.
The
EECs
for
surface
water
and
groundwater
were
less
than
the
chronic
DWLOCs,
indicating
that
chronic
exposure
to
lindane
in
food
and
water
is
less
than
HED's
level
of
concern.
Special
Populations.
The
Indigenous
Peoples
of
the
Arctic
region
of
the
U.
S.
(Alaska)
rely
heavily
on
subsistence
diets
as
their
food
source.
Therefore,
HED
performed
a
revised
supplementary
chronic
dietary
risk
and
exposure
assessment
to
assess
the
risk
to
Indigenous
People
from
worldwide
use
and
manufacture
of
lindane
(T.
Morton,
D282455,
4/
17/
02).
Because
the
annual
harvest
rates
were
divided
by
365
to
obtain
daily
harvest
rates,
and
the
daily
intake
rates
were
used
in
the
assessment,
no
acute
dietary
exposure
analysis
was
conducted.
The
chronic
dietary
exposure
analysis
used
subsistence
food
harvest
amounts
and
total
HCH
residues
in
traditional
foods,
and
adjusted
the
HCH
exposure
to
obtain
lindane
exposure.
To
estimate
subsistence
food
intake
rates,
EPA
used
data
from
the
Alaska
Department
of
Fish
and
Game
Division
of
Subsistence
data
base.
This
data
base
provides
subsistence
food
harvest
amounts
for
nearly
180
Alaskan
communities
from
1990
2001.
Since
marine
mammals
represents
the
largest
portion
of
the
subsistence
harvest,
HED
used
the
community
with
the
highest
representative
seal
harvest,
the
community
with
the
highest
walrus
harvest,
and
the
community
with
the
highest
whale
harvest
to
estimate
subsistence
intake
rates.
Other
subsistence
food
sources
(e.
g.,
land
mammals,
other
marine
mammals,
fish,
and
birds)
from
the
corresponding
Alaskan
community
were
also
included
in
estimating
subsistence
intake.
The
combined
subsistence
food
source
exposures
from
Community
1
(the
community
with
highest
total
intake
of
the
three
communities)
amounts
to
0.282065
mg/
day
HCH.
Adjusting
total
HCH
to
obtain
lindane
only
exposure
yields
a
lindane
exposure
for
Community
1
of
0.
04231
mg/
day.
(Total
HCH
is
adjusted
by
factors
of
0.
15
and
0.03
since
lindane
represents
between
3
and
15%
of
total
HCH
residues).
Based
on
revised
exposure
estimates
and
assuming
a
male
adult
body
weight
of
70
kg,
the
chronic
dietary
risk
to
adult
male
Indigenous
People
ranges
from
0.000055
0.
0006
mg/
kg
body
weight/
day
which
is
between
3
and
38
%
of
the
cPAD.
This
is
below
HED's
level
of
concern
(cPAD
=
0.
0016
mg/
kg
bw/
day).
The
revised
estimate
of
chronic
dietary
risk
to
adult
female
Indigenous
People
(body
weight
of
60
kg)
ranges
from
0.000064
0.0007
mg/
kg
bw/
day
or
from
4
to
44
%
of
the
cPAD,
also
below
HED's
level
of
concern.
Assuming
a
child
body
weight
of
10
kg
and
adjusting
adult
intake
by
a
factor
of
0.53
to
account
for
adult
versus
child
subsistence
meat
intake,
the
revised
lindane
dietary
risk
estimates
for
8
children
1
6
years
from
subsistence
food
consumption
range
from
0.0002
0.
0022
mg/
kg
bw/
day
or
from
13
to
138%
of
the
cPAD.
For
children
7
12
years
old,
the
lindane
residue
amount
was
divided
by
29
kg
(7
12
year
body
weight)
to
obtain
the
%
cPAD
from
subsistence
foods.
The
resulting
range
of
lindane
dietary
risk
estimates
from
subsistence
food
consumption
for
children
712
is
4
to
48%
of
the
cPAD,
which
is
below
HED's
level
of
concern.
Residential
Risk
Estimates.
No
residential
exposure
scenarios
have
been
identified
for
pesticide
uses
of
lindane
and
therefore
no
risk
estimates
will
be
presented
in
this
document
for
non
occupational
exposure
to
lindane.
Occupational
Risk
Estimates.
The
Agency
has
refined
occupational
estimates
using
the
toxicological
endpoints
chosen
by
OPP's
Hazard
Identification
Assessment
Committee
(HIARC)
and
two
recent
worker
exposure
studies,
one
on
commercial
seed
treatment
and
one
on
handling
and
planting
of
treated
seeds,
and
The
FQPA
uncertainty
factor
of
3X
is
not
applicable
to
occupational
risk
assessments.
Resulting
risk
estimates
are
reported
as
Margins
of
Exposure
(MOEs),
and
compared
to
the
target
MOE,
which
is
100
for
all
lindane
occupational
exposure
scenarios.
The
Agency
has
determined
that
there
are
potential
exposures
to
mixers,
loaders,
applicators,
or
other
handlers
during
usual
use
patterns
associated
with
lindane.
The
exposure
scenario
descriptions
based
on
the
use
pattern
of
lindane
are
presented
in
Table
12.
The
daily
exposures,
as
well
as
the
resulting
short
and
intermediate
term
MOEs
are
presented
in
Table
13.
Short
and
intermediate
(if
applicable)
term
MOEs
were
calculated
for
dermal
and
inhalation
exposure
routes
for
a
total
of
6
worker
exposure
scenarios.
The
analysis
indicates
MOEs
of
concern
(MOE<
100)
for
the
following
exposure
scenarios/
pathways:
dermal
exposure
from
on
farm
seed
treatment;
inhalation
exposure
from
commercial
treatment
(mixing/
loading/
application)
of
canola
seed
at
both
high
and
low
end
rates
of
1.
5
and
0.
75
lb/
100
lb
seed;
and
inhalation
exposure
from
commercial
handling
of
canola
seed
treated
at
the
high
end
application
rate
of
1.
5
lb/
100
lb
seed.
All
other
exposure
scenarios
result
in
MOEs
that
are
not
of
concern
for
either
dermal
or
inhalation
exposure
pathways.
Dermal
MOEs
for
all
scenarios
range
between
9
and
119000.
Inhalation
MOEs
range
from
30
to
16000.
Aggregate
Exposure
and
Risk.
The
Agency
considered
aggregate
exposure
and
risk
estimates
for
residents
who
might
be
exposed
to
lindane
from
multiple
sources,
such
as
residential
use,
food,
and
water.
Since
no
residential
exposure
is
expected,
an
aggregate
risk
estimate
was
not
calculated.
9
Cl
Cl
Cl
Cl
Cl
Cl
II.
Physical
and
Chemical
Properties
The
chemical
structure
and
physical
properties
of
Lindane
are
given
below.
Empirical
Formula:
C6
H6
Cl6
Molecular
Weight:
290.9
CAS
Registry
No.:
58
89
9
PC
Code:
009001
Lindane
is
a
white
crystalline
solid
with
a
melting
point
of
112
113
C,
specific
gravity
of
1.85,
octanol/
water
partition
coefficient
(Kow
)
of
3135,
and
vapor
pressure
of
9.4
x
10
6
mm
Hg
at
20
C.
Lindane
is
slightly
soluble
in
water
(10
ppm
at
20
C)
and
in
most
organic
solvents,
including
acetone
and
aromatic
and
chlorinated
hydrocarbons.
Lindane
is
only
slightly
soluble
in
mineral
oils.
Lindane
is
stable
to
light,
heat,
air,
and
strong
acids,
but
decomposes
in
alkali
solutions
to
trichlorobenzenes
and
HCl.
Fate
studies
show
that
lindane
is
both
moderately
mobile
(mean
Koc
=
1368)
and
highly
persistent
(soil
half
life
of
2.
6
years).
It
is
resistant
to
photolysis
and
hydrolysis
(except
at
high
pH),
and
degrades
very
slowly
by
microbial
actions.
Degradates
are
predominantly
pentachlorocyclohexane,
1,2,4,
trichlorobenzene,
and
1,
2,
3
trichlorobenzene.
Also,
lindane
can
possibly
transform
to
the
alpha
and
beta
isomers
of
hexachlorocyclohexane
by
biological
and
phototransformation,
although
this
issue
remains
to
be
conclusively
resolved.
Metabolites
are
not
quantified
since
they
comprise
less
than
10%
of
the
total
residue;
they
are
also
found
in
rat
metabolism
studies
and
have
therefore
been
indirectly
evaluated
for
their
toxicologic
effects.
III.
Hazard
assessment
A.
Toxicology
Assessment
Based
on
available
information
to
date,
the
Agency
has
determined
that
the
adverse
effects
of
primary
concern
for
lindane
are
those
related
to
neurotoxicity.
Organochlorine
pesticides,
such
as
lindane,
are
known
to
cause
delayed
neurotoxic
effects.
Symptoms
include
a
number
of
clinical
signs
and
symptoms,
including
headaches,
dizziness,
nausea,
vomiting,
diarrhea
and
increased
urination,
blurred
vision,
labored
breathing,
muscle
paralysis,
slow
heart
rate,
respiratory
depression,
convulsions,
coma
and
even
death.
Numerous
toxicological
studies
using
laboratory
animals
are
available
addressing
most
of
these
toxicological
endpoints
for
lindane.
In
acute,
subchronic
and
developmental
neurotoxicity
studies,
it
was
found
to
cause
neurotoxic
effects
including
tremors,
convulsions,
decreased
motor
activity,
increased
10
forelimb
grip
strength,
hypersensitivity
to
touch,
hunched
posture
and
decreased
motor
activity
habituation.
There
also
appears
to
be
a
greater
susceptibility
to
exposure
by
offspring
compared
to
parental
animals
in
the
developmental
neurotoxicity
study.
Lindane
has
also
been
implicated
as
a
possible
endocrine
disruptor
in
birds,
mammals
and
possibly
fish.
Further
studies
to
ascertain
the
validity
of
such
evidence
is
necessary
to
make
informed
risk
assessment
decisions.
Lindane
is
distributed
to
all
organs
at
measurable
concentrations
within
a
few
hours
after
oral
administration.
The
highest
concentrations
are
found
in
adipose
tissue.
The
metabolism
of
lindane
is
initiated
through
one
of
several
pathways:
Dehydrogenation
leading
to
HCB,
dehydrochlorination
leading
to
formation
of
pentachlorocyclohexene,
dechlorination
leading
to
formation
of
tetrachlorohexene,
or
hydroxylation
leading
to
formation
of
hexachlorocyclohexanol.
Further
metabolism
leads
to
a
large
number
of
metabolites.
Lindane
is
converted
by
enzymatic
reactions,
mainly
in
the
liver.
Lindane
appears
to
affect
the
liver
and
kidney
in
male
rats
when
administered
through
the
oral,
dermal
or
inhalation
routes
of
exposure.
Kidney
lesions
in
males
indicative
of
alpha
2µ
globulin
accumulation
were
observed
in
animals
treated
with
10
ppm,
but
are
not
considered
relevant
to
human
health
risk
assessment
The
liver
effects
include:
incidence
of
periacinar
hepatocytic
hypertrophy
which
was
significantly
(p
0.01)
increased
in
male
and
female
rats
dosed
at
100
ppm
(4.
81
and
6.00
mg/
kg/
day,
respectively).
In
addition,
increased
liver
and
spleen
weights,
and
decreased
platelets
were
also
noted.
Lindane
is
not
considered
teratogenic
when
administered
orally
or
subcutaneously.
Developmental
toxicity
NOAELs
were
found
to
be
at
levels
equal
to
or
greater
than
maternal
NOAELs,
except
in
the
developmental
neurotoxicity
study.
The
developmental
neurotoxicity
LOAEL
was
5.6
mg/
kg/
day
(NOAEL
is
1.2
mg/
kg/
day)
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation
compared
to
a
maternal
toxicity
LOAEL
of
13.7
mg/
kg/
day
(NOAEL
is
5.6
mg/
kg/
day)
based
on
decreased
body
weight
gains,
decreased
food
consumption,
and
increased
reactivity
to
handling.
The
data
base
for
reproductive
toxicity
is
considered
complete.
Both
parental
and
offspring
LOAELs
are
13
mg/
kg;
however
there
is
a
qualitative
difference
in
the
severity
of
effects.
In
the
parental
animals,
toxicity
was
seen
in
the
form
of
reduction
in
body
weight
gain
during
gestation
while
offspring
toxicity
was
correlated
with
decreases
in
pup
viability
and
pup
body
weight
in
the
F1
and
F2
generations
as
well
as
delayed
maturation
in
the
F2
generation.
Evidence
for
quantitative
increase
in
susceptibility
could
not
be
ascertained
due
to
the
wide
spread
in
the
doses
tested.
The
OPP/
Cancer
Assessment
Review
Committee
(CARC)
has
completed
the
review
of
newly
submitted
carcinogenicity
study
in
CD
1
mice
along
with
other
data.
In
accordance
with
the
EPA
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(July,
1999),
the
CARC
has
classified
lindane
into
the
category
"Suggestive
evidence
of
carcinogenicity,
but
not
sufficient
to
assess
human
carcinogenic
potential"
based
on
an
increased
incidence
of
benign
lung
tumors
in
female
11
mice
only.
The
Committee,
therefore,
recommended
that
the
quantification
of
human
cancer
risk
is
not
required.
In
a
mammalian
cell
gene
mutation
assay
and
an
in
vivo
sister
chromatid
exchange
assay,
no
mutagenic
response
was
detected.
These
studies
were
classified
as
unacceptable
by
EPA.
The
open
literature
suggests,
however,
that
technical
grade
HCH
(hexachlorohexane;
6.
5%
HCH)
may
induce
some
mutagenic
activity
as
evidenced
in
a
dominant
lethal
mutation
assay
and
sister
chromatid
exchanges.
It
has
been
noted,
however,
by
the
IPCS
that
lindane
does
not
appear
to
have
a
mutagenic
potential.
The
acute
toxicity
studies
for
lindane
are
summarized
in
Table
1,
and
the
toxicology
profile
for
lindane
is
summarized
in
Table
2.
The
toxicology
database
required
to
support
the
Reregistration
of
lindane
is
essentially
complete.
All
required
toxicology
studies
have
been
submitted
and
reviewed
by
Agency
scientists.
Table
1.
Guideline
Acute
Toxicity
Studies
for
Lindane
STUDY
TYPE
MRID
CATEGORY
RESULT
81
1Acute
oral
rat
00049330
II
LD50
88
mg/
kg
males
91
mg/
kg
females
81
2
Acute
dermal
rabbit
00109141
II
LD50
1000
mg/
kg
males
900
mg/
kg
females
81
3
Acute
inhalation
rat
Acc.
263946
III
LC50
1.56
mg/
L
both
sexes
81
4
Eye
irritation
rabbit
Acc.
263946
III
PIS
=
0.6
no
corneal
involvement
irritation
cleared
after
24
hours
81
5
Dermal
irritation
rabbit
Acc.
262946
IV
PIS
=
0
not
an
irritant
81
6
Dermal
sensitization
g.
pig
Acc.
262946
NA
not
a
sensitizer
Table
2.
Guideline
Toxicology
Studies
for
Lindane
Guideline
No./
Study
Type
MRID
No.
year/
Classification
Results
870.3250
90
Day
dermal
toxicity
in
rabbit
41427601
1990
acceptable/
guideline
NOAEL
=
10
mg/
kg/
day
LOAEL
=
60
mg/
kg/
day
based
on
lesion
in
the
liver
in
males
and
females
and
adrenal
gland
weight
increases
in
males
870.3465
90
Day
inhalation
toxicity
in
rat
00255003
1983
acceptable/
guideline
NOAEL
=
0.
025
mg/
kg/
day
LOAEL
=
0.
13
mg/
kg/
day
based
on
transient
microscopic
lesions
in
the
kidney
and
increased
kidney
weights
in
the
males.
40873501
1988
acceptable/
guideline
NOAEL
=
0.
08
mg/
kg/
day
LOAEL
=
0.25
mg/
kg/
day
based
on
death
of
one
male
and
one
female
Table
2.
Guideline
Toxicology
Studies
for
Lindane
Guideline
No./
Study
Type
MRID
No.
year/
Classification
Results
12
870.3700a
Prenatal
developmental
in
rat
00062656
1976
(Subcutaneous)
unacceptable/
nonguideline
Maternal
NOAEL
=
5
mg/
kg/
day
LOAEL
=
15
mg/
kg/
day
based
on
reduced
body
weight
Developmental
NOAEL
=
>30
mg/
kg/
day
LOAEL
=
not
identified
42808001
1971
acceptable/
guideline
Maternal
NOAEL
=
5
mg/
kg/
day
LOAEL
=
10
mg/
kg/
day
based
on
reduced
body
weight
and
food
consumption
Developmental
NOAEL
=
10
mg/
kg/
day
LOAEL
=
20
mg/
kg/
day
based
on
skeletal
variation.
870.3700b
Prenatal
developmental
in
rabbit
00062658
1976
(Subcutaneous)
unacceptable/
nonguideline
Maternal
NOAEL
=
5
mg/
kg/
day
LOAEL
=
15
mg/
kg/
day
based
on
clinical
signs,
mortality,
reduced
body
weight
Developmental
NOAEL
15
mg/
kg/
day
LOAEL
=
not
identified
42808002
1971
unacceptable/
nonguideline
Maternal
NOAEL
20
mg/
kg/
day
LOAEL
=
not
identified
Developmental
NOAEL
20
mg/
kg/
day
LOAEL
=
not
identified
870.3800
Reproduction
and
fertility
effects
in
rat
42246101
1991
acceptable/
guideline
NOAEL
=
1.
7
mg/
kg/
day
;
0.
09mg/
kg/
day
LOAEL
=
13
mg/
kg/
day
based
on
reduced
body
weight;
1.7
mg/
kg/
day
based
on
increased
kidney
weight
and
2
globulin
accumulation
(not
relevant
for
humans)
NOAEL
for
reproductive
toxicity
=1.
7
mg/
kg/
day
(20
ppm)
LOAEL
for
reproductive
toxicity
=
13
mg/
kg/
day
(150
ppm)
based
on
reduced
pup
body
weights
and
decreased
viability
in
both
generations
and
delayed
maturation
of
the
F2
pups
870.4300
Carcinogenicity
mice
special
study
1987
see
below
literature
studies
870.4100a
Chronic
toxicity
rodents
870.4200
Carcinogenicity
rats
41094101
41853701
42891201
1993
acceptable/
guideline
NOAEL
=0.
6
mg/
kg/
day
LOAEL
=
4.8
mg/
kg/
day
;
6
mg/
kg/
day
based
on
periacinar
hepatocyte
hypertrophy,
increased
liver
and
spleen
weights,
and
decreased
platelets
no
evidence
of
carcinogenicity
870.5300
Gene
Mutation
Mammalian
Cell
00144500
1985
unacceptable/
uideline
negative
Table
2.
Guideline
Toxicology
Studies
for
Lindane
Guideline
No./
Study
Type
MRID
No.
year/
Classification
Results
13
870.5915
In
Vivo
Sister
Chromatid
Exchange
00024504
1984
unacceptable/
guideline
negative
870.5450
dominant
lethal
assay
00062657
unacceptable/
guideline
negative
870.6200a
Acute
neurotoxicity
screening
battery
in
rat
44769201
1999
acceptable/
guideline
NOAEL
=
6
mg/
kg/
day
;
20
mg/
kg/
day
LOAEL
=
20
mg/
kg/
day
(
)
based
on
increased
grip
strength
and
decreased
motor
activity.
60
mg/
kg/
day
(
)
based
on
tremors,
convulsions,
decreased
motor
activity
and
increased
grip
strength.
870.6200b
Subchronic
neurotoxicity
screening
battery
in
rat
44781101
1999
acceptable/
guideline
NOAEL
=
7.
9
mg/
kg/
day
;
7.
1
mg/
kg/
day
LOAEL
=
30.2
mg/
kg/
day
and
28.1
mg/
kg/
day
based
on
hypersensitivity
to
touch
and
hunched
posture.
870.6300
Developmental
neurotoxicity
in
rat
45073501
1999
acceptable/
guideline
Maternal
NOAEL
=
5.
6
mg/
kg/
day
LOAEL
=
13.7
mg/
kg/
day
based
on
decreased
body
weight
gains,
decreased
food
consumption,
and
increased
reactivity
to
handling.
Offspring
NOAEL
=
1.
2
mg/
kg/
day
LOAEL
=
5.6
mg/
kg/
day
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
870.7600
Dermal
penetration
40056107
1987
rat
40056108
1987
rabbit
acceptable/
guideline
18
%
absorption
at
10
hours
literature
studies
Feldmann,
RJ
and
HI
Maibach,
Percutaneous
penetration
of
some
pesticides
and
herbicides
in
man,
Toxicology
and
Applied
Pharmacology,
28:
126
132
(1974).
Non
guideline
~10%
absorption
in
humans
Table
2.
Guideline
Toxicology
Studies
for
Lindane
Guideline
No./
Study
Type
MRID
No.
year/
Classification
Results
14
Other:
Tumorigenic
responses
to
lindane
in
mice:
potentiation
by
a
dominant
mutation.
Special
study
dietary
administration
1987
NOAEL
=
not
identified
LOAEL
=
23
mg/
kg/
day
(160
ppm)
based
on
induction
of
tumors,
increased
liver
weights,
increased
enzyme
activity,
and
irreversible
Clara
cell
hyperplasia
in
lung
evidence
of
carcinogenicity
induction
of
liver
and
lung
tumors
in
the
agouti,
pseudoagouti
and
black
mouse
strains—
only
females;
only
0
and
160
ppm
Other
Literature
Studies
In
addition
to
the
developmental
and
reproduction
studies
submitted
to
the
Agency
to
fulfill
the
OPPTS
Guidelines,
HED's
Hazard
Identification
Assessment
Review
Committee
(HIARC)
evaluated
a
segment
of
the
extensive
body
of
information
published
in
the
open
literature
dealing
with
lindane.
These
studies
show
that
exposure
to
lindane,
both
transplacental
and
via
mother's
milk,
is
possible
and
that
such
exposure
may
result
in
adverse
developmental
effects
on
human
offspring.
According
to
Karmaus
et
al
(1995),
females
exposed
to
lindane
risk
having
offspring
with
reduced
birthweight
and
length.
Pompa
et
al
(1994)
has
also
been
able
to
show
that
transfer
of
lindane
and
pentachlorobenzene
from
mother
to
newborn
rabbits
can
occur.
Rivera
et
al
(1990)
found
that
early
postnatal
exposure
to
lindane
may
induce
behavioral
changes
in
developing
rats.
Evidence
of
reproductive
failure
and
fetotoxicity
in
mice
has
been
compiled
by
Sircar
et
al.
B.
Dose
Response
Assessment
i.
Determination
of
Susceptibility
There
was
evidence
of
qualitative
increased
susceptibility
in
the
rat
multi
generation
reproduction
study:
Both
parental
and
offspring
LOAELS
are
13
mg/
kg;
however
there
is
a
qualitative
difference
in
the
severity
of
effects.
In
the
parental
animals,
toxicity
was
seen
in
the
form
of
reduction
in
body
weight
gain
during
gestation
while
offspring
toxicity
was
correlated
with
decreases
in
pup
viability
and
pup
body
weight
in
the
F1
and
F2
generations
as
well
as
delayed
maturation
in
the
F2
generation.
Evidence
for
quantitative
increase
in
susceptibility
could
not
be
ascertained
due
to
the
wide
spread
in
the
doses
tested.
There
is
also
quantitative
increased
susceptibility
demonstrated
in
the
rat
developmental
neurotoxicity
study:
Maternal
toxicity
observed
at
120
ppm
(13.7
mg/
kg/
day,
LOAEL)
is
based
on
decreased
body
weight
gains,
decreased
food
consumption,
and
increased
reactivity
to
handling
(maternal
NOAEL
is
50
ppm;
5.
6
mg/
kg/
day).
Offspring
toxicity
was
observed
at
50
ppm
(5.
6
mg/
kg/
day,
LOAEL)
and
is
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation
(NOAEL
is
10
ppm;
1.
2
mg/
kg/
day).
15
The
offspring
effects
seen
in
the
developmental
neurotoxicity
study
were
the
same
as
those
seen
in
the
two
generation
reproduction
study
no
additional
functional
or
morphological
changes
in
the
nervous
system
were
noted.
In
the
open
literature,
lindane
is
found
in
mother's
milk
and
metabolites
of
lindane
have
been
shown
to
cross
the
placental
barrier.
The
Food
Quality
Protection
Act
(FQPA)
Safety
Factor
Committee
met
on
August
2,
2000
and
evaluated
the
hazard
and
exposure
data
to
determine
if
the
10x
safety
factor
should
be
retained
(Tarplee,
DOC
#
014272).
The
Committee
recommended
that
the
FQPA
safety
factor
be
reduced
to
3x
because:
1)
the
toxicology
data
base
is
complete;
2)
the
available
data
provide
no
indication
of
quantitative
or
qualitative
increased
susceptibility
in
rats
from
in
utero
exposure
to
lindane
in
the
prenatal
developmental
study;
3)
although
the
developmental
toxicity
study
in
rabbits
was
classified
unacceptable,
the
HIARC
concluded
that
a
new
study
is
not
required;
4)
the
offspring
effects
seen
in
the
developmental
neurotoxicity
study
were
the
same
as
those
seen
in
the
two
generation
reproduction
study;
and
5)
adequate
actual
data,
surrogate
data,
and/
or
modeling
outputs
are
available
to
satisfactorily
assess
food
exposure
and
to
provide
a
screening
level
drinking
water
exposure
assessment;
and
6)
there
are
currently
no
residential
uses.
ii.
Cancer
Classification
On
May
30,
2001,
the
HED
Cancer
Assessment
Review
Committee
(CARC)
met
to
evaluate
the
carcinogenic
potential
of
lindane.
At
this
meeting,
the
CARC
could
not
make
a
determination
of
the
carcinogenic
potential
of
lindane
because
the
NTP
studies
were
of
limited
value
and
it
was
uncertain
if
the
study
on
Agouti,
Pseudoagouti
and
Black
mice
with
limited
data
could
be
used
for
regulatory
purposes.
In
addition,
the
CARC
was
informed
that
new
histopathology
data
would
be
submitted.
The
Committee
also
requested
additional
information
including
results
of
a
90
day
subchronic
range
finding
study
in
CD
1
mice,
an
earlier
RfD
Committee
report
and
analyses
of
the
older
studies
on
lindane.
The
Committee
met
again
on
September
13,
2001
and
reevaluated
all
the
available
information/
data
including
the
old
and
the
newly
gathered
information
that
was
previously
not
available
for
review.
Based
on
the
most
recent
review
of
the
data
including
the
newly
submitted
carcinogenicity
study
in
CD
1
mice
and
in
accordance
with
the
EPA
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(July,
1999),
the
CARC
has
classified
lindane
into
the
category
"Suggestive
evidence
of
carcinogenicity,
but
not
sufficient
to
assess
human
carcinogenic
potential"
based
on
an
increased
incidence
of
benign
lung
tumors
in
female
mice
only.
The
Committee,
therefore,
recommended
that
the
quantification
of
human
cancer
risk
is
not
required.
iii.
Toxicology
Endpoint
Selection
The
Hazard
Identification
Committee
(HIARC)
met
on
June
13,
2000
to
evaluate
the
existing
toxicology
database
for
lindane
and
identify
toxicological
endpoints
and
dose
levels
of
concern
appropriate
for
use
in
risk
assessments
for
different
exposure
routes
and
durations,
and
assess/
reassess
the
reference
dose
(RfD).
HIARC
met
again
on
May
22,
2001
to
reconsider
the
16
endpoint
for
occupational
risk
assessment
for
the
inhalation
route
of
exposure.
Previously
the
endpoint
was
based
on
kidney
lesions
and
increased
kidney
weights
resulting
from
the
accumulation
of
alpha
2
globulin.
These
effects
have
been
deemed
not
relevant
for
human
risk
assessment.
The
conclusions
and
toxicology
endpoints
selected
for
dietary
and
non
dietary
risk
assessments
are
presented
in
Table
3
below.
The
critical
toxicology
study
for
acute
dietary
risk
assessment
is
the
acute
neurotoxicity
study
in
rats.
In
an
acute
oral
neurotoxicity
study,
groups
of
10
rats/
sex/
dose
were
administered
a
single
dose
of
lindane
by
gavage
at
concentrations
of
0
(control),
6,
20,
or
60
mg/
kg.
Functional
observational
battery
(FOB)
and
motor
activity
(MA)
testing
were
performed
prior
to
administration
and
within
3
hours
(time
of
peak
effect)
of
dosing
(day
0),
and
on
days
7
and
14
post
dose.
Body
weights
were
recorded
pre
test,
weekly
during
the
study
period
and
on
FOB
assessment
days.
Clinical
signs
were
recorded
at
least
once
daily.
At
study
termination
all
animals
were
sacrificed
and
fixed
by
whole
body
perfusion,
designated
tissues
of
the
nervous
system
were
processed
for
microscopic
neuropathological
evaluation.
The
NOAEL
for
neurotoxic
effects
was
found
to
be
6
mg/
kg
for
females
and
the
LOAEL
was
20
mg/
kg
based
on
increased
forelimb
grip
strength
and
decreased
grooming
behavior
and
motor
activity
(MA).
The
NOAEL
for
neurotoxicity
in
males
is
20
mg/
kg
and
the
LOAEL
for
males
is
60
mg/
kg
based
on
tremors,
convulsions,
decreased
MA,
and
increased
forelimb
grip
strength.
The
Uncertainty
Factor
includes
10x
for
inter
species
variation,
and10X
for
intra
species
extrapolation.
The
FQPA
safety
factor
is
reduced
to
3X.
Therefore,
the
acute
Population
Adjusted
Dose
(aPAD)
is
0.02
mg/
kg/
day
(NOAEL
of
6
mg/
kg/
day
÷
300
(UF
of
100
x
FQPA
factor
of
3).
The
acute
dietary
endpoint
for
the
general
population
was
considered
sufficiently
protective
for
the
subpopulation
of
females
13
50.
Although,
there
was
evidence
of
increased
susceptibility
in
the
DNT,
the
offspring
effects
were
not
attributable
to
a
single
dose.
A
separate
endpoint
for
this
subpopulation
was
therefore
not
identified.
The
critical
toxicology
study
for
chronic
non
cancer
dietary
risk
assessment
is
the
chronic
toxicity/
oncogenicity
study
in
rats.
In
this
chronic
toxicity/
oncogenicity
study,
lindane
was
administered
in
the
diet
to
groups
of
115
male
and
115
female
Wistar
rats
per
dose
at
concentrations
of
0,
1,
10,
100,
or
400
ppm
for
2
years.
Corresponding
delivered
doses
were
0,
0.05,
0.47,
4.81,
and
19.66
mg/
kg/
day,
respectively,
for
males
and
0,
0.
06,
0.59,
6.00,
and
24.34
mg/
kg/
day,
respectively,
for
females.
The
systemic
toxicity
LOAEL
for
male
and
female
rats
is
100
ppm
(4.
81
and
6.0
mg/
kg/
day,
respectively)
based
on
periacinar
hepatocyte
hypertrophy,
increased
liver
and
spleen
weights,
and
decreased
platelets.
The
systemic
toxicity
NOAEL
is
10
ppm
(0.
47
and
0.
59
mg/
kg/
day
for
males
and
females,
respectively).
The
Uncertainty
Factor
includes
10X
for
inter
species
variation,
and10x
for
intra
species
extrapolation.
The
FQPA
safety
factor
is
reduced
to
3X.
Therefore,
the
chronic
Population
Adjusted
Dose
(cPAD)
was
determined
to
be
0.0016
mg/
kg/
day
(NOAEL
of
0.
47
mg/
kg/
day
÷
300
(UF
of
100
x
FQPA
of
3).
For
occupational
assessment,
the
dermal
absorption
rate
for
lindane
was
estimated
to
be
approximately
10%
in
10
hours
of
exposure
in
humans.
The
HIARC
concurred
with
the
TES
17
committee
decision
(HED
Doc.
#
013460)
that
the
dermal
absorption
factor
is
10%
based
on
a
published
report
by
Feldman
and
Maibach
(Toxicology
and
Applied
Pharmacology
28,
126
132,
1974).
Table
3.
Doses
and
Toxicological
Endpoints
Selected
for
Risk
Assessment
of
Lindane
EXPOSURE
SCENARIO
DOSE
(mg/
kg/
day)
ENDPOINT
STUDY
TYPE/
MRID
Acute
Dietary
general
population
NOAEL=
6
mg/
kg
UF
=
100
LOAELis20
mg/
kgbased
on
increasedgrip
strength,
increased
motor
activity
Acute
Neurotoxicity
in
Rats/
44769201
Acute
RfD
=
0.
06
mg/
kg/
day
aPAD
=
0.
02
mg/
kg/
day
Chronic
Dietary
NOAEL=
0.
47
mg/
kg/
day
UF
=
300
LOAEL
is
100
ppm
(4.
81
mg/
kg/
day)
periacinar
hepatocyte
hypertrophy,
increased
liver/
spleen
weight,
decreased
platelets
Chronic
Feeding
and
Carcinogenicity
in
Rats
41094101,
41853701
42891201
Chronic
RfD
=
0.
0047
mg/
kg/
day
cPAD
=
0.0016
mg/
kg/
day
Short
Term
1
(Dermal)
NOAEL=
1.
2
mg/
kg/
day
LOAEL
is
50
ppm
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
Developmental
Neurotoxicity
Study
in
Rats
(oral)
45073501
Intermediate
Term
1
(Dermal)
NOAEL=
1.
2
mg/
kg/
day
LOAEL
is
50
ppm
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
Developmental
Neurotoxicity
Study
in
Rats
(oral)
45073501
Long
Term
1
(Dermal)
NOAEL=
0.
47
mg/
kg/
day
LOAEL
is
100
ppm
(4.
81
mg/
kg/
day)
periacinar
hepatocyte
hypertrophy,
increased
liver/
spleen
weight,
decreased
platelets
Chronic
Feeding
and
Carcinogenicity
in
Rats
41094101,
41853701
42891201
Dermal
Absorption
Factor
=
10%
Short
Term
1
(Inhalation)
0.13
mg/
kg/
day
(0.
5
mg/
m
3
)
based
on
clinical
signs
(diarrhea,
piloerection)
seen
at
day
14
and
continuing
for
20
days
90
Day
Inhalation
Toxicity
/
00255003
Intermediate
Term
1
(Inhalation)
0.13
mg/
kg/
day
(0.
5
mg/
m
3
)
LOAEL
is
5.
0
mg/
m
3
based
on
increased
kidney
weights
of
female
rats
and
bone
marrow
effects.
90
Day
Inhalation
Toxicity
/
00255003
Long
Term
2
(Inhalation)
N/
A
N/
A
N/
A
1
An
MOE
of
100
was
selected
2
Exposure
thru
this
route
for
this
duration
is
not
expected
18
The
Maibach
study
tested
12
pesticides
and
herbicides,
including
lindane,
on
human
subjects
(6
per
chemical)
to
quantify
their
dermal
penetration.
C
14
labeled
chemicals
were
applied
topically
(4
g/
cm
2
)
to
the
forearm
or
via
the
intravenous
route
(1
Ci).
Excretion
of
the
chemicals
was
then
monitored
by
collecting
and
analyzing
urine
samples
during
the
5
day
testing
period.
All
results
were
calculated
as
percent
of
the
injected
or
applied
dose.
Data
obtained
after
IV
dosing
was
used
to
correct
the
skin
penetration
data
for
incomplete
urinary
recovery.
Lindane
was
shown
to
have
a
penetration
factor
of
9.3%
±
3.
7
(SD).
The
critical
study
selected
for
short
and
intermediate
term
dermal
risk
assessment
was
the
Developmental
Neurotoxicity
Study
in
rats.
A
90
day
dermal
toxicity
study
in
rabbits
was
available;
the
NOAEL
was
10
mg/
kg/
day
and
the
LOAEL
was
60
mg/
kg/
day
based
on
hepatic
toxicity.
The
HIARC
did
not
consider
this
study
to
be
appropriate
for
risk
assessment
and
instead
selected
an
oral
endpoint
due
to:
1)
the
concern
for
developmental
effects
as
seen
in
pups
in
the
developmental
neurotoxicity
study,
2)
developmental
effects
are
not
evaluated
in
the
dermal
toxicity
study,
3)
the
dermal
toxicity
study
was
conducted
in
the
rabbit,
while
the
increased
susceptibility
was
seen
in
rat
pups
via
an
oral
route,
and
4)
this
endpoint
will
be
protective
of
dermally
exposed
workers.
For
developmental
toxicity,
the
NOAEL
was
1.
2
mg/
kg/
day
and
the
LOAEL
was
5.6
mg/
kg/
day
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
The
target
MOE
is
100
(10X
for
interspecies
variation
and
10X
for
intraspecies
variation)
for
occupational
exposure.
Since
an
oral
endpoint
was
selected,
a
10%
dermal
absorption
factor
will
be
used
for
route
to
route
extrapolation.
The
critical
study
selected
for
risk
assessment
for
long
term
dermal
exposure
was
the
Chronic
One
Year
Toxicity
Study
in
rats,
which
is
discussed
above.
The
systemic
toxicity
LOAEL
for
male
and
female
rats
is
4.
81
and
6.0
mg/
kg/
day,
respectively,
based
on
periacinar
hepatocyte
hypertrophy,
increased
liver
and
spleen
weights,
and
decreased
platelets.
The
systemic
toxicity
NOAEL
is
0.47
and
0.
59
mg/
kg/
day
for
males
and
females,
respectively.
The
target
MOE
is
100
(10X
for
interspecies
variation
and
10X
for
intraspecies
variation)
for
occupational
exposure.
Since
an
oral
endpoint
was
selected,
a
10%
dermal
absorption
factor
will
be
used
for
route
to
route
extrapolation.
The
critical
study
for
inhalation
risk
assessment
for
lindane
is
an
90
Day
Inhalation
Toxicity.
Lindane
was
administered
by
inhalation
to
groups
of
12
male
and
12
female
Wistar
rats
at
nominal
concentrations
of
0,
0.02,
0.10,
0.50,
or
5.0
mg/
m
3
,
6
h/
day
for
90
days.
Lindane
was
detected
in
the
brain,
liver,
fat,
and
serum
of
all
exposed
rats.
The
HIARC
established
a
NOAEL
of
0.5
mg/
m
3
for
this
risk
assessment
based
on
clinical
signs
(diarrhea
and
piloerection)
seen
at
day
14
after
exposure
and
continuing
for
20
days
at
the
highest
concentration
tested
(5
mg/
m
3
).
This
NOAEL
is
applicable
and
appropriate
only
for
short
term
exposure
risk
assessment
because
the
effects
were
seen
during
this
period
of
exposure.
For
intermediate
exposures,
the
NOAEL
is
0.5
mg/
m
3
(0.
13
mg/
kg)
based
on
increased
kidney
weights
and
bone
marrow
effects.
For
inhalation
risk
assessments
for
occupational
exposure,
the
target
MOE
is
100
(10X
for
19
intraspecies
variation
and
10X
for
interspecies
variation).
Long
term
inhalation
exposure
is
not
expected.
iv.
Endocrine
Disruptor
Effects
EPA
is
required
under
the
FFDCA,
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(including
all
pesticide
active
and
other
ingredients)
"may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(EDSTAC),
EPA
determined
that
there
was
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(EDSP).
v.
Incident
Reports
The
Agency
has
conducted
a
review
of
reported
poisoning
incidents
associated
with
human
exposure
to
lindane.
The
Agency
has
consulted
the
following
data
bases
for
the
poisoning
incident
data
on
the
active
ingredient
lindane:
Incident
Data
System,
Poison
Control
Center
Data
1993
through
1998,
California
Data
1982
through
1998,
and
the
National
Pesticide
Telecommunications
Network.
The
review
only
included
lindane
containing
products
currently
registered
for
use
as
a
seed
treatment.
Incidents
due
to
all
other
types
of
lindane
products
were
excluded.
No
incidents
were
located
related
to
seed
treatment
use
of
lindane.
None
of
the
cases
reported
to
Poison
Control
Centers
from
1993
through
1998
concerned
products
identified
as
being
used
for
seed
treatment.
However,
it
should
be
noted
that
nearly
one
third
of
the
exposures
involving
lindane
did
not
identify
a
specific
product,
but
rather
just
exposure
to
lindane.
Detailed
descriptions
of
eight
cases
submitted
to
the
California
Pesticide
Illness
Surveillance
Program
(1982
1998)
were
reviewed.
In
three
of
these
cases,
lindane
was
deemed
the
primary
cause
of
the
illness.
All
three
incidents
occurred
in
1984.
All
three
cases
involved
driving
and
filling
planter
hoppers
with
treated
cotton
seed.
Two
of
the
cases,
apparently
involved
in
the
same
operation,
were
both
treated
in
a
hospital
and
off
work
for
7
days.
The
third
case
was
not
treated
in
a
hospital
but
was
off
work
for
2
days.
Specific
symptoms
were
not
reported
for
any
of
these
three
cases.
The
National
Pesticide
Telecommunications
Network
did
not
report
on
incidents
specifically
related
to
lindane
use
for
seed
treatment.
Relatively
few
incident
of
illness
have
been
reported
due
to
lindane
used
for
seed
treatment;
therefore,
no
recommendations
can
be
made
based
on
the
few
incident
reports
available.
20
IV.
Exposure
and
Risk
Assessment
A.
Dietary
Exposure
(Food
Sources)
i.
Background
In
1993,
CIEL
offered
to
voluntarily
cancel
all
crop
uses
of
lindane
except
seed
treatment
and
certain
non
food
uses.
The
Agency
considers
lindane
seed
treatment
as
a
food
use
requiring
tolerances
based
on
existing
data
from
radiolabeled
studies
indicating
uptake
of
residues
from
the
treated
seeds
into
the
aerial
portion
of
the
growing
crop.
The
only
food/
feed
use
of
lindane
which
is
being
supported
for
reregistration
is
seed
treatment
on
cereal
grains
(excluding
rice
and
wild
rice).
Seed
treatment
uses
on
broccoli,
Brussels
sprouts,
cabbage,
cauliflower,
lettuce,
radishes,
and
spinach
are
no
longer
being
supported
for
reregistration
by
Inquinosa.
In
addition,
the
established
tolerances
for
the
following
commodities
will
be
revoked
because
no
registrants
have
committed
to
support
the
foreign
or
domestic
uses
for:
apples,
apricots,
asparagus,
avocados,
celery,
cherry,
collards,
cucumbers,
eggplants,
grapes,
guavas,
kale,
kohlrabi,
mangoes,
melons,
mushrooms,
mustard
greens,
nectarines,
okra,
onions
(dry
bulb
only),
peaches,
pears,
pecans,
peppers,
pineapple,
plums
(fresh
prunes),
pumpkins,
quinces,
squash,
strawberries,
summer
squash,
swiss
chard
and
tomatoes.
Tolerances
for
residues
of
lindane
in/
on
food
and
feed
commodities
are
currently
established
under
40
CFR
§180.133
and
are
expressed
in
terms
of
lindane
per
se.
The
nature
of
the
residue
in
plants
is
not
adequately
understood.
A
new
nature
of
the
residue
study
from
seed
treatment
are
required
for
cereal
grain.
The
nature
of
the
residue
in
poultry
and
ruminants
is
adequately
understood.
The
HED
Metabolism
Assessment
Review
Committee
(T.
Morton,
8/
30/
00,
D267069)
concluded
that
the
total
radiolabeled
residues
(TRRs)
should
be
used
for
risk
assessment
purposes
and
calculation
of
dietary
burdens,
pending
receipt
of
additional
metabolism
data.
Table
4.
Tolerance
Reassessment
Summary
for
Lindane.
Commodity
Tolerance
Listed
Under
40
CFR
(ppm)
Reassessed
Tolerance
(ppm)
Comment
Tolerance
Listed
Under
40
CFR
§180.133
Apples
1
Revoke
Not
being
supported
for
reregistration.
Apricots
1
Revoke
Not
being
supported
for
reregistration.
Asparagus
1
Revoke
Not
being
supported
for
reregistration.
Avocados
1
Revoke
Not
being
supported
for
reregistration.
Broccoli
1
Revoke
Not
being
supported
for
reregistration.
Table
4.
Tolerance
Reassessment
Summary
for
Lindane.
Commodity
Tolerance
Listed
Under
40
CFR
(ppm)
Reassessed
Tolerance
(ppm)
Comment
21
Brussels
sprouts
1
Revoke
Not
being
supported
for
reregistration.
Cabbage
1
Revoke
Not
being
supported
for
reregistration.
Cauliflower
1
Revoke
Not
being
supported
for
reregistration.
Lettuce
3
Revoke
Not
being
supported
for
reregistration.
Spinach
1
Revoke
Not
being
supported
for
reregistration.
Celery
1
Revoke
Not
being
supported
for
reregistration.
Collards
1
Revoke
Not
being
supported
for
reregistration.
Kale
1
Revoke
Not
being
supported
for
reregistration.
Kohlrabi
1
Revoke
Not
being
supported
for
reregistration.
Mustard
greens
1
Revoke
Not
being
supported
for
reregistration.
Swiss
chard
1
Revoke
Not
being
supported
for
reregistration.
Cherry
1
Revoke
Not
being
supported
for
reregistration.
Cucumbers
3
Revoke
Not
being
supported
for
reregistration.
Eggplants
1
Revoke
Not
being
supported
for
reregistration.
Fat
of
meat
from
cattle,
goats,
horses,
and
sheep
7
Revoke
Current
tolerances
are
based
on
direct
dermal
application.
The
need
for
livestock
tissue
tolerances
will
be
reevaluated
when
the
required
nature
of
the
residue
study
in
plants
is
submitted
Fat
ofmeat
from
hogs
4
Grapes
1
Revoke
Not
being
supported
for
reregistration.
Guavas
1
Revoke
Not
being
supported
for
reregistration.
Mangoes
1
Revoke
Not
being
supported
for
reregistration.
Melons
3
Revoke
Not
being
supported
for
reregistration.
Mushrooms
3
Revoke
Not
being
supported
for
reregistration.
Nectarines
1
Revoke
Not
being
supported
for
reregistration.
Okra
1
Revoke
Not
being
supported
for
reregistration.
Onions
(dry
bulb
only)
1
Revoke
Not
being
supported
for
reregistration.
Peaches
1
Revoke
Not
being
supported
for
reregistration.
Pears
1
Revoke
Not
being
supported
for
reregistration.
Pecans
0.01
Revoke
Not
being
supported
for
reregistration.
Peppers
1
Revoke
Not
being
supported
for
reregistration.
Pineapple
1
Revoke
Not
being
supported
for
reregistration.
Plums
(fresh
prunes)
1
Revoke
Not
being
supported
for
reregistration.
Pumpkins
3
Revoke
Not
being
supported
for
reregistration.
Quinces
1
Revoke
Not
being
supported
for
reregistration.
Squash
3
Revoke
Not
being
supported
for
reregistration.
Strawberries
1
Revoke
Not
being
supported
for
reregistration.
Summer
squash
3
Revoke
Not
being
supported
for
reregistration.
Table
4.
Tolerance
Reassessment
Summary
for
Lindane.
Commodity
Tolerance
Listed
Under
40
CFR
(ppm)
Reassessed
Tolerance
(ppm)
Comment
22
Tomatoes
3
Revoke
Not
being
supported
for
reregistration.
ii.
Sources
of
Lindane
Residues
on
Foods
The
only
food/
feed
use
of
lindane
which
is
being
supported
for
reregistration
is
seed
treatment
on
cereal
grains
(excluding
rice
and
wild
rice).
Seed
treatment
uses
on
broccoli,
Brussels
sprouts,
cabbage,
cauliflower,
lettuce,
radishes,
and
spinach
are
no
longer
being
supported
for
reregistration.
There
are
no
adequate
nature
of
the
residue
studies
for
plants
from
seed
treatment
application;
therefore,
a
new
metabolism
study
is
required
for
cereal
grain.
A
seed
treatment
metabolism
study
was
reviewed
by
HED;
although
it
was
deemed
inadequate
due
to
insufficient
characterization/
identification
of
the
radioactive
residues,
it
was
found
to
be
useful
in
the
determination
of
the
TRR
for
use
in
this
dietary
exposure
analysis.
The
corn
grain
and
forage
TRRs
were
translated
to
sorghum.
Secondary
residues
in
livestock
commodities
may
result
from
livestock
consuming
treated
food.
The
nature
of
the
residue
in
poultry
is
understood.
The
nature
of
the
residue
in
ruminants
is
adequately
understood
since
the
registrant
recently
submitted
the
required
data
(MRID
45224101,
45224102,
and
45277201)
to
upgrade
a
ruminant
metabolism
study
(MRID
44867104)
which
was
deemed
inadequate.
The
lindane
equivalent
residue
values
used
in
the
dietary
exposure
analyses
were
derived
using
a
ratio
of
total
radioactive
residue
divided
by
the
amount
of
lindane
present
in
the
metabolism
studies
(ruminant
and
poultry).
Thiswould
be
worstcase
estimatesince
we
areassuming
thatallofthe
TRRwould
be
residues
of
concern.
The
dietary
exposure
analyses
using
the
total
radioactive
residues
is
a
Tier
3
assessment
since
percent
crop
treated
was
used
in
the
analyses.
The
dietary
exposure
analyses
that
were
based
on
the
adjustment
of
the
lindane
residues
in
the
livestock
feeding
studies
is
a
Tier
3
assessment.
Percent
market
share
was
available
for
all
crops
included
in
the
analyses.
Since
lindane
is
registered
for
seed
treatments
only,
there
is
no
difference
in
the
percent
crop
treated
between
crops
grown
for
the
fresh
market
and
those
grown
for
processing.
A
processing
study
was
available
for
canola
only;
the
default
DEEM™
processing
factors
were
used
for
all
other
foods.
iii.
Residue
Chemistry
Studies
for
Lindane
A
tabular
summary
of
the
residue
chemistry
science
assessments
for
reregistration
of
lindane
is
presented
in
Table
A
of
the
Revised
Residue
Chemistry
Chapter
(T.
Morton,
D279259,
12/
11/
01).
When
end
use
product
DCIs
are
developed
(e.
g.,
at
issuance
of
the
RED),
all
end
use
product
labels
(e.
g.,
MAI
labels,
SLNs,
and
products
subject
to
the
generic
data
exemption)
should
be
amended
such
that
they
are
consistent
with
the
basic
producers'
labels.
A
30
day
plant
23
back
interval
for
leafy
vegetables
and
a
12
month
plant
back
interval
for
all
other
unregistered
crops
is
required
on
all
end
use
product
labels
for
lindane.
Nature
of
the
Residue
Plants
(GLN
860.1300):
The
qualitative
nature
of
lindane
residues
in
plants
reflecting
seed
treatment
is
inadequately
understood.
For
the
purpose
of
reregistration,
the
basic
registrants
are
required
to
conduct
new
plant
metabolism
studies
on
lindane.
These
studies
should
be
conducted
on
a
representative
cereal
grain,
as
the
registrants
have
indicated
that
the
only
food
uses
they
are
supporting
are
for
seed
treatment
of
these
crops.
The
new
studies
should
be
conducted
at
rates
which
insure
that
sufficient
14
C
residues
are
available
for
analysis.
Crop
samples
should
be
harvested
at
the
appropriate
stage.
Identification
of
14
C
residues
should
also
be
confirmed
using
more
than
one
method,
or
by
GC/
MS.
Nature
of
the
Residue
Animals
(GLN
860.1300):
No
direct
livestock
treatments
remain
registered.
Residues
of
lindane
may
occur
in
livestock
as
a
result
of
feeding
of
lindane
treated
feed
(secondary
residues).
The
qualitative
nature
of
the
residue
in
ruminants
is
adequately
understood.
The
basic
registrants
have
recently
submitted
additional
data
for
the
ruminant
metabolism
study
(MRID
44867104)
which
was
deemed
inadequate
but
upgradable.
To
upgrade
the
study,
the
registrant
was
required
to
identify
the
metabolite
labeled
LiV
in
goat
liver's
aqueous
phase
which
accounted
for
25.2
%
of
the
total
radioactivity
(0.57
ppm).
In
addition,
storage
stability
data
was
required.
The
registrant
has
recently
submitted
the
required
data
(MRID
45224101,
45224102,
and
45277201)
thus,
adequately
addressing
this
deficiency.
The
total
radioactive
residues
(TRR;
expressed
as
lindane
equivalents)
in
collected
samples
were
3.
46
ppm
in
fat,
2.
25
ppm
in
liver,
0.
48
ppm
in
kidney,
0.
20
ppm
in
muscle,
and
0.
20
ppm
in
milk.
The
parent,
lindane
was
the
major
residue
identified
in
all
goat
matrices.
The
qualitative
nature
of
the
residue
in
poultry
is
adequately
understood.
A
poultry
metabolism
study
(MRIDs
40271301
and
44405404),
submitted
by
the
registrants
in
response
to
the
9/
85
Lindane
Reregistration
Guidance
Document,
has
recently
been
upgraded
to
acceptable
status.
A
brief
summary
of
the
poultry
metabolism
study
follows.
Laying
hens
were
dosed
with
[
14
C]
lindane
at
levels
equivalent
to
1.2
ppm
or
120
ppm
in
the
diet
for
four
consecutive
days.
Radioactive
residues
accumulated
to
the
greatest
extent
in
fatty
tissues.
In
high
dose
hens,
TRR
levels
were
highest
in
fat
(96.98
ppm)
and
lowest
in
breast
muscle
(1.44
ppm).
TRR
levels
were
proportionally
less
in
tissues
of
low
dose
hens
(fat,
1.
26
ppm;
breast
muscle
0.
02
ppm).
In
eggs
of
high
dose
hens,
14
C
residues
peaked
on
Day
4
at
10.83
ppm
in
yolks
and
0.21
ppm
in
whites.
Lindane
was
the
major
residue
component
identified
and
accounted
for
approximately
95%
of
the
TRR
in
egg
yolks,
71
86%
of
the
TRR
in
muscle,
skin,
and
fat,
and
52%
of
the
TRR
in
liver.
Other
metabolites
that
were
identified
included:
1,2,4
trichlorobenzene;
1,3,5
trichlorobenzene
and
dichlorobenzene(
s);
tetrachlorobenzene
(either
1,2,4,5
or
1,2,3,4);
PCCH;
1,
2,
3,
4tetrachlorobenzene
tetrachlorocyclohexene;
1,2,3,4,5
pentachlorobenzene;
and
hexachlorocyclohexene.
The
results
of
the
ruminant
and
poultry
metabolism
studies
will
be
presented
to
HED's
MARC
for
determination
of
terminal
residue
of
concern
in
eggs,
milk,
and
animal
tissues
once
an
adequate
seed
treatment
metabolism
study
is
submitted.
If
the
Committee
determines
that
lindane
24
is
the
only
residue
of
concern
requiring
regulation,
then
the
existing
storage
stability
data
for
poultry
commodities,
the
analytical
method
used
for
data
collection,
and
the
poultry
feeding
study
will
be
upgraded
to
acceptable
status.
In
the
absence
of
acceptable
metabolism
studies,
the
HED
MARC
(T.
Morton,
8/
30/
00,
D267069)
concluded
that
the
total
radioactive
residues
should
be
used
for
risk
assessment
purposes
until
adequate
plant
metabolism
studies
are
submitted.
Residue
Analytical
Methods
(GLN
860.1340):
Adequate
methods
are
available
for
determination
of
residues
of
lindane
per
se
in/
on
plant
and
animal
commodities.
The
Pesticide
Analytical
Manual
(PAM)
Vol.
II
lists
Methods
I
and
II
for
the
analysis
of
mixed
isomers
of
1,2,3,4,5,6
hexachlorocyclohexane
in/
on
plant
and
animal
commodities.
Method
I
is
a
multiresidue
method
(see
"GLN
860.1360:
Multiresidue
Methods"
section)
for
chlorinated
compounds.
Method
II
is
based
upon
the
official
final
AOAC
method
(1990,
15th
edition
of
AOAC)
and
is
suitable
for
determining
residues
of
lindane
in/
on
AOAC
Group
I
nonfatty
foods
(vegetables
and
fruits),
dairy
products,
fish,
and
eggs.
The
stated
limit
of
detection
of
Method
II
is
0.05
ppm
for
most
commodities.
Because
the
nature
of
the
residue
in
plants
resulting
from
seed
treatment
uses
as
well
as
the
nature
of
the
residue
in
ruminants
have
not
been
delineated,
the
adequacy
of
the
available
analytical
methods
cannot
be
determined.
The
registrants
are
reminded
that
radiovalidation
of
enforcement
method(
s)
is
a
reregistration
requirement;
therefore,
representative
samples
from
the
requested
plant
and
ruminant
metabolism
studies
should
be
used
for
validation
and
analyzed
by
the
existing
or
proposed
enforcement
method(
s)
to
determine
whether
total
toxic
residues
are
extracted
from
weathered
samples.
Adequate
data
collection
methods
have
been
submitted
for
detection
of
lindane
per
se
in/
on
cucumbers
and
spinach.
The
analytical
procedures
for
detecting
lindane
in
cucumbers
and
spinach
are
essentially
the
same.
Based
on
acceptable
method
validation
recoveries,
the
Agency
has
deemed
the
GC/
ECD
method
to
be
adequate
for
determining
residues
of
lindane
per
se
in
nonfatty
crops.
A
GC/
MS
method
(SOP#
Meth
109)
entitled
"Determination
of
Lindane
in
Wheat
and
Canola
Matrices"
was
utilized
as
the
data
collection
method
in
a
recently
submitted
wheat
field
study.
Following
extraction
and
purification,
detection
and
quantitation
were
conducted
using
a
gas
chromatograph
equipped
with
a
mass
selective
detector
(GC/
MS).
The
LOQ
was
0.
005
ppm.
A
data
collection
method,
based
on
the
AOAC
method,
was
also
submitted
for
detection
of
lindane
per
se
in
eggs,
milk,
and
animal
tissues.
The
Agency
previously
required
an
EPA
method
validation
for
the
submitted
method
if
lindane
tolerances
for
lean
animal
tissues
were
to
be
established
because
the
AOAC
method
did
not
describe
techniques
which
the
registrant's
method
contained
(e.
g.,
gel
permeation
chromatography
and
rotary
evaporation).
The
FDA
method
now
utilizes
these
techniques;
therefore,
the
requirement
for
a
petition
method
validation
25
was
conditionally
waived
provided
HED's
MARC
determines
that
lindane
per
se
is
the
only
residue
of
concern
in
animal
commodities.
Multiresidue
Methods
(GLN
860.1360):
The
10/
99
PESTDATA
database
(PAM,
Vol.
I,
Appendix
I)
contains
data
concerning
the
applicability
of
multiresidue
methods
to
lindane.
Lindane
is
completely
recovered
(>
80%
recovery)
using
protocols
302
(Luke
method),
303
(Mills,
Onley,
and
Gaither
method),
and
304
(Mills
method)
for
fatty
and
non
fatty
foods.
Should
the
HED
MARC
determine
that
lindane
metabolites
other
than
the
parent
should
be
regulated,
the
Agency
will
require
the
registrants
to
submit
additional
multiresidue
methods
test
data
for
the
metabolites
of
concern.
Storage
Stability
Data
(GLN
860.1380):
The
specifics
of
reregistration
requirements
for
storage
stability
data
in
plants
and
animals
cannot
be
ascertained
until
an
acceptable
plant
metabolism
study
is
available,
and
the
HED
MARC
has
determined
the
terminal
residues
of
concern.
Assuming
that
lindane
per
se
is
the
terminal
residue
of
concern
and
provided
the
additional
temperature
information
is
submitted,
the
available
storage
stability
data
for
lindane
support
the
storage
conditions
and
intervals
of
samples
collected
from
existing
crop
field
trials
and
livestock
feeding
studies.
A
summary
of
available
storage
stability
data
for
lindane
per
se
is
summarized
below.
Raw
agricultural
and
processed
commodities:
Residues
of
lindane
per
se
are
relatively
stable
under
frozen
(
20
C)
storage
conditions
for
up
to
8
months
in/
on
cucumbers
and
spinach
and
for
approximately
14
months
in/
on
tomatoes
and
wheat
forage.
Lindane
residues
are
stable
in
wheat
grain,
wheat
hay,
and
wheat
straw
for
approximately
18
months
when
stored
under
frozen
conditions.
Lindane
residues
in
canola
seed
were
stable
for
up
to
6.
5
months
when
stored
under
frozen
conditions
(no
temperature
given).
Lindane
residues
were
stable
for
up
to
2
months
in
canola
oil
and
1.
5
months
in
canola
meal
when
stored
under
frozen
conditions
(no
temperature
given).
The
registrant
is
required
to
submit
additional
storage
stability
data
(temperature
logs)
specifying
the
storage
conditions
of
the
canola
storage
stability
samples.
Assuming
that
lindane
per
se
is
the
terminal
residue
of
concern,
these
data
support
the
storage
conditions
and
intervals
of
samples
collected
from
existing
crop
field
trials.
Animal
commodities:
Residues
of
lindane
per
se
are
relatively
stable
in
eggs,
milk,
and
edible
tissues
of
animals
stored
frozen
(
18
C)
for
up
to
9
months.
Assuming
that
lindane
per
se
is
the
terminal
residue
of
concern,
these
data
support
the
storage
conditions
and
intervals
of
samples
collected
from
existing
ruminant
and
poultry
feeding
studies.
Crop
Field
Trials
(GLN
860.1500):
A
translocation
study
(MRID
40431207)
formed
the
basis
for
food
use
classification
of
lindane
when
the
pesticide
is
applied
as
a
seed
treatment.
In
this
study,
[
14
C]
lindane
was
applied
as
a
seed
treatment
to
corn
(field
and
sweet),
mustard,
radish,
spinach,
sugar
beet,
and
wheat
at
approximately
1x
the
label
rate.
The
treated
seeds
were
then
planted
outdoors
in
55
gallon
drum
halves
and
allowed
to
grow
under
simulated
normal
agricultural
practices.
Samples
of
immature
and
mature
crop
commodities
were
analyzed
for
total
14
C,
and
some
fractions
were
extracted
with
hexane
and
analyzed
by
a
GC
method
for
total
26
lindane.
The
study
failed
to
adequately
identify
radioactive
residues
in/
on
all
commodities
grown
from
treated
seed.
Nonetheless,
with
the
possible
exception
of
wheat
grain
and
foliage,
residues
were
characterized
to
be
not
associated
with
biological
molecules
(e.
g.,
amino
acid,
sugar,
etc.)
that
have
incorporated
the
radiolabel.
Should
the
HED
MARC
determine
that
lindane
metabolites
other
than
the
parent
should
be
regulated,
the
Agency
will
require
the
registrants
to
submit
additional
crop
field
trial
data
for
all
residues
of
concern.
The
registrant
has
submitted
PP#
9F05057,
for
the
establishment
of
time
limited
tolerances
for
residues
of
lindane
per
se
in/
on
the
RACs
of
crops
for
which
seed
treatments
are
being
proposed.
The
petition
included
a
number
of
leafy
and
brassica
vegetables,
radish,
and
corn.
The
only
crop
in
this
petition
which
is
now
being
supported
by
the
registrant
is
corn.
A
revised
Section
F
is
required
deleting
all
other
crops
from
the
petition.
Tolerances
cannot
be
established
or
reassessed
until
an
adequate
plant
metabolism
study
for
cereal
grain
is
submitted.
The
registrants
have
also
submitted
PP#
9F6022,
for
the
establishment
of
tolerances
on
lindane
per
se
in/
on
canola
for
which
seed
treatment
is
being
proposed.
Tolerances
cannot
be
established
or
reassessed
until
an
adequate
plant
metabolism
study
and
additional
residue
data
are
submitted.
In
addition,
the
registrants
recently
submitted
acceptable
residue
data
reflecting
seed
treatment
on
wheat
RACs.
A
representative
formulation
(lindane
30
C
flowable)
was
applied
as
a
seed
treatment
to
wheat
at
0.52
oz.
ai/
cwt
(or
330
ppm
lindane
on
the
seed).
Following
treatment,
the
treated
seeds
were
planted
in
15
diverse
geographic
locations.
Wheat
forage
samples
were
collected
at
or
near
the
jointing
stage,
the
hay
samples
at
early
flower
to
soft
dough
stage,
and
the
grain
and
straw
samples
at
normal
harvest
maturity.
Residues
of
lindane
were
nondetectable
(<
0.005
ppm)
in/
on
all
treated
wheat
grain
and
straw
samples.
Residues
of
lindane
ranged
from
<0.005
ppm
(nondetectable)
to
0.
04
ppm
in/
on
treated
wheat
forage
and
from
<0.005
ppm
(nondetectable)
to
0.
02
ppm
in/
on
treated
wheat
hay.
Additional
residue
data
would
be
required
if
the
HED
MARC
determines
residues
of
concern
include
metabolites
of
lindane
in
addition
to
lindane
per
se.
Processed
Food/
Feed
(GLN
860.1520):
No
data
are
available
to
determine
whether
lindane
residues
of
concern
concentrate
in
the
processed
fractions
of
cereal
grains
following
seed
treatment.
A
processing
study
on
corn
is
required
for
the
purpose
of
reregistration.
A
processing
study
on
wheat
would
also
be
required
if
the
HED
MARC
determines
residues
of
concern
include
metabolites
of
lindane
in
addition
to
lindane
per
se.
At
this
time,
a
processing
study
for
wheat
processed
fractions
is
not
being
required
if
lindane
per
se
is
the
only
residue
of
concern
(S.
Funk,
10/
31/
95,
D213401).
In
1998,
the
U.
S.
Food
and
Drug
Administration
(FDA)
monitoring
program
analyzed
a
total
of
227
samples
of
milled
grain
products
for
lindane
residues
at
an
LOQ
of
0.
01
ppm.
Commodities
analyzed
included
flour
and
other
milled
products,
breakfast
foods,
and
baked
goods.
Lindane
was
not
detected
in
any
sample.
27
The
registrant
submitted
a
canola
processing
study
along
with
PP#
9F6022
where
lindane
residues
in/
on
canola
refined
oil,
canola
meal,
and
bleached/
deodorized
canola
oil
were
determined.
Lindane
in
canola
refined
oil
concentrated
by
a
factor
of
at
least
5.
2x.
Lindane
did
not
concentrate
in
canola
meal
and
bleached/
deodorized
canola
oil.
Meat,
Milk,
Poultry,
Eggs
(GLN
860.1480):
The
nature
of
the
residue
in
plants
is
not
understood.
Upon
receipt
of
the
requested
plant
metabolism
data,
the
Agency
will:
(i)
determine
the
adequacy
of
established
tolerances
for
animal
commodities;
(ii)
calculate
the
expected
dietary
intake
for
beef
cattle,
dairy
cattle,
and
swine;
and
(iii)
re
evaluate
the
need
for
additional
feeding
studies.
It
should
be
noted
that
ruminant
(M.
Kovacs,
9/
20/
88,
CB
No.
4037)
and
poultry
feeding
(G.
Otakie,
8/
31/
88,
RCB
No.
4034)
studies
are
available
assuming
that
lindane
per
se
is
the
only
residue
of
concern
in
animals.
Confined/
Field
Accumulation
in
Rotational
Crops
(GLN
860.1850
and
860.1900):
The
basic
registrants
have
submitted
a
confined
rotational
crop
study
which
was
deemed
unacceptable
and
not
upgradable
because
of
inadequate
characterization
and
identification
of
residues
due
to
significant
losses
of
organosoluble
residues
during
analysis.
Although
the
study
is
inadequate
and
the
application
rate
used
(0.75
lb
ai/
A)
greatly
exceeds
the
level
of
soil
residues
that
are
likely
to
result
from
seed
treatment
uses,
the
data
indicate
that
residues
of
lindane
persist
in
the
soil
and
can
be
taken
up
by
rotational
crops
at
intervals
up
to
one
year.
For
the
purpose
of
reregistration,
the
Agency
will
not
require
a
new
confined
rotational
crop
study
provided
the
registrants
propose
a
30
day
plantback
interval
for
leafy
vegetables
and
a
12
month
plantback
interval
for
all
other
unregistered
crops
on
all
end
use
product
labels
for
lindane
as
recommended
by
the
ChemSAC
(memo,
10/
5/
00).
Since
this
proposal
has
been
accepted
by
the
registrants,
then
limited
rotational
field
trial
data
will
not
be
required.
B.
Dietary
Exposure
Estimates
Lindane
acute
and
chronic
dietary
exposure
assessments
were
conducted
using
the
Dietary
Exposure
Evaluation
Model
(DEEM™)
software
Version
7.
73,
which
incorporates
consumption
data
from
USDA's
Continuing
Surveys
of
Food
Intake
for
Individuals
(CSFII),
1989
1992.
The
1989
92
data
are
based
on
the
reported
consumption
of
more
than
10,000
individuals
over
three
consecutive
days,
and
in
total
represent
more
than
30,000
unique
"person
days"
of
data.
Foods
"as
consumed"
(e.
g.,
apple
pie)
are
linked
to
raw
agricultural
commodities
and
their
food
forms
(e.
g.,
apples
cooked/
canned
or
wheat
flour)
by
recipe
translation
files
internal
to
the
DEEM
software.
Consumption
data
are
averaged
for
the
entire
US
population
and
within
population
subgroups
(e.
g.,
children
one
to
six
years
old)
for
chronic
exposure
assessment,
but
are
retained
as
individual
consumption
items
for
acute
exposure
assessment.
For
chronic
exposure
and
risk
assessment,
estimates
of
average
residues
for
foods
(e.
g.,
orange)
or
food
forms
(e.
g.,
orange
juice)
of
interest
are
multiplied
by
the
averaged
consumption
estimate
of
each
food/
food
form
of
each
population
subgroup.
Exposure
estimates
are
expressed
in
mg/
kg
body
weight/
day
and
as
a
percent
of
the
cPAD.
28
For
acute
exposure
assessments,
individual
one
day
consumption
data
are
used
on
an
individual
by
individual
basis.
The
reported
consumption
amounts
of
each
food
item
can
be
multiplied
by
a
residue
point
estimate
and
summed
to
obtain
a
total
daily
pesticide
exposure
for
a
deterministic
(Tier
1
or
Tier
2)
exposure
assessment,
or
"matched"
in
multiple
random
pairings
with
residue
values
and
then
summed
in
a
probabilistic
(Tiers
3&
4)
assessment.
The
resulting
distribution
of
exposures
is
expressed
as
a
percentage
of
the
aPAD
on
both
a
user
(i.
e.,
those
who
reported
eating
relevant
commodities/
food
forms)
and
a
per
capita
basis.
Seed
treatment
uses
on
broccoli,
Brussels
sprouts,
cabbage,
cauliflower,
lettuce,
radishes,
and
spinach
are
no
longer
being
supported
for
reregistration
by
Inquinosa.
Therefore,
revised
acute,
chronic
dietary
exposure
and
risk
analyses
have
been
conducted
with
these
commodities
removed
(T.
Morton,
12/
13/
01,
279260).
The
HED
Metabolism
Assessment
Review
Committee
concluded
that
the
total
radiolabed
residues
(TRRs)
should
be
used
for
risk
assessment
purposes
and
calculation
of
dietary
burdens,
pending
receipt
of
additional
metabolism
data
(T.
Morton,
8/
30/
00,
D267069).
The
HED
ChemSAC
recommended
comparing
the
results
from
the
dietary
exposure
analysis
using
the
TRRs
as
the
residue
input
with
results
from
a
second
dietary
exposure
analysis
using
lindane
residues
per
se
from
the
livestock
feeding
studies.
Exposure
to
lindane
was
determined
by
using
the
ratio
(ppm
TRR/
ppm
lindane
parent)
from
the
livestock
metabolism
studies.
Only
the
commodities
being
supported
by
the
registrant
were
included
in
the
dietary
exposure
analysis;
no
import
uses
were
included
as
all
of
these
tolerances
will
be
revoked.
Additionally,
FDA
monitoring
data
show
that
residues
of
lindane
are
not
being
found
in
imported
commodities.
Some
residues
are
reported
for
gamma
BHC
but
these
residues
are
associated
with
use
of
BHC,
not
lindane.
The
Biological
and
Economic
Analysis
Division
(OPP/
BEAD)
verified
the
registrant's
percent
market
share
estimate
for
lindane
(I.
Yusuf
email,
7/
17/
00).
A
canola
processing
study
for
lindane
was
recently
reviewed
(T.
Morton,
D269388,
5/
10/
01).
Lindane
was
not
detected
in
bleached/
deodorized
canola
oil
(<
0.005
ppm).
Therefore,
½
LOQ
(0.
0025
ppm)
will
be
used
as
the
DEEM™
adjustment
factor
1.
DEEM™
default
concentrations
factors
(adjustment
factor
1)
will
be
used
for
all
other
concentration
factors.
The
wheat
grain
and
forage
TRRs
were
translated
to
barley,
oats,
and
rye.
The
corn
grain
and
forage
TRRs
were
translated
to
sorghum.
Anticipated
residues
(DP
Barcode
D279260,
T.
Morton,
12/
13/
01)
were
provided
for
all
commodities
and
have
been
used
when
calculating
the
dietary
risk.
Although
the
database
for
lindane
is
substantially
complete,
additional
data
are
needed
to
eliminate
the
uncertainties
associated
with
the
exposure/
risk
assessment.
The
anticipated
residue
values
are
the
best
estimates
the
Agency
can
provide
using
the
residue
data
available
at
this
time.
These
values
have
an
inherent
uncertainty
associated
with
variations
in
analytical
methods,
geographical
representation
of
field
trials,
seasonal
variation
of
residue
levels,
etc.
29
C.
Dietary
Risk
Estimates
(Food
Sources)
The
only
food/
feed
use
of
lindane
which
is
being
supported
for
reregistration
is
seed
treatment
cereal
grains
(excluding
rice
and
wild
rice).
Seed
treatment
uses
on
broccoli,
Brussels
sprouts,
cabbage,
cauliflower,
lettuce,
radishes,
and
spinach
are
no
longer
being
supported
for
reregistration.
A
revised
DEEM™
analysis
was
performed
to
estimate
acute
and
chronic
dietary
exposure
and
risk
from
lindane
from
all
commodities
supported
for
reregistration,
i.
e.,
seed
treatment
of
cereal
grains
(T.
Morton,
12/
13/
01,
D279260).
The
HED
Metabolism
Assessment
Review
Committee
concluded
that
the
TRRs
should
be
used
for
risk
assessment
purposes
and
calculation
of
dietary
burdens,
pending
receipt
of
additional
metabolism
data
(T.
Morton,
D267069,
8/
30/
00).
Results
of
the
dietary
exposure
analysis
are
presented
in
Table
5.
i.
Acute
Dietary
Exposure
and
Risk
Estimates
For
lindane,
the
acute
dietary
exposure
analysis
was
a
tier
3
probabilistic
assessment.
Estimated
acute
dietary
exposure
is
below
HED's
level
of
concern
for
all
population
subgroups
at
the
99.9
th
percentile.
The
maximum
dietary
risk
estimate
is
17
%
of
the
aPAD
for
the
subpopulation
all
infants
and
7
%
of
the
aPAD
for
the
U.
S.
population
when
the
feeding
studies
were
adjusted
to
include
all
lindane
related
residues
using
the
metabolism
studies.
ii.
Chronic
Dietary
Exposure
and
Risk
Estimates
Estimated
chronic
dietary
risk
is
below
HED's
level
of
concern.
The
resulting
risk
estimates
are
3
%
of
the
cPAD
for
the
U.
S.
population
and
11
%
of
the
cPAD
for
children
1
6
years
of
age
(the
most
highly
exposed
population
subgroup).
The
remaining
population
subgroups
were
<6
%
of
the
cPAD
when
the
feeding
studies
were
adjusted
to
include
all
lindane
related
residues
using
the
metabolism
studies.
Table
5.
Estimated
Acute
and
Chronic
Dietary
Exposure
and
Risk
Population
Subgroup
Acute
(99.
9th
%ile)
Chronic
(mean
exposure)
Exposure
(mg/
kg/
day)
%
aPAD
Exposure
(mg/
kg/
day)
%
cPAD
U.
S.
Population
0.
001305
7
0.
000054
3
All
infants
(<
1
yr)
0.003320
17
0.000072
5
Children
(1
6
yrs)
0.
001973
10
0.000173.
11
Children
(7
12
yrs)
0.001088
5
0.
000096
6
Females
(13
50
yrs)
0.000467
2
0.
000034
2
Males
(13
19
yrs)
0.000670
3
0.
000061
4
Males
(20+
yrs)
0.000458
2
0.
000034
2
Seniors
(55+
yrs)
0.000409
2
0.
000030
2
30
iii.
Chronic
Dietary
Exposure
and
Risk
Estimates
for
Indigenous
People
The
Indigenous
Peoples
of
the
Arctic
region
of
the
U.
S.
(Alaska)
rely
heavily
on
subsistence
diets
as
their
food
source.
HED
performed
a
revised
supplementary
chronic
dietary
risk
and
exposure
assessment
to
assess
the
risk
to
Indigenous
People
from
worldwide
use
and
manufacture
of
lindane
(T.
Morton,
D282455,
4/
17/
02).
Because
the
annual
harvest
rates
were
divided
by
365
to
obtain
daily
harvest
rates,
and
the
daily
intake
rates
used
in
the
assessment
no
acute
dietary
exposure
analysis
was
conducted.
The
chronic
analysis
used
subsistence
food
harvest
amounts,
total
HCH
residues
in
traditional
foods,
and
adjusting
the
HCH
exposure
to
obtain
lindane
exposure.
Based
on
revised
exposure
estimates,
the
chronic
dietary
risk
to
adult
male
Indigenous
People
ranges
from
0.000055
0.
0006
mg/
kg
body
weight/
day
which
is
between
3
and
38
%
of
the
cPAD.
This
is
below
HED's
level
of
concern
(cPAD
=
0.
0016
mg/
kg
bw/
day).
The
revised
estimate
of
chronic
dietary
risk
to
adult
female
Indigenous
People
ranges
from
0.000064
0.
0007
mg/
kg
bw/
day
or
from
4
to
44
%
of
the
cPAD,
also
below
HED's
level
of
concern.
The
revised
lindane
dietary
risk
estimates
for
children
resulting
from
subsistence
food
consumption
range
from
0.0002
0.
0022
mg/
kg
bw/
day
or
from
13%
to
138%
of
the
cPAD.
For
children
7
12
years
old,
the
lindane
residue
amount
was
divided
by
29
kg
(7
12
year
body
weight)
to
obtain
the
%
cPAD
from
subsistence
foods.
The
resulting
range
of
lindane
dietary
risk
estimates
from
subsistence
food
consumption
for
children
7
12
is
4
to
48%
of
the
cPAD.
Table
6.
Assumed
Total
Dietary
Intake
of
Lindane
(gamma
HCH)
and
Estimated
Chronic
Dietary
Risk
for
Indigenous
Peoples
Population
Subgroup
Body
Weight
(kg)
Lindane
Exposure
(mg/
kg/
day)
%
cPAD
Adult
male
70
0.
000055
0.
0006
3
38
Adult
female
60
0.
000064
0.
00071
4
44
Children
1
6
10
0.0002
0.
0022
13
138
Children
7
12
29
0.
00007
0.0008
4
48
iv.
Cancer
Dietary
Risk
Estimates
No
dietary
cancer
risks
for
lindane
were
estimated.
D.
Uncertainties
in
Dietary
Exposure
Assessment
There
are
no
adequate
nature
of
the
residue
metabolism
studies
for
plants
from
seed
treatment
application.
New
metabolism
studies
are
required
for
three
crops;
however,
a
seed
treatment
metabolism
study
(which
was
classified
as
inadequate)
was
reviewed
by
the
Agency
and
used
in
the
determination
of
the
TRR
for
use
in
this
dietary
exposure
analysis.
The
corn
grain
and
forage
TRRs
were
translated
to
sorghum.
The
nature
of
the
residue
in
poultry
and
ruminants
is
understood.
The
magnitude
of
the
residue
studies
in
poultry
and
cattle
only
analyzed
for
lindane
per
se.
The
total
residue
equivalents
were
derived
using
a
ratio
of
total
radioactive
residue
31
divided
by
the
amount
of
lindane
present
in
the
metabolism
studies.
This
would
be
worst
case
estimate
since
we
are
assuming
that
all
of
the
TRR
would
be
residues
of
concern.
The
dietary
exposure
analyses
using
the
total
radioactive
residues
is
a
Tier
3
probabilistic
assessment
since
percent
crop
treated
was
used
in
the
analyses.
Percent
market
share
was
available
for
all
crops
included
in
the
analyses.
Since
lindane
is
registered
for
seed
treatments
only,
there
is
no
difference
in
the
percent
crop
treated
values
between
crops
grown
for
the
fresh
market
and
those
grown
for
processing.
A
processing
study
was
available
for
canola
only;
the
default
DEEM™
processing
factors
were
used
for
all
other
foods.
E.
Drinking
Water
Exposure
Although
the
only
current
agricultural
use
of
lindane
is
for
seed
treatment,
lindane
has
been
extensively
used
in
the
past
as
an
insecticide
on
a
variety
of
crops,
for
home
termite
control,
and
as
a
wood
preservative.
Fate
studies
show
that
lindane
is
both
moderately
mobile
(mean
Koc
=
1368)
and
highly
persistent
(soil
half
life
of
2.
6
years).
Even
considering
lindane's
very
low
use
rate
under
the
current
use
restriction
to
seed
treatment
(maximum
of
0.
05
lb
a.
i./
acre),
modeling
studies
show
that
lindane
concentrations
in
both
surface
and
ground
water
may
reach
environmentally
significant
levels
(>
MCL).
This
conclusion
is
based
solely
on
lindane's
use
as
a
seed
treatment
and
does
not
consider
past
uses
of
lindane.
However,
note
that
lindane
continues
to
persist
in
the
environment
from
past
uses.
Lindane
is
persistent
and
moderately
mobile.
It
is
resistant
to
photolysis
and
hydrolysis
(except
at
high
pH),
and
degrades
very
slowly
by
microbial
actions.
Degradates
are
predominantly
isomers
of
benzene
hexachloride,
pentachlorocyclohexane,
1,2,4,
trichlorobenzene,
and
1,
2,
3
trichlorobenzene.
Also,
lindane
can
possibly
transform
to
the
alpha
and
beta
isomers
of
hexachlorocyclohexane
by
biological
and
phototransformation,
although
this
issue
remains
to
be
conclusively
resolved.
Metabolites
are
not
quantified
since
they
comprise
less
than
10%
of
the
total
residue;
they
are
also
found
in
rat
metabolism
studies
and
have
therefore
been
evaluated
for
their
toxicologic
effects.
Lindane
is
transported
through
the
environment
by
both
hydrologic
and
atmospheric
means.
Lindane
has
often
been
detected
in
surface
and
ground
water,
and
lindane
and
its
isomers
have
been
detected
in
areas
of
non
use
(e.
g.,
the
arctic),
indicating
global
atmospheric
transport.
Most
of
these
detections
resulted
from
a
combination
of
lindane's
past
widespread
use
and
its
extreme
persistence.
Currently,
U.
S.
agricultural
uses
of
lindane
are
restricted
to
seed
treatments,
and
application
rates
are
quite
low.
Even
under
these
restriction,
however,
lindane
may
reach
water
resources
at
levels
above
the
MCL
of
0.
2
µg/
L.
32
i.
Water
Monitoring
Data
The
presence
of
lindane
in
the
environment,
due
to
previous
widespread
agricultural
use,
is
well
documented
in
U.
S.
data
bases.
For
example,
In
the
U.
S.
EPA
STORET
data
base,
720
detections
in
ground
water
were
reported
between
the
years
1968
and
1995,
in
nearly
all
regions
of
the
country,
with
especially
high
numbers
of
detections
in
the
South
and
West.
For
these
720
detections,
the
median
and
mean
concentrations
were
0.01
and
11
µg/
L,
respectively.
For
surface
waters,
8775
detections
were
reported
with
median
and
mean
concentrations
of
0.005
and
0.
18
µg/
L.
STORET
Detections
were
reported
in
nearly
all
regions
of
the
conterminous
U.
S.
In
the
USGS
NAWQA
study,
lindane
was
detected
in
2.58%
of
surface
water
samples
(0.
67%
at
levels
greater
than
0.05
µ
g/
L,
maximum
concentration
reported
was
0.13
µ
g/
L).
For
groundwater,
USGS
NAWQA
reported
a
detection
frequency
of
0.
1
%
(0.07%
at
levels
greater
than
0.01
µ
g/
L,
maximum
concentration
reported
was
0.032
µ
g/
L).
Mean
and
median
concentrations
from
monitoring
data
are
below
HED's
calculated
Drinking
Water
Levels
of
Comparison
(See
Tables
10
and
11).
ii.
Ground
Water
EFED
used
the
Screening
Concentration
in
Ground
Water
(SCI
GROW)
model
to
estimate
lindane
concentrations
in
groundwater
contaminated
by
terrestrial
uses.
SCI
GROW
is
a
regression
based
model
that
uses
few
input
parameters:
pesticide's
organic
carbon
partition
coefficient
(Koc
),
aerobic
soil
degradation
half
life,
and
product
label
application
rate
and
frequency
(Barrett,
1997).
It
provides
a
groundwater
screening
concentration
for
use
in
determining
potential
risk
to
human
health
from
drinking
water
contaminated
with
a
pesticide.
The
groundwater
concentration
is
estimated
based
on
the
maximum
application
rates
in
areas
where
groundwater
is
exceptionally
vulnerable
to
contamination.
These
vulnerable
areas
are
characterized
by
high
rainfall,
rapidly
permeable
soil,
and
shallow
aquifer.
Input
parameters
and
output
and
the
resulting
EEC
are
summarized
in
Table
7.
Table
7.
SCIGROW/
Groundwater
Input
Parameters
and
Results
for
Seed
Treatment
Application
Rate:
Wheat
Canola
1
@
0.
051
lb/
acre
1
@
0.
116
lb/
acre
Aerobic
Soil
Half
Life
980
days
(mean
value)
Organic
Carbon
Partitioning
Coefficient
(Koc
)
1367
mL/
g
(median
value)
Peak
EEC
0.011
µg/
L
(wheat)
0.025
µg/
L
(canola)
Annual
Average
EEC
0.011
µg/
L
(wheat)
0.025
µg/
L
(canola)
33
iii.
Surface
Water
Surface
water
concentrations
from
lindane
use
as
a
seed
treatment
were
previously
estimated
using
the
Generic
Estimated
Environmental
Concentrations
(GENEEC)
model.
The
GENEEC
model
is
no
longer
used
to
estimate
EECs
for
drinking
water,
however.
Therefore,
revised
surface
water
concentrations
were
predicted
with
the
assessment
model,
FIRST.
FIRST
is
based
upon
the
linked
Pesticide
Root
Zone
Model
(PRZM)
which
simulates
pesticides
in
field
run
off
and
Exposure
Analysis
Modeling
System
(EXAMs)
which
simulates
pesticide
fate
and
transport
in
an
aquatic
environment.
FIRST
uses
an
Index
Reservoir
which
is
based
on
Shipman
City
Lake
in
Illinois
(13
acres
in
area,
9
feet
deep,
and
a
watershed
area
of
427
acres).
FIRST
is
designed
to
produce
more
realistic
estimates
of
pesticides
in
surface
water
that
is
used
as
a
source
of
drinking
water.
Table
8
presents
a
summary
of
FIRST
inputs
and
results.
Table
8.
FIRST/
Surface
Water
Input
Parameters
and
Results
for
Lindane
Seed
Treatment.
Parameter
Value
Application
Rate
and
Number
0.
051
lb
ai/
A
x
1
application
(Wheat)
0.
116
lb
ai/
A
x
1
application
(Canola)
Organic
Carbon
Partitioning
Coefficient
942
ml/
g
lowest
of
4
values
(MRID
00164346)
Solubility
7
ppm
Application
Type
Granular/
incorporated
to
1.2
inches
Percent
Cropped
Area
56%
for
Wheat
and
87%
for
Canola
Aerobic
Soil
Half
life
980
days
single
value
(MRID
406225
01)*
Aerobic
Aquatic
Half
life
1960
days
(aerobic
soil
halflife
x
2)
Photolysis
stable
(MRIDs
0016457;
001645545;
447931)
Hydrolysis
stable
(MRID
00161630)
Peak
EEC
0.98
µg/
L
(wheat)
4.16
µg/
L
(canola)
Annual
Average
EEC
0.46
µg/
L
(wheat)
1.95
µg/
L
(canola)
*In
a
336
day
aerobic
soil
metabolism
study,
lindane
degraded
very
slowly,
with
a
registrant
calculated
half
life
of
980
days,
thus
the
"3x"
rule
was
not
applied.
iv.
Drinking
Water
Estimate
Environmental
Concentrations
The
concentrations
presented
in
Table
9
for
drinking
water
EECs
will
be
used
for
the
purposes
of
this
risk
assessment.
The
drinking
water
EECs
for
surface
water
were
based
on
the
FIRST
model
simulations.
Drinking
water
EECs
for
groundwater
were
based
on
SCIGROW
model
simulations.
34
Table
9.
Drinking
Water
EECs
for
Lindane
Drinking
Water
Source
Acute
Chronic
Groundwater
0.025
µ
g/
L
0.
025
µ
g/
L
Surface
Water
4.16
µ
g/
L
1.
95
µ
g/
L
F.
Drinking
Water
Risk
Estimates
Drinking
water
levels
of
comparison
(DWLOCs)
associated
with
acute
and
chronic
exposure
to
lindane
in
drinking
water
have
been
calculated.
These
DWLOCs
are
compared
with
the
EECs
of
lindane
in
ground
water
and
surface
water.
The
DWLOC
is
the
concentration
of
a
chemical
in
drinking
water
that
would
be
acceptable
as
an
upper
limit
in
light
of
total
aggregate
exposure
to
that
chemical
from
food,
water,
and
residential
sources.
The
acute
and
chronic
DWLOC
for
lindane
includes
aggregate
exposure
from
food
and
water
only.
i.
DWLOCs
for
Chronic
Exposure
Chronic
DWLOCs
were
calculated
based
on
the
chronic
dietary
(food)
exposure
estimates
using
lindane
TRR
that
had
been
adjusted
using
feeding
and
metabolism
studies,
along
with
default
body
weights
and
water
consumption
figures.
The
Agency's
default
body
weights
and
water
consumption
values
used
to
calculate
DWLOCs
are
as
follows:
70
kg/
2L
(adult
male),
60
kg/
2L
(adult
female),
and
10
kg/
1L
(infant/
children).
To
calculate
the
chronic
DWLOC,
the
chronic
dietary
food
exposure
was
subtracted
from
the
chronic
PAD
as
shown
in
the
following
equation:
DWLOCchronic
=
[chronic
water
exposure
(mg/
kg/
day)
x
(body
weight)]
[consumption
(L)
x
10
3
mg/
g]
where,
chronic
water
exposure
(mg/
kg/
day)
=
[cPAD
(chronic
food
(mg/
kg/
day)]
The
EECs
for
both
surface
water
and
groundwater
were
less
than
the
chronic
DWLOCs,
indicating
that
chronic
exposure
to
lindane
in
food
and
water
is
less
than
HED's
level
of
concern.
Calculated
chronic
DWLOCs
and
EECs
are
provided
in
Table
10.
Table
10.
Drinking
Water
Levels
of
Comparison
for
Chronic
Dietary
Exposure
Population
Subgroup
Chronic
PAD
(mg/
kg/
day)
Food
Exposure
(mg/
kg/
day)
Max.
Water
Exposure
(mg/
kg/
day)
DWLOCchronic
(ug/
L)
Surface
Water
Annual
Avg
EECs
(ug/
L)
Ground
Water
Annual
Avg
EECs
(ug/
L)
US
Population
0.
0016
0.000054
0.001546
54
1.95
0.025
All
infants
<
1
yr
0.0016
0.000072
0.001528
15
1.95
0.025
Children
(1
6
yrs)
0.
0016
0.000173
0.001427
14
1.95
0.025
Children
(7
12
yrs)
0.0016
0.000096
0.001504
15
1.95
0.025
Females
(13
50
yrs)
0.0016
0.000034
0.001566
47
1.95
0.025
Males
(13
19
yrs)
0.0016
0.000061
0.001539
54
1.95
0.025
Table
10.
Drinking
Water
Levels
of
Comparison
for
Chronic
Dietary
Exposure
Population
Subgroup
Chronic
PAD
(mg/
kg/
day)
Food
Exposure
(mg/
kg/
day)
Max.
Water
Exposure
(mg/
kg/
day)
DWLOCchronic
(ug/
L)
Surface
Water
Annual
Avg
EECs
(ug/
L)
Ground
Water
Annual
Avg
EECs
(ug/
L)
35
Males
20+
0.0016
0.000034
0.001566
55
1.95
0.025
Seniors
55+
0.0016
0.000030
0.00157
55
1.95
0.025
ii.
DWLOCs
for
Acute
Exposure
Acute
DWLOCs
were
calculated
based
on
the
acute
dietary
exposure
estimates
that
were
determined
using
lindane
TRR
adjusted
with
feeding
and
metabolism
studies,
along
with
default
body
weights
and
water
consumption
figures.
The
Agency's
default
body
weights
and
water
consumption
values
used
to
calculate
DWLOCs
are
as
follows:
70
kg/
2
L
(adult
male),
60
kg/
2
L
(adult
female),
and
10
kg/
1
L
(infant/
children).
To
calculate
the
DWLOC,
the
acute
dietary
food
exposure
was
subtracted
from
the
acute
PAD
using
the
equation:
DWLOCacute
=
[acute
water
exposure
(mg/
kg/
day)
x
(body
weight)]
[consumption
(L)
x
10
3
mg/
g]
where,
acute
water
exposure
(mg/
kg/
day)
=
[aPAD
(acute
food
(mg/
kg/
day)]
The
EECs
for
both
surface
water
and
groundwater
were
less
than
the
acute
DWLOCs
for
all
sub
populations
indicating
that
acute
aggregate
exposure
to
lindane
in
food
and
water
is
less
than
HED's
level
of
concern.
Acute
DWLOCs
and
EECs
are
provided
in
Table
11.
Table
11.
Drinking
Water
Levels
of
Comparison
for
Acute
Dietary
Exposure
Population
Subgroup
Acute
PAD
(mg/
kg/
day)
Food
Exposure
(mg/
kg/
day)
Max.
Water
Exposure
(mg/
kg/
day)
DWLOCacute
(ug/
L)
Surface
Water
Peak
EEC
(ug/
L)
Ground
Water
Peak
EEC
(ug/
L)
US
Population
0.
02
0.
0013
0.019
665
4.16
0.025
All
infants
<
1
yr.
0.
02
0.
0033
0.017
170
4.16
0.025
Children
1
6
yrs.
0.02
0.002
0.018
180
4.16
0.025
Children
7
12
yrs.
0.
02
0.
0011
0.019
190
4.16
0.025
Females
13
50
yrs.
0.02
0.0005
0.019
570
4.16
0.025
Males
13
19
yrs
0.
02
0.
0007
0.019
665
4.16
0.025
Males
20+
0.02
0.0005
0.019
665
4.16
0.025
Seniors
55+
0.02
0.0004
0.019
665
4.16
0.025
36
iii.
Non
Dietary
Exposure
Occupational
lindane
exposure
via
dermal
and
inhalation
routes
can
occur
during
handling,
mixing,
loading,
and
applying
activities.
There
are
currently
no
residential
pesticidal
uses
being
supported
for
lindane
and
therefore,
there
is
no
potential
for
residential
exposure
from
pesticidal
uses
of
lindane.
Based
on
toxicological
criteria
and
potential
for
exposure,
HED
has
conducted
separate
dermal
and
inhalation
exposure
assessments
for
a
variety
of
occupational
scenarios.
G.
Occupational
Exposure
and
Risk
Estimates
There
are
potential
exposures
to
mixers,
loaders,
applicators,
or
other
handlers
associated
with
seed
treatment
uses
of
lindane.
Based
on
the
use
patterns
and
potential
exposures
described
above,
5
major
exposure
scenarios
were
identified
as
representative
of
lindane
uses:
(1)
on
farm
seed
treatment
with
dry
formulations
open
transfer
system,
(2)
on
farm
seed
treatment
with
liquid
formulations
closed
transfer
system,
(3)
mixing/
loading
and
applying
liquid
with
commercial
seed
treatment
equipment,
(4)
bagging
and
otherwise
handling
treated
seeds,
(5)
cleaning/
maintaining
seed
treatment
equipment,
and
(6)
loading/
planting
treated
seeds.
To
assess
the
exposures
from
on
farm
treatment
of
the
liquid
formulation
with
a
closed
transfer
system
(scenario
2)
and
commercial
seed
treatment
activities
with
lindane
(scenarios
3,
4a,
4b,
and
5),
the
Agency
considered
all
relevant
data,
including
a
study
which
was
conducted
at
three
seedtreatment
plants
in
Alberta,
Canada,
during
which
lindane
was
one
of
the
active
ingredients
being
monitored
(MRID
44731501).
To
refine
this
assessment,
the
Agency
also
used
surrogate
data
from
a
commercial
seed
treatment
facility
(Helix
study,
MRID
45200002),
from
which
median
unit
dermal
and
inhalation
exposure
measurements
were
available
to
assess
risks
to
various
commercial
seed
treatment
workers,
including
baggers,
sewers,
stackers,
forklift
operators,
and
cleaners.
Because
the
equipment
used
for
on
farm
treatment
with
the
liquid
formulation
has
similar
performance
to
the
equipment
used
in
the
commercial
facility,
exposure
data
from
the
Helix
study
was
also
used
to
assess
workers
treating
seeds
for
this
scenario
(scenario
2).
In
addition,
the
Agency
used
surrogate
exposure
data
(Isophenfos
study,
MRID
42251901)
to
assess
loading
and
planting
treated
seeds
(scenario
6).
Table
12
presents
the
exposure
scenarios,
application
rates,
and
amount
potentially
handled
that
have
been
used
for
the
exposure
calculations.
Exposures
for
handling
treated
seed
before
planting
and
planting
treated
seed
use
parameters
for
wheat
and
canola
as
representative
crops.
Therefore,
the
rates/
seed
types
presented
in
Table
12
are
representative,
rather
than
inclusive,
and
no
attempt
has
been
made
to
assess
a
range
of
application
rates
to
ensure
that
all
use
rate/
exposure
scenarios
are
included.
Table
12:
Exposure
Variables
for
Uses
of
Lindane
Exposure
Scenario
(Scenario
#)
Chemical
Specific
Monitoring
Data
Available?
PHED
Data?
Application
Rates
(lb
ai/
amount
of
seed)
Daily
lb
Seed
Treated/
Handled
Lb
ai
Handled/
day
(1)
on
farm
seed
treatment
with
dry
formulations
open
transfer
system
Yes
Fenske
Study
MRID
#44405802
No
0.023
lb
ai/
bushel
(60
lbs
seed)
for
wheat
0.056
0.
125
lb
ai/
100
lb(
corn)
12000
24000
lbs
seed
(wheat)
1500
2700
lbs
seed
(corn)
5.0
a
9.
3
(wheat)
0.84
3.
4
(corn)
Table
12:
Exposure
Variables
for
Uses
of
Lindane
Exposure
Scenario
(Scenario
#)
Chemical
Specific
Monitoring
Data
Available?
PHED
Data?
Application
Rates
(lb
ai/
amount
of
seed)
Daily
lb
Seed
Treated/
Handled
Lb
ai
Handled/
day
37
(2)
on
farm
seed
treatment
with
liquid
formulations
closed
transfer
system
Yes
Helix
Study
MRID
#45200002
No
0.
043
lb
ai/
100
lb
seed
(wheat)
0.
75
1.
5
lb
ai/
100
lb
seed
(canola)
30000
lbs
seed
b
(wheat)
2000
lbs
seed
(canola)
13
(wheat)
15/
30
(canola)
(3)
mixing/
loading
and
applying
liquid
with
a
commercial
seed
treatment
equipment
Yes
Helix
Study
MRID
#45200002
No
0.
043
lb
ai/
100
lb
seed
(wheat)
0.
75
1.
5
lb
ai/
100
lb
seed
(canola)
176000
lbs
seed
(wheat
and
canola)
76
(wheat)
1320/
2640
(canola)
(4)
handlerfor
commercial
seed
treatment
equipment
(i.
e.
bagging
and
stacking
and
forklift
operator)
Yes
Helix
Study
MRID
#45200002
No
0.
043
lb
ai/
100
lb
seed
(wheat)
0.75
1.5
lb
ai/
100
lb
seed
(canola)
176000
lbs
seed
(wheat
and
canola)
76
(wheat)
1320/
2640
(canola)
(5)
Cleanerfor
commercial
seed
treatment
Yes
Helix
Study
MRID
#45200002
No
Cleaner
daily
inhalation
exposures
measured
in
mg/
kg/
day
were
taken
directly
from
the
HELIX
study.
(6)
Loading
and
Planting
treated
seed
Yes
Isophenphos
Study
MRID
#42251901
Yes
0.
043
lb
ai/
100
lb
seed
(wheat)
0.
75
1.
5
lb
ai/
100
lb
seed
(canola)
30000
lbs
seed
b
(wheat)
2000
lbs
seed
(canola)
13
(wheat)
15/
30
(canola)
a
Data
are
available
from
on
farm
treatment
study;
assumes
120
lbs
wheat
per
acre,
planting
100
200
acres
per
day;
15
lbs
corn/
acre
planting
100180
acres
day
b
Daily
amount
treated
based
on
HEDs
estimates
of
acreage
that
would
be
reasonably
expected
to
be
planted
in
a
day
for
commercially
treated
seed
or
seed
treated
with
an
on
farm
closed
system.
Assumes
120
lbs
wheat/
acre,
8
lbs
canola/
acre,
planting
an
average
of
250
acres/
day.
i.
Commercial
Seed
Treatment
HED
has
revised
its
assessment
of
occupational
exposure
for
commercial
seed
treatment.
The
previous
assessment
was
based
on
a
commercial
seed
treatment
study
(MRID
44731501)
which
was
of
a
lesser
quality
and
probably
did
not
address
changes
in
the
technology
that
have
occurred
since
the
study
was
conducted
.
The
revised
assessment
is
based
on
a
study
measuring
exposures
of
workers
treating
canola
seed
with
HELIX
289S
(a
mixture
of
thimethozam,
difenconazole,
metalaxyl,
and
fludioxonil).
The
study
was
reviewed
jointly
by
EPA
and
PMRA
(MRID
45200002).
The
HELIX
289S
Study
is
comprehensive
occupational
exposure
study
designed
and
conducted
to
quantify
potential
exposure
to
thiamethoxam,
formulated
as
a
flowable
liquid,
during
commercial
treatment
of
canola
seed.
Lindane
end
use
products
for
canola
use
are
liquids
(flowable
formulation).
Lindane
products
for
grower
use
on
small
grains,
corn,
and
sorghum
are
dust
and
wettable
powders
and
liquids.
In
the
absence
of
more
formulation
specific
data,
HED
believes
the
HELIX
Study
provides
the
best
data
available
for
assessing
exposure/
risk
from
commercial
seed
treatment
with
lindane.
HED
has
reevaluated
the
estimates
of
exposure
and
risk
from
treatment
of
wheat
and
canola
seed
with
lindane
using
unit
dermal
and
inhalation
exposures
provided
in
the
HELIX
289FS
Study.
A
detailed
description
of
the
study
and
the
calculations
for
exposure
assessment
are
provided
in
an
April
23,
2002
memorandum
from
D.
Jaquith
(D282419).
ii.
On
Farm
Seed
Treatment
and
Planting
of
Treated
Seed
Based
on
seed
treatment
surveys
and
conversations
with
experts
in
the
field,
the
vast
majority
(98%)
of
lindane
seed
treatments
are
incorporated
into
the
seed
on
farm;
very
little
is
38
incorporated
into
the
seed
by
seed
processors.
Corn
and
oats
are
exclusively
treated
on
farm
(BEAD's
Impact
Analysis
of
the
Seed
Treatment
Uses
of
Lindane
on
Wheat,
Barley,
Oats,
Rye,
Corn,
Sorghum,
andCanola,
D.
Brassard,
2/
5/
00).
HED'sevaluationofonfarmseedtreatment
in
an
open
system
was
based
on
a
study
of
worker
exposure
to
lindane
during
manual
treatment
of
winter
wheat
(Fenske,
MRID
44405802;
D283397).
HED
also
evaluated
the
exposures
of
workers
using
on
farm
seed
treatment
transfer
systems
for
liquid
formulations
which
provide
a
more
enclosed
environment.
For
the
closed
transfer
system
worker
exposure
analysis,
HED
used
median
unit
dermal
and
inhalation
exposures
provided
in
the
HELIX
289FS
commercial
seed
treatment
study
to
estimate
exposure
and
risk
from
lindane
treatment
of
wheat
and
canola
seed.
HED
has
also
reevaluated
exposures
from
the
loading
and
planting
of
seed
treated
with
lindane.
These
revisions
are
based
on
data
provided
in
a
study
measuring
exposures
of
workers
to
isophenphos
during
planting
of
oftanol
treated
canola
seed
(MRID
No.
42251901).
A
detailed
description
of
the
study
and
the
calculations
for
exposure
assessment
are
provided
in
exposure
assessment
memoranda
from
D.
Jaquith
(D282418,
D283397).
The
revised
assessment
also
uses
a
higher
seeding
rate
of
8
lb/
seed/
acre.
The
previous
assessment
assumed
a
seeding
rate
of
4
lb/
seed/
acre.
iii.
Occupational
Exposure
and
Risk
Occupational
exposure
scenarios
assessed
are
summarized
in
Table
13.
The
daily
exposures,
as
well
as
the
resulting
short
and
intermediate
term
MOEs
are
presented
in
Table
14.
Short
and
intermediate
(if
applicable)
term
MOEs
were
calculated
for
dermal
and
inhalation
exposure
routes
for
a
total
of
five
worker
exposure
scenarios.
The
analysis
indicates
MOEs
of
concern
(MOE<
100)
for
the
following
exposure
scenarios/
pathways:
dermal
exposure
from
on
farm
seed
treatment;
inhalation
exposure
from
commercial
treatment
(mixing/
loading/
application)
of
canola
seed
at
both
high
and
low
end
rates
of
1.
5
and
0.
75
lb/
100
lb
seed;
and
inhalation
exposure
from
commercial
handling
of
canola
treated
at
the
high
end
application
rate
of
1.
5
lb/
100
lb
seed.
All
other
exposure
scenarios
result
in
MOEs
that
are
not
of
concern
for
either
dermal
or
inhalation
exposure
pathways.
Dermal
MOEs
for
all
scenarios
range
between
9
and
190000.
Inhalation
MOEs
range
from
30
to
16000.
MOEs
are
not
of
concern
for
the
on
farm
worker
using
a
closed
system
and
wearing
protective
clothing
similar
to
that
of
commercial
seed
treatment
plant
workers.
However,
it
must
be
noted
that
the
exposure/
risk
assessments
presented
in
Table
13
for
the
on
farm
closed
transfer
system
scenario
are
valid
only
if
the
type
of
equipment
and
protective
clothing
used
in
the
surrogate
HELIX
study
are
employed.
Therefore,
this
closed
system
exposure/
risk
assessment
can
be
used
for
regulatory
purposes
only
if
the
personal
protective
measures
assumed
in
the
analysis
are
required
on
the
label.
Table
13.
Exposure
Scenario
Descriptions
for
the
Use
of
Lindane.
Exposure
Scenario
Data
Source
Standard
Assumptions
a
Comments
On
farm
seed
treatment
with
dry
formulation
open
transfer
system
(1)
Rhone
Poulenc
Data
Fenske
Study
MRID
#
444058
02
Assumes
enough
seed
treated
and
planted
for
100
Acres
per
day
low
end,
180/
200
Acres
per
day
high
end
All
data
were
for
gloved
hands;
(see
study,
Appendix
A,
D283397)
Table
13.
Exposure
Scenario
Descriptions
for
the
Use
of
Lindane.
Exposure
Scenario
Data
Source
Standard
Assumptions
a
Comments
39
On
farm
seed
treatment
with
liquid
formulation
closed
transfer
system
(2)
HELIX
Study
Data
MRID
#
45200002
Assumes
250
acres
are
planted
per
day
at
120
lbs
of
wheat;
8
lbs
of
canola
seed
per
acre
See
study
review,
based
on
Imazilil
Assessment
and
BEAD
data
Mixing/
loading/
application
of
liquid
formulation
for
commercial
seed
treatment
(3)
HELIX
Study
Data
MRID
#
45200002
Assumes
throughput
of
seed
for
both
wheat
and
canola
is
176000
lbs
per
8
hour
day
See
study
review;
based
on
amounts
of
seed
from
study
data
Seed
Handler
for
commercial
seed
treatment
(4)
HELIX
Study
Data
MRID
#
45200002
Assumes
throughput
of
seed
for
both
wheat
and
canola
is
176000
lbs
per
8
hour
day
See
study
review;
based
on
amounts
of
seed
from
study
data
Cleaner
for
commercial
seed
treatment
(5)
HELIX
Study
Data
MRID
#
45200002
Based
on
practices
used
in
the
HELIX
Study
See
study
review;
based
on
amounts
of
seed
from
study
data
Loading
and
Planting
treated
seed
(6)
Isophenphos
Study
Data
MRID
#42251901
Assumes
250
acres
are
planted
per
day
at
120
lbs
of
wheat;
8
lbs
of
canola
seed
per
acre
See
study
review,
based
on
Imazilil
Assessment
and
BEAD
data
a
All
Standard
Assumptions
are
based
on
an
8
hour
work
day
as
estimated
by
HED.
Table
14:
Daily
Exposures,
Short
and
Intermediate
MOEs
of
Workers
to
Lindane
During
Seed
Treatment
and
Planting
of
Treated
Seed.
Exposure
Scenario
(Scenario
#)
Crop
Application
Rates
(
lb
ai/
100
lbs
seed
or
Lb/
A)
Amount
Handled
per
Day
(lbs
a.
i.)
Unit
Exposure
(mg/
lb
ai)
a
Daily
Exposure
(mg/
kg/
day)
Short
Term
&
Intermediate
Term
b
MOEs
Dermal
Inhalation
Dermal
c
Inhalation
e
Dermal
d
Inhalation
f
On
farm
seed
treatment
with
dry
formulation
open
transfer
system
(1)
wheat
0.043
5
(100A
planted)
9.4
0.
0016
0.70
0.0001
17
1100
0.043
10
(200
A
planted)
9.4
0.
0016
1.39
0.0002
9
550
corn
0.056
low
end
0.84(
100
A
planted)
9.4
0.
0016
0.11
0.00002
92
6500
1.5
(180
A
planted)
9.4
0.
0016
0.20
0.00003
60
3700
0.125
high
end
1.9
(100
A
planted)
9.4
0.
0016
0.25
0.00004
48
3000
3.4
(180
A
planted)
9.4
0.
0016
0.45
0.00007
26
1700
On
farm
seed
treatment
with
liquid
formulation
closed
transfer
system
(2)
wheat
0.043
13
0.00083
0.00012
0.0002
0.000022
67000
5900
canola
1.5
high
end
30
0.00083
0.00012
0.0004
0.00005
29000
2500
0.75
low
end
15
0.00083
0.00012
0.0002
0.000026
57000
5000
Mixing/
loading/
application
of
liquid
formulation
for
commercial
seed
treatment
Treater
Closed
Transfer
chemical
resistant
coveralls
over
long
sleeved
shirt,
longpants,
chemical
resistant
gloves(
3)
wheat
0.043
76
0.00083
0.00012
0.0010
0.00013
11000
1000
canola
1.5
high
end
2640
0.00083
0.00012
0.036
0.0045
330
30
0.75
low
end
1320
0.00083
0.00012
0.018
0.0023
660
60
Seed
Handler
for
commercial
seed
treatment
Bagger/
Sewer/
Stacker
chemical
resistant
coveralls
over
long
sleeved
shirt,
long
pants,
chemical
resistant
gloves
(4a)
wheat
0.043
76
0.00026
0.00006
0.00033
6.5E
05
37000
2000
canola
1.5
high
end
2640
0.00026
0.00006
0.011
0.0023
1000
60
0.75
low
end
1320
0.00026
0.00006
0.0057
0.0011
2100
120
Table
14:
Daily
Exposures,
Short
and
Intermediate
MOEs
of
Workers
to
Lindane
During
Seed
Treatment
and
Planting
of
Treated
Seed.
Exposure
Scenario
(Scenario
#)
Crop
Application
Rates
(
lb
ai/
100
lbs
seed
or
Lb/
A)
Amount
Handled
per
Day
(lbs
a.
i.)
Unit
Exposure
(mg/
lb
ai)
a
Daily
Exposure
(mg/
kg/
day)
Short
Term
&
Intermediate
Term
b
MOEs
Dermal
Inhalation
Dermal
c
Inhalation
e
Dermal
d
Inhalation
f
40
Seed
Handler
for
commercial
seed
treatment
Forklift
Operator
cotton/
polyester
coveralls
over
long
sleeved
shirt,
long
pants,
chemical
resistant
gloves
(4b)
wheat
0.043
76
0.00008
8E
06
0.
00010
8.3E
06
119000
16000
canola
1.5
high
end
2640
0.00008
8E
06
0.
0035
0.00029
3400
450
0.75
low
end
1320
0.00008
8E
06
0.
0018
0.00015
6800
900
Cleaner*
chemical
resistant
coveralls
over
long
sleeved
shirt,
long
pants,
chemical
resistant
gloves
(5)
wheat
NA
NA
NA
NA
0.0067
0.0012
1800
110
canola
NA
NA
NA
NA
0.
0067
0.0012
1800
110
Loading
and
Planting
Treated
Seed
(6)
wheat
0.043
13
0.06
0.0006
0.013
00011
920
1200
canola
1.5
high
end
30
0.06
0.0006
0.03
0.00026
400
500
0.75
low
end
15
0.06
0.0006
0.015
0.00013
800
1000
a
Median
unit
dermal
and
inhalation
unit
exposures
b
Intermediate
term
MOEs
are
not
applicable
for
Scenarios
(1)
On
Farm
Seed
Treatment
and
(5)
Planting
Treated
Seed.
c
Daily
Dermal
Exposure
(mg/
kg/
day)
=
unit
exposure
(mg/
lb
ai)
x
amount
handled
per
day
(lbs
a.
i.)
/
bw
(60
kg).
d
Dermal
MOE
=
Oral
NOAEL
(1.
2
mg/
kg)
/
[daily
exposure
(mg/
kg/
day)
x
dermal
absorption
factor
(10%)].
e
Daily
Inhalation
Exposure
(mg/
kg/
day)
=
inhalation
unit
exposure
(mg/
lb
ai)
x
amount
handled
per
day
(lbs
a.
i.)
/
body
weight
(70
kg).
*Cleaner
daily
inhalation
exposures,
measured
in
mg/
kg/
day,
were
taken
directly
from
the
HELIX
study.
f
Inhalation
MOE
=
NOAEL
(0.
13
mg/
kg/
day)
/
daily
exposure
(mg/
kg/
day).
V.
Aggregate
and
Cumulative
Exposure
and
Risk
Characterization
The
Food
Quality
Protection
Act
amendments
to
the
Federal
Food,
Drug,
and
Cosmetic
Act
(FFDCA,
Section
408(
b)(
2)(
A)(
ii))
require
that
for
establishing
a
pesticide
tolerance
"that
there
is
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
pesticide
chemical
residue,
including
all
anticipated
dietary
exposures
and
other
exposures
for
which
there
are
reliable
information."
Aggregate
exposure
is
the
total
exposure
to
a
single
chemical
(or
its
residues)
that
may
occur
from
dietary
(i.
e.,
food,
and
drinking
water),
residential
and
other
non
occupational
sources,
and
from
all
known
or
plausible
exposure
routes
(oral,
dermal
and
inhalation).
Aggregate
risk
assessments
are
typically
conducted
for
acute
(1
day),
short
term
(1
7
days),
intermediate
term
(7
days
to
several
months),
and
chronic
(several
months
to
lifetime)
exposure.
41
A.
Acute
Aggregate
Risk
The
acute
aggregate
risk
estimate
to
lindane
addresses
exposures
from
food
and
drinking
water
only
since
there
are
no
residential
pesticide
uses
remaining.
The
lindane
acute
dietary
risk
estimates,
including
all
sources
of
residues
of
lindane,
range
from
2%
to
17%
of
the
aPAD
at
the
99.9
th
percentile
of
the
population,
with
infants
(<
1yr)
being
the
highest
exposed
population
subgroup.
Thus,
the
acute
dietary
(food)
risk
estimate
associated
with
lindane
exposure
is
below
the
Agency's
level
of
concern.
Based
on
SCI
GROW
model
simulations,
the
acute
estimated
concentration
(EEC)
of
lindane
in
groundwater
from
seed
treatment
uses
is
0.025
µg/
L.
The
acute
surface
water
EECs
resulting
from
the
use
of
lindane
are
4.
16
µg/
L
based
on
FIRST
modeling
results.
The
EECs
from
the
use
of
lindane
are
less
than
the
DWLOCs
for
all
populations,
indicating
that
acute
food
and
drinking
water
exposures
do
not
exceed
the
Agency's
level
of
concern.
It
should
be
noted
that
neither
the
model
nor
the
monitoring
data
reflect
concentrations
after
dilution
(from
source
to
treatment
to
tap)
or
drinking
water
treatment.
HED
concludes
that
acute
aggregate
lindane
exposure
in
food
and
water
from
the
use
of
lindane
does
not
exceed
the
Agency's
level
of
concern.
B.
Short
and
Intermediate
Term
Aggregate
Risk
The
short
and
intermediate
term
aggregate
risk
estimate
includes
chronic
dietary
(food
and
water)
from
lindane
uses,
and
intermediate
term
non
occupational
exposures
(i.
e.,
residential/
recreational
uses).
There
are
no
residential/
recreational
seed
treatment
uses
with
a
short
or
intermediate
term
exposure
scenario.
Therefore,
a
short
and
intermediate
term
aggregate
risk
estimate
were
not
evaluated.
C.
Chronic
Aggregate
Risk
Chronic
aggregate
risk
estimates
do
not
exceed
HED's
level
of
concern.
The
aggregate
chronic
dietary
risk
estimates
include
exposure
to
lindane
residues
in
food
and
water
only
since
no
chronic
residential
pesticide
use
scenarios
were
identified.
The
resulting
risk
estimates
are
3
%
of
the
chronic
PAD
(%
cPAD)
for
the
U.
S.
Population
and
11
%
of
the
cPAD
for
Children
1
6
years
of
age
(the
most
highly
exposed
population
subgroup).
The
remaining
population
subgroups
were
between
2%
and
6
%
of
the
cPAD
when
the
feeding
studies
were
adjusted
using
the
metabolism
studies.
Using
the
FIRST
model,
the
estimated
average
concentration
of
lindane
in
surface
water
resulting
from
seed
treatment
uses
is
1.95
ppb.
The
chronic
EEC
for
groundwater
based
on
the
SCI
GROW
model
0.025.
Both
surface
and
groundwater
EECs
are
less
than
HED's
respective
drinking
water
level
of
comparison
for
exposure
to
lindane.
Mean
and
median
concentrations
from
monitoring
data
are
also
below
HED's
calculated
DWLOCs.
Based
on
the
42
available
information,
HED
concludes
with
reasonable
certainty
that
no
harm
to
any
population
will
result
from
chronic
aggregate
exposure
to
lindane.
D.
Cumulative
Exposure
and
Risk
The
Food
Quality
Protection
Act
(1996)
stipulates
that
when
determining
the
safety
of
a
pesticide
chemical,
EPA
shall
base
its
assessment
of
the
risk
posed
by
the
chemical
on,
among
other
things,
available
information
concerning
the
cumulative
effects
to
human
health
that
may
result
from
dietary,
residential,
or
other
non
occupational
exposure
to
other
substances
that
have
a
common
mechanism
of
toxicity.
The
reason
for
consideration
of
other
substances
is
due
to
the
possibility
that
low
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.
A
person
exposed
to
a
pesticide
at
a
level
that
is
considered
safe
may
in
fact
experience
harm
if
that
person
is
also
exposed
to
other
substances
that
cause
a
common
toxic
effect
by
a
mechanism
common
with
that
of
the
subject
pesticide,
even
if
the
individual
exposure
levels
to
the
other
substances
are
also
considered
safe.
HED
did
not
perform
a
cumulative
risk
assessment
as
part
of
this
reregistration
review
for
lindane
because
HED
has
not
yet
initiated
a
review
to
determine
if
there
are
any
other
chemical
substances
that
have
a
mechanism
of
toxicity
common
with
that
of
lindane.
For
purposes
of
this
reregistration
decision
,
EPA
has
assumed
that
lindane
does
not
have
a
common
mechanism
of
toxicity
with
other
substances.
On
this
basis,
the
registrant
must
submit,
upon
EPA's
request
and
according
to
a
schedule
determined
by
the
Agency,
such
information
as
the
Agency
directs
to
be
submitted
in
order
to
evaluate
issues
related
to
whether
lindane
shares
a
common
mechanism
of
toxicity
with
any
other
substance
and,
if
so,
whether
any
tolerances
for
lindane
need
to
be
modified
or
revoked.
If
HED
identifies
other
substances
that
share
a
common
mechanism
of
toxicity
with
lindane,
HED
will
perform
aggregate
exposure
assessments
on
each
chemical,
and
will
begin
to
conduct
a
cumulative
risk
assessment.
HED
has
recently
developed
a
framework
that
it
proposes
to
use
for
conducting
cumulative
risk
assessments
on
substances
that
have
a
common
mechanism
of
toxicity.
This
guidance
was
issued
for
public
comment
on
January
16,
2002
(67
FR
2210
2214)
and
is
available
fromthe
OPPWebsite
at:
http://
www.
epa.
gov/
pesticides/
trac/
science/
cumulative_
guidance.
pdf
In
the
guidance,
it
is
stated
that
a
cumulative
risk
assessment
of
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
will
not
be
conducted
until
an
aggregate
exposure
assessment
of
each
substance
has
been
completed.
Before
undertaking
a
cumulative
risk
assessment,
HED
will
follow
procedures
for
identifying
chemicals
that
have
a
common
mechanism
of
toxicity
as
set
forth
in
the
"Guidance
for
Identifying
Pesticide
Chemicals
and
Other
Substances
that
Have
a
Common
Mechanism
of
Toxicity"
(64
FR
5795
5796,
February
5,
1999).
43
VI.
Risk
Characterization
The
lindane
risk
assessment
contains
strengths,
weaknesses,
and
uncertainties
based
on
the
existing
toxicological
and
exposure
data,
modeling
methodologies,
data
gaps,
and
gaps
in
scientific
knowledge.
This
assessment
uses
standard
assumptions
regarding
human
body
weight,
work
life,
and
other
exposure
parameters;
and
interspecies
extrapolation
to
estimate
risks.
Additional
assumptions
were
made
regarding
route
to
route
extrapolation.
Strengths
and
uncertainties
of
the
assessment
are
described
below.
The
OPP/
Cancer
Assessment
Review
Committee
(CARC)
has
completed
the
review
of
newly
submitted
carcinogenicity
study
in
CD
1
mice
along
with
other
data.
In
accordance
with
the
EPA
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(July,
1999),
the
CARC
has
classified
lindane
into
the
category
"Suggestive
evidence
of
carcinogenicity,
but
not
sufficient
to
assess
human
carcinogenic
potential"
based
on
an
increased
incidence
of
benign
lung
tumors
in
female
mice
only.
The
Committee,
therefore,
recommended
that
the
quantification
of
human
cancer
risk
is
not
required.
Lindane
is
a
neurotoxicant.
In
acute,
subchronic
and
developmental
neurotoxicity
studies,
it
was
found
to
cause
neurotoxic
effects
including
tremors,
convulsions,
decreased
motor
activity,
increased
forelimb
grip
strength,
hypersensitivity
to
touch,
hunched
posture
and
decreased
motor
activity
habituation.
There
also
appears
to
be
a
greater
susceptibility
to
exposure
by
offspring
compared
to
parental
animals
in
the
developmental
neurotoxicity
study.
Lindane
has
also
been
implicated
as
a
possible
endocrine
disruptor
in
birds,
mammals
and
possibly
fish.
Further
studies
to
ascertain
the
validity
of
such
evidence
is
necessary
to
make
informed
risk
assessment
decisions.
Lindane
is
distributed
to
all
organs
at
measurable
concentrations
within
a
few
hours
after
oral
administration.
The
highest
concentrations
are
found
in
adipose
tissue.
The
metabolism
of
lindane
is
initiated
through
one
of
several
pathways:
Dehydrogenation
leading
to
gamma
HCH,
dehydrochlorination
leading
to
formation
of
gamma
hexchlorohexene
or
hydroxylation
leading
to
formation
of
hexachlorocyclohexanol.
Further
metabolism
leads
to
a
large
number
of
metabolites.
Lindane
is
converted
by
enzymatic
reactions,
mainly
in
the
liver.
Lindane
appears
to
affect
the
liver
and
kidney
in
male
rats
when
administered
through
the
oral,
dermal
or
inhalation
routes
of
exposure.
Kidney
lesions
in
males
indicative
of
alpha
2µ
globulin
accumulation
were
observed
in
animals
treated
with
10
ppm,
but
are
not
considered
relevant
to
human
health
risk
assessment
The
liver
effects
include:
incidence
of
periacinar
hepatocytic
hypertrophy
which
was
significantly
(p
0.01)
increased
in
male
and
female
rats
dosed
at
100
ppm
(4.
81
and
6.00
mg/
kg/
day,
respectively).
In
addition,
increased
liver
and
spleen
weights,
and
decreased
platelets
were
also
noted.
44
Lindane
is
not
considered
teratogenic
when
administered
orally
or
subcutaneously.
Developmental
NOAELs
were
found
to
be
at
levels
equal
to
or
greater
than
maternal
NOAELs,
except
in
the
developmental
neurotoxicity
study.
The
developmental
neurotoxicity
LOAEL
was
5.6
mg/
kg/
day
(NOAEL
was
1.
2
mg/
kg/
day)
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation
compared
to
a
maternal
toxicity
LOAEL
of
13.7
mg/
kg/
day
(NOAEL
is
5.6
mg/
kg/
day)
based
on
decreased
body
weight
gains,
decreased
food
consumption,
and
increased
reactivity
to
handling.
The
data
base
for
reproductive
toxicity
is
considered
complete.
Both
parental
and
offspring
LOAELs
are
13
mg/
kg;
however
there
is
a
qualitative
difference
in
the
severity
of
effects.
In
the
parental
animals,
toxicity
was
seen
in
the
form
of
reduction
in
body
weight
gain
during
gestation
while
offspring
toxicity
was
correlated
with
decreases
in
pup
viability
and
pup
body
weight
in
the
F1
and
F2
generations
as
well
as
delayed
maturation
in
the
F2
generation.
Evidence
for
quantitative
increase
in
susceptibility
could
not
be
ascertained
due
to
the
wide
spread
in
the
doses
tested.
In
a
mammalian
cell
gene
mutation
assay
and
an
in
vivo
sister
chromatid
exchange
assay,
no
mutagenic
response
was
detected.
These
studies
were
classified
as
unacceptable.
The
open
literature
suggests,
however,
that
technical
grade
HCH
(hexachlorohexane;
6.
5%
HCH)
may
induce
some
mutagenic
activity
as
evidenced
in
a
dominant
lethal
mutation
assay
and
sister
chromatid
exchanges.
It
has
been
noted,
however,
by
the
IPCS
that
lindane
does
not
appear
to
have
a
mutagenic
potential.
There
are
no
adequate
nature
of
the
residue
studies
for
plants
from
seed
treatment
application.
A
new
metabolism
study
is
required
for
cereal
grains;
however,
a
seed
treatment
metabolism
study
(which
was
classified
as
inadequate)
was
reviewed
by
the
Agency
and
used
in
the
determination
of
the
TRR
for
use
in
the
dietary
exposure
analysis.
Additional
residue
data
would
be
required
if
the
HED
MARC
determines
residues
of
concern
include
metabolites
of
lindane
in
addition
to
lindane
per
se.
The
lindane
residue
values
were
derived
using
a
ratio
of
total
radioactive
residue
divided
by
the
amount
of
lindane
present
in
the
metabolism
studies.
This
would
be
worstcase
estimatesince
we
areassuming
thatallofthe
TRRwould
be
residues
of
concern.
The
dietary
exposure
analyses
using
the
total
radioactive
residues
is
a
Tier
3
assessment
since
percent
crop
treated
was
used
in
the
analyses.
The
dietary
exposure
analyses
that
were
based
on
the
adjustment
of
the
lindane
residues
in
the
feeding
studies
is
a
Tier
3
assessment.
Percent
market
share
was
available
for
all
crops
included
in
the
analyses.
Since
lindane
is
registered
for
seed
treatments
only,
there
is
no
difference
in
the
percent
crop
treated
values
between
crops
grown
for
the
fresh
market
and
those
grown
for
processing.
A
processing
study
was
available
for
canola
only;
the
default
DEEM™
processing
factors
were
used
for
all
other
foods.
45
No
acute
or
chronic
residential
use
scenarios
were
identified
for
lindane;
therefore,
aggregate
risk
estimates
address
exposures
from
food
and
drinking
water
only.
The
lindane
acute
dietary
risk
estimates,
including
all
sources
of
residues
of
lindane,
range
from
7%
to
17%
of
the
aPAD
at
the
99.9
th
percentile
of
the
population,
with
infants
(<
1yr)
being
the
highest
exposed
population
subgroup.
Thus,
the
acute
dietary
(food)
risk
estimate
associated
with
lindane
exposure
is
below
the
Agency's
level
of
concern.
The
aggregate
chronic
dietary
risk
estimates
include
exposure
to
lindane
residues
in
food
and
water.
The
resulting
risk
estimates
are
3
%
of
the
chronic
PAD
(%
cPAD)
for
the
U.
S.
Population
and
11
%
of
the
cPAD
for
Children
1
6
years
of
age
(the
most
highly
exposed
population
subgroup).
The
remaining
population
subgroups
were
<6
%
of
the
cPAD
when
the
total
radioactive
residue
is
adjusted
using
the
metabolism
studies.
Chronic
aggregate
risk
estimates,
therefore,
do
not
exceed
HED's
level
of
concern.
Exposure
estimates
for
a
number
of
occupational
scenarios
were
derived
from
limited
data
from
the
submitted
studies,
scientific
literature,
and
knowledge
of
cultural
practices,
in
combination
with
models
and
literature
studies.
No
residential
exposure
assessment
was
conducted
by
the
Agency
since
pesticide
uses
have
been
limited
to
seed
treatment
only.
The
Agency
considers
the
occupational
exposure
estimates
to
be
the
best
available
with
current
methodologies.
The
analysis
indicates
MOEs
of
concern
(MOE<
100)
for
the
following
exposure
scenarios/
pathways:
dermal
exposure
from
on
farm
seed
treatment;
inhalation
exposure
from
commercial
treatment
(mixing/
loading/
application)
of
canola
seed
at
both
high
and
low
end
rates
of
1.
5
and
0.
75
lb/
100
lb
seed;
and
inhalation
exposure
from
commercial
handling
of
canola
treated
at
the
high
end
application
rate
of
1.
5
lb/
100
lb
seed.
All
other
exposure
scenarios
result
in
MOEs
that
are
not
of
concern
for
either
dermal
or
inhalation
exposure
pathways.
Volatilization
appears
to
be
an
important
route
of
its
dissipation
under
the
high
temperature
conditions
of
tropical
regions.
The
presence
of
lindane
in
the
environment,
due
to
previous
widespread
agricultural
use,
is
well
documented
in
U.
S.
data
bases.
For
example,
In
the
U.
S.
EPA
STORET
data
base,
720
detections
in
ground
water
were
reported
between
the
years
1968
and
1995,
in
nearly
all
regions
of
the
country,
with
especially
high
numbers
of
detections
in
the
South
and
West.
For
these
720
detections,
the
median
and
mean
concentrations
were
0.01
and
11
µg/
L,
respectively.
For
surface
waters,
8775
detections
were
reported
with
median
and
mean
concentrations
of
0.005
and
0.
18
µg/
L.
STORET
Detections
were
reported
in
nearly
all
regions
of
the
conterminous
U.
S.
In
the
USGS
NAWQA
study,
lindane
was
detected
in
2.58%
of
surface
water
samples
(0.
67%
at
levels
greater
than
0.05
µ
g/
L,
maximum
concentration
reported
was
0.13
µ
g/
L).
For
groundwater,
USGS
NAWQA
reported
a
detection
frequency
of
0.
1
%
(0.07%
at
levels
greater
than
0.01
µ
g/
L,
maximum
concentration
reported
was
0.
032
µ
g/
L).
HCH
and
Lindane
have
been
found
in
the
tissues
and
fat
of
humans
living
in
the
Arctic.
It
appears
that
lindane
is
transported
from
regions
where
it
is
used
to
the
Arctic
and
has
been
found
at
detectable
levels
in
the
food
supply
of
the
indigenous
populations
of
Alaska
and
the
Northwest
Territories.
Detectable
levels
of
lindane
along
with
other
isomers
of
HCH
have
been
documented
in
fish,
elk,
caribou
and
other
aquatic
and
wildlife.
It
persists
in
the
air,
water,
and
46
soil
and
continues
to
show
patterns
of
long
range
atmospheric
movement
into
areas
where
it
has
been
banned
or
never
been
used.
The
continued
worldwide
use
of
lindane
may
pose
an
environmental,
as
well
as
a
human
toxicologic
risk
to
the
indigenous
peoples
of
the
Arctic.
The
Indigenous
Peoples
of
the
Arctic
region
of
the
U.
S.
(Alaska)
rely
heavily
on
subsistence
diets
as
their
food
source.
Thus,
it
is
appropriate
for
the
Agency
to
perform
a
supplementary
dietary
risk
and
exposure
assessment
to
assess
the
risk
to
the
Indigenous
People
from
worldwide
use
and
manufacture
of
lindane.
HED
performed
a
revised
supplementary
chronic
dietary
risk
and
exposure
assessment
to
assess
the
risk
to
Indigenous
People
from
worldwide
use
and
manufacture
of
lindane
(T.
Morton,
D222455,
4/
17/
02).
Based
on
this
revised
exposure
estimate,
the
chronic
dietary
risk
to
male
and
female
adult
Indigenous
People
is
below
HED's
level
of
concern.
Revised
estimate
of
risks
to
a
10
kg
child
results
in
an
estimated
chronic
dietary
risk
to
an
Indigenous
child
(1
6
years)
of
0.0002
0.
0022
mg/
kg/
day
(13
to
138%
cPAD).
Revised
estimate
of
chronic
dietary
risk
to
a
7
12
year
old
indigenous
child
(29
kg
body
weight)
is
0.
00007
0.
0008
mg/
kg/
day
or
4
48%
of
the
cPAD
which
is
below
HED's
level
of
concern.
It
should
be
noted
that
factors
such
as
bioaccumulation
of
lindane
and
the
cumulative
effects
of
combinations
of
chemicals
which
act
through
a
common
mode
of
action
have
not
been
incorporated
into
this
assessment.
As
the
Agency
develops
its
cumulative
risk
assessment
policies,
if
lindane
is
found
to
share
a
common
mode
of
action
with
other
chemicals,
a
more
comprehensive
evaluation
of
the
contribution
to
public
risk
will
be
initiated.
This
risk
assessment
does
not
at
this
time
include
an
assessment
of
risks
from
exposure
to
lindane
from
uses
other
than
seed
treatment
(e.
g.,
use
of
lindane
to
treat
head
lice
or
scabies).
VII.
Data
Needs
Most
of
the
Reregistration
data
requirements
for
Lindane
have
been
fulfilled.
The
few
remaining
data
requirements
are
described
below.
A.
Toxicology
Data
Requirements
870.3700b
Prenatal
developmental
in
rabbit
870.5300
Gene
Mutation
Mammalian
Cell
870.5450
Dominant
Lethal
Assay
870.5915
In
Vivo
Sister
Chromatid
Exchange
Although
the
prenatal
developmental
study
in
rabbits
was
found
unacceptable,
a
new
study
is
not
being
required
at
this
time.
The
rationale
for
this
decision
is
contained
in
the
body
of
this
document.
No
further
genetic
toxicity
testing
are
required
at
this
time.
The
mutagenic
potential
of
lindane
will
be
reevaluated
in
conjunction
with
the
carcinogenicity
review
and
a
determination
as
to
the
need
for
further
studies
will
occur
at
that
time.
47
B.
Product
and
Residue
Chemistry
Data
Requirements
Product
Chemistry
All
pertinent
product
chemistry
data
are
satisfied
for
the
Kanoria
99.5%
T/
TGAIs
except
additional
data
are
required
concerning
UV/
visible
absorption
(OPPTS
830.7050).
Pertinent
product
chemistry
data
remain
outstanding
for
the
Inquinosa
99.5%
T/
TGAI
concerning
product
identity,
starting
materials
and
production
process,
preliminary
analysis,
certified
limits,
oxidation/
reduction,
explodability,
storage
stability,
corrosion
characteristics,
and
UV/
visible
absorption
(OPPTS
830.1550,
1600,
1620,
1700,
1750,
6314,
6316,
6317,
6320,
and
7050).
These
data
have
been
submitted
and
are
currently
under
review
by
HED
(T.
Morton,
D276302).
Technical
products
registered
to
Kanoria
Chemicals
&
Industries
were
suspended
effective
12/
5/
00
for
failure
to
comply
with
a
cost
sharing
agreement
with
Inquinosa.
Therefore,
all
technicals
registered
which
are
repackages
of
the
Kanoria
products
would
be
required
to
change
suppliers.
The
Kanoria
products
are
shown
in
data
summary
tables
which
are
attached
to
the
Revised
Residue
Chemistry
Chapter
(T.
Morton,
12/
11/
01,
D279259)
for
informational
purposes
only.
The
Prentiss,
Drexel,
and
Amvac
99.
5%
technicals
are
repackaged
from
EPA
registered
products,
and
all
data
requirements
will
be
satisfied
by
data
for
the
technical
source
products.
Provided
that
the
registrants
submit
the
data
required
in
the
data
summary
tables
for
the
lindane
T/
TGAIs
in
the
Product
and
Residue
Chemistry
Chapters
(T.
Morton,
279259)
and
either
certify
that
the
suppliers
of
beginning
materials
and
the
manufacturing
processes
have
not
changed
since
the
last
comprehensive
product
chemistry
reviews
or
submit
complete
updated
product
chemistry
data
packages,
the
Branch
has
no
objections
to
the
reregistration
of
lindane
with
respect
to
product
chemistry
data
requirements.
Residue
Chemistry
The
Agency
will
not
require
a
new
confined
rotational
crop
study
provided
the
registrants
propose
a
30
day
plantback
interval
for
leafy
vegetables
and
a
12
month
plantback
interval
for
all
other
unregistered
crops
on
all
of
their
end
use
product
labels
for
lindane.
New
nature
of
the
residue
study
is
required
for
application
of
lindane
as
a
seed
treatment
to
a
cereal
grain.
If,
after
submission
of
an
acceptable
cereal
grain
seed
treatment
metabolism
study,
the
HED
Metabolism
Assessment
Review
Committee
determines
the
residues
of
concern
to
include
metabolites
in
addition
to
lindane,
additional
crop
field
trial
data,
magnitude
of
the
residue
in
poultry
and
cattle,
and
processing
studies
will
be
required.
In
addition,
an
adequate
residue
analytical
method
and
storage
stability
data
will
be
required.
48
| epa | 2024-06-07T20:31:43.024812 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0202-0002/content.txt"
} |
EPA-HQ-OPP-2002-0202-0003 | Supporting & Related Material | "2002-08-14T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
Office
of
Prevention,
Pesticides
and
Toxic
Substances
July
31,
2002
MEMORANDUM
SUBJECT:
Lindane;
Chemical
No.
009001.
Revised
Assessment
of
Risk
from
Use
of
Lindane
for
Treatment
of
Lice
and
Scabies
DP
Barcode:
D284188;
Submission
No.
S605841
Reregistration
Case
#:
0315
FROM:
Becky
Daiss
Environmental
Health
Scientist
Reregistration
Branch
4
Health
Effects
Division
(7509C)
THROUGH:
Susan
Hummel
Branch
Senior
Scientist
Reregistration
Branch
4
Health
Effects
Division
(7509C)
TO:
Mark
Howard
Reregistration
Branch
3
Special
Review
&
Reregistration
Division
(7508C)
This
provides
HED's
revised
assessment
of
risk
from
use
of
lindane
for
treatment
of
scabies
and
lice.
The
revised
assessment
incorporates
additional
information
and
comments
provided
by
the
Food
and
Drug
Administration
(FDA).
2
1.0
ASSESSMENT
OF
RISK
FROM
USE
OF
LINDANE
TO
TREAT
SCABIES
HED's
assessment
of
risk
from
use
of
lindane
to
treat
scabies
uses
data
from
both
animal
and
human
studies
and
provides
a
range
of
risk
estimates.
EPA
conducted
analyses
using:
1)
a
Margin
of
Exposure
(MOE)
approach
based
on
animal
toxicity
data,
and
2)
a
comparison
of
lindane
blood
levels
from
one
study
which
documents
cases
of
accidental
lindane
ingestion
by
toddlers
in
which
blood
levels
were
determined
after
ingestion,
and
a
second
study
which
provides
data
on
blood
levels
of
lindane
following
application
of
lindane
to
treat
scabies.
HED
based
its
assessment
on
directions
provided
in
the
current
label
for
scabies
treatment.
It
is
important
to
note,
however,
that
FDA
is
planning
to
make
a
number
of
changes
to
the
label
including
statements
that
restrict
the
use
to
patients
who
have
attained
adult
stature
(i.
e.,
>
60
kg
body
weight).
Therefore,
HED
also
considered
pending
label
changes
in
its
assessment
of
lindane
as
a
scabies
treatment.
1.1
MOE
Approach
Under
this
approach,
an
estimated
MOE
is
calculated
based
on
a
toxicological
endpoint
recommended
by
HED's
Hazard
Identification
and
Assessment
Committee
(HIARC)
and
compared
with
the
target
MOE
for
short
term
dermal
exposure/
risk
to
determine
whether
there
is
an
exposure
of
concern.
The
MOE
is
the
ratio
of
the
appropriate
No
Observed
Adverse
Effect
Level
(NOAEL)
to
estimated
exposure.
For
the
short
term
dermal
endpoint,
a
NOAEL
of
6
mg/
kg/
day
was
selected
from
an
acute
oral
neurotoxicity
study
in
rats.
For
residential
exposures,
uncertainty
factors
are
used
to
determine
target
MOEs.
The
target
MOE
for
exposure
to
lindane
from
pharmaceutical
use
is
100
based
on
uncertainty
factors
(UF)
used
to
account
for
differences
among
humans
(intraspecies
variability
UF
of
10),
and
for
differences
between
the
test
animals
and
humans
(interspecies
extrapolation
UF
of
10).
Since
the
NOAEL
is
based
on
an
oral
toxicity
study,
dermal
absorption
data
are
required
to
adjust
the
oral
dose.
Two
different
dermal
absorption
factors
were
used
to
calculate
estimated
exposure.
One
was
taken
from
a
1989
article
published
in
Journal
of
Toxicological
and
Environmental
Health,
which
reported
data
from
a
dermal
absorption
study
on
rhesus
monkeys
to
determine
if
lindane
applied
for
treatment
of
lice
and
scabies
is
absorbed
into
the
blood
stream
(1).
A
second
was
taken
from
a
study
in
Toxicology
and
Applied
Pharmacology,
1974,
in
which
lindane
was
tested
on
human
subjects
to
quantify
dermal
penetration
(2).
The
monkey
study
involved
topical
application
of
1%
lotion,
at
label
prescribed
rates,
to
the
forehead,
forearm,
or
forepaw
of
monkeys
for
24
hours.
Percent
absorption
was
determined
based
on
urinary
excretion
of
14
C
lindane.
Study
results
indicated
that
18,
34,
and
54%
of
the
applied
dose
was
absorbed
after
application
to
the
forearm,
forehead,
and
palm,
respectively.
A
weighted
average
of
20%
was
derived
based
on
the
body
surface
area
corresponding
to
the
applicable
dermal
absorption
factor
from
the
monkey
study.
For
the
human
study,
C
14
labeled
lindane
was
applied
topically
(4
g/
cm
2
)
to
the
forearm
and
via
the
intravenous
route
(1
Ci).
Excretion
of
the
chemical
was
then
monitored
by
collecting
3
and
analyzing
urine
samples
during
the
5
day
testing
period.
All
results
were
calculated
as
percent
of
the
injected
or
applied
dose.
Data
from
the
IV
dosing
was
used
to
correct
the
skin
penetration
data
for
incomplete
urinary
recovery.
Lindane
was
shown
to
have
a
dermal
penetration
factor
of
9.3%
±
3.
7
(SD).
Results
of
the
scabies
MOE
assessment
for
children
and
young
adults
using
both
monkey
and
human
dermal
absorption
data
are
provided
in
Tables
1
and
2
respectively.
The
analysis
indicates
MOEs
of
concern
(MOE<
100)
from
both
high
and
low
end
treatment
scenarios.
Table
1.
Assessment
of
Use
of
Lindane
for
Scabies
DAF
from
Product
Specific
Monkey
Study
Age
Group
Oral
NOAEL
(mg/
kg/
d)
Applied
Dose
(mg)
1
Body
Weight
(kg)
2
Daily
Dermal
Dose
(mg/
kg/
d)
dermal
absorption
(%)
MOE
Target
MOE
3
Young
Adult
6
600
high
end
(1
oz)
60
10
20
3
100
Young
Adult
6
300
low
end
(2
oz)
60
5
20
6
100
Child
4
6
6
250
high
end
22
11
20
3
100
Child
4
6
6
150
low
end
22
7
20
4
100
Toddler
1
3
6
200
high
end
13
15
20
2
100
Toddler
1
3
6
100
low
end
13
8
20
4
100
MOE
=
Oral
NOAEL(
mg/
kg/
day)
daily
dermal
dose
(mg/
kg/
day)
x
dermal
absorption
factor
(%)
where:
Daily
Dermal
Dose
=
applied
dose
(mg)
÷
body
weight
(kg)
Applied
Dose
=
20
60g
of
1%
lotion
(high
end);
10
30
g
of
1%
lotion
(low
end)
depending
on
age
group
Dermal
Absorption
Factor
=
20%
(weighted
avg)
where:
Palm
Dermal
Absorption
Factor
=
54%
DAF
from
monkey
study;
Used
for
hands
which
are
assumed
to
be
6%
of
Dosed
Body
Surface
Area
based
on
%
of
Surface
Area/
Body
Part
from
EPA
Exposure
Factor
Handbook
(EFH)
Vol
I
Forearm
Dermal
Absorption
Factor
=
18%
DAF
from
monkey
study;
Used
for
94%
of
Dosed
Body
Surface
Area
(all
but
hands)
based
on
%
of
Total
Surface
Area/
Body
Part
from
EPA
EFH
Vol
I
Dosed
Body
Surface
Area
=
entire
body
from
neck
down
Table
2.
Assessment
of
Lindane
for
Scabies
DAF
from
Pesticide
Exposure
in
Human
Study
Age
Group
Oral
NOAEL
(mg/
kg/
d)
Applied
Dose
(mg)
1
Body
Weight
(kg)
2
Daily
Dermal
Dose
(mg/
kg/
d)
dermal
absorption
(%)
MOE
Target
MOE
3
Young
Adult
6
600
high
end
60
10
10
6
100
Young
Adult
6
300
low
end
60
5
10
12
100
Child
4
6
6
250
high
end
22
11
10
5
100
Child
4
6
6
150
low
end
22
7
10
9
100
Toddler
1
3
6
200
high
end
13
15
10
4
100
Toddler
1
3
6
100
low
end
13
8
10
8
100
MOE
=
Oral
NOAEL(
mg/
kg/
day)
daily
dermal
dose
(mg/
kg/
day)
x
dermal
absorption
factor
(%)
where:
Daily
Dermal
Dose
=
applied
dose
(mg)
÷
body
weight
(kg)
Applied
Dose
=
20
60
g
of
1%
lotion
(high
end);
10
30
g
of
1%
lotion
(low
end)
depending
on
age
group
Dermal
Absorption
Factor
=
10%
from
human
pesticide
application
dermal
absorption
study
1
Application
rates
are
based
on
pending
label
for
young
adults
and
current
label/
estimated
body
sizes
for
small
children.
2
Young
adult
BW
is
based
on
pending
label
changes.
Child
and
toddler
BW
is
avg
from
EPA
EFH
3
Does
not
include
an
FQPA
safety
factor
which,
if
applied,
would
increase
the
Target
MOE
to
300
for
infants
and
children
4
Uncertainties
Associated
with
the
MOE
Assessment
Toxicity
Endpoint
The
toxicity
endpoint
used
in
the
MOE
assessment
is
based
on
an
acute
oral
neurotoxicity
study
where
the
test
material
was
administered
by
gavage.
An
oral
gavage
dose
may
be
absorbed
more
rapidly
than
the
dermal
dose,
producing
a
higher
peak
concentration
of
lindane
in
the
blood
and
target
tissues
than
a
dermal
dose.
Use
of
a
toxicity
endpoint
based
on
an
oral
dose
(adjusted
to
reflect
10%
or
20%
dermal
absorption)
may
therefore
overestimate
toxicity
from
a
dermal
dose.
Since
adult
animals
were
used
in
the
acute
oral
study
and
children
are
more
susceptible
to
exposure
than
adults,
use
of
a
toxicity
endpoint
based
on
the
acute
study
may
underestimate
risks
to
children
who
are
exposed
to
lindane.
Dermal
Absorption
HED
calculated
MOEs
assuming
20%
and
10%
dermal
absorption.
The
20%
absorption
value
is
derived
from
a
study
of
the
absorption
of
the
scabies
lotion
applied
to
monkeys.
The
lotion
was
left
on
for
24
hours
in
the
monkey
assessment
and
therefore
may
overestimate
dermal
absorption
for
scabies
treatment,
which
has
a
12
hour
exposure
duration
limit
based
on
label
restrictions.
In
addition,
monkeys
may
not
absorb
the
scabies
lotion
in
the
same
manner
as
humans.
The
10%
absorption
values
is
from
a
study
of
absorption
of
pesticides
applied
to
humans.
Humans
may
absorb
the
pesticide
and
lotion
formulations
at
different
rates.
Since
there
are
no
data
to
evaluate
the
relative
absorption
of
the
scabies
lotion
by
monkeys
vs.
humans
or
the
relative
absorption
by
humans
of
the
pesticide
vs.
scabies
lotion,
it
is
not
possible
to
assess
whether
these
dermal
absorption
factors
tend
to
overstate
or
understate
potential
risk.
However,
use
of
both
studies
provides
a
range
of
dermal
absorption
and
probably
provides
an
adequate
bounding
of
potential
exposure.
Anticipated
Label
Changes
According
to
the
FDA,
the
label
for
the
1%
scabies
treatment
lotion
will
be
revised
to
restrict
use
to,
"patients
who
have
attained
adult
stature,
or
approximately
60
kg".
The
label
will
also
be
revised
to
recommend
only
that
a
thin
layer
of
lotion
be
applied.
The
current
label
prescribes
the
following;
"Use
only
enough
to
cover
the
body
in
a
thin
layer.
1
ounce
(half
a
2
ounce
container)
should
be
all
that
is
needed
for
children
under
6
years
of
age:
1
2
ounces
for
older
children
and
adults".
HED
conducted
its
scabies
MOE
assessment
based
on
directions
provided
in
the
current
label.
Given
anticipated
label
changes,
use
in
accordance
with
the
revised
label
would
eliminate
risks
to
young
children
(less
than
60
kg).
Also,
according
to
FDA,
pending
label
changes
to
the
amount
of
lotion
required
should
result
in
lower
application
rates
for
both
older
children
and
adults.
1.
2
Blood
Level
Comparison
in
Children
HED
also
analyzed
potential
risk
from
lindane
used
as
a
scabies
treatment
based
on
data
on
lindane
blood
levels
provided
in
two
published
literature
studies.
One
study
documents
cases
of
accidental
lindane
ingestion
by
toddlers
in
which
blood
levels
were
determined
after
ingestion.
The
second
study
provides
data
on
blood
levels
of
lindane
in
children
after
application
of
1%
5
lindane
lotion
to
treat
scabies.
The
blood
level
associated
with
acute
accidental
ingestion
which
resulted
in
short
term
adverse
effects
according
to
the
accidental
ingestion
case
study
is
0.32
ug/
mL.
The
highest
measured
blood
concentration
from
the
clinical
study
of
levels
associated
with
prescribed
uses
of
lindane
to
treat
scabies
was
0.064
ug/
mL.
The
studies
are
described
in
more
detail
below.
Acute
Accidental
Lindane
Ingestion
Case
reports
published
in
the
November,
1995,
edition
of
the
Annals
of
Emergency
Medicine
provide
data
on
blood
levels,
adverse
effects,
and
time
and
level
of
recovery
resulting
from
acute
accidental
lindane
ingestion
in
toddlers.(
3)
As
noted
in
the
Annals
publication,
most
cases
reported
in
the
literature
involve
dermal
lindane
toxicity;
ingestion
toxicity
is
infrequently
documented
and
data
on
blood
levels
associated
with
ingestion
are
rare.
The
article
presents
three
cases
in
which
blood
levels
were
obtained
and
documented
after
ingestion.
The
highest
lindane
blood
concentrations
documented
in
the
case
studies
in
which
the
patient
exhibited
full
recovery
was
0.
32
ug/
mL
(Case
1).
This
case
involved
a
13
month
old
boy
who
accidently
ingested
part
of
the
contents
of
a
bottle
of
Kwell
lotion.
The
following
description
of
Case
1
is
excerpted
from
the
1995
article.
In
this
case,
a
13
month
old
boy
was
brought
to
a
local
emergency
department
after
being
found
with
an
open
bottle
of
Kwell
lotion.
He
was
described
as
glassy
eyed,
he
vomited
twice,
and
had
a
generalized
tonic
clonic
seizure.
The
child
was
transported
to
the
hospital
where
he
was
somnolent.
Shortly
after
arrival,
he
had
another
seizure.
He
was
treated
and
laboratory
analyses
were
conducted.
Blood
lindane
concentrations
were
determined
with
the
method
of
Dale
et
al
in
accordance
with
Environmental
Protection
Agency
procedures.
The
lindane
level
was
0.
32
ug/
mL
(4
hours
after
ingestion)
and
0.
02
ug/
mL
(20
hours
after
ingestion).
The
child
was
transferred
to
a
children's
hospital
ICU,
where
his
mental
status
progressively
improved.
The
next
day
the
child
had
slightly
decreased
activity.
During
observation
over
the
next
2
days
his
condition
progressively
improved,
and
he
was
discharged
home.
The
Physicians
Desk
Reference
(PDR)
provides
the
following
statement
on
clinical
pharmacology
regarding
1%
lindane
cream,
"Dale,
et
al
reported
a
blood
level
of
290
ng/
ml
associated
with
convulsions
following
the
accidental
ingestion
of
a
lindane
containing
product".
Lindane
Blood
Levels
in
Children
Following
Application
of
1%
Lotion
for
Scabies
A
1977
article
in
The
Journal
of
Pediatrics
provides
data
from
a
study
conducted
in
the
Acute
Care
Clinic
of
Children's
Medical
Center,
Dallas,
Texas
which
documents
blood
levels
of
lindane
in
infants
and
children
who
were
treated
with
1%
lindane
lotion
for
scabies.
(4)
6
In
this
study,
serum
concentrations
of
lindane
were
determined
in
infants
and
children
with
and
without
scabies
infection
following
application
of
1%
lindane
lotion.
Studies
were
performed
in
20
infected
and
noninfected
patients
who
averaged
33
to
64
months
of
age
with
average
weights
ranging
from
13
to
17
kg.
After
a
pretreatment
blood
sample
was
obtained,
1%
lindane
product
was
applied
to
the
body
surface
area
prescribed
by
the
label.
Twenty
four
hours
after
application
of
the
lotion,
all
patients
were
given
a
warm
soapy
bath.
The
current
label
for
lindane
lotion
applied
for
scabies
specifies
that
the
lotion
should
not
be
left
on
for
more
than
12
hours.
This
may
result
in
an
overestimation
of
blood
concentrations,
however,
it
is
likely
not
relevant
to
the
risk
assessment
since
the
blood
level
measured
at
6
hours
was
used
for
risk
assessment
purposes.
Specimens
of
blood
for
determination
of
lindane
concentrations
were
obtained
at
0,
2,
4,
6,
8,
12,
24,
and
48
hours
after
topical
application
of
1%
lotion.
Patient
characteristics
are
presented
in
Table
3
and
results
are
presented
in
Table
4.
TABLE
3.
Characteristics
of
Scabies
Treatment
Patients
Infected
Non
Infected
No.
patients
12
8
Mean
Age
(months)
33
64
Mean
Weight
(kg)
13
17
Dose
of
1%
lotion
(mg)
44
57
TABLE
4.
Blood
Concentrations
of
Lindane
After
Scabies
Treatment
Concentrations
of
Lindane
in
Blood
(ug/
ml)
Time
(hr)
Infected
Noninfected
Avg
Range
Avg
Range
2
0.
013
0.005
0.038
0.007
0.001
0.017
4
0.
025
0.007
0.048
0.013
0.008
0.027
6
0.
028
0.013
0.039
0.024
0.007
0.064
8
0.
026
0.010
0.037
0.019
0.009
0.040
12
0.023
0.002
0.043
0.015
0.002
0.033
24
0.010
0.003
0.019
0.013
0.006
0.024
36
0.008
0.002
0.012
0.009
0.004
0.018
48
0.006
0.001
0.021
0.005
0.002
0.008
Blood
half
life
17.9
hr
21.4
hr
Discussion
of
Uncertainties
Associated
with
Blood
Level
Analysis
Allowable
Blood
Level
in
Children
(i.
e.,
non
exceedance
levels
based
on
evidence
of
adverse
effects)
It
is
uncertain
whether
the
levels
of
320
ng/
mL
and
290
ng/
mL
represent
the
maximum
levels
of
lindane
in
the
subjects'
blood.
Given
that
the
measured
level
of
320
ng/
mL
in
the
cited
clinical
study
was
taken
at
least
4
hours
after
ingestion,
it
is
likely
that
initial
blood
levels
were
higher.
It
is
also
uncertain
what
blood
level
is
associated
with
the
effects
observed
in
the
case
study
patient.
To
the
extent
that
observed
effects
are
attributable
to
higher
than
measured
lindane
blood
levels,
the
assessment
tends
to
overstate
potential
risk.
To
the
extent
that
adverse
effects
may
be
associated
with
lindane
blood
levels
lower
than
320
ng/
mL,
the
assessment
may
tend
to
underestimate
risk.
7
The
subjects
in
the
clinical
study
received
a
bath
with
warm
soapy
water
prior
to
application
of
the
lindane
lotion.
Wet
skin
tends
to
exhibit
greater
dermal
absorption
than
dry
skin.
Use
of
the
blood
levels
from
the
study
may
therefore
overstate
potential
exposure
for
individuals
who
have
dry
skin
at
the
time
of
application.
In
the
clinical
study,
the
lindane
lotion
was
left
on
for
24
hours
after
application.
The
current
label
for
scabies
treatment
specifies
that
the
lotion
should
not
be
left
on
for
more
than
12
hours.
This
prolonged
exposure
may
result
in
an
overestimation
of
blood
concentrations
seen
after
12
hours.
However,
it
should
not
effect
the
6
hour
peak
level
used
in
the
risk
assessment.
The
potential
contribution
of
other
lotion
components
to
observed
effects
is
not
known.
Anticipated
Label
Changes
Based
on
the
average
age,
the
clinical
scabies
study
looked
only
at
infants
and
small
children
(up
to
8
yrs
old).
Average
amounts
of
lindane
applied
in
the
study
were
129
158
mg.
Given
that
the
current
label
prescribes
up
to
300
mg
(1
oz)
for
infants
and
up
to
600
mg
(2
oz)
for
children
6
and
older,
the
amount
of
product
applied
in
the
study
was
2
4
times
less
than
the
currently
allowable
amount.
However,
the
label
for
the
1%
scabies
lotion
will
be
revised
to
prescribe
against
use
of
the
product
for
small
children
(i.
e.,
children
less
than
60
kg).
Given
anticipated
label
changes,
use
in
accordance
with
the
revised
label
would
eliminate
risks
to
young
children
(<
60
kg).
Also,
according
to
FDA,
pending
label
changes
on
the
amount
of
lotion
required
should
result
in
lower
application
rates
for
both
older
children
and
adults.
Although
there
is
insufficient
data
to
indicate
a
correlation
between
amount
applied
dermally
and
corresponding
blood
levels,
it
is
reasonable
to
assume
that
use
of
a
lower
amount
of
product
will
produce
lower
lindane
blood
levels.
Finally,
the
new
label
will
direct
that
lindane
be
applied
to
dry
skin
which
will
reduce
the
amount
of
lindane
absorbed
into
the
blood
stream.
Children
vs.
Adults
The
blood
level
comparison
analysis
pertains
and
is
applicable
only
to
small
children.
HED
has
no
data
on
blood
levels
associated
with
adverse
effects
in
adults
nor
do
we
have
data
on
blood
levels
associated
with
prescribed
use
of
lindane
to
treat
scabies
in
adults.
Based
on
available
toxicity
data,
children
are
more
sensitive
than
adults.
Therefore
adverse
effects
would
occur
at
higher
blood
levels
in
adults
and
older
children
than
in
young
children.
In
addition,
blood
levels
associated
with
prescribed
use
(under
both
current
and
revised
labels)
would
be
lower
in
older
children
and
adults
due
to
differences
in
weight
to
body
surface
area
ratios
between
young
children
and
adults/
young
adults.
1.3
HED
Conclusions
HED's
analysis
using
the
MOE
approach
indicates
MOEs
of
concern
from
both
high
and
low
end
treatment
scenarios
for
all
ages
assessed
using
either
monkey
or
human
dermal
absorption
data.
For
the
blood
concentration
analysis,
HED
compared
blood
concentrations
from
the
scabies
study
with
the
blood
concentration
associated
with
short
term
adverse
effects
in
children.
HED
is
concerned
that
there
is
an
inadequate
margin
of
safety
between
the
blood
levels
associated
with
scabies
treatment
(0.
064
ug/
mL)
and
the
blood
levels
resulting
in
short
term
8
effects
in
children
(0.
29
0.
32
ug/
mL).
Given
variability
of
responses
in
humans,
an
uncertainty
factor
of
10
is
considered
reasonable
for
this
risk
assessment.
There
is
a
4
5
fold
difference
between
blood
levels
in
treated
patients
and
allowable
blood
levels
identified
based
on
evidence
of
adverse
effects.
While
this
assessment
does
consider
mitigation
efforts
being
undertaken
by
FDA,
it
is
important
to
note
that
it
does
not
consider
the
medical
benefits
of
scabies
treatment.
1.
4
FDA
Assessment
and
Conclusions
FDA
will
approve
a
drug
that
it
finds
is
safe
and
effective
for
a
specific
population
with
a
specific
condition
when
the
drug
is
used
in
accordance
with
its
proposed
labeling.
Safe
and
effective
does
not
mean
without
risks,
it
means
that
the
benefit
of
the
treatment
outweighs
the
risk
for
the
patient
group
specified
in
the
label.
As
described
below,
FDA
conducted
a
risk/
benefit
analysis
of
the
use
of
lindane
as
second
line
prescription
medication
for
scabies
and
concluded,
based
on
that
analysis,
that
lindane
is
safe
and
effective
for
treatment
of
scabies
when
used
in
a
manner
consistent
with
its
labeling.
Second
line
therapy
is
defined
as
a
product
that
should
be
used
only
if
another
treatment
has
already
failed,
or
if
the
patient
cannot
tolerate
another
available
therapy.
Risks
Lindane
has
been
on
the
market
since
1947,
but
was
labeled
a
second
line
therapy
in
1995
after
review
by
the
FDA.
It
is
similar
in
action
to
other
approved
therapies,
but
has
a
higher
percutaneous
absorption
than
other
approved
scabicides
and
pediculocides.
This
greater
systemic
exposure
may
translate
to
a
greater
potential
for
serious
adverse
events,
such
as
seizure.
This
systemic
exposure
can
be
exaggerated
in
patients
with
an
immature
or
compromised
cutaneous
barrier.
Animal
data
have
demonstrated
that
the
young
are
more
sensitive
to
the
neurotoxic
effects
of
lindane.
FDA
assessed
the
safety
and
potential
risks
from
use
of
lindane
as
a
drug
based
on
safety
information
from
the
spontaneous
adverse
event
reporting
system
(AERS)
and
current
literature.
The
AERS
database
is
a
collection
of
spontaneous,
voluntarily
submitted
reports
of
adverse
events
associated
with
drug
products
submitted
by
consumers,
healthcare
professionals,
manufacturers,
and
others.
One
of
the
limitations
of
a
voluntary
system
of
reporting
is
a
substantial
amount
of
under
reporting.
FDA
estimates
that
between
one
and
10%
of
all
adverse
events
are
reported
to
FDA.
Other
limitations
include
the
variability
in
the
quality
and
quantity
of
information
reported.
In
spite
of
known
limitations,
the
spontaneous
system
has
value.
The
system
is
sensitive
to
rare,
unexpected
events,
is
simple
to
use,
and
is
relatively
inexpensive.
However,
the
AERS
database
does
not
include
the
total
number
of
patients
who
have
been
treated,
with
or
without
adverse
events.
Because
of
this,
it
is
not
possible
to
quantify
the
percentage
of
patients
who
have
had
adverse
events.
Most
of
the
serious
adverse
events
in
the
AERs
database
occurred
in
patients
who
had
already
labeled
contraindications
to
the
use
of
lindane,
who
used
lindane
in
excessive
amounts,
or
who
ingested
lindane.
9
Moreover,
even
though
there
appears
to
be
a
narrow
therapeutic
index,
there
isn't
much
evidence
that
labeled
use
leads
to
serious
adverse
events.
The
290
ng/
ml
plasma
level
in
the
Physician's
Desk
Reference
(PDR)
and
the
320
ng/
ml
plasma
level
from
the
Aks
article
are
plasma
levels
that
were
obtained
several
hours
after
acute
ingestion
of
the
lindane
product.
The
two
levels
are
from
pediatric
patients
who
ingested
lindane
and
had
seizures.
This
information
is
helpful
to
a
physician
in
determining
if
the
patient's
seizure
was
secondary
to
lindane
ingestion,
or
if
there
is
another
etiology.
The
plasma
levels
may
provide
a
tool
to
determine
the
etiology
of
a
patient's
seizure
upon
presentation
to
the
Emergency
Room
but
are
not
a
"No
observed
adverse
event
level
(NOAEL)."
The
data
for
lindane
indicate
that
there
is
a
two
compartment
pharmacokinetic
model.
After
ingestion,
there
is
a
steep
rise
in
the
serum
level,
followed
by
a
rapid
decline
during
the
disposition
phase
when
some
lindane
distributes
to
lipid
tissues
and
some
is
excreted.
The
disposition
phase
is
followed
by
a
prolonged
beta
elimination
phase.
Based
on
this
model,
it
is
probable
that
the
patients'symptoms
(seizure)
occurred
at
a
higher
serum
level
than
those
levels
obtained
4
hours
after
the
initial
ingestion.
In
addition,
the
marketed
formulation
contains
other
ingredients
that
may
contribute
to
the
toxicity
in
acute
ingestions.
Ingredients
for
lotion
include:
glycerol
monostearate,
cetyl
alcohol,
stearic
acid,
trolamine,
carrageenan,
2
amino
2
methyl
1propanol
methylparaben,
butylparaben,
perfume
and
water.
Ingredients
for
shampoo
include:
trolamine
lauryl
sulfate,
polysorbate
60,
acetone
and
water
It
is
important
to
emphasize
that
the
blood
levels
listed
in
the
PDR
and
the
article
by
Aks
are
single
cases
following
ingestion
by
toddlers
of
an
unknown
quantity
of
lindane.
The
young
do
appear
to
be
more
sensitive
to
the
neurotoxic
effects
of
lindane,
as
seen
in
studies
across
species.
The
serum
lindane
level
that
may
lead
to
a
seizure
in
a
small
child
is
most
likely
lower
than
the
level
that
would
cause
an
equal
effect
in
an
adult.
The
labeling
is
being
changed
to
reflect
this
concern,
indicating
that
lindane
should
be
used
only
in
patients
who
have
achieved
adult
stature,
or
approximately
60
kilograms.
Benefits
FDA
recognizes
that
all
drugs
have
associated
risks.
Therefore,
FDA
must
determine
if
the
potential
risks
of
adverse
side
effects
associated
with
a
drug
treatment
outweigh
the
overall
health
benefits
of
treating
the
condition.
Although
not
life
threatening,
scabies
can
pose
significant
problems
if
left
untreated,
including
severe
itching
and
secondary
infections.
In
underdeveloped
areas
of
the
world
where
treatments
are
not
available
or
medical
care
is
inaccessible,
scabies
can
be
pandemic
and
accounts
for
significant
morbidity.
FDA
has
concluded
that
there
is
no
question
that
the
standard
of
care
for
these
patients
is
to
administer
scabicidal
treatment
for
their
infestation.
FDA
considers
alternative
therapies
when
evaluating
the
benefit
of
a
drug.
Although
the
FDA
has
determined
that
there
are
other
products
for
the
treatment
of
scabies
that
may
have
less
risk
and
should
be
used
first
in
a
patient,
FDA
also
recognizes
that
there
are
patients
"who
have
10
either
failed
to
respond
to
adequate
doses,
or
are
intolerant
of,
other
approved
therapies."
These
patients
would
have
documented
failed
prior
treatment
with
other
approved
products,
or
documented
reactions
–
either
local
or
systemic,
to
those
products
or
drugs
that
would
be
expected
to
cross
react
with
those
products.
Although
there
are
other
therapies
available
for
first
line
use
in
the
treatment
of
scabies,
FDA
believes
it
is
in
the
best
interest
of
public
health
to
have
several
alternatives
available
for
this
subset
of
patients.
The
approved
treatment
options
for
scabies
are
limited.
They
are:
permethrin
cream,
5%
(Acticin
and
Elimite),
lindane
cream
1%
(not
marketed
in
the
U.
S.),
lindane
lotion
1%,
and
crotamiton
cream
(Eurax).
Precipitated
sulfur
ointment,
5
10%,
is
occasionally
compounded
and
used
for
scabies.
For
safety
reasons,
crotamiton
and
precipitated
sulfur
ointment
are
reasonable
options
for
young
children
and
pregnant
women,
but
the
efficacy
of
these
products
is
much
lower
than
other
products,
and
re
treatment
is
frequently
necessary.
There
is
information
available
on
the
internet
about
other
alternative
treatments
that
include
soaking
in
borax.
The
efficacy
of
these
therapies
is
unknown.
Resistance
to
products
must
also
be
considered
when
evaluating
drugs.
There
are
currently
only
three
approved
treatments
for
scabies,
and
as
mentioned
earlier,
crotamiton
is
not
as
effective
as
lindane
or
permethrin.
Lindane
is
labeled
for
second
line
therapy
and
should
only
be
used
in
the
event
that
there
is
treatment
failure
or
if
the
patient
is
intolerant
to
the
other
two
treatments.
If
a
patient
has
persistent
infestation
after
one
form
of
treatment,
there
should
first
be
an
assessment
for
appropriate
use,
and
if
it
is
determined
that
the
failure
wasn't
due
to
misuse,
then
the
patient
should
be
retreated
with
an
alternative
agent.
There
is
a
public
health
benefit
to
having
several
treatment
options
for
a
condition
where
a
patient
may
require
re
treatment
with
a
different
therapy,
especially
when
there
may
be
emerging
or
transient
resistance.
Lindane
has
been
available
since
1947,
and
there
are
some
case
reports
that
the
scabies
mite
has
recently
developed
resistance
to
it.
A
literature
search
did
not
reveal
any
reports
of
scabies
mite
resistance
to
permethrin,
but
it
has
been
on
the
market
for
a
much
shorter
period
of
time
than
lindane.
There
is
one
case
report
in
the
literature
of
resistance
to
crotamiton.
It
is
not
unreasonable
to
expect
that
resistance
to
permethrin
will
develop
over
time.
If
this
resistance
does
occur,
and
lindane
is
not
available,
physicians
would
not
have
alternative
approved
and
effective
therapies
for
patients
infested
with
scabies.
Conclusions
FDA
has
concluded
that
lindane
is
safe
and
effective
for
treatment
of
scabies
when
used
in
a
manner
consistent
with
its
labeling.
Although
lindane
is
already
labeled
as
a
second
line
therapy,
the
current
label
is
being
revised
to
indicate
that
lindane
is
for
use
only
in
patients
who
have
attained
adult
stature
(approximately
60
kilograms).
This
emphasizes
that
it
should
not
be
used
in
young
pediatric
patients,
and
that
patients
should
be
post
pubescent.
In
addition,
physicians
are
11
instructed
to
use
caution
when
they
are
prescribing
this
product
to
patients
who
have
underlying
conditions
(HIV/
AIDS)
or
are
on
medications
that
may
result
in
a
lowered
seizure
threshold,
and
patients
who
have
skin
conditions
that
may
allow
enhanced
absorption.
Extensive
information
will
be
provided
for
the
physician
and
the
patient
regarding
the
potential
risk
of
applying
the
product
more
than
once.
The
new
label
also
includes
a
medication
guide
that
must,
by
law,
be
given
to
each
patient
with
the
lindane
prescription.
This
medication
guide
explains
in
plain
language
the
potential
for
harm
if
the
lindane
is
used
other
than
as
instructed.
It
also
includes
clear
instructions
for
use.
The
high
volume
container
sizes
are
being
discontinued
to
limit
the
amount
per
prescription.
It
is
anticipated
that
this
will
decrease
over
use
the
product.
2.0
ASSESSMENT
OF
RISK
FROM
USE
OF
LINDANE
TO
TREAT
LICE
HED's
assessment
of
risk
from
use
of
lindane
to
treat
head
lice
relies
on
data
provided
in
two
published
literature
studies.
One
study
documents
cases
of
accidental
lindane
ingestion
by
toddlers
in
which
blood
levels
were
determined
after
ingestion.
The
second
study
provides
data
on
blood
levels
of
lindane
in
children
and
young
adults
following
application
of
Kwell
Shampoo
to
treat
head
lice.
2.
1
Blood
Level
Comparison
in
Children
Acute
Accidental
Lindane
Ingestion
in
Toddlers
See
case
study
and
PDR
data
described
above
for
scabies
assessment.
(3)
Absorption
of
Lindane
Following
Application
of
Kwell
Shampoo
to
Treat
Lice
EPA
has
a
published
study
on
blood
levels
of
lindane
in
children
and
young
adults
following
standard
application
of
Kwell
Shampoo.
An
1983
article
in
Pediatric
Dermatology
provides
data
from
a
study
conducted
in
the
Outpatient
Clinic
of
Children's
Medical
Center,
Dallas,
Texas.
(4)
In
this
study,
serum
concentrations
of
lindane
were
determined
in
children
with
pediculosis
capititis
following
application
of
1%
Kwell
shampoo.
Studies
were
performed
in
9
patients
who
were
from
3.5
to
18
years
of
age
with
weights
ranging
from
13.6
to
35
kg,
and
heights
ranging
from
99
to
163
cm.
After
a
pretreatment
blood
sample
was
obtained,
1%
lindane
product
was
applied
to
dry
hair
using
a
sufficient
amount
of
medication
to
thoroughly
saturate
the
hair
and
scalp.
After
10
minutes,
small
quantities
of
water
were
added
until
a
lather
formed.
Shampooing
was
continued
for
an
additional
4
minutes
after
which
the
hair
was
rinsed
and
blown
dry
with
a
hair
dryer.
The
current
label
for
Kwell
shampoo
specifies
that
the
shampoo
should
remain
in
place
on
dry
hair
for
4
minutes
only
before
water
is
added
to
form
lather.
Consequently,
the
study
may
result
in
higher
absorption
than
would
occur
following
label
directions.
Four
patients
were
12
retreated
because
of
persistence
of
living
lice
after
5
days.
Specimens
of
blood
were
obtained
at
0,
2,
4,
6,
and
24
hours
after
topical
application
of
Kwell
shampoo.
Patient
characteristics
are
presented
in
Table
5
and
results
are
presented
in
Table
6.
TABLE
5.
Characteristics
of
the
Lice
Patients
Initial
Treatment
Retreatmemt
No.
patients
8
4
Mean
Age
(years)
7.8
8.
1
Mean
Weight
(kg)
27
29
Mean
Height
(cm)
122
124
Dose
of
1%
GBH
Shampoo
(mL)
44
57
Calculated
Dose
of
lindane
(mg)
420
530
TABLE
6.
Blood
Concentrations
of
Lindane
After
Lice
Treatment
Mean
Concentrations
of
Lindane
in
Blood
(ng/
mL)
Time
(hr)
Initial
Treatment
Retreatment
Avg
Range
Avg
Range
0
0
0.29
0.25
0.3
2
1.
4
0.43
2.53
3.6
3.
26
3.88
4
0.
96
0.
38
1.52
3.3
1.
75
6.13
6
0.
72
0.
29
1.05
2.1
1.
64
2.64
24
0.41
0.26
0.69
1.1
0.
81
1.33
Discussion
of
Uncertainties
Associated
with
Blood
Level
Analysis
It
is
uncertain
whether
the
levels
of
320
ng/
mL
and
290
ng/
mL
represent
the
maximum
levels
of
lindane
in
the
subjects'
blood.
Given
that
the
measured
level
of
320
ng/
mL
in
the
cited
clinical
study
was
taken
at
least
4
hours
after
ingestion,
it
is
likely
that
initial
blood
levels
were
higher.
It
is
uncertain
what
blood
level
is
associated
with
the
effects
observed
in
the
case
study
patient.
To
the
extent
that
observed
effects
are
attributable
to
higher
than
measured
lindane
blood
levels,
the
assessment
tends
to
overstate
potential
risk.
To
the
extent
that
adverse
effects
may
be
associated
with
lindane
blood
levels
of
320
ng/
mL
or
lower,
the
assessment
may
tend
to
underestimate
risk.
The
current
label
for
Kwell
shampoo
specifies
that
the
shampoo
should
remain
in
place
on
dry
hair
for
4
minutes
only
before
water
is
added
to
form
lather.
In
the
clinical
study,
the
shampoo
was
left
in
place
for
10
minutes
before
water
was
added.
Consequently,
the
study
may
result
in
higher
absorption
than
would
occur
following
label
directions.
2.2
HED
Conclusions
The
highest
measured
blood
concentration
obtained
following
single
and
double
treatments
of
head
lice
at
label
rates
but
at
longer
than
label
specified
treatment
durations
was
0.00613
ug/
mL.
This
is
significantly
lower
than
0.32
ug/
mL,
the
blood
level
associated
with
acute
accidental
ingestion
which
resulted
in
short
term
adverse
effects
according
to
the
cited
case
study
13
article.
Therefore,
HED
does
not
believe
that
lindane
pharmaceutical
products
used
for
treatment
of
lice
pose
human
health
risks
of
concern
when
used
in
accordance
with
directions
provided
on
the
label.
2.
3
FDA
Assessment
Based
on
its
assessment
of
safety
and
potential
risks
from
use
of
lindane
as
a
prescription
medication
for
scabies
and
lice,
FDA
has
concluded
that
lindane
is
safe
and
effective
for
treatment
of
lice
when
used
as
labeled.
14
References
(1)
Moody,
R.
P.,
and
Ritter,
L.,
J.
Tox
and
Env
Hlth,
28:
161
169,
1989
(2)
Feldman,
R.
J.
and
Maibach,
H.
I.,
Tox
and
Applied
Pharmacology
28,
126
132,
1974
(3)
Aks,
S.
E.,
KrantzA.,
Hryhorczuk,
D.
O.,
Wagner,
S.,
andMock,
J.,
AnnEmergMed,
26:
647
651,
1995
(4)
Ginsburg,
C.
M.
and
Lowry,
W.,
Pediatric
Dermatology
Vol
1.
No.
1
74
76,
1983
| epa | 2024-06-07T20:31:43.045233 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0202-0003/content.txt"
} |
EPA-HQ-OPP-2002-0202-0004 | Supporting & Related Material | "2002-08-14T04:00:00" | null | December
13,
2001
MEMORANDUM
SUBJECT:
Lindane
(009001)
Reregistration
Case
No.
0315.
Revised
Anticipated
Residues,
Acute
and
Chronic
Dietary
Exposure
and
Risk
Analyses
for
the
HED
Human
Health
Risk
Assessment.
DP
Barcode
D279260.
FROM:
Thurston
G.
Morton,
Chemist
Reregistration
Branch
4
Health
Effects
Division
(7509C)
THROUGH:
David
Soderberg,
Chemist
Sheila
Piper,
Chemist
Dietary
Exposure
Science
Advisory
Council
and
Susan
V.
Hummel,
Branch
Senior
Scientist
Reregistration
Branch
4
Health
Effects
Division
(7509C)
TO:
Rebecca
Daiss,
Risk
Assessor
Reregistration
Branch
4
Health
Effects
Division
(7509C)
and
Mark
Howard/
Betty
Shackleford
Reregistration
Branch
3
Special
Review
&
Reregistration
Division
(7508C)
Action
Requested
Prepare
the
revised
anticipated
residues
and
acute,
chronic,
and
cancer
dietary
exposure
and
risk
analyses
for
lindane
(009001)
incorporating
comments
from
the
public
and
deleting
seed
treatment
uses
on
broccoli,
Brussels
sprouts,
cabbage,
cauliflower,
lettuce,
radishes,
and
spinach
which
are
no
longer
being
supported
for
reregistration
by
Inquinosa.
The
OPP/
Cancer
Assessment
Review
Committee
(CARC)
has
completed
the
reviewof
newlysubmitted
carcinogenicitystudyinCD
1
mice
2
along
with
other
data.
In
accordance
with
the
EPADraft
Guidelines
for
Carcinogen
Risk
Assessment
(July,
1999),
the
CARC
has
classified
lindane
into
the
category
"Suggestive
evidence
of
carcinogenicity,
but
not
sufficient
to
assess
human
carcinogenic
potential"
based
on
an
increased
incidence
of
benign
lung
tumors
in
female
mice
only.
The
Committee,
therefore,
recommended
that
the
quantification
of
human
cancer
risk
is
not
required.
Executive
Summary
°
Estimated
acute
dietary
exposure
is
below
HED's
level
of
concern
for
all
population
subgroups
at
the
99.9
th
percentile.
The
maximum
dietary
risk
estimate
is
17
%
of
the
acute
PAD
(%
aPAD)
for
the
population
subgroup
All
Infants
(Table
18)
and
7
%
of
the
aPAD
for
the
U.
S.
Population
when
the
feeding
studies
were
adjusted
using
the
metabolism
studies.
°
Estimated
chronic
dietary
risk
is
below
HED's
level
of
concern
for
all
population
subgroups.
The
resulting
risk
estimates
are
3
%
of
the
chronic
PAD
(%
cPAD)
for
the
U.
S.
Population
and
11
%
of
the
cPAD
for
Children
1
6
years
of
age
(highest
exposed
population
subgroup)
and
6
%
of
the
cPAD
for
Children
7
12
yrs.
The
remaining
population
subgroups
were
5
%of
the
cPAD(
Table
18)
when
the
feeding
studies
were
adjusted
using
the
ratio
of
ppm
TRR/
ppm
lindane
identified
in
the
metabolism
studies
(Table
18).
Toxicological
Information
Memoranda
providing
details
of
relevant
toxicological
information
include
the
HIARC
report
dated
7/
27/
00
and
the
FQPA
Safety
Factor
Committee
report
dated
8/
2/
00.
The
acute
and
chronic
FQPA
safety
factors
of
10X
were
reduced
to
3X
(see
FQPA
Safety
Factor
Document,
8/
2/
00).
Areference
dose
(RfD)
which
includes
the
FQPA
safety
factor
(10X,
3Xor
1X)
is
defined
as
the
Population
Adjusted
Dose
(PAD).
Doses
and
endpoints
for
dietary
risk
assessment
are
presented
in
Table
1.
The
OPP/
Cancer
Assessment
Review
Committee
(CARC)
has
completed
the
review
of
newly
submitted
carcinogenicity
study
in
CD
1
mice
along
with
other
data.
In
accordance
with
the
EPA
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(July,
1999),
the
CARC
has
classified
lindane
into
the
category
"Suggestive
evidence
of
carcinogenicity,
but
not
sufficient
to
assess
human
carcinogenic
potential"
based
on
an
increased
incidence
of
benign
lung
tumors
in
female
mice
only.
The
Committee,
therefore,
recommended
that
the
quantification
of
human
cancer
risk
is
not
required.
3
Table
1.
Lindane:
Toxicological
Doses
and
Endpoints
for
Dietary
Risk
Assessment.
EXPOSURE
SCENARIO
DOSE
(mg/
kg/
day)
ENDPOINT
STUDY
TYPE/
MRID
Acute
Dietary
general
population
NOAEL=
6
mg/
kg
UF
=
100
FQPA
=
3X
LOAELis20
mg/
kgbased
on
increasedgrip
strength,
increased
Motor
Activity
Acute
Neurotoxicity
in
Rats/
44769201
Acute
RfD
(Gen.
Pop.)
=
0.
06
mg/
kg/
day
Acute
Population
Adjusted
Dose
(aPAD)
=
0.
02
mg/
kg/
day
Chronic
Dietary
NOAEL=
10
ppm
(0.
47
mg/
kg/
day)
UF
=
100
FQPA
=
3X
LOAEL
is
100
ppm
(4.
81
mg/
kg/
day)
periacinar
hepatocyte
hypertrophy,
increased
liver/
spleen
weight,
and
increased
platelets
Chronic
Feeding
and
Carcinogenicity
in
Rats
41094101
41853701
42891201
Chronic
RfD
=
0.
0047
mg/
kg/
day
Chronic
Population
Adjusted
Dose
(cPAD)
=
0.
0016
mg/
kg/
day
Consumption
Data
HED
conducts
dietary
risk
assessments
using
the
Dietary
Exposure
Evaluation
Model
(DEEM™),
which
incorporates
consumption
data
generated
in
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(CSFII),
1989
1992.
For
acute
dietary
risk
assessments,
the
entire
distribution
of
single
day
food
consumption
events
is
combined
with
either
a
single
residue
level
(deterministic
analysis,
risk
at
95th
percentile
of
exposure
reported)
or
a
distribution
of
residues
(probabilistic
analysis,
referred
to
as
"Monte
Carlo,"
with
risk
at
99.
9th
percentile
of
exposure
reported)
to
obtain
a
distribution
of
exposures
in
mg/
kg/
day.
For
chronic
dietary
risk
assessments,
the
three
day
average
of
consumption
for
each
sub
population
is
combined
with
average
residues
in/
on
commodities
to
determine
an
average
exposure
in
mg/
kg/
day.
Residue
Information
Tolerances
for
residues
of
lindane
in/
on
food
and
feed
commodities
are
currently
established
under
40
CFR
§180.133
and
are
expressed
in
terms
of
lindane
per
se.
The
nature
of
the
residue
in
plants
and
ruminants
is
not
adequately
understood.
New
nature
of
the
residue
studies
fromseed
treatment
are
required
for
a
cereal
grain,
leafy
vegetable,
and
radish.
Additional
data
are
required
for
the
ruminant
metabolismstudy.
The
nature
ofthe
residue
in
poultry
is
adequately
understood.
The
HED
MetabolismAssessment
ReviewCommittee(T.
Morton,
8/
30/
00,
D267069)
concluded
that
theTRRs
should
be
used
for
risk
assessment
purposes
and
calculation
of
dietary
burdens,
pending
receipt
of
additional
metabolismdata.
The
anticipated
residues
(ARs)
were
presented
to
the
HED
ChemSAC
on
9/
6/
00.
Exposure
to
lindane
was
determined
by
using
the
ratio
(ppm
TRR/
ppm
lindane
parent)
fromthelivestock
metabolismstudies.
TheBiologicaland
EconomicAnalysisDivision
(OPP/
BEAD)
verified
the
registrant's
percent
market
share
estimate
for
lindane
(I.
Yusuf
email,
7/
17/
00).
The
usage
data
are
provided
as
Attachment
1;
inclusion
of
the
data
in
dietary
exposure
analyses
is
discussed
below.
Acanola
processing
studyfor
lindane
wasrecentlyreviewed
(T.
Morton,
D269388,
5/
10/
01).
Lindane
was
not
detected
in
bleached/
deodorized
canola
oil
(<
0.005
ppm).
Therefore,
½
4
LOQ
(0.0025
ppm)
will
be
used
as
the
DEEM™
adjustment
factor
1.
DEEM™
default
concentrations
factors
(adjustment
factor
1)
will
be
used
for
all
other
concentration
factors.
The
wheat
grain
and
forage
TRRs
were
translated
to
barley,
oats,
and
rye.
The
corn
grain
and
forage
TRRs
were
translated
to
sorghum.
The
following
metabolism
and
feeding
studies
were
used
to
determine
the
appropriate
residue
values
to
be
used
in
both
the
dietary
burden
calculation
and
the
DEEM™
input
files.
Seed
Treatment
Metabolism
Study
(N.
Dodd,
3/
24/
88,
RCB
3259,
MRID
40431207)
Various
seeds
were
treated
with
14
C
lindane.
Spring
wheat
seeds
were
treated
at
370
ppm
(0.
3x),
field
corn
seeds
at
1800
ppm
(0.
8x),
and
sweet
corn
seeds
at
1400
ppm
(0.
6x).
Seeds
were
then
planted
outdoors.
Samples
were
analyzed
for
radioactivity
periodically
by
oxidative
combustion
and
autoradiography.
Samples
were
extracted
and
analyzed
for
14
C
by
liquid
scintillation
counting
(LSC)
and
for
lindane
by
gas
liquid
chromatography
(GLC)
when
significant
residues
were
found
by
combustion.
This
study
was
deemed
inadequate
due
to
insufficient
characterization/
identification
of
the
radioactive
residues.
A
new
nature
of
the
residue
study
from
seed
treatment
is
required
for
a
cereal
grain.
The
HED
MARC
(T.
Morton,
8/
30/
00,
D267069)
concluded
that
the
TRRs
should
be
used
for
calculation
of
dietary
burdens.
The
TRRs
are
summarized
in
the
following
table.
Table
2.
Summary
of
TRR
in
various
crops
after
seed
treatment
with
14
C
labeled
lindane.
Crop
Matrix
TRR
(ppm)
Field
corn
root
0.
340
Field
corn
foliage
0.064
Field
corn
grain
<
0.
01
Sweet
corn
foliage
0.051
Sweet
corn
grain
<
0.01
Wheat
foliage
2.925
Wheat
grain
0.052
The
TRR
used
for
barley,
canola,
oats,
rye,
and
wheat
grain
was
0.052
ppm.
The
TRR
value
used
for
corn
grain
and
sorghum
grain
was
0.01
ppm.
Meat,
Milk,
Poultry,
&
Eggs
5
The
following
acute
dietary
burdens
(Table
3)
were
calculated
using
the
appropriate
TRRs
fromthe
seed
treatment
metabolism
study
presented
in
the
previous
table
(Table
2).
The
chronic
dietary
burdens
(Table
4)
have
incorporated
the
percent
market
share
of
the
feed
item
into
the
dietary
contribution.
Table
3.
Lindane
Acute
Dietary
Burden.
6
Feed
Commodity
%
Dry
Matter
%
Diet
Anticipated
Residue
(ppm)
Dietary
Contribution
(ppm)
Beef
Cattle
Field
corn
grain
88
50
0.01
0.0057
Wheat
forage
25
25
2.
925
2.925
Sorghum
forage
35
15
0.
064
0.028
Wheat
grain
89
10
0.052
0.006
Total
100
2.96
Dairy
Cattle
Field
corn
grain
88
40
0.01
0.0045
Wheat
grain
89
10
0.052
0.006
Wheat
forage
25
50
2.
925
5.85
Total
100
5.86
Poultry
Field
corn
grain
NA
20
0.01
0.002
Wheat
grain
NA
80
0.052
0.0416
Total
100
0.044
Swine
Field
corn
grain
NA
20
0.01
0.002
Wheat
grain
NA
80
0.052
0.0416
Total
100
0.044
Table
4.
Lindane
Chronic
Dietary
Burden.
7
Feed
Commodity
%
Dry
Matter
%
Diet
Anticipated
Residue
(ppm)
Percent
Market
Share
Dietary
Contribution
(ppm)
Beef
Cattle
Field
corn
grain
88
50
0.01
0.15
0.0009
Wheat
forage
25
25
2.
925
0.03
0.0878
Sorghum
forage
35
15
0.
064
0.03
0.0008
Wheat
grain
89
10
0.052
0.03
0.0002
Total
100
0.0897
Dairy
Cattle
Field
corn
grain
88
40
0.01
0.15
0.0007
Wheat
grain
89
10
0.052
0.03
0.0002
Wheat
forage
25
50
2.
925
0.03
0.1755
Total
100
0.1764
Poultry
Field
corn
grain
NA
20
0.01
0.15
0.0003
Wheat
grain
NA
80
0.052
0.03
0.0012
Total
100
0.0015
Swine
Field
corn
grain
NA
20
0.01
0.15
0.0003
Wheat
grain
NA
80
0.052
0.03
0.0012
Total
100
0.0015
Ruminant
Metabolism
Study
(MRID
44867104)
8
Lactating
goats
were
orally
administered
14
C
Lindane
capsules
(via
balling
gun)
immediately
after
the
morning
milking
once
per
day
for
7
days.
The
actual
dose
rat
e
was
13
mg/
kg.
This
dose
rate
is
equivalent
to
approximately
a
2x
exaggerated
rate
for
dairy
cattle
and
approximately
4.4x
for
beef
cattle
based
on
an
acute
dietary
burden
as
calculated
by
HED.
The
acute
anticipated
residues
using
the
TRR
alone
for
cattle
and
swine
are
summarized
in
Table
6
and
7.
The
chronic
anticipated
residues
usingthe
TRRalone
forcattle
andswine
aresummarizedinTable
8
and
9.
Table
5.
Summary
of
TRR
characterized/
identified
in
tissues
of
lactating
goats
orally
dosed
with
14
C
Lindane
at
13
ppm.
Tissue
Total
Radioactive
Residue
(TRR)
ppm
Fat
3.
46
ppm
Liver
2.
25
ppm
Kidney
0.
48
ppm
Muscle
0.20
ppm
Milk
Fat
0.
136
ppm
Table
6.
Cattle
Acute
Anticipated
Residues
From
Nature
of
the
residue
study
(M.
Kovacs
Jr.,
9/
20/
88,
RCB
4037).
Tissue
13
ppm
Feeding
Level
(4.
4X)
a
Cattle
AR
Fat
3.
46/
4.4=
0.786
0.786
ppm
Muscle
0.2/
4.4=
0.045
0.045
ppm
Milk
Fat
0.
136/
2=
0.068
0.068
ppm
Liver
2.
25/
4.4=
0.511
0.511
ppm
b
Kidney
0.48/
4.4=
0.109
0.109
ppm
a
The
13
ppm
feeding
level
represented
2x
the
dairy
dietary
burden.
b
Use
for
liver,
meat
byproducts,
and
other
organ
meats
for
beef,
goat,
horses,
sheep,
and
veal.
Table
7.
Swine
Acute
Anticipated
Residues
based
on
metabolism
data
from
the
ruminant
metabolism
study.
Tissue
13
ppm
Feeding
Level
(295X)
Swine
AR
Fat
3.
46/
295=
0.012
0.012
ppm
Muscle
0.2/
295=
0.001
0.001
ppm
Liver
2.
25/
295=
0.008
0.008
ppm
a
Kidney
0.48/
295=
0.002
0.002
ppm
a
Use
for
liver,
meat
byproducts,
and
other
organ
meats
for
pork.
Table
8.
Cattle
Chronic
Anticipated
Residues
From
Nature
of
the
residue
study
(M.
Kovacs
Jr.,
9/
20/
88,
RCB
4037).
9
Tissue
13
ppm
Feeding
Level
(145X)
a
Cattle
AR
Fat
3.
46/
145=
0.02
0.02
ppm
Muscle
0.2/
145=
0.001
0.001
ppm
Milk
Fat
0.
136/
74=
0.002
0.002
ppm
Liver
2.
25/
145=
0.02
0.02
ppm
b
Kidney
0.48/
145=
0.003
0.003
ppm
a
The
13
ppm
feeding
level
represented
74x
the
chronic
dairy
dietary
burden.
b
Use
for
liver,
meat
byproducts,
and
other
organ
meats
for
beef,
goat,
horses,
sheep,
and
veal.
Table
9.
Swine
Chronic
Anticipated
Residues
based
on
metabolism
data
from
the
ruminant
metabolism
study.
Tissue
13
ppm
Feeding
Level
(8700X)
Swine
AR
Fat
3.
46/
8700=
0.0004
0.0004
ppm
Muscle
0.2/
8700=
0.00002
0.00002
ppm
Liver
2.
25/
8700=
0.0003
0.0003
ppm
a
Kidney
0.48/
8700=
0.00006
0.00006
ppm
a
Use
for
liver,
meat
byproducts,
and
other
organ
meats
for
pork.
Poultry
Metabolism
Study
(MRID
40271301)
Following
4
days
of
dosing
with
[
14
C]
lindane
at
levels
equivalent
to
120
(2700x)
ppm
in
the
acute
diet,
14
C
residues
accumulated
to
the
greatest
extent
in
fatty
tissues.
In
the
high
dose
hens,
TRRs
were
highest
in
fat
(96.98
ppm)
followed
by
skin
(49.93
ppm),
thigh
muscle
(11.81
ppm),
liver
(11.65
ppm),
and
breast
muscle
(1.44
ppm).
14
C
Residues
were
readily
extracted
(80
141%
TRR)
fromyolks,
thigh
muscle,
liver,
skin,
and
fat
of
high
dose
hens
using
organic
solvents,
and
66.4
121.3%
of
the
TRR
was
subsequently
identified.
Lindane
was
the
principal
14
C
residue
identified
in
eggs
and
tissues,
accounting
for
94.5%
of
the
TRR
in
egg
yolks,
70.8
86.0%
of
the
TRR
in
muscle,
skin,
and
fat,
and
51.5%
of
the
TRR
in
liver.
1,
2,
4Trichlorobenzene
was
identified
as
accounting
for
19.4%
of
the
TRR
in
liver,
and
0.6
3.5%
of
the
TRR
in
egg
yolks
and
other
tissues.
1,
3,
5
Trichlorobenzene
and
dichlorobenzene(
s)
were
also
detected
in
liver
at
6.4
and
9.5%
of
the
TRR,
respectively.
Tetrachlorobenzene
(either
1,2,4,5
or
1,2,3,4)
was
detected
in
thigh
muscle
at
17.7%
of
the
TRR
and
in
other
tissues
at
2.2
3.1%
of
the
TRR.
Pentachlorocyclohexene
was
identified
as
accounting
for
3.
8
6.
1%
of
the
TRR
in
yolks
and
tissues.
The
remaining
metabolites
(1,
2,
3,
4
tetrachlorobenzene/
tetrachlorocyclohexene;
1,2,3,4,5
pentachlorobenzene;
and
hexachlorocyclohexene)
detected
intissues
and/
or
yolks
each
accounted
for
4.4%
of
the
TRR.
The
acute
anticipated
residues
using
the
TRR
alone
for
poultry
are
summarized
in
Table
10.
The
chronic
anticipated
residues
using
the
TRR
alone
for
poultry
are
summarized
in
Table
11.
10
Table
10.
Summary
of
TRR
characterized/
identified
in
tissues
of
laying
hens
orally
dosed
with
14
C
Lindane
at
120
ppm
(2700x
acute
dietary
burden)
normalized
to
1x
the
acute
dietary
burden.
Tissue
Total
Radioactive
Residue
(TRR)
ppm
Acute
Anticipated
Residue
(ppm)
Fat
97.0
ppm/
2700=
0.04
0.04
Liver
11.7
ppm/
2700=
0.004
0.004
Skin
49.9
ppm/
2700=
0.02
0.02*
Thigh
11.8
ppm/
2700=
0.004
0.004
Egg
White
0.21/
2700=
0.00008
0.00008
Egg
Yolk
10.8
ppm/
2700=
0.004
0.004
Whole
Egg
0.7(
0.00008)+
0.
3(
0.
004)=
0.
001
*Use
for
poultry
meat
byproducts
Table
11.
Summary
of
TRR
characterized/
identified
in
tissues
of
laying
hens
orally
dosed
with
14
C
Lindane
at
120
ppm
(80000x
acute
dietary
burden)
normalized
to
1x
the
chronic
dietary
burden.
Tissue
Total
Radioactive
Residue
(TRR)
ppm
Chronic
Anticipated
Residue
(ppm)
Fat
97.0
ppm/
80000=
0.001
0.001
Liver
11.7
ppm/
80000=
0.0001
0.0001
Skin
49.9
ppm/
80000=
0.0006
0.0006*
Thigh
11.8
ppm/
80000=
0.0001
0.0001
Egg
White
0.21/
80000=
0.000003
0.000003
Egg
Yolk
10.8
ppm/
80000
0.0001
Whole
Egg
0.7(
0.000003)+
0.
3(
0.
0001)=
0.
00003
*Use
for
poultry
meat
byproducts
Ruminant
Feeding
Study
(M.
Kovacs
Jr.,
9/
20/
88,
RCB
4037)
Dairy
cattle
were
fed
at
three
feeding
levels
of
20
ppm(
6.
7x
acute
beef
cattle
dietary
burden),
60
ppm
(20x
acute
beef
cattle
dietary
burden),
and
200
ppm
(67x
acute
beef
cattle
dietary
burden).
The
exaggerated
feeding
rates
correspond
to
3.
4x,
10x,
and
34x
for
the
acute
dairy
cattle
dietary
burden,
respectively.
The
exaggerated
feeding
rates
correspond
to
450x,
1400x,
and
4500x
for
the
acute
swine
dietary
burden,
respectively.
The
acute
anticipated
residues
for
cattle
and
swine
using
the
feeding
studies
along
with
information
fromthe
metabolismstudies
are
summarized
in
Tables
12
and
13.
The
chronic
anticipated
residues
for
cattle
and
swine
using
the
feeding
studies
along
with
information
from
the
metabolism
studies
are
summarized
in
Tables
14
and
15.
Table
12.
Summary
of
lindane
residues
in
cattle
fed
at
20,
60,
and
200
ppm
normalized
to
a
1x
acute
feeding
level.
11
Sample
20
ppm
(6.7x)
a
60
ppm
(20x)
a
200
ppm
(67x)
a
Average
(ppm)
*
(ppm
TRR/
ppm
lindane)
b
Milk
(Day
7)
0.41/
3.4
=
0.120
1.64/
10
=
0.
164
3.95/
34
=
0.
116
0.133
*
1.
22
=
0.163
Liver
0.
10/
6.7
=
0.015
0.19/
20
=
0.
009
0.72/
67
=
0.
011
0.012
*
6.
25
=
0.073
Kidney
0.34/
6.7
=
0.051
1.07/
20
=
0.
053
4.57/
67
=
0.
068
0.057
*
2.
82
=
0.162
Muscle
0.97/
6.7
=
0.145
1.80/
20
=
0.
090
8.75/
67
=
0.
130
0.122
*
1.
25
=
0.152
Fat
11.9/
6.7
=
1.78
20.2/
20
=
1.
01
58.1/
67
=
0.
87
1.
22
*
1.
18
=
1.44
a
First
number
in
column
is
residue
value
from
feeding
study
which
is
then
divided
by
the
exaggerated
feeding
rate.
b
Average
residue
value
from
three
feeding
levels
multiplied
by
the
ratio
of
(ppm
TRR/
ppm
lindane)
in
metabolism
study.
Table
13.
Summary
of
lindane
residues
in
swine
translated
from
the
cattle
feeding
study
and
normalized
to
1x
acute
feeding
level.
Sample
20
ppm
(450x)
a
60
ppm
(1400x)
a
200
ppm
(4500x)
a
Average
(ppm)
*
(ppm
TRR/
ppm
lindane)
b
Liver
0.
10/
450=
0.0002
0.19/
1400=
0.0001
0.72/
4500=
0.0002
0.0002
*
6.
25
=
0.001
Kidney
0.34/
450=
0.0007
1.07/
1400=
0.0008
4.57/
4500=
0.001
0.0008
*
2.
82
=
0.002
Muscle
0.97/
450=
0.002
1.80/
1400=
0.001
8.75/
4500=
0.002
0.002
*
1.
25
=
0.002
Fat
11.9/
450=
0.026
20.2/
1400=
0.014
58.1/
4500=
0.013
0.018
*
1.
18
=
0.021
a
First
number
in
column
is
residue
value
from
feeding
study
which
is
then
divided
by
the
exaggerated
feeding
rate.
b
Average
residue
value
from
three
feeding
levels
multiplied
by
the
ratio
of
(ppm
TRR/
ppm
lindane)
in
metabolism
study.
Table
14.
Summary
of
lindane
residues
in
cattle
fed
at
20,
60,
and
200
ppm
normalized
to
a
1x
chronic
feeding
level.
Sample
20
ppm
(223x)
a
60
ppm
(669x)
a
200ppm(
2230x)
a
Average
(ppm)
*
(ppm
TRR/
ppm
lindane)
b
Milk
(Day
7)
0.41/
113=
0.004
1.64/
340=
0.005
3.95/
1134=
0.003
0.004
*
1.
22
=
0.005
Liver
0.
10/
223=
0.0004
0.19/
669=
0.0003
0.72/
2230=
0.0003
0.0003
*
6.
25
=
0.002
Kidney
0.
34/
223=
0.002
1.07/
669=
0.002
4.57/
2230=
0.002
0.002
*
2.
82
=
0.006
Muscle
0.97/
223=
0.004
1.80/
669=
0.003
8.75/
2230=
0.004
0.004
*
1.
25
=
0.005
Fat
11.9/
223=
0.05
20.2/
669=
0.03
58.1/
2230=
0.03
0.04
*
1.
18
=
0.05
a
First
number
in
column
is
residue
value
from
feeding
study
which
is
then
divided
by
the
exaggerated
feeding
rate.
b
Average
residue
value
from
three
feeding
levels
multiplied
by
the
ratio
of
(ppm
TRR/
ppm
lindane)
in
metabolism
study.
Table
15.
Summary
of
lindane
residues
in
swine
translated
fromthe
cattle
feeding
study
and
normalized
to
1x
chronic
12
feeding
level.
Sample
20
ppm
(13300x)
a
60
ppm
(40000x)
a
200
ppm
(133000x)
a
Average
(ppm)
*
(ppm
TRR/
ppm
lindane)
b
Liver
0.
10/
13300=
0.000
008
0.19/
40000=
0.0000
05
0.72/
133000=
0.000005
0.000006
*
6.
25
=
0.00004
Kidney
0.34/
13300=
0.000
03
1.07/
40000=
0.0000
3
4.57/
133000=
0.00003
0.00003
*
2.
82
=
0.00008
Muscle
0.97/
13300=
0.000
07
1.80/
40000=
0.0000
5
8.75/
133000=
0.00007
0.00006
*
1.
25
=
0.00008
Fat
11.9/
13300=
0.000
9
20.2/
40000=
0.0005
58.1/
133000=
0.0004
0.0006
*
1.
18
=
0.0007
a
First
number
in
column
is
residue
value
from
feeding
study
which
is
then
divided
by
the
exaggerated
feeding
rate.
b
Average
residue
value
from
three
feeding
levels
multiplied
by
the
ratio
of
(ppm
TRR/
ppm
lindane)
in
metabolism
study.
Poultry
Feeding
Study
(G.
Otakie,
8/
31/
88,
RCB
4034)
Poultry
were
fed
lindane
at
1.5
(34x
the
acute
dietary
burden),
4.
5
(102x
the
acute
dietary
burden),
and
15
(340x
the
acute
dietary
burden)
ppmfeeding
levels.
The
acute
anticipated
residues
for
poultry
using
the
feeding
study
along
with
information
from
the
metabolism
study
are
summarized
in
Table
16.
The
chronic
anticipated
residues
for
poultry
using
the
feeding
study
along
with
information
from
the
metabolism
study
are
summarized
in
Table
17.
Table
16.
Summary
of
lindane
residues
in
poultry
fed
at
1.5,
4.5,
and
15
ppm
normalized
to
a
1x
acute
feeding
level.
Sample
1.5
ppm
(34x)
a
4.5
ppm
(102x)
a
15
ppm
(340x)
a
Average
(ppm)
*
(ppm
TRR/
ppm
lindane)
b
Eggs
0.216/
34
=
0.
006
0.672/
102
=
0.
006
2.357/
340
=
0.
007
0.006
*
1.
06
=
0.006
Liver
0.
12/
34
=
0.
003
0.51/
102
=
0.
005
0.78/
340
=
0.
002
0.003
*
1.
95
=
0.006
Heart
0.
33/
34=
0.
010
0.
89/
102=
0.
009
2.
26/
340=
0.
007
0.
009
*1
=0.
009
c
Thigh
0.
19/
34
=
0.
005
0.36/
102
=
0.
003
1.35/
340
=
0.
004
0.004
*
1.
40
=
0.006
Fat
2.
54/
34
=
0.
075
7.8/
102
=
0.
076
27.7/
340
=
0.
081
0.077
*
1.
17
=
0.090
a
First
number
in
column
is
residue
value
from
feeding
study
which
is
then
divided
by
the
exaggerated
feeding
rate.
b
Average
residue
value
from
three
feeding
levels
multiplied
by
the
ratio
of
(ppm
TRR/
ppm
lindane)
in
metabolism
study.
c
100%
of
the
TRR
in
the
chicken
heart
was
identified
as
lindane.
This
residue
was
used
for
chicken
byproducts,
chicken
giblets
(excl.
liver),
turkey
byproducts,
turkey
other
organ
meats,
and
turkey
giblets
(excl.
liver).
Table
17.
Summaryof
lindane
residues
in
poultry
fed
at
1.5,
4.5,
and
15
ppm
normalized
to
a
1x
chronic
feeding
level.
13
Sample
1.5
ppm
(1000x)
a
4.5
ppm
(3000x)
a
15
ppm
(10000x)
a
Average
(ppm)
*
(ppm
TRR/
ppm
lindane)
b
Eggs
0.216/
1000=
0.0002
0.672/
3000=
0.0002
2.357/
10000=
0.0002
0.002
*
1.
06
=
0.0002
Liver
0.
12/
1000=
0.0001
0.51/
3000=
0.0002
0.78/
10000=
0.00008
0.0001
*
1.
95
=
0.0002
Heart
0.
33/
1000=
0.0003
0.89/
3000=
0.0003
2.26/
10000=
0.0002
0.0003
*1
=0.
0003
c
Thigh
0.
19/
1000=
0.0002
0.36/
3000=
0.0001
1.35/
10000=
0.0001
0.0001
*
1.
40
=
0.0002
Fat
2.
54/
1000=
0.003
7.8/
3000=
0.003
27.7/
10000=
0.003
0.003
*
1.
17
=
0.004
a
First
number
in
column
is
residue
value
from
feeding
study
which
is
then
divided
by
the
exaggerated
feeding
rate.
b
Average
residue
value
from
three
feeding
levels
multiplied
by
the
ratio
of
(ppm
TRR/
ppm
lindane)
in
metabolism
study.
c
100%
of
the
TRR
in
the
chicken
heart
was
identified
as
lindane.
This
residue
was
used
for
chicken
byproducts,
chicken
giblets
(excl.
liver),
turkey
byproducts,
turkey
other
organ
meats,
and
turkey
giblets
(excl.
liver).
Uncertainties
There
are
no
adequate
nature
of
the
residue
studies
for
plants
fromseed
treatment
application.
Anew
metabolism
study
is
required
for
a
grain
crop;
however,
a
seed
treatment
metabolism
study
(which
was
classified
as
inadequate)
was
reviewed
by
HED
and
used
in
the
determination
of
the
TRR
for
use
in
this
dietary
exposure
analysis.
The
wheat
grain
and
forage
TRRs
were
translated
to
barley,
oats,
and
rye.
The
corn
grain
and
forage
TRRs
were
translated
to
sorghum.
The
nature
of
the
residue
in
poultry
is
understood.
The
nature
of
the
residue
in
livestock
is
adequately
understood.
The
magnitude
of
the
residue
studies
in
poultry
and
cattle
only
analyzed
for
lindane.
The
lindane
residue
values
were
derived
using
a
ratio
of
total
radioactive
residue
divided
by
the
amount
of
lindane
present
in
the
livestock
metabolism
studies.
This
would
be
worst
case
estimate
since
we
are
assuming
that
all
of
the
TRR
would
be
residues
of
concern
and
adjusting
the
lindane
residues
in
the
livestock
magnitude
of
the
residue
studies
accordingly
to
account
for
the
TRR.
The
dietaryexposure
analyses
using
the
total
radioactive
residues
is
a
Tier
3
assessment
since
percent
crop
treated
was
used
in
the
analyses.
The
dietary
exposure
analyses
that
were
based
on
the
adjustment
of
the
lindane
residues
in
the
feeding
studies
is
a
Tier
3
assessment.
Percent
market
share
was
available
for
all
crops
included
in
the
analyses.
Since
lindane
is
being
supported
for
reregistration
for
seed
treatments
only,
there
is
no
difference
in
the
percent
crop
treated
values
between
crops
grown
for
the
fresh
market
and
those
grown
for
processing.
A
processing
study
was
available
for
canola
only;
the
default
DEEM™
processing
factors
were
used
for
all
other
foods.
Results/
Discussion
14
Estimated
acute
dietary
exposure
is
below
HED's
level
of
concern
for
all
population
subgroups
at
the
99.9
th
percentile.
The
maximum
dietary
risk
estimate
is
17
%
of
the
aPAD
for
All
Infants
when
the
feeding
studies
were
adjusted
using
the
metabolism
studies
(Table
18).
Estimated
chronic
dietary
risk
is
below
HED's
level
of
concern
for
all
population
subgroups.
The
resulting
risk
estimates
are
3
%
of
the
chronic
PAD
(%
cPAD)
for
the
U.
S.
Population
and
11
%
of
the
cPADfor
Children
1
6
years
of
age
(highest
exposed
population
subgroup)
and
6
%of
the
cPAD
for
Children
7
12
yrs.
The
remaining
population
subgroups
were
5%
ofthe
cPAD
(Table
18)
when
the
feeding
studies
were
adjusted
using
the
ratio
of
ppm
TRR/
ppm
lindane
identified
in
the
metabolism
studies
(Table
18).
Table
18.
Estimated
Acute
and
Chronic
Dietary
Exposure
and
Risk
using
the
feeding
studies
and
adjusting
lindane
residues
using
the
metabolism
studies.
Population
Subgroup
Acute
(99.9th
%
ile)
Chronic
Exposure
(mg/
kg/
day)
%aPAD
Exposure
(mg/
kg/
day)
%
cPAD
U.
S.
Population
0.
001305
7
0.
000054
3
All
infants
(<
1
yr)
0.003320
17
0.000072
5
Children
(1
6
yrs)
0.
001973
10
0.000173
11
Children
(7
12
yrs)
0.001088
5
0.
000096
6
Females
(13
50
yrs)
0.000467
2
0.
000034
2
Males
(13
19
yrs)
0.000670
3
0.
000061
4
Males
(20+
yrs)
0.000458
2
0.
000034
2
Seniors
(55+
yrs)
0.000409
2
0.
000030
2
cc
:
Chem
F,
Chron
F.
Morton
,
L.
Richardson
RDI:
Chemistry
SAC
(9/
6/
00);
DE
SAC
(9/
25/
00)
(S.
Piper,
12/
13/
01
&
D.
Soderberg,
12/
13/
01);
SVH:
12/
13/
01
TM,
Thurston
Morton,
Rm.
816D
CM2,
305
6691,
mail
code
7509C
List
of
Attachments:
Attachment
1:
Quantitative
Usage
Analysis,
7/
17/
00
(I.
Yusuf,
BEAD/
OPP).
Attachment
2:
Residue
Distribution
Files.
Attachment
3:
Residue
Information.
Attachment
4:
Acute
Analysis.
Attachment
5:
Chronic
Analysis.
Attachment
1:
Quantitative
Usage
Analysis,
7/
17/
00
(I.
Yusuf,
BEAD/
OPP).
(Registrant
submission
approved
by
BEAD)
15
From
the
Small
Grains
petition,
Page
79.
B.
Market
share
representing
maximum
percent
of
crop
treated
is
15%
for
field
corn,
10%
for
canola,
1%
for
sweet
corn,
and
3%
each
for
wheat,
oats,
barley,
and
grain
sorghum.
From
the
Small
Grains
petition,
Page
35
MARKET
SHARE
Reasonable
estimates
for
the
percentage
of
seeds
of
wheat,
barley,
oats,
rye,
and
sorghum
treated
with
lindane
i.
e.,
the
market
share,
are
1%
to
3%.
The
market
share
on
corn
may
be
as
high
as
15%.
Market
share
information
was
used
in
calculations
of
Maximum
Theoretical
Dietary
Burdens
for
livestock,
and
was
considered
in
some
estimations
of
human
dietary
exposure.
From
the
vegetables
petition,
Page
22.
MARKET
SHARE:
Reasonable
estimates
for
the
percentage
of
acres
employing
lindane
treated
seeds
are:
corn
15%,
brassica
<
1%,
leafy
vegetables
<
1%,
and
radishes
<
1%.
(Personal
Communication:
T.
McArtle,
Trace
Chemical
and
Seed
Treatment
Coalition
representative,
December
1998).
Attachment
2:
RDFs
Documentation:
doc
beef
fat
lindane
DOC
ASSUMING
15%
crop
treated
for
highest
feed
item
TOTALZ=
85
16
TOTALFREQ=
1
15,1.44
Documentation:
doc
beef
meat
lindane
DOC
ASSUMING
15%
crop
treated
for
highest
feed
item
TOTALZ=
85
TOTALFREQ=
1
15,0.152
Documentation:
doc
beef
meat
by
products
lindane
DOC
ASSUMING
15%
crop
treated
for
highest
feed
item
TOTALZ=
85
TOTALFREQ=
1
15,0.162
Documentation:
doc
beef
liver
lindane
DOC
ASSUMING
15%
crop
treated
for
highest
feed
item
TOTALZ=
85
TOTALFREQ=
1
15,0.073
Documentation:
doc
milk
lindane
DOC
ASSUMING
15%
crop
treated
for
highest
feed
item
TOTALZ=
85
TOTALFREQ=
1
15,0.163
Documentation:
doc
poultry
eggs
lindane
DOC
ASSUMING
15%
crop
treated
for
highest
feed
item
TOTALZ=
85
TOTALFREQ=
1
15,0.006
Documentation:
doc
poultry
meat
byproducts
lindane
DOC
ASSUMING
15%
crop
treated
for
highest
feed
item
TOTALZ=
85
TOTALFREQ=
1
15,0.009
Documentation:
doc
poultry
liver
lindane
DOC
ASSUMING
15%
crop
treated
for
highest
feed
item
TOTALZ=
85
TOTALFREQ=
1
15,0.006
17
Documentation:
doc
poultry
giblets
lindane
DOC
ASSUMING
15%
crop
treated
for
highest
feed
item
TOTALZ=
85
TOTALFREQ=
1
15,0.009
Documentation:
doc
poultry
fat
lindane
DOC
ASSUMING
15%
crop
treated
for
highest
feed
item
TOTALZ=
85
TOTALFREQ=
1
15,0.09
Documentation:
doc
poultry
meat
lindane
DOC
ASSUMING
15%
crop
treated
for
highest
feed
item
TOTALZ=
85
TOTALFREQ=
1
15,0.006
Documentation:
doc
swine
fat
lindane
DOC
ASSUMING
15%
crop
treated
for
highest
feed
item
TOTALZ=
85
TOTALFREQ=
1
15,0.021
Documentation:
doc
swine
meat
byproducts
lindane
DOC
ASSUMING
15%
crop
treated
for
highest
feed
item
TOTALZ=
85
TOTALFREQ=
1
15,0.002
Documentation:
doc
swine
liver
lindane
DOC
ASSUMING
15%
crop
treated
for
highest
feed
item
TOTALZ=
85
TOTALFREQ=
1
15,0.001
Documentation:
doc
swine
meat
lindane
DOC
ASSUMING
15%
crop
treated
for
highest
feed
item
TOTALZ=
85
TOTALFREQ=
1
15,0.002
Attachment
3:
Residue
Information
Acute
Analysis
using
feeding
study
18
F
i
l
e
n
a
m
e
:
C
:\d
e
e
m
\
9
1\R
e
v
i
s
e
d
Analysis\
12
11
1\
12
11
1RevacuteTRR.
RS7
Chemical:
Lindane
R
D(
Chronic): .
16
mg/
kg
bw/
day
NOEL(
Chronic): .
47
mg/
kg
bw/
day
R
D(
Acute): .
2
mg/
kg
bw/
day
NOEL(
Acute):
6
mg/
kg
bw/
day
Q*=
1.
1
Date
created/
last
modi
ied:
12
3
2
1/
5:
14:
17/
8
Program
ver.
7.
75
Comment:
Re
erence
doses
have
3X
FQPA
actored
in.
This
is
a
dietary
analysis
using
the
total
radioactive
residues
rom
the
plant
and
animal
metabolism
studies.
RDL
indices
and
parameters
or
Monte
Carlo
Analysis:
Index
Dist
Parameter #
1
Param #
2
Param #
3
#
Code
1
6
bee
meat.
rd
2
6
bee
at.
rd
3
6
bee
liver.
rd
4
6
bee
mbyp.
rd
5
6
poultryegg.
rd
6
6
poultry
at.
rd
7
6
poultrygiblets.
rd
8
6
poultryliver.
rd
9
6
poultrymbyp.
rd
1
6
poultrymeat.
rd
11
6
swine
at.
rd
12
6
swineliver.
rd
13
6
swinembyp.
rd
14
6
swinemeat.
rd
15
6
milk.
rd
Food
Crop
Food
Name
De
Res
Adj.
Factors
RDL
Code
Grp (
ppm) #
1 #
2
Pntr
265
15
Barley
.
52
1.
.
3
323
M
Bee
dried
.
45
1.
92
.15
1
19
324
M
Bee
at
w/
o
bones
.786
1.
.15
2
325
M
Bee
kidney
.1
9
1.
.15
4
327
M
Bee
lean (
at/
ree)
w/
o
bones
.
45
1.
.15
1
326
M
Bee
liver
.511
1.
.15
3
321
M
Bee
meat
byproducts
.511
1.
.15
4
322
M
Bee
other
organ
meats
.511
1.
.15
4
3
1
O
Canola
oil (
rape
seed
oil)
.
25
1.
.1
366
P
Chicken
byproducts
.
4
1.
.15
9
368
P
Chicken
at
w/
o
bones
.
4
1.
.15
6
367
P
Chicken
giblets(
liver)
.
4
1.
.15
8
385
P
Chicken
giblets (
excl.
liver)
.
4
1.
.15
7
369
P
Chicken
lean/
at
ree
w/
o
bones
.
4
1.
.15
1
267
15
Corn
grain
bran
.
1
1.
.15
266
15
Corn
grain
endosperm
.
1
1.
.15
289
15
Corn
grain
oil
.
1
1.
.15
268
15
Corn
grain/
sugar/
h
cs
.
1
1.
5
.15
388
15
Corn
grain/
sugar
molasses
.
1
1.
5
.15
237
15
Corn/
pop
.
1
1.
.15
238
15
Corn/
sweet
.
1
1.
.
1
364
P
Eggs
white
only
.
8
1.
.15
5
363
P
Eggs
whole
.
1
1.
.15
5
20
365
P
Eggs
yolk
only
.
4
1.
.15
5
33
M
Goat
at
w/
o
bone
.786
1.
.15
2
331
M
Goat
kidney
.1
9
1.
.15
4
333
M
Goat
lean (
at/
ree)
w/
o
bone
.
45
1.
.15
1
332
M
Goat
liver
.511
1.
.15
3
328
M
Goat
meat
byproducts
.511
1.
.15
4
329
M
Goat
other
organ
meats
.511
1.
.15
4
334
M
Horsemeat
.
45
1.
.15
1
398
D
Milk
based
water
.
68
1.
.15
15
319
D
Milk
at
solids
.
68
1.
.15
15
318
D
Milk
non
at
solids
.
68
1.
.15
15
32
D
Milk
sugar (
lactose)
.
68
1.
.15
15
399
15
Oats
bran
.
52
1.
.
3
269
15
Oats
.
52
1.
.
3
344
M
Pork
at
w/
o
bone
.
12
1.
.15
11
345
M
Pork
kidney
.
2
1.
.15
13
347
M
Pork
lean (
at
ree)
w/
o
bone
.
1
1.
.15
14
346
M
Pork
liver
.
8
1.
.15
12
342
M
Pork
meat
byproducts
.
8
1.
.15
13
343
M
Pork
other
organ
meats
.
8
1.
.15
13
362
P
Poultry
other
at
w/
o
bones
.
4
1.
.15
6
21
361
P
Poultry
other
giblets(
liver)
.
4
1.
.15
8
36
P
Poultry
other
lean
(
at
ree)
w/
.
4
1.
.15
1
274
15
Rye
lour
.
52
1.
.
3
273
15
Rye
germ
.
52
1.
.
3
272
15
Rye
rough
.
52
1.
.
3
338
M
Sheep
at
w/
o
bone
.786
1.
.15
2
339
M
Sheep
kidney
.1
9
1.
.15
4
341
M
Sheep
lean (
at
ree)
w/
o
bone
.
45
1.
.15
1
34
M
Sheep
liver
.511
1.
.15
3
336
M
Sheep
meat
byproducts
.511
1.
.15
4
337
M
Sheep
other
organ
meats
.511
1.
.15
4
275
15
Sorghum (
including
milo)
.
1
1.
.
3
355
P
Turkey
byproducts
.
4
1.
.15
9
357
P
Turkey
at
w/
o
bones
.
4
1.
.15
6
356
P
Turkey
giblets (
liver)
.
4
1.
.15
8
358
P
Turkey
lean/
at
ree
w/
o
bones
.
4
1.
.15
1
449
P
Turkey
other
organ
meats
.
4
1.
.15
9
429
M
Veal
dried
.
45
1.
92
.15
1
424
M
Veal
at
w/
o
bones
.786
1.
.15
2
426
M
Veal
kidney
.1
9
1.
.15
4
425
M
Veal
lean (
at
ree)
w/
o
bones
.
45
1.
.15
1
22
427
M
Veal
liver
.511
1.
.15
3
43
M
Veal
meat
byproducts
.511
1.
.15
4
428
M
Veal
other
organ
meats
.511
1.
.15
4
278
15
Wheat
bran
.
52
1.
.
3
279
15
Wheat
lour
.
52
1.
.
3
277
15
Wheat
germ
.
52
1.
.
3
437
15
Wheat
germ
oil
.
52
1.
.
3
276
15
Wheat
rough
.
52
1.
.
3
Chronic
Analysis
using
feeding
study
F
i
l
e
n
am
e
:
C
:\d
e
e
m
\
9
1
\R
e
v
i
s
e
d
Analysis\
12
11
1\
12
11
1RevchronicTRR.
RS7
Chemical:
Lindane
R
D(
Chronic): .
16
mg/
kg
bw/
day
NOEL(
Chronic): .
47
mg/
kg
bw/
day
R
D(
Acute): .
2
mg/
kg
bw/
day
NOEL(
Acute):
6
mg/
kg
bw/
day
Q*=
1.
1
Date
created/
last
modi
ied:
12
3
2
1/
5:
15:
47/
8
Program
ver.
7.
75
Comment:
Fe
erence
doses
have
3X
FQPA
actored
in.
This
is
the
dietary
analysis
using
the
metabolism
and
eeding
studies.
Food
Crop
De
Res
Adj.
Factors
Code
Grp
Food
Name (
ppm) #
1 #
2
265
15
Barley
.
52
1.
.
3
323
M
Bee
dried
.
5
1.
92
1.
324
M
Bee
at
w/
o
bones
.
5
1.
1.
325
M
Bee
kidney
.
6
1.
23
1.
327
M
Bee
lean (
at/
ree)
w/
o
bones
.
5
1.
1.
326
M
Bee
liver
.
2
1.
1.
321
M
Bee
meat
byproducts
.
6
1.
1.
322
M
Bee
other
organ
meats
.
6
1.
1.
3
1
O
Canola
oil (
rape
seed
oil)
.
25
1.
.1
366
P
Chicken
byproducts
.
3
1.
1.
368
P
Chicken
at
w/
o
bones
.
4
1.
1.
367
P
Chicken
giblets(
liver)
.
2
1.
1.
385
P
Chicken
giblets (
excl.
liver)
.
3
1.
1.
369
P
Chicken
lean/
at
ree
w/
o
bones
.
2
1.
1.
267
15
Corn
grain
bran
.
1
1.
.15
266
15
Corn
grain
endosperm
.
1
1.
.15
289
15
Corn
grain
oil
.
1
1.
.15
268
15
Corn
grain/
sugar/
h
cs
.
1
1.
5
.15
388
15
Corn
grain/
sugar
molasses
.
1
1.
5
.15
237
15
Corn/
pop
.
1
1.
.15
238
15
Corn/
sweet
.
1
1.
.
1
364
P
Eggs
white
only
.
2
1.
1.
363
P
Eggs
whole
.
2
1.
1.
365
P
Eggs
yolk
only
.
2
1.
1.
33
M
Goat
at
w/
o
bone
.
5
1.
24
1.
331
M
Goat
kidney
.
6
1.
1.
333
M
Goat
lean (
at/
ree)
w/
o
bone
.
5
1.
1.
332
M
Goat
liver
.
2
1.
1.
328
M
Goat
meat
byproducts
.
6
1.
1.
329
M
Goat
other
organ
meats
.
6
1.
1.
334
M
Horsemeat
.
5
1.
1.
398
D
Milk
based
water
.
5
1.
1.
319
D
Milk
at
solids
.
5
1.
1.
318
D
Milk
non
at
solids
.
5
1.
1.
32
D
Milk
sugar (
lactose)
.
5
1.
1.
399
15
Oats
bran
.
52
1.
.
3
269
15
Oats
.
52
1.
.
3
344
M
Pork
at
w/
o
bone
.
7
1.
1.
345
M
Pork
kidney
.
8
1.
1.
347
M
Pork
lean (
at
ree)
w/
o
bone
.
8
1.
1.
346
M
Pork
liver
.
4
1.
1.
342
M
Pork
meat
byproducts
.
8
1.
1.
343
M
Pork
other
organ
meats
.
8
1.
1.
362
P
Poultry
other
at
w/
o
bones
.
4
1.
1.
361
P
Poultry
other
giblets(
liver)
.
2
1.
1.
36
P
Poultry
other
lean
(
at
ree)
w/
.
2
1.
25
1.
274
15
Rye
lour
.
52
1.
.
3
273
15
Rye
germ
.
52
1.
.
3
272
15
Rye
rough
.
52
1.
.
3
338
M
Sheep
at
w/
o
bone
.
5
1.
1.
339
M
Sheep
kidney
.
6
1.
1.
341
M
Sheep
lean (
at
ree)
w/
o
bone
.
5
1.
1.
34
M
Sheep
liver
.
2
1.
1.
336
M
Sheep
meat
byproducts
.
6
1.
1.
337
M
Sheep
other
organ
meats
.
6
1.
1.
275
15
Sorghum (
including
milo)
.
1
1.
.
3
355
P
Turkey
byproducts
.
3
1.
1.
357
P
Turkey
at
w/
o
bones
.
4
1.
1.
356
P
Turkey
giblets (
liver)
.
2
1.
1.
358
P
Turkey
lean/
at
ree
w/
o
bones
.
2
1.
1.
449
P
Turkey
other
organ
meats
.
3
1.
1.
429
M
Veal
dried
.
5
1.
92
1.
424
M
Veal
at
w/
o
bones
.
5
1.
1.
426
M
Veal
kidney
.
6
1.
1.
425
M
Veal
lean (
at
ree)
w/
o
bones
.
5
1.
1.
427
M
Veal
liver
.
2
1.
1.
43
M
Veal
meat
byproducts
.
6
1.
26
1.
428
M
Veal
other
organ
meats
.
6
1.
1.
278
15
Wheat
bran
.
52
1.
.
3
279
15
Wheat
lour
.
52
1.
.
3
277
15
Wheat
germ
.
52
1.
.
3
437
15
Wheat
germ
oil
.
52
1.
.
3
276
15
Wheat
rough
.
52
1.
.
3
Attachment
4:
Acute
Analysis
Acute
Analysis
Using
Feeding
Studies
U.
S.
Environmental
Protection
Agency
Ver.
7.
74
DEEM
ACUTE
Analysis
or
LINDANE
(1989
92
data)
Residue
ile:
12
11
1RevacuteTRR.
RS7
Adjustment
actor #
2
used.
Analysis
Date:
12
11
2
1/
16:
9:
Residue
ile
dated:
12
3
2
1/
5:
14:
17/
8
NOEL (
Acute) =
6.
mg/
kg
body
wt/
day
Daily
totals
or
ood
and
ood
orm
consumption
used.
MC
iterations =
5
MC
list
in
residue
ile
MC
seed =
1
281
Run
Comment: "
Re
erence
doses
have
3X
FQPA
actored
in.
This
is
a
dietary
ana
lysis
using
the
total
radioactive
residues
rom
the
plant
and
animal
metabolism
studies."
=================================================================
==============
Summary
calculations (
per
capita):
27
95th
Percentile
99th
Percentile
99.
9th
Percentile
Exposure %
aR
D
MOE
Exposure %
aR
D
MOE
Exposure
%
aR
D
MOE
U.
S.
Population:
.
16
.8
37614
.
516
2.
58
11627
.
13
5
6.
52
4598
U.
S.
Population (
spring
season):
.
16
.8
3739
.
5
3
2.
51
11934
.
129
6.
45
465
U.
S.
Population (
summer
season):
.
152
.76
39455
.
521
2.
6
11525
.
1434
7.
17
4185
U.
S.
Population (
autumn
season):
.
166
.83
36
52
.
563
2.
82
1
648
.
1294
6.
47
4636
U.
S.
Population (
winter
season):
.
161
.8
37353
.
478
2.
39
12541
.
1221
6.
1
4914
Northeast
region:
.
152
.76
39479
.
521
2.
61
1151
.
1414
7.
7
4243
Midwest
region:
.
181
.91
331
1
.
574
2.
87
1
452
.
1383
6.
92
4337
Southern
region:
.
151
.76
39732
.
457
2.
29
13125
.
11
6
5.53
5424
Western
region:
.
158
.79
37994
.
523
2.
62
11466
.
1376
6.
88
436
Hispanics:
.
179
.89
336
4
.
616
3.
8
9745
.
1456
7.
28
4122
Non
hispanic
whites:
.
159
.79
37742
.
5
9
2.
54
11795
.
1281
6.
41
4682
Non
hispanic
blacks:
.
15
.75
4
4
.
474
2.
37
12662
.
13
7
6.
54
459
28
Non
hisp/
non
white/
non
black:
.
158
.79
38
1
.
591
2.
96
1
149
.
1593
7.
97
3765
All
in
ants:
.
2
4
1.
2
29448
.
837
4.
19
7167
.
332
16.
6
18
7
Nursing
in
ants (<
1
yr
old):
.
64
.32
941
.
288
1.
44
2
823
.
698
3.
49
8599
Non
nursing
in
ants (<
1
yr
old):
.
234
1.
17
25658
.
1521
7.
6
3945
.
3626
18.
13
1654
Children
1
6
yrs:
.
668
3.34
8987
.
1264
6.
32
4748
.
1973
9.
86
3
41
Children
7
12
yrs:
.
353
1.
76
17
17
.
642
3.
21
9342
.
1
88
5.
44
5513
Females
13+ (
preg/
not
nursing):
.
191
.95
31424
.
342
1.
71
17528
.
5
9
2.
54
11797
Females
13+ (
nursing):
.
148
.74
4
598
.
352
1.
76
17
23
.
623
3.
11
9632
Females
13
19 (
not
preg
or
nursing):
.
16
.8
374
5
.
311
1.
55
19293
.
676
3.38
8874
Females
2
+ (
not
preg
or
nursing):
.
99
.5
6
5
3
.
2
7
1.
4
28962
.
4
5
2.
2
14816
Females
13
5
yrs:
.
111
.55
54255
.
245
1.
23
24444
.
467
2.
34
12844
Males
13
19
yrs:
.
2
1
1.
29852
.
413
2.
6
14542
.
67
3.35
896
Males
2
+
yrs:
.
1
6
.53
56425
.
225
1.
13
26647
.
458
2.
29
131
4
Seniors
55+:
.
99
.5
6
477
.
2
3
1.
1
29619
.
4
9
2.
4
14676
29
Paci
ic:
.
156
.78
38498
.
531
2.
66
11297
.
1344
6.
72
4462
30
Attachment
5:
Chronic
Analysis
Chronic
Analysis
Using
Feeding
Study
U.
S.
Environmental
Protection
Agency
Ver.
7.
73
DEEM
Chronic
analysis
or
LINDANE
(1989
92
data)
Res
i
d
u
e
i
l
e
n
a
m
e
:
C
:\d
e
e
m
\
9
1
\R
e
v
i
s
e
d
Analysis\
12
11
1\
12
11
1RevchronicTRR.
RS7
Adjustment
actor #
2
used.
Analysis
Date
12
12
2
1/
13:
26:
48
Residue
ile
dated:
12
3
2
1/
5:
15:
47/
8
Re
erence
dose (
R
D,
Chronic) = .
16
mg/
kg
bw/
day
COMMENT
1:
Re
erence
doses
have
3X
FQPA
actored
in.
This
is
the
dietary
analysis
using
the
metabolism
and
eeding
studies.
=================================================================
==============
Total
exposure
by
population
subgroup
Total
Exposure
Population
mg/
kg
Percent
o
Subgroup
body
wt/
day
R
d
U.
S.
Population (
total)
.
54
3.
4%
U.
S.
Population (
spring
season)
.
54
3.3%
U.
S.
Population (
summer
season)
.
53
31
3.3%
U.
S.
Population (
autumn
season)
.
56
3.5%
U.
S.
Population (
winter
season)
.
53
3.3%
Northeast
region
.
53
3.3%
Midwest
region
.
6
3.
7%
Southern
region
.
51
3.
2%
Western
region
.
53
3.3%
Hispanics
.
59
3.
7%
Non
hispanic
whites
.
54
3.
4%
Non
hispanic
blacks
.
49
3.
1%
Non
hisp/
non
white/
non
black
.
56
3.5%
All
in
ants (<
1
year)
.
72
4.
5%
Nursing
in
ants
.
19
1.
2%
Non
nursing
in
ants
.
94
5.
9%
Children
1
6
yrs
.
173
1
.8%
Children
7
12
yrs
.
96
6.
%
Females
13
19 (
not
preg
or
nursing)
.
46
2.
9%
Females
2
+ (
not
preg
or
nursing)
.
29
1.
8%
Females
13
5
yrs
.
34
2.
1%
Females
13+ (
preg/
not
nursing)
.
49
32
3.
%
Females
13+ (
nursing)
.
43
2.
7%
Males
13
19
yrs
.
61
3.8%
Males
2
+
yrs
.
34
2.
1%
Seniors
55+
.
3
1.
9%
Paci
ic
Region
.
53
3.3%
| epa | 2024-06-07T20:31:43.052528 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0202-0004/content.txt"
} |
EPA-HQ-OPP-2002-0202-0005 | Supporting & Related Material | "2002-08-14T04:00:00" | null | December
11,
2001
MEMORANDUM:
SUBJECT:
Lindane
(009001):
Reregistration
Case
0315.
Revised
Product
and
Residue
Chemistry
Chapters
for
the
Lindane
Reregistration
Eligibility
Document
(RED).
DP
Barcode:
D279259.
FROM:
Thurston
G.
Morton,
Chemist
Reregistration
Branch
4
Health
Effects
Division
(7509C)
THROUGH:
Susan
V.
Hummel,
Branch
Senior
Scientist
Reregistration
Branch
4
Health
Effects
Division
(7509C)
TO:
Rebecca
Daiss,
Risk
Assessor
Reregistration
Branch
4
Health
Effects
Division
(7509C)
And
Mark
Howard/
Betty
Shackleford
Reregistration
Branch
3
Special
Review
&
Reregistration
Division
(7508C)
Attached
are
the
revised
Product
and
Residue
Chemistry
Chapters
for
the
lindane
RED.
The
chapters
were
assembled
by
Dynamac
Corporation
under
supervision
of
HED.
The
data
assessment
has
undergone
secondary
review
in
the
branch
and
has
been
revised
to
reflect
branch
policies.
This
memorandum
serves
to
update
the
Product
and
Residue
Chemistry
Chapter
(T.
Morton,
6/
7/
01,
D274754)
by
incorporating
comments
from
the
public
comment
period
and
incorporating
submissions
reviewed
by
the
Agency
since
9/
26/
00.
Only
uses
supported
for
reregistration
by
Inquinosa
are
included.
2
EXECUTIVE
SUMMARY:
Product
Chemistry
Pertinent
product
chemistry
data
remain
outstanding
for
the
Inquinosa
99.5%
T/
TGAI
concerning
product
identity,
starting
materials
and
production
process,
preliminary
analysis,
certified
limits,
oxidation/
reduction,
explodability,
storage
stability,
corrosion
characteristics,
and
UV/
visible
absorption
(OPPTS
830.1550,
1600,
1620,
1700,
1750,
6314,
6316,
6317,
6320,
and
7050).
Technical
products
registered
to
Kanoria
Chemicals
&
Industries
were
suspended
effective
12/
5/
00
for
failure
to
comply
with
a
cost
sharing
agreement
with
Inquinosa.
Therefore,
all
technical
products
registered
which
are
repackages
of
the
Kanoria
products
would
be
required
to
change
suppliers.
The
Prentiss,
Drexel,
and
Amvac
99.5%
Ts
are
repackaged
from
EPA
registered
products,
and
all
data
requirements
will
be
satisfied
by
data
for
the
technical
source
products.
Provided
that
the
registrants
submit
the
data
required
in
the
attached
data
summary
tables
for
the
lindane
T/
TGAIs,
and
either
certify
that
the
suppliers
of
beginning
materials
and
the
manufacturing
processes
have
not
changed
since
the
last
comprehensive
product
chemistry
reviews
or
submit
complete
updated
product
chemistry
data
packages,
the
Branch
has
no
objections
to
the
reregistration
of
lindane
with
respect
to
product
chemistry
data
requirements.
Residue
Chemistry
The
Agency
will
not
require
a
new
confined
rotational
crop
study
provided
the
registrants
propose
a
30
day
plantback
interval
for
leafy
vegetables
and
a
12
month
plantback
interval
for
all
other
unregistered
crops
on
all
of
their
end
use
product
labels
for
lindane.
The
registrants
have
informed
the
Agency
they
will
propose
the
specified
plantback
intervals.
A
new
nature
of
the
residue
study
is
required
for
application
of
lindane
as
a
seed
treatment
to
a
cereal
grain.
If
the
HED
Metabolism
Assessment
Review
Committee
determines
the
residues
of
concern
to
include
metabolites
in
addition
to
lindane,
then
additional
crop
field
trial
data,
magnitude
of
the
residue
in
poultry
and
cattle,
and
processing
studies
are
required.
In
addition,
an
adequate
residue
analytical
method
and
storage
stability
data
will
be
required.
3
Dietary
Exposure/
Risk
Assessment
Anticipated
residues
(DP
Barcode
D279260,
T.
Morton,
12/
4/
01)
will
be
provided
for
all
commodities
and
should
be
used
when
calculating
the
dietary
risk
associated
with
the
RED.
Although
the
database
for
lindane
is
substantially
complete,
additional
data
are
needed
to
eliminate
the
uncertainties
associated
with
the
exposure/
risk
assessment.
The
anticipated
residue
values
are
the
best
estimates
HED
can
provide
using
the
residue
data
available
at
the
time
of
the
RED.
These
values
have
an
inherent
uncertainty
associated
with
variations
in
analytical
methods,
geographical
representation
of
field
trials,
seasonal
variation
of
residue
levels,
use
of
TRR
from
metabolism
studies,
etc.
cc
:
Chem
F,
Chron
F.
Morton
,
Shallal
RDI:
ChemSAC:
9/
13/
00;
SVH:
12/
11/
01
TM,
Thurston
Morton,
Rm.
816D
CM2,
305
6691,
mail
code
7509C
4
LINDANE
Case
0315;
PC
Code
009001
D279259
Reregistration
Eligibility
Decision:
Product
Chemistry
Considerations
December
11,
2001
Contract
No.
68
W
99
053
Submitted
to:
U.
S.
Environmental
Protection
Agency
Arlington,
VA
Submitted
by:
Dynamac
Corporation
2275
Research
Boulevard
Rockville,
MD
22850
3268
5
Cl
Cl
Cl
Cl
Cl
Cl
LINDANE
REREGISTRATION
ELIGIBILITY
DECISION:
PRODUCT
CHEMISTRY
CONSIDERATIONS
Case
No.
0315;
PC
Code
009001
DESCRIPTION
OF
CHEMICAL
Lindane
(gamma
isomer
of
benzene
hexachloride,
gamma
isomer
of
hexachlorocyclohexane)
is
a
broad
spectrum
organochlorine
insecticide/
acaricide
registered
for
control
of
insects
and
other
invertebrates.
The
only
registered
food/
feed
use
is
seed
treatment
for
field
and
vegetable
crops.
Empirical
Formula:
C6
H6
Cl6
Molecular
Weight:
290.9
CAS
Registry
No.:
58
89
9
PC
Code:
009001
IDENTIFICATION
OF
ACTIVE
INGREDIENT
Lindane
is
a
white
crystalline
solid
with
a
melting
point
of
112
113
C,
specific
gravity
of
1.85,
octanol/
water
partition
coefficient
(Kow
)
of
3135,
and
vapor
pressure
of
9.4
x
10
6
mm
Hg
at
20
C.
Lindane
is
soluble
in
water
(10
ppm
at
20
C)
and
most
organic
solvents,
including
acetone
and
aromatic
and
chlorinated
hydrocarbons.
Lindane
is
only
slightly
soluble
in
mineral
oils.
Lindane
is
stable
to
light,
heat,
air,
and
strong
acids,
but
decomposes
upon
exposure
to
trichlorobenzenes
and
HCl
in
alkali.
MANUFACTURING
USE
PRODUCTS
According
to
a
search
of
the
Reference
Files
System
(REFS)
conducted
5/
29/
01,
there
are
eight
registered
manufacturing
use
products
(MPs)
under
PC
Code
009001.
The
registered
MPs
subject
to
a
reregistration
eligibility
decision
are
listed
in
Table
1.
6
Table
1.
Registered
lindane
manufacturing
use
products.
Formulation
EPA
Registry
Number
Registrant
99.5%
T
655
28
1
Prentiss
Incorporated
99.5%
T
655
393
1
99.5%
T
5481
225
1
Amvac
Chemical
Corporation
99.5%
T
19713
61
1
Drexel
Chemical
Company
99.5%
T
19713
191
1
99.5%
T
40083
1
Inquinosa
Internacional,
S.
A.
99.5%
T
66951
1
Kanoria
Chemicals
&
Industries
Ltd.
99.5%
T
66951
2
1
Repackaged
from
an
EPA
registered
product.
REGULATORY
BACKGROUND
The
Lindane
Reregistration
Standard
and
the
Addendum
to
the
Lindane
Reregistration
Standard
were
issued
6/
7/
85
and
7/
16/
85,
respectively,
and
required
additional
product
chemistry
data
concerning
lindane.
The
Lindane
Guidance
Document
dated
9/
85
reiterated
the
data
gaps
outlined
under
the
Addendum
to
the
Reregistration
Standard.
Data
submitted
in
response
to
the
Guidance
Document
for
the
lindane
T/
TGAIs
were
evaluated
in
the
Lindane
Reregistration
Standard
Update
dated
1/
31/
91
with
regard
to
adequacy
in
fulfilling
product
chemistry
requirements.
The
Centre
International
d'Etudes
du
Lindane
(CIEL)
members
(Rhone
Poulenc,
Inc.,
EM
Industries,
Inc.
(representing
Celamerck
GmbH
and
Company),
and
Inquinosa)
have
submitted
data
jointly.
Kanoria
Chemicals
and
Industries,
Inc.
became
a
member
of
CIEL
in
1994
(Letter
from
McKenna
and
Cuneo
on
behalf
of
CIEL
dated
11/
30/
94,
in
support
of
application
to
register
a
technical
lindane
product).
Prentiss
and
Amvac
previously
entered
into
data
sharing
agreements
with
CIEL
in
accordance
with
the
provisions
of
FIFRA
§3(
C)(
2)(
B)(
ii).
Technical
products
registered
to
Kanoria
Chemicals
&
Industries
were
suspended
effective
12/
5/
00
for
failure
to
comply
with
a
cost
sharing
agreement
with
Inquinosa.
The
current
status
of
the
product
chemistry
data
requirements
for
the
lindane
T/
TGAIs
is
presented
in
the
attached
data
summary
tables.
Refer
to
these
tables
for
a
listing
of
the
outstanding
product
chemistry
data
requirements.
CONCLUSIONS
Pertinent
product
chemistry
data
remain
outstanding
for
the
Inquinosa
99.5%
T/
TGAI
concerning
product
identity,
starting
materials
and
production
process,
preliminary
analysis,
certified
limits,
oxidation/
reduction,
explodability,
storage
stability,
corrosion
characteristics,
and
UV/
visible
absorption
(OPPTS
830.1550,
1600,
1620,
1700,
1750,
6314,
6316,
6317,
6320,
and
7050).
7
Technical
products
registered
to
Kanoria
Chemicals
&
Industries
were
suspended
effective
12/
5/
00
for
failure
to
comply
with
a
cost
sharing
agreement
with
Inquinosa.
Therefore,
all
technical
registered
which
are
repackages
of
the
Kanoria
products
would
be
required
to
change
suppliers.
The
Kanoria
products
are
shown
in
attached
data
summary
tables
for
informational
purposes
only.
The
Prentiss,
Drexel,
and
Amvac
99.5%
Ts
are
repackaged
from
EPA
registered
products,
and
all
data
requirements
will
be
satisfied
by
data
for
the
technical
source
products.
Provided
that
the
registrants
submit
the
data
required
in
the
attached
data
summary
tables
for
the
lindane
T/
TGAIs,
and
either
certify
that
the
suppliers
of
beginning
materials
and
the
manufacturing
processes
have
not
changed
since
the
last
comprehensive
product
chemistry
reviews
or
submit
complete
updated
product
chemistry
data
packages,
HED
has
no
objections
to
the
reregistration
of
lindane
with
respect
to
product
chemistry
data
requirements.
AGENCY
MEMORANDA
CITED
IN
THIS
DOCUMENT
DP
Barcode:
D211047
Subject:
RD
Product
Chemistry
Review
for
EPA
File
Symbol
Number
66951
R,
Kanoria
Lindane
Crystals
From:
S.
Mathur
To:
G.
Larocca
Dated:
3/
21/
95
MRID(
s):
43498201
43498203
DP
Barcode:
D211063
Subject:
RD
Product
Chemistry
Review
for
EPA
File
Symbol
Number
66951
E,
Kanoria
Lindane
Powder
From:
S.
Mathur
To:
G.
Larocca
Dated:
3/
21/
95
MRID(
s):
43498201
43498203
PRODUCT
CHEMISTRY
CITATIONS
Bibliographic
citations
include
only
MRIDs
containing
data
which
fulfill
data
requirements.
References
(cited):
00072468
Hooker
Chemical
&
Plastics
Corporation
(19??)
Product
Chemistry
Data:
Lindane
HGI.
(Unpublished
study
received
May
7,
1981
under
935
17;
CDL:
245029
A)
00102995
Zoecon
Corp.
(1981)
[Study
of
the
Chemical
Lindane].
(Compilation;
unpublished
study
received
Sep
15,
1981
under
20954
107;
CDL:
246026
A)
00118712
Commerce
Industrial
Chemicals,
Inc.
(1969)
Laboratory
Report:
[Lindane]:
Lab
No.
C11,131,
Supplement
#1.
(Unpublished
study
received
May
12,
1969
under
10531
1;
submitted
by
Petland
Products,
Inc.,
Chicago,
IL;
CDL:
026276
A)
8
00118743
Makhteshim
Beer
Sheva
Chemical
Works,
Ltd.
(1976)
[Chemistry
of
Lindane].
(Compilation;
unpublished
study
received
Jul
11,
1978
under
11678
16;
CDL:
234441
A)
00160127
Inquinosa
(19??)
Synthesis
of
Lindane.
Unpublished
study.
4
p.
00160129
Buys,
M.
(1986)
Lindane...
Product
Identity
and
Composition...
Discussion
of
the
Formation
of
Impurities:
Report
AG/
CRLD/
AN/
MB/
ID/
15274.86.
Unpublished
study
prepared
by
Rhone
Poulenc
Agrochimie.
10
p.
00160130
Mirfakhrae,
K.;
Norris,
F.
(1986)
Determination
of
the
Octanol/
Water
Partition
Coefficient
of
Lindane:
Ref.
No.
86/
BHL/
191/
AG:
ASD
No.
86/
187.
Unpublished
study
prepared
by
Rhone
Poulenc
Inc.
26
p.
00164782
Viziere,
G.
(1986)
Lindane:
Analysis
and
Certification
of
Product
Ingredients:
AG/
CRLD/
AN/
MB/
ID/
15871.86.
Unpublished
study
prepared
by
Rhone
Poulenc
Agrochimie.
57
p.
00164783
Buys,
M.
(1986)
Lindane:
Analytical
Data
for
the
Technical
Grade
Lindane
Produced
by
Inquinosa:
Report
AG/
CRLD/
AN/
MB/
ID/
158874.86.
Unpublished
study
prepared
by
Rhone
Poulenc
Agrochimie.
9
p.
43498201
Brookman,
D.;
Curry,
K.
(1994)
The
Product
Chemistry
of
Kanoria
Lindane
(Product
Identity
and
Disclosure
of
Ingredients).
Unpublished
study
prepared
by
Technology
Sciences
Group,
Inc.
35
p.
43498202
Brookman,
D.;
Curry,
K.
(1994)
The
Product
Chemistry
of
Kanoria
Lindane
(Analysis
and
Certification
of
Product
Ingredients).
Unpublished
study
prepared
by
Technology
Sciences
Group,
Inc.
49
p.
43498203
Brookman,
D.;
Curry,
K.
(1994)
The
Product
Chemistry
of
Kanoria
Lindane
(Physical
and
Chemical
Characteristics).
Unpublished
study
prepared
by
Technology
Sciences
Group,
Inc.
18
p.
9
Case
No.
0315
PC
Code:
009001
Case
Name:
Lindane
Registrant:
Prentiss,
Inc.
Product(
s):
99.5%
Ts
(EPA
Reg.
Nos.
655
28
and
655
393)
PRODUCT
CHEMISTRY
DATA
SUMMARY
Guideline
Number
Requirement
Are
Data
Requirements
Fulfilled?
1
MRID
Number
2
830.1550
Product
identity
and
composition
Y
CSF
4/
21/
97
(655
28)
CSF
4/
23/
97
(655
393)
830.1600
Description
of
materials
used
to
produce
the
product
N/
A
830.1620
Description
of
production
process
N/
A
830.1670
Discussion
of
formation
of
impurities
N/
A
830.1700
Preliminary
analysis
N/
A
830.1750
Certified
limits
Y
CSF
4/
21/
97
(655
28)
CSF
4/
23/
97
(655
393)
830.1800
Enforcement
analytical
method
N/
A
830.6302
Color
N/
A
830.6303
Physical
state
N/
A
830.6304
Odor
N/
A
830.6313
Stability
to
normal
and
elevated
temperatures,
metals,
and
metal
ions
N/
A
830.6314
Oxidation/
reduction:
chemical
incompatability
N/
A
830.6315
Flammability
N/
A
830.6316
Explodability
N/
A
830.6317
Storage
stability
N/
A
830.6319
Miscibility
N/
A
830.6320
Corrosion
characteristics
N/
A
830.7000
pH
N/
A
830.7050
UV/
visible
absorption
N/
A
830.7100
Viscosity
N/
A
830.7200
Melting
point/
melting
range
N/
A
830.7220
Boiling
point/
boiling
range
N/
A
830.7300
Density/
relative
density/
bulk
density
N/
A
830.7370
Dissociation
constants
in
water
N/
A
830.7550
Partition
coefficient
(n
octanol/
water),
shake
flask
method
N/
A
830.7840
Water
solubility:
column
elution
method;
shake
flask
method
N/
A
830.7950
Vapor
pressure
N/
A
1
Y
=
Yes;
N
=
No;
N/
A
=
Not
Applicable.
The
Prentiss
technical
products
are
repackaged
from
EPA
registered
products;
data
requirements
will
be
satisfied
by
data
for
the
source
products.
2
The
CSFs
were
obtained
from
the
product
jackets.
10
Case
No.
0315
PC
Code:
009001
Case
Name:
Lindane
Registrant:
Amvac
Chemical
Corp.
Product(
s):
99.5%
T
(EPA
Reg.
No.
5481
225)
PRODUCT
CHEMISTRY
DATA
SUMMARY
Guideline
Number
Requirement
Are
Data
Requirements
Fulfilled?
1
MRID
Number
2
830.1550
Product
identity
and
composition
N
3
CSF
6/
19/
86
830.1600
Description
of
materials
used
to
produce
the
product
N/
A
830.1620
Description
of
production
process
N/
A
830.1670
Discussion
of
formation
of
impurities
N/
A
830.1700
Preliminary
analysis
N/
A
830.1750
Certified
limits
N
3
CSF
6/
19/
86
830.1800
Enforcement
analytical
method
N/
A
830.6302
Color
N/
A
830.6303
Physical
state
N/
A
830.6304
Odor
N/
A
830.6313
Stability
to
normal
and
elevated
temperatures,
metals,
and
metal
ions
N/
A
830.6314
Oxidation/
reduction:
chemical
incompatability
N/
A
830.6315
Flammability
N/
A
830.6316
Explodability
N/
A
830.6317
Storage
stability
N/
A
830.6319
Miscibility
N/
A
830.6320
Corrosion
characteristics
N/
A
830.7000
pH
N/
A
830.7050
UV/
visible
absorption
N/
A
830.7100
Viscosity
N/
A
830.7200
Melting
point/
melting
range
N/
A
830.7220
Boiling
point/
boiling
range
N/
A
830.7300
Density/
relative
density/
bulk
density
N/
A
830.7370
Dissociation
constants
in
water
N/
A
830.7550
Partition
coefficient
(n
octanol/
water),
shake
flask
method
N/
A
830.7840
Water
solubility:
column
elution
method;
shake
flask
method
N/
A
830.7950
Vapor
pressure
N/
A
1
Y
=
Yes;
N
=
No;
N/
A
=
Not
Applicable.
The
available
CSF
indicates
that
the
Amvac
technical
product
is
repackaged
from
EPA
registered
products
which
have
been
canceled
(1/
28/
98).
If
the
product
is
repackaged
from
a
currently
registered
product,
data
requirements
will
be
satisfied
by
data
for
the
source
product;
otherwise,
additional
product
chemistry
data
may
be
required.
2
The
CSF
was
reviewed
in
the
Lindane
Reregistration
Standard
Update
dated
1/
31/
91.
3
The
CSF
must
be
revised
to
cite
the
current
registered
source(
s)
of
the
technical
product
(PPIS
Deficiency
Notice,
11/
1/
99,
J.
Hinkle).
11
Case
No.
0315
PC
Code:
009001
Case
Name:
Lindane
Registrant:
Drexel
Chemical
Company
Product(
s):
99.5%
Ts
(EPA
Reg.
Nos.
19713
61
and
19713
191)
PRODUCT
CHEMISTRY
DATA
SUMMARY
Guideline
Number
Requirement
Are
Data
Requirements
Fulfilled?
1
MRID
Number
2
830.1550
Product
identity
and
composition
Y
CSFs
2/
25/
98
830.1600
Description
of
materials
used
to
produce
the
product
N/
A
830.1620
Description
of
production
process
N/
A
830.1670
Discussion
of
formation
of
impurities
N/
A
830.1700
Preliminary
analysis
N/
A
830.1750
Certified
limits
Y
3
CSFs
2/
25/
98
830.1800
Enforcement
analytical
method
N/
A
830.6302
Color
N/
A
830.6303
Physical
state
N/
A
830.6304
Odor
N/
A
830.6313
Stability
to
normal
and
elevated
temperatures,
metals,
and
metal
ions
N/
A
830.6314
Oxidation/
reduction:
chemical
incompatability
N/
A
830.6315
Flammability
N/
A
830.6316
Explodability
N/
A
830.6317
Storage
stability
N/
A
830.6319
Miscibility
N/
A
830.6320
Corrosion
characteristics
N/
A
830.7000
pH
N/
A
830.7050
UV/
visible
absorption
N/
A
830.7100
Viscosity
N/
A
830.7200
Melting
point/
melting
range
N/
A
830.7220
Boiling
point/
boiling
range
N/
A
830.7300
Density/
relative
density/
bulk
density
N/
A
830.7370
Dissociation
constants
in
water
N/
A
830.7550
Partition
coefficient
(n
octanol/
water),
shake
flask
method
N/
A
830.7840
Water
solubility:
column
elution
method;
shake
flask
method
N/
A
830.7950
Vapor
pressure
N/
A
1
Y
=
Yes;
N
=
No;
N/
A
=
Not
Applicable.
The
Drexel
technical
products
are
repackaged
from
EPA
registered
products;
data
requirements
will
be
satisfied
by
data
for
the
source
products.
Data
previously
submitted
by
Drexel
in
support
of
the
reregistration
of
these
products
are
no
longer
applicable.
2
The
CSFs
were
obtained
from
the
product
jackets.
3
The
CSFs
should
be
revised
to
propose
certified
limits
for
the
active
ingredient
which
reflect
the
actual
levels
in
the
technical
products.
12
Case
No.
0315
PC
Code:
009001
Case
Name:
Lindane
Registrant:
Inquinosa
Internacional,
S.
A.
Product(
s):
99.5%
Ts
(EPA
Reg.
No.
40083
1)
PRODUCT
CHEMISTRY
DATA
SUMMARY
Guideline
Number
Requirement
Are
Data
Requirements
Fulfilled?
1
MRID
Number
2
830.1550
Product
identity
and
composition
N
3
830.1600
Description
of
materials
used
to
produce
the
product
N
4
00160127
830.1620
Description
of
production
process
N
5
00160127
830.1670
Discussion
of
formation
of
impurities
Y
00160129
830.1700
Preliminary
analysis
N
6
00164783
830.1750
Certified
limits
N
3
830.1800
Enforcement
analytical
method
Y
7
00164782
830.6302
Color
Y
00072468
830.6303
Physical
state
Y
00118743
830.6304
Odor
Y
00102995
830.6313
Stability
to
normal
and
elevated
temperatures,
metals,
and
metal
ions
Y
00072468
830.6314
Oxidation/
reduction:
chemical
incompatability
N
830.6315
Flammability
N/
A
8
830.6316
Explodability
N
830.6317
Storage
stability
N
830.6319
Miscibility
N/
A
8
830.6320
Corrosion
characteristics
N
830.7000
pH
N/
A
9
830.7050
UV/
visible
absorption
N
10
830.7100
Viscosity
N/
A
8
830.7200
Melting
point/
melting
range
Y
00118743
830.7220
Boiling
point/
boiling
range
N/
A
8
830.7300
Density/
relative
density/
bulk
density
Y
00072468
830.7370
Dissociation
constants
in
water
N/
A
9
830.7550
Partition
coefficient
(n
octanol/
water),
shake
flask
method
Y
00160130
830.7840
Water
solubility:
column
elution
method;
shake
flask
method
Y
00118712
830.7950
Vapor
pressure
Y
00118743
1
Y
=
Yes;
N
=
No;
N/
A
=
Not
Applicable.
A
CSF
for
the
Inquinosa
technical
product
was
not
available
from
the
product
jacket.
Until
a
current
CSF
is
available
for
comparison,
the
Agency
cannot
ascertain
whether
TGAI
data
(physical/
chemical
data)
from
other
CIEL
members
are
applicable
to
the
Inquinosa
product.
2
Bolded
references
were
reviewed
in
the
Lindane
Reregistration
Standard
dated
6/
7/
85
and
all
other
references
were
reviewed
in
the
Lindane
Reregistration
Standard
Update
dated
1/
31/
91.
3
An
updated
CSF
is
required
for
evaluation
of
the
product
chemistry
data
(Lindane
Reregistration
Standard
Update
dated
1/
31/
91).
13
4
Information
is
required
concerning
the
relative
amounts
and
order
in
which
the
starting
materials
are
added.
5
Additional
information
is
required
concerning:
(I)
clarification
as
to
whether
the
process
is
a
batch
or
continuous
process;
(ii)
the
duration
of
each
step
and
the
entire
process;
(iii)
description
of
the
equipment
used;
and
(iv)
quality
control
measures
used
to
ensure
the
integrity
of
the
product.
6
Data
demonstrating
that
the
method
used
for
analysis
of
dioxins
and
dibenzofurans
can
quantitate
the
2,
3,
7,
8TCDD
reference
standard
to
0.
1
ppb
must
be
provided.
7
If
the
CIPAC
normalized
4
gamma/
1/
M/
1
cryoscopic
method
is
to
be
used
for
enforcement
of
certified
limits
of
the
active
ingredient,
then
a
complete
description
of
the
method,
along
with
supporting
validation
data,
is
required.
8
Data
are
not
required
because
the
TGAI/
MP
is
a
solid
at
room
temperature.
9
Data
were
not
required
by
the
Lindane
Registration
Standard
concerning
pH
and
dissociation
constant.
10
The
OPPTS
Series
830,
Product
Properties
Test
Guidelines
require
data
pertaining
to
UV/
visible
absorption
for
the
PAI.
14
LINDANE
Case
0315;
PC
Code
009001
D279259
Reregistration
Eligibility
Decision
Residue
Chemistry
Considerations
December
11,
2001
Contract
No.
68
W
99
053
Submitted
to:
U.
S.
Environmental
Protection
Agency
Arlington,
VA
Submitted
by:
Dynamac
Corporation
The
Dynamac
Building
2275
Research
Boulevard
Rockville,
MD
20850
3268
15
LINDANE
REREGISTRATION
ELIGIBILITY
DECISION
RESIDUE
CHEMISTRY
CONSIDERATIONS
Case
0315;
PC
Code
009001
TABLE
OF
CONTENTS
page
INTRODUCTION
.........................................................
16
REGULATORY
BACKGROUND
.............................................
16
SUMMARYOFSCIENCE
FINDINGS
.........................................
17
GLN
860.1200:
Directions
for
Use
........................................
17
GLN
860.1300:
Nature
of
the
Residue
Plants
...............................
18
GLN
860.1300:
Nature
of
the
Residue
Animals
..............................
18
GLN
860.1340:
Residue
Analytical
Methods
.................................
19
GLN
860.1360:
Multiresidue
Methods
.....................................
20
GLN
860.1380:
Storage
Stability
Data
.....................................
21
GLN
860.1500:
Crop
Field
Trials
.........................................
21
GLN
860.1520:
Processed
Food/
Feed
......................................
23
GLN
860.1480:
Meat,
Milk,
Poultry,
Eggs
..................................
23
GLN
860.1400:
Water,
Fish,
and
Irrigated
Crops
.............................
26
GLN
860.1460:
Food
Handling
...........................................
26
GLN
860.1850
and
860.1900:
Confined/
Field
Accumulation
in
Rotational
Crops
.....
26
TOLERANCE
REASSESSMENT
SUMMARY
...................................
39
Tolerances
Listed
Under
40
CFR
§180.133
..................................
39
Tolerances
To
Be
Proposed
Under
40
CFR
§180.133
...........................
40
PendingTolerancePetitions
..............................................
40
CODEXHARMONIZATION.................................................
43
DIETARYEXPOSUREASSESSMENT
........................................
45
AGENCYMEMORANDARELEVANTTOREREGISTRATION
....................
46
MASTERRECORDIDENTIFICATIONNUMBERS
..............................
50
16
Cl
Cl
Cl
Cl
Cl
Cl
LINDANE
REREGISTRATION
ELIGIBILITY
DECISION
RESIDUE
CHEMISTRY
CONSIDERATIONS
Case
0315;
PC
Code
009001
INTRODUCTION
Lindane
(gamma
isomer
of
benzene
hexachloride,
gamma
isomer
of
hexachlorocyclohexane)
is
a
broad
spectrum
organochlorine
insecticide/
acaricide
registered
for
control
of
insects
and
other
invertebrates
on
a
wide
variety
of
field
crops
and
vegetable
crops
(seed
treatment
only).
According
to
a
REFS
search,
conducted
on
5/
29/
01,
there
are
approximately
34
federally
registered
end
use
products
(EPs)
containing
lindane
as
the
active
ingredient
and
three
Section
24C
registrations.
Lindane
end
use
products
are
formulated
as
dust
(D),
wettable
powder
(WP),
emulsifiable
concentrate
(EC),
flowable
concentrate
(FlC),
and
ready
to
use
(RTU)
solution.
The
reregistration
of
lindane
is
being
supported
by
Centre
International
d'Etudes
du
Lindane
(CIEL)
and
its
member
company
holding
U.
S.
registrations,
Inquinosa,
S.
A.
Currently,
Inquinosa
does
not
have
any
registered
lindane
end
use
products.
In
1993,
CIEL
offered
to
voluntarily
cancel
all
crop
uses
of
lindane
except
seed
treatment
and
certain
non
food
uses.
The
Agency
considers
lindane
seed
treatment
as
a
food
use
requiring
tolerances
based
on
existing
data
from
radiolabeled
studies
indicating
uptake
of
residues
from
the
treated
seeds
into
the
aerial
portion
of
the
growing
crop.
REGULATORY
BACKGROUND
Lindane
is
a
List
A
reregistration
pesticide.
A
Reregistration
Standard
for
Lindane
was
issued
9/
85.
The
Residue
Chemistry
Chapter
to
the
Reregistration
Standard
was
issued
on
6/
7/
85,
an
addendum
on
9/
5/
85,
and
an
Update
on
1/
31/
91.
The
Reregistration
Standard
along
with
its
Science
Chapters
summarized
the
available
data
for
each
residue
chemistry
guideline
and
specified
what
additional
data
are
required
for
reregistration
purposes.
Data
Call
In
(DCI)
Notices
for
lindane
were
issued
by
the
Agency
on
9/
30/
91,
3/
3/
95,
10/
13/
95,
and
3/
31/
97.
The
information
contained
in
this
document
outlines
the
current
Residue
Chemistry
Science
Assessments
with
respect
to
supporting
seed
treatment
uses
of
lindane,
as
well
as
the
reregistration
of
the
pesticide.
17
In
1983,
EPA
concluded
a
major
Special
Review
effort
of
lindane
based
on
carcinogenicity,
fetotoxicity/
teratogenicity,
reproductive
effects,
and
acute
effects
on
aquatic
organisms.
This
effort
resulted
in
the
cancellation
of
indoor
uses
of
smoke
fumigation
devices
and
greatly
limited
the
use
of
pet
dips
on
dogs.
In
addition,
there
were
uses
that
were
allowed
to
continue
only
if
certain
imposed
restrictions
were
implemented.
The
restrictions
were
based
on
the
degree
of
associated
hazards,
and
included
changes
in
warning
labels,
the
wearing
of
protective
clothing,
and
restrictions
to
limit
uses
to
certified
pest
control
operators.
In
1995,
EPA
announced
(FR
Vol.
60,
No.
143,
38329
38331,
7/
26/
95)
its
decision
not
to
initiate
a
Special
Review
of
lindane
based
on
worker
health
concerns
arising
from
studies
showing
irreversible
renal
effects
in
the
rat.
The
Agency
has
determined
that
these
effects
occur
only
in
the
kidneys
of
male
rat
and
are
not
relevant
for
human
risk
assessment.
Tolerances
are
currently
established
under
40
CFR
§180.133
for
residues
of
lindane
per
se
in/
on
various
raw
agricultural
commodities
at
0.01
ppm
(pecans)
to
3
ppm
(cucumbers,
lettuce,
melons,
mushrooms,
pumpkins,
squash,
summer
squash,
and
tomatoes).
Lindane
tolerances
are
also
established
at
4
ppm
in
the
fat
of
meat
from
hogs
and
at
7
ppm
in
the
fat
of
meat
from
cattle,
goats,
horses,
and
sheep.
No
tolerances
have
been
established
for
processed
food/
feed
commodities.
Adequate
methods
are
available
for
the
enforcement
of
tolerances
for
residues
of
lindane
per
se
in/
on
plant
and
animal
commodities.
SUMMARY
OF
SCIENCE
FINDINGS
GLN
860.1200:
Directions
for
Use
The
basic
registrants,
CIEL
and
its
member
company
(Inquinosa)
presently
do
not
have
any
registered
lindane
end
use
products.
However,
it
is
noted
that
lindane
remains
registered
by
other
companies
for
use
on
a
wide
variety
of
food/
feed
crops
such
as
fruit
crops,
field
crops,
and
vegetable
crops
(including
seed
treatment)
[Source:
5/
29/
01
search
of
EPA's
REFS
database].
CIEL
and
its
member
company
have
expressed
intentions
to
support
certain
non
food
uses
and
seed
treatment
uses
of
lindane
on
cereal
grains
(including
barley,
corn,
oats,
rye,
sorghum,
and
wheat
but
excluding
rice
and
wild
rice).
The
registrants
have
submitted
PP#
9F05057,
for
the
establishment
of
time
limited
tolerances
for
residues
of
lindane
per
se
in/
on
the
RACs
of
crops
for
which
seed
treatments
are
being
proposed.
Tolerances
cannot
be
established
or
reassessed
until
an
adequate
plant
metabolism
study
is
submitted.
The
registrants
have
also
submitted
PP#
9F6022,
for
the
establishment
of
tolerances
on
lindane
per
se
in/
on
canola
for
which
seed
treatment
is
being
proposed.
Tolerances
cannot
be
established
or
reassessed
until
an
adequate
plant
metabolism
study
is
submitted
and
additional
residue
data.
A
tabular
summary
of
the
residue
chemistry
science
assessments
for
reregistration
of
lindane
is
presented
in
Table
A.
When
end
use
product
DCIs
are
developed
(e.
g.,
at
issuance
of
the
RED),
RD
should
require
that
all
end
use
product
labels
(e.
g.,
MAI
labels,
SLNs,
and
products
subject
18
to
the
generic
data
exemption)
be
amended
such
that
they
are
consistent
with
the
residue
data
which
was
submitted.
A
30
day
plantback
interval
for
leafy
vegetables
and
a
12
month
plantback
interval
for
all
other
unregistered
crops
is
required
on
all
of
their
end
use
product
labels
for
lindane.
GLN
860.1300:
Nature
of
the
Residue
Plants
The
qualitative
nature
of
lindane
residues
in
plants
reflecting
seed
treatment
is
inadequately
understood.
For
the
purpose
of
reregistration,
the
basic
registrants
are
required
to
conduct
a
new
plant
metabolism
study
on
lindane.
This
study
should
be
conducted
on
a
representative
cereal
grain,
as
the
registrants
have
indicated
that
the
only
food
uses
they
are
supporting
are
for
seed
treatment
of
these
crops.
The
new
studies
should
be
conducted
at
an
application
rate
which
will
insure
that
sufficient
14
C
residues
are
available
for
analysis.
Crop
samples
should
be
harvested
at
the
appropriate
stage.
In
addition,
care
should
be
taken
to
insure
that
radioactivity
is
not
lost
during
analysis.
Identification
of
14
C
residues
should
also
be
confirmed
using
more
than
one
method,
or
by
GC/
MS.
The
results
of
the
requested
plant
metabolism
study
will
be
considered
by
HED's
MARC
for
determination
of
terminal
residues
of
concern
in
cereal
grains.
Although
the
nature
of
the
residue
in
plants
remains
inadequately
understood
at
this
time,
HED
has
no
objection
to
proceeding
with
the
Lindane
RED
and
with
risk
assessments,
given
that
acceptable
enforcement
and
datacollection
methods
are
available
for
determining
residues
of
lindane
per
se
in/
on
plants
and
the
proposed
food/
feed
uses
of
lindane
are
limited
to
seed
treatment.
The
HED
MARC
(T.
Morton,
8/
30/
00,
D267069)
concluded
that
the
total
radioactive
residues
should
be
used
for
risk
assessment
purposes
until
adequate
plant
metabolism
studies
are
submitted.
Plant
metabolism
studies
reflecting
postemergence
foliar
application
on
apples
(MRID
40410902),
cucumbers
(MRID
40431204),
and
spinach
(MRID
40431201)
were
previously
submitted
by
the
basic
registrants
in
response
to
the
requirements
of
the
9/
85
Lindane
Reregistration
Guidance
Document.
These
studies
were
deemed
unacceptable
and
nonupgradable
because
of
several
deficiencies
including
inadequate
characterization
and
identification
of
14
C
residues.
GLN
860.1300:
Nature
of
the
Residue
Animals
The
qualitative
nature
of
the
residue
in
ruminants
is
adequately
understood.
The
basic
registrants
had
submitted
a
ruminant
metabolism
study
(MRID
44867104)
which
was
deemed
inadequate
but
upgradable.
To
upgrade
the
study,
the
registrant
was
required
to
identify
the
metabolite
labeled
LiV
in
goat
liver's
aqueous
phase
which
accounted
for
25.2
%
of
the
total
radioactivity
(0.57
ppm).
In
addition,
storage
stability
data
was
required
showing
individual
tissue
sampling
dates
and
final
analysis
dates.
The
registrant
has
recently
submitted
the
required
data
(MRID
45224101,
45224102,
and
45277201)
thus,
adequately
addressing
this
deficiency.
A
brief
summary
of
the
recently
reviewed
goat
metabolism
study
follows.
Lactating
goats
were
orally
administered
with
[
14
C]
lindane
capsules
immediately
after
morning
milking
once
per
day
for
seven
19
days
at
a
level
equivalent
to
13
ppm.
Milk
was
collected
twice
daily
and
within
24
hours
of
the
last
dose,
the
animals
were
sacrificed.
The
total
radioactive
residues
(TRR;
expressed
as
lindane
equivalents)
in
collected
samples
were
3.
46
ppm
in
fat,
2.25
ppm
in
liver,
0.
48
ppm
in
kidney,
0.
20
ppm
in
muscle,
and
0.
20
ppm
in
milk.
The
parent,
lindane
was
the
major
residue
identified
in
all
goat
matrices
and
accounted
for
approximately
56%
of
the
TRR
in
milk
fat,
85%
of
the
TRR
in
fat,
81%
of
the
TRR
in
muscle,
36%
of
the
TRR
in
kidney,
and
16%
of
the
TRR
in
liver.
Other
metabolites
present
were:
gamma
pentachlorocyclohexene
(PCCH);
1,2,4
trichlorobenzene;
gamma
tetrachlorocyclohexene
(TCCH);
1,2
dichlorobenzene,
a
glutathione
conjugate
of
a
dichlorophenol,
and
a
conjugate
of
a
monochlorophenol.
The
qualitative
nature
of
the
residue
in
poultry
is
adequately
understood.
A
poultry
metabolism
study
(MRIDs
40271301
and
44405404),
submitted
by
the
registrants
in
response
to
the
9/
85
Lindane
Reregistration
Guidance
Document,
has
recently
been
upgraded
to
acceptable
status.
A
brief
summary
of
the
poultry
metabolism
study
follows.
Laying
hens
were
dosed
with
[
14
C]
lindane
at
levels
equivalent
to
1.2
ppm
or
120
ppm
in
the
diet
for
four
consecutive
days.
Radioactive
residues
accumulated
to
the
greatest
extent
in
fatty
tissues.
In
high
dose
hens,
TRR
levels
were
highest
in
fat
(96.98
ppm)
and
lowest
in
breast
muscle
(1.44
ppm).
TRR
levels
were
proportionally
less
in
tissues
of
low
dose
hens
(fat,
1.
26
ppm;
breast
muscle
0.
02
ppm).
In
eggs
of
high
dose
hens,
14
C
residues
peaked
on
Day
4
at
10.83
ppm
in
yolks
and
0.21
ppm
in
whites.
Lindane
was
the
major
residue
component
identified
and
accounted
for
approximately
95%
of
the
TRR
in
egg
yolks,
71
86%
of
the
TRR
in
muscle,
skin,
and
fat,
and
52%
of
the
TRR
in
liver.
Other
metabolites
that
were
identified
included:
1,2,4
trichlorobenzene;
1,3,5
trichlorobenzene
and
dichlorobenzene(
s);
tetrachlorobenzene
(either
1,2,4,5
or
1,2,3,4);
PCCH;
1,
2,
3,
4tetrachlorobenzene
tetrachlorocyclohexene;
1,2,3,4,5
pentachlorobenzene;
and
hexachlorocyclohexene.
The
results
of
the
ruminant
and
poultry
metabolism
studies
will
be
presented
to
HED's
MARC
for
determination
of
terminal
residue
of
concern
in
eggs,
milk,
and
animal
tissues
when
an
acceptable
plant
metabolism
study
is
submitted.
If
the
Committee
determines
that
lindane
per
se
is
the
only
residue
of
concern
requiring
regulation,
then
the
existing
storage
stability
data
for
poultry
commodities,
the
analytical
method
used
for
data
collection,
and
the
poultry
feeding
study
will
be
upgraded
to
acceptable
status.
The
HED
MARC
(T.
Morton,
8/
30/
00,
D267069)
concluded
that
the
total
radioactive
residues
should
be
used
for
risk
assessment
purposes
until
an
adequate
plant
metabolism
study
is
submitted.
GLN
860.1340:
Residue
Analytical
Methods
Because
the
nature
of
the
residue
in
plants
resulting
from
seed
treatment
uses
have
not
been
adequately
delineated,
the
adequacy
of
the
available
analytical
methods
cannot
be
determined.
The
registrants
are
reminded
that
radiovalidation
of
enforcement
method(
s)
is
a
reregistration
requirement;
therefore,
representative
samples
from
the
requested
plant
metabolism
study
should
be
used
for
radiovalidation
and
analyzed
by
the
existing
or
proposed
enforcement
method(
s)
to
determine
whether
total
toxic
residues
are
extracted
from
weathered
samples.
20
Adequate
methods
are
available
for
determination
of
residues
of
lindane
per
se
in/
on
plant
and
animal
commodities.
The
Pesticide
Analytical
Manual
(PAM)
Vol.
II
lists
Methods
I
and
II
for
the
analysis
of
mixed
isomers
of
1,
2,
3,
4,
5,
6
hexachlorocyclohexane
in/
on
plant
and
animal
commodities.
Method
I
is
a
multiresidue
method
(see
"GLN
860.1360:
Multiresidue
Methods"
section)
for
chlorinated
compounds.
Method
II
is
based
upon
the
official
final
AOAC
method
(1990,
15th
edition
of
AOAC)
and
is
suitable
for
determining
residues
of
lindane
in/
on
AOAC
Group
I
nonfatty
foods
(vegetables
and
fruits),
dairy
products,
fish,
and
eggs.
The
stated
limit
of
detection
of
Method
II
is
0.
05
ppm
for
most
commodities.
Adequate
data
collection
methods
have
been
submitted
for
detection
of
lindane
per
se
in/
on
cucumbers
and
spinach.
The
analytical
procedures
for
detecting
lindane
in
cucumbers
and
spinach
are
essentially
the
same.
Residues
of
lindane
are
extracted
with
acetonitrile,
partitioned
with
hexane:
acetonitrile,
cleaned
up
using
Florisil
column
chromatography,
and
analyzed
by
gas
chromatography
with
electron
capture
detection
(ECD);
the
reported
detection
limit
was
0.01
ppm.
Based
on
acceptable
method
validation
recoveries,
the
Agency
has
deemed
the
GC/
ECD
method
to
be
adequate
for
determining
residues
of
lindane
per
se
in
nonfatty
crops.
A
GC/
MS
method
(SOP#
Meth
109)
entitled
"Determination
of
Lindane
in
Wheat
and
Canola
Matrices"
was
utilized
as
the
data
collection
method
in
a
recently
submitted
wheat
field
study.
Briefly,
residues
in/
on
wheat
forage,
hay,
grain,
and
straw
samples
were
extracted
with
acetonitrile
and
water.
The
water
was
salted
out,
and
an
aliquot
of
the
remaining
acetonitrile
extract
was
purified
by
means
of
a
hexane
solvent
partition,
gel
permeation
chromatography,
dichloromethane/
salt
water
solvent
partition,
and
a
carbon
black
solid
phase
extraction
cartridge
cleanup.
Detection
and
quantitation
were
conducted
using
a
gas
chromatograph
equipped
with
a
mass
selective
detector
(GC/
MS).
The
LOQ
was
0.
005
ppm.
A
data
collection
method,
based
on
the
AOAC
method,
was
also
submitted
for
detection
of
lindane
per
se
in
eggs,
milk,
and
animal
tissues.
The
Agency
previously
required
an
EPA
method
validation
for
the
submitted
method
if
lindane
tolerances
for
lean
animal
tissues
were
to
be
established
because
the
AOAC
method
did
not
describe
techniques
which
the
registrant's
method
contained
(e.
g.,
gel
permeation
chromatography
and
rotary
evaporation).
The
FDA
method
now
utilizes
these
techniques;
therefore,
the
requirement
for
a
petition
method
validation
was
conditionally
waived
provided
HED's
MARC
determines
that
lindane
per
se
is
the
only
residue
of
concern
in
animal
commodities.
GLN
860.1360:
Multiresidue
Methods
The
10/
99
PESTDATA
database
(PAM,
Vol.
I,
Appendix
I)
contains
data
concerning
the
applicability
of
multiresidue
methods
to
lindane.
Lindane
is
completely
recovered
(>
80%
recovery)
using
protocols
302
(Luke
method),
303
(Mills,
Onley,
and
Gaither
method),
and
304
(Mills
method)
for
fatty
and
non
fatty
foods.
Should
the
HED
MARC
determine
that
lindane
metabolites
other
than
the
parent
should
be
regulated,
the
Agency
will
require
the
registrants
to
submit
additional
multiresidue
methods
test
data
for
the
metabolites
of
concern.
21
GLN
860.1380:
Storage
Stability
Data
The
specifics
of
reregistration
requirements
for
storage
stability
data
in
plants
and
animals
cannot
be
ascertained
until
acceptable
plant
metabolism
studies
are
available,
and
the
HED
MARC
has
determined
the
terminal
residues
of
concern.
Assuming
that
lindane
per
se
is
the
terminal
residue
of
concern
and
provided
the
additional
temperature
information
is
submitted,
the
available
storage
stability
data
for
lindane
support
the
storage
conditions
and
intervals
of
samples
collected
from
existing
crop
field
trials
and
livestock
feeding
studies.
A
summary
of
available
storage
stability
data
for
lindane
per
se
is
summarized
below.
Raw
agricultural
and
processed
commodities:
Residues
of
lindane
per
se
are
relatively
stable
under
frozen
(
20
C)
storage
conditions
for
up
to
8
months
in/
on
cucumbers
and
spinach
and
for
approximately
14
months
in/
on
tomatoes
and
wheat
forage.
Lindane
residues
are
stable
in
wheat
grain,
wheat
hay,
and
wheat
straw
for
up
to
approximately
18
months
when
stored
under
frozen
conditions.
Lindane
residues
in
canola
seed
were
stable
for
up
to
6.
5
months
when
stored
under
frozen
conditions
(no
temperature
given).
Lindane
residues
were
stable
for
up
to
2
months
in
canola
oil
and
1.
5
months
in
canola
meal
when
stored
under
frozen
conditions
(no
temperature
given).
The
registrant
is
required
to
submit
additional
storage
stability
data
(temperature
logs)
specifying
the
storage
conditions
of
the
canola
storage
stability
samples.
Assuming
that
lindane
per
se
is
the
terminal
residue
of
concern,
these
data
support
the
storage
conditions
and
intervals
of
samples
collected
from
existing
crop
field
trials.
Animal
commodities:
Residues
of
lindane
per
se
are
relatively
stable
in
eggs,
milk,
and
edible
tissues
of
animals
stored
frozen
(
18
C)
for
up
to
9
months.
Assuming
that
lindane
per
se
is
the
terminal
residue
of
concern,
these
data
support
the
storage
conditions
and
intervals
of
samples
collected
from
existing
ruminant
and
poultry
feeding
studies.
GLN
860.1500:
Crop
Field
Trials
A
translocation
study
(MRID
40431207)
formed
the
basis
for
food
use
classification
of
lindane
when
the
pesticide
is
applied
as
a
seed
treatment.
In
this
study,
[
14
C]
lindane
was
applied
as
a
seed
treatment
to
corn
(field
and
sweet),
mustard,
radish,
spinach,
sugar
beet,
and
wheat
at
approximately
1x
the
label
rate.
The
treated
seeds
were
then
planted
outdoors
in
55
gallon
drum
halves
and
allowed
to
grow
under
simulated
normal
agricultural
practices.
Samples
of
immature
and
mature
crop
commodities
were
analyzed
for
total
14
C,
and
some
fractions
were
extracted
with
hexane
and
analyzed
by
a
GC
method
for
total
lindane.
The
above
study
failed
to
adequately
identify
radioactive
residues
in/
on
all
commodities
grown
from
treated
seed.
Nonetheless,
with
the
possible
exception
of
wheat
grain
and
foliage,
residues
were
characterized
to
be
not
associated
with
biological
molecules
(e.
g.,
amino
acid,
sugar,
etc.)
that
have
incorporated
the
radiolabel.
The
total
residues
found,
the
hexane
extractable
residues,
and
the
residues
attributable
to
lindane
are
summarized
in
the
table
below.
Should
the
HED
MARC
determine
that
lindane
metabolites
other
than
the
parent
should
be
regulated,
the
Agency
will
require
the
registrants
to
submit
additional
crop
field
trial
data
for
all
residues
of
concern.
22
Table
1.
Residues
in
Various
Crops
Grown
from
Seed
Treated
with
Lindane.
Crop
Matrix
TRR
(ppm)
Radioactivity
in
Hexane
Extract
Residues
Attributed
to
Lindane
Radish
Root
0.056
0.038
ppm;
68%
TRR
0.
030
ppm;
54%
TRR
Mustard
Foliage
0.021
0.012
ppm;
57%
TRR
0.
017
ppm;
81%
TRR
1
Field
Corn
Root
0.340
0.307
ppm;
90%
TRR
0.
165
ppm;
49%
TRR
Field
Corn
Foliage
0.064
0.016
ppm;
25%
TRR
0.
008
ppm;
13%
TRR
Field
Corn
Grain
<0.
01
Sweet
Corn
Foliage
0.051
0.060
ppm;
118%
TRR
0.
012
ppm;
24%
TRR
Sweet
Corn
Grain
<0.01
Sugar
Beet
Root
(Immature)
0.297
0.175
ppm;
59%
TRR
0.
090
ppm;
30%
TRR
Sugar
Beet
Foliage
0.181
0.174
ppm;
96%
TRR
0.
035
ppm;
19%
TRR
Wheat
Foliage
2.925
0.136
ppm;
4.
6%
TRR
0.016
ppm;
0.
55%
TRR
Wheat
Grain
0.052
0.002
ppm;
3.
8%
TRR
Spinach
Leaves
0.
020
1
Lindane
exceeds
the
TRR
of
extract.
The
registrants
have
submitted
PP#
9F05057,
for
the
establishment
of
time
limited
tolerances
for
residues
of
lindane
per
se
in/
on
the
RACs
of
crops
for
which
seed
treatments
are
being
proposed.
Tolerances
cannot
be
established
or
reassessed
until
adequate
plant
metabolism
studies
are
submitted.
The
registrants
have
also
submitted
PP#
9F6022,
for
the
establishment
of
tolerances
on
lindane
per
se
in/
on
canola
for
which
seed
treatment
is
being
proposed.
Tolerances
cannot
be
established
or
reassessed
until
adequate
plant
metabolism
studies
are
submitted.
In
addition,
the
registrants
recently
submitted
acceptable
residue
data
reflecting
seed
treatment
on
wheat
RACs.
A
representative
formulation
(Lindane
30
C)
was
applied
as
a
seed
treatment
to
wheat
at
0.52
oz.
ai/
cwt
(or
330
ppm
lindane
on
the
seed).
Following
treatment,
the
treated
seeds
were
planted
in
15
diverse
geographic
locations.
Wheat
forage
samples
were
collected
at
or
near
the
jointing
stage,
the
hay
samples
at
early
flower
to
soft
dough
stage,
and
the
grain
and
straw
samples
at
normal
harvest
maturity.
Residues
of
lindane
were
nondetectable
(<
0.
005
ppm)
in/
on
all
treated
wheat
grain
and
straw
samples.
Residues
of
lindane
ranged
from
<0.005
ppm
(nondetectable)
to
0.
04
ppm
in/
on
treated
wheat
forage
and
from
<0.005
ppm
(nondetectable)
to
0.02
ppm
in/
on
treated
wheat
hay.
Additional
residue
data
would
be
required
if
the
HED
MARC
determines
residues
of
concern
include
metabolites
of
lindane
in
addition
to
lindane
per
se.
23
GLN
860.1520:
Processed
Food/
Feed
No
data
are
available
to
determine
whether
lindane
residues
of
concern
concentrate
in
the
processed
fractions
of
corn
following
seed
treatment.
A
processing
study
on
corn
is
required
for
the
purpose
of
reregistration.
A
processing
study
on
wheat
would
also
be
required
if
the
HED
MARC
determines
residues
of
concern
include
metabolites
of
lindane
in
addition
to
lindane
per
se.
A
processing
study
for
wheat
processed
fractions
is
not
being
required
if
lindane
per
se
is
the
only
residue
of
concern
(S.
Funk,
10/
31/
95,
D213401).
In
1998,
the
U.
S.
Food
and
Drug
Administration
(FDA)
monitoring
program
analyzed
a
total
of
227
samples
of
milled
grain
products
for
lindane
residues
at
an
LOQ
of
0.01
ppm.
Commodities
analyzed
included
flour
and
other
milled
products,
breakfast
foods,
and
baked
goods.
Lindane
was
not
detected
in
any
sample.
The
registrant
submitted
a
canola
processing
study
along
with
PP#
9F6022
where
lindane
residues
in/
on
canola
refined
oil,
canola
meal,
and
bleached/
deodorized
canola
oil
were
determined.
Lindane
in
canola
refined
oil
concentrated
by
a
factor
of
at
least
5.
2x.
Lindane
did
not
concentrate
in
canola
meal
and
bleached/
deodorized
canola
oil.
GLN
860.1480:
Meat,
Milk,
Poultry,
Eggs
The
nature
of
the
residue
in
plants
is
not
understood.
Upon
receipt
of
the
requested
plant
metabolism
data,
the
Agency
will:
(I)
determine
the
adequacy
of
established
tolerances
for
animal
commodities;
(ii)
calculate
the
expected
dietary
intake
for
beef
cattle,
dairy
cattle,
and
swine;
and
(iii)
re
evaluate
the
need
for
additional
feeding
studies.
It
should
be
noted
that
ruminant
(M.
Kovacs,
9/
20/
88,
CB
No.
4037)
and
poultry
feeding
(G.
Otakie,
8/
31/
88,
RCB
No.
4034)
studies
are
available
(summarized
below)
assuming
that
lindane
per
se
is
the
only
residue
of
concern
in
animals.
Ruminant
Feeding
Study
Thirteen
lactating
Holstein
cows
were
orally
administered
gelatin
capsules
containing
lindane
daily
for
28
consecutive
days.
The
cows
were
assigned
to
four
groups
(four
cows
per
dose
group
plus
one
control).
Three
of
the
four
cows
in
each
dosing
level
were
also
dermally
treated
via
a
dip
tank
on
day
21
and
28.
Lindane
residues
in
Table
2
are
from
the
single
cow
which
did
not
receive
the
dip
treatment.
Cows
were
housed
in
a
common
area.
The
administered
dose
levels
were
20
ppm,
60
ppm,
and
200
ppm
which
are
equivalent
to
143x,
426x,
and
1,418x
the
maximum
lindane
dietary
burden
of
0.
141
ppm
for
dairy
cattle
(assuming
lindane
is
the
sole
residue
of
concern).
Using
the
total
radioactive
residues
for
feed
items
as
required
by
the
HED
MARC,
the
feeding
levels
are
equivalent
to
3x,
10x,
and
34x
the
maximum
lindane
dietary
burden
for
dairy
cattle
(equivalent
to
7x,
20x,
and
67x
the
maximum
lindane
dietary
burden
for
beef
cattle).
The
calculation
of
expected
dietary
intake
for
beef
and
dairy
cattle,
using
feed
items
derived
from
proposed
seed
treatment
uses,
is
presented
in
Table
2.
The
daily
dose
was
given
to
each
cow
after
the
morning
milking.
Milk
subsamples
were
collected
for
analysis
on
days
0,
1,
3,
24
7,
14,
21,
25,
and
28.
Tissue
samples
were
collected
from
each
cow
after
sacrifice
by
exsanguination.
All
tissue
samples
were
immediately
frozen
on
dry
ice
and
stored
at
15
C
for
4
to
4½
months
prior
to
residue
analysis.
Milk
samples
were
stored
at
15
C
for
1
to
3
months
prior
to
analysis.
The
available
storage
stability
data
indicate
that
lindane
per
se
is
relatively
stable
in
eggs,
milk,
and
edible
tissues
of
animals
stored
frozen
(
18
C)
for
up
to
9
months.
These
data
support
the
storage
conditions
and
intervals
of
samples
collected
from
dairy
cattle
feeding
study.
Samples
were
analyzed
for
lindane
residues
by
validated
AOAC
Multiresidue
GLC
methodology
with
electron
capture
detection.
Table
2.
Calculation
of
maximum
dietary
burdens
of
beef
cattle,
dairy
cattle,
and
swine
for
lindane
using
feed
items
derived
from
seed
treatment.
Feed
Commodity
%
Dry
Matter
%
Diet
Reassessed
Tolerance
(ppm)
2
Dietary
Contribution
(ppm)
1
Beef
Cattle
Corn
forage
40
40
0.1
0.
100
Corn
grain
88
60
0.
01
0.
007
Total
Burden
0.107
Dairy
Cattle
Corn
forage
40
50
0.1
0.
125
Corn
grain
88
40
0.
01
0.
004
Corn
stover
83
10
0.
1
0.012
Total
Burden
0.141
Swine
Corn
grain
NA
80
0.
01
0.
008
Wheat
grain
NA
20
0.005
0.001
Total
Burden
0.009
1
Contribution
=
[reassessed
tolerance
/
%
DM]
X
%
diet).
2
Reassessed
tolerance
if
lindane
per
se
is
determined
by
the
HED
MARC
to
be
the
only
residue
of
concern.
The
results
of
the
dairy
cattle
feeding
study
are
presented
in
Table
3.
There
appears
to
be
a
linear
correlation
between
the
dose
level
and
the
residue
found
for
each
tissue
and
for
milk.
Residues
of
lindane
in
milk
plateaued
on
Day
7.
By
extrapolation
of
residue
levels
obtained
at
the
20
ppm
dosing
levels,
the
maximum
expected
residues
of
lindane
in
dairy
cattle
milk
and
tissues
are
all
below
0.
01
ppm
except
in
the
fat
where
the
predicted
maximum
residue
is
0.084
ppm.
25
Table
3.
Residues
of
lindane
in
milk
and
meat
of
dairy
cattle
dosed
with
lindane
in
the
diet
at
20,
60
and
200
ppm
for
28
consecutive
days.
Tissue
Lindane
Residues
(ppm)
Obtained
at
Various
Dosing
Levels
20
ppm
60
ppm
200
ppm
Liver
0.
10
0.
19
0.
72
Kidney
0.34
1.07
4.57
Heart
1.
23
1.
56
10.
3
Muscle
0.97
1.80
8.75
Fat
11.9
20.2
158.1
Milk
Day
7
0.
47
1.
08
5.
20
Day
14
0.17
0.75
3.12
Day
21
0.19
1.02
7.08
Day
25
0.31
1.19
5.49
Day
28
0.67
1.90
10.81
Poultry
Feeding
Study
Sixty
White
Leghorn
laying
hens
were
orally
administered
gelatin
capsules
containing
lindane
daily
for
28
consecutive
days.
The
hens
were
assigned
to
fourteen
groups
(four
hens
per
group,
4
groups
per
dose
level
plus
two
control
groups).
The
administered
dose
levels
were
1.
5
ppm,
4.
5
ppm,
and
15
ppm
which
are
equivalent
to
15x,
45x,
and
150x
the
maximum
lindane
dietary
burden
of
0.10
ppm
for
poultry
as
calculated
by
the
registrant.
The
daily
dose
was
given
to
each
hen
at
the
daily
egg
sampling
and
feeding.
Egg
samples
were
collected
for
analysis
on
days
0,
1,
3,
7,
14,
21,
25,
and
28.
Tissue
samples
were
collected
from
each
hen
after
sacrifice
by
exsanguination.
Tissue
samples
were
composited
by
group
(four
hens).
All
tissue
samples
were
immediately
frozen
on
dry
ice
and
stored
at
15
C
for
a
maximum
of
5
months
prior
to
residue
analysis.
Egg
samples
were
stored
at
15
C
for
a
maximum
of
5
months
prior
to
analysis.
The
available
storage
stability
data
indicate
that
lindane
per
se
is
relatively
stable
in
eggs,
milk,
and
edible
tissues
of
animals
stored
frozen
(
18
C)
for
up
to
9
months.
These
data
support
the
storage
conditions
and
intervals
of
samples
collected
from
the
poultry
feeding
study.
Samples
were
analyzed
for
lindane
residues
by
validated
AOAC
Multiresidue
GLC
methodology
with
electron
capture
detection.
The
results
of
the
poultry
feeding
study
are
presented
in
Table
4.
There
appears
to
be
a
linear
correlation
between
the
dose
level
and
the
residue
found
for
eggs
and
each
tissue.
Residues
of
lindane
in
eggs
plateaued
by
Day
14.
By
extrapolation
of
residue
levels
obtained
at
the
1.
5
ppm
dosing
levels,
the
maximum
expected
residues
of
lindane
in
poultry
eggs
and
tissues
are
all
below
0.01
ppm
except
in
the
kidney,
fat,
and
eggs
where
the
predicted
maximum
residues
are
0.011,
0.169,
and
0.
014
ppm,
respectively.
26
Table
4.
Residues
of
lindane
in
eggs
and
tissues
of
laying
hens
dosed
with
lindane
in
the
diet
at
1.
5,
4.
5
and
15
ppm
for
28
consecutive
days.
Tissue
Lindane
Residues
(ppm)
Obtained
at
Various
Dosing
Levels
1.5
ppm
4.5
ppm
15
ppm
Liver
0.
12
0.
51
0.
78
Kidney
0.17
0.55
2.03
Heart
0.
33
0.
89
2.
26
Gizzard
0.
10
0.
32
0.
95
Thigh
0.
19
0.
36
1.
35
Breast
0.03
0.10
0.37
Fat
2.
54
7.
75
27.65
Eggs
Day
7
0.
110
0.258
0.878
Day
14
0.216
0.609
2.14
Day
21
0.185
0.603
2.36
Day
25
0.189
0.672
2.10
Day
28
0.205
0.588
2.38
GLN
860.1400:
Water,
Fish,
and
Irrigated
Crops
Lindane
is
presently
not
registered
for
direct
use
on
water
and
aquatic
food
and
feed
crops;
therefore,
no
residue
chemistry
data
are
required
under
this
guideline
topic.
GLN
860.1460:
Food
Handling
Lindane
is
presently
not
registered
for
use
in
food
handling
establishments;
therefore,
no
residue
chemistry
data
are
required
under
this
guideline
topic.
GLN
860.1850
and
860.1900:
Confined/
Field
Accumulation
in
Rotational
Crops
The
basic
registrants
have
submitted
a
confined
rotational
crop
study
which
was
deemed
unacceptable
and
not
upgradable
because
of
inadequate
characterization
and
identification
of
residues
due
to
significant
losses
of
organosoluble
residues
during
analysis.
Although
the
study
is
inadequate
and
the
application
rate
used
(0.75
lb
ai/
A)
greatly
exceeds
the
level
of
soil
residues
that
are
likely
to
result
from
seed
treatment
uses,
the
data
indicate
that
residues
of
lindane
persist
in
the
soil
and
can
be
taken
up
by
rotational
crops
at
intervals
up
to
one
year.
For
the
purpose
of
reregistration,
the
Agency
will
not
require
a
new
confined
rotational
crop
study
provided
the
registrants
propose
a
30
day
plantback
interval
for
leafy
vegetables
and
a
12
month
plantback
interval
for
all
other
unregistered
crops
on
all
of
their
end
use
product
labels
for
lindane.
If
this
recommendation
is
not
acceptable
to
the
registrants,
then
limited
rotational
field
trial
data
are
required.
The
limited
field
trials
should
be
conducted
on
a
representative
crop
(as
defined
in
40
CFR
180.41)
at
two
sites
per
crop
for
the
following
three
crop
groups:
root
and
tuber
vegetables,
leafy
vegetables
and
small
grains
(wheat,
barley,
oats,
and
rye)
for
a
total
of
six
27
trials.
As
with
confined
studies
(OPPTS
860.1850),
soybeans
may
be
substituted
for
the
leafy
vegetable.
The
six
trials
should
be
conducted
on
crops
which
a
registrant
intends
to
have
as
rotational
crops
on
the
label.
In
addition,
some
of
the
six
trials
could
be
conducted
using
other
crops
that
are
typically
involved
in
crop
rotation
such
as
alfalfa
and
soybeans.
The
registrants
have
informed
the
Agency
they
will
propose
the
specified
plantback
intervals.
The
results
of
the
confined
rotational
crop
study
are
summarized
in
the
tables
below.
Table
5a.
Summary
of
the
characterization/
identification
of
radioactive
residues
in/
on
barley
forage
grown
in
sandy
loam
soil
treated
with
[
14
C]
lindane
at
0.
75
lb
ai/
A
(22x
the
seed
treated
barley
application
rate).
30
DAT
Barley
Forage
(TRR
=
0.
0991
ppm)
121
DAT
Barley
Forage
(TRR
=
0.
3939
ppm)
365
DAT
Barley
Forage
(TRR
=
0.
1082
ppm)
Metabolite
%TRR
ppm
%TRR
ppm
%TRR
ppm
Identified
Lindane
15.79
0.0156
26.18
0.1031
3.17
0.0034
2,4
Dichlorophenol
2.43
0.0024
1.02
0.0040
2,4,5
Trichlorophenol
2.
96
0.
0029
2.89
0.0114
2,3,4,6
Tetrachlorophenol
4.
45
0.
0175
Total
identified
21.18
0.0209
34.54
0.1360
3.17
0.0034
Characterized
Unidentified
Residues
3.
65
0.
0036
0.05
0.0002
9.31
0.0101
Total
identified/
characterized
24.83
0.0245
34.59
0.1362
12.48
0.0135
Nonextractable
51.36
0.0509
39.30
0.1548
40.39
0.0437
Table
5b.
Summary
of
the
characterization/
identification
of
radioactive
residues
in/
on
barley
straw
and
grain
grown
in
sandy
loam
soil
treated
with
[
14
C]
lindane
at
0.
75
lb
ai/
A.
30
DAT
Barley
Straw
(TRR
=
0.
3866
ppm)
121
DAT
Barley
Straw
(TRR
=
0.
9341
ppm)
30
DAT
Barley
Grain
(TRR
=
0.
0478
ppm)
Metabolite
%TRR
ppm
%TRR
ppm
%TRR
ppm
Identified
Lindane
0.
36
0.
0014
2.42
0.0226
4
Chlorophenol
16.61
0.0642
0.90
0.0084
8.79
0.0042
2,4
Dichlorophenol
3.80
0.0147
2.28
0.0213
2.09
0.0010
2,4,5
Trichlorophenol
1.
82
0.
0070
1.06
0.0099
3.35
0.0016
Total
identified
22.59
0.0873
6.66
0.0622
14.23
0.0068
Characterized
Unidentified
Residues
2.
58
0.
0100
1.73
0.0161
Acid
hydrolysate
7.
37
0.
0688
Total
identified/
characterized
25.17
0.0973
15.76
0.1471
14.23
0.0068
Nonextractable
NR
NR
78.21
0.7306
NR
NR
NR
=
not
reported
28
Table
6a.
Summary
of
the
characterization/
identification
of
radioactive
residues
in/
on
mature
carrot
root
grown
in
sandy
loam
soil
treated
with
[
14
C]
lindane
at
0.
75
lb
ai/
A.
30
DAT
Mature
Carrot
Root
(TRR
=
0.
4447
ppm)
121
DAT
Mature
Carrot
Root
(TRR
=
0.
4081
ppm)
365
DAT
Mature
Carrot
Root
(TRR
=
0.
3984
ppm)
Metabolite
%TRR
ppm
%TRR
ppm
%TRR
ppm
Identified
Lindane
47.65
0.2119
83.12
0.3392
88.78
0.3537
Pentachlorocyclohexene
5.61
0.0229
3.21
0.0128
Total
identified
47.65
0.2119
88.73
0.3621
91.99
0.3665
Characterized
Unidentified
Residues
2.
41
0.
0107
3.16
0.0129
2.81
0.0112
Total
identified/
characterized
50.06
0.2226
91.89
0.3750
94.80
0.3777
Nonextractable
1.03
0.0046
2.50
0.0102
0.90
0.0036
Table
6b.
Summary
of
the
characterization/
identification
of
radioactive
residues
in/
on
mature
carrot
tops
grown
in
sandy
loam
soil
treated
with
[
14
C]
lindane
at
0.
75
lb
ai/
A.
30
DAT
Mature
Carrot
Tops
(TRR
=
0.
0916
ppm)
121
DAT
Mature
Carrot
Tops
(TRR
=
0.
1857
ppm)
365
DAT
Mature
Carrot
Tops
(TRR
=
0.
0637
ppm)
Metabolite
%TRR
ppm
%TRR
ppm
%TRR
ppm
Identified
Lindane
69.19
0.0634
91.12
0.1692
18.45
0.0118
Total
identified
69.19
0.0634
91.12
0.1692
18.45
0.0118
Characterized
Unidentified
Residues
14.44
0.0132
2.80
0.0052
37.28
0.0237
Total
identified/
characterized
83.63
0.0766
93.92
0.1744
55.73
0.0355
Nonextractable
13.21
0.0121
10.29
0.0191
29.04
0.0409
29
Table
7.
Summary
of
the
characterization/
identification
of
radioactive
residues
in/
on
immature
and
mature
lettuce
grown
in
sandy
loam
soil
treated
with
[
14
C]
lindane
at
0.
75
lb
ai/
A.
a
30
DAT
Immature
Lettuce
(TRR
=
0.
0207
ppm)
121
DAT
Immature
Lettuce
(TRR
=
0.
0419
ppm)
30
DAT
Mature
Lettuce
(TRR
=
0.
0429
ppm)
Metabolite
%TRR
ppm
%TRR
ppm
%TRR
ppm
Identified
Lindane
137.57
0.0285
26.08
0.0109
42.80
0.0184
4
Chlorophenol
7.56
0.0032
2,4,5
Trichlorophenol
7.
02
0.
0030
2,3,4,6
Tetrachlorophenol
4.
30
0.
0018
Total
identified
137.57
0.0285
26.08
0.0109
61.68
0.0264
Characterized
Unidentified
Residues
5.
66
0.
0024
5.45
0.0023
Total
identified/
characterized
137.57
0.0285
31.74
0.0133
67.13
0.0287
Nonextractable
32.37
0.0067
24.58
0.0103
35.20
0.0151
a
Organosoluble
14
C
residues
were
0.01
ppm
from
365
day
immature
lettuce
and
121
and
365
day
mature
lettuce
samples
and
were
not
further
characterized.
(continued;
footnotes
follow)
30
Table
A.
Residue
Chemistry
Science
Assessments
for
Reregistration
of
Lindane.
GLN:
Data
Requirements
Current
Tolerances,
ppm
[40
CFR
§180.133]
Must
Additional
Data
Be
Submitted?
References
1
860.1200:
Directions
for
Use
N/
A
=
Not
Applicable
Yes
2
REFS
search
of
5/
29/
01
860.1300:
Plant
Metabolism
N/
A
Yes
3
00025707,
00060143,
00060150,
00105413,
GS
00010,
GS
00012,
GS
00013,
GS
00019,
40410902
4
,
40431201
4
,
40431204
4
,
44383001
5
,
44383002
5
,
44405403
6
860.1300:
Animal
Metabolism
N/
A
No
7
GS
00014,
GS
00015,
GS
00016,
40271301
8
,
40271302
9
,
44405404
6
,
44867104
10
,
45224101
11
,
45224102
11
,
45277201
11
860.1340:
Residue
Analytical
Methods
Plant
commodities
N/
A
Reserved
12
05006312,
GS
00018,
40431202
13
,
40431206
13
,
44383003
5
,
44383004
5
,
44909901
14
Animal
commodities
N/
A
Reserved
12
00025690,
00032233,
00099909,
05002348,
05003005,
GS
00017,
40431208
15
,
44440601
16
,
44867105
10
860.1360:
Multiresidue
Methods
N/
A
Reserved
17
860.1380:
Storage
Stability
Data
Plant
commodities
N/
A
Yes
18
40431203
19
,
40431205
19
,
41699701
20
,
44440602
16
,
44909901
14
Animal
commodities
N/
A
Reserved
21
40660502
22
,
44440603
16
,
44867106
10
Table
A
(continued).
GLN:
Data
Requirements
Current
Tolerances,
ppm
[40
CFR
§180.133]
Must
Additional
Data
Be
Submitted?
References
1
(continued;
footnotes
follow)
31
860.1500:
Crop
Field
Trials
[NOTE:
The
basic
registrants
are
supporting
only
seed
treatment
uses
of
lindane
on
cereal
grains
(including
barley,
corn,
oats,
rye,
sorghum,
and
wheat
but
excluding
rice
and
wild
rice).
The
rows
corresponding
to
these
crops
are
shaded.]
Root
and
Tuber
Vegetables
Group
Beet,
sugar,
root
None
established
No
23
40431207
24
Radish,
root
None
established
No
25
40431207
24
Leaves
of
Root
and
Tuber
Vegetables
Group
Beet,
sugar,
tops
(leaves)
None
established
No
23
40431207
24
Radish,
tops
(leaves)
None
established
No
25
40431207
24
Bulb
Vegetables
(Allium
spp.)
Group
Onions
(dry
bulb)
1
No
23
Leafy
Vegetables
(Except
Brassica
Vegetables)
Group
Celery
(seed
treatment)
1
No
23
Lettuce
(seed
treatment)
3
No
26
41289407
Spinach
(seed
treatment)
1
No
26
40431207
24
Swiss
chard
(seed
treatment)
1
No
23
Brassica
(Cole)
Leafy
Vegetables
Group
Broccoli
(seed
treatment)
1
No
27
Brussels
sprouts
(seed
treatment)
1
No
27
Cabbage
(seed
treatment)
1
No
27
41289403
Cauliflower
(seed
treatment)
1
No
27
Table
A
(continued).
GLN:
Data
Requirements
Current
Tolerances,
ppm
[40
CFR
§180.133]
Must
Additional
Data
Be
Submitted?
References
1
(continued;
footnotes
follow)
32
Collards
(seed
treatment)
1
No
23
Kale
(seed
treatment)
1
No
23
Kohlrabi
(seed
treatment)
1
No
23
Mustard
greens
(seed
treatment)
1
No
23
40431207
24
Rape
greens
(seed
treatment)
None
established
No
23
Fruiting
Vegetables
(Except
Cucurbits)
Group
Eggplant
1
No
23
Pepper
1
No
23
Tomato
3
No
23
41699701
20
,
41861201
28
Cucurbit
Vegetables
Group
Cucumber
3
No
23
41289404
Melons
3
No
23
Pumpkin
3
No
23
Squash
3
No
23
Pome
Fruits
Group
Apple
1
No
23
41289401
Pear
1
No
23
Quince
1
No
23
Stone
Fruits
Group
Apricot
1
No
23
Table
A
(continued).
GLN:
Data
Requirements
Current
Tolerances,
ppm
[40
CFR
§180.133]
Must
Additional
Data
Be
Submitted?
References
1
(continued;
footnotes
follow)
33
Cherry
1
No
23
Nectarine
1
No
23
Peach
1
No
23
41289408
Plum(
freshprune)
1
No
23
Tree
Nuts
Group
Pecan
0.
01
No
23
41289601,
41421001
Cereal
Grains
Group
Barley
grain
(seed
treatment)
None
established
No
29
Corn
grain
(seed
treatment)
None
established
No
40431207
24
Oats
grain
(seed
treatment)
None
established
No
29
Rye
grain
(seed
treatment)
None
established
No
29
Sorghum
grain
(seed
treatment)
None
established
No
32
40431207
24
Wheat
grain
(seed
treatment)
None
established
No
29
40431207
24
,
44909901
14
Canola
grain
(seed
treatment)
None
established
Yes
30
44864401
31
,
45310501
31
Forage,
Fodder,
and
Straw
of
Cereal
Grains
Group
(Excluding
Rice
and
Wild
Rice)
Barley
hay
and
straw
(seed
treatment)
None
established
No
29
Corn
forage
and
stover
(seed
treatment)
None
established
No
40431207
24
Oats
forage,
hay,
and
straw
(seed
treatment)
None
established
No
29
Rye
forage
and
straw
(seed
treatment)
None
established
No
29
Table
A
(continued).
GLN:
Data
Requirements
Current
Tolerances,
ppm
[40
CFR
§180.133]
Must
Additional
Data
Be
Submitted?
References
1
(continued;
footnotes
follow)
34
Sorghum
forage
and
stover
(seed
treatment)
None
established
No
32
40431207
24
Wheat
forage,
hay,
and
straw
(seed
treatment)
None
established
No
29
40431207
24
,
44909901
14
Canola
forage,
hay,
and
straw
(seed
treatment)
None
established
Yes
30
44864401
31
,
45310501
31
Miscellaneous
Commodities
Asparagus
1
No
23
Avocado
1
No
23
Grape
1
No
23
41289405
Guava
1
No
23
Mango
1
No
23
Miscellaneous
crops
with
seed
treatments
only
None
established
No
23
40431207
24
Mushroom
3
No
23
Okra
1
No
23
Pineapple
1
No
23
Strawberry
1
No
23
Tobacco
None
established
No
23
41289409
860.1520:
Processed
Food/
Feed
Apple
None
established
No
23
41289402
Canola
None
established
Yes
18
44864401
31
,
45310501
31
Table
A
(continued).
GLN:
Data
Requirements
Current
Tolerances,
ppm
[40
CFR
§180.133]
Must
Additional
Data
Be
Submitted?
References
1
35
1.
Bolded
references
were
reviewed
in
the
Residue
Chemistry
Chapter
to
the
Lindane
Reregistration
Standard
dated
6/
7/
85
and
its
9/
5/
85
addendum.
Italicized
references
were
reviewed
in
the
Lindane
Product
and
Residue
Chemistry
Reregistration
Standard
Updates
(CB
No.
6961,
1/
31/
91,
E.
Zager).
All
other
references
were
reviewed
as
noted.
The
basic
registrants
are
supporting
only
seed
treatment
uses
of
lindane
on
cereal
grains
(including
barley,
corn,
oats,
rye,
sorghum,
and
wheat
but
excluding
rice
and
wild
rice).
The
rows
corresponding
to
these
crops
are
shaded.
2.
The
registrants
must
submit
a
formal
petition
for
the
establishment
of
tolerances
for
all
appropriate
RACs
being
supported
for
seed
treatment
uses.
The
petition
should
include
all
requisite
petition
sections
including
a
Section
B
specifying
the
maximum
use
rate
(in
terms
of
oz
ai/
100
lb
of
seeds
or
cwt)
and
information
pertaining
to
recommended
seeding
rate
per
acre
should
be
included
in
order
to
allow
the
Agency
to
calculate
rates
in
terms
of
lb
ai/
A.
In
addition,
the
registrants
should
formally
request
the
cancellation
of
all
Cereal
grains
None
established
Yes
33
Grape
None
established
No
23
41289406
Tomato
None
established
No
23
41861202
28
860.1480:
Meat,
Milk,
Poultry,
Eggs
Milk,
Fat,
Meat,
and
Meat
Byproducts
of
Cattle,
Goats,
Hogs,
Horses,
and
Sheep
7(
fat
ofmeat
from
cattle,
goats,
horses,
and
sheep);
4(
fat
ofmeat
from
hogs)
Reserved
40
00025685,
00045126,
00075989,
00088048,
00088165,
00089592,
00101478,
00104441,
00118722,
00118723,
00118724,
00118725,
00118739,
GS
00018,
GS
00021,
GS
00022,
GS
00023,
40660503
34
,
40660504
35
,
40660505
36
Eggs
and
the
Fat,
Meat,
and
Meat
Byproducts
of
Poultry
None
established
Reserved
40
40660501
37
,
44440604
16
860.1400:
Water,
Fish,
and
Irrigated
Crops
None
established
No
860.1460:
Food
Handling
None
established
No
860.1850:
Confined
Rotational
Crops
N/
A
No
38
41967301
39
860.1900:
Field
Rotational
Crops
None
established
Reserved
38
Table
A
(continued).
36
food/
feed
uses
except
seed
treatment
and
requests
that
all
labels
for
the
agricultural
use
of
formulated
lindane
be
revised
to
allow
only
seed
treatment
uses.
3.
A
new
plant
metabolism
study
reflecting
seed
treatment
are
required.
This
study
should
be
conducted
on
a
representative
cereal
grain
as
the
registrants
have
indicated
that
the
only
food/
feed
uses
they
are
supporting
are
for
seed
treatment
of
these
crops.
Crop
samples
should
be
harvested
at
the
appropriate
stage.
In
addition,
care
should
be
taken
to
insure
that
radioactivity
is
not
lost
during
analysis.
Identification
of
14
C
residues
should
also
be
confirmed
using
more
than
one
method,
or
by
GC/
MS.
4.
CB
No.
3267,
3/
24/
88,
G.
Otakie.
5.
DP
Barcode
D239699,
12/
16/
97,
S.
Funk.
6.
DP
Barcode
D240495,
12/
14/
99,
T.
Morton.
7.
The
qualitative
nature
of
the
residue
in
ruminants
and
poultry
is
adequately
understood.
The
results
of
the
ruminant
and
poultry
metabolism
studies
will
be
presented
to
the
HED
Metabolism
Assessment
Review
Committee
(MARC)
for
determination
of
terminal
residue
of
concern
in
eggs,
milk,
and
animal
tissues
when
an
acceptable
plant
metabolism
study
is
submitted.
If
the
HED
MARC
determines
that
lindane
is
the
only
residue
of
concern
requiring
regulation,
then
the
existing
storage
stability
data
for
livestock
commodities,
the
analytical
method
used
for
data
collection,
and
the
livestock
feeding
studies
will
be
upgraded
to
acceptable
status.
8.
CB
No.
3315,
3/
24/
88,
J.
Onley.
9.
CB
No.
3312,
3/
24/
88,
C.
Deyrup.
10.
DP
Barcode
D257805,
12/
14/
99,
T.
Morton.
11.
DP
Barcode
D271442
and
D274158,
4/
18/
01,
T.
Morton.
12.
Adequate
methods
are
available
for
determination
of
residues
of
lindane
per
se
in/
on
plant
and
animal
commodities.
However,
the
adequacy
of
the
available
analytical
methods
cannot
be
determined
until
the
registrants
submit
acceptable
plant
metabolism
studies
reflecting
seed
treatment,
and
the
HED
MARC
has
determined
the
total
toxic
residues
of
lindane
that
need
to
be
included
in
the
tolerance
expression.
The
registrants
are
reminded
that
radiovalidation
of
enforcement
method(
s)
is
a
reregistration
requirement;
representative
samples
from
the
requested
plant
metabolism
study
should
be
used
for
radiovalidation
and
analyzed
by
the
existing
or
proposed
enforcement
method(
s)
to
determine
whether
total
toxic
residues
are
extracted
from
weathered
samples.
13.
CB
No.
3257,
3/
24/
88,
N.
Dodd.
14.
DP
Barcode
D259318,
8/
30/
00,
T.
Morton.
15.
CB
No.
3261,
3/
24/
88,
N.
Dodd.
16.
DP
Barcode
D242510,
12/
14/
99,
T.
Morton.
17.
Should
the
HED
MARC
determine
that
lindane
metabolites
other
than
the
parent
should
be
regulated,
the
Agency
will
require
the
registrants
to
submit
additional
multiresidue
methods
test
data
for
the
metabolites
of
concern.
Table
A
(continued).
37
18.
Additional
storage
stability
data
(temperature
logs)
are
required
for
the
canola
field
trials
and
the
canola
processing
study.
Storage
stability
data
are
also
required
to
support
the
requested
corn
processing
study.
Additional
storage
stability
data
may
be
required
if
the
HED
MARC
determines
that
additional
lindane
metabolites
of
concern
need
to
be
included
in
the
tolerance
expression.
19.
CB
No.
3260,
3/
24/
88,
N.
Dodd.
20.
CB
No.
7470,
3/
29/
91,
R.
Perfetti.
21.
Assuming
that
lindane
per
se
is
the
terminal
residue
of
concern
in
animal
commodities,
adequate
storage
stability
data
are
available
to
support
the
storage
conditions
and
intervals
of
samples
collected
from
existing
ruminant
and
poultry
feeding
studies.
Additional
storage
stability
data
may
be
required
if
the
HED
MARC
determines
that
additional
lindane
metabolites
of
concern
need
to
be
included
in
the
tolerance
expression.
22.
CB
No.
4035,
8/
23/
88
and
8/
26/
88
(addendum),
S.
Willett.
23.
Because
no
registrants
have
committed
to
support
use(
s)
of
lindane
on
this
crop,
no
residue
data
are
required.
The
Agency
recommends
that
this
use
site
be
deleted
from
all
lindane
end
use
products.
The
Agency
also
recommends
the
revocation
of
existing
lindane
tolerances,
if
established,
on
the
RACs
of
crops
which
are
not
being
supported.
24.
CB
No.
3259,
3/
24/
88,
N.
Dodd.
25.
Because
no
registrants
have
committed
to
support
use(
s)
of
lindane
on
this
crop,
no
residue
data
are
required.
The
Agency
recommends
that
this
use
site
be
deleted
from
all
lindane
end
use
products.
The
Agency
also
recommends
the
revocation
of
existing
lindane
tolerances,
if
established,
on
the
RACs
of
crops
which
are
not
being
supported.
26.
Because
no
registrants
have
committed
to
support
use(
s)
of
lindane
on
this
crop,
no
residue
data
are
required.
The
Agency
recommends
that
this
use
site
be
deleted
from
all
lindane
end
use
products.
The
Agency
also
recommends
the
revocation
of
existing
lindane
tolerances,
if
established,
on
the
RACs
of
crops
which
are
not
being
supported.
27.
Because
no
registrants
have
committed
to
support
use(
s)
of
lindane
on
this
crop,
no
residue
data
are
required.
The
Agency
recommends
that
this
use
site
be
deleted
from
all
lindane
end
use
products.
The
Agency
also
recommends
the
revocation
of
existing
lindane
tolerances,
if
established,
on
the
RACs
of
crops
which
are
not
being
supported.
28.
CB
No.
8075,
DP
Barcode
D164898,
4/
8/
92,
R.
Perfetti.
29.
Assuming
that
lindane
per
se
is
the
terminal
residue
of
concern
in
plants,
the
available
residue
data,
reflecting
seed
treatment,
for
wheat
grain,
forage,
hay,
and
straw
may
be
translated
to
the
RACs
of
barley,
oats,
and
rye,
provided
the
registrants
propose
identical
use
patterns
and
tolerances.
The
registrants
may
propose
a
maximum
seed
treatment
rate
of
0.
052
oz
ai/
cwt
(or
330
ppm
lindane
on
the
seed)
on
small
cereal
grains
which
is
supported
by
adequate
residue
data.
30.
Assuming
that
lindane
per
se
is
the
terminal
residue
of
concern
in
plants,
two
additional
field
trials
are
required
for
canola.
31.
DP
Barcode
269388
and
D273830,
5/
10/
01,
T.
Morton.
Table
A
(continued).
38
32.
Assuming
that
lindane
per
se
is
the
terminal
residue
of
concern
in
plants,
the
available
seed
treatment
data
for
corn
may
be
translated
to
sorghum,
provided
the
registrants
propose
identical
use
patterns
and
tolerances.
33.
The
registrants
are
required
to
submit
processing
data
to
determine
whether
lindane
residues
of
concern
concentrate
in
the
processed
fractions
of
corn
following
seed
treatment.
34.
CB
No.
4036,
8/
31/
88,
M.
Kovacs.
35.
CB
No.
4038,
8/
29/
88,
S.
Willett.
36.
CB
No.
4037,
9/
20/
88,
M.
Kovacs.
37.
CB
No.
4034,
8/
31/
88,
G.
Otakie.
38.
For
the
purpose
of
reregistration,
the
Agency
will
not
require
a
new
confined
rotational
crop
study
provided
the
registrants
propose
a
30
day
plantback
interval
for
leafy
vegetables
and
a
12
month
plantback
interval
for
all
other
unregistered
crops
on
all
of
their
end
use
product
labels
for
lindane.
If
this
recommendation
is
not
acceptable
to
the
registrants,
then
limited
rotational
field
trial
data
are
required.
The
limited
field
trials
should
be
conducted
on
a
representative
crop
(as
defined
in
40
CFR
180.41)
at
two
sites
per
crop
for
the
following
three
crop
groups:
root
and
tuber
vegetables,
leafy
vegetables
and
small
grains
(wheat,
barley,
oats,
and
rye)
for
a
total
of
six
trials.
As
with
confined
studies
(OPPTS
860.1850),
soybeans
may
be
substituted
for
the
leafy
vegetable.
The
six
trials
should
be
conducted
on
crops
which
a
registrant
intends
to
have
as
rotational
crops
on
the
label.
In
addition,
some
of
the
six
trials
could
be
conducted
using
other
crops
that
are
typically
involved
in
crop
rotation
such
as
alfalfa
and
soybeans.
The
registrant
has
informed
the
Agency
they
will
propose
the
specified
plantback
intervals.
39.
DP
Barcodes
D172626
and
D198353,
8/
30/
00,
T.
Morton.
40.
The
nature
of
the
residue
in
plants
is
not
understood.
Upon
receipt
of
the
requested
plant
metabolism
data,
the
Agency
will:
(I)
determine
the
adequacy
of
established
tolerances
for
animal
commodities;
(ii)
calculate
the
expected
dietary
intake
for
beef
cattle,
dairy
cattle,
and
swine;
and
(iii)
reevaluate
the
need
for
additional
feeding
studies.
Assuming
that
lindane
per
se
is
the
only
residue
of
concern
in
animals,
acceptable
ruminant
and
poultry
feeding
studies
are
available.
39
TOLERANCE
REASSESSMENT
SUMMARY
Tolerances
for
residues
of
lindane
in/
on
raw
agricultural
and
animal
commodities
are
established
under
40
CFR
§180.133
and
expressed
in
terms
of
residues
of
lindane
per
se
[gamma
isomer
of
benzene
hexachloride].
The
residue
definition
for
lindane
is
misleading
and
should
be
amended
as
follows
to
harmonize
with
IUPAC
nomenclature:
gamma
isomer
of
1,
2,
3,
4,
5,
6hexachlorocyclohexane
Plant
commodity
tolerances
for
lindane
were
originally
established
based
on
registered
uses
which
included
preplant
soil
application,
foliar
applications,
and
seed
treatments.
Animal
commodity
tolerances
were
established
based
on
uses
which
included
direct
livestock
animal
treatment
as
well
as
animal
premise
treatment.
Refer
to
Table
B
for
a
list
of
established
lindane
tolerances.
The
only
food/
feed
use
of
lindane
which
is
being
supported
for
reregistration
is
seed
treatment
on
cereal
grains
(excluding
rice
and
wild
rice).
A
definitive
reassessment
of
the
currently
established
tolerances
for
lindane
cannot
be
made
at
this
time
due
to
major
deficiencies
in
the
residue
chemistry
database.
The
Agency
tentatively
concludes
that
no
changes
in
the
present
tolerance
expression
are
required
at
this
time
until
the
nature
of
the
residue
in
plants
and
animals
is
adequately
elucidated,
and
HED's
MARC
has
determined
the
terminal
residues
of
concern.
Because
of
the
Agency's
concerns
about
the
possibility
of
human
health
effects
due
to
dietary
exposure
to
lindane
and
the
lack
of
data
to
support
seed
treatment
uses,
no
additional
tolerances
other
than
those
required
to
support
the
basic
registrants'
proposed
seed
treatment
uses,
will
be
considered
until
the
data
gaps
identified
in
this
Residue
Chemistry
Chapter
are
fulfilled.
The
listing
of
lindane
tolerances
under
40
CFR
§180.133
should
be
subdivided
into
parts
(a),
(b),
(c),
and
(d).
Part
(a)
should
be
reserved
for
commodities
with
permanent
tolerances,
part
(b)
for
Section
18
emergency
exemptions,
part
©
for
tolerances
with
regional
registrations,
and
part
(d)
for
indirect
or
inadvertent
residues.
Tolerances
Listed
Under
40
CFR
§180.133:
Following
resolutions
of
residue
chemistry
data
deficiencies
specified
in
this
Residue
Chemistry
Science
Chapter,
a
statement
in
40
CFR
§180.133
should
be
added
to
specify
that
the
established
tolerances
result
from
seed
treatment
only.
The
established
tolerances
for
the
following
commodities
should
be
revoked
because
no
registrants
have
committed
to
support
their
uses:
apples,
apricots,
asparagus,
avocados,
broccoli,
Brussels
sprouts,
cabbage,
cauliflower,
celery,
cherry,
collards,
cucumbers,
eggplants,
grapes,
guavas,
kale,
kohlrabi,
lettuce,
mangoes,
melons,
mushrooms,
mustard
greens,
nectarines,
okra,
onions
(dry
bulb
only),
peaches,
pears,
pecans,
peppers,
pineapple,
plums
(fresh
prunes),
pumpkins,
quinces,
radish,
spinach,
squash,
strawberries,
summer
squash,
swiss
chard,
and
tomatoes.
40
Tolerances
To
Be
Proposed
Under
40
CFR
§180.133:
Tolerances
for
lindane
residues
of
concern
need
to
be
established
for:
barley,
grain;
barley,
hay;
barley,
straw;
corn,
grain;
corn,
forage;
corn,
stover;
oat,
grain;
oat,
forage;
oat,
hay;
oat,
straw;
rye,
grain;
rye,
forage;
rye,
straw;
sorghum,
grain;
sorghum,
forage;
sorghum,
stover;
wheat,
grain;
wheat,
forage;
wheat,
hay;
and
wheat,
straw
once
required
data
are
submitted.
In
addition,
the
need
for
tolerances
for
livestock
tissues,
milk,
poultry
tissues
and
eggs
will
be
reevaluated
once
additional
plant
metabolism
data
is
submitted.
Pending
Tolerance
Petitions:
In
1993,
CIEL
proposed
to
delete
all
food/
feed
uses
except
seed
treatment.
Concomitantly,
CIEL
proposed
to
establish
tolerances
of
0.1
ppm
for
residues
of
lindane
per
se
in/
on
several
RACs
as
a
result
of
seed
treatment.
In
an
initial
Agency
review
(DP
Barcode
D213401,
10/
31/
95,
S.
Funk)
of
available
residue
data
reflecting
seed
treatment,
the
Agency
concluded
that
the
proposed
tolerances
were
adequate
in
some
instances
and
inadequate
or
non
acceptable
in
others.
In
those
instances
where
the
proposed
tolerances
were
deemed
inadequate,
the
reviewer
proposed
values
that
HED
would
consider
as
appropriate.
In
1998,
CIEL
submitted
a
petition,
PP#
9F05057,
for
the
establishment
of
time
limited
tolerances
for
residues
of
lindane
per
se
in/
on
several
commodities
resulting
from
seed
treatment.
The
Agency
review
(DP
Barcodes
D254236,
8/
30/
00,
T.
Morton)
of
these
tolerance
proposals
concluded
that
tolerances
could
not
be
established
until
an
adequate
plant
metabolism
study
was
submitted.
The
registrants
have
also
submitted
PP#
9F6022,
(D269388,
T.
Morton,
5/
10/
01)
for
the
establishment
of
tolerances
on
lindane
per
se
in/
on
canola
for
which
seed
treatment
is
being
proposed.
Tolerances
cannot
be
established
or
reassessed
until
an
adequate
plant
metabolism
study
is
submitted.
41
Table
B.
Tolerance
Reassessment
Summary
for
Lindane.
Commodity
Tolerance
Listed
Under
40
CFR
(ppm)
Reassessed
Tolerance
(ppm)
Comment
[Correct
Commodity
Definition]
Tolerance
Listed
Under
40
CFR
§180.133
Apples
1
Revoke
Not
being
supported
for
reregistration.
Apricots
1
Revoke
Not
being
supported
for
reregistration.
Asparagus
1
Revoke
Not
being
supported
for
reregistration.
Avocados
1
Revoke
Not
being
supported
for
reregistration.
Broccoli
1
Revoke
Not
being
supported
for
reregistration.
Brussels
sprouts
1
Revoke
Not
being
supported
for
reregistration.
Cabbage
1
Revoke
Not
being
supported
for
reregistration.
Cauliflower
1
Revoke
Not
being
supported
for
reregistration.
Lettuce
3
Revoke
Not
being
supported
for
reregistration.
Spinach
1
Revoke
Not
being
supported
for
reregistration.
Celery
1
Revoke
Not
being
supported
for
reregistration.
Collards
1
Revoke
Not
being
supported
for
reregistration.
Kale
1
Revoke
Not
being
supported
for
reregistration.
Kohlrabi
1
Revoke
Not
being
supported
for
reregistration.
Mustard
greens
1
Revoke
Not
being
supported
for
reregistration.
Swiss
chard
1
Revoke
Not
being
supported
for
reregistration.
Cherry
1
Revoke
Not
being
supported
for
reregistration.
Cucumbers
3
Revoke
Not
being
supported
for
reregistration.
Eggplants
1
Revoke
Not
being
supported
for
reregistration.
Fat
of
meat
from
cattle,
goats,
horses,
and
sheep
7
To
be
determined
(TBD)
The
Agency
will
re
calculate
the
maximum
theoretical
dietary
burden
for
livestock
animals
and
re
assess
the
adequacy
of
the
available
animal
feeding
studies
when
the
requested
residue
data
for
livestock
feed
items
have
been
received
and
evaluated.
Fat
ofmeat
from
hogs
4
Grapes
1
Revoke
Not
being
supported
for
reregistration.
Guavas
1
Revoke
Not
being
supported
for
reregistration.
Mangoes
1
Revoke
Not
being
supported
for
reregistration.
Melons
3
Revoke
Not
being
supported
for
reregistration.
Mushrooms
3
Revoke
Not
being
supported
for
reregistration.
Nectarines
1
Revoke
Not
being
supported
for
reregistration.
Okra
1
Revoke
Not
being
supported
for
reregistration.
Onions
(dry
bulb
only)
1
Revoke
Not
being
supported
for
reregistration.
Peaches
1
Revoke
Not
being
supported
for
reregistration.
Pears
1
Revoke
Not
being
supported
for
reregistration.
Pecans
0.01
Revoke
Not
being
supported
for
reregistration.
Peppers
1
Revoke
Not
being
supported
for
reregistration.
Pineapple
1
Revoke
Not
being
supported
for
reregistration.
Table
B
(continued).
Commodity
Tolerance
Listed
Under
40
CFR
(ppm)
Reassessed
Tolerance
(ppm)
Comment
[Correct
Commodity
Definition]
42
Plums
(fresh
prunes)
1
Revoke
Not
being
supported
for
reregistration.
Pumpkins
3
Revoke
Not
being
supported
for
reregistration.
Quinces
1
Revoke
Not
being
supported
for
reregistration.
Squash
3
Revoke
Not
being
supported
for
reregistration.
Strawberries
1
Revoke
Not
being
supported
for
reregistration.
Summer
squash
3
Revoke
Not
being
supported
for
reregistration.
Tomatoes
3
Revoke
Not
being
supported
for
reregistration.
Tolerance
To
Be
Proposed
Under
40
CFR
§180.133
Barley,
grain
None
established
TBD
A
nature
of
the
residue
study
for
lindane
residues
resulting
from
seed
treatment
application
to
a
cereal
grain
is
required.
Barley,
hay
TBD
Barley,
straw
TBD
Canola,
seed
TBD
Corn,
grain
TBD
Corn,
forage
TBD
Corn,
stover
TBD
Oat,
grain
TBD
Oat,
forage
TBD
Oat,
hay
TBD
Oat,
straw
TBD
Rape
greens
TBD
Rye,
grain
TBD
Rye,
forage
TBD
Rye,
straw
TBD
Sorghum,
grain
TBD
Sorghum,
forage
TBD
Sorghum,
stover
TBD
Wheat,
grain
TBD
Wheat,
forage
TBD
Wheat,
hay
TBD
Wheat,
straw
TBD
TBD
=
To
be
determined.
43
CODEX
HARMONIZATION
The
Codex
Alimentarius
Commission
has
established
several
maximum
residue
limits
(MRLs)
for
lindane
in/
on
various
plant
and
animal
commodities.
The
Codex
MRLs
are
expressed
in
terms
of
gamma
HCH
(fat
soluble).
With
respect
to
tolerance
expression,
the
Codex
MRL
and
U.
S.
tolerance
for
lindane
are
presently
in
harmony.
However,
the
nature
of
the
residue
in
plants
and
ruminants
remains
inadequately
understood,
and
the
HED's
MARC
may
determine
that
additional
lindane
metabolites
should
be
included
in
the
U.
S.
tolerance
expression.
A
numerical
comparison
of
the
Codex
MRLs
and
the
corresponding
reassessed
U.
S.
tolerances
resulting
from
seed
treatment
is
presented
in
Table
C.
The
established
Codex
MRLs
and
the
recommended
U.
S.
tolerances
for
Brussels
sprouts,
cabbage
(Savoy),
cabbages
(head),
cereal
grains,
lettuce
(head),
and
radish
are
not
in
harmony
presumably
because
of
differences
in
good
agricultural
practices.
Attempts
to
harmonize
residue
limits
in
animal
commodities
cannot
be
made
at
this
time
because
of
several
residue
chemistry
data
gaps.
44
(continued
next
page).
Table
C.
Codex
MRLs
and
applicable
U.
S.
tolerances
for
lindane.
Recommendations
are
based
on
conclusions
following
reassessment
of
U.
S.
tolerances
(see
Table
B).
Codex
Reassessed
U.
S.
Tolerance,
ppm
1
Codex
Comments
Commodity,
As
Defined
MRL
in
mg/
kg
(Step)
Apple
0.
5
(CXL)
Revoke
Not
being
supported
for
reregistration.
Beans
(dry)
1
(CXL)
2
None
established
Not
being
supported
for
reregistration.
Brussels
sprouts
0.
5
(CXL)
Revoke
Not
being
supported
for
reregistration.
Cabbage,
Savoy
0.5
(CXL)
Revoke
Not
being
supported
for
reregistration.
Cabbages,
Head
0.5
(CXL)
Revoke
Not
being
supported
for
reregistration.
Cacao
beans
1
(CXL)
None
established
Not
being
supported
for
reregistration.
Carrot
0.
2
(CXL)
None
established
Not
being
supported
for
reregistration.
Cauliflower
0.
5
(CXL)
Revoke
Not
being
supported
for
reregistration.
Cereal
grains
0.
5
(CXL)
2
TBD
for
the
grains
of
barley,
oats,
rye,
and
wheat
Cherries
0.5
(CXL)
Revoke
Not
being
supported
for
reregistration.
Cocoa
butter
1
(CXL)
None
established
Not
being
supported
for
reregistration.
Cocoa
mass
1
(CXL)
None
established
Not
being
supported
for
reregistration.
Cranberry
3
(CXL)
None
established
Not
being
supported
for
reregistration.
Currant,
Red,
White
0.5
(CXL)
None
established
Not
being
supported
for
reregistration.
Eggs
0.1
(CXL)
None
established
Endive
2
(CXL)
None
established
Not
being
supported
for
reregistration.
Grapes
0.5
(CXL)
Revoke
Not
being
supported
for
reregistration.
Kohlrabi
1
(CXL)
Revoke
Not
being
supported
for
reregistration
Lettuce,
Head
2
(CXL)
Revoke
Not
being
supported
for
reregistration.
Meat
of
cattle,
pigs,
and
sheep
2
(CXL)
To
be
determined
(TBD)
Milks
0.
1
(CXL)
None
established
Pear
0.5
(CXL)
Revoke
Not
being
supported
for
reregistration.
Peas
(pods
and
succulent
=
immature
seeds)
0.1
(CXL)
None
established
Not
being
supported
for
reregistration.
Plums
(including
prunes)
0.
5
(CXL)
Revoke
Not
being
supported
for
reregistration.
Potato
0.05
(CXL)
None
established
Not
being
supported
for
reregistration.
Poultry
meat
0.
7
(CXL)
None
established
Radish
1
(CXL)
Revoke
Not
being
supported
for
reregistration.
Rape
seed
0.05
(CXL)
None
established
Spinach
2
(CXL)
Revoke
Not
being
supported
for
reregistration.
Strawberry
3
(CXL)
Revoke
Not
being
supported
for
reregistration.
Codex
Reassessed
U.
S.
Tolerance,
ppm
1
Codex
Comments
Commodity,
As
Defined
MRL
in
mg/
kg
(Step)
45
Sugar
beet
0.1
(CXL)
None
established
Not
being
supported
for
reregistration.
Sugar
beet
leaves
or
tops
0.1
CXL)
None
established
Not
being
supported
for
reregistration.
Tomato
2
(CXL)
Revoke
Not
being
supported
for
reregistration.
1
Reassessed
U.
S.
tolerances
pending
compliance
by
the
registrants
with
the
recommendations
specified
in
"GLN
860.1200:
Directions
for
Use"
section
of
this
Chapter.
2
Postharvest
treatment
of
the
commodity.
TBD
=
To
be
determined.
DIETARY
EXPOSURE
ASSESSMENT
Anticipated
residues
of
lindane
were
recently
determined
by
HED
(DP
Barcode
D279260,
T.
Morton,
12/
4/
01)
using
data
from
available
plant
and
animal
metabolism
studies
along
with
animal
feeding
studies.
46
AGENCY
MEMORANDA
RELEVANT
TO
REREGISTRATION
CB
No.:
3257
Subject:
ID
No.
359
686.
Lindane
Registration
Standard
Followup.
Analytical
Methods
for
Plants
From:
N.
Dodd
To:
A.
Rispin,
G.
LaRocca,
and
E.
Budd
Dated:
3/
24/
88
MRID(
s):
40431202
and
40431206
CB
No.:
3259
Subject:
ID
No.
359
686.
Lindane
Registration
Standard
Followup
Residues
From
Seed
Treatment
From:
N.
Dodd
To:
A.
Rispin,
G.
LaRocca,
and
E.
Budd
Dated:
3/
24/
88
MRID(
s):
40431207
CB
No:
3260
Subject:
Lindane
Registration
Standard
Follow
up.
Storage
stability.
From:
N.
Dodd
To:
A.
Rispin,
G.
LaRocca,
and
E.
Budd
Dated:
3/
24/
88
MRIDs:
40431203
and
40431205
CB
No:
3261
Subject:
Lindane
Registration
Standard
Follow
up
Analytical
Methods
for
Animal
Tissues,
Eggs,
and
Milk.
From:
N.
Dodd
To:
A.
Rispin,
G.
LaRocca,
and
E.
Budd
Dated:
3/
24/
88
MRID:
40431208
CB
No.
3267
Subject:
Partial
Response
(November
10,
1987)
by
Centre
International
d'Etudes
du
Lindane
(CIEL)
to
Data
Gap
171
4
(Nature
of
the
Residue
in
Plants
as
Identified
in
the
Residue
Chemistry
Chapter
of
the
September
30,
1985
Lindane
Registration
Standard
From:
G.
Otakie
To:
A.
Rispin,
G.
LaRocca,
and
E.
Budd
Dated:
3/
24/
88
MRID(
s):
40410902,
40431201,
and
40431204
CB
No:
3312
Subject:
Partial
Response
(7/
21/
87)
by
Centre
International
d'Etudes
du
Lindane
(CIEL)
to
Data
Gap
171
4
(Nature
of
the
Residue
in
Livestock
Ruminants)
as
Identified
in
the
Residue
Chemistry
Chapter
of
the
September
30,
1985
Lindane
Registration
Standard.
From:
C.
Deyrup
To:
A.
Rispin,
G.
LaRocca,
and
E.
Budd
Dated:
3/
24/
88
MRID:
40271302
47
DEB
No.
3315
Subject:
Partial
Response
(July
15,
1987)
by
Centre
International
d'Etudes
du
Lindane
(CIEL)
to
Data
Gap
171
4
(Nature
of
the
Residue
in
Livestock
Poultry)
as
Identified
in
the
Residue
Chemistry
Chapter
of
the
September
30,
1985
Lindane
Registration
Standard
From:
J.
Onley
To:
A.
Rispin,
G.
LaRocca,
and
E.
Budd
Dated:
3/
24/
88
MRID(
s):
40271301
CB
No:
4035
Subject:
ID
No.
52904
C.
Lindane
Registration
Standard
Followup.
Storage
Stability
Data.
From:
S.
Willett
To:
R.
Engler,
G.
LaRocca,
and
E.
Budd
Dated:
8/
23/
88
and
8/
26/
88
(addendum)
MRID:
40660502
CB
No:
4034
Subject:
Partial
Response
(June
9,
1988)
by
Centre
International
d'Etudes
du
Lindane
(CIEL)
to
Data
Gap
Section
171
4
(Magnitude
of
the
Residue
in
Poultry
and
Eggs)
as
Identified
in
the
Residue
Chemistry
Chapter
of
the
September
30,
1985
Lindane
Registration
Standard.
From:
G.
Otakie
To:
R.
Engler,
G.
LaRocca,
andE.
Budd
Dated:
8/
31/
88
MRID:
40660501
CB
No.:
4038
Subject:
ID
No.
52904
C.
Lindane
Registration
Standard
Followup.
Residues
in
Swine
From:
S.
Willett
To:
R.
Engler,
G.
LaRocca,
andE.
Budd
Dated:
8/
29/
88
MRID(
s):
40660504
CB
No.:
4036
Subject:
Partial
Response
(April
7,
1988)
by
Centre
International
d'Etudes
du
Lindane
(CIEL)
to
Data
Gap
Section
171
4
[Magnitude
of
Residue
in
Animals
(Sheep)]
as
Identified
in
the
Residue
Chemistry
Chapter
of
the
September
30,
1985
Lindane
Registration
Standard.
From:
M.
Kovacs
To:
R.
Engler,
G.
LaRocca,
andE.
Budd
Dated:
8/
31/
88
MRID(
s):
40660503
CB
No.:
4037
Subject:
Partial
Response
(December
15,
1987)
by
Centre
International
d'Etudes
du
Lindane
(CIEL)
to
Data
Gap
171
4
[Magnitude
of
Residue
in
Animals
(Dairy
Cattle
Meat
and
Milk)]
as
Identified
in
the
Residue
Chemistry
Chapter
of
the
September
30,
1985
Lindane
Registration
Standard
From:
M.
Kovacs
To:
R.
Engler,
G.
LaRocca,
E.
Budd
Dated:
9/
20/
88
MRID(
s):
40660505
48
CB
No.:
7470
Subject:
Rhone
Poulenc
AG
Company:
Response
to
the
Lindane
Reregistration
Standard:
Crop
field
Trials
and
Storage
Stability
Data
From:
R.
Perfetti
To:
R.
Engler
and
L.
Rossi
Dated:
3/
29/
91
MRID:
41699701
CB
No.
8075
DP
Barcode:
D164898
Subject:
CIEL:
Response
to
the
Lindane
Reregistration
Standard:
Residue
and
Processing
Data
From:
R.
Perfetti
To:
W.
Burnam
and
L.
Rossi
Dated:
4/
8/
92
MRID:
41861201
and
41861202
CB
No.
15325
DP
Barcode:
D213401
Subject:
Lindane
(Case
0315,
Chemical
009001,
List
A).
Seed
Treatment
Uses.
From:
S.
Funk
To:
L.
Schnaubelt/
R.
Richards
Dated:
10/
31/
95
MRID:
None
DP
Barcode:
D239699
Subject:
Lindane
(Chemical
009001,
List
A):
CIEL
Submissions
to
Upgrade
Plant
Analytical
Method,
Nature
of
the
Residue
in/
on
Cucumbers,
Nature
of
the
Residue
in/
on
Apples.
Time
Extension
Request
for
Ruminant
Feeding
Study,
Ruminant
Commodity
Storage
Stability
Study,
and
Ruminant
Commodity
Analytical
Method
Study.
From:
S.
Funk
To:
S.
Jennings/
W.
Waldrop
Dated:
12/
16/
97
MRID(
s):
44383001
through
44383004
DP
Barcode:
D240495
Subject:
Lindane
(009001):
Nature
of
the
Residue
in
Spinach
and
Poultry
(GLN
860.1300).
From:
T.
Morton
To:
M.
McDavit/
B.
Shackleford
Dated:
12/
14/
99
MRID(
s):
44405403
and
44405404
DP
Barcode:
D242510
Subject:
Lindane
(009001):
Nature
of
the
Residue
in
Plants
and
Animals
(GLN
860.1300),
Storage
Stability
(GLN
860.1380),
Residue
Analytical
Method
(GLN
860.1340),
and
Meat,
Milk,
Poultry,
Eggs
(GLN
860.1480).
From:
T.
Morton
To:
M.
McDavit/
B.
Shackleford
Dated:
12/
14/
99
MRID(
s):
44440601,
44440602,
44440603,
and
44440604.
49
DP
Barcode:
D257805
Subject:
Lindane
(009001):
Nature
of
the
Residue
in
Livestock
(GLN
860.1300),
Residue
Analytical
Method
(GLN
860.1340),
and
Storage
Stability
(GLN
860.1380).
From:
T.
Morton
To:
M.
McDavit/
B.
Shackleford
Dated:
12/
14/
99
MRID(
s):
44867104,
44867105,
and
44867106
DP
Barcode:
D259318
Subject:
Lindane
(009001):
Magnitude
of
the
Residue
in/
on
Wheat
From:
T.
Morton
To:
M.
Howard/
B.
Shackleford
Dated:
8/
30/
00
MRID(
s):
44909901
DP
Barcode:
D254236
and
D265919
Subject:
PP#
9F05057.
Lindane
(009001):
Time
Limited
Tolerances
for
Various
Crops.
From:
T.
Morton
To:
M.
Howard/
B.
Shackleford
Dated:
8/
30/
00
MRID(
s):
None
DP
Barcode:
D172626
and
D198353
Subject:
Lindane:
Confined
Rotational
Crop
Study.
From:
T.
Morton
To:
M.
Howard/
B.
Shackleford
Dated:
8/
30/
00
MRID(
s):
41967301
DP
Barcode:
D269094
Subject:
Lindane
(009001):
Waiver
Request
for
Nature
of
the
Residue
in
Plants
Grown
From
Seed
Treated
With
Lindane
(GLN
860.1300).
From:
T.
Morton
To:
M.
Howard/
B.
Shackleford
Dated:
1/
9/
01
MRID(
s):
None
DP
Barcode:
D272625
Subject:
Lindane
(009001):
Clarification
on
Waiver
Request
for
Nature
of
the
Residue
in
Plants
Grown
From
Seed
Treated
With
Lindane
(GLN
860.1300).
From:
T.
Morton
To:
M.
Howard/
B.
Shackleford
Dated:
2/
13/
01
MRID(
s):
None
DP
Barcode:
D243547
Subject:
Lindane
(009001):
Question
on
Applicability
of
Seed
Treatment
Data
for
Pre
Plant
Soil
Treatment
Uses.
From:
T.
Morton
To:
M.
Howard/
B.
Shackleford
Dated:
2/
28/
01
MRID(
s):
None
50
DP
Barcode:
D244798
Subject:
Lindane
(009001):
Status
on
Residue
Chemistry
Requirements
for
Lindane
Seed
Treatment
Uses.
From:
T.
Morton
To:
M.
Howard/
B.
Shackleford
Dated:
3/
13/
01
MRID(
s):
None
DP
Barcode:
D258079
Subject:
Lindane
(009001):
Magnitude
of
the
Residue
in
Meat
and
Milk
of
Dairy
Cattle
(GLN
860.1480).
From:
T.
Morton
To:
M.
Howard/
B.
Shackleford
Dated:
3/
13/
01
MRID(
s):
44877501
DP
Barcode:
D269388
and
D273830
Subject:
PP#
9F6022
Lindane
(009001):
Lindane
in/
on
Canola.
From:
T.
Morton
To:
M.
Howard/
B.
Shackleford
Dated:
5/
10/
01
MRID(
s):
44864401
and
45310501
DP
Barcode:
D271442
and
D274158
Subject:
Lindane:
Nature
of
the
Residue
in
Livestock.
From:
T.
Morton
To:
M.
Howard/
B.
Shackleford
Dated:
4/
18/
01
MRID(
s):
45224101,
45224102,
45277201
DP
Barcode:
D274313
Subject:
Lindane
(009001):
Magnitude
of
the
Residue
in
Wheat.
From:
T.
Morton
To:
M.
Howard/
B.
Shackleford
Dated:
5/
10/
01
MRID(
s):
45330301
MASTER
RECORD
IDENTIFICATION
NUMBERS
References
Used
To
Support
Reregistration
00025685
Williams,
S.;
Mills,
P.
A.;
McDowell,
R.
E.
(1964)
Residues
in
milk
of
cows
fed
rations
containing
low
concentrations
of
five
Chlorinated
hydrocarbon
pesticides.
Journal
of
the
Association
of
Official
Analytical
Chemists
47(
6):
1124
1128.
(unpublished
submission
received
Nov
5,
1970
under
1F1060;
submitted
by
Velsicol
Chemical
Corp.,
Chicago,
Ill.;
CDL:
099195
AK)
00025690
Cummings,
J.
G.;
Eidelman,
M.;
Turner,
V.;
et
al.
(1967)
Residues
in
poultry
tissues
from
low
level
feeding
of
five
Chlorinated
hydrocarbon
insecticides
to
hens.
Journal
of
the
Association
of
Official
Analytical
Chemists
50(
2):
418
425.
(unpublished
submission
received
Nov
5,
1970
under
1F1060;
submitted
by
Velsicol
Chemical
Corp.,
Chicago,
Ill.;
CDL:
099195
AQ)
00025707
Hill,
K.
R.
(1970)
Pesticide
residues:
IUPAC
commission
on
terminal
residues.
Journal
of
the
Association
of
Official
Analytical
Chemists
53(
5):
987
1003.
(unpublished
submission
received
Nov
5,
1970
under
1F1060;
submitted
by
Velsicol
Chemical
Corp.,
Chicago,
Ill.;
CDL:
099195
BH)
51
00032233
Dionne,
E.;
Cary,
G.
A.;
Sleight,
B.
H.,
III
(1980)
Analytical
Procedure
for
the
Determination
of
Pesticides
and
PCB
in
Brine
Shrimp
Tissue.
(Unpublished
study
received
Feb
19,
1980
under
677
313;
prepared
by
EG&
G,
Bionomics,
submitted
by
Diamond
Shamrock
Agricultural
Chemicals,
Cleveland,
Ohio;
CDL:
099247
K)
00045126
Claborn,
H.
V.;
Radeleff,
R.
D.;
Bushland,
R.
C.
(1960)
Pesticide
Residues
in
Meat
and
Milk:
A
Research
Report.
(U.
S.
Agricultural
Research
Service,
Entomology
Research,
Div.
And
Animal
Disease
and
Parasite
Research
Div.,
unpublished
study;
CDL:
093429
S)
00060143
Saha,
J.
G.
(1969)
Letter
sent
to
P.
E.
Porter
dated
Mar
10,
1969
[Metabolism
of
Lindane
14C
by
wheat
plants].
(Canada,
Dept.
of
Agriculture,
Research
Branch,
unpublished
study;
CDL:
091355
S)
00060150
Lichtenstein,
E.
P.;
Fuhremann,
T.
W.;
Scopes,
N.
E.
A.;
et
al.
(1967)
Translocation
of
insecticides
from
soils
into
pea
plants:
Effects
of
the
detergent
LAS
on
translocation
and
plant
growth.
Journal
of
Agricultural
and
Food
Chemistry
15(
5):
864
869.
(unpublished
submission
received
Apr
5,
1969
under
9F0785;
submitted
by
Shell
Chemical
Co.,
Washington,
D.
C.;
CDL:
091355
Z)
00075989
Chevron
Chemical
Company
(1949)
Milk
Contamination
Studies.
(Unpublished
study
received
Jul
24,
1952
under
239
399;
CDL:
231161
B)
00088048
Gyrisco,
G.
G.;
Muka,
A.
A.
comps.
(1951)
Report
on
a
Preliminary
Study
on
the
Effects
of
Feeding
Insecticide
Treated
Alfalfa
Hay
to
Dairy
Cattle.
(Unpublished
study
received
Feb
21,
1955
under
PP0007;
prepared
by
G.
L.
F.
Soil
Building
Service
and
Cornell
Univ.,
Depts.
of
Entomology,
Animal
Husbandry
and
Dairy
Industry,
submitted
by
Shell
Chemical
Corp.,
New
York,
N.
Y.;
CDL:
090081
U)
00088165
National
Agricultural
Chemicals
Association
(1955?)
Supplementary
Petition
for
Lindane
Residue
Tolerance.
(Unpublished
study
received
Jan
25,
1956
under
PP0058;
CDL:
090056
A)
00089592
California
Spray
Chemical
Corporation
(1959)
Residues
of
Lindane
on
Raw
Agricultural
Commodities.
(Compilation;
unpublished
study
received
Apr
27,
1959
under
PP0190;
CDL:
090218
B)
00099909
Shell
Development
Co.
(1964)
Determination
of
Chlorinated
Pesticide
Residues
in
Water,
Soils,
Crops
and
Animal
Products:
GLC
Electron
Capture
Method:
Analytical
Method
MMS
43/
64.
(Unpublished
study
received
Nov.
9,
1964
under
unknown
administrative
number;
CDL:
129668
A)
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Tissue
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Tissue
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Landis
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Michigan,
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Pennsylvania,
North
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Field
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Michigan,
North
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Raw
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Field
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New
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Florida,
Georgia,
Texas,
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Landis
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20%
EC:
Raw
Agricultural
Commodity
Field
Residue
Protocol
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Grapes
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California,
Michigan,
New
York,
and
Washington:
Lab
Project
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6237/
116G.
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333
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Landis
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20%
EC:
Processed
Commodity
Field
Residue
Protocol
on
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California,
New
York,
and
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Lab
Project
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6237/
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Landis
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Lindane
25%
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F:
Raw
Agricultural
Commodity
Field
Residue
Protocol
on
Lettuce
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California,
Texas,
New
York,
and
New
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Lab
Project
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6237/
116L.
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study
prepared
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Hazleton
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471
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41289408
Landis
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Lindane
25%
WP:
Raw
Agricultural
Commodity
Field
Residue
Protocol
on
Peaches
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California,
Michigan,
Washington,
Pennsylvania,
and
Georgia:
Lab
Project
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HLA/
6237/
116P.
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prepared
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345
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Landis
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Lindane
20%
EC:
Raw
Agricultural
Commodity
Field
Residue
Protocol
on
Tobacco
in
Virginia
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Georgia:
Lab.
Project
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6237/
116P.
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prepared
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Hazleton
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237
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Landis
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Lindane
20%
EC:
Raw
Agricultural
Commodity
Field
Residue
Protocol
on
Pecans
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Louisiana,
Texas,
and
Oklahoma:
Lab
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Lindane
20
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Raw
Agricultural
Commodity
Field
Residue
Protocol
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Pecans
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Lab
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116
PC.
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153
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Landis
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Lindane
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Raw
Agricultural
Commodity
Field
Residue
on
Tomatoes
in
Florida,
Pennsylvania,
California,
New
Jersey,
Indiana,
Michigan,
and
South
Carolina:
Lab
Project
Number:
HLA
6237
116PT:
W714
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04
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Unpublished
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Lindane
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40%
F:
Processed
Commodity
Field
Residue
Protocol
on
Tomatoes
in
California,
New
Jersey,
Pennsylvania,
and
Michigan:
Lab
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116PT:
1717
89
44
04
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08:
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89
44
04
15B
04.
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prepared
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Lindane
20%
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Processed
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Lab
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44
01
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01:
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EF
88
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ABC
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Pan
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Curry,
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Metabolism
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14)
Lindane
in/
on
Apple
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and
Fruit
After
Treatment
With
(carbon
14)
Lindane
25%
EC:
Supplement:
Lab
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prepared
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Rhone
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40
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44383002
Curry,
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Insecticides:
Lindane(
carbon
14)
Metabolism
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Following
Post
Emergence
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Lab
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86/
004/
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68
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Brookman,
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Insecticides:
Lindane:
Analytical
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Determination
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Supplement:
Lab
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D.
AG
568.
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prepared
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11
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44383004
Curry,
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Brookman,
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Insecticides:
Lindane:
Analytical
Procedure
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Determination
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in
Cucumber:
Supplement:
Lab
Project
Number:
D.
AG
568.
Unpublished
study
prepared
by
May
&
Baker
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11
p.
44405403
Curry,
K.;
Brookman,
D.
(1997)
Insecticides:
Lindane(
carbon
14)
Metabolism
in
Spinach
Plants
Following
Post
Emergence
Application:
Supplement
Report:
Lab
Project
Number:
5739:
STUDY/
EC/
86/
001/
01:
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EC/
86/
001/
02.
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prepared
by
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53
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44405404
Curry,
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Brookman,
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(1997)
Determining
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Fed
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Hens:
Supplement
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Lab
Project
Number:
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study
prepared
by
Technology
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308
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55
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Insecticides:
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Unpublished
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Centre
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42
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44440602
Curry,
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Insecticides:
Lindane:
Freezer
Storage
Stability
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Cucumber
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Supplement:
Lab
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Unpublished
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prepared
by
Technology
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21
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44440603
Curry,
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Brookman,
D.
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Freezer
Storage
Stability
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Lindane
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Animal
Tissues,
Eggs
and
Milk:
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Unpublished
study
prepared
by
Technology
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Group,
Inc.
28
p.
44440604
Curry,
K.;
Brookman,
D.
(1997)
Freezer
Storage
Stability
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Lindane
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Animal
Tissues,
Eggs
and
Milk:
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Unpublished
study
prepared
by
Technology
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28
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44864401
Willard,
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Magnitude
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Lindane
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Canola
Raw
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Agricultural
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Unpublished
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American
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134
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44867104
Willems,
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Fate
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study
prepared
by
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BV.
211
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44867105
Curry,
K.;
Hemingway,
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Brookman,
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(1999)
Lindane:
Analytical
Method
for
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Residues
in
Animal
Tissues
and
Milk:
Supplement
Response
to
DER:
Lab
Project
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CIEL6/
993.
Unpublished
study
prepared
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Technology
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Group,
Inc.
48
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44867106
Curry,
K.;
Hemingway,
R.;
Brookman,
D.
(1999)
Freezer
Storage
Stability
of
Lindane
in
Animal
Tissues,
Eggs
and
Milk
Response
to
DER
and
Proposal
for
Study
Upgrade:
Supplement
to
MRID
406605
02:
Lab
Project
Number:
CIEL6/
99
2.
Unpublished
study
prepared
by
Technology
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Group,
Inc.
18
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44877501
Hemingway,
R.,
Curry,
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Brookman,
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Lindane:
Tissue
and
Milk
Residue
Study
in
Dairy
Cows
Response
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DER
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Proposal
for
Study
Upgrade,
Supplement
to
MRID
40660505.
A
supplemental
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prepared
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CIEL.
40
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Willard,
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Magnitude
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Residue
of
Lindane
in
Wheat
Raw
Agricultural
Commodities
Following
Seed
Treatment:
Lab
Project
Number:
AA980775:
AA970775:
AA970775.IA1.
Unpublished
study
prepared
by
American
Agricultural
Services,
Inc.
247
p.
45224101
Pluijmen,
M
and
Willems,
H.
(2000)
Fate
of
Orally
Administered
14
C
Lindane
in
the
Lactating
Goat:
Report
Amendment
01;
NOTOX
Project
Number
212761.
Unpublished
study
prepared
by
NOTOX.
14
p.
45224102
Stewart,
R.
(2000)
Fate
of
Orally
Administered
14
C
Lindane
in
the
Lactating
Goat:
Unaudited
Draft
Report.
Unpublished
study
prepared
by
Huntingdon
Life
Sciences.
10
p.
45277201
Aikens,
P.
(2000)
Investigations
Into
The
Identity
Of
A
Radioactive
Metabolite
Detected
In
The
Liver
Of
A
Goat
Dosed
With
14
C
Lindane:
Project
Number
SCI/
056.
Unpublished
study
prepared
by
Huntingdon
Life
Sciences
Ltd.
36
p.
45310501
Willard,
T.
(2000)
Magnitude
of
the
Residue
of
Lindane
in
Canola
Raw
and
Processed
Agricultural
Commodities
Following
Seed
Treatment
with
Premeire
Plus:
Lab
Project
Number:
AA980775.
Unpublished
study
prepared
by
American
Agricultural
Services,
Inc.
151
p.
45330301
Willard,
T.
(2001)
Magnitude
of
the
Residue
of
Lindane
in
Wheat
Raw
Agricultural
Commodities
Following
Seed
Treatment:
Lab
Project
Number:
AA970775.
Unpublished
study
prepared
by
American
Agricultural
Services,
Inc.
58
p.
56
GS
00010:
San
Antonio,
J.
P.
"Demonstration
of
Lindane
and
a
Lindane
Metabolite
in
Plants
by
Paper
Chromatography."
Ag.
and
Food
Chem.,
7,
322
(1959).
GS
00012:
Herbst
M.
and
G.
Leber.
"Investigations
on
Lindane
either
in
Progress
or
Planned."
Presented
at
the
EPA
in
Washington,
12/
18/
75.
GS
00013:
Itokawa,
H.,
et
al.
"Beitrage
zur
Okologischen
Chemie
XXII,
Metabolismus
und
Ruckverhalten
von
Lindan
14C
in
honeren
Pflanzen,
Tetrahedron,
26,
763
773,
1970.
GS
00014:
Lindane
Position
Document
2/
3,
1980.
GS
00015:
Lindane
Position
Document
4,
1984.
GS
00016:
R.
W.
Chadwick,
et
al.
"Enhanced
Pesticide
Metabolism,
a
Previously
Unreported
Effect
of
Dietary
Fibre
in
Mammals."
Fd.
Cosmet.
Toxicol.,
16,
217
225
(1978).
GS
00017:
Ivey,
M.
C.,
et
al.
"Lindane
Residue
in
Chickens
and
Eggs
Following
Poultry
House
Spray,"
J.
of
Ecom.
Entomol.,
54(
3):
487
488
(1961).
GS
00018:
BHC
Lindane
Report,
Special
Pesticide
Review
group.
GS
00019
(Section
18
Exemption
for
the
use
of
lindane
on
sugarcane
in
Puerto
Rico,
4/
14/
80).
GS
00021:
PP
#058,
Acc.
No.
113144.
GS
00022:
No
citation
available
GS
00023:
Oehler,
D.
D.,
et
al.
"Residues
in
Milk
Following
Treatment
of
Cows
with
Lindane
or
Ronnel
to
Control
Screw
worms,"
J.
Econ.
Entomol.,
63,
1467
(1970).
| epa | 2024-06-07T20:31:43.063620 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0202-0005/content.txt"
} |
EPA-HQ-OPP-2002-0202-0006 | Supporting & Related Material | "2002-08-14T04:00:00" | null | 1
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
Date:
April
30,
2002
MEMORANDUM
SUBJECT:
REVISED
OCCUPATIONAL
AND
RESIDENTIAL
EXPOSURE
ASSESSMENT
AND
RECOMMENDATIONS
FOR
THE
RE
REGISTRATION
ELIGIBILITY
DECISION
DOCUMENT
FOR
LINDANE
FROM
David
Jaquith
Reregistration
Action
Branch
4
Health
Effect
Division
(7509C)
TO:
Becky
Daiss
Reregistration
Branch
4
Health
Effect
Division
(7509C)
THRU
Susan
Hummel,
Senior
Scientist
Reregistration
Branch
4
Health
Effects
Division
(7509C)
Please
find
attached
the
occupational
and
residential
exposure
assessment
for
lindane
DP
BARCODE
D282648
Pesticide
Chemical
Codes:
009001
EPA
Reg
Nos:
EPA
MRID
Nos.:
452000
02,
444058
02,
422519
01
PHED:
No
2
CONTENTS
EXECUTIVE
SUMMARY......................................................
3
1.0
BACKGROUND
........................................................
4
1.1
Summary
of
Toxicity
Concerns
Relating
to
Occupational
Exposures
.........
5
1.
2
Summary
of
Use
Pattern
and
Formulations..............................
7
1.3
Method
and
Types
of
Equipment
Used
for
Mixing/
Loading/
Applying
........
8
1.
4
Incident
Reports...................................................
8
2.0
OCCUPATIONAL
EXPOSURES
...........................................
8
2.1
Handler
Exposures
&
Assumptions
....................................
8
2.1.1
Submitted
Studies
...........................................
8
2.1.2
Summary
of
Occupational
Handler
Exposures
.....................
9
2.1.3
Summary
of
Uncertainties
.....................................
9
2.1.4
Calculations
of
Exposure
.....................................
11
2.2
Risk
From
Handler
Exposures
.......................................
12
2.2.1
Risk
From
Handler
Exposures
................................
12
2.2.2
Summary
of
MOEs
.........................................
13
2.2.3
Cancer
Risks
..............................................
13
2.2.3
Insufficient
Data
...........................................
13
REFERENCES
..................................................
16
Appendix
A
...........................................................
17
Appendix
B
...........................................................
22
Appendix
C
...........................................................
29
3
Executive
Summary
This
document
presents
the
occupational
exposure
assessment
for
use
of
lindane.
Lindane
is
the
gamma
isomer
of
1,2,3,4,5,6
hexachlorocyclohexane,
an
insecticide
previously
used
in
many
situations
but
now
restricted
to
seed
treatment
only.
There
are
no
current
registered
uses
for
recreational,
residential
or
other
public
(non
occupational)
settings.
All
uses
other
than
seed
treatment
have
been
cancelled.
Lice
and
scabies
treatment
is
considered
in
the
risk
assessment
document.
Acute
Toxicity
Categories
Acute
toxicity
categories
for
technical
grade
lindane
are
in
Toxicity
Category
II
for
oral,
Toxicity
Category
II
for
dermal,
and
Toxicity
Category
II
for
inhalation.
It
is
in
Toxicity
Category
III
for
primary
eye
irritation.
The
endpoints
used
in
this
document
to
assess
lindane
hazards
include
short
term
and
intermediate
term
dermal
and
inhalation
endpoints.
The
exposure
duration
for
short
term
assessments
is
1
to30
days
or
up
to
1
month.
Intermediate
term
duration
is
greater
than
1
month
to
six
months.
Although
there
is
little
information
to
determine
what
percentage
of
workers
apply
for
more
than
one
month,
it
is
reasonable
to
believe
that
typical
uses
of
lindane
by
commercial
seed
treatment
facilities
may
encompass
an
intermediate
term
duration.
On
farm
treatments
are
more
likely
to
be
of
short
term
duration.
An
oral
developmental
neurotoxicity
study
(MRID
45073501)
in
rats
was
selected
for
both
dermal
assessments.
A
90
day
inhalation
toxicity
study
(MRID
00255003)
was
selected
for
inhalation
assessment
for
all
time
periods.
In
the
developmental
neurotoxicity
study
the
maternal
toxicity
NOAEL
is
50
ppm
(5.6
mg/
kg/
day)
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
The
offspring
toxicity
NOAEL
was
10
ppm
(1.2
mg/
kg/
day).
In
the
subchronic
inhalation
toxicity
study
(Accession
No.
255003)
Tte
systemic
toxicity
NOAELs
for
short
term
exposure
was
0.5
mg/
m
3
(0.13
mg/
kg/
day),
based
on
lesions
in
the
kidney
and
increased
kidney
weights.(
1).
Exposure
data
on
lindane
are
available
but
limited.
An
exposure
study
addressing
on
farm
seed
treatment
has
been
conducted
(MRID
444058
02).
A
detailed
description
along
with
the
exposure
calculations
are
presented
in
Appendix
A.
Another
study
addressing
commercial
seed
treatment
with
another
chemical
has
been
reviewed
by
the
Agency.
The
an
excerpt
of
the
review
of
that
study
(MRID
452000
02),
along
with
the
calculations
for
lindane
exposure
are
presented
in
Appendix
B.
The
results
of
the
handler
assessments
indicate
that
the
on
farm
seed
treatment
provide
dermal
MOEs
less
than
100
with
the
attire
worn
during
the
study
(long
pants,
long
sleeved
shirts,
gloves).
The
assessments,
both
dermal
and
inhalation,
yielded
MOEs
of
less
than
100
for
4
mixing/
loading/
application
and
bagging/
sewing/
stacking
during
commercial
seed
treatment
of
canola.
All
other
exposure
scenarios
provide
MOEs
greater
than
or
equal
to
100
when
wearing
the
clothing
used
in
the
study
(coveralls
over
single
layer
of
clothing,
gloves
for
commercial
other
seed
treatment
workers)
or
at
baseline
attire
(single
layer
of
clothing,
gloves
for
mixer/
loaders)
for
loading
seed
for
planting
or
for
planting
treated
seed.
Due
to
the
method
of
seed
treatment,
HED
has
determined
that
soil
incorporated,
postapplication
agricultural
exposure
is
considered
to
be
negligible
as
long
as
the
soil
is
not
directly
contacted.
The
exception
is
farmers
handling
treated
seed.
An
estimate
of
the
inherent
risk
from
handling
treated
seed
was
conducted
using
relatively
conservative
assumptions.
There
are
no
study
data
available
on
exposure
to
lindane
from
handling
treated
seed
and
therefore
the
exposure
was
estimated
using
surrogate
data.
An
excerpt
of
that
review
of
that
study
(MRID
422519
01)
and
exposure
calculations
are
presented
in
Appendix
C.
1.0
BACKGROUND
Purpose
This
document
is
for
use
in
development
of
the
Reregistration
Eligibility
Decision
Document
(RED)
for
the
insecticide
lindane
and
presents
a
review
of
the
potential
human
health
effects
of
occupational
exposure
to
lindane.
Criteria
for
Conducting
Exposure
Assessments
An
occupational
and/
or
residential
exposure
assessment
is
required
for
an
active
ingredient
if
(1)
certain
toxicological
criteria
are
triggered
and
(2)
there
is
potential
exposure
to
handlers
(mixers,
loaders,
applicators,
etc.)
during
use
or
to
persons
entering
treated
sites
after
application
is
complete.
For
lindane,
both
of
these
criteria
are
met.
5
1.1
Summary
of
Toxicity
Concerns
Relating
To
Occupational
Exposures
Acute
Toxicology
Categories
Table
1
presents
the
acute
toxicity
categories
as
outlined
in
the
Report
of
the
Hazard
Identification
Assessment
Review
Committee
(1).
Table
1:
Acute
Toxicity
Categories
for
Lindane
(Technical)
STUDY
TYPE
MRID
CATEGORY
RESULT
81
1
Acute
oral
00049330
II
LD50
88
mg/
kg
males
91
mg/
kg
females
81
2
Acute
dermal
00109141
II
LD50
1000
mg/
kg
males
900
mg/
kg
females
81
3
Acute
inhalation
Acc.
263946
III
LC50
1.56
mg/
L
both
sexes
81
4
Eye
irritation
Acc.
263946
III
PIS
=
0.6
no
corneal
involvement
irritation
cleared
after
24
hours
81
5
Dermal
irritation
Acc.
263946
IV
PIS
=
0
not
an
irritant
81
6
Dermal
sensitization
Acc.
263946
NA
not
a
sensitizer
Other
Endpoints
of
Concern
The
Report
of
the
Hazard
Identification
Assessment
Review
Committee
(HIARC)
for
lindane,
(1)
indicates
that
there
are
toxicological
endpoints
of
concern
for
lindane.
The
endpoints
used
in
assessing
the
risks
for
lindane
are
presented
in
Table
2.
6
Table
2.
Doses
and
Toxicological
Endpoints
Selected
for
Risk
Assessment
of
Lindane
EXPOSURE
SCENARIO
DOSE
(mg/
kg/
day)
ENDPOINT
STUDY
TYPE/
MRID
Acute
Dietary
general
population
NOAEL=
6
mg/
kg
UF
=
100
LOAEL
is
20
mg/
kg
based
on
increased
grip
strength,
increased
motor
activity
Acute
Neurotoxicity
in
Rats/
44769201
Acute
RfD
=
0.06
mg/
kg/
day
aPAD
=
0.02
mg/
kg/
day
Chronic
Dietary
NOAEL=
0.47
mg/
kg/
day
UF
=
300
LOAEL
is
100
ppm
(4.81
mg/
kg/
day)
periacinar
hepatocyte
hypertrophy,
increased
liver/
spleen
weight,
decreased
platelets
Chronic
Feeding
and
Carcinogenicity
in
Rats
41094101,
41853701
42891201
Chronic
RfD
=
0.0047
mg/
kg/
day
cPAD
=
0.0016
mg/
kg/
day
Short
Term
1
(Dermal)
NOAEL=
1.2
mg/
kg/
day
LOAEL
is
50
ppm
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
Developmental
Neurotoxicity
Study
in
Rats
(oral)
45073501
Intermediate
Term
1
(Dermal)
NOAEL=
1.2
mg/
kg/
day
LOAEL
is
50
ppm
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
Developmental
Neurotoxicity
Study
in
Rats
(oral)
45073501
Long
Term
1
(Dermal)
NOAEL=
0.47
mg/
kg/
day
LOAEL
is
100
ppm
(4.81
mg/
kg/
day)
periacinar
hepatocyte
hypertrophy,
increased
liver/
spleen
weight,
decreased
platelets
Chronic
Feeding
and
Carcinogenicity
in
Rats
41094101,
41853701
42891201
Dermal
Absorption
Factor
=
10%
Short
Term
1
(Inhalation)
0.13
mg/
kg/
day
(0.5
mg/
m
3
)
based
on
clinical
signs
(diarrhea,
piloerection)
seen
at
day
14
and
continuing
for
20
days
90
Day
Inhalation
Toxicity
/
00255003
Intermediate
Term
1
(Inhalation)
0.13
mg/
kg/
day
(0.5
mg/
m
3
)
LOAEL
is
5.0
mg/
m
3
based
on
increased
kidney
weights
of
female
rats
and
bone
marrow
effects.
90
Day
Inhalation
Toxicity
/
00255003
Long
Term
2
(Inhalation)
N/
A
N/
A
N/
A
1
Since
an
oral
NOAEL
was
selected,
the
dermal
absorption
factor
(10%)
should
be
used
in
route
to
route
extrapolation.
2
Exposure
thru
this
route
for
this
duration
is
not
expected
7
1.2
Summary
of
Use
Patterns
and
Formulations
The
only
use
remaining
for
lindane
is
for
seed
treatment.
The
use
closure
memorandum
(4)
allows
the
seed
treatment
of
the
following
crops:
barley,
broccoli,
Brussels
sprouts,
cabbage,
cauliflower,
corn,
lettuce,
oats,
radishes,
rye,
sorghum,
spinach,
and
wheat.
The
crops
and
application
rates
are
presented
in
Table
3.
Wheat
and
canola
were
used
as
a
representative
crops
for
all
other
seeds
treated
with
lindane
because
of
the
relatively
large
farm
size,
application
rate,
and
nature
of
the
product
treated.
Table
3.
Summary
of
Application
Rates
for
Seed
Treatment
Using
Lindane
on
Various
Crops.
Commodity
Formulation/
Reg.
No.
Use
Rate
barley
0.0375
lb
ai/
100
pound
seed
corn
dust
(19713
262)
EC
(71096
2)
0.125
lb
ai/
bushel
seed
0.125
lb
ai/
100
pound
seed
oats
7501
38,
10107
121
0.03125
lb
ai/
100
pound
seed
rye
19713
401
554
144
19713
387
0.032813
lb
ai/
100
pound
seed
sorghum
42056
15
0.0628
lb
ai/
100
pound
seed
spinach
dust
(7501
38,
34704
653,
34704
658,
19713
262,
34704
658,
42056
14,
10107
121,
66330
19)
0.0625
lb
ai/
100
pound
seed
wheat
dust,
2935
492
0.042578
lb
ai/
100
pound
seed
canola
Not
currently
registered
1.5
lb
ai/
100
pounds
seed
(a
rate
of
0.75
lb/
100
lbs
seed
has
been
proposed)
1.3
Method
and
Type
of
Equipment
Used
for
Mixing/
Loading/
Applying
The
flowable
concentrate,
and
emulsifiable
concentrate
formulations
for
commercial
application
all
require
mixing
with
water
to
the
label
specified
dilution.
This
is
usually
performed
by
scooping
or
pouring
the
formulation
into
a
mixing
tank,
often
of
100
gallons
or
more
in
capacity,
with
mechanical
agitation
to
keep
the
resulting
emulsion
homogenized
and
prevent
variations
in
application
strength.
Smaller
amounts
may
be
handled
using
a
tiller
planter
(or
seed
drill)
mounted
system.
Large
commercial
operations,
may
have
mechanical,
automated,
8
metered
pumps
which
require
only
connecting
the
formulation
to
the
pump.
Again,
small
seed
treatment
operations,
such
as
seed
box
(or
"hopper
box")
mixing,
may
be
done
by
pouring
small
amounts
in
to
a
mixing
device
before
planting
the
seeds
in
to
the
soil.
Dry
formulations
may
also
be
used,
particularly
for
on
farm
treatment.
Timing
and
Frequency
of
Application
Generally,
seed
will
be
treated
on
an
as
needed
basis.
However,
it
is
industry
practice
only
to
treat
enough
seeds
as
are
needed
to
be
used
that
season.
1.4
Incident
Data
No
information
regarding
seed
treatment
incidents
is
available
at
this
time.
2.0
OCCUPATIONAL
EXPOSURES
2.1
Handler
Exposures
&
Assumptions
HED
has
determined
that
there
are
potential
exposures
to
mixers,
loaders,
applicators,
or
other
handlers
during
usual
use
patterns
associated
with
lindane.
Based
on
the
use
patterns
and
potential
exposures
described
above,
5
major
exposure
scenarios
were
identified
to
represent
the
extent
of
lindane
uses:
(1)
mixing/
loading/
application
of
formulations
for
on
farm
seed
treatment,
(2)
mixing/
loading
and
applying
liquid
with
commercial
seed
treatment
equipment,
(3)
bagging
and
otherwise
handling
treated
seeds,
(5)
forklift
operation,
(6)
cleaning
seed
treatment
equipment,
(7)
mixing/
loading/
planting
of
treated
seed
for
planting.
2.1.1
Submitted
Studies
Mixer/
loader/
applicator
exposure
data
for
lindane
were
required
since
one
or
more
toxicological
criteria
had
been
triggered.
Requirements
for
applicator
exposure
studies
are
addressed
by
Series
875
Group
A
(formerly
Subdivision
U
of
the
Pesticide
Assessment
Guidelines).
Three
exposure
studies,
one
addressing
on
farm
treatment
have
been
provided
(Appendix
A),
another
addressing
commercial
seed
treatment
(Appendix
B),
a
third
addressing
planting
of
treated
seed
(Appendix
C)
2.1.2
Summary
of
Occupational
Handler
Exposures
Table
5
presents
the
exposure
scenarios,
application
rates,
and
amount
potentially
handled
that
have
been
used
for
the
exposure
calculations.
These
are
restricted
to
canola
and
wheat
for
commercial
seed
treatment
and
wheat
for
on
farm
treatments
as
representative
of
typical
applications.
Exposures
for
handling
treated
seed
before
planting
and
planting
treated
seed
use
parameters
for
wheat
and
canola
as
representative
crops.
Therefore,
the
rates/
seed
types
presented
in
Table
5
are
not
all
conclusive
and
no
attempt
has
been
made
to
assess
a
range
of
application
rates
to
ensure
that
all
use
rates
and
exposure
scenarios
are
represented.
9
2.1.3
Summary
of
Uncertainties
The
assumptions
and
uncertainties
are
identified
below
to
be
used
in
risk
management
decisions:
C
Application
Rates:
Based
on
wheat
for
on
farm
treatment
and
canola
for
commercial
seed
treatment.
Other
types
of
seed
may
have
slightly
different
rates
but
these
differences
are
unlikely
to
appreciably
alter
the
exposure/
risk
assessment.
C
Amount
Handled:
For
commercial
seed
treatment
the
amounts
handled
are
assumed
to
be
equal
to
the
amounts
handled
at
the
facilities
used
in
the
study
described
in
the
Appendices.
On
farm
treatment
exposures
were
estimated
assuming
that
enough
wheat
seed
could
be
treated
and
planted
for
100
acres
per
day
at
a
rate
of
120
pounds
of
seed
per
acre.
C
Unit
Exposures:
The
unit
exposure
values
for
commercial
seed
treatment
and
planting
of
treated
seed
were
derived
from
surrogate
studies.
The
median
exposure
value
was
used
for
commercial
seed
treatment
(Appendix
B)
and
the
arithmetic
mean
was
used
for
the
loading/
planting
task
(Appendix
C).
10
Table
4:
Exposure
Variables
for
Uses
of
Lindane
Exposure
Scenario
(Scenario
#)
Are
Chemical
Specific
Monitoring
Data
Available
Are
PHED
Data
Available?
Application
Rates
(lb
ai/
amt
of
seed)
Daily
lb
Seed
Treated/
Handled
Lb
ai
Handled/
day
Applicator/
Handler
Exposure
(1)
mixing/
loading/
planting
of
dry
formulations
for
on
farm
treatment
Yes
MRID
#44440585
02
No
0.023
lb
ai/
bushel
(60
lbs
seed)
for
wheat
12000
lbs
seed,
see
Appendix
A)
4.7
a
(2)
mixing/
loading
and
applying
liquid
with
a
commercial
seedtreatment
equipment
No
MRID
#45200002
No
Wheat:
0.043lb
ai/
100
lb
seed
treated
176000
76
Canola
(low
end):
0.75
lb
ai/
100
lb
seed
treated
176000
1320
Canola
(high
end):
1.5
lb
ai/
100
lb
seed
treated
176000
2640
(3)
handler
for
commercial
seedtreatment
equipment
(i.
e.
bagging,
sewing,
stacking)
with
chemical
resistant
coveralls
over
long
sleeve
shirt
long
pants,
chemical
resistant
gloves
No
MRID
#45200002
No
Wheat:
0.043lb
ai/
100
lb
seed
treated
176000
76
Canola
(low
end):
0.75
lb
ai/
100
lb
seed
treated
176000
1320
Canola
(high
end):
1.5
lb
ai/
100
lb
seed
treated
176000
2640
(4)
handler
for
commercial
seedtreatment
equipment
(i.
e.
bagging,
sewing,
stacking)
with
cotton/
polyester
coveralls
over
long
sleeve
shirt
long
pants,
chemical
resistant
gloves
No
MRID
#45200002
No
Wheat:
0.043lb
ai/
100
lb
seed
treated
176000
76
Canola
(low
end):
0.75
lb
ai/
100
lb
seed
treated
176000
1320
Canola
(high
end):
1.5
lb
ai/
100
lb
seed
treated
176000
2640
(5)
Forklift
operator
chemical
resistant
coveralls
over
long
sleeve
shirt
long
pants,
chemical
resistant
gloves
No
MRID
#45200002
No
Wheat:
0.043lb
ai/
100
lb
seed
treated
176000
76
Canola
(low
end):
0.75
lb
ai/
100
lb
seed
treated
176000
1320
Canola
(high
end):
1.5
lb
ai/
100
lb
seed
treated
176000
2640
(6)
Worker
Cleaning
seed
treatment
equipment
chemical
resistant
coveralls
over
long
sleeve
shirt
long
pants,
chemical
resistant
gloves
No
MRID
#45200002
No
Wheat:
0.043lb
ai/
100
lb
seed
treated
NA
NA
Canola
(low
end):
0.75
lb
ai/
100
lb
seed
treated
NA
NA
Table
4:
Exposure
Variables
for
Uses
of
Lindane
Exposure
Scenario
(Scenario
#)
Are
Chemical
Specific
Monitoring
Data
Available
Are
PHED
Data
Available?
Application
Rates
(lb
ai/
amt
of
seed)
Daily
lb
Seed
Treated/
Handled
Lb
ai
Handled/
day
11
Canola
(high
end):
1.5
lb
ai/
100
lb
seed
treated
NA
NA
(7)
Planting
treated
seed
Enclosed
cab
No
MRID
#42251901
No
Wheat:
0.043lb
ai/
100
lb
seed
treated
3000
12.9
Canola
(low
end):
0.75
lb
ai/
100
lb
seed
treated
1000
7.5
Canola
(high
end):
1.5
lb
ai/
100
lb
seed
treated
1000
15
a
Data
are
available
from
on
farm
treatment
study
(Appendix
A)
c
Daily
amount
treated
based
on
HEDs
estimates
of
acreage
that
would
be
reasonably
expected
to
be
planted
in
a
day
for
commercially
treated
seed.
The
acres
per
day
assumed
120
lbs.
of
wheat
per
acre,
planting
an
average
of
250
acres
per
day
(2).
2.2
Risk
From
Handler
Exposures
EPA
calculated
the
potential
risk
to
persons
from
handler
exposures
and
planting
of
treated
seed
using
the
daily
dermal
exposure
scenarios
identified
in
the
exposure
section.
Potential
dermal
and
inhalation
daily
exposures
for
occupational
handlers
were
calculated
using
the
following
formulas
(10
percent
dermal
absorption
was
assumed):
The
inhalation
and
dermal
daily
doses
were
calculated
using
the
following
formulas:
12
2.2.1
Risk
From
Handler
Exposures
Margins
of
Exposure
(MOEs)
were
calculated
for
handlers
for
short
term
(one
to
seven
days)
and
intermediate
term
(one
week
to
several
months)
durations
for
both
dermal
and
inhalation
exposures.
The
MOEs
were
calculated
using
the
following
formulas:
13
2.2.2
Summary
of
MOEs
The
daily
exposures,
resulting
short
and
intermediate
term
MOEs
are
presented
in
Table
7.
The
exposure
scenario
descriptions
are
presented
in
Table
8.
The
results
of
the
short
term
dermal
exposure
duration
indicate
that
the
MOEs
range
from
5.2
for
on
farm
seed
treatment
to
34000
for
the
planting
of
treated
seed
.
A
total
of
9
dermal
and
inhalation
MOEs
were
calculated
for
the
various
scenarios.
Based
on
the
level
of
protection
used
in
the
studies,
all
of
the
MOEs
for
the
application
portion
of
seed
treatment
were
less
than
100.
All
other
dermal
MOEs
were
above
100.
Inhalation
MOEs
for
workers
other
than
applicators
for
commercial
treatment
and
seed
handlers
at
large
facilities
are
greater
than
100.
2.2.3
Cancer
Risks
The
OPP/
Cancer
Assessment
Review
Committee
(CARC)
has
completed
the
review
of
newly
submitted
carcinogenicity
study
in
CD
1
mice
along
with
other
data.
In
accordance
with
the
EPA
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(July,
1999),
the
CARC
has
classified
lindane
into
the
category
"Suggestive
evidence
of
carcinogenicity,
but
not
sufficient
to
assess
human
carcinogenic
potential"
based
on
an
increased
incidence
of
benign
lung
tumors
in
female
mice
only.
The
Committee,
therefore,
recommended
that
the
quantification
of
human
cancer
risk
is
not
required.
2.2.4
Insufficient
Data
Other
studies
are
undergoing
review
by
HED
personnel
at
this
time
and
may
alter
our
estimate
of
exposure.
14
Table
5
Daily
Exposures
and
MOEs
for
Commercial
Seed
Treatment
Plant
Worker
Exposure
Exposure
Scenario
(Scenario
#)
Application
Rates
(
lb
ai/
100
lbs
seed
or
Lb/
A)
Amount
Handled
per
Day
(lbs
a.
i.)
Unit
Exposure
(mg/
lb
ai)
a
Daily
Exposure
(mg/
kg/
day)
Short
Term
MOEs
&
Intermediate
Term
MOES
Dermal
Inhalation
Dermal
b
Inhalation
s
Dermal
c
Inhalation
e
Mixing/
loading
/planting
dry
formulation
for
on
farm
seed
treatment
(1)
0.043
4.7
9.4
0.
0016
0.074
0.00011
16
1200
Treater
Closed
Transfer
chemical
resistant
coveralls
over
long
sleeved
shirt,
long
pants,
chemical
resistant
gloves
(2)
1.5
(canola
high
end)
76
0.00083
0.00012
0.036
0.0053
329
25
0.75
(canola
low
end)
1320
0.00083
0.00012
0.018
0.0026
657
49
0.043
(wheat)
2640
0.00083
0.00012
0.0010
0.00015
11462
859
Bagger/
Sewer
/Stacker
chemical
resistant
coveralls
over
long
sleeved
shirt,
longpants,
chemical
resistant
gloves
(3)
1.5
(canola
high
end)
76
0.00026
0.00006
0.011
0.0026
1049
49
0.75
(canola
low
end)
1320
0.00026
0.00006
0.0057
0.0013
2098
98
0.043
(wheat)
2640
0.00026
0.00006
0.00033
0.000076
36591
1718
Bagger/
Sewer
/Stacker
cotten/
polyester
coveralls
over
long
sleeved
shirt,
longpants,
chemical
resistant
gloves
(4)
1.5
(canola
high
end)
76
0.0003
0.00006
0.013
0.00264
909
49
0.75
(canola
low
end)
1320
0.0003
0.00006
0.0066
0.0013
1818
98
0.043
(wheat)
2640
0.0003
0.00006
0.00038
0.000076
31712
1718
Forklift
Operator
chemical
resistant
coveralls
over
long
sleeved
shirt,
longpants,
chemical
resistant
gloves
(5)
1.5
(canola
high
end)
76
0.00008
7.7E
06
0.
0035
0.00034
34091
384
0.75
(canola
low
end)
1320
0.00008
7.7E
06
0.
0018
0.00017
6818
767
0.043
(wheat)
2640
0.00008
7.7E
06
0.
00010
9.7E
06
118922
13385
Cleaner
chemical
resistant
coveralls
over
long
sleeved
shirt,
longpants,
chemical
resistant
gloves
(6)
1.5
(canola
high
end)
76
0.00669
0.00119
0.00011
1.98E
05
107623
6555
0.75
(canola
low
end)
1320
0.00669
0.00119
0.00011
1.98E
05
107623
6555
0.043
(wheat)
2640
0.00669
0.00119
0.00011
1.98E
05
107623.3
6555
a
Median
unit
dermal
and
arithmetic
mean
inhaltion
unit
exposures
b
Dermal
Exposure
(mg/
kg/
day)
=
unit
exposure
(mg/
lb
ai)
x
amount
handled
per
day
(lbs
a.
i.)
/
bw
(60
kg).
c
Dermal
MOE
=
Dermal
NOAEL
(1.
2
mg/
kg)
/
[daily
exposure
(mg/
kg/
day)
x
dermal
absorption
factor
(10%)].
d
Inhalation
Exposure
(mg/
kg/
day)
=
inhalation
unit
exposure
(mg/
lb
ai)
x
amount
handled
per
day
(lbs
a.
i.)
/
body
weight
(70
kg).
e
Inhalation
MOE
=
NOAEL
(0.
13
mg/
kg/
day)
/
daily
exposure
(mg/
kg/
day).
15
Table
6.
Exposure
Scenario
Descriptions
for
the
Use
of
Lindane.
Exposure
Scenario
(Scenario
#)
Data
Source
Standard
Assumptions
a
Comments
b
Mixing/
loading
/planting
dry
formulation
for
on
farm
seed
treatment
(1)
Rhone
Poulenc
Data
MRID
#
444058
02
Assumes
enough
seed
treated
and
planted
for
100
Acres
per
day
All
data
were
for
gloved
hands;
(see
study,
Appendix
A.
)
Mixing/
loading/
application
of
liquid
formulation
for
commercial
seed
treatment
(2)
Uniroyal
Data
MRID
#
447305
01
176000
lbs
of
seed
per
day
See
study
review;
based
on
geometric
mean
of
data
and
amounts
of
seed
from
study
data
Seed
Handler
for
commercial
seed
treatment
(3,
4,5,6)
Uniroyal
Data
MRID
#
447305
01
176000
lbs
of
seed
per
day
See
study
review;
based
on
geometric
mean
of
data
and
amounts
of
seed
from
study
data
Loading
and
planting
treated
seed
for
planting
(7)
MRID
422519
01
Assumes
250
acres
are
planted
per
day
at
120
lbs
of
seed
per
acre
for
wheat;
4
lbs
per
acre
for
canola,
commercially
treated
seed
Appendix
C
a
All
Standard
Assumptions
are
based
on
an
8
hour
work
day
as
estimated
by
HED.
16
REFERENCES
1)
Lindane
Report
of
the
Hazard
Identification
Assessment
Review
Committee,
July
27,
2000.
2)
Memorandum
from
S.
Tadayon
(CEB1)
to
A.
Khasawinah
(RRB4)
titled
"Occupational
and
Residential
Exposure
Assessment
and
Recommendations
for
the
Registration
Eligibility
Decision
Document
for
Imazalil",
dated
April
15,
2,000.
3)
EPA
(1998)
Surrogate
Exposure
Guide,
Estimates
of
Worker
Exposure
from
the
Pesticide
Handler
Exposure
Database
Version
1.1
4)
Memorandum
from
M.
Howard
(SRRD)
to
Lindane
RED
Team
Members
titled
"Final
Lindane
Use
Closure
Memo"
dated
May
17,
2000
(EMAIL).
cc:
Lindane
file
(009001)
Correspondence
file
R.
Kent
(RRB4/
7509C)
D.
Jaquith
(RRB4/
7509C)
17
APPENDIX
A.
MANUAL
SEED
TREATMENT
(at
farm):
CITATION:
Fenske,
R.
A.,
A.
M.
Blacker,
S.
J.
Hamburger,
and
G.
S.
Simon
(1990)
Worker
Exposure
and
Protective
Clothing
Performance
During
Manual
Seed
Treatment
with
Lindane.
Arch.
Environ.
Contam.
Toxicol.
19,
190
196.
Fenske,
R.
A.
Reregistration
of
Lindane
Technical
Case
No.
0315,
Chemical
No.
9001.
Worker
Exposure
to
Lindane
During
Manual
Seed
Treatment.
MRID
No.
444058
02
Dermal
and
respiratory
exposures
of
4
male
workers
with
prior
experience
were
monitored
during
the
manual
treatment
of
winter
wheat
at
a
commercial
wheat
farm
in
South
Dakota.
The
operations
are
considered
to
be
representative
of
manual
seed
treatments
in
the
midwest.
A
dust
formulation
containing
18.75
percent
lindane,
packaged
in
10
lb
bags
was
applied
at
the
label
rate
of
2
ounces
per
bushel
of
seed.
A
total
of
720
bushels
of
seed
were
treated.
The
treatment
procedure
involved
the
addition
of
grain
to
a
4
compartment,
12
bushel
grain
drill.
The
label
instructions
indicate
the
user
is
to
fill
the
drill
box
half
full
of
seed
and
add
half
of
the
formulation.
The
seed
and
formulation
are
then
mixed
with
a
stick.
The
rest
of
the
grain
is
then
added
and
the
procedure
repeated.
After
thorough
mixing
the
seed
was
removed
by
a
vacuum.
Workers
monitored
in
this
study
did
not
participate
in
the
vacuuming
procedure.
Each
mixing
consisted
of
the
application
of
24
oz
(680
g)
of
the
formulation
to
12
bushels
of
grain.
A
plastic
scoop,
cut
from
a
plastic
bottle
and
determined
to
hold
12
oz
of
formulation,
was
used
to
remove
the
powder
from
the
bag.
The
scoop
was
used
to
spread
the
formulation
evenly
over
the
seed.
Each
replicate
consisted
of
five
mixings
conducted
by
each
of
the
four
workers,
the
mixing
activity
lasting
4
6
minutes.
The
mixing
periods
averaged
24
minutes
and
were
separated
by
10
20
minute
breaks.
This
was
considered
to
be
equal
to
one
"work
period".
During
this
time
a
worker
handled
120
oz
of
formulation
or
1.4
lb
of
active
ingredient.
Each
volunteer
performed
the
tasks
three
times
(total
of
60
mixings),
yielding
a
total
of
12
work
periods.
During
treatments
the
workers
wore
the
label
required
long
sleeve
shirt,
long
pants,
Nitrile
gloves,
a
baseball
cap,
and
a
pesticide
respirator.
All
clothing
was
new
and/
or
prewashed
to
avoid
confounding
analytical
problems.
The
workers
did
not
remove
their
gloves
during
the
procedure
but
did
during
breaks.
Dermal
exposures
were
monitored
using
gauze
dosimeters
encased
in
an
envelope
with
a
5.6
cm
diameter
circle
exposed
to
the
environment
(25
cm²
total
area).
Dosimeters
were
either
attached
to
the
clothing
or
taped
to
the
skin
on
the
chest,
back,
shoulders,
forearms,
upper
legs,
or
lower
legs.
Two
sets
of
dosimeters
were
used,
one
outside
the
clothing
and
the
other
inside
the
work
garments.
Care
was
taken
to
avoid
overlap
of
the
dosimeters,
which
could
confound
the
results
of
the
inner
monitors.
Surface
areas
were
assumed
to
be
those
outlined
in
the
Agency's
Guidance
(OPPTS
875
Group
A
test
guidelines,
formerly
Subdivision
U).
Dermal
exposure
of
the
hands
was
monitored
by
hand
wash
with
250
mL
of
10
percent
isopropanol
in
distilled
water.
A
plastic
bag
was
wrapped
around
the
wrist
and
the
bag
shaken
for
about
30
seconds.
This
procedure
was
repeated
3
times,
resulting
in
a
pooled
volume
of
750
mL
for
each
hand.
Hand
rinses
were
conducted
for
each
hand
immediately
prior
to
the
exposure
period
and
again
18
immediately
after.
Approximately
75
mL
was
transferred
to
a
glass
jar
for
storage.
Respiratory
exposure
was
monitored
using
calibrated
battery
powered
pumps
attached
to
the
belt
with
a
37
mm
fiberglass
filter
attached
to
the
collar
in
the
breathing
zone.
The
flow
rate
was
approximately
2
liters
per
minute.
Dermal
dosimeters
and
air
filter
cassettes
were
removed
immediately
after
the
exposure
period.
Gauze
pads
were
removed
from
their
holders
with
solvent
rinsed
tweezers
and
placed
in
individual
4
ounce
glass
jars.
Filter
were
sealed
and
replaced
in
their
original
packing
containers.
All
samples
were
maintained
at
4°
C
during
shipment
and
storage.
Samples
arrived
at
the
analytical
laboratory
within
6
days
of
collection
and
analyzed
within
the
next
2
months.
Fifty
mL
of
hexane/
acetone
(1/
1,
v/
v)
was
added
to
the
dermal
dosimeters
jars
and
the
jars
shaken
for
1
hour.
A
100
:
L
aliquot
of
the
extract
was
added
to
a
10
mL
volumetric
flask
and
2
:
L
of
internal
standard/
surrogate
chemical
(aldrin
and
heptachlor,
respectively).
The
resulting
solution
was
brought
to
volume
with
hexane
The
results
of
exposure
monitoring
are
presented
in
Table
A1.
19
Table
A1.
Exposures
of
Workers
Applying
Lindane
as
a
Seed
Treatment
at
a
Rate
of
1.4
lb
ai)
Pounds
of
Active
Ingredient
per
60
Bushels
of
Grain
(3600
lbs
of
seed,
total.
Values
used
for
exposure
estimation
are
in
boldface.
Body
Region
Monitor
Location
Exposure
(mg)
Exposure
(mg/
lb
ai)
Mean
Median
Range
Mean
Median
Chest
Outer
3.21
2.43
0.92
7.84
2.3
1.7
Back
Outer
2.48
2.48
0.85
4.58
1.8
1.8
Forearms
Outer
17.75
15.25
5.57
51.79
13.0
11.0
Upper
arms
Outer
4.43
3.88
0.99
10.10
3.2
2.7
Upper
legs
Outer
33.96
20.46
2.90
132.55
24.0
15
Lower
legs
Outer
1.34
9.64
0.43
5.95
0.96
6.9
Chest
Inner
0.45
0.44
0.07
0.71
0.32
0.31
Back
Inner
0.71
0.52
0.11
2.59
0.51
0.37
Forearms
Inner
5.43
3.46
1.31
16.70
3.9
2.5
Upper
arms
Inner
1.12
0.79
0.12
2.91
0.80
0.56
Upper
legs
Inner
2.88
2.18
0.08
9.32
2.1
1.6
Lower
legs
Inner
0.16
0.12
0
0.33
0.11
0.086
Hands
0.74
0.71
0.4
1.27
0.53
0.51
Head/
Neck
1.72
1.47
0.7
3.58
1.2
1.1
Total
Dermal
13.21
9.69
9.4
7.1
Respiratory
0.0022
0
0
0.016
0.0016
0
mg/
lb
ai
=
Exposure
(mg)
÷
1.4
lb
ai
20
Calculation
of
Daily
Exposures:
Assumptions:
1)
An
average
worker
weighs
60
kg
for
dermal
risk
assessment
and
70
kg
for
inhalation
exposure
and
has
standard
body
surface
areas
and
respiration
rates
as
presented
in
the
Pesticide
Assessment
Guidelines
(OPPTS
875
Group
A
test
guidelines).
2)
Examination
of
the
Census
of
Agriculture
data
for
Kansas
yielded
a
median
farm
sizes
of
in
the
100
to
249
acre
range.
Three
other
wheat
producing
states
(North
Dakota,
Washington,
and
Montana)
had
median
farm
sizes
in
the
250
to
499
acre
range.
A
farm
size
of
500
acres
was
assumed.
Workers
were
assumed
to
treat
and
plant
enough
seed
for
250
Acres
per
day,
yielding
a
short
term
exposure
scenario.
3)
Workers
are
assumed
to
wear
the
same
clothing
as
those
participating
in
the
study.
Typical
clothing
consists
of
a
long
sleeved
shirt,
long
pants,
and
chemical
resistant
gloves.
4)
Wheat
is
planted
at
a
rate
of
120
pounds
of
seed
per
acre
and
each
bushel
of
seed
weighs
60
pounds
(Hanson,
A.
A.
(Ed)
(1989)
Practical
Handbook
of
Agricultural
Science.
CRC
Press,
Inc.,
Boca
Raton,
FLA.)
and
BEAD
report.
5)
While
the
application
rate
varies
somewhat
for
various
types
of
seeds,
the
application
rate/
farm
size
is
considered
typical
for
lindane
seed
treatment
products.
Amount
of
seed
treated
per
8
hour
day:
Seed
treated
(lbs)
=
100
A/
day
x
120
lbs
seed/
A
l
=
12000
lb
seed/
day
Amount
of
lindane
handled
per
day:
Lbs
ai
handled
per
day
=
2
oz/
bushel
x
0.1875
x
200
bushels
seed/
day
x
1
lb/
16
oz
=
4.7
lbs
ai/
day
21
Estimation
of
Exposure
(manual
seed
treatment):
Dermal:
Dermal
Exposure
(mg/
kg/
day)
=
9.4
mg/
lb
ai
x
4.7
lbs
ai/
day
÷
60
kg
x
0.1
=
0.074
mg/
kg/
day
Respiratory:
Respiratory
Exposure
(mg/
kg/
day)
=
0.0016
mg/
lb
ai
x
12
lbs
ai/
day
÷
70
kg
=
0.00011
mg/
kg/
day
The
resulting
Dermal
MOE
is:
MOED
=
1.2
mg/
kg/
day
÷
0.074
mg/
kg/
day
=
16
The
resulting
Inhalation
MOE
is:
MOEI
=
0.13
mg/
kg/
day
÷
0.00011
mg/
kg/
day
=
1200
22
APPENDIX
B
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
Date:
April
23,
2002
MEMORANDUM
SUBJECT:
LINDANE:
REVISION
OF
EXPOSURE
ASSESSMENT
FOR
COMMERCIAL
SEED
TREATMENT
PLANT
WORKER
(MRID
45200002,
DP
Barcode
D282419)
(Excerpt)
FROM
David
Jaquith
Reregistration
Action
Branch
4
Health
Effect
Division
(7509C)
TO:
Rebecca
Daiss
Reregistration
Branch
4
Health
Effect
Division
(7509C)
2.2
Revised
Exposure
and
Risk
Estimates
HED
has
reevaluated
the
estimates
of
exposure
and
risk
from
treatment
of
wheat
and
canola
seed
with
lindane
using
median
unit
dermal
and
inhalation
exposures
provided
in
the
HELIX
289FS
Study.
Unit
exposures
used
for
this
assessment
are
summarized
in
Table
2.
Unit
exposure
data
from
the
HELIX
study
are
presented
in
detail
in
Appendix
A.
Table
2.
Unit
Dermal
and
Inhalation
Exposures
of
Workers
During
Seed
Treatment
and
Handling
of
Treated
Seed
1
Median
Unit
Dermal
and
Inhalation
Exposures
Treater
Closed
Transfer
Chemical
Resistant
coveralls
over
long
sleeve
shirt,
long
pants;
chemical
resistant
gloves
Dermal
(n=
17)
0.83
:
g/
lb/
ai
Inhalation
(n=
17)
0.12
:
g/
lb/
ai
Cleaner
Chemical
Resistant
coveralls
over
long
sleeve
shirt,
long
pants;
chemical
resistant
gloves
Dermal
(n=
7)
6.70
:
g/
kg
bw
Inhalation
(n=
7)
1.20
:
g/
kg
bw
Bagger/
Sewer/
Stacker
Chemical
Resistant
coveralls
over
long
sleeve
shirt,
long
pants;
chemical
resistant
gloves
Dermal
chemical
resistant
coveralls
(n=
34)
0.26
:
g/
lb/
ai
Dermal
Cotton/
polyester
coveralls
(n=
19)
0.30
:
g/
lb/
ai
Table
2.
Unit
Dermal
and
Inhalation
Exposures
of
Workers
During
Seed
Treatment
and
Handling
of
Treated
Seed
1
Median
Unit
Dermal
and
Inhalation
Exposures
23
Inhalation
(n=
53)
0.06
:
g/
lb/
ai
Forklift
Operator
cotton/
polyester
coveralls
over
long
sleeve
shirt,
long
pants;
chemical
resistant
gloves
Dermal
(n=
12)
0.08
:
g/
lb/
ai
Inhalation
(n=
12)
0.008
:
g/
lb/
ai
1
Commercial
Seed
Treatment
Plant
Worker
Exposure
Study
with
Helix
289FS
Seed
Treatment
on
Canola
(MRID
452000
02)
The
application
rate
in
the
HELIX
study
was
400
gm
thiamethoxam/
100
kg
seed
(0.88
lb/
220000
lb
seed).
The
throughput
of
seed
of
7000
kg/
hr
(15400
lb/
hr),
6800
kg
/hr(
14960
lb/
hr),
5000
kg/
hr
(11000
lb/
hr),
5000
kg/
hr
(11000
lb/
hr),
10000
kg/
hr
(22000
lb/
hr)
for
sites
1
to
5,
respectively.
The
following
assumptions
were
used
to
estimate
exposure:
6)
The
throughput
of
seed
for
both
wheat
and
canola
is
22000
lb/
per
hour
or
176000
lbs
per
8
hour
day.
7)
The
application
rate
for
wheat
is
0.043
lb
ai
per
hundred
weight
of
seed.
The
application
rate
for
canola
is
1.5
lb
(high
end)
and
0.75
lb
(low
end)
ai
per
hundredweight
of
seed.
3)
Pounds
handled
per
day
for
wheat:
lbs
handled
per
day
wheat
=
176000
lbs/
day
x
0.043
÷
100
lbs
=
76
lbs/
day
lbs
handled
per
day
canola
(high
end)
=
176000
lbs/
day
x
1.5
÷
100
lbs
=
2640
lbs/
day
lbs
handled
per
day
canola
(low
end)
=
176000
lbs/
day
x
0.75
÷
100
lbs
=
1320
lbs/
day
4)
Median
unit
dermal
and
inhalation
exposures
were
used
based
on
data
distribution.
5)
Worker
body
weight
for
dermal
exposure
=
60
kg
(female
body
weight
used
for
developmental
endpoint)
Worker
body
weight
for
inhalation
exposure
=
70
kg
24
APPENDIX
C
Date:
April
24,
2002
MEMORANDUM
SUBJECT:
REVISION
OF
EXPOSURE
ASSESSMENT
FOR
PLANTING
OF
SEED
TREATED
WITH
LINDANE
DP
BARCODE
D282418,
MRID
42251901
(Excerpt)
FROM
David
Jaquith
Reregistration
Action
Branch
4
Health
Effect
Division
(7509C)
TO:
Becky
Daiss
Reregistration
Branch
4
Health
Effect
Division
(7509C)
THRU
Susan
Hummel,
Senior
Scientist
Reregistration
Branch
4
Health
Effects
Division
(7509C)
2.0
CONCLUSIONS
HED
has
reevaluated
the
estimates
of
exposure
and
risk
from
planting
of
wheat
and
canola
seed
with
lindane
using
a
study
specifically
addressing
this
scenario
rather
than
using
PHED
as
a
model
for
planting
seeds.
Using
an
oral
NOAEL
of
1.2
mg/
kg/
day
to
assess
dermal
risk
and
an
inhalation
NOAEL
of
0.13
mg/
kg/
day
the
MOEs
are
:
25
Estimation
of
Dermal
and
Respiratory
Exposures
or
Risksof
Workers
Planting
Wheat
and
Canola
Seed
Treated
with
Lindane
Dermal
Exposure
(mg/
kg/
day)
Respiratory
Exposure
(mg/
kg/
day)
MOE
Dermal
Respiratory
Wheat
0.0013
0.00011
920
1200
Canola
0.0015
0.00013
800
1000
Examination
of
the
data
from
the
revised
assessment,
derived
from
a
planting
study
(not
included
in
PHED)
and
the
previous
assessment
from
PHED
indicates
that
there
are
a
large
number
of
non
detect
samples
in
both
of
the
data
sets.
Since
the
original
PHED
derived
estimates,
which
separated
loading
from
planting
showed
large
numbers
of
non
detects
for
the
planting
function,
it
is
evident
that
the
loading
contributes
the
majority
of
the
exposure
and
that
the
actual
planting
task
contributes
relatively
little
to
the
total
exposure.
3.0
CALCULATION
OF
EXPOSURES
In
order
to
estimate
the
exposures
of
workers
planting
seed
treated
with
lindane
a
number
of
assumptions
regarding
amount
of
seed
planted
and
other
parameters
were
required.
6)
It
is
assumed
that
250
acres
of
wheat
or
canola
can
be
planted
in
a
day
(2).
7)
An
average
worker
has
a
body
weight
of
60
kg
(a
change
from
the
previous
assessment
due
to
changes
in
the
toxicological
parameters)
for
dermal
assessment.
A
weight
of
70
kg
is
used
for
inhalation
assessments.
8)
Wheat
is
planted
at
a
rate
of
120
lbs
of
seed
per
acre.
Canola
is
planted
at
a
rate
of
4
lbs
seed
per
acre.
9)
The
application
rate
of
lindane
on
wheat
seed
is
0.68
oz/
cwt
(0.043
lb/
cwt).
For
canola
the
rate
is
23.3
oz/
cwt
(1.5
lb
ai/
cwt).
See
Appendix
B.
10)
The
dermal
absorption
of
lindane
is
10
percent
(1).
3.1
Exposure
Assessment
for
Wheat
Amount
of
lindane
handled
per
day:
26
Lbs
ai/
day
=
250
A/
day
x
120
lb
seed/
A
x
0.043
lb
ai/
100
lbs
seed
=
12.9
lb
ai/
day
The
resulting
dermal
exposure
using
arithmetic
mean
values
from
Appendix
A
is:
Dermal
Exposure
(mg/
kg/
day)
=
0.0597
mg/
lb
ai
x
12.9
lb
ai/
day
x
0.1
(abs)
÷
60
kg
bw
=
0.0013
mg/
kg/
day
The
resulting
dermal
MOE
using
a
NOAEL
of
1.2
mg/
kg/
day
is:
MOE
=
1.2
mg/
kg/
day/
0.0013
mg/
kg/
day
=
920
The
respiratory
exposure
is:
Respiratory
Exposure
(mg/
kg/
day)
=
12.9
lb
ai/
day
x
0.0006
mg/
lb
ai
÷
70
kg
=
0.00011
mg/
kg/
day
The
resulting
respiratory
MOE
using
a
NOAEL
of
0.13
mg/
kg/
day
is:
MOE
=
0.13
mg/
kg/
day/
0.00011
mg/
kg/
day
=
1200
3.1
Exposure
Assessment
for
Canola
Amount
of
lindane
handled
per
day:
Lbs
ai/
day
=
250
A/
day
x
4
lb
seed/
A
x
1.5
lb
ai/
100
lbs
seed
=
15
lb
ai/
day
The
resulting
dermal
exposure
using
arithmetic
mean
values
from
Appendix
A
is:
Dermal
Exposure
(mg/
kg/
day)
=
0.0597
mg/
lb
ai
x
15
lb
ai/
day
x
0.1
(abs)
÷
60
kg
bw
=
0.0015
mg/
kg/
day
The
resulting
dermal
MOE
using
a
NOAEL
of
1.2
mg/
kg/
day
is:
MOE
=
1.2
mg/
kg/
day/
0.0015
mg/
kg/
day
=
800
The
respiratory
exposure
is:
Respiratory
Exposure
(mg/
kg/
day)
=
15
lb
ai/
day
x
0.0006
mg/
lb
ai
÷
70
kg
=
0.00013
mg/
kg/
day
The
resulting
respiratory
MOE
using
a
NOAEL
of
0.13
mg/
kg/
day
is:
27
MOE
=
0.13
mg/
kg/
day/
0.00013
mg/
kg/
day
=
1000
28
| epa | 2024-06-07T20:31:43.077097 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0202-0006/content.txt"
} |
EPA-HQ-OPP-2002-0202-0007 | Supporting & Related Material | "2002-08-14T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
Date:
April
24,
2002
MEMORANDUM
SUBJECT:
REVISION
OF
EXPOSURE
ASSESSMENT
FOR
PLANTING
OF
SEED
TREATED
WITH
LINDANE
FROM
David
Jaquith
Reregistration
Action
Branch
4
Health
Effect
Division
(7509C)
TO:
Becky
Daiss
Reregistration
Branch
4
Health
Effect
Division
(7509C)
THRU
Susan
Hummel,
Senior
Scientist
Reregistration
Branch
4
Health
Effects
Division
(7509C)
Please
find
attached
the
occupational
and
residential
exposure
assessment
for
lindane
DP
BARCODE
D282418
Pesticide
Chemical
Codes:
009001
EPA
Reg
Nos:
EPA
MRID
Nos.:
42251901
PHED:
No
1.0
INTRODUCTION
In
March
2001
HED
provided
an
exposure/
risk
assessment
for
seed
treatment
use
of
lindane
(1).
The
document
included
on
farm
treatments
(using
wheat
as
the
typical
treatment),
planting
the
treated
seed,
and
commercial
seed
treatment
facilities.
The
treatment
of
seeds
using
on
farm
technology
has
not
changed.
The
assessment
of
exposure
during
planting
was
derived
from
PHED
V1.1
using
the
assumption
that
exposure
from
planting
treated
seed
would
be
similar
to
that
received
from
application
of
granular
formulations
of
pesticides.
Since
that
time
HED
has
received
a
study
actually
measuring
exposure
during
planting.
The
seed
planting
exposure
assessment
has
been
reviewed
by
HED
personnel.
The
results
and
review
of
this
study
are
presented
in
Appendix
A.
2.0
CONCLUSIONS
HED
has
reevaluated
the
estimates
of
exposure
and
risk
from
planting
of
wheat
and
canola
seed
with
lindane
using
a
study
specifically
addressing
this
scenario
rather
than
using
PHED
as
a
model
for
planting
seeds.
Using
an
oral
NOAEL
of
1.2
mg/
kg/
day
to
assess
dermal
risk
and
an
inhalation
NOAEL
of
0.13
mg/
kg/
day
the
MOEs
are
:
Estimation
of
Dermal
and
Respiratory
Exposures
or
Risksof
Workers
Planting
Wheat
and
Canola
Seed
Treated
with
Lindane
Dermal
Exposure
(mg/
kg/
day)
Respiratory
Exposure
(mg/
kg/
day)
MOE
Derma
l
Respiratory
Wheat
0.0013
0.00011
920
1200
Canola
0.0015
0.00013
800
1000
Examination
of
the
data
from
the
revised
assessment,
derived
from
a
planting
study
(not
included
in
PHED)
and
the
previous
assessment
from
PHED
indicates
that
there
are
a
large
number
of
non
detect
samples
in
both
of
the
data
sets.
Since
the
original
PHED
derived
estimates,
which
separated
loading
from
planting
showed
large
numbers
of
non
detects
for
the
planting
function,
it
is
evident
that
the
loading
contributes
the
majority
of
the
exposure
and
that
the
actual
planting
task
contributes
relatively
little
to
the
total
exposure.
3.0
CALCULATION
OF
EXPOSURES
In
order
to
estimate
the
exposures
of
workers
planting
seed
treated
with
lindane
a
number
of
assumptions
regarding
amount
of
seed
planted
and
other
parameters
were
required.
1)
It
is
assumed
that
250
acres
of
wheat
or
canola
can
be
planted
in
a
day
(2).
2)
An
average
worker
has
a
body
weight
of
60
kg
(a
change
from
the
previous
assessment
due
to
changes
in
the
toxicological
parameters)
for
dermal
assessment.
A
weight
of
70
kg
is
used
for
inhalation
assessments.
3)
Wheat
is
planted
at
a
rate
of
120
lbs
of
seed
per
acre.
Canola
is
planted
at
a
rate
of
4
lbs
seed
per
acre.
4)
The
application
rate
of
lindane
on
wheat
seed
is
0.68
oz/
cwt
(0.043
lb/
cwt).
For
canola
the
rate
is
23.3
oz/
cwt
(1.5
lb
ai/
cwt).
See
Appendix
B.
5)
The
dermal
absorption
of
lindane
is
10
percent
(1).
3.1
Exposure
Assessment
for
Wheat
Amount
of
lindane
handled
per
day:
Lbs
ai/
day
=
250
A/
day
x
120
lb
seed/
A
x
0.043
lb
ai/
100
lbs
seed
=
12.9
lb
ai/
day
The
resulting
dermal
exposure
using
arithmetic
mean
values
from
Appendix
A
is:
Dermal
Exposure
(mg/
kg/
day)
=
0.0597
mg/
lb
ai
x
12.9
lb
ai/
day
x
0.1
(abs)
÷
60
kg
bw
=
0.0013
mg/
kg/
day
The
resulting
dermal
MOE
using
a
NOAEL
of
1.2
mg/
kg/
day
is:
MOE
=
1.2
mg/
kg/
day/
0.0013
mg/
kg/
day
=
920
The
respiratory
exposure
is:
Respiratory
Exposure
(mg/
kg/
day)
=
12.9
lb
ai/
day
x
0.0006
mg/
lb
ai
÷
70
kg
=
0.00011
mg/
kg/
day
The
resulting
respiratory
MOE
using
a
NOAEL
of
0.13
mg/
kg/
day
is:
MOE
=
0.13
mg/
kg/
day/
0.00011
mg/
kg/
day
=
1200
3.1
Exposure
Assessment
for
Canola
Amount
of
lindane
handled
per
day:
Lbs
ai/
day
=
250
A/
day
x
4
lb
seed/
A
x
1.5
lb
ai/
100
lbs
seed
=
15
lb
ai/
day
The
resulting
dermal
exposure
using
arithmetic
mean
values
from
Appendix
A
is:
Dermal
Exposure
(mg/
kg/
day)
=
0.0597
mg/
lb
ai
x
15
lb
ai/
day
x
0.1
(abs)
÷
60
kg
bw
=
0.0015
mg/
kg/
day
The
resulting
dermal
MOE
using
a
NOAEL
of
1.2
mg/
kg/
day
is:
MOE
=
1.2
mg/
kg/
day/
0.0015
mg/
kg/
day
=
800
The
respiratory
exposure
is:
Respiratory
Exposure
(mg/
kg/
day)
=
15
lb
ai/
day
x
0.0006
mg/
lb
ai
÷
70
kg
=
0.00013
mg/
kg/
day
The
resulting
respiratory
MOE
using
a
NOAEL
of
0.13
mg/
kg/
day
is:
MOE
=
0.13
mg/
kg/
day/
0.00013
mg/
kg/
day
=
1000
REFERENCES
1)
Memorandum
from
D.
Jaquith
(RRB4)
to
S.
Shallal
(RRB4)
titled
"OCCUPATIONAL
AND
RESIDENTIAL
EXPOSURE
ASSESSMENT
AND
RECOMMENDATIONS
FOR
THE
RE
REGISTRATION
ELIGIBILITY
DECISION
DOCUMENT
FOR
LINDANE",
dated
March
16,
2001.
2)
Memorandum
from
S.
Tadayon
(CEB)
to
A.
Khasawinah
(RRB4)
titled
"OCCUPATIONAL
AND
RESIDENTIAL
EXPOSURE
ASSESSMENT
AND
RECOMMENDATIONS
FOR
THE
RE
REGISTRATION
ELIGIBILITY
DECISION
DOCUMENT
FOR
IMAZALIL"
dated
April
15,
2,000.
cc:
Lindane
file
(009001)
R.
Kent
(RRB4/
7509C)
Correspondence
file
D.
Jaquith
(7509C)
APPENDIX
A.
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
March
03,
2002
Memorandum
SUBJECT:
Exposures
of
Workers
to
Isofenphos
During
Planting
of
Oftanol
Treated
Canola
FROM:
Seyed
Tadayon,
Chemist
Chemistry
Exposure
Branch
Health
Effect
Division
(7509C)
TO:
Jeff
Evans,
Biologist
Chemistry
Exposure
Branch
Health
Effect
Division
(7509C)
DP
Barcode:
D281351
EPA
MRID
No:
42251901
Attached
is
a
review
of
the
applicator
exposure
during
planting
of
treated
seed
with
Oftanol®
which
was
submitted
by
Mobay
Inc.
This
review
was
completed
by
Versar,
Inc.
on
February
15,
2002,
under
supervision
of
HED.
It
has
undergone
secondary
review
in
the
HED
and
has
been
revised
to
reflect
Agency
policies.
Executive
Summary
Oftanol®
Technical
is
an
insecticide
incorporated
into
a
seed
coating
material
that
forms
a
hard,
dry,
shell
like
layer
on
the
outside
of
the
canola
seed.
The
purpose
of
this
study
was
to
quantify
inhalation
and
dermal
exposure
to
workers
planting
treated
seed
using
the
active
ingredients
isofenphos.
The
study
met
most
of
the
criteria
specified
in
Subdivision
K
(currently
referred
to
as
Series
875
.1100
and
875.1300
Group
B).
Summary
This
study
was
conducted
in
Domain,
Manitoba.
Oftanol®
Technical
was
applied
to
canola
seeds
prior
to
this
study
at
a
rate
of
12
g
ai
(isofenphos)
per
kg
of
seed.
Four
workers
were
monitored
four
times,
for
a
total
of
16
replicates,
as
they
opened
and
poured
both
the
contents
of
the
treated
seed
bags
(25
kg)
and
fertilizer
into
their
plant
hoppers.
The
workers
then
drove
a
tractor,
pulling
the
planter
around
the
field
planting
between
six
and
eight
pounds
of
seed
per
acre.
The
workers
used
closed
cab
tractors
with
a
ground
speed
ranging
between
5
to
7
mph.
Both
seed
and
fertilizer
traveled
down
a
tube
to
the
ground,
where
they
were
immediately
covered
with
soil
by
a
disc.
Each
replicate
lasted
an
average
of
3.22
hours
and
each
worker
handled
an
average
of
4.33
lbs
active
ingredient
per
replicate
All
workers
wore
long
sleeved
shirts,
coveralls,
and
chemical
resistant
gloves,
in
addition
to
their
normal
clothing.
Air
temperatures
ranged
from
69
o
F
to
82
o
F
and
relative
humidity
ranged
from
30
to
73%.
Exposure
to
the
treated
seed
was
quantified
by
the
following
methods:
a)
Dermal
exposure
was
estimated
by
10
dermal
patches.
Dosimeters
were
attached
to
the
worker's
coverall
at
10
locations:
With
this
arrangement,
the
coveralls
represented
a
single
layer
of
normal
clothing
and
the
inner
dosimeters
collected
the
isofenphos
that
could
reach
the
workers'skin
if
they
were
wearing
only
a
single
layer
of
clothing.
b)
Exposure
to
the
workers'
hands
was
determined
by
the
hand
rinse
method.
c)
Inhalation
exposure
was
monitored
by
attaching
a
quartz
microfiber
(QMA)
filters
in
polystyrene
cassettes
to
the
workers'
lapels.
d)
Cholinesterase
activity
was
monitored
by
collecting
blood
samples.
Exposure
values
for
both
potential
(based
on
exterior
patches)
and
actual
(based
on
interior
patches)
dermal
exposures
was
calculated.
The
Registrant
corrected
all
data
for
field
fortification
recoveries,
including
recoveries
above
90%.
For
those
values
below
the
LOD,
the
Registrant
used
½
the
recovery
corrected
LOD
value.
Versar
only
corrected
data
for
field
fortification
recoveries
less
<90%
and
reported
non
detect
values
as
½
LOD.
Total
potential
dermal
exposures
ranged
from
0.0095
to
1.2369
mg/
lb
ai
handled.
The
primary
body
region
contributors
were
the
lower
arm
(0.1110
mg/
lb
ai
handled)
and
the
lower
leg
(0.0712
mg/
lb
ai
handled).
The
overall
average
total
potential
dermal
exposure
was
0.3326
±
0.3555
mg/
lb
ai
handled.
The
actual
dermal
exposure
estimates
ranged
from
0.0028
to
0.1053
mg/
lb
ai
handled
with
an
overall
average
actual
dermal
exposure
of
0.0296
±
0.0314
mg/
lb
ai
handled.
Total
dermal
exposure
estimates
included
both
actual
dermal
exposures
and
hand
exposures
and
averaged
0.0597
±
0.1001
mg/
lb
ai
handled.
Total
exposure
was
calculated
by
taking
the
sum
of
all
exposure
routes
(dermal
hands,
dermal
body,
and
inhalation).
The
Registrant
calculated
a
geometric
mean
total
exposure
of
0.15
mg/
lb
ai
applied.
Versar's
calculated
total
exposure
is
presented
in
Table
8
and
averaged
0.060
±
0.101
mg/
lb
ai
handled.
Conclusions
Dermal
and
inhalation
exposures
were
assessed
during
the
planting
of
treated
canola
seed.
The
workers
performed
both
loading
of
the
treated
seed
into
seed
hoppers
and
planting
of
the
seed.
Table
1
provides
a
summary
of
the
total
exposure
to
isofenphos
during
loading
and
planting
of
treated
seed,
as
calculated
by
Versar.
Versar's
calculated
average
total
exposure
was
0.060
±
0.101
mg/
lb
ai
handled.
The
geometric
mean
total
exposure,
as
calculated
by
the
Registrant,
to
isofenphos
during
planting
of
treated
canola
seed
was
0.15
mg/
lb
ai
applied.
The
study
author
also
reported
total
exposure
in
mg/
replicate
and
assumed
that
a
worker
is
able
to
complete
three
replicates
per
day.
The
study
author
estimated
an
average
daily
exposure
of
1.9
mg,
but
noted
that
a
worker
would
probably
not
routinely
work
what
is
equivalent
to
three
replicates
per
day
during
the
planting
season
so
that
actual
daily
exposure
would
likely
be
less
than
1.9
mg/
day.
Table
1:
Summary
of
Total
Exposure
to
Oftanol
During
Loading
and
Planting
Treated
Canola.
Replicate
Exposure
(mg/
lb
ai
handled)
Dermal
body
Dermal
hands
Dermal
Total
Inhalation
Inhalation
+
Dermal
Total
1
0.
0731
0.0104
0.0835
0.0011
0.085
2
0.
1053
0.0069
0.1122
0.0018
0.114
3
0.
0033
0.0034
0.0067
0.0002
0.007
4
0.
0053
0.0046
0.01
0.0002
0.01
5
0.
0249
0.0046
0.0295
0.029
6
0.
016
0.0056
0.0216
0.0002
0.022
8
0.
0028
0.0028
0
0.
003
9
0.
0411
0.3333
0.3745
0.0024
0.377
11
0.0108
0.0068
0.0176
0.0004
0.018
13
0.058
0.0043
0.0623
0
0.
062
14
0.0124
0.0051
0.0174
0
0.
017
15
0.0199
0.0032
0.0231
0.0002
0.023
16
0.0117
0.0037
0.0153
0.0002
0.016
Average
0.
0296
0.0327
0.0597
0.0006
0.06
Standard
Deviation
0.101
9
Attachment
Versar
Review
Memo
dated
Febuary
15,
2002
10
Reviewer:
Kelly
McAloon/
Marit
Espevik
Date
February
15,
2002
STUDY
TYPE:
Applicator
Passive
Dosimetry
Study
Using
Patch
Dosimetry,
Hand
Washes,
Inhalation
Monitoring,
and
Cholinesterase
Monitoring.
TEST
MATERIAL:
OFTANOL®
Technical
insecticide,
a
viscous
liquid
material
formulation
containing
90%
isofenphos
as
the
active
ingredient.
SYNONYMS:
1
Methylethyl
2[[
ethoxy[(
1
methylethyl)
amino]
phosphinothioyl]
oxy]
benzoate
(CAS
#
25311
71
1);
Isofenphos
(ISO
E,
BSI);
Isophenphos
(ISO
F)
CITATION:
Author:
V.
C.
Dean
Title:
Exposures
of
Workers
to
Isofenphos
During
Planting
of
Oftanol
Treated
Canola
Seeds
Report
Date:
January
20,
1990
Performing
Organization:
Mobay
Corporation
Corporate
Occupational
and
Product
Safety
Agricultural
Chemicals
Division
P.
O.
Box
4913,
Hawthorn
Rd.
Kansas
City,
MO
64120
Identifying
Codes:
MRID
422519
01;
Report
Number
99799;
SPONSOR:
Mobay
Corporation
Agricultural
Chemicals
Division
Research
&
Development
Department
EXECUTIVE
SUMMARY:
The
purpose
of
this
study
was
to
quantify
inhalation
and
dermal
exposure
of
workers
handling
canola
seed
treated
with
OFTANOL®
Technical,
containing
90%
isofenphos
as
the
active
ingredient.
The
seeds
had
been
treated
with
OFTANOL®
Technical
prior
to
this
study
and
25
kg
bags
of
treated
seed
were
provided
for
this
exposure
study.
The
study
was
conducted
in
Domain,
Manitoba
from
May
16
23,
1989.
Four
workers
were
monitored
four
times,
for
a
total
of
16
replicates,
as
they
loaded
the
treated
seed
into
seed
hoppers
and
drove
tractors,
planting
between
six
and
eight
pounds
of
seed
per
acre.
Each
replicate
lasted
an
average
of
3.22
hours
and
each
worker
handled
an
average
of
4.33
lbs
active
ingredient
per
replicate.
Dermal
exposure
was
estimated
by
handwashes
and
by
dermal
patches
attached
to
the
inner
and
outer
clothing
of
each
worker.
Total
dermal
exposure
was
calculated
by
adding
the
dermal
exposure
to
the
hand
exposure
values.
Inhalation
exposure
was
measured
using
a
conventional
industrial
hygiene
methodology.
The
Registrant
provided
exposure
values
expressed
in
mg/
hr,
mg/
replicate,
and
mg/
lb
ai
applied.
Total
dermal
exposure
to
isofenphos,
determined
by
the
Registrant,
ranged
from
0.076
mg/
lb
ai
applied
to
0.42
mg/
lb
ai
applied.
The
geometric
mean
total
dermal
exposure
was
estimated
as
0.15
mg/
lb
ai
applied.
The
geometric
mean
inhalation
exposure
to
isofenphos
was
estimated
as
0.0003
mg/
lb
ai
applied.
Total
exposure
to
isofenphos
ranged
from
0.076
mg/
lb
ai
applied
to
0.43
mg/
lb
ai
applied
and
the
geometric
mean
was
0.15
mg/
lb
ai
applied.
The
study
author
also
reported
an
average
daily
total
exposure
of
1.9
mg/
day,
assuming
that
a
worker
is
able
to
complete
three
replicates
per
day.
Versar
calculated
exposure
estimates
in
mg/
lb
ai
handled,
as
per
EPA's
request.
Raw
residue
data
were
corrected
using
the
field
fortification
recoveries.
Versar
only
corrected
for
field
recoveries
less
than
90%.
Versar
calculated
a
mean
potential
11
inhalation
exposure
of
0.0006
±
0.0008
mg/
lb
ai
handled.
The
overall
average
dermal
exposure
and
the
average
hand
exposure,
as
calculated
by
Versar,
were
0.0296
±
0.0314
and
0.0327
±
0.0947
mg/
lb
ai
handled,
respectively.
Total
dermal
exposure
was
calculated
as
the
sum
of
the
overall
dermal
exposure
and
hand
exposure
and
averaged
0.0597
±
0.1001
mg/
lb
ai
handled.
Versar
also
calculated
total
exposure
as
the
sum
of
all
exposure
routes.
The
average
total
exposure
was
estimated
0.060
±
0.101
mg/
lb
ai
handled.
The
Study
Report
also
included
cholinesterase
monitoring
results.
These
results
show
that
the
isofenphos
exposures
to
the
workers
were
well
within
the
acceptable
limits.
The
greatest
deviations
observed
were
7.7%
in
the
plasma
and
3.7
%
in
the
erythrocytes.
The
study
author
attributed
these
deviations
to
natural
variations.
The
study
met
most
of
the
Series
875.1100
and
875.1300
Guidelines.
The
major
issues
of
concern
were:
(1)
this
study
was
performed
at
only
one
test
site,
(2)
raw
field
data
were
corrected
for
all
recoveries,
even
those
greater
than
90%,
(3)
concurrent
laboratory
fortification
recoveries
were
not
provided
in
the
Study
Report,
(4)
the
limit
of
quantification
was
not
provided
for
any
media,
only
the
limit
of
detection,
(5)
the
analysis
dates
were
not
provided
for
any
of
the
samples
in
this
study
in
order
to
verify
storage
stability
results,
(6)
individual
field
blank
results
were
not
provided
in
the
Study
Report,
(7)
there
was
only
one
field
fortification
level
for
air
filter
samples,
(8)
the
Registrant
used
½
the
recovery
corrected
sample
quantification
limits
for
non
detect
values,
rather
than
½
the
method
limit
of
detection
for
that
media,
(9)
method
validation
recoveries
were
not
provided
for
handwash
samples,
(10)
information
on
the
individuals
who
participated
in
this
study
was
not
provided,
(11)
the
inhalation
methodology
was
calibrated
with
an
airflow
of
1L/
min
instead
of
2L/
min,
(12)
the
Registrant
used
the
inhalation
geometric
mean
for
replicate
5
since
no
sample
was
collected,
(13)
the
Registrant
used
values
slightly
different
from
the
NAFTA
recommended
body
region
surface
areas,
and
(14)
the
Registrant
calculated
face
exposures
from
head
exposures.
COMPLIANCE:
A
signed
and
dated
Data
Confidentiality
statement
was
provided.
The
study
sponsor
waived
claims
of
confidentiality
within
the
scope
of
FIFRA
Section
10(
d)
(1)
(A),
(B),
or
(C).
The
study
sponsor
stated
that
the
EPA
Good
Laboratory
Practice
Standards
(40
CFR
part
160)
did
not
apply
to
the
study.
GUIDELINE
OR
PROTOCOL
FOLLOWED:
A
study
protocol
was
provided
with
the
Study
Report.
OPPTS
Series
875,
Occupational
and
Residential
Exposure
Test
Guidelines,
Group
A:
875.1100
(dermal
exposure),
and
875.1300
(inhalation
exposure)
were
followed
for
the
compliance
review
of
this
study.
I.
MATERIALS
AND
METHODS
A.
MATERIALS
1.
Test
Material:
Formulation:
OFTANOL®
Technical
insecticide
contains
90%
(by
weight)
of
isofenphos
as
the
active
ingredient
(ai).
This
product
is
a
viscous
liquid
material
that
is
used
as
a
seed
treatment.
Lot/
Batch
#
technical:
8
00
5270A
Lot/
Batch
#
formulation:
Not
provided.
Purity
in
technical:
The
OFTANOL®
Technical
was
assayed
during
production
at
91.8%
isofenphos.
CAS
#(
s):
25311
71
1
Other
Relevant
Information:
EPA
Registration
number
is
3125
326.
2.
Relevance
of
Test
Material
to
Proposed
Formulation(
s):
The
product
label
was
not
provided
for
the
test
material
used
in
this
study.
Versar
was
able
to
locate
a
product
label
with
the
same
product
name
as
the
one
used
in
this
study.
.
3.
Packaging:
12
The
packaging
of
the
test
product
was
not
reported
in
the
study.
All
seed
coating
was
performed
prior
to
this
study
and
25
kg
bags
of
treated
seed
were
provided
for
this
study.
B.
STUDY
DESIGN
There
were
3
deviations
to
the
protocol:
(1)
in
addition
to
the
analyses
of
plasma
and
erythrocyte
levels,
whole
blood
levels
were
also
evaluated.
Mobay
Corporation's
cholinesterase
analysis
procedure
includes
whole
blood
and
it
was,
therefore,
routinely
included
in
the
analysis,
(2)
one
blood
sample
was
collected
the
morning
after
a
worker
completed
his
monitored
work
cycle
rather
than
immediately
afterwards,
and
(3)
for
replicate
sampling,
three
of
the
sixteen
replicates
monitored
were
not
included
in
the
data
evaluation.
No
adverse
effects
due
to
these
deviations
were
reported
in
the
Study
Report.
1.
Number
and
type
of
workers
and
sites:
Four
individuals
participated
in
the
study
at
one
test
site,
each
serving
as
a
subject
four
times,
for
a
total
of
sixteen
replicates.
Each
test
subject
was
a
private
grower.
The
number
of
years
of
experience
per
worker
was
not
provided.
Each
participant
signed
an
informed
consent
form
prior
to
the
initiation
of
the
study
after
being
provided
the
proper
information
regarding
the
study,
products
being
used,
and
proper
precautions.
The
seed
treatment
was
performed
on
canola
seed
prior
to
this
study
in
Nisku,
Alberta,
Canada,
from
January
17
19,
1989.
This
study
took
place
in
Domain,
Manitoba
where
the
treated
canola
seeds
were
planted
from
May
16
23,
1989.
2.
Meteorology:
Air
temperatures,
relative
humidity,
and
wind
speed
and
direction
were
reported
for
the
four
sampling
days.
Air
temperatures
ranged
from
69
o
F
to
82
o
F
and
relative
humidity
ranged
from
30
to
73%.
Wind
speed
was
reported
as
gusty
for
the
first
two
sampling
days,
with
wind
speeds
ranging
from
10
30
mph.
Wind
speed
on
the
remaining
two
sampling
days
ranged
from
0
10
mph.
Wind
direction
was
reported
as
variable.
3.
Replicates:
Each
of
the
four
workers
were
monitored
for
four
replicates
as
they
opened
and
poured
both
the
contents
of
the
seed
bags
and
fertilizer
into
their
plant
hoppers.
The
workers
then
drove
a
tractor,
pulling
the
planter
around
the
field
planting
between
six
and
eight
pounds
of
seed
per
acre.
Table
1
presents
a
summary
of
the
hours
worked
and
the
lb
ai
handled
for
all
of
the
replicates.
Table
1.
Summary
of
Replicates
13
Date
Replicates
*
Worker
ID
Hours
Worked
lb
ai
handled
37391
1
A
2.73
1.92
37391
2
A
2.25
2.88
37391
3
B
4.33
5.95
37391
4
B
3.08
4.32
37391
5
C
3.03
4.32
37391
6
C
3.08
3.6
37392
8
D
1.83
4.32
37392
9
A
4.75
5.76
37392
11
B
3.
62
2.
94
37393
13
D
2.
87
4.
62
37393
14
D
2.
58
3.
96
37398
15
C
4.
62
6.
24
37398
16
C
3.
13
5.
46
*
Replicates
7,
10,
and
12
not
used.
4.
Protective
clothing:
All
workers
wore
long
sleeved
65%
polyester/
35%
cotton
work
shirts,
65%
polyester/
35%
cotton
coveralls,
and
chemical
resistant
(nitrile,
Best
No.
730)
gloves,
in
addition
to
their
normal
clothing
(denim
trousers,
cotton
shirts,
boots
or
tennis
shoes,
and
baseball
caps).
The
long
sleeved
shirts,
coveralls
and
caps
were
supplied
by
Mobay
Corporation
and
served
as
attachment
sites
for
dermal
dosimeters.
The
gloves,
also
supplied
by
Mobay
Corporation,
were
used
only
as
protective
equipment.
5.
Planting
method:
Worker
A:
Worker
A
used
an
International
310
Diskall
pulled
by
a
closed
cab
tractor
at
a
ground
speed
of
7
mph.
The
worker
opened
the
bags
of
treated
seed
and
poured
them
into
the
seeder
hopper.
Fertilizer
was
also
loaded
into
a
hopper.
Both
seed
and
fertilizer
dropped
to
the
ground
and
were
immediately
covered
with
soil
by
a
disc.
This
equipment
arrangement
provided
for
a
45
ft
swath.
Worker
B:
Worker
B
used
a
Coop
Implements
G
100
Disker
pulled
by
a
John
Deer
8630
close
cab
tractor
at
a
ground
speed
of
5
mph.
The
worker
cut
the
bags
open
with
a
pocket
knife,
stood
on
the
back
of
the
seeder
and
poured
the
25
kg
bag
of
treated
seed
into
the
trough
of
the
seeder.
Fertilizer
was
also
poured
into
the
seeder.
Both
seed
and
fertilizer
traveled
down
a
tube
to
the
ground,
where
they
were
immediately
covered
with
soil
by
a
disc.
This
equipment
arrangement
provided
for
a
30
ft
swath.
Worker
C:
Worker
C
used
an
Air
System
1502
Concord
seeder,
pulled
by
a
Steiger/
Cougar
1000
closed
cab
tractor
at
a
ground
speed
of
6
mph.
The
Concord
Air
tank
is
attached
to
an
EZZE
On
Cultivator.
The
worker
loaded
the
bags
of
treated
seed
into
the
back
of
a
fertilizer
truck.
The
truck
was
driven
to
the
field
and
poured
into
the
hopper
of
the
seeder.
Fertilizer
was
conveyed
from
the
truck
by
an
auger
to
a
hopper
on
the
seeder.
Both
seed
and
fertilizer
were
conveyed
by
air
up
to
the
planter,
where
they
were
deposited
into
the
soil.
This
equipment
arrangement
provided
for
a
36
ft
swath.
Worker
D:
Worker
D
used
a
Chinook
1203,
pulled
by
a
Steiger
CP
1360
closed
cab
tractor
at
a
ground
speed
of
6
mph.
The
Chinook
1203
has
two
hoppers,
one
for
seed
and
one
for
fertilizer.
The
worker
opened
the
25
kg
bags
of
treated
seed
and
poured
them
into
the
seed
hopper
of
the
Chinook
1203.
Seed
and
fertilizer
traveled
from
the
hoppers
through
tubing
to
the
ground
and
were
deposited
into
the
soil.
This
equipment
arrangement
provided
for
a
40
ft.
swath.
6.
Application
Rate:
14
OFTANOL®
Technical
is
an
insecticide
incorporated
into
a
seed
coating
material
that
forms
a
hard,
dry,
shell
like
layer
on
the
outside
of
the
canola
seed.
According
to
the
study
author,
the
coated
seeds
are
virtually
dust
free,
when
applied
in
this
manner.
The
insecticide
protects
newly
sprouted
canola
plants
against
the
flee
beetle.
OFTANOL®
Technical
was
applied
to
canola
seeds
prior
to
this
study
at
a
rate
of
12
g
ai
(isofenphos)
per
kg
of
seed.
All
of
the
seed
coating
was
done
in
Nisku,
Alberta,
Canada,
from
January
17
19,
1989.
A
product
label
was
not
provided
in
the
Study
Report.
Versar
was
able
to
obtain
a
product
label,
but
the
label
did
not
provide
a
recommended
application
rate.
Since
OFTANOL®
Technical
is
not
registered
in
Canada,
this
study
was
conducted
under
Research
Permit
Sub.
No.
89
007.
7.
Exposure
monitoring
methodology:
Dermal
dosimeters:
Dermal
exposure
was
estimated
by
10
dermal
patches.
Dosimeter
units
consisted
of
a
3
inch
by
3
inch
12
ply
gauge
surgical
sponge
enclosed
in
an
aluminized
paperboard
holder.
Dosimeters
were
attached
to
the
worker's
coverall
at
10
locations:
both
upper
arms,
both
palmar
forearms
three
inches
above
the
wrists,
right
chest
just
above
the
pocket,
left
back
at
the
shoulder
blade,
the
front
of
both
thighs,
and
both
shins.
Each
paperboard
holder
had
a
circular
opening,
5.6
cm
in
diameter,
which
faced
away
from
the
body
to
allow
isofenphos
to
collect
on
the
gauze
sponge.
One
dosimeter
was
also
attached
to
the
worker's
cap
just
above
the
bill
and
a
second
set
of
dosimeters
was
attached
to
the
worker's
clothing
inside
the
coveralls
at
the
following
locations:
both
upper
arms,
both
palmar
forearms,
left
chest,
right
back,
both
thighs,
and
both
shins.
With
this
arrangement,
the
coveralls
represented
a
single
layer
of
normal
clothing
and
the
inner
dosimeters
collected
the
isofenphos
that
could
reach
the
workers'
skin
if
they
were
wearing
only
a
single
layer
of
clothing.
Dosimeters
were
worn
until
the
completion
of
the
monitoring
period,
including
maintenance,
checking
seed
and
fertilizer
levels,
and
changing
sites.
At
the
end
of
the
monitoring
interval,
the
dosimeters
were
removed
from
the
clothing
and
placed
on
a
table.
When
all
the
dosimeters
were
removed,
the
gauze
sponges
were
removed
from
their
paperboard
holders
with
tweezers
and
placed
in
labeled
1
ounce
glass
bottles
which
were
capped
with
polyseal
lined
screw
caps
and
stored
on
dry
ice.
Hand:
Exposure
to
the
workers'
hands
was
determined
by
the
hand
rinse
method.
At
the
end
of
the
monitoring
period,
and
at
intermediate
times
when
hands
would
normally
be
washed,
the
worker's
hands
were
rinsed
using
the
following
procedure:
200
mL
portion
of
absolute
ethanol
was
placed
into
a
42
oz
Whirl
Pak
bag.
The
worker
placed
one
hand
into
the
bag
and
the
bag
was
held
tightly
around
the
wrist.
The
hand
and
bag
were
shaken
50
times.
The
ethanol
was
stored
in
the
plastic
bag
and
used
for
subsequent
washes
during
the
monitoring
period
until
the
final
wash.
After
the
final
wash,
it
was
transferred
into
a
800
mL
bottle
for
storage.
Each
hand
was
washed
twice,
for
a
total
of
four
washed
per
replicate.
After
each
of
the
four
washes,
the
solution
was
transferred
into
a
800
mL
bottle
and
vigorously
shaken
50
times.
An
aliquot
of
the
combined
solution
(left
and
right
hand)
was
then
transferred
into
a
one
ounce
labeled
sample
bottle
and
placed
on
dry
ice.
The
remaining
solution
was
discarded.
On
seven
occasions,
the
outsides
of
the
workers'
gloves
were
washed
by
the
same
method
to
provide
a
comparison
of
the
amounts
of
isofenphos
residues
on
hands
and
gloves.
Inhalation:
Inhalation
exposure
was
monitored
using
a
conventional
industrial
hygiene
methodology.
Quartz
microfiber
(QMA)
filters
in
polystyrene
cassettes
were
attached
to
the
workers'
lapels.
Air
was
drawn
through
the
filters
at
approximately
1
L/
min
by
a
portable,
battery
powered
pump
(Gilian
HFS
113A)
attached
to
the
workers'
belt
and
connected
to
the
filter
cassette
with
PVC
tubing.
The
filters
removed
particulates
and
aerosols
containing
isofenphos
from
the
air
during
exposure
sampling.
When
sampling
was
complete,
the
cassette
was
removed,
capped,
placed
in
a
Whirl
Pak
and
stored
on
dry
ice.
Cholinesterase:
Blood
samples
were
collected
by
venipuncture
for
determination
of
cholinesterase
activity
in
the
erythrocyte
and
plasma
fractions.
The
puncture
site
was
washed
thoroughly
with
alcohol
before
sampling
to
sterilize
and
remove
any
isofenphos
contamination
that
could
affect
the
cholinesterase
results.
The
following
schedule
was
used:
1)
Three
pre
exposure
samples
were
collected
to
establish
the
baseline
value
for
each
participant.
They
were
collected
during
the
week
before
planting
began.
Participants
and
Chemargro
Ltd.
technical
personnel
gave
assurances
that
participants
had
not
15
worked
with
cholinesterase
inhibiting
materials
for
a
two
week
period
prior
to
the
baseline
sampling;
and
2)
one
sample
was
collected
at
the
end
of
each
workday,
when
all
work
with
isofenphos
was
completed.
All
samples
were
collected
by
a
locally
licensed
nurse.
They
were
shipped
by
overnight
express
to
the
Mobay
Corporation
Toxicology
Laboratory
in
Stilwell,
Kansas.
The
samples
were
analyzed
the
following
morning,
using
an
automated
modified
Ellman
method.
Results
were
communicated
by
telephone
to
the
study
site
at
mid
day
on
the
day
following
sample
collection.
All
samples
collected
during
mornings
were
stored
in
ice
chests
on
dry
ice
for
approximately
four
hours
until
field
collection
activities
for
the
afternoon
replicates
were
complete.
All
samples
were
then
repacked
on
dry
ice
for
shipping
to
the
Mobay
Corporation
Analytical
Laboratory
in
Kansas
City,
Missouri.
At
the
analytical
laboratory,
the
samples
were
stored
in
freezers
at
7
degrees
Celsius.
8.
Analytical
Methodology:
Extraction
method(
s):
Dermal
Exposure
Patches
15
mL
of
ethanol
was
pipetted
into
sample
vials
and
the
vials
were
recapped.
The
sample
vials
were
placed
in
a
vertical
position
on
a
rotator
and
spun
for
30
minutes
to
ensure
complete
absorption.
Five
mL
of
the
sample
solution
was
pipetted
into
a
clean
15
mL
vial
and
0.5
mL
of
a
0.5%
carbowax
solution
was
added.
The
solvent
was
evaporated
from
the
sample
solution
using
a
stream
of
dry
nitrogen
and
a
heating
block
at
43
o
C.
The
sample
residue
was
reconstituted
by
pipetting
5
mL
of
t
butyl
methyl
ether
(MTBE)
into
the
sample
vial.
The
vial
was
capped
with
a
polyseal
and
shaken
for
30
seconds.
Handrinse
Samples
The
samples
were
shaken
vigorously
and
then
a
portion
was
filtered
using
a
LID/
X
filter.
A
portion
of
the
filtered
solution
was
immediately
transferred
into
an
autosampler
vial
and
the
vial
was
capped.
Air
Filters
Filters
were
transferred
to
0.5
ounce
vials
and
2.0
mL
of
MTBE
was
added.
The
vial
was
sealed
with
a
polyseal
lid
and
gently
swirled
to
wet
the
filter
thoroughly.
The
sample
vial
was
placed
on
a
rotator,
the
rotator
wheel
was
put
in
a
vertical
position,
and
the
vial
was
spun
for
30
minutes
to
ensure
complete
desorption.
Detection
method(
s):
See
Table
2.
16
Table
2.
Summary
of
GC
Chromatographic
and
HPLC
Conditions
Media
Air
Filters
Dermal
pads
Hand
Rinses
Instrument
Varian
Model
3400
Varian
Model
3400
Shimadzu
CR
3A
/Varian
4270
Column
J&
W,
0.541mm
i.
d.
x
15m
length
DB
Wax
fused
silica
capillary
column
with
a
1.0
:
m
film
thickness
J&
W,
0.541mm
i.
d.
x
15m
length
DB
Wax
fused
silica
capillary
column
with
a
1.0
:
m
film
thickness
DuPont
Zorbax
C
8
column,
4.6mm
i.
d.
x
25
cm
length
with
a
0.45
:
m
pore
size
Detector
Nitrogen/
phosphorous
detector
Nitrogen/
phosphorous
detector
Temperatures
Column:
Initial:
100
o
C
Final:
185
o
Injector:
250
o
C
Detector:
300
o
C
Column:
Initital:
100
o
C
Final:
185
o
Injector:
250
o
C
Detector:
300
o
C
Column:
Ambient
Injection
Volume
9
µL
9
µL
100
µL
Retention
Time
Isofenphos:
12.3
min
Isofenphos
oxygen
analog:
13.5
min
Isofenphos:
11.6
min
Isofenphos
oxygen
analog:
12.7
min
Isofenphos:
10.5
min
Isofenphos
oxygen
analog:
3.8
min
Quantitative
Range
0.0025
0.05
ng/
:
L
0.
0025
0.05
ng/
:
L
0.
2
10
ng/
:
L
Method
validation:
The
limit
of
detection
(LOD)
for
air
filters,
gauze
pads,
and
handwash
samples
was
approximately
5ng/
sample,
38
ng/
sample,
and
40
:
g/
sample,
respectively.
For
method
validation,
five
air
filter
samples
were
fortified
at
the
0.2
:
g
level
for
both
isofenphos
and
its
oxygen
analog.
Fourteen
dermal
gauze
samples
were
fortified
at
loadings
of
1.0,
10,
100,
and
1000
:
g
of
isofenphos
under
field
conditions.
Handwash
samples
were
fortified
at
loadings
of
100
and
1000
:
g
using
field
samples.
Method
validation
recoveries
for
the
air
filter
samples
averaged
109.0%
±
3.6%
for
isofenphos
and
94.4%
±
7.3%
for
its
oxygen
analog.
Recoveries
for
the
dermal
gauze
pads
averaged
96.9%±
6%
and
94.2%±
3%,
for
the
1.0
and
1000
:
g
loadings
respectively.
Method
validation
recoveries
for
handwash
samples
were
not
reported
in
the
Study
Report.
Instrument
performance
and
calibration:
According
to
the
Study
Report,
analytical
calibration
standard
curve
data
were
generated
before
and
after
each
set
of
samples
analyzed.
Standard
concentrations
were
chosen
to
bracket
the
sample
concentrations.
Only
concentrations
within
the
validated
range
for
each
media
were
used.
Quantification:
Sample
concentrations
were
calculated
using
the
linear
regression
function
of
a
chromatography
software.
Concentrations
of
isofenphos
in
the
samples
were
determined
directly
from
the
standard
curve.
9.
Quality
Control:
Lab
Recovery:
Laboratory
recoveries
were
not
reported
in
the
Study
Report.
Field
blanks:
Field
blanks
were
collected
for
each
media.
All
values
were
reported
to
be
less
than
the
LOD,
except
for
2
gauze
pad
samples
(0.170
and
11.7
:
g).
Field
recovery:
Handwash
Samples:
Duplicate
handwash
samples
were
fortified
at
200
and
2000
:
g
levels
each
sampling
17
day
at
the
site
by
spiking
a
200
mL
ethanol
portion
with
isofenphos
formulation
solutions.
The
spiked
solutions
were
transferred
into
separate
polyethylene
bags
and
shaken
50
times.
A
portion
of
each
sample
was
transferred
from
the
plastic
bags
into
1
oz
bottles
and
the
bottles
were
capped
with
polyseal
lids
to
simulate
the
procedure
for
collecting
field
samples.
Air
Filters:
Seven
replicate
filter
samples
were
prepared
each
day
by
spiking
37
mm,
acetonitrile
washed
Whatman
QM
A
filters
with
isofenphos
formulation
solution
at
a
loading
of
approximately
0.2
:
g
of
isofenphos.
The
spiked
filters
were
then
placed
in
separate
filter
cassettes.
Each
filter
was
supported
by
a
stainless
steel
screen.
Each
cassette
was
then
sealed
tight
with
a
cellulose
shrink
band
and
the
two
open
ends
were
capped.
To
simulate
the
collection
of
field
samples,
the
caps
of
each
cassette
were
removed
immediately
before
sampling
and
each
filter
unit
was
connected
to
a
sampling
pump
which
had
been
calibrated
to
a
sampling
rate
of
1.0
L
per
minute.
In
addition,
two
blank
filters
were
prepared
at
the
same
time
to
determine
potential
interference
or
contamination
problems.
Dermal
samples:
Seven
replicate
samples
were
generated
at
loading
levels
of
approximately
1.0,
10,
100,
and
1000
:
g
of
isofenphos
to
simulate
anticipated
exposure
levels
for
the
outer
gauze
and
1.0,
and
10
:
g
to
simulate
inner
gauze
pads.
To
spike
the
outer
gauze
pads,
0.5
mL
of
spiking
solutions
containing
approx
2.0,
20,
200,
and
2000
:
g/
mL
of
isofenphos
was
pipetted
onto
separate
gauze
pads.
Once
the
gauze
pads
were
spiked,
the
solvent
was
allowed
to
evaporate.
The
spiked
pads
were
placed
in
direct
sunlight
and
exposed
to
the
environment
for
approximately
the
same
duration
as
the
field
samples.
The
inner
pads
were
spiked
in
the
same
manner,
but
were
placed
under
coverall
material
and
were
not
exposed
to
sunlight.
Field
fortification
recoveries
for
isofenphos
are
presented
in
Table
3.
18
Table
3.
Field
Fortification
Recoveries
for
Isofenphos
Sample
Type
Fortification
Level
(
:
g)
Sampling
Day
Average
Fortification
Recovery
per
Day
(%)
Average
Isofenphos
Recovery
per
Level
(%)
Overall
Average
(%)
Standard
Deviation
Handwash
samples
200
1234
111.3
109.1
97.5
98.3
104.1
102.4
6.
6
2000
1234
108.1
103.4
98.2
92.8
100.6
Filters
0.2
1234
100.1
69.9
86.0
93.9
88.1
88.1
12.2
Outer
Gauze
Pads
1
1234
107.3
73.3
100.8
88.9
92.6
90.1
12.1
10
1234
98.2
73.0
84.2
97.0
88.2
100
1234
87.0
86.1
78.4
110.4
90.9
1000
1234
82.7
89.8
85.4
96.2
88.6
Inner
Gauze
Pads
1
1234
112.7
78.2
84.8
116.3
98.5
96.3
17.1
10
1234
92.9
75.8
92.8
114.6
94.1
Formulation:
The
test
products
used
were
not
characterized
for
this
study.
Storage
Stability:
The
Study
Report
indicated
that
storage
stability
experiments
were
performed
prior
to
the
commencement
of
this
study.
Air
filters:
Approximately
0.2
:
g
isofenphos
and
its
oxygen
analog
were
field
spiked
onto
QM
A
filters.
Air
19
was
pulled
through
the
spiked
filters
at
1.0
L/
min
±
5%
for
3.5
hours.
The
samples
were
then
shipped
to
the
Environmental
Analysis
Laboratory
in
Kansas
City
and
stored
in
the
freezer
at
7
o
C
for
up
to
72
days.
Average
recoveries
ranged
from
91.9%
±
12
to
110%
±
24.
Gauze
pads:
A
field
study
was
conducted
at
Vero
Beach,
Florida,
using
isofenphos
canola
seed
formulation
to
fortify
gauze
pads.
Seven
pads
were
fortified
at
0.990
:
g
isofenphos
and
exposed
to
outdoor
environmental
conditions
for
4.5
hours.
The
samples
were
shipped
to
the
Environmental
Analysis
Laboratory
in
Kansas
City
and
stored
in
the
freezer
for
40
days
prior
to
analysis.
The
average
total
recovery
from
the
gauze
pad
samples
was
104%
±
2%.
Three
indoor
sampling
field
studies
were
also
conducted
at
a
seed
coating
facility
in
Nisku,
Alberta,
Canada.
Gauze
pads
were
fortified
with
isofenphos
canola
seed
formulation
and
exposed
to
the
indoor
environment
of
the
seed
coating
facility
for
8
hours.
The
samples
were
shipped
to
the
Environmental
Analysis
Laboratory
in
Kansas
City
and
stored
for
up
to
159
days.
Average
recoveries
ranged
from
94.0%
±
1.7%
to
118%
±
4%.
Hand
Rinses:
The
study
author
reported
an
average
storage
recovery
of
110%
±
5%
for
storing
samples
of
isofenphos
in
absolute
ethanol
at
a
100
:
g
loading
for
117
days
at
7
o
C.
The
study
author
also
reported
average
recoveries
for
storing
samples
spiked
with
203
or
2031
:
g
isofenphos
at
7
o
C
for
158
days
of
112%
±
1%
and
110%
±
3%,
respectively.
10.
Relevancy
of
Study
to
Proposed
Use:
The
study
monitored
workers
performing
their
normal
duties
during
planting
of
treated
canola
seed.
II.
RESULTS
AND
CALCULATIONS:
A.
EXPOSURE
CALCULATIONS:
The
study
author
provided
exposure
values
expressed
as
mg/
replicate,
mg/
hour,
and
mg/
lb
ai
applied
for
both
dermal
and
inhalation
exposure.
The
total
amount
of
isofenphos
recovered
from
the
air
filters
was
divided
by
the
total
volume
of
air
sample,
multiplied
by
the
respiration
rate
and
hours
worked
per
replicate
to
provide
the
amount
of
isofenphos
in
mg/
replicate.
The
dermal
gauze
pad
values
were
multiplied
by
the
location
area
in
cm
2
to
provide
the
exposure
in
mg
isofenphos
per
location.
These
values
were
summed
to
provide
dermal
gauze
exposure
values
in
mg/
replicate.
Handwash
samples
were
calculated
using
the
same
calculations
as
dermal
exposures,
assuming
an
area
of
410
cm
2
.
Versar
estimated
exposure
values
as
mg/
lb
ai
handled
as
per
EPA's
request.
Versar
calculated
both
potential
(based
on
exterior
patches)
and
actual
(based
on
interior
patches)
dermal
exposures.
The
Registrant
corrected
all
data
for
field
fortification
recoveries,
including
recoveries
above
90%.
For
those
values
below
the
LOD,
the
Registrant
used
½
the
recovery
corrected
LOD
value.
Versar
only
corrected
data
for
field
fortification
recoveries
less
<90%
and
reported
non
detect
values
as
½
LOD.
Inhalation
Exposure
Inhalation
exposures
were
calculated
by
both
the
Registrant
and
Versar
from
the
breathing
zone
air
concentrations
determined
from
the
amount
of
isofenphos
found
on
the
air
sampling
filters
and
the
volume
of
air
sample.
A
moderate
workrate
respiratory
rate
of
0.029
m
3
/min
was
assumed
by
the
Registrant
for
the
duration
of
the
sampling
period.
Versar
used
the
NAFTA
recommended
inhalation
rate
of
0.029
m
3
/min
for
moderate
activities.
According
to
the
Registrant's
calculations,
the
geometric
mean
of
the
inhalation
exposure
was
0.0003
mg/
lb
ai
with
a
geometric
standard
deviation
of
3.7.
Since
no
sample
was
collected
for
replicate
5,
the
Registrant
used
the
geometric
mean
of
all
inhalation
exposures
as
the
value
for
replicate
5
in
their
calculations.
Table
4
provides
the
Versar
calculated
potential
inhalation
exposures.
The
average
exposure
was
0.0006
±
0.0008
mg/
lb
ai
handled.
Potential
Dermal
Exposure
Potential
dermal
exposure
estimates
were
calculated
by
extrapolating
values
from
exterior
patches
to
the
total
surface
area
of
the
appropriate
region.
The
Registrant
did
not
report
potential
dermal
exposures,
although
exterior
dermal
patches
were
analyzed
and
raw
data
were
reported
in
the
Study
Report.
Versar
calculated
potential
dermal
estimates
for
each
region
of
the
20
body
using
the
exterior
patches
(see
Table
5).
The
total
surface
area
of
the
exposed
surfaces
of
the
dermal
patches
was
24.63
cm
2
.
Versar
used
the
default
NAFTA
surface
areas
to
calculate
the
potential
dermal
exposure
for
each
body
region.
Total
potential
dermal
exposures
ranged
from
0.0095
to
1.2369
mg/
lb
ai
handled.
The
primary
body
region
contributors
were
the
lower
arm
(0.1110
mg/
lb
ai
handled)
and
the
lower
leg
(0.0712
mg/
lb
ai
handled).
The
overall
average
total
potential
dermal
exposure
was
0.3326
±
0.3555
mg/
lb
ai
handled.
Actual
Dermal
Exposure
Actual
dermal
exposure
estimates
were
calculated
by
extrapolating
patch
values
from
interior
patches
to
the
total
surface
area
of
the
appropriate
region.
The
Registrant
extrapolated
these
values
using
recommended
surface
area
estimates
found
in
the
EPA
Pesticide
Registration
Guidelines,
Subdivision
U,
Applicator
Exposure.
The
surface
area
of
the
exposed
surfaces
of
the
dermal
patches
was
24.63
cm
2
.
For
actual
dermal
exposure
to
the
head,
the
Registrant
used
the
interior
head
patch
value
multiplied
by
a
penetration
factor
of
0.13.
This
factor
was
calculated
from
the
gauze
dosimeter
data
by
dividing
the
amount
on
an
inner
dosimeter
by
the
amount
on
the
adjacent
outer
dosimeter,
in
every
case
where
both
dosimeters
had
measurable
amounts.
The
Registrant
reported
total
dermal
exposure
as
the
sum
of
the
values
for
covered
skin,
head
and
neck,
and
hands.
The
Registrant
calculated
hand
exposures
assuming
an
exposed
area
of
410
cm
2
and
followed
the
same
calculations
as
those
used
for
dermal
exposure.
According
to
the
Registrant's
calculations,
hand
exposures
ranged
from
0.059
to
0.42
mg/
lb
ai
applied,
with
an
average
hand
exposure
of
0.11
mg/
lb
ai
applied.
Versar's
calculated
hand
exposures
are
reported
in
Table
6.
These
exposures
ranged
from
0.003
to
0.333
mg/
lb
ai
handled.
The
overall
average
hand
exposure
was
0.033
±
0.095
mg/
lb
ai
handled.
The
Registrant
calculated
a
geometric
mean
total
dermal
exposure
of
0.15
mg/
lb
ai
applied.
Versar
calculated
actual
dermal
estimates
for
each
region
of
the
body
using
the
interior
patches
(except
for
the
head)
(see
Table
7).
Versar
used
the
default
NAFTA
surface
areas
to
calculate
the
actual
dermal
exposure
for
each
body
region.
The
actual
dermal
exposure
estimates
ranged
from
0.0028
to
0.1053
mg/
lb
ai
handled
with
an
overall
average
actual
dermal
exposure
of
0.0296
±
0.0314
mg/
lb
ai
handled.
Total
dermal
exposure
estimates
included
both
actual
dermal
exposures
and
hand
exposures
and
averaged
0.0597
±
0.1001
mg/
lb
ai
handled.
Total
Exposure
Total
exposure
was
calculated
by
taking
the
sum
of
all
exposure
routes
(dermal
hands,
dermal
body,
and
inhalation).
The
Registrant
calculated
a
geometric
mean
total
exposure
of
0.15
mg/
lb
ai
applied.
Versar's
calculated
total
exposure
is
presented
in
Table
8
and
averaged
0.060
±
0.101
mg/
lb
ai
handled.
21
III
DISCUSSION
A.
LIMITATIONS
OF
THE
STUDY:
The
study
met
most
of
the
Series
875.1100
and
875.1300
Guidelines.
The
major
issues
of
concern
were:
(1)
this
study
was
performed
at
only
one
test
site,
(2)
raw
field
data
were
corrected
for
all
recoveries,
even
those
greater
than
90%,
(3)
concurrent
laboratory
fortification
recoveries
were
not
provided
in
the
Study
Report,
(4)
the
limit
of
quantification
was
not
provided
for
any
media,
only
the
limit
of
detection,
(5)
the
analysis
dates
were
not
provided
for
any
of
the
samples
in
this
study
in
order
to
verify
storage
stability
results,
(6)
individual
field
blank
results
were
not
provided
in
the
Study
Report,
(7)
there
was
only
one
field
fortification
level
for
air
filter
samples,
(8)
the
Registrant
used
½
the
recovery
corrected
sample
quantification
limits
for
non
detect
values,
rather
than
½
the
method
limit
of
detection
for
that
media,
(9)
method
validation
recoveries
were
not
provided
for
handwash
samples,
(10)
information
on
the
individuals
who
participated
in
this
study
was
not
provided,
(11)
the
inhalation
methodology
was
calibrated
with
an
airflow
of
1L/
min
instead
of
2L/
min,
(12)
the
Registrant
used
the
inhalation
geometric
mean
for
replicate
5
since
no
sample
was
collected,
(13)
the
Registrant
used
values
slightly
different
from
the
NAFTA
recommended
body
region
surface
areas,
and
(14)
the
Registrant
calculated
face
exposures
from
head
exposures.
B.
CONCLUSIONS:
Dermal
and
inhalation
exposures
were
assessed
during
the
planting
of
treated
canola
seed.
The
workers
performed
both
loading
of
the
treated
seed
into
seed
hoppers
and
planting
of
the
seed.
Table
8
provides
a
summary
of
the
total
exposure
to
isofenphos
during
loading
and
planting
of
treated
seed,
as
calculated
by
Versar.
Versar's
calculated
average
total
exposure
was
0.060
±
0.101
mg/
lb
ai
handled.
The
geometric
mean
total
exposure,
as
calculated
by
the
Registrant,
to
isofenphos
during
planting
of
treated
canola
seed
was
0.15
mg/
lb
ai
applied.
The
study
author
also
reported
total
exposure
in
mg/
replicate
and
assumed
that
a
worker
is
able
to
complete
three
replicates
per
day.
The
study
author
estimated
an
average
daily
exposure
of
1.9
mg,
but
noted
that
a
worker
would
probably
not
routinely
work
what
is
equivalent
to
three
replicates
per
day
during
the
planting
season
so
that
actual
daily
exposure
would
likely
be
less
than
1.9
mg/
day.
22
Table
4.
Potential
Inhalation
(mg/
lb
ai
handled)
Based
on
Residue
Levels
Found
on
Air
Filters.
Replicate
Residue
(
:
g/
sample)
Corrected
Value
(
:
g/
sample)
b
Replicate
length
(min)
Volume
of
air
sampled
(L)
Concentration
(mg/
m
3
)
c
lb
ai
handled
Respiration
Rate
(m
3
/min)
Inhalation
exposure
(mg/
lb
ai
handled)
d
1
0.
0664
0.0754
164
164
0.00046
1.92
0.029
0.00114
2
0.
1530
0.1737
135
135
0.00129
2.88
0.029
0.00175
3
0.
0339
0.0385
260
286
0.00013
5.95
0.029
0.00017
4
0.
0289
0.0328
185
203.5
0.
00016
4.32
0.029
0.00020
6
0.
0219
0.0249
185
203.5
0.
00012
3.60
0.029
0.00018
8
a
0.0050
110
107.8
0.
00002
4.32
0.029
0.00002
9
0.
2260
0.1793
285
107.8
0.
00166
5.76
0.029
0.00239
11
0.0608
0.0482
217
238.7
0.
00020
2.94
0.029
0.00043
13
a
0.
0050
172
189.2
0.
00001
4.62
0.029
0.00001
14
a
0.
0050
155
170.5
0.
00001
3.96
0.029
0.00002
15
0.0426
0.0454
277
304.7
0.
00015
6.24
0.029
0.00019
16
0.0460
0.0490
188
206.8
0.
00024
5.46
0.029
0.00024
Mean
0.0006
Geometric
Mean
0.0002
Standard
Deviation
0.0008
Coefficient
of
Variance
(%)
138.58
a
Residue
was
not
detected.
Therefore,
½
the
LOD
(0.
005
:
g/
sample)
was
used.
b
Corrected
for
average
field
fortification
recovery
(88.1%)
c
Concentration
(mg/
m
3
)
=
(Residue
(
:
g/
sample)
x
0.001)/(
sample
volume
(L)
x
m
3
/1000L)
d
Exposure
(mg/
lb
ai
handled)
=
[(
Concentration
(mg/
m
3
)
x
Respiration
rate
(m
3
/min)
x
replicate
length
(min)]/
lb
ai
handled
23
Table
5.
Potential
Dermal
Exposure
(mg/
lb
ai
handled)
Based
on
Exterior
Patches
Replicate
Residues
(ug/
cm
2
)
a
Body
Region
Exposure
(mg/
lb
ai
handled)
c
Head
Back
Chest
Upper
Arm
Lower
Arm
Upper
Leg
Lower
Leg
lb
ai
applied
Head
(1300
cm
2
)
Back
(3550
cm
2
)
Chest
(3550
cm
2
)
Upper
Arm
(2910
cm
2
)
Lower
Arm
(1210
cm
2
)
Upper
Leg
(382
cm
2
)
Lower
Leg
(2380
cm
2
)
Total
1
0.
008
0.007
0.016
0.026
0.333
0.510
0.069
1.92
0.0054
0.1306
0.0302
0.0388
0.2096
0.1014
0.0856
0.6015
2
0.
041
0.007
0.229
0.107
1.473
0.327
0.096
2.88
0.0185
0.0856
0.2828
0.1085
0.6188
0.0434
0.0794
1.2369
3
0.
001
b
0.001
b
0.014
0.017
0.140
0.353
0.093
5.95
0
0.
005
0.009
0.0083
0.0284
0.0227
0.0373
0.1101
4
0.
001
b
0.001
b
0.001
b
0.011
0.029
0.294
0.037
4.32
0
0.
006
0
0.
0077
0.0083
0.026
0.0201
0.0693
5
0.
008
0.006
0.147
0.003
0.190
0.308
0.519
4.32
0.0025
0.05
0.1211
0.002
0.0531
0.0272
0.2861
0.5421
6
0.
020
0.001
b
0.097
0.013
0.043
0.179
0.161
3.6
0.
0071
0.008
0.0961
0.0103
0.0143
0.019
0.1066
0.2609
8
0.
001
b
0.001
b
0.001
b
0.001
b
0.007
0.001
b
0.001
b
4.32
0
0.
006
0
0.
001
0.002
0
0
0.0103
9
0.
050
0.024
0.217
0.074
0.353
0.522
0.036
5.76
0.0113
0.1491
0.1339
0.0373
0.0742
0.0346
0.0148
0.4552
11
0.010
0.001
b
0.001
b
0.007
0.038
0.073
0.035
2.94
0.0044
0.009
0
0.
0072
0.0158
0.01
0.028
0.0751
13
0.008
0.008
0.073
0.029
1.469
0.327
0.183
4.62
0.0021
0.0608
0.0565
0.0184
0.3847
0.027
0.0941
0.6437
14
0.001
b
0.001
b
0.001
b
0.001
b
0.001
0.004
0.001
b
3.96
0
0.
007
0
0.
001
0
0
0
0.
0095
15
0.008
0.006
0.026
0.047
0.143
0.184
0.299
6.24
0.0017
0.0321
0.0133
0.022
0.0278
0.0113
0.1139
0.2222
16
0.001
b
0.001
b
0.014
0.001
b
0.024
0.127
0.134
5.46
0
0.
005
0.009
0
0.
0053
0.009
0.0585
0.0877
Average
0.012
0.005
0.064
0.026
0.326
0.247
0.128
4.33
0.0042
0.0427
0.0581
0.0202
0.111
0.0255
0.0712
0.3326
Standard
Deviation
0.3555
a
Residue
(
:
g/
cm
2
)
=
Residue
(
:
g/
sample)/
Patch
surface
area
(24.63
cm
2
)
b
Residue
was
not
detected.
Therefore,
½
the
LOD
(0.
038
:
g/
sample)
was
used.
c
Body
Region
Exposure
(mg/
lb
ai)=
(Exposure
(
u
g/
cm
2
)
x
Body
Region
(cm
2
)/
lb
ai
applied)
x
0.001
24
Table
6.
Summary
of
Hand
Exposure
(mg/
lb
ai
handled)
based
on
Hand
Washes
Replicate
Residue
both
hands
(
:
g/
sample
)
lb
ai
handled
Hand
exposure
(
:
g
/lb
ai
handled)
Hand
exposure
(mg/
lb
ai
handled)
1
0.
33333333333
1.92
10.4
0.
010
2
0.
33333333333
2.88
6.9
0.
007
3
0.
33333333333
5.95
3.4
0.
003
4
0.
33333333333
4.32
4.6
0.
005
5
0.
33333333333
4.32
4.6
0.
005
6
0.
33333333333
3.60
5.6
0.
006
9
1920
5.76
333.3
0.
333
11
0.33333333333
2.94
6.8
0.
007
13
0.33333333333
4.62
4.3
0.
004
14
0.33333333333
3.94
5.1
0.
005
15
0.33333333333
6.24
3.2
0.
003
16
0.33333333333
5.46
3.7
0.
004
Mean
0.033
Geometric
Mean
0.007
Standard
Deviation
0.095
Coefficient
of
Variance
(%)
289.98
a
Residue
value
not
detected.
Therefore,
½
the
LOD
(40
:
g/
sample)
was
used.
Table
7.
Actual
Dermal
Exposure
(mg/
lb
ai
handled)
Based
on
Interior
Patches
(except
for
Head)
25
Replicate
Residues
(ug/
cm
2
)
a
Body
Region
Exposure
(mg/
lb
ai
handled)
c
Neck
b
Head
Back
Chest
Upper
Arm
Lower
Arm
Upper
Leg
Lower
Leg
lb
ai
applied
Neck
b
Head
(1300
cm
2
)
Back
(3550
cm
2
)
Chest
(3550
cm
2
)
Upper
Arm
(2910
cm
2
)
Lower
Arm
(1210
cm
2
)
Upper
Leg
(382
cm
2
)
Lower
Leg
(2380
cm
2
)
Total
1
0.
023
0.008
0.001
0.001
0.001
0.081
0.033
0.004
1.92
0.002
0.005
0
0
0
0.05
0.007
0.004
0.073
2
0.
236
0.041
0.001
0.022
0.006
0.076
0.036
0.004
2.88
0.0122
0.0185
0
0.
03
0
0.03
0.005
0.003
0.1053
30.
0150.
0010.
0010.
0010.
0010.
0010.
0160.
0015.
95000
0
0
00.
00100
40.
0020.
0010.
0010.
0010.
0010.
0060.
0130.
0014.
32000
0
0
00.
00100.
01
50.
1540.
0080.
0010.
0010.
0010.
0170.
0240.
0154.
320.
0050.
0030
0
0
00.
0020.
0080.
025
60.
0980.
0200.
0010.
0010.
0010.
0010.
0040.
0033.
60.
0040.
0070
0
0
000.
0020.
016
8
0.
0015
0.001
0.001
0.001
0.001
0.001
0.001
0.001
4.32
0
0
0
0
0
0000
9
0.
241
0.030
0.001
0.014
0.003
0.020
0.061
0.012
5.76
0.006
0.0113
0
0
0
00.
0040.
0050.
041
11
0.0015
0.010
0.001
0.001
0.001
0.004
0.010
0.001
2.94
0
0.
004
0
0
0
00.
00100.
011
13
0.081
0.008
0.016
0.003
0.016
0.030
0.059
0.029
4.62
0.003
0.002
0.01
0
0.
01
0
0.005
0.0152
0.058
14
0.0015
0.001
0.005
0.001
0.001
0.001
0.010
0.009
3.96
0
0
0
0
0
00.
0010.
0050.
012
15
0.0291
0.008
0.001
0.007
0.001
0.041
0.023
0.009
6.24
0
0.
002
0
0
0
00.
0010.
0030.
02
16
0.0152
0.001
0.001
0.001
0.008
0.003
0.011
0.010
5.46
0
0
0
0
0
000.
0040.
012
Average
0.
0690.
0120.
0020.
0040.
0030.
0220.
0230.
0084.
330.
0030.
0040
0
0
00.
0020.
0040.
03
Standard
Deviation
0.031
a
Residue
(
:
g/
cm
2
)
=
Residue
(
:
g/
sample)/
Patch
surface
area
(24.63
cm
2
)
b
Sum
of
the
calculations
for
both
front
and
back
neck
(Areas:
150
and
110
cm
2
,
respectively)
c
Body
Region
Exposure
(mg/
lb
ai
handled)=
(Exposure
(ug/
cm
2
)
x
Body
Region
(cm
2
)/
lb
ai
applied)
x
0.001
26
Table
8.
Total
Exposure
(mg/
lb
ai
handled)
Replicate
Exposure
(mg/
lb
ai
handled)
Dermal
body
Dermal
hands
Dermal
Total
Inhalation
Inhalation
+
Dermal
Total
1
0.
0731
0.0104
0.0835
0.0011
0.085
2
0.
1053
0.0069
0.1122
0.0018
0.114
3
0.
0033
0.0034
0.0067
0.0002
0.007
4
0.
0053
0.0046
0.01
0.0002
0.01
5
0.
0249
0.0046
0.0295
0.029
6
0.
016
0.0056
0.0216
0.0002
0.022
8
0.
0028
0.0028
0.00002
0.003
9
0.
0411
0.3333
0.3745
0.0024
0.377
11
0.0108
0.0068
0.0176
0.0004
0.018
13
0.058
0.0043
0.0623
0.00001
0.062
14
0.0124
0.0051
0.0174
0.00002
0.017
15
0.0199
0.0032
0.0231
0.0002
0.023
16
0.0117
0.0037
0.0153
0.0002
0.016
Average
0.0296
0.0327
0.0597
0.0006
0.06
Standard
Deviation
0.101
27
_______
___________________________
Name:
Name:
Evaluator
Peer
Reviewer
Occupational
Exposure
Assessment
Section
Occupational
Exposure
Assessment
Section
__________________
____________________
Date
Date
_________________________
Name:
Head,
Occupational
Exposure
Assessment
Section
_________________________
Date
28
Compliance
Checklist
Compliance
with
OPPTS
Series
875,
Occupational
and
Residential
Exposure
Test
Guidelines,
Group
A:
Guidelines,
875.1300
(inhalation),
and
875.1100
(dermal)
is
critical.
The
itemized
checklist
below
describes
compliance
with
the
major
technical
aspects
of
OPPTS
875.1300,
and
875.1100.
875.1300
S
Investigators
should
submit
protocols
for
review
purposes
prior
to
the
inception
of
the
study.
This
criterion
was
probably
met.
3)
Expected
deviations
from
GLPs
should
be
presented
concurrently
with
any
protocol
deviations
and
their
potential
study
impacts.
The
study
sponsor
stated
that
GLP's
did
not
apply
to
this
study.
4)
The
test
substance
should
be
a
typical
end
use
product
of
the
active
ingredient.
This
criterion
was
met.
5)
The
application
rate
used
in
the
study
should
be
provided
and
should
be
the
maximum
rate
specified
on
the
label.
However,
monitoring
following
application
at
a
typical
application
rate
may
be
more
appropriate
in
certain
cases.
It
is
uncertain
whether
this
criterion
was
met.
A
product
label
was
not
provided
in
the
study
and
the
label
obtained
by
Versar
did
not
provide
a
maximum
application
rate.
6)
Selected
sites
and
seasonal
timing
of
monitoring
should
be
appropriate
to
the
activity.
It
is
uncertain
whether
these
criteria
were
met.
The
study
site
was
located
in
Canada
and
the
study
occurred
during
the
month
of
May.
7)
A
sufficient
number
of
replicates
should
be
generated
to
address
the
exposure
issues
associated
with
the
population
of
interest.
For
outdoor
exposure
monitoring,
each
study
should
include
a
minimum
of
15
individuals
(replicates)
per
activity.
This
criterion
was
met.
Four
individuals
participated
in
this
study,
for
a
total
of
16
replicates.
8)
The
quantity
of
active
ingredient
handled
and
the
duration
of
the
monitoring
period
should
be
reported
for
each
replicate.
This
criterion
was
met.
9)
Test
subjects
should
be
regular
workers,
volunteers
trained
in
the
work
activities
required,
or
typical
homeowners.
This
criterion
was
met.
10)
The
monitored
activity
should
be
representative
of
a
typical
working
day
for
the
specific
task
in
order
to
capture
all
related
exposure
activities.
This
criterion
was
met.
11)
When
both
dermal
and
inhalation
monitoring
are
required,
field
studies
designed
to
measure
exposure
by
both
routes
on
the
same
subjects
may
be
used.
This
criterion
was
met.
12)
The
analytical
procedure
must
be
capable
of
measuring
exposure
to
1
µg/
hr
(or
less,
if
the
toxicity
of
the
material
under
study
warrants
greater
sensitivity).
This
criterion
was
met.
13)
A
trapping
efficiency
test
for
the
monitoring
media
chosen
must
be
documented.
This
criterion
was
not
met.
Trapping
efficiency
tests
were
not
documented
for
any
of
the
media
used
in
this
study.
14)
Air
samples
should
also
be
tested
for
breakthrough
to
ensure
that
collected
material
is
not
lost
from
the
medium
during
sampling.
It
is
recommended
that
at
least
one
test
be
carried
out
where
the
initial
trap
contains
10X
the
highest
amount
of
residue
expected
in
the
field.
This
criterion
was
not
met.
There
was
no
mention
of
any
breakthrough
tests
being
run
on
the
air
filters
used
in
the
study.
15)
The
extraction
efficiency
of
laboratory
fortified
controls
is
considered
acceptable
if
the
lower
limit
of
the
95%
confidence
interval
is
greater
than
75%,
unless
otherwise
specified
by
the
Agency.
At
a
minimum,
seven
determinations
should
be
made
at
each
fortification
level
to
calculate
the
mean
and
standard
deviation
for
recovery.
Total
recovery
from
field
fortified
samples
must
be
greater
than
50%
for
the
study.
These
criteria
were
partially
met.
The
number
of
laboratory
fortified
controls
and
types
of
laboratory
controls
were
not
provided
in
the
Study
Report.
29
Field
fortification
results
were
provided
and
all
were
greater
than
50%.
16)
If
trapping
media
or
extracts
from
field
samples
are
to
be
stored
after
exposure,
a
stability
test
of
the
compound
of
interest
must
be
documented.
Media
must
be
stored
under
the
same
conditions
as
field
samples.
Storage
stability
samples
should
be
extracted
and
analyzed
immediately
before
and
at
appropriate
periods
during
storage.
The
time
periods
for
storage
should
be
chosen
so
that
the
longest
corresponds
to
the
longest
projected
storage
period
for
field
samples.
This
criterion
was
met.
A
storage
stability
test
was
conducted.
The
Registrant,
however,
did
not
provide
the
actual
dates
of
analysis.
17)
A
personal
monitoring
pump
capable
of
producing
an
airflow
of
at
least
2
L/
min.
should
be
used
and
its
batteries
should
be
capable
of
sustaining
maximum
airflow
for
at
least
4
hours
without
recharging.
Airflow
should
be
measured
at
the
beginning
and
end
of
the
exposure
period.
This
criterion
was
probably
not
met.
Personal
monitoring
pumps
were
calibrated
to
1
L/
min
and
it
was
not
reported
if
airflow
was
measured
at
the
beginning
and/
or
end
of
the
exposure
period.
18)
Appropriate
air
sampling
media
should
be
selected.
The
medium
should
entrap
a
high
percentage
of
the
chemical
passing
through
it,
and
it
should
allow
the
elution
of
a
high
percentage
of
the
entrapped
chemical
for
analysis.
This
criterion
was
met.
The
study
utilized
personal
air
samplers
containing
air
filters
and
absorption
tubes.
19)
If
exposed
media
are
to
be
stored
prior
to
extraction,
storage
envelopes
made
from
heavy
filter
paper
may
be
used.
The
envelope
must
be
checked
for
material
that
will
interfere
with
analysis.
Unwaxed
sandwich
bags
should
be
used
to
contain
the
filter
paper
envelopes
to
help
protect
against
contamination.
This
criterion
was
probably
met.
The
Registrant
states
that
after
collection
of
the
fiberglass
filters,
the
air
filter
cassettes
were
removed,
capped,
and
place
in
Whirl
Pak
bags.
20)
Personal
monitors
should
be
arranged
with
the
intake
tube
positioned
downward,
as
near
as
possible
to
the
nose
level
of
the
subject.
This
criterion
was
met.
The
cassette
containing
the
air
filter
was
attached
to
the
worker's
lapel.
21)
Field
calibration
of
personal
monitors
should
be
performed
at
the
beginning
and
end
of
the
exposure
period.
It
is
uncertain
whether
this
criterion
was
met.
There
was
no
mention
of
calibration
procedures
in
the
Study
Report.
22)
Field
fortification
samples
and
blanks
should
be
analyzed
for
correction
of
residue
losses
occurring
during
the
exposure
period.
Fortified
samples
and
blanks
should
be
fortified
at
the
expected
residue
level
of
the
actual
field
samples.
Fortified
blanks
should
be
exposed
to
the
same
weather
conditions.
These
criteria
were
met.
The
Registrant
mentioned
that
both
field
fortified
samples
and
field
blanks
were
collected.
23)
Data
should
be
corrected
if
any
appropriate
field
fortified,
laboratory
fortified
or
storage
stability
recovery
is
less
than
90
percent.
This
criterion
was
met.
The
Registrant
corrected
all
data
for
field
recoveries,
even
those
greater
than
90%.
24)
Respirator
pads
should
be
removed
using
clean
tweezers
and
placed
in
protective
white
crepe
filter
paper
envelopes
inside
sandwich
bags.
The
pads
should
be
stored
in
a
chest
containing
ice
until
they
are
returned
to
the
laboratory,
where
they
should
be
stored
in
a
freezer
prior
to
extraction.
This
criterion
was
not
applicable
to
this
study.
25)
Field
data
should
be
documented,
including
chemical
information,
area
description,
weather
conditions,
application
data,
equipment
information,
information
on
work
activity
monitored,
sample
numbers,
exposure
time,
and
any
other
observations.
These
criteria
were
partially
met.
Brief
descriptions
of
the
test
product
used,
the
work
activities
being
monitored,
the
planting
equipment
used,
the
application
rate,
the
location
of
the
study,
and
weather
conditions
were
provided
in
the
Study
Report.
However,
no
information
regarding
the
individuals
used
in
the
study
was
provided.
26)
Analysis
methods
should
be
documented
and
appropriate.
This
criterion
was
met.
27)
A
sample
history
sheet
must
be
prepared
by
the
laboratory
upon
receipt
of
samples.
This
criterion
was
not
met.
875.1100
30
28)
Investigators
should
submit
protocols
for
review
purposes
prior
to
the
inception
of
the
study.
This
criterion
was
probably
met.
29)
Expected
deviations
from
GLPs
should
be
presented
concurrently
with
any
protocol
deviations
and
their
potential
study
impacts.
The
study
sponsor
stated
that
GLP's
did
not
apply
to
this
study.
30)
The
test
substance
should
be
a
typical
end
use
product
of
the
active
ingredient.
This
criterion
was
met.
31)
The
application
rate
used
in
the
study
should
be
provided
and
should
be
the
maximum
rate
specified
on
the
label.
However,
monitoring
following
application
at
a
typical
application
rate
may
be
more
appropriate
in
certain
cases.
It
is
uncertain
whether
this
criterion
was
met.
A
product
label
was
not
provided
in
the
study
and
the
label
obtained
by
Versar
did
not
provide
a
maximum
application
rate.
32)
Selected
sites
and
seasonal
timing
of
monitoring
should
be
appropriate
to
the
activity.
It
is
uncertain
whether
these
criteria
were
met.
The
study
site
was
located
in
Canada
and
the
study
occurred
during
the
month
of
May.
33)
A
sufficient
number
of
replicates
should
be
generated
to
address
the
exposure
issues
associated
with
the
population
of
interest.
For
outdoor
exposure
monitoring,
each
study
should
include
a
minimum
of
15
individuals
(replicates)
per
activity.
This
criterion
was
met.
Four
individuals
participated
in
this
study,
for
a
total
of
16
replicates.
34)
The
quantity
of
active
ingredient
handled
and
the
duration
of
the
monitoring
period
should
be
reported
for
each
replicate.
This
criterion
was
met.
35)
Test
subjects
should
be
regular
workers,
volunteers
trained
in
the
work
activities
required,
or
typical
homeowners.
This
criterion
was
met.
36)
Any
protective
clothing
worn
by
the
test
subjects
should
be
identified
and
should
be
consistent
with
the
product
label.
This
criterion
was
met.
The
protective
clothing
worn
by
the
test
subjects
was
identified
and
was
consistent
with
the
product
label
obtained
by
Versar.
37)
The
monitored
activity
should
be
representative
of
a
typical
working
day
for
the
specific
task
in
order
to
capture
all
related
exposure
activities.
This
criterion
was
met.
38)
Dermal
exposure
pads
used
for
estimating
dermal
exposure
to
sprays
should
be
constructed
from
paper
making
pulp
or
similar
material
(i.
e.,
alpha
cellulose),
approximately
1
mm
thick,
that
will
absorb
a
considerable
amount
of
spray
without
disintegrating.
The
alpha
cellulose
material
should
not
typically
require
preextraction
to
remove
substances
that
interfere
with
residue
analysis.
This
should
be
determined
prior
to
using
the
pads
in
exposure
tests
.This
criterion
is
not
applicable
to
this
study.
39)
Dermal
exposure
pads
used
for
estimating
dermal
exposure
to
dust
formulations,
dried
residues,
and
to
dust
from
granular
formulation
should
be
constructed
from
layers
of
surgical
gauze.
The
pad
should
be
bound
so
that
an
area
of
gauze
at
least
2.5
inch
square
is
left
exposed.
The
gauze
must
be
checked
for
material
that
would
interfere
with
analysis
and
be
preextracted
if
necessary.
These
criteria
were
partially
met.
The
exposure
pads
were
constructed
from
a
surgical
sponge
and
had
a
circular
opening
5.6
cm
(2.2
in)
in
diameter.
It
was
not
stated
whether
the
gauze
was
checked
for
material
that
would
interfere
with
analysis.
40)
A
complete
set
of
pads
for
each
exposure
period
should
consist
of
10
to
12
pads.
If
the
determination
of
actual
penetration
of
work
clothing
is
desired
in
the
field
study,
additional
pads
can
be
attached
under
the
worker's
outer
garments.
Pads
should
be
attached
under
both
upper
and
lower
outer
garments,
particularly
in
regions
expected
to
receive
maximum
exposure.
Pads
under
clothing
should
be
near,
but
not
covered
by,
pads
on
the
outside
of
the
clothing.
This
criterion
was
met.
41)
If
exposed
pads
are
to
be
stored
prior
to
extraction,
storage
envelopes
made
from
heavy
filter
paper
may
be
used.
The
envelope
must
be
checked
for
material
that
will
interfere
with
analysis.
Unwaxed
sandwich
bags
should
be
used
to
contain
the
filter
paper
envelopes
to
help
protect
against
contamination.
This
criterion
was
not
met.
Gauze
pads
were
stored
in
1
ounce
glass
bottles
capped
with
poly
seal
screw
caps
and
stored
on
dry
ice.
31
42)
Hand
rinses
should
be
performed
during
preliminary
studies
to
ensure
that
interferences
are
not
present.
Plastic
bags
designed
to
contain
0.5
gal
and
strong
enough
to
withstand
vigorous
shaking
(i.
e.,
at
least
1
mil
inch
thickness)
should
be
used.
During
preliminary
studies,
plastic
bags
must
be
shaken
with
the
solvent
to
be
used
in
the
study
to
ensure
that
material
which
may
interfere
with
analysis
is
not
present.
It
is
unknown
if
this
criterion
was
met.
The
study
author
made
no
mention
of
preliminary
hand
rinse
studies.
43)
The
analytical
procedure
must
be
capable
of
quantitative
detection
of
residues
on
exposure
pads
at
a
level
of
1
ug/
cm
2
(or
less,
if
the
dermal
toxicity
of
the
material
under
study
warrants
greater
sensitivity).
It
is
unknown
if
this
criterion
was
met.
The
limit
of
quantification
was
not
provided
in
the
study.
The
limit
of
detection
for
exposure
pads
was
reported
as
38
ng/
sample.
44)
The
extraction
efficiency
of
laboratory
fortified
controls
is
considered
acceptable
if
the
lower
limit
of
the
95%
confidence
interval
is
greater
than
75%,
unless
otherwise
specified
by
the
Agency.
At
a
minimum,
seven
determinations
should
be
made
at
each
fortification
level
to
calculate
the
mean
and
standard
deviation
for
recovery.
Total
recovery
from
field
fortified
samples
must
be
greater
than
50%
for
the
study.
These
criteria
were
partially
met.
The
number
of
laboratory
fortified
controls
and
types
of
laboratory
controls
were
not
provided
in
the
Study
Report.
Field
fortification
recovery
results
were
provided
and
all
were
greater
than
50%.
45)
If
the
stability
of
the
material
of
interest
is
unknown,
or
if
the
material
is
subject
to
degradation,
the
investigator
must
undertake
and
document
a
study
to
ascertain
loss
of
residues
while
the
pads
are
worn.
It
is
recommended
that
collection
devices
be
fortified
with
the
same
levels
expected
to
occur
during
the
field
studies.
The
dosimeters
should
be
exposed
to
similar
weather
conditions
and
for
the
same
time
period
as
those
expected
during
field
studies.
These
criteria
were
met.
A
storage
stability
test
was
conducted.
The
Registrant,
however,
did
not
provide
the
actual
dates
of
analysis.
46)
Data
should
be
corrected
if
any
appropriate
field
fortified,
laboratory
fortified
or
storage
stability
recovery
is
less
than
90
percent.
This
criterion
was
met.
The
Registrant
corrected
all
raw
residue
data
for
field
recoveries.
47)
Field
data
should
be
documented,
including
chemical
information,
area
description,
weather
conditions,
application
data,
equipment
information,
information
on
work
activity
monitored,
sample
numbers,
exposure
time,
and
any
other
observations.
These
criteria
were
partially
met.
Brief
descriptions
of
the
test
produce
used,
the
work
activities
being
monitored,
the
planting
equipment
used,
the
application
rate,
the
location
of
the
study,
and
the
weather
conditions
were
provided
in
the
Study
Report.
However,
no
information
regarding
the
individuals
used
in
the
study
was
provided.
48)
A
sample
history
sheet
must
be
prepared
by
the
laboratory
upon
receipt
of
samples.
This
criterion
was
not
met.
32
APPENDIX
B
Comparison
of
Application
Rates
of
Lindane
Among
Registered
Crops
Group
Crop
Ounce
ai/
cwt
Max
Seed
Lb
ai/
acre
Max
Seed
cwt/
acre
Max
Ounce
ai/
acre
Max
Pound
ai/
acre
Root
&
Tuber
Radish
0.53
20
0.2
0.
106
0.0066
Leafy
Veggies
Celery
1.31
2
0.
02
0.
0262
0.0016
Lettuce
1.31
3
0.
03
0.
0393
0.0025
Swiss
1.
31
8
0.08
0.1048
0.0066
Spinach
1.
31
15
0.
15
0.
1965
0.0123
Cereal
Grains
Corn
2
18
0.
18
0.
36
0.
0225
Barley
0.5
96
0.
96
0.
48
0.
0300
Oats
0.6
128
1.28
0.768
0.0480
Rye
0.
5
112
1.12
0.56
0.0350
Soughum
1.13
75
0.75
0.8475
0.0530
Wheat
0.68
120
1.2
0.
816
0.0510
Misc.
Canola
23.3
4
0.04
0.932
0.0583
Brassica
Broccoli
1.91
1.5
0.
015
0.02865
0.0018
Brussels
1.91
1.5
0.
015
0.02865
0.0018
Cabbage
1.91
1.5
0.
015
0.02865
0.0018
Cauli
1.
91
1.
5
0.015
0.02865
0.0018
Collards
1.
91
4
0.04
0.0764
0.0048
Kale
1.91
4
0.
04
0.
0764
0.0048
Kohlrabi
1.91
5
0.
05
0.
0955
0.0060
Mustard
1.91
5
0.
05
0.
0955
0.0060
Source
for
Maximum
Lb
Seed
per
Acre:
Martin,
J.
H.,
W.
H.
Leonard,
and
D.
L.
Stamp,
"Principles
of
Field
Crop
Production,
Third
Edition:,
Macmillan
Publishing
Co.,
Inc.,
1976.
| epa | 2024-06-07T20:31:43.084510 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0202-0007/content.txt"
} |
EPA-HQ-OPP-2002-0202-0008 | Supporting & Related Material | "2002-08-14T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
September
28,
2000
MEMORANDUM
SUBJECT:
Lindane;
P.
C.
Code
009001.
The
HED
Toxicology
Chapter
for
the
Risk
Assessment
for
the
Reregistration
Eligibility
Decision
Document
(RED),
Case
#
818566.
DP
Barcode:
D269338
From:
Suhair
Shallal,
Toxicologist
Reregistration
Branch
4
Health
Effects
Division
(7509C)
Thru:
Sanjivani
Diwan,
Senior
Toxicologist
Reregistration
Branch
4
Health
Effects
Division
(7509C)
and
Susan
V.
Hummel,
Branch
Senior
Scientist
Reregistration
Branch
4
Health
Effects
Division
(7509C)
To:
Suhair
Shallal,
Risk
Assessor
Reregistration
Branch
4
Health
Effects
Division
(7509C)
Attached
is
the
Toxicology
Chapter
for
lindane,
for
purposes
of
issuing
a
Reregistration
Eligibility
Decision
(RED)
Document.
2
LINDANE
PC
Code:
009001
Toxicology
Disciplinary
Chapter
for
the
Reregistration
Eligibility
Decision
Document
Date:
September
28,
2000
TABLE
OF
CONTENTS
1.
0
HAZARDCHARACTERIZATION........................................
4
2.
0
REQUIREMENTS
....................................................
5
3.
0
DATAGAP(
S)
.......................................................
6
4.
0
HAZARDASSESSMENT...............................................
6
4.
1
AcuteToxicity...............................................
6
4.
2
SubchronicToxicity...........................................
6
4.
3
PrenatalDevelopmentalToxicity................................
10
4.
4
ReproductiveToxicity........................................
14
4.
5
ChronicToxicity
............................................
16
4.
6
Carcinogenicity
.............................................
21
4.
7
Mutagenicity
...............................................
23
4.
8
Neurotoxicity
..............................................
24
4.
9
Metabolism................................................
28
5.
0
TOXICITYENDPOINTSELECTION....................................
30
5.
1
SeeSection9.
2for
EndpointSelectionTable.
......................
30
5.
2
DermalAbsorption..........................................
30
5.
3
ClassificationofCarcinogenicPotential
...........................
30
6.
0
FQPACONSIDERATIONS
............................................
31
6.
1
SpecialSensitivitytoInfantsandChildren.........................
31
6.
2
RecommendationforaDevelopmentalNeurotoxicityStudy............
32
7.
0
REFERENCES
......................................................
33
8.
0
APPENDICES.......................................................
36
8.
1ToxicityProfileSummaryTables
................................
37
8.
1.
1AcuteToxicityTable
............................
37
8.
1.
2
Subchronic,
ChronicandOther
ToxicityTables
........
37
Lindane/
September
2000
RED
Toxicology
Chapter
4
1.0
HAZARD
CHARACTERIZATION
Lindane
is
a
moderately
toxic
compound
in
EPA
toxicity
class
II.
Labels
for
products
containing
it
must
bear
the
Signal
Word
WARNING.
It
is
neither
an
eye
nor
dermal
sensitizer.
Some
formulations
of
lindane
are
classified
as
Restricted
Use
Pesticides
(RUP),
and
as
such
may
only
be
purchased
and
used
by
certified
pesticide
applicators.
Lindane
is
no
longer
manufactured
in
the
U.
S.,
and
most
agricultural
and
dairy
uses
have
been
canceled
by
the
EPA
because
of
concerns
about
the
compound's
potential
to
cause
cancer.
The
primary
effect
of
lindane
is
on
the
nervous
system;
as
seen
in
both
acute,
subchronic,
and
developmental
neurotoxicity
studies,
as
well
as,
combined
chronic
and
carcinogenicity
study,
lindane
appears
to
cause
neurotoxic
effects
including
tremors,
convulsions
and
hypersensitivityto
touch.
This
is
further
corroborated
by
the
published
literature
in
which
human
exposure
has
been
seen
to
produce
neurologic
effects.
Lindane
also
causes
renal
and
hepatic
toxicity
via
the
oral,
dermal
and
inhalation
routes
of
exposure
as
seen
in
subchronic,
reproduction
and
chronic
toxicity
studies
in
the
rat.
Indevelopmental
toxicitystudies,
no
developmental
effects
were
seen
at
levels
where
maternal
toxicity
was
evident.
In
the
rat
developmental
study,
the
developmental
effects
(extra
rib
and
total
skeletal
variations)
were
seen
at
dose
levels
(20
mg/
kg/
day)
greater
than
those
that
elicit
maternal
toxicity
(10
mg/
kg/
day).
In
the
reproduction
study,
both
systemic
and
developmental
LOAELs
are
13
mg/
kg;
however
a
qualitative
difference
in
maternal
and
offspring
effects
(reduced
body
weight
of
maternal
animals
and
reduced
viability
and
delayed
maturation
in
pups)
indicates
an
increased
pup
susceptibility
to
exposure
to
lindane.
This
is
further
corroborated
by
a
developmental
neurotoxicity
study
in
which
a
qualitative
and
quantitative
increase
in
susceptibility
is
seen.
At
the
high
dose
(13.
7
mg/
kg/
day)
,
parental
animals
have
a
reduced
body
weight
and
body
weight
gain
while
at
the
mid
dose
(5.6
mg/
kg/
day)
offspring
have
a
reduced
survival
rate,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation
as
compared
to
controls.
The
FQPA
factor
was
therefore
reduced
to
3X.
The
toxicity
endpoints
have
been
selected
by
the
Hazard
Identification
Assessment
Review
Committee
(HIARC,
7/
00)
and
can
be
found
in
Section
8
Appendices.
They
include
acute
and
chronic
reference
doses
(RfDs),
and
short,
intermediate
and
long
term
dermal
and
inhalation
no
observable
adverse
effect
levels
(NOAELs).
A
reassessment
of
the
cancer
classification
will
occur
after
a
review
of
the
new
mouse
carcinogenicity
report
due
in
December
2000.
Currently,
according
to
the
TES
committee
report
(1994),
lindane
has
not
been
classified
by
the
HED
Cancer
Peer
Review
Committee.
The
RfD/
Peer
Review
Committee
(1993)
concluded
that:
"The
mouse
carcinogenicity
data
were
considered
insufficient
because
of
major
deficiencies
associated
with
all
studies
available."
Lindane
however
had
been
previously(
1985)
classified
bythe
Cancer
Assessment
Group
of
the
Office
of
Research
and
Development
as
a
group
B2/
C
carcinogen
based
on
increased
incidence
of
mouse
liver
tumors.
The
upper
bound
slope
of
the
dose
response
as
reported
in
the
memorandum
is
Q1*
=
1.
1
(mg/
kg/
day)
1
.
Lindane
does
not
appear
to
be
mutagenic.
The
available
mutagenicity
studies
are
negative;
they
include
a
dominant
lethal
mutation
assay,
sister
chromatid
exchange
assay
and
mammalian
cell
culture
gene
mutation
in
V79
cells.
IPCS
(1991)
reported
that
lindane
does
not
appear
to
have
Lindane/
September
2000
RED
Toxicology
Chapter
5
mutagenic
potential.
There
is
some
evidence
that
lindane
may
act
as
an
endocrine
disruptor;
further
investigation
is
necessary
to
ascertain
the
relevance
and
impact
of
such
findings
on
public
health.
2.0
REQUIREMENTS
The
requirements
(CFR
158.340)
for
food
use
for
LINDANE
are
in
Table
1.
Table
1.
A
Test
Technical
Required
Satisfied
870.1100
Acute
Oral
Toxicity
.............................
870.1200
Acute
Dermal
Toxicity
...........................
870.1300
Acute
Inhalation
Toxicity
.........................
870.2400
Primary
Eye
Irritation
............................
870.2500
Primary
Dermal
Irritation
.........................
870.2600
Dermal
Sensitization
............................
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
870.3100
Oral
Subchronic
(rodent)
.........................
Oral
Subchronic
(nonrodent)
......................
870.3200
21
Day
Dermal
................................
870.3250
90
Day
Dermal
................................
870.3465
90
Day
Inhalation
...............................
yes
yes
yes
yes
870.3150
yes
yes
870.3700a
Developmental
Toxicity
(rodent)
...................
870.3700b
Developmental
Toxicity
(nonrodent)
................
870.3800
Reproduction
..................................
yes
yes
yes
yes
yes
yes
870.4100a
Chronic
Toxicity
(rodent)
.........................
870.4100b
Chronic
Toxicity
(nonrodent)
......................
870.4200a
Oncogenicity
(rat)
..............................
870.4200b
Oncogenicity
(mouse)
............................
870.4300
Chronic/
Oncogenicity
............................
yes
yes
yes
yes
yes
yes
no
870.5100
Mutagenicity
C
GeneMutation
bacterial
.............
870.5300
Mutagenicity
C
GeneMutation
mammalian...........
870.5915
Mutagenicity
C
Other
GenotoxicEffects
..............
yes
yes
yes
yes
870.6100a
Acute
Delayed
Neurotox.
(hen)
....................
870.6100b
90
Day
Neurotoxicity
(hen)
.......................
870.6200a
Acute
Neurotox.
Screening
Battery
(rat)
..............
870.6200b
90
Day
Neuro.
Screening
Battery
(rat)
...............
870.6300
Develop.
Neuro
................................
no
no
yes
yes
yes
yes
yes
yes
870.7485
General
Metabolism
.............................
870.7600
Dermal
Penetration
.............................
yes
yes
Special
Studies
for
Ocular
Effects
AcuteOral
(rat)
................................
SubchronicOral(
rat)
............................
Six
monthOral
(dog)
............................
no
no
no
A
Use
of
the
new
guideline
numbers
does
not
imply
that
the
new
(1998)
guideline
protocols
were
used.
3.0
DATA
GAP(
S)
A
Mouse
Carcinogenicity
Study
is
expected
in
December
2000.
Lindane/
September
2000
RED
Toxicology
Chapter
6
4.0
HAZARD
ASSESSMENT
4.1
Acute
Toxicity
Adequacy
of
data
base
for
acute
toxicity:
The
data
base
for
acute
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
Lindane
is
a
moderately
toxic
compound
in
EPA
toxicity
class
II.
It
is
neither
an
eye
nor
dermal
sensitizer.
The
vehicle
used
when
administering
lindane
can
determine
its
toxicity.
It
appears
that
oily
solutions
of
lindane
are
more
toxic
than
ones
suspended
in
water.
Clinical
signs
including
convulsions,
spasms
as
well
as
death
have
been
found
to
occur
after
administration
of
lindane.
The
acute
toxicity
data
on
LINDANE
is
summarized
below
in
Table
2.
Table
2.
Acute
Toxicity
Data
on
LINDANE
Guideline
No./
Study
Type
MRID
No.
Results
Toxicity
Category
870.1100
Acute
oral
toxicity
00049330
LD50
88
mg/
kg
males
91
mg/
kg
females
II
870.1200
Acute
dermal
toxicity
00109141
LD50
1000
mg/
kg
males
900
mg/
kg
females
II
870.1300
Acute
inhalation
toxicity
Acc.
263946
LC50
1.56
mg/
L
both
sexes
III
870.2400
Acute
eye
irritation
Acc.
263946
PIS
=
0.6
no
corneal
involvement
irritation
cleared
after
24
hours
III
870.2500
Acute
dermal
irritation
Acc.
263946
PIS
=
0
not
an
irritant
IV
870.2600
Skin
sensitization
Acc.
263946
not
a
sensitizer
NA
4.2
Subchronic
Toxicity
Adequacy
of
data
base
for
subchronic
toxicity:
The
data
base
for
subchronic
toxicity
is
considered
complete
due
to
the
availability
of
chronic
studies
and
subchronic
neurotoxicitystudy.
No
additional
studies
are
required
at
this
time.
Lindane
appears
to
affect
the
liver
and
kidneyin
male
rats
when
administered
through
the
oral,
dermal
or
inhalation
routes
of
exposure.
In
addition,
in
an
oral
neurotoxicity
study,
hypersensitivity
to
touch
and
hunched
posture
were
the
basis
for
a
neurotoxicity
LOAEL
of
28.1
mg/
kg.
870.3100
90
Day
Oral
Toxicity
Rat
The
requirements
for
subchronic
oralstudies
are
satisfied
by
chronic
oral
studies.
See
chronic
oral
section
for
executive
summaries.
Lindane/
September
2000
RED
Toxicology
Chapter
7
870.3100
90
Day
Oral
Toxicity
Mouse
The
requirements
for
subchronic
oral
studies
are
satisfied
by
chronic
oral
studies.
See
chronic
oral
section
for
executive
summaries.
870.3150
Oral
Toxicity
Dog
Chronic
studies
in
two
species,
rat
and
rabbit,
are
available.
See
chronic
oral
section
for
executive
summaries.
870.3200
90
Day
Dermal
Toxicity
B
Rat
EXECUTIVESUMMARY:
Ina
subchronic
dermal
toxicitystudy(
MRID41427601),
groups
of
40
male
and
40
female
New
Zealand
white
rabbits
were
treated
with
lindane
(99.5%
a.
i.)
in
5%
aqueous
carboxymethyl
cellulose
at
doses
of
0,
10,
60,
or
400
mg/
kg/
day.
Due
to
excessive
toxicity
the
high
dose
was
reduced
to
350
mg/
kg/
day
from
week
nine
and
to
320
mg/
kg/
day
from
week
eleven.
Animals
were
treated
by
dermal
occlusion
for
6
hours/
day,
5
days/
week.
Within
each
dose
group,
10
animals/
sex
were
used
for
interim
sacrifice
at
week
6,
20
animals/
sex
were
used
for
the
main
study
and
dosed
for
13
weeks,
and
10
animals/
sex
were
dosed
for
13
weeks
and
allowed
a
6
week
recovery
period.
Tremors
and
convulsions
were
observed
in
high
dose
animals
beginning
after
day
16
in
males
and
after
day
19
in
females.
One
mid
dose
female
displayed
these
clinical
signs
on
day
50
only.
Clinical
signs
of
toxicity
were
not
observed
in
low
dose
animals.
Reactions
at
the
site
of
application
were
not
reported.
In
the
high
dose
group,
17
males
and
8
females
died
prior
to
scheduled
sacrifice.
Deaths
were
first
observed
after
week
5.
All
animals
in
the
control,
low,
and
mid
dose
groups
survived
to
scheduled
sacrifice.
Body
weights
and
body
weight
gains
by
the
low
and
mid
dose
males
and
females
were
similar
to
the
controls
throughout
the
study.
High
dose
males
and
females
began
to
lose
weight
after
the
first
week
of
the
study
resulting
in
absolute
body
weights
3
7%
and
3
10%,
respectively,
lower
than
the
controls
during
the
13
weeks
of
treatment.
During
recovery,
body
weights
of
the
males
remained
3
8%
below
the
controls
while
females
recovered
to
1
3%
lower
than
the
controls.
Body
weight
data
were
not
analyzed
statistically.
Body
weight
loss
by
the
high
dose
groups
correlated
with
generally
reduced
food
consumption
during
treatment.
No
treatment
related
effects
were
observed
on
ophthalmology,
urinalysis,
or
white
blood
cell
parameters.
Alkaline
phosphatase
activity
was
significantly
increased
in
high
dose
animals
at
interim
sacrifice
for
females
(+
34%;
p
0.
05),
and
at
main
study
sacrifice
for
males
(+
44%;
p
0.01)
and
females
(+
53%;
p
0.
01).
High
dose
females
also
had
significantly
increased
glutamyl
transferase
activity
(+
38%;
p
0.
01)
at
main
study
sacrifice.
For
high
dose
males,
significant
(p
0.05
or
0.01)
reductions
in
hemoglobin
(
7%),
RBC
(
8.
6%),
and
PCV
(
5.
7%)
were
observed
at
main
study
sacrifice.
These
red
cell
parameters
were
comparable
to
the
controls
after
recovery.
Red
cell
parameters
in
females
were
not
affected.
At
main
study
sacrifice,
high
dose
males
and
females
had
slightly
increased
absolute
kidney
weights
and
significantly
(p
0.01)
increased
relative
kidney
weights
as
compared
with
the
controls.
Lindane/
September
2000
RED
Toxicology
Chapter
8
Absolute
and
relative
kidney
(left
and
right)
weights
were
104
106%
and
112
114%,
respectively,
for
males
and
105
106%
and
115
116%,
respectively,
for
females.
High
dose
females
also
had
significantly
(p
0.01)
increased
absolute
(+
27.01
to
27.24%)
and
relative
(+
30.53
to
44.985)
liver
weights
at
both
interim
and
main
study
sacrifice
which
remained
slightly
(+
13
to
17.31%;
n.
s.)
elevated
after
recovery.
Relative
liver
weights
were
significantly
(+
36.77%;
p
0.01)
increased
for
high
dose
males
at
main
study
sacrifice.
Absolute
adrenal
weights
(left
and
right)
were
significantly
(p
0.05
or
0.01)
increased
at
main
study
sacrifice
for
mid
dose
males
(+
19.5
to
23.4%),
high
dose
males
(+
40.5
to
46.3%),
and
high
dose
females
(+
33
to
34%).
Relative
adrenal
weights
were
increased
(p
0.05
or
0.01)
+19
to
21.6%
for
mid
dose
males
and
+46
to
56.9%
for
high
dose
males
and
females.
Following
the
recovery
period,
organ
weights
of
the
treated
groups
were
similar
to
the
control
group.
No
treatment
related
gross
or
histopathological
lesions
were
observed
in
the
kidneys,
adrenals,
or
skin.
The
incidence
and
severity
of
centrilobular
hypertrophy
of
the
liver
was
increased
in
mid
and
high
dose
males
and
females
at
the
interim,
main,
and
recovery
sacrifice
times.
At
both
the
interim
and
main
sacrifices,
centrilobular
hypertrophy
was
observed
in
20%
of
mid
dose
males,
25
30%
of
mid
dose
females,
80
100%
of
high
dose
males
and
73
90%
of
high
dose
females.
Following
recovery
this
lesion
was
seen
in
30%
and
40%
of
mid
dose
males
and
females,
respectively,
and
in
50%
and
29%
of
high
dose
males
and
females,
respectively.
Therefore,
the
dermal
toxicity
LOAEL
is
>400
mg/
kg/
day
and
the
dermal
toxicity
NOAEL
is
not
identified.
The
systemic
toxicity
LOAEL
is
60
mg/
kg/
day
based
on
histopathological
lesions
of
the
liver
in
males
and
females
and
increased
adrenal
weights
of
males.
The
systemic
toxicity
NOAEL
is
10
mg/
kg/
day.
This
study
is
classified
as
Acceptable/
guideline
and
does
satisfy
the
guideline
requirements
for
a
repeated
dose
dermal
study
(82
2)
in
rabbits.
870.3465
90
Day
Inhalation
B
Rat
EXECUTIVE
SUMMARY:
In
a
subchronic
inhalation
toxicity
study
(Accession
No.
255003),
lindane
(99.9%
a.
i.,
Batch
no.
79044/
174)
was
administered
by
inhalation
to
groups
of
12
male
and
12
female
Wistar
rats
at
nominal
concentrations
of
0,
0.02,
0.10,
0.50,
or
5.0
mg/
m
3
,6
h/
day
for
90
days.
Additional
control
and
high
concentration
groups,
12
rats/
sex,
were
treated
for
90
days
and
allowed
to
recover
for
6
weeks
before
sacrifice.
Analytically
measured
atmospheric
concentrations
were
0,
0.02,
0.12,
0.60,
and
4.
54
mg/
m
3
,
respectively.
The
arithmetic
mean
particle
size
of
the
aerosol
was
1.
11±
0.39
µm
and
the
geometric
mean
was
1.
03±
1.45
µm.
Lindane
was
detected
in
the
brain,
liver,
fat,
and
serum
of
all
exposed
rats.
The
chemical
accumulated
in
fat
with
levels
reaching
127,120
µg/
g
and
58,
260
µg/
g
in
high
dose
females
and
males,
respectively.
After
the
recovery
period,
traces
of
lindane
were
still
detectable
in
the
tissues.
All
rats
survived
to
scheduled
sacrifice.
"Slight"
diarrhea
and
piloerection
were
observed
in
all
males
and
females
exposed
to
the
highest
concentration,
but
the
time
to
onset
and
duration
were
Lindane/
September
2000
RED
Toxicology
Chapter
9
not
included.
No
exposure
related
effects
were
noted
for
bodyweight
gain,
food
consumption,
water
consumption,
or
urinalysis
parameters.
Although
hematology
parameters
did
not
appear
to
be
affected
by
treatment,
no
individual
animal
data
were
included
and
the
statistics
could
not
be
verified.
Clinical
chemistry
results,
especially
for
Na
+
,K
+
,andCa
++
,
were
highly
variable.
Cytochrome
p
450
in
males
and
females
exposed
to
5
mg/
m
3
was
338%
and
174%,
respectively,
of
the
control
values
after
90
days,
but
similar
to
the
control
levels
after
the
recovery
period.
Bone
marrow
myelograms
from
animals
exposed
to
5
mg/
m
3
showed
significantly
(p
0.05)
increased
reticulocytes
(+
108%),
stemcells
(+
31%),
and
myeloblasts
(+
33%)
in
males,
and
increased
reticulocytes
(+
55)
in
females,
and
decreased
(
45%)
lymphocytes
in
females.
However,
these
changes
in
bone
marrow
cannot
be
definitively
attributed
to
treatment
since
bone
marrow
from
the
other
exposed
groups
was
not
assayed.
Males
exposed
to
5
mg/
m
3
had
significantly
(p
0.05
or
0.01)
increased
absolute
(+
7.8%
to
+11.7%)
and
relative
(+
19.1%
to
19.2%)
kidney
weights
as
compared
with
the
controls.
Absolute
and
relative
kidney
weights
in
the
males
exposed
to
0.
5
mg/
m
3
were
increased
by
8
9.8%
and
6.
98.2
respectively.
Although
not
statistically
significant,
the
increases
in
kidney
weights
for
these
groups
were
considered
biologically
significant.
After
the
recovery
phase,
kidney
weights
from
the
exposed
males
were
similar
to
the
controls.
In
females
exposed
to
5
mg/
m
3
absolute
and
relative
kidney
weights
were
increased
(p
0.05)
by
9.2
9.9%
and
7.
9
8.
2%,
respectively,
as
compared
with
the
controls.
In
high
dose
males,
absolute
liver
weights
were
not
affected,
but
relative
liver
weights
were
slightly
(6.
9%)
higher
than
the
controls.
For
females
exposed
to
the
highest
dose,
absolute
and
relative
liver
weights
were
12.2%
and
11.0%
higher,
respectively,
than
the
controls.
No
differences
in
absolute
and
relative
liver
weights
were
noted
between
the
exposed
and
control
groups
after
the
recovery
period.
Kidney
lesions
in
males
exposed
to
0,
0.
02,
0.10,
0.50,
or
5.0
mg/
m
3
,
were
observed
in
17%,
0,
25%,
83%
and
82%,
respectively,
of
the
animals.
These
lesions
included
cloudy
swelling
of
the
tubule
epithelia,
dilated
renal
tubules
with
protein
containing
contents,
and
proliferated
tubules.
After
the
recovery
phase,
only
cloudy
swelling
of
the
tubule
epithelia
was
observed
in
two
control
animals
and
one
high
concentration
animal.
Therefore,
the
systemic
toxicity
LOAEL
is
0.50
mg/
m
3
(0.
13
mg/
kg)
based
on
transient
microscopic
lesions
in
the
kidney
and
increased
kidney
weights
of
male
rats.
The
systemic
toxicity
NOAEL
is
0.
1
mg/
m
3
(0.
025
mg/
kg).
This
study
is
considered
Acceptable/
guideline
and
satisfies
the
requirement
for
a
subchronic
inhalation
toxicity
study
in
rats
[82
4].
870.6200
Subchronic
oral
neurotoxicity
B
Rat
See
Section
4.
8
Neurotoxicity
for
Executive
Summary
Lindane/
September
2000
RED
Toxicology
Chapter
10
4.3
Prenatal
Developmental
Toxicity
Adequacy
of
data
base
for
Prenatal
Developmental
Toxicity:
The
data
base
for
prenatal
developmental
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
Lindane
is
not
considered
teratogenic
when
administered
orally
or
subcutaneously.
Developmental
NOAELs
were
found
to
be
at
levels
equal
to
or
greater
than
maternal
NOAELs,
except
in
the
Developmental
Neurotoxicity
Study.
The
neurotoxicity
LOAEL
was
5.
6
mg/
kg/
day
(NOAEL
is
1.2
mg/
kg/
day)
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation
compared
to
a
maternal
toxicity
LOAEL
of
13.7
mg/
kg/
day
(NOAEL
is
5.6
mg/
kg/
day)
based
on
decreased
body
weight
gains,
decreased
food
consumption,
and
increased
reactivity
to
handling.
870.3700a
Prenatal
Developmental
Toxicity
Study
Rat
EXECUTIVE
SUMMARY:
In
a
developmental
toxicity
study
(MRID
42808001),
20
presumed
pregnant
CFY(
derived
fromCharles
River
CD)
rats
per
group
were
administered
technical
lindane
(purity
not
given;
Batch
No.
6801/
403)
by
gavage
in
0.5%
carboxymethyl
cellulose
at
doses
of
0,
5,
10,
and
20
mg/
kg/
day
on
gestation
days
(GD)
6
15,
inclusive.
On
GD
20,
dams
were
sacrificed
by
CO2
,
subjected
to
gross
necropsy,
and
all
fetuses
examined
externally.
Approximately
one
third
of
each
litter
was
processed
for
visceral
examination
and
the
remaining
two
thirds
was
processed
for
skeletal
examination.
Deaths
of
two
high
dose
dams
were
attributed
bythe
authors
to
treatment
although
the
cause
of
death
was
not
reported.
No
treatment
related
clinical
signs
of
toxicity
were
observed
in
any
animal.
Body
weight
gains
and
food
consumption
by
the
mid
and
high
dose
groups
were
decreased
during
the
treatment
interval
as
compared
with
the
controls.
Body
weight
gains
by
the
mid
and
high
dose
dams
were
70%
and
46%,
respectively,
of
the
control
values
during
GD
6
14.
Food
consumption
by
the
mid
and
high
dose
groups
was
72%
of
the
control
level
during
GD
7
10
and
92%
and
65%,
respectively,
during
GD
11
14.
It
should
be
noted
that
data
were
not
available
for
the
entire
dosing
interval
and
that
statistical
analyses
were
not
provided
for
these
data.
Maternal
necropsy
was
unremarkable.
Organ
weights
were
similar
between
the
treated
and
control
groups.
Therefore,
the
maternal
toxicity
LOAELis
10
mg/
kg/
day
based
on
reduced
body
weight
gain
and
food
consumption.
The
maternal
toxicity
NOAEL
is
5
mg/
kg/
day.
No
significant
differences
were
observed
between
the
control
group
and
the
treated
groups
for
number
of
corpora
lutea,
number
of
implantation
sites,
live
fetuses/
dam,
pre
and
postimplantation
losses,
fetal
body
weights,
or
fetal
sex
ratios.
No
treatment
related
effects
were
found
at
external
or
visceral
examination
of
the
fetuses.
The
percentage
of
litters
in
the
control,
low,
mid,
and
high
dose
groups
containing
fetuses
with
extra
(14th)
ribs
was
12.7,
21.0,
31.7,
and
40.6%
(p
0.05),
respectively.
The
total
incidences
of
litters
containing
fetuses
with
skeletal
variants
were
43.4,
52.7,
59.5,
and
68.
0%
(p
0.01),
respectively.
Although
the
response
rates
in
the
high
dose
group
for
extra
ribs
and
total
variants
are
Lindane/
September
2000
RED
Toxicology
Chapter
11
within
the
upper
limit
of
historical
control
data,
they
were
considered
treatment
related
due
to
the
dose
related
manner
of
increase.
Therefore,
the
developmental
toxicity
LOAEL
is
20
mg/
kg/
day
based
on
increases
in
extra
ribs
and
total
skeletal
variants;
a
trend
for
increases
in
these
endpoints
at
the
lower
doses
is
recognized.
The
developmental
toxicity
NOAEL
is
10
mg/
kg/
day.
Although,
this
study
was
conducted
prior
to
implementation
of
current
guidelines
but
is
considered
sufficient
for
the
purpose
for
which
it
was
intended.
This
study
is
classified
as
Acceptable/
nonguideline
and
satisfies
the
requirements
for
a
developmental
toxicity
study
(83
3a)
in
rats.
Several
deficiencies
were
noted
in
the
conduct
of
this
study:
percent
purity
of
the
test
article
wast
not
given,
less
than
20
litters/
group
were
available,
dosing
solutions
were
not
analyzed
for
concentration,
stability,
or
homogeneity,
and
much
of
the
individual
animal
data
were
not
included.
EXECUTIVE
SUMMARY:
In
a
developmental
toxicity
study
(MRID
00062656),
groups
of
presumed
pregnant
Sprague
Dawley
rats
were
administered
lindane
(purity
not
given;
Lot
No.
36346)
by
subcutaneous
injection
in
corn
oil
(1
ml/
kg)
at
doses
of
0,
5,
15,
or
30
mg/
kg/
day
on
gestation
days
(GD)
6
15,
inclusive.
On
GD
19,
dams
were
sacrificed
and
the
fetuses
removed.
Approximately
one
third
of
the
fetuses
from
each
litter
were
sectioned
and
examined
for
visceral
malformations/
variations.
The
remaining
two
thirds
of
each
litter
were
"examined
externally"
and
processed
and
examined
for
skeletal
malformations/
variations.
Two
high
dose
animals
died
prematurely.
Clinical
signs
of
toxicity,
including
tremors,
convulsions,
urine
stains,
excit
ability,
and
anorexia,
were
reported
for
one
high
dose
animal.
However,
it
was
not
possible
to
correlate
clinical
signs
with
death
since
individual
animal
data
were
not
included.
No
other
clinical
signs
of
toxicity
were
reported.
Body
weight
gains
by
the
mid
and
high
dose
dams
were
76%
and
23%,
respectively,
of
the
control
levels
during
the
treatment
interval
with
both
groups
attaining
statistical
significance
(p
0.
05).
Overall
body
weight
gain
by
the
highdose
group
was
69%
(p
0.05)
of
the
controls.
Food
consumption
by
the
high
dose
group
was
47%
of
the
control
level
during
GD
6
11.
Body
weight
gains
by
the
low
dose
group
and
food
consumption
for
the
low
and
mid
dose
groups
were
similar
to
the
controls
throughout
the
study.
Gross
necropsy
data,
other
than
uterine
data,
for
the
dams
were
not
provided.
Therefore,
the
maternal
toxicity
LOAEL
is
15
mg/
kg/
day
based
on
decreased
body
weight
gain.
The
maternal
toxicity
NOAEL
is
5
mg/
kg/
day.
No
treatment
related
effects
were
observed
between
the
control
group
and
the
treated
groups
for
number
of
corpora
lutea,
number
of
implantation
sites,
live
fetuses/
dam,
pre
and
postimplantation
losses,
fetal
body
weights,
or
fetal
crown
rump
lengths.
No
treatment
related
visceral
or
skeletal
malformations/
variations
were
observed
in
any
of
the
fetuses.
Results
of
external
examination
were
not
reported.
Therefore,
the
developmental
toxicity
NOAELis
>30
mg/
kg/
day
and
the
developmental
toxicity
LOAEL
was
not
identified.
Lindane/
September
2000
RED
Toxicology
Chapter
12
This
study
is
classified
as
Unacceptable/
nonguideline
and
does
not
satisfy
the
requirements
for
a
developmental
toxicity
study
(83
3a)
in
rats.
Several
deficiencies
were
noted
in
the
conduct
of
this
study:
the
subcutaneous
route
is
not
the
preferred
method
of
administration,
percent
purity
of
the
test
article
was
not
given,
dosing
solutions
were
not
analyzed
for
concentration,
stability,
or
homogeneit
y,
less
than
20
litters/
group
were
available
for
evaluation,
and
much
of
the
individual
maternal
and
fetal
data
were
not
included.
However,
this
data
may
be
used
as
supplemental
information.
870.3700b
Prenatal
Developmental
Toxicity
Study
Rabbit
EXECUTIVE
SUMMARY:
In
a
developmental
toxicity
study
(MRID
42808002),
13
presumed
pregnant
NewZealand
white
rabbits
per
group
were
administered
lindane
(puritynot
given;
Batch
No.
6801/
403)
by
gavage
in
0.
5%
carboxymethyl
cellulose
at
doses
of
0,
5,
10,
or
20
mg/
kg/
day
on
gestation
days
(GD)
6
18,
inclusive.
On
GD
29,
dams
were
sacrificed,
subjected
to
gross
necropsy,
and
all
fetuses
examined
for
visceral
and
skeletal
malformations/
variations.
Data
from
external
examination
of
the
fetuses
was
not
included.
All
does
survived
to
scheduled
sacrifice.
No
treatment
related
clinical
signs
of
toxicity
were
observed.
Maternal
body
weight
and
food
consumption
were
similar
between
the
treated
and
control
groups.
Gross
necropsy
was
unremarkable.
Organ
weights
were
similar
between
the
treated
and
control
groups.
Therefore,
the
maternal
toxicity
NOAEL
is
>20
mg/
kg/
day
and
the
maternal
toxicity
LOAEL
was
not
identified.
No
treatment
related
effects
were
observed
in
any
dose
group
for
number
of
corpora
lutea,
number
of
implantation
sites,
live
fetuses/
dam,
pre
and
post
implantation
losses,
fetal
body
weights,
or
fetal
sex
ratios.
No
treatment
related
visceral
or
skeletal
malformations/
variations
were
observed
in
any
of
the
fetuses.
Therefore,
the
developmental
toxicity
NOAELis
>20
mg/
kg/
day
and
the
developmental
toxicity
LOAEL
was
not
identified.
This
study
is
classified
as
Unacceptable/
not
upgradable
and
does
not
satisfy
the
requirements
for
a
developmental
toxicity
study
(83
3b)
in
rabbits.
Maternal
and
developmental
toxicity
LOAELs
were
not
identified
and
the
highest
dose
did
not
approach
the
limit
dose.
Therefore,
dose
selection
was
considered
inadequate.
Doses
were
based
on
the
results
of
a
subcutaneous
study
in
the
rabbit
(MRID
00062658)
which
is
not
a
valid
method
for
selecting
doses
for
an
oral
study.
Several
other
deficiencies
were
noted
in
the
conduct
of
this
study:
percent
purity
of
the
test
article
was
not
given,
dosing
solutions
were
not
analyzed
for
concentration,
stability,
or
homogeneity,
and
much
of
the
individual
animal
data
were
not
included.
EXECUTIVE
SUMMARY:
In
a
developmental
toxicity
study
(MRID
00062658),
15
presumed
pregnant
New
Zealand
white
rabbits
per
group
following
artificial
insemination
were
administered
lindane
(purity
and
Batch
No.
not
given)
by
subcutaneous
injection
in
corn
oil
Lindane/
September
2000
RED
Toxicology
Chapter
13
(0.
5
ml/
kg)
at
doses
of
0,
5,
15,
or
45
mg/
kg/
day
on
gestation
days
(GD)
6
18,
inclusive.
Due
to
excessive
toxicity,
the
high
dose
was
reduced
to
30
mg/
kg/
day
after
GD
9.
On
GD
29,
dams
were
sacrificed,
subjected
to
gross
necropsy,
and
all
fetuses
examined
for
visceral
and
skeletal
malformations/
variations.
Data
from
external
examination
of
the
fetuses
was
not
included.
One
mid
dose
damaborted
and
died
on
GD21
and
14/
15
high
dose
animals
died
between
GD10
and
26.
The
high
dose
group
was
then
discontinued
due
to
excessive
mortality.
Decreased
activity
and
immobilized
rear
quarters
were
observed
in
the
mid
dose
group
(frequency
and
number
affected
not
reported).
No
clinical
signs
of
toxicity
were
observed
in
the
low
dose
group.
During
GD
6
20,
does
in
the
mid
dose
group
had
a
body
weight
loss
of
126.7
g
as
compared
with
a
body
weight
gain
of
218.0
g
by
the
controls.
Body
weight
loss
was
accompanied
by
"markedly
lower"
food
consumption
by
the
mid
dose
animals.
Body
weight
changes
and
food
consumption
for
the
low
dose
group
were
similar
to
the
controls
throughout
the
study.
It
appeared
that
does
in
the
mid
and
high
dose
group
had
differences
in
the
texture
of
the
liver,
however,
data
from
gross
necropsy
were
difficult
to
interpret
due
to
poor
copy
quality
of
the
original
report.
Therefore,
the
maternal
toxicity
LOAEL
is
15
mg/
kg/
day
based
on
clinical
signs
of
toxicity,
death,
and
reduction
in
body
weight.
The
maternal
toxicity
NOAEL
is
5
mg/
kg/
day.
No
treatment
related
effects
were
observed
between
the
control
group
and
the
treated
groups
for
number
of
corpora
lutea,
number
of
implantation
sites,
live
fetuses/
dam,
pre
and
postimplantation
losses,
fetal
body
weights,
or
fetal
crown
rump
distances.
No
treatment
related
visceral
or
skeletal
malformations/
variations
were
observed
in
any
of
the
fetuses.
Abortion
by
one
mid
dose
doe
was
assumed
to
be
due
to
excessive
maternal
toxicity
and
not
to
a
direct
effect
on
the
embryos
or
fetuses.
Therefore,
the
developmental
toxicity
NOAELis
>15
mg/
kg/
day
and
the
developmental
toxicity
LOAEL
was
not
identified.
This
study
is
classified
as
Unacceptable/
not
upgradable
and
does
not
satisfy
the
requirements
for
a
developmental
toxicity
study
(83
3b)
in
rabbits.
Several
deficiencies
were
noted
in
the
conduct
of
this
study:
the
subcutaneous
route
is
not
the
preferred
method
of
administration,
excessive
toxicity
occurred
at
the
high
dose,
percent
purity
of
the
test
article
wast
not
given,
dosing
solutions
were
not
analyzed
for
concentration,
stability,
or
homogeneity,
and
much
of
the
individual
maternal
and
fetal
data
were
not
included.
However,
these
study
results
may
be
used
in
conjunction
with
the
oral
developmental
toxicitystudyin
rabbits
(MRID42808002)
as
supplemental
information.
870.6300
Developmental
Neurotoxicity
Study
Rat
See
Section
4.
8
Neurotoxicity
for
Executive
Summary
4.4
Reproductive
Toxicity
Lindane/
September
2000
RED
Toxicology
Chapter
14
Adequacy
of
data
base
for
Reproductive
Toxicity:
The
data
base
for
reproductive
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
Both
parental
and
offspring
LOAELs
are
13
mg/
kg;
however
there
is
a
qualitative
difference
in
the
severity
of
effects.
In
the
parental
animals,
toxicity
was
seen
in
the
form
of
reduction
in
body
weight
gain
during
gestation
while
offspring
toxicity
was
correlated
with
decreases
in
pup
viability
and
pup
body
weight
in
the
F1
and
F2
generations
as
well
as
delayed
maturation
in
the
F2
generation.
Evidence
for
quantitative
increase
in
susceptibility
could
not
be
ascertained
due
to
the
wide
spread
in
the
doses
tested.
870.3800
Reproduction
and
Fertility
Effects
Rat
EXECUTIVE
SUMMARY:
In
a
multigeneration
reproductive
toxicity
study
(MRID
42246101),
lindane
(99.5%
a.
i.;
Batch
No.
DA433)
was
administered
to
groups
of
30
male
and
30
female
Charles
River
CD
rats
at
dietary
concentrations
of
0,
1,
20,
or
150
ppm
(0.
087,
1.71,
and
13.05
mg/
kg/
day,
respectively)
during
the
per
mating
period
for
two
generations.
One
litter
was
produced
in
each
generation.
F1
pups
chosen
as
parental
animals
were
weaned
onto
the
same
diet
as
their
parents.
Test
or
control
diets
were
administered
to
the
F0
and
F1
parental
animals
for
71
and
70
days,
respectively,
before
the
animals
were
mated
within
the
same
dose
group.
All
animals
were
continuously
exposed
to
test
material
either
in
the
diet
or
during
lactation
until
sacrifice.
Premature
sacrifices
or
intercurrent
deaths
of
two
F0
animals
and
five
F1
animals
were
considered
incidental
to
treatment;
all
other
F0
and
F1
males
and
females
survived
to
terminal
sacrifice.
No
treatment
related
clinical
signs
of
toxicity
were
observed
in
males
or
females
of
either
generation
at
any
time
during
the
study.
No
treatment
related
effects
on
body
weights,
body
weight
gains,
food
consumption,
or
food
efficiency
were
observed
for
the
F0
and
F1
males
and
females
during
premating.
Gross
necropsy
and
histopathology
of
females
was
unremarkable.
During
gestation
days
10
13,
mean
body
weight
gain
by
the
high
dose
F0
females
was
significantly
reduced
(11%).
Mean
body
weight
gains
by
the
high
dose
F0
females
were
also
significantly
lower
on
lactation
day
1
(interval
not
specified)
as
compared
to
the
controls,
but
recovery
was
apparent
by
weaning.
No
treatment
related
changes
in
body
weights
or
body
weight
gains
were
observed
in
the
F1
females
during
gestation
or
lactation.
High
dose
male
rats
of
both
generations
had
a
significantly
(p
0.01)
increased
incidence
of
pale
kidneys
(10/
29
F0
males
and
10/
30
F1
males)
as
compared
with
the
controls
(0/
30
and
0/
28,
respectively).
Areas
of
change
on
the
kidneys
(not
defined)
were
observed
in
7/
29
high
dose
F0
males
compared
with
2/
30
controls
and
in
4/
30
mid
dose
F1
males
and
5/
30
high
dose
F1
males
compared
with
1/
28
controls.
Significantly
(p
<
0.01)
increased
incidence
of
hydronephrosis
was
observed
in
high
dose
F1
males
(7/
30)
as
compared
to
controls
(0/
28).
Absolute
and
relative
kidney
weights
of
the
mid
and
high
dose
F0
males
and
the
high
dose
F1
males
were
significantly
(p
0.01)
increased
as
compared
with
the
controls.
F0
and
F1
males
in
the
mid
and
high
dose
groups
had
significantly
(p
0.01)
increased
incidences
of
chronic
interstitial
nephritis,
cortical
tubular
cell
regeneration,
hyaline
droplets
in
proximal
tubules,
tubular
necrosis
with
exfoliation
and
cellular
casts,
and
cortical
tubular
casts
(n.
s.).
These
changes
are
characteristic
of
alpha
2
globulin
accumulation,
which
is
specific
to
male
rats.
Lindane/
September
2000
RED
Toxicology
Chapter
15
Increased
absolute
and
relative
liver
weights,
accompanied
by
hepatocellular
hypertrophy,
in
the
mid
and
high
dose
males
and
females
of
both
generations
were
considered
adaptive
and
of
no
biological
significance.
Therefore,
the
LOAEL
for
systemic
toxicity
is
150
ppm
(13.05
mg/
kg/
day)
based
on
decreased
body
weight
gains
by
the
F0
females
during
gestation.
The
systemic
toxicity
NOAEL
is
20
ppm.
In
addition,
the
LOAEL
for
male
rats
is
20
ppm
(1.
71
mg/
kg/
day)
based
on
increased
kidney
weights
and
histopathological
lesions
in
the
kidney
characteristic
of
alpha
2µ
globulin
accumulation;
the
NOAEL
for
males
is
1
ppm
(0.
087
mg/
kg/
day).
Mating,
fertility,
gestation
survival
(postimplantation
index),
and
liveborn
indices,
mean
precoital
interval,
and
mean
gestation
length
were
similar
between
the
treated
and
control
groups
of
both
generations.
The
sex
distribution
was
not
affected
by
the
test
material.
Mean
litter
sizes
of
the
treated
groups
were
not
different
from
the
controls
throughout
lactation
for
both
generations.
Viability
indices
for
the
high
dose
F1
and
F2
pups
were
81%
and
85%,
respectively,
compared
with
96%
for
the
controls.
This
reduction
in
survival
on
lactation
day
4
was
due
to
the
death
or
sacrifice
(for
humane
reasons)
of
three
F1
litters
and
two
F2
litters.
No
treatment
related
clinical
signs
of
toxicity
were
observed
in
the
pups
of
either
generation
during
lactation.
Pup
necropsy
was
unremarkable.
Body
weights
of
the
low
and
mid
dose
F1
and
F2
pups
were
similar
to
the
controls
throughout
lactation.
Body
weights
of
the
high
dose
pups
of
both
generations
were
significantly
(p
0.01)
less
than
the
controls
on
lactation
days
1
and
25.
In
high
dose
F2
pups,
the
onset
and
completion
of
tooth
eruption
and
completion
of
hair
growth
were
significantly
(p
0.01)
delayed
10.5%,
11.6%,
and
24%,
respectively,
as
compared
with
the
controls.
Therefore,
the
LOAEL
for
reproductive
toxicity
is
150
ppm
(13.05
mg/
kg/
day)
based
on
reduced
pup
body
weights
and
decreased
viability
in
both
generations
and
delayed
maturation
of
the
F2
pups.
The
reproductive
toxicity
NOAEL
is
20
ppm
(1.71
mg/
kg/
day).
This
study
is
classified
as
Acceptable/
guideline
and
satisfies
the
guideline
requirements
for
a
reproduction
study
(83
4)
in
rats.
No
major
deficiencies
were
identified
in
the
conduct
of
this
study.
4.5
Chronic/
Carcinogenicity
Toxicity
Adequacy
of
data
base
for
chronic
toxicity:
The
data
base
for
chronic
toxicity
is
considered
complete.
No
additional
studies
are
required
at
this
time.
The
liver
appears
to
be
the
major
target
organ.
The
incidence
of
periacinar
hepatocytic
hypertrophy
was
significantly
(p
0.01)
increased
in
the
100
and
400
ppm
(4.
81
and
6.00
mg/
kg/
day,
respectively)
males
and
the
400
ppm
females
at
30
days
and
26
weeks.
In
addition,
increased
liver
and
spleen
weights,
and
decreased
platelets
were
also
noted.
Kidney
lesions
in
males
indicative
of
alpha
2µ
globulin
accumulation
were
observed
in
animals
treated
with
10
ppm,
but
are
not
considered
relevant
to
human
health
risk
assessment.
Lindane/
September
2000
RED
Toxicology
Chapter
16
870.4100a
(870.4300)
Chronic
Toxicity
B
Rat
EXECUTIVE
SUMMARY:
Results
from
interim
sacrifice
of
15
rats/
sex/
group,
at
30
days
and
26
weeks,
of
an
ongoing
chronic/
oncogenicity
study
are
presented
in
this
report
(MRID
41094101).
In
the
chronic
toxicity/
oncogenicity
study
(MRID41853701),
lindane
(99.75%
a.
i.,
Lot
no.
DA433)
was
administered
in
the
diet
to
groups
of
115
male
and
115
female
Wistar
rats
at
concentrations
of
0,
1,
10,
100,
or
400
ppmfor
2
years.
Corresponding
delivered
doses
were
0,
0.
05,
0.47,
4.81,
and
19.66
mg/
kg/
day,
respectively,
for
males
and
0,
0.
06,
0.59,
6.00,
and
24.34
mg/
kg/
day,
respectively,
for
females.
No
clinical
signs
of
toxicity
were
observed.
Mortalities
in
the
0,
1,
10,
100,
and
400
ppm
groups
included
1,
2,
2,
2,
and
0
males,
respectively,
and
2,
0,
1,
1,
and
8
females,
respectively.
Deaths
in
high
dose
females
occurred
during
weeks
2
4
and
the
cause
of
death
was
not
determined.
Body
weights
were
slightly
less
than
the
controls
for
the
high
dose
males
(
6%)
and
females
(
8%)
during
weeks
1
5
of
the
study,
but
gradually
increased
to
within
2%
of
the
control
level
by
week
26
for
males
and
week
9
10
for
females.
Food
consumption
was
"marginally
lower"
in
high
dose
males
and
females
and
water
consumption
was
"marginallyhigher"
in
high
dose
males
(63
ml/
kg/
day
versus
50
ml/
kg/
day
for
controls).
High
dose
females
had
significantly
(p
0.01)
decreased
hemoglobin
(
4
to
7%)
at
weeks
3,
12,
and
24,
decreased
RBC
counts
(
6
to
6.
3%)
at
weeks
3
and
24,
and
decreased
PCV
(
4.
2
to
9.
1%)
at
weeks
3
and
24.
These
red
cell
parameters
were
"marginally
lower"
for
high
dose
males,
but
statistical
significance
was
not
reached.
Platelet
counts
were
increased
by
up
to
13
14%
in
mid
not
defined)
and
high
dose
males
(week
12)
and
females
(week
24).
White
cell
counts
were
significantly
(p
0.05)
increased
27.5%
in
mid
dose
(not
defined)
and
23.5%
in
high
dose
females
due
to
increases
in
neutrophils.
Statistically
significant
(p
0.05
or
0.01)
changes
in
clinical
chemistry
parameters
were
observed
in
high
dose
males
and
females
during
the
first
24
weeks.
Inorganic
phosphorous
was
increased
by
7.3
29%
and
calcium
was
increased
by
3.5
10%.
Females
in
the
1,
10,
and
100
ppm
groups
also
had
significantly
(+
6
to
+8%;
p
0.01)
increased
calcium
levels
at
week
3
as
compared
with
the
controls.
Differences
in
urea
and
total
cholesterol
by
the
high
dose
males
and
females
were
not
consistent
over
time
and
did
not
appear
to
be
dose
related.
Urinalyses
were
conducted
by
routine
analysis,
after
water
deprivation,
and
after
water
loading.
Differences
in
urinalysis
parameters
between
treated
and
control
females
were
considered
random
and
not
treatment
related.
No
clear
evidence
of
an
effect
on
kidney
function
was
observed
in
males.
Absolute
kidney
weights
were
significantly
(p
0.05
or
0.01)
increased
in
high
dose
males
by
12.9%
and
39.3%,
and
relative
kidney
weights
were
increased
by
27.3%
and
43.0%
at
30
days
and
26
weeks,
respectively.
Absolute
and
relative
kidney
weights
from
the
100
ppm
males
were
increased
by
16.
9%
and
23.
6%,
respectively,
at
30
days,
but
were
similar
to
the
controls
at
26
weeks.
Absolute
liver
weights
were
significantly
(p
0.01)
increased
by
40.8%
in
high
dose
males
at
26
weeks
and
by
29.3%
and
32.3%
in
high
dose
females
at
30
days
and
26
weeks,
respectively.
Lindane/
September
2000
RED
Toxicology
Chapter
17
Relative
liver
weights
of
the
high
dose
males
and
females
were
significantly
(p
0.05
or
0.01)
were
greater
(14.0
37.2%)
than
the
controls
at
both
sacrifice
times.
Increases
in
the
incidence
of
pale
kidneys
in
100
and
400
ppmmales
were
noted
at
necropsy.
At
both
30
days
and
26
weeks
hyaline
droplets
in
the
proximal
tubules
were
observed
in
the
kidneys
of
all
males
(10/
10;
p
0.01)
receiving
10,
100,
and
400
ppm
compared
with
none
of
the
controls.
Tubular
regeneration
(p
0.01)
was
observed
after
30
days
in
9
10/
10
males
treated
with
10
ppm,
but
at
26
weeks
was
seen
in
only
8/
10
males
given
100
ppm
and
7/
10
given
400
ppm.
In
the
100
and
400
ppm
groups,
interstitial
chronic
nephritis
occurred
in
5
6
males
at
30
days
and
26
weeks
and
cortical
tubular
necrosis
was
observed
in
9
10
males
at
30
days.
At
26
weeks
cortical
tubular
necrosis
was
seen
in
only
2
100
ppmmales
and
5
(p
0.05)
400
ppmmales.
These
treatment
related
kidney
lesions
were
not
observed
in
control
males
or
in
females
at
any
dose
level.
The
incidence
of
periacinar
hepatocytic
hypertrophy
was
significantly
(p
0.01)
increased
in
the
100
and
400
ppm
males
and
the
400
ppm
females
at
30
days
and
26
weeks.
At
30
days
the
incidences
were
7/
10
and
10/
10
for
males,
respectively,
and
9/
9
for
females.
After
26
weeks
of
treatment,
the
incidences
were
8/
10
and
10/
10
for
males,
respectively,
and
9/
9
for
females.
This
lesion
was
not
seen
in
control
animals
of
either
sex.
No
treatment
related
histopathological
lesions
were
observed
in
the
spleen,
adrenals,
brain,
or
thymus.
Bone
marrow
data
presentation
was
inadequate
for
assessment.
Therefore,
the
systemic
toxicity
LOAEL
is
10
ppm
(0.
59
mg/
kg/
day)
based
on
microscopic
lesions
in
the
kidney
of
male
rats.
The
systemic
toxicity
NOAEL
is
1
ppm
(0.06
mg/
kg/
day).
This
study
is
considered
Acceptable/
nonguideline
as
an
interim
report
for
a
combined
chronic
toxicity/
oncogenicity
study
in
rats
[83
5].
It
is
sufficient
for
the
purpose
for
which
it
was
intended
as
an
interim
report.
EXECUTIVE
SUMMARY:
In
a
chronic
toxicity/
oncogenicity
study
(MRID
41853701),
lindane
(99.
75%
a.
i.,
Lot
no.
DA433)
was
administered
in
the
diet
to
groups
of
50
male
and
50
female
Wistar
rats
at
concentrations
of
0,
1,
10,
100,
or
400
ppm
for
2
years.
Corresponding
delivered
doses
were
0,
0.
05,
0.47,
4.81,
and
19.66
mg/
kg/
day,
respectively,
for
males
and
0,
0.
06,
0.59,
6.00,
and
24.34
mg/
kg/
day,
respectively,
for
females.
An
additional
15
rats/
sex/
group
were
designated
for
interimsacrifices
at
30
days
and
26
weeks
(the
results
fromthese
interimsacrifices
are
presented
separately
(MRID
41094101);
more
sacrifices
were
performed
at
52
and
78
weeks.
Clinical
signs
of
toxicity
consisted
of
convulsions
in
11
high
dose
females.
No
other
clinical
signs
were
observed.
Survival
at
the
end
of
the
study
was
36,
36,
31,
20,
and
16%
for
males
and
49,
38,
44,
35,
and
18%
for
females
in
the
0,
1,
10,
100,
and
400
ppm
groups,
respectively.
Survival
of
high
dose
males
was
similar
to
the
controls
through
week
93.
For
females,
however,
survival
was
significantly
decreased
in
the
high
dose
group
with
50%
survival
reached
at
week
89
compared
to
week
104
for
the
control
group.
Body
weight
gains
were
significantly
(p
0.01)
decreased
for
the
100
and
400
ppm
males
during
the
first
few
weeks
of
the
study
as
compared
to
the
controls.
Because
final
body
weights
of
Lindane/
September
2000
RED
Toxicology
Chapter
18
t
he
100
ppm
males
were
similar
to
the
controls,
the
initial
reduction
in
weight
gain
was
not
considered
biologically
significant.
Final
body
weights
of
the
high
dose
males
were
significantly
14
p
0.
05)
less
than
the
controls.
Body
weights
and
body
weight
gains
for
the
treated
females
were
similar
to
the
controls
throughout
the
study.
Food
consumption
by
the
high
dose
groups
was
decreased
15%
in
males
and
19%
in
females
during
the
first
week
of
the
study,
however,
total
food
consumption
for
the
entire
study
was
similar
to
the
control
levels.
Platelet
counts
were
significantly
(p
0.05
or
0.01)
increased
(20%
or
less
)
in
the
100
and
400
ppm
males
at
week
12
and
in
100
and
400
ppm
males
and
females
at
week
24,
but
not
at
later
time
points.
High
dose
males
and
females
had
significant
(p
0.05
or
0.01)
decreases
in
red
blood
cell
parameters
at
week
104
as
compared
with
the
controls:
hemoglobin
was
15.6%
and
17.6%,
respectively,
erythrocyte
counts
were
14.1%
and
21%,
respectively,
and
PCV
was
15.9%
and
18.2
respectively.
Significant
(p
0.05
or
0.01)
changes
in
clinical
chemistry
parameters
were
observed
in
highdose
males
and
females
during
the
first
year
of
the
study.
Inorganic
phosphorous
was
increased
by
7.3
38.5%
and
calcium
was
increased
by
3.4
10%
in
males
and
females;
cholesterol
was
increased
by
45
110%
and
urea
was
increased
by
20
54%
in
females;
and
the
albumin/
globulin
ratio
was
decreased
by
8.
3
18.
2%
in
females.
All
parameters
were
similar
to
the
control
levels
by
week
104.
High
dose
males
and
females
had
increased
absolute
and
relative
liver
weights
at
all
interim
sacrifices,
although
statistical
significance
was
not
always
reached.
At
study
termination,
absolute
and
relative
liver
weights
were
significantly
(p
0.01)
increased
by
21.2%
and
38.5%,
respectively,
in
high
dose
males
and
by
31.6%
and
33.5%,
respectively,
in
high
dose
females.
At
100
ppm,
absolute
liver
weights
were
increased
by
8.6
11.2%
(n.
s.)
and
relative
liver
weights
were
increased
by
14.4
17.6%
(p
0.05
or
0.01)
for
both
sexes
at
week
104.
Significant
(p
0.05
or
0.01)
increases
in
absolute
and
relative
spleen
weights
at
week
52
and
in
relative
spleen
weights
at
week
104
were
also
noted,
but
the
sex
was
not
identified.
The
incidence
rate
of
periacinar
hepatocytic
hypertrophy
was
significantly
increased
in
the
100
and
400
ppmgroups
with
25/
50
males
and
19/
50
females
affected
at
100
ppm
and
40/
50
males
and
43/
50
females
affected
at
400
ppm.
No
treatmentrelated
histopathological
lesions
were
observed
in
the
spleen
or
bone
marrow.
Kidney
lesions
in
males
indicative
of
alpha
2µ
globulinaccumulation
were
observed
in
animals
treated
with
10
ppm,
but
are
not
considered
relevant
to
human
health
risk
assessment.
Therefore,
the
systemic
toxicity
LOAEL
for
male
and
female
rats
is
100
ppm
(4.
81
and
6.00
mg/
kg/
day,
respectively)
based
on
periacinar
hepatocyte
hypertrophy,
increased
liver
and
spleen
weights,
and
decreased
platelets.
The
systemic
toxicity
NOAEL
is
10
ppm.
Among
high
dose
males,
there
was
an
apparent
increase
in
adrenal
pheochromocytomas.
The
percentage
of
animals
with
tumors
(benign
and
malignant)
was
14,
12,
19,
14,
and
26%
in
the
0,
1,
10,
100,
and
400
ppm
groups,
respectively.
Statistical
significance
can
be
shown
depending
on
the
test
used.
Based
on
the
data
presented
in
this
study,
an
assessment
of
the
carcinogenic
potential
of
lindane
cannot
be
made.
Additional
histopathological
examination
of
the
adrenals
from
animals
in
Lindane/
September
2000
RED
Toxicology
Chapter
19
the
1,
10,
and
100
ppm
groups,
as
well
as
historical
control
data
for
this
tumor
type,
are
required.
These
data
were
submitted
as
a
separate
study
(MRID
42891401).
This
chronic
toxicity/
oncogenicity
study
in
the
rat
is
Unacceptable/
upgradable
and
does
not
satisfy
the
guideline
requirement
for
a
combined
chronic
toxicity/
oncogenicity
study
in
rats
[83
5].
Additional
data
on
adrenal
pheochromocytomas
is
necessary
to
complete
the
assessment.
EXECUTIVE
SUMMARY:
The
current
study
(MRID
42891201)
was
submitted
as
supplemental
information
to
the
combined
chronic
toxicity/
oncogenicity
study.
Data
fromadditional
microscopic
examination
of
the
adrenal
gland
from
males
in
the
low
and
two
mid
dose
groups
and
historical
control
data
are
included.
In
a
chronic
toxicity/
oncogenicity
study
(MRID
41853701),
lindane
(99.75%
a.
i.,
Lot
no.
DA433)
was
administered
in
the
diet
to
groups
of
50
male
and
50
female
Wistar
rats
at
concentrations
of
0,
1,
10,
100,
or
400
ppm
for
2
years.
Corresponding
delivered
doses
were
0,
0.
05,
0.47,
4.81,
and
19.66
mg/
kg/
day,
respectively,
for
males
and
0,
0.
06,
0.59,
6.00,
and
24.34
mg/
kg/
day,
respectively,
for
females.
An
additional
15
rats/
sex/
group
were
designated
for
interimsacrifices
at
30
days
and
26
weeks;
the
results
fromthese
interimsacrifices
are
presented
separately
(MRID
41094101).
Clinical
signs
of
toxicity
consisted
of
convulsions
in
11
high
dose
females.
No
other
clinical
signs
were
observed.
Survival
at
the
end
of
the
study
was
36,
36,
31,
20,
and
16%
for
males
and
49,
38,
44,
35,
and
18%
for
females
in
the
0,
1,
10,
100,
and
400
ppm
groups,
respectively.
Survival
of
high
dose
males
was
similar
to
the
controls
through
week
93.
For
females,
however,
survival
was
significantly
decreased
in
the
high
dose
group
with
50%
survival
reached
at
week
89
compared
to
week
104
for
the
control
group.
Body
weight
gains
were
significantly
(p
0.01)
decreased
for
the
100
and
400
ppm
males
during
the
first
few
weeks
of
the
study
as
compared
to
the
controls.
Because
final
body
weights
of
the
100
ppm
males
were
similar
to
the
controls,
the
initial
reduction
in
weight
gain
was
not
considered
biologically
significant.
Final
body
weights
of
the
high
dose
males
were
significantly
14
p
0.
05)
less
than
the
controls.
Body
weights
and
body
weight
gains
for
the
treated
females
were
similar
to
the
controls
throughout
the
study.
Food
consumption
by
the
high
dose
groups
was
decreased
15%
in
males
and
19%
in
females
during
the
first
week
of
the
study,
however,
total
food
consumption
for
the
entire
study
was
similar
to
the
control
levels.
Platelet
counts
were
significantly
(p
0.05
or
0.01)
increased
(20%
or
less)
in
the
100
and
400
ppm
males
at
week
12
and
in
100
and
400
ppm
males
and
females
at
week
24,
but
not
at
later
time
points.
High
dose
males
and
females
had
significant
(p
0.05
or
0.01)
decreases
in
red
blood
cell
parameters
at
week
104
as
compared
with
the
controls:
hemoglobin
was
15.6%
and
17.6%,
respectively,
erythrocyte
counts
were
14.1%
and
21%,
respectively,
and
PCV
was
15.9%
and
18.2
respectively.
Significant
(p
0.05
or
0.01)
changes
in
clinical
chemistry
parameters
were
observed
in
highdose
males
and
females
during
the
first
year
of
the
study.
Inorganic
phosphorous
was
increased
by
Lindane/
September
2000
RED
Toxicology
Chapter
20
7.3
38.5%
and
calcium
was
increased
by
3.4
10%
in
males
and
females;
cholesterol
was
increased
by
45
110%
and
urea
was
increased
by
20
54%
in
females;
and
the
albumin/
globulin
ratio
was
decreased
by
8.
3
18.
2%
in
females.
All
parameters
were
similar
to
the
control
levels
by
week
104.
High
dose
males
and
females
had
increased
absolute
and
relative
liver
weights
at
all
interim
sacrifices,
although
statistical
significance
was
not
always
reached.
At
study
termination,
absolute
and
relative
liver
weights
were
significantly
(p
0.01)
increased
by
21.2%
and
38.5%,
respectively,
in
high
dose
males
and
by
31.6%
and
33.5%,
respectively,
in
high
dose
females.
At
100
ppm,
absolute
liver
weights
were
increased
by
8.6
11.2%
(n.
s.)
and
relative
liver
weights
were
increased
by
14.4
17.6%
(p
0.05
or
0.01)
for
both
sexes
at
week
104.
Significant
(p
0.05
or
0.
01)
increases
in
absolute
and
relative
spleen
weights
at
week
52
and
in
relative
spleen
weights
at
week
104
were
also
noted,
but
the
sex
was
not
identified.
The
incidence
rate
of
periacinar
hepatocytic
hypertrophy
was
significantly
increased
in
the
100
and
400
ppm
groups
with
25/
50
males
and
19/
50
females
affected
at
100
ppm
and
40/
50
males
and
43/
50
females
affected
at
400
ppm.
No
treatment
related
histopathological
lesions
were
observed
in
the
spleen
or
bone
marrow.
Kidneylesions
in
males
indicative
of
alpha
2µ
globulin
accumulation
were
observed
in
animals
treated
with
10
ppm,
but
are
not
considered
relevant
to
human
health
risk
assessment.
Therefore,
the
systemic
toxicity
LOAEL
for
male
and
female
rats
is
100
ppm
(4.
81
and
6.00
mg/
kg/
day,
respectively)
based
on
periacinar
hepatocyte
hypertrophy,
increased
liver
and
spleen
weights,
and
decreased
platelets.
The
systemic
toxicity
NOAEL
is
10
ppm
(0.
47
and
0.59
mg/
kg/
day,
males
and
females,
respectively).
Eight
additional
males
were
identified
as
having
adrenal
pheochromocytomas.
The
revised
percentages
of
animals
with
adrenal
tumors
in
the
0,
1,
10,
100,
and
400
ppm
groups
are
14,
16,
16,
6,
and
24%
for
benign
tumors,
respectively,
and
0,
0,
6,
8,
and
2%
for
malignant
tumors,
respectively.
Statistical
significance
was
not
reached
by
relevant
tests.
For
comparison,
historical
control
data
fromCharles
River
and
publications
in
the
open
literature
were
submitted.
The
10
and
100
ppm
groups
had
malignant
tumor
incidence
rates
greater
than
the
historical
control
rate
(0
2%).
The
high
dose
group
also
had
a
slight
excess
of
benign
and
combined
tumor
rates
as
compared
with
the
historical
control
rates
(8
22%
benign,
combined
could
not
be
calculated),
but
this
same
net
tumor
incidence
was
the
same
as
the
control
group
of
a
published
study.
In
the
current
study,
pheochromocytomas
were
not
considered
the
cause
of
death
for
any
animal
with
the
exception
of
a
single
animal
in
the
100
ppm
group.
Therefore,
no
evidence
dose
related
and
statisticallysignificant
increase
inadrenal
tumors
was
observed
in
this
study.
The
study
was
conducted
at
adequate
dose
levels.
This
chronic
toxicity/
oncogenicity
st
udy
in
the
rat
is
Acceptable/
guideline
(revised)
and
satisfies
the
guideline
requirement
for
a
combined
chronic
toxicity/
oncogenicity
study
in
rats
[83
5].
Lindane/
September
2000
RED
Toxicology
Chapter
21
870.4100b
Chronic
Toxicity
Dog
Chronic
studies
in
two
species,
rat
and
rabbit,
are
available.
See
chronic
oral
section
for
executive
summaries.
4.6
Carcinogenicity
Adequacy
of
data
base
for
Carcinogenicity:
The
data
base
for
carcinogenicity
is
considered
incomplete.
According
to
the
TES
committee
report
(1994),
lindane
has
not
been
classified
by
the
HED
Cancer
Peer
Review
Committee.
It
was
determined
by
the
RfD/
Peer
Review
Committee
(1993)
that:
"The
mouse
carcinogenicity
data
were
considered
insufficient
because
of
major
deficiencies
associated
with
all
studies
available."
Lindane
however
had
been
previously
(1985)
classified
by
the
Cancer
Assessment
Group
of
the
Office
of
Research
and
Development
as
a
group
B2/
C
carcinogen
based
on
increased
incidence
of
mouse
liver
tumors.
The
upper
bound
slope
of
the
dose
response
was
given
in
that
memorandumas
Q1*
=
1.1
(mg/
kg/
day)
1
.
Amouse
carcinogenicity
study
is
expected
to
be
submitted
in
December
2000.
870.4200a
Carcinogenicity
Study
rat
See
the
chronic
toxicity
section
for
executive
summaries
870.4200b
Carcinogenicity
(feeding)
Mouse
A
new
study
is
expected
in
December
2000.
EXECUTIVE
SUMMARY:
In
a
special
study,
(MRID
none)
three
strains
of
female
mice,
agouti,
pseudoagouti,
and
black,
were
administered
lindane
at
dietary
concentrations
of
0
or
160
ppm.
The
doses
were
selected
based
on
a
preliminary
st
udy
where
no
deaths
occurred
after
one
month.
Groups
of
36
96
animals
per
strain
were
continuously
fed
treated
or
control
diets
for
up
to
24
months.
Additional
groups
of
48
96
agouti
and
black
mice
were
fed
treated
or
control
diets
for
6
months
then
fed
control
diet
for
6
or
18
months
(recovery).
No
clinical
signs
of
toxicity
and
no
survival
information
were
reported.
No
apparent
effects
on
body
weights
or
food
consumption
were
observed,
but
only
limited
data
were
presented.
When
compared
with
untreated
controls
at
6
and
12
months,
benzo(
a)
pyrene
monooxygenase
activity
in
the
liver
was
increased
1.61
1.84x
in
the
agouti,
2.71
2.78x
in
the
pseudoagouti,
and
2.07
2.09x
in
the
black
strains.
Liver
weights
were
increased
14.7
31.2%
in
the
agouti,
13.5
22.0%
in
the
pseudoagouti,
and
12.2
16.4%
in
the
black
strains
at
interval
sacrifices
up
to
24
months.
Following
the
recovery
period,
liver
weights
of
the
treated
mice
were
similar
to
the
controls.
No
evidence
for
increased
incidence
or
decreased
latency
of
liver
tumors
was
observed
for
the
black
strain
at
any
time
during
the
study
(24
months)
or
for
the
pseudoagouti
strain
through
the
18
month
sacrifice.
At
18
months,
0/
34
control
and
12/
36
(33%)
of
the
treated
agouti
mice
Lindane/
September
2000
RED
Toxicology
Chapter
22
developed
hepatocellular
adenomas;
one
carcinoma
each
in
the
treated
and
control
groups
was
noted.
Both
the
treated
agouti
and
pseudoagouti
strains
had
clear
increases
in
adenomas
and
slight
increases
in
carcinomas
at
24
months.
The
incidence
rates
for
the
control
and
treated
agouti
groups
were
9%
and
35%,
respectively,
for
adenomas
and
13%
and
17%,
respectively,
for
carcinomas.
The
incidence
rates
for
the
control
and
treated
pseudoagouti
groups
were
5%
and
12%,
respectively,
for
adenomas
and
2%
and
5%,
respectively,
for
carcinomas.
Increases
in
Clara
cell
hyperplasia
were
noted
in
the
lung
at
all
sacrifice
intervals
for
each
strain
and
the
incidence
of
lung
tumors
was
increased
in
later
months
for
the
agouti
and
pseudoagouti
strains.
The
percentage
of
mice
with
Clara
cell
hyperplasia
in
the
control
and
treated
groups
was
631
and
72
92%,
respectively,
for
the
agouti;
6
17%
and
50
79%,
respectively,
for
the
pseudoagouti;
and
0
14%
and
56
90%,
respectively,
for
the
black.
Lung
tumors
for
the
agouti
strain
occurred
in
0%
of
the
control
and
17%
of
the
treated
animals
at
18
months
and
4%
of
the
control
and
19%
of
the
treated
animals
at
24
months.
Lung
tumors
in
the
pseudoagouti
strain
occurred
in
6%
of
the
controls
and
14%
of
the
treated
animals
at
24
months.
After
recovery,
the
incidences
of
Clara
cell
hyperplasia
(agouti
and
black)
and
lung
tumors
(agouti)
remained
slightly
elevat
ed
as
compared
with
the
controls.
In
conclusion,
dietary
administration
of
lindane
resulted
in
the
induction
of
liver
and
lung
tumors
in
the
agouti
and
pseudoagouti
mouse
strains
and
caused
increased
liver
weights,
increased
enzyme
activity,
and
irreversible
Clara
cell
hyperplasia
in
the
lung
of
all
three
mouse
strains
tested.
This
study
is
considered
Acceptable/
nonguideline
as
a
special
study
in
mice.
The
study
deficiencies
include:
only
females
tested,
only
one
dose
level
tested,
histopathology
data
provided
for
lung
and
liver
only,
lack
of
analytical
chemistry
data,
and
no
individual
animal
data.
These
study
results
can
be
used
as
supplementary
information
to
the
chronic/
oncogenicity
study
in
rats.
4.7
Mutagenicity
Adequacy
of
data
base
for
Mutagenicity:
The
data
base
for
Mutagenicity
is
considered
adequate
based
on
submitted
studies
and
reports
in
the
open
literature.
Lindane
does
not
appear
to
be
mutagenic.
In
a
mammalian
cell
gene
mutation
assay
and
an
in
vivo
sister
chromatid
exchange
assay,
no
mutagenic
response
was
detected.
The
open
literature
suggests,
however,
that
technical
grade
HCH
(hexachlorohexane;
6.
5%
HCH)
may
induce
some
mutagenic
activity
as
evidenced
in
a
dominant
lethal
mutation
assay
and
sister
chromatid
exchanges.
Overall,
based
on
the
results
of
acceptable
studies
on
lindane,
it
does
not
appear
to
have
mutagenic
potential.
Gene
Mutation
Lindane/
September
2000
RED
Toxicology
Chapter
23
cell
gene
mutation
assay
MRID
00144500
Unacceptable/
Guideline
In
a
mammalian
cell
gene
mutation
assay
conducted
in
Chinese
hamster
V79
cells,
lindane
was
tested
in
the
absence
of
metabolic
activation
at
dose
levels
of
2.5,
5,
10,
25,
50,
70,
100,
and
150
µg/
ml
and
in
the
presence
of
metabolic
activation
at
dose
levels
of
5,
10,
25,
50,
100
250
and
500
µg/
ml.
The
S9
fraction
used
for
metabolic
activation
was
obtained
from
Aroclor
1254
induced
mouse
liver.
Tests
with
and
without
activation
were
conducted
under
aerobic
and
anaerobic
conditions.
Under
anaerobic
conditions,
lindane
without
S9
was
cytotoxic
to
the
V79
cells
at
dose
levels
above
10
µg/
ml
and
with
S9
at
dose
levels
above
150
mg/
ml.
No
mutagenic
activity
of
lindane
was
observed
in
V79
cells
under
any
combination
of
conditions
up
to
cytotoxic
doses.
Cytogenetics
sister
chromatid
exchange
MRID
00024504
Acceptable/
Guideline
In
a
mammalian
in
vivo
sister
chromatid
exchange
(SCE)
assay,
50µg
tablets
of
bromodeoxy
uridine
were
implanted
into
male
and
female
CF
1
mice.
Two
hours
after
implantation,
lindane
was
administered
ip
in
arachis
oil
at
dose
levels
of
1.3,
6.4
and
32.1
mg/
kg.
For
each
dose
level
and
control
group,
30
bone
marrow
cells
from
each
of
5
animals
of
each
sex
were
examined
for
SCEs.
No
toxicity
was
reported
in
any
treatment
group.
When
results
for
male
and
female
animals
were
pooled,
only
the
highest
dose
produced
a
significant
increase
in
SCEs
over
the
controls.
Positive
control
values
were
appropriate.
,dominant
lethal
assay
MRID
00062657
Unacceptable/
Guideline
In
a
mammalian
dominant
lethal
assay,
10
male
Sprague
Dawley
rats
of
unspecified
age
per
group
were
exposed
to
lindane
administered
by
subcutaneous
injection
in
corn
oil
at
doses
of
0,
1,
3,
and
10
mg/
kg
five
time
per
week
for
10
weeks.
Uteri
were
examined
for
live
and
dead
implants
and
abnormalities.
Males
were
also
sacrificed
and
gross
pathological
analysis
performed.
The
incidence
of
dead
implants
was
significantly
increased
at
the
lowest
dose
but
not
at
the
two
higher
doses
in
the
first
week
of
mating
but
this
increase
was
not
observed
during
the
second
week.
The
authors
conclude
that
lindane
did
not
cause
an
increase
in
the
incidence
of
dominant
lethals
inthis
study.
4.8
Neurotoxicity
Adequacy
of
data
base
for
Neurotoxicity:
Neurotoxicity
studies
(acute,
subacute
and
developmental)
have
been
submitted.
Lindane
is
a
neurotoxicant.
In
acute,
subchronic
and
developmental
neurotoxicity
studies,
it
was
found
to
cause
neurotoxic
effects
including
tremors,
convulsions,
decreased
motor
activity,
increased
forelimb
grip
strength,
hypersensit
ivity
to
touch,
hunched
posture
and
decreased
motor
activity
habituation.
There
also
appears
to
be
a
greater
susceptibility
to
exposure
by
offspring
compared
to
parental
animals.
The
LOAEL
for
offspring
toxicity
is
50
ppm
(5.
6
mg/
kg/
day)
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation
compared
to
a
LOAEL
of
120
ppm
(13.7
mg/
kg/
day)
based
on
decreased
body
weight
gains,
Lindane/
September
2000
RED
Toxicology
Chapter
24
decreased
food
consumption,
and
increased
reactivity
to
handling
for
maternal
toxicity.
870.6100
Delayed
Neurotoxicity
Study
Hen
Not
required
870.6200
Acute
Neurotoxicity
Screening
Battery
EXECUTIVE
SUMMARY:
In
an
acute
oral
neurotoxicity
study
(MRID44769201),
groups
of
10
Crl:
CD®
BR
rats/
sex/
dose
were
administered
single
dose
of
lindane
(Batch
No.
HLS96/
1,
Purity
99.78%)
by
gavage
at
concentrations
of
0
(control),
6,
20,
or
60
mg/
kg.
Functional
observational
battery
(FOB)
and
motor
activity
(MA)
testing
were
performed
prior
to
administration
and
within
3
hours
(time
of
peak
effect)
of
dosing
(day
0),
and
on
days
7
and
14
post
dose.
Body
weights
were
recorded
pre
test,
weekly
during
the
study
period
and
on
FOB
assessment
days.
Clinical
signs
were
recorded
at
least
once
daily.
At
study
termination
all
animals
were
sacrificed
and
fixed
by
whole
body
perfusion,
designated
tissues
of
the
nervous
system
were
processed
for
microscopic
neuropathological
evaluation.
All
animals
survived
to
scheduled
termination.
One
male
in
the
60
mg/
kg
group
was
observed
to
convulse
on
the
day
of
treatment
within
2.
75
hours
after
dosing.
Clinical
signs
were
also
observed
in
females
treated
at
60
mg/
kg
within
24
hours
of
dosing
and
included:
staining
of
the
fur,
stained
urogenital
region,
hunched
posture,
and
piloerection.
These
effects
in
females
persisted
for
four
days.
Significant
treatment
related
decreases
in
body
weight
gains
were
observed
for
males
in
the
60
mg/
kg
group
compared
to
the
control
group
for
the
first
week
of
the
study.
Females
administered
this
concentration
also
had
slightly
lower
body
weight
gains
throughout
the
study.
Food
consumption
for
males
and
females
administered
60
mg/
kg
was
significantly
decreased
compared
to
controls
for
Week
1
of
the
study.
Food
conversion
ratios
in
the
treated
groups
were
not
changed
compared
to
control
groups.
At
the
first
FOB
assessment
on
Day
0
(3
hours
after
dosing)
males
and
females
in
the
60
mg/
kg
group
exhibited
piloerection
(1
,2
),
decreased
rectal
temperature
(1
,1
),
increased
hindlimb
foot
splay
and
hunched
posture
(4
,7
).
Among
males
dosed
at
60
mg/
kg,
increased
respiration
(3
,1
)
and
one
observation
of
tremor/
twitching
were
observed.
Females
administered
60
mg/
kg
were
observed
to
have
increased
incidences
of
walking
on
tip
toes
(10),
licking
behavior
(3),
decreased
foot
splay
(3)
and
an
absence
of
grooming
(8)
behavior.
Females
in
the
20
mg/
kg
also
had
decreased
grooming
(3)
behavior
and
increased
forelimb
grip
strength.
Motor
activity
was
significantly
decreased
for
males
and
females
treated
with
60
mg/
kg
as
well
as
among
females
treated
with
20
mg/
kg
three
hours
post
treatment.
The
6
mg/
kg
group
remained
comparable
to
controls
in
FOB
assessment
parameters
and
MA.
No
neuropathological
endpoints
were
observed
during
the
histological
examinations
of
the
peripheral
or
central
nervous
systems
of
these
animals
at
any
exposure
concentration.
The
NOAEL
for
systemic
toxicity
is
20
mg/
kg
for
males
and
6
mg/
kg
for
females.
Based
on
the
substance
related
effects
on
body
weight,
body
weight
gain,
food
consumption,
and
clinical
signs
of
toxicity
the
LOAEL
for
systemic
toxicity
in
males
is
60
mg/
kg.
The
LOAEL
for
females
is
20
mg/
kg
based
on
a
lower
incidence
of
grooming
behavior
and
decreased
Lindane/
September
2000
RED
Toxicology
Chapter
25
locomotor
activity
immediately
after
dosing,
in
addition
to
the
parameters
mentioned
above.
The
NOAEL
for
neurotoxic
effects
is
6
mg/
kg
for
females
and
the
LOAEL
is
20
mg/
kg
based
on
increased
forelimb
grip
strength
and
decreased
grooming
behavior
and
motor
activity
(MA).
The
NOAEL
for
neurotoxicity
in
males
is
20
mg/
kg
and
the
LOAEL
for
males
is
60
mg/
kg
based
on
tremors,
convulsions,
decreased
MA,
and
increased
forelimb
grip
strength.
This
study
is
classified
Acceptable/
guideline
and
satisfies
the
Subdivision
F
guideline
requirement
for
an
acute
oral
neurotoxicity
study
(§
81
8)
in
rats.
870.6200
Subchronic
Neurotoxicity
Screening
Battery
EXECUTIVE
SUMMARY:
In
a
subchronic
oral
neurotoxicity
study
(MRID
44781101),
groups
of
10
Crl:
CD®
BR
rats/
sex/
group
were
administered
lindane
(Batch
No.
HLS96/
1,
Purity
99.78%)
in
the
diet
for
13
weeks
at
concentrations
of
0
(control),
20,
100,
or
500
ppm.
Due
to
severe
toxic
reactions
to
treatment
at
500
ppm,
the
dose
was
reduced
to
400
ppm
on
day
11
of
treatment
thereafter.
These
doses
resulted
in
average
daily
intake
values
of
0,
1.4,
7.1,
and
28.1
mg/
kg/
day
for
males
and
0,
1.6,
7.9,
and
30.2
mg/
kg/
day
in
females
for
0,
20,
100,
and
500/
400
ppm,
respectively.
Functional
observational
battery
(FOB)
and
motor
activity
(MA)
tests
were
performed
prior
to
administration
and
after
4,
8,
and
13
weeks
of
treatment.
Body
weights
were
recorded
pretest
weekly
during
the
study
period
and
on
FOB
assessment
days.
Clinical
signs
were
recorded
at
least
once
daily.
At
study
termination
all
animals
were
sacrificed
and
fixed
by
whole
body
perfusion
and
designated
tissues
of
the
nervous
system
were
processed
for
microscopic
neuropathological
evaluation.
Three
females
in
the
500/
400
group
died
prior
to
scheduled
termination.
These
deaths
were
attributed
to
treatment
with
lindane.
One
death
was
recorded
on
Day
11
of
the
study,
one
during
week
10
and
one
during
week
13.
Clinical
signs
prior
to
death
included
weight
loss,
swollen
muzzle
with
scabbing,
hunched
posture,
piloerection,
and
staining
of
the
anogenital
region.
Observations
in
surviving
females
treated
at
500/
400
ppmwere
hypersensitivity
to
touch,
staining
of
the
urogenital
region,
and
scabbing
of
the
toes.
Significant
treatment
related
decreases
(p<
0.05
or
p<
0.01)
in
body
weight
were
observed
among
males
and
females
treated
with
500/
400
ppm
of
14%
and
23%,
respectively.
Decreases
in
body
weight
gains
(70%
and
180%
,
p<
0.01),
food
consumption
(35%
and
50%
,p<
0.
05or
p<
0.01,
respectively),
and
food
conversion
ratios
were
observed
for
males
and
females
in
the
500
ppm
groups
compared
to
the
control
group
for
the
first
week
of
the
study.
Male
rats
tended
to
recover
from
these
effects
after
the
dose
was
lowered.
Females,
however,
did
not
exhibit
this
same
level
of
recovery
as
their
food
consumption
remained
slightly
depressed
throughout
the
remainder
of
the
study.
Females
in
the
100
ppm
group
had
significantly
decreased
body
weight
gains
(40%,
p<
0.05)
compared
to
the
control
group
during
the
first
week
of
the
study
and
this
effect
continued,
although
not
at
a
level
of
significance
throughout
the
remainder
of
the
study.
Females
in
the
100
ppm
group
had
significantly
decreased
food
consumption
(16%,
p<
0.01)
for
the
first
week
of
the
study
and
this
Lindane/
September
2000
RED
Toxicology
Chapter
26
trend
continued
throughout
the
study.
Liver
weights
were
also
found
to
be
increased
at
500/
400
ppm
for
both
sexes;
no
additional
information
was
given.
During
the
FOB
assessment
(table
A
is
attached
at
t
he
end
of
this
document),
males
and
females
treated
at
the
highest
dose
(500/
400
ppm)
were
perceived
as
difficult
to
handle.
They
also
were
observed
to
have
piloerection
and
hunched
posture.
Females
in
the
highest
dose
group
had
missing
claws
(3),
tended
to
urinate
more
often
than
controls,
had
a
higher
incidence
of
grooming
behavior,
rearing,
motor
activity,
and
one
female
was
observed
to
convulse.
Females
across
the
dose
groups
were
observed
walking
on
tiptoes
(5
7)
and
these
incidences
were
significantly
increased
compared
to
the
control
(1)
for
the
highest
dose
group.
Females
(5)
in
the
100
ppm
group
also
had
increased
incidences
of
grooming
behavior
at
the
Week
4
evaluation
and
one
animal
in
this
group
was
extremely
difficult
to
handle.
The
assessments
of
forelimb
and
hindlimb
grip
strength
as
well
as
hindlimb
splay
revealed
no
differences
for
any
of
the
treated
groups
compared
to
the
control
groups.
Colburn
motor
activity
was
also
similar
among
treated
groups
compared
to
the
control
groups.
No
neuropathological
endpoints
attributable
to
lindane
administration
were
observed
during
the
histological
examinations
of
the
peripheral
or
central
nervous
systems
of
these
animals
at
any
exposure
concentration.
The
NOAEL
for
systemic
toxicity
is
100
ppm
for
males
(7.
1
mg/
kg)
and
20
ppm
for
females
(1.6
mg/
kg).
Based
on
the
substance
related
effects
on
body
weight,
body
weight
gain,
food
consumption,
and
clinical
signs
of
toxicity
the
LOAELlevels
for
systemic
toxicity
in
males
is
500/
400
ppm
(28.1
mg/
kg)
and
100
ppm
for
females
(7.
9
mg/
kg).
The
NOAEL
for
neurotoxic
effects
is
100
ppm
for
males
(7.
1
mg/
kg)
and
females
(7.
9
mg/
kg).
The
neurotoxicity
LOAEL
is
500/
400
ppm
based
on
hypersensitivity
to
touch
and
hunched
posture.
This
study
is
classified
Acceptable/
guideline
and
satisfies
the
Subdivision
F
guideline
requirement
for
an
acute
oral
neurotoxicity
study
(§
81
8)
in
rats.
870.6300
Developmental
Neurotoxicity
Study
EXECUTIVE
SUMMARY:
In
a
developmental
neurotoxicity
study
(MRID
45073501),
lindane
(Batch
No.
HLS
96/
1;
99.78%
a.
i.)
was
administered
to
presumed
pregnant
Hsd
Brl
Han:
Wist
(Han
Wistar)
rats
in
the
diet
at
concentrations
of
0,
10,
50,
or
120
ppm
fromgestation
day
(GD)
6
through
lactation
day
10.
These
concentrations
resulted
in
F0
maternal
doses
of
0.
8
0.
9,
4.
24.6
and
8.
0
10.5
mg/
kg/
day,
respectively,
during
gestation
and
1.
2
1.
7,
5.
6
8.
3,
and
13.7
19.1
mg/
kg/
day,
respectively,
during
lactation.
The
developmental
neurotoxicityof
lindane
was
evaluated
in
the
F1
offspring.
F1
animals
(10/
sex)
were
evaluated
for
FOB,
motor
activity,
auditory
startle
response,
and
learning
and
memory
as
well
as
developmental
landmarks
such
as
vaginal
perforation
and
balanopreputial
separation,
and
brain
weights
and
histopathology
on
days
11
and
65,
including
Lindane/
September
2000
RED
Toxicology
Chapter
27
morphometrics.
Small
differences
in
absolute
maternal
body
weights
(7
8%)
were
observed
between
the
high
dose
and
control
groups
during
gestation
and
early
lactation
(through
day
11).
Body
weight
gains
by
the
high
dose
dams
from
GD
6
through
GD
20
were
64
79%
(p
0.
01)
of
the
control
level.
Body
weight
changes
during
lactation
were
similar
between
the
treated
and
control
groups.
During
gestation,
food
consumption
by
the
high
dose
group
was
significantly(
p
0.01;
74
92%
of
controls)
less
than
the
control
group
for
the
intervals
of
GD
10
13,
14
17,
and
18
19.
Food
consumption
by
the
low
and
mid
dose
groups
during
gestation
and
by
all
treated
groups
during
lactation
was
similar
to
the
controls.
Absolute
body
weights
of
the
treated
male
and
female
pups
in
mid
and
high
dose
groups
during
lactation
were
12
18%
and
16
20%
less
than
controls,
respectively
on
days
4
11
of
lactation
with
recovery
to
less
than
10%
by
day
21.
Body
weight
gains
(p
0.05
or
0.01)
on
lactation
days
1
4
and
1
11
were
76%
and
84%,
respectively,
of
the
control
levels
for
mid
dose
males,
79%
and
79%,
respectively,
for
mid
dose
females,
60%
and
73%,
respectively
for
highdose
males,
and
63
and
75%,
respectively,
for
high
dose
females.
Body
weight
gains
by
all
treated
groups
were
similar
to
the
controls
during
lactation
days
11
21.
Except
for
mid
and
high
dose
females,
postweaning,
body
weight
gains
were
similar
between
the
treated
and
control
groups.
Body
weight
differences
for
high
dose
dams
were
10%
less
at
the
beginning
of
lactation
and
recovered
to
6%
less
by
the
end
of
the
study.
The
high
dose
group
had
a
greater
number
of
stillborn
pups
as
indicated
by
a
live
birth
index
of
77%
compared
with
99%
for
the
control
group.
In
addition,
nine
high
dose
litters
either
died
or
were
sacrificed
moribund
on
lactation
days
1
4.
This
resulted
in
a
viability
index
for
the
high
dose
group
of
71%
compared
with
89%
for
the
controls.
Pup
mortality
in
the
mid
and
high
dose
groups
in
litters
surviving
to
weaning
was
greater
before
day
4
than
in
controls
[
3
pups
in
2/
20
controls;
18
pups
in
8/
22
litters,
mid
dose;
14
pups
in
4/
15
litters,
high
dose].
Survival
was
not
affected
at
any
time
in
the
low
dose
group
as
compared
with
the
control
group.
No
dose
or
treatment
related
differences
were
observed
between
treated
and
control
groups
for
duration
of
gestation,
number
of
pups/
litter
on
day
1,
or
per
cent
male
offspring.
At
necropsy,
no
treatment
related
gross
abnormalities
were
observed
in
the
dams
or
offspring.
Absolute
and
relative
liver
and
kidney
weights
of
the
offspring
were
not
affected
by
treatment.
A
few
clinical
signs
were
observed
in
high
dose
dams
and
pups;
increased
reactivity
to
handling
in
dams
on
weeks
2
and
3
of
dosing,
and
slower
surface
righting
in
pups
on
day
4.
There
were
no
effects
on
measures
of
physical
or
sexual
development.
There
was
an
increase
in
motor
activity
at
the
mid
and
high
dose
during
lactation
in
both
sexes.
Some
decrease
in
habituation
of
motor
activity
in
females
on
day
22
was
also
seen.
While
there
was
no
effect
on
auditory
startle
reflex
amplitudes,
there
was
a
clear
reduction
in
auditory
startle
response
habituation
in
both
sexes
at
the
high
dose
on
day
28
and
on
day
60.
Slight
decreases
in
absolute,
but
not
relative,
brain
weights
in
mid
and
high
dose
female
pups
were
observed
on
postnatal
day
11
(9
10%)
but
narrowed
to
3
5%
less
by
day
65.
Brain
lengths
and
widths
were
Lindane/
September
2000
RED
Toxicology
Chapter
28
similar
between
the
treated
and
control
pups.
Morphometric
brain
measurements
did
not
show
any
significant
differences
in
the
sizes
of
the
neocortex,
hippocampus,
corpus
callosum,
or
cerebellum
on
days
11
or
65.
There
were
no
effects
on
histopathology
of
the
nervous
system.
The
maternal
toxicity
LOAEL
is
120
ppm
(13.7
mg/
kg/
day)
based
on
decreased
body
weight
gains,
decreased
food
consumption,
and
increased
reactivity
to
handling.
The
maternal
toxicity
NOAEL
is
50
ppm
(5.
6
mg/
kg/
day).
The
offspring
toxicity
LOAEL
is
50
ppm
(5.6
mg/
kg/
day)
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
The
offspring
toxicity
NOAEL
is
10
ppm
(1.2
mg/
kg/
day).
This
study
is
classified
as
Unacceptable/
Guideline
[870.6300
(§
83
6)]
since
laboratory
validation
studies
of
the
neurobehavioral
tests
were
not
included,
but
it
may
be
upgraded
and
found
acceptable
if
this
information
is
obtained.
The
number
of
animals
tested
at
the
highest
dose
is
only
6
compared
to
the
required
number
of
10
animals
per
dose.
4.9
Metabolism
Adequacy
of
data
base
for
metabolism:
The
data
base
formetabolismis
considered
tobe
complete.
No
additional
studies
are
required
at
this
time.
Lindane
is
distributed
to
all
organs
at
measurable
concentrations
within
a
few
hours
after
oral
administration.
The
highest
concentrations
are
found
in
adipose
tissue.
The
metabolism
of
lindane
is
initiated
through
one
of
pathways:
Dehydrogenation
leading
to
HCH,
Dehydrochlorination
leading
to
formation
of
PCCH,
Dechlorination
leading
to
formation
of
tetrachlorohexene,
or
Hydroxylation
leading
to
formation
of
hexachlorocyclohexanol.
Further
metabolismleads
to
a
large
number
of
metabolites.
Volatilizalion
appears
to
be
an
important
route
of
its
dissipation
under
the
high
temperature
conditions
of
tropical
regions.
Lindane
is
converted
by
enzymatic
reactions,
mainly
in
the
liver.
In
mammals,
including
humans,
lindane
is
excreted
very
rapidly
in
urine
and
faeces
after
metabolic
degradation;
only
small
amounts
are
eliminated
unchanged.
The
half
life
of
lindane
administered
to
rats
is
2
4
days
depending
on
the
frequency
of
exposures,
single
or
repeated.
870.7600
Dermal
Absorption
Rat
EXECUTIVE
SUMMARY:
In
a
dermal
absorption
study,
(MRID
40056107)
24
male
Crl:
CD
®
(SD)
BRrats
per
group
received
dermal
applications
of
lindane
20%
emulsifiable
concentrate
([
14
C]
Lindane
and
unlabeled
Lindane)
at
doses
of
0.
1,
1.
0,
or
10
mg/
rat.
Four
animals/
group
were
bled
and
sacrificed
at
intervals
of
0.
5,
1,
2,
4,
10,
or
24
hours
after
application
of
the
test
article.
Quantities
absorbed
increased
with
dose
and
duration
of
exposure
while
percent
absorbed
Lindane/
September
2000
RED
Toxicology
Chapter
29
increased
with
time
and
decreased
with
dose.
Percents
of
the
low,
mid,
and
high
doses
absorbed
were
0.6,
0.96,
and
0.
66%
after
0.
5
hours;
18.07,
8.31,
and
2.
81%
after
10
hours;
and
then,
increased
to
27.72,
20.86,
and
5.
05%
after
24
hours.
The
total
amount
of
test
article
absorbed
after
24
hours,
as
calculated
from
urine,
feces,
and
carcass,
was
0.
028,
0.21,
and
0.
51
mg
for
the
low,
mid,
and
high
dose
groups,
respectively.
The
process
appears
to
be
approaching
saturation
at
the
high
dose.
Recovered
radioactivity
(absorbed,
skin,
skin
rinse,
filter
paper
and
spreader)
was
74.19,
70.19
and
58.35%
of
the
applied
dose
after
24
hours
of
exposure
in
the
low,
mid,
and
high
dose,
respectively.
This
study
is
considered
Acceptable/
guideline
and
satisfies
the
requirements
for
a
dermal
absorption
study
in
rats
[85
2].
EXECUTIVE
SUMMARY:
In
a
dermal
absorption
study,
(MRID
40056108)
24
male
Hra:(
NZW)
SPF
rabbits
per
group
received
dermal
applications
of
lindane
20%
emulsifiable
concentrate
([
14
C]
Lindane
and
unlabeled
Lindane)
at
doses
of
0.
5,
5.
0,
or
50
mg/
rabbit.
Four
animals/
group
were
bled
and
sacrificed
at
intervals
of
0.
5,
1,
2,
4,
10,
or
24
hours
after
application
of
the
test
article.
Quantities
absorbed
increased
with
dose
and
duration
of
exposure
while
percent
absorbed
increased
with
time
and
decreased
with
dose.
Percentages
of
the
low,
mid,
and
high
doses
absorbed
were
5.97,
6.68,
and
1.
99%
after
0.
5
hours
;
51.68,
23.76
and
10.96%
after
10
hours;
and
then
increased
to
55.68,
39.99,
and
16.56%
after
24
hours.
The
total
amount
of
test
article
absorbed
after
24
hours,
as
calculated
fromurine,
feces,
and
carcass,
was
0.
28,
2.00,
and
8.
46
mg
for
the
low,
mid,
and
high
dose
groups,
respectively.
The
original
DER
states
that
no
evidence
of
saturation
of
the
absorption
process
was
observed;
however
upon
further
examination
it
appears
that
there
is
evidence
of
saturation
at
the
highest
dose
(50
mg/
rabbit)
tested.
Recovered
radioactivity
(absorbed,
skin,
skin
rinse,
filter
paper
and
spreader)
was
82.01,
78.27
and
66.34%
of
the
applied
dose
after
24
hours
of
exposure
in
the
low,
mid,
and
high
dose,
respectively.
This
study
is
considered
Acceptable/
guideline
and
satisfies
the
requirements
for
a
dermal
absorption
study
in
rabbits
[85
2].
However,
it
should
be
noted
that
the
rabbit
is
not
the
preferred
species
for
dermal
absorption
studies
as
it
grossly
overestimates
absorption
compared
to
man.
5.
0
TOXICITY
ENDPOINT
SELECTION
5.1
See
Section
9.
2
for
Endpoint
Selection
Table.
5.2
Dermal
Absorption
Dermal
Absorption
Factor:
10
%
The
HIARC
concurred
with
the
TES
committee
decision
(HED
Doc.
#
013460)
that
the
dermal
absorption
factor
is
10%
based
on
a
published
report
by
Feldman
and
Maibach
(Toxicology
and
Applied
Pharmacology
28,
126
132,
1974).
Lindane/
September
2000
RED
Toxicology
Chapter
30
The
Maibach
study
tested
12
pesticides
and
herbicides,
including
lindane,
on
human
subjects
(6
per
chemical)
to
quantitate
their
dermal
penetration.
C
14
labeled
chemicals
were
applied
topically
(4
g/
cm
2
)
to
the
forearm
or
via
the
intravenous
route
(1
Ci).
Excretion
of
the
chemicals
was
then
monitored
by
collecting
and
analyzing
urine
samples
during
the
5
day
testing
period.
All
results
were
calculated
as
percent
of
the
injected
or
applied
dose.
Data
obtained
after
IV
dosing
was
used
to
correct
the
skin
penetration
data
for
incomplete
urinary
recovery.
Lindane
was
shown
to
have
a
penetration
factor
of
9.3%
±
3.
7
(SD).
The
dermal
absorption
factor
is
required
for
dermal
exposure
for
all
durations
of
exposure
risk
assessment
since
oral
doses
were
selected
for
these
exposure
periods.
5.3
Classification
of
Carcinogenic
Potential
The
classification
of
carcinogenic
potential
will
be
re
evaluated
upon
receipt
of
a
new
mouse
carcinogenicity
study,
expected
in
December
2000.
Currently,
according
to
the
TES
committee
report
(1994,
Doc
013460),
lindane
has
not
been
classified
by
the
HED
Cancer
Peer
Review
Committee.
The
RfD/
Peer
Review
Committee
in
1993
concluded
that:
"The
mouse
carcinogenicity
data
were
considered
insufficient
because
of
major
deficiencies
associated
with
all
studies
available."
Lindane
however
had
been
previously
(1985)
classified
by
the
Cancer
Assessment
Group
of
the
Office
of
Research
and
Development
as
a
group
B2/
C
carcinogen
based
on
increased
incidence
of
mouse
liver
tumors.
Although
the
animal
data
was
limited,
the
presence
of
a
carcinogenic
metabolite,
2,4,6
trichlorophenol,
in
meaningful
quantities
in
the
urine
of
humans
exposed
to
lindane
and
the
structural
similarity
with
a
rodent
carcinogen,
alpha
hexachlorocyclohexane,
elevated
the
classification
above
a
"C"
to
"B2".
The
upper
bound
slope
of
the
dose
response
was
Q1*
=
1.
1
(mg/
kg/
day)
1
.
6.0
FQPA
CONSIDERATIONS
6.1
Special
Sensitivity
to
Infants
and
Children
Although
the
developmental
study
in
rats
provided
no
indication
of
a
quantitative
increased
susceptibility/
sensitivity
following
in
utero
exposure
to
lindane,
evidence
of
a
qualitative
increase
in
susceptibility
was
noted
in
the
developmental
neurotoxicity
study
and
the
2
generation
reproductive
study
in
rats.
Therefore,
the
FQPAcommittee
decided
to
reduce
the
safety
factor
to
3X
for
lindane.
In
the
prenatal
developmental
toxicity
studies
in
rats,
developmental
effects
were
observed
only
at
or
above
doses
causing
maternal
toxicity.
The
prenatal
developmental
study
in
rabbits
is
classified
as
Unacceptable
(not
upgradable)
since
maternal
and
developmental
toxicityLOAELs
were
not
identified
and
the
highest
dose
did
not
approach
the
limit
dose.
Therefore,
dose
selection
was
considered
inadequate.
Doses
were
based
on
the
results
of
a
subcutaneous
studyin
the
rabbit
(MRID
00062658)
which
is
not
a
valid
method
for
selecting
doses
for
an
oral
study.
Several
other
deficiencies
were
noted
in
the
conduct
of
this
study,
included:
percent
purity
of
the
test
article
was
Lindane/
September
2000
RED
Toxicology
Chapter
31
not
given,
dosing
solutions
were
not
analyzed
for
concentration,
stability,
or
homogeneity,
and
much
of
the
individual
animal
data
were
not
included.
Although
the
developmental
toxicitystudyin
rabbits
was
classified
unacceptable,
the
HIARC
concluded
that
a
new
study
is
not
required
because:
1)
The
developmental
toxicity
study
in
rabbits
and
rats
using
a
subcutaneous
route
of
administration
shows
no
developmental
effects
at
the
maternally
toxic
dose;
2)
The
incidences
of
skeletal
effects
observed
in
the
developmental
toxicity
study
in
rats,
with
gavage
as
the
route
of
administration,
are
within
historical
controls;
3)
More
severe
maternal
effects
are
seen
in
the
rabbit
study
with
subcutaneous
administration;
4)
The
rat
appears
to
be
the
more
sensitive
species
for
developmental
effects;
5)
Adevelopmental
neurotoxicity
study
has
already
been
submitted.
There
was,
however,
evidence
of
qualitative
increased
susceptibility
in
the
rat
multi
generation
reproduction
study:
Both
parental
and
offspring
LOAELS
are
13
mg/
kg;
however
there
is
a
qualitative
difference
in
the
severity
of
effects.
In
the
parental
animals,
toxicity
was
seen
in
the
form
of
reduction
in
body
weight
gain
during
gestation
while
offspring
toxicity
was
correlated
with
decreases
in
pup
viability
and
pup
body
weight
in
the
F1
and
F2
generations
as
well
as
delayed
maturation
in
the
F2
generation.
Evidence
for
quantitative
increase
in
susceptibility
could
not
be
ascertained
due
to
the
wide
spread
in
the
doses
tested.
There
is
also
quantitative
increased
susceptibility
demonstrated
in
the
rat
developmental
neurotoxicity
study:
Maternal
toxicity
observed
at
120
ppm
(13.7
mg/
kg/
day,
LOAEL)
is
based
on
decreased
body
weight
gains,
decreased
food
consumption,
and
increased
reactivity
to
handling
(maternal
NOAEL
is
50
ppm;
5.
6
mg/
kg/
day).
Offspring
toxicity
was
observed
at
50
ppm
(5.
6
mg/
kg/
day,
LOAEL)
and
is
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation
(NOAEL
is
10
ppm;
1.
2
mg/
kg/
day).
The
offspring
effects
seen
in
the
developmental
neurotoxicity
study
were
the
same
as
those
seen
in
the
the
two
generation
reproduction
study
no
additional
functional
or
morphological
changes
in
the
nervous
system
were
noted.
In
the
open
literature,
lindane
is
found
in
mother's
milk
and
metabolites
of
lindane
have
been
shown
to
cross
the
placental
barrier.
6.2
Recommendation
for
a
Developmental
Neurotoxicity
Study
A
developmental
neurotoxicity
study
has
already
been
conducted.
Lindane/
September
2000
RED
Toxicology
Chapter
32
7.
0
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September
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in
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126
132
(1974).
Lindane/
September
2000
RED
Toxicology
Chapter
35
Wolff,
G.
L.,
Roberts,
D.
W.,
Morrissey,
R.
L.,
Greenman,
D.
L.,
Allen,
R.
R.,
Campbell,
W.
L.,
Bergman,
H.,
Nesnow,
S.,
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H.
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Lindane/
September
2000
RED
Toxicology
Chapter
36
8.
0
APPENDICES
Tables
for
Use
in
Risk
Assessment
Lindane/
September
2000
RED
Toxicology
Chapter
37
8.1
Toxicity
Profile
Summary
Tables
8.1.1
Acute
Toxicity
Table
See
Section
4.
1
8.1.2
Subchronic,
Chronic
and
Other
Toxicity
Tables
Table
1
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
870.3250
90
Day
dermal
toxicity
41427601
acceptable/
guideline
1990
NOAEL
=
60
mg/
kg/
day
LOAEL
=
10
mg/
kg/
day
based
on
lesion
in
the
liver
in
males
and
females
and
adrenal
gland
weight
increases
in
males
870.3465
90
Day
inhalation
toxicity
00255003
acceptable/
guideline
1983
NOAEL
=
0.
025
mg/
kg/
day
LOAEL
=
0.
13
mg/
kg/
day
based
on
transient
microscopic
lesions
in
the
kidney
and
increased
kidney
weights
in
the
males.
40873501
acceptable/
guideline
1988
NOAEL
=
0.
08
mg/
kg/
day
LOAEL
=
0.
25
mg/
kg/
day
based
on
death
of
one
male
and
one
female
870.3700a
Prenatal
developmental
in
rat
00062656
(Subcutaneous)
unacceptable/
nonguideline
1976
Maternal
NOAEL
=
5
mg/
kg/
day
LOAEL
=
15
mg/
kg/
day
based
on
reduced
body
weight
Developmental
NOAEL
=
>30
mg/
kg/
day
LOAEL
=
not
identified
42808001
acceptable/
guideline
1971
Maternal
NOAEL
=
5
mg/
kg/
day
LOAEL
=
10
mg/
kg/
day
based
on
reduced
body
weight
and
food
consumption
Developmental
NOAEL
=
10
mg/
kg/
day
LOAEL
=
20
mg/
kg/
day
based
on
skeletal
variation.
870.3700b
Prenatal
developmental
in
rabbit
00062658
(Subcutaneous)
unacceptable/
nonguideline
1976
Maternal
NOAEL
=
5
mg/
kg/
day
LOAEL
=
15
mg/
kg/
day
based
on
clinical
signs,
mortality,
reduced
body
weight
Developmental
NOAEL
15
mg/
kg/
day
LOAEL
=
not
identified
42808002
unacceptable/
nonguideline
1971
Maternal
NOAEL
20
mg/
kg/
day
LOAEL
=
not
identified
Developmental
NOAEL
20
mg/
kg/
day
LOAEL
=
not
identified
Lindane/
September
2000
RED
Toxicology
Chapter
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
38
870.3800
Reproduction
and
fertility
effects
42246101
acceptable/
guideline
1991
NOAEL
=
1.
7
mg/
kg/
day
;
0.
09mg/
kg/
day
LOAEL
=
13
mg/
kg/
day
based
on
reduced
body
weight
;
1.
7
mg/
kg/
day
based
on
increased
kidney
weight
and
alpha
2
globulin
accumulation
870.4100a
Chronic
toxicity
rodents
870.4200
Carcinogenicity
rats
41094101
41853701
42891201
acceptable/
guideline
1993
NOAEL
=0.
6
mg/
kg/
day
LOAEL
=
4.
8
mg/
kg/
day
;
6
mg/
kg/
day
based
on
periacinar
hepatocyte
hypertrophy,
increased
liver
and
spleen
weights,
and
decreased
platelets
no
evidence
of
carcinogenicity
870.4300
Carcinogenicity
mice
special
study
1987
NOAEL
=
not
identified
LOAEL
=
23
mg/
kg/
day
based
on
induction
of
tumors,
increased
liver
weights,
increased
enzyme
activity,
and
irreversible
Clara
cell
hyperplasia
in
lung
evidence
of
carcinogenicity
liver
and
lung
tumors
870.5300
Gene
Mutation
Mammalian
Cell
00144500
unacceptable/
guideline
1985
negative
870.5915
In
Vivo
Sister
Chromatid
Exchange
00024504
unacceptable
guideline
1984
negative
870.5450
dominant
lethal
assay
00062657
unacceptable
guideline
negative
870.6200a
Acute
neurotoxicity
screening
battery
44769201
acceptable/
guideline
1999
NOAEL
=
6
mg/
kg/
day
;
20
mg/
kg/
day
LOAEL
=
20
mg/
kg/
day
based
on
icreased
grip
strength
and
motor
activity.
60
mg/
kg/
day
based
on
tremors,
convulsions,
decreased
motor
activity
and
increased
grip
strngth.
870.6200b
Subchronic
neurotoxicity
screening
battery
44781101
acceptable/
guideline
1999
NOAEL
=
7.
9
mg/
kg/
day
;
7.
1
mg/
kg/
day
LOAEL
=
30.
2
mg/
kg/
day
and
28.
1
mg/
kg/
day
based
on
hypersensitivity
to
touch
and
hunched
posture
Lindane/
September
2000
RED
Toxicology
Chapter
Guideline
No./
Study
Type
MRID
No.
(year)/
Classification
/Doses
Results
39
870.6300
Developmental
neurotoxicity
45073501
unacceptable/
guideline
1999
Maternal
NOAEL
=
5.
6
mg/
kg/
day
LOAEL
=
13.
7
mg/
kg/
day
based
on
decreased
body
weight
gains,
decreased
food
consumption,
and
increased
reactivity
to
handling.
Offspring
NOAEL
=
1.
2
mg/
kg/
day
LOAEL
=
5.
6
mg/
kg/
day
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
870.7600
Dermal
penetration
40056107
rat
40056108
rabbit
acceptable/
guideline
1987
18
%
absorption
at
10
hours
Lindane/
September
2000
RED
Toxicology
Chapter
40
Table
2
Summary
of
Toxicological
Dose
and
Endpoints
for
LINDANE
for
Use
in
Human
Risk
Assessment
1
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
females
13
50
years
of
age
not
applicable;
no
relevant
single
exposure
endpoint
was
identified
Acute
Dietary
general
population
including
infants
and
children
NOAEL=
6
mg/
kg/
day
UF
=
100
Acute
RfD
=
0.06
mg/
kg/
day
FQPA
SF
=
3
aPAD
=
acute
RfD
FQPA
SF
=
0.
02
mg/
kg/
day
Acute
Neurotoxicity
in
Rats/
MRID
44769201
LOAEL
is
20
mg/
kg
based
on
increased
grip
strength,
increased
Motor
Activity
Chronic
Dietary
all
populations
NOAEL=
0.47
mg/
kg/
day
UF
=
100
Chronic
RfD
=
0.
0047
mg/
kg/
day
FQPA
SF
=
3
cPAD
=chrRfD
FQPA
SF
=
0.
0016
mg/
kg/
day
Chronic
Feeding
and
Carcinogenicity
in
Rats
MRID
41094101,
41853701,
42891201
LOAEL
is
4.
81
mg/
kg/
day
based
on
periacinar
hepatocyte
hypertrophy,
increased
liver/
spleen
weigt,
increased
platelets
Short
Term
Dermal
(1
7
days)
(Occupational/
Residential)
oral
study
NOAEL=
1.
2
mg/
kg/
day
(dermal
absorption
rate
=
10%
)
LOC
for
MOE
=
100
(Occupational)
no
residential
exposure
expected
Developmental
Neurotoxicity
Study
in
Rats
(MRID
45073501)
LOAEL
is
5.
6
mg/
kg/
day
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation
Lindane/
September
2000
RED
Toxicology
Chapter
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
FQPA
SF
and
Endpoint
for
Risk
Assessment
Study
and
Toxicological
Effects
41
Intermediate
Term
Dermal
(1
week
several
months)
(Occupational)
oral
study
NOAEL=
1.
2
mg/
kg/
day
(dermal
absorption
rate
=
10%
)
LOC
for
MOE
=
100
(Occupational)
Developmental
Neurotoxicity
Study
in
Rats
(MRID
45073501)
LOAEL
is
5.
6
mg/
kg/
day
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
Long
Term
Dermal
(several
months
lifetime)
(Occupational)
oral
study
NOAEL=
0.47
mg/
kg/
day
(dermal
absorption
rate
=
10%
)
LOC
for
MOE
=
100
(Occupational)
Chronic
Feeding
and
Carcinogenicity
in
Rats
MRID
41094101,
41853701,
42891201
LOAEL
is
4.
81
mg/
kg/
day
based
on
periacinar
hepatocyte
hypertrophy,
increased
liver/
spleen
weigt,
increased
platelets
Short
Term
Inhalation
(1
7
days)
(Occupational)
inhalation
study
LOAEL=
0.13
mg/
kg/
day
LOC
for
MOE
=
100
(Occupational)
90
Day
Inhalation
Toxicity
MRID
00255003
based
on
clinical
signs
(diarrhea,
piloerection)
seen
at
day
14
and
continuing
for
20
days.
Intermediate
Term
Inhalation
(1
week
several
months)
(Occupational)
inhalation
study
NOAEL=
0.025
mg/
kg/
day
LOC
for
MOE
=
100
(Occupational)
90
Day
Inhalation
Toxicity
MRID
00255003
LOAEL
is
0.
13
mg/
kg/
day
based
on
micro
lesions
in
kidney,
increased
kidney
weight
Cancer
(oral)
group
B2/
C
carcinogen
Q1*
=
1.1
(mg/
kg/
day)
1
based
on
increased
incidence
of
mouse
liver
tumors
1
UF
=
uncertainty
factor,
FQPA
SF
=
FQPA
safety
factor,
NOAEL
=
no
observed
adverse
effect
level,
LOAEL
=
lowest
observed
adverse
effect
level,
PAD
=
population
adjusted
dose
(a
=
acute,
c
=
chronic)
RfD
=
reference
dose,
LOC
=
level
of
concern,
MOE
=
margin
of
exposure
Lindane/
September
2000
RED
Toxicology
Chapter
42
SignOff
Date:
9/
28/
00
DP
Barcode:
D269338
HED
DOC
Number:
014351
Toxicology
Branch:
RRB4
| epa | 2024-06-07T20:31:43.095708 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0202-0008/content.txt"
} |
EPA-HQ-OPP-2002-0202-0009 | Supporting & Related Material | "2002-08-14T04:00:00" | null | HED
DOC.
NO.
014272
August
2,
2000
MEMORANDUM
SUBJECT:
LINDANE
Report
of
the
FQPA
Safety
Factor
Committee
FROM:
Brenda
Tarplee,
Executive
Secretary
FQPA
Safety
Factor
Committee
Health
Effects
Division
(7509C)
THROUGH:
Ed
Zager,
Chairman
FQPA
Safety
Factor
Committee
Health
Effects
Division
(7509C)
TO:
Sue
Shallal,
Risk
Assessor
Reregistration
Branch
4
Health
Effects
Division
(7509C)
PC
Code:
009001
The
FQPA
Safety
Factor
Committee
met
on
July
24,
2000
to
evaluate
the
hazard
and
exposure
data
bases
for
lindane
and
concluded
that
the
FQPA
Safety
Factor
(as
required
by
Food
Quality
Protection
Act
of
August
3,
1996)
for
use
in
human
health
risk
assessment
be
reduced
to
3x.
2
I.
HAZARD
ASSESSMENT
(Memorandum:
S.
Shallal
to
M.
T.
Howard
dated
July
27,
2000)
A.
Adequacy
of
the
Toxicology
Database
There
are
two
developmental
studies
conducted
in
rats
and
rabbits
in
which
Lindane
is
administered
via
the
oral
and
subcutaneous
(4
studies
in
all).
Although
the
rabbit
studies
were
classified
as
unacceptable,
the
HIARC
concluded
that
a
new
developmental
toxicity
study
in
rabbits
is
not
required
(see
Section
I.
B.
below
or
refer
to
the
HIARC
document
for
details).
An
acceptable
2
generation
reproductive
study
is
also
available,
as
well
as,
acute,
subchronic
and
developmental
neurotoxicity
studies.
B.
Determination
of
Susceptibility
The
data
provided
no
indication
of
quantitative
or
qualitative
increased
susceptibility/
sensitivity
in
rats
following
in
utero
exposure
to
lindane.
In
the
prenatal
developmental
toxicity
studies
in
rats,
developmental
effects
were
observed
only
at
or
above
doses
causing
maternal
toxicity.
The
prenatal
developmental
study
in
rabbits
is
classified
as
Unacceptable
(not
upgradable)
since
maternal
and
developmental
toxicity
LOAELs
were
not
identified
and
the
highest
dose
did
not
approach
the
limit
dose.
Therefore,
dose
selection
was
considered
inadequate.
Doses
were
based
on
the
results
of
a
subcutaneous
study
in
the
rabbit
(MRID
00062658)
which
is
not
a
valid
method
for
selecting
doses
for
an
oral
study.
Several
other
deficiencies
were
noted
in
the
conduct
of
this
study:
percent
purity
of
the
test
article
was
not
given,
dosing
solutions
were
not
analyzed
for
concentration,
stability,
or
homogeneity,
and
much
of
the
individual
animal
data
were
not
included.
Although
the
developmental
toxicity
study
in
rabbits
was
classified
unacceptable,
the
HIARC
concluded
that
a
new
study
is
not
required
because:
1)
The
developmental
toxicity
study
in
rabbits
and
rats
using
a
subcutaneous
route
of
administration
shows
no
developmental
effects
at
the
maternally
toxic
dose;
2)
The
skeletal
effects
observed
in
the
developmental
toxicity
study
in
rats,
with
gavage
as
the
route
of
administration,
are
within
historical
controls;
3)
More
severe
maternal
effects
are
seen
in
the
rabbit
study
with
subcutaneous
administration;
4)
The
rat
appears
to
be
the
more
sensitive
species
for
developmental
effects;
5)
A
developmental
neurotoxicity
study
has
already
been
submitted.
There
was,
however,
evidence
of
qualitative
increased
susceptibility
in
the
rat
multigeneration
reproduction
study:
Both
parental
and
offspring
LOAELS
are
13
mg/
kg;
however
there
is
a
qualitative
difference
in
effects.
In
the
parental
animals,
toxicity
was
seen
in
the
form
of
reduction
in
body
weight
gain
during
gestation
while
offspring
toxicity
was
correlated
with
decreases
in
pup
viability
and
pup
body
weight
in
the
F1
and
F2
generations
as
well
as
delayed
3
maturation
in
the
F2
generation.
Evidence
for
quantitative
increase
in
susceptibility
could
not
be
ascertained
due
to
the
wide
spread
in
the
doses
tested.
There
is
also
quantitative
increased
susceptibility
demonstrated
in
the
rat
developmental
neurotoxicity
study:
Maternal
toxicity
observed
at
120
ppm
(13.7
mg/
kg/
day,
LOAEL)
is
based
on
decreased
body
weight
gains,
decreased
food
consumption,
and
increased
reactivity
to
handling
(maternal
NOAEL
is
50
ppm;
5.
6
mg/
kg/
day).
Offspring
toxicity
was
observed
at
50
ppm
(5.
6
mg/
kg/
day,
LOAEL)
and
is
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation
(NOAEL
is
10
ppm;
1.
2
mg/
kg/
day).
The
offspring
effects
seen
in
the
developmental
neurotoxicity
study
were
the
same
as
those
seen
in
the
the
two
generation
reproduction
study
no
additional
functional
or
morphological
hazards
to
the
nervous
system
were
noted.
C.
Studies
from
the
Literature
The
open
literature
does
contain
citations
which
suggest
an
increase
in
susceptibility
of
fetuses
and
young
animals
exposed
to
lindane.
The
transfer
of
lindane
via
mother's
milk
also
seems
to
be
efficient,
as
well
as,
its
metabolism
into
pentachlorobenzene
(refer
to
the
HIARC
document
for
details).
II.
EXPOSURE
ASSESSMENTS
A.
Dietary
(Food)
Exposure
Considerations
(Correspondence:
T.
Morton
to
B.
Tarplee
dated
July
15,
2000)
The
registrant
is
supporting
the
use
of
lindane
on
barley,
broccoli,
brussels
sprouts,
cabbage,
cauliflower,
corn,
lettuce,
oats,
radish,
rye,
sorghum,
spinach,
and
wheat.
Only
seed
treatment
uses
remain
on
the
label.
Seed
treatment
application
rates
range
from
0.
33
to
3.57
oz.
a.
i./
cwt
of
seed.
For
comparison,
the
3.57
oz.
a.
i./
cwt
application
rate
is
equivalent
to
0.04
lb.
a.
i./
acre.
Since
the
only
supported
use
is
seed
treatment,
application
is
made
only
once
per
season.
Tolerances
are
currently
established
for
residues
of
the
insecticide
lindane
(gamma
isomer
of
benzene
hexachloride)
in
or
on
many
raw
agricultural
commodities
at
levels
ranging
from
0.01ppm
(pecans)
to
7ppm
(meat
fat).
Codex
MRLs
range
from
0.
01
ppm
in
milk
to
3
ppm
in
cranberry
and
strawberry.
Codex
MRLs
for
supported
crops
in
the
US
are
0.
5
ppm
for
brussels
sprouts,
cabbage,
cauliflower,
and
cereal
grains;
0.
1
ppm
for
eggs;
2
ppm
for
head
lettuce,
meat
of
cattle,
pigs,
and
sheep,
and
spinach;
and
1
ppm
for
radish.
The
MARC
has
determined
that
until
adequate
seed
treatment
metabolism
studies
are
submitted,
the
total
radioactive
residues
will
be
used
for
risk
assessment
purposes.
In
a
4
confined
rotational
crop
study,
radioactive
lindane
was
found
in
barley
forage
but
not
barley
grain.
It
was
also
found
in
carrot
tops
and
to
a
lesser
extent
in
mature
lettuce.
No
monitoring
data
is
available
which
would
definitively
include
lindane
only
from
seed
treatment
uses.
However,
it
may
be
possible
to
use
available
monitoring
data
for
foliar
uses
on
imported
commodities.
Field
trials
were
conducted
on
wheat,
feeding
studies
on
ruminant
and
poultry,
but
will
not
be
used
since
the
MARC
has
concluded
that
the
total
radioactive
residues
must
be
used
for
risk
assessment
purposes.
In
1998,
BEAD
provided
percent
crop
treated
data
for
small
grains
(7
%
crop
treated),
field
corn
(6
%
crop
treated),
and
sorghum
(10
%
crop
treated).
HED
has
asked
BEAD
to
supply
current
%
crop
treated
data
for
the
above
crops
and
any
other
of
the
supported
crops.
The
Dietary
Exposure
Evaluation
Model
(DEEM)
is
used
to
estimate
the
dietary
risk
resulting
from
the
residues
of
lindane
on
foods.
The
DEEM
analyses
are
refined
using
the
available
%CT
data.
B.
Dietary
(Drinking
Water)
Exposure
Considerations
(Correspondence:
D.
Young
to
B.
Tarplee,
dated
July
10,
2000.)
The
environmental
fate
database
for
lindane
is
adequate
to
characterize
the
potential
for
contamination
of
drinking
water
sources.
These
data
indicate
that
parent
lindane
is
persistent
and
moderately
mobile.
It
is
transported
through
the
environment
by
both
hydrologic
and
atmospheric
means.
It
is
resistant
to
photolysis
and
hydrolysis
(except
at
high
pH),
and
degrades
very
slowly
by
microbial
actions
(980
day
soil
half
life).
Degradates
are
predominantly
benzene
hexachloride,
pentachlorocyclohexane,
1,2,4,trichlorobenzene
and
1,
2,
3
trichlorobenzene.
In
submitted
studies,
degradates
were
observed
at
much
less
than
10%
of
applied.
Currently,
U.
S.
agricultural
uses
of
lindane
are
restricted
to
seed
treatments,
and
application
rates
are
quite
low.
Even
under
these
restriction,
however,
lindane
may
reach
water
resources
at
levels
above
the
Maximum
Concentration
Level
(MCL
=
0.
2
µg/
L).
Monitoring
data
are
available
which
demonstrate
the
presence
of
lindane
in
the
environment:
In
the
U.
S.
EPA
STORET
data
base,
720
detections
(after
culling
of
data
to
eliminate
dubious
data,
e.
g.
K
and
U
codes)
in
ground
water
were
reported
between
the
years
1968
and
1995,
in
nearly
all
regions
of
the
country,
with
especially
high
numbers
of
detections
in
the
South
and
West.
For
these
720
detections,
the
median
and
mean
concentrations
were
0.01
and
11
µg/
L,
respectively.
For
surface
waters,
8775
detections
were
reported
with
median
and
mean
concentrations
of
0.
005
and
0.
18
µg/
L.
STORET
Detections
were
reported
in
nearly
all
regions
of
the
conterminous
U.
S.
In
the
USGS
NAWQA
study,
lindane
was
detected
in
2.
58%
of
surface
water
samples
5
(0.
67%
at
levels
greater
than
0.
05
mg/
L,
maximum
concentration
reported
was
0.
13
mg/
L).
For
groundwater,
USGS
NAWQA
reported
a
detection
frequency
of
0.
1
%
(0.
07%
at
levels
greater
than
0.
01
mg/
L,
maximum
concentration
reported
was
0.
032
mg/
L).
Since
all
monitoring
data
represent
detections
resulting
from
all
previous
uses
of
lindane
(including
foliar
uses
which
are
currently
not
supported
by
the
registrant),
models
were
used
to
calculate
the
estimated
environmental
concentrations
(EECs):
GENEEC
model
for
surface
water;
and
SCI
GROWfor
ground
water.
Due
to
the
persistence
of
lindane,
its
past
wide
spread
use,
and
its
mobility
by
both
atmospheric
at
hydrologic
means,
the
extent
of
population
exposed
could
be
high
in
comparison
to
other
chemicals.
C.
Residential
Exposure
Considerations
(Telephone
communication:
D.
Jaquith
on
July
19,
2000)
Only
seed
treatment
uses
remain
on
the
label
for
lindane.
There
are
no
registered
residential
uses
and
therefore,
residential
exposure
to
lindane
is
not
expected.
III.
SAFETY
FACTOR
RECOMMENDATION,
RATIONALE,
AND
APPLICATION
A.
Recommendation
of
the
Factor
The
Committee
recommended
that
the
FQPA
safety
factor
for
protection
of
infants
and
children
(as
required
by
FQPA)
should
be
reduced
to
3x
for
lindane.
B.
Rationale
for
the
Selection
of
the
FQPA
Safety
Factor
The
FQPA
SFC
concluded
that
a
safety
factor
is
required
for
lindane
since
there
is
evidence
of
increased
susceptibility
of
the
young
demonstrated
in
both
the
developmental
neurotoxicity
study
(quantitative)
and
the
2
generation
reproduction
study
in
rats
(qualitative).
The
Committee
recommended
that
the
FQPA
safety
factor
be
reduced
to
3x
because:
1)
the
toxicology
data
base
is
complete;
2)
the
available
data
provide
no
indication
of
quantitative
or
qualitative
increased
susceptibility
in
rats
from
in
utero
exposure
to
lindane
in
the
prenatal
developmental
study;
3)
although
the
developmental
toxicity
study
in
rabbits
was
classified
unacceptable,
the
HIARC
concluded
that
a
new
study
is
not
required
(See
Section
I.
B.);
4)
the
offspring
effects
seen
in
the
developmental
neurotoxicity
study
were
the
same
as
those
seen
in
the
the
two
generation
reproduction
study
(no
additional
functional
or
morphological
hazards
to
the
nervous
system
were
noted);
and
5)
adequate
actual
data,
surrogate
data,
and/
or
modeling
outputs
are
available
to
satisfactorily
assess
food
exposure
and
to
provide
a
screening
level
drinking
water
exposure
assessment;
and
6
6)
there
are
currently
no
residential
uses.
C.
Application
of
the
Safety
Factor
Population
Subgroups/
Risk
Assessment
Scenarios
The
FQPA
safety
factor
for
lindane
is
applicable
to
All
Population
Subgroups
for
Acute
and
Chronic
Dietary
Risk
Assessments
(there
are
currently
no
residential
scenarios),
since
there
is
concern
for
increased
susceptibility
of
the
young
demonstrated
in
the
developmental
neurotoxicity
study
and
in
the
2
generation
reproduction
study.
| epa | 2024-06-07T20:31:43.109631 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0202-0009/content.txt"
} |
EPA-HQ-OPP-2002-0202-0010 | Supporting & Related Material | "2002-08-14T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDE
AND
TOXIC
SUBSTANCES
HED
DOC.
NO.
014595
DATE:
June
18,
2001
MEMORANDUM
SUBJECT:
Lindane
(PC
Code:
009001)
A
Second
Report
of
the
Hazard
Identification
Assessment
Review
Committee.
FROM:
Suhair
Shallal,
Toxicologist.
Reregistration
Branch
4
Health
Effects
Division
(7509C)
THROUGH:
Elizabeth
Doyle,
Co
Chairman
and
Jess
Rowland,
Co
Chairman
Hazard
Identification
Assessment
Review
Committee
Health
Effects
Division
(7509C)
TO:
Mark
T.
Howard
Special
Review
and
Registration
Division
On
May
22,
2001,
the
Health
Effects
Division
(HED)
Hazard
Identification
Assessment
Review
Committee
(HIARC)
met
to
reconsider
the
endpoint
for
occupation
risk
assessment
for
the
inhalation
route
of
exposure.
Previouslythe
endpoint
was
based
on
kidneylesions
and
increased
kidney
weights
resulting
fromthe
accumulation
of
alpha
2
globulin.
These
effects
have
been
deemed
not
relevant
for
human
risk
assessment.
The
Committee's
decision
is
presented
in
this
report
along
with
the
previously
conclusions
of
the
June
13,
2000
HIARC
meeting.
In
that
meeting
the
Reference
Dose
(RfD)
and
the
toxicological
endpoints
for
acute
and
chronic
dietary,
as
well
as,
occupational
exposure
risk
assessments
were
selected.
HIARC
re
assessed
the
Reference
Dose
(RfD)
established
in
1994,
as
well
as
the
toxicological
endpoints
selected
for
acute
dietary
and
occupational/
residential
exposure
risk
assessments.
The
HIARC
also
addressed
the
potential
enhanced
sensitivity
of
infants
and
children
from
exposure
to
lindane
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
This
Report
has
been
revised
to
reflect
a
change
in
the
endpoint
selection
for
occupational
risk
assessment
through
the
inhalation
route
of
exposure.
2
1996.
Committee
Members
in
Attendance
Members
present
were:
Elizabeth
Doyle
David
Nixon
Jess
Rowland
Elizabeth
Mendez
William
Burnam
Pamela
Hurley
Yung
Yang
Brenda
Tarplee
Jonathan
Chen
Paula
Deschamp
Member(
s)
in
absentia:
Ayaad
Assaad
Data
was
presented
by
Suhair
Shallal
of
the
Reregistration
Branch
4.
Also
in
attendance
were:
Susan
Henley,
Whang
Phang,
Joseph
Nevola
Data
Presentation:
and
Suhair
Shallal,
Report
Presentation
Toxicologist
Report
Concurrence:
Brenda
Tarplee
Executive
Secretary
cc:
RD
Casewell
file
3
I.
INTRODUCTION
On
May
22,
2001,
the
Health
Effects
Division
(HED)
Hazard
Identification
Assessment
Review
Committee
(HIARC)
met
to
reconsider
the
endpoint
for
occupation
risk
assessment
for
the
inhalation
route
of
exposure.
Previously
the
endpoint
was
based
on
kidney
lesions
and
increased
kidney
weights
resulting
from
the
accumulation
of
alpha
2
globulin.
These
effects
have
been
deemed
not
relevant
for
human
risk
assessment.
The
Committee's
decision
is
presented
in
this
report
along
with
the
previously
conclusions
of
the
June
13,
2000
HIARC
meeting.
In
that
meeting
the
Reference
Dose
(RfD)
and
the
toxicological
endpoints
for
acute
and
chronic
dietary,
as
well
as,
occupational
exposure
risk
assessments
were
selected.
HIARC
re
assessed
the
Reference
Dose
(RfD)
established
in
1994,
as
well
as
the
toxicological
endpoints
selected
for
acute
dietary
and
occupational/
residential
exposure
risk
assessments.
The
HIARC
also
addressed
the
potential
enhanced
sensitivity
of
infants
and
children
from
exposure
to
lindane
as
required
by
the
Food
Quality
Protection
Act
(FQPA)
of
1996.
II.
HAZARD
IDENTIFICATION
A.
Acute
Reference
Dose
(RfD)*
General
population
Selected
Study:
Acute
Neurotoxicity
Study
Guideline
#:
OPPTS
870.6200
[§
81
8]
MRID
No.:
44769201
Executive
Summary:
In
an
acute
oral
neurotoxicity
study,
groups
of
10
Crl:
CD®
BR
rats/
sex/
dose
were
administered
single
dose
of
Lindane
(Batch
No.
HLS96/
1,
Purity
99.78%)
by
gavage
at
concentrations
of
0
(control),
6,
20,
or
60
mg/
kg.
Functional
observational
battery
(FOB)
and
motor
activity
(MA)
testing
were
performed
prior
to
administration
and
within
3
hours
(time
of
peak
effect)
of
dosing
(day
0),
and
on
days
7
and
14
post
dose.
Body
weights
were
recorded
pre
test,
weeklyduring
the
study
period
and
on
FOBassessment
days.
Clinical
signs
were
recorded
at
least
once
daily.
At
study
termination
all
animals
were
sacrificed
and
fixed
by
whole
body
perfusion,
designated
tissues
of
the
nervous
system
were
processed
for
microscopic
neuropathological
evaluation.
All
animals
survived
to
scheduled
termination.
One
male
in
the
60
mg/
kg
group
was
observed
to
convulse
on
the
day
of
treatment
within
2.75
hours
after
dosing.
Clinical
signs
were
also
observed
in
females
treated
at
60
mg/
kg
within
24
hours
of
dosing
and
included:
staining
of
the
fur,
stained
urogenital
region,
hunched
posture,
and
piloerection.
These
effects
in
females
persisted
for
four
days.
Significant
treatment
related
decreases
in
body
weight
gains
were
observed
for
males
in
the
60
mg/
kg
group
compared
to
the
control
group
for
the
first
week
of
the
study.
Females
administered
this
concentration
also
had
slightly
lower
body
weight
gains
throughout
the
study.
Food
consumption
for
males
and
females
administered
60
mg/
kg
was
significantly
decreased
compared
to
controls
for
Week
1
of
the
study.
Food
conversion
4
Acute
RfD
=
NOAEL
(mg/
kg)
=6=
0.
06mg/
kg
UF
100
ratios
in
the
treated
groups
were
not
changed
compared
to
control
groups.
At
the
first
FOB
assessment
on
Day
0
(3
hours
aft
er
dosing)
males
and
females
in
the
60
mg/
kg
group
exhibited
piloerection
(1
,2
),
decreased
rectal
temperature
(1
,1
),
increased
hindlimb
foot
splay
and
hunched
posture
(4
,7
).
Among
males
dosed
at
60
mg/
kg,
increased
respiration
(3)
and
tremor/
twitching
(1)
were
observed.
Females
administered
60
mg/
kg
were
observed
to
have
increased
incidences
of
walking
on
tip
toes
(10),
licking
behavior
(3),
decreased
foot
splay
(3)
and
an
absence
of
grooming
(8)
behavior.
Females
in
the
20
mg/
kg
also
had
decreased
grooming
(3)
behavior
and
increased
forelimb
grip
strength
(2).
Motor
activity
was
significantly
decreased
for
males
and
females
treated
with
60
mg/
kg
as
well
as
among
females
treated
with
20
mg/
kg
three
hours
post
treatment.
The
6
mg/
kg
group
remained
comparable
to
controls
in
FOB
assessment
parameters
and
MA.
No
neuropathological
changes
were
observed
during
the
histological
examinations
of
the
peripheral
or
central
nervous
systems
of
these
animals
at
any
exposure
concentration.
The
NOAEL
for
systemic
toxicity
is
20
mg/
kg
for
males
and
6
mg/
kg
for
females.
Based
on
the
substance
related
effects
on
body
weight,
body
weight
gain,
food
consumption,
and
clinical
signs
of
toxicity
the
LOAEL
for
systemic
toxicity
in
males
is
60
mg/
kg.
The
LOAEL
for
females
is
20
mg/
kg
based
on
a
lower
incidence
of
grooming
behavior
and
decreased
locomotor
activity
immediately
after
dosing,
in
addition
to
the
parameters
mentioned
above.
The
NOAEL
for
neurotoxic
effects
is
6
mg/
kg
for
females
and
the
LOAEL
is
20
mg/
kg
based
on
increased
forelimb
grip
strength
and
decreased
grooming
behavior
and
motor
activity
(MA).
The
NOAEL
for
neurotoxicity
in
males
is
20
mg/
kg
and
the
LOAEL
for
males
is
60
mg/
kg
based
on
tremors,
convulsions,
decreased
MA,
and
increased
forelimb
grip
strength.
This
study
is
classified
Acceptable/
guideline
and
satisfies
the
Subdivision
F
guideline
requirement
for
an
acute
oral
neurotoxicity
study
(§
81
8)
in
rats.
Dose
and
Endpoint
for
Establishing
an
Acute
RfD:
The
NOAEL
is
6
mg/
kg
based
on
increased
forelimb
grip
strength
and
decreased
grooming
behavior
and
motor
activity
in
female
rats
Uncertainty
Factor(
s):
100
;
10X
intraspecies
variations
and
10X
interspecies
etrapolation
Comments
about
Study/
Endpoint/
Uncertainty
Factor(
s):
5
Acute
Reference
Dose
(RfD)*
Females
(13
50
years)
An
appropriate
endpoint
attributable
to
a
single
dose
could
not
be
ascertained
fromeither
the
developmental
toxicity
study
in
rats
and
in
rabbits
or
in
the
developmental
neurotoxicity
study.
Although,
there
was
evidence
of
increased
susceptibility
in
the
DNT,
the
offspring
effects
were
not
attributable
to
a
single
dose.
A
separate
endpoint
for
this
subpopulation
was
therefore
not
identified.
2.2
Chronic
Reference
Dose
(RfD)
Selected
Study:
Combined
chronic
toxicity/
oncogenicity
feeding
–
Rat
Guideline
#:
OPPTS
870.4300
[§
83
5]
MRID
No.:
41094101,
41853701
and
42891201
Executive
Summary:
Results
from
interim
sacrifice
of
15
rats/
sex/
group
at
30
days
and
26
weeks,
as
well
as,
15
rats/
sex/
group
at
52
weeks
and
final
results
of
an
ongoing
chronic/
oncogenicity
study
are
presented
in
this
report
(MRID
41094101,
41853701
and
42891201).
In
this
chronic
toxicity/
oncogenicity
study,
Lindane
(99.75%
a.
i.,
Lot
no.
DA433)
was
administered
in
the
diet
to
groups
of
115
male
and
115
female
Wistar
rats
at
concentrations
of
0,
1,
10,
100,
or
400
ppm
for
2
years.
Corresponding
delivered
doses
were
0,
0.
05,
0.47,
4.81,
and
19.66
mg/
kg/
day,
respectively,
for
males
and
0,
0.
06,
0.59,
6.00,
and
24.34
mg/
kg/
day,
respectively,
for
females.
No
clinical
signs
of
toxicity
were
observed
during
the
first
26
weeks;
however
by
52
weeks
convulsions
in
11
high
dose
females
were
observed.
No
other
clinical
signs
were
observed.
Survival
at
the
end
of
the
study
was
36,
36,
31,
20,
and
16%
for
males
and
49,
38,
44,
35,
and
18%
for
females
in
the
0,
1,
10,
100,
and
400
ppmgroups,
respectively.
Survival
of
highdose
males
was
similar
to
the
controls
through
week
93.
For
females,
however,
survival
was
significantly
decreased
in
the
high
dose
group
with
50%
survival
reached
at
week
89
compared
to
week
104
for
the
control
group.
Body
weights
were
slightly
less
than
the
controls
for
the
high
dose
males
(
6%)
and
females
(
8%)
during
weeks
1
5
of
the
study,
but
gradually
increased
to
within
2%
of
the
control
level
by
week
26
for
males
and
week
9
10
for
females.
Because
final
body
weights
of
the
100
ppm
males
were
similar
to
the
controls,
the
init
ial
reduction
in
weight
gain
was
not
considered
biologically
significant.
Final
body
weights
of
the
high
dose
males
were
significantly
(
14%;
p
<
0.
05)
less
than
the
controls.
Body
weights
and
body
weight
gains
for
the
treated
females
were
similar
to
the
controls
throughout
the
study.
Food
consumption
by
t
he
high
dose
groups
was
decreased
15%
in
males
and
19%
in
females
during
the
first
week
of
the
study,
however,
total
food
consumption
for
the
entire
study
was
similar
to
the
control
levels.
Platelet
counts
were
significantly
(p
<
0.05
or
0.01)
increased
(20%
or
less)
in
the
100
and
6
400
ppm
males
at
week
12
and
in
100
and
400
ppm
males
and
females
at
week
24,
but
not
at
later
time
points.
High
dose
males
and
females
had
significant
(p
<
0.05
or
0.01)
decreases
in
red
blood
cell
parameters
at
week
104
as
compared
with
the
controls:
hemoglobin
was
15.6
and
17.6%,
respectively,
erythrocyte
counts
were
14.1%
and
21%,
respectively,
and
PCV
was
15.9%
and
18.2%,
respectively.
Significant
(p
<
0.05
or
0.01)
changes
in
clinical
chemistry
parameters
were
observed
in
highdose
males
and
females
during
the
first
year
of
the
study.
Inorganic
phosphorous
was
increased
by
7.3
38.5%
and
calcium
was
increased
by
3.4
10%
in
males
and
females;
cholesterol
was
increased
by
45
110%
and
urea
was
increased
by
20
54%
in
females;
and
the
albumin/
globulin
ratio
was
decreased
by
8.
3
18.
2%
in
females.
All
parameters
were
similar
to
the
control
levels
by
week
104.
High
dose
males
and
females
had
increased
absolute
and
relative
liver
weights
at
all
interim
sacrifices,
although
statistical
significance
was
not
always
reached.
At
study
termination,
absolute
and
relative
liver
weights
were
significantly
(p
<
0.01)
increased
by
21.
2%
and
38.5%,
respectively,
in
high
dose
males
and
by
31.6%
and
33.5%,
respectively,
in
high
dose
females.
At
100
ppm,
absolute
liver
weights
were
increased
by
8.6
11.2%
(n.
s.)
and
relative
liver
weights
were
increased
by
14.4
17.6%
(p
<
0.05
or
0.01)
for
both
sexes
at
week
104.
Significant
(p
<
0.05
or
0.01)
increases
in
absolute
and
relative
spleen
weights
at
week
52
and
in
relative
spleen
weights
at
week
104
were
also
noted,
but
the
sex
was
not
identified.
The
incidence
rate
of
periacinar
hepatocytic
hypertrophy
was
significantly
increased
in
the
100
and
400
ppmgroups
with
25/
50
males
and
19/
50
females
affected
at
100
ppmand
40/
50
males
and
43/
50
females
affected
at
400
ppm.
No
treatment
related
histopathological
lesions
were
observed
in
the
spleen
or
bone
marrow.
Kidney
lesions
in
males
indicative
of
alpha
2
globulin
accumulation
were
observed
in
animals
treated
with
10
ppm.
Therefore,
the
systemic
toxicity
LOAEL
for
male
and
female
rats
is
100
ppm
(4.
81
and
6.0
mg/
kg/
day,
respectively)
based
on
periacinar
hepatocyte
hypertrophy,
increased
liver
and
spleen
weights,
and
decreased
platelets.
The
systemic
toxicity
NOAEL
is
10
ppm
(0.
47
and
0.59
mg/
kg/
day
for
males
and
females,
respectively).
Eight
additional
males
were
identified
as
having
adrenal
pheochromocytomas.
The
revised
percentages
of
animals
with
adrenal
tumors
in
the
0,
1,
10,
100,
and
400
ppm
groups
are
14,
16,
16,
6,
and
24%
for
benign
tumors,
respectively,
and
0,
0,
6,
8,
and
2%
for
malignant
tumors,
respectively.
Statistical
significance
was
not
reached
by
relevant
tests.
For
comparison,
historical
control
data
fromCharles
River
and
publications
in
the
open
literature
were
submitted.
The
10
and
100
ppm
groups
had
malignant
tumor
incidence
rates
greater
than
the
historical
control
rate
(0
2%).
The
high
dose
group
also
had
a
slight
excess
of
benign
and
combined
tumor
rates
as
compared
with
the
historical
control
rates
(8
22%
benign,
combined
could
not
be
calculated),
but
this
same
net
tumor
incidence
was
the
same
as
the
control
group
of
a
published
study.
In
the
current
study,
pheochromocytomas
were
not
considered
the
cause
of
death
for
any
animal
with
the
exception
of
a
single
animal
in
the
7
Chronic
RfD
=
NOAEL
(mg/
kg/
day)
=0.
47=
0.0047
mg/
kg/
day
UF
100
100
ppm
group.
Therefore,
no
evidence
of
dose
related
and
statistically
significant
increase
in
adrenal
tumors
was
observed
in
this
study.
The
study
was
conducted
at
adequate
dose
levels.
Dose
and
Endpoint
for
Establishing
a
Chronic
RfD:
The
NOAEL
is
0.47
mg/
kg/
day
based
on
periacinar
hepatocyte
hypertrophy,
increased
liver
and
spleen
weights,
and
decreased
platelets
in
male
rats
Uncertainty
Factor(
s):
100;
10X
intraspecies
variations
and
10X
interspecies
extrapolation
Comments
about
Study/
Endpoint/
Uncertainty
Factor(
s):
The
HIARC
concurred
with
the
TES
committee's
decision
(1994,
DOC
013460)
that
the
toxicological
endpoint
of
concern
was
the
periacinar
hepatocyte
hypertrophy
and
not
kidney
lesions
associated
with
alpha
2
globulin
which
is
thought
to
be
inappropriate
for
human
risk
assessment.
2.3
Occupational/
Residential
Exposure
2.3.1
Dermal
Absorption
Selected
Study:
Dermal
absorption
study
Guideline
#:
OPPTS
870.7600
[§
85
3]
MRID
No.:
40056107,
40056108
Executive
Summary:
In
a
dermal
absorption
study,
24
male
Crl:
CD
®
(SD)
BRrats
per
group
received
dermal
applications
of
Lindane
20%
emulsifiable
concentrate
([
14
C]
Lindane
and
unlabeled
Lindane)
at
doses
of
0.1,
1.0,
or
10
mg/
rat.
Four
animals/
group
were
bled
and
sacrificed
at
intervals
of
0.
5,
1,
2,
4,
10,
or
24
hours
after
application
of
the
test
article.
Quantities
absorbed
increased
with
dose
and
duration
of
exposure
while
percent
absorbed
increased
with
time
and
decreased
with
dose.
Percents
of
the
low,
mid,
and
high
doses
absorbed
were
0.
6,
0.
96,
and
0.
66%
after
0.
5
hours;
18.07,
8.31,
and
2.81%
after
10
hours;
and
then,
increased
to
27.72,
20.86,
and
5.
05%
after
24
hours.
The
total
amount
of
test
article
absorbed
after
24
hours,
as
calculated
from
urine,
feces,
and
carcass,
was
0.
028,
0.21,
and
0.
51
mg
for
the
low,
mid,
and
high
dose
groups,
respectively.
The
process
appears
to
be
approaching
saturation
at
the
high
dose.
Recovered
radioactivity
(absorbed,
skin,
skin
rinse,
filter
paper
and
spreader)
was
74.19,
70.19
and
58.35%
of
the
applied
dose
after
24
hours
of
exposure
in
the
8
low,
mid,
and
high
dose,
respectively.
This
study
is
considered
Acceptable/
guideline
and
satisfies
the
requirements
for
a
dermal
absorption
study
in
rats
[85
2].
Percent
Dermal
Absorption
by
Rats
Based
on
Exposure
and
Duration
Applied
dose/
rat
(mg/
kg)
Exposure
Duration
4
hr
10
hr
24
hours
0.1
mg
(.
25
mg/
kg)
10.1
18.1
27.7%
1.0
mg
(2.5
mg/
kg)
5.3
8.
3
20.9%
10.0
mg
(25
mg/
kg)
2.0
2.
8
5.0%
Executive
Summary:
In
a
dermal
absorption
study,
24
male
Hra:
(NZW)
SPF
rabbits
per
group
received
dermal
applications
of
Lindane
20%
emulsifiable
concentrate
([
14
C]
Lindane
and
unlabeled
Lindane)
at
doses
of
0.
5,
5.
0,
or
50
mg/
rabbit.
Four
animals/
group
were
bled
and
sacrificed
at
intervals
of
0.
5,
1,
2,
4,
10,
or
24
hours
after
application
of
the
test
article.
Quantities
absorbed
increased
with
dose
and
duration
of
exposure
while
percent
absorbed
increased
with
time
and
decreased
with
dose.
Percentages
of
the
low,
mid,
and
high
doses
absorbed
were
5.
97,
6.68,
and
1.
99%
after
0.
5
hours;
51.68,
23.76
and
10.96%
after
10
hours;
and
then
increased
to
55.68,
39.99,
and
16.56%
after
24
hours.
The
total
amount
of
test
article
absorbed
after
24
hours,
as
calculated
from
urine,
feces,
and
carcass,
was
0.
28,
2.00,
and
8.
46
mg
for
the
low
mid,
and
high
dose
groups,
respectively.
The
original
DER
states
that
No
evidence
of
saturation
of
the
absorption
process
was
observed;
however
upon
further
examination
it
appears
that
there
is
evidence
of
saturation
at
the
highest
dose
(50
mg/
rabbit)
tested.
Recovered
radioactivity
(absorbed,
skin,
skin
rinse,
filter
paper
and
spreader)
was
82.01,
78.27
and
66.34%
of
the
applied
dose
after
24
hours
of
exposure
in
the
low,
mid,
and
high
dose,
respectively.
This
study
is
considered
Acceptable/
guideline
and
satisfies
the
requirements
for
a
dermal
absorption
study
in
rabbits
[85
2].
At
10
hours,
18%
of
the
applied
material
is
absorbed.
IPCS
(1991)
sites
even
higher
percentages
at
24
hours,
ranging
from
28%
for
rat
and
17
to
56%
for
rabbit.
Percentage
(%)
Dermal
Absorption:
9
The
absorption
has
been
determined
to
be
10%.
Comments
about
Dermal
Absorption:
The
HIARC
concurred
with
the
TES
committee
decision
(HED
Doc.
#
013460)
that
the
dermal
absorption
factor
is
10%
based
on
a
published
report
by
Feldman
and
Maibach
(Toxicology
and
Applied
Pharmacology
28,
126
132,
1974).
The
Maibach
study
tested
12
pesticides
and
herbicides,
including
Lindane,
on
human
subjects
(6
per
chemical)
to
quantitate
their
dermal
penetration.
C
14
labeled
chemicals
were
applied
topically
(4
g/
cm
2
)
to
the
forearm
or
via
the
intravenous
route
(1
Ci).
Excretion
of
the
chemicals
was
then
monitored
by
collecting
and
analyzing
urine
samples
during
the
5
day
testing
period.
All
results
were
calculated
as
percent
of
the
injected
or
applied
dose.
Data
obtained
after
IV
dosing
was
used
to
correct
the
skin
penetration
data
for
incomplete
urinary
recovery.
Lindane
was
shown
to
have
a
penetration
factor
of
9.3%
±
3.
7
(SD).
2.
3.
2
Short
term
Dermal
(1
7
days)
Exposure
Selected
Study:
Developmental
Neurotoxicity
Study
Guideline
#:
OPPTS
870.6200
[§
83
6]
MRID
No.:
45073501
Executive
Summary:
In
a
developmental
neurotoxicity
study
(MRID
45073501),
lindane
(Batch
No.
HLS
96/
1;
99.78%
a.
i.)
was
administered
to
presumed
pregnant
Hsd
Brl
Han:
Wist
(Han
Wistar)
rats
in
the
diet
at
concentrations
of
0,
10,
50,
or
120
ppm
from
gestation
day
(GD)
6
through
lactation
day
10.
These
concentrations
resulted
in
F0
maternal
doses
of
0.
8
0.
9,
4.
2
4.
6,
and
8.0
10.5
mg/
kg/
day,
respectively,
during
gestation
and
1.
2
1.
7,
5.
6
8.
3,
and
13.7
19.1
mg/
kg/
day,
respectively,
during
lactation.
The
developmental
neurotoxicity
of
lindane
was
evaluated
in
the
F1
offspring.
F1
animals
(10/
sex)
were
evaluated
for
FOB,
motor
activity,
auditory
startle
response,
and
learning
and
memory
as
well
as
developmental
landmarks
such
as
vaginal
perforation
and
balanopreputial
separation,
and
brain
weights
and
histopathology
on
days
11
and
65,
including
morphometrics.
Small
differences
in
absolute
maternal
body
weights
(7
8%)
were
observed
between
the
high
dose
and
control
groups
during
gestation
and
early
lactation
(through
day
11).
Body
weight
gains
by
the
high
dose
dams
from
GD
6
through
GD
20
were
64
79%
(p
0.01)
of
the
control
level.
Body
weight
changes
during
lactation
were
similar
between
the
treated
and
control
groups.
During
gestation,
food
consumption
by
the
high
dose
group
was
significantly
(p
0.01;
74
92%
of
controls)
less
than
the
control
group
for
the
intervals
of
GD
10
13,
14
17,
and
18
10
19.
Food
consumption
by
the
low
and
mid
dose
groups
during
gestation
and
by
all
treated
groups
during
lactation
was
similar
to
the
controls.
Absolute
body
weights
of
the
treated
male
and
female
pups
in
mid
and
high
dose
groups
during
lactation
were
12
18%
and
16
20%
less
than
controls,
respectively
on
days
4
11
of
lactation
with
recovery
to
less
than
10%
by
day
21.
Body
weight
gains
(p
0.05
or
0.01)
on
lactation
days
1
4
and
1
11
were
76%
and
84%,
respectively,
of
the
control
levels
for
mid
dose
males,
79%
and
79%,
respectively,
for
mid
dose
females,
60%
and
73%,
respectively
for
high
dose
males,
and
63
and
75%,
respectively,
for
high
dose
females.
Body
weight
gains
by
all
treated
groups
were
similar
to
the
controls
during
lactation
days
11
21.
Except
for
mid
and
high
dose
females,
postweaning,
body
weight
gains
were
similar
between
the
treated
and
control
groups.
Body
weight
differences
for
high
dose
dams
were
10%
less
at
the
beginning
of
lactation
and
recovered
to
6%
less
by
the
end
of
the
study.
The
high
dose
group
had
a
greater
number
of
stillborn
pups
as
indicated
by
a
live
birth
index
of
77%
compared
with
99%
for
the
control
group.
In
addition,
nine
highdose
litters
either
died
or
were
sacrificed
moribund
on
lactation
days
1
4.
This
resulted
in
a
viability
index
for
the
high
dose
group
of
71%
compared
with
89%
for
the
controls.
Pup
mortality
in
the
mid
and
high
dose
groups
in
litters
surviving
to
weaning
was
greater
before
day
4
than
in
controls
[
3
pups
in
2/
20
controls;
18
pups
in
8/
22
litters,
mid
dose;
14
pups
in
4/
15
litters,
high
dose].
Survival
was
not
affected
at
any
time
in
the
low
dose
group
as
compared
with
the
control
group.
No
dose
or
treatment
related
differences
were
observed
between
treated
and
control
groups
for
duration
of
gestation,
number
of
pups/
litter
on
day
1,
or
per
cent
male
offspring.
At
necropsy,
no
treatment
related
gross
abnormalities
were
observed
in
the
dams
or
offspring.
Absolute
and
relative
liver
and
kidney
weights
of
the
offspring
were
not
affected
by
treatment.
A
few
clinical
signs
were
observed
in
high
dose
dams
and
pups;
increased
reactivity
to
handling
in
dams
on
weeks
2
and
3
of
dosing,
and
slower
surface
righting
in
pups
on
day
4.
There
were
no
effects
on
measures
of
physical
or
sexual
development.
There
was
an
increase
in
motor
activity
at
the
mid
and
high
dose
during
lactation
in
both
sexes.
Some
decrease
in
habituation
of
motor
activity
in
females
on
day
22
was
also
seen.
While
there
was
no
effect
on
auditory
startle
reflex
amplitudes,
there
was
a
clear
reduction
in
auditory
startle
response
habituation
in
both
sexes
at
the
high
dose
on
day
28
and
on
day
60.
Slight
decreases
in
absolute,
but
not
relative,
brain
weights
in
mid
and
high
dose
female
pups
were
observed
on
postnatal
day
11
(9
10%)
but
narrowed
to
3
5%
less
by
day
65.
Brain
lengths
and
widths
were
similar
between
the
treated
and
control
pups.
Morphometric
brain
measurements
did
not
show
any
significant
differences
in
the
sizes
of
the
neocortex,
hippocampus,
corpus
callosum,
or
cerebellum
on
days
11
or
65.
There
were
no
effects
on
histopathology
of
the
nervous
system.
The
maternal
toxicity
LOAEL
is
120
ppm
(13.7
mg/
kg/
day)
based
on
decreased
body
weight
gains,
decreased
food
consumption,
and
increased
reactivity
to
handling.
The
maternal
toxicity
NOAEL
is
50
ppm
(5.
6
mg/
kg/
day).
11
The
developmental
toxicity
LOAEL
is
50
ppm
(5.
6
mg/
kg/
day)
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
The
developmental
toxicity
NOAEL
is
10
ppm
(1.
2
mg/
kg/
day).
This
study
is
classified
as
Unacceptable/
Guideline
[870.6300
(§
83
6)]
since
laboratory
validation
studies
of
the
neurobehavioral
tests
were
not
included,
but
it
may
be
upgraded
and
found
acceptable
if
this
information
is
obtained.
The
number
of
animals
tested
at
the
highest
dose
is
only
6
compared
to
the
required
number
of
10
animals
per
dose.
Dose
and
Endpoint
for
Risk
Assessment:
The
NOAEL
is
1.2
mg/
kg
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
Comments
about
Study/
Endpoint/
Uncertainty
Factor(
s):
A
90
day
dermal
toxicity
study
in
rabbits
was
available;
the
NOAEL
was
10
mg/
kg/
day
and
the
LOAEL
was
60
mg/
kg/
day
based
on
hepatic
toxicity.
The
HIARC
did
not
consider
this
study
to
be
appropriate
for
risk
assessment
and
instead
selected
an
oral
endpoint
due
to:
1)
the
concern
for
developmental
effects
as
seen
in
pups
in
the
developmental
neurotoxicity
study
2)
developmental
effects
are
not
evaluated
in
the
dermal
toxicity
study
3)
the
dermal
toxicity
study
was
conducted
in
the
rabbit,
while
the
increased
susceptibility
was
seen
in
rat
pups
via
an
oral
route
4)
this
endpoint
will
be
protective
of
dermally
exposed
workers
Since
an
oral
endpoint
was
selected,
a
10%
dermal
absorption
factor
should
be
used
for
route
to
route
extrapolation.
Although
this
study
is
classified
as
unacceptable/
guideline,
it
is
adequate
for
endpoint
selection
because
the
deficiencies
are
related
to
submission
of
additional
data
and
not
the
quality
of
the
study.
2.3.3
Intermediate
term
Dermal
(1
Week
to
Several
Months)
Selected
Study:
Developmental
Neurotoxicity
Study
in
rats
Dose
and
Endpoint
for
Risk
Assessment:
The
NOAEL
is
1.2
mg/
kg
based
on
reduced
pup
survival,
decreased
body
weights
and
bodyweight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
Comments
about
Study/
Endpoint:
See
Short
term
Dermal
Section
2.
3.
2
12
2.3.4
Long
term
Dermal
(Several
Months
to
Lifetime)
Selected
Study:
Chronic
toxicity
and
Oncogenicity
Study
in
rats
MRID
No.:
41094101,
41853701
and
42891201
Dose
and
Endpoint:
The
NOAEL
is
0.47
mg/
kg/
day
based
on
periacinar
hepatocyte
hypertrophy,
increased
liver
and
spleen
weights,
and
decreased
platelets
in
male
rats
Comments
about
Study/
Endpoint:
This
dose
and
endpoint
was
used
to
derive
the
chronic
RfD.
Since
an
oral
NOAEL
was
selected,
a
10%
dermal
absorption
factor
should
be
used.
2.
4
Inhalation
Exposure
(All
Durations)
Short
term
(1
7
days):
Selected
Study:
Subchronic
Inhalation
Toxicity
Study
Guideline
#:
OPPTS
870.3465
[§
82
4]
Accession
No.:
255003
Executive
Summary:
In
a
subchronic
inhalation
toxicity
study
(Accession
No.
255003),
Lindane
(99.9%
a.
i.,
Batch
no.
79044/
174)
was
administered
by
inhalation
to
groups
of
12
male
and
12
female
Wistar
rats
at
nominal
concentrations
of
0,
0.02,
0.10,
0.50,
or
5.0
mg/
m
3
,
6
h/
day
for
90
days.
Additional
control
and
high
concentration
groups,
12
rats/
sex,
were
treated
for
90
days
and
allowed
to
recover
for
6
weeks
before
sacrifice.
Analytically
measured
atmospheric
concentrations
were
0,
0.02,
0.12,
0.60,
and
4.
54
mg/
m
3
,
respectively.
The
arithmetic
mean
particle
size
of
the
aerosol
was
1.
11±
0.39
µm
and
the
geometric
mean
was
1.
03±
1.45
µm.
Lindane
was
detected
in
the
brain,
liver,
fat,
and
serum
of
all
exposed
rats.
The
chemical
accumulated
in
fat
with
levels
reaching
127,120
µg/
g
and
58,260
µg/
g
in
high
dose
females
and
males,
respectively.
After
the
recovery
period,
traces
of
lindane
were
still
detectable
in
the
tissues.
All
rats
survived
to
scheduled
sacrifice.
"Slight"
diarrhea
and
piloerection
were
observed
in
all
males
and
females
exposed
to
the
highest
concentration,
beginning
at
14
days
after
exposure
and
continuing
for
20
days.
No
exposure
related
effects
were
noted
for
body
weight
gain,
food
consumption,
water
consumption,
or
urinalysis
parameters.
Although
hematologyparameters
did
appear
to
be
affected
bytreatment,
no
individual
animal
data
were
included
and
the
statistics
could
not
be
verified.
Clinical
chemistry
results,
especially
for
Na
+
,
K
+
,andCa
++
,
were
highly
variable.
Cytochrome
p
450
in
males
and
females
exposed
to
5
13
mg/
m
3
was
338%
and
174%,
respectively,
of
the
control
values
after
90
days,
but
similar
to
the
control
levels
after
the
recovery
period.
Bone
marrow
myelograms
from
animals
exposed
to
5
mg/
m
3
showed
significantly
(p
0.05)
increased
reticulocytes
(+
108%),
stem
cells
(+
31%),
and
myeloblasts
(+
33%)
in
males,
and
increased
reticulocytes
(+
55)
in
females,
and
decreased
(
45%)
lymphocytes
in
females.
However,
these
changes
in
bone
marrow
cannot
be
definitively
attributed
to
treatment
since
bone
marrow
from
the
other
exposed
groups
was
not
assayed.
Males
exposed
to
5
mg/
m
3
had
significantly
(p
0.05
or
0.01)
increased
absolute
(+
7.8%
to
+11.7%)
and
relative
(+
19.1%
to
19.2%)
kidney
weights
as
compared
with
the
controls.
Absolute
and
relative
kidney
weights
in
the
males
exposed
to
0.
5
mg/
m
3
were
increased
by
8
9.8%
and
6.
9
8.
2%,
respectively.
Although
not
statistically
significant,
the
increases
in
kidney
weights
for
these
groups
were
considered
biologically
significant.
After
the
recovery
phase,
kidney
weights
from
the
exposed
males
were
similar
to
the
controls.
In
females
exposed
to
5
mg/
m
3
absolute
and
relative
kidney
weights
were
increased
(p
0.05)
by
9.2
9.9%
and
7.
9
8.
2%,
respectively,
as
compared
with
the
controls.
In
high
dose
males,
absolute
liver
weights
were
not
affected,
but
relative
liver
weights
were
slightly
(6.
9%)
higher
than
the
controls.
For
females
exposed
to
the
highest
dose,
absolute
and
relative
liver
weights
were
12.2%
and
11.0%
higher,
respectively,
than
the
controls.
No
differences
in
absolute
and
relative
liver
weights
were
noted
between
the
exposed
and
control
groups
after
the
recovery
period.
Kidney
lesions
in
males
exposed
to
0,
0.
02,
0.10,
0.50,
or
5.0
mg/
m
3
,
were
observed
in
17%,
0,
25%,
83%
and
82%,
respectively,
of
the
animals.
These
lesions
included
cloudy
swelling
of
the
tubule
epithelia,
dilated
renal
tubules
with
protein
containing
contents,
and
proliferated
tubules.
After
the
recovery
phase,
only
cloudy
swelling
of
the
tubule
epithelia
was
observed
in
two
control
animals
and
one
high
concentration
animal.
These
effects
are
consistent
with
the
accumulation
of
alpha
2
globulin
and
is
not
relevant
for
human
risk
assessment.
Therefore,
the
systemic
toxicity
LOAEL
is
5.0
mg/
m
3
based
on
increased
kidney
weights
of
female
rats
and
bone
marrow
effects.
The
systemic
toxicity
NOAEL
is
0.5
mg/
m
3
.
This
study
is
considered
Acceptable/
guideline
and
satisfies
the
requirement
for
a
subchronic
inhalation
toxicity
study
in
rats
[82
4].
It
should
be
noted
that
several
translation
errors
were
found
and
corrected
by
referring
to
the
original
text.
Individual
animal
data
were
not
available
for
statistical
analysis
of
blood
elements
or
clinical
chemistry
data.
Dose
and
Endpoint
for
Risk
Assessment:
The
NOAEL
is
0.5
mg/
m
3
(0.
13
mg/
kg)
based
on
clinical
signs
(diarrhea
and
piloerection)
seen
at
day
14
after
exposure
and
continuing
for
20
days.
14
Comments
about
Study/
Endpoint:
The
HIARC
established
a
NOAEL
of
0.5
mg/
m
3
for
this
risk
assessment
based
on
clinical
signs
seen
at
the
highest
concentration
tested
(5
mg/
m
3
).
This
NOAEL
is
applicable
and
appropriate
only
for
short
termexposure
risk
assessment
because
the
effects
were
seen
during
this
period
of
exposure.
The
Committee
further
noted
that
this
dose
would
be
protective
against
developmental
effects.
Intermediate
term
(7
days
to
several
months):
Selected
Study:
Subchronic
Inhalation
Toxicity
Study
Accession
No.:
255003
Dose
and
Endpoint
for
Risk
Assessment:
The
NOAEL
is
0.5
mg/
m
3
(0.
13
mg/
kg)
based
on
increased
kidney
weights
in
females
and
bone
marrow
effects
(increased
reticulocytes,
increased
myelocytes,
decreased
lymphocytes)
at
5
mg/
m
3
.
Comments
about
Study/
Endpoint:
The
NOAEL
of
0.1
mg/
m
3
based
on
kidney
lesions
and
increased
kidney
weights
in
male
rats
at
0.5
mg/
m
3
,
selected
previously
on
June
13
th
,
2001
HIARC
meeting,
has
been
changed.
The
change
in
endpoint
selection
was
necessary
because
the
kidney
effects
are
due
to
the
accumulation
of
alpha
2
globulin,
a
low
molecular
weight
protein
in
the
male
rat
kidney,
and
this
accumulation
initiates
a
sequences
of
events
that
may
lead
to
tumor
formation.
This
phenomenon
does
not
occur
in
female
rats.
The
Agency
has
determined
that
in
this
special
situation,
the
male
rat
is
not
a
good
model
for
assessing
human
risk
(USEPA,
1991).
The
route
and
duration
of
exposure
in
this
study
is
appropriate
for
this
exposure
scenario.
Long
Term
Inhalation:
Based
on
the
use
pattern
(maximum
of
60
days),
no
long
term
inhalation
exposure
is
expected.
If
there
is
a
change
in
the
use
pattern
and
a
long
term
exposure
becomes
likely,
then
the
inhalation
NOAEL
of
0.
5
mg/
m
3
(0.
13
mg/
kg)
should
be
used
for
risk
assessment.
Recommendation
for
Aggregate
Exposure
Risk
Assessments
There
are
no
registered
residential
uses
at
this
present
time;
therefore,
non
occupational
aggregate
exposure
risk
assessment
will
be
limited
to
food
and
water.
For
occupational
risks,
separate
assessments
should
be
conducted
for
dermal
and
inhalation
exposures
because
the
effects
selected
for
assessment
of
dermal
risk
do
not
share
a
common
toxicity
with
the
effects
selected
for
inhalation
risk.
15
Margins
of
Exposures
for
Occupational/
Residential
Exposure
Risk
Assessments
An
MOE
of
100
is
adequate
for
both
dermal
and
inhalation
occupational
exposure
at
all
time
durations.
III.
CLASSIFICATION
OF
CARCINOGENIC
POTENTIAL
3.1
Combined
Chronic
Toxicity/
Carcinogenicity
Study
in
Rats
MRID
No.:
41094101,
41853701
and
42891201
Executive
Summary:
See
Chronic
RfD
section
Discussion
of
Tumor
Data:
No
tumors
were
noted
in
this
study.
The
findings
included
a
significant
increase
in
the
incidence
rate
of
periacinar
hepatocytic
hypertrophy
in
the
100
and
400
ppm
groups
with
25/
50
males
and
19/
50
females
affected
at
100
ppm
and
40/
50
males
and
43/
50
females
affected
at
400
ppm.
No
treatment
related
histopathological
lesions
were
observed
in
the
spleen
or
bone
marrow.
For
further
details,
please
refer
to
the
chronic
RfD
section
2.2.
Adequacy
of
the
Dose
Levels
Tested:
The
dose
levels
are
adequate
to
assess
the
carcinogenic
potential
of
Lindane.
3.2
Carcinogenicity
Study
in
Mice
NO
ACCEPTABLE
STUDY
IS
AVAILABLE
Comments
and
Discussion:
A
new
mouse
carcinogenicity
study
is
expected
in
December
2000
3.3
Classification
of
Carcinogenic
Potential
A
new
Cancer
Assessment
Review
Committee
(CARC)
meeting
will
review
the
recently
submitted
mouse
carcinogenicity
study
and
establish
a
new
classification
for
lindane,
if
applicable.
According
to
the
TES
committee
report
(1994,
Doc
013460),
Lindane
has
not
been
classified
by
the
HED
Cancer
Peer
Review
Committee.
It
was
determined
by
the
RfD/
Peer
Review
Committee
(8/
25/
93)
that:
"The
mouse
carcinogenicity
data
were
considered
insufficient
because
of
major
deficiencies
associated
with
all
studies
available."
Lindane
however
had
been
previously
classified
by
the
Cancer
Assessment
Group
of
the
Office
of
Research
and
Development
(memorandum
dated
7/
23/
85
from
R.
E.
McGaughy
to
Anne
Barton)
as
a
group
B2/
C
carcinogen
based
on
increased
incidence
of
mouse
liver
tumors.
The
upper
bound
slope
of
the
dose
response
was
given
in
that
memorandum
as
Q1*
=
1.1
(mg/
kg/
day)
1
.
16
IV.
MUTAGENICITY
Executive
Summary:
In
a
mammalian
cell
gene
mutation
assay
(MRID
00144500)
conducted
in
Chinese
hamster
V79
cells,
lindane
was
tested
in
the
absence
of
metabolic
activation
at
dose
levels
of
2.
5,
5,
10,
25,
50,
70,
100,
and
150
µg/
ml
and
in
the
presence
of
metabolic
activation
at
dose
levels
of
5,
10,
25,
50,
100
250
and
500
µg/
ml.
The
S9
fraction
used
for
metabolic
activation
was
obtained
from
Aroclor
1254
induced
mouse
liver.
Tests
with
and
without
activation
were
conducted
under
aerobic
and
anaerobic
conditions.
Under
anaerobic
conditions,
lindane
without
S9
was
cytotoxic
to
the
V79
cells
at
dose
levels
above
10
µg/
ml
and
with
S9
at
dose
levels
above
150
µ
g/
ml.
No
mutagenic
activity
of
lindane
was
observed
in
V79
cells
under
any
combination
of
conditions
up
to
cytotoxic
doses.
No
statistical
analysis
was
performed;
solvent
control
values
were
somewhat
variable;
the
positive
control
values
were
appropriate
for
the
experiments
under
aerobic
conditions,
but
the
positive
control
employed
for
anaerobic
conditions
did
not
exhibit
an
increase
in
anaerobic
mutation
frequency
compared
to
aerobic
mutation
frequency.
Moreover,
there
was
no
experimental
verification
that
anaerobic
conditions
were
either
established
before
exposure
to
lindane
or
maintained
throughout
the
exposure
period.
Since
the
anaerobic
positive
control
did
not
produce
more
mutations
under
anaerobic
than
under
aerobic
conditions,
anaerobic
metabolic
pathways
may
not
have
been
induced
in
the
cells.
This
study
is
classified
as
Unacceptable/
Guideline
and
does
not
satisfy
guideline
requirements
for
a
mammalian
cell
culture
gene
mutation
assay
in
V79
cells
(84
2)
because
of
the
deficiencies
described
above.
This
classification
could
not
be
upgraded
without
repeating
the
experiments.
Executive
Summary:
In
a
mammalian
in
vivo
sister
chromatid
exchange
(SCE)
assay
(MRID
00024504),
50µg
tablets
of
bromodeoxy
uridine
were
implanted
into
male
and
female
CF
1
mice.
Two
hours
after
implantation,
lindane
was
administered
ip
in
arachis
oil
at
dose
levels
of
1.3,
6.4
and
32.1
mg/
kg.
These
doses
were
reported
to
be
1/
75,
1/
15
and
1/
3
of
the
LD50
.
The
vehicle
control
group
received
arachis
oil
and
the
positive
control
group
received
10
mg/
kg
of
cyclophosphamide
in
saline.
Colcemid
was
administered
22
hours
later
to
arrest
cells
in
mitosis,
and
after
another
2
hours
the
animals
were
sacrificed.
For
each
dose
level
and
control
group,
30
bone
marrow
cells
from
each
of
5
animals
of
each
sex
were
examined
for
SCEs.
No
toxicity
was
reported
in
any
treatment
group.
Slight
but
significant
increases
in
SCEs
over
the
vehicle
controls
were
observed
in
female
but
not
in
male
animals
at
all
dose
levels
tested
but
were
not
dose
related
(1.29
[sic],
1.82,
and
2.
12
SCE/
cell).
Vehicle
control
17
values
for
female
animals
were
also
found
to
be
significantly
lower
than
those
for
males
(1.
56
±
0.089
SCE/
cell
compared
to
1.
86
±
0.207
SCE/
cell).
When
results
for
male
and
female
animals
were
pooled,
only
the
highest
dose
produced
a
significant
increase
in
SCEs
over
the
controls.
Positive
control
values
were
appropriate.
The
study
authors
concluded
that
no
chromosome
damage
was
observed
in
this
test.
This
study
was
classified
as
Acceptable/
Guideline
and
satisfies
the
guideline
requirements
for
a
sister
chromatid
exchange
study
in
mice
(in
vivo
SCE)
(84
2).
Executive
Summary:
In
a
mammalian
dominant
lethal
assay
(MRID
00062657),
10
male
Sprague
Dawley
rats
of
unspecified
age
per
group
were
exposed
to
lindane
administered
by
subcutaneous
injection
in
corn
oil
at
doses
of
0,
1,
3,
and
10
mg/
kg
five
time
per
week
for
10
weeks.
Immediately
following
treatment,
each
male
was
housed
with
two
virgin
females.
After
one
week,
the
females
were
replaced
with
two
more
virgin
females.
No
positive
control
group
was
included
in
the
study.
Females
were
sacrificed
14
days
after
evidence
of
mating
or,
lacking
evidence,
14
days
after
removal
from
males.
Uteri
were
examined
for
live
and
dead
implants
and
abnormalities.
Males
were
also
sacrificed
and
gross
pathological
analysis
performed.
Very
slight
but
not
statistically
significant
weight
loss
was
observed
in
the
male
animals
at
the
two
higher
doses.
No
mortality
or
treatment
related
clinical
signs
of
toxicity
were
noted.
No
treatment
related
effect
on
pregnancy
rate
was
observed,
although
pregnancy
rates
in
all
groups
were
low
during
the
first
week.
The
incidence
of
dead
implants
was
significantly
increased
at
the
lowest
dose
but
not
at
the
two
higher
doses
in
the
first
week
of
mating
but
this
increase
was
not
observed
during
the
second
week.
The
authors
conclude
that
lindane
did
not
cause
an
increase
in
the
incidence
of
dominant
lethals
in
this
study.
This
study
is
classified
as
Unacceptable/
Guideline
and
does
not
satisfy
the
guideline
requirements
for
a
dominant
lethal
test
in
the
rodent
(84
2)
because
no
positive
control
was
done,
the
criteria
for
toxicity
were
inadequate,
animal
age
was
not
given,
and
insufficient
numbers
of
pregnant
dams
were
produced
for
meaningful
evaluation.
Moreover,
no
rationale
was
provided
for
the
dose
selection,
unusual
route
of
administration
or
dosing
regime.
This
classification
could
not
be
upgraded
without
repeating
the
study.
IPCS
has
also
determined
that
Lindane
does
not
appear
to
have
mutagenic
potential.
18
V.
FQPA
CONSIDERATIONS
5.1
Adequacy
of
the
Data
Base
Acute
delayed
neurotoxicity
study
in
hen
(if
applicable)
X
Acute
and
subchronic
neurotoxicity
studies
(if
applicable)
X
Developmental
toxicity
studies
in
Rat
&
Rabbits
X
Two
Generation
Reproduction
Study
X
Developmental
neurotoxicity
study
(if
applicable)
THESE
STUDIES
ARE
AVAILABLE
AND
THE
DATA
BASE
IS
ADEQUATE
FOR
FQPA
EVALUATION
OF
FQPA.
5.
2
Neurotoxicity
Data
1
Acute
Neurotoxicity
§
81
7:
See
Acute
RfD
section
2
Subchronic
Neurotoxicity
§82
5
MRID:
44781101
Executive
Summary:
In
a
subchronic
oral
neurotoxicity
study
(MRID
44781101),
groups
of
10
Crl:
CD®
BR
rats/
sex/
group
were
administered
Lindane
(Batch
No.
HLS96/
1,
Purity
99.78%)
in
the
diet
for
13
weeks
at
concentrations
of
0
(control),
20,
100,
or
500
ppm.
Due
to
severe
toxic
reactions
to
treatment
at
500
ppm,
the
dose
was
reduced
to
400
ppm
on
day
11
of
treatment
thereafter.
These
doses
resulted
in
average
daily
intake
values
of
0,
1.4,
7.1,
and
28.1
mg/
kg/
day
for
males
and
0,
1.6,
7.9,
and
30.2
mg/
kg/
day
in
females
for
0,
20,
100,
and
500/
400
ppm,
respectively.
Functional
observational
battery
(FOB)
and
motor
activity
(MA)
tests
were
performed
prior
to
administration
and
after
4,
8,
and
13
weeks
of
treatment.
Body
weights
were
recorded
pre
test,
weekly
during
the
study
period
and
on
FOB
assessment
days.
Clinical
signs
were
recorded
at
least
once
daily.
At
study
termination
all
animals
were
sacrificed
and
fixed
by
whole
body
perfusion
and
designated
tissues
of
the
nervous
system
were
processed
for
microscopic
neuropathological
evaluation.
Three
females
in
the
500/
400
group
died
prior
to
scheduled
termination.
These
deaths
were
attributed
to
treatment
with
Lindane.
One
death
was
recorded
on
Day
11
of
the
study,
one
during
week
10
and
one
during
week
13.
Clinical
signs
prior
to
death
included
weight
loss,
swollen
muzzle
with
scabbing,
hunched
posture,
piloerection,
and
staining
of
the
anogenital
region.
Observations
in
surviving
females
treated
at
500/
400
ppm
were
hypersensitivity
to
touch,
staining
of
the
urogenital
region,
and
scabbing
of
the
toes.
Significant
treatment
related
decreases
(p<
0.05
or
p<
0.01)
in
body
weight
were
observed
19
among
males
and
females
treated
with
500/
400
ppm
of
14%
and
23%,
respectively.
Decreases
in
body
weight
gains
(70%
and
180%
,
p<
0.01),
food
consumption
(35%
and
50%
,
p<
0.05
or
p<
0.01,
respectively),
and
food
conversion
ratios
were
observed
for
males
and
females
in
the
500
ppm
groups
compared
to
the
control
group
for
the
first
week
of
the
study.
Male
rats
tended
to
recover
from
these
effects
after
the
dose
was
lowered.
Females,
however,
did
not
exhibit
this
same
level
of
recovery
as
their
food
consumption
remained
slightly
depressed
throughout
the
remainder
of
the
study.
Females
in
the
100
ppm
group
had
significantly
decreased
body
weight
gains
(40%,
p<
0.05)
compared
to
the
control
group
during
the
first
week
of
the
study
and
this
effect
continued,
although
not
at
a
level
of
significance
throughout
the
remainder
of
the
study.
Females
in
the
100
ppm
group
had
significantly
decreased
food
consumption
(16%,
p<
0.01)
for
the
first
week
of
the
study
and
this
trend
continued
throughout
the
study.
Liver
weights
were
also
found
to
be
increased
at
500/
400
ppm
for
both
sexes;
no
additional
information
was
given.
During
the
FOB
assessment
(table
A
is
attached
at
the
end
of
this
document),
males
and
females
treated
at
the
highest
dose
(500/
400
ppm)
were
perceived
as
difficult
to
handle.
They
also
were
observed
to
have
piloerection
and
hunched
posture.
Females
in
the
highest
dose
group
had
missing
claws
(3),
tended
to
urinate
more
often
than
controls,
had
a
higher
incidence
of
grooming
behavior,
rearing,
motor
activity,
and
one
female
was
observed
to
convulse.
Females
across
the
dose
groups
were
observed
walking
on
tiptoes
(5
7)
and
these
incidences
were
significantly
increased
compared
to
the
control
(1)
for
the
highest
dose
group.
Females
(5)
in
the
100
ppm
group
also
had
increased
incidences
of
grooming
behavior
at
the
Week
4
evaluation
and
one
animal
in
this
group
was
extremely
difficult
to
handle.
The
assessments
of
forelimb
and
hindlimb
grip
strength
as
well
as
hindlimb
splay
revealed
no
differences
for
any
of
the
treated
groups
compared
to
the
control
groups.
Colburn
motor
activity
was
also
similar
among
treated
groups
compared
to
the
control
groups.
No
neuropathological
endpoints
attributable
to
Lindane
administration
were
observed
during
the
histological
examinations
of
the
peripheral
or
central
nervous
systems
of
these
animals
at
any
exposure
concentration.
The
NOAEL
for
systemic
toxicity
is
100
ppm
for
males
(7.
1
mg/
kg)
and
20
ppm
for
females
(1.6
mg/
kg).
Based
on
the
substance
related
effects
on
body
weight,
body
weight
gain,
food
consumption,
and
clinical
signs
of
toxicity
the
LOAEL
levels
for
systemic
toxicity
in
males
is
500/
400
ppm
(28.1
mg/
kg)
and
100
ppm
for
females
(7.
9
mg/
kg).
The
NOAEL
for
neurotoxic
effects
is
100
ppm
for
males
(7.
1
mg/
kg)
and
females
(7.
9
mg/
kg).
The
neurotoxicity
LOAEL
is
500/
400
ppm
based
on
hypersensitivity
to
20
touch
and
hunched
posture.
This
study
is
classified
Acceptable/
guideline
and
satisfies
the
Subdivision
F
guideline
requirement
for
an
acute
oral
neurotoxicity
study
(§
81
8)
in
rats.
5.3
Developmental
Toxicity
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
42808001),
20
presumed
pregnant
CFY
(derived
from
Charles
River
CD)
rats
per
group
were
administered
technical
Lindane
(purity
not
given;
Batch
No.
6801/
403)
by
gavage
in
0.5%
carboxymethylcellulose
at
doses
of
0,
5,
10,
and
20
mg/
kg/
day
on
gestation
days
(GD)
6
15,
inclusive.
On
GD
20,
dams
were
sacrificed
by
CO2
,
subjected
to
gross
necropsy,
and
all
fetuses
examined
externally.
Approximately
one
third
of
each
litter
was
processed
for
visceral
examination
and
the
remaining
two
thirds
was
processed
for
skeletal
examination.
Deaths
of
two
high
dose
dams
were
attributed
by
the
authors
to
treatment
although
the
cause
of
death
was
not
reported.
No
treatment
related
clinical
signs
of
toxicity
were
observed
in
any
animal.
Body
weight
gains
and
food
consumption
by
the
mid
and
highdose
groups
were
decreased
during
the
treatment
interval
as
compared
with
the
controls.
Body
weight
gains
by
the
mid
and
high
dose
dams
were
70%
and
46%,
respectively,
of
the
control
values
during
GD
6
14.
Food
consumption
by
the
mid
and
high
dose
groups
was
72%
of
the
control
level
during
GD
7
10
and
92%
and
65%,
respectively,
during
GD
11
14.
It
should
be
noted
that
data
were
not
available
for
the
entire
dosing
interval
and
that
statistical
analyses
were
not
provided
for
these
data.
Maternal
necropsy
was
unremarkable.
Organ
weights
were
similar
between
the
treated
and
control
groups.
Therefore,
the
maternal
toxicity
LOAEL
is
10
mg/
kg/
day
based
on
reduced
body
weight
gain
and
food
consumption.
The
maternal
toxicity
NOAEL
is
5
mg/
kg/
day.
No
significant
differences
were
observed
between
the
control
group
and
the
treated
groups
for
number
of
corpora
lutea,
number
of
implantation
sites,
live
fetuses/
dam,
pre
and
postimplantation
losses,
fetal
body
weights,
or
fetal
sex
ratios.
No
treatment
related
effects
were
found
at
external
or
visceral
examination
of
the
fetuses.
The
percentage
of
litters
in
the
control,
low,
mid,
and
high
dose
groups
containing
fetuses
with
extra
(14th)
ribs
was
12.7,
21.0,
31.7,
and
40.6%
(p
0.05),
respectively.
The
total
incidences
of
litters
containing
fetuses
with
skeletal
variants
were
43.4,
52.7,
59.5,
and
68.0%
(p
0.01),
respectively.
Although
the
response
rates
in
the
high
dose
group
for
extra
ribs
and
total
variants
are
within
the
upper
limit
of
historical
control
data,
they
were
considered
treatment
related
due
to
the
dose
related
manner
of
increase.
21
Therefore,
the
developmental
toxicity
LOAEL
is
20
mg/
kg/
day
based
on
increases
in
extra
ribs
and
total
skeletal
variants;
a
trend
for
increases
in
these
endpoints
at
the
lower
doses
is
recognized.
The
developmental
toxicity
NOAEL
is
10
mg/
kg/
day.
This
study
is
classified
as
Acceptable/
nonguideline
and
does
satisfy
the
requirements
for
a
developmental
toxicity
study
(83
3a)
in
rats.
Several
deficiencies
were
noted
in
the
conduct
of
this
study:
percent
purity
of
the
test
article
was
not
given,
less
than
20
litters/
group
were
available,
dosing
solutions
were
not
analyzed
for
concentration,
stability,
or
homogeneity,
and
much
of
the
individual
animal
data
were
not
included.
This
study
was
conducted
prior
to
implementation
of
current
guidelines.
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
00062658),
groups
of
presumed
pregnant
Sprague
Dawley
rats
were
administered
Lindane
(purity
not
given;
Lot
No.
36346)
by
subcutaneous
injection
in
corn
oil
(1
ml/
kg)
at
doses
of
0,
5,
15,
or
30
mg/
kg/
day
on
gestation
days
(GD)
6
15,
inclusive.
On
GD
19,
dams
were
sacrificed
and
the
fetuses
removed.
Approximately
one
third
of
the
fetuses
from
each
litter
were
sectioned
and
examined
for
visceral
malformations/
variations.
The
remaining
two
thirds
of
each
litter
were
"examined
externally"
and
processed
and
examined
for
skeletal
malformations/
variations.
Two
high
dose
animals
died
prematurely.
Clinical
signs
of
toxicity,
including
tremors,
convulsions,
urine
stains,
excitability,
and
anorexia,
were
reported
for
one
high
dose
animal.
However,
it
was
not
possible
to
correlate
clinical
signs
with
death
since
individual
animal
data
were
not
included.
No
other
clinical
signs
of
toxicity
were
reported.
Body
weight
gains
by
the
mid
and
high
dose
dams
were
76%
and
23%,
respectively,
of
the
control
levels
during
the
treatment
interval
with
both
groups
attaining
statistical
significance
(p
<
0.05).
Overall
body
weight
gain
by
the
high
dose
group
was
69%
(p
0.
05)
of
the
controls.
Food
consumption
by
the
high
dose
group
was
47%
of
the
control
level
during
GD
6
11.
Body
weight
gains
by
the
low
dose
group
and
food
consumption
for
the
low
and
mid
dose
groups
were
similar
to
the
controls
throughout
the
study.
Gross
necropsy
data,
other
than
uterine
data,
for
the
dams
were
not
provided.
Therefore,
the
maternal
toxicity
LOAEL
is
15
mg/
kg/
day
based
on
decreased
body
weight
gain.
The
maternal
toxicity
NOAEL
is
5
mg/
kg/
day.
No
treatment
related
effects
were
observed
between
the
control
group
and
the
treated
groups
for
number
of
corpora
lutea,
number
of
implantation
sites,
live
fetuses/
dam,
preand
post
implantation
losses,
fetal
body
weights,
or
fetal
crown
rump
lengths.
No
treatment
related
visceral
or
skeletal
malformations/
variations
were
observed
in
any
of
the
fetuses.
Results
of
external
examination
were
not
reported.
22
Therefore,
the
developmental
toxicity
NOAEL
is
>30
mg/
kg/
day
and
the
developmental
toxicity
LOAEL
was
not
identified.
This
study
is
classified
as
Unacceptable/
nonguideline
and
does
not
satisfy
the
requirements
for
a
developmental
toxicity
study
(83
3a)
in
rats.
Several
deficiencies
were
noted
in
the
conduct
of
this
study:
the
subcutaneous
route
is
not
the
preferred
method
of
administration,
percent
purity
of
the
test
article
was
not
given,
dosing
solutions
were
not
analyzed
for
concentration,
stability,
or
homogeneity,
less
than
20
litters/
group
were
available
for
evaluation,
and
much
of
the
individual
maternal
and
fetal
data
were
not
included.
However,
this
study
may
be
used
as
supplemental
information.
This
study
was
classified
unacceptable;
however,
a
new
developmental
toxicity
study
in
rabbits
is
not
required
and
thought
to
not
be
beneficial
for
the
following
reasons:
1)
The
developmental
toxicity
study
in
rabbits
and
rats
using
a
subcutaneous
route
of
administration
shows
no
developmental
effects
at
the
maternally
toxic
dose.
2)
The
skeletal
effects
observed
in
the
developmental
toxicity
study
in
rats,
with
gavage
as
the
route
of
administration,
are
within
historical
controls.
3)
More
severe
maternal
effects
are
seen
in
the
rabbit
study
with
subcutaneous
administration.
4)
The
rat
appears
to
be
the
more
sensitive
species
for
developmental
effects.
5)
A
developmental
neurotoxicity
study
has
already
been
submitted.
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
42808002),
13
presumed
pregnant
New
Zealand
white
rabbits
per
group
were
administered
Lindane
(purity
not
given;
Batch
No.
6801/
403)
by
gavage
in
0.5%
carboxymethyl
cellulose
at
doses
of
0,
5,
10,
or
20
mg/
kg/
day
on
gestation
days
(GD)
6
18,
inclusive.
On
GD
29,
dams
were
sacrificed,
subjected
to
gross
necropsy,
and
all
fetuses
examined
for
visceral
and
skeletal
malformations/
variations.
Data
from
external
examination
of
the
fetuses
was
not
included.
All
does
survived
to
scheduled
sacrifice.
No
treatment
related
clinical
signs
of
toxicity
were
observed.
Maternal
body
weight
and
food
consumption
were
similar
between
the
treated
and
control
groups.
Gross
necropsy
was
unremarkable.
Organ
weights
were
similar
between
the
treated
and
control
groups.
Therefore,
the
maternal
toxicity
NOAEL
is
>20
mg/
kg/
day
and
the
maternal
toxicity
LOAEL
was
not
identified.
No
treatment
related
effects
were
observed
in
any
dose
group
for
number
of
corpora
lutea,
number
of
implantation
sites,
live
fetuses/
dam,
pre
and
post
implantation
losses,
fetal
body
weights,
or
fetal
sex
ratios.
No
treatment
related
visceral
or
skeletal
malformations/
variations
were
observed
in
any
of
the
fetuses.
23
Therefore,
the
developmental
toxicity
NOAEL
is
>20
mg/
kg/
day
and
the
developmental
toxicity
LOAEL
was
not
identified.
This
study
is
classified
as
Unacceptable/
not
upgradable
and
does
not
satisfy
the
requirements
for
a
developmental
toxicity
study
(83
3b)
in
rabbits.
Maternal
and
developmental
toxicity
LOAELs
were
not
identified
and
the
highest
dose
did
not
approach
the
limit
dose.
Therefore,
dose
selection
was
considered
inadequate.
Doses
were
based
on
the
results
of
a
subcutaneous
study
in
the
rabbit
(MRID
00062658)
which
is
not
a
valid
method
for
selecting
doses
for
an
oral
study.
Several
other
deficiencies
were
noted
in
the
conduct
of
this
study:
percent
purity
of
the
test
article
was
not
given,
dosing
solutions
were
not
analyzed
for
concentration,
stability,
or
homogeneity,
and
much
of
the
individual
animal
data
were
not
included.
Executive
Summary:
In
a
developmental
toxicity
study
(MRID
00062658),
15
presumed
pregnant
New
Zealand
white
rabbits
per
group
following
artificial
insemination
were
administered
Lindane
(purity
and
Batch
No.
not
given)
by
subcutaneous
injection
in
corn
oil
(0.5
ml/
kg)
at
doses
of
0,
5,
15,
or
45
mg/
kg/
day
on
gestation
days
(GD)
6
18,
inclusive.
Due
to
excessive
toxicity,
the
high
dose
was
reduced
to
30
mg/
kg/
day
after
GD
9.
On
GD
29,
dams
were
sacrificed,
subjected
to
gross
necropsy,
and
all
fetuses
examined
for
visceral
and
skeletal
malformations/
variations.
Data
from
external
examination
of
the
fetuses
was
not
included.
One
mid
dose
dam
aborted
and
died
on
GD
21
and
14/
15
high
dose
animals
died
between
GD
10
and
26.
The
high
dose
group
was
then
discontinued
due
to
excessive
mortality.
Decreased
activity
and
immobilized
rear
quarters
were
observed
in
the
mid
dose
group
(frequency
and
number
affected
not
reported).
No
clinical
signs
of
toxicity
were
observed
in
the
low
dose
group.
During
GD
6
20,
does
in
the
mid
dose
group
had
a
body
weight
loss
of
126.7
g
as
compared
with
a
body
weight
gain
of
218.0
g
by
the
controls.
Body
weight
loss
was
accompanied
by
"markedly
lower"
food
consumption
by
the
mid
dose
animals.
Body
weight
changes
and
food
consumption
for
the
low
dose
group
were
similar
to
the
controls
throughout
the
study.
It
appeared
that
does
in
the
mid
and
high
dose
group
had
differences
in
the
texture
of
the
liver,
however,
data
from
gross
necropsy
were
difficult
to
interpret
due
to
poor
copy
quality
of
the
original
report.
Therefore,
the
maternal
toxicity
LOAEL
is
15
mg/
kg/
day
based
on
clinical
signs
of
toxicity,
death,
and
reduction
in
body
weight.
The
maternal
toxicity
NOAEL
is
5
mg/
kg/
day.
No
treatment
related
effects
were
observed
between
the
control
group
and
the
treated
groups
for
number
of
corpora
lutea,
number
of
implantation
sites,
live
fetuses/
dam,
pre
24
and
post
implantation
losses,
fetal
body
weights,
or
fetal
crown
rump
distances.
No
treatment
related
visceral
or
skeletal
malformations/
variations
were
observed
in
any
of
the
fetuses.
Abortion
by
one
mid
dose
doe
was
assumed
to
be
due
to
excessive
maternal
toxicity
and
not
to
a
direct
effect
on
the
embryos
or
fetuses.
Therefore,
the
developmental
toxicity
NOAEL
is
>15
mg/
kg/
day
and
the
developmental
toxicity
LOAEL
was
not
identified.
This
study
is
classified
as
Unacceptable/
not
upgradable
and
does
not
satisfy
the
requirements
for
a
developmental
toxicity
study
(83
3b)
in
rabbits.
Several
deficiencies
were
noted
in
the
conduct
of
this
study:
the
subcutaneous
route
is
not
the
preferred
method
of
administration,
excessive
toxicity
occurred
at
the
high
dose,
percent
purity
of
the
test
article
wast
not
given,
dosing
solutions
were
not
analyzed
for
concentration,
stability,
or
homogeneity,
and
much
of
the
individual
maternal
and
fetal
data
were
not
included.
However,
these
study
results
may
be
used
in
conjunction
with
the
oral
developmental
toxicity
study
in
rabbits
(MRID
42808002)
as
supplemental
information.
Study:
Developmental
Neurotoxicity
Study
Executive
Summary:
See
Short
Term
Dermal
(1
7
days);
Section
2.
3.
2
5.4
Reproductive
Toxicity
Executive
Summary:
In
a
multigeneration
reproductive
toxicity
study
(MRID
42246101),
Lindane
(99.5%
a.
i.;
Batch
No.
DA433)
was
administered
to
groups
of
30
male
and
30
female
Charles
River
CD
rats
at
dietary
concentrations
of
0,
1,
20,
or
150
ppm
(0.
087,
1.71,
and
13.05
mg/
kg/
day,
respectively)
during
the
per
mating
period
for
two
generations.
One
litter
was
produced
in
each
generation.
F1
pups
chosen
as
parental
animals
were
weaned
onto
the
same
diet
as
their
parents.
Test
or
control
diets
were
administered
to
the
F0
and
F1
parental
animals
for
71
and
70
days,
respectively,
before
the
animals
were
mated
within
the
same
dose
group.
All
animals
were
continuously
exposed
to
test
material
either
in
the
diet
or
during
lactation
until
sacrifice.
Premature
sacrifices
or
intercurrent
deaths
of
two
F0
animals
and
five
F1
animals
were
considered
incidental
to
treatment;
all
other
F0
and
F1
males
and
females
survived
to
terminal
sacrifice.
No
treatment
related
clinical
signs
of
toxicity
were
observed
in
males
or
females
of
either
generation
at
any
time
during
the
study.
No
treatment
related
effects
on
body
weights,
body
weight
gains,
food
consumption,
or
food
efficiency
were
observed
for
the
F0
and
F1
males
and
females
during
premating.
Gross
necropsy
and
hist
opathology
of
females
was
unremarkable.
During
gestation
days
10
13,
mean
body
weight
gain
by
the
high
dose
F0
females
was
significantly
reduced
(11%).
Mean
body
weight
gains
by
the
high
dose
F0
females
were
also
25
significantly
lower
on
lactation
day
1
(interval
not
specified)
as
compared
to
the
controls,
but
recovery
was
apparent
by
weaning.
No
treatment
related
changes
in
body
weights
or
body
weight
gains
were
observed
in
the
F1
females
during
gestation
or
lactation.
High
dose
male
rats
of
both
generations
had
a
significantly
(p
<
0.01)
increased
incidence
of
pale
kidneys
(10/
29
F0
males
and
10/
30
F1
males)
as
compared
with
the
controls
(0/
30
and
0/
28,
respectively).
Areas
of
change
on
the
kidneys
(not
defined)
were
observed
in
7/
29
highdose
F0
males
compared
with
2/
30
controls
and
in
4/
30
mid
dose
F1
males
and
5/
30
high
dose
F1
males
compared
with
1/
28
controls.
Significantly
(p
<
0.
01)
increased
incidence
of
hydronephrosis
was
observed
in
high
dose
F1
males
(7/
30)
as
compared
to
controls
(0/
28).
Absolute
and
relative
kidney
weights
of
the
mid
and
high
dose
F0
males
and
the
high
dose
F1
males
were
significantly
(p
<
0.01)
increased
as
compared
with
the
controls.
F0
and
F1
males
in
the
mid
and
high
dose
groups
had
significantly
(p
<
0.01)
increased
incidences
of
chronic
interstitial
nephritis,
cortical
tubular
cell
regeneration,
hyaline
droplets
in
proximal
tubules,
tubular
necrosis
with
exfoliation
and
cellular
casts,
and
cortical
tubular
casts
(n.
s.).
These
changes
are
characteristic
of
alpha
2
globulin
accumulation,
which
is
specific
to
male
rats.
Increased
absolute
and
relative
liver
weights,
accompanied
by
hepatocellular
hypertrophy,
in
the
mid
and
high
dose
males
and
females
of
both
generations
were
considered
adaptive
and
of
no
biological
significance.
Therefore,
the
LOAELfor
systemic
toxicity
is
150
ppmbased
on
decreased
body
weight
gains
by
the
F0
females
during
gestation.
The
systemic
toxicity
NOAEL
is
20
ppm.
In
addition,
the
LOAEL
for
male
rats
is
20
ppm
based
on
increased
kidney
weights
and
histopathological
lesions
in
the
kidney
characteristic
of
alpha
2u
globulin
accumulation;
the
NOAEL
for
males
is
1
ppm.
Mating,
fert
ility,
gestation
survival
(postimplantation
index),
and
liveborn
indices,
mean
precoital
interval,
and
mean
gestation
lengt
h
were
similar
between
the
treated
and
control
groups
of
both
generations.
The
sex
distribution
was
not
affected
by
the
test
material.
Mean
litter
sizes
of
the
treated
groups
were
not
different
fromthe
controls
throughout
lactation
for
both
generations.
Viability
indices
for
t
he
high
dose
F1
and
F2
pups
were
81%
and
85%,
respectively,
compared
with
96%
for
the
controls.
This
reduction
in
survival
on
lactation
day
4
was
due
to
the
death
or
sacrifice
(for
humane
reasons)
of
three
F1
litters
and
two
F2
litters.
No
treatment
related
clinical
signs
of
toxicity
were
observed
in
the
pups
of
either
generation
during
lactation.
Pup
necropsy
was
unremarkable.
Body
weights
of
the
low
and
mid
dose
F1
and
F2
pups
were
similar
to
the
controls
throughout
lactation.
Body
weights
of
the
high
dose
pups
of
both
generations
were
significantly
(p
<
0.01)
less
than
the
controls
on
lactation
days
1
and
25.
In
high
dose
F2
pups,
the
onset
and
26
completion
of
tooth
eruption
and
completion
of
hair
growth
were
significantly
(p
<
0.01)
delayed
10.5%,
11.6%,
and
24%,
respectively,
as
compared
with
the
controls.
Therefore,
the
LOAELfor
reproductive
toxicity
is
150
ppm
based
on
reduced
pup
body
weights
and
decreased
viability
in
both
generations
and
delayed
maturation
of
the
F2
pups.
The
reproductive
toxicity
NOAEL
is
20
ppm.
This
study
is
classified
as
Acceptable/
guideline
and
satisfies
the
guideline
requirements
for
a
reproduction
study
(83
4)
in
rats.
No
major
deficiencies
were
identified
in
the
conduct
of
this
study.
5.5
Additional
Information
from
Literature
Sources
Karmaus,
W.
et
al,
Reduced
Birthweight
and
Length
in
the
Offspring
of
Females
Exposed
to
PCDFs,
PCP,
and
Lindane.
Environmental
Health
Perspectives;
103(
12).
1995.
1120
1125.
The
objective
of
this
study
was
to
investigate
a
broad
range
of
adverse
health
outcomes
and
their
potential
association
to
wood
preservative
used
in
daycare
centers.
This
article
focuses
on
reproductive
effects.
A
sample
of
221
exposed
teachers
was
provided
by
the
employer's
liability
insurers.
A
comparison
group
(n
=
189)
insured
by
the
same
two
organizations
was
recruited
from
nonexposed
daycare
centers.
In
a
face
to
face
interview,
job
history
and
reproductive
history
of
398
female
teachers
were
ascertained.
Data
on
exposure
were
provided,
including
measurements
on
concentration
of
pentachlorophenol
(PCP)
and
lindane
in
wood
panels,
and
of
PCP,
lindane,
polychlorinated
dibenzo
p
dioxins
and
dibenzofurans
in
indoor
air.
An
exposure
matrix
based
on
individual
job
history,
independent
exposure
information
from
each
center,
and
reproductive
history
was
set
up
with
regard
to
the
vulnerable
time
windows
for
each
pregnancy.
Using
this
approach,
49
exposed
and
507
nonexposed
pregnancies
were
identified,
including
32
exposed
and
386
nonexposed
live
births.
For
subgroup
analyses
the
observations
were
restricted
to
independent
pregnancies,
excluding
multiple
and
consecutive
births.
The
data
were
analyzed
with
linear
regression
techniques,
taking
confounders
into
account.
The
crude
median
difference
between
exposed
and
nonexposed
was
175
g
in
birthweight
and
2
cm
in
length.
Controlling
for
confounders,
the
results
showa
significantly
reduced
but
weight
(p
=
0.04)
and
length
(p
=
0.02)
in
exposed
pregnancies,
even
after
restricting
the
data
to
independent
pregnancies
and
pregnancies
for
which
data
could
be
validated
from
the
mother's
health
cards.
These
differences
were
not
explained
by
differences
in
gestational
age
indicating
that
a
toxic
effect,
which
could
cause
small
for
date
newborns,
might
have
affected
the
fetus.
Rivera,
S.
et
al,
Behavioral
Changes
Induced
in
Developing
Rats
by
an
Early
Postnatal
Exposure
to
Lindane.
Neurotoxicity
and
Teratology,
12(
6).
1990.
591
595
The
purpose
of
this
studywas
to
determine
whether
the
behavioral
developmental
pattern
was
altered
by
an
early
postnatal
exposure
to
lindane.
Male
and
female
offspring
of
Wist
ar
rat
s
27
were
daily
orally
administered
with
a
nonconvulsant
dose
of
lindane
(10
mg/
kg)
during
7
days
either
the
1st
or
the
2nd
postnatal
week
days.
Effects
on
pups
were
evaluated
with
a
reduced
developmental
neurotoxicological
test
battery.
Body
weight
evolution,
neuromotor
reflexes
(surface
righting,
cliff
avoidance
and
tail
hang
reflex)
and
spontaneous
motor
activity
were
analyzed
from
day
1
after
birth
up
to
day
28.
The
body
weight
pattern
was
unaffected
by
treatment
with
lindane
and
no
signs
of
overt
toxicity
were
observed.
Lindane
treated
pups
showed
an
increased
positive
response
of
the
neuromotor
reflexes.
Furthermore,
lindane
produced
hyperactivity,
especially
manifested
between
days
12
and
16.
Apeak
of
activity
was
reached
at
day
16
in
lindane
treated
group,
while
control
animals
had
a
maximum
between
days
20
and
24.
These
results
suggest
that
low
nonconvulsant
doses
of
lindane
may
induce
behavioral
changes
in
developing
rats.
Sircar,
S.
et
al,
Lindane
(gamma
HCH)
Causes
Reproductive
Failure
and
Fetotoxicity
in
Mice.
Toxicology
59(
2).
1989.
171
177.
Lindane
(gamma
Hexachlorocyclohexane)
was
orally
given
to
pregnant
Swiss
female
mice
at
various
stages
of
pregnancy.
During
early
pregnancy
(1
4
days
of
gestation),
the
insecticide
caused
total
absence
of
any
implantation
site,
while
given
during
mid
pregnancy
(6
12
days
of
gestation),
lindane
caused
total
resorption
of
fetuses.
Lindane
administration
during
late
pregnancy
(14
19
days
of
gestation)
resulted
in
death
of
all
pups
either
within
12
h
(high
dosed
group)
or
5
days
(low
dosed
group)
of
parturition.
Body
weight
of
such
pups
were
also
highly
reduced.
When
estrogen
was
given
together
with
lindane
at
early
pregnancy,
implantation
was
normal,
although
subsequent
fetal
development
was
adversely
affected.
Progesterone,
unlike
estrogen,
could
not
correct
lindane
induced
failure
in
implantation.
On
the
other
hand,
when
estrogen
and
progesterone
were
simultaneously
given
to
lindane
fed
mice
during
early
pregnancy,
both
implantation
and
subsequent
fetal
development
became
comparable
to
normal
mice.
The
insecticide
besides
being
fetotoxic,
thus
appears
to
cause
steroid
hormone
deficiency
resulting
in
reproductive
and
developmental
failure.
Pompa,
G.
et
al,
Transfer
of
Lindane
and
Pentachlorobenzene
From
Mother
to
Newborn
Rabbits,
Pharmacology
and
Toxicology;
74(
1).
1994.
28
34.
After
administration
of
gamma
hexachlorocyclohexane
(lindane)
(30
mg/
kg)
to
sixteen
pregnant
rabbits,
the
transfer
and
distribution
of
this
insecticide
and
its
metabolite
pentachlorobenzene,
in
foetuses
and
newborns
at
the
5th,
10th
and
20th
days
after
birth,
were
investigated.
Over
one
lactation
the
mothers
excreted
via
the
milk
about
30%
of
the
lindane
present
in
tissues
at
the
28
th
day
of
pregnancy.
The
total
amount
of
lindane
transferred
via
milk
to
5
day
old
newborns
was
higher
than
that
transferred
across
the
placenta
during
pregnancy.
Lindane
concentrations
in
newborns
decreased
in
spite
of
the
efficient
transfer
to
off
spring
by
lactating
mothers.
This
cannot
be
explained
by
growth
alone
and
indicates
that
newborns
are
able
to
actively
metabolize
the
insecticide.
The
pentachlorobenzene
metabolite
produced
after
lindane
administration
to
the
mothers
crossed
the
placental
barrier
with
difficulty
during
pregnancy,
but
was
readily
transferred
to
off
spring
via
milk.
Pentachlorobenzene
levels
in
28
neonates
increased
during
lactation
by
transfer
and
also
as
a
consequence
of
endogenous
production.
At
the
20th
day
of
lactation
the
pentachlorobenzene
concentration
in
maternal
and
foetal
tissues
was
higher
than
that
of
lindane.
5.6
Determination
of
Susceptibility
No
quantitative
or
qualitative
evidence
of
increased
susceptibility
of
rat
or
rabbit
fetuses
to
in
utero
exposure
in
developmental
toxicitystudies.
Inthe
two
generation
reproductive
study,
there
was
qualitative
evidence
of
an
increased
susceptibility
to
exposure
to
lindane
by
pups.
In
the
parental
animals,
toxicity
was
seen
in
the
form
of
reduction
in
body
weight
gain
during
gestation
while
offspring
toxicity
was
correlated
with
decreases
in
pup
viability
and
pup
body
weight
in
the
F1
and
F2
generations
as
well
as
delayed
maturation
in
the
F2
generation.
Evidence
for
quantitative
increase
in
susceptibility
could
not
be
ascertained
due
to
the
wide
spread
in
the
doses
tested.
In
the
DNT
study,
there
is
supporting
evidence
of
a
qualitative
and
quantitative
increase
in
susceptibility.
At
the
high
dose
(13.
7
mg/
kg/
day)
,
animals
in
t
he
F0
generation
have
a
reduced
body
weight
and
body
weight
gain
while
at
the
mid
dose
(5.6
mg/
kg/
day)
F1
and
F2
animals
have
a
reduced
survival
rate,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation
as
compared
to
controls.
The
open
literature
also
contains
citations
which
suggest
an
increase
in
susceptibility
of
fetuses
and
young
animals
to
exposure
to
lindane
(see
Section
5.
5).
6
HAZARD
CHARACTERIZATION
Lindane
is
a
moderately
toxic
compound
in
EPA
toxicity
class
II.
It
is
neither
an
eye
nor
dermal
sensitizer.
Labels
for
products
containing
it
must
bear
the
Signal
Word
WARNING.
Some
formulations
of
lindane
are
classified
as
Restricted
Use
Pesticides
(RUP),
and
as
such
may
only
be
purchased
and
used
by
certified
pesticide
applicators.
Lindane
is
no
longer
manufactured
in
the
U.
S.,
and
most
agricultural
and
dairy
uses
have
been
canceled
by
the
EPA
because
of
concerns
about
the
compound's
potential
to
cause
cancer.
The
primary
effect
of
Lindane
is
on
the
nervous
system;
in
both
acute,
subchronic,
and
developmental
neurotoxicity
studies
and
chronic
toxicity/
oncogenicity
study,
Lindane
appears
to
cause
neurotoxic
effects
including
tremors,
convulsions
and
hypersensitivity
to
touch.
This
is
further
corroborated
by
the
published
literature
in
which
human
exposure
has
been
seen
to
produce
neurologic
effects.
Lindane
also
causes
renal
and
hepatic
toxicity
via
the
oral,
dermal
and
inhalation
routes
of
exposure
as
seen
in
subchronic,
2
generation
reproduction
and
chronic
toxicity
studies
in
the
rat.
In
developmental
toxicity
studies,
no
developmental
effects
were
seen
at
levels
where
maternal
toxicity
was
evident.
In
the
rat
developmental
study,
the
developmental
effects
(extra
rib
and
total
skeletal
variations)
were
seen
at
dose
levels
(20
mg/
kg/
day)
greater
than
maternal
toxicity
(10
29
mg/
kg/
day).
In
the
reproductive
toxicity
study,
both
systemic
and
developmental
LOAELs
are
13
mg/
kg;
however
a
qualitative
difference
in
maternal
and
offspring
effects
(reduced
body
weight
of
maternal
animals
and
reduced
viability
and
delayed
maturation
in
pups)
indicates
an
increased
susceptibility
to
exposure.
This
is
further
corroborated
by
a
developmental
neurotoxicity
study
in
which
a
qualitative
and
quantitative
increase
in
susceptibility
is
seen.
At
the
high
dose
(13.
7
mg/
kg/
day)
,
animals
in
the
F0
generation
have
a
reduced
body
weight
and
body
weight
gain
while
at
the
mid
dose
(5.6
mg/
kg/
day)
F1
and
F2
animals
have
a
reduced
survival
rate,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation
as
compared
to
controls.
According
to
the
TES
committee
report
(1994,
Doc
013460),
Lindane
has
not
been
classified
by
the
HED
Cancer
Peer
Review
Committee.
It
was
determined
by
the
RfD/
Peer
Review
Committee
(8/
25/
93)
that:
"The
mouse
carcinogenicity
data
were
considered
insufficient
because
of
major
deficiencies
associated
with
all
studies
available."
Lindane
however
had
been
previously
classified
by
the
Cancer
Assessment
Group
of
the
Office
of
Research
and
Development
(memorandum
dated
7/
23/
85
from
R.
E.
McGaughy
to
Anne
Barton)
as
a
group
B2/
C
carcinogen
based
on
increased
incidence
of
mouse
liver
tumors.
The
upper
bound
slope
of
the
dose
response
was
given
in
that
memorandumas
Q1*
=
1.1
(mg/
kg/
day)
1
.
Anew
mouse
oncogenicitystudyis
expected
in
December
2000.
Lindane
does
not
appear
to
be
mutagenic.
The
available
mutagenicity
studies
are
negative;
they
include
a
dominant
lethal
mutation
assay,
sister
chromatid
exchange
assay
and
mammalian
cell
culture
gene
mutation
in
V79
cells.
IPCS
also
states
that
Lindane
does
not
appear
to
have
mutagenic
potential.
7
DATA
GAPS
none
30
8
ACUTE
TOXICITY
STUDY
TYPE
MRID
CATEGORY
RESULT
81
1
Acute
oral
00049330
II
LD50
88
mg/
kg
males
91
mg/
kg
females
81
2
Acute
dermal
00109141
II
LD50
1000
mg/
kg
males
900
mg/
kg
females
81
3
Acute
inhalation
Acc.
263946
III
LC50
1.56
mg/
L
both
sexes
81
4
Eye
irritation
Acc.
263946
III
PIS
=
0.6
no
corneal
involvement
irritation
cleared
after
24
hours
81
5
Dermal
irritation
Acc.
263946
IV
PIS
=
0
not
an
irritant
81
6
Dermal
sensitization
Acc.
263946
NA
not
a
sensitizer
31
9
TOXICOLOGIC
PROFILE
EXPOSURE
SCENARIO
DOSE
(mg/
kg/
day)
ENDPOINT
STUDY
TYPE/
MRID
Acute
Dietary
general
population
NOAEL=
6
mg/
kg
UF
=
100
LOAELis20
mg/
kgbased
on
increasedgrip
strength,
increased
Motor
Activity
Acute
Neurotoxicity
in
Rats/
44769201
Acute
Dietary
females
13
50
NOAEL=
N/
A
UF
=
N/
A
No
relevant
single
exposure
endpoint
was
identified.
N/
A
Acute
RfD
(Gen.
Pop.)
=
0.
06
mg/
kg/
day
Acute
RfD
(Females
13
50)
=
N/
A
Chronic
Dietary
NOAEL=
10
ppm
(0.
47
mg/
kg/
day)
UF
=
100
LOAEL
is
100
ppm
(4.
81
mg/
kg/
day)
periacinar
hepatocyte
hypertrophy,
increased
liver/
spleen
weigt,
increased
platelets
Chronic
Feeding
and
Carcinogenicity
in
Rats
41094101
41853701
42891201
Chronic
RfD
=
0.
047
mg/
kg/
day
Cancer
Risk
3
Q1*=
1.1
(mg/
kg/
day)
1
Short
Term
1
(Dermal)
NOAEL=
10
ppm
(1.
2
mg/
kg/
day)
LOAEL
is
50
ppm
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
Developmental
Neurotoxicity
Study
in
Rats
45073501
Intermediate
Term
1
(Dermal)
NOAEL=
10
ppm
(1.
2
mg/
kg/
day)
LOAEL
is
50
ppm
based
on
reduced
pup
survival,
decreased
body
weights
and
body
weight
gains
during
lactation,
increased
motor
activity,
and
decreased
motor
activity
habituation.
Developmental
Neurotoxicity
Study
in
Rats
45073501
Long
Term
1
(Dermal)
NOAEL=
10
ppm
(0.
47
mg/
kg/
day)
LOAEL
is
100
ppm
(4.
81
mg/
kg/
day)
periacinar
hepatocyte
hypertrophy,
increased
liver/
spleen
weigt,
increased
platelets
Chronic
Feeding
and
Carcinogenicityin
Rats
41094101
41853701
42891201
Dermal
Absorption
Factor
=
10%
Short
Term
1
(Inhalation)
0.5
mg/
m
3
(0.
13
mg/
kg/
day)
based
on
clinical
signs
(diarrhea,
piloerection)
seen
at
day
14
and
continuing
for
20
days
90
Day
Inhalation
Toxicity
00255003
Intermediate
Term
1
(Inhalation)
0.5
mg/
m
3
(0.
13
mg/
kg/
day)
increased
kidney
weights
in
females
and
bone
marrow
effects
(incr.
reticul,
incr
myelo,
decr.
lympho.)
90
Day
Inhalation
Toxicity
00255003
Long
Term
2
(Inhalation)
N/
A
N/
A
N/
A
1
An
MOE
of
100
was
selected
2
Exposure
thru
this
route
for
this
duration
is
not
expected
3
The
Cancer
Risk
will
be
re
evaluated
upon
review
of
the
Mouse
Carcinogenicity
Study
submitted
in
December
2000
32
| epa | 2024-06-07T20:31:43.115051 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0202-0010/content.txt"
} |
EPA-HQ-OPP-2002-0202-0011 | Supporting & Related Material | "2002-08-14T04:00:00" | null | CANCER
ASSESSMENT
DOCUMENT
EVALUATION
OF
THE
CARCINOGENIC
POTENTIAL
OF
LINDANE
PC.
Code:
009001
Final
Report
November
29,
2001
CANCER
ASSESSMENT
REVIEW
COMMITTEE
HEALTH
EFFECTS
DIVISION
OFFICE
OF
PESTICIDE
PROGRAMS
ii
DATA
PRESENTATION:
Suhair
Shallal,
Toxicologist
DOCUMENT
PREPARATION:
Sanjivani
Diwan,
Executive
Secretary
COMMITTEE
MEMBERS
IN
ATTENDANCE:
(Signature
indicates
concurrence
with
the
assessment
unless
otherwise
stated).
Karl
Baetcke
William
Burnam
Marion
Copley
Kerry
Dearfield
Vicki
Dellarco
Virginia
Dobozy
Richard
Hill
Yiannakis
Ioannou
Tim
McMahon
Nancy
McCarroll
Esther
Rinde
Jess
Rowland
Joycelyn
Stewart
Clark
Swentzel
Linda
Taylor
Yin
Tak
Woo
NON
COMMITTEE
MEMBERS
IN
ATTENDANCE
(Signature
indicates
concurrence
with
the
pathology
report
and
statistical
analysis
of
data,
respectively)
John
M.
Pletcher,
Pathology
Consultant
Lori
Brunsman,
Statistical
Analysis
ii
CONTENTS
ExecutiveSummary.............................................................
.iii
I.
Introduction...............................................................
..
1
II.
BackgroundInformation
...................................................
1
III.
Evaluation
of
Carcinogenicity
...............................................
2
1.
CombinedChronicToxicity&
CarcinogenicityStudyinCD
1Mice..............
2
2.
CarcinogenicityStudyinAgouti,
PseudoAgoutiandBlackMice................
7
3.
NTPCarcinogenicityStudyinB6C3F1Mice
...............................
8
4.
CarcinogenicityStudyinWistarRats
....................................
11
5.
NTPChronicToxicity&
CarcinogenicityStudyinOsborne
MendelRats.........
13
IV.
Toxicology............................................................
14
1.
Metabolism
.......................................................
14
2.
Mutagenicity
......................................................
15
3.
StructureActivityRelationship.........................................
16
4.
SubchronicandchronicToxicity
.......................................
16
5.
ModeofActionStudies
..............................................
18
V.
Committee'sAssessmentoftheWeight
of
theEvidence
..........................
19
VI.
ClassificationofCarcinogenicPotential
.......................................
22
VII.
QuantificationofCarcinogenicPotential.......................................
22
V.
Bibliography...........................................................
23
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
iii
EXECUTIVE
SUMMARY
Lindane
(gamma
isomer
of
hexachlorocyclohexane,
HCH)
has
been
previously
classified
by
the
Cancer
Assessment
Group
of
the
Office
of
Research
and
Development
(CAG/
ORD,
1985)
as
a
group
"B2/
C"
carcinogen
based
on
an
increased
incidence
of
mouse
liver
tumors.
In
1993,
the
RfD/
Peer
Review
Committee
(1993)
determined
that
the
mouse
carcinogenicity
data
were
inadequate
because
of
major
deficiencies
associated
with
the
available
studies.
The
Toxicology
Endpoint
Selection
(TES)
Committee
concluded
that
a
new
carcinogenicity
study
in
mice
was
needed
to
make
a
determination
of
the
carcinogenic
potential
of
lindane
(
TES,
1994).
On
May30,
2001,
the
Cancer
Assessment
ReviewCommittee
(CARC)
of
the
Health
Effects
Division
(HED)
of
the
Office
of
Pesticide
Programs
met
to
evaluate
the
carcinogenic
potential
of
lindane.
At
this
meeting,
the
CARC
could
not
make
a
determination
of
the
carcinogenic
potential
of
lindane
because
the
NTP
studies
were
limited
in
value
and
it
was
uncertain
if
the
study
on
Agouti,
Pseudoagouti
and
Black
mice
with
limited
data
could
be
used
for
regulatory
purposes.
In
addition,
the
CARC
was
informed
that
new
histopathology
data
would
be
submitted.
The
Committee
also
requested
additional
information
including
results
of
a
90
day
subchronic
range
finding
study
in
CD1
mice,
an
earlier
RfD
Committee
report
and
analyses
of
the
older
studies
on
lindane.
At
the
September
13,
2001
meeting,
the
Committee
reevaluated
all
the
available
information/
data
including
the
old
and
the
newly
gathered
information
that
was
previously
not
available
for
review.
[A
list
of
CARC
members
who
attended
one
or
both
meetings
on
lindane
is
presented
on
page
#
i.
These
meetings
were
held
jointly
by
teleconference
with
Pesticide
Management
Regulatory
Agency
(PMRA),
HealthCanada,
Canada].
The
chronic
toxicity/
carcinogenicitystudies
were
conducted
using
5
different
strains
of
mice
and
two
strains
of
rats.
The
dietary
doses
administered
in
these
studies
were
as
follows:
·
CD
1
mice
(50/
sex/
dose):
0,
10,
40,
or
160
ppm.
for
78
weeks
(0,
1.3,
5.2,
and
21
mg/
kg/
day
for
males
and
0,
1.
8,
7.
1,
and
26.
8
mg/
kg/
day
for
females,
respectively).
Female
Agouti,
Pseudoagouti
and
Black
mice
(36
96
animals
per
strain):
0
or
160
ppm.
for
24
months
B6C3F1
mice
(50
/sex/
dose):
0,
80
or
160
ppm
for
80
weeks
Wistar
rats
(50/
sex/
dose):
0,
1,
10,
100,
or
400
ppm
for
2
years
(
0,
0.05,
0.47,
4.81,
and
19.66
mg/
kg/
day
for
males
and
0,
0.06,
0.59,
6.00,
and
24.34
mg/
kg/
day
for
females,
respectively).
Osborne
Mendel
rats
(50/
sex/
dose):
For
males:
320
or
640
ppm
for
38
weeks
and
160
or
320
ppm
for
the
remaining
42
weeks.
For
females:
320
or
640
ppm
for
2
weeks
and
160
or
320
ppm
for
49
weeks
then
for
the
remaining
29
weeks
the
dose
was
lowered
to
80
or
160
ppm.
Matched
controls
consisted
of
10/
sex.
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
iv
The
CARC
concluded
that
lindane
was
carcinogenic
only
to
female
CD
1
mice
based
on
the
following:
!
CD
1
female
mice
had
significant
increasing
trends,
and
significant
differences
in
the
pair
wise
comparisons
of
the
160
ppm(
26.8
mg/
kg/
day)
dose
group
with
the
controls,
for
lung
alveolarbronchiolar
adenomas
and
combined
adenomas/
carcinomas,
all
at
p
<
0.
05.
The
incidence
of
lung
adenomas
was
slightly
outside
the
historical
control
range.
However,
the
increased
incidence
of
carcinomas
was
not
dose
dependent
and
the
tumor
response
was
variable.
Lindane
was
not
carcinogenic
to
male
mice.
The
dosing
at
the
highest
level
was
adequate
and
not
excessive
based
on
increased
incidences
of
centrilobular
hepatocellular
hypertrophy
and
eosinophilic
foci
of
cellular
alteration
in
males
and
a
slight
increase
in
bronchiolar
alveolar
adenomas
in
females.
!
At
160
ppm,
both
the
treated
female
Agouti
and
Pseudoagouti
mice
had
an
increase
in
benign
lung
adenomas;
the
treated
Agouti
mice
also
had
an
increased
incidence
of
liver
adenomas.
No
statistical
analyses
of
tumor
data
were
conducted.
There
was
no
increase
in
the
incidence
or
decrease
in
latency
period
for
liver
tumors
in
Black
and
Pseudoagouti
strains
of
mice.
There
was
evidence
of
increased
liver
weights
and
an
increased
incidence
of
Clara
cell
hyperplasia
in
Agouti
and
Black
strains
of
mice.
However,
the
study
was
conducted
on
few
animals,
only
a
single
dose
and
sex
were
tested,
no
statistical
analyses
of
tumor
data
were
presented
and
the
results
of
the
study
were
not
adequately
reported.
The
Committee
concluded
that
although
the
liver
effects
appear
to
suggest
that
a
dose
of
160
ppm
was
adequate,
additional
dose
groups
could
have
provided
confirmatory
information.
!
The
CARC
could
not
assess
the
carcinogenicity
of
lindane
in
B6C3F1
male
and
female
mice
because
the
data
reporting
was
inadequate
and
there
were
no
indications
of
toxicity
in
high
dose
females.
Moreover,
the
use
of
only
10
mice
per
sex
for
the
control
group
compromised
the
usefulness
of
the
study.
The
Committee
concluded
that
the
increased
incidence
of
lung
tumors
in
female
mice
of
three
strains
was
treatment
related
because
the
statistically
significant
increase
in
lung
adenomas
in
female
CD
1
mice
was
corroborated
with
the
increase
in
lung
tumors
in
two
genetically
susceptible
strains
of
mice.
Although
there
is
some
evidence
of
liver
tumor
induction
in
these
genetically
susceptible
strains
of
mice,
no
evidence
of
liver
tumors
was
noted
in
CD
1
mice.
Nevertheless,
the
evidence
of
hepatotoxicity
(increased
liver
weight,
hypertrophy
and
increased
incidence
of
liver
foci
in
both
sexes)
and
promoting
activity,
indicates
t
hat
t
he
liver,
in
addition
to
lung
is
a
major
target
organ
of
toxicity.
!
The
CARC
determined
that
lindane
was
not
carcinogenic
to
male
and
female
Wistar
rats
and
the
results
of
the
study
in
Osborne
Mendel
rats
were
difficult
to
interpret
and
were
not
useful
in
determining
the
carcinogenic
potential
of
lindane
in
that
strain
of
rat.
!
The
results
of
a
battery
of
acceptable
mutagenicity
assays
indicate
that
lindane
has
a
low
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
v
concern
for
mutagenicity.
These
studies
satisfy
pre
1991
FIFRAguideline
requirements.
The
Committee
recommended
that
the
dominant
lethal
assay
be
repeated
to
determine
if
there
is
a
genetic
component
to
the
reproductive
(germ
cell)
effects
reported
for
lindane.
!
The
technical
HCH
and
the
alpha
isomer
are
classified
as
category
"B2"
(probable
human
carcinogen).
The
beta
isomer
is
classified
as
a
group
"C
"(
possible
human
carcinogen)
while
the
delta
and
epsilon
isomers
are
classified
as
group
"D"
(not
classifiable
as
to
human
carcinogenicity)
.
!
No
mechanistic
studies
were
submitted
to
support
the
mode
of
action
for
lung
tumor
induction
in
mice.
In
accordance
with
the
EPADraft
Guidelines
for
Carcinogen
Risk
Assessment
(July,
1999),
the
CARC
classified
lindane
into
the
category
"Suggestive
evidence
of
carcinogenicity,
but
not
sufficient
to
assess
human
carcinogenic
potential"
because
lindane
caused
an
increased
incidence
of
benign
lung
tumors
in
female
mice
only.
The
Committee
further
recommended
that
quantification
of
human
cancer
risk
is
not
required.
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
1
Cl
Cl
Cl
Cl
Cl
Cl
I.
INTRODUCTION
Lindane
(gamma
isomer
of
hexachlorocyclohexane,
HCH)
was
previously
classified
by
the
Cancer
Assessment
Group
of
the
ORD
(1985)
as
a
group
"B2/
C"
carcinogen
based
on
an
increased
incidence
of
mouse
liver
tumors;
the
calculated
unit
risk
(
Q1*)
was
1.
1
(mg/
kg/
day)
1
human
equivalents.
The
other
isomers
of
hexachlorocyclohexane
are
classified
in
IRIS.
Technical
HCH
and
the
alpha
isomer
are
classified
as
"B2",
probable
human
carcinogens.
The
beta
isomer
is
classified
as
"C",
possible
human
carcinogen.
The
delta
and
epsilon
isomers
are
classified
as
D,
not
classifiable
as
to
human
carcinogenicity.
In
1993,
the
RfD/
Peer
Review
Committee
determined
that
the
mouse
carcinogenicity
data
were
insufficient
because
of
major
deficiencies
associated
with
all
available
studies.
The
TES
committee
concluded
that
a
new
carcinogenicity
study
in
mice
was
needed
to
make
a
determination
of
the
carcinogenic
potential
of
lindane
(TES,
1994).
On
May
30,
2001,
the
HED
Cancer
Assessment
Review
Committee
(CARC)
of
the
Health
Effects
Division
(HED)
of
the
Office
of
Pesticide
Programs
met
to
evaluate
the
carcinogenic
potential
of
lindane.
At
this
meeting,
the
CARC
could
not
make
a
determination
of
the
carcinogenic
potential
of
lindane
because
the
NTP
studies
were
limited
in
value
and
the
published
study
on
Agouti,
Pseudoagouti
and
Black
mice
could
not
be
used
for
regulatory
purposes.
The
Committee,
therefore,
requested
additional
information
including
results
of
a
90
day
subchronic
range
finding
studyin
CD
1
mice,
an
earlier
RfD
Committee
report
and
analyses
of
the
older
studies
on
lindane.
At
the
September
13,
2001
meeting,
the
Committee
met
to
reevaluate
the
carcinogenic
potential
of
lindane
based
on
the
available
old
and
new
information/
data.
At
this
meeting,
information/
data
were
presented
by
Dr.
Suhair
Shallal
of
Reregistration
Branch
4.
These
data
included
a
new
mouse
carcinogenicity
study
in
CD
1
mice
submitted
by
the
registrant,
a
published
study
in
Agouti,
Pseudoagouti
and
Black
mice,
NCI
studies
in
B6C3F1
mice
and
Osborne
Mendel
rats
and
a
2
year
chronic/
carcinogenicity
study
in
Wistar
rats.
In
addition,
carcinogenicity
and
genetic
toxicology
data
on
structurally
related
compounds
were
presented.
II.
BACKGROUND
INFORMATION
Lindane
(PC.
Code
is
009001
and
CAS
Number
is
58
89
9)
is
a
broad
spectrum
organochlorine
compound
used
on
a
wide
range
of
soil
dwelling
and
plant
eating
(phytophagous)
insects.
Its
chemical
structure
is
provided
below.
Figure
1.
Chemical
Structure
of
HCH
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
2
The
technical
HCH
consists
of
isomer:
65
67%
,
isomer:
11
13%,
isomer:
13
15%
,
isomer:
3
5%,
isomer:
4
6%
and
other
isomers:
<1%.
Lindane
is
a
isomer
(1
2
3
4 ,
5 ,
6
hexachlorocyclohexane).
The
other
isomers
are:
isomer
(1
2
3
4 ,
5 ,
6
hexachlorocyclohexane);
isomer
(1
2
3
4 ,
5 ,
6
hexachlorocyclohexane);
isomer
(1
2
3
4 ,
5 ,
6
hexachlorocyclohexane)
and
isomer:
(1
2
3
4 ,
5 ,
6
hexachlorocyclohexane).
Worldwide,
lindane
is
commonly
used
on
a
wide
variety
of
crops,
in
warehouses,
in
public
health
to
control
insect
borne
diseases,
and
(with
fungicides)
as
a
seed
treatment.
Lindane
is
also
presently
used
in
lotions,
creams,
and
shampoos
for
the
control
of
lice
and
mites
(scabies)
in
humans;
these
pharmaceutical
uses
are
regulated
by
FDA.
In
the
U.
S.,
the
only
registered
food/
feed
use
is
seed
treatment
for
field
and
vegetable
crops.
Lindane
may
be
found
in
formulations
with
a
host
of
fungicides
and
insecticides.
Labels
for
products
containing
the
chemical
must
bear
the
Signal
Word
WARNING.
Some
formulations
of
lindane
are
classified
as
Restricted
Use
Pesticides
(RUP),
and
as
such
may
only
be
purchased
and
used
by
certified
pesticide
applicators.
Lindane
is
no
longer
manufactured
in
the
U.
S.,
and
most
agricultural
and
dairy
uses
have
been
canceled
because
of
concerns
about
its
potential
carcinogenicity.
III.
EVALUATION
OF
CARCINOGENICITY
STUDIES
1.
Combined
Chronic
Toxicity/
Carcinogenicity
Study
with
Lindane
in
CD
1
Mice
Reference:
Lindane,
carcinogenicity
study
by
dietary
administration
to
CD
1
mice
for
78
weeks
(2000),
final
report
(vols.
1
4).
Huntingdon
Life
Sciences
Ltd.,
Woolley
Road,
Alconbury,
Huntingdon,
Cambridgeshire,
PE28
4HS,
England,
Report
no.
00
3512,
Huntingdon
Life
Sciences
Project
identity
no.
CIL/
021,
MRID
45291402.
Experimental
Design
Lindane
(99.78%
a.
i.,
batch
no.
HLS
96/
1)
was
administered
to
groups
of
50
Crl:
CD
1
®
(ICR)
BR
mice/
sex/
dose
in
the
diet
at
concentrations
of
0,
10,
40,
or
160
ppm.
The
test
diets
were
given
for
78
weeks.
The
concentrations
of
10,
40,
or
160
ppm
resulted
in
mean
daily
compound
intakes
for
males
of
1.
3,
5.
2,
and
21
mg/
kg/
day
and
for
females
of
1.8,
7.1,
and
27
mg/
kg/
day,
respectively.
Discussion
of
Tumor
Data
Tumor
Analyses
As
shown
in
Table
1.
there
was
no
statistically
significant
increase
in
tumors
in
male
mice
(Brunsman,
2001).
The
incidence
of
liver
tumors
was
not
statistically
significant
in
either
male
or
female
CD
1
mice(
Table
1).
Table
1.
CD
1
Mice
Male
and
Female
Liver
Tumor
Rates
+
and
Exact
Trend
Test
and
Fisher's
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
3
Exact
Test
Results
(p
values)
(Brunsman
2001)
ppm
0
10
40
160
0
10
40
160
mg/
kg/
day
0
1.
3
5.2
20.5
0
1.8
7.
1
26.8
Males
females
Tumor
Type
Liver
Tumor
Adenoma
%
p
=
10
a
/48
(21)
0.1730
10/
46
(22)
0.5570
9/
43
(21)
0.5962
13/
46
(28)
0.2752
0/
47
(0)
0.2567
0/
45
(0)
1.000
0/
47
(0)
1.000
1
a
/48
(2)
0.5053
Carcinoma
%
p
=
4/
48
(8)
0.4046
1/
46
(2)
0.1943
1/
43
(2)
0.2167
2
b
/46
(4)
0.3592
No
carcinomas
were
observed
in
females
Combined
%
p
=
13/
48
(27)
0.1817
11/
46
(24)
0.4543
10/
43
(23)
0.4304
15/
46
(33)
0.3594
+
Number
of
tumor
bearing
animals/
Number
of
animals
examined,
excluding
those
that
died
before
week
53.
a
First
adenoma
observed
in
males
at
week
67,
dose
0
ppm;
First
adenoma
observed
in
females
at
week
80,
dose
160
ppm
b
First
carcinoma
observed
in
males
at
week
53,
dose
10
ppm;
no
carcinomas
were
observed
in
females.
Note:
Significance
of
trend
denoted
at
control.
Significance
of
pair
wise
comparison
with
control
denoted
at
dose
level.
If
*
,
then
p
<
0.05.
If
**
,
then
p
<
0.01.
Treatment
for
up
to
78
weeks
with
lindane
resulted
in
a
statistically
significant
increase
in
the
incidence
of
bronchiolar
alveolar
adenomas
and
an
increased
incidence
of
carcinomas
in
female
Crl:
CD
1
mice;
however,
the
increased
incidence
of
carcinomas
was
not
dosedependent
and
tumor
response
was
variable.
Female
mice
had
significant
increasing
trends
and
significant
differences
in
the
pair
wise
comparisons
of
the
160
ppm
dose
group
with
the
controls
for
lung
alveolar
bronchiolar
adenomas
and
combined
adenomas/
carcinomas,
all
at
p
<
0.
05
(Table
2a).
The
incidence
of
pulmonary
adenomas
in
the
control
group
was
at
the
low
end
of
the
range
in
historical
controls
(6%)
and
the
incidence
in
females
administered
the
high
dose
(23%)
was
slightly
outside
of
the
high
end
of
the
range
for
the
historical
controls
(6%
19%)
(MRID
45291402).
.
Table
2a.
Male
and
Female
Lung
Alveolar
Bronchiolar
Tumor
Rates
+
and
Exact
Trend
Test
and
Fisher's
Exact
Test
Results
(p
values)
Initial
Diagnosis
(Brunsman,
2001)
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
4
ppm
0
10
40
160
0
10
40
160
mg/
kg/
day
0
1.
3
5.2
20.5
0
1.8
7.
1
26.8
males
females
Tumor
Type
Lung
Alveolar
Bronchiolar
Tumors
Adenoma
%
p
=
16
a
/49
(33)
0.0270*
n
15/
48
(31)
0.5278
11/
49
(22)
0.1830
8/
48
(17)
0.0554
3
a
/48
(6)
0.0274
*
7/
46
(15)
0.1412
7/
47
(15)
0.1497
11/
48
(23)
0.0200
*
Carcinoma
%
p
=
0/
49
(0)
0.3138
1/
48
(2)
0.4948
3
b
/49
(6)
0.1211
0/
48
(0)
1.0000
1/
48
(2)
0.4361
2
b
/46
(4)
0.4839
2/
47
(4)
0.4920
1/
48
(2)
0.7526
Combined
%
p
=
16/
49
(33)
0.0186*
n
16/
48
(33)
0.5574
14/
49
(29)
0.4134
8/
48
(17)
0.0554
4/
48
(8)
0.0389
*
8/
46
(17)
0.1573
9/
47
(19)
0.1080
12/
48
(25)
0.0264
*
a
first
adenoma
observed
in
males
at
week
33,
dose
0
ppm
and
in
females
at
week
44,
dose
0
ppm
b
first
carcinoma
observed
males
at
week
65,
dose
40
ppm
and
in
females
at
week
53,
dose
10
ppm
n
Negative
trend
Note:
Significance
of
trend
denoted
at
control.
Significance
of
pair
wise
comparison
with
control
denoted
at
dose
level
If
*
,
then
p
<
0.05.
If
**
,
then
p
<
0.01.
A
new
report
on
the
results
of
resectioning
of
lungs
of
female
mice
was
later
submitted
by
the
Registrant
(MRID
45470601).
The
results
showed
the
presence
of
two
additional
pulmonary
adenomas
in
the
controls
and
two
in
the
high
dose
group.
The
number
of
pulmonary
adenomas
and
combined
adenomas/
carcinomas
in
Group
4
remained
still
statistically
significant
(Table
2b),
and
was
biologically
significant,
being
well
above
the
historical
control
range
for
this
strain
of
mouse.
The
incidence
in
the
controls
and
in
the
two
intermediate
dose
groups
was
within
the
historical
control
range
(6%
19%)
for
pulmonary
adenomas
in
CD
1
females.
It
is,
however,
difficult
to
compare
old
tumor
data
versus
the
combined
analyses
based
on
the
old
and
new
findings
without
knowing
the
exact
procedure
involved
in
resectioning
the
lungs
and
why
resectioning
of
the
lung
tissue
was
necessary.
Therefore,
without
judging
the
validity
of
the
new
sectioning
versus
the
original
report,
the
end
results
appear
to
be
the
same.
Table
2b.
Lindane
CD
1
Mouse
Study
Female
Lung
Alveolar
Bronchiolar
Tumor
Rates
+
[Additional
Histopathology
PLUS
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
5
Original
Diagnoses]
and
Exact
Trend
Test
and
Fisher's
Exact
Test
Results
(p
values)
Results
of
Re
sectioning
(Brunsman,
2001)
Dose
(ppm)
0
10
40
160
Adenomas
5
a
/48
7/
46
7/
47
13/
48
(%)
(10)
(15)
(15)
(27)
p
=
0.0165*
0.3492
0.3644
0.0326*
Carcinomas
1/
48
2
b
/46
2/
47
1/
48
(%)
(2)
(4)
(4)
(2)
p
=
0.4361
0.4839
0.4920
0.7526
Combined
6/
48
8/
46
9/
47
14/
48
(%)
(12)
(17)
(19)
(29)
p
=
0.0235*
0.3535
0.2723
0.0384*
+
Number
of
tumor
bearing
animals/
Number
of
animals
examined,
excluding
those
that
died
before
week
44.
a
First
adenoma
observed
at
week
44,
dose
0
ppm.
b
First
carcinoma
observed
at
week
53,
dose
10
ppm.
Note:
Significance
of
trend
denoted
at
control.
Significance
of
pair
wise
comparison
with
control
denoted
at
dose
level.
If
*
,
then
p
<
0.05.
If
**
,
then
p
<
0.01.
Non
Neoplastic
Lesions
At
78
weeks,
there
were
increases
in
the
incidences
of
centrilobular
hepatocyte
hypertrophy
(control,
6%;
160
ppm,
30%;
p<
0.
01)
and
eosinophilic
focus/
foci
of
hepatocellular
alteration
(control,
4%;
160
ppm,
16%;
p<
0.05)
in
high
dose
males
compared
to
the
control
group
(Table
3).
No
microscopic
liver
changes
were
seen
in
females
Table
3.
Non
Neoplastic
Lesions
in
CD
1
Mice
Fed
Lindane
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
6
Dose
(ppm)
0
10
40
160
0
10
40
160
mg/
kg/
day
0
1.
3
5.2
20.5
0
1.8
7.
1
26.8
males
females
centrilobular
hepatocyte
hypertrophy
3/
50
2/
50
7/
50
15/
50
0/
50
0/
50
0/
50
0/
50
eosinophilic
focus/
foci
of
hepatocyte.
alterations
2/
50
1/
50
5/
50
8/
50
0/
50
0/
50
0/
50
0/
50
lung
epithelial
hyperplasia
1/
50
1/
50
1/
50
2/
50
1/
50
0/
50
0/
50
2/
50
lung
congestion
16/
50
12/
50
16/
50
11/
50
6/
50
13/
50
8/
50
13/
50
Thyroid
dilated
follicles
9/
49
4/
16
3/
16
14/
50
2/
50
1/
19
0/
17
3/
50
LN
Bronchial
increased
cellularity
1/
16
0/
17
1/
15
0/
11
0/
12
1/
15
2/
15
3/
14
Adequacy
of
the
Dosing
for
Assessment
of
Carcinogenicity
There
was
no
significant
change
in
body
weight
and
the
survival
analyses
indicated
no
statistically
significant
incremental
changes
with
increasing
doses
of
lindane
in
male
or
female
mice
(Brunsman,
2001).
All
dose
groups
and
controls
had
68%
survival
at
study
termination.
Histopathologyrevealed
an
increased
incidence
of
liver
lesions
in
male
mice.
The
LOAEL
was
160
ppmfor
males
(20.5
mg/
kg/
day)
and
females
(26.8
mg/
kg/
day)
based
on
liver
hypertrophy
in
males
and
a
slight
increase
in
bronchiolar
alveolar
adenomas
in
females.
The
doses
selected
for
the
above
chronic/
carcinogenicity
study
were
based
on
the
results
of
a
range
finding
subchronic
toxicity
study
(MRID
45424301).
In
this
study,
lindane
(99.78%
a.
i.)
was
administered
to
10
CD
1
mice/
sex/
dose
at
dietary
levels
of
0,
40,
80,
160,
320
ppm
(0,
5.
7,
12.2,
22.8
and
46.2
and
0,
8.9,
16.0,
32.9,
and
62.6
mg/
kg/
day
in
males
and
females,
respectively).
Body
weight
gain
was
reduced
by
27%
in
males
and
9%
in
females
at
the
highest
dose.
The
four
females
in
the
highest
dose
(320
ppm)
group
that
died
during
treatment
period
had
hepatocellular
hypertrophy
and
karyomegaly
in
the
liver
and
Clara
cell
hypertrophy
as
well
as
congestion
in
the
lungs.
These
findings
were
also
seen
in
treated
animals
in
the
160
and
320
ppm
dose
groups
that
were
sacrificed
at
study
termination;
therefore,
these
deaths
were
considered
to
be
treatment
related.
The
early
deaths
in
the
320
ppmdose
group
indicate
that
this
dose
was
excessive.
Based
on
the
results
of
this
study
the
majority
of
the
CARC
concluded
that
the
dose
levels
of
0,
10,
40
160
ppm
selected
for
the
two
year
carcinogenicity
study
in
mice
appeared
to
be
adequate.
However,
a
few
members
felt
that
the
animals
could
have
tolerated
a
higher
dose,
based
on
the
results
of
chronic
study.
2.
Combined
Chronic
Toxicity/
Carcinogenicity
Study
with
Lindane
in
Agouti,
Pseudoagouti
and
Black
Mice
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
7
Reference:
Wolff,
G.
L.
et
al.
Tumorigenic
responses
to
lindane
in
mice:
potentiation
by
a
dominant
mutation,
NCTR,
Jefferson,
AR
;
Carcinogenesis
8(
12):
1889
97
(1987).
Experimental
Design
In
an
NCI
study,
three
strains
of
female
mice,
Agouti,
Pseudoagouti,
and
Black,
were
administered
lindane
at
dietary
concentrations
of
0
or
160
ppm.
Groups
of
36
96
animals
per
strain
were
continuously
fed
treated
or
control
diets
for
up
to
24
months.
Additional
groups
of
48
96
Agouti
and
Black
mice
were
fed
treated
or
control
diets
for
6
months
and
then
fed
control
diet
for
6
or
18
months
(recovery).
Tumor
Analysis:
No
evidence
for
an
increased
incidence
or
a
decreased
latency
of
liver
tumors
was
observed
for
the
black
strain
at
any
time
during
the
24
months
of
study
or
for
the
Pseudoagouti
strain
through
the
18
month
sacrifice.
At
18
months,
0/
34
control
and
12/
36
(33%)
of
the
treated
Agouti
mice
developed
hepatocellular
adenomas;
one
carcinoma
each
in
the
treated
and
control
groups
was
noted.
Both
the
treated
Agouti
and
Pseudoagouti
strains
had
clear
increases
in
adenomas
and
slight
increases
in
carcinomas
at
24
months.
The
incidence
rates
for
the
control
and
treated
Agouti
groups
were
9%
and
35%,
respectively,
for
adenomas
and
13%
and
17%,
respectively,
for
carcinomas.
The
incidence
rates
for
the
control
and
treated
Pseudoagouti
groups
were
5%
and
12%,
respectively,
for
adenomas
and
2%
and
5%,
respectively,
for
carcinomas.
Increases
in
Clara
cell
hyperplasia
were
noted
in
the
lung
at
all
sacrifice
intervals
for
each
strain
and
the
incidence
of
lung
tumors
was
increased
in
later
months
for
the
Agouti
and
Pseudoagouti
strains.
The
percentage
of
mice
with
Clara
cell
hyperplasia
in
the
control
and
treated
groups
was
6
31%
and
72
92%,
respectively,
for
the
Agouti;
6
17%
and
50
79%,
respectively,
for
the
Pseudoagouti;
and
0
14%
and
56
90%,
respectively,
for
the
Black
strain.
Lung
tumors
for
the
Agouti
strain
occurred
in
0%
of
the
control
and
17%
of
the
treated
animals
at
18
months
and
4%
of
the
control
and
19%
of
the
treat
ed
animals
at
24
months.
Lung
tumors
in
the
Pseudoagouti
strain
occurred
in
6%
of
the
controls
and
14%
of
the
treated
animals
at
24
months.
After
recovery,
the
incidences
of
Clara
cell
hyperplasia
(Agouti
and
Black
mice)
and
lung
tumors
(Agouti
mice)
remained
slightly
elevated
as
compared
with
the
controls.
Non
neoplastic
lesions:
No
clinical
signs
of
toxicity
and
no
survival
information
were
reported.
No
apparent
effects
on
body
weights
or
food
consumption
were
observed,
but
only
limited
data
were
presented.
When
compared
with
untreated
controls
at
6
and
12
months,
benzo(
a)
pyrene
monooxygenase
activity
in
the
liver
was
increased
1.61
1.84x
in
the
Agouti,
2.71
2.78x
in
the
Pseudoagouti,
and
2.
07
2.09x
in
the
Black
strains.
Liver
weights
were
increased
14.7
31.2%
in
the
Agouti,
13.5
22.0%
in
the
Pseudoagouti,
and
12.2
16.4%
in
the
Black
strains
at
sacrifice
intervals
up
to
24
months.
Following
the
recovery
period,
liver
weights
of
the
treated
mice
were
similar
to
the
controls.
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
8
Adequacy
of
the
dose:
Only
two
dose
groups
were
tested
in
this
study,
0
and
160
ppm.
The
CARC
concluded
that
although
the
liver
effects
appear
to
suggest
that
a
dose
of
160
ppm
was
adequate,
additional
dose
groups
may
have
provided
confirmatory
information.
Amore
thorough
reporting
of
the
clinical
signs
would
have
been
useful
in
definitive
determination
of
adequacy
of
dose.
3.
NTP
Combined
Chronic
Toxicity/
Carcinogenicity
Study
with
Lindane
in
Mice
Reference:
NCI,
Carcinogenesis
Program,
Bethesda,
MD;
DHEWPub
#
(NIH)
77
814,
1977.
Experimental
Design:
Groups
of
50
B6C3F1
mice/
sex
were
administered
lindane
at
dietary
concentrations
of
80
or
160
ppm
for
80
weeks
then
observed
for
an
additional
10
11
weeks.
Matched
controls
consisted
of
10
mice/
sex.
For
statistical
analysis,
40
untreated
mice/
sex
were
pooled
fromfour
other
bioassays
of
other
test
chemicals.
Discussion
of
tumor
data:
The
incidence
of
hepatocellular
carcinoma
in
low
dose
males
(19/
49)
was
increased
significantly
(p=
0.001)
when
compared
with
pooled
controls
(5/
49).
The
incidence
of
hepatocellular
carcinoma
in
high
dose
male
mice
(9/
46)
was
not
significantly
different
than
the
matched
(2/
10)
or
pooled
controls.
Non
neoplastic
lesions
The
non
neoplastic
lesions
are
presented
in
Table
4
below.
There
were
only
slight
increases
in
liver
inflammation
in
males
and
spleen
hyperplasia
in
females.
Higher
incidences
of
microscopic
changes
in
the
uterus
and
ovaries
of
treated
mice
were
noted;
however,
no
clear
dose
response
was
found.
Table
4.
Non
neoplastic
lesions
in
B6C3F1
male
and
female
mice
Dose
0
80
160
0
80
160
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
9
males
females
liver,
inflammation/
swelling
0/
10
0/
49
5/
46
0/
10
0/
47
0/
46
spleen,
hyperplasia
0/
10
1/
50
0/
47
0/
8
2/
49
4/
48
uterus,
hyperplasia
N/
A
0/
7
3/
44
4/
43
ovary
,
inflamation
3/
7
14/
42
10/
46
Adequacy
of
Dosing
for
Assessment
of
Carcinogenicity
Body
weight
was
unaffected
by
the
test
material.
No
food
or
water
consumption
data
was
provided.
The
CARC
concluded
that
the
use
of
pooled
controls
compromised
the
usefulness
of
the
study
and
the
available
data
were
inadequate
to
make
an
assessment
of
the
carcinogenic
potential
of
lindane.
Table
5
provides
a
comparison
of
other
available
mouse
studies
and
their
deficiencies.
Table
5.
Mouse
Carcinogenicity
Studies,
their
Results
and
Deficiencies
1
Study
design/
deficiencies/
classification
Results
1.
Carcinogenicity
CF
1
mouse
Walker
and
Thorpe
as
published
in
Food
Cosmetic
Toxicology
11:
433
442,1973.
Supplementary.
Data
in
summary
tables
were
not
supported
by
individual
animal
data.
Test
material
cannot
be
validated.
Only
one
dose
level
which
produced
severe
toxicity
was
used.
Study
was
run
concurrently
with
dieldrin,
DDT,
phenobarbitone
Considered
positive
for
liver
tumors.
Males
Females
Control(
45)
BHC(
29)
Control(
44)
BHC(
29)
Adenoma
20%
38%
23%
34%
Carcinoma
4%
55%
0
34%
Total
24%
93%**
23%
69%**
[data
are
%
of
animals
with
tumor,
the
number
in(
)
is
the
number
of
mice
per
sex
examined.]
**
P
<
0.01
study
author's
statistics.
CFl
strain
mouse,
Dose
levels
tested:
0,
400
ppm
and
beta
BHC
for
105
to
109
weeks.
2.
Carcinogenicit
dd
mouse
Hamada,
Yutani
and
Miya
as
published
in
GANN
64:
511
3(
1973).
Supplementary.
Data
were
available
in
summary
form
only.
Very
small
number
(only
3
or
4)
of
animals
were
dosed
per
group.
The
survival
was
poor
and
dosing
period
was
only
32
weeks
.
Test
material
cannot
be
validated.
Study
was
run
concurrently
with
alpha,
beta
and
gamma
isomers
of
BHC.
considered
positive
Three
of
f
our
males
and
one
of
three
f
emales
receiving
pure
gamma
isomer
at
600
ppm
were
said
to
develop
"hepatoma"
or
liver
tumors.
None
of
the
controls
or
mice
dosed
with
100
or
300
ppm
developed
these
tumors.
dd
strain
mice,
dose
levels
0,
100,
300
or
600
ppm
of
gamma,
alpha
or
beta
hexachlorocyclohexane
or
crude
"BHC"
for
36
to
38
weeks.
3.
Oncogenicity
B6C3F1
mouse
NCI,
No.:
NCI
CG
TR
14,
1977
Supplementary:
Use
of
only
10
mice
per
sex
for
the
control
group
compromised
the
usef
ulness
of
the
study.
Data
were
in
summary
tables
only.
There
were
no
indications
of
toxicity
at
high
dose.
Test
material
cannot
be
validated.
Considered
positive
at
low
dose
only.
Hepatocellular
Carcinomas
Dose
Level
Males
Females
Control
10
2(
20%)
10
0
80
ppm
49
19(
39%)
47
2(
4%)
160
ppm
46
9(
20%)
46
4(
7%)
NCI
study
conclusion
is
that
the
chemical
is
not
positive
for
liver
tumors.
Conclusion
corroborated
by
Vesselinovich
and
Carlborg.
The
CAG
of
ORD
considers
low
dose
group
positive.
Dose
levels
tested
were
0,
80
and
160
ppm
for
80
weeks
with
10
weeks
recovery.
B6C3CF
1
strain
mice.
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
10
4.
Oncogenicity
Chbb
NMRI
mouse
Boehringer
Sohn
Ingelheim
am
Rhein,
No
Study
No.:
February
25.
1975
Supplementary:
Insufficient
raw
data
were
used
to
support
conclusions.
There
was
no
verif
ication
of
identity
of
test
material
and
no
evidence
of
toxicity
at
high
dose
level.
No
evidence
of
liver
neoplasms.
Dose
levels
tested
0,
12.5,
25
and
50
ppm.
Chbb
NMRI
strain
mice.
5.
Oncogenicity
mice
(strain
unspecified)
Ito
,
Nagasaki,
Arie,
Sughara
and
Makiura,
Nara
Medical
University
No
Study
No.:
as
published
in
J.
National
Cancer
Institute
51:
817
826,
1972
.
Supplementary/
Invalid:
No
individual
animal
data
were
provided,
test
was
conducted
for
only
24
weeks.
There
was
no
verif
ication
of
the
test
material.
gamma
isomer
was
not
shown
to
increase
liver
tumors.
Alpha
isomer
was
positive.
Dose
levels
tested
0,
100,
250
or
500
ppm
for
24
weeks.
Strain
was
not
specified.
6.
oncogenicity
ICR
JCL
mouse
Goto,
Hattori,
Miyagawa
and
Enomoto,
Gakushin
University,
as
published
in
Chemosphere
1(
6):
279
282
1972.
No
Study
No.,
Supplementary:
No
individual
animal
data
were
available
and
there
was
no
verif
ication
of
the
test
material.
Single
dose
level
f
or
only
26
weeks.
Other
isomers
were
tested
at
the
same
time.
No
inf
ormation
on
survival
or
reactions
to
treatment
was
available.
Test
material
was
not
validated
as
lindane.
considered
positive
Liver
tumors
developed
in
5
of
10
mice
dosed
with
gamma
isomer
after
26
weeks.
Dose
level
tested:
0
and
600
ppm,
other
isomers
of
HCH
also
tested.
ICR
JCL
strain
mouse.
7.
Carcinogenicit
dd
mouse
Nagasaki,
Tonrii,
Mega,
Marugami
and
Ito,
Nara
Medical
University,
as
published
in
Topics
in
Chemical
Carcinogenesis,
1972
No
Study
No.:
Supplementary:
Technical
ECCE
(mixture
of
isomers)
was
used,
not
lindane.
Data
were
available
in
summary
tables
only.
Only
males
were
tested.
"Hepatoma"
resulted
in
response
to
660
ppm
of
the
test
material
(mixture
of
isomers).
Doselevelstested:
0,
6.
6,
66and660ppm.
dd
strain
of
mice,
only
males
tested.
8.
Carcinogenicity
mouse
Wolff
and
colleagues.
AS
published
in
Carcinogenesis
8(
12):
1889
1892
,
1987
Supplementary:
Data
are
in
summary
tables
only.
No
verif
ication
of
the
test
material.
Only
f
emales
tested.
Only
a
single
dose
tested.
No
data
on
clinical
observations,
body
weight
or
survival.
This
strain
may
metabolize
lindane
at
a
slower
rate
with
resulting
accumulation
in
tissue.
Considered
positive
in
two
of
three
strains
Liver
and
lung
adenomas
and
liver
carcinomas
in
"pseudoagouti"
and
"yellow"
but
not
in
black
normal
mice.
Dose
levels
tested
0
and
160
ppm.
Strains
as
indicated
above.
1
This
table
developed
by
John
Doherty
(1993
RfD
document)
has
been
slightly
modified.
5.
Carcinogenicity
Study
in
Rats
Reference:
Aymes,
S.
J.
1993.
Lindane:
Combined
carcinogenicity
and
toxicity
study
by
dietary
administration
to
Wistar
rats
for
104
weeks.
Addendum
to
final
report
(Adrenal
histopathology
additional
investigations).
Life
Sciences
Research,
England.
Study
No.
90/
CIL002/
0839.
June
2,
1993.
MRID
42891201.
Unpublished.
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
11
Aymes,
S.
J.
1989.
Combined
carcinogenicity
and
toxicity
study
by
dietary
administration
to
Wistar
rats
for
104
weeks.
Life
Sciences
Research,
England.
Study
No.
90/
CIL002/
0839.
November
7,
1989.
MRID
41853701.
Unpublished.
Aymes,
S.
J.
1989.
Lindane:
Combined
carcinogenicity
and
toxicity
study
by
dietary
administration
to
Wistar
rats
for
104
weeks
Interim
report
week
0
26.
Life
Sciences
Research,
England.
Study
No.
88/
CIL002/
816.
March
7,
1989.
MRID
41094101.
Unpublished.
Experimental
Design
Lindane
(99.75%
a.
i.,
Lot
no.
DA433)
was
administered
in
the
diet
to
groups
of
50
male
and
50
female
Wistar
rats
at
concentrations
of
0,
1,
10,
100,
or
400
ppm
for
2
years.
Corresponding
delivered
doses
were
0,
0.
05,
0.47,
4.81,
and
19.66
mg/
kg/
day,
respectively,
for
males
and
0,
0.06,
0.59,
6.00,
and
24.34
mg/
kg/
day,
respectively,
for
females.
An
additional
15
rats/
sex/
group
were
designated
for
interim
sacrifices
at
30
days
and
26
weeks.
Discussion
of
Tumor
Data
Male
rats
were
identified
as
having
adrenal
pheochromocytomas
(Table
6).
The
percentages
of
animals
with
adrenal
tumors
in
the
0,
1,
10,
100,
and
400
ppm
groups
were
14,
16,
16,
6,
and
24%
for
benign
tumors,
respectively,
and
0,
0,
6,
8,
and
2%
for
malignant
tumors,
respectively.
Statistical
significance
was
not
reached
by
relevant
tests.
When
compared
to
historical
controls,
the
incidence
of
adrenal
pheochromocytomas
in
the
current
study
slightly
exceeded
that
of
the
historical
control
at
the
HDT
(400
ppm).
The
range
of
adrenal
pheochromocytomas
observed
in
the
historical
control
data
was
4/
50
to
11/
50
(8%
22%)
for
male
rats
examined
in
four
studies
conducted
in
1990.
Of
the
18
studies
in
the
historical
control
data,
6
were
performed
in
1990;
the
other
12
were
performed
between
1986
and
1988.
Non
Neoplastic
Lesions
The
incidence
rate
of
periacinar
hepatocytic
hypertrophy
was
significantly
(p<
0.01)
increased
in
the
100
and
400
ppm
groups
with
25/
50
males
and
19/
50
females
at
100
ppm
and
in
40/
50
males
and
43/
50
females
at
400
ppmcompared
with
the
vehicle
control.
No
treatment
related
histopathological
lesions
were
observed
in
the
spleen
or
bone
marrow.
Kidney
lesions
in
males
indicative
of
alpha
2µ
globulin
accumulation
were
observed
in
animals
treated
with
10
ppm;
but
since
this
effect
is
species
(rat)
specific,
it
was
not
considered
relevant
to
human
health
risk
assessment.
Table
6.
Percentage
(%)
of
animals
with
adrenal
pheochromocytomas
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
12
Control
(ppm)
Benign
Malignant
Both
(B
&
M)
0
14014
1
16016
10
16
6
18
100
6
8
14
400
24
2
26
Adjusted
Rates
1
0
29029
1
39039
10
33.5
15.2
38.6
100
12.1
21.4
31.0
400
52.9
2.
9
54.2
Historical
controls:
Benign
8
to
22%
and
Malignant
0
to
2%
1
Kaplan
Meier
estimated
tumor
incidence
at
the
end
of
the
study
after
adjusting
for
inter
current
mortality.
Adequacy
of
Dosing
for
Assessment
of
Carcinogenicity
CARC
concluded
that
the
doses
tested
were
considered
to
be
adequate
and
not
excessive
in
both
sexes.
This
was
based
on
decreased
survival,
decreased
body
weight
gains,
decreased
food
consumption,
and
increased
spleen
and
liver
weights
correlated
with
periacinar
hepatocyte
hypertrophy
in
both
sexes
at
the
high
dose,
relative
to
the
controls.
Final
body
weights
of
the
high
dose
males
were
significantly
(
14%;
p
0.05)
less
than
the
controls.
Body
weights
and
body
weight
gains
for
the
treated
females
were
similar
to
the
controls
throughout
the
study.
Total
food
consumption
for
the
entire
study
was
similar
to
the
control
levels.
Platelet
counts
were
significantly
increased
in
males
at
100
and
400
ppm
at
week
12
and
in
males
and
females
at
week
24,
but
not
at
later
time
points.
High
dose
males
and
females
had
significant
decreases
in
red
blood
cell
parameters
at
week
104
as
compared
with
the
controls.
Significant
changes
in
clinical
chemistry
parameters
were
observed
in
high
dose
males
and
females
during
the
first
year
of
the
study.
Inorganic
phosphorous
and
calcium
were
increased
in
males
and
females;
the
cholesterol
and
urea
were
increased
in
females;
and
the
albumin/
globulin
ratio
was
decreased
in
females.
All
parameters
were
similar
to
the
control
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
13
levels
by
week
104.
High
dose
males
and
females
had
increased
absolute
and
relative
liver
weights
at
all
interim
sacrifices,
although
statistical
significance
was
not
always
reached.
At
study
termination,
absolute
and
relative
liver
weights
were
significantly
increased
in
high
dose
males
and
females.
At
100
ppm,
absolute
and
relative
liver
weights
were
increased
for
both
sexes.
6.
NTP
Combined
Chronic
Toxicity/
Carcinogenicity
Study
with
Lindane
in
Rats
Reference:
NCI,
Carcinogenesis
Program,
Bethesda,
MD;
DHEWPub
#
(NIH)
77
814,
1977.
Experimental
design:
Lindane
was
administered
in
the
diet
of
50
Osborne
Mendel
rats/
sex/
dose
for
a
total
of
80
weeks.
Males
received
320
or
640
ppm
for
38
weeks
and
160
or
320
ppm
for
the
remaining
42
weeks.
Females
received
320
or
640
ppm
for
2
weeks
and
160
or
320
ppm
for
49
weeks;
then
for
the
remaining
29
weeks,
the
dose
was
lowered
to
80
or
160
ppm.
After
the
initial
80
week
treatment
period,
all
animals
were
observed
for
an
additional
29
30
weeks.
Matched
controls
consisted
of
10
rats/
sex.
For
statistical
analysis
45
untreated
rats/
sex
were
pooled
from
four
other
bioassays
of
other
test
chemicals.
Discussion
of
tumor
data
As
shown
in
Table
7,
there
were
three
incidences
of
spleen
hemangioma
in
the
high
dose
male
group
only
and
none
in
the
females.
There
were
also
increases
in
neoplastic
lesions
of
the
liver;
however,
these
were
within
the
historical
control
values
in
this
tumor
for
this
rat
strain
(0
12%,
Goodman
et
al.
2000,
personal
communication).
Other
organs
affected
with
primary
tumors
include:
thyroid,
pituitary,
and
mammary
glands
wit
h
only
a
few
incidences
and
no
clear
dose
response
correlation.
.
Non
neoplastic
Lesions
Microscopic
changes
were
seen
in
the
liver
of
both
males
and
females,
including
cirrhosis,
degeneration
and
necrosis
in
a
dose
dependent
manner.
Cysts,
hyperplasia
and
atrophy
were
seen
in
the
endocrine
and
reproductive
organs
of
these
animals.
Table
7.
Tumor
data
for
Osborne
Mendel
rats
fed
lindane
for
80
weeks
Dose
control
low
high
control
low
high
males
females
spleen
hemangioma
0/
8
0/
44
3/
44
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
14
thyroid,
adenoma
carcinoma
1/
6
5/
37
0/
37
0/
8
1/
44
1/
42
0/
6
1/
37
4/
37
0/
8
1/
44
0/
42
liver,
neoplastic
nodule
0/
10
3/
45
2/
45
0/
10
4/
48
2/
45
pituitary,
adenoma
carcinoma
0/
10
0/
32
2/
35
0/
7
0/
45
2/
41
0/
10
1/
32
0/
35
0/
7
1/
45
0/
41
mammary,
adenoma
carcinoma
0/
10
0/
48
2/
49
0/
10
3/
50
1/
50
0/
10
1/
48
0/
49
1/
10
1/
50
0/
50
Adequacy
of
Dosing
for
Assessment
of
Carcinogenicity
Mean
body
weight
did
not
show
consistent
changes
from
the
administration
of
lindane.
The
CARC
concluded
that
the
use
of
pooled
controls
compromised
the
usefulness
of
the
study
and
the
available
data
were
inadequate
to
make
an
assessment
of
the
carcinogenic
potential
of
lindane.
IV.
TOXICOLOGY
1.
Metabolism
Lindane
is
distributed
to
all
organs
at
measurable
concentrations
within
a
few
hours
after
oral
administration.
The
highest
concentrations
are
found
in
adipose
tissue.
The
metabolism
of
lindane
is
initiated
through
one
of
the
following
pathways:
dehydrogenation
leading
to
HCH,
dehydrochlorination
leading
to
formation
of
PCCH,
dechlorination
leading
to
formation
of
tetrachlorohexene,
or
hydroxylation
leading
to
formation
of
hexachlorocyclohexanol.
Further
metabolism
leads
to
a
large
number
of
metabolites.
Volatilizalion
appears
to
be
an
important
route
of
its
dissipation
under
the
high
temperature
conditions
oftropicalregions.
Lindane
is
converted
byenzymatic
reactions,
mainlyin
the
liver.
In
mammals,
including
humans,
lindane
is
excreted
very
rapidly
in
urine
and
feces
after
metabolic
degradation;
only
small
amounts
are
eliminated
unchanged.
The
half
life
of
lindane
administered
to
rats
is
2
4
days
depending
on
the
frequency
of
exposures,
single
or
repeated.
Other
metabolites
are
also
known
to
be
associated
with
lindane
exposure;
these
include
2,4,6
trichlorophenol
and
2,
4,
5
trichlorophenol.
Exposure
to
lindane
in
a
residential
setting
is
expected
to
be
negligible
except
for
use
as
a
lice
or
scabies
treatment.
These
uses
are
regulated
by
FDA
and
have
not
been
evaluated
in
this
document.
2.
Mutagenicity
As
part
of
the
Registration
Standard
prepared
in
1985,
the
available
literature
and
submitted
mutagenicity
studies
were
evaluated
(HED
Document
No.
004704).
Based
on
this
evaluation,
it
was
concluded
that
the
weight
of
the
evidence
with
conventional
genotoxicity
testing
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
15
indicated
that
lindane
did
not
interact
with
DNA
or
interfere
with
genetic
mechanisms.
This
position
was
reiterated
in
1993
(memo
by
G.
Ghali,
1993).
Reviews
prepared
by
IARC
(1979/
1987),
IPCS
(1990)
and
ATSDR(
1999)
indicate
that
lindane
and
its
associated
isomers
have
mixed
genotoxic
potential.
In
addition,
numerous
mutagenicity
studies
have
been
evaluated
by
the
European
Commission
(EU)
in
their
draft
monograph
on
lindane
(2001).
Representative
studies
were
selected
from
the
EU
evaluation
of
lindane
since
they
were
performed
according
to
OECD
or
EPA
guidelines.
These
include:
1.
A
bacterial
mutagenicity
assay
using
Salmonella
typhimurium
with
and
without
metabolic
activation
which
was
negative
up
to
cytotoxic
doses
(5000
ug/
plate
+S9)
or
insoluble
doses
(greater
than
or
equal
to
500
ug/
plate
S9;
greater
than
or
equal
to1500
ug/
plate
+S9
;
Oesch,
1980).
2.
An
aerobic
mammalian
cell
(V79)
gene
mutation
assay
was
negative
up
to
cytotoxic
doses
(greater
than
or
equal
to
50
ug/
mL
S9;
greater
than
or
equal
to
250
ug/
mL+
S9);
the
compound
precipitated
at
greater
than
or
equal
to
250
ug/
mL
(Glatt,
1984).
EPA
only
received
an
anaerobic
assay
which
had
an
acceptable
aerobic
portion
(Glatt,
1985).
3.
Mammalian
cell
cytogenetic
assay
was
negative
in
CHO
cells
up
to
cytotoxic
doses
(greater
than
or
equal
to
33.2
ug/
mL
S9;
greater
than
33.2
ug/
mL+
S9).
(Murli,
1990).
4.
UDS
in
primary
rat
hepatocytes
was
also
found
to
be
negative
up
to
cytotoxic
doses
(15
ug/
mL)
(Cifone,
1990).
There
are
no
acceptable
in
vivo
studies
but
they
are
not
necessary
to
satisfy
pre
1991
FIFRA
guideline
requirements.
Newer
published
data
shows
that
lindane
induces
oxidative
stress
in
the
liver
of
treated
rats
(Carrion
et
al.,
2001;
Cornnejo
et
al.,
2001;
Videla
et
al.,
2000).
In
agreement
with
these
findings,
the
1999
ATSDR
review
states
that
oxidative
stress
may
be
a
possible
mechanism
of
liver
toxicity.
The
CARC
has
an
additional
concern
related
to
possible
genetic
effects
on
germinal
cells.
Although
an
old
submitted
dominant
lethal
assay
(MRID
00062657)
was
negative,
it
was
considered
unacceptable
and
not
upgradable
because
of
technical
deficiencies.
Recent
information
found
in
the
open
literature
indicates
that
topical
application
of
lindane
led
to
rapid
absorption
and
accumulation
in
rat
testes
(Suwalsky
et
al.,
2000).
The
investigators
reported
widespread
damage
to
a
"great
number"
of
Leydig
cells
after
the
application
of
1%
lindane
once
daily
for
4
consecutive
days.
These
findings
are
consistent
with
the
work
of
Walsh
and
Stocco
(2000)
showing
inhibition
of
steroidogenesis
by
reductions
in
steroidogenic
acute
regulatory
(StAR)
protein
expression
in
mouse
Leydig
cells
in
vitro.
Since
there
is
some
evidence
that
lindane
reaches
and
damages
germ
cells,
the
Committee
recommends
that
the
dominant
lethal
assay
be
repeated
to
determine
if
there
is
a
genetic
component
to
the
reproductive
(germ
cell)
effects
reported
above
for
lindane.
3.
Structure
Activity
Relationship
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
16
Technical
grade
hexachlorohexane
(HCH)
which
consists
of
alpha,
beta,
gamma,
delta
and
epsilon
isomers
of
HCH
is
a
carcinogen.
In
rodents
studies,
the
pure
alpha
isomer
of
HCH
has
been
found
to
induce
liver
tumors;
this
is
also
true
for
the
pure
beta
isomer
of
HCH..
These
studies
are
found
in
the
NTP,
IARC
and
IPCS
reports
on
hexachlorohexanes.
Lindane
shares
its
structure
with
at
least
four
other
isomers.
They
differ
only
with
respect
to
the
position
of
the
chlorine
atoms
in
the
alpha
or
beta
positions,
above
or
below
the
plane
of
the
hexane
ring
structure.
Structure
of
HCH
(Lindane)::
isomer:
1
2
3
4 ,
5 ,
6
hexachlorocyclohexane
Other
isomers:
isomer:
1
2
3
4 ,
5 ,
6
hexachlorocyclohexane
isomer:
1
2
3
4 ,
5 ,
6
hexachlorocyclohexane
isomer:
1
2
3
4 ,
5 ,
6
hexachlorocyclohexane
isomer:
1
2
3
4 ,
5 ,
6
hexachlorocyclohexane
Isomers
of
hexachlorocyclohexane
(HCH),
other
than
lindane,
have
been
classified
as
follows,
according
to
IRIS:
The
technical
HCH
and
the
alpha
isomer
are
classified
as
B2,
probable
human
carcinogens.
The
beta
isomer
is
classified
as
C,
possible
human
carcinogen.
The
delta
and
epsilon
isomers
are
classified
as
D,
not
classifiable
as
to
human
carcinogenicity.
Appendix
A
contains
a
summary
of
various
studies
which
examine
the
carcinogenicity
of
the
gamma
isomer
(Lindane)
alone
or
in
comparison
with
the
other
isomers.
4.
Subchronic,
and
Chronic
Toxicity
Subchronic
Toxicity
Mice
A
range
finding
subchronic
toxicity
study
(MRID
45424301)
was
conducted
to
determine
the
doses
to
be
used
in
a
two
year
carcinogenicity
study.
In
this
study,
Lindane
(99.
78%
a.
i.)
was
administered
to
10
CD
1
mice/
sex/
dose
in
the
diet
at
dose
levels
of
0,
40,
80,
160,
320
ppm
(0,
5.
7,
12.2,
22.8
and
46.2
and
0,
8.9,
16.0,
32.9,
and
62.6
mg/
kg/
day
in
males
and
females,
respectively).
No
treatment
related
clinical
signs
were
observed.
Five
females
died
or
were
killed
during
the
treatment
period.
Four
were
in
the
highest
dose
(320
ppm)
group
and
one
from
the
control
group
was
a
humane
kill.
These
animals
presented
wit
h
no
macroscopic
changes.
Histopathology
revealed
hepatocyte
hypertrophy
and
karyomegaly
in
the
liver
and
Clara
cell
hypertrophy
and
congestion
in
the
lungs.
These
findings
were
also
seen
in
treated
animals
in
the
160
and
320
ppm
dose
groups
that
were
sacrificed
at
study
termination;
therefore,
these
deaths
were
considered
to
be
treatment
related.
Body
weight
was
reduced
by
6%
in
males
and
was
unaffected
in
females
in
the
highest
dose
tested
(320
ppm).
Body
weight
gain
was
reduced
by
27%
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
17
in
males
and
9%
in
females.
In
a
subchronic
inhalation
toxicity
study,
Lindane
(99.6%
a.
i.,
Batch
no.
DA433)
was
administered
by
inhalation
to
groups
of
45
male
and
45
female
CD
1
mice
at
nominal
concentrations
of
0,
0.3,
1.0,
5.0
to
10
mg/
m3
(0,
0.
1,
0.
4,
2.
0
or
4.0
mg/
kg/
6
hrs),
for
14
weeks.
Exposures
were
6
hours/
day,
5
day/
week
as
described
in
the
pilot
study.
During
the
first
five
exposures,
the
high
dose
group
was
exposed
to
a
mean
concentration
of
9.
72
mg/
m3
(4.
0
mg/
kg/
6
hrs),
but
due
to
excessive
deaths,
the
mean
concentration
was
lowered
to
4.
94
mg/
m3
(2.
0
mg/
kg/
6
hrs).
No
exposure
related
effects
were
noted
for
body
weight
gain,
food
consumption,
water
consumption,
or
ophthalmoscopic,
hematology,
clinical
chemist
ry,
or
urinalysis
parameters.
Bone
marrow
analysis
did
not
show
any
time
or
concentration
related
changes.
Brain,
kidney,
lung,
spleen,
thymus,
and
adrenal,
and
testes
weights
were
similar
between
the
treated
and
control
animals.
Liver
weights
of
females
exposed
to
5
mg/
m3
were
increased
14%
(p
0.05)
at
week
20.
Rats
In
a
subchronic
oral
neurotoxicity
study
(MRID
44781101),
groups
of
10
Crl:
CD®
BR
rats/
sex/
group
were
administered
lindane
(Batch
No.
HLS96/
1,
Purity
99.78%)
in
the
diet
for
13
weeks
at
concentrations
of
0
(control),
20,
100,
or
500
ppm.
Due
to
severe
toxic
reactions
to
treatment
at
500
ppm,
the
dose
was
reduced
to
400
ppm
on
day
11
of
treatment
thereafter.
These
doses
resulted
in
average
daily
intake
values
of
0,
1.4,
7.1,
and
28.
1
mg/
kg/
day
for
males
and
0,
1.6,
7.9,
and
30.2
mg/
kg/
day
in
females
for
0,
20,
100,
and
500/
400
ppm,
respectively.
Significant
treatment
related
decreases
(p<
0.05
or
p<
0.01)
in
body
weight
were
observed
among
males
and
females
treated
with
500/
400
ppm
of
14%
and
23%,
respectively.
Decreases
in
body
weight
gains
(70%
and
180%
,p<
0.
01),
food
consumption
(35%
and
50%
,
p<
0.05
or
p<
0.01,
respectively),
and
food
conversion
ratios
were
observed
for
males
and
females
in
the
500
ppm
groups
compared
to
the
control
group
for
the
first
week
of
the
study.
Male
rats
tended
to
recover
from
these
effects
after
the
dose
was
lowered.
Females,
however,
did
not
exhibit
this
same
level
of
recovery
as
their
food
consumption
remained
slightly
depressed
throughout
the
remainder
of
the
study.
Females
in
the
100
ppm
group
had
significantly
decreased
body
weight
gains
(40%,
p<
0.05)
compared
to
the
control
group
during
the
first
week
of
the
study
and
this
effect
continued,
although
not
at
a
level
of
significance
throughout
the
remainder
of
the
study.
Females
in
the
100
ppm
group
had
significantly
decreased
food
consumption
(16%,
p<
0.01)
for
the
first
week
of
the
study
and
this
trend
continued
throughout
the
study.
Liver
weights
were
also
found
to
be
increased
at
500/
400
ppm
for
both
sexes;
no
additional
information
was
given.
Chronic
Toxicity
In
the
chronic
toxicity/
carcinogenicity
study
(MRID41853701),
lindane
(99.75%
a.
i.,
Lot
no.
DA433)
was
administered
in
the
diet
to
groups
of
50
male
and
50
female
Wistar
rats
at
concentrations
of
0,
1,
10,
100,
or
400
ppm
for
2
years.
Corresponding
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
18
delivered
doses
were
0,
0.
05,
0.47,
4.81,
and
19.66
mg/
kg/
day,
respectively,
for
males
and
0,
0.
06,
0.59,
6.00,
and
24.34
mg/
kg/
day,
respectively,
for
females.
An
additional
15
rats/
sex/
group
were
designated
for
interim
sacrifices
at
30
days
and
26
weeks.
Body
weights
were
slightly
less
than
the
controls
for
the
high
dose
males
(
6%)
and
females
(
8%)
during
weeks
1
5
of
the
study,
but
gradually
increased
to
within
2%
of
the
control
level
by
week
26
for
males
and
week
9
10
for
females.
High
dose
females
hadsignificantlydecreased
hemoglobin,
decreased
RBCcounts,
and
decreased
PCV.
These
red
cell
parameters
were
"marginally
lower"
for
high
dose
males
(non
statistically
significant).
Platelet
counts
increased
in
mid
and
high
dose
males
and
females.
White
cell
counts
significantly
increased
in
mid
dose
and
in
highdose
females
due
to
increases
in
neutrophils.
The
liver
appears
to
be
the
major
target
organ.
Kidney
lesions
in
male
rats
indicative
of
alpha
2µ
globulin
accumulation
were
observed
in
animals
treated
with
10
ppm,
but
are
not
considered
relevant
to
human
health
risk
assessment.
Absolute
kidney
weights
were
significantly
increased
in
high
dose
males.
Absolute
and
relative
kidney
weights
increased
in
mid
dose
males
and
high
dose
males
and
females.
The
incidence
of
periacinar
hepatocytic
hypertrophy
was
significantly
increased
in
males
at
100
and
400
ppm
and
in
females
at
400
ppm.
This
lesion
was
not
seen
in
control
animals
of
either
sex.
No
treatment
related
histopathological
lesions
were
observed
in
the
spleen,
adrenals,
brain,
or
thymus.
Bone
marrow
data
presentation
was
inadequate
for
assessment.
5.
Mode
of
Action
Studies
No
mode
of
action
studies
have
been
submitted
for
lindane.
There
have
been,
however,
several
published
studies
which
attempt
to
elucidate
the
initiator
promoter
activity
of
lindane.
As
discussed
earlier
lindane
does
not
appear
to
have
a
clear
mutagenic
potential.
Lindane
may
act
as
a
promoter
as
evidenced
by
studies
with
Agouti,
Pseudoagouti
and
Black
mice.
Only
Agouti
and
Pseudoagouti
mice,
which
have
a
transformed
genotype
linked
to
tumorigenicity,
were
found
to
have
an
increased
incidence
of
liver
and
lung
tumors.
The
Black
mice
had
no
tumors
in
the
24
month
period
of
the
study.
The
Pseudoagouti
and
Black
mice
had
a
low
rate
of
spontaneous
tumor
incidence
in
the
liver
and
lung,
but
of
these
two
only
the
Pseudoagouti
responded
to
lindane.
Therefore,
lindane
appears
to
augment
the
propensity
of
these
genetically
altered
mice
to
develop
tumors.
It
has
been
suggested
that
lindane
has
a
similar
mode
of
action
to
phenobarbital,
which
also
increases
the
incidence
of
benign
tumors
in
these
mice.
As
discussed
earlier
on
page
13,
oxidative
stress
may
be
a
possible
mechanism
of
liver
toxicity.
Suggestions
have
been
made
that
the
metabolites
of
lindane
may
contribute
to
its
carcinogenic
potential.
One
major
urinary
metabolite,
2,4,6
TCP,
is
considered
to
be
a
carcinogen.
However
studies
indicate
that
TCP
may
have
only
a
minimal
effect
on
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
19
the
overall
carcinogenic
potential
of
lindane.
V.
COMMITTEE'S
ASSESSMENT
OF
THE
WEIGHT
OF
THE
EVIDENCE
1.
Carcinogenicity
The
CARCconcluded
that
lindane
is
carcinogenic
only
to
female
mice
and
is
not
carcinogenic
to
male
mice
and
male
and
female
rats.
!
CD
1
female
mice
had
significant
increasing
trends
and
significant
differences
in
pair
wise
comparisons
of
the
160
ppm(
26.8
mg/
kg/
day)
dose
group
with
the
controls,
for
lung
alveolar
bronchiolar
adenomas
(23%
vs
6%
in
controls)
and
combined
adenomas/
carcinomas
(25%
vs
8%
in
controls),
all
at
p
<
0.
05;
the
incidence
of
lung
adenomas
(23%)
was
slightly
outside
the
historical
control
range
(6%
19%).
The
increased
incidence
of
carcinomas
was
not
dosedependent
and
tumor
response
was
variable.
Lindane
was
not
carcinogenic
to
male
mice.
No
non
neoplastic
liver
changes
were
seen
in
females.
The
majority
of
the
CARC
considered
the
dosing
to
have
been
adequate
and
not
excessive
based
on
an
increase
in
the
incidence
of
centrilobular
hepatocyte
hypertrophy
as
well
as
eosinophilic
foci
of
hepat
ocellular
alteration
in
high
dose
males
compared
to
the
control
group;
similar
liver
findings
were
also
reported
in
a
range
finding
subchronic
toxicity
study
in
which
early
deaths
of
four
females
were
reported
in
the
320
ppm
dose
group
indicating
that
this
dose
was
excessive.
However,
based
on
the
results
of
the
chronic
study
a
few
members
felt
that
the
animals
could
have
tolerated
a
higher
dose.
!
At
160
ppm,
both
the
treated
female
Agouti
and
Pseudoagouti
mice
had
an
increased
occurrence
of
benign
lung
tumors
(19%
vs
4%
in
controls
and
14%
vs
6%
in
controls,
respectively).
In
addition,
both
the
treated
female
Agouti
and
Pseudoagouti
mice
had
increases
in
liver
adenomas
(35%
vs
9%
in
controls
and
17%
vs
13%
in
controls,
respectively)
and
slight
increases
in
liver
carcinomas
(5%
vs
2%
in
controls
and
12%
vs
5%
in
controls)
at
24
months.
No
statistical
analyses
of
tumor
data
were
provided.
There
was
no
increase
in
incidence
or
decrease
in
latency
period
of
liver
tumors
in
Black
and
Pseudoagouti
strains
of
mice.
There
was
evidence
of
increased
liver
weights
and
increased
incidence
of
Clara
cell
hyperplasia
in
Agouti
and
Black
strains
of
mice.
Increases
in
Clara
cell
hyperplasia
were
noted
in
the
lung
at
all
sacrifice
intervals
for
each
strain
and
the
incidence
of
lung
tumors
was
increased
in
later
months
for
the
female
Agouti
and
Pseudoagouti
mice.
The
percentage
of
mice
with
Clara
cell
hyperplasia
in
the
treated
and
control
groups
was
72%
92%
and
6%
31%,
respectively,
for
the
Agouti;
50%
79%
and
6%
17
respectively,
for
the
Pseudoagouti;
and
56%
90%
and
0%
14%,
respectively,
for
the
female
Black
mice.
However,
the
study
was
conducted
on
few
animals,
only
a
single
dose
was
tested,
no
statistical
analyses
of
tumor
data
were
presented;
and
the
results
of
the
studywere
not
adequately
reported.
The
Committee
concluded
that
although
the
liver
effects
appear
to
suggest
that
a
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
20
dose
of
160
ppm
was
adequate,
additional
dose
groups
could
have
provided
confirmatory
information.
!
The
incidence
of
hepatocellular
carcinoma
in
low
dose
B6C3F1
males
(19/
49)
was
significant
(p=
0.001)
when
compared
with
that
in
pooled
controls
(5/
49).
The
incidence
of
hepatocellular
carcinoma
in
high
dose
male
mice
(9/
46)
was
not
significantly
different
than
the
matched
(2/
10)
or
pooled
controls.
The
CARC
could
not
assess
the
carcinogenicity
of
lindane
in
B6C3F1
male
and
female
mice
because
the
data
reporting
was
inadequate,
there
were
no
indications
of
toxicity
at
the
high
dose
and
the
test
material
could
not
be
validated.
Moreover,
the
use
of
only
10
mice
per
sex
for
the
control
group
compromised
the
usefulness
of
the
study.
The
Committee
concluded
that
the
increased
incidence
of
benign
lung
tumors
in
female
CD
1
mice
was
treatment
related
because
the
treatment
related
statistically
significant
increase
in
lung
adenomas
in
female
CD
1
mice
was
correlated
with
increases
in
lung
tumors
in
two
genetically
susceptible
strains
of
mice
(Agouti
and
Pseudoagouti).
Although
there
is
some
evidence
of
liver
tumor
induction
in
these
genetically
susceptible
strains
of
mice,
there
was
no
evidence
of
liver
tumors
in
CD
1
mice.
Nevertheless,
the
evidence
of
hepatotoxicity
(increased
incidences
of
liver
hypertrophy
and
liver
foci
in
both
sexes)
and
promoting
activity
suggests
the
liver
as
a
major
target
organ
of
toxicity.
!
The
treated
male
Wistar
rats
developed
adrenal
pheochromocytomas.
The
percentages
of
animals
with
adrenal
tumors
in
the
0,
1,
10,
100,
and
400
ppm
groups
were
14%,
16%,
16%,
6%,
and
24%
for
benign
tumors,
respectively,
and
0%,
0%,
6%,
8%,
and
2%
for
malignant
tumors,
respectively.
Statistical
significance
was
not
reached
by
relevant
tests
and
no
dose
response
was
evident.
When
compared
to
historical
controls,
the
incidence
of
adrenal
pheochromocytomas
in
the
current
studyslightlyexceeded
that
of
the
historical
control
at
the
HDT
(400
ppm).
The
range
of
adrenal
pheochromocytomas
observed
in
the
historical
control
data
was
4/
50
to
11/
50
(8%
22%)
for
male
rats
examined
in
four
studies
conducted
in
1990.
Of
the
18
studies
in
the
historical
control
data,
6
were
performed
in
1990;
the
other
12
were
performed
between
1986
and
1988.
The
Committee
concluded
that
the
adrenal
tumors
in
male
rats
were
not
treatment
related.
The
doses
tested
were
considered
to
be
adequate
and
not
excessive
in
both
sexes
based
on
decreased
survival,
decreased
body
weight
gains
and
decreased
food
consumption;
the
increased
spleen
and
liver
weights
correlated
with
increased
occurrence
of
periacinar
hepatocyte
hypertrophy
in
both
sexes
at
the
high
dose.
!
There
were
three
spleen
hemangiomas
in
44
high
dose
male
Osborne
Mendel
rats
only
(0/
8
in
controls)
and
none
in
the
females.
There
were
also
non
dose
related
increases
in
neoplastic
lesions
of
the
liver
(3/
45
and
2/
45
in
males
and
4/
48
and
2/
45
in
females
in
the
low
and
high
dose
groups
compared
to
0/
10/
sex
in
control
groups)
which
were
within
the
historical
control
values
(0%
12%).
Other
organs
with
primary
tumors
include:
thyroid,
pituitary,
and
mammary
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
21
glands
with
only
a
few
incidences
but
there
was
no
clear
dose
response.
Dosing
at
the
highest
level
was
considered
to
be
adequate
based
on
microscopic
changes
seen
in
the
liver
of
both
males
and
females,
including
cirrhosis,
degeneration,
necrosis
in
a
dose
dependent
manner.
Cysts,
hyperplasia
and
atrophy
were
seen
in
the
endocrine
and
reproductive
organs
of
these
animals.
Survival
of
the
animals
was
adequate
for
meaningful
statistical
analyses
of
the
incidence
of
tumors.
The
CARC
concluded
that
lindane
was
not
carcinogenic
to
male
and
female
Wistar
rats
and
that
the
results
of
the
study
in
Osborne
Mendel
rats
were
difficult
to
interpret
and
were
not
useful
in
determining
the
carcinogenic
potential
of
lindane
in
that
strain
of
rat.
2.
Mutagenicity
!
Lindane
has
been
tested
in
a
battery
of
pre
1991
mutagenicity
assays
which
satisfies
the
guideline
requirements.
The
review
of
both
the
guideline
and
literature
studies
suggests
that
lindane
does
not
interact
with
DNAor
interfere
with
genetic
mechanisms.
However,
since
there
is
some
evidence
that
lindane
reaches
and
damages
germ
cells,
the
Committee
recommended
that
the
dominant
lethal
assay
be
repeated
to
determine
if
there
is
a
genetic
component
to
the
reproductive
(germ
cell)
effects
reported
for
lindane.
3.
Structure
Activity
Relationship
!
Isomers
of
hexachlorocyclohexane
(HCH),
other
than
lindane,
have
been
classified
for
carcinogenic
potential.
The
technical
HCH
and
the
alpha
isomer
are
classified
as
B2,
probable
human
carcinogens.
The
beta
isomer
is
classified
as
C,
possible
human
carcinogen.
The
delta
and
epsilon
isomers
are
classified
as
D,
not
classifiable
as
to
human
carcinogenicity.
4.
Mode
of
Action
!
The
tumor
initiating
activity
reported
in
the
literature
has
been
discounted
due
to
the
lack
of
morphologic
alterations
in
liver
foci
after
treatment
with
lindane.
Lindane
appears
to
augment
the
propensity
of
genetically
altered
mice
to
develop
tumors.
However,
no
definitive
studies
have
established
the
mode
of
action
for
liver
tumor
induction
by
lindane.
There
is
a
suggestion
that
oxidative
stress
may
play
a
role
in
the
liver
toxicity
of
lindane.
VI.
CLASSIFICATION
OF
CARCINOGENIC
POTENTIAL
In
accordance
with
the
Agency's
Draft
Guidelines
for
Carcinogen
Risk
Assessment
(July,
1999),
the
Committee
classified
lindane
into
category:
"Suggestive
evidence
of
carcinogenicity,
but
not
sufficient
to
assess
human
carcinogenic
potential"
based
on
the
occurrence
of
benign
lung
tumors
in
one
sex
of
one
species
(i.
e.,
female
CD
1
mice).
LINDANE
CANCER
ASSESSMENT
DOCUMENT
FINAL
REPORT
22
VII.
QUANTIFICATION
OF
CARCINOGENIC
POTENTIAL
The
Committee
recommended
that
quantification
of
human
cancer
risk
is
not
required.
VIII
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FINAL
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APPENDIX
A
Carcinogenicity
Studies
comparing
the
toxicity
of
gamma
HCH
with
other
isomers
Study
#
of
animals
doses
results
for
lindane
(gamma
HCH)
results
for
other
isomers
Carcinogenicityrat
(The
chronic
toxicities
of
technical
benzene
hexachloride
and
its
alpha,
beta
and
gamma
isomers)
published:
1950
10
/10
Wistar
rat
0,
5,
10,
50,
100,
400,
800
or
1600
ppm
of
,
,
or
HCH.
At
100
ppm
of
HCH
,
liver
wt.
incr
no
frank
liver
tumors
induced
by
HCH
26
CarcinogenicityRats
(Pathologic
changes
in
the
liver
of
rats
after
feeding
low
levels
of
various
insecticides)
published:
1957
6
/
6
0,
50,
100
ppm
for
8
months.
One
50
ppm
,
and
one
each
100
ppm
and
developed
centrilobular
hypertrophy,
peripheral
migration
of
basophilic
cytoplasmic
granulations
and
cytoplasmic
inclusion
bodies.
Carcinogenicity
rats
(Brief
communication:
development
of
hepatocellular
carcinomas
in
rats
treated
with
benzene
hexachloride)
published:
1975.
9
groups
of
W
rats
(Japanese
strain)
0,
500,
1000
or
1500
ppm
of
,
,
,
or
BHC
BHC
:
cell
hypertrophy
BHC:
cell
hypertrophy,
nodular
hyperplasia
(27/
41
dosed
w/
1000
ppm
for
48
72
wks),
hepatocellular
carcinoma
(4/
29
dosed
w/
1000
ppm
for
72
wks)
,
,
,
:cell
hypertrophy
Carcinogenicity
rats
(Bioassay
of
lindane
for
possible
carcinogenicity)
NCI
(NCI
RG
TR
14)
1977
10
/10
Osborne
Mendel
rats
50
50
0
ppm;
320
or
640
ppm
for
38
wks,
160
or
320
ppm
for
42
wks,
then
0
ppm
for
30
wks
320
or
640
for
2
wks,
160
or
320
ppm
for
49
wks,
80
or
160
ppm
for
29
wks,
then
0
ppm
for
30
wks.
Incidence
of
liver
neoplasia
is
within
historical
control
levels
Carcinogenicity
mice
(Bioassay
of
lindane
for
possible
carcinogenicity)
NCI
(NCI
RG
TR
14)
1977
10
/10
BGC3F1
hybrid
mice
50
/50
0
ppm
80
or
160
ppm
for
80
wks
then
control
diet
for
10
wks
hepatocellular
carcinoma:
0
ppm
(20%),
80
ppm
(39%),
160
ppm
(20%)
27
Carcinogenicitymouse
(The
toxicology
of
dieldrin
(HEOD).
II.
Comparitive
long
term
oral
toxicity
studies
in
mice
with
dieldrin,
DDT,
phenobarbitone,
beta
BHC
and
gamma
BHC)
Thorpe
and
Walker
(1973).
CF1
mice
45
/45
30
/30
0
ppm
(24/
23%)
400
ppm
(gamma
BHC)
10
ppm
(dieldrin)
100
ppm
(DDT)
500
ppm
(phenobarbitone)
200
ppm
betaBHC
/
%
of
liver
tumors
(gamma
BHC)
93/
69%
/
%
of
liver
tumors
(dieldrin)
100/
87%
(DDT)
77/
87
%
(phenobarbitone)
80/
75%
(beta
BHC)
73/
43
%
Carcinogenicitymouse
(Testing
of
the
substance
Lindane
for
carcinogenic
effects
in
mice
using
oral
administrationduration
80
weeks)
translated
from
German
1975
SPF
mice
ChbbNMRI
100
/
100
50
/50
0
ppm
12.5,
25
or
50
ppm
for
80
wks
incidences
(
/
)
liver
cell
adenomas:
4/
1,
1/
1,
0/
0,
2/
0
lung
tumor:
13/
8,
10/
1,
5/
3,
6/
4
lymphosarcoma
:
5/
12,
0/
7,
1/
3,
2/
5,
respectively
Carcinogenicitymouse
(Pathologic
and
ultrastructural
studies
in
the
hepatocarcinogenic
ity
of
benzene
hexachlooride
in
mice)
published
(1973)
19
groups
(20
40/
group)
,
,
or
BHC
at
100,
250,
or
500
ppm
and
combos
of
250
ppm
ea.
of
with
,
,
or
BHC.
Only
mice
that
were
dosed
w/
BHC
in
combo.
or
alone
developed
nodular
hyperplasia
and
hepatocellular
carcinoma
Carcinogenicitymouse
(Contributions
to
ecological
chemistry
II.
Hepatoma
development
in
mice
after
administration
of
HCH
isomers
in
high
dosage.
Published:
(1972).
8
groups
of
20
ICR
JCL
mice
600
ppm
of
technical
HCH
(I),
HCH
(II)
,
HCH
(III),
HCH
(IV),
a
mix
of
/
HCH
(V),
or
300
ppm
of
HCH
(IX)
5/
10
in
gp
IX
developed
liver
tumors
and
incr.
Liver
wgt.
all
of
group
I
and
II
developed
hepatomas
8/
10
in
gp
V
developed
liver
tumors
and
incr.
Liver
wgt.
28
Carcinogenicitymouse
(Carcinogenicity
of
Benzene
Hexachloride
(BHC))
published:
(1972)
4
groups
of
dd
mice
0,
6.6,
66,
660
ppm
of
technical
BHC
(67%),
(11%),
(15%)
or
(6%)
BHC
and
other
isomers
<
1%
for
24
wks
at
all
doses:
liver
wgt,
cellular
hyperplasia,
nodular
hyperplasia,
all
660
ppm
mice
developed
hepatoma
Carcinogenicitymouse
(Induction
of
hepatoma
in
mice
with
benzene
hydrochloride)
published:
(1973).
4
groups
of
dd
mice
0,
100,
300
or
600
ppm
with
crude
BHC,
or
pure
,
,
or
isomer
for
36
38
wks
No
control
and
100
or
300
ppm
isomer
mice
developed
hepatomas
many
mice
in
crude
BHC,
or
pure
isomer
developed
hepatoma,
Chronic
feeding
Dogs
(Lindane
toxicity
study
in
beagle
dogs)
1970
4
group
of
4
beagles/
sex
0,
25,
50,
or
100
ppm
for
104
wks
NOAEL:
50
ppm
LOAEL:
100
ppm
liver
changes,
slight
inc
liver
wt.
| epa | 2024-06-07T20:31:43.129202 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0202-0011/content.txt"
} |
EPA-HQ-OPP-2002-0202-0012 | Supporting & Related Material | "2002-08-14T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
July
31,
2002
MEMORANDUM
SUBJECT:
Revised
EFED
RED
Chapter
for
Lindane
PC
Code
No.
009001;
Case
No.
818566;
DP
Barcodes:
D254764
TO:
B.
Shackleford,
Branch
Chief
M.
Howard,
Team
Leader
Special
Review
and
Reregistration
Division
(7508C)
FROM:
ERB
V
RED
Team
for
Lindane:
N.
E.
Federoff,
Wildlife
Biologist,
Ecological
Effects
Reviewer,
Team
Leader
F.
A
Khan,
Ph.
D.,
Environmental
Scientist,
Long
range
Transport
Assessor
J.
Melendez,
Chemist,
Environmental
Fate
Reviewer
Environmental
Fate
and
Effects
Division
(7507C)
THROUGH:
Mah
T.
Shamim,
Ph.
D.,
Chief
Environmental
Risk
Branch
V
EFED
(7507C)
The
EFED
Integrated
Environmental
Risk
Assessment
for
Lindane
is
attached.
The
following
is
an
overview
of
our
findings:
Major
Conclusions
Lindane
is
a
persistent
and
moderately
mobile
organochlorine
compound.
Lindane
is
a
potential
endocrine
disruptor
in
birds,
mammals
and
possibly
fish.
There
is
a
possibility
of
acute
and
chronic
risk
to
avian
and
mammalian
species
consuming
a
majority
of
their
body
weight
in
treated
seed
per
day.
Based
on
a
Tier
I
screening
assessment
(using
GENEEC),
the
aquatic
assessment
resulted
in
risks
to
aquatic
organisms.
For
estuarine/
marine
invertebrates,
possible
high
acute
risk
may
occur
even
at
the
low
application
rates
for
seed
treatment
uses.
Restricted
use
LOC's
were
exceeded
for
estuarine/
marine
invertebrates
and
freshwater
fish.
Endangered
species
LOC's
are
exceeded
for
freshwater
fish
and
invertebrates.
Chronic
risk
to
estuarine/
marine
organisms
could
not
be
assessed
due
to
a
lack
of
data.
Modeling
studies
showed
that
lindane
concentrations
in
both
surface
and
ground
water
may
reach
environmentally
significant
levels
(>
MCL),
even
when
lindane
is
restricted
to
seed
treatment
uses
only.
However,
the
modeling
assumption
that
100%
of
the
compound
will
disassociate
from
the
seed
surface
may
have
produced
highly
conservative
estimates
and
has
thus
overestimated
the
EEC's
and
resulting
risks.
Nevertheless,
due
to
the
compound's
persistence,
residues
continue
to
last
in
various
environmental
media
and
probably
is
associated
with
longrange
transport.
Risk
Factors
Produces
significant
reproductive
effects
in
birds
(including
eggshell
thinning)
and
small
mammals.
Lindane
is
a
lipophilic
compound
and
has
been
found
in
milk
from
exposed
lactating
females.
Based
on
available
literature,
lindane
has
shown
endocrine
disrupting
effects
in
birds,
mammals
and
possibly
in
fish.
Very
persistent
and
moderately
mobile.
In
aerobic
soil
systems,
lindane
degrades
very
slowly.
The
registrant
calculated
half
life
was
980
days
(MRID
406225
01).
Very
highly
toxic
to
a
broad
spectrum
of
aquatic
species.
Possible
Mitigating
Factors
Seeds
that
are
incorporated
in
soil
may
reduce
exposure
rates
to
terrestrial
wildlife.
Low
use
rates.
It
appears
that
at
least
two
bird
species
(quail
and
red
winged
blackbird)
were
averse
to
consuming
lindane
treated
seeds
in
laboratory
studies,
which
may
decrease
exposure,
thus
reducing
risk.
Lindane
is
bio
concentrated
rapidly
in
microrganisms,
invertebrates,
fish,
birds
and
mammals,
however
bio
transformation
and
elimination
are
relatively
rapid
when
exposure
is
discontinued
The
modeling
assumption
that
100%
of
the
compound
will
disassociate
from
the
seed
surface
has
likely
produced
highly
conservative
estimates
and
has
thus
overestimated
the
EEC's
and
resulting
risks.
EFED
believes
that
a
seed
leaching
study
would
greatly
increase
certainty
regarding
a
more
realistic
estimate
of
the
amount
of
available
lindane
on
the
seed
surface
and
leaching
from
the
seed
surface.
This
in
turn
would
allow
a
refinement
of
exposure
estimates
and
environmental
concentration
values
(EECs).
Risks
to
Terrestrial
Organisms
Seed
treatment
uses
present
acute
and
chronic
risk
to
birds
and
mammals.
Also,
due
to
lindane's
potential
endocrine
disrupting
character,
mammals
and
birds
that
ingest
seeds
may
be
at
some
additional
risk.
Also,
in
addition,
there
is
a
possibility
of
acute
risk
to
small
mammals
with
high
metabolic
rates
that
dig
and
cache
seeds.
Chronic
risk
to
these
species
may
be
greater
during
breeding
season
due
to
high
seed
consumption
over
time
and
the
persistence
of
the
compound
in
soil.
There
is
a
reduced
acute
risk
to
waterfowl
and
upland
gamebirds
from
seed
treatment.
However,
there
is
acute
risk
to
songbirds
(passerines)
and
other
similar
seed
eating
avian
species.
Lindane
is
highly
toxic
(0.
2
to
0.
56
µ
g/
bee)
to
honeybees.
However,
since
this
is
a
seed
treatment
application,
low
risk
is
assumed
to
flying
insects,
although
beneficial
soil
dwelling
insects
may
be
at
some
risk.
Risks
to
Aquatic
Organisms
Restricted
use
and
endangered
species
LOC's
are
exceeded
(RQ=
0.40)
for
freshwater
fish.
No
chronic
LOC's
are
exceeded
for
freshwater
fish.
The
acute
endangered
species
LOC
is
slightly
exceeded
(RQ=
0.07)
for
freshwater
invertebrates.
No
chronic
LOC's
are
exceeded
for
freshwater
invertebrates.
No
acute
LOCs
were
exceeded
for
estuarine/
marine
fish.
Chronic
risk
to
estuarine/
marine
fish
could
not
be
assessed
due
to
a
lack
of
toxicity
data.
Acute,
restricted
use
and
endangered
species
LOC's
were
exceeded
(RQ=
8.7)
for
estuarine/
marine
invertebrates.
However,
there
are
no
estuarine/
marine
invertebrates
listed
as
endangered.
Chronic
risk
to
estuarine/
marine
invertebrates
could
not
be
assessed
due
to
a
lack
of
toxicity
data.
Risks
to
Endangered
Species
Endangered
birds
and
especially
small
mammals
that
eat
a
large
daily
proportion
of
seeds
may
be
at
risk
from
the
proposed
seed
treatment
use
pattern.
Endangered
freshwater
fish
and
invertebrates
may
also
be
at
acute
risk.
Also,
exposed
endangered
birds,
mammals
and
possibly
fish
may
be
at
risk
due
to
the
potential
endocrine
disrupting
properties
of
lindane
combined
with
already
limited
population
sizes
and/
or
losses
in
critical
habitat.
Incident
reports
Incident
reports
submitted
to
EPA
involving
lindane
have
been
tracked
by
Incident
Data
System
(IDS),
microfiched,
and
then
entered
into
a
second
database,
the
Ecological
Incident
Information
System
(EIIS).
Since
1971,
only
four
incidents
which
involve
fish
kills
have
been
reported
that
are
related
to
lindane
use.
The
most
recent
incident
occurred
in
1995
in
which
hundreds
of
trout
were
killed
on
a
tree
farm
in
North
Carolina
after
a
spill
close
to
a
nearby
stream.
In
1993,
an
incident
was
reported
that
involved
approximately
60
trout
in
California,
and
the
other
two
incidents
were
reported
1971
and
1983.
However,
no
aquatic
incidents
have
been
reported
as
having
occurred
under
the
normal
use
conditions
of
seed
treatment
under
soil
incorporated
use
patterns.
Water
Resource
Assessment
Fate
studies
show
that
lindane
is
both
moderately
mobile
(mean
Koc
=
1368)
and
highly
persistent
(soil
half
life
of
2.
6
years).
Even
considering
lindane's
very
low
use
rate
under
the
current
use
restriction
to
seed
treatment
(maximum
of
0.
0512
lb
a.
i./
acre),
lindane
concentrations
may
be
expected
to
reach
water
resources
at
environmentally
significant
levels.
Modeling
studies
showed
that
lindane
concentrations
in
both
surface
and
ground
water
may
reach
environmentally
significant
levels
(>
MCL),
even
when
lindane
is
restricted
to
seed
treatment
uses
only.
This
conclusion
is
based
solely
on
lindane's
use
as
a
seed
treatment
and
does
not
consider
past
uses
of
lindane.
However,
note
that
lindane
continues
to
persist
in
the
environment
from
past
uses.
Endocrine
Disruption
Based
on
available
scientific
literature,
lindane
has
the
potential
to
be
an
endocrine
disrupting
compound
in
birds,
mammals,
and
possibly
in
fish.
Thus
the
following
language
is
recommended:
EPA's
Interim
Policy
for
Potential
Endocrine
Disruptors
EPA
is
required
under
the
Federal
Food,
Drug
and
Cosmetic
Act
(FFDCA),
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(including
all
pesticide
active
and
other
ingredients)
"may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturallyoccurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
the
recommendations
of
its
Endocrine
Disruptor
Screening
and
Testing
Advisory
Committee
(EDSTAC),
EPA
determined
that
there
was
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticide
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(EDSP).
When
the
appropriate
screening
and
or
testing
protocols
being
considered
under
the
Agency's
Endocrine
Disruptor
Screening
Program
have
been
developed,
lindane
may
be
subjected
to
additional
screening
and
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.
Other
Concerns
Formulations:
Many
formulated
products
containing
lindane
also
contain
other
active
ingredients
(Pentachloronitrobenzene,
Captan,
Diazanon,
Metalaxyl,
Thiram,
Carboxin,
Maneb
and
Mancozeb)
which
can
be
as
toxic
or
more
toxic
than
lindane
alone.
It
is
not
known
if
the
combination
of
lindane
and
these
other
actives
ingredients
are
more
toxic
than
either
is
separately
or
if
there
may
be
toxic
synergism.
Thus,
testing
with
certain
formulated
products
may
be
required.
The
registrant
is
requested
to
submit
any
available
information
on
the
toxic
synergism
of
these
chemicals.
Data
Gaps
Environmental
Fate:
The
environmental
fate
database
for
lindane
is
largely
complete
and
adequate
for
the
present
risk
assessment.
However,
an
anaerobic
soil
metabolism
study
is
required
for
outdoor
seed
treatment
uses
(Memo
from
Denise
Keehner
re:
EFED
policy
guidance
for
eco
risk
and
drinking
water
assessments
of
seed
treatment
pesticides,
7/
30/
99).
EFED
also
believes
that
a
seed
leaching
study
would
greatly
increase
certainty
regarding
a
more
realistic
estimate
of
groundwater
leaching
and
runoff.
This
in
turn
would
allow
a
refinement
of
exposure
estimates
and
environmental
concentration
values
(EECs).
EFED
has
issued
a
guidance
for
this
study
(Memo
from
Denise
Keehner
re:
Standard
Method
for
Determining
the
Leachability
of
Pesticides
from
Treated
Seeds,
7/
6/
2000).
Ecotoxicity:
The
environmental
toxicity
database
for
lindane
is
largely
complete
and
adequate
for
the
present
risk
assessment.
However,
Tier
I
plant
toxicity
studies
(850.4100
Seedling
emergence
in
10
species
and
850.5400
Aquatic
plant
toxicity
tests
in
5
species)
are
required
for
outdoor
seed
treatment
uses
(Memo
from
Denise
Keehner
re:
EFED
policy
guidance
for
eco
risk
and
drinking
water
assessments
of
seed
treatment
pesticides,
7/
30/
99).
In
addition,
the
avian
reproduction
study
(Mallard
duck)
needs
to
be
repeated.
Although
the
submitted
study
(MRID
448671
01)
was
classified
as
being
supplemental
due
to
guideline
deviations
as
well
as
the
low
hatching
success
in
the
control
group,
the
study
should
be
repeated
to
determine
if
15
ppm
is
a
valid
NOAEL
value.
The
NOAEL
value
of
15
ppm
will
be
used
in
risk
assessments
until
further
data
is
provided.
Also,
due
to
the
acute
toxicity
of
lindane
(LC50s
or
EC50s
<
1
mg/
l)
to
estuarine/
marine
fish
and
invertebrates,
and
concentrations
that
may
reach
estuarine/
marine
systems,
chronic
studies
are
required
(72
4
a
and
b:
Estuarine/
Marine
Fish
Early
Life
Stage
and
Estuarine/
Marine
invertebrate
life
cycle).
An
estuarine/
marine
fish
early
life
stage
and
estuarine/
marine
invertebrate
life
cycle
toxicity
test
using
the
TGAI
are
required
for
lindane
because
the
end
use
product
may
be
expected
to
be
transported
to
an
aquatic
environment
from
the
intended
use
site,
aquatic
acute
LC50/
EC50s
were
less
than
1
mg/
l
and
studies
of
other
organisms
indicate
the
reproductive
physiology
of
fish
and/
or
invertebrates
may
be
affected.
Also,
the
persistence
of
lindane
is
>
900
days.
The
preferred
test
species
are
sheepshead
minnow
and
mysid
shrimp.
Aquatic
testing
will
be
held
in
reserve
until
a
seed
leaching
study
is
submitted.
Lastly,
there
is
evidence
that
seed
eating
birds
may
not
be
exposed
due
to
aversion
to
the
compound.
However,
The
Agency
does
NOT
have
any
such
data
for
seed
eating
mammals.
Thus,
it
may
be
beneficial
for
submission
of
such
data
to
better
characterize
risk
to
seed
eating
mammals.
Labeling
Recommendations
EFED
recommends
that
the
labels
for
all
lindane
products
carry
the
following
statements:
Environmental
Hazards
Manufacturing
Use:
This
pesticide
is
toxic
to
fish,
birds,
and
other
wildlife.
Do
not
discharge
effluent
containing
this
product
into
lakes,
streams,
ponds,
estuaries,
oceans,
or
other
waters
unless
in
accordance
with
the
requirements
of
a
National
Pollutant
Discharge
Elimination
System
(NPDES)
permit
and
the
permitting
authority
has
been
notified
in
writing
prior
to
discharge.
Do
not
discharge
effluent
containing
this
product
into
sewer
systems
without
previously
notifying
the
sewage
treatment
plant
authority.
For
guidance
contact
your
State
Water
Board
or
Regional
Office
of
the
USEPA.
End
Use
Products:
Granular/
Seed
Treatment
This
product
is
toxic
to
fish,
birds,
and
other
wildlife.
Exposed
treated
seeds
may
be
hazardous
to
birds
and
other
wildlife.
Dispose
of
all
excess
treated
seeds
by
burial
away
from
bodies
of
water.
Do
not
apply
directly
to
water.
Do
not
contaminate
water
by
disposing
of
equipment
washwaters.
Apply
this
product
only
as
specified
on
the
label.
1
LINDANE
RED
Chapter:
Environmental
Fate
and
Ecological
Risk
Assessment:
Seed
treatment
Prepared
by:
N.
E.
Federoff,
Wildlife
Biologist,
Team
Leader
F.
A.
Khan
Environmental
Scientist
J.
L.
Melendez,
Chemist
United
States
Environmental
Protection
Agency
Office
of
Pesticide
Programs
Environmental
Fate
and
Effects
Division
Environmental
Risk
Branch
V
401
M
Street,
SW
Mail
Code
7507C
Washington,
DC
20460
Reviewed
and
approved
by:
M.
Shamim,
Chief,
ERB
5
2
EXECUTIVE
SUMMARY
Lindane
is
a
persistent
and
moderately
mobile
organochlorine
compound.
At
present,
there
is
only
one
agricultural
use
(seed
treatment)
that
might
affect
the
environment.
Lindane
is
a
potential
endocrine
disruptr
in
birds,
mammals
and
possibly
fish.
There
is
a
possibility
of
acute
and
chronic
risk
to
granivorous
avian
and
mammalian
species.
However,
at
least
two
bird
species
(quail
and
red
winged
blackbird)
were
averse
to
consuming
lindane
treated
seeds
in
a
laboratory
environment,
which
may
drastically
decrease
exposure,
thus
reducing
risk.
In
the
field
,
Blus
et
al.
(1985)
found
that
when
lindane
was
substituted
for
heptaclor
(HE)
for
treatment
of
seed
(Columbia
Basin
near
the
Umatilla
NWR,
in
Oregon
and
Washington
State,
USA),
lindane
did
not
produce
adverse
effects
in
birds
and
residues
were
not
detected
in
either
their
eggs
or
brains.
Also,
coincidental
with
the
decrease
in
HE
residues
in
Canada
geese,
mortality
decreased,
reproductive
success
improved,
and
the
population
increased
rapidly
(Blus
et
al.
1984).
There
was
no
evidence
for
either
bio
magnification
of
lindane
residues
from
treated
seeds
to
goose
tissues
or
eggs,
or
for
induction
of
adverse
effects
to
avian
species.
This
may
be
due
to
the
fact
that
Canada
geese,
as
well
as
other
avian
species,
may
have
been
repelled
by
lindane
treated
seed
as
a
submitted
study
has
suggested
with
quail
and
red
winged
blackbirds.
A
Tier
I
screening
assessment
(using
GENEEC)
indicated
risks
to
aquatic
organisms.
For
estuarine/
marine
invertebrates,
high
acute
risk
may
occur
even
at
the
low
application
rates
for
seed
treatment
uses.
Restricted
use
LOC's
were
exceeded
for
estuarine/
marine
invertebrates
and
freshwater
fish.
Endangered
species
LOC's
are
exceeded
for
freshwater
fish
and
invertebrates
and
estuarine/
marine
invertebrates.
However,
there
are
no
estuarine/
marine
invertebrates
listed
as
endangered.
Chronic
risk
to
estuarine/
marine
organisms
could
not
be
assessed
due
to
a
lack
of
data.
Screening
level
Tier
I
modeling
studies
showed
that
lindane
concentrations
in
both
surface
and
ground
water
may
reach
environmentally
significant
levels
(>
MCL),
even
when
lindane
is
restricted
to
seed
treatment
uses
only.
The
modeling
assumption
that
100%
of
the
compound
will
disassociate
from
the
seed
surface
may
have
produced
highly
conservative
estimates
and
may
have
overestimated
the
EEC's
and
resulting
risks.
A
seed
leaching
study
would
greatly
increase
certainty
regarding
a
more
realistic
estimate
groundwater
leaching
and
runoff.
This
in
turn
would
allow
a
refinement
of
exposure
estimates
and
environmental
concentration
values.
Mode
of
Action
Technical
HCH
consists
of
a
number
of
isomers:
alpha
(
),
beta
(
),
and
gamma
(
)
(known
as
lindane).
The
approximate
composition
of
technical
HCH
is
55
70%
HCH,
5
14%,
HCH,
10
18%,
HCH
and
impurities.
Lindane
(99.5%
HCH)
is
the
most
biologically
active
insecticidal
isomer.
In
insects,
lindane
acts
through
the
inhibition
of
the
gamma
aminobutyric
acid
(GABA)
receptor
of
the
CNS.
GABA
operates
by
increasing
chloride
ion
permeability
into
neurons
thereby
inhibiting
neurostimulation
inducing
overstimulation
of
the
CNS
causing
rapid
violent
convulsions.
The
a
isomer
is
much
less
active
at
inhibiting
binding
to
the
GABA
receptor
than
lindane
and
the
beta
isomer
seems
not
to
exhibit
inhibiting
binding
at
all.
3
Cl
Cl
Cl
Cl
Cl
Cl
Alpha
HCH
Cl
Cl
Cl
Cl
Cl
Cl
Delta
HCH
Cl
Cl
Cl
Cl
Cl
Cl
Beta
HCH
Cl
Cl
Cl
Cl
Cl
Cl
Lindane
(gamma
HCH)
Figure
1:
Chemical
Structure
of
Lindane
and
Isomers
Use
Characterization
Although
the
only
current
agricultural
use
of
lindane
is
for
seed
treatment,
lindane
has
been
extensively
used
in
the
past
as
an
insecticide
on
a
variety
of
crops,
for
home
termite
control,
and
as
a
wood
preservative.
Table
1
summarizes
the
current
use
rates
for
seed
treatment
that
were
used
in
this
risk
assessment.
Table
1.
Lindane
seed
treatment
uses
and
application
rates.
Seed
Type
Label
Rate
[lb
a.
i./
100
lb
seed]
Typical
Seeding
a
[lbs
seed/
acre]
Estimated
Application
Rate,
based
on
label
rate
and
maximum
seeding
[lb.
a.
i./
acre]
Barley
0.0375
60
96
0.036
Corn
0.125
10
14
0.018
Oats
0.03125
50
80
0.025
Rye
0.
0328
56
84
0.0276
Sorghum
0.0628
6.76
0.00425
Canola
1.075
1.456
4
0.
043
0.059
Wheat
0.0426
40
120
0.0512
a
Based
on
information
from
BEAD.
ENVIRONMENTAL
FATE
AND
TRANSPORT
ASSESSMENT
Summary
Laboratory
studies
indicate
that
lindane
is
persistent
and
moderately
mobile.
It
is
resistant
to
photolysis
and
hydrolysis
(except
at
high
pH),
and
degrades
very
slowly
by
microbial
actions.
Table
2
summarizes
the
physical
chemical
and
environmental
fate
properties
of
lindane.
Since
most
degradation
pathways
occur
slowly,
the
presence
of
the
degradates
is
generally
at
relatively
low
levels.
There
is
possible
evidence
that
lindane
transforms
to
the
alpha
isomer
of
hexachlorocyclohexane
by
biological
degradation
although
this
issue
remains
to
be
conclusively
resolved.
Possible
degradates
could
include
isomers
of
pentachlorocyclohexene,
1,2,4,
trichlorobenzene,
and
1,
2,
3
trichlorobenzene.
Lindane
is
transported
through
the
environment
by
both
hydrologic
and
atmospheric
means.
Lindane
has
often
been
detected
in
surface
and
ground
water,
and
in
areas
of
non
use
(e.
g.,
the
arctic),
indicating
global
4
atmospheric
transport
(see
long
range
transport
section).
Most
of
these
detections
have
likely
resulted
from
a
combination
of
lindane's
past
widespread
use
and
its
extreme
persistence.
Currently,
U.
S.
agricultural
uses
of
lindane
are
restricted
to
seed
treatments,
and
application
rates
are
quite
low.
Based
on
a
screening
level
assessment,
lindane
may
reach
water
resources
at
levels
above
the
MCL
of
0.
2
µg/
L.
Table
2.
Physical
chemical
properties
of
lindane.
Parameters
Value
Chemical
name
1,
2,
3,
4,
5,
6
hexachlorocyclohexane
CAS
No..
58
89
9
Molecular
Weight
290.82
Solubility
7
mg/
l
Vapor
Pressure
9.4
x
10
6
torr
Henry's
Law
Constant
@
2
5
C
10
2.49
pH
5
Hydrolysis
half
life
stable
pH
7
Hydrolysis
half
life
stable
pH
9
Hydrolysis
half
life
43
53
days
Soil
Photolysis
half
life
stable
Aquatic
photolysis
half
life
stable
Aerobic
soil
dissipation
half
life
980
days
Soil
organic
carbon
partitioning
(Koc
)
1368
mL/
g
(mean
of
4
soils)
Octanol
water
partition
coefficient
(Kow
)10
3.78
Hydrolysis
Lindane
is
stable
to
hydrolysis
at
pH
5
and
7
and
has
a
half
life
of
from
43
53
days
at
pH
of
9
(MRID
00161630).
At
pH
9,
the
degradates
were
pentachlorocyclohexane,
1,2,4,
trichlorobenzene,
and
1,
2,
3trichlorobenzene
Quantitative
data
were
not
provided
for
the
degradates
in
the
submitted
document.
Aqueous
Photolysis
Lindane
is
stable
to
photolysis
in
aqueous
systems.
These
studies
(MRIDs
0016457;
001645545;
447931)
showed
no
evidence
of
aqueous
photodegradation
during
the
30
day
study
period,
even
when
acetone
was
used
as
a
photosensitizer
(MRID
001645545).
Soil
Photolysis
Lindane
in
contact
with
soil
does
not
photodegrade
significantly.
On
a
1
mm
thick
soil
specimen
exposed
to
artificial
sunlight
for
12
hour
per
day,
lindane
degraded
only
very
slightly
over
the
30
day
test
period.
The
extrapolated
half
life
was
greater
than
150
days
(MRID
444406
05).
The
dark
control
showed
a
5%
loss
over
the
30
day
study.
The
soil
degradation
half
life
with
consideration
for
the
dark
control
losses
is
200
days.
Because
of
the
extreme
extrapolation
to
obtain
a
half
life,
this
study
essentially
gives
no
evidence
of
lindane
photodegradation
on
soil.
Aerobic
Soil
Metabolism
In
a
336
day
aerobic
soil
metabolism
study,
lindane
degraded
very
slowly,
with
a
registrant
calculated
half
life
of
980
days
(MRID
406225
01).
Minor
degradation
products
were
PCCH
and
BHC,
which
reached
maximums
of
3.
84%
and
0.
77%
of
applied
radioactivity,
respectively.
Total
CO2
production
was
4.
81%
of
the
applied
parent
radioactivity
at
day
336.
It
was
confirmed
that
both
compounds
were
present
at
the
beginning
of
the
study;
however,
it
was
also
observed
that,
even
though
there
was
some
variability
in
the
data,
pentachlorocyclohexene
(PCCH)
showed
a
continuous
increment
in
concentration
from
day
0
to
day
336
(last
test
interval)
of
the
study.
In
general,
it
appeared
that
there
was
metabolic
transformation
during
5
the
study,
where
pentachlorocyclohexene
was
formed
slowly.
Although
microbial
transformation
of
lindane
to
HCH
is
technically
possible,
it
does
not
occur
to
a
significant
extent.
Lindane
can
isomerize
to
HCH
by
both
photolysis
and
microbial
degradation,
although
significant
conversion
under
typical
environmental
conditions
has
not
been
demonstrated
for
either
pathway.
Anaerobic
Soil
Metabolism
This
study
is
at
best
considered
only
marginally
useful,
mainly
because
the
material
balances
generally
decreased
throughout
the
study
period
and
were
unacceptably
low,
and
because
there
was
variability
of
in
the
data
for
the
parent
compound.
Lindane
degraded
with
a
DT50
of
36.5
days
in
anaerobic
(nitrogen)
flooded
sandy
loam
soil
that
was
incubated
in
darkness
up
to
60
days
following
a
31
day
aerobic
incubation
period.
During
the
aerobic
phase,
the
parent
compound
was
sampled
only
at
the
initial,
14
days,
and
31
days
(prior
to
flooding).
During
that
time,
the
parent
decreased
from
97.6%
of
the
applied
radioactivity
to
69.6%
at
31
days
post
treatment.
The
registrant
proposed
to
estimate
the
half
life
of
the
aerobic
soil
metabolism
of
lindane
based
on
the
extrapolation
of
the
31
day
aerobic
portion
of
the
study.
However,
close
inspection
of
the
data
indicates
poor
recovery
of
the
radioactivity
(from
103.0%
at
the
initial
to
85.74%
at
31
days.
Furthermore,
only
three
data
points
are
available
for
the
calculation.
EFED
believes
that
to
estimate
a
half
life
of
aerobic
soil
metabolism
under
these
conditions
is
inappropriate.
After
anaerobic
conditions
were
induced
by
flooding
and
nitrogen
gas,
the
parent
compound
in
the
total
soil/
water
system
was
initially
69.
6%
(at
day
0
prior
to
flooding),
but
it
increased
to
77.1%
of
the
applied
radioactivity
by
3
days.
Total
volatiles
(including
CO2
)
were
39.2%
at
60
days;
14
CO2
(NaOH
trap
only)
was
a
maximum
of
6.
0%
by
60
days.
At
60
days
following
initiation
of
anaerobic
conditions,
12.
5%
of
the
applied
radioactivity
was
present
as
volatile
parent
compound.
In
the
volatile
phase,
a
major
degradate
to
11.
8%
by
60
days
following
the
initiation
of
anaerobic
conditions.
The
registrant
attempted
to
identify
the
degradate.
It
eluted
on
GC
trials
at
10.1
minutes.
When
the
sample
was
spiked
with
HCH,
it
eluted
with
the
unknown,
suggesting
the
presence
of
HCH.
However,
this
could
not
be
confirmed
by
a
second
analytical
technique,
namely,
HPLC.
In
addition,
the
registrant
provided
another
study,
MRID#
44867107,
which
is
a
non
guideline
study.
Mobility
The
registrant
calculated
organic
carbon
partitioning
coefficient
(Koc
)
ranged
from
942
to
1798
mL/
g
with
a
mean
of
1368
mL/
g
for
the
four
soils
tested
(MRID
00164346).
EFED
considers
compounds
with
this
range
of
Koc
values
to
be
moderately
mobile.
Sorption
of
lindane
was
assessed
in
24
hour
batch
sorption
studies.
Soil
characteristics
and
results
are
presented
in
Table
3.
Table
3.
Soil
descriptions
and
results
of
24
hour
batch
adsorption
studies
of
lindane.
Texture
Clay
Loam
Loam
Loamy
Sand
Sand
Sand
46
46
82
88
Silt
25
29
8
7
Clay
29
25
10
5
Organic
Carbon
(%)
0.99
1.58
1.58
0.39
CEC
[meq/
100
g]
19.4
22.2
18.2
8.
9
pH
7.84
7.22
6.9
7.
75
Kf
[(
ml/
g)(
mg/
L)
1
n
]
a
16.8
14.9
28.4
3.
83
N
a
0.96
0.92
0.93
0.89
Koc
[mL/
g]
b
1696
942
1798
1037
a
Defined
by
the
Freundlich
isotherm:
S=
KF
C
N
where
S
is
sorbed
concentration
[mg/
kg],
and
C
is
aqueous
concentration
[mg/
L].
b
Koc
is
taken
as
the
organic
carbon
partitioning
coefficient
at
an
aqueous
concentration
of
1
mg/
L.
6
Laboratory
Volatility
The
submitted
study
provides
only
supplemental
information
about
the
volatility
of
lindane.
The
study
was
initially
designed
and
submitted
to
European
agencies.
The
registrant
submitted
supplemental
calculations
along
with
the
original
submission.
Lindane
volatilized
moderately
after
application.
Immediately
after
application,
a
1.
5
cm
layer
of
soil
was
placed
on
top
of
the
treated
soil
(according
to
the
registrant
this
would
simulate
soil
incorporation
similar
to
the
actual
use
as
a
seed
protectant).
During
the
first
hour
2.
19%
of
the
applied
lindane
was
found
in
the
volatile
traps.
The
calculated
mean
volatilization
rate
of
lindane
was
0.
290
µg/
cm
2
/hr.
The
rate
of
volatilization
decreased
with
time
to
an
average
of
0.
0347
µg/
cm
2
/hr
in
the
6
24
hour
interval.
After
24
hours,
about
13%
of
the
applied
radioactivity
was
volatilized.
Lindane
represented
>86%
of
the
radioactivity
extracted
from
the
traps
(MRID#
44445301).
Terrestrial
Dissipation
Lindane,
at
0.61
lbs
a.
i./
A,
was
applied
at
once
to
two
test
plots
(loamy
sand,
pH
5.2)
cropped
with
peaches
and
bareground,
located
in
Georgia.
Lindane
dissipated
slowly,
with
calculated
half
lives
of
65
and
107
days
for
cropped
and
bareground
soils,
respectively,
based
on
the
average
of
3
values
of
lindane
in
the
0
5
cm
soil
depth.
Lindane
was
reported
to
be
in
the
5
10
cm
soil
depth
between
days
120
and
185,
at
levels
between
0.04
0.05
ppm.
(MRID
40622502)
In
another
terrestrial
field
dissipation
study
(MRID
448671
03),
lindane
was
applied
uniformly
to
a
field
in
California
at
a
target
rate
that
was
8
times
higher
than
the
label
application
rate
for
seed
treatment.
Results
from
day
0
measurements
indicated
that
58%
of
the
target
rate
was
actually
applied.
Lindane
residues
were
not
detected
below
6
inches.
However,
the
quantification
limit
was
0.
02
ppm,
which
is
only
about
5%
of
the
original
concentration;
thus
lindane
in
this
study
that
leached
below
the
6
inches
could
have
easily
remain
unquantified,
and
thus
dissipation
half
lives
may
be
underestimated.
The
registrant
calculated
dissipation
half
life
was
25
days.
Dissipation
half
lives
are
typically
shorter
in
the
field
than
data
from
laboratory
studies
due
to
volatilization,
run
off
and
other
such
variables.
Degradates
were
not
monitored.
Bioconcentration
Lindane
bioconcentrates
appreciably,
but
depurates
rapidly.
Bioconcentration
studies
were
conducted
with
bluegill
sunfish
(Lepomis
macrochirus)
at
nominal
concentration
of
0.
54
µg/
L
of
lindane
for
28
days,
followed
by
14
days
of
depuration
(MRID
400561
01).
Bioconcentration
factors
were
780
for
fillet,
2500
for
viscera,
and
1400
for
whole
fish
tissues.
After
the
14
days
of
depuration,
14
C
levels
were
reduced
by
96%
in
fillet,
95%
in
viscera,
and
85%
in
whole
fish.
Once
released
into
the
environment,
lindane
can
partition
into
all
environmental
media.
Lindane
has
been
detected
in
air,
surface
water,
groundwater,
sediment,
soil,
ice,
snowpack,
fish,
wildlife
and
humans.
Lindane
can
bio
accumulate
easily
in
the
food
chain
due
to
its
high
lipid
solubility
and
can
bio
concentrate
rapidly
in
microrganisms,
invertebrates,
fish,
birds
and
mammals,
however
bio
transformation
and
elimination
are
relatively
rapid
when
exposure
is
discontinued
(WHO
1991).
Water
Resource
Assessment
Lindane
may
reach
surface
and
ground
waters
when
used
as
a
seed
treatment,
although
concentrations
are
expected
to
be
low.
Fate
studies
show
that
lindane
is
both
moderately
mobile
(mean
Koc
=
1368)
and
persistent
(soil
half
life
of
2.
6
years).
Based
on
a
screening
level
assessment,
even
at
its
very
low
use
rate
under
the
current
use
restriction
to
seed
treatment
(maximum
of
0.
0512
lb
a.
i./
acre),
lindane
may
reach
water
resources
at
environmentally
significant
concentrations.
7
Surface
Water
(Farm
Pond)
Surface
water
concentrations
resulting
from
lindane
use
as
a
seed
treatment
were
predicted
with
the
Tier1
assessment
model,
GENEEC.
Table
4
presents
a
summary
of
GENEEC
inputs
and
results.
The
entire
output
file
can
be
found
in
Appendix
III.
Table
4.
GENEEC
input
parameters
and
results
for
lindane.
Application
Rate
1
x
0.
051
lb
ai/
acre*
Aerobic
Soil
Half
Life
980
days
(single
value)
Organic
Carbon
Partitioning
Coefficient
(Koc
)
942
mL/
g
(lowest
value)
Peak
0.67
µg/
L
4
day
average
0.66
µg/
L
21
day
average
0.58
µg/
L
56
day
average
0.48
µg/
L
*The
highest
effective
application
rate
was
for
wheat
at
0.0512
lb
a.
i.
/acre
(see
Table
1).
Ground
Water
Ground
water
concentrations
were
predicted
with
SCIGROW.
Input
parameters
and
output
and
the
resulting
EEC
are
summarized
in
Table
5.
The
entire
SCIGROW
output
file
is
located
in
Appendix
III.
Table
5.
SCIGROW
input
parameters
and
results
for
lindane.
Application
Rate
1
@
0.
051
lb/
acre
Aerobic
Soil
Half
Life
980
days
(mean
Value)
Organic
Carbon
Partitioning
Coefficient
(Koc
)
1367
mL/
g
(median
Value)
EEC
0.011
µg/
L
Drinking
Water
Recommendations
to
HED
EFED
recommends
that
the
Health
Effects
Division
(HED)
use
the
concentrations
presented
in
Table
6
for
drinking
water
EECs.
The
drinking
water
EECs
were
based
on
the
GENEEC
(surface
water)
and
SCIGROW
(groundwater)
simulations
described
above.
Table
6.
Drinking
water
EECs
for
lindane
for
use
by
HED.
Acute
Chronic
Groundwater
0.011
µ
g/
L
0.
011
µ
g/
L
Surface
Water
0.67
µ
g/
L
0.
48
µ
g/
L
Monitoring
Data
The
presence
of
lindane
in
the
environment,
due
to
previous
widespread
agricultural
use,
is
well
documented
in
U.
S.
data
bases.
For
example,
In
the
U.
S.
EPA
STORET
data
base,
720
detections
(after
culling
of
data
to
eliminate
dubious
data,
e.
g.
K
and
U
codes)
in
ground
water
were
reported
between
the
years
1968
and
1995,
in
nearly
all
regions
of
the
country,
with
especially
high
numbers
of
detections
in
the
South
and
West.
For
these
720
detections,
the
median
and
mean
concentrations
were
0.01
and
11
µg/
L,
respectively.
For
surface
waters,
8775
detections
were
reported
with
median
and
mean
concentrations
of
0.005
and
0.
18
µg/
L.
STORET
Dectections
were
reported
in
nearly
all
regions
of
the
conterminous
U.
S.
In
the
USGS
NAWQA
study,
lindane
was
detected
in
2.58%
of
surface
water
samples
(0.
67%
at
levels
greater
than
0.05
µ
g/
L,
maximum
concentration
reported
was
0.13
µ
g/
L).
For
groundwater,
USGS
NAWQA
reported
a
detection
frequency
of
0.
1
%
(0.07%
at
levels
greater
than
0.01
µ
g/
L,
maximum
concentration
reported
was
0.032
µ
g/
L).
8
EFED
would
like
to
stress
some
basic
general
parameters
when
considering
the
possible
use
of
these
types
of
monitoring
data
for
lindane:
EFED
believes
that
utilizing
"NAWQA"
and/
or
"STORET"
data
exclusively
to
establish
exposures
or
to
define
aquatic
risk
is
not
appropriate
in
most
cases.
Both
databases
indicate
that
lindane
has
been
found
in
surface
and
ground
water.
There
is
no
indication
that
this
has
changed.
The
models
used
by
EFED
(FIRST
and
GENEEC2)
assume
the
chemical
is
applied
in
the
area
surrounding
the
water
body
from
which
exposures
may
occur.
Random
monitoring
of
agricultural
areas
does
not
automatically
assure
that
lindane
was
used
in
the
basin
surrounding
the
body
of
water
being
sampled.
Also,
neither
NAWQA
nor
STORET
monitoring
programs
are
designed
or
are
intended
to
establish
potential
risk
to
aquatic
organisms
from
agricultural
chemicals.
The
NAWQA
and
STORET
monitoring
programs
are
not
designed,
nor
are
they
intended
to
establish
potential
risk
to
human
health.
NAWQA
and
STORET
are
status
and
trends
program
for
general
water
quality.
Monitoring
is
not
"targeted"
to
specific
pesticides
and
no
validated
link
to
a
pesticides'
use
at
the
field
level
with
an
occurrence
in
either
ground
or
surface
water
has
been
made.
The
Agency
acknowledges
that
lindane's
use
has
decreased
over
time,
and
detections
should
decrease
accordingly,
but,
once
again,
the
purpose
of
the
estimation
of
EEC's
is
to
obtain
potential
concentrations
of
a
pesticide
when
they
are
applied
in
the
proximity
of
surface
water
intakes.
NAWQA
and
STORET
data
are
limited
by
the
extent
of
sampling
conducted
at
any
one
site.
Very
few
sites
were
sampled
more
than
a
few
times
in
a
year
and
still
fewer
for
more
than
one
year.
Information
such
as,
but
not
limited
to,
the
timing
of
lindane
application,
proximity
to
the
sampling
site
and
proximity
of
sampling
site
to
the
nearest
drinking
water
intake
are
necessary
to
better
characterize
the
usefulness
of
the
monitoring
data.
Long
range
Transport
Potential
of
Lindane
Hexachlorocyclohexane
(HCH)
is
an
organochlorine
pesticide
used
throughout
the
world
and
is
commonly
available
in
two
formulations:
technical
grade
HCH,
consists
of
mainly
HCH
(55
70%),
HCH
1018
and
trace
amounts
of
and
HCH
isomers
(5
14%)
and
lindane
(almost
pure
99.
5%
HCH).
The
United
States
and
many
other
developed
nations
discontinued
and
banned
HCH
usage.
Although
the
only
current
agricultural
use
of
lindane
in
United
States
is
for
seed
treatment,
lindane
has
been
extensively
used
in
the
past
as
an
insecticide
on
a
variety
of
crops,
for
home
termite
control,
and
as
a
wood
preservative.
Numerous
studies
of
ambient
air
(Harner
et
al.,
2001
and
Waite
et
al.,
1999),
precipitation
(Barrie
et
al.,
1992
and
Norstrom
and
Muir,
1994),
and
surface
water
(Harner,
1997
and
Norstrom
and
Muir,
1994)
have
reported
HCH
residues,
particularly
and
isomers,
throughout
North
America.
One
concern
is
whether
the
current
use
of
lindane
in
the
United
States
has
the
potential
of
atmospheric
burdens
that
arise
from
secondary
emissions
owing
to
agricultural
practices
like
seed
treatment
and
consequently
their
potential
for
long
range
transport
and
effects
on
the
ecosystem.
There
are
no
specific
studies
that
have
been
conducted
in
the
United
States
to
address
this
issue.
Therefore,
this
section
relied
on
available
literature
to
address
the
relative
influence
of
local
and
regional
sources
of
lindane
and
their
potential
for
long
range
transport.
Lindane
is
a
relatively
volatile,
persistence
and
lipophilic
organochlorine
pesticide
and
it
can
migrate
over
a
long
distance
through
various
environmental
media
such
as
air,
water,
and
sediment.
Once
lindane
is
applied
to
soil,
it
can
either
persist
in
soil
as
a
sorbed
phase
or
be
removed
through
several
physical,
chemical,
and
biological
processes.
However,
volatilization
from
soil
and
surface
waters
is
the
major
9
dissipation
route
for
lindane.
The
Henry's
law
constant
for
lindane
suggests
that
it
will
volatilize
into
the
air,
although
microbial
and
chemical
degradation
and
uptake
by
crops
can
also
occur
(Walker
et
al.,
1999).
Lindane
can
also
enter
the
air
as
adsorbed
phase
onto
suspended
particulate
matter,
but
this
process
does
not
appear
to
be
a
major
contributor
like
volatilization
(Walker
et
al.,
1999
and
Bidlemen,
1998).
Lane
et
al.
(1992)
reported
that
95%
of
the
HCH
isomers
in
ambient
air
were
the
gaseous
phase.
Brubaker
and
Hites
(1998)
measured
the
gas
phase
kinetics
of
the
hydroxyl
radical
with
HCH
and
HCH,
and
reported
that
these
compounds
have
long
atmospheric
half
lives
in
air
and
therefore
can
be
transported
long
distance.
Recently,
soil
and
air
samples
were
collected
for
organochlorine
pesticides
in
northwest
Alabama
to
estimate
soil
to
air
fluxes
and
their
contribution
to
the
atmospheric
concentration
(Harner
et
al.,
2001).
They
attributed
that
the
atmospheric
concentration
of
lindane
in
northwest
Alabama
is
possibly
due
to
atmospheric
advections
or
regional
sources
rather
than
the
studied
soils.
A
field
study
conducted
by
Waite
et
al.
(2001)
in
Saskatchewan,
Canada
demonstrated
volatilization
of
lindane
from
fields
planted
with
lindane
treated
canola
seed.
They
reported
that
significant
quantities
(12
30%)
of
applied
lindane
volatilize
from
treated
canola
seed
to
the
atmosphere
during
the
growing
seasons
and
have
direct
implications
on
regional
atmospheric
concentrations
of
lindane.
They
have
also
estimated
that
a
range
of
66.4
to188.8
tons
of
atmospheric
load
of
HCH
occurred
during
1997
and
1998
following
the
planting
of
canola
in
the
region
of
the
Canadian
prairies.
Poissant
and
Koprivnjak
(1996)
reported
that
90%
of
elevated
HCH
concentration
in
the
atmosphere
at
Villeroy,
Quebec
in
1992
was
from
secondary
emissions
of
applied
lindane
treated
corn,
while
the
rest
was
from
the
volatilization
of
residual
lindane
from
the
previous
year
seed
treatment.
The
production
and
usage
of
HCH
isomers
(especially
HCH)
have
declined
worldwide
(except
India)
significantly
in
recent
years
(Li
et
al.,
1998).
However,
many
studies
suggest
that
secondary
emissions
of
residual
lindane
continue
to
recycle
in
the
global
system
while
they
slowly
migrated
and
redeposited
in
the
northern
Hemisphere.
Harner
et
al.
(1999)
attributed
the
substantial
increase
of
HCH
compared
to
lindane
in
the
Arctic
to
the
differences
in
deposition
and
photochemical
degradation
of
lindane
to
HCH.
However,
many
other
studies
did
not
find
substantial
evidence
of
photoisomerization
of
lindane
to
HCH
(Walker
et
al.,
1999).
They
also
suggested
that
the
conversion
of
lindane
to
HCH
in
soil
and
sediment
might
occur
and
contribute
a
small
fraction
of
HCH
accumulation
in
atmosphere.
Cleeman
et
al.
(1995)
measured
the
deposition
of
HCH
isomers
at
four
sites
during
1990
to
1992
in
Denmark.
Elevated
levels
of
and
HCHs
were
detected
in
the
spring
and
summer
and
were
attributed
to
continuing
use
of
HCH
isomers
and
long
range
transport
from
European
countries
south
and
west
of
Denmark.
Ockenden
et
al.
(1998)
observed
a
very
similar
trend
in
Norway.
Iwata
et
al.
(1993)
compared
surface
water
and
air
concentrations
of
HCH
isomers.
Results
indicate
that
HCHs
were
primarily
released
from
east
Asia
and
India
but
were
accumulating
in
the
northern
oceans.
They
suggested
that
HCH
isomers
were
able
to
atmospherically
transport
to
colder
regions
where
it
was
deposited
and
became
less
volatile
in
colder
sinks.
Atmospheric
concentrations
of
many
organochlorine
compounds
have
also
been
detected
in
the
Arctic,
but
the
highest
concentrations
are
generally
and
HCHs
(Harner,
1997).
Even
though,
high
concentrations
of
HCH
isomers
were
detected
in
surface
waters
of
the
Arctic,
bioaccumulation
in
the
aquatic
food
chains
was
significantly
less
than
the
other
organochlorine
compounds
(Norstrom
and
Muir,
1994).
The
behavior
of
HCH
isomers
in
the
environment
is
complex
because
they
are
multimedia
chemicals,
existing
and
exchanging
among
different
compartments
of
the
environment
such
as
atmosphere,
surface
water,
soil
and
sediment.
Post
application
residual
volatilization
of
lindane
takes
place
over
a
much
longer
period.
Once
airborne,
lindane
may
move
into
the
upper
troposphere
for
more
widespread
regional,
and
possibly
transcontinental
distribution
as
a
result
of
large
scale
vertical
perturbations
that
facilitate
air
mass
movement
out
of
the
near
surface.
Also,
it
may
reversibly
deposit
on
terrestrial
surfaces
close
to
the
source
and
still
be
transported
over
large
distances,
even
global
scales,
through
successive
cycles
of
deposition
and
10
re
emission
as
result
of
ambient
temperature
and
latitude
differences
known
as
"global
distillation
or
fractionation"
(Wania
and
Mackay,
1996).
In
order
to
understand
the
long
range
transport
potential
of
a
compound,
a
necessary
step
needs
to
consider
if
multimedia
environmental
partition
and
degradation
processes
can
substantially
remove
the
substance.
In
response,
a
number
of
multimedia
models
have
emerged.
Detailed
information
of
multimedia
model
evolution
and
their
significance
can
be
found
in
a
recent
article
by
Wania
and
Mackay
(1999).
Recently,
a
workgroup
was
initiated
by
Wania
and
Mackey
(2000)
to
compare
the
persistent
and
longrange
transport
potential
estimated
by
models
developed
and
used
by
various
research
groups.
Even
though
there
are
some
specific
differences
among
the
participants'
models,
all
participants
used
essentially
the
basic
multimedia
Level
III
fugacity
model
developed
by
Mackey
(1991).
The
Level
III
model
is
more
complex
and
realistic
than
Level
I
and
Level
II
fugacity
models.
A
Level
I
model
is
a
closed
system
mass
balance
of
a
defined
quantity
of
chemical
as
it
partitions
at
equilibrium
between
compartments.
A
Level
II
model
is
a
steady
state
open
system
description
of
chemical
fate
at
equilibrium
with
a
constant
chemical
emission
rate.
The
Level
III
model
is
a
steady
state
of
chemical
fate
between
a
number
of
well
mixed
compartments
which
are
not
at
equilibrium.
This
model
also
assumes
a
simple,
evaluative
environment
with
user
defined
volumes
and
densities
for
the
following
homogeneous
environmental
media
(or
compartments):
air,
water,
soil,
suspended
sediment,
sediment,
fish
and
aerosols.
This
model
gives
a
more
realistic
description
of
a
chemical's
fate
including
the
important
degradation
and
advection
losses
and
the
intermedia
transport
processes.
All
participants
of
the
workgroup
evaluated
the
persistent
and
long
range
transport
of
lindane
and
25
other
chemicals
using
a
set
of
physical,
chemical,
and
environmental
fate
data
by
Mackey
et
al.
(1992
1997).
They
calculated
values
termed
"fugacity
capacities"
for
selected
environmental
media
(air,
water,
soil)
in
the
model,
based
on
the
chemical
and
physical
properties
of
the
modeled
substances.
There
are
large
differences
in
the
absolute
persistence
value
estimated
by
the
various
models
ranging
from
546
days
to
1219
days
for
lindane
and
368
days
to
925
days
for
HCH.
Similarly,
the
absolute
atmospheric
transport
distances
calculated
by
the
participants
are
also
large
ranging
from1000
km(
621
miles)
to58396
km
(36287
miles)
for
lindane
and
1014
km
(630
miles)
to
72441
km
(45014
miles)
for
HCH.
Despite
the
large
difference
in
the
absolute
values,
the
correlation
between
the
overall
persistence
and
long
range
transport
values
obtained
by
various
models
were
high,
with
correlation
coefficients
averaging
higher
than
0.
80.
The
differences
between
models
can
be
attributed
to
the
differences
in
the
numbers
and
relative
dimensions
of
the
model
compartments.
In
addition,
environmental
degradation
rates,
which
can
vary
with
temperature,
humidity,
and
other
environmental
properties,
may
have
significant
influence
on
the
variation
among
model
results.
Currently,
the
EPA
is
developing
a
PBT
Profiler
that
estimates
environmental
persistence
(P),
bioconcentration
potential
(B),
and
aquatic
toxicity
(T).
When
a
user
accesses
the
PBT
Profiler
on
the
Internet,
the
program
prompts
the
user
to
enter
the
Chemical
Abstract
Service
(CAS)
number
of
chemicals
under
consideration.
The
PBT
Profiler
is
linked
to
a
database
containing
CAS
numbers
and
associated
chemical
structure
for
more
than
100,000
discrete
chemical
substances.
If
the
CAS
number
is
in
the
database,
the
PBT
Profiler
will
translate
the
CAS
number
into
a
chemical
structure,
predict
the
PBT
characteristics,
and
provide
a
PBT
Profile
in
an
easy
to
understand
format.
The
PBT
profiler
also
uses
the
Level
III
fugacity
model
as
described
earlier
to
determine
the
percentage
of
a
chemical
in
defined
media.
More
information
can
be
obtained
from
EPA's
website
(www.
epa.
gov/
opptintr/
p2framework/
docs/
profile.
htm).
A
beta
test
of
the
PBT
Profiler
has
been
completed
and
the
peer
review
phase
is
in
progress.
The
PBT
profiler
was
used
to
estimate
PBT
characteristics
of
lindane.
The
following
italicized
or
underlined
highlights
in
PBT
outputs
of
lindane
11
indicate
that
the
persistence
and
aquatic
toxicity
criteria
have
been
exceeded
and
characteristics
travel
distance
(CTD)
or
a
half
distance
(analogous
to
half
life)
was
15000
km
(9321miles).
In
summary,
the
presence
of
HCH
and
lindane
in
surface
water,
atmosphere
and
precipitation
from
sites
remote
from
industrial
and
agricultural
activities
implies
long
range
atmospheric
migrations
of
these
compounds.
Concerns
have
been
raised
for
their
potential
effects
on
human
and
ecosystem
health
of
the
northern
hemisphere.
It
is
conceivable
that
the
elevated
levels
of
lindane
and
HCH
in
the
northern
hemisphere,
especially
in
the
Arctic,
resulted
from
long
range
transport.
Persistence
and
long
range
transport
of
lindane
was
also
reflected
in
monitoring
data
and
various
modeling
efforts.
Despite
the
progress
made
in
recent
years
in
estimating
the
persistence
and
long
ranged
transport
using
models
for
chemicals,
a
validated
global
model
has
not
yet
been
published
because
of
uncertainties
involved
in
the
source
inventories,
chemical
fate
data,
degradative
pathways
and
exposure
analyses.
Future
work
should
be
aimed
at
developing
a
comprehensive
screening
tool
that
can
be
used
reliably
in
risk
assessments
for
regulatory
purposes.
12
ECOLOGICAL
EFFECTS
TOXICITY
ASSESSMENT
Toxicity
testing
reported
in
this
section
does
not
represent
all
species
of
bird,
mammal,
or
aquatic
organism.
Only
two
surrogate
species
for
both
freshwater
fish
and
birds
are
used
to
represent
all
freshwater
fish
(2000+)
and
bird
(680+)
species
in
the
United
States.
For
mammals,
acute
studies
are
usually
limited
to
the
Norway
rat
or
the
house
mouse.
Estuarine/
marine
testing
is
usually
limited
to
a
crustacean,
a
mollusk,
and
a
fish.
Also,
neither
reptiles
nor
amphibians
are
tested.
The
assessment
of
risk
or
hazard
makes
the
assumption
that
avian
and
reptilian
toxicity
are
similar,
and
that
fish
and
amphibians
toxicity
are
similar.
Generally,
the
most
toxic
endpoints
for
the
technical
grade
active
ingredient
(TGAI)
are
used
in
the
assessment
to
represent
each
group
of
organism.
Based
on
ecological
effects
data,
the
toxicity
endpoints
+
used
in
the
assessment
of
lindane
can
be
characterized
as
follows:
*
Avian
acute
oral
Moderately
toxic
(LD50=
56
mg/
Kg)
*
Avian
acute
dietary
Highly
toxic
(LC50=
425
ppm)
*
Avian
chronic
(reproduction)
(NOAEC=
15
ppm)
*
Mammalian
acute
oral
Moderately
toxic
(LD50=
88
mg/
Kg)
*
Mammalian
chronic
(reproduction)(
NOAEL=
20
ppm)
*
Honey
bee
acute
Highly
toxic
(LD50=
0.2
ug/
bee)
*
Fish
(freshwater)
acute
Very
highly
toxic
(LC50=
1.7
ppb)
*
Fish
(freshwater)
chronic
Reduced
larval
growth
(NOAEC=
2.
9
ppb)
*
Fish
(estuarine)
acute
Very
highly
toxic
(48
hr
LC50=
23.0
ppb)
*
Fish
(estuarine)
chronic
No
data
*
Invertebrate
(freshwater)
acute
Very
highly
toxic
(96
hr
LC50=
10.
0
ppb)
*
Invertebrate
(freshwater)
chronic
Decreased
reproduction
(21
day
NOAEC=
54.0
ppb)
*
Invertebrate
(estuarine)
acute
Very
highly
toxic
(96
hr
LC50/
EC50=
0.077
ppb)
*
Invertebrate
(estuarine)
chronic
No
data
*Plants
Nodata
+
For
a
complete
listing
of
these
and
other
toxicity
studies
for
lindane,
please
see
Appendix
I.
Toxicity
to
Terrestrial
Organisms
Bird
and
mammal
overview
Lindane
is
moderately
toxic
to
birds
and
mammals
on
an
acute
exposure
basis.
Chronic
reproductive
effects
include
significant
reductions
in
egg
production,
growth
and
survival
parameters
in
birds,
and
decreased
body
weight
gain
in
mammals.
Avian
Species
(Acute
Oral,
Subacute
Dietary
and
Reproduction)
In
acute
oral
toxicity
studies
conducted
on
bobwhite
quail,
starlings,
red
winged
blackbirds
and
sparrows,
the
LD50s
for
lindane
are
122,
100,
75
and
56
mg/
kg,
respectively.
The
results
suggest
that
lindane
is
moderately
toxic
to
birds
on
an
acute
oral
basis.
Subacute
dietary
toxicity
studies
conducted
on
mallard
duck,
bobwhite
quail,
ring
necked
pheasant,
and
Japanese
quail
suggest
that
lindane
is
practically
non
toxic
to
highly
toxic,
with
LC50s
of
>5000,
882,
561
and
425
ppm,
respectively.
An
avian
reproduction
study
on
bobwhite
quail
indicated
that
significant
reductions
occurred
in
the
number
of
eggs
laid,
eggs
set,
viable
embryos,
live
3
week
embryos,
normal
hatchlings
and
14
day
old
survivors,
percentage
of
normal
hatchlings/
eggs
laid,
normal
hatchlings/
eggs
set,
normal
hatchlings/
live
3
week
embryos,
14
day
13
survivors/
eggs
set,
14
day
survivors/
normal
hatchlings,
eggshell
thickness
and
hatchling
weights.
The
No
Observable
Adverse
Effect
Concentration
(NOAEC)
and
the
Lowest
Observable
Adverse
Effect
Concentration
(LOAEC)
were
determined
to
be
80
and
320
ppm,
respectively.
Also,
an
avian
reproduction
study
using
mallard
ducks
showed
significant
reductions
in
the
number
of
viable
embryos,
live
3
week
embryos,
and
normal
hatchlings
at
the
two
highest
concentrations
(45
and
135
ppm).
The
NOAEC
and
the
LOAEC
were
determined
to
be
15
and
45
ppm,
respectively.
However,
due
to
low
hatching
success
in
the
control
group,
the
study
should
be
repeated
to
determine
if
15
ppm
is
a
valid
NOAEL
value.
The
NOAEL
value
of
15
ppm
will
be
used
in
risk
assessments
until
further
data
is
provided.
In
addition,
the
registrant
submitted
two
14
day
free
choice
avian
dietary
toxicity
studies
(400561
03
and
400561
04).
Results
suggested
that
bobwhite
quail
and
red
winged
blackbirds
were
repelled
by
treated
sorghum
seed.
These
studies
clearly
suggested
that
birds
avoided
lindane
treated
food
when
given
a
choice
and
even
in
a
no
choice
situation,
birds
did
not
readily
eat
and
were
emaciated
at
study
termination.
Mammalian
Species
(Acute
Oral
and
Reproduction)
In
toxicity
studies
conducted
on
laboratory
rats
for
the
Agency's
Health
Effects
Division
(HED),
lindane
is
moderately
toxic
to
small
mammals
on
an
acute
oral
basis
(LD50
of
88
mg/
kg).
Results
from
a
chronic
reproduction
study
indicate
reproductive
toxicity
at
a
LOAEL
of
150
ppm
(NOAEL
of
20
ppm)
with
decreased
body
weight
gain,
viability
up
to
PP4
in
both
generation
offspring
and
delayed
onset
and
completion
of
tooth
eruption
and
hair
growth
in
F2
pups
being
the
endpoints
affected.
Insects
Lindane
is
highly
toxic
to
bees
on
an
acute
contact
basis
(LD50s
ranged
from
0.20
to
0.56
µg/
bee).
Toxicity
to
Non
target
Aquatic
Animals
Freshwater
organism
toxicity
overview
Lindane
exhibits
high
to
very
high
acute
toxicity
to
freshwater
fish
(LC50
ranges
of
1.7
to
131
ppb)
and
freshwater
aquatic
invertebrates
(LC50
ranges
of
10.0
to
520
ppb).
Chronic
effects
include
reduction
in
larval
growth
in
freshwater
fish
(NOAEC=
2.9
µg/
L)
and
decreased
reproduction
in
aquatic
invertebrates
(NOAEC=
54
µg/
L).
Freshwater
fish
In
acute
toxicity
studies
conducted
on
coldwater
and
warmwater
species,
the
96
hour
LC50
values
for
the
technical
grade
material
ranged
from
1.
7
to
131
ppb,
suggesting
that
lindane
will
be
highly
to
very
highly
toxic
to
freshwater
fish
on
an
acute
basis.
Early
life
stage
toxicity
tests
conducted
on
rainbow
trout
show
that
lindane
significantly
affected
larval
growth
at
concentrations
greater
than
or
equal
to
6.
0
µg/
L.
Freshwater
invertebrates
Acute
toxicity
studies
conducted
on
a
variety
of
freshwater
aquatic
invertebrates
suggest
that
the
active
ingredient
of
lindane
is
highly
to
very
highly
toxic
on
an
acute
basis.
48
and
96
hour
LC50
or
EC50
values
ranged
from
10.0
to
520
µg/
L
in
6
studies.
A
life
cycle
toxicity
test
conducted
with
the
active
ingredient
(99.5%
ai)
on
waterflea
(Daphnia
magna)
found
a
21
day
NOAEC
of
54.0
µg/
L
and
a
LOAEC
of
110.0
µg/
L.
Decreased
reproduction
was
the
affected
endpoint
in
the
study.
14
Estuarine/
Marine
organism
toxicity
overview
Lindane
exhibits
high
to
very
high
acute
toxicity
to
estuarine/
marine
fish
and
ranges
from
moderately
to
very
highly
toxic
to
estuarine/
marine
aquatic
invertebrates.
No
data
were
submitted
to
assess
chronic
effects
to
either
estuarine/
marine
fish
or
estuarine/
marine
aquatic
invertebrates.
Estuarine/
Marine
fish
Testing
on
a
variety
of
species
resulted
in
48
and
96
hour
LC50
range
of
23.0
to
190.0
µg/
L,
which
is
considered
to
be
very
highly
to
highly
toxic
on
an
acute
basis.
No
data
on
the
chronic
effects
of
lindane
estuarine/
marine
fish
have
been
submitted.
Estuarine/
Marine
invertebrates
Acute
toxicity
testing
on
a
variety
of
estuarine/
marine
invertebrate
species
with
the
technical
product
resulted
in
48
and
96
hour
LC50
/EC50
values
ranging
from
0.
077
to
2800.0
µg/
L
which
fall
into
the
highly
to
very
highly
toxic
acute
classes
for
estuarine/
marine
invertebrates.
No
data
on
the
chronic
effects
of
lindane
have
been
submitted.
Toxicity
to
Plants
Currently,
plant
testing
is
not
required
for
pesticides
other
than
herbicides
and
fungicides
except
on
a
caseby
case
basis
(e.
g.,
labeling
bears
phytotoxicity
warnings,
incident
data
or
literature
that
demonstrates
phytotoxicity).
Because
of
the
current
low
application
rate,
lack
of
incident
data
on
plants
and
no
available
literature
suggesting
phytotoxicity,
no
plant
data
would
normally
be
required.
However,
Tier
I
plant
toxicity
studies
(850.4100
Seedling
emergence
in
10
species
and
850.5400
Aquatic
plant
toxicity
tests
in
5
species)
are
required
for
outdoor
seed
treatment
uses
(Memo
from
Denise
Keehner
re:
EFED
policy
guidance
for
eco
risk
and
drinking
water
assessments
of
seed
treatment
pesticides,
7/
30/
99).
Ecological
Incident
Data
Incidents
have
been
reported
from
the
use
of
lindane
and
are
on
the
USEPA
incident
database.
These
incidents
are
listed
in
a
table
in
Appendix
II.
The
incidents
all
involved
fish
and
lindane
was
not
the
definite
cause
for
most,
however,
one
definite
incident
was
an
accidental
spill
that
did
kill
trout.
ENVIRONMENTAL
RISK
ASSESSMENT
In
order
to
evaluate
the
potential
risk
to
aquatic
and
terrestrial
organisms
from
the
use
of
lindane,
risk
quotients
(RQs)
are
calculated
from
the
ratio
of
estimated
environmental
concentrations
(EECs)
to
generally
the
most
toxic
ecotoxicity
value
(acute)
or
no
effect
level
(chronic)
for
that
group
of
organisms.
These
RQs
are
then
compared
to
levels
of
concern
(LOCs)
used
by
OPP
to
indicate
potential
risk
to
nontarget
organisms
and
the
need
to
consider
regulatory
action.
EECs
are
based
on
the
maximum
application
rates
(worst
case)
for
selected
modeled
crop
uses
for
lindane.
Ecological
effects
data
requirements
and
assessments
for
seed
treatment
pesticides
are
normally
based
on
the
granular
risk
assessment
strategy.
The
seed
treatment
assessment
process
is
designed
to
assess
toxicological
endpoints
according
to
application
rates,
application
method,
and
soil
incorporation
depth.
Granules
(seeds)
are
assumed
to
be
consumed
by
terrestrial
wildlife,
and
exposure
may
be
limited
by
type
of
application
method.
Risk
to
Nontarget
Terrestrial
Organisms
Ecological
risks
from
seed
treatments
can
be
assessed
by
the
same
methods
used
for
granular
and
bait
products.
The
standard
assessment
is
to
calculate
the
number
of
LD50
per
square
foot
of
seeds
exposed
at
the
soil
surface,
accounting
for
incorporation
of
the
seeds
in
the
soil
(Felthousen
1977).
The
number
of
15
seeds
that
must
be
consumed
by
the
non
target
organism
to
reach
the
LD50
can
be
calculated
if
the
amount
of
active
ingredient
(AI)
on
each
seed
is
known
or
can
be
estimated.
If
the
concentration
of
active
ingredient
on
the
seed
is
known
or
can
be
estimated,
then
this
concentration
can
be
used
as
an
EEC
to
assess
risk
to
granivorous
birds
and
mammals.
For
avian
species,
this
EEC
can
be
compared
directly
to
the
dietary
LC50
value.
For
mammals,
this
EEC
can
be
compared
to
the
concentration
of
toxicant
in
food
lethal
to
50%
of
the
population,
which
is
calculated
by
dividing
the
LD50
value
by
the
fraction
of
body
weight
consumed
per
day
(McCann
1987).
Birds
and
small
mammals
actively
probe
the
soil
while
searching
for
food.
While
foraging,
they
are
known
to
ingest
soil,
both
intentionally
and
incidentally.
Beyer,
et
al.
(1994)
estimated
the
soil
content
of
the
diet
of
a
number
of
bird
and
mammal
species
to
range
from
<2%
to
30%.
Nevertheless,
soil
incorporation
will
reduce
overall
species
risk
and/
or
access
to
the
compound.
Terrestrial
assessment
The
labels
with
the
highest
rates
(lb
lindane/
100
lb
seed)
were
used
to
evaluate
potential
maximum
consumption
of
lindane
by
terrestrial
animals.
The
current
approach
uses
daily
food
intake
calculated
using
the
relationships
described
in
Nagy
(1987
as
cited
in
USEPA,
1993).
Acute
risk
quotients
(RQ)
were
then
calculated
based
on
animals
receiving
their
full
diet
from
lindane
treated
seeds
for
a
1
day
time
period
B
that
is,
mass
of
lindane
consumed
in
1
day
from
treated
seeds
RQ
=
species
specific
mass
of
lindane
required
to
reach
LD50
An
RQ
>
0.5
is
defined
as
the
level
of
possible
acute
risk.
Details
of
the
calculations
are
given
in
Appendix
II.
Results
suggest
that
there
may
be
potential
acute
and
chronic
risk
to
both
endangered
and
nonendangered
birds
and
mammals.
Smaller
birds
and
mammals
(i.
e.,
those
with
high
food
intake
rates
per
body
mass)
are
at
greater
risk
than
larger
animals.
The
calculation
pertains
to
consumption
of
food
in
dry
weight.
Seeds
used
for
planting
are
expected
to
possess
low
water
content,
thus
no
adjustments
were
made
for
wet
weight.
Aquatic
assessment
The
EFED
model
GENEEC
was
used
to
determine
aquatic
EECs.
Wheat
has
the
highest
application
rate
in
terms
of
lbs
a.
i
per
acre
(see
Table
1)
and
was
used
as
the
model
crop
scenario.
Results
of
this
assessment
are
listed
in
Appendix
II
and
the
GENEEC
output
file
is
in
Appendix
III.
An
analysis
of
the
results
suggest
that
for
estuarine/
marine
invertebrates,
high
acute
risk
(RQ
=
8.7)
may
occur
even
at
the
low
application
rates
for
seed
treatment
uses.
Restricted
use
LOCs
were
exceeded
for
estuarine/
marine
invertebrates
and
freshwater
fish.
Endangered
species
LOCs
are
exceeded
for
freshwater
fish
and
invertebrates
and
estuarine/
marine
invertebrates.
Chronic
risk
to
estuarine/
marine
organisms
could
not
be
assessed
due
to
a
lack
of
data.
Exposure
and
Risk
to
Endangered
Species
In
1983,
the
Agency
requested
a
"case
by
case"
opinion
for
a
Section
18
(emergency
use
exemption)
for
sugarcane
use
in
Florida.
Jeopardy
to
the
snail
kite,
bald
eagle
and
Florida
panther
was
found
from
potential
lindane
use.
The
Agency
agrees
with
the
jeopardy
to
the
snail
kite
due
to
reductions
to
its
food
source
(apple
snails)
from
the
sugarcane
use.
However,
even
though
lindane
exhibits
toxicity
to
birds
and
mammals,
under
the
proposed
seed
treatment
use
patterns,
low
risk
is
assumed
for
most
endangered
species
of
these
taxa
based
on
their
lifestyles,
feeding
habits
and
natural
environments.
16
When
the
regulatory
changes
recommended
in
this
IRED
are
implemented
and
the
ecological
effects
and
environmental
fate
data
are
submitted
and
accepted
by
the
Agency,
the
Reasonable
and
Prudent
Alternatives
may
need
to
be
reassessed
and
modified
based
on
the
new
information.
The
Agency
is
currently
engaged
in
a
Proactive
Conservation
Review
with
FWS
and
the
National
Marine
Fisheries
Service
under
section
7(
a)(
1)
of
the
Endangered
Species
Act.
The
objective
of
this
review
is
to
clarify
and
develop
consistent
processes
for
endangered
species
risk
assessments
and
consultations.
Subsequent
to
the
completion
of
this
process,
the
Agency
will
reassess
the
potential
effects
of
lindane
use
to
federally
listed
threatened
and
endangered
species.
At
that
time
the
Agency
will
also
consider
any
regulatory
changes
recommended
in
the
IRED
that
are
being
implemented.
Until
such
time
as
this
analysis
is
completed,
the
overall
environmental
effects
mitigation
strategy
articulated
in
this
document
and
any
County
Specific
Pamphlets
described
in
Section
IV
which
address
lindane,
will
serve
as
interim
protection
measures
to
reduce
the
likelihood
that
endangered
and
threatened
species
may
be
exposed
to
lindane
at
levels
of
concern.
RISK
CHARACTERIZATION
Summary
of
Risk
Lindane
is
a
persistent,
moderately
mobile
organochlorine
and
a
potential
endocrine
disruptor
in
birds,
mammals
and
possibly
fish.
There
is
a
possiblity
of
acute
and
chronic
reproductive
risk
from
the
use
of
lindane
treated
seed
to
endangered
and
non
endangered
avian
and
especially
mammalian
species
consuming
a
majority
of
their
body
weight
in
seed
per
day.
The
assessment
suggests
acute
risk
to
endangered
and
nonendangered
freshwater
fish
may
occur
even
at
the
low
application
rates
for
seed
treatment
uses.
However,
the
aquatic
assessment
is
based
on
the
conservative
assumption
that
100%
of
the
compound
will
disassociate
from
the
seed
surface.
Thus,
these
risks
may
be
overestimated
somewhat.
Based
on
a
screening
level
assessment,
both
surface
and
ground
water
simulations
show
that
lindane
concentrations
in
water
resulting
from
seed
treatments
may
reach
levels
of
environmental
concern
and
may
exceed
the
MCL
for
drinking
water
(0.
2ppb).
Lindane
in
water
bodies
due
to
past
uses
will
likely
remain
for
long
periods,
due
to
lindane's
extreme
persistence.
Avian
and
Mammalian
Species
Based
on
available
scientific
literature,
lindane
has
shown
adverse
endocrine
effects
in
mammals
(Raizada
et
al.
1980;
Uphouse
1987;
Cooper
et
al.
1989)
and
has
been
reported
to
disturb
male
mammalian
reproductive
functioning
(Chowdhury
et
al.,
1987;
Chowdhury
and
Gautam
1994;
Dalsenter
et
al.
1997;
Dalsenter
et
al.
1996).
Lindane
is
also
known
to
accumulate
in
fat
tissues
and
to
be
slowly
eliminated
in
milk
during
lactation
(Pompa
et
al.
1994).
Neurological
and
behavioral
alterations
are
principal
toxic
effects
of
lindane
in
animals
(Hulth
et
al.
1976;
Joy
1982).
Chakravarty
et
al.
(1986)
and
Chakravarty
and
Lahiri
(1986)
found
that
when
domestic
ducks
were
force
fed
lindane
(20
mg/
kg
of
body
weight
for
8
wks),
significant
egg
shell
thinning,
reduced
clutch
size,
and
reduced
laying
frequencies
were
observed.
They
suggested
that
lindane
induced
estradiol
insufficiency
which
causes
inhibition
of
hepatic
RNA
and
yolk
protein
synthesis,
thereby
preventing
transformation
of
moderately
differentiated
oocytes
to
mature
vitellogenic
follicles,
delaying
ovulation
and
thus
drastically
reducing
clutch
size.
Hoffman
and
Eastin
(1982)
found
that
lindane
was
teratogenic
to
mallard
ducks
only
at
doses
that
were
greater
than
five
times
the
field
level
of
application,
but
did
find
that
lindane
was
much
more
toxic
on
a
lbs
per
acre
basis
when
administered
in
oil.
However,
lindane
in
the
diet
of
laying
hens
at
100
ppm
caused
reduced
hatchability
(Whitehead
et
al.
1972)
and
at
25
ppm
the
same
effect
was
noted
in
Japanese
quail
(Dewitt
and
George
1957).
In
the
field
,
Blus
et
al.
(1985)
found
that
when
lindane
was
substituted
for
heptaclor
(HE)
for
treatment
of
seed
(Columbia
Basin
near
the
Umatilla
NWR,
in
Oregon
and
Washington
State,
USA),
lindane
did
not
produce
adverse
effects
in
birds
and
residues
were
not
detected
in
either
their
eggs
or
17
brains.
Also,
coincidental
with
the
decrease
in
HE
residues
in
Canada
geese,
mortality
decreased,
reproductive
success
improved,
and
the
population
increased
rapidly
(Blus
et
al.
1984).
There
was
no
evidence
for
either
bio
magnification
of
lindane
residues
from
treated
seeds
to
goose
tissues
or
eggs
or
for
induction
of
adverse
effects
to
avian
species.
This
may
be
due
to
the
fact
that
Canada
geese,
as
well
as
other
avian
species,
may
have
been
repelled
by
lindane
treated
seed
as
a
submitted
study
has
suggested
with
quail
and
red
winged
blackbirds.
The
registrant
submitted
two
14
day
free
choice
avian
dietary
toxicity
studies
(400561
03
and
400561
04)
using
40%
lindane.
Results
suggested
that
bobwhite
quail
and
red
winged
blackbirds
were
repelled
by
treated
sorghum
seed.
These
studies
clearly
suggested
that
birds
avoided
lindane
treated
food
when
given
a
choice
and
even
in
a
no
choice
situation,
birds
did
not
readily
eat
and
were
emaciated
at
study
termination.
Other
avian
species
may
possibly
also
show
aversion
to
lindane
treated
seed.
However,
birds
of
prey
that
consume
small
mammals
that
have
accumulated
lindane
may
be
at
risk
from
some
level
of
secondary
toxicity
from
chronic
exposure
over
time.
Also,
lindane
can
be
stored
in
the
fat
of
birds;
birds
of
prey
in
the
Netherlands
contained
up
to
89
ppm
in
their
fat
(Ulman
1972).
Earthworms
are
known
to
accumulate
lipophilic
substances
(such
as
lindane)
through
the
epidermis
and
the
intestine
(Belfroid
et
al.
1994).
In
nature,
worms
constitute
a
link
in
the
transport
of
environmental
pollutants
from
soil
to
organisms
higher
up
in
the
terrestrial
food
web.
Avian
and
mammalian
species
may
eat
worms
that
have
accumulated
lindane,
thus
providing
some
level
of
risk
to
those
species.
Also,
many
young
birds
eat
diets
rich
in
animal
foods
(including
worms),
even
though
they
may
be
strict
vegetarians
as
adults.
Many
newly
hatched
young
that
feed
themselves,
instinctively
select
protein
rich
foods
such
as
worms.
Lindane
treated
seed
will
most
likely
be
planted
in
the
spring
during,
or
just
prior
to,
breeding
season.
Higher
energy
expenditures
and
higher
caloric
need
in
mammals
during
gestation
and
lactation
imply
a
need
for
either
more
total
food
and/
or
food
with
a
higher
caloric
content.
Conditions
during
breeding
season
present
a
need
to
keep
in
close
proximity
to
the
den
and
subsequent
offspring.
Because
of
this,
mammals
living
near
fields
planted
with
lindane
treated
seed
may
not
have
the
option
of
traveling
to
non
treated
areas
and
may
in
fact
cache
these
readily
available
treated
seeds.
Most
uses
do
not
present
high
acute
risk
to
larger
seed
eating
mammals.
However,
due
to
the
compound
exhibiting
endocrine
disrupting
effects
and
being
lipophilic
and
eliminated
in
milk
during
lactation,
mammals
in
general
that
may
ingest
seeds
may
be
at
some
risk.
Milk
is
known
to
be
a
major
route
of
elimination
for
lipophilic
persistent
substances
stored
in
adipose
tissue.
The
milk:
plasma
concentration
ratio
for
lindane
indicates
a
much
more
efficient
excretion
of
the
compound
in
milk
(Dalsenter
et
al.
1997).
Milk
possesses
a
great
affinity
on
liposoluble
substances
due
to
its
high
fat
content.
The
presence
of
lindane
in
mammalian
milk
exposes
nursing
offspring
during
critical
periods
of
post
natal
development
(Dalsenter
et
al.
1997).
Small
mammals
with
high
metabolic
rates
that
dig
and
cache
seeds,
may
be
at
acute
and
especially
chronic
risk,
due
to
consumption
over
time
and
the
persistence
of
the
compound
in
soil.
Dalsenter
et
al.
(1997)
indicated
that
treatment
of
female
rats
on
day
15
of
pregnancy
with
only
a
single
dose
(30
mg
lindane/
Kg
of
body
weight)
affects
the
sexual
behavior
of
adult
male
offspring
by
altering
libido
and
by
reducing
testosterone
concentration
without
compromising
fertility.
Effects
to
offspring
may
be
due
to
the
indirect
interference
of
lindane
on
hormonal
regulation
in
males.
Pertubation
of
the
endocrine
system
during
early
stages
of
development
can
be
influenced
by
small
changes
of
hormonal
imbalance.
Aquatic
Organisms
Generally,
from
the
results
of
the
aquatic
assessment,
risks
to
aquatic
organisms
were
low.
The
highest
use
rate
(wheat)
was
modeled.
Based
on
a
Tier
I
screening
assessment
(using
GENEEC)
and
assuming
that
100%
of
the
compound
will
disassociate
from
the
seed
surface,
the
aquatic
assessment
resulted
in
risks
to
18
aquatic
organisms.
The
greatest
risk,
due
mainly
to
the
toxicity
of
the
compound,
was
to
estuarine/
marine
invertebrates
from
an
acute
exposure
(RQ=
8.
7).
There
were
no
data
available
to
assess
chronic
risk
to
these
invertebrates.
These
data
are
especially
important
since
the
compound
is
persistent
and
can
result
in
significant
bio
accumulation
(bioconcentration
factor
is
1400
times
the
ambient
water
concentration).
Acute
risk
to
endangered
and
non
endangered
freshwater
fish
may
also
occur
even
at
the
low
application
rates
for
seed
treatment
uses.
In
addition,
Petit
et
al.
(1997)
found
that
lindane
exhibited
estrogenic
activity
in
two
in
vitro
bioassays.
Thus,
lindane
may
also
be
an
endocrine
disrupting
compound
in
aquatic
species.
EFED
believes
that
a
seed
leaching
study
would
greatly
increase
certainty
regarding
a
more
realistic
estimate
of
the
amount
of
available
lindane
on
the
seed
surface.
This
in
turn
would
allow
a
refinement
of
exposure
estimates
and
environmental
concentration
values
(EECs).
However,
the
assumption
that
100%
of
the
compound
will
disassociate
from
the
seed
surface
has
likely
produced
highly
conservative
estimates
and
has
thus
overestimated
the
EEC's
and
resulting
risks.
Reproductive
and
population
effects
in
other
species
of
invertebrates
have
also
been
suggested.
Blockwell
et
al.
(1999)
found
that
populations
of
H.
azteca
(a
detritivorous
crustacean)
exposed
to
(LOAEL=
13.5
ug
lindane/
L;
NOAEC=
6.9
ug
lindane/
L)
lindane
were
significantly
(ANOVA,
p
<
0.
001;
Tukey
Kramer,
p
<0.05)
smaller
than
control
populations
in
a
35
day
chronic
study.
Reduction
in
population
growth
was
observed
and
resulted
from
a
combination
of
toxicant
effects:
disruption
of
the
reproductive
behavior
patterns
of
adult
H.
azteca
and
a
reduction
in
the
growth
of
recruited
individuals
and
consequently
their
delayed
sexual
development.
This
value
is
similar
to
the
LOAECs
produced
from
other
chronic
lindane
toxicity
studies
conducted
with
freshwater
crustaceans:
19
µg/
L
for
Daphnia
magna
in
a
64
d
study
and
8.6
µg/
L
in
a
17
week
study
conducted
with
Gammarus
fasciatus
based
on
survivorship
and
reproductive
success
(Macek
et
al.,
1976).
Furthermore,
an
LOAEC
of
9.9
ug
lindane/
L
was
generated
in
a
life
cycle
study
conducted
using
Chironomous
riparius
(Insecta)
(Taylor
et
al.
1993).
Lindane
has
also
previously
been
reported
to
reduce
juvenile
growth
of
the
European
amphipod
Gammarus
pulex
(L.)
at
6.1
µg/
L
in
a
14
d
study
(Blockwell
et
al.
1996).
However,
data
shows
that
concentrations
of
lindane
above
2.
5
µg/
L
(found
in
Lake
Michigan
tributary
stream)
were
not
reported
as
occurring
in
any
aquatic
system
tested
(ATSDR
1997).
Incidents
have
been
reported
from
the
use
of
lindane
and
are
in
the
EPA
incident
database.
An
incident
classified
as
"highly
probable"
was
reported
as
killing
hundreds
of
trout
on
a
tree
farm
in
Watauga,
North
Carolina
after
a
spill
close
to
a
nearby
stream.
However,
no
aquatic
incidents
have
been
reported
as
having
occurred
under
normal
use
conditions
of
seed
treatment
under
soil
incorporated
use
patterns.
Endocrine
Disruption
EPA
is
required
under
the
Federal
Food,
Drug,
and
Cosmetic
Act
(FFDCA),
as
amended
by
the
Food
Quality
Protection
Act
(FQPA),
to
develop
a
screening
program
to
determine
whether
certain
substances
(including
all
pesticide
active
and
other
ingredients)
"may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
the
recommendations
of
its
Endocrine
Disrupting
Screening
and
Testing
Advisory
Committee
(EDSTAC),
EPA
determined
that
there
was
scientific
basis
for
including,
as
part
of
the
program,
the
androgen
and
thyroid
hormone
systems,
in
addition
to
the
estrogen
hormone
system.
EPA
also
adopted
EDSTAC's
recommendation
that
the
Program
include
evaluations
of
potential
effects
in
wildlife.
For
pesticidal
chemicals,
EPA
will
use
FIFRA
and,
to
the
extent
that
effects
in
wildlife
may
help
determine
whether
a
substance
may
have
an
effect
in
humans,
FFDCA
has
authority
to
require
the
wildlife
evaluations.
As
the
science
develops
and
resources
allow,
screening
of
additional
hormone
systems
may
be
added
to
the
Endocrine
Disruptor
Screening
Program
(EDSP).
19
Based
on
available
scientific
literature,
lindane
has
characteristics
of
an
endocrine
disrupting
compound.
The
compound
exhibits
effects
on
birds,
mammals
and
possibly
fish.
As
stated
previously,
effects
included
disruption
in
male
reproductive
behavior
and
functioning
in
mammals
(LD50=
88
mg/
kg
with
levels
of
only
30
mg/
kg
resulting
in
effects),
eggshell
thinning
possibly
from
estrogen
deficiency
in
female
birds,
and
estradiol
insufficiency
which
may
cause
a
delay
in
ovulation
resulting
in
a
drastic
reduction
in
clutch
size
in
birds
(NOAEL/
LOAEC=
80/
320
ppm
with
calculated
EEC
levels
of
51.5
to
206.2
ppm
resulting
in
a
possibility
of
effects).
In
the
submitted
avian
reproduction
study
using
the
mallard
duck
(MRID
448671
01),
thyroid
weights
for
males
in
the
135
ppm
test
concentration
were
significantly
higher
than
those
measured
in
the
control.
Histopathology
revealed
microscopic
lesions
in
the
thyroid
glands
consisting
of
thyroid
follicular
distension
and
coalescence,
follicular
hypertrophy
and
follicular
hyperplasia.
These
lesions
were
more
apparent
at
the
135
ppm
than
at
45
ppm.
Analysis
of
the
gonads
of
either
sex
were
unremarkable
with
the
exception
of
the
possibility
of
reduced
spermatogenesis
in
the
group
receiving
45
ppm.
Exposure
of
mammalian
neonates
to
lindane
during
lactation
induces
reproductive
hazards
to
male
offspring
rats
which
are
detectable
at
adulthood.
Based
on
all
these
data,
EFED
recommends
that
when
appropriate
screening
and
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
lindane
be
subjected
to
more
definitive
testing
to
better
characterize
effects
related
to
its
endocrine
disruptor
activity
under
the
current
use
pattern.
Presence
in
the
Environment
Lindane,
as
well
as
other
HCH
isomers,
do
not
naturally
occur
in
the
environment.
Once
released
into
the
environment,
lindane
can
partition
into
various
environmental
media.
Because
of
long
range
transport,
lindane
has
been
detected
in
air,
surface
water,
groundwater,
sediment,
soil,
ice,
snowpack,
fish,
wildlife
and
humans.
HCH
isomers
(mainly
and
)
were
the
major
organochlorine
insecticide
detected
in
arctic
air,
snow
and
seawater
(Barrie
et
al.
1991).
The
Arctic
is
considered
a
"sink"
for
persistent
organic
pollutants.
Once
in
the
Arctic,
lindane
bio
accumulates
in
the
food
chain
due
to
its
high
lipid
solubility.
Lindane
is
bio
concentrated
rapidly
in
microrganisms,
invertebrates,
fish,
birds
and
mammals,
however
biotransformation
and
elimination
are
relatively
rapid
when
exposure
is
discontinued
(WHO
1991).
Lindane
is
strongly
adsorbed
on
soils
that
contain
large
amounts
of
organic
matter,
however
it
can
leach
with
water
from
rainfall
or
artificial
irrigation.
Lindane
sorbed
to
soil
can
get
into
the
atmosphere
either
by
wind
erosion
of
the
soil
particulates
or
by
volatilization.
Volatilization
seems
to
be
an
important
route
of
dissipation
under
higher
temperature
conditions
such
as
those
occurring
in
tropical
regions
(WHO
1991).
Levels
of
lindane
in
the
atmosphere
seem
to
be
seasonal
and
temperature
dependent,
with
the
highest
air
concentrations
in
the
summer
and
lowest
during
winter,
as
would
be
expected
from
agricultural
uses
(Whitmore
et
al.,
1994).
Removal
of
foliar
and
broadcast
type
applications
and
uses
in
favor
of
low
rate
seed
treatments
will
most
likely
limit
the
amount
of
available
lindane
for
release
into
the
environment.
However,
Waite
et
al.
(1998)
did
find
that
release
of
lindane
to
the
atmosphere
begins
within
the
first
week
the
treated
seed
is
sown.
Most
recently,
Waite
et
al.
(2001)
found
that
between
30%
(in
1997)
and
12%
(in
1998)
of
the
lindane
applied
to
canola
fields
(as
treated
seed)
was
lost
through
volatilization
that
began
immediately
after
planting.
Lindane
is
more
soluble
in
water
than
most
other
OC
compounds,
therefore
it
has
a
greater
possibility
of
remaining
in
the
water
column.
Agricultural
run
off
is
likely
the
major
contamination
route
of
lindane
to
surface
water.
The
three
main
transport
pathways
for
atmospheric
input
to
surface
waters
are
wet
deposition,
dry
deposition
and
gas
exchange
across
the
air
water
interface,
although
evaporative
loss
from
surface
water
is
not
considered
significant.
Apart
from
atmospheric
deposition
and
surface
run
off,
point
source
discharges
are
also
contributors
of
surface
water
contamination.
In
Canada,
run
off
from
canola
fields
was
reported
to
contaminate
surface
water
with
maximum
concentrations
of
0.011
ppb
and
0.
004
20
ppb
for
lindane
and
HCH,
respectively
(Donald
et
al.,
1997).
As
stated
previously,
both
surface
and
ground
water
simulations,
based
on
a
screening
level
assessment,
show
that
lindane
concentrations
in
water
resulting
from
seed
treatment
may
reach
levels
of
environmental
concern
and
may
exceed
the
MCL
for
drinking
water
(0.2
ppb).
Lindane
in
water
bodies
due
to
past
uses
will
likely
remain
for
long
periods,
due
to
lindane's
extreme
persistence.
Persistence
and
long
range
transport
of
HCH
isomers
were
also
reflected
in
monitoring
data
and
various
modeling
efforts.
The
most
common
hexachlorocyclohexane
isomers
found
in
the
environment
are
lindane
(
),
,
and
HCHs,
with
HCH
as
the
predominant
isomer
in
air
and
ocean
water
and
HCH
the
predominant
isomer
in
soils,
animal
tissues
and
fluids
(Willett
et
al.,
1998).
Recent
data
suggest
that
the
declines
of
HCH
isomer
concentrations
in
the
environment
have
resulted
from
reduced
use
of
technical
HCH,
especially
in
Asian
countries
(Iwata
et
al.,
1993).
However,
Oehme
et
al.,
(1995)
have
suggested
that
while
there
are
some
indications
that
total
HCH
in
Arctic
air
has
declined,
mean
levels
of
lindane
have
increased
slightly,
which
likely
reflects
the
increase
in
lindane
use
in
northern
hemisphere
after
the
ban
of
technical
HCH
was
imposed.
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25
Appendix
I:
Ecological
Effects
Data
Ecological
toxicity
studies
required
by
the
Agency
for
the
registration/
re
registration
of
a
pesticide,
and
the
rational
behind
these
requirements,
are
listed
in
40
CFR
158.
The
following
studies
submitted
by
the
registrant
were
used
to
develop
an
ecological
toxicity
assessment
for
lindane.
Toxicity
to
Terrestrial
Animals
Birds,
Acute
and
Subacute
Avian
Acute
Oral
Toxicity
Species
%ai
LD50
(mg/
kg)
Toxicity
Category
Acc
No.
Author/
Year
Study
Classification
1
Bobwhite
quail
(Colinus
virginianus)
95.5
122
Moderately
toxic
00263944
Bio
life,
1986
Core
Red
winged
BB
(Agelaius
phoeniceus)
Tech
75
Moderately
toxic
00020560,
Schafer,
1972
Supplemental
Starling
(Sturnus
vulgaris)
Tech
100
Moderately
toxic
00020560,
Schafer,
1972
Supplemental
House
Sparrow
(Passer
domesticus)
Tech
56
Moderately
toxic
00020560,
Schafer,
1972
Supplemental
Common
Grackle
(Quiscalus
quisula)
Tech
>100
Moderately
toxic
00020560,
Schafer,
1972
Supplemental
Mallard
Duck
(Anas
platyrhynchos)
25
2000
practically
non
toxic
00160000
Hudson
et
al,
1984
Supplemental
1
Core
(study
satisfies
guideline).
Since
the
LD50s
using
the
technical
grade
range
from
56
to
122
mg/
kg,
lindane
is
considered
to
be
moderately
toxic
to
avian
species
on
an
acute
oral
basis.
The
guideline
(71
1)
is
fulfilled
(ACC#
00263944).
Avian
Subacute
Dietary
Toxicity
Species
%ai
5
Day
LC50
(ppm)
1
Toxicity
Category
Acc
No.
Author/
Year
Study
Classification
Mallard
duck
(Anas
platyrhynchos)
>95
>5000
prac.
non
toxic
00022923
Hill
et
al,
1975
core
Northern
bobwhite
quail
(Colinus
virginianus)
>95
882
moderately
toxic
00022923
Hill
et
al,
1975
core
Ring
necked
pheasant
(Phasianus
colchicus)
>95
561
moderately
toxic
00022923
Hill
et
al,
1975
core
Japanese
quail
(Coturnix
japonica)
>95
425
highly
toxic
00022923
Hill
et
al,
1975
supplemental
1
Test
organisms
observed
an
additional
three
days
while
on
untreated
feed.
Since
the
LC50
falls
in
the
range
of
425
to
>5000
ppm,
lindane
is
considered
to
be
highly
to
practically
non
toxic
to
avian
species
on
a
subacute
dietary
basis.
The
guideline
(71
2)
is
fulfilled.
(ACC#
00022923).
26
In
addition,
the
registrant
submitted
two
14
day
free
choice
avian
dietary
toxicity
studies
(MRIDs
400561
03
and
400561
04).
Results
suggested
that
bobwhite
quail
and
red
winged
blackbirds
in
a
laboratory
environment
were
repelled
by
treated
sorghum
seed.
When
given
a
choice
and
even
in
a
no
choice
situation,
these
birds
did
not
readily
eat
and
were
emaciated
at
study
termination.
Birds,
Chronic
Avian
Reproduction
Species/
Study
Duration
%ai
NOAEC/
LOAE
C
1
(ppm)
LOAEC
Endpoints
MRID
No.
Author/
Year
Study
Classification
Northern
bobwhite
quail
(Colinus
virginianus)
99.8
80/
320
egg
production,
survival,
eggshell
thickness
and
hatchling
wt.
448122
01
Dreumel
and
Heijink,
1999
Core
Mallard
duck
(Anas
platyrhynchos)
99.8
15/
45
viable
embryos,
live
3wk
embryos
and
normal
hatchlings
448671
01
Dreumel
and
Heijink,
1999
Supplemental
1
NOAEC
=
No
Observed
Effect
Concentration;
LOAEC
=
Lowest
Observed
Effect
Concentration,
ND
=
Not
Determined
The
guideline
(71
4)
is
not
fulfilled
(MRID
448122
01
and
448671
01).
The
avian
reproduction
study
(Mallard
duck)
needs
to
be
repeated.
Although
the
submitted
study
(MRID
448671
01)
was
classified
as
being
supplemental
due
to
guideline
deviations
as
well
as
the
low
hatching
success
in
the
control
group,
the
study
should
be
repeated
to
determine
if
15
ppm
is
a
valid
NOAEL
value.
The
NOAEL
value
of
15
ppm
will
be
used
in
risk
assessments
until
further
data
is
provided.
Mammals,
Acute
and
Chronic
In
most
cases,
rat
or
mouse
toxicity
values
obtained
from
the
Agency's
Health
Effects
Division
(HED)
substitute
for
wild
mammal
testing.
These
toxicity
values
are
reported
below.
Mammalian
Toxicity:
Acute
and
Chronic
Species
%ai
Test
Type
Toxicity
Value
Year
MRID/
Acc
No.
Laboratory
rat
(Rattus
norvegicus)
technical
LD50
88
(males);
91
(females);
moderately
toxic
Gaines
1969.
Tox.
&
Appl.
Pharm.
14:
515
534
00049330
Laboratory
rat
(Rattus
norvegicus)
99.5
2
Generation
reproduction
NOAEL=
20
ppm
LOAEL=
150
ppm
1991
422461
01
27
Insects
Nontarget
Insect
Acute
Contact
Toxicity
Species
%ai
LD50
(g/
bee)
Toxicity
Category
ACC
No.
Author/
Year
Study
Classification
Honey
bee
(Apis
mellifera)
Honey
bee
(Apis
mellifera)
technical
technical
0.56
0.20
Highly
toxic
Highly
toxic
00036935,1975
05001991,1978
core
core
The
results
indicate
that
lindane
is
highly
toxic
to
bees
on
an
acute
contact
basis.
The
guideline
(141
1)
is
fulfilled.
(ACC#
00036935
and
05001991).
Terrestrial
invertebrates
Nontarget
Terrestrial
Invertebrate
Acute
Toxicity
Species
%ai
LC50
(ppb)
Toxicity
Category
ACC
No.
Author/
Year
Study
Classification
Sowbug
(Asellus
brevicaudus)
99
10.0
Moderately
toxic
400946
02
Supplemental
The
results
indicate
that
lindane
is
moderately
toxic
to
terrestrial
invertebrates
on
an
acute
dietary
basis.
There
are
no
guideline
requirements
for
terrestrial
invertebrates
(MRID#
400946
02).
Toxicity
to
Aquatic
Organisms
Freshwater
Fish,
Acute
Freshwater
Fish
Acute
Toxicity
Species
%ai
96
hour
LC50
(ppb)
Toxicity
Category
MRID/
Acc
No.
Study
Classification
Goldfish
(Carassius
auratus)
99
131.0
Highly
toxic
400946
02
Supplemental
Rainbow
trout
(Oncorhynchus
mykiss)
99
18.0
Very
highly
toxic
400980
01
Core
Brown
trout
(Salmo
trutta)
99
1.7
Very
highly
toxic
400946
02
Core
Bluegill
sunfish
(Lepomis
macrochirus)
99
25.0
Very
highly
toxic
400980
01
Core
Black
bullhead
(Ictalurus
melas)
99
64.0
Very
highly
toxic
400946
02
Core
Brown
trout
(Salmo
trutta)
99
22.0
Very
highly
toxic
400980
01
Core
Freshwater
Fish
Acute
Toxicity
Species
%ai
96
hour
LC50
(ppb)
Toxicity
Category
MRID/
Acc
No.
Study
Classification
28
Channel
catfish
(Ictalurus
punctatus)
99
44.0
Very
highly
toxic
400946
02
Core
Yellow
perch
(Perca
flavescens)
99
68.0
Very
highly
toxic
400946
02
Core
Fathead
minnow
(Pimephales
promelas)
99
77.0
Very
highly
toxic
400980
01
Core
Fathead
minnow
(Pimephales
promelas)
99
67.0
Very
highly
toxic
400980
01
Core
Lake
trout
(Salvelinus
namaycush)
99
32.0
Very
highly
toxic
400946
02
Core
Lake
trout
(Salvelinus
namaycush)
99
24.0
Very
highly
toxic
400980
01
Supplemental
Carp
(Cyprinus
carpio)
99
90.0
Very
highly
toxic
400946
02
Supplemental
Coho
salmon
(Oncorhynchus
kisutch)
99
23.0
Very
highly
toxic
400946
02
Core
Green
sunfish
(Lepomis
cyanellus)
99
70.0
Very
highly
toxic
400980
01
Core
Largemouth
bass
(Micropterus
salmoides)
99
32.0
Very
highly
toxic
400946
02
Core
MRID
400946
02=
Macek
and
McAllister.
1970.
Insecticide
susceptibility
of
some
common
fish
family
representatives.
Trans.
Amer.
Fish
Soc.
99:
20
27.
Because
the
96
hour
LC50
for
the
technical
grade
material
falls
in
the
range
of
1.7
to
131
ppb,
lindane
is
considered
to
be
highly
to
very
highly
toxic
to
freshwater
fish
on
an
acute
basis.
The
guideline
(72
1)
is
fulfilled
(MRID/
Acc#
400946
02
and
400980
01).
Freshwater
Fish,
Chronic
Freshwater
Fish
Early
Life
Stage
Toxicity
Under
Flow
through
Conditions
Species
%ai
NOAEC/
LOAEC
(ppb)
MATC
1
(ppb)
Endpoints
Affected
MRID
No.
Study
Classification
Rainbow
trout
(Oncorhynchus
mykiss)
99.5
2.
9/
6.
0
4.2
Larval
wet
wt.
444054
01
and
400561
05
Supplemental
1
MATC
=
Maximum
Allowed
Toxic
Concentration,
defined
as
the
geometric
mean
of
the
NOAEC
and
LOAEC.
29
This
study
was
scientifically
sound
but
did
not
fulfill
guideline
requirements.
The
study
contained
enough
information
that
if
repeated,
would
not
add
further
information.
The
guideline
(72
4)
is
fulfilled
(MRID#
444054
01
and
400561
05).
The
data
indicate
that
lindane
significantly
affected
larval
growth
at
concentrations
equal
to
or
greater
than
6.0
ppb.
In
a
memo
dated
8/
27/
98,
after
review
by
the
EFED
Aquatic
Biology
Technical
Team,
it
was
concluded
that
the
study
produced
a
valid
NOAEC
and
LOAEC
even
with
the
problems
encountered
during
the
course
of
this
study,
thus,
even
though
the
study
was
classified
as
being
supplemental,
the
study
does
not
need
to
be
repeated.
Freshwater
Invertebrates,
Acute
Freshwater
Invertebrate
Acute
Toxicity
Species
%
ai
48
hour
LC50/
EC50
(ppb)
Toxicity
Category
MRID/
Acc
No.
Study
Classification
Waterflea
(Daphnia
pulex)
99
460.0
Highly
toxic
400946
02
Core
Scud
(Gammarus
fasciatus)
99
10.0
(96
hr)
Very
highly
toxic
400946
02
Supplemental
Scud
(Gammarus
fasciatus)
100
88.0
(96
hr)
Very
highly
toxic
400946
02
Supplemental
Stonefly
(Pteronarcys
californica)
99
1.0
(96
hr)
Very
highly
toxic
400980
01
Core
Stonefly
(Pteronarcys
californica)
99
4.5
(96
hr)
Very
highly
toxic
400980
01
Core
Waterflea
(Simocephalus
serrulatus)
99
520.0
Highly
toxic
400946
02
Supplemental
Because
the
LC50/
EC50
of
the
TGAI
ranges
from
1.
0
to
520
ppb,
lindane
is
considered
to
be
very
highly
to
highly
toxic
to
aquatic
invertebrates
on
an
acute
basis.
The
guideline
(72
2)
is
fulfilled
(MRID#
400946
02).
Freshwater
Invertebrate,
Chronic
Freshwater
Aquatic
Invertebrate
Life
Cycle
Toxicity
Species
%
ai
21
day
NOAEC/
LOAEC
(ppb)
MATC
1
(ppb)
Endpoints
Affected
MRID
No.
Study
Classification
Waterflea
(Daphnia
magna)
99.5
54/
110
77
Reproduction
444054
02/
400561
06
Supplemental
1
Maximum
Allowed
Toxic
Concentration,
defined
as
the
geometric
mean
of
the
NOAEC
and
LOAEC.
The
data
indicate
that
lindane
significantly
reduced
reproduction
at
concentrations
equal
to
or
greater
than
110
ppb.
This
study
was
scientifically
sound
but
did
not
fulfill
guideline
(72
4)
requirements
(MRID#
444054
02/
400561
06).
The
study
contained
enough
information
that
if
repeated,
would
not
add
further
information.
30
Estuarine
and
Marine
Fish,
Acute
Estuarine/
Marine
Fish
Acute
Toxicity
Species
%ai
96
hour
LC50
(ppb)
Toxicity
Category
MRID
No.
Study
Classification
Pinfish
(Lagodon
rhomboides)
100
31.0
Very
highly
toxic
402284
01
Supplemental
Sheepshead
minnow
(Cyprinodon
variegatus)
100
100.0
Very
highly
toxic
402284
01
Supplemental
Longnose
killfish
(Fundulus
similis)
100
190.0
(48
hr)
Highly
toxic
402284
01
Supplemental
Spot
(Leiostomus
xanthurus)
100
23.0
(48
hr)
Very
highly
toxic
402284
01
Supplemental
Striped
mullet
(Mugil
cephalus)
100
23.0
(48
hr)
Very
highly
toxic
402284
01
Supplemental
Since
the
48
and
96
hr
LC50s
range
from
23.0
to
190.0
ppb,
lindane
is
considered
to
be
very
highly
toxic
to
highly
toxic
to
estuarine/
marine
fish
on
an
acute
basis.
The
data
above,
taken
together,
fulfill
the
guideline
(72
3a)
requirements
(MRID
402284
01).
Estuarine
and
Marine
Fish,
Chronic
No
data
were
submitted.
Estuarine
and
Marine
Invertebrates,
Acute
Estuarine/
Marine
Invertebrate
Acute
Toxicity
Species
%ai.
96
hour
LC50/
EC50
(ppb)
Toxicity
Category
MRID/
Acc
No.
Study
Classification
Eastern
oyster
(spat)
(Crassostrea
virginica)
100
240
Highly
toxic
402284
01
Core
Eastern
oyster
(Emb/
Larval)
(Crassostrea
virginica)
99.5
2820
(48hr
EC50)
Moderately
toxic
00264036/
443555
01
Supplemental
Brown
shrimp
(Penaeus
aztecus)
100
0.22
(48
hr
EC50)
Very
highly
toxic
402284
01
Supplemental
Mysid
(Mysidopsis
bahia)
100
6.3
Very
highly
toxic
402284
01
Supplemental
Grass
shrimp
(Palaemonetes
vulgaris)
100
4.4
Very
highly
toxic
402284
01
Supplemental
Seed
Shrimp
(Cypridopsis
vidua)
99
3.2
(48
hr
LC50)
Very
highly
toxic
400946
02
Supplemental
Pink
Shrimp
(Penaeus
duorarum)
100
0.077
Very
highly
toxic
402284
01
Supplemental
31
Because
the
LC50s
range
from
0.
077
to
2820
ppb,
the
TGAI
of
lindane
is
considered
very
highly
to
moderately
toxic
to
estuarine/
marine
invertebrates
on
an
acute
basis.
The
guideline
(72
3b
and
72
3c)
is
fulfilled
(MRID/
Acc#
s
264036,
400946
02,
and
402284
01).
Estuarine
and
Marine
Invertebrate,
Chronic
No
data
were
submitted.
Toxicity
to
Plants
Currently,
plant
testing
is
not
required
for
pesticides
other
than
herbicides
and
fungicides
except
on
a
caseby
case
basis
(e.
g.,
labeling
bears
phytotoxicity
warnings,
incident
data
or
literature
that
demonstrates
phytotoxicity).
Because
of
the
current
use
pattern
(incorporated
seed
treatment),
low
application
rate,
lack
of
incident
data
on
plants
and
no
available
literature
suggesting
phytotoxicity,
no
plant
data
are
required.
32
Appendix
II:
Risk
Assessment
A
means
of
integrating
the
results
of
exposure
and
ecotoxicity
data
is
called
the
quotient
method.
For
this
method,
risk
quotients
(RQs)
are
calculated
by
dividing
exposure
estimates
by
ecotoxicity
values,
both
acute
and
chronic.
RQ
=
EXPOSURE/
TOXICITY
RQs
are
then
compared
to
OPP's
levels
of
concern
(LOCs).
These
LOCs
are
criteria
used
by
OPP
to
indicate
potential
risk
to
nontarget
organisms
and
the
need
to
consider
regulatory
action.
The
criteria
indicate
that
a
pesticide
used
as
directed
has
the
potential
to
cause
adverse
effects
on
nontarget
organisms.
LOCs
currently
address
the
following
risk
presumption
categories:
(1)
acute
high
potential
for
acute
risk
is
high,
regulatory
action
may
be
warranted
in
addition
to
restricted
use
classification
(2)
acute
restricted
use
the
potential
for
acute
risk
is
high,
but
this
may
be
mitigated
through
restricted
use
classification
(3)
acute
endangered
species
the
potential
for
acute
risk
to
endangered
species
is
high,
regulatory
action
may
be
warranted,
and
(4)
chronic
risk
the
potential
for
chronic
risk
is
high,
regulatory
action
may
be
warranted.
Currently,
EFED
does
not
perform
assessments
for
chronic
risk
to
plants,
acute
or
chronic
risks
to
nontarget
insects,
or
chronic
risk
from
granular/
bait
formulations
to
mammalian
or
avian
species.
The
ecotoxicity
test
values
(i.
e.,
measurement
endpoints)
used
in
the
acute
and
chronic
risk
quotients
are
derived
from
the
results
of
required
studies.
Examples
of
ecotoxicity
values
derived
from
the
results
of
short
term
laboratory
studies
that
assess
acute
effects
are:
(1)
LC50
(fish
and
birds)
(2)
LD50
(birds
and
mammals)
(3)
EC50
(aquatic
plants
and
aquatic
invertebrates)
and
(4)
EC25
(terrestrial
plants).
An
example
of
a
toxicity
test
effect
level
derived
from
the
results
of
long
term
laboratory
studies
that
assess
chronic
effects
is:
(1)
NOAEC
(birds,
fish
and
aquatic
organisms).
Risk
presumptions,
along
with
the
corresponding
RQs
and
LOCs
are
tabulated
below:
Risk
Presumptions
for
Terrestrial
Animals
Risk
Presumption
RQ
LOC
Birds
Acute
High
Risk
EEC
1
/LC50
or
LD50/
sq
ft
or
LD50/
day
3
0.5
Acute
Restricted
Use
EEC/
LC50
or
LD50/
sq
ft
or
LD50/
day
(or
LD50
<
50
mg/
kg)
0.
2
Acute
Endangered
Species
EEC/
LC50
or
LD50/
sq
ft
or
LD50/
day
0.
1
Chronic
Risk
EEC/
NOAEC
1
Wild
Mammals
Acute
High
Risk
EEC/
LC50
or
LD50/
sq
ft
or
LD50/
day
0.
5
Acute
Restricted
Use
EEC/
LC50
or
LD50/
sq
ft
or
LD50/
day
(or
LD50
<
50
mg/
kg)
0.
2
Acute
Endangered
Species
EEC/
LC50
or
LD50/
sq
ft
or
LD50/
day
0.
1
Chronic
Risk
EEC/
NOAEC
1
1
abbreviation
for
Estimated
Environmental
Concentration
(ppm)
on
avian/
mammalian
food
items
2
mg/
ft
2
3
mg
of
toxicant
consumed/
day
LD50
*
wt.
of
bird
LD50
*
wt.
of
bird
33
Risk
Presumptions
for
Aquatic
Animals
Risk
Presumption
RQ
LOC
Acute
High
Risk
EEC
1
/LC50
or
EC50
0.
5
Acute
Restricted
Use
EEC/
LC50
or
EC50
0.
1
Acute
Endangered
Species
EEC/
LC50
or
EC50
0.
05
Chronic
Risk
EEC/
MATC
or
NOAEC
1
1
EEC
=
(ppm
or
ppb)
in
water
Risk
Presumptions
for
Plants
Risk
Presumption
RQ
LOC
Terrestrial
and
Semi
Aquatic
Plants
Acute
High
Risk
EEC
1
/EC25
1
Acute
Endangered
Species
EEC/
EC05
or
NOAEC
1
Aquatic
Plants
Acute
High
Risk
EEC
2
/EC50
1
Acute
Endangered
Species
EEC/
EC05
or
NOAEC
1
1
EEC
=
lbs
ai/
A
2
EEC
=
(ppm/
ppb)
in
water
Terrestrial
Exposure
Assessment
The
terrestrial
exposure
assessment
for
lindane
seed
treatment
use
is
based
on
the
calculation
of
the
amount
of
seeds
that
a
bird
must
ingest
to
receive
a
lethal
LD50
dose
compared
to
the
amount
of
seeds
a
bird
could
ingests
(if
the
diet
consisted
of
only
lindane
treated
seeds).
Other
Factors
Affecting
Risk
Only
two
bird
species
are
usually
required
to
be
tested
B
one
waterfowl
species
and
one
upland
gamebird
species
B
under
the
Fish
and
Wildlife
Data
Requirements
listed
in
CFR
158.
There
is
a
great
deal
of
uncertainty
associated
with
extrapolating
from
the
acute
oral
and
subacute
dietary
data
from
two
species
to
the
large
numbers
of
bird
species
associated
with
agricultural
areas.
Field
surveys
indicate
that
a
large
variety
of
birds
are
associated
with
these
areas,
including
a
multitude
of
songbirds
and
many
others.
Waterfowl
are
also
likely
to
be
present
in
these
regions.
As
the
EFED
ecological
database
indicates
that
songbirds
tend
to
be
more
sensitive
than
the
two
required
test
species,
using
the
maximum
estimated
environmental
concentration
to
calculate
risk
helps
to
compensate
for
this
uncertainty
in
the
toxicity
data.
However,
in
this
case,
actual
acute
data
are
available
for
songbirds
(Sparrow
LD50=
56
mg/
kg
and
Redwinged
blackbird
LD50=
75
mg/
kg).
The
lack
or
small
number
of
reported
incidents
involving
birds
or
mammals
does
not
prove
that
animals
are
not
dying
from
pesticide
exposure.
Finding
dead
animals
in
the
field
is
difficult,
even
when
experienced
field
biologists
are
searching
treated
fields.
Reporting
of
incident
data
is
still
rather
accidental,
and
only
carefully
designed
field
studies
can
confidently
indicate
the
likelihood
of
field
kill
incidents
occurring.
34
ECOLOGICAL
INCIDENTS
SUMMARY
The
number
of
documented
kills
in
the
Ecological
Incident
Information
System
is
believed
to
be
but
a
very
small
fraction
of
total
mortality
caused
by
pesticides.
Mortality
incidents
must
be
seen,
reported,
investigated,
and
have
investigation
reports
submitted
to
EPA
to
have
the
potential
for
entry
into
the
database.
Incidents
often
are
not
seen,
due
to
scavenger
removal
of
carcasses,
decay
in
the
field,
or
simply
because
carcasses
may
be
hard
to
see
on
many
sites
and/
or
few
people
are
systematically
looking.
Poisoned
birds
may
also
move
off
site
to
less
conspicuous
areas
before
dying.
Incidents
seen
may
not
get
reported
to
appropriate
authorities
capable
of
investigating
the
incident
because
the
finder
may
not
know
of
the
importance
of
reporting
incidents,
may
not
know
who
to
call,
may
not
feel
they
have
the
time
or
desire
to
call,
may
hesitate
to
call
because
of
their
own
involvement
in
the
kill,
or
the
call
may
be
long
distance
and
discourage
callers,
for
example.
Incidents
reported
may
not
get
investigated
if
resources
are
limited
or
may
not
get
investigated
thoroughly,
with
residue
and
ChE
analyses,
for
example.
Also,
if
kills
are
not
reported
and
investigated
promptly,
there
will
be
little
chance
of
documenting
the
cause,
since
tissues
and
residues
may
deteriorate
quickly.
Reports
of
investigated
incidents
often
do
not
get
submitted
to
EPA,
since
reporting
by
states
is
voluntary
and
some
investigators
may
believe
that
they
don't
have
the
resources
to
submit
incident
reports
to
EPA.
Incident
reports
submitted
to
EPA
since
approximately
1994
have
been
tracked
by
assignment
of
I#
s
in
an
Incident
Data
System
(IDS),
microfiched,
and
then
entered
to
a
second
database,
the
Ecological
Incident
Information
System
(EIIS).
This
second
database
has
some
85
fields
for
potential
data
entry.
An
effort
has
also
been
made
to
enter
information
to
EIIS
on
incident
reports
received
prior
to
establishment
of
current
databases.
Although
many
of
these
have
been
added,
the
system
is
not
yet
a
complete
listing
of
all
incident
reports
received
by
EPA.
Incident
reports
are
not
received
in
a
consistent
format
(e.
g.,
states
and
various
labs
usually
have
their
own
formats),
may
involve
multiple
incidents
involving
multiple
chemicals
in
one
report,
and
may
report
on
only
part
of
a
given
incident
investigation
(e.
g.,
residues).
While
some
progress
has
been
made
in
recent
years,
both
in
getting
incident
reports
submitted
and
entered,
there
has
never
been
the
level
of
resources
assigned
to
incidents
that
there
has
been
to
the
tracking
and
review
of
laboratory
toxicity
studies,
for
example.
This
adds
to
the
reasons
cited
above
for
why
EPA
believes
the
documented
kills
are
but
a
fraction
of
total
mortality
caused
by
lindane
and
other
highly
toxic
pesticides.
Incidents
entered
into
EIIS
are
categorized
into
one
of
several
certainty
levels:
highly
probable,
probable,
possible,
unlikely,
or
unrelated.
In
brief,
"highly
probable"
incidents
usually
require
carcass
residues,
substantial
ChE
inhibition
in
avian
and/
or
mammalian
species,
and/
or
clear
circumstances
regarding
the
exposure.
"Probable"
incidents
include
those
where
residues
were
not
available
and/
or
circumstances
were
less
clear
than
for
"highly
probable."
"Possible"
incidents
include
those
where
multiple
chemicals
may
have
been
involved
and
it
is
not
clear
what
the
contribution
was
of
a
given
chemical.
The
"unlikely"
category
is
used,
for
example,
where
a
given
chemical
is
practically
nontoxic
to
the
category
of
organism
killed
and/
or
the
chemical
was
tested
for
but
not
detected
in
samples.
"Unrelated"
incidents
are
those
that
have
been
confirmed
to
be
not
pesticide
related.
Incidents
entered
into
the
EIIS
are
also
categorized
as
to
use/
misuse.
Unless
specifically
confirmed
by
a
state
or
federal
agency
to
be
misuse,
or
there
was
very
clear
misuse
such
as
intentional
baiting
to
kill
wildlife,
incidents
would
not
typically
be
considered
misuse.
Data
entry
personnel
often
do
not
have
a
copy
of
the
specific
label
used
in
a
given
application,
and
would
not
usually
be
able
to
detect
a
variety
of
labelspecific
violations,
for
example.
35
Incidents
have
been
reported
from
the
use
of
lindane
and
are
on
the
EPA
incident
database.
These
incidents
are
listed
in
the
table
below:
Incident
#
Date
State
Organism
Tissue
analysis
Tissue/
soil
Concentration
Use
Site
Certainty
index
I002166
001
4/
28/
95
NC
Trout
(100s)
Yes+
0.43
10.74
ppm
in
tissue
0.12
1.6
ppm
in
soil
Tree
farm
Highly
Probable
(Accident)
B0000
204
5/
1/
83
SC
Mullet
(100)
No
N/
A
Ag
area
Possible
I004632
033
4/
29/
93
CA
Trout
(60)
No
N/
A
N/
R
Probable
B0000
244
01
8/
7/
71
MA
Fish
(15,000)
No
N/
A
Cranberries
Probable
+=
positive
Exposure
and
Risk
to
Nontarget
Terrestrial
Organisms
Birds:
Acute
Granular
products/
Seed
Treatment:
Birds
may
be
exposed
to
granular
pesticides
and
seed
treatments
by
ingesting
granules
or
seeds
when
foraging
for
food
or
grit.
They
also
may
be
exposed
by
other
routes,
such
as
by
walking
on
exposed
granules
or
drinking
water
contaminated
by
granules
or
treated
seeds.
The
assessment
below
bases
acute
exposure
on
the
quantity
of
seeds
that
a
bird
could
ingest
in
one
day
and
that
the
bird
eats
only
lindanetreated
seeds.
This
approach
defines
a
risk
quotient
(RQ)
as
RQ=
Dose/
LD50
where
Dose
=
the
amount
of
lindane
that
a
bird
could
receive
by
ingesting
treated
seeds
in
a
24
hour
period
per
bird
mass
(dose
units
in
mg/
Kg).
Risk
is
assumed
to
occur
for
any
RQ
value
greater
than0.5.
The
dose
that
a
bird
could
receive
by
eating
treated
seeds
can
be
approximated
from
the
estimated
amount
of
food
that
a
bird
can
eat
in
a
day.
The
dose
can
be
described
as
Dose
=
(FI)(
C)(
T)/
Mbird
where
FI
=
the
food
ingestion
rate
[kg/
day]
C
=
active
ingredient
concentration
on
seed
(mg/
kg)
T
=
relevant
duration
time
for
food
consumption
(assumed
to
be
1
day
in
this
assessment)
[day].
Mbird
=
mass
(wet)
of
bird
[kg].
The
rate
of
food
consumption
(FI)
of
a
bird
can
be
estimated
by
the
method
of
Nagy
(1987;
also
see
EPA,
1993).
For
passerines,
the
Nagy
relationship
is
FI
=
0.
141
(Mbird)
0.850
and
for
non
passerines
the
relationship
is
FI
=
0.
054
(Mbird)
0.751
36
RQ
results
for
this
analysis
are
summarized
in
the
table
below.
The
results
suggest
that
acute
risk
is
highest
for
for
birds
eating
seeds
for
broccoli,
brussel
sprouts,
cabbage,
and
cauliflower.
Small
birds,
which
consume
proportionally
larger
quantities
of
food
with
respect
to
their
body
weight,
are
at
greater
risk
than
larger
birds.
RQs
exceeded
0.5
for
the
sparrow
and
the
red
winged
black
bird
under
for
all
seed
treatments.
For
the
quail,
RQ
indicated
risk
only
for
the
seeds
with
the
highest
application
rate
(broccoli,
brussel
sprouts,
cabbage,
and
cauliflower).
Table
Summary
of
RQ
evaluation.
RQs
in
bold
indicate
potential
risk..
Lindane
Seed
Conc
(per
label)
Dose
(mg
ai
consumed
per
day
/kg
bird)
RQ
=Dose/
LD50
crop
example
label
#
lb
ai/
100
lb
seed
mg
ai/
kg
seed
sparrow
(FI
=
0.00613
kg/
day)
a
RWBB
(FI
=
0.0114
kg/
day)
a
quail
(FI
=
0.0148
kg/
day)
a
sparrow
(LD50=56
mg/
kg)
RWBB
(LD50=75
mg/
kg)
quail
(LD50=122
mg/
kg)
barley
34704
658
0.0375
375
92.0
82.4
31.1
1.64
1.10
0.25
corn
71096
2
0.
125
1250
307
275.
103.
5.48
3.67
0.85
oats
2935
0492
0.0313
313
76.6
68.7
25.9
1.37
0.92
0.21
rye
2935
0492
0.0328
328
80.4
72.1
27.2
1.44
0.96
0.22
sorghum
8660
53
0.0628
628
154.
138.
52.1
2.75
1.84
0.43
wheat
555
144
0.0426
426
104.
93.5
35.3
1.87
1.25
0.29
a
Dose
=
seed
concentration
x
food
intake
rate,
where
food
intake
rate
(FI)
is
based
on
Nagy
equation
(see
text),
assuming
the
following
typical
bird
weights:
Sparrow
wt
=
25
g;
Red
winged
BB
wt
=
52
g,
Bobwhite
quail
wt
=
178
g
(Clench
and
Leberman.
1978).
Birds:
Chronic
To
determine
chronic
risk
to
birds,
the
concentration
on
the
food
item
(seeds)
was
determined
from
the
the
label.
Chronic
RQ
was
calculated
using
the
following
equation:
RQ
=
Concentration
on
seeds
/
NOAEC.
Results
are
given
in
the
table
below
and
suggest
a
potential
for
chronic
reproductive
risk
to
avian
species
from
the
use
of
lindane
treated
seed.
Table
summary
of
chronic
RQ
evaluation.
RQs
in
bold
indicate
potential
risk..
Lindane
Seed
Conc
(per
label)
RQ
=Seed
Conc./
NOAEC
crop
example
label
#
lb
ai/
100
lb
seed
mg
ai/
kg
seed
mallard
(NOAEC=
15
mg/
kg)
Quail
(NOAEC
=
80
mg/
kg)
barley
34704
658
0.0375
375
25
4.7
corn
71096
2
0.
125
1250
83.3
15.6
oats
2935
0492
0.0313
313
20.8
3.
9
rye
2935
0492
0.0328
328
21.9
4.
1
sorghum
8660
53
0.0628
628
41.9
7.
9
wheat
555
144
0.0426
426
28.4
5.
3
Mammals:
Acute
Granular
products/
Seed
Treatment:
Mammals
may
be
exposed
to
granular
pesticides
ingesting
granules
or
seeds
when
foraging
for
food
or
grit.
They
also
may
be
exposed
by
other
routes,
such
as
by
walking
on
exposed
granules
or
drinking
water
contaminated
by
granules
or
treated
seeds.
The
assessment
was
performed
in
a
similar
manner
as
for
birds
as
given
above.
The
Nagy
relationship
for
the
general
case
of
all
mammals
is
FI
=
0.
0687
(Mmammals)
0.822
where
Mmammals
is
the
mammal
mass
in
kg.
Results
are
summarized
below.
Since
RQs
above
0.
5
indicate
potential
risk,
the
results
indicate
the
possibility
of
acute
risk
to
seed
eating
mammals
for
all
seed
treatments,
with
smaller
mammals
being
more
vulnerable
than
larger
mammals..
37
Table
summary
of
RQ
evaluation.
RQs
in
bold
indicate
potential
risk..
Lindane
Seed
Conc
(per
label)
Dose
(mg
ai
consumed
per
day
/kg
mammal)
RQ
=Dose/
LD50
crop
example
label
#
lb
ai/
100
lb
seed
mg
ai/
kg
seed
0.015
kg
mammal
(FI
=
0.00218
kg/
day)
a
0.035
kg
mammal
(FI
=
0.00437
kg/
day)
a
1
kg
mammal
(FI
=
0.0687
kg/
day)
a
0.015
kg
mammal
LD50=88
mg/
kg)
b
0.035
kg
mammal
(LD50=88
mg/
kg)
b
1
kg
mammal
(LD50=88
mg/
kg)
b
barley
34704
658
0.0375
375
54
47
26
0.62
0.53
0.29
corn
71096
2
0.
125
1250
181
156
86
2.1
1.
8
0.98
oats
2935
0492
0.0313
313
45
39
21
0.51
0.44
0..
24
rye
2935
0492
0.0328
328
47
41
23
0.54
0.46
0.26
sorghum
8660
53
0.0628
628
91
78
43
1.0
0.
89
0.49
wheat
555
144
0.0426
426
62
53
29
0.70
0.60
0.33
a
Dose
=
seed
concentration
x
food
intake
rate,
where
food
intake
rate
(FI)
is
based
on
Nagy
equation
(see
text).
Weights
were
chosen
to
represent
typical
small
mammals.
b
AllLD50s
were
based
on
the
rat.
Mammals:
Chronic
To
determine
chronic
risk
to
mammals,
the
concentration
on
the
food
item
(seeds)
was
determined
from
the
the
label.
Chronic
RQ
was
calculated
using
the
following
equation:
RQ
=
Concentration
on
seeds
/
NOAEC.
The
NOAEC
for
the
rat
(20
mg/
L)
was
used
as
an
approximation
for
all
mammals.
Results
are
given
in
the
table
below
and
indicate
a
potential
for
chronic
reproductive
risk
to
mammalian
species
from
the
use
of
lindane
treated
seed.
Table
summary
of
chronic
RQ
evaluation.
RQs
in
bold
indicate
potential
risk..
Lindane
Seed
Conc
(per
label)
RQ
=Seed
Conc./
NOAEC
crop
example
label
#
lb
ai/
100
lb
seed
mg
ai/
kg
seed
rat
(NOAEC=
20
mg/
kg)
barley
34704
658
0.0375
375
19
corn
71096
2
0.
125
1250
63
oats
2935
0492
0.0313
313
16
rye
2935
0492
0.0328
328
16
sorghum
8660
53
0.0628
628
31
wheat
555
144
0.0426
426
21
Insects
Currently,
EFED
does
not
assess
risk
to
nontarget
insects.
Results
of
acceptable
studies
are
used
for
recommending
appropriate
label
precautions.
As
lindane
is
highly
toxic
(0.2
to
0.
56
ug/
bee)
to
honeybees,
precautions
in
respect
to
spray
drift
to
flowering
plants
should
be
followed.
Since
this
is
a
seed
treatment
application,
low
risk
is
assumed
to
flying
insects,
however
beneficial
soil
dwelling
insects
may
be
at
risk.
Plants
No
data
was
available
for
lindane
to
assess
risk
to
terrestrial
or
aquatic
plants.
Exposure
and
Risk
to
Nontarget
Freshwater
Aquatic
Animals
38
EFED
uses
GENEEC
to
calculate
Tier
I
EECs
and
assumed
that
100%
of
the
compound
will
disassociate
from
the
seed
surface.
EECs
are
tabulated
in
Appendix
III.
I.
Freshwater
Fish
Acute
and
chronic
risk
quotients
are
tabulated
below.
Risk
Quotients
for
Freshwater
Fish
Based
On
a
bluegill
LC50
of
1.7
ppb
and
a
fathead
minnow
NOAEC
of
2.9
ppb.
Site
LC50
(ppb)
NOAEC
(ppb)
EEC
Initial/
Peak
(ppb)
EEC
56
Day
Ave.
(ppb)
Acute
RQ
(EEC/
LC50)
Chronic
RQ
(EEC/
NOAEC)
wheat
1.
7
2.
9
0.
67
0.
48
0.
40
0.
17
An
analysis
of
the
results
indicate
that
restricted
use
and
endangered
species
LOC's
are
exceeded
for
freshwater
fish.
No
chronic
LOC's
are
exceeded
for
freshwater
fish.
ii.
Freshwater
Invertebrates
The
acute
and
chronic
risk
quotients
are
tabulated
below.
Risk
Quotients
for
Freshwater
Invertebrates
Based
On
a
daphnia
EC50/
LC50
of
10.0
ppb
and
a
daphnia
NOAEC
of
54
ppb.
Site
LC50
(ppb)
21
day
NOAEC
(ppb)
EEC
Initial/
Peak
(ppb)
EEC
21
Day
Average
Acute
RQ
(EEC/
LC50)
Chronic
RQ
(EEC/
NOAEC)
wheat
10
54
0.
67
0.
48
0.07
0.01
An
analysis
of
the
results
indicate
that
the
acute
endangered
species
LOC
is
exceeded
for
freshwater
invertebrates.
No
chronic
LOC's
are
exceeded
for
freshwater
invertebrates.
iii.
Estuarine
and
Marine
Fish
The
acute
and
chronic
risk
quotients
are
tabulated
below.
Risk
Quotients
for
estuarine/
marine
fish
based
on
a
striped
mullet
LC50
of
23
ppb.
No
data
was
submitted
to
assess
chronic
risk
to
estuarine/
marine
fish.
Site
LC50
(ppb)
NOAEC
(ppb)
EEC
Initial/
Peak
(ppb)
EEC
56
Day
Average
Acute
RQ
(EEC/
LC50)
Chronic
RQ
(EEC/
NOAEC)
wheat
23
N/
A
0.67
0.48
0.03
N/
A
An
analysis
of
the
results
indicate
that
no
acute
LOCs
were
exceeded
for
estuarine/
marine
fish.
iv.
Estuarine
and
Marine
Invertebrates
39
Risk
Quotients
for
Estuarine/
Marine
Aquatic
Invertebrates
Based
on
a
pink
shrimp
LC50/
EC50
of
0.077
ppb.
No
data
was
submitted
to
assess
chronic
risk
to
estuarine/
marine
invertebrates.
Site/
Application
Method
LC50
(ppb)
NOAEC/
(ppb)
EEC
Initial/
Peak
EEC
21
Day
Average
Acute
RQ
(EEC/
LC50)
Chronic
RQ
(EEC/
NOAEC)
wheat
0.
077
N/
A
0.
67
0.
48
8.
70
N/
A
An
analysis
of
the
results
indicate
that
high
acute,
restricted
use
and
endangered
species
LOC's
were
exceeded
for
estuarine/
marine
invertebrates.
Chronic
risk
to
estuarine/
marine
invertebrates
could
not
be
assessed
due
to
a
lack
of
toxicity
data.
40
Appendix
III:
GENEEC
OUTPUT
(FOR
SURFACE
WATER
ASSESSMENT)
RUN
No.
1
FOR
lindane
INPUT
VALUES
RATE
(#/
AC)
APPLICATIONS
SOIL
SOLUBILITY
%
SPRAY
INCORP
ONE(
MULT)
NO.
INTERVAL
KOC
(PPM)
DRIFT
DEPTH(
IN)
.051(
.051)
1
1
942.0
7.0
.0
1.0
FIELD
AND
STANDARD
POND
HALFLIFE
VALUES
(DAYS)
METABOLIC
DAYS
UNTIL
HYDROLYSIS
PHOTOLYSIS
METABOLIC
COMBINED
(FIELD)
RAIN/
RUNOFF
(POND)
(POND
EFF)
(POND)
(POND)
980.00
2
N/
A
.00
.00
.00
*******
GENERIC
EECs
(IN
PPT)
PEAK
AVERAGE
4
AVERAGE
21
AVERAGE
56
GEEC
DAY
GEEC
DAY
GEEC
DAY
GEEC
671.90
655.43
579.19
483.61
SCIGROW
OUTPUT
(FOR
GROUND
WATER
ASSESSMENT
RUN
No.
1
FOR
lindane
INPUT
VALUES
APPL
(#/
AC)
APPL.
URATE
SOIL
SOIL
AEROBIC
RATE
NO.
(#/
AC/
YR)
KOC
METABOLISM
(DAYS)
.051
1
.051
1367.0
980.0
GROUND
WATER
SCREENING
CONCENTRATIONS
IN
PPB
.010993
A=
975.000
B=
1372.000
C=
2.989
D=
3.137
RILP=
2.578
F=
.
668
G=
.215
URATE=
.051
GWSC=
.010993
41
Ecological
Effects
Data
Requirements
for:
LINDANE
Guideline
#
Data
Requirement
Is
Data
Requirement
Satisfied?
MRID
#'s
Study
Classification
71
1
Avian
Oral
LD50
Yes
00263944
Core
71
2
2
Avian
Dietary
LC50's
Yes
00022923
Core
71
4
Avian
Reproduction
Yes
No
448122
01
448671
01
Core
Supplemental
72
1
2
Freshwater
Fish
LC50
Yes
Yes
400946
02
400980
01
Core
Core
72
2
Freshwater
Invertebrate
Acute
LC50
Yes
400946
02
Core
72
3(
a)
Estuarine/
Marine
Fish
LC50
Yes
in
combination
402284
01
(5
studies)
Supplemental
72
3(
b)
Estuarine/
Marine
Mollusk
EC50
Yes
402284
01
Core
72
3(
c)
Estuarine/
Marine
Shrimp
EC50
Yes
in
combination
402284
01
400946
02
(5
studies)
Supplemental
Supplemental
72
4(
a)
Freshwater
Fish
Early
Life
Stage
Yes
444054
01
400561
05
Supplemental
72
4(
b)
Estuarine
Fish
Early
Life
Stage
Required
72
4(
c)
Estuarine
Invertebrate
Life
Cycle
Required
72
4(
d)
Freshwater
Invertebrate
Life
Cycle
Yes
444054
02
400561
06
Supplemental
72
5
Freshwater
Fish
Full
Life
Cycle
Reserved
81
1
Acute
Mammalian
LD50
Yes
00049330
Core
83
5
2
generation
mammalian
reproduction
Yes
422461
01
Core
122
1(
a)
Seed
Germ./
Seedling
Emergence
Required
122
1(
b)
Vegetative
Vigor
Required
122
2
Aquatic
Plant
Growth
Required
123
1(
a)
Seed
Germ./
Seedling
Emergence
Reserved
123
1(
b)
Vegetative
Vigor
Reserved
123
2
Aquatic
Plant
Growth
Reserved
144
1
Honey
Bee
Acute
Contact
LD50
Yes
Yes
00036935
05001991
Core
Core
Non
guideline
14
day
free
choice
avian
dietary
toxicity
test
(aversion)
Not
required
400561
03;
400561
04
Supplemental
42
Environmental
Fate
Data
Requirements
for:
LINDANE
Guideline
#
Data
Requirement
Is
Data
Requirement
Satisfied?
MRID
#'s
Study
Classification
161
1
Hydrolysis
Yes
00161630
Accepted
161
2
Photodegradation
in
Water
Yes
00164547
00164545
44793101
Supplemental
Supplemental
Acceptable
161
3
Photodegradation
on
Soil
Yes
44440605
Acceptable
161
4
Photodegradation
in
Air
N/
A
N/
A
N/
A
162
1
Aerobic
Soil
Metabolism
Yes
40622501
Accepted
162
2
Anaerobic
Soil
Metabolism
No
44867102
Unacceptable
162
3
Anaerobic
Aquatic
Metabolism
N/
A
N/
A
N/
A
162
4
Aerobic
Aquatic
Metabolism
N/
A
N/
A
N/
A
163
1
Leaching
Adsorption/
Desorption
yes
00164346
00164538
40067301
Accepted
163
2
Laboratory
Volatility
No
44445301
Unacceptable
1
163
3
Field
Volatility
N/
A
N/
A
N/
A
164
1
Terrestrial
Field
Dissipation
Yes
44867103
Supplemental
165
4
Accumulation
in
Fish/
Bioconcentration
Yes
40056101
40056102
Accepted
1.
Sorption
properties
of
lindane
and
the
soil
were
not
reported.
Additional
volatility
study
submissions
are
not
needed
to
assess
this
chemicals
fate,
since
lindane's
volatility
is
well
documented
in
open
literature.
| epa | 2024-06-07T20:31:43.146436 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0202-0012/content.txt"
} |
EPA-HQ-OPP-2002-0202-0013 | Supporting & Related Material | "2002-08-14T04:00:00" | null | UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
WASHINGTON,
D.
C.
20460
PC
Code:
009001
DP
Barcodes:
D283667
MEMORANDUM
SUBJECT:
Addition
of
corn
and
canola
seed
treatment
use
to
revised
Lindane
RED
TO:
B.
Shackleford,
Branch
Chief
M.
Howard,
Team
Leader
Special
Review
and
Reregistration
Division
(7508C)
FROM:
N.
E.
Federoff,
Wildlife
Biologist
F.
A.
Khan,
Ph.
D.,
Environmental
Scientist
Environmental
Risk
Branch
V
Environmental
Fate
and
Effects
Division
REVIEWED
and
APPROVED
by:
Mah
Shamim,
Ph.
D.,
Branch
Chief
Environmental
Risk
Branch
V
Environmental
Fate
and
Effects
Division
(7507C)
CANOLA
AND
CORN
SEED
ASSESSMENT
EFED
was
asked
to
add
canola
and
corn
to
its
list
of
lindane
treated
seeds
for
ecological
risk
assessment.
This
document
supersedes
the
Revised
EFED
RED
chapter
for
lindane
(D254764)
and
provides
updated
and
revised
risk
information
regarding
canola
and
corn.
Both
a
terrestrial
(avian
and
mammalian
acute
and
chronic)
and
an
aquatic
assessment
(freshwater
and
marine
fish
and
invertebrates)
were
performed
as
well
as
calculation
of
surface
and
groundwater
EECs.
The
rates
used
were
the
proposed
maximum
1.
456
lb
ai/
100lbs
seed
x
8
lbs
seed/
acre
=
0.
116
lbs
ai/
acre
for
canola
and
a
new
lower
rate
of
0.0558
lb
ai/
100lbs
seed
x
14
lbs
seed/
acre=
0.0078
lbs
ai/
acre
for
corn.
There
are
approximately
113,000
227,000
seeds
per
pound
of
canola
seed
and
1200
1600
seeds
per
pound
of
corn
seed.
Summary
Risk
to
birds
and
mammals
have
increased
in
magnitude
(over
10X)
for
the
new
proposed
canola
use
and
were
reduced
(about
2X)
for
corn
under
the
new
rate
scenario.
However,
uncertainty
exists
regarding
actual
risk
to
seed
eating
avian
species
due
to
factors
associated
with
exposure.
Seed
incorporation
may
reduce
availability
of
treated
seed
to
some
species
and
aversion
and
field
studies
(Blus
et
al.
1984
and
1985)
suggest
birds
may
not
be
consuming
treated
seed.
These
exposure
factors
are
not
applicable
to
small
seed
eating
mammals
that
eat
a
large
proportion
of
their
bodyweight
in
seed
per
day.
Therefore,
the
potential
for
risk
to
these
mammals
is
not
as
uncertain.
Risks
to
aquatic
organisms
did
increased
from
the
new
higher
rate
for
canola.
However,
the
assumption
for
GENEEC
2
(Tier
I
water
exposure
model)
that
100%
of
the
compound
will
disassociate
from
the
seed
surface
has
likely
produced
highly
conservative
estimates
and
has
thus
may
have
overestimated
risks.
Drinking
Water
Assessment
EFED
recommends
that
the
Health
Effects
Division
(HED)
use
the
groundwater
(acute
and
chronic
=
0.05
ppb)
and
surface
water
concentrations
(acute
=
4.
16
ppb
and
chronic
=
1.
95
ppb)
for
canola
presented
in
the
table
below
for
drinking
water
EECs
ONLY
IF
the
proposed
canola
use
will
be
supported.
IF
canola
will
not
be
supported
for
registration,
then
the
concentrations
for
wheat
should
be
used.
The
drinking
water
EECs
were
based
on
the
Tier
I
FIRST
(surface
water)
and
SCIGROW
(groundwater)
simulation
models.
The
GENEEC
model
is
no
longer
used
to
estimate
EECs
for
drinking
water.
Therefore,
surface
water
EECs
for
wheat
have
been
revised
using
the
Tier
I
FIRST
model.
The
results
are
provided
in
the
following
table:
Drinking
water
EEC
comparison
for
lindane
wheat
and
canola
seed
treatments.
WHEAT
Application
Rate
(lbs
ai/
A)
Acute
Chronic
Groundwater
0.051
0.011
µ
g/
L
0.
011
µ
g/
L
Surface
Water
0.051
0.
98
µ
g/
L
0.
46
µ
g/
L
CANOLA
Application
Rate
(lbs
ai/
A)
Acute
Chronic
Groundwater
0.
116
0.025
µ
g/
L
0.
025
µ
g/
L
Surface
Water
0.116
4.16
µ
g/
L
1.
95
µ
g/
L
Ground
Water
Ground
water
concentrations
were
predicted
with
SCIGROW.
Input
parameters
are
summarized
in
the
table
below.
The
entire
SCIGROW
output
file
is
located
in
Appendix
I
at
the
end
of
this
memo.
SCIGROW
input
parameters
and
results
for
lindane.
Application
Rate:
Wheat
Canola
1
@
0.
051
lb/
acre
1
@
0.
116
lb/
acre
Aerobic
Soil
Half
Life
980
days
(mean
Value)
Organic
Carbon
Partitioning
Coefficient
(Koc)
1367
mL/
g
(median
Value)
EEC:
Wheat
Canola
0.011
µg/
L
0.013
µg/
L
Surface
Water
The
following
inputs
were
used
for
the
FIRST
modeling.
The
FIRST
output
file
is
located
in
Appendix
I
at
the
end
of
this
memo.
Input
Parameters
for
FIRST
Parameter
Value
Application
Rate
and
Number
0.
051
lb
ai/
A
x
1
application
(Wheat)
0.
116
lb
ai/
A
x
1
application
(Canola)
Organic
Carbon
Partitioning
Coefficient
942
ml/
g
lowest
of
4
values
(MRID
00164346)
Solubility
7
ppm
Application
Type
Granular/
incorporated
to
1.
2
inches
Percent
Cropped
Area
56%
for
Wheat
and
87%
for
Canola
Aerobic
Soil
Half
life
980
days
single
value
(MRID
406225
01)*
Aerobic
Aquatic
Half
life
1960
days
(aerobic
soil
halflife
x
2)
Photolysis
stable
(MRIDs
0016457;
001645545;
447931)
Hydrolysis
stable
(MRID
00161630)
*In
a
336
day
aerobic
soil
metabolism
study,
lindane
degraded
very
slowly,
with
a
registrant
calculated
half
life
of
980
days,
thus
the
"3x"
rule
was
not
applied.
Terrestrial
and
Aquatic
Assessments
Risk
to
birds
and
mammals
have
increased
in
magnitude
(over
10X)
for
the
proposed
canola
use.
However,
uncertainty
exists
regarding
actual
risk
to
seed
eating
avian
species
due
to
factors
associated
with
exposure.
Seed
incorporation
may
reduce
availability
of
treated
seed
to
some
species.
Aversion
and
field
studies
(Blus
et
al.
1984
and
1985)
suggest
birds
may
not
be
consuming
treated
seed.
These
exposure
factors
are
not
applicable
to
small
seed
eating
mammals
that
eat
a
large
proportion
of
their
bodyweight
in
seed
per
day.
Therefore,
the
potential
for
risk
to
these
mammals
is
not
as
uncertain.
Risks
to
aquatic
organisms
increased
only
slightly.
The
assumption
for
GENEEC
2
(Tier
I
water
exposure
model)
that
100%
of
the
compound
will
disassociate
from
the
seed
surface
has
likely
produced
highly
conservative
estimates
and
has
thus
likely
overestimated
the
EEC's
and
resulting
risks.
EFED
also
believes
that
a
seed
leaching
study
would
greatly
increase
certainty
regarding
a
more
realistic
estimate
of
compound
for
groundwater
leaching
and
runoff.
This
in
turn
would
allow
a
refinement
of
exposure
estimates
and
environmental
concentration
values
(EECs).
EFED
has
issued
a
guidance
for
this
study
(Memo
from
Denise
Keehner
re:
Standard
Method
for
Determining
the
Leachability
of
Pesticides
from
Treated
Seeds,
7/
6/
2000).
The
results
of
the
risk
assessment
are
as
follows:
Avian
The
labels
with
the
highest
rates
(lb
lindane/
100
lb
seed)
were
used
to
evaluate
potential
maximum
consumption
of
lindane
by
terrestrial
animals.
The
current
approach
uses
daily
food
intake
calculated
using
the
relationships
described
in
Nagy
(1987
as
cited
in
USEPA,
1993).
Acute
risk
quotients
(RQ)
were
then
calculated
based
on
animals
receiving
their
full
diet
from
lindane
treated
seeds
for
a
1
day
time
period.
In
addition,
RQs
were
calculated
using
the
mg
ai/
kg/
seed
and
the
dietary
LC50
endpoint.
Birds
may
be
exposed
to
granular
pesticides
and
seed
treatments
by
ingesting
granules
or
seeds
when
foraging
for
food
or
grit.
They
also
may
be
exposed
by
other
routes,
such
as
by
walking
on
exposed
granules
or
drinking
water
contaminated
by
granules
or
treated
seeds.
The
assessment
below
bases
acute
exposure
on
the
quantity
of
seeds
that
a
bird
could
ingest
in
one
day
and
that
the
bird
eats
only
lindane
treated
seeds.
This
approach
defines
a
risk
quotient
(RQ)
as:
RQ=
Dose/
LD50
where
Dose
=
the
amount
of
lindane
that
a
bird
could
receive
by
ingesting
treated
seeds
in
a
24
hour
period
per
bird
mass
(dose
units
in
mg/
Kg).
Risk
is
assumed
to
occur
for
any
RQ
value
greater
than
0.5.
The
dose
that
a
bird
could
receive
by
eating
treated
seeds
can
be
approximated
from
the
estimated
amount
of
food
that
a
bird
can
eat
in
a
day.
The
dose
can
be
described
as:
Dose
=
(FI)(
C)(
T)/
Mbird
where
FI
=
the
food
ingestion
rate
[kg/
day]
C
=
active
ingredient
concentration
on
seed
(mg/
kg)
T
=
relevant
duration
time
for
food
consumption
(assumed
to
be
1
day
in
this
assessment)
[day].
Mbird
=
mass
(wet)
of
bird
[kg].
The
rate
of
food
consumption
(FI)
of
a
bird
can
be
estimated
by
the
method
of
Nagy
(1987;
also
see
EPA,
1993).
For
passerines,
the
Nagy
relationship
is:
FI
=
0.
141
(Mbird)
0.850
and
for
non
passerines
the
relationship
is:
FI
=
0.
054
(Mbird)
0.751
Acute
RQ
results
for
this
analysis
are
summarized
in
the
table
below.
Small
birds,
which
consume
proportionally
larger
quantities
of
food
with
respect
to
their
body
weight,
are
at
greater
risk
than
larger
birds.
RQs
exceeded
0.5
for
the
sparrow
and
the
red
winged
black
bird
for
all
seed
treatments.
For
the
quail,
RQ
indicated
risk
only
for
the
seeds
with
the
highest
application
rates.
However,
even
when
RQs
were
calculated
using
the
dietary
LC50
for
quail,
risk
was
exceeded
for
all
seed
types.
Thus
it
can
be
implied
that
seed
eating
birds
with
smaller
body
weights
than
the
quail
may
be
at
increased
risk
since
lindane
toxicity
seems
to
be
inversely
related
to
bodyweight.
Table
Summary
of
RQ
evaluation.
RQs
in
bold
indicate
potential
risk..
Lindane
Seed
Conc
(per
label)
Dose
(mg
ai
consumed
per
day
/kg
bird)
RQ
=Dose/
LD50
RQ=
Seed
concentration/
LC50
crop
example
label
#
lb
ai/
100
lb
seed
mg
ai/
kg
seed
sparrow
(FI
=
0.00613
kg/
day)
a
RWBB
(FI
=
0.0114
kg/
day)
a
quail
(FI
=
0.0148
kg/
day)
a
sparrow
(LD50=56
mg/
kg)
RWBB
(LD50=75
mg/
kg)
quail
(LD50=122
mg/
kg)
Quail
LC50=425
ppm
barley
34704
658
0.0375
375
92.0
82.4
31.1
1.64
1.10
0.25
0.88
corn
71096
2
0.
125
1250
307
275
103
5.48
3.67
0.85
2.94
LOW
rate
corn
proposed
0.
0558
558
137
122
46
2.45
1.64
0.38
1.31
oats
2935
0492
0.0313
313
76.6
68.7
25.9
1.37
0.92
0.21
0.74
rye
2935
0492
0.0328
328
80.4
72.1
27.2
1.44
0.96
0.22
0.77
sorghum
8660
53
0.0628
628
154
138
52.1
2.75
1.84
0.43
1.48
wheat
555
144
0.0426
426
104
93.5
35.3
1.86
1.25
0.29
1.00
Canola
(proposed
maximum
rate)
proposed
1.
456
14560
3570
3192
1211
63.75
42.56
9.93
34.26
Canola
½
rate
proposed
0.
72
7200
1765
1578
599
31.51
21.04
4.91
16.94
a
Dose
=
seed
concentration
x
food
intake
rate,
where
food
intake
rate
(FI)
is
based
on
Nagy
equation
(see
text),
assuming
the
following
typical
bird
weights:
Sparrow
wt
=
25
g;
Red
winged
BB
wt
=
52
g,
Bobwhite
quail
wt
=
178
g
(Clench
and
Leberman.
1978).
Chronic
To
determine
chronic
risk
to
birds,
the
concentration
on
the
food
item
(seeds)
was
determined
from
the
label.
Chronic
RQ
was
calculated
using
the
following
equation:
RQ
=
Concentration
on
seeds
/
NOAEC.
Results
are
given
in
the
table
below
and
suggest
a
potential
for
chronic
reproductive
risk
to
avian
species
from
the
use
of
lindane
treated
seed.
RQs
in
bold
indicate
potential
risk.
Lindane
Seed
Conc
(per
label)
RQ
=Seed
Concentration/
NOAEC
crop
example
label
#
lb
ai/
100
lb
seed
mg
ai/
kg
seed
mallard
(NOAEC=
15
mg/
kg)
Quail
(NOAEC
=
80
mg/
kg)
barley
34704
658
0.0375
375
25.0
4.7
corn
71096
2
0.
125
1250
83.3
15.6
LOW
rate
corn
proposed
0.
0558
558
37.2
6.9
oats
2935
0492
0.0313
313
20.8
3.9
rye
2935
0492
0.0328
328
21.9
4.1
sorghum
8660
53
0.0628
628
41.9
7.9
wheat
555
144
0.0426
426
28.4
5.3
Canola
(proposed
maximum
rate)
proposed
1.
456
14560
970.7
182.0
Canola
½
rate
proposed
0.
72
7200
480.0
90.0
Mammalian
Mammals
may
be
exposed
to
granular
pesticides
ingesting
granules
or
seeds
when
foraging
for
food
or
grit.
They
also
may
be
exposed
by
other
routes,
such
as
by
walking
on
exposed
granules
or
drinking
water
contaminated
by
granules
or
treated
seeds.
The
mammalian
assessment
was
performed
in
a
similar
manner
as
for
birds
as
given
above.
In
addition,
RQs
were
calculated
using
the
mg
ai/
kg/
seed
and
the
dietary
LC50
endpoint.
The
Nagy
relationship
for
the
general
case
of
all
mammals
is:
FI
=
0.
0687
(Mmammals)
0.822
where
Mmammals
is
the
mammal
mass
in
kg.
Results
are
summarized
below.
Since
RQs
above
0.
5
indicate
potential
risk,
the
results
indicate
the
possibility
of
acute
risk
to
seed
eating
mammals
for
all
seed
treatments,
including
canola,
with
smaller
mammals
being
more
vulnerable
than
larger
mammals.
Table
summary
of
RQ
evaluation.
RQs
in
bold
indicate
potential
risk..
Lindane
Seed
Conc
(per
label)
Dose
(mg
ai
consumed
per
day
/kg
mammal)
RQ
=Dose/
LD50
RQ=
Seed
concentration/
LC5
Calculated
dietary
effect
concentration
crop
example
label
#
lb
ai/
100
lb
seed
mg
ai/
kg
seed
0.015
kg
mammal
(FI
=
0.00218
kg/
day)
a
0.035
kg
mammal
(FI
=
0.00437
kg/
day)
a
1
kg
mammal
(FI
=
0.0687
kg/
day)
a
0.015
kg
mammal
LD50=88
mg/
kg)
0.035
kg
mammal
(LD50=88
mg/
kg)
1
kg
mammal
(LD50=88
mg/
kg)
419
ppm
587
ppm
1760
ppm
barley
34704
658
0.0375
375
54
47
26
0.62
0.53
0.29
0.90
0.64
0.21
corn
71096
2
0.
125
1250
181
156
86
2.1
1.
8
0.98
3.00
2.13
0.71
LOW
rate
corn
proposed
0.
0558
558
81
70
38
0.92
0.79
0.44
1.33
0.95
0.32
oats
2935
0492
0.0313
313
45
39
21
0.51
0.44
0.24
0.75
0.53
0.18
radish
7501
16
0.0323
323
47
40
22
0.53
0.45
0.25
0.77
0.55
0.18
rye
2935
0492
0.0328
328
47
41
23
0.54
0.46
0.26
0.78
0.56
0.19
sorghum
8660
53
0.0628
628
91
78
43
1.0
0.
89
0.49
1.50
1.07
0.36
wheat
555
144
0.0426
426
62
53
29
0.70
0.60
0.33
1.02
0.73
0.24
Canola
(proposed
maximum
rate)
proposed
1.
456
14560
2116
1818
1000
24
21
11
34.75
24.80
8.27
Canola
½
rate
proposed
0.
72
7200
1046
899
495
12
10
6
17.18
12.27
4.09
a
Dose
=
seed
concentration
x
food
intake
rate,
where
food
intake
rate
(FI)
is
based
on
Nagy
equation
(see
text).
Weights
were
chosen
to
represent
typical
small
mammals.
All
calculated
LD50s
andLC50s
were
based
on
the
LD50
(88
mg/
kg)
data
for
the
rat.
RQ
=
EEC
(mg/
kg)
LD50
(mg/
kg)/
%
Body
Weight
Consumed
where
the
%
body
weight
consumed
varies
with
body
size:
Granivores:
21%
for
15
g
wt;
15%
for
35
g
wt;
5%
for
1000
g
wt.
Chronic
To
determine
chronic
risk
to
mammals,
the
concentration
on
the
food
item
(seeds)
was
determined
from
the
the
label.
Chronic
RQ
was
calculated
using
the
following
equation:
RQ
=
Concentration
on
seeds
/
NOAEC.
The
NOAEC
for
the
rat
(20
mg/
kg)
was
used
as
an
approximation
for
all
mammals.
Results
are
given
in
the
table
below
and
indicate
a
potential
for
chronic
reproductive
risk
to
mammalian
species
from
the
use
of
lindane
treated
seed.
Table
summary
of
chronic
RQ
evaluation.
RQs
in
bold
indicate
potential
risk..
Lindane
Seed
Conc
(per
label)
RQ
=Seed
Concentration/
NOAEC
crop
example
label
#
lb
ai/
100
lb
seed
mg
ai/
kg
seed
rat
(NOAEC=
20
mg/
kg)
barley
34704
658
0.0375
375
19
corn
71096
2
0.
125
1250
63
LOW
rate
corn
proposed
0.
0558
558
28
oats
2935
0492
0.0313
313
16
radish
7501
16
0.0323
323
16
rye
2935
0492
0.0328
328
16
sorghum
8660
53
0.0628
628
31
wheat
555
144
0.0426
426
21
Canola
(proposed
maximum
rate)
proposed
1.
456
14560
728
Canola
½
rate
proposed
0.
72
7200
360
Aquatic
Assessment
EFED
uses
GENEEC
2
to
calculate
Tier
I
aquatic
EECs
and
assumed
that
100%
of
the
compound
will
disassociate
from
the
seed
surface.
A
1.
2
inch
incorporation
depth
was
used
for
wheat
and
1
inch
for
canola.
Input
parameters
and
the
resulting
EECs
for
wheat
and
canola
are
tabulated
below:
GENEEC
2
input
parameters
and
results
for
wheat
and
canola.
Application
Rate:
wheat
canola
1
x
0.
051
lb
ai/
A
1
x
0.
116
lb
ai/
A
Aerobic
Soil
Half
Life
980
days
(single
value)
Aerobic
Aquatic
Half
Life
1960
days
(aerobic
soil
T1/
2
x
2)
Incorporation
depth
1.2
inches
for
wheat
and
1
inch
for
canola
Hydrolysis
stable
Photolysis
stable
Spray
Drift
incorporated
seed
treatment
=
0
Organic
Carbon
Partitioning
Coefficient
(Koc)
942
mL/
g
(lowest
value)
Solubility
7
mg/
L
Expected
EEC's
Wheat
Canola
Peak
1.09
µg/
L
2.57
µg/
L
4
day
average
1.08
µg/
L
2.56
µg/
L
21
day
average
1.06
µg/
L
2.49
µg/
L
60
day
average
1.00
µg/
L
2.36
µg/
L
I.
Freshwater
Fish
Acute
and
chronic
risk
quotients
are
tabulated
below.
Risk
Quotients
for
Freshwater
Fish
Based
On
a
brown
trout
LC50
of
1.7
ppb
and
a
rainbow
trout
NOAEC
of
2.9
ppb.
Site
LC50
(ppb)
NOAEC
(ppb)
EEC
Initial/
Peak
(ppb)
EEC
56
or
60
Day
Ave.
(ppb)
Acute
RQ
(EEC/
LC50)
Chronic
RQ
(EEC/
NOAEC)
wheat
0.
05
1.
7
2.
9
0.
94
0.
86
0.55
0.30
Canola
0.116
1.7
2.
9
2.57
2.36
1.51
0.81
An
analysis
of
the
results
indicate
that
acute,
restricted
use
and
endangered
species
LOC's
are
exceeded
for
freshwater
fish.
No
chronic
LOC's
are
exceeded
for
freshwater
fish.
II.
Freshwater
Invertebrates
The
acute
and
chronic
risk
quotients
are
tabulated
below.
Risk
Quotients
for
Freshwater
Invertebrates
Based
On
a
stonefly
EC50/
LC50
of
1.0
ppb
and
a
daphnia
NOAEC
of
54
ppb.
Site
LC50
(ppb)
21
day
NOAEC
(ppb)
EEC
Initial/
Peak
(ppb)
EEC
21
Day
Average
Acute
RQ
(EEC/
LC50)
Chronic
RQ
(EEC/
NOAEC)
Wheat
0.
05
1.
0
54
0.94
0.91
0.94
0.02
Canola
0.116
1.0
54
2.
57
2.
49
2.57
0.05
An
analysis
of
the
results
indicate
that
the
acute,
restricted
use
and
endangered
species
LOCs
are
exceeded
for
freshwater
invertebrates
at
maximum
use
rates.
No
chronic
LOC's
are
exceeded
for
freshwater
invertebrates.
III.
Estuarine
and
Marine
Fish
The
acute
and
chronic
risk
quotients
are
tabulated
below.
Risk
Quotients
for
estuarine/
marine
fish
based
on
a
striped
mullet
LC50
of
23
ppb.
No
data
was
submitted
to
assess
chronic
risk
to
estuarine/
marine
fish.
Site
LC50
(ppb)
NOAEC
(ppb)
EEC
Initial/
Peak
(ppb)
EEC
56
Day
Average
Acute
RQ
(EEC/
LC50)
Chronic
RQ
(EEC/
NOAEC)
Wheat
0.
05
23
N/
A
0.94
0.86
0.04
N/
A
Canola
0.116
23
N/
A
2.
57
2.
36
0.
11
N/
A
An
analysis
of
the
results
indicate
that
acute
restricted
and
endangered
species
LOCs
were
exceeded
for
canola
for
estuarine/
marine
fish.
IV.
Estuarine
and
Marine
Invertebrates
Risk
Quotients
for
Estuarine/
Marine
Aquatic
Invertebrates
Based
on
a
pink
shrimp
LC50/
EC50
of
0.
077
ppb.
No
data
was
submitted
to
assess
chronic
risk
to
estuarine/
marine
invertebrates.
Site/
Application
LC50
(ppb)
NOAEC/
(ppb)
EEC
Initial/
EEC
21
Day
Acute
RQ
(EEC/
LC50)
Chronic
RQ
(EEC/
NOAEC)
Wheat
0.
05
0.
077
N/
A
0.
94
0.
91
12.20
N/
A
Canola
0.116
0.077
N/
A
2.
57
2.
49
33.40
N/
A
An
analysis
of
the
results
indicate
that
acute,
restricted
use
and
endangered
species
LOC's
were
exceeded
for
estuarine/
marine
invertebrates.
Chronic
risk
to
estuarine/
marine
invertebrates
could
not
be
assessed
due
to
a
lack
of
toxicity
data.
APPENDIX
I:
Water
Resource
Model
Results
GENEEC
2
for
Canola
RUN
No.
1
FOR
Lindane
ON
Canola
*
INPUT
VALUES
*
RATE
(#/
AC)
No.
APPS
&
SOIL
SOLUBIL
APPL
TYPE
NO
SPRAY
INCORP
ONE(
MULT)
INTERVAL
Koc
(PPM
)
(%
DRIFT)
(FT)
(IN)
.116(
.116)
1
1
942.0
7.0
GRANUL(
.0)
.0
1.2
FIELD
AND
STANDARD
POND
HALFLIFE
VALUES
(DAYS)
METABOLIC
DAYS
UNTIL
HYDROLYSIS
PHOTOLYSIS
METABOLIC
COMBINED
(FIELD)
RAIN/
RUNOFF
(POND)
(POND
EFF)
(POND)
(POND)
980.00
2
N/
A
.00
.00
******
1960.00
GENERIC
EECs
(IN
MICROGRAMS/
LITER
(PPB))
Version
2.0
Aug
1,
2001
PEAK
MAX
4
DAY
MAX
21
DAY
MAX
60
DAY
MAX
90
DAY
GEEC
AVG
GEEC
AVG
GEEC
AVG
GEEC
AVG
GEEC
2.57
2.56
2.49
2.36
GENEEC
2
for
Wheat
RUN
No.
3
FOR
Lindane
ON
Wheat
*
INPUT
VALUES
*
RATE
(#/
AC)
No.
APPS
&
SOIL
SOLUBIL
APPL
TYPE
NO
SPRAY
INCORP
ONE(
MULT)
INTERVAL
Koc
(PPM
)
(%
DRIFT)
(FT)
(IN)
.051(
.051)
1
1
942.0
7.0
GRANUL(
.0)
.0
1.2
FIELD
AND
STANDARD
POND
HALFLIFE
VALUES
(DAYS)
METABOLIC
DAYS
UNTIL
HYDROLYSIS
PHOTOLYSIS
METABOLIC
COMBINED
(FIELD)
RAIN/
RUNOFF
(POND)
(POND
EFF)
(POND)
(POND)
980.00
2
N/
A
.00
.00
******
1960.00
GENERIC
EECs
(IN
NANOGRAMS/
LITER
(PPB)
Version
2.0
Aug
1,
2001
PEAK
MAX
4
DAY
MAX
21
DAY
MAX
60
DAY
MAX
90
DAY
GEEC
AVG
GEEC
AVG
GEEC
AVG
GEEC
AVG
GEEC
0.941
0.937
0.914
0.864
0.829
SCI
GROW
for
Canola
(Ground
Water
Assessment)
RUN
No.
1
FOR
Lindane
INPUT
VALUES
APPL
(#/
AC)
APPL.
URATE
SOIL
SOIL
AEROBIC
RATE
NO.
(#/
AC/
YR)
KOC
METABOLISM
(DAYS)
0.116
1
0.116
1367.0
980.0
GROUND
WATER
SCREENING
CONCENTRATIONS
IN
PPB
.024907
A=
975.000
B=
1372.000
C=
2.989
D=
3.137
RILP=
2.578
F=
.
668
G=
.215
URATE=
.116
GWSC=
.024907
First
Output
(Surface
Water
Assessment)
for
Wheat
RUN
No.
1
FOR
Lindane
ON
Wheat
*
INPUT
VALUES
*
RATE
(#/
AC)
No.
APPS
&
SOIL
SOLUBIL
APPL
TYPE
%CROPPED
INCORP
ONE(
MULT)
INTERVAL
Koc
(PPM
)
(%
DRIFT)
AREA
(IN)
.051(
0.051)
1
1
942.0
7.0
GRANUL(
.0)
56.0
1.2
FIELD
AND
RESERVOIR
HALFLIFE
VALUES
(DAYS)
METABOLIC
DAYS
UNTIL
HYDROLYSIS
PHOTOLYSIS
METABOLIC
COMBINED
(FIELD)
RAIN/
RUNOFF
(RESERVOIR)
(RES.
EFF)
(RESER.)
(RESER.)
980.00
2
N/
A
.00
.00
******
1960.00
UNTREATED
WATER
CONC
(MICROGRAMS/
LITER
(PPB))
Ver
1.0
AUG
1,
2001
PEAK
DAY
(ACUTE)
ANNUAL
AVERAGE
(CHRONIC)
CONCENTRATION
CONCENTRATION
0.98
0.46
First
Output
for
Canola
(Surface
Water
Assessment)
RUN
No.
1
FOR
Lindane
ON
Canola
*
INPUT
VALUES
*
RATE
(#/
AC)
No.
APPS
&
SOIL
SOLUBIL
APPL
TYPE
%CROPPED
INCORP
ONE(
MULT)
INTERVAL
Koc
(PPM
)
(%
DRIFT)
AREA
(IN)
.116(
0.116)
1
1
942.0
7.0
GRANUL(
.0)
87.0
1.0
FIELD
AND
RESERVOIR
HALFLIFE
VALUES
(DAYS)
METABOLIC
DAYS
UNTIL
HYDROLYSIS
PHOTOLYSIS
METABOLIC
COMBINED
(FIELD)
RAIN/
RUNOFF
(RESERVOIR)
(RES.
EFF)
(RESER.)
(RESER.)
980.00
2
N/
A
.00
.00
******
1960.00
UNTREATED
WATER
CONC
(MICROGRAMS/
LITER
(PPB))
Ver
1.0
AUG
1,
2001
PEAK
DAY
(ACUTE)
ANNUAL
AVERAGE
(CHRONIC)
CONCENTRATION
CONCENTRATION
4.16
1.95
| epa | 2024-06-07T20:31:43.165187 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0202-0013/content.txt"
} |
EPA-HQ-OPP-2002-0202-0014 | Supporting & Related Material | "2002-08-14T04:00:00" | null | PC
Code:
009001
DP
Code:
D283648
MEMORANDUM
DATE:
June
17,
2002
SUBJECT:
Qualitative
Assessment
of
Long
range
Transport
and
Atmospheric
Deposition
of
Lindane
to
Great
Lakes
TO:
Betty
Shackleford,
Branch
Chief
M.
Howard,
Team
Leader
Reregistration
Branch
III
Special
Review
and
Reregistration
Division
(7508C)
FROM:
Faruque
A.
Khan,
Ph.
D.,
Environmental
Scientist
Environmental
Fate
and
Effects
Division
(7507C)
THROUGH:
Mah
T.
Shamim,
Ph.
D.,
Chief
Environmental
Risk
Branch
V
Environmental
Fate
and
Effects
Division
(7507C)
This
memo
presents
the
qualitative
assessment
of
long
range
transport
and
atmospheric
deposition
of
lindane
to
the
Great
Lakes.
The
following
qualitative
assessment
is
based
on
current
literature
available
at
the
present
time.
ASSESSMENT:
LINDANE
IN
THE
GREAT
LAKES
The
ubiquitous
presence
of
lindane
in
atmosphere,
natural
water
bodies,
soils,
and
sediments
of
the
Great
Lakes
regions
implies
redeposition
of
lindane
from
secondary
emissions
and
long
range
transport
of
lindane
from
agricultural
and
industrial
sites.
There
is
very
limited
information
available
to
link
lindane
loading
from
global,
regional,
or
local
sources
to
Great
Lakes.
Strachan
(1985)
estimated
290
kg/
yr
of
lindane
and
860
kg/
yr
of
HCH
loading
from
precipitation
to
Lake
Superior.
Since
1983,
Environment
Canada
is
measuring
the
deposit
of
toxic
contaminants
from
the
atmosphere
to
the
Canadian
side
of
the
Great
Lakes
basin.
Williams
et
al.
(1998)
reported
that
the
deposition
of
lindane
from
precipitation
has
not
changed
since
1990.
They
also
observed
a
seasonal
pattern
of
increased
lindane
concentrations
during
spring
and
summer,
which
suggests
that
agricultural
activities
during
that
time
may
have
been
causing
2
temporal
increases
of
lindane
concentration.
Reported
concentrations
of
water
samples
from
the
channels
of
Great
Lakes
are
very
similar
throughout
the
Great
Lakes
suggest
that
the
atmosphere
is
the
predominant
source
of
lindane.
Elevated
concentrations
in
Lake
Erie
suggest
that
regional
source
may
have
been
contributing
as
well.
There
are
increasing
national
and
international
efforts
to
assess
the
atmospheric
transport
and
deposition
of
toxic
substances
to
the
Great
Lakes.
The
Integrated
Atmospheric
Deposition
Network
(IADN)
was
established
in
1990
by
the
United
States
and
Canada
for
conducting
air
and
precipitation
monitoring
in
the
Great
Lakes
Basin
to
determine
the
magnitude
and
trends
of
atmospheric
loadings
of
toxic
contaminants.
IADN
maintains
monitoring
stations
on
each
of
the
Great
Lakes
to
monitor
atmospheric
deposition
of
selected
pollutants.
IADN
incorporates
wet
deposition,
dry
deposition,
and
net
gas
exchange
atmospheric
deposition
processes
into
its
loading
estimates.
The
temporal
regional
flows
for
both
HCH
and
lindane
(
HCH)
are
presented
in
Figure
1,
which
shows
that
HCH
significantly
decreased
across
the
Great
Lakes
basin
and
has
a
net
volatilization
for
the
first
time
in
1998.
In
contrast,
the
flows
for
lindane
remain
relatively
stable
since
their
decrease
in
1995
due
to
restricted
use
of
lindane
and
the
ban
of
HCH,
which
also
contain
10
18%
of
HCH
isomer
(USEPA,
1998).
Figure
1.
Total
flows
of
HCH
and
HCH
over
all
Great
Lakes
(Sources:
www.
epa.
gov/
glnpo/
iadn/
resources
1998)
Considerable
progress
has
been
made
in
monitoring
and
assessing
the
loading
of
lindane
and
many
other
toxic
contaminants
for
the
Great
Lakes
regions.
The
importance
of
long
range
transport
and
atmospheric
deposition
of
toxic
contaminants
into
the
Great
Lakes
and
their
effects
on
the
chronic
exposer
of
human,
terrestrial,
and
aquatic
organisms
are
only
the
beginning
to
be
understood.
Therefore,
continuing
long
term
monitoring
programs
and
the
evaluation
of
pertinent
3
data
will
help
the
scientists
and
regulatory
authorities
to
develop
preventive
measures
in
reducing
or
eliminating
the
toxic
contaminants
to
Great
Lakes.
References:
Strachan,
W.
M.
J.
1985.
Organic
substances
in
the
rainfall
of
Lake
Superior:
1983.
J.
Environ.
Toxicol.
Chem.
4:
677
683.
U.
S.
EPA,
1998.
Atmospheric
deposion
of
toxic
substances
to
the
Great
Lakes:
IADN
Results
through
1998.
Environment
Canada
and
the
United
States
Environmental
Protection
Agency
www.
epa.
gov/
glnpo/
iadn/).
Williams,
D.
J.,
K.
W.
Kuntz,
S.
L'ltalien,
and
V.
Recardson.
1998.
Lake
Ontario
surveillance
program:
spatial
and
temporal
trends
of
selected
parameters
with
emphasis
on
1992
93
results.
Environment
Canada,
Ecosystem
Health
Division
Report
98
01/
I.
| epa | 2024-06-07T20:31:43.169161 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0202-0014/content.txt"
} |
EPA-HQ-OPP-2002-0202-0015 | Supporting & Related Material | "2002-08-14T04:00:00" | null | PC
Code:
009001
DP
Code:
D283648
MEMORANDUM
DATE:
July
31,
2002
SUBJECT:
Correction
in
Qualitative
Assessment
of
Long
range
Transport
and
Atmospheric
Deposition
of
Lindane
to
Great
Lakes
TO:
Betty
Shackleford,
Branch
Chief
M.
Howard,
Team
Leader
Reregistration
Branch
III
Special
Review
and
Reregistration
Division
(7508C)
FROM:
Faruque
A.
Khan,
Ph.
D.,
Environmental
Scientist
Environmental
Fate
and
Effects
Division
(7507C)
THROUGH:
Mah
T.
Shamim,
Ph.
D.,
Chief
Environmental
Risk
Branch
V
Environmental
Fate
and
Effects
Division
(7507C)
This
memo
presents
a
correction
to
the
memorandum
titled
"Qualitative
Assessment
of
Long
range
Transport
and
Atmospheric
Deposition
of
Lindane
to
the
Great
Lakes"
dated
June
22,
2002.
In
the
1
st
paragraph
of
page
2,
the
last
sentence
"In
contrast,
the
flows
for
lindane
remain
relatively
stable
since
their
decrease
in
1995
due
to
restricted
use
of
lindane
and
the
ban
of
HCH,
which
also
contain
10
18%
of
HCH
isomer
(USEPA,
1998)"
should
read
as
follows:
In
contrast,
the
flows
for
lindane
remain
relatively
stable
since
their
decrease
in
1995
due
to
restricted
use
of
lindane
and
the
ban
of
technical
grade
HCH,
consists
of
mainly
HCH
5570
HCH
(10
18%)
and
trace
amounts
of
and
HCH
isomers
(5
14%)
(USEPA,
1998).
| epa | 2024-06-07T20:31:43.171862 | regulations | {
"license": "Public Domain",
"url": "https://downloads.regulations.gov/EPA-HQ-OPP-2002-0202-0015/content.txt"
} |