Document ID: EPA-HQ-OPP-2005-0478-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2005-12-28T05:00Z

Page
1
of
68
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
Date:
10/
31/
2005
MEMORANDUM
SUBJECT:
Imazaquin
and
its
Salts:
HED
Chapter
of
the
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
Document.
PC
Codes
128840,
128848
&
129023;
DP
Barcode:
D302939
Regulatory
Action:
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
Risk
Assessment
Type:
Single
Chemical
Aggregate
FROM:
Susan
Stanton,
Environmental
Scientist
Reregistration
Branch
3
Health
Effects
Division
(
7509C)

AND
John
Doherty,
Toxicologist
Danette
Drew,
Chemist
Seyed
Tadayon,
Chemist
Reregistration
Branch
3
Health
Effects
Division
(
7509C)

THROUGH:
William
Donovan,
Branch
Senior
Scientist
Reregistration
Branch
3
Health
Effects
Division
(
7509C)

TO:
Craig
Doty,
Chemical
Review
Manager
Special
Review
Branch
SRRD
(
7508C)
Page
2
of
68
Table
of
Contents
1.0
Executive
Summary
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5
2.0
Ingredient
Profile
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9
2.1
Summary
of
Registered
Uses
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10
2.2
Structure
and
Nomenclature
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11
2.3
Physical
and
Chemical
Properties
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13
3.0
Metabolism
Assessment
.
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14
3.1
Comparative
Metabolic
Profile
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14
3.2
Nature
of
the
Residue
in
Foods
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15
3.2.1.
Description
of
Primary
Crop
Metabolism
.
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15
3.2.2
Description
of
Livestock
Metabolism
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16
3.2.3
Description
of
Rotational
Crop
Metabolism,
including
identification
of
major
metabolites
and
specific
routes
of
biotransformation
.
.
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17
3.3
Environmental
Degradation
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17
3.4
Tabular
Summary
of
Metabolites
and
Degradates
.
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18
3.5
Toxicity
Profile
of
Major
Metabolites
and
Degradates
.
.
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20
3.6
Summary
of
Residues
for
Tolerance
Expression
and
Risk
Assessment
.
.
.
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20
3.6.1
Tabular
Summary
.
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20
3.6.2
Rationale
for
Inclusion
of
Metabolites
and
Degradates
.
.
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.
21
4.0
Hazard
Characterization/
Assessment
.
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21
4.1
Hazard
Characterization
.
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21
4.1.1.
Database
Summary
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21
4.1.1.1.
Studies
available
and
considered
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21
4.1.1.2.
Mode
of
action,
metabolism
and
toxicokinetic
data
.
.
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22
4.1.1.3.
Sufficiency
of
studies/
data
.
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22
4.1.2.
Toxicological
effects
.
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22
4.1.3.
Dose
response
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24
4.1.4.
FQPA
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24
4.1.5.
Acute
Toxicity
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24
4.1.6.
Sub­
chronic/
Chronic
and
Other
Toxicity
.
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25
4.2
FQPA
Hazard
Considerations
.
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27
4.2.1
Adequacy
of
the
Toxicity
Data
Base
.
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27
4.2.2
Evidence
of
Neurotoxicity
.
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28
4.2.3
Developmental
Toxicity
Studies
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28
4.2.4
Reproductive
Toxicity
Study
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30
4.2.5
Additional
Information
from
Literature
Sources
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30
4.2.6
Pre­
and/
or
Postnatal
Toxicity
.
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30
4.2.6.1
Determination
of
Susceptibility
.
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30
4.2.6.2
Degree
of
Concern
Analysis
and
Residual
Uncertainties
for
Page
3
of
68
Pre
and/
or
Post­
natal
Susceptibility
.
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31
4.3
Recommendation
for
a
Developmental
Neurotoxicity
Study
.
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31
4.3.1
Evidence
that
supports
requiring
a
Developmental
Neurotoxicity
study
.
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31
4.3.2
Evidence
that
supports
not
requiring
a
Developmental
Neurotoxicity
study
.
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31
4.3.3
Rationale
for
the
UF
DB
(
when
a
DNT
is
recommended)
.
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31
4.4
Hazard
Identification
and
Toxicity
Endpoint
Selection
.
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31
4.4.1
Acute
Reference
Dose
(
aRfD)
­
Females
age
13­
49
.
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31
4.4.2
Acute
Reference
Dose
(
aRfD)
­
General
Population
.
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31
4.4.3
Chronic
Reference
Dose
(
cRfD)
.
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32
4.4.4
Incidental
Oral
Exposure
(
Short
and
Intermediate
Term)
.
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33
4.4.5
Dermal
Absorption
.
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34
4.4.6
Dermal
Exposure
(
Short,
Intermediate
and
Long
Term)
.
.
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34
4.4.7
Inhalation
Exposure
(
Short,
Intermediate
and
Long
Term)
.
.
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35
4.4.8
Margins
of
Exposure
.
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36
4.4.9
Recommendation
for
Aggregate
Exposure
Risk
Assessments
.
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36
4.4.10
Classification
of
Carcinogenic
Potential
.
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36
4.5
Special
FQPA
Safety
Factor
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38
4.6
Endocrine
disruption
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38
5.0
Public
Health
Data
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39
5.1
Incident
Reports
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39
5.2
Other
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40
6.0
Exposure
Characterization/
Assessment
.
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40
6.1
Dietary
Exposure/
Risk
Pathway
.
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40
6.1.1
Residue
Profile
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40
6.1.2
Chronic
Dietary
Exposure
and
Risk
.
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43
6.2
Water
Exposure/
Risk
Pathway
.
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44
6.3
Residential
(
Non­
Occupational)
Exposure/
Risk
Pathway
.
.
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46
6.3.1
Residential
Handler
Exposures
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46
6.3.1.1
Residential
Handler
Exposure
Scenarios
.
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47
6.3.1.2
Data
and
Assumptions
For
Residential
Handler
Exposure
Scenarios
.
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47
6.3.1.3
Residential
Handler
Exposure
and
Risk
Estimates
.
.
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.
48
6.3.2
Residential
Postapplication
Exposures
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50
6.3.2.1
Residential
Postapplication
Exposure
Scenarios
.
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50
6.3.2.2
Data
&
Assumptions
for
Residential
Postapplication
Exposure
Scenarios
.
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51
6.3.2.3
Residential
Postapplication
Exposure
and
Risk
Estimates
53
6.3.3
Other
(
Spray
Drift,
etc.)
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54
Page
4
of
68
7.0
Aggregate
Risk
Assessments
and
Risk
Characterization
.
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54
7.1
Acute
Aggregate
Risk
.
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55
7.2
Short­
Term
Aggregate
Risk
.
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55
7.3
Intermediate­
Term
Aggregate
Risk
.
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58
7.4
Long­
Term
Aggregate
Risk
.
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58
7.5
Cancer
Risk
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58
8.0
Cumulative
Risk
Characterization/
Assessment
.
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58
9.0
Occupational
Exposure/
Risk
Pathway
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58
10.0
Data
Needs
and
Label
Requirements
.
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58
10.1
Toxicology
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58
10.2
Residue
and
Product
Chemistry
Deficiencies
.
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58
10.3
Occupational
and
Residential
Exposure
.
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59
References:
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59
Appendices
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61
Page
5
of
68
1.0
Executive
Summary
The
Health
Effects
Division
(
HED)
of
EPA's
Office
of
Pesticide
Programs
has
evaluated
the
toxicity
and
exposure
data
bases
for
the
pesticide
active
ingredient
imazaquin,
including
its
ammonium
and
monosodium
salts,
and
has
conducted
a
human
health
risk
assessment
in
support
of
the
Tolerance
Reassessment
Eligibility
Decision
(
TRED)
for
this
active
ingredient.

Use
Information
Imazaquin
is
an
imidazolinone
herbicide
which
controls
weeds
by
inhibiting
the
synthesis
of
specific
amino
acids
(
valine,
leucine
&
isoleucine)
necessary
for
plant
growth.
It
is
registered
as
a
pre­
plant,
preemergence
and
early
postemergence
herbicide
for
use
on
soybeans,
primarily
across
the
central
Midwest
from
Kentucky
to
Illinois
and
across
the
mid­
South
in
Arkansas,
Louisiana
and
Mississippi.
It
is
also
registered
for
pre­
and
postemergence
weed
control
on
ornamentals
and
warm
season
turfgrass
in
both
residential
and
non­
residential
settings.
The
turf
and
ornamental
uses
are
concentrated
across
the
southern
U.
S.
because
of
imazaquin's
lack
of
selectivity
on
cool
season
grasses.

Toxicology
Hazard:
The
available
toxicity
data
on
imazaquin
are
adequate
to
assess
the
chemical's
hazard
potential.
Technical
imazaquin
has
low
(
category
III/
IV)
acute
toxicity
via
the
oral,
dermal
and
inhalation
routes
of
exposure.
It
is
non­
irritating
to
the
eye
(
category
IV)
and
only
mildly
irritating
to
the
skin.
Imazaquin
did
not
cause
dermal
sensitization
in
the
guinea
pig.

Overall,
imazaquin
appears
to
cause
subchronic
and
chronic
toxicity
only
at
higher
doses,
with
few
clinical
signs
identified
in
rats,
mice,
dogs
or
rabbits.
Toxicity
was
similar
in
both
male
and
female
test
animals,
with
the
dog
being
the
most
sensitive
species
to
imazaquin
exposure.
The
most
commonly
observed
clinical
sign
in
the
chronic
studies
was
decreased
body
weight,
which
was
seen
in
both
mice
and
dogs.
In
the
chronic
dog
study,
additional
effects
were
noted
at
the
LOAEL
of
125
mg/
kg/
day,
including
slight
anemia
indicated
by
changes
in
hematology
parameters,
changes
to
clinical
chemistry
and
skeletal
muscle
myopathy
at
necropsy
in
both
sexes.
No
effects
were
observed
at
the
highest
dose
tested
(
500
mg/
kg/
day)
in
the
rat
combined
chronic
toxicity/
carcinogenicity
study;
nor
were
systemic
effects
seen
at
the
highest
dose
tested
(
1000
mg/
kg/
day)
in
the
rabbit
21­
day
dermal
toxicity
study.

The
database
is
considered
adequate
to
characterize
any
potential
pre­
and/
or
post­
natal
risk
to
infants
and
children.
Additional
studies
are
not
required.
In
the
developmental
study
in
rats,
treatment­
related
effects
on
fetal
body
weight
and
reduced
ossification
were
observed,
but
only
at
the
dose
where
maternal
toxicity
occurred.
No
treatment­
related
effects
on
fetuses
were
seen
in
the
rabbit
developmental
toxicity
study;
and
in
the
rat
reproductive
study,
no
toxicity
in
either
the
parents
or
offspring
was
noted
at
the
highest
dose
tested.
Based
on
these
studies,
there
is
no
indication
of
increased
susceptibility
of
fetuses
or
offspring
to
imazaquin.
Since
there
is
no
Page
6
of
68
increased
risk
to
infants
and
children
and
no
residual
uncertainty,
the
special
FQPA
Safety
Factor
may
be
reduced
to
1X.

No
evidence
of
neurotoxicity
was
observed
in
any
study.
Based
on
the
weight
of
evidence,
a
developmental
neurotoxicity
(
DNT)
study
is
not
required
for
imazaquin.

No
evidence
of
carcinogenicity
was
seen
in
mice
or
rats,
and
imazaquin
was
non­
mutagenic
in
available
mutagenicity
tests.
Mice
were
dosed
up
to
600
mg/
kg/
day
for
18
months,
and
rats
were
fed
up
to
500
mg/
kg/
day
for
2
years
without
any
evidence
of
a
treatment­
related
increased
incidence
of
tumors.
Imazaquin
was
non­
mutagenic
in
the
Ames
test
and
demonstrated
negative
responses
in
the
in
vitro
cell
transformation
assay,
a
cytogenetics
study
with
HGPRT
in
Chinese
hamster
cells
and
an
unscheduled
DNA
synthesis
assay.

Toxicity
Endpoint/
Dose
Selection:
A
chronic
reference
dose
(
cRfD)
of
0.25
mg/
kg/
day
was
established
for
imazaquin,
based
on
the
NOAEL
of
25
mg/
kg/
day
in
the
dog
chronic
toxicity
study
and
an
uncertainty
factor
of
100
(
10x
for
interspecies
extrapolation
and
10x
for
intraspecies
variation).
Effects
seen
at
the
LOAEL
included
body
weight
loss,
clinical
chemistry/
hematology
differences,
slight
anemia
and
skeletal
muscle
myopathy.
Body
weight
decreases
occurred
in
the
first
4
weeks
of
the
study;
and
the
hematology
data
from
the
earliest
assessment
at
13
weeks
indicated
statistically
significant
changes
in
hematology
parameters,
raising
concern
that
the
anemia
effects
of
imazaquin
may
occur
within
a
short
or
intermediate
time
frame.
Therefore,
the
NOAEL
of
25
mg/
kg/
day
from
this
study
was
selected
to
assess
oral,
dermal
and
inhalation
exposures
of
short­,
intermediate­
and
long­
term
duration.
An
acute
reference
dose
(
aRfD)
was
not
established,
since
an
endpoint
attributable
to
a
single
exposure
was
not
identified
from
the
available
database.

Residue
Chemistry
A
tolerance
has
been
established
under
40
CFR
§
180.426
for
residues
of
imazaquin
in
or
on
soybeans
at
0.05
ppm.
The
available
residue
chemistry
data
are
adequate
to
support
the
existing
tolerance
and
to
assess
human
dietary
exposure
to
imazaquin
from
the
consumption
of
treated
food
commodities.
The
residue
of
concern
in
soybeans
for
tolerance
enforcement
and
risk
assessment
purposes
is
imazaquin,
per
se.
Based
on
the
findings
of
the
livestock
metabolism
studies,
where
livestock
were
dosed
at
94x
(
ruminant)
and
68x
(
poultry)
the
maximum
theoretical
dietary
burden,
HED
has
determined
that
40
CFR
§
180.6(
a)(
3)
is
applicable
to
imazaquin;
there
is
no
reasonable
expectation
of
finite
residues
in
ruminants
or
poultry.
Adequate
analytical
methods
are
available
for
the
enforcement
of
the
imazaquin
tolerance.

Environmental
Fate
The
available
environmental
fate
data
are
adequate
to
assess
the
residues
of
concern
in
drinking
water.
Imazaquin
is
an
imidazole
compound
that
is
highly
mobile
and
non­
volatile.
In
terrestrial
Page
7
of
68
environments
it
is
persistent;
and
in
aquatic
environments,
imazaquin
is
stable
to
hydrolysis
at
all
pH
levels.

No
major
degradates
(
i.
e.,
>
10
%
of
the
applied
dose)
were
identified
in
the
aerobic
soil
metabolism
study.
The
most
significant
degradation
occurred
in
the
aqueous
photolysis
study.
The
major
photolytic
degradates
(>
10%
of
the
applied
dose),
in
addition
to
CO
2
,
were
3­
quinolinecarboxylic
acid;
2,3­
quinolinecarboxylic
acid
imide;
2,3­
dihydro­
3­
imino­
1H­
pyrrolo­
[
3,4b]
quinolin­
1­
one;
and
2,3­
quinolinedicarboxylic
acid.
Specific
toxicity
data
are
not
available
for
these
compounds;
however,
based
on
their
structural
similarity
to
the
parent,
the
risk
assessment
team
has
concluded
that
they
may
have
toxicity
similar
to
parent
imazaquin
and
should,
therefore,
be
included
in
the
dietary
risk
assessment.
These
photolytic
degradates
are
not
expected
to
form
in
drinking
water
from
ground
water
sources;
therefore,
the
residue
of
concern
in
drinking
water
from
ground
water
sources
is
imazaquin,
per
se.

Dietary
Exposure
A
chronic
dietary
risk
assessment
was
conducted
for
imazaquin,
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM­
FCID,
Version
2.03).
Since
no
toxic
effects
attributable
to
a
single
exposure
have
been
identified
for
imazaquin,
an
acute
dietary
exposure
assessment
was
not
conducted.
Also,
since
there
is
no
evidence
that
imazaquin
is
carcinogenic
to
humans,
a
dietary
cancer
assessment
was
not
conducted.

The
tier
1
chronic
assessment
assumed
that
100%
of
the
soybean
crop
is
treated
and
that
residues
of
imazaquin
are
present
at
the
tolerance
level
of
0.05
ppm
in
all
soybean
commodities,
including
processed
commodities.
Drinking
water
was
incorporated
directly
into
the
dietary
assessment
using
the
tier
1
estimated
drinking
water
concentration
for
ground
water
generated
by
the
SCIGROW
model.

The
resulting
dietary
exposure
estimates
are
well
below
HED's
level
of
concern
(
i.
e.,
<
100%
of
the
cPAD).
Chronic
dietary
exposure
is
estimated
to
be
less
than
1%
of
the
cPAD
for
the
U.
S.
population
and
all
population
subgroups.
More
than
95%
of
the
total
estimated
dietary
exposure
is
from
drinking
water.

Residential
Exposure
There
is
a
potential
for
exposure
in
residential
settings
during
the
application
process
for
homeowners
who
use
products
containing
imazaquin
on
turf
and
ornamentals.
There
is
also
a
potential
for
exposure
of
children
and
adults
who
enter
residential
areas
previously
treated
with
imazaquin.
In
both
cases,
the
duration
of
exposure
is
expected
to
be
short­
term
only.
As
a
result,
short­
term
risk
assessments
have
been
completed
for
both
residential
handler
and
postapplication
scenarios.
The
routes
of
exposure
considered
in
the
assessments
included
inhalation
(
residential
handler
exposure
only),
dermal
(
residential
handler
and
postapplication
exposures)
and
incidental
oral
(
post­
application
exposure
for
children
only).
Page
8
of
68
Chemical­
specific
exposure
data
are
not
available
for
imazaquin.
Residential
handler
exposure
was
assessed
using
the
Pesticide
Handlers
Exposure
Database
(
PHED
ver.
1.1)
and
data
from
the
Outdoor
Residential
Exposure
Task
Force
(
ORETF).
The
residential
handler
and
postapplication
assessments
were
conducted
in
accordance
with
the
EPA's
draft
Standard
Operating
Procedures
for
Residential
Exposure
Assessments
(
R­
SOPs)
adopted
December
18,
1997
and
revised
on
February
22,
2001.

The
Margin
of
Exposure
(
MOE)
of
concern
for
residential
exposures
is
100.
The
combined
dermal
and
inhalation
MOEs
for
residential
handlers
range
from
1,700
(
homeowners
applying
liquid
concentrates
to
turf
using
a
hose­
end
sprayer)
to
15,400
(
homeowners
applying
liquid
concentrates
to
ornamentals
with
a
hand
held
pump).
Postapplication
MOEs
for
adults
range
from
430
(
high
contact
turf
scenario,
i.
e.,
"
jazzercize")
to
12,500
(
mowing
turf).
The
combined
postapplication
dermal
and
incidental
oral
(
including
hand­
to­
mouth,
object­
to­
mouth
and
incidental
soil
ingestion
exposures)
MOE
for
children
playing
on
treated
turf
is
260.
The
residential
handler
and
postapplication
exposure
MOEs
are
all
greater
than
100
and
are,
therefore,
not
of
concern.

Aggregate
Risk
Short­
and
long­
term
(
chronic)
aggregate
risk
assessments
were
conducted
for
imazaquin.
The
short­
term
assessment
considered
both
dietary
(
food
+
water)
and
residential
exposures.
The
long­
term
assessment
considered
dietary
exposure
only,
since
the
current
uses
of
imazaquin
are
not
expected
to
result
in
long­
term
residential
exposure.
An
intermediate­
term
aggregate
assessment
was
not
conducted,
since
the
current
uses
of
imazaquin
are
not
expected
to
result
in
exposures
of
this
duration.
Also,
since
an
endpoint
attributable
to
a
single
exposure
was
not
identified
for
imazaquin,
an
acute
aggregate
assessment
was
not
conducted.

The
results
of
the
deterministic,
tier
1
dietary
assessment
indicate
that
the
chronic
aggregate
exposure
to
imazaquin
from
food
and
water
is
well
below
HED's
level
of
concern,
with
estimated
exposures
representing
<
1%
of
the
cPAD
for
the
U.
S.
population
and
all
population
subgroups,
including
infants
and
children.
When
the
chronic
dietary
exposure
is
combined
with
short­
term
residential
exposure,
the
resulting
short­
term
aggregate
risk
estimates
for
adults
and
children
are
also
below
HED's
level
of
concern.
The
MOE
of
concern
for
short­
term
aggregate
risk
is
100.
Since
the
estimated
short­
term
aggregate
risk
MOEs
for
adults
and
children
(
toddlers)
are
340
and
257,
respectively,
short­
term
aggregate
risk
is
not
considered
to
be
of
concern
for
imazaquin.

Occupational
Exposure
An
occupational
exposure
assessment
is
not
required
to
reassess
tolerances
under
FQPA;
since
this
risk
assessment
is
being
conducted
solely
for
tolerance
reassessment
purposes,
an
occupational
exposure
assessment
has
not
been
conducted.

Conclusions/
Risk
Characterization
Page
9
of
68
Imazaquin
is
a
relatively
low
toxicity
pesticide
whose
potential
routes
of
exposure
include
food,
drinking
water
and
residential
areas.
Under
the
conditions
of
its
current
use,
estimated
health
risks
to
the
general
population
are
below
HED's
level
of
concern.
Estimated
aggregate
risk
MOEs
from
the
consumption
of
food
and
drinking
water
and
from
exposure
to
the
pesticide
in
residential
settings
exceed
100
for
all
populations,
including
infants
and
children,
and,
therefore,
are
not
of
concern.

The
aggregate
risk
assessment
for
imazaquin
is
a
screening
level
assessment
which
is
based
on
high­
end
residential
and
dietary
exposure
estimates.
Residues
in
food
are
assumed
to
be
present
at
the
maximum
tolerance
level,
and
100%
of
the
soybean
crop
is
assumed
to
be
treated
with
imazaquin.
The
drinking
water
assessment
utilizes
values
generated
by
models
using
modeling
parameters
which
are
designed
to
provide
conservative,
health
protective,
high­
end
estimates
of
drinking
water
concentrations.
The
residential
exposure
assessment
is
conducted
in
accordance
with
HED's
residential
SOPs,
which
also
provide
conservative,
screening­
level
estimates
of
exposure.
In
addition,
the
short­
term
aggregate
assessment
for
adults
assumes
that
dietary,
residential
handler
and
residential
postapplication
exposures
occur
simultaneously
over
a
short
period
of
time
(
1
to
30
days),
which,
although
possible,
is
unlikely.

Finally,
the
aggregate
risk
assessment
includes
estimated
risks
from
dermal
exposure
to
imazaquin.
As
discussed
in
section
4.4.6
(
Dermal
Exposure
(
Short,
Intermediate
and
Long
Term)),
the
decision
to
conduct
a
dermal
assessment
was
based
on
highly
conservative
assumptions
that
may
be
revisited
for
future
imazaquin
risk
assessments.
If
estimates
of
dermal
exposure
were
excluded
from
the
aggregate
assessment,
estimated
aggregate
exposure
and
risk
for
both
children
and
adults,
while
already
below
HED's
level
of
concern,
would
be
even
lower.

For
these
reasons,
HED
has
a
high
level
of
confidence
that
this
screening
level
aggregate
assessment
for
imazaquin
does
not
underestimate
human
health
risks
from
the
currently
registered
uses
of
imazaquin.

2.0
Ingredient
Profile
Imazaquin
[
±
­
2­(
4,5­
Dihydro­
4­
methyl­
4­(
1­
methylethyl)­
5­
oxo­
1H­
imidazol­
2­
yl)­
3­
quinolinecarboxylic
acid]
is
a
broad
spectrum,
pre­
plant,
preemergence
or
postemergence
herbicide
belonging
to
the
imidazolinone
class
of
pesticides.
It
controls
weeds
by
inhibiting
the
synthesis
of
specific
amino
acids
(
valine,
leucine
&
isoleucine)
necessary
for
plant
growth.
Imazaquin
is
formulated
as
an
acid,
ammonium
salt
or
sodium
salt
and
registered
for
food
use
on
soybeans,
as
well
as
non­
food
use
on
warm
season
turfgrass
and
ornamentals
in
both
residential
and
non­
residential
settings.
Applications
in
residential
settings
may
be
made
by
both
commercial
applicators
and
homeowners.
Page
10
of
68
2.1
Summary
of
Registered
Uses
The
registered
imazaquin
formulation
types
include
water
dispersible
granule
(
WDG),
wettable
powder
(
WP),
emulsifiable
concentrate
(
EC)
and
soluble
concentrate
(
SC).
The
active
ingredient
(
as
acid
equivalent)
in
the
end­
use
products
ranges
from
0.71%
to
70%.
On
soybeans,
a
maximum
of
0.25
lb.
acid
equivalent
(
ae)/
acre
may
be
applied
per
year
using
ground
or
aerial
equipment.
The
maximum
single
application
rate
is
0.125
lb.
ae/
acre.
All
product
labels
indicate
a
pre­
harvest
interval
(
PHI)
of
90
days
for
soybeans.
Imazaquin
may
be
applied
to
turf
and
ornamentals
at
up
to
0.5
lb.
ae/
acre
by
commercial
applicators
and
up
to
0.38
lb.
ae/
acre
by
homeowners.
The
Restricted
Entry
Interval
(
REI)
for
agricultural
uses
is
12
hours.

A
tabular
summary
of
the
registered
uses
of
imazaquin
is
presented
in
Table
2.1.

TABLE
2.1.
Directions
For
Use
of
Imazaquin
Application
Timing
°
Application
Type
Max.
Single
Application
Rate
Max.
Seasonal
Rate
Max.
No.
Applications/
cc
&
yr
Restrictions
SOYBEANS
Pre­
plant,
Preemergence,
Postemergence,
Early
Postemergence
°
Broadcast,
Soil
Incorporated
°
Ground,
Aerial
0.125
lb
ae/
A
0.25
lb
ae/
A
(
EPA
Reg.
No.
241­
292)
2
°
90
day
preharvest
interval
°
Do
not
graze
or
feed
treated
soybean
forage,
hay,
or
straw
to
livestock
°
Do
not
apply
through
any
type
of
irrigation
system.
°
Rotational/
plant
back
crop
restriction.
°
Geographic
restrictions.

TURFGRASS
(
RESIDENTIAL
AND
NON­
RESIDENTIAL)/
ORNAMENTALS
Preemergence,
Postemergence
°
Ground
broadcast
°
Spot
Application
0.375
­
0.5
lb.
ae/
A
0.375
­
0.5
lb.
ae/
A
1
to
2
°
Do
not
apply
aerially.
°
Do
not
graze
or
feed
clippings
of
treated
turfgrass.
°
Do
not
apply
through
any
type
of
irrigation
system.
Page
11
of
68
N
N
H
N
OH
O
O
CH
3
CH(
CH
3
)
2
N
N
H
N
O
O
O
CH
3
CH(
CH
3
)
2
NH
4
+
2.2
Structure
and
Nomenclature
TABLE
2.2.
Imazaquin
(
and
its
Salts)
Nomenclature
Chemical
Structure
Common
name
Imazaquin
Molecular
Formula
C17H17N3O3
Molecular
Weight
311.34
IUPAC
name
(
RS)­
2­(
4­
isopropyl­
4­
methyl­
5­
oxo­
2­
imidazolin­
2­
yl)
quinoline­
3­
carboxylic
acid
CAS
name
±
­
2­(
4,5­
Dihydro­
4­
methyl­
4­(
1­
methylethyl)­
5­
oxo­
1H­
imidazol­
2­
yl)­
3­
quinolinecarboxylic
acid
CAS
Registry
Number
81335­
37­
7
PC
Code
128848
Chemical
Class
Imidazolinone
Chemical
structure
Common
name
Imazaquin,
ammonium
salt
IUPAC
name
(
RS)­
2­(
4­
isopropyl­
4­
methyl­
5­
oxo­
2­
imidazolin­
2­
yl)
quinoline­
3­
carboxylic
acid,
monoammonium
salt
CAS
name
2­[
4,5­
dihydro­
4­
methyl­
4­(
1­
methylethyl)­
5­
oxo­
1H­
imidazol­
2­
yl]­
3­
quinolinecarboxylic
acid,
monoammonium
salt
CAS
#
81335­
47­
9
PC
Code
128840
TABLE
2.2.
Imazaquin
(
and
its
Salts)
Nomenclature
Page
12
of
68
N
N
H
N
O
O
O
CH
3
CH(
CH
3
)
2
Na
+
Chemical
structure
Common
name
Imazaquin,
sodium
salt
IUPAC
name
(
RS)­
2­(
4­
isopropyl­
4­
methyl­
5­
oxo­
2­
imidazolin­
2­
yl)
quinoline­
3­
carboxylic
acid,
monosodium
salt
CAS
name
2­[
4,5­
dihydro­
4­
methyl­
4­(
1­
methylethyl)­
5­
oxo­
1H­
imidazol­
2­
yl]­
3­
quinolinecarboxylic
acid,
monosodium
salt
CAS
#
81335­
46­
8
PC
Code
129023
End­
use
products
(
EPs):

End­
use
products
(
EPs)
Formulation1,2
Product
Name
There
are
twelve
active
end­
use
products
(
EPs)
containing
imazaquin
for
use
on
soybeans.
Seven
of
the
products
contain
the
imazaquin
acid,
four
contain
the
ammonium
salt
of
imazaquin,
and
one
contains
the
sodium
salt
of
imazaquin.
All
products
are
registered
to
BASF
Corp.
Additionally,
there
are
three
SLN
registrations.

Imazaquin
(
PC
Code
128848)

241­
3063
70%
WDG
Scepter
®
70
DG
Herbicide
241­
361
5.4%
SC
Detail
®
Herbicide
241­
369
35%
WDG
Imazaquin/
Imazathapyr
DG
241­
376
1.9%
EC
Steel
®
Herbicide
241­
407
2.8%
EC
Backdraft
 
Herbicide
241­
408
70%
WP
Backdraft
 
CP
241­
415
1.7%
SC
Backdraft
 
SL
Herbicide
LA010010
70%
WDG
Scepter
®
70
DG
Herbicide
MS010011
2.8%
EC
Backdraft
 
Herbicide
MS020002
1.7%
SC
Backdraft
 
SL
Herbicide
Ammonium
salt
of
imazaquin
(
PC
Code
128840)

241­
307
4.72%
EC
(
4.48%
ae)
TRI­
SCEPT
®

241­
289
17.3%
SC
(
16.4%
ae)
Scepter
®

241­
292
17.3%
SC
(
16.4%
ae)
Scepter
®

241­
327
3.65%
SC
(
3.46%
ae)
Squadron
®
TABLE
2.2.
Imazaquin
(
and
its
Salts)
Nomenclature
Page
13
of
68
Sodium
salt
of
imazaquin
(
PC
Code
129023)

241­
321
5.61%
SC
(
5.24%
ae)
Scepter
O.
T
®

There
are
five
active
end­
use
products
(
EPs)
containing
imazaquin
for
use
on
turf
and
ornamentals.
One
of
the
products
contains
the
imazaquin
acid
and
four
contain
the
ammonium
salt
of
imazaquin.
All
are
registered
to
BASF
Corp.,
except
one,
which
is
registered
to
Ambrands.

Imazaquin
(
PC
Code
128848)

241­
303
17.3%
SC
Image
®
1.5
LC
Herbicide
Ammonium
salt
of
imazaquin
(
PC
Code
128840)

241­
319
70%
WDG
(
66.4%
ae)
Image
®
70
DG
241­
326
0.79%
SC
(
0.75%
ae)
Timeout
 
Grass
Growth
Regulator
and
Weed
Killer
241­
352
0.75%
SC
(
0.71%
ae)
Timeout
®
Plus
Herbicide
73342­
4
3.3%
SC
(
3.14%
ae)
Image
®
Herbicide
Consumer
Concentrate
1
WDG
­
water
dispersiable
granule;
SC
­
soluble
concentrate;
EC
­
emulsifiable
concentrate;
WP
=
wettable
powder
2
ae
=
acid
equivalent
3
The
registrant
has
indicated
that
the
only
product
currently
being
marketed
for
use
on
soybeans
is
Scepter
70
DG
(
EPA
Reg.
No.
241­
306).
However,
all
products
with
active
registrations
are
presented
in
this
document.

2.3
Physical
and
Chemical
Properties
TABLE
2.3
Physicochemical
Properties
of
Imazaquin
Parameter
Value
Reference
Melting
point
219­
224
°
C
(
decomposes)
MRID
00146197;
PP#
5F3273,
RCB
#
1265,
1/
9/
86,
A.
Smith
pH
4.6
at
25
°
C
Density,
bulk
density,
or
specific
gravity
0.39
g/
mL
untapped;
0.43
g/
mL
tapped
Water
solubility
at
25
°
C
60
ppm
Solvent
solubility
g/
100
mL
Acetone
0.30
DMF
6.80
DMSO
15.9
Ethanol
0.30
Heptane
0.02
Methanol
0.50
Methylene
chloride
1.36
Toluene
0.04
Vapor
pressure
<
2
x
10­
8
mm
Hg
at
45
°
C
TABLE
2.3
Physicochemical
Properties
of
Imazaquin
Parameter
Value
Reference
Page
14
of
68
Dissociation
constant,
pKa
3.8
Octanol/
water
partition
coefficient
2.2
at
22
°
C
UV/
visible
absorption
spectrum
Not
available
3.0
Metabolism
Assessment
3.1
Comparative
Metabolic
Profile
Imazaquin
is
rapidly
absorbed
and
excreted
by
the
rat
following
oral
administration.
In
the
rat
metabolism
study,
essentially
all
(
102%)
of
the
administered
radioactivity
was
recovered
within
48
hours
of
treatment.
The
majority
(
94%)
was
recovered
in
the
urine,
with
4%
recovered
in
the
feces
and
4%
recovered
in
the
cage
wash.
Twenty­
four
hours
after
treatment,
residual
radioactivity
was
detected
in
the
liver
(
0.025
ppm)
and
kidney
(
0.17
ppm);
however,
by
48
hours,
the
concentration
in
all
tissues
was
at
or
below
the
limit
of
detection
(
0.01
ppm).
Analysis
of
urine
collected
24
and
48
hours
after
treatment
showed
that
99.7%
of
the
recovered
radioactivity
was
unchanged
parent
compound,
indicating
that
imazaquin
is
poorly
metabolized
in
the
rat.

The
results
of
ruminant
and
poultry
metabolism
studies
suggest
that
imazaquin
may
also
be
poorly
metabolized
in
other
animal
species.
In
the
ruminant
metabolism
study,
total
radioactive
residues
(
TRR)
were
nondetectable
in
milk
(<
0.01
ppm)
and
all
tissues
(<
0.05
ppm)
of
lactating
goats
following
oral
administration
of
[
14C]
imazaquin
for
seven
consecutive
days.
Similarly,
in
the
poultry
metabolism
study,
TRR
were
nondetectable
(<
0.05
ppm)
in
egg
white,
egg
yolk,
muscle,
liver,
kidney,
skin
and
fat
of
laying
hens
following
oral
administration
of
[
14C]
imazaquin
for
seven
consecutive
days.
The
TRR
in
urine
and
feces
were
not
measured
in
these
studies;
however,
the
lack
of
radioactive
residues
in
milk
and
animal
tissues
suggests
that
imazaquin
is
rapidly
absorbed
and
excreted
in
livestock,
as
it
is
in
the
rat.

The
results
of
soybean
and
corn
metabolism
studies
indicate
that
imazaquin
is
much
more
extensively
metabolized
in
plants.
Soybean
metabolism
studies
using
both
carboxyl
and
benzene
labeled
imazaquin
indicate
that
imazaquin
is
extensively
degraded
and
reincorporated
into
native
plant
constituents.
TRRs
in
soybean
seed
and
mature
hulls
were
all
<
0.05
ppm.
The
TRR
on
mature
foliage
ranged
from
0.05
to
0.66
ppm.
Total
radioactivity
from
1
month
up
to
maturity
was
similar
between
the
carboxyl
and
benzene
labeled
imazaquin,
indicating
that
loss
of
CO
2
from
the
carboxylic
acid
moiety
is
not
a
major
degradation
route.
The
residues
were
not
chemically
identified;
however,
characterization
of
the
protein
portion
of
the
soybean
seed
indicates
that
a
significant
amount
of
the
TRR
had
been
reincorporated
into
naturally
occurring
protein
components.
Characterization
of
radioactivity
on
foliage
and
straw
indicates
the
presence
of
several
metabolites
(
each
<
0.01
to
0.02
ppm),
with
no
parent
compound
present.

A
field
corn
metabolism
study
indicates
that
imazaquin
is
extensively
degraded
in
mature
plant
commodities.
The
proposed
metabolic
pathway
of
imazaquin
applied
to
corn
is
as
follows:
(
i)
Page
15
of
68
direct
conjugation
of
the
parent
chemical;
(
ii)
hydroxylation
of
the
parent
chemical
to
its
5­
hydroxy
metabolite
(
CL
343,684)
followed
by
conjugation;
and
(
iii)
degradation
of
the
imidazoline
ring
system
to
quinoline­
2,3­
dicarboxylic
acid
(
CL
263,875)
followed
by
conjugation.
Plant
residues,
although
substantive
in
the
early
growth
stages,
are
comprised
of
a
variety
of
metabolites
which
decline
in
content
to
<
0.01
ppm
in
mature
field
corn
commodities.

In
the
environment,
imazaquin
is
stable
to
anaerobic
soil
metabolism
and
hydrolysis;
however,
significant
degradation
occurs
by
aqueous
photolysis.
Based
on
a
submitted
study,
the
major
photolytic
degradates,
in
addition
to
CO
2
,
were
3­
quinolinecarboxylic
acid,
2,3­
quinolinecarboxylic
acid
imide,
2,3­
dihydro­
3­
imino­
1H­
pyrrolo­[
3,4b]
quinolin­
1­
one,
and
2,3­
quinolinedicarboxylic
acid.
There
were
18
unidentified
minor
degradates.

3.2
Nature
of
the
Residue
in
Foods
3.2.1.
Description
of
Primary
Crop
Metabolism
The
qualitative
nature
of
the
residue
in
plants
is
understood
for
the
use
of
imazaquin
on
soybeans.
Available
plant
metabolism
data
for
imazaquin
are
summarized
below:

Soybean:
Soybean
metabolism
studies
were
conducted
in
Florida
and
New
Jersey
using
postemergence
and
pre­
plant
incorporated
treatment
methods.
Both
sites
used
carboxyl
labeled
imazaquin
as
the
test
substance.
The
New
Jersey
site
also
used
benzene
labels;
however,
not
all
of
the
benzene
results
were
submitted.
Diisopropyl­
amine
salt
of
imazaquin
was
applied
to
all
test
plots
at
a
rate
of
0.38
lb
ai/
A
(
1.5x).
For
the
post­
emergence
trials,
the
test
substance
was
applied
at
the
trifoliate
leaf
stage.
For
the
pre­
plant
incorporated
trials,
the
test
substance
was
applied
to
the
soil
and
incorporated
2
inches.
Plants
were
harvested
at
intervals
of
one
week
to
6.5
months,
dividing
the
more
mature
samples
into
fodder,
hulls,
and
seed.

For
preplant
application
the
soybean
seed
had
total
radioactivity
residue
(
TRR)
of
0.01
to
0.02
ppm
(
14C­
carboxyl
label)
and
0.03
ppm
(
14C­
benzene
label).
The
foliage
had
radioactivity
at
0.43
to
0.50
ppm
at
one
month;
0.05
ppm
to
0.09
ppm
at
2
months;
and
0.07
ppm
to
0.12
ppm
in
mature
foliage.
The
mature
hulls
had
TRR
at
0.04
ppm.

For
early
postemergence
application
soybean
seed
had
TRR
of
0.01
ppm
to
0.05
ppm
(
14Ccarboxyl
label)
and
0.04
ppm
(
14C­
benzene
label).
The
TRR
on
foliage
was
0.24
to
0.60
ppm
at
one
month
and
0.19
to
0.66
ppm
in
mature
foliage.

Total
radioactivity
from
1
month
up
to
maturity
was
similar
between
the
carboxyl
and
benzene
labeled
imazaquin,
indicating
that
loss
of
CO
2
from
the
carboxylic
acid
moiety
is
not
a
major
degradation
route,
since
residues
from
the
carboxyl
label
should
be
considerably
lower
in
that
case.
Page
16
of
68
The
residues
were
not
chemically
identified;
however,
some
characterization
involving
the
carboxyl
label
was
accomplished
by
solvent
fractionation
of
the
activity
and
isolation
of
the
protein
portion
of
the
seed.
HED
determined
that
the
characterization
was
adequate
to
show
that
imazaquin
was
extensively
degraded
and
reincorporated
into
native
plant
parts.

The
characterization
of
radioactivity
on
foliage
or
straw
was
not
presented
in
the
study
report.
At
a
preregistration
conference
on
3/
10/
83,
the
registrant
indicated
that
the
methanol
soluble
activity
of
straw
contained
8
metabolites
(
each
<
0.01
to
0.02
ppm)
and
the
foliage
contained
at
least
11
metabolites,
with
no
parent
compound
present.

Corn:
Metabolism
data
were
submitted
for
the
petition
for
a
temporary
tolerance
of
imazaquin
on
corn.
HED
determined
that
for
the
purposes
of
a
temporary
tolerance
on
corn,
the
nature
of
residue
in
corn
is
the
parent
compound
(
D216732,
W.
Wassell,
2/
11/
97).
A
brief
description
of
the
methodology
and
results
of
the
corn
metabolism
study
follows:

Following
a
single
preplant
incorporated
(
PPI)
or
preemergence
(
PRE)
application
of
[
14C]
imazaquin
to
field
corn
plants
at
0.5
lb
ae/
A
(
4x
the
proposed
maximum
application
rate),
the
total
radioactive
residues
(
expressed
as
imazaquin
equivalents)
were
0.045­
0.585
ppm
in/
on
forage,
0.012­
0.024
ppm
in/
on
silage,
0.018­
0.033
ppm
in/
on
fodder,
and
0.007­
0.016
ppm
in/
on
grain.
The
bulk
of
residue
characterization
and
identification
were
conducted
on
immature
forage
samples
(
15
and
30
DAT)
since
this
commodity
contained
the
highest
levels
of
radioactivity.
Following
extraction
and
HPLC
analyses,
­

79­
95%
of
TRR
in
forage
were
characterized/
identified.
The
principal
component
identified
was
the
parent
imazaquin
which
accounted
for
­

23­
34%
of
the
TRR
in
forage.
The
metabolites,
5­
hydroxy
imazaquin
(
CL
343,684)
and
quinoline­
2,3­
dicarboxylic
acid
(
CL
263,875)
were
also
qualitatively
identified
in
the
aqueous
fractions
of
corn
forage.
The
remainder
of
the
characterized
radioactivity
consisted
of
several
metabolite
regions
(
designated
as
Metabolites
A
through
I)
mostly
comprising
<
10%
of
the
TRR,
except
for
Metabolite
F
which
comprised
­

21%
of
TRR
(
0.125
ppm)
in
15­
DAT
PPI
forage.
Further
analytical
work
to
isolate
and
identify
the
polar
Metabolite
F
was
not
successful,
but
HPLC
analysis
of
the
isolated
fraction
characterized
the
metabolite
to
be
multi­
component
in
nature.

The
proposed
metabolic
pathway
of
imazaquin
applied
to
corn
is
as
follows:
(
i)
direct
conjugation
of
the
parent
chemical;
(
ii)
hydroxylation
of
the
parent
chemical
to
its
5­
hydroxy
metabolite
(
CL
343,684)
followed
by
conjugation;
and
(
iii)
degradation
of
the
imidazoline
ring
system
to
quinoline­
2,3­
dicarboxylic
acid
(
CL
263,875)
followed
by
conjugation.
Plant
residues,
although
substantive
in
the
early
growth
stages,
are
comprised
of
a
variety
of
metabolites
which
decline
in
content
to
<
0.01
ppm
in
mature
field
corn
commodities.

3.2.2
Description
of
Livestock
Metabolism
The
available
ruminant
metabolism
study
indicates
that
the
total
radioactive
residues
were
nondetectable
in
milk,
liver,
kidney,
muscle
and
fat
of
lactating
goats
following
oral
administration
Page
17
of
68
of
[
14C]
imazaquin
at
0.25
and
0.75
ppm
for
seven
consecutive
days;
the
limits
of
detection
were
<
0.01
ppm
for
milk
and
<
0.05
ppm
for
tissues.
The
poultry
metabolism
study
indicates
that
the
total
radioactive
residues
were
also
nondetectable
(<
0.05
ppm)
in
egg
white,
egg
yolk,
muscle,
liver,
kidney,
skin
and
fat
of
laying
hens
following
oral
administration
of
[
14C]
imazaquin
at
0.25
and
0.75
for
seven
consecutive
days.

3.2.3
Description
of
Rotational
Crop
Metabolism,
including
identification
of
major
metabolites
and
specific
routes
of
biotransformation
A
confined
rotational
crop
residue
study
was
conducted
using
phenyl
14C­
labeled
imazaquin
mixed
with
quinoline
13C­
labeled.
The
chemical,
formulated
as
the
ammonium
salt
of
imazaquin,
was
applied
to
soil
at
the
rate
of
0.19
lbs
ai/
A
and
incorporated
2
inches.
Soybeans
were
planted
and
grown
to
maturity,
at
about
4.5
months.
Winter
wheat
was
planted
3
months
after
treatment
and
spring
wheat
and
field
corn
were
planted
8.5
months
after
treatment.
Carrots
and
lettuce
were
also
planted
9.5
months
after
treatment.
TRRs
ranged
from
<
0.01
ppm
to
0.07
ppm.
The
maximum
TRR
observed
in
the
study
was
in
winter
wheat
straw
(
0.07
ppm).
Sixty
percent
of
the
wheat
straw
residue
was
extractable.
The
extractable
residue
was
separated
on
HPLC
into
7
­
9
unknown
compounds,
each
at
a
level
below
0.01
ppm.
No
residues
were
identified
in
the
rotational
crop
study.

3.3
Environmental
Degradation
Imazaquin
is
an
imidazole
compound
that
is
highly
mobile
(
median
K
oc
=
17.5)
and
non­
volatile
(
vapor
pressure
<
2E­
8
torr).
In
terrestrial
environments
it
is
persistent
(
aerobic
t
1/
2
=
7
months,
anaerobic
t
1/
2
=
stable).
In
aquatic
environments,
imazaquin
is
stable
to
hydrolysis
at
all
pH
levels.
No
aquatic
metabolism
data
are
available
for
imazaquin.

The
most
significant
degradation
occurred
in
the
aqueous
photolysis
study,
in
which
the
half­
life
was
<
1
day
at
all
pHs.
The
major
photolytic
degradates,
in
addition
to
CO
2
,
were
3­
quinolinecarboxylic
acid
(
14%
of
the
applied
amount),
2,3­
quinolinecarboxylic
acid
imide
(
21%),
2,3­
dihydro­
3­
imino­
1H­
pyrrolo­[
3,4b]
quinolin­
1­
one
(
12.6%),
and
2,3­
quinolinedicarboxylic
acid
(>
30%).
There
were
18
unidentified
minor
(<
10%)
degradates.

No
major
degradates
were
identified
in
the
aerobic
soil
metabolism
study.
The
primary
degradate
resulting
from
aerobic
soil
metabolism,
in
addition
to
CO
2
,
was
(
2­[(
1­
carbamoyl­
1,2­
dimethylpropyl
carbamoyl]­
3­
quinolinecarboxylic
acid;
however,
this
compound
reached
a
maximum
of
only
7.6%
of
the
applied
amount.
Up
to
six
other
minor,
unidentified
compounds
accounted
for
11
to
14%
of
the
applied
amount.
Page
18
of
68
N
N
H
N
OH
O
O
CH
3
CH(
CH
3
)
2
N
N
H
N
OH
O
O
CH
3
CH(
CH
3
)
2
OH
N
OH
O
O
OH
3.4
Tabular
Summary
of
Metabolites
and
Degradates
Table
3.4.
Tabular
Summary
of
Metabolites
and
Degradates
Chemical
Name
Commodity
Percent
TRR
(
PPM)

Structure
Matrices
­
Major
Residue
(>
10%
TRR)
Matrices
­
Minor
Residue
(<
10%
TRR)

Imazaquin
(
CL
252,214)

2­[
4,5­
dihydro­
4­
methyl­
4­(
1­
methylethyl)­
5­
oxo­
1H­
imidazol­
2­
yl]­
3­
quinolinecarboxylic
acid
soybean
­
­

corn
(
immature
forage)
34
­

Rotational
Crops
­
­

Ruminant
­
­

Poultry
­
­

Rat
94
(
urine)
­

Water
­

5­
Hydroxy
imazaquin
(
CL
343,684)

2­[
4,5­
dihydro­
4­
methyl­
4­(
1­
methylethyl)­
5­
oxo­
1H­
imidazol­
2­
yl]­
5­
hydroxy­
3­
quinolinecarboxylic
acid
soybean
­
­

corn
(
immature
forage)
qualitative
only
qualitative
only
Rotational
Crops
­
­

Ruminant
­
­

Poultry
­
­

Rat
­
­

Water
­
­

(
CL
263,875)

2,3­
quinoline
dicarboxylic
acid
soybean
­
­

corn
(
immature
forage)
qualitative
only
qualitative
only
Rotational
Crops
­
­

Ruminant
­
­

Poultry
­
­

Rat
­
­

Water
>
30*
­
Table
3.4.
Tabular
Summary
of
Metabolites
and
Degradates
Chemical
Name
Commodity
Percent
TRR
(
PPM)

Structure
Matrices
­
Major
Residue
(>
10%
TRR)
Matrices
­
Minor
Residue
(<
10%
TRR)

Page
19
of
68
N
O
OH
N
NH
NH
O
N
NH
O
O
(
CL
75,
947)

3­
quinolinecarboxylic
acid
soybean
­
­

corn
­
­

Rotational
Crops
­
­

Ruminant
­
­

Poultry
­
­

Rat
­
­

Water
14*
­

2,3­
dihydro­
3­
imino­
1H­
pyrrolo­
[
3,4b]
quinolin­
1­
one
soybean
­
­

corn
­
­

Rotational
Crops
­
­

Ruminant
­
­

Poultry
­
­

Rat
­
­

Water
13*
­

2,3­
quinolinecarboxylic
acid
imide
soybean
­
­

corn
­
­

Rotational
Crops
­
­

Ruminant
­
­

Poultry
­
­

Rat
­
­

Water
21*
­

*
percent
of
total
applied
(
not
%
TRR)
Soybean;
MRIDs
131563,
131546,
147012
42874001
;
0.38
lb
ai/
A
(
1.5x);
preplant,
early
post­
emergent
Corn:
MRID
43671601;
0.5
lb
ae/
A
(
4x);
preplant,
early
preemergent
Goats;
MRID
147012;
0.75
ppm;
94X
MTDB;
7
days
Hens;
MRID
147012;
0.75
ppm;
68X
MTDB;
7
days
Rotational
Crops;
MRID
147012;
wheat,
corn,
lettuce,
carrot;
0.75x,
applied
to
bare
soil;
3­
8.5
months
PBI
Page
20
of
68
3.5
Toxicity
Profile
of
Major
Metabolites
and
Degradates
Based
on
submitted
studies,
there
are
no
major
metabolites
of
imazaquin
identified
in
plants
and
animals.
The
major
degradates
that
could
potentially
be
found
in
drinking
water
include
3­
quinolinecarboxylic
acid,
2,3­
quinolinecarboxylic
acid
imide,
2,3­
dihydro­
3­
imino­
1H­
pyrrolo­
[
3,4b]
quinolin­
1­
one,
and
2,3­
quinolinedicarboxylic
acid.
Specific
toxicity
data
are
not
available
for
these
compounds;
however,
based
on
their
structural
similarity
to
the
parent,
the
risk
assessment
team
has
concluded
that
they
may
have
toxicity
similar
to
parent
imazaquin
and
should
be
included
in
the
dietary
risk
assessment.

3.6
Summary
of
Residues
for
Tolerance
Expression
and
Risk
Assessment
3.6.1
Tabular
Summary
Table
3.6.
Summary
of
Metabolites
and
Degradates
to
be
included
in
the
Risk
Assessment
and
Tolerance
Expression
Matrix
Residues
included
in
Risk
Assessment
Residues
included
in
Tolerance
Expression
Plants
Primary
Crop
imazaquin,
per
se
imazaquin,
per
se
Rotational
Crop
imazaquin,
per
se
imazaquin,
per
se
Livestock1
Ruminant
NA
NA
Poultry
NA
NA
Drinking
Water
from
Surface
Water
Sources
imazaquin
3­
quinolinecarboxylic
acid
2,3­
quinolinecarboxylic
acid
imide
2,3­
dihydro­
3­
imino­
1Hpyrrolo
3,4b]
quinolin­
1­
one
2,3­
quinolinedicarboxylic
acid
NA
Drinking
Water
from
Ground
Water
Sources
imazaquin,
per
se
NA
1
HED
has
determined
that
40
CFR
§
180.6(
a)(
3)
is
applicable
to
imazaquin;
there
is
no
reasonable
expectation
of
finite
residues
in
ruminants
or
poultry.
Page
21
of
68
3.6.2
Rationale
for
Inclusion
of
Metabolites
and
Degradates
The
nature
of
the
residue
in
plants
is
adequately
understood
for
the
use
of
imazaquin
on
soybeans.
Based
on
the
trace
levels
of
radioactivity
found
in
the
soybean
seed
from
an
exaggerated
application
rate,
the
apparent
extensive
degradation
of
imazaquin
into
plant
constituents,
and
the
livestock
grazing/
feeding
prohibition
of
forage,
straw
and
hay
on
current
labels,
the
residue
of
concern
for
both
risk
assessment
and
tolerance
enforcement
is
imazaquin,
per
se.

Tolerances
for
imazaquin
residues
in
livestock
commodities
need
not
be
established
as
a
result
of
the
current
label
use
on
soybeans,
based
on
the
absence
of
detectable
residues
in
eggs,
milk,
and
livestock
tissues
from
the
available
animal
metabolism
studies
and
the
absence
of
detectable
residues
in
the
submitted
magnitude
of
residue
studies
in
livestock
feedstuffs.
Similarly,
since
there
is
no
expectation
of
finite
residues
in
livestock
commodities,
they
need
not
be
included
in
the
dietary
risk
assessment.

The
major
degradates
that
could
potentially
be
found
in
drinking
water
from
surface
water
sources
include
3­
quinolinecarboxylic
acid,
2,3­
quinolinecarboxylic
acid
imide,
2,3­
dihydro­
3­
imino­
1H­
pyrrolo­[
3,4b]
quinolin­
1­
one,
and
2,3­
quinolinedicarboxylic
acid.
Specific
toxicity
data
are
not
available
for
these
compounds;
however,
based
on
their
structural
similarity
to
the
parent,
the
risk
assessment
team
has
concluded
that
they
may
have
toxicity
similar
to
parent
imazaquin
and
should,
therefore,
be
included
in
the
dietary
risk
assessment.
These
photolytic
degradates
are
not
expected
to
form
in
drinking
water
from
ground
water
sources;
therefore,
the
residue
of
concern
in
drinking
water
from
ground
water
sources
is
imazaquin,
per
se.

4.0
Hazard
Characterization/
Assessment
4.1
Hazard
Characterization
4.1.1.
Database
Summary
4.1.1.1.
Studies
available
and
considered
A
complete
battery
of
acceptable
toxicity
studies
was
available
and
considered.
Acute
studies
included
oral
and
inhalation
toxicity
studies
in
the
rat;
dermal
toxicity,
primary
eye
and
dermal
irritation
studies
in
rabbits;
and
a
dermal
sensitization
study
with
guinea
pigs.
Subchronic
dermal
toxicity
was
assessed
in
a
21­
day
dermal
study
in
rabbits.
Subchronic
and
chronic
feeding
studies
included
rat
90­
day
and
chronic
toxicity/
carcinogenicity
studies,
a
dog
chronic
study
and
a
mouse
carcinogenicity
study.
Developmental
toxicity
was
assessed
in
both
rats
and
rabbits,
and
reproductive
and
offspring
toxicity
were
assessed
in
a
rat
reproductive
study.
The
absorption,
distribution
and
excretion
of
imazaquin
was
successfully
assessed
in
a
rat
metabolism
study.
Several
genetic
toxicity
studies
were
available
to
demonstrate
that
imazaquin
was
not
mutagenic.
A
single
special
study
to
assess
for
possible
thyroid
function
effects
of
imazaquin
was
also
Page
22
of
68
available.
No
special
neurotoxicity
studies
were
available,
and
these
are
not
considered
necessary
to
assess
the
hazard
of
imazaquin
to
humans.

4.1.1.2.
Mode
of
action,
metabolism
and
toxicokinetic
data
Mode
of
Action.
The
mode
of
action
of
imazaquin
in
plants
involves
the
inhibition
of
the
synthesis
of
specific
amino
acids
(
valine,
leucine
and
isoleucine)
necessary
for
plant
growth.
Valine,
leucine
and
isoleucine
are
essential
amino
acids
in
humans,
meaning
that
they
are
not
synthesized
in
the
mammalian
body
and
must
be
obtained
from
food
sources.
Since
they
are
not
synthesized
in
mammals,
the
mechanism
of
herbicidal
action
of
imazaquin
is
not
operative
in
mammals
and
not
applicable
to
humans.

Metabolism.
The
toxicokinetic
data
for
imazaquin
indicate
that
it
is
rapidly
absorbed
and
excreted
by
the
rat
following
oral
administration.
In
the
rat
metabolism
study,
essentially
all
(
102%)
of
the
administered
radioactivity
was
recovered
within
48
hours
of
treatment.
The
majority
(
94%)
was
recovered
in
the
urine,
with
4%
recovered
in
the
feces
and
4%
recovered
in
the
cage
wash.
Twenty­
four
hours
after
treatment,
residual
radioactivity
was
detected
in
the
liver
(
0.025
ppm)
and
kidney
(
0.17
ppm);
however,
by
48
hours,
the
concentration
in
all
tissues
was
at
or
below
the
limit
of
detection
(
0.01
ppm).
Analysis
of
urine
collected
24
and
48
hours
after
treatment
showed
that
99.7%
of
the
recovered
radioactivity
was
unchanged
parent
compound,
indicating
that
imazaquin
is
poorly
metabolized
in
the
rat.

4.1.1.3.
Sufficiency
of
studies/
data
The
toxicity
studies
with
imazaquin
are
considered
to
be
sufficient
to
evaluate
the
various
parameters
for
which
they
were
designed.

4.1.2.
Toxicological
effects
Imazaquin
demonstrated
low
acute
toxicity
in
oral
and
inhalation
studies
in
rats
with
LD
50
and
LC
50
values
of
>
5000
mg/
kg
and
>
5.5
mg/
L,
respectively
.
It
also
demonstrated
low
toxicity
in
rabbits
via
the
dermal
route
with
a
dermal
LD
50
of
>
2000
mg/
kg.
In
primary
dermal
and
eye
irritation
studies
in
rabbits,
the
chemical
was
only
mildly
irritating
and
non­
irritating,
respectively.
Imazaquin
was
not
a
dermal
sensitizer
in
guinea
pigs.

Overall,
imazaquin
appears
to
demonstrate
subchronic
and
chronic
toxicity
only
at
higher
doses,
with
few
clinical
signs
identified
in
rats,
mice,
dogs
or
rabbits.
Toxicity
was
similar
in
both
male
and
female
test
animals.
The
dog
was
the
most
sensitive
species
to
exposure
to
imazaquin.

The
most
common
clinical
sign
observed
in
the
chronic
studies
was
decreased
body
weight
in
the
dog
and
mouse.
In
the
chronic
dog
study,
weight
loss,
slight
anemia
indicated
by
changes
in
hematology
parameters,
changes
to
clinical
chemistry
and
skeletal
muscle
myopathy
at
necropsy
in
both
sexes
were
noted
at
the
LOAEL
of
125
mg/
kg/
day
(
5000
ppm).
Decreases
in
body
weight
in
Page
23
of
68
male
and
female
mice
in
the
carcinogenicity
study
are
the
basis
for
the
LOAEL
of
600
mg/
kg/
day.
In
the
rat
combined
chronic
toxicity/
carcinogenicity
study,
the
LOAEL
was
not
established
as
there
were
no
effects
observed
at
the
highest
dose
administered
(
10,000
ppm
or
500
mg/
kg/
day).

No
indications
of
systemic
toxicity
were
noted
in
the
21­
day
dermal
toxicity
study
in
rabbits,
and
the
NOAEL
was
established
as
1000
mg/
kg/
day
(
the
highest
dose
tested).
The
only
dermal
lesion
was
observed
in
one
high­
dose
rabbit
with
slight
dermal
erythema
at
the
treated
site
for
a
limited
period
of
time.

In
prenatal
developmental
toxicity
studies,
maternal
toxicity
in
the
rat
was
indicated
by
two
deaths
and
adverse
clinical
signs
observed
when
imazaquin
was
administered
by
gavage
at
2000
mg/
kg/
day.
These
clinical
signs
included
salivation,
stained
genital
area,
ocular
discharge,
rough
haircoat
and
lethargy.
In
rat
fetuses,
treatment­
related
effects
on
body
weight
and
reduced
ossification
were
observed
at
2000
mg/
kg/
day.
Maternal
toxicity
in
rabbits
was
demonstrated
by
decreased
weight
gain
at
500
mg/
kg/
day
(
the
highest
dose
tested).
There
were
no
treatmentrelated
development
effects
in
rabbit
fetuses
at
the
500
mg/
kg/
day
dose.

Imazaquin
did
not
adversely
affect
reproductive
parameters
or
cause
systemic
toxicity
or
developmental
effects
in
rats
over
three
generations,
and
the
NOAEL
for
both
parental
and
offspring
toxicity
was
$
10,000
ppm
[
870­
938
mg/
kg/
day
in
males
and
947­
1051
mg/
kg/
day
in
females].

Mice
were
dosed
up
to
600
mg/
kg/
day
(
4000
ppm)
for
18
months,
and
rats
were
fed
up
to
500
mg/
kg/
day
(
10,000
ppm)
for
2
years
without
any
evidence
of
a
treatment­
related
increased
incidence
of
tumors.
Imazaquin
was
non­
mutagenic
in
the
Ames
test,
and
negative
responses
were
also
demonstrated
in
the
in
vitro
cell
transformation
assay,
a
cytogenetics
study
with
HGPRT
in
Chinese
hamster
cells
and
an
unscheduled
DNA
synthesis
assay.

Evidence
of
specific
neurotoxicity
or
immunotoxicity
was
not
observed
in
any
study.

A
special
non­
guideline
study
to
assess
thyroid
function
in
male
rats
fed
imazaquin
for
up
to
92
days
at
concentrations
of
100
or
5000
ppm
(
4.98
or
254.4
mg/
kg/
day,
respectively)
demonstrated
an
approximately
2­
fold
increase
in
adjusted
TSH
(
thyroid
stimulating
hormone)
with
a
corresponding
decrease
in
total
serum
T
4
at
the
highest
dose
tested
(
254
mg/
kg/
day).
Minimal
to
moderate
thyroid
follicular
cell
hypertrophy
was
also
observed
only
at
the
highest
dose.
Thus,
imazaquin,
at
higher
doses,
may
have
some
endocrine
effects;
however,
these
may
be
due
to
a
secondary
effect
of
altered
hepatic
metabolizing
capacity.
Page
24
of
68
4.1.3.
Dose
response
The
most
common
effect
observed
was
decreased
body
weight,
which
was
observed
in
the
dog
at
125
mg/
kg/
day,
in
the
mouse
at
600
mg/
kg/
day
and
the
rabbit
at
500
mg/
kg/
day.
These
doses
were
the
highest
doses
tested
in
each
species,
so
that
dose
response
information
was
not
further
investigated.
In
addition
to
the
body
weight
effect,
adverse
signs
were
observed
in
the
chronic
dog
feeding
study,
but
only
at
the
highest
test
dose.
These
included
a
slight
anemia,
changes
in
clinical
chemistry
parameters
and
skeletal
muscle
myopathy.
No
effects
on
body
weight
were
observed
at
the
highest
doses
tested
in
the
rat
subchronic
and
chronic
studies,
although
decreased
body
weight
was
noted
at
the
high
dose
in
the
special
study
for
assessment
of
thyroid
function.

4.1.4.
FQPA
The
database
is
considered
adequate
to
characterize
any
potential
pre­
and/
or
post­
natal
risk
to
infants
and
children.
Additional
studies
are
not
required.
Neither
the
rat
nor
rabbit
prenatal
developmental
toxicity
studies
nor
the
rat
multi­
generation
reproduction
study
demonstrated
increased
sensitivity
of
the
fetuses
or
the
offspring
to
imazaquin.
Therefore,
since
there
is
no
increased
risk
to
infants
and
children
and
no
residual
uncertainty,
the
special
FQPA
Safety
Factor
may
be
reduced
to
1X.

4.1.5.
Acute
Toxicity
Imazaquin's
acute
toxicity
profile
is
presented
below
in
Table
4.1.5.

Table
4.1.5
Acute
Toxicity
Profile
­
Imazaquin
Guideline
No.
Study
Type
MRID(
s)
Results
Toxicity
Category
870.1100
Acute
oral
[
rat]
00132576
LD50
=
>
5000
mg/
kg
IV
870.1200
Acute
dermal
[
rabbit]
00132576
LD50
>
2000
mg/
kg
III
870.1300
Acute
inhalation
[
rat]
00146199
>
5.5
mg/
L
(
4
hours)
III
870.2400
Acute
eye
irritation
[
rabbit]
00132576
Non­
irritating
IV
870.2500
Acute
dermal
irritation
[
rabbit]
00132576
Mildly
irritating
IV
870.2600
Skin
sensitization
[
guinea
pig]
00146200
Negative
­
not
a
sensitizer
N/
A
Page
25
of
68
4.1.6.
Sub­
chronic/
Chronic
and
Other
Toxicity
Table
4.1.6
Subchronic,
Chronic
and
Other
Toxicity
Profile
­
Imazaquin
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
870.3100
90­
Day
oral
toxicity
(
rat)
00131553
(
1983)
Acceptable/
guideline
M&
F:
0,
20,
80,
400
or
800
mg/
kg/
day
0,
250,
1000,
5000
or
10,000
ppm
NOAEL:
800
mg/
kg/
day
LOAEL:
not
established
870.3150
90­
Day
oral
toxicity
No
study.
See
chronic
dog
study
below.

870.3200
21/
28­
Day
dermal
toxicity
(
rabbit)
00146204
(
1985)
Acceptable/
guideline
M&
F:
0,
250,
500
or
1000
mg/
kg/
day
Systemic
NOAEL
=
1000
mg/
kg/
day
LOAEL
=
not
established
Dermal
NOAEL
=
1000
mg/
kg/
day
LOAEL
=
Not
established
(
no
effects
at
highest
dose
tested)

870.3250
90­
Day
dermal
toxicity
No
study
and
not
required.

870.3465
90­
Day
inhalation
toxicity
(
species)
No
study
and
not
required.

870.3700a
Prenatal
developmental
(
rat)
00131552
(
1983)
Acceptable/
guideline
0,
250,
500
or
2000
mg/
kg/
day
Maternal
NOAEL
=
500
mg/
kg/
day
LOAEL
=
2000
mg/
kg/
day,
based
on
salivation,
alopecia,
lethargy,
flaccidity
and
2/
25
deaths
Developmental
NOAEL
=
500
mg/
kg/
day
LOAEL
=
2000
mg/
kg/
day,
based
on
sl.
decrease
in
fetal
weight
and
reduced
ossification.

870.3700b
Prenatal
developmental
in
(
rabbit)
00147011
(
1984)
Acceptable/
guideline
0,
100,
250,
or
500
mg/
kg/
day
Maternal
NOAEL
=
250
mg/
kg/
day
LOAEL
=
500
mg/
kg/
day
based
on
decreased
weight
gain.
Developmental
NOAEL
$
500
mg/
kg/
day
(
no
effects
seen
at
highest
dose)
LOAEL
=
not
identified
Table
4.1.6
Subchronic,
Chronic
and
Other
Toxicity
Profile
­
Imazaquin
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
26
of
68
870.3800
Reproduction
and
fertility
effects
(
rat)
00147016
(
1985)
Acceptable/
guideline
0,
92­
97,
431­
483
or
870­
938
mg/
kg/
day
(
M)
0,
99­
108,
498­
525
or
947­
1051
mg/
kg/
day
(
F)
0,
1000,
5000
or
10,000
ppm
(
M
and
F)
Parental/
Systemic
NOAEL$
870­
938
mg/
kg/
day
(
M)

$
947­
1051
mg/
kg/
day
(
F)
LOAEL
=
not
identified
Reproductive
NOAEL
$
870­
938
mg/
kg/
day
(
M)

$
947­
1051
mg/
kg/
day
(
F)
LOAEL
=
not
identified
Offspring
NOAEL
$
870­
938
mg/
kg/
day
(
M)

$
947­
1051
mg/
kg/
day
(
F)
LOAEL
=
not
identified
870.4100b
Chronic
toxicity
(
dog)
00138972
(
1984)
Acceptable/
guideline
M&
F:
0,
5,
25
or
125
mg/
kg/
day
0,
200,
1000
or
5000
ppm
NOAEL
=
25
mg/
kg/
day
LOAEL
=
125
mg/
kg/
day,
based
on
decreased
body
weight
gain,
skeletal
muscle
myopathy,
elevated
clinical
chemistry
values
(
ALT,
AST,
LDH,
CPK)
and
decreased
hematology
values
(
RBC,
Hgb,
Hct,
MCV
and
MCH)

870.4200
Carcinogenicity
(
rat)
See
combined
toxicity/
carcinogenicity
study
in
rats
below
870.4300
Carcinogenicity
(
mouse)
00146206
(
1985)
Acceptable/
guideline
M&
F:
0,
38,
150
or
600
mg/
kg/
day
(
estimated
by
calculation)
0,
250,
1000
or
4000
ppm
NOAEL
=
150
mg/
kg/
day
(
MF)
LOAEL
=
600
mg/
kg/
day,
based
on
decreased
body
weight
gain
in
females
and
males
no
evidence
of
carcinogenicity
in
mice
870.4300
Combined
chronic
toxicity/
carcinoge
nicity
(
rat)
00146205
(
1985)
Acceptable/
guideline
M&
F:
0,
50,
250
or
500
mg/
kg/
day
0,
1000,
5000
or
10,000
ppm
NOAEL
$
500
mg/
kg/
day
(
no
effects
at
highest
dose
tested).
LOAEL
=
not
identified
no
evidence
of
carcinogenicity
in
rats
Gene
Mutation
870.5100
(
Ames
test)
00131549
(
1982)
Minimum
Non­
mutagenic
Cytogenetics
870.5300
(
in­
vitro
cell
transformation)
00147018
(
1984)
Acceptable
Negative
Table
4.1.6
Subchronic,
Chronic
and
Other
Toxicity
Profile
­
Imazaquin
Guideline
No./
Study
Type
MRID
No.
(
year)/
Classification
/
Doses
Results
Page
27
of
68
Cytogenetics
870.5375
(
HGPRT
in
Chinese
hamster)
00147017
(
1985)
Acceptable
Negative
Other
mechanism
870.5550
(
unscheduled
DNA
synthesis)
00147019
(
1984)
Acceptable/
guideline
Negative
870.6200a
Acute
neurotoxicity
screening
battery
No
study
and
not
required.

870.6200b
Subchronic
neurotoxicity
screening
battery
No
study
and
not
required.

870.6300
Developmental
neurotoxicity
No
study
and
not
required.

870.7485
Metabolism
and
pharmacokinetics
(
rat)
00131550
(
1983)
Acceptable/
Nonguideline
0
or
12
mg/
kg
94%
recovered
in
urine
and
3.94%
in
the
feces
with
3.75%
recovered
in
the
cage
washings.
Total
recovery
­
102%.
Only
parent
(
99.7%)
was
detected
in
the
urine.

870.7600
Dermal
penetration
No
study
and
not
required.

Special
studies
90­
day
thyroid
function
(
rats)
42054601­
(
1991)
Acceptable/
Nonguideline
0,
100
and
5000
ppm
or
4.98
and
245.4
mg/
kg/
day.
NOAEL
=
4.98
mg/
kg/
day
LOAEL
=
245.4
mg/
kg/
day,
based
on
slight
decrease
in
body
weight
with
a
20%
decrease
in
body
weight
gain
and
increase
in
TSH
(
up
to
2
fold)
accompanied
by
a
decrease
in
serum
total
T4
and
a
slight
decrease
in
serum
T3.

4.2
FQPA
Hazard
Considerations
4.2.1
Adequacy
of
the
Toxicity
Data
Base
Page
28
of
68
Data
are
adequate
for
evaluation
of
effects
resulting
from
in
utero
and
post­
natal
exposure
to
imazaquin.
Relevant
studies
include
both
rat
and
rabbit
prenatal
developmental
toxicity
studies
and
the
rat
multi­
generation
reproduction
study.

4.2.2
Evidence
of
Neurotoxicity
No
behavioral
alterations
or
evidence
of
neuropathological
effects
were
observed
in
any
of
the
available
guideline
studies
with
rats,
rabbits
or
dogs.
There
are
no
series
870.6200
(
acute
or
subchronic)
neurotoxicity
screen
studies
or
an
870.6300
developmental
neurotoxicity
screen
study,
and
these
studies
are
not
being
required,
since
there
is
no
evidence
that
imazaquin
is
neurotoxic
and
other
systemic
toxicity
occurs
only
at
higher
doses.
The
presence
of
salivation
in
the
dams
in
the
rat
prenatal
developmental
toxicity
study
was
not
considered
a
primary
neurotoxic
response.

4.2.3
Developmental
Toxicity
Studies
Developmental
Toxicity
in
Rats
EXECUTIVE
SUMMARY:
In
a
prenatal
developmental
toxicity
study
(
1983,
MRID
00131552),
25
presumed
pregnant
Crl:
CD
®
(
SD)
BR
rats
per
group
were
administered
0,
250,
500,
or
2000
mg/
kg/
day
of
AC
252,214
(
89.4%
a.
i.;
Lot
No.
AC­
4325­
96
in
corn
oil)
by
gavage
on
gestation
days
(
GD)
6­
15,
inclusive.
On
GD
20,
the
dams
were
sacrificed
and
cesarian
sectioned.
All
fetuses
were
weighed,
sexed
and
examined
for
external
malformations/
variations.
Approximately
one­
third
of
the
fetuses
were
examined
for
visceral
malformations/
variations
by
the
Wilson
technique.
The
remaining
fetuses
were
processed
for
skeletal
examination.

Maternal
Toxicity:
Two
animals
in
the
high­
dose
group
were
found
dead,
one
each
on
GDs
16
and
17.
Clinical
signs
in
these
animals
included
salivation
after
dosing,
stained
genital
area
and
fur,
rough
coat,
ocular
discharge,
and
lethargy;
no
abnormalities
were
found
at
necropsy.
Salivation
(
dams
affected/
mean
severity
score)
after
dosing
was
observed
in
all
treated
groups
with
low
(
18/
1.33)­,
mid
(
14/
1.44)­,
and
high
(
25/
1.84)­
dose
groups,
respectively.
Urogenital
staining
was
seen
in
8
high­
dose
animals.
Maternal
body
weight
was
similar
between
the
treated
and
control
groups
throughout
the
study.
Maternal
food
consumption
was
not
measured.
Gross
necropsy
was
unremarkable.
The
maternal
toxicity
LOAEL
for
AC
252,214
is
2000
mg/
kg/
day
based
on
death
and
clinical
signs
of
toxicity.
The
NOAEL
is
500
mg/
kg/
day.
Note:
The
salivation
was
not
considered
a
specific
neurotoxic
response,
and
there
was
no
dose
response
between
the
low­
and
mid­
dose
groups;
therefore,
this
effect
was
not
included
in
the
LOAEL.

Developmental
Toxicity:
At
cesarean
section,
the
number
of
corpora
lutea,
number
of
implantations
per
dam,
implantation
efficiency,
live
fetuses
per
litter,
and
fetal
sex
ratios
were
similar
between
the
treated
and
control
groups.
Pregnancy
rate
was
84%
for
the
high­
dose
group
and
88­
92%
for
the
control,
low­,
and
mid­
dose
groups.
Mean
fetal
body
weight
at
the
high
dose
Page
29
of
68
was
significantly
less
than
that
of
the
controls.
No
dose­
or
treatment­
related
external
or
visceral
malformations/
variations
were
observed.
Reduced
ossification
of
fetuses
in
the
high­
dose
group
was
evident
as
indicated
by
a
significantly
greater
number
of
litters
containing
fetuses
with
reduced
or
not
ossified
skull,
hyoid,
sternebrae,
and
metacarpals.
The
developmental
toxicity
LOAEL
for
AC
252,214
in
rats
is
2000
mg/
kg/
day,
based
on
decreased
fetal
body
weight
and
reduced
ossification.
The
NOAEL
is
500
mg/
kg/
day.

This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
[
OPPTS
870.3700
(
83­
3a)]
in
rats.
This
study
was
conducted
prior
to
implementation
of
current
guidelines.

Developmental
Toxicity
in
Rabbits
EXECUTIVE
SUMMARY:
In
a
developmental
toxicity
study
(
1984,
MRID
00147011),
19
inseminated
New
Zealand
white
rabbits
per
group
were
administered
0,
100,
250,
or
500
mg/
kg/
day
of
AC
252,214
(
89.4%
a.
i.;
Lot
No.
AC­
4325­
96)
by
gavage
on
gestation
days
(
GD)
6­
18,
inclusive.
A
0.5%
aqueous
methylcellulose
solution
was
used
as
the
vehicle.
On
GD
29,
all
surviving
does
were
sacrificed
and
subjected
to
gross
examination.
All
fetuses
were
weighed
and
examined
for
external,
visceral,
and
skeletal
malformations/
variations.
The
brain
was
examined
by
a
mid­
coronal
slice.

Maternal
toxicity:
One
high­
dose
animal
was
found
dead
on
GD
11;
necropsy
findings
of
hemorrhage
and
congestion
in
the
internal
organs,
hyperemia
of
the
kidney,
and
accentuation
of
the
lobular
pattern
of
the
liver
were
inconclusive
of
a
treatment­
related
effect.
Other
deaths
and
one
abortion
by
several
treated
and
control
animals
were
incidental
to
treatment.
No
clinical
signs
of
toxicity
were
observed
in
any
doe.
Absolute
maternal
body
weight
was
similar
between
the
treated
and
control
groups
throughout
the
study.
Body
weight
gain
by
the
high­
dose
group
was
significantly
reduced
(
p
#
0.05;
13%)
during
the
treatment
interval.
The
most
pronounced
effect
on
body
weight
was
during
GD
6­
12
when
the
high­
dose
group
had
a
weight
loss
(­
25
g)
compared
to
a
weight
gain
by
the
controls
(+
50
g).
Maternal
food
consumption
was
not
measured.
Gross
necropsy
was
unremarkable.
The
maternal
toxicity
LOAEL
is
500
mg/
kg/
day
based
on
decreased
body
weight
gain.
The
maternal
toxicity
NOAEL
is
250
mg/
kg/
day.

Developmental
toxicity:
At
cesarean
section,
no
treatment­
related
effects
were
seen
for
the
number
of
corpora
lutea,
number
of
implantations
and
resorptions
per
dam,
post
implantation
loss,
number
of
live
fetuses
per
litter,
and
fetal
sex
ratio.
The
number
of
fetuses(
litters)
examined
in
the
control,
low­,
mid­,
and
high­
dose
groups
was
85(
14),
66(
14),
66(
12),
71(
13),
respectively.
Mean
fetal
body
weight
was
similar
between
the
treated
and
control
groups.
No
dose­
or
treatment­
related
external,
visceral,
or
skeletal
malformations/
variations
were
observed
in
any
fetus.
The
developmental
toxicity
LOAEL
in
rabbits
is
not
identified
and
the
developmental
toxicity
NOAEL
is
$
500
mg/
kg/
day.
Page
30
of
68
This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
guideline
requirement
for
a
developmental
toxicity
study
[
OPPTS
870.3700
(
83­
3b)]
in
rabbits.
This
study
was
conducted
prior
to
implementation
of
current
guidelines.

4.2.4
Reproductive
Toxicity
Study
EXECUTIVE
SUMMARY:
In
a
three­
generation
reproduction
study
(
1985,
MRID
00147016),
AC
252,214
(
87.9%
a.
i.;
Lot
No.
AC
4325­
23)
was
administered
in
the
diet
to
12
male
and
24
female
CD
rats
per
group
at
concentrations
of
0,
1000,
5000,
or
10,000
ppm.
The
premating
interval
for
the
F
0
parental
animals
was
69
days.
Each
parental
generation
was
mated
for
the
first
time
at
approximately
100
days
old.
Two
litters
were
produced
in
each
generation.
Doses
for
the
parental
animals
were
0,
92.1­
97.2,
430.7­
483.4,
and
869.5­
938.1
mg/
kg/
day,
respectively,
for
males
and
0,
99.1­
107.5,
497.5­
525.4,
and
947.3­
1050.9
mg/
kg/
day,
respectively,
for
females.

Parental
Systemic
Toxicity:
No
treatment­
related
deaths
or
clinical
signs
of
toxicity
occurred
during
the
study.
Premating
body
weight,
body
weight
gain
and
food
consumption
by
adult
animals
of
all
generations
were
not
affected
by
treatment.
Differences
from
control
values
were
sporadic,
not
dose­
related
and
not
consistent
over
time.
No
treatment­
related
gross
lesions
were
observed
at
necropsy.
The
parental
systemic
toxicity
LOAEL
for
AC
252,214
in
rats
is
not
identified.
The
NOAEL
is
$
10,000
ppm
(
869.5­
938.1
and
947.3­
1050.9
mg/
kg/
day
for
males
and
females,
respectively).

Reproductive
and
Developmental
Toxicity:
Mating
and
fertility
indices
were
not
affected
by
treatment
of
any
generation
during
production
of
both
litters.
Estrous
cycles
and
sperm
parameters
were
not
evaluated;
number
of
days
to
mating,
gestation
length,
and
gestation
index
were
not
given.
The
reproductive
toxicity
LOAEL
for
AC
252,214
in
male
and
female
rats
was
not
identified.
The
reproductive
toxicity
NOAEL
is
$
10,000
ppm
(
869.5­
938.1
and
947.3­
1050.9
mg/
kg/
day
for
males
and
females,
respectively).

No
differences
were
noted
between
the
treated
and
control
groups
of
any
generation
for
number
of
pups/
litter
or
offspring
survival
during
lactation.
Offspring
body
weight
during
lactation
was
similar
between
the
treated
and
control
groups
of
all
litters
and
generations.
The
offspring
toxicity
LOAEL
for
AC
252,214
in
rats
is
not
identified.
The
offspring
toxicity
NOAEL
is
$
10,000
ppm
(
869.5­
938.1
and
947.3­
1050.9
mg/
kg/
day
for
males
and
females,
respectively).

This
study
is
classified
as
Acceptable/
Guideline
and
satisfies
the
guideline
requirement
for
a
reproductive
toxicity
study
[
OPPTS
870.3800
(
83­
4)]
in
rats.
Although
no
systemic
or
reproductive
toxicity
was
observed
at
any
dose,
the
highest
dose
approximated
the
limit
dose
of
1000
mg/
kg/
day.
This
study
was
conducted
prior
to
the
implementation
of
the
current
guidelines.

4.2.5
Additional
Information
from
Literature
Sources
Page
31
of
68
No
additional
information
on
the
toxicity
of
imazaquin
was
identified
in
the
open
literature.

4.2.6
Pre­
and/
or
Postnatal
Toxicity
4.2.6.1
Determination
of
Susceptibility
There
is
no
indication
of
increased
susceptibility
of
fetuses
or
offspring
to
imazaquin
in
the
developmental
or
reproductive
toxicity
studies.
In
the
developmental
study
in
rats,
treatmentrelated
effects
on
body
weight
and
reduced
ossification
were
observed,
but
only
at
the
dose
where
maternal
toxicity
occurred.
No
treatment­
related
effects
on
fetuses
were
seen
in
the
rabbit
developmental
toxicity
study;
and
in
the
rat
reproductive
study,
no
toxicity
in
either
the
parents
or
offspring
was
noted
at
the
highest
dose
tested.

4.2.6.2
Degree
of
Concern
Analysis
and
Residual
Uncertainties
for
Pre
and/
or
Post­
natal
Susceptibility
There
is
no
concern
and
there
are
no
residual
uncertainties
for
pre­
and/
or
postnatal
susceptibility.

4.3
Recommendation
for
a
Developmental
Neurotoxicity
Study
4.3.1
Evidence
that
supports
requiring
a
Developmental
Neurotoxicity
study
There
is
no
evidence
that
supports
requiring
a
developmental
neurotoxicity
study
with
imazaquin.

4.3.2
Evidence
that
supports
not
requiring
a
Developmental
Neurotoxicity
study
The
available
data
on
the
toxicity
of
imazaquin
do
not
support
the
recommendation
for
a
developmental
neurotoxicity
study.
Prenatal
exposure
did
not
cause
any
obvious
nervous
system
malformations.
No
clinical
signs
suggestive
of
neurotoxicity
were
reported
in
any
of
the
chronic
studies
conducted
in
mice,
rats
and
dogs.

4.3.3
Rationale
for
the
UFDB
(
when
a
DNT
is
recommended)

Not
applicable.
A
developmental
neurotoxicity
study
is
not
recommended.

4.4
Hazard
Identification
and
Toxicity
Endpoint
Selection
4.4.1
Acute
Reference
Dose
(
aRfD)
­
Females
age
13­
49
An
endpoint
attributable
to
a
single
exposure
was
not
identified
from
the
available
database.
Page
32
of
68
4.4.2
Acute
Reference
Dose
(
aRfD)
­
General
Population
An
endpoint
attributable
to
a
single
exposure
was
not
identified
from
the
available
database.

4.4.3
Chronic
Reference
Dose
(
cRfD)

Study
Selected:
Chronic
toxicity­
dog
OPPTS:
870.4100b
MRID
No.:
00138972
EXECUTIVE
SUMMARY:
In
a
chronic
toxicity
study
(
1984,
MRID
00138972),
AC
252,214
(
Imazaquin,
87.9%
a.
i.,
Lot
No.
AC
4325­
23)
was
administered
in
the
diet
to
eight
beagle
dogs/
sex/
dose
levels
of
0
(
controls),
200,
1000
or
5000
ppm
for
one
year.
Using
a
food
factor
of
0.025,
corresponding
concentrations
were
0,
5,
25,
or
125
mg/
kg
bw/
day,
respectively.

One
high­
dose
male
dog
was
sacrificed
in
a
moribund
condition
at
week
23
because
of
decreased
appetite,
weight
loss,
and
inactivity.
Necropsy
did
not
indicate
the
cause
of
death.
Clinical
signs
including
dermal
lesions
were
observed
in
all
animals
and
did
not
appear
to
be
treatment­
related.
Several
dogs
were
diagnosed
with
Demodex
mange,
which
could
have
been
the
cause
of
the
dermal
lesions.

Mean
body
weight
was
consistently
lower
(
8­
18%)
in
the
high­
dose
males
during
the
first
20
weeks
of
the
study.
After
week
20,
the
body
weights
increased
until
they
were
similar
to
controls.
Correspondingly,
mean
body
weight
gain
was
decreased
(
25%)
in
the
first
12
weeks.
High­
dose
females
had
a
decrease
in
mean
body
weight
(
10­
15%)
throughout
the
study.
Lowand
mid­
dose
males
had
occasional
slight
weight
loss
that
was
not
consistent
throughout
the
study.
The
low­
dose
females
had
a
mean
body
weight
slightly
below
the
controls
throughout
the
study
but
the
mid­
dose
values
displayed
no
dose­
trend
and
varied
between
being
higher
and
lower
than
the
controls.
Food
consumption
in
high­
dose
males
was
decreased
(
8­
23%)
but
was
comparable
and
greater
than
controls
after
approximately
week
24.
This
value
was
decreased
due
to
the
low
amount
of
food
consumed
by
the
one
high­
dose
male
sacrificed
at
week
23.
Food
consumption
by
the
high­
dose
females
decreased
slightly
(
6­
8%)
during
weeks
4­
10
but
then
was
similar
to
that
of
controls
throughout
the
remainder
of
the
study.

High­
dose
males
and
females
had
a
statistically
significant
decrease
in
the
hematology
parameters
typically
associated
with
anemia.
Animals
had
decreases
in
the
red
blood
cell
count
(
RBCs),
hemoglobin
(
Hgb),
hematocrit
(
Hct),
mean
corpuscular
volume
(
MCV),
mean
corpuscular
hemoglobin
(
MCH)
and
an
occasional
decrease
in
mean
corpuscular
hemoglobin
concentration
(
MCHC)
at
weeks
13,
26
and
52.
The
decreases
in
these
parameters
support
a
slight,
transient
microcytic,
hypochromic
anemia
that
was
improving
by
week
52.
Increased
nucleated
red
blood
cells
(
nRBC's)
(>
2
nRBC/
100
cells
in
field)
were
observed
in
3/
8,
4/
7
and
4/
7
high­
dose
males
at
weeks
13,
26
and
52,
respectively.
Increased
nRBC's
were
observed
in
the
high­
dose
females
at
weeks
13,
26
and
52
in
2/
8,
4/
8
and
4/
8
animals,
respectively.
High­
dose
males
had
a
Page
33
of
68
statistically
significant
increase
in
the
serum
aspartate
transferase
(
AST
or
SGOT),
serum
alanine
transferase
(
AST
or
SGPT),
lactate
dehydrogenase
(
LDH)
and
creatine
phosphokinase
(
CPK)
values
at
all
time­
points.
High­
dose
females
also
were
observed
to
have
significant
or
at
least
increased
values
at
all
timepoints.
At
necropsy,
mean
liver­
to­
body
weight
ratio
was
statistically
increased
in
the
high­
dose
male
(
1.2x)
and
female
(
1.3x).
The
mean
liver
weight
and
liver­
tobrain
weight
ratios
were
increased
but
were
not
statistically
significant.
Hepatic
lesions
were
not
observed.
A
degenerative
skeletal
muscle
myopathy
was
observed
in
the
high­
dose
males
(
7/
7)
and
females
(
3/
8)
versus
none
identified
in
the
controls.
This
finding
was
characterized
by
a
loss
of
striation,
increased
eosinophils
and
the
presence
of
mononuclear
inflammatory
cells.
Bone
marrow
hypercellularity
was
observed
only
in
the
high­
dose
males
(
2/
8)
and
females
(
4/
8)
as
an
increase
in
hematopoietic
cells
in
the
bone
marrow.
This
finding
is
consistent
with
a
regenerative
anemia.
The
LOAEL
for
Imazaquin
is
5000
ppm
(
125
mg/
kg
bw/
day)
based
on
a
treatment­
related
decrease
in
body
weight;
a
slight,
microcytic,
hypochromic
anemia;
skeletal
muscle
myopathy
and
clinical
chemistry
changes.
The
NOAEL
is
1000
ppm
(
25
mg/
kg
bw/
day).

This
chronic
study
in
dogs
is
Acceptable/
Guideline
and
satisfies
the
guideline
requirements
for
a
chronic
toxicity
study
in
dogs.
[
OPPTS
870.4100b,
OECD
452].

Dose
and
Endpoint
for
establishing
cRfD:
Chronic
NOAEL
of
25
mg/
kg/
day
(
1000
ppm),
based
on
body
weight
loss,
clinical
chemistry/
hematology
differences,
slight
anemia
and
the
presence
of
skeletal
muscle
myopathy
at
a
dose
of
125
mg/
kg/
day
(
5000
ppm).

Uncertainty
Factor
(
UF):
100;
includes
10x
for
interspecies
extrapolation
and
10x
for
intraspecies
variation.

Comments
about
Study/
Endpoint/
UF:
The
duration
of
dosing
and
the
endpoint
are
appropriate
for
this
scenario.
The
special
92­
day
study
(
1991,
MRID
No.:
42054601)
to
assess
for
thyroid
effects
of
imazaquin,
which
demonstrated
a
NOAEL
and
LOAEL
of
4.98
(
or
5)
and
245.4
mg/
kg/
day,
respectively,
based
on
slight
body
weight
decrease
and
increases
in
TSH
accompanied
by
decreases
in
T4
and
T3,
was
not
selected
for
the
NOAEL
for
the
cRfD,
because
the
NOAEL
of
5
mg/
kg/
day
for
this
study
is
an
artefact
of
dose
spacing.
The
magnitude
of
the
effects
of
imazaquin
at
245.4
mg/
kg/
day
in
the
special
thyroid
study
was
considered
relatively
small,
so
that
HED
believes
the
thyroid
and
body
weight
effects
would
not
be
present
at
a
dose
of
25
mg/
kg/
day.
In
addition,
all
other
NOAELs
for
imazaquin
from
the
available
subchronic
and
chronic
studies
are
much
higher
than
25
mg/
kg/
day.
Finally,
the
selected
NOAEL
of
25
mg/
kg/
day
based
on
the
dog
chronic
feeding
study
is
well
below
the
dose
at
which
the
thyroid
effects
were
seen
and
should
be
protective
of
any
potential
thyroid
effects
of
imazaquin.

Chronic
RfD
=
25
mg/
kg/
day
=
0.25
mg/
kg/
day
100
4.4.4
Incidental
Oral
Exposure
(
Short
and
Intermediate
Term)
Page
34
of
68
Study
Selected:
Dog
Chronic
Feeding
Study.
OPPTS:
870.4100b
MRID
No.:
00147011
EXECUTIVE
SUMMARY:
See
above
under
cRFD.

Dose
and
Endpoint:
NOAEL
of
25
mg/
kg/
day
based
on
decreased
body
weight,
changes
in
hematology
indicating
anemia
and
changes
in
clinical
chemistry
parameters.

MOE
=
100
Comments
about
Study/
Endpoint/
UF:
Body
weight
shows
an
apparent
decrease
in
the
first
4
weeks.
The
hematology
data
from
the
earliest
assessment
time
at
13
weeks
indicate
statistically
significant
changes
in
both
hematology
parameters
to
indicate
a
concern
that
the
anemia
effects
of
imazaquin
may
occur
within
the
time
frame
for
short
and
intermediate
term
incidental
oral
exposure.

4.4.5
Dermal
Absorption
A
dermal
penetration
study
is
not
available
for
imazaquin.
When
the
NOAEL
of
1000
mg/
kg/
day
from
the
rabbit
21­
day
dermal
toxicity
study
(
1985,
MRID
No.:
00146204)
is
compared
with
the
maternal
LOAEL
of
500
mg/
kg/
day
for
body
weight
effects
in
the
rabbit
oral
prenatal
developmental
toxicity
study
(
1984,
MRID
No.:
00174011),
an
upper­
bound
estimate
of
50%
dermal
absorption
is
made.
It
is
noted
that
a
LOAEL
from
the
rabbit
oral
study
is
being
compared
with
a
NOAEL
from
a
dermal
study
when
LOAELs
for
both
studies
should
normally
be
compared.
However,
since
no
LOAEL
for
the
rabbit
dermal
study
was
established,
the
highest
dose
tested
(
1000
mg/
kg/
day)
is
being
compared
to
give
a
conservative
estimate,
based
on
the
possibility
that
toxicity
may
develop
at
doses
slightly
higher
than
the
NOAEL.
This
conservative
estimate
of
50%
dermal
absorption
should
be
used
to
assess
imazaquin
dermal
exposure
and
risk.

4.4.6
Dermal
Exposure
(
Short,
Intermediate
and
Long
Term)

Study
Selected:
Chronic
toxicity­
dog
OPPTS:
870.4100b
MRID
No.:
00138972
EXECUTIVE
SUMMARY:
MRID
00138972­
see
chronic
RfD.

Dose
and
Endpoint
for
establishing
cRfD:
Chronic
NOAEL
of
25
mg/
kg/
day
(
1000
ppm),
based
on
body
weight
loss,
clinical
chemistry/
hematology
differences,
slight
anemia
and
the
presence
of
skeletal
muscle
myopathy
at
a
dose
of
125
mg/
kg/
day
(
5000
ppm).

Uncertainty
Factor
(
UF):
100
Page
35
of
68
Comments
about
Study/
Endpoint/
UF:
50%
dermal
absorption
should
be
assumed
for
risk
assessment
purposes.
The
chronic
oral
toxicity
NOAEL
of
25
mg/
kg/
day
in
dogs
(
refer
to
chronic
dietary
RfD
above
for
executive
summary),
based
on
weight
loss,
slight
anemia
and
myopathy
at
125
mg/
kg/
day,
is
appropriate
for
the
short,
intermediate
or
long
term
intervals.
The
chronic
dog
study
demonstrated
indications
of
anemia
at
the
week
13
assessment
time,
and
the
time
to
onset
of
this
condition
is
not
known
and
may
well
be
within
the
short
and
intermediate
term
exposure
intervals.
Because
there
were
no
systemic
or
dermal
effects
at
the
highest
dose
tested
in
the
21­
day
dermal
toxicity
study
(
1985,
MRID
No.:
00146204)
with
rabbits
that
demonstrated
a
NOAEL
of
1000
mg/
kg/
day,
this
route­
specific
study
was
not
selected
for
dermal
risk
assessment.
In
addition,
the
dog
study
demonstrated
anemia
as
a
critical
endpoint
and
the
rabbit
may
not
be
susceptible
to
this
condition.

Ordinarily,
when
there
is
no
toxic
effect
of
concern
demonstrated
in
the
rabbit
21­
day
dermal
study
at
the
limit
dose
(
1000
mg/
kg/
day)
and
there
are
no
indications
of
developmental,
reproductive
or
neurotoxicity,
a
dermal
exposure
assessment
is
not
deemed
necessary.
In
this
case,
a
dermal
endpoint
is
being
selected
for
imazaquin,
because
effects
noted
in
the
chronic
dog
study
suggest
that
the
dog
may
be
more
sensitive
to
imazaquin
than
the
rabbit,
especially
with
regard
to
the
induction
of
anemia.
Although
there
are
no
studies
available
to
confirm
this
(
such
studies
comparing
oral
toxicity
in
one
species
to
dermal
toxicity
in
the
rabbit
are
not
generally
conducted
or
required),
HED
is
making
the
highly
conservative
assumption
that
the
dog
is
the
most
sensitive
species
for
the
purpose
of
this
screening
level
risk
assessment.
HED
is
also
making
the
assumption
that
effects
noted
in
the
dog
study
at
13
weeks
could
occur
within
a
short­
term
(
i.
e.,
4
week)
time
frame.
Again,
there
are
no
data
to
confirm
this
assumption,
and
considering
the
slight
and
transient
nature
of
the
toxic
effects
seen
at
13
weeks,
this
assumption
may
also
be
considered
highly
conservative.
Therefore,
dermal
exposure
assessments
based
on
this
endpoint
may
be
considered
screening
level
only;
and
the
risk
assessment
team
leaves
open
the
option
to
reconsider
the
need
for
a
dermal
risk
assessment
in
future
risk
assessments
for
imazaquin.

4.4.7
Inhalation
Exposure
(
Short,
Intermediate
and
Long
Term)

Study
Selected:
Chronic
toxicity­
dog
(
long­
term)
OPPTS:
870.4100b
MRID
No.:
00138972
EXECUTIVE
SUMMARY:
See
cRFD
above.

Dose
and
Endpoint
for
establishing
cRfD:
Chronic
NOAEL
of
25
mg/
kg/
day
(
1000
ppm),
based
on
body
weight
loss,
clinical
chemistry/
hematology
differences,
slight
anemia
and
the
presence
of
skeletal
muscle
myopathy
at
a
dose
of
125
mg/
kg/
day
(
5000
ppm).

Uncertainty
Factor
(
UF):
100
Comments
about
Study/
Endpoint/
UF:
100%
absorption
of
the
inhaled
imazaquin
in
the
atmosphere
should
be
assumed
for
risk
assessment
purposes.
The
chronic
oral
toxicity
NOAEL
Page
36
of
68
of
25
mg/
kg/
day
in
dogs
(
refer
to
chronic
dietary
RfD
above
for
executive
summary),
based
on
weight
loss,
slight
anemia
and
myopathy
at
125
mg/
kg/
day,
is
appropriate
for
the
short,
intermediate
or
long
term
intervals.
The
chronic
dog
study
demonstrated
indications
of
anemia
at
the
week
13
assessment
time
and
the
time
to
onset
of
this
condition
is
not
known
and
may
well
be
within
the
short
and
intermediate
term
exposure
intervals.

4.4.8
Margins
of
Exposure
The
Margins
of
Exposure
(
MOEs)
of
concern
for
occupational
and
residential
exposure
risk
assessments
are
as
follows:

Route
of
Exposure
Duration
of
Exposure
Short­
Term
(
1­
30
Days)
Intermediate­
Term
(
1­
6
Months)
Long­
Term
(>
6
Months)

Dermal
100
100
100
Inhalation
100
100
100
For
occupational
and
residential
dermal
and
inhalation
exposure
risk
assessments
(
all
exposure
durations),
a
MOE
of
100
is
required.
The
MOE
is
based
on
the
conventional
uncertainty
factor
of
100X
(
10X
for
intraspecies
variation
and
10X
for
interspecies
extrapolation).

4.4.9
Recommendation
for
Aggregate
Exposure
Risk
Assessments
All
oral,
dermal
and
inhalation
exposures
can
be
aggregated,
as
the
toxic
endpoints
selected
to
assess
oral,
dermal
and
inhalation
risks
are
based
on
common
effects
in
dogs
(
i.
e.,
body
weight
effects,
anemia
and
blood
chemistry
changes).

4.4.10
Classification
of
Carcinogenic
Potential
Imazaquin
has
not
been
reviewed
by
the
HED
Carcinogenicity
Assessment
Review
Committee
or
its
predecessors.
However,
no
evidence
of
carcinogenicity
was
seen
in
rats
or
mice
and
the
mutagenicity
and
genetic
toxicity
studies
do
not
indicate
a
concern
for
mutagenicity.
Page
37
of
68
Table
4.4.
Summary
of
Toxicological
Doses
and
Endpoints
for
Imazaquin
for
Use
in
Human
Risk
Assessments
Exposure
Scenario
Dose
Used
in
Risk
Assessment,
UF
Special
FQPA
SF*
and
Level
of
Concern
for
Risk
Assessment
Study
and
Toxicological
Effects
Acute
Dietary
(
females
13­
49)
Not
Applicable
Not
Applicable
No
appropriate
acute
endpoint
identified
for
this
population
(
i.
e.,
no
toxic
effect
attributable
to
a
single
dose
identified).

Acute
Dietary
(
general
population)
Not
Applicable
Not
Applicable
No
appropriate
acute
endpoint
identified
for
this
population
(
i.
e.,
no
toxic
effect
attributable
to
a
single
dose
identified).

Chronic
Dietary
(
all
populations)
NOAEL
=
25
mg/
kg/
day
UF
=
100
cRfD
=
0.25
FQPA
SF
=
1
X
cPAD
=
cRfD
FQPA
SF
cPAD
=
0.25
mg/
kg/
day
Chronic
toxicity
­
dog
LOAEL
=
125
mg/
kg/
day,
based
on
weight
loss,
slight
anemia,
evidence
of
skeletal
muscle
myopathy
and
supporting
hematology/
clinical
chemistry
differences
Incidental
Oral
­
all
durations.
NOAEL
=
25
mg/
kg/
day
FQPA
SF
=
1
X
MOE
of
concern
=
100
(
Residential
and
Occupational)
Same
as
above.

Dermal
­
all
durations.
NOAEL
=
25
mg/
kg/
day
FQPA
SF
=
1
X
MOE
of
concern
=
100
(
Residential
and
Occupational)

Assume
50%
dermal
absorption.
Same
as
above.

Inhalation
­
all
durations
NOAEL
=
25
mg/
kg/
day
FQPA
SF
=
1X
MOE
of
concern
=
100
(
Residential
and
Occupational)

Assume
100%
absorption.
Same
as
above.

Cancer
(
oral,
dermal,
inhalation)
Classification:
No
evidence
of
carcinogenicity
in
mice
or
rats.
Page
38
of
68
UF
=
uncertainty
factor,
FQPA
SF
=
Special
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,
MOE
=
margin
of
exposure
*
Refer
to
Section
4.5
Page
39
of
68
4.5
Special
FQPA
Safety
Factor
The
imazaquin
risk
assessment
team
evaluated
the
potential
for
increased
susceptibility
of
infants
and
children
from
exposure
to
imazaquin
as
required
by
the
Food
Quality
Protection
Act
(
FQPA)
of
1996
according
to
the
2002
OPP
10x
Guidance
Document.
Based
on
the
hazard
data,
the
team
concluded
that
the
special
FQPA
SF
can
be
reduced
to
1X,
since
there
are
no
concerns
and
no
residual
uncertainties
for
pre­
and/
or
postnatal
toxicity
based
on
the
following
evidence.

°
Neither
the
rat
nor
rabbit
prenatal
developmental
toxicity
studies
demonstrated
developmental
toxicity
at
doses
lower
than
maternal
toxicity.
In
rabbits,
there
was
no
developmental
toxicity
at
the
highest
dose
tested.
In
the
rats,
developmental
toxicity
was
demonstrated
at
the
same
dose
demonstrating
maternal
toxicity,
and
this
dose
was
twice
the
limit
dose
for
acceptable
prenatal
developmental
toxicity
testing.

°
The
rat
multi­
generation
reproduction
study
did
not
demonstrate
either
systemic,
reproductive
or
offspring
toxicity
at
the
highest
dose
tested,
which
was
near
the
limit
dose.

The
imazaquin
risk
assessment
team
evaluated
the
quality
of
the
exposure
data;
and,
based
on
these
data,
recommended
that
the
special
FQPA
SF
be
reduced
to
1x.
This
recommendation
is
based
on
the
following:

°
The
dietary
food
exposure
assessment
utilizes
tolerance
level
residues
and
100%
crop
treated
(
CT)
information
for
all
commodities.
By
using
these
screening­
level
input
parameters,
chronic
exposures/
risks
will
not
be
underestimated.

°
The
dietary
drinking
water
assessment
utilizes
values
generated
by
models
and
associated
modeling
parameters
which
are
designed
to
provide
conservative,
health
protective,
highend
estimates
of
drinking
water
concentrations.

°
The
residential
exposure
assessment
is
conducted
in
accordance
with
HED's
residential
SOPs,
which
provide
conservative,
screening­
level
estimates
of
exposure.
By
using
these
SOPs,
residential
exposures
will
not
be
underestimated.

4.6
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
recommendations
of
its
Endocrine
Disruptor
and
Testing
Advisory
Committee
(
EDSTAC),
EPA
determined
that
there
was
a
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
Page
40
of
68
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
with
imazaquin,
there
was
no
evidence
of
estrogen
or
androgen
mediated
toxicity.
Imazaquin,
at
higher
doses,
was
demonstrated
to
increase
thyroid
stimulating
hormone
(
TSH)
and
to
have
associated
decreased
in
T4
and
T3.
However,
the
dose
level
at
which
these
changes
were
noted
is
much
higher
(~
10­
fold)
than
the
current
reference
dose
for
risk
assessment.
Therefore,
the
risk
assessment
should
be
protective
of
the
observed
endocrine/
thyroid
effects.

When
additional
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
EDSP
have
been
developed,
imazaquin
may
be
subjected
to
further
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.

5.0
Public
Health
Data
Reference:
Review
of
Imazaquin
Incident
Reports,
DP
Barcode:
D321563,
Jerome
Blondell,
10/
12/
2005
5.1
Incident
Reports
There
have
been
no
reports
of
serious
human
poisoning
associated
with
the
use
of
imazaquin.
There
have
been
a
few
reports
of
dermal
symptoms
(
primarily
skin
irritation,
itching
and
rash)
from
exposure
during
the
application
process
or
from
postapplication
exposure.
The
lack
of
serious
incidents
further
supports
HED's
characterization
of
imazaquin
as
a
low
toxicity
pesticide
with
little
potential
for
acute
effects.
The
available
incident
data
for
imazaquin
are
summarized
below:

I.
OPP
Incident
Data
System
Incident#
7203­
1:
A
pesticide
incident
occurred
in
1998,
when
a
man
accidentally
got
the
product
on
his
back
and
legs.
He
reported
skin
irritation.
No
further
information
on
the
disposition
of
the
case
was
reported.

Incident#
7205­
1:
A
pesticide
incident
occurred
in
1998,
when
a
child
played
in
an
area
that
was
treated
with
the
product
the
previous
week.
The
child
reported
a
rash.
No
further
information
on
the
disposition
of
the
case
was
reported.
Page
41
of
68
Three
minor
cases
involving
skin
reactions
and
a
legal
suit
that
did
not
provide
specific
information
on
the
symptoms
or
exposure
were
not
included
in
the
summary
above.
Note
that
including
the
three
minor
cases,
there
were
a
total
of
five
cases
involving
skin
irritation
or
rash.

II.
Poison
Control
Center
Data
­
1993
through
2001
There
were
58
reports
of
exposure
to
imazaquin
from
1993
through
2003.
However,
just
25
of
these
reports
received
follow­
up
to
determine
medical
outcome
and
just
10
of
the
25
had
symptoms
related
to
their
exposure.
The
primary
symptoms
reported
were
dermally­
related,
primarily
irritation,
itching
and
rash.

III.
California
Data
­
1982
through
2002
No
reports
of
imazaquin
poisoning
were
reported
in
California
from
1982
through
2003.

IV.
National
Pesticide
Information
Center
On
the
list
of
the
top
200
chemicals
for
which
NPIC
received
calls
from
1984­
1991,
inclusively,
imazaquin
was
not
reported
to
be
involved
in
human
incidents.

V.
NIOSH
SENSOR
Out
of
5,899
reported
cases
from
1998­
2003,
none
involved
imazaquin.

VI.
Scientific
Literature
No
scientific
literature
was
found
concerning
human
poisoning
or
other
adverse
effects
from
exposure
to
imazaquin.

5.2
Other
Imazaquin
is
not
included
in
the
Agricultural
Health
Survey
(
AHS)
Applicator
questionnaire
and
is
not
on
the
current
National
Health
and
Nutrition
Examination
Survey
(
NHANES)
list.

6.0
Exposure
Characterization/
Assessment
6.1
Dietary
Exposure/
Risk
Pathway
6.1.1
Residue
Profile
Reference:
Imazaquin.
Tolerance
Reassessment
Eligibility
Decision
(
TRED).
Summary
of
Analytical
Chemistry
and
Residue
Data;
DP
Barcode
302944;
D.
Drew;
10/
6/
05.
Page
42
of
68
Nature
of
the
Residue
The
nature
of
the
residue
in
plants
is
adequately
understood
for
the
use
of
imazaquin
on
soybeans.
Based
on
the
trace
levels
of
radioactivity
found
in
the
soybean
seed
from
an
exaggerated
application
rate,
the
apparent
extensive
degradation
of
imazaquin
into
plant
constituents,
and
the
livestock
grazing/
feeding
prohibition
of
forage,
straw
and
hay
on
current
labels,
the
residue
of
concern
for
the
use
of
imazaquin
on
soybeans
is
imazaquin,
per
se.
If
additional
uses
of
imazaquin
are
proposed,
then
additional
metabolism
data
may
be
required.

The
nature
of
residue
in
livestock
is
adequately
understood
for
the
use
of
imazaquin
on
soybeans.
Based
on
the
results
of
the
animal
metabolism
studies
where
livestock
were
dosed
at
94x
(
ruminant)
and
68x
(
poultry)
the
maximum
theoretical
dietary
burden
(
based
on
the
feeding
of
soybean
seed),
there
is
no
reasonable
expectation
of
finite
imazaquin
residues
to
occur
in
meat,
milk,
poultry,
and
eggs
(
Category
3
of
40
CFR
§
180.6(
a))
as
a
result
of
the
use
pattern
on
soybean.
Additionally,
soybean
seed
samples
had
no
detectable
residues
(<
0.05
ppm),
when
treated
at
up
to
8X
the
maximum
application
rate
of
imazaquin;
and
forage,
hay,
and
straw
are
restricted
as
feed
items.
HED
considers
the
feeding
restrictions
to
be
enforceable,
and
therefore
acceptable,
since
soybeans
are
grown
only
for
seed
and
the
feed
items
remain
under
the
control
of
the
grower.
If
additional
uses
or
additional
field
studies
result
in
detectable
residues
in
feedstuffs,
then
additional
animal
metabolism
studies
may
be
required.

Magnitude
of
the
Residue
A
tolerance
has
been
established
under
40
CFR
§
180.426
for
imazaquin
in
or
on
soybeans
at
0.05
ppm.
In
crop
field
trials
conducted
on
soybeans
using
pre­
plant
incorporated
and
post­
emergence
treatments
with
diisoproyl­
amine
salt
of
imazaquin
at
rates
of
0.25
lb
ae/
A
(
1x)
to
2
lb
ae/
A
(
8x;
one
trial),
residues
of
imazaquin
were
<
0.05
ppm
in
all
samples
including
seeds,
foliage,
and
straw.
Forage
and
hay
samples
were
not
collected.
Processing
studies
are
not
required,
because
residues
were
not
detected
in
soybean
samples
treated
at
8x
the
maximum
application
rate.

Residues
of
imazaquin
are
stable
for
up
to
24
months
on
frozen
soybean
and
corn.
The
storage
duration
of
the
crop
field
trial
soybean
samples
from
harvest
to
analysis
was
not
provided.

No
studies
pertaining
to
magnitude
of
the
residue
in
eggs,
milk
and
meat
were
submitted.
Several
raw
agricultural
and
processed
commodities
of
soybean
may
be
utilized
as
livestock
feed
items;
however,
based
on
the
results
of
the
animal
metabolism
studies
discussed
above,
there
is
no
reasonable
expectation
of
finite
imazaquin
residues
occurring
in
livestock
commodities
as
a
result
of
the
soybean
use.
Therefore,
HED
has
determined
that
feeding
studies
are
not
required
at
this
time.
HED
reserves
the
right
to
request
livestock
feeding
studies
in
the
future
if
additional
uses
on
crops
with
livestock
feed
items
are
proposed
for
registration.
Page
43
of
68
Rotational
Crops
In
a
confined
rotational
crop
study,
soybeans
were
planted
in
soil
treated
with
14C­
labeled
imazaquin
and
13C­
labeled
quinoline
(
approx.
1.5x
maximum
single
application
rate)
and
grown
to
maturity,
about
4.5
months.
Winter
wheat
was
planted
3
months
after
treatment,
and
spring
wheat
and
field
corn
were
planted
8.5
months
after
treatment.
Carrots
and
lettuce
were
also
planted
9.5
months
after
treatment.
The
total
radioactive
residue
(
TRR)
were
below
0.01
ppm
in
RACs,
except
in
corn
fodder
(
0.02
ppm)
and
in
winter
wheat
straw
(
0.07
ppm).
Sixty
percent
of
the
wheat
straw
residue
was
extractable
and
further
characterized.
The
extractable
residue
was
separated
on
HPLC
into
7
­
9
unknown
compounds,
each
at
a
level
below
0.01
ppm.

A
field
accumulation
in
rotational
crop
study
for
corn
planted
following
soybeans
was
submitted
in
order
to
support
the
reduction
of
the
corn
plant
back
interval
to
9.5
months,
instead
of
the
11
months
that
was
in
place
at
the
time.
Imazaquin
was
applied
at
a
rate
of
0.125
lb
ae/
A
in
both
pre­
plant
incorporation
and
post­
emergence
stages
(
0.25
lbs
ae/
A
total).
Soybeans
were
grown
to
maturity
and
harvested.
Corn
was
planted
281­
334
days
(
9.3
to
11
months)
after
final
imazaquin
treatment.
Corn
samples,
after
planting,
were
harvested
at
40­
41days
for
forage,
60­
93
days
for
early
silage,
84­
110
days
for
late
silage,
and
111­
181
days
for
grain
and
foddler.
No
detectable
imazaquin
residues
were
detected,
i.
e.
all
sample
detections
were
<
0.05
ppm.
Based
on
the
submitted
confined
accumulation
and
field
accumulation
in
rotational
crop
studies,
HED
was
in
favor
of
the
proposed
label
amendment
to
reduce
the
plant
back
interval
from
eleven
months
to
nine
and
a
half
months
for
corn.

Currently,
labels
specify
PBIs
from
3
to
11
months
for
most
rotated
crops.
PBIs
greater
than
11
months
are
specified
for
some
rotated
crops,
presumably
because
of
phytotoxicity
concerns.
Based
on
the
plant
back
intervals
(
PBIs)
used
in
the
confined
accumulation
study
and
field
accumulation
study,
where
no
residues
of
imazaquin
were
detected,
the
rotational
crop
restrictions
on
the
current
labels
are
adequate.
If
the
registrant
desires
reduced
rotational
crop
plant
back
intervals,
additional
field
accumulation
in
rotational
crops
data
should
be
submitted.

Analytical
Methods
Method
M­
1410
has
been
accepted
for
tolerance
enforcement
purposes
and
is
included
in
PAM,
Vol
II
as
Method
I.
The
gas
chromatography
method
uses
acidic
water
and
methanol
in
the
extraction
process
and
has
a
limit
of
quantitation
(
LOQ)
of
0.05
ppm.
The
previous
analytical
methods
(
M­
1283
and
M­
1245)
were
replaced
by
Method
M­
1410
because
the
analysis
of
freezer
stability
samples
using
Methods
M­
1283
and
M­
1245
showed
that
extraction
with
ethyl
acetate
only
extracted
about
50%
of
the
residue.
The
crop
field
samples
were
analyzed
using
Methods
M­
1283
and
M­
1245;
however,
the
fortification
results
indicated
acceptable
recovery.

Imazaquin
has
not
been
tested
for
recovery
via
FDA
Multiresidue
Protocols
(
PAM
Vol.
I),
and
it
is
unknown
whether
it
is
recoverable
by
these
methods.
Page
44
of
68
Residue
Chemistry
Deficiencies/
Regulatory
Recommendations
A
tolerance
of
0.05
ppm
has
been
established
under
40
CFR
§
180.426
for
residues
of
imazaquin
in
or
on
soybeans.
HED
supports
this
tolerance,
provided
the
following
deficiencies
and
data
gaps
are
resolved:

°
The
storage
duration
of
the
crop
field
trial
soybean
samples
from
harvest
to
analysis
was
not
provided
and
should
be
submitted.
Storage
stability
studies
indicate
that
residues
of
imazaquin
are
stable
on
soybeans
for
up
to
24
months
of
frozen
storage.

°
Multiresidue
method
data
were
not
submitted.
The
registrant
should
submit
data
pertaining
to
the
recovery
of
imazaquin
via
FDA
Multiresidue
Protocols
(
PAM
Vol.
I).

°
Residue
data
were
not
provided
for
soybean
forage
and
hay;
however,
these
data
are
not
required
provided
current
label
restrictions
prohibiting
the
grazing
and
feeding
of
forage,
straw
and
hay
to
livestock
are
maintained.

6.1.2
Chronic
Dietary
Exposure
and
Risk
Reference:
Imazaquin
Chronic
Dietary
Exposure
Assessment
for
the
Reregistration
Eligibility
Decision,
DP
Barcode:
D302943,
Susan
Stanton,
10/
20/
05
A
chronic
dietary
risk
assessment
was
conducted
for
imazaquin,
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM­
FCID,
Version
2.03),
which
uses
food
consumption
data
from
the
USDA's
Continuing
Surveys
of
Food
Intakes
by
Individuals
(
CSFII)
from
1994­
1996
and
1998.
Since
no
toxic
effects
attributable
to
a
single
(
i.
e.,
acute)
exposure
have
been
identified
for
imazaquin,
an
acute
dietary
exposure
assessment
was
not
conducted.
Also,
since
there
is
no
evidence
that
imazaquin
is
carcinogenic
to
humans,
a
dietary
cancer
assessment
was
not
conducted.

The
tier
1
chronic
assessment
assumed
that
100%
of
the
soybean
crop
is
treated
and
that
residues
of
imazaquin
are
present
at
the
tolerance
level
of
0.05
ppm
in
all
soybean
commodities,
including
processed
commodities.
Drinking
water
was
incorporated
directly
into
the
dietary
assessment
using
the
tier
1
estimated
drinking
water
concentration
for
ground
water
generated
by
the
SCIGROW
model
(
See
sec.
6.2,
below).
As
discussed
in
section
3.6.2
(
Rationale
for
Inclusion
of
Metabolites
and
Degradates),
the
residue
of
concern
in
surface
water
consists
of
parent
imazaquin
and
its
photolytic
degradates;
whereas,
the
residue
of
concern
in
groundwater
consists
of
parent
imazaquin
only.
The
SCI­
GROW
groundwater
estimate
was
selected
for
risk
assessment
purposes,
because
this
estimate
of
parent
imazaquin
only
was
higher
than
the
PRZM­
EXAMS
model
estimates
of
imazaquin
and
its
photolytic
degradates
in
surface
water.

The
resulting
dietary
exposure
estimates
are
well
below
HED's
level
of
concern
(
i.
e.,
<
100%
of
the
cPAD)
for
the
overall
U.
S.
population
and
all
population
subgroups.
Using
the
DEEM­
FCID
Page
45
of
68
software,
chronic
dietary
exposure
is
estimated
at
0.000677
mg/
kg/
day
for
the
U.
S.
population
(
0.3%
of
the
cPAD)
and
0.002208
mg/
kg/
day
(
0.9%
of
the
cPAD)
for
infants
less
than
1
year
old,
the
population
subgroup
with
the
highest
estimated
chronic
dietary
exposure
to
imazaquin.

More
than
95%
of
the
total
estimated
dietary
exposure
is
from
drinking
water.
Estimated
exposure
and
risk
from
food,
drinking
water
and
combined
food
and
drinking
water
are
summarized
below
in
Table
6.1
for
the
U.
S.
population
and
population
subgroups.

Table
6.1.
Summary
of
Chronic
Dietary
Exposure
and
Risk
for
Imazaquin1
Population
Subgroup
Food
Only
Drinking
Water
Only
Food
+
Drinking
Water
Exposure
(
mg/
kg/
day)
%
cPAD
Exposure
(
mg/
kg/
day)
%
cPAD
Exposure
(
mg/
kg/
day)
%
cPAD
General
U.
S.
Population
0.000024
0.01
0.000653
0.3
0.000677
0.3
All
Infants
(<
1
year
old)
0.000066
0.03
0.002142
0.9
0.002208
0.9
Children
1­
2
years
old
0.000053
0.02
0.000970
0.4
0.001023
0.4
Children
3­
5
years
old
0.000052
0.02
0.000908
0.4
0.000960
0.4
Children
6­
12
years
old
0.000036
0.01
0.000627
0.3
0.000663
0.3
Youth
13­
19
years
old
0.000023
0.01
0.000472
0.2
0.000496
0.2
Adults
20­
49
years
old
0.000019
0.01
0.000610
0.2
0.000629
0.3
Adults
50+
years
old
0.000015
0.01
0.000642
0.3
0.000657
0.3
Females
13­
49
years
old
0.000018
0.01
0.000608
0.2
0.000626
0.3
1The
values
for
the
population
with
the
highest
estimated
exposure
are
bolded.

6.2
Water
Exposure/
Risk
Pathway
Reference:
Drinking
Water
Assessment
for
Imazaquin
and
its
Salts;
K.
Moore;
June
21,
2005,
as
amended
on
September
27,
2005.

Potential
concentrations
of
imazaquin
and
its
monoammonium
and
monosodium
salts
in
drinking
water
were
assessed
by
the
Environmental
Fate
and
Effects
Division
(
EFED)
through
an
evaluation
of
surface
water
and
groundwater
monitoring
data
and
modeling.
Because
all
three
compounds
dissociate
in
water
to
form
the
carboxylate
anion,
they
were
treated
concurrently
in
the
assessment.

Imazaquin's
primary
use
is
as
a
broad
spectrum
herbicide
on
soybeans.
The
turf
and
ornamental
use
patterns
were
also
considered
in
EFED's
assessment.
Surface
and
groundwater
monitoring
data
were
available
from
the
United
States
Geological
Survey
(
USGS)
National
Water­
Quality
Assessment
(
NAWQA)
Program
and
from
an
additional
USGS
study
on
pesticide
concentrations
Page
46
of
68
in
high
use
areas
in
the
Midwest.
Maximum
concentrations
of
imazaquin
in
the
monitoring
data
reviewed
were
4.89
:
g
ae/
L
in
surface
water
and
0.098
:
g
ae/
L
in
groundwater.
Because
the
monitoring
studies
reviewed
are
short
term
or
not
targeted
to
detect
imazaquin,
they
are
not
likely
to
capture
peak
concentrations.
Modeling
was
used,
therefore,
to
predict
the
most
conservative
concentrations,
with
monitoring
data
used
to
confirm
that
modeling
results
are
reasonable.
Estimated
Environmental
Concentrations
(
EECs)
in
surface
water
were
modeled
using
PRZM
3.12/
EXAMS
2.98.04,
and
ground
water
concentrations
were
modeled
using
SCIGROW
(
version
2.3).

At
the
time
of
EFED's
original
assessment,
no
degradates
of
concern
had
been
identified
and
only
the
parent
compounds
were
assessed.
HED
subsequently
determined
that
the
major
surface
water
degradates
should
also
be
considered
in
the
risk
assessment.
Therefore,
EFED
repeated
the
surface
water
modeling
for
the
most
vulnerable
scenario,
turf,
with
an
updated
photolysis
half­
life
that
incorporated
these
degradates.
The
updated,
total
residue
half­
life
was
calculated
by
performing
first
order
linear
regression
on
the
log
transformed
sum
total
of
imazaquin
plus
each
of
the
four
major
degradates
at
each
sampling
point.
Since
these
degradates
are
not
expected
to
form
in
ground
water,
the
ground
water
EECs
include
the
parent
compounds
only.
The
surface
and
ground
water
modeling
results
are
presented
in
Table
6.2.
Note
that
all
concentrations
reported
in
this
assessment
are
in
acid
equivalents
(
ae).

Table
6.2.
Imazaquin
EECs
1
Surface
water
(
PRZM
/
EXAMS)
2
Groundwater
(
SCIGROW)
3
Crop
Scenario
Acute
(
Peak)
Chronic
(
Annual
average)
Acute
&
Chronic
Soybeans
1.8
µ
g
ae/
L
0.4
µ
g
ae/
L
3.8
µ
g
ae/
L
Ornamental
1.9
µ
g
ae/
L
1.0
µ
g
ae/
L
15.6
µ
g
ae/
L
Turf
­
1
app.
15.2
µ
g
ae/
L
5.0
µ
g
ae/
L
15.6
µ
g
ae/
L
Turf
­
1
app.
4
16.0
µ
g
ae/
L
6.7
µ
g
ae/
L
15.6
µ
g
ae/
L
Turf
­
2
app.
20.0
µ
g
ae/
L
7.6
µ
g
ae/
L
31.1
µ
g
ae/
L
Turf
­
2
app.
4
21.8
µ
g
ae/
L
11.6
µ
g
ae/
L
31.1
µ
g
ae/
L
1
All
EECs
are
for
parent
compound
only,
unless
otherwise
specified.

2
From
the
PRZM­
EXAMS
­
Index
Reservoir
model.
Input
parameters
are
based
on
maximum
application
rates,
an
aerobic
soil
metabolic
half­
life
of
630
days
(
3
times
the
reported
value),
an
anaerobic
soil
metabolic
half­
life
of
"
stable",
an
aerobic
aquatic
degradation
half­
life
of
1260
days
(
no
data
available
­
2
times
the
aerobic
soil
metabolic
half­
life),
an
anaerobic
aquatic
degradation
half­
life
of
"
stable",
an
aqueous
photolysis
half­
life
of
0.9
days,
a
hydrolysis
half­
life
of
"
stable",
vapor
pressure
of
<
2
x
10­
8
and
a
median
Koc
of
17.5
ml/
g.
A
percent
cropped
area
(
PCA)
adjustment
factor
of
0.41
was
assumed
for
soybeans.
3
From
the
SCI­
GROW
model.
Input
parameters
based
on
maximum
application
rates,
an
aerobic
soil
metabolic
half­
life
of
210
days
and
a
median
KOC
of
17.5
ml/
g.
4
The
surface
water
EECs
include
parent
imazaquin
and
its
major
degradates.
The
ground
water
EECs
include
parent
compound
only.
Page
47
of
68
The
highest
imazaquin
concentration
was
estimated
for
groundwater,
based
on
2
applications
to
turf
at
0.5
lbs.
ae/
acre.
This
value
(
31.1
ppb/
0.031
ppm)
was
used
as
a
point
estimate
to
assess
exposure
to
imazaquin
from
drinking
water
in
the
dietary
assessment.

6.3
Residential
(
Non­
Occupational)
Exposure/
Risk
Pathway
Reference:
Imazaquin:
Residential
Exposure
Assessment
and
Recommendations
for
the
Tolerance
Reassessment
Eligibility
Decision
(
TRED);
DP
Barcode:
D302942;
Seyed
Tadayon;
10/
06/
2005
Imazaquin
may
be
used
in
residential
settings
on
turfgrass
and
ornamentals,
including
turfgrass
and
ornamentals
on
golf
courses.
The
residential
use
of
imazaquin
is
limited
to
outdoor
applications.
There
is
a
potential
for
short­
term
(
1
to
30
days
in
duration)
non­
occupational
exposure
in
residential
settings
during
the
application
process
for
homeowners
who
use
products
containing
imazaquin.
There
is
also
a
potential
for
short­
term
exposure
of
children
and
adults
entering
areas
that
have
been
treated
with
imazaquin.
As
a
result,
short­
term
risk
assessments
have
been
completed
for
both
residential
handler
and
postapplication
exposure
scenarios.
Due
to
the
episodic
nature
of
imazaquin
applications,
intermediate­
and
long­
term
exposures
are
not
anticipated
and,
therefore,
have
not
been
assessed.

6.3.1
Residential
Handler
Exposures
The
Agency
uses
the
term
"
handlers"
to
describe
those
individuals
who
are
involved
in
the
pesticide
application
process
(
i.
e.,
the
mixing,
loading
or
applying
of
pesticides).
The
agency
believes
that
there
are
distinct
tasks
related
to
applications
and
that
exposures
can
vary
depending
on
the
specifics
of
each
task.
Residential
handler
exposures
are
assessed
somewhat
differently
than
occupational
handler
exposures
by
the
Agency,
as
described
below:

°
Residential
handler
exposure
scenarios
are
considered
to
be
of
short­
term
duration
only,
due
to
the
episodic
nature
of
homeowner
applications;

°
A
tiered
approach
based
on
increasing
levels
of
personal
protective
equipment
(
PPE)
is
not
used
in
residential
handler
risk
assessments.
Homeowner
handler
assessments
assume
that
individuals
are
wearing
shorts,
short­
sleeved
shirts,
socks
and
shoes.

°
Homeowner
handlers
are
expected
to
complete
all
tasks
associated
with
the
use
of
a
pesticide
product,
including
mixing/
loading,
if
needed,
and
the
application;

°
Label
directions
and
application
rates
for
residential
(
i.
e.,
homeowner)
products
serve
as
the
basis
for
exposure
and
risk
calculations,
rather
than
commercial
label
rates
and
directions
for
use;
and
Page
48
of
68
°
Area/
volumes
of
spray
or
chemical
used
in
the
risk
assessment
are
based
on
HED
guidance
specific
to
residential
use
patterns.

6.3.1.1
Residential
Handler
Exposure
Scenarios
Residential
handler
exposure
is
likely
during
the
use
of
imazaquin
on
turf
and
ornamentals
in
a
variety
of
outdoor
environments.
The
anticipated
use
patterns
and
current
labeling
indicate
several
major
residential
exposure
scenarios
based
on
the
types
of
equipment
and
techniques
that
can
potentially
be
used
to
make
imazaquin
applications.
The
quantitative
exposure/
risk
assessment
developed
for
residential
handlers
is
based
on
the
following
scenarios:

Mixer/
Loader/
Applicators:

(
1)
Liquid
Concentrate:
Hose­
end
Sprayer
­
Turf
Application
(
2)
Liquid
Concentrate:
Hand
Held
Pump
Sprayer
­
Ornamentals/
Shade
Tree
Application
(
3)
Liquid
Concentrate:
Ready
to
Use
Sprayer
­
Turf
Application
6.3.1.2
Data
and
Assumptions
For
Residential
Handler
Exposure
Scenarios
A
series
of
assumptions
served
as
the
basis
for
the
handler
risk
assessments.
The
assumptions
used
in
the
risk
assessment
calculations
are
detailed
below:

°
Both
dermal
and
inhalation
short­
term
exposures
may
occur
during
the
handling
of
imazaquin
in
residential
settings.
Dermal
and
inhalation
exposures
were
each
assessed,
based
on
the
NOAEL
of
25
mg/
kg/
day
from
the
dog
chronic
toxicity
study.
For
the
dermal
assessment,
50%
dermal
absorption
of
imazaquin
was
assumed;
for
the
inhalation
assessment,
100%
absorption
of
inhaled
imazaquin
in
the
atmosphere
was
assumed.

°
No
chemical­
specific
exposure
data
for
imazaquin
were
available
for
use
in
the
residential
handler
exposure
assessment.
Therefore,
HED
used
standard
unit
exposure
values
derived
from
studies
conducted
by
the
Outdoor
Residential
Exposure
Task
Force
(
ORETF)
to
estimate
handler
exposure
and
risk.

°
HED
always
considers
the
maximum
application
rates
allowed
by
labels
in
its
risk
assessments.
If
additional
information,
such
as
average
or
typical
rates,
is
available,
these
values
also
may
be
used
to
allow
risk
managers
to
make
a
more
informed
risk
management
decision.
Average/
typical
application
rates
were
not
available
for
the
residential
uses
of
imazaquin.
Therefore,
the
maximum
homeowner
application
rates
were
assumed.

°
Residential
risk
assessments
are
based
on
estimates
of
what
homeowners
would
typically
treat,
such
as
the
size
of
a
lawn.
The
estimates
used
for
the
imazaquin
assessment
were
taken
from
HED's
Exposure
Science
Advisory
Committee
Policy
12:
Recommended
Page
49
of
68
Revisions
To
The
Standard
Operating
Procedures
For
Residential
Exposure
Assessment,
which
was
completed
on
February
22,
2001;
and
on
professional
judgement.
The
daily
volumes
handled
and
area
treated
that
were
assumed
for
each
residential
scenario
are
provided
in
Table
6.3.1.3.

6.3.1.3
Residential
Handler
Exposure
and
Risk
Estimates
Dermal
and
inhalation
potential
exposures
for
residential
handlers
were
calculated
as
follows:

Exposure
Dose
(
mg/
kg/
day)
=
UE
x
AR
x
A
x
AB
BW
Where:
UE
=
unit
exposure
from
ORETF
study
data
(
mg/
lb
ai
or
µ
g/
lb
ai)
AR
=
maximum
application
rate
(
lb
ai/
acre
or
lb
ai/
gal)
A
=
maximum
area
treated
(
acres/
day
or
gal/
day)
AB
=
absorption
value
(
Dermal
absorption
=
50%;
inhalation
absorption
=
100%)
BW
=
body
weight
(
70
kg)

For
handler
short­
term
exposure,
the
margin
of
exposure
(
MOE)
was
calculated
as
follows:

Inhalation
MOE
=
NOAEL
(
25
mg/
kg/
day)
Inhalation
Exposure
Dose
Dermal
MOE=
NOAEL
(
25
mg/
kg/
day)
Dermal
Exposure
Dose
MOE
TOTAL
=
1
(
1/
Dermal
MOE
)
+
(
1/
Inhalation
MOE)

The
dermal
and
inhalation
exposures
were
combined
for
the
imazaquin
handler
risk
assessment,
because
exposure
is
expected
via
both
routes
and
the
toxicity
endpoints
for
the
dermal
and
inhalation
routes
of
exposure
are
the
same.
The
resulting
dermal,
inhalation
and
combined
residential
handler
risk
estimates
are
presented
in
Table
6.3.1.3
below.
Page
50
of
68
Table
6.3.1.3:
Imazaquin
Short­
Term
Residential
Handler
Exposure
and
Risks
Estimates
Exposure
Scenario
Target
Application
Ratea
Area
Treated
Dailyb
Dermal
Unit
Exposure
(
mg/
lb
ai)
Inhalation
Unit
Exposure
(
Ug/
lb
ai)
Dermal
Dose
d
(
mg/
kg/
day)
Inhalation
Dose
e
(
mg/
kg/
day)
MOE
(
HED's
level
of
concern
=
100)

Dermalf
Inhalation
g
Dermal
+

Inhalation
h
Mixer/
Loader/
Applicator
Mixing/
Loading/
Applying
Liquid
Concentrates
with
Hose­
End
Sprayer
(
Residential
ORETF
data)
(
1)
Turf
0.38/
A
0.5
acre
11
17
0.015
0.000046
1,700
550,000
1,700
Mixing/
Loading/
Applying
Liquid
Concentrates
with
a
Hand
Held
Pump
(
ORETF
)
sprayer(
2)
Ornamental
s
0.006
lb
ai/
gal
1
gal
38
2.7
0.0016
0.0000002
15,400
125,000,000
15,400
Applying
Ready
to
Use
sprayer
(
ORETF)(
3)
Turf
0.006
lb
ai/
gal
1
gal
54
19
0.0023
0.0000016
11,000
15,625,000
11,000
a
Application
rates
are
the
maximum
application
rates
determined
from
EPA
registered
labels
for
imazaquin.

b
Amount
handled
per
day
values
are
EPA
estimates.

c
Attire
is
short­
sleeve
shirt,
short
pants,
and
no
gloves
and
no
respirator.

d
Dermal
Dose
=
application
rate
x
area
treated
x
dermal
unit
exposure
x
%
DA
(
50)
÷
70
e.
Inhalation
Dose
=
application
rate
x
area
treated
x
inhalation
unit
exposure
÷
70
f.
Dermal
MOE
=
NOAEL
(
25mg/
kg/
day)
/
dermal
daily
dose
(
mg/
kg/
day),

g.
Inhalation
MOE
=
NOAEL
(
25
mg/
kg/
day)
/
inhalation
daily
dose
(
mg/
kg/
day)

h
MOE
TOTAL
=
1
(
1/
Dermal
MOE
)
+
(
1/
Inhalation
MOE)
Page
51
of
68
MOEs
of
less
than
100
indicate
exposures
of
risk
concern.
Since
all
of
the
estimated
combined
dermal/
inhalation
MOEs
for
residential
handlers
of
imazaquin
are
well
above
100,
the
estimated
exposures
do
not
exceed
the
Agency's
level
of
concern
for
risk
assessments
in
non­
occupational
settings.

6.3.2
Residential
Postapplication
Exposures
6.3.2.1
Residential
Postapplication
Exposure
Scenarios
Individuals
of
varying
ages
can
potentially
be
exposed
to
imazaquin
when
they
are
in
areas
that
have
been
previously
treated.
Postapplication
exposure
scenarios
were
developed
for
each
residential
setting
where
imazaquin
can
be
used.
The
scenarios
assessed
include:

Residential
Adults:
These
individuals
are
members
of
the
general
population
that
are
exposed
to
chemicals
by
engaging
in
activities
at
their
residences
(
e.
g.,
on
their
lawns)
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
are
usually
addressed
by
HED
in
risk
assessments
by
considering
a
representative
activity
as
the
basis
for
the
exposure
calculation.

Residential
Children:
Children
are
members
of
the
general
population
that
can
also
be
exposed
at
their
residences
(
e.
g.,
on
lawns
and
other
residential
turfgrass
areas).
These
kinds
of
exposures
are
attributable
to
a
variety
of
activities
such
as
playing
outside.
Toddlers
have
been
selected
as
the
sentinel
(
representative)
children's
population
for
turf.
Children
are
addressed
by
HED
in
risk
assessments
by
considering
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
imazaquin
labels.
The
Agency
used
this
guidance
to
define
the
adult
and
toddler
exposure
scenarios
included
in
this
postapplication
exposure
assessment.
The
assessed
exposure
scenarios
are
summarized
below:

Toddlers:

C
Hand­
to­
mouth
activity
on
treated
turf:
Postapplication
exposure
among
toddlers
from
incidental
non­
dietary
ingestion
of
pesticide
residues
on
treated
turf
from
hand­
to­
mouth
transfer.

°
Object­
to­
mouth
activity
on
treated
turf:
Postapplication
exposure
among
toddlers
from
incidental
non­
dietary
ingestion
of
pesticide
residues
on
treated
turf
from
object­
to­
mouth
transfer.
Page
52
of
68
C
Soil
ingestion
activity
on
treated
turf:
Postapplication
exposure
among
toddlers
from
incidental
non­
dietary
ingestion
of
pesticide
residues
from
ingesting
soil
in
a
treated
turf
area.

°
High
contact
activities
on
treated
turf:
Postapplication
exposure
among
toddlers
from
dermal
contact
with
treated
turf.

Adults:

°
High
contact
activities
on
treated
turf:
Postapplication
exposure
among
adults
from
dermal
contact
with
treated
turf.

°
Mowing
turf:
Postapplication
exposure
among
adults
from
dermal
contact
with
treated
turf
during
mowing
activities.

°
Golf
Course:
Postapplication
exposure
among
adults
from
dermal
contact
with
treated
turf
on
golf
courses.

6.3.2.2
Data
&
Assumptions
for
Residential
Postapplication
Exposure
Scenarios
A
series
of
assumptions
served
as
the
basis
for
the
residential
postapplication
risk
assessments.
Each
assumption
is
detailed
below.

°
Postapplication
inhalation
exposures
are
expected
to
be
minimal;
therefore,
HED
considered
only
dermal
and
incidental
oral
exposures
in
the
postapplication
risk
assessments.

°
HED
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
behaviors
associated
with
the
exposed
population.
For
imazaquin,
HED
has
combined
postapplication
risks
for
turf
scenarios
involving
toddlers
­
i.
e.,
dermal
+
oral
risks
(
handto
mouth,
object­
to­
mouth
and
soil
ingestion).

°
The
body
weight
of
an
average
adult
(
70
kilograms)
is
used
for
assessing
dermal
risks
to
adults.

°
Exposures
of
adults
and
children
on
treated
turf
have
been
assessed
using
the
latest
Agency
approaches
for
these
scenarios,
including:

<
A
dermal
absorption
value
of
50%
was
used
for
estimating
risk
in
this
assessment.
Page
53
of
68
<
5
percent
of
the
application
rate
has
been
used
to
calculate
the
0­
day
residue
levels
for
assessing
risks
from
dermal
and
hand­
to­
mouth
exposures,
since
imazaquinspecific
turf
transferable
residue
(
TRR)
data
are
not
available.

<
20
percent
of
the
application
rate
has
been
used
to
calculate
the
0­
day
residue
levels
for
assessing
risks
from
object­
to­
mouth
behaviors.
A
higher
percent
transfer
has
been
used
for
object­
to­
mouth
behavior
because
it
involves
a
teething
action
believed
to
be
more
analogous
to
dislodgeable
foliar
residue
(
DFR)/
leaf
wash
sample
collection
where
20
percent
is
also
used.

<
The
transfer
coefficients
used
are
those
presented
during
the
1999
Agency
presentation
before
the
FIFRA
Science
Advisory
Panel
that
have
been
adopted
in
routine
practice
by
HED.

<
3
year
old
toddlers
are
expected
to
weigh
15
kilograms
(
representing
an
average
weight
from
years
one
to
six).

<
Short­
term
hand­
to­
mouth
exposures
are
based
on
a
frequency
of
20
events/
hour.
A
surface
area
per
event
of
20
cm2
representing
the
palmar
surfaces
of
three
fingers
is
assumed.

<
Saliva
extraction
efficiency
is
assumed
to
be
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
cm2
surface
area.

<
Exposure
durations
for
turfgrass
scenarios
are
expected
to
be
2
hours
based
on
information
in
the
Agency's
Exposure
Factors
Handbook
<
Soil
residues
are
contained
in
the
top
centimeter
and
soil
density
is
0.67
mL/
gram.

<
Dermal,
hand­
to­
mouth,
object­
to­
mouth
and
soil
ingestion
risks
are
combined
to
represent
an
overall
risk
from
exposure
to
treated
turf.

°
Postapplication
residential
risks
are
based
generally
on
maximum
application
rates
or
values
specified
in
the
SOPs
For
Residential
Exposure
Assessment.

°
The
Jazzercize
approach
is
the
basis
for
the
dermal
transfer
coefficients
from
turfgrass
as
described
in
HED's
Series
875
guidelines,
SOPs
For
Residential
Exposure
Assessment,
and
the
1999
FIFRA
SAP
Overview
document.
Page
54
of
68
6.3.2.3
Residential
Postapplication
Exposure
and
Risk
Estimates
Short­
term
postapplication
exposures
and
risks
for
toddlers
and
adults
based
on
the
above
assumptions
are
summarized
in
Tables
6.3.2.3a
and
6.3.2.3b.

Table
6.3.2.3a:
Short­
Term
Postapplication
Residential
Risk
Estimates
from
Oral
and
Dermal
Exposure
of
Toddlers
to
Imazaquin
Exposure
Scenario
Route
of
Exposure
Population
Application
Ratea
Ave.
Daily
Dose
(
mg/
kg/
day)
MOEb
Residential
Turf
(
High
Contact
Activities)
Dermal
Toddler
0.5
lb.
a.
i./
A
0.1
260
Hand
to
Mouth
Activity
on
Turfd
Oral
0.007
3,400
Object
to
Mouth
Activity
on
Turfe
0.0019
13,400
Incidental
Soil
Ingestionf
0.0003
1,000,000
a
Application
rates
represent
maximum
label
rates
from
current
EPA
registered
labels
.
b
MOEs
calculated
using
residues
which
would
be
found
on
day
of
treatment.
MOE
=
NOAEL
(
25
mg/
kg/
day)/
Ave.
Daily
Dose
(
mg/
kg/
day).
An
MOE
of
100
represents
HED's
level
of
concern.
c
Dermal
Dose
Calculation:
TTR(
ug/
cm2)
x
0.001
(
mg/
ug)
x
Transfer
Coefficient
(
cm2/
hr)
x
Exposure
Time
(
hr/
day)
x
Dermal
Absorption
(%)
÷
Body
Weight
(
kg)
d
Hand­
to­
mouth
Dose
Calculation:
oral
dose
to
child
(
1­
6
year
old)
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
µ
g/
cm2)]
x
median
surface
area
for
1­
3
fingers
(
20
cm2/
event)
x
hand­
to­
mouth
rate
(
20
events/
hour)
x
exp.
time
(
2
hr/
day)
x
50%
saliva
extraction
factor
x
0.001
mg/:
g]
/
bw
(
15
kg
child).
e
Object
to
Mouth
Activity
on
­
Turf
Dose
Calculation:
oral
dose
to
child
(
1­
6
year
old)
on
the
day
of
treatment
=
[
application
rate
(
lb
ai/
acre)
x
fraction
of
residue
dislodgeable
(
5%)
x
11.2
(
conversion
factor
to
convert
lb
ai/
acre
to
µ
g/
cm2)]
x
median
surface
area
for
1­
3
fingers
(
25
cm2/
event)
x
hand­
to­
mouth
rate
(
20
events/
hour)
x
0.001
mg/:
g]]
/
bw
(
15
kg
child).
f
Incidental
Soil
ingestion
­
Dose
Calculation:
oral
dose
to
child
(
1­
6
year
old)
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
µ
g/
lb
conversion
factor
x
2.47E­
08
acre/
cm2
conversion
factor
x
0.67
cm3/
g
soil
conversion
factor)
x
100
mg/
day
ingestion
rate
x
1.0E­
06
g/
µ
g
conversion
factor]
/
bw
(
15
kg).

Note:
Assumptions
used
in
dose
calculations
(
e.
g.,
transfer
coefficients)
are
from
Residential
SOPs
(
revised
2/
01).

Table
6.3.2.3b:
Short­
Term
Postapplication
Residential
Risk
Estimates
from
Dermal
Exposure
of
Adults
to
Imazaquin
Exposure
Scenario
Route
of
Exposure
Population
Application
Ratea
Ave.
Daily
Doseb
(
mg/
kg/
day)
MOEc
Residential
Turf
(
High
Contact
Activities)

Dermal
Adult
0.5
lb.
a.
i./
A
0.06
430
Mowing
Turf
0.002
12,500
Golf
Course
0.004
6,250
a
Application
rates
represent
maximum
label
rates
from
current
EPA
registered
labels
.
b
Dermal
Dose
Calculation:
TTR(
ug/
cm2)
x
0.001
(
mg/
ug)
x
Transfer
Coefficient
(
cm2/
hr)
x
Exposure
Time
(
hr/
day)
x
Dermal
Absorption
(%)
÷
Body
Weight
(
kg)
c
MOEs
calculated
using
residues
which
would
be
found
on
day
of
treatment.
MOE
=
NOAEL
(
25
mg/
kg/
day)/
Ave.
Daily
Dose
(
mg/
kg/
day).
An
MOE
of
100
represents
HED's
level
of
concern.

Note:
Assumptions
used
in
dose
calculations
(
e.
g.,
transfer
coefficients)
are
from
Residential
SOPs
(
revised
2/
01).
Page
55
of
68
The
Agency
aggregates
risk
values
resulting
from
separate
postapplication
exposure
scenarios
when
it
is
likely
they
can
occur
simultaneously
based
on
the
use
pattern
and
the
behavior
associated
with
the
exposed
population.
For
imazaquin,
the
Agency
aggregated
risk
values
(
i.
e.,
MOEs)
for
postapplication
exposures
of
toddlers
associated
with
turf
applications
by
combining
risks
from
all
dermal
and
oral
exposures.
The
combined
risks
are
shown
below
in
Table
6.3.2.3c.

Table
6.3.2.3c:
Short­
term
(
aggregate)
Toddler
Risk
from
Turf
Uses
of
Imazaquin
Exposure
Scenario
Margins
of
Exposure
(
MOEs)
(
UF=
100)
Dermal
Oral
(
Non­
Dietary)
Total
Non­
Dietary
Riska
Short­
term
Exposures
Toddler
Turf:
0.5
lb
ai/
A
High
Contact
Activities
260
N/
A
260
Hand
to
Mouth
N/
A
3400
Object
to
Mouth
N/
A
13,400
Incidental
Soil
Ingestion
N/
A
1,000,000
a
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.

The
aggregated
residential
risk
MOE
is
>
100
and
is,
therefore,
not
of
concern.

6.3.3
Other
(
Spray
Drift,
etc.)

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,
spray
drift
could
also
be
a
potential
source
of
exposure
with
ground
application
methods.
Imazaquin
may
be
applied
to
soybeans
using
ground
or
aerial
equipment.
As
indicated
in
this
assessment,
applications
of
imazaquin
directly
to
residential
turf
do
not
result
in
exposures
of
concern.
Based
on
this
assessment,
HED
believes
it
is
unlikely
that
there
is
a
higher
potential
for
risk
from
exposure
to
spray
drift
from
agricultural
uses
of
this
chemical.

7.0
Aggregate
Risk
Assessments
and
Risk
Characterization
In
accordance
with
the
FQPA,
HED
must
consider
and
aggregate
(
add)
pesticide
exposures
and
risks
from
three
major
sources:
food,
drinking
water
and
residential
exposures.
In
an
aggregate
assessment,
exposures
from
relevant
sources
are
added
together
and
compared
to
quantitative
estimates
of
hazard
(
e.
g.,
a
NOAEL
or
PAD),
or
the
risks
themselves
can
be
aggregated.
When
aggregating
exposures
and
risks
from
various
sources,
HED
considers
both
the
route
and
duration
of
exposure.

For
imazaquin,
as
for
most
pesticide
active
ingredients,
water
monitoring
data
are
considered
inadequate
to
determine
surface
and
ground
water
drinking
water
exposure
estimates,
so
model
estimates
have
been
used
to
estimate
residues
in
drinking
water
(
EDWCs).
In
order
to
determine
if
aggregate
risks
are
of
concern,
HED
has
historically
calculated
drinking
water
levels
of
comparison,
or
DWLOCs.
The
DWLOC
is
the
maximum
amount
of
a
pesticide
in
drinking
water
that
would
be
acceptable
in
light
of
combined
exposure
from
food
and
residential
pathways.
The
Page
56
of
68
calculated
DWLOCs
were
then
compared
to
the
EDWCs
provided
by
EFED
to
determine
if
a
potential
concern
existed
for
dietary
exposure
to
residues
in
drinking
water.

In
order
to
fully
implement
the
requirements
of
FQPA,
HED
and
EFED
have
been
working
toward
refining
the
screening­
level
DWLOC
approach
to
conducting
aggregate
risk
assessments
that
combine
exposures
across
all
pathways.
As
part
of
this
process,
EFED
and
HED
have
agreed
that
EDWCs
can
be
used
directly
in
dietary
exposure
assessments
to
calculate
aggregate
dietary
(
food
+
water)
risk.
This
is
done
by
using
the
relevant
model
value
as
a
residue
for
drinking
water
(
all
sources)
in
the
dietary
exposure
assessment.
The
principal
advantage
of
this
approach
is
that
the
actual
individual
body
weight
and
water
consumption
data
from
the
CSFII
are
used,
rather
than
assumed
weights
and
consumption
for
broad
age
groups.
This
refinement
has
been
used
in
estimating
the
dietary
exposure
component
in
the
imazaquin
aggregate
risk
assessments.

7.1
Acute
Aggregate
Risk
A
toxicological
endpoint
of
concern
attributable
to
a
single
dose
has
not
been
identified
for
imazaquin.
Therefore,
an
acute
aggregate
risk
assessment
has
not
been
conducted.

7.2
Short­
Term
Aggregate
Risk
Short­
term
aggregate
exposure
takes
into
account
short­
term
residential
exposure
plus
average
exposure
levels
from
residues
of
imazaquin
in
food
and
water
(
considered
to
be
a
background
exposure
level).
The
registered
residential
uses
of
imazaquin
constitute
short­
term
exposure
scenarios,
and
endpoints
have
been
selected
for
short­
term
dermal,
incidental
oral
and
inhalation
exposures.
The
acceptable
MOE
for
short­
term
exposure
is
100
for
all
routes
of
exposure.
The
dermal,
oral
and
inhalation
routes
may
be
combined
because
of
their
common
toxicity
endpoints
(
body
weight
effects,
anemia
and
blood
chemistry
changes)
and
NOAELs
(
all
25
mg/
kg/
day).

HED
conducted
short­
term
aggregate
risk
assessments
for
children
and
adults,
as
follows:

Children:
Children
may
be
exposed
to
imazaquin
residues
in
the
diet
(
food
and
water)
or
from
their
activities
in
residential
areas
previously
treated
with
imazaquin
products
(
i.
e.,
postapplication
exposure).
Estimated
chronic
dietary
exposure
for
children,
1
to
2
years
old
(
the
children's
subgroup
with
the
highest
estimated
dietary
exposure),
was
combined
with
the
estimated
shortterm
residential
postapplication
exposure
for
toddlers
and
compared
to
the
NOAEL
of
25
mg/
kg/
day
to
estimate
aggregate
risk
for
children.

The
short­
term
aggregate
risk
assessment
for
children
is
an
unrefined,
screening
level
assessment,
based
on
high­
end
estimates
of
imazaquin
residues
in
food
and
drinking
water,
as
well
as
screening
level
estimates
of
residential
exposure.
The
resulting
estimated
short­
term
aggregate
risk
is
shown
below
in
Table
7.2a.
Page
57
of
68
Table
7.2a
Estimated
Short­
Term
Aggregate
Risk:
Children
NOAEL
mg/
kg/
day
Level
of
Concern1
Dietary
MOE2
Aggregate
Residential
MOE3
Aggregate
MOE
(
Dietary
and
Residential)
4
Children,
1­
2
yrs.
old5
25
100
24,400
260
257
1
Level
of
Concern
(
MOE)
based
on
10x
UF
for
interspecies
extrapolation
and
10x
UF
for
intraspecies
variation.
2
Dietary
MOE
=
NOAEL
(
25
mg/
kg/
day)
÷
Chronic
Dietary
exposure
(
0.001023
mg/
kg/
day)
=
24,400.
Dietary
exposure
from
Table
6.1.
3
Aggregate
Residential
MOE
includes
estimated
dermal
(
high
contact
activities)
and
oral
(
hand­
to­
mouth,
object­
to­
mouth
and
incidental
soil
ingestion)
short­
term
exposures
(
see
Table
6.3.2.3c).
4
Aggregate
MOE
calculated
using
the
following
formula:
1
÷
(
1/
MOEDietary
+
1/
MOEResidential
Aggregate)
=
Aggregate
MOE;
[
1
÷
(
1/
24,400
+
1/
260)
=
257]
5
Children's
population
subgroup
with
highest
dietary
(
food
+
water)
exposure.

The
estimated
short­
term
aggregate
MOE
for
children
is
greater
than
100;
therefore,
estimated
aggregate
risk
for
children
does
not
exceed
HED's
level
of
concern.

Adults:
Adults
may
be
exposed
to
imazaquin
residues
in
the
diet
(
food
and
water),
while
applying
imazaquin
products
to
turfgrass
and
ornamentals
(
residential
handler
exposure),
or
from
their
activities
(
mowing
grass,
golfing,
etc.)
in
residential
or
recreational
areas
previously
treated
with
imazaquin
(
postapplication
exposure).
It
is
possible,
although
not
likely,
that
all
three
types
of
exposure
could
occur
in
a
short­
term
time
frame.
Therefore,
to
provide
a
high­
end,
screening
level
estimate
of
short­
term
aggregate
risk,
HED
combined
the
estimated
chronic
dietary
exposure
for
adults
over
50
years
old
(
the
adult
population
with
the
highest
estimated
dietary
exposure),
with
the
estimated
residential
handler
and
postapplication
exposures
from
the
highest
exposure
scenarios
for
adults.
The
resulting
screening
level
aggregate
risk
estimate
for
adults
is
presented
in
Table
7.2b.

Table
7.2b
Estimated
Short­
Term
Aggregate
Risk:
Adults
NOAEL
mg/
kg/
day
Level
of
Concern1
Dietary
MOE2
Residential
Handler
MOE3
Residential
Postapplication
MOE4
Aggregate
MOE
(
Dietary
and
Residential)
5
Adults,
50+
years
old6
25
100
38,000
1,700
430
340
1
Level
of
Concern
(
MOE)
based
on
10x
UF
for
interspecies
extrapolation
and
10x
UF
for
intraspecies
variation.
2
Dietary
MOE
=
NOAEL
(
25
mg/
kg/
day)
÷
Chronic
Dietary
exposure
(
0.000657
mg/
kg/
day)
=
38,000.
Dietary
exposure
from
Table
6.1.
3
Residential
Handler
MOE
(
dermal
+
inhalation),
based
on
liquid
application
to
turf
using
a
hose­
end
sprayer
(
the
scenario
with
the
highest
estimated
handler
exposure
­
see
Table
6.3.1.3).
Page
58
of
68
4
Residential
Postapplication
MOE,
based
on
the
"
jazzercise"
high
contact
activity
turf
scenario
(
the
scenario
with
the
highest
estimated
postapplication
exposure
­
see
Table
6.3.2.3b).
5
Aggregate
MOE
calculated
using
the
following
formula:
1
÷
(
1/
MOEDietary
+
1/
MOEResidential
Handler
+
1/
MOEResidential
Postapplication)
=
Aggregate
MOE;
[
1
÷
(
1/
38,000
+
1/
1,700
+
1/
430)
=
340]
6
Adult
population
subgroup
with
highest
dietary
(
food
+
water)
exposure.

As
noted
above,
the
short­
term
aggregate
assessment
for
adults
is
a
screening
level
assessment,
which
assumes
that
dietary,
residential
handler
and
residential
postapplication
exposures
occur
simultaneously
over
a
short
period
of
time
(
1
to
30
days).
It
is
also
based
on
the
residential
handler
and
postapplication
exposure
scenarios
expected
to
result
in
the
highest
exposures,
as
well
as
screening
level,
unrefined
estimates
of
imazaquin
in
food
and
drinking
water.
The
resulting
aggregate
MOE
for
adults
of
340
is
above
100;
therefore,
the
estimated
aggregate
risk
for
adults
using
these
screening
level
assumptions
does
not
exceed
HED's
level
of
concern.

Note
Regarding
the
Inclusion
of
Dermal
Exposures
in
the
Short­
Term
Aggregate
Risk
Assessment:
The
short­
term
aggregate
risk
assessment
includes
estimated
risks
from
dermal
exposure
to
imazaquin.
As
discussed
in
section
4.4.6
(
Dermal
Exposure
(
Short,
Intermediate
and
Long
Term)),
the
decision
to
conduct
a
dermal
assessment
was
based
on
highly
conservative
assumptions
that
may
be
revisited
for
future
imazaquin
risk
assessments;
therefore,
the
aggregate
assessment
presented
here
should
be
considered
a
highly
conservative,
health­
protective,
screening
level
assessment.
If
estimates
of
dermal
exposure
were
excluded
from
the
aggregate
assessment,
estimated
aggregate
exposure
and
risk
for
both
children
and
adults,
while
already
below
HED's
level
of
concern,
would
be
even
lower.
The
following
table
summarizes
estimated
short­
term
aggregate
exposure
and
risk
based
on
inhalation
and
oral
routes
of
exposure
only:

Table
7.2c
Estimated
Short­
Term
Aggregate
Risk
excluding
Risk
from
Dermal
Exposure
NOAEL
mg/
kg/
day
Level
of
Concern1
Dietary
MOE2
Residential
Handler
MOE3
Residential
Postapplication
MOE4
Aggregate
MOE
(
Dietary
and
Residential)
5
Children,
1­
2
yrs.
old
25
100
24,400
N/
A
2,700
2,400
Adults,
50+
years
old
38,000
550,000
N/
A
35,700
1
Level
of
Concern
(
MOE)
based
on
10x
UF
for
interspecies
extrapolation
and
10x
UF
for
intraspecies
variation.
2
Dietary
MOE
=
NOAEL
(
25
mg/
kg/
day)
÷
Chronic
Dietary
exposure.
Dietary
exposure
from
Table
6.1.
3
Residential
Handler
MOE
(
inhalation
only),
based
on
liquid
application
to
turf
using
a
hose­
end
sprayer
(
the
scenario
with
the
highest
estimated
handler
exposure
­
see
Table
6.3.1.3).
4
Residential
Postapplication
MOE
for
Children
includes
oral
(
hand­
to­
mouth,
object­
to­
mouth
and
incidental
soil
ingestion)
short­
term
exposures
(
see
Table
6.3.2.3c).
5
Aggregate
MOE
calculated
using
the
following
formula:
1
÷
(
1/
MOEDietary
+
1/
MOEResidential
Handler
+
1/
MOEResidential
Postapplication)
=
Aggregate
MOE;
For
Children:
1
÷
(
1/
24,400
+
1/
2,700)
=
2,400;
For
Adults:
1
÷
(
1/
38,000
+
1/
550,000)
=
35,700.
Page
59
of
68
7.3
Intermediate­
Term
Aggregate
Risk
There
are
no
intermediate­
term
exposure
scenarios
for
imazaquin,
based
on
its
current
use
patterns.

7.4
Long­
Term
Aggregate
Risk
The
chronic
aggregate
risk
assessment
considered
exposures
from
food
and
water
only,
because
there
are
no
residential
uses
expected
to
contribute
to
chronic
exposures
for
this
chemical.
Since
water
exposure
was
incorporated
directly
into
the
DEEM­
FCID
dietary
exposure
analysis,
the
dietary
risk
estimates
reported
in
section
6.1
represent
the
total
chronic
aggregate
risk
for
imazaquin.
The
chronic
aggregate
risk
estimates
for
the
U.
S.
population
and
all
subgroups
are
<
1%
of
the
cPAD
and,
therefore,
below
HED's
level
of
concern.

7.5
Cancer
Risk
A
cancer
aggregate
risk
assessment
is
not
required,
since
there
was
no
evidence
of
carcinogenicity
in
the
toxicology
studies
submitted
for
imazaquin.

8.0
Cumulative
Risk
Characterization/
Assessment
Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
EPA
has
not
made
a
common
mechanism
of
toxicity
finding
as
to
imazaquin
and
any
other
substances
and
imazaquin
does
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
this
tolerance
action,
therefore,
EPA
has
not
assumed
that
has
a
common
mechanism
of
toxicity
with
other
substances.
For
information
regarding
EPA's
efforts
to
determine
which
chemicals
have
a
common
mechanism
of
toxicity
and
to
evaluate
the
cumulative
effects
of
such
chemicals,
see
the
policy
statements
released
by
EPA's
Office
of
Pesticide
Programs
concerning
common
mechanism
determinations
and
procedures
for
cumulating
effects
from
substances
found
to
have
a
common
mechanism
on
EPA's
website
at
http://
www.
epa.
gov/
pesticides/
cumulative/.

9.0
Occupational
Exposure/
Risk
Pathway
Since
this
risk
assessment
is
being
conducted
solely
for
tolerance
reassessment
purposes,
an
occupational
exposure
assessment
is
not
required.

10.0
Data
Needs
and
Label
Requirements
10.1
Toxicology
­
none
10.2
Residue
and
Product
Chemistry
Deficiencies
Page
60
of
68
Product
Chemistry
Deficiencies
Additional
data
are
required
concerning
product
identity,
certified
limits,
stability,
storage
stability,
and
UV/
visible
absorption
(
OPPTS
830.1550,
1750,
6313,
6317,
and
7050)
for
the
BASF
Corporation
imazaquin
95%
T
(
EPA
Reg.
No.
241­
287).

Additional
data
are
required
concerning
all
generic
product
chemistry
guidelines
(
OPPTS
830.1600,
1620,
1670,
1700,
6302,
6303,
6304,
6313,
7000,
7050,
7200,
7220,
7370,
7550,
7840,
xxxx
(
solvent
solubility,
formerly
63­
8),
and
7950)
for
the
BASF
Corporation
imazaquin
ammonium
salt
TGAI
and
Ambrands
imazaquin
ammonium
salt
TGAI.

Additional
data
are
required
concerning
all
generic
product
chemistry
guidelines
(
OPPTS
830.1600,
1620,
1670,
1700,
6302,
6303,
6304,
6313,
7000,
7050,
7200,
7220,
7370,
7550,
7840,
xxxx
(
solvent
solubility,
formerly
63­
8),
and
7950)
for
the
BASF
Corporation
imazaquin
sodium
salt
TGAI
Residue
Chemistry
Deficiencies
860.1380:
Storage
Stability
Data
/
860.1500:
Crop
Field
Trials
The
storage
duration
of
the
crop
field
trial
soybean
samples
from
harvest
to
analysis
was
not
provided
and
should
be
submitted.
Storage
stability
studies
indicate
that
residues
of
imazaquin
are
stable
on
soybeans
for
up
to
24
months
of
frozen
storage.
If
the
storage
duration
of
the
field
samples
was
greater
than
24
months,
storage
stability
information
should
be
submitted
to
cover
the
storage
duration.

860.1360:
Multiresidue
Method
Multiresidue
method
data
were
not
submitted.
The
registrant
should
submit
data
pertaining
to
the
recovery
of
imazaquin
via
FDA
Multiresidue
Protocols
(
PAM
Vol.
I).

10.3
Occupational
and
Residential
Exposure
­
none
References:

°
Imazaquin.
Tolerance
Reassessment
Eligibility
Decision
(
TRED).
Summary
of
Analytical
Chemistry
and
Residue
Data;
DP
Barcode
302944;
D.
Drew;
10/
6/
05.

°
Imazaquin.
Tolerance
Reassessment
Eligibility
Decision
(
TRED).
Product
Chemistry
Considerations;
DP
Barcode
302940;
D.
Drew;
10/
21/
05.
Page
61
of
68
°
Imazaquin
Chronic
Dietary
Exposure
Assessment
for
the
Reregistration
Eligibility
Decision,
DP
Barcode:
D302943,
Susan
Stanton,
10/
20/
05
°
Drinking
Water
Assessment
for
Imazaquin
and
its
Salts;
K.
Moore;
June
21,
2005,
as
amended
on
September
27,
2005.

°
Imazaquin:
Residential
Exposure
Assessment
and
Recommendations
for
the
Tolerance
Reassessment
Eligibility
Decision
(
TRED);
DP
Barcode:
D302942;
Seyed
Tadayon;
10/
06/
2005
°
Review
of
Imazaquin
Incident
Reports,
DP
Barcode:
D321563,
Jerome
Blondell,
10/
12/
2005
Page
62
of
68
Appendices
1.0
TOXICOLOGY
DATA
REQUIREMENTS
The
requirements
(
40
CFR
158.340)
for
food
use
for
imazaquin
are
presented
below.
Use
of
the
new
guideline
numbers
does
not
imply
that
the
new
(
1998)
guideline
protocols
were
used.

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
70.3100
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
No
yes
See
870.4100b
yes
N/
A
N/
A
870.3700a
Prenatal
Developmental
Toxicity
(
rat)
.
.
.
.
.
.
.
.
.
.
.
870.3700b
Prenatal
Developmental
Toxicity
(
rabbit)
.
.
.
.
.
.
.
.
.
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
See
870.4300
yes
See
870.4300
yes
yes
870.5100
Mutagenicity 
Gene
Mutation
­
bacterial
.
.
.
.
.
.
.
.
870.5300
Mutagenicity 
Gene
Mutation
­
mammalian
.
.
.
.
.
.
870.5375
Mutagenicity 
Structural
Chromosomal
Aberrations
870.5550
Mutagenicity 
Other
Genotoxic
Effects
.
.
.
.
.
.
.
.
.
.
yes
yes
yes
opt.
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
no
no
no
N/
A
N/
A
N/
A
N/
A
N/
A
870.7485
General
Metabolism
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
870.7600
Dermal
Penetration
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
yes
no
yes
N/
A
Special
Studies
for
Ocular
Effects
no
N/
A
N/
A
=
Not
Applicable
Page
63
of
68
2.0
ADDITIONAL
TOXICOLOGY
STUDIES
­
EXECUTIVE
SUMMARIES
870.3100.
Subchronic
Oral
Toxicity
in
the
Rat.

EXECUTIVE
SUMMARY:
In
a
subchronic
study
(
1983,
MRID
00131553),
CL
252,
214
(
88
%,
a.
i.,
imazaquin,
Lot
No.
AC
7207­
70B)
was
administered
to
30
male
and
30
female
Charles
River
CD
strain
albino
rats
per
group
at
concentrations
of
0,
250,
1000,
5000
or
10,000
ppm
for
13­
weeks.
The
average
CL
252,
214
intake
for
both
males
and
females
over
the
dosing
period
was
approximately
0,
20,
80,
400
and
800
mg/
kg/
day,
respectively.

No
mortalities
or
treatment­
related
clinical
signs
were
observed.
Average
weekly
food
intake
increased
significantly
(
p
<
0.05)
in
the
250
ppm
during
weeks
1,
3,
and
4
for
males
and
3­
6,
8,
11
and
13
for
females.
Females
were
also
observed
to
have
statistically
significant
increases
(
p
<
0.05)
in
food
intake
at
different
time­
points
(
not
specified)
in
the
1000
and
5000
ppm
groups.
All
other
dose
groups
were
comparable
to
controls.
Weight
gain
in
males
was
comparable
to
controls
in
all
dose
groups.
Treated
females
had
increased
weight
gain
throughout
the
study
but
this
was
only
statistically
significant
(
p
<
0.05)
in
the
5000
ppm
group.
No
statistically
significant
changes
were
observed
in
the
hematology,
urinalysis
or
chemical
chemistry
parameters.
Females
in
the
5000
ppm
group
had
statistically
significant
(
p
<
0.05)
increases
in
the
absolute
liver
and
kidney
weight;
however,
corresponding
relative
liver
and
kidney
weight
were
evident
and
no
corresponding
lesions
identified
on
gross
or
histopathological
examination.
T
LOAEL
for
Imazaquin)
can
not
be
determined.
The
NOAEL
was
10,000
ppm
(
800
mg/
kg/
day)
for
both
sexes
.

This
subchronic
toxicity
study
in
the
rat
is
Acceptable/
Guideline
and
satisfies
the
guideline
requirement
for
a
90­
day
oral
toxicity
study
(
OPPTS
870.3100;
OECD
408).

870.3200.
21­
Day
Dermal
Toxicity
in
Rabbits.

EXECUTIVE
SUMMARY:
In
a
21­
day
dermal
toxicity
study
(
1985,
MRID
00146204),
AC
252,
214
(
87.9%,
a.
i.,
Imazaquin
,
Lot
No.
AC
4325­
23)
was
applied
to
the
shaved
skin
of
six
New
Zealand
White
rabbits/
sex/
dose
at
concentrations
of
0,
250,
500
or
1000
mg/
kg
bw/
day,
6
hours/
day,
5
days/
week
for
three
consecutive
weeks.
Skin
in
three
rabbits
in
each
group
was
abraded
prior
to
treatment
and
three
were
left
intact.

Two
female
rabbits
died
during
the
study
(
one
high
and
one
mid
dose)
and
were
observed
to
have
an
ulcerative
enteritis,
not
considered
to
be
compound­
related.
There
were
no
differences
in
the
type
or
severity
of
clinical
signs
between
the
control
and
treated
animals.
No
significant
differences
were
observed
in
mean
body
weight.
Food
consumption
in
the
high­
dose
males
was
lower
than
controls
only
on
day
7.
The
white
blood
cell
(
WBC)
count
in
the
mid­
dose
females
was
statistically
significantly
lower
(
p#
0.05),
but
this
value
was
within
normal
range
of
historical
data
maintained.
No
toxicologically
significant
differences
were
observed
in
clinical
chemistry
values.
No
treatmentrelated
lesions
were
observed
on
gross
or
histopathological
examinations.
Two
male
rabbits
in
the
high­
dose
group
had
hypoplastic
seminiferous
tubules
in
the
testes
with
no
spermatogenesis.
There
was
no
difference
in
the
testicular
weight
and
the
finding
was
thought
to
be
from
testicular
Page
64
of
68
immaturity
and
not
compound­
related.
The
systemic
LOAEL
for
imazaquin
can
not
be
identified,
and
the
systemic
no­
observed­
adverse­
effect
level
(
NOAEL)
is
1000
mg/
kg
bw/
day.

The
only
dermal
irritation
was
slight
transient
erythema
observed
in
one
high­
dose
male
with
intact
skin
from
days
10­
17.
This
change
was
reported
normal
by
day
18.
Three
females
in
the
low­
dose
group
exhibited
very
slight
erythema
for
3­
4
days
intensifying
to
a
well­
defined
erythema
in
one
animal
although
it
was
not
stated
if
these
animals
had
intact
or
abraded
skin.
No
treatment­
related
dermal
irritation
was
observed
on
any
animal
on
gross
or
histopathological
examination.
The
dermal
LOAEL
imazaquin
in
rabbits
can
not
be
identified,
and
the
NOAEL
is
1000
mg/
kg
bw/
day.

This
21­
day
dermal
toxicity
study
in
rabbits
is
Acceptable/
Guideline.
It
satisfies
the
guideline
requirement
for
a
21/
28­
day
dermal
toxicity
study
(
OPPTS
870.3200;
OECD
410)
in
rabbits.
This
study
was
conducted
prior
to
the
implementation
of
the
current
guidelines.
The
skin
of
half
the
rabbits
was
abraded
but
since
no
systemic
effects
were
noted,
this
does
not
compromise
the
interpretation
of
the
study.

870.4200b.
Carcinogenicity
­
mice.

EXECUTIVE
SUMMARY:
In
carcinogenicity
study
(
1985,
MRID
00146206),
AC
252,214
(
Imazaquin,
87.9%
a.
i.,
Lot
No.
AC
4325­
23)
was
administered
in
the
diet
to
65
CD­
1
Albino
mice/
sex/
dose
at
concentrations
of
0,
250,
1000
or
4000
ppm
for
18
months.
Corresponding
concentrations
were
0,
38,
150,
or
600
mg/
kg
bw/
day,
respectively,
using
a
food
factor
of
0.15.
Ten
animals/
sex/
group
were
terminated
at
53
weeks
for
interim
evaluation.

No
treatment­
related
deaths
were
observed.
Occasional
clinical
signs
were
observed
but
were
either
considered
normal
for
caged
mice
or
transient.
Body
weight
was
significantly
(
p
<
0.05)
lower
in
the
high­
dose
females
throughout
the
study.
Body
weight
gain
in
the
high­
dose
females
was
also
lower
than
controls
starting
at
approximately
week
twelve
with
overall
weight
gain
decreased
by
19%
and
14%
in
the
first
year
and
the
entire
study,
respectively.
High­
dose
males
also
were
observed
to
have
some
time­
points
with
body
weight
that
was
significantly
lower.
Mean
body
weight
gain
in
high­
dose
males
was
decreased
by
13%
in
weeks
12­
24
and
31%
by
weeks
24­
42.
Weight
gain
was
6%
less
in
high­
dose
males
in
the
first
year,
but
was
similar
to
controls
for
the
entire
study.
No
treatment­
related
differences
in
food
consumption
were
observed.
No
treatmentrelated
changes
were
observed
in
the
hematology
parameters
measured.
In
high­
dose
females,
the
thyroid/
parathyroid
mean
absolute
weight
and
mean
organ­
to­
body
and
organ­
to­
brain
weight
ratio
were
increased
at
the
53
week
sacrifice.
However,
these
changes
were
not
observed
at
the
78­
week
sacrifice.
At
the
78
week
sacrifice,
high­
dose
males
had
a
significant
decrease
(
p
#
0.05)
in
mean
absolute
and
mean
organ­
to­
brain
weight
ratio
of
the
thyroid/
parathyroid
but
there
were
no
corresponding
histopathological
lesions.
Treated
females
in
all
dose
groups
had
decreased
mean
absolute
weight,
organ­
to­
brain
weight
and
organ­
to­
body
weight
of
the
pituitary
gland,
but
the
decreases
did
not
have
a
dose­
related
trend.
No
treatment­
related
lesions
were
identified
on
macroscopic
or
microscopic
examination
of
the
mice.
The
LOAEL
for
chronic
toxicity
Imazaquin
in
mice
is
4000
ppm
(
600
mg/
kg
bw/
day)
for
males
and
females
based
on
a
Page
65
of
68
treatment­
related
decrease
in
body
weight
and
body
weight
gain.
The
NOAEL
is
1000
ppm
(
150
mg/
kg
bw/
day)
for
males
and
females.

There
was
no
statistical
increase
in
the
incidence
of
neoplastic
lesions
in
male
or
female
mice
in
any
dose
group.
Dosing
appears
to
be
adequate
due
to
the
loss
in
body
weight
observed.

This
study
is
Acceptable/
Guideline
and
does
satisfy
the
guideline
requirement
for
a
chronic
toxicity/
carcinogenicity
study
in
mice.
[
OPPTS
870.4200b;
OECD
451].

870.4300.
Combined
Chronic
Feeding/
Carcinogenicity
­
rats.

EXECUTIVE
SUMMARY.
In
a
chronic
toxicity/
carcinogenicity
study
(
1985,
MRID
00156739),
AC
252,
214
(
89.4%,
a.
i.,
Imazaquin)
was
administered
in
feed
to
65
male
and
65
female
CDCrl
CD
(
SD)
BR
rats
per
group
at
concentrations
of
0,
1000,
5000
or
10,000
ppm
for
two
years.
Based
on
the
standard
food
factor
of
0.05
for
rats,
estimated
dietary
concentrations
resulted
in
doses
of
0,
50,
250,
or
500
mg/
kg
bw/
day,
respectively.
Five
animals/
sex/
group
were
sacrificed
at
six
months
and
10/
sex/
group
at
12
months.

Mortality
in
all
treated
groups
was
comparable
to
controls.
The
only
clinical
sign
observed
was
an
increase
in
the
number
of
animals
with
urine
staining
in
the
perineal
region
in
the
high­
dose.
This
was
observed
in
55
high­
dose
vs.
28
controls
in
the
males
and
42
high­
dose
vs.
25
controls
in
the
females.
However,
there
were
no
corresponding
effects
found
in
histopathological
examination
of
the
urogenital
tract.
Body
weight,
food
consumption,
hematology,
clinical
chemistry,
urinalysis,
organ
weight,
and
incidences
of
gross
and
histopathological
lesions
were
all
similar
between
control
and
treated
animals.
The
LOAEL
can
not
be
determined.
The
NOAEL
is
$
10,000
ppm
(
500
mg/
kg
bw/
day).

No
treatment­
related
increases
in
tumor
incidences
were
observed
in
either
sex
receiving
any
dose.
An
EPA
memo
(
1989)
was
attached
to
the
original
DER
for
this
study
with
the
following
statement:
"
This
study
was
conducted
at
doses
up
to
and
including
10,000
ppm.
Although
this
study
was
classified
as
supplementary
due
to
the
lack
of
toxicity
at
the
highest
dose,
an
additional
study
was
not
required
since
10,000
ppm
test
material
in
the
diet
was
considered
adequately
high
for
oncogenicity
testing.
Therefore,
this
study
is
now
classified
at
core­
minimum
and
an
additional
study
is
not
required."

This
chronic
toxicity/
carcinogenicity
study
in
the
rat
is
Acceptable/
Guideline
and
does
satisfy
the
requirements
for
a
combined
chronic/
carcinogenicity
study
[
OPPTS
870.4300
(
OECD
453)].

870.7485.
General
Metabolism
in
Rats.

EXECUTIVE
SUMMARY.
In
a
metabolism
study
(
1983,
MRID
00131547),
CL
252,214
(
radiopurity
99.54%;
19.42
µ
Ci/
mg;
Lot
No.
not
reported;
and
14C­
labeled
on
the
carboxylic
acid)
was
administered
by
gavage
to
two
groups
of
three
male
Sprague
Dawley
rats
at
a
concentration
of
12
mg/
kg.
A
fourth
rat
in
each
group
served
as
control.
Following
treatment,
the
rats
were
placed
individually
in
glass
metabolism
chambers
and
excreta
collected.
Twenty­
four
and
48
hours
after
Page
66
of
68
treatment,
three
treated
and
one
control
rat
were
sacrificed
and
blood,
liver,
kidney,
muscle,
and
fat
tissues
were
collected.

Approximately
101.9%
of
the
administered
radioactivity
was
recovered
within
48
hours
of
treatment.
The
majority
of
this,
94.28%,
was
recovered
in
the
urine
with
3.94%
recovered
in
the
feces,
and
3.75%
recovered
in
the
cage
wash.
Twenty­
four
hours
after
treatment,
residual
radioactivity
was
detected
in
the
liver
(
0.025
ppm)
and
kidney
(
0.17
ppm).
By
48
hours,
the
concentration
in
all
tissues
was
at
or
below
the
limit
of
detection
(
0.01
ppm).
Thin
layer
chromatography
of
urine
collected
24
and
48
hours
after
treatment
showed
that
of
the
radioactivity
recovered,
99.7%
was
unchanged
parent
compound.

This
study
does
not
follow
guideline
requirements
for
a
metabolism
study
in
the
rat.
However,
a
USEPA
memorandum
from
J.
E.
Harris
written
in
1986
states
in
part:
"
In
consideration
that
the
low
dose
metabolism
study
demonstrated
that
92
percent
of
the
administered
dose
(
12
mg/
kg
bwt)
was
excreted
as
unmetabolized
parent
compound
in
the
urine
at
24
hours
and
complete
excretion
occurred
within
48
hours,
there
appears
to
be
little
scientific
rationale
for
performing
additional
metabolism
studies,
with
multiple
doses,
or
a
high
dose.
Thus,
the
absence
of
metabolism
of
the
parent
compound
CL
252,214
or
Scepter
demonstrated
in
the
low
dose
metabolism
study
negates
the
requirement
for
additional
metabolism
studies."

Therefore,
this
metabolism
study
in
the
rat
is
classified
Acceptable/
Nonguideline
and
does
not
satisfy
guideline
requirement
for
a
metabolism
study
[
OPPTS
870.7485,
OECD
417]
in
the
rat.
Based
on
the
USEPA
memorandum
dated
March
18,
1986,
however,
the
data
requirements
for
a
metabolism
study
with
Imazaquin
have
been
satisfied.

Non­
Guideline
Special
Study
to
Assess
for
Thyroid
Function.

EXECUTIVE
SUMMARY:
In
an
oral
toxicity
study
to
investigate
the
effects
on
thyroid
function
(
1991,
MRID
42054601),
Imazaquin
(
AC
92,553)
(
a.
i.
92.6%
corrected
for
purity)
was
administered
to
male
Sprague
Dawley
rats
in
the
diet
for
up
to
92
days
at
concentrations
of
100
or
5000
ppm
(
equivalent
to
4.98
and
245.4
mg/
kg/
day,
respectively).
At
study
days
15,
29,
57,
and
92,
20
rats/
group
were
sacrificed
for
thyroid
function
studies.

Treatment
with
the
test
material
induced
a
slight
decrease
in
the
body
weight
of
5000
ppm
males,
however,
total
body
weight
gain
was
decreased
20%
over
the
course
of
the
study.
The
decrease
in
total
body
weight
gain
was
associated
with
a
commensurate
decrease
in
food
consumption.
No
significant
treatment­
related
effect
was
found
in
the
100
ppm
group.
Treatment
with
5000
ppm
test
material
induced
a
slight
increase
in
the
adjusted
TSH
of
male
rats
within
15
days
of
treatment.
(
The
TSH
data
set
was
adjusted
by
removing
results
>
1.5
sd
from
the
sample
mean.)
By
study
day
29,
the
adjusted
TSH
of
high­
dose
rats
was
double
that
of
controls,
before
decreasing
to
~
145%
of
control
by
study
days
57
and
92.
The
slight
increase
in
TSH
of
high­
dose
rats
was
accompanied
by
a
decrease
in
serum
total
T
4
.
The
total
T
4
of
high­
dose
rats
was
decreased
by
~
70%
from
day
15
through
the
remainder
of
the
study.
There
was
only
a
slight
effect
on
total
T
3
at
5000
ppm
and
no
significant
treatment­
related
effect
on
the
TSH,
T
3
and
T
4
of
100
ppm
rats.
The
absolute
and
Page
67
of
68
relative
thyroid
weight
of
5000
ppm
rats
was
increased
~
33%
by
day
15
and
through
the
remainder
of
the
study.
This
was
accompanied
with
minimal
to
moderate
thyroid
follicular
cell
hypertrophy.
No
increase
in
organ
weight
or
follicular
cell
hypertrophy
were
found
in
100
ppm
rats.
The
overall
thyroid
function
effects
observed
following
treatment
with
5000
ppm
AC
92,553
are
consistent
with
a
secondary
effect
on
the
thyroid
that
resulted
in
prolonged
stimulation
by
TSH.
Prolonged
lowgrade
stimulation
of
the
thyroid
by
TSH
is
a
known
mechanism
for
the
induction
of
thyroid
follicular
hypertrophy
with
eventual
progression
to
follicular
adenomas.
The
question
of
whether
the
follicular
hypertrophy
observed
in
this
study
was
a
direct
result
on
the
thyroid
or
increased
T
4
metabolism
is
unanswered.

This
92­
day
oral
toxicity
study
in
the
rat
is
Acceptable/
Nonguideline
and
satisfies
the
purpose
of
the
study.
Page
68
of
68
3.0
TOLERANCE
REASSESSMENT
FOR
IMAZAQUIN
The
tolerance
for
residues
of
imazaquin
in/
on
plant
commodities
is
expressed
in
terms
of
residues
of
imazaquin
per
se
2­[
4,5­
dihydro­
4­
methyl­
4­(
1­
methylethyl)­
5­
oxo­
1Himidazol­
2­
yl]­
3­
quinoline
carboxylic
acid.
A
summary
of
the
imazaquin
tolerance
reassessment
for
soybeans
is
presented
below.

Tolerances
Listed
Under
40
CFR
§
180.426:

A
tolerance
has
been
established
under
40
CFR
§
180.426
for
residues
of
imazaquin
in
or
on
soybeans.
Provided
that
the
deficiencies
cited
in
this
document
are
resolved,
HED
supports
the
current
tolerance
of
0.05
ppm.

The
Tolerance
Spreadsheet
developed
by
the
NAFTA
Tolerance/
MRL
Harmonization
Workgroup
was
not
used
to
determine
the
appropriate
tolerance
for
imazaquin
on
soybeans,
since
all
of
the
field
trial
residues
were
below
the
analytical
method's
Limit
of
Quantitation
(
LOQ).
The
reassessed
tolerance
is
set
at
the
LOQ
of
0.05
ppm.

Tolerance
Summary
for
Imazaquin
Commodity
Current
Tolerance
(
ppm)
Reassessed
Tolerance
(
ppm)
Comments
(
correct
commodity
definition)

Soybeans
0.05
0.05
Soybean,
seed
Codex/
International
Harmonization
There
are
no
Codex
or
Canadian
maximum
residue
limits
(
MRLs)
for
imazaquin.
Currently
in
Canada,
a
default
MRL
of
0.1
ppm
applies
when
specific
MRLs
have
not
been
established.
Based
on
this
consideration
and
the
fact
that
detectable
residues
of
imazaquin
are
not
expected
in
soybeans
from
its
current
U.
S.
uses,
the
lack
of
compatible
Codex
and
Canadian
MRLs
should
not
present
a
significant
trade
concern
for
U.
S.
growers.