Document ID: EPA-HQ-OPP-2005-0478-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2005-12-28T05:00Z

United
States
Prevention,
Pesticides
EPA
738­
R­
00­
009
Environmental
Protection
and
Toxic
Substances
December
2005
Agency
(
7508C)

Report
of
the
Food
Quality
Protection
Act
(
FQPA)
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
(
TRED)
for
Imazaquin
Report
of
the
Food
Quality
Protection
Act
(
FQPA)
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
(
TRED)
for
Imazaquin
Approved
By:

___________________________
Debra
Edwards,
Ph.
D.
Director,
Special
Review
and
Reregistration
Division
___________________________
Date
1
of
7
I.
Regulatory
Determination
The
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
as
amended
by
FQPA,
requires
EPA
to
reassess
all
the
tolerances
for
registered
chemicals
in
effect
on
the
day
before
enactment
of
the
FQPA
on
August
3,
1996.
In
reassessing
these
tolerances,
the
Agency
must
consider,
among
other
things,
aggregate
risks
from
non­
occupational
sources
of
pesticide
exposure,
whether
there
is
increased
susceptibility
to
infants
and
children,
and
the
cumulative
effects
of
pesticides
with
a
common
mechanism
of
toxicity.
When
a
safety
finding
has
been
made
that
aggregate
risks
are
not
of
concern,
the
tolerances
are
considered
reassessed.
Existing
tolerances
associated
with
imazaquin
must
be
reassessed
in
accordance
with
FFDCA,
as
amended
by
FQPA.
Ecological
and
occupational
assessments
were
originally
conducted
when
imazaquin
was
first
registered
in
1986.
Therefore,
no
further
ecological
or
occupational
assessments
were
conducted
as
part
of
this
Report
of
the
FQPA
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
for
Imazaquin
(
also
referred
to
as
a
TRED).

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
preplant
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.

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
the
Agency's
level
of
concern.
Estimated
aggregate
risk
Margin
of
Exposures
(
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
Agency
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.
In
making
this
determination,
EPA
has
considered
dietary
exposure
from
food
and
drinking
water
and
all
other
non­
occupational
sources
of
pesticide
exposure
for
which
there
is
reliable
information.
Therefore,
the
one
tolerance
established
for
residues
of
imazaquin
in
or
on
soybean
commodities
is
now
considered
reassessed
as
safe
under
section
408(
q)
of
FFDCA,
as
amended
by
FQPA.

The
Agency's
human
health
and
drinking
water
findings
for
the
pesticide
imazaquin
are
summarized
in
the
following
risk
assessments:
Imazaquin
and
its
Salts:
HED
Chapter
of
the
Tolerance
Reassessment
Eligibility
Decision
Document
(
TRED),
dated
October
31,
2005
and
2
of
7
Drinking
Water
Assessment
for
Imazaquin
and
its
Salts,
dated
June
21,
2005,
and
Amendment
to
Drinking
Water
Assessment
for
Imazaquin
and
its
Salts,
dated
September
27,
2005.
For
further
details,
please
refer
to
these
risk
assessments
and
other
technical
documents
pertaining
to
the
Imazaquin
TRED,
which
are
available
on
the
Internet
at
http://
www.
epa.
gov/
e­
dockets
and
in
the
public
docket
for
viewing.

The
Agency
is
issuing
this
TRED
document
for
imazaquin
as
announced
in
a
Notice
of
Availability
published
in
the
Federal
Register.
The
Agency
is
providing
a
30­
day
comment
period
for
stakeholders
to
respond
to
this
risk
management
decision.
If
substantive
information
is
received
during
the
comment
period
that
indicates
a
need
to
refine
any
of
EPA's
assumptions
or
a
need
for
risk
mitigation,
then
this
decision
will
be
modified
as
appropriate
through
an
amendment
to
the
TRED.

II.
Tolerance
Reassessment
A.
FQPA
Assessment
Supporting
Tolerance
Reassessment
Decision
The
Agency
has
conducted
risk
assessments
to
ensure
that
the
imazaquin
tolerances
meet
the
new
safety
standards
established
by
FFDCA,
as
amended
by
FQPA.
These
recent
risk
assessments
for
imazaquin
include
evaluation
of
potential
susceptibility
to
infants
and
children;
dietary,
drinking
water,
and
residential
exposure
of
adults
and
children;
and
aggregate
risk
from
these
various
exposure
pathways.

EPA
has
determined
that
risk
from
exposure
to
imazaquin
is
within
its
own
"
risk
cup."
In
other
words,
EPA
is
able
to
conclude
today
that
the
tolerance
for
imazaquin
meets
the
FQPA
safety
standards.
In
reaching
this
determination,
the
Agency
has
considered
the
available
information
on
the
potential
sensitivity
of
infants
and
children,
as
well
as
the
chronic
and
acute
food
exposure.
However,
an
endpoint
attributable
to
a
single
dose
was
not
identified
for
this
chemical;
therefore,
an
acute
reference
dose
(
RfD)
was
not
established
and
an
acute
dietary
assessment
was
not
conducted.
An
aggregate
assessment
was
conducted
for
exposures
through
food,
residential
uses,
and
drinking
water.
Results
of
this
aggregate
assessment
indicate
that
the
human
health
risks
from
these
combined
exposures
are
considered
to
be
within
acceptable
levels;
that
is,
combined
risks
from
all
exposures
to
imazaquin
"
fit"
within
the
individual
risk
cup
for
this
chemical.
The
Agency's
risk
assessment
conclusions
are
summarized
below.

FQPA
Safety
Factor
Considerations.
The
FFDCA,
as
amended
by
the
FQPA,
directs
the
Agency
to
use
an
additional
tenfold
(
10X)
safety
factor
to
take
into
account
potential
pre­
and
postnatal
toxicity
to
infants
and
children.
FFDCA
authorizes
the
Agency
to
modify
the
tenfold
safety
factor
only
if
reliable
data
demonstrates
that
the
resulting
level
of
exposure
would
be
safe
for
infants
and
children.

EPA
has
determined
that
imazaquin
does
not
cause
developmental
toxicity
in
rat
or
rabbit
fetuses
and
does
not
adversely
affect
reproductive
parameters
in
rats
in
a
three­
generation
study.
There
is
no
quantitative
or
qualitative
evidence
of
increased
susceptibility
of
rat
or
rabbit
fetuses
or
3
of
7
offspring
after
in
utero
and/
or
post­
natal
exposure
to
imazaquin
in
the
developmental
and
reproduction
studies.
In
addition,
dose­
response
relationships
are
well­
characterized
and
clear
No/
Lowest
Observable
Adverse
Effect
Levels
(
NOAELs/
LOAELs)
have
been
identified
for
the
critical
effects.
Therefore,
the
Special
FQPA
Safety
Factor
can
be
reduced
to
1X,
since
there
are
no
concerns
and
no
residual
uncertainties
for
pre­
and/
or
post­
natal
toxicity.

Further,
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.

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
four
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
longterm
duration.
An
acute
reference
dose
(
aRfD)
was
not
established,
since
an
endpoint
attributable
to
a
single
exposure
was
not
identified
from
the
available
database.

Dietary
Risks
from
Food
and
Drinking
Water.
Because
an
endpoint
attributable
to
a
single
dose
was
not
identified
from
the
available
toxicity
database
for
imazaquin,
an
acute
dietary
assessment
was
not
conducted.
A
chronic
dietary
risk
assessment
was
conducted
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.
The
Tier
1
chronic
analysis
assumed
100%
of
the
crop
treated
and
tolerance­
level
residues
for
all
foods.
Drinking
water
exposure
was
incorporated
directly
into
the
dietary
assessment
using
the
Tier
1
estimated
drinking
water
concentration
for
ground
water
generated
by
the
SCI­
GROW
model.

EPA's
Tier1
chronic
dietary
risk
assessment
indicates
that
dietary
risk
from
imazaquin
residues
in
food
and
drinking
water
is
low
and
not
of
concern.
The
resulting
chronic
dietary
exposure
estimates
using
the
DEEM­
FCID
model
were
less
than
1.0%
of
the
chronic
Population
Adjusted
Dose
(
cPAD)
for
the
U.
S.
general
population
and
all
population
subgroups.
Therefore,
no
mitigation
measures
are
necessary
to
address
dietary
risks
from
food
and
drinking
water.

Residential
Risks.
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
4
of
7
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).
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
tomouth
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.
Therefore,
no
mitigation
measures
are
necessary
to
address
residential
risks.

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.

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
results
of
the
deterministic,
Tier1
dietary
assessment
indicate
that
the
chronic
(
average)
dietary
exposure
to
imazaquin
from
food
and
water
is
well
below
the
Agency'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
(
average)
dietary
exposure
is
combined
with
short­
term
residential
exposure,
the
resulting
short­
term
aggregate
risk
estimates
for
adults
and
children
are
also
below
the
Agency'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.

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.
The
chronic
aggregate
risk
estimates
for
the
U.
S.
population
and
all
subgroups
are
<
1%
of
the
cPAD
and,
therefore,
below
the
Agency's
level
of
concern.

A
cancer
aggregate
risk
assessment
is
not
required,
since
there
was
no
evidence
of
carcinogenicity
in
the
toxicology
studies
for
imazaquin
In
sum,
therefore,
since
there
are
no
aggregate
risks
of
concern,
no
mitigation
measures
are
necessary
to
address
aggregate
risks.
5
of
7
B.
Cumulative
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
imazaquin
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/.

C.
Endocrine
Disruptor
Effects
EPA
is
required
under
the
FFDCA,
as
amended
by
FQPA,
to
develop
a
screening
program
to
determine
whether
certain
substances
(
including
all
pesticide
active
and
other
ingredients)
"
may
have
an
effect
in
humans
that
is
similar
to
an
effect
produced
by
a
naturally
occurring
estrogen,
or
other
such
endocrine
effects
as
the
Administrator
may
designate."
Following
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
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
decreases
in
thyroxine
(
T4)
and
tri­
iodothyronine
(
T3).
However,
the
dose
level
at
which
these
changes
were
noted
is
approximately
10­
fold
higher
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.

D.
Tolerance
Summary
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
6
of
7
quinoline
carboxylic
acid.
Imazaquin
has
one
tolerance
for
soybeans.
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
residue
and
product
chemistry
deficiencies
cited
in
Section
III
of
this
document
are
resolved,
the
Agency
supports
the
current
tolerance
of
0.05
ppm.
The
tolerance
is
set
at
the
Limit
of
Quantitation
(
LOQ)
of
the
analytical
method,
since
all
of
the
field
trial
residues
were
below
this
level.

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.

III.
Data
Gaps
and
Confirmatory
Data
Requirements
There
are
residue
and
product
chemistry
deficiencies
and
data
gaps
for
imazaquin.
These
data
are
not
expected
to
change
the
regulatory
conclusions
for
imazaquin
described
in
this
document.
The
following
is
the
list
of
the
required
data:

Product
Chemistry
°
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.
7
of
7
°
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
°
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).