Document ID: EPA-HQ-OPP-2004-0373-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2005-03-14T05:00Z

United
States
Prevention,
Pesticides
February
2005
Environmental
Protection
and
Toxic
Substances
Agency
(
7508C)

Report
of
the
Food
Quality
Protection
Act
(
FQPA)
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
(
TRED)
for
Imazamethabenzmethyl
2
UNITED
STATES
ENVIRONMENTAL
PROTECTION
AGENCY
WASHINGTON,
D.
C.
20460
OFFICE
OF
PREVENTION,
PESTICIDES
AND
TOXIC
SUBSTANCES
CERTIFIED
MAIL
Dear
Registrant:

This
is
the
Environmental
Protection
Agency's
(
hereafter
referred
to
as
EPA
or
the
Agency)
"
Report
of
the
Food
Quality
Protection
Act
(
FQPA)
Tolerance
Reassessment
Progress
and
Risk
Management
Decision
for
Imazamethabenz­
methyl,"
which
was
approved
February
28,
2005.
This
document
is
also
known
as
a
Tolerance
Reassessment
Decision,
or
TRED.
A
Notice
of
Availability
of
this
tolerance
reassessment
decision
will
be
published
shortly.

The
Federal
Food,
Drug
and
Cosmetic
Act
(
FFDCA),
as
amended
by
FQPA,
requires
EPA
to
reassess
all
the
tolerances
for
registered
chemicals
in
effect
on
or
before
the
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.
Once
a
safety
finding
has
been
made,
the
tolerances
are
considered
reassessed.
Existing
tolerances
and
exemptions
associated
with
imazamethabenz­
methyl
must
be
reassessed
in
accordance
with
FFDCA,
as
amended
by
FQPA.

The
Agency
has
evaluated
all
current
registered
uses
of
imazamethabenz­
methyl
and
has
determined
that
there
is
a
reasonable
certainty
that
no
harm
to
any
population
subgroup
will
result
from
exposure
to
imazamethabenz­
methyl
when
considering
dietary
exposure
and
all
other
nonoccupational
sources
of
pesticide
exposure
for
which
there
is
reliable
information.
Therefore,
no
mitigation
measures
are
needed
and
current
tolerances
at
40
CFR
§
180.437
for
imazamethabenzmethyl
are
now
considered
reassessed
under
section
408(
q)
of
the
FFDCA.
Tolerances
range
from
0.1
ppm
in/
on
barley
and
wheat
grain
and
sunflower
seeds
to
2.0
ppm
in/
on
barley
and
wheat
straw.
There
are
no
tolerances
for
residues
in
animal
commodities.

Imazamethabenz­
methyl
is
an
imidazolinone
herbicide
used
for
the
control
of
selected
annual
grass
and
broadleaf
weeds.
It
is
a
60:
40
mixture
of
two
isomers,
methyl
2­(
4­
isopropyl­
4­
methyl­
5­
oxo­
2­
imidazolin­
2­
yl)­
p­
toluate
[
para­
isomer]
and
methyl
6­(
4­
isopropyl­
4­
methyl­
5­
oxo­
2­
imidazolin­
2­
yl)­
m­
toluate
[
meta­
isomer].
In
the
United
States,
imazamethabenz­
methyl
is
registered
to
the
BASF
Corporation
and
is
formulated
as
a
2.5
lb/
gal
emulsifiable
concentrate
(
EC)
or
a
67%
3
water­
dispersable
granule
(
WDG)
for
a
single
early
postemergence
broadcast
application
to
barley,
wheat
or
sunflowers
using
ground
or
aerial
equipment.
The
use
on
sunflowers
is
restricted
to
several
Northern
Tier
States
(
MN,
ND,
and
SD),
and
the
use
on
barley
and
wheat
is
restricted
to
selected
states
west
of
the
Mississippi
River
(
CO,
ID,
MN,
ND,
OK,
OR,
SD,
TX,
UT,
WA,
and
WY).

Although
current
labels
prohibit
grazing
or
harvest
of
barley
hay
and
wheat
hay
treated
with
imazamethabenz­
methyl,
the
Agency
has
determined
that
these
types
of
restrictions
are
not
practical
and
that
tolerances
for
barley
hay
and
wheat
hay
should
be
established.
Therefore,
to
establish
these
new
tolerances,
residue
data
are
warranted
on
barley
hay
and
wheat
hay,
as
listed
below,
and
will
establish
appropriate
preharvest
intervals
(
PHIs).
Following
review
of
this
data,
labels
should
be
submitted
which
are
amended
to
include
PHIs
for
barley
hay
and
wheat
hay,
and
remove
the
restrictions
for
grazing
and
harvest
of
barley
hay
and
wheat
hay.

°
OPPTS
860.1500
 
Residue
data
are
required
on
barley
hay
(
12
test)
and
wheat
forage
hay
(
20
test).
The
tests
should
include
both
spring
and
winter
varieties
of
barley
and
wheat
and
should
be
conducted
in
states
where
the
use
of
imazamethabenz­
methyl
is
allowed.

°
OPPTS
860.1900
 
To
assess
the
need
for
tolerances
for
inadvertent
residues
in
rotated
crops,
the
registrant
should
conduct
limited
field
accumulation
studies
for
rotational
crops
in
accordance
with
current
Agency
guidance.
At
two
test
sites,
a
representative
leafy
vegetable,
cereal
grain,
and
root
vegetable
should
be
planted
the
year
following
an
application
of
imazamethabenz­
methyl
to
a
primary
crop
of
wheat
or
barley
at
the
maximum
labeled
use
rate
(
0.47
lb
ai/
A).

The
need
for
a
cattle
feeding
study
will
be
reserved
pending
review
of
the
requested
residue
data
on
forage
and
hay.
Note
that
a
complete
data
call­
in
(
DCI),
with
all
pertinent
instructions,
will
be
sent
to
the
registrant
under
separate
cover.

Tolerances
should
be
recodified
in
40
CFR
§
180.437
creating
paragraph
headings
(
a),
(
b),
(
c),
and
(
d)
as
follows:

°
heading
(
a)
General:
reserved
°
heading
(
b)
Section
18
emergency
exemptions:
reserved
°
heading
(
c)
Tolerances
with
regional
restrictions:
insert
existing
tolerances
°
heading
(
d)
Indirect
or
inadvertent
residues:
reserved.

Minimal
toxicity,
and
only
at
high
doses,
occurred
in
the
different
imazamethabenz­
methyl
toxicity
studies.
The
rat
and
mouse
oncogenicity
studies
were
negative
for
carcinogenic
effects.
Imazamethabenz­
methyl
is
classified
as
not
likely
to
be
carcinogenic.
Imazamethabenz­
methyl
4
showed
no
developmental
or
reproductive
effects
in
rats
and
developmental
effects
in
rabbits
only
at
high
doses.
Neurotoxicity
was
not
observed
in
any
of
the
toxicity
studies.

For
acute
dietary,
a
rabbit
developmental
toxicity
study
with
a
No
Observable
Adverse
Effect
Level
(
NOAEL)
of
500
mg/
kg/
day
and
a
Lowest
Observed
Adverse
Effect
Dose
(
LOAEL)
of
750
mg/
kg/
day
was
used.
An
Uncertainty
Factor
of
100
(
10X
for
interspecies
extrapolation
and
10X
for
intraspecies
variations)
was
applied
by
dividing
the
NOAEL
by
100.
The
acute
reference
dose
(
RfD)
is
therefore
5
mg/
kg/
day.
The
developmental
rabbit
study
was
selected
for
the
acute
dietary
(
females
13­
49
years
old)
exposure
scenario.

For
the
chronic
dietary
risk
assessment,
a
chronic
dog
feeding
study
with
a
No
Observable
Adverse
Effect
Level
(
NOAEL)
of
25
mg/
kg/
day
and
a
Lowest
Observed
Adverse
Effect
Dose
(
LOAEL)
of
100
mg/
kg/
day
was
used.
An
Uncertainty
Factor
of
100
(
10X
for
interspecies
extrapolation
and
10X
for
intraspecies
variations)
was
applied
by
dividing
the
NOAEL
by
100.
The
chronic
RfD
is
therefore
0.25
mg/
kg/
day.

EPA
calculated
Population
Adjusted
Doses
(
PADs),
which
are
the
RfDs
divided
by
the
FQPA
safety
factors.
Based
on
the
hazard
data,
the
special
FQPA
SF
is
1X
because
there
are
no/
low
concerns
and
no
residual
uncertainties
with
regard
to
pre­
and/
or
postnatal
toxicity.
Therefore,
the
PAD
is
numerically
equal
to
the
RfD.
The
RfD
and
PAD
for
acute
effects
is
5.0
mg/
kg/
day.
The
PAD
for
chronic
effects
(
general
population
and
all
population
subgroups)
is
also
equal
to
the
chronic
reference
dose
of
0.25
mg/
kg/
day.

A
Tier
I
dietary
exposure
assessment
for
food
only
was
performed
using
modeling.
The
assumptions
of
these
dietary
exposure
assessments
were
tolerance
level
residues
and
100%
crop
treated.
The
dietary
exposure
analyses
in
this
assessment
for
imazamethabenz­
methyl
resulted
in
dietary
risk
estimates
for
food
that
were
below
the
Agency's
level
of
concern
for
acute
and
chronic
dietary
exposure.
Both
the
acute
and
chronic
exposures
were
<
1%
of
the
PAD.
Potential
drinking
water
concentration
for
the
acute
and
chronic
assessments
were
estimated
using
modeling.
The
most
conservative
numbers
were
used
in
this
risk
assessment,
which
included
imazamethabenz­
methyl
(
para
and
meta­
isomer
of
methyl
parent)
and
their
respective
acid
metabolites.

Because
this
is
a
TRED,
occupational
handler
and
post
application
scenarios
were
not
assessed.
Furthermore,
there
are
no
residential
uses
for
imazamethabenz­
methyl;
it
is
only
registered
for
a
single,
early
season,
postemergence
application
to
wheat,
barley,
and
sunflowers.

As
there
are
no
residential
uses,
the
aggregate
exposure
assessment
for
imazamethabenzmethyl
consists
of
food
and
drinking
water
only.
The
most
conservative
water
concentration
estimates
were
selected
for
both
the
acute
and
chronic
dietary
assessment
and
implemented
into
the
Tier
1
dietary
assessment.
The
aggregate
risk
analysis
for
imazamethabenz­
methyl
results
in
dietary
risk
estimates
for
food
and
water
that
are
not
of
concern
to
the
Agency.
5
The
nature
of
the
residue
in
plants
is
adequately
understood
based
on
metabolism
studies
with
sunflower
and
wheat.
Although
information
is
limited
on
imazamethabenz­
methyl
metabolism
in
livestock,
the
Agency
concluded
that
the
available
ruminant
and
poultry
metabolism
studies
are
sufficient
to
support
the
current
uses
on
barley,
wheat,
and
sunflower.
The
residues
of
concern
for
tolerance
enforcement
and
risk
assessment
are
the
para­
and
meta­
isomers
of
the
parent
methyl
ester
along
with
their
respective
acid
metabolites,
2­(
4­
isopropyl­
4­
methyl­
5­
oxo­
2­
imidazolin­
2­
yl)­
p­
toluic
acid
(
CL
252,768)
and
6­(
4­
isopropyl­
4­
methyl­
5­
oxo­
2­
imidazolin­
2­
yl)­
m­
toluic
acid
(
CL
222,575).
Five
tolerances
for
barley
and
wheat
scenarios
are
established
under
40
CFR
§
180.437.
There
are
no
tolerances
established
for
imazamethabenz­
methyl
residues
in
livestock
tissues,
milk
or
eggs
as
the
Agency
has
concluded
that
there
is
no
reasonable
expectation
of
finite
residues
(
40
CFR
§
180.6(
a)(
3))
of
imazamethabenz­
methyl
in
livestock
commodities
based
on
the
current
registered
uses
in
or
on
livestock
feed
commodities
that
might
result
in
imazamethabenz­
methyl
residues.
Therefore,
the
five
existing
tolerances
for
imazamethabenz­
methyl
are
considered
reassessed
under
Section
408(
q)
of
the
FFDCA.

FQPA
requires
that
EPA
consider
"
available
information"
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
"
other
substances
that
have
a
common
mechanism
of
toxicity."
The
Agency
considers
other
substances
because
low­
level
exposures
to
multiple
chemical
substances
that
cause
a
common
toxic
effect
by
a
common
mechanism
could
lead
to
the
same
adverse
health
effect,
as
would
a
higher
level
of
exposure
to
any
of
the
other
substances
individually.

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
imazamethabenz­
methyl
and
any
other
substances
and
imazamethabenz­
methyl
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
imazamethabenz­
methyl
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/.

Based
on
currently
available
data,
imazamethabenz­
methyl
does
not
appear
to
be
an
endocrine
disruptor.
However,
when
the
appropriate
screening
and/
or
testing
protocols
being
considered
under
the
Agency's
Endocrine
Disruptor
Screening
Program
have
been
developed,
imazamethabenz­
methyl
may
be
subjected
to
additional
screening
and/
or
testing
to
better
characterize
effects
related
to
endocrine
disruption.
6
This
document
summarizes
the
Agency's
decision
on
the
tolerance
reassessment
for
imazamethabenz­
methyl.
Please
contact
Craig
Doty
of
my
staff
with
any
questions
regarding
this
decision.
He
may
be
reached
by
phone
at
(
703)
308­
0112
or
by
e­
mail
at
doty.
craig@
epa.
gov.

Sincerely,

Debra
Edwards,
Ph.
D.
Director
Special
Review
and
Reregistration
Division
Enclosures:
1.
Imazamethabenz:
Tier
1Acute
and
Chronic
Dietary
Exposure
Assessment
for
the
Reregistration
Eligibility
Decision.
2.
Imazamethabenz­
methyl:
HED
Chapter
of
the
Tolerance
Reassessment
Eligibility
Document
(
TRED).
3.
Environmental
Fate
and
Effects
Division's
FQPA
Drinking
Water
Assessment
for
Imazamethabenz
4.
Environmental
Fate
and
Effects
Division's
Review
of
the
Soil
Metabolism
Study
for
Imazamethabenz