Document ID: EPA-HQ-OPP-2006-0292-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-04-21T04:00Z

FILE
NAME:
company.
wpt
(
7/
1/
2005)
(
xml)
Template
Number
P25
ATTENTION:

All
commodity
terms
must
comply
with
the
Food
and
Feed
Commodity
Vocabulary
database
(
http://
www.
epa.
gov/
pesticides/
foodfeed/).

All
text
in
blue
font
(
instructions
for
preparing
the
document),
should
be
removed
prior
to
sending
the
document
to
the
Federal
Register
Staff.
Instructional
text
and
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font
should
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be
removed.

COMPANY
FEDERAL
REGISTER
DOCUMENT
SUBMISSION
TEMPLATE
(
1/
1/
2005)

EPA
Registration
Division
contact:
[
Ms.
Joanne
Miller,
703­
305­
6224
and
Ms.
Barbara
Madden,
703­
308­
6463]

TEMPLATE:

[
Interregional
Research
Project
No.
4
(
IR­
4)
in
cooperation
with
Syngenta
Crop
Protection,
Inc.]

[
petition
number
for
new
crops]

EPA
has
received
a
pesticide
petition
([
requesting
the
establishment
of
tolerances
for
Smetolachlor
from
[
Interregional
Research
Project
No.
4
(
IR­
4)
in
cooperation
with
Syngenta
Crop
Protection,
Inc.],
[
New
Jersery
Agricultural
Experiment
Station,
P.
O.
Box
231
Rutgers
University,
New
Brunswick,
NJ
08903
and
410
Swing
Rd.,
Greensboro,
NC
27419]
proposing,
pursuant
to
section
408(
d)
of
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
FFDCA),
21
U.
S.
C.
346a(
d),
to
amend
40
CFR
part
180.

1.
by
establishing
a
tolerance
for
residues
of
2.
to
establish
an
exemption
from
the
requirement
of
a
tolerance
for
[[
S­
metolachlor
[
Acetamide,
2­
chloro­
N­(
2­
ethyl­
6­
methylphenyl)­
N­(
2­
methoxy­
1­
methylethyl)­,
(
S)]
(
CAS
Number
87392­
12­
9)
and
its
metabolites,
determined
as
the
derivatives,
2­[(
2­
ethyl­
6­
methylphenyl)
amino]­
1­
propanol
and
4­(
2­
ethyl­
6­
methylphenyl)­
2­
hydroxy­
5­
methyl­
3­
morpholinone,
each
expressed
as
the
parent
compound
under
40
CFR
§
180.368(
a)(
2)
­
(
d)(
2)]
in
or
on
the
raw
agricultural
commodity
[
pumpkin
and
winter
squash],
at
[
0.1]
parts
per
million
(
ppm).
EPA
has
determined
that
the
petition
contains
data
or
information
regarding
the
elements
set
2
forth
in
section
408(
d)(
2)
of
the
FFDCA;
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
supports
granting
of
the
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.

A.
Residue
Chemistry
1.
Plant
metabolism.
[
The
qualitative
nature
of
S­
metolachlor
residues
in
plants
is
adequately
understood
based
upon
available
EPA
approved
corn,
potato,
and
soybean
metabolism
studies.
The
metabolism
of
S­
metolachlor
involves
conjugation
with
glutathione,
breakage
of
this
bond
to
form
the
mercaptan,
conjugation
of
the
mercaptan
with
glucuronic
acid,
hydrolysis
of
the
methyl
ether,
and
conjugation
of
the
resultant
alcohol
with
a
neutral
sugar.
EPA
has
determined
that
residues
of
concern
in
plants
include
parent
and
metabolites,
determined
as
the
derivatives
CGA­
37913
and
CGA­
49751.]

2.
Analytical
method.
[
The
Pesticide
Analytical
Manual
(
PAM)
Vol.
II,
Pesticide
Regulation
Section
180.368
lists
a
GC/
NPD
method
(
Method
1)
for
determining
residues
in
/
on
plants
and
a
GC/
MSD
method
for
determining
residues
in
livestock
commodities.
These
methods
determine
residues
of
S­
metolachlor
and
its
metabolites
as
either
CGA­
37913
or
CGA­
49751
following
acid
hydrolysis.
The
limit
of
quantitation
(
LOQ)
for
the
method
is
0.03
ppm
for
CGA­
37913
and
0.05
ppm
for
CGA­
49751.
Syngenta
has
also
developed
a
chiral
specific
analytical
method
to
allow
for
the
determination
of
residues
that
are
specific
to
S­
metolachlor.
It
is
this
chiral
specific
method
that
Syngenta
and
IR­
4
proposes
for
future
use
as
the
analytical
enforcement
method
in
support
of
these
requested
tolerances.
Syngenta
No.
1848­
01
was
used
in
several
of
the
studies
in
this
petition
to
analyze
agricultural
commodities.
The
latter
chiral
specific
method
is
the
same
as
the
updated
tolerance
enforcement
method,
except
that
chiral
chromatography
and
LC/
MS/
MS
are
used
to
separate
and
quantitate
the
hydrolysis
products
SYN506357
(
s­
configured
enantiomer
of
CGA­
37913)
and
SYN508500
(
s­
configured
enantiomer
of
CGA­
49751).]

3.
Magnitude
of
residues.
[
Winter
Squash:
Eleven
magnitude
of
residue
trials
were
conducted
under
the
direction
of
IR­
4
in
NAFTA
Region
1
(
NY,
one
trial),
Region
1A
(
Nova
Scotia,
one
trial)
Region
2
(
GA
&
NJ,
two
trials),
Region
3
(
FL,
one
trial),
Region
5
(
WI,
one
trial;
ON,
two
trials),
Region
5B
(
Quebec,
one
trial),
Region
10
(
CA,
one
trial),
and
Region
12
(
British
Columbia,
one
trial)
on
winter
squash.
Applications
were
made
preemergence
and
early
postemergence
and
fruit
were
harvested
at
normal
maturity
ranging
from
31­
105
days
after
application.
Total
maximum
residues
in
winter
squash
from
preemergence
applications
was
<
0.08
ppm.
Total
maximum
residues
in
winter
squash
from
postemergence
applications
was
<
0.08
ppm
with
a
single
exception
occurring
at
0.1
ppm.

[
Pumpkin:
Magnitude
of
residue
trials
were
conducted
on
winter
squash
as
a
representative
3
commodity
in
support
of
the
cucurbit
vegetable
crop
group
subgroup
9­
B
of
which
pumpkin
is
included.
]

B.
Toxicological
Profile
1.
Acute
toxicity.
[
The
data
base
for
acute
toxicity
for
S­
metolachlor
is
complete.
Smetolachlor
is
moderately
acutely
toxic
(
Toxicity
Category
III)
by
the
oral
and
dermal
route
and
relatively
non­
toxic
(
Toxicity
category
IV)
by
the
inhalation
route.
It
causes
slight
eye
irritation
(
Toxicity
Category
III)
and
is
non­
irritating
dermally
(
Toxicity
Category
IV);
the
active
ingredient
was
found
to
be
positive
in
a
dermal
sensitization
test
but
this
effect
is
mitigated
in
end­
use
product
formulations.]

2.
Genotoxicty.
[
The
data
base
for
S­
metolachlor
has
been
deemed
to
be
adequate
by
EPA.
Gene
mutation
studies
(
Guideline
870.5100),
micronucleus
(
Guideline
870.5395),
and
unscheduled
DNA
synthesis
(
Guideline
870.5550)
studies
have
recently
been
reviewed
and
approved
by
EPA.
There
is
no
evidence
of
a
mutagenic
or
cytogentic
effect
in
vivo
or
in
vitro
with
S­
metolachlor.]

3.
Reproductive
and
developmental
toxicity.
[
The
data
base
for
developmental
and
reproductive
toxicity
for
S­
metolachlor
are
considered
complete
according
to
EPA
reviews.
The
prenatal
developmental
studies
in
the
rat
and
rabbit
with
S­
metolachlor
revealed
no
evidence
of
a
qualitative
or
quantitative
susceptibility
in
fetal
animals.
No
significant
developmental
toxicity
was
observed
in
most
studies
even
at
the
highest
does
tested.
In
a
twogeneration
reproduction
study,
there
was
no
evidence
of
parental
or
reproductive
toxicity
at
the
highest
dose
tested
(
80
mg/
kg/
day).
The
results
indicate
that
S­
metolachlor
is
not
embryotoxic
or
teratogenic
in
either
species
at
maternally
toxic
doses.]

4.
Subchronic
toxicity.
[
In
a
90­
day
dietary
study
in
rats
with
S­
metolachlor,
no
effects
were
observed
in
male
or
females
at
208
and
236
mg/
kg/
day,
respectively.
In
another
90­
day
dietary
study
in
rats,
decreased
body
weight,
reduced
food
consumption
and
food
efficiency
in
both
sexes
and
increased
kidney
weight
in
males
at
150
mg/
kg/
day;
the
NOAEL
was
15
mg/
kg/
day.
A
90­
day
dog
study
with
S­
metolachlor
in
dogs
has
been
accepted
by
EPA;
no
effects
were
observed
in
males
and
females
at
62
mg/
kg/
day
and
74
mg/
kg/
day,
respectively,
the
highest
doses
tested.]

5.
Chronic
toxicity.
[
The
data
base
that
supports
S­
metolachlor
is
considered
adequate
4
by
EPA.
A
combined
chronic
toxicity
/
carcinogenic
study
in
the
rat
satisfies
the
requirements
for
both
the
chronic
toxicity
and
carcinogenicity
studies.
No
significant
chronic
toxicity
was
found
in
either
rats
or
dogs.
In
the
rat,
a
decrease
in
body
weight
was
observed
at
the
highest
dose
tested.
In
the
chronic
dog
study
that
supports
S­
metolachlor,
the
only
adverse
effect
was
decreased
body
weight
gain
in
females
at
33
mg/
kg/
day;
the
NOAEL
was
10
mg/
kg/
day.]

6.
Animal
metabolism.
[
The
data
base
for
S­
metolachlor
is
considered
to
be
complete.
In
animals,
S­
metolachlor
is
extensively
absorbed,
rapidly
metabolized
and
almost
totally
eliminated
in
the
excreta
of
rats,
goats,
and
poultry.
Metabolism
in
animals
proceeds
through
common
Phase
1
intermediates
and
glutathione
conjugation.]

7.
Metabolite
toxicology.
[
The
metabolism
of
S­
metolachlor
has
been
well
characterized
in
standard
FIFRA
metabolism
studies.
S­
metolachlor
does
not
readily
undergo
dealkylation
to
form
an
aniline
or
quinone
imine
as
has
been
reported
for
other
members
of
the
chloroacetanilide
class
of
chemicals.
Therefore,
as
EPA
has
agreed,
it
is
not
appropriate
to
include
S­
metolachlor
with
the
group
of
chloroacetanilides
that
readily
undergo
dealkylation,
producing
a
common
toxic
metabolite
(
quinone
imine).
EPA
has
recently
reviewed
new
toxicology
data
submitted
by
Syngenta
demonstrating
that
the
S­
metolachlor
metabolites
ethane
sulfonic
acid
(
CGA
354743)
and
oxanilic
acid
(
CGA
51202)
are
not
absorbed
by
mammalian
systems
and
/
or
have
a
significantly
lower
level
of
mammalian
toxicity
when
compared
to
parent.]

8.
Endocrine
disruption.
[
S­
Metolachlor
does
not
belong
to
a
class
of
chemicals
known
or
suspected
of
having
adverse
effects
on
the
endocrine
system.
There
is
no
evidence
that
S­
metolachlor
has
any
effect
on
endocrine
function
in
developmental
or
reproduction
studies.
Furthermore,
histological
investigation
of
endocrine
organs
in
the
chronic
dog,
rat
and
mouse
studies
did
not
indicate
that
the
endocrine
system
is
targeted
by
S­
metolachlor,
even
at
maximally
tolerated
doses
administered
for
a
lifetime.
There
is
no
evidence
that
S­
metolachlor
bioaccumulates
in
the
environment.]

C.
Aggregate
Exposure
1.
Dietary
exposure.
[
A
Tier
III/
IV
chronic
dietary
exposure
analysis
was
conducted
on
S­
metolachlor
using
field
trial
and
market
basket
survey
residues.
Field
trial
residues
were
adjusted
for
percent
of
crop
treated
whereas
market
basket
residues
were
not,
since
this
information
is
inherent
in
the
data.
The
percent
of
crop
treated
was
assumed
to
be
100%
for
5
all
commodities
for
which
no
percent
of
crop
treated
information
was
available.
The
chronic
assessment
was
conducted
for
S­
metolachlor
using
the
Dietary
Exposure
Evaluation
Model
(
DEEMTM,
version
7.76)
by
Exponent
and
food
consumption
information
from
USDA's
1994­
96
Continuing
Survey
of
Food
Intake
by
Individuals
(
CSFII)
and
the
Supplemental
CSFII
children's
survey
(
1998).
For
this
chronic
assessment,
the
field
trial
values
were
averaged
and
entered
into
the
DEEMTM
software.
Syngenta
Market
Basket
Survey
(
SMBS)
S­
metolachlor
data
were
available
for
the
following
commodities:
milk,
potatoes
and
tomatoes.
The
Syngenta
market
basket
survey
was
conducted
from
September
1999
through
September
2000.
Following
the
Agency
tier
ranking
system,
these
chronic
dietary
assessments
are
considered
as
Tier
III
(
utilizing
field
trial
data)
and
Tier
IV
(
utilizing
SMBS
and
PDP
data)
assessments.

S­
metolachlor
is
not
considered
acutely
toxic
and
therefore
acute
dietary
exposure
was
not
determined;
however,
in
the
October
2002
TRED
EPA
conducted
an
acute
assessment
of
the
majority
of
the
crops
currently
approved
and
determined
acute
risks
to
be
<
1%
of
the
aPAD
in
the
most
exposed
population
subgroup.

The
chronic
RfD
for
S­
metolachlor
is
0.10
mg/
kg
body
weight/
day
and
is
based
on
a
one­
year
dog
study
with
a
NOEL
of
9.7
mg/
kg
body
weight/
day
and
a
safety
factor
of
100X.
EPA
has
confirmed
in
the
October
2002
TRED
that
this
is
the
correct
reference
dose
and
that
no
additional
FQPA
safety
factor
is
required;
therefore,
additional
safety
factors
were
not
applied
in
this
assessment.
]

i.
Food.
[
The
risk
from
chronic
dietary
exposure
to
S­
metolachlor
is
considered
to
be
very
low.
The
%
of
the
chronic
RfD
ranged
from
0.2%
for
50
years
old
and
older
to
0.5%
for
Children
1­
2
years
old,
theoretically
the
most
exposure
population
subgroup.]

ii.
Drinking
water.
[
Other
potential
sources
of
exposure
of
the
general
population
to
residues
of
S­
metolachlor
are
residues
in
drinking
water
and
exposure
from
non­
occupational
sources.
The
degradation
of
S­
metolachlor
is
microbially
mediated
with
an
aerobic
soil
metabolism
primary
halflife
of
less
than
30
days
and
subsequently
soil
binding
predominates.
S­
metolachlor
Koc's
vary
from
110­
369.
S­
metolachlor
is
stable
to
hydrolysis
and
while
aqueous
and
soil
photolysis
occur,
they
are
not
expected
to
be
prominent
pathways
in
the
environment.
The
predominant
crop
for
S­
metolachlor
is
corn
and
accordingly
an
Index
Reservoir
PRZM/
EXAMS
was
run
using
EPA's
standard
corn
scenario.
The
model
simulated
two
applications
to
the
same
plot:
pre­
emergence
(
2.67
kg
ai/
ha)
and
post­
emergence
(
1.50
kg
a.
i./
ha).
The
mean
annual
average
EEC
was
11.77
ppb.
It
should
be
noted
that
extensive
monitoring
data
suggests
that
this
EEC
is
a
conservative
estimate.
For
the
vast
majority
of
locations
sampled,
the
peak
measured
concentration
does
not
approach
12
ppb,
and
the
annual
average
would
be
expected
to
be
much
lower.

The
Chronic
DWLOC
was
calculated
based
on
a
cRfD
of
0.097
mg/
kg/
day.
Children
1
­
2
years
old
are
the
most
sensitive
subpopulation
and
their
DWLOC
is
estimated
to
be
544
ppb
which
corresponds
to
a
%
cRfD
value
of
2.2%
with
an
MOE
value
of
4621.
Thus,
the
DWLOC
is
6
considerably
higher
than
the
EEC
of
11.77
ppb
and
the
MOE
is
well
above
the
benchmark
value
of
100.
Again,
the
October
2002
TRED
published
by
EPA
for
public
comment
that
included
the
majority
of
the
uses
requested
in
this
petition
confirmed
the
low
level
of
exposure
to
S­
metolachlor
in
drinking
water.]

2.
Non­
dietary
exposure
.
[
S­
metolachlor
is
labeled
for
use
on
warm­
season
turf
and
landscape
ornamentals.
Although
it
is
primarily
used
on
sod
farms
and
commercial
landscape
ornamentals,
it
can
be
used
by
licensed
pest
control
operators
(
PCO)
or
lawn
care
operators
(
LCO)
on
residential
turf.
Since
S­
metolachlor
can
only
be
applied
to
warm­
season
turf
varieties
(
bermudagrass,
Zoysiagrass,
St.
Augustinegrass,
and
Centipedegrass),
its
use
on
turf
is
limited
to
the
southern
states.

Non­
dietary
residential
exposure
may
occur
to
homeowners
or
children
as
a
result
of
exposure
during
re­
entry
activities.
Using
surrogate
dislodgeable
foliar
residue
data,
and
conservative
standard
EPA
exposure
scenarios,
exposure
through
the
dermal
route
was
calculated.
Based
on
the
use
pattern,
which
restricts
to
number
of
application
to
one
per
year,
only
short­
term
risks
need
to
be
considered.
The
relevant
toxicological
endpoint
for
short­
term
dermal
risks
is
the
NOEL
of
100
mg/
kg/
day
from
a
21­
day
dermal
toxicity
study
in
rabbits.
No
acute
oral
hazard
has
been
identified
following
an
acute
exposure
to
S­
metolachlor
and,
therefore,
no
nondietary
assessment
is
needed.

The
short­
term
dermal
post­
application
risks
for
adults
and
children
are
acceptable,
ranging
from
520
to
870.
These
risk
estimates
exceed
the
EPA's
level
of
concern
for
S­
metolachlor
(
all
MOEs
are
greater
than
100).

Aggregate
Exposure
(
Drinking
Water
and
Dietary
Exposure)
Using
the
Total
MOE
equation
for
the
determination
of
aggregate
chronic
exposure
(
food
and
drinking
water
only)
resulted
in
an
aggregate
MOET
of
>
4,000.
for
the
most
sensitive
subpopulation,
non­
nursing
infants.
For
this
particular
subpopulation,
there
are
no
non­
dietary
exposure
contributions
to
the
MOET
aggregate
value.
]

D.
Cumulative
Effects
[
EPA
has
examined
the
common
mechanism
potential
for
S­
metolachlor
and
has
concluded
that
S­
metolachlor
should
not
be
included
with
some
pesticides
that
comprise
the
class
of
chloroacetanilides
included
in
a
"
Common
Mechanism
Group".
Therefore,
a
cumulative
assessment
is
not
necessary
for
S­
metolachlor.]

E.
Safety
Determination
1.
U.
S.
population.
[
Based
on
the
aggregate
assessment
described
above
and
the
completeness
and
reliability
of
the
toxicity
data,
it
is
concluded
that
aggregate
exposure
to
S­
metolachlor
(
including
the
proposed
uses)
in
food
will
utilize
less
than
0.2
percent
of
the
cRfD
for
the
U.
S.
population.
EPA
generally
has
no
concern
7
for
exposures
below
100
percent
of
the
RfD
because
the
RfD
represents
the
level
at
or
below
which
daily
aggregate
dietary
exposure
over
a
lifetime
will
not
pose
appreciable
risks
to
human
health.
Despite
the
potential
for
exposure
to
Smetolachlor
in
drinking
water
and
from
non­
dietary,
non­
occupational
exposures,
the
assessment
presented
above
demonstrates
that
the
high
levels
of
safety
exist
for
current
and
proposed
uses
of
S­
metolachlor;
it
is
not
expected
that
aggregate
exposure
from
all
sources
will
exceed
100%
of
the
RfD.
Therefore,
one
can
conclude
there
is
a
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
S­
metola.
chlor.]

2.
Infants
and
children
FFDCA
section
408
provides
that
EPA
may
apply
an
additional
safety
factor
for
infants
and
children
in
the
case
of
threshold
effects
to
account
for
pre­
and
post­
natal
toxicity
and
the
completeness
of
the
database.
Based
on
the
current
toxicological
data
requirements,
the
database
relative
to
pre­
and
post­
natal
effects
for
children
is
complete.
A
full
consideration
of
the
available
reproductive
toxicity
data
supporting
S­
metolachlor
demonstrates
no
increased
sensitivity
to
infants
and
children.
Therefore,
it
is
concluded
that
an
additional
uncertainty
factor
is
not
warranted
to
protect
the
health
of
infants
and
children
and
that
the
cRfD
at
0.1
mg/
kg/
day
is
appropriate
for
assessing
aggregate
risk
to
infants
and
children
from
use
of
S­
metolachlor
.
EPA
concurred
with
this
in
the
TRED
released
for
public
comment
in
October
2002.

Based
on
the
aggregate
assessment
described
above,
the
percent
of
the
cRfD
that
will
be
utilized
by
aggregate
exposure
to
residues
of
S­
metolachlor
is
less
than
0.7
percent
for
all
children
subpopulations.
EPA
generally
has
no
concern
for
exposures
below
100%
of
the
RfD
because
the
RfD
represents
the
level
at
or
below
which
daily
aggregate
dietary
exposure
over
a
lifetime
will
not
pose
appreciable
risks
to
human
health.
Despite
the
potential
for
exposure
to
S­
metolachlor
in
drinking
water
and
from
non­
dietary,
non­
occupational
exposure,
the
assessment
described
above
demonstrates
that
it
is
not
expected
that
aggregate
exposure
from
all
sources
provides
for
a
large
margin
of
safety
and
will
exceed
100%
of
the
RfD.
Therefore,
based
on
the
completeness
and
reliability
of
the
toxicity
data
and
the
exposure
assessment,
it
is
concluded
there
is
a
reasonable
certainty
that
no
harm
will
result
to
infants
and
children
from
aggregate
exposure
to
S­
metolachlor
residues.]

F.
International
Tolerances
[
There
are
no
Codex
Alimentarius
Commission
(
CODEX)
maximum
residue
levels
(
MRL s)
established
for
residues
of
S­
metolachlor
in
or
on
raw
agricultural
commodities.]