Document ID: EPA-HQ-OPP-2006-0523-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-07-18T04:00Z

1
EPA
Registration
Division
contact:
Dani
Daniel,
703­
305­
5409
Barbara
Madden,
703­
305­
6463
Syngenta
Crop
Protection
Inc.
and
Interregional
Research
Project
#
4
(
IR­
4)

PP#
6E7060,
0F6142
and
9F5051
EPA
has
received
pesticide
petitions
(
PP#
9F5051
and
0F6142)
from
Syngenta
Crop
Protection
Inc.,
P.
O.
Box
18300,
Greensboro,
NC
27419­
8300
and
pesticide
petition
(
PP#
6E7060)
from
Interregional
Research
Project
#
4
(
IR­
4),
681
US
Highway
#
1
South,
North
Brunswick,
NJ
08902­
3390
,
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
180.565
by
establishing
a
tolerance
for
residues
of
thiamethoxam
[
3­[(
2­
chloro­
5­
thiazolyl)
methyl]
tetrahydro­
5­
methyl­
Nnitro
4H­
1,3,5­
oxadiazin­
4­
imine]
(
CAS
Reg.
No.
153719­
23­
4)
and
its
metabolite
[
N­(
2­
chlorothiazol
5­
ylmethyl)­
N'­
methyl
­
N'­
nitro­
guanidine]
in
or
on
the
raw
agricultural
commodities:
grapes
at
0.15
parts
per
million
(
ppm)
(
0F6142);
grape
juice
at
0.20
ppm
(
0F6142)
and
raisins
at
0.30
ppm
(
0F6142);
vegetable,
leafy,
except
brassica,
group
4
at
2.0
ppm
(
9F5051);
brassica,
leafy
greens,
subgroup
5B
at
2.0
ppm
(
9F5051);
brassica,
head
and
stem,
subgroup
5A
at
1.0
ppm
(
9F5051);
caneberry
subgroup
13A
at
0.30
ppm
(
6E7060);
hops
at
0.1
ppm
(
6E7060);
Globe
artichoke
at
0.4
ppm
(
6E7060)
and
tolerance
increases
for
barley,
grain
at
0.3
ppm
(
6E7060);
barley,
hay
at
0.4
ppm
(
6E7060);
and
barley,
straw
at
0.4
ppm
(
6E7060).
EPA
has
determined
that
the
petition
contains
data
or
information
regarding
the
elements
set
forth
in
section
408(
d)(
2)
of
the
FFDCA;
however,
EPA
has
not
fully
evaluated
the
sufficiency
of
the
submitted
data
at
this
time
or
whether
the
data
supports
granting
of
the
petition.
Additional
data
may
be
needed
before
EPA
rules
on
the
petition.

A.
Residue
Chemistry
1.
Plant
metabolism.
[
The
primary
metabolic
pathways
of
thiamethoxam
in
plants
(
corn,
cucumbers,
lettuce,
rice,
and
pears)
were
similar
to
those
described
for
animals,
with
certain
extensions
of
the
pathway
in
plants.
Parent
compound
and
CGA­
322704
were
the
major
residues
in
all
crops.
The
metabolism
of
thiamethoxam
in
plants
and
animals
is
understood
for
the
purposes
of
the
proposed
tolerances.
Parent
thiamethoxam
and
the
metabolite,
CGA­
322704,
are
the
residues
of
concern
for
tolerance
setting
purposes.]

2.
Analytical
method.
[
Syngenta
Crop
Protection
Inc.
has
submitted
practical
analytical
methodology
for
detecting
and
measuring
levels
of
thiamethoxam
in
or
on
raw
agricultural
commodities.
The
method
is
based
on
crop
specific
cleanup
procedures
and
determination
by
liquid
chromatography
with
either
UV
or
MS
detection.
The
limit
of
detection
(
LOD)
for
each
analyte
of
this
method
is
1.25
ng
injected
for
samples
analyzed
by
UV
and
0.25
ng
injected
for
2
samples
analyzed
by
MS,
and
the
limit
of
quantitation
(
LOQ)
is
0.005
ppm
for
milk
and
juices
and
0.01
ppm
for
all
other
substrates.
]

3.
Magnitude
of
residues.
[
IR­
4
has
submitted
complete
residue
data
for
thiamethoxam
on
hops,
caneberries,
globe
artichokes
and
barley.

Syngenta
has
submitted
complete
residue
data
for
the
proposed
tolerances
on
leafy
vegetables,
head
and
stem
brassica
vegetables,
leafy
brassica
vegetables
and
grape
commodities.]

B.
Toxicological
Profile
1.
Acute
toxicity.
[
The
acute
oral
LD50
for
thiamethoxam
in
the
rat
is
1563
mg/
kg
body
weight.
The
acute
dermal
LD50
of
thiamethoxam
is
>
2000
mg/
kg
body
weight.
Thiamethoxam
is
non­
toxic
at
atmospheric
concentrations
of
3.72
mg/
l.
Thiamethoxam
is
minimally
irritating
to
the
eye,
non­
irritating
to
skin
and
is
not
a
dermal
sensitizer.

In
an
acute
neurotoxicity
screening
study
in
rats
(
OPPTS
870.6200a),
the
NOAEL
was
100
mg/
kg/
day
with
a
NOAEL
of
500
mg/
kg/
day
based
on
drooped
palpebral
closure,
decrease
in
rectal
temperature
and
locomotor
activity
and
increase
in
forelimb
grip
strength
(
males
only).
At
higher
dose
levels,
mortality,
abnormal
body
tone,
ptosis,
impaired
respiration,
tremors,
longer
latency
to
first
step
in
the
open
field,
crouched
over
posture,
gait
impairment,
hypo­
arousal,
decreased
number
of
rears,
uncoordinated
landing
during
the
righting
reflex
test,
slight
lacrimation
(
females
only)
and
higher
mean
average
input
stimulus
value
in
the
auditory
startle
response
test
(
males
only).]

2.
Genotoxicty.
[
In
gene
mutation
studies
with
S.
typhimurium
and
E.
coli
(
OPPTS
870.5100
and
870.5265),
there
was
no
evidence
of
gene
mutation
when
tested
up
to
5000
ug/
plate
and
there
was
no
evidence
of
cytotoxicity.

In
a
gene
mutation
study
with
chinese
hamster
V79
cells
at
the
HGPRT
locus
(
OPPTS
870.5300)
there
was
no
evidence
of
of
gene
mutation
when
tested
up
to
the
solubility
limit.

In
a
CHO
cell
cytogenetics
study
(
OPPTS
870.5375)
there
was
no
evidence
of
chromosomal
aberrations
when
tested
up
to
cytotoxic
or
solubility
limit
concentrations.

An
in
vivo
mouse
bone
marrow
micronucleus
study
(
OPPTS
870.5395)
was
negative
for
clastogenic
effects
when
tested
up
to
levels
that
induced
significant
toxicity
in
whole
animals;
There
was
no
evidence
of
target
cell
cytotoxicity.
3
A
unscheduled
DNA
synthesis
(
UDS)
assay
(
OPPTS
870.5550)
was
negative
when
tested
up
to
precipitating
concentrations.]

3.
Reproductive
and
developmental
toxicity.
[
A
prenatal
developmental
study
in
the
rat
(
OPPTS
870.3700a)
resulted
in
Maternal
and
Developmental
NOAELs
of
30
mg/
kg/
day
and
200
mg/
kg/
day,
respectively.
The
maternal
LOAEL
is
200
mg/
kg/
day
based
on
decreased
body
weight,
body
weight
gain
and
food
consumption.
The
developmental
LOAEL
was
750
mg/
kg/
day
based
on
decreased
fetal
body
weight
and
an
increased
incidence
of
skeletal
anomalies.
There
was
no
evidence
of
any
teratogenic
effects.

A
prenatal
developmental
study
in
the
rabbit
(
OPPTS
870.3700b)
resulted
in
maternal
and
developmental
NOAELs
of
50
mg/
kg/
day.
The
maternal
and
developmental
LOAEL
is
150
mg/
kg/
day.
The
maternal
LOAEL
is
based
on
maternal
deaths,
hemorrhagic
discharge,
decreased
body
weight
and
food
intake
during
the
dosing
period.
The
developmental
LOAEL
is
based
on
decreased
fetal
body
weights,
increased
incidence
of
post­
implantation
loss
and
a
slight
increase
in
the
incidence
of
a
few
skeletal
anomolies/
variations.
There
was
no
evidence
of
any
teratogenic
effects
related
to
treatment.

A
2­
generation
reproduction
study
in
rats
was
conducted
according
to
the
most
current
EPA
guidelines
(
OPPTS
870.3800)
at
dose
levels
of
0,
20,
50,
1000
and
2500
ppm.
An
older
2­
generation
reproduction
study
in
hte
same
strain
of
rats
was
conducted
at
dose
levels
of
0,
10,
30,
1000
and
2500
ppm.
There
were
no
effects
on
reproductive
performance
in
either
study.
Considering
both
studies
together,
the
NOAEL
for
parental/
systemic
effects
was
50
ppm
(
3.0
mg/
kg/
day)
in
males
and
2500
ppm
(
208.8
mg/
kg/
day)
in
females,
based
upon
kidney
histopathology
in
males
only
at
1000
ppm
(
74.8
mg/
kg/
day).
The
overall
NOAEL
for
reproductive
effects
was
2500
ppm,
equivalent
to
155.6
mg/
kg/
day
in
males
and
208.8
mg/
kg/
day
in
females.
For
offspring
toxicity,
the
NOAEL
was
1000
pmm
(
74.8
mg/
kg/
day
in
males
and
110.1
mg/
kg/
day
in
females),
based
on
lower
body
weight
gain
during
late
lactation
at
2500
ppm.]

4.
Subchronic
toxicity.
[
A
90
day
oral
toxicity
study
in
rats
(
OPPTS
870.3100)
resulted
in
NOAEL
values
of
1.74
(
males),
92.5
(
females)
mg/
kg/
day.
The
LOAEL
values
were
17.64
(
male),
182.1
(
female)
mg/
kg/
day
based
on
increased
incidence
of
hyaline
change
of
renal
tubules
epithelium
(
males),
fatty
change
in
adrenal
gland
of
females
and
liver
changes
in
females,
all
at
the
LOAEL.

A
90
day
oral
toxicity
study
in
mice
(
OPPTS
870.3100)
resulted
in
NOAEL
values
of
1.41
(
males),
19.2
(
females)
mg/
kg/
day.
The
LOAEL
values
were
14.3
(
male),
231
(
female)
mg/
kg/
day
based
on
increased
incidence
of
hepatocellular
hypertrophy.
At
higher
dose
levels:
decrease
in
body
weight
and
body
weight
gain,
necrosis
of
individual
hepatocytes,
pigmentation
of
Kupffer
cells,
and
lymphocytic
infiltration
of
the
liver
in
both
sexes;
slight
hematologic
effects
and
decreased
absolute
and
relative
kidney
weights
in
males;
and
ovarian
atrophy,
decreased
ovary
and
spleen
weights
and
increased
liver
weights
in
females.
4
In
a
90
day
oral
toxicity
study
in
dogs
(
OPPTS
870.3150),
the
NOAEL
is
8.23
(
males),
9.27
(
females)
mg/
kg/
day.
The
LOAEL
is
32.0
(
male),
33.9
(
female)
mg/
kg/
day
based
on
slightly
prolongeed
prothrombin
times
and
decreased
plasma
albumin
and
A/
G
ratio
(
both
sexes);
decreased
calcium
levels
and
ovary
weights
and
delayed
maturation
in
the
ovaries
(
female);
decreased
cholesterol
and
phospholipid
levels,
testis
weights,
spermatogenesis,
and
increased
spermatic
giant
cells
in
testes
(
male).

In
a
28
day
dermal
study
in
rats
(
OPPTS
870.3200)
the
NOAEL
was
250
(
male),
60
(
female)
mg/
kg/
day.
The
LOAEL
was
1000
(
male),
250
(
female)
mg/
kg/
day
based
on
increased
plasma
glucose,
triglyceride
levels,
and
alkaline
phosphatase
activity
and
inflammatory
cell
infiltration
in
the
liver
and
necrosis
of
single
hepatocytes
in
females
and
hyaline
change
in
renal
tubules
and
a
very
slight
reduction
in
body
weight
in
males.
At
higher
dose
levels
in
females,
chronic
tubular
lesions
in
the
kidneys
and
inflammatory
cell
infiltration
in
the
adrenal
cortex
were
observed.

In
a
subchronic
neurotoxicity
screening
study
in
rats
(
OPPTS
870.6200b)
the
NOAEL
was
95.4
(
male),
216.4
(
female)
mg/
kg/
day,
both
at
highest
dose
tested.
There
were
no
treatment
related
systemic
effects,
neurotoxicity
signs,
or
histopathology
findings
in
the
central
or
peripheral
nervous
system.
A
LOAEL
for
neurotoxicological
and
systemic
effects
was
not
established.

In
a
developmental
neurotoxicity
(
DNT)
study,
a
dietary
level
of
4000
ppm
resulted
in
clear
maternal
toxicity,
with
lower
bodyweights
and
food
consumption,
and
lower
pup
bodyweights
at
birth.
There
was
no
effect
on
the
development
of
F1
animals
as
assessed
by
the
functional
observation
battery,
locomotor
activity,
auditory
startle
response,
or
performance
in
learning
and
memory
tests.
No
neuropathological
effects
of
treatment
were
observed.
The
NOAEL
for
developmental
toxicity
was
4000
ppm,
the
highest
dose
tested
(
equivalent
to
298.7
­
593.5
mg/
kg/
day
for
maternal
females
during
gestation
and
post­
partum,
respectively).]

5.
Chronic
toxicity.
[
In
a
chronic
toxicity
study
in
dogs
(
OPPTS
870.4100)
the
NOAEL
was
4.05
(
male),
4.49
(
female)
mg/
kg/
day.
The
LOAEL
was
21.0
(
male),
24.6
(
female)
mg/
kg/
day
based
on
increase
of
creatinine
in
both
sexes,
transient
decrease
in
food
consumption
in
females,
and
occasional
increase
in
urea
levels,
decrease
in
ALT,
and
a
slight
increase
in
atrophy
of
seminiferous
tubules
in
males.

In
a
mouse
carcinogenicity
study
(
OPPTS
870.4200)
the
NOAEL
was
2.63
(
male),
3.68
(
female)
mg/
kg/
day.
The
LOAEL
was
63.8
(
male),
87.6
(
female)
mg/
kg/
day
based
on
hepatocyte
hypertrophy,
single
cell
necrosis,
inflammatory
cell
infiltration,
pigment
deposition,
foci
of
cellular
alteration,
hyperplasia
of
Kupffer
cells
and
increased
mitotic
activity,
also
an
increase
in
the
incidence
of
hepatocellular
adenoma
(
both
sexes).
At
higher
doses,
there
was
an
increase
in
the
incidence
of
hepatocelluar
adenocarcinoma
(
both
sexes)
and
the
number
of
animals
with
multiple
tumors,
evidence
of
carcinogenicity
in
the
liver.
Investigative
work
demonstrated
that
the
formation
of
liver
tumors
is
specific
to
the
mouse
and
arises
due
to
a
non­
genotoxic
mode
of
action.
The
combination
of
factors
leading
to
the
development
of
liver
tumors
in
mice
do
not
5
occur
in
humans.
Therefore,
humans
are
not
at
risk
of
developing
liver
tumors
due
to
exposure
to
thiamethoxam.

In
a
combined
chronic
caricinogenicity
study
in
rats
(
OPPTS
870.4300)
the
NOAEL
was
21.0
(
male),
50.3
(
female)
mg/
kg/
day.
The
LOAEL
was
63.0
(
male),
255
(
female)
mg/
kg/
day
based
on
increased
incidence
of
lymphocytic
infiltration
of
the
renal
pelvis
and
chronic
nephropathy
in
males
and
decreased
body
weight
gain,
slight
increase
in
the
severity
of
hemosiderosis
of
the
spleen,
foci
of
cellular
alteration
in
liver
and
chronic
tubular
lesions
in
kidney
in
females.
No
evidence
of
carcinogenicity.
Investigative
work
demonstrated
that
effects
in
the
kidneys
of
male
rats,
in
subchronic
as
well
as
chronic
studies,
were
secondary
to
treatment
related
increase
in
alpha­
2u­
globulin
associated
kidney
injury
is
unique
to
the
male
rat.
Therefore,
these
kidney
findings
in
the
male
rat
are
of
no
relevance
to
human
risk
assessment.]

6.
Animal
metabolism.
[
The
metabolism
of
thiamethoxam
in
rats
and
livestock
animals
is
adequately
understood.
The
residues
of
concern
have
been
determined
to
be
parent
thiamethoxam
and
its
metabolite
(
N­(
2­
chloro­
thiazol­
5­
ylmethyl)­
N'methyl­
N"­
nitro­
guanidine.]

7.
Metabolite
toxicology.
[
For
most
risk
assessment
purposes,
residues
of
the
metabolite
corrected
for
molecular
weight
are
considered
to
be
toxicologically
equivalent
to
parent
thiamethoxam.]

8.
Endocrine
disruption.
[
There
is
no
indication
from
the
mammalian
toxicology
database
for
any
endocrine
disrupting
effect
of
thaimethoxam]

C.
Aggregate
Exposure
1.
Dietary
exposure.
Tier
I
acute,
chronic
and
short­
term
aggregate
risk
assessments
were
made
for
thiamethoxam
using
the
Dietary
Exposure
Evaluation
Model
(
DEEM­
FCIDTM
,
version
2.03)
from
Exponent.
In
addition
to
established
tolerances
(
40CFR180.565)
for
the
combined
residues
of
thiamethoxam
,
3­[(
2­
chloro­
5­
thiazolyl)
methyl]
tetrahydro­
5­
methyl­
N­
nitro­
4H­
1,3,5­
oxadiazin­
4­
imine]
and
it's
metabolite
[
N­(
2­
chloro­
thiazol­
5­
ylmethyl)­
N'­
methyl­
N'­
nitroguanidine
in
or
on
a
variety
of
raw
agricultural
commodities
including
meat
and
milk,
these
exposure
assessments
included
all
pending
and
proposed
crop
uses
and
a
proposed
use
in
turf
(
including
residential
turf).
Pending
tolerances
include
grapes
(
0.05
ppm),
grape
raisins
(
0.30
ppm),
grape
juice
(
0.20
ppm),
Brassica
head
and
stem
vegetables
(
1.0
ppm),
leafy
Brassica
vegetables
(
2.0
ppm)
and
leafy
vegetables
(
2.0
ppm).
Proposed
crop
tolerances
include
hops
(
0.1
ppm),
caneberries
(
0.3
ppm),
globe
artichoke
(
0.4
ppm),
barley
grain
(
0.3
ppm),
barley
straw
(
0.4
ppm)
and
barley
hay
(
0.4
ppm).
Percent
crop
treated
values
were
conservatively
estimated
to
be
6
100%
for
all
established,
pending
and
proposed
uses.
Drinking
water
estimates
were
incorporated
directly
into
the
dietary
exposure
assessments
using
the
highest
estimated
drinking
water
concentrations
(
EDWCs)
for
surface
and
ground
water.
All
consumption
data
for
these
assessments
was
taken
from
the
USDA's
Continuing
Survey
of
Food
Intake
by
individuals
(
CSFII)
with
the
1994­
96
consumption
database
and
the
Supplemental
CSFII
children's
survey
(
1998)
consumption
database.

In
the
tier
II
chronic
assessment,
the
residue
of
concern
was
the
sum
of
CGA­
293343
and
CGA­
322704.
Addition
of
the
proposed
crops
mentioned
above
to
the
animal
diets
did
not
increase
the
previously
calculated
dietary
burdens
for
any
livestock
commodities.
Therefore,
the
residue
values
for
secondary
animal
commodities
were
taken
from
the
EPA
assessment
of
August
28,
2000
which
uses
average
field
trial
residue
data
with
½
LOQ
substitutions
for
all
non­
detectable
residues.
For
the
remaining
registered
and
the
proposed
commodities
listed
above,
the
following
residue
data
was
used
in
the
DEEMTM:
cucurbit,
leafy
and
Brassica
vegetables
and
tomatoes
­
average
field
trial
residues
from
soil­
only
(
Platinum)
application
residue
studies;
stone
fruits,
mint,
succulent
beans,
sunflower
seed,
and
coffee
­
average
field
trial
residue
data
with
½
LOQ
substitutions
for
non­
detectable
residues;
all
other
commodities
­
the
proposed
tolerances
listed
in
the
acute
section
above.

i.
Food.
Acute
Exposure
The
thiamethoxam
acute
dietary
(
food
only)
risk
assessment
was
performed
on
all
population
subgroups
using
an
acute
reference
dose
(
aRfD)
of
1.0
mg/
kg­
bw/
day
based
upon
an
acute
neurotoxicity
study
in
rats
with
a
no
observable
effect
level
(
NOAEL)
of
100
mg/
kg/
day
and
an
uncertainly
factor
of
100X.
No
additional
FQPA
safety
factor
was
applied.
For
the
purpose
of
aggregate
risk
assessment,
the
exposure
value
was
expressed
in
terms
of
margin
of
exposure
(
MOE).
The
MOE
was
calculated
by
dividing
the
no
observable
adverse
effect
level
(
NOAEL)
by
the
exposure
for
each
population
subgroup.
In
addition,
exposure
was
expressed
as
a
percent
of
the
acute
reference
dose
(%
aRfD).
At
the
95th
percentile
of
exposure,
acute
(
food
only)
exposure
to
the
U.
S.
population
resulted
in
an
MOE
of
13,205
(
0.76%
of
the
aRfD
of
1.0
mg/
kg­
bw/
day.
The
most
exposed
sub­
population
was
children
(
1­
2
years
old)
with
an
MOE
of
5,615
(
1.78%
of
the
aRfD.
Since
the
benchmark
MOE
for
this
assessment
was
100
and
since
EPA
generally
has
no
concern
for
exposures
below
100%
of
the
acute
RfD,
Syngenta
believes
that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
acute
dietary
(
food)
exposure
to
residues
arising
from
the
current
and
proposed
uses
for
thiamethoxam.

Chronic
Exposure
The
thiamethoxam
chronic
dietary
(
food
only)
risk
assessment
was
performed
for
all
population
subgroups
using
a
chronic
reference
dose
(
cRfD)
of
0.041
mg/
kg­
bw/
day
based
upon
a
twelvemonth
study
in
dogs
with
a
no
observable
adverse
effect
level
(
NOAEL)
of
4.1
mg/
kg/
day
and
an
uncertainty
factor
of
100X
(
factor
includes
intra­
and
inter­
species
variations
.
No
additional
FQPA
was
applied.
For
the
purpose
of
aggregate
risk
assessment,
the
exposure
values
were
7
expressed
in
terms
of
margin
of
exposure
(
MOE),
which
was
calculated
by
dividing
the
NOAEL
by
the
exposure
for
each
population
subgroup.
In
addition,
exposure
was
expressed
as
a
percent
of
the
chronic
reference
dose
(%
RfD).
Chronic
(
food
only)
exposure
to
the
U.
S.
population
resulted
in
an
MOE
of
1,633
(
6.1%
of
the
RfD
of
0.041
mg/
kg­
bw/
day).
The
most
exposed
subpopulation
was
children
(
1­
2
years
old)
with
an
MOE
of
582
(
17.2%
of
the
RfD).
Since
the
benchmark
MOE
for
this
assessment
was
100
and
since
EPA
generally
has
no
concern
for
exposures
below
100%
of
the
RfD,
Syngenta
believes
that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
chronic
dietary
(
food)
exposure
to
residues
arising
from
the
current
and
proposed
uses
for
thiamethoxam.

Cancer
A
quantitative
risk
assessment
for
cancer
is
not
required.

ii.
Drinking
water.
The
EPA
uses
the
screening
model
FIRST
to
estimate
potential
surface
water
concentrations
and
the
screening
model
SCI­
GROW
to
estimate
potential
ground
water
concentrations.
None
of
these
models
include
consideration
of
the
impact
of
processing
(
mixing,
dilution,
or
treatment)
would
have
on
the
removal
of
pesticides
from
the
water
source
prior
to
distribution
as
drinking
water.
The
primary
use
of
these
models
is
to
provide
a
conservative
approximation
of
the
Estimated
Drinking
Water
Concentrations
(
EDWCs)
of
specific
pesticides
in
drinking
water.
These
models
were
used
by
Syngenta
to
provide
EDWCs
of
thiamethoxam
for
a
proposed
use
on
turf
grass
at
a
maximum
application
rate
of
0.266
lb
ai/
A
using
ground
application
equipment.
Note
that
the
surface
water
modeling
utilized
a
highly
conservative
percent
cropped
area
(
PCA)
of
100%
to
provide
a
theoretical
worst­
case
estimate
of
thiamethoxam
exposure
based
upon
the
unlikely
assumption
that
the
entire
watershed
is
both
covered
with
turf
and
treated
by
ground
application
on
the
same
day
at
the
maximum
label
rate.
Based
upon
these
assumptions,
Syngenta
calculated
the
highest
screening
level
EDWCs
of
25.687
ppb
for
acute
surface
water
and
4.12
ppb
for
chronic
ground
water.

Acute
Exposure
from
Drinking
Water
The
acute
EDWC
of
25.697
ppb
(
surface
water)
was
used
to
calculate
the
acute
drinking
water
exposure
values
for
the
U.
S.
Population
and
population
subgroups.
Acute
drinking
water
estimates
were
incorporated
directly
into
the
DEEM­
FCIDTM
software
along
with
current,
pending
and
proposed
uses
of
thiamethoxam.
Acute
exposure
(
food
and
water)
to
the
U.
S.
Population
resulted
in
an
MOE
of
12,008
(
0.83%
of
the
RfD).
The
most
exposed
subpopulation
was
children
(
1­
2
years
old)
with
an
MOE
of
5,328
(
1.88%
of
the
aRfD).
Since
the
benchmark
MOE
for
this
assessment
was
100
and
since
EPA
generally
has
no
concern
for
exposures
below
100%
of
the
RfD,
Syngenta
believes
that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
chronic
dietary
(
food)
exposure
to
residues
arising
from
the
current
and
proposed
uses
for
thiamethoxam.
8
Chronic
Exposure
form
Drinking
Water:
The
chronic
EDWC
of
4.12
ppb
(
groud
water)
was
used
to
calculate
the
chronic
drinking
water
exposure
values
for
the
U.
S.
Population
and
population
subgroups.
Chronic
drinking
water
estimates
were
incorporated
directly
into
DEEM­
FCIDTM
software
along
with
current,
pending
and
proposed
uses
of
thiamethoxam.
Chronic
exposure
(
food
and
water)
to
the
U.
S.
Population
resulted
in
an
MOE
of
1,578
(
6.3%
of
the
cRfD).
The
most
exposed
sub­
population
was
children
(
1­
2
years
old)
with
an
MOE
of
572
(
17.5%
of
the
cRfD).
Since
the
benchmark
MOE
for
this
assessment
was
100
and
since
EPA
generally
has
no
concern
for
exposures
below
100%
of
the
RfD,
Syngenta
believes
that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
chronic
dietary
(
food)
exposure
to
residues
arising
from
the
current
and
proposed
uses
for
thiamethoxam.

2.
Non­
dietary
exposure.
Residential
(
non­
occupational)
short­
term
risk
assessments
were
conducted
for
professional
uses
of
thiamethoxam
on
residential
turf
with
a
maximum
rate
of
0.266
lbs
ai/
A
(
one
application
per
year).
Based
upon
the
use
pattern,
there
is
no
residential
handler
exposure
and
only
short­
term
exposures
were
investigated
since
use
of
the
turf
product
would
not
be
expected
to
exceed
30
days.
The
following
endpoints
were
used
for
these
residential
risk
assessments:
NOAEL=
30
mg/
kg/
day
(
short
term
oral
from
a
rat
developmental
toxicity
study)
and
NOAEL=
60
mg/
kg/
day
(
short­
term
dermal
fro
a
28­
day
dermal
study
in
rats).
Post
application
dermal
exposure
risks
were
evaluated
for
adults
re­
entering
treated
yards.
The
resultant
short­
term
MOE
for
adults
is
832
which
is
above
the
benchmark
MOE
of
100
and
thus
does
not
exceed
EPA's
level
of
concern.
Post
application
dermal
exposure
risks
were
also
evaluated
for
children
(
1­
5
years
old)
re­
entering
treated
yards.
Additionally,
post
application
oral
exposure
risks
were
assessed
for
children
engaged
in
hand­
to­
mouth,
object­
to­
mouth
and
treated
soil
ingestion
activities.
The
resultant
combined
short­
term
MOE
for
children
is
529
which
is
above
the
benchmark
MOE
of
100
and
thus
does
not
exceed
EPA's
level
of
concern.

D.
Cumulative
Effects
Cummulative
Exposure
to
Substances
with
a
Common
Mechanism
of
Toxicity.
Section
408(
b)(
2)(
D)(
v)
of
FFDCA
requires
that,
when
considering
whether
to
establish,
modify,
or
revoke
a
tolerance,
the
Agency
consider
"
available
information"
concerning
the
the
cummulative
effects
of
a
particular
pesticide's
residues
and
"
other
substances
that
have
a
common
mechanism
of
toxicity".
Unlike
other
pesticides
for
which
EPA
has
followed
a
cummulative
risk
approach
based
upon
a
common
mechanism
of
toxicity,
EPA
has
not
made
a
common
mechanism
of
toxicity
finding
as
to
thiamethoxam
and
any
other
substances
and
thaimethoxam
does
not
appear
to
produce
a
toxic
metabolite
produced
by
other
substances.
For
the
purposes
of
htis
tolerance
action,
the
EPA
has
not
assumed
that
thiamethoxam
has
a
common
mechanism
of
toxicity
with
other
substances.
9
E.
Safety
Determination
1.
U.
S.
population.
The
acute
dietary
exposure
analysis
(
food
plus
water)
and
chronic
dietary
exposure
analysis
(
food
plus
water)
showed
that
exposure
to
the
U.
S.
Population
from
all
established,
pending
and
proposed
uses
is
well
above
the
benchmark
MOE
of
100
with
MOEs
of
12,008(
0.83%
of
aRfD)
and
1,578
(
6.3%
of
cRfD),
respectively.
A
short­
term
aggregate
exposure
analysis
(
food,
water
and
residential)
was
required
for
adults
because
there
is
a
postapplication
dermal
exposure
scenario
from
re­
entry
into
treated
turf.
The
corresponding
MOEs
were
aggregated
using
the
inverse
MOE
approach.
For
short­
term
exposures,
the
dietary
(
food
and
water)
exposure
(
MOE
11,547)
was
aggregated
with
residential
exposure
(
MOE
832)
resulting
in
a
short­
term
aggregate
MOE
of
776
for
the
U.
S.
Population
which
exceeds
the
benchmark
MOE
of
100.
An
intermediate
term
aggregate
exposure
analysis
(
food
plus
water
plus
residential)
was
not
required
for
adults
because
residential
turf
exposures
are
not
expected
to
occur
for
longer
than
a
short
time
frame.
Based
upon
the
completeness
and
reliability
of
the
toxicity
data
supporting
these
petitions,
Syngenta
believes
that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
residues
arising
from
all
currnet,
pending
and
proposed
thiamethoxam
uses,
including
anticipated
dietary
exposure
from
food,
water
and
all
other
types
of
non­
occupational
exposures.
]

2.
Infants
and
children.
The
acute
dietary
exposure
analysis
(
food
plus
water)
showed
that
exposure
from
all
established,
pending
and
proposed
uses
would
result
in
an
MOE
of
5,328
(
1.88%
of
the
aRfD)
for
the
most
sensitive
population
subgroup,
children
1­
2
years
old,
which
exceeds
the
benchmark
MOE
of
100.
The
chronic
aggregate
dietary
(
food
plus
water)
exposure
analysis
showed
that
exposure
form
all
established,
pending
and
proposed
thiamethoxam
uses
would
result
in
an
MOE
of
572
(
17.5%
of
hte
cRfD)
fo
rthe
most
sensitive
population
subgroup,
children
1­
2
years
old,
which
exceeds
the
benchmark
MOE
of
100.
A
short­
term
aggregate
exposure
analysis
(
food,
water
and
residential)
was
required
for
toddlers
because
there
are
residential
post­
application
dermal
and
oral
exposure
scenarios
from
re­
entry
into
treated
turf.
For
short­
term
exposures,
the
dietary
(
food
plus
water)
exposure
(
MOE
4,184)
was
aggregated
with
residential
exposure
(
MOE
529)
resulting
in
a
short­
term
aggregate
MOE
of
470
for
the
most
sensitive
population
subgroup,
children
1­
2
years
old,
which
exceeds
the
benchmark
MOE
of
100.
An
intermediate­
term
aggregate
exposure
analysis
was
not
required
for
children
because
residential
turf
exposures
are
not
expected
to
occur
for
longer
than
a
short­
term
time
frame.
Based
upon
the
completeness
and
reliability
of
the
toxicity
data
supporting
these
petitions,
Syngenta
believes
that
there
is
a
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
residues
arising
from
all
current,
pending
and
proposed
thiamethoxam
uses,
including
anticipated
dietary
exposure
from
food,
water
and
all
other
types
of
non­
occupational
exposures.

F.
International
Tolerances
10
[
There
are
no
Codex
MRLs
established
for
residues
of
thiamethoxam.]