Document ID: EPA-HQ-OPP-2005-0298-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-01-18T05:00Z

FILE
NAME:
company.
wpt
(
1/
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
prompts
in
green
font
should
also
be
removed.

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

EPA
Registration
Division
contact:
[
insert
name
and
telephone
number
with
area
code]

INSTRUCTIONS:
Please
utilize
this
outline
in
preparing
tolerance
petition
documents.
In
cases
where
the
outline
element
does
not
apply
please
insert
"
NA­
Remove"
and
maintain
the
outline.
The
comment
notes
that
appear
on
the
left
margin
represent
hidden
typesetting
codes
designed
to
expedite
the
processing
of
the
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Register
document.
Please
do
not
remove
or
alter
these
comment
notes
or
change
the
margins,
font,
or
format
in
your
document.
Simply
replace
the
instructions
that
appear
in
italics
and
brackets,
i.
e.,
"[
insert
company
name],"
with
the
information
specific
to
your
action.

TEMPLATE:

[
Bayer
CropScience]

[
Insert
petition
number]
EPA
has
received
a
pesticide
petition
([
XXXXX])
from
[
Bayer
CropScience],
[
2
T.
W.
Alexander
Drive,
Research
Triangle
Park,
NC
27709]
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
by
establishing
a
tolerance
for
residues
of
clothianidin
in
or
on
the
raw
agricultural
commodities
[
cotton,
undelinted
seed
and
cotton,
gin
byproducts]
at
[
0.01]
parts
per
million
(
ppm).
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
2
1.
Plant
metabolism.
In
plants,
the
metabolism
of
clothianidin
is
adequately
understood
for
the
purposes
of
establishing
these
proposed
tolerances.
Unchanged
parent
clothianidin
was
the
predominant
residue
in
all
crop
matrices
(
14.4%
to
64.5%
in
corn,
66.1%
to
96.6%
in
tomatoes,
4.3%
to
24.4%
in
sugar
beets
and
24.3%
to
63.3%
in
apples),
with
the
exception
of
sugar
beet
leaves.
In
sugar
beet
leaves,
the
main
components
were
the
methylguanidine
and
thiazolylmethylguanidine
metabolites,
accounting
for
28.6%
and
27.7%,
respectively.
All
metabolites
found
in
plants
were
also
found
in
the
animal
metabolism
studies.
In
animals,
parent
clothianidin
was
the
major
component
in
liver,
muscle
and
fat.
Based
on
the
available
metabolism
data,
parent
clothianidin,
thiazolyl­
guanidine
(
TZG),
thiazolyl­
urea
(
TZU)
,
and
(
ATMG­
Pyr)
aminothiazolyl
methylguanidine­
pyridine
are
proposed
to
be
considered
as
the
residues
of
concern
in
livestock
matrices.
2.
Analytical
method.
In
plants
and
plant
products,
the
residue
of
concern,
parent
clothianidin,
can
be
determined
using
High
Performance
Liquid
Chromotography
(
HPLC)
with
Electrospray
MS/
MS
detection.
In
an
extraction
efficiency
testing,
the
plant
residues
method
has
also
demonstrated
the
ability
to
extract
aged
clothianidin
residue.

Although
the
plant
residues
LC­
MS/
MS
method
is
highly
suitable
for
enforcement
method,
an
LC­
UV
method
has
also
been
developed
which
is
suitable
for
enforcement
(
monitoring)
purposes
in
all
relevant
matrices.
3.
Magnitude
of
residues
in
cotton
­
A
total
of
12
field
trials
was
conducted
to
evaluate
the
quantity
of
clothianidin
in
cotton
seed
and
cotton
gin
byproducts.
Cotton
seed
was
treated
with
PONCHO
600
FS
at
a
rate
of
8.96
fl.
oz.
of
formulated
product
per
100
lbs
seed
(
350
g
ai/
100kg
seed).
No
clothianidin
residues
were
found
in
any
cotton
seed
or
cotton
gin
byproduct
samples
at
an
LOQ
of
0.01
ppm.
In
a
cotton
processing
study
cotton
seed
was
treated
at
a
5X
rate
of
1750
g
ai/
100
kg
seed.
No
residues
at
or
above
the
LOQ
of
0.01
ppm
were
found
in
the
cotton
seed.
Therefore,
a
cotton
processing
study
was
not
conducted.

B.
Toxicological
Profile
1.
Acute
toxicity.
The
acute
oral
LD
50
was
>
5,000
milligrams/
kilograms/
body
weight
(
mg/
kg
bw)
for
both
male
and
female
rats.
The
acute
dermal
LD
50
was
greater
than
2,000
mg/
kg
bw
in
rats.
The
4­
hour
inhalation
LC
50
was
5.538
mg/
L
for
male
and
female
rats.
Clothianidin
was
not
irritating
to
rabbit
skin
and
only
slightly
irritating
to
the
eyes
and
did
not
cause
skin
sensitization
in
guinea
pigs.

2.
Genotoxicty.
Extensive
mutagenicity
studies
were
conducted
with
clothianidin.
Based
on
the
weight
of
evidence
clothianidin
was
considered
negative
for
genotoxicity.
3.
Reproductive
and
developmental
toxicity.
In
a
2­
generation
reproduction
study,
rats
were
administered
dietary
levels
of
0,
150,
500
and
2500
ppm.
The
No
Observed
Effect
Level
(
NOAEL)
for
reproductive
parameters
was
500
ppm
(
31.2/
36.8
mg.
kg/
day;
M/
F)
while
the
NOAEL
for
developmental
effects
was
150
ppm
(
9.8/
11.5
mg/
kg/
day;
M/
F).
The
parental
systemic
NOAEL
was
500
ppm
(
31.2/
36.8
mg/
kg/
day;
M/
F).
3
A
developmental
toxicity
study
was
conducted
in
rats
with
clothianidin
using
dose
levels
of
0,
10,
50
and
125
mg/
kg
bw
by
gavage.
The
NOAEL
for
maternal
toxicity
was
established
at
10
mg/
kg
bw
and
for
developmental
effects
it
was
>
125
mg/
kg
bw.
Additionally,
a
developmental
toxicity
study
was
conducted
with
rabbits
treated
orally
by
gavage
at
0,
10,
25,
75
and
100
mg/
kg
bw.
The
NOAEL
for
maternal
toxicity
was
25
mg/
kg
bw
and
for
developmental
toxicity
it
was75
mg/
kg
bw.

Developmental
toxicity
studies
showed
no
primary
developmental
toxicity
and
no
teratogenic
potential
was
evident.

4.
Subchronic
toxicity.
Ninety­
day
feeding
studies
were
conducted
in
rats
and
dogs.
The
rat
study
was
conducted
at
dietary
levels
of
0,
150,
500
and
3,000
ppm
and
the
dog
study
was
conducted
at
0,
325,
650
and
1,500
ppm.
The
NOAELs
were
established
at
500
ppm
(
27.9/
34.0
mg/
kg/
day;
M/
F)
for
rat
and
650
ppm
(
19.3
mg/
kg/
day)
for
the
female
dog
and
1500
ppm
(
42.1
mg/
kg/
day)
for
the
female
dog.

5.
Chronic
toxicity.
A
2­
year
combined
rat
chronic
/
oncogenicity
conducted
at
dietary
levels
of
0,
150,
500,
1,500
and
3,000
ppm
demonstrated
a
NOAEL
of
500
ppm
(
27.9/
34.0
mg/
kg/
day)
based
on
reduced
weight
gains
and
non­
neoplastic
histomorphological
changes.
A
78­
week
mouse
oncogenicity
study
conducted
at
dose
levels
of
0,
100,
350,
1,250
and
2,000,
and
1,800
ppm
for
males
and
females,
respectively,
revealed
a
NOAEL
of
350
ppm
(
47.2/
65.1
mg/
kg/
day;
M/
F)
based
on
reduced
body
weight
gains
and
increased
incidence
of
hypercellular
hypertrophy.
No
evidence
of
oncogenicity
was
seen
in
the
rat
or
the
mice.
A
52­
week
chronic
toxicity
study
in
dogs
conducted
at
dietary
levels
of
0,
325,
650,
1,500
and
2,000
ppm
revealed
a
NOAEL
of
2000
ppm
(
46.4
mg/
kg/
day)
for
the
male
dog
and
1500
ppm
(
40.1
mg/
kg/
day)
for
the
female
dog.

6.
Animal
metabolism.
The
nature
of
the
clothianidin
residue
in
livestock
is
adequately
understood.
In
animals,
parent
clothianidin
was
the
major
component
in
liver,
muscle
and
fat.
Based
on
the
available
metabolism
data,
parent
clothianidin,
TZG,
TZU,
and
ATMG­
Pyr
are
proposed
to
be
considered
as
the
residues
of
concern
in
livestock
matrices.

7.
Metabolite
toxicology.
Eight
in
vivo
metabolites
of
clothianidin
identified
in
the
rat
were
investigated
for
acute
oral
endpoint
mutagenic
activity.
None
of
the
metabolites
were
mutagenic
either
with
or
without
activation
and
the
LD
50
values
range
from
<
500
to
>
2,000
mg/
kg,
showing
low
to
moderate
toxicity.

8.
Endocrine
disruption.
All
guideline
studies
conducted
to
characterize
toxicological
profile
showed
no
endocrine
related
toxicity
or
tumorgenicity.
No
effects
on
triiodothyronine
(
T3),
throxine
(
T4)
or
thyroid
stimulating
hormone
(
TSH)
were
observed
in
the
subchronic
rat
study.
In
a
2­
generation
reproduction
study
in
rat;
and
rat
and
rabbit
teratology
studies,
clothianidin
did
not
show
reproductive
or
teratogenic
effects.
The
extensive
database
shows
that
clothianidin
has
no
endocrine
properties.
4
C.
Aggregate
Exposure
1.
Dietary
Exposure.
There
are
no
residential
uses
for
clothianidin
therefore
aggregate
exposure
consisits
of
dietary
(
food
and
drking
water)
exposures.
The
acute
population
adjusted
dose
(
aPAD)
of
0.025
mg/
kg
bw/
day
based
on
a
acute
NOAEL
of
25
with
an
uncertainty
factor
of
1000
was
used
to
assess
acute
dietary
expsoure.
The
chronic
population
adjusted
dose
(
cPAD)
of
0.0098
mg/
kg
bw/
day
based
on
a
chric
NOAEL
of
9.8
with
an
unceratinty
factor
of
1000
was
used
to
assess
chronic
exposure.

i.
Food.
In
the
Clothianidin
Pesticide
Tolerance
Action
for
Corn
and
Canola
of
May
30,
2003
EPA
conducted
Tier
1
acute
and
chronic
dietary
assessments
for
clothianidin.
These
assessments
included
residues
of
clothianidin
that
arise
from
the
uses
of
thiamethoxam
which
has
clothianidin
as
a
common
metabolite.
In
December
2003,
Bayer
CropScience
submitted
a
tolerance
petition
for
registration
of
clothianidin
as
a
seed
treatment
on
sorghum
with
a
proposed
tolerance
of
0.01
ppm.
A
revised
dietary
assessment
was
conducted
which
added
the
proposed
sorghum
tolerance
of
0.01
ppm
as
well
as
the
cotton
tolerance
of
0.01
ppm
proposed
in
this
petition.
No
significant
contribution
was
seen
from
these
uses.
The
US
Population
utilized
8.4%
(
0.00211mg/
kg
bw/
day,
95th
percentile)
of
the
aPAD
and
6.5%
(
0.00064
mg/
kg
bw/
day)
of
the
cPAD.
The
most
highly
exposed
sub­
population
is
Children
1­
2
at
19.1%(
0.00477
mg/
kg
bw/
day,
95th
percentile)
of
the
aPAD
and
19.1%
(
0.001875
mg/
kg
bw/
day)
of
the
cPAD.

ii.
Drinking
Water.
US
EPA's
Standard
Operating
Procedure
(
SOP)
for
Drinking
Water
Exposure
and
Risk
Assessments
was
used
to
perform
the
drinking
water
assessment.
This
SOP
uses
a
variety
of
tools
to
conduct
drinking
water
assessment.
These
tools
include
water
models
such
as
SCI­
GROW,
FIRST,
PRZMS/
EXAMS,
and
monitoring
data.
If
monitoring
data
are
not
available
then
the
models
are
used
to
predict
potential
residues
in
surface
and
ground
water
and
the
highest
is
assumed
to
be
the
drinking
water
residue.
In
the
case
of
clothianidin
monitoring
data
do
not
exist
therefore
SCI­
GROW
and
FIRST
were
used
to
estimate
a
water
residue.
The
calculated
drinking
water
levels
of
comparison
(
DWLOC)
for
acute
chronic
exposure
for
all
adults
and
children
exceed
the
estimated
drinking
water
concentrations
(
EDWC)
from
the
models.
The
chronic
DWLOC
for
adults
is
321ppb
and
the
acute
DWLOC
is
801ppb.
The
chronic
DWLOC
for
children
1­
2
is
79ppb
and
the
acute
DWLOC
is
202ppb.
The
EDWC
for
the
worst
case
chronic
scenario
is
2.14ppb
(
FIRST)
and
the
acute
EDWC
(
FIRST)
is
3.97ppb.
The
drinking
water
levels
of
comparison
are
based
on
conservative
dietary
(
food)
exposures
and
are
expected
to
be
much
higher
in
real
world
situations.

2.
Non­
dietary
Exposure.
Clothianidin
is
currently
registered
for
use
on
turfgrasses.
Exposures
and
risk
resulting
from
the
clothianidin
residues
on
turfgrasses
were
included
in
the
EPA
risk
assessment
for
thiamethoxam
published
in
the
Federal
Register,
January
5,
2005
and
the
clothianidin
risk
assessment
published
in
the
Federal
Register,
February
16,
2005..

D.
Cumulative
Effects
5
Clothianidin
is
a
metabolite
of
thiamethoxam.
Therefore,
residues
of
clothianidin
resulting
from
use
of
thiamethoxam
were
included
in
the
above
risk
assessment.
Currently,
EPA
has
not
determined
that
toxic
effects
produced
by
clothianidin
are
cumulative
with
those
of
any
other
compound.

E.
Safety
Determination
1.
US
Population.
Using
the
conservative
exposure
assumptions
described
above
and
based
on
the
completeness
of
the
toxicity
data,
it
can
be
concluded
that
aggregate
exposure
to
residues
of
clothianidin
present
a
reasonable
certainty
of
no
harm.
Exposure
from
residues
in
crops
utilize
8.4%
of
the
aPAD
and
6.5%
of
the
cPAD.
EPA
generally
has
no
concerns
for
exposures
below
100%
of
the
Population
Adjusted
Doses.
Drinking
water
levels
of
concern
are
well
above
the
estimated
drinking
water
concentrations
as
calculated
by
conservative
models.
Clothianidin
is
registered
for
use
on
turf.
The
aggregate
exposure
to
the
U.
S.
Population
and
population
subgroups
was
assessed
by
EPA
and
published
in
the
Federal
Register
February
16,
2005.
The
cotton
use
does
not
increase
the
aggregate
exposure.
The
conservative
Tier
1
assessments
demonstrate
a
reasonable
certainty
of
no
harm
will
result
from
uses
of
clothianidin
for
the
US
Population.
2.
Infants
and
children.
In
assessing
the
potential
for
additional
sensitivity
of
infants
and
children
to
residues
of
clothianidin,
the
data
from
developmental
toxicity
studies
in
both
the
rat
and
rabbit,
a
2­
generation
reproduction
study
in
rats
and
a
developmental
neurotoxicity
study
in
rats
have
been
considered.

The
developmental
toxicity
studies
evaluate
potential
adverse
effects
on
the
developing
animal
resulting
from
pesticide
exposure
of
the
mother
during
prenatal
development.
The
reproduction
study
evaluates
effects
from
exposure
to
the
pesticide
on
the
reproductive
capability
of
mating
animals
through
two
generations,
as
well
as
any
observed
systemic
toxicity.

The
developmental
neurotoxicity
studies
evaluate
the
neurobehavioral
and
neurotoxic
effects
on
the
developing
animal
resulting
from
the
exposure
of
the
mother.
FFDCA
Section
408
provides
that
EPA
may
apply
an
additional
uncertainty
factor
for
infants
and
children
based
on
the
threshold
effects
to
account
for
prenatal
and
postnatal
effects
and
the
completeness
of
the
toxicity
database.
Based
on
the
current
toxicological
data
requirements
the
toxicology
database
for
clothianidin
relative
to
prenatal
and
postnatal
development
is
complete,
including
the
developmental
neurotoxicity
study.
None
of
the
studies
indicated
the
offsprings
to
be
more
sensitive.
All
effects
were
secondary
to
severe
maternal
toxicity.
Therefore,
no
additional
safety
or
uncertainty
factor
is
justified.

F.
International
Tolerances
No
CODEX
Maximum
Residue
Levels
(
MRL's)
have
been
established
for
residues
of
clothianidin
on
any
crops
at
this
time.
6