Page
1
STUDY
TITLE
FQPA
Supplemental
Information
Document
for
Zeta­
Cypermethrin
DATA
REQUIREMENT
No
Guideline
Number
Requirement
AUTHOR
Nancy
J.
Hilton
STUDY
COMPLETION
DATE
August
8,
2006
SPONSOR
FMC
Corporation
Philadelphia,
PA
PERFORMING
LABORATORY
FMC
Corporation
PROJECT
ID
NUMBER
FMC
Zeta­
cypermethrin
2004CROP.
rev
FMC
Zeta­
cypermethrin
2004CROP.
rev
Page
2
STATEMENT
OF
NO
DATA
CONFIDENTIALITY
CLAIMS
No
claim
of
confidentiality
is
made
for
any
information
contained
in
this
report
on
the
basis
of
its
falling
within
the
scope
of
FIFRA
Section
10
(
d)
(
1)
(
A),
(
B),
or
(
C).

SPONSORS:
FMC
Corporation
SPONSOR
REPRESENTATIVE:
Nancy
J.
Hilton
Date
Product
Registrations
Manager
FMC
Corporation
FMC
Zeta­
cypermethrin
2004CROP.
rev
Page
3
GOOD
LABORATORY
PRACTICE
COMPLIANCE
STATEMENT
The
following
exposure
assessments
are
not
subject
to
the
principles
of
40
CFR
160,
GOOD
LABORATORY
PRACTICE
STANDARDS
(
FIFRA),
as
promulgated
in
Federal
Register,
54,
No.
158,
34067­
34704,
17
August
1989.
Several
studies
used
as
references
for
this
document
were
conducted
in
accordance
with
the
appropriate
GLP
standards
as
verified
by
the
GLP
compliance
statements
found
in
those
study
reports.

AUTHOR/
SPONSOR/
SUBMITTER:

Nancy
J.
Hilton
Date
Product
Registrations
Manager
FMC
Corporation
FMC
Zeta­
cypermethrin
2004CROP
Page
2
FQPA
Supplemental
Information
Document
for
Zeta­
Cypermethrin
EPA
Registration
Division
contact
George
T.
LaRocca.
(
703)
305­
6100.

1.
FMC
Corporation,
1735
Market
Street,
Philadelphia,
PA
19103.

PP
5F6896
EPA
has
received
pesticide
petition
(
PP
5F6896)
from
FMC
Corporation,
1735
Market
Street,
Philadelphia,
PA
19103,
proposing
pursuant
to
section
408
(
d)
of
the
Federal
Food,
Drug
and
Cosmetic
Act,
21
U.
S.
C.
346a(
d),
to
amend
40
C.
F.
R.
§
180.418
by
establishing
a
tolerance
for
residues
of
the
insecticide
zetacypermethrin
(_­_­
Cyano(
3­
phenoxyphenyl)
methyl
(_)
cis,
trans
3­(
2,2­
dichloroethenyl)­
2,2­
dimethylcyclopropanecarboxylate
and
its
inactive
isomers)
in
or
on
the
raw
agricultural
commodity
berries,
group
13,
0.5
ppm;
tree
nuts,
group
14,
nutmeat,
0.05
ppm,
and
hulls,
3.00
ppm;
grapes,
1.0
ppm,
grape,
juice,
0.05
ppm,
and
raisins,
0.20
ppm;
canola,
seed,
0.05
ppm,
canola,
meal,
0.05
ppm,
and
canola,
oil,
0.6
ppm;
nongrass
animal
feeds,
group
18,
forage,
10.00
ppm,
and
hay,
33.00
ppm;
grass
forage,
fodder,
and
hay,
group
17,
forage,
7.00
ppm,
hay,
22.00
ppm,
straw,
8.00
ppm,
and
seed
screenings,
12.00
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
1.
Plant
metabolism.
The
metabolism
of
cypermethrin
in
plants
is
adequately
understood.
Studies
have
been
conducted
to
delineate
the
metabolism
of
radiolabelled
cypermethrin
in
various
crops
all
showing
similar
results.
The
residue
of
concern
is
the
parent
compound
only.

2.
Analytical
method.
There
is
a
practical
analytical
method
for
detecting
and
measuring
levels
of
cypermethrin
in
or
on
food
with
a
limit
of
detection
that
allows
monitoring
of
food
with
residues
at
or
above
the
levels
set
in
these
tolerances
(
Gas
Chromatography
with
Electron
Capture
Detection
(
GC/
ECD).

3.
Magnitude
of
residues.
Crop
field
trial
residue
data
from
studies
conducted
at
the
maximum
label
rates
for
representative
commodities
for
the
berries
group,
tree
nuts
group,
grapes,
canola,
nongrass
animal
feeds
group,
and
grass
forage,
fodder
and
hay
group
show
that
the
proposed
zeta­
cypermethrin
tolerances
on
berries,
group
13,
at
0.5
ppm;
tree
nuts,
group
14,
nutmeat,
at
0.05
ppm,
and
hulls,
at
3.00
ppm;
grapes,
at
1.0
ppm,
grape,
juice,
at
0.05
ppm,
and
raisins,
at
0.20
ppm;
canola,
seed,
at
0.05
ppm,
canola,
meal,
at
0.05
ppm,
and
canola,
oil,
at
0.6
ppm;
nongrass
animal
feeds,
group
18,
forage,
at
10.00
ppm,
and
hay,
at
33.00
ppm;
grass
forage,
fodder,
and
hay,
group
17,
forage,
at
7.00
ppm,
hay,
at
22.00
ppm,
straw,
at
8.00
ppm,
and
seed
screenings,
at
12.00
ppm
will
not
be
exceeded
when
the
zeta­
cypermethrin
products
labeled
for
these
uses
are
used
as
directed.

B.
Toxicological
Profile
FMC
Zeta­
cypermethrin
2004CROP
Page
3
1.
Acute
toxicity.
For
the
purposes
of
assessing
acute
dietary
risk,
FMC
has
used
the
NOEL
of
10.0
mg/
kg/
day
from
the
zeta­
cypermethrin
acute
neurotoxicity
study
in
rats.
The
LOAEL
of
50.0
mg/
kg/
day
was
based
on
clinical
signs.
This
acute
dietary
endpoint
is
used
to
determine
acute
dietary
risks
to
all
population
subgroups.

2.
Genotoxicity.
The
following
genotoxicity
tests
were
all
negative:
in
vivo
chromosomal
aberration
in
rat
bone
marrow
cells;
in
vitro
cytogenic
chromosome
aberration;
unscheduled
DNA
synthesis;
CHO/
HGPTT
mutagen
assay;
weakly
mutagenic:
gene
mutation
(
Ames).

3.
Reproductive
and
developmental
toxicity.
No
evidence
of
additional
sensitivity
to
young
rats
was
observed
following
pre­
or
postnatal
exposure
to
zeta­
cypermethrin.
a.
A
two­
generation
reproductive
toxicity
study
with
zeta­
cypermethrin
in
rats
demonstrated
a
NOEL
of
7.0
mg/
kg/
day
and
a
LOEL
of
27.0
mg/
kg/
day
for
parental/
systemic
toxicity
based
on
body
weight,
organ
weight,
and
clinical
signs.
There
were
no
adverse
effects
in
reproductive
performance.
The
NOEL
for
reproductive
toxicity
was
considered
to
be
>
45.0
mg/
kg/
day
(
the
highest
dose
tested).
b.
A
developmental
study
with
zeta­
cypermethrin
in
rats
demonstrated
a
maternal
NOEL
of
12.5
mg/
kg/
day
and
a
LOEL
of
25
mg/
kg/
day
based
on
decreased
maternal
body
weight
gain,
food
consumption
and
clinical
signs.
There
were
no
signs
of
developmental
toxicity
at
35.0
mg/
kg/
day,
the
highest
dose
level
tested.
c.
A
developmental
study
with
cypermethrin
in
rabbits
demonstrated
a
maternal
NOEL
of
100
mg/
kg/
day
and
a
LOEL
of
450
mg/
kg/
day
based
on
decreased
body
weight
gain.
There
were
no
signs
of
developmental
toxicity
at
700
mg/
kg/
day,
the
highest
dose
level
tested.

4.
Subchronic
toxicity.
Short­
and
intermediate­
term
toxicity
(
incidental
oral
exposure).
The
NOEL
of
10.0
mg/
kg/
day
based
on
clinical
signs
at
the
LEL
of
50.0
mg/
kg/
day
in
the
zeta­
cypermethrin
acute
neurotoxicity
study
in
rats
would
also
be
used
for
short­
term
%
aPAD
and
MOE
calculations
(
as
well
as
acute,
discussed
in
(
1)
above),
and
the
NOEL
of
5.0
mg/
kg/
day
based
on
decreased
motor
activity
in
the
zeta­
cypermethrin
subchronic
neurotoxicity
study
in
rats,
would
be
used
for
intermediate­
term
MOE
calculations.

5.
Chronic
toxicity.
a.
The
chronic
reference
dose
(
RfD)
of
0.06
mg/
kg/
day
for
zeta­
cypermethrin
is
based
on
a
NOEL
of
6.0
mg/
kg/
day
from
a
cypermethrin
chronic
feeding
study
in
dogs
and
an
uncertainty
factor
of
100.
The
endpoint
effect
of
concern
was
based
on
clinical
signs.
b.
Cypermethrin
is
classified
as
a
Group
C
chemical
(
possible
human
carcinogen
with
limited
evidence
of
carcinogenicity
in
animals)
based
upon
limited
evidence
for
carcinogenicity
in
female
mice;
assignment
of
a
Q*
has
not
been
recommended.

6.
Animal
metabolism.
The
metabolism
of
cypermethrin
in
animals
is
adequately
understood.
Cypermethrin
has
been
shown
to
be
rapidly
absorbed,
distributed,
and
excreted
in
rats
when
administered
orally.
Cypermethrin
is
metabolized
by
hydrolysis
and
oxidation.

7.
Metabolite
toxicology.
The
Agency
has
previously
determined
that
the
metabolites
of
cypermethrin
are
not
of
toxicological
concern
and
need
not
be
included
in
the
tolerance
expression
nor
in
the
risk
exposure
assessments.

8.
Endocrine
Disruption.
No
special
studies
investigating
potential
estrogenic
or
other
endocrine
effects
of
cypermethrin
have
been
conducted.
However,
no
evidence
of
such
effects
were
reported
in
the
standard
battery
of
required
toxicology
studies
which
have
been
completed
and
found
acceptable.
Based
on
these
studies,
there
is
no
evidence
to
suggest
that
cypermethrin
has
an
adverse
effect
on
the
endocrine
system.

C.
Aggregate
Exposure
1.
Dietary
exposure.
a.
Food.
Permanent
tolerances,
in
support
of
registrations,
currently
exist
for
residues
of
zeta­
cypermethrin
on:
alfalfa
hay,
alfalfa
forage,
alfalfa
seed,
aspirated
grain
fractions,
sugar
beets
(
roots
and
tops),
head,
stem
and
leafy
Brassica
vegetables,
cabbage,
field
corn
grain,
pop
corn
grain,
field
corn
forage,
field
corn
stover,
pop
corn
stover,
sweet
corn
(
K+
CWHR),
sweet
corn
forage,
sweet
corn
FMC
Zeta­
cypermethrin
2004CROP
Page
4
stover,
cottonseed,
dried
shelled
peas
and
beans,
edible
podded
legume
vegetables,
fruiting
vegetables
(
except
Cucurbits),
leafy
vegetables,
head
lettuce,
bulb
and
green
onions,
pecans,
rice
grain,
rice
hulls,
rice
straw,
sorghum
forage,
sorghum
grain,
sorghum
stover,
soybean
seed,
succulent
shelled
peas
and
beans,
sugarcane,
wheat
forage,
wheat
grain,
wheat
hay,
wheat
straw,
meat,
fat
and
meat
byproducts
of
cattle,
goats,
hogs,
horses
and
poultry,
eggs,
milk
and
milk
fat.
For
the
purposes
of
assessing
the
potential
dietary
exposure
for
these
existing
and
the
subject
proposed
tolerances,
FMC
has
utilized
available
information
on
anticipated
residues,
monitoring
data
and
percent
crop
treated
as
follows:
i.
Acute
exposure
and
risk.
Acute
dietary
exposure
risk
assessments
are
performed
for
a
food­
use
pesticide
if
a
toxicological
study
has
indicated
the
possibility
of
an
effect
of
concern
occurring
as
a
result
of
a
one
day
or
single
exposure.
For
the
purposes
of
assessing
acute
dietary
risk
for
zeta­
cypermethrin,
FMC
has
used
the
NOEL
of
10.0
mg/
kg/
day
from
the
zeta­
cypermethrin
acute
neurotoxicity
study
in
rats
with
an
uncertainty
factor
(
UF)
of
100
(
acute
RfD
=
0.10
mg/
kg/
day).
The
LEL
of
50.0
mg/
kg/
day
was
based
on
clinical
signs.
This
acute
dietary
endpoint
is
used
to
determine
acute
dietary
risks
to
all
population
subgroups.
Available
information
on
anticipated
residues,
monitoring
data
and
percent
crop
treated
was
incorporated
into
a
Tier
3
analysis,
using
Monte
Carlo
modeling
for
commodities
that
may
be
consumed
in
a
single
serving.
These
assessments
show
that
the
percent
acute
Population
Adjusted
Dose
(%
aPAD)
all
fall
below
the
EPA's
level
of
concern
( 
100%).
The
95th
percentile
of
exposure
for
the
overall
U.
S.
population
was
estimated
to
be
0.002448
mg/
kg/
day
(%
aRfD
of
2.45);
99th
percentile
0.007176
mg/
kg/
day
(%
aRfD
of
7.18);
and
99.9th
percentile
0.024759
mg/
kg/
day
(%
aRfD
of
24.76).
The
95th
percentile
of
exposure
for
all
infants
(<
1
year)
was
estimated
to
be
0.005153
mg/
kg/
day
(%
aRfD
of
5.15);
99th
percentile
0.012833
mg/
kg/
day
(%
aRfD
of
12.83);
and
99.9th
percentile
0.035742
mg/
kg/
day
(%
aRfD
of
35.74).
The
95th
percentile
of
exposure
for
children
1
to
2
years
old
and
children
3
to
5
years
old
was
estimated
to
be,
respectively,
0.006932
mg/
kg/
day
(%
aRfD
of
6.93)
and
0.004758
mg/
kg/
day
(%
aRfD
of
4.76);
99th
percentile
0.016035
mg/
kg/
day
(%
aRfD
of
16.03)
and
0.011416
(%
aRfD
of
11.42);
and
99.9th
percentile
0.053308
mg/
kg/
day
(%
aRfD
of
53.31)
and
0.047651
(%
aRfD
of
47.65).
The
95th
percentile
of
exposure
for
females
(
13­
49
years)
was
estimated
to
be
0.001983
mg/
kg/
day
(%
aRfD
of
1.98);
99th
percentile
0.005391
mg/
kg/
day
(%
aRfD
of
5.39);
and
99.9th
percentile
0.020292
mg/
kg/
day
(%
aRfD
of
20.29).
Therefore,
FMC
concludes
that
the
acute
dietary
risk
of
zeta­
cypermethrin,
as
estimated
by
the
dietary
risk
assessment,
does
not
appear
to
be
of
concern.

Chronic
exposure
and
risk.
The
chronic
reference
dose
(
cRfD)
of
0.06
mg/
kg/
day
for
zeta­
cypermethrin
is
based
on
a
NOEL
of
6.0
mg/
kg/
day
from
a
cypermethrin
chronic
feeding
study
in
dogs
and
an
uncertainty
factor
of
100.
The
endpoint
effect
of
concern
was
based
on
clinical
signs.
A
chronic
dietary
exposure/
risk
assessment
has
been
performed
for
zeta­
cypermethrin
using
the
above
cRfD.
Available
information
on
anticipated
residues,
monitoring
data
and
percent
crop
treated
was
incorporated
into
the
analysis
to
estimate
the
anticipated
residue
contribution
(
ARC).
The
ARC
is
generally
considered
a
more
realistic
estimate
than
an
estimate
based
on
tolerance
level
residues.
The
ARC
are
estimated
to
be
0.000958
mg/
kg
body
weight
(
bwt)/
day
and
utilize
1.6
percent
of
the
cRfD
for
the
overall
U.
S.
population.
The
ARC
for
all
infants
(<
1
year)
are
estimated
to
be
0.001486
mg/
kg
bwt/
day
and
utilizes
2.5
percent
of
the
cRfD.
The
ARC
for
children
1
to
2
years
old
and
children
3
to
5
years
old
are
estimated
to
be
0.003881
mg/
kg
bwt/
day
and
0.002680
mg/
kg
bwt/
day
and
utilizes
6.5
percent
and
4.5
percent
of
the
cRfD,
respectively.
The
ARC
for
females
(
13­
49
years)
is
estimated
to
be
0.000631
mg/
kg
bwt/
day
and
utilizes
1.1
percent
of
the
RfD.
Generally
speaking,
the
EPA
has
no
cause
for
concern
if
the
total
dietary
exposure
from
residues
for
uses
for
which
there
are
published
and
proposed
tolerances
is
less
than
100
percent
of
the
cRfD.
Therefore,
FMC
concludes
that
the
chronic
dietary
risk
of
zeta­
cypermethrin,
as
estimated
by
the
dietary
risk
assessment,
does
not
appear
to
be
of
concern.

Drinking
water.
Laboratory
and
field
data
have
demonstrated
that
cypermethrin
is
immobile
in
soil
and
will
not
leach
into
groundwater.
Other
data
show
that
cypermethrin
is
virtually
insoluble
in
water
and
extremely
lipophilic.
As
a
result,
FMC
concludes
that
residues
reaching
surface
waters
from
field
runoff
will
quickly
adsorb
to
sediment
particles
and
be
partitioned
from
the
water
column.
Drinking
water
estimated
concentrations
(
DWEC)
and
the
corresponding
drinking
water
level
of
comparison
(
DWLOC)
values
were
calculated
for
chronic
and
acute
exposures.
The
results
show
that
all
DWLOC
values
exceed
the
DWEC
values.
Thus,
exposure
to
zetacypermethrin
and
cypermethrin
residues
in
drinking
water
is
not
of
concern.
FMC
Zeta­
cypermethrin
2004CROP
Page
5
US
EPA's
draft
SOP
for
Incorporating
Estimates
of
Drinking
Water
Exposure
Into
Aggregate
Risk
Assessments
was
used
to
perform
a
drinking
water
analysis.
This
SOP
utilizes
a
variety
of
tools
to
conduct
drinking
water
assessment.
These
tools
include
water
models
such
as
FQPA
Index
Reservoir
Screening
Tool
(
FIRST),
PRZM/
EXAMS,
SCIGROW
and
monitoring
data.
If
monitoring
data
are
not
available
then
the
models
are
used
to
predict
potential
residues
in
drinking
water.
The
technique
recommended
in
the
drinking
water
SOP
compares
a
calculated
Drinking
Water
Level
of
Comparison
(
DWLOC)
value
to
the
Drinking
Water
Estimated
Concentration
(
DWEC)
value.
The
DWEC
value
results
from
either
the
monitoring
data
residues
or
modeled
water
residues.
If
the
DWLOC
value
exceeds
the
DWEC
value
then
there
is
reasonable
certainty
that
no
harm
will
result
from
the
acute
or
chronic
aggregate
exposure.

In
the
case
of
cypermethrin
and
zetacypermethrin,
monitoring
data
do
not
exist.
Therefore,
the
FIRST
model
was
used
to
estimate
a
surface
water
residue.
The
risk
assessment
for
drinking
water
compares
two
values:
the
DWLOC
and
the
DWEC.
The
DWLOC
is
the
drinking
water
level
of
comparison.
This
is
the
maximum
allowable
drinking
water
concentration
(
in
ppb).
The
DWEC
is
the
drinking
water
environmental
concentration,
which
is
derived
either
from
monitoring
studies
or
from
modeling.
If
the
DWLOC
is
greater
than
the
DWEC,
then
the
overall
exposure
from
water,
food,
and
residential
is
considered
to
be
acceptable.
The
calculated
DWLOC
values
for
acute
and
chronic
exposures
for
all
adults,
adult
females
and
children
exceed
the
modeled
DWEC
surface
water
residues.
Therefore,
there
is
reasonable
certainty
that
no
harm
will
result
from
cumulative
and
aggregate
(
food
and
water)
exposure
to
cypermethrin
and
zetacypermethrin
residues.

2.
Non­
dietary
exposure.
Zeta­
cypermethrin
is
registered
for
agricultural
crop
applications
only,
therefore
nondietary
exposure
assessments
are
not
warranted.

D.
Cumulative
Effects.
In
consideration
of
potential
cumulative
effects
of
cypermethrin
and
other
substances
that
may
have
a
common
mechanism
of
toxicity,
to
our
knowledge
there
are
currently
no
available
data
or
other
reliable
information
indicating
that
any
toxic
effects
produced
by
cypermethrin
would
be
cumulative
with
those
of
other
chemical
compounds;
thus
only
the
potential
risks
of
cypermethrin
have
been
considered
in
this
assessment
of
its
aggregate
exposure.
FMC
intends
to
submit
information
for
the
EPA
to
consider
concerning
potential
cumulative
effects
of
cypermethrin
consistent
with
the
schedule
established
by
EPA
at
62
Federal
Register
42020
(
August
4,
1997)
and
other
EPA
publications
pursuant
to
the
Food
Quality
Protection
Act.
FMC
Zeta­
cypermethrin
2004CROP
Page
6
E.
Safety
Determination
1.
U.
S.
population.
The
chronic
reference
dose
(
cRfD)
of
0.06
mg/
kg/
day
for
zeta­
cypermethrin
is
based
on
a
NOEL
of
6.0
mg/
kg/
day
from
a
cypermethrin
chronic
feeding
study
in
dogs
and
an
uncertainty
factor
of
100.
The
endpoint
effect
of
concern
was
based
on
clinical
signs.
A
chronic
dietary
exposure/
risk
assessment
has
been
performed
for
zeta­
cypermethrin
using
the
above
cRfD.
Available
information
on
anticipated
residues,
monitoring
data
and
percent
crop
treated
was
incorporated
into
the
analysis
to
estimate
the
anticipated
residue
contribution
(
ARC).
The
ARC
is
generally
considered
a
more
realistic
estimate
than
an
estimate
based
on
tolerance
level
residues.
The
ARC
are
estimated
to
be
0.000958
mg/
kg
body
weight
(
bwt)/
day
and
utilize
1.6
percent
of
the
cRfD
for
the
overall
U.
S.
population.
The
ARC
for
all
infants
(<
1
year)
are
estimated
to
be
0.001486
mg/
kg
bwt/
day
and
utilizes
2.5
percent
of
the
cRfD.
The
ARC
for
children
1
to
2
years
old
and
children
3
to
5
years
old
are
estimated
to
be
0.003881
mg/
kg
bwt/
day
and
0.002680
mg/
kg
bwt/
day
and
utilizes
6.5
percent
and
4.5
percent
of
the
cRfD,
respectively.
The
ARC
for
females
(
13­
49
years)
is
estimated
to
be
0.000631
mg/
kg
bwt/
day
and
utilizes
1.1
percent
of
the
RfD.
Generally
speaking,
the
EPA
has
no
cause
for
concern
if
the
total
dietary
exposure
from
residues
for
uses
for
which
there
are
published
and
proposed
tolerances
is
less
than
100
percent
of
the
cRfD.
Therefore,
FMC
concludes
that
the
chronic
dietary
risk
of
zeta­
cypermethrin,
as
estimated
by
the
dietary
risk
assessment,
does
not
appear
to
be
of
concern.

Acute
dietary
exposure
risk
assessments
are
performed
for
a
food­
use
pesticide
if
a
toxicological
study
has
indicated
the
possibility
of
an
effect
of
concern
occurring
as
a
result
of
a
one
day
or
single
exposure.
For
the
purposes
of
assessing
acute
dietary
risk
for
zeta­
cypermethrin,
FMC
has
used
the
NOEL
of
10.0
mg/
kg/
day
from
the
zeta­
cypermethrin
acute
neurotoxicity
study
in
rats
with
an
uncertainty
factor
(
UF)
of
100
(
acute
RfD
=
0.10
mg/
kg/
day).
The
LEL
of
50.0
mg/
kg/
day
was
based
on
clinical
signs.
This
acute
dietary
endpoint
is
used
to
determine
acute
dietary
risks
to
all
population
subgroups.
Available
information
on
anticipated
residues,
monitoring
data
and
percent
crop
treated
was
incorporated
into
a
Tier
3
analysis,
using
Monte
Carlo
modeling
for
commodities
that
may
be
consumed
in
a
single
serving.
These
assessments
show
that
the
percent
acute
Population
Adjusted
Dose
(%
aPAD)
all
fall
below
the
EPA's
level
of
concern
( 
100%).
The
95th
percentile
of
exposure
for
the
overall
U.
S.
population
was
estimated
to
be
0.002448
mg/
kg/
day
(%
aRfD
of
2.45);
99th
percentile
0.007176
mg/
kg/
day
(%
aRfD
of
7.18);
and
99.9th
percentile
0.024759
mg/
kg/
day
(%
aRfD
of
24.76).
The
95th
percentile
of
exposure
for
all
infants
(<
1
year)
was
estimated
to
be
0.005153
mg/
kg/
day
(%
aRfD
of
5.15);
99th
percentile
0.012833
mg/
kg/
day
(%
aRfD
of
12.83);
and
99.9th
percentile
0.035742
mg/
kg/
day
(%
aRfD
of
35.74).
The
95th
percentile
of
exposure
for
children
1
to
2
years
old
and
children
3
to
5
years
old
was
estimated
to
be,
respectively,
0.006932
mg/
kg/
day
(%
aRfD
of
6.93)
and
0.004758
mg/
kg/
day
(%
aRfD
of
4.76);
99th
percentile
0.016035
mg/
kg/
day
(%
aRfD
of
16.03)
and
0.011416
(%
aRfD
of
11.42);
and
99.9th
percentile
0.053308
mg/
kg/
day
(%
aRfD
of
53.31)
and
0.047651
(%
aRfD
of
47.65).
The
95th
percentile
of
exposure
for
females
(
13­
49
years)
was
estimated
to
be
0.001983
mg/
kg/
day
(%
aRfD
of
1.98);
99th
percentile
0.005391
mg/
kg/
day
(%
aRfD
of
5.39);
and
99.9th
percentile
0.020292
mg/
kg/
day
(%
aRfD
of
20.29).
Therefore,
FMC
concludes
that
the
acute
dietary
risk
of
zeta­
cypermethrin,
as
estimated
by
the
dietary
risk
assessment,
does
not
appear
to
be
of
concern.

2.
Infants
and
children.
a.
General.
In
assessing
the
potential
for
additional
sensitivity
of
infants
and
children
to
residues
of
zeta­
cypermethrin,
FMC
considered
data
from
developmental
toxicity
studies
in
the
rat
and
rabbit,
and
a
two­
generation
reproductive
study
in
the
rat.
The
data
demonstrated
no
indication
of
increased
sensitivity
of
rats
to
zeta­
cypermethrin
or
rabbits
to
cypermethrin
in
utero
and/
or
postnatal
exposure
to
zeta­
cypermethrin
or
cypermethrin.
The
developmental
toxicity
studies
are
designed
to
evaluate
adverse
effects
on
the
developing
organism
resulting
from
pesticide
exposure
during
prenatal
development
to
one
or
both
parents.
Reproduction
studies
provide
information
relating
to
effects
from
exposure
to
the
pesticide
on
the
reproductive
capability
of
mating
animals
and
data
on
systemic
toxicity.
FFDCA
section
408
provides
that
EPA
may
apply
an
additional
margin
of
safety
for
infants
and
children
in
the
case
of
threshold
effects
to
account
for
pre­
and
post­
natal
toxicity
and
the
completeness
of
the
database.
b.
Developmental
toxicity
studies.
In
the
prenatal
developmental
toxicity
studies
in
rats
and
rabbits,
there
was
no
evidence
of
developmental
toxicity
at
the
highest
doses
tested
(
35.0
mg/
kg/
day
in
rats
and
700
FMC
Zeta­
cypermethrin
2004CROP
Page
7
mg/
kg/
day
in
rabbits).
Decreased
body
weight
gain
was
observed
at
the
maternal
LOEL
in
each
study;
the
maternal
NOEL
was
established
at
12.5
mg/
kg/
day
in
rats
and
100
mg/
kg/
day
in
rabbits.
c.
Reproductive
toxicity
study.
In
the
two­
generation
reproduction
study
in
rats,
offspring
toxicity
(
body
weight)
and
parental
toxicity
(
body
weight,
organ
weight,
and
clinical
signs)
was
observed
at
27.0
mg/
kg/
day
and
greater.
The
parental
systemic
NOEL
was
7.0
mg/
kg/
day
and
the
parental
systemic
LOEL
was
27.0
mg/
kg/
day.
There
were
no
developmental
(
pup)
or
reproductive
effects
up
to
45.0
mg/
kg/
day,
highest
dose
tested.
d.
Pre­
and
post­
natal
sensitivity.
i.
Pre­
natal.
There
was
no
evidence
of
developmental
toxicity
in
the
studies
at
the
highest
doses
tested
in
the
rat
(
70.0
mg/
kg/
day)
or
in
the
rabbit
(
700
mg/
kg/
day).
Therefore,
there
is
no
evidence
of
a
special
dietary
risk
(
either
acute
or
chronic)
for
infants
and
children
which
would
require
an
additional
safety
factor.
ii.
Post­
natal.
Post­
natal.
Based
on
the
absence
of
pup
toxicity
up
to
dose
levels
which
produced
toxicity
in
the
parental
animals,
there
is
no
evidence
of
special
post­
natal
sensitivity
to
infants
and
children
in
the
rat
reproduction
study.
e.
Conclusion.
Based
on
the
above,
FMC
concludes
that
reliable
data
support
use
of
the
standard
100­
fold
uncertainty
factor,
and
that
an
additional
uncertainty
factor
is
not
needed
to
protect
the
safety
of
infants
and
children.
As
stated
above,
aggregate
exposure
assessments
utilized
significantly
less
than
1
percent
of
the
RfD
for
either
the
entire
U.
S.
population
or
any
of
the
26
population
subgroups
including
infants
and
children.
Therefore,
it
may
be
concluded
that
there
is
reasonable
certainty
that
no
harm
will
result
to
infants
and
children
from
aggregate
exposure
to
cypermethrin
residues.

F.
International
Tolerances.
There
are
no
Canadian,
or
Mexican
residue
limits
for
residues
of
cypermethrin
or
zeta­
cypermethrin
in
or
on
representative
commodities
for
the
berries
group,
tree
nuts
group,
grapes,
canola,
nongrass
animal
feeds
group,
and
grass
forage,
fodder
and
hay
group.

The
Codex
MRLs
for
cypermethrin
are
0.5
ppm
for
berries
and
other
small
fruit,
0.2
ppm
for
oilseed,
except
peanut,
and
0.5
ppm
for
vegetable
oils,
edible.
