Document ID: EPA-HQ-OPP-2006-0730-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-09-13T04:00Z

1
EPA
Registration
Division
contact:
By
Mail:
George
T.
LaRocca,
Product
Manager
(
PM)
13,
Registration
Division
(
7505C),
Environmental
Protection
Agency,
401
M
St.,
SW.,
Washington,
DC
20460.
Office
location
and
telephone
number:
CM
2,
1921
Jefferson
Davis
Hwy.,
Arlington,
VA
22202,
(
703)­
305­
6100;
e­
mail:
larocca.
george@
epa.
gov
Interregional
Research
Project
Number
4
(
IR­
4)

IR­
4
P.
R.
No.

EPA
has
received
a
pesticide
petition
(
IR­
4
P.
R.
No.)
from
Interregional
Research
Project
Number
4
(
IR­
4),
681
U.
S.
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
180.533
by
establishing
a
national
tolerance
for
residues
of
the
insecticide,
esfenvalerate
((
S)­
cyano­(
3­
phenoxyphenyl)
methyl(
S)­
4­
chloro­
alpha­(
1­
methylethyl)
benzeneacetate)
in
or
on
okra
at
0.5
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.
This
notice
includes
a
summary
of
the
petitions
prepared
by
DuPont
Crop
Protection,(
formerly
DuPont
Agricultural
Products),
P.
O.
Box
30,
Newark,
DE
19714­
0030.

A.
Residue
Chemistry
1.
Plant
metabolism.
The
metabolism
and
chemical
nature
of
residues
of
fenvalerate
in
plants
and
animals
are
adequately
understood.
The
fate
of
fenvalerate
has
been
extensively
studied
using
radioactive
tracers
in
plant
and
animal
metabolism/
nature
of
the
residue
studies.
These
studies
have
demonstrated
that
the
parent
compound
is
the
only
residue
of
toxicological
significance.
EPA
has
concluded
that
the
qualitative
nature
of
the
residue
is
the
same
for
both
fenvalerate
and
esfenvalerate.

2.
Analytical
method.
There
is
a
practical
analytical
method
utilizing
electron­
capture
gas
chromatography
with
nitrogen
phosphorous
detection
available
for
enforcement
with
a
limit
of
detection
that
allows
monitoring
food
with
residues
at
or
above
tolerance
levels.
The
limit
of
detection
for
updated
method
is
the
same
as
that
of
the
current
PAM
II,
which
is
0.01
ppm.

3.
Magnitude
of
residues.
Fenvalerate
is
a
racemic
mixture
of
four
isomers
about
25%
each.
Technical
Asana
®
,
the
S,
S­
isomer
enriched
formulation,
esfenvalerate,
has
been
the
only
fenvalerate
formulation
sold
in
the
U.
S.
for
agricultural
use.
Since
the
S,
S­
isomer
is
the
insecticidally
active
isomer,
the
use
rate
for
Asana
®
is
4
times
lower
than
that
for
Pydrin
®
.
A
2
petition
is
pending
(
PP
4F4329),
to
convert
tolerances
still
to
be
expressed
as
the
sum
of
all
isomers
based
on
the
use
rates
for
Asana
®
.
Bridging
residue
studies
have
shown
Asana
®
residues
to
be
3­
4
times
lower
than
Pydrin
®
residues.
Field
trials
were
conducted
on
okra
and
a
regional
tolerance
was
previously
established
for
fenvalerate
at
0.1
ppm.
No
data
was
submitted
in
support
of
this
petition;
rather,
IR­
4
proposes
that
EPA
utilizes
the
registrant's
fruiting
vegetable
data
(
peppers
and
tomatoes)
to
establish
a
tolerance
for
esfenvalerate
at
0.5
ppm.
IR­
4
believes
this
approach
is
justified
based
upon
the
similarities
of
okra
to
members
of
the
fruiting
vegetable
crop
group.
It
is
noteworthy
that
okra
is
classified
as
a
fruiting
vegetable
under
CODEX.

B.
Toxicological
Profile
As
assessment
of
the
toxic
effects
caused
by
esfenvalerate
is
discussed
in
Unit
III.
A.
and
Unit
III.
B.
of
the
Federal
Register
dated
March
1,
2001
(
66
FR
16926)
(
FRL­
6774­
5).

1.
Animal
metabolism.
In
animal
studies,
after
oral
dosing
with
radioactive
fenvalerate,
the
majority
of
the
administered
radioactivity
was
eliminated
in
the
initial
24­
hours.
The
metabolic
pathway
involved
cleavage
of
the
ester
linkage
followed
by
hydroxylation,
oxidation,
and
conjugation
of
the
acid
and
alcohol
moieties.

2.
Metabolite
toxicology.
The
parent
molecule
is
the
only
moiety
of
toxicological
significance
appropriate
for
regulation
in
plant
and
animal
commodities.

C.
Aggregate
Exposure
1.
Dietary
exposure.
Tolerances
have
been
established
for
the
residues
of
fenvalerate/
esfenvalerate,
in
or
on
a
variety
of
agricultural
commodities.
For
purposes
of
assessing
dietary
exposure,
chronic
and
acute
dietary
assessments
have
been
conducted
using
all
existing
registered
uses
for
esfenvalerate,
including
okra,
peppers
and
tomatoes.
The
following
crops
with
pending
petitions
have
been
included
in
the
assessment:
Brussels
sprouts;
cabbage,
Chinese,
bok
choy;
canola;
cardoon;
sweet
potato,
and
pistachio.
In
addition,
previously
pending
or
intended
uses
that
have
been
withdrawn
(
leaf
lettuce,
kale,
passion
fruit)
are
also
included
in
the
dietary
exposure
assessment.

i.
Food.
a.
Chronic.
A
chronic
dietary
exposure
assessment
was
conducted
using
Novigen's
Dietary
Exposure
Estimate
Model
(
DEEM
®
)
.
Anticipated
residues
and
adjustment
for
percent
crop
treated
were
used
in
the
chronic
dietary
risk
assessment.
The
percentages
of
the
reference
dose
(
RfD)
utilized
by
the
most
sensitive
subpopulation,
children
1­
6
years,
was
2.0%
based
on
a
daily
dietary
exposure
of
0.000134
milligrams/
kilogram
body
weight/
day
(
mg/
kg
bwt/
day).
Chronic
exposure
for
the
overall
US
population
was
0.9%
of
the
RfD
based
on
a
dietary
exposure
of
0.000058
mg/
kg
bw/
day.
EPA
has
no
concern
for
exposures
below
100%
of
the
RfD
because
the
RfD
represents
the
level
at
or
below
which
daily
aggregate
dietary
exposure
3
over
a
lifetime
will
not
pose
appreciable
risks
to
human
health.
b.
Acute
exposure.
Potential
acute
exposures
from
food
commodities
were
estimated
using
a
Tier
3
(
Monte
Carlo)
Analysis,
appropriate
processing
factors
for
processed
food,
and
distribution
analysis.
This
analysis
used
data
from
field
trial
studies
and
pesticide
monitoring
programs
to
estimate
exposure,
and
federal
and
market
survey
information
to
derive
the
percent
of
crop
treated.
These
data
are
considered
reliable,
and
used
the
upper
end
estimate
of
percent
crop
treated
in
order
to
not
underestimate
any
significant
subpopulation.
Regional
consumption
information
was
taken
into
account.

ii.
Drinking
water.
Esfenvalerate
is
immobile
in
soil
and
will
not
leach
into
ground
water.
Due
to
the
insolubility
and
lipophilic
nature
of
esfenvalerate,
any
residues
in
surface
water
will
rapidly
and
tightly
bind
to
soil
particles
and
remain
with
sediment,
therefore
not
contributing
to
potential
dietary
exposure
from
drinking
water.
Surface
water
concentrations
for
pyrethroids
were
estimated
using
PRZM3
and
Exposure
Analysis
Modeling
System
(
EXAMS)
using
Standard
EPA
cotton
runoff
and
Mississippi
pond
scenarios.
The
maximum
concentration
predicted
in
the
simulated
pond
was
0.052
parts
per
billion
(
ppb).
Concentrations
in
actual
drinking
water
would
be
much
lower
than
the
levels
predicted
in
the
hypothetical,
small,
stagnant
farm
pond
model
since
drinking
water
derived
from
surface
water
would
be
treated
before
consumption.
Chronic
drinking
water
exposure
has
been
estimated
to
be
0.000001
mg/
kg/
day
for
both
the
U.
S.
general
population
and
for
non­
nursing
infants.
Therefore,
DuPont
believes
that
there
is
a
reasonable
certainty
of
no
harm
from
drinking
water.

2.
Non­
dietary
exposure.
Esfenvalerate
is
registered
for
non­
crop
uses
including
spray
treatments
in
and
around
commercial
and
residential
areas,
treatments
for
control
of
ectoparasites
on
pets,
home
care
products
including
foggers,
pressurized
sprays,
crack
and
crevice
treatments,
lawn
and
garden
sprays,
and
pet
and
pet
bedding
sprays.
For
the
non­
agricultural
products,
the
very
low
amounts
of
active
ingredient
they
contain,
combined
with
the
low
vapor
pressure
(
1.5
x
10­
9
mm
Mercury
at
25
deg.
C.)
and
low
dermal
penetration,
would
result
in
minimal
inhalation
and
dermal
exposure.
To
assess
risk
from
nonfood
short­
term
and
intermediate­
term
exposure,
EPA
has
selected
a
toxicological
endpoint
of
2.0
mg/
kg/
day,
the
NOAEL
from
the
rat
and
rabbit
developmental
studies.
For
dermal
penetration/
absorption,
EPA
selected
25%
dermal
absorption
based
on
the
weight­
of­
evidence
available
for
structurally
related
pyrethroids.
For
inhalation
exposure,
EPA
used
the
oral
NOAEL
of
2.0
mg/
kg/
day
and
assumed
100%
absorption
by
inhalation.
Individual
non­
dietary
risk
exposure
analyses
were
conducted
using
a
flea
infestation
scenario
that
included
pet
spray,
carpet
and
room
treatment,
and
lawn
care,
respectively.
The
total
potential
short­
term
and
intermediate­
term
aggregate
non­
dietary
exposure
including
lawn,
carpet,
and
pet
uses
are:
0.000023
mg/
kg/
day
for
adults,
0.00129
mg/
kg/
day
for
children
1­
6
years
old,
and
0.00138
mg/
kg/
day
for
infants
less
than
1­
year
old.
EPA
concluded
in
a
final
rule
published
in
the
Federal
Register
of
November
26,
1997
(
62
FR
63019)
(
FRL­
5754­
6)
that
the
potential
non­
dietary
exposure
for
esfenvalerate
is
associated
with
4
substantial
margins
of
safety,
and
that
there
was
reasonable
certainty
that
no
harm
will
result
from
aggregate
exposure
to
esfenvalerate
residues.

D.
Cumulative
Effects
Section
408
(
b)
(
2)
(
D)
(
v)
requires
that,
when
considering
whether
to
establish,
modify,
or
revoke
a
tolerance,
the
Agency
consider
  
available
information''
concerning
the
cumulative
effects
of
a
particular
pesticide's
residues
and
  
other
substances
that
have
a
common
mechanism
of
toxicity''.
EPA
does
not
have
at
this
time
available
data
to
determine
whether
esfenvalerate
has
a
common
method
of
toxicity
with
other
substances,
or
how
to
include
this
pesticide
in
a
cumulative
risk
assessment.
Unlike
other
pesticides
for
which
EPA
has
followed
a
cumulative
risk
approach
based
on
a
common
mechanism
of
toxicity,
esfenvalerate
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
esfenvalerate
has
a
common
mechanism
of
toxicity
with
other
substances.

E.
Safety
Determination
1.
U.
S.
population.
Based
on
the
chronic
dietary
exposure
assessment,
it
is
concluded
that
exposure
to
esfenvalerate,
including
the
proposed
uses
in
food
will
utilize
approximately
0.9%
of
the
RfD
for
the
U.
S.
general
population.
There
is
generally
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.
The
margin
of
exposure
(
MOE)
for
the
general
population
was
472
at
the
99.9th
percentile
of
exposure,
based
on
a
daily
exposure
estimate
of
0.004229
mg/
kg
bwt/
day.
Therefore,
there
is
a
reasonable
certainty
that
no
harm
to
the
U.
S.
population
will
result
from
chronic
dietary,
acute
dietary,
non­
dietary,
or
aggregate
exposure
to
esfenvalerate
residues.

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
prenatal
and
postnatal
effects,
and
the
completeness
of
the
toxicity
data
base.
An
extra
3X
safety
factor
has
been
assessed
for
esfenvalerate
due
to
a
data
gap.
A
chronic
dietary
exposure
assessment
found
the
percentages
of
the
RfD
utilized
by
the
most
sensitive
subpopulation
to
be
2.0%
for
children
1­
6
years
old
based
on
a
dietary
exposure
of
0.000134
mg/
kg
bw/
day.
The
most
sensitive
subpopulation,
children
1­
6
years,
had
acute
dietary
MOE
of
378
at
the
99.9th
percentile
of
exposure.
Nursing
infants
had
a
MOE
of
750
at
the
99.9th
percentile
of
exposure.
Non­
nursing
infants
had
a
MOE
of
761at
the
99.9th
percentile
of
exposure.
Therefore,
there
is
a
reasonable
certainty
that
no
harm
to
infants
and
children
will
result
from
chronic
dietary,
acute
dietary,
non­
dietary,
or
aggregate
exposure
to
esfenvalerate
residues.
5
F.
International
Tolerances
Codex
maximum
residue
levels
(
MRL's)
have
been
established
for
residues
of
fenvalerate
on
a
number
of
crops
that
also
have
U.
S.
tolerances.
There
are
some
minimal
differences
between
the
section
408
tolerances
and
certain
Codex
MRL
values
for
specific
commodities.
These
differences
could
be
caused
by
differences
in
methods
to
establish
tolerances,
calculate
animal
feed,
dietary
exposure,
and
as
a
result
of
different
agricultural
practices.
Therefore,
some
harmonization
of
these
maximum
residue
levels
may
be
required.