Document ID: EPA-HQ-OPP-2009-1008-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-03-19T04:00Z

EPA Registration Division contact: Laura Nollen	

Interregional Research Project Number 4 (IR-4)

Petition Number 9E7652

(2-methyl [1,1′-biphenyl]-3-yl)
methyl-3-(2-chloro-3,3,3,-trifluoro-1-propenyl)-2,2-dimethylcyclopropane
carboxylate), in or on tea at 25 ppm (import tolerance); and tolerances
with regional registrations in or on grass, forage at 2.5 ppm; and
grass, hay at 4.5 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.

A. Residue Chemistry              

                        

		1. Plant metabolism. The metabolism of bifenthrin in plants is
adequately understood. Studies have been conducted to delineate the
metabolism of radiolabelled bifenthrin 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 bifenthrin 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. Field residue trials meeting EPA study
requirements have been conducted at the maximum label rate for the crops
blueberries and celery.  Results from the studies demonstrate that the
highest bifenthrin residues found will not exceed the proposed
tolerances for Tea at 25 ppm,  Grass, forage at 2.5 ppm, and Grass, hay
at 4.5 ppm when bifenthrin is applied following the proposed use
directions.

B. Toxicological Profile

		1. Acute toxicity.  For the purposes of assessing acute dietary risk,
FMC has used the results of the 2003 EPA completed risk assessment for
bifenthrin. This acute dietary endpoint  used to determine acute dietary
risks to the general population including infants and children is from
the acute neurotoxicity study in rats, (LOAEL) = 70.3 mg -/kg/day, NOAEL
= 32.8 mg -/kg/day, UF = 1000, Acute RfD = 0.033 mg/kg/day.

		2. Genotoxicty.  The mouse lymphoma mutagenesis assay gave a weak
positive result; however, the weight of the evidence from short-term
mutagenicity tests indicate that bifenthrin is not mutagenic.

		3. Reproductive and developmental toxicity.  i. Rat reproduction
study.  Parental toxicity occurred as decreased body weight at 5.0
mg/kg/day with a no observed adverse effect level (NOAEL) of 3.0
mg/kg/day.  There were no developmental (pup) or reproductive effects up
to 5.0 mg/kg/day (highest dose tested).

ii. Postnatal Sensitivity.  Based on the absence of pup toxicity up to
dose levels, which produced toxicity in the parental animals, there was
no evidence of special postnatal sensitivity to infants and children in
the rat reproduction study.  In a developmental neurotoxicity study,
pups were not more sensitive than the dams.  The NOAELs for maternal and
developmental neurotoxicity were both 50 ppm.

		4. Subchronic toxicity. The results of the 21-day dermal toxicity
study in rats is used for short-term (1-30 days), intermediate-term (1-6
months) and long-term (> 6 months) dermal risk calculations.  The 21-day
dermal toxicity study NOAEL for systemic toxicity is 47 mg ai/kg/day
based on observations of clinical signs (exaggerated hindlimb flexion
and staggered gait).

		5. Chronic toxicity. The reference dose (RfD) has been established at
0.004 mg/kg/day.  This RfD is based on a one-year oral study in dogs
with a LOAEL of 2.7 mg /kg/day and a NOAEL of 1.3  mg /kg/day, UF = 300
based on observations of increased incidence of tremors in both sexes. 

ii. Bifenthrin is classified as a Group C chemical (possible human
carcinogen); No Q1* has been derived.

		6. Animal metabolism. The metabolism of bifenthrin in animals is
adequately understood.  Metabolism studies in rats with single doses
demonstrated that about 90% of the parent compound and its hydroxylated
metabolites are excreted.

		7. Metabolite toxicology. The Agency has previously determined that
the metabolites of bifenthrin are not of toxicological concern and need
not be included in the tolerance expression.

		8. Endocrine disruption.  No special studies investigating potential
estrogenic or other endocrine effects of bifenthrin have been conducted.
 However, no evidence of such effects was 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 bifenthrin has an adverse effect on the endocrine system..

C. Aggregate Exposure

		1. Dietary exposure. Tolerances have been established for the residues
of bifenthrin, in or on a variety of raw agricultural commodities. 
Tolerances, in support of registrations, currently exist for residues of
bifenthrin on the following crops: hops, strawberries, corn (grain,
forage and fodder), sweet corn, eggplant, cottonseed, artichokes,
peppers (bell and non-bell), lettuce (head), grapes, spinach, cabbage,
rapeseed, tomatoes, Food Handling Establishments, banana (import),
pears, okra, cilantro, mayhaw, peanut, and soybeans.  Also for the crop
groups: vegetables, cucurbit, group 9, fruit, citrus, group 10 and nuts,
tree, group 14, fruiting vegetables, group 8 and the subgroups:
vegetable, legume, edible podded, subgroup 6A, pea and bean, succulent
shelled, subgroup 6B, caneberry subgroup 13A, and brassica, head and
stem, subgroup 5A, herb subgroup 19A, leaf petioles subgroup 4B,
vegetables tuberous and corm, subgroup 1C, pea and bean, dried shelled,
except soybeans, subgroup 6C, root crops, subgroup 1B, bushberries,
subgroup 13B.  Also, for the livestock commodities of cattle, goats,
hogs, horses, sheep, poultry, eggs, and milk.  For the purposes of
assessing the potential dietary exposure for these existing and pending
tolerances, EPA conducted an exposure estimate using Dietary Exposure
Evaluation Model – Food Commodity Intake Database TM (DEEM-FCIDTM)
Version 2.14, results from field trials and processing studies,
monitoring data, consumption data from the 1989-1992, USDA Continuing
Surveys of Food Intakes by Individuals (CSFII), and information on the
percentages of the crops treated (where available) with bifenthrin were
utilized.

		i. Food.  a. 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 1-day or
single exposure.  For the purposes of assessing acute dietary risk, FMC
has used the results of the 2003 EPA completed risk assessment for
bifenthrin. This acute dietary endpoint  used to determine acute dietary
risks to the general population including infants and children is from
the acute neurotoxicity study in rats, LOAEL= 70.3 mg/kg/day, NOAEL =
32.8 mg /kg/day, UF = 100, Acute RfD = 0.328 mg/kg/day.   Assumptions of
tolerance-level residues and 100 percent crop treated were incorporated
into a Tier I analysis. The 95th percentile of exposure for the general
U.S. Population is estimated to be 0.0127 mg/kg/day (3.88% aPAD).  The
95th percentile of exposure for infants <1 year old (most highly exposed
population subgroup) is estimated to be 0.0256 mg/kg/day (7.80% aPAD). 
The 95th percentile of exposure to children 3-5 years old is estimated
to be 0.0152 mg/kg/day (4.64% aPAD).  Based on the conservatism used in
the analyses, actual dietary exposure will be less than that presented
here.  FMC concludes that based on adequate % aPAD for all population
subgroups there is reasonable certainty that no harm will result from
the proposed additional uses of bifenthrin.

b. Chronic Exposure.  The reference dose (RfD) has been established at
0.013 mg/kg/day.  This RfD is based on a one-year oral study in dogs
with a LOAEL of 2.7 mg /kg/day and a NOAEL of 1.3  mg /kg/day, UF = 100
based on observations of increased incidence of tremors in both sexes. 
The Tier I chronic exposures for the general U.S. Population are
estimated to be 0.0047 mg/kg/day and utilize 34.9% of the cPAD.  The
chronic exposures for all infants <1 year old (most highly exposed
population subgroup) is estimated to be 0.0118 mg/kg/day and utilizes
90.6% of the cPAD.  Chronic dietary exposure estimates for children 1-2
years old is estimated to be 0.0096 mg/kg/day and utilizes 73.3% of the
cPAD.  Therefore, FMC concludes with reasonable certainty that no harm
will result from the proposed additional uses of bifenthrin.

		ii. Drinking water. 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 surface water.  A
comparison of the calculated Drinking Water Level of Concern (DWLOC)
value to the Estimated Environmental Concentration (EEC) is made.  If
the DWLOC exceeds the EEC value then there is reasonable certainty that
no harm will result from the short- or intermediate-term aggregate
exposure.  In the case of bifenthrin, monitoring data do not exist, so
the FIRST model was used to estimate a surface water residue and SCIGROW
for the groundwater.  Based on the analyses the acute aggregate
exposures to bifenthrin residues, the   DWLOC for all seasons for the
general US population was 11 ppm (11,000 ppb) while the modeled EEC, was
0.1 and 0.006 ppb for surface water and ground water respectively.  For
children (1-6 year old), the DWLOCs was 2.3 ppm (2300 ppb) while the
modeled EEC was the same as that for the whole US population.  For the
chronic aggregate exposures to bifenthrin residues, the   DWLOC for all
seasons for the US population was 291 ppb while the modeled EEC, was 0.1
and 0.006 ppb for surface water and ground water respectively.  For
children (1-6 year old), the DWLOCs was 26 ppb while the modeled EEC was
the same as that for the whole US population.  Since, the calculated
DWLOC values for all population subgroups exceeded the modeled EEC for
surface water and ground water residues, there is reasonable certainty
that no harm will result from aggregate exposures to bifenthrin
residues.

		2. Non-dietary exposure. The aggregate residential exposure analyses
were based on conservative screening-level assumptions.  The residential
risk assessments resulted in acceptable MOEs and a clear indication of
reasonable certainty of no harm.  The short-term analyses, all of the
route- and product-specific MOEs were greater than 100 and the aggregate
MOEs were greater than 100 for all population subgroups.  Based on the
above information, FMC concludes that bifenthrin does not pose a risk
due to short- and intermediate-term aggregate exposure.

D. Cumulative Effects

		To our knowledge there are currently no available data or other
reliable information indicating that any toxic effects produced by
bifenthrin would be cumulative with those of other chemical compounds;
thus only the potential risks of bifenthrin have been considered in this
assessment of its aggregate exposure.

E. Safety Determination

		1. U.S. population. Using the conservative Tier 1 exposure assessment
analyses the estimated chronic exposure to the U.S. Population is 0.0047
mg/kg/day and utilizes 35.9% of the cPAD.  In addition, the chronic
exposure estimates for all population subgroups (including infants and
children) are well below the cPAD of 0.013 mg/kg/day.  The acute dietary
exposure analyses at the 95th percentile for the general U.S. Population
is 0.0127 and utilizes 3.88% of the aPAD.  In addition, the acute
exposure estimates for population subgroups of concern (infants and
children) indicate that the maximum %aPAD or %cPAD utilized is 7.80%
(aPAD) and 90.6% (cPAD) .  Based on this information FMC concludes that
there is reasonable certainty that no harm will result from acute and
chronic exposure to bifenthrin.

		2. Infants and children. i. General.  In assessing the potential for
additional sensitivity of infants and children to residues of
bifenthrin, FMC considered data from developmental toxicity studies in
the rat and rabbit, a developmental neurotoxicity study, and a
two-generation reproduction study in the rat.  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 systemic toxicity. 
FFDCA Section 408 provides that the EPA may apply an additional margin
of safety for infants and children in the case of threshold effects to
account for prenatal and postnatal toxicity and completeness of the
database.  ii.  Developmental toxicity studies.  In the rabbit
developmental study, there were no developmental effects observed in the
fetuses exposed to bifenthrin.  The maternal NOAEL was 2.67 mg/kg/day
based on head and forelimb twitching at the LOAEL of 4 mg/kg/day.  In
the rat developmental study, the maternal NOAEL was 7.4 mg/kg/day, based
on treatment-related clinical signs and reductions in body weights,
adjusted maternal body weights, and corresponding reductions in food
consumption noted among dams receiving the LOAEL of 16.3 mg/kg/day.  The
developmental NOAEL was greater than 16.3 mg/kg/day based on lack of any
adverse fetal effects at levels up to and including 16.3 mg/kg/day. 
iii.  Developmental neurotoxicity study.  In a rat developmental
neurotoxicity study, pups were not more sensitive than the dams.  The
NOAEL for maternal toxicity was 50 ppm, based on tremors at the LOEL of
100 ppm.  The NOAEL for developmental neurotoxicity was also 50 ppm. 
iv.  Reproductive toxicity study.  In the rat reproduction study,
parental toxicity occurred as decreased body weight at 5.0 mg/kg/day
with a NOAEL of 3.0 mg/kg/day.  There were no developmental (pup) or
reproductive effects up to 5.0 mg/kg/day (highest dose tested).  v.
Conclusion.  Based on the absence of fetal effects and pup toxicity in
any of the referenced studies, 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 previously stated, aggregate exposure assessments utilized
no more than 45.5% of the aPAD or cPAD for either the entire U.S.
Population or any of the 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 bifenthrin residues.

F. International Tolerances

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 China 5.0 ppm, India 5.0 ppm, Taiwan 2.0 ppm, European Union 5.0 ppm.