Document ID: EPA-HQ-OPP-2011-0541-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2011-09-07T04:00Z

<EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE
PETITIONS 

<EPA Registration Division contact:  Sidney Jackson (703) 305-7610>

<Interregional Research Project Number 4 (IR-4) >

<Pesticide Petition Number: 1E7881>

<	EPA has received a pesticide petition (PP # 1E7881) from Interregional
Research Project Number 4 (IR-4), 500 College Road East,  Suite 201 W,
Princeton, NJ 08540 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 180.566 by establishing a tolerance for combined residues of the
insecticide fenpyroximate (E)-1,1-dimethylethyl
4-[[[[(1,3-dimethyl-  5-phenoxy-1H-pyrazol-4-yl)  methylene]
amino]oxy]methyl]  benzoate and its Z-isomer, (Z)-1,1-dimethylethyl
4-[[[[(1,3-dimethyl-5-
phenoxy-1H-  pyrazol-4-yl)methylene]  amino]oxy]  methyl]benzoate
in or on the raw agricultural commodities:  Avocado at 0.20 parts per
million (ppm), Sapote, black at 0.20 ppm, Canistel at 0.20 ppm, Sapote,
mamey at 0.20 ppm, Mango at 0.20 ppm, Papaya at 0.20 ppm, Sapodilla at
0.20 ppm, Star apple at 0.20 ppm, Bean, snap, succulent, at 0.40 ppm,
and Tea, plucked leaves at 15 ppm.  Revisions to the existing tolerances
are the following:  Cucumber at 0.25 ppm, Fruit, citrus, citrus, group
10-10 tolerance at 0.60 ppm, Vegetable, fruiting, group 8-10 tolerance
at 0.20 ppm, and Fruit, pome, group 11-10 tolerance at 0.40 ppm. EPA has
determined that the petition contains data or information regarding the
elements set forth in section 408 (d)(2) of  FDDCA; however, EPA has not
fully evaluated the sufficiency of the submitted data at this time or
whether the data support granting of the petition. Additional data may
be needed before EPA rules on the petition.  

>

<A. Residue Chemistry>

<	1. Plant metabolism. The metabolism of fenpyroximate and z-isomer has
been studied in cotton, apples, grapes, and citrus and is well
understood. The major residue in plants is fenpyroximate and z-isomer,
with very low levels of several degradates. Metabolism in plants
involves hydrolysis of the ester and methyleneamino ether links,
N-demethylation, oxidation, and conjugation of the polar metabolites.

	2. Analytical method. Based upon the metabolism of fenpyroximate in
plants and the toxicology of the parent and metabolites, quantification
of the parent, fenpyroximate and the z-isomer, combined as fenpyroximate
is sufficient to determine toxic residues in plants. As a result an
enforcement method has been developed which involves extraction of
fenpyroximate from crops with acetone, filtration, partitioning and
cleanup, and analysis by gas chromatography using a nitrogen/phosphorous
detector. The method has undergone independent laboratory validation as
required by PR Notice 88-5 and 96-1. 

>

<	3. Magnitude of residues. Magnitude of residues in crops-

Field residue trials meeting EPA study requirements have been conducted
at the maximum label rate for avocado, cucumbers, tea, and snap beans2. 
Results from these trials demonstrate that the highest fenpyroximate and
z-isomer residues found will not exceed the proposed tolerances when the
product is applied following the proposed use directions.  

<B. Toxicological Profile>

<

1.  An extensive battery of toxicology studies has been conducted with
fenpyroximate.  EPA has evaluated the available toxicity data and
considered their validity, completeness, and reliability as well as the
relationship of the results of the studies to human risk  The nature of
the toxic effects caused by fenpyroximate is discussed in Unit III.A. of
the Final Rule on Fenpyroximate Pesticide Tolerance published in the
Federal Register on April 10, 2001 (66 FR 18561) (FRL-6773-2).   An
assessment of toxic effects caused by fenpyroximate including the
toxicological endpoints of concern is also discussed in Unit III.A. and
Unit III B. of the Federal Register dated June 10, 2004   (FRL-7362-9)
(89 FR 32457).

<	2. Animal metabolism. The qualitative nature of the residues of
fenpyroximate and its z-isomer, in animals is adequately understood.
Fenpyroximate was not metabolized to volatiles to any significant
degree.  The majority of either benzyl or pyrazole labels (approximately
70 % to 92 %) is excreted in the feces. Urinary excretion accounts for
less (approximately 9 % to 18 %) of the label.  Thus, feces and urine
are the major routes of excretion for fenpyroximate.  Tissue did not
accumulate fenpyroximate or its metabolites to any great extent.  The
greatest levels of label were in liver, kidneys, adrenals, and fat (to a
lesser degree).  In blood, nearly all of the label is in the plasma.   

	3. Metabolite toxicology. No toxicologically significant metabolites
were detected in plant or animal metabolism studies for cotton, apples,
or or grapes.    

8. Endocrine disruption. Chronic, lifespan, and multigenerational
bioassays in mammals and acute and subchronic studies on aquatic
organisms and wildlife did not reveal any endocrine effects for
fenpyroximate.  Any endocrine related effects would have been detected
in this comprehensive series of required tests.  The probability of any
such effect due to agricultural uses of fenpyroximate is negligible.

>

<C. Aggregate Exposure>

<	1. Dietary exposure. Acute and chronic dietary risk analyses were
conducted to estimate to potential fenpyroximate residues in/on the
following crops: avocado, black sapote, canistel, mamey sapote, mango,
papaya, sapodilla, bell and non-bell peppers, cantaloupe and other
melons, cotton, cranberries, eggplant, grape, grape raisins, okra, snap
beans, cucumbers, strawberries, tomatoes, citrus fruits, hops, mint,
pome fruits, tree nuts, tea, and meat, milk, and honey using LifeLine™
version 4.3.  Residue estimates for water consumption were based on
PRZM3/EXAMs and SCIGROW models and exposure assessments using LifeLineTM
version 5.0.  

	i. Food. The acute dietary exposure was based on the following
assumptions: residues at tolerance levels, 100% crop treated, and
LifeLine™ version 5.0, default processing factors for all
registered/proposed commodities/processed fractions except for the
following noted fractions (Tier 1).  A processing factor of 0.11 was
used apple, grape, pear, and tomato for juice based on processing study
data and 0.06 x for orange juice. No processing factors were used for
oils since they were adequately represented by tolerance levels.  The
acute dietary aPAD (acute population adjusted dose) was set at 0.05
mg/kg/day for females aged 13-50 years old based on a developmental
toxicity study in rats that had an oral NOEL of 5 mg/kg/day.  The
chronic dietary exposure was based on the following assumptions: 
Residues at tolerance levels, 100% crop treated, and using USDA survey
data where available.  A processing factor of 0.11 was used for juice
based on processing study data. The chronic dietary cPAD (chronic
Population Adjusted Dose) was determined to be 0.01 mg/kg/day for the
general population, based on an oral NOAEL of 0.97 mg/kg/day in the
two-year rat chronic/oncogenicity study.  The resultant safety factor
used to establish the cPAD was 100.  There was not likely any evidence
of carcinogenicity. 

	ii. Drinking water. The residue of concern in drinking water was
determined to be fenpyroximate and its z-isomer.  There are no
established maximum contaminant levels or health advisory levels for
residues of fenpyroximate in drinking water.  In the absence of
comprehensive water monitoring data, the Agency uses the FQPA Index
Reservoir Screening Tool or the Pesticide Root ZoneModel/Exposure
Analysis Modeling System (PRZM/EXAMS) to produce estimates of pesticide
concentrations in an index resevoir.   The SCI-GROW model is used to
predict pesticide concentrations in shallow ground water. For a
screening-level assessment for surface water EPA will use FIRST (a tier
1 model) before using PRZM/EXAMS (a tier 2 model). The FIRST model is a
subset of the PRZM/EXAMS model that uses a specific high-end runoff
scenario for pesticides. Both FIRST and PRZM/EXAMS incorporate an index
reservoir environment, and both models include a percent crop area
factor as an adjustment to account for the maximum percent crop coverage
within a watershed or drainage basin.

None of these models include consideration of the impact processing
(mixing, dilution, or treatment) of raw water for distribution as
drinking water would likely have on the removal of pesticides from the
source water. The primary use of these models by the Agency at this
stage is to provide a screen for sorting out pesticides for which it is
unlikely that drinking water concentrations would exceed human health
levels of concern.

The estimated drinking water concentrations (EDWCs) in surface water
were determined using the Tier II PRZM (Pesticide Root Zone Model) and
EXAMS (Exposure Analysis Modeling System (PE4-PL, version 01).  PRZM is
used to simulate pesticide transport as a result of runoff and erosion
and spray drift from an agricultural field and EXAMS estimates
environmental fate and transport of pesticides in surface water.  The
EPA estimated that the EWDCs of fenpyroximate for acute exposures are
estimated to be 8.74 parts per billion (ppb) for surface water and 0.001
ppb for ground water.  For chronic exposures for non-cancer assessments
are estimated to be 0.51 ppb for surface water and 0.001 ppb for ground
water.    Modeled estimates of drinking water concentrations were
directly entered into the dietary exposure model.  For acute dietary
risk assessment, the water concentration value of 8.74 ppb was used
while for chronic dietary risk assessment, the water concentration of
0.51 ppb was used to assess the contribution to drinking water.  The
actual drinking water values would be much lower than the levels
predicted in the hypothetical, small, stagnant farm pond model since
drinking water derived from surface water would normally be treated
before consumption. Based on these analyses, the contribution of water
to the dietary risk estimate is negligible. Therefore, based on the
dietary and drinking water assessments, aggregate exposure to residues
of fenpyroximate and its z-isomer in food and water can be considered to
be negligible.

 >

<	2. Non-dietary exposure.  The term residential exposure is used in
this document to refer to non-occupational, non-dietary exposure (e.g.
for lawn and garden pest control, indoor pest control, termiticides, and
flea and tick control on pets). Fenpyroximate is not registered for use
on any sites that would result in residential exposure. 

>

<D. Cumulative Effects 

Fenpyroximate is a mitochondrial electron transport inhibitor acting at
Site I, which is similar to pyridaben, but quite different than other
established acaricides.  All relevant toxicological data has been
provided to the EPA.  A determination has not been made that
fenpyroximate has a common mechanism of toxicity with other substances. 
Fenpyroximate does not appear to produce a common toxic metabolite with
other substances. Therefore, for the purposes of this notice of filing,
there should be no consideration of cumulative risk that would require
assessment.  

>

<E. Safety Determination>

<	1. U.S. population.

 i. Acute risk.  Using the conservative assumptions discussed above,
based on the completeness and reliability of the toxicity data, it is
concluded that aggregate exposure to the proposed uses of fenpyroximate
will occupy at most 12. 1 % of the acute reference dose of females
(13-49).  

>

ii. Chronic Risk.  Based on the toxicology data base and available
information on anticipated residues, the chronic dietary exposure to the
U.S. Population (total) was estimated to be  24.5 % of the estimated
chronic population adjusted dose (cPAD).

<

2. Infants and children. Chronic exposure to food and water to children
from 1-2 years old, the highest exposed population subgroup, was 75.2 %
of the cPAD.  EPA has determined that reliable data support the
uncertainty factor (100 for intraspecies variability) for fenpyroximate.
 EPA deemed an additional FQPA safety factor is not necessary to be
protective of infants and children.  EPA generally has no concern for
exposures below 100% of the cPAD. The Agency has considered the
potential aggregate exposure from food, water and non-occupational
exposure routes and has concluded aggregate exposure is not expected to
exceed 100% of the chronic reference dose, and consequently, has
determined there is a reasonable certainty that no harm will occur to
infants and children from aggregate exposure to residues of
fenpyroximate.

 

>

<F. International Tolerances>

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⌀ in/on the proposed crops.  Therefore, harmonization is not an issue.
 

	 

>

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