 

COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE  (7/1/2006)

EPA Registration Division contact: Dan Peacock  (703) 305-5407

 

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TEMPLATE:

Gowan Company

[Insert petition number]

	EPA has received a pesticide petition ([insert petition number]) from
Gowan Company, 370 S. Main Street, Yuma, AZ   85364, 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.

(Options (pick one)

	1. by establishing a tolerance for residues of

	fenazaquin [3-[2-[4-(1,1-dimethylethyl) phenyl] ethoxy] quinazoline] in
or on the raw agricultural commodity pome fruit group at 0.35, cucurbit
group at 0.25, almond hulls at 4.5, apple wet pomace at 0.6, berry fruit
group at 0.6, fruiting vegetable group at 0.25, grape at 0.9, hop at
2.0, mint at 6.0, stone fruit group at 1.5, strawberry at 1.5, tree nut
group at 0.02, alfalfa forage at 4.5, alfalfa hay at 8.0 ppm,  avocado
at 0.15, citrus fruit group at 0.3, citrus oil at 2.5, cottonseed
(undelinted) at 0.5, cotton gin byproducts at 12.0, shelled dry bean
subgroup at 0.2, edible podded bean subgroup at 0.3, succulent beans and
pea subgroup at 0.02, field corn grain at 0.15, field corn forage at
9.0, field corn stover at 30, field corn aspirated grain fractions at
9.0, field corn refined oil at 0.6, sweet corn at 0.04 and sweet corn
forage at 9.0  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 FDDCA; 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. Apple metabolism work (MRID 45029914) demonstrates
that TRR are reduced to less than 25% of their original value at 70 DAT
after a late season treatment and are reduced to between 1 – 4% of
their original value at 105 DAT after an early season application. 
Virtually all of the TRR at 0 DAT is solvent washable fenazaquin on the
surface of the apples.  At 70 DAT identified parent fenazaquin is less
than 35% TRR.  At 105 DAT, 12 – 21% TRR was identified as parent
fenazaquin.  At harvest, fenazaquin is the predominant residue in apples
with smaller amounts of other metabolites.

	2. Analytical method. [Residues of fenazaquin are extracted from the
sample matrices by blending with acetonitrile.  An aliquot is
transferred to a separatory funnel and partitioned between water and
methylene chloride.  A 10% portion of the methylene chloride layer is
evaporated and the residue is reconstituted in acetonitrile for
instrumental analysis by LC/MS/MS with positive-ion electrospray
ionization tandem mass spectrometry.  The method had a Limit of
Quantitation of 0.01 ppm and a Limit of Detection of 0.003 ppm.]

	3. Magnitude of residues. [Residues of fenazaquin ranged from 0.023 to
0.082 mg/kg (ppm) in avocados, 0.031 to 1.65 ppm in alfalfa forage, 3.5
to 7.1 in alfalfa hay, 0.10 to 0.42 ppm in berries, 0.02 to 0.23 ppm in
whole citrus fruit, 0.013 to 0.325 ppm in undelinted cottonseed, 0.485
to 9.983 ppm in cotton gin trash, 0.02 to 0.17 ppm in cucurbit crops,
not detected to 0.168 ppm in dry beans, <0.01 to 0.223 ppm in fruiting
vegetables, 0.40 to 1.27 ppm in hops, not detectable to 0.28 ppm in pome
fruit, 0.12 to 1.20 ppm in stone fruit, 0.06 to 1.17 ppm in
strawberries, non-detected to 0.016 ppm in succulent beans and peas,
0.04 to 0.18 ppm in edible podded beans, 0.05 to 0.33 ppm in grapes,
0.359 to 1.27 ppm in hops, 0.52 to 5.45 ppm in mint, not detected to
0.051 ppm in field corn grain, not detected in sweet corn kernels plus
cob with husks removed, 0.254 to 6.04 ppm in corn forage, 0.101 to 21.3
ppm in corn stover, not detected to 0.02 ppm in tree nuts (0.22 to 1.17
ppm in almond hulls).]

B. Toxicological Profile

	1. Acute toxicity.  [EPA has reviewed the acute toxicity database and
has determined that fenazaquin is belongs in Category II for oral
toxicity; Category III for both inhalation exposure and eye irritation;
and Category IV for dermal exposure and skin irritation.  

	2. Genotoxicty. [The genotoxicological database is complete.  All test
results for genotoxicity with fenazaquin have been negative.]

	3. Reproductive and developmental toxicity. [In rat and rabbit
developmental toxicity studies, no evidence of increased quantitative or
qualitative susceptibility exists following in utero exposure to
fenazaquin.  There are no qualitative or quantitative pre-natal
susceptibility issues and no residual uncertainties in the rat
two-generation reproduction study.]

	4. Subchronic toxicity. [The major findings following repeated oral
administration in rats, hamsters and dogs were decreases in body weight,
body weight gain, food intake, and food efficiency.  The lowest NOAEL
observed during these studies was 5 mg/kg/day in a 90-day feeding study
in dogs.]

	5. Chronic toxicity. [At the doses used in chronic toxicity studies (up
to 35 mg/kg/day), there were no organ specific toxicity findings. 
Effects on body weight and weight gain and food intake efficiency were
identified in parental animals of the rat developmental and reproduction
studies and in the offspring of the reproduction rat study.  There were
no developmental findings in the rat study (up to 40 mg/kg) and no
parental or developmental findings of any kind up to 60 mg/kg/day in the
rabbit developmental study.

The EPA Health Effects Division Cancer Assessment Review Committee
reviewed the carcinogenicity study in hamsters, as well as the
carcinogenicity study conducted in rats, the mutagenicity studies, and
discussed the possible carcinogenic mode of action of fenazaquin.  Based
on the weight of evidence of these studies, and in accordance with the
2005 Guidelines for Carcinogen Risk Assessment, the members concluded
that the negative hamster findings along with the negative tumor
findings in the 24-month rat study and negative mutagenicity findings
support a cancer classification of “Not likely to Be Carcinogenic to
Humans” for fenazaquin.]

	6. Animal metabolism. [In rat, goat and hen metabolism studies,
orally-administered fenazaquin was quickly excreted in the feces. 
Excretion of the dose was rapid with no accumulation or apparent target
organ.  The metabolites found were the result of oxidation or
hydrolysis.  A new hen study demonstrates metabolism similar to rats and
goats.  No toxic metabolites were detected in any metabolism studies.]

	7. Metabolite toxicology. [No toxic metabolites of fenazaquin have been
identified in any metabolism study.]

	8. Endocrine disruption. [EPA has reserved endocrine testing
requirements for fenazaquin pending consideration of appropriate
screening and/or testing protocols being considered under the Agency’s
Endocrine Disruptor Screening Program.]

C. Aggregate Exposure

	1. Dietary exposure. [Sufficient residue data for fenazaquin are
available to assess the proposed tolerances and conduct a dietary risk
assessment.  The acute dietary risk assessment is based on the aPAD set
by the Agency at 0.1 mg/kg/day.  The chronic dietary risk assessment was
based on the cPAD of 0.05 mg/kg/day.  The risk assessments were modeled
with DEEM-FCID v. 2.16.  The maximum dietary risk for any dietary
subpopulation was a maximum of 20.19% of the aPAD and 17.2% cPAD.]

	i. Food. [A probabilistic risk analysis using field residue data with
an assumption of 100% crop treated was run.  Empirically-derived
concentration factors were used when such data were available.  Where no
such data were available, default values were used for processed
commodities.]

	ii. Drinking Food. [Tier I estimates for fenazaquin levels in untreated
drinking water generated by EPA in the non-food petition decision were
included in the dietary risk assessment.  The Agency estimates were
0.002632 and 0.000064 ppm for acute and chronic scenarios,
respectively.]

	2. Non-dietary exposure. [No homeowner uses are proposed for fenazaquin
at this time.]

D. Cumulative Effects

	[Fenazaquin does not share a mechanism of toxicity with another
registered pesticide nor does it share a common toxic metabolite with
any other registered pesticide.  There are no available data to indicate
that fenazaquin has a common mechanism of toxicity with other
substances.]

E. Safety Determination

	1. U.S. population. [Total acute dietary exposure to the US population
from all proposed food uses is 0.008681 mg/kg/day, representing 8.68% of
the acute reference dose.  The total chronic exposure to the US
population was 0.002964 mg/kg/day, representing 5.9% of the chronic
reference dose.]

	2. Infants and children. [The Agency has set the FQPA factor for
fenazaquin at 1X based on lack of neurotoxic and teratogenic effects. 
The highest risks calculated for any pre-teen dietary subgroup were
20.19% of the acute reference dose for children 1-2 years old and 17.2%
of the chronic reference dose for the same subpopulation.]

F. International Tolerances

	[No Codex MRL levels have been established for fenazaquin.  A number of
MRLs have been established for fenazaquin in crops in many other
countries.  EPA has established import tolerances for fenazaquin in
apples, pears, citrus fruit (except grapefruit) and citrus oil.]

