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E PA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

E PA Registration Division contact: [ Richard Gebkin, (703) 305-6701]
INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In cases where the outline element does not apply, please insert “NA -Remove” and maintain the outline. Please do not change the margins, font, or format in your pesticide petition. Simply re place the instructions that appear in green , i.e., “ [ insert company name] ,” with the information specific to your action.
TEMPLATE:

G owan Company [ Insert petition number ]

E PA has received a pesticide petition ([ insert petition number ]) from Gowan Company, LLC, P.O. Box 556 Yuma, AZ 85366 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 -d imethylethyl) phe nyl] e tho x y] qui nazoline] in or on the raw agricultural commodity f or Tre e Nut crop group 14-12 at 0.02 ppm

. EPA h as d etermined th at the p etition c ontains d ata or inf or mation r egarding th e e lements s et forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency o f th e s ubmitted d ata 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 i s 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

2. Analytical method. The basic analytical method was previously rev iewed by the Agency in association with the establishment of the current tolerances with registrations of multiple commodities. 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. M agnitude of residues. Residues of fenazaquin ranged from not detected to 0.02 ppm in tree nuts

. The Agency previously reviewed residue data and concluded the following:

T

rials were con ducted with the representative commodities pecan (5 trials) and almonds (5 trials). The pecan data yielded a tolerance estimate of 0.02 ppm, and the almond data yielded a tolerance estimate of 0.015 ppm. The higher value, 0.02 ppm, was used as the toleranc e for the tree nuts group.

T

rial samples (5) were also analyzed for almond hulls, and the tolerance estimate is 4 ppm.

B. Toxicological Profile
1. Acute toxicity. EPA has reviewed the acute toxicity database and has determine d that fenazaquin 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. Genotoxici ty. A number of mutagenicity studies were conducted

. The genotoxic 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 observe d 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 353

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.

T he 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
con cluded 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 metaboli sm. 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.

7. Metabolite toxicology

. No toxic metabolites were detected in any metabolism study.

8. Endocrine disruption

. There is no evidence of endocrine disruptor effects in the fenazaquin database.

C . Aggregate Exposure

1. Dietary exposure. Dietary Exposure from food. A dietary risk assessment for all registered crops has been completed by the Agency (Federal Register, May 6, 2015, pages 25952-25958 ).

i. Food. Acute Exposure

. The acute dietary exposure risk estimate utilizes 2.77% (0.004156 mg/kg/day) of the acute population- adjusted dose ( aPAD) for the U.S. population at the 95th percentile of exposure. The most highly- exposed population subgroup was children 1 to 2 years old which utilized 9.64% (0.014463 mg/kg/day) of the aPAD at the 95th percentile of exposure. Chronic Exposure

. The propo sed tolerances for fenazaquin in t ree nut crop group will not add to dietary risk. Chronic dietary exposures to registered and pr oposed crops range from 0.000658 mg/kg/day (1.3% of cPAD) for adults 20 – 49 years to 0.004253 (8.5% of cPAD ) for children aged 1

- 2 years old, the most highly

- exposed population subgroup. Chronic dietary exposure for the U.S. popula tion is estimated to be 0.000995 mg/kg/d (2.0% of cPAD). Thus, chronic dietary exposure to fenazaquin for all population subgroups is not of concern.4

ii. Drinking water

. The Agency has previously used screening level surface water exposure models in dietary exposure analysis and risk assessment for fenazaquin in drinking water. Based on the Pesticide Root Zone Model /Exposure Analysis Modeling System (PRZM/EXAMS), the estimated drinking water concentration (EDWC) of fenazaquin for acute and chronic exposures were estimated to be 5.74 parts per billion (ppb). ( Federal Register, May 6, 2015, pages 25952-25958).

2. Non-dietary exposure

. EPA has previously a ssessed residential exposure

. Since there is no residential incidental oral exposure expected for children 1<2 years old on ornamental plants, a post-application exposure assessment was not conducted. The inhalation exposure assessment performed for residential handlers is representative of worst

- case inhalation exposure and is considered protective for post-application inhalation scenarios.

D . Cumulative Effects

E PA has not found fenazaquin to share a common mechanism of toxicity with any other substances, and fenazaquin does not appear to produce a toxic metabolite produced by other substances.

E . Safety Determination

1. U.S. population. A cute risk

. T otal acute dietary exposure to the US population from the proposed food uses is 0.020052 mg/kg/day, representing 13.37% of the acute reference dose. Short

- and intermediate term risk

. Short -term aggregate exposure takes into account short

- term residential exposure plus chronic exposure to food and water (considered to be a background exposure level). Fenazaquin is currently registered for uses that could result in short

- term residential exposure, and the Agency has determined thatit is appropriate to aggregate chronic exposure through food and water with shortterm residential exposures to fenazaquin. Chronic risk

. The total chronic exposure to the US population was 0.000995 mg/kg/day, representin g 2.0% of the chronic reference dose.

2. Infants and children

. EPA previously has determined that reliable data show the safety of infants and children would be adequately protected if the FQPA SF were reduced to 1X. The highest risks calculated for any pre

- teen dietary subgroup were 23.03 % of the acute reference dose for children 1 -2 years old and 6.6 % o f the chronic reference dose for the same subpopulation.

F

. International Tolerances

T he Codex has not established a MRL for fenazaquin.