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EPA REGISTRATION DIVISION CO MPANY NOTICE OF FILING FOR

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: [Richard Gebkin, (703) 305-6701]

INSTRUCTIONS: Please utilize this outline in p reparing the pesticide petition. In

cases where the outline element does not apply, please insert “NA-Remove” and

maintain the outline. Please do not chan ge the margins, font, or format in your pesticide petition. Simply replace the instructions that appear in green , i.e., “ [insert company name] ,” with the information specific to your action.

TEMPLATE:

Gowan Company

[Insert petition number]

EPA has received a pesticide petition (PP 6F8442) 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-dimethylet hyl) phenyl] ethoxy] quinazoline] in or on the raw agricultural commodity for hops at 30 ppm . EPA has determined that the petition contains data or information regarding the elemen ts 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 s upports 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. Virt ually 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

2. Analytical method. The basic analytical method was previously reviewed 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 a cetonitrile. An aliquot is transferred to a separatory funnel and partitioned between water and methylene chloride. A 10% portion of the methylene chloride laye r is evaporated and the residue is

reconstituted in acetonitrile for instrumental analysis by LC/MS/MS with positiveion electrospray ionization tandem mass spectrometry. The method had a Limit of Quantitation of 0.01 ppm and a Li mit of Detection of 0.003 ppm.

3. Magnitude of residues. The Agency previously reviewed 2008 residue data in hops and concluded the following:

Three field trials were conducted in U.S. EPA Regions 11 (WA and ID) and 12 (OR, near the border of Region 11) during the 2008 growing season. The use pattern of the field trial adequately reflects th e use pattern proposed for hops.

In 2014, a further four (4) trials were conduc ted on hops. A single foliar application of GWN-1708 (MAGISTER SC) was applied at the maximum labeled use rate of 0.45 lb. ai/acre (0.50 kg ai/ha) at seven d ays before harvest. The trials were conducted in U.S. EPA Regions 11 (2 trials in WA) and 12 (2 trials in OR). The two

trials conducted in WA were decline trials with sample s collected at 0, 7, 14, and 21 days after application.

At the PHI of 7 days, fenazaquin residues ranged from 8.71 ppm to 12.0 ppm, with a mean residue of 10.3 ppm. Results from th e decline trial (WA) showed that mean residues of fenazaquin declined from a high of 31.8 ppm at 0 DAA (days after application) to 4.74 ppm at 21 DAA, resulting in a half-life of 7.8 days. Results from

the 2 nd WA decline trial showed that mean residues of fenazaqui n declined from a high of 21.8 ppm at 0 DAA to 2.24 ppm at 21 DAA, resulting in a half-life of 6.4 days.

B. Toxicological Profile

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

and skin irritation.

2. Genotoxicity. A number of mutagenicity studies were conducted. The genotoxic database is complete. All test results for genotoxicity with fenazaquin have been negative.3

3. Reproductive and developmental toxicity. In rat and rabbit developmental toxicity studies, no evidence of increase d 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 effi ciency. 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 toxi city findings. Effects on body weight and weight gain and food intake efficiency were identified in parental animals of the rat developmental and reproduction studies an d 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 Can cer Assessment Review Committee reviewed the carcinogenicity study in hamsters, as well as the carcinogenicity study conducted in rats, the mutagenicity studies, and di scussed the possible carcinogenic mode of action of fenazaquin. Based on the weig ht of evidence of these studies, and in

accordance with the 2005 Guidelines for Ca rcinogen Risk Assessment, the members concluded that the negative hamster findi ngs 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 excrete d in the feces. Excretion of the dose was rapid with no accumulation or appa rent target organ. The metabolites found were the result of oxidation or hydrol ysis. 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 endo crine 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 complete d by the Agency (Federal Register, May 6, 2015, pages 25952-25958).4

i. Food. Acute Exposure. The acute dietary exposure risk estimate utilizes 3.05% (0.004581 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 ut ilized 8.26% (0.012396 mg/kg/day) of the aPAD at th e 95th percentile of exposure. Chronic Exposure. The proposed tolerances for fenazaquin in hops will not add to dietary risk. Chronic dietary exposures to registered and proposed crops range from 0.001115 mg/kg/day (2.2% of cPAD) for adults 20 – 49 years to 0.004253 (8.5% of cPAD) for children aged 1-2 years ol d, the most highly-exposed population subgroup. Chronic dietary exposure for th e U.S. population is estimated to be 0.001262 mg/kg/d (2.5% of cPAD). Thus, ch ronic dietary exposure to fenazaquin for all population subgroups is not of concern.

ii. Drinking water. The Agency has previously used screening level surface water exposure models in dietary exposu re analysis and risk assessment for fenazaquin in drinking water. Based on the Pesticide Root Zo ne Model /Exposure Analysis Modeling System (PRZM/EXAM S), 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 assessed residential exposure.

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

D. Cumulative Effects

EPA 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. Acute risk. Total acute dietary exposure to the US population from the proposed food uses is 0.015978 mg/kg/day, representing 10.65%

of the acute reference dose at 99.9 th percentile.

Short-and intermediate term risk. Short-term aggregate exposure takes into account short-term residential exposure plus chroni c exposure to food and water (considered to be a background exposure level). Fenazaqu in is currently regis tered for uses that could result in short-term residential expo sure, and the Agency has determined that it is appropriate to aggregate chronic expo sure through food and water with shortterm residential exposures to fenazaquin.5

Chronic risk. The total chronic exposure to the US population was 0.001262 mg/kg/day, representing 2.5% of the chronic reference dose.

2. Infants and children

. EPA previously has determined that reliable data show the safety of infants and children wo uld be adequately protected if the FQPA SF were reduced to 1X. The highest risk s calculated for any pre-teen dietary subgroup were 18.93% of the acute reference dose for children 1-2 years old and

8.5% of the chronic reference dose for the same subpopulation.

F. International Tolerances

The Codex has not established a MRL for fenazaquin.