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EPA REGISTRATION DIVISION COMPANY 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 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 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-dimethylethyl) 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 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 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. 
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 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 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 positiveion 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. 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 the use pattern proposed for hops. 

In 2014, a further four (4) trials were conducted 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 days 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 samples 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 the 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 2nd WA decline trial showed that mean residues of fenazaquin 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 Category II for oral toxicity; 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. 
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 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. 

 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). 
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 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 utilized 8.26% (0.012396 

mg/kg/day) of the aPAD at the 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 old, the most highly-exposed population 

subgroup. Chronic dietary exposure for the U.S. population is estimated to be 

0.001262 mg/kg/d (2.5% of cPAD). Thus, chronic 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 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 assessed 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

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 99.9th percentile. 

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 that 

it is appropriate to aggregate chronic exposure through food and water with shortterm residential exposures to fenazaquin. 
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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 would be adequately protected if the FQPA 

SF were reduced to 1X. The highest risks 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.