EPAREGISTERED DIVISION COMPANY NOTICE OFFILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER. EPA Registration Division contact: Mark Suarez, PM 13, (703) 305-0120

INSTRUCTIONS: Please utilize this outline in preparingtolerance petition documents. In cases wherethe outline element does not apply please insert "NARemove" and maintain the outline. The comment notes that appearon the left margin represent hidden typesetting codes designed to expedite the processing ofthe FederalRegister document. Please do notremove or alterthese comment notes or change the margins, font, orformat in yourdocument. Simply replace the instructions that appearin italics and brackets, i.e., "[insertcompanyname]," with the information specific to your action.] [Gowan Company] [Insert petition number] EPA 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) oftheFederal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFRpart 180. (Options (pick one) 1. by amending the regional restriction ofa tolerance to include Arizona for residues of Hexythiazox (trans-5-( 4-chlorophenyll)-N-cyclohexyl-4-methyl-2- oxothiazolidine-3-carboxamide) in or on the raw agricultural commodity cotton, gin byproduct at 3 parts per million (ppm) and cotton, undelinted seed at0.2 parts per million (ppm). EPA has determined thatthe petition contains data or information regarding the elements set forth in section408 (d)(2) ofthe FDDCA; however, EPA has not fully evaluated the sufficiency ofthe submitted data atthis time or whether the data supports granting ofthe petition. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry
I.Plant metabolism

. The nature ofthe residues in plants is adequately understood for purposes ofthis tolerance. Metabolism studies in fruit crops, radish, tea and corn have been completed. TheAgency has determined thatthe residues of concern arehexythiazox and its metabolites containingthe (4-chlorophenyl)-4-

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methyl-2-oxo-3-thiazolidine moiety. 2. Analytical method. A practical analytical method, high pressure liquid chromatography with a UV detector, which detects and measures residues of hexythiazox and its metabolites as a common moiety, is available for enforcement purposes with a limit ofdetection that allows monitoring offood with residues at or above the levels set in this tolerance. 3. Magnitude of residues

. Data on file with EPA supports the amendment to the cotton tolerance. B. Toxicological Profile 1. Acute toxicity

. A battery ofacute toxicity studies places technical grade hexythiazox in Toxicity Category IV for acute oral LD50 (LD50 > 5,000**mi~ligramlkilograms** (mglkg)), Category III for dermal LD50 (LD50 >5,000 mglkg), Category III for inhalation LC50 (LC50 >2.0 mg!L), Category III for primary eye irritation (showed mild irritation (reddened conjunctiva)), Category IV for dermal irritation (non irritant). Hexythiazox is a non-sensitizer. Acute toxicological studies place technical grade hexythiazox in Toxicology Category III. 2. Genotoxicty

. Thefollowing genotoxicity studies were all negative: Ames gene mutation, CHO gene mutation, CHO chromosome aberration, mouse micronucleus and rat hepatocyte unscheduled DNA synthesis. 3. Reproductive anddevelopmental toxicity

. In a developmental toxicity study in rats, the maternalNo-Adverse-Effect-Level (NOAEL) was 240 mglkg/day and the maternal Lowest-Adverse-Effect-Level (LOAEL) was 720 mglkg/day based on increased ovarianweights and decreased bone ossification. In a developmental toxicity study in rabbits, the maternal NOAEL was 1,080 mglkg/day {HDT); the maternalLOAEL was not determined. The developmental NOAEL was 1,080 mglkglday (HDT); the developmental LOAELwas not determined. In a 2- generation reproduction study in rats, the parentalNOAEL was 35 mglkglday and the parental LOAELwas 200 mglkglday based on decreased body weight gain, decreased food consumption and efficiency, and increased liver, kidney and ovarian weights. The reproductive NOAEL was 35 mglkg/day and the reproductive LOAEL was 200 mglkg/day based on decreased pup bwt duringlactation, delayed hair growth and eye opening. 4. Subchronic toxicity

. In a 1-monthfeeding study in dogs, the NOAEL was 1.75 mglkg/day and the LOAELwas 12.5 mglkg/day, based on increased liver and adrenalweights. 5. Chronic toxicity. In a 1-yearfeeding study in dogs, the NOAEL was 2.5 mglkg/day and the LOAELwas 12.5 mglkglday, based on increased alkaline phosphatase, increased adrenal and liverweights, and liver and adrenal lesions. In a carcinogenicity study in mice, the NOAEL was 36 mglkg/day and the LOAELwas 215 mglkglday. Effects were decreased bodyweight in males and increased

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hepatocellular carcinomas and combined adenoma/carcinomas. In a chronic feeding/carcinogenicity study in rats, the NOAEL (systemic) was 26 mglkglday and the LOAEL (systemic) was 180 mglkg/day based on decreased body weight gain and increased liverweights in both sexes. A 2009 report from the CancerAssessment Review Committee (CARC) (September 02, 2009, PC Code 128849, TXR0055255) noted that the NOAEL of2.5 mg/kglday, from the oneyeartoxicity study in dogs, used in establishing the chronic reference dose (RID) is approximately 65-fold lowerthan the lowest dose (163 mg/kglday) that induced tumors. Thus, the chronic RID of0.025 mg/kg/day would be protective of all chronic effects including potential carcinogenicity ofhexythiazox. The CARC concluded thatthe evidence as a wholewas not strong enough to warrantthe use of a linearlow dose extrapolation model applied to the animal data (Q1*) for a quantitative estimation ofhuman risk, as had been previously assessed in October 16, 1998, [63.FR55540]. 6. Animal metabolism

. The metabolism ofhexythiazox has been studied in goats, hens and rats. Metabolic pathways in the animal are similarto those in plants.7. Metabolite toxicology. There are no metabolites oftoxicological concern based on a differential metabolism between plants and animals. 8. Endocrine disruption. No specific test have been conducted with hexythiazox to determine whetherthe chemical may have any effect in humans that is similarto an effect produced by a naturally ocurring estrogen or other endocrine effects. However, there were no significant findings in otherrelevanttoxicity tests, i.e., teratology and multi-generational reproduction studies,which would suggest that hexythiazox produces effects characteristic ofthe disruptions ofhormones. C. Aggregate Exposure 1. Dietary exposure. Dietary Exposure from food. A dietary risk assessment for all registered crops has been completed by theAgency (December 14, 2011, FR Doc No. 2011-32086) i. Food. Acute Exposure. No acute endpoint has been identified in the toxicological studies for hexythiazox; therefore, a quantitative acute dietary exposure assessmentis unnecessary. ChronicExposure. A tier 1 chronic risk assessment by Gowan Company indicates that registered uses as well as uses proposed in the meantime and still under evaluation result in a dietary risk ofnot more than 68.5% ofthe chronic Population Adjusted Dose (cPAD) for any population. ii. Drinking Water

. The Agency used screening level water exposure models in the dietary exposure analysis and risk assessment for hexythiazoxin drinkingwater.

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...**~'** Based on the Pesticide Root Zone Model/ExposureAnalysis Modeling System (PRZM/EXAMS) the estimated drinkingwater concentration (EDWC) of hexythiazox for chronic exposures for non-cancer and cancerassessments is estimated to be 4.5 parts perbillion (ppb) for surfacewater. Since surfacewater residue values greatly exceed groundwaterEDWCs, surfacewaterresidues were used in the dietary riskassessment. 2. Non-dietary exposure. HED has conducted a residential risk assessment to support approved uses on turf, ornamental landscape plantings, ornamental plants, orchids and residential fruit trees, nut trees and caneberries. The Agency concluded that therewere no residential risks ofconcern associated with these uses (January 28,2010 EPA Memo. PRCode: 128849, DP BarcodeD372889.) D. Cumulative Effects EPAhas not found thathexythiazox shares a common mechanism oftoxicity with any other substance. E. Safety Determination 1. USpopulation. Acute risk. No adverse effect resulting from a single oral exposure to hexythiazox has been identified, thus hexythiazox is not expected to pose an acute risk. Short-and intermediateterm risk. EPA has concluded the combined short-term food, water, and residential exposures result in aggregate MOEs of 14,000 for adults and 1,900 for children. Because EPA's level ofconcern for hexythiazox is a MOE of 100 orbelow, these MOEs are not ofconcern. Chronic risk. Chronic exposure to hexythiazox from food andwaterwill utilize no more than 68.5% ofthe cPAD for the population group receiving the greatest exposure (children 1-2 years old). This assessment utilized existing tolerance values, assumed 100% crop treated, and utilized default processing factors. Chronic residential exposure to residues ofhexythiazox is not expected. 2. Infants andchildren. Based on these risk assessments, it can be concluded thatthere is a reasonable certaintythatno harmwill result to the general population, orto infants and children from aggregate exposure to hexythiazox residues. F. International Tolerances TheEuropean Union, Iceland, Norway, Israel, Russia, and Switzerland have established an MRL of0.5 ppm for hexythiazox on cottonseed. Mexico and Honduras have established an MRL of0.2 ppm for hexythiazox on cottonseed. Taiwan has established an MRL of0.05 for hexythiazox on cottonseed. Turkey has established an MRL of0.02 for hexythiazox on cottonseed.