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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, PM 10, (703) 305-6701] INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In cases where the outlineelement does not apply, please insert"NA-Remove" and maintain the outline. Please do not changethe margins, font, or format inyour pesticide petition. Simply replace the instructions that appear in green, i.e., "[insert company name]," with the information specific toyour action. TEMPLATE: Gowan Company [Insert petition number] EPAhasreceived apesticidepetition ([insert petition number]) from Gowan Company, LLC,P.O. Box 556 Yuma,AZ 85366proposing,pursuant to section 408(d) ofthe Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFRpart 180. (Options (pick one) 1.byestablishing a tolerance forresidues of Hexythiazox, (trans-5-(4-chlorophenyl)-N-cyclohexyl-4-methyl-2- oxothiazolidine-3-carboxamide) inor onthe raw agricultural commodity bermudagrass, forageat 40ppm and bermudagrass, hay at 70 ppm. EPAhas determined that thepetition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA;however, EPAhas not fully evaluated the sufficiency ofthe submitted data atthis time or whetherthe data supports granting ofthepetition. Additional data maybe neededbefore EPA rules on thepetition. !.•••• A.Residue Chemistry *•••• • • 1.Plantmetabolism. The nature ofthe residues inplants is adequately •***/ ****** understood for purposes ofthis tolerance petition. Metabolism studies in fruit crops, ** , radish, tea and corn have been completed. The Agency has determined that the *.•*•* residues ofconcern are hex\'thiazox and itsmetabolites containing the • (4-chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moietj' calculated as the stoichiometric equivalent ofhexjThiazox. * ,,,2.Analytical method.The basic analytical method was previously reviewed by

the Agency in association with the establishment ofthe current tolerances with registrations of multiple commodities.The methods used in a new bermudagrass raw agricultural commodities study aredescribed fully in the study report which is submitted concurrently with this petition. 3.Magnitude ofresidues. A New Magnitude ofthe Residue data have been generated in bermudagrass in regions 9 and 10 to support regional registration. Four bermudagrass trials were conducted in EPA Regions 9 (one trial, AZ) and 10 (three trials, CA) in 2013 and 2014. These field trials will support regional registration (Regions 9 and 10) for hexythiazox in bermudagrass. The results from these trials show that after one application of Onager® IE Miticide at 0.1875 lb ai/A (0.210kg ai/ha) ± 5% residues of hexythiazox ranged from 6.58 to 23.5ppm (mean = 13.2 ppm ± 6.58) on eight bermudagrass forage RAC samples collected 0 DAA. Hexxthiazox residues ranged from 13.4 to 30.6 ppm (mean = 21.5 ppm ± 7.22) on eight bermudagrass hay RAC samples collected 7DAA. B. ToxicologicalProfile 1. Acutetoxicity. A battery ofacute toxicitv" studies places technicalgrade hexythiazox in Toxicity' Category IV foracute oral toxicity (LDso >5,000 mg/kg), Category IIIfor acute dermaltoxicity (LDso >5,000 mg/kg). Category HI foracute inhalation toxicity' (LCso >2.0 mg/L), Category' III for primary eye irritation (showed mild irritation (reddened conjunctiva) and Category IV for dermal irritation (non irritant). Hexythiazox is a non-sensitizer. 2. Genotoxicity.A number of mutagenicity studies wereconducted. Theseare a mammalian erythrocyte micronucleus test [MRID 45480101], a mammalian cell forward gene mutation assay [MRID 00155154], a rat primary hepatocy te unscheduled DNA synthesis assay [MRID 00156893], a clastogenic evaluation in an in vitro cytogenetic assay measuring chromosomal aberration in Chinese hamster ovary cells [MRID 00156894], and an Ames study withSalmonella [MRID 44955710]. All these mutagenicity- tests were negative. 3. Reproductive anddevelopmental toxicity.In a developmental toxicity study with rats [MRID 00147578], thefetotoxicity NOEL yyas 240 mg/kg/day, and the compound yvas not embryotoxic at the highest dose tested, 2160 mg/kg/day. In a developmental toxicit)' study with rabbits [MRID 00146555], no developmental toxicity yvas observed at the highest dose tested, 1080 mg/kg/day. In a twogeneration reproduction study with rats [MRID 00147578 and 00151360], no •••*, reproductive effects yvere observed at 2400ppm in the diet (>illO and >139 mg/kg/day, males and females, respectively). It is concluded that the NOEL for developmental and reproductive effects is greater than 10 times the chronic NOEL. ••••

»••• •• •• •. •••••, • • • • • ••••• 4. Subchronic toxicity.In a 1-month feeding study in dogs, the NOAEL was 1.75 mg/kg/day and the LOAEL yvas 12.5 mg/kg/day, b ased on increased liver and adrenal weights. !•••• • •••5. Chronic toxicity. In a 1-year feeding studyin dogs, the NOAEL was2.5

mg/kg/day and the LOAEL was 12.5mg/kg/day, based on increased alkaline phosphatase, increased adrenal and liver weights, and liver and adrenal lesions. In acarcinogenicity study in mice, the NOAEL was 36 mg/kg/day and the LOAELwas 215 mg/kg/day. Effects were decreased bodyweight in males and increased hepatocellular carcinomas and combined adenoma/carcinomas. In a chronic feeding/carcinogenicitj'study in rats, the NOAEL (systemic) was26 mg/kg/day and the LOAEL (systemic) was 180 mg/kg/day based on decreased body weight gain and increased liver weights in both sexes. A 2009report from the Cancer Assessment Review Committee (CARC) (September 02,2009, PC Code 128849, TXR 0055255) noted that the NOAEL of2.5 mg/kg/day, from the one year toxicity study in dogs, used in establishing the chronic reference dose (RfD) is approximately 65-fold lower than the lowest dose (163 mg/kg/day) that induced tumors. Thus, thechronic RfD of0.025 mg/kg/day would beprotective of all chronic effects including potential carcinogenicity ofhexA'thiazox. The CARC concluded that the evidence as a wholewas not strong enough to warrant the use of a linear low dose extrapolation model applied to the animal data (Ql*) for a quantitative estimation ofhuman risk, as had been previously assessed in October 16,1998, [63.FR55540]. 6. Animal metabolism. The metabolism of hexvthiazox has been studied in goats, hens and rats. Metabolic pathways in the animal aresimilar to those in plants.7. Metabolite toxicology. Thereare no metabolites oftoxicological concern based on a differential metabolism between plants and animals. 8. Endocrine disruption. Information concerning possible endocrine effects of hexythiazox similar to effects produced by a naturally occurring estrogen,or other endocrine effects is available from the two-generation rat reproduction study, the rat and rabbit developmental studies and the rat and dog chronic studies.There is no evidence from these studies that hexjthiazox induces estrogenic or other endocrine effects. , ,

C.Aggregate Exposure *'*' •*** •
• • • 1. Dietary exposure. Dietaiy Exposure from food. A dietary risk assessment -,. •• •• for all registered crops has been completed by the Agency (Federal Register, July

. ••;**< 17, 2013, pages 42693-42699). i.Food. Acute Exposure. No acuteendpoint has been identified in the toxicological studies for hexythiazox; therefore, a quantitative acute dietarj' • exposure assessment isunnecessary. •* *ChronicExposure. The proposed regional tolerances for hexjthiazox in

bermudagrass will not add to dietarj' risk. A recent tier 1chronic assessment shows employing tolerance residue values, theassumption of 100% crop treated and default processing factors shows that the maximally exposed subpopulation (children 1-2 years old) utilized 93.4% ofthe cPAD. ii.Drinking water. The Agency has previously used screening level surface water exposure models in dietary exposure analysis and risk assessment for hexythiazox in drinking water. Based on the PesticideRoot Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS), the estimated drinkingwater concentration (EDWC) ofhexj'thiazox for chronic assessment was estimated to be 4.31parts per billion (ppb). (Federal Register, July 17, 2013, pages 42693-42699) 2. Xon-dietary exposure. EPA has previously determined that potential residential exposures to hexjthiazox are below levels of concern. D. CumulativeEffects EPA has not found that hexjThiazox shares a common mechanism oftoxicity with any other substances. E. SafetyDetermination 1. U.S.population. Acute risk. No adverse effect resulting from a single oral exposure to hexythiazox has been identified, thus hexjthiazox is not expected to pose an acute risk. Short-and intermediate term risk. EPA has previously concluded that there are no short term or intermediate term risks ofconcern from exposure to hexythiazox. Chronic risk. The proposed regional tolerances for hexythiazox in bermudagrass will not add to dietaiy risk. Chronic residential exposure to the residues of hexj'thiazox is not expected. 2. Infants andchildren. EPA previously has determined that reliable data show the safety' ofinfants and children would be adequately protected if the FQPA SFwere reduced to IX. Based on these risk assessments, it can be concluded that there is a reasonable certainty that no harm will result to the general population, or to infants and children from aggregate exposure to hexythiazox residues. •••*. * •••* F.International Tolerances There are no international maximum residue levels established for hex>ihiazox on bermudagrass. •••• ••
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