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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 inpreparing 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 inyour pesticide petition. Simply replace the instructions that appear in green, i.e., "[insert company name]," with the information specificto your 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 FederalFood, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend40 CFRpart 180. (Options (pick one) 1.by establishing a tolerance forresidues of Hexjthiazox, (trans-5-(4-chlorophenyl)-N-cyclohex>l-4-methyl-2- oxothiazolidine-3-carboxamide) inor on citrus group 10,fruit at0.6 ppm, citrus, dried pulp at 0.6 ppm,and citrus, oil at26 ppm. EPAhas determined that thepetition contains data or informationregarding the elements set forth in section 408 (d)(2) of FDDCA;however, EPAhas not fully evaluated the sufficiency ofthe submitted data at this time or whetherthe data supports granting ofthepetition. Additional data maybe*,, neededbefore EPA rules on thepetition.

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### A.Residue Chemistry 1.Plant metabolism. The nature ofthe residues inplants is adequatelyunderstood for purposes ofthis tolerance petition. Metabolism studies infruit crops radish, tea and corn have been completed. The Agency has determined that the residues ofconcern are hexythiazox and its metabolites containing the (4-chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiety calculated as the stoichiometric equivalent ofhexythiazox. •• • • • • •

• ••• 4 • •2.Analytical method. The basic analytical method was previously reviewed by

the Agency in association with the establishment ofthe current tolerances with registrations ofmultiple commodities. The methods used in a new citrus raw agricultural commoditiesstudy are described fully in thestudy report which is submitted concurrently with this petition. 3. Magnitude ofresidues. The Agency previously has reviewed Magnitude of the Residuedata supporting toleranceswith regional registrations for citrus commodities (MRID 45898701, MRID 46330602, and MRID 46977001). Tolerances of0.35 ppm, 0.60 ppm, and 24 ppm currently are established for residues of hexythiazox in citrus group 10, fruit,citrus dried pulp, and citrus oil, respectively. New field trial data have been generated for hexythiazox on citrus. Four orange trials wereconducted in EPA Regions 6 (one trial) and 10 (threetrials) in 2013 and 2014. Three grapefruit trialswere conducted in Regions 6 (one trial)and 10 (two trials) in 2013 and 2014. Five lemon trials were conducted in Region 10 in 2013 and 2014. Side-by-side plots testing concentrate and dilutespray volumes were also established at one orangeand one grapefruit trial in Region 6 where only one trial is required. The results from these trials show that afterone application of Onager®lE Miticide at0.1875 lb ai/A (0.210 kg ai/ha) ± 5% residues ofhexythiazox ranged from 0.0392 to 0.0891 ppm (mean = 0.0631 ppm ± 0.0161) on ten orange RAC samplescollected 7 DAA and from 0.0222 to 0.0798 ppm (mean = 0.0484 ppm ± 0.0182) on ten orange RAC samples collected 14 DAA from the concentrated and dilute spray mixtureapplications. Residues ofhexythiazox ranged from <0.02 (LOQ) to 0.0853 ppm (mean = 0.0488 ppm ± 0.0268) on eight grapefruit RAC samples collected 7 DAA and from <0.02 (LOQ) to 0.0572 ppm (mean = 0.0377 ppm ± 0.0168) on eight grapefruit RACsamples collected 14 DAA from theconcentrated and dilute spray mixture applications. Residues ofhexjthiazox ranged from 0.102 to 0.257 ppm (mean = 0.184 ppm ± 0.0504) on ten lemon RAC samples collected 7 DAA and from 0.100 to 0.264 ppm (mean = 0.177 ppm ± 0.0483) on ten lemon RAC samples collected 14 DAA from theconcentrated and dilute spray mixture applications.
B. Toxicological Profile 1. Acute toxicity. A battery of acute toxicitj'studies places technical grade hexythiazox in Toxicity Category IV for acuteoral toxicitj' (LDso >5,000 mg/kg), **** Categoiy III foracute dermal toxicity (LDso >5,000 mg/kg). Category IIIfor acute,,*,; inhalation toxicity (LCso >2.0 mg/L), Categorj- III for primaiy- 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' studieswere conducted.These ar"[* a mammalian erythrocyte micronucleus test [NIRID 45480101], a mammalian cell

. forward gene mutation assay [MRID 00155154], a rat primaiy hepatocyte •••••• unscheduled DNA synthesis assay [MRID 00156893], a clastogenic evaluation in ^ in vitro cytogenetic assay measuring chromosomal aberration in Chinese hamster ** ovary cells [MRID 00156894], and an Amesstudy withSalmonella [MRID •• • • • •••••44955710]. All these mutagenicity tests were negative. 3. Reproductive anddevelopmental toxicity. In a developmental toxicity study with rats [MRID 00147578], the fetotoxicity NOELwas 240 mg/kg/day, and the compound was not embryotoxic at the highest dose tested,2160 mg/kg/day. In a developmental toxicity study with rabbits [MRID 00146555], no developmental toxicity- was observed at the highest dose tested, 1080 mg/kg/day. In a twogeneration reproduction study with rats [MRID 00147578 and 00151360], no reproductive effects were observed at 2400 ppm in the diet (^110 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 LOAELwas 12.5 mg/kg/day, based on increased liver and adrenal weights. 5. Chronic toxicity. In a 1-year feeding study in dogs, the NOAEL was 2.5 mg/kg/day and the LOAEL was 12.5 mg/kg/day, based on increased alkaline phosphatase, increased adrenal and liver weights, and liver and adrenal lesions. In acarcinogenicitj' study in mice, the NOAEL was 36 mg/kg/day and the LOAEL was 215 mg/kg/day. Effects weredecreased bodweight in males and increased hepatocellular carcinomas and combined adenoma/carcinomas.
In a chronic feeding/carcinogenicit\'study in rats, the NOAEL (systemic) was 26 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 2009 report 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 (RID) 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 be protective of all chronic effects including potential carcinogenicitj- ofhexythiazox. The CARC concluded that the evidence as a wholewas not strong enough to warrant the use pf*' 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. Animalmetabolism. The metabolism of hexjthiazox has been studied in * 1 plants. goats, hens and rats. Metabolic pathways in the animalare similarto those in I • • ••••

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 ofhexj'thiazox similar to effects produced by a naturally occurring estrogen, orother

endocrine effects is available from thetwo-generation rat reprodnction study, the rat and rabbit developmental studies and the rat and dog chronic studies. Thereis no evidence from these studiesthat hexythiazox induces estrogenic or other endocrine effects.
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, July 17, 2013, pages 42693-42699). 1.Food. Acute Exposure. No acuteendpoint has been identified in the toxicological studies for hexjthiazox; therefore, a quantitative acutedietary exposure assessment is unnecessarj'. Chronic Exposure.The Agency comprehensively evaluated potential dietary exposnre resnlting from the cnrrently registered uses ofhexy thiazox in the July 17, 2013 Federal Register. TheAgency concluded that chronic exposureto hexythiazox from food and water will utilize no more than 82% ofthe cPAD (for children 1-6 years old). The Agency's assessment employed tolerance residue values, the assumption of 100% crop treated and default processing factors. The proposed use of hexythiazox in citrus will not add appreciably to dietary risk. A tier 1chronic assessment shows a2.1% ofthe cPAD will be utilized by any population subgronp for the proposed use in citrus. ii. Drinking water. The Agency has previously used screening level snrface water exposure models in dietary exposnre analysis and risk assessment for hexythiazox in drinking water.Based on the Pesticide Root Zone Model /Exposure Analysis Modeling System (PRZM/EXAMS), theestimated drinking water concentration (EDWC) ofhexythiazox for chronic assessment was estimated to be 4.31 parts per billion (ppb). (Federal Register, .July 17, 2013, pages 42693-42699)
2. Non-dietary exposure. EPA has previously determined that potential residential exposures to hexythiazox are below levels of concern. D. Cumulative Effects • • •••• • • • • • •• •• EPA has not found that hexythiazox shares a common mechanism oftoxidt\i.!. • • • • • • with any other substances. *
E. Safety Determination • •• • • • •••••
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••••• • • •••••• 1. U.S.population. Acute risk. No adverse effect resulting from a single oral^ exposure to hexythiazox has been identified, thus hexythiazox is not expected to I 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 hexjthiazox. Chronic risk. The Agency previously concluded that no more than 82% of the cPAD would be utilized from the currently registered uses (food and water). The proposed increase in tolerances for citrus will utilize no more than an additional 2.1% ofthe cPAD. Chronic residentialexposure to the residues ofhexythiazox is not expected. 2. Infantsandchildren. EPA previously has determined that reliable data show the safety'ofinfants and children would be adequately protected ifthe FQPA SF were 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 exposureto hexv'thiazox residues.
F.International Tolerances The following maximum residue levels for hexy thiazox on citrus commodities have been established.


### Country Commodity Hexythiazox Tolerance (ppm)

Codex Citrus, Fruit 0.5 EU Citrus Fruits,Grapefruit,

Oranges, Lemons,Limes, Mandarins, Others 1.0

Japan Citrus (NATSUDAIDAL,

whole). Lemon Orange (including navel orange). Grapefruit,Lime, Other citrus fruits 2.0

Taiwan Citrus (including wholeTaiwan

crop group forcitrus) 1.0 •••• • • » • • •• ••

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