EPA REGI STERED DIVI SI ON COMPANY NOTI CE OF FILING FOR PESTI CI DE

PETI TI ONS PUBLISHED IN THE FEDERAL REGI STER. EPA Registration Division contact: Mark Suarez, PM 13, (703) 305 - 0120 Gowan Compan y **[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) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180. 1. by establishing a tolerance for residues of Hex ythiazox (trans - 5 - (4 - chlorophen yl l) - N - cy clohexyl - 4 - methy l - 2 - oxothiazolidine - 3 - carboxamide) in or on the raw agricultural commodity sorghum , grain at 3 parts per million (ppm); sorghum , grain, forage at 5 ppm; and sorghum, grain, stover at 6 ppm. EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of the FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted dat a 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. The nature of the residues in plants is adequatel y understood for purposes of this tolerance. Metabolism studies in fruit crops, radish , tea and corn have been completed . The Agency has determined that the residues of concern are hex ythiazox and its metabolites containing the (4 - chlorophen yl ) - 4 - methyl - 2 - oxo - 3 - thiazolidine moiety . 2. Analytical method. A practical anal yt ical method, high pressure liquid chromatograph y with a UV detector, which detects and measures residues of hexy thiazox and its metabolites as a common moiety , is available for enforcement purposes with a limit of detection that allows monitoring of food with residues at or above the levels set in this tolerance. 3. Magnitude of residues. Eight n ew field trials were conducted by Gowan Company in support of the proposed label amendments for sorghum (grain) . The amendments include regional (Western US) use of hexy thiazox on sorghum (grain) . The results of these new trials support the proposed tolerance levels: sorghum , grain 3 ppm; sorghum, grain, forage 5 ppm; and sorghum , grain , stover 6 ppm .B. Toxicological Profile 1. Acute toxicity. A battery of acute toxicity

studies places technical grade hex ythiazox in Toxicity

Category I V for acute oral L D50 (LD50 > 5,000 milligram/kilograms (mg/kg)), Category III for dermal LD50 (LD50 > 5,000 mg/kg), Category III for inhalation L C50 (LC50 >2.0 mg/L), Category III for primary

ey e irritation (showed mild irritation (reddened conjunctiva)), Category I V for dermal irritation (non irritant). Hex ythiazox is a non - sensitizer. Acute toxicologica l studies place technical grade hex ythiazox in Toxicology Category I II. 2. Genotoxicty. The following genotoxicity studies were all negative: Ames gene mutation, CHO gene mutation, CHO chromosome aberration, mouse micronucleus and rat hepatocy

te unsche duled DNA s ynthesis. 3. Reproductive and developmental toxicity. Ina developmental toxicity study in rats, the maternal No - Adverse - Effect - Level (NOAEL) was 240 mg/kg/day and the maternal Lowest - Adverse - Effect - Level (LOAEL) was 720 mg/kg/day based on inc reased ovarian weights and decreased bone ossification. In a developmental toxicity stud y in rabbits, the maternal NOAELwas 1,080 mg/kg/day (HDT); the maternal LOAEL was not determined. The developmental NOAEL was 1,080 mg/kg/day (HDT); the developmental LOAEL was not determined. In a 2 - generation reproduction study in rats, the parental NOAEL was 35 mg/kg/day and the parental LOAEL was 200 mg/kg/day based on decreased bod y weight gain, decreased food consumption and efficiency , and increased liver, kidne y and ovarian weights. The reproductive NOAEL was 35 mg/kg/day and the reproductive LOAELwas 200 mg/kg/day based on decreased pup b ody weight during lactation, delay ed hair growth and ey e opening. 4. Subchronic toxicity. Ina 1 - month feeding stud y 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. Ina 1 - ye ar feeding stud y in dogs, the NOAEL was 2.5 mg/kg/day

and the LOAELwas 12.5 mg/kg/day , based on increased al kaline phosphatase, increased adrenal and liver weights, and liver and adrenal lesions. In a carcinogenicity

study in mice, the NOAEL was 36 mg/kg/day and the LOAELwas 215 mg/kg/day . Effects were decreased bod y weight in males and increased hepatocellul ar carcinomas and combined adenoma/carcinomas. In a chronic feeding/carcinogenicit y stud y in rats, the NOAEL (s ys temic) was 26 mg/kg/day

and the LOAEL(s ys temic) was 180 mg/kg/day based on decreased body weight gain and increased liver weights in both s exes. A 2009 report from the Cancer Assessment Review Committee (CARC) (September 02, 2009, PC Code 128849, TXR 0055255) noted that the NOAEL of 2.5 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 inducedtumors. Thus, the chronic RfD of 0.025 mg/kg/day would be protective of all chronic

effects including potential carcinogenicity of hexythiazox. The CARC concluded that the e vidence as a whole was not strong enough to warrant the use of a linear low dose extrapolation model applied to the animal data (Q1*) for a quantitative estimation of human risk, as had been previously assessed in October 16, 1998, [63.FR55540]. 6. Anima l metabolism. The metabolism of hex ythiazox has been studied in goats, hens and rats. Metabolic pathway s in the animal are similar to those in plants. 7. Metabolite toxicology . There are no metabolites of toxicological concern based on a differential metabolism between plants and animals. 8. Endocrine disruption . No specific test s have been conducted with hexy thiazox to determine whether the chemical may have an y effect in humans that is similar to an effect produced b y a naturally oc c urring estrogen or other endocrine effects. However, there were no significant findings in other relevant toxicity tests, i.e., teratology

and multi - generational reproduction studies, which would suggest that hex ythiazox produces effects characteristic of the disruption s of hormones. C. Aggregate Exposure 1. Dietary exposure. Dietary Exposure from food. A dietary risk assessment for all registered crops has been completed b y the Agency ( December 14, 2011, FR Doc No. 2011 - 32086 ) i. Food. Acute Exposure . No acute endpoint has been identified in the toxicological studies for hexy thiazox; therefore, a quantitative acute dietary exposure assessment is unnecessary . Chronic Exposure . A tier 1 chronic risk assessment by Gowan Company indicates that the proposed use resu lts in a dietary risk of not more than 6 8.5 % of the chronic Population Adjusted Dose (cPAD) for an y population. ii. Drinking W

ater . The Agency

used screening level water exposure models in the dietary

exposure analy sis and risk assessment for hexy thiazox in drinking water. Based on the Pesticide Root Zone Model /Exposure Anal ys is Modeling System (PRZM/EXAMS) the estimated drinking water concentration (EDWC) of hexy thiazox for chronic exposures for non - cancer and cancer assessments is estimated to be 4. 5 parts per billion (ppb) for surface water. Since surface water residue values greatly exceed groundwater EDWCs, surface water residues were used in the dietary risk assessment . 2. Non - dietary exposure . HED has conducted a residential risk assessment to s upport approved uses on turf, ornamental landscape plantings, ornamental plants, orchids and residential fruit trees, nut trees and caneberries. The Agency conclude d that there we re no residential risks of concern associated with these uses (January 28, 20 10 EPA Memo. PR Code: 128849, DP Barcode D372889.)D. Cumulative Effects

EPA has not found that hex ythiazox shares a common mechanism of toxicity with an y other substance. E. Safety Determination 1. U.S. population. Acute risk . No adverse effect resulting from a single oral exposure to hex ythiazox has been identified, thus hexy thiazox is not expected to pose an acute risk. Short - and intermediate term risk . EPA has concluded the combined short - term food, water, and residential exposures result in a ggregate MOEs of 1 4 ,000 for adults and 1,9 00 for children. Because EPA's level of concern for hex ythiazox is a MOE of 100 or below, these MOEs are not of concern. Chronic risk . Chronic exposure to hex ythiazox from food and water will utilize no more than 6 8.5 % of the cPAD for the population group receiving the greatest exposure (children 1 - 2 y ears old) . This assessment utilized existing tolerance values, assumed 100% crop treated, and utilized default processing factors. Chronic residential exposure to re sidues of hex ythiazox is not expected. 2. Infants and children . 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 hexy thiazox residues. F. International Tolerances No national or transnational maximum residue levels for hex ythiazox exist apart from those in the United States.