EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE

PETITIONS PUBLISHED IN THE FEDERAL REGISTER Tolerance Petition for EPTC in Forage and Hay of Grass Grown for Seed EPA Registration Division contact: Jim Tompkins,703

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- 5697 Gowan Compan y [9F7620] EPA has received a pesticide petition ( [ 9F7620 ] ) from Gowan Company , 370 S. Main Street, Yuma, AZ 85364 , 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 b y establishing a tolerance for residues of S

- Ethyl dipropylthiocarbamate in or on the raw agricultural commodity grasses grown for seed at 0.1 parts per million (ppm) for hay and 0.2 parts per million (ppm) for forage. 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 full y evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data m ay be needed before EPA rules on the petition. A. Residue Chemistry
1. Plant metabolism. EPTC is systemic and rapidly metabolized in plants. Based on results of acceptable plant metabolism studies, the Agency has determined that EPTC and three hydroxy metabolites, EPTC sulfoxide, EPTC sulfone, and glutathione conjugate of the sulfone metabolite will serve as markers to represent EPTC residues in plants. 2. Analytical method. Adequate methods are available for the determination of EPTC and three hydroxy metabolites in crops, including grass grown for seed. The EPA reviewed these methods and noted in the 1999 EPTC Reregistration Eligibility Decision (RED) that methods are available and adequate. The Limit of Quantitation of the methods is 0.05 ppm for E PTC and 0.01 ppm for each of the hydroxy metabolites. 3. Magnitude of residues. Maximum residues of EPTC and metabolites in hay and forage in three applicable MOR trials were 0.0819 ppm for hay and 0.152 ppm for forage. A permanent tolerance of 0.1 ppm for hay and 0.2 for forage are proposed and adequately supported for use in cool season grasses grown for seed in the Pacific Northwest (Washington, Oregon and Idaho). B. Toxicological Profile 1. Acute toxicity. EP TC is moderately toxic (Toxicity Cate gory III) via the oral and dermal routes, and in a primary eye irritation study in rabbits, the technical was found to be slightly irritating (Toxicity Category III). EPTC is most toxic via the inhalation route (Toxicity Category II). 2. Genotoxicty. Tes ting of EPTC for genotoxicity through an in vivo micronucleustest and a Drosophila sex - linked recessive lethal mutation assay gave negative results.

3. Reproductive and developmental toxicity. There does not appear to be concern about the reproductive o r developmental toxicity of EPTC. Studies in rats and rabbits showed developmental and reproductive toxicity only in the presence of maternal or parental toxicity. In a two generation reproduction test in rats, effects in the offspring were observed only at or above treatment levels which resulted in parental toxicity. Although EPTC did not produce any significant reproductive or developmental toxicity, the Agency recommended a 10X safety factor be applied for potential exposure to infants and children in residential use.

4. Subchronic toxicity. An acceptable subchronic study was reviewed by EPA and established a NOAEL at 600ppm (15 mkg/kg/day) in male dogs and 1800 ppm (45 mg/kg/day) in females. The LOAEL for In two chronic/oncogenicity feeding studies and in 90 - day feeding and inhalation studies, all rats exhibited myocardial degeneration during the histopathology examination (Mackenzie, 1986; U.S. EPA, 1999). In dogs, two chronic oral dosing studies revealed degenerative changes in the cardiac muscle when EPTC was administered in a capsule, but not when it was administered at comparable doses in the diet. Electrocardiograms were performed in both dog studies; however, only one high - dose male in the capsule study exhibited changes which were desc ribed as "potentially" treatment- related (U.S. EPA, 1999) 5. Chronic toxicity. Cardiotoxicity and neurotoxicity were observed in subchronic studies in rats. Cardiotoxicity was attributed to myocardial degeneration by histological exam. However, the acu te neurotoxicity study in the hen did not show neurotoxicity. The Agency’s FQPA Safety Factor Committee recommends that a 10X safety factor be retained for all population subgroups for acute, chronic and residential exposure assessments. 6. Animal metab olism. The metabolism of EPTC in rats was studied using radiolabeled EPTC. Most of the radioactivity was quickly excreted in the urine and there was little accumulation in tissues. Small amounts were excreted in the feces by exhalation. No sex- linked difference in metabolism or distribution of EPTC was noted. 7. Metabolite toxicology

. The Agency has determined that metabolites incorporating the thiocarbamate moiety are of concern. These residues include various acid conjugates. Therefore, EPTC tolera nces are based on residue data of EPTC and its hydroxylated metabolites. 8. Endocrine disruption

. There is no evidence of endocrine disruptor effects in the EPTC database. C. Aggregate Exposure 1. Dietary exposure. Tolerances have been established in 40 CFR 180.117 for the residues of EPTC in or on a variety of raw agricultural commodities. The addition of the proposed use on cool season grasses grown for seed would not affect the current EPA riskassessment as no residues are expected in meat or mil k. Risk assessments were performed

to assess dietary exposures from EPTC in food as follows: i. Food. Acute and chronic risk from food does not exceed the Agency's level of concern. In both assessments, exposure (consumption) was compared to a population adjusted dose (PAD) reflecting retention of the FQPA 10x factor. The PAD is equal to the acute or chronic RfD divided by the FQPA Safety Factor. The Agency considers dietary residue contributions greater than 100% of the PAD to be of concern. Acute dietary exposure comprised 40.5% of the aPAD for the general population, and 87.5% of the aPAD for the most highly exposed subgroup, children (1 - 6 years). Chronic dietary exposure comprised 9.6% of the cPAD for the general population, and 17.4% of the cPAD for the most highly exposed subgroup, children (1 - 6 years). Acute dietary risk analysis demonstrates acceptable food risk to the US population and all dietary subgroups. The acute dietary Margin of Exposure for the general population remains approximately 9000 based on a Tier 1 DEEM- FCID analysis as the proposed use will not affect dietary risk. EPTC residues in milk and meat “represents a Category 3 situation under 40CFR §180.6(a): i.e., a situation in which it is not possible to establish with certainty whet her finite residues will be incurred under reasonable worst- case exposure scenarios, but there is no reasonable expectations of the occurrence of finite residues in animal commodities.” ii. Drinking water. Estimation of drinking water levels for EPTC did not result in levels of concern. 2. Non

- dietary exposure

. Exposures by non - dietary means were determined to be not of concern in the EPTC RED. D. Cumulative Effects The Agency has determined that thiocarbamates cannot be regulated as a single class due to differing neurotoxic activity patterns. Due to incomplete information regarding developmental neurotoxicity, EPA has retained the 10X FQPA Safety Factor. E. Safety Determination 1. U.S. population. The proposed use of EPTC on cool season grasses grown for seed use results in exposures to the general population and all subpopulations that are within acceptable ranges. 2. Infants and children

. Risk calculations for the proposed grass grown for seed use result in acceptable exposures. The Agency h as retained a 10X FQPA safety factor in the toxicological endpoints for EPTC which was included in the calculation of exposures. F. International Tolerances There are no international MRLs currently established for EPTC.