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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: Reuben Baris, PM 25, 703

- 305

- 7356

Gowan Company

5F8355

EPA has received a pesticide petition ( 5F8355 ) 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.

by establishing a tolerance for residues of

E PTC, (S

- ethyl dipropylthiocarbamate) in or on the raw agricultural commodity Grass, grown for seed, forage at 0.6 parts per million (ppm) and G rass , grown for seed, hay at 0.5 ppm

. 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 fully evaluated the sufficiency of the submitted d a ta at this time or whether the data supports granting of the petition. Additional data may be needed befo re EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. EPTC is systemic and is rapidly metabolized in plants into numerous products. The Agency has determined that EPTC and three hydroxy metabolites 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 grass grown for seed. EPTC is analyzed by extraction of the samples with toluene with subsequent quantification using gas chromatography with nitrogen

- phosphorus detection. The three hydroxy metabolites are extracted from the samples with a mixture of acetone and water. The acetone is dispelled and the aqueous fraction is digested with acid. The hydrolyzed metabolites are then extracted with a mixture of hexane and ether, and the extract is purified through a solid phase extraction cartr idge. The residues are then derived and quantified using a gas chromatograph equipped with a mass

selective detector. The Limit of Quantification (LOQ) for EPTC was 0.05 ppm and 0.01 ppm for the hydroxy metabolites.

3. Magnitude of residues. Residues of EPTC and hydroxy metabolites ranged2

from <LOQ (0.0286 ppm) to 0.152 ppm on six ryegrass forage RAC samples

collected 29

- 30 DAA application. A permanent tolerance of grass grown for seed in grass, hay, of 0.5 ppm and grass, forage, of 0.6 ppm is propose d.

B. Toxicological Profile

1. Acute toxicity. EPTC is moderately toxic (Toxicity Category III) via the oral and dermal routes, and in primary eye irritation study in rabbits, the technical product was found to be slightly irritating (Toxicity Category III). EPTC is most

toxic via the inhalation route (Toxicity Category II).

2. Genotoxicty. Testing of EPTC for genotoxicity through an in vivo and in vitro assays indicated no concern.

3. Reproductive and developmental toxicity. Studies in rats and rabbits showed developmental and reproductive tox icity only in the presence of maternal or parental toxicity. In a prenatal developmental toxicity study in rats, developmental toxicity (in part, decreased fetal body weights and decreased litter size, but effects were attributed to maternal stress) was s een in the presence of marked maternal toxicity (increased mortality and decreased body weight). In developmental toxicity study in rabbits, developmental toxicity (decrease fetal body weight) was again seen in the presence of marked maternal toxicity (in part, decreased body weight and increased mortality). 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.

4. Subchronic toxicity. Cardiotoxicity a nd neurotoxicity were observed in subchronic studies in rats. Cardiotoxicity was attributed to myocardial degeneration by histological exam. The acute neurotoxicity study in the hen did not show neurotoxicity, however.

5. Chronic toxicity. Chronic te sting in rats and dogs also showed cardiotoxicity and neurotoxicity.

6. Animal metabolism. A study in rats indicated that EPTC was rapidly absorbed and excreted via radiolabeled product. Study indicates that only 1.2% of radiolabeled product was present in tissues after 7 days.

7. Metabolite toxicology

. The Agency has determined that metab olites incorporating the thiocarbamate moiety are of concern. These residues include various acid conjugates.

8. Endocrine disruption

. Per the Tier I test battery of the EDSP established by the Agency, EPTC does not indicate any endocrine disruptor ef fects.

C. Aggregate Exposure

1. Dietary exposure. Tolerances have been established in the 40 CFR 180.1173

for the residues of EPTC in or on a variety of raw agricultural commodities. Risk assessments were performed to assess dietary exposures from EPTC in food as

follows:

i. Food. Results of the aggreg ate dietary exposure assessment for all uses

indicate that the estimated risks are below the level of concern for both acute and chronic dietary per the following EPA document, EPTC: Registration Review Scoping Document for Human Health Assessment, March 5 , 2013, DP Barcode D405957, pg 2 of 23.

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 incom plete information regarding developmental neurotoxicity, EPA has retained the 10X FQPA Safety Factor.

E. Safety Determination

1. U.S. population. The proposed grass for seed use of EPTC results in exposures to the general population and all subpopulat ions that are within acceptable ranges.

2. Infants and children

. [ Risk calculations for the proposed grass for seed use result in acceptable exposures. The Agency retained a 10X Safety Factor in the toxicological endpoints for EPTC which was included in the calculation of

exposures.

F. International Tolerances

There are no international Tolerances/ MRLs currently established for

EPTC.