**EPA REGISTRATION DIVISION -**  **COMPANY NOTICE O F**  **FILING FOR**

**PESTICIDE PETITION Docket ID Number: EPA** **- HQ**  **- OPP**  **- 2011**  **- 1011**  **EPA Registration**  **Division contact: Sidney Jackson (703) 305**  **- 7610**  **Interregional Research Project Number 4**  **(IR -**  **4) Pesticide Petition N**  **umber (PP#): 1E7951**  EPA has received a pesticide petition **( PP)**  **, 1E7951**  **,** from the **IR -**  **4 Project**  **Headquarters, Rutgers,**  **The State University of NJ, 500 College Road East, Suite 201 W, Princeton, NJ 08540**  **,** 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 the **herbicide S -**  **ethyl dipropylthiocarbamate (EPTC)**  , including its metabolites and degradates , in or on the raw agricultural commodity; **watermelon** at **0. 08**  parts per million (ppm) . The petition also requests **conver sion of**  **the existing**  **Fruit, citrus, group**  **10 tolerance**  **at 0.1 ppm**  **to Fruit,**  **citrus group**  **10 -**  **10 at 0.1 ppm**  **and c**  **onver sion of existing**  **safflower and**  **sunflower tolerance**  **at 0.08 ppm to Sunflower subgroup**  **20B at 0.08 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 suffici ency of the submitted data at this time or whether the data support granting of the petition. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry 1. Plant metabolism. **EPTC is systemic pesticide**  **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 crops, including watermelon**  **. EPTC is**  **analyzed by extraction of the macerated samples with toluene with subsequent quantification using gas chromatography with nitrogen**  **- phosphorous**  **detection. The three hydroxy metabolites are extra**  **cted from macerated 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 cartridge. The**  **residues are then derivatized and quantified using a gas chromatograph equipped with a mass**  **- selective detector. The Limit of Quantitation of the methods is 0.05**  **ppm for EPTC and 0. 0**  **1 ppm for each of**  **th re**  **e hydroxy metabolites.** 2 3. Magnitude of residues. **Re sidues of EPTC and metabolites**  **were undetectable (<0.08 ppm)**  **in watermelon**  **in seven**  **applicable MOR trials. A permanent tolerance of 0.**  **08 ppm is proposed.**  B. Toxicological Profile 1. Acute toxicity. **EP TC is m**  **oderately toxic (Toxicity Category III) via the oral and**  **dermal routes, and in a 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 (Toxici ty Category II).**  2. Genotoxicty. **Testing of EPTC for genotoxicity through an in vivo**  **micronucleus test and a Drosophila sex** **- linked recessive lethal mutation assay gave**  **negative results.** 3. Reproductive and developmental toxicity. **Studies in rats and ra bbits showed**  **developmental and reproductive toxicity 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 ef**  **fects were attributed to maternal stress) was seen in the presence of marked maternal**  **toxicity (increased mortality and decreased body weight). In a developmental**  **toxicity study in rabbits, developmental toxicity (decreased fetal body weight ) was**  **again se en 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 tox icity.**  4. Subchronic toxicity. **Cardiotoxicity and 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**  **neurotoxic ity** **, however.** 5. Chronic toxicity. **Chronic testing in rats and dogs also showed cardiotoxicity and neurotoxicity.**  6. Animal metabolism. **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 metabo lites**  **incorporating the thiocarbamate moiety are of concern. These**  **residues include**  **various acid conjugates.** 8. Endocrine disruption

. **There is no evidence of endocrine disruptor effects in the EPTC database.** 3

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. Risk**  **assessments were performed to assess dietary exposures from EPTC in food as follows:**  i. Food. **Acute dietary risk analy sis demonstrates acceptable food risk to the**  **US population and all dietary subgroups. The acute dietary Margin of Exposure for the general population**  **exceeded 9000**  **(based on the 95% -** **ile estimate) with and**  **without the proposed watermelon**  **use and the redefi**  **ned citrus and oilseed subgroups**  **based on a Tier 1 DEEM -**  **FCID analysis. The lowest acute MOE with or**  **without watermelon**  **use was 3880**  **for children 1 -**  **2 years old. A Tier 3 chronic risk assessment showed an increase in the %cPAD for the gene**  **ral population fr om 6.2%**  **to 13.0% with an assumption of 100% of the watermelon crop treated . The highest**  **%cPAD use for current labeled uses was 13.7% for chi ldren 1**  **- 2 years old but was**  **30.8 % with the**  **watermelon use**  **included for children 3 -**  **5 years old . The large**  **increase in the chronic risk estimate**  **is due to a conservative assumption of 100% crop treated for the proposed**  **watermelon use.**  ii. Drinking water

. **Estimation of drinking water levels for EPTC did not result in levels of concern.**  2. Non

- dietary exposure

. **Exposu res by non**  **- dietary means were determined to**  **be not of concern in the EPTC R eregistration**  **E ligibility**  **D e**  **c ision**  **(RED) .**  D. Cumulative Effects **The Agency has determined that thiocarbamates cannot be regulated as a single class due to differing neurotoxic ac** **tivity patterns. Due to incomplete information regarding developmental neurotoxicity, EPA has retained the 10X**  **FQ PA Safety Factor.**  E. Safety Determination 1. U.S. population. **The proposed watermelon**  **use for EPTC results in**  **exposures to the general popul ation and all subpopulations that are within**  **acceptable ranges.**  2. Infants and children

. **Risk cal culations for the proposed watermelon**  **use result in acceptable exposures. The Agency has retained a 10X FQPA safety factor**  **in the toxicological endpoints fo r EPTC**  **which was included in the calculation of exposures.**  F. International Tolerances4 **There are no international Maximum Residue Limits (** **MRLs )**  **currently established for EPTC.**