EPA REGISTRATION DIVISION - COMPANY NOTICE OF 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 Number (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

conversion of the existing Fruit, citrus, group 10 tolerance at 0.1 ppm to Fruit, citrus

group 10-10 at 0.1 ppm and conversion 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 sufficiency 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 extracted 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 0.01 ppm for each of three hydroxy metabolites.
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3. Magnitude of residues. Residues 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. EPTC is moderately 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 (Toxicity 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 rabbits 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 effects 

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 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 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 neurotoxicity, 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 metabolites 

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.
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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 analysis 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 redefined 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 general population from 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 children 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. Exposures by non-dietary means were determined to 

be not of concern in the EPTC Reregistration Eligibility Decision (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 watermelon use for EPTC results in 

exposures to the general population and all subpopulations that are within 

acceptable ranges.

2. Infants and children. Risk calculations for the proposed watermelon use 

result in acceptable exposures. The Agency has retained a 10X FQPA safety factor 

in the toxicological endpoints for EPTC which was included in the calculation of 

exposures.

F. International Tolerances
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There are no international Maximum Residue Limits (MRLs) currently 

established for EPTC.