 

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. 

	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.

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

	There are no international Maximum Residue Limits (MRLs) currently
established for EPTC.

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