Document ID: EPA-HQ-OPP-2009-0836-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-02-04T05:00Z

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,703-305-5697

Gowan Company

[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 by 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 fully evaluated
the sufficiency of the submitted data at this time or whether the data
supports granting of the petition. Additional data may 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 EPTC 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.  EPTC is moderately toxic (Toxicity Category 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. 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. There does not appear to be
concern about the reproductive or 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 described 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 acute 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 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.  Therefore, EPTC tolerances 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 risk assessment as no
residues are expected in meat or milk. 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
whether 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 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 MRLs currently established for EPTC.