Document ID: EPA-HQ-OPP-2010-0063-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2010-05-19T04:00Z

EPA Registration Division contact: Andrew Ertman, (703) 308-9367

Interregional Research Project Number 4 (IR-4)

PP #9E7675

		

	

EPA has received a pesticide petition (PP #9E7675)  from Interregional
Research Project Number 4 (IR-4), IR-4 Project Headquarters, Rutgers,
The State University of New Jersey, 500 College Road East, Suite 201 W,
Princeton, NJ  08450, 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 180.593, by establishing a tolerance for residues of
the chemical etoxazole,
2-(2,6-difluorophenyl)-4-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihy
drooxazole, in or on the following raw agricultural commodities: 
peppers, African eggplant, eggplant, martynia, okra, pea eggplant,
pepino, roselle, and scarlet eggplant at 0.20 parts per million (ppm);
Crop Group 9: Cucurbit Vegetables at 0.20 ppm; Subgroup 13-07A:
Caneberry at 1.1 ppm; Subgroup 13-07F: Small fruit vine climbing
subgroup except fuzzy kiwi at 0.50 ppm; Subgroup 13-07G: Low-growing
berry subgroup at 0.50 ppm and avocado, papaya, star apple, black
sapote, mango, sapodilla, canistel, and mamey sapote at 0.20 ppm; and
tea at 15 ppm.

Additionally, the petitioner proposes to delete the established
tolerances for strawberry, grape, cucumber, and vegetable, cucurbit
subgroup 9A since they will be covered by the proposed new tolerances in
this action.

EPA has determined that the petitions contain data or information
regarding the elements set forth in section 408(d)(2) of the FFDCA;
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. The metabolism of etoxazole is adequately
understood for the purpose of the proposed tolerances.

	2.  Analytical method.  Practical analytical methods for detecting and
measuring levels of etoxazole have been developed and validated in/on
all appropriate agricultural commodities and respective processing
fractions.  The LOQ of etoxazole in the methods is 0.02 ppm which will
allow monitoring of food with residues at the levels proposed for the
tolerances.

	3. Magnitude of residues.  Residue data have been submitted which
adequately support the requested tolerance. 

B. Toxicological Profile

	The toxicological profile for etoxazole which supports this petition
for tolerances was published in the Federal Register on September 26,
2003 (68 FR 55485)(FRL-7324-8).

C. Aggregate Exposure

	1. Dietary exposure.  A chronic dietary analysis was conducted to
estimate exposure to potential etoxazole residues in/on the following
crops: cotton, fruit, pome (Crop Group 11), strawberry, tangerines, nut,
tree (Crop Group 14), pistachios, grapes, hops, and mint. The addition
of the proposed uses to the approved uses of etoxazole is expected to
make a negligible incremental risk to the dietary risk assessment
conducted and therefore, the assessment has not been repeated to include
these minor uses.

The Cumulative and Aggregate Risk Evaluation System (CARES) Version 2.0
was used to conduct these assessments.  This Tier I assessment used
issued and proposed tolerances, default processing factors, and the
assumption of 100% crop treated.  No adjustments were made for common
washing, cooking or preparation practices. Exposure estimates for water
were made based upon modeling (FIRST and SCI-GROW).

	i. Food.  a. Acute-An endpoint of concern attributable to a single oral
dose was not selected for either the general U.S. population (including
infants and children) or the female 13-50 years old population subgroup.
 Therefore, quantitation of the acute risk is not required.

	b.  Chronic-The chronic dietary exposure estimate of etoxazole residues
in food was calculated to be, at most, 15.2% of the chronic Population
Adjusted Dose (c-PAD) with a MOE of 6500.  The population subgroup with
the highest exposure was children 1-2 years old.  The c-PAD was defined
as the NOEL from a dog chronic oral toxicity study and includes an
uncertainty factor of 100 to account for intra- and inter-species
variation  (NOEL = 4.62 mg/kg bw/day, c-PAD = 0.046 mg/kg/day).

	ii. Drinking water.   Since etoxazole is applied outdoors to growing
agricultural crops, the potential exists for the parent or its
metabolites to reach ground or surface water that may be used for
drinking water. Because of the physical properties of etoxazole, it is
unlikely that etoxazole or its metabolites can leach to potable
groundwater. To quantify potential exposure from drinking water, surface
water concentrations for etoxazole were estimated using FIRST and
SCI-GROW models. The annual average surface water concentration of
etoxazole and its metabolites was predicted to be 1.77 ppb.  Chronic
exposure from this drinking water would be 0.0000506 and 0.000177
mg/kg/day for adults and children, respectively; 0.38% of the c-PAD of
0.046 mg/kg/day for children.  Based on this worse case analysis, the
contribution of drinking water is negligible. 

	2. Non-dietary exposure.  Etoxazole is proposed only for agricultural
uses and no homeowner or turf uses. Thus, no non-dietary risk assessment
is needed. 

	

D. Cumulative Effects  

Section 408(b)(2)(D)(v) requires that the Agency must consider
“available information'' concerning the cumulative effects of a
particular pesticide's residues and ``other substances'' that have a
common mechanism of toxicity. Available information in this context
include not only toxicity, chemistry, and exposure data, but also
scientific policies and methodologies for understanding common
mechanisms of toxicity and conducting cumulative risk assessments. For
most pesticides, although, the Agency has some information in its files
that may turn out to be helpful in eventually determining whether a
pesticide shares a common mechanism of toxicity with any other
substances, EPA does not at this time have the methodologies to resolve
the complex scientific issues concerning common mechanism of toxicity in
a meaningful way.

     In consideration of potential cumulative effects of etoxazole and
other substances that may have a common mechanism of toxicity, there are
currently no available data or other reliable information indicating
that any toxic effects produced by etoxazole would be cumulative with
those of other chemical compounds. Thus, only the potential risks of
etoxazole have been considered in this assessment of aggregate exposure
and effects.

E. Safety Determination  

	1. U.S. population. i.  Acute Risk. No acute endpoint has been
identified the general U.S. population. Therefore, no assessment of
acute exposure from food to this subgroup is required.

	ii.  Chronic Risk.  The potential chronic exposure from food to the
U.S. Population and various non-child/infant population subgroups will
utilize at most 2.8% of the c-PAD.  Addition of the worse case, dietary
exposure from water (0.0000506 mg/kg/day) has no effect on this
exposure.  The Agency has no cause for concern if total chronic residue
contribution is less than 100% of the c-PAD, because the PAD represents
the level at or below which daily aggregate exposure over a lifetime
will not pose appreciable risk to human health.  Therefore, it can be
concluded that there is a reasonable certainty that no harm will result
to the overall U.S. Population from aggregate, chronic exposure to
etoxazole residues.

	2. Infants and children.  i. Safety Factor for Infants and Children. In
assessing the potential for additional sensitivity of infants and
children to residues of etoxazole, FFDCA section 408 provides that EPA
shall apply an additional margin of safety, up to ten-fold, for added
protection for infants and children in the case of threshold effects
unless EPA determines that a different margin of safety will be safe for
infants and children.  The toxicological data base for evaluating
prenatal and postnatal toxicity for etoxazole is complete with respect
to current data requirements.  There are no special prenatal or
postnatal toxicity concerns for infants and children, based on the
results of the rat and rabbit developmental toxicity studies or the
2-generation reproductive toxicity study in rats. EPA has concluded that
reliable data support use of the standard 100-fold uncertainty factor
and that an additional uncertainty factor is not needed for etoxazole to
be further protective of infants and children.

	ii. Acute Risk. No acute endpoint has been identified for infants and
children. Therefore, no assessment of acute exposure from food to this
subgroup is required.

	iii.  Chronic Risk.  The potential chronic exposure from food to
children 1-2 years old (the most highly exposed child/infant subgroup)
will utilize at most 15.2% of the c-PAD.  Addition of the worse case,
dietary exposure from water (0.000177 mg/kg/day) increases this exposure
to 15.6% of the c-PAD.  Therefore, it can be concluded that there is a
reasonable certainty that no harm will result to infants and children
from aggregate, chronic exposure to etoxazole residues.

F. International Tolerances  

Etoxazole has not been evaluated by the JMPR and there are no codex
maximum residue limits (MRL) for etoxazole. MRL values have been
established for etoxazole in the following countries: Turkey, Israel,
South Africa, Japan, France, Taiwan, and Korea. The use pattern and
MRL's are similar to those proposed for the U.S.