Document ID: EPA-HQ-OPP-2008-0554-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-08-13T04:00Z

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE
PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

Docket ID No.: EPA-HQ-OPP-2008-0554

EPA Registration Division contact: Sidney Jackson (703-305-7610)

Interregional Research Project Number 4 (IR-4)

Pesticide Petition # 8E7347

******Note to Terri Stowe – Highlighted in the following paragraph is
a statement noting that the existing “cherry” tolerance can be
deleted with the establishment of  tolerances by this action and we will
make that deletion.  I believe you handled “deletion” actions under
a separate heading in previous NOF listings.  

EPA has received a pesticide petition (PP) # 8E7347 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, by establishing tolerances for residues of the
insecticide etoxazole,
2-(2,6-difluorophenyl)-4-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihy
drooxazole, in or on the following raw agricultural commodities: stone
fruit, crop group 12, except plum, at 1.0 parts per million (ppm), plum
at 0.12 ppm, plum, prune, dried at 0.4 ppm, cucumber at 0.02 ppm, tomato
at 0.25 ppm, spearmint tops  at 10 ppm, peppermint tops at 10 ppm,
peppermint oil at 20 ppm and spearmint oil at 20 ppm. The established
1.0 ppm tolerance for cherry may be deleted.  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                                       

. The metabolism of etoxazole is adequately understood for the purpose
of the proposed tolerances.

.  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.

.  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							

.  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).

.  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).

.   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. 

.  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. 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 for most registered
pesticides.

E. Safety Determination  

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.

.  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  

 PAGE  4 

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