Document ID: EPA-HQ-OPP-2007-0495-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-08-01T04:00Z

Notice of Filing:  PP#7E7218

Registration Division contact: Barbara Madden; (703) 305-6463

Interregional Research Project Number 4 (IR-4)

PP# 7E7218

	EPA has received a pesticide petition (PP 7E7218) from Interregional
Research Project Number 4 (IR-4), 681 U.S. Highway #1 South, North
Brunswick, NJ 08902-3390 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
methoxyfenozide in or on the raw agricultural commodites avocado,
black-sapote, canistel, mamey sapote, mango, papaya, sapodilla, and star
apple at 0.6 parts per million (ppm); guava, feijoa, jaboticaba, wax
jambu, starfruit, passion fruit, and acerola at 0.4 parts per million
(ppm); green onion, fresh chive leaves, fresh Chinese chive leaves,
Elegans Hosta, Fritillaria leaves, kurrat, Lady’s leek, leek, wild
leek, Beltsville bunching onion, fresh onion, macrostem onion, tree
onion tops, Welsh onion tops, and fresh shallot leaves at 5.0 parts per
million (ppm). EPA has determined that the petition contains data or
information regarding the elements set forth in section 408 (d)(2) of
the 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. The qualitative nature of methoxyfenozide
residues in plants and animals is adequately understood. Residues in
plants, meat and fat are defined in terms of parent compound only.
Residues in eggs, liver and meat by-products (mbyp) are defined in terms
of combined residues of parent and its glucuronide metabolite, expressed
as parent. More details have been previously published in the Federal
Register of July 5, 2000 (65 FR 41355) (FRL-6497-5).>

<	2. Analytical method. Adequate enforcement methods are available for
determination of methoxyfenozide residues in plant commodities, based on
the Rohm and Haas Company Technical Report No. 34-98-87, “Tolerance
Enforcement Method for Parent RH-2485 in Pome Fruit”.  The available
Analytical Enforcement Methodology was previously reviewed in the
Federal Register of September 20, 2002 (67 FR 59193).>

<	3. Magnitude of residues. Complete residue data for methoxyfenozide on
avocado; guava; and green onions have been submitted by IR-4. The
requested tolerances are adequately supported.   >

<B. Toxicological Profile>

<	1. Acute toxicity. The toxicological profile and endpoints for
methoxyfenozide which supports this petition to establish tolerances
were previously published in the Federal Register of August 31, 2005 (70
FRL-7732-3).

>

		1. Acute toxicity.  NA

		2. Genotoxicty.  NA

		3. Reproductive and developmental toxicity.  NA

		4. Subchronic toxicity. NA

		5. Chronic toxicity. NA

		6. Animal metabolism. NA

		7. Metabolite toxicology. NA

		8. Endocrine disruption.  NA

<C. Aggregate Exposure>

<	1. Dietary exposure. Assessments were conducted to evaluate potential
risks due to chronic and acute dietary exposure of the U.S. population
subgroups to residues of methoxyfenozide.  These analyses cover all
registered crops, as well as, uses pending with the Agency, active and
proposed section 18 uses, and newly proposed IR-4 minor uses.  There are
no registered residential nonfood uses of methoxyfenozide.

 >

<	i. Food. a. Acute risk.  No appropriate toxicological endpoint
attributable to a single exposure was identified in the available
toxicology studies on methoxyfenozide including the acute neurotoxicity
study in rats, the developmental toxicity study in rats and the
developmental toxicity study in rabbits.  Since no acute toxicological
endpoints were established, the acute aggregate risk is expected to be
negligible.

b. Chronic assessments were conducted to evaluate potential risks due to
chronic dietary exposure of the U.S. population and sensitive population
subgroups to residues of methoxyfenozide.  The tier-1 assessment used
the Dietary Exposure Evaluation Model™ (DEEM-FCID, ver. 2.14,
Exponent, Inc., Washington, DC-20036) software for conducting the
chronic dietary (food) risk analysis.  DEEM is a dietary exposure
analysis system that is used to estimate exposure to a pesticide
chemical in foods comprising the diets of the U.S. population, including
population subgroups.  DEEM contains food consumption data as reported
by respondents in the USDA Continuing Surveys of Food Intake by
Individuals (CSFII) conducted in 1994-1996 and 1998 and food translation
to RACs, as indicated by EPA/USDA FCID recipe set as of August, 2002.  

None of the currently proposed uses are involving crops commonly used as
feed for livestock. Therefore, an estimated animal dietary burden is not
needed. 

The chronic tox-endpoint is the cRfD = 0.1 mg/kg-bw/day, published in
the Federal Register of August 31, 2005 (70 FRL-7732-3). The published
FQPA SF = 1x for methoxyfenozide and therefore the cPAD = 0.1 mg/kg/day.
The tier-I exposure was found to occupy up to 19.5% of the chronic
population adjusted dose (PAD) for US-general population and 42.8% of
PAD for the most highly exposed population subgroup, children 1 to 2
years old.  These results should be viewed as conservative (health
protective) risk estimates.  Refinements such as use of percent
crop-treated information and/or anticipated residue values would yield
lower estimates of chronic dietary exposure.

	ii. Drinking water. There are no water-related exposure data from
monitoring to complete a quantitative drinking water exposure analysis
and risk assessment for methoxyfenozide.  Screening level exposure
levels to water were estimated from EPA’s water models. Index Drinking
Water Reservoir model (FIRST) was used to calculate estimated the
environmental concentrations (EECs) for surface water. The screening
concentration in ground water was estimated by using the model Screening
Concentrations in GROund Water (SCI-GROW), an empirical model based upon
actual monitoring data collected for a number of pesticides that serve
as benchmarks. These models take into account the use patterns and the
environmental profile of a pesticide, but do not include consideration
of the impact that processing raw water for distribution as drinking
water would likely have on the removal of pesticides from the source
water.  The primary use of these models at this stage is to provide a
coarse screen for assessing whether a pesticide likely to be present in
drinking water at concentrations which would exceed human health levels
of concern.>

<

	A drinking water level of comparison (DWLOC) is the concentration of a
pesticide in drinking water that would be acceptable as a theoretical
upper limit in light of total aggregate exposure to that pesticide from
food, water, and residential uses.  HED uses DWLOCs internally in the
risk assessment process as a surrogate measure of potential exposure
associated with pesticide exposure through drinking water.  In the
absence of monitoring data for a pesticide, the DWLOC is used as a point
of comparison against the conservative EECs provided by computer
modeling (SCI-GROW, FIRST, GENEEC, PRZM/EXAMS).  The DWLOCs for
assessing chronic aggregate dietary risk can be back-calculated by
subtracting from the cRfD the amount of the estimated dietary exposure.
The methoxyfenozide’s DWLOC calculated for different sub-population
groups ranged between 0.6 to 2.8 ppm and it is much higher than the
highest EEC’s estimated by conservative tier-1 water models.>

<a.  Acute exposure and risk.  Because no acute dietary endpoint was
established, Dow AgroSciences concludes that there is a reasonable
certainty of no harm from acute exposure from drinking water.

b.  Chronic exposure and risk.   Tier I screening-level exposure
assessments was conducted using the simulation models SCI-GROW and FIRST
to generate EECs for ground and surface water, respectively.  The
modeling was conducted based on the environmental profile and the
maximum seasonal application rate proposed across current and proposed
labels The concentration used for chronic exposure from drinking-water
was estimated by the screening model FIRST as an annual average
concentration EEC = 15.8 parts per billion (ppb).

2. Non-dietary exposure. Methoxyfenozide is not currently registered for
use on any residential non-food sites.  Therefore, there is no
non-dietary acute, chronic, short- or intermediate-term exposure.>

<D. Cumulative Effects>

<		Section 408(b)(2)(D)(v) requires that, when considering whether to
establish, modify, or revoke a tolerance, the Agency consider
“available information” concerning the cumulative effects of a
particular pesticide’s residues and “other substances that have a
common mechanism of toxicity.”  

EPA does not have, at this time, available data to determine whether
methoxyfenozide has a common mechanism of toxicity with other substances
or how to include this pesticide in a cumulative risk assessment. 
Unlike other pesticides for which EPA has followed a cumulative risk
approach based on a common mechanism of toxicity, methoxyfenozide does
not appear to produce a toxic metabolite produced by other substances. 
For the purposes of this tolerance action, therefore, it is assumed that
methoxyfenozide does not have a common mechanism of toxicity with other
substances.>

<E. Safety Determination>

<	1. U.S. Population. Using the DEEM exposure assumptions described in
this unit, Dow AgroSciences has concluded that the aggregate exposure to
methoxyfenozide from the current and proposed new tolerances will
utilize 19.5% of the chronic PAD for the U.S. population.  If potable
water is aggregated to the dietary exposure, at the maximum residue
level estimated by EPA’s model FIRST (0.016 ppm), the aggregate
exposure to US-population is slightly increasing from to 19.8% PAD. EPA
generally has no concern for exposures below 100% of the chronic PAD
because the chronic PAD represents the level at or below which daily
aggregate dietary exposure over a lifetime will not pose appreciable
risks to human health.  Despite the potential for exposure to
methoxyfenozide in drinking water, the aggregate exposure is not
expected to exceed 100% of the chronic PAD.  Therefore, it can be
concluded with a reasonable certainty that no harm will result to
US-general population from aggregate exposure to methoxyfenozide
residues.>

<	2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of methoxyfenozide, EPA
considered data from developmental toxicity studies in the rat and
rabbit and a 2-generation reproduction study in the rat.  The
developmental toxicity studies are designed to evaluate adverse effects
on the developing organism resulting from maternal pesticide exposure
during gestation.  Reproduction studies provide information relating to
effects from exposure to the pesticide on the reproductive capability of
mating animals and data on systemic toxicity.  

FFDCA section 408 provides that EPA shall apply an additional ten-fold
safety factor for infants and children in the case of threshold effects
to account for prenatal and postnatal toxicity and the completeness of
the database unless EPA determines that a different margin of safety
will be safe for infants and children.  Margins of safety are
incorporated into EPA risk assessments either directly through use of a
margin of exposure (MOE) analysis, or through using uncertainty (safety)
factors in calculating a dose level that poses no appreciable risk to
humans.  EPA believes that reliable data support using the standard
uncertainty factor (UF = 100 for combined interspecies and intraspecies
variability) and no additional safety factor is required for the
calculation of MOE for any population sub-group. 

The toxicology data base available for methoxyfenozide included
acceptable developmental toxicity studies in both rats and rabbits as
well as a 2-generation reproductive toxicity study in rats.  The data
provided no indication of increased sensitivity of rats or rabbits to in
utero and/or postnatal exposure to methoxyfenozide.  There is a complete
toxicity data base for methoxyfenozide and the exposure data are
complete or are estimated based on data/assumptions that reasonably
accounts for potential exposures.  Based on the completeness of the data
base and the lack of prenatal and postnatal toxicity, EPA determined
that an additional safety factor was not needed for the protection of
infants and children (FQPA SF = 1x).

Since no acute toxicological endpoints were established, the acute
aggregate risk is considered to be negligible.  Using the exposure
assumptions described in this report, Dow AgroSciences has concluded
that chronic dietary exposure to methoxyfenozide from the existing and
proposed new tolerances will utilize at the most 42.8% of the cPAD for
infants and children.  If exposure from drinking water is aggregated to
the dietary exposure, at the maximum residue level estimated by EPA’s
model FIRST (0.016 ppm), the aggregate exposure to children 1-6 is
slightly increasing to 43.3 % PAD. EPA generally has no concern for
exposures below 100% of the cPAD because the cPAD represents the level
at or below which daily aggregate dietary exposure over a lifetime will
not pose appreciable risks to human health.  Short and intermediate term
risks are judged to be negligible due to the lack of significant
toxicological effects observed.  Based on these risk assessments, Dow
AgroSciences concludes that there is a reasonable certainty that no harm
will result to infants and children from aggregate exposure to
methoxyfenozide residues.>

<F. International Tolerances>

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y diverse good agricultural practices used for efficacious pest control,
different guidelines for conducting field crop residue studies and
different calculation methods to propose tolerances.   Based on the
current situation, the U.S. tolerance levels cannot be re-considered in
order to harmonize with MRLs from other countries, and therefore the
incompatibility will persist.>