Document ID: EPA-HQ-OPP-2007-0495-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-10-24T04:00Z

COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE  (9/27/2007)

EPA Registration Division contact: [Barbara Madden, (703) 305-6463]

 

INSTRUCTIONS:  Please utilize this outline in preparing tolerance
petition documents.  In cases where the outline element does not apply
please insert “NA-Remove” and maintain the outline.  The comment
notes that appear on the left margin represent hidden typesetting codes
designed to expedite the processing of the Federal Register document. 
Please do not remove or alter these comment notes or change the margins,
font, or format in your document. Simply replace the instructions that
appear in italics and brackets, i.e., “[insert company name],” with
the information specific to your action.]

TEMPLATE:

[Dow AgroSciences LLC]

[0F6201]

	EPA has received a pesticide petition ([0F6201]) from [Dow AgroSciences
LLC], [9330 Zionsville Road –Indianapolis, Indiana 46268] 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.

(Options (pick one)

	1. to reestablish the time-limited tolerances for indirect or
inadvertent residues of

	2. to establish an exemption from the requirement of a tolerance for

[methoxyfenozide and its metabolites RH-117,236 free phenol of
methoxyfenozide; 3,5-dimethylbenzoic acid N-tert-butyl-N'-(3-hydroxy-
2-methylbenzoyl) hydrazide, RH-151,055 glucose conjugate of RH-117,236;
3,5-dimethylbenzoic acid N-tert-butyl-N-[3(
-[beta]-D-glucopyranosyloxy)-2-methylbenzoyl]-hydrazide) and RH-152,072
the malonylglycosyl conjugate of RH-117,236] in or on the raw
agricultural commodities [Vegetable, root and tuber, group 1 at 0.1
parts per million (ppm); Vegetable, leaves of root and tuber, group 2 at
0.2 ppm; Vegetable, bulb, group 3 at 0.2 ppm; Vegetable, legume, group 6
at 0.1 ppm; Vegetable, foliage of legume, group 7 at 10 ppm; Grain,
cereal, forage, fodder, and straw, group 16 at 10 ppm; Grass, forage,
fodder and hay, group 17 at 10 ppm; Animal feed, non-grass, group 18 at
10 ppm; and Herb and spice, group 19 at 10 ppm.  Rohm and Haas Company
requested these tolerances under the Federal Food, Drug and Cosmetic
Act, as amended by the Food Quality Protection Act of 1996.  A Notice of
Filing was submitted and published in the Federal Register of March 19,
2001 (66 FR 15443) (FRL 6766-7).  Based on the data submitted by Rohm
and Haas Company, the Agency determined that only time-limited
tolerances for these residues could be established.  The Final Rule was
published on September 20, 2002 (67 FR 59193) (FRL-7198-5) with
time-limited tolerances expiring on September 30, 2007.  To enable
establishment of permanent tolerances, 24 additional rotational crop
trials were requested.  The data were submitted to the Agency on March 3
and June 17, 2003.  An extension of the tolerances which expired
September 30, 2007 is needed to allow for Agency review of the
additional rotational crop data.]  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 were 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. [Twenty-four rotation crops residue trials
were conducted and residues of methoxyfenozide and its metabolites
measured.  The requested tolerances are adequately supported. The
requested tolerances are adequately supported.]

B. Toxicological Profile  [The toxicological profile and endpoints for
methoxyfenozide which supports this petition to reestablish time-limited
tolerances were previously published in the Federal Register of August
31, 2005 (70 FRL-7732-3]

	1. Acute toxicity.  [as per Federal Register of August 31, 2005 (70
FRL-7732-3]

	2. Genotoxicty. [as per Federal Register of August 31, 2005 (70
FRL-7732-3]

	3. Reproductive and developmental toxicity. [NA-Remove as per Federal 

                Register of August 31, 2005 (70 FRL-7732-3]

	4. Subchronic toxicity. [as per Federal Register of August 31, 2005 (70
FRL-

                 7732-3]

	5. Chronic toxicity. [as per Federal Register of August 31, 2005 (70
FRL-7732-

                 3]

 

	6. Animal metabolism. [as per Federal Register of August 31, 2005 (70
FRL-

                7732-3] 

	7. Metabolite toxicology. [as per Federal Register of August 31, 2005
(70 FRL-

                7732-3] 

 

	8. Endocrine disruption. [as per Federal Register of August 31, 2005
(70 FRL-

                7732-3] 

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, proposed IR-4 minor uses and the
proposed time-limited tolerances for rotational crops.  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 studying 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. 2.16,
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.

The tolerances proposed involve crops commonly used as feed for
livestock: non-grass animal feed crops, such as alfalfa and clover. 
Therefore, an estimated animal dietary burden was conducted, in order to
confirm that these uses will not trigger residue levels above the
current tolerances on meat and poultry food commodities.  The
methodology used by Dow AgroSciences followed EPA’s OPPTS 860.1000
guidelines for residue chemistry test guidelines (ref.  ).

The maximum dietary burden in dairy and beef cattle estimated from all
existing and proposed uses on field feed crops (120 ppm on dairy and 111
ppm on beef cattle) was compared with the doses tested in the feeding
study conducted by Rohm and Haas with methoxyfenozide on dairy cattle
(TR-34-98-95) and submitted previously to the agency (ref  ).  All
calculated residues levels in muscle, fat, liver, kidney and milk were
found to be below the current tolerances for all meat commodities.

The maximum dietary burden in poultry estimated in an conservative
tier-I approach from all existing and proposed tolerances on field feed
crops (85 ppm) was compared with the highest tested dose in the feeding
study conducted by Rohm&Haas (23 ppm). Residue on poultry muscle, fat,
liver and eggs, were also calculated based on maximum intake from
current and proposed treated feed and findings of the feeding study
conducted by Rohm and Haas on laying hens (TR-34-00-33) and previously
submitted to the agency (ref.  ).

The maximum level of residues was estimated to be below the current
tolerances for all poultry commodities, with the exception of liver and
eggs. Considering the conservative assumptions used in this tier-1
assessment, it is likely that actual exposure in eggs resultant from
treated feed, will still comply with the current tolerance.

This tier-I assessment considers residues at tolerance levels for all
current and proposed uses; it also includes the worse-case adjustment
factors historically used in DEEM, when no refinements for processing
factors are available. 

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 Safety Factor (SF) = 1x for methoxyfenozide and therefore the cPAD
= 0.1 mg/kg/day.  The tier-I exposure for food was found to occupy up to
21.9% of the chronic population adjusted dose (PAD) for US-general
population and 52.4% of PAD for the most highly exposed population
subgroup, children 1 to 2 years old.  These results are 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.

All population subgroups have shown potential tier-I (worst-case)
exposure below the Agencies level of concern (100% cPAD).]

	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 (ref ).  The
Index Drinking Water Reservoir model (FIRST) was used to calculate
estimated the expected 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 is to
provide a coarse screen for assessing whether a pesticide is 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
and using the following default values for body weights and consumption:
2 liter (L)/70 kg (adult male), 2L/60 kg (adult female), and 1L/10 kg
(child).

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 can be 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 from the higher value of the two models, thus the output
from the screening model FIRST as an annual average concentration EEC =
15.8 parts per billion (ppb) was used.

The range of the calculated DWLOC varies from 480 ppb for the most
sensitive population subgroup (children 1-2 years old), to 2,700 ppb for
the U.S. general population.  Therefore, the lowest DWLOC is at least 30
times higher than the EEC estimated in drinking water by high screening
level models.

Dow AgroSciences thus concludes with reasonable certainty that residues
of methoxyfenozide in drinking water will not contribute significantly
to the aggregate chronic human health risk and that the chronic
aggregate exposure from methoxyfenozide residues in food and drinking
water will not exceed the Agency’s level of concern (100% of the
chronic PAD) for chronic dietary aggregate exposure by any population
subgroup.  EPA generally has no concern for exposures below 100% of the
chronic PAD, because it is a level at or below which daily aggregate
dietary exposure over a lifetime will not pose appreciable risks to the
health and safety of any population subgroup.  This risk assessment is
conservative in nature based on the assumptions used, and resultant in a
profile of methoxyfenozide that is very protective of human health.] 

	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 21.9% of the chronic PAD for the U.S. population.  If potable
water is aggregated into the tier-I dietary exposure, at the maximum
residue level estimated by EPA’s FIRST model, (0.016 ppm), the
aggregate exposure to the US-population is slightly increased to 22.3%
of the cPAD.  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.  Dow AgroSciences concludes
that there is 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 of the population sub-groups. 

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.  A complete toxicity
data base is available 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 above, Dow AgroSciences has concluded that chronic
dietary exposure to methoxyfenozide from the existing and proposed new
tolerances will utilize 43.5% of the cPAD for infants and children.  If
exposure from drinking water is aggregated to the tier-I dietary
exposure, at the maximum residue level estimated by EPA’s FIRST model,
(0.016 ppm), the aggregate exposure to children 1-6 is slightly
increased from 43.1 to 44.0% PAD, and the highest exposed subpopulation
is children 1-2 years at 52.9% of the cPAD.  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.  Despite the
potential for exposure to methoxyfenozide in drinking water, Dow
AgroSciences does not expect the aggregate exposure to exceed 100% of
the cPAD.  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 exposure to methoxyfenozide
residues. ]

F. International Tolerances

[There are several countries around the globe that have established
tolerances/ MRLs for methoxyfenozide. The most extensive list has been
published by Codex (25 food commodities). Among others countries,
Canada, Australia, Brazil, United Kingdom, and several other European
countries have MRL’s established for residues of methoxyfenozide.  By
comparing them, it is concluded that the MRLs established by different
agencies are not harmonized and are rather incompatible.  The
differences may be attributable to the use of diverse good agricultural
practices (GAPs) for efficacious pest control, different guidelines for
conducting field crop residue studies, and different calculation methods
used to propose tolerances.  Based on the current non-harmonized MRL
situation, it is not reasonable to conclude that the U.S. tolerance
levels can be harmonized with MRLs from other countries, and therefore
the condition of MRL incompatibility amongst differing countries,
relative to methoxyfenozide, will persist. ]

	

 	US-EPA OPPTS 860.1000 Background Residue Chemistry Test Guidelines,
part 9 (m) RawAgricultural and Processed Commodities in Livestock Feeds
Derived from Field Crops, as published at  

 	Bender, D., 1998c. Rohm and Haas report No. 34-98-95, Feeding Study
for RH-2485 in Lactating Cows.

 	Bender, D., 2000c; Rohm and Haas report no. 34-00-33, Feeding Study
for RH-2485 in Laying Hens. 

 	EPA Water Models as published on EFED’s web page at   HYPERLINK
"http://www.epa.gov/oppefed1/models/water" 
http://www.epa.gov/oppefed1/models/water , as of May 15, 2006.