Document ID: EPA-HQ-OPP-2007-0495-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-10-24T04:00Z

COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE  (10/31/2006)

EPA Registration Division contact: [Barbara Madden- 7505C 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]

[Insert petition number]

	EPA has received a pesticide petition ([insert petition number]) 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. by establishing a tolerance for residues of

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

	[methoxyfenozide, Intrepid 2F] in or on the raw agricultural commodity
[animal feed, non-grass, group 18, forage] at [35] parts per million
(ppm), [animal feed, non-grass, group 18, hay] at [85] parts per million
(ppm), [Poultry-liver] at [0.2] parts per million (ppm),[Eggs] at [0.04]
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 and was
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.  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
alfalfa and clover, as representative crops of subgroup 18:  non-grass
animal feed crops, has been submitted by Dow AgroSciences .  The
requested tolerances are adequately supported.]

B. Toxicological Profile  [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.  [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
new tolerances proposed in this tolerance petition.  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 assessment was conducted to evaluate potential risks due to
chronic dietary exposure of the U.S. population and selected population
subgroups to residues of methoxyfenozide.  This analysis cover all
registered crops, uses pending with the EPA, active and proposed Section
18, IR-4 minor crops uses and new proposed uses on non-grass animal feed
crops.  

The Dietary Exposure Evaluation Model™ (DEEM-FCID, version 2.03,
Exponent, Inc., Washington, DC-20036) was the model used for conducting
a 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 Raw Agricultural Commodities (RACs), as indicated by EPA/USDA FCID
recipe set as of August, 2002.  Dow AgroSciences assumed in a tier-I
analysis that 100% of crops would be treated and will contain
methoxyfenozide residues at the tolerance level. 

The dietary exposure analysis was based on Intrepid® current and
proposed labels, assuming the worst case use patterns, summarized in
Section B – Amount, Frequency and Time of Application of
Methoxyfenozide, of the present NOF.  

The currently proposed uses involve crops commonly used as feed for
livestock: non-grass animal feed crops, such are alfalfa and clover. 
Therefore, an estimated animal dietary burden was conducted, in order to
confirm that the newly proposed 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.  ).  A summary of
the estimated dietary intake for beef and dairy cattle, and also for
poultry, is presented in Table 3. 

The maximum dietary burden in dairy and beef cattle estimated from all
existing and proposed used 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  ).  Residues
were calculated in milk (cream and skim), muscle, fat, liver and kidney
of dairy cattle by extrapolating residues on dairy cattle from the next
higher dose tested at 183 ppm.  All residue levels in muscle, fat,
liver, kidney and milk were found to be below the current tolerances for
all meat commodities.  A summary of the residue estimated by this
assessment in meat, fat, kidney and milk of dairy and beef cattle is
presented in Table 4.

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.  ).  A summary of the maximum expected
residue in muscle, fat, liver and eggs is presented in Table 5.

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.  However,
based on the findings of this assessment the current tolerance on
poultry liver is requested to be increased from 0.1 to 0.2 ppm, and
current tolerance on eggs to be increased from 0.02 to 0.04 ppm. 

The actual dietary food exposure was calculated by the DEEM 2.03 model. 
This tier-I assessment considers residues at tolerance levels for all
current and proposed uses. 

Consumption patterns include results from CSFII 1994 and 1998 for
US-general population and subgroups by age groups from infants to
elderly.  The chronic tox-endpoint was the chronic reference dose (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) is 1x for
methoxyfenozide and therefore the cPAD = 0.1 mg/kg/day.  The tier-I
exposure was found to occupy up to 24.9% of the chronic population
adjusted dose (cPAD) for US-general population and 43.1% of cPAD for the
most highly exposed population subgroup, children 1 to 6 years old. 
These results should be viewed as conservative (health protective) risk
estimates due to the conservative nature of the assumptions used in the
tier I assessment.  Refinements such as use of percent crop-treated
information and/or anticipated residue values would yield lower
estimates of chronic dietary exposure. A summary of the findings of the
tier-I dietary risk assessment is presented in Table 6. 

All population subgroups have shown potential tier-I (worst-case)
exposure below the Agencies level of concern (100% cPAD).  Table 6 lists
the subgroups that are the most representative and/or sensitive.  They
are:  1. U.S. population (total);2. Infants and children;3. the most
sensitive of the females sub-groups, Females 13+(nursing); 4. the most
highly exposed of the remaining subgroups, in this case
Non-Hispanic/non-white/non-black]

	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 at
this stage 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).  

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. 
Modeling was conducted based on the environmental profile and the
maximum seasonal application rate proposed across current and proposed
labels for Intrepid®: 0.25 lb ai/acre, for maximum 4 applications per
season, with at least 7 days interval between applications.  FIRST was
used to generate the surface water EECs, because it is commonly used for
tier-I risk assessments.

The EECs estimated in ground-water by SCI-GROW 2.3 for chronic exposure
is 2.2 parts per billion (ppb). A summary report as produced by the
SCI-GROW 2.3 model is included in Table 7.

The concentration for chronic exposure from surface-water was estimated
by the screening model FIRST using an EEC of 15.8 parts per billion
(ppb). The FIRST model is used to estimate an annual average
concentration in surface water.  A summary report as produced by FIRST
is presented in Table 8. 

The DWLOCs for assessing chronic aggregate dietary risk can be
back-calculated by subtracting from the cRfD the amount of the estimated
dietary exposure.  A summary of the DWLOC calculated for different
sub-population groups is presented in Table 9. 

The range of the calculated DWLOC varies from 570 ppb for the most
sensitive population subgroup (children 1-6 years old), to 2,630 ppb for
the U.S. general population (48 contiguous states - all seasons). 
Therefore, the lowest DWLOC is at least 35 times higher than the EEC
estimated in drinking water by high screening level models.

The SCI-GROW and FIRST chronic EECs are much lower than the Agency’s
level of comparison (the DWLOC value for each population subgroup) for
methoxyfenozide residues in drinking water as a contribution to chronic
aggregate exposure.  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 considered to be a high confidence level, 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
doesn’t 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 24.9% 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 from 24.9
to 25.3% 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 in this report, Dow AgroSciences has concluded
that chronic dietary exposure to methoxyfenozide from the existing and
proposed new tolerances will utilize 43.1% 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 43.6 % 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.  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.  A
summary of the comparative MRLs from leading countries which establish
local MRLs is presented in Table 10. 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 originated by diverse good agricultural practices (GAPs) used 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 with
MRLs from other countries, and therefore the condition of MRL
incompatibility amongst differing countries, relative to
methoxyfenozide, will persist. ]

	

	

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part 9 (m) RawAgricultural and Processed Commodities in Livestock Feeds
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 	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.