Methoxyfenozide; Benzoic Acid, 3-methoxy-2-methyl-2-(3,5-
dimethylbenzoyl)-2-(1,1-dimethylethyl)hydrazide; Pesticide Tolerance
[Federal Register: July 5, 2000 (Volume 65, Number 129)]
[Rules and Regulations]
[Page 41355-41365]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr05jy00-14]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300983; FRL-6496-5]
RIN 2070-AB78
Methoxyfenozide; Benzoic Acid, 3-methoxy-2-methyl-2-(3,5-
dimethylbenzoyl)-2-(1,1-dimethylethyl)hydrazide; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: . This regulation establishes tolerances for residues of
methoxyfenozide in or on cotton, undelinted seed; cotton gin
byproducts; pome fruit; apple pomace, wet; milk, meat of cattle, goats,
hogs, horses and sheep and fat of cattle, goats, hogs, horses and
sheep; and tolerances for the combined residues of methoxyfenozide and
its glucuronide metabolite in meat byproduct (except liver) and liver
of cattle, goats, hogs, horses and sheep. Rohm and Haas Company
requested these tolerances under the Federal Food, Drug, and Cosmetic
Act (FFDCA), as amended by the Food Quality Protection Act (FQPA) of
1996.
DATES: This regulation is effective July 5, 2000. Objections and
requests for hearings, identified by docket control number OPP-300983,
must be received by EPA on or before September 5, 2000.
ADDRESSES: Written objections and hearing requests may be submitted by
mail, in person, or by courier. Please follow the detailed instructions
for each method as provided in Unit VI. of the SUPPLEMENTARY
INFORMATION. To ensure proper receipt by EPA, your objections and
hearing requests must identify
[[Page 41356]]
docket control number OPP-300983 in the subject line on the first page
of your response.
FOR FURTHER INFORMATION CONTACT: By mail: Joseph Tavano, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave.,
NW.,Washington, DC 20460; telephone number: (703) 305-6411; and e-mail
address: tavanojoseph@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be affected by this action if you are an agricultural
producer, food manufacturer, or pesticide manufacturer. Potentially
affected categories and entities may include, but are not limited to:
------------------------------------------------------------------------
Examples of
Categories NAICS codes potentially
affected entities
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Industry 111 Crop production
112 Animal production
311 Food manufacturing
32532 Pesticide
manufacturing
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This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in the table could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether or not this action might apply to certain entities. If you have
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.
B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?
1. Electronically. You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select ``Laws and
Regulations'' and then look up the entry for this document under the
``Federal Register--Environmental Documents.'' You can also go directly
to the Federal Register listings at http://www.epa.gov/fedrgstr/.
2. In person. The Agency has established an official record for
this action under docket control number OPP-300983. The official record
consists of the documents specifically referenced in this action, and
other information related to this action, including any information
claimed as Confidential Business Information (CBI). This official
record includes the documents that are physically located in the
docket, as well as the documents that are referenced in those
documents. The public version of the official record does not include
any information claimed as CBI. The public version of the official
record, which includes printed, paper versions of any electronic
comments submitted during an applicable comment period is available for
inspection in the Public Information and Records Integrity Branch
(PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy.,
Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The PIRIB telephone number is (703) 305-5805.
II. Background and Statutory Findings
In the Federal Register of (October 6, 1998, 63 FR 53656) (FRL-
6033-8), EPA issued a notice pursuant to section 408 of the FFDCA, 21
U.S.C. 346a as amended by the FQPA of 1996 (Public Law 104-170)
announcing the filing of a pesticide petition for tolerance by Rohm and
Haas Company, 100 Independence Mall West, Philadelphia, PA 19106-2399.
This notice included a summary of the petition prepared by Rohm and
Haas Company, the registrant. There were no comments received in
response to the notice of filing.
The petition requested that 40 CFR part 180 be amended by
establishing tolerances for residues of the insecticide,
methoxyfenozide, in or on cottonseed; cotton gin trash; pome fruit;
meat, kidney, meat byproducts and milk of cattle, goats, sheep and hogs
and fat of cattle, goats, sheep and hogs at 2.0, 25.0, 1.25, 0.02, 0.1
parts per million (ppm) respectively and tolerances for the combined
residues of methoxyfenozide and its glucuronide metabolite in or on
liver of cattle, goats, sheep, and hogs at 0.1 ppm.
Methoxyfenozide is a reduced risk pesticide which will be sold
under the trade name of Intrepid 2F. Methoxyfenozide controls codling
moth, green fruitworm, lesser appleworm, Oriental fruit moth,
obliquebanded leafroler, eyespotted bud moth, fruittree leafroller,
pandemis leafroller, redbanded leafroller, variegated leafroller,
tufted apple bud moth, spotted tentiform leafminer and Western
tentiform leafminer on pome fruit and cotton bollworm, tobacco budworm,
beet armyworm, cabbage looper, cotton leafworm, fall armyworm, Southern
armyworm, soybean looper and true armyworm on cotton.
Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is ``safe.'' Section
408(b)(2)(A)(ii) defines ``safe'' to mean that ``there is a reasonable
certainty that no harm will result from aggregate exposure to the
pesticide chemical residue, including all anticipated dietary exposures
and all other exposures for which there is reliable information.'' This
includes exposure through drinking water and in residential settings,
but does not include occupational exposure. Section 408(b)(2)(C)
requires EPA to give special consideration to exposure of infants and
children to the pesticide chemical residue in establishing a tolerance
and to ``ensure that there is a reasonable certainty that no harm will
result to infants and children from aggregate exposure to the pesticide
chemical residue.''
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. For further discussion of the
regulatory requirements of section 408 and a complete description of
the risk assessment process, see the final rule on Bifenthrin Pesticide
Tolerances November 26, 1997 (62 FR 62961) (FRL-5754-7).
III. Aggregate Risk Assessment and Determination of Safety
Consistent with section 408(b)(2)(D), EPA has reviewed the
available scientific data and other relevant information in support of
this action. EPA has sufficient data to assess the hazards of and to
make a determination on aggregate exposure, consistent with section
408(b)(2), for a tolerance for residues of methoxyfenozide on cotton,
undelinted seed; cotton gin byproducts; pome fruit; apple pomace, wet;
milk; meat of cattle, goats, hogs, horses, and sheep and fat of cattle,
goats, hogs, horses, and sheep at 2.0, 35.0, 1.5, 7.0, 0.02, 0.02, 0.1
ppm respectively, and tolerances for the combined residues of
methoxyfenozide and its glucuronide metabolite in liver of cattle,
goats, hogs, horses and sheep and meat byproducts (except liver) of
cattle, goats, hogs, horses and sheep at 0.1 and 0.02 ppm respectively.
EPA's assessment of the
[[Page 41357]]
dietary exposures and risks associated with establishing the tolerance
follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. The nature of the toxic effects caused by methoxyfenozide are
discussed in this unit.
Acute toxicity studies with technical grade: Oral LD50
in the rat is > 5,000 milligrams/kilograms (mg/kg) for males and
females-Toxicity Category IV; Oral LD50 in the mouse is >
5,000 mg/kg for males and females-Toxicity Category IV; Dermal
LD50 in the rat is > 2,000 mg/kg-Toxicity Category III;
Inhalation LC50 in the rat is > 4.3 millgram/liter (mg/L)-
Toxicity Category IV; Primary Eye Irritation in the rabbit -very mild
irritant-Toxicity Category IV; Primary skin irritation in the rabbit-
not a skin irritant-Toxicity Category IV. Methoxyfenozide is not a skin
sensitizer.
In an acute neurotoxicity study in rats, statistically significant
decreased hindlimb grip strength was observed in male rats at 3 hours
(approximate time of peak effect) following a single oral dose of 2,000
mg/kg (limit dose) of methoxyfenozide. Decreased hindlimb grip strength
was also observed in the male rats at 7 and 14 days, but was not
statistically significant. No other systemic or neurotoxic effects were
observed in the male rats or in the female rats at any time in this
study. Since this marginal effect occurred only in one sex, was
statistically significant at only one time, was observed only at the
high dose (limit dose) and no other signs of toxicity were observed in
the rats in this study, this possible effect is not considered to be
biologically significant. In addition, neither decreased hindlimb grip
strength nor any other signs of neurotoxicity were observed in any of
the animals at any time in a 90-day subchronic neurotoxicity study in
rats.
In a 2-week range-finding dietary study in rats, treatment-related
effects were observed at > 5,000 ppm in the liver (increased liver
weights and hepatocellular hypertrophy in males and females), in the
thyroid gland (hypertrophy/hyperplasia of follicular cells in males and
females), and in the adrenal gland (increased adrenal weights and/or
hypertrophy of the zona fasciculata in females). Hypertrophy/
hyperplasia of thyroid follicular cells was also observed in males and
females at 1,000 ppm, the lowest observed adverse effect level (LOAEL)
in this study. The no observed adverse effect level (NOAEL) was 250
ppm. Treatment-related hematological changes were not observed in the
rats in this study.
In a 3-month feeding study in rats, the predominant treatment-
related effects were increased liver weights in males and females and
periportal hepatocellular hypertrophy in all males and females at
20,000 ppm highest dose tested (HDT) and at 5,000 ppm. In addition, at
20,000 ppm, a slightly decreased (7-8%) RBC count and slightly
decreased (7-8%) hemoglobin concentration, compared to control rats,
were observed in the females. The LOAEL in this study was 5,000 ppm
(353/379 mg/kg/day in males/females, respectively). The NOAEL was 1,000
ppm (69/72 mg/kg/day in males/females, respectively). Although observed
in the 2-week dietary study and in the 2-year chronic feeding/
carcinogenicity study in rats, treatment-related effects in the thyroid
and adrenal glands were not observed in the rats in this 3-month study.
There is no available biological explanation for this difference in
findings in the studies.
In a 2-year combined chronic feeding/carcinogenicity study in rats,
the following treatment-related effects were observed at 20,000 ppm
(highest dose tested): decreased survival in males, decreased body
weight and food efficiency in females during the last year of the
study, hematological changes (decreased RBC counts, hemoglobin
concentrations, and/or hematocrits; methemoglobinemia; and increased
platelet counts) in males and females, increased liver weights and
periportal hepatocellular hypertrophy in males and females, thyroid
follicular cell hypertrophy in males, altered thyroid colloid in males
and females, and increased adrenal weights in males and females. At
8,000 ppm, the following treatment-related effects were observed:
hematological changes (decreased RBC counts, hemoglobin concentrations,
and/or hematocrits in males and females), liver toxicity (increased
liver weights in males and periportal hepatocellular hypertrophy in
males and females), histopathological changes in the thyroid (increased
follicular cell hypertrophy in males and altered colloid in males) and
possible adrenal toxicity (increased adrenal weights in males and
females). The LOAEL in this study was 8,000 ppm (411/491 mg/kg/day in
males/females, respectively), based on the effects described above. The
NOAEL was 200 ppm (10.2/11.9 mg/kg/day in males/females, respectively).
This NOAEL was used to establish the reference dose (RfD) for
methoxyfenozide. Utilizing an uncertainty factor of 100 to account for
both interspecies extrapolation (10x) and intraspecies variability
(10x), the chronic RfD for methoxyfenozide was calculated to be 0.10
mg/kg/day. No evidence of carcinogenicity was observed in this study.
Dosing was considered adequate because of the decreased survival in
males and the decreased body weights and food efficiency in females at
20,000 ppm. In addition, the HDT for both males and females, 20,000 ppm
(1,045/1,248 mg/kg/day in males/females, respectively), is higher than
the limit dose of 1,000 mg/kg/day.
In a 2-week range-finding study in dogs, treatment-related
hematological changes were observed in both males and females at 3,500
ppm, 7,000 ppm, 15,000 ppm, and 30,000 ppm (HDT). These changes
included decreased RBC counts, decreased hemoglobin concentrations,
decreased hematocrits, decreased MCHC, increased MCV, increased MCH,
increased Heinz bodies, methemoglobinemia, changes in RBC morphology
such as Howell-Jolly bodies and polychromasia, increased reticulocyte
counts, increased nucleated RBC and increased platelet counts. At the
same dose levels (> 3,500 ppm), increased spleen weights and/or
enlarged spleens were also observed. At 7,000 ppm, plasma total
bilirubin was increased. The LOAEL in this study was 3,500 ppm (90-184
mg/kg/day in males and females). The NOAEL was 300 ppm (11-16 mg/kg/day
in males and females).
In a 3-month feeding study in dogs, no treatment-related effects
other than a suggestion of decreased body weight gains in males and
females were observed in either males or females at the HDT viz. 5,000
ppm (198/209 mg/kg/day in males/females, respectively). Although
hematological effects were noted in dogs in the 2-week range-finding
study at > 3,500 ppm (90-184 mg/kg/day) and in the 1-year chronic
feeding study at > 3,000 ppm (106/111 mg/kg/day), hematological changes
were not observed in this 3-month study at 5,000 ppm (198/209 mg/kg/
day). There is no available biological explanation for this difference
in findings in the studies.
As part of the 3-month study in dogs, some male and female dogs
were given 15 ppm (0.6 mg/kg/day) of methoxyfenozide in the diet for 15
weeks followed by an increase in the dietary dose to 15,000 ppm (422/
460 mg/kg/day in males/females,
[[Page 41358]]
respectively) for an additional 6 weeks. After about 2 weeks and 6
weeks at 15,000 ppm, hematological examinations were conducted. No
hematological changes in these dogs were observed. Apparently,
pretreatment of the dogs at 15 ppm for 15 weeks prevented the
occurrence of hematological changes which would have been expected to
occur based on results in the 2-week and 1-year feeding studies. One
possible explanation is that the liver microsomal enzyme system may
have been stimulated so much during pretreatment at 15 ppm that the
metabolic (detoxification) rate of methoxyfenozide was increased to the
point where blood levels of methoxyfenozide may have remained below
critical effect levels at 15,000 ppm. Another possible explanation is
that compensatory mechanisms for replacing damaged RBC in pretreated
dogs may have been so efficient that hematological changes were not
observed in these dogs even at 15,000 ppm. Other explanations for this
finding are also possible.
In a 1-year chronic feeding study in dogs, the predominant toxic
effects were anemia and signs of an associated compensatory response.
At 30,000 ppm, the HDT, the following treatment-related effects were
observed in both males and females: decreased RBC counts, decreased
hemoglobin concentrations, decreased hematocrits, methemoglobinemia,
nucleated RBC, increased platelets, increased serum total bilirubin,
bilirubinurea, increased hemosiderin in macrophages in liver and
spleen, and increased hyperplasia in bone marrow of rib and sternum.
Increased liver weights in males and females and increased thyroid
weights in males were also observed at 30,000 ppm. Signs of anemia were
also noted at 3,000 ppm and included decreased RBC counts, decreased
hemoglobin concentrations, decreased hematocrits, methemoglobinemia,
increased platelets, and increased serum total bilirubin and
bilirubinurea. The LOAEL in this study was 3,000 ppm (106/111 mg/kg/day
in males/females, respectively). The NOAEL was 300 ppm (9.8/12.6 mg/kg/
day in males/females, respectively).
In a 3-month feeding study in mice, the only treatment-related
effect was decreased body weight gain in males and females at 7,000
ppm, the HDT. The LOAEL in this study was 7,000 ppm (1,149/1,742 mg/kg/
day in males/females, respectively) and the NOAEL was 2,500 ppm (428/
589 mg/kg/day in males/females, respectively). In an 18-month
carcinogenicity study in mice (MRID 44617729), no treatment-related
effects were observed at doses up to and including the limit dose of
7,000 ppm (1,020/1,354 mg/kg/day in males/females, respectively). No
evidence of carcinogenicity was observed in this study. Dosing was
considered adequate because the HDT for both males and females, 7,000
ppm (1,020/1,354 mg/kg/day in males/females, respectively), is higher
than the limit dose of 1,000 mg/kg/day.
In a battery of four mutagenicity studies (with and without
metabolic activation, as appropriate for the specific study), technical
grade methoxyfenozide was negative for genotoxicity in all four
studies. The four studies satisfy the new revised mutagenicity
guideline requirements for a new chemical (published in 1991). An
additional mutagenicity study, performed on RH-117,236 (Metabolite M-
B), a metabolite of methoxyfenozide, was also negative for
genotoxicity.
Based on the lack of evidence of carcinogenicity in male and female
rats as well as in male and female mice and on the lack of genotoxicity
in an acceptable battery of mutagenicity studies, methoxyfenozide is
classified as a ``not likely'' human carcinogen according to the EPA.
In a developmental toxicity study in rats, no signs of maternal
toxicity in dams or of developmental toxicity in fetuses were observed
at the limit dose of 1,000 mg/kg/day. The NOAEL in this study for both
maternal toxicity and developmental toxicity was 1,000 mg/kg/day. The
LOAEL was > 1,000 mg/kg/day. Similarly, in a developmental toxicity
study in rabbits, no signs of maternal toxicity or of developmental
toxicity were observed at the limit dose of 1,000 mg/kg/day. The NOAEL
in this study for both maternal toxicity and developmental toxicity was
1,000 mg/kg/day. The LOAEL was > 1,000 mg/kg/day.
In neither the developmental toxicity study in rats nor in the
developmental toxicity study in rabbits was there any evidence for
increased susceptibility of fetuses to in utero exposure to
methoxyfenozide. In these studies, methoxyfenozide was determined not
to be a developmental toxicant.
In a 2-generation (1 litter/generation) reproduction study in rats,
treatment-related parental toxicity was observed only at 20,000 ppm,
the HDT. At this dose, increased liver weights were observed in males
and females of both generations and midzonal to periportal
hepatocellular hypertrophy was observed in the livers of all males and
females of both generations. The LOAEL for parental toxicity was 20,000
ppm (1,552/1,821 mg/kg/day for males/females, respectively) and the
NOAEL was 2,000 ppm (153/181 mg/kg/day for males/females,
respectively). There were no treatment-related effects on reproductive
parameters for adult (parent) animals. The NOAEL for reproductive
toxicity was 20,000 ppm. Since no treatment-related effects were
observed in the pups, the NOAEL for neonatal toxicity was also, 20,000
ppm. The NOAEL for parental toxicity in this reproduction study is
higher than the NOAEL for the 2-year combined chronic feeding/
carcinogenicity study in rats because many of the toxic effects
observed in the 2-year study at the LOAEL (hematological changes, liver
toxicity, histopathological changes in the thyroid gland and increased
adrenal weights) were not examined in the reproduction study.
In a metabolism study in rats, 14C-methoxyfenozide was
rapidly absorbed, distributed, metabolized and almost completely
excreted within 48 hours. The major route of excretion was feces (86-
97%) with lesser amounts in the urine (5-13%). An enterohepatic
circulation was observed. The test material was metabolized principally
by O-demethylation of the A-ring methoxy group and oxidative
hydroxylation of the B-ring methyl groups followed by conjugation with
glucuronic acid. No significant sex-related or dose-dependent
differences in metabolic disposition were noted. Seven metabolites and
the parent accounted for 74-90% of the administered dose in all groups.
The glucuronide conjugates are considered to be less toxic than the
parent compound because glucuronide conjugation is well known to be a
commonly occurring ``detoxification'' mechanism in mammalian species
since it results in the formation of more polar, more water-soluble
metabolites which are readily and easily excreted from the body (in
this case, in the bile and urine). Further, based on similarities of
chemical structure, the non-conjugated metabolites would be expected to
be no more toxic than the parent compound. In a dermal absorption study
in rats using an 80% wettable powder formulation as the test material,
the cumulative dermal absorption of test material after a 10- or 24-
hour dermal exposure was determined to be 2%. In a 28-day dermal
toxicity study in rats, no treatment-related systemic or skin effects
were observed at the limit dose of 1,000 mg/kg/day (HDT). Regarding
effects on endocrine organs, methoxyfenozide affected the thyroid gland
and adrenal gland in the 2-week and 2-year feeding studies in rats. In
the thyroid gland, hypertrophy/hyperplasia
[[Page 41359]]
of follicular cells and altered colloid were observed in males and
females at or near the LOAEL in both of these studies. In the adrenal
gland, increased adrenal weights and hypertrophy of the zona
fasciculata were also observed in males and females at or near the
LOAEL. In addition, in the 1-year chronic feeding study in dogs,
increased thyroid weight in males was observed, but only at the very
high dose of 30,000 ppm. Since the definition and regulatory
significance of the term ``endocrine disruptor chemical'' has not yet
been established by the Agency, it is not clear whether
methoxyfenozide, on the basis of these effects on the thyroid gland and
adrenal gland, should be considered to be an ``endocrine disruptor
chemical.'' Other than the morphological changes described above, there
were no signs of thyroid or adrenal dysfunction in these or in any
other studies on methoxyfenozide.
B. Toxicological Endpoints
1. Acute toxicity. 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. In the acute neurotoxicity
study in rats, statistically significant decreased hindlimb grip
strength was observed in male rats at 3 hours (approximate time of peak
effect) following a single oral dose of 2,000 mg/kg (limit dose) of
methoxyfenozide. Decreased hindlimb grip strength was also observed in
the male rats at 2,000 mg/kg at 7 and 14 days, but was not
statistically significant. Decreased hindlimb grip strength was not
observed in the male rats at 1,000 mg/kg. No other systemic or
neurotoxic effects were observed in the male rats or in the female rats
at any time in the study. Since this marginal effect occurred only in
one sex, was statistically significant only one time, was observed only
at the high dose (limit dose) and no other signs of toxicity were
observed in the rats in the study, this equivocal effect is not
considered to be an appropriate toxicological endpoint for acute
dietary risk assessments. In addition, decreased hindlimb grip strength
was not observed in a subchronic neurotoxicity study in rats in any of
the animals at any time. It is also noted that the acute oral
LD50 for male and female rats for technical grade
methoxyfenozide (98% active ingredient (a.i.) is > 5,000 mg/kg
(Toxicity Category IV). No treatment-related effects were observed in
either dams or pups in the developmental toxicity studies in rats or
rabbits at doses up to the limit dose of 1,000 mg/kg/day. Thus the risk
from acute exposure is considered negligible.
2. Short- and intermediate-term toxicity. In a 28-day repeated dose
dermal toxicity study in rats, no systemic or dermal toxicity was
observed at 1,000 mg/kg/day, the HDT (limit dose). By applying the
dermal absorption factor of 2% (derived from a dermal absorption study
in rats, to the NOAEL of 10.2 mg/kg/day and the LOAEL of 411 mg/kg/day
in the 2-year combined chronic feeding/carcinogenicity study in rats,
the oral NOAEL and LOAEL in this study are equivalent to a dermal NOAEL
of 510 mg/kg/day and a dermal LOAEL of 20,550 mg/kg/day. By applying
the dermal absorption factor of 2% to the NOAEL of 9.8 mg/kg/day and
the LOAEL of 106.1 mg/kg/day in the 1-year chronic feeding study in
dogs, the oral NOAEL and LOAEL in this study are equivalent to a dermal
NOAEL of 490 mg/kg/day and a dermal LOAEL of 5,305 mg/kg/day. The
likelihood of toxic effects resulting from repeated dermal exposure to
methoxyfenozide is quite low. Further, based on the use pattern, no
long-term dermal exposure is expected to occur.
Methoxyfenozide is a non-volatile solid with a very low vapor
pressure of > 1 x 10-7 torr (or > 1.33 x 10-5
pascal). In an acute inhalation toxicity study in rats, the acute
inhalation LC50 for technical grade methoxyfenozide dust
(98% a.i.) was determined to be > 4.3 mg/L (> 2x limit dose, Toxicity
Category IV) for both male and female rats. In another acute inhalation
toxicity study in rats), the acute inhalation LC50 for RH-
112,485 80WP formulation 80% a.i. was determined to be > 4.5 mg/L (> 2x
limit dose, Toxicity Category IV) for both male and female rats. In
both of these acute inhalation toxicity studies, there were no
mortalities, treatment-related clinical signs, changes in body weights
or necropsy findings. Based on the low vapor pressure, the low acute
inhalation toxicity (Toxicity Category IV) of the technical grade
product and the formulated product, the packaging of the formulated
product (water soluble pouches), the application rate (0.05 to 0.4 lb.
a.i./acre for a maximum of 2.0 lb. ai/season), and the application
method, there is minimal concern for potential inhalation risk.
Further, based on the use pattern, no long-term inhalation exposure is
expected to occur.
3. Chronic toxicity. EPA has established the RfD for
methoxyfenozide at 0.10 mg/kg/day. This RfD is based on a NOAEL of 10.2
mg/kg/day and an UF of 100 accounting for both interspecies
extrapolation (10x) and intraspecies variability (10x). This chronic
RfD is based on the 2-year combined chronic feeding/carcinogenicity
study in rats, in which the following effects were observed at the
LOAEL of 411/491 mg/kg/day in males/females: hematological changes
(decreased RBC counts, hemoglobin concentrations, and/or hematocrit in
males and females), liver toxicity (increased liver weights in males
and periportal hepatocellular hypertrophy in males and females),
histopathological changes in the thyroid (increased follicular cell
hypertrophy and altered colloid in males) and possible adrenal toxicity
(increased adrenal weights in males and females). EPA determined that
the 10x Safety Facter for the protection of infants and children (as
required by FQPA) should be reduced to 1x. Therefore, the chronic
Population Adjusted Dose (cPAD) is the same as the RFD. This cPAD is
used in assessing chronic risk and applies to all population subgroups.
Reducing the 10x safety factor to 1x is supported by the following
factors:
i. The toxicology data base for methoxyfenozide is complete for
assessment of potential hazard to infants and children.
ii. Based on weight-of-the-evidence considerations, EPA determined
that a developmental neurotoxicity study in rats is not required to
support the registration of methoxyfenozide.
iii. In developmental toxicity studies in rats and rabbits, no
increased susceptibility in fetuses as compared to maternal animals was
observed following in utero exposures.
iv. In a 2-generation reproduction study in rats, no increased
susceptibility in pups as compared to adults was observed following in
utero and postnatal exposures.
v. The exposure assessments will not underestimate the potential
dietary (food and drinking water) or non-dietary exposures for infants
and children from the use of methoxyfenozide.
4. Carcinogenicity. Methoxyfenozide has been classified as a ``not
likely'' human carcinogen. This classification is based on the lack of
evidence of carcinogenicity in male and female rats as well as in male
and female mice and on the lack of genotoxicity in an acceptable
battery of mutagenicity studies.
C. Exposures and Risks
1. From food and feed uses. In today's action tolerances will be
established (40 CFR part 180) for the residues of methoxyfenozide on
cotton, undelinted seed; cotton gin byproducts; pome fruit; apple
pomace, wet; milk; meat of cattle,
[[Page 41360]]
goats, hogs, horses and sheep and fat of cattle, goats, hogs, horses
and sheep at 2.0, 35.0, 1.5, 7.0, 0.02, 0.02, 0.1 ppm and tolerances
for the combined residues of methoxyfenozide and its glucuronide
metabolite in liver of cattle, goats, hogs, horses and sheep and meat
byproducts (except liver) of cattle, goats, hogs, horses and sheep at
0.1 and 0.02 ppm respectively. Risk assessments were conducted by EPA
to assess dietary exposures from methoxyfenozide as follows.
i. Acute exposure and risk. Acute dietary risk assessments are
performed for a food-use pesticide if a toxicological study has
indicated the possibility of an effect of concern occurring as a result
of a 1-day or single exposure. 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. This risk is considered to be
negligible.
ii. Chronic exposure and risk. EPA used the Dietary Exposure
Evaluation Model (DEEM ) software 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 conducted in 1989-1992. EPA has made the assumptions that
100% of pome fruit and cotton would be treated and contain
methoxyfenozide residues at the tolerance level. The following
tolerance levels were used in the analysis:
------------------------------------------------------------------------
Tolerance Level (parts per
Commodity million) (ppm)
------------------------------------------------------------------------
Cotton, underlinted seed.................. 2.0 ppm
Pome fruits............................... 1.5 ppm
Milk...................................... 0.02 ppm
Meat*..................................... 0.02 ppm
Meat byproducts* (except liver)........... 0.02 ppm
Fat*...................................... 0.1 ppm
Liver..................................... 0.1 ppm
------------------------------------------------------------------------
*of cattle, goats, hogs, horses and sheep.
Processing factors were also applied to apple juice concentrate
(3x), dried apples (8x), dried beef (1.92x), dried pears (6.25x), and
dried veal (1.92x). The processing factors are default values from
DEEM.
As shown in the following table, the resulting dietary food
exposures occupy up to 11% of the Chronic PAD for the most highly
exposed population subgroup, non-nursing infants. 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 even lower estimates of chronic
dietary exposure.
Summary: Chronic Dietary Exposure Analysis by DEEM (Tier 1)
------------------------------------------------------------------------
Exposure (mg/kg/
Population Subgroup1 day) % of Chronic PAD2
------------------------------------------------------------------------
U.S. population (total)......... 0.001839 1.8
All infants (> 1 year).......... 0.009617 9.6
Nursing infants................. 0.005605 5.6
Non-nursing infants............. 0.011306 11
Children (1-6 years)............ 0.007350 6.8
Children (7-12 years)........... 0.003103 2.8
U.S. population (autumn season). 0.002285 2.3
U.S. population (winter season). 0.001891 1.9
Northeast region................ 0.002014 2.0
Western region.................. 0.002004 2.0
Non-hispanic whites............. 0.001917 1.9
Non-hispanic/non-white/non-black 0.002025 2.0
Females (> 13 years, nursing)... 0.002479 2.5
Pacific region.................. 0.002023 2.0
------------------------------------------------------------------------
1 The subgroups listed are: (1) The U.S. population (total); (2) those
for infants and children; (3) the other subgroup(s), if any, for which
the percentage of the Chronic PAD occupied is greater than that
occupied by the subgroup U.S. population (total); and, (4) the most
highly exposed of the females subgroups (in this case, females, > 13
years, nursing).
2 Percent chronic PAD = (Exposure Chronic PAD) x 100%.
2. From drinking water. The Agency currently lacks sufficient
water-related exposure data from monitoring to complete a quantitative
drinking water exposure analysis and risk assessment for
methoxyfenozide. Therefore, the Agency is presently relying on
computer-generated estimated environmental concentrations (EECs).
GENEEC and/or PRZM/EXAMS (both produce estimates of pesticide
concentration in a farm pond) are used to generate EECs for surface
water and SCI-GROW (an empirical model based upon actual monitoring
data collected for a number of pesticides that serve as benchmarks)
predicts EECs in ground water. 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 by
the Agency 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, GENEEC, PRZM/EXAMS).
i. Acute exposure and risk. Because no acute dietary endpoint was
determined, the Agency concludes that there is a reasonable certainty
of no harm from acute exposure from drinking water.
ii. Chronic exposure and risk. EPA conducted its Tier II screening-
level assessments using the simulation models SCI-GROW and PRZM/EXAMS
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 for methoxyfenozide (0.4 lb
ai/acre x 5 applications/acre/year on cotton). PRZM/EXAMS was used to
generate the surface water EECs, because it can factor the persistent
nature of the chemical into the estimates.
The EECs for assessing chronic aggregate dietary risk are 312 parts
per billion (ppb) (in ground water, based on SCI-GROW) and 3,197 ppb
(in surface water, based on the PRZM/EXAMS, long-term mean). The back-
calculated DWLOCs for assessing chronic aggregate dietary risk range
from 890 ppb for the most highly exposed population subgroup (Non-
nursing infants, > 1-year old) to 3,400 ppb for the U.S. population (48
contiguous States--all seasons) and the U.S. population (autumn
season).
The SCI-GROW and PRZM/EXAMS chronic EECs are less than the Agency's
[[Page 41361]]
level of comparison (the DWLOC value for each population subgroup) for
methoxyfenozide residues in drinking water as a contribution to chronic
aggregate exposure. EPA 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 cPAD) for chronic dietary aggregate exposure by any population
subgroup. EPA generally has no concern for exposures below 100% of the
cPAD, 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 high confidence, conservative, and very protective of human
health.
3. From 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.
4. Cumulative exposure to substances with a common mechanism of
toxicity. 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, EPA has not assumed that methoxyfenozide has a common
mechanism of toxicity with other substances. For information regarding
EPA's efforts to determine which chemicals have a common mechanism of
toxicity and to evaluate the cumulative effects of such chemicals, see
the final rule for Bifenthrin Pesticide Tolerances November 26, 1997
(62 FR 62961) (5754-7).
D. Aggregate Risks and Determination of Safety for U.S. Population
1. Acute risk. Since no acute toxicological endpoints were
established, EPA considers acute aggregate risk to be negligible.
2. Chronic risk. Using the DEEM exposure assumptions described in
this unit, EPA has concluded that aggregate exposure to methoxyfenozide
from food will utilize 1.8% of the cPAD for the U.S. population. The
major identifiable subgroup with the highest aggregate exposure is non-
nursing infants (> 1-year old) at 11% of the cPAD and is discussed
below. 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, EPA does not expect the aggregate
exposure to exceed 100% of the cPAD. EPA concludes that there is a
reasonable certainty that no harm will result from aggregate exposure
to methoxyfenozide residues.
3. Short- and intermediate-term risk. Short- and intermediate-term
aggregate exposure takes into account chronic dietary food and water
(considered to be a background exposure level) plus indoor and outdoor
residential exposure.
Since there are currently no registered indoor or outdoor
residential non-dietary uses of methoxyfenozide and no short or
intermediate term toxic endpoints, EPA considers short or intermediate
term aggregate risks to be negligible.
4. Aggregate cancer risk for U.S. population. Methoxyfenozide is
classified as a ``not likely'' human carcinogen. Therefore this risk
does is negligible.
5. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
from aggregate exposure to methoxyfenozide residues.
E. Aggregate Risks and Determination of Safety for Infants and Children
1. Safety factor for infants and children--In general. 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
tenfold margin of safety for infants and children in the case of
threshold effects to account for prenatal and postnatal toxicity and
the completeness of the data base 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 (usually 100 for combined
interspecies and intraspecies variability) and not the additional
tenfold MOE/UF when EPA has a complete data base under existing
guidelines and when the severity of the effect in infants or children
or the potency or unusual toxic properties of a compound do not raise
concerns regarding the adequacy of the standard MOE/safety factor.
2. Prenatal and postnatal sensitivity. The toxicology data base 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.
3. Conclusion. There is a complete toxicity data base for
methoxyfenozide and exposure data are complete or are estimated based
on data 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.
4. Acute risk. Since no acute toxicological endpoints were
established, EPA considers acute aggregate risk to be negligible.
5. Chronic risk. Using the exposure assumptions described in this
unit, EPA has concluded that aggregate exposure to methoxyfenozide from
food will utilize 11% of the cPAD for infants and children. 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
[[Page 41362]]
methoxyfenozide in drinking water, EPA does not expect the aggregate
exposure to exceed 100% of the cPAD.
6. Short- or intermediate-term risk. Short and intermediate term
risks are judged to be negligible due to the lack of significant
toxicological effects observed.
7. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to infants and children from aggregate exposure to methoxyfenozide
residues.
IV. Other Considerations
A. Metabolism in Plants and Animals
The qualitative nature of methoxyfenozide residues in plants is
adequately understood based upon acceptable cotton, apple and grape
metabolism studies. EPA has determined that the residue of concern for
dietary exposure and tolerance setting purposes in primary crops and
water is the parent compound, methoxyfenozide.
The qualitative nature of the residue in animals is adequately
understood based on acceptable studies conducted on goats and laying
hens. EPA has determined that the residue of concern in milk and
ruminant tissues (other than liver and kidney) is the parent compound,
methoxyfenozide. The residue of concern in ruminant liver and kidney is
the parent compound, methoxyfenozide, and its glucuronide metabolite
designated as RH-141,518 (also referred to as RH-1518). The glucuronide
metabolite was included in the tolerance expression for liver and
kidney because the conjugation may be reversible and it comprises a
significant portion of the total radioactive residues (TRR) (up to 42%
TRR in kidney and up to 29% TRR in liver) in those tissues.
B. Analytical Enforcement Methodology
The petitioner has proposed HPLC/UV Method TR 34-98-87 for the
enforcement of tolerances for pome fruits. Adequate confirmatory method
validation, radiovalidation, and independent method validation data
have been submitted for this method. This method was sent to the EPA
laboratory for a petition method validation (PMV). The laboratory has
reported that the pome fruit method (Method TR 34-98-87) is adequate in
the interim for enforcement of the proposed tolerances for
methoxyfenozide in/on pome fruit. Initial recoveries (60%) in the PMV
were just below the minium acceptable recovery level (70%) as specified
in OPPTS Harmonized Test Guidelines 860.1340. The laboratory modified
the method and achieved acceptable recoveries with the modified method.
EPA will require that Rohm and Haas Company revise and modify the
method. Additional recovery data will be required for the revised
method.
The petitioner has proposed Method TR 43-96-88 for the enforcement
of tolerances for cotton. This method is a shortened version of the
pome fruit method. Thus, EPA concludes that Method TR 34-96-87 is
adequate for enforcement of the proposed tolerances for residues of
methoxyfenozide in/on cotton commodities. The validation of the cotton
method is in progress. EPA expects that Method TR 43-96-88 will need to
be modified or revised and additional recovery data may be required.
EPA will require Rohm and Haas Company to revise and modify the cotton
method and submit any additional recovery data if necessary.
The petitioner has proposed Method TR 34-98-106 for the enforcement
of tolerances in animal commodities. This method determines residues of
methoxyfenozide (HPLC/UV) in fat, cream, milk, and muscle and residues
of methoxyfenozide and its glucuronide metabolite, RH-141,518 (HPLC/MS)
in liver and kidney. Adequate confirmatory method validation,
radiovalidation, and independent method validation data, have been
submitted for this method. This method has been forwarded to the EPA
laboratory for petition method validation (PMV). The method has passed
the PMV, however it requires some minor revisions. EPA will require
that Rohm and Haas Company revise the method and resubmit the final
revised method.
The petitioner submitted data concerning the recovery of residues
of methoxyfenozide using Food and Drug Administration (FDA)
multiresidue method protocols (PAM Vol. I). Methoxyfenozide was not
recoverable by these methods. These data will be forwarded to FDA for
evaluation.
EPA has determined that the residues of concern in ruminant liver
and kidney are methoxyfenozide and its metabolite RH-141,518. Data
concerning the recovery of residues of RH-141,518 using FDA
multiresidue method protocols (PAM Vol. I) will be required. This will
be made a condition of the registration for methoxyfenozide.
Adequate enforcement methodology is available to enforce the
tolerance expression. The methods may be requested from: Calvin Furlow,
PRRIB, IRSD (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460; telephone
number: (703) 305-5229; e-mail address: furlow.calvin@epa.gov.
C. Magnitude of Residues
1. Magnitude of the residue in apples and pears. An adequate number
of geographically representative field trials were submitted to support
the proposed use on pome fruits. Apples and pears are the
representative commodities of this crop group. These studies were
conducted via use patterns approximating those proposed by this
petition. Residues of methoxyfenozide ranged from 0.16 to 1.2 ppm in/on
apples and from 0.21 to 0.93 ppm in/on pears treated with the 80% WP
formulation according to the maximum proposed use patterns. The results
of the field trials indicate that residues of methoxyfenozide will not
exceed 1.5 ppm in/on pome fruit when treated as proposed. Rohm and Haas
Company proposed a tolerance level of 1.25 ppm for residues of
methoxyfenozide in/on pome fruit. EPA concludes that the proposed
tolerance must be raised to 1.5 ppm for methoxyfenozide in/on the
``Crop Group 11; Pome Fruits Group.''
2. Magnitude of the residue in cotton. An adequate number of
geographically representative field trials were submitted to support
the proposed use on cotton. These studies were conducted via use
patterns approximating those proposed by this petition. The results of
the cotton field trials indicate that residues of methoxyfenozide will
not exceed the proposed tolerance level of 2.0 ppm in/on cottonseed
when treated as proposed. Residues of methoxyfenozide ranged from 0.060
to 1.8 ppm in/on cottonseed treated with the 80% WP formulation
according to the maximum proposed use pattern. Residues of
methoxyfenozide did not vary significantly in cotton treated with ULV
spray applications (1 GPA) versus standard volume applications (10-30
GPA). Residues ranged from 0.13 to 0.32 ppm and from 0.12 to 0.66 ppm
in/on cotton treated in side-by-side plots with ULV and standard volume
applications, respectively. Rohm and Haas Company requested the
proposed tolerance on cottonseed at 2.0 ppm. However, EPA has
determined that it should be ``cotton, undelinted seed'' at 2.0 ppm.
The results of the cotton field trials indicate that residues of
methoxyfenozide may exceed the proposed tolerance level of 25 ppm in/on
cotton gin byproducts when treated as proposed. Residues of
methoxyfenozide ranged from 3.8 to 31.2 ppm in/on cotton gin byproducts
treated with the 80% WP formulation
[[Page 41363]]
according to the maximum proposed use pattern. Based on these data, the
tolerance for residues of methoxyfenozide in/on cotton gin byproducts
must be raised to 35 ppm.
3. Magnitude of the residue in apple processed commodities. The
submitted apple processing data are adequate for the purposes of this
petition. Residues of methoxyfenozide did not concentrate in juice but
concentrated 6x in wet pomace processed from whole apples bearing
detectable residues. Based on the results of the apple processing
study, a tolerance for residues of methoxyfenozide in apple juice is
not required. Rohm and Haas proposed a tolerance level of 7.5 ppm for
residues of methoxyfenozide in/on apple wet pomace. The maximum residue
level of methoxyfenozide expected in apple wet pomace was 6.06 ppm,
calculated by multiplying the HAFT residue (1.01 ppm; see apple field
trial) and the observed concentration factor (6x). Based on this
calculation, a tolerance of 7.0 ppm for residues of methoxyfenozide in/
on ``apple pomace, wet'' is appropriate.
4. Magnitude of the residue in cottonseed processed commodities.
The submitted cotton processing data are adequate for the purposes of
this petition. No concentration of methoxyfenozide residues was
observed in hulls, meal, and oil processed from undelinted cottonseed
bearing detectable residues. Based on the results of the current
processing study, tolerances for residues of methoxyfenozide in the
processed commodities of cotton are not required.
5. Residues in meat, milk, poultry, and eggs. The submitted dairy
cattle feeding study is adequate for the purpose of establishing
tolerances for secondary transfer of methoxyfenozide residues in milk
and ruminant tissues. EPA has determined that the residues of concern
in milk and ruminant tissues (except kidney and liver) are the parent
compound, methoxyfenozide. For liver and kidney, the residues of
concern are the parent compound, methoxyfenozide, and its metabolite
RH-141,518. EPA concludes that residues of methoxyfenozide are not
likely to exceed the proposed tolerances of 0.02 ppm in the milk and
meat of cattle, goats, hogs, horses, and sheep. EPA further concludes
that residues of methoxyfenozide are not likely to exceed the proposed
tolerance of 0.1 ppm in the fat of cattle, goats, hogs, horses, and
sheep as a result of the proposed uses. EPA also concludes that
residues of methoxyfenozide and its metabolite RH--141,518 are not
likely to exceed 0.1 ppm in liver and 0.02 ppm in meat byproduct
(except liver) of cattle, goat, hogs, horses, and sheep. The proposed
tolerances did not include residues in tissues of horses. However,
horses must be a part of the tolerance.
Rohm and Haas Company requested a waiver from the requirements to:
(i) Conduct a poultry feeding study; (ii) propose tolerances for
methoxyfenozide residues of concern in eggs and poultry tissues; and
(iii) provide enforcement method(s) for determination of
methoxyfenozide residues of concern in eggs and poultry tissues. The
waiver request is based on the maximum theoretical dietary burden of
methoxyfenozide for poultry animals as well as the results of the
poultry metabolism study. The only poultry feed item associated with
this petition is cotton meal, which would contribute a maximum
theoretical dietary burden for methoxyfenozide at 0.4 ppm.
The poultry metabolism study reviewed in this petition was
conducted at feeding levels of 58 ppm (MOP-label), 60 ppm (DMP-label),
and 68 ppm (TB-label) which are equivalent to 145x, 150x, and 170x,
respectively, the maximum theoretical dietary burden for poultry.
Assuming a linear relationship between dose and residues, the expected
residues in eggs and poultry tissues would be below the LOD for methods
used to measure residues in poultry products. EPA concludes that there
is no reasonable expectation of finite residues in eggs and poultry
tissues and that a poultry feeding study is not required at this time.
However, should the dietary burden for poultry increase due to the
addition of methoxyfenozide-treated poultry feed items through new
uses, a poultry feeding study may be required. If a poultry feeding
study is required in the future, then all tissues should be analyzed
for residues of methoxyfenozide and its metabolite RH-141,518.
D. International Residue Limits
There are no established or proposed Codex, Canadian or Mexican
limits for residues of methoxyfenozide in/on plant or animal
commodities. Therefore, no compatibility issues exist with regard to
the proposed U.S. tolerances discussed in this petition review.
E. Rotational Crop Restrictions
A confined rotational crop study was submitted and reviewed. The
petitioner has proposed a 30-day plantback interval for all crops not
listed on the product label. The confined rotational crop study
demonstrated that methoxyfenozide may accumulate in rotational crop
commodities at > 0.01 ppm at 30- and 90-day plantback intervals. The
rotational crop restrictions included on the submitted label are not
adequate. The label must include the following rotational crop
restrictions: Cotton may be rotated to treated fields at any time.
Leafy vegetables (except Brassica vegetables) and root and tuber
vegetables may be rotated to treated fields 1-year following
application of methoxyfenozide. Rotation to all other crops is
prohibited.
V. Conclusion
Therefore, the tolerances are established for residues of
methoxyfenozide in or on cotton, undelinted seed; cotton gin
byproducts; pome fruit; apple pomace, wet; milk; meat of cattle, goats,
hogs, horses and sheep and fat of cattle, goats, hogs, horses and sheep
at 2.0, 35.0, 1.5, 7.0, 0.02, 0.02, 0.1 ppm respectively and for the
combined residues of methoxyfenozide and its glucuronide metabolite in
liver of cattle, goats, hogs, horses and sheep and meat byproducts
(except liver) of cattle, goats, hogs, horses and sheep at 0.1 and 0.02
ppm respectively.
VI. Objections and Hearing Requests
Under section 408(g) of the FFDCA, as amended by the FQPA, any
person may file an objection to any aspect of this regulation and may
also request a hearing on those objections. The EPA procedural
regulations which govern the submission of objections and requests for
hearings appear in 40 CFR part 178. Although the procedures in those
regulations require some modification to reflect the amendments made to
the FFDCA by the FQPA of 1996, EPA will continue to use those
procedures, with appropriate adjustments, until the necessary
modifications can be made. The new section 408(g) provides essentially
the same process for persons to ``object'' to a regulation for an
exemption from the requirement of a tolerance issued by EPA under new
section 408(d), as was provided in the old FFDCA sections 408 and 409.
However, the period for filing objections is now 60 days, rather than
30 days.
A. What Do I Need to Do to File an Objection or Request a Hearing?
You must file your objection or request a hearing on this
regulation in accordance with the instructions provided in this unit
and in 40 CFR part 178. To ensure proper receipt by EPA, you must
identify docket control number OPP-300983 in the subject line on the
first page of your submission. All requests must be in writing, and
must be
[[Page 41364]]
mailed or delivered to the Hearing Clerk on or before September 5,
2000.
1. Filing the request. Your objection must specify the specific
provisions in the regulation that you object to, and the grounds for
the objections (40 CFR 178.25). If a hearing is requested, the
objections must include a statement of the factual issues(s) on which a
hearing is requested, the requestor's contentions on such issues, and a
summary of any evidence relied upon by the objector (40 CFR 178.27).
Information submitted in connection with an objection or hearing
request may be claimed confidential by marking any part or all of that
information as CBI. Information so marked will not be disclosed except
in accordance with procedures set forth in 40 CFR part 2. A copy of the
information that does not contain CBI must be submitted for inclusion
in the public record. Information not marked confidential may be
disclosed publicly by EPA without prior notice.
Mail your written request to: Office of the Hearing Clerk (1900),
Environmental Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania
Ave., NW., Washington, DC 20460. You may also deliver your request to
the Office of the Hearing Clerk in Rm. M3708, Waterside Mall, 401 M
St., SW., Washington, DC 20460. The Office of the Hearing Clerk is open
from 8 a.m. to 4 p.m., Monday through Friday, excluding legal holidays.
The telephone number for the Office of the Hearing Clerk is (202) 260-
4865.
2. Tolerance fee payment. If you file an objection or request a
hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or
request a waiver of that fee pursuant to 40 CFR 180.33(m). You must
mail the fee to: EPA Headquarters Accounting Operations Branch, Office
of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please
identify the fee submission by labeling it ``Tolerance Petition Fees.''
EPA is authorized to waive any fee requirement ``when in the
judgement of the Administrator such a waiver or refund is equitable and
not contrary to the purpose of this subsection.'' For additional
information regarding the waiver of these fees, you may contact James
Tompkins by phone at (703) 305-5697, by e-mail at tompkins.jim@epa.gov,
or by mailing a request for information to Mr. Tompkins at Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW.,
Washington, DC 20460.
If you would like to request a waiver of the tolerance objection
fees, you must mail your request for such a waiver to: James Hollins,
Information Resources and Services Division (7502C), Office of
Pesticide Programs, Environmental Protection Agency, Ariel Rios Bldg.,
1200 Pennsylvania Ave., NW., Washington, DC 20460.
3. Copies for the docket. In addition to filing an objection or
hearing request with the Hearing Clerk as described in Unit VI.A., you
should also send a copy of your request to the PIRIB for its inclusion
in the official record that is described in Unit I.B.2. Mail your
copies, identified by docket control number OPP-300983, to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW.,
Washington, DC 20460. In person or by courier, bring a copy to the
location of the PIRIB described in Unit I.B.2. You may also send an
electronic copy of your request via e-mail to: opp-docket@epa.gov.
Please use an ASCII file format and avoid the use of special characters
and any form of encryption. Copies of electronic objections and hearing
requests will also be accepted on disks in WordPerfect 6.1/8.0 file
format or ASCII file format. Do not include any CBI in your electronic
copy. You may also submit an electronic copy of your request at many
Federal Depository Libraries.
B. When Will the Agency Grant a Request for a Hearing?
A request for a hearing will be granted if the Administrator
determines that the material submitted shows the following: There is a
genuine and substantial issue of fact; there is a reasonable
possibility that available evidence identified by the requestor would,
if established resolve one or more of such issues in favor of the
requestor, taking into account uncontested claims or facts to the
contrary; and resolution of the factual issues(s) in the manner sought
by the requestor would be adequate to justify the action requested (40
CFR 178.32).
VII. Regulatory Assessment Requirements
This final rule establishes a tolerance under FFDCA section 408(d)
in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (October 4, 1993, 58 FR 51735). This final rule does not contain
any information collections subject to OMB approval under the Paperwork
Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose any enforceable
duty or contain any unfunded mandate as described under Title II of the
Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). Nor
does it require any prior consultation as specified by Executive Order
13084, entitled Consultation and Coordination with Indian Tribal
Governments (May 19, 1998, 63 FR 27655); special considerations as
required by Executive Order 12898, entitled Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations (February 16, 1994, 59 FR 7629); or require OMB review or
any Agency action under Executive Order 13045, entitled Protection of
Children from Environmental Health Risks and Safety Risks (April 23,
1997, 62 FR 19885). This action does not involve any technical
standards that would require Agency consideration of voluntary
consensus standards pursuant to section 12(d) of the National
Technology Transfer and Advancement Act of 1995 (NTTAA), Public Law
104-113, section 12(d) (15 U.S.C. 272 note). Since tolerances and
exemptions that are established on the basis of a petition under FFDCA
section 408(d), such as the tolerance in this final rule, do not
require the issuance of a proposed rule, the requirements of the
Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et seq.) do not apply.
In addition, the Agency has determined that this action will not have a
substantial direct effect on States, on the relationship between the
national government and the States, or on the distribution of power and
responsibilities among the various levels of government, as specified
in Executive Order 13132, entitled Federalism (August 4, 1999, 64 FR
43255). Executive Order 13132 requires EPA to develop an accountable
process to ensure ``meaningful and timely input by State and local
officials in the development of regulatory policies that have
federalism implications.'' ``Policies that have federalism
implications'' is defined in the Executive Order to include regulations
that have ``substantial direct effects on the States, on the
relationship between the national government and the States, or on the
distribution of power and responsibilities among the various levels of
government.'' This final rule directly regulates growers, food
processors, food handlers and food retailers, not States. This action
does not alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of FFDCA section 408(n)(4).
[[Page 41365]]
VIII. Submission to Congress and the Comptroller General
The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. EPA will submit a report containing this rule and other
required information to the U.S. Senate, the United States House of
Representatives, and the Comptroller General of the United States prior
to publication of this final rule in the Federal Register. This final
rule is not a ``major rule'' as defined by 5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: June 13, 2000.
Suzan B. Hazen,
Acting Director, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 321(q), (346a) and 371.
2. Section 180.544 is added to read as follows:
Sec. 180.544 Methoxyfenozide; tolerances for residues.
(a) General. (1) Tolerances are established for residues of the
insecticide methoxyfenozide; benzoic acid, 3-methoxy-2-methyl-2-(3,5-
dimethylbenzoyl)-2-(1,1-dimethylethyl)hydrazide in or on the following
agricultural commodities:
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Apple pomace, wet.......................................... 7.0
Cotton gin byproducts...................................... 35
Cotton, undelinted seed.................................... 2.0
Fat of cattle, goats, hogs, horses and sheep............... 0.1
Meat of cattle, goats, hogs, horses and sheep.............. 0.02
Milk....................................................... 0.02
Pome fruits crop group..................................... 1.5
------------------------------------------------------------------------
(2) Tolerances are established for the combined residues of
methoxyfenozide; benzoic acid, 3-methoxy-2-methyl-2-(3,5-
dimethylbenzoyl)-2-(1,1-dimethylethyl)hydrazide and its glucuronide
metabolite in or on the following agricultural commodities:
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Liver of cattle, goats, hogs, horses and sheep............. 0.1
Meat byproducts (except liver) of cattle, goats, hogs, 0.02
horses and sheep..........................................
------------------------------------------------------------------------
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 00-16801 Filed 7-3-00; 8:45 am]
BILLING CODE 6560-50-F
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