[Federal Register: October 13, 2004 (Volume 69, Number 197)]
[Rules and Regulations]
[Page 60820-60828]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr13oc04-12]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-2004-0299; FRL-7681-8]
Mepanipyrim; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes a tolerance for combined residues
of mepanipyrim, 4-methyl-N-phenyl-6-(1-propynyl)-2-pyrimidinamine, and
its metabolite, 4-methyl-N-phenyl-6-(2-hydroxypropyl)-2-pyrimidinamine,
both free and conjugated in or on grape; grape, raisin; strawberry; and
tomato. K-I Chemical U.S.A., Inc., requested these tolerances under the
Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the Food
Quality Protection Act of 1996 (FQPA).
DATES: This regulation is effective October 13, 2004. Objections and
requests for hearings must be received on or before December 13, 2004.
ADDRESSES: To submit a written objection or hearing request follow the
detailed instructions as provided in Unit VI. of the SUPPLEMENTARY
INFORMATION. EPA has established a docket for this action under Docket
identification (ID) number OPP-2004-0299. All documents in the docket
are listed in the EDOCKET index at http://www.epa.gov/edocket/.
Although listed in the index, some information is not publicly
available, i.e., CBI or other information whose disclosure is
restricted by statute. Certain other material, such as copyrighted
material, is not placed on the Internet and will be publicly available
only in hard copy form. Publicly available docket materials are
available either electronically in EDOCKET or in hard copy at the
Public Information and Records Integrity Branch (PIRIB), Rm. 119,
Crystal Mall 2, 1801 South Bell St., Arlington, VA. This
docket facility is open from 8:30 a.m. to 4 p.m., Monday through
Friday, excluding legal holidays. The docket telephone number is (703)
305-5805.
FOR FURTHER INFORMATION CONTACT: Mary L. Waller, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 308-9354; e-mail address: waller.mary@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
Crop production (NAICS 111), e.g., agricultural workers;
greenhouse, nursery, and floriculture workers; farmers.
Animal production (NAICS 112), e.g., cattle ranchers and
farmers, dairy cattle farmers, livestock farmers.
Food manufacturing (NAICS 311), e.g., agricultural
workers; farmers; greenhouse, nursery, and floriculture workers;
ranchers; pesticide applicators.
Pesticide manufacturing (NAICS 32532), e.g., agricultural
workers; commercial applicators; farmers; greenhouse, nursery, and
floriculture workers; residential users.
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 this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.
B. How Can I Access Electronic Copies of this Document and Other
Related Information?
In addition to using EDOCKET (http://www.epa.gov/edocket/), you may
access this Federal Register document electronically through the EPA
Internet under the ``Federal Register'' listings at http://www.epa.gov/fedrgstr/.
A frequently updated electronic version of 40 CFR part 180
is available at E-CFR Beta Site Two at http://www.gpoaccess.gov/ecfr/.
To access the OPPTS Harmonized Guidelines referenced in this document,
go directly to the guidelines at http://www.epa.gpo/opptsfrs/home/guidelin.htm/
.
II. Background and Statutory Findings
In the Federal Register of May 26, 2004 (69 FR 29940) (FRL-7357-4),
EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21 U.S.C.
346a(d)(3), announcing the filing of a pesticide petition (PP 8E5017)
by K-I Chemical U.S.A., Inc., 11 Martine Ave., 9\th\ Floor, White
Plains, NY 10606. That notice included a summary of the petition
prepared by K-I Chemical U.S.A., the petitioner. One comment from a
private citizen was received in response to the notice of filing. The
petition requested that 40 CFR part 180 be amended by establishing
tolerances for combined residues of the fungicide mepanipyrim in or on
grape at 2.0 parts per million (ppm); grape, raisin at 4.0 ppm;
strawberry at 1.5 ppm; and tomato at 0.5 ppm.
Section 408(b)(2)(A)(i) of 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) of FFDCA 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
[[Page 60821]]
408(b)(2)(C) of FFDCA 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 of FFDCA and a complete
description of the risk assessment process, see the final rule on
Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997) (FRL-
5754-7).
III. Aggregate Risk Assessment and Determination of Safety
Consistent with section 408(b)(2)(D) of FFDCA, 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) of FFDCA, for tolerances for combined residues of mepanipyrim
and its metabolite in or on grape at 1.5 ppm; grape, raisin at 3.0 ppm;
strawberry at 1.5 ppm; and tomato at 0.5 ppm. EPA's assessment of
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 mepanipyrim are
discussed in Table 1 of this unit as well as the no-observed-adverse-
effect-level (NOAEL) and the lowest-observed-adverse-effect-level
(LOAEL) from the toxicity studies reviewed.
Table 1.--Subchronic, Chronic, and Other Toxicity
----------------------------------------------------------------------------------------------------------------
Guideline No. Study Type Results
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870.3100 90-Day oral toxicity NOAEL = >= 55.9/61.3 milligrams/kilogram/
rodents (rat) day
LOAEL = Not established
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870.3100 90-Day oral toxicity NOAEL = Not established
rodents (rat) LOAEL = 109/120 mg/kg/day, based on
increased total bilirubin, alkaline
phosphatase, phospholipids, non-esterified
fatty acids in males; increased fatty
liver changes in both sexes; decreased
food efficiency, triglycerides, and
phospholipids and increased incidence of
hepatic abnormalities (yellowish,
malformative nodules, granulation,
hepatodiaphragmatic nodule, and fatty
change) in females.
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870.3100 90-Day oral toxicity NOAEL = 182/224/mg/kg/day
rodents (mouse) LOAEL = 603/675 mg/kg/day (male/female (M/
F)), based on increased absolute and
relative (to body) liver weights in both
sexes, increased severity of
anisonucleosis in male liver, and
increased food consumption in males.
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870.3150 90-Day oral toxicity in NOAEL = Not established
nonrodents (dog) LOAEL = 15 mg/kg/day (M/F), based on
increased incidences of minimal pigment
deposition in the Kupffer cells and
hepatocytes and increased alanine
aminotransferase in both sexes.
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870.3150 90-Day oral toxicity in NOAEL = 7.5 mg/kg/day
nonrodents (dog) LOAEL = Not established
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870.3700 Prenatal developmental in Maternal NOAEL = 750/mg/kg/day
rodents (rat) LOAEL was not established.
Developmental NOAEL = 750 mg/kg/day
LOAEL was not established.
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870.3700 Prenatal developmental in Maternal NOAEL = 90/mg/kg/day
nonrodents (rabbit) LOAEL was not established.
Developmental NOAEL = 90 mg/kg/day
LOAEL was not established.
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870.3800 Reproduction and fertility Parental/Systemic NOAEL = 3.7/mg/kg/day
effects (rats) LOAEL = 11.2/12.7 mg/kg/day, based on
increased incidence of periacinar
hepatocytic fatty vacuolation in the P and
F1 generation males.
Reproductive NOAEL = 11.2/12.7 mg/kg/day
LOAEL was not established.
Offspring NOAEL = 3.7/4.2/mg/kg/day
LOAEL 11.2/12.7 mg/kg/day, based on focal
inflammation with associated hepatocytic
vacuolation in the males, periacinar/
panacinar hepatocytic fatty vacuolation
and increased absolute liver eights in the
females, and increased relative (to body)
liver weights in both sexes.
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[[Page 60822]]
870.3800 Reproduction and fertility Parental/Systemic NOAEL was not
effects (rats) established.
LOAEL = 10.5/12.0 mg/kg/day (M/F), based on
increased incidence of periacinar
hepatocytic fatty vacuolation in the F1
males.
Reproductive NOAEL = 141.9/165.7/mg/kg/day
(M/F)
LOAEL was not established.
Offspring NOAEL = 3.7/4.2 mg/kg/day (M/F)
LOAEL = 10.5/12.0 mg/kg/day (M/F), based on
increased liver weights, macroscopic
hepatic findings (accentuated lobular
pattern and pale liver), and hepatocytic
fatty vacuolation.
----------------------------------------------------------------------------------------------------------------
870.4300 Combined chronic toxicity/ NOAEL = 7.34/9.29/mg/kg/day
carcinogenicity rodents LOAEL = 100/125 mg/kg/day based on
(rat) increased incidence of clinical signs of
toxicity in males, decreased body weight,
body weight gain and food efficiency in
both sexes, and evidence of
hepatotoxicity, nephrotoxicity, and fatty
acid/lipid metabolism disruption in both
sexes.
Evidence of carcinogenicity, based on
hepatocellular adenomas in females.
----------------------------------------------------------------------------------------------------------------
870.4100 Chronic toxicity dogs NOAEL = 7.5 mg/kg/day
LOAEL = 50 mg/kg/day (M/F), based on
decreased body weights, body weight gains,
and food consumption in females; increased
leukocytes (neutrophils and lymphocytes),
decreased erythroid series, and increased
myeloid to erythroid ratio in both sexes;
and indications of liver toxicity,
including increased ALT, alkaline
phosphatase, and ornithine carbamyl
transferase, and lipofuscin, enlargement,
and inflammatory infiltrate in the
hepatocytes of both sexes.
----------------------------------------------------------------------------------------------------------------
870.4300 Carcinogenicity mice NOAEL = 56/68 (M/F) mg/kg/day
LOAEL = 578/681 mg/kg/day (M/F), based on
decreased body weights, body weight gains,
and food efficiency in males, absolute and
relative to body liver weights in both
sexes, and gross and microscopic hepatic
lesions in both sexes.
Evidence of carcinogenicity, based on
hepatocellular adenomas and carcinomas in
male and female mice.
----------------------------------------------------------------------------------------------------------------
870.5100 Reverse gene mutation There was no evidence of induced mutant
assay in bacteria colonies over background.
----------------------------------------------------------------------------------------------------------------
870.5300 Forward gene mutation There was no evidence that KIF 3535 induced
assay in mammalian cells mutant colonies over background in the
S9 activation.
----------------------------------------------------------------------------------------------------------------
870.5375 In vitro mammalian Not clastogenic with or without S9
cytogenetic assay activation, at any dose tested.
----------------------------------------------------------------------------------------------------------------
870.5385 In vivo mammalian No increase in aberrant cells were seen in
cytogenetic assay the bone marrow chromosomal aberration
assay.
----------------------------------------------------------------------------------------------------------------
870.5395 In vivo mammalian Did not induce micronucleated polychromatic
cytogenetic assay erythrocytes (PMCEs) in bone marrow at any
dose.
----------------------------------------------------------------------------------------------------------------
870.5500 Bacterial DNA damage and No evidence that DNA damage was induced.
repair test
----------------------------------------------------------------------------------------------------------------
870.5550 UDS synthesis in mammalian Did not induce UDS at any dose.
cell culture
----------------------------------------------------------------------------------------------------------------
870.7485 Metabolism and In an unacceptable rat metabolism study
pharmacokinetics (rat) mepanipyrim was readily absorbed from the
gastrointestinal tract and about 96% of
the administered dose was eliminated in
feces and urine. Bile was the major route
of excretion (72%); and less than 0.1% of
the dose was eliminated in expired air.
There was no sex difference in absorption
and elimination of mepanipyrim. Parent and
up to 16 metabolites were purported to be
identified; however, > 5% of the
administered dose was not accounted or
analyzed in the excreta.
----------------------------------------------------------------------------------------------------------------
Non-guideline Mechanism of fatty liver Dietary administration of 4,000 ppm KIF
(rats) 3535 to male rats may cause fatty liver by
a mechanism inhibiting the synthesis and/
or transport and release of VLDL from the
liver, as demonstrated by decreased
acetate incorporation, decreased serum
lipid concentrations, increased liver
lipid concentrations, decreased VLDL, LDL,
and HDL-triglycerides and HDL-cholesterol
levels in serum, and decreased adipose
tissue weight.
----------------------------------------------------------------------------------------------------------------
[[Page 60823]]
Non-guideline Oxidative damage to Measurement of liver 8-hydroxyguanine were
hepatic DNA (females rats inconsistent and not accompanied by
and mice) vehicle control data, therefore,
interpretation of the results were
inconclusive.
----------------------------------------------------------------------------------------------------------------
Non-guideline Induction of lipid Oral or dietary administration of the test
peroxidation (female rats compound did not induce hepatic lipid
and mice) peroxidation as measured by thiobarbituric
acid-reactive compounds in either female
rats or mice in this study.
----------------------------------------------------------------------------------------------------------------
Non-guideline Induction of mixed Dietary administration of mepanipyrim
function oxidase (female induced cytochrome P-450 and aminopyrine N-
rats and mice) demthylase activities in the female rat
and aminopyrine N-demthylase activity in
female mice.
----------------------------------------------------------------------------------------------------------------
Non-guideline Promotion of liver Liver is the target organ, consistent with
carcinogenesis (rats) other studies. The test compound may/or
may not act as a tumor promoting agent in
the two-stage model of hepatic
carcinogenesis utilized in the current
study.
----------------------------------------------------------------------------------------------------------------
Non-guideline Liver enzyme induction Single oral administration of 5000 mg/kg or
(mice) multiple administrations of 3000 mg/kg/day
KIF-3535 to male mice causes
hepatotoxicity (increased liver weights,
cellular hypertrophy, and increase in cell
proliferation) and increase in liver
metabolic enzymes (cytochrome P-450).
----------------------------------------------------------------------------------------------------------------
Non-guideline Liver enzyme induction Single administration of 5,000 mg/kg or
(rat) multiple administrations of 2,000 mg/kg
KIF-3535 to rats caused decrease in body
weights, hepatotoxicity (increased liver
weights, discoloration, cellular
hypertrophy, fatty changes, elevated GPT
and GOT, and increase in cell
proliferation) and increase in mild
increase in liver metabolic enzymes
(cytochrome P-450).
----------------------------------------------------------------------------------------------------------------
B. Toxicological Endpoints
The dose at which no adverse effects are observed (the NOAEL) from
the toxicology study identified as appropriate for use in risk
assessment is used to estimate the toxicological level of concern
(LOC). However, the lowest dose at which adverse effects of concern are
identified (the LOAEL) is sometimes used for risk assessment if no
NOAEL was achieved in the toxicology study selected. An uncertainty
factor (UF) is applied to reflect uncertainties inherent in the
extrapolation from laboratory animal data to humans and in the
variations in sensitivity among members of the human population as well
as other unknowns. An UF of 100 is routinely used, 10X to account for
interspecies differences and 10X for intraspecies differences.
Three other types of safety or uncertainty factors may be used:
``Traditional uncertainty factors;'' the ``special FQPA safety
factor;'' and the ``default FQPA safety factor.'' By the term
``traditional uncertainty factor,'' EPA is referring to those
additional uncertainty factors used prior to FQPA passage to account
for database deficiencies. These traditional uncertainty factors have
been incorporated by the FQPA into the additional safety factor for the
protection of infants and children. The term ``special FQPA safety
factor'' refers to those safety factors that are deemed necessary for
the protection of infants and children primarily as a result of the
FQPA. The ``default FQPA safety factor'' is the additional 10X safety
factor that is mandated by the statute unless it is decided that there
are reliable data to choose a different additional factor (potentially
a traditional uncertainty factor or a special FQPA safety factor).
For dietary risk assessment (other than cancer) the Agency uses the
UF to calculate an acute or chronic reference dose (acute RfD or
chronic RfD) where the RfD is equal to the NOAEL divided by an UF of
100 to account for interspecies and intraspecies differences and any
traditional uncertainty factors deemed appropriate (RfD = NOAEL/UF).
Where a special FQPA safety factor or the default FQPA safety factor is
used, this additional factor is applied to the RfD by dividing the RfD
by such additional factor. The acute or chronic Population Adjusted
Dose (aPAD or cPAD) is a modification of the RfD to accommodate this
type of safety factor.
For non-dietary risk assessments (other than cancer) the UF is used
to determine the LOC. For example, when 100 is the appropriate UF (10X
to account for interspecies differences and 10X for intraspecies
differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to
exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and
compared to the LOC.
The linear default risk methodology (Q*) is the primary method
currently used by the Agency to quantify carcinogenic risk. The Q*
approach assumes that any amount of exposure will lead to some degree
of cancer risk. A Q* is calculated and used to estimate risk which
represents a probability of occurrence of additional cancer cases
(e.g., risk). An example of how such a probability risk is expressed
would be to describe the risk as one in one hundred thousand (1 X
10-\5\), one in a million (1 X 10-\6\), or one in
ten million (1 X 10-\7\). Under certain specific
circumstances, MOE calculations will be used for the carcinogenic risk
assessment. In this non-linear approach, a ``point of departure'' is
identified below which carcinogenic effects are not expected. The point
of departure is typically a NOAEL based on an endpoint related to
cancer effects though it may be a different value derived from the dose
response curve. To estimate risk, a ratio of the point of departure to
exposure (MOE\cancer\ = point of departure/exposures) is calculated.
A summary of the toxicological endpoints for mepanipyrim used for
human risk assessment is shown in Table 2 of this unit:
[[Page 60824]]
Table 2.--Summary of Toxicological Dose and Endpoints for Mepanipyrim Human Health Risk Assessment
----------------------------------------------------------------------------------------------------------------
FQPA SF* and Level of
Exposure Scenario Dose Used in Risk Concern for Risk Study and Toxicological
Assessment, UF Assessment Effects
----------------------------------------------------------------------------------------------------------------
Acute Dietary Not available None An endpoint of concern
attributable to a
single dose was not
identified. An acute
RfD was not
established.
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Chronic Dietary all populations NOAEL= 7.3 mg/kg/day FQPA SF = 1X Chronic Toxicity - Rat
UF = 100............... cPAD = chronic RfD..... Systemic Toxicity LOAEL
Chronic RfD = 0.073 mg/ FQPA SF = 0.073 mg/kg/ = 100 mg/kg/day, based
kg/day. day. on increased incidence
of clinical signs of
toxicity in males,
decreased body weight,
body weight gain and
food efficiency in
both sexes, and
evidence of
hepatotoxicity,
nephrotoxicity, and
fatty acid/lipid
metabolism disruption
in both sexes.
----------------------------------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation) EPA concluded that
mepanipyrim is
``likely to be
carcinogenic to
humans.'' For risk
assessment purposes
EPA derived a Q1*=
1.35 x 10-\2\, based
on mouse liver
combined adenomas and
carcinomas.
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C. Exposure Assessment
1. Dietary exposure from food and feed uses. Mepanipyrim is a new
chemical and these are the first tolerances to be proposed for this
chemical. Risk assessments were conducted by EPA to assess dietary
exposures from mepanipyrim in food as follows:
i. Acute exposure. 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 one-day
or single exposure. There were no toxic effects attributable to a
single dose. An endpoint of concern was not identified to quantitate
acute dietary risk to the general population, including infants and
children, or to the subpopulation females 13-50 years old. Therefore, a
quantitative acute exposure assessment was not performed.
ii. Chronic exposure. In conducting the chronic dietary risk
assessment EPA used the Dietary Exposure Evaluation Model software with
the Food Commodity Intake Database (DEEM-FCID\TM\), which incorporates
food consumption data as reported by respondents in the USDA 1994-1996
and 1998 Nationwide Continuing Surveys of Food Intake by Individuals
(CSFII), and accumulated exposure to the chemical for each commodity.
The following assumptions were made for the chronic exposure
assessments: It was assumed that 100% of the crop imported from Western
Europe was treated and that anticipated residues based on average field
trial data occurred on all commodities. Since the petitioner provided
pesticide product labels limited to use in Western Europe only, it was
assumed that use of mepanipyrim would be limited to Western Europe.
iii. Cancer. For the cancer exposure assessment, the same
assumptions as identified in the chronic exposure unit, Unit
III.C.1.ii., were used. Applying the Q1* of 0.0135 (mg/kg/
day)-\1\ to the exposure value results in a cancer risk
estimate of 2.6 x 10-\7\.
iv. Anticipated residue and percent crop treated (PCT) information.
Section 408(b)(2)(E) of FFDCA authorizes EPA to use available data and
information on the anticipated residue levels of pesticide residues in
food and the actual levels of pesticide chemicals that have been
measured in food. If EPA relies on such information, EPA must pursuant
to section 408(f)(1) of FFDCA require that data be provided 5 years
after the tolerance is established, modified, or left in effect,
demonstrating that the levels in food are not above the levels
anticipated. Following the initial data submission, EPA is authorized
to require similar data on a time frame it deems appropriate.
Section 408(b)(2)(F) of FFDCA states that the Agency may use data
on the actual percent of food treated for assessing chronic dietary
risk only if the Agency can make the following findings: Condition 1,
that the data used are reliable and provide a valid basis to show what
percentage of the food derived from such crop is likely to contain such
pesticide residue; Condition 2, that the exposure estimate does not
underestimate exposure for any significant subpopulation group; and
Condition 3, if data are available on pesticide use and food
consumption in a particular area, the exposure estimate does not
understate exposure for the population in such area. In addition, the
Agency must provide for periodic evaluation of any estimates used. To
provide for the periodic evaluation of the estimate of PCT as required
by section 408(b)(2)(F) of FFDCA, EPA may require registrants to submit
data on PCT.
The Agency used PCT information as follows: The percentage of
imported crops from Western Europe which are consumed by the United
States are as follows: Grapes, fresh - 1%; grape, juice - 1%; grape,
raisin - 3.3%; strawberry, fresh - 1%; strawberry, juice - 31.5%;
tomatoes, fresh - 1.3% and tomatoes, processed - 4%.
The Agency believes that the three conditions listed in Unit III.
have been met. With respect to Condition 1, the PCT estimates were
derived from the U.S. Department of Agriculture's Economic Service and
the U.S. Census Bureau for the period of 1981-2000 to determine the
imported share of U.S. consumed food. Additionally, import data from
the Foreign Agricultural Trade of the United States (FATUS) database
which is used as the official United States source of import and export
data served as the source to determine the percentage of imported
grapes, strawberries, and tomatoes imported from Western Europe. Import
data from the years 2000 to 2003 was analyzed and averaged in order to
estimate the percentage of imports. The Agency believes this data is
reliable as the import data was stable over a 3 year period, and the
United States has other major sources favored for import of these
commodities. As to Conditions 2 and 3, regional consumption information
and consumption
[[Page 60825]]
information for significant subpopulations is taken into account
through EPA's computer-based model for evaluating the exposure of
significant subpopulations including several regional groups. Use of
this consumption information in EPA's risk assessment process ensures
that EPA's exposure estimate does not understate exposure for any
significant subpopulation group and allows the Agency to be reasonably
certain that no regional population is exposed to residue levels higher
than those estimated by the Agency. Other than the data available
through national food consumption surveys, EPA does not have available
information on the regional consumption of food to which mepanipyrim
may be applied in a particular area.
2. Dietary exposure from drinking water. The proposed tolerances
are for imported commodities only, and there are no current or proposed
U.S. registrations for this chemical. Therefore, there is no potential
for exposure to mepanipyrim through drinking water, and a drinking
water assessment was not performed.
3. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pets). There are no products
containing mepanipyrim proposed or registered for residential use or
that may be applied by commercial applicators to residential sites.
Therefore, a residential exposure assessment was not performed.
4. Cumulative effects from substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of FFDCA 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.''
Unlike other pesticides for which EPA has followed a cumulative
risk approach based on a common mechanism of toxicity, EPA has not made
a common mechanism of toxicity finding as to mepanipyrim and any other
substances and mepanipyrim 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 mepanipyrim 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 policy statements released by EPA's OPP concerning
common mechanism determinations and procedures for cumulating effects
from substances found to have a common mechanism on EPA's web site at
http://www.epa.gov/pesticides/cumulative/.
D. Safety Factor for Infants and Children
1. In general. Section 408 of FFDCA 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 database on toxicity and exposure
unless EPA determines based on reliable data 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
MOE analysis or through using uncertainty (safety) factors in
calculating a dose level that poses no appreciable risk to humans. In
applying this provision, EPA either retains the default value of 10X
when reliable data do not support the choice of a different factor, or,
if reliable data are available, EPA uses a different additional safety
factor value based on the use of traditional uncertainty factors and/or
special FQPA safety factors, as appropriate.
2. Prenatal and postnatal sensitivity. There is no quantitative or
qualitative evidence of increased susceptibility of rat and rabbit
fetuses to in utero exposure to mepanipyrim in developmental studies.
There is no quantitative or qualitative evidence of increased
susceptibility to mepanipyrim following pre-/postnatal exposure in a 2-
generation reproduction study. There is no concern for developmental
neurotoxicity resulting from exposure to mepanipyrim. Since there was
no observed evidence of developmental neurotoxicity in short and long-
term toxicity studies in rats, mice, and dogs, a developmental
neurotoxicity (DNT) study is not required.
3. Conclusion. There is a complete toxicity database for
mepanipyrim and exposure data are complete or are estimated based on
data that reasonably accounts for potential exposures. There is no
evidence of susceptibility following in utero exposure in the
developmental toxicity studies in rats or rabbits, and in the 2-
generation rat reproduction study. There are no residual uncertainties
concerning pre- and postnatal toxicity and no neurotoxicity concerns.
The chronic and cancer dietary food exposure assessments utilizes ARs
calculated from field trial data and percent crop imported from Western
Europe data for all commodities. Although refined, the assessments are
based on reliable data and will not underestimate exposure/risk. There
is no potential for drinking water exposure. There is no potential for
residential exposure. Based on these data and conclusions, EPA reduced
the FQPA Safety Factor to 1X and a developmental neurotoxicity study
will not be required.
E. Aggregate Risks and Determination of Safety
1. Acute risk. An acute endpoint was not identified in any of the
toxicity studies. Therefore, no acute risk is expected from exposure to
mepanipyrim.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
mepanipyrim from food will utilize < 1% of the cPAD for the U.S.
population, < 1% of the cPAD for all infants < 1 year old, and < 1 % of
the cPAD for children 1-2 years old. There are no residential uses for
mepanipyrim that result in chronic residential exposure to mepanipyrim.
There are no current or proposed U.S. registrations of mepanipyrim for
the United States and, as a result, there is no expectation of exposure
through drinking water. Therefore, EPA does not expect the aggregate
exposure (dietary) to exceed 100% of the cPAD, as shown in Table 3 of
this unit:
Table 3.--Summary of Chronic Dietary Exposure and Risk for Mepanipyrim
----------------------------------------------------------------------------------------------------------------
Exposure (mg/kg/day) % cPAD
Population Subgroup cPAD (mg/kg/day) -------------------------------------------------
DEEM-FCID DEEM-FCID
----------------------------------------------------------------------------------------------------------------
General U.S. Population 0.73 19 < 1
----------------------------------------------------------------------------------------------------------------
[[Page 60826]]
All Infants < 1 year old) 0.73 0.000006 < 1
----------------------------------------------------------------------------------------------------------------
Children 1-2 years old 0.73 0.000051 < 1
----------------------------------------------------------------------------------------------------------------
Children 3-5 years old 0.73 0.000053 < 1
----------------------------------------------------------------------------------------------------------------
Children 6-12 years old 0.73 0.000028 < 1
----------------------------------------------------------------------------------------------------------------
Youth 13-19 years old 0.73 0.000013 < 1
----------------------------------------------------------------------------------------------------------------
Adults 20-49 years old 0.73 0.000015 < 1
----------------------------------------------------------------------------------------------------------------
Adults 50+ years old 0.73 0.000017 < 1
----------------------------------------------------------------------------------------------------------------
Females 13-49 years old 0.73 0.000015 < 1
----------------------------------------------------------------------------------------------------------------
3. Aggregate cancer risk for U.S. population. Applying the
Q1* of 0.0135 (mg/kg/day)-\1\ to the exposure
value results in a cancer risk estimate of 2.6 x 10-\7\.
Therefore, estimated cancer risk is below the Agency's level of concern
of risk in the range of 1 x 10-\6\.
4. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population, and toinfants and children from aggregate
exposure to mepanipyrim residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology (gas chromotography/nitrogen-
phosphorus detector (GC/NPD) method and multi-residue method (MRM)) is
available to enforce the tolerance expression. The method may be
requested from: Chief, Analytical Chemistry Branch, Environmental
Science Center, 701 Mapes Rd., Ft. Meade, MD 20755-5350; telephone
number: (410) 305-2905; e-mail address: residuemethods@epa.gov.
B. International Residue Limits
There are currently no established Codex, Canadian or Mexican
maximum residue limits (MRLs) for mepanipyrim.
V. Conclusion
Therefore, the tolerances are established for combined residues of
mepanipyrim, 4-methyl-N-phenyl-6-(1-propynyl)-2-pyrimidinamine, and its
metabolite, 4-methyl-N-phenyl-6-(2-hydroxypropyl)-2-pyrimidinamine,
both free and conjugated in or on grape at 1.5 ppm; grape, raisin at
3.0 ppm; strawberry at 1.5 ppm; and tomato at 0.5 ppm.
VI. Objections and Hearing Requests
Under section 408(g) of FFDCA, as amended by 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 FFDCA by FQPA, EPA
will continue to use those procedures, with appropriate adjustments,
until the necessary modifications can be made. The new section 408(g)
of FFDCA 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) of FFDCA, as was
provided in the old sections 408 and 409 of FFDCA. 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 ID number OPP-2004-0299 in the subject line on the
first page of your submission. All requests must be in writing, and
must be mailed or delivered to the Hearing Clerk on or before December
13, 2004.
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 (1900L),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001. You may also deliver your request to the
Office of the Hearing Clerk in Suite 350, 1099 14\th\ St., NW.,
Washington, DC 20005. 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) 564-6255.
2. 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 ADDRESSES. Mail your
copies, identified by docket ID number OPP-2004-0299, to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001. In person or by courier, bring a copy to the location of the
PIRIB described in ADDRESSES. You may also send an electronic copy of
your request via e-
[[Page 60827]]
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 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. Statutory and Executive Order Reviews
This final rule establishes a tolerance under section 408(d) of
FFDCA 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 (58 FR 51735, October 4, 1993). Because this rule has been
exempted from review under Executive Order 12866 due to its lack of
significance, this rule is not subject to Executive Order 13211,
Actions Concerning Regulations That Significantly Affect Energy Supply,
Distribution, or Use (66 FR 28355, May 22, 2001). 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 special considerations under Executive
Order 12898, entitled Federal Actions to Address Environmental Justice
in Minority Populations and Low-Income Populations (59 FR 7629,
February 16, 1994); or OMB review or any Agency action under Executive
Order 13045, entitled Protection of Children from Environmental Health
Risks and Safety Risks (62 FR 19885, April 23, 1997). 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 section 408(d) of FFDCA, 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(64 FR 43255, August 10, 1999). 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 section 408(n)(4) of FFDCA. For these same reasons, the
Agency has determined that this rule does not have any ``tribal
implications'' as described in Executive Order 13175, entitled
Consultation and Coordination with Indian Tribal Governments (65 FR
67249, November 6, 2000). Executive Order 13175, requires EPA to
develop an accountable process to ensure ``meaningful and timely input
by tribal officials in the development of regulatory policies that have
tribal implications.'' ``Policies that have tribal implications'' is
defined in the Executive order to include regulations that have
``substantial direct effects on one or more Indian tribes, on the
relationship between the Federal Government and the Indian tribes, or
on the distribution of power and responsibilities between the Federal
Government and Indian tribes.'' This rule will not have substantial
direct effects on tribal governments, on the relationship between the
Federal Government and Indian tribes, or on the distribution of power
and responsibilities between the Federal Government and Indian tribes,
as specified in Executive Order 13175. Thus, Executive Order 13175 does
not apply to this rule.
VIII. Congressional Review Act
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 U.S. 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: September 30, 2004.
James Jones,
Director, Office of Pesticide Programs.
0
Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
0
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
0
2. Section 180.604 is added to subpart C to read as follows:
Sec. 180.604 Mepanipyrim; tolerances for residues.
(a) General. [Reserved]
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect of inadvertent residues. [Reserved]
(e) Revoked tolerances subject to the channel of trade provisions.
[Reserved]
(f) Import tolerances. Tolerances are established for the combined
residues of mepanipyrim, 4-methyl-N-phenyl-6-(1-propynyl)-2-
pyrimidinamine, and its metabolite, 4-methyl-N-phenyl-6-(2-
hydroxypropylk)-2-pyrimidinamine,
[[Page 60828]]
both free and conjugated in or on the following commodities:
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Grape...................................................... 1.5
Grape, raisin.............................................. 3.0
Strawberry................................................. 1.5
Tomato..................................................... 0.5
------------------------------------------------------------------------
[FR Doc. 04-22963 Filed 10-12-04; 8:45 am]
BILLING CODE 6560-50-S