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Buprofezin - Pesticide Tolerances 8/01

ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-301159; FRL-6796-6]
RIN 2070-AB
Buprofezin; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for residues of
buprofezin (2-tert-butylimino-3-isopropyl-5-phenyl-1,3,5-thiadiazinan-
4-one) in or on almonds; banana; citrus; citrus, oil; citrus, dried
pulp; grape; grape, raisin; milk; fat (cattle, goats, hogs, horses,
sheep); meat byproducts (cattle, goats, hogs, horses, sheep); liver
(cattle, goats, hogs, horses, sheep). Aventis (formerly AgrEvo)
requested this tolerance under the Federal Food, Drug, and Cosmetic
Act, as amended by the Food Quality Protection Act of 1996. In
addition, this regulation also establishes time-limited tolerances for
residues of buprofezin (2-tert-butylimino-3-isopropyl-5-phenyl-1,3,5-
thiadiazinan-4-one) in or on almond, hulls; cotton, undelinted seed;
cotton, gin byproducts; and tomato. Aventis (formerly AgrEvo) requested
this tolerance under the Federal Food, Drug, and Cosmetic Act, as
amended by the Food Quality Protection Act of 1996. The tolerances will
expire on July 31, 2005.

DATES: This regulation is effective September 5, 2001. Objections and
requests for hearings, identified by docket control number OPP-301159,
must be received by EPA on or before November 5, 2001.

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 docket control number OPP-301159 in the
subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Richard J. Gebken,
Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460; telephone number: (703) 305-6701; and e-mail
address: gebken.richard@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
------------------------------------------------------------------------
Industry 111 Crop production
112 Animal production
311 Food manufacturing
32532 Pesticide
manufacturing
------------------------------------------------------------------------

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," "Regulations and Proposed Rules," and then look up the
entry for this document under the "Federal Register--Environmental
Documents." You can also go directly to theFederal Register listings
at http://www.epa.gov/fedrgstr/. To access the OPPTS Harmonized
Guidelines referenced in this document, go directly to the guidelines
at http://www.epa.gov/opptsfrs/home/guidelin.htm.
A frequently updated electronic version of 40 CFR part 180 is available at
http://www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/40cfr180_00.hhtml,
a beta site currently under development.
2. In person. The Agency has established an official record for
this action under docket control number OPP-301159. 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 June 21, 2000 (65 FR 38543) (FRL-6557-
3), EPA issued a notice pursuant to section 408 of the Federal Food,
Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a as amended by the Food
Quality Protection Act of 1996 (FQPA) (Public Law 104-170) announcing
the filing of a pesticide petition (PP) for tolerance by AgrEvo USA
Company, Little Falls Centre One, 2711 Centerville Road, Wilmington, DE
19808. This notice included a summary of the petition prepared by
Aventis (formerly AgrEvo), the registrant. There were no comments
received in response to the notice of filing.
The petition requested that 40 CFR 180.511 be amended by
establishing a tolerance for residues of the insecticide buprofezin in
or on almonds, nutmeats at 0.05 part per million (ppm); almonds, hulls,
at 0.7 ppm; bananas at 0.1 ppm, the citrus crop group, fruit, at 0.7
ppm, cotton seed at 1.0 ppm, grapes at 0.4 ppm, and tomatoes, fruit at
0.8 ppm; in or on the following processed commodities: citrus oil at 26
ppm; citrus pulp, dried, at 2.5 ppm; cotton gin by-products at 23 ppm;
and raisins at 1.0 ppm; and in or on the following meat and milk
commodities: the fat, meat and meat byproducts of cattle, goats, hogs,
horses, and sheep at 0.05 ppm; and milk at 0.01 ppm.
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 (62 FR 62961, November 26, 1997) (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 buprofezin, on almond;
banana; citrus; citrus, oil; citrus, dried pulp; grape; grape, raisin;
milk; fat (cattle, goats, hogs, horses, sheep); meat byproducts
(cattle, goats, hogs, horses, sheep); liver (cattle, goats, hogs,
horses, sheep); almond, hulls; cotton, undelinted seed; cotton, gin
byproducts and tomato at 0.05, 0.20, 2.0, 60, 6.0, 0.40, 0.60, 0.01,
0.05, 0.05, 0.05, 0.70, 0.40, 15, 0.40 ppm, respectively. 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 buprofezin are
discussed in the following Table 1 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
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Guideline No. Study Type Results
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870.3100 90-Day oral toxicity NOAEL = 13.0 mg/kg/day males
rodents NOAEL = 16.3 mg/kg/day females
LOAEL = 68.6 mg/kg/day males
LOAEL = 81.8 mg/kg/day females based on
increased relative thyroid weight for
males, increased liver weights for both
male and females, and increased
microscopic lesions in liver and thyroid
for both male and females.
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870.3200 24-Day dermal toxicity Systemic
NOAEL = 300 mg/kg/day
LOAEL = 1,000 mg/kg/day based on increased
focal necrosis with an inflammatory
infiltrate in liver for females.
Dermal
NOAEL = 300 mg/kg/day
LOAEL = 1,000 mg/kg/day based on increased
acanthosis and hyperkeratosis in skin for
females.
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870.3700 Prenatal developmental in Maternal
rodents NOAEL = 200 mg/kg/day
LOAEL = 800 mg/kg/day based on mortality,
decreased pregnancy rates, and increased
resorption rates.
Developmental
NOAEL = 200 mg/kg/day
LOAEL = 800 mg/kg/day based on reduced
ossification, reduced pup weight, fetal
edema.
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870.3700 Prenatal developmental in Maternal
non-rodents NOAEL = 50 mg/kg/day
LOAEL = 250 mg/kg/day based on decreased
food consumption, decreased body weights.
Developmental
NOAEL = 250 mg/kg/day
LOAEL = not established (less than 250 mg/
kg/day)
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870.3800 Reproduction and fertility Parental/systemic
effects NOAEL = 7.89 mg/kg/day
LOAEL = 81.47 mg/kg/day based on decreased
body weight gain and on organ weight
changes.
Reproductive
NOAEL = 7.89 mg/kg/day
LOAEL = 81.47 mg/kg/day based on decreased
pup weight
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870.4100 Chronic toxicity dogs NOAEL = 2 mg/kg/day
LOAEL = 20 mg/kg/day based on increased
bile duct hyperplasia in both males and
females, increased serum alkaline
phosphatase activity in both males and
females, increased relative and absolute
liver weights and decreased liver function
in females
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870.4200 Carcinogenicity mice NOAEL = 1.82 mg/kg/day for males and 17.4
mg/kg/day for females.
LOAEL 17.40 and 191.0 mg/kg/day for males
and females respectively, based on
increased absolute liver weights,
increased hepatocellular adenomas in
females, and increased hepatocellular
adenomas + carcinomas in females
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870.4300 Carcinogenicity rats NOAEL = 1 mg/kg/day
LOAEL = 8.7 mg/kg/day based on increased
incidence of follicular cell hyperplasia
and hypertrophy in thyroid in males. No
evidence of carcinogenicity
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870.5100 Gene mutation salmonella Not mutagenic, with or without activation
tested up to cytotocic levels.
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870.5100 Gene mutation mouse Not mutagenic, with or without activation
lymphoma tested up to cytotoxic levels.
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870.5100 Gene mutation in vitro Negative for micronucleus induction in bone
human cytogenetic assay marrow cells of males and females. Tested
up to cytotoxic levels.
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870.5100 Unscheduled DNA synthesis Negative for DNA repair tested up to
cytotoxic levels.
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870.7485 Metabolism and 79.1% recovered from feces, 12.9% from
pharmacokinetics urine within 72 hours and 45.4% recovered
as parent cpd, several metabolites
identified.
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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.
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 the
appropriate UF (RfD = NOAEL/UF). Where an additional safety factor is
retained due to concerns unique to the FQPA, 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 FQPA 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 is expressed as 1 x 10-6 or one in a million).
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 buprofezin used for human risk assessment is shown in the
following Table 2:

Table 2.--Summary of Toxicological Dose and Endpoints for Buprofezin for Use in Human Risk Assessment
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FQPA SF* and Level of
Exposure Scenario Dose Used in Risk Concern for Risk Study and Toxicological
Assessment, UF Assessment Effects
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Acute dietary (females 13-50 years of NOAEL = 200 mg/kg/day FQPA SF = 3x Developmental toxicity
age) UF = 100............... aPAD = acute RfD rat
Acute RfD = 2.0 mg/kg/ FQPA SF = LOAEL = 800 mg/kg/day
day. 0.67 mg/kg/day. based on skeletal
effects and decreased
body weight in
offspring.
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Acute dietary (general population N/A N/A No appropriate study
including infants and children) with a single-dose
endpoint. This risk
assessment is not
required.
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Chronic dietary (all populations) NOAEL= 1.0 mg/kg/day FQPA SF = 3x 2-Year chronic toxicity/
UF = 100............... cPAD = chronic RfD carcinogenicity in rat
Chronic RfD = 0.01 mg/ divide FQPA SF = 0.003 LOAEL = 8.7 mg/kg/day
kg/day. mg/kg/day. based on increased
incidence of
follicular cell
hyperplasia and
hypertrophy in the
thyroid of males.
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Intermediate-term dermal (1 week to Dermal NOAEL = 300 mg/ LOC for MOE = 100 24-Day dermal toxicity
several months) (residential) kg/day (Occupational) rat
LOAEL = 1,000 mg/kg/day
based on an increase
of focal necrosis with
an inflammatory
infiltrate in liver in
females
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Short-term inhalation (1 to 7 days) Inhalation (or oral) LOC for MOE = 100 Developmental toxicity
(residential) study (Occupational) rat
NOAEL= 200 mg/kg/day LOAEL = 800 mg/kg/day
(inhalation absorption based on skeletal
rate = 100%). effects and decreased
body weight in
offspring
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Intermediate-term inhalation (1 week Oral study NOAEL = 13 LOC for MOE = 100 90-day oral subchronic
to several months) (residential) mg/kg/day (inhalation (Occupational) study in rat
absorption rate = LOAEL = 68.6 mg/kg/day
100%) based on organ weight
changes and
microscopic findings
in liver and thyroid
(male and females) and
kidney (males only).
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Cancer (oral, dermal, inhalation) Suggestive evidence of N/A 2-Year carcinogenicity
carcinogenicity, but study in mice.
not sufficient to Liver tumors observed
assess human in female mice. The
carcinogenic potential Agency's Cancer
Assessment Review
Committee (CARC)
recommended that no
quantification of
cancer risk is
required.
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*The reference to the FQPA Safety Factor refers to any additional safety factor
retained due to concerns unique to the FQPA.

C. Exposure Assessment

1. Dietary exposure from food and feed uses. Tolerances have been
established (40 CFR 180.511) for the residues of buprofezin, in or on a
variety of raw agricultural commodities. Tolerances were corrected from
the petitioner's original request from the following commodities:
bananas at 0.1 ppm, citrus crop group, fruit, at 0.7 ppm, citrus oil at
26 ppm; citrus pulp, dried, at 2.5 ppm, and meat of cattle, goats,
hogs, horses, and sheep at 0.05 ppm. The petitioner in the case of
bananas, citrus and associated byproducts utilized the average residue
values, and the Agency utilized the highest sample concentration for
the purpose of evaluating the risk assessment. In addition, the Agency
determined upon evaluation of the submitted data, that a residue for
meat of cattle, goats, hogs, horses and sheep of 0.05 ppm was
unnecessary. Risk assessments were conducted by EPA to assess dietary
exposures from buprofezin 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 1 day or
single exposure. The Dietary Exposure Evaluation Model (DEEM\TM\ ver
7.075) analysis evaluated the individual food consumption as reported
by respondents in the USDA 1989-1992 nationwide Continuing Surveys of
Food Intake by Individuals (CSFII) and accumulated exposure to the
chemical for each commodity. The acute analysis assumed tolerance level
residues and 100% crop treated for all registered and proposed uses.
ii. Chronic exposure. In conducting this chronic dietary risk
assessment the DEEM\TM\ analysis evaluated the individual food
consumption as reported by respondents in the USDA 1989-1992 nationwide
CSFII and accumulated exposure to the chemical for each commodity. The
following assumptions were made for the chronic exposure assessments:
The chronic analysis incorporated average residues calculated from
field trial and processing studies and assumed 100% crop treated for
all commodities except tomatoes (40% crop treated assumed). The acute
and chronic dietary food exposure estimates to buprofezin, for all
population subgroups, were less than the Agency's level of concern
(greater than 100% aPAD and cPAD)
iii. Cancer. In accordance with the EPA Guidelines for Carcinogen
Risk Assessment (proposed July 1999), the Agency's Cancer Assessment
Review Committee has classified buprofezin as having "suggestive
evidence of carcinogenicity," but not sufficient to assess human
carcinogenic potential, and further recommended that no quantification
of cancer risk is required. Therefore, a cancer risk assessment is not
required.
iv. Anticipated residue and percent crop treated information.
Section 408(b)(2)(E) 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 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. As required by section 408(b)(2)(E), EPA will
issue a Data Call-In for information relating to anticipated residues
to be submitted no later than 5 years from the date of issuance of this
tolerance.
The Agency used percent crop treated (PCT) information as follows.
The Agency believes that the three conditions listed above have
been met. With respect to Condition 1, PCT estimates are derived from
Federal and private market survey data, which are reliable and have a
valid basis. EPA uses a weighted average PCT for chronic dietary
exposure estimates. This weighted average PCT figure is derived by
averaging State-level data for a period of up to 10 years, and
weighting for the more robust and recent data. A weighted average of
the PCT reasonably represents a person's dietary exposure over a
lifetime, and is unlikely to underestimate exposure to an individual
because of the fact that pesticide use patterns (both regionally and
nationally) tend to change continuously over time, such that an
individual is unlikely to be exposed to more than the average PCT over
a lifetime. For acute dietary exposure estimates, EPA uses an estimated
maximum PCT. The exposure estimates resulting from this approach
reasonably represent the highest levels to which an individual could be
exposed, and are unlikely to underestimate an individual's acute
dietary exposure. The Agency is reasonably certain that the percentage
of the food treated is not likely to be an underestimation. As to
Conditions 2 and 3, regional consumption information and consumption
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 buprofezin may
be applied in a particular area. All estimates assumed 100% crop
treated for all commodities except tomatoes (40% crop treated assumed
because Agency data indicates that actual application of buprofezin on
all tomatoes produced in the U.S. would be less than 40%).
2. Dietary exposure from drinking water. The Agency Metabolism
Assessment Review Committee has concluded that buprofezin was the only
residue of concern in drinking water (acute and chronic ground water
EECs of 0.09 ppb (SCI-GROW) and peak and 56-day average surface water
concentrations of 34 ppb and 17.7 ppb (17.7/3 = 5.9 ppb), respectively
(GENEEC; Tier 1)).
The Agency uses the Generic Estimated Environmental Concentration
(GENEEC) or the Pesticide Root Zone/Exposure Analysis Modeling System
(PRZM/EXAMS) to estimate pesticide concentrations in surface water and
SCI-GROW, which predicts pesticide concentrations in ground water. In
general, EPA will use GENEEC (a tier 1 model) before using PRZM/EXAMS
(a tier 2 model) for a screening-level assessment for surface water.
The GENEEC model is a subset of the PRZM/EXAMS model that uses a
specific high-end runoff scenario for pesticides. GENEEC incorporates a
farm pond scenario, while PRZM/EXAMS incorporate an index reservoir
environment in place of the previous pond scenario. The PRZM/EXAMS
model includes a percent crop area factor as an adjustment to account
for the maximum percent crop coverage within a watershed or drainage
basin.
None of these models include consideration of the impact processing
(mixing, dilution, or treatment) of 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 sorting out pesticides for
which it is highly unlikely that drinking water concentrations would
ever exceed human health levels of concern.
Since the models used are considered to be screening tools in the
risk assessment process, the Agency does not use estimated
environmental concentrations (EECs) from these models to quantify
drinking water exposure and risk as a %RfD or %PAD. Instead drinking
water levels of comparison (DWLOCs) are calculated and used as a point
of comparison against the model estimates of a pesticide's
concentration in water. DWLOCs are theoretical upper limits on a
pesticide's concentration in drinking water in light of total aggregate
exposure to a pesticide in food, and from residential uses. Since
DWLOCs address total aggregate exposure to buprofezin they are further
discussed in the aggregate risk sections below.
Based on the GENEEC and SCI-GROW models the EECs of buprofezin for
acute and chronic ground water estimated EECs of 0.09 ppb (SCI-GROW)
and peak and 56-day average surface water concentrations of 34 ppb and
17.7 ppb (17.7/3 = 5.9 ppb), respectively (GENEEC; Tier 1).
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).
Buprofezin is not registered for use on any sites that would result
in residential 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 buprofezin 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,
buprofezin 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 buprofezin 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 (62 FR 62961, November 26, 1997).

D. Safety Factor for Infants and Children

1. Safety factor for infants and children--i. In general. 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 on toxicity and exposure 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.
ii. Prenatal and postnatal sensitivity. It was concluded that
toxicity data provide no indication of increased susceptibility of rats
or rabbits following in utero exposure or of rats following prenatal/
postnatal exposure to buprofezin. In the prenatal developmental
toxicity study in rats, developmental effects were seen only in the
presence of severe maternal toxicity including deaths. No developmental
toxicity was seen at the highest dose tested in the prenatal
developmental toxicity study in rabbits. In the two-generation
reproduction study in rats, effects in the offspring were observed only
at treatment levels which resulted in evidence of parental toxicity
iii. Conclusion. The toxicology data base for buprofezin is
complete for FQPA assessment. The developmental toxicity studies in
rats and rabbits and the two-generation reproduction study in rats are
available and considered acceptable acute and subchronic neurotoxicity
studies are not required for buprofezin.
The Agency determined that an additional developmental
neurotoxicity study in rats is required based on the evidence of
thyroid toxicity following subchronic and chronic exposures to rats as
well as chronic exposures to dogs. In these studies, thyroid toxicity
was characterized as decreases in serum thyroxine levels and increased
thyroid weights in dogs and histopathological lesions in the subchronic
and chronic toxicity studies in rats. While the Agency recognized the
fact that thyroid toxicity was seen in the presence of hepatotoxicity,
there was concern that thyroid effects were seen in two species
following subchronic and chronic exposures.
The Agency concluded that the DNT study is needed to further
evaluate the hormonal responses associated with the developing fetal
nervous system. The Agency concluded that a safety factor is necessary
for buprofezin since there is a data gap for a developmental
neurotoxicity study in rats. This study is required due to the evidence
of thyroid toxicity observed following subchronic and chronic exposures
to rats and chronic exposure to dogs.
The safety factor was reduced to 3x because: (1) There is no
evidence of increased susceptibility to young rats or rabbits following
in utero exposure or following prenatal and/or postnatal exposure to
rats; (2) adequate actual data, surrogate data, and/or modeling outputs
are available to satisfactorily assess dietary (food and water)
exposure assessment; (3) and there are no registered residential uses
at the present time.
The FQPA safety factor for buprofezin is applicable to females 13-
50 years and to infants and children due uncertainty resulting from
data gap for the developmental neurotoxicity study in rats. This study
will characterize the potential for neurotoxic effects on fetal
development and may provide data that could be used in the toxicology
endpoint selection for dietary exposure risk assessments for these
population subgroups.

E. Aggregate Risks and Determination of Safety

To estimate total aggregate exposure to a pesticide from food,
drinking water, and residential uses, the Agency calculates DWLOCs
which are used as a point of comparison against the model estimates of
a pesticide's concentration in water (EECs). DWLOC values are not
regulatory standards for drinking water. DWLOCs are theoretical upper
limits on a pesticide's concentration in drinking water in light of
total aggregate exposure to a pesticide in food and residential uses.
In calculating a DWLOC, the Agency determines how much of the
acceptable exposure (i.e., the PAD) is available for exposure through
drinking water (e.g., allowable chronic water exposure (mg/kg/day) =
cPAD - (average food + residential exposure). This allowable exposure
through drinking water is used to calculate a DWLOC.
A DWLOC will vary depending on the toxic endpoint, drinking water
consumption, and body weights. Default body weights and consumption
values as used by the USEPA Office of Water are used to calculate
DWLOCs: 2L/70 kg (adult male), 2L/60 kg (adult female),
and 1L/10 kg (child). Default body weights and drinking water
consumption values vary on an individual basis. This variation will be
taken into account in more refined screening-level and quantitative
drinking water exposure assessments. Different populations will have
different DWLOCs. Generally, a DWLOC is calculated for each type of
risk assessment used: acute, short-term, intermediate-term, chronic,
and cancer.
When EECs for surface water and ground water are less than the
calculated DWLOCs, the Agency concludes with reasonable certainty that
exposures to the pesticide in drinking water (when considered along
with other sources of exposure for which the Agency has reliable data)
would not result in unacceptable levels of aggregate human health risk
at this time. Because the Agency considers the aggregate risk resulting
from multiple exposure pathways associated with a pesticide's uses,
levels of comparison in drinking water may vary as those uses change.
If new uses are added in the future, the Agency will reassess the
potential impacts of residues of the pesticide in drinking water as a
part of the aggregate risk assessment process.
1. Acute risk. To estimate acute aggregate exposure risk, the
Agency combined the high-end value from food and water and compared it
to the aPAD. Using the exposure assumptions discussed in this unit for
acute exposure, the acute dietary exposure from food to buprofezin will
occupy 4% of the aPAD for females 13 years and older (no endpoint was
identified for the general population including infants and children).
In addition, there is potential for acute dietary exposure to
buprofezin in drinking water. After calculating DWLOCs and comparing
them to the EECs for surface and ground water, EPA does not expect the
aggregate exposure to exceed 100% of the aPAD, as shown in the
following Table 3:

Table 3.--Aggregate Risk Assessment for Acute Exposure to buprofezin

--------------------------------------------------------------------------------------------
Surface Water EEC Ground Water EEC
Population Subgroup aPAD (mg/kg) %aPAD (Food) (ppb) (ppb) Acute DWLOC (ppb)
--------------------------------------------------------------------------------------------
Females (13-50) 0.67 4% 34 0.09 1.9 x 104
--------------------------------------------------------------------------------------------

2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
buprofezin from food will utilize 73% of the cPAD for all population
subgroups. There are no residential uses for buprofezin that result in
chronic residential exposure to buprofezin. In addition, there is
potential for chronic dietary exposure to buprofezin in drinking water.
After calculating DWLOCs and comparing them to the EECs for surface and
ground water, EPA does not expect the aggregate exposure to exceed 100%
of the cPAD, as shown in the following Table 4:

Table 4.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to buprofezin

------------------------------------------------------------------------------------------------
Food Surface Ground
Population Subgroup cPAD mg/kg/ Exposure mg/ Water EEC Water EEC Chronic
day kg/day (ppb) (ppb) DWLOC (ppb)
------------------------------------------------------------------------------------------------
U.S. population (all) 0.0033 0.001226 5.9 0.09 73
------------------------------------------------------------------------------------------------
All Infants (less than 1 year) 0.0033 0.000968 5.9 0.09 23
------------------------------------------------------------------------------------------------
Children (1-6 years) 0.0033 0.002385 5.9 0.09 9
------------------------------------------------------------------------------------------------
Children (7-12 years) 0.0033 0.001622 5.9 0.09 17
------------------------------------------------------------------------------------------------
Females (13-50) 0.0033 0.001084 5.9 0.09 66
------------------------------------------------------------------------------------------------
Males (13-19 years) 0.0033 0.001050 5.9 0.09 79
------------------------------------------------------------------------------------------------
Males (20+ years) 0.0033 0.000999 5.9 0.09 81
------------------------------------------------------------------------------------------------
Seniors (55+) 0.0033 0.001060 5.9 0.09 78
------------------------------------------------------------------------------------------------

3. Short-term risk. Short-term aggregate exposure takes into
account residential exposure plus chronic exposure to food and water
(considered to be a background exposure level). Buprofezin is not
registered for use on any sites that would result in residential
exposure. Therefore, the aggregate risk is the sum of the risk from
food and water, which do not exceed the Agency's level of concern.
4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account residential exposure plus chronic exposure to food
and water (considered to be a background exposure level). Buprofezin is
not registered for use on any sites that would result in residential
exposure. Therefore, the aggregate risk is the sum of the risk from
food and water, which do not exceed the Agency's level of concern.
5. Aggregate cancer risk for U.S. population. In accordance with
the EPA Guidelines for Carcinogen Risk Assessment (proposed July 1999),
the Agency's Cancer Assessment Review Committee has classified
buprofezin as having suggestive evidence of carcinogenicity, but not
sufficient to assess human carcinogenic potential, and further
recommended that no quantification of cancer risk is required.
Therefore, a cancer risk assessment is not required.
6. 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 to infants and children from aggregate
exposure to buprofezin residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

1. Residue analytical methods-plants. The petitioner proposed
method BF/10/97 for enforcement of the almond, banana, citrus, cotton,
and grape tolerances. Adequate radiovalidation and independent
laboratory validation (ILV) have been received and the method was
forwarded to the Analytical Chemistry Laboratory (ACL) for petition
method validation (PMV). The petitioner will be required to make any
modifications or revision to the proposed enforcement method resulting
from PMV. The petitioner is requested to submit a confirmatory method
and an interference study. If the petitioner proposes a confirmatory
method which employs a mass spectrum detector (MS), then an
interference study is not necessary (chromatograms and spectra of
fortified samples should be submitted; structurally significant ions
should be chosen with a m/z 91 and intensity 3x noise at the LOQ for
the primary method).
2. Residue analytical methods-livestock. The petitioner proposed
method BF/11/97 for enforcement of livestock tolerances. Adequate ILV
has been received and the method was forwarded to the ACL for PMV
(D271333, T. Bloem, 21-Dec-2000). The petitioner will be required to
make any modifications or revision to the proposed enforcement method
resulting from the PMV. The petitioner is also required to submit a
radiovalidation study.
3. Multiresidue method. The petitioner submitted data concerning
the behavior of buprofezin through FDA multiresidue testing protocols
C-F. This information has been forwarded to FDA for inclusion in PAM I.

B. International Residue Limits

Codex has a maximum residue limit (MRL) for buprofezin in/on tomato
(1 ppm) and oranges (0.5 ppm). Mexico has a MRL for buprofezin in/on
cottonseed (0.05 ppm). Canada does not have any MRLs for the proposed
crops. Since the orange and cottonseed MRLs are less than the
tolerances determined appropriate by the Agency, harmonization is not
possible. Since the tomato MRL is 2x the tolerance determined
appropriate by the Agency, harmonization is not possible.

C. Conditions

Conditions for continued registration are as follows: A
developmental neurotoxicity study in rats (OPPTS 870.6300) guideline
requirement (40 CFR part 158) for Food/Feed Use due to possible
endocrine disruptor effects, a revised Section B, a revised Section F,
Plant Enforcement Method (BF/10/97) - Confirmatory Method, Interference
Study, and successful Agency Validation, Plant Enforcement Method (BF/
02/96) - Confirmatory Method and Interference Study, Livestock
Enforcement Method - successful Agency Validation and Radioavalidation,
Storage Stability Data, validation of frozen storage intervals,
petition method validation, an interference study, Additional almond,
banana, citrus, cotton, and tomato field trial data, and a citrus
processing study.

V. Conclusion

Therefore, the tolerance is established for residues of buprofezin
(2-tert-butylimino-3-isopropyl-5-phenyl-1,3,5-thiadiazinan-4-one), in
or on almond; banana; citrus; citrus, oil; citrus, dried pulp; grape;
grape, raisin; milk; fat (cattle, goats, hogs, horses, sheep); meat
byproducts (cattle, goats, hogs, horses, sheep); liver (cattle, goats,
hogs, horses, sheep); almond, hulls; cotton, undelinted seed; cotton,
gin byproducts and tomato at 0.05, 0.20, 2.0, 60, 6.0, 0.40, 0.60,
0.01, 0.05, 0.05, 0.05, 0.70, 0.40, 15, 0.40 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-301159 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 November
5, 2001.
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, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460. You may also deliver your request to the Office
of the Hearing Clerk in Rm. C400, 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, 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, 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-301159, 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.
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 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 (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 prior consultation as specified by
Executive Order 13084, entitled Consultation and Coordination with
Indian Tribal Governments (63 FR 27655, May 19, 1998); special
considerations as required by Executive Order 12898, entitled Federal
Actions to Address Environmental Justice in Minority Populations and
Low-Income Populations (59 FR 7629, February 16, 1994); or require 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 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(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 FFDCA section 408(n)(4).

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 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: August 21, 2001.
Donald R. Stubbs,
Acting Director, Registration Division, 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), 346(a) and 371.

2. Section 180.511 is amended by alphabetically adding the
following commodities to the table in paragraph (a) and by removing and
reserving paragraph (b) to read as follows:

Sec. 180.511 Buprofezin; tolerances for residues.

(a) * * *

------------------------------------------------------------------------
Expiration/
Commodity Parts per million Revocation Date
------------------------------------------------------------------------
Almonds, nutmeat 0.05 none
Almond, hulls 0.70 12/31/05
Banana 0.20 none
Cattle, fat 0.05 none
Cattle, mbyp 0.05 none
Cattle, liver 0.05 none
Citrus fruit 2.0 none
Citrus, oil 60 none
Citrus, dried pulp 6.0 none
Cotton, gin byproducts 15 12/31/05
Cotton, undelinted seed 0.40 12/31/05
Goats, fat 0.05 none
Goats, mbyp 0.05 none
Goats, liver 0.05 none
Grape 0.40 none
Grape, raisin 0.60 none
Hogs, fat 0.05 none
Hogs, mbyp 0.05 none
Hogs, liver 0.05 none
Horses, fat 0.05 none
Horses, mbyp 0.05 none
Horses, liver 0.05 none
* * * * * * *
Milk 0.01 none
Sheep, fat 0.05 none
Sheep, mbyp 0.05 none
Sheep, liver 0.05 none
Tomato 0.40 12/31/05
* * * * * * *
------------------------------------------------------------------------

* * * * *
(b) Section 18 emergency exemption. [Reserved]

[FR Doc. 01-22281 Filed 9-4-01; 8:45 am]