[Federal Register Volume 66, Number 108 (Tuesday, June 5, 2001)]
[Rules and Regulations]
[Pages 30065-30073]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-14085]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-301131; FRL-6782-5]
RIN 2070-AB78


Pyriproxyfen; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes a tolerance for residues of 
pyriproxyfen in or on pistachio. The Interregional Research Project 
Number 4 (IR-4) requested this tolerance under the Federal Food, Drug, 
and Cosmetic Act, as amended by the Food Quality Protection Act of 
1996.

DATES: This regulation is effective June 5, 2001. Objections and 
requests for hearings, identified by docket control number OPP-301131, 
must be received by EPA on or before August 6, 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-301131 in the 
subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Hoyt Jamerson, Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW.,Washington, DC 20460; 
telephone number: (703) 308-9368; and e-mail address: 
[email protected].

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

[[Page 30066]]

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/. 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.html, a beta site currently 
under development. To access the OPPTS Harmonized Guidelines referenced 
in this document, go directly to the guidelines at http://www.epa.gov/opptsfrs/home/guidelin.htm.
    2. In person. The Agency has established an official record for 
this action under docket control number OPP-301131. 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 April 4, 2001 (66 FR 17883) (FRL-6772-
4), 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 0E6081) for tolerance by IR-4, 
Technology Center of New Jersey, Rutgers, The State University of New 
Jersey, 681 U.S. Highway #1 South, North Brunswick, NJ 08902-3390. This 
notice included a summary of the petition prepared by Valent U.S.A. 
Corporation, 1333 North California Blvd., P.O. Box 8025, Walnut Creek, 
CA 94596-8025, the registrant. There were no comments received in 
response to the notice of filing.
    The petition requested that 40 CFR 180.510 be amended by 
establishing a tolerance for residues of the insecticide pyriproxyfen, 
2-[1-methyl-2-(4-phenoxyphenoxy)ethoxypyridine, in or on pistachio at 
0.02 part per million (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 pyriproxyfen on pistachio at 
0.2 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 pyriproxyfen 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
----------------------------------------------------------------------------------------------------------------
              Guideline No.                        Study Type                           Results
----------------------------------------------------------------------------------------------------------------
870.3100                                  Subchronic feeding in rats   NOAEL = 23.49 mg/kg/day in males 27.68 mg/
                                           (13 weeks)                   kg/day in females
                                                                       LOAEL = 117.79 milligram/kilogram/day (mg/
                                                                        kg/day) in males and 141.28 mg/kg/day in
                                                                        females based on higher mean total
                                                                        cholesterol and phospholipids; decreased
                                                                        mean red blood cells, hematocrit and
                                                                        hemoglobin counts and increased liver
                                                                        weight.
----------------------------------------------------------------------------------------------------------------
870.3150                                  Subchronic oral toxicity in  NOAEL = 100 mg/kg/day
                                           dogs (13 weeks)             LOAEL = 300 mg/kg/day based on increased
                                                                        absolute and relative liver weight in
                                                                        males and hepatocellular hypertrophy in
                                                                        females. These findings were also
                                                                        observed at 1,000 mg/kg/day and may
                                                                        represent adaptive changes at both 300
                                                                        mg/kg/day and the limit dose of 1,000 mg/
                                                                        kg/day.
----------------------------------------------------------------------------------------------------------------
870.3200                                  21-Day dermal toxicity       NOAEL = >1,000 mg/kg/day
                                           (rat)                       There was no dermal or systemic toxicity
                                                                        at the 1,000 mg/kg/day dose, highest
                                                                        dose tested (HDT).
----------------------------------------------------------------------------------------------------------------

[[Page 30067]]

 
870.3700a                                 Prenatal developmental       Maternal NOAEL = 100 mg/kg/day
                                           (rat)                       LOAEL = 300 mg/kg/day based on increased
                                                                        incidences in mortality and clinical
                                                                        signs at 1,000 mg/kg/day with decreases
                                                                        in food consumption, body weight, and
                                                                        body weight gain together with increases
                                                                        in water consumption at 300 and 1,000 mg/
                                                                        kg/day.
                                                                       Developmental NOAEL = 300 mg/kg/day
                                                                       LOAEL = 1,000 mg/kg/day based on
                                                                        increased incidences of skeletal
                                                                        variations and unspecified visceral
                                                                        variations at 1,000 mg/kg/day.
----------------------------------------------------------------------------------------------------------------
870.3700b                                 Prenatal developmental       Maternal NOAEL = 100 mg/kg/day
                                           (rabbit)                    LOAEL = 300 mg/kg/day based on based on
                                                                        premature delivery/abortions, soft
                                                                        stools, emaciation, decreased activity
                                                                        and bradypnea.
                                                                       Developmental NOAEL = 300 mg/kg/day
                                                                       LOAEL = 1,000 mg/kg/day. There were no
                                                                        effects observed in the 4 litters
                                                                        examined.
----------------------------------------------------------------------------------------------------------------
870.3800                                  Reproduction and fertility   Parental/systemic NOAEL = 76 mg/kg/day in
                                           effects (rat)                males and 87 mg/kg/day in females
                                                                       LOAEL = 386 mg/kg/day and males 442mg/kg/
                                                                        day in females based on decreased body
                                                                        weight, weight gain and food consumption
                                                                        in both sexes and both generations.
                                                                        Increased liver weight in both sexes of
                                                                        the F1 generation and liver and kidney
                                                                        histopathology in F1 males.
                                                                       Reproductive NOAEL = 386 mg/kg/day in
                                                                        males and 442 mg/kg/day in females
                                                                        (highest dose tested).
                                                                       Offspring NOAEL = 97 mg/kg/day in males
                                                                        and 105 mg/kg/day in females
                                                                       LOAEL = 519 mg/kg/day in males and 554 mg/
                                                                        kg/day in females based on decreased pup
                                                                        body weight on lactation.
----------------------------------------------------------------------------------------------------------------
870.3800                                  Perinatal and postnatal      Maternal NOAEL: 100 mg/kg/day
                                           study of pyriproxyfen       Maternal LOAEL: 300 mg/kg/day based on
                                           orally administered to       increased clinical signs, decreased body
                                           rats                         weight gains, and decreased food
                                                                        consumption
                                                                       Pup NOAEL: 100 mg/kg/day
                                                                       Pup LOAEL: 300 mg/kg/day based on
                                                                        decreased body weight and increased
                                                                        incidence of dilation of the renal
                                                                        pelvis. At 500 mg/kg/day, there was an
                                                                        increase in pup mortality during
                                                                        lactation
                                                                       Pup Reproductive, Developmental, and
                                                                        Learning
                                                                       NOAEL: 500 mg/kg/day
                                                                       LOAEL: 500 mg/kg/day
----------------------------------------------------------------------------------------------------------------
870.3800                                  Non-guideline study of rats  Parental NOAEL = 100 mg/kg/day
                                           orally exposed prior to     Parental LOAEL = 300 mg/kg/day based on
                                           and in the early stages of   increased clinical signs, decreased body
                                           pregnancy                    weight gains, and increased water
                                                                        consumption in both sexes, and increased
                                                                        food consumption, changes in organ
                                                                        weights, and gross pathological findings
                                                                        in the males only.
                                                                       Developmental NOAEL = 1,000 mg/kg/day
                                                                       Developmental LOAEL = 1,000 mg/kg/day
----------------------------------------------------------------------------------------------------------------
870.4300                                  Chronic toxicity/            NOAEL = 35.1 mg/kg/day (females)
                                           oncogenicity (rat)          LOAEL = 182.7 mg/kg/day (females) based
                                                                        on decrease in body weight gain in
                                                                        females at 182.70 mg/kg/day. There was
                                                                        no evidence of carcinogenic response.
----------------------------------------------------------------------------------------------------------------
870.4100                                  1-Year chronic feeding       NOAEL = 100 mg/kg/day
                                           (dog)                       LOAEL = 300 mg/kg/day based on decreased
                                                                        weight gain, increased absolute and
                                                                        relative liver weight, mild anemia,
                                                                        increased cholesterol and triglycerides
                                                                        in both sexes and slight anemia in
                                                                        males.
----------------------------------------------------------------------------------------------------------------
870.4200                                  Carcinogenicity mice         NOAEL = 84 mg/kg/day in males and 109 mg/
                                                                        kg/day in females
                                                                       LOAEL = 320 mg/kg/day in males and 547 mg/
                                                                        kg/day in females based on renal lesions
                                                                        in both sexes. No statistically
                                                                        significant increase in tumor incidence
                                                                        relative to controls were observed in
                                                                        either sex at any dose up to the highest
                                                                        dose tested.
----------------------------------------------------------------------------------------------------------------
870.5100                                  Gene Mutation Assay (Ames    Negative for induction of gene mutation
                                           Test) Reverse Mutation       measured as the reversion to histidine
                                                                        protrophy of 5 S. typhimurium strains
                                                                        and E. coli WP2 uvra at doses from 10 to
                                                                        5,000 g/plated with and withour
                                                                        S-9 activation.
----------------------------------------------------------------------------------------------------------------
870.5300                                  Gene Mutation                Negative for induction of gene mutation
                                                                        in Chinese hamster V79 cells with and
                                                                        without metabolic activation up to
                                                                        cytotoxic doses.
----------------------------------------------------------------------------------------------------------------

[[Page 30068]]

 
870.5380                                  Structural                   Nonclastogenic in Chinese hamster ovary
                                           ChromosomalAbberation In     cells both with and without S-9
                                           vivo                         activation up to cytotoxic doses.
----------------------------------------------------------------------------------------------------------------
870.5550                                  Unscheduled DNA Synthesis    Did not induce an increase in unscheduled
                                                                        DNA synthesis both with and without
                                                                        activation in HeLa cells exposed up to
                                                                        insoluble doses ranging to 6.4 g/mL without activation and 51.2
                                                                        g/mL with activation.
----------------------------------------------------------------------------------------------------------------
870.7485                                  Metabolism                   Rats were orally dosed with 14C-labeled
                                                                        pyriproxyfen at 2 or 1,000 mg/kg and at
                                                                        repeated oral doses 14 daily doses of
                                                                        unlabeled pyriproxyfen at 2 mg/kg
                                                                        followed by administration of a single
                                                                        oral dose of labeled pyriproxyfen at 2
                                                                        mg/kg. Most radioactivity was excreted
                                                                        in the feces 81-92% and urine 5-12% over
                                                                        a 7 day collection period. Expired air
                                                                        was not detected. Tissue radioactivity
                                                                        levels were very low less than 0.3%
                                                                        except for fat. Examination of urine,
                                                                        feces, liver, kidney, bile and blood
                                                                        metabolites yielded numerous > 20
                                                                        identified metabolites when compared to
                                                                        synthetic standards. The major
                                                                        biotransformation reactions of
                                                                        pyriproxyfen include: 1. Oxidation of
                                                                        the 4' - position of the terminal phenyl
                                                                        group; 2. Oxidation at the 5' - position
                                                                        of pyridine; 3. Cleavage of the ether
                                                                        linkage and conjugation of the resultant
                                                                        phenols with sulfuric acid.
----------------------------------------------------------------------------------------------------------------
870.7600                                  Dermal penetration
----------------------------------------------------------------------------------------------------------------

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 pyriproxyfen used for human risk assessment is shown in 
the following Table 2:

    Table 2.-- Summary of Toxicological Dose and Endpoints for pyriproxyfen for Use in Human 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 all populations          Not applicable           Not applicable           No effects that could
                                                                                          be attributed to a
                                                                                          single exposure were
                                                                                          observed in oral
                                                                                          toxicity studies.
----------------------------------------------------------------------------------------------------------------
Chronic dietary all populations        NOAEL= 35.1 mg/kg/day    FQPA SF = 1X             2-Year chronic feeding
                                       UF = 100...............  cPAD = chronic RfD        study in rats
                                       Chronic RfD = 0.35 mg/    FQPA SF.        LOAEL = 182.7 mg/kg/day
                                        kg/day.                 =0.35 mg/kg/day........   based on a decrease in
                                                                                          body weight gains in
                                                                                          females.
----------------------------------------------------------------------------------------------------------------

[[Page 30069]]

 
Short-term dermal and inhalation (1    Not applicable           Not applicable           21-Day dermal toxicity
 to 7 days) (residential)              Absorption rate = not                              study lack of dermal
                                        more than 10%.                                    or systemic toxicity
                                                                                          at the limit-dose of
                                                                                          1,000 mg/kg/day.
----------------------------------------------------------------------------------------------------------------
Intermediate-term dermal and           Not applicable           Not applicable           21-Day dermal toxicity
 inhalation (1 week to several         Absorption rate = not                              study
 months) (residential)                  more than 10%.                                   Lack of dermal or
                                                                                          systemic toxicity at
                                                                                          the limit-dose of
                                                                                          1,000 mg/kg/day.
----------------------------------------------------------------------------------------------------------------
Long-term dermal and inhalation        35.1 mg/kg/day           LOC for MOE = 100        Chronic toxicity/
 (several months to lifetime)                                   (residential)..........   carcinogenicity in
(residential)........................                                                     rats
                                                                                         LOAEL = 182.7 mg/kg/day
                                                                                          based on decreased
                                                                                          weight gain in female
                                                                                          rats.
----------------------------------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation)      ``Group E'' human        Not applicable           There is no evidence of
                                        carcinogen                                        carcinogenic
                                                                                          potential.
----------------------------------------------------------------------------------------------------------------
*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 180.510) for the combined residues of pyriproxyfen, 
in or on a variety of raw agricultural commodities. Permanent 
tolerances are established under 40 CFR 180.510(a) for residues of 
pyriproxyfen in/on the following commodities: pome fruits (crop group 
11) (0.2 ppm), citrus fruits (crop group 10) (0.3 ppm), fruiting 
vegetables (except cucurbits) (crop group 8) (0.2 ppm), tree nuts (crop 
group 14) (0.02 ppm), cotton seed (0.05 ppm), cotton gin byproducts 
(2.0 ppm), almond hulls (2.0 ppm), citrus oil (20 ppm), and citrus 
pulp, dried (2.0 ppm). Tolerances are also proposed by McLaughlin 
Gormley King Company for residues of pyriproxyfen in/on all food 
commodities at 0.10 ppm from use of the pesticide in food handling 
establishments. Risk assessments were conducted by EPA to assess 
dietary exposures from pyriproxyfen 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. An acute dose and endpoint were not selected for any 
population subgroup because no effects that could be attributed to a 
single exposure were observed in oral toxicity studies. Therefore, an 
acute exposure assessment was not conducted.
    ii. Chronic exposure. In conducting this chronic dietary risk 
assessment the Dietary Exposure Evaluation Model (DEEM) 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 following assumptions were made for the chronic exposure 
assessments: The chronic dietary exposure analysis for pyriproxyfen 
assumed tolerance level residues and 100% crop treated for all 
commodities with established or proposed tolerances.
    iii. Cancer. A cancer dietary exposure assessment was not performed 
since there was no evidence of carcinogenicity in studies conducted 
with rats and mice.
    2. Dietary exposure from drinking water. The Agency lacks 
sufficient monitoring exposure data to complete a comprehensive dietary 
exposure analysis and risk assessment for pyriproxyfen in drinking 
water. Because the Agency does not have comprehensive monitoring data, 
drinking water concentration estimates are made by reliance on 
simulation or modeling taking into account data on the physical 
characteristics of pyriproxyfen.
    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 
Screening Concentrations in Ground Water (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 pyriproxyfen they are 
further discussed in the aggregate risk sections below.
    Based on the PRZM/EXAMS and SCI-GROW models, the EECs of 
pyriproxyfen for acute exposures are estimated to be 0.46 parts per 
billion (ppb) for surface water and 0.006 ppb for ground water. The 
EECs for chronic

[[Page 30070]]

exposures are estimated to be 0.11 ppb for surface water and 0.006 ppb 
for ground water.
    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).
    Pyriproxyfen is currently registered for use on residential non-
dietary sites. Pyriproxyfen is the active ingredient in many registered 
residential (indoor, nonfood) products for flea and tick control. 
Formulations include foggers, aerosol sprays, emulsifiable concentrates 
and impregnated materials (pet collars). Pyriproxyfen residues from 
residential exposure to pet collars was estimated using the following 
assumptions: an application rate of 0.58 mg ai/day (product label), 
average body weight for a 1 to 6-year old child of 10 kg, the active 
ingredient dissipates uniformly through 365 days (the label instructs 
to change the collar once a year), and 1% of the active ingredient is 
available for dermal and inhalation exposure per day (assumption from 
Draft HED Standard Operating Procedures (SOPs) for Residential Exposure 
Assessments, December 18, 1997). The assessment also assumes an 
absorption rate of 100%. This is a conservative assumption since the 
dermal absorption was estimated to be 10%.
    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 pyriproxyfen 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, 
pyriproxyfen 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 pyriproxyfen 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. There is no indication of 
increased susceptibility of rats or rabbit fetuses to in utero and/or 
postnatal exposure in the developmental and reproductive toxicity 
studies.
    iii. Conclusion. There is a complete toxicity data base for 
pyriproxyfen and exposure data are complete or are estimated based on 
data that reasonably accounts for potential exposures. EPA determined 
that the 10X safety factor to protect infants and children should be 
removed (reduced to 1X). The FQPA factor is removed because: (1) The 
toxicology data base is complete; (2) there is no indication of 
increased susceptibility of rats or rabbit fetuses to in utero and/or 
postnatal exposure in the developmental and reproductive toxicity 
studies; (3) a developmental neurotoxicity study is not required; (4) 
dietary (food) exposure estimates are unrefined (assuming tolerance 
level residues and 100% crop treated) and likely result in an 
overestimate of the actual dietary exposure; (5) the models are used 
for ground and surface source drinking water exposure assessments 
result in estimates that are upper-bound concentrations; and (6) the 
Draft Standard Operating Procedures for Residential Exposure 
Assessments have been used as the basis for all calculations which 
normally rely on one or more upper-percentile assumptions and are 
considered to be protective.

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, OPP concludes with reasonable certainty that 
exposures to the pesticide in drinking water (when considered along 
with other sources of exposure for which OPP has reliable data) would 
not result in unacceptable levels of aggregate human health risk at 
this time. Because OPP 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, OPP 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. An acute dietary dose and endpoint was not 
identified. Thus the risk from acute aggregate exposure is considered 
to be negligible.
    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that exposure to 
pyriproxyfen from food will utilize 0.9% of the cPAD for the U.S. 
population, 1.6 % of the cPAD for all infants (< year) and 2.6% of the 
cPAD for children (1-6 years). With the exception of the pet collar 
uses, residential uses of pyriproxyfen result in short-term, 
intermittent exposures. Chronic residential postapplication risk

[[Page 30071]]

assessments were conducted to estimate the potential risk from the pet 
collar uses. The estimated chronic term MOE is 61,000 for children and 
430,000 for adults. The risk estimates indicate that potential risks 
from pet collar use do not exceed EPA level of concern (MOEs> 100). In 
addition, there is potential for chronic dietary exposure to 
pyriproxyfen 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 3:

                                  Table 3.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Pyriproxyfen
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                 Surface Water EEC   Ground Water EEC    Chronic DWLOC
                   Population Subgroup                       cPAD mg/kg/day      %cPAD (Food)          (ppb)              (ppb)              (ppb)
--------------------------------------------------------------------------------------------------------------------------------------------------------
U.S. Population                                                         0.35               0.9%               0.11              0.006             12,000
--------------------------------------------------------------------------------------------------------------------------------------------------------
All Infants (<1 year)                                                   0.35               1.6%               0.11              0.006              3,400
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children (1-6 years)                                                    0.35               2.6%               0.11              0.006              3,400
--------------------------------------------------------------------------------------------------------------------------------------------------------
Females (13-50 years)                                                   0.35               0.7%               0.11              0.006             10,000
--------------------------------------------------------------------------------------------------------------------------------------------------------

    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). Though residential 
exposure could occur with the use of pyriproxyfen, no toxicological 
effects have been identified for short-term toxicity. 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. Aggregate cancer risk for U.S. population. Pyriproxyfen is 
classified as Group E for human carcinogenicity; not carcinogenic in 
animal studies in two species.
    5. 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 pyriproxyfen residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    The gas-chromotography/nitrogen-phosphorous specific flame 
ionization detector (NPD) and high-pressure liquid chromotography/
fluorescence (FLD) method RM-33N-2 is adequate for collecting data on 
residues of pyriproxyfen in/on nutmeat. Adequate method validation data 
have been submitted for this method and EPA has successfully validated 
the analytical method for analysis of nutmeat. The limit of 
quantitation (LOQ) is 0.02 ppm for residues of pyriproxyfen in/on 
nutmeat.
    The method may be requested from: Calvin Furlow, PIRIB, IRSD 
(7502C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: 
(703) 305-5229; e-mail address: [email protected].

B. International Residue Limits

    There are no CODEX, Canadian, or Mexican tolerances for 
pyriproxyfen residues in/on pistachios. Therefore, international 
harmonization is not an issue at this time.

V. Conclusion

    Therefore, the tolerance is established for residues of 
pyriproxyfen in or on pistachio at 0.02 ppm.

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-301131 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 August 6, 
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

[[Page 30072]]

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 [email protected], 
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-301131, 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: [email protected]. 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). 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 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). 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. 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).

[[Page 30073]]

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.


    Dated: May 17, 2001.

James Jones,

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 180.510 is amended by revising the introductory text in 
paragraph (a)(1) and alphabetically adding the commodity ``pistachio'' 
to the table to read as follows:


Sec. 180.510  Pyriproxyfen; tolerances for residues.

    (a) General. (1) Tolerances are established for residues of the 
insecticide pyriproxyfen 2-[1-methyl-2-(4-phenoxyphenoxy)ethoxypyridine 
in or on the following food commodities:

----------------------------------------------------------------------------------------------------------------
                            Commodity                                            Parts per million
----------------------------------------------------------------------------------------------------------------
                             *          *          *          *          *
Pistachio........................................................                                           0.02
                            *          *            *          *          *
----------------------------------------------------------------------------------------------------------------

* * * * *

[FR Doc. 01-14085 Filed 6-4-01; 8:45 am]
BILLING CODE 6560-50-S