Pesticides; tolerances in food, animal feeds, and raw agricultural commodities: Pryriproxyfen,

[Federal Register: June 5, 2001 (Volume 66, Number 108)]

[Rules and Regulations]

[Page 30065-30073]

From the Federal Register Online via GPO Access [wais.access.gpo.gov]

[DOCID:fr05jn01-6]

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.

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: jamerson.hoyt@epa.gov.

SUPPLEMENTARY INFORMATION:

1. General Information

   1. 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.

   2. 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.

2. 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).

3. 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.

   1. 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 F1generation and liver and kidney histopathology in F1males. 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

   2. 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 10-6or 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.

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      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.

   3. 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).

   4. 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.

   5. 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 (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 (01-14085Filed6-4-01; 8:45 am] BILLING CODE 6560-50-S