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CFR Citation: 40 CFR Part 180

RIN ID: RIN 2070-AB78]

OPP ID: [OPP-301064; FRL-6747-8]

NOTICE: RULES

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

DOCUMENT ACTION: Final rule.

SUBJECT CATEGORY: Indoxacarb; Pesticide Tolerance

DATES: This regulation is effective September 29, 2000. Objections and requests for hearings, identified by docket control number OPP301064, must be received by EPA on or before November 28, 2000.

DOCUMENT SUMMARY: This regulation establishes permanent tolerances for the combined residues of Indoxacarb, [(S)methyl 7chloro2,5dihydro2 [[(methoxycarbonyl)[4(trifluoromethoxy)phenyl]
amino]carbonyl]indeno[1,2e][1,3,4] oxadiazine4a(3H) carboxylate] and its Renantiomer [(R)methyl 7chloro2,5dihydro2
[[(methoxycarbonyl)[4(trifluoromethoxy) phenyl]amino] carbonyl]indeno [1,2e][1,3,4] oxadiazine4a(3H) carboxylate] in a 75:25 mixture (DPX MP062), respectively, in or on the raw agricultural commodities as follows: apples, pears, Brassica (head and stem subgroup), cotton, leaf lettuce, head lettuce, fruiting vegetable group, sweet corn, milk, and the meat, meat byproducts and fat of cattle, goats, horses, hogs and sheep. E. I. du Pont de Nemours and Company requested these tolerances under the Federal Food, Drug, and Cosmetic Act, as amended by the Food Quality Protection Act of 1996.

SUMMARY: Indoxacarb,

SUPPLEMENTAL 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 Potentially Affected Entities Industry 111 Crop production 112 Animal production 311 Food manufacturing 32532 Pesticide manufacturing

This listing is not intended to be exhaustive, but rather provides a guide for readers regarding entities likely to be affected by this action. Other types of entities not listed in the table could also be affected. The North American Industrial Classification System (NAICS) codes have been provided to assist you and others in determining whether or not this action might apply to certain entities. If you have questions regarding the applicability of this action to a particular entity, consult the person listed under FOR FURTHER INFORMATION CONTACT.
B. How Can I Get Additional Information, Including Copies of this Document and Other Related Documents?

1. Electronically.You may obtain electronic copies of this document, and certain other related documents that might be available electronically, from the EPA Internet Home Page at http://www.epa.gov/. To access this document, on the Home Page select ``Laws and Regulations,'' ``Regulations and Proposed Rules,'' and then look up the entry for this document under the ``Federal RegisterEnvironmental Documents.'' You can also go directly to the Federal Register listings at http://www.epa.gov/fedrgstr/. To access the OPPTS Harmonized Guidelines referenced in this document, go directly to the guidelines at http://www.epa.gov/opptsfrs/home/guidelin.htm.

2. In person. The Agency has established an official record for this action under docket control number OPP301064. 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) 3055805. II. Background and Statutory Findings

In the Federal Register of April 16, 1998 (63 FR 1891218919) (FRL 57828), 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 104170) announcing the filing of a pesticide petition (PP) 8F4948, for tolerance by E. I. du Pont de Nemours and Company, P.O. Box 80038, Wilmington, DE 198800038. This notice included a summary of the petition prepared by DuPont, the registrant. There were three comments in response to the Notice of Filing from members of the cotton industry. They expressed concern for the use of terminology associated with cotton in the Notice of Filing. These cotton terminology comments were forwarded within the Agency to the evaluators of the cotton portion of the submission which ultimately did not impact the interpretation of the submission.

The petition (8F4948) requested that 40 CFR 180.564 be amended by establishing permanent tolerances for residues of the insecticide DPX MP062 (75:25 enantiomeric mixture of indoxacarb and its Renantiomer), [R,S)methyl 7chloro2,5dihydro2[[(methoxycarbonyl)[4
(trifluoromethoxy)phenyl] amino]carbonyl] indeno[1,2e][1,3,4] oxadiazine4a(3H)carboxylate] in/on the raw agricultural commodities as follows: pome fruit at 2.0 parts per million (ppm), apple pomace at 6.0 ppm, Brassicas, head and stem at 10.0 ppm, cottonseed at 3.0 ppm, cotton gin trash at 15.0 ppm, leaf lettuce at 20.0 ppm, head lettuce at 7.0 ppm, fruiting vegetables at 0.70 ppm, sweet corn kernel at 0.02 ppm, sweet corn forage at 20.0 ppm, and sweet corn stover at 25.0 ppm, meat 0.02 ppm, milk at 0.10 ppm, cattle kidney at 0.05 ppm; and by establishing a tolerance for residues of the insecticide DPXMP062, (R,S)
[[Page 58416]]
methyl 7chloro2,5dihydro2[[(methoxycarbonyl) [4
(trifluoromethoxy)phenyl] amino]carbonyl] indeno[1,2
e][1,3,4]oxadiazine4a(3H)carboxylate and its metabolite (INJT333), methyl 7chloro2,5dihydro2[[[4(trifluoromethoxy)phenyl]
amino]carbonyl]indeno[1,2e][1,3,4]oxadi azine 4a(3H)carboxylate, in/ on milk fat at 0.75 ppm and cattle fat at 0.75 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) (FRL57547).

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 the combined residues of indoxacarb and its Renantiomer in/on the following: apple at 1.0 ppm; apple, wet pomace at 3.0 ppm; Brassica, head and stem, subgroup at 5.0 ppm; cattle, goat, horse, sheep and hog fat at 0.75 ppm; cattle, goat, horse, sheep and hog meat at 0.03 ppm; cattle, goat, horse, sheep and hog meat byproducts at 0.02 ppm; corn, sweet, forage at 10 ppm; corn, sweet, kernel plus cob with husk removed at 0.02 ppm; corn, sweet, stover at 15 ppm; cotton gin byproducts at 15 ppm; cotton, undelinted seed at 2.0 ppm; lettuce, head at 4.0 ppm; lettuce, leaf at 10 ppm; milk at 0.10 ppm; milk fat at 3.0 ppm; pear at 0.20 ppm; vegetables, fruiting, group at 0.50 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 indoxacarb and its Renantiomer 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. DPXMP062 is a 75:25 mixture of the two enantiomers: indoxacarb which is
insecticidally active, and its Renantiomer, which is insecticidally inactive. DPXJW062 is a mixture of these same two enantiomers; however, they are in a 50:50 ratio. Toxicology data submitted on DPX JW062 were considered relevant and included in the evaluation.

The technical DPXMP062 (75:25) is toxicity category I for acute oral (rat); IV for acute dermal (rat), inhalation (rats) and primary dermal irritation (rabbit); and III for primary eye irritation (rabbit). The technical is considered a dermal sensitizer (guinea pig). Table 1. Subchronic, Chronic, and Other Toxicity Guideline No. Study Type Results 870.3100 90Day oral DPXMP062 (75% toxicity rodents indoxacarb / 25% rats enantiomer) NOAEL = Male (M) 3.1 mg/ kg/day, Female (F) 2.1 mg/kg/day LOAEL = M 6.0 mg/ kg/day, F 3.8 mg/ kg/day based on decreased body weight, body weight gain, food consumption and food efficiency. 870.3100 90Day oral DPXJW062 (50% toxicity rodents indoxacarb / 50% rats enantiomer) / NOAEL = M 8.0, F 4.6 mg/kg/day LOAEL = M 16, F 9.5 mg/kg/day based on mortality (F only), decreased. body weight, body weight gain, food consumption and food efficiency in rats. 870.3100 90Day oral DPXJW062 / NOAEL toxicity rodents = M 3.7, F 4.9 mg/ rats kg/day LOAEL = M 7.5, F 12 mg/kg/ day based on decreased in absolute body weight, body weight gain and food efficiency in rats. 870.3100 90Day oral DPXJW062 / NOAEL toxicity rodents = M23, F 16 mg/kg/ mice day LOAEL = M 44, F 30 mg/kg/day based on mortality (M only); increased reticulocytes and Heinz bodies and decreased body weight, weight gain, food consumption, food efficiency; and increased clinical signs (leaning to one side and/or with abnormal gait or mobility) (F only) in mice. 870.3150 90Day oral DPXJW062 / NOAEL toxicity in = 5.0 mg/kg/day nonrodentsdogs LOAEL = 19 mg/kg/ day based on hemolytic anemia, as indicated by decreased in HGB, RBCs; increases in platelets, increased reticulocytes; and secondary histopathologic findings indicative of blood breakdown (pigment in Kupffer cells, renal tubular epithelium, and spleen and bone marrow macrophages); increased in splenic EMH; and RBC hyperplasia in bone marrow in dogs. [[Page 58417]]
870.3200 28Day dermal DPXMP062 / NOAEL toxicity rats = 2,000 mg/kg/day LOAEL = >2,000 mg/ kg/day in rats. 870.3200 28Day dermal DPXMP062 / NOAEL toxicity rats = 50 mg/kg/day LOAEL = 500 mg/kg/ day based on decreased body weights, body weight gains, food consumption, and food efficiency in F, and changes in hematology parameters (increased reticulocytes), the spleen (increased absolute and relative weight M only, gross discoloration), clinical signs of toxicity in both sexes in rats. 870.3700a Prenatal DPXMP062 / developmental in Maternal NOAEL = rodentsrats 2.0 mg/kg/day, LOAEL = 4.0 mg/kg/ day based on decreased mean body weights, body weight gains, food consumption. Developmental NOAEL = 2.0 mg/kg/ day, LOAEL = 4.0 mg/kg/day based on decreased fetal weights. 870.3700a Prenatal DPXJW062 / developmental in Maternal NOAEL = rodentsrats 10 mg/kg/day, LOAEL = 100 mg/kg/ day based on mortality, clinical signs, and decreased mean body weights, body weight gains, and food consumption. Developmental NOAEL = 10 mg/kg/ day, LOAEL = 100 mg/kg/day based on decreased numbers of live fetuses/ litter. 870.3700a Prenatal DPXJW062 / developmental in Maternal NOAEL = rodentsrats 1.1 mg/kg/day LOAEL = 2.2 mg/kg/ day based on decreased mean body weights, body weight gains, food consumption, and food efficiency. Developmental NOAEL = 1.1 mg/kg/ day LOAEL = 2.2 mg/ kg/day based on decreased fetal body weights. 870.3700b Prenatal DPXJW062 / developmental in Maternal NOAEL = nonrodentsrabbi 500 mg/kg/day ts LOAEL = 1,000 mg/ kg/day based on slight decreases in maternal body weight gain and food consumption. Developmental NOAEL = 500 mg/kg/ day LOAEL = 1,000 mg/kg/day based on decr. fetal body weights and reduced ossification of the sternebrae. 870.3800 Reproduction and DPXJW062 / fertility Parental/Systemic effectsrats NOAEL = 1.5 mg/kg/ day LOAEL = 4.4 mg/ kg/ day based on decreased. body weights, body weight gains, and food consumption of F0 females, and increased spleen weights in the F0 and F1 females. Reproductive NOAEL = 6.4 mg/kg/day, LOAEL > 6.4 mg/kg/ day. Offspring NOAEL = 1.5 mg/kg/ day, LOAEL = 4.4 mg/kg/day based on decreased in the body weights of the F1 pups during lactation. 870.4100a Chronic toxicity DPXJW062 / NOAEL rodentsrats = M 5, F 2.1 mg/kg/ day, LOAEL = M 10, F 3.6 mg/kg/day based on decreased body weight, body weight gain, and food consumption and food efficiency; decreased HCT, HGB and RBC at 6 months in F only. no evidence of carcinogenic potential 870.4100b Chronic toxicity DPXJW062 / NOAEL dogs = M 2.3, F 2.4 mg/ kg/day LOAEL = M 18, F 19 mg/kg/day based on decreased. HCT, HGB and RBC; increased Heinz bodies and reticulocytes and associated secondary microscopic changes in the liver, kidneys, spleen, and bone marrow; increased absolute and relative liver weights. 870.4200 Carcinogenicityr DPXJW062 / see ats 870.4100a no evidence of carcinogenicity 870.4300 Carcinogenicitym DPXJW062 / NOAEL ice = M 2.6, F4.0 mg/ kg/day, LOAEL = M 14, F 20 mg/kg/day based on decreased body weight, body weight gain, and food efficiency and clinical signs indicative of neurotoxicity. no evidence of carcinogenicity 870.5100 Gene mutation DPXMP062 / strains TA97a, TA98, TA100 and TA1535 of S. typhimurium and strain WP2(uvrA) of E. coli were negative for mutagenic activity both with and without S9 activation for the concentration range 105000 g/plate 870.5100 Gene mutation DPXJW062 / strains TA97a, TA98, TA100 and TA1535 of S. typhimurium and strain WP2(uvrA) of E. coli were negative for mutagenic activity both with and without S9 activation for the concentration range 105000 g/plate. [[Page 58418]]
870.5300 Gene mutation DPXMP062 / negative for mutagenic activity for the following concentration ranges: 3.1250 g/mL ( S9); 3.1250 g/mL (+S9) 870.5300 Gene mutation DPXJW062 / negative for mutagenic activity for the following concentration ranges: Negative;1001,000 g/mL ( S9); 1001,000 g/mL (+S9), precipitate 1,000 g/mL 870.5375 Cytogenetics DPXMP062 / no evidence of chromosomal aberrations induced by the test article over background for the following concentration ranges: 15.71,000 g/mL (+S9) 870.5375 Cytogenetics DPXJW062 / no evidence of chromosomal aberrations induced by the test article over background for the following concentration ranges: 19300 g/mL ( S9), 19150 g/mL (+S9); partial insoluble and cytotoxicity 150 g/mL 870.5395 Cytogenetics DPXMP062 / no evidence of mutagenicity for the following dose ranges: 3,000 4,000 mg/kg males; 1,0002,000 mg/kgfemales 870.5395 Cytogenetics DPXJW062 / no evidence of mutagenicity at 2,500 or 5,000 mg/ kg
870.5550 Other effects DPXMP062/ no evidence of mutagenic activity at the following concentration range: 1.56200 g/mL; cytotoxicity was seen at concentrations of 100 g/mL 870.5550 Other effects DPXJW062 / No evidence of mutagenic activity at the following concentration range: 0.150 g/mL, cytotoxicity observed at 50 g/mL 870.6200a Acute DPXMP062 / NOAEL neurotoxicity = M 100, F 12.5 mg/ screening battery kg LOAEL = M 200 rat mg/kg based on decreased body weight gain, decreased food consumption, decreased forelimb grip strength, and decreased foot splay. F 50 mg/kg based on decreased body weight, body weight gain, and food consumption 870.6200a Acute DPXJW062 / NOAEL neurotoxicity >= M 2,000 mg/kg, screening battery F < 500 mg/kg rats LOAEL > M 2,000 mg/ kg, F < 500 mg/kg based on clinical signs, decreased body weight gains and food consumption, and FOB effects 870.6200b Subchronic DPXMP062 / NOAEL neurotoxicity = M 0.57, F 0.68 screening battery mg/kg/day LOAEL = rats M 5.6, F 3.3 mg/kg/ day based on decreased body weight and alopecia. 870.7485 Metabolism and Both DPXMP062 and pharmacokinetic DPXJW062 were rats extensively metabolized and the metabolites were eliminated in urine, feces, and bile. The metabolite profile for DPXJW062 was dose dependent and varied quantitatively between males and females. Differences in metabolite profiles were also observed for the different label positions (indanone and trifluoromethoxyph enyl rings). All biliary metabolites undergo further biotransformation in the gut. The proposed metabolic pathway for both DPXMP062 and DPXJW062 has multiple metabolites bearing one of the two ring structures. 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
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Population Adjusted Dose (aPAD or cPAD) is a modification of the RfD to accommodate this type of FQPA Safety Factor.

For nondietary 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 10⁶ or one in a million). Under certain specific circumstances, MOE calculations will be used for the carcinogenic risk assessment. In this nonlinear 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 (MOEcancer = point of departure/exposures) is calculated. A summary of the toxicological endpoints for indoxacarb and its Renantiomer used for human risk assessment is shown in the following Table 2:
Table 2. Summary of Toxicological Dose and Endpoints for Indoxacarb and its Renantiomer for Use in Human Risk Assessment Dose Used in Risk FQPA Safety Factor Exposure Scenario Assessment, Uncertainty (SF)<sup>*</sup> and Endpoint for Study and Toxicological Factor (UF) Risk Assessment Effects Acute dietary females 1350 years of NOAEL = 2.0 mg/kg/day FQPA SF = 1 aPAD = Developmental rat age UF = 100 Acute RfD = acute RfD toxicity study. 0.02 mg/kg FQPA SF = 0.02 mg/kg/ developmental LOAEL = day 4.0 mg/kg/day based on decreased fetal body weight. Acute dietary general population NOAEL= 12.5 mg/kg UF = FQPA SF = 1 aPAD = Acute oral rat including infants and children 100 Acute RfD = 0.12 acute RfD neurotoxicity study. mg/kg FQPA SF = 0.12 mg/kg/ LOAEL = 50 mg/kg based day on decreased body weight and body weight gain in females. Chronic dietary all populations NOAEL= 2.0 mg/kg/day UF FQPA SF = 1 cPAD = chr 90Day rat subchronic = 100 Chronic RfD = RfD FQPA SF = toxicity study, 90day 0.02 mg/kg/day 0.02 mg/kg/day rat neurotoxicity study, chronic/ carcinogenicity rat study. LOAEL = 3.3 mg/ kg/day based on decreased body weight, alopecia, body weight gain, food consumption and food efficiency; decreased hematocrit, hemoglobin and red blood cells only at 6 months. 3.3 mg/kg/day is the lowest NOAEL/ LOAEL of the 3 studies. Shortterm oral (17 days) Oral study NOAEL= 2.0 LOC for MOE = 100 Developmental rat (Residential) mg/kg/day (Residential, includes toxicity study. the FQPA SF) maternal LOAEL = 4.0 mg/kg/day based on decreased mean maternal body weights, body weight gains, and food consumption. Intermediate term oral (1 week Oral study NOAEL= 2.0 LOC for MOE = 100 90day rat subchronic several months) (Residential) mg/kg/day (Residential, includes toxicity study. LOAEL the FQPA SF) = 3.8 mg/kg/day based on decreased body weight, body weight gain, food consumption and food efficiency. Short (17 days), intermediate (1 Dermal study NOAEL= 50 LOC for MOE = 100 28day rat dermal weekseveral months), and long mg/kg/day (Occupational) LOC for toxicity study. LOAEL (several monthslifetime) term MOE = 100 = 500 mg/kg/day based dermal (Occupational/ Residential) (Residential, includes on decreased body the FQPA SF) weights, body weight gains, food consumption, and food efficiency in females, and changes in hematology parameters (increased reticulocytes), the spleen (increased absolute and relative weight males only, gross discoloration), and clinical signs of toxicity in both sexes. Shortterm inhalation (17 days) Oral study NOAEL= 2.0 LOC for MOE = 100 Rat developmental (Occupational/ Residential) mg/kg/day (inhalation (Occupational) LOC for toxicity study. absorption rate = MOE = 100 maternal LOAEL = 4.0 100%) (Residential, includes mg/kg/day based on the FQPA SF) decreased mean maternal body weights, body weight gains, and food consumption. Intermediate term inhalation (1 Oral study NOAEL= 2.0 LOC for MOE = 100 90day rat subchronic weekseveral months) (Occupational/ mg/kg/day (inhalation (Occupational) LOC for toxicity study. LOAEL Residential) absorption rate = MOE = 100 = 3.8 mg/kg/day based 100%) (Residential, includes on decreased body the FQPA SF) weight, body weight gain, food consumption and food efficiency. [[Page 58420]]
Longterm inhalation (several Oral study NOAEL= 2.0 LOC for MOE = 100 90day rat subchronic monthslifetime) (Occupational/ mg/kg/day (inhalation (Occupational) LOC for toxicity study, 90day Residential) absorption rate =100%) MOE = 100 rat neurotoxicity (Residential, includes study, chronic/ the FQPA SF) carcinogenicity rat study. LOAEL = 3.3 mg/ kg/day based on decreased body weight, body weight gain, food consumption and food efficiency; decreased hematocrit, hemoglobin and red blood cells only at 6 months. Cancer (oral, dermal, inhalation) ``not likely'' to be N/A No evidence of carcinogenic to humans carcinogenicity in either the rat or mouse in acceptable carcinogenicity studies and no evidence of mutagenicity. *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 180.564) for the combined residues or residues of indoxacarb and its Renantiomer, in or on a variety of raw agricultural commodities including apples, pears, Brassica (head and stem subgroup), cotton, leaf lettuce, head lettuce, fruiting vegetable group, sweet corn, milk, and the meat, meat byproducts and fat of cattle, goats, horses, hogs and sheep. Risk assessments were conducted by EPA to assess dietary exposures from indoxacarb and its Renantiomer in food as follows:
i. Acute exposure. Acute dietary risk assessments are performed for a fooduse pesticide if a toxicological study has indicated the possibility of an effect of concern occurring as a result of a one day or single exposure. The Dietary Exposure Evaluation Model (DEEM) analysis evaluated the individual food consumption as reported by respondents in the USDA 19891992 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 acute exposure assessments: acute Tier 1 analysis assuming tolerance level residues and 100% crop treated (CT) information was performed; however, dietary risk estimates from residues in food exceeded Agency's level of concern (> 100% aPAD). An acute Tier 2 (partially refined analysis) dietary assessment was performed with use of anticipated residues (ARs) from field trial data, processing factors (where applicable), and 100% CT. Note that the Tier 2 assessment is deterministic in that point estimates were used for all residues and the conservative assumption of 100% CT was made. Additional refinement using % CT data would result in even lower exposure estimates from residues in food.
ii. Chronic exposure. In conducting this chronic dietary risk assessment, the DEEM analysis evaluated the individual food consumption as reported by respondents in the USDA 19891992 nationwide CSFII and accumulated exposure to the chemical for each commodity. The following assumptions were made for the chronic exposure assessments: tolerance level residues and 100% CT (Tier 1). Additional refinement using less than 100% CT data would result in even lower exposure estimates from residues in food.
iii. Anticipated residue and percent crop treated Information. Section 408(b)(2)(E) authorizes EPA to use available data and information on the anticipated residue levels of pesticide residues in food and the actual levels of pesticide chemicals that have been measured in food. If EPA relies on such information, EPA must require that data be provided 5 years after the tolerance is established, modified, or left in effect, demonstrating that the levels in food are not above the levels anticipated. Following the initial data submission, EPA is authorized to require similar data on a time frame it deems appropriate. As required by section 408(b)(2)(E), EPA will issue a data callin for information relating to anticipated residues to be submitted no later than 5 years from the date of issuance of this tolerance.

2. Dietary exposure from drinking water. The Agency lacks sufficient monitoring exposure data to complete a comprehensive dietary exposure analysis and risk assessment for indoxacarb and its R enantiomer 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 indoxacarb and its Renantiomer.

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 the Screening Concentration in Ground Water Model (SCIGROW), 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 screeninglevel assessment for surface water. The GENEEC model is a subset of the PRZM/EXAMS model that uses a specific highend 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
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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 indoxacarb and its R enantiomer they are further discussed in the aggregate risk sections below.

Based on the PRZM/EXAMS and SCIGROW models the estimated environmental concentrations (EECs) of indoxacarb and its Renantiomer for acute exposures are estimated to be 3.81 parts per billion (ppb) for surface water and 0.02 ppb for ground water. The EECs for chronic exposures are estimated to be 0.56 ppb for surface water and 0.02 ppb for ground water.

3. From nondietary exposure. The term ``residential exposure'' is used in this document to refer to nonoccupational, nondietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets). Indoxacarb and its R enantiomer is not registered for use on any sites that would result in residential exposure.

4. Cumulative exposure to substances with a common mechanism of toxicity. Section 408(b)(2)(D)(v) requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider ``available information'' concerning the cumulative effects of a particular pesticide's residues and ``other substances that have a common mechanism of toxicity.''

EPA does not have, at this time, available data to determine whether indoxacarb and its Renantiomer 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, indoxacarb and its Renantiomer 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 indoxacarb and its Renantiomer 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 childreni. 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 evidence of susceptibility from either in utero or neonatal exposure to both rat and rabbit young with either DPXMP062 or DPXJW062.

iii. Conclusion. There is a complete toxicity data base for indoxacarb and its Renantiomer and exposure data are complete or are estimated based on data that reasonably accounts for potential exposures. The FQPA safety factor is 1X. EPA determined that the 10X safety factor to protect infants and children should be removed because, there is no indication of quantitative or qualitative increased susceptibility of rats or rabbits to in utero and/or postnatal exposure; the requirement of a developmental neurotoxicity study is not based on the criteria reflecting special concern for the developing fetuses or young which are generally used for requiring a DNT studyand a safety factor (e.g.: neuropathy in adult animals; CNS malformations following prenatal exposure; brain weight or sexual maturation changes in offspring; and/or functional changes in offspring)and therefore does not warrant an FQPA SF; the dietary (food and drinking water) exposure assessments will not under estimate the potential exposures for infants and children; and there are no registered residential uses at the current time.

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 fo