Pesticides; tolerances in food, animal feeds, and raw agricultural commodities: methyl,
[Federal Register: June 10, 1999 (Volume 64, Number 111)]
[Rules and Regulations]
[Page 31129-31136]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr10jn99-13]
ENVIRONMENTAL PROTECTION AGENCY
[OPP-300873; FRL-6085-4]
RIN 2070-AB78
Kresoxim-methyl; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule.
SUMMARY: This regulation establishes tolerances for combined residues of kresoxim-methyl and its metabolites in or on pome fruit, grapes, pecans, apple pomace, raisins, and meat byproducts of cattle, sheep and goats. BASF Corporation requested these tolerances under the Federal Food, Drug, and Cosmetic Act, as amended by the Food Quality Protection Act of 1996. DATES: This regulation is effective June 10, 1999. Objections and requests for hearings must be received by EPA on or before August 9, 1999. ADDRESSES: Written objections and hearing requests, identified by the docket control number, [OPP-300873], must be submitted to: Hearing Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M St., SW., Washington, DC 20460. Fees accompanying objections and hearing requests shall be labeled ``Tolerance Petition Fees'' and forwarded to: EPA Headquarters Accounting Operations Branch, OPP (Tolerance Fees), P.O. Box 360277M, Pittsburgh, PA 15251. A copy of any objections and hearing requests filedwith the Hearing Clerk identified by the docket control number, [OPP-300873], must also be submitted to: Public Information and Records Integrity Branch, Information Resources and Services Division (7502C), Office of Pesticide Programs, Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. In person, bring a copy of objections and hearing requests to Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
A copy of objections and hearing requests filedwith the Hearing Clerk may be submitted electronically by sending electronic mail (e- mail) to: opp-docket@epa.gov. Copies of objections and hearing requests must be submitted as an ASCII file avoiding the use of special characters and any form of encryption. Copies of objections and hearing requests will also be accepted on disks in WordPerfect 5.1/6.1 file format or ASCII file format. All copies of objections and hearing requests in electronic form must be identified by the docket control number [OPP-300873]. No Confidential Business Information (CBI) should be submitted through e-mail. Electronic copies of objections and hearing requests on this rule may be filedonline at many Federal Depository Libraries. FOR FURTHER INFORMATION CONTACT: By mail: Mary L. Waller, Product Manager 21, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. Office location, telephone number, and e-mail address: Rm. 249, Crystal Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA, (703) 308-9354, waller.mary@epa.gov. SUPPLEMENTARY INFORMATION: In the Federal Register of March 10, 1999 (64 FR 11874) (FRL-6063-3), EPA issued a notice pursuant to section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a as amended by the Food Quality Protection Act of 1996 (FQPA) (Public Law 104-170) announcing the filing of a pesticide petition (PP) 7F4880 for tolerances by BASF Corporation, 26 Davis Drive, P.O. Box 13528, Research Triangle Park, NC 27709-3528. This notice included a summary of the petition prepared by BASF Corporation, the registrant. There were no comments received in response to the notice of filing.
The petition requested that 40 CFR part 180 be amended by establishing tolerances for the combined residues of the fungicide kresoxim-methyl, (BAS 490F) or (methyl (E)-2-[2-(2-methylphenoxy)- methyl]phenyl-2-(methoxyimido)acetate) and its metabolites as follows: (BF 490-1) or (E)-2-[2-(2-methylphenoxy)methyl]-phenyl-2- (methoxyimido)acetic acid; (BF 490-2) or (E)-2-[2-(2- hydroxymethylphenoxy)methyl]-phenyl-2-(methoxyimido)acetic acid (free and glucose conjugated); and (BF 490-9) or (E)-2-[2-(4-hydroxy-2- methylphenoxy)-methyl]phenyl-2-(methoxyimido)acetic acid (free and glucose conjugated) in or on pome fruit at 0.5 parts per million (ppm), grapes at 1.0 ppm, pecans, at 0.15 ppm, apple pomace at 1.0 ppm, and raisins at 1.5
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ppm. The petition also requested that 40 CFR part 180 be amended by establishing tolerances in or on meat byproducts of cattle, sheep and goats at 0.01 ppm for the residues of the metabolite (BF 490-1) or ((E)-2-[2-(2-methylphenoxy)methyl]-phenyl-2-(methoxyimido)acetic acid) resulting from the use of the fungicide kresoxim-methyl.
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Background and Statutory Findings
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).
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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 kresoxim- methyl and to make a determination on aggregate exposure, consistent with section 408(b)(2), for tolerances for combined residues of kresoxim-methyl and its metabolites in or on pome fruit, grapes, pecans, apple pomace, raisins, and meat byproducts of cattle, sheep and goats. EPA's assessment of the dietary exposures and risks associated with establishing the tolerances follows.
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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 kresoxim-methyl are discussed in this unit.
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Acute toxicity. A battery of acute toxicity studies using technical kresoxim-methyl resulted in the following: an acute rat oral LD‹INF›50‹/INF› › 5,000 milligrams/kilogram(mg/kg) (toxicity category IV); an acute rat dermal LD‹INF›50‹/INF› › 2,000 mg/kg (toxicity category III); an acute rat inhalation LC‹INF›50‹/INF› › 5.6 milligrams/liter(mg/L) (toxicity category IV); mild eye irritation in a primary eye irritation study using rabbits (toxicity category III); no irritation in a primary skin irritation study using rabbits (category IV); and no sensitization demonstrated in a dermal sensitization study using guinea pigs.
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Subchronic toxicity. i. In a 90-day oral toxicity study, rats were fed kresoxim-methyl at dose levels of 0, 500, 2,000, 8,000, and 16,000 parts per million (ppm) (0, 36, 146, 577, and 1,170 mg/kg/day for males and 0, 43, 172, 672, and 1,374 mg/kg/day for females). The Lowest Observed Adverse Effect Level (LOAEL) for male rats was 8,000 ppm based on elevated serum GGT. A LOAEL was not established for females. The No Observed Adverse Effect Level (NOAEL) for males was 2,000 ppm and for females was 16,000 ppm.
ii. In a 90-day oral toxicity study, mice were fed kresoxim-methyl at levels of 0, 250, 1,000, 4,000, and 8,000 ppm (0, 57, 230, 909, and 1,937 mg/kg/day for males and 0, 80, 326, 1,326 and 2,583 mg/kg/day for females). A LOAEL was not determined for either sex. The NOAEL for males and females was 8,000 ppm.
iii. In a 21-day dermal toxicity study, 5 male and 5 female rats were treated with kresoxim-methyl by dermal occlusion at doses of 0 and 1,000 mg/kg/day, 6 hours/day for 21 days. The NOAEL for males and females was 1,000 mg/kg/day. A LOAEL was not determined.
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Developmental toxicity. i. In a developmental toxicity study, rats were gavaged with kresoxim-methyl at dose levels of 0, 100, 400, or 1,000 mg/kg/day on gestation days 6-15. No clinical signs of toxicity were observed in any treated animals during the study and no treatment-related gross abnormalities were observed at maternal necropsy. The maternal NOAEL was ‹gr-thn-eq› 1,000 mg/kg/day and the maternal LOAEL was not determined. There were no treatment-related external, visceral, or skeletal malformations/variations observed in any of the fetuses. The developmental NOAEL was ‹gr-thn-eq› 1,000 mg/ kg/day and the developmental LOAEL was not determined.
ii. In a developmental toxicity study, rabbits were gavaged with kresoxim-methyl at dose levels of 0, 100, 400 or 1,000 mg/kg/day on gestation days 7-19. No clinical signs of toxicity were observed in any treated animals during the study and no treatment-related gross abnormalities were observed at maternal necropsy. The maternal NOAEL was ‹gr-thn-eq› 1,000 mg/kg/day and the maternal LOAEL was not determined. There were no differences between treated and control groups for number of corpora lutea/doe, implantation sites/doe, pre- and post-implantation loss, resorptions/doe, fetuses/litter, fetal sex ratios, gravid uterine or fetal body weights, or number of dead fetuses. The overall incidence rates for litters containing fetuses with major malformations in the 0, 100, 400, and 1,000 mg/kg/day groups were 7/13, 7/14, 11/15, and 10/14, respectively. There was no statistically significant difference between control and treated groups of fetuses regarding the number of external, soft-tissue, or skeletal malformations/variations with the exception of fetal incidence of fused sternebrae in the low dose group compared to the controls (p ‹ 0.05). Since a dose-response relationship was not apparent, toxicological significance could not be established. The developmental NOAEL was ‹gr-thn-eq› 1,000 mg/kg/day and the developmental toxicity LOAEL was not identified.
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Reproductive Toxicity. In a 2-generation reproduction study, 25 rats/sex/dose were fed kresoxim-methyl at dose levels of 0, 50, 1,000, 4,000, or 16,000 ppm for two generations. Two litters were produced in the first generation (F‹INF›1a‹/INF› and F‹INF›1b‹/INF›) and one litter in the second generation (F‹INF›2‹/INF›). Premating doses for the F‹INF›0‹/INF› males were 5.1, 102.6, 411.0, and 1,623.1 mg/kg, respectively and for F‹INF›0‹/INF› females were 5.6, 108.7, 437.2 and 1,741.1 mg/kg, respectively. Premating doses for the F‹INF›1‹/INF› males were 4.4, 88.3, 362.7, and 1,481.6 mg/kg and for the F‹INF›1‹/INF› females were 5.0, 100.8, 416.6, and 1,652.6 mg/kg, respectively. Animals were given test or control diet for at least 10 weeks then mated within the same dose group. F‹INF›1‹/INF› animals were chosen from the F‹INF›1a‹/INF› litters and weaned on the same diet as their parents. At least 22 litters/group were produced in
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each generation. All animals were exposed to test material either in the diet or during lactation until sacrifice.
There were no dose- or treatment-related clinical signs of toxicity in the parental animals of either sex or generation. No dose- or treatment-related gross or histological abnormalities were observed at necropsy in either parent or first generation animals of either sex. The LOAEL for systemic/postnatal developmental toxicity was 4,000 ppm based on reduced body weights and body weight gains of the parent and first generation parental animals and delayed growth and maturation of the first and second generation pups. The NOAEL for systemic toxicity was 1,000 ppm. No treatment-related effects were observed in the reproductive performances of either generation. There were no dose- or treatment-related clinical signs of toxicity in the offspring of either generation. The NOAEL for reproductive toxicity was ‹gr-thn-eq› 16,000 ppm and the LOAEL for reproductive toxicity was not identified.
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Mutagenicity. No mutagenicity was noted in the following assays: reverse gene mutation, S. typhimurium, E. coli; forward gene mutation - HGPRT locus; chromosome aberrations, human lymphocyte cultures; mouse bone marrow micronucleus; unscheduled DNA synthesis, rat hepatocyte cultures; and unscheduled DNA synthesis, rat hepatocytes (in vivo/in vitro procedure).
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Chronic Toxicity. i. In a 2-year chronic feeding study, 20 rats/ sex/dose were fed kresoxim-methyl at dose levels of 0, 200, 800, 8,000, or 16,000 ppm (0, 9, 36, 370 or 746 mg/kg/day for males and 0, 12, 48, 503, or 985 mg/kg/day for females). The LOAEL for male and female rats was 8,000 ppm based in males on the increase in SGGT levels, liver weight and histopathological changes, and in females on roughly 10% lowered body weights and weight gains throughout most of the study. The NOAEL for both sexes was 800 ppm.
ii. In a 1-year chronic feeding study, 5 dogs/sex/dose were fed kresoxim-methyl at levels of 0, 1,000, 5,000 or 25,000 ppm (0, 27, 138, or 714 mg/kg/day for males and 0, 30, 146, or 761 mg/kg/day for females). The LOAEL for males was 25,000 ppm based on decreased mean body weight and body weight gain and decreased food efficiency. A LOAEL was not identified for females. The NOAEL for males was 5,000 ppm, and for females was 25,000 ppm.
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Carcinogenicity. i. In a 2-year oncogenicity feeding study, 50 rats/sex/dose were fed kresoxim-methyl at dose levels of 0, 200, 800, 8,000, or 16,000 ppm (0, 9, 36, 375, and 770 mg/kg/day for males and 0, 12, 47, 497, and 1,046 mg/kg/day for females). Clinical observations and mortality were not affected by treatment in either sex of rats. Body weights and body weight gains of males and females were decreased relative to controls in the respective 8,000 and 16,000 ppm groups throughout most or all of the study. The incidence of gross liver masses increased in both sexes (p ‹ls-thn-eq› 0.05 in 8,000 ppm males; p ‹ls-thn-eq› 0.01 in 8,000 and 16,000 ppm females). This was correlated in males with dose-related increases in the incidence of microscopic lesions including eosinophilic cell foci, mixed cell foci, cellular hypertrophy (dose related; p ‹ls-thn-eq› 0.05 or 0.01 at 16,000 ppm), and biliary cysts (p ‹ls-thn-eq› 0.05 at 8,000 ppm) and in females with altered cell foci, mixed cell foci, bile duct proliferation, and cholangiofibrosis (p ‹ls-thn-eq› 0.05, 0.01, or 0.001 at 16,000 ppm). The liver (with bile ducts) is therefore implicated as a target organ in both sexes of rats. The increased incidence in females of gross ovarian masses (p ‹ls-thn-eq› 0.05 at 16,000 ppm), microscopic ovarian cysts (p ‹ls-thn-eq› 0.001 at 800 and 16,000 ppm), uterine/cervical dilation (p ‹ls-thn-eq› 0.01 at 800 and 16,000 ppm) and brain hemorrhage (p ‹ls-thn-eq› 0.05 at 16,000 ppm) and in males of enlarged testes (p ‹ls-thn-eq› 0.05 at 800 and 8,000 ppm) did not appear to be treatment-related. The LOAEL for both male and female rats was 8,000 ppm. The LOAEL for males was based on the minor decrease in body weight and body weight gain and the increase in gross and microscopic liver (and biliary) lesions. The LOAEL in females was based on the lowered body weights and weight gains and on the increased incidence of liver masses. The NOAEL for both sexes was 800 ppm. Liver carcinoma was the primary neoplastic finding in both sexes of rats, consistent with the histopathological findings.
ii. In an 18-month feeding study, mice were fed kresoxim-methyl at dose levels of 0, 400, 2,000, and 8,000 ppm (0, 60, 304, and 1,305 mg/ kg/day for males and 0, 81, 400, and 1,662 mg/kg/day) for 18 months. An additional 10 animals were treated for 12 months in a satellite study. The LOAEL was 2,000 ppm (400 mg/kg/day) for females, based on decreased weight gain and 8,000 ppm (1,350 mg/kg/day for males, based on decreased weight gain and liver amyloidosis. The NOAEL was 400 ppm (81 mg/kg/day) for females and 2,000 ppm (304 mg/kg/day) for males. At the doses tested, there was not a treatment related increase in tumor incidence when compared to controls. Dosing was considered adequate and the high dose rate was above the limit dose of 1,000 mg/kg/day for both sexes.
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Metabolism. In a metabolism study, rats were gavaged with kresoxim-methyl at dose levels of 50 or 500 mg/kg or 15-day repeated doses of 50 mg/kg, or as a single intravenous dose of 5 mg/kg/day. Radiolabeled test compound was included in one 500 mg/kg dose group to facilitate metabolite identification. Biliary metabolites were assessed in rats with cannulated bile ducts given an oral dose of 50 or 500 mg/ kg/day.
Orally administered test compound was widely distributed and quickly eliminated. Results indicated there was no bioaccumulation. In both sexes, the major routes of excretion were feces and the urine. No radioactivity was detected in exhaled air. A total of 32 different metabolites were identified in the urine, feces, bile, plasma, liver, and kidneys of rats. There were some sex, dose, route, and label- dependent differences in the metabolite profiles.
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Neurotoxicity. i. In an acute oral neurotoxicity, 10 rats/sex/ dose were gavaged with kresoxim-methyl at dose levels of 0, 500, 1,00, or 2,000 mg/kg. No signs of neurotoxicity were observed at any dose level and no systemic toxicity was observed at any dose level. A LOAEL was not established. The NOAEL for acute neurotoxicity is 2,000 mg/kg.
ii. In a subchronic oral neurotoxicity study, 10 rats/sex/dose were fed kresoxim-methyl at dose levels of 0, 1,000, 4,000 or 16,000 ppm (0, 78, 317, 1,267 mg/kg/day) for 3 months. All animals survived to scheduled termination. There were statistically significant decreases in body weight, body weight gain, and food consumption on some days only at the high-dose level for males and females. No effects were observed at the other dose levels. There were no observable signs of a neurotoxic effect at any dose level. Functional observation battery and motor activity remained comparable to controls throughout the study an no neuropathological endpoints were observed during the histological examinations. The LOAEL for systemic toxicity is 16,000 ppm for males and females based on decreases in body weight, body weight gain, and food consumption. The NOAEL for systemic toxicity is 4,000 ppm for male and female rats, and is ‹gr-thn-eq› 16,000 ppm for neurotoxicity.
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Toxicological Endpoints
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Acute toxicity. An acute endpoint was not selected because no adverse effects resulting from a single exposure were identified in an acute
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neurotoxicity study in rats, and developmental toxicity studies in the rat and rabbit.
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Short- and intermediate-term toxicity. A short- and intermediate -term endpoint was not selected because no dermal or systemic toxicity was seen in a 21-day dermal toxicity study in rats.
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Chronic toxicity. EPA has established the Reference Dose (RfD) for kresoxim-methyl at 0.36 mg/kg/day. This RfD is based on a 2-year oncogenicity feeding study in rats. The FQPA safety factor was reduced to 1X for chronic dietary exposure because there was no increase in susceptibility identified in developmental or reproductive toxicity studies. Therefore, the chronic PAD (chronic population adjusted dose or cPAD) and the chronic RfD are identical.
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Chronic dermal toxicity. EPA selected the RfD of 0.36 mg/kg/day to assess long-term dermal exposure. This RfD (identified above) is from an oral study and, based on available data, dermal absorption is expected to be equivalent to oral absorption (approximately 63-70%). Therefore a dermal absorption factor was not required for risk calculations. This endpoint was selected for occupational exposure only as there are no residential uses of kresoxim-methyl.
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Carcinogenicity. Kresoxim-methyl has been classified as a ``likely human carcinogen''. The Q‹INF›1‹/INF›* for kresoxim-methyl is 2.90 x 10‹SUP›-3‹/SUP›. The Q‹INF›1‹/INF›* is based on the female rat combined (adenomas and/or carcinomas) liver tumor rates from a 2-year oncogenicity feeding study.
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Exposures and Risks
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From food and feed uses. There are no food or feed uses currently registered for kresoxim-methyl. In today's action, tolerances are being established at 40 CFR 180.554 for combined residues of the fungicide kresoxim and its metabolites in or on pome fruit at 0.5 ppm, grapes at 1.0 ppm, pecans at 0.15 ppm, apple pomace at 1.0 ppm, raisins at 1.5 ppm, and meat byproducts of cattle, sheep and goats at 0.01 ppm. Risk assessments were conducted by EPA to assess dietary exposures from kresoxim methyl as follows:
Section 408(b)(2)(E) authorizes EPA to use available data and information on the anticipated residue levels of pesticide residues in food and the actual levels of pesticide chemicals that have been measured in food. If EPA relies on such information, EPA must require that data be provided 5 years after the tolerance is established, modified, or left in effect, demonstrating that the levels in food are not above the levels anticipated. Following the initial data submission, EPA is authorized to require similar data on a time frame it deems appropriate. As required by section 408(b)(2)(E), EPA will issue a data call-in for information relating to anticipated residues to be submitted no later than 5 years from the date of issuance of this tolerance.
i. Acute exposure and risk. 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. No toxicological endpoint attributable to a single (acute) dietary exposure was identified.
ii. Chronic exposure and risk. The chronic dietary exposure analysis used the cPAD of 0.36 mg/kg/day which applies to all population subgroups. Anticipated residue values were used and EPA assumed that 100% of all crops having kresoxim-methyl tolerances were treated. EPA generally has no concern for exposures below 100% of the cPAD because the cPAD represents the level at or below which daily aggregate dietary exposure over a lifetime will not pose appreciable risks to human health. The Agency estimated that chronic dietary exposure to kresoxim-methyl will utilize 0.1% of the cPAD for the U.S. population and 0.2% of the cPAD for the most highly exposed population subgroup, non-nursing infants. The chronic dietary risk does not exceed the Agency's level of concern.
iii. Dietary cancer risk. Kresoxim-methyl is classified as a ``likely human carcinogen'' with a Q‹SUP›*‹/SUP› of 2.90 x 10‹SUP›-3‹/SUP›. The upper bound lifetime cancer risk estimated for U.S. population is 5.7 x 10‹SUP›-7‹/SUP› and is below the Agency's level of concern (cancer risks greater than 1 x 10‹SUP›-6‹/SUP›). Therefore, the dietary food cancer risk to kresoxim-methyl is below the Agency's level of concern.
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From drinking water. Kresoxim-methyl is relatively short lived and therefore, unlikely to leach to ground water or move offsite to surface water in significant concentrations. However, the major acid degradate/metabolite (BF 490-1) has physical/chemical characteristics in common with pesticides that are known to leach to groundwater or to move offsite to surface water. Possible contamination of groundwater and surface water by BF 490-1 may occur when applied to fields with one or more of the following characteristics: alkaline soils, low organic matter, high sand, shallow groundwater table, and nearby bodies of water.
i. Acute exposure and risk. No acute risk is expected from exposure to kresoxim-methyl.
ii. Chronic exposure and risk. The Agency used the Screening Concentration in Ground Water (SCI-GROW) screening model to determine the estimated environmental concentration (EEC) in ground water and the Pesticide Root Zone model-Exposure Analysis Modeling (PRZM-EXAMS) to determine the EEC in surface water. Drinking water levels of comparison (DWLOC) which represent the upper limit of a chemical's concentration in drinking water that will result in an acceptable aggregate exposure were calculated for comparison to the EEC's from the SCI-GROW and PRZM- EXAMS model values. The combined ground water EEC for kresoxim-methyl and BF 490-1 is 4.1 parts per billion (ppb) (groundwater screening for kresoxim-methyl is negligible and groundwater screening concentration for BF 490-1 is 4.1 ppb). The combined surface water EEC for kresoxim- methyl and BF 490-1 is 5.0 ppb. The combined groundwater EEC of 4.1 ppb and the combined surface water EEC of 5.0 ppb are substantially lower than the Agency's chronic (non-cancer) DWLOC of 12,593 ppb for the U.S. population and the chronic (non-cancer) DWLOC of 3,591 ppb for the most highly exposed population subgroup, non-nursing infants. Therefore, the Agency concludes with reasonable certainty that residues of kresoxim- methyl and BF 490-1 do not contribute significantly to the aggregate chronic (non-cancer) human health risk.
The Agency calculated a chronic (cancer) DWLOC of 4.9 ppb for the U.S. population. The combined groundwater EEC of 4.1 ppb is lower than the chronic (cancer) DWLOC of 4.9 ppb. The PRZM-EXAMS surface water EEC of 5.0 ppb produces a cancer risk estimate in the range of 10E6. However, EPA believes this overstates the cancer risk because the chronic dietary exposure estimates for kresoxim-methyl assumed 100% crop treated. The Agency calculated the expected market share for kresoxim-methyl and assumed that kresoxim-methyl would capture 100% of the market share from the alternative product with the highest use. The maximum kresoxim-methyl percent crop treatment estimates for apples, pears, pecans, and grapes are 70%, 55%, 55%, and 30%, respectively. The Agency considers these estimates to be conservative with actual use rates of kresoxim-methyl likely to be considerably lower. The Agency believes that actual dietary exposure to kresoxim-methyl and BF 490-1 will
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decrease at least by a factor of › 2% resulting in a combined surface water DWLOC for kresoxim-methyl and BF 490-1 of ‹gr-thn-eq› 5.0 ppb.
Section 408(b)(2)(F) states that the Agency may use data on the actual percent of food treated (PCT) for assessing chronic dietary risk only if the Agency can make the following findings: That the data used are reliable and provide a valid basis to show what percentage of the food derived from such crop is likely to contain such pesticide residue; that the exposure estimate does not underestimate exposure for any significant subpopulation group; and if data are available on pesticide use and food consumption in a particular area, the exposure estimate does not understate exposure for the population in such area. In addition, the Agency must provide for periodic evaluation of any estimates used. To provide for the periodic evaluation of the estimate of percent of crop treated as required by the section 408(b)(2)(F), EPA may require registrants to submit data on PCT. The Agency believes that the three conditions, discussed in section 408(b)(2)(F) in this unit concerning the Agency's responsibilities in assessing chronic dietary risk findings, have been met. The PCT estimates are derived from Federal and private market survey data, which are reliable and have a valid basis. Typically, a range of estimates are supplied and the upper end of this range is assumed for the exposure assessment. By using this upper end estimate of the PCT, the Agency is reasonably certain that the percentage of the food treated is not likely to be underestimated. The regional consumption information and consumption information for significant subpopulations is taken into account through EPA's computer-based model for evaluating the exposure of significant subpopulations including several regional groups. Use of this consumption information in EPA's risk assessment process ensures that EPA's exposure estimate does not understate exposure for any significant subpopulation group and allows the Agency to be reasonably certain that no regional population is exposed to residue levels higher than those estimated by the Agency.
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From non-dietary exposure. Kresoxim-methyl has no proposed or registered residential uses. Therefore, no non-occupational, non- dietary exposure and risk are expected.
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Cumulative exposure to substances with 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 kresoxim-methyl 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, kresoxim-methyl 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 kresoxim-methy 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)(FRL-5754-7).
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Aggregate Risks and Determination of Safety for U.S. Population
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Acute risk. No acute risk are expected because no acute dietary endpoint was determined.
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Chronic risk. Using the exposure assumptions described in this unit, EPA has concluded that aggregate exposure to kresoxim-methyl from food will utilize 0.1% of the cPAD for the U.S. population. The major identifiable subgroup with the highest aggregate exposure is discussed below. EPA generally has no concern for exposures below 100% of the cPAD because the cPAD represents the level at or below which daily aggregate dietary exposure over a lifetime will not pose appreciable risks to human health. Despite the potential for exposure to kresoxim- methyl in drinking water, EPA does not expect the aggregate exposure to exceed 100% of the cPAD.
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Aggregate cancer risk for U.S. population. The upper bound lifetime cancer risk estimated for U.S. population is in the range of 10E6. The Agency's general level of concern for cancer risks is for risks greater than risks in the range of 1 x 10‹SUP›-6‹/SUP›. Use of percent crop treated estimates will significantly lower the combined surface water estimates and thus significantly lower the risk estimate. Therefore, the Agency concludes with reasonable certainty that no harm will result from aggregate exposure to kresoxim-methyl and its metabolites.
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Determination of safety. Based on these risk assessments, EPA concludes that there is a reasonable certainty that no harm will result from aggregate exposure to residues of kresoxim-methyl and its metabolites.
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Aggregate Risks and Determination of Safety for Infants and Children
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Safety factor for infants and children--i. In general. In assessing the potential for additional sensitivity of infants and children to residues of kresoxim-methyl and its metabolites, EPA considered data from developmental toxicity studies in the rat and rabbit and a 2-generation reproduction study in the rat. The developmental toxicity studies are designed to evaluate adverse effects on the developing organism resulting from maternal pesticide exposure gestation. Reproduction studies provide information relating to effects from exposure to the pesticide on the reproductive capability of mating animals and data on systemic toxicity.
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 pre- and post-natal toxicity and the completeness of the database 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. EPA believes that reliable data support using the standard uncertainty factor (usually 100 for combined inter- and intra-species variability) and not the additional tenfold MOE/ uncertainty factor when EPA has a complete data base under existing guidelines and when the severity of the effect in infants or children or the potency or unusual toxic properties of a compound do not raise concerns regarding the adequacy of the standard MOE/safety factor.
ii. Pre- and post-natal sensitivity. In the prenatal developmental toxicity studies in rat and rabbit fetuses, no evidence of developmental toxicity in fetuses was seen at the limit dose. In the 2- generation reproduction study in rats, offspring effects occurred only at parentally toxic dose levels.
iii. Conclusion. There is a complete toxicity database for kresoxim-methyl and exposure data is complete or is estimated based on data that reasonably accounts for potential exposures. Taking
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into account the lack of any special pre- or post-natal susceptibility and the completeness of the toxicity and exposure data base, EPA concluded that an additional tenfold safety factor was not needed to protect the safety of infants and children.
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Acute risk. No acute risk is expected because no acute dietary endpoint was identified.
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Chronic risk. Using the exposure assumptions described in this unit, EPA has concluded that aggregate exposure to kresoxim-methyl from food will utilize 0.2% of the cPAD for the most highly exposed population subgroup, non-nursing infants. EPA generally has no concern for exposures below 100% of the cPAD because the cPAD represents the level at or below which daily aggregate dietary exposure over a lifetime will not pose appreciable risks to human health. Despite the potential for dietary exposure to kresoxim-methyl in drinking water and from non-dietary, non-occupational exposure, EPA does not expect the aggregate exposure to exceed 100% of the cPAD.
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Determination of safety. Based on these risk assessments, EPA concludes that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to kresoxim-methyl residues.
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Other Considerations
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Metabolism In Plants and Animals
The nature of the residues in plants and animals is adequately understood. The residues of concern in plants are kresoxim-methyl, (BAS 490F or methyl (E)-2-[2-(2-methylphenoxy)-methyl]phenyl-2- (methoxyimido)acetate) and its metabolites as follows: BF 490-1 or (E)- 2-[2-(2-methylphenoxy)methyl]-phenyl-2-(methoxyimido)acetic acid; BF 490-2 or (E)-2-[2-(2-hydroxymethylphenoxy)methyl]-phenyl-2- (methoxyimido)acetic acid (free and glucose conjugated); and BF 490-9 or (E)-2-[2-(4-hydroxy-2-methylphenoxy)-methyl]phenyl-2- (methoxyimido)acetic acid (free and glucose conjugated). The residue of concern in animals is the metabolite BF 490-1 or (E)-2-[2-(2- methylphenoxy)methyl]-phenyl-2-(methoxyimido)acetic acid.
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Analytical Enforcement Methodology
Adequate enforcement methodology high performance liquid chromatography/using ultra violet detection (HPLC/ULV) is available to enforce the tolerance expression. The method may be requested from: Calvin Furlow, PRRIB, IRSD (7502C), Office of Pesticide Programs, Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. Office location and telephone number: Rm 101FF, Crystal Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA, (703) 305-5229.
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Magnitude of Residues
The Agency has concluded that residue data submitted in support of the tolerances for kresoxim-methyl as follows: 0.5 ppm for pome fruit, 1.0 ppm for grapes, 0.15 ppm for pecans, 1.0 for apple pomace, 1.5 ppm for raisins, and 0.01 ppm for meat byproducts of cattle, sheep and goats are adequate.
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International Residue Limits
There are no CODEX, Canadian, or Mexican maximum residue limits for kresoxim-methyl.
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Rotational Crop Restrictions
Rotational crop restrictions are not required as rotation to other crops is not anticipated.
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Conclusion
Therefore, tolerances are established for combined residues of kresoxim-methyl (methyl (E)-2-[2-(2-methylphenoxy)-methyl]phenyl-2- (methoxyimido)acetate) and its metabolites as follows: (E)-2-[2-(2- methylphenoxy)methyl]-phenyl-2-(methoxyimido)acetic acid; (E)-2-[2-(2- hydroxymethylphenoxy)methyl]-phenyl-2-(methoxyimido)acetic acid (free and glucose conjugated); and (E)-2-[2-(4-hydroxy-2-methylphenoxy)- methyl]phenyl-2-(methoxyimido)acetic acid (free and glucose conjugated) in or on the following commodities: pome fruit at 0.5 ppm, grapes at 1.0 ppm, pecans, at 0.15 ppm, apple pomace at 1.0 ppm, and raisins at 1.5 ppm. Tolerances are established in or on meat byproducts of cattle, sheep and goats at 0.01 ppm for the metabolite [(E)-2-[2-(2- methylphenoxy)methyl]-phenyl-2-(methoxyimido)acetic acid] resulting from the use of the fungicide kresoxim-methyl.
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Objections and Hearing Requests
The new FFDCA section 408(g) provides essentially the same process for persons to ``object'' to a tolerance regulation as was provided in the old section 408 and in section 409. However, the period for filing objections is 60 days, rather than 30 days. EPA currently has procedural regulations which govern the submission of objections and hearing requests. These regulations will require some modification to reflect the new law. However, until those modifications can be made, EPA will continue to use those procedural regulations with appropriate adjustments to reflect the new law.
Any person may, by August 9, 1999, file written objections to any aspect of this regulation and may also request a hearing on those objections. Objections and hearing requests must be filedwith the Hearing Clerk, at the address given under the ``ADDRESSES'' section (40 CFR 178.20). A copy of the objections and/or hearing requests filed with the Hearing Clerk should be submitted to the OPP docket for this regulation. The objections submitted must specify the provisions of the regulation deemed objectionable and the grounds for the objections (40 CFR 178.25). Each objection must be accompanied by the fee prescribed by 40 CFR 180.33(i). 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 tolerance objection fee waivers, contact James Tompkins, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. Office location, telephone number, and e-mail address: Rm. 239, Crystal Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA, (703) 305-5697, tompkins.jim@epa.gov. Requests for waiver of tolerance objection fees should be sent to James Hollins, Information Resources and Services Division (7502C), Office of Pesticide Programs, Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
If a hearing is requested, the objections must include a statement of the factual issues on which a hearing is requested, the requestor's contentions on such issues, and a summary of any evidence relied upon by the requestor (40 CFR 178.27). A request for a hearing will be granted if the Administrator determines that the material submitted shows the following: There is 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 in the manner sought by the requestor would be adequate to justify the action requested (40 CFR 178.32). 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
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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.
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Public Record and Electronic Submissions
EPA has established a record for this regulation under docket control number [OPP-300873] (including any comments and data submitted electronically). A public version of this record, including printed, paper versions of electronic comments, which does not include any information claimed as CBI, is available for inspection from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The public record is located in Room 119 of the Public Information and Records Integrity Branch, Information Resources and Services Division (7502C), Office of Pesticide Programs, Environmental Protection Agency, Crystal Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
Objections and hearing requests may be sent by e-mail directly to EPA at:
opp-docket@epa.gov.
E-mailed objections and hearing requests must be submitted as an ASCII file avoiding the use of special characters and any form of encryption.
The official record for this regulation, as well as the public version, as described in this unit will be kept in paper form. Accordingly, EPA will transfer any copies of objections and hearing requests received electronically into printed, paper form as they are received and will place the paper copies in the official record which will also include all comments submitted directly in writing. The official record is the paper record maintained at the Virginia address in ``ADDRESSES'' at the beginning of this document.
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Regulatory Assessment Requirements
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Certain Acts and Executive Orders
This final rule establishes tolerances under section 408(d) of the FFDCA in response to a petition submitted to the Agency. The Office of Management and Budget (OMB) has exempted these types of actions from review under Executive Order 12866, entitled Regulatory Planning and Review (58 FR 51735, October 4, 1993). This final rule does not contain any information collections subject to OMB approval under the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose any enforceable duty or contain any unfunded mandate as described under Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). Nor does it require any prior consultation as specified by Executive Order 12875, entitled Enhancing the Intergovernmental Partnership (58 FR 58093, October 28, 1993), or 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 in accordance with Executive Order 13045, entitled Protection of Children from Environmental Health Risks and Safety Risks (62 FR 19885, April 23, 1997).
In addition, 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. Nevertheless, the Agency previously assessed whether establishing tolerances, exemptions from tolerances, raising tolerance levels or expanding exemptions might adversely impact small entities and concluded, as a generic matter, that there is no adverse economic impact. The factual basis for the Agency's generic certification for tolerance actions published on May 4, 1981 (46 FR 24950), and was provided to the Chief Counsel for Advocacy of the Small Business Administration.
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Executive Order 12875
Under Executive Order 12875, entitled Enhancing the Intergovernmental Partnership (58 FR 58093, October 28, 1993), EPA may not issue a regulation that is not required by statute and that creates a mandate upon a State, local or tribal government, unless the Federal government provides the funds necessary to pay the direct compliance costs incurred by those governments. If the mandate is unfunded, EPA must provide to OMB a description of the extent of EPA's prior consultation with representatives of affected State, local, and tribal governments, the nature of their concerns, copies of any written communications from the governments, and a statement supporting the need to issue the regulation. In addition, Executive Order 12875 requires EPA to develop an effective process permitting elected officials and other representatives of State, local, and tribal governments ``to provide meaningful and timely input in the development of regulatory proposals containing significant unfunded mandates.''
Today's rule does not create an unfunded Federal mandate on State, local, or tribal governments. The rule does not impose any enforceable duties on these entities. Accordingly, the requirements of section 1(a) of Executive Order 12875 do not apply to this rule.
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Executive Order 13084
Under Executive Order 13084, entitled Consultation and Coordination with Indian Tribal Governments (63 FR 27655, May 19, 1998), EPA may not issue a regulation that is not required by statute, that significantly or uniquely affects the communities of Indian tribal governments, and that imposes substantial direct compliance costs on those communities, unless the Federal government provides the funds necessary to pay the direct compliance costs incurred by the tribal governments. If the mandate is unfunded, EPA must provide OMB, in a separately identified section of the preamble to the rule, a description of the extent of EPA's prior consultation with representatives of affected tribal governments, a summary of the nature of their concerns, and a statement supporting the need to issue the regulation. In addition, Executive Order 13084 requires EPA to develop an effective process permitting elected officials and other representatives of Indian tribal governments ``to provide meaningful and timely input in the development of regulatory policies on matters that significantly or uniquely affect their communities.''
Today's rule does not significantly or uniquely affect the communities of Indian tribal governments. This action does not involve or impose any requirements that affect Indian tribes. Accordingly, the requirements of section 3(b) of Executive Order 13084 do not apply to this rule.
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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 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 the rule in
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the Federal Register. This rule is not a ``major rule'' as defined by 5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure, Agricultural commodities, Pesticides and pests, Reporting and recordkeeping requirements.
Dated: May 28, 1999.
Joseph J. Merenda, Jr.
Acting Director, Office of Pesticide Programs. Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
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The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), (346a), and 371.
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Section 180.554 is added to read as follows:
Sec. 180.554 Kresoxim-methyl; tolerances for residues.
(a) General. (1) Tolerances are established for the combined residues of the fungicide kresoxim-methyl (methyl (E)-2-[2-(2- methylphenoxy)-methyl]phenyl-2-(methoxyimido)acetate) and its metabolites as follows: (E)-2-[2-(2-methylphenoxy)methyl]-phenyl-2- (methoxyimido)acetic acid; (E)-2-[2-(2-hydroxymethylphenoxy)methyl]- phenyl-2-(methoxyimido)acetic acid (free and glucose conjugated); and (E)-2-[2-(4-hydroxy-2-methylphenoxy)-methyl]phenyl-2- (methoxyimido)acetic acid (free and glucose conjugated) in or on the following commodities:
Parts Commodity
per million
Apple, pomace.................................................. 1.0 Grapes......................................................... 1.0 Pecans......................................................... 0.15 Pome fruit..................................................... 0.5 Raisins........................................................ 1.5
(2) Tolerances are established in or on the following commodities for the residues of the metabolite (E)-2-[2-(2-methylphenoxy)methyl]- phenyl-2-(methoxyimido)acetic acid resulting from the use of the fungicide kresoxim-methyl:
Parts Commodity
per million
Cattle, meat byproducts........................................ 0.01 Goat, meat byproducts.......................................... 0.01 Sheep, meat byproducts......................................... 0.01
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 99-14761Filed6-9-99; 8:45 am]
BILLING CODE 6560-50-F
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