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

[Federal Register: January 12, 2000 (Volume 65, Number 8)]

[Rules and Regulations]

[Page 1790-1796]

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

[DOCID:fr12ja00-17]

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-300962; FRL-6485-4]

RIN 2070-AB78

Mepiquat Chloride; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

SUMMARY: This regulation establishes tolerances for mepiquat chloride regulated as N,N-dimethylpiperidinium chloride in or on grapes and raisins. 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 January 12, 2000. Objections and requests for hearings, identified by docket control number OPP-300962, must be received by EPA on or before March 13, 2000. 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-300962 in the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Cynthia Giles-Parker, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 401 M St., SW., Washington, DC 20460; telephone number: 703 305-7740; and e-mail address: giles- parker.cynthia@epa.gov.

SUPPLEMENTARY INFORMATION:

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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 Potentially Categories

      NAICS 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'' and then look up the entry for this document under the ``Federal Register--Environmental Documents.'' You can also go directly to the Federal Register listings at http://www.epa.gov/fedrgstr/.

      2. In person. The Agency has established an official record for this action under docket control number OPP-300962. 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 November 24, 1999 (64 FR 66181) (FRL- 6396-4), 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) for a tolerance by BASF Corporation. 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 180.384 be amended by establishing tolerances for residues of the plant growth regulator mepiquat chloride, in or on grapes at 1.0 parts per million (ppm), and raisins at 5.0 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 tolerances for residues of mepiquat chloride in or on grapes at 1.0 ppm, and raisins at 5.0 ppm. EPA's assessment of the dietary 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 results of the toxicity studies for mepiquat chloride are listed below.

      1. Subchronic toxicity study-- Rat. The no-observed-adverse- effect level (NOAEL) for males and females is 4,632 ppm (about 346 mg/kg/day) and the lowest-observed-adverse-effect level (LOAEL) for males and females is 12,000 ppm (about 889 mg/kg/day) based on tremors in all rats; decreased body weight gain, food consumption and food efficiency; increase in thromboplastin time; decrease in serum calcium, creatinine glucose, total protein, albumin, globulin and the triglycerides; reduced grip strength of forelimbs and hindlimbs in both sexes; prolonged reaction time in the hot-plate test on day 93 in males; decreased absolute weight of liver, kidneys and adrenals in males, and liver and adrenals in females; decreased relative weight of liver in males; and increased relative weight of kidneys and testes in males and of kidneys in females.

      2. Subchronic toxicity study-- dog. The LOAEL is 3,000 ppm (95.3 mg/kg/day), based on clinical signs of toxicity (slight sedation), body weight loss (up to 14%) and hematological effects (up to 14% reduction in hemoglobin content and number of erythrocytes and reduced hematocrit). The NOAEL is 1,000 ppm (32.4 mg/kg/day).

      3. Chronic toxicity study--rat. The NOAEL is 2,316 ppm (106 mg/kg/ day). The LOAEL is 5,790 ppm (268 mg/kg/day), based upon decreased body weights and body weight gains for both males and females, increases in urinary crystals for males, and pathological

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         changes in the adrenal cortex in females.

      4. Chronic toxicity Study-- dog. Study 1 and 2. The NOAEL is 1,800 ppm (58.4 mg/kg/day) and the LOAEL is 6,000 ppm (170 mg/kg/day), based on impaired neurological functions (slight sedation, abdominal/ lateral positioning, spasms, and salivation) and epithelial vacuolization of the renal distal tubules.

      5. Carcinogenicity study--rat. The LOAEL for males (269 mg/kg/day) and females (370 mg/kg/day) is 5,790 ppm, based upon decreased body weights, body weight gains, food consumption, food efficiency, and macroscopic and non-neoplastic findings. The NOAEL for males (105 mg/ kg/day) and females (141 mg/kg/day) is 2,316 ppm. There were no treatment-related neoplastic findings for males or females treated with mepiquat chloride. Thus, mepiquat chloride does not exhibit carcinogenic potential in a 2-year feeding study involving male and female, rats.

      6. Carcinogenicity study-- mice. The NOAEL for mepiquat chloride administered for 2 years in food is 7,500 ppm for male (1,140 mg/kg/ day) and female (1,348 mg/kg/day) B6C3F1 mice. There were no treatment- related neoplastic findings for males or females treated with mepiquat chloride. Thus, mepiquat chloride does not exhibit carcinogenic potential in a 2-year feeding study involving male and female B6C3F1 mice over this dose range. Based upon the lack of treatment-related findings, mepiquat chloride was not administered at the Maximum Tolerated Dose (MTD). However, the high dose (7,500 ppm) for the study was sufficient to assess carcinogenicity since the limit dose of 1,000 mg/kg/day was exceeded.

      7. Developmental toxicity study-- rat. Based on the clinical signs of toxicity and decreases in the food consumption and body weight gains, the maternal toxicity LOAEL is 300 mg/kg/day and the maternal toxicity NOAEL is 150 mg/kg/day. Since developmental toxicity was not observed in this study, the developmental NOAEL is greater than or equal to 300 mg/kg/day, the highest dose tested.

      8. Developmental toxicity study--. rabbit. The maternal LOAEL is 150 mg/kg body weight/day, based on reduced body weight gains and reduced food consumption. The maternal NOAEL is 100 mg/kg body weight/ day. The developmental LOAEL is 150 mg/kg/day, based on increased skeletal variations. The developmental NOAEL is 100 mg/kg/day.

      9. Reproductive toxicity study--two-generation--rat. The LOAEL for systemic toxicity is 5,000 ppm for male and female rats, based on neurological impairment, decreased body weight and body weight gain in the adults, and retarded growth of F1and F2 pups. This dose corresponds to dietary concentrations of 499.3 and 574.5 mg/kg/day, respectively, for F0and F1 males and 530.0 and 626.5 mg/kg/day, respectively, for F0 and F1females. The corresponding NOAEL is 1500 ppm. There were no treatment-related effects on reproductive parameters. The LOAEL for reproductive toxicity is greater than 5,000 ppm. This study did not establish a reproductive NOAEL; however, the systemic NOAEL of 1,500 ppm would also be regarded as the reproductive NOAEL.

      10. Reverse Gene Mutation Assay. Negative.

      11. Structural Chromosome Aberration Assay. Negative.

      12. Unscheduled DNA Synthesis Assay. Negative.

      13. Metabolism study. Mepiquat chloride did not accumulate in tissues of rats. Urine, feces and bile samples from various treatments were used for studies of the metabolic fate of mepiquat chloride. In all cases, only the unchanged compound could be detected. There was no biotransformation of mepiquat chloride in vivo. The potential metabolites, such as 1-methylpiperidine or piperidine, were not detected.

   2. Toxicological Endpoints

      The following endpoints were used in the risk assessments for mepiquat chloride.

      1. Acute toxicity. The endpoint for the acute dietary risk assessment was estimated, based on the 1-year dog feeding study with the 90-day dog feeding as a supporting study. The NOAEL was 58.4 mg/kg/ day, the Uncertainty Factor (UF) was 100, and the FQPA safety factor was reduced to 1X and applies to all population subgroups. The endpoints were impaired neurological functions (salivation, sedation, spasms, abdominal/lateral positioning), epithelial vacuolation of renal distal tubules, decrease in body weight, and hematology changes (decrease in RBC, hemoglobin, and hematocrit). The acute reference dose (aRfD) was 0.6 mg/kg/day. Since the FQPA safety factor was reduced to 1x the Acute Population Adjusted Dose (aPAD) was 0.6 mg/kg/day.

      2. Short- and intermediate-term toxicity. The oral NOAEL of 58.4 mg/kg/day from the combined chronic and subchronic toxicity studies in dogs was selected for the short- and intermediate-term dermal endpoint. The LOAEL was 95.3 mg/kg/day, based on clinical signs of toxicity (sedation, abdominal and lateral positions and tonic/clonic spasms), decreased body weight, and hematological changes. An oral dose was selected due to the lack of a dermal toxicity study. An UF of 100 was selected, based on 10x for interspecies extrapolation and 10x for intraspecies variability. The Dermal Absorption Factor (DAF) is 25%. The inhalation absorption factor is 100%..

      3. Chronic toxicity. The chronic dietary endpoint is the NOAEL of 58.4 mg/kg/day from the 1-year and the 90-day dog feeding studies for the general U.S. population. The LOAEL was 95.3 mg/kg/day, based on clinical signs of toxicity (sedation, abdominal and lateral positions and tonic/clonic spasms), decreased body weight, and hematological changes. An UF of 100 was selected, based on 10x for interspecies extrapolation and 10x for intraspecies variability. The chronic RfD, 0.6 mg/kg/day is the chronic NOAEL divided by the UF which equals 58.4 mg/kg/day divided by 100. Since the FQPA safety factor was reduced to 1x the chronic population adjusted dose (cPAD) equals 0.6 mg/kg/day.

      4. Carcinogenicity. Mepiquat chloride is classified as a ``not likely'' human carcinogen.

   3. Exposures and Risks

      1. From food and feed uses. Tolerances have been established (40 CFR 180.384) for the residues of mepiquat chloride, in or on cotton seed, cotton forage, meat, milk, poultry and eggs. Tolerances are proposed on grapes and raisins. Risk assessments were conducted by EPA to assess dietary exposures from mepiquat chloride as follows:

         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. The Dietary Exposure Evaluation Model (DEEM) detailed acute analysis estimates the distribution of single exposures for the overall U.S. population and certain subgroups. The analysis evaluates individual food consumption as reported by respondents in the USDA 1989-1992 Continuing Survey of Food Intake by Individuals (CSFII) and accumulates exposure to the chemical for each commodity. Each analysis assumes uniform distribution of mepiquat chloride in the commodity supply.

         A Tier 1 (assumptions: tolerance level residues and 100 percent crop treated,) acute dietary risk assessment was

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         conducted via DEEM. The DEEM processing factor was set at 1.00for grape juice, based on the lack of concentration of residues therein; the default ratio of 3.0 was applied to grape juice concentrate. The commodities included in the acute DEEM analysis were: cottonseed (meal, oil); grapes (grapes, juice, juice concentrate, leaves, raisins, wine and sherry); and, the meat, fat, and meat by-products of cattle, goats, hogs, horses (meat only), and swine. Milk, egg, and poultry tolerances were not included, as these have recently been revoked, based upon the Regegistration Eligibility Determinations that the data indicate no finite residues are likely to occur in these commodities (40 CFR 180.6a(3)).

         The resulting dietary food exposures (95th percentile) occupy up to 1.5% of the aPAD for the most highly exposed population subgroup (Children 1-6 years). These results should be viewed as conservative, health protective risk estimates. Refinements such as taking into account that only two grape varieties are to be treated; the percent- treated of their market share; and, Monte Carlo analysis, would yield even lower estimates of acute dietary exposure.

         ii. Chronic exposure and risk. A Tier 1, chronic dietary risk assessment was conducted via DEEM. The DEEM processing factor settings for grape juice (1.0) and grape juice concentrate (3.0), and the commodities included in the chronic DEEM analysis, were exactly the same as those included in the acute DEEM analysis.

         The resulting dietary food exposures occupy up to 0.3% of the cPAD for the most highly exposed population subgroup (Children 1-6 years). These results should be viewed as conservative, health protective risk estimates. Refinements such as taking into account that only two grape varieties are to be treated; the percent-treated of their market share; and, anticipated residues would yield even lower estimates of chronic dietary exposure.

         iii. Cancer dietary risk from food sources. Mepiquat chloride was classified as a ``not likely human carcinogen.'' Therefore, a cancer risk assessment was not conducted.

      2. From drinking water. EPA does not have monitoring data available to perform a quantitative drinking water risk assessment for mepiquat chloride. In the absence of reliable, available monitoring data, EPA uses models which incorporate chemical-specific data on the characteristics in question to estimate concentrations of pesticides in ground and surface water. A drinking water estimate for mepiquat chloride in ground water was generated by the screening concentratin in ground water (SCI-GROW) model. Conservative assumptions were built into the ground water scenario used by the SCI-GROW model, such as assuming shallow ground water, coarse soils and high levels of irrigation. The estimate from SCI-GROW (0.004 parts per billion (ppb)) represents an upper bound on the concentration of mepiquat chloride in ground waters as a result of agricultural use.

         Estimates of concentrations of mepiquat chloride in surface water were made using the generic expected environmental concentration (GENEEC) model. The peak estimate for mepiquat chloride using the GENEEC model is 1.86 ppb. The 56-day average for mepiquat chloride is 1.06 ppb.

         A Drinking Water Level of Comparison (DWLOC) is a theoretical upper limit of a pesticide's concentration in drinking water in light of total aggregate exposure to that pesticide in food and through residential uses. A DWLOC will vary depending on the toxic endpoint, consumption and body weight. Different populations will have different DWLOCs. EPA uses DWLOCs internally in the risk assessment process as a surrogate measure of potential exposure associated with pesticide exposure through drinking water. In the absence of monitoring data for pesticides, the DWLOC is used as a point of comparison against conservative model estimates of potential pesticide concentration in water. DWLOC values are not regulatory standards for drinking water. EPA has calculated DWLOCs for acute and chronic (non-cancer) exposure to mepiquat chloride for the U.S. population and selected subgroups.

         The DWLOCs for acute and chronic risk range from 6,000 ppb for infants and children to 21,000 ppb for the U.S. population. The estimated concentration of mepiquat chloride in ground water is 0.004 ppb and 1.86 ppb in surface water, which are less than the DWLOCs as a contribution to acute and chronic exposure. The estimated concentrations of mepiquat chloride in ground and surface water are considered conservative estimates. Therefore, EPA concludes with reasonable certainty that residues of mepiquat chloride in food and drinking water would not result in an unacceptable estimate of acute or chronic (non-cancer) aggregate human health risk.

      3. 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 mepiquat chloride 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, mepiquat chloride 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 mepiquat chloride has a common mechanism of toxicity with other substances. For information regarding EPA 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. Aggregate Risks and Determination of Safety for U.S. Population

      1. Acute risk. The acute aggregate risk is the sum of exposures resulting from acute dietary food and acute dietary drinking water. This acute aggregate risk assessment was conducted for all population subgroups, and the aPAD (0.6 mg/kg/day) was applied in determining exposures to all population subgroups. The Estimated Environmental Concentrations (EEC) for assessing acute aggregate dietary risk are 0.004 ppb (in ground water, based on SCI-GROW) and 1.9 ppb (in surface water, based on the GENEEC peak value). The back-calculated DWLOCs for assessing acute aggregate dietary risk range from 6,000 ppb for the most highly exposed population subgroup (Non-nursing infants, 00-362Filed1-11-00; 8:45 am] BILLING CODE 6560-50-F