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Norflurazon. August 30, 1995. Pesticide Tolerance. Proposed Rule. Federal Register

http://www.epa.gov/docs/fedrgstr/EPA-PEST/1995/August/Day-30/pr-387.html

ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180

[PP 4E4383/P627; FRL-4970-9]
RIN 2070-AC18

Norflurazon; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

SUMMARY: EPA proposes to establish a tolerance for combined residues of the herbicide norflurazon and its desmethyl metabolite in or on the raw agricultural commodity caneberries. The Interregional Research Project No. 4 (IR-4) submitted a petition requesting the proposed regulation to establish a maximum permissible level for residues of norflurazon.

DATES: Comments, identified by the document control number [PP 4E4383/ P627], must be received on or before September 29, 1995.

ADDRESSES: By mail, submit written comments to: Public Response and Program Resources Branch, Field Operations Division (7506C), Office of Pesticide Programs, Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. In person, bring comments to: Rm. 1132, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA 22202. Comments and data may also be submitted to OPP by sending electronic mail (e-mail) to: opp-docket@epamail.epa.gov
Electronic comments must be submitted as an ASCII file avoiding the use of special characters and any form of encryption. Comments and data will also be accepted on disks in WordPerfect 5.1 file format or ASCII file format. All comments and data in electronic form must be identified by the docket number [PP 4E4383/P627]. Electronic comments on this proposed rule may be filed online at many Federal Depository Libraries. Additional information on electronic submissions

[[Page 45114]]
can be found in the ``SUPPLEMENTARY INFORMATION'' section of this document.
Information submitted as a comment concerning this document may be claimed confidential by marking any part or all of that information as ``Confidential Business Information.'' CBI should not be submitted through e-mail. Information marked as CBI will not be disclosed except in accordance with procedures set forth in 40 CFR part 2. A copy of the comment 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. All written comments will be available for public inspection in Rm. 1132 at the address given above, from 8 a.m. to 4:30 p.m., Monday through Friday, excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: By mail: Hoyt L. Jamerson, Registration Division (7505W), Office of Pesticide Programs, Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. Office location and telephone number: Sixth Floor, Crystal Station #1, 2800 Jefferson Davis Hwy., Arlington, VA 22202, (703)-308-8783; e-mail: jamerson.hoyt@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: The Interregional Research Project No. 4 (IR-4), New Jersey Agricultural Experiment Station, P.O. Box 231, Rutgers University, New Brunswick, NJ 08903, has submitted pesticide petition (PP 4E4383) to EPA on behalf of the IR-4 Agricultural Experiment Stations of Virginia and Washington. This petition requests that the Administrator, pursuant to section 408(e) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(e), amend 40 CFR 180.356 by establishing a tolerance for residues of the herbicide norflurazon (4-chloro-5-(methylamino)-2-(alpha, alpha, alpha-trifluro-m-tolyl)-3- (2H) pyridazinone) and its desmethyl metabolite ((4-chloro-5-(amino)-2- alpha, alpha, alpha-trifluro-m-tolyl)-3(2H)-pyridazinone) in or on the raw agricultural commodity caneberries at 0.2 part per million (ppm). Caneberries are defined for tolerance purposes to include blackberries, loganberry, raspberries, and varieties and/or hybrids of these. Tolerances are already established for the combined residues of norflurazon and its desmethyl metabolite in or on blackberries at 0.1 ppm and raspberries at 0.2 ppm.
The scientific data submitted in the petition and other relevant material have been evaluated. The toxicological data considered in support of the proposed tolerance include:

1. Acute oral and dermal toxicity studies were performed, placing technical norflurazon in toxicity Category IV and Category III for primary eye irritation.
   
2. A 6-month feeding study with dogs fed diets containing 0, 50, 150, or 450 ppm (equivalent to 0, 1.53, 5.02, or 14.27 milligrams (mg)/ kilogram (kg)/day for males; 0, 1.58, 4.77, or 17.75 mg/kg/day for females) with a no-observed-effect level (NOEL) of 50 ppm, based on increased absolute and relative liver weight and increased cholesterol in both sexes at the 150-ppm dose level.
3. A developmental toxicity study in rats given oral gavage doses of 0, 100, 200, or 400 mg/kg/day with a NOEL for maternal toxicity of less than 100 mg/kg/day based on decreased body weight gain. The NOEL for developmental toxicity was established at 400 mg/kg/day. Developmental toxicity was suggested at the 400-mg/kg/day dose level in the form of an increase in bipartite thoracic vertebrae and an increase in rudimentary 14th ribs. These effects are believed to be secondary to the maternal effects observed at the 400-mg/kg/day dose level.
4. A developmental toxicity study in rabbits given oral gavage doses of 0, 10, 30, or 60 mg/kg/day with a NOEL for maternal toxicity of 30 mg/kg/day based on clinical toxicity and reduced body weight gain at the 60-mg/kg/day dose level. The NOEL for developmental toxicity was established at 30 mg/kg/day based on a statistical increase in skeletal variations at the 60-mg/kg/day dose level.
5. A three-generation reproduction study in rats fed diets containing 0, 125, 375, or 1,025 ppm (equivalent to 0, 6.25, 18.75. or 51.25 mg/kg/day) with a NOEL for reproductive toxicity of 1,025 ppm. There were no apparent effects on reproductive performance in this study.
   
6. A carcinogenicity study in rats fed diets containing 0, 125, 375, or 1,025 ppm (equivalent to 0, 6.25, 18.75, or 51.25 mg/kg/day) with a NOEL of 375 ppm and a lowest-effect-level (LEL) of 1,025 ppm based on increased kidney weight and accompanying microscopic pathologic changes, as well as an increase in liver weight in male and female rats, and an increase in thyroid weight in males. There were no carcinogenic effects attributable to norflurazon observed under the conditions of the study.
   
7. A carcinogenicity study in mice fed diets containing 0, 85, 340, or 1,360 ppm (equivalent to 0, 12.8, 58.7, or 218.8 mg/kg/day) with a NOEL for systemic effects of 85 ppm for male mice and 340 ppm for female mice. The LEL is established at 340 ppm for male mice based on the increased incidence of enlarged spleen, increased absolute and relative liver weight, and increased incidence of nephritis. The LEL for female mice is established at 1,360 ppm based on the increased incidence of enlarged liver and cystic ovaries, the increased absolute and relative liver weight, and the increased incidence of pyelonephritis, a significant positive trend in hepatocellular adenomas and in combined hepatocellular adenomas and/or carcinomas. A significant pairwise increase in hepatocellular adenomas and hepatocellular adenomas/carcinomas combined was observed at the 204 mg/ kg/day dose level in males. There were no statistically significant increases in tumor incidence with incremental doses of norflurazon in females.
   
8. Mutagenicity assays including an in-vitro cytogenetic assay in Chinese hamster ovary cells for chromosome aberrations, negative; and an unscheduled DNA synthesis test in primary rat hepatocytes for DNA repair, negative for potential mutagenic activity.
9. In a rat metabolism study norflurazon was rapidly absorbed from the gastrointestinal tract and extensively metabolized. Based on a weight-of-the evidence determination, EPA has classified norflurazon as a possible human carcinogen (Group C). This classification is based on the presence of benign tumors in only one sex of one species at one dose level, adequate but negative mutagenicity studies, and no finding of carcinogenicity in structurally related compounds. EPA has determined that for purposes of risk characterization the reference dose (RfD) should be used to quantify dietary risk.
   Dietary risk assessments for norflurazon indicate that there is minimal risk from established tolerances and the proposed tolerance for caneberries. Dietary risk assessments for the herbicide were conducted using the Reference Dose (RfD) to assess chronic exposure and risk and the Margin of Exposure (MOE) for acute toxicity. The RfD is calculated at 0.02 mg/kg/of body weight/day based on a NOEL of 1.53 mg/kg/day from the 6-month dog feeding study and an uncertainty factor of 100. The theoretical maximum residue contribution (TMRC) from existing tolerances and the proposed tolerance for caneberries utilize 10 percent of the RfD for the general population and 47 percent of the RfD for [[Page 45115]]
   nonnursing infants less than 1-year in age. The MOE is a measure of how closely the high-end acute dietary exposure comes to the no-observed-effect (NOEL) level from the toxicity endpoint of concern. For norflurazon the MOE was calculated as a ratio of the NOEL (30 mg/kg/day) from the rabbit developmental toxicity study to dietary exposure, as estimated for the population subgroup at greatest risk (females of child-bearing age). The MOE for this subgroup is estimated at 5,000 for high-end exposure. Acute dietary margins of exposure of less than 100 are generally of concern to EPA. A MOE of 5,000 poses minimal risk.
   The nature of the residues in caneberries is adequately understood for the purposes of the proposed tolerance. An adequate analytical method is available for enforcement purposes. Because of the long lead time from establishing these tolerances to publication of the enforcement method in the Pesticide Analytical Manual, Volume II, the analytical method is being made available to anyone with an interest in pesticide enforcement when requested from: Calvin Furlow, Public Response and Program Resources Branch, Field Operations Division (7506C), Office of Pesticide Programs, Environmental Protections Agency, 401 M St., SW., Washington, DC 20460. Office location and telephone number: Rm. 1132, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA 22202, (703)-305-5937.
   No secondary residues are expected in meat, milk, poultry, or eggs since caneberries are not considered a livestock feed commodity. There are currently no actions pending against the continued registration of this chemical.
   Based on the information and data considered, the Agency has determined that the tolerance established by amending 40 CFR part 180 would protect the public health. Therefore, it is proposed that the tolerance be established as set forth below. Any person who has registered or submitted an application for registration of a pesticide, under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) as amended, which contains any of the ingredients listed herein, may request within 30 days after publication of this notice in the Federal Register that this rulemaking proposal be referred to an Advisory Committee in accordance with section 408(e) of the FFDCA.
   A record has been established for this rulemaking under docket number [PP 4E4383/P627] (including comments and data submitted electronically as described below). 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 a.m. to 4:30 p.m., Monday through Friday, excluding legal holidays. The public record is located in Rm. 1132 of the Public Response and Program Resources Branch, Field Operations Division (7506C), Office of Pesticide Programs, Environmental Protection Agency, Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA. Electronic comments can be sent directly to EPA at: opp-Docket@epamail.epa.gov
   Electronic comments must be submitted as an ASCII file avoiding the use of special characters and any form of encryption. The official record for this rulemaking, as well as the public version, as described above will be kept in paper form. Accordingly, EPA will transfer all comments received electronically into printed, paper form as they are received and will place the paper copies in the official rulemaking record which will also include all comments submitted directly in writing. The official rulemaking record is the paper record maintained at the address in ``ADDRESSES'' at the beginning of this document.
   Under Executive Order 12866 (58 FR 51735, Oct. 4, 1993), the Agency must determine whether the regulatory action is ``significant'' and therefore subject to all the requirements of the Executive Order (i.e., Regulatory Impact Analysis, review by the Office of Management and Budget (OMB)). Under section 3(f), the order defines ``significant'' as those actions likely to lead to a rule (1) having an annual effect on the economy of $100 million or more, or adversely and materially affecting a sector of the economy, productivity, competition, jobs, the environment, public health or safety, or State, local or tribal governments or communities (also known as ``economically significant''); (2) creating serious inconsistency or otherwise interfering with an action taken or planned by another agency; (3) materially altering the budgetary impacts of entitlement, grants, user fees, or loan programs; or (4) raising novel legal or policy issues arising out of legal mandates, the President's priorities, or the principles set forth in this Executive Order. Pursuant to the terms of this Executive Order, EPA has determined that this rule is not ``significant'' and is therefore not subject to OMB review.
   Pursuant to the requirements of the Regulatory Flexibility Act (Pub. L. 96-354, 94 Stat. 1164, 5 U.S.C. 601-612), the Administrator has determined that regulations establishing new tolerances or raising tolerance levels or establishing exemptions from tolerance requirements do not have a significant economic impact on a substantial number of small entities. A certification statement to this effect was published in the Federal Register of May 4, 1981 (46 FR 24950).

   List of Subjects in 40 CFR Part 180

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

   Dated: August 11, 1995.

   Stephen L. Johnson,
   Director, Registration Division, Office of Pesticide Programs.

   Therefore, it is proposed that 40 CFR part 180 be amended as follows:

   PART 180--[AMENDED]

   1. The authority citation for part 180 continues to read as follows: Authority: 21 U.S.C. 346a and 371.

      Sec. 180.356 [Amended]

      2. In Sec. 180.356 Norflurazon; tolerances for residues by amending the table therein by adding and alphabetically inserting an entry for caneberries at 0.2 part per million (ppm) and by removing the entries for blackberries and raspberries.

      [FR Doc. 95-21516 Filed 8-29-95; 8:45 am] BILLING CODE 6560-50-F