-------------------------------------------------------------------------- ENVIRONMENTAL PROTECTION AGENCY [PF-688; FRL-5582-6] Interregional Research Project Number 4; Pesticide Tolerance Petitions Filing AGENCY: Environmental Protection Agency (EPA). -------------------------------------------------------------------------- SUMMARY: This notice announces the filing of amendments to pesticide petitions 0E3909, 2E4052, 2E4065, 2E4092, and 3E4162. These amendments propose to extend the effective date for time-limited tolerances established for the combined residues of the herbicide 2-[1- (ethoxyimino)butyl]-5-[2-(ethylthio)propyl]-3- hydroxy-2-cyclohexen-1- one (also referred to in this document as sethoxydim) and its metabolites in or on various raw agricultural commodities. This notice contains a summary of the amended petition prepared by BASF Corporation (BASF) and submitted by the Interregional Research Project Number 4 (IR-4), the petitioner. DATES: Comments, identified by the docket number [PF-688; FRL-5582-6], must be received on or before February 7, 1997. 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 Highway, Arlington, VA 22202. Comments and data may also be submitted electronically by sending electronic mail (e- mail) to: email@example.com. Electronic comments on this notice may also be filed online at many Federal Depository Libraries. Information submitted as comments concerning this document may be claimed confidential by marking any part or all of that information as Confidential Business Information (CBI). 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 8:30 a.m. to 4:00 p.m., Monday through Friday, excluding legal holidays. Comments and data may also be submitted electronically 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 in 5.1 file format or ASCII file format. All comments and data in electronic form must be identified by the docket number PF-688. No CBI should be submitted through e- mail. Electronic comments on this proposed rule may be filed online at many Federal Depository Libraries. Additional information on electronic submissions can be found in Unit III of this document. 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 Highway, Arlington, VA 22202, (703) 308-8783, e- mail:firstname.lastname@example.org. SUPPLEMENTARY INFORMATION: EPA has received amendments to pesticide petitions 0E3909, 2E4052, 2E4065, 2E4092, and 3E4162 from the Interregional Research Project No. 4 (IR-4), New Jersey Agricultural Experiment Station, P.O. Box 231, Rutgers University, New Brunswick, NJ 08903. These amendments propose, pursuant to section 408 of the Federal Food, Drug and Cosmetic Act (FFDCA), 21 U.S.C. 346a, to amend 40 CFR part 180 by extending the effective date to expire on December 31, 1998, for time-limited tolerances established for residues of the herbicide 2-[1-(ethoxyimino)butyl]-5-[2-(ethylthio)propyl]-3- hydroxy-2- cyclohexen-1-one) and its metabolites containing the 2-cyclohexen- 1-one moiety (calculated as the herbicide) in or on asparagus at 4.0 parts per million (ppm), carrot at 1.0 ppm, cranberry and endive at 2.0 ppm, and peppermint and spearmint at 30 ppm. Registration for use of sethoxydim on endive is limited to Florida based on the geographical representation of the residue data submitted. Additional residue data will be required to expand the area of usage. Persons seeking geographically broader registration should contact the Agency's Registration Division at the address provided above. EPA has determined that the amendment contains data or information regarding the elements set forth in section 408(d)(2); however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition. The nature of the residue is adequately understood, and practical and adequate analytical methods are available for enforcement purposes. Enforcement methods for sethoxydim are listed in the Pesticide Analytical Manual, Volume II (PAM II). Enforcement methods have also been submitted to the Food and Drug Administration for publication in PAM II. As required by section 408(d) of the FFDCA, as recently amended by the Food Quality Protection Act, IR-4 submitted a summary of amendments to the pesticide petitions and authorization for the summary to be published in the Federal Register in a notice of receipt of the petition. The summary was prepared by and represents the views of BASF; EPA, as mentioned above, is in the process of evaluating the petition. As required by section 408(d)(3) EPA is including the summary as a part of this notice of filing. EPA may have made minor edits to the summary for the purpose of clarity. I. Petition Summary A. Toxicological Profile 1. Data summary. A summary of toxicological studies for sethoxydim follows: i. A 1-year feeding study with dogs fed diets containing 0, 8.86/ 9.41, 17.5/19.9, and 110/129 milligrams (mg)/kilogram (kg)/day (males/ females) with a no-observed-effect-level (NOEL) of 8.86/9.41 mg/kg/day (males/females) based on equivocal anemia in male dogs at the 17.5-mg/ kg/day dose level. ii. A 2-year chronic feeding/carcinogenicity study with mice fed diets containing 0, 40, 120, 360, and 1,080 ppm (equivalent to 0, 6, 18, 54, and 162 mg/kg/day) with a systemic NOEL of 120 ppm (18 mg/kg/ day) based on non- neoplastic liver lesions in male mice at the 360 ppm (54 mg/kg/day) dose level. There were no carcinogenic effects observed under the conditions of the study. The maximum tolerated dose (MTD) was not achieved in female mice. iii. A 2-year chronic feeding/carcinogenic study with rats fed diets containing 0, 2, 6, and 18 mg/kg/day with a systemic NOEL greater than or equal to 18 mg/kg/day (highest dose tested). There were no carcinogenic effects observed under the conditions of the study. This study was reviewed under current guidelines and was found to be unacceptable because the doses used were insufficient to induce a toxic response and an MTD was not achieved. iv. A second chronic feeding/carcinogenic study with rats fed diets containing 0, 360, and 1,080 ppm (equivalent to 18.2/23.0, and 55.9/ 71.8 mg/kg/day (males/females). The dose levels were too low to elicit a toxic response in the test animals and failed to achieve an MTD or define a lowest effect level (LEL). Slight decreases in body weight in rats at the 1,080-ppm dose level, although not biologically significant, support a free-standing no- observed-adverse-effect-level (NOAEL) of 1,080 ppm (55.9/71.8 mg/kg/day (males/females)). There were no carcinogenic effects observed under the conditions of the study. v. A developmental toxicity study in rats fed dosages of 0, 50, 180, 650, and 1,000 mg/kg/day with a maternal NOAEL of 180 mg/kg/day and a maternal LEL of 650 mg/kg/day (irregular gait, decreased activity, excessive salivation, and anogenital staining); and a developmental NOAEL of 180 mg/kg/day and a developmental LEL of 650 mg/ kg/day (21 to 22 percent decrease in fetal weights, filamentous tail, and lack of tail due to the absence of sacral and/or caudal vertebrae, and delayed ossification in the hyoids, vertebral centrum and/or transverse processes, sternebrae and/or metatarsals, and pubes). vi. A developmental toxicity study in rabbits fed doses of 0, 80, 160, 320, and 400 mg/kg/day with a maternal NOEL of 320 mg/kg/day and a maternal LOEL of 400 mg/kg/day (37 percent reduction in body weight gain without significant differences in group mean body weights and decreased food consumption during dosing); and a developmental NOEL greater than 400 mg/kg/day (highest dose tested). vii. A 2-generation reproduction study with rats fed diets containing 0, 150, 600, and 3,000 ppm (approximately 0, 7.5, 30, and 150 mg/kg/day) with no reproductive effects observed under the conditions of the study. viii. Mutagenicity studies including: Ames assays were negative for gene mutation in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, with and without metabolic activity; a Chinese hamster bone marrow cytogenetic assay was negative for structural chromosomal aberrations at doses up to 5,000 mg/kg in Chinese hamster bone marrow cells in vivo; and recombinant assays and forward mutations tests in Bacillus subtilis, Escherichia coli, and S. typhimurium were all negative for genotoxic effects at concentrations of greater than or equal to 100 percent. ix. In a rat metabolism study, excretion was extremely rapid and tissue accumulation was negligible. 2. Chronic toxicity. Based on the available chronic toxicity data, EPA has established the Reference Dose (RfD) for sethoxydim at 0.09 milligrams (mg)/kilogram (kg) bw/day. The RfD for sethoxydim is based on a 1-year feeding study in dogs with a threshold no-observed effect level (NOEL) of 8.86 mg/kg/day and an uncertainty factor of 100. 3. Acute toxicity. Based on the available acute toxicity data, sethoxydim does not pose any acute dietary risks. Several acute toxicology studies place technical sethoxydim in acute toxicity category IV for primary eye and dermal irritation and acute toxicity category III for acute oral, dermal, and inhalation. The dermal sensitization-guinea pig study was waived because no sensitization was seen in guinea pigs dosed with the end-use product Poast (18 percent active ingredient). 4. Carcinogenicity. These tolerances were established as time- limited tolerances since an acceptable carcinogenicity study is needed in one rodent species. A repeat chronic feeding/carcinogenicity study in rats was submitted to EPA in November of 1995 and is awaiting review. The Agency will reassess sethoxydim tolerances based on the outcome of the rat chronic feeding/carcinogenicity study and, if appropriate, will establish permanent tolerances for asparagus, carrot, cranberry, endive, peppermint and spearmint. In the interim, there is little risk from the proposed time extension for these uses of sethoxydim, since available studies in rats and mice indicate no carcinogenic effects, there are adequate data to establish a RfD, existing tolerances (including these time-limited tolerances) do not exceed the RfD, and the tolerances for asparagus, carrot, cranberry, endive, and mint utilize less than 1 percent of the Reference Dose. Thus a cancer risk assessment is not necessary. B. Aggregate Exposure For purposes of assessing the potential dietary exposure, BASF has estimated aggregate exposure based on the Theoretical Maximum Residue Contribution (TMRC) from the tolerances of sethoxydim on: asparagus at 4.0 ppm, carrot at 1.0 ppm, cranberry and endive at 2.0 ppm, and peppermint and spearmint at 30.0 ppm. (The TMRC is a "worst case" estimate of dietary exposure since it is assumed that 100 percent of all crops for which tolerances are established are treated and that pesticide residues are at the tolerance levels.) The TMRC from existing tolerances for the overall U.S. population is estimated at 0.0311961 mg/kg bw/day, or 36 percent of the RfD. Dietary exposure to residues of sethoxydim in or on asparagus, carrot, cranberry, endive and mint increases the TMRC by 0.000701 mg/kg bw/day and accounts for less than 1 percent of the RfD for the overall U.S. population. EPA estimates indicate that dietary exposures will not exceed the RfD for any population subgroup for which EPA has data [See Proposed Rule at 60 FR 13941, March 15, 1995]. This exposure assessment relies on very conservative assumptions--100 percent of crops will contain sethoxydim residues and those residues would be at the level of the tolerance which results in an overestimate of human exposure. Other potential sources of exposure of the general population to residues of pesticides are residues in drinking water and exposure from non-occupational sources. Based on the available studies used in EPA's assessment of environmental risk, BASF does not anticipate exposure to residues of sethoxydim in drinking water. There is no established Maximum Concentration Level (MCL) for residues of sethoxydim in drinking water under the Safe Drinking Water Act (SDWA). EPA has not estimated non-occupational exposure for sethoxydim. Sethoxydim is labeled for use by homeowners on the following use sites: flowers, evergreens, shrubs, trees, fruits, vegetables, ornamental ground covers, and bedding plants. Hence, the potential for non- occupational exposure to the general population exists. However, these use sites do not appreciably increase exposure. Protective clothing requirements, including the use of gloves, adequately protect homeowners when applying the product. The product may only be applied through hose-end sprayers or tank sprayers as a 0.14% solution. Sethoxydim is not a volatile compound so inhalation exposure during and after application would be negligible. Dermal exposure would be minimal in light of the protective clothing and the low application rate. Post- treatment (re- entry) exposure would be negligible for these use sites as contact with treated surfaces would be low. Dietary risks from treated food crops are already adequately regulated by the established tolerances. The additional uses endive, asparagus , carrots, cranberries, peppermint, and spearmint will not increase the non- occupational exposure appreciably, if at all. Thus, BASF believes that the potential for non-occupational exposure to the general population is insignificant. BASF also considered the potential for cumulative effects of sethoxydim and other substances that have a common mechanism of toxicity. BASF is aware of one other active ingredient which is structurally similar, clethodim. However, BASF believes that consideration of a common mechanism of toxicity is not appropriate at this time. BASF does not have any reliable information to indicate that toxic effects produced by sethoxydim would be cumulative with clethodim or any other chemical; thus, BASF is considering only the potential risks of sethoxydim in its exposure assessment. C. Determination of Safety for U.S. Population Reference Dose (RfD). Using the conservative exposure assumptions described above, based on the completeness and the reliability of the toxicity data, EPA has estimated that aggregate exposure to sethoxydim will utilize 37 percent of the RfD for the U.S. population. EPA generally has no concern for exposures below 100 percent of the RfD. Therefore, based on the completeness and reliability of the toxicity data, and the conservative exposure assessment, BASF concludes that there is a reasonable certainty that no harm will result from aggregate exposure to residues of sethoxydim, including all anticipated dietary exposure and all other non-occupational exposures. D. Determination of Safety for Infants and Children 1. Developmental toxicity. Developmental toxicity was observed in a developmental toxicity study using rats but was not seen in a developmental toxicity study using rabbits. A developmental NOAEL of 180 mg/kg/day and developmental LEL of 650 mg/kg/day were established for the rat study. Effects noted in the rat study included decrease in fetal weights (21 to 22 percent), filamentous tail, lack of tail (due to absence of sacral and/or caudal vertebrae), and delayed ossification (hyoids, vertebral centrum and/or transverse processes, sternebrae and/ or metatarsals, and pubes). The developmental NOEL for the rabbit study was greater than 400 mg/kg/day and was the highest dose tested. The developmental effects observed in the rat study are believed to be secondary effects resulting from maternal stress. 2. Reproductive toxicity. A two-generation reproduction study with rats fed diets containing 0, 150, 600, and 3,000 ppm (approximately 0, 7.5, 30, and 150 mg/kg/day) produced no reproductive effects during the course of the study. Although the dose levels were insufficient to elicit a toxic response, the Agency has considered this study usable for regulatory purposes and has established a free-standing NOEL of 3,000 ppm (approximately 150 mg/kg/day) [See Proposed Rule at 60 FR 13941, March 15, 1995]. RFD. Based on the demonstrated lack of significant developmental or reproductive toxicity BASF believes that the RfD used to assess safety to children should be the same as that for the general population, 0.09 mg/kg/day. Using the conservative exposure assumptions described above, BASF has concluded that the most sensitive child population is that of children ages 1 to 6. BASF calculates the exposure to this group to be less than 70 percent of the RfD for all uses (including those proposed in this document). The proposed tolerances in endive, asparagus, carrot, cranberry, peppermint and spearmint represent an exposure to this group of less than 1 percent. Based on the completeness and reliability of the toxicity data and the conservative exposure assessment, BASF concludes that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the residues of sethoxydim, including dietary exposure and all other non- occupational exposures. 3. Endocrine effects. No special studies investigating potential estrogenic or endocrine effects of sethoxydim have been conducted. However, the standard battery of required studies has been completed. These studies include an evaluation of the potential effects on reproduction and development, and an evaluation of the pathology of the endocrine organs following repeated or long-term exposure. These studies are generally considered to be sufficient to detect any endocrine effects but no such effects were noted in any of the studies. II. Other Considerations There is no reasonable expectation that secondary residues will occur in milk, eggs, or meat of livestock and poultry from the proposed uses of sethoxydim on asparagus, cranberries, endive, and mint; there are no livestock feed commodities associated with these commodities. Any secondary residues occurring in meat, fat, meat byproducts and milk of cattle, goats, hogs, horses and sheep from the proposed use on carrots will be covered by existing tolerances. There are no residues expected to occur in poultry byproducts, fat or eggs since carrots are not considered a poultry feed item. There are no Codex maximum residue levels established for residues of sethoxydim on asparagus, carrots, cranberry, endive, or mint. III. Public Record EPA invites interested persons to submit comments on this notice of filing. Comments must bear a notation indicating the docket number, [PF-688; FRL-5582- 6]. All written comments filed in response to this petition will be available in the Public Response and Program Resources Branch, at the address given above from 8:30 a.m. to 4:00 p.m., Monday through Friday, except legal holidays. A record has been established for this rulemaking under docket number [PF-688; FRL-5582-6] (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 8:30 a.m. to 4:00 p.m., Monday through Friday, excluding legal holidays. The public record is located in Room 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: email@example.com 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 notice of filing, 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. List of Subjects Environmental protection, Administrative practice and procedure, Agricultural commodities, Pesticides and pests, Reporting and recordkeeping. Authority: 21 U.S.C. 346a. Dated: December 31, 1996. Stephen L. Johnson, Director Registration Division Office of Pesticide Programs [FR Doc. 97-415 Filed 1-7-97; 8:45 am]
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