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Cyfluthrin (IR-4). April 15, 1998. Pesticide Tolerance Petition. Federal Register
http://www.epa.gov/fedrgstr/EPA-PEST/1998/April/Day-15/p9395.htm
[Federal Register: April 15, 1998 (Volume 63, Number 72)] [Notices] [Page 18411-18420] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr15ap98-90] [[Page 18411]] ----------------------------------------------------------------------- ENVIRONMENTAL PROTECTION AGENCY [PF-801; FRL-5781-9] Notice of Filing of Pesticide Petitions AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. ----------------------------------------------------------------------- SUMMARY: This notice announces the initial filing of pesticide petitions proposing the establishment of regulations for residues of certain pesticide chemicals in or on various food commodities. DATES: Comments, identified by the docket control number PF-801, must be received on or before May 15, 1998. ADDRESSES: By mail submit written comments to: Public Information and Records Integrity Branch, Information Resources and Services Division (7502C), Office of Pesticides Programs, Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. In person bring comments to: Rm. 119FF, CM #2, 1921 Jefferson Davis Highway, Arlington, VA. Comments and data may also be submitted electronically by following the instructions under ``SUPPLEMENTARY INFORMATION.'' No confidential business information should be submitted through e-mail. 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). 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 p.m., Monday through Friday, excluding legal holidays. FOR FURTHER INFORMATION CONTACT: The product manager listed in the table below: ------------------------------------------------------------------------ Office location/ Product Manager telephone number Address ------------------------------------------------------------------------ Sidney Jackson (PM 5)......... Rm. 268, CM #2, 703- 1921 Jefferson 305-7610, e- Davis Hwy, mail:jackson.sidney@e Arlington, VA pamail.epa.gov. Bipin Gandhi (PM 5)........... Rm. 4W53, CS #2, 703- Do. 308-8380, e-mail: gandhi.bipin@epamail. epa.gov. ------------------------------------------------------------------------ SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as follows proposing the establishment and/or amendment of regulations for residues of certain pesticide chemicals in or on various food commodities under section 408 of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these petitions contain 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 support granting of the petition. Additional data may be needed before EPA rules on the petition. The official record for this notice of filing, as well as the public version, has been established for this notice of filing under docket control number [PF-801] (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 p.m., Monday through Friday, excluding legal holidays. The official record is located at the address in ``ADDRESSES'' at the beginning of this document. 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. Comment 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 FRL-5781-9 and appropriate petition number. Electronic comments on notice may be filed online at many Federal Depository Libraries. List of Subjects Environmental protection, Agricultural commodities, Food additives, Feed additives, Pesticides and pests, Reporting and recordkeeping requirements. Dated: April 1, 1998 James Jones, Director, Registration Division, Office of Pesticide Programs. Summaries of Petitions Petitioner summaries of the pesticide petitions are printed below as required by section 408(d)(3) of the FFDCA. The summaries of the petitions were prepared by the petitioners and represent the views of the petitioners. EPA is publishing the petition summaries verbatim without editing them in any way. The petition summary announces the availability of a description of the analytical methods available to EPA for the detection and measurement of the pesticide chemical residues or an explanation of why no such method is needed. 1. Interregional Research Project PP 2E4101 EPA has received a pesticide petition (PP 2E4101) from the Interregional Research Project Number 4 (IR-4), proposing pursuant to section 408(d) of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance for residues of the insecticide cyfluthrin, [cyano[4-fluoro-3- phenoxyphenyl]-methyl-3-[2,2- dicloroethenyl]-2,2- dimethylcyclopropanecarboxylate] in or on the raw agricultural commodity dried hops at 20.0 parts per million (ppm) and to remove the established tolerance for fresh hops at 4.0 ppm. EPA has determined that the petition contains data or information regarding the elements set forth in section 408(d)(2) of the Federal Food Drug and Cosmetic Act (FFDCA); however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the proposed tolerance. Additional data may be needed before EPA rules on the petition. This notice includes a summary of the petition prepared by Bayer Corporations (Bayer), the registrant. A. Residue Chemistry 1. Plant metabolism. The metabolism of cyfluthrin in plants is adequately understood. Studies have been conducted to delineate the metabolism of radiolabeled cyfluthrin in various crops all showing similar results. The residue of concern is cyfluthrin. [[Page 18412]] 2. Analytical method. Adequate analytical methodology (gas liquid chromatography with an electron capture detector) is available for enforcement purposes. The methodology was successfully validated by EPA's Beltsville laboratory in support of tolerances on cottonseed. The enforcement methodology has been submitted to the Food and Drug Administration for publication in the Pesticide Analytical Manual Vol. II (PAM II). Because of the long lead time for publication of the method in PAM II, the analytical methodology is being made available in the interim to anyone interested in pesticide enforcement when requested from Calvin Furlow, Public Response and Program Resource Branch, Field Operations Division (7502C), Office of Pesticide Programs, U.S. Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. Office location and telephone number: Rm. 119FF, CM #2, 1921 Jefferson-Davis Hwy., Arlington, VA 22202, (703) 305-5232. The established tolerances for residues of cyfluthrin in/on eggs, milks, fat, meat and meat by-products of cattle, goats, hogs, horses, sheep and poultry are adequate to cover secondary residues resulting from the proposed use as delineated in 40 CFR 180.6(a)(2). 3. Magnitude of residues. Import tolerances for cyfluthrin are presently established on fresh hops at 4.0 ppm and on dried hops at 20.0 ppm. IR-4 has conducted field trials in Washington, Oregon and Idaho in order to support expansion of the tolerances to include the domestic production of hops in the United States. The residue data submitted to the EPA by IR-4 consist of three trials, one each in Washington, Oregon and Idaho. In each trial, hops were planted in three plots, two treated and one untreated. Cyfluthrin (Baythroid 2) was applied by foliar (ground) application at a rate of 0.05 pounds(lb) active ingredient(ai)/acre(A) to one plot and 0.1 lb ai/A to another. Five separate applications were made with an interval of 7-days between the last application and harvest. Residues of cyfluthrin were detected in all treated samples from each trial and no interferences were detected in samples from control plots. The residue data are consistent for each trial. Cyfluthrin applied at 0.05 lb ai/A was detected from 0.44 to 0.78 ppm on fresh hops and from 1.83 to 2.36 ppm on dried hops. At 0.10 lb ai/A, residues were detected at 1.10 to 2.70 ppm on fresh hops and 3.76 to 7.57 ppm on dried hops. B. Toxicological Profile The data base for cyfluthrin is essentially complete. Data lacking but desirable are an acute neurotoxicity study in rats and a 90-day neurotoxicity study in rats. Although these data are lacking, Bayer believes the available toxicity data are sufficient to support the proposed tolerance and these missing data will not significantly change its risk assessment. Bayer has committed to submit the acute neurotoxicity study and the 90-day neurotoxicity study. 1. Acute toxicity. Results of acute toxicity tests show an acute oral lethal dose (LD<INF>50</INF>) grater than or equal to 16.2 milligram (mg)/ kilogram (kg), a dermal (LD<INF>50</INF>) >5,000 mg/kg, inhalation lethal concentration (LC<INF>50</INF> greater than or equal to 0.468 mg/liter(L), primary eye irritation and primary dermal irritation show toxicity categories III and IV, respectively. Dermal sensitization tests conducted show that cyfluthrin is not a dermal sensitizer. 2. Genotoxicty. Mutagenicity tests were conducted, including several gene mutation assays (reverse mutation and recombination assays in bacteria and a Chinese hamster ovary(CHO)/HGPRT assay); a structural chromosome aberration assay (CHO/sister chromatid exchange assay); and an unscheduled DNA synthesis assay in rat hepatocytes. All tests were negative for genotoxicity. 3. Reproductive and developmental toxicity. An oral developmental toxicity study in rats with a maternal and fetal no-observed effect level (NOEL) of 10 mg/kg/day (highest dose tested). An oral developmental toxicity study in rabbits with a maternal NOEL of 20 mg/ kg/day and a maternal lowest effect level (LEL) of 60 mg/kg/day, based on decreased body weight gain and decreased food consumption during the dosing period. A fetal NOEL of 20 mg/kg/day and a fetal LEL of 60 mg/ kg/day were also observed in this study. The LEL was based on increased resorptions and increased postimplantation loss. A developmental toxicity study in rats by the inhalation route of administration with a maternal NOEL of 0.0011 mg/l and a LEL of 0.0047 mg/l, based on reduced mobility, dyspnea, piloerection, ungroomed coats and eye irritation. The fetal NOEL is 0.00059 mg/l and the fetal LEL is 0.0011 mg/l, based on sternal anomalies and increased incidence of runts. A second developmental toxicity study in rats by the inhalation route of administration has been submitted to the Agency. A 3- generation reproduction study in rats with a systemic NOEL of 2.5 mg/ kg/day and a systemic LEL of 7.5 mg/kg/day due to decreased parent and pup body weights. The reproductive NOEL and LEL are 7.5 mg/kg/day and 22.5 mg/kg/day respectively. 4. Subchronic toxicity. In a 28-day oral toxicity study in rats, cyfluthrin demonstrated a NOEL of 20 mg/kg/day. The lowest-observed- effect level (LOEL) was 80 (40) mg/kg/day in both sexes based on clinical signs of nerve toxicity, decreases in body weight gain, and changes in liver and adrenal weights. The high dose was 80 mg/kg/day during the first and third weeks and 40 mg/kg/day during the second and fourth weeks. In a six month dog feeding study established a NOEL at 5 mg/kg/day for male and females. The LOEL for this study was 15 mg/kg/day for both sexes, based on neurological effects (hindlimb abnormalities) and gastrointestinal disturbances. A 21-day repeated dose dermal toxicity study, male and female rats were treated with cyfluthrin by dermal occlusion at target doses of 0, 100, 340, or 1,000 mg/kg/day for 6 hours/day (average actual dose levels were 0, 113, 376 or 1,077 mg/kg/day). No mortality was observed, and there were no treatment-related effects on body weight, ophthalmology, organ weights, clinical biochemistry, or hematology. The LOEL for dermal effects was 376 mg/kg/day for male and female Sprague- Dawley rats based on gross and histological skin lesions. The NOEL for dermal effects was 113 mg/kg/day. The LOEL for systemic effects was 1,077 mg/kg/day based on decreased food consumption, red nasal discharge and urine staining. The NOEL for systemic effects was 376 mg/ kg/day. 5. Chronic toxicity. A 12-month chronic feeding study in dogs with a NOEL of 4 mg/kg/day. The LEL for this study is established at 16 mg/ kg/day, based on slight ataxia, increased vomiting, diarrhea and decreased body weight. A 24-month chronic feeding/carcinogenicity study in rats showed a NOEL of 2.5 mg/kg/day and LEL of 6.2 mg/kg/day, based on decreased body weights in males, decreased food consumption in males, and inflammatory foci in the kidneys in females. 6. Carcinogenicity. A 24-month carcinogenicity study in mice was conducted. There were no carcinogenic effects observed under the conditions of the study. A 24-month chronic feeding/carcinogenicity study in rats was conducted. There were no carcinogenic effects observed under the conditions of the study. [[Page 18413]] Cyfluthrin has been classified as a Group E chemical (evidence of non-carcinogenicity for humans) by the Agency. The classification was based on a lack of convincing evidence of carcinogenicity in adequate studies with two animal species, rat and mouse. 7. Animal metabolism. A metabolism study in rats showed that cyfluthrin is rapidly absorbed and excreted, mostly as conjugated metabolites in the urine, within 48 hours. An enterohepatic circulation was observed. 8. Ednocrine effects. No special studies investigating potential estrogenic or endocrine effects of cyfluthrin 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. According to Bayer no endocrine effects were noted in any of the studies. C. Aggregate Exposure 1. Dietary exposure. In examining aggregate exposure, FFDCA section 408 requires that EPA take into account available and reliable information concerning exposure from the pesticide residue in the food in question, residues in other foods for which there are tolerances, residues in ground water or surface water that is consumed as drinking water, and other non-occupational exposures through pesticide use in gardens, lawns, or buildings (residential and other indoor uses). Dietary exposure to residues of a pesticide in a food commodity are estimated by multiplying the average daily consumption of the food forms of that commodity by the tolerance level or the anticipated pesticide residue level. The Theoretical Maximum Residue Contribution (TMRC) is an estimate of the level of residues consumed daily if each food item contained pesticide residues equal to the tolerance. In evaluating food exposures, EPA takes into account varying consumption patterns of major identifiable subgroups of consumers, including infants and children. The TMRC is a ``worst case'' estimate since it is based on the assumptions that food contains pesticide residues at the tolerance level and that 100% of the crop is treated by pesticides that have established tolerances. If the TMRC exceeds the Reference Dose (RfD) or poses a lifetime cancer risk that is greater than approximately one in a million, EPA attempts to derive a more accurate exposure estimate for the pesticide by evaluating additional types of information (anticipated residue data and/or percent of crop treated data) which show, generally, that pesticide residues in most foods when they are eaten are well below established tolerances. 2. Food. Under a petition to establish tolerances for cyfluthrin in or on citrus (PP 4F4313 and FAP 4H5687, the EPA has recently performed a chronic dietary exposure/risk assessment for cyfluthrin using a RfD of 0.025 mg/kg body weight(bwt)/day, based on a NOEL of 50 ppm (2.5 mg/ kg bwt/day) and an uncertainty factor of 100. The NOEL was determined in a 2-year rat feeding study. The endpoint effects of concern were decreased body weights in males and inflammation of the kidneys in females at the LEL of 6.2 mg/kg/day. This dietary exposure/risk assessment estimated the current dietary exposure for the U.S. population resulting from established tolerances, including the current 4 ppm tolerance on fresh hops, is 0.002907 mg/kg/bwt day. This represents 11.6% of the RfD. The exposure to children (1-6 years old), the subgroup population exposed to the highest risk was 0.00662 mg/kg/ bwt/day or 26.4% of the RfD. The current action will increase the exposure to 0.003266 mg/kg/bwt day or 13% of the RfD for the U.S. population and 0.006622 mg/kg/bwt day or 26.4% or the RfD for children (1-6 years old). Generally speaking, EPA has no cause for concern if the total dietary exposure from residues for uses for which there are published and proposed tolerances is less than the RfD. Therefore, Bayer concludes that the chronic dietary risk of cyfluthrin, as estimated by the dietary risk assessment, does not appear to be of concern. 3. Drinking water. Cyfluthrin is immobile in soil, therefore, will not leach into ground water. Additionally, due to the insolubility and lipophilic nature of cyfluthrin, any residues in surface water will rapidly and tightly bind to soil particles and remain with sediment, therefore, Bayer does not anticipate dietary exposures to cyfluthrin from drinking water. 4. Non-dietary exposure. Non-occupational exposure to cyfluthrin may occur as a result of inhalation or contact from indoor residential, indoor commercial, and outdoor residential uses. Reliable data to determine aggregate exposures from these sources are currently not available. However, determinations of worst case exposure from inhalation in indoor settings (continuous exposure at saturation vapor concentration) indicated that adequate margins of safety existed even under these conditions. Since this evaluation greatly overestimated exposure, the contribution to aggregate exposure from inhalation in normal uses would be expected to be negligible. Estimations of outdoor residential exposure have been required for cyfluthrin in a data call- in issued in 1995. These data are being generated by the Outdoor Residential Exposure Task Force (ORETF). However, available data show that the acute dermal toxicity of cyfluthrin is very low, with the LD<INF>50</INF> being greater than 5,000 mg/kg, the highest dose tested. Sub-acute (21-day) dermal toxicity data showed only localized (skin) effects at higher level exposures (1,000 mg/kg/day and 340 mg/ kg/day). Other than skin effects at these high exposure levels, no effects were observed at any exposure levels, the highest level tested being 1,000 mg/kg/day. The use rate for cyfluthrin on residential turf is 1 g (1,000 mg) active ingredient per 1,000 square feet which would indicate that potential exposures would be well below levels tested. In addition, the localized skin effects seen at the prolonged higher exposures in animal tests have not been reported for non-occupational exposures to cyfluthrin in currently accepted uses, indicating that exposures are below the threshold of any observable effects. Indoor uses are limited to areas with little or no contact, so exposures would be expected to be even less. Thus, the dermal route of exposure does not appear to be significant and the contribution to aggregate exposure from dermal contact would be expected to be negligible. D. Cumulative Effects In consideration of potential cumulative effects of cyfluthrin and other substances that have a common mechanism of toxicity, Bayer concludes that there are currently no available data or other reliable information indicating that any toxic effects produced by cyfluthrin would be cumulative with those of other chemical compounds; thus only the potential risks of cyfluthrin have been considered in this assessment of its aggregate exposure. E. Safety Determination 1. U.S. population. Using the conservative exposure assumptions described above and based on the completeness and reliability of the toxicity data it can be concluded that total aggregate exposure to cyfluthrin from all current uses as well as the proposed tolerance will utilize little more than 13% of the RfD for the U.S. population. EPA generally has no concerns for exposures below 100% of [[Page 18414]] the RfD, because the RfD represents the level at or below which daily aggregate exposure over a lifetime will not pose appreciable risks to human health. Thus, it can be concluded that there is a reasonable certainty that no harm will result from aggregate exposure to cyfluthrin residues. 2. Infants and children. In assessing the potential for additional sensitivity of infants and children to residues of cyfluthrin, the data from developmental studies in both rat and rabbit and a 2-generation reproduction study in the rat can be considered. The developmental toxicity studies evaluate any potential adverse effects on the developing animal resulting from pesticide exposure of the mother during prenatal development. The reproduction study evaluates any effects from exposure to the pesticide on the reproductive capability of mating animals through 2-generations, as well as any observed systemic toxicity. FFDCA section 408 provides that EPA may apply an additional safety factor for infants and children in the case of threshold effects to account for pre- and post- natal effects and the completeness of the toxicity database. Based on current toxicological data requirements, the toxicology database for cyfluthrin relative to pre- and post-natal effects is complete. The NOELs observed in the developmental and reproduction study are equivalent or higher than the NOEL from the 2- year rat feeding study, used with a 100 fold uncertainty factor to establish the reference dose. Therefore, Bayer believes that an additional uncertainty factor is not warranted and that the RfD at 0.025 mg/kg/day is appropriate for assessing aggregate risk to infants and children. Using the conservative exposure assumptions described above, cyfluthrin residues resulting from established tolerances, including a tolerance of 20 ppm on dry hops, would utilize 26.4% of the RfD for children (1-6 years old), the subgroup population exposed to the highest risk. Generally, EPA has no cause for concern if the exposure is less than 100% of the RfD. Therefore, based on the completeness and the reliability of the toxicity data and the conservative exposure assessment, Bayer concludes that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the residues of cyfluthrin, including all anticipated dietary exposure and all other non-occupational exposures. F. International Tolerances A Codex maximum residue levels (MRLs) or 20 ppm has been established for residues of cyfluthrin on dried hops. [FR Doc. 98-9395 Filed 4-14-98; 8:45 am] BILLING CODE 6560-50-F