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Tolylfluanid (Bayer). August 11, 1997. Petition to Establish Import Tolerances for residues of the fungicide in or on apples and grapes at 5.0 ppm, hops at 30 ppm and tomatoes at 1.0 ppm. Federal Register.
[Federal Register: August 11, 1997 (Volume 62, Number 154)] [Notices] [Page 42980-42986] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr11au97-65] ----------------------------------------------------------------------- ENVIRONMENTAL PROTECTION AGENCY [PF-755; FRL-5736-1] 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-755, must be received on or before September 10, 1997. ADDRESSES: By mail submit written comments to: Public Information and Records Integrity Branch (7506C), Information Resources and Services Division, Office of Pesticides 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. 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 ------------------------------------------------------------------------ George LaRocca (PM 13)........ Rm. 204, CM #2, 703- 1921 Jefferson 305-6100, e-mail: Davis Hwy, larocca.george@epamai Arlington, VA l.epa.gov. Mary Waller, Acting (PM 21)... Rm. 265, CM #2, 703- Do. 308-9354, e-mail: firstname.lastname@example.org pa.gov. [[Page 42981]] James Tompkins, Acting (PM 25) Rm. 239, CM #2, 703- Do. 305-5697, e-mail: tompkins.jim@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 supports 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-755] (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: email@example.com 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 [PF-755] and appropriate petition number. Electronic comments on this 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: August 1, 1997. Peter Caulkins, Acting 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. Bayer Corporation PP 7E4825 EPA has received a pesticide petition (PP 7E4825) from Bayer Corporation, 8400 Hawthorn Road, Kansas City, MO 64120, 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 import tolerances for residues of the fungicide Tolylfluanid in or on the raw agricultural commodities apples and grapes at 5.0 parts per million (ppm), hops at 30 ppm and tomatoes at 1.0 ppm. EPA has determined that the petition contains data or information regarding the elements set forth in section 408(d)(2) of the FFDCA; 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. A. Residue Chemistry 1. Plant metabolism. Plant metabolism studies were conducted using radiolabeled tolylfluanid applied to apples, grapes, and strawberries. Unchanged parent tolylfluanid was the major metabolite identified in these studies. 2. Analytical method. Bayer has developed an analytical method for the determination of tolylfluanid residues in raw agricultural and processed commodities of apples, grapes, tomatoes, and hops. Samples are analyzed by gas chromatography using thermionic nitrogen-phosphorus detector or flame photometric detector following extraction, filtration, and cleanup procedures. The limit of quantitation is 0.02 mg/kg for all matrices, except it is 0.05 mg/kg for raisins and wet apple pomace, 0.5 mg/kg for green hop cones, and 1.0 mg/kg for dried hop cones. 3. Magnitude of residues. Bayer has conducted over 90 residue field trials in seven countries on apples, grapes, tomatoes, and hops. Residues of tolylfluanid in or on grapes harvested 14, 21 or 35 days following treatment according to recommended practices ranged from 0.03 mg/kg to 3.45 mg/kg, except residues of tolylfluanid were 5.08 mg/kg in one sample from a trial conducted in Spain. Residues of tolylfluanid ranged from 0.03 mg/kg to 0.66 mg/kg in tomatoes harvested 3 or 7 days following multiple applications with tolylfluanid. Residues of tolylfluanid ranged from 0.14 to 2.31 mg/kg in or on apples harvested 7 days after multiple applications with tolylfluanid. Residues of tolylfluanid in or on hops harvested 14 days following multiple applications ranged from 3.31 mg/kg to 27.0 mg/kg (dried cone) and ranged from 3.8 mg/kg to 17.6 mg/kg (green cone). Studies have also been conducted to evaluate the potential for concentration of tolylfluanid residues during the processing of apples, grapes, and tomatoes. Tolylfluanid does not have the potential to concentrate in the EPA required processed commodities consumed by humans for apples, grapes and tomatoes. Residues of tolylfluanid may have the potential to concentrate in wet apple pomace, an animal feed item. B. Toxicological Profile 1. Acute toxicity. Tolylfluanid exhibits low acute oral, dermal, and inhalation toxicity (LD<INF>50s</INF> >5,000 mg/kg b.w.). An acute neurotoxicity study showed no specific evidence of neurotoxicity; non- specific signs of toxicity were observed in this study (in females only) at doses at and greater than 150 mg/kg b.w. Tolylfluanid is a severe dermal irritant, moderately irritating to the eye, and a skin sensitizer. Tolylfluanid showed no systemic toxicity following subacute dermal administration, but did cause dermal irritation. Effects seen in the acute as well as subacute inhalation [[Page 42982]] study indicate tolylfluanid is a strong respiratory irritant. 2. Genotoxicity. The genotoxic potential of tolylfluanid was assessed in several in vivo and in vitro studies. The weight-of-the- evidence indicates that tolylfluanid is not genotoxic. 3. Reproductive and developmental toxicity. Tolylfluanid showed no evidence of developmental toxicity based on two rat developmental toxicity studies. Tolylfluanid showed evidence of developmental effects in rabbits but only at a maternally toxic dose level. Two complete 2-generation reproductive toxicity studies in rats and one supplementary 2-generation reproductive toxicity rat study have been conducted on tolylfluanid. Reproductive toxicity (decreased body weight development in pups and decreased number of pups born, birth weight, litter size, and lactation index) was noted only in the presence of parental toxicity (decreased body weight gain, organ weight changes, and hyperostosis of the crania). 4. Subchronic toxicity. Subchronic toxicity studies have been done with tolylfluanid in rats and dogs. Decreased body weight gain, decreased liver enzymes, slightly increased relative liver weights, and thyroid toxicity were noted in a subchronic rat dietary study (no correlating histopathological findings). Decreased body weight gain, increased liver enzyme activity, slightly increased relative liver weights, and increased PAS staining in the liver occurred in a subchronic dietary dog study. A subchronic neurotoxicity study in rats showed no evidence of neurotoxicity. 5. Chronic toxicity. Chronic toxicity studies on tolylfluanid were done in the rat, mouse and dog. Tolylfluanid was tested in two rat chronic dietary studies. Increased growth of the incisors of the upper jaw and skeletal changes (hyperostosis in the skull and ribs) resulted from the high fluorine content of the compound. Hepatotoxicity and renal toxicity were seen in rats, mice, and dogs. Hepatotoxicity was evidenced by hepatocellular cytoplasmic changes, vacuolation, and focal fatty changes in rats, hepatocellular hypertrophy and single cell necrosis in mice, decreased liver enzymes in rats, and increased liver enzymes in mice and dogs. Renal toxicity (microscopic kidney lesions, increased relative kidney weights, effects on urinalysis parameters) was probably attributable to the effects of fluoride on renal tubules. A second chronic toxicity study in dogs is currently ongoing (results not yet available). 6. Oncogenicity. Tolylfluanid showed no evidence of direct oncogenic activity in rats or mice. In rats tolylfluanid altered thyroid hormone levels and an increased incidence of hyperplastic and neoplastic lesions of the thyroid (primarily adenomas) in rats was observed. The thyroid neoplasia is considered to be a secondary (thresholdable) effect to altered thyroidal iodine metabolism and does not suggest a direct oncogenic effect. No treatment-related neoplasms were seen in the mouse oncogenicity study. Based on the chronic toxicity data, Bayer believes the RfD for tolylfluanid is 0.08 mg/kg, based on the no observed adverse effect level (NOAEL) of 8 mg/kg b.w./day for parental and reproductive toxicity identified in the second 2-generation rat reproductive toxicity study (Pinckel and Ricke, 1995) and an uncertainty factor of 100. No unique concern for toxicity to infants and children was identified, therefore an additional safety factor is not warranted. (Note there is a seven-fold difference between the NOAEL and lowest effect level (LEL). Using the Guidelines for Carcinogenic Risk Assessment published in September 1986, we believe the Agency will classify tolylfluanid as a Group C carcinogen (possible human carcinogen) based on benign thyroid tumors seen in the chronic rat studies). Mechanistic studies with tolylfluanid have shown that these tumors are induced through a nonlinear threshold mechanism similar to that discussed in EPA's thyroid policy document. Therefore, tolylfluanid should be regulated using the margin of exposure approach. 7. Animal metabolism. Metabolism studies were conducted using hens and goats. No residues of parent tolylfluanid were detected in any tissues, organs, milk, or eggs. Tolylfluanid is metabolized and excreted rapidly and efficiently in mammals. C. Aggregate Exposure 1. Dietary exposure. Food and drinking water/non-dietary exposure. 2. Food. A chronic dietary exposure analysis was conducted for tolylfluanid. The reference dose (RfD) was 0.08 mg/kg/day based on a NOEL of 8 mg/kg/day and an uncertainty factor of 100. The no observed effect level (NOEL) was obtained from the rat reproduction study and the effect was decreased pup viability and decreased body weights. The RfD could change based on the NOEL from a repeat chronic dog toxicity study which is currently ongoing (doses tested: 5, 20, and 80 mg/kg/day). The final report for this study is expected to be completed in the second part of 1997. If necessary, revising the RfD will be addressed at that time. Tolylfluanid does not have the potential to concentrate in processed commodities consumed by humans. The proposed MRLs for the respective crops were used for the raw agricultural and processed commodities for grapes (5 mg/kg), tomatoes, (1 mg/kg), and hops (30 mg/ kg). The anticipated residue level for fresh apples and apple juice was calculated by adjusting the proposed MRL for apples (5 mg/kg) for the percentage of fresh apples (4.8%) and apple juice (59.7%) consumed in the U.S. that are imported. No adjustments were made for the anticipated residue levels for grapes, tomatoes and hops. The results of the chronic dietary exposure analysis for the overall U.S. population and the three most highly exposed population subgroups are summarized as follows.. The exposure estimate was compared against the RfD of 0.08 mg/kg. The theoretical maximum residue contribution (TMRC) as percentage of the RfD, was 9.53% for the U.S. population, 53.36% for non-nursing infants, 38.02% for nursing infants (0-1 yr old), and 26.16% for children (1-6 yrs old). The anticipated residue contribution (ARC) as percentage of the RfD was 5.97% for the U.S. population, 23.29% for non-nursing infants, 15.41% for nursing infants and 15.10% for children. As seen above, chronic dietary exposure to tolylfluanid is less than 24% of the RfD for even the most highly exposed subgroup. In addition, these exposure estimates greatly over estimate the anticipated risk for the following reasons: (1) a relatively small percentage of these crops will be treated with tolylfluanid; (2) a small percentage of the treated crops are imported to the U.S.; (3) a small percentage of the total U.S. consumption of these crops are imported products; and (4) the actual residues in the imported commodities will likely be below the proposed MRLs. 3. Drinking water. Tolylfluanid residue levels in tap water, non- tap water, and water in commercially prepared food were assumed to be zero because tolylfluanid is not registered for use in the United States and therefore, the only exposure is from the importation of tolylfluanid-treated commodities. 4. Non-dietary exposure. Tolylfluanid is not registered in the United States, therefore there is no non-occupational, structural or residential exposure. D. Cumulative Effects Tolylfluanid is a fungicide that is somewhat structurally similar to [[Page 42983]] Captan, and appears to share a common mechanism of fungicidal action with this product. However, tolylfluanid does not show a similar mammalian toxicity profile to Captan, which has been reported to produce mouse gastrointestinal tumors and male rat kidney tumors. No significant cumulative toxicity to mammals based on a common mechanism of action to that of Captan is anticipated for tolylfluanid. Tolylfluanid alters the thyroid hormone balance, but: (1) no data exist showing specifically how tolylfluanid causes thyroid changes; (2) tolylfluanid is not known to be structurally similar to other thyroid tumorigens; (3) no common mechanism has been established or proposed and (4) even if it is eventually determined that the mechanism for thyroid tumorigenesis may be similar to other classes of pesticides, this endpoint is seen with tolylfluanid only at very high exposure levels. If an RfD for tolylfluanid were based on dose levels at which thyroid hormone levels were altered, a very low impact on a cumulative risk cup would be anticipated because the potency of tolylfluanid is very low. Endocrine effects. Endocrine-related effects of tolylfluanid exposure appear to be limited to the thyroid. No evidence of estrogenic or anti-estrogenic activity was present in the available animal studies. The developmental toxicity and reproductive toxicity studies showed no effects suggesting endocrine disruption, (e.g., change in fetal sex ratios, change in estrous cycles or mating performance, change in fertility, or malformed or altered reproductive organ development). E. Safety Determination 1. U.S. population. A chronic dietary exposure analysis was conducted for tolylfluanid. The chronic dietary exposure to tolylfluanid is 5.97% of the RfD for the U.S. population, using the ARC. 2. Infants and children. A chronic dietary exposure analysis was conducted for tolylfluanid. The chronic dietary exposure to tolylfluanid is 23.29% of the RfD for non-nursing infants, the most highly exposed group, using the ARC. F. International Tolerances The current Codex tolerances for tolylfluanid are based on residues of parent only. The Codex tolerances are: 5 mg/kg for currents (black, red, and white), 2 mg/kg for Gherkins, 1 mg/kg for head lettuce, 5 mg/ kg for pome fruits, 3 mg/kg for strawberries, and 2 mg/kg for tomatoes. (Mary Waller)