Notice of Filing of Pesticide Petitions

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-836] (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. 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 (insert docket number) 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: October 27, 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. Bayer Corporation

PP 8F5023

EPA has received a pesticide petition (PP 8F5023) 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 a tolerance for residues of cyfluthrin: [cyano[4-fluoro-3-phenoxyphenyl]-methyl-3- [2,2-dichloroethenyl]-2,2-dimethyl-cyclopropanecarboxylate] in or on the raw agricultural commodity soybean, bean at 0.03 parts per million (ppm); soybean, forage at 8.0 ppm; soybean, hay at 4.0 ppm; field corn, forage at 3.0 ppm; and field corn, fodder at 6.0 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. 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. 2. Analytical method. Adequate analytical methodology (gas/liquid chromatography with an electron capture detector) is available for enforcement purposes. 3. Magnitude of residues. Cyfluthrin is the active ingredient in the registered end-use product Baythroid 2 Emulsifiable Pyrethroid Insecticide, EPA Reg. No. 3125-351. Data to support the proposed tolerances have been submitted to the Agency.

B. Toxicological Profile

1. Acute toxicity. There is a battery of acute toxicity studies for cyfluthrin supporting an overall toxicity Category II for the active ingredient. 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 adverse effect level (NOAEL) of 10 milligram/kilogram body weight/day (mg/kg/ bwt/day) highest dose tested (HDT). An oral developmental toxicity study in rabbits with a maternal NOAEL of 20 mg/kg/bwt/day and a maternal lowest effect level (LEL) of 60 mg/kg/bwt/day, based on decreased body weight gain and decreased food consumption during the dosing period. A fetal NOAEL of 20 mg/kg/ bwt/day and a fetal LEL of 60 mg/kg/ bwt/day were also observed in this study. The LEL was based on increased resorptions and increased postimplantation loss. A 3-generation reproduction study in rats with systemic toxicity NOAELs of 7.5 and 2.5 mg/kg/bwt/day for parental animals and their offspring, respectively. At higher dose levels (HDLs), the body weights of parental animals and their offspring were reduced. 4. Subchronic toxicity. A subchronic toxicity feeding study using rats demonstrated a NOAEL of 22.5 mg/kg/bwt/day, the HDT. A 6 month toxicity feeding study in dogs established a NOAEL of 5 mg/kg/ bwt/day. The LEL was 15 mg/kg/bwt/day based on clinical signs and reduced thymus weights. 5. Chronic toxicity. A 12 month chronic feeding study in dogs established a NOAEL of 4 mg/kg/bwt/day. The LEL for this study is established at 16 mg/kg/bwt/day, based on slight ataxia, increased vomiting, diarrhea and decreased body weight. A 24 month chronic feeding/carcinogenicity study in rats demonstrated a NOAEL of 2.5 mg/kg/bwt/day and LEL of 6.2 mg/kg/bwt/day, based on decreased body weights in males, decreased food consumption in males, and inflammatory foci in the kidneys in females. A 24 month carcinogenicity study in mice was conducted. Under the conditions of the study there were no carcinogenic effects observed. A 24 month chronic feeding/carcinogenicity study in rats was conducted. There were no carcinogenic effects observed under the conditions of the study. 6. 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. 7. Metabolite toxicology. No toxicology data have been required for cyfluthrin metabolites. The residue of concern is cyfluthrin. 8. Endocrine disruption. There is no evidence of endocrine effects in any of the studies conducted with cyfluthrin, thus, there is no indication at this time that cyfluthrin causes endocrine effects.

C. Aggregate Exposure

1. Dietary exposure-- Food. Dietary exposure was estimated using Novigen's Dietary Exposure Evaluation Model (DEEM) software; results from field trial and processing studies; consumption data from the USDA Continuing Surveys of Food Intake by Individuals (CSFIIs), conducted from 1989 through 1992; and information on the percentages of crops treated with cyfluthrin. Cyfluthrin is currently registered for use in alfalfa, carrots, citrus, cotton, peppers, radishes, sorghum, sunflower, sugarcane, sweet corn, and tomatoes. In addition, it has an import tolerance for hops. Various formulations are registered for use in food handling establishments and in combination with another active ingredient, for use in field corn, pop corn and sweet corn. For potential cyfluthrin use on soybeans and field corn the impact on the exposure assessment was examined. Chronic dietary exposure estimates with the current label uses for the overall U.S. population were 0.9% of the reference dose (RfD) (0.008 mg/kg/ bwt/day). When soybeans, field corn and potatoes were included the chronic dietary exposure estimates for the overall U.S. population were 0.8% of the RfD. For the most highly exposed population subgroups, non-nursing infants (50 in the rat is >5,000 milligrams/kilogram (mg/kg) in both males and females and the acute dermal LD50 in the rabbit is >2,000 mg/kg. The inhalation LC50 in the rat is >5.04 mg/l of air. Diclosulam produced no indications of dermal irritation in rabbits or sensitization in the guinea pig, and only very slight transient eye irritation in the rabbit following acute exposure. End use formulations of diclosulam have similar low acute toxicity profiles. 2. Genotoxicty. In a battery of short-term in vitro genotoxicity tests (Ames, CHO/HGPRT, chromosomal aberration) and an in vivo cytogenetic assay, diclosulam was negative. 3. Reproductive and developmental toxicity. Diclosulam exhibited no effects on reproduction or fetal development. No effects on reproduction or fetal development in a multigeneration reproduction study in rats and no effects on reproductive performance or neonatal survival were seen at the highest dose tested (HDT) (limit test at 1,000 milligrams/kilogram/day (mg/kg/day). In a developmental toxicity study in rabbits, the maternal no observed adverse effect level (NOAEL) was 65 mg/kg/day and the developmental NOAEL was at least 650 mg/kg/ day. 4. Subchronic toxicity. Thirteen-week dietary toxicity studies in rats, mice and dogs were conducted. The primary target organs identified in these studies were the kidneys (rat), and the liver (rat, mouse and dog). In the rat 13-week study the NOAELs were 50 mg/kg/day in the male and 100 mg/kg/day in the female, based on liver histopathologic evaluation in males and decreased body weights in females. In the mouse, the NOAEL was 100 mg/kg/day based upon hepatocellular hypertrophy. An NOAEL of 5 mg/kg/day was established in the dog based upon centrilobular hepatocellular hypertrophy at 25 mg/ kg/day. In a 21-day repeated dermal application study in rabbits, diclosulam when given at a dose of 1,000 mg/kg/day produced no signs of dermal irritation or systemic toxicity. 5. Chronic toxicity. In a 2-year combined chronic toxicity/ oncogenicity study in the rat, the NOAEL for chronic toxicity was 5 mg/ kg/day based upon kidney effects characterized as slight, subtle alteration in kidney tubular morphology, mostly within the corticomedullary junction which likely represented more a physiologic adaptation than a pathological change indicative of a toxic injury. There was no evidence of an oncogenic response. In a 2-year dietary feeding study in B6C3F1 mice conducted at 50, 100, 250 and 500 mg/kg/ day, 50 mg/kg/day was considered the NOAEL in males and the NOAEL in females based upon histologic changes in the kidney. The lesion noted in male mice was a reduced vacuolation of the kidney tubular epithelium at all dose levels. Decreased absolute and relative kidney weights were seen at 100 mg/kg/day and above. In female mice, focal dilation with hyperplasia of the lining epithelium of the renal cortical tubules was seen at 100 mg/kg/day and above. There was no evidence of an oncogenic response. In a 1-year chronic toxicity study in dogs, the NOAEL was considered 25 mg/kg/day, the HDT. Measurable toxicity was anticipated based on the results of the 13-week study in dogs; however, the only treatment related effects were slight elevations in serum alkaline phosphatase and creatinine levels at 25 mg/kg/day, which were considered within the normal limits of variability in dogs. 6. Animal metabolism. Metabolism studies conducted on diclosulam indicated over 80% of a single or repeated dose of 5 mg/kg was absorbed, while at 500 mg/kg/day, there was incomplete absorption of diclosulam, with only 15-20% of the dose absorbed. Urinary elimination was rapid with half-lives of approximately 7-12 hours. Sex dependent differences in disposition of the 5 mg/kg dose were traced to more efficient elimination of unchanged diclosulam in the female versus male kidney but are of no known toxicologic significance. Due to its rapid elimination, diclosulam has little potential to accumulate upon repeated administration.

7. Metabolite toxicology. The residue of concern for tolerance setting purposes is the parent material (diclosulam). Thus, there is no need to address metabolite toxicity.

C. Aggregate Exposure

1. Dietary exposure--Food. For Purposes of assessing the potential dietary exposure from use of diclosulam on soybeans and peanuts, a conservative estimate of aggregate exposure is determined by Theoretical Maximum Residue Contribution (TMRC) assuming that 100% of the soybeans and peanuts have a residue of diclosulam at the proposed tolerance level of 0.02 ppm. This results in an extremely conservative estimate of exposure for diclosulam, because no residues are expected in these commodities at the proposed maximum label rate. The potential dietary exposure is obtained by multiplying the tolerance residue level on soybeans and peanuts (0.02 ppm) by the consumption data which estimates the amount of soybean and peanut products consumed by various population subgroups. The maximum potential average daily dose (ADD) of diclosulam values determined for various populations are clearly significant overestimates compared with actual exposure. When ADDs are compared to the Reference Dose (RfD), which uses the lowest NOAEL of 5 mg/kg/day from the 2-year rat chronic toxicity study and an uncertainty factor of 100, the ADD for all U.S. consumers including the highest exposed group, non-nursing infants under 1-year old, would theoretically be exposed to about 0.1% of the RfD. 2. Drinking water. Another potential source of dietary exposure are residues in drinking water. Based upon the available field dissipation and field run off studies conducted with diclosulam there is little potential for exposure to diclosulam in drinking water to cause any human health concern.

D. Cumulative Effects

There is no reliable information to indicate that diclosulam has a common mechanism of toxicity with any other chemical compound or that potential toxic effects of diclosulam would be cumulative with those of any other pesticide chemical. Thus Dow AgroSciences believes it is appropriate to consider only the potential risks of diclosulam in its exposure assessment.

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, Dow AgroSciences has concluded that aggregate exposure to diclosulam potentially can utilize about 0.1% of the RfD for non- nursing infants under 1-year old, theoretically the most exposed population. EPA generally has no concern for exposures below 100% of the RfD because the RfD represents the level at or below which daily aggregate dietary exposure over a lifetime will not pose appreciable risks to human health. Therefore, Dow AgroSciences concludes that there is a reasonable certainty that no harm will result from aggregate exposure to diclosulam residues in on soybeans and peanuts and its processed products. The complete toxicology profile for diclosulam shows no evidence of physiological effects characteristic of the disruption of the hormone estrogen. Based upon this observation, diclosulam does not meet the criteria for an estrogenic compound. 2. Infants and children. In assessing the potential for additional sensitivity of infants and children to residues of diclosulam, data from developmental toxicity studies in rats and rabbits and a multigeneration reproduction study in the rat are considered. The developmental toxicity studies are designed to evaluate adverse effects on the developing organism resulting from pesticide exposure during prenatal development to one or both parents. Reproduction studies provide information relating to effects from exposure to the pesticide on the reproductive capability and potential systemic toxicity of mating animals and on various parameters associated with the well-being of offspring. 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 toxicity and the completeness of the data base. Based on the current toxicological data requirements, the data base for diclosulam relative to pre- and post-natal effects for children is complete. Further, for diclosulam, the NOAEL in the chronic feeding study which was used to calculate the RfD (5 mg/kg/day) is already lower than the NOAELs from the developmental studies in rats and rabbits by a factor of more than 200-fold. Concerning the reproduction study in rats, there were no effects on reproduction or fetal development, even at a dose over 100 times the NOAEL used to establish the RfD. Therefore, Dow AgroSciences concludes that an additional uncertainty factor is not needed and that the RfD at 0.05 mg/kg/day is appropriate for assessing risk to infants and children. Using the conservative exposure assumptions previously described, the percent RfD utilized by the aggregate (diet, and drinking water) exposure to residues of diclosulam on soybeans and peanuts is 0.000051 mg/kg/day for non-nursing infants under 1-year old, theoretically the most exposed population subgroup. Thus, based on the completeness and reliability of the toxicity data and the conservative exposure assessment, Dow AgroSciences concludes that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to diclosulam on soybeans and peanuts.

F. International Tolerances

There are no Codex maximum residue levels established for residues of diclosulam on soybeans, peanuts or any other food or feed crop. [FR Doc. 98-31066 Filed 11-19-98; 8:45 am] BILLING CODE 6560-50-F