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Fluazinam (ISK). December 6, 2000, Petition to Extend Pesticide Tolerances on potato and peanut at 0.02 ppm and wine grapes at 3.0 ppm. Federal Register.
Note: there were 2 pesticide petitions in this Notice. We only include the one for Fluazinam.
http://www.epa.gov/fedrgstr/EPA-PEST/2000/December/Day-06/p31056.htm
[Federal Register: December 6, 2000 (Volume 65, Number 235)] [Notices] [Page 76253-76258] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr06de00-68] ----------------------------------------------------------------------- ENVIRONMENTAL PROTECTION AGENCY [PF-983; FRL-6573-7] Notice of Filing Pesticide Petitions to Establish and to Extend Tolerances for Certain Pesticide Chemicals in or on Food 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 docket control number PF-983, must be received on or before January 5, 2001. ADDRESSES: Comments may be submitted by mail, electronically, or in person. Please follow the detailed instructions for each method as provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure proper receipt by EPA, it is imperative that you identify docket control number PF-983 in the subject line on the first page of your response. FOR FURTHER INFORMATION CONTACT: For Pesticide Petition (PP 9F5079) contact: Cynthia Giles-Parker, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington DC 20460; Telephone number: (703) 305-7740; e- mail address: giles-parker.cynthia@epa.gov. For Pesticide Petitions (PP 8F3654 8F3674) contact: Mary Waller, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington DC 20460; Telephone number: (703) 308-9354; e-mail address: waller.mary@epa.gov. SUPPLEMENTARY INFORMATION: I. General Information A. Does this Action Apply to Me? You may be affected by this action if you are an agricultural producer, food manufacturer or pesticide manufacturer. Potentially affected categories and entities may include, but are not limited to: ------------------------------------------------------------------------ Examples of Categories NAICS codes potentially affected entities ------------------------------------------------------------------------ Industry 111 Crop production 112 Animal production 311 Food manufacturing 32532 Pesticide manufacturing ------------------------------------------------------------------------ This listing is not intended to be exhaustive, but rather provides a guide for readers regarding entities likely to be affected by this action. Other types of entities not listed in the table could also be affected. The North American Industrial Classification System (NAICS) codes have been provided to assist you and others in determining whether or not this action might apply to certain entities. If you have questions regarding the applicability of this action to a particular entity, consult the person listed under FOR FURTHER INFORMATION CONTACT. B. How Can I Get Additional Information, Including Copies of this Document and Other Related Documents? 1. Electronically. You may obtain electronic copies of this document, and certain other related documents that might be available electronically, from the EPA Internet Home Page at http://www.epa.gov/. To access this document, on the Home Page select ``Laws and Regulations'' and then look up the entry for this document under the ``Federal Register--Environmental Documents.'' You can also go directly to the Federal Register listings at http://www.epa.gov/fedrgstr/. 2. In person. The Agency has established an official record for this action under docket control number PF-983. The official record consists of the documents specifically referenced in this action, any public comments received during an applicable comment period, and other information related to this action, including any information claimed as confidential business information (CBI). This official record includes the documents that are physically located in the docket, as well as the documents that are referenced in those documents. The public version of the official record does not include any information claimed as CBI. The public version of the official record, which includes printed, paper versions of any electronic comments submitted during an applicable comment period, is available for inspection in the Public Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall #2 (CM #2), 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The PIRIB telephone number is (703) 305-5805. C. How and to Whom Do I Submit Comments? You may submit comments through the mail, in person, or electronically. To ensure proper receipt by EPA, it is imperative that you identify docket control number PF-983 in the subject line on the first page of your response. 1. By mail. Submit your comments to: Public Information and Records Integrity Branch (PIRIB), Information Resources and Services Division (7502C), Office of Pesticide Programs (OPP), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460. 2. In person or by courier. Deliver your comments to: Public Information and Records Integrity Branch (PIRIB), Information Resources and Services Division (7502C), Office of Pesticide Programs (OPP), Environmental Protection Agency, Rm. 119, CM#2, 1921 Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The PIRIB telephone number is (703) 305-5805. 3. Electronically. You may submit your comments electronically by e-mail to: opp-docket@epa.gov, or you can submit a computer disk as described above. Do not submit any information electronically that you consider to be CBI. Avoid the use of special characters and any form of encryption. Electronic submissions will be accepted in Wordperfect 6.1/ 8.0 or ASCII file format. All comments in electronic form must be identified by docket control number PF-983. Electronic comments may also be filed online at many Federal Depository Libraries. D. How Should I Handle CBI That I Want to Submit to the Agency? Do not submit any information electronically that you consider to be CBI. You may claim information that you submit to EPA in response to this document as CBI by marking any part or all of that information as CBI. Information so marked will not be disclosed except in accordance with procedures set forth in 40 CFR part 2. [[Page 76254]] In addition to one complete version of the comment that includes any information claimed as CBI, a copy of the comment that does not contain the information claimed as CBI must be submitted for inclusion in the public version of the official record. Information not marked confidential will be included in the public version of the official record without prior notice. If you have any questions about CBI or the procedures for claiming CBI, please consult the person identified under FOR FURTHER INFORMATION CONTACT. E. What Should I Consider as I Prepare My Comments for EPA? You may find the following suggestions helpful for preparing your comments: 1. Explain your views as clearly as possible 2. Describe any assumptions that you used. 3. Provide copies of any technical information and/or data you used that support your views. 4. If you estimate potential burden or costs, explain how you arrived at the estimate that you provide. 5. Provide specific examples to illustrate your concerns. 6. Make sure to submit your comments by the deadline in this notice. 7. To ensure proper receipt by EPA, be sure to identify the docket control number assigned to this action in the subject line on the first page of your response. You may also provide the name, date, and Federal Register citation. II. What Action is the Agency Taking? 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. List of Subjects Environmental protection, Agricultural commodities, Feed additives, Food additives, Pesticides and pests, Reporting and recordkeeping requirements. Dated: November 21, 2000. James Jones, Director, Registration Division, Office of Pesticide Programs. Summaries of Petitions Petitioner summaries of the pesticide petitions are printed below as required bysection 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. ISK Biosciences Corporation (PP 9F5079) Summary of Petition EPA has received a pesticide petition (PP 9F5079) from ISK Biosciences Corporation, 5970 Heisley Road, Suite 200, Mentor, Ohio, 44060, proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance for residues of fluazinam in or on the raw agricultural commodities potato and peanut at 0.02 parts per million (ppm) and wine grapes at 3.0 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 residue of concern is best defined as the parent, fluazinam. The metabolism of fluazinam in plants (potatoes, peanuts, and wine grapes) is adequately understood for the purposes of these tolerances. The metabolism of fluazinam involves initial reduction of the nitro groups, hydrolysis of the trifluoromethyl group as well as replacement of chlorine by glutathione with subsequent reactions along the glutathione pathway. Parent fluazinam is rapidly degraded and is either not found or barely detectable in peanuts and potatoes. Fluazinam parent was the major identifiable residue in a grape metabolism study. Identifiable residues in plant metabolism studies either closely resemble fluazinam in structure or are the result of re-incorporation of the fluazinam carbon pool into natural products. Ruminant and poultry metabolism studies demonstrated that the transmittal of residues from the feed of goats and hens through to meat, milk, and eggs was low. Total 14C residues were below 1 ppm in all tissues, milk and eggs. Identifiable residues were less than 2% of the administered dose in all matrices, except for chicken fat and liver. 2. Analytical method. An analytical method using gas chromatography with electron capture detection (GC-ECD) for the determination of fluazinam residues on potatoes, peanuts, grapes and the processing fractions thereof has been developed and validated. The method involves solvent extraction followed by liquid-liquid partitioning and concentration prior to a final purification using column chromatography. The method has been successfully validated by an independent laboratory using peanut nutmeat as the matrix. The limit of quantitation of the method is 0.02 ppm in peanuts and 0.01 ppm in potatoes and grapes. 3. Magnitude of residues--i. Potatoes. Data from 11 field trials in potatoes showed that mean fluazinam residues from duplicate samples were 0.01 ppm in the RAC commodity at all locations. The result of a processing study using a 3.5X application rate showed no concentration into the processing fractions dry peels, french fries and chips. A calculated processing factor of 2.4 for the animal feed commodity wet peels was determined based on residue levels just slightly above the limit of quantitation. ii. Peanuts. A total of 15 field trials were conducted over three growing seasons at nine sites representative of peanut production. Residues of fluazinam in nutmeat from all location were below 0.01 ppm. Residues in peanut hay, a grazing restriction commodity, ranged from 0.16 to 10.2 ppm in the six locations where it was harvested. In a processing study, residues concentrated 3x in crude oil and 5x in soapstock, but did not concentrate in refined oil or presscake. iii. Wine grapes. A total of 20 field trials were conducted over three growing seasons in major wine grape growing regions worldwide. Residues of fluazinam in grapes ranged from 0.03 to 2.27 ppm. Vinification of grapes from two locations showed a reduction of fluazinam in wine to non-detectable levels. iv. Secondary residues. Since levels of fluazinam in potatoes and peanut nutmeat were below detectable levels [[Page 76255]] (the fluazinam label includes a peanut hay grazing restriction, and only wine grapes which are imported are included in this tolerance petition), no residues of concern are expected on animal feed items. Furthermore, since animal metabolism studies do not show potential for significant residue transfer, detectable secondary residues in animal tissues, milk or eggs are not expected. Therefore, tolerances are not needed for these commodities. B. Toxicological Profile 1. Acute toxicity. A battery of acute toxicity studies was conducted which placed technical fluazinam in Toxicity Category III for oral LD50, dermal LD50, dermal irritation, Category II for inhalation LC50 and Category I for eye irritation. Technical fluazinam showed potential for dermal sensitization. In an acute neurotoxicity study, the no observed affect effect level (NOAEL) for neurotoxicity was 2,000 milligram/kilogram (mg/kg) highest dose tested (HDT) and the NOAEL for systemic effects was 50 mg/ kg. 2. Genotoxicty. A battery of tests has been conducted to assess the genotoxic potential of technical fluazinam. Assays conducted included two gene mutation tests in bacteria, a chromosomal aberration test in mammalian cells, a mouse micronucleus test and a DNA repair test in bacteria. Technical fluazinam did not elicit a genotoxic response in any of the studies conducted. 3. Reproductive and developmental toxicity. In a 2-generation reproductive toxicity study, the NOAEL for reproductive effects was 100 ppm (10.1 mg/kg/day). The NOAEL for parental toxicity was 20 ppm (2.1 mg/kg/day). In a rat developmental study, there were no developmental effects observed at non-maternally toxic doses. The developmental NOAEL was 50 mg/kg/day and the lowest observed adverse effect level (LOAEL) was 250 mg/kg/day, based upon statistically significant decreased mean fetal body weight and other evidence suggestive of delayed fetal development related to maternal toxicity. The maternal NOAEL was shown to be 50 mg/ kg/day. In a rabbit developmental study, there were no developmental effects observed at non-maternally toxic doses. The developmental NOAEL was 7 mg/kg/day and the LOAEL was 12 mg/kg/day, based on increased incidence of total litter loss and possible slightly increased incidences of fetal findings at this dose. It was concluded that the maternal NOAEL was 4 mg/kg/day. 4. Subchronic toxicity. The NOAEL for the 13 week feeding study in rats was 50 ppm (4.1 mg/kg/day). The LOAEL was 500 ppm (41 mg/kg/day), based on periacinar hepatocellular hypertrophy and sinusoidal chronic inflammation in males, increased liver weights in males and increased lung weights in females. In a 13 week dog study, the NOAEL was 10 mg/kg/day. The LOAEL was 100 mg/kg/day, based on ocular change observed ophthalmoscopically and liver effects consisting of increased relative liver to body weight, bile duct hyperplasia with or without cholangiofibrosis and increased plasma phosphatase levels. In a 21 day dermal study, the NOAEL for systemic effects was 10 mg/ kg/day. The LOAEL was 100 mg/kg/day, based on hepatocelluar hypertrophy and increases in AST and cholesterol levels. In a subchronic neurotoxicity study, no effects considered to be indicative of neurotoxicity were observed at the highest dose tested, 3,000 ppm (233 mg/kg/day). The NOAEL for systemic toxicity (body weight differences) was 1,000 ppm (74 mg/kg/day). 5. Chronic toxicity. Fluazinam was not carcinogenic in rats. A NOAEL of 10 ppm (0.43 mg/kg/day) of fluazinam was established based on the following effects at 1,000 and/or 100 ppm: lower food consumption and efficiency of food utilization, slight anemia, elevated cholesterol, increased liver weights, an increased number of macroscopic liver and testes lesions and an increased incidence of microscopically observed lung, liver, pancreas, lymph node and testes lesions. An additional study was conducted to further define the NOAEL for long-term effects in the rat. In the second study, a NOAEL of 50 ppm (2.2 mg/kg/day) was established based on liver and testes effects. Two long-term feeding studies were conducted in mice. In the first, the NOAEL for all effects was 10 ppm (1.14 mg/kg/day) and the LOAEL was 100 ppm (11.2 mg/kg/day) based on the treatment-related effects observed in the liver. A second oncogenicity study in mice was conducted at 1,000, 3,000 and 7,000 ppm to ensure that an maximum tolerance dose (MTD) was studied. Findings included increased female mortality, reduced body weight gains, increased brain weights and/or liver weights. An impurity in the test material used in this study resulted in vacuolation of the white matter of the brain and cervical spinal cord in treated animals. A statistically significant higher incidence of hepatocellular adenomas was observed in the 3,000 ppm dose males. Hepatocellular adenomas are common tumors in male mice. There was no dose relationship in the induction of the adenoma and no increase in hepatocellular carcinomas. It was concluded that fluazinam is not carcinogenic in the mouse. In a chronic dog study, the NOAEL was determined to be 1 mg/kg/day. The LOAEL was 10 mg/kg/day based on generalized, nonspecific toxicity. No ocular effects were observed ophthalmoscopally at any dose in this study. 6. Animal metabolism. After an oral dose of fluazinam the median peak time for blood concentration of radiolabel activity for both sexes was 6 hours. The major route of excretion was the feces with urine contributing as a minor route. Less than 1% of the administered dose was found in the terminated animals. The highest concentration was found in the liver. There were no major differences related to sex or dose level in the findings. It was concluded that fluazinam is metabolized by both reduction and glutathione and glucuronide conjugation and further metabolism. 7. Metabolite toxicology. The same metabolic processes occur in plants and animals but metabolism in plants is more extensive than in animals. All of the major identified metabolites in both plants and animals retain the phenylpyridinylamine structure. Many of the metabolites resulting from fluazinam are similar in plants and animals and, therefore, have already been evaluated toxicologically. Because of the rapid and complete elimination (in animals) and re- incorporation (in plants) of fluazinam, the toxicity of metabolites is expected to be similar to but lower than the toxicity of the parent compound. The residue of concern is parent fluazinam only. 8. Endocrine disruption. The toxicological profile of fluazinam shows no evidence of physiological effects characteristic of the disruption of the hormone estrogen in mammalian chronic studies or in mammalian or avian reproduction studies. It is therefore considered that there is an adequate level of safety over the reference dose for possible endocrine effects and that an additional safety factor for possible endocrine effects is not warranted. C. Aggregate Exposure 1. Dietary exposure. An RfD of 0.01 mg/kg/day is proposed for humans, based on the NOAEL from the one year dog study (1 mg/kg/day) and dividing by an uncertainty factor of 100. i. Food--a. Acute risk. Tier 1 acute dietary exposure analyses were [[Page 76256]] conducted for fluazinam in/on peanuts, potatoes and imported wine grapes to determine the exposure contribution of these commodities to the diet and to ascertain the acute risk potential. The estimates were based on proposed tolerance level residues for all three crops, peanut and potato processing studies, market share assumptions of 100% crop treated, and consumption data from the 1994 through 1996 USDA continuing survey of food intake. Even using all of the worst case exposure scenarios listed above, the Tier 1 acute assessment for the U.S. population resulted in a margin of safety (MOS) of 270,507 at the 95th percentile. This corresponded to an estimated exposure of 0.000185 mg/kg/day. The highest acute exposure estimate (95th percentile) was observed in the seniors (55 years and over) subpopulation: 0.001285 mg/kg/day. This correlates to an MOE of 38,908. b. Chronic risk. Tier 1 dietary exposure analyses were conducted for fluazinam in/on peanuts, potatoes and imported wine grapes to determine the exposure contribution of these commodities to the diet and to ascertain the chronic risk potential. The estimates were based on proposed tolerance level residues for all three crops, peanut and potato processing studies, market share assumptions of 100% crop treated, and consumption data from the 1994 through 1996 USDA continuing survey of food intake. Even using all of the worst case exposure scenarios listed above, the Tier 1 chronic dietary exposure estimates resulted in an estimated exposure for the U.S. population of 0.000104 mg/kg/day. This exposure corresponds to 1.0% of the reference dose (RfD) of 0.01mg/kg/day. The highest exposure estimate was calculated for the Females 20+ years (non-pregnant/non-nursing) population subgroup. This exposure was determined to be 0.000156 mg/kg/day (1.6% of the RfD). It can be concluded that acute or long-term dietary exposure to fluazinam through residues on treated peanuts, potatoes and imported wine grapes should not be of cause for concern. ii. Drinking water. Since fluazinam is intended for application outdoors to field grown peanut and potato crops, the potential exists for parent and or metabolites to reach ground or surface water that may be used for drinking water. The calculated drinking water levels of concern (DWLOC) for chronic exposure for adult males, adult females and toddlers were estimated to be 355 parts per billion (ppb), 296 ppb, and 149 ppb, respectively. The calculated DWLOCs for acute exposure for all adults, adult females and toddlers were estimated to be 17,943 ppb, 14,993 ppb, and 7,497 ppb, respectively. The chronic and acute DWLOC values are well above the modeled chronic and acute DWECs of 0.17 ppb (GENEEC 56-day/3) and 15.1 ppb (GENEEC instantaneous value), respectively. Therefore, there is comfortable certainty that no harm will result from combined dietary (food and water) exposure due to the use of fluazinam on peanuts, potatoes and imported wine grapes. 2. Non-dietary exposure. No petition for registration of fluazinam is being made for either indoor or outdoor residential use. Non- occupational exposure of fluazinam to the general population is therefore not expected and is not considered in aggregate exposure estimates. D. Cumulative Effects Fluazinam is a phenylpyridinylamine fungicide. Since there are no other members of this class of fungicides, it is considered unlikely that fluazinam would have a common mechanism of toxicity with any other pesticide in use at this time. E. Safety Determination 1. U.S. population. Based on a NOAEL of 1 mg/kg bwt/day from a one year feeding study in dogs, and using an uncertainty factor of 100, a reference dose of 0.01 mg/kg bwt/day is proposed for assessment of long-term risk. The estimate of dietary intake was based on proposed tolerance level residues for all three crops, peanut and potato processing studies, market share assumptions of 100% crop treated and consumption data. Even using those conservative intake estimates, the proposed tolerances will utilize only 1% of the RfD for the U.S. population. The estimated exposure of fluazinam from drinking water, 0.17 ppb is at least three orders of magnitude below the calculated drinking water level of concern, 355 ppb. 2. Infants and children. Data from developmental toxicity studies in the rat and rabbit and a 2-generation reproduction study were considered. These studies which were described earlier, demonstrated no increased sensitivity of rats or rabbits to in utero exposure to fluazinam. In addition, the multigeneration reproductive toxicity study did not identify any increased sensitivity of rats to in utero or postnatal exposure. For all three studies, parental NOAELs were lower than or equivalent to the developmental or offspring NOAELs. It is concluded that the standard margin of safety will protect the safety of infants and children and that an additional safety factor is not warranted. The dietary exposure of fluazinam to infants and children is estimated to be much lower than adults because 80% to 90% of the exposure is expected from sherry and wine. The proposed tolerances will utilize 0.5% of the RfD for infants and children. The estimated exposure of fluazinam from drinking water, 0.17 ppb is three orders of magnitude below the calculated drinking water level of concern, 149 ppb. F. International Tolerances There are presently no Codex maximum residue levels established for residues of fluazinam on any crop.