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Carfentrazone-ethyl (FMC). May 16, 1997. Pesticide Petition for Temporary Tolerances. Federal Register.
http://www.epa.gov/docs/fedrgstr/EPA-PEST/1997/May/Day-16/p12911.htm
[Federal Register: May 16, 1997 (Volume 62, Number 95)] [Notices] [Page 27040-27043] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr16my97-66] ----------------------------------------------------------------------- ENVIRONMENTAL PROTECTION AGENCY [PF-732; FRL-5717-4] 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-732, must be received on or before June 16, 1997. ADDRESSES: By mail submit written comments to: Public Information and Records Integrity Branch, Information Resources and Services Division (7506C), 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: By mail: Joanne Miller, PM 23, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. Office location and telephone number: Rm. 237, CM #2, 1921 Jefferson Davis Hwy, Arlington, VA 22202, 703-305-6224, e-mail: miller.joanne@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-732] (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 [PF-732] 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: May 7, 1997. James Jones, 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. FMC Corporation PP 6G4615 EPA has received a pesticide petition (PP 6G4615) from FMC Corporation, 1735 Market St., Philadelphia, PA 19103, 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 temporary tolerance for the combined residue of the herbicide carfentrazone-ethyl (ethyl--2-dichloro-5-[4-(difluoromethyl)- 4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzene- propanoate) and its major wheat metabolites: carfentrazone-ethyl chloropropionic acid ( , 2-dichloro-5-[4-difluoromethyl)-4,5- dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzenepropanoic acid), 3-hydroxymethyl-F8426-chloropropionic acid ( , 2- dichloro-5-[4-difluoromethyl)-4,5-dihydro-3-hydroxymethyl-5-oxo-1H- 1,2,4-triazol-1-yl]-4-fluorobenzenepropanoic acid) and 3-desmethyl- F8426 chloropropionic acid ( , 2-dichloro-5-[4-difluoromethyl)- 4,5-dihydro-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzenepropanoic acid) in or on wheat raw agricultural commodities: 0.2 ppm in or on wheat hay, 0.2 ppm in or on wheat straw, 0.2 ppm in or on wheat grain; and establishing tolerance for combined residues of the herbicide carfentrazone-ethyl (ethyl- -2-dichloro-5-[4-(difluoromethyl)- 4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzene- propanoate) and its two major corn metabolites: carfentrazone- [[Page 27041]] ethyl chloropropionic acid ( , 2-dichloro-5-[4- difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4- fluorobenzenepropanoic acid), and 3-desmethyl-F8426 chloropropionic acid ( , 2-dichloro-5-[4-difluoromethyl)-4,5-dihydro-5-oxo-1H- 1,2,4-triazol-1-yl]-4-fluorobenzenepropanoic acid) in or on corn raw agricultural commodities: 0.15 ppm in or on corn forage, 0.15 ppm in or on corn fodder, 0.15 ppm in or on corn grain. EPA has determined that the petition 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 petitions. Additional data may be needed before EPA rules on the petitions. The proposed analytical method is GC-MS and is available for enforcement purposes. As required by section 408(d) of the FFDCA, as recently amended by the Food Quality Protection Act (FQPA) FMC included in the petition a summary of the petition and authorization for the summary to be published in the Federal Register in a notice of the receipt of the petition. The summary represents the views of FMC; EPA 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. Carfentrazone-ethyl is a postemergent herbicide which controls a broad spectrum of broadleaf weeds at very low field application rates. Carfentrazone-ethyl is particularly effective on Velvetleaf (Abutilon theophrasti), Russian Thistle (Salsola kali), Pigweeds (Amaranthus spp.), Morningglories (Ipomea spp.), Lambsquarters (Chenopodium album) and Black Nightshade (Solanum nigrum). It is also effective on sulfonylurea-resistant populations of important weeds such as Kochia (Kochia scoparia) and Russian Thistle (Salsola kali) and on imidazolinone- or sulfonylurea-resistant populations of pigweeds. Use site: Corn: Broadleaf weeds (including cocklebur, lambsquarters, morningglories, pigweeds, nightshades and velevetleaf); Wheat: Broadleaf weeds (including wild buckwheat, kochia, lambsquarters, mustards, nightshades, pigweeds, Russian thistle and waterhemp). Use pattern: Carfentrazone-ethyl herbicide is applied postemergence to young actively growing weeds that have emerged from the soil. Typically, the crop has less than eight leaves, and the weeds are less than four inches tall when the product is applied. Crops such as corn and wheat are tolerant to the product at use rates which control selected weeds. The product is mixed in water or liquid nitrogen fertilizer used as the carrier. A nonionic surfactant or liquid nitrogen fertilizer is mixed with the spray solution to enhance weed control. Spray volumes range from 5-40 gallons per acre. Other herbicides may be tank mixed with carfentrazone-ethyl to broaden the weed control spectrum. A. Residue Chemistry 1. Plant metabolism. The qualitative nature of the residues in plants and animals is adequately understood. Residues of carfentrazone- ethyl do not concentrate in the processed commodities. There are no Codex maximum residue levels established for residues of carfentrazone- ethyl on wheat, corn or soybeans. 2. Analytical method. There is a practical analytical method available using GC-MS, for detecting and measuring levels of carfentrazone-ethyl in or on food with a limit of detection that allows monitoring of food with residues at or above the levels set in these tolerances. 3. Magnitude of the residue-- i. Wheat. F8426 50DF was applied to 28 wheat trials in the major wheat growing regions of the United States. Trials were conducted on both winter wheat (16 trials) and spring wheat (12 trials). Forage samples had total residues ranging from ND (<0.1 ppm) to 0.64 ppm. The maximum total residue in/on any hay sample was 0.24 ppm. The maximum total residue found on any straw sample was an estimated 0.05 ppm. No detectable residues (>0.01 ppm) of carfentrazone-ethyl or any of its metabolites were found in/on any grain sample. No detectable residues (>0.01 ppm) of carfentrazone-ethyl or its metabolites were found in any of the treated wheat grain or processed commodities. Based on these results, there was no concentration of carfentrazone-ethyl or its acid metabolites into any of the processed parts. ii. Corn. Twenty four field corn trials were conducted in the major corn growing regions of the continental United States with F8426 50DF. No quantifiable residues (>0.05 ppm) of carfentrazone-ethyl or any of its metabolites were found in the analyses of the treated forage, fodder and grain samples except for two forage samples which had residues of 0.05 and 0.10 ppm. The maximum total residue in/on any corn forage sample was 0.10 ppm and on any fodder and grain sample was an estimated 0.01 ppm. No detectable residues of carfentrazone-ethyl or its metabolites were found in any fraction of corn treated. Based on the residue results, there was no concentration of carfentrazone-ethyl and its metabolites into any of the processed parts. 4. Animal feeding. There is no need for tolerances in animal meat, milk, poultry or eggs since there is no reasonable expectation of residues in these materials. This is based on the results of cow feeding and poultry metabolism studies, as well as the plant metabolism and crop rotation studies. Transfer factors are extremely low and maximum expected total residues in meat, milk, poultry and eggs would be below the method limit of detection (LOD). The LOD of the methods is, therefore, higher than any individual analyte in any of the matrices. Based on this, since there is no expectation of finite residues in meat, milk, poultry and eggs, no tolerances are being proposed for these commodities. The proposed crop tolerance levels are adequate to cover residues likely to be present from the proposed use of carfentrazone-ethyl. Therefore, no special processing to reduce the residues will be necessary. B. Toxicological Profile EPA has reviewed and accepted over 20 separate toxicology studies in support of temporary tolerances for carfentrazone-ethyl; additional studies have been submitted to EPA for review. Carfentrazone-ethyl is not a carcinogen, developmental toxin or a mutagen and has low oral and dermal toxicity to mammals. The following mammalian toxicity studies have been conducted to support the tolerance of carfentrazone-ethyl: A rat acute oral study with an LD 50 of greater than 5,000 mg/kg(male) and 5,143 mg/kg (female). A rat acute dermal LD50 of greater than 4,000 mg/kg. A rat acute inhalation LC50 of greater than 5.09 mg/L/4 hour. A primary eye irritation study in rabbits which showed minimal irritation. A primary dermal irritation study in rabbits which showed no irritation. A primary dermal sensitization study which showed no sensitization. An acute neurotoxicity study in the rat with a systemic NOAEL of 500 mg/kg; the NOAEL for neurotoxicity was greater than 2,000 mg/kg (highest dose tested). A 28-day feeding study in the rat with a NOEL of 1,000 ppm (74.6 mg/kg/ [[Page 27042]] day for males; 85.2 mg/kg/day for females). A 90-day feeding study in the rat with a NOEL of 1,000 ppm (57.9 mg/kg/day for males; 72.4 mg/kg/day for females). A 28-day feeding study in the mouse with a NOEL of 4,000 ppm (571 mg/kg/day) for males and a NOEL of 1,000 ppm (143 mg/kg/day) for females. A 90-day feeding study in the mouse with a NOEL of 4,000 ppm (approximately 571 mg/kg/day). A 90-day subchronic neurotoxicity study in the rat with a systemic NOEL of 1,000 ppm (59.0 mg/kg/day for males; 70.7 mg/kg/day for females); the neurotoxicity NOEL was greater than 20,000 ppm (1178.3 mg/kg/day for males; 1433.5 mg/kg/day for females) which was the highest dose tested. A 24-month chronic feeding/oncogenicity study in the rat with a chronic toxicity NOEL of 200 ppm (9 mg/kg/day) in the male and 50 ppm (3 mg/kg/day) in the female. There was no evidence of an oncogenic response. A 4-week range-finding study in dogs confirmed that the appropriate route of administration was by capsule and the top dose selected for the 3-month study was the limit dose of 1,000 mg/kg/day. A 90-day feeding study in dogs with a NOEL of 150 mg/kg/day for both males and females. A 12-month feeding study in dogs with a NOEL of 50 mg/kg/day. A mouse oncogenicity study with a carcinogenic NOEL greater than 7,000 ppm (greater than 1,090 mg/kg/day for males; greater than 1,296 mg/kg/day for females) based on no evidence of carcinogenicity at the highest dose tested. An oral teratology study in the rat with a maternal NOEL of 100 mg/ kg/day; the developmental NOAEL was greater than 1,250 mg/kg/day. An oral teratology study in the rabbit with a maternal NOEL of 150 mg/kg/day; the fetal NOEL was greater than 300 mg/kg/day (highest dose tested) since no fetal effects were observed. A 2-generation reproduction study in the rat with a NOAEL for systemic toxicity of 500 ppm (P1: 120 mg/kg/day for males and 137 mg/ kg/day for females; F1: 134 mg/kg/day for males and 146 mg/kg/day for females); the reproductive NOEL was greater than 4,000 ppm (P1: greater than 323 mg/kg/day for males and greater than 365 mg/kg/day for females; F1: greater than 362 mg/kg/day for males and greater than 409 mg/kg/day for females) since reproductive parameters were not affected at the highest dose tested in the study. The weight of the evidence of the mutagenicity database including the following is that carfentrazone-ethyl is not mutagenic. Ames Assay: Negative. Mouse Micronucleus Assay: Negative. In vitro Chromosome Aberration - Negative with activation; Positive without activation. CHO/HGPRT Forward Mutation Assay - Negative. Unscheduled DNA Synthesis - Negative. C. Aggregate Exposure For purposes of assessing the potential dietary exposure, a preliminary dietary risk assessment was conducted based on the Theoretical Maximum Residue Contribution (TMRC) from the tolerances for carfentrazone-ethyl on soybeans at 0.1 ppm, wheat at 0.2 ppm and corn (field) at 0.15 ppm. (The TMRC is a ``worse 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 present at the tolerance levels.) At this time the dietary exposure to residues of carfentrazone-ethyl in or on food will be limited to residues on soybeans, wheat and corn. There are no other established US tolerances for carfentrazone-ethyl, and there are no registered uses for carfentrazone-ethyl on food or feed crops in the US. In conducting this exposure assessment, the following very conservative assumptions were made--100 percent of soybeans, wheat and corn will contain carfentrazone-ethyl residues and those residues would be at the level of the tolerance which result in an overestimate of human exposure. Other potential sources of general population exposure to residues of pesticides are residues in drinking water and exposure from non- occupational sources. Studies have indicated that carfentrazone-ethyl will not move into groundwater. There is no expectation of non-occupational exposure from any other source since the current registration application is the first for carfentrazone-ethyl and is limited to commercial production of corn and wheat. The potential for non-occupational exposure to the general population is, thus, insignificant. EPA is also required to consider the potential for cumulative effects of carfentrazone ethyl and other substances that have a common mechanism of toxicity. EPA consideration of a common mechanism of toxicity is not appropriate at this time since EPA does not have information to indicate that toxic effects produced by carfentrazone- ethyl would be cumulative with those of any other chemical compounds; thus only the potential risks of carfentrazone-ethyl are considered in this exposure assessment. Chronic dietary effects. Based on the available toxicity data, FMC believes that the Reference Dose (RfD) for carfentrazone-ethyl is 0.03 milligrams(mg)/kilogram(kg)/day. The RfD for carfentrazone-ethyl is based on the chronic feeding/oncogenicity study in rats with a threshold No-Observed Effect Level (NOEL) of 3 mg/kg/day and an uncertainty factor of 100. EPA recently proposed a tiered approach to estimate acute dietary exposure. The methods proposed by the EPA were reviewed and supported by the FIFRA scientific advisory panel (SAP, 1995). EPA's Tier 1 method is based on the assumption that residue concentrations do not vary. The analysis assumes that all residues have the same magnitude, typically the highest field trial residue or tolerance value. This value is assumed for all points along the consumption distribution, resulting in a distribution of dietary exposure. For the acute analysis for carfentrazone-ethyl, a Tier 1 analysis was conducted for the overall US population, infants and children 1 to 6 years of age. The analysis incorporated anticipated residue estimates of 0.1 ppm for soybeans, wheat and corn including sweet and pop corn. A NOEL of 3 mg/kg /day with a 100-fold uncertainty factor was used in the calculation. This NOEL was derived from the chronic rat feeding study and represents an extremely excessive worst case scenario. The following margins of exposure (MOE) were calculated (margins of exposure of 100 or more are considered satisfactory): ------------------------------------------------------------------------ Population Group Margin of Exposure ------------------------------------------------------------------------ US Population 3516 Infants 1804 Children 1 to 6 2057 ------------------------------------------------------------------------ These MOEs show that there is no acute dietary risk from carfentrazone-ethyl. Using the Guidelines for Carcinogen Risk Assessment, carfentrazone-ethyl should be classified as Group ``E'' for carcinogenicity -- no evidence of carcinogenicity -- based on the results of carcinogenicity studies in two species. There was no evidence of carcinogenicity in an 18-month feeding study in mice and a 2-year feeding study in rats at the dosage levels tested. The doses tested are adequate for identifying a cancer risk. Thus, a cancer risk assessment is not necessary. Using [[Page 27043]] the conservative exposure assumptions described and based on the completeness and reliability of the toxicity data, the aggregate exposure to carfentrazone-ethyl will utilize 0.61 percent of the RfD for the US 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, FMC believes that there is a reasonable certainty that no harm will result from aggregate exposure to residues of carfentrazone- ethyl, including all anticipated dietary exposure and all other non- occupational exposures. D. Determination of Safety for Infants and Children In assessing the potential for additional sensitivity of infants and children to residues of carfentrazone-ethyl, EPA considers data from developmental toxicity studies in the rat and rabbit and the 2- generation reproduction study in the rat. The developmental toxicity studies are designed to evaluate adverse effects on the developing organism resulting from pesticide exposure during prenatal development. Reproduction studies provide information relating to effects on the reproductive capacity of males and females exposed to the pesticide. Developmental toxicity was not observed in developmental toxicity studies using rats and rabbits. In these studies, the rat and rabbit maternal NOELs were 100 mg/kg/day and 150 mg/kg/day, respectively. The developmental NOEL for the rabbit was greater than 300 mg/kg/day which was the highest dose tested and for the rat was 600 mg/kg/day based on increased litter incidences of thickened and wavy ribs. These two findings are not considered adverse effects of treatment but related delays in rib development which are generally believed to be reversible. In a 2-generation reproduction study in rats, no reproductive toxicity was observed under the conditions of the study at 4,000 ppm which was the highest dose tested. 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 database. Based on the current toxicological data requirements, the database relative to pre- and post-natal effects for children is complete and an additional uncertainty factor is not warranted. Therefore, the RfD of 0.03 mg/kg/ day is appropriate for assessing aggregate risk to infants and children. Using the conservative exposure assumptions described above, the percent of the RfD that will be utilized by aggregate exposure to residues of carfentrazone-ethyl for non-nursing infants (<1 year old) would be 0.38 percent and for children 1-6 years of age would be 1.56 percent (the most highly exposed group). Based on the completeness and reliability of the toxicity data and the conservative exposure assessment, FMC believes that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the residues of carfentrazone-ethyl including all anticipated dietary exposure. E. Estrogenic Effects No specific tests have been conducted with carfentrazone-ethyl to determine whether the pesticide may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen. [FR Doc. 97-12911 Filed 5-15-97; 8:45 am] BILLING CODE 6560-50-F