FLUORIDE ACTION NETWORK PESTICIDE PROJECT
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Fluroxypyr
1-methylheptyl ester
Fluroxypyr
Fluroxypyr (DowElanco). December 17, 1997. Pesticide Tolerance Petition. Federal Register.
Note from EC:
There were 3 pesticide petitions included in this Notice. We only include the fluorinated Fluroxypyr.
http://www.epa.gov/fedrgstr/EPA-PEST/1997/December/Day-17/p32936.htm
[Federal Register: December 17, 1997 (Volume 62, Number 242)] [Notices] [Page 66083-66091] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr17de97-73] ----------------------------------------------------------------------- ENVIRONMENTAL PROTECTION AGENCY [PF-782; FRL-5759-1] 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-782, must be received on or before January 16, 1998. ADDRESSES: By mail submit written comments to: Public Information and Records Integrity Branch (7502C), 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 to: opp- docket@epamail.epa.gov. Follow 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 ------------------------------------------------------------------------ Joanne Miller (PM 23)......... Rm. 237, CM #2, 703- 1921 Jefferson 305-6224, e-mail: Davis Hwy, miller.joanne@epamail Arlington, VA .epa.gov. James Tompkins (PM 25)........ Rm. 239, CM #2, 703- Do. 305-5697, e-mail: tompkins.james@epamai l.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-782] (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 5.1/6.1 or ASCII file format. All comments and data in electronic form must be identified by the docket control number [PF-782] 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: December 3, 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. [[Page 66084]] 1. DowElanco PP 6F4772 EPA has received a pesticide petition (PP 6F4772) from DowElanco, 9330 Zionsville Road, Indianapolis, IN 46268, 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 fluroxypyr methylheptyl ester (MHE) and its only significant metabolite fluroxypyr, free and conjugated, all expressed as fluroxypyr in or on the raw agricultural commodities wheat, barley, and oats as follows: 0.5 parts per million (ppm) (grain), 10 ppm (straw and forage), 20 ppm (hay), and 0.5 ppm (aspirated grain fractions, wheat). Because residues of fluroxypyr MHE or fluroxypyr, free or conjugated, may occur in animal feeds derived from wheat, barley, and oats, the following meat and milk tolerances are also being proposed: 0.1 ppm (meat, fat, milk, and meat byproducts except for kidney) and 0.5 ppm (kidney). The proposed analytical method is based on gas chomatography (GC) with mass spectral (MS) detection. 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 fluroxypyr MHE in plants (wheat) and animals (goats and poultry) is adequately understood for the purposes of this tolerance. A rotational crop study showed no carryover of significant fluroxypyr MHE related residues in representative test crops except for cereal grains for which tolerances are being proposed. 2. Analytical method. There is a practical method (GC with MS detection) for measuring levels of fluroxypyr MHE in or on food with a limit of detection that allows monitoring of food with residues at or above the levels set for the proposed tolerances. Fluroxypyr has been tested through the FDAs Multiresidue Methodology, Protocols C, D. and E. The results have been published in the FDA Pesticide Analytical Manual, Volume I. 3. Magnitude of residues. Magnitude of residue studies were conducted for wheat, barley, and oats. Residues of fluroxypyr MHE did not concentrate in process fractions in samples treated at a 7.5 X application rate. B. Toxicological Profile 1. Acute toxicity. Fluroxypyr MHE has low acute toxicity. The rat oral LD<INF>50</INF> is >5000 mg/kg, the rabbit dermal LD<INF>50</INF> is >2000 mg/kg, and the rat inhalation LC<INF>50</INF> is >1.0 mg/l (1,000 mg/cubic meter), the maximum attainable concentration. In addition, fluroxypyr MHE is not a skin sensitizer in guinea pigs, has no dermal irritation in rabbits, and shows mild ocular irritation in rabbits. The end use formulation of fluroxypyr MHE has a similar low acute toxicity profile. 2. Genotoxicity. Short term assays for genotoxicity consisting of a bacterial reverse mutation assay (Ames test), an in vitro assay for cytogenetic damage using the Chinese hamster ovary cells, an in vitrochromosomal aberration assay using rat lymphocytes, and an in vivo cytogenetic assay in the mouse bone marrow (micronucleus test) have been conducted with fluroxypyr MHE. DowElanco believes that these studies show a lack of genotoxicity. In addition, short term assays for genotoxicity consisting of an Ames metabolic activation test, point mutations at the HGPRT-Locus of Chinese hamster ovary cells, in vivo and in vitro chromosomal aberrations in the Chinese hamster ovary cells, unscheduled DNA synthesis in human embryonic cells, and an assay in mouse lymphoma cells have been conducted with fluroxypyr. DowElanco believes that the weight of evidence also indicates a lack of genotoxicity. 3. Reproductive and developmental toxicity. Developmental studies in rats and rabbits were conducted with both fluroxypyr MHE and fluroxypyr. Studies with fluroxypyr MHE showed maternal and fetal no observed effect levels (NOELs) of 300 milligram/kilogram (mg/kg/day) (rat) and 500 mg/kg/day (rabbit). Studies with fluroxypyr showed no observed adverse effect levels (NOAELs) in the rat of 250 mg/kg/day for maternal effects and 500 mg/kg/day for fetal effects and a NOEL in the rabbit of 250 mg/kg/day for both maternal and fetal effects. DowElanco believes that these studies show that fluroxypyr and fluroxypyr MHE are not teratogenic nor will they interfere with in utero development. Two multi-generation reproduction studies were conducted with fluroxypyr in rats. The first in Wistar rats showed no effect on fertility or reproductive performance and had a NOAEL of 500 mg/kg/day (highest dose tested). The second study in Sprague-Dawley rats showed a parental NOEL for systemic effects of 100 mg/kg/day in male rats and 500 mg/kg/day in female rats. The NOEL for reproductive effects was 750 mg/kg/day for males and 1,000 mg/kg/day for females (highest dose tested). The NOEL for neonatal effects was 500 mg/kg/day. 4. Subchronic toxicity. Fluroxypyr MHE showed a NOEL of 1,000 mg/ kg/day in a 90-day rat dietary study and a 21-day rabbit dermal study. Ninety day feeding studies with fluroxypyr showed NOELs of 80 mg/kg/day (Wistar rats), 700 mg/kg/day (Fischer 344 rats), 1342 mg/kg/day (male mice), and 1,748 mg/kg/day (female mice). In a 4-week dietary, range finding study with fluroxypyr in dogs the NOEL was >50 mg/kg/day. 5. Chronic toxicity. Based on chronic testing with fluroxypyr in the mouse, dog, and rat (two studies), a reference dose (RfD) of 0.8 mg/kg/day is proposed for fluroxypyr and fluroxypyr MHE. The RfD has incorporated a 100-fold safety factor to the NOEL found in the rat chronic test. NOELs found in the chronic dietary studies are as follows: 150 mg/kg/day (dog), 300 mg/kg/day (mouse), 80 mg/kg/day (Wistar rats), 100 mg/kg/day (male Fischer 344 rats), and 500 mg/kg/day (female Fischer 344 rats). 6. Animal metabolism. Both fluroxypyr and fluroxypyr MHE have been evaluated in rat metabolism studies. In summary, these studies show that fluroxypyr MHE is rapidly hydrolyzed and the fate of the hydrolysis products, fluroxypyr and 1-methylheptanol, are independent of whether they were given as the ester or the acid. Fluroxypyr, per se, was extensively absorbed and rapidly excreted principally unchanged in the urine. 1-Methylheptanol also was rapidly absorbed and rapidly eliminated. Repeated administration of fluroxypyr MHE was not associated with accumulation in tissues. Also, the metabolism and pharmacokinetics of methylheptanol are comparable to that of the methylheptyl portion of fluroxypyr MHE. 7. Metabolite toxicology. Administration of fluroxypyr, as the acid or methylheptyl ester, in a variety of toxicological studies has produced similar effects. The principal response to sufficiently high dosages, whether administered over the short-term or, in some cases, over a lifetime, was nephrosis. Fluroxypyr is an organic acid that is actively excreted into the urine by the kidney. Thus, the target organ and dose response relationship for fluroxypyr toxicity are entirely consistent with the data on the toxicokinetics of fluroxypyr. Metabolism studies have shown that fluroxypyr MHE is rapidly and completely hydrolyzed to fluroxypyr acid and methylheptanol. [[Page 66085]] 8. Carcinogenicity. Using the Guidelines for Carcinogen Risk Assessment published September 24, 1986 (51 FR 33992), it is proposed that fluroxypyr and fluroxypyr MHE be classified as Group E for carcinogenicity (no evidence of carcinogenicity) based on the results of carcinogenicity studies in two species. DowElanco believes that there was no evidence of carcinogenicity in an 18-month mouse feeding study and a 24-month rat feeding study at all dosages tested. The NOELs shown in the mouse and rat oncogenicity studies were 1,000 and 320 mg/ kg/day, respectively. A maximum tolerated dose was achieved at the top dosage level tested in both of these studies based on excessive renal toxicity. Thus, the doses tested are adequate for identifying a cancer risk. Accordingly, DowElanco believes that a cancer risk assessment is not needed. 9. Endocrine effects. There is no evidence to suggest that fluroxypyr and fluroxypyr HME have an effect on any endocrine system. C. Aggregate Exposure 1. Dietary exposure--i. Food. An over estimation of dietary exposure from use of fluroxypyr MHE on wheat, barley, oats is determined by basing the TMRC on the conservative assumptions that all cereal grain commodities will have tolerance level residues of fluroxypyr and that 100% of the wheat, barley, and oat crops grown in the U.S. are treated with fluroxypyr MHE. The TMRC is obtained by multiplying the tolerance residue levels by the consumption data which estimates the amount of crops and related foodstuffs consumed by various population subgroups. There are no other established U.S. tolerances or exemption from tolerances for fluroxypyr MHE and no other registered uses for fluroxypyr MHE on food or feed crops in the United States. The use of a tolerance level and 100% of crop treated clearly results in an overestimate of human exposure and a safety determination for the use of fluroxypyr MHE on wheat, barley, and oats that is based on a conservative exposure assessment. ii. Drinking water. Another potential source of dietary exposure are residues in drinking water. Based on the available environmental studies conducted with fluroxypyr MHE and fluroxypyr wherein the properties of these materials show little persistence in the soil environment, there is no anticipated exposure to residues of fluroxypyr MHE and fluroxypyr in drinking water. In addition, there is no established Maximum Concentration Level for residues of fluroxypyr MHE and fluroxypyr in drinking water. 2. Non-dietary exposure. There are no other uses currently registered for fluroxypyr MHE and fluroxypyr. The proposed use on wheat, barley, and oats involves application of fluroxypyr MHE to crops grown in an agriculture environment. Thus, the potential for non- occupational exposure to the general population is not expected to be significant. D. Cumulative Effects The potential for cumulative effects of fluroxypyr MHE and fluroxypyr and other substances that have a common mechanism of toxicity is also considered. There is no reliable information to indicate that toxic effects produced by fluroxypyr MHE and fluroxypyr would be cumulative with those of any other pesticide chemical. Thus, it is appropriate to consider only the potential risks of fluroxypyr MHE and fluroxypyr in an aggregate exposure assessment. E. Safety Determination 1. U.S. population. Using the conservative exposure assumptions and the proposed RfD, the dietary exposure to fluroxypyr MHE use on wheat, barley, and oats will utilize 0.2% of the RfD for the U.S. 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. Since there are no anticipated residues in drinking water or from other non-occupational sources and no reliable information exists on cumulative effects due to common mechanism of toxicity, the aggregate exposure to fluroxypyr MHE is adequately represented by the dietary route. Thus, DowElanco believes that there is reasonable certainty that no harm will result from aggregate exposure to fluroxypyr MHE residues on wheat, barley, and oats. 2. Infants and children. In assessing the potential for additional sensitivity of infants and children to residues of fluroxypyr MHE, data from developmental toxicity studies in rats and rabbits and a 2- generation 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. 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 pups. 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 for fluroxypyr MHE relative to pre- and post-natal effects for children is complete. Further, for fluroxypyr MHE, the NOEL in the chronic feeding studies which was used to calculate the RfD (0.8 mg/kg/ day) is already lower than the NOELs from the developmental studies in rats and rabbits by a factor of more than three. Concerning the reproduction studies in rats, the pup effects shown at the highest dose tested (1,000 mg/kg/day) were attributed to maternal toxicity. Therefore, DowElanco concludes that an additional uncertainty factor is not needed and that the RfD at 0.8 mg/kg/day is appropriate for assessing risk to infants and children. As noted above for the general U.S. population, aggregate exposure for infants and children will result from the dietary (i.e. not drinking water or non-occupational) route of exposure. In addition, there is no reliable information that shows cumulative effects based on a common mechanism of toxicity for infants and children. Using the conservative exposure assumptions previously described, the percent RfD utilized by the aggregate dietary exposure to residues of fluroxypyr MHE on wheat, barley, and oats is 0.6% for children 1 to 6 years old, the most sensitive population subgroup. Thus, based on the completeness and reliability of the toxicity data and the conservative exposure assessment, DowElanco believes that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to fluroxypyr MHE residues on wheat, barley, and oats. F. International Tolerances There are no Codex maximum residue levels established for residues of fluroxypyr MHE and fluroxypyr on any food or feed crop. (J. Miller) [FR Doc. 97-32936 Filed 12-16-97; 8:45 am] BILLING CODE 6560-50-F