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Flumetsulam (DowElanco). September 17, 1997. Pesticide Tolerance Petition. Federal Register.
http://www.epa.gov/fedrgstr/EPA-PEST/1997/September/Day-17/p24693.htm
[Federal Register: September 17, 1997 (Volume 62, Number 180)] [Notices] [Page 48842-48848] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr17se97-67] ----------------------------------------------------------------------- ENVIRONMENTAL PROTECTION AGENCY [PF-753; FRL-5735-5] 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-753, must be received on or before October 17, 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 [[Page 48843]] 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- Davis Hwy, mail:miller.joanne@ep Arlington, VA amail.epa.gov. Cynthia Giles-Parker (PM 22).. Rm. 229, CM #2, 703- Do. 305-7740, e-mail: giles- parker.cynthia@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-753] (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-753] 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: September 5,1997 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. 1. DowElanco PP 7F4851 EPA has received a pesticide petition (PP 7F4851) from DowElanco, 9330 Zionsville Road, Indianapolis, IN 46268-1054, 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 flumethsulam in or on the raw agricultural commodity dry beans at 0.05 ppm. The proposed analytical method involves homogenization, filtration, partition and cleanup with analysis by high performance liquid chromatography using UV 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 in plants is adequately understood. No metabolites of significance were detected in plant metabolism studies. 2. Analytical method. There is a practical analytical method for detecting and measuring levels of flumetsulam in or on food with a limit of quantitation (LOQ) of 0.010 ppm, and a limit of detection of 0.005 ppm that allows monitoring of food with residues at or above the levels set in these tolerances. EPA has provided information on this method to FDA. The method is availabe to anyone who is interested in pesticide residue enforcement. 3. Magnitude of residues. No detectable residues of flumetsulam were found in any of the drybean samples obtained from multiple sites and multiple varieties and analyzed using a method with a limit of detection of 0.005 ppm. B. Toxicological Profile 1. Acute toxicity. Flumetsulam has low acute toxicity. The rat oral LD50 is >5,000 mg/kg or greater for males and females. The rabbit dermal LD50 is >2,000 mg/kg and the rat inhalation LC50 is >1.2mg/L air (the highest attainable concentration). In addition, flumetsulam is not a skin sensitizer in guinea pigs, is not a dermal irritant and is not an ocular irritant. Therefore based on the available acute toxicity data, flumetsulam does not pose any acute dietary risks. 2. Genotoxicty. Flumetsulam is not genotoxic. The following studies have been conducted and all were negative for genotoxic responses: a dominant lethal assay, an In vivo rat cytogenic study, an In vitro Salmonella and Saccharomyces assay, an in vivo mouse host-mediated assay, and an unscheduled DNA synthesis assay in rats. 3. Reproductive and developmental toxicity. In a 2-generation reproduction study in rats, there was no compound-related reproductive toxicity. The No-Observed-Effect Level (NOEL) was greater than 1,000 mg/kg/day. Developmental toxicity was studied using rats and rabbits. The developmental study in rats resulted in a developmental NOEL greater than 1.000 mg/kg/day (highest dose tested) and a maternal NOEL of 500 mg/kg/day. A study in rabbits resulted in a [[Page 48844]] developmental NOEL equal to or greater than 700 mg/kg/day (highest dose tested) with a maternal NOEL of 100 mg/kg/day and a maternal LOEL (lowest observed effect level) of 500 mg/kg/day evidenced by decreased body weight gain. Based on all of the data for flumetsulam, there is no evidence of developmental toxicity at dose levels that do not result in maternal toxicity. 4. Subchronic toxicity . In a 13-week oral feeding study in mice at 5,000 mg/kg/day, slight effects on the liver, kidney, and cecum appeared to represent adaptive responses to treatment and have questionable toxicological significance. The NOEL was 1,000 mg/kg/day (limit dose). In a 13-week oral feeding study in dogs, the lowest- observed-effect level (LOEL) for both male and female dogs was 500 mg/ kg/day. A NOEL was not established for males or females. In a 13-week dietary study in rats, the NOEL was 250 mg/kg/day and the LOEL was 1,000 mg/kg/day. 5. Chronic toxicity. In a 1-year dietary study in dogs, the NOEL was 100 mg/kg/day and the LOEL was 500 mg/kg/day. The animals were administered feed containing 0, 20, 100, and 500 mg/kg/day. Reduced body weights and inflammatory and atrophic changes in the kidneys occurred in the 500 mg/kg/day dose groups. In a combined feeding carcinogenicity/chronic study in mice there were no treatment-related effects and there was no evidence of a carcinogenic response. Systemic NOEL was greater than or equal to 1,000 mg/kg/day (limit dose); a LOEL was not established. In a combined feeding carcinogenicity/chronic study in rats, renal pathological alterations were seen in males. No treatment-related effects were seen in females at the highest dose (1,000 mg/kg/day) which is the limit dose. There was no carcinogenic response. The NOELs were 500 mg/kg/day in males and 1,000mg/kg/day in females. The LOEL was 1,000 mg/kg/day in males; a LOEL was not established in females. Based on the chronic toxicity data, EPA has established the RfD for flumetsulam at 1.0 milligram (mg)/kilogram (kg)/day. The RfD for flumetsulam is based on the 1-year chronic study in dogs with a NOEL of 100 mg/kg/day and an uncertainty (or safety) factor of 100. Thus, it would not be necessary to require the application of an additional uncertainty factor above the 100-fold factor already applied to the NOEL. 6. Animal metabolism. Disposition and metabolism of flumetsulam were tested in male and female rats and male mice at an oral dose of 5 and 1,000 mg/kg for rats and 1,000 mg/kg for mice Flumetsulam was rapidly excreted. The majority of a radioactive dose was excreted in 48 hours of all dose groups. The principle route for elimination was the urine and to a lessor extent by fecal elimination. Detectable levels of residual radioactivity were observed in the carcass and stomach at 72 hours post-dose. HPLC and TLC analysis of urine and fecal extracts showed no apparent metabolism of flumetsulam. 7. Metabolite toxicology. There are no flumetsulam metabolites of toxicological significance. 8. Endocrine effects. There is no evidence to suggest that flumetsulam has an effectt on any endocrine system. C. Aggregate Exposure 1. Food. For purposes of assessing the potential dietary exposure under these tolerances, exposure is estimated based on the Theoretical Maximum Residue Contribution (TMRC) from the existing and pending tolerances for flumetsulam on food crops. The TMRC is obtained by multiplying the tolerance level residues by the consumption data which estimates the amount of those food products eaten by various population subgroups. Exposure of humans to residues could also result if such residues are transferred to meat, milk, poultry or eggs. The following assumptions were used in conducting this exposure assessment: 100% of the crops were treated, the RAC residues would be at the level of the tolerance, certain processed food residues would be at anticipated (average) levels based on processing studies and all current and pending tolerances were included. This results in an overestimate of human exposure and a conservative assessment of risk. Based on a NOEL of 100 mg/kg/day in a 1-year chronic feeding study in the dog and a hundredfold safety factor the reference dose (RfK) would be 1.0 mg/kg/ day. The TMRC for the general population would be 4.1 X 10-5 mg/kg/day or 0.0041% of the RfD. For non-nursing infants, the TMRC wold be 1.37 X 10-5 mg/kg/day or 0.014% of the RfD. 2. Drinking water. Another potential source of dietary exposure to residues of pesticides are residues in drinking water. There is no established Maximum Concentration Level for residues of flumetsulam in drinking water. Although there has been limited detections at ppb levels in some of the specially designed studies under highly vulnerable test conditions and at elevated non-labeled application rates, no ongoing monitoring studies, have reported residues of flumetsulam in ground or surface waters. Based on the physical and chemical characteristics of flumetsulam, such as water solubility and its stability under hydrolysis and photolysis, it has potential for downward movement through the soil profile. Degradation based on over 20 laboratory studies indicated a half-life range of 2 weeks to 4 months with 80% less than 2 months. Degradation is driven primarily by microbial processes. However based on the low application rate and detection in groundwater samples only under extremely vulnerable soil conditions at elevated non-labeled application rates with detections in single digit ppb levels, flumetsulam is not anticipated to be a groundwater contaminant. In summary, these data on potential water exposure indicate insignificant additional dietary intake of flumetsulam and any exposure is more than compensated for in the conservative dietary risk evaluation. Therefore, it is concluded that there is a reasonable certainty of no harm even at potential upper limit exposures to flumetsulam from drinking water. 3. Non-dietary exposure. There are no non-dietary uses for flumetsulam registered under the Federal Insecticide, Fungicide and Rodenticide Act. Potential exposures for children is therefore limited to dietary exposure. D. Cumulative Effects The potential for cumulative effects of flumetsulam and other substances that have a common mechanism of toxicity was considered. The mammalian toxicity of flumetsulam is well defined. However, no reliable information exists to indicate that toxic effects produced by flumetsulam would be cumulative with those of any other chemical compound. Additionally, flumetsulam does not appear to produce a toxic metabolite produced by other substances. Therefore, consideration of a common mechanism of toxicity with other compounds is not appropriate at this time. Thus only the potential exposures to flumetsulam were considered in the aggregate exposure assessment. E. Safety Determination 1. U.S. population. Based on a NOEL of 100 mg/kg/bwt/day from a one-year dog feeding study with a reduced weight and inflammatory and atrophic kidney effect, and using an uncertainty factor of 100 to account for the interspecies extrapolation and intraspecies variability, a Reference Dose (RfD) of 1.0 mg/kg bwt/day was used for this assessment of chronic risk. As indicated, there is no endpoint of concern identified with acute and short-or intermediate-term exposures. The existing and proposed tolerances [[Page 48845]] would utilize 0.000041 mg/kg bwt/day or less than 0.01% of the RfD for the U.S. population. And, as indicated previously, whatever upper limit might be used for drinking water exposure, the exposure estimate for flumetsulam would not exceed the RfD. Generally, exposures below 100 percent of the RfD are of no concern because the RfD represents the level at or below which daily aggregate dietary exposure over a lifetime will not pose appreciable risk to human health. Thus, there is a reasonable certainty that no harm will result from aggregate exposure to flumetsulam residues. 2. Infants and children. In assessing the potential for additional sensitivity of infants and children to residues of flumetsulam, data from developmental toxicity studies in the rat and rabbit and a 2- generation reproduction study in the rat were considered. The developmental toxicity studies are designed to evaluate adverse effects on the developing organism during prenatal development resulting from pesticide exposure to one or both parents. Reproduction studies provide (1) information relating to effects from exposure to the pesticide on the reproductive capability of mating animals and (2) data on systemic toxicity. As indicated previously, reproductive and developmental toxicity was studied using rats and rabbits. The data base is complete and based on all of the data for flumetsulam, there is no evidence of reproductive or developmental toxicity at dose levels that do not result in maternal toxicity. 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. These data suggest minimal concern for developmental or reproductive toxicity and do not indicate any increased pre- or post- natal sensitivity. Therefore, an additional uncertainty factor is not necessary to protect the safety of infants and children and that the RfD at 1.0 mg/kg/day is appropriate for assessing aggregate risk to infants and children. The percent of the RfD that will be utilized by the aggregate exposure from all tolerances to flumetsulamill be less than 0.1% for non-nursing infants and for children (1-6 years of age). Therefore, based on the completeness and reliability of the toxicity data and the conservative exposure assessment, it is concluded that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to flumetsulam residues. F. International Tolerances There are no Codex maximum residue levels established for flumetsulam. (Joanne Miller) [FR Doc. 97-24693 Filed 9-16-97; 8:45 am] BILLING CODE 6560-50-F