EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER I nterregional Research Project Number 4 (I R
- 4 ) Petition #5E8395 EPA has received a pesticide petition ( PP #5E8395 ) from IR
- 4, IR
- 4 Project, 500 College Road East, Suite 201W Princeton, NJ 08540 , 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 tolerance s for residues of fomesafen, 5
- [2
- cloro
- 4
- (trifluoromethyl)phenoxy]
- N
- (methylsulfonyl)
- 2
- nitrobenzamide in or on the raw agricultural commodit ies Vegetable, tuberous and corm, subgroup 1C at 0.025 parts per million (ppm) , Berry , low growing subgroup 13
- 07G, except cranberry at 0.02 ppm , and Vegetable, legume group 6 at 0 .05 ppm . Upon the approval of the aforementioned tolerances, IR
- 4 proposes to remove the established tolerances for fomesafen, 5
- [2
- cloro
- 4
- (trifluoromethyl)phenoxy]
- N
- (methylsulfonyl)
- 2
- nitrobenzamide in or on the raw agricultural commodities Bean, dry at 0.05 ppm; Bean, snap, succulent at 0.05 ppm; Bean Lima, succulent at 0.05 ppm; Pea, succulent at 0.025 ppm; Potato at 0.025 pp m; Soybean at 0.05 ppm; and Soybean, vegetable succulent at 0.05 ppm. EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency o f 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. Cotton , soybean and tomato metabolism studies were conducted using 14 C
- labeled fomesafen. The major degradation pathway of fomesafen in these commodities involves ether cleavage followed by cystine conjugation. The major portion of the applied chemical is comprised of unchanged fom esafen. Metabolites, if present , are <0.01 mg/kg. Very little translocation from treated foliage tissue occurs. The nature of the residue is adequately understood. 2. Analytical method. An analytical method using chemical derivatization followed by gas c hromatography with Nitrogen
- Phosphorus detection (NPD) has been developed and validated for residues of fomesafen in snap/dry beans, cotton seed and cotton gin byproducts, as well as for other crops. After homogenization, the samples are extracted with aci dified acetonitrile. After addition of water and additional acid, the extract is submitted to liquid/liquid partition. The residue is transferred to dichloromethane, followed by acetone and derivatized with iodomethane in the presence of anhydrous potassiu m carbonate. A silica gel column cleanup is done, with dichloromethane:hexane as the eluent. The final extract is transferred to toluene and2

analyzed by GC
- NPD. The limit of quantitation is 0.025 ppm. 3. Magnitude of residues. M agnitude of the residue studies supporting the currently established tolerances of 0.05 ppm for fomesafen on beans (dry and snap, succulent (edible podded)), 0.025 ppm on pea (succulent with and without pod), and 0.05 ppm on soybean have been previously submitted and evaluated by the United States Environmental Protection Agency . An additional study conducted per EPA Test Guidelines Series 860 on dry peas in which no residues were detected above the lowest level of method validation (0.0 2 ppm) in any of the tested agricultural c ommodities was submitted with this petition . The data from the previously submitted studies in conjunction with the data from the accompanying study on dry peas supports the proposed establishment of a tolerance of 0.05 ppm for the succulent and dried leg umes (Crop Group 6). A magnitude of the residue studies supporting the proposed tolerances of 0.02 ppm for the low
- growing berries (Crop Group 13 07G except cranberries) was submitted with this petition . This study was conducted per EPA Test Guidelines Se ries 860. No residues were detected above the lowest level of method validation (0.02 ppm) in any of the tested agricultural commodities. In this notice of filing, IR
- 4 further proposes that a tolerance for tuber and corm vegetables (Crop Group 1C) at 0 .025 parts per million be established based on the previously established potato tolerance of 0.0 2 5 ppm [EPA
- HQ
- OPP
- 2010
- 0122; FRL
8858
- 5] . Potatoes are the representative crop required for Crop Group 1C. B. Toxicological Profile The United States Environmental Protection Agency (EPA) has evaluated the available fomesafen toxicological database and considered its validity, completeness, and reliability as well as the relationship of the results of the studies to human risk. EPA has also considered available information concerning the reliability of the sensitivities of major identifiable subgroups of consumers, including infants and children. The nature of the toxicity profile of fomesafen is discussed in the March 9 , 20 11 Federal R egister publication of the Final Rule for establishing tolerances for residues of fomesafen in or on peppers (bell and non
- bell) , potatoes and tomatoes [EPA
- HQ
- OPP
- 2010
- 0122; FRL
8858
- 5] . 1. Acute toxicity. [NA
- Remove] 2. Genotoxicty. [NA
- Remove] 3. Reproductive and developmental toxicity. [NA
- Remove] 4. Subchronic toxicity. [NA
- Remove] 5. Chronic toxicity. [NA
- Remove] 6. Animal metabolism. [NA
- Remove]3
7. Metabolite toxicology . [NA
- Remove] 8. Endocrine disruption . [NA
- Remove] C. Aggregate Exposure 1. Dietary exposure. Tier I aggregate acute, short
- term, and chronic exposure assessments were performed for fomesafen using the Dietary Exposure Evaluation Model (DEEM
- FCIDTM, version 3.14) from Durango Software. These exposure assessments included all currently registered uses plus proposed new IR
- 4 uses on tuber and corm vegetables (Crop Group 1C), low
- growing berries (Crop Group 13 07G except cranberries), and succulent and dried legumes (Crop Group 6). Tolerance values were used for all raw agricultural commodities; no adjustments were made for percent crop treated (%CT). Because transfer factors as determined from goat and hen metabolism studies were very low, there is no expectation of residues in livestock commodities. D rinking water estimates were incorporated directly into the dietary exposure assessment using the higher of the estimated drinking water concentrations (EDWCs) for surface and/or ground water. i. Food. Acute Exposure. The fomesafen acute dietary risk assessment was performed for all population subgroups with an acute reference dose of 1.0 mg/kg
bw/day based on a neurotoxicity in rat with a no observed adverse effect level (NOAEL) of 100 mg/kg
- bw/day and an uncertainty factor of 100X. The 100X safety f actor includes intra
- and inter
- species variations. No additional FQPA safety factor was applied. For the purpose of aggregate risk assessment, the exposure values were expressed in terms of margin of exposure (MOE), which was calculated by dividing the NOAEL by the exposure for each population subgroup. In addition, exposure was expressed as a percent of the acute reference dose (%aRfD). Acute dietary (food only) exposure to the U.S. population resulted in a MOE of 308,031, or <0.1% of the aRfD (Benchm ark MOE = 100; aRfD = 1.0 mg/kg
- bw/day). The most exposed sub
- population was children 1
- 2 years old, with a MOE of 129,393 or 0.1% of the aRfD, (Benchmark MOE = 100; aRfD = 1.0 mg/kg
- bw/day). Chronic Exposure. The fomesafen chronic dietary risk assess ment was performed for all population subgroups with a chronic reference dose of 0.0025 mg/kg
- bw/day based on a chronic toxicity study in rats with a no observed adverse effect level (NOAEL) of 0.25 mg/kg
- bw/day and an uncertainty factor of 100X. The 100X safety factor includes intra
and inter
- species variations. No additional FQPA safety factor was applied. For the purpose of aggregate risk assessment, the exposure values were expressed in terms of margin of exposure (MOE), which was calculated by divi ding the NOAEL by the exposure for each population subgroup. In addition, exposure was expressed as a percent of the reference dose (%RfD). Chronic dietary (food only) exposure to the U.S. population resulted in a MOE of 2,214, or 4.5% of the chronic RfD (Benchmark MOE = 100; cRfD = 0.0025 mg/kg
- bw/day). The most exposed sub
- population was children 1
- 2 years old, with a MOE of 837 or 11.9% of the cRfD, (Benchmark MOE = 100; cRfD =4

0.0025 mg/kg
- bw/day). Cancer . Fomesafen has been classified as not lik ely to be carcinogenic in humans, so cancer risk assessments were not performed. ii. Drinking water . The Estimated Drinking Water Concentrations (EDWCs) of fomesafen were determined for groundwater using results from a 3
- year prospective groundwater (PGW ) study and for surface water using the Tier II Surface Water Concentration Calculator model (v. 1.106). The currently registered uses and proposed uses on low growing berries (crop group 13
- 07 excluding cranberry), tuberous and corm vegetables (crop subgr oup 1C), and legume vegetables (succulent or dried, crop group 6) were assessed. For ground water, the PGW monitoring concentration for fomesafen was 1.0 ppb (chronic). For surface water, the currently registered use on soybeans and the proposed use for ot her crops in group 6 produced the highest acute EDWC of 44.41 ppb, and the highest chronic EDWC of 7.36 ppb, (adjusted for 0.91 Percent Cropped Area). Because the surface water EDWCs (44.41 ppb for acute, 7.36 ppb for chronic) exceed the groundwater EDWC ( 1.0 ppb), the surface water values are used for risk assessment purposes and are considered protective for any groundwater concentration concerns. The acute surface water EDWC of 44.41 ppb was used in DEEM
- FCIDTM model to estimate acute exposures from drinking water. Acute drinking water exposure to the U.S. population resulted in an acute drinking water MOE of 43,879 (0.2% of the aRfD of 1.0 mg/kg
- bw/day). The most sensitive sub
- population was all infants <1 year old, with an acute drinking water MOE of 13,904 (0.7% of the aRfD of 1.0 mg/kg
- bw/day). Chronic Exposure from Drinking Water : The chronic surface water EDWC of 7.36 ppb was used as in the DEEM
- FCID model to estimate chronic exposures from drinking water. Chronic drinking water exposure t o the U.S. population resulted in a chronic drinking water MOE of 1,613 (6.2% of the cRfD of 0.0025 mg/kg
- bw/day). The most sensitive sub
- population was all infants <1 year old, with a chronic drinking water MOE of 626 (16.0% of the cRfD of 0.0025 mg/kg
- b w/day). 2. Non
- dietary exposure . There are no current or proposed residential uses of fomesafen that would result in residential exposures. However, there is the potential for exposure to adults, youths, and children due to off
- site drift of agricult ural products onto residential areas. Scenarios assessed included child and adult high contact lawn, adult and youth mower, adult and youth golfer, child hand
- to - mouth, child object
- to - mouth, and child soil ingestion. The highest relevant exposures for a ll subpopulations via all residential activities was an MOE of 6,986 for adults 19+ (adult high contact lawn), 151,167 for youths 11
- 16 (youth golf), and 3,838 for children 1
- 6 years (child hand
- to mouth), with a Level of Concern = 100. According to recen t EPA guidance, in the absence of a transferable turf residue study, an MOE of 10x the LOC is needed to waive the requirement for a TTR study; the MOEs for hand
- to - mouth exposure are greater than 10x the LOC and therefore a TTR study is not required.5

D. Cumulative Effects Cumulative Exposure to Substances with a Common Mechanism of Toxicity. Section 408(b)(2)(D)(v) requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider “available information” concerning the cumulative effects of a particular pesticide’s residues and “other substances that have a common mechanism of toxicity”. The EPA does not have, at this time, available data to determine whether fomesafen has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment. For the purposes of this tolerance action, the EPA has not assumed that fomesafen has a common mechanism of toxicity with other substances. E. Safety Determination 1. U.S. population. The acute dietary exposure analysis (food plus water) showed that exposure from all current and proposed uses of fomesafen would result in a MOE of 38,400 (0.3% of the aRfD) for the general U.S. population. The short
- term aggregate analysis (f

ood plus water plus residential) showed that exposure from all current and proposed uses of fomesafen would result in a MOE of 9,499 for the general U.S. population. The chronic dietary exposure analysis (food plus water) showed that exposure from all cur rent and proposed uses of fomesafen would result in a MOE of 933 (10.7% of the cRfD) for the general U.S. population. 2. Infants and children . The acute dietary exposure analysis (food plus water) showed that exposure from all current and proposed uses of fomesafen would result in a MOE of 12,810 (0.8% of the aRfD) for infants <1 year old. The short
- term aggregate analysis (food plus water plus residential) showed that exposure from all current and proposed uses of fomesafen would result in a MOE of 3,307 for children 1
- 2 years old. The chronic dietary exposure analysis (food plus water) showed that exposure from all current and proposed uses of fomesafen would result in a MOE of 419 (23.9% of the cRfD) for infants <1 year old. F. International Tolerances There are no Codex maximum residue levels (MRLs) established for residues of fomesafen in any commodity.