EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

Interregional Research Project Number 4 (IR-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 tolerances for residues of fomesafen, 5-[2-cloro-4-

(trifluoromethyl)phenoxy]-N-(methylsulfonyl)-2-nitrobenzamide in or on the raw 

agricultural commodities 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 ppm; 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 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. Cotton, soybean and tomato metabolism studies were 

conducted using 14C-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 fomesafen. 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 chromatography 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 acidified 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 potassium carbonate. A silica gel column cleanup is done, with 

dichloromethane:hexane as the eluent. The final extract is transferred to toluene and 
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analyzed by GC-NPD. The limit of quantitation is 0.025 ppm.

3. Magnitude of residues. Magnitude 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 (0.02 ppm) in any of the tested agricultural commodities 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 legumes 

(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 Series 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 0.025 ppm [EPA-HQ-OPP-2010-0122; FRL8858-5]. 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, 2011 Federal Register 

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; FRL8858-5]. 

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]
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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. 

Drinking 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/kgbw/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 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 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 

(Benchmark 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 assessment 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 intraand 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 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 = 
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0.0025 mg/kg-bw/day). 

Cancer. Fomesafen has been classified as not likely 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 subgroup 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 other 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 to 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-bw/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 agricultural 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 all 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-tomouth), with a Level of Concern = 100. According to recent 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. 
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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 (food 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 current 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.