


EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Laura Nollen, (703) 305-7390



Interregional Research Project Number 4 (IR-4) 

Petition Number (PP#) 2E8061

EPA has received a pesticide petition, PP# 2E8061, from Interregional Research Project Number 4 (IR-4), 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 180.433 by establishing a tolerance for residues of sodium salt of fomesafen (fomesafen), 5-[2-chloro-4-(trifluoromethyl)phenoxy]-N-(methylsulfonyl)-2-nitrobenzamide in or on the raw agricultural commodities cantaloupe; cucumber; pea, succulent; pumpkin; squash, summer; squash, winter; and watermelon at 0.025 parts per million (ppm)  and vegetable, soybean, succulent (edamame) 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 [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 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 analyzed by GC-NPD. The limit of quantitation is 0.025 ppm.

	3. Magnitude of residues. Magnitude of the residue studies supporting the proposed tolerances in or on these raw agricultural commodities (cantaloupe; cucumber; pea, succulent; pumpkin; summer squash; watermelon and winter squash) were submitted with this petition.  These studies were conducted per EPA Test Guidelines Series 860.  No residues were detected above the lowest level of method validation (0.025 ppm) in any of the tested agricultural commodities.  

A tolerance for vegetable, soybean, succulent (edamame) of 0.05 ppm is also proposed based on the previously established snap bean tolerance.


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; 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]

	7. Metabolite toxicology.  [NA-Remove]

	8. Endocrine disruption.  [NA-Remove]


C. Aggregate Exposure

	1. Dietary exposure. A Tier I chronic dietary exposure evaluation was performed for fomesafen using the Dietary Exposure Evaluation Model (DEEM-FCIDTM, version 2.16) from Exponent.  These exposure assessments included all currently registered uses for current fomesafen uses including dry beans, succulent snap beans, cotton, soybeans, potatoes, tomatoes, peppers, and proposed uses on cucurbit vegetables (Crop Group 9), succulent shelled and podded peas, and edamame (vegetable, soybean, succulent).  Tolerance values were used for all raw agricultural commodities; no adjustments were made for percent crop treated (%CT).  There are no expected dietary exposures as a result of residues of fomesafen in meat, milk, or eggs based upon low levels of residues in feedstuffs and low transfer factors as determined from the goat and hen metabolism studies.  Drinking water estimates were incorporated directly into the dietary exposure assessment using the higher of the estimated drinking water concentrations (EDWCs) for surface and ground water.

	i. Food. Acute Exposure.  Acute toxicological endpoints have not been established, so acute food assessments were not performed.

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 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 reference dose (%RfD).  Chronic dietary (food only) exposure to the U.S. population resulted in a MOE of 2,089, or 4.8% 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 884, or 11.3% of the chronic RfD, (Benchmark MOE = 100; cRfD = 0.0025 mg/kg-bw/day).  Since the Benchmark MOE for this assessment was 100 and since the EPA generally has no concern for exposures above the benchmark or below 100% of the reference dose, Syngenta believes that there is a reasonable certainty that no harm will result from chronic dietary (food only) exposures to residues arising from all current and proposed uses for fomesafen.

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 PRZM/EXAMS model which estimates pesticide concentrations in surface water.  The currently registered uses plus proposed uses on peas (succulent), cucumbers, squash, pumpkins, cantaloupes, watermelon, and edamame (vegetable, soybean, succulent) were assessed.   For ground water, the PGW monitoring concentration for fomesafen was 1 ppb (chronic).  For surface water, the currently registered use on soybeans as well as the proposed use on edamame provided the highest chronic EDWC of 7.617 ppb (adjusted for 0.91 Percent Cropped Area, PCA).  Since the surface water chronic EDWC exceeds the ground water EDWC, the surface water value was used for risk assessment purposes and will be considered protective for any ground water exposure concerns.  

Chronic Exposure from Drinking Water:  The chronic EDWC of 7.617 ppb was input directly into the DEEM-FCID(TM) software as "water, direct and indirect, all sources" to model the chronic drinking water exposure.   Chronic drinking water exposure to the U.S. population resulted in a MOE of 1,557 or 6.4% of the cRfD (Benchmark MOE = 100; cRfD = 0.0025 mg/kg-bw/day).  The most sensitive sub-population was all infants (<1 year old), with a MOE of 475 or 21.1% of the cRfD (Benchmark MOE = 100; cRfD = 0.0025 mg/kg-bw/day).  Since the Benchmark MOE for this assessment was 100 and since the EPA generally has no concern for exposures above the benchmark or below 100% of the reference dose, Syngenta believes that there is a reasonable certainty that no harm will result from chronic drinking water exposures to residues arising from all current and proposed uses for fomesafen.


	2. Non-dietary exposure. There are no current or proposed uses of fomesafen that would result in residential exposures.

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 chronic dietary exposure analysis (food plus water) showed that exposure from all current, pending, and proposed uses of fomesafen would result in a MOE of 892 (11.2% of the chronic RfD) for the general U.S. population.  Since the Benchmark MOE for this assessment was 100 and since the EPA generally has no concern for exposures above the benchmark, Syngenta believes that there is a reasonable certainty that no harm will result to the U.S. population from chronic aggregate exposures to residues arising from all current and proposed uses for fomesafen.

	2. Infants and children. The chronic dietary exposure analysis (food plus water) showed that exposure from all current, pending, and proposed uses of fomesafen would result in a MOE of 366 (27.3% of the chronic RfD) for infants <1 year old.  Since the Benchmark MOE for this assessment was 100 and since the EPA generally has no concern for exposures above the benchmark, Syngenta believes that there is a reasonable certainty that no harm will result to infants or children from chronic aggregate exposures to residues arising from all current and proposed uses for fomesafen.

F. International Tolerances

There are no Codex maximum residue levels (MRLs) established for residues of fomesafen in any commodity.  A Canadian tolerance of 0.05 ppm is established for fomesafen residues in or on soybeans, dry beans, lima beans, and snap beans.  A Mexican tolerance of 0.01 ppm is established for fomesafen residues in or on beans.
