EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER EPA Registration Division contact: [ Bethany Benbow (703) 347 - 8072 ]

FMC Corporatio n, 1735 Market Street, Philadelphia, PA 19103 [ 1F7839 ] EPA has received a pesticide petition ( 1F7839) from FMC Corporation , 1735 Market street, Philadelphia, PA 19103 , 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 p art 180. 515 by

establishing a tolerance for residues o f carfentrazone - eth yl (ethyl - - 2 - dichloro - 5 - [4 - (difluoromethyl) - 4,5 - dihydro - 3 - methyl - 5 - oxo - 1H - 1,2,4 - triazol - 1 - yl ] - 4 - fluorobenzene - propanoate) and the metabolite carfentrazone - eth yl chloropropionic acid ( α , 2 - dichloro - 5 - [4 - (difluoromethyl) - 4,5 - dihydro - 3 - methyl - 5 - oxo - 1H - 1,2,4 - triazol - 1 - yl ] - 4 - fluorobenzenepropanoic acid) ] in or on the raw agricultural commodity [ Crop Group 18 Non - grass animal feed (forage, fodder, straw and hay): alfalfa , forage at 5 ppm; a lfalfa, hay

at 18 ppm; alfalfa, seed at 10 ppm; clover , forage at 5 ppm; clover , hay at 18 ppm; clover , seed at 10 ppm parts per million (ppm). EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of the 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. [The metabolism of carfentrazone - eth yl in plants is adequatel y understood. Corn, wheat, radish and soy bean metabolism studies with carfentrazone - eth yl have shown uptake of material into plant tissue with no significant movement into grain, root or seeds. All four plants extensively metabolized carfentrazone - eth yl and exhibited a similar metabolic pathway . The residues of concern are the combined residues of carfentrazone - eth yl and carfentrazone - eth yl chloropropionic a cid. 2. Analytical method. There is a practical anal yt ical method for detecting and measuring levels of carfentrazone - eth yl and its metabolite in or on food with a limit of quantitation that allows monitoring of food with residues at or above the level s set or proposed in the tolerances. The anal yt ical enforcement method for carfentrazone - eth yl was used with minor modification that eliminated several clean - up and derivatization steps that was required for GC/MSD but not for LC/MS/MS. The analytical me thod for carfentrazone - eth yl involves separate analy se s for parent and its metabolite . The parent is analyzed by

evaporation and reconstitution of the sample prior to analy sis by L C/MS/MS GC/ECD. The metabolite samples were refluxed in the presence of ac id and cleaned up with solid phase extraction prior to analysis b y LC /MS/MS. 3. Magnitude of residues. The magnitude of the residue of carfentrazone - ethyl and its major metabolites in/on Crop Group 18 (non - grass animal feed) representative crops alfalf a and clover treated with Spartan Charge Herbicide were determined. Forage/hay plots were treated with one or two applications of carfentrazone - eth yl for a cumulative application of 0.04 lbs ai/A. Applications to each treated plot in this study were made using a spray

solution of approximately 10 GPA. Each field trial followed one of three treatment ty

pes: single dormant application, single stubble application or split dormant and stubble applications. Seed plots were treated with one application of carfentrazone ethyl at a rate of 0.04 lbs ai/A. At maturity , seed plots were treated with carfentrazone ethyl at a rate of 0.06 lbs ai/A as a harvest aid for seed samples. RAC for each crop were harvested at the appropriate time and subsequent anal ys es determine d that the residues of carfentrazone - eth yl and its metabolites would not exceed the proposed tolerances. B. Toxicological Profile 1. Acute toxicity. Carfentrazone - eth yl demonstrates low oral, dermal and inhalation toxicity . The acute oral LD 50 valu e in the rat was greater than 5000 mg/kg, the acute dermal LD 50 value in the rat was greater than 4000 mg/kg and the acute inhalation LC 50 value in the rat was greater than 5.09 mg/L/4h. Carfentrazone - eth yl is non - irritating to rabbit skin and minimally i rritating to rabbit eyes. It did not cause skin sensitization in guinea pigs. An acute neurotoxicity study in the rat had a s ys temic NOAEL of 500 mg/kg based on clinical signs and decreased motor activity levels; the NOAELfor neurotoxicity

was greater than 2000 mg/kg (highest dose tested) based on the lack of neurotoxic clinical signs or effects on neuropathology .2. Genotoxicty. Carfentrazone - ethyl did not cause mutations in the Ames assay

with or without metabolic activation. There was a positive response in the Chromosome Aberration assay

without activation but a negative response with activation. The Mouse Micronucleus assay

(an in vivo test which also measures chromosome damage), the CHO/HGPRT forward mutation assay and the Unscheduled DNA Sy nthesis assay

were negative. The overwhelming weight of the evidence supports the conclusion that Carfentrazone - eth yl is not genotoxic. 3. Reproductive and developmental toxicity. Carfentrazone - eth yl is not considered to be a reproductive or a developme ntal toxin. In the 2 - generation reproduction study , the NOEL for reproductive toxicity was greater than 4000 ppm (greater than 323 to greater than 409 mg/kg/day). In the developmental toxicity studies, the rat and rabbit maternal NOELs were 100 mg/kg/day and 150 mg/kg/day , respectivel y. The developmental NOEL for the rabbit was greater than 300 mg/kg/day , which were the highest dose tested and for the rat the NOEL was 600 mg/kg/day based on increased litter incidences of thickened and wavy ribs at 1250 m g/kg/day . These two findings (thickened and wav y ribs) are not considered adverse effects of treatment but related delay s in rib development which are generall y believed to be reversible. 4. Subchronic toxicity. Ninety - day feeding studies were conduct ed in mice, rats and dogs with Carfentrazone - eth yl . The NOEL for the mouse study was 4000 ppm (571 mg/kg/day), for the rat study was 1000 ppm (57.9 mg/kg/day for males; 72.4 mg/kg/day for females) and for dogs was 150 mg/kg/day . A 90 - day subchronic neuro toxicity study in the rat had a s ys temic NOEL of 1000 ppm (59.0 mg/kg/day for males; 70.7 mg/kg/day for females) based on decreases in bod y weights, body weight gains and food consumption at 10,000 ppm; the neurotoxicity NOELwas greater than 20,000 ppm (1 178.3 mg/kg/day

for males; 1433.5 mg/kg/day for females) which was the highest dose tested. 5. Chronic toxicity. Carfentrazone - eth yl is not carcinogenic to rats or mice. A 2 - Year Combined Chronic Toxicity /Oncogenicity

study in the rat was negative for carcinogenicity

and had a chronic toxicity NOEL of 200 ppm (9 mg/kg/day) for males and 50 ppm (3 mg/kg/day) for females based on red fluorescent granules consistent with porphy rin deposits in the liver at the 500 and 200 ppm levels, respectivel y. An 18 M onth Oncogenicit y study in the mouse had a carcinogenic NOEL that was greater than 7000 ppm (>1090 mg/kg/day

for males; >1296 mg/kg/day for females) based on no evidence of carcinogenicit y at the highest dose tested. A 1 - Year Oral Toxicity study in the do g had a NOEL of 50 mg/kg/day based on isolated increases in urine porphy rins in the 150 mg/kg/day

group (this finding was not considered adverse). Using the Guidelines for Carcinogen Risk Assessment, carfentrazone - ethyl should be classified as Group A E @ fo r carcinogenicit y -- no evidence of carcinogenicity -- based on the results of carcinogenicity studies in two species. There was no evidence of carcinogenicity

in an 18 - month feeding stud y in mice and a 2 - ye ar feeding stud y in rats at the dosage levels t ested. The doses tested are adequate for identifying a cancer risk. Thus, a cancer risk assessment is not necessary.6. Animal metabolism. The metabolism of carfentrazone - eth yl in animals is

adequatel y understood. Carfentrazone - eth yl was extensively metabolized and readil y eliminated following oral administration to rats, goats, and poultry via excreta. All three animals exhibited a similar metabolic pathway . As in plants, the parent chemical was metabolized by

hydrol yt ic mechanisms to predominantly form carfentrazone - eth yl chloropropionic acid, which was readily excreted. 7. Metabolite toxicology . [ NA ] 8. Endocrine disruption . An evaluation of the potential effects on the endocrine sy stems of mammals has not been determined; however, no evi dence of such effects was reported in the chronic or reproductive toxicology studies described above. There was no observed pathology

of the endocrine organs in these studies. There is no evidence at this time that carfentrazone - ethyl causes endocrine ef fect. C. Aggregate Exposure 1. Dietary exposure. Based on the available toxicity data, the EPA has established a Reference Dose (R f

D) and cPAD for carfentrazone - eth yl of 0.03 mg/kg/day . This is based on a 2 - ye ar chronic toxicity /carcinogenicity stu dy

in rats with a threshold No Observed Effect Level (NOEL) of 3 mg/kg/day and an uncertainty

factor of 100. In support of the proposed harvest - aid application the Agency conducted acute and chronic dietary risk assessments. For both analy sis 100% crop - treated, default processing factors and modeled drinking water estimates resulting from the highest registered proposed application rate of 0.4 lbs ai/acre, tolerance - level residues for livestock, fish, shellfish, cereal grains and cotton commodities were made. Using the above assumptions, the resulting acute and chronic exposure estimates were aPAD <1% and cPAD <89% respectivel y. i. Food. Dietary

exposure from the proposed harvest - aid application accounts for 1.0% or less of the aPAD in subpopulations (including infants and children). Dietary exposure from all uses would accounts for 89% or less of the cPAD in subpopulations (including infants and children). ii. Drinking water. Ground water estimate of 13.4 ppb, surface water estimates of 34.3 ppb (peak concentration) and 19.0 ppb (annual average) were incorporated directly into the a cute and chronic dietary assessment by

the Agency . 2. Non - dietary exposure . Non - occupational exposures to carfentrazone - ethyl are anticipated from the lawn, turf and aquatic applications. The resulting MOEs were calculated to be >500,000. D. Cumulative Effects EPA is also required to consider the potential for cumulative effects of carfentrazone - eth yl and other substances that have a co mmon mechanism of toxicity .EPA consideration of a common mechanism of toxicity is not appropriate at this time since EPA does not have information to indicate that toxic effects produced by carfentrazone - eth yl would be cumulative with those of an y other chemical compounds; thus only the potential risks of carfentrazone - eth yl are considered in this exposure assessment. E. Safety Determination 1. U.S. population. Using the conservative exposure assumptions described and based on the completeness and reliability of the toxicity

data, the aggregate exposure to carfentrazone - eth yl will utilize less than 1% of the aPAD and less than 32% of the cPAD for the US subpopulations. EPA generall y has no concern for exposures below 100 percent of the aPAD or cPAD . Therefore, based on the completeness and reliability of the toxicity

data and the conservative exposure assessment, there is a reasonable certainty that no harm will result from aggregate exposure to residues of carfentrazone - eth yl , including all antici pated dietary exposure and all other non - occupational exposures. 2. Infants and children . In assessing the potential for additional sensitivity of infants and children to residues of carfentrazone - ethyl, EPA considers data from developmental toxicity

s tudies in the rat and rabbit and the two - generation reproduction study in the rat. The developmental toxicity studies are designed to evaluate adverse effects on the developing organism resulting from pesticide exposure during prenatal development. Repro duction studies provide information relating to effects on the reproductive capacity

of males and females exposed to the pesticide. Developmental toxicity was not observed in developmental toxicity studies using rats and rabbits. In these studies, the rat and rabbit maternal NOELs were 100 mg/kg/day and 150 mg/kg/day , respectivel y. The developmental NOELfor the rabbit was greater than 300 mg/kg/day , which was the highest dose, tested and for the rat was 600 mg/kg/day based on increased litter incidences of thickened and wavy ribs. These two findings are not considered adverse effects of treatment but related delay s in rib development, which are generall y believed to be reversible. In a two - generation reproduction study in rats, no reproductive toxicity was observed under the conditions of the study at 4000 ppm, which was the highest dose tested. FFDCA section 408 provides that EPA may apply an additional safet y factor for infants and children in the case of threshold effects to account for pre - and pos t - 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 and an additional uncertaint y factor is not warranted. Therefore at this time, the R f D of 0.03 mg/kg/day

is appropriate for assessing aggregate risk to infants and children. Population Adjusted Dose (aPAD and cPAD) Using the conservative exposure assumptions described above, the percent of the aPAD that will be utilize d by

aggregate exposure to residues of carfentrazone - eth yl for non -nursing infants (<1 ye ar old) would be < 1% (aPAD) and < 53% (cPAD); for children 1 - 6

ye ars of age would be < 1% (aPAD) and < 89% (cPAD), (the most highly exposed group). Based on the comp leteness and reliability of the toxicity

data and the conservative exposure assessment, there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the residues of carfentrazone - eth yl including all anticipate d dietary exposure. F. International Tolerances Canadian MRL s are established for root and tuber vegetables (Crop Group 1), bulb vegetables (Crop Group 3), leafy vegetables (Crop Groups 4 and 5), legume vegetables (Crop Group 6), fruiting vegetables (Crop Group 8), cucurbit vegetables (Crop Group 9), pome fruits (Crop Group 11), stone fruits (Crop Group 12), berries (Crop Group 13), cereal grains (Crop Group 15), oilseeds (Crop Group 20), grapes and strawberries. There are no established Codex Alimentarius Commission (Codex) Maximum Residue L evels (MRL s) for carfentrazone - eth yl , in/on the proposed commodities.