b y establishing a tolerance for residues of Sulfentrazone

(N

- [2,4

- dichloro

- 5

- [4

- (difluoromethyl)

- 4,5

- dihy dro

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- methy l

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- oxo - 1H

- 1,2,4

- triazol

- 1

- yl ]phe ny l]

- methanesulfonamide) and its metabolites 3

- hy droxy

methy l

- sulfentrazone(N

- [2,4

- dichloro

- 5

- [4

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- 4,5

- dihy dro

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- hy droxy methy l

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- 1,2,4

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- yl ]pheny l]methanesulfonamide) and 3

- desmethyl sulfentrazone(N

- [2,4

- dichloro

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- y l]pheny l]methanesulfonamide)] in or on the raw agricultural commodity [Citrus Fruit Crop Group 10

- 10; Berry and Small Fruit Crop Group 13

- 07; Tree Nut Crop Group 14 and Pistachio at 0.15 parts per million (ppm); Crop Group 18 Non

- grass animal feed (forage, fodder, straw and hay) : alfalfa, forage at 5 ppm; alfalfa , hay at 20 ppm; alfalfa, seed at 3 ppm; clover, forage at 5 ppm; clover, hay at 20 ppm; clover, seed at 3 ppm. E PA has determined that the petition contains data or information regarding the elements set forth in section 408 (d) (2) of FDDCA; however, EP A 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. EPA REGISTRATION DIVISION COMPANY NOTICE O F FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER EPA Registration Division contact: Bethany Benbow (703) 347 - 8072

FMC Corporation, 1735 Market Street, Philadelphia, PA 19103 [1F7838] EPA has received a pesticide petition (1F7838) 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 part 180.498A. Residue Chemistry

1. Plant metabolism. The metabolism of sulfentrazone in plants is adequately understood fo r the existing and proposed tolerances. Crop residues found after the pre - emergence and the proposed post - emergence uses were similar in that the major metabolites were 3 - hydroxymethyl sulfentrazone and 3 - desmethyl sulfentrazone. In rotational crops, sulfentrazone is metabolized via four different pathways: (i) Oxidation of the 3 - methyl group to form 3 - hydroxymethyl sulfentrazone, followed by further oxidation to form sulfentrazone carboxylic acid which is decarboxylated to 3 - desmethyl sulfentrazone; (ii) hydrolysis of the trifluoromethyl group to form desdif luoromethyl sulfentrazone which is oxidized and decarboxylated to form desdifluoromethyl desmethyl sulfentrazone; (iii) hydrolysis of the sulfonamide group to form desmethylsulfonyl sulfentrazone; and (iv) scission of the phenyl and triazole rings to produ ce methyl triazole. The corresponding phenyl metabolites are believed to remain bound. EPA determined that tolerances based on the parent and 3 - hydroxymethyl sulfentrazone are therefore appropriate.

2. Analytical method. There is a practical analy tical method for detecting and measuring levels of sulfentrazone and its metabolites in or on food with a limit of quantitation that allows monitoring of food with residues at or above the levels set or proposed in the tolerances. T he analytical enforceme nt method for sulfentrazone was used with minor modification that eliminated several clean - up and derivatization steps that was required fo r GC/MSD but not for LC/MS/MS. T he analytical method for sulfentrazone involves separate analyses for parent and its metabolites. T he parent is analyzed by evaporation and reconstitution of the sample prior to analysis by LC/MS/MS GC/ECD. T he metabolites samples were refluxed in the presence of acid and cleaned up with solid phase extraction prior to analysis by LC/MS /MS.

3. Magnitude of residues. Sulfentrazone was applied at the maximum label rates for alfalfa, clover, citrus, tree nuts, berries and small fruit to trials in the appropriate EPA regions. T he RACs were harvested at the appropriate growth stages. The subsequent analyses of the RACs and processed parts determined that the residues of sulfentrazone and its metabolites would not exceed the established and proposed tolerances. B. Toxicological Profile 1. Acute toxicity. A battery of acu te toxicity studies placed technical sulfentrazone in Toxicity Categories III and IV. No evidence of sensitization was observed following dermal application in guinea pigs. In an acute neurotoxicity study in rats at gavage doses of 0, 750, or 2,000 mg/kg, a NOEL of 250 mg/kg and a LOEL of 750 mg/kg were based upon increased incidences of clinical signs, Functional Observation Battery (FOB) findings, and decreased motor activity which were reversed by day 14 post - dose. There was no evidence of neuropathology .2. Genotoxicity. A reverse gene mutation assay (salmonella typhimurium) yielded

negative results, both with and without metabolic activation. A mouse lymphoma fo rward gene mutation assay yielded negative results with equivocal results without activation. A mouse micronucleus assay test was negative following intraperitoneal injectio n of 340 mg/kg. 3. Reproductive and developmental toxicity. [A prenatal oral developmental toxicity study in the rat with dose levels at 25.0 or 50.0 mg/kg/day established a maternal NOEL of 25 mg/kg/day based on decreased body weight gain, incre ased spleen weight, and microscopic changes in the spleen, and a fetal NOEL of 10 mg/kg/day was based on fetal death, reduced body weights, and alterations in skeletal development at higher doses. A supplemental oral developmental toxicity study conducted in rats at oral dose levels of 25.0 and 50.0 mg/kg/day to test for cardiac effects at the request of the EPA, did not reveal any significant effects on fetal cardiac development. The results of this study confirmed the maternal and fetal findings of the p reviously conducted developmental study on sulfentrazone in rats and did not alter the study conclusions. In a dermal developmental study in the rat at doses of 0, 5, 25, 50, 100 and 250 mg/kg/day, a maternal (systemic) No Observed Adverse Effect Le vel (NOAEL) was established at 250 mg/kg/day. Significant treatment - related increases in the fetal and litter incidences of incompletely ossified lumbar vertebral arches, hypoplastic or wavy ribs, and incompletely ossified or nonossified ischia or pubes oc curred at the high - dose (250 mg/kg/day). An additional significant increase in the high - dose fetal incidence of variations in the sternebrae (incompletely ossified or unossified) was not judged to be treatment - related. At 250 mg/kg/day, the mean numbers of thoracic vertebral and rib ossification sites were significantly decreased, a high - dose effect of treatment with sulfentrazone consistent with the significant treatment - related hypoplasia observed in the skeletal evaluation of the ribs. Therefore, the dev elopmental (fetal) Lowest Observed Effect Level (LOEL) is 250 mg/kg/day based on decreased fetal body weight; increased incidences of fetal variations: hypoplastic or wavy ribs, incompletely ossified lumbar vertebral arches, and incompletely ossified ischi a or pubes; and reduced number of thoracic vertebral and rib ossification sites. The developmental (fetal) NOEL is 100 mg/kg/day. A developmental toxicity study in rabbits was conducted at gavage dose levels of 0, 100, 250, or 375 mg/kg/day. Treatme nt - related incidences of decreased feces and hematuria were noted at 250 mg/kg/day or greater. In addition, at the 375 mg/kg/day dose level, five rabbits aborted. Significant reductions in mean body weight change were observed for the dosing period (GD 7 - 19) and for the study duration (GD 0 - 29, both before and after adjustment for gravid uterine weight) at the 250 and 375 mg/kg/day dose levels. Therefore, the maternal (systemic) LOEL is 250 mg/kg/day, based upon increased abortions, clinical signs (hematur ia and decreased feces), and reduced body weight gain. The maternal (systemic) NOEL is 100 mg/kg/day. Skeletal evaluation in fetuses revealed dose - and treatment - related findings at the 375 mg/kg/day dose level. These included significant increases in both the fetal and litter incidences of fused caudal vertebrae (a malformation) and of partially fused nasal bones (a variation). In addition, at 375 mg/kg/day, significant treatment - related reductions in ossification site averages were observed for metacarpal s and both fore - and hindpaw phalanges. Therefore, the developmental (fetal) LOEL is 250 mg/kg/day, based upon increased resorptions, decreased live fetuses per litter, and decreased fetal weight. The developmental (fetal) NOEL is 100 mg/kg/day.A two - generation reproduction study in the rat at dietary levels of 14, 33, or 46 mg/kg/day

in males and 16, 40, or 56 mg/kg/day in females established a NOEL for systemic and reproductive/developmental parameters of 14 mg/kg/day for males and 16 mg/kg/day for f emales. The LOEL for systemic and reproductive/development parameters was 33 mg/kg/day for males and 40 mg/kg/day for females. Systemic effects were comprised of decreased body weight gains, while reproductive/developmental effect at the LOEL included dege neration and/or atrophy in the testes, with epididymal sperm deficits, in the second (F1) generation males. Male fertility in the F1 generation was reduced at higher doses; litter size, pup survival, and pup body weight for both generations were also effec ted at higher doses. A supplemental two - generation rat reproduction study was conducted at dietary intake levels of 50, 100, 200, or 500 ppm with a NOEL for reproductive parameters of 200 ppm. This study confirmed the reproductive/developmental effects observed in the first two - generation reproductive toxicity study. It was the conclusion of the RfD/Peer Review Committee that, under the conditions of the studies reviewed, sulfentrazone caus ed developmental and reproductive toxicity. The results of these studies elicited a high level of concern by the Committee, since the developmental toxicity studies demonstrated embryo/fetal toxicity at treatment levels that were not maternally toxic, and significant toxic effects were observed primarily in the second generation animals of the reproduction study. Because these animals had been exposed to sulfentrazone in utero, the possibility that the observed reproductive toxicity resulted from a developm ental and/or genotoxic mechanism was suggested.

4. Subchronic toxicity. A 90 - day subchronic toxicity study was conducted in rats, with dietary intake levels of 0, 3.3, 6.7, 19.9, 65.8, 199.3, or 534.9 mg/kg/day for males and 0, 4, 7.7, 23.1, 78.1, 230.5, or 404.3 milligrams/kilograms/day (mg/kg/day) for females respectively. No Observed Effect Levels (NOELs) of 19.9 mg/kg/day in males and 23.1 mg/kg/day in females were based on clinical anemia. A 90 - day subchronic feeding study was conducte d in mice by dietary admix at doses of 0, 10.3, 17.8, 60.0, 108.4, or 194.4 mg/kg/day for males and 0, 13.9, 29.0, 79.8, 143.6, or 257.0 mg/kg/day for females, respectively. NOELs of 60 mg/kg/day (males) and 79.8 mg/kg/day (females) were based on decreases in body weights and/or gains; decreased erythrocytes, hemoglobin and hematocrit values; and splenic microscopic pathology.In a 90 - day subchronic feeding study in dogs administered by dietary admix at doses of

0, 10, 28, or 57 mg/kg/day for male s and 0, 10, 28, or 73 mg/kg/day for females, a NOEL of 28 mg/kg/day was determined for both males and females based on decreases in hemoglobin and hematocrit, elevated alkaline phosphatase levels, increased liver weights and microscopic liver as well as s plenic changes. A 90 - day subchronic neurotoxicity study in the rat was conducted at dietary levels of 30, 150, or 265 mg/kg/day in males, and 37, 180, or 292 mg/kg/day in females, with a NOEL of 30 mg/kg/day in males and 37 mg/kg/day in females. The LOEL was 150 mg/kg/day fo r males and 180 mg/kg/day for females based on increased incidences of clinical signs, decreased body weights, body weight gains, and food consumption in females and increased motor activity in females at week 13. There were no ne urohistopathological effects on the peripheral or central nervous system. 5. Chronic toxicity. A 12 - month feeding study in dogs was dosed at levels of 0.0, 24.9, or 61.2 mg/kg/day for male dogs and 0.0, 10.4, 29.6, or 61.9 mg/kg/day for female dogs in the control through high - dose groups, respectively, with a NOEL of 24.9 mg/kg/day for males and 29.6 mg/kg/day for females based on hematology effects and microscopic liver changes. An 18 - month feeding/carcinogenicity study in mice wa s conducted with dietary intake of 0, 46.6, 93.9, 160.5, or 337.6 mg/kg/day for males and 0, 58.0, 116.9, 198.0, or 407.1 mg/kg/day for females. A NOEL of 93.9 mg/kg/day in males and 116.9 mg/kg/day in females was based on decreases in hemoglobin and hemat ocrit. There were no treatment - related increases in tumors of any kind observed at any dose level. In a 24 - month chronic feeding/oncogenicity study in rats at dietary doses of 0, 24.3, 40.0, 82.8, or 123.5 mg/kg/day for males and 20.0, 36.4, 67.0, o r 124.7 mg/kg/day for females, an overall NOEL of mg/kg/day in males and 36.4 mg/kg/day in females was based on hematology effects and reduced body weights. There was no evidence of an oncogenic response . 6. Animal metabolism. A metabolism study in rats indicated that approximately 84 to 104% of the orally administered dose of sulfentrazone was excreted in the urine, and that the pooled urinary radioactivity consisted almost entirely of 3 - hydroxymethyl sulfentrazone. Pooled fecal radioactivity showe d that the major metabolite consisted of 3 - hydroxymethyl - sulfentrazone (1.26 to 2.55% of the administered dose). The proposed metabolic pathway appeared to be conversion of the parent compound mainly to 3 - hydroxymethyl - sulfentrazone (excreted in urine and feces). 7. Metabolite toxicology. [NA]

8. Endocrine disruption

. An evaluation of the potential effects on the endocrine systems of mammals has not been determined; however, no evidence 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 sulfentrazone causes endocrine effects.C. Aggregate Exposure

1. Dietary exposure. A short - term aggregate exposure assessment was conducted to determine the total exposure for someone who would be exposed to sulfentrazone residues from both dietary and non - dietary routes over a short - term period (i.e. 1 - 7 days). A ggreg ate exposure to sulfentrazone was evaluated for two separate products (crop herbicide and residential lawn/turf herbicide). E xposure from these two uses occurred by multiple routes (dietary, dermal and incidental ingestion). A ggregation is conducted for dietary and non - dietary residential exposures and it is to represent reasonable conditions of exposure. The aggregate exposure estimates for all adults, adult females and toddlers were less than 100% of the PAD.

i. Food. The primary source for huma n exposure to sulfentrazone will be from ingestion of both raw and processed agricultural commodities from alfalfa, clover, citrus, tree nuts, berries and small fruit. A DRES chronic exposure assessment was previously conducted for asparagus, succulent li ma bean, cabbage, field corn forage, field corn stover, field corn grain, horseradish roots, dried shelled pea and bean (except soybean) subgroup 6C, peanut, peanut meal, peppermint tops, potato, spearmint tops, sugarcane, sugarcane molasses and sunflower seed, raw and processed commodities and presented in the Sulfentrazone; Establishment of Tolerances, Final Rule (FR / Vol. 68, No. 185: 55269 - 55280, September 24, 2003). A Tier 3 short - term exposure analysis has been performed to estimate the exposure for all adults, adult females, and toddlers (3 to 4 years of age) in the U.S. population for these raw and processed commodities. T his analysis utilized Dietary Exposure Evaluation Model (DEEM) software; field trial data fo r registered and pending crop uses; percent crop treated information; and consumption data from the USDA Continuing Surveys of Food Intake by Individuals (CSFIIs). Short - term dietary exposure estimates at the 99.9 th percentile for all adults, adult females and toddlers were < 2% of the PAD. The short - term dietary exposure to sulfentrazone has been demonstrated to be minimal.

ii. Drinking water. Based on the FIRST and SCI - GROW models the EECs of sulfentrazone plus its major metabolite 3 - carboxylic acid for acute exposures are estimat ed to be 35.8 ppb for surface water and 26 ppb for groundwater. T he EECs for chronic exposures are estimated to be 7.8 ppb for surface water and 26.0 ppb for ground water. 2. Non

- dietary exposure

. The primary source for human non - dietary exposure to sulfentrazone will be from post - application exposure to treated residential turfgrass. T he routes of sulfentrazone exposure were dermal post - application exposure for adults and toddlers, and post - appli cation incidental ingestion of sulfentrazone due to the hand - to - mouth behavior of toddlers. A worst case short - term non - dietary exposure analysis was conducted using algorithms anddefault factors published in US EPA’s Standard Operating Procedures (SOPs) for

Residential Exposure Assessments. T he dermal exposure estimates for all adults, adult females and toddlers were 0.013, 0.016 and 0.023 mg/kg/day, respectively. T he exposure estimate for incidental ingestion due to hand - to - mouth behavior for to ddlers was 0.0026 mg/kg/day. The resulting total (combined oral and dermal since the relevant endpoints both have the same effect) non - dietary exposure estimates were 0.013, 0.016 and 0.025 mg/kg/day for all adults, adult females and toddlers, respectively . D. Cumulative Effects Cumulative exposure to substances with 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 info rmation'' concerning the cumulative effects of a particular pesticide's residues and “other substances that have a common mechanism of toxicity.'' While the Agency has some information in its files that may turn out to be helpful in eventually determining whether a pesticide shares a common mechanism of toxicity with any other substances, EPA does not at this time have the capability to resolve the scientific issues concerning common mechanism of toxicity in a meaningful way. EPA is commencing a pilot proce ss to study this issue further through the examination of particular classes of pesticides. The Agency hopes that the results of this pilot process will enable the Agency to apply common mechanism issues to its pesticide risk assessments. At present, howev er, the Agency does not know how to apply the information in its files concerning common mechanism issues to risk assessments, and therefore believes that in most cases there is no “available information'' concerning common mechanism that can be scientific ally applied to tolerance decisions. Where it is clear that a particular pesticide may share a significant common mechanism with other chemicals, or where it is clear that a pesticide does not share a common mechanism with other chemicals, a Common mechani sm issues may affect tolerance decision. The Agency expects that most tolerance decisions will fall into the area in between, where EPA cannot reasonably determine whether a pesticide does or does not share a common mechanism of toxicity with other chemica ls (and, if so, how that common mechanism should be fa ctored into a risk assessment). In such circumstances, the Agency will reach a tolerance decision based on the best, currently - available and usable information, without regard to common mechanism issues . However, the Agency will also revisit such decisions when the Agency determines how to apply common mechanism information to pesticide risk assessments. In the case of sulfentrazone, EPA has determined that it does not now have the capability to apply th e information in its files to a resolution of common mechanism issues in a manner that would be useful in a risk assessment. This tolerance determination therefore does not take into account common mechanism issues. The Agency will reexamine the tolerances fo r sulfentrazone, if reexamination is appropriate, after the Agency has determined how to apply common mechanism issues to its pesticide risk assessments.E. Safety Determination

1. U.S. population. An oral NOEL of 25 mg/kg/day was used to determine dietary Margin of Exposures (MOEs) for all adults and adult females. This NOEL was derived from a prenatal oral developmental toxicity study in rats and was based on fetal death, reduced body weight and al terations in skeletal development. A dermal NOEL of 100 mg/kg/day was used to determine non - dietary (dermal) MOEs. This NOEL was derived from a dermal teratology rat study and was also based upon decreased fetal body weight and increased skeletal developme nt variations. A dditionally, the dermal absorption of 10% was used to estimate the absorbed (systemic) exposures for the aggregation of the oral and dermal route exposures (note: t his is only appropriate in cases such as this where the relevant endpoints have the same effect). T he acute dietary, non - dietary and aggregate MOEs for all US population is 5,646, for adults 20 - 49 years is 10,095, for females 13 - 49 years is 10,641, for youth 13 - 19 years is 7,621 and for children 3 - 5 years old is 3,904. F urther , the calculated short - term drinking water levels of concern (DWLOC) for all US population is 4,900 μg/L for adults 20 - 49 years is 4,900 μg/L, for females 13 - 49 years is 4,200 μg/L, for youth 13 - 19 years is 4,200 μg/L and for children 3 - 5 years old is 1,40 0 μg/L. T hese MOEs and DWLOC are considered to be acceptable and to clearly illustrate low risk potential.

2. Infants and children

. Risk to infants and children were determined by use of developmental toxicity studies in rats and a two - ge neration reproduction study in rats. The oral developmental toxicity studies resulted in a maternal NOEL of 25 mg/kg/day based on decreased body weight gain, increased spleen weight, and microscopic changes in the spleen, and a fetal NOEL of 10 mg/kg/day b ased on fetal death, reduced body weights, and alterations in skeletal development at higher doses. A dermal developmental toxicity study in rats resulted in a developmental (fetal) NOEL of 100 mg/kg/day based on decreased fetal body weight and increased i ncidences of fetal alterations, comprised primarily of skeletal variations and reductions in mean numbers of ossification sites. A two - generation reproduction study in rats resulted in a NOEL for systemic and reproductive/developmental parameters of 14 mg/ kg/day for males and 16 mg/kg/day for females. The LOEL for systemic and reproductive/development parameters was 33 mg/kg/day for males and 40 mg/kg/day for females. Systemic effects were comprised of decreased body weight gains, and reproductive/developme ntal effects at the LOEL included degeneration and/or atrophy of the testes, with epididymal sperm deficits in the second (F1) generation males. Male fertility in the F1 generation was reduced at higher doses; litter size, pup survival and pup body weight fo r both generations were also affected at higher doses. F FDCA section 408 provides that EPA shall 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 completenes s of the data base, unless EPA determines that such an additional factor is not necessary to protect the safety of infants and children. Based on current data requirements, the data base relative to pre - and post - natal toxicity is complete. EPA has determi ned that there is evidence of increased quantitative susceptibility following in - uteroexposure in the developmental toxicity studies in rats via the oral and dermal routes, and there is

evidence for increased qualitative susceptibility following pre natal and/or postnatal exposure in the 2 - generation reproduction study in rats. T he EPA performed A Degree of Concern Analysis and concluded that concerns are low for the quantitative susceptibility of rats fetuses observed following oral and dermal expos ures, the qualitative susceptibility of rabbit fetuses seen via the oral route, and the qualitative susceptibility seen in the 1 - and 2 - generation reproduction studies. The EPA concluded that there is a complete toxicity data base for sulfentrazone and ex posure data are complete or are estimated based on data that reasonably accounts for potential exposures. T he EPA determined that the 10X safety factor to protect infants and children should be reduced to 1X. T he percent of the RfD that will be utilized by the aggregate exposure to sulfentrazone for the most exposed subgroup would be < 2% of the PAD for children (1 to 6 years old) Therefore, EPA concludes that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to sulfentrazone.

F. International Tolerances There are no Codex Alimentarius Commission (Codex) Maximum Residue Levels (MRLs) for sulfentrazone.