Sulfentrazone Human - Health Risk Assessment DP# 364882

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### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### MEMORANDUM DATE: 22 - DEC - 2010 SUBJECT: Sulfentrazone ; REVISED Section 3 Registration Request to Add New Uses on:

Brassica , Head and Stem, Subgroup 5A; Brassica , L eafy Greens, Subgroup 5B; Melon Subgroup 9A; Fruiting Vegetable, Group 8 and Okra; Pea, Succulent; Flax; Strawberry ; and Tuberous and Corm Vegetable, Subgroup 1C. Human Health Risk Assessment. PC Code: 129081 DP Barcode: D 364882 Decision No.: 388050 Registration Nos : 279 - 3220 & 279 - 3189 Petition No.: 7E7308 Regulatory Action: Amended Section 3 Risk Assessment Type: Single Chemical/Aggregate Case No.: 7231 T XR No.: NA CAS No.: 122836 - 35 - 5 MRID No.: NA 40 CFR: §180.498 

### FROM: Kelly

L owe, Environmental Scientist Robert Mitkus, PhD, DABT, Toxicologist Chester Rodriguez, Ph.D., Pharmacologist William D. Wassell, Chemist Julie Van Alstine, MPH, Environmental Health Sc ientist Risk Assessment Branch 1 (RAB1) Health Effects Division (HED; 7509P) THROUGH: Dana M. Vogel, Branch Chief

George F. Kramer, Ph.D., Senior Chemist RAB1/HED (7509P) TO: Daniel Rosenblatt, Risk Manager 05

Registration Division (RD; 7505P) N OTE : This document supersedes Memo, L. Austin, et al. , 10/7/2008 (DP# 349558) and Memo, K. Lowe, et al. , 4/7/2009 (DP#362324) . This assessment has been updated to include revisions to the toxicological endpoints and an updated residential handler and pos tapplication assessment .Sulfentrazone Human - Health Risk Assessment DP# 364882

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### The HED of the Office of Pesticide Programs (OPP) is charged with estimating the risk to human health from exposure to pesticides. The RD of OPP has requested that HED evaluate hazard and exposure data and conduct dietary , occupational, residential, and aggregate exposure assessments, as needed, to estimate the risk to human health that will result from the proposed and registered uses of the herbicide sulfentrazone [N - (2,4 - dichloro - 5 - (4 - (difluoromethyl) - 4,5 - dihydro - 3 - methyl - 5 - ox o - 1 H - 1,2,4 - triazol - 1 - yl )phenyl)methanesulfonamide]. A summary

of the findings are provided in this document. The original risk assessment and hazard assessment were provided b y Li sa Austin (RAB1) ; the updated hazard assessment was provided b y Robert Mitkus and Chester Rodriguez (RAB1) ; the residue chemistry review and dietary exposure assessment s were prov ided b y William Wassell (RAB1) and Julie Van Alstine (RAB1); the occupational/residential exposure assessment and updated risk assessment w ere provided by

Kell y Lowe (RAB1); and the drinking water assessment was provided b y Michael Barrett of the Environmental Fate and Effects Division (EFED).Sulfentrazone Human - Health Risk Assessment DP# 364882

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### TABLE OF CONTENTS 1.0 Executive Summary ................................ ................................ ................................ ............ 4 2.0 Ingredient Profile ................................ ................................ ................................ ............ 10 2.1 Summary of Proposed Uses ................................ ................................ ................ 10 2.2 Structu re and Nomenclature ................................ ................................ ............. 14 2.3 Physical and Chemical Properties ................................ ................................ ..... 15 3.0 Hazard Characterization/Assessment ................................ ................................ ........... 15 3.1 Updated Toxicity Endpoint Selection ................................ ................................ 17 3.2 Food Quality Protection Act (FQPA) Considerations ................................ ..... 20 3.3 Endocrine Disruption ................................ ................................ ......................... 21 3.4 Recommendation for Aggregate Exposure Risk Assessments ........................ 22 4.0 Dietary Exposure/Risk Characterization ................................ ................................ ..... 22 4.1 Comparative Metabolic Profile ................................ ................................ ......... 22 4.2 Drinking Water Residue Profile ................................ ................................ ........ 23 4.3 Food Residue Profile ................................ ................................ ........................... 24 4.4 International Residue Limits ................................ ................................ ............. 36 4.5 Dietary Exposure Analyses ................................ ................................ ................ 36 5.0 Residential (Non - Occupational) Exposure/Risk Pathway ................................ .......... 38 5.1 Residential Handler Exposure ................................ ................................ ........... 38 5.2 Residential Post- application Exposure ................................ ............................. 39 5.3 Spray Drift ................................ ................................ ................................ ........... 41 6.0 Aggregate Risk Assessments and Risk Characterization ................................ ............ 41 6.1. Short- and Intermediate - Term Aggregate Risk ................................ ............... 42 7.0 Cumulative Risk Characterization/Assessment ................................ ........................... 43 8.0 Occupational Exposure/Risk Pathway ................................ ................................ .......... 43 8.1 Occupational Handler Exposure ................................ ................................ ....... 43 8.2 Occupational Post- application Exposure ................................ .......................... 50 9.0 Data Needs and Label Recommendations ................................ ................................ .... 51 9.1 Toxicology ................................ ................................ ................................ ............ 51 9.2 Residue Chemistry ................................ ................................ .............................. 51 9.3 Occupational and Residential Exposure ................................ ........................... 52Sulfentrazone Human - Health Risk Assessment DP# 364882

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### 1.0 Executive Summary Sulfentrazone is an aryl triazolinone herbicide used to control a variety of broadleaf weeds. The mode - of - action for controlling emerging weeds is by protoporphyrinogen oxidase (PPO) inhibition. Sulfentrazone acts by the same mechanism as the diphenyl ether herbicides in which membrane disruption is initiated by the inhibition of PPO in the chlorophyll biosy nthetic pathway and leads to the subsequent build - up of toxic intermediates. Plants emerging from soils treated with sulfentrazone turn necrotic and die shortly after exposure to light (s ource: http://courses.cropsci.ncsu.edu/cs414/CH_11.PDF ). The Interregional Research Project No. 4 (IR - 4) has submitted a petition proposing the establ ishment of permanent tolerances for the combined residues of the herbicide sulfentrazone [N - [2,4 - dichloro - 5 - [4 - (difluoromethyl) - 4,5 - dihydro - 3 - methyl - 5 - oxo - 1 H - 1,2,4 - triazol - 1 - yl ]phenyl]methanesulfonamide] and its metabolites HMS [N - (2,4 - dichloro - 5 - (4 - (difluoromethyl) - 4,5 - dihydro - 3 - hydrox ym ethyl - 5 - oxo - 1 H - 1,2,4 - triazol yl )phenyl )methanesulfonamide)] and DMS [( N - 2,4 - dichloro - 5 - [4 - (difluoromethyl) - 4,5 - dihydro 5 - oxo - 1 H - 1,2,4 - triazol - 1 - yl )phenyl)methanesulfonamide] in/on: Brassica , head and stem, subgroup 5A * ..................... 0. 20 ppm Brassica , leafy

greens, subgroup 5B ........................... 0.40 ppm Melon, subgroup 9A ................................ ................... 0.15 ppm Vegetable, fruiting, group 8 ................................ ........ 0.15 ppm Okra ................................ ................................ ............. 0.15 ppm Pea, succulent ................................ .............................. 0.15 ppm Flax ................................ ................................ ............. 0.15 ppm Strawberry ................................ ................................ ... 0.15 ppm Vegetable, tuberous and corm, subgroup 1C * ............ 0.15 ppm Cocona ................................ ................................ ........ 0.15 pp m Eggplant, African ................................ ........................ 0.15 ppm Eggplant, pea ................................ ............................... 0.15 ppm Eggplant, scarlet ................................ .......................... 0.15 ppm Goji berry ................................ ................................ .... 0.15 ppm Huckleberry , garden ................................ .................... 0.15 ppm Marty nia ................................ ................................ ...... 0.15 ppm Naranjilla ................................ ................................ ..... 0.15 ppm Roselle ................................ ................................ ......... 0.15 ppm Sunberry ................................ ................................ ...... 0.15 ppm Tomato, bush ................................ ............................... 0.15 ppm Tomato, currant ................................ ........................... 0.15 ppm Tomato, tree ................................ ................................ 0.15 ppm * Individual tolerances are established for residues in/on cabbage at 0.20 ppm and potato at 0.15 ppm. 

### A tolerance is currently

established under 40 CFR §180.498(a)(1) for the combined residues of sulfentrazone and its major metabolite, HMS in/on soy bean seed at 0.05 ppm. In addition,Sulfentrazone Human - Health Risk Assessment DP# 364882

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### permanent tolerances are established under 40 CFR §180.498(a)(2) for the combined residues of sulfentrazone and its metabolites HMS and DMS in/on several food commodities; these established tolerances range from 0.15 ppm (various plant commodities) to 0.40 ppm (peanut meal). Time - limited tolerances for the combined residues of sulfentrazone and its metabolites HMS and DMS have been established under 40 CFR § 180.498(b) in connection with Section 18 Emergency

Ex emptions ; these include tolerances for residues in/on bean, succulent- seed without pod (lima bean & cowpea) at 0.1 ppm with a 12/31/07 expiration date, flax seed at 0.2 ppm with a 12/31/10 expiration date, and strawberry at 0.60 ppm with a 12/31/10 expiration date. Finall y, tolerances are established under 40 CFR § 180.498(d) for inadvertent and indirect combined residues of sulfentrazone and its metabolites HMS and DMS in/on cereal grain (excluding sweet corn) bran, forage, grain, hay , hulls, stover, and s traw at 0.1 - 0.6 ppm as a result of the application of sulfentrazone to growing crops. The sulfentrazone end - use products (EPs) relevant for this registration request are Spartan ® 

### Herbicide (EPA Reg. No. 279 - 3189; 75% dry- flowable or DF formulation) and Sp artan ® 

### 4F Herbicide (EPA Reg. No. 279 - 3220; 4 pounds ( lb ) /gal flowable - concentrate (FlC) formulation). IR- 4 requests the amendment of these EP labels to incorporate new uses on head and stem Brassica , leafy

greens Brassica , fruiting vegetables including okra, melons, strawberry , succulent peas and beans, and flax. These EPs are proposed for: (i) preplant or preemergence applications on all of the above - listed crops at maximum seasonal rates of 0.1875 - 0.375 pounds active ingredient ( lb ai ) / acre ( A) using ground or aerial equipment; and (ii) postemergence applications on fruiting vegetables at a maximum seasonal rate of 0.375 lb ai/A. No pre - harvest intervals (PHIs) were proposed for these crops. In addition, this document includes an updated residential assessment using the maximum application rate allowed on current sulfentrazone labels with registered residential uses. Hazard Assessment Sulfentrazone inhibits the enzy me p rotoporphyrinogen oxidase ( PPO ) in target plants, and the re sults of mammalian toxicity studies were consistent with this mechanism of action, given that PPO is an important enzy me in the heme s ynthetic pathway in mammals. Specificall y, disruption of heme sy

nthesis was observed in mice, rats, and dogs, and this wa s seen at about the same dose levels across species, except in the case of mice, where the effects were seen at a slightly higher dose . In addition, this hematotoxicity occurred around the same dose level from short - through long - term exposure without inc reasing in severity . Sulfentrazone is also a developmental toxicant. Developmental effects including decreased fetal body weights and reduced/delayed skeletal ossifications were observed in both the oral and dermal developmental toxicity studies in the rat and at doses that were not m aternally toxic, although clear No Observed Adverse Effect L evels (NOAELs ) were attained in both studies . In the 2 - generation reproduction study in rats, offspring effects such as decreased body weights and decreased litter survival were observed at a maternall y toxic dose (slightly decreased body weight gain). Although sulfentrazone is considered a developmental toxicant, the developing nervous sy stem is not considered a selective target . A published non - guideline developm ental neurotoxicity study in the rat by De Castro et al. (2007) with no established NOAEL failed to demonstrateSulfentrazone Human - Health Risk Assessment DP# 364882

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### conclusively

developmental neurotoxicity and yi elded developmental effects more related to those observed in the rat 2 - generation reproductive toxicity study for which a clear NOAEL was established. Available acute and subchronic neurotoxicity studies with well - defined NOAELs indicate neurotoxic effects (e.g., an increased incidence of clinical signs of toxicity and motor activity changes ) at rel atively high administered doses (LOAELs of 750 mg/kg and 150(M)/180(F) mg/kg/day for acute and subchronic studies , respectively) that are more consistent with sy stemic toxicity rather than neurotoxicity . Furthermore, there is no evidence of neuropathology in any of the studies available for sulfentrazone . Thus, based on the weight of evidence , a developmental neurotoxicity (DNT) study is unlikely to yield a lower point of departure than the one being used for this risk assessment and therefore not require d. Carcinogenicity studies in rats and mice showed no evidence of increased incidence of tumor formation due to treatment with sulfentrazone, and s ulfentrazone is n ot considered to be genotoxic . Exposure Assessment Dietary Exposure and Risk The acute an d chronic dietary exposure and risk assessments were conducted using the Dietary Exposure Evaluation Model - Food Consumption Intake Database (DEEM - FCID  , ver. 2.03). The acute and chronic analy se s assumed DEEMTM (ver. 7.81) default processing factors, 10 0% crop - treated (CT) , and tolerance - level residues for all commodities. The analyse s also incorporated the drinking water estimates provided by EFED ( 0.0358 ppm and 0.026 ppm for the acute and chronic anal ys is, respectivel y) . The resulting acute ( food plus water) risk estimates are below HED ’s level of concern [<100% of the acute population - adjusted dose (aPAD)] at the 95 th 

### percentile of the exposure distribution for the U.S. general population ( less than 1 .0 % aPAD), and all population subgroups . The aPAD is lower for females 13 to 49 years old . The population subgroup with the greatest risk was females 13 - 49 years old , which utilized less than 3 .0 % of the aPAD. The resulting chronic risk estimates are below HED’s level of concer n. The most highly

exposed population subgroup was children 1 - 2 years old , which utilized less than 4 .0 % of the chronic PAD (cPAD). Aggregate Risk Acute and chronic aggregate risks are made up only of dietary

sources; therefore, the exposure estimates provided in the dietary exposure anal ys is represent acute and chronic aggregate exposure, respectivel y. An aggregate cancer risk assessment was not performed because sulfentrazone is not considered to be a carcinogen. Short - and intermediate - term aggregate risks are made up of dietary

and non - dietary

sources of exposure. Since sulfentrazone is proposed for use on turf, residential handler and post - application exposure is expected. Short - term exposures exist for adults and children from the registered turf application use ; however, since the short and intermediate - term points of departure are the same, the short - term aggregate is protective of intermediate - term exposures . Short - and intermediate - term aggregate risk s are made up of average dietary

exposures from food and drinking water sources plus dermal and oral (children only) residential exposures. Dietary (food and drinking water) exposure is based on a Tier 1 chronic dietary

exposure assessment. The aggregate short - and intermediate - term MOEs are ≥100; therefore, aggregate exposures to sulfentrazone are not of concern to HED.Sulfentrazone Human - Health Risk Assessment DP# 364882

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### Residential Exposure Estimates Sulfentrazone is already registered on turf, including residential lawns and golf courses. It is anticipated that there is potential for both residential handler and postapplication exposure from the registered uses. Based on the use pattern and label information regarding re - treatment, only short - term exposures are expected; however, the points of departure for short - and intermediate term der mal and inhalation routes are the same and thus the short - term assessment is protective of intermediate - term exposures. All residential handler exposure and risk estimates are below H ED’s level of concern (MOEs ≥ 100) . Short - and intermediate - term dermal postapplication risks were assessed for adults, 10 - 12 year olds , and 3 - <6 year olds and did not exceed HED’s level of concern for all residential postapplication scenarios. Short - and intermediate - term incidental oral postapplication risks were assessed for 3 - <6 year olds after applications of sulfentrazone to lawns and did not exceed HED’s level of concern. Occupational Exposure Estimates Sulfentrazone is proposed as a soil - applied herbicide for the control of susceptible broadleaf, grass , and sedge weeds on head and stem Brassica , leafy green Brassica , melons, fruiting vegetables, okra, succulent peas, flax, strawberry , and tuberous and corm vegetables, and also impregnation to dry

bulk fertilizer and application with dry fertilizer. Soil applications of sulfentrazone must be made before crop germination to prevent injury to the emerging crop seedlings. Sulfentrazone may be applied to the soil at earl y preplant, preplant incorporated, or preemergence using aerial, chemigation, and groundboom application equipment. Sulfentrazone also may be applied as a hooded postemergence spray between the rows of fruiting vegetables and okra using shielded groundboom equipment. For both foliar and dry

bulk fertilizer applications , none of the scenarios assessed have risks of concern with the addition of chemical - resistant gloves (as recommended on the label). Post application risks were assessed and were found to not exceed HED’s level of concern on Day 0 (12 hours following application). Therefore, the restricted - entry interval (REI) is based on the acute toxicity

of sulfentrazone technical material which is classified as Category III for acute dermal toxicity

and eye irritation potential and Category IV for skin irritation potential. Sulfentrazone is not a dermal sensitizer. Under the Worker Protection Standard (WPS) for Agricultural Pesticides, active ingredients classified as acute toxicity categories III or IV for these routes are assigned a 12 - hour REI. Therefore, the 12 - hour REI that appears on the proposed label is adequate. Review of Human Research This exposure/risk assessment relies in part on data from studies in which adult human subjects were intentionall y exposed to a pesticide to determine their dermal and inhalation exposure. Many such studies, involving exposure to many different pesticides, comprise generic pesticide exposure databases such as the Pesticide Handlers Exposure Database (PHED), the Outdoor Residential Exposure Task Force (ORETF) Database , and the Agricultural Reentry Task Force (ARTF) Database. EPA has reviewed all the studies in these multi - pesticide generic exposure databases, and on the basis of available evidence has found them to have been neither fundamentall y unethical nor s ignificantly deficient relative to standards of ethical researchSulfentrazone Human - Health Risk Assessment DP# 364882

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### conduct prevailing when they were conducted. There is no regulatory barrier to continued reliance on these studies, and all applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied. Environmental Justice Considerations Potential areas of environmental justice concerns, to the extent possible, were considered in this human - health risk assessment, in accordance wi th U.S. Executive Order 12898, Federal Actions to Address Environmental Justice in Minority Populati ons and L ow - Income Populations, (http://www.hss.energy .gov/nuclearsafety/ env/guidance/justice/eo12898.pdf ). As a part of every

pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well - established procedures. In line with OPP policy , HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and ac tivities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the USDA under the Continuing Survey s of Food Intakes by Individuals ( CSFII) and are used in pesticide risk as sessments for all registered food uses of a pesticide. These data are anal yz ed and categorized by

subgroups based on age, season of the year, ethnic group, and region of the country . Additionally , OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non - dietary

exposures based on home use of pesticide products and associated risks for adult applicators and for 3 - <6 ye ar olds , 10 - 12 year olds , and adults entering or playing on treated areas post - application are evaluated. Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized software and models that consi der exposure to by standers and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups. Regulatory Recommendations Provided a revised Section B (proposed use directions), a revised Section F (propo sed tolerances), and a reference standard for the metabolite HMS are submitted , the residue chemistry , toxicology , and occupational exposure databases support conditional registration and establishment of permanent tolerances. The proposed uses and the submitted data support the establishment of the following tolerances for the combined residues of sulfentrazone and its metabolites HMS and DMS in/on:

Brassica , head and stem, subgroup 5A ....................... 0.20 ppm Brassica , leafy

greens, subgroup 5B ........................... 0. 40 ppm Melon subgroup 9A ................................ .................... 0.15 ppm Vegetable, fruiting, group 8 ................................ ........ 0.15 ppm Okra ................................ ................................ ............. 0.15 ppm Pea, succulent ................................ .............................. 0.15 ppm Flax ................................ ................................ ............. 0.15 ppm Strawberry ................................ ................................ ... 0.15 ppm Vegetable, tuberous and corm, subgroup 1C .............. 0.15 ppm Cocona ................................ ................................ ........ 0.15 ppmSulfentrazone Human - Health Risk Assessment DP# 364882

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### Eggplant, African ................................ ........................ 0.15 ppm Eggplant, pea ................................ ............................... 0.15 ppm Eggplant, scarlet ................................ .......................... 0.15 ppm Goji berry ................................ ................................ .... 0.15 ppm Huckleberry , garden ................................ .................... 0.15 ppm Marty nia ................................ ................................ ...... 0.15 ppm Naranjilla ................................ ................................ ..... 0.15 ppm Roselle ................................ ................................ ......... 0.15 ppm Sunberry ................................ ................................ ...... 0.15 ppm Tomato, bush ................................ ............................... 0.15 ppm Tomato, currant ................................ ........................... 0.15 ppm Tomato, tree ................................ ................................ 0.15 ppm Data Needs/Deficiencies Toxicol ogy

 Immunotoxicity

study (40 CFR revised Part 158 data requirement) . Residue Chemistry

 Revised Section B (for conditional registration).  Revised Section F (for conditional registration).  As the reference standard for the metabolite HMS has expired 4/1 /2008, the petitioner should submit a new standard (for conditional registration). If new standards are being submitted, they should be sent to the ACL , which is located at Fort Meade, to the attention of Theresa Cole at the following address: USEPA National Pesticide Standards Repository /Anal ytical Chemistry Branch/OPP 701 Mapes Road Fort George G. Meade, MD 20755 - 5350 Please note that the extended zip code is required for delivery . Occupational and Residential Exposure

 None Note s to RD: (1) As the enforcement method for plant commodities determines free and conjugated forms of the anal yt es, the tolerance expression should be revised to indicate tolerances are established for combined residues of free and conjugated forms of sulfentrazone, and its metabolites HMS and DMS . T olerances should be proposed using this tolerance expression. A s the proposed directions for use on fruiting vegetables include postemergence applications, HED concludes metabolism data are not available to support the post emergence applications.Sulfentrazone Human - Health Risk Assessment DP# 364882

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### (2) The commodity definitions under 180.498(d) for Grain, cereal, forage, fodder and atraw [sic] , group 16, except sweet corn; forage; Grain, cereal, forage, fodder and atraw [sic] , group 16, except sweet corn; hay ; Grain, cereal, forage, fodder and atraw [sic] , group 16, except sweet corn; stover; and Grain, cereal, forage, fodder and atraw [sic] , group 16, except sweet corn; straw should be corrected to Grain, cereal, forage, fodder and straw, group 16, except sweet corn; forage; Grain, cereal, forage, fodder and straw, group 16, except sweet corn; hay ; Grain, cereal, forage, fodder and straw, group 16, except sweet corn; stover; and Grain, cereal, forage, fodder and straw, group 16, except sweet corn; straw. (3) For fruiting v egetable crop group 8, the petition and labels for the current action list only those crops included in the current crop grouping. However, as requested by RD, HED assessed those crops proposed for the new expanded fruiting vegetable crop group 8 - 10. The Registrant should update their labels as appropriate. 2.0 Ingredient Profile Sulfentrazone is an aryl triazolinone herbicide used to control a variety of broadleaf weeds. The mode - of - action for controlling emerging weeds is by P PO inhibition. Sulfentrazone acts b y the same mechanism as the diphenyl ether herbicides in which membrane disruption is initiated by the inhibition of PPO in the chlorophyl l biosy nthetic pathway

and leads to the subsequent build up of toxic intermediates . Plants emerging from soils treated with sulfentrazone turn necrotic and die shortly

after exposure to light. 2.1 Summary of Proposed Uses IR- 4 is requesting new uses of sulfentrazone on head and stem Brassica , leafy greens Brassi ca , fruiting vegetables including okra, melons, strawberry , succulent peas and beans, and flax. The proposed products are intended for: (i) preplant or preemergence applications on all of the above - listed crops at maximum seasonal rates of 0.1875 - 0.375 lb ai/A using ground or aerial equipment; and (ii) postemergence applications on fruiting vegetables at a maximum seasonal rate of 0.375 lb ai/A. No pre - harvest intervals (PHI s) were proposed for these crops. A list of the sulfentrazone end - use products r elevant to this registration request is presented in Table 2.1.1 . The proposed crop use directio ns are summarized in Table 2.1.2 . Information regarding rotational crop restrictions is listed in Table 2.1.3 .Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 11 of 58 Table 2.1.1 . Summary of Proposed End - Use Pr oducts. Trade Name Reg. No. ai (% of formulation) Formulation

Type 1 Target Crops Target Pests Label Date Spartan ® 4F Herbicide 279 - 3220 39.6 (4 lb/gal) FlC Row Crops: corn (field, seed, and pop); peanut; potato; soybean; sugarcane; sunflower; tobacco. Vegetable Crops: asparagus; Brassica , head and stem; Brassica , leafy greens; cabbage (transplant only); dry shelled beans and peas; fruiting vegetables (except cucurbits) and okra; horseradish; melons; strawberry; succulent peas and beans; Oil Crops: f

lax; mint. Broadleaf, grass,

and sedge weeds. Specimen label

code: Spartan4F _3_12 - 17 - 07 Spartan ® Herbicide 279 - 3189 75 DF Specimen label code: Spartan _3_12 - 17 - 07

1 FlC = flowable - concentrate formulation; DF = dry- flowable formulation. Table 2.1. 2 . Summary of Proposed Directions for Use of Sulfentrazone. Applic. Timing, Type, and Equip. Formulation

[EPA Reg. No.] Applic. Rate, lb ai/A [Soil Type] Max. No. Applic.

per Season Max. Seasonal

Applic. Rate (lb ai/A) PHI

(days) Brassica , Head and Stem [broccoli, Chinese broccoli, Brussels sprouts, Chinese (napa) cabbage, Chinese mustard, cauliflower, cavalo broccoli, kohlrabi] Early preplant, preemergence, preplant incorporated 4 lb/gal FlC [279 - 3220] 0.070 - 0.281

[coarse] 0.094 - 0.375 [medium and fine] Not specified (NS) 0.375 NS 75% DF [279 - 3189] Use Directions and Limitations : Do not incorporate to depths greater than 2 inches. Brassica , Leafy Greens [broccoli raab, Chinese (bok choy) cabbage, collards, kale, mizuna, mustard greens, mustard spinach, rape greens] Early preplant, preemergence, preplant incorporated 4 lb/gal FlC [279 - 3220] 0.070 - 0.281

[coarse] 0.094 - 0.375 [medium and fine] NS 0.375 NS 75% DF [279 - 3189] Use Directions and Limitations : Do not incorporate to depths greater than 2 inches. Fruiting Vegetables (except curcurbits) [eggplant, groundcherry (Physalis spp), pepino, pepper (includes bell pepper, chili

pepper, cooking pepper, pimento, sweet pepper), tomatillo, tomato] and okraa Preplant banded or postemergence with 4 lb/gal FlC [279 - 3220] 0.070 - 0.281

[coarse] 0.094 - 0.375 NS 0.375 NSSulfentrazone Human - Health Risk Assessment DP# 364882

Page 12 of 58 Table 2.1. 2 . Summary of Proposed Directions for Use of Sulfentrazone. Applic. Timing, Type, and Equip. Formulation

[EPA Reg. No.] Applic. Rate, lb ai/A [Soil Type] Max. No. Applic.

per Season Max. Seasonal

Applic. Rate (lb ai/A) PHI

(days) shielded/hooded sprayer 75% DF [279 - 3189] [medium and fine] Use Directions and Limitations : None. Succulent Peas and Beans [bean (Phaseolus; includes green lima bean and succulent broad bean), bean ( Vigna ; includes blackeyed pea, cowpea, southern pea), pea ( Pisum ; includes English pea, garden pea, green pea); pigeon pea Preemergence 4 lb/gal FlC [279 - 3220] 0.070 - 0.1875

[coarse] 0.094 - 0.1875 [medium] 0.117 - 0.1875 [fine] NS 0.1 875 NS 75% DF [279 - 3189] Use Directions and Limitations : Do not incorporate. Flax Preemergence 4 lb/gal FlC [279 - 3220] 0.070 - 0.281

[coarse] 0.094 - 0.375 [medium and fine] NS 0.375 NS 75% DF [279 - 3189] Use Directions and Limitations : Do not apply directly on crop after the crop emergence or if the seedling sprouts are close to the soil surface.

Melon [citron melon, muskmelon, watermelon] Preemergence 4 lb/gal FlC [279 - 3220] 0.093 - 0.1875

[coarse] 0.093 - 0.2125 [medium] 0.117 - 0.25 [fine] NS 0.25 NS 75% DF [279 - 3189] Use Directions and Limitations : Do not apply directly on crop after the crop emergence or if the seedling sprouts are close to the soil surface. Strawberry Preemergence 4 lb/gal FlC [279 - 3220] 0.070 - 0.281

[coarse] 0.0 94 - 0.375 [medium and fine] NS 0.375 NS 75% DF [279 - 3189] Use Directions and Limitations: Do not apply directly on crop after the crop emergence or if the seedling sprouts are close to the soil surface. a. The current label and petition list only those crops currently listed under the fruiting vegetable crop group 8. However, this risk

assessment was conducted for those crops proposed under the expanded crop group. 

### The following restrictions apply to all proposed crops: Application rates are de pendent on soil texture, percent organic matter (%OM), and pH. Use on soils classified as sand which have <1% OM is prohibited. Applications are to be made in a minimum of 10 gallons per acre (GPA) using ground equipment or a minimum of 5 GPA using aeria l equipment.Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 13 of 58 Table 2.1.3 . Plantback Intervals for Use of Sulfentrazone.

Rotational Crop 1 Plantback Interval (months) Alfalfa 12 Barley 4 Cabbage Anytime Canola 24 Cereal Grains (Buckwheat, Oats, Pearl Millet, Proso Millet, Teosinte, Wild Rice) 12 Corn, Field 10 Corn, Pop 18 Corn, Sweet 18 Cotton 18 Dry Shell Peas and Beans Anytime Horseradish Anytime Limas Anytime Mint Anytime Peanuts Anytime Potatoes Anytime Rice 10 Rye 4 Sorghum 10 2 Soy bean Anytime Sugar Beets 36 Sugarcane Anyti me Sunflowers Anytime Sweet Potatoes 12 Triticale 4 Tobacco Anytime Turf Anytime Wheat 4 1 For all other crops not listed, the rotation interval is a minimum of 12 months. 2 Sorghum

– 18 - mo nth rotation for rates above 8.0 oz/A. 

### Conclusions : The use directions are adequate to allow HED to conduct an assessment of whether the submitted residue data reflect the maximum residues likely to occur. However, three revisions are requested: (1) The label for Spartan ® 

### 4F Herbicide (EPA Reg. No. 279 - 3220) , a 4 lb/gal FlC (liquid) formulation, should be modified to correct the application rates listed as “dry ounces Spartan ® 

### Herbicide per acre” to “fluid ounces Spartan ® 

### Herbicide per acre . ” (2) A s metabolism data are not available to support postemergenc e applications on fruiting vegetables (except cucurbits ), these proposed uses should be limited to preemergence application only . (3) The proposed labels should be revised to specify a maximum single and seasonal application rate of 0.20 lb ai/A to Brassica leafy greens, subgroup 5B, as this rate is supported by the submitted crop field trial data for mustard greens. A revised Section B is required.Sulfentrazone Human - Health Risk Assessment DP# 364882

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### 2.2 Structure and Nomenclature Table 2.2. Structure and Nomenclature of Sulfentrazone and Its Metab olites. Chemical structure

Cl Cl

N H S O 2 CH 3

N N N O CH 3

CH F 2

Common name Sulfentrazone Com pany experimental name F6285; FMC 97285 IUPAC name 2',4' - dichloro - 5' - (4 - difluoromethyl - 4,5 - dihydro - 3 - methyl - 5 - oxo - 1 H - 1,2,4 - triazol 1 - yl) methanesulfonanilide CAS name N - (2,4 - dichloro - 5 - (4 - (difluoromethyl) - 4,5 - dihydro - 3 - methyl - 5 - oxo - 1 H - 1,2,4 - triazol - 1 - yl)phenyl)methanesulfonamide CAS registry number 122836 - 35 - 5 End - use product (EP) 4 lb/gal FlC formulation (Spartan® 4F Herbicide; EPA Reg. No. 279 - 3220) and 75% DF formulation (Spartan® Herbicide; EPA Reg. No. 279 - 3189) Chemical structure of DMS metabolite

Cl Cl

N H S O 2 CH 3

N N N O C H F 2

Common name 3 - desmethyl sulfentrazone; DMS Chemical name N - (2,4 - dichloro - 5 - (4 - (difluoromethyl) - 4,5 - dihydro - 5 - oxo - 1 H - 1,2,4 - triazol - 1 - yl)phenyl)meth anesulfonamide Chemical structure of HMS metabolite

Cl Cl

N H S O 2 C H 3

N N N O C HF 2

O H

Common name 3 - hydroxymethyl sulfentrazone; HMSSulfentrazone Human - Health Risk Assessment DP# 364882

Page 15 of 58 Table 2.2. Structure and Nomenclature of Sulfentrazone and Its Metab olites. Chemical name N - (2,4 - dichloro - 5 - (4 - (difluoromethyl) - 4,5 - dihydro - 3 - hydroxymethyl - 5 - oxo - 1 H1,2,4 - triazol - 1 - yl)phenyl)methanesulfonamide 

### 2.3 Physical and Chemical Properties Table 2.3 Physicochemical Properties of Technical Grade Sulfentrazone.

Parameter Value Reference Melting range 120 - 122 oC DP# 288712, 3/6/03, G. Kramer, G. Reddy, and L. Liu pH 4.78 at 23 oC Density 0.53 g/cm3 Water solubility 4.0 x 10 2 μg/g Solvent solubility 18.6% w /w in acetonitrile Vapor pressure 8 x 10 - 10 mm Hg Dissociation constant, pKa 6.56 Octanol/water partition coefficient, Log(KOW) 1.49 at pH 5 UV/visible absorption spectrum Not available 

### 3.0 Hazard Char acterization/Assessment A detailed hazard characterization and dose response assessment for sulfentrazone were presented in previous HED risk assessment s in 2003 and 2009 ( D274568 and D362324 ). However, both the hazard characterization and toxicity profi le tables have been updated since the 2009 risk ass essment based on additional discussion with the registrant . Sulfentrazone has low acute toxicity via the oral, dermal , and inhalation routes (Toxicity Category III). It is a mild eye irritant (Toxicity Category III), but not a dermal irritant or sensitizer. No sy stemic toxicity was seen via the dermal route up to the limit dose (1 , 00 0 mg/kg/day) in a 28 - day

dermal toxicity

study in non - pregnant ra

bbi ts. Sulfentrazone inhibits the enzy me PPO in target plants, and the results of mammalian toxicity studies were consistent with this mechanism of action, given that PPO is an important enzy me in the heme sy

nthetic pathway in mammals . Specifically, disruption of heme s ynthesis was observed in mice, rats, and dogs, and this was seen at about the same dose levels across species, except in the case of mice, where the effects were seen at a slightly higher dose . In addition, this hematotoxicity occurred around the same dose level from short - through long - term exposure without increasing in severity . Sulfentrazone is a developmental toxicant. Developmental effects including decreased fetal body weights and reduced/delayed skeletal ossifications were observed in both the oral and dermal developmental toxicity s tudies in the rat, as well as at doses that were not m aternally toxic, although clear NOAEL s were attained in both studies . Inrabbits, developmental effects such as decreased pup viability were observed at a maternall y toxic dose (clinical signs of toxic ity, abortions , and decreased body- weight gains). In the 2 - generation reproductive toxicity study in rats, developmental effects included an increased duration of gestation, reduced prenatal viability (fetal and litter), reduced litter size, and an increa sed number of stillborn pups. PupSulfentrazone Human - Health Risk Assessment DP# 364882

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### body weight deficits along with reduced pup and litter postnatal survival were also observed. All of the developmental effects were reported in the presence of mild maternal toxicity (slightl y decreased body- weight gain, particularl y in F1 females) In the acute neurotoxicity (ACN) study , an increased incidence of clinical signs of toxicity (staggered gait, splayed hind limbs , and abdominal gripping), changes in functional observation battery (FOB) parameters , and decreas ed motor activity were observed at ≥750 mg/kg/day ; however, c omplete recovery was observed in 14 day s and there was no evidence of neuropathology . In the subchronic neurotoxicity (SCN) study , clinical signs of toxicity, increased motor activity , and/or decreased body weights, body- weight g ain, and food consumption were observed at ≥150 mg/kg/day ; however, there was no evidence of neuropathology

due to treatment and the effect on motor activity was not consistent with that observed in the ACN . Clear NOAELs were attained in both the acute an d subchronic neurotoxicity

studies. In a published, non - guideline developmental toxicity study in the rat ( De Castro VL , Destefani CR , Diniz C , Poli P . 2007. Evaluation of neurodevelopmental effects on rats exposed prenatall y t o sulfentrazone. Neurotoxicology 28(6):1249 - 59.) , several dose dependent effects were reported in pups whose mothers were treated with ≥25 mg/kg/day sulfentrazone on gestation day (GD) 1 - 6 or GD 6 - 15 (summarized in 2009 risk assessment; D362324). However, this study had several shortcomings that limit its use for regulatory purposes. First, most of the effects observed involved measures of phys ical and reflex development, known to be affected b y body weight. Although the published study failed to report body weight, the doses used were taken from the guideline reproduction study and are already known to be associated with weight loss. Furthermore, the reported data, study methods, statistical methods used, and statistical results contained numerous errors, omissions and uncertainties. For example, the study authors failed to report critical data such as pup birth weight and body weight , erroneousl y reported the exact same data for the number of pups born alive in the two groups, incorrectly reported “interaction” effects associated with an ANOVA test for overall effects to somehow indicate evidence of specific effects between a treatment group and the control, failed to instead report results for the more appropriate test for multiple comparisons, Dunnett’s test, that they had cited as having used, similarly misrepresented the non -parametric Kruskal - Wallis test results to be pairwise comparisons, inconsistently reported standard errors and/or standard deviations (e.g. , omitted error bars in locomotion and mother’s behavior responses, reported standard deviation rather than standard error in Fig. 2), unclearl y explained how subsets of rats were allocated for some of the tests, inexplicably omitted female pups from some tests, and reported a dose - related effect in eye - opening contradictory to the relationship shown in the graph (Fig. 2). The published study

was not designed to produce a N OAEL and therefore only used doses found to cause effects in guideline studies. Due to the uncertainty and unreliability associated with the published study ’s reported results, the EPA employed an independent statistical method (Cummings, 2007) in an effo rt to glean whether the effects observed at the tested treatment levels seemed consistent with effects observed in other studies at these same levels. HED believes that the results are consistent with what was observed in the reproduction study and that the NOAEL for that study can be extrapolated to the published study .Sulfentrazone Human - Health Risk Assessment DP# 364882

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### Carcinogenicity studies in rats and mice showed no evidence of increased incidence of tumor formation due to treatment with sulfentrazone, and HED previousl y classified sulfentrazone as “not likely

to be carcinogenic to humans” in accordance with EPA proposed Guidelines for Carcinogenic Risk Assessment (April 10, 1996). The available mutagenicity studies indicate that sulfentrazone is weakl y clastogenic in the in vitro mouse ly mphoma assay i n the absence of S9 activation; however, the response was not evident in the presence of S9 activation. Sulfentrazone is neither mutagenic in bacterial cells nor clastogenic in male or female mice in vivo . Sulfentrazone is readil y absorbed from the GI tract of rats following oral dosing and nearl y all radioactivity

was recovered in the urine (84 - 104% of the dose) and feces (~ 6%) within 72 hours. There were no major sex - related differences in the pattern of excretion and no evidence of bioaccumulati on. 3.1 Updated Toxicity Endpoint Selection The doses and toxicological endpoints selected for several exposure scenarios have been updated since the last risk assessment ( D362324 ; 2009). The rationale for any changes is provided below and the updated endpoints are included in Table 3.1. The updated endpoints are protective of sulfentrazone’s developmental toxicity, which was the critical effect in the database and observed via both the oral and dermal routes of exposure. Acute Dietary Endpoint ( Females 13 - 49 yrs old): The acute dietary endpoint is based on increased gestation duration, reduced prenatal viability (fetal and litter), reduced litter size, increased number of stillborn pups, reduced postnatal survival (pups and litter), and pup body wei ght deficits throughout lactation in both generations of offspring observed in a 2 - generation reproductive toxicity

study in rats. The developmental effects were reported in the presence of mild maternal toxicity (slightly decreased body- weight gain , particularl y in F1 females ) . It has been HED’s practice to consider various forms of developmental toxicity such as reduced prenatal viability , reduced litter size, and increased number of stillborn pups as single - dose effects and , therefore , relevant for the acute dietary (females aged 13 - 49) exposure scenario, in order to protect against potential exposure of pregnant females. It should be noted that the fetal body weight deficits and retardation in skeletal development (including decreased numbers of caudal vertebral and metacarpal o ssification sites) reported in the oral rat prenatal developmental toxicity study were also evaluated for this acute dietary endpoint. However, it was concluded that such effects are unlikely due to a single dose event and are more appropriate for a repeated exposure scenario. Furthermore, HED has not traditionally considered delays in ossification (and related fetal body

weight deficits) to be single dose effects. Acute Dietary Endpoint ( General population, including infants and children): The current endpoint from the acute neurotoxicity study in rats remains valid for this exposure scenario. Chronic Dietary Endpoint ( All populations): The chronic dietary endpoint is based on fetal body weight deficits and retardation in s keletal development as evidenced b y an increased number of litters with any

variation and a decreased number of caudal vertebral and metacarpal ossificationSulfentrazone Human - Health Risk Assessment DP# 364882

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### sites . This study

provides developmental effects that are likel y due to repeated exposures to sulf entrazone and its NOAEL is the lowest in the databas e . Furthermore, the developmental effects of fetal body

weight deficits and delayed skeletal development at the L OAEL of 25 mg/kg/day

(NOAEL of 10 mg/kg/day) are consistent with those reported in the 2 - g eneration reproductive toxicity

study (see above) at the higher LOAEL of 33 (M) mg/kg/day (NOAEL of 14 mg/kg/day) . In addition, choice of the developmental toxicity study in the rat protects against exposure of women throughout their entire lifespan, which includes their childbearing ye ars. Incidental oral endpoint: The postnatal effects (body weight deficits and survival in both generations) from the 2 - gen. reproduction study remains valid for the incidental oral exposure scenarios. Dermal endpoints: The current endpoint, based on developmental toxicity observed in a dermal developmental toxicity

study in rats, remains valid for the short - and intermediate - term dermal exposure scenarios , for the following reasons: 1) the study is a route - specific study; and 2) developmental toxicity, a primary effect of sulfentrazone via both the oral and dermal routes, was observed in this study in the absence of maternal toxicity . It is also noted that a similar pattern of developmental toxicity (decreased fetal wei ghts, delay s in skeletal ossification) was observed in the dermal developmental toxicity study as in the oral developmental toxicity study . Inhalation endpoints: The short - and intermediate - term inhalation endpoints are based on fetal body weight deficit s and retardation in skeletal development as evidenced by an increased number of litters with any variation and a decreased number of caudal vertebral and metacarpal ossification sites . An oral study was chosen for this exposure scenario in the absence of an inhalation toxicity

study . Assuming 100% absorption via the inhalation route, the oral developmental toxicity

study protects pregnant women who might be exposed via inhalation against the critical effect observed in the sulfentrazone database, develop mental toxicity . Based on the available toxicity database and the Agency's current practices, the inhalation risk for sulfentrazone was assessed using an oral toxicity study . The Agency

sought expert advice and input on issues related to this route to ro ute extrapolation approach (i.e. the use of oral toxicity studies for inhalation risk assessment) from its Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

### ). The Agency is in the process of evaluating the SAP report and may , as appropriate, re - examine and develop new policies and procedures for conducting inhalation risk a ssessments, including route to route extrapolation of toxicity data. If any new policies or procedures are developed, the Agency may revisit the need for an inhalation toxicity

study for sulfentrazone and/or a re - examination of the inhalation toxicity ris k assessment.Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 19 of 58 Table 3.1. Summ ary of Toxicological Doses and Endpoints for Sulfentrazone for Use in Human Health Risk Assessments. Exposure Scenario Point of

Departure Uncertainty/

FQPA Safety Factors RfD, PAD, Level

of Concern for Risk Assessment Study and Relevant Toxicological Effects Acute Dietary (Females 13 - 49) NOAEL = 1 4 mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1X aRfD = aPAD =

0.1 4 mg/kg/day 2 - Gen Reproductive Toxicity Study - Rat

Offspring Toxicity LOAEL= 33 (M) and 40 (F) mg/kg/day ba sed on reduced prenatal viability (fetal & litter), reduced litter size, increased no. of stillborn pups, reduced pup and litter postnatal survival and decreased pup body weights throughout lactation . Acute Dietary (General population including infants an d children) NOAEL = 250 mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1X aRfD =aPAD =

2.5 mg/kg/day Acute -Neurotoxicity Study - Rat

LOAEL = 750 mg/kg/day based on increased incidence of clinical signs and FOB parameters and decreased motor activity. Chronic Di etary (all populations) NOAEL= 1 0 mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1X cRfD = cPAD =

0.1 0 mg/kg/day Prenatal Developmental Toxicity - Rat

Developmental LOAEL = 25 mg/kg/day, based upon decreased mean fetal weights, and retardation in skeletal deve lopment evidenced by an increased number of litters with any variation and by decreased number of caudal vertebral and metacarpal ossification sites. Short - (1 - 30 days) and Intermediate Term (1 - 6 months) Incidental Oral Offspring NOAEL= 14 mg/kg/day UF A = 10X

UF H = 10X FQPA SF = 1X Residential LOC

for MOE = 100 2 - Generation Reproduction Study - Rat

Offspring LOAEL = 33 mg/kg/day based on decreased pup body weights and reduced postnatal survival in both generations. Short - (1 - 30 days), Intermediate - (1 - 6 months), and Long Term (>6 months) Dermal NOAEL= 100 mg/kg/day UF A = 10X

UF H = 10X Residential LOC

for MOE = 100 Occupational LOC for MOE = 100 Dermal Developmental Study - Rat

LOAEL = 250 mg/kg/day based on decreased fetal body weight; increased inci dences of fetal variations: hypoplastic or wavy ribs, incompletely ossified lumbar vertebral arches, and incompletely ossified ischia or pubes; and reduced number of thoracic vertebral and rib ossification sites. Short - (1 - 30 days), Intermediate - (1 - 6 months), and Long Term (>6 months) Inhalation NOAEL= 1 0 mg/kg/day UF A = 10X

UF H = 10X 100% inhalation absorption assumed Residential LOC

for MOE = 100 Occupational LOC for MOE = 100 Prenatal Developmental Toxicity - Rat

Developmental LOAEL = 25 mg/kg/day, b ased upon decreased mean fetal weights, and retardation in skeletal development evidenced by an increased number of litters with any variation and by decreased number of caudal vertebral and metacarpal ossification sites . Cancer (oral, dermal, inhalation) Classification: sulfentrazone is classified as “not likely to be carcinogenic to humans.” NOAEL = no - observed adverse - effect level. LOAEL = lowest - observed adverse - effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (inter species). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF L = extrapolation for use of a LOAEL in the absence of a NOAEL. FQPA SF = FQPA Safety Factor. PAD = population - adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure, LOC = level of concern.Sulfentrazone Human - Health Risk Assessment DP# 364882

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### 3.2 Food Quality Protection Act ( FQ PA) Considerations The RAB1 risk assessment team concluded that the FQPA S afety F actor (SF) can be reduced to 1X for the following reasons :  The toxicity

database for sulfentrazone is complete except for immunotoxicity testing. Recent changes to 40 CFR Part 158 require immunotoxicity testing (OPPTS Guideline 870.7800) for pesticide registration. However, the existing data are sufficient for endpoint selection for exposure/risk assessment scenarios, and for evaluation of the requirements under the FQPA.  The toxicology

database for sulfentrazone does not show any evidence of treatment related effects on the immune system. The overall weight of evidence is consistent with this chemical being a PPO inhibitor resulting in disruption of heme biosynthesis and subsequent effects on on red blood cell dys function (e.g., anemia) . Unlike white blood cells (leukocy

tes) which are cells of the immune sy s tem, red blood cells function to deliver ox ygen to body tissues and are not involved in eliciting an immune response. Furthermore, there is no indication in the sulfentrazone database of any effect on leukocy te counts (an indicator of immune function). Thus, the overall weight of evidence indicates that this chemical does not directl y target the immune system . Sulfentrazone also does not belong to a class of chemicals (e.g., the organotins, heavy m etals, or halogenated aromatic hydrocarbons) that would b e expected to be immunotoxic. An immunotoxicity

study is required as a part of new data requirements in the 40 CFR Part 158 for conventional pesticide registration; however, b ased on the above considerations, EPA does not believe that conducting a functio nal immunotoxicity study will result in a lower point of departure than that currently used for overall risk assessment. Therefore, an additional database UF to account for potential immunotoxicity does not need to be applied.  There is evidence of incre ased quantitative susceptibility following in utero exposure in the oral and dermal developmental toxicity studies in rat and possible evidence of slightly increased qualitative susceptibility of offspring in the 2 - generation rat reproduction study . Howev er, concern is low because clear NOAELs have been identified for the effects noted in these studies and both of the developmental toxicity studies have been chosen for endpoint selection, thereb y protecting the relevant human subpopulations from the noted effects.  The toxicity

database for sulfentrazone does not trigger the need for a developmental neurotoxicity

(DNT) study . There are no indications in any of the studies available that the nervous s ys tem is a target for sulfentrazone. The FOB findings were very non specific signs of toxicity

(perianal staining, colored tears) and motor activity changes only occurred at higher doses following acute exposure, with rapid reversibility, also indicating general toxicity , rather than specific neurotoxicity . The lack of neuropathological findings further supports the non - specific nature of the signs observed . In addition, there is a literature DNT study available for sulfentrazone. The only reliable effects seen in this study involved effects on physical and re flex development, which are known to be affected by body weight. Therefore, these effects are likely secondary to the effects (including body weight deficits) reported in the 2 - generationSulfentrazone Human - Health Risk Assessment DP# 364882

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### reproductive toxicity study. EPA employed an independent statistical method to evaluate the literature DNT in an effort to determine if these effects were consistent with effects observed in other guideline studies at these same dose levels. The results of that analysis indicate that the results of the literature DNT stud y are consistent with what was observed in the rat 2 - generation reproductive study and that the studies used for risk assessment (NOAEL of 10 mg/kg bw/day from the developmental toxicity

study in rat and the NOAEL of 14 mg/kg/day from the 2 generation reproducti on study), are protective of the observations made at ≥25 mg/kg bw/day in the literature study

for which a NOAEL was not attained. Based on the weight of evidence, there is no uncertainty related to developmental neurotoxicity .  The dietary

food exposure a ssessments were performed based on 100 PCT and tolerance level residues . This yields conservative exposure estimates which overstate actual exposure.  The dietary

drinking water assessment utilizes model - generated water concentration values and associated modeling parameters that are designed to provide conservative, health -protective, high - end estimates of water concentrations that will not likely be exceeded.  The residential exposure assessment was conducted using high - end estimates of use and potential exposure providing a conservative, health protective estimate of risk. 3.3 Endocrine Disruption As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally

occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employ s a two - tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal sy stems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal sy stems will proceed to the next stage of the EDSP where EPA will determine which, if any , of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine related effects caused by the substance, and establish a dose - response relationship between the dose and the E, A, or T effect. Between October 2009 and February 2010, EPA issued test orders/data c all - ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. This list of chemicals was selected based on the potential for human exposure through pathways such as food and water, residential activity, and certain post - application agricultural scenarios. This list should not be construed as a list of known or likely endocrine disruptors. Sulfentrazone is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide chemicals. Accordingl y, EPA anticipates issuing future EDSP test orders/data call - ins for all pesticide active ingredients .Sulfentrazone Human - Health Risk Assessment DP# 364882

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### For further information on the status of the EDSP, the po licies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery , please visit our website: http://www.epa.gov/endo/. 3. 4 Recommendation for Aggregate Exposure Risk Assessments For oral exposure, the dietary and drinking water exposures can be combined. For residential exposure, dermal, inhalation , and oral exposures can be aggregated based on a common toxic effects ( changes in body

weight). 4.0 Dietary Exposure/Risk Characterization The assessment of the residue chemistry data submitted in support of the proposed petition was completed on 9 /29/2008 (Memo, W. Wassell, D349321) and an amendment was also completed on 5/28/10 (Memo, W. Wassell, D368179) . The drinking water assessment was completed by EFED on 8/28/08 (Memo, M. Barrett, D349322). The revised dietary exposure assessment is summarized in a pending HED memorandum b y J. L . Van Alstine ( 12/22/10; D384090 ). 4.1 Comparative Metabolic Profile Nature of the Residue in Plants, Livestock, and Rotational Crops Data concerning the metabolism of sulfentrazone in soy beans and confined rotational crops were submitted in conjunction with the petition for use on soy beans (PP#4F04407). Sulfentrazone in plant commodities is metabolized via four different pathway s: (1) Oxidation of the 3 - methyl group to form HMS, followed by further oxidation to form sulfentrazone carbox yl ic acid which is decarbox yl ated to DMS. (2) Hydrol ys is of the trifluoromethyl group to form desdifluoromethyl sulfentrazon e which is oxidized and decarbox yl ated to form desdifluoromethyl desmethylsulfentrazone. (3) Hydrol ys is of the sulfonamide group to form desmethylsulfonyl sulfentrazone. (4) Scission of the phenyl and triazole rings to produce methyltriazole. The corresponding phenyl metabolites are believed to remain bound. The HED Metabolism Committee has determined that the parent compound, sulfentrazone, and the metabolite , HMS , are the residues of concern in soy beans, and that sulfentrazone and the metabolite s HMS and DMS are the residues of concern in rotational crops (D226434, 6/14/96, G. Kramer). In addition, HED concluded that the results of the rotational crop metabolism studies may be translated to support preemergent uses on all ty pes of crops (D220548 , 3/13/96, G. Kramer).Sulfentrazone Human - Health Risk Assessment DP# 364882

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### For the proposed uses of sulfentrazone, limited to preemergence application, the nature of the residue in crops is understood. The residues of concern are sulfentrazone and its metabolites HMS and DMS. However, as the enforcement method for plant commodities determines free and conjugated forms of the anal yt es, the tolerance expression should be revised to indicate the residues of concern are the combined residues of free and conjugated sulfentrazone, and its metabolites HMS and DMS. Additionally, as the proposed directions for use on fruiting vegetables include postemergence applications, HED concludes metabolism data are not available to support the postemergence applications. Adequate ruminant and poultry metabolism studies w ere submitted in conjunction with the soy bean petition (PP#4F04407). The metabolism of sulfentrazone in livestock differs from that in plants as metabolism proceeds onl y b y oxidation of the 3 - methyl group to HMS, followed by further oxidation to form sulf entrazone carbox yl ic acid , which is decarbox yl ated to DMS. Sulfentrazone per se and its metabolites HMS and DMS were identified as the residues of concern in meat, milk, poultry and eggs. The residues of concern in primary crops, rotational crops, livestock, and drinking water are shown in Table 4.1 below. Table 4.1. Residues of Concern in Crops, Livestock, and Drinking Water.

Matrix Tolerance Expression Residues for Risk Assessment Primary Crops sulfentrazone, HMS , DMS (free and conjugated) sulfentrazone, HMS , DMS (free and conjugated) Rotational Crops sulfentrazone, HMS, DMS (free and conjugated) sulfentrazone, HMS, DMS (free and conjugated) Livestock sulfentrazone, HMS, DMS sulfentrazone, HMS, DMS Water Not applicable. sulfentrazone , 3 - carboxyli c acid sulfentrazone 

### 4.2 Drinking Water Residue Profile The previous drinking water exposure assessment for the multiple uses of sulfentrazone can be used in place of a new assessment for the currently proposed multiple uses of Spartan ® 

### 4F (39.6% ai) an d Spartan ® 

### 75DF (75% ai ) (see Memo, L . Lui, 9/15/09, D 366552) . For a complete summary of the drinking water assessments for s ulfentrazone see the EFED memos: R. Parker (4/17/03 ; D284975) and M. Barrett ( 8/28/08 ; D349322). EFED provided Tier 1 estimated drinking water concentrations ( EDWCs ) for groundwater [ using the Screening Concentration In Gro und Water ( SCI - GROW ) model) and surface water [ using the FQPA Index Reservoir Screening Tool ( FIRST ) model ] for sulfentrazone and 3 - carbox yl ic acid sulfentrazone (see Table 4. 2 below). These values generall y represent upper- bound conservative estimates of the total residue concentrations that might be found in surface water and groundwater due to the use of sulfentrazone on sugarcane, cabbage, potatoes, mint or h orseradish. These crops were chosen for this assessment because the label permits use of the maximum application rate (0.375 lb ai/A) and aerial application. Aerial application has the potential for spray drift and is not compatible with soil incorporati on which would reduce surface water concentration values.Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 24 of 58 Table 4.2. Tier 1 EDWCs of Sulfentrazone and 3 - Carboxylic Acid Sulfentrazone in Drinking Water . Chemical Surface Water (ppb ) Groundwater (ppb ) Ac ute Chronic Ac ute and Chronic Sulfentrazone 32. 0 5.1 15.7 3 - Carboxylic Acid Sulfentrazone 3.8 2.7 10.3 Total 35.8 7.8 26.0 

### 4.3 Food Residue Profile Residue Analytical Methods Enforcement method A gas chromatographic (GC) anal ytical method for the determination of free and conjugated residues of s ulfentrazone, DMS, and HMS in/on various matrices was submitted with a petition for a sulfentrazone tolerance on so ybeans (PP# 4F04407). A petition method validation was successfull y completed by the Agency’s Anal ytical Chemistry L aboratory (ACL) . The limit of quantification (LOQ) and limit of detection (L OD) were determined to be 0.05 ppm and 0.005 - 0.025 ppm, respectivel y. HED concluded that the method is suitable for enforcement purposes (D233520, G. Kramer, 3/25/97). The method was forwarded to the F ood and Drug Administration (FDA) for inclusion in the Pesticides Anal ytical Manual, volume II (PAM II, Letter, G. Kramer, 9/18/98). This method is suitable for enforcement of the tolerances associated with this petition. Data - collection methods Samples of raw agricultural commodities (RACS) and processed commodities were anal yz ed for residues of sulfentrazone and its metabolites DMS and HMS using the FMC method entitled, “Anal ytical Methodology for the Determination of Sulfentrazone, 3 - Desmethyl Sulfentr azone, and 3 - Hydrox ym ethylSulfentrazone in/on Various Matrices, Study Number 162MVL 96R1” with minor modifications. Residues in/on broccoli and mustard greens were determined using GC equipped with a halogen - specific detector (XSD), while residues in/on c antaloupe, fruiting vegetables (pepper and tomato), peas, flax, and strawberry were determined using a liquid chromatograph equipped with tandem mass spectrometers (LC/MS/MS) method. The data collection methods described above are adequate based on acceptable method validation and concurrent recovery

data. Multiresidue Method (MRM) MRM data for sulfentrazone and HMS were previously submitted and forwarded to FDA (Memo, 2/7/95, G. Kramer). Neither compound was recovered b y any of the protocols. The FDA PESTDATA database dated 10/99 (PAM Vol. I , Appendix II) indicates that DMS is not recovered using MRM Sections 303 (Mills, Onley, and Gaither; Protocol E, nonfatty) and 304Sulfentrazone Human - Health Risk Assessment DP# 364882

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### (Mills, fatty

food). No information for recovery of DMS using Section 302 (Luke Method; Protocol D) is available. Magnitude of Residues in Plants Vegetable, tuberous and corm, subgroup 1C No new tuberous and corm vegetable field trial data were submitted. An individual tolerance has been established for the combined residues of sulfentrazone and its metabolites HMS and DMS in/on potato at 0.15 ppm [40 CFR §180.498(a)(2)]. Since potato is the representative commodity for the tuberous and corm vegetable, subgroup 1C, IR- 4 is proposing to convert the individual tolerance for potato to a crop subgroup 1C tolerance at the same level. The available potato field trial data (MRID 45582201) were reviewed in conjunction with PP#2E6405. Fourteen potato field trials were conducted in WA (3 trials), ID (2 trials), ME, FL, NC, OH, CO, ND, NJ, NY, and CA at seasonal application rates of 0.375 lb ai/A (1x the maximum proposed seasonal rate) with PHI s of 68 - 158 day s. The maximum combined residues of sulfentrazone and its metabolites HMS and DMS were 0.077 ppm in/on treated potato tubers. Conclusions : The previously submitted residue data for potato are adequate to support the proposed crop subgroup tolerance of 0.15 ppm for residues in/on tuberous and corm vegetables, subgroup 1C. Brassica , head and stem, subgroup 5A Broccoli (47311401.der.doc) Residues of sulfentrazone, DMS, and HMS were each below the LOQ (<0.05 ppm) in/on all samples of broccoli harvested 45 - 73 day s following one broadcast application either to soil 72 hours prior to transplanting or to direct seeded broccoli at the 2 - to 4 - le af growth stage at a rate of 0 .34 - 0.38 lb ai/A; see Table 4.3 .1 . Total sulfentrazone residues were all <0.15 ppm in/on all treated samples of broccoli. Table 4.3 .1 . Summary of Residue Data fromBroccoli Field Trials with Sulfentrazone. Commodity Total Applic.

Rate (lb ai/A) PHI

(days) Residue Levels (ppm)

n Min. Max. HAFT 1 Median Mean Std. Dev. Proposed Use Pattern: Preplant/preemergence application at a maximum rate of 0.375 lb ai/A Sulfentrazone Broccoli 0.34 - 0.38 45 - 73 12 <0.05 <0.05 <0.05 <0 .05 <0.05 -- DMS Broccoli 0.34 - 0.38 45 - 73 12 <0.05 <0.05 <0.05 <0.05 <0.05 -- HMS Broccoli 0.34 - 0.38 45 - 73 12 <0.05 <0.05 <0.05 <0.05 <0.05 -- Total Broccoli 0.34 - 0.38 45 - 73 12 <0.15 <0.15 <0.15 <0.15 <0.15 -- 1 HAFT = highest - average field trial. For calculation of the total residues, HAFT, median, and mean, the LOQ value (<0.05 ppm) was used for all residues reported as below the LOQ.Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 26 of 58 

### Cabbage A tolerance of 0.20 ppm has been established [40 CFR §180.498(a)(2)] for the combined residues of sulfentrazone and its metabolites HMS and DMS in/on cabbage based on residue data reviewed in PP#1E6311. These data indicate that the combined residues of sulfentrazone, HMS, and DMS were <0.15 - 0.18 ppm and <0.15 - 0.17 ppm in/on cabbage he ads with and without wrapper leaves, respectively , harvested 68 - 104 day s following a single ground broadcast application of the 75% DF formulation at 0.375 lb ai/A (1x rate) made 1

- 3 day s prior to transplanting or at the 2 - to 4 - leaf growth stage (33 day s after planting) to direct seeded cabbage. The petition review concluded that two additional cabbage field trials should be conducted in Regions 1 and 8 as a condition for full registration. Conclusions : The submitted residue data for broccoli along with the previously reviewed data for cabbage are adequate to support the proposed crop subgroup tolerance of 0.20 ppm for residues in/on Brassica head and stem, subgroup 5A. Following application of a representative formulation of sulfentrazone at 1x, the c ombined residues of sulfentrazone, DMS, and HMS were <0.15 ppm in/on broccoli, <0.15 - 0.18 ppm in/on cabbage heads with wrapper leaves, and <0.15 - 0.17 ppm in/on cabbage heads without wrapper leaves. As a condition for full registration, HED previously required two additional cabbage field trials to be conducted in Regions 1 and 8. These trials are no longer needed since an adequate number of broccoli and cabbage field trials are available to satisfy geographic representation for head and stem Brassica , sub group 5A. Brassica , leafy

greens, subgroup 5B Mustard Greens (47311402.der.doc) The results of the field trials indicate that residues of sulfentrazone were all below the LOQ (<0.05 ppm) in/on all samples of mustard greens harvested 40 - 66 day s following a preemergence broadcast soil application of a 4 lb/gal FlC formulation of sulfentrazone at a rate of ~0.10 lb ai/A (Treatment Plot 2), ~0.20 lb ai/A (Treatment Plot 3) or ~0.40 lb ai/A (Treatment Plot 4); see Table 4.3 .2 . Maximum residues of DMS were 0 .098 ppm, 0.136 ppm, and <0.05 ppm in/on mustard green samples from Treatment Plots 2, 3, and 4, respectivel y. Maximum residues of HMS were 0.051 ppm, 0.162 ppm, and <0.05 ppm in/on mustard green samples from Treatment Plots 2, 3, and 4, respectively . Maximum total residues were < 0.198 ppm, < 0.291 ppm, and <0.15 ppm in/on mustard green samples from Treatment Plots 2, 3, and 4, respectivel y.Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 27 of 58 Table 4.3 .2 . Summary of Residue Data fromMustard Green Field Trials with Sulfentrazone. Commodity PHI

(days) Trt

Pl ot No. Total Applic. Rate (lb ai/A) Residue Levels (ppm)

n Min. Max. HAFT 1 Median Mean Std. Dev. Proposed Use Pattern: Preplant/preemergence application at a maximum rate of 0.375 lb ai/A Sulfentrazone Mustard greens, leaves 40 - 66 2 0.092 - 0.10 8 14 <0.05 <0.05 <0.05 <0.05 <0.05 -- 3 0.199 - 0.222 14 <0.05 <0.05 <0.05 <0.05 <0.05 -- 4 0.402 2 <0.05 <0.05 <0.05 <0.05 <0.05 -- DMS Mustard greens, leaves 40 - 66 2 0.092 - 0.108 14 <0.05 0.098 0.074 <0.05 0.053 0.013 3 0.199 - 0.222 14 <0.05 0.136 0.109 <0.05 0.058 0.024 4 0.402 2 <0.05 <0.05 <0.05 <0.05 <0.05 -- HMS Mustard greens, leaves 40 - 66 2 0.092 - 0.108 14 <0.05 0.051 0.051 <0.05 <0.050 0.000 3 0.199 - 0.222 14 <0.05 0.162 0.148 <0.05 0.070 0.037 4 0.402 2 <0.05 <0.05 < 0.05 <0.05 <0. 05 -- Total Mustard greens, leaves 40 - 66 2 0.092 - 0.108 14 <0.15 <0.198 0.174 <0.15 0.154 0.013 3 0.199 - 0.222 14 <0.15 <0.291 0.248 <0.15 0.178 0.049 4 0.402 2 <0.15 <0.15 <0.15 <0.15 <0.15 -- 1 HAFT = highest - average field trial. For calculation of the total residues, HAFT, median, and mean, the LOQ value (<0.05 ppm) was used for all residues reported as below the LOQ. 

### Conclusions : The submitted residue data for mustard greens, which is the representative commodity

of Brassica leafy

greens, sub group 5B, are adequate to fulfill data requirements provided the use directions are revised to indicate a maximum single and seasonal application rate of 0.20 lb ai/A. The number and locations of crop field trials are in accordance with OPPTS Guideline 86 0.1500 and the trials conducted reflect the revised proposed use pattern. The residue data for mustard greens indicate that total residues were <0.15 ppm in/on two samples treated at 0.402 lb ai/A (~1.1x). It is noted that higher residues were observed o n samples treated at <1.0x. Maximum total residues of <0.198 ppm and <0.291 ppm were reported in/on samples treated at ~0.3x and ~0.5x. The residue data for mustard greens were not entered into the Agency ’s tolerance spreadsheet as specified by the Guida nce for Setting Pesticide Tolerances Based on Field Trial Data SOP to determine the tolerance level as more than half of the samples (8 of 14) had residues that were less then the LOQ (0.05 ppm). HED concludes the data support a tolerance level of 0.40 pp m for free and conjugated residues of sulfentrazone, HMS , and DMS in/on Brassica leafy

greens, subgroup 5B. A revised Section F is required. Vegetable, Legume, Group 6 Pea, succulent (47311406.der.doc) The results of the field trials show that residue s of sulfentrazone, DMS, and HMS were each below the LOQ (<0.05 ppm) in/on samples of peas ( succulent shelled and edible - podded) harvested 52 - 168 days after a single preemergence broadcast application of a 75% DFSulfentrazone Human - Health Risk Assessment DP# 364882

Page 28 of 58 

### formulation of sulfentrazone made to soil at target rates of ~0.1875 lb ai/A (1x; Treatment Plot 2) or ~0.25 lb ai/A (1.3x; Treatment Plot 3); see Table 4.3 .3 . Total sulfentrazone residues were <0.15 ppm in/on all treated samples of succulent shelled and edible - podded peas. Table 4.3 .3 . Summary of Residue Data fromSucculent Pea Field Trials with Sulfentrazone. Commodity PHI

(days) Trt

No. Total Applic. Rate (lb ai/A) Residue Levels (ppm)

n Min. Max. HAFT Median Mean Std. Dev. Proposed Use Pattern: Preemergence application at a maximum rate of 0.1875 lb ai/A Sulfentrazone Pea, succulent shelled and edible - podded 52 - 168 2 0.181 - 0.198 22 <0.05 <0.05 <0.05 <0.05 <0.05 -- 3 0.242 - 0.264 22 <0.05 <0.05 <0.05 <0.05 <0.05 -- DMS Pea, succulent shelled and edible - podded 52 - 168 2 0.181 - 0.198 22 <0.05 <0.05 <0.05 <0.05 <0.05 -- 3 0.242 - 0.264 22 <0.05 <0.05 <0.05 <0.05 <0.05 -- HMS Pea, succulent shelled and edible - podded 52 - 168 2 0.181 - 0.198 22 <0.05 <0.05 <0.05 <0.05 <0.05 -- 3 0.242 - 0.264 22 <0.05 <0.05 <0.05 <0.05 <0.05 -- Total P ea, succulent shelled and edible - podded 52 - 168 2 0.181 - 0.198 22 <0.15 <0.15 <0.15 <0.15 <0.15 -- 3 0.242 - 0.264 22 <0.15 <0.15 <0.15 <0.15 <0.15 -- 1 HAFT = highest - average field trial. For calculation of the total residues, HAFT, median, and mean, th e LOQ value (<0.05 ppm) was used for all residues reported as below the LOQ. 

### Conclusions : The submitted residue data for succulent peas are adequate to fulfill data requirements. The number and locations of crop field trials are in accordance with OPPTS Guideline 860.1500, and the trials conducted reflect the proposed use pattern. The field trial data will support a tolerance of 0.15 ppm for residues in/on succulent peas. The combined residues of sulfentrazone, DMS, and HMS were <0.15 ppm in/on mature peas ( succulent shelled and edible podded) following treatment according to the proposed use pattern. A revised Section F is required since the petitioner has proposed a tolerance level of 0.05 ppm for residues in/on mature peas ( succulent shelled and edible -podded). Vegetable, fruiting, group 8 Tomato and Peppers: (47311404.der.doc (includes MRID 47311405)) The crop field studies show that residues of sulfentrazone, DMS, and HMS were each <LOQ (<0.05 ppm) in/on all samples of peppers and tomatoes harvested 19 - 22 day s following the last of two applications (a soil surface, pre - transplant, banded application followed by a postemergence application made between rows with a shielded/hooded sprayer) of either a 4 lb/gal FlC formulation or a 75% DF formulation of sulfentrazone, at total rates of 0.40 lb ai/A (1.1x), 0.50 lb ai/A (1.3x), and 0.7 5 lb ai/A (2.0x); see Table 4.3 .4 . Total combined residues ofSulfentrazone Human - Health Risk Assessment DP# 364882

Page 29 of 58 

### sulfentrazone, DMS, and HMS were all <0.15 ppm in/on all treated samples of peppers and tomatoes. Ta ble 4.3 .4 . Summary of Residue Data fromFruiting Vegetable Field Trials with Sulfentrazone. Commodity PHI

(days) Trt

Pl ot No. Total Applic. Rate (lb ai/A) Residue Levels (ppm)

n Min. Max. HAFT 1 Median Mean Std. Dev. Proposed Use Pattern: Preplant or postemergence application at a maximum seasonal rate of 0.375 lb ai/A Sulfentrazone Bell Pepper 19 - 21 2 0.505 - 0.512 12 <0.05 <0.05 <0.05 <0.05 <0.05 -- 3 0.739 - 0.773 12 <0.05 <0.05 <0.05 <0.05 <0.05 -- 21 4 0.410 2 <0.05 <0.05 <0.05 <0.05 <0.05 --

5 0.504 - 0.507 4 <0.05 <0.05 <0.05 <0.05 <0.05 -- 6 0.758 - 0.779 4 <0.05 <0.05 <0.05 <0.05 <0.05 -- Non - bell pepper 19 - 22 2 0.499 - 0.505 8 <0.05 <0.05 <0.05 <0.05 <0.05 -- 3 0.750 - 0.761 8 <0.05 <0.05 <0.05 <0.05 <0.05 -- To mato 19 - 21 2 0.489 - 1. 004 28 <0.05 <0.05 <0.05 <0.05 <0.05 -- 3 0.730 - 0.982 28 <0.05 <0.05 <0.05 <0.05 <0.05 -- 21 4 0.537 2 <0.05 <0.05 <0.05 <0.05 <0.05 -- 19 - 21 5 0.490 - 0.504 4 <0.05 <0.05 <0.05 <0.05 <0.05 --

6 0.739 - 0.758 4 <0.05 <0.05 <0.05 <0.05 <0.05 -- DMS Bell Pepper 19 - 21 2 0.505 - 0.512 12 <0.05 <0.05 <0.05 <0.05 <0.05 -- 3 0.739 - 0.773 12 <0.05 <0.05 <0.05 <0.05 <0.05 -- 21 4 0.410 2 <0.05 <0.05 <0.05 <0.05 <0.05 --

5 0.504 - 0.507 4 <0.05 <0.05 <0.05 <0.05 <0.05 -- 6 0.758 - 0.779 4 <0.05 <0.05 <0.0 5 <0.05 <0.05 -- Non - bell pepper 19 - 22 2 0.499 - 0.505 8 <0.05 <0.05 <0.05 <0.05 <0.05 -- 3 0.750 - 0.761 8 <0.05 <0.05 <0.05 <0.05 <0.05 -- To mato 19 - 21 2 0.489 - 1.004 28 <0.05 <0.05 <0.05 <0.05 <0.05 -- 3 0.730 - 0.982 28 <0.05 <0.05 <0.05 <0.05 <0.05 - - 21 4 0.537 2 <0.05 <0.05 <0.05 <0.05 <0.05 -- 19 - 21 5 0.490 - 0.504 4 <0.05 <0.05 <0.05 <0.05 <0.05 --

6 0.739 - 0.758 4 <0.05 <0.05 <0.05 <0.05 <0.05 -- HMS Bell Pepper 19 - 21 2 0.505 - 0.512 12 <0.05 <0.05 <0.05 <0.05 <0.05 -- 3 0.739 - 0.773 12 <0. 05 <0.05 <0.05 <0.05 <0.05 -- 21 4 0.410 2 <0.05 <0.05 <0.05 <0.05 <0.05 --

5 0.504 - 0.507 4 <0.05 <0.05 <0.05 <0.05 <0.05 -- 6 0.758 - 0.779 4 <0.05 <0.05 <0.05 <0.05 <0.05 -- Non - bell pepper 19 - 22 2 0.499 - 0.505 8 <0.05 <0.05 <0.05 <0.05 <0.05 -- 3 0.750 - 0.761 8 <0.05 <0.05 <0.05 <0.05 <0.05 -- To mato 19 - 21 2 0.489 - 1.004 28 <0.05 <0.05 <0.05 <0.05 <0.05 -- 3 0.730 - 0.982 28 <0.05 <0.05 <0.05 <0.05 <0.05 -- 21 4 0.537 2 <0.05 <0.05 <0.05 <0.05 <0.05 -- 19 - 21 5 0.490 - 0.504 4 <0.05 <0.05 <0.05 <0.05 <0.05 --

6 0.739 - 0.758 4 <0.05 <0.05 <0.05 <0.05 <0.05 -- TotalSulfentrazone Human - Health Risk Assessment DP# 364882

Page 30 of 58 Ta ble 4.3 .4 . Summary of Residue Data fromFruiting Vegetable Field Trials with Sulfentrazone. Commodity PHI

(days) Trt

Pl ot No. Total Applic. Rate (lb ai/A) Residue Levels (ppm)

n Min. Max. HAFT 1 Median Mean Std. Dev. Bell Pepper 19 - 21 2 0.505 - 0.512 12 <0.15 <0.15 <0.15 <0.15 <0.15 -- 3 0.739 - 0.773 12 <0.15 <0.15 <0.15 <0.15 <0.15 -- 21 4 0.410 2 <0.15 <0.15 <0.15 <0.15 <0.15 --

5 0.504 - 0.507 4 <0.15 <0.15 <0.15 <0.15 <0.15 -- 6 0.758 - 0.779 4 <0.15 <0.15 <0.15 <0.15 <0.15 -- Non - bell pepper 19 - 22 2 0.499 - 0.505 8 <0.15 <0.15 <0.15 <0.15 <0.15 -- 3 0.750 - 0.761 8 <0.15 <0.15 <0.15 <0.15 <0.15 -- To mato 19 - 21 2 0.489 - 1.004 28 <0.15 <0 .15 <0.15 <0.15 <0.15 -- 3 0.730 - 0.982 28 <0.15 <0.15 <0.15 <0.15 <0.15 -- 21 4 0.537 2 <0.15 <0.15 <0.15 <0.15 <0.15 -- 19 - 21 5 0.490 - 0.504 4 <0.15 <0.15 <0.15 <0.15 <0.15 --

6 0.739 - 0.758 4 <0.15 <0.15 <0.15 <0.15 <0.15 -- 1 HAFT = highest - av erage field trial. For calculation of the total residues, HAFT, median, and mean, the LOQ value (<0.05 ppm) was used for all residues reported as below the LOQ. 

### Conclusions : The submitted residue data for peppers (bell and non - bell) and tomatoes are ade quate. The number and locations of crop field trials are in accordance with OPPTS Guideline 860.1500 and the trials conducted reflect the proposed use pattern. The field trial data will support a tolerance of 0.15 ppm for residues in/on fruiting vegetabl es, crop group 8. Following two applications (a soil surface, pre - transplant, banded application followed by a postemergence application made between rows with a shielded/hooded sprayer) of representative formulations at ~1.1 - 2.0x, the combined residues o f sulfentrazone, DMS, and HMS were <0.15 ppm in/on the representative commodities. A revised Section B is required to remove postemergence uses on the labels since metabolism data are not available to support this use pattern. A revised Section F is also required since the petitioner has proposed a crop group tolerance level of 0.05 ppm. Okra Okra residue data were not submitted in support of the proposed use on okra. IR - 4 has proposed to translate the existing and submitted fruiting vegetable data (p eppers and tomatoes) to okra. The proposed use on okra is identical to the proposed use on the fruiting vegetables crop group. HED has approved adding okra to the fruiting vegetable crop group (see minutes of ChemSAC meeting of 10/18/06). Until 40 CFR § 180.41 is updated, a separate tolerance must be established for residues in/on okra. Conclusions : The available data for the fruiting vegetables, crop group 8 may be used to support the proposed tolerance for residues in/on okra. The tolerance should be established at the same level (0.15 ppm) as the fruiting vegetable group tolerance.Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 31 of 58 

### Melon subgroup 9A : (47311403.der.doc) The results of the field trials indicate that residues of sulfentrazone, DMS, and HMS were below the L OQ (<0.05 ppm) in/on all samples of cantaloupe harvested 59 - 94 day s after a single broadcast application of a 75% DF formulation of sulfentrazone to soil surface at pre - transplant or preemergence at rates of ~0.20 lb ai/A (Treatment Plot 2), ~0.25 lb ai/A (Treatment Plot 3) or ~0.15 lb ai/A (Treatment Plot 4), with one exception. In one CA trial, residues of HMS were 0.052 ppm in/on cantaloupe samples from Treatment Plot 2. Maximum total residues were <0.152 ppm, <0.15 ppm, and <0.15 ppm in/on cantaloupes from Treatment Plots 2, 3, and 4, respectivel y. The results of these field tri als are summarized in Table 4.3 .5 . Table 4.3 .5 . Summary of Residue Data fromCantaloupe Field Trials with Sulfentrazone. Commodity PHI

(days) Trt

No. Total Applic. Rate (lb ai/A) Residue Levels (pp m)

n Min. Max. HAFT 1 Median Mean Std. Dev. Proposed Use Pattern: Preemergence application at a maximum seasonal rate of 0.25 lb ai/A Sulfentrazone Cantaloupe, fruit 59 - 94 2 0.20 - 0.22 16 <0.05 <0.05 <0.05 <0.05 <0.05 -- 3 0.25 - 0.27 16 <0.05 <0.0 5 <0.05 <0.05 <0.05 -- 4 0.16 2 <0.05 <0.05 <0.05 <0.05 <0.05 -- DMS Cantaloupe, fruit 59 - 94 2 0.20 - 0.22 16 <0.05 <0.05 <0.05 <0.05 <0.05 -- 3 0.25 - 0.27 16 <0.05 <0.05 <0.05 <0.05 <0.05 -- 4 0.16 2 <0.05 <0.05 <0.05 <0.05 <0.05 -- HMS Cantalou pe, fruit 59 - 94 2 0.20 - 0.22 16 <0.05 0.052 0.051 <0.05 <0.05 -- 3 0.25 - 0.27 16 <0.05 <0.05 <0.05 <0.05 <0.05 -- 4 0.16 2 <0.05 <0.05 <0.05 <0.05 <0.05 -- Total Cantaloupe, fruit 59 - 94 2 0.20 - 0.22 16 <0.15 <0.152 <0.151 <0.15 <0.15 -- 3 0.25 - 0.27 16 <0.15 <0.15 <0.15 <0.15 <0.15 -- 4 0.16 2 <0.15 <0.15 <0.15 <0.15 <0.15 -- 1 HAFT = highest - average field trial. For calculation of the total residues, HAFT, median, and mean, the LOQ value (<0.05 ppm) was used for all residues reported as below the LOQ. 

### Conclusion s: The submitted residue data for cantaloupes are adequate to support a tolerance of 0.15 ppm for residues in/on the melon subgroup 9A. The number and locations of crop field trials are in accordance with OPPTS Guideline 860.1500, and the trials conducted reflect the proposed use pattern. Following pre - transplant or preemergence application of a representative formulation at ~0.6 - 1.0x, the combined residues of sulfentrazone, DMS, and HMS were <0.15 ppm in/on mature cantaloupes. A rev ised Section F is required since the petitioner has proposed a crop subgroup tolerance level of 0.10 ppm.Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 32 of 58 

### Strawberry (47311408.der.doc) The results of the field trials show that residues of sulfentrazone, DMS, and HMS were each <LOQ (0.05 ppm) in/on all samples of strawberry harvested 56 - 189 day s following a single broadcast soil application of a 75% DF formulation of sulfentrazone made preplant (annual strawberry

crops) or during the dormant phase (perennial strawberry crops) at a rate of 0.25 - 0.26 lb ai/A (Treatment Plot 2) or 0.38 - 0.40 lb ai/A (T reatment Plot 3); see Table 4.3 .6 . Total sulfentrazone residues were <0.15 ppm in/on all treated samples of strawberry . Table 4.3 .6 . Summary of Residue Data fromStrawberry Field Trials with Sulfentrazone. C ommodity Total Applic.

Rate (lb ai/A) PHI

(days) Residue Levels (ppm)

n Min. Max. HAFT 1 Median Mean Std. Dev. Proposed Use Pattern: Preemergence application at a maximum seasonal rate of 0.25 lb ai/A Sulfentrazone Strawberry 0.25 - 0.26 56 - 189 16 <0 .05 <0.05 <0.05 <0.05 <0.05 --

0.38 - 0.40 16 <0.05 <0.05 <0.05 <0.05 <0.05 -- DMS Strawberry 0.25 - 0.26 56 - 189 16 <0.05 <0.05 <0.05 <0.05 <0.05 --

0.38 - 0.40 16 <0.05 <0.05 <0.05 <0.05 <0.05 -- HMS Strawberry 0.25 - 0.26 56 - 189 16 <0.05 <0.05 0.05 0.0 5 <0.05 --

0.38 - 0.40 16 <0.05 <0.05 0.05 0.05 <0.05 -- Total Strawberry 0.25 - 0.26 56 - 189 16 <0.15 <0.15 <0.15 <0.15 <0.15 --

0.38 - 0.40 16 <0.15 <0.15 <0.15 <0.15 <0.15 -- 1 HAFT = highest - average field trial. For calculation of the total residue s, HAFT, median, and mean, the LOQ value (<0.05 ppm) was used for all residues reported as below the LOQ. 

### Conclusions : The submitted residue data for strawberries are adequate to fulfill data requirements. The number and locations of crop field trials are in accordance with OPPTS Guideline 860.1500, and the trials conducted reflect the proposed use pattern. The field trial data support a tolerance of 0.15 ppm for residues in/on strawberry . The combined residues of sulfentrazone, DMS, and HMS were <0.15 ppm in/on mature strawberries following a pre - plant or dormant application of a representative sulfentrazone formulation at 1.0 - 1.6x. A revised Section F is required since the petitioner has proposed a tolerance level of 0.05 ppm for residues in/on strawberries. Flax: (47311407.de1.doc) The results of the field trials indicate that residues of sulfentrazone, DMS, and HMS were each <LOQ (0.05 ppm) in/on all samples of flax seed harvested 111 - 123 day s after a single preemergence broadcast soil applicatio n of a 75% DF formulation or mixture of two 75% DF formulations of sulfentrazone at a rate o f ~0.375 lb ai/A; see Table 4.3 .7 . Total sulfentrazone residues were <0.15 ppm in/on all treated samples of flax seed.Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 33 of 58 Table 4.3 .7 . Summary of Residue Data fro m Flax Field Trials with Sulfentrazone. Commodity Total Applic.

Rate (lb ai/A) PHI

(days) Residue Levels (ppm)

n Min. Max. HAFT 1 Median Mean Std. Dev. Proposed Use Pattern: Preemergence application at a maximum seasonal rate of 0.375 lb ai/A Sulfe ntrazone Flax, seed 0.365 - 0.383 111 - 123 12 <0.05 <0.05 <0.05 <0.05 <0.05 -- DMS Flax, seed 0.365 - 0.383 111 - 123 12 <0.05 <0.05 <0.05 <0.05 <0.05 -- HMS Flax, seed 0.365 - 0.383 111 - 123 12 <0.05 <0.05 <0.05 <0.05 <0.05 -- Total Flax, seed 0.365 - 0.383 11 1 - 123 12 <0.15 <0.15 <0.15 <0.15 <0.15 -- 1 HAFT = highest - average field trial. For calculation of the total residues, HAFT, median, and mean, the LOQ value (<0.05 ppm) was used for all residues reported as below the LOQ. 

### Conclusions : The submitted re sidue data for flax are adequate to fulfill the data requirements. The number and locations of crop field trials are in accordance with OPPTS Guideline 860.1500, and the trials conducted reflect the proposed use pattern. The field trial data will support a tolerance of 0.15 ppm for residues in/on flax seed. The combined residues of sulfentrazone, DMS, and HMS were <0.15 ppm in/on flax seed following a preemergence application of a representative sulfentrazone formulation at 1.0x. A revised Section F is required since the petitioner has proposed a tolerance for residues in/on flax seed at 0.05 ppm. A summary

of proposed and recommended tolerances for sulfentrazone is presented in Table 4.3 .8 . Table 4.3 .8 . Tolerance Summary for Sulfentrazone. Commodity Proposed Tolerance (ppm) Recommended

Tolerance (ppm) Comments Brassica , head and stem, subgroup 5A 0.20 0.20 The established tolerance for cabbage under 180.498(a)(2) should be removed concomitantly when the subgroup 5A tolerance is established Brassic a , leafy greens, subgroup 5B 0.35 0.40 Melon subgroup 9A 0.10 0.15 Vegetable, fruiting, group 8 0.05 0.15 Okra 0.05 0.15 Pea, succulent 0.05 0.15 Flax , seed 0.05 0.15 The established time - limited tolerance for flax seed under 180.498(b) should be removed concomitantly when the permanent flax tolerance is established.Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 34 of 58 Table 4.3 .8 . Tolerance Summary for Sulfentrazone. Commodity Proposed Tolerance (ppm) Recommended

Tolerance (ppm) Comments Straw berry 0.05 0.15 The established time - limited tolerance for straw

berry under 180.498(b) should be removed concomitantly when the permanent straw berry tolerance is established. V egetable, tuberous and corm, subgroup 1C 0.15 0.15 Tolerance recommendation is based on residue data translated from potato. The established tolerance for potato under 180.498(a)(2) should be removed concomitantly when the subgroup 1C tolerance is establi shed. Cocona 0.15 0.15 Eggplant, African 0.15 0.15 Eggplant, pea 0.15 0.15 Eggplant, scarlet 0.15 0.15 Goji berry 0.15 0.15 Huckleberry, garden 0.15 0.15 Martynia 0.15 0.15 Naranjilla 0.15 0.15 Okra 0.15 0.15 Roselle 0.15 0.15 Sunberry 0.15 0.15 Tomato, bush 0.15 0.15 Tomato, currant 0.15 0.15 Tomato, tree 0.15 0.15 

### Magnitude of Residues in Livestock Adequate ruminant and poultry metabolism studies were submitted in conjunction with the soy bean petition (PP#4F04407). The metabolism of sulfentrazone in livestock differs from that in plants as metabolism proceeds onl y b y oxidation of the 3 - methyl group to form HMS, followed b y further oxidation to form sulfentrazone carboxyl ic acid which is decarbox yl ated to DMS. Sulfentrazone per se and its metabolites HMS and DMS were identified as the residues of concern in meat, milk, poultry and eggs. HED previousl y determined that, based on the established sulfentrazone tolerances for so ybean and cereal grain commodities and the results of the livestock metabolism studies, conventional feeding studies are not required. This conclusion was reevaluated in conjunction with PP#s 2F6391 and 2E6405 ( 

### D287102, 1/10/03, G. Kramer) based on revised dietary burdens resulting from a diet comp rised of corn and potato commodities for beef and dairy cattle and corn and rice commodities for poultry . Since a dietary exposure of 10x would not result in quantifiable residues, HED concluded that conventional ruminant and poultry feeding studies were still not required.Sulfentrazone Human - Health Risk Assessment DP# 364882

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### In the current petition, the only livestock feedstuff is flax meal. Flax meal is a feed commodity for cattle and swine (10% of diet) and poultry (30% of diet), but would contribute a minor percentage to livestock diets compared to so y beans and cereal grains. Residues of sulfentrazone and its metabolites in/on flax will not result in a higher dietary burden, and tolerances for residues in/on meat, milk, poultry , and egg are not required to support preemergence uses on flax. Storage Stability The available storage stability data for sulfentrazone are adequate to support the storage conditions and durations of samples of Brassica , h ead and s tem [ broccoli, Chinese broccoli, Brussels sprouts, Chinese (napa) cabbage, Chinese mustard, cauli flower, cavalo broccoli, kohlrabi ]; Brassica , l eafy greens [ broccoli raab, Chinese (bok cho y) cabbage, collards, kale, mizuna, mustard greens, mustard spinach, rape greens ]; f ruiting v egetables (except curcurbits) [eggplant, groundcherry (Physalis spp), pepino, pepper (includes bell pepper, chili pepper, cooking pepper, pimento, sweet pepper), tomatillo, tomato]; okra ; s ucculent p eas and b eans [bean (Phaseolus; includes green lima bean and succulent broad bean), bean ( Vigna ; includes blackeyed pea, cowpea, southern pea), pea ( Pisum ; includes Engl ish pea, garden pea, green pea), pigeon pea; flax; melon ( citron melon, muskmelon, watermelon) ; and strawberry from the submitted crop field trials and the flax and tomato processing studies. There are no storage st ability issues and no corrections for storage stability need be applied to the field trial and processing studies. Processed Food/Feed Flax 47311407.de2.doc IR- 4 has submitted processing data for sulfentrazone on flax. Inone trial conducted in ND during the 2002 growing season, flax seed was harvested 123 day s following a single preemergence broadcast soil application of a 75% DF formulation of sulfentrazone at a rate of 0.3718 lb ai/A (~1x), without an adjuvant. The harvested flax seeds were process ed into meal and oil using simulated commercial processing procedures. The processing study indicates that all residues of sulfentrazone, DMS, and HMS were <LOQ (0.05 ppm) in flax seed (RAC), meal, and oil. Since all residues were <LOQ, processing factors could not be calculated. IR - 4 decided to forego 5x exaggerated studies due to concerns of phy totoxicity, and uncertainty concerning producing commodities with quantifiable residues. HED concludes that an additional flax processing study is not required . Tomato 47311405.der.doc IR- 4 has submitted the results of a tomato processing study with sulfentrazone. Samples used for processing were generated from a field trial conducted in CA during the 2004 growing season. Tomatoes were harvested 20 days fol lowing two applications ( one banded application to soilSulfentrazone Human - Health Risk Assessment DP# 364882

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### surface pre - transplant and one postemergence application between rows using a shielded/hooded sprayer) of a 4 lb/gal FlC formulation of sulfentrazone, applied at rates of ~0.250 lb ai/A/application, f

or a total rate of ~0.500 lb ai/A (~1.3x; Treatment Plot 2) or at ~0.375 lb ai/A/application, for a total rate of ~0.750 lb ai/A (2.0x; Treatment Plot 3). Applications were made at a 99 - day

retreatment interval, in 25 - 31 GPA spray volumes, without an adjuvant. The collected tomato samples were processed into paste and puree using simulated commercial procedures. The processing study indicates that all residues of sulfentrazone, DMS, and HMS were <LOQ (<0.05 ppm) in/on tomato fruit, paste, and puree. Sin ce all residues were <LOQ, processing factors could not be calculated. The study reported that phytotoxic effects occurred after the first application but the crops fully recovered b y the second application. The maximum theoretical concentration factors are 5.5x for processing to tomato paste (OPPTS 860.1520, Table 1). IR- 4 decided to forego 5x exaggerated studies due to concerns of phy totoxicity , delayed fruit set, and uncertainty

concerning producing commodities with quantifiable residues. HED concludes an additional tomato processing study is not required. Field Accumulation in Rotational Crops Rotational crop studies for corn, rice, sorghum, and wheat were previously submitted in conjunction with the soybean petition (PP#4F04407). Permanent tolerances have been established for indirect or inadvertent residues of sulfentrazone and its metabolites, HMS and DMS, in cereal grains (excluding sweet corn), bran, forage, grain, hay, hulls, stover, and straw as a result of the use on so ybeans. As the 1x u se rate in soy beans (0.375 lb ai/A) is ≥ the 1x use rate of the proposed new uses, the established tolerances for indirect or inadvertent residues of sulfentrazone and its metabolites, HMS and DMS are adequate to support the subject petition. The proposed rotational crop restrictions are adequate and consistent with previous sulfentrazone petitions. 4.4 International Residue Limits No Codex, Canadian, or Mexican maximum residue limits ( MRL s ) have been established for sulfentrazone on the subject crops; therefore, harmonization of MRL s and U.S. tolerances is not an issue at this time. 4. 5 Dietary Exposure Analyses The revised dietary

exposure assessment is summarized in the HED memorandum by J. L . Van Alstine ( 12/22/10; D384090 ). Acute and chronic anal y ses were performed using DEEM - FCID TM 

### (ver. 2.03). DEEM - FCID TM 

### (ver. 2.03) estimates the dietary exposure of the U.S. population and various population subgroups. The results reported are for the general U.S. Population, all infants (<1 ye ar old), children 1 - 2 years old, children 3 - 5 years old, children 6 - 12 years old, youth 13 - 19 years old, females 13 - 49 years old, adults 20 - 49 years old, and adults 50+ years old.Sulfentrazone Human - Health Risk Assessment DP# 364882

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### The acute and chronic analy se s assumed tolerance - level residues for all commodities, 100% CT, and DEEM  

### (ver. 7.81) default p rocessing factors (as necessary) . The analys e s also incorporated the drinking water estimates provided by EFED. The EDWCs w ere Tier 1 estimates for groundwater using the SCI - GROW model and surface water using the FIRST model for sulfentrazone and 3 - carbo xylic acid sulfentrazone. The models utilized an application rate of 0.375 lb ai/A with 2 applications per season. EDWCs of 0.0358 ppm and 0.026 ppm were used in the acute and chronic anal ys is, respectively . The resulting acute food plus water risk es timates are below HED ’s level of concern [<100% of the aPAD] at the 95 th 

### percentile of the exposure distribution for the U.S. general population ( less than 1 .0 % aPAD), and all population subgroups . The aPAD is lower for females 13 - 49 years old . The population subgroup with the greatest risk was females 13 - 49 years old which utilized less than 3 .0 % of the aPAD. See Table 4.5.1 below for a summary of the results of the acute assessment. The resulting chronic risk estimates are be low HED’s level of concern. The most highl y exposed population subgroup was children 1 - 2 years old , which utilized less than 4 .0 % of the cPAD. See Table 4 .5.2 below for a summary of the results of the chronic assessment. Table Table 4.5.1. Summ ary o f Acute Dietary Exposure and Risk for Sulfentrazone at the 95 th Percentile. 1 Population Subgroup aPAD (m g/kg/day) Exposure (mg/kg/day) %aPAD General U.S. Population

2.5 0.004347 <1.0 All Infants (< 1 year old) 0.009388 <1.0 Children 1 - 2 ye ars old 0.008187 <1.0 Children 3 - 5 years old 0.007476 <1.0 Children 6 - 12 years old 0.005284 <1.0 Youth 13 - 19 years old 0.003695 <1.0 Adults 20 - 49 years old 0.003341 <1.0 Adults 50+ years old 0.002942 <1.0 Fem ales 1 3 - 49 years old 0.14 0.003256 2.3 1 The population with the greatest risk is bolded. Table 4.5.2. Summary of Chronic Dietary Exposure and Risk for Sulfentrazone. 1 Population Subgroup cPAD (m g/kg/day) Exposure (mg/kg/day) %cPAD General U.S. Population

0 .10 0.001751 1.8 All Infants (< 1 year old) 0.003117 3.1 Children 1 - 2 years old 0.003565 3.6 Children 3 - 5 years old 0.003463 3.5 Children 6 - 12 years old 0.002404 2 .4 Youth 13 - 19 years old 0.001660 1.7 Adults 20 - 49 years old 0.001492 1.5 Adults 50+ years old 0.001360 1.4 Females 13 - 49 years old 0.001451 1.5Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 38 of 58 1 The population with the greatest risk is bolded. 

### 5.0 Residential (Non - Occupational) Exposure/Risk Pathway There are no proposed residential uses at this time; however, there is an existing residential turf use that was assessed previously ( D 289349 , M. Dow, 15 - May- 2003 ) . Since that asse ssment, there has been communication between the Registrant and EPA regarding the maximum rates allowed on the labels for the residential use sites. Based on this communication, a maximum rate of 0.375 lb ai/A has been identified and all registered sulfentrazone labels with residential turf uses will be revised to reflect this maximum rate. Therefore, a revised residential handler and postapplication assessment is included here. The revised residential exposure and risk assessment is summarized in the pending HED memorandum b y K. Lowe ( D 364913 ). 5.1 Residential Handler Exposure Assessing exposures and risks resulting from residential uses is very similar to assessing occupational exposures and risks, with the following exceptions:

 Residential handler expo sure scenarios are considered to be short - term only , due to the infrequent use patterns associated with homeowner products.

 A tiered approach for personal protection using increasing levels of personal protective equipment (PPE ) is not used in residential handler risk assessments. Homeowner handler assessments are based on the assumption that individuals are wearing shorts, shortsleeved shirts, socks, and shoes.

 Homeowner handlers are expected to complete all tasks associated with the use of a pesticide product including mixing/loading if needed as well as the application. It has been determined that exposure to pesticide handlers is likely during the residential use of sulfentrazone on residential lawns. The quantitative exposure/risk assessment devel oped for residential handlers is based on the following scenarios: Mixer/Loader/Applicators (1) Mixing/Loading/Applying Liquids with Low - Pressure Handwand (PHED), (2) Mixing/Loading/Applying Liquids with Hose - End Sprayer (Residential ORETF data; MRID 449722 - 0 1; OMA004), (3) Loading/Appl ying Granulars via Push - Ty pe Spreader (ORETF data; MRID 449722 - 01; OMA003) , and (4) Loading/Appl ying Granulars via Belly Grinder (PHED) . Unit exposure values were taken from the Pesticide Handlers Exposure Database (PHED) and the Outdoor Residential Exposure Task Force (ORETF) studies. Residential risk assessments are based on estimates of what homeowners would typically treat, such as the size of a lawn. The factors used for the sulfentrazone assessment were from the Health Effects Di vision ScienceSulfentrazone Human - Health Risk Assessment DP# 364882

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### Advisory Committee Policy

12: Recommended Revisions to the Standard Operating Procedures for Residential Exposure Assessment which was completed on February 22, 2001. Noncancer risks were calculated using the Margin of Exposure (MOE) as des cribed in the occupational handler exposure section of this document. Short - term risks for residential handlers are presented in Table 5.1 . Intermediate - term exposures are not likel y because of the intermittent nature of applications by homeowners. Shor t - term combined dermal plus inhalation risks to residential handlers do not exceed HED’s level of concern for all scenarios . Even though a point of departure from an oral study was used to assess residential handler inhalation risks for sulfentrazone, giv en the large inhalation MOEs calculated for residential handlers (all >52,000), HED does not believe this assessment is under- protective of adult handlers. Table 5 .1. Residential Handler Exposure and Risks for Sulfentrazone . Exposure Scenario Crop or Target Application

Rate (lb ai/A) a Area

Treated Daily (acre) b Unit Exposures c

(mg/lb ai) Dose (mg/kg/day) MOE Combined MOE i Baseline Dermal d Baseline

Inhalation d Baseline

Dermal e Baseline

Inhalation f Baseline

Dermal g Baseline

Inhalationh Baseline

Dermal + Baseline Inhalation Mixer/Loader/Applicator Mixing/Loading/Applying Liquids with LowPressure Handwand (PHED) turf 0.375 0.5 100 0.03 0.31 0.000094 320 110,000 320 Mixing/Loading/Applying Liquids with Hose - End Sprayer (Residential ORETF data; MRID 449722 - 01; OMA004) turf 0.375 0.5 11 0.017 0.034 0.000053 2,900 190,000 2,900 Loading/Applying Granulars via Push - Type Spreader (ORETF data; MRID 449722 - 01; OMA003) turf 0.375 0.5 0.67 0.00088 0.0021 48,000 0.0000028 3,600,000 47,000 Loading/Applying Granulars via Belly Grinder turf 0.375 0.5 110 0.062 0.34 290 0.00019 52000 290 a . Application rates based on proposed uses on Gowan Company label GWN - 6010. b. Based on HED Science Advisory Committee Policy 12: Recommended Revisions to the Standard Operating Procedures for Residential Exposure Assessment (February 22, 2001), and on professional judgment . c. Dermal Dose (mg/kg/day) = daily unit exposure (mg/lb ai) x application rate (lb ai/acre or lb ai/gal) x acres or gal treated x 25% dermal absorption / body weight ( 6 0 kg). d. Inhalation Dose (mg/kg/day) daily unit exposure (μg/lb ai) x application rate (lb ai/acre or lb ai/gal) x acres or gal treated x 100% inhalation absorption / body weight ( 6 0 kg). e. Dermal MOE = NOAEL (40 mg/kg/day) / dermal daily dose (mg/kg/day). Level of concern = 100. f . Inhalation MOE = NOAEL (40 mg/kg/day) / inhalation daily dose (mg/kg/day). Level of concern = 100. g. Combined Baseline Dermal + I nhalation MOE = NOAEL (40 mg/kg/day) / Combine dermal + inhalation dose (mg/kg/day). 

### 5.2 Residential Post- application Exposure Sulfentrazone can be used in many areas that can be frequented by the general population including residential areas (e.g., home lawns). As a result, individuals can be exposed by entering these areas if they have been previousl y treated.Sulfentrazone Human - Health Risk Assessment DP# 364882

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### Based on the Agency's current practices, a quantitative postapplication inhalation exposure assessment was not performed for sulfentrazone at this time . However, volatilization of pesticides may

be a p otential source of postapplication inhalation exposure to individuals nearby to pesticide applications. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory

Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly /SAP/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report and may , as appropriate, developing policies and procedures, to identifying the need for and, subsequentl y, the way to incorporate postapplication inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative postapplication inhalation exposure assessment for prohexadione calcium . Short - term dermal and incidental oral exposures/risks have been assessed here and since the short - and intermediate - term PODs are the same, th e short - term assessment is protective of longer - term exposures. The populations that were considered in the assessment include:

 Residential Adults : these individuals are members of the general population that are exposed to chemicals by engaging in activities at their residences (e.g., in their lawns) and also in areas not limited to their residence (e.g., golf courses or parks) previously

treated with a pesticide. These kinds of exposures are attributable to a variety of activities and are usuall y addressed by HED in risk assessments by considering a representative activity as the basis for the exposure calculation.

 Residential Children : children are members of the general population that can also be exposed in their residences (e.g., on lawns and other residential turfgrass areas). These kinds of exposures are attributable to a variety of activities such as playing outside. Three to <6 year olds have been selected as the representative population for lawn turf assessments. 10 to 12 year olds have b een selected as the representative population for golf course turf. Postapplication exposure scenarios were developed for each residential setting where sulfentrazone can be used. The scenarios likely to result in postapplication exposures are as follows :  Dermal exposure from residue on lawns (adult, 10 - 12 year olds and 3 - <6 year olds );  Dermal exposure from residue on golf course turf (adult and 3 - <6 ye ar olds );  Hand - to - mouth transfer of residues on lawns ( 3 - <6 year olds );  Object - to - mouth tran sfer of residues on lawns ( 3 - <6 year olds );  In cidental ingestion of soil from pesticide - treated residential areas ( 3 - <6 year olds ) ; and  Episodic granular ingestion . HED combines risk values resulting from separate postapplication exposure scenarios when it is likely they can occur simultaneously based on the use pattern and the behavior associated withSulfentrazone Human - Health Risk Assessment DP# 364882

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### the exposed population and when the toxicological effects are similar. Since the toxicological effects are similar for dermal versus incidental oral P ODs, dermal risks were combined with incidental oral risks. Table 5.2 presents the postapplication MOE values calculated for adults, 10 - 12 year olds and 3

- <6 year olds after turf applications of sulfentrazone . Postapplication noncancer risks do not exceed HED’s level of concern for any of the scenarios assessed. Table 5 .2. Residential Risk Estimates for Postapplication Exposure .

Exposure Scenario Route of Exposure Dermal Transfer

Coefficient (μg/cm

2 ) Application

Rate (lb ai/acre) MOE at Day 0

(Lev el of Concern = 100) Com

bined MOE Adults Residential Turf (High Contact Activities) Dermal 14,500 0.375 980 N/A Residential Turf (Mowing) 3,400 4,200 Golfer 500 14,000 10 - 12 year olds Residential Turf (Mowing) Dermal 3,400 0.375 2,700 N/A Go lfer 500 9,300 3 - <6 year olds Residential Turf (High Contact Activities) Dermal 5,200 0.375 690 510 Hand to Mouth Activity on Turf Oral NA 2,500 Object to Mouth Activity on Turf 10,000 Incidental Soil Ingestion 750,000 Episodic Granul ar Ingestion 0.9% ai 1,400 N/A 

### 5.3 Spray Drift Spray drift is always a potential source of exposure to residents nearby to spraying operations. This is particularly

the case with aerial application, but, to a lesser extent, could also be a potential source of exposure from the ground application method additionally employed for sulfentrazone. The Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices. The Agency is now requiring interim mitigation measures for aerial applications that must be placed on product labels/labeling. The Agency has completed its evaluation of the new database submitted b y the Spray Dri ft Task Force, a membership of U.S. pesticide registrants, and is developing a policy on how to appropriatel y apply the data and the AgDRIFT ® 

### computer model to its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic method s. After the policy is in place, the Agency

may impose further refinements in spray

drift management practices to reduce off - target drift and risks associated with aerial as well as other application types where appropriate. 6.0 Aggregate Risk Assessment s and Risk Characterization Acute and chronic aggregate risks are made up only of dietary

sources; therefore, the exposure estimates provided in the dietary exposure anal ys is represent acute and chronic aggregate exposure, respectivel y. An aggregate canc er risk assessment was not performed becauseSulfentrazone Human - Health Risk Assessment DP# 364882

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### sulfentrazone is not considered to be a carcinogen. Short - and intermediate - term aggregate risks are made up of dietary

and non - dietary

sources of exposure. Since sulfentrazone is proposed for use on turf, han dler and post - application residential exposure is expected. Itis expected that the residential use will only

result in short - term exposures; however, since the short - and intermediate - term points of departure are the same, the short - term aggregate is pro tective of intermediate - term exposures. Short - and intermediate - term aggregate risk is made up of average dietary exposures from food and drinking water sources plus dermal and oral (children onl y) residential exposures. Dietary (food and drinking water) exposure is based on a Tier 1 chronic dietary exposure assessment. 6.1. Short- and Intermediate - Term Aggregate Risk Short - term exposures exist for adults and children from the registered turf application use ; however, since the short - and intermediate - term points of departure are the same, the short - term aggregate is protective of intermediate - term exposures . For short - and intermediate - term exposures, incidental oral and dermal exposure risk assessments are appropriate to aggregate due to similaritie s in the toxicity endpoints observed between the oral and dermal routes. The short and intermediate - term incidental oral and dermal exposures are combined with chronic dietary (food and water) exposure for determination of aggregate short - and intermediate - term exposures. HED uses chronic dietary exposure when conducting short - and intermediate - term aggregate assessments as they have determined that these will more accurately reflect exposure from food over the HED defined short - and intermediate - term interval than will acute exposure. For adults, there is no significant incidental oral exposure; therefore, onl y dermal exposure was appropriate to aggregate with dietary (food) and water. For young children, due primaril y to their hand - to - mouth activities , oral (non - dietary) and dermal exposures were aggregated with dietary (food) and water. Children can be expos ed through the following four post - application scenarios: 1) incidental ingestion (hand - to - mouth ) from contacting treated turf; 2) incidental ingestion (object - to - mouth) from contacting treated turf; 3) soil ingestion; and 4 ) dermal exposure from contact with treated turf. For the short - term aggregate, all three incidental oral exposures were aggregated with dermal and dietary exposures; however, it should be noted that this is an overly

conservative assessment because of the conservative nature of each individual assessment. For the intermediate - term aggregate, only the soil ingestion incidental oral pathway was aggregated with dermal and dietary since this is the only pathway that is assumed to potentially

result in intermediate - term exposures. Table 6 .1 summari zes the short - and intermediate - term aggregate exposures and risk estimates for 1 - 2 ye ar olds and adults . Since the aggregate MOEs are ≥ 10 0, short - and intermediate - term aggregate exposures to sulfentrazone are not of concern to HED.Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 43 of 58 Table 6.1 . Short - and Intermediate - t erm Aggregate Risk. Population Target

MOE Background Dietary + I ncidental Oral Exposures Residential Exposures Aggregate MOE (food, water, and residential) e Chronic Food and Water Exposure (mg/kg/day) Incidental Oral

Exposure (mg/kg/day) a Oral

MOE b Dermal

Exposure (mg/kg/day) Dermal

MOE c Inhalation

Exposure (mg/kg/day) Inhalation

MOE d General U.S. Population 10 0 0.001715 N/A 8, 0 00 0.3 10 320 0.000094 110,000 310 Children 1 - 2 years old 0.003 565 Short - term: 0.00 70 1,300 0.146 690 NA NA Short - term: 450 Intermediate term: 0.000019 3,900 Intermediate - term: 590 a. Short - term In cidental Oral Exposure = Hand -to - M outh exposure + Object -to - Mouth exposure +Soil I ngestion . In termediate term I ncidental Oral Exposure = Soil Ingestion. b. Oral MOE = NOAEL (14 mg/kg/day) ÷ ( chronic food/water exposure + incidental oral exposure) . c. Dermal MOE = NOAEL (100 mg/kg/day) ÷ (dermal exposure) . d. Inhalation MOE = NOAEL (10 mg/kg/day) ÷ ( inhalation exposure) . e. Aggregate MOE = 1/[(1/ oral MOE) + (1/dermal) + (1/inhalation) ] . 

### 7.0 Cumulative Risk Characterization/Assessment Unlike other pesticides for which EPA has followed a cumulative ris k approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to sulfentrazone and any other substance and sulfentrazone does not appear to produce a toxic metabolite produced b y other substances. For the purposes of this tolerance action, therefore, EPA has assumed that sulfentrazone does not have a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity an d to evaluate the cumulative effects of such chemicals, see the policy statements released by

EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechani sm on EPA’s website at http://www.epa.gov/pesticides/cumulative/. 8.0 Occupational Exposure/Risk Pathway The revised occupational exposure and risk assessment is summarized in the pending HED memorandum by K. Lowe ( D 364913 ). The proposed use is on head and stem Brassica , leafy green Brassica , melons, fruiting vegetables, okra, succulent peas, flax, strawberry , and tuberous and corm vegetables, and also impregnation to dry bulk fertilizer and applic ation with dry fertilizer. Occupational exposure is possible for individuals that handle the end - use products and/or for individuals that may enter treated areas. Therefore, occupational handler and postapplication exposure was assessed. 8.1 Occupation al Handler Exposure Sulfentrazone can be applied to the soil aerially , by chemigation, or using groundboom equipment. To impregnate sulfentrazone on dry bulk fertilizer, the product label recommendsSulfentrazone Human - Health Risk Assessment DP# 364882

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### that a closed rotary- drum mixer or other commonly used dry bulk fertilizer blender equipped with suitable spray

equipment be used. A slurry of the product is prepared and added to the impregnation spray

tank. Once impregnated on the dry- bulk fertilizer, it is applied by dry fertilizer spreader equipment. It is anticipated that the following scenarios could result in handler exposure:

• Mixing/loading liquids to support aerial applications, • Mixing/loading liquids to support chemigation applications, • Mixing/loading liquids to support groundboom applications, • Mixing/loading water - dispersible granules to support aerial applications, • Mixing/loading water - dispersible granules to support chemigation applications, • Mixing/loading water - dispersible granules to support groundboom applications, • Applying sprays with aircraft, • Applying sprays with groundboom equipment, • Flagging to support aerial spray applications, • Impregnating liquids onto dry bulk fertilizer in commercial settings, • Impregnating liquids onto dry bulk fertilizer on farm, • Impregnating water- dispersible granules onto dry bulk fertilizer in commercial settings, • Impregnating water- dispersible granules onto dry bulk fertilizer on farm, • Applying impregnated dry bulk fertilizer with commercial equipment, and • Applying impregnated dry bulk fertilizer with grower- owned equipment. No chemical - specific data were available with which to assess potential exposure to pesticide handlers. The estimates of exposure to pesticide handlers are based upon surrogate study data available in the PH ED ( August, 1998). There are no data to assess impregnating liquids or water- dispersible granules onto dry bulk fertilizer in commercial settings. The assumptions that the amount of sulfentrazone handled per day in commercial settings (500

– 960 tons) make it unlikely that open mixing/loading is used for this use . Therefore, as a reasonable surrogate for impregnation of dry

bulk fertilizer in commercial settings, unit exposure values from PHED for engineering controls (closed mixing/loading) are used. The onl y current engineering control for closed mixing/loading of water- dispersible granules is water- soluble packaging ; however, these data are only

used as a surrogate since no other data are available. The use of this data does not require that the sulf

entrazone product be re - formulated. For pesticide handlers, HED presents estimates of dermal exposure for “baseline” (i.e., workers wearing a single layer of work clothing consisting of a long - sleeved shirt, long pants, shoes plus socks and no protectiv e gloves), as well as for “baseline” and the use of protective gloves or other personal -protective equipment (PPE), as might be necessary . The sulfentrazone product labels direct applicators and other handlers to wear a long - sleeve shirt, long pants, chem ical resistant gloves and shoes plus socks. Handler exposure is expected to be short - or intermediate - term based on information provided on proposed labels. In addition, the short - and intermediate - term toxicological endpoints are the same; therefore, the estimates of risk for short - term duration exposures are protective of those for intermediate - term duration exposures. L ong - term exposures are not expected ; therefore, a long -Sulfentrazone Human - Health Risk Assessment DP# 364882

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### term assessment was not conducted. The average adult body weight of 60 kg wa s used for estimating dermal and inhalation dose, since the toxicological effects are female - specific. Tables 8.1.1 and 8.1.2 present the estimated risks for workers based on the short and intermediate - term dermal and inhalation exposures for foliar and dry bulk fertilizer applications, respectivel y . For both foliar applications and dry bulk fertilizer applications , none of the scenarios have risks of concern with the addition of chemical - resistant gloves (as recommended on the label).Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 46 of 58 Table 8.1.1. A gricultural Handler Exposure and Risk for Sulfentrazone . Crop or Target Application Rate (lb ai/A) a Acres

Treated Daily (acres) b Unit Exposures c Dose (mg/kg/day) MOEs Combined MOEs k

Dermal (mg/lb ai) Inhalation (ug/lb ai) Dermal g Inhalation h Dermal i Inhalation j Baseline Dermal + Baseline Inhalation PPE - G

Dermal + Baseline Inhalation Baseline d PPE - G e Baseline d Baseline PPE - G Baseline Baseline PPE - G Baseline

Mixing/Loading Liquid Concentrates for Aerial Applications flax 0.375 1200 2.9 0.023 1.2 22 0.17 0.009 5 580 1,100 5 380 Brassica , head and stem; Brassica, leafy green; and strawberry 0.375 350 2.9 0.023 1.2 6.3 0.05 0.0026 16 2,000 3,800 16 1,300 vegetables, tuberous and corm; and melons 0.25 350 2.9 0.023 1.2 4.2 0.034 0.0018 24 3,000 5,700 24 2,000 Mixing/Loading Liquid Concentrates for Chemigation Applications Brassica , head and stem; Brassica , leafy green; strawberry and flax 0.375 350 2.9 0.023 1.2 6.3 0.05 0.0026 16 2,000 3,800 16 1,300 vegetables, tuberous and corm; and melons 0.25 350 2.9 0.023 1.2 4.2 0.034 0.0018 24 3,000 5,700 24 2,000 succulent peas 0.188 350 2.9 0.023 1.2 3.2 0.025 0.0013 31 4,000 7,600 31 2,600 Mixing/Loading Liquids Concentrates for Groundboom Applications flax 0.375 200 2.9 0.023 1.2 3.6 0.029 0.0015 28 3,500 6,700 27 2,300 Brassica , head and stem; Brassica , leafy green; fruiting vegetables; okra; and strawberry 0.375 80 2.9 0.023 1.2 1.5 0.012 0.0006 69 8,700 17,000 69 5,700 vegetables, tuberous and corm; and melons 0.25 80 2.9 0.023 1.2 0.9 7 0.0077 0.0004 100 13,000 25,000 100 8,600 succulent peas 0.188 80 2.9 0.023 1.2 0.73 0.0058 0.0003 140 17,000 33,000 140 11,000 Mixing/Loading Dry Flowables for Aerial Applications flax 0.375 1200 0.066 0.066 0.77 0.5 0.5 0.0058 200 200 1,700 180 180 Brassica , head and stem; Brassica , leafy green; strawberry 0.375 350 0.066 0.066 0.77 0.14 0.14 0.0017 690 690 5,900 620 620 vegetables, tuberous and corm; and melons 0.25 350 0.066 0.066 0.77 0.096 0.096 0.0011 1000 1,000 8,900 930 930 Mixing/Loading Dry Flowables for Chemigation ApplicationsSulfentrazone Human - Health Risk Assessment DP# 364882

Page 47 of 58 Table 8.1.1. A gricultural Handler Exposure and Risk for Sulfentrazone . Crop or Target Application Rate (lb ai/A) a Acres

Treated Daily (acres) b Unit Exposures c Dose (mg/kg/day) MOEs Combined MOEs k

Dermal (mg/lb ai) Inhalation (ug/lb ai) Dermal g Inhalation h Dermal i Inhalation j Baseline Dermal + Baseline Inhalation PPE - G

Dermal + Baseline Inhalation Baseline d PPE - G e Baseline d Baseline PPE - G Baseline Baseline PPE - G Baseline Brassica , head and stem; Brassica , leafy green; strawberry; and flax 0.375 350 0.066 0.066 0.77 0.14 0.14 0.0017 690 690 5,900 620 620 vegetables, tuberous and corm; and melons 0.25 350 0.066 0.066 0.77 0.096 0.0 96 0.0011 1000 1,000 8,900 930 930 succulent peas 0.188 350 0.066 0.066 0.77 0.072 0.072 0.00084 1400 1,400 12,000 1,200 1,200 Mixing/Loading Dry Flowables for Groundboom Applications flax 0.375 200 0.066 0.066 0.77 0.083 0.083 0.00096 1200 1,200 10,000 1,100 1,100 Brassica , head and stem; Brassica , leafy green; fruiting vegetables; okra; strawberry 0.375 80 0.066 0.066 0.77 0.033 0.033 0.00039 3000 3,000 26,000 2,700 2,700 vegetables, tuberous and corm; and melons 0.25 80 0.066 0.066 0.77 0.022 0.022 0.00026 4500 4,500 39,000 4,100 4,100 succulent peas 0.188 80 0.066 0.066 0.77 0.017 0.017 0.00019 6000 6,000 52,000 5,400 5,400 Applying Sprays via Aerial Equipment flax 0.375 1200 Eng cont f: 0.005 No Data Eng cont: 0.068 Eng cont:

0.038 No Data Eng cont: 0.00051 Eng cont:

2,700 No Data Eng cont: 20,000 Eng cont:

2,300 No Data Brassica, head and stem; Brassica , leafy green; strawberry 0.375 350 Eng cont: 0.005 No Data Eng cont: 0.068 Eng cont:

0.011 No Data Eng cont: 0.00015 Eng cont:

9,100 No Data Eng cont: 67,000 Eng cont:

8,000 No Data vegetables, tuberous and corm; and melons 0.25 350 Eng cont: 0.005 No Data Eng cont: 0.068 Eng cont:

0.0073 No Data Eng cont: 0.000099 Eng cont:

14,000 No Data Eng cont: 100,000 Eng cont:

12,000 No Data Applying Spra

ys via Groundboom Equipment flax 0.375 200 0.014 0.014 0.74 0.018 0.018 0.00093 5700 5,700 11,000 3,700 3,700 Brassica , head and stem; Brassica , leafy green; fruiting vegetables; okra; strawberry 0.375 80 0.014 0.014 0.74 0.007 0.007 0.00037 14000 14,000 27,000 9,300 9,300 vegetables, tuberous and corm; and melons 0.25 80 0.014 0.014 0.74 0.0047 0.0047 0.00025 21000 21,000 41,000 14,000 14,000 succulent peas 0.188 80 0.014 0.014 0.74 0.0035 0.0035 0.00019 28000 28,000 54,000 19,000 19,000Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 48 of 58 Table 8.1.1. A gricultural Handler Exposure and Risk for Sulfentrazone . Crop or Target Application Rate (lb ai/A) a Acres

Treated Daily (acres) b Unit Exposures c Dose (mg/kg/day) MOEs Combined MOEs k

Dermal (mg/lb ai) Inhalation (ug/lb ai) Dermal g Inhalation h Dermal i Inhalation j Baseline Dermal + Baseline Inhalation PPE - G

Dermal + Baseline Inhalation Baseline d PPE - G e Baseline d Baseline PPE - G Baseline Baseline PPE - G Baseline Flagging for Aerial Sprays Applications Brassica , head and stem; Brassica , leafy green; strawberry; and flax 0.375 350 0.011 Not applicable 0.35 0.024 Not applicable 0.00077 4200 Not applicable 13,000 3,200 Not applicable vegetables, tuberous and corm; and melons 0.2 5 350 0.011 Not applicable 0.35 0.016 Not applicable 0.00051 6200 Not applicable 20,000 4,700 Not applicable a. Appl ication Rates based on proposed uses on registered labels for sulfentrazone product s EPA 379 - 3189 and 379 - 3220 and Revised Section B for th ese labels. b. Science Advisory Council Policy # 9.1 c. Unit Exposures based on PHED Version 1.1 . Engineering control unit exposure for applying sprays via aerial equipment = closed cockpit. d . Baseline Dermal: Long - sleeve d shirt, long pants, and no gloves; Baseline Inhalation: no respirator. e . PPE - G Dermal : Baseline plus chemical - resistant gloves. f. Eng Cont: closed mixing/loading system . g . Dermal Dose (mg/kg/day) = daily unit exposure (mg/lb ai) x application rate (lb ai/acre) x acres treated / body weight (60 kg adult female). h . Inhalation Dose (mg/kg/day) daily unit exposure (μg/lb ai) x application rate (lb ai/acre) x acres treated * inhalation absorption (100%) / body weight (60 kg adult female). i . Dermal MOE = NOAEL (1 00 mg/kg/day) / dermal daily dose (mg/kg/day). Level of concern = 100. j. Inhalation MOE = NOAEL (1 0 mg/kg/day) / inhalation daily dose (mg/kg/day). Level of concern = 100. k. Combined MOEs = 1 / ((1/ Dermal MOE) + (1/I nhalation MOE)). Table 8.1.2. Agricult ural Handler Exposure and Risk for Sulfentrazone – Dry Bulk Fertilizer Preparation . Exposure Scenario Application Rate a Ar ea

Treated Daily b Unit Exposures c Dose (mg/kg/day) MOE Combined MOEs k

Dermal Inhalation Dermal g Inhalation h Dermal i Inhalation j B aseline Dermal + Baseline Inhalation PPE - G Dermal

+ Baseline Inhalation Baseline e (mg/lb ai) PPE - G f

(mg/lb ai) Baseline e

(ug/lb ai) Baseline PPE - G Baseline Baseline PPE - G Baseline Mixer/Loader Mixing/Loading Liquids for Commercial I

mpregnation of Dry Bulk Fertilizers (PHED) 3.75 lb ai/ton 960 tons Eng cont d : 0.0086 No Data Eng cont: 0.083 Eng cont:

0.52 No

Data Eng cont:

0.005 Eng

cont: 190 No

Data Eng cont:

2,000 Eng cont: 180 No Data Mixing/Loading Liquids for Commercial I

mpregnation of D ry Bulk Fertilizers (PHED) 3.75 lb ai/ton 500 tons Eng cont: 0.0086 No Data Eng cont: 0.083 Eng cont:

0.27 No

Data Eng cont:

0.0026 Eng

cont: 370 No

Data Eng cont:

3,900 Eng cont: 340 No Data Mixing/Loading Liquids for On farm I mpregnation of Dry Bulk Fer tilizers (PHED) 0.375 lb ai/acre 160 acres 2.9 0.023 1.2 2.9 0.023 0.0012 34 4,300 8,300 34 2,900 Mixing/Loading Liquids for On farm I mpregnation of Dry Bulk Fertilizers (PHED) 0.375 lb ai/acre 80 acres 2.9 0.023 1.2 1.5 0.012 0.0006 69 8,700 17,000 69 5, 700Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 49 of 58 Table 8.1.2. Agricult ural Handler Exposure and Risk for Sulfentrazone – Dry Bulk Fertilizer Preparation . Exposure Scenario Application Rate a Ar ea

Treated Daily b Unit Exposures c Dose (mg/kg/day) MOE Combined MOEs k

Dermal Inhalation Dermal g Inhalation h Dermal i Inhalation j B aseline Dermal + Baseline Inhalation PPE - G Dermal

+ Baseline Inhalation Baseline e (mg/lb ai) PPE - G f

(mg/lb ai) Baseline e

(ug/lb ai) Baseline PPE - G Baseline Baseline PPE - G Baseline Mixing/Loading Dry Flowables for Commercial I

mpregnation of Dry Bulk Fertilizers (PHED) 3.75 lb ai/ton 960 tons Eng cont: 0.0098 No Data Eng cont: 0.24 Eng cont:

0.59 No

Data Eng cont:

0.014 Eng

cont: 170 No

Data Eng cont:

690 Eng cont: 140 No Data M ixing/Loading Dry Flowables for Commercial I

mpregnation of Dry Bulk Fertilizers (PHED) 3.75 lb ai/ton 500 tons Eng cont: 0.0098 No Data Eng cont: 0.24 Eng cont:

0.31 No

Data Eng cont:

0.0075 Eng

cont: 330 No

Data Eng cont:

1,300 Eng cont: 260 No Data Mixing/Loading Dry Flowables for On - farm I mpregnation of Dry Bulk Fertilizers (PHED) 0.375 lb ai/acre 160 acres 0.066 0.066 0.77 0.066 0.066 0.00077 1500 1,500 13,000 1,400 1,400 Mixing/Loading Dry Flowables for On - farm I mpregnation of Dry Bulk Fertilizers (P HED) 0.375 lb ai/acre 80 acres 0.066 0.066 0.77 0.033 0.033 0.00039 3000 3,000 26,000 2,700 2,700 Applicator Commercial Application of Dry Bulk Fertilizers using PHED tractor- drawn granular spreader

data) 0.375 lb ai/acre 320 acres 0.0099 0.0072 1.2 0.02 0.014 0.0024 5100 6,900 4,200 2,300 2,600 Commercial Application of Dry Bulk Fertilizers using PHED tractor- drawn granular spreader

data) 0.375 lb ai/acre 160 acres 0.0099 0.0072 1.2 0.0099 0.0072 0.0012 10000 14,000 8,300 4,600 5,200 On - farm Applications of Dry Bulk Fertilizers (using PHED tractordrawn granular spreader data) 0.375 lb ai/acre 160 acres 0.0099 0.0072 1.2 0.0099 0.0072 0.0012 10000 14,000 8,300 4,600 5,200 On - farm Applications of Dry Bulk Fertilizers (using PHED tractordrawn granular spreader data) 0.375 lb ai/acre 80 acres 0.0099 0.0072 1.2 0.005 0.0036 0.0006 20000 28,000 17,000 9,100 10,000 a. Appl ication Rates based on proposed uses on registered labels for sulfentrazone product s EPA 379 - 3189 and 379 - 3220. b. Industry input and professional judgment . c. Unit Exposures based on PHED Version 1.1 . d. Eng Cont: closed mixing/loading system . e. Baseline Dermal: Long - sleeve d shirt, long pants, and no gloves; Baseline Inhalation: no respirator. f. PPE - G Dermal : Baseline plus chemical - resistant gloves. g. Dermal Dose (mg/kg/day) = daily unit exposure (mg/lb ai) x application rate (lb ai/acre or lb ai/ton) x acres that will be treated or tons fertilizer treated / body weight (60 kg adult female). h. Inhalation Dose (mg/kg/day) daily unit exposure (μg/ lb ai) x application rate (lb ai/acre) x acres treated * inhalation absorption (100%) / body weight (60 kg adult female). i. Dermal MOE = NOAEL (1 00 mg/kg/day) / dermal daily dose (mg/kg/day). Level of concern = 100 0 . j. Inhalation MOE = NOAEL (1 4 mg/kg/day) / inhalation daily dose (mg/kg/day). Level of concern = 100 0 . k. Combined MOEs = 1 / ((1/ Dermal MOE) + (1/I nhalation MOE)).Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 50 of 58 

### 8.2 Occupational Post- application Exposure Based on the Agency's current practices, a quantitative o ccupational postapplication inhalation exposure assessment was not performed for sulfentrazone at this time. However, there are multiple potential sources of postapplication inhalation exposure to individuals performing postapplication activities in previ ously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Agency

sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly /SAP/meetings/2009/120109meeting.html ). The Agency is in the pro cess of evaluating the SAP report as well as available postapplication inhalation exposure data generated b y the Agricultural Reentry Task Force and may , as appropriate, develop policies and procedures, to identify the need for and, subsequently , the way t o incorporate occupational postapplication inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational postapplication inhalation exposure assess ment for sulfentrazone . Most of the proposed uses for sulfentrazone are soil - directed preplant or preemergent uses where no crop foliage is present. Currently , HED has no transfer coefficients or other data to assess post - application dermal exposures to soil by occupational workers. In general, such exposures are considered to be negligible. Therefore, for the proposed soil - directed uses, post - application exposures and risks to occupational workers were not assessed. One proposed use is for a postemergent application between the rows of fruiting vegetables and okra using ground equipment with shields or hoods to protect the crop foliage from exposure. Even though HED is not supporting the postemergent use based on the unavailability of metabolism data , post application worker exposure and risk were assessed for this proposed use. This assessment is considered to be a Tier I, screening - level estimate, demonstrating that there are minimal potential risks to workers re - entering fields treated with postem ergent applications of sulfentrazone. Since no post - application data were submitted in support of this registration action, dermal exposures during post - application activities were estimated using dermal transfer coefficients from the Expo SAC Policy Numbe r 3.1: Agricultural Transfer Coefficients, August 2000, summarized in Table 8.2 .1 below and the following assumptions:

• Application Rate = 0.375 lb ai/A for fruiting vegetable and okra applications • Exposure Duration = 8 hours per day • Body Weight = 60 kg for adult female • Dermal Absorption = 100%  

### Dislodgeable Foliar Residues: No sulfentrazone - specific dislodgeable foliar residue (DFR) data were available for agricultural crops . Therefore, this assessment uses HED’s default assumption that 20 percent of the application rate is available on day 0 (i.e., 12 hours after application) and the residue dissipates at a rate of 10 percent per day .Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 51 of 58 Table 8.2 . 1 . Anticipated Post- application Activities and Derm al Transfer Coefficients . Proposed Crops Pol icy Crop Group Category Transfer

Coefficients (cm 2/hr) Activities Eggplant, Groundcherry, Pepino, Pepper (includes bell pepper, chili pepper, pimento, sweet pepper), Tomatillo, Tomato and Okra Vegetables, Fruiting 700 Scouting, Thinning, Irrigation 

### The post - application exposure associated with the proposed new use is summarized in Table 8.2.2 . The resulting MOE is greater than 100 on day 0 (12 hours after application) and, therefore, does not exceed HED’s LOC. Table 8.2 .2 . Post - application Exposure an d Risk for Sulfentrazone . Crop Grouping/Crop Day s after Treatment DFR 1 (μg/cm2 ) Daily Dermal Dose 2 (mg/kg/day) MOE 3 Fruiting Vegetables and Okra 0

(12 hours) 0.84 0.079 1,300 1. DFR = Dislodgeable Foliar Residue = application rate (lb ai/A) x (1 - daily dissipation rate) t x 4.54E8 μg/lb x 2.47E - 8 A/cm2 x 20% DFR after initial treatment. 2 . Daily Dermal Dose = [DFR (μg/cm 2 ) x TC (700 cm2/hr) x 0.001 mg/μg x 8 hrs/day] / body weight (60 - kg adult female) . 3 . MOE = NOAEL/Daily Dose (Adult Dermal NOAEL = 100 mg/kg/day) . 

### REI : Since post - application risks were not a concern on day 0 (12 hours following application), the REIis based on the acute toxicity of sulfentrazone technical material which is classified as Category III for acute dermal toxicity and for eye irritation potential and Category IV for skin irritation potential. Sulfentrazone is not a dermal sensitizer. Under the Worker Protection Standard for Agricultural Pesticides, active ingredients classified as acute toxicity categories III or IV for these routes are assigned a 12 - hour REI. Therefore, the 12 - hour REIthat appears on the proposed label is adequate. 9.0 Data Needs and Label Recommendations 9.1 Toxicology

 Immunotoxicity

study (40 CFR revised Part 158 data requirement) . 9.2 Residue Chemistry

 Revised Section B (for conditional registration).  Revised Section F (for conditional registration).  As the reference standard for the metabolite HMS has expired 4/1/2008, the petitioner should submit a new standard (for conditional registration). If ne wSulfentrazone Human - Health Risk Assessment DP# 364882

Page 52 of 58 

### standards are being submitted, they should be sent to the ACL , which is located at Fort Meade, to the attention of Theresa Cole at the following address: USEPA National Pesticide Standards Repository /Anal ytical Chemistry Branch/OPP 701 Mapes Road F ort George G. Meade, MD 20755 - 5350 Please note that the extended zip code is required for delivery . 9.3 Occupational and Residential Exposure

 NoneSulfentrazone Human - Health Risk Assessment DP# 364882

Page 53 of 58 

### Attachment 1: Sulfentrazone Toxicity Profile Tables. Acute Toxicity Profile – Sulfentrazone. Guideline N o. Study T ype MRID(s) Results Toxicity Category 870.1100 Ac ute oral [rat] 41911605 LD 50 = 2855 (M & F) mg/kg III 870.1200 Ac ute dermal [mice] 41911606 LD50 = 711 (M & F) mg/kg III 870.1200 Ac ute dermal 42286400 LD50 > 2000 mg/kg/day III 870.1300 Ac ute inhalation [rat] 42471002 4 - hour, whole body exposure; LC50 > 4.13 mg/L III 870.2400 Ac ute eye irritation

[rabbit] 41911608 Corneal opacity, iritis, diffuse irritation within 24, clearing by day 4 III 870.2500 Ac ute dermal irritation

[rabbit] 41911609 No n - irritating IV 870.2600 Skin sensitization

[Guinea Pig] 41911610 Not a Dermal Sensitizer N/A Toxicity Profile for Sulfentrazone Guideline No./ Study T ype MRID No.

(year)/Classification/ Doses Results 870.3100 90 - Day oral toxicity (rat) 43004601 (199 0)

Acceptable/Guideline 0, 300, 1000, 3000, & 7000 ppm , M: 0, 3.3, 6.7, 19.9, 65.8, 199.3 & 534.9 mg/kg/day F: 0, 4, 7.7, 23.1, 78.1, 230.5 & 404.3 mg/kg/day Sy stemic Toxicity NOAEL = 19.9 mg/kg/day in males and 23.1 mg/kg/day in females Sy stemic Toxicity LOAEL= 65.8 mg/kg/day in males and 78.1 mg/kg/day in females, based on clinical signs of anemia (reduced hematocrit, hemoglobin, mean cell volume, and mean cell hemoglobin values during treatment). 870.3100 90 - Day oral toxicity (mice) 43616517 (1993) Acceptable/Guideline 0, 50, 100, 300, 550, 1000 & 3000 ppm M: 0, 10.3, 17.8, 60, 108.4, & 194.4 mg/kg/day F: 0, 13.9, 29, 79.8, 143.6, & 257 mg/kg/day Sy stemic Toxicity NOAEL = 60 mg/kg/day in males and 79.8 mg/kg/day in females Sy stemic Toxicity LOAEL= 108.4 mg/kg/day in males and 143.6 mg/kg/day in females, based on decreased body weights, body - weight gains, red blood cells, hemoglobin, hematocrit, and severity of splenic micropathology (increased incidence and severity of extramedullary hematopoiesis). 4 - wee k recovery period reversed all the treatment related effects except extramedullary hematopoiesis; however severity was reduced.Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 54 of 58 Toxicity Profile for Sulfentrazone Guideline No./ Study T ype MRID No.

(year)/Classification/ Doses Results 870.3150 90 - Day oral toxicity (dog) 42932102 (1992)

Acceptable/Guideline 0, 300, 800 & 2000 ppm M/F: 0/0, 10/10, 28/28 & 57/73 mg/kg/day Sy stemic Toxicity NOAEL= 28 mg/kg/day for males and females Sy stemic Toxicity LOAEL= 57/73 mg/kg/day (M/F), based on decreased body weights (7 - 10%) and bodyweight gains during first 5 weeks of study; decreased hemoglobin, hematocrit, mean cell v olume, mean cell hemoglobin and mean cell hemoglobin concentration, and increased absolute liver weights and alkaline phosphatase levels, and microscopic changes in the liver and spleen (pigmented sinusoidal microphages in the liver, swollen centrilobular hepatocytes and pigmented reticuloendothelial cells in the spleen). 870.3200 28 - Day dermal toxicity (rabbit) 44248301 (1996) Acceptable/Guideline 0, 10, 30, 100, 300 & 1000 mg/kg/day Sy stemic and Dermal Toxicity NOAEL = 1000 mg/kg/day ( Highest Dose Tested or HDT) Sy stemic and Dermal Toxicity LOAEL was not established. 870.3700a Prenatal Developmental (rat) 42932104 (1992) Acceptable/Guideline 0, 1, 10, 25 & 50 mg/kg/day Maternal NOAEL = 25 mg/kg/day Maternal LOAEL= 50 mg/kg/day, based upon increased relative splenic extramedullary hematopoiesis Developmental NOAEL = 10 mg/kg/day Developmental LOAEL = 25 mg/kg/day, based upon decreased mean fetal weights, and retardation in skeletal development evidenced by an increased number of litters with any variation and by decreased number of caudal vertebral and metacarpal ossification sites. 870.3700 Prenatal developmental (rat) 43651003 (1992) Acceptable/Non - Guideline 0, 25, & 50 mg/kg/day Study was conducted to evaluate external and cardiac abnormalities Maternal NOAEL = 25 mg/kg/day Maternal LOAEL =50 mg/kg/day, based on decreased mean body weights during gestation, and decreased litter size. Developmental NOAEL = 25 mg/kg/day Developmental LOAEL = 50 mg/kg/day, based on significant reductions in the number of im plantations and percentage of live fetuses, increase in the percentage of early resorptions, and decreased fetal body weights . Supplemental study to the 1992 Developmental Toxicity Study in Rats (MRID 42932104)Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 55 of 58 Toxicity Profile for Sulfentrazone Guideline No./ Study T ype MRID No.

(year)/Classification/ Doses Results 870.3700 Prenatal dermal developmental (rat) MRID 42932105 (1992) Acceptable/Guideline 0, 5, 25, 50, 100, & 250 mg/kg/day Maternal NOAEL > 250 mg/kg/day Maternal LOAEL was not established Developmental NOAEL = 100 mg/kg/day Developmental LOAEL= 250 mg/kg/day, based on decreased fetal body weight; i ncreased incidence of fetal variations: hypoplastic or wavy ribs, incompletely ossified lumbar vertebral arches, and incompletely ossified ischia or pubis; and reduced number of thoracic vertebral and rib ossification sites. 870.3700b Prenatal Developmental (rabbit) MRID 42932106 (1993) Acceptable/Guideline 0, 100, 250, & 375 mg/kg/day Maternal NOAEL = 100 mg/kg/day Maternal LOAEL = 250 mg/kg/day, based on increased abortions, clinical signs (hematuria and decreased feces), and reduced body - weight gain De velopmental NOAEL = 100 mg/kg/day Developmental LOAEL = 250 mg/kg/day, based on increased resorptions, decreased live fetuses per litter, and decreased fetal weights. 870.3800 2 - Generation reproduction and fertility effects (rat) 43345408 (1994) Acceptabl e/Guideline 0, 200, 500, & 700 ppm M/F: 0, 14/16, 33/40, & 46/56 mg/kg/day Parental Toxicity NOAEL =14 (M) and 16 (F) mg/kg/day Parental Toxicity LOAEL = 33 (M) and 40 (F) mg/kg/day based on decreased maternal body weight/body- weight gain during gestation in both generation (P & F1) and reduced premating body weight gain in second generation (F1) males. Reproductive Toxicity NOAEL = 14 (M) and 16 (F) mg/kg/day Reproductive Toxicity LOAEL =33 (M) and 40 (F) mg/kg/day, based on increased duration of gestation in females and degeneration and/or atrophy of the germinal epithelium of the testes and oligospermia and intratubular degenerated seminal material in the epididymis of F1 males. Offspring Toxicity NOAEL=14 (M) and 16 (F) mg/kg/day Offspring Toxicity LOAEL= 33 (M) and 40 (F) mg/kg/day, based on reduced prenatal viability (fetal & litter), reduced litter size, increased no. of stillborn pups, reduced pup and litter postnatal survival and decreased pup body weights throughout lactation.Sulfentrazone Human - Health Risk Assessment DP# 364882

Page 56 of 58 Toxicity Profile for Sulfentrazone Guideline No./ Study T ype MRID No.

(year)/Classification/ Doses Results 870.3800 1 - Generation reproduction and fertility effects (rat) 43869101(1995) Acceptable/Nonguideline 0, 50, 100, 200, & 500 ppm F0 M/F: 0, 3.9/4.1, 7.8/13.4, 16/16 & 40/43 mg/kg/day F1 M/F: 0/0, 4.5/5.0, 9.2/10.1, 18/20 & 45/51 mg/kg/day Sy stemic/Developmental Toxicity NOAEL =20 (F) mg/kg/day Sy stemic/Developmental Toxicity LOAEL = 51 (F) mg/kg/day, (F1 females), based on decrease in pre mating body - weight gain (10%) Offspring and Reproductive Toxicity NOAEL = 16 mg/kg/day (M/F) mg/kg/day Offspring and Reproductive Toxicity LO AE L F1 = 40 (M/F) mg/kg/day, based on reduced gestation day 20 fetal weights; decreased postnatal day 0, 4 and 7 pup weights; decreased pup survival; delayed vaginal patency; reduced epididymal, prostate, and testicular weights. Additional information sup ports the conclusions reached in the 2 - gen reproduction study (MRID 43345408) 870.4100b Chronic toxicity (dog) 43345406 (1994) Acceptable/Guideline 0, 300, 800, and 1800 ppm M/F: 0, 9.9/10.4, 24.9/29.6 & 61.2/61.9 mg/kg/day Sy stemic toxicity NOAEL = 24.9/29.6 mg/kg/day for males/and females Sy stemic toxicity LOAEL = 61.2/61.9 mg/kg/day (M/F), based upon compensated normochromic microcytosis. 870.4200 Carcinogenicity rodents (mouse) 43345407 (1994) Acceptable/Guideline 0, 300, 600, 1000, & 2000 ppm M/F: 0, 46.6/58.0, 93.9/116.9, 160.5/198.0 & 337.6/407.1 mg/kg/day Sy stemic toxicity NOAEL = 93.9 mg/kg/day for males and 116.9 mg/kg/day for females Sy stemic toxicity LOAEL = 160.5 mg/kg/day for males and 198.0 mg/kg/day for females, based on dose - related decrea ses in hemoglobin and hematocrit by study termination. No evidence of carcinogenicity. 870.4300 Com bined chronic toxicity/carcinogenicity rodents (rat) 43345409 (1994) Acceptable/Guideline M: 0, 600, 1000, 2000, & 3000 ppm F: 0, 300, 600, 1000 & 2000 ppm M/F: 0/0, 24.3/20, 40/36.4, 82.8/67, & 123.5/124.7 mg/kg/day Sy stemic toxicity NOAEL = 40 mg/kg/day for males and 36.4 mg/kg/day for females Sy stemic toxicity LOAEL = 82.8 mg/kg/day for males and 67 mg/kg/day for females, based on dose - related decreased bo dy weights (11 & 19%), body- weight gains (13 & 26%), food consumption (13 & 19%), hemoglobin, hematocrit, mean cell volume, and mean cell hemoglobin. Increased nucleated red blood cells and reticulocytes in bone of females at 124.7 mg/kg/day. No evidence of carcinogenicity.Sulfentrazone Human - Health Risk Assessment DP# 364882

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(year)/Classification/ Doses Results 870.5100 Gene Mutation: Ames assay Gene Mutation: HGPRT 41911611 (1986) Acceptable/Guideline Salmonella typhimurium strains TA 1535, TA1538, TA1537, TA 98 and TA100 were exposed to Sulfentrazone Technical (95.5%) at concentrations of 10 0 - 10,000 ug/plate with or without S9 activation (both trials). No evidence of compound - induced cytotoxicity wa s evident either in presence or in absence of S9 activation. The positive controls induced the expected mutagenic responses in the appropriate te ster strain. Sulfentrazone was considered not mutagenic under any test condition.

870.5300 In vitro mammalian cell gene mutation assay (mouse lymphoma) 43004604 (1992) Acceptable/Guideline Mouse lymphoma (L5178Y TK+/ - CHO) cells were exposed to Sulfentrazone Technical (94.2%) in non activated dose ranges of 424 - 1308ug/ml (Trial 1) and 1308 - 3000 ug/ml (Trial 2); With S9 activation dose ranges of 424 - 1407 ug/ml (Trial 1) and 915 - 1800 ug/ml (Trial 2). In a forward gene mutation assay, sulfentrazone at precip itating levels were equivocally positive in the absence of S9 activation. This response was not repeated at doses up to 1800:g/ml in the presence of S9 activation.

870.5395 Mammalian erythrocyte micronucleus test 43004605 (1992) Acceptable/Guideline Grou ps of 5 male and 5 female ICR mice received single intraperitoneal injection of 85, 170, and 340 mg/kg Sulfentrazone Technical (94.2%). Test material was administered in corn oil and bone marrow cells harvested at 24, 48, and 72 hours post - dosing. Cyclopho sphamide at 30 mg/kg was used as positive control. The test was negative in mice administered single intraperitoneal doses of 85 - 340 mg/kg. The 340 mg/kg dose was estimated to be approximately 80% of the LD50/7. No evidence of a cytotoxic effect on the target organ and no significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow cells.

870.5450 Dominant lethal assay - rodent 44248302 (1996) Acceptable/Guideline In dominant lethal assay male rats were dosed at 0, 100 , 225, or 450 mg/kg/day for 5 days, and mated to untreated females sequentially for 10 weeks to determine the level of fetal deaths due to dominant lethal mutations. There were no significant differences from negative controls in the proportion of early de ad: total im plants, and (total) dead: total implants. Based on the results, sulfentrazone is considered negative for inducing dominant lethal mutations in pre - meiotic, meiotic, and post - meiotic germ cells of male rats under conditions of this assay up to the estimated MTD.Sulfentrazone Human - Health Risk Assessment DP# 364882

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(year)/Classification/ Doses Results 870.6200 Acute Neurotoxicity Study 43345405 (1994) Acceptable/Guideline 0, 250, 750, & 2000 mg/kg Sy stemic Toxicity NOAEL = 250 mg/kg/day Sy stemic Toxicity LOAEL = 750 mg/kg/day, based upon increased incidence of clinical signs, FOB findings, and decreased motor activity which was reversed by day 14 post dose. No evidence of neuropathology at any dose. 870.6200 Subchronic Neurotoxicity Study 43345405 (1994) Acceptable/Guideline 0, 500, 2500, or 5000 ppm (0/0, 30/37, 150/180, or 265/292 mg/kg/day [M/F]) NOAEL = 500 ppm (30/37 mg/kg/day) LOAEL = 2500 ppm (150/180 mg/kg/day) based on increased incidence of clinical signs (M&F), decreased BW, BWG, and FC (F), and increased mo tor activity at week 13 only (F) No evidence of neuropathology at any dose. 870.7485 Metabolism and pharmacokinetics (rat) 43345410 (1994) Acceptable/Guideline Phenyl - 14C - sulfentrazone (98% pure.) was administered to Sprague Dawley rats (5 animals/sex/dose) by gavage as a single dose at levels of 50 and 500 mg/kg, or as a single dose of 50 mg/kg following a 14 - day pretreatment with non radioactive sulfentrazone (50 mg/kg/day). Sulfentrazone was readily absorbed and 84 to 104% of the administered dose was excreted in urine and feces within 72 hours. There were no major sex differences in the pattern of excretion. Almost all the radioactivity in the urine wa s 3 - hydroxy - methyl - F6285 (84 - 104% of the administered dose). In the feces, HMS accounted for 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 - F6285 (excreted in the urine). A small amount of 3 - hydroxymethyl - F6285 was also converted to 3 - carboxylic acid - F6285 (excreted in the urine and feces). Published literature D e Ca stro , et al . , (2007) Acceptable/non - guideline 0, 25, or 50 mg/kg bw/day D ose - dependent, statistically significant delayed ear opening, decreased grip response and rearing frequency, and increased surface righting reflex reaction time observed at ≥ 25 mg/kg/day ; no effect on maternal body weight (only parameter tested in dams ) during gestation . The results of this non - guideline study were published in the open literature. Due to limitations in study conduct and reporting of the statistical analysis, the study is of limited value in risk assessment.