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, Leafy Greens, Subgroup 5B; 

Melon Subgroup 9A; Fruiting Vegetable, Group 8 and Okra; Pea, Succulent; 

Flax; Strawberry; and Tuberous and Corm Vegetable, Subgroup 1C. HumanHealth Risk Assessment.

PC Code: 129081 DP Barcode: D364882

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

TXR No.: NA CAS No.: 122836-35-5

MRID No.: NA 40 CFR: §180.498

FROM: Kelly Lowe, Environmental Scientist

Robert Mitkus, PhD, DABT, Toxicologist

Chester Rodriguez, Ph.D., Pharmacologist

William D. Wassell, Chemist

Julie Van Alstine, MPH, Environmental Health Scientist

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)

NOTE: 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 

postapplication assessment.
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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-oxo-1H-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 by Lisa Austin (RAB1); the updated hazard assessment was 

provided by Robert Mitkus and Chester Rodriguez (RAB1); the residue chemistry review and 

dietary exposure assessments were provided by William Wassell (RAB1) and Julie Van Alstine

(RAB1); the occupational/residential exposure assessment and updated risk assessment were

provided by Kelly Lowe (RAB1); and the drinking water assessment was provided by Michael 

Barrett of the Environmental Fate and Effects Division (EFED).
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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 Structure 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........................................................... 52
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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 biosynthetic 

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 (source: 

http://courses.cropsci.ncsu.edu/cs414/CH_11.PDF).

The Interregional Research Project No. 4 (IR-4) has submitted a petition proposing the 

establishment 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-1H-1,2,4-triazol-1-

yl]phenyl]methanesulfonamide] and its metabolites HMS [N-(2,4-dichloro-5-(4-

(difluoromethyl)-4,5-dihydro-3-hydroxymethyl-5-oxo-1H-1,2,4-triazolyl)phenyl)methanesulfonamide)] and DMS [(N-2,4- dichloro-5-[4-(difluoromethyl)-4,5-dihydro5-oxo-1H-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 ppm

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

Martynia......................................................................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 soybean seed at 0.05 ppm. In addition, 
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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 Exemptions; 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. Finally, 

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 straw 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 Spartan®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 enzyme protoporphyrinogen oxidase (PPO) in target plants, and the 

results of mammalian toxicity studies were consistent with this mechanism of action, given that 

PPO is an important enzyme in the heme synthetic pathway in mammals. Specifically, 

disruption of heme synthesis 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 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 maternally toxic, although clear No 

Observed Adverse Effect Levels (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 maternally toxic dose (slightly decreased body weight gain).

Although sulfentrazone is considered a developmental toxicant, the developing nervous system is 

not considered a selective target. A published non-guideline developmental neurotoxicity study

in the rat by De Castro et al. (2007) with no established NOAEL failed to demonstrate 
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conclusively developmental neurotoxicity and yielded 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 relatively 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 systemic 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 required. 

Carcinogenicity studies in rats and mice showed no evidence of increased incidence of tumor 

formation due to treatment with sulfentrazone, and sulfentrazone is not considered to be 

genotoxic.

Exposure Assessment

Dietary Exposure and Risk

The acute and 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 analyses assumed DEEMTM (ver. 7.81) default processing factors, 100% 

crop-treated (CT), and tolerance-level residues for all commodities. The analyses also 

incorporated the drinking water estimates provided by EFED (0.0358 ppm and 0.026 ppm for the 

acute and chronic analysis, respectively). 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 95th

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 concern. 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 analysis represent acute and chronic aggregate 

exposure, respectively. 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 shortand intermediate-term points of departure are the same, the short-term aggregate is protective of 

intermediate-term exposures. Short- and intermediate-term aggregate risks 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.
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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 intermediateterm dermal 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 

HED’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 early 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). Postapplication 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 intentionally 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 

fundamentally unethical nor significantly deficient relative to standards of ethical research 
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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 with U.S. Executive Order 12898, Federal Actions 

to Address Environmental Justice in Minority Populations and Low-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 activities 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 Surveys of Food Intakes by Individuals (CSFII) and are used 

in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed 

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 year 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 consider exposure to bystanders 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 (proposed 

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 ppm
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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

Martynia......................................................................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

Toxicology

 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/Analytical 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

Notes to RD: 

(1) As the enforcement method for plant commodities determines free and conjugated forms of 

the analytes, 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. Tolerances should be proposed using this tolerance 

expression. As the proposed directions for use on fruiting vegetables include postemergence 

applications, HED concludes metabolism data are not available to support the 

postemergence applications.
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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 vegetable 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 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 biosynthetic pathway and leads to the subsequent buildup 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 Brassica, 

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 (PHIs) were proposed for these crops.

A list of the sulfentrazone end-use products relevant to this registration request is presented in 

Table 2.1.1. The proposed crop use directions are summarized in Table 2.1.2. Information 

regarding rotational crop restrictions is listed in Table 2.1.3.
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Table 2.1.1. Summary of Proposed End-Use Products.

Trade Name Reg. No. ai (% of 

formulation)

Formulation 

Type1

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: flax; 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 NS
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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 0.1875 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] 

0.094-0.375

[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.

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 dependent 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 aerial equipment. 
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Table 2.1.3. Plantback Intervals for Use of Sulfentrazone.

Rotational Crop1Plantback 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

Soybean Anytime

Sugar Beets 36

Sugarcane Anytime

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-month 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) As metabolism data are not available to support postemergence 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.
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2.2 Structure and Nomenclature

Table 2.2. Structure and Nomenclature of Sulfentrazone and Its Metabolites.

Chemical structure

Cl

Cl

HN

SO2CH3

N

N

N

O

CH3

CHF2

Common name Sulfentrazone

Company experimental name F6285; FMC 97285

IUPAC name 2',4'-dichloro-5'-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol1-yl)methanesulfonanilide

CAS name N-(2,4-dichloro-5-(4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-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

HN

SO2CH3

N

N

N

O

CHF2

Common name 3-desmethyl sulfentrazone; DMS

Chemical name N-(2,4-dichloro-5-(4-(difluoromethyl)-4,5-dihydro-5-oxo-1H-1,2,4-triazol-1-

yl)phenyl)methanesulfonamide

Chemical structure of HMS 

metabolite

Cl

Cl

HN

SO2CH3

N

N

N

O

CHF2

OH

Common name 3-hydroxymethyl sulfentrazone; HMS
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Table 2.2. Structure and Nomenclature of Sulfentrazone and Its Metabolites.

Chemical name N-(2,4-dichloro-5-(4-(difluoromethyl)-4,5-dihydro-3-hydroxymethyl-5-oxo-1H1,2,4-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 102 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 Characterization/Assessment

A detailed hazard characterization and dose response assessment for sulfentrazone were 

presented in previous HED risk assessments in 2003 and 2009 (D274568 and D362324). 

However, both the hazard characterization and toxicity profile tables have been updated since the 

2009 risk assessment 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 systemic toxicity was seen via the dermal route up to the limit dose (1,000

mg/kg/day) in a 28-day dermal toxicity study in non-pregnant rabbits. Sulfentrazone inhibits the 

enzyme PPO in target plants, and the results of mammalian toxicity studies were consistent with 

this mechanism of action, given that PPO is an important enzyme in the heme synthetic pathway

in mammals. Specifically, disruption of heme synthesis 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 studies in the rat, as well as at doses that were not maternally

toxic, although clear NOAELs were attained in both studies. In rabbits, developmental effects 

such as decreased pup viability were observed at a maternally toxic dose (clinical signs of 

toxicity, 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 increased number of stillborn pups. Pup 
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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 (slightly 

decreased body-weight gain, particularly 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 decreased motor activity were observed at ≥750 mg/kg/day; 

however, complete recovery was observed in 14 days 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 gain, 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 and 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 prenatally to sulfentrazone. Neurotoxicology 28(6):1249-59.), several dosedependent 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 physical and reflex 

development, known to be affected by 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, erroneously 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), unclearly 

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 NOAEL 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 effort 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.
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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 previously 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 weakly clastogenic in the in vitro mouse lymphoma assay in 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 readily absorbed from the GI tract of rats following oral dosing and nearly 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 bioaccumulation.

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 

weight 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, particularly 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 ossification 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 repeatedexposure 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 skeletal development as evidenced by an increased number of 

litters with any variation and a decreased number of caudal vertebral and metacarpal ossification 
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sites. This study provides developmental effects that are likely due to repeated exposures to 

sulfentrazone and its NOAEL is the lowest in the database. Furthermore, the developmental 

effects of fetal body weight deficits and delayed skeletal development at the LOAEL of 25 

mg/kg/day (NOAEL of 10 mg/kg/day) are consistent with those reported in the 2-generation 

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 years.

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 weights, delays 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 deficits 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, developmental 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 route 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 assessments, 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 risk assessment.
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Table 3.1. Summary 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 = 

14

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

1X

aRfD = aPAD = 

0.14 mg/kg/day

2-Gen Reproductive Toxicity Study - Rat

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.

Acute Dietary

(General population

including infants

and children)

NOAEL = 

250 

mg/kg/day

UFA = 10X

UFH = 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 Dietary

(all populations)

NOAEL= 

10

mg/kg/day 

UFA = 10X

UFH = 10X

FQPA SF = 

1X

cRfD = cPAD =

0.10 mg/kg/day

Prenatal Developmental Toxicity - Rat

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.

Short- (1-30 days) 

and IntermediateTerm (1-6 months) 

Incidental Oral 

Offspring

NOAEL= 

14 

mg/kg/day

UFA = 10X

UFH = 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 LongTerm (>6 months) 

Dermal

NOAEL=

100 

mg/kg/day

UFA = 10X

UFH = 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 incidences 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 LongTerm (>6 months) 

Inhalation

NOAEL= 

10

mg/kg/day

UFA = 10X

UFH = 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, 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.

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. UFA = 

extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human 

population (intraspecies). UFL = 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.
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3.2 Food Quality Protection Act (FQPA) Considerations

The RAB1 risk assessment team concluded that the FQPA Safety Factor (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 treatmentrelated 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 dysfunction (e.g., anemia). Unlike white blood 

cells (leukocytes) which are cells of the immune system, red blood cells function to 

deliver oxygen 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 

leukocyte counts (an indicator of immune function). Thus, the overall weight of evidence 

indicates that this chemical does not directly target the immune system. Sulfentrazone 

also does not belong to a class of chemicals (e.g., the organotins, heavy metals, or 

halogenated aromatic hydrocarbons) that would be 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, based on the above considerations, 

EPA does not believe that conducting a functional 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 increased 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. 

However, 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, thereby 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 system is a target for sulfentrazone. The FOB findings were very nonspecific 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 reflex 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-generation 
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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 study 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 reproduction 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 assessments were performed based on 100 PCT and tolerancelevel 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 employs 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 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems 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 call-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. Accordingly, EPA anticipates issuing future EDSP test orders/data call-ins for all 

pesticide active ingredients. 
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For further information on the status of the EDSP, the policies 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 by 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 soybeans and confined rotational crops were 

submitted in conjunction with the petition for use on soybeans (PP#4F04407). Sulfentrazone in 

plant commodities is metabolized via four different pathways: 

(1) Oxidation of the 3-methyl group to form HMS, followed by further oxidation to form 

sulfentrazone carboxylic acid which is decarboxylated to DMS. 

(2) Hydrolysis of the trifluoromethyl group to form desdifluoromethyl sulfentrazone which is 

oxidized and decarboxylated to form desdifluoromethyl desmethyl sulfentrazone. 

(3) Hydrolysis of the sulfonamide group to form desmethylsulfonyl sulfentrazone. 

(4) Scission of the phenyl and triazole rings to produce methyl triazole. 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 soybeans, and that sulfentrazone and the 

metabolites 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 types of crops (D220548, 3/13/96, G. 

Kramer). 
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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 analytes, 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 were submitted in conjunction with the 

soybean petition (PP#4F04407). The metabolism of sulfentrazone in livestock differs from that 

in plants as metabolism proceeds only by oxidation of the 3-methyl group to HMS, followed by

further oxidation to form sulfentrazone carboxylic acid, which is decarboxylated 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-carboxylic 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) and Spartan®75DF (75% ai) (see Memo, L. Lui, 9/15/09, D366552). For a complete 

summary of the drinking water assessments for sulfentrazone 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 Ground Water (SCI-GROW) model) and surface water [using the 

FQPA Index Reservoir Screening Tool (FIRST) model] for sulfentrazone and 3-carboxylic acid 

sulfentrazone (see Table 4.2 below). These values generally 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 

horseradish. 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 incorporation which would reduce surface 

water concentration values.
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Table 4.2. Tier 1 EDWCs of Sulfentrazone and 3-Carboxylic Acid Sulfentrazone in Drinking Water.

Chemical

Surface Water (ppb) Groundwater (ppb)

Acute Chronic Acute 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) analytical method for the determination of free and conjugated 

residues of sulfentrazone, DMS, and HMS in/on various matrices was submitted with a petition 

for a sulfentrazone tolerance on soybeans (PP# 4F04407). A petition method validation was 

successfully completed by the Agency’s Analytical Chemistry Laboratory (ACL). The limit of 

quantification (LOQ) and limit of detection (LOD) were determined to be 0.05 ppm and 0.005-

0.025 ppm, respectively. HED concluded that the method is suitable for enforcement purposes 

(D233520, G. Kramer, 3/25/97). The method was forwarded to the Food and Drug 

Administration (FDA) for inclusion in the Pesticides Analytical 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 analyzed for 

residues of sulfentrazone and its metabolites DMS and HMS using the FMC method entitled, 

“Analytical Methodology for the Determination of Sulfentrazone, 3-Desmethyl Sulfentrazone, 

and 3-Hydroxymethyl Sulfentrazone in/on Various Matrices, Study Number 162MVL96R1” 

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 cantaloupe, 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 datacollection 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 by 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 304 
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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 PHIs of 68-158 days. 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 days following one broadcast application either to soil 72 

hours prior to transplanting or to direct seeded broccoli at the 2- to 4-leaf 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 from Broccoli Field Trials with Sulfentrazone.

Commodity

Total Applic. 

Rate

(lb ai/A)

PHI 

(days)

Residue Levels(ppm)

n Min. Max. HAFT1 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.
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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 heads with and without 

wrapper leaves, respectively, harvested 68-104 days following a single ground broadcast 

application of the 75% DF formulation at 0.375 lb ai/A (1x rate) made 1-3 days prior to 

transplanting or at the 2- to 4-leaf growth stage (33 days 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 combined 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, 

subgroup 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 days 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, respectively. 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, respectively.
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Table 4.3.2. Summary of Residue Data from Mustard Green Field Trials with Sulfentrazone.

Commodity

PHI

(days)

Trt 

Plot

No.

Total

Applic.

Rate

(lb ai/A)

Residue Levels(ppm)

n Min. Max. HAFT1 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 0.092-0.108 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, subgroup 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 860.1500 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 on 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 Guidance 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 ppm 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 residues 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% DF 
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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 from Succulent 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

Pea, 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, the 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 ediblepodded) 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 days 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 0.75 lb ai/A (2.0x); see Table 4.3.4. Total combined residues of 
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sulfentrazone, DMS, and HMS were all <0.15 ppm in/on all treated samples of peppers and 

tomatoes. 

Table 4.3.4. Summary of Residue Data from Fruiting Vegetable Field Trials with Sulfentrazone.

Commodity

PHI

(days)

Trt 

Plot

No.

Total

Applic.

Rate

(lb ai/A)

Residue Levels(ppm)

n Min. Max. HAFT1 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 --

Tomato 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 <0.05 <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 --

Tomato 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 --

Tomato 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 --

Total
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Table 4.3.4. Summary of Residue Data from Fruiting Vegetable Field Trials with Sulfentrazone.

Commodity

PHI

(days)

Trt 

Plot

No.

Total

Applic.

Rate

(lb ai/A)

Residue Levels(ppm)

n Min. Max. HAFT1 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 --

Tomato 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-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 peppers (bell and non-bell) and tomatoes are 

adequate. 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 vegetables, 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 of 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 (peppers 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.
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Melon subgroup 9A: (47311403.der.doc)

The results of the field trials indicate that residues of sulfentrazone, DMS, and HMS were below 

the LOQ (<0.05 ppm) in/on all samples of cantaloupe harvested 59-94 days 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, 

respectively. The results of these field trials are summarized in Table 4.3.5. 

Table 4.3.5. Summary of Residue Data from Cantaloupe Field Trials with Sulfentrazone.

Commodity

PHI

(days) Trt

No.

Total

Applic.

Rate

(lb ai/A)

Residue Levels (ppm)

n Min. Max. HAFT1 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 <0.05 <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

Cantaloupe, 

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.

Conclusions: 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 revised Section F is required since the petitioner has proposed 

a crop subgroup tolerance level of 0.10 ppm.
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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 days 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 (Treatment 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 from Strawberry Field Trials with Sulfentrazone.

Commodity

Total Applic. 

Rate

(lb ai/A)

PHI

(days)

Residue Levels (ppm)

n Min. Max. HAFT1 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 0.05 <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 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 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 days after a single 

preemergence broadcast soil application of a 75% DF formulation or mixture of two 75% DF 

formulations of sulfentrazone at a rate of ~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.
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Table 4.3.7. Summary of Residue Data from Flax Field Trials with Sulfentrazone.

Commodity Total Applic. 

Rate (lb ai/A)

PHI 

(days)

Residue Levels (ppm)

n Min. Max. HAFT1 Median Mean Std. Dev.

Proposed Use Pattern: Preemergence application at a maximum seasonal rate of 0.375 lb ai/A

Sulfentrazone

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 0.365-0.383 111-123 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 residue 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

Brassica, 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.
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Table 4.3.8. Tolerance Summary for Sulfentrazone.

Commodity

Proposed Tolerance 

(ppm)

Recommended 

Tolerance (ppm) Comments

Strawberry 0.05 0.15 The established time-limited 

tolerance for strawberry under 

180.498(b) should be removed 

concomitantly when the permanent 

strawberry tolerance is established.

Vegetable, 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 established.

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 

soybean petition (PP#4F04407). The metabolism of sulfentrazone in livestock differs from that 

in plants as metabolism proceeds only by oxidation of the 3-methyl group to form HMS, 

followed by further oxidation to form sulfentrazone carboxylic acid which is decarboxylated 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 previously determined that, based on the established sulfentrazone tolerances for soybean 

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 comprised 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.
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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 soybeans 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, head and stem [broccoli, Chinese broccoli, 

Brussels sprouts, Chinese (napa) cabbage, Chinese mustard, cauliflower, cavalo broccoli, 

kohlrabi]; Brassica, leafy greens [broccoli raab, Chinese (bok choy) cabbage, collards, kale, 

mizuna, mustard greens, mustard spinach, rape greens]; fruiting vegetables (except curcurbits) 

[eggplant, groundcherry (Physalis spp), pepino, pepper (includes bell pepper, chili pepper, 

cooking pepper, pimento, sweet pepper), tomatillo, tomato]; okra; 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; 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 

stability 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. In one trial conducted in ND 

during the 2002 growing season, flax seed was harvested 123 days 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 processed 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 

phytotoxicity, 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 following two applications (one banded application to soil 
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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, for 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. Since 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 by 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 phytotoxicity, 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 soybeans. As the 1x use rate in soybeans (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 (MRLs) have been established for 

sulfentrazone on the subject crops; therefore, harmonization of MRLs 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 analyses were performed using DEEM-FCIDTM (ver. 2.03). DEEM-FCIDTM

(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 year 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. 
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The acute and chronic analyses assumed tolerance-level residues for all commodities, 100% CT, 

and DEEM(ver. 7.81) default processing factors (as necessary). The analyses also 

incorporated the drinking water estimates provided by EFED. The EDWCs were Tier 1 

estimates for groundwater using the SCI-GROW model and surface water using the FIRST 

model for sulfentrazone and 3-carboxylic 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 analysis, respectively. 

The resulting acute food plus water risk estimates are below HED’s level of concern [<100% of 

the aPAD] at the 95th 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 below HED’s level of concern. The most 

highly 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. Summary of Acute Dietary Exposure and Risk for Sulfentrazone at the 95th Percentile. 1

Population Subgroup aPAD (mg/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 years 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

Females 13-49 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 (mg/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 1.5
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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 (D289349, M. Dow, 15-May-2003). Since that assessment, 

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 by K. Lowe (D364913).

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 exposure 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 developed 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 449722-01; OMA004), 

(3) Loading/Applying Granulars via Push-Type Spreader (ORETF data; MRID 449722-

01; OMA003), and

(4) Loading/Applying 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 Division Science 
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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 described 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 likely because of the intermittent nature of applications by homeowners. Short-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, given 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 Exposuresc

(mg/lb ai) Dose (mg/kg/day) MOE Combined MOEi

Baseline 

Dermald

Baseline 

Inhalationd

Baseline 

Dermale

Baseline 

Inhalationf

Baseline 

Dermalg

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 (60 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 (60 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 + Inhalation 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 previously treated. 
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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 potential 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, subsequently, 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, the 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 usually 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 been 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 year olds); 

 Hand-to-mouth transfer of residues on lawns (3 - <6 year olds);

 Object-to-mouth transfer of residues on lawns (3 - <6 year olds); 

 Incidental 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 with 
Sulfentrazone 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 PODs, 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/cm2)

Application 

Rate

(lb ai/acre)

MOE at Day 0 

(Level of 

Concern = 100)

Combined 

MOE

Adults

Residential Turf (High Contact Activities)

Dermal

14,500

0.375

980

Residential Turf (Mowing) 3,400 4,200 N/A

Golfer 500 14,000

10 - 12 year olds

Residential Turf (Mowing) Dermal 3,400 0.375 2,700 N/A Golfer 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 Granular 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 by the Spray Drift Task Force, a membership of U.S. 

pesticide registrants, and is developing a policy on how to appropriately apply the data and the 

AgDRIFT®computer model to its risk assessments for pesticides applied by air, orchard airblast 

and ground hydraulic methods. 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 Assessments and Risk Characterization

Acute and chronic aggregate risks are made up only of dietary sources; therefore, the exposure 

estimates provided in the dietary exposure analysis represent acute and chronic aggregate 

exposure, respectively. An aggregate cancer risk assessment was not performed because 
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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, handler and post-application residential exposure is expected. It is 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 protective 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 only)

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 similarities in the toxicity endpoints observed between the oral and dermal routes. The shortand 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, only dermal exposure was 

appropriate to aggregate with dietary (food) and water. For young children, due primarily to 

their hand-to-mouth activities, oral (non-dietary) and dermal exposures were aggregated with 

dietary (food) and water. Children can be exposed 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 summarizes the short- and intermediate-term aggregate exposures and risk estimates 

for 1 -2 year olds and adults. Since the aggregate MOEs are ≥ 100, short- and intermediate-term 

aggregate exposures to sulfentrazone are not of concern to HED.
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Table 6.1. Short- and Intermediate-term Aggregate Risk.

Population Target 

MOE

Background Dietary + Incidental 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 

MOEb

Dermal 

Exposure 

(mg/kg/day)

Dermal 

MOEc

Inhalation 

Exposure 

(mg/kg/day)

Inhalation 

MOEd

General 

U.S. 

Population

100

0.001715 N/A 8,000 0.310 320 0.000094 110,000 310

Children 

1-2 years 

old

0.003565

Short-term:

0.0070 1,300

0.146 690 NA NA

Short-term: 450

Intermediateterm:

0.000019

3,900 Intermediate-term: 

590

a. Short-term Incidental Oral Exposure = Hand-to-Mouth exposure + Object-to-Mouth exposure +Soil Ingestion. Intermediateterm Incidental 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 risk 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 by 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 and 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 mechanism 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 (D364913). 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 application 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 Occupational 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 recommends 
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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 PHED (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 only 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 sulfentrazone 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 protective 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, chemicalresistant 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. Long-term exposures are not expected; therefore, a long-
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term assessment was not conducted. The average adult body weight of 60 kg was 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, 

respectively. 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). 
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Table 8.1.1. Agricultural Handler Exposure and Risk for Sulfentrazone.

Crop or Target

Application 

Rate

(lb ai/A)a

Acres 

Treated 

Daily

(acres)b

Unit Exposuresc Dose (mg/kg/day) MOEs Combined MOEsk

Dermal (mg/lb ai) Inhalation 

(ug/lb ai) Dermalg

Inhalationh DermaliInhalationj Baseline 

Dermal + 

Baseline 

Inhalation 

PPE-G 

Dermal + 

Baseline 

Inhalation Baselined

PPE-G

e Baselined 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 0.97 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 Applications
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Table 8.1.1. Agricultural Handler Exposure and Risk for Sulfentrazone.

Crop or Target

Application 

Rate

(lb ai/A)a

Acres 

Treated 

Daily

(acres)b

Unit Exposuresc Dose (mg/kg/day) MOEs Combined MOEsk

Dermal (mg/lb ai) Inhalation 

(ug/lb ai) Dermalg

Inhalationh DermaliInhalationj Baseline 

Dermal + 

Baseline 

Inhalation 

PPE-G 

Dermal + 

Baseline 

Inhalation Baselined

PPE-G

e Baselined 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 0.096 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 contf

: 

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 Sprays 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 19,000
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Table 8.1.1. Agricultural Handler Exposure and Risk for Sulfentrazone.

Crop or Target

Application 

Rate

(lb ai/A)a

Acres 

Treated 

Daily

(acres)b

Unit Exposuresc Dose (mg/kg/day) MOEs Combined MOEsk

Dermal (mg/lb ai) Inhalation 

(ug/lb ai) Dermalg

Inhalationh DermaliInhalationj Baseline 

Dermal + 

Baseline 

Inhalation 

PPE-G 

Dermal + 

Baseline 

Inhalation Baselined

PPE-G

e Baselined 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 0.25 350 0.011 Not applicable 0.35 0.016 Not applicable 0.00051 6200 Not applicable 20,000 4,700 Not applicable

a. Application Rates based on proposed uses on registered labels for sulfentrazone products EPA 379-3189 and 379-3220 and Revised Section B for these 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-sleeved 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 (100 mg/kg/day) / dermal daily dose (mg/kg/day). Level of concern = 100.

j. Inhalation MOE = NOAEL (10 mg/kg/day) / inhalation daily dose (mg/kg/day). Level of concern = 100.

k. Combined MOEs = 1 / ((1/ Dermal MOE) + (1/Inhalation MOE)). 

Table 8.1.2. Agricultural Handler Exposure and Risk for Sulfentrazone – Dry Bulk Fertilizer Preparation.

Exposure Scenario Application 

Ratea

Area 

Treated 

Dailyb

Unit Exposuresc Dose (mg/kg/day) MOE Combined MOEsk

Dermal Inhalation DermalgInhalationh DermaliInhalationj Baseline 

Dermal + 

Baseline 

Inhalation 

PPE-G Dermal 

+ Baseline 

Inhalation 

Baselinee

(mg/lb ai)

PPE-G

f

(mg/lb 

ai)

Baselinee 

(ug/lb ai) Baseline PPE-G Baseline Baseline PPE-G Baseline 

Mixer/Loader

Mixing/Loading Liquids for 

Commercial Impregnation of Dry 

Bulk Fertilizers (PHED)

3.75 lb 

ai/ton 960 tons Eng contd

: 

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 Impregnation of Dry 

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 Onfarm Impregnation of Dry Bulk 

Fertilizers (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 Onfarm Impregnation 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 5,700
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Table 8.1.2. Agricultural Handler Exposure and Risk for Sulfentrazone – Dry Bulk Fertilizer Preparation.

Exposure Scenario Application 

Ratea

Area 

Treated 

Dailyb

Unit Exposuresc Dose (mg/kg/day) MOE Combined MOEsk

Dermal Inhalation DermalgInhalationh DermaliInhalationj Baseline 

Dermal + 

Baseline 

Inhalation 

PPE-G Dermal 

+ Baseline 

Inhalation 

Baselinee

(mg/lb ai)

PPE-G

f

(mg/lb 

ai)

Baselinee 

(ug/lb ai) Baseline PPE-G Baseline Baseline PPE-G Baseline 

Mixing/Loading Dry Flowables for 

Commercial Impregnation 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

Mixing/Loading Dry Flowables for 

Commercial Impregnation 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 Impregnation 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 Impregnation of Dry Bulk 

Fertilizers (PHED)

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. Application Rates based on proposed uses on registered labels for sulfentrazone products 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-sleeved 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 (100 mg/kg/day) / dermal daily dose (mg/kg/day). Level of concern = 1000.

j. Inhalation MOE = NOAEL (14 mg/kg/day) / inhalation daily dose (mg/kg/day). Level of concern = 1000.

k. Combined MOEs = 1 / ((1/ Dermal MOE) + (1/Inhalation MOE)).
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8.2 Occupational Post-application Exposure

Based on the Agency's current practices, a quantitative occupational 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 previously 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 

process of evaluating the SAP report as well as available postapplication inhalation exposure 

data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies 

and procedures, to identify the need for and, subsequently, the way to 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 assessment 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, postapplication 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 postemergent 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 ExpoSAC Policy Number 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.
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Table 8.2.1. Anticipated Post-application Activities and Dermal Transfer Coefficients.

Proposed Crops Policy Crop Group 

Category

Transfer 

Coefficients 

(cm2/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 and Risk for Sulfentrazone.

Crop Grouping/Crop Days after 

Treatment DFR1

(μg/cm2)

Daily Dermal 

Dose2(mg/kg/day) MOE3

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/cm2x 20% DFR after initial treatment.

2. Daily Dermal Dose = [DFR (μg/cm2) 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 REI is 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 REI that 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 new 
Sulfentrazone 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/Analytical Chemistry

Branch/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

Please note that the extended zip code is required for delivery.

9.3 Occupational and Residential Exposure

 None
Sulfentrazone Human-Health Risk Assessment DP# 364882

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Attachment 1: Sulfentrazone Toxicity Profile Tables.

Acute Toxicity Profile – Sulfentrazone.

Guideline 

No.

Study Type MRID(s) Results Toxicity 

Category

870.1100 Acute oral [rat] 41911605 LD50 = 2855 (M & F) mg/kg III

870.1200 Acute dermal [mice] 41911606 LD50 = 711 (M & F) mg/kg III

870.1200 Acute dermal 42286400 LD50 > 2000 mg/kg/day III

870.1300 Acute inhalation [rat] 42471002 4-hour, whole body exposure; LC50 > 

4.13 mg/L III

870.2400 Acute eye irritation 

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

870.2500 Acute dermal irritation 

[rabbit] 41911609 Non-irritating IV

870.2600 Skin sensitization 

[Guinea Pig] 41911610 Not a Dermal Sensitizer N/A

Toxicity Profile for Sulfentrazone

Guideline No./

Study Type

MRID No. 

(year)/Classification/ Doses Results

870.3100

90-Day oral toxicity (rat)

43004601 (1990)

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

Systemic Toxicity NOAEL = 19.9 mg/kg/day in 

males and 23.1 mg/kg/day in females

Systemic 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

Systemic Toxicity NOAEL = 60 mg/kg/day in 

males and 79.8 mg/kg/day in females

Systemic 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-week recovery 

period reversed all the treatment related effects 

except extramedullary hematopoiesis; however 

severity was reduced.
Sulfentrazone Human-Health Risk Assessment DP# 364882

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Toxicity Profile for Sulfentrazone

Guideline No./

Study Type

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

Systemic Toxicity NOAEL= 28 mg/kg/day for 

males and

females

Systemic 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 

volume, 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

Systemic and Dermal Toxicity NOAEL = 1000 

mg/kg/day

(Highest Dose Tested or HDT)

Systemic 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

implantations and percentage of live fetuses, 

increase in the percentage of early resorptions, and 

decreased fetal body weights.

Supplemental study to the 1992 DevelopmentalToxicity Study in Rats (MRID 42932104)
Sulfentrazone Human-Health Risk Assessment DP# 364882

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Toxicity Profile for Sulfentrazone

Guideline No./

Study Type

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; increased 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

Developmental 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)

Acceptable/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 bodyweight 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

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Toxicity Profile for Sulfentrazone

Guideline No./

Study Type

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

Systemic/Developmental Toxicity NOAEL =20 (F)

mg/kg/day

Systemic/Developmental Toxicity LOAEL = 51 (F)

mg/kg/day, (F1 females), based on decrease in premating body-weight gain (10%)

Offspring and Reproductive Toxicity NOAEL = 16

mg/kg/day (M/F) mg/kg/day

Offspring and Reproductive Toxicity LOAEL 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 supports 

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

Systemic toxicity NOAEL = 24.9/29.6 mg/kg/day 

for males/and females

Systemic 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

Systemic toxicity NOAEL = 93.9 mg/kg/day for 

males and

116.9 mg/kg/day for females

Systemic toxicity LOAEL = 160.5 mg/kg/day for 

males and

198.0 mg/kg/day for females, based on dose-related 

decreases in hemoglobin and hematocrit by study 

termination.

No evidence of carcinogenicity.

870.4300

Combined 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

Systemic toxicity NOAEL = 40 mg/kg/day for 

males and

36.4 mg/kg/day for females

Systemic toxicity LOAEL = 82.8 mg/kg/day for 

males and 67 mg/kg/day for females, based on 

dose-related decreased body 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.
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Toxicity Profile for Sulfentrazone

Guideline No./

Study Type

MRID No. 

(year)/Classification/ Doses Results

870.5100

Gene Mutation: Ames 

assay

Gene Mutation: HGPRT

41911611 (1986)

Acceptable/Guideline

Salmonella typhimurium 

strains

TA1535, TA1538, TA1537, 

TA98 and TA100 were 

exposed to Sulfentrazone 

Technical (95.5%) at 

concentrations of 100-10,000 

ug/plate with or without S9 

activation (both trials).

No evidence of compound-induced cytotoxicity 

was evident either in presence or in absence of S9 

activation. The positive controls induced the 

expected mutagenic responses in the appropriate 

tester 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 nonactivated 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 

precipitating 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

Groups 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. 

Cyclophosphamide 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 dead: total 

implants, 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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Toxicity Profile for Sulfentrazone

Guideline No./

Study Type

MRID No. 

(year)/Classification/ Doses Results

870.6200 Acute 

Neurotoxicity Study

43345405 (1994)

Acceptable/Guideline

0, 250, 750, & 2000 mg/kg

Systemic Toxicity NOAEL = 250 mg/kg/day

Systemic 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 

motor 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 SpragueDawley 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 nonradioactive 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 

was 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 De Castro, et al., (2007)

Acceptable/non-guideline

0, 25, or 50 mg/kg bw/day

Dose-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.