Page 1 of 57

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Date: 05-JUN-2014

SUBJECT: Sulfentrazone – Preliminary Human-Health Risk Assessment for Registration 

Review and the Risk Assessment for the Section 3 Registration Request for a 

New Use on Apples 

PC Code: 129081 DP Barcode: D410365

Decision Nos.: 476747, 483232 Registration Nos.: 279-3370, 279-3189, & 279-3220

Petition No.: 3E8202 Regulatory Action: Section 3 and Registration Review 

Risk Assessments

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: George F. Kramer, Ph.D., Senior Chemist

Kelly M. Lowe, Environmental Scientist

Anwar Y. Dunbar, Ph.D., Pharmacologist

Risk Assessment Branch 1 (RAB1)

Health Effects Division (HED; 7509P)

Through: Charles W. Smith III, Branch Chief

RAB1/HED (7509P)

To: Laura Nollen/Barbara Madden, RM 05

Registration Division (RD, 7505P)

and

Christina Scheltema

Pesticide Reevaluation Division (7509P)

As part of Registration Review, the Pesticide Re-evaluation Division (PRD) of OPP has 

requested that HED evaluate the hazard and exposure data and conduct occupational and 

residential exposure assessments, as needed, to estimate the risk to human health that will result 

from the currently registered uses of pesticides. This memorandum serves as HED’s Preliminary

Registration Review risk assessment of the dietary, occupational and residential handler, postapplication exposure, and aggregate risk from the registered/proposed uses of sulfentrazone. 

In addition, the Registration Division (RD) requested that HED conduct an exposure and risk 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 2 of 57

assessment for the proposed new use of sulfentrazone on apples. This memorandum provides 

HED’s human-health risk assessment conducted in support of this request to establish tolerances 

for residues of sulfentrazone and its metabolites HMS (N-(2,4-dichloro-5-(4-(difluoromethyl)-

4,5-dihydro-3-hydroxymethyl-5-oxo-1H-1,2,4-triazol-1-yl)phenyl)methanesulfonamide) and 

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

yl)phenyl)methanesulfonamide in/on apples.

A summary of the findings and an assessment of human risk resulting from the registered and 

proposed uses are provided in this document. The risk assessment, dietary risk assessment, and 

residue chemistry review were provided by George Kramer (RAB1), the occupational/residential 

exposure and risk assessment was provided by Kelly Lowe (RAB1), the hazard characterization 

was provided by Anwar Dunbar (RAB1), and the drinking water assessment was provided by 

Michael Barrett of the Environmental Fate and Effects Division (EFED).
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 3 of 57

Table of Contents

1.0 Executive Summary ........................................................................................................................................5

2.0 Recommendations...........................................................................................................................................7

2.1 Data Deficiencies/Data Needs.............................................................................................................8

2.2 Tolerance Considerations....................................................................................................................8

2.2.1 Enforcement Analytical Method..............................................................................................................8

2.2.2 Recommended Tolerances.......................................................................................................................8

2.2.3 Revisions to Petitioned-For Tolerances.................................................................................................10

2.2.4 International Harmonization ..................................................................................................................11

2.3 Label Recommendations...................................................................................................................11

3.0 Ingredient Profile...........................................................................................................................................11

3.1 Chemical Identity ..............................................................................................................................11

3.2 Physical/Chemical Properties............................................................................................................12

3.3 Use Pattern ........................................................................................................................................12

3.4 Anticipated Exposure Pathways........................................................................................................17

3.5 Consideration of Environmental Justice............................................................................................17

4.0 Hazard Characterization and Dose-Response Assessment............................................................................17

4.1 Toxicology Studies Available for Analysis.......................................................................................18

4.2 Absorption, Distribution, Metabolism, & Excretion (ADME)..........................................................18

4.2.1 Dermal Absorption ................................................................................................................................18

4.3 Toxicological Effects ........................................................................................................................18

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ..........................................................20

4.4.1 Completeness of the Toxicology Database ............................................................................................20

4.4.2 Evidence of Neurotoxicity .....................................................................................................................20

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal.........................................20

4.4.4 Residual Uncertainty in the Exposure Database ....................................................................................20

4.5 Toxicity Endpoints and Point of Departure Selections......................................................................21

4.5.1 Dose-Response Assessment...................................................................................................................21

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment .......................................23

4.5.3 Cancer Classification and Risk Assessment Recommendation .............................................................23

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human-Health Risk Assessment ...23

4.6 Endocrine Disruptor Screening Program...........................................................................................25

5.0 Dietary Exposure and Risk Assessment ........................................................................................................26

5.1 Metabolite/Degradate Residue Profile...............................................................................................26

5.1.1 Summary of Plant and Animal Metabolism Studies..............................................................................26

5.1.2 Summary of Environmental Degradation ..............................................................................................26

5.1.3 Comparison of Metabolic Pathways......................................................................................................27

5.1.4 Residues of Concern Summary and Rationale.......................................................................................27

5.2 Food Residue Profile .........................................................................................................................27

5.3 Drinking Water Residue Profile ........................................................................................................28

5.4 Dietary (Food + Drinking Water) Risk Assessment..........................................................................29

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ................................................................29

6.1 Residential Handler Exposure/Risk Estimates ..................................................................................30

6.2 Residential Post-application Exposure/Risk Estimates .....................................................................32

6.3 Residential Risk Estimates for Use in Aggregate Assessment ..........................................................32

6.4 Spray Drift.........................................................................................................................................33

6.5 Residential Bystander Post-Application Inhalation Exposure...........................................................34

7.0 Aggregate Exposure/Risk Characterization...................................................................................................34

7.1 Acute Aggregate Risk .......................................................................................................................34

7.2 Short- and Intermediate-Term Aggregate Risk .................................................................................34

7.3 Chronic Aggregate Risk ....................................................................................................................35

7.4 Cancer Aggregate Risk......................................................................................................................36

8.0 Cumulative Exposure/Risk Characterization.................................................................................................36

9.0 Occupational Exposure/Risk Characterization..............................................................................................36

9.1 Handler Risk Assessment..................................................................................................................36

9.2 Post-Application Risk Assessment....................................................................................................41

9.2.1 Inhalation Post-Application Risk Assessment .......................................................................................41

9.2.2 Dermal Post-Application Risk Assessment ...........................................................................................41
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 4 of 57

10.0 References.....................................................................................................................................................42

Appendix A. Toxicology Profile and Executive Summaries......................................................................................43

Appendix B. Methodologies for HEC Calculations....................................................................................................49

Appendix C. Physical/Chemical Properties................................................................................................................54

Appendix D. International Residue Limits.................................................................................................................55
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 5 of 57

1.0 Executive Summary

Sulfentrazone is an aryl triazolinone herbicide used to control a variety of broadleaf weeds. 

Sulfentrazone acts by the same mechanism as the diphenyl ether herbicides in which membrane 

disruption is initiated by the inhibition of protoporphyrinogen oxidase (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.

This preliminary risk assessment provides information to support the Registration Review of 

sulfentrazone, and addresses the exposures and risk estimates associated with all currently 

registered and proposed uses. Since the last risk assessment, new data have been submitted and 

policies have changed. This document incorporates changes made to the selected endpoints, 

toxicological points of departure (PODs), exposure and risk estimates, recommended tolerances, 

and the potential for spray-drift exposure. All data requirements previously addressed during the 

scoping process have been satisfied (K. Lowe, D369064, 09/09/2009). In addition, this document 

evaluates the petition submitted by Interregional Research Project No. 4 (IR-4; PP# 3E8202) that 

proposes new tolerances for residues of sulfentrazone and its metabolites on apples.

Hazard Assessment: Results of mammalian toxicity studies were consistent with PPO inhibition, 

given that PPO is an important enzyme in the heme synthetic pathway in mammals. 

Specifically, toxicity reflective of disruption of heme synthesis (hematotoxicity) was observed in 

mice, rats, and dogs, and this was seen at about the same dose levels in the oral studies 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 caused developmental effects via the oral and dermal routes of exposure. 

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 

in the absence of maternal toxicity. In the two-generation reproduction study in rats, offspring 

effects, such as decreased body weights and decreased litter survival were observed at doses that 

were maternally toxic (decreased body weight during gestation in both generations).

In a route-specific 28-day dermal toxicity study in adult rabbits, there were no effects up the 

highest dose tested. In the route-specific 26-day inhalation study, there were portal-of-entry

effects in the nasal passage and systemic effects, including decreased body weights and changes 

in numerous hematological parameters.

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

formation due to treatment with sulfentrazone and genotoxicity studies were all negative.

Food Quality Protection Act (FQPA) Safety Factor (SF) Decision: The sulfentrazone risk 

assessment team concludes that the 10X FQPA SF should be reduced to 1X since the toxicology

database is adequate for assessment of the registered and proposed uses, selected endpoints are 

protective of the effects seen in the neurotoxicity studies as well as the increased susceptibility to 

offspring observed in developmental studies, and the conservative nature of the dietary and 

residential exposure analyses are unlikely to underestimate exposure [tolerance-level residues, 

100% crop treated (%CT); use of 2012 Residential Standard Operating Procedures (SOPs)].
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 6 of 57

Dose Response Assessment: The two-generation reproductive toxicity study in rats [no-observed 

adverse-effect level (NOAEL) = 14 mg/kg/day] was selected for assessment of acute dietary

(females 13-49 years old), chronic dietary, and incidental oral exposure scenarios. The acute 

neurotoxicity (ACN) study (NOAEL = 250 mg/kg/day) was selected for assessment of acute 

dietary (all populations excluding females 13-49 years old) exposure. The dermal developmental 

toxicity study in rats (NOAEL = 100 mg/kg/day) was selected for assessment of dermal exposure 

(all durations). The route-specific 26-day inhalation study in rats (NOAEL is 0.256 mg/L) was 

selected for assessment of inhalation exposure (all durations). For all exposure scenarios except 

inhalation, a 100X uncertainty factor was applied [10X interspecies extrapolation; 10X for 

intraspecies variation; 1X FQPA SF (when applicable)]. For inhalation exposure scenarios, a 30X

uncertainty factor was applied [3X interspecies extrapolation; 10X for intraspecies variation; 1X

FQPA SF (when applicable)].

Dietary Risk Estimates (Food + Drinking Water): Acute and chronic aggregate dietary (food and 

drinking water) exposure and risk assessments were conducted using the Dietary Exposure 

Evaluation Model - Food Consumption Intake Database (DEEM-FCID, ver. 3.16) which 

incorporates consumption data from United States Department of Agriculture (USDA) National 

Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA; 2003-

2008). The acute and chronic analyses assumed tolerance-level residues, 100% %CT, DEEM 

(ver. 7.81) default processing factors, and modeled drinking water estimates. The resulting acute 

and chronic dietary risk estimates are not of concern to HED, and the subgroups with the greatest 

risk estimates utilized ≤7% of the acute population-adjusted dose (aPAD; females 13-49 years 

old) and ≤7% of the chronic population-adjusted dose (cPAD; children 1-2 years old), 

respectively. 

Residential (Non-Occupational) Exposure and Risk Assessment: The proposed use on apples 

will not result in residential exposure; however, there are currently registered turf uses (e.g., 

residential turf, golf courses) that were assessed as part of Registration Review. All dermal and 

inhalation exposure risk estimates for residential handlers are not of concern [i.e., margins of 

exposure (MOEs) were ≥ 100 for dermal and ≥ 30 for inhalation risk] at baseline for all 

scenarios; MOEs were ≥ 560 for dermal and ≥ 1200 for inhalation risk. All residential postapplication dermal risk estimates are also not of concern (i.e., MOEs ≥ 100); all MOEs were ≥ 

610 for adults and ≥ 360 for children.

A quantitative spray drift assessment for sulfentrazone is not required. The turf post-application 

MOEs are protective for any potential exposures related to spray drift for sulfentrazone.

Aggregate-Risk Estimates: In accordance with FQPA, HED must consider and aggregate 

pesticide exposures and risks from three major sources: food, drinking water, and residential 

exposures. Acute, chronic, short-, and intermediate-term aggregate assessments were included in 

this risk assessment. An aggregate cancer risk assessment was not performed because 

sulfentrazone is not considered to be a carcinogen. Acute and chronic aggregate risks are made 

up only of dietary sources; therefore, the exposure estimates provided in the dietary exposure 

analyses represent acute and chronic aggregate exposure, respectively. Short- and intermediateterm aggregate risks are made up of dietary and non-dietary sources of exposure. Since 

sulfentrazone is used on turf, residential handler and post-application exposures are expected. 

Short-term exposures exist for adults and children from the registered turf application use. In 

addition, intermediate-term exposures exist for children from incidental soil ingestion. All 

aggregate sulfentrazone risk estimates are not of concern to HED. 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 7 of 57

Occupational Exposure and Risk Assessment: A quantitative assessment of occupational 

exposure has been conducted for all of the registered and proposed uses. The occupational 

handler exposure and risk estimates indicate that the short- and intermediate-term dermal and 

inhalation MOEs are not of concern to HED (i.e., MOEs were ≥ 100 for dermal and ≥ 30 for 

inhalation risk), as long as gloves are worn for the highest application rate for mixing/loading 

liquids and dry flowables for aerial application to high-acreage crops. Occupational postapplication dermal exposure and risk estimates were assessed, and are greater than the level of 

concern (LOC) of 100 on the day of application (MOEs = 430 to 8,200). Since the postapplication assessment is not a concern on Day 0 (12 hours following application), the restrictedentry interval (REI) is based on the acute toxicity of sulfentrazone technical material. 

Sulfentrazone is classified as acute Toxicity Category III for acute oral, acute dermal, and acute 

inhalation toxicity. It is classified as Toxicity Category III for eye irritation potential and 

Toxicity Category IV for skin irritation potential. It is not a dermal sensitizer. Therefore, the 

acute toxicity categories for this chemical require a 12-hour REI under 40 CFR 

156.208(c)(2)(iii). 

Based on the Agency's current practices, a quantitative non-cancer occupational post-application 

inhalation exposure assessment was not performed for sulfentrazone at this time. If new policies 

or procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for sulfentrazone.

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.”

Review of Human Research: This risk assessment relies in part on data from studies in which adult 

human subjects were intentionally exposed to a pesticide or other chemical. These data, which 

include studies from the Pesticide Handlers Exposure Database (PHED) 1.1, the Agricultural 

Handler Exposure Task Force (AHETF) database, and the Agricultural Reentry Task Force (ARTF)

database are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that review, and 

(3) are compliant with applicable ethics requirements. For certain studies, the ethics review may

have included review by the Human Studies Review Board. Descriptions of data sources, as well as 

guidance on their use, can be found at the following Agency websites: 

http://www.epa.gov/pesticides/science/handler-exposure-data.html and http://www.epa.gov/pesticides/science/post-appexposure-data.html. 

2.0 Recommendations

HED has examined the toxicology and residue chemistry databases for sulfentrazone. Pending 

resolution of the deficiencies outlined below, there are no other residue chemistry, residential, 

occupational, or toxicology data deficiencies that would preclude the continuation of permanent 

tolerances for residues of sulfentrazone and its metabolites as outlined in Table 2.2.2.1. 

For the proposed use on apples, HED concludes that the residue chemistry database supports the 

establishment of the permanent tolerance listed in Table 2.2.2.1. 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 8 of 57

2.1 Data Deficiencies/Data Needs

860.1650 Submittal of Analytical Reference Standards

Analytical standards for sulfentrazone (expiration date 7/1/15) and its metabolites DMS 

(expiration date 8/1/17) and HMS (expiration date 8/31/18) are currently available at the EPA 

National Pesticide Standards Repository (personal communication with Theresa Cole, 4/21/14). 

However, as the existing stocks are depleted, the Repository has requested that the registrant 

provide additional amounts of sulfentrazone (5 g) and HMS (3 g). They should be sent to the 

Analytical Chemistry Lab, which is located at Fort Meade, to the attention of either Theresa Cole 

or Thuy Nygen at the following address:

USEPA

National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

(Note that the mail will be returned if the extended zip code is not used.)

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

There is an adequate residue analytical method for the purposes of tolerance enforcement. A gas 

chromatography (GC) method for the determination of sulfentrazone and its metabolites DMS and 

HMS was submitted with a petition for a sulfentrazone tolerance for residues in/on soybeans (PP# 

4F04407). A petition method validation (PMV) was successfully completed by the Agency’s 

Analytical Chemistry Laboratory (ACL). The limit of quantitation (LOQ) and limit of detection 

(LOD) were determined to be 0.05 ppm and 0.005-0.025 ppm, respectively. The method has been 

forwarded to the Food and Drug Administration (FDA) for inclusion in the Pesticide Analytical 

Methods Vol. II (PAM II).

The data requirements for multiresidue methods (MRMs) are fulfilled. The FDA MRMs are not 

suitable as enforcement methods since sulfentrazone residues of concern were not successfully 

recovered by the FDA MRMs.

Samples of raw agricultural and processed commodities from the apple studies were analyzed for 

residues of sulfentrazone and its metabolites DMS and HMS using a liquid chromatograph equipped 

with tandem mass spectrometers (LC/MS/MS) method. The validated LOQ was 0.025-0.05 ppm for 

each analyte. These methods are adequate for data collection based on acceptable method validation 

and concurrent recovery data.

2.2.2 Recommended Tolerances

Permanent tolerances have been established in 40 CFR §180.498 for the combined residues of the 

free and conjugated forms of sulfentrazone, including its metabolites and degradates in/on various 

raw agricultural commodities ranging from 0.05 ppm to 0.60 ppm.

Table 2.2.2.1 is a summary of the proposed and HED-recommended tolerances for residues of 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 9 of 57

sulfentrazone per se. 

Table 2.2.2.1. Tolerance Summary for Sulfentrazone (40 CFR §180.498).

Commodity

Proposed / 

Established 

Tolerance 

(ppm)

HEDRecommended 

Tolerance (ppm)

Comments

(a)(1) General. Tolerances are established for the combined residues of the free and conjugated forms of sulfentrazone, 

including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels 

specified below is to be determined by measuring only the sum of 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 metabolite HMS (N-(2,4-dichloro5-(4-(difluoromethyl)-4,5-dihydro-3-hydroxymethyl-5-oxo-1H-1,2,4-triazol-1-yl)phenyl)methanesulfonamide, calculated 

as the stoichiometric equivalent of sulfentrazone in or on the following commodities.

Soybean, seed 0.05

(2) Tolerances are established for the combined residues of the free and conjugated forms of sulfentrazone, including its 

metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified 

below is to be determined by measuring only the sum of sulfentrazone (N-[2,4-dichloro-5-[4-(difluoromethyl)-4,5-dihydro3-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-triazol-1-yl)phenyl)methanesulfonamide) and DMS (N-

(2,4-dichloro-5-(4-(difluoromethyl)-4,5-dihydro-5-oxo-1H-1,2,4-triazol-1-yl)phenyl)methanesulfonamide, calculated as 

the stoichiometric equivalent of sulfentrazone in or on the following commodities.

Apple 0.15 Proposed new use (PP# 3E8202)

Asparagus 0.15

Berry and small fruit, group 13-07 0.15

Brassica, head and stem, 

subgroup 5A 0.20

Brassica, leafy greens, subgroup 

5B 0.40

Corn, field, forage 0.20

Corn, field, grain 0.15

Corn, field, stover 0.30

Flax 0.15 Correct commodity definition to “Flax, seed”

Fruit, citrus, group 10-10 0.15

Horseradish 0.20

Melon, subgroup 9A 0.15

Nut, tree, group 14 0.15 Update crop group to “Nut, tree, group 14-12”

Pea and bean, dried shelled, 

except soybean, subgroup 6C 0.15

Pea, succulent 0.15

Peanut 0.20

Peanut, meal 0.40

Peppermint, tops 0.30

Pistachio 0.15 none

Delete, pistachio is member of Nut, tree, group 14-

12

Rhubarb 0.15

Spearmint, tops 0.30

Sugarcane, cane 0.15

Sugarcane, molasses 0.20

Sunflower subgroup 20B 0.20

Turnip, roots 0.15

Turnip, tops 0.60

Vegetable, fruiting, group 8-10 0.15
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 10 of 57

Table 2.2.2.1. Tolerance Summary for Sulfentrazone (40 CFR §180.498).

Commodity

Proposed / 

Established 

Tolerance 

(ppm)

HEDRecommended 

Tolerance (ppm)

Comments

Vegetable, soybean, succulent 0.15

Vegetable, tuberous and corm, 

subgroup 1C 0.15

(c) Tolerances with regional registrations. Tolerances with regional registration are established for the combined residues 

of the free and conjugated forms of sulfentrazone, including its metabolites and degradates, in or on the commodities in the 

table below. Compliance with the tolerance levels specified below is to be determined by measuring only the sum of 

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-triazol-1-yl)phenyl)methanesulfonamide) and DMS (N-(2,4-dichloro-5-(4-

(difluoromethyl)-4,5-dihydro-5-oxo-1H-1,2,4-triazol-1-yl)phenyl)methanesulfonamide, calculated as the stoichiometric 

equivalent of sulfentrazone in or on the following commodities.

Bean, lima, succulent 0.15

Cowpea, succulent 0.15

Wheat, forage 0.50

Wheat, grain 0.15

Wheat, hay 0.30

Wheat, straw 1.5

(d) Indirect or inadvertent residues. Tolerances are established for inadvertent and indirect combined residues of the free 

and conjugated forms of sulfentrazone, including its metabolites and degradates, in or on the commodities in the table 

below. Compliance with the tolerance levels specified below is to be determined by measuring only the sum of 

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-triazol-1-yl)phenyl)methanesulfonamide) and DMS (N-(2,4-dichloro-5-(4-

(difluoromethyl)-4,5-dihydro-5-oxo-1H-1,2,4-triazol-1-yl)phenyl)methanesulfonamide, calculated as the stoichiometric 

equivalent of sulfentrazone in or on the following commodities when present therein as a result of the application of 

sulfentrazone to growing crops.

Grain, cereal (excluding sweet 

corn), Hulls 0.30

Grain, cereal, forage, fodder and 

straw, group 16, except sweet 

corn; forage

0.2 0.20

Correct number of significant figures to be 

consistent with HED policy

Grain, cereal, forage, fodder and 

straw, group 16, except sweet 

corn; hay

0.2 0.20

Grain, cereal, forage, fodder and 

straw, group 16, except sweet 

corn; stover

0.1 0.10

Grain, cereal, forage, fodder and 

straw, group 16, except sweet 

corn; straw

0.6 0.60

Grain, cereal, group 15, except 

sweet corn 0.1 0.10

Grain, cereal, group 15, except 

sweet corn; bran 0.15

2.2.3 Revisions to Petitioned-For Tolerances

Based on the proposed uses and the submitted data, no revisions to petitioned-for tolerances are 

required. 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 11 of 57

2.2.4 International Harmonization

There are no Codex maximum residue limits (MRLs) established for residues of sulfentrazone. 

The U.S. residue definitions are harmonized with Canada. For those commodities which the US 

and Canada have in common, the tolerance values are harmonized (asparagus, flaxseeds, 

horseradish roots, dry peas and beans, peppermint tops, spearmint tops, sunflower seeds, and 

cereal grain group 15). For a summary of U.S. tolerances and international MRLs, refer to 

Appendix D.

2.3 Label Recommendations

Occupational/Residential:

 For several occupational handler scenarios, chemical-resistant gloves are necessary to 

achieve MOEs greater than the LOC. PRD should ensure the appropriate type of glove is 

listed as required on the label.

3.0 Ingredient Profile

3.1 Chemical Identity

The chemical structure and nomenclature of sulfentrazone and its metabolites are presented in 

Table 3.1.1. 

Table 3.1.1. Nomenclature for Sulfentrazone and its Metabolites.

Chemical structure

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-triazol-1-

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

Common name 3-desmethyl sulfentrazone; DMS

Cl

Cl

HN

SO2CH3

N

N

N

O

CH3

CHF2

Cl

Cl

HN

SO2CH3

N

N

N

O

CHF2
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 12 of 57

Table 3.1.1. Nomenclature for Sulfentrazone and its Metabolites.

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

Common name 3-hydroxymethyl sulfentrazone; HMS

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

triazol-1-yl)phenyl)methanesulfonamide

3.2 Physical/Chemical Properties

In general, sulfentrazone is persistent and mobile. It has a 545-day aerobic soil half-life1and an 

average Koc coefficient of 45 mL/g. Additionally, it has a strong potential to leach into 

groundwater, as indicated in four completed small-scale prospective ground-water monitoring 

studies, and to move offsite to surface water. It has a low vapor pressure of 8x10-10 mm Hg. A 

detailed description of the physicochemical properties of sulfentrazone is provided in Appendix 

B. 

3.3 Use Pattern

There are numerous end-use product labels registered with sulfentrazone as the active ingredient. 

These include liquid, dry-flowable, and granular formulations. The labeled use sites include 

various agricultural crops, Christmas tree farms, golf courses, seedling nurseries, landscape 

ornamentals, non-crop use sites (such as railroad, highway, roadside, pipeline, and utility rightsof-way and industrial areas), residential/commercial turf, and sod farms. Most of the uses are 

soil-directed, and are applied via either aerial, chemigation, groundboom or handheld equipment. 

Several labels also allow for application of liquid formulations via dry-bulk fertilizer. The 

maximum application rate for agricultural crops and turf is 0.375 lb ai/A (0.0086 lb ai/1000 ft2or 

0.019 lb ai/gal). 

The proposed use on apples is as a soil-directed application via groundboom. The maximum rate 

allowed is 0.375 lb ai/A. One broadcast application can be made per year, and up to two banded 

applications directed to the base of tree trunk can be made 60 days apart. The REI for all the 

proposed uses is 12 hours. Based on the proposed and registered use patterns, it has been 

determined that the potential exposure scenarios that will need to be assessed include short- and 

intermediate-term occupational and residential exposures (handler and post-application).

A summary of the registered and proposed labels are included in Table 3.3.1 below. All dry bulk 

fertilizer applications have been assessed at a maximum rate of 3.75 lb ai/ton fertilizer and/or 

0.375 lb ai/A. 

Table 3.3.1. Summary of Registered and Proposed Uses for Sulfentrazone.

 

1

90th percentile upper confidence interval of the mean half-life.

Cl

Cl

HN

SO2CH3

N

N

N

O

CHF2

OH
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 13 of 57

Crop/Use Site

Application Timing 

and Type of 

Application

Registered 

Formulations

Maximum 

Application Rate

Personal-protective Equipment 

(PPE), Restricted-entry 

Interval (REI), and Preharvest 

Interval (PHI)

Apples (new use) Soil directed; 

Groundboom Liquid and DF 0.375 lb ai/A

PPE = Long-sleeve shirt, long 

pants, chemical-resistant (CR)

gloves, shoes plus socks; REI = 

12 hours; PHI = 14 days

Asparagus

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.375 lb ai/A

PPE = Single layer (SL) w/ CR

gloves; REI = 12 hr; PHI = 14 

days

Biofuel crops 

(Napiergrass, Miscane, 

Napiergrass cross; SLN)

Soil directed; aerial or 

groundboom Liquid and DF 0.375 lb ai/A PPE = SL w/CR gloves; REI = 12 hr

Berries (Crop group 13-07)

Soil directed; 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.375 lb ai/A PPE = SL w/CR gloves; REI = 12 

hr; PHI = 3 days

Brassica, head and stem

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.375 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

Brassica, leafy greens

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.2 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

Cabbage

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.375 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

Christmas Tree Farms

Soil directed; 

groundboom/tractordrawn spreader; 

handheld 

Liquid 

0.0375 lb ai/gal, 

0.0086 lb ai/1000 ft2

or 0.375 lb ai/A

PPE = SL w/CR gloves (some 

labels only list waterproof 

gloves); REI = 12 hr (some labels 

G 0.375 lb ai/A do not have REI listed)

Citrus fruit

Soil directed; 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.375 lb ai/A PPE = SL w/CR gloves; REI = 12 

hr; PHI = 3 days

Corn

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.25 lb ai/A

PPE = SL w/CR gloves; REI = 12 

- 24 hr; PHI = NA (preemergence 

only)

Cowpeas, succulent

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.19 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

Dry shelled peas and beans

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.25 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

Edamame

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.19 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

Fallow cropping systems

Applied prior to 

planting, early preplant, 

or preemergence; aerial 

or groundboom; dry 

bulk fertilizer

Liquid and DF 0.25 lb ai/A PPE = SL w/CR gloves; REI = 12 

hr

Flax

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

Liquid and DF 0.375 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 14 of 57

Table 3.3.1. Summary of Registered and Proposed Uses for Sulfentrazone.

Crop/Use Site

Application Timing 

and Type of 

Application

Registered 

Formulations

Maximum 

Application Rate

Personal-protective Equipment 

(PPE), Restricted-entry 

Interval (REI), and Preharvest 

Interval (PHI)

fertilizer

Fruiting Vegetables (except 

cucurbits) and Okra

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.375 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

Golf Course Fairways and 

Roughs

Aerial, handheld or 

groundboom/tractordrawn spreader

DF

0.375 lb ai/A, 0.008 

lb ai/1000 ft2or 

0.019 lb ai/gal PPE = SL w/CR gloves (some 

labels only list waterproof 

gloves); REI = 12 hr (some labels 

do not have REI listed)

G

0.0086 lb ai/1000 ft2

or 0.375 lb ai/A Liquid

Grapes 

Soil directed; 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.375 lb ai/A PPE = SL w/CR gloves; REI = 12 

hr; PHI = 3 days

Hardwood seedling 

nurseries

Soil directed; 

groundboom/tractordrawn spreader; 

handheld 

Liquid 0.0086 lb ai/1000 ft2

or 0.375 lb ai/A

PPE = SL w/CR gloves (some 

labels only list waterproof 

gloves); REI = 12 hr (some labels 

do not have REI listed) G 0.375 lb ai/A

Horseradish

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.25 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

Landscape ornamentals 

(Container, Field grown 

Ornamental plantings)

Groundboom/tractordrawn spreader or 

handheld

G or Liquid

0.0375 lb ai/gal, 

0.0086 lb ai/1000 ft2

or 0.375 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr

Lima beans

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.19 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

Melons

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.25 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

Mint

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.375 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA 

(preemergence/dormant only)

Nongrass Animal Feeds 

Crop Group 18*

(Alfalfa; bean, velvet; 

clover (Trifolium, 

Melilotus); kudzu; 

lespedeza; lupin; sainfoin; 

trefoil; vetch; vetch, crown; 

vetch, milk)

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.375 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = forage and hay may be 

harvested or grazed 21 days after 

application, and crop grown for 

seed may be harvested as early as 

41 days after application.

Peanuts

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.25 lb ai/A

PPE = SL w/CR gloves; REI = 12 

- 24 hr; PHI = NA (preemergence 

only)

Peppers (SLN) Soil directed; 

groundboom Liquid 0.18 lb ai/A

PPE = SL w/ CR gloves and 

protective eyewear (goggles or 

face shield); REI = NA 

(preemergence only)
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 15 of 57

Table 3.3.1. Summary of Registered and Proposed Uses for Sulfentrazone.

Crop/Use Site

Application Timing 

and Type of 

Application

Registered 

Formulations

Maximum 

Application Rate

Personal-protective Equipment 

(PPE), Restricted-entry 

Interval (REI), and Preharvest 

Interval (PHI)

Potato

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.25 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

Railroad, Highway, 

Roadside, Pipeline and 

Utility Rights of-Way, 

Industrial Areas,

Fence Rows, and Other 

listed Non-crop Sites

Aerial, handheld or 

groundboom/tractordrawn spreader

DF

0.375 lb ai/A, 0.008 

lb ai/1000 ft2or 

0.019 lb ai/gal PPE = SL w/CR gloves (some 

labels only list waterproof 

gloves); REI = 12 hr (some labels 

do not have REI listed)

G 0.0375 lb ai/gal, 

0.0086 lb ai/1000 ft2

Liquid or 0.375 lb ai/A

Residential/Commercial 

Turf

Handheld or 

groundboom/tractordrawn spreader

DF

0.375 lb ai/A, 0.008 

lb ai/1000 ft2or 

0.019 lb ai/gal

REI = 12 hr; PPE = SL w/ 

waterproof gloves

DF in WSP

0.0066 lb ai/1000 ft2

OR 0.287 lb ai/A or 

0.0033 lb ai/gallon

REI = 12 hr; PPE = SL w/ 

waterproof gloves

G

0.0086 lb ai/1000 ft2

or 0.375 lb ai/A; 

max % ai = 0.4%

REI = 12 hr; PPE = SL w/ 

waterproof gloves

Aerial or groundboom, 

handheld Liquid 0.0086 lb ai/1000 ft2or 0.375 lb ai/A

REI = 12 -48 hr; PPE = SL w/ 

waterproof gloves; some labels 

require CR gloves; some labels 

require CR apron when 

mxing/loading

Handheld RTU 0.001 lb ai/1000 ft2 Residential labels; no PPE or REI 

listed

Rhubarb

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.25 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

Sod Farms

Aerial, groundboom; 

chemigation DF

0.375 lb ai/A, 0.008 

lb ai/1000 ft2or 

0.019 lb ai/gal PPE = SL w/CR gloves (some 

labels only list waterproof 

gloves); REI = 12 hr (some labels 

do not have REI listed)

Tractor-drawn spreader G

0.0086 lb ai/1000 ft2

or 0.375 lb ai/A Aerial, groundboom; 

chemigation; dry bulk 

fertilizer

Liquid

Soybeans

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.375 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

Strawberry

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.375 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

Succulent peas

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.19 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

Sugarcane

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.375 lb ai/A PPE = SL w/CR gloves; REI = 12 

hr; PHI = 120 days

Sunflower

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

Liquid and DF 0.25 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 16 of 57

Table 3.3.1. Summary of Registered and Proposed Uses for Sulfentrazone.

Crop/Use Site

Application Timing 

and Type of 

Application

Registered 

Formulations

Maximum 

Application Rate

Personal-protective Equipment 

(PPE), Restricted-entry 

Interval (REI), and Preharvest 

Interval (PHI)

fertilizer

Tobacco

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.375 lb ai/A PPE = SL w/CR gloves; REI = 12 

hr; PHI = 14 days

Tree nuts

Soil directed; 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.375 lb ai/A PPE = SL w/CR gloves; REI = 12 

hr; PHI = 3 days

Turnips

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.25 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

Wheat

Soil directed; aerial, 

groundboom; 

chemigation; dry bulk 

fertilizer

Liquid and DF 0.19 lb ai/A

PPE = SL w/CR gloves; REI = 12 

hr; PHI = NA (preemergence 

only)

* Use proposed under 1F7838, but not approved due to deficiencies in the residue chemistry database (a ruminant 

feeding study and additional clover residue data).

1

 DF = dry-flowable; G = granular; RTU = ready-to-use.

2

 SLN= special local need.

Table 3.3.2. 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 102

Soybean Anytime

Sugar Beets 36

Sugarcane Anytime

Sunflowers Anytime

Sweet Potatoes 12

Triticale 4

Tobacco Anytime

Turf Anytime
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 17 of 57

Table 3.3.2. Plantback Intervals for Use of Sulfentrazone.

Rotational Crop1Plantback Interval (months)

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.

3.4 Anticipated Exposure Pathways

Based on the registered and proposed sulfentrazone application scenarios, dietary exposure is an 

anticipated exposure pathway as residues of sulfentrazone may be found in/on crops, livestock 

commodities, and drinking water. There are residential uses of sulfentrazone and potential for 

spray drift, so there is exposure in residential and non-occupational settings. In an occupational 

setting, applicators may be exposed while handling the pesticide prior to application, as well as 

during application. There is also potential for post-application exposure for workers re-entering 

treated sites. This risk assessment considers all of the aforementioned exposure pathways based 

on the existing and proposed uses of sulfentrazone.

3.5 Consideration of Environmental Justice

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://epa.gov/compliance/ej/resources/policy/exec_order_12898.pdf). As a part of every

pesticide risk assessment, the Office of Pesticide Programs (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 U.S. Department of Agriculture’s National Health and Nutrition Examination Survey, 

What We Eat in America, (NHANES/WWEIA) 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 and ethnic group. 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 toddlers, youths, 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.

4.0 Hazard Characterization and Dose-Response Assessment

Sulfentrazone belongs to a class of herbicides that inhibit PPO in target photosynthetic 

organisms, ultimately resulting in disruption of chlorophyll biosynthesis. In mammals, PPO is 

also an important enzyme in heme biosynthesis and its inhibition can lead to toxic effects 

associated with disruption of heme utilization (e.g., red blood cells). Some of the toxicities 

reported for sulfentrazone in mammals are consistent with a PPO inhibition.
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 18 of 57

4.1 Toxicology Studies Available for Analysis

The toxicological database for sulfentrazone is complete for risk assessment purposes. A 28-day

rat immunotoxicity study has been submitted to the Agency and reviewed. In addition, HED’s 

Hazard Science and Policy Council (HASPOC) met on February 16, 2012 (TXR# 0050684) to 

evaluate the need for a repeated exposure inhalation toxicity study with sulfentrazone and 

concluded, based on a weight-of-evidence (WOE) approach, that a subchronic rat inhalation 

study was required. Since then, the subchronic inhalation study has been submitted and 

reviewed by the Agency. The results from both studies are included in this hazard assessment. 

4.2 Absorption, Distribution, Metabolism, & Excretion (ADME)

In radiolabel-based studies in the rat, sulfentrazone was well absorbed via the oral route of 

administration as indicated by the excretion of nearly all radioactivity (~84-104%) in the urine 

by 72 hours post-dosing. There was no indication of accumulation; only the carcass, liver, and 

bone showed detectable levels of radioactivity (<0.5% of the administered) at 72 hours postdosing. The pooled urinary radioactivity consisted almost entirely of HMS; the parent chemical 

was not detected in urine and found only at very low levels in feces. There were no apparent 

sex-dependent differences in ADME behavior noted.

4.2.1 Dermal Absorption

There are no dermal absorption studies available for sulfentrazone; however, there is a rat 28-day

dermal toxicity study and a dermal route-specific rat prenatal developmental toxicity study that 

can be used to assess risk via the dermal route of exposure.

4.3 Toxicological Effects

Subchronic and chronic toxicity studies in rats, mice, and dogs identified the hematopoietic 

system as the target of sulfentrazone. Sulfentrazone inhibits the enzyme PPO in target plants and 

the results of subchronic and chronic toxicity studies in mammalian systems are consistent with 

PPO inhibition. Disruption of heme biosynthesis was indicated by signs of anemia [decreases in 

hematocrit (Hct), hemoglobin (HGB), and mean corpuscular volume (MCV)] in mice, rats, and 

dogs at comparable dose levels from short- through long-term exposure without a significant 

increase in severity. 

Sulfentrazone caused developmental effects when administered via the oral (rats and rabbits) and 

dermal (rat) routes of exposure. Developmental effects in rats and rabbits consisted of 

reductions in the number of implantations (rats only), increases in early resorptions (rats and 

rabbits), and reduction in live fetuses per litter (rats and rabbits). Surviving rat fetuses exhibited 

reduced/delayed skeletal ossifications, and decreased fetal body weights. Developmental effects 

in rats were seen in the absence of maternal toxicity. In contrast with the rat studies, 

developmental effects in rabbits were observed at a maternally toxic dose, where clinical signs of 

toxicity included hematuria (red blood cells in urine), abortions, and decreased body-weight 

gains. In the two-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 body-weight deficits, along with reduced pup 

and litter postnatal survival, were also observed. All of the offspring effects were reported in the 

presence of mild maternal toxicity (decreased body weight and body-weight gain, particularly in 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 19 of 57

F1 females).

A published, non-guideline developmental toxicity study in the rat [DeCastro VL, Destefani CR, 

Diniz C, Poli P., 2007. Evaluation of neurodevelopmental effects on rats exposed prenatally to 

sulfentrazone. Neurotoxicology 28(6):1249-59] did not conclusively demonstrate developmental 

neurotoxicity and contains several shortcomings that limit its use for regulatory purposes 

including the lack of a NOAEL. The reported effects involving measures of physical and reflex 

development are likely secondary effects reflective of the poor general state of the offspring as 

reported in the rat two-generation reproductive toxicity study at similar dose levels but with a 

well-defined NOAEL [more information on the review of this study can be found in a previous

risk assessment (K. Lowe et al., 22-DEC-2010; D364882) and Memo, C. Rodriguez, 19-DEC2011, D389975]. 

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 adult non-pregnant rabbits. In a dermal developmental study in 

rats, there was an increased quantitative fetal susceptibility. While no maternal effects were 

observed up to the highest dose tested (250 mg/kg/day), fetal effects were observed at this dose, 

and consisted of decreased body weights, increased incidences of fetal variations; hypoplastic or 

wavy ribs, incompletely ossified lumbar vertebral arches, incompletely ossified ischia or pubis,

and a reduced number of thoracic vertebral and rib ossification sites.

In the 26-day inhalation toxicity study, effects that were considered treatment related and adverse 

occurred only at the highest concentration tested (1.71 mg/L). Systemic effects at this 

concentration consisted of significant reductions in red blood cell (RBC) parameters including 

RBC count, HGB concentrations, Hct, MCV, mean corpuscular HGB (MCH), and/or 

reticulocytes in both sexes. Portal-of-entry effects consisted of an increased incidence of 

minimal nasal respiratory epithelial hyperplasia in both sexes as well as minimal laryngeal 

epithelial attenuation in all test material exposure groups. The effects on hematological 

parameters were reversible after 28 days of recovery, while the nasal injury persisted. 

In an ACN study in rats, effects consisted of 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 at a high dose level (750 mg/kg bw). 

Complete recovery was observed by day 14, and there was no evidence of neuropathology. In a 

rat subchronic neurotoxicity (SCN) study, clinical signs of toxicity, increased motor activity, 

and/or decreased body weights, body-weight gain, and food consumption were also observed 

with no evidence of neuropathology. 

In the 28-day rat immunotoxicity study, there were no effects on the immune system and 

systemic effects consisted of reduced body weight, and increased absolute and relative spleen 

weights at the highest dose tested.

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

formation due to treatment with sulfentrazone, and the Cancer Assessment Review Committee 

(CARC) 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. There is no evidence that 

sulfentrazone is mutagenic in bacterial cells or clastogenic in male or female mice in vivo.
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 20 of 57

Based on the results of acute toxicity studies in the rat, sulfentrazone was classified as Toxicity

Category III (Toxicity Category IV being the lowest category) for acute toxicity via the oral, 

dermal, and inhalation routes of exposure. It was a mild eye irritant (Toxicity Category III), but 

not a dermal irritant or sensitizer. 

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)

The RAB1 risk assessment team recommends that the FQPA SF be reduced to 1X for all 

exposure scenarios. The toxicity database is complete and dietary and residential exposure 

analyses are unlikely to underestimate exposure. Although effects were seen in neurotoxicity

studies and there is evidence of susceptibility to offspring in developmental studies, the effects 

are well-characterized with clearly established NOAEL/lowest-observed adverse-effect level 

(LOAEL) values and selected endpoints are protective for the observed effects.

4.4.1 Completeness of the Toxicology Database

The existing toxicology database for sulfentrazone is adequate for FQPA evaluation. 

Developmental toxicity studies in rats and rabbits, a two-generation reproduction study in rats, 

and neurotoxicity studies in rats are available for FQPA consideration.

4.4.2 Evidence of Neurotoxicity

In the ACN and SCN studies, observed effects included changes in motor activity and FOB 

parameters, clinical signs, and body weight decrements. There is low concern for neurotoxicity

since: 1) effects were seen at relatively high doses; 2) effects occurred in the absence of 

neuropathology; 3) there is no evidence of neurotoxicity in other available studies in the toxicity

database; 4) effects are well-characterized with clearly established NOAEL/LOAEL values; and 

5) the selected PODs are protective of these effects.

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

There was evidence for increased (quantitative) susceptibility following oral and dermal 

exposures in the developmental toxicity studies in rats. Although developmental toxicity was 

observed at lower doses than maternal toxicity in both studies in the rat, the concern is low based 

on the following considerations: 1) the toxicology database for assessing pre- and postnatal

susceptibility is complete; 2) there are clear NOAELs and LOAELs for the developmental 

effects observed via both the oral and dermal routes; 3) the PODs used for assessing dietary and 

dermal exposure risks are based on developmental and/or offspring toxicity; 4) the portal-ofentry effects seen in the 26-day inhalation study are protective of the developmental toxicity; and 

5) there are no residual uncertainties for pre-and/or postnatal toxicity. 

4.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the exposure database. The dietary and residential 

exposure analyses are conservative in nature. The dietary exposure assessment used tolerancelevel residues and assumed 100% CT. The residential exposure assessment uses the 2012 

Residential SOPs and is considered health-protective. The residential assessment includes an 

FQPA SF of 10X for inhalation exposures to account for the uncertainty associated with the lack 

of an appropriate inhalation toxicity study. 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 21 of 57

4.5 Toxicity Endpoints and Point of Departure Selections

4.5.1 Dose-Response Assessment

Table 4.5.4 summarizes the toxicological doses and endpoints selected for residential 

dietary/non-dietary and occupational risk assessment. The rationale for any changes is provided 

below and the updated endpoints are included in Table 4.5.4. 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 years old): This acute dietary endpoint is based on 

increased gestation duration, reduced pre-/postnatal litter and pup survival, reduced litter size, 

increased number of stillborn pups, reduced postnatal survival (pups and litter), and pup bodyweight deficits throughout lactation in both generations of offspring observed in the twogeneration reproductive toxicity study in rats. The developmental effects were reported in the 

presence of mild maternal toxicity (decreased body weight and body-weight gain, particularly in 

F1 females). It has been HED’s practice to consider various forms of developmental toxicity, 

such as the 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 effect 

and are more appropriate for a repeated-exposure scenario. Furthermore, EPA has not 

traditionally considered delays in ossification (and related fetal body-weight deficits) to be 

single-dose effects. The conventional 100-fold uncertainty factor (10X inter-, and 10X 

intraspecies) was applied to the NOAEL (14 mg/kg bw/day). The FQPA SF was reduced to 1X 

(see Section 4.4). Thus, the acute reference dose (aRfD) and aPAD are equivalent at 0.14 mg/kg 

bw/day.

Acute Dietary Endpoint (General population, including infants and children): This acute 

endpoint is based upon increased incidence of clinical signs, FOB findings, and decreased motor 

activity at the LOAEL of 750 mg/kg bw seen following a single oral administration in the ACN 

study. The aRfD and aPAD are equivalent at 2.5 mg/kg bw/day based on the NOAEL of 250 

mg/kg/day from the ACN study and a 100-fold uncertainty factor (10X interspecies, 10X 

intraspecies, 1X FQPA).

Chronic Dietary Endpoint (All populations): The chronic dietary endpoint is based on increased 

gestation duration, reduced pre-/postnatal litter and pup survival, and pup body-weight deficits 

throughout lactation in both generations of offspring observed at the LOAEL of 33 and 40 

mg/kg/day in males and females, respectively in the rat two-generation reproductive toxicity

study. This LOAEL is based on developmental toxicity, the most sensitive endpoint, and is 

protective of developmental and chronic effects seen in other studies. The chronic reference 

dose (cRfD) and cPAD are equivalent at 0.14 mg/kg bw/day based on the NOAEL of 14 

mg/kg/day in the two-generation reproductive toxicity study and a 100-fold uncertainty factor 

(10X interspecies, 10X intraspecies, 1X FQPA).

Incidental Oral Endpoint (Short- and intermediate-term): This endpoint is based on offspring 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 22 of 57

toxicity observed in the rat two-generation reproductive toxicity study in the form of reduced 

pre-/postnatal litter and pup survival, and pup body-weight deficits throughout lactation in both 

generations of offspring observed at the LOAEL of 33 and 40 mg/kg/day in males and females, 

respectively (lowest NOAEL = 14 mg/kg/day for males). The effects seen in the offspring are 

appropriate for the population (infants and children) and durations (short- and intermediate-term) 

of concern. The LOC for incidental oral risk estimates is for MOEs less than 100, which 

includes the 10X inter- and 10X-intraspecies factors. The FQPA SF was reduced to 1X (see 

Section 4.4).

Dermal Endpoints (Short- and intermediate-term): The dermal developmental toxicity study in 

rats was selected to assess dermal exposures (NOAEL =100 mg/kg/day). The LOAEL is based 

on developmental toxicity. This endpoint is appropriate since the developmental effects were 

seen after repeated exposure via the dermal route. The LOC for occupational and nonoccupational dermal risk estimates is for MOEs less than 100, which includes the 10X inter- and 

10X intraspecies factors. The FQPA SF was reduced to 1X (see Section 4.4).

Inhalation Endpoints (Short- and intermediate-term): The short- and intermediate-term 

inhalation endpoints were derived from the route specific 26-day inhalation study in rats where 

the NOAEL is 0.256 mg/L. The LOAEL is 1.71 mg/L for both sexes based on significant 

reductions in RBC parameters, including RBC count, HGB, Hct, MCV, MCH, and/or 

reticulocytes in male and female rats following 26 days of inhalation exposure to the test 

material. Portal-of-entry effects at this dose were also observed and manifested as an increased 

incidence of minimal nasal respiratory epithelial hyperplasia in both sexes as well as minimal 

laryngeal epithelial attenuation in all test material exposure groups. As described below, humanequivalent concentrations and doses (HECs and HEDs) were calculated based this subchronic 

inhalation study. This inhalation study is protective for the systemic effects (including 

developmental effects seen in the oral studies) for the following reasons: 1) the dose spread in 

the inhalation study between the NOAEL and LOAEL is large (40 to 600 mg/kg/day) and the 

effects in the nasal passage likely start a lower dose than the LOAEL; 2) the reference 

concentration (RfC) methodology calculations include a 15-fold lower regional deposited dose 

ratio for portal-of-entry effects (0.213) compared to systemic effects (3.129); and 3) the 

estimated inhalation HEDs are lower or equivalent (depending on the exposure scenario being 

assessed) than the oral NOAEL from the developmental study.

HECs derived from this study were based upon the increased incidence of minimal nasal 

respiratory epithelial hyperplasia in male and female rats. The resulting HECs are 0.04 and 0.05

mg/L for occupational handler and residential handler. Portal-of-entry effects were used to 

generate HECs and are protective for any systemic effects (portal-of-entry HEC = 0.04 mg/L vs. 

systemic RBC HEC = 0.60 mg/L for occupational, and portal-of-entry HEC = 0.05 mg/L vs. 

systemic RBC HEC = 0.801 mg/L). HEDs were subsequently calculated for occupational 

handler exposure scenarios based upon ventilation rates of 8.3, 16.7, and 29 L/min (2.317, 4.661,

and 8.094 mg/kg/day) and residential-handler exposure scenarios based upon a ventilation rate of 

16.7 L/min (1.55 mg/kg/day). For details regarding the calculation of the HECs and HEDs, see 

Appendix B. These HEDs are protective of the systemic effects observed through the inhalation 

route. This study is thus appropriate for the route and duration of exposure, and as described 

above in Section 4.3, use of this inhalation study is protective of any potential developmental 

effects seen in the oral rat developmental study.

The LOC is 30 which includes interspecies (3X) and intraspecies (10X) uncertainty factors. The 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 23 of 57

interspecies factor was reduced from 10X to 3X due to the HEC calculation accounting for 

pharmacokinetic (not pharmacodynamic) interspecies differences.

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

The Agency must consider risks from individual routes of exposure (oral, dermal, and inhalation) 

and perform combined exposure and risk assessments if a common toxicity endpoint is 

established across different routes of exposure. Since developmental effects (fetal body-weight 

deficits and skeletal effects) were observed in the studies used to select the PODs for the dermal 

and oral exposure routes, these routes should be combined. 

4.5.3 Cancer Classification and Risk Assessment Recommendation

The CARC has classified sulfentrazone as “not likely to be carcinogenic” to humans (TXR #: 

011910) in accordance with EPA proposed Guidelines for Carcinogenic Risk Assessment (April 

10, 1996).

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human-Health 

Risk Assessment

Table 4.5.4.1. Summary of Toxicological Doses and Endpoints for Sulfentrazone for Use in Residential and 

Dietary Human-Health Risk Assessment.

Exposure Scenario POD Uncertainty/

FQPA SFs

RfD, PAD, LOC 

for Risk 

Assessment

Study and 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

Two-generation 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

ACN 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 = 14 

mg/kg/day 

UFA = 10X

UFH = 10X

FQPA SF = 

1X

cRfD = cPAD =

0.14 mg/kg/day

Two-generation 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.

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

Two-Generation Reproductive 

Toxicity Study - Rat

Offspring LOAEL = 33 mg/kg/day 

based on decreased pup body weights 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 24 of 57

Table 4.5.4.1. Summary of Toxicological Doses and Endpoints for Sulfentrazone for Use in Residential and 

Dietary Human-Health Risk Assessment.

Exposure Scenario POD Uncertainty/

FQPA SFs

RfD, PAD, LOC 

for Risk 

Assessment

Study and Toxicological Effects

and reduced postnatal survival in both 

generations.

Short- (1-30 days), 

Intermediate- (1-6 

months), and 

Long-Term (>6 

months) Dermal

NOAEL =

100 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Residential LOC 

for MOE = 100

Dermal Developmental Study - Rat

LOAEL = 250 mg/kg/day based on 

decreased fetal body weight; increased 

incidences of fetal skeletal variations: 

hypoplastic or wavy ribs, 

incompletely ossified lumbar vertebral 

arches, and incompletely ossified 

ischia or pubes; and reduced number 

of thoracic vertebral and rib 

ossification sites.

Short- (1-30 days), 

Intermediate- (1-6 

months), and 

Long-Term (>6 

months) Inhalation

Portal-of-entry

NOAEL = 

0.256 mg/L, 

HEC = 0.054 

mg/L, HED = 

1.55 mg/kg/day

UFA = 3X

UFH = 10X

FQPA SF = 

1X

Residential LOC 

for MOE = 30

Portal-of-entry LOAEL = 1.71 mg/L 

based on an increased incidence of 

minimal nasal respiratory epithelial 

hyperplasia in male and female rats. 

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.

Table 4.5.4.2. Summary of Toxicological Doses and Endpoints for Sulfentrazone for Use in Occupational 

Human-Health Risk Assessment.

Exposure Scenario POD Uncertainty/

FQPA SFs

RfD, PAD, 

LOC for 

Risk 

Assessment

Study and Toxicological Effects

Short- (1-30 days), 

Intermediate- (1-6 

months), and LongTerm (>6 months) 

Dermal

NOAEL =

100 mg/kg/day

UFA = 10X

UFH = 10X

Occupational 

LOC for 

MOE = 100

Dermal Developmental Study - Rat

LOAEL = 250 mg/kg/day based on 

decreased fetal body weight; increased 

incidences of fetal skeletal 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

Portal-of-entry 

NOAEL = 

0.256 mg/L

HEC = 0.041 

mg/L

HED (8.3 

L/min) = 2.317 

mg/kg/day

HED (16.7 

L/min) = 4.661 

UFA = 3X

UFH = 10X

Occupational 

LOC for 

MOE = 30

Portal-of-entry LOAEL = 1.71 mg/L 

based on an increased incidence of 

minimal nasal respiratory epithelial 

hyperplasia in male and female rats. 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 25 of 57

Table 4.5.4.2. Summary of Toxicological Doses and Endpoints for Sulfentrazone for Use in Occupational 

Human-Health Risk Assessment.

Exposure Scenario POD Uncertainty/

FQPA SFs

RfD, PAD, 

LOC for 

Risk 

Assessment

Study and Toxicological Effects

mg/kg/day

HED (29 

L/min) = 8.094 

mg/kg/day

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.

4.6 Endocrine Disruptor Screening Program

As required by Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and Federal Food, 

Drug, and Cosmetic Act (FFDCA), EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic, and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its Registration Review decision for sulfentrazone, EPA reviewed 

these data and selected the most sensitive endpoints for relevant risk assessment scenarios from 

the existing hazard database. However, as required by FFDCA section 408(p), sulfentrazone is 

subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the 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. Under FFDCA 

section 408(p), the Agency must screen all pesticide chemicals. 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. A second list of chemicals 

identified for EDSP screening was published on June 14, 20132and includes some pesticides 

 

2

See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 26 of 57

scheduled for registration review and chemicals found in water. Neither of these lists should be 

construed as a list of known or likely endocrine disruptors. For further information on the status 

of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines 

and the Tier 1 screening battery, please visit our website.3

5.0 Dietary Exposure and Risk Assessment

D415626, G. Kramer, 05-JUN-2014 (residue chemistry summary for the current action)

D417172, G. Kramer, 05-JUN-2014 (dietary exposure analysis for the current action)

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant and Animal Metabolism Studies

The nature of the residue in plants is adequately understood. Data concerning the 

metabolism of sulfentrazone following preemergent applications in soybeans and confined 

rotational crops were submitted in conjunction with the soybean petition (PP#4F04407). 

The HED Metabolism Committee 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 (G. Kramer, 14-

JUN-1996; D226434). 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 (G. 

Kramer, 13-MAR-1996; D220548). Data concerning the metabolism of sulfentrazone 

following postemergent applications in corn, soybean, and radish were submitted in 

conjunction with recent petitions (D389972, 5/9/12, G. Kramer). The metabolism of 

sulfentrazone following postemergent application was similar to that seen in rotational crops 

and following preemergent application to soybean; no additional major metabolites were 

identified. HED concludes metabolism data are now available to support postemergence 

applications and that sulfentrazone and its metabolites HMS and DMS (free and conjugated) 

are the residues of concern in all crops except soybean seed, where the residues of concern 

are sulfentrazone and the metabolite HMS.

The nature of the residue in livestock is adequately understood based on acceptable ruminant 

and poultry metabolism studies. 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. 

5.1.2 Summary of Environmental Degradation

Sulfentrazone is expected to be persistent under most environmental conditions. Sulfentrazone 

half-lives in aerobic soil metabolism, anaerobic aquatic metabolism, and terrestrial field dissipation 

studies are one year or longer (1.5 years, 9 years, and 1 to 2 years, respectively). Sulfentrazone is 

stable towards abiotic hydrolysis. Direct photolysis in water appears to be the only transformation 

pathway with observed half-lives of 12 hours at pH 5 and 1 hour at pHs 7 and 9. Many of the 

photolytic products are formed by cleavage of the C to N bond between the phenyl and triazolo 

 

3

See http://www.epa.gov/endo/.
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 27 of 57

rings. Although methyl triazole was the major degradate detected in the aqueous photolysis study, 

the fate of this degradate in the natural environment is unknown because the field dissipation and 

the groundwater monitoring studies did not monitor this degradate. However, photolytic 

breakdown would be more significant in shallow waters of low turbidity than in deep waters of high 

turbidity. The major transformation product observed in soils is the carboxylic acid of 

sulfentrazone (3-carboxylic acid sulfentrazone). This degradate, together with parent sulfentrazone, 

has been detected in groundwater so far in prospective ground-water monitoring studies. In a 

variety of soils ranging in texture from sand to silty clay loam, sulfentrazone is very mobile (Kd, 0.2 

to 0.8; average Koc 43). The pKa of sulfentrazone is 6.5 and, therefore, sulfentrazone would be 

more mobile in neutral to alkaline soils than in acidic soils. The pKa of the carboxylic acid of 

sulfentrazone is not known, but it may be comparable to that of parent sulfentrazone and exhibit a 

similar behavior as the parent in neutral-alkaline soils. The HED Metabolism Assessment Review 

Committee (MARC) concluded that parent and 3-carboxylic acid sulfentrazone are the residues of 

concern for the drinking-water assessment (Memo, G. Kramer et al., 10-APR-2003; D288713). 

HED continues to consider the given metabolites and degradates to be the residues of concern for 

risk assessment. 

5.1.3 Comparison of Metabolic Pathways

In plants, sulfentrazone is metabolized via four different pathways: (1) Oxidation of the 3-methyl 

group to form 3-hydroxymethyl sulfentrazone or HMS, followed by further oxidation to form 

sulfentrazone carboxylic acid which is decarboxylated to 3-desmethyl sulfentrazone or 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 metabolism of sulfentrazone in animals (livestock and rats) 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 carboxylic acid was also the major transformation product observed in soils.

5.1.4 Residues of Concern Summary and Rationale

The residues of concern in primary crops, rotational crops, livestock, and drinking water, as 

identified by the MARC, are shown in Table 5.1.4 below.

Table 5.1.4. Residues of Concern in Crops, Livestock, and Drinking Water.

Matrix Tolerance Expression Residues for Risk Assessment

Primary Crops, except soybean 

seed

sulfentrazone, HMS, DMS

(free and conjugated)

sulfentrazone, HMS, DMS 

(free and conjugated)

Soybean, seed sulfentrazone, HMS sulfentrazone, HMS

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

5.2 Food Residue Profile

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, 

permanent tolerances are established under 40 CFR §180.498(a)(2) for the combined residues of 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 28 of 57

sulfentrazone and its metabolites HMS and DMS in/on several food commodities; these 

established tolerances range from 0.15 ppm (various plant commodities) to 0.60 ppm (turnip tops). 

Tolerances for the combined residues of sulfentrazone and its metabolites HMS and DMS have 

been established under 40 CFR §180.498(c) in connection with regional registrations; these 

include tolerances for residues in/on succulent lima bean, succulent cowpea, and wheat grain at 

0.15 ppm. 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. Pending uses are for the nongrass animal 

feeds crop group 18 (PP#1F7838) and apples (PP#3E8202). Additional residue data and a 

ruminant feeding study are required for proposed use on nongrass animal feeds (Memo, G. 

Kramer, D389972, 09-MAY-2012).

The submitted field trial residue data for all registered crops are adequate. The recently submitted 

field trial residue data apple are also adequate. The field trial data reflect the proposed use 

patterns; an adequate number of trials were conducted in the appropriate geographic regions; and 

samples were analyzed for the residue of concern using validated data-collection methods. The 

storage intervals were also validated. However, an additional six clover trials are required to 

support the proposed use on nongrass animal feeds (Memo, G. Kramer, D389972, 09-MAY-2012).

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. However, a ruminant feeding study is required to support the 

proposed use on nongrass animal feeds crop group 18 (Memo, G. Kramer, D389972, 09-MAY2012). 

Rotational crop studies for corn, rice, sorghum, and wheat were 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. The labeled rotational 

crop restrictions (Table 3.3.2) are adequate for use rates up to 0.375 lb ai/A.

5.3 Drinking Water Residue Profile

Drinking water residues provided by EFED (Memo, M. Barrett, 21-MAY-2014; D415627) were 

incorporated directly into the acute and chronic dietary analyses as “water, direct, all sources” 

and “water, indirect, all sources.” The estimated drinking water concentrations (EDWCs) were 

Tier 1 estimates for ground water using the Pesticide Root Zone Model-Ground Water (PRZMGW) model version 1.07 (Screening Concentration In Ground Water) and surface water using 

the Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS) model. 

The proposed use on apples carries the maximum single and annual application rates for all 

currently registered uses (0.375 lb ai/ A). Previous estimates of sulfentrazone residues in 

drinking water were done separately for parent and the 3-carboxylic acid sulfentrazone 

degradate. Sulfentrazone and 3-carboxylic acid sulfentrazone have a potential to reach both 

surface and ground waters that may be used as drinking water sources. This revised assessment 

has now taken a total toxic residues (TTR) approach to assessing exposure, instead of providing 

values for each compound individually.
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 29 of 57

For surface water, the highest acute (peak) sulfentrazone value is 37.3 ppb and the 10-year 

average value is 5.3 ppb. For ground water, the highest daily value (peak) sulfentrazone value is 

134 ppb and the post-breakthrough-average value is 98 ppb. EDWCs of 0.134 ppm and 0.098 

ppm were used in the acute and chronic analyses, respectively.

Table 5.3. Estimated Tier 1 Concentrations of Sulfentrazone and 3-Carboxylic Acid Sulfentrazone in 

Drinking Water Due to the Use of Sulfentrazone.

Scenario

Surface Water (ug/L) Groundwater (ug/L)

Acute Chronic Acute Chronic

FL Sugarcane 37.3 3.2 - -

LA Corn 31.3 5.3 - -

Delmarva Sweet Corn - - 134 98

5.4 Dietary (Food + Drinking Water) Risk Assessment

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments 

were conducted using DEEM-FCID, ver. 3.16 which incorporates consumption data from the 

USDA NHANES/WWEIA; 2003-2008. The acute and chronic analyses assumed tolerance-level 

residues, 100% CT, DEEM (ver. 7.81) default processing factors, and modeled drinking water 

estimates. The highest acute exposure estimate was for the population subgroup all infants <1 

year old, which utilized 1.1% of the aPAD for sulfentrazone. Females 13-49 years old have a 

lower aPAD than the general population. As a result, even though the exposure estimate for 

females 13-49 years old was lower than the estimate for infants <1 year old, females 13-49 years 

old is the population subgroup with the highest risk estimate (≤7% aPAD). The highest chronic 

exposure estimate was for the population subgroup children 1-2 years old, which utilized 7.1% of 

the cPAD for sulfentrazone. 

Table 5.4.1. Summary of Acute and Chronic Dietary (Food and Drinking Water) Exposure and Risk 

for Sulfentrazone.1

Population Subgroup

95th Percentile cPAD 

(mg/kg/day)

Exposure 

(mg/kg/day) aPAD %cPAD

(mg/kg/day)

Exposure 

(mg/kg/day) %aPAD

General U.S. Population

2.5

0.011114 <1.0

0.14

0.003973 2.8

All Infants (<1 year old) 0.026754 1.1 0.008577 6.1

Children 1-2 years old 0.022692 <1.0 0.009881 7.1

Children 3-5 years old 0.017984 <1.0 0.007889 5.6

Children 6-12 years old 0.011833 <1.0 0.004817 3.4

Youth 13-19 years old 0.008607 <1.0 0.003225 2.3

Adults 20-49 years old 0.009187 <1.0 0.003498 2.5

Adults 50-99 years old 0.008301 <1.0 0.003314 2.4

Females 13-49 years old 0.14 0.009363 6.7 0.003450 2.5

1 The populations with the greatest risk and exposure estimates are bolded.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

D417171, K. Lowe, 05-JUN-2014

The proposed use on apples is not expected to result in residential exposure. The previous 

exposure assessment for sulfentrazone assessed the registered residential uses on turfgrass using 

the 2012 Residential SOPs (Memo, K. Lowe, D389974, 17-MAY-2012) and covers most of the 

scenarios necessary for Registration Review. Residential handler and post-application scenarios 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 30 of 57

were assessed at a maximum application rate of 0.375 lb ai/A for liquid, granular, and dry

flowable formulations (identified in the 2009 scoping document for sulfentrazone; Memo, K. 

Lowe et al., D369064, 09-SEP-2009). There were no residential risk estimates of concern 

identified.

Updated risk estimate tables have been included in this memo for residential handlers since the 

inhalation POD and LOC for sulfentrazone has been changed since the previous assessment. In 

addition, updated risk estimates have been included for the post-application episodic granular 

ingestion scenario based on a revised maximum percent active ingredient for granular 

formulations identified during the label review of registered sulfentrazone labels. 

6.1 Residential Handler Exposure/Risk Estimates

Table 6.1.1 provides a summary of the residential handler exposures and risk estimates for 

sulfentrazone. All dermal and inhalation exposure risk estimates for residential handlers are not 

of concern (i.e., MOEs ≥ 100 for dermal and MOEs ≥ 30 for inhalation) at baseline for all 

scenarios. 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 31 of 57

Table 6.1.1. Residential Handler Non-cancer Exposure and Risk Estimates for Sulfentrazone.

Exposure Scenario Level of 

Concern

Dermal Unit 

Exposure 

(mg/lb ai)

Inhalation 

Unit Exposure 

(mg/lb ai)

Maximum 

Application 

Rate1

Area Treated or 

Amount Handled 

Daily2

Dermal

(LOC = 100)

Inhalation

(LOC = 100)

Dose 

(mg/kg/day)3 MOE4 Dose (mg/kg/day)5 MOE6

Loader/Applicator for Granules

Push-type spreaders

100

0.81 0.0026 0.375 lb ai/A 0.5 A 0.0022 45,000 0.0000061 250,000

Belly grinders 360 0.039

0.0000086 lb 

ai/ft2

1200 ft20.054 1,900 0.000005 310,000

Spoon 6.2 0.087

100 ft2

0.000077 1,300,000 0.00000094 1,700,000

Cup 0.11 0.013 0.0000014 73,000,000 0.00000014 11,000,000

Hand dispersal 160 0.38 0.002 50,000 0.0000041 380,000

Shaker can 0.11 0.013 0.0000014 73,000,000 0.00000014 11,000,000

Mixer/Loader/Applicator for Liquids

Manually-pressurized 

handwand

100

63 0.018 0.019 lb 

ai/gallon 5 gallons 0.087 1,200 0.000021 73,000

Hose-end sprayer 13.4 0.022 0.375 lb ai/A 0.5 A 0.036 2,700 0.000052 30,000

Backpack 130 0.14 0.019 lb 

ai/gallon 5 gallons 0.18 560 0.00017 9,300

Sprinkler can 13.4 0.022 0.0000086 lb 

ai/ft2 1000 ft2

0.0017 60,000 0.0000024 660,000

Mixer/Loader/Applicator for Dry Flowables

Manually-pressurized 

handwand

100

69 1.1 0.019 lb 

ai/gallon 5 gallons 0.095 1,100 0.0013 1,200

Hose-end sprayer 13.4 0.022 0.375 lb ai/A 0.5 A 0.036 2,700 0.000052 30,000

Backpack 69 1.1 0.019 lb 

ai/gallon 5 gallons 0.095 1,100 0.0013 1,200

Sprinkler can 13.4 0.022 0.000008 lb 

ai/ft2 1000 ft2

0.0016 64,000 0.0000022 700,000

1 Based on registered labels (see Table 3.3.1).

2 Based on HED’s 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residential-exposure-sop.html).

3 Dermal Dose = Dermal Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A/day or 

gallons/day) ÷ Body Weight (69 kg).

4 Dermal MOE = Dermal NOAEL (100 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

5

Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A/day or 

gallons/day) ÷ Body Weight (80 kg).

6

Inhalation MOE = Inhalation NOAEL (1.55 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 32 of 57

6.2 Residential Post-application Exposure/Risk Estimates

Table 6.2.1 provides a summary of the residential post-application exposures and risk estimates 

for sulfentrazone. All risk estimates for post-application exposure are not of concern (i.e., MOEs 

≥ 100); all MOEs were ≥ 610 for adults and ≥ 360 for children. 

Table 6.2.1. Short-Term Residential Post-application Exposure and Risk Estimates for Sulfentrazone.

Lifestage Post-application Exposure Scenario Dose (mg/kg/day)1 MOEs2 Combined 

MOEs

Liquid formulation

Adult

Turf

Liquid 

formulation

0.375 lb ai/A

Dermal

Physical Activities on Turf 0.16 610

N/A

Mowing 0.0033 30,000

Golfing 0.013 7,800

Child 11 to < 16 

years old Dermal Mowing 0.0033 30,000

Golfing 0.013 7,800

Child 6 to < 11 

years old Dermal Golfing 0.015 6,600

Child 1 to< 2 year 

old

Dermal Physical Activities on Turf 0.28 360 310 Hand to Mouth 0.0057 2,500

Object to Mouth 0.00017 81,000

Short- and Intermediate-term Incidental Soil N/A

Ingestion 1.3 x 10-5

1,100,000

Granular formulation

Adult

Turf

Granular 

formulation

0.375 lb ai/A

Dermal

Physical Activities on 

Turf 0.036 2,800

N/A

Mowing 0.00066 150,000

Golfing 0.0026 39,000

Child 11 to < 16 

years old Dermal Mowing 0.00066 150,000

Golfing 0.0026 39,000

Child 6 to < 11 

years old Dermal Golfing 0.0030 33,000

Child 1 to < 2 

year old

Dermal Physical Activities on 

Turf 0.061 1,600 1,500

Hand to Mouth 0.00057 25,000

Object to Mouth 0.000035 400,000

N/A Short- and Intermediate-term Incidental Soil 

Ingestion 1.3 x 10-5

1,100,000

0.4% ai Episodic Granular Ingestion 0.11 130

1

 Dose (mg/kg/day) equations provided in Appendix B.

2

 MOE = POD (dermal = 100 mg/kg/day and incidental oral = 14 mg/kg/day) ÷ Dose (mg/kg/day). LOC = 100.

6.3 Residential Risk Estimates for Use in Aggregate Assessment

Table 6.3.1 reflects the residential risk estimates that are recommended for use in the aggregate 

assessment for sulfentrazone.

 The recommended residential exposure for use in the adult short-term aggregate 

assessment reflects dermal exposure from applications to turf via backpack sprayer.

 The recommended residential exposure for use in the children 1 < 2 years old short-term 

aggregate assessment reflects dermal and hand-to-mouth exposures from post-application 

exposure to turf applications.
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 33 of 57

Table 6.3.1. Recommendations for the Residential Exposures for the Sulfentrazone Aggregate Assessment.

Lifestage Exposure 

Scenario

Dose (mg/kg/day)1 MOE2

Dermal Inhalation3 Oral Total Dermal Inhalation3 Oral Total

Short-term

Adult

Male

Handler –

MLA liquids 

via 

backpack

0.18 N/A N/A 0.18 560 N/A N/A 560

Child 11 < 

16 years old

Postapplication 

exposure 

from golfing 

(liquid 

formulation) 

0.013 N/A N/A 0.013 7,800 N/A N/A 7,800

Child 6 < 11 

years old

Postapplication 

exposure 

from golfing 

(liquid 

formulation) 

0.015 N/A N/A 0.015 6,600 N/A N/A 6,600

Child 1 < 2 

year old

Postapplication 

exposure 

from 

activities on 

turf (liquid 

formulation) 

0.28 N/A 0.0057 0.28 360 N/A 2,500 310

1

 Dose = the highest dose for each applicable lifestage of all residential scenarios assessed. Total = dermal + incidental oral (where applicable).

2

 MOE = the MOEs associated with the highest residential doses. 

3

 Inhalation risk estimates were not combined with dermal or oral risk estimates in this assessment since the toxicological effects in the inhalation 

toxicological study were portal-of-entry and different from those seen in the dermal and oral toxicological studies.

6.4 Spray Drift

Off-target movement of pesticides can occur via many types of pathways and it is governed by a 

variety of factors. Sprays that are released and do not deposit in the application area end up offtarget and can lead to exposures to those it may directly contact. They can also deposit on 

surfaces where contact with residues can eventually lead to exposures (e.g., children playing on 

lawns where residues have deposited next to treated fields). The potential risk estimates from 

these residues can be calculated using drift modeling coupled with methods employed for 

residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment include 

assessing exposures for children (1 to <2 years old) and adults who have contact with turf where 

residues are assumed to have deposited via spray drift thus resulting in an exposure scenario. 

Aside from the predicted residues available for transfer, the routes of exposure and assessment 

methodology is analogous to how exposures to turf products are considered in risk assessment. 

Several sulfentrazone products have existing labels for use on turf, thus it was considered 

whether the risk assessment for turf may be considered protective of any type of exposure 

resulting from spray drift. If the maximum application rate on crops adjusted by the amount of 

drift expected is less than or equal to existing turf application rates, the existing turf assessment 

is considered protective of spray drift exposure. The proposed maximum single application rate 

of sulfentrazone for several registered agricultural crops is 0.375 lb ai/A. The highest fraction of 

spray drift noted for any application method immediately adjacent to a treated field results in a
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 34 of 57

deposition fraction of 0.264of the application rate. A quantitative spray drift assessment for 

sulfentrazone is not required because the maximum application rate for a crop/target site 

multiplied by the adjustment factor for drift of 0.26 is less than the maximum direct spray

residential turf application rate (0.375 lb ai/A)5for any sulfentrazone products. The turf postapplication MOEs are protective for any potential exposures related to spray drift for 

sulfentrazone and have previously been discussed in Section 5.2. 

6.5 Residential Bystander Post-Application Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for sulfentrazone at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category III) and the low vapor pressure (8 x 10-10 mm Hg). 

However, volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The Agency sought expert advice and input on issues 

related to volatilization of pesticides from its FIFRA Scientific Advisory Panel (SAP) in 

December 2009, and received the SAP’s final report on March 2, 20106. The Agency is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to 

identify the need for and, subsequently, the way to incorporate post-application inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are developed, the 

Agency may revisit the need for a quantitative post-application inhalation exposure assessment 

for sulfentrazone.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure. 

7.1 Acute Aggregate Risk

Acute aggregate risk results from exposure to residues in food and drinking water alone. The 

acute dietary exposure analysis included both food and drinking water. Therefore, acute 

aggregate risk is equivalent to the acute dietary risk, as discussed in Section 5.4, above. All risk 

estimates are not of concern. 

7.2 Short- and Intermediate-Term Aggregate Risk

Short- and intermediate-term aggregate exposure takes into account short- and intermediate-term 

residential exposure plus chronic exposure to food and water (considered to be a background 

exposure level). Sulfentrazone is currently registered for uses that could result in short- and 

intermediate-term residential exposure, and RAB1 has determined that it is appropriate to 

aggregate chronic exposure through food and water with short- and intermediate- term residential 

exposures to sulfentrazone. For short- and intermediate-term exposures, incidental oral and 

 

4 Tier 1 output from the aerial application using fine to medium spray quality based on AgDrift®

output files

5

0.375 lb ai/A x 0.26 ≤ 0.375 lb ai/A

6 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 35 of 57

dermal exposure risk assessments are appropriate to aggregate due to similarities in the toxicity

endpoints observed between the oral and dermal routes. The short- and intermediate-term 

incidental oral and dermal exposures are combined with chronic dietary (food and water) 

exposure for determination of aggregate short- and intermediate-term exposures. HED uses 

chronic dietary exposure when conducting short- and intermediate-term aggregate assessments as

they have determined that these will more accurately reflect exposure from food over the HED 

defined short- and intermediate-term interval than will acute exposure. 

Adults may potentially be exposed to sulfentrazone through dermal, inhalation, and dietary (food 

and drinking water) routes. It was appropriate to aggregate handler dermal exposures with 

dietary (food and water) exposures for the short- and intermediate-term duration. The backpack 

scenario for mixing and loading liquids is the exposure scenario with the greatest risk estimate; 

therefore, the exposure estimates for this scenario are protective of other exposure scenarios. For 

young children, due primarily to their hand-to-mouth activities, short-term oral (non-dietary) 

exposures are expected along with dermal and dietary (food and drinking water) exposures; 

therefore, it was appropriate to aggregate these exposures for the short- and intermediate-term 

duration. Children 1-2 years old represent the population subgroup for children with the greatest 

exposure; therefore, the exposure estimates for children 1-2 years old are protective of other 

children population subgroups. The LOC is 100; therefore MOEs <100 are risk estimates of 

concern. 

Tables 7.2.1 and 7.2.2 summarize the short- and intermediate-term aggregate exposures and risk 

estimates for 1-2 year olds and adults. The aggregate short- and intermediate-term MOEs are 

>100 for adults and children; therefore, aggregate exposures to sulfentrazone are not of concern 

to HED.

Table 7.2.1. Short- and Intermediate-term Aggregate Risk Calculations for Children 1-2 Years Old.

Population LOC

Background Dietary + Incidental Oral Exposures Residential Exposures Aggregate 

MOE (food, 

water, and 

residential)4

Chronic Food and 

Water Exposure 

(mg/kg/day)

Incidental 

Oral Exposure 

(mg/kg/day)1

Oral MOE2

Dermal 

Exposure 

(mg/kg/day)

Dermal 

MOE3

Children 1-

2 years old 100 0.009881 0.0057 900 0.28 360 260

1

Short-term Incidental Oral Exposure = Hand-to-mouth exposure. 

2 Oral MOE = NOAEL (14 mg/kg/day) ÷ (chronic food/water exposure + incidental oral exposure).

3 Dermal MOE = NOAEL (100 mg/kg/day) ÷ (dermal exposure). 

4 Aggregate MOE = 1/[(1/oral MOE) + (1/dermal)].

Table 7.2.2. Short-Term Aggregate Risk Calculations for Adults.

Population

Dietary Exposure1 Dermal Residential Exposure2

Aggregate MOE (food, 

water, and residential) Chronic Food and Water 3

Exposure (mg/kg/day) MOE Dermal Exposure (mg/kg/day) MOE

General 

U.S. 

Population

0.003973 3500 0.18 560 480

1 MOE dietary = [(short- or intermediate-term oral NOAEL = 14 mg/kg/day)/(chronic dietary exposure)]. 

2 MOE dermal = [(short- or intermediate-term dermal NOAEL = 100 mg/kg/day)/(high-end dermal residential exposure)]. 

3 Aggregate MOE = 1/[(1/dietary MOE) + (1/dermal MOE) + (1/inhalation MOE)].

7.3 Chronic Aggregate Risk

The chronic aggregate risk assessment results from long-term exposure to residues in food and 

drinking water, as there are no residential scenarios that result in long-term exposure. The 

chronic dietary exposure analysis included both food and drinking water and, therefore, the 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 36 of 57

chronic aggregate risk assessment is equivalent to the chronic dietary risk assessment discussed 

in Section 5.4, above. All risk estimates are not of concern. 

7.4 Cancer Aggregate Risk

An aggregate cancer risk assessment was not performed because sulfentrazone is not considered 

to be a carcinogen. 

8.0 Cumulative Exposure/Risk Characterization

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 substances and sulfentrazone does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that sulfentrazone has 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/.

9.0 Occupational Exposure/Risk Characterization

D417171, K. Lowe, 05-JUN-2014

9.1 Handler Risk Assessment

The occupational handler exposure and risk estimates indicate that the short- and intermediateterm dermal and inhalation MOEs are not of concern to HED (i.e., MOEs >100 for dermal and 

MOEs >30 for inhalation), as long as gloves are worn for the highest application rate for 

mixing/loading liquids and dry flowables for aerial application to high-acreage crops.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for 

exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the 

engineering control (enclosed cockpits) and baseline attire (long-sleeve shirt, long pants, shoes, 

and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, 

pilots are not required to wear protective gloves for the duration of the application. With this 

level of protection, there are no risk estimates of concern for applicators.

The Agency matches quantitative occupational exposure assessment with appropriate 

characterization of exposure potential. While HED presents quantitative risk estimates for 

human flaggers where appropriate, agricultural aviation has changed dramatically over the past 

two decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of 

their membership, the use of Global Positioning System (GPS) for swath guidance in agricultural 

aviation has grown steadily from the mid-1990s. Over the same time period, the use of human 

flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 1990s to 

only 1% in the most recent (2012) NAAA survey. The Agency will continue to monitor all 

available information sources to best assess and characterize the exposure potential for human 

flaggers in agricultural aerial applications.
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 37 of 57

Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Sulfentrazone. 

Exposure Scenario Crop or Target

Dermal Unit 

Exposure 

(μg/lb ai)1

Inhalation Unit 

Exposure 

(μg/lb ai)1 Maximum 

Application 

Rate (lb 

ai/A)2

Area 

Treated 

(acres)3

Dermal

(LOC = 100)

Inh

(LO

Mitigation 

Level = 

baseline unless 

indicated 

otherwise

Mitigation Level 

= baseline 

unless indicated 

otherwise

Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day

Mixer/Loader

Aerial application of dry 

flowable

Nursery (ornamentals, 

vegetables, trees, 

container stock)

227

51.6 (SL 

w/gloves)

8.96

0.375

60 0.0741 1,300 0.00253

Sod

Field crop, typical 350 0.432 230 0.0148

acreage8

Field crop, highacreage9 1,200

1.48

0.336 (SL 

w/gloves)

68

300 (SL 

w/gloves)

0.0504

0.25 0.987 100 0.0336

0.19 0.751 130 0.0255

0.16 0.632 160 0.0215

Chemigation application of 

dry flowable

Sod

227 8.96 0.375

Field crop, typical and 350 0.432 230 0.0148

high-acreage8,9

Nursery (ornamentals, 

vegetables, trees, 

container stock)

60 0.0741 1,300 0.00253

Groundboom application of 

a dry flowable

Golf course (fairways, 

tees, greens)

227 8.96 0.375

40 0.0494 2,000 0.00168 Field-grown 

ornamental crops

Nursery (ornamentals, 

vegetables, trees, 

container stock)

60 0.0741 1,300 0.00253

Sod

Field crop, typical 80 0.0987 1,000 0.00336

acreage8

Field crop, highacreage9 200 0.246 410 0.0084

Commercial Impregnation of Dry Flowable 

Formulation on Dry Bulk Fertilizers (closed 

system)

9.8 (EC) 0.24 (EC) 3.75 lb 

ai/ton 960 tons 0.512 200 0.0108

On-farm Impregnation of Dry Flowable 

Formulation on Dry Bulk Fertilizers 227 8.96 0.375 160 0.246 410 0.0084

Loading/applying granular 

for tractor-drawn spreader 

application

Golf course (fairways, 

tees, greens)

8.4 1.7 0.375

40 0.00183 55,000 0.000319

Sod 80 0.00365 27,000 0.000638 Christmas tree farms

Nursery (ornamentals, 

vegetables, trees, 

container stock)

60 0.00274 36,000 0.000479

Aerial application of liquid 

formulation

Nursery (ornamentals, 

vegetables, trees, 

container stock)

220 

37.6 (SL 

w/gloves)

0.219 0.375

60 0.0717 1,400 0.0000616

Sod

Field crop, typical 350 0.419 240 0.000359

acreage8

Field crop, highacreage9 1200

1.43 

0.245 (SL 

w/gloves)

70 

410 (SL 

w/gloves)

0.00123

0.25 0.957 100 0.000821
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 38 of 57

Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Sulfentrazone. 

Exposure Scenario Crop or Target

Dermal Unit 

Exposure 

(μg/lb ai)1

Inhalation Unit 

Exposure 

(μg/lb ai)1 Maximum 

Application 

Rate (lb 

ai/A)2

Area 

Treated 

(acres)3

Dermal

(LOC = 100)

Inh

(LO

Mitigation 

Level = 

baseline unless 

indicated 

otherwise

Mitigation Level 

= baseline 

unless indicated 

otherwise

Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day

0.19 0.728 140 0.000624

Chemigation application of 

a liquid formulation

Sod

220 0.219 0.375

Field crop, typical and 350 0.419 240 0.000359

high-acreage8,9

Nursery (ornamentals, 

vegetables, trees, 

container stock)

60 0.0717 1,400 0.0000616

Groundboom application of 

liquid formulation

Golf course (fairways, 

tees, greens)

220 0.219 0.375

40 0.0478 2,100 0.0000411 Field-grown 

ornamental crops

Nursery (ornamentals, 

vegetables, trees, 

container stock)

60 0.0717 1,400 0.0000616

Sod

Field crop, typical 80 0.0957 1,000 0.0000821

acreage8

Field crop, highacreage9 200 0.239 420 0.000205

Commercial Impregnation of Liquid Formulation 

on Dry Bulk Fertilizers (closed system)

8.6 

(engineering 

control)

0.083 

(engineering 

control)

3.75 lb 

ai/ton 960 tons 0.449 220 0.00374

On-farm Impregnation of Liquid Formulation on 

Dry Bulk Fertilizers 220 0.219 0.375 160 0.191 520 0.000164

Applicator

Aerial spray application

Nursery (ornamentals, 

vegetables, trees, 

container stock)

2.08

(engineering 

control)

0.0049

(engineering 

control)

0.375

60 0.000678 150,000 0.0000013

Sod

Field crop, typical 350 0.00396 25,000 0.0000080

acreage8

Field crop, highacreage9 1200 0.0136 7,400 0.0000276

Groundboom spray 

application

Golf course (fairways, 

tees, greens)

78.6 0.34 0.375

40 0.0171 5,800 0.0000638 Field-grown 

ornamental crops

Nursery (ornamentals, 

vegetables, trees, 

container stock)

60 0.0257 3,900 0.0000956

Sod

Field crop, typical 80 0.0342 2,900 0.000128

acreage8

Field crop, highacreage9 200 0.0855 1,200 0.000319

Mechanically-pressurized 

handgun

Rights-of-way (e.g., 

utilities, railroad, 

roadways)

1,300 3.9 0.019 lb 

ai/gallon

1000 

gallons 0.358 280 0.000926

Tractor-drawn Spreader 

granular application 

Golf course (fairways, 

tees, greens)

9.9 1.2 0.375

40 0.00216 46,000 0.000225

Sod 80 0.0043 23,000 0.00045 Christmas tree farms

Nursery (ornamentals, 

vegetables, trees, 60 0.00323 31,000 0.000338
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 39 of 57

Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Sulfentrazone. 

Exposure Scenario Crop or Target

Dermal Unit 

Exposure 

(μg/lb ai)1

Inhalation Unit 

Exposure 

(μg/lb ai)1 Maximum 

Application 

Rate (lb 

ai/A)2

Area 

Treated 

(acres)3

Dermal

(LOC = 100)

Inh

(LO

Mitigation 

Level = 

baseline unless 

indicated 

otherwise

Mitigation Level 

= baseline 

unless indicated 

otherwise

Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day

container stock)

Flagger

Flagger for aerial spray 

application

Nursery (ornamentals, 

vegetables, trees, 

container stock) 11 0.35 0.375

60 0.00359 28,000 0.0000985

Sod

Field crop, typical and 350 0.0209 4,800 0.000574

high-acreage9,10

Mixer/Loader/Applicator

Dry Flowables via 

Backpack

Railroad, Highway, 

Roadside, Pipeline and 

Utility Rights of-Way, 

Industrial Areas,

Fence Rows, and 

Other listed Non-crop 

Sites

8,260 2.58 0.019 lb 

ai/gallon 40 gallons 0.091 1,100 0.0000245

Landscaping, turf 

(lawns, athletic fields, 

parks, etc.)

Dry Flowables via 

Manually-Pressurized 

Handwand

Landscaping, turf 

(lawns, athletic fields, 

parks, etc.)

100,000 30 0.019 lb 

ai/gallon 40 gallons

1.1

0.00474 (SL 

w/gloves)

91

21,000 

(SL 

w/gloves)

0.000285

Dry Flowables via 

Mechanically-pressurized 

Handgun

Golf course (fairways, 

tees, greens)

Landscaping, turf 1,960 42 0.375 5 0.0533 1,900 0.000985

(lawns, athletic fields, 

parks, etc.)

Liquids via Backpack

Christmas Tree farm

8,260 2.58

0.0375 lb 

ai/gallon

40 gallons

0.18 560 0.0000484

Railroad, Highway, 

Roadside, Pipeline and 

Utility Rights of-Way, 

Industrial Areas,

Fence Rows, and 

Other listed Non-crop 

Sites

Nursery (ornamentals, 

vegetables, trees, 

container stock)

Landscaping, turf 

(lawns, athletic fields, 

parks, etc.)

0.019 lb 

ai/gallon 0.091 1,100 0.0000245

Liquids via Manuallypressurized Handwand

Landscaping, turf 

(lawns, athletic fields, 

parks, etc.)

100,000 30 0.019 lb 

ai/gallon 40 gallons

1.1

0.00474 (SL 

w/gloves)

91

21,000 

(SL 

w/gloves)

0.000285

Liquids via Mechanicallypressurized Handgun

Golf course (fairways, 

tees, greens)

Landscaping, turf 1,140 1.9 0.375 5 0.031 3,200 0.0000445

(lawns, athletic fields, 

parks, etc.)

Nursery (ornamentals, 

vegetables, trees, 

container stock)

1,300 3.9 0.0375 lb 

ai/gallon

1000 

gallons 0.707 140 0.00183

Granulars via Backpack Christmas Tree farm 15 23.8 0.375 5 0.000407 250,000 0.000112
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 40 of 57

Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Sulfentrazone. 

Exposure Scenario Crop or Target

Dermal Unit 

Exposure 

(μg/lb ai)1

Inhalation Unit 

Exposure 

(μg/lb ai)1 Maximum 

Application 

Rate (lb 

ai/A)2

Area 

Treated 

(acres)3

Dermal

(LOC = 100)

Inh

(LO

Mitigation 

Level = 

baseline unless 

indicated 

otherwise

Mitigation Level 

= baseline 

unless indicated 

otherwise

Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day

Nursery (ornamentals, 

vegetables, trees, 

container stock)

Water Soluble Packets via 

Backpack

Residential/ 

Commercial Turf

8,260 2.58

0.0033 lb 

ai/gallon 40 gallons

0.0158 13000 0.0000042

Water Soluble Packets via 

Manually-Pressurized 

Handwand

100,000 30 0.191 140000 0.0000495

Water Soluble Packets via 

Mechanically-Pressurized 

Handgun

1,350 18 0.287 lb 

ai/A 5 0.0281 11000 0.000323

1

 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2013); Level of mitigation: Baseline, Eng. 

Controls.

2

 Based on registered and proposed labels.

3

 Exposure Science Advisory Council Policy #9.1 and Registrant information.

4

 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A/day) ÷ 

BW (69 kg).

5

 Dermal MOE = Dermal NOAEL (100 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6

 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated 

(A/day) ÷ BW (80 kg).

7

 Inhalation MOE = Inhalation NOAEL (2.317, 4.661, or 8.094 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

8

 Field crops, typical acreage category covers the following crops: apples, asparagus, Brassica head and stem, Brassica leafy greens, cabbage, 

citrus fruits, tree nuts, grapes and berries, edamame, fallow cropping systems, flax, fruiting vegetables, okra, horseradish, lima beans, melons, 

rhubarb, strawberry, succulent peas, tobacco, turnips, Christmas tree farms (where applicable).

9

 Field crops, high-acreage crops category covers the following crops: corn, dry shelled peas and beans, mint, peanuts, peppermint, spearmint, 

potato, soybeans, sugarcane, sunflower, wheat. 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 41 of 57

9.2 Post-Application Risk Assessment

9.2.1 Inhalation Post-Application Risk Assessment

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for sulfentrazone at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category III) and the low vapor pressure (8 x 10-10 mm Hg). 

However, there are multiple potential sources of post-application inhalation exposure to 

individuals performing post-application 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 FIFRA SAP in December 2009, and received the SAP’s final report on 

March 2, 20107. The Agency is in the process of evaluating the SAP report as well as available 

post-application inhalation exposure data generated by the ARTF and may, as appropriate, 

develop policies and procedures, to identify the need for and, subsequently, the way to 

incorporate occupational post-application 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 post-application inhalation exposure assessment for sulfentrazone.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application inhalation exposure. Therefore, it is expected that these 

handler inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.

9.2.2 Dermal Post-Application Risk Assessment

Most of the registered uses and the proposed use on apples 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 soil-directed uses, 

post-application exposures and risks to occupational workers were not assessed. 

The registered uses on turf (golf courses and sod farms) and ornamentals are not specifically soil 

directed and, therefore, could result in potential post-application exposures. The short- and 

intermediate-term post-application exposure scenarios associated with the registered uses of 

sulfentrazone are summarized in Table 9.2.2.2. All scenarios resulted in MOEs greater than the 

LOC of 100 (ranging from 430 to 8,200) on day 0 (12 hours after application) and, therefore, are 

not of concern to HED.

 

7 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 42 of 57

Table 9.2.2.2. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Sulfentrazone.

Crop/Site Activities

Transfer 

Coefficient 

(cm2/hr)

Application

Rate (lb ai/A) DFR1 Dermal Dose(mg/kg/day)2

MOE3

(LOC = 100)

Short- and Intermediate-term

Landscape 

ornamentals 

(Container, Field 

grown 

Ornamental 

plantings)

Hand Harvesting, Hand Pruning, 

Transplanting, Hand Harvesting, Hand 

Pruning, Scouting, Container Moving, 

Hand Weeding, Transplanting, 

Pinching

230 0.375 1.05 0.028 3,200

Handset Irrigation 1,900 0.232 430

Golf Courses Maintenance, greens only 2,500

0.375 0.042

0.012 8,200

Maintenance 3,700 0.018 5,500

Sod Maintenance, Slab Harvesting, 

Transplanting/Planting 6,700 0.033 3,100

1

 DFR = Application Rate × F × (1-D)t × 4.54E8 μg/lb × 2.47E-8 acre/cm2; where F = 0.25 and D = 0.10 per day. 

2

 Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day]  BW (69 kg).

3

 MOE = POD (100 mg/kg/day) / Daily Dermal Dose. 

Restricted-Entry Interval

The REI specified on the proposed label is based on the acute toxicity of sulfentrazone. 

Sulfentrazone is classified as acute Toxicity Category III for acute oral, acute dermal, and acute 

inhalation toxicity. It is classified as Toxicity Category III for eye irritation potential and 

category IV for skin irritation potential. It is not a dermal sensitizer. Short- and intermediateterm post-application risk estimates were not a concern on day 0 (12 hours following application) 

for all post-application activities. Under 40 CFR 156.208 (c) (2) (iii), ais classified as Acute III 

or IV for acute dermal, eye irritation and primary skin irrigation are assigned a 12-hour REI. 

Therefore, the [156 subpart K] Worker Protection Statement interim REI of 12 hours is adequate 

to protect agricultural workers from post-application exposures to sulfentrazone. 

10.0 References

Recent RA

J. Van Alstine, et al., 14-JUN-2012; D389082

Scoping Document

K. Lowe, et al., 09-SEP-2009; D369064

HASPOC Memo

D. Smegal, 02-MAR-2012; TXR # 0050684; and

Re-Classification of Peer-Reviewed Developmental Neurotoxicity Study in Rats: C. Rodriguez, 

19-DEC-2011; D389975.

ORE Memo

K. Lowe, D417171; 05-JUN-2014

Dietary Memo

G. Kramer, D417172; 05-JUN-2014

cc: G. Kramer (RAB1)

RDI: RAB1 (5/14/14)

G.F. Kramer:S10957:PY-S:(703)305-5079:7509P:RAB1
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 43 of 57

Appendix A. Toxicology Profile and Executive Summaries

The requirements (40 CFR 158.340) for food uses for sulfentrazone are in Table A.1. Use of the 

new guideline numbers does not imply that the new (1998) guideline protocols were used.

Table A.1. Toxicological Data Requirements for Sulfentrazone.

Study Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity ..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Primary Eye Irritation....................................................

870.2500 Primary Dermal Irritation ..............................................

870.2600 Dermal Sensitization......................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)...............................................

870.3150 Oral Subchronic (nonrodent).........................................

870.3200 28-Day Dermal ..............................................................

870.3465 28-Day Inhalation..........................................................

yes

yes

yes

yes

yes

yes

yes

yes

870.3700a Developmental Toxicity (rodent)...................................

870.3700a Dermal Developmental Toxicity (rodent)......................

870.3700b Developmental Toxicity (nonrodent).............................

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Oncogenicity (rat)..........................................................

870.4200b Oncogenicity (mouse)....................................................

870.4300 Chronic/Oncogenicity....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial.....................

870.5300 Mutagenicity—Gene Mutation - mammalian................

870.5xxx Mutagenicity—Structural Chromosomal Aberrations...

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)...............................

870.6100b 90-Day Neurotoxicity (hen)...........................................

870.6200a ACN Screening Battery (rat) .........................................

870.6200b 90-Day Neurotoxicity Screening Battery (rat)...............

870.6300 Develop. Neurotoxicity .................................................

no

no

yes

yes

no

--

--

yes

yes

--

870.7485 General Metabolism ......................................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity .............................................................

yes

no

yes

yes

--

yes

Table A.2. 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

Table A.3. Toxicity Profile for Sulfentrazone
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 44 of 57

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 Hct, HGB, MCV, 

and MCH 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, HGB, Hct, and severity of splenic 

micropathology (increased incidence and severity 

of extramedullary hematopoiesis). Four-week 

recovery period reversed all the treatment related 

effects except extramedullary hematopoiesis; 

however, severity was reduced.

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 body-weight gains during first 5 weeks of 

study; decreased HGB, Hct, MCV, and MCH

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.

870.3465

26-Day inhalation toxicity 

with 28 days of recovery 

(rat)

49253902 (2013)

Acceptable/Non-Guideline

0, 0.085, 0.256 and 1.71 

mg/L

(0, 20, 40, 600 mg/kg/day 

[M/F])

NOAEL = 0.256 mg/L.

LOAEL = 1.71 mg/L based on significant reduction 

in RBC parameters, including RBC count, HGB, 

Hct, MCV, MCH, and/or reticulocytes in male and 

female rats following 26 days inhalation exposure 

to the test material. 

Portal-of-entry NOAEL = 0.256 mg/L.

Portal-of-entry LOAEL = 1.71 mg/L based on an 

increased incidence of minimal nasal respiratory 

epithelial hyperplasia in male and female rats. 

870.3700a

Prenatal Developmental 

(rat)

42932104 (2013)

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.
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 45 of 57

Table A.3. Toxicity Profile for Sulfentrazone

Guideline No./

Study Type

MRID No. 

(year)/Classification/ Doses Results

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).

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

Two-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.

870.3800 43869101(1995) Systemic/Developmental Toxicity NOAEL = 20 (F) 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 46 of 57

Table A.3. Toxicity Profile for Sulfentrazone

Guideline No./

Study Type

MRID No. 

(year)/Classification/ Doses Results

One-Generation 

reproduction and fertility 

effects (rat)

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

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 two-generation 

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 HGB and Hct 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%), HGB, Hct, MCV, and MCH. 

Increased nucleated red blood cells and 

reticulocytes in bone of females at 124.7 

mg/kg/day.

No evidence of carcinogenicity.

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 

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.
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 47 of 57

Table A.3. Toxicity Profile for Sulfentrazone

Guideline No./

Study Type

MRID No. 

(year)/Classification/ Doses Results

technical (94.2%) in nonactivated dose ranges of 424-

1308 ug/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).

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 

maximum tolerable dose (MTD).

870.6200 ACN 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 SCN 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

Phenyl14C sulfentrazone 

(98% pure.) was 

administered to SpragueDawley rats (five

animals/sex/dose) by gavage 

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 HMS (84-104% of 

the administered dose). In the feces, HMS 

accounted for 1.26-2.55% of the administered dose. 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 48 of 57

Table A.3. Toxicity Profile for Sulfentrazone

Guideline No./

Study Type

MRID No. 

(year)/Classification/ Doses Results

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).

The proposed metabolic pathway appeared to be 

conversion of the parent compound mainly to HMS 

(excreted in the urine). A small amount of HMS 

was also converted to sulfentrazone 3-carboxylic 

acid (excreted in the urine and feces).

870.7800 Immunotoxicity 

(rat)

48748601 (2012)

Acceptable/Guideline

0, 500, 1000, or 2000 ppm (0, 

42, 87, or 163 mg/kg/day[F])

Systemic NOAEL = 1000 ppm (87 mg/kg/day).

Systemic LOAEL = 2000 ppm (163 mg/kg/day) 

based on reduced body weight, and increased 

absolute and relative spleen weights.

Immunotoxicity NOAEL = 2000 ppm (equivalent 

to 163 mg/kg/day).

Immunotoxicity LOAEL was not established.

Published literature 47749201 (2009)

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 nonguideline 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. 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 49 of 57

Appendix B. Methodologies for HEC Calculations.

The RfC methodology applies a dosimetric adjustment that takes into consideration not only the 

differences in ventilation rate (MV) but also the physicochemical properties of the inhaled 

compound, the type of toxicity observed (e.g., systemic vs. portal-of-entry) and the 

pharmacokinetic (PK) but not pharmacodynamic (PD) differences between animals and 

humans. Based on the EPA’s RfC guidance (1994), the methodology for RfCs derivation is an 

estimate of the quantitative dose-response assessment of chronic non-cancer toxicity for 

individual inhaled chemicals and includes dosimetric adjustment to account for the speciesspecific relationships of exposure concentration to deposited/delivered dose. This adjustment is 

influenced by the physicochemical properties of the inhaled compound as well as the type of 

toxicity observed (e.g., systemic vs. portal-of-entry), and takes into consideration the PK 

differences between animals and humans. Though the RfC methodology was developed to 

estimate toxicity of inhaled chemicals over a lifetime, it can be used for other inhalation 

exposures (e.g., acute and short-term exposures) since the dosimetric adjustment incorporates 

mechanistic determinants of disposition that can be applied to shorter duration of exposures 

provided the assumptions underlying the methodology are still valid. These assumptions, in turn, 

vary depending on the type of toxicity observed. Thus the derivation of a HEC for inhaled gases 

is described by the following equation:

Where:

PODstudy: Point of departure identified in the critical toxicology study

Danimal exposure: Duration of animal exposure (hrs/day; days/wk)

Danticipated exposure: Anticipated human duration of exposure (hrs/day; days/wk)

RGDR: Regional Gas Dose Ratio

Calculations used to estimate the inhalation risk to humans from aerosols are dependent not on 

the RGDR as for gases, but on the regional deposited dose ratio (RDDR). Inhalation studies 

using aerosols characterize particulate exposure by defining the particulate diameter (mass 

median aerodynamic diameter [MMAD]) and the geometric standard deviation (σg), which is 

then used to determine the RDDR. The RDDR is a multiplicative factor used to adjust an 

observed inhalation particulate exposure concentration of an animal (A) to the predicted

inhalation particulate exposure concentration for a human (H) that would be associated with the 

same dose delivered to the rth region or target tissue.

RDDRr = (RDDr/Normalizing Factor)A

 (RDDr/Normalizing Factor)H 

As with calculations for gases, the r regions and potential target tissues are the three respiratory

regions (ET, TB, PU). The RDDR is easily calculated by using a software program designed 

specifically for computing the RDDR from the MMAD and σg defined from an aerosol 

inhalation study. The values for the species-specific parameters used to calculate the RDDR are 

provided in the EPA document “Methods for Derivation of Inhalation Reference Concentrations 

and Application of Inhalation Dosimetry.”

HEC = POD *

D 

D 

*

W

W

study * RGDR animal exposure (hrs/ day)

human exposure (hrs/ day)

animal exposure (days / wk)

human exposure (days/ wk)
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 50 of 57

Regional Deposited Dose Ratio (RDDR) for Sulfentrazone

MMAD = 2.3

Sigma g = 2.0

 Body Minute 

SPECIES Weight (g) Ventilation (VE, ml) 

-----------------------------------------------------------------------------

 rat 236 171.5 

 human 70000 13800.0 

-----------------------------------------------------------------------------

 Extrathoracic 

SA (m^2) deposited fraction 

--------------------------------------------------------------------------------

 rat 15 0.439 

 human 200 0.341 

--------------------------------------------------------------------------------

RATIO 0.075 1.288

RDDR = (VE/SA)animal/(VE/SA)human * deposited fractionanimal/deposited fractionhuman

= (171.5/15)animal/(13800/200)human * 0.439/0.341

= 0.213

The magnitude of the UFs applied is dependent on the methodology used to calculate risk. The 

RfC methodology takes into consideration the PK differences but not the PD differences. 

Consequently, the UF for interspecies extrapolation may be reduced to 3X (to account for the PD 

differences) while the UF for intraspecies variation is retained at 10X. Thus, the UF when using 

the RfC methodology is customarily 30X.

B.1. HEC Calculations for Short- and Intermediate-term Residential Exposure:

Assume residents will be exposed for 24 hrs/day and 7 days/week:

HEC = NOAELstudy * (daily duration of exposureanimal/daily duration of exposurehuman) * 

(days/week of exposureanimal/days/week of exposurehuman) * RDDR

Residential Handler Outdoor HEC = 0.256 mg/L * 0.213 = 0.054 mg/L

Residential Handler Outdoor HEC = 0.256 mg/L * (5/7) * 0.213 = 0.038 mg/L

Indoor Postapp. Handler Outdoor HEC = 0.256 mg/L * (6/18) * (5/7) * 0.213 = 0.0129 mg/L

Bystander HEC = 0.256 mg/L * (6/24) * (5/7) * 0.213 = 0.00974 mg/L
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 51 of 57

Table B.1. HEC Array for Residential Risk Assessment.

Relevant Study LOAEL

(mg/L)

NOAEL

(mg/L) Da Dh Wa Wh RDDR HEC (mg/L) inter intra UF

Short-& Intermediate-Term Exposure

Inhalation – Rat

(MRID 49253902) 

26-day

ET 1.71 0.256

See equations listed 

above table 0.213

Handler/Out

door 

Postapp.-

0.054 mg/L

3 10 NA

Indoor 

Posapp.-

0.038 mg/L

Indoor 

Postapp. 

(Adults and 

Children)-

0.0013 mg/L

Bystander0.00974 

mg/L

Long-Term Exposure: Not appropriate for sulfentrazone.

Key for Array Tables

LOAEL: Lowest-observed adverse-effect level

NOAEL: No-observed adverse-effect level

Da: Daily animal exposure (hrs/day)

Dh: Anticipated daily human exposure (hrs/day)

Wa: Weekly animal exposure (days/week)

Wh: Anticipated weekly human exposure (days/week)

RRDR: Regional Deposited Dose Ratio

HEC: Human-Equivalent Concentration

inter: Interspecies extrapolation UF

intra: Intraspecies variation UF

UF: Other UF(s)

ET: Extra-thoracic region

Route-to-Route Extrapolation

More information and details in: Memo, “Route-to-Route Extrapolations” J. Whalen and H. 

Pettigrew, 10/10/98.

HED’s route-to-route extrapolation converts human and animal values from mg/L concentrations 

to mg/kg oral equivalent doses. The equation uses a single conversion factor to account for 

default body weights and respiratory volumes. An activity factor is used to account for increased 

exposure resulting from increased respiration. 

Using the HEC calculated (based upon terminal airway inflammation in males), a conversion of 

the inhalation concentration to a dose (mg/L to mg/kg/day) was conducted as follows: 

HED (mg/kg/day) = Dose (systemic HEC value, mg/L) x A x CF (L/hr/kg) x D (hours) x AF = 

mg/kg

Where: 

A = absorption: ratio of deposition and absorption in respiratory tract compared to 

absorption by the oral route.

CF = conversion factor; a L/hr/kg factor which accounts for respiratory volume and 

body weight for a given species and strain (Table 1 of J. Whalen and H. 

Pettigrew, 10/10/98).

D = duration; duration of daily animal or human exposure (hours).

AF = activity factor; animal default is 1. For humans with a ventilation rate of 16.7 
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 52 of 57

L/min, the value is 1.2.

Therefore, the residential HED for sulfentrazone is calculated as follows:

Residential Handler and Outdoor Postapplication HED: (0.05427 mg/L) x 1.2 x 11.8 

L/hr/kg x 2 hr x 1 = 1.554 mg/kg/day

B.2. HEC Calculations for Short- and Intermediate-term Occupational Exposure:

Assume workers will be in the field for 8 hrs/day and 5 days/week:

HEC = NOAELstudy * (daily duration of exposureanimal/daily duration of exposurehuman) * 

(days/week of exposureanimal/days/week of exposurehuman) * RDDR

HEC = 0.256 mg/L * (6/8) * (5/5) * 0.213 = 0.041 mg/L.

Table B.1. HEC Array for Occupational Risk Assessment.

Relevant Study LOAEL

(mg/L)

NOAEL

(mg/L) Da Dh Wa Wh RDDR HEC (mg/L) inter intra UF

Short-& Intermediate-Term Exposure

Inhalation – Rat

(MRID 49253902) 

26-day

ET 1.71 0.256 6 8 5 5 0.213 0.041 3 10 NA

Long-Term Exposure: Not appropriate for sulfentrazone.

Key for Array Tables

LOAEL: Lowest-observed adverse-effect level

NOAEL: No-observed adverse-effect level

Da: Daily animal exposure (hrs/day)

Dh: Anticipated daily human exposure (hrs/day)

Wa: Weekly animal exposure (days/week)

Wh: Anticipated weekly human exposure (days/week)

RRDR: Regional Deposited Dose Ratio

HEC: Human-Equivalent Concentration

inter: Interspecies extrapolation UF

intra: Intraspecies variation UF

UF: Other UF(s)

ET: Extra-thoracic region

Route-to-Route Extrapolation

More information and details in: Memo, “Route-to-Route Extrapolations” J. Whalen and H. 

Pettigrew, 10/10/98.

HED’s route-to-route extrapolation converts human and animal values from mg/L concentrations 

to mg/kg oral-equivalent doses. The equation uses a single conversion factor to account for 

default body weights and respiratory volumes. An activity factor is used to account for increased 

exposure resulting from increased respiration. 

Using the HEC calculated (based upon terminal airway inflammation in males), a conversion of 

the inhalation concentration to a dose (mg/L to mg/kg/day) was conducted as follows:

HED (mg/kg/day) = Dose (systemic HEC value, mg/L) x A x CF (L/hr/kg) x D (hours) x AF = 

mg/kg
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 53 of 57

Where: 

A = absorption; ratio of deposition and absorption in respiratory tract compared to 

absorption by the oral route.

CF = conversion factor; a L/hr/kg factor which accounts for respiratory volume and 

body weight for a given species and strain (Table 1 of J. Whalen and H. 

Pettigrew, 10/10/98).

D = duration; duration of daily animal or human exposure (hours).

AF = activity factor; animal default is 1. For humans, the value varies with ventilation 

rates determined by occupational/restidential scientists; 0.6 (8.3L/min), 1.2 (16.7 

L/min) and 2.1 (29 L/min)

Therefore, the occupational HED for sulfentrazone is calculated as follows:

Occupational HED, Ventilation Rate, 8.3 L/min: (0.0407 mg/L) x 1 x 0.6 x 11.8 L/hr/kg x 8 

hr = 2.317 mg/kg/day

Occupational HED, Ventilation Rate, 16.7 L/min: 0.0407 mg/L) x 1 x 1.2 x 11.8L/hr/kg x 8 

hr = 4.661 mg/kg/day

Occupational HED, Ventilation Rate, 29 L/min: (0.0407 mg/L) x 1 x 2.1 x 11.8 L/hr/kg x 8 

hr = 8.094 mg/kg/day

Based on the current sulfentrazone label, HED believes exposures can be short- (1-30 days) or 

intermediate- (1 to 6 months) term in duration. Long-term exposures are not anticipated for 

sulfentrazone based on proposed labeled uses. For the short- and intermediate-term scenarios, 

inhalation data from the 26-day inhalation rodent study was most appropriate for determining 

HECs. In the RfC methodology, different HECs may be calculated for the same experimental 

NOAEL due to the following:

1. Different algorithms are used to derive HECs for systemic versus portal-of-entry effects. 

Typically, HECs are calculated separately for systemic versus portal-of-entry effect. For 

sulfentrazone, portal-of-entry irritation was observed and, therefore, only portal-of-entry

HECs were derived. 

2. Time adjustments are traditionally needed for non-occupational (bystander) versus 

occupational exposure scenarios. Traditionally, HECs for non-occupational exposure are 

based on the number of hours an individual may be at home. Therefore, the most 

conservative estimate of hours spent at home would be 24 hours/day and 7 days/week. In 

comparison, the average workweek for an occupational worker is 8 hours/day and 5 

days/week. The HEC array table reflects the time adjustment in the calculations.
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 54 of 57

Appendix C. Physical/Chemical Properties

Table B.1. 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 102μg/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
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 55 of 57

Appendix D. International Residue Limits

Sulfentrazone (129081; 4/15/2014)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR §180.498

(a)(1) General: Compliance with the tolerance 

levels specified below is to be determined by 

measuring only the sum of 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 

metabolite HMS (N-(2,4-dichloro-5-(4-

(difluoromethyl)-4,5-dihydro-3-hydroxymethyl5-oxo-1H-1,2,4-triazol-1-

yl)phenyl)methanesulfonamide, calculated as the 

stoichiometric equivalent of sulfentrazone 

N-[2,4-dichloro-5-[4-

(difluoromethyl)-4,5-dihydro-3-

methyl-5-oxo-1H-1,2,4-triazol-1-

yl]-phenyl]methanesulfonamide, 

including the metabolite N-[2,4-

dichloro-5-[4-(difluoromethyl)-

4,5-dihydro-3-hydroxymethyl-5-

oxo-1H-1,2,4-triazol-1-

yl]phenyl]methanesulfonamide

None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex

Soybean, seed 0.05 0.05 dry soybeans

(2)Compliance with the tolerance levels specified 

below is to be determined by measuring only the 

sum of sulfentrazone (N-[2,4-dichloro-5-[4-

(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo1H-1,2,4-triazol-1-

yl]phenyl]methanesulfonamide) and its 

metabolites HMS (N-(2,4-dichloro-5-(4-

(difluoromethyl)-4,5-dihydro-3-hydroxymethyl5-oxo-1H-1,2,4-triazol-1-

yl)phenyl)methanesulfonamide) and DMS (N-

(2,4-dichloro-5-(4-(difluoromethyl)-4,5-dihydro5-oxo-1H-1,2,4-triazol-1-

yl)phenyl)methanesulfonamide, calculated as the 

stoichiometric equivalent of sulfentrazone 

N-[2,4-dichloro-5-[4-

(difluoromethyl)-4,5-dihydro-3-

methyl-5-oxo-1H-1,2,4-triazol-1-

yl]-phenyl]methanesulfonamide, 

including the metabolites N-[2,4-

dichloro-5-[4-(difluoromethyl)-

4,5-dihydro-3-hydroxymethyl-5-

oxo-1H-1,2,4-triazol-1-

yl]phenyl]methanesulfonamide 

and N-[2,4-dichloro-5-4-

(difluoromethyl)-4,5-dihydro-5-

oxo-1H-1,2,4-triazol-1-

yl]phenyl]methanesulfonamide

None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex

Asparagus 0.15 0.15

Berry and small fruit, group 13-07 0.15

Brassica, head and stem, subgroup 

5A

0.20 0.2 cabbages

Brassica, leafy greens, subgroup 5B 0.40

Corn, field, forage 0.20

Corn, field, grain 0.15

Corn, field, stover 0.30

Flax 0.15 0.15 flaxseeds

Fruit, citrus, group 10-10 0.15

Horseradish 0.20 0.2 horseradish roots

Melon, subgroup 9A 0.15

Nut, tree, group 14 0.15
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 56 of 57

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

Pea and bean, dried shelled, except 

soybean, subgroup 6C

0.15 0.15 Dry (adzuki beans, beans, 

black-eyed peas, broad beans, 

catjang seeds, chickpeas, cowpea 

seed, field peas, grain lupin, guar 

seeds, kidney beans, lablab beans, 

lentils, lima beans, moth beans, 

mung beans, navy beans, pigeon 

peas, pink beans, pinto beans, rice 

beans, southern peas, tepary 

beans, urd beans)

Pea, succulent 0.15

Peanut 0.20

Peanut, meal 0.40

Peppermint, tops 0.30 0.3

Pistachio 0.15

Rhubarb 0.15

Spearmint, tops 0.30 0.3

Sugarcane, cane 0.15

Sugarcane, molasses 0.20

Sunflower subgroup 20B 0.20 0.2 sunflower seeds

Turnip, roots 0.15

Turnip, tops 0.60

Vegetable, fruiting, group 8-10 0.15

Vegetable, soybean, succulent 0.15

Vegetable, tuberous and corm, 

subgroup 1C

0.15

US Canada Mexico1 Codex

(c) Compliance with the tolerance levels 

specified below is to be determined by measuring 

only the sum of sulfentrazone (N-[2,4-dichloro-5-

[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo1H-1,2,4-triazol-1-

yl]phenyl]methanesulfonamide) and its 

metabolites HMS (N-(2,4-dichloro-5-(4-

(difluoromethyl)-4,5-dihydro-3-hydroxymethyl5-oxo-1H-1,2,4-triazol-1-

yl)phenyl)methanesulfonamide) and DMS (N-

(2,4-dichloro-5-(4-(difluoromethyl)-4,5-dihydro5-oxo-1H-1,2,4-triazol-1-

yl)phenyl)methanesulfonamide, calculated as the 

stoichiometric equivalent of sulfentrazone in or 

on the following commodities

None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex

Bean, lima, succulent 0.15

Cowpea, succulent 0.15

Wheat, forage 0.50

Wheat, grain 0.15 0.15 grain, cereal, group 15, 

except sweet corn; bran

Wheat, hay 0.30

Wheat, straw 1.5
Sulfentrazone Preliminary Human-Health Risk Assessment D410365

____________________________________________________________________________________________

Page 57 of 57

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

US Canada Mexico1 Codex

(d) Indirect or inadvertent residues. Compliance 

with the tolerance levels specified below is to be 

determined by measuring only the sum of 

sulfentrazone (N-[2,4-dichloro-5-[4-

(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo1H-1,2,4-triazol-1-

yl]phenyl]methanesulfonamide) and its 

metabolites HMS (N-(2,4-dichloro-5-(4-

(difluoromethyl)-4,5-dihydro-3-hydroxymethyl5-oxo-1H-1,2,4-triazol-1-

yl)phenyl)methanesulfonamide) and DMS (N-

(2,4-dichloro-5-(4-(difluoromethyl)-4,5-dihydro5-oxo-1H-1,2,4-triazol-1-

yl)phenyl)methanesulfonamide, calculated as the 

stoichiometric equivalent of sulfentrazone 

None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex

Grain, cereal (excluding sweet 

corn), Hulls

0.30

Grain, cereal, forage, fodder and 

straw, group 16, except sweet corn;

forage

0.2

Grain, cereal, forage, fodder and 

straw, group 16, except sweet corn; 

hay

0.2

Grain, cereal, forage, fodder and 

straw, group 16, except sweet corn; 

stover

0.1

Grain, cereal, forage, fodder and 

straw, group 16, except sweet corn; 

straw

0.6

Grain, cereal, group 15, except 

sweet corn

0.1

Grain, cereal, group 15, except 

sweet corn; bran

0.15

Completed: M. Negussie; 04/16/14

1 Mexico adopts U.S. tolerances and/or Codex MRLs for its export purposes.