### Sulfentrazone Human

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## Page 3 of 54 Table of Contents

1.0 Executive Summary

................................ ................................ ................................ ............. 5 2.0 HED Recommendations

................................ ................................ ................................ ...... 7 2.1 Data D eficiencies/Conditions of Registration

................................ ................................ .. 7 2.2 Tolerance Considerations

................................ ................................ ................................ . 9 2.2.1 Enforcement Analytical Method

................................ ................................ .................. 9 2.2.2 International Harmonization

................................ ................................ ......................... 9 2.2.3 Recommended Tolerances

................................ ................................ ............................ 9 2.2.4 Revisions to Petitioned

- For Tolerances

................................ ................................ ...... 10 2.3 Label Recommendations

................................ ................................ ................................ 10 2.3.1 Recommendations from Residue Reviews

................................ ................................ . 10 2.3.2 Recommendations from Occupational Assessment

................................ ................... 11 3.0 Introduction

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

................................ ................................ ................................ ........... 11 3.2 Physical/Chemical Characteristics

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

................................ ................................ ................................ ...... 12 3.4 Anticipated Exposure Pathways

................................ ................................ ..................... 17 4.0 Hazard Characterization and Dose

- Response Assessment

................................ ................ 18 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

................................ ................................ .......................... 2 0 4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

............. 21 4.4.4 Residual Uncertainty in the Exposure Database

................................ ......................... 21 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 Recommendati on

................................ .. 23 4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human

- Health Risk Assessment

................................ ................................ ................................ ................................ 23 5.0 Dietary Exposure and Risk Assessment

................................ ................................ ............ 24 5.1 Metabolite/Degradate Residue Profile

................................ ................................ ........... 24 5.1.1 Summary of Plant and Animal Metabolism Studies

................................ .................. 24 5.1.2 Residues of Concern Summary and Rational e

................................ ........................... 25 5.2 Food Residue Profile

................................ ................................ ................................ ...... 25 5.3 Water Residue Profile

................................ ................................ ................................ .... 26 5.4 Dietary Risk Assessment

................................ ................................ ................................ 27 5.4.1 Description of Residue Data Used in Dietary Assessment

................................ ......... 27 5.4.3 Acute Dietary Risk Assessment

................................ ................................ ................. 27 5.4.4 Chronic Dietary Risk Assessment

................................ ................................ .............. 27 5.4.5 Cancer Dietary Risk Assessment

................................ ................................ ................ 28 5.4.6 Summary Table

................................ ................................ ................................ ........... 28 6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

................................ .... 28 6.1 Residential Handler Exposure

................................ ................................ ........................ 28

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## Page 4 of 54 6.2 Post

- Application Exposure

................................ ................................ ............................. 31
6. 3 Combined Exposure

................................ ................................ ................................ ....... 32 6.4 Residential Bystander Post

- application Inhalation Exposure

................................ ........ 35 6.5 Spray Drift

................................ ................................ ................................ ...................... 35 7.0 Aggregate Exposure/Risk Characterization

................................ ................................ ....... 35 7.1 Acute Aggregate Risk

................................ ................................ ................................ .... 36 7.2 Short

- and Intermediate

- Term Aggregate Risk

................................ .............................. 36 7.3 Chronic Aggregate Risk

................................ ................................ ................................ . 37 7.4 Cancer Aggregate Risk

................................ ................................ ................................ ... 37 8.0 Cumulative Exposure/Risk Characterization

................................ ................................ ..... 38 9.0 Occupational Exposure/Risk Characterization

................................ ................................ .. 38 9.1 Short

- /Intermediate

- Term Handler Risk

................................ ................................ ........ 38 9.2 Short

- /Intermediate

- Post

- application Risk

................................ ................................ ..... 43 9.2.1 Dermal Post

- application Risk

................................ ................................ ..................... 43 9.2.2 Inhalation Post

- application Risk

................................ ................................ ................. 43 10.0 References

................................ ................................ ................................ .......................... 44 Appendix A. Toxicology Profile

................................ ................................ ................................ . 45 Appendix B. Physical/Chemical Properties

................................ ................................ ................. 49 Appendix C. Summary of Residue Data

................................ ................................ ...................... 50 Appendix D. Review of Human Research

................................ ................................ ................... 54

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## Page 5 of 54 1.0 Executive Summary

This assessment evaluates the petitions submitted by Interregional Research Project No. 4 (IR

- 4; PP# 1E7890 & 2E8020) and FMC (PP# 1F7838) that propose new tolerances for residues of sulfentrazone and its metabolites HMS and DMS in/on rhubarb, turnip roots and tops, sunflower subgroup 20B, succulent cowpea, succulent lima bean, succulent vegetable soybean, wheat (Spring), citrus fruit group 10

- 10, low

- growing berry group 13

- 07, tree nut group 14 and pistachios, and nongrass animal feeds crop group 18. This assessment also evaluates the potential for enhanced sensitivity of infants and children, as required under the Food Quality Protection Act (FQPA) of 1996.

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

- of

- action for controlling emerging weeds is by protoporphyrinogen oxidase (PPO) inhibition. Sulfentr azone acts by the same mechanism as the diphenyl ether herbicides in which membrane disruption is initiated by the inhibition of PPO in the chlorophyll biosynthetic pathway and leads to the subsequent build

- up of toxic intermediates. Plants emerging from soils treated with sulfentrazone turn necrotic and die shortly after exposure to light.

The sulfentrazone end

- use products (EPs) relevant for this registration request include Spartan ® 

## Herbicide [EPA Reg. No. 279

- 3189; 75% dry

- flowable (DF) formulation] a nd Spartan ® 

## 4F Herbicide [EPA Reg. No. 279

- 3220; 4 lb/gal flowable

- concentrate (FlC) formulation ]. The petitioners request the amendment of these EP labels to incorporate new uses on rhubarb, turnips, sunflower subgroup 20B , succulent cowpea (regional reg istration, limited to TN) , lima bean (regional registration, limited to TN), succulent vegetable soybean, wheat (regional registration, limited to the Pacific Northwest), citrus fruit group 10

- 10, low

- growing berry group 13

- 07, tree nut group 14, clover, alfalfa, and pistachios. These EPs are proposed for maximum seasonal rates of 0.1875

- 0. 375 lb ai/A using ground or aerial equipment with pre

- harvest intervals (PHIs) as low as 3 days.

Hazard Assessment Sulfentrazone inhibits the enzyme PPO in target plants, and the results of mammalian toxicity studies were consistent with this mode of acti on, 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 ac ross 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 cau sed 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 and at doses that were not maternally toxic, although clear no

- observed adverse

- effect levels (NOAELs) were attained in both studies. In the 2

- generation reproduction study in rats, offspring effects such as decreased body weights and decreased litte r survival were observed at doses that were maternally toxic (decreased body weight during gestation in both generations).

Although sulfentrazone is considered a developmental toxicant, the developing nervous system is not considered a selective target. A published non

- guideline developmental neurotoxicity study in the rat by De Castro et al. (2007; MRID 47749201) with no established NOAEL failed to

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## Page 6 of 54 demonstrate conclusively developmental neurotoxicity and yielded developmental effects more related to thos e observed in the rat 2

- generation reproductive toxicity study for which a clear NOAEL was established. Acute and subchronic neurotoxicity studies with well

- defined NOAELs indicate neurotoxic effects (e.g., an increased incidence of clinical signs of toxi city and motor activity changes) at relatively high administered doses [lowest

- observed adverse

- effect levels (LOAELs) of 750 mg/kg and 150(M)/180(F) mg/kg/day for acute and subchronic studies, respectively] that are more consistent with systemic toxicity rather than neurotoxicity. Furthermore, there is no evidence of neuropathology in any of the studies available for sulfentrazone. 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 Residue Profile Tolerances are currently established for residues of sulfentrazone and its metabolites under 40 CFR §180.498. The nature of the residue in plants and livestock is adequately u nderstood. There is an adequate residue analytical method for the purposes of tolerance enforcement. The submitted field trial residue data for turnip (roots and tops), rhubarb, wheat (grown in the Pacific Northwest only), tree nut group 14, citrus fruit group 10

- 10, and the berry and small fruit group 13

- 07 are 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 c oncern using validated data

- collection methods. The storage intervals were also validated. Use of the Organization for Economic Co

- operation and Development (OECD) tolerance

- calculation procedures and the submitted residue data sets indicates that reques ted tolerance levels are not appropriate for several commodities (Section 2.2.3). A revised Section F is requested. For clover and alfalfa, additional residue data and a ruminant feeding study are required; therefore, these uses should be removed from th e labels. The previously submitted residue data for sunflower seed are adequate to support the proposed crop subgroup tolerance for the combined residues of sulfentrazone, DMS, and HMS of 0.20 ppm in/on sunflower, subgroup 20B. The established tolerances for the combined residues of sulfentrazone and its two metabolites of 0.15 ppm for pea, succulent, and bean, lima, succulent are being extrapolated to cowpea, succulent and soybean, vegetable, succulent. Pending submission of a revised Section B, analyti cal reference standards for sulfentrazone and DMS (see requirements under Submittal of Analytical Reference Standards), and a revised Section F, there are no residue chemistry issues that would preclude granting unconditional registrations for the requeste d uses of the commodities listed in Table 2.2.3.

Exposure/Risk Assessment Characterization Acute and chronic risk assessments were conducted for dietary exposure based on the existing and proposed uses. The acute and chronic assessments directly incorp orated drinking water estimates. The acute and chronic (food and drinking water) analyses also assumed tolerance

level residues for all commodities, 100% crop treated (%CT), and DEEM (ver. 7.81) default processing factors. All exposure and risk estimate s were not of concern. A cancer dietary assessment was not conducted because sulfentrazone is classified as “not likely to be carcinogenic to humans.”

The proposed uses will not result in residential exposure; however, the currently registered turf use h as been reassessed to reflect updates to HED’s 2012 Residential Standard Operating Procedures (SOPs). The residential exposures estimates were revised since they impact the

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## Page 7 of 54 aggregate assessment for sulfentrazone. Since the levels of concern (LOC) for der mal exposure [margins of exposure (MOEs) <100] and inhalation exposure (MOEs <1000) are different, a total aggregated

- risk index (ARI) approach was used for residential handlers. The combined dermal and inhalation exposure risk estimates for residential h andlers are not of concern (i.e., ARI >1) at baseline for all scenarios. Residential dermal and incidental oral post

- application risk estimates were greater than the LOC of 100 and, also, are not of concern.

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; therefor e, the exposure estimates provided in the dietary exposure analysis represent acute and chronic aggregate exposure, respectively. Short

- and intermediate

- term 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 so il ingestion. The LOCs for oral exposure (MOEs <100) and inhalation exposure (MOEs <1000) are different; therefore, a total ARI approach was used to aggregate adult oral, dermal, and inhalation exposures. For children, aggregate MOEs were calculated for dermal and oral exposures. The aggregate short

- and intermediate

- term ARIs are >1 for adults and the aggregate MOEs are >100 for children; therefore, aggregate exposures to sulfentrazone are not of concern to HED.

The occupational handler and post

- application assessments were completed assuming the maximum label application rate. The proposed labels allow for application via aerial equipment, groundboom equipment, chemigation equipment, or impregnated onto dry bulk fertilizer. Based on the proposed use pattern, the duration of exposure is expected to be short

- term (1 to 30 days). Intermediate

- term exposures are less likely; however, the short

- and intermediate

- term PODs are the same. Therefore, short

- term estimat ed risk estimates are protective of intermediate

- term
exposures. Long

- term exposures (greater than 6 months) are not anticipated based on the proposed use pattern. The sulfentrazone product labels direct mixers, loaders, applicators and other handlers to a wear a long

- sleeved shirt and long pants, chemical

- resistant gloves, and shoes plus socks. Several revisions are required for the proposed labels (e.g., additional personal protective equipment; see Section 2.3.2) to ensure that exposure and risk estim ates are not of

concern.

Establishment of the tolerances recommended in Table 2.2.3 pose no specific concerns for environmental justice. This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed t o a pesticide or other chemical. Additional details regarding this can be found in Appendix D.

2.0 HED Recommendations

2.1 Data Deficiencies/Conditions of Registration

Pending resolution of the deficiencies outlined below, there are no other residue chemistry, toxicology, occupational, or residential data deficiencies that would preclude establishing permanent tolerances, as identified in Section 2.2.3.

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## Page 8 of 54 870.3465 28

- day Inhalation Study

The Hazard and Science Policy Council (HASPOC) concluded, base d on a weight

- of

evidence (WOE) approach, that a 28

- day inhalation toxicity study is required. It is recommended that the registrant submit an inhalation study protocol for Agency review prior to conducting the study.

860.1200 Directions for Use

As a ruminant feeding study and additional clover residue data are required to support use on nongrass animal feeds crop group 18, these proposed uses should be removed from the labels, as described in Sections 2.2.4 and 2.3.1. The labels should be updated for the following scenarios because additional PPE (beyond what is currently on the labels) is required to reach MOEs that are not of concern: (1) mixing/loading DFs for chemigation and groundboom applications requires the addition of gloves and a PF5 re spirator; (2) mixing/loading/applying liquids for soil

directed applications with mechanically

- pressurized handgun requires the addition of gloves and a PF5 respirator; and (3) mixing/loading DFs for aerial application requires the addition of gloves and a PF10 respirator. For the dry bulk fertilizer applications, mixing/loading DFs for commercial impregnation of dry bulk fertilizers results in risk estimates of concern using surrogate closed mixing/loading exposure data and assuming 960 tons treated daily. Chemical

specific use data could be submitted to refine the assessment.

860.1550 Proposed Tolerances

A summary of the recommended tolerance levels along with recommendations for commodity definitions are presented in Section 2.2.3. The petitioner is r equired to submit a revised Section F to reflect the recommendations in Section 2.2.3.

860.1650 Submittal of Analytical Reference Standards

The standards for sulfentrazone and DMS will soon expire (10/1/2012 and 5/1/2012, respectively). The registrant s hould either recertify the lot in the repository and send an updated certificate of analysis (COA), or submit new standards (different lot #) if the previous lots will not be recertified. If new standards are being submitted, they should be sent to the An alytical 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.)

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## Page 9 of 54 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 c ompleted 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 Administrati on (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 succes sfully recovered by the FDA MRMs.

Samples of raw agricultural and processed commodities 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. Th e 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 International Harmonization

With the exception of sunflower seed (Canada only), no Codex, Canadian, or Mexican maximum residue limits (MRLs) have been established for sulfentrazone on the subject crops. The Canadian residue definition and the MRL level for sunflower seed are the same as the U.S. recommended tolerances. Therefore, h armonization of MRLs and U.S. tolerances is not an issue at this time.

2.2.3 Recommended Tolerances

Table 2.2.3 is a summary of the proposed and HED

- recommended tolerances under 40 CFR §180.498(a)(2) for “combined residues of the free and conjugated form s 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

- (difluorom ethyl)

- 4,5

- dihydro

- 3

- methyl

- 5

- oxo

- 1 H

- 1,2,4

- triazol

- 1

- yl]phenyl]methanesulfonamide) and its metabolites HMS ( N

- (2,4

- dichloro

- 5

- (4

- (difluoromethyl)

- 4,5

- dihydro

- 3

- hydroxymethyl

- 5

- oxo

- 1 H

- 1,2,4

- triazol

- 1

- yl)phenyl)methanesulfonamide) and DMS ( N

- (2,4

- dichloro

- 5

- (4

- (difluoromethyl)

- 4,5

- dihydro

- 5

-

oxo

- 1 H

- 1,2,4

- triazol

- 1

- yl)phenyl)methanesulfonamide, calculated as the stoichiometric equivalent of sulfentrazone in or on the following commodities.”

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## Page 10 of 54 Table 2.2.3. Tolerance Summary for Sulfentrazone.

Commodity Proposed Tolerance (ppm) HED

Recommended Tolerance (ppm) Correct Commodity

Definition/Comments

Establish under 40 CFR §180.498(a)(2):
Rhubarb 0.2 0.15

- Turnip (roots) 0.2 0.15 Turnip, roots Turnip (tops) 0.7 0.60 Turnip, tops Sunflower subgroup 20B 0.2 0.20

- Vegetable soybean 0.15 0.15 Vegetable

, soybean, succulent Citrus Fruit Crop Group 10

- 10 0.15 0.15 Fruit, citrus, group 10

- 10

Low Growing Berry Crop Group 13

- 07 0.15 0.15 Berry, low growing, group 13

- 07

Tree Nut Crop Group 14 0.15 0.15 Nut, tree, group 14
Pistachio 0.15 0.15

- Alfalfa, forage 5 tbd

Additional residue data and a ruminant feeding study are required. Alfalfa, hay 20 tbd Alfalfa, seed 3 tbd Clover, forage 5 tbd Clover, hay 20 tbd Clover, seed 3 tbd
Establish under 40 CFR §180.498(c) Tolerances with regional registrations: Wheat, forage 0.45 0.50

- Wheat, hay 0.20 0.30

- Wheat, grain 0.20 0.15

- Wheat, straw 1.4 1.5

- Cowpea, succulent 0.15 0.15

- Bean, lima, succulent 0.15 0.15

- Remove from 40 CFR §180.498(a)(2): Sunflower, seed

- - - Strawberry

- - - Bean, lima, succulent

- - - Remove from 40 CFR §180.498(b): Flax, seed

- - - Strawberry

- - -



## 2.2.4 Revisions to Petitioned

- For Tolerances

Based on the proposed uses and the submitted data, HED concluded that crop group tolerances were appropriate. The HED

- recommended tolerances are based on the submitted field trial data and the OECD tolerance calculation procedures. Additional data are re quired to establish tolerances for residues of sulfentrazone in/on the nongrass animal feeds crop group 18; therefore HED cannot recommended a tolerance for residues in/on this crop group.

2.3 Label Recommendations

2.3.1 Recommendations from Residue Re views

The use directions are adequate to allow HED to assess whether the submitted residue data reflect the maximum residues likely to occur. As a ruminant feeding study and additional clover residue data are required to support the uses on nongrass anim al feeds crop group 18, HED could

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## Page 11 of 54 not recommend tolerances for this crop group; therefore, these proposed uses should be removed from the labels. A revised Section B is required.

2.3.2 Recommendations from Occupational Assessment

For occupational handl ers, the combined dermal and inhalation exposure risk estimates are not of concern (i.e., ARIs >1) at baseline (i.e., single layer of clothing, no gloves, and no respirator) for all scenarios, except the following which require additional PPE (beyond what is currently on the labels) to reach MOEs that are not of concern: (1) mixing/loading DFs for chemigation and groundboom applications requires the addition of gloves and a PF5 respirator; (2) mixing/loading/applying liquids for soil

- directed applications with mechanically

- pressurized handgun requires the addition of gloves and a PF5 respirator; and (3) mixing/loading DFs for aerial application requires the addition of gloves and a PF10 respirator.

For the dry bulk fertilizer applications, mixing/loading D Fs for commercial impregnation of dry bulk fertilizers results in risk estimates of concern using surrogate closed mixing/loading exposure data and assuming 960 tons treated daily. The estimate for the amount treated is based on use data submitted previou sly for another chemical and is the best data currently available to HED. Chemical

- specific use data could be submitted to refine the assessment.

3.0 Introduction

3.1 Chemical Identity

Table 3.1. 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

- 1 H

- 1,2,4

- triazol

1

- yl)methanesulfonanilide

CAS name N

- (2,4

- dichloro

- 5

- (4

- (difluoromethyl)

- 4,5

- dihydro

- 3

- methyl

- 5

- oxo

- 1 H

- 1,2,4

- triazol

- 1

- yl)phenyl)methanesulfonamide CAS registry number 122836

- 35

- 5

End

- use product (EP) 4 lb/gal FlC formulation (Spartan ® 

### 4F Herbicide; EPA Reg. No. 279

- 3220) and 75% DF formulation (Spartan ® 

### Herbicide; EPA Reg. No. 279

- 3189)

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## Page 1 2 of 54 Table 3.1. Nomenclature for Sulfentrazone and its Metabolites

. Chemical structure of DMS metabolite

Common name 3

- desmethyl sulfentrazone; DMS

Chemical name N

- (2,4

- dichloro

- 5

- (4

- (difluoromethyl)

- 4,5

- dihydro

- 5

- oxo

- 1 H

- 1,2,4

- triazol

- 1

- yl)phenyl)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

- 1 H

1,2,4

- triazol

- 1

- yl)phenyl)methanesulfonamide



## 3.2 Physical/Chemical Characteristics

In general, sulfentrazone is persistent and mobile. It has a 545

- day aerobic soil half

- life 1 

## an d 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 p ressure of 8 x 10 - 10 

## mm Hg. A detailed description of the physicochemical properties of sulfentrazone is provided in Appendix
B.

3.3 Pesticide Use Pattern

The use directions are adequate to allow HED to assess whether the submitted residue data reflect the maximum residues of sulfentrazone likely to occur. As a ruminant feeding study and additional clover residue data are required to support the proposed uses on nongrass animal feeds crop group 18, HED cannot recommend a tolerance for residues of sulfe ntrazone in/on crop group 18 at this time. Therefore, these proposed uses should be removed from the labels. Otherwise, the available field trial data support the proposed use directions.

A list of the sulfentrazone end

- use products relevant to this registration request is presented in Table 3.3.1. The proposed crop use directions are summarized in Table 3.3.2. Information

1 

### 90 th 

### percentile upper confidence interval of the mean half

- life.

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## Page 13 of 54 regarding rotational crop restrictions is listed in Table 3.3.3. The recommended modifications to the labels can be found in Section 2.3.

Table 3.3.1. Summary of Proposed End

- Use Products

.

Trade Name Reg. No. ai (% of formulation) Formulation

Type Target Crops Target Pests

Spartan ® 4F Herbicide 279

- 3220 39.6 (4 lb ai/gal) FlC Rhubarb, Turnips, Sunflower Subgroup 20B, Cowpeas, Lima beans, Wheat (Spring), Tree Nut Crop Group 14, Pistachio, Low

- Growing Berry Crop Group 13

- 07, Citrus Fruit Crop Group 10

- 10, Nongrass Animal Feeds Crop Group 18 Broadleaf, grass, and sedge weeds. Spartan ® Herbicide 279

- 3189 75 DF

F6285 4F CAL Herbicide 279

- 3370 39.6 (4 lb

ai/gal) FlC Rhubarb, Turnips, Sunflower Subgroup 20B, Wheat (Spring), Tree Nut Crop Group 14, Pistachio, Low

- Growing Berry Crop Group 13

- 07, Citrus Fruit Crop Group 10

- 10, Nongrass Animal Feeds Crop Group 18 Spartan ® Advance Herbicide 279

- 3334 5.7

( 0.56 lb ai/gal) FlC Tree Nut Crop Group 14, Pistachio, Low

Growing Berry Crop Group 13

- 07, Citrus Fruit Crop Group 10

- 10, Nongrass Animal Feeds Crop Group 18 Spartan ® Charge 279

- 3337 31.77

( 3.15 lb ai/gal) FlC Tree Nut Crop Group 14, Pistachio, Low

Growing Berry Crop Group 13

- 07, Citrus Fruit Crop Group 10

- 10, Nongrass Animal Feeds Crop Group 18 Authority ® Assist 279

- 3330 33.33

( 3.33 lb ai/gal) FlC Nongrass Animal Feeds Crop Group 18

F6482 45DF Herbicide 279

- 3340 18 DF Nongrass Animal Feeds Crop Group 18



### Table 3.3.2. Summary of Proposed Directions for Use of Sulfentrazone.

App. Timing; Type; and Equip. Formulation

(EPA Reg. No.) Application

Rates Max. #

App. per
Year Max.

Yearly App. Rate Use Directions and Limitations

Rhubarb Postemergence just prior to rhubarb plants breaking dormancy (80 ± 5 days before harvest)

Aerial, ground, chemigation, impregnated onto dry bulk fertilizer Spartan Herbicide (279

- 3189) 0.25 lb ai/A 1 0.25 lb ai/A Personal

- protective equipment (PPE) = Long

- sleeved (LS) shirt, long pants, chemical

- resistant gloves, shoes plus socks. Restricted

- entry interval (REI) = 12 hours. *General use directions: Aerial: min of 5 gallons per acre (GPA); Ground: min of 10 GPA.

* Crop

- specific directions: recommend applying minimum of 10 GPA. Dry bulk fertilizer: min of 200 lb/A. F6285 4F CAL Herbicide (279

- 3370) 0.25 lb ai/A 0.25 lb ai/A

Spartan 4F Herbicide (279

- 3320) 0.25 lb ai/A 0.25 lb ai/A

Turnip Roots and Tops Postemergence at 46

- 60 days preharvest

Aerial, ground, chemigation, impregnated onto dry bulk fertilizer Spartan Herbicide (279

- 3189) 0.25 lb ai/A 1 0.25 lb ai/A PPE = LS shirt, long pants, chemical

- resistant gloves, shoes plus socks. REI = 12 hours. *Gen eral use directions: Aerial: min of 5 GPA; Ground: min of 10 GPA. *Crop

- specific directions: F6285 4F CAL Herbicide (279

- 3370) 0.25 lb ai/A 0.25 lb ai/A

Spartan 4F Herbicide 0.25 lb ai/A 0.25 lb ai/A

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## Page 14 of 54 Table 3.3.2. Summary of Proposed Directions for Use of Sulfentrazone.

App. Timing; Type; and Equip. Formulation

(EPA Reg. No.) Application

Rates Max. #

App. per Year Max.

Yearly App. Rate Use Directions and Limitations

(279

- 3320) recommend applying in 10

- 40 GPA. Dry bulk fertilizer: min of 200 lb/A. Sunflower Subgroup 20B ( Calendula; castor oil plant; Chinese tallowtree; euphorbia; evening primrose; jojoba; niger seed; rose hip; safflower; stokes aster; sunflower; tallowwood; tea oil plant; vernonia; cultivars, varieties, and/or hybrids of these) Fall, early spring preplant, preemergence, preplant incorporated

Aerial, ground, chemigation, impregnated onto dry bulk fertilizer Spartan Herbicide (279

- 3189) 0.09

- 0.25

lb ai/A Up to 3 0.25 lb ai/A PPE = LS shirt, l ong pants, chemical

- resistant gloves, shoes plus socks. REI = 12 hours. Aerial: min of 5 GPA. Ground: min of 10 GPA. No retreatment interval (RTI) specified. Dry bulk fertilizer: min of 200 lb/A. F6285 4F CAL Herbicide (279

- 3370) 0.09

- 0.25

lb ai/A 0.25 lb ai/A

Spartan 4F Herbicide (279

- 3320) 0.09

- 0.25

lb ai/A 0.25 lb ai/A

Cowpeas, Succulent (Tennessee only) Preemergence

Ground Spartan Herbicide (279

- 3189) 0.07

- 0.188

lb ai/A Up to 3 0.188 lb ai/A PPE = LS shirt, long pants,

chemical

- resistant gloves, shoes plus socks. REI = 12 hours. Ground: min of 10 GPA. No RTI specified. Dry bulk fertilizer: min of 200 lb/A. Spartan 4F Herbicide (279

- 3320) 0.07

- 0.188

lb ai/A 0.188 lb ai/A

Lima bean, Succulent (Tennessee only) Preemergence

Ground Spartan Herbicide (279

- 3189) 0.07

- 0.188

lb ai/A Up to 3 0.188 lb ai/A PPE = LS shirt, long pants,

chemical

- resistant gloves, shoes plus socks. REI = 12 hours. Ground: min of 10 GPA. No RTI specified. Dry bulk fertilizer: min of 200 lb/A. Spartan 4F Herbicide (279

- 3320) 0.07

- 0.188

lb ai/A 0.188 lb ai/A

Wheat (Spring) (Pacific Northwest only) Preplant or preemergent at 40

- 60 days before forage cutting and 120 days before grain harvest

Aerial, ground, chemigation, impregnated onto dry bulk fertilizer Spartan Herbicide (279

- 3189) 0.188 lb

ai/A 1 0.188 lb ai/A PPE = LS shirt, long pants,

chemical

- resistant gloves, shoes plus socks. REI = 12 hours. *General use directions: Aerial: min of 5 GPA; Ground: min of 10 GPA. *Crop

- specific directions: recommend applying in 10

- 40 GPA. F6285 4F CAL Herbicide (279

- 3370) 0.188 lb

ai/A 0.188 lb ai/A

Spartan 4F Herbicide (279

- 3320) 0.188 lb

ai/A 0.188 lb ai/A

Tree Nut Crop Group 14 and Pistachio ( Almond; beech nut; Brazil nut; butternut; cashew; chestnut; chinquapin; filbert (hazelnut); hickory nut; macadamia nut; pecan; walnut, black and English) Apply as soil application to orchard floors or as uniform band application directed toward s base of the trunk of

trees

Ground, impregnated onto dry bulk fertilizer Spartan 4F Herbicide (279

- 3320) 0.125

-

0.375 lb ai/A Up to 3 0.375 lb ai/A PPE = LS shirt, long pants,

chemical

- resistant gloves, and shoes plus socks. REI = 12 hours. *General use directions: Aerial: min of 5 GPA; Ground: min of 10 GPA. PHI = 3 days. RTI = 60 days. Apply using ground equipment F6285 4F CAL Herbicide (279

- 3370) Spartan Advance Herbicide (279

- 3334) a 0.129

-

0.375 lb ai/A 0.375 lb ai/A

Spartan 0.125

- 0.375 lb

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## Page 15 of 54 Table 3.3.2. Summary of Proposed Directions for Use of Sulfentrazone.

App. Timing; Type; and Equip. Formulation

(EPA Reg. No.) Application

Rates Max. #

App. per Year Max.

Yearly App. Rate Use Directions and Limitations

Herbicide (279

- 3189) 0.375 lb

ai/A ai/A only; do not use airblast sprayer or apply by air. Avoid direct or indirect spray contact with foliage and fruit.

279

- 3334: Do not apply via chemigation. Spartan Charge (279

- 3337) 0.189

-

0.374 lb ai/A Up to 2 0.374 lb ai/A

Low

- Growing Berry Crop Group 13

- 07 (includes Grape) b Apply as soil application to orchard floors or as uniform band application directed towards base of the trunk of

trees

Ground, impregnated onto dry bulk fertilizer Spartan 4F Herbicide (279

- 3320) 0.125

-

0.375 lb ai/A Up to 3 0.375 lb ai/A PPE = LS shirt, long pants,

chemical

- resistant gloves, and shoes plus socks. REI = 12 hours. *General use directions: Aerial: min of 5 GPA; Ground: min of 10 GPA. PHI = 3 days. RTI = 60 days. Apply using ground equipment only; do not use airblast sprayer or apply by air. Avoid direct or indirect spray contact with foliage and fruit.

279

- 3334: Do not apply via chemigation. F6285 4F CAL Herbicide (279

- 3370) Spartan Advance Herbicide (279

- 3334) a 0.129

-

0.375 lb ai/A 0.375 lb ai/A

Spartan Herbicide (279

- 3189) 0.125

-

0.375 lb ai/A 0.375 lb ai/A

Spartan Charge (279

- 3337) 0.189

-

0.374 lb ai/A Up to 2 0.374 lb ai/A

Citrus Fruit Crop Group 10

- 10 c Apply as soil application to orchard floors or as uniform band application directed towards base of the trunk of

trees

Ground, impregnated onto dry bulk fertilizer Spartan 4F Herbicide (279

- 3320) 0.125

-

0.375 lb ai/A Up to 3 0.375 lb ai/A PPE = LS shirt, long pants,

chemical

- resistant gloves, and shoes plus socks. REI = 12 hours. *General use directions: Aerial: min of 5 GPA; Ground: min of 10 GPA. PHI = 3 days. RTI = 60 days. Apply using ground equipment only; do not use airblast sprayer or apply by ai r. Avoid direct or indirect spray contact with foliage and fruit.

279

- 3334: Do not apply via chemigation. F6285 4F CAL Herbicide (279

- 3370) Spartan Advance Herbicide (279

- 3334) a 0.129

-

0.375 lb ai/A 0.375 lb ai/A

Spartan Herbicide (279

- 3189) 0.125

-

0.375 lb ai/A 0.375 lb ai/A

Spartan Charge (279

- 3337) 0.189

-

0.374 lb ai/A Up to 2 0.374 lb ai/A

Nongrass Animal Feeds Crop Group 18 (Alfalfa; bean, velvet; clover (Trifolium, Melilotus); kudzu; lespedeza; lupin; sainfoin; trefoil; vetch; vetch, crown; vetch, milk)

Dormant Season Soil treatment (Fall or Winter applications preemergent to weeds)

Between cutting in

- season application (spring/summer preemergent to weeds)

– applied between cuttings as soon as possible after removal of previous hay crop and prior to significant re

growth (<6 inches) on Spartan 4F Herbicide (279

- 3320) 0.09

- 0.375

lb ai/A Up to 4 0.375 lb ai/A PPE = LS shirt, long pants,

chemical

- resistant gloves, and shoes plus socks. REI = 12 hours *General use directions: Aerial: min of 5 GPA; Ground: min of 10 GPA. 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. F6285 4F CAL Herbicide (279

- 3370) Authority Assist d (279

- 3330) 0.09

- 0.375

lb ai/A 0.375 lb ai/A

Spartan Advance Herbicide (279

- 3334) a lb ai/A 0.372 lb ai/A

Spartan 0.09

- 0.375 0.375 lb

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## Page 16 of 54 Table 3.3.2. Summary of Proposed Directions for Use of Sulfentrazone.

App. Timing; Type; and Equip. Formulation

(EPA Reg. No.) Application

Rates Max. #

App. per Year Max.

Yearly App. Rate Use Directions and Limitations

steams and crowns.

Aerial, ground, chemigation, impregnated onto dry bulk fertilizer Herbicide (279

- 3189) lb ai/A ai/A 279

- 3334: Alfalfa only. PHI = forage and hay may be harvested or grazed 21 days after application

.

279

- 3330: Do not apply via chemigation. PHI = forage and hay may be harvested or grazed 30 days after application, and crop grown for seed may be harvested as early as 41 days after application. Spartan Charge (279

- 3337) 0.09

- 0.359

lb ai/A 0.359 lb ai/A

May be applied on dormant alfalfa and sainfoin stubble as a soil treatment prior to weed emergence.

Do not apply after growth begins in spring or before growth ceases in fall

Aerial, Groundboom F6482 45DF Herbicide (279

- 3340) e 0.09

- 0.375

lb ai/A Up to 4 0.375 lb ai/A **Alfalfa and Sainfoin only.

Do not apply via chemigation. PHI = forage may be harvested or grazed 28 days after application.

a. Multiple active ingredient: co

- formulated with glyphosate isopropylamine salt. b. Amur river grape; aronia berry; bayberry; bearberry; bilberry; blackberry (including Andean blackberry, arctic blackberry,

bingleberry, black satin berry, boysenberry, brombeere, California blackberry, Chesterberry, Cherokee blackberry, Cheyenne blackberry, common blackberry, cor yberry, darrowberry, dewberry, Dirksen thornless berry, evergreen blackberry, Himalayaberry, hullberry, lavacaberry, loganberry, lowberry, Lucretiaberry, mammoth blackberry, marionberry, mora, mures deronce, nectarberr y, Northern dewberry, olallieberry, Or geon evergreen berry, phenomenalberry, rangeberry, ravenberry, rossberry, Shawnee blackberry, Southern dewberry, tayberry, youngberry, zarzamora, and cultivars, varieties and/or hybrids of these); blueberry, highbush; b lueberry, lowbush; buffalo currant; b uffaloberry; che; Chilean guava; chokecherry; cloudberry; cranberry; cranberry, highbush; currant, black; currant, red; elderberry; European barberry; gooseberry; grape; honeysuckle, edible; huckleberry; jostaberry; Juneberry (Sask atoon berry); kiwifruit, fuzzy; kiwifruit, hardy; lingonberry; maypop; mountain pepper berries; mulberry; muntries; native currant; partridgeberry; phalsa; pincherry; raspberry, black and red; riberry; salal; schisandra berry; sea buckthorn; serviceberry; s trawberry; wild raspberr y; cultivars, varieties, and/or hybrids of these.

c. Australian desert lime; Australian finger

- lime; Australian round lime; Brown River finger lime; calamondin; citron; citrus hybrids;

grapefruit; Japanese summer grapefruit; kumquat; lemon; lime; Mediterr anean mandarin; mount white lime; New Guinea wild lime; orange, sour; orange, sweet; pummelo; Russell River lime; satsuma mandarin; sweet lime; tachibana orange; Tahiti lime; tangel o; tangerine (mandarin); tangor; trifoliate orange; uniq fruit; cultivars, varieties, and/or hybrids of these. d. Multiple active ingredient product: co

- formulated with imazethapyr (6.67% ai).

e. Multiple active ingredient product: co

- formulated with metribuzin (55% ai).



### Table 3.3.3. Plantback Intervals for Use of Sulfentrazone. Rotational Crop 1 

### Plantback Interval (months)
Alfalfa 12 Barley 4 Cabbage Anytime
Canola 24 Cereal Grains (Buckwheat, Oats, Pearl Millet, Proso Millet, Teosinte, Wild Rice) 12

Corn, Field 10 Corn, Pop 18 Corn, Sweet 18
Cotton 18 Dry Shell Peas and Beans Anytime
Horseradish Anytime
Limas Anytime
Mint Anytime
Peanuts Anytime

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## Page 17 of 54 Table 3.3.3. Plantback Intervals for Use of Sulfentrazone. Rotational Crop 1 

### Plantback Interval (months)
Potatoes Anytime
Rice 10 Rye 4 Sorghum 10 2 

### Soybean Anytime Sugar Beets 36 Sugarcane Anytime
Sunflowers Anytime
Sweet Potatoes 12
Triticale 4
Tobacco Anytime
Turf Anytime
Wheat 4

1 

### For all other crops not listed, the rotation interval is a minimum of 12 months.

2 

### Sorghum

– 18

- month rotation for rates above 8.0 oz/A.



## 3.4 Anticipated Exposure Pathways

RD has requested that HED perform an assessment of human

- health risk to support the proposed new uses of sulfentrazone. Humans may be exposed to sulfentrazone through the consumption of food and drinking water containing sulfentrazone residues. Residenti al uses of sulfentrazone may result in inhalation and dermal exposures for adults, and dermal and incidental oral exposures for children. In an occupational setting, applicators may be exposed while handling sulfentrazone prior to application, as well as during application. There is also a potential for post

- application exposure for workers re

- entering treated fields.

Risk assessments have been previously prepared for the existing uses of sulfentrazone. This risk assessment considers the proposed new uses of sulfentrazone as well as existing uses, particularly for the dietary exposure assessment. The aggregate assessment considers dietary (food plus drinking water) and residential exposures.

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 Lo w

- Income Populations," (http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf. As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well

- established procedures. In line with OPP policy, HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting. Extensive da ta on food consumption patterns are compiled by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by s ubgroups based on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Wh enever appropriate, non

- dietary exposures based on home use of pesticide products and associated risks

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## Page 18 of 54 for adult applicators and for toddlers, youths, and adults entering or playing on treated areas postapplication are evaluated. Further considerations ar e 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 subgrou ps.

4.0 Hazard Characterization and Dose

- Response Assessment

Sulfentrazone belongs to a class of herbicides that inhibit PPO in target 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 mode of action involving inhibiti on of PPO.

4.1 Toxicology Studies Available for Analysis

The toxicological database for sulfentrazone is adequate for evaluation. In the last risk assessment (K. Lowe et al.

, 22

- DEC

- 2010; D364882 ), the only toxicity database deficiency noted was an immunotoxicity study, as specified in the revised 40 CFR Part 158 requirements. Since then, an acceptable (pending finalization) 28

- day rat immunotoxicity study has been submitted to the Agency. In addition, the HED HASPOC met on February 16, 2012 (TXR# 0050684 ) to evaluate the need for a repeated inhalation exposure study with sulfentrazone and concluded, based on a WOE approach, that a 28

- day rat inhalatio n study is now required.

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

In radiol abel

- based studies in the rat, sulfentrazone was well absorbed via the oral route of administration as indicated by the excretion of nearly all radioactivity in urine by 72 hours post

dosing. There was no indication of accumulation; only the carcass, live r, and bone showed detectable levels of radioactivity (<0.5% of the administered) at 72 hours post

- dosing. The pooled urinary radioactivity consisted almost entirely of a hydroxy methyl metabolite ( HMS) ; the parent chemical was not detected in urine and f ound 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 st udy 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

Based on the results of acute toxicity studies in the rat, sulfentrazone was classified as Category III (Category IV being the lowest category) for acute toxicity via the oral, dermal, and inhalation routes of exposure. It was a mild eye irritant (Categor y III), but not a dermal irritant or sensitizer.

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

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## Page 19 of 54 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 this mode of action, given that PPO is an important enzyme in the heme synthetic pathway in mammals. Disruption of heme biosynthesis was indicated by signs of anemia [decr eases in hematocrit, hemoglobin, and mean cell volume (MCV)] in mice, rats, and dogs at comparable dose levels from short

- through long

- term exposure without increasing much in severity.

Sulfentrazone caused developmental effects when administered via t he 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), increase in early resorptions (rats and rabbits), and reduction in live fetuses p er litter (rats and rabbits). Surviving rat fetuses exhibited reduced/delayed skeletal ossifications, and decreased fetal body weights were observed in both an oral and a dermal developmental toxicity study in rats at doses that were not maternally toxic. 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 2

- generation reproductive toxicity study in rats, developmental effects included an increased duration of gestation, reduced prenatal viability (fetal and litter), reduced litter size, and an increased number of stillborn pups. Pup body

- weight deficits, along with red uced pup and litter postnatal survival, were also observed. All of the developmental effects were reported in the presence of mild maternal toxicity (slightly decreased body

- weight gain, particularly in F 1 

## females).

In an acute neurotoxicity (ACN) study in rats, an increased incidence of clinical signs of toxicity (staggered gait, splayed hind limbs, and abdominal gripping), changes in functional

- observation battery (FOB) parameters, and decreased motor activity were observed at 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.

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 demonstrate conclusively developmental neurotoxicity and contains several shortc omings 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 t he rat 2

- 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 the last risk assessment (K. Lowe et al.

, 22

- DEC

- 2010; D364882) and Memo, C. Rodriguez, 19

- DE C

- 2011, 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 rabbits.

Preliminary review of a recently submitted 28

- day rat immunotoxicity study suggests that sulfentrazone does not directly target the immune system; and, there is no evidence of immunotoxicity in the rest of the toxicity database for sulfentrazone.

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## Page 20 of 54 Carcinogenicity studies in rats and mice showed no evidence of increased inc idence 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 Ri sk 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 c ells or clastogenic in male or female mice in vivo

.

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, except for the inhalation exposure scenarios for which the FQPA SF is being retained at 10X due to the lack of an appropriate inhalation toxicity study. The rationale is provided below.

4.4.1 Completeness of the Toxicology Database

The existing toxicology database for sulfentrazone is ad equate for FQPA evaluation. The following acceptable studies are available for FQPA consideration:

Developmental toxicity studies in rats and rabbits
Two

- generation reproduction study in rats Acute and subchronic neurotoxicity studies in rats

The developing nervous system is not considered a selective target of sulfentrazone’s toxicity. Therefore, the classification of the published, non

- guideline rat developmental toxicity study by DeCastro et al ., 2007 (mentioned above) as unacceptable has no impact on the completeness of the toxicity database for FQPA consideration.

In the case of inhalation exposures, t he HASPOC met on February 16, 2012 to evaluate the need for a 28

- day inhalation study in rats. The HASPOC concluded, based on a WOE approac h, that a 28

- day inhalation study in rats is required to adequately assess short

- and intermediate

- term exposure scenarios based on the currently registered labels and use pattern. As a result, an FQPA SF of 10X is being retained for inhalation exposure s cenarios due to the lack of an appropriate 28

- day rat inhalation toxicity study.

4.4.2 Evidence of Neurotoxicity

There is no concern for neurotoxicity with sulfentrazone. Evidence of neurotoxicity from both ACN and SCN studies consisted of clinical s igns in the absence of neuropathology. In addition, both ACN and SCN studies in the rat attained clear NOAELs. There is no evidence in the toxicity database that the developmental nervous system is a selective target of sulfentrazone’s toxicity and the p ublished, non

- guideline rat developmental toxicity study by DeCastro et al.

, 2007 has been classified, due to several shortcomings, as unacceptable for use in regulatory

purposes.

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## Page 21 of 54 4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young A nimal

There was evidence for increased (quantitative) susceptibility following oral and dermal exposures in the developmental toxicity studies in rats. There was no evidence of increased susceptibility in rabbits; developmental effects were seen in the presence of maternal toxicity. In the rat 2

- generation reproduction study, offspring toxicity was seen in the presence of parental/systemic toxicity. Although developmental toxicity was observed at lower doses than maternal toxicity in both oral and dermal devel opmental toxicity studies in rat, the concern is low based on the following considerations: 1) the toxicology database for assessing pre

- and post

natal susceptibility is complete; 2) there are clear NOAELs and LOAELs for the developmental effects observe d via both the oral and dermal routes; 3) the PODs used for assessing dietary and

non

- dietary (dermal and inhalation) exposure risks are based on developmental and/or offspring toxicity; and 4) there are no residual uncertainties for pre

- and/or post

- natal 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 tolerance

level 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 associate d with the lack of an appropriate inhalation toxicity study.

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 cri tical effect in the database and observed via both the oral and dermal routes of exposure.

Acute Dietary Endpoint ( Females 13

- 49 y ea rs old): This acute dietary endpoint is based on increased gestation duration, reduced pre

- /postnatal litter and pup sur vival, reduced litter size, increased number of stillborn pups, reduced postnatal survival (pups and litter), and pup body

weight deficits throughout lactation in both generations of offspring observed in the 2

- generation reproductive toxicity study in rat s. The developmental effects were reported in the presence of mild maternal toxicity (slightly decreased body

- weight gain, particularly in F 1 

## females). It has been HED’s practice to consider various forms of developmental toxicity, such as the such as

re duced 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 fe males. 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 a lso evaluated for this acute dietary endpoint. However, it was concluded that such effects are unlikely due to a single dose event and are more appropriate

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## Page 22 of 54 for a repeated

- exposure scenario. Furthermore, EPA has not traditionally considered delays in

oss ification (and related fetal body weight deficits) to be single dose effects. The conventional 100

- fold factor (10X inter

- , and 10X intra

- species) was applied to the NOAEL (14 mg/kg bw/day). The FQPA SF was not retained for this exposure scenario since t he toxicology database is complete for pre

- and/or postnatal susceptibility. Thus, the acute reference dose (aRfD) and population

- adjusted dose (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 (NOAEL = 250 mg/kg bw) seen following a single oral administration in the acute neurotoxicity stud y. The FQPA SF was not retained for this exposure scenario since the toxicology database is complete for pre

- and/or postnatal susceptibility. The aRfD and aPAD are equivalent at 2.5 mg/kg bw/day.

Chronic Dietary Endpoint ( All populations): The chroni c 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 bw in males and females , respectively (lowest NOAEL = 14 mg/kg/day for males) in the rat 2

- generation reproductive toxicity study. This study is based on the most sensitive endpoint: developmental toxicity. The FQPA SF was not retained for this exposure scenario since the toxi cology database is complete for pre

- and/or postnatal susceptibility. The chronic reference dose (cRfD) and population

- adjusted dose (cPAD) are equivalent at 0.14 mg/kg bw/day.

Incidental Oral Endpoint (Short

- and intermediate

- term): This endpoint is b ased on offspring toxicity observed in the rat 2

- 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 bw in males and females, respectively (lowest NOAEL = 14 mg/kg/day for males). The effects seen in the offspring are appropriate for the population of concern (infants and children) and durations (short

- and intermediate

- term) of exposu re. The LOC for incidental oral risk estimates is for MOEs less than 100, which includes the 10X inter

- and 10X

- intra

- species factor is adequate for this exposure scenario. The FQPA SF was not retained since the toxicology database is complete for

pre

- an d/or post

- natal susceptibility and there are no residual uncertainties.

Dermal E ndpoints ( S hort

- and intermediate

- term): This endpoint is based on developmental toxicity observed in a dermal developmental toxicity study in rats. This endpoint is appropriate since the developmental effects were seen after repeated exposure via the route of exposure of

concern

– dermal. Th e LOC for occupational and non

- occupational dermal risk estimates is for MOEs less than 100, which includes the 10X inter

- and 10X intra

- species factors. The FQPA SF was not retained since the toxicology database is complete for pre

- and/or postnatal susce ptibility and there are no residual uncertainties.

Inhalation E

ndpoints ( S hort

- and intermediate

- term) : The HED HASPOC met on February 16, 2012 (TXR# 0050684) to evaluate the need for a repeated inhalation exposure study with sulfentrazone and concluded, based on a WOE approach, that a 28

- day rat inhalation study is now required. In the absence of such study, the rat oral prenatal developmental toxicity study with an assumed 100% absorption via the inhalation route will be used along with an FQPA SF of 1 0X. The rat oral prenatal developmental toxicity study is considered protective of

### Sulfentrazone Human

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## Page 23 of 54 developmental toxicity which is the most critical effect associated with sulfentrazone. The endpoint is based on decreased mean fetal weights and retardation in skeletal d evelopment evidenced by an increased number of litters with any variation and by decreased number of caudal vertebral and metacarpal ossification sites. The LOC for occupational and non

occupational inhalation risk estimates are for MOEs less than 1000. This value includes a 10X inter

- species factor, a 10X intra

- species factor, and an additional 10X UF DB 

## to protect for the uncertainty from the oral to inhalation route

- to

- route extrapolation.

4.5.2 Recommendation for Combining Routes of Exposures for Ri sk Assessment

The Agency must consider risks from individual routes of exposure (oral, dermal, and inhalation) and perform an aggregate risk assessment if a common toxicity endpoint is established across different routes of exposure. The developmental effects (fetal bo dy

- weight deficits and skeletal effects) observed in the dermal and oral rat developmental toxicity study can be aggregated for the dermal and inhalation endpoints.

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

Occupational 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 UF A = 10X

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

aPAD = 0.14 mg/kg/day 2

- Gen Reproductive Toxicity Study

- Rat

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

UF H = 10X FQPA SF = 1X aRfD

=aPAD = 2.5 mg/kg/day Acute Neurotoxicity Study

- Rat

LOAEL = 750 mg/kg/day based on increased incidence of clinical signs and FOB parameters and decreased motor activity. Chronic Dietary (all populations) NOAEL = 14 mg/kg/day UF A = 10X

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

cPAD = 0.14 mg/kg/day 2

- Gen Reproductive Toxicity Study

- Rat

Offspring Toxicity LOAEL = 33 (M) and 40 (F) mg/kg/day based on reduced prenatal viability (fetal & litter), reduced litter size, in creased no. of stillborn pups, reduced pup and litter postnatal survival, and decreased pup body weights throughout lactation

. Short

- (1

- 30 days) and Intermediate

- Term (1

- 6 months) Incidental Oral Offspring NOAEL = 14 mg/kg/day UF A = 10X

UF H = 10X FQPA S F = 1X Residential

LOC for MOE = 100 2

- Generation Reproduction Study

- Rat

Offspring LOAEL = 33 mg/kg/day based on decreased pup body weights and reduced postnatal survival in both generations.
Short

- (1

- 30 days), Intermediate

- (1

- 6 NOAEL = 100 UF A = 10X

UF H = 10X Residential

LOC for Dermal Developmental Study

- Rat

LOAEL = 250 mg/kg/day based on decreased

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## Page 24 of 54 Table 4.5.4. Summary of Toxicological Doses and Endpoints for Sulfentrazone for Use in Residential and

Occupational Human Health Risk Assessment.

Exposure Scenario POD Uncertainty/ FQPA SFs RfD, PAD,

LOC for Risk Assessment Study and Toxicological Effects

months), and Long

Term (>6 months) Dermal mg/kg/day FQPA SF = 1X MOE = 100

Occupational LOC for MOE = 100 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 NOAEL = 10 mg/kg/day

100% inhalation absorption assumed Residential:

UF A = 10X UF H = 10X FQPA SF = 10X Residential

LOC for MOE = 1000 Occupational LOC for MOE = 1000 Pren atal Developmental Toxicity

- Rat

Developmental LOAEL = 25 mg/kg/day, based upon decreased mean fetal weights, and retardation in skeletal development evidenced by an increased number of litters with any variation and by decreased number of caudal vertebra l and metacarpal ossification sites. Occupational: UF A = 10X UF H = 10X UF DB = 10X Cancer (oral, dermal, inhalation) Classification: Sulfentrazone is classified as “not likely to be carcinogenic to humans.”

NOAEL = no

- observed adverse

- effect level. LOAEL = lowest

- observed adverse

- effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF L = extrapolation for use of a LOAEL in the absence of a NOAEL. FQPA SF = FQPA Safety Factor. PAD = population

- adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure

. LOC = level of concern.



## 5.0 Dietary Exposure and Risk Assessment

Memo, G. K ramer, 14

- JUN

- 2012; D 389972 Memo, M. Barrett, 03

- APR

- 2012; D39377 and D397770 Memo, J. Van Alstine, 14

- JUN

- 2012; D389973



## 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. K ramer, 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 s ulfentrazone following postemergent applications in corn, soybean, and radish were submitted in conjunction with the current petition. The metabolism of sulfentrazone following post

- emergent application was similar to that seen in rotational crops and fol lowing 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.

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## Page 25 of 54 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 Re sidues 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 5.1.2 below.

Table 5.1.2. Residues of Concern in Crops, Livestock, and Drink ing 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

The submitted field trial residue data for turnip (roots and tops), rhubarb, wheat (grown in the Pacific Northwest only), tree nut group 14, citrus fruit group 10

- 10, and the berry and small fruit group 13

- 07 are adequate. The field trial data r eflect 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. Using the OECD tolerance calculation procedures for the residue data sets indicate that the requested tolerance levels are not appropriate for several commodities (Table 2.2.3). A revised Section F is requested. For clover and alfalfa, additional residue data and a ruminant feeding study are required.

The previously submitted residue data for sunflower seed are adequate to support the proposed crop subgroup tolerance for the combined residues of sulfentrazone, DMS, and HMS of 0.20 ppm in/on sunflower, su bgroup 20B. The established tolerances for the combined residues of sulfentrazone and its two metabolites of 0.15 ppm for pea, succulent, and bean, lima, succulent are being extrapolated to cowpea, succulent (regional tolerance in TN) and soybean, vegetab le, succulent. Additionally, IR

- 4 has requested to amend the current tolerances in 40 CFR 180.498 in or on bean, lima, succulent at 0.15 ppm by removing the tolerance from the table in Section (a)(2) and adding the tolerance to Section (c) Tolerances with regional registrations. Acceptable residue field trials in TN are available to support a regional registration.

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## Page 26 of 54 No detectable residues were found in grapes and wheat grain treated at an exaggerated rate ( 5X ); therefore, no grape or wheat processing s tudies were conducted. The submitted citrus processing study demonstrated that sulfentrazone residues of concern do not concentrate in citrus processed fractions as a result of the proposed use. Separate tolerances are not required for wheat, grape, and citrus processed commodities.

Rotational crop studies for corn, rice, sorghum, and wheat were previously submitted in conjunction with the soybean petition (PP#4F04407). Permanent tolerances have been established for indirect or inadvertent residues of sulfentrazone and its metabolites, HMS and DMS, in cereal grains (excluding sweet corn), bran, forage, grain, hay, hulls, stover, and straw. As the 1X use rate in soybeans (0.375 lb ai/A) is greater than or equal to the 1X use rate of the proposed new us es, the established tolerances for indirect or inadvertent residues of sulfentrazone and its metabolites, HMS and DMS, are adequate to support the subject petition. The proposed rotational crop restrictions are adequate and consistent with previous sulfen trazone petitions.

Based on the available goat and poultry metabolism data and the previously calculated dietary exposures of livestock to sulfentrazone residues, HED had concluded that quantifiable residues of sulfentrazone were unlikely to occur in livestock commodities. As clover and alfalfa are significant feedstuffs for livestock ( ruminants only ), the dietary burden of sulfentrazone was recalculated for this petition using the Agency’s most recent guidance on constructing reasonably balanced live stock diets (Memo, G. Herndon, 30

- JUN

- 2008). Based upon this diet and the results of the ruminant metabolism study, a ruminant feeding study is now required.

Summary tables of the residues from the crop field trials can be found in Appendix C.

5.3 Water Residue Profile

EFED provided estimated drinking water concentrations (EDWCs) for the combined residues of sulfentrazone and its major degradate, 3

- carboxylic acid sulfentrazone, the residues of concern in drinking water (Memo, M. Barrett, 03

- APR

- 2012; D 39377 and D397770). The EDWCs were Tier 1 estimates for ground water using the Screening Concentration In Ground Water (SCI

GROW) Model and surface water using the FQPA Index Reservoir Screening Tool (FIRST) Model. EFED believes that the Tier I models us ed for these crops provide a reasonable worst

case scenario, and provide estimates suitable for screening purposes. Application rates for the new uses (up to 0.375 lbs ai/A per season) are the same as or less than what was previously assessed; the additio n of the proposed new uses does not result in changes to the exposure estimates used in the previous assessment. The EDWCs used in the current and previous assessments were based on the use of sulfentrazone on crops such as sugarcane, cabbage, potatoes, m int, or horseradish.

For surface water, the acute (peak) sulfentrazone value is 32.0 ppb and the annual average value ranges from 0.5 ppb in alkaline or neutral waters (most common) to 5.1 ppb in acidic waters. The groundwater screening sulfentrazone concentration is 15.7 ppb. For 3

- carboxylic acid sulfentrazone, the acute peak is 3.8 ppb and the an nual average is 2.7 ppb. For 3

- carboxylic acid sulfentrazone in groundwater, the concentration is 10.3 ppb. The drinking water estimates for use in human health risk assessment for sulfentrazone are shown in Table 5.3.

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## Page 27 of 54 Table 5.3 . Estimated Tier 1 Con centrations of Sulfentrazone and 3

- Carboxylic Acid Sulfentrazone in

Drinking Water Due to the Use of Sulfentrazone on Sugarcane, Cabbage, Potatoes, Mint, or Horseradish 1,2



### .
Chemical Surface Water (ug/L) Groundwater (ug/L)
Acute Chronic Acute and Chronic
Sulfentrazone 32.0 5.1 15.7
3

- Carboxylic Acid Sulfentrazone 3.8 2.7 10.3
Total 35.8 7.8 26.0

1 These crops were chosen for this assessment because the label permits use of the maximum application rate (0.375 pounds active ingredient per acre) and aerial application.

2 The bolded total values are the estimates used in the dietary risk assessment.



## 5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

Conservative unrefined acute and chronic dietary (food and drinking water) exposure assessments were performed for the general U.S. population and all population sub groups. Assumptions for these assessments included tolerance

- level residues for all commodities, 100% CT, and DEEM TM 

## 7.81 default processing factors. Drinking water estimates were provided by EFED for the combined residues of sulfentrazone and its major d egradate, 3

- carboxylic acid sulfentrazone based on the use of sulfentrazone on crops such as sugarcane, cabbage, potatoes, mint, or horseradish. The acute assessment incorporated a surface water EDWC of 0.0358 ppm, calculated using the FIRST Model, and th e chronic assessment incorporated a groundwater EDWC of 0.026 ppm, calculated using the SCI

- GROW Model.

5.4.2 Percent Crop Treated Used in Dietary Assessment

The acute and chronic dietary analyses assumed 100% CT for all commodities.

5.4.3 Acute Dietary Risk Assessment

Acute dietary risk estimates (food and drinking water) are not of concern for the general population or any other population subgroup. The highest exposure estimate was for the population subgroup children 1

- 2 years old, which ut ilized <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 children 1 to 2 years old, females 13

- 49 years old have the highest risk estimate (3% aPAD). The acute exposure estimate for the general U.S. population utilized <1% of the aPAD. A summary table of dietary exposure and risk for sulfentrazone can be found in Section 5.4.6.

5.4.4 Chroni c Dietary Risk Assessment

Chronic dietary risk estimates (food and drinking water) are not of concern for the general population or any other population subgroup. The highest exposure and risk estimates were for the population subgroup children 1

- 2 years old, which utilized 4% of the cPAD for sulfentrazone. The chronic exposure estimate for the general U.S. population utilized 2% of the cPAD. A summary table of dietary exposure and risk for sulfentrazone can be found in Section 5.4.6.

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## Page 28 of 54 5.4.5 Cancer Di etary Risk Assessment

A cancer dietary assessment was not conducted because sulfentrazone is classified as “not likely to be carcinogenic to humans.”

5.4.6 Summary Table

Table 5.4.6. Summary of Acute and Chronic Dietary (Food and Drinking Water) Exposure and Risk

for Sulfentrazone. 1

Population Subgroup 95 th Percentile cPAD (mg/kg/day) Exposure

(mg/kg/day) %cPAD aPAD (mg/kg/day) Exposure

(mg/kg/day) %aPAD

General U.S. Population

2.5 0.006238 <1.0

0.14 0.002422 1.7

All Infants (< 1 year old) 0.010530 <1.0 0.003720 2.7

Children 1

- 2 years old 0.013972 <1.0 0.005855 4.2
Children 3

- 5 years old 0.011379 <1.0 0.005258 3.8

Children 6

- 12 years old 0.007727 <1.0 0.003456 2.5

Youth 13

- 19 years old 0.005499 <1.0 0.002287 1.6

Adults 20

- 49 years old 0.004429 <1.0 0.001966 1.4 Adults 50+ years old 0.003962 <1.0 0.001838 1.3

Females 13

- 49 years old 0.14 0.004466 3.2 0.001955 1.4

1 

### The populations with the greatest risk estimates are bolded.



## 6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

Memo, K. Lowe, 17

- MAY

- 2012, D389974



## 6.1 Residential Handler Exposure

The proposed uses will not result in residential exposure; however, the currently registered turf use has been reassessed to reflect updates to HED’s 2012 Residential SOPs. The residential exposures were revised since they impact the aggregate assessment for sulfentrazone.

According to the Human

- Health Assessment Scoping Document in Support of Registration Review (Memo, K. Lowe et al

., D369064, 9/9/09), the formulations registered for use on turf include liquids, DFs, and granules at a maximum rate of 0 .375 lb ai/A. The residential handler exposure assessment estimates dermal and inhalation exposures for individuals using sulfentrazone on residential turfgrass. There are sulfentrazone labels that indicate application by

p rofessional lawncare operators only; however, a residential handler assessment has been included to cover the possibility of homeowner applications since the products are not restricted

use.

Unit exposure values and estimates for area treated were taken from HED’s 2012 Residential SO Ps: Lawns/Turf. The baseline dermal exposures assumed that residential handlers wore shorts, a short

- sleeved shirt, and no gloves, and the baseline inhalation exposures did not assume the use of a respirator.

Short

- term risk estimates for residential handlers are presented in Table 6.1. Intermediate

- term exposures are not likely because of the intermittent nature of applications by homeowners. Dermal MOEs range from 1,100 (mixing/loading/applying DFs with manually

- pressurized

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## Page 29 of 54 handwand and backpack s prayers) to 73,000,000 (loading/applying granules by cup and shaker can). Inhalation MOEs range from 6,600 (mixing/loading/applying DFs with manually

pressurized handwand and backpack sprayers) to 62,000,000 (loading/applying granules by cup and shaker ca n). The combined dermal and inhalation exposure risk estimates for residential handlers are not of concern (i.e., ARIs>1) at baseline for all scenarios. The risk estimates shown in Table 6.1 indicate that if a residential handler were to obtain the produ ct and apply it in accordance with the proposed label, then the dermal and inhalation exposure and risk estimates would not be of concern.

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## Page 30 of 54 Table 6.1. Residential Handler Exposure and Risk Estimates for Sulfentrazone Applications to Turfgrass.

Exposure Scenario Application
Rate 1 Area

Treated Daily 2 Baseline Unit

Exposures (mg/lb ai) Baseline Dose 4 (mg/kg/day) Baseline MOE 5 Dermal Risk Index 6 Inhalation

Risk Index 7 ARI 8

Dermal 3 Inhalation 3 Dermal Inhalation Dermal Inhalation
Loader/Applicator for Granules

Push

- type spreaders 0.375 lb ai/A 0.5 A 0.81 0.0026 0.0022 0.0000071 45,000 1,400,000 450 1,400 340
Belly grinders 0.375 lb ai/A 0.023 A 360 0.039 0.045 0.0000049 2,200 2,100,000 22 2,100 22
Spoon 0.375 lb ai/A 0.002 A 6.2 0.087 0.000077 0.0000011 1,300,000 9,200,000 13,000 9,200 5,400
Cup 0.375 lb ai/A 0.002 A 0.11 0.013 0.0000014 1.6E

- 07 73,000,000 62,000,000 730,000 62,000 57,000
Hand dispersal 0.375 lb ai/A 0.002 A 160 0.38 0.0020 0.0000047 50,000 2,100,000 500 2,100 400

Shaker can 0.375 lb ai/A 0.002 A 0.11 0.013 0.0000014 1.6E

- 07 73,000,000 62,000,000 730,000 62,000 57,000
Mixer/Loader/Applicator for Liquids
Manually

- pressurized handwand 0.019 lb ai/gal 5 gal 63 0.018 0.087 0.000025 1,200 400,000 12 400 12

Hose

- end sprayer 0.375 lb ai/A 0.5 A 13.4 0.022 0.036 0.000060 2,700 170,000 27 170 23
Backpack 0.019 lb ai/gal 5 gal 130 0.14 0.18 0.00019 560 52,000 5.6 52 5.1
Sprinkler can 0.375 lb ai/A 0.023 A 13.4 0.022 0.0017 0.0000027 60,000 3,600,000 600 3,600 510
Mixer/Loader/Applicator for Dry Flowables
Manually

- pressurized handwand 0.019 lb ai/gal 5 gal 69 1.1 0.095 0.0015 1,100 6,600 11 6.6 4.1

Hose

- end sprayer 0.375 lb ai/A 0.5 A 13.4 0.022 0.036 0.000060 2,700 170,000 27 170 23
Backpack 0.019 lb ai/gal 5 gal 69 1.1 0.095 0.0015 1,100 6,600 11 6.6 4.1
Sprinkler can 0.375 lb ai/A 0.023 A 13.4 0.022 0.0017 0.0000027 60,000 3,600,000 600 3,600 510
1. Application rates based on communication between the Registrant and EPA regarding the maximum rates allowed on the labels for the residential use sites. From label 279

- 3323: 0.375 lb ai/A * 20 gal/A = 0.019 lb ai/gal. 2. Based on HED’s SOPs: Lawns/Tu rf (January 2012). 0.023 A = 1000 ft 2 . 0.002 A = 100 ft 2

. 3. Baseline Dermal: Short

- sleeve shirt, shorts, and no gloves; Baseline Inhalation: no respirator. 4. Dose (mg/kg/day) = daily unit exposure (mg/lb ai) x application rate (lb ai/gal) x gal treated * body weight (69 kg). 5. MOE = NOAEL (Dermal = 100 mg/kg/day; Inhalation = 10 mg/kg/day) / daily dose (mg/kg/day). Level of concern = 100. 6. Dermal Risk Index = Dermal MOE / Dermal LOC. Dermal LOC = 100. 7. Inhalation Risk Index = Inhalation MO E / Inhalation LOC. Inhalation LOC = 1000. 8. ARI = 1 / ((1 ÷ Dermal Risk Index) + (1 ÷ (Inhalation Risk Index) )

.

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## Page 31 of 54 6.2 Post

- Application Exposure

Sulfentrazone can be used in many areas that can be frequented by the general population including residential areas (e.g., home lawns). As a result, individuals can be exposed by entering these areas if they have been previously treated. Potential expos ure scenarios, routes of exposure, and lifestages assessed include:

Physical activities on turf: adults (dermal) and children 1 < 2 years old (dermal and incidental oral); Mowing: adults (dermal) and children 11 < 16 years old (dermal); and Golfing: ad ults (dermal), children 11 < 16 years old (dermal), and children 6 < 11 years old (dermal).

The lifestages (i.e., adults, children 1<2 years old, children 11 < 16 years old, and children 6 < 11 years old) selected for each post

- application scenario are ba sed on an analysis provided as an Appendix in the 2012 Residential SOPs. These lifestages are not the only lifestages that could be potentially exposed for these post

- application scenarios; however, the assessment of these lifestages is health protective for the exposures and risks for any other potentially exposed lifestages.

Short

- term dermal and incidental oral exposures to sulfentrazone were assessed and are presented in Table 6.2. There is the potential for intermediate

- term exposure to sulfentrazon e in the soil due to its half

- life of 545 days; however, s ince the maximum yearly application rate is the same as the maximum single application rate, the short

- term assessment is protective of intermediate

- term soil ingestion exposure. The residential po st

- application scenarios were assessed using standard default assumptions and inputs from HED’s 2012 Residential SOPs. All adult and children post

- application dermal scenarios resulted in MOEs greater than the LOC (MOE = 100) for short

- term exposure. The lowest dermal MOE (370) represents children 1 < 2 years old doing physical activities on turf that had been treated with a liquid formulation of sulfentrazone. Incidental oral scenarios for children 1 < 2 years old resulted in MOEs greater than the LOC ( MOE = 100), with the lowest MOE being 1,100 for episodic granular ingestion.
Non

- dietary ingestion of granules is considered to be an episodic event and, as such, is compared to the acute dietary POD, and is not combined with other sources of exposure.

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## Page 32 of 54 Table 6.2. Short

- Term Residential Post

- application Exposure and Risk Estimates for Sulfentrazone. Lifestage Post

- application Exposure Scenario Dose (mg/kg/day) a MOEs Liquid Formulation
Adult Turf

Liquid formulation

0.375 lb ai/A Dermal Physical Activities on Turf 0.16 610 Mowing 0.0033 30,000 Golfing 0.013 7,800
Child 11 < 16 years old Dermal Mowing 0.0033 30,000 Golfing 0.013 7,700
Child 6 < 11 years old Dermal Golfing 0.015 6,600

Child 1 < 2 year old Dermal Physical Activities on Turf 0.27 370
Hand

- to

- Mouth 0.0056 2,500 Object

- to

- Mouth 0.00017 82,000
Short

- and Intermediate

- term Incidental Soil

Ingestion 1.2 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

Mowing 0.00066 150,000 Golfing 0.0026 39,000
Child 11 < 16 years old Dermal Mowing 0.00066 150,000 Golfing 0.0026 39,000
Child 6 < 11 years old Dermal Golfing 0.0030 33,000

Child 1 < 2 year old Dermal Physical Activities on Turf 0.059 1,700

Hand

- to

- Mouth 0.00055 25,000 Object

- to

- Mouth 0.00017 82,000
Short

- and Intermediate

- term Incidental Soil

Ingestion 1.2 x 10 - 5 1,100,000

0.9% ai Episodic Granular Ingestion 0.24 1,100

a. Dose equations: (1) Dermal dose = turf transferable residue (ug/cm2) * (0.001 mg/ug) * transfer coefficient (cm2/hr) * exposure time (hr/day) / body weight (kg)

. (2) Hand

- to

- mouth dose = hand residue loading (mg/cm 2 ) * fraction hand mouthed/event * surface area of hand (cm2) * exposure time (hr/day) * replenishment intervals/hr * saliva extraction factor * number of contacts per hour (events/hr) / body weight (kg)

. (3) Object

- to

- mouth dose = object residue loading (mg/cm 2 ) * surface area of object mouthed (cm 2 ) * exposure time (hr/day) * replenishment intervals/hr * saliva extraction factor * number of contacts per hour (events/hr) / body weight (kg)

. (4) Soil ingestion dose = soil residue (ug/g) * ingestion rate of soil (mg/day) * 0.000001 g/ug / body weight (kg )

. (5) Granular ingestion dose = ingestion rate of dry pesticide formulation (g/day) * fraction of ai in dry formulation * 1000 mg/g)

. b. MOE = POD (mg/kg/day) / Dermal or incidental oral dose (mg/kg/day), where dermal POD = 100 mg/kg/dat; incidental oral POD = 14 mg/kg/day; acute dietary POD = 250 mg/kg/day.



## 6.3 Combined Exposure

HED combines risk estimates resulting from separate exposure scenarios when it is likely they can occur simultaneously based on the use pattern and the behavior associated with the exposed population, and when similar toxicological effects occur from different routes of exposure. HED reviewed all residential sources of exposure to determine which residential exposure scenarios would be appropriate to combine.

HED assessed both adult handler and post

- application exposure resulting from treatment of residential lawns; however, HED did not combine exposure resulting from adult handler and post

- application exposure because of the conservative assumptions and inputs within each

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## Page 33 of 54 estim ated exposure scenario. The likelihood that a homeowner would treat their lawn and then repeatedly re

- enter the treated site continuously for 30 days is minimal. Furthermore, it is unlikely that a homeowner would treat their lawn and then play golf on a course treated with the same pesticide on the same day. HED believes that combining co

- occurring exposures resulting from handler and post

- application exposure would result in an overestimate of adult exposure. Therefore, HED selected the most conservati ve combined adult residential scenario, handler exposure (backpack scenario for liquids with an ARI of 5.1) as the contributing source of adult residential exposure.

There is the potential for post

- application dermal and incidental oral ex posure for children 1 < 2 years resulting from use of sulfentrazone on turf. Since the toxicological effects from the dermal and oral routes of exposure are the same, a total residential exposure assessment was conducted for children. The incidental oral scenarios (i.e., hand

- to

- mouth, object

- to

- mouth, and soil ingestion) should be considered inter

- related and it is likely that they occur interspersed amongst each other across time. Combining all three of these scenarios with the dermal exposure scenario would be overly

- conservative because of the conservative nature of each individual assessment. Therefore, for the short

- term exposure duration, the post

- application exposure scenarios that were combined for children 1 to < 2 years old are the dermal and hand

- to

- mouth scenarios. This combination should be considered a protective estimate of children’s exposure to pesticides used on turf. For the intermediate

- term exposure duration, the only potential post

- application exposure scenario is soil ingestion. The total residential children’s short

- term post

- application exposure assessment results in an MOE greater than HED’s LOC (MOE = 320) and is not a risk of concern. The total residential children’s intermediate

- term post

- application exposure assessment al so results in an MOE greater than HED’s LOC (MOE = 1,100,000).

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## Page 34 of 54 Table 6.3. Short

- and Intermediate

- Term Residential Exposures for the Sulfentrazone Combined Residential Risk Calculations. 1

Population Handler Exposure

(mg/kg/day) 2 Dermal Inhalation
Aggregate Risk Index 5 Post

- application Exposure (mg/kg/day) 6 Residential
Post

application Total Exposure (mg/kg/day) 7 Residential

Post

application Total MOE 8 Dermal Inhalation MOE Risk Index 3 MOE Risk Index 4 Dermal Inhalation Oral

Short

- Term

Adult Male 0.095 0.0015 1,100 11 6,600 6.6 4.1 0.16 N/A N/A 0.16 610

Child 1 to < 2 years old N/A 0.27 N/A 0.0056 0.2756 320

Intermediate

- Term
Child 1 to < 2 years old N/A N/A N/A 1.2 x 10

- 5 1.2 x 10 - 5 1,100,000

1

. Bolded risk estimates should contribute to the residential exposure portion of the aggregate assessment. 2

. Handler exposure represents high

- end handler exposure, where the exposure duration is appropriate to assess. 3

. Dermal Risk Index = Dermal MOE / D ermal LOC. Dermal LOC = 100. 4

. Inhalation Risk Index = Inhalation MOE / Inhalation LOC. Inhalation LOC = 1000. 5

. ARI = 1 / ((1 ÷ Dermal Risk Index) + (1 ÷ (Inhalation Risk Index).
6

. Post

- application exposure represents high

- end dermal, inhalation and/ or incidental oral exposure for the relevant exposure duration.
7

. For adults, r esidential total exposure combines the highest dermal and inhalation exposures (Table 6.1), where applicable. For young chil dren, total residential exposure combines high

- end post application incidental oral AND dermal exposure, where applicable (Table 6.2). 8

. Total MOE = 1/ (1/Dermal MOE) + (1/Inhalation MOE) + (1/Incidental oral MOE). Dermal NOAEL = 100 mg/kg/day, Inhalation NOAEL = 10 mg/kg/day; Incidental oral NOAEL = 14 mg/kg /day.

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## Page 35 of 54 6.4 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. However, volatilization of pesticides may be a source of post

- application inhalation exposure to indi viduals nearby pesticide applications. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insect icide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The Agency is in the process of evaluat ing 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 devel oped, the Agency may revisit the need for a quantitative post

- application inhalation exposure assessment for sulfentrazone.

6.5 Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. This is particul arly the case with aerial application, but, to a lesser extent, could also be a potential source of exposure from the ground application method employed for sulfentrazone. The Agency has been working with the Spray Drift Task Force, EPA Regional Offices, and State Lead Agencies for pesticide regulation and other parties to develop the best spray

- drift

management practices (see the Agency’s Spray Drift website for more information at http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical

- by

- chemical basis, the Agency is now requiring interim mitigation measures for aerial applications that must be placed on product labels/labeling. The Agency has completed its evaluation of the new database submitted by the Spray Drift Task Force, a membersh ip of U.S. pesticide registrants, and is developing a policy on how to appropriately apply the data and the AgDRIFT ® 

## computer model to its risk assessments for pesticides applied by air, orchard airblast, and ground hydraulic methods. After the policy is in place, the Agency may impose further refinements in spray

- drift

management practices to reduce off

- target drift with specific products with significant risks associated with drift.

Although a quantitative residential post

- application inhalation exposur e assessment was not performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation exposure assessment was performed for flaggers. This exposure scenario is representative of a worse case inhalation (drift) exposure and may be considered protective of most outdoor agricultural and commercial post

- application inhalation exposure scenarios

.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide expo sures 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.

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## Page 36 of 54 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 5.4.3, above. All risk estimates are below the LOC.

7.2 Short

- and Inte rmediate

- 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 cur rently 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, dermal, and inhalation exposure risk assessments are appropriate to aggregate due to similarities in the toxicity endpoints observed between the oral and dermal routes. The sh ort

- and intermediate

term incidental oral, dermal, and inhalation 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 conducti ng 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 expose d to sulfentrazone through dermal, inhalation, and dietary (food and drinking water) routes. It was appropriate to aggregate handler dermal and inhalation exposures with dietary (food and water) exposures. The backpack scenario for mixing and loading dry flowables is the exposure scenario with the greatest risk estimate; therefore, the exposure estimates for this scenario are protective of other exposure scenarios. The LOC for oral exposures (MOEs <100) and inhalation exposures (MOEs <1000) are different , a total ARI approach was used for adults. ARIs of <1 are risk estimates of concern. 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 drinki ng water) exposures; therefore, it was appropriate to aggregate these exposures for the short

- term duration. For the intermediate

- term exposure duration, the only potential post

- application exposure scenario is soil ingestion; therefore, this

exposure was aggregated with dietary (food and drinking water) for the 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 prote ctive of other children population subgroups. The LOC is 100; therefore MOEs <100 are risk estimates of

concern.

Tables 7.2.1, 7.2.2, and 7.2.3 summarize the short

- and intermediate

- term aggregate exposures and risk estimates for 1

- 2 year olds and adults. The aggregate short

- and intermediate

- term ARIs are >1 for adults and the aggregate MOEs are >100 for children; therefore, aggregate exposures to sulfentrazone are not of concern to HED.

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## Page 37 of 54 Table 7.2.1. Short

- term Aggregate Risk Calculations for C hildren 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 MOE 2 Dermal Exposure (mg/kg/day) Dermal

MOE 3

Children 1

- 2 years old 100 0.005855 0.0056 1220 0.27 370 280

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) + (1/inhalation)].



### Table 7.2.2. Intermediate

- term Aggregate Risk Calculations for Children 1

- 2 Years Old.

Population LOC Background Dietary + Incidental Oral Exposures Aggregate MOE (food, water, and residential) 2 Chronic Food and Water Exposure (mg/kg/day) Incidental Oral Exposure (mg/kg/day) 1

Children 1

- 2 years old 100 0.005855 0.000012 2390

1 Short

- term Incidental Oral Exposure = soil ingestion.

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



### Table 7.2.3. Short

- Term Aggregate Risk Calculations for Adults. 1

Population Dietary Exposure 2 Dermal Residential Exposure 3 Inhalation Residential Exposure 4 Aggregate ARI (food, water, and residential) 5 Chronic Food and Water Exposure (mg/kg/day) MOE ARI Dermal Exposure (mg/kg/day) MOE ARI Inhalation Exposure (mg/kg/day) MOE ARI

General U.S. Population 0.002422 5780 58 0.095 1,100 11 0.0015 6600 6.6 3.9

Adult Male 0.001966 7120 71 0.095 1,100 11 0.0015 6600 6.6 3.9

1

. HED is not concerned when ARIs are >1. 2

. MOE dietary = [(short

- or intermediate

- term oral NOAEL = 14 mg/kg/day)/(chronic dietary exposure)]. ARI dietary = [(MOE dietary)/(LOC (100))]. 3

. MOE dermal = [(short

- or intermediate

- term dermal NOAEL = 100 mg/kg/day)/(high

- end dermal residential exposure)]. ARI dermal = [(MOE dermal)/(LOC (100))]. Exposure values from Table 6.3. 4

. MOE inhalation = [(short

- or intermediate

- term inhalation NOAEL = 10 mg/kg/day)/(high

- end inhalation residential exposure)]. ARI inhalation = [(MOE inhalation)/(LO C (1000))]. Exposure values from Table 6.3. 5

. ARI Aggregate = 1/[(1/ARI dietary) + (1/ARI oral) + (1/ARI dermal) + (1/ARI inhalation)].



## 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 wa ter and, therefore, the chronic aggregate risk assessment is equivalent to the chronic dietary risk assessment discussed in Section 5.4.4, above. All risk estimates are below HED’s LOC.

7.4 Cancer Aggregate Risk

An aggregate cancer risk assessment wa s not performed because sulfentrazone is not considered to be a carcinogen.

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## Page 38 of 54 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 assum ed 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 poli cy 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

9.1 Short

- /Intermediate

- Term Handler Risk

Based on the anticipated use patterns, current labeling, and types of equipment that can potentially be used, occupational handler exposure is expected from the proposed uses.

No chemical

- specific data were available to assess potential exposure to pesticide handlers. Sources of generic data, used as surrogate data in the absence of chemical

- specific data, include the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), the Agricultural Handler Exposure Task Force (AHETF), and the Agricultural Reentry Task Force (ARTF). Some of these data are proprietary, and subject to the data protection provisions of FIFRA.

Based on the activity use pattern, the duration of exposu re is expected to be short

- term (1 to 30 days). Intermediate

- term exposures are less likely; however, the short

- and intermediate

- term PODs are the same; therefore, short

- term estimated risk estimates are protective of intermediate

term exposures. Long

- t erm exposures (>6 months) are not anticipated based on the proposed use pattern, so a long

- term assessment was not conducted. The sulfentrazone product labels direct mixers, loaders, applicators, and other handlers to wear a long

- sleeved shirt and long pa nts, chemical

- resistant gloves, and shoes plus socks.

Table 9.1.1 presents the exposure/risk estimates for short

- and intermediate

- term dermal and inhalation exposures for liquid and DF formulation applications. The combined dermal and inhalation exposur e risk estimates are not of concern (i.e., ARIs >1) at baseline (i.e., single layer of clothing, no gloves, no respirator) for all scenarios, except the following, which require additional PPE beyond what is currently on the labels:

Mixing/loading DFs for chemigation and groundboom applications requires the addition of gloves and a PF5 respirator; Mixing/loading/applying liquids for soil

- directed applications with mechanically

pressurized handgun requires the addition of gloves and a PF5 respirator; and Mixing/loading DFs for aerial application requires the addition of gloves and a PF10 respirator.

Table 9.1.2 presents the exposure/risk estimates for short

- and intermediate

- term dermal and

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## Page 39 of 54 inhalation exposures for dry bulk fertilizer applications. The combined dermal and inhalation exposure risk estimates are not of concern (i.e., ARIs >1) for all scenarios, except the following:

Mixing/loading DFs for commercial impregnation of dry bulk fertilizers results in risk estimates of conce rn using surrogate closed mixing/loading exposure data and assuming 960 tons treated daily.

The estimate for amount of dry bulk fertilizer treated is based on use data submitted previously for another chemical and is the best data currently available to H ED. Chemical

- specific use data could be submitted to refine the assessment.

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## Page 40 of 54 Table 9.1.1. Short

- /Intermediate

- Term Occupational Exposure and Risk Estimates for Sulfentrazone.

Exposure Scenario Dermal Unit

Exposure (ug/lb ai) 1 Inhalation

Unit Exposure (ug/lb ai) 1 Application

Rate 2 Amount

Treated Daily 3 Dose (mg/kg/day) 4,5 MOE 6,7 Dermal Risk Index 8 Inhalation

Risk Index 9 ARI 10 Dermal Inhalation Dermal (LOC = 100) Inhalation

(LOC = 1000)

Mixer/Loader DFs

Aerial Application Baseline:

227

SL w/G: 51.6 Baseline:

8.96

PF5 R: 1.79

PF10 R: 0.9 0.375 lb

ai/A 1200 A Baseline: 1.5

SL w/G: 0.34 Baseline:

0.058

PF5: 0.012

PF10: 0.0059 Baseline:

68

SL w/G: 300 Baseline:

170

PF5: 860

PF10: 1,700 Baseline:

0.68

SL w/G : 3 Baseline:

0.17

PF5: 0.86

PF10: 1.7 Baseline: 0.14

SL w/G + No R: 0.16

SL w/G + PF5: 0.67

SL w/G + PF10: 1.1

Chemigation Applications Baseline:

227

SL w/G: 51.6 Baseline:

8.96

PF5 R: 1.79 0.375 lb

ai/A 350 A Baseline: 0.43

SL w/G: 0.098 Baseline:

0.017

PF5: 0.0034 Baseline:

230

SL w/G: 1,000 Baseline:

590

PF5: 2,900 Baseline:

2.3

SL w/G : 10 Baseline:

0.59

PF5: 2.9 Baseline: 0.47

SL w/G + No R: 0.56

SL w/G + PF5: 2.2

Groundboom Applications Baseline:

227

SL w/G: 51.6 Baseline:

8.96

PF5 R: 1.79 0.375 lb

ai/A 200 A Baseline: 0.25

SL w/G: 0.056 Baseline:

0.0097

PF5: 0.0019 Baseline:

410

SL w/G: 1,800 Baseline:

1,000

PF5: 5,100 Baseline:

4.1

SL w/G : 18 Baseline: 1

PF5: 5.1 Baseline: 0.8

SL w/G + No R: 0.95

SL w/G + PF5: 4 Mixer/Loader Liquids

Aerial Application Baseline:

220

SL w/G : 37.6 Baseline:

0.219 0.375 lb

ai/A 1200 A Baseline: 1.4

SL w/G : 0.25 Baseline:

0.0014 Baseline:

70

SL w/G : 410 Baseline:

7,000 Baseline:

0.7

SL w/G: 4.1 Baseline: 7 Baseline: 0.64

SL w/G + No R: 2.6 Chemigation Applications Baseline:

220 Baseline:

0.219 0.375 lb

ai/A 350 A Baseline: 0.42 Baseline:

0.00042 Baseline:

240 Baseline:

24,000 Baseline:

2.4 Baseline:

24 Baseline: 2.2

Groundboom Applications Baseline:

220 Baseline:

0.219 0.375 lb

ai/A 200 A Baseline: 0.24 Baseline:

0.00024 Baseline:

420 Baseline:

42,000 Baseline:

4.2 Baseline:

42 Baseline: 3.8

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## Page 41 of 54 Table 9.1.1. Short

- /Intermediate

- Term Occupational Exposure and Risk Estimates for Sulfentrazone.

Exposure Scenario Dermal Unit

Exposure (ug/lb ai) 1 Inhalation

Unit Exposure (ug/lb ai) 1 Application

Rate 2 Amount

Treated Daily 3 Dose (mg/kg/day) 4,5 MOE 6,7 Dermal Risk Index 8 Inhalation

Risk Index 9 ARI 10 Dermal Inhalation Dermal (LOC = 100) Inhalation

(LOC = 1000)
Applicator Applicator, Aerial, Fixed

Wing EC: 5 EC: 0.068 0.375 lb ai/A 1200 A EC: 0.033 EC: 0.00044 EC: 3,100 EC: 23,000 EC: 31 EC: 23 EC: 13

Applicator, Open Cab Groundboom Baseline:

78.6 Baseline:

0.34 0.375 lb

ai/A 200 A Baseline: 0.085 Baseline:

0.00037 Baseline:

1,200 Baseline:

27,000 Baseline:

12 Baseline:

27 Baseline: 8.3

Flagger

Flagger Baseline: 11 Baseline: 0.35 0.375 lb

ai/A 350 A Baseline: 0.021 Baseline:

0.00067 Baseline:

4,800 Baseline:

15,000 Baseline:

48 Baseline:

15 Baseline: 11

Mixer/Loader/Applicator

Mechanically

pressurized Handgun Sprayer

– Soil Directed Application Baseline:

4,310

SL w/G: 4,310 Baseline:

3,931

PF5: 786 0.375 lb

ai/A 1 A Baseline: 0.023

SL w/G: 0.023 Baseline:

0.021

PF5: 0.0043 Baseline:

4,300

SL w/G: 4,300 Baseline:

470

PF5: 2,300 Baseline:

43

SL w/G: 43 Baseline:

0.47

PF5: 2.3 Baseline:

0.46

SL w/G + No R: 0.46

SL w/G + PF5: 2.2

1

. Based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (September 26, 2011); includes data from PH ED/ORETF/AHETF (level of mitigation: Baseline and PPE (gloves)). Baseline = single layer and no gloves; no respirator; SL w/G = s ingle layer w/glove; PF5 R = PF5 Respirator; PF10 R = PF 10 Respirator; EC = Engineering control. 2

. Based on proposed labels for sulfentrazone (see Table 3.0.1 in Section 3.0). 3

. Exposure Science Advisory Council (ExpoSAC) Policy #9.1. 4

. Dermal Dose = D ermal Unit Exposure (ug/lb ai) x CF (0.001 mg/ug) x Application Rate (lb ai/acre) x 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 (ug/lb ai ) x CF (0.001 mg/ug) x Application Rate (lb ai/acre) x Area Treated (A/day) / BW (69 kg).
7

. Inhalation MOE = Inhalation NOAEL (10 mg/kg/day) / Inhalation Dose (mg/kg/day). 8

. Dermal Risk Index = Dermal MOE / Dermal LOC. Dermal LOC = 100. 9

. Inhalation Ri sk Index = Inhalation MOE / Inhalation LOC. Inhalation LOC = 1000. 10

. ARI = 1 / ((1 ÷ Dermal Risk Index) + (1 ÷ (Inhalation Risk Index)) . No R = no respirator.

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## Page 42 of 54 Table 9.1.2. Short

- /Intermediate

- Term Occupational Exposure and Risk Estimates for Dry Bulk Fertilizer Use of Sulfentrazone.

Exposure Scenario Dermal Unit Exposure (ug/lb ai) 1 Inhalation

Unit Exposure (ug/lb ai) 1 Applicati

on Rate 2 Amount

Treated Daily 3 Dose (mg/kg/day) 4,5 MOE 6,7

Dermal Risk Index 8 Inhalation

Risk Index 9 ARI 10 Dermal Inhalation Dermal (LOC = 100) Inhalation

(LOC = 1000) Mixer/Loader Dry Flowables

Commercial Impregnation of Dry Bulk Fertilizers 9.8

(closed system) 0.24

(closed system) 3.75 lb

ai/ton 960 tons 0.51 0.013 200 800 2 (closed system) 0.8 (closed

system) 0.57 (closed

system

On

- farm
I mpregnation of Dry Bulk Fertilizers Baseline: 227 Baseline:

8.96 0.375 lb

ai/A 160 A 0.20 0.0078 510 1,300 Baseline: 5.1 Baseline: 1.3 Baseline: 1

80 A 0.099 0.0039 1,000 2,600 Baseline: 10 Baseline: 2.6 Baseline: 2.1

Mixer/Loader Liquids

Commercial Impregnation of Dry Bulk Fertilizers 8.6

(closed system) 0.083

(closed system) 3.75 lb

ai/ton 960 tons 0.45 0.0043 220 2,300 2.2 (closed system) 2.3 (closed

system) 1.1 (closed

system

On

- farm
I mpregnation of Dry Bulk Fertilizers Baseline: 220 Baseline:

0.219 0.375 lb

ai/A 160 A 0.19 0.00019 520 53,000 Baseline: 5.2 Baseline: 53 Baseline: 4.7

80 A 0.096 0.000095 1,000 110,000 Baseline: 10 Baseline: 110 Baseline: 9.2

Applicator

Commercial Impregnation of Dry Bulk Fertilizers Baseline: 9.9 Baseline:

1.2 0.375 lb

ai/A 320 0.017 0.0021 5,800 4,800 Baseline: 58 Baseline: 4.8 Baseline: 4.4

160 0.0086 0.0010 12,000 9,600 Baseline: 120 Baseline: 9.6 Baseline: 8.9

On

- farm Impregnation of Dry Bulk Fertilizers 160 0.0086 0.0010 12,000 9,600 Baseline: 120 Baseline: 9.6 Baseline: 8.9

80 0.0043 0.00052 23,000 19,000 Baseline: 230 Baseline: 19 Baseline: 18

1

. Based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (September 26, 2011); includes data from PH ED/ORETF/AHETF. Closed mixing/loading assumed for commercial impregnation of dry bulk fertilizer. Open mixing/loading assumed fo r on

- farm impregnation of dry bulk fertilizer. Exposure values for granular application via open cab solid broadcast spreader used as surrogate for application of impregnated dry bulk fertilizer. 2

. Based on proposed labels for sulfentrazone (see Table 3. 0.1 in Section 3.0). 3

. (ExpoSAC) Policy #9.1 and industry information. 4

. Dermal Dose = Dermal Unit Exposure (ug/lb ai) x CF (0.001 mg/ug) x Application Rate (lb ai/acre or lb ai/ton) x Area Treated or Amount Handled (A/day or tons/day) / BW (69 kg). 5

. D ermal MOE = Dermal NOAEL (100 mg/kg/day)/Dermal Dose (mg/kg/day).
6

. Inhalation Dose = Inhalation Unit Exposure (ug/lb ai) x CF (0.001 mg/ug) x Application Rate (lb ai/acre or lb ai/ton) x Area Treated or Amount Handled (A/day or tons/day) /BW (69 kg). 7

. Inhalation MOE = Inhalation NOAEL (10 mg/kg/day)/ Inhalation Dose (mg/kg/day). 8

. Dermal Risk Index = Dermal MOE / Dermal LOC. Dermal LOC = 100. 9

. Inhalation Risk Index = Inhalation MOE / Inhalation LOC. Inhalation LOC = 1000. 10

. ARI = 1 / ((1 ÷ Dermal Risk Index) + (1 ÷ (Inhalation Risk Index) )

.

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## Page 43 of 54 9.2 Short

- /Intermediate

- Post

- application Risk

9.2.1 Dermal Post

- application Risk

Most of the proposed uses for sulfentrazone are soil

- directed preplant or preemergent uses where no crop foliage is present. Currently, HED has no transfer coefficients or other data to assess post

- application dermal exposures to soil by occupational workers. In general, such exposures are considered to be negligible. Therefore, for the proposed soil

- directed uses, post

- application

exposures an d risks to occupational workers were not assessed.

The proposed use on non

- grass animal feed crops, which includes alfalfa, does allow for applications in

- season between cuttings. The proposed labels recommend that applications are made as soon as poss ible after cuttings and up to 6 inches of re

- growth; therefore, a post

application assessment has been conducted for activities associated with early season alfalfa. Transfer coefficients of 1,100 and 1,900 cm 2 

## /hr for scouting and hand set irrigation, res pectively, along with default assumptions with respect to the fraction available for transfer and residue dissipation were used to estimate post

- application exposures.

A summary of the post

- application MOEs and respective reentry intervals is provided i n Table 9.2.2. The short

- and intermediate

- term post

- application assessments for alfalfa resulted in MOEs of 100 or greater on “day 0” (immediately after application) for all exposure activities and are not of concern.

Table 9.2.2. Summary of Short

- a nd Intermediate

- Term Occupational Post

- application Risk Estimates for

Sulfentrazone.

Crop/Site Transfer

Coefficient (cm 2 

### /hr) Application Rate

(lb ai/A) DFR on Day 0

(ug/cm 2 

### ) 1 

### Day 0 MOE 2 

### Day X at which MOE ≥ LOC
ST and IT ST and IT
Alfalfa 1,100 0.375 1.052 750 0

1,900 430 0

1

. DFR = AR x F x (1

- D)t x 4.54E8 μg/lb x 2.47E

- 8 acre/cm2.
2

. MOE = POD (NOAEL, 100 mg/kg/day) / Daily Dermal Dose. Daily Dermal Dose = [DFR (μg/cm 2 ) x TC x 0.001 mg/μg x 8 hrs/day] body weight (69 kg adult).



## Short

- and intermediate

- term post

- application risk estimates were not a concern on day 0 (12 hours following application) for all post

- application activities. Therefore, the REI is based on the acute toxicity of sulfentrazone. Typically, under the Worker Protection Standard (WPS) for agricultural pesticides, active ingredients classified as Acute III or IV for acute dermal, eye irritation and primary skin irrigation are assigned a 12

- hour REI. Therefore, the WPS interim REI of 12 hours is adequate to pro tect agricultural workers from post

- application exposures to sulfentrazone.

9.2.2 Inhalation Post

- application Risk

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

- application inhalation exposure assessment was not performed fo r sulfentrazone at this time. 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

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## Page 44 of 54 of pest icides 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. The Agency received the SAP’s final report on M arch 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report as well as available post

- application inhalation exposure data generated by the Agricultural Reentry Task Force and m ay, 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.

10.0 References

Occupational and Residential Exposure Memo: K. Lowe, 17

- MAY

- 2012, D389974; Residue Chemistry Memo: G. Kramer, 14

- JUN

- 2012; D 389972; Drinking Water Memo: M. Barrett, 03

- APR

- 2012; D39377 and D397770; Dietary Memo: J. Van Alstine, 14

- JUN

- 2012 ; D389973 ; 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.

cc: J. Van Alstine (RAB1), G. Kramer (RAB1), K. Lowe (RAB1), C. Rodriguez (RAB1) RDI: Branch (5/2/12); Dana Vogel (5/10/12) J. L. Van Alstine:S10951:PY

- S:(703)603

- 8866:7509P:RAB1

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## Page 45 of 54 Appendix A. Toxicology Profile

Table A.1. Acute Toxicity Profile

– Sulfentrazone.
Guideline
No. Study Type MRID(s) Results Toxicity Category
870.1100 Acute oral [rat] 41911605 LD 50 = 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.2. Toxicity Profile for Sulfentrazone
Guideline No./ Study Type MRID No. (year)/Classification/
Doses Results

870.3100 90

- Day oral toxicity (rat) 43004601 (1990) Acceptable/Guideline 0, 300, 1000, 3000, & 7000 ppm, M: 0, 3.3, 6.7, 19.9, 65.8, 199.3, & 534.9 mg/kg/day
F: 0, 4, 7.7, 23.1, 78.1, 230.5, & 404.3 mg/kg/day Systemic Toxicity NOAEL = 19.9 mg/kg/day in males and 23.1 mg/kg/day in females. Systemic Toxicity LOAEL = 65.8 mg/kg/day in males and 78.1 mg/kg/day in females, based on clinical signs of anemia (reduced hem atocrit, hemoglobin, mean cell volume, and mean cell hemoglobin values during treatment).
870.3100 90

- Day oral toxicity (mice) 43616517 (1993) Acceptable/Guideline 0, 50, 100, 300, 550, 1000, & 3000 ppm M: 0, 10.3, 17.8, 60, 108.4, & 194.4 mg/kg/day
F: 0, 13.9, 29, 79.8, 143.6, & 257 mg/kg/day Systemic Toxicity NOAEL = 60 mg/kg/day in males and 79.8 mg/kg/day in females. Systemic Toxicity LOAEL = 108.4 mg/kg/day in males and 143.6 mg/kg/day in females, based on decreased body weights, body

- weight gains, red blood cells, hemoglobin, hematocrit, and severity of splenic micropathology (increased incidence and severity of extramedullary hematopoiesis). Four

- week recovery period reversed all the treatment related effects except extramedullary hematopoiesis; h owever, 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 hemoglobin, hematocrit, mean cell volume, mean cell hemoglobin and mean cell hemoglobin concentration,

a nd increased absolute liver weights and alkaline phosphatase levels, and microscopic changes in the liver and spleen (pigmented sinusoidal microphages in the liver, swollen centrilobular hepatocytes and pigmented reticuloendothelial cells in the spleen).
870.3200 28

- Day dermal toxicity (rabbit) 44248301 (1996) Acceptable/Guideline 0, 10, 30, 100, 300, & 1000 mg/kg/day Systemic and Dermal Toxicity NOAEL = 1000 mg/kg/day (highest dose tested or HDT). Systemic and Dermal Toxicity LOAEL was not established.
870.3700a Prenatal Developmental (rat) 42932104 (1992) Acceptable/Guideline 0, 1, 10, 25, & 50 mg/kg/day Maternal NOAEL = 25 mg/kg/day. Maternal LOAEL = 50 mg/kg/day, based upon increased relative splenic extramedullary hematopoiesis. Developmental NOAEL = 10 mg/kg/day. Developmental LOAEL = 25 mg/kg/day, based upon decreased mean fetal weights, and retardation in skeletal

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## Page 46 of 54 Table A.2. Toxicity Profile for Sulfentrazone
Guideline No./ Study Type MRID No. (year)/Classification/
Doses Results

development evidenced by an increased number of litters with any variation and by decreased number of caudal vertebral and metacarpal os sification sites.
870.3700 Prenatal developmental (rat) 43651003 (1992) Acceptable/Non

- Guideline 0, 25, & 50 mg/kg/day Study was conducted to evaluate external and cardiac abnormalities. Maternal NOAEL = 25 mg/kg/day. Maternal LOAEL = 50 mg/kg/day, based on decreased mean body weights during gestation, and decreased litter size. Developmental NOAEL = 25 mg/kg/day. Developmental LOAEL = 50 mg/kg/day, based on significant reductions in the number of implantations and percentage of live fetuses, increase in t he percentage of early resorptions, and decreased fetal body weights.

Supplemental study to the 1992 Developmental

- Toxicity 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 LOA EL = 250 mg/kg/day, based on increased resorptions, decreased live fetuses per litter, and decreased fetal weights.
870.3800 2

- Generation reproduction and fertility effects (rat) 43345408 (1994) Acceptable/Guideline 0, 200, 500, & 700 ppm M/F: 0, 14/16, 33/40, & 46/56 mg/kg/day Parental Toxicity NOAEL =14 (M) and 16 (F) mg/kg/day. Parental Toxicity LOAEL = 33 (M) and 40 (F) mg/kg/day based on decreased maternal body weight/body

- weight gain during gestation in both generation (P & F 1 ) and reduced premating body

- weight gain in second

- generation (F 1 ) 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 F 1 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 red uced 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 1

- Generation reproduction and fertility effects (rat) 4 3869101(1995) Acceptable/Nonguideline 0, 50, 100, 200, & 500 ppm
F 0 M/F: 0, 3.9/4.1, 7.8/13.4, Systemic/Developmental Toxicity NOAEL = 20 (F) mg/kg/day. Systemic/Developmen tal Toxicity LOAEL = 51 (F) mg/kg/day, (F 1 females), based on decrease in pre

- mating

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## Page 47 of 54 Table A.2. Toxicity Profile for Sulfentrazone
Guideline No./ Study Type MRID No. (year)/Classification/
Doses Results

16/16, & 40/43 mg/kg/day
F 1 M/F: 0/0, 4.5/5.0, 9.2/10.1, 18/20, & 45/51 mg/kg/day body

- weight gain (10%). Offspring and Reproductive Toxicity NOAEL = 16 mg/kg/day (M/F) mg/kg/day. Offspring and Reproductive Toxicity LOAEL F 1 = 40 (M/F) mg/kg/day, based on reduced gestation day

- 20 fetal weights; decreased postnatal day 0, 4, and 7 pup weights; decreased pup survival; delayed vaginal patency; reduced epididymal, prostate, and testicular weights. Additional information supports the conclusions reached in the 2

- 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 hemoglobin and hematocrit by study termination.

No evidence of carcinogenicity.
870.4300 Combined chronic toxicity/carcinogenicity rodents (rat) 43345409 (1994) Acceptable/Guideline M: 0, 600, 1000, 2000, & 3000

ppm F: 0, 300, 600, 1000 & 2000

ppm M/F: 0/0, 24.3/20, 40/36.4, 82.8/67, & 123.5/124.7 mg/kg/day Systemic Toxicity NOAEL = 40 mg/kg/day for males and 36.4 mg/kg/day for females. Systemic Toxicity LOAEL = 82.8 mg/kg/day for males and 67 mg/kg/day for females, based on do se

- related decreased body weights (11 & 19%), body

- weight gains (13 & 26%), food consumption (13 & 19%), hemoglobin, hematocrit, mean cell volume, and mean cell hemoglobin. Increased nucleated red blood cells and reticulocytes in bone of females at 124.7 m g/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

respons es 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 w ere exposed to sulfentrazone technical (94.2%) in non

- activated 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). In a forward gene mutation assay , sulfentrazone at precipitating levels were equivocally positive in the absence of S9 activation. This response was not repeated at doses up to 1800 g/mL in the presence of S9 activation.

870.5395 43004605 (1992) The test was negative in mice administered single

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## Page 48 of 54 Table A.2. Toxicity Profile for Sulfentrazone
Guideline No./ Study Type MRID No. (year)/Classification/
Doses Results

Mammalian erythrocyte micronucleus test 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 ho urs post

- dosing. Cyclophosphamide at 30 mg/kg was used as positive control. 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, mal e 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 cond itions of this assay up to the estimated maximum tolerable dose (MTD).

870.6200 Acute Neurotoxicity Study 43345405 (1994) Acceptable/Guideline 0, 250, 750, & 2000 mg/kg Systemic Toxicity NOAEL = 250 mg/kg/day. Systemic Toxicity LOAEL = 750 mg/kg/day, base d upon increased incidence of clinical signs, FOB findings, and decreased motor activity which was reversed by day 14 post dose.

No evidence of neuropathology at any dose.
870.6200 Subchronic Neurotoxicity Study 43345405 (1994) Acceptable/Guideline 0, 500, 2500, or 5000 ppm (0/0, 30/37, 150/180, or 265/292 mg/kg/day [M/F]) NOAEL = 500 ppm (30/37 mg/kg/day). LOAEL = 2500 ppm (150/180 mg/kg/day) based on increased incidence of clinical signs (M&F), decreased BW, BWG, and FC (F), and increased motor activi ty at week 13 only (F).

No evidence of neuropathology at any dose.
870.7485 Metabolism and pharmacokinetics (rat) 43345410 (1994) Acceptable/Guideline Phenyl

- 14 C

- sulfentrazone (98% pure.) was administered to Sprague

- Dawley rats (5 animals/sex/dose) by gavage as a single dose at levels of 50 and 500 mg/kg, or as a single dose of 50 mg/kg following a 14

- day pretreatment with non

radioactive sulfentrazone (50 mg/kg/day). Sulfentrazone was readily absorbed and 84 to 104% of the administered dose was exc reted 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 administer ed dose. 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).

Published lite rature 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) d uring gestation. The results of this non

- guideline study were published in the open literature. Due to limitations in study conduct and reporting of the statistical analysis, the study is of limited value in risk assessment.

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## Page 49 of 54 Appendix B. Physical/Ch emical 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/cm 3


### Water solubility 4.0 x 10 2 

### μg/g Solvent solubility 18.6% w/w in acetonitrile Vapor pressure 8 x 10 - 10 

### mm Hg Dissociation constant, pK
a 

### 6.56 Octanol/water partition coefficient, Log(K OW 

### ) 1.49 at pH 5

UV/visible absorption spectrum Not available

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## Page 5 0 of 54 Appendix C. Summary of Residue Data

Table C.1. Summary of Residue Data from Turnip Crop Field Trials with Sulfentrazone.

Commodity Analyte Total App.
Rate (lb ai/A) 1 PHI

(days) Residue Levels (ppm sulfentrazone equivalents) 2

n Sample Min. Sample

Max. LAFT 3 HAFT 3 Median Mean Std. Dev. Turnip (proposed use = 0.25 lb ai/A application rate, 46

- to 60

- day PHI) Turnip tops Combined

Residues 0.200

- 0.206 46

- 60 5 <0.15 <0.46 0.15 0.34 0.15 0.20 0.08

0.249

- 0.298 46

- 60 5 <0.15 <0.44 0.15 0.31 0.15 0.20 0.07 Turnip

roots Combined

Residues 0.200

- 0.206 46

- 60 5 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A

0.249

- 0.298 46

- 60 5 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A

1 Total application rate includes application of both formulations (4 lb/gal SC and 75% WG formulation).

2 Except for sample min/max, values reflect per

- trial averages; n = no. of field trials. For calculation of median, mean, and standard deviation, the LOQ (0.05 ppm for all analytes) was used for any results reported as <LOQ. N/A = not applicable.

3 LAFT = lowest average field trial; HAFT = highest average field trial.



### Table C.2. Summary of Residue Data from Rhubarb Crop Field Trials with Sulfentrazone.

Commodity Analyte Total App.
Rate (lb ai/A) PHI

(days) Residue Levels (ppm sulfentrazone equivale nts) 1

n Sample Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std.
Dev. Rhubarb (proposed use = 0.25 lb ai/A application rate, Postemergence just prior to plants breaking dormancy)

Rhubarb petiole Combined

Residues 0.252

- 0.264 78

- 85 3 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A

1 Except for sample min/max, values reflect per

- trial averages; n = no. of field trials. For calculation of median, mean, and standard deviation, the LOQ (0.05 ppm for all analytes) was used for any results reported as <LOQ. N/A = not applicable.

2 LAFT = lowes t average field trial; HAFT = highest average field trial.

3 Residues of the metabolites were not determined in parent equivalents; based on the structures of the parent and metabolites, molecular

- weight

- conversion factors would be 0.96x for DMS and 1.04x for HMS, when values are >LOQ.



### Table C.3. Summary of Residue Data from Wheat Crop Field Trials with Sulfentrazone.

Commodity Analyte Total App. Rate (lb ai/A) PHI

(days) Residue Levels (ppm sulfentrazone equivalents) 1

n Sample Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std. Dev. Spring Wheat (proposed use = 0.188 ai/A application rate, 46

- to 60

- day PHI for forage, 120

- day PHI for grain)

Wheat forage Combined

Residues 0.186

- 0.192 41

- 60 3 <0.15 <0.30 0.15 0.26 0.15 0.19 0.06

Wheat hay Combined

Residues 0.186

- 0.192 87

- 95 3 <0.15 <0.16 0.15 0.16 0.15 0.15 0.003

Wheat grain Combined

Residues 0.186

- 0.192 98

- 140 3 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A

Wheat

straw Combined

Residues 0.186

- 0.192 98

- 140 3 <0.15 <0.54 0.15 0.50 0.15 0.27 0.20

1 Except for sample min/max, values reflect per

- trial averages; n = no. of field trials. For calculation of median, mean, and standard deviation, the LOQ (0.05 ppm for all analytes) was used for any results reported as <LOQ. N/A = not applicable.

2 LAFT = lowes t average field trial; HAFT = highest average field trial.



### Table C. 4. Summary of Residue Data from Tree Nuts Crop Field Trials with Sulfentrazone.

Commodity Formulation Total App.
Rate (lb ai/A) PHI

(days) Combined Residue Levels (ppm) 1

n Sample Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std. Dev. Tree Nuts (proposed use = 0.375 lb ai/A application rate, 3

- day PHI)

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## Page 51 of 54 Table C. 4. Summary of Residue Data from Tree Nuts Crop Field Trials with Sulfentrazone.

Commodity Formulation Total App.
Rate (lb ai/A) PHI

(days) Combined Residue Levels (ppm) 1

n Sample Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std. Dev.
Almond, hulls 2 lb ai/gal SE 0.375

- 0.384 7 2 <0.15 <0.15 0.15 0.15 0.15 0.15 NA

75% DF 0.375 7 1 <0.15 <0.15 0.15 0.15 0.15 0.15 NA 4 lb ai/gal FlC 0.376

- 0.377 6

- 7 2 <0.15 <0.15 0.15 0.15 0.15 0.15 NA
Almond,

nutmeat 2 lb ai/gal SE 0.375

- 0.384 7 2 <0.15 <0.15 0.15 0.15 0.15 0.15 NA

75% DF 0.375 7 1 <0.15 <0.15 0.15 0.15 0.15 0.15 NA 4 lb ai/gal FlC 0.377 6

- 7 2 <0.15 <0.15 0.15 0.15 0.15 0.15 NA
Pecan,

nutmeat 2 lb ai/gal SE 0.374

- 0.375 7 2 <0.15 <0.15 0.15 0.15 0.15 0.15 NA

75% DF 0.377

- 0.382 7

- 8 2 <0.15 <0.15 0.15 0.15 0.15 0.15 NA 4 lb ai/gal FlC 0.373 7 1 <0.15 <0.15 0.15 0.15 0.15 0.15 NA

1 Except for sample min/max, values reflect per

- trial averages; n = no. of field trials. For calculation of median, mean, and standard deviation, the LOQ (0.05 ppm for all analytes) was used for any results reported as <LOQ. N/A = not applicable. Residues of th e metabolites were not determined in parent equivalents.

2 LAFT = lowest

- average

- field

- trial; HAFT = highest

- average

- field

- trial.



### Table C.5. Summary of Residue Data from Citrus Crop Field Trials with Sulfentrazone.

Commodity Analyte Total App.
Rate (lb ai/A) PHI

(days) Residue Levels (ppm) 1

n Sample Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std. Dev.


### Citrus (proposed use = 0.375 lb ai/A application rate, 3

- day PHI) Orange, Fruit Combined 0.373

- 0.377 6

- 7 12 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A

Lemon, Fruit Combined 0.373

- 0.382 7

- 8 5 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A Grapefruit, Fruit Combined 0.373

- 0.377 7

- 8 6 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A

1 Except for sample min/max, values reflect per

- trial averages; n = no. of field trials. For calculation of median, mean, and standard deviation, the LOQ (0.05 ppm for all analytes) was used for any results reported as <LOQ. N/A = not applicable. Residues of the metabolites were not determined in parent equivalents.

2 LAFT = lowest

- average

- field

- trial; HAFT = highest

- average

- field

- trial.



### Table C.6. Summary of Residue Data from Berry and Small Fruit Crop Field Trials with Sulfentrazone.

Commodity Formulation Total App. Rate (lb ai/A) PHI

(days) Combined Residue Levels (ppm) 1

n Sample Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std. Dev. 

### Berry and Small Fruit (proposed use = 0.375 lb ai/A application rate, 3

- day PHI) Grape, Fruit 2 lb ai/gal SE 0.373

- 0.376 6

- 8 3 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A

75% DF 0.373

- 0.377 6

- 8 3 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A 4 lb ai/gal FlC 0.371

- 0.386 6

- 8 3 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A Strawberry, Berry 2 lb ai/gal SE 0.371

- 0.377 7 2 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A

75% DF 0.375 7 1 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A 4 lb ai/gal FlC 0.372 7 1 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A Blueberry, Berry 2 lb ai/gal SE 0.372

- 0.382 7 2 < 0.15 <0.15 0.15 0.15 0.15 0.15 N/A

75% DF 0.376 7 1 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A 4 lb ai/gal FlC 0.382 7 1 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A Blackberry, Berry 2 lb ai/gal SE 0.379 7 1 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A

75% DF 0.376 7 1 < 0.15 <0.15 0.15 0.15 0.15 0.15 N/A Raspberry, 75% DF 0.374 7 1 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A

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## Page 52 of 54 Table C.6. Summary of Residue Data from Berry and Small Fruit Crop Field Trials with Sulfentrazone.

Commodity Formulation Total App. Rate (lb ai/A) PHI

(days) Combined Residue Levels (ppm) 1

n Sample Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std. Dev.
Berry 4 lb ai/gal FlC 0.379 7 1 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A Elderberry, Berry 2 lb ai/gal SE 0.375 7 1 <0.15 0.1506 0.1503 0.1503 0.1503 0.1503 N/A

4 lb ai/gal FlC 0.374 7 1 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A
Kiwifruit, Fruit 2 lb ai/gal SE 0.378 7 1 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A

75% DF 0.377 7 1 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A 4 lb ai/gal FlC 0.391 7 1 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A

1 Except for sample min/max, values reflect per

- trial averages; n = no. of field trials. For calculation of median, mean, and standard deviation, the LOQ (0.05 ppm for all analytes) was used for any results reported as <LOQ. N/A = not applicable. Residues of the metabolites were not determined in parent equivalents.

2 LAFT = lowest

- average

- field

- trial; HAFT = highest

- average

- field

- trial.



### Table C.7. Summary of Residue Data from Clover and Alfalfa Crop Field Trials with Sulfentrazone.

Commodity Analyte Treatment Type Total

Rate (lb ai/A) PHI

(days) Residue Levels (ppm) 1

n Sample Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std. Dev.
Crop Group 18: Nongrass Animal Feeds (proposed use = 0.375 ai/A application rate, 21

- day PHI for forage/hay, 41

- day PHI for seed)

Clover Forage Total

Residues Single 0.375 21 3 3 <0.266 3.85 0.279 3.66 1.18 1.71 1.75

Clover Hay Total

Residues Single 0.375 21 3 3 <0.772 17.6 0.797 15.7 3.68 6.73 7.90

Clover Seed Total

Residues Single 0.366

- 0.375 41

- 124 5 <0.15 1.71 0.15 1.64 0.189 0.484 0.648

Alfalfa Forage Total

Residues Single 0.375 21

- 23 9 <0.199 1.30 0.200 1.24 0.315 0.502 0.344

Alfalfa Hay Total

Residues Single 0.375 21

- 23 9 <0.540 3.64 0.549 3.58 1.72 1.803 1.19

Alfalfa Seed Total

Residues Single 0.369

- 0.375 71

- 161 5 <0.15 <0.15 0.15 0.15 0.15 0.15 N/A

1 Except for sample min/max, values reflect per

- trial averages; n = no. of field trials. For calculation of median, mean, and standard deviation, the LOQ (0.05 ppm for all analytes) was used for any results reported as <LOQ. N/A = not applicable.

2 LAFT = lowest

- average

- field

- trial; HAFT = highest

- average

- field

- trial.

3 Does not include clover forage and hay samples from Trial 04. Residues from this trial were determined by the petitioner to be statistical outliers. These residues were 10x and 6x high er than the next highest residue of forage and hay, respectively, from other trials that used the same pattern of test substance use.

4 Does not include alfalfa forage and hay samples from Trial 17. Residues from this trial were determined by the petitio ner to be statistical outliers. These residues were 5x higher than the next highest residue of forage and hay from other trials that u sed the same pattern of test substance use.



## Sunflower subgroup 20B

No new sunflower subgroup 20B field trial data were submitted. An individual tolerance has been established for the combined residues of sulfentrazone and its metabolites HMS and DMS in/on sunflower seed at 0.20 ppm [40 CFR §180.498(a)(2)]. The previously submitted residue data for sunflower seed are adeq uate to support the proposed crop subgroup tolerance for the combined residues of sulfentrazone, DMS, and HMS of 0.20 ppm in/on sunflower, subgroup 20B.

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## Page 53 of 54 Vegetable Soybean (edamame)

From the Minutes of the 11/30/2011 ChemSAC Meeting:

“IR

- 4 has received a pesticide clearance request from the states of IL and WA for the use of herbicide sulfentrazone on vegetable soybean (edamame) to control perennial and annual broadleaf weeds and grasses. The proposed labeling is to apply sulfentrazone as a pre

emergence treatment. IR

- 4 Project is requesting that existing data for lima bean (succulent) and pea (succulent) be used for extrapolation for vegetable soybean (edamame), and thereby be used to set a sulfentrazone tolerance on vegetable soybean (edamame) at 0.15

ppm.

A tolerance for the combined residues of sulfentrazone and its two metabolites is established at 0.15 ppm for pea, succulent, and bean, lima, succulent (CFR 180.498). Cultural practices and weed problems in succulent lima bean production are similar enough to vegetable soybean (edamame) production, and IR

- 4 is proposing that label rates and use pattern for sulfentrazone in vegetable soybean (edamame) will be the same as in succulent lima bean. No residues above the lowest level of method validation (LLMV) of 0.05 ppm were observed for sulfentrazone and two metabolites in any of the succulent pea or lima bean samples.

It is reasonable to expect that residues of sulfentrazone in or on vegetable soybean (edamame) when applied as in succulent lima bea ns would not exceed the proposed tolerances of 0.15 ppm. Therefore, the ChemSAC approves the IR

- 4 proposal for establishment a tolerance of 0.15 ppm for the combined residues of sulfentrazone and its two metabolites in/on soybean, vegetable, succulent bas ed on the existing sulfentrazone tolerance for pea, succulent and lima bean, succulent.”

Cowpea, Succulent (Tennessee only)

As the use pattern for cowpea is the same as that for lima bean (0.188 lb ai/A, preemergence), HED concludes that existing data fo r lima bean (succulent) can be extrapolated to cowpea, and thereby be used to set a tolerance for the combined residues of sulfentrazone, DMS, and HMS on cowpea, succulent at 0.15 ppm.

Lima Bean , Succulent (TN only)

IR

- 4 has requested to amend the curren t tolerances in 40 CFR 180.498 in or on bean, lima, succulent at 0.15 ppm by removing the tolerance from the table in Section (a)(2) and adding the tolerance to Section (c) Tolerances with regional registrations. As all four residue trials submitted to su pport this tolerance were conducted in TN ( 

## D287102, 1/10/03, G. Kramer), a regional registration is appropriate.

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## Page 54 of 54 Appendix D. 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 PHED 1.1; the AHETF database; the Outdoor Residential Exposure T ask Force (ORETF) database; and the ARTF database, are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics requirements. For certain studies, that 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 http://www.epa.gov/pesticides/science/handler

- exposure

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

- app

- exposure

- data.html

.