Halosulfuron-Methyl

Human Health Risk Assessment DP No. D404095

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Date: March 25, 2013

SUBJECT: Halosulfuron-Methyl: Human Health Risk Assessment for Proposed New Uses 

on Artichoke and Caneberry ( Crop subgroup 13-07A)

PC Code: 128721 DP Barcode: D404095

Decision No.: 465913 Registration No.: 81880-15, 81880-18, 81880-2

Petition No.: 2E8050 Regulatory Action: Section 3 Registration

Risk Assessment Type: Single Chemical/Aggregate Case No.: NA

TXR No.: NA CAS No.: 100784-20-1

MRID No.: NA 40 CFR: 180.479

FROM: Sheila Healy, Risk Assessor

Meheret Negussie, Chemist

Nancy Tsaur, Chemist, ORE Assessor

Risk Assessment Branch 3

Health Effects Division (7509P)

THROUGH: Christine Olinger, Branch Chief

Risk Assessment Branch 3

Health Effects Division (7509P)

TO: Barbara Madden/Sidney Jackson (RM 05)

Risk Integration, Minor Use & Emergency Response Branch

Registration Division (7505P)
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1.0 Executive Summary........................................................................................................... 4

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

2.1 Data Deficiencies ............................................................................................................ 7

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

2.2.1 Enforcement Analytical Method ............................................................................... 7

2.2.2 International Harmonization..................................................................................... 7

2.2.3 Recommended Tolerances......................................................................................... 7

2.2.4 Revisions to Petitioned-For Tolerances.................................................................... 8

2.3 Label Recommendations................................................................................................ 8

3.0 Introduction........................................................................................................................ 8

3.1 Chemical Identity ........................................................................................................... 9

3.2 Physical/Chemical Characteristics ............................................................................... 9

3.3 Pesticide Use Pattern...................................................................................................... 9

3.4 Anticipated Exposure Pathways................................................................................. 10

3.5 Consideration of Environmental Justice.................................................................... 11

4.0 Hazard Characterization and Dose-Response Assessment.......................................... 11

4.1 Summary of Toxicological Effects.............................................................................. 11

4.2 Safety factor for Infants and Children (FQPA Safety Factor) ................................ 12

4.2.1 Completeness of the Toxicology Database.............................................................. 12

4.2.2 Evidence of Neurotoxicity........................................................................................ 13

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal........ 13

4.2.4 Residual Uncertainty in the Exposure Database ................................................... 13

4.3 Toxicity Endpoint and Point of Departure Selections.............................................. 14

5.0 Dietary Exposure and Risk Assessment......................................................................... 16

5.1 Residues of Concern Summary and Rationale.......................................................... 16

5.2 Food Residue Profile .................................................................................................... 16

5.3 Water Residue Profile.................................................................................................. 17

5.4 Dietary Risk Assessment.............................................................................................. 17

5.4.1 Description of Residue Data Used in Dietary Assessment.................................... 17

5.4.2 Percent Crop Treated Used in Dietary Assessment .............................................. 17

5.4.3 Acute Dietary Risk Assessment............................................................................... 18

5.4.4 Chronic Dietary Risk Assessment........................................................................... 18

5.4.5 Cancer Dietary Risk Assessment............................................................................. 18

5.4.6 Summary Table......................................................................................................... 18

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 20

6.1 Residential Handler Exposure .................................................................................... 20

6.2.1 Post-Application Exposure ...................................................................................... 21

6.3 Combined Exposure..................................................................................................... 21

6.4 Residential Bystander Postapplication Inhalation Exposure................................... 22

6.5 Spray Drift.................................................................................................................... 22

7.0 Aggregate Exposure/Risk Characterization.................................................................. 23

7.1 Acute Aggregate Risk................................................................................................... 23

7.2 Short-Term Aggregate Risk........................................................................................ 23

7.3 Intermediate-Term Aggregate Risk ........................................................................... 24

7.4 Chronic Aggregate Risk .............................................................................................. 24

7.5 Cancer Aggregate Risk ................................................................................................ 24
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8.0 Cumulative Exposure/Risk Characterization ............................................................... 24

9.0 Occupational Exposure/Risk Characterization ............................................................ 24

9.1 Short- and Intermediate-Term Handler Risk ........................................................... 24

9.2 Short- and Intermediate-Term Post-Application Risk............................................. 28

9.2.1 Dermal Postapplication Risk ................................................................................... 28

9.2.2 Inhalation Postapplication Risk .............................................................................. 28

10.0 References......................................................................................................................... 28

Appendix A. Toxicology Profile and Executive Summaries .................................................. 30

A.1 Toxicology Data Requirements................................................................................... 30

A.2 Toxicity Profiles............................................................................................................ 31

Appendix B. Physical/Chemical Properties............................................................................. 35

Appendix C. Review of Human Research................................................................................ 36

Appendix D. International Residue Limits.............................................................................. 37
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1.0 Executive Summary

On behalf of Canyon Group L.L.C., c/o Gowan Company, the Interregional Research Project No. 

4 (IR-4) of Rutgers University is proposing to add new uses of the active ingredient (ai), 

halosulfuron-methyl on caneberry (subgroup 13-07A) and artichoke. Halosulfuron-methyl is a 

sulfonylurea herbicide which inhibits the plant enzyme acetolacetate synthase and is used for 

pre- and post-emergent control of annual broadleaf weeds and nutsedges in several agricultural 

crops as well as residential turf grass and ornamentals. 

The most recent risk assessment for halosulfuron-methyl was conducted in 2012 for uses on 

Proso Millet and Crop Group 17, Grass, Forage, Fodder, and Hay (D396458, C. Walls, 

07/19/12). In accordance with the 2007 revised 40 CFR Part 158 Toxicology data requirements, 

an immunotoxicity study and a subchronic inhalation toxicity study are required for halosulfuron 

methyl. However, HED has waived the inhalation toxicity study data requirement at this time 

(TXR0054045). 

Pending submission of an analytical standard for the rearrangement ester (RRE) of halosulfuronmethyl, there are no additional toxicology or residue chemistry issues that would preclude 

granting unconditional registration for the requested uses of halosulfuron-methyl on caneberry

subgroup 13-07A and artichoke.

Proposed Use Profile

Halosulfuron-methyl is formulated as a water dispersible granule (WG) and applied as 

postemergence broadcast foliar sprays using ground equipment only for caneberries and 

artichokes. Application through any type of irrigation system is prohibited. Halosulfuronmethyl may be applied to artichoke at a maximum seasonal application rate of 2 oz/A (0.094 lb 

ai/A); the label does not specify maximum applications per season. For caneberry, halosulfuronmethyl may be applied twice per season at a maximum annual application rate of 2 oz/A (0.094

lb ai/A). The restricted entry interval (REI) is 12 hours. 

These new uses are proposed to be added to two end-use product (EP) labels: Sandea® Herbicide 

(EPA Reg. No. 81880-18) with 75% ai by weight and GWN-3061 Herbicide (EPA Reg. No. 

81880-2) with 75% ai by weight.

Exposure Profile

Based on application rate and label information, exposure to halosulfuron methyl is expected to 

occur for acute-, short- , intermediate-term exposures. Chronic exposure (other than dietary) is 

not expected for the proposed use patterns. The proposed agricultural uses on caneberry and 

artichoke would result in new dietary exposures in both food and drinking water. There are also 

existing residential uses that would result in non-occupational exposure from handler and postapplication activities. In occupational settings, exposure is also expected during handler 

activities for proposed uses. 

Toxicity/Hazard

Halosulfuron-methyl has low acute toxicity via the oral (Toxicity Category IV), dermal (Toxicity

Category III), and inhalation (Toxicity Category IV) routes. Halosulfuron-methyl is a non-
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irritant for skin and eyes (Toxicity Category IV) and is not a dermal sensitizer. With repeated 

dosing, halosulfuron-methyl produces non-specific effects, which are frequently characterized by

reduced body weight/body weight gain in the test animals. In the prenatal developmental 

toxicity study in rats, increases in resorptions, soft tissue (dilation of the lateral ventricles) and 

skeletal variations, and decreases in body weights were seen in the fetuses compared to clinical 

signs and decreases in body weights and food consumption in the maternal animals at a similar 

dose level. In the rabbit developmental toxicity study, increases in resorptions and postimplantation losses and decrease in mean litter size were seen in the presence of decreases in 

body weight and food consumption in maternal animals were observed. However, a clear No 

Observable Adverse Effect Level (NOAEL) for these effects was established in both rat and 

rabbit developmental toxicity studies. Halosulfuron-methyl did not produce reproductive effects. 

No neurotoxic effects were observed in the acute or subchronic neurotoxicity studies.

Halosulfuron-methyl is classified as “not likely to be carcinogenic to humans.” It is negative for 

mutagenicity in a battery of genotoxicity studies. 

The toxicology database is adequate, with the exception of the requirement for an 

immunotoxicity study. The requirement for a subchronic inhalation toxicity study has been 

waived. 

The toxicity endpoints and points of departure (POD) for risk assessment were selected for the 

following exposure scenarios: acute and chronic dietary, short- and intermediate-term incidental 

oral, dermal and inhalation. A summary of toxicity endpoints and points of departure is 

presented in Table 4.3.1. Because of a common effect (i.e., body weight gain changes) seen in 

the studies selected for the endpoints for all three routes of exposure, Margins of Exposure 

(MOEs) and exposures can be combined where appropriate. The level of concern (LOC) for 

residential and occupational exposures via dermal and inhalation routes is a MOE less than 100. 

The Food Quality Protection Act (FQPA) safety factor is 1X. 

Dietary Exposure (Food and Water) and Risk Estimates

The residue chemistry data and environmental fate data are adequate to assess human exposure. 

There was no indication of an adverse effect attributable to a single dose for the general U.S. 

population. However, an acute reference dose (aRfD) was established for females 13-49 years 

old. Conservative acute and chronic dietary exposure assessments were performed for 

halosulfuron-methyl using tolerance-level residues and 100% crop treated. The estimated 

drinking water concentration (EDWC) for rice was 59.2 μg/L and used directly in both the acute 

and chronic assessments. For all processed commodities, the Dietary Exposure Evaluation 

Model (DEEM) version 7.81 default processing factors were assumed. The results of the acute 

and chronic dietary (food and drinking water) analyses are below the Agency’s level of concern 

(LOC) for the general U.S. population and all population subgroups. The acute dietary (food and 

drinking water) exposure is estimated at <1% of the acute Population Adjusted Dose (aPAD) for 

the females 13-49 years old. The dietary (food and drinking water) exposure is estimated at 2%

of the chronic Population Adjusted Dose (cPAD) for the general U.S. population and 5.5 % of 

the cPAD for children 1-2 years old, the population subgroup with the highest estimated chronic 

dietary exposure to halosulfuron-methyl. Halosulfuron-methyl is classified as “not likely to be 

carcinogenic to humans;” therefore, cancer risk was not quantitatively assessed. 
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Residential Exposure and Risk Estimates

There are no proposed residential uses at this time; however, there are existing residential turf 

uses that have been reassessed to reflect updates to HED’s 2012 Residential SOPs along with 

policy changes for body weight assumptions. Short-term combined (dermal + inhalation) 

residential handler MOEs range from 7,200 to 190,000 and, therefore, are not of concern. Shortterm post-application MOEs for all residential scenarios range from 1,000 to 11,000,000 and, 

likewise, are not of concern.

Residential Aggregate Exposure Risk Estimates

There is potential for short-term aggregate exposure to halosulfuron methyl via the dietary

(which is considered background exposure) and residential (which is considered primary) 

pathways. All aggregate MOEs are greater than 100, which indicates that exposure and risk do 

not exceed HED’s LOC. The adult and children short-term aggregate (dietary + residential) 

MOEs are 1,800 and 840, respectively. Intermediate-term and chronic aggregate risk are 

expected to be equivalent to chronic exposure via the dietary pathway.

Occupational Exposure and Risk Estimates

Agricultural Handlers: There is potential for short- and intermediate-term occupational exposure 

to halosulfuron-methyl during handling activities (e.g. mixing, loading, application). All handler 

scenarios result in MOEs greater than the LOC (MOEs ≥ 100) at baseline or with recommended 

PPE. For artichoke, the baseline short-term combined (dermal + inhalation) MOEs range from 

650 to 14,000; for caneberry, MOEs range from 650 to 48,000. For artichoke, the baseline 

intermediate-term combined (dermal + inhalation) MOEs range from 88 to 1,800; for caneberry, 

MOEs range from 88 to 6,400. At baseline, the handheld equipment (mechanically-pressurized 

handgun) results in an MOE of 88 for both caneberry and artichoke. However, with 

recommended PPE of gloves, the MOE increases to 290.

Agricultural Post-application: There is no potential for dermal or inhalation short- and 

intermediate-term occupational exposure during post-application activities based on the proposed

use pattern for artichokes and caneberries. Based on the Agency's current practices, a 

quantitative non-cancer occupational post-application inhalation exposure assessment was not 

performed for halosulfuron-methyl at this time. If new policies or procedures are put into place, 

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

exposure assessment for halosulfuron-methyl.

Environmental Justice Considerations

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment. Dietary and non-dietary exposures were considered.

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 studies (listed in Appendix C) have 

been determined to require a review of their ethical conduct, and one of these studies is also 

subject to review by the Human Studies Review Board. All of the listed studies have received 

the appropriate review.
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2.0 HED Recommendations

Provided an analytical reference standard for the RRE of halosulfuron-methyl is submitted, HED

recommends granting an unconditional registration for the requested use of halosulfuron-methyl 

on artichoke and caneberry. Additional data are needed prior to the registration as outlined in 

Section 2.1 below. Tolerance recommendations are discussed in Section 2.2. There are no label 

modifications recommended for the proposed new uses. 

2.1 Data Deficiencies

860.1650 Submittal of Analytical Reference Standards

 An analytical reference standard for the rearrangement ester (RRE) of halosulfuronmethyl must be submitted to the EPA National Pesticide Standards Repository. 

875.2100 Submittal of Turf Transferable Residue (TTR)

 A TTR study is required for halosulfuron-methyl at this time since the dermal MOE for 

children 1 to <2 years old is less than 10 times the LOC of 100 (MOE = 960), based on 

default values for the fraction of application rate available for transfer after a turf 

application (DP404839, N. Tsaur, 02/21/2013).

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An adequate analytical method is available for enforcement of tolerances for halosulfuronmethyl residues in plants. The gas chromatography (GC) method quantifies halosulfuron-methyl 

as its rearrangement ester (RRE; 1-H-pyrazole-4-carboxylic acid, 3-chloro-5-[(4,6-dimethoxy-2-

pyrimidinyl)amino]-1-methyl, methyl ester) using thermionic-specific detection (TSD, nitrogen 

specific). Monsanto Analytical Method RES-109-97-4 (MRID 44495801) has been validated as 

an enforcement method by the Analytical Chemistry Branch (ACB)/Biological and Economic 

Analysis Division (BEAD). The limit of quantitation on rice straw, sugarcane, milo grain, field 

corn grain, cotton gin byproducts, and almond nutmeats was estimated to be 0.05 ppm 

(DP#250584, G. Jeffrey Herndon, 10/28/98). For confirmation, the RRE can be determined by 

GC/MS with monitoring at m/z 327.

Residues of halosulfuron-methyl and 3-CSA are not recoverable by the FDA Multiresidue 

Protocols.

2.2.2 International Harmonization

There are currently no Codex or Canadian maximum residue limits (MRLs) established for 

residues of halosulfuron-methyl in/on any commodity.

2.2.3 Recommended Tolerances
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HED has examined the residue chemistry database for halosulfuron-methyl. Pending submission 

of a reference standard for the RRE of halosulfuron-methyl (see requirements under Submittal of 

Analytical Reference Standards), there are no residue chemistry issues that would preclude 

granting a Section 3 registration for the requested uses on artichoke and caneberry, or the 

establishment of a tolerance for residues of the halosulfuron-methyl, methyl 3-chloro-5-[[[[(4,6-

dimethoxy-2-pyrimidinyl)amino]carbonyl]-amino]sulfonyl]-1-methyl-1H-pyrazole-4-

carboxylate, including its metabolites and degradates, in/on the commodities below. Compliance 

with the tolerance levels specified is to be determined by measuring only halosulfuron-methyl.

Table 2.2.3. Tolerance Summary for Halosulfuron-Methyl

Commodity

Established/Prop

osed Tolerance 

(ppm)

Recommended 

Tolerance (ppm)

Comments

Correct Commodity Definition

Artichoke 0.05 0.05

Caneberry subgroup 13-07A 0.05 0.05

2.2.4 Revisions to Petitioned-For Tolerances

There are no revisions to the tolerance petition (Table 2.2.3).

2.3 Label Recommendations

The labeled use pattern for caneberries must be clarified (for both products EPA Reg. No. 

81880-2 and EPA Reg. No. 81880-16). The proposed labels indicate that aerial application is 

just for corn, sorghum, and rice, but the specific use directions/limitations of caneberries do not 

explicitly state: “Do not apply by air.” This statement must be added on both labels in the 

caneberry section.

3.0 Introduction

Halosulfuron-methyl is a selective herbicide belonging to the sulfonylurea group of herbicides. 

It inhibits the action of the plant enzyme acetolactate synthase. The enzyme is not found in 

mammals (including humans). Halosulfuron-methyl is used for the pre- and postemergence 

control of annual broadleaf weeds and nutsedges in selected crops, residential turfgrass, and 

ornamentals. Permanent tolerances are established for a variety of field, fruit, vegetable crop, 

and livestock commodities under 40 CFR §180.479 at levels ranging from 0.01 to 20 ppm. 

Halosulfuron-methyl is sold in the US as dry flowable/water-dispersible granule formulations or 

as emulsifiable concentrates.

The petitioner, IR-4 on behalf of Canyon Group LLC (agent Gowan Company) has submitted a 

request for amended registration of two 75% WG formulations (Sandea Herbicide, EPA Reg. 

No. 81880-18, and GWN-3061, EPA Reg. No. 81880-2) for use on artichoke and caneberry. 

The proposed uses reflect ground application to caneberry at 0.024 - 0.094 lb ai/A or to artichoke 

at 0.047 - 0.094 lb ai/A. The proposed postharvest intervals (PHIs) are 15 days for caneberry

and 5 days for artichoke.
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3.1 Chemical Identity

Table 3.1. Test Compound Nomenclature.

Chemical structure

Common name Halosulfuron-methyl

Company experimental name MON 12000, NC-319

IUPAC name Methyl 3-chloro-5-(4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoyl)-1-

methylpyrazole-4-carboxylate

CAS name Methyl 3-chloro-5-[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]-1-

methyl-1H-pyrazole-4-carboxylate

CAS registry number 100784-20-1

End-use product (EP) 75% dry flowable SANDEA Herbicide; EPA Reg. No. 81880-18) and 75% WG 

(GWN-3061 Herbicide; EPA Reg. No. 81880-2)

Chemical structure of

3-chlorosulfonamide moiety 

(3-CSA)

3-Chloro-1-methyl-5-sulfamoyl-1H-pyrazole-4-carboxylic acid

3.2 Physical/Chemical Characteristics

An octanol/water partition coefficient of 1.67 at pH 5 and 23oC suggests that halosulfuronmethyl is not fat soluble. In fact, halosulfuron-methyl has significant water solubility especially 

at elevated pH. The low vapor pressure indicates little vaporization. Halosulfuron-methyl, like 

most other sulfonylurea herbicides, is extremely mobile with a median Koc of 104 g/mL and Kf 

(Freundlich partition) values ranging from 0.32 to 3.6 in four test soils. Its persistence in soil and 

water appears to be highly variable. Halosulfuron-methyl has the potential to leach to 

groundwater, and also presents concerns for transport to surface water by runoff. 

3.3 Pesticide Use Pattern

N

N

CH3

Cl

N

N N

H

N

H

O

S

O

O

O

CH3

O

CH3

O

O

CH3

N

N

CH3

Cl

NH2

S

O

O

OH

O
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Halosulfuron-methyl is a sulfonylurea herbicide proposed for pre- and post-emergence control of 

broadleaf weeds and nutsedge. The petitioner is proposing to add artichoke and caneberry

(subgroup 13-07A) to these two labels. The proposed use patterns are presented in Table 3.3.

Table 3.3. Summary of Directions for Use of Halosulfuron-Methyl.

Applic. Timing, 

Type, and Equip.

Applic. 

Rate 

(lb ai/A)

Max. No.

Applic. 

per

Season

Max. Annual

Applic. Rate

(lb ai/A)

PHI (day) Use Directions and Limitations

Caneberry subgroup 13-07A including: blackberry, loganberry, raspberry, black and red, wild raspberry, cultivars, 

varieties, and/or hybrids of these

Application to 

either side of crop 

row, Ground

0.5-1 oz 

(East of 

the 

Rockies)

0.75-2 oz 

(West of 

the 

Rockies) 

SANDEA 

or GWN3061

(0.024-

0.094)

2

2 oz

(0.094) 15

Apply a single or sequential application 

with an interval of 45 days (0.024-0.094 

lb ai/A) uniformly with ground 

equipment in a minimum of 15 gals of 

water per acre to the ground on either 

side of the row. Do not apply less than 

15 days before harvest. Do not apply if 

excessive weed growth prevents 

herbicide contact with ground. Use a 

non-ionic surfactant with postemergence applications.a

Artichoke

Application to 

either side of crop 

row, Ground only

1-2 oz 

SANDEA 

or GWN3061

(0.047-

0.094)

Not 

specified

2 oz

(0.094) 5

Apply at 0.047-0.094 lb ai/A uniformly 

with ground equipment in a minimum 

of 15 gals of water per acre to the 

ground on either side of the row and 

avoiding crop foliage. Do not apply less 

than 5 days before harvest. Do not 

apply by air. Use a non-ionic surfactant 

with post-emergence applications.

a Note to RD: The labeled use pattern for caneberries must be clarified (for both products EPA Reg. No. 81880-2 

and EPA Reg. No. 81880-16). The proposed labels indicate that aerial application is just for corn, sorghum, and 

rice, but the specific use directions/limitations of caneberries do not explicitly state: “Do not apply by air.” This 

statement should be added on both labels in the caneberry section.

3.4 Anticipated Exposure Pathways

The Registration Division has requested an assessment of human health risk to support the 

proposed new uses of halosulfuron-methyl on artichoke and caneberry (subgroup 13-07A). 

Humans may be exposed to halosulfuron-methyl in food and drinking water, since halosulfuronmethyl may be applied directly to growing crops and application may result in halosulfuronmethyl reaching surface and ground water sources of drinking water. Currently, there are 

residential uses of halosulfuron-methyl on turf, so there is likely to be exposure in residential 

settings. In an occupational setting, applicators may be exposed while handling the pesticide 

prior to application, as well as during application. There is a potential for post-application 

exposure for workers re-entering treated fields. There is also potential for residential postapplication exposure from turf use.
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Risk assessments have been previously conducted for halosulfuron-methyl, dated 07/19/12 

(D396458, C. Walls). This risk assessment considers all of the aforementioned exposure 

pathways based on the proposed new uses of halosulfuron-methyl, but also considers the existing 

uses as well, particularly for the dietary and residential exposure assessments. 

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

http://www.epa.gov/environmentaljustice/resources/policy/exec_order_12898.pdf. As a part of 

every pesticide risk assessment, OPP considers a large variety of consumer subgroups according 

to well-established procedures. In line with OPP policy, HED estimates risks to population 

subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water 

consumption, and activities in and around the home that involve pesticide use in a residential 

setting. Extensive data on food consumption patterns are compiled by the U.S. Department of 

Agriculture’s National Health and Nutrition Examination Survey, What We Eat in America, 

(NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a 

pesticide. These data are analyzed and categorized by subgroups based on age and ethnic group. 

Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and 

exposure assessments are performed when conditions or circumstances warrant. Whenever 

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

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

post-application are evaluated. Further considerations are currently in development as OPP has 

committed resources and expertise to the development of specialized software and models that 

consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary

patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

The most recent human health risk assessment was conducted for uses on proso millet and Crop 

Group 17 (C. Walls, 07/19/12, D396458). Since then, the requirement for a subchronic 

inhalation study has been waived (TXR 0054045). Additionally, an immunotoxicity waiver has 

been submitted and is under review. The hazard characterization and toxicity endpoints for risk 

assessment remain unchanged since the 2006 risk assessment for uses on alfalfa (M. Rust, 

9/21/2006, D331643). 

4.1 Summary of Toxicological Effects

Halosulfuron-methyl is a member of the sulfonylurea class of herbicides, and it inhibits

acetolactate synthase, a specific plant enzyme not found in mammals. The mode of action in 

mammals for halosulfuron-methyl is undetermined. 

The metabolism data indicated that with oral administration, halosulfuron-methyl was absorbed 

rapidly with incomplete absorption from the gastrointestinal tract. Within 72 hours, the absorbed 
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halosulfuron-methyl was eliminated in the urine and feces. Desmethyl NC-319 and the 5-

hydroxy derivative were the major urinary and fecal metabolites. No tissue retention was 

demonstrated. The absorption, elimination, and metabolism showed no sex dependence. 

Halosulfuron-methyl has low acute toxicity (Toxicity Category III-IV) by oral, dermal, and 

inhalation routes of exposure. It is not a dermal sensitizer. With repeated dosing, the available 

data show that the dog is the most sensitive mammalian species. In the dog, decreased body 

weight was seen in the chronic oral toxicity study and decreased body weight gain was observed 

in females in the subchronic oral toxicity study. In the rat and mouse, there was a decrease in 

body weight gains at high dose levels in short- and long-term oral and dermal studies. 

In the prenatal developmental toxicity study in rats, increases in resorptions, soft tissue (dilation 

of the lateral ventricles) and skeletal variations, and decreases in body weights were seen in the 

fetuses compared to clinical signs and decreases in body weights and food consumption in the 

maternal animals at similar dose level. In the rabbit developmental toxicity study, increases in 

resorptions and post-implantation losses and decrease in mean litter size was observed in the 

presence of decreases in body weight and food consumption in maternal animals. However, a 

clear NOAEL for these effects was established in both rat and rabbit developmental toxicity

studies. Halosulfuron-methyl did not produce reproductive effects. No neurotoxic effects were 

observed in the acute or subchronic neurotoxicity studies.

An estimated dermal absorption rate of 75% is based on results of an oral developmental toxicity

study and a 21-day dermal toxicity study in the same species (rat).

Halosulfuron-methyl is negative for mutagenicity in a battery of genotoxicity studies. It is 

classified as “not likely to be carcinogenic to humans” based on lack of evidence for 

carcinogenicity in mice and rats following long-term dietary administration. 

4.2 Safety factor for Infants and Children (FQPA Safety Factor)

The FQPA safety factor has been reduced to 1X for the reasons detailed below (4.2.1 - 4.2.4). 

4.2.1 Completeness of the Toxicology Database

The toxicology database for halosulfuron-methyl is complete with the exception of an 

immunotoxicity study . Current data requirements in 40 CFR §158 include an immunotoxicity

study (OPPTS Guideline 870.7800) for pesticide registration. A waiver request for this data 

requirement has been submitted and is under review. In the absence of specific immunotoxicity

studies, HED has evaluated the available toxicity database to determine whether an additional 

database uncertainty factor is needed to account for potential immunotoxicity. The toxicology

database of this chemical does not show any evidence of biologically relevant effects on the 

immune system. The overall weight of the evidence suggests that this chemical does not directly 

target the immune system. HED does not believe that immunotoxicity testing will result in a 

NOAEL less than that (10 mg/kg/day) used to derive the current cRfD of 0.1 mg/kg/day. 

Consequently, HED believes the existing data are sufficient for endpoint selection for 
Halosulfuron-Methyl

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exposure/risk assessment scenarios and for evaluation of the requirements under the FQPA, and 

an additional database uncertainty factor (UFDB) does not need to be applied at this time.

The requirement for a subchronic inhalation study has been waived (TXR 0054045).

4.2.2 Evidence of Neurotoxicity

Halosulfuron methyl is not an apparently neurotoxic chemical based on clinical observations of 

neurotoxicity during the conduct of developmental or chronic studies. No untoward 

neurobehavioral signs were observed at doses approaching the limit dose in any of the shortterm studies in rats or mice (subchronic oral, 21-day dermal) or chronic studies. No neurotoxic 

effects were observed during acute or subchronic neurotoxicity studies in which animals were 

dosed at systemically toxic dose levels. A developmental neurotoxicity study is not required at 

this time.

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

There was no quantitative evidence for increased susceptibility following pre- and/or post-natal 

exposure. However, there was qualitative evidence for increased susceptibility. In the rat study, 

increases in resorptions, soft tissue (dilation of the lateral ventricles) and skeletal variations, and 

decreases in body weights were seen in the fetuses compared to clinical signs and decreases in 

body weights and food consumption in the maternal animals. In the rabbit study, increases in 

resorptions and post-implantation losses and decrease in mean litter size were seen in the 

presence of decreases in body weight and food consumption in maternal animals. Thus, in both 

species, the developmental effect was considered to be qualitatively more severe than maternal 

effects (i.e., qualitative evidence for susceptibility). In both studies, there are clear 

NOAELs/LOAELs for developmental and maternal toxicities, developmental effects were seen 

in the presence of maternal toxicity, and the effects were only seen at the high dose. 

Additionally, in rats developmental effects were seen at a dose which is approaching the limitdose. The degree of concern is low and there are no residual uncertainties for prenatal toxicity in 

both rats and rabbits.

4.2.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the exposure database. Since the dietary and non-dietary

exposure estimates were based on several conservative assumptions, HED does not believe that 

the exposure estimates are underestimated. The dietary assessments conducted with DEEMFCID were conservative and utilized tolerance level residues for all crops, default processing 

factors for all commodities, and 100% crop treated was assumed for all commodities. The 

DEEM analysis also assumed that all drinking water will contain halosulfuron methyl at the 

highest EDWC levels modeled by the Environmental Fate and Effects Division (EFED) for 

ground water or surface water. For these reasons it can be concluded that the dietary analysis 

does not underestimate risk from exposure to halosulfuron methyl. Similarly, HED does not 

believe that the non-dietary occupational and residential exposures are underestimated because 

they are also based on conservative assumptions, including maximum application rates, labeled 
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personal protective equipment (PPE), and standard values for unit exposures and acreage 

treated/amount handled.

4.3 Toxicity Endpoint and Point of Departure Selections

There have been no changes to the prior dose-response assessment for halosulfuron methyl. The 

PODs and toxicity endpoints selected for various exposure scenarios applicable to this risk 

assessment are summarized in Tables 4.3.1 (Non-Occupational and Occupational). For the 

short- and intermediate-term inhalation exposure, the toxicity endpoints and points of departure 

were derived from the oral toxicity studies as indicated in the Table 4.3.1. 

Table 4.3.1 Summary of Toxicological Doses and Endpoints for Halosulfuron-methyl for Use in Dietary, 

Occupational and Non-Occupational Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

(Females 13-49 

years of age)

NOAEL= 

50

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x

Acute RfD = 0.5 

mg/kg/day

aPAD =0.5 

mg/kg/day

Developmental Toxicity - Rabbit

LOAEL = 150 mg/kg/day based on decreased 

mean litter size, increased number of 

resorptions (total and per dam) and increased 

postimplantation loss (developmental 

toxicity).

Acute Dietary 

(General 

Population 

including Infants 

and Children)

No adverse effect attributable to a single dose was identified; therefore, no dose/endpoint was 

selected for this exposure scenario.

Chronic 

Dietary (All 

Populations)

NOAEL= 

10 

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x

Chronic RfD = 

0.1

mg/kg/day

cPAD = 0.1 

mg/kg/day

Chronic Toxicity - Dog

LOAEL = 40 mg/kg/day based on decreased 

body weight gains in females.

Incidental Oral 

Short-Term (1-

30 days)

NOAEL= 

50 

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x

Residential LOC 

for MOE = 100

Developmental Toxicity - Rabbit

LOAEL = 150 mg/kg/day based on decreased

body weight gain, food consumption, and 

food efficiency (maternal toxicity).

Incidental Oral 

IntermediateTerm (1-6 

months)

NOAEL= 

10 

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x 

Residential LOC 

for MOE = 100

13 Week Subchronic Toxicity - Dog

LOAEL = 40 mg/kg/day based on decreased 

body weight gains and food efficiency along 

with hematological and clinical chemistry 

changes.

Dermal ShortTerm (1-30 

days)

NOAEL= 

100 

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x

Residential and 

Occupational 

LOC for MOE = 

100

21-Day Dermal Toxicity Study - Rat

LOAEL = 1000 mg/kg/day based on 

decreased body weight gain in males.
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Table 4.3.1 Summary of Toxicological Doses and Endpoints for Halosulfuron-methyl for Use in Dietary, 

Occupational and Non-Occupational Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Dermal 

IntermediateTerm (1-6 

months)+

NOAEL=10 

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x 

Residential and 

Occupational 

LOC for MOE = 

100

13 Week Subchronic Toxicity - Dog

LOAEL = 40 mg/kg/day based on decreased 

body weight gains and food efficiency along 

with hematological and clinical chemistry 

changes.

Inhalation 

Short- Term

(1-30 days)

NOAEL = 

50 

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x

Residential and 

Occupational 

LOC for MOE = 

100

Developmental Toxicity - Rabbit

LOAEL = 150 mg/kg/day based on decreased

body weight gain, food consumption, and 

food efficiency (maternal toxicity).

Inhalation 

IntermediateTerm (1-6 

months)

NOAEL= 

10 

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x 

Residential and 

Occupational 

LOC for MOE = 

100

13 Week Subchronic Toxicity - Dog

LOAEL = 40 mg/kg/day based on decreased 

body weight gains and food efficiency along 

with hematological and clinical chemistry 

changes.

Cancer (oral, 

dermal, 

inhalation)

Classification: "not likely to be carcinogenic to humans" by the oral route, based on no 

evidence of carcinogenicity from studies in rats and mice.

+

: A 75% dermal absorption factor should be used in route-to-route extrapolation for the intermediate term dermal 

exposure risk. Toxicity via the inhalation route is presumed to be equivalent to oral toxicity.

NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty 

factor. UFA = extrapolation from animal to human (inter-species). UFH = potential variation in sensitivity among 

members of the human population (intra-species). FQPA SF = FQPA Safety Factor. PAD = population adjusted 

dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = 

not applicable
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5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale

The nature of the residue in plants is adequately understood based on acceptable metabolism 

studies with corn, sugarcane, and soybean; all studies investigated pre- and postemergence uses. 

The metabolism of halosulfuron-methyl was similar in the three tested crops but dependent on 

the mode of application (pre- or postemergence). When halosulfuron-methyl was applied 

preemergence, initial breakdown of the herbicide in the soil and preferential uptake of the 

pyrazole moieties resulted in the primary residue being 3-CSA, which has been determined to be 

less toxic than the parent. With a postemergence application, the major residue was the parent 

compound with minimal translocation of the herbicide in the plant, except in grain where the 

major residue was 3-CSA. 

Based on the very low toxicity of the metabolite 3-CSA, relatively low toxicity of the parent 

compound, and low residue levels of both parent compound and the 3-CSA metabolite, HED 

previously concluded that the residue of concern in plants is the parent compound, halosulfuronmethyl.

HED has previously concluded that the residue of concern in ruminants is halosulfuron-methyl. 

However, because the approved enforcement method for livestock commodities quantifies the 

parent compound and metabolites containing the 3-CSA moiety by converting residues to 3-

CSA, tolerances for residues of parent and its metabolites in livestock commodities are 

determined as 3-CSA, expressed in halosulfuron-methyl equivalents. 

Halosulfuron methyl is the only residue included in the drinking water assessment.

Table 5.1. Summary of Metabolites and Degradates to be included in the Risk 

Assessment and Tolerance Expression

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Plants

Primary Crop Halosulfuron-methyl Halosulfuron-methyl

Rotational Crop Halosulfuron-methyl Halosulfuron-methyl

Livestock

Ruminant Halosulfuron-methyl* Halosulfuron-methyl, 3-CSA

Poultry Halosulfuron-methyl* Halosulfuron-methyl, 3-CSA

Drinking Water Halosulfuron-methyl Not Applicable

*Residues are determined as 3-CSA and expressed in halosulfuron-methyl equivalents.

5.2 Food Residue Profile

The submitted magnitude of the residue data, summarized in Table 2.2.3, are in accordance with 

OCSPP guidelines and adequate for risk assessment and tolerance assessment. For both crops, 

the number and locations of field trials are adequate. Both artichoke and caneberry trials reflect 

a single banded postemergence application (backpack) of a 75% ai formulation at a target 
Halosulfuron-Methyl

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application rate of ~0.093 lb ai/A. A non-ionic surfactant was used in both trials. The available 

data will support tolerances at the LOQ of 0.05 ppm for both artichoke and caneberry at 

respective preharvest intervals of 5 and 13-15 days. 

The field trial studies are supported by adequate storage stability data.

Adequate confined and limited field rotational crop data are available. HED previously

concluded that the residue of concern in rotational crops is halosulfuron-methyl. Based on the 

absence of the parent compound in the confined studies and in the limited field rotational crop 

studies, with the exception of one forage sample, HED previously concluded that rotational crop 

tolerances and restrictions are not required for halosulfuron-methyl.

5.3 Water Residue Profile

Estimated surface water and groundwater concentrations are shown in Table 5.3.1. 

The dietary exposure assessment used the value of 59.2 ppb for acute and chronic assessments. 

The drinking water assessment is based on Tier I surface water model simulation for the

halosulfuron-methyl use on rice since the resulting EWDCs are greater than those estimated for 

the proposed uses (D394244, J. Meléndez, 05/15/12; D404096, M. Barrett, 03/26/13). 

Table 5.3.1. Tier I Estimated Drinking Water Concentrations (EDWCs) for Human Health 

Drinking Water Risk Assessment

DRINKING WATER SOURCE

(MODEL USED) 

USE

(rate modeled)

MAXIMUM ESTIMATED DRINKING WATER 

CONCENTRATION (EDWC)c ( ppb)

Groundwater

(SCI-GROW)

Fallow ground

(0.125 lb a.i./A/season) a

Acute 0.065

Chronic <0.065

Surface Water

(Tier 1 Rice Model v.1.0)

Paddy Water/Tail Water; Rice

(0.0625 lb a.i./A/season) b

Acute 59.2

Chronic <59.2

a Covers all uses other than rice; for the corn, fallow ground, and sugarcane use patterns of halosulfuron-methyl, 

based on a seasonal application 0.125 lb a.i./A.

b Seasonal rate is 0.0625 lb a.i./A, which is half of the rate of fallow ground.

c Surface water concentrations calculated by the Tier I Rice Model v1.0 and ground water concentrations calculated 

by SCI-GROW do not distinguish between peak and chronic concentration.

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

Conservative acute and chronic dietary exposure assessments were conducted. Tolerance level 

residues were used for the existing and proposed uses in both the acute and chronic assessments. 

The EWDC value of 59.2 was used as the drinking water residue in both the acute and chronic 

assessments. Additionally, DEEM version 7.81 default processing factors were assumed in both 

assessments, as well.

5.4.2 Percent Crop Treated Used in Dietary Assessment

The acute and chronic dietary analyses assumed that 100% of the crop was treated (100% CT)
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5.4.3 Acute Dietary Risk Assessment

An acute dietary (food and drinking water) exposure and risk assessment was conducted using 

the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database 

(DEEM-FCID) Version 3.16. This software uses 2003-2008 food consumption data from the 

U.S. Department of Agriculture’s (USDA’s) National Health and Nutrition Examination Survey, 

What We Eat in America, (NHANES/WWEIA). A conservative dietary exposure assessment

was performed for halosulfuron methyl for the current uses and the proposed new uses on 

artichoke and caneberry (Subgroup 13-07A). The result of the acute dietary (food and drinking 

water) analysis is below the Agency’s LOC for females 13 -49 years old. For the general U.S. 

population, an appropriate dose/endpoint attributable to a single dose was not observed in the 

reviewed oral toxicity studies therefore, an acute dietary assessment was not conducted. The 

acute dietary exposure estimate at the 95th percentile is <1% of the acute population adjusted 

dose (aPAD) for females 13-49 years old, the only population subgroup of concern. The result 

of the acute dietary exposure analysis is reported in Table 5.4.6.

5.4.4 Chronic Dietary Risk Assessment

A chronic dietary (food and drinking water) exposure and risk assessment was conducted using 

DEEM-FCIDTM, Version 3.16. A conservative dietary exposure assessment was performed for 

halosulfuron methyl for the current uses, and proposed new uses on artichoke and caneberry

(Subgroup 13-07A). The results of the chronic dietary (food and drinking water) analysis are 

below the Agency’s level of concern for the general U.S. population and all population 

subgroups. The dietary (food and drinking water) exposure is estimated at 2% of the chronic 

Population Adjusted Dose (cPAD) for the general U.S. population and 5.5% of the cPAD for all 

children 1-2 years old, the most highly exposed population subgroup. The results of the chronic 

dietary exposure analyses are reported in Table 5.4.6.

5.4.5 Cancer Dietary Risk Assessment

Halosulfuron methyl is classified as “not likely to be carcinogenic to humans;” therefore, cancer 

risk was not assessed. 

5.4.6 Summary Table

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

Halosulfuron-Methyl

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary Cancer

Dietary 

Exposure 

(mg/kg/day)

% aPAD*

Dietary 

Exposure

(mg/kg/day)

% cPAD*

Dietary 

Exposure

(mg/kg/day)

Risk

General U.S. Population N/A N/A 0.002050 2.0 N/A N/A
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Table 5.4.6. Summary of Dietary (Food and Drinking Water) Exposure and Risk for 

Halosulfuron-Methyl

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary Cancer

Dietary 

Exposure 

(mg/kg/day)

% aPAD*

Dietary 

Exposure

(mg/kg/day)

% cPAD*

Dietary 

Exposure

(mg/kg/day)

Risk

All Infants (< 1 year old) 0.004871 4.9

Children 1-2 years old 0.005508 5.5

Children 3-5 years old 0.003884 3.9

Children 6-12 years old 0.002433 2.4

Youth 13-19 years old 0.001579 1.6

Adults 20-49 years old 0.001791 1.8

Adults 50+ years old 0.001737 1.7

Females 13-49 years old 0.003733 <1 0.001785 1.8

Values for the highest exposed population for each type of risk assessment are bolded
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6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no proposed residential uses with this petition; however, there are existing residential 

turf uses that have been reassessed in the most recent risk assessment (C. Walls, D396458,

07/19/12) to reflect updates to HED’s 2012 Residential SOPs along with policy changes for body

weight assumptions. The revision of residential exposures impacts the human health aggregate 

risk assessment for halosulfuron methyl.

6.1 Residential Handler Exposure

There are no proposed residential uses at this time. All of the existing residential uses have been 

previously reassessed to reflect updates to the HED 2012 Residential SOPs1along with policy

changes for body weight assumptions (N. Tsaur, DP394460, 06/12/12). There are no registered 

products that would lead to any residential handler or post-application risk estimates of concern. 

Summaries of the short-term combined (dermal + inhalation) risk estimates for residential 

handlers are included in Table 6.1. The maximum application rate for each exposure scenario is 

presented as the worst case scenario. All risk estimates are greater than the LOC of 100 and 

therefore not of concern (MOEs range from 7,200 to 190,000).

Table 6.1. Short-Term Residential Handler Exposure and Risk Estimates for Water Dispersible Granule 

Application of Halosulfuron-Methyl on Residential Turf.

Exposure 

Scenario

Application 

Rate a

Area 

Treated 

Daily b

Baseline Unit 

Exposure b Baseline Dose d

Baseline MOE e

Total 

MOE f Dermal Inhalation Dermal Inhalation

lb ai/A Acres mg/lb ai mg/kg/day Dermal Inhalation

ManuallyPressurized 

Handwand

0.14 0.115 69 1.1 0.0135 0.000215 7,400 230,000 7,200

Hose-End 

Sprayer

0.14 0.50 13.4 0.022 0.0114 0.0000187 8,800 2,700,000 8,800

Backpack

Sprayer 0.14 0.115 69 1.1 0.0135 0.000215 7,400 230,000 7,200

Sprinkler 

Can

0.14 0.023 13.4 0.022 0.000523 0.000000859 190,000 58,000,000 190,000

a Application Rates based on maximum application rates of registered residential turf uses for halosulfuron-methyl.

b Based on HED’s SOPs: Lawns/Turf (January 2012). 0.115A = 5 gallons × (label rate: 1000 ft2/1 gallon). 0.023 A = 1000 ft2.

c Baseline Dermal: no gloves, short pants. Inhalation: no respirator. 

d Dose (mg/kg/day) = daily unit exposure (mg/lb ai) x application rate (lb ai/A) × area treated (Acres/day) × absorption factor 

(%) ÷ body weight (80 kg). Dermal absorption factor = 100%. No inhalation absorption factor.

e MOE = NOAEL ÷ daily dose (mg/kg/day). ST Dermal NOAEL = 100 mg/kg/day. ST Inhalation NOAEL = 50 mg/kg/day. 

f Total MOE = 1/ [(1/Dermal MOE) + (1/Inhalation MOE)]. Level of concern = 100.

 

1 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
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6.2.1 Post-Application Exposure

Adults and children performing physical post-application activities on turf (e.g. golfing, mowing)

may receive dermal exposure to halosulfuron-methyl residues. Young children 1 to <2 years old 

may also receive incidental oral post-application exposure to halosulfuron-methyl from treated 

turf. The scenarios, routes of exposure, and lifestages previously assessed include: Physical 

activities on turf, adults (dermal) and children 1 to < 2 years old (dermal and incidental oral);

Mowing, adults (dermal) and children 11 to < 16 years old (dermal); and Golfing, adults

(dermal), children 11 to < 16 years old (dermal), and children 6 to < 11 years old (dermal). Postapplication risk estimates for all residential scenarios are greater than the LOC of 100 and 

therefore not of concern (MOEs range from 960 to 11,000,000). 

6.3 Combined Exposure

HED combines risk estimates resulting from separate post-application exposure scenarios when 

it is likely they can occur on the same day based on the use pattern and the behavior associated 

with the exposed population and when the toxicological effects are similar. For halosulfuronmethyl, the toxicological effects are similar for the dermal, inhalation, and incidental oral routes; 

therefore, the exposures via these routes were combined where appropriate. For residential 

handlers, dermal and inhalation exposures were combined. For post-application scenarios, 

dermal and incidental oral exposures were combined for children 1 to < 2 years old.

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 overlyconservative because of the conservative nature of each individual assessment. Therefore, 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.

All combined (dermal + inhalation) post-application scenarios resulted in MOEs greater than 100 

and were not of concern. Handler dermal exposure is not combined with post-application dermal 

exposure because a homeowner is unlikely to be conducting post-application activities on the 

same day in which they apply the chemical. Table 6.3 shows the combined residential risk 

estimates for adults and children.

Table 6.3. Short-Term Residential Exposures for the Halosulfuron-Methyl Combined Risk Estimates

Population

Handler MOEs 1 Residential 

Handler Total 

MOE 3

Post-Application MOEs 2 Residential PostApplication Total 

MOE Dermal Inhalation Dermal Inhalation Oral 4

Adult 7,400 230,000 7,200 1,900

N/A N/A

1,900

Child 11 to < 16 years old

N/A

21,000 21,000

Child 6 to < 11 years old 18,000 18,000

Child 1 to < 2 years old 960 23,000 920

1 Handler MOE represents high-end handler exposure, where the exposure duration is appropriate to assess.

2 Post-application MOE represents high-end incidental oral exposure for the relevant exposure duration.
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3 Total MOE = 1 ÷ [(1/Dermal MOE) + (1/Inhalation MOE)]. Dermal NOAEL = 100 mg/kg/day. Inhalation NOAEL = 50 

mg/kg/day.

4 Total MOE = 1÷ [(1/Dermal MOE) + (1/Incidental Oral MOE)]. Dermal NOAEL = 100 mg/kg/day. Incidental Oral NOAEL = 

50 mg/kg/day.

6.4 Residential Bystander Postapplication Inhalation Exposure

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

assessment was not performed for halosulfuron-methyl at this time primarily because the 

chemical is only formulated as a WG, has low acute inhalation toxicity (Toxicity Category IV), 

has low vapor pressure (<1 x 10-7 mm Hg at 25 oC), and has a low proposed use rate (0.094 lb 

ai/A). However, volatilization of pesticides may be a source of post-application inhalation 

exposure to individuals nearby pesticide applications. The Agency sought expert advice and 

input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and 

Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s 

final report on March 2, 20102. The Agency is in the process of evaluating the SAP report and 

may, as appropriate, develop policies and procedures to identify the need for and, subsequently, 

the way to incorporate post-application inhalation exposure into the Agency's risk assessments. 

If new policies or procedures are developed, the Agency may revisit the need for a quantitative 

post-application inhalation exposure assessment for halosulfuron-methyl.

6.5 Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but, to a lesser extent, could also be a 

potential source of exposure from the ground application method employed for halosulfuronmethyl. 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 information3. The 

Agency has completed its evaluation of the new database submitted by the Spray Drift Task 

Force, a membership of U.S. pesticide registrants, and is developing a policy on how to 

appropriately apply the data and the AgDRIFT computer model to its risk assessments for 

pesticides applied by air, orchard airblast, and ground hydraulic methods. After the policy is in 

place, the Agency may impose further refinements in spray drift management practices to reduce 

off-target drift with specific products with significant risk estimates associated with drift.

Although a quantitative residential post-application inhalation exposure 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 

worst case inhalation (drift) exposure and may be considered protective of most outdoor 

agricultural and commercial post-application inhalation exposure scenarios. 

It is noted that the 0.14 lb ai/acre application rate for turf was modeled to estimate postapplication residential exposure of children. As this rate is equal to or higher than many of 

 

2 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

3 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
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agricultural application rates, this scenario is protective of any exposure of farm children via 

spray drift from agricultural halosulfuron-methyl applications.

7.0 Aggregate Exposure/Risk Characterization

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

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

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

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

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

duration of exposure. For halosulfuron-methyl, potential exposures from food, drinking water, 

and residential scenarios were aggregated.

7.1 Acute Aggregate Risk

Refer to Section 5.4.3 which discusses acute dietary (food and drinking water) exposure in detail. 

The dietary route alone is relevant for acute exposure and risk assessment; the acute dietary

exposure and risk assessment conducted for halosulfuron-methyl is screening-level, wherein the 

assessment assigns tolerance level residue values to all food commodities proposed to be treated 

with halosulfuron-methyl and modeled residue values to all drinking water. No aggregate risk 

concerns were identified.

7.2 Short-Term Aggregate Risk

There is potential short-term exposure to halosulfuron-methyl via the dietary (which is 

considered background exposure) and residential (which is considered primary) pathways. For 

adults, these pathways lead to exposure via the oral (background) and dermal (post-application 

primary) routes. For children, these pathways lead to exposure via the oral (background), and 

incidental oral and dermal (primary) routes. MOEs are greater than 100, which indicates that 

exposure and risk do not exceed HED’s level of concern. 

The recommended residential exposure for use in the aggregate assessment of adults and 

children 1 to <2 years old reflects the combined post-application dermal plus hand-to-mouth 

exposures from turf treated with liquid applications. The adult and children short-term aggregate 

dietary and residential MOEs are 1,800 and 840, respectively.

Table 7.2. Short-Term Aggregate Risk Calculations

Population

Short-Term Scenario

LOC for 

Aggregate 

Risk1

Dietary 

MOE2

MOE Oral 

Residential 

Exposure3

MOE 

Dermal 

Residential 

Exposure4

Aggregate 

MOE (food, 

water, and 

residential)5

Adult 100 28,000 NA 1,900 1,800

Child 1 to < 2 years old 100 9,100 23,000 960 840

1 LOC = 100 (based on inter- and intra- species uncertainty factors totaling 100X).

2 MOE dietary = [(short-term oral NOAEL 50 mg/kg/day)/(chronic dietary exposure)]. See Tables 4.3.1 and 5.4.6

3 MOE oral = [(short-term oral NOAEL)/(hand-to-mouth residential exposure)]. See Table 6.3
Halosulfuron-Methyl

Human Health Risk Assessment DP No. D404095

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4 MOE dermal = [(short-term dermal NOAEL)/(high end dermal residential exposure)]. See Table 6.3

5 MOE Aggregate = 1/[(1/MOE dietary) + (1/MOE oral) + (1/MOE dermal)] 

7.3 Intermediate-Term Aggregate Risk

Intermediate-term exposure is not expected for the adult or child residential exposure pathway. 

Therefore, the intermediate-term aggregate risk would be equivalent to the chronic dietary

exposure estimate. Refer to Section 5.4.4.

7.4 Chronic Aggregate Risk

Chronic exposure is not expected for the adult residential (dermal and inhalation) exposure 

pathway. Therefore, the chronic aggregate risk would be equivalent to the chronic dietary

exposure estimate. Refer to Section 5.4.4.

7.5 Cancer Aggregate Risk

Halosulfuron methyl is classified as “not likely to be carcinogenic to humans;” therefore, an 

aggregate cancer assessment was not conducted.

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 halosulfuron methyl and any other substances and halosulfuron methyl does not appear to 

produce a toxic metabolite produced by other substances. For the purposes of this tolerance 

action, therefore, EPA has not assumed that halosulfuron methyl has a common mechanism of 

toxicity with other substances. For information regarding EPA’s efforts to determine which 

chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such 

chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning 

common mechanism determinations and procedures for cumulating effects from substances 

found to have a common mechanism on EPA’s website at 

http://www.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Characterization

9.1 Short- and Intermediate-Term Handler Risk

For caneberries and artichokes, halosulfuron-methyl is proposed to be applied up to two times 

per season, pre- and post-emergent to weed growth at a maximum application rate of 2 oz/A

(0.094 lb ai/A). The maximum handheld rate is proposed at 0.0094 lb ai/gal (based on a 

minimum of 10 gallons of water per acre). Handlers may apply either of the EPs as a foliar spray 

using only ground equipment for caneberries and artichokes. Since chemigation was both 

permitted and prohibited on the labels, it was assessed to be protective.
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Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational handler exposure is expected from the proposed uses. 

The quantitative exposure/risk assessment developed for occupational handlers is based on the 

following scenarios: mixing/loading dry flowables to support groundboom and chemigation 

applications; applying sprays with groundboom equipment; and mixing/loading/applying sprays 

for ground-directed application via mechanically-pressurized handguns.

All handler scenarios result in MOEs greater than the LOC (MOEs ≥ 100) at baseline or with 

recommended PPE, and are not of concern to HED. At baseline, short-term combined (dermal + 

inhalation) MOEs range from 650 to 48,000. With the exception of handheld equipment, 

baseline intermediate-term combined (dermal + inhalation) MOEs range from 120 to 6,400. At 

baseline, the handheld equipment (mechanically-pressurized handgun) results in an MOE of 88. 

However, with required PPE of gloves, the MOE is 290. Tables 9.1.1 and 9.1.2 summarize the 

risk estimates for the proposed uses.
Halosulfuron-Methyl

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Table 9.1.1. Short-Term Occupational Handler Non-Cancer Exposure and Risk Estimates for Halosulfuron-Methyl at Baseline

Exposure Scenario Crop or 

Target

Dermal Unit 

Exposurea

Inhalation Unit 

Exposurea Maximum 

Application 

Rateb

Area 

Treated or 

Amount 

Handled 

Dailyc

Dermal Inhalation Total

Dosed

MOEe

Dosef

MOEg MOEh

μg/lb ai mg/kg/day mg/kg/day

Mixer/Loader at Baseline

Mixing/Loading Dry Flowables 

for Groundboom Application

Caneberries,

Artichokes

227 8.96 0.094

lb ai/A

80

acres

0.0213 4,700 0.000840 60,000 4,400

Mixing/Loading Dry Flowables 

for Chemigation Application

Caneberries,

Artichokes

350

acres

0.0931 1,100 0.00368 14,000 1,000

Applicator at Baseline

Applying Sprays via 

Groundboom

Caneberries,

Artichokes 78.6 0.34 0.094

lb ai/A

80

acres

0.00738 14,000 0.0000319 1,600,000 14,000

Mixer/Loader/Applicator at Baseline

M/L/A for Ground-Directed 

Application via MechanicallyPressurized Handgun

Caneberries,

Artichokes 1300 3.9 0.0094lb ai/gal

1000

gallons 0.153 650 0.000458 110,000 650

a Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2012). Level of mitigation: baseline.

b Based on registered or proposed label (Reg. No. 81880-2).

c Exposure Science Advisory Council Policy #9.1.

d Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW (80 kg).

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

f Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW (80 kg).

g Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). ST Inhalation NOAEL = 50 mg/kg/day. LOC = 100.

h Total MOE = 1 ÷ (1/Dermal MOE + 1/Inhalation MOE).
Halosulfuron-Methyl

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Table 9.1.2. Intermediate-Term Occupational Handler Non-Cancer Exposure and Risk Estimates for Halosulfuron-Methyl

Exposure Scenario Crop or 

Target

Dermal Unit 

Exposurea

Inhalation Unit 

Exposurea Maximum 

Application 

Rateb

Area 

Treated or 

Amount 

Handled 

Dailyc

Dermal Inhalation Total

Dosed

MOEe

Dosef

MOEg MOEh

μg/lb ai mg/kg/day mg/kg/day

Mixer/Loader at Baseline

Mixing/Loading Dry Flowables 

for Groundboom Application

Caneberries,

Artichokes

227 8.96 0.094

lb ai/A

80

acres

0.0159 630 0.000840 12,000 600

Mixing/Loading Dry Flowables 

for Chemigation Application

Caneberries,

Artichokes

350

acres

0.0698 140 0.00368 2,700 130

Applicator at Baseline

Applying Sprays via 

Groundboom

Caneberries,

Artichokes 78.6 0.34 0.094

lb ai/A

80

acres

0.00553 1,800 0.0000319 310,000 1,800

Mixer/Loader/Applicator at Baseline

M/L/A for Ground-Directed 

Application via MechanicallyPressurized Handgun

Caneberries,

Artichokes 1300 3.9 0.0094lb ai/gal

1000

gallons 0.114 88 0.000458 22,000 88

Mixer/Loader/Applicator with Recommended PPE (Single Layer + Gloves)

M/L/A for Ground-Directed 

Application via MechanicallyPressurized Handgun

Caneberries,

Artichokes 390 3.9 0.0094lb ai/gal

1000

gallons 0.0343 290 0.000458 22,000 290

a Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2012). Level of mitigation: baseline.

b Based on registered or proposed label (Reg. No. 81880-2).

c Exposure Science Advisory Council Policy #9.1.

d Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) × DAF (75%) ÷ BW (80 

kg).

e Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). IT Dermal NOAEL = 10 mg/kg/day. LOC = 100.

f Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW (80 kg).

g Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). IT Inhalation NOAEL = 10 mg/kg/day. LOC = 100.

h Total MOE = NOAEL (mg/kg/day) ÷ Dermal Dose + Inhalation Dose.
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9.2 Short- and Intermediate-Term Post-Application Risk

9.2.1 Dermal Postapplication Risk

Dermal post-application exposure is not expected from caneberries or artichokes treated with 

halosulfuron-methyl because the label indicates that contact with the planted crop should be 

avoided.

The REI specified on the proposed label is based on the acute toxicity of halosulfuron-methyl. 

Halosulfuron-methyl is classified as Toxicity Category III via the dermal route and Toxicity

Category IV for skin irritation potential. It is not a skin sensitizer. Short- and intermediate-term 

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

all post-application activities. Under 40 CFR 156.208 (c) (2) (iii), ai’s classified as Acute III or 

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

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

to protect agricultural workers from post-application exposures to halosulfuron-methyl. 

9.2.2 Inhalation Postapplication Risk

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

exposure assessment was not performed for halosulfuron-methyl at this time because the 

chemical has low vapor pressure (<1 x 10-7 mmHg at 25oC) and is applied at a low rate (0.0625 

lb ai/A). However, there are multiple potential sources of post-application inhalation exposure to 

individuals performing post-application activities in previously treated fields. These potential 

sources include volatilization of pesticides and resuspension of dusts and/or particulates that 

contain pesticides. The Agency sought expert advice and input on issues related to volatilization 

of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory

Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html) and 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. The Agency may, as appropriate, develop 

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

occupational post-application inhalation exposure into the Agency's risk assessments. If new 

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

occupational post-application inhalation exposure assessment for halosulfuron-methyl.

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

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

handlers. Handler exposure resulting from mixing/loading pesticides is likely to result in higher 

exposure than post-application exposure. Thus, handler inhalation exposure estimates would be 

protective of most occupational post-application inhalation exposure scenarios.

10.0 References

Barrett, M., 03/26/2013, DP404096, Halosulfuron methyl Drinking Water Assessment for 

Additional Food/Feed Uses on Artichokes and Caneberry Subgroup 13-07A.
Halosulfuron-Methyl

Human Health Risk Assessment DP No. 404095

Page 29 of 37

Cheng, L., 11/26/2012, DP405659, Halosulfuron-methyl. Section 3 Registration on Artichoke 

and Caneberry Subgroup 13-07A. Summary of Analytical Chemistry and Residue Data.

Meléndez, J., 05/15/2012, DP394244, Halosulfuron methyl Drinking Water Assessment for 

Additional Food/Feed Uses on Proso Millet, Pasture and Rangeland Grass Forage, Fodder and 

Hay (Crop Group 17).

Negussie, M., 03/11/2013, DP405660, Halosulfuron-methyl. Acute and Chronic Aggregate 

Dietary (Food and Drinking Water) Exposure and Risk Assessments for the Section 3 

Registration Action on Artichoke and Caneberry Subgroup 13-07A.

Smegal, D., 02/22/2012, TXR 0054045, Halosulfuron-methyl: Su mmary of hazard and 

Science Policy Council (HASPOC) Meeting of February 9, 2012: Recommendations on waiver 

requests for 28-day inhlataion study..

Tsaur, N., 02/21/2013, DP404839, Halosulfuron-Methyl. Occupational and Residential

Exposure Assessment for Proposed IR-4 Uses on Caneberry (subgroup 13-07A)and Artichokes. 

Tsaur, N., 06/12/2012, DP396460, Halosulfuron-Methyl. Occupational Exposure Assessment 

for Proposed New Uses on Proso Millet and Crop Group 17 (Grass, Forage, Fodder, and Hay) 

with An Updated Residential Exposure Assessment of All Existing Residential Uses.

Walls, C., 07/19/2012, DP396458, Halosulfuron-Methyl: Human Health Risk Assessment for 

Proposed New Uses on Proso Millet and Crop Group 17 (Grass, Forage, Fodder, and Hay).

.
Halosulfuron-Methyl

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Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.500) for Food Use for Halosulfuron-methyl are in Table 1. Use of the new guideline 

numbers does not imply that the new (1998) guideline protocols were used.

Study

Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity ..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Acute Eye Irritation .......................................................

870.2500 Acute Dermal Irritation .................................................

870.2600 Skin Sensitization ..........................................................

yes

yes

yes

yes

yes

yes

Yes

yes

yes

yes

yes

yes

870.3100 90-Day Oral Toxicity in Rodents ..................................

870.3150 90-Day Oral Toxicity in Nonrodents.............................

870.3200 21/28-Day Dermal Toxicity...........................................

870.3250 90-Day Dermal Toxicity................................................

870.3465 90-Day Inhalation Toxicity ...........................................

yes

yes

yes

no

CR

Yes

yes

yes

-

-

a

870.3700a Prenatal Developmental Toxicity (rodent).....................

870.3700b Prenatal Developmental Toxicity (nonrodent)...............

870.3800 Reproduction and Fertility Effects.................................

yes 

yes 

yes

Yes

yes

yes

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200b Carcinogenicity (mouse)................................................

870.4300 Combined Chronic Toxicity/Carcinogenicity................

no

yes

yes

Yes

yes

yes

870.5100 Mutagenicity—Bacterial Reverse Mutation Test ..........

870.5300 Mutagenicity—Mammalian Cell Gene Mutation Test ..

870.5375 Mutagenicity—Structural Chromosomal Aberrations...

870.5395 Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

Yes

yes

yes

yes

870.6200a Acute Neurotoxicity Screening Battery (rat) .................

870.6200b 90-Day Neurotoxicity Screening Battery (rat)...............

870.6300 Developmental Neurotoxicity........................................

yes

yes

no

Yes

yes

-

870.7485 Metabolism and Pharmacokinetics................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity .............................................................

yes

no

no

Yes

-

no

a Inhalation requirement is waived for the current and proposed uses (D. Smegal, TXR 0054045, 02/22/12)
Halosulfuron-Methyl

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A.2 Toxicity Profiles

Table A.2.1. Acute Toxicity of Halosulfuron-Methyl Technical.

OPPTS 

No.

Study Type MRID Results Toxicity 

Category

870.1100 Acute Oral- Rats 42139413 LD50: Males = 10,435 mg/kg

 Females = 7758 mg/kg

 Combined = 8866 mg/kg

IV

870.1200 Acute Dermal- Rats 42139415 LD50 >2000 mg/kg (limit test) III

870.1300 Acute Inhalation- Rats 42139417 LC50 >6 mg/L IV

870.2400 Primary Eye IrritationRabbits42139419 Mild transient (<24 hr) irritation 

involving the conjunctiva and iris.

IV

870.2500 Primary Skin 

Irritation- Rabbits

42139421 Non-irritant IV

870.2600 Dermal SensitizationGuinea pigs42139423 Not a skin sensitizer (maximization test) N/A

Table A.2.2. Toxicity Profile of Halosulfuron-Methyl Technical.

Guideline 

No.

Study Type MRID No. 

(Date)/Classification/ Doses

Results

870.3100

(82-1)

Subchronic oral 

toxicity study in 

rats 

43616301 (1995)/ 

Acceptable/Guideline

Doses: 0, 100, 1000, 10000, or 

20000 ppm (diet) (M/F: 

6.7/7.6, 66.5/75.8, 682.8/772.8, 

1400/1578 mg/kg/day)

NOAEL = M > 1400, F = 75.8 mg/kg/day

LOAEL = M not determined, F = 772.8 mg/kg/day 

based on decreased body weight gains.

870.3100 

(82-1)

Subchronic oral 

toxicity study in 

rats (28 day rangefinder)

42171501 (1988)/ 

Acceptable/Nonguideline 

Doses: 0, 100, 400, 1600, or 

6400 ppm (diet)

(M/F: 7.4/8.9, 28.8/37.3, 

116/147, 497/640 mg/kg/day)

NOAEL = M = 116, F =147 mg/kg/day

LOAEL = M = 497, F = 640 mg/kg/day based on 

decreased body weight gains, decreased organ weights 

and changes in clinical chemistry parameters.

870.3150 

(82-1)

Subchronic oral 

toxicity study in 

nonrodents - dogs 

42171502 (1991)/ 

Acceptable/Nonguideline

Doses: 0, 2.5, 10, 40, and 160 

mg/kg/day (capsule) 

NOAEL = 10 mg/kg/day

LOAEL = 40 mg/kg/day based on decreased body 

weight gains and food efficiency along with hematology 

and clinical chemistry changes.

870.3200 

(82-2)

21-day dermal 

toxicity in rats

42661417 (1990)/ 

Acceptable/Guideline

Doses: 0, 10, 100, or 1000 

mg/kg/day

NOAEL = 100 mg/kg/day

LOAEL = 1000 mg/kg/day based on a dose-related 

decrease in total body weight gain in males. Total body 

weight gain was also decreased in the 100 mg/kg/day 

group females, but the 1000 mg/kg/day group females 

were comparable to the control group.

870.3465 

(82-4)

90-day inhalation 

study in rats This data requirement has been waived (TXR D. Smegal, TXR 0054045, 02/22/12)

870.4100 

(83-1b) 

Chronic oral 

toxicity study in 

42396211 (1991)/ 

Acceptable/Guideline

NOAEL = 10 mg/kg/day

LOAEL = 40 mg/kg/day based on decreased body
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Table A.2.2. Toxicity Profile of Halosulfuron-Methyl Technical.

Guideline 

No.

Study Type MRID No. 

(Date)/Classification/ Doses

Results

dogs Doses: 0, 0.25, 1.0, 10.0, or 40 

mg/kg/day (capsule).

weight gains in males and females, decreased relative 

food efficiency in females along with hematological and 

clinical chemistry changes. 

870.4300 

(83-5)

Combined 

Chronic/ 

Carcinogenicity in 

rats

42661418 (1992)/ 

Acceptable/Guideline

Doses: 0, 10, 100, 1000, or 

2500, 5000 (males only) ppm 

(diet)

(M/F: 0.44/0.56, 4.4/5.6, 

43.8/56.3, 108.3/138.6, 225.6 

(M) mg/kg/day)

NOAEL = M=108.3, F=56.3 mg/kg/day

LOAEL = M=225.6, F=138.6 mg/kg/day based on 

marginal decrease in body weight gain in both males 

and females.

No evidence of carcinogenicity.

870.4200 

(83-2) 

Carcinogenicity 

study in mice 

42661419 (1992)/ 

Acceptable/Guideline

Doses: 0, 30, 300, 3000, or 

7000 ppm (diet)

(M/F: 4.0/5.2, 41.1/51.0, 

410.0/509.1, or 971.9/1214.6 

mg/kg/day)

NOAEL = M=410.0, F > 1214.6 mg/kg/day

LOAEL = M=971.9, F>1214.6 mg/kg/day based on 

decreased body weight gains and necropsy findings 

(increase incidence of microconcretion/mineralization in 

the testis and epididymis). 

No evidence of carcinogenicity.

870.3700 

(83-3) 

Developmental 

toxicity in rats

42139425 (1990)/ 

Acceptable/Guideline

Doses: 0, 75, 250, or 750 

mg/kg/day (gavage)

Maternal NOAEL = 250 mg/kg/day.

Maternal LOAEL = 750 mg/kg/day, based on increased 

incidence of clinical observations, reduced body weight 

gains, reduced food consumption and food efficiency.

Developmental NOAEL = 250 mg/kg/day. 

Developmental LOAEL = 750 mg/kg/day, based on 

decreased mean fetal body weight and mean litter size, 

increased fetal and litter incidences of soft tissue and 

skeletal variations.

870.3700 

(83-3b)

Developmental 

toxicity study in 

rabbits

42139426 (1990)/ 

Acceptable/Guideline

Doses: 0, 15, 50, or 150 

mg/kg/day (gavage)

Maternal NOAEL = 50 mg/kg/day

Maternal LOAEL = 150 mg/kg/day based on reduced 

body weight gain, food consumption and food 

efficiency.

Developmental NOAEL = 50 mg/kg/day

Developmental LOAEL = 150 mg/kg/day based on 

group decreased mean litter size, increased number of 

resorptions and resorptions per dam, and increased 

postimplantation loss.

870.3700 

(83-3b)

Developmental 

toxicity study in 

rabbits

43621901 (1995) 3-

chlorosulfonamide acid

Metabolite/

Acceptable/Guideline

Doses: 0, 30, 300, or 1000 

mg/kg/day 

Maternal Toxicity NOAEL => 1000 mg/kg/day

Maternal Toxicity LOAEL > 1000 mg/kg/day

Developmental Toxicity NOAEL => 1000 mg/kg/day

Developmental Toxicity LOAEL > 1000 mg/kg/day

870.3800 

(83-4)

Two-Generation 

reproduction study 

in rats

42139427 (1991)/ 

Acceptable/Guideline

Doses: 0, 100, 800, or 3600 

ppm (diet)

( F0 Males: 6.3, 50.4, and 223.2 

mg/kg/day; F0 Females: 7.4, 

58.7, and 261.4 mg/kg/day)

Parental/Systemic NOAEL = M=50.5, F=58.7 

mg/kg/day 

Parental/Systemic LOAEL = M=223.2, F=261.4 

mg/kg/day based on decreased body weights, body 

weight gains, and reduced food consumption during the 

premating period in both sexes.

Offspring NOAEL = 51/59 mg/kg/day

Offspring LOAEL = 223.2/261.4 mg/kg/day based on 

decreased body weight in the F1 pups and marginal 

decreased body weight in F2 pups.
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Table A.2.2. Toxicity Profile of Halosulfuron-Methyl Technical.

Guideline 

No.

Study Type MRID No. 

(Date)/Classification/ Doses

Results

Reproductive NOAEL > = 223.2/261.4 mg/kg/day.

870.6200a 

(82-7)

Acute 

neurotoxicity in 

rats.

45754701 (1994) and 

46199501 (1989)[positive 

control study]/ 

Acceptable/Guideline

Doses: 0, 200, 600, or 2000 

mg/kg (limit dose)

NOAEL = 600 mg/kg. 

LOAEL = 2000 mg/kg (limit dose) based on mortality 

in males. 

870.6200b 

(82-7)

Subchronic 

neurotoxicity 

study in rats.

45754702 (1992)/ 

Acceptable/Guideline

Doses: M: 0, 100, 1000, or 

10,000 ppm; F: 0, 100, 1000, 

or 4000 ppm (diet) (M/F: 0/0, 

6.3/8.1, 62.8/82.6, or 

706.0/315.9 mg/kg/day)

NOAEL = M = F = 1000 ppm (M/F: 62.8/82.6 

mg/kg/day). 

LOAEL = M = 10,000 ppm; F =4000 ppm (M: 706.0 

mg/kg/day) in males based on decreased body weight 

and body weight gain and (F: 315.9 mg/kg/day) in 

females based on decreased body weight gain. 

870.7485

(83-6)

Metabolism 42139433 (1990)/ 

Acceptable/Guideline

5 or 250 mg/kg single dose or 

5 mg/kg/day repeated doses

Absorption was rapid, incomplete and similar in both 

sexes. Elimination was mostly by urine and feces 

within 72 hours, appearing to be independent of dose 

and sex. Desmethyl NC-319 and the 5-hydroxy 

derivative were the major urinary and fecal metabolites.

870.7800(

83-6)

Immunotoxicity A waiver request for this data requirement has been submitted and is under review.

870.5100 

(84-2 a) 

Mutagenic - Ames

Salmonella

typhimurium and 

E. Coli.

42139428 (1991)/ Acceptable 

(+/-S9) 5 strains S. typh. 

Conc.: 1 - 10000 

microgm/plate; E. Coli 

WpuvrA Conc.: 333 - 10000 

microgram/plate

Negative. Concentrations => 5000 microgm/plate found 

to be insoluble and/or cytotoxic.

870.5100 

(84-2 a) 

Mutagenic - Gene 

Mutation

43616302 (1995)/ Acceptable 

(+/-S9) 5 strains S. typh. 

Conc.: 50 - 5000 

microgm/plate

Negative. Conducted with 3-chlorosulfonamide acid-the 

principal soil metabolite of halosulfuron-methyl.

870.5300 

(84-2)

Mutagenic - Gene 

Mutation -

Hamster (Chinese)

43616303 (1995) - Metabolite/

Acceptable 

(+/-S9) Conc.: 350-3100 

microgm/mL

Negative. Conducted with 3-chlorosulfonamide acid-the 

principal soil metabolite of halosulfuron-methyl.

870.5300 

(84-2)

Mutagenic -

(HGPRT) -

Hamster 

(Chinese).

42139431 (1991) - Metabolite/

Unacceptable 

Conc.: 100-1000 microgm/mL

Conclusions indefinite due to partly to relatively high 

negative and low positive control values, solubility 

problems with test article.

870.5300 

(84-2)

Mutagenic -

(HGPRT) -

Hamster 

(Chinese).

42661420 (1993)/ Acceptable 

(+/-S9) Conc.: 50-900 

microgm/mL

Negative. Did not induce forward mutations at the 

HGPRT locus in Chinese Hamster ovary cells. 

Concentrations above 700 ug/mL were insoluble.

870.5375 

(84-2)

Mutagenic - In 

vitro Clastogenic -

Hamster (Chinese) 

42139429 (1989)/ Acceptable 

(+/-S9) Conc.: 449-1810 

microgm/mL

Negative. No chromosomal aberrations.
Halosulfuron-Methyl

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Page 34 of 37

Table A.2.2. Toxicity Profile of Halosulfuron-Methyl Technical.

Guideline 

No.

Study Type MRID No. 

(Date)/Classification/ Doses

Results

870.5395 

(84-2)

Mutagenic -

Micronucleus 

Assay - Mouse 

(CD-1)

43616304 (1995) -

Metabolite/Acceptable

Doses: 1250, 2500 or 5000 

mg/kg

Negative. Conducted with 3-chlorosulfonamide acidthe principal soil metabolite of halosulfuron-methyl. No 

overt toxicity for the treated animals or cytotoxicity for 

the target organ (bone marrow cells) was observed.

870.5395 

(84-2)

Mutagenic -

Micronucleus 

Assay - Mouse

42139430 (1989)/ Acceptable 

Doses: 500, 1667 0r 5000 

mg/kg.

Negative. Did not induce significant elevations in the 

frequencies of micronucleated polychromatic 

erythrocytes.

870.5500 

(84-2)

Mutagenic -

Unscheduled DNA 

synthesis - Rat

42139432 (1990)/ Acceptable

(+/-S9) Conc.: 25-1000 

microgm/mL

Negative. Fail to induce unscheduled DNA synthesis in 

primary rat hepatocytes. 
Halosulfuron-Methyl

Human Health Risk Assessment DP No. 404095

Page 35 of 37

Appendix B. Physical/Chemical Properties

Table C1. Physicochemical Properties of Halosulfuron-methyl.

Parameter Value Reference

Melting point/range 175.5-177.2 oC MRID 42139403; DP#s 

173627 & 180565, 7/30/92, 

G.J. Herndon

pH 4.11 at 25 oC (1% w/v slurry)

Density 1.618 g/mL at 25 oC

Water solubility at 20 oC pH 5 0.0015 g/100 mL

pH 7 0.165 g/100 mL

pH 9 0.747 g/100 mL

Solvent solubility at 20 oC methanol 0.1616 g/100 mL

n-hexane 0.001278 g/100 mL

Vapor pressure <1 x 10-7 mm Hg at 25 oC

Dissociation constant, Ka 3.61 x 10-4at 22.4 oC

Octanol/water partition coefficient, 

Log(KOW) at 23 oC

1.67 at pH 5

-0.0186 at pH 7

-0.542 at pH 9

UV/visible absorption spectrum Not available
Halosulfuron-Methyl

Human Health Risk Assessment DP No. 404095

Page 36 of 37

Appendix C. 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 to determine their dermal and inhalation exposure. Many

such studies, involving exposure to many different pesticides, comprise generic pesticide 

exposure databases such as PHED and the Outdoor Residential Exposure Task Force (ORETF). 

EPA has reviewed all the studies supporting these multi-pesticide generic exposure databases, 

and has found no clear and convincing evidence that the conduct of any of them was either 

fundamentally unethical or significantly deficient relative to the ethical standards prevailing at 

the time the research was conducted. All applicable requirements of EPA’s Rule for the 

Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied, and there is no 

regulatory barrier to continued reliance on these studies.
Halosulfuron-Methyl

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Page 37 of 37

Appendix D. International Residue Limits

Halosulfuron-methyl (PC Code 128721); 10/31/2012

Table A.1 Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex

40 CFR 180.479 (a) (2):

Tolerances are established for residues of 

the herbicide halosulfuron-methyl, methyl 

3-chloro-5-[[[[(4,6-dimethoxy-2-

pyrimidinyl)amino]carbonyl]amino]sulfon

yl]-1-methyl-1H-pyrazole-4-carboxylate, 

including its metabolites and degradates, in 

the table below. Compliance with the 

tolerance levels specified in the following 

table is to be determined by measuring 

only halosulfuron-methyl.

None None

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex

Artichoke 0.05

Caneberry subgroup 13-07A 0.05

Completed: M. Negussie; 11/21/2012

1

Includes only commodities of interest for this action. Tolerance values should be the HED 

recommendations and not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.