Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 2 of 44

1.0 Executive Summary ........................................................................................................... 4

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

2.1 Data Deficiencies and Requirements Prior to Registration ....................................... 7

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

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

2.2.2 International Harmonization..................................................................................... 8

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

2.2.4 Revisions to Petitioned-For Tolerances.................................................................... 9

2.3 Label Recommendations................................................................................................ 9

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

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

2.3.3 Recommendations from Residential Assessment................................................... 10

3.0 Introduction...................................................................................................................... 10

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

3.2 Physical/Chemical Characteristics ............................................................................. 12

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

3.4 Anticipated Exposure Pathways................................................................................. 15

3.5 Consideration of Environmental Justice.................................................................... 16

4.0 Hazard Characterization and Dose-Response Assessment.......................................... 16

4.1 Summary of Toxicological Effects.............................................................................. 16

4.2 Safety Factor for Infants and Children (FQPA Safety Factor) ............................... 17

4.2.1 Completeness of the Toxicology Database.............................................................. 17

4.2.2 Evidence of Neurotoxicity ........................................................................................ 18

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal........ 18

4.2.4 Residual Uncertainty in the Exposure Database ................................................... 18

4.3 Toxicity Endpoint and Point of Departure Selections .............................................. 19

5.0 Dietary Exposure and Risk Assessment......................................................................... 20

5.1 Residues of Concern Summary and Rationale .......................................................... 20

5.2 Food Residue Profile .................................................................................................... 21

5.3 Water Residue Profile.................................................................................................. 23

5.4 Dietary Risk Assessment.............................................................................................. 23

5.4.1 Description of Residue Data Used in Dietary Assessment.................................... 24

5.4.2 Percent Crop Treated Used in Dietary Assessment .............................................. 24

5.4.3 Acute Dietary Risk Assessment............................................................................... 24

5.4.4 Chronic Dietary Risk Assessment........................................................................... 24

5.4.5 Cancer Dietary Risk Assessment............................................................................. 24

5.4.6 Summary Table......................................................................................................... 25

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 25

6.1 Residential Handler Exposure .................................................................................... 25

6.2 Post-Application Exposure .......................................................................................... 26

6.3 Combined Exposure..................................................................................................... 27

6.4 Residential Bystander Post-application Inhalation Exposure ................................. 28

6.5 Spray Drift.................................................................................................................... 28

7.0 Aggregate Exposure/Risk Characterization.................................................................. 29

7.1 Acute Aggregate Risk................................................................................................... 29

7.2 Short-Term Aggregate Risk ........................................................................................ 29
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 3 of 44

7.3 Intermediate-Term Aggregate Risk ........................................................................... 30

7.4 Chronic Aggregate Risk .............................................................................................. 30

7.5 Cancer Aggregate Risk ................................................................................................ 30

8.0 Cumulative Exposure/Risk Characterization ............................................................... 30

9.0 Occupational Exposure/Risk Characterization ............................................................ 30

9.1 Short-/Intermediate-Term Handler Risk................................................................... 30

9.2 Short-/Intermediate-Term Post-Application Risk .................................................... 36

9.2.1 Dermal Post-Application Risk................................................................................. 36

9.2.2 Inhalation Post-application Risk............................................................................. 37

10.0 References......................................................................................................................... 38

Appendix A. Toxicology Profile................................................................................................ 39

A.1 Toxicology Data Requirements................................................................................... 39

A.2 Toxicity Profiles............................................................................................................ 40

Appendix B. International Residue Limits.............................................................................. 44
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 4 of 44

1.0 Executive Summary

On behalf of Canyon Group L.L.C. (Canyon), Gowan Company (Gowan) is proposing to add 

new uses of the active ingredient (ai), halosulfuron-methyl, on proso millet and crop group 17 

(grasses, forage, fodder, and hay). 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 2010 for the uses on 

succulent and dried shelled peas/ beans, tuberous and corm vegetables, bushberries, okra, apples, 

and rhubarb (D366410, W. Phang, 4/5/10). In accordance with the 2007 revised 40 CFR Part 

158 Toxicology data requirements, an immunotoxicity study and a subchronic inhalation toxicity 

study were required for halosulfuron methyl. However, HED has waived the inhalation toxicity 

study data requirement at this time (TXR0054045). 

Pending submission of revised Sections B and F, and an analytical standard for the 

rearrangement ester (RRE) of halosulfuron-methyl, there are no additional toxicology or residue 

chemistry issues that would preclude granting unconditional registration for the requested uses of 

halosulfuron-methyl on proso millet and crop group 17 (grasses, forage, fodder, and hay).

Proposed Use Profile

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

postemergence broadcast foliar sprays using ground or aerial equipment. Application through 

any type of irrigation system is prohibited. Halosulfuron-methyl may be applied to proso millet 

once per season at a maximum application rate of 4 oz/A (0.0313 lb ai/A). For pasture and 

rangeland (crop group 17), halosulfuron-methyl may be applied once per season at a maximum 

application rate of 8 oz/A (0.0625 lb ai/A). The restricted entry interval (REI) is 12 hours. 

These new uses are proposed to be added to three end-use product (EP) labels: Yukon Herbicide 

(EPA Reg. No. 81880-6) with 12.5% ai by weight, 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

Exposures to halosulfuron methyl are expected to occur for acute-, short- , intermediate-, and 

long-term (chronic) exposures. The proposed agricultural uses on proso millet and crop group 

17 (grasses, forage, fodder, and hay) would result in new exposures in both food and drinking 

water. There are also existing residential uses that would result in non-occupational exposure 

from handler and post-application activities. In occupational settings, exposure is also expected 

during handler and post-application activities. 

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 nonirritant for skin and eyes (Toxicity Category IV) and is not a dermal sensitizer. With repeated 
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 5 of 44

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 similar 

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

weight and food consumption in maternal animals were observed. However, a clear NOAEL for 

these effects was established in both rat and rabbit developmental toxicity studies. Halosulfuronmethyl 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 which was required as a condition of registration. The 28-day inhalation 

toxicity study, also a condition of registration, was 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 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, and an acute dietary exposure assessment was only conducted for females 13-49 years old. 

Conservative acute and chronic dietary exposure assessments were performed for halosulfuronmethyl 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, 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 6% of the cPAD for all infants, 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 is neither expected nor assessed. 
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 6 of 44

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.

Residential Handler: Residential short-term (1 - 30 days) dermal and inhalation exposures are 

expected from handler activities associated with the existing uses. HED used data from ORETF 

and PHED Version 1.1 to assess residential handler exposures. MOEs greater than 100 are

deemed adequate to protect residential halosulfuron-methyl handlers. Short-term combined 

(dermal + inhalation) residential handler MOEs range from 7,200 to 190,000 and, therefore, are 

not of concern. 

Residential Post-application: Residential short- term dermal and incidental oral exposures are 

expected from post-application activities associated with the existing uses. MOEs greater than 

100 are deemed adequate to protect adults and children from post-application residues of 

halosulfuron-methyl. Short-term post-application MOEs for all residential scenarios range from 

1,000 to 11,000,000 and, therefore, 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 and do not exceed 

HED’s LOC. For proso millet, the baseline short-term combined (dermal + inhalation) MOEs 

range from 3,000 to 140,000. Intermediate-term exposure is unlikely due to the agricultural 

practices of millet. For pasture and rangeland, the baseline short-term combined (dermal + 

inhalation) MOEs range from 15,000 to 71,000 and the baseline intermediate-term combined

MOEs range from 200 to 9,600.

Agricultural Post-application: There is potential for short- and intermediate-term occupational 

exposure during post-application activities. There are no risk estimates of concern on day 0 (12 

hours after application); all scenarios resulted in MOEs greater than the LOC of 100 (ranging 

from 400 to 160,000) on day 0 (12 hours after application). Based on a quantitative postapplication assessment, the 12-hour REI on the proposed label is acceptable.

HED assumes that post-application inhalation exposures are minimal following applications of 

an ai with low vapor pressure. Since halosulfuron-methyl has low acute inhalation toxicity 

(Toxicity Category IV) and a low vapor pressure, post-application inhalation exposures and risk

estimates were not quantitatively assessed.
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 7 of 44

Environmental Justice Considerations: Potential areas of environmental justice concerns, to 

the extent possible, were considered in this human health risk assessment. Dietary and nondietary 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 data, 

the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler 

Exposure Task Force (AHETF) database; the Outdoor Residential Exposure Task Force 

(ORETF) database; and the Agricultural Re-entry Task Force (ARTF) database, are subject to 

ethics review pursuant to 40 CFR 26, have received that review, and are compliant with 

applicable ethics requirements. For certain studies that review may have included review by the 

Human Studies Review Board. Descriptions of data sources as well as guidance on their use can 

be found at http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

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

2.0 HED Recommendations

Provided revised Sections B (OPPTS 860.1200), F (OPPTS 860.1550), and an analytical 

reference standard for the RRE of halosulfuron-methyl are submitted, HED can recommend 

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

millet and pasture and rangeland grasses. Additional data are needed prior to the registration as 

outlined in Section 2.1 below. The specific tolerance recommendations are discussed in Section 

2.2, and label modifications are discussed in Section 2.3.

2.1 Data Deficiencies and Requirements Prior to Registration

The following must be provided prior to a tolerance being established or registration 

allowed:

860.1200 Directions for Use

For all labels, the preharvest interval (PHI) and pregrazing interval (PGI) for millet 

forage should be revised to 0-day PHI.

All labels should be revised to:

o Specify a 37-day PHI for proso millet hay and a 50-day PHI for proso millet grain 

and straw.

o Specify a 0-day PGI for grass forage for all animals (beef, lactating and nonlactating).

o Because crop oil concentrates (COC) were not used in any of the submitted crop 

field trials on proso millet or grass, the labels for the 12.5% and 75% WG 

formulations should be revised to state that only non-ionic surfactants (NIS) 

adjuvants may be added to the spray mixtures for these crops. 

o Remove the recommended 30-day pre-slaughter interval (PSI).

860.1550 Proposed Tolerances

A revised Section F must be submitted to reflect the tolerances and correct commodity 

definitions as listed in Table 2.2.4.
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 8 of 44

860.1650 Submittal of Analytical Reference Standards

An analytical reference standard for the RRE of halosulfuron-methyl must be submitted 

to the EPA National Pesticide Standards Repository.

The following data are required as a condition of registration:

TOXICOLOGY

870.7800 Immunotoxicity Study

The Immunotoxicity study is required to fulfill current 40 CFR Part 158 data 

requirements. This study was called in as a condition of registration in the most recent 

risk assessment (D366410, W. Phang, 4/5/10). 

The following data should be submitted with future uses:

RESIDUE CHEMISTRY

860.1480 Meat/Milk/Poultry/Eggs

If future new use requests increase the dietary burden, a new dairy cattle feeding study 

will be needed.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Adequate analytical methods are available for the enforcement of tolerances for residues of 

halosulfuron-methyl in plants (Method RES-109-97-4), and for residues of halosulfuron-methyl 

and its 3-CSA metabolites in livestock commodities (Method RES-046-93). Samples from the 

submitted field trial studies were analyzed for residues of halosulfuron-methyl using a modified 

version of the plant enforcement method (gas chromatography with nitrogen phosphorus or mass 

selective detection; GC/NPD or GC/MSD) with a petitioner-validated limit of quantitation 

(LOQ; determined as the lowest level of method validation; LLMV) of 0.01 ppm. The method 

was adequate for data collection based on acceptable concurrent method recoveries, and the 

fortification levels used in concurrent method recovery were adequate to bracket expected 

residue levels.

Residues of halosulfuron-methyl and 3-CSA are not adequately recovered by FDA Multiresidue 

Method protocols. The results have been forwarded to FDA.

2.2.2 International Harmonization

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

residues of halosulfuron-methyl in crop or livestock commodities. An International Residue 

Limit Status sheet is attached (Appendix B).
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 9 of 44

2.2.3 Recommended Tolerances

HED recommends for the following tolerances listed in Table 2.2.3.

Table 2.2.3. Tolerance Summary for Halosulfuron-Methyl.

Commodity Proposed/Existing

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

Millet, proso, forage 7.0 10 The data supports a tolerance of 10 ppm 

with a 0-day PHI/PGI.

Millet, proso, hay 0.02 0.01

Millet, proso, grain 0.01 0.01

Millet, proso, straw 0.01 0.01

Grass forage, fodder, and 

hay, Crop group 17 forage

17 20 Grass, forage, fodder, and hay, group 17, 

forage

Grass forage, fodder, and 

hay, Crop group 17 hay

0.90 0.5 Grass, forage, fodder, and hay, group 17, 

hay

Additional Livestock Commodity Tolerances That Need to be Proposed/Established

Cattle, meat byproducts 0.1 1.0

Goat, meat byproducts 0.1 1.0

Horse, meat byproducts 0.1 1.0

Sheep, meat byproducts 0.1 1.0

Additional Livestock Commodity Tolerances That Need to be Proposed/Established

Cattle, fat None 0.05

Cattle, meat None 0.05

Goat, fat None 0.05

Goat, meat None 0.05

Horse, fat None 0.05

Horse, meat None 0.05

Milk None 0.05

Sheep, fat None 0.05

Sheep, meat None 0.05

2.2.4 Revisions to Petitioned-For Tolerances

Table 2.2.3 compares proposed and recommended tolerance levels. The recommended plant 

commodity tolerance levels are based on the submitted magnitude of the residue data and the 

Agency’s tolerance spreadsheet as specified by the Guidance for Setting Pesticide Tolerances 

Based on Field Trial Data SOP. Differences in proposed and recommended tolerances may be 

attributed to the petitioner having used the North American Free Trade Agreement (NAFTA) 

tolerance calculation procedures for determining the tolerance and HED’s use of the OECD 

tolerance calculation procedures; for grass hay, the petitioner used values below the LOQ in the 

tolerance calculation whereas HED used LOQ values. Livestock tolerances are derived from 

reevaluation of the dairy/beef cattle diet with new feed items (millet and grass).

2.3 Label Recommendations
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 10 of 44

2.3.1 Recommendations from Residue Reviews

The following label revisions are needed:

For all labels, the PHI/PGI for millet forage should be revised to 0-day PHI.

All labels should be revised to:

o Specify a 37-day PHI for proso millet hay and a 50-day PHI for proso millet grain 

and straw.

o Specify a 0-day PGI for grass forage for all animals (beef, lactating and nonlactating).

o Because COC were not used in any of the submitted crop field trials on proso 

millet or grass, the labels for the 12.5% and 75% WG formulations should be 

revised to state that only NIS adjuvants may be added to the spray mixtures for 

these crops. 

o Remove the recommended 30-day PSI.

2.3.2 Recommendations from Occupational Assessment

Throughout the GWN-3061 (EPA Reg. No. 81880-2) label, the instructions often reference the 

Sandea® (EPA Reg. No. 81880-18) label. These references should be corrected. 

2.3.3 Recommendations from Residential Assessment

None

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 §180.479 at levels ranging from 0.05 to 2.0 ppm. 

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

as emulsifiable concentrates.

The petitioner, Canyon Group LLC (agent Gowan Company) has submitted a request for 

amended registration of a 12.5% water dispersible granule (WG) formulation of halosulfuronmethyl (Yukon Herbicide; EPA Reg. No. 81880-6; MAI containing 55% dicamba) and two 75% 

WG formulations (Sandea Herbicide, EPA Reg. No. 81880-18, and GWN-3061, EPA Reg. No. 

81880-2) for use on proso millet and pasture and rangeland grasses. The proposed uses reflect 

foliar broadcast application to proso millet at 0.023-0.0313 lb ai/A or to pasture and rangeland 

grasses at 0.0313-0.0625 lb ai/A. The proposed PHIs/PGIs range from 0 days to 37 days for 

millet commodities and pasture grass; no PHI has been proposed for millet grain and straw.
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 11 of 44

3.1 Chemical Identity

The chemical structure and nomenclature of halosulfuron-methyl and the 3-chlorosulfonamide 

moiety (3-CSA) are presented in Table 3.1. 

Table 3.1. Halosulfuron-Methyl 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% WDG (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

Rearrangement ester (RRE) of 

halosulfuron-methyl

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

N

N

O

CH3

O

CH3

N

H

N

N

CH3

Cl

O

O

CH3
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 12 of 44

3.2 Physical/Chemical Characteristics

The physicochemical properties of the technical grade of halosulfuron-methyl are presented in 

Table 3.2. 

The octanol/water partition coefficient suggests that halosulfuron-methyl 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

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

broadleaf weeds and nutsedge. The end-use products (EPs) relevant to this registration action are 

Yukon Herbicide (EPA Reg. No. 81880-6), Sandea® Herbicide (EPA Reg. No. 81880-18) and 

GWN-3061 Herbicide (EPA Reg. No. 81880-2). These products are currently registered to 

Gowan Company and are classified as WDG formulations. Sandea® Herbicide and GWN-3061 

Herbicide contain 75% halosulfuron-methyl, whereas, Yukon Herbicide contains 12.5% a.i. 

The petitioner is proposing to add the proso millet and crop group 17 (grasses, forage, fodder, 

and hay) to the three labels. The proposed use patterns are presented in Table 3.3.

 

Table.3.2. Physicochemical Properties of Halosulfuron-Methyl.

Parameter Value Reference

Melting point/range 175.5-177.2 oC MRID 42139403; D173627 

& D180565, 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. 396458

Page 13 of 44

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

Applic. Timing, 

Type, and 

Equip.

Formulatio

n

[EPA

Reg. No.]

Applic. 

Rate

oz/A

(lb ai/A)

Max. No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. 

Rate

oz/A

(lb ai/A) 

PHI/PGI1

(Days)

Use Directions and 

Limitations2

Proso Millet

Post weed 

emergence and 

actively growing 

weeds;

Foliar,

Broadcast,

Ground or 

aerial;

12.5% WG

[81880-6]

3-4 oz/A 

(0.0234-

0.0313)

Not 

specified 

(NS)

4 oz/A 

(0.0313)

Forage

Beef & nonlactating:

0

Lactating 

dairy:

7

Hay

37

Apply at the 3- to 5-leaf stage. 

A PSI of 30 days is specified 

for beef and non-lactating 

animals.

Master Label:

Apply in minimum spray 

volumes of 5 - 15 gal/A (GPA)

by air or 10 GPA by ground.

Do not apply through any type 

of irrigation system. 

Avoid disturbing (cultivation) 

treated areas for at least 7-days 

following application.

A non-ionic surfactant is 

required at 0.25 to 0.5% v/v or 

a crop oil concentrate may be 

used instead at 1% v/v.

Post weed 

emergence and 

actively growing

weeds;

Foliar,

Broadcast,

ground or band 

application, 

aerial

75% WG

[81880-18]

0.5-0.67 

(0.0234-

0.0313)

NS 0.67

(0.0313)

0 Apply at the 2-leaf through 

layby stage (before grain head 

emergence).

Master Label:

Ground (min. 15 gal/A) or 

aerial (3-15 gal/A).

Do not apply using air assisted 

(air blast) field crop sprayers.

Do not apply through any type 

of irrigation system. 

Do not apply more than 2 oz/A 

per 12 month period (includes 

applications to the crop and to 

row middles/furrows).

A non-ionic surfactant is 

recommended at 0.25 to 0.5% 

v/v or a crop oil concentrate at 

1% v/v.

Use of a COC or silicone-based 

adjuvants can result in crop 

injuryand reduced yields and 

are not recommended for 

postemergence.
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 14 of 44

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

Applic. Timing, 

Type, and 

Equip.

Formulatio

n

[EPA

Reg. No.]

Applic. 

Rate

oz/A

(lb ai/A)

Max. No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. 

Rate

oz/A

(lb ai/A) 

PHI/PGI1

(Days)

Use Directions and 

Limitations2

Post weed 

emergence and 

actively growing

weeds;

Foliar,

Broadcast,

ground or band 

application, 

aerial

75% WG

[81880-2]

0.5-0.67 

(0.0234-

0.0313)

NS 0.67

(0.0313)

0 Apply at the 2-leaf through 

layby stage (before grain head 

emergence).

Master Label:

Apply in minimum 

spray volumes of 3 - 15 GPA 

by air or 10 GPA by ground.

Do not apply through any type 

of irrigation system. 

Avoid disturbing (cultivation) 

treated areas for at least 7-days 

following application.

A non-ionic surfactant is 

required at 0.25 to 0.5% v/v or 

a crop oil concentrate may be 

used instead at 1% v/v.

Pasture and Rangeland Grasses

Post weed 

emergence; 

Foliar,

Broadcast,

Ground or 

aerial;

12.5% WG

[81880-6]

4-8 oz/A

(0.0313-

0.0625)

NS 8 oz/A

(0.0625)

Forage

Beef & nonlactating:

0

Lactating 

dairy:

14

Hay

37

A PSI of 30 days is specified 

for beef and non-lactating 

animals.

Same as the master label under 

proso millet.
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 15 of 44

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

Applic. Timing, 

Type, and 

Equip.

Formulatio

n

[EPA

Reg. No.]

Applic. 

Rate

oz/A

(lb ai/A)

Max. No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. 

Rate

oz/A

(lb ai/A) 

PHI/PGI1

(Days)

Use Directions and 

Limitations2

Postemergence3

Foliar broadcast

Ground

or aerial 

75% WG

[81880-18]

0.67-1.33

(0.0313-

0.0625

NS 1.33

(0.0625)

Forage

Beef & nonlactating:

0

Lactating 

dairy:

14

Hay

37

Apply to established pasture 

and rangeland. A PSI of 30 

days is specified for beef and 

non-lactating animals.

Ground (min. 10 gal/A) 

Same as the master label under 

proso millet, except for ground 

application use min. 10 gal/A.

Postemergence3

Foliar broadcast

Ground

or aerial 

75% WG

[81880-2]

0.67-1.33

(0.0313-

0.0625

NS 1.33

(0.0625)

Forage

Beef & nonlactating:

0

Lactating 

dairy:

14

Hay

37

Apply to established pasture 

and rangeland. A PSI of 30 

days is specified for beef and 

non-lactating animals.

Same as the master label under 

proso millet.

1 The proposed use pattern as described in the petition materials under “Residue Chemistry including Reasonable 

Grounds in Support of Petition” indicates that the proposed pregrazing intervals are: 7 days for all animals for proso 

millet; and 7 days for lactating animals and 0 days for all other animals for pasture and rangeland grasses. 

2

PSI = Preslaughter interval. 

3 The labels for the 75% WG formulations also include directions for spot treatment applications to grasses which 

are not presented herein.

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 proso millet and crop group 17 (grasses, forage, 

fodder, and hay). Humans may be exposed to halosulfuron-methyl in food and drinking water, 

since halosulfuron-methyl may be applied directly to growing crops and application may result 

in halosulfuron-methyl 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 postapplication exposure for workers re-entering treated fields. 

Risk assessments have been previously conducted for halosulfuron-methyl, dated 4/5/10 

(D366410, W. Phang). 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. 
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 16 of 44

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.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from 

pesticide exposures that are based on patterns of that subgroup’s food and water consumption, 

and activities in and around the home that involve pesticide use in a residential setting. 

Extensive data on food consumption patterns are compiled by the USDA under the Continuing 

Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all 

registered food uses of a pesticide. These data are analyzed and categorized by subgroups based 

on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to 

assess dietary exposure to smaller, specialized subgroups and exposure assessments are 

performed when conditions or circumstances warrant. Whenever appropriate, non-dietary 

exposures based on home use of pesticide products and associated risks for adult applicators and 

for toddlers, youths, and adults entering or playing on treated areas postapplication 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 peas/beans, tuberous 

and corm vegetables, bushberry, okra, apples, and rubarb (W. Phang, 04/05/10, D366410). Since 

then, no new toxicology data have been submitted. 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 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 GI tract. Within 72 hours, the absorbed 

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 
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 17 of 44

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 seen in the presence 

of decreases in body weight and food consumption in maternal animals were observed. 

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.

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)

A detailed analysis of the data supporting HED’s FQPA evaluation is presented in a previous 

risk assessment (D331643, M. Rust, 9/21/06). No additional data have been submitted and no 

new policy changes have been implemented that would change the conclusions of the 2006 risk 

assessment. With the exception of the data requirement for an immunotoxicity study, the 

conclusions regarding the FQPA Safety Factor in the previous risk assessment are applicable to 

the current action and are summarized below. HED has determined that reliable data show it 

would be safe for infants and children to reduce the FQPA safety factor to 1X. 

4.2.1 Completeness of the Toxicology Database

The toxicology database for halosulfuron-methyl is sufficient and of good quality. However, 40 

CFR §158 requires an immunotoxicity study (OPPTS Guideline 870.7800) for pesticide 

registration. 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 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.

Further, the 28-day inhalation toxicity study, also a condition of registration, was waived 

(Hazard and Science Policy Council (HASPOC) Meeting, TXR # 0054045, DP# D397243, D. 

Smegal, MPH, 2/22/12).
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 18 of 44

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, 28-day dermal) or chronic studies. No neurotoxic 

effects were observed during the acute or subchronic neurotoxicity battery 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 was 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 limit-dose. 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 a screening level analysis. The assessments utilized tolerance level residues for all 

crops. In addition, default processing factors were assumed 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 EFED for 

ground water or surface water. For these reasons it can be concluded that the DEEM-FCID 

analysis does not underestimate risk from chronic 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 personal protective equipment (PPE), and standard values for unit 

exposures and acreage treated/amount handled.
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 19 of 44

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. The use of a POD 

derived from oral toxicity study on halosulfuron-methyl yielded MOEs as low as 4,100 for 

occupational inhalation exposure and it was protective of the potential inhalation exposure for 

the proposed uses.

Table 4.3.1. Toxicological Doses and Endpoints for Halosulfuron-Methyl for Non-Occupational and 

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)

N/A N/A N/A 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.
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 20 of 44

Table 4.3.1. Toxicological Doses and Endpoints for Halosulfuron-Methyl for Non-Occupational and 

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. Absorption via the inhalation route is presumed to be equivalent to oral absorption.

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

5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale

The residues of concern for dietary risk assessment and the tolerance expression are summarized 

in Table 5.1. The residue of concern in plants is the parent compound, halosulfuron-methyl.

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-chlorosulfonamide moiety (3-CSA) by converting residues to 3-CSA, tolerances 

for residues in livestock commodities are expressed in terms of halosulfuron-methyl and its 

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

The parent compound is an adequate for enforcement, and is the only residue included in the 

tolerance expression. The 3-CSA metabolites are also a major residue found in livestock 

commodities and is included in the dietary risk assessment. Based on the environmental fate 

data, halosulfuron methyl is the only residue included in the drinking water assessment. Further 

information on the metabolism and degradation may be found in the risk assessment dated 4/5/10 

(W. Phang, D366410).
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 21 of 44

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

5.2 Food Residue Profile

Crop Field Trials

The submitted magnitude of the residue data, summarized in Table 5.2.1, are adequate for risk 

assessment and tolerance assessment. For all crops, the number and locations of field trials are 

adequate. The proso millet trials reflect a single foliar broadcast application of a WG 

formulation at a target application rate of 0.0313 lb ai/A; a non-ionic surfactant (NIS) was used 

in all trials. The pasture and rangeland grasses trials reflect a single foliar broadcast application 

of a WG formulation of halosulfuron-methyl at a target application rate of 0.0625 lb ai/A; an NIS 

was used in all trials. The Agency’s tolerance spreadsheet, as specified by the Guidance for 

Setting Pesticide Tolerances Based on Field Trial Data SOP, was used to determine appropriate 

tolerance levels. 

The available proso millet data will support tolerances at the LOQ of 0.01 ppm for proso millet 

hay, grain, and straw commodities, provided the petitioner proposes a PHI of 50 days for grain 

and straw. Quantifiable residues were observed in/on forage harvested at 0- and 7-day PHIs. 

Using the OECD tolerance calculation procedures, the recommended tolerances are: 10 ppm (0-

day PHI) for millet forage, 20 ppm for grass forage (based on a 0-day PGI) and 0.5 ppm for grass 

hay. HED recommends a tolerance of 10 ppm for millet forage based on residue data using 0-

day PHI. The differences in the proposed and recommended tolerances for these commodities 

are due to the petitioner having used the NAFTA tolerance calculation procedures in determining 

the proposed tolerances. For grass hay, the petitioner used values below the LOQ in the 

tolerance calculation whereas HED used LOQ values.
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 22 of 44

Table 5.2.1. Summary of Residue Data from Proso Millet Crop Field Trials with Halosulfuron-methyl.

Commodity Total

Rate

lb ai/A

(kg ai/ha)

PHI 

(days)

Residue Levels (ppm)1

n Sample 

Min.

Sample 

Max.

LAFT2 HAFT2 Median Mean Std. 

Dev.

PROSO MILLET (proposed use = 0.0313 lb ai/A total application rate; 

PHIs/PGIs = 0 or 7 days (forage) and 37 days (hay)3

Forage 0.0310-0.0314

(0.0347-0.0352)

0 5 2.37 5.81 2.42 5.04 2.76 3.14 1.08

7 5 0.0231 0.640 0.0261 0.634 0.0744 0.179 0.256

Hay 36-37 5 <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

Grain 51-67 5 <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

Straw 51-67 5 <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

PASTURE AND RANGELAND GRASSES (proposed use = 0.0625 lb ai/A total application rate;

PHIs/PGIs = 0 or 14 days (forage) and 37 days (hay)4

Grass forage 0.0622-0.0651

(0.0697-0.0730)

0 12 3.06 11.2 3.24 11.0 6.52 6.66 2.69

6-7 12 0.0252 4.89 0.0269 4.57 0.972 1.46 1.50

Grass hay 23-37 12 <0.01 0.389 <0.01 0.384 0.0329 0.0702 0.109

1 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, 

mean, and standard deviation, the LOQ (0.01 ppm) was used for any results reported as <LOQ in Table C.3. N/A = 

Not applicable. 

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

3

It is not clear whether the petitioner intends to support a PHI/PGI of 0 days, 7 days, or both for millet forage (refer 

to 860.1200 for additional details); no PHI has been proposed for grain and straw.

4

Per OCSPP 860.1000 Table 1, a 0-day PHI/PGI is required for grass forage. 

Processing Studies

There are no proposed uses that are relevant to this guideline topic.

Storage Stability

Adequate storage stability data for halosulfuron methyl are available to validate the storage 

conditions and durations of storage of samples from the crop field trial and processing studies. 

Corrections to residue values from the residue trials to account for dissipation during storage are 

not necessary.

Meat, Milk, Poultry, and Eggs

There are animal feedstuffs associated with the proposed uses on proso millet and grasses. An 

acceptable feeding study was previously submitted reflecting dosing of lactating dairy cows with 

halosulfuron-methyl at 0.5, 1.5, and 5 ppm in the daily diet on a dry weight basis. In the study, 

no quantifiable residues (<0.01 ppm) were found in milk, muscle, or fat at any feeding level; 

quantifiable residues were found in liver and kidney at all feeding levels. With the recalculated 

dietary burden for dairy cattle (from 0.825 ppm to 20 ppm), the dose rates in the feeding study 

correspond to ~0.025x, ~0.075x, and ~0.25x the current maximum reasonable dietary burden 

(MRBD). Based on extrapolation from the highest concentration level (5 ppm) of the feeding 

study with residues at the LOQ (0.01 ppm) in milk, muscle, and fat, HED has concluded that 

tolerances at 0.05 ppm can be established for residues of halosulfuron-methyl in the milk, muscle 
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 23 of 44

and fat of cattle, goats, horses, and sheep based on the reasons stated in the ChemSAC minutes 

(ChemSAC 06/20/2012). The petitioner must propose a tolerance of 0.05 ppm for these 

livestock commodities. If future new use requests increase the dietary burden, a new feeding 

study will be needed.

The available data for liver and kidney are sufficient to assess the existing tolerances for meat 

byproducts. The data indicate that the established tolerances of 0.1 ppm for the meat byproducts 

of cattle, goat, horse, and sheep are too low and should be increased to 1.5 ppm. No change is 

needed for the established tolerance of 0.1 ppm for hog meat byproducts, and tolerances for 

halosulfuron-methyl residues in poultry commodities are not required due to low use rates, low 

residues of halosulfuron-methyl in poultry feed items, and the low transfer rate of residues to 

poultry tissues.

Rotational Crops

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 current 

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

the proposed uses (D394244, J. Meléndez, 5/15/12). 

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
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 24 of 44

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)

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 (DEEM-FCIDTM, Version 2.03), which uses food 

consumption data from the U.S. Department of Agriculture’s Continuing Surveys of Food 

Intakes by Individuals (CSFII) from 1994-1996 and 1998. A conservative dietary exposure 

assessment was performed for halosulfuron methyl. The result of the acute dietary (food and 

drinking water) analysis is below the Agency’s level of concern 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 for the general U.S. population. The acute dietary exposure estimate at the 95th

percentile is <1% of the 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 2.03. A conservative dietary exposure assessment was performed for 

halosulfuron methyl. 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 6% of the cPAD for all 

infants <1 year old, the population subgroup with the highest estimated chronic dietary exposure 

to halosulfuron methyl. 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, no 

cancer risk is expected. 
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 25 of 44

5.4.6 Summary Table

Table 5.4.6. Summary of Dietary Exposures and Risks for Halosulfuron-methyl. 

Population Subgroup

Acute Dietary 

(95th Percentile) Chronic Dietary

Dietary 

Exposure 

(mg/kg/day)

% aPAD

Dietary 

Exposure

(mg/kg/day)

% cPAD

General U.S. Population

N/A N/A

0.002108 2

All Infants (< 1 year old) 0.005726 6

Children 1-2 years old 0.005147 5

Children 3-5 years old 0.004144 4

Children 6-12 years old 0.002642 3

Youth 13-19 years old 0.001674 2

Adults 20-49 years old 0.001733 2

Adults 50+ years old 0.001767 2

Females 13-49 years old 0.003733 <1 0.001726 2

The population subgroup with the highest estimated exposure/risk is bolded.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

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

uses that have been reassessed in this document 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.

The products registered for use on residential turf include water dispersible granule (WG)

formulations. The currently registered EPs available for homeowner use include:

1. Nufarm Prosedge Selective Herbicide (EPA Reg. No. 228-702),

2. Nufarm Prosedge Selective Herbicide (EPA Reg. No. 228-711),

3. Halosulfuron 75WDG Herbicide (EPA Reg. No. 2749-528),

4. GWN-3069 Turf Herbicide (EPA Reg. No. 81880-1),

5. NC-319 75WG T Turf Herbicide (EPA Reg. No. 81880-17),

6. GWN-9843 Turf Herbicide (EPA Reg. No. 81880-23), and

7. GWN-9861 Turf Herbicide (EPA Reg. No. 81880-24).

6.1 Residential Handler Exposure

Residential handler exposure is expected to be short-term. Intermediate-term exposures are not 

likely because of the intermittent nature of applications by homeowners.
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 26 of 44

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

following exposure scenarios:

1. mixing/loading/applying WGs with a manually pressurized handgun,

2. mixing/loading/applying WGs with a hose-end sprayer,

3. mixing/loading/applying WGs with a backpack sprayer, and

4. mixing/loading/applying WGs with a sprinkler can.

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.

6.2 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 assessed include:

1. Physical activities on turf: adults (dermal) and children 1 to < 2 years old (dermal and 

incidental oral);

2. Mowing: adults (dermal) and children 11 to < 16 years old (dermal); and

3. Golfing: adults (dermal), children 11 to < 16 years old (dermal), and children 6 to < 11

years old (dermal).
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 27 of 44

Table 6.2 presents the post-application dermal and incidental oral MOEs calculated after 

applications of halosulfuron-methyl to turf. Post-application risk estimates for all scenarios are 

greater than the LOC of 100 and therefore not of concern (MOEs range from 960 to 11,000,000). 

Table 6.2. Short-Term Residential Post-Application Exposure and Risk Estimates for Halosulfuron-Methyl on Turf.

Lifestage Post-Application Exposure Scenario Dose a

MOE b

mg/kg/day

Water Dispersible Granule (WG) Formulations

max single application rate: 0.14 lb ai/A

Adult

Dermal

Physical Activities on Turf 0.0525 1,900

Mowing 0.00107 93,000

Golfing 0.00412 24,000

Child 11 to < 16 years old Mowing 0.00123 81,000

Golfing 0.00480 21,000

Child 6 to < 11 years old Golfing 0.00568 18,000

Child 1 to < 2 year old

Physical Activities on Turf 0.104 960

Oral

Hand to Mouth 0.00216 23,000

Object to Mouth 0.0000664 750,000

Short-Term Incidental Soil Ingestion 0.00000474 11,000,000

a Dermal Dose = TTR/DFR (μg/cm2) × CF1 (0.001 mg/μg) × TC (cm2/hr) × Exposure Time (hrs) ÷ body weight (kg). TC for 

physical activities on turf: 180,000 cm2/hr for adults and 49,000 cm2/hr for children 1-2 years old. TCs for mowing: 5,500 

cm2/hr for adults and 4,500 cm2/hr for children 11 to < 16 years old. TCs for golfing: 300 cm2/hr for adults, 4,400 cm2/hr for 

children 11 to < 16 years old, and 2,900 cm2/hr for children 6 to < 11 years old. Exposure times for physical activities on turf: 

1.5 hrs for adults and children. Exposure time for mowing: 1 hr. Exposure time for golfing: 4 hrs. Body weight for adult: 80kg. 

Body weight for children 11 to < 16 years old: 57 kg. Body weight for children 6 to < 11 years old: 32 kg. Body weight for 

children 1 to < 2: 11 kg.

Hand-to-Mouth Dose = hand residue loading (mg/cm2) × fraction of hand mouthed (0.127) × surface area of 1 hand (150 cm2) 

× exposure time (1.5 hrs/day) × # of replenishment intervals/hr (4 int/hr) × (1-((1-saliva extraction factor (0.5))^(Number of 

hand-to-mouth events per hour (13.9 events/hr) ÷ # of replenishment intervals/hr)) ÷ body weight (11 kg).

Object-to-Mouth Dose = object residue loading (μg/cm2) × unit conversion factor (0.001 mg/μg) × object surface area mouthed

/ event (10 cm2/event) × exposure time (1.5 hrs/day) × # replenishment intervals/hr (4 int/hr) × (1-((1- saliva extraction factor 

(0.50))^(# Object-to-Mouth Events/hr (8.8 events/hr) ÷ # replenishment intervals/hr)) ÷ body weight (11 kg).

Soil Ingestion = soil residue (μg/g) × ingestion rate (50 mg/day) × conversion factor (0.000001 g/μg) ÷ body weight (11 kg).

b MOE = NOAEL ÷ Daily Dose (mg/kg/day). Dermal NOAEL= 100 mg/kg/day. Level of concern = 100.

6.3 Combined Exposure

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

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

with the exposed population and when 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.
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 28 of 44

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 (see Table 5).

2 Post-application MOE represents high-end incidental oral exposure for the relevant exposure duration (see Table 5).

3 Total MOE = 1 ÷ [(1/Dermal MOE) + (1/Inhalation MOE)]. Dermal NOAEL = 100 mg/kg/day. Inhalation NOAEL = 50 

mg/kg/day.

5 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 Post-application 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 because the chemical is only 

formulated as a WG, has low vapor pressure (<1 x 10-7 mm Hg at 25 oC) and is applied at a low 

rate (0.0625 lb ai/A). However, volatilization of pesticides may be a potential source of postapplication inhalation exposure to individuals nearby to pesticide applications. The Agency 

sought expert advice and input on issues related to volatilization of pesticides from its Federal 

Insecticide, Fungicide, and Rodenticide Act 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. The Agency 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 put into place, 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 the previouslyregistered uses of halosulfuron-methyl. The Agency has been working with the Spray Drift Task 

Force, EPA Regional Offices, and State Lead Agencies for pesticide regulation and other parties 

to develop the best spray drift management practices. The Agency is now requiring interim 

mitigation measures for aerial applications that must be placed on product labels/labeling. The 

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

Force, a membership of U.S. pesticide registrants, and is developing a policy on how to 
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 29 of 44

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

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

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

off-target drift and risk estimates associated with aerial as well as other application types where 

appropriate. 

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 conducted for residential handlers use on turf. This exposure scenario 

is representative of a worse case inhalation (drift) exposure and may be considered protective of 

most outdoor agricultural and commercial post-application inhalation exposure scenarios.

7.0 Aggregate Exposure/Risk Characterization

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

There is potential acute exposure via the diet (food and drinking water). Refer to Section 5.4.3.

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 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 

(females 13-49 yrs old) 100 29,000 NA 1,900 1,800

Child 1 to < 2 years old 100 9,700 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. 396458

Page 30 of 44

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 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-/Intermediate-Term Handler Risk

Occupational handler exposure to halosulfuron-methyl is expected for individuals involved in 

applications to proso millet and pasture/rangeland (mixing, loading, and applying). For the 

proposed uses on proso millet and crop group 17, halosulfuron-methyl may be applied once postemergent to weed growth. Specifically, for use on proso millet, halosulfuron-methyl may only 

be applied up through layby stage (before grain head emergence). For uses on pasture and 

rangeland, halosulfuron-methyl may be applied as a broadcast to established grasses.

Halosulfuron may be applied to proso millet and pasture/rangeland for weed control via 

groundboom or aircraft. The proposed use pattern is summarized in Table 3. Handler exposure 
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 31 of 44

is expected to be short- or intermediate-term based on information provided on the proposed 

label. The label states that all handlers must wear the proper personal protective equipment 

(PPE): a long-sleeved shirt, long pants, chemical-resistant gloves, shoes, and socks.

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

following exposure scenarios: 

1. Mixing/loading dry flowables to support groundboom applications, 

2. Mixing/loading dry flowables to support aerial applications,

3. Flagging to support aerial application,

4. Applying sprays with groundboom equipment, and

5. Applying sprays with aerial equipment.

All handler scenarios result in MOEs greater than the LOC (MOEs ≥ 100) at baseline and do not 

exceed HED’s LOC. For proso millet, the baseline short-term combined (dermal + inhalation) 

MOEs range from 3,000 to 140,000. Intermediate-term exposure is unlikely due to the 

agricultural practices of millet. Proso millet is only grown once per season and its growing 

season is generally less than 100 days. For pasture and rangeland, the baseline short-term 

combined (dermal + inhalation) MOEs range from 15,000 to 71,000 and the baseline 

intermediate-term combined MOEs range from 200 to 9,600. Summaries of the short- and 

intermediate-term risk estimates for occupational handlers are included in Tables 9.1.1-9.1.3. 

The maximum application rate with baseline PPE is presented as the worst case for each 

exposure scenario.
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 32 of 44

Table 9.1.1. Baseline Short-Term Occupational Exposures and Risk Estimates for Halosulfuron-Methyl Use on Proso Millet.

Exposure Scenario

Application 

Rate a

Area 

Treated 

Daily b

Baseline 

Dermal Unit 

Exposures c

Baseline 

Inhalation 

Unit 

Exposures c

Baseline 

Dermal 

Dose d

Baseline 

Inhalation 

Dose d

Baseline 

Short-Term 

Dermal 

MOE e

Baseline 

Short-Term 

Inhalation 

MOE e

Baseline 

Short-Term 

Total

MOE f

lb ai/A acres μg/lb ai μg/lb ai mg/kg/day mg/kg/day LOC = 100 LOC = 100 LOC = 100

Mixer/Loader

Mixing/Loading Dry 

Flowables for Groundboom 

Application

0.03133 80 227 8.96 0.0071 0.00028 14,000 180,000 13,000

Mixing/Loading Dry 

Flowables for Aerial 

Application

0.03133 350 227 8.96 0.0313 0.0012 3,200 41,000 3,000

Flagger

Flagging for

Aerial Application 0.03133 350 11 0.35 0.0015 0.000048 66,000 1,000,000 63,000

Applicator

Applying Sprays via 

Groundboom Equipment 0.03133 80 78.6 0.34 0.0025 0.000011 41,000 4,700,000 40,000

Applying Sprays via

Aerial Equipment * 0.03133 350 5 0.068 0.00068 0.0000093 150,000 5,400,000 140,000

a Application Rates based on proposed uses for halosulfuron-methyl (EPA Reg. No. 81880-2, -6, -18).

b Acres Treated Per Day is taken from Exposure Science Advisory Council (ExpoSAC) Policy No. 9.1.

c Unit Exposures based on PHED Version 1.1 or AHETF data. Baseline = no gloves, no respirator. *Baseline aircraft = engineering controls.

d Dose (mg/kg/day) = daily unit exposure (μg/lb ai) × application rate (lb ai/acre) × amount handled ÷ day (acres/day) × conversion factor (1 mg/1,000 μg) ×

absorption factor (%) / body weight (80 kg). 

e MOE = NOAEL (mg/kg/day) / Dose (mg/kg/day). Level of concern = 100. ST Dermal NOAEL = 100 mg/kg/day. ST Inhalation NOAEL = 50 mg/kg/day.

f Total MOE = 1 / ( (1/Demal MOE) + (1/Inhalation MOE)).
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 33 of 44

Table 9.1.2. Baseline Short-Term Occupational Exposures and Risk Estimates for Halosulfuron-Methyl Use on Crop Group 17 (Grass, Forage, 

Fodder, and Hay).

Exposure Scenario

Application 

Rate a

Area 

Treated 

Daily b

Baseline 

Dermal Unit 

Exposures c

Baseline 

Inhalation 

Unit 

Exposures c

Baseline 

Dermal 

Dose d

Baseline 

Inhalation 

Dose d

Baseline 

Short-Term 

Dermal 

MOE e

Baseline 

Short-Term 

Inhalation 

MOE e

Baseline 

Short-Term 

Total

MOE f

lb ai/A acres μg/lb ai μg/lb ai mg/kg/day mg/kg/day LOC = 100 LOC = 100 LOC = 100

Mixer/Loader

Mixing/Loading Dry 

Flowables for Groundboom 

Application

0.0625 80 227 8.96 0.014 0.00056 7,000 89,000 6,500

Mixing/Loading Dry 

Flowables for Aerial 

Application

0.0625 350 227 8.96 0.062 0.0025 1,600 20,000 1,500

Flagger

Flagging for

Aerial Application 0.0625 350 11 0.35 0.0030 0.000096 33,000 520,000 31,000

Applicator

Applying Sprays via 

Groundboom Equipment 0.0625 80 78.6 0.34 0.0049 0.000021 20,000 2,400,000 20,000

Applying Sprays via

Aerial Equipment * 0.0625 350 5 0.068 0.0014 0.000019 73,000 2,700,000 71,000

a Application Rates based on proposed uses for halosulfuron-methyl (EPA Reg. No. 81880-2, -6, -18).

b Acres Treated Per Day is taken from Exposure Science Advisory Council (ExpoSAC) Policy No. 9.1.

c Unit Exposures based on PHED Version 1.1 or AHETF data. Baseline = no gloves, no respirator. *Baseline aircraft = engineering controls.

d Dose (mg/kg/day) = daily unit exposure (μg/lb ai) × application rate (lb ai/acre) × amount handled ÷ day (acres/day) × conversion factor (1 mg/1,000 μg) ×

absorption factor (%) / body weight (80 kg). 

e MOE = NOAEL (mg/kg/day) / Dose (mg/kg/day). Level of concern = 100. ST Dermal NOAEL = 100 mg/kg/day. ST Inhalation NOAEL = 50 mg/kg/day.

f Total MOE = 1 / ( (1/Demal MOE) + (1/Inhalation MOE)).
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 34 of 44

Table 9.1.3. Baseline Intermediate-Term Occupational Exposures and Risk Estimates for Halosulfuron-Methyl Use on Crop Group 17 (Grass, Forage, 

Fodder, and Hay).

Exposure Scenario

Application 

Rate a

Area 

Treated 

Daily b

Baseline 

Dermal Unit 

Exposures c

Baseline 

Inhalation 

Unit 

Exposures c

Baseline 

Dermal 

Dose d

Baseline 

Inhalation 

Dose d

Baseline 

Int-Term 

Dermal 

MOE e

Baseline 

Int-Term 

Inhalation 

MOE e

Baseline 

Total 

Dose

Baseline IntTerm Total

MOE f

lb ai/A acres μg/lb ai mg/kg/day LOC = 100 mg/kg/day LOC = 100

Mixer/Loader

Mixing/Loading 

Dry Flowables for 

Groundboom 

Application

0.0625 80 227 8.96 0.0106 0.00056 940 18,000 0.0112 890

Mixing/Loading 

Dry Flowables for 

Aerial Application

0.0625 350 227 8.96 0.047 0.0026 210 4,100 0.0490 200

Flagger

Flagging for

Aerial Application 0.0625 350 11 0.35 0.00226 0.000096 4,400 100,000 0.00235 4,300

Applicator

Applying Sprays 

via Groundboom 

Equipment

0.0625 80 78.6 0.34 0.0037 0.000021 2,700 470,000 0.00371 2,700

Applying Sprays 

via

Aerial Equipment *

0.0625 350 5 0.068 0.0010 0.000019 9,800 540,000 0.00104 9,600

a Application Rates based on proposed uses for halosulfuron-methyl (EPA Reg. No. 81880-2, -6, -18).

b Acres Treated Per Day is taken from Exposure Science Advisory Council (ExpoSAC) Policy No. 9.1.

c Unit Exposures based on PHED Version 1.1 or AHETF data. Baseline = no gloves, no respirator. *Baseline aircraft = engineering controls.

d Dose (mg/kg/day) = daily unit exposure (μg/lb ai) × application rate (lb ai/acre) × amount handled ÷ day (acres/day) × conversion factor (1 mg/1,000 μg) ×

absorption factor (%) / body weight (80 kg). Intermediate-term dermal absorption factor = 75%.

e MOE = NOAEL (mg/kg/day) / Dose (mg/kg/day). Level of concern = 100. IT Dermal NOAEL = IT Inhalation NOAEL = 10 mg/kg/day.
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 35 of 44

f Total MOE = NOAEL / (Demal MOE + Inhalation MOE).
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 36 of 44

9.2 Short-/Intermediate-Term Post-Application Risk

Based on the proposed use patterns, post-application exposure to halosulfuron-methyl is 

possible. Agricultural workers performing typical post-application activities (e.g. scouting, hand 

weeding) may receive exposure to halosulfuron-methyl residues. For the proposed uses on proso 

millet and crop group 17, halosulfuron-methyl may be applied once post-emergent to weed 

growth. Specifically, for use on proso millet, halosulfuron-methyl may only be applied up 

through layby stage (before grain head emergence). For uses on pasture and rangeland, 

halosulfuron-methyl may be applied as a broadcast to established grasses.

9.2.1 Dermal Post-Application Risk

HED’s post-application exposure estimates are based on surrogate data. The transfer coefficients 

(TCs) are considered to be central tendency. Maximum application rates were used in this 

assessment. Overall, the post-application risk estimates are characterized as being central to 

high-end estimates. All scenarios resulted in MOEs greater than the LOC of 100 (ranging from 

400 to 160,000) on day 0 (12 hours after application) and, therefore, are not of concern to HED. 

The post-application exposure scenarios are summarized in Table 9.2.1 and 9.2.2.

Table 9.2.1. Short-Term Post-Application Exposures and Risk Estimates for Halosulfuron-Methyl.

Activity Transfer

Coefficient

Days After 

Treatment

DFR a Daily Dermal Dose b Dermal MOE c

μg/cm2 mg/kg/day LOC = 100

Proso Millet

irrigation (hand set) 1,900 0

(12 hours) 0.088 0.0166 6,000

scouting 1,100 0

(12 hours) 0.088 0.0096 10,000

hand weeding 70

0

(12 hours) 0.088 0.00061 160,000

Crop Group 17 (Pasture and Rangeland)

irrigation (hand set) 1,900 0

(12 hours) 0.175 0.0333 3,000

scouting 1,100 0

(12 hours) 0.175 0.0193 5,200

hand weeding 70

0

(12 hours) 0.175 0.00123 82,000

a DFR (μg/cm2) = application rate (0.0313 or 0.0625 lb ai/acre) × fraction of application rate dislodgeable on day 0 (25%) × (1 -

fraction of residue that dissipates daily 10%)t× 4.54E8 μg/lb × 2.47E-8 acre/cm2.

b Short-Term Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day] body weight (80 kg 

adult).

c Short-Term MOE = NOAEL (mg/kg/day) ÷ Daily Dermal Dose (mg/kg/day). ST NOAEL = 100 mg/kg/day. LOC = 100.
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 37 of 44

Table 9.2.2. Intermediate-Term Post-Application Exposures and Risk Estimates for Halosulfuron-Methyl.

Activity Transfer

Coefficient

Days After 

Treatment

DFR a Daily Dermal Dose b Dermal MOE c

μg/cm2 mg/kg/day LOC = 100

Proso Millet

irrigation (hand set) 1,900 0

(12 hours) 0.088 0.0125 800

scouting 1,100 0

(12 hours) 0.088 0.00723 1,400

hand weeding 70

0

(12 hours) 0.088 0.000460 22,000

Crop Group 17 (Pasture and Rangeland)

irrigation (hand set) 1,900 0

(12 hours) 0.175 0.0250 400

scouting 1,100 0

(12 hours) 0.175 0.0145 690

hand weeding 70

0

(12 hours) 0.175 0.000920 11,000

a DFR (μg/cm2) = application rate (0.0313 or 0.0625 lb ai/acre) × fraction of application rate dislodgeable on day 0 (25%) × (1 -

fraction of residue that dissipates daily 10%)t× 4.54E8 μg/lb × 2.47E-8 acre/cm2.

b Intermediate-Term Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal 

absorption 75%] body weight (80 kg adult).

c Intermediate-Term MOE = NOAEL (mg/kg/day) ÷ Daily Dermal Dose (mg/kg/day). IT NOAEL = 10 mg/kg/day. LOC = 100.

Restricted Entry Interval

Typically, under WPS for Agricultural Pesticides, active ingredients classified as acute Toxicity 

Category III or IV for Acute Dermal, Eye Irritation, and Primary Skin Irritation are assigned a 

12-hour REI. Based on the quantitative post-application assessment, the 12-hour REI on the 

proposed label is acceptable.

9.2.2 Inhalation Post-application Risk

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

exposure assessment was not performed 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.
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 38 of 44

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

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., 06/21/2012, DP393948, “Halosulfuron-methyl. Application for Section 3 

Registration of Yukon Herbicide (EPA Reg. No. 81880-6), Sandea Herbicide (EPA Reg. No. 

81880-18), and GWN-3061 Herbicide (EPA Reg. No. 81880-2) to Add New Uses on Proso 

Millet and Pasture and Rangeland Grasses. Summary of Analytical Chemistry and Residue 

Data.”

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., 07/12/2012, DP396460, “Halosulfuron-methyl. Acute and Chronic Aggregate Dietary 

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

Action on Proso Millet and Crop Group 17 (Grass, Forage, Fodder, and Hay).”

Whang, P., 03/01/2012. DP397243. “Halosulfuron-Methyl. Response to a 28-day inhalation 

toxicity study waiver request”.
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 39 of 44

Appendix A. Toxicology Profile 

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) 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

CR

yes

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 ...

870.5xxx Mutagenicity—Structural Chromosomal Aberrations....

870.5xxx 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

CR

yes

yes

-

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

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

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

yes

CR

yes

yes

-

yes
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 40 of 44

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 (Repeated dosing and others).

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.

870.4100 

(83-1b) 

Chronic oral 

toxicity study in 

dogs

42396211 (1991)/ 

Acceptable/Guideline

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

mg/kg/day (capsule).

NOAEL = 10 mg/kg/day

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

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/ 

42661418 (1992)/ 

Acceptable/Guideline

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

LOAEL = M=225.6, F=138.6 mg/kg/day based on 
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 41 of 44

Table A.2.2. Toxicity Profile of Halosulfuron-Methyl Technical (Repeated dosing and others).

Guideline 

No.

Study Type MRID No. 

(Date)/Classification/ Doses

Results

Carcinogenicity in 

rats

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)

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.

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

870.6200a 

(82-7)

Acute 

neurotoxicity in 

45754701 (1994) and 

46199501 (1989)[positive 

NOAEL = 600 mg/kg. 

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

in males. 
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 42 of 44

Table A.2.2. Toxicity Profile of Halosulfuron-Methyl Technical (Repeated dosing and others).

Guideline 

No.

Study Type MRID No. 

(Date)/Classification/ Doses

Results

rats. control study]/ 

Acceptable/Guideline

Doses: 0, 200, 600, or 2000 

mg/kg (limit dose)

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. 

870.6300 

(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.

870.5100 

(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.

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.
Halosulfuron-Methyl Human Health Risk Assessment DP No. 396458

Page 43 of 44

Table A.2.2. Toxicity Profile of Halosulfuron-Methyl Technical (Repeated dosing and others).

Guideline 

No.

Study Type MRID No. 

(Date)/Classification/ Doses

Results

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. 396458

Page 44 of 44

Appendix B. International Residue Limits

Halosulfuron-methyl (128721; 02/29/2012)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR 180.479

Plant: Halosulfuron-methyl, methyl 5-[(4,6-dimethoxy-2-

pyrimidiny)amino]carbonylaminosulfonyl]-3-chloro-1-

methyl-1H-pyrazole-4-carboxylate

Livestock: Halosulfuron-methyl residues containing the 3-

chlorosulfonamide (3-CSA) moiety, expressed as the 

stoichiometric equivalent of halosulfuron-methyl

None None

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

US Canada Mexico2 Codex3

Millet, proso, forage 10

Millet, proso, hay 0.01

Millet, proso, grain 0.01

Millet, proso, straw 0.01

Grass, forage, fodder, and hay, 

group 17, forage

20

Grass, forage, fodder, and hay, 

group 17, hay

0.5

Cattle, meat byproducts 1.0

Goat, meat byproducts 1.0

Horse, meat byproducts 1.0

Sheep, meat byproducts 1.0

Cattle, fat 0.05

Cattle, meat 0.05

Goat, fat 0.05

Goat, meat 0.05

Horse, fat 0.05

Horse, meat 0.05

Milk 0.05

Sheep, fat 0.05

Sheep, meat 0.05

Completed: M. Negussie; 06/21/2012

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.

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.