Page 1 of 47

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

 OFFICE OF

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: April 5, 2010 

MEMORANDUM

SUBJECT: Halosulfuron-Methyl: Human Health Risk Assessment for IR-4 Proposed Uses

on Crop Group 6B Succulent Shelled Pea and Bean Subgroup, Crop Group 1C Tuberous 

and Corn Vegetables Subgroup, Crop Group 6C Dried Shelled Pea and Bean (Except 

Soybean), Subgroup 13-07B Bushberry, Okra, Apples, and Rhubarb.

PC Code: 128721 DP Barcode: D366410

Decision No.: 414896 Registration No.: 81880-18

Petition No.: 9E7577 Regulatory Action: Section 3 

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

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

MRID No.: NA 40 CFR: 180.479

FROM: Whang Phang, Toxicologist, Risk Assessor

Nancy Tsaur, Chemist, ORE Assessor

Risk Assessment Branch 3

Health Effects Division (7509P)

Debra Rate, Biologist, Residue Chemistry and Dietary Assessor

RIMUERB/RD (7505P)

THRU: Paula A. Deschamp, Branch Chief

Risk Assessment Branch 3

Health Effects Division (7509P)

TO: Sidney Jackson/Barbara Madden, RM 05

RIMUERB/Registration Division (7505P)

IR-4 has proposed the establishment of a permanent tolerance for residues of the herbicide 

halosulfuron-methyl [methyl 5-[(4,6-dimethoxy-2-pyrimidinyl)amino] carbonylaminosulfonyl-3-

chloro-1-methyl-1H-pyrazole-4-carboxylate] in/on the following agricultural commodity:

Pea and bean, succulent shelled, Subgroup 6B ...................................0.05 ppm

Vegetable, tuberous and corm, Subgroup 1C ......................................0.05 ppm

Pea and bean, dried shelled, except soybean, Subgroup 6C ................0.05 ppm

Bushberry, Subgroup 13-07B ..............................................................0.05 ppm

Rhubarb ...............................................................................................0.05 ppm
Page 2 of 47

Apple ...................................................................................................0.05 ppm

Okra .....................................................................................................0.05 ppm

The most recent human health risk assessment was conducted for uses on soybean (D358031, W. 

Phang, 6/30/2009). 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 (D331643, M. Rust, 9/21/2006). The details of hazard 

characterization and the rationale for toxicity endpoint selection will not be repeated in this risk 

assessment. However, the salient features will be summarized for these two topics and for the 

Food Quality Protection Act (FQPA) safety factor discussion.

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

registered uses of halosulfuron-methyl are provided in this document and its attachments. The 

residue chemistry data submitted in support of this petition were reviewed by Debra Rate, who 

also conducted the dietary assessment. The occupational/residential assessment was performed 

by Nancy Tsaur. The drinking water assessment was conducted by Michael Barrett of the 

Environmental Fates and Effects Division (EFED). The toxicology evaluation and risk 

assessment were performed by Whang Phang.

Recommendations for Tolerance

Pending submission of a revised Section B, a revised Section F, and reference standards, HED 

concludes that the toxicology and residue chemistry databases, the dietary, residential, aggregate, 

and occupational risk assessments support the requested uses on the following crops and 

establishment of the following tolerances: 

Pea and bean, succulent shelled, Subgroup 6B ...................................0.05 ppm

Vegetable, tuberous and corm, Subgroup 1C ......................................0.05 ppm

Bushberry, Subgroup 13-07B ..............................................................0.05 ppm

Rhubarb ...............................................................................................0.05 ppm

Apple ...................................................................................................0.05 ppm

Okra .....................................................................................................0.05 ppm

At this time, HED is unable to recommend establishment of the proposed tolerance for dried 

shelled bean (except soybean) and pea, Crop Subgroup 6C because data are required for dried 

pea including the forages and hay of field pea cultivars. In addition, concomitant with the 

establishment of a tolerance for Subgroup 6B, the individual tolerance for ‘bean, snap, succulent’ 

should be revoked.
Page 3 of 47

Table of Contents

1.0 EXECUTIVE SUMMARY ................................................................................................ 4

2.0 INGREDIENT PROFILE................................................................................................... 8

2.1 Summary of Proposed Uses.................................................................................... 8

2.3 Physical/Chemical Properties Characterization.................................................... 11

3.0 HAZARD CHARACTERIZATION ................................................................................ 13

3.1 FQPA Safety Factor for Infants and Children ...................................................... 16

3.2 Endocrine Disruption............................................................................................ 17

4.0 DIETARY EXPOSURE/RISK CHARACTERIZATION................................................ 18

4.1 Pesticide Metabolism and Environmental Degradation........................................ 18

4.2 Dietary Exposure and Risk ................................................................................... 26

5.0 RESIDENTIAL (Non-Occupational) EXPOSURE/RISK CHARACTERIZATION...... 27

5.1 Residential Handler Exposure............................................................................... 28

5.2 Residential Postapplication Exposure................................................................... 28

5.3 Other (Spray Drift, etc.)........................................................................................ 29

6.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION.............. 29

6.1 Acute Aggregate Risk........................................................................................... 29

6.2 Short-Term Aggregate Risk.................................................................................. 30

6.3 Intermediate-Term Aggregate Risk ...................................................................... 30

7.0 CUMULATIVE RISK CHARACTERIZATION/ASSESSMENT.................................. 31

8.0 OCCUPATIONAL EXPOSURE/RISK PATHWAY....................................................... 32

8.1 Short- and Intermediate-Term Handler Exposure and Risk ................................. 32

8.2 Postapplication Exposure/Risk ............................................................................. 38

8.2.1 Data and Assumptions for Postapplication Exposure Scenarios .............. 38

8.2.2 Agricultural Post-application Exposure and Risk..................................... 39

9.0 DATA NEEDS/LABEL RECOMMENDATIONS.......................................................... 40

9.1 Toxicology ............................................................................................................ 40

9.2 Residue Chemistry................................................................................................ 40

REFERENCES ............................................................................................................................. 41

Attachment A: Toxicology Profile................................................................................................ 43

Attachment B: Rationale for Requiring the Studies ..................................................................... 46
Page 4 of 47

1.0 EXECUTIVE SUMMARY

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

which inhibits the action of acetolacetate synthase enzyme, a specific plant enzyme. 

Halosulfuron-methyl is used for the pre- and postemergence control of annual broadleaf weeds 

and nutsedges in selected crops, as well as residential turf grass and ornamentals. It is 

formulated as a water dispersible granule (WDG). 

The petitioner, Interregional Research Project No. 4 (IR-4), has proposed new uses of 

halosulfuron-methyl on apple; bushberry Subgroup 13-07B; okra; succulent-shelled pea and bean 

Subgroup 6B; dried shelled pea and bean, except soybean, Subgroup 6C; rhubarb; and tuberous 

and corm vegetable Subgroup 1C. In conjunction with the requested amended use, IR-4 has 

submitted a petition, PP#9E7577, to propose the establishment of permanent tolerances for 

residues of the herbicide halosulfuron-methyl (methyl 3-chloro-5-[[[[(4,6-dimethoxy-2-

pyrimidinyl)amino]carbonyl]amino]sulfonyl]-1-methyl-1H-pyrazole-4-carboxylate) in/on the 

following raw agricultural commodities:

Pea and bean, succulent shelled, Subgroup 6B ...................................0.05 ppm

Vegetable, tuberous and corm, Subgroup 1C ......................................0.05 ppm

Pea and bean, dried shelled, except soybean, Subgroup 6C ................0.05 ppm

Bushberry, Subgroup 13-07B ..............................................................0.05 ppm

Rhubarb ...............................................................................................0.05 ppm

Apple ...................................................................................................0.05 ppm

Okra .....................................................................................................0.05 ppm

HED has conducted a human health risk assessment for halosulfuron-methyl for the purpose of 

establishing the proposed tolerances for uses in or on the above agricultural commodities. In

addition, concomitant with the establishment of a tolerance for Subgroup 6B, the individual 

tolerance for ‘bean, snap, succulent’ should be revoked.

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

halosulfuron-methyl.

Hazard Assessment and Dose-Response Assessment

The toxicology database is adequate to support the current petition for establishing the proposed 

tolerances for uses in/on the above raw agricultural commodities, with the exception of an 

immunotoxicity study required under the new rule in 40 CFR Part 158. This study is required as 

a condition of registration for this action. However, an additional safety factor is not needed to 

account for lack of this study because the current data suggest halosulfuron-methyl does not 

directly target the immune system.

Halosulfuron-methyl has low acute toxicity via the oral, dermal, and inhalation routes. It is a 

non-irritant for skin and eyes and is not a dermal sensitizer. With repeated dosing, halosulfuron 

produces non-specific effects, which are frequently characterized by reduced body weight and 

body weight gains in the test animals. Carcinogenicity studies in rats and mice show no increase 
Page 5 of 47

in treatment-related tumor incidence, and it is classified as “not likely to be carcinogenic to 

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

Although the data indicated an increase in qualitative susceptibility in fetuses following prenatal 

exposure in rats and rabbits, the developmental effects were seen in the presence of maternal 

effects and clear NOAELs and LOAELs were established for both maternal and developmental 

effects. In addition, the developmental effects in rats were seen at doses approaching the limit 

dose (1000 mg/kg). It was concluded that the degree of concern was low and there was no 

residual uncertainty in either the rat or rabbit developmental toxicity study. The FQPA safety 

factor was reduced to 1X.

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 depart is presented in 

Table 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, MOEs and exposures can be 

aggregated where appropriate. The POD and toxicity endpoints for current risk assessment are 

summarized in Table 1. The level of concern (LOC) for residential and occupational exposures 

via dermal and inhalation routes is for an MOE < 100. 

Acute Dietary Exposure Estimates

An acute dietary exposure analysis for halosulfuron-methyl was conducted using tolerance-level 

residues and 100 % crop treated (CT) for all existing and recommended uses. Estimated 

drinking surface water concentrations (EDWCs) from EFED (59.2 ppb based on modeled use on 

rice) were incorporated directly into the exposure analysis. The only population with a 

toxicological endpoint attributable to a single dose of halosulfuron-methyl was females 13-49 

years old. The results of the analysis indicate that acute risk from the dietary exposure to 

halosulfuron-methyl is less than 1% of the acute population adjusted dose (aPAD) for females 

13-49 years old, and therefore does not exceed HED’s LOC.

Chronic Dietary Exposure Estimates

A chronic dietary analysis for halosulfuron-methyl was conducted using tolerance levels and 

100% CT for all existing and recommended uses. The EDWC for surface water from EFED 

(59.2 ppb based on modeled use on rice) was incorporated directly into the exposure analysis. 

The drinking water estimate should be considered highly conservative. The results of the 

analysis indicate that chronic risk from the dietary exposure to halosulfuron-methyl does not 

exceed HED’s LOC for the general U.S. population or any population subgroup. The estimated 

risk for the general U.S. population is 2% of the chronic PAD (cPAD), and the highest exposure 

is to all infants (<1 year old) at 5% of the cPAD.

Drinking Water Assessment

Halosulfuron-methyl is a mobile and persistent compound which may reach ground and surface 

waters, including those used as drinking water sources. The EDWCs for halosulfuron-methyl are 

based on a maximum annual application rate of 0.125 lb ai/A for rice. The two screening 

models, FIRST and SCI-GROW, were used for estimating EDWCs of halosulfuron-methyl. 

Estimates for halosulfuron-methyl in surface water based on the FIRST model results for rice are 
Page 6 of 47

59.2 ppb for acute and chronic concentrations. It should be noted that the drinking water 

estimate based on rice application is an upper bound estimate. The estimate for halosulfuronmethyl in ground water based on the SCI-GROW model result is 0.065 ppb.

Residential Exposure Estimates

No residential uses are being requested in this petition; however, halosulfuron-methyl is 

currently registered for use on residential turf grass and ornamentals. Short-term exposures may

occur during adult residential handling activities. Short- and intermediate-term exposures may

occur during postapplication activities for adults and children. Combined MOEs for adult and 

children’s dermal exposure and toddler’s incidental oral exposure from all residential activities 

are greater than the LOC of 100, and therefore are not of concern.

Acute Aggregate Risk

For acute aggregate risk, drinking water estimates were incorporated directly into the dietary

analysis for female 13-49 years old. Exposure through food and drinking water sources occupies 

less than 1% of the aPAD; thus, estimated risk does not exceed HED’s level of concern. 

Short-Term Aggregate Risk

The short-term aggregate risk assessment estimates risks likely to result from exposure to 

halosulfuron-methyl residues from food, drinking water, and residential pesticide uses. High-end 

estimates of residential exposure are used, while average values are used for food and drinking 

water exposure (i.e., chronic exposures). Short-term aggregate MOEs range from 2,800 to 4,800. 

The MOE for the U.S. Population is 4,700. The most highly exposed subgroup is All Infants 

(less than 1 year old), with a MOE of 2,800. These estimates of short-term aggregate risk do not 

exceed HED’s level of concern.

Intermediate-Term Aggregate Risk

The intermediate-term aggregate risk assessment estimates risks likely to result from exposure to 

halosulfuron-methyl residues from food, drinking water, and residential pesticide uses. Although 

unlikely due to the use pattern (no more than 4 applications to turf per season), residential 

exposure was included in the intermediate-term aggregate risk assessment. High-end estimates 

of residential exposure are used, while average values are used for food and drinking water 

exposure (i.e., chronic exposures). Intermediate-term aggregate MOEs ranged from 500 to 680. 

The MOE for the U.S. Population is 500. The most highly exposed children’s subgroup was All 

Infants (less than 1 year old), with a MOE of 680. These estimates of aggregate risk do not 

exceed HED’s level of concern.

Occupational Exposure and Risk

For occupational handlers, short- and intermediate-term exposure may occur during mixing, 

loading and application. For occupational postapplication activities, exposure may occur over 

short- and intermediate-term periods. Chronic exposure (6 months of continuous exposure) is 

not expected. 

Agricultural Handler Risk

No chemical-specific handler exposure data were submitted in support of this registration. It is 

the policy of the HED to use data from the Pesticide Handlers Exposure Database (PHED),

Version 1.1 as presented in PHED Surrogate Exposure Guide (8/98) to assess handler exposures 
Page 7 of 47

for regulatory actions when chemical-specific monitoring data are not available (HED ExpoSAC 

Standard Operating Procedure (SOP) No. 7, dated 1/28/99). Data from the Outdoor Residential 

Exposure Task Force (ORETF) are also used when appropriate.

All handler scenarios resulted in MOEs greater than the LOC (MOEs ≥ 100) at some level of risk 

mitigation. The inhalation risk estimates to handlers do not exceed HED’s LOC at baseline (no 

respirator) for any of the handler scenarios where baseline data are available. The combined 

dermal and inhalation risks to handlers do not exceed HED’s LOC with baseline attire (i.e., longsleeved shirt, long pants, shoes, and socks) where baseline data are available. There are no data 

to assess the mixing/loading/applying handgun scenario at baseline attire. The short- and 

intermediate-term combined dermal and inhalation risks do not exceed HED’s LOC for 

mixing/loading/applying with handgun equipment when baseline attire plus chemical-resistant 

gloves are used. 

Agricultural Postapplication Risk

No chemical-specific dislodgeable foliar residue (DFR) data are available for halosulfuronmethyl to assess postapplication dermal risks. Using the default assumption that 20% of the 

application rate is retained on foliage on day 0 yields the dermal MOEs for occupational 

postapplication workers on the day of application greater than 100, demonstrating that there are 

minimal potential risks to workers re-entering fields treated with postemergent applications of 

halosulfuron-methyl. Based on the use pattern, as well as the acute toxicity of halosulfuronmethyl, the 12-hour restricted entry interval (REI) appearing on the label is adequate. 

Recommendations for Tolerance

Pending submission of a revised Section B, a revised Section F, and analytical reference 

standards, there are no additional residue chemistry issues that would preclude granting a Section 

3 registration for the requested uses or the establishment of a tolerance for residues of the 

herbicide halosulfuron-methyl, methyl 3-chloro-5-[[[[(4,6-dimethoxy-2-pyrimidinyl)

amino]carbonyl]amino]sulfonyl]-1-methyl-1H-pyrazole-4-carboxylate, as follows:

Pea and bean, succulent shelled, Subgroup 6B ...................................0.05 ppm

Vegetable, tuberous and corm, Subgroup 1C ......................................0.05 ppm

Bushberry, Subgroup 13-07B ..............................................................0.05 ppm

Rhubarb ...............................................................................................0.05 ppm

Apple ...................................................................................................0.05 ppm

Okra .....................................................................................................0.05 ppm

At this time, HED is unable to recommend for a registration and tolerance for dried shelled bean 

(except soybean) and pea, Crop Subgroup 6C because data are required for dried pea including 

the forages and hay of field pea cultivars. In addition, concomitant with the establishment of a 

tolerance for Subgroup 6B, the individual tolerance for ‘bean, snap, succulent’ should be 

revoked.

Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These studies, which comprise the PHED, 
Page 8 of 47

the Outdoor Residential Exposure Task Force (ORETF), and the Agricultural Reentry Task 

Force (ARTF) have been determined to require a review of their ethical conduct, and have 

received that review.

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.

2.0 INGREDIENT PROFILE

2.1 Summary of Proposed Uses

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 

Sandea® Herbicide (EPA Reg. No. 81880-18) and GWN-3061 Herbicide (EPA Reg. No. 81880-

2). Both products are currently registered to Gowan Company and are classified as WDG

formulations containing 75% halosulfuron-methyl. 

The petitioner, IR-4, is proposing to add the following crops to the Sandea® Herbicide label: 

apple, bushberry Subgroup 13-07B, okra, succulent shelled pea and bean Subgroup 6B, dried 

shelled pea and bean (except soybean) Subgroup 6C, rhubarb, and tuberous and corm vegetables 

Subgroup 1C and also to amend the product label for GWN-3061 Herbicide include uses on 

dried shelled pea and bean (except soybean) Subgroup 6C. The proposed use patterns are 

presented in Table 2.1.
Page 9 of 47

Table 2.1. Proposed Use Pattern for Halosulfuron-Methyl.

Crop

Treatment 

Type/Target 

of 

Application

Application 

Equipment

Maximum 

Application 

Rate

(lb ai/A)

Treatment 

Interval

Preharvest 

Interval

Sandea® Herbicide, EPA Reg. No. 81880-18, WDG 75% ai

Succulent shelled peas and beans 

(subgroup 6B) Ground Groundboom 0.023 lb ai/acre Not applicable Not provided

Tuberous and corm vegetables 

(subgroup 1C)

Ground & 

Foliage Groundboom 0.047 lb ai/acre Not provided 45 days

Rhubarb Ground Groundboom, 

Handgun

0.047 lb 

ai/acre Not applicable 60 days

Bushberry (subgroup 13-07B) Ground & 

Foliage

Groundboom, 

Handgun

0.047 lb 

ai/acre 45 days 14 days

Dried shelled peas and beans 

(except soybean, subgroup 6C)

(West of Rockies)

Ground & 

Foliage

Groundboom, 

Handgun

0.047 lb 

ai/acre Not applicable 30 days

Dried shelled peas and beans 

(except soybean, subgroup 6C)

(East of Rockies)

Ground & 

Foliage

Groundboom, 

Handgun

0.031 lb 

ai/acre Not applicable 30 days

Apples

(West of Rockies) Ground Groundboom, Handgun

0.094 lb 

ai/acre Not provided 14 days

Apples

(East of Rockies) Ground Groundboom, Handgun

0.047 lb 

ai/acre Not provided 14 days

Okra Ground Groundboom, 

Handgun

0.047 lb 

ai/acre Not applicable 30 days

2.2 Directions for Use

The directions for use of halosulfuron-methyl are summarized in Table 2.2. The submitted labels 

for Sandea® Herbicide (EPA Reg. No. 81880-18) and GWN-3061 Herbicide (EPA Reg. No. 

81880-2) are adequate to allow evaluation of the residue data relative to the proposed uses. 

However, the petitioner is required to: (1) amend the proposed use directions of Sandea® 

Herbicide (EPA Reg. No. 81880-18) on Crop Subgroup 6B to prohibit applications to legumes 

grown for livestock feeds because no residue data are available for cowpea forage and hay; (2)

amend the proposed use directions of Sandea® Herbicide (EPA Reg. No. 81880-18) on Crop 

Subgroup 13-07B (bushberry) to remove the instructions pertaining to the use of a non-ionic 

surfactant; and (3) remove the use directions from both labels for Crop Subgroup 6C (dried pea 

and bean (except soybean)). 
Page 10 of 47

Table 2.2. Summary of Directions for Use of Halosulfuron-Methyl.

Applic. Timing, 

Type, and 

Equip.

Formulation

[EPA Reg. 

No.]

Applic. 

Rate 

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Apple; East of the Rocky Mts.

Broadcast to 

orchard floor; 

Ground

(≥15 gal/A)

75% WDG

[81880-18]

0.023-

0.047

Not 

specified

(NS)

0.094 14

Single or sequential 

applications may be made 

on each side of the tree 

row. Use of a non-ionic 

surfactant (NIS) is 

recommended. 

Application to trees 

established less than one 

year is prohibited.

Apple; West of the Rocky Mts.

Broadcast to 

orchard floor; 

Ground

(≥15 gal/A)

75% WDG

[81880-18]

0.035-

0.094 NS 0.094 14

Single or sequential 

applications may be made 

on each side of the tree 

row. Use of an NIS or a 

penetrating type surfactant 

is recommended. 

Application to trees 

established less than one 

year is prohibited.

Bushberry Subgroup 13-07B

Soil broadcast; 

Ground

(≥15 gal/A)

75% WDG

[81880-18]

0.023-

0.047 NS 0.094 14

Single or sequential 

applications may be made 

on each side of the row

with a minimum 

retreatment interval (RTI) 

of 45 days for sequential 

applications. Use of an 

NIS is recommended. 

Application to plants 

established less than one 

year is prohibited.

Fruiting Vegetables Group Including But Not Limited to Eggplant, Okra, Pepper, and Tomato

Row

middle/furrow

applications; 

Ground

(≥15 gal/A; ≥20 

gal/A for okra 

from Section B)

75% WDG

[81880-18]

0.023-

0.047 NS 0.094 30

Applications are to be 

made between rows of 

direct-seeded or 

transplanted fruiting 

vegetables.

Pea and Bean, Succulent Shelled, Subgroup 6B 1

[Any succulent shelled cultivar of bean (Phaseolus, spp.), or immature soybean seed (Glycine max), or any Vigna 

spp., and garden pea (Pisum, spp.)] 

Preemergence;

Soil broadcast; 

Ground

(≥15 gal/A)

75% WDG

[81880-18] 0.023 1 0.023 30

Timing is after planting 

but before crop 

emergence.
Page 11 of 47

Table 2.2. Summary of Directions for Use of Halosulfuron-Methyl.

Applic. Timing, 

Type, and 

Equip.

Formulation

[EPA Reg. 

No.]

Applic. 

Rate 

(lb ai/A)

Max. No. 

Applic. per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Pea and Bean (Except Soybean), Dried Shelled, Subgroup 6C 1; East of the Rocky Mts.

Postemergence;

Broadcast or 

directed; 

Ground

(≥15 gal/A)

75% WDG

[81880-2]

[81880-18]

0.023-

0.031 1

0.047 (per crop 

cycle)

0.094 (per year)

30

Application is to be made 

when plants have 2 to 4 

trifoliate leaves, but 

before flowering. An NIS 

is to be used. Directed 

sprays are recommended.

Pea and Bean (Except Soybean), Dried Shelled, Subgroup 6C; West of the Rocky Mts.

Postemergence;

Broadcast; 

Ground

(≥15 gal/A)

75% WDG

[81880-2]

[81880-18]

0.023-

0.047 1

0.047 (per crop 

cycle)

0.094 (per year)

30

Application is to be made 

when plants have 2 to 4 

trifoliate leaves, but 

before flowering. An NIS 

is to be used. Directed 

sprays are recommended.

Rhubarb

Dormant;

Broadcast; 

Ground

(≥15 gal/A)

75% WDG

[81880-18]

0.023-

0.047 1 0.047 60

Application is to be made 

as close as possible to 

breaking of dormancy. 

An NIS is to be used if 

labeled weeds have 

emerged.

Tuberous and Corm Vegetables, Subgroup 1C

[Arracacha; arrowroot; artichoke, Chinese; artichoke, Jerusalem; canna, edible; cassava, bitter and sweet; chayote 

(root); chufa; dasheen (taro); ginger; leren; potato; sweet potato; tanier; turmeric; yam bean; yam, true]

Preemergence; 

Soil broadcast; 

Ground

(≥15 gal/A)

75% WDG

[81880-18]

0.023-

0.047 2 0.047 45

First application is to be 

made after planting but 

prior to crop emergence; 

if necessary, a second 

application may be made 

45 days before harvest. If 

a second application is 

made, an NIS should be 

used in the second 

application.

Postemergence

Foliar broadcast

Ground

(≥15 gal/A)

1 Individual crop uses of Sandea® Herbicide (EPA Reg. No. 81880-18) are currently registered on succulent beans 

and dry beans; the petitioner now requests uses on Subgroups 6B and 6C. The EP, GWN-3061 Herbicide (EPA 

Reg. No. 81880-2), is also currently registered on soybeans.

2.3 Physical/Chemical Properties Characterization 

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

moiety (3-CSA) are presented in Table 2.3.1. The physicochemical properties of the technical 

grade of halosulfuron-methyl are presented in Table 2.3.2. 
Page 12 of 47

Table 2.3.1. Halosulfuron-Methyl Nomenclature. 

Chemical structure

N

N

CH3

Cl

N

N N

H

N

H

O

S

O

O

O

CH3

O

CH3

O

O

CH3

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)

N

N

CH3

Cl

NH2

S

O

O

OH

O

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

Rearrangement ester (RRE) of 

halosulfuron-methyl

N

N

O

CH3

O

CH3

N

H

N

N

CH3

Cl

O

O

CH3

Table 2.3.2. 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
Page 13 of 47

3.0 HAZARD CHARACTERIZATION

A detailed hazard characterization for halosulfuron-methyl is presented in a risk assessment 

conducted in 2006 (DP331643, M. Rust, et al., 9/21/06). Briefly, the toxicology database for 

halosulfuron-methyl is sufficient and of good quality. However, recent changes to 40 CFR §158 

make the immunotoxicity study (OPPTS Guideline 870.7800) required 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 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.

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 tracts. 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

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. The 

results of both acute and subchronic neurotoxicity studies showed no neurotoxic effects. There 

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

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
Page 14 of 47

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

Halosulfuron-methyl 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. Cancer 

risk assessment will not be conducted for halosulfuron methyl..

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

assessment are summarized in Tables 3.1 (Non-Occupational) and 3.2 (Occupational).

Table 3.1. Toxicological Doses and Endpoints for Halosulfuron-Methyl for Non-Occupational Human Health 

Risk Assessments.

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

(Females 13-49

years of age)

NOAEL= 

50

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF= 1x

Acute RfD = 0.5 

mg/kg/day

aPAD =0.5 

mg/kg/day

Developmental Toxicity - Rabbit

LOAEL = 150 mg/kg/day based on decreased 

mean litter size, increased number of 

resorptions (total and per dam) and increased 

postimplantation loss (developmental 

toxicity).

Acute Dietary 

(General 

Population 

including Infants 

and Children)

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).
Page 15 of 47

Table 3.1. Toxicological Doses and Endpoints for Halosulfuron-Methyl for Non-Occupational Human Health 

Risk Assessments.

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

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 LOC 

for MOE = 100

21-Day Dermal Toxicity Study - Rat

LOAEL = 1000 mg/kg/day based on 

decreased body weight gain in males.

Dermal 

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.

Inhalation 

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).

Inhalation 

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.

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.
Page 16 of 47

Table 3.2. Summary of Toxicological Doses and Endpoints for Halosulfuron-Methyl for Occupational Human 

Health Risk Assessments.

Exposure/

Scenario

Point of 

Departure

(mg/kg/day)

Uncertainty 

Factors

Level of Concern 

for Risk 

Assessment

Study and Toxicological Effects

Dermal ShortTerm (1-30 

days)

NOAEL= 

100 

UFA= 10x

UFH= 10x

Occupational LOC 

for MOE = 100

21-Day Dermal Toxicity Study - Rat

LOAEL = 1000 mg/kg/day based on 

decreased body weight gain in males.

Dermal 

IntermediateTerm (1-6 

months)+

NOAEL=10 UFA= 10x

UFH= 10x

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 UFA= 10x

UFH= 10x

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 

UFA= 10x

UFH= 10x

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 (intra-species). UFH = potential variation in sensitivity among 

members of the human population (inter-species). MOE = margin of exposure. LOC = level of concern. 

3.1 FQPA Safety Factor for Infants and Children

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 a new 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. The decision is based on the following findings:

1. The adequacy of the halosulfuron-methyl data has been described in Section 3.0. 

To reiterate, the toxicity database for halosulfuron-methyl is complete for FQPA 

safety evaluation and toxicity endpoint and points of departure evaluation.

However, under the new rule for registration an immunotoxicity study is required. 

After analysis of the database, an additional factor (UFDB) for database 
Page 17 of 47

uncertainty is not needed to account for the lack of this study because the 

available data do not suggest that this chemical affects the immune system.

2. There is no evidence of increased susceptibility of young rats in the reproduction 

study with halosulfuron-methyl. Although there is qualitative evidence of 

increased susceptibility in the prenatal developmental studies in rats and rabbits, 

the risk assessment team did not identify any residual uncertainties after 

establishing toxicity endpoints and uncertainty factors to be used in the risk 

assessment of halosulfuron-methyl. The degree of concern for pre-and/or postnatal toxicity is low and there are no residual uncertainties.

3. There is no indication in the toxicity data which include acute and subchronic 

neurotoxicity studies that halosulfuron-methyl is a neurotoxic chemical, and there 

is no need for a developmental neurotoxicity study or additional factors (UFs) to 

account for neurotoxicity.

4. There are no residual uncertainties identified in the exposure databases. The 

dietary food exposure assessments were performed based on 100% CT and 

tolerance-level residues, and conservative (protective) assumptions in the ground 

water and surface water modeling were used to assess exposure to halosulfuronmethyl in drinking water. Similarly conservative assumptions were also used to 

assess post-application exposure of children as well as incidental oral exposure of 

toddlers. These assessments will not underestimate the exposure and risks posed 

by halosulfuron-methyl.

3.2 Endocrine Disruption

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (EDSP) to determine whether certain substances (including pesticide active 

and other ingredients) may have an effect in humans or wildlife similar to an effect produced by

a “naturally occurring estrogen, or other such endocrine effects as the Administrator may

designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

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

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine related effects caused by the substance, and 

establish a quantitative relationship between the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first 

group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. 

This list of chemicals was selected based on the potential for human exposure through pathways 

such as food and water, residential activity, and certain post-application agricultural scenarios. 

This list should not be construed as a list of known or likely endocrine disruptors.
Page 18 of 47

Halosulfuron-methyl is not among the group of 58 pesticide active ingredients on the initial list 

to be screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide 

chemicals. Accordingly, EPA anticipates issuing future EDSP orders/data call-ins for all 

Registration Review cases, including those for which EPA has already opened a Registration 

Review docket for a pesticide active ingredient. 

For further information on the status of the EDSP, the policies and procedures, the list of 67 

chemicals, the test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/.

4.0 DIETARY EXPOSURE/RISK CHARACTERIZATION

4.1 Pesticide Metabolism and Environmental Degradation

Nature of the Residue - Plants

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

studies reflecting pre- and postemergence modes of applications on corn, sugarcane, and 

soybean. The metabolism of halosulfuron-methyl was similar in the three tested crops but 

dependent on the mode of application. When halosulfuron-methyl was applied preemergence, 

initial breakdown of the herbicide in the soil and preferential uptake of the pyrazole moieties 

resulted in the primary residue being 3-chlorosulfonamide (3-CSA), which has been determined 

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

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

the major residue was 3-CSA. 

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

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

concluded that the residue of concern in plants is the parent compound, halosulfuron-methyl.

Nature of the Residue - Livestock

Acceptable livestock metabolism studies conducted on goats and hens were previously submitted 

in conjunction with petitions for uses on corn and sorghum. In goat milk and tissues, the major 

extractable residue was the parent; acid hydrolysis released bound or conjugated residues of 

aminopyrimidine and 3-CSA. HED has concluded that the residue of concern in ruminants is 

halosulfuron-methyl; however, because the approved enforcement method for livestock 

commodities quantifies the parent compound and metabolites containing the 3-CSA moiety by

converting residues to 3-CSA, tolerances for residues in livestock commodities are expressed in 

terms of halosulfuron-methyl and its metabolites determined as 3-CSA, expressed as 

halosulfuron-methyl equivalents. 

There are no poultry feedstuffs associated with the recommended tolerances and crop uses

addressed in this action. In addition, Due to low use rates, low residue levels of 

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

tolerances for halosulfuron-methyl residues in poultry commodities are not required (PP# 
Page 19 of 47

2G4073, G. J. Herndon, 3/8/94). Therefore, a discussion of the metabolism of halosulfuronmethyl in poultry is not needed in this action.

Residue Analytical Methods

Plants: The residue analytical methods data are adequate to satisfy data requirements for the 

subject action. An acceptable residue analytical method (GC) is available for tolerance 

enforcement purposes for residues in/on crop commodities (i.e., Monsanto Analytical Method 

RES-109-97-4 (MRID 44495801)). Residues of halosulfuron-methyl in/on the crop 

commodities from the magnitude of the residue studies were determined using an acceptable data 

collection method. Residue in plants were analyzed as the RRE of halosulfuron-methyl (structure 

is shown in Table 2.3.1).

Livestock: An adequate analytical method is available for enforcement of tolerances for 

secondary residues of halosulfuron-methyl in livestock commodities. The method (GC) has been 

validated as an enforcement method by the Analytical Chemistry Branch (ACB)/BEAD at a limit 

of quantification of 0.01 ppm in milk and liver (D. Swineford, 4/28/95).

Multiresidue Methods

Adequate multiresidue method data for halosulfuron-methyl and 3-CSA were submitted 

previously in conjunction with PP#3F4193 (D189198, G.J. Herndon, 3/8/94). Residues of 

halosulfuron-methyl and 3-CSA are not recoverable by the FDA Multiresidue Protocols A 

through E. The results have been forwarded to FDA. 

Additional Reference Standards

As indicated in the most recent risk assessment (D358031, W. Phang, 6/30/09), the registrant 

must submit analytical reference standards for the 3-CSA (3-chlorosulfonamide acid) metabolite 

and the rearrangement ester (RRE) of halosulfuron-methyl to the EPA National Pesticide 

Standards Repository.

Storage Stability

Adequate storage stability data are available to support the storage conditions and durations of 

samples collected from the magnitude of the residue and processing studies on apples, blueberry, 

dry bean seed, succulent pea seed, potato tuber, potato processed commodities, and rhubarb. As 

residues of halosulfuron-methyl have been found to be stable in tested crop matrices, which are

representative of the currently proposed crops proposed crops, storage stability corrections need 

not be applied to the recommended tolerances for halosulfuron-methyl residues in this action. 

Meat, Milk, Poultry, and Eggs

The livestock feedstuffs derived from registered and proposed uses would not significantly 

increase the dietary burdens of halosulfuron-methyl to beef and dairy cattle provided the 

petitioner amends the proposed use directions of Sandea® Herbicide on Crop Subgroup 6B to 

prohibit applications to legumes grown for livestock feeds. The available dairy cattle feeding 

study is adequate, and HED concludes that tolerances for halosulfuron-methyl residues of 

concern need not be established for the milk, meat, and fat of cattle, goat, hog, horse, and sheep. 

The established tolerances of 0.1 ppm for the meat byproducts of cattle, goat, hog, horse, and 

sheep remain adequate. There are no poultry and swine feedstuffs associated with the 
Page 20 of 47

recommended tolerances and crop uses. The petitioner should note that if additional uses are 

proposed in the future which would result in an increase in the dietary burdens, HED will reassess the adequacy of established animal tolerances.

Crop Field Trials

IR-4 has submitted magnitude of the residue studies on apples, blueberry, dry bean, succulent 

pea, potato, and rhubarb. The results from these field trials are discussed below and the residue 

data are summarized in Table 4.1.2.

Table 4.1.2. Summary of Residue Data from Crop Field Trials with Halosulfuron-Methyl.

Crop Matrix Total Applic. 

Rate

(lb ai/A)

PHI 

(days)

Residues of Halosulfuron-methyl (ppm)

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

Apple

(proposed use = 0.094 lb ai/A total application rate, 14-day PHI)

Apple (fruit) 0.092-0.104 13-14 26 <0.05a<0.05 <0.05 0.05 0.05 --

Bushberry Subgroup 13-07B

(proposed use = 0.094 lb ai/A total application rate, 14-day PHI)

Blueberry (fruit) 0.093-0.099 13-14 12 <0.05 <0.05 <0.05 0.05 0.05 --

Okra

(proposed use = 0.094 lb ai/A total application rate, 30-day PHI)

Okra No okra data were submitted.

Pea and Bean, Succulent Shelled, Subgroup 6B

(proposed use = 0.023 lb ai/A total application rate, 30-day PHI)

Pea seed 0.032 55-68 4 <0.05 <0.05 <0.05 0.05 0.05 --

0.060-0.070 55-72; 

1662

18 <0.05 <0.05 <0.05 0.05 0.05 --

Pea seed in pods 0.065-0.066 69-77 6 <0.05 <0.05 <0.05 0.05 0.05 --

Pea and Bean (Except Soybean), Dried Shelled, Subgroup 6C

(proposed use = 0.047 lb ai/A total application rate per crop cycle and 0.094 lb ai/A total application rate per year, 

30-day PHI)

Dry bean seed 0.061-0.075 27-31 24 <0.05 <0.05 <0.05 0.05 0.05 --

Rhubarb

(proposed use = 0.047 lb ai/A total application rate, 60-day PHI)

Rhubarb petiole 0.093-0.101 61-78 8 <0.05 <0.05 <0.05 0.05 0.05 --

Tuberous and Corm Vegetables, Subgroup 1C

(proposed use = 0.047 lb ai/A total application rate, 45-day PHI)

Potato tuber 0.094-0.103 42-46 28 <0.05 <0.05 <0.05 0.05 0.05 --

a

LOQ = 0.05 ppm

Apple

The submitted field trial data for halosulfuron-methyl on apples are adequate with regard to the 

number (13) and locations (6 regions) of field trials. The application rate and PHI reflect the 

proposed use pattern, and the data are supported by concurrent storage stability data. Although 

the apple data did not reflect the use of a nonionic surfactant as recommended on the proposed 

label, this is not an issue as the application is directed to the orchard floor and presence/absence 

of surfactant is not expected to change the residue level on the apple fruit. The available data 

will support the proposed tolerance of 0.05 ppm for apple. 
Page 21 of 47

Bushberry Subgroup 13-07B

The submitted field trial data for halosulfuron-methyl on blueberries and the representative 

commodity of Crop Subgroup 13-07B are adequate with regards to the number and location of 

field trials. The number of field trials is a 25% reduction of the OPPTS 860.1500 guidance; this 

number is considered sufficient to support the Subgroup 13-07B tolerance based on the lack of 

quantifiable residues. The application rate and PHI reflect the proposed use pattern, and the data 

are supported by concurrent storage stability data. However, the blueberry data did not reflect 

the use of a nonionic surfactant as recommended on the proposed label. The blueberry data 

support the proposed tolerance of 0.05 ppm for the bushberry Subgroup 13-07B provided the 

label for Sandea® Herbicide is amended to remove the instructions pertaining to the use of a 

non-ionic surfactant on crops belonging to the Subgroup 13-07B. If it is IR-4’s intention to add a 

nonionic surfactant when Sandea® Herbicide is applied on Subgroup 13-07B, then additional 

field trial data are required. Although the spray is directed to the rows between blueberry

bushes, there is a finite possibility of the spray contacting the bushes, and the presence/absence 

of surfactant might impact the residue on the blueberries.

 

Okra

No residue data were submitted to support the proposed use on okra. Okra was listed by the 

petitioner in its proposed labels as part of the fruiting vegetables crop group. The ChemSAC 

meeting of 10/18/2006 has recommended the inclusion of okra in Crop Group 8 (fruiting 

vegetables). The ChemSAC has also determined that a separate tolerance for okra should be 

listed in the appropriate section of the CFR entry until the new crop group regulation is 

published.

A tolerance of 0.05 ppm for residues of halosulfuron-methyl has been established on the fruiting 

vegetable Crop Group 8 based on field trial data for tomato and pepper (D267423, A. Acierto, 

4/25/2002). The available field trial data for fruiting vegetables will be translated to okra. HED

recommends for the establishment of a tolerance of 0.05 ppm for residues of halosulfuron-methyl 

in/on okra. This recommendation is identical to the level proposed by the petitioner.

Pea and Bean, Succulent Shelled, Subgroup 6B

The representative crops of Subgroup 6B are any succulent shelled cultivar of bean (Phaseolus

spp.) and garden pea (Pisum spp.). IR-4 has submitted field trial data for halosulfuron-methyl on 

succulent shelled and edible podded peas from 12 field trials conducted in the United States 

during the 2003-2004 growing seasons. The field trial data for succulent peas do not fully

support the proposed use pattern because the trials were conducted at exaggerated rates (1.4X or 

2.8X) and the collected samples did not reflect the proposed 30-day PHI (the earliest PHI tested 

was 55 days). The available data for succulent beans, previously submitted under PP#1E06322 

(D278587, A. Acierto, 6/15/2002) to support the established individual tolerance of 0.05 ppm, 

also do not reflect the proposed use on Subgroup 6B because these data represent foliar 

application whereas the new proposed use pattern is for preemergence soil application. 

HED will not require additional data on succulent peas since treatment at 1X will likely result in 

residues below 0.05 ppm, even when harvested at a PHI of 30-days. HED also will not require 

additional data on succulent beans since soil treatment will likely result in residues below 0.05 

ppm. HED recommends for the proposed tolerance of 0.05 ppm for the Subgroup 6B (pea and 
Page 22 of 47

bean, succulent shelled). Concomitant with the establishment of a tolerance for Subgroup 6B, 

the individual tolerance for ‘bean, snap, succulent’ should be revoked.

Pea and Bean (Except Soybean), Dried Shelled, Subgroup 6C

The representative commodities of Subgroup 6C are any one dried cultivar of bean (Phaseolus

spp.) and any one dried cultivar of pea (Pisum spp.) The submitted residue data for dry bean are 

adequate with regard to geographic representation of data; the data are supported by concurrent 

storage stability data. The dry bean data from the current submission reflect a single foliar 

broadcast application conducted at ~1.6X the proposed application rate per crop cycle (or ~0.8X

the proposed total application rate per year), the use of a nonionic surfactant, and an approximate 

30-day PHI. Additional data for dry beans were submitted under PP#1E06322 (DP#278587, A. 

Acierto, 6/15/2002) to support the established individual tolerance of 0.05 ppm. These data 

represent a single application of Permit 75 WDG Herbicide at 0.032 lb ai/A made 0 to 6 days 

after planting and a 86- to 113-day PHI.

HED is unable to recommend for the proposed tolerance of 0.05 ppm for Crop Subgroup 6C 

(Dried Shelled Bean (Except Soybean) and Pea) at this time because residue data on dried pea 

including the forages and hay of field pea cultivars are required. When adequate residue data for 

dried peas become available, the petitioner may again request a tolerance for Subgroup 6C. A 

revised Section F should be submitted removing the request for Crop Subgroup 6C (dried shelled 

pea and bean (except soybean)).

Rhubarb

The submitted field trial data for halosulfuron-methyl on rhubarb are adequate with regard to the 

number and location of field trials. The data also reflected the use of nonionic surfactant as 

recommended on the proposed label, samples were collected at appropriate PHI, and were 

supported by concurrent storage stability data. However, the rhubarb data were generated using 

slightly exaggerated rates of ~2.0-2.1X. At this time, HED does not require additional data on 

rhubarb since treatment at 1X is likely to yield residues below 0.05 ppm. The available data are 

supportive of the proposed tolerance of 0.05 ppm for rhubarb.

Tuberous and Corm Vegetables, Subgroup 1C

The submitted field trial data for halosulfuron-methyl on potato, the representative commodity of 

Crop Subgroup 1C, reflect the use of a nonionic surfactant as recommended on the proposed 

label and approximate the proposed PHI. The data are also supported by concurrent storage 

stability data. The number and location of field trials do not fully conform to the OPPTS 

860.1500 guideline; however, all the residue level were below the LOQ when conducted at the 

exaggerated use rates. Therefore, HED is not requesting additional field trials. The available data 

support the proposed use pattern, and HED recommends for a tolerance of 0.05 ppm for Crop 

Subgroup 1C.

Processed Food and Feed

Apple

An additional plot was established at the NJ site using a total seasonal rate of 0.484 lb ai/A 

(~5.1X the proposed maximum seasonal rate), to generate samples for processing; however, 
Page 23 of 47

residues were not detectable in any apple fruit sample. An apple processing study and tolerances 

for apple processed commodities are not required for this action.

Potato

The submitted processing data for potato are acceptable. Residues of halosulfuron-methyl were 

nonquantifiable (<0.05 ppm) in/on potato tubers following treatments at 2X the proposed 

seasonal rate. Residues were also nonquantifiable in processed potato granules/flakes, chips, and 

wet peel. The Agency would have preferred that a trial with an exaggerated rate equal to or 

higher than the maximum theoretical concentration factor of 5X for potato have been conducted. 

However, because of phytotoxicity limitations as reported in the magnitude of the residue trials, 

a new potato processing study will not be required. Based on these data, tolerances for potato 

processed commodities are not needed.

Confined/Field Accumulation in Rotational Crops

Acceptable confined rotational and limited field rotational crop studies were previously 

submitted and reviewed (D188144 & 188814, G.J. Herndon, 3/11/93; D192510,G.F. Kramer,

8/30/93). The results of these studies indicate that metabolites containing the pyrazole moiety

may accumulate in harvested crops planted at intervals greater than one year. The confined 

rotational crop study, conducted at 0.19 lb ai/A, indicated that no measurable residues of 

halosulfuron-methyl were detected in any rotational crop commodities of wheat, soybean, radish 

and lettuce at any plantback interval (30, 120, and 360 days after treatment). The limited field 

rotational crop study, conducted at 0.22 lb ai/A in a split (preplant + postemergence) application, 

with rotated crops of winter wheat, spring wheat, soybean, sugar beet, and leaf lettuce indicated 

that no measurable residues of halosulfuron-methyl were detected in any field rotational crop 

samples, except in one spring wheat forage sample at 0.090 ppm (364-day plantback interval). 

HED previously concluded that the residue of concern in rotational crops is halosulfuron-methyl

(D225273, G.J. Herndon, 10/29/98). 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 also concluded that rotational crop tolerances and restrictions are not required for 

halosulfuron-methyl. 

The proposed uses on okra, pea and bean (succulent shelled and dried), tuberous and corm 

vegetables, and rhubarb are not expected to alter HED’s earlier assessment regarding the 

potential for inadvertent residues in rotatable crops addressed in this registration action. No 

additional data are required. 

Proposed Tolerances

Halosulfuron-methyl tolerances for plant commodities have been established in 40 CFR 

§180.479(a)(2) and are expressed in terms of halosulfuron-methyl, methyl 5-[(4,6-dimethoxy-2-

pyrimidinyl)amino]carbonylaminosulfonyl-3-chloro-1-methyl-1H-pyrazole-4-carboxylate. The 

proposed tolerance expression is consistent with the halosulfuron-methyl tolerances established 

in 40 CFR §180.479(a)(2) and reflect the residues of concern as previously determined by HED.

Halosulfuron-methyl tolerances for livestock commodities are listed in 40 CFR §180.479(a)(1) 

and are expressed in terms of halosulfuron-methyl and its metabolites determined as 3-chloro-1-
Page 24 of 47

methyl-5-sulfamoylpyrazole-4-carboxylic acid (also referred to as 3-CSA, expressed as parent 

equivalents). Residues of halosulfuron-methyl were below the LOQ of 0.05 ppm, when the test 

formulation was applied to the proposed crops according to the conditions and parameters used 

in the field trials. 

Table 4.1.4 presents the proposed/recommended tolerance levels and corrected commodity

definition. HED is currently unable to recommend for a registration and tolerance for Crop 

Subgroup 6C (dried shelled bean (except soybean) and pea) because data are required for dried 

pea including the forages and hay of field pea cultivars. When adequate residue data for dried 

peas become available, the petitioner may again request a tolerance for Subgroup 6C.

Table 4.1.4. Tolerance Summary for Halosulfuron-Methyl.

Commodity (as Defined in Section F) Proposed 

Tolerance 

(ppm)

Recommended 

Tolerance 

(ppm)

Comments; Correct Commodity 

Definition

PEA AND BEAN, SUCCULENT 

SHELLED, SUBGROUP 6B

0.05 0.05 HED recommends a label revision to 

prohibit applications to legumes grown 

for livestock feeds because no residue 

data are available for cowpea forage and 

hay.

Pea and bean, succulent shelled, 

subgroup 6B

VEGETABLE TUBEROUS AND 

CORM, SUBGROUP 1C

0.05 0.05 Vegetable, tuberous and corm, subgroup 

1C

RHUBARB 0.05 0.05 Rhubarb

PEA AND BEAN, DRIED SHELLED, 

EXCEPT SOYBEAN, SUBGROUP 6C

0.05 None Revised Section F. When adequate 

residue data for dried peas become 

available, the petitioner may again 

request a tolerance for Subgroup 6C.

Pea and bean, dried shelled, except 

soybean, subgroup 6C

APPLE 0.05 0.05 The proposed label should be amended 

to remove the instructions pertaining to 

the use of a non-ionic surfactant.

Apple

OKRA 0.05 0.05 The recommended tolerance is based on 

translation of data from fruiting 

vegetables.

Okra

BUSHBERRY SUBGROUP 13-07B 0.05 0.05 The proposed label should be amended 

to remove the instructions pertaining to 

the use of a non-ionic surfactant.

Bushberry subgroup 13-07B

International Residue Limits

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

halosulfuron-methyl in/on crop or livestock commodities Table 4.1.5.
Page 25 of 47

Table 4.1.5. INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name: methyl 

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

pyrimidinyl)amino]carbon

ylaminosulfonyl-3-chloro1-methyl-1H-pyrazole-4-

carboxylate

Common Name:

Halosulfuron-methyl

X Proposed tolerance

□ Reevaluated tolerance

□ Other

Date: 10/2009

Codex Status (Maximum Residue Limits) U. S. Tolerances

X No Codex proposal step 6 or above

□ No Codex proposal step 6 or above for the crops 

requested

Petition Number: PP#9E7577

DP#: 367058

Other Identifier: 

Residue definition (step 8/CXL): N/A Reviewer/Branch: P. Deschamp, N. Dodd/RAB3

Residue definition: halosulfuron-methyl

Crop (s) MRL (mg/kg) Crop(s) Tolerance (ppm)

Pea and bean, succulent 

shelled, Subgroup 6B

0.05

Vegetable, tuberous and corm, 

Subgroup 1C

0.05

Rhubarb 0.05

Pea and bean, dried shelled, 

except soybean, Subgroup 6C

0.05

Apple 0.05

Okra 0.05

Bushberry, Subgroup 13-07B 0.05

Limits for Canada Limits for Mexico

X No Limits

□ No Limits for the crops requested

X No Limits

□ No Limits for the crops requested

Residue definition: N/A Residue definition: N/A

Mexico defers to Codex MRLs or US tolerances for its 

export purposes.

Crop(s) MRL (mg/kg) Crop(s) MRL (mg/kg)

Notes/Special Instructions: S. Funk, 10/15/2009.

Drinking Water Residue Profile 

The drinking water residues used in the dietary risk assessment were provided by EFED in the 

following memorandum: “Halosulfuron-methyl Drinking Water Assessment for Additional Food 

Uses (including Proposed Use on Soybean)” (D358032, M. Barrett, 5/27/2009) and incorporated 

directly into this dietary assessment. Water residues were incorporated in the DEEM-FCID into 

the food categories “water, direct, all sources” and “water, indirect, all sources.” Since the 

application rates associated with the proposed new uses did not exceed the application rate on 

rice (0.125 lb ai/A), a new drinking water assessment was not required for this dietary analysis. 

The Tier I EDWCs for halosulfuron-methyl are based on a maximum annual application rate of 

0.125 lb ai/A for rice. The two screening models, FQPA Index Reservoir Screening Tool (FIRST) 

and Screening Concentration in Ground Water (SCI-GROW), were used for estimating EDWCs of 
Page 26 of 47

halosulfuron-methyl. Estimates for halosulfuron-methyl in surface water based on the FIRST 

model results for rice are 59.2 ppb for acute and chronic concentrations. It should be noted that 

the drinking water estimate based on rice application is an upper bound estimate. The estimate 

for halosulfuron-methyl in groundwater based on the SCI-GROW model result is 0.065 ppb. The 

results are summarized in Table 4.1.6.

Table 4.1.6. Summary of Estimated Surface Water and Groundwater Concentrations for HalosulfuronMethyl.

Surface Water Conc., ppb a Groundwater Conc., ppb b

Acute 59.2 0.065

Chronic (non-cancer) 59.2 0.065

a

From the FIRST model. 

b

From the SCI-GROW model.

4.2 Dietary Exposure and Risk

Halosulfuron-methyl acute and chronic dietary exposure assessments were conducted using the 

Dietary Exposure Evaluation Model software with the Food Commodity Intake Database 

DEEM-FCIDTM, Version 2.03, which incorporates consumption data from USDA’s Continuing 

Surveys of Food Intakes by Individuals (CSFII), 1994-1996 and 1998. 

Acute Dietary Exposure/Risk

For acute dietary analysis, exposure assessment was conducted using tolerance levels and 100 

%CT for all existing and proposed uses. EDWCs from EFED were incorporated directly into the 

exposure analysis. The only population with a toxicological endpoint attributable to a single 

dose of halosulfuron-methyl is identified to be females 13-49 yrs old. The results of the analysis 

indicate that acute risk from the dietary exposure to halosulfuron-methyl did not exceed HED’s 

level of concern for females 13-49 yrs old at less than 1% of the aPAD (Table 4.2.1).

Chronic Dietary Exposure/Risk

For chronic dietary exposure assessment, an estimate of the residue level in each food or foodform (e.g., orange or orange juice) on the food commodity residue list is multiplied by the 

average daily consumption estimate for that food/food form to produce a residue intake estimate. 

The resulting residue intake estimate for each food/food form is summed with the residue intake 

estimates for all other food/food forms on the commodity residue list to arrive at the total 

average estimated exposure. Exposure is expressed in mg/kg body weight/day and as a percent 

of the cPAD. This procedure is performed for each population subgroup. The results are 

summarized in Table 4.2.1. The results show that the chronic dietary (food and drinking water)

exposure to halosulfuron-methyl is below HED’s level of concern for the general U.S. 

population and all population subgroups. The chronic dietary risk estimates are 2% of the cPAD 

for the general U.S. population and 5% of the cPAD for all infants (<1 year old), the most highly

exposed population subgroup.
Page 27 of 47

Table 4.2.1. Summary of Dietary Exposure and Risk 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

0.001705 2

All Infants (< 1 year old) 0.005059 5

Children 1-2 years old 0.003157 3

Children 3-5 years old 0.002823 3

Children 6-12 years old 0.001859 2

Youth 13-19 years old 0.001327 1

Adults 20-49 years old 0.001511 2

Adults 50+ years old 0.001558 2

Females 13-49 years old 0.003401 <1 0.001503 2

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

5.0 RESIDENTIAL (Non-Occupational) EXPOSURE/RISK CHARACTERIZATION

The current petition focuses on the proposed agricultural use of halosulfuron-methyl on 

succulent shelled pea and bean, tuberous and corn vegetables subgroup dried shelled pea and 

bean (except soybean), bushberry, okra, apples, and rhubarb; no residential uses are being 

requested. However, some halosulfuron-methyl labels permit application to commercial and 

residential turf and on other non-crop sites including airports, cemeteries, fallow areas, golf 

courses, landscaped areas, public recreation areas, residential property, road sides, school 

grounds, sod or turf seed farms, sports fields, landscaped areas with established woody

ornamentals and other similar use sites. Such residential handler and postapplication exposures 

were previously assessed (D331643, M. Rust, 9/21/2006). A major portion of that residential 

assessment is reproduced in this document for the purposes of conducting the aggregate exposure 

and risk assessment.

A product containing halosulfuron-methyl, Manage® (EPA Reg No. 524-465), which contains 

75% halosulfuron-methyl, is currently registered for application to commercial and residential 

turf and other non-crop sites including airports, cemeteries, fallow areas, golf courses, 

landscaped areas, public recreation areas, residential property, road sides, school grounds, sod or 

turf seed farms, sports fields, landscaped areas with established woody ornamentals and other 

similar use sites. Manage® may be applied by homeowners or commercial applicators at a rate 

of 0.031 to 0.062 lb ai/acre. No more than 4 applications may be made per use season, for a 

maximum total use rate of 0.125 lb ai/A per season.

Residential handlers may receive short-term dermal and inhalation exposure to halosulfuronmethyl when mixing, loading and applying the formulations. Adults and children may be 

exposed to halosulfuron-methyl residues through dermal contact with turf during postapplication 

activities. In addition, toddlers may receive short- and intermediate-term oral exposure from 

incidental ingestion during postapplication activities. A residential exposure and risk assessment 

was previously conducted for these exposure scenarios (D278588, K. O’Rourke, 8/28/02) and is 

summarized in the following sections
Page 28 of 47

5.1 Residential Handler Exposure

No chemical-specific exposure data for handler activities were submitted to HED in support of 

the registered lawn uses. HED’s Draft Standard Operating Procedures (SOPs) for Residential 

Exposure Assessments, and Recommended Revisions (HED Policy Number 11, revised 22 Feb 

2001), were used as the basis for the residential handler exposure calculations. The handler 

exposure data used in this assessment are from the Outdoor Residential Exposure Task Force 

(ORETF) (MRID 44972201). The ORETF data were used in this assessment in place of PHED 

data for the garden hose-end sprayer scenario. The ORETF data were designed to replace the 

present PHED data with higher-confidence, higher quality data that contain more replicates than 

the PHED data for those scenarios. The upper-bound risk estimate for residential handlers and 

post-application exposure is a MOE of 5,200 (Table 5.1), and it is not of risk concern.

Table 5.1. Adult’s Combined Exposure and Risk Estimates from Residential Lawns.

Adult’s

Scenario

Exposure

Route

Rate

(lb ai/

acre) 

Acres 

Treated

(acres/

day)

PHED 

Unit 

Exposure

(mg/lb ai) 

Short-term

Daily

Dose 

(mg/kg/day)

Shortterm

MOE1

Total

MOE2

1. Mix/load and broadcast 

application of liquid formulation 

(garden hose-end sprayer)

dermal

0.062 0.5

30 0.0043 23,000

inhalation 0.016 0.0000071 7,000,000 5,200

2. Postapplication exposure dermal 0.062 N/A N/A 0.014 7,000

1. Short-term dermal NOAEL = 100 mg/kg/day; Short-term inhalation NOAEL = 50 mg/kg/day.

2. Total MOE = dermal + inhalation exposure from both handler and post-application activities; Total 

MOE=1/(1/dermal MOE+1/inhalation MOE)

5.2 Residential Postapplication Exposure

The following postapplication exposure scenarios resulting from lawn treatment were assessed: 

(1) adult and children 3 to <6 years old post-application dermal exposure, (2) child 3 to <6 years 

old incidental ingestion of pesticide residues on lawns from hand-to-mouth transfer, (3) toddlers’ 

object-to-mouth transfer from mouthing of pesticide-treated turf grass, and (4) children 3 to <6 

years old incidental ingestion of soil from pesticide-treated residential areas. Post-application 

exposures from various activities following lawn treatment are considered to be the most 

common and significant in residential settings. The exposure via incidental ingestion of other 

plant material may occur but is considered negligible. 

The exposure and risk estimates for the residential exposure scenarios are assessed for the day of 

application (day “0") because it is assumed that adults and child 3 to <6 years old could contact 

the lawn immediately after application. Both short- and intermediate-term exposure is expected. 

Dermal postapplication risk was assessed by comparing the dermal exposure values to the 

NOAELs of 100 mg/kg/day and 10 mg/kg/day, respectively. Risk from short-and intermediateterm incidental ingestion by child 3 to <6 years old is assessed by comparing these exposures to 

the NOAELs of 50 mg/kg/day and 10 mg/kg/day, respectively. 

Both short-term and intermediate-term MOEs for each scenario are above the LOC of 100, and 

are not of concern. As mentioned previously, a common effect (i.e., decreased body weight 
Page 29 of 47

gain) was observed in the studies selected for the endpoints for all routes of exposure; therefore, 

MOEs are to be combined where appropriate. The Total MOEs resulting from the combined 

MOEs for adults (summarized in Table 5.1 above) and children (summarized in Table 5.2), are 

also above the LOC of 100, and not of concern.

Table 5.2.. Children’s Combined Exposure and Risk Estimates from Residential Lawns.

Children’s 

Scenarios

TTR/GR/SR0

(ug/cm2or g) 1

Short-Term

PDR0-norm

(mg/kg/day)

Int-Term

PDR0-norm

(mg/kg/day)

ShortTerm

MOE

Int-term

MOE

Total

ShortTerm

MOE

Total

Int-term

MOE

(1) Dermal Contact 0.035 0.024 0.0090 4,200 1,100

3,800 1,000

(2) Hand-to-Mouth 0.035 0.00093 0.00044 54,000 23,000

(3) Mouthing Grass 0.14 0.00023 0.00023 220,000 43,000

(4) Soil Ingestion 0.47 3.1E-6 3.1E-6 16,000,000 3,200,000

1. TTR=turf transferable residue on day “0"; GR=grass residue on day “0"; SR0=soil residue on day “0"; 

Int=intermediate.

5.3 Other (Spray Drift, etc.)

Recreational exposures to turf are expected to be similar to, or in many cases less than, those 

evaluated in Section 5.2, Residential Post-application Exposure; therefore, a separate recreational 

exposure assessment was not included.

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

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

potential source of exposure from ground application methods. As indicated in this assessment, 

halosulfuron-methyl is directly applied to residential turf and does not result in exposures of -

concern to HED. Based on this assessment, HED believes that it is unlikely that there is a higher 

potential for risk of exposure to spray drift from agricultural uses of this chemical.

6.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION

6.1 Acute Aggregate Risk

An acute aggregate risk assessment was conducted for the population subgroup of concern, 

females 13-49 years old. An appropriate endpoint for the general population was not identified; 

therefore, a corresponding assessment is not required. 

For the population of concern, the acute dietary risk assessment reported earlier in Section 4.2

represents acute aggregate risk since drinking water estimates were incorporated directly into 

the analysis. Exposure through food and drinking water sources occupies less than 1% of the 

aPAD for the population of concern, Females 13-49 years old; thus, estimated acute aggregate 

risk does not exceed HED’s level of concern (Table 6.1).
Page 30 of 47

Table 6.1 Acute Aggregate Risk (Food+Water).

Population Subgroup aPAD(mg/kg/day) Exposure (mg/kg/day) % aPAD

Females 13-50 years old 0.5 0.003401 <1 

6.2 Short-Term Aggregate Risk

The short-term aggregate risk assessment estimates risks likely to result from exposure to 

halosulfuron-methyl residues from food, drinking water, and residential pesticide uses. High-end 

estimates of residential exposure are used, while average values are used for food and drinking 

water exposure (i.e., chronic exposures). Since the LOC is the same for all routes of exposure, 

exposures are compared to the short-term NOAEL corresponding to the route of exposure to 

calculate a route-specific MOE. Then an aggregate MOE was calculated by combining MOEs 

across all relevant routes of exposure (oral, dermal and inhalation). 

A short-term risk assessment is required for adults because there is a residential handler exposure 

scenario. In addition, a short-term risk assessment is required for infants and children because 

there is a residential post-application exposure scenario for infants and children. 

Results of the short-term aggregate risk assessment are summarized in Table 6.2 below. Shortterm aggregate MOEs ranged from 2,800 to 4,800. The MOE for the U.S. population is 4,700. 

The most highly exposed subgroup was all infants (< 1 year old), with a MOE of 2,800. These 

estimates of short-term aggregate risk do not exceed HED’s level of concern.

Table 6.2. Short-Term Aggregate Risk Calculations. 

Population LOC for 

Aggregate

Risk1

MOE

food & water2

MOE

oral3

MOE

dermal4

MOE 

inhalation5

Aggregate MOE

(food and 

residential)6

U.S. 

Population 100

29,000 N/A 5,500 7,000,000 4,700

Females, 13-49 

years old

33,000 N/A 5,500 7,000,000 4,800

All Infants 

(<1 year old)

9,900 43,000 4,200 N/A 2,800

Adults 50+ 

years

32,000 N/A 5,500 7,000,000 4,700

1 HED’s LOC is a MOE of at least 100 (10X for inter-species variability and 10X for intra-species variability)

2 MOE food = [(short-term oral NOAEL=50 mg/kg/day) / (chronic dietary exposure)] Dietary exposure from Table 4.4.2.

3 MOE oral = [(short-term oral NOAEL=50 mg/kg/day) / (oral residential exposure)] Residential exposure from Table 5.2.

4 MOE dermal = [(short-term dermal NOAEL=100 mg/kg/day) / (high-end dermal residential exposure (for adult, included

mix/load plus post-application exposure))]. Residential exposure from Tables 5.1 and 5.2.

5 MOE inhalation = [(short-term inhalation NOAEL=50 mg/kg/day) / (high-end inhalation residential exposure)] 

Residential MOEs from Table 5.1.

6 Aggregate MOE (food and residential) = 1 [(1/MOE food) + (1/MOE oral) + (1/MOE dermal) + (1/MOE inhalation)].

6.3 Intermediate-Term Aggregate Risk
Page 31 of 47

The intermediate-term aggregate risk assessment estimates risks likely to result from exposure to 

halosulfuron-methyl residues from food, drinking water, and residential pesticide uses. High-end 

estimates of residential exposure are used, while average values are used for food and drinking 

water exposure (i.e., chronic exposures). Intermediate-term exposures across all routes of 

exposure were summed and compared to the intermediate-term NOAEL (10 mg/kg/day) from the 

13-week subchronic toxicity study in dogs, since this study and endpoint are to be used for all 

intermediate-term risk assessments (LOAEL = 40 mg/kg/day based on decreased body weight 

gains and food efficiency along with hematological and clinical chemistry changes).

The aggregate MOEs for adults include intermediate-term dermal and inhalation exposures for 

residential handlers and post-application dermal exposures from activities on turfgrass previously

treated with halosulfuron-methyl. The inclusion of intermediate-term residential handler 

exposures in the aggregate MOE is conservative (protective), since intermediate-term

exposure of handlers is unlikely.

Results of the intermediate-term aggregate risk assessment are summarized in Table 6.3 below. 

Intermediate-term aggregate MOEs ranged from 500 to 680. The MOE for the U.S. population 

is 500. The most highly exposed children’s subgroup was all infants (< 1 year old), with a MOE

of 680. These estimates of aggregate risk do not exceed HED’s level of concern.

Table 6.3. Intermediate-Term (IT) Aggregate Risk Calculations

Population

LOC for 

Aggregate 

Risk1

Exposure 

Food & 

Water 

(mg/kg/day)

Exposure oral

(mg/kg/day)2

Dermal 

Exposure 

(mg/kg/day) 3

Exposure 

inhalation 

(mg/kg/day)4

Aggregate 

MOE (food and 

residential)5

U.S. Population 

(total)

100

0.001705 N/A 0.0183 0.0000071 500

Females, 13-49

years old 0.001503 N/A 0.0183 0.0000071 500

All Infants 

(<1 year old) 0.005059 0.0006731 0.0090

N/A 680

Adults 50+ years 

old 0.001558 N/A 0.0183 0.0000071 500

1. LOC=100 (10x for inter-species variability*10x for intra-species variability).

2. Incidental oral exposure applies only to subpopulations consisting of infants and children. From Table 5.2.

3 Dermal exposure from Table 5.1 (0.0043 + 0.014 mg/kg/day = 0.0183 mg/kg/day).

4. Inhalation exposure from Table 5.1.

5 Aggregate MOE (food, water and residential) = IT NOAEL (10 mg/kg/day)/(food & water exposure + dermal 

exposure + inhalation exposure + incidental oral exposure).

7.0 CUMULATIVE RISK CHARACTERIZATION/ASSESSMENT

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding for 

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 
Page 32 of 47

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

chemicals, see the policy statements released by EPA’s OPP concerning common mechanism 

determinations and procedures for cumulating effects from substances found to have a common 

mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

8.0 OCCUPATIONAL EXPOSURE/RISK PATHWAY

Workers may be exposed to halosulfuron-methyl during mixing, loading, applying, and 

postapplication activities. Based on the proposed application rates, short- and intermediate-term 

exposure may occur. Chronic exposure (6 months of continuous exposure) is not expected.

8.1 Short- and Intermediate-Term Handler Exposure and Risk

Halosulfuron-methyl may be applied using handgun and groundboom equipment. The 

application methods, maximum application rates, and use sites are summarized in Tables 2.1 and

2.2. Chemical-specific data for assessing exposure during pesticide handling activities were not 

submitted to the Agency in support of this Section 3 application. It is HED policy to use data 

from PHED Version 1.1 to assess handler exposures for regulatory actions when chemicalspecific data are not available (HED ExpoSAC, SOP No.7, January 1999) or from the Outdoor 

Residential Exposure Task Force (ORETF). 

Standard values established by the ExpoSAC were used for acres treated per day and body 

weight. For short-term dermal occupational exposure, the toxicity endpoint was decreased body 

weight gain, and the point of departure was 100 mg/kg/day (NOAEL) based on the results of a 

21-day dermal toxicity study in rats. For intermediate-term dermal exposure assessment, the 

toxicity endpoint was also decreased body weight gains and reduced food efficiency along with 

hematological changes; the point of departure was 10 mg/kg/day (NOAEL) based on a 13-week 

oral toxicity in dogs. Because this point of departure is derived from an oral study, intermediateterm dermal doses were adjusted to account for 75% dermal absorption.

For short-term inhalation occupational exposure, the point of departure (50 mg/kg/day) was 

derived from an oral developmental rabbit study in which decreased body weight gains were 

observed at the LOAEL of 150 mg/kg/day. For the intermediate-term inhalation occupational 

exposure, the point of departure (10 mg/kg/day) was based on an oral 13-week oral toxicity study

in dogs in which decreased body weight gains and food efficiency along with hematology and 

clinical chemistry changes were observed at the LOAEL of 40 mg/kg/day. Since no inhalation 

absorption data are available, toxicity by the inhalation route is considered to be equivalent to the 

estimated toxicity by the oral route of exposure.

Resulting dermal and inhalation risk estimates were combined into total risk estimates because of 

a common effect (i.e., body weight gain decreases) seen in the studies selected for the endpoints 

for both routes of exposure. The LOC for occupational exposure is for MOEs less than 100.

Halosulfuron-methyl is characterized as “not likely to be carcinogenic to humans” based on lack 

of evidence from oral studies in rats and mice. Therefore, cancer risk was not assessed.
Page 33 of 47

Summaries of the exposure and risk estimates for occupational handlers are presented in Table 

8.1.1 (Short-Term) and Table 8.1.2 (Intermediate-Term). All combined MOEs exceed the LOC 

of 100, and therefore, are not of concern.
Page 34 of 47

Table 8.1.1 . Short-Term Agricultural Handler Exposure and Risk for Halosulfuron-Methyl.

Exposure Scenario Crop or Target

App 

Ratea

(lb 

ai/A)

Acres 

Treated 

Dailyb

Unit Exposurec Dose

(mg/kg/day) MOEs

Baseline 

Dermal

mg/lb ai

PPE-G

Dermal

mg/lb ai

Baseline 

Inhalation 

μg/lb ai

Baseline 

Dermald,h

PPE-G 

Dermali

Baseline 

Inhalatione,h

Baseline 

Dermalf

PPE-G

Dermal

Baseline 

Inhalationg

Combined 

Baseline 

Dermal + 

Inhalationj

Combined 

PPE-G + 

Baseline 

Inhalationk

Mixer/Loader

Mixing/Loading Dry 

Flowables for 

Groundboom 

Applications (PHED)

Succulent shelled 

peas and bean 0.023 80 0.066 0.066 0.77 0.0017 0.0017 0.00002 58,000 58,000 2,500,000 56,000 56,000

Tuberous and corm 

vegetables; 

Rhubarb; 

Bushberry; 

Dried shelled pea and 

bean (except 

soybean) (West of the 

Rockies); 

Okra; 

Apples (East of the 

Rockies)

0.047 80 0.066 0.066 0.77 0.0035 0.0035 0.000041 28,000 28,000 1,200,000 28,000 28,000

Dried shelled pea and 

bean (except 

soybean) (East of the 

Rockies)

0.031 80 0.066 0.066 0.77 0.0023 0.0023 0.000027 43,000 43,000 1,800,000 42,000 42,000

Apples (West of the 

Rockies) 0.094 80 0.066 0.066 0.77 0.0071 0.0071 0.000083 14,000 14,000 600,000 14,000 14,000

Applicator

Applying Sprays via

Groundboom Equipment 

(PHED)

Succulent shelled 

peas and bean 0.023 80 0.014 0.014 0.74 0.00037 0.00037 0.000019 270,000 270,000 2,600,000 250,000 250,000

Tuberous and corm 

vegetables;

Rhubarb;

Bushberry;

Dried shelled pea and 

bean (except 

soybean) (West of the 

Rockies);

Okra; Apples

(East of the Rockies)

0.047 80 0.014 0.014 0.74 0.00075 0.00075 0.00004 130,000 130,000 1,300,000 120,000 120,000
Page 35 of 47

Table 8.1.1 . Short-Term Agricultural Handler Exposure and Risk for Halosulfuron-Methyl.

Exposure Scenario Crop or Target

App 

Ratea

(lb 

ai/A)

Acres 

Treated 

Dailyb

Unit Exposurec Dose

(mg/kg/day) MOEs

Baseline 

Dermal

mg/lb ai

PPE-G

Dermal

mg/lb ai

Baseline 

Inhalation 

μg/lb ai

Baseline 

Dermald,h

PPE-G 

Dermali

Baseline 

Inhalatione,h

Baseline 

Dermalf

PPE-G

Dermal

Baseline 

Inhalationg

Combined 

Baseline 

Dermal + 

Inhalationj

Combined 

PPE-G + 

Baseline 

Inhalationk

Dried shelled pea and 

bean (except 

soybean) (East of the 

Rockies)

0.031 80 0.014 0.014 0.74 0.0005 0.0005 0.000026 200,000 200,000 1,900,000 180,000 180,000

Apples (West of the 

Rockies) 0.094 80 0.014 0.014 0.74 0.0015 0.0015 0.000079 66,000 66,000 630,000 60,000 60,000

Mixer/Loader/Applicator

Mixing/Loading/Applying 

Dry Flowables 

Concentrates with a 

Handgun Sprayer (LCO 

ORETF data)

Rhubarb; Bushberry; 

Dried shelled pea and 

bean (except 

soybean) (West of the 

Rockies); 

Apples (East of the 

Rockies); Okra

0.047 25 No Data 0.58 22 No Data 0.0097 0.00037 No Data 10,000 140,000 No Data 9,300

Dried shelled pea and 

bean (except 

soybean) (East of the 

Rockies)

0.031 25 No Data 0.58 22 No Data 0.0064 0.00024 No Data 16,000 210,000 No Data 14,000

Apples (West of the 

Rockies) 0.094 25 No Data 0.58 22 No Data 0.019 0.00074 No Data 5,100 68,000 No Data 4,800

a Application Rates based on proposed uses on label for halosulfuron-methyl product Sandea® Herbicide (EPA Reg. No. 81880-18).

b Exposure Science Advisory Council Policy No. 9.1

c Unit Exposures based on PHED Version 1.1. 

d Dermal Dose (mg/kg/day) = daily unit exposure (mg/lb ai) x application rate (lb ai/acre) x acres treated / body weight (70 kg).

e Inhalation Dose (mg/kg/day) = daily unit exposure (μg/lb ai) x application rate (lb ai/acre) x acres treated / body weight (70 kg). 

f Dermal MOE = NOAEL (100 mg/kg/day) / dermal daily dose (mg/kg/day). Level of concern = 100.

g Inhalation MOE = NOAEL (50 mg/kg/day) / inhalation daily dose (mg/kg/day). Level of concern = 100.

h Baseline Dermal: Long-sleeve shirt, long pants, and no gloves; Baseline Inhalation: no respirator.

i Baseline plus Gloves Dermal: Baseline plus chemical-resistant gloves.

j Combined Baseline Dermal + Inhalation MOE = 1 / (1/Baseline Dermal MOE + 1/Baseline Inhalation MOE).

k Combined PPE-G + Baseline Inhalation MOE = 1 / (1/PPE-G Dermal MOE + 1/Baseline Inhalation MOE). 
Page 36 of 47

Table 8.1.2. Intermediate-Term Agricultural Handler Exposure and Risk for Halosulfuron-Methyl.

Exposure Scenario Crop or Target

App 

Ratea

(lb 

ai/A)

Acres 

Treated 

Dailyb

Unit Exposurec Dose

(mg/kg/day) MOEs

Baseline 

Dermal

mg/lb ai

PPE-G

Dermal

mg/lb ai

Baseline 

Inhalation 

μg/lb ai

Baseline 

Dermald,h

PPE-G 

Dermali

Baseline

Inhalatione,h

Baseline 

Dermalf

PPE-G

Dermal

Baseline 

Inhalationg

Combined 

Baseline 

Dermal + 

Inhalationj

Combined 

PPE-G + 

Baseline 

Inhalationk

Mixer/Loader

Mixing/Loading Dry 

Flowables for 

Groundboom Applications 

(PHED)

Succulent shelled peas 

and bean 0.023 80 0.066 0.066 0.77 0.0013 0.0013 0.00002 7,700 7,700 490,000 7,600 7,600

Tuberous and corm 

vegetables; Rhubarb; 

Bushberry; Dried 

shelled pea and bean 

(except soybean) (West 

of the Rockies); Okra; 

Apples (East of the 

Rockies)

0.047 80 0.066 0.066 0.77 0.0027 0.0027 0.000041 3,800 3,800 240,000 3,700 3,700

Dried shelled pea and 

bean (except soybean) 

(East of the Rockies) 0.031 80 0.066 0.066 0.77 0.0018 0.0018 0.000027 5,700 5,700 370,000 5,600 5,600

Apples (West of the 

Rockies) 0.094 80 0.066 0.066 0.77 0.0053 0.0053 0.000083 1,900 1,900 120,000 1,900 1,900

Applicator

Applying Sprays via

Groundboom Equipment 

(PHED)

Succulent shelled peas 

and bean 0.023 80 0.014 0.014 0.74 0.00028 0.00028 0.000019 36,000 36,000 510,000 34,000 34,000

Tuberous and corm 

vegetables;Rhubarb;

Bushberry;Dried shelled 

pea and bean (except 

soybean) (West of the 

Rockies);

Okra;Apples

(East of the Rockies)

0.047 80 0.014 0.014 0.74 0.00056 0.00056 0.00004 18,000 18,000 250,000 17,000 17,000

Dried shelled pea and 

bean (except soybean) 

(East of the Rockies) 0.031 80 0.014 0.014 0.74 0.00037 0.00037 0.000026 27,000 27,000 380,000 25,000 25,000

Apples (West of the 

Rockies) 0.094 80 0.014 0.014 0.74 0.0011 0.0011 0.000079 8,900 8,900 130,000 8,300 8,300
Page 37 of 47

Table 8.1.2. Intermediate-Term Agricultural Handler Exposure and Risk for Halosulfuron-Methyl.

Exposure Scenario Crop or Target

App 

Ratea

(lb 

ai/A)

Acres 

Treated 

Dailyb

Unit Exposurec Dose

(mg/kg/day) MOEs

Baseline 

Dermal

mg/lb ai

PPE-G

Dermal

mg/lb ai

Baseline 

Inhalation 

μg/lb ai

Baseline 

Dermald,h

PPE-G 

Dermali

Baseline

Inhalatione,h

Baseline 

Dermalf

PPE-G

Dermal

Baseline 

Inhalationg

Combined 

Baseline 

Dermal + 

Inhalationj

Combined 

PPE-G + 

Baseline 

Inhalationk

Mixer/Loader/Applicator

Mixing/Loading/Applying 

Dry Flowables 

Concentrates with a 

Handgun Sprayer (LCO 

ORETF data)

Rhubarb; Bushberry; 

Dried shelled pea and 

bean (except soybean) 

(West of the Rockies); 

Apples (East of the 

Rockies); Okra

0.047 25 No Data 0.58 22 No Data 0.0073 0.00037 No Data 1,400 27,000 No Data 1,300

Dried shelled pea and 

bean (except soybean) 

(East of the Rockies)

0.031 25 No Data 0.58 22 No Data 0.0048 0.00024 No Data 2,100 41,000 No Data 2,000

Apples (West of the 

Rockies) 0.094 25 No Data 0.58 22 No Data 0.015 0.00074 No Data 680 14,000 No Data 650

a Application Rates based on proposed uses on label for halosulfuron-methyl product Sandea® Herbicide (EPA Reg. No. 81880-18).

b Exposure Science Advisory Council Policy No. 9.1. 

c Unit Exposures based on PHED Version 1.1. 

d Dermal Dose (mg/kg/day) = daily unit exposure (mg/lb ai) x application rate (lb ai/acre) x acres treated x dermal absorption factor (75%) / body weight (70 kg).

e Inhalation Dose (mg/kg/day) = daily unit exposure (μg/lb ai) x application rate (lb ai/acre) x acres treated / body weight (70 kg). 

f Dermal MOE = NOAEL (10 mg/kg/day) / dermal daily dose (mg/kg/day). Level of concern = 100.

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

h Baseline Dermal: Long-sleeve shirt, long pants, and no gloves; Baseline Inhalation: no respirator.

i Baseline plus Gloves Dermal: Baseline plus chemical-resistant gloves. 

j Combined Baseline Dermal + Inhalation MOE = 1 / (1/Baseline Dermal MOE + 1/Baseline Inhalation MOE).

k Combined PPE-G + Baseline Inhalation MOE = 1 / (1/PPE-G Dermal MOE + 1/Baseline Inhalation MOE). 
Page 38 of 47

8.2 Postapplication Exposure/Risk

8.2.1 Data and Assumptions for Postapplication Exposure Scenarios

Inhalation: Based on the Agency's current practices, a quantitative postapplication inhalation 

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

is not applied using airblast aerial equipment or another method that could result in higher 

postapplication inhalation exposure than other application methods. Further halosulfuron-methyl 

has low vapor pressure. 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). The Agency is in the process of evaluating the SAP 

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

subsequently, the way to incorporate postapplication inhalation exposure into the Agency's risk 

assessments. If new policies or procedures are put into place, the Agency may revisit the need 

for a quantitative postapplication inhalation exposure assessment for halosulfuron-methyl.

Dermal: Most of the proposed uses for halosulfuron-methyl are ground-directed uses where no 

crop foliage is treated. Currently, HED has no transfer coefficients (TCs) or other data to assess 

postapplication dermal exposures to soil by occupational workers. In general, such exposures 

are considered to be negligible. Therefore, for the proposed soil-directed uses, postapplication 

exposures and risks to occupational workers were not quantitatively assessed. However, some of 

the proposed uses for halosulfuron-methyl are for postemergent applications when crop foliage is 

present. Postapplication exposure and risk were assessed for these proposed uses. This 

assessment is considered to be a Tier I, screening level estimate, demonstrating that there are 

minimal potential risks to workers re-entering fields treated with postemergent applications of 

halosulfuron-methyl.

Since no postapplication data was submitted in support of this registration action, dermal 

exposures during postapplication activities were estimated using dermal TCs from the ExpoSAC

SOP No. 003.1: Agricultural Transfer Coefficients, August 2000, and the following assumptions:

 Application Rate = 0.047 lb ai/A for tuberous and corm vegetables, bushberries, 

and dried shelled peas and beans (West of the Rockies); and

0.031 lb ai/A for dried shelled peas and beans (East of the 

Rockies). 

 Exposure Duration = 8 hours per day

 Body Weight = 70 kg for average adult

 Dermal Absorption = 100% for short-term and 75% for intermediate-term

 Fraction of ai retained on foliage is assumed to be 20% (0.2) on day zero for agricultural 

crops. This fraction is assumed to further dissipate at the rate of 10% (0.1) per day on 

following days. These are default values established by HED ExpoSAC.

Foliar residue is expected to be very low during postapplication activities. Since halosulfuron-
Page 39 of 47

methyl is typically applied early in the season prior to flowering, the postapplication tasks are 

unlikely to encounter foliar residues of concern. The dermal exposure risk estimates for 

postapplication activities are summarized below in Table 8.2.1.1.

Table 8.2.1.1. Anticipated Postapplication Activities and Dermal Transfer Coefficients.

Proposed Crop Policy Crop Group 

Category

Exposure 

Potential

Transfer 

Coefficients 

(cm2/hr)

Activities

Tuberous and Corm 

Vegetables Vegetable, “Root”

Medium 1,500 Irrigation, Scouting

Low 300 Hand Weeding

Bushberries Vine/Trellis Low 500 Hedging, Irrigation, Hand 

Weeding, Scouting

Dried Shelled Peas 

and Beans

Field/Row Crop, 

Low/Medium Low 100 Irrigation, Scouting, Hand Weeding

8.2.2 Agricultural Post-application Exposure and Risk

The postapplication exposure associated with agricultural crops is summarized in Table 8.2.1.2. 

All scenarios resulted in MOEs greater than 100 on day 0 (12 hours after application) and,

therefore, do not exceed HED’s LOC.

Table 8.2.1.2. Postapplication Exposure and Risk for Halosulfuron-Methyl.

Crop Activity

Transfer

Coefficienta

(cm2/hr)

DATb DFRc

(μg/cm2)

Short-Term Intermediate-Term

Daily Dermal 

Dosed

(mg/kg/day)

MOEe

Daily 

Dermal 

Dosed

(mg/kg/day)

MOEe

Tuberous and 

corm 

vegetables

Irrigation, scouting 1,500 0

(12 hours) 0.1054 0.018 5,500 0.014 740

Hand weeding 300 0

(12 hours) 0.1054 0.0036 28,000 0.0027 3,700

Bushberry

Hedging, irrigation, 

hand weeding, 

scouting

500 0

(12 hours) 0.1054 0.0060 17,000 0.0045 2,200

Dried shelled 

peas and 

beans

(West of 

Rockies)

Irrigation, 

Scouting,

Hand weeding

100 0

(12 hours) 0.1054 0.0012 83,000 0.00090 11,000

Dried shelled 

peas and 

beans

(East of 

Rockies)

Irrigation, 

Scouting,

Hand weeding

100 0

(12 hours) 0.0695 0.00079 130,000 0.00060 17,000

a Transfer coefficients and associated activities from ExpoSAC SOP No. 003.1 “Agricultural Transfer Coefficients,” 8/17/2000. 

b DAT = Days after treatment needed to reach the LOC of 100; DAT 0 = the day of treatment, after sprays have dried; assumed 

to be approximately 12 hours. 

c DFR (μg/cm2) = Application rate (lb ai/A) x (1- daily dissipation rate) t x CF (4.54E+8 μg/lb) x CF (2.47E-8 A/cm2) x 20% 

DFR after initial treatment.

d Daily Dose = [(DFR x TC x Dermal absorption x 8-hr Exposure Time)] / [(CF: 1000 μg/mg) x (70 kg Body Weight)] (Shortterm dermal absorption factor = 100%; Intermediate-term dermal absorption factor = 75%). 

e MOE = NOAEL/Daily Dose (Short-Term Dermal NOAEL = 100 mg/kg/day; Intermediate-Term Dermal NOAEL = 10 

mg/kg/day).
Page 40 of 47

Restricted-Entry interval 

The halosulfuron-methyl technical material has been classified in Toxicity Category III for acute 

dermal toxicity and Toxicity Category IV for primary eye irritation and primary skin irritation. 

Per the Worker Protection Standard (WPS), a 12-hr restricted entry interval (REI) is required for 

chemicals classified under Toxicity Category III or IV. The current GWN-3061 label has a 12-

hour REI, which complies with the WPS. 

9.0 DATA NEEDS/LABEL RECOMMENDATIONS

9.1 Toxicology

870.3465 28-Day Inhalation – Rat

A 28-day inhalation toxicity study in the rat is required due to concern for repeated 

exposure via the inhalation route based on the use pattern.

870.7800 Immunotoxicity

Under the new rule for data requirements as presented in 40 CFR Part 158, an 

immunotoxicity study is required.

9.2 Residue Chemistry

860.1200 Directions for Use

● For Crop Subgroup 6B (pea and bean, succulent shelled), the label(s) should be amended 

to prohibit applications to legumes grown for livestock feeds because no residue data are 

available for cowpea forage and hay.

● For Crop Subgroup 13-07B (bushberry), the label(s) should be amended to remove the 

instructions pertaining to the use of a non-ionic surfactant. If it is IR-4’s intention to add 

a nonionic surfactant when Sandea® Herbicide is applied to these crops, then additional 

field trial data are required.

 For Crop Subgroup 6C (dried pea and bean (except soybean)), the labels should be 

amended to remove the use directions for Crop Subgroup 6C. 

860.1500 Crop Field Trials

Prior to granting a registration on Crop Subgroup 6C (dried shelled pea and bean (except 

soybean)), data on dried pea including the forages and hay of field pea cultivars are 

required from a minimum of five field trials. The requested field trials should reflect 

total application rates of 0.047 lb ai/A per crop cycle or 0.094 lb ai/A per year, a 

minimum 30-day PHI, and the incorporation of a non-ionic surfactant in the spray

mixture. A revised Section F should be submitted removing the request for Crop 

Subgroup 6C (dried shelled pea and bean (except soybean)).
Page 41 of 47

860.1650 Submittal of Analytical Reference Standards

Analytical reference standards for the 3-CSA (3-chlorosulfonamide acid) metabolite and 

the RRE of halosulfuron-methyl must be submitted to the EPA National Pesticide 

Standards Repository.

REFERENCES

2002 Hazard Assessment

HALOSULFURON-METHYL: - Report of the Hazard Identification Assessment Review 

Committee. 08/23/2002.

2006 Risk Assessment

Halosulfuron-methyl: Human Health Risk Assessment for Propose Uses on Alfalfa. D331643, M. 

Clock-Rust, 09/21/2006.

2009 Risk Assessment

Halosulfuron-methyl: Human Health Risk Assessment for Propose Uses on Soybean. D35803, W. 

Phang, 06/30/2009

Residue Chemistry Assessment

Halosulfuron-methyl. Application for Section 3 Registration of Sandea® Herbicide (EPA Reg. 

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

and Bean, Succulent Shelled, Subgroup 6B; Vegetable, Tuberous and Corm, Subgroup 1C; 

Rhubarb; Bushberry Subgroup 13-07B; Pea and Bean, Dried Shelled, Except Soybean, 

Subgroup 6C; Apple; and Okra. Summary of Analytical Chemistry and Residue Data. D367058, 

Debra Rate, 03/03/2010

Dietary Exposure Analysis

Halosulfuron-methyl Acute and Chronic Aggregate Dietary (Food and Drinking Water) 

Exposure and Risk Assessments for the Section 3 Registration Action on Pea and Bean, 

Succulent Shelled, Subgroup 6B; Vegetable, Tuberous and Corm, Subgroup 1C; Rhubarb; 

Bushberry Subgroup 13-07B; Apple; and Okra. D367059, Debra Rate, 03/04/2010

Occupational and Residential Exposure Assessment

Halosulfuron-Methyl. Occupational and Residential Exposure Assessment for Proposed Field 

Use of Halosulfuron-Methyl on Succulent Shelled Peas and Beans (Subgroup 6B), Tuberous and 

Corm Vegetables (Subgroup 1C), Rhubarb, Bushberry (Subgroup 13-07B), Dried Shelled Peas 

and Beans (Except Soybean, Subgroup 6C), Apples, and Okra. D367060
Page 42 of 47

Drinking Water Assessment

Halosulfuron-Methyl Drinking Water Assessment for Additional Food Uses (Including Proposed 

Use on Soybeans). D358031, M. Barrett, 05/27/2009.
Page 43 of 47

Attachment A: Toxicology Profile 

Table 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 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/ 

Carcinogenicity in 

rats

42661418 (1992)/ 

Acceptable/Guideline

Doses: 0, 10, 100, 1000, or 

2500, 5000 (males only) ppm 

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

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

marginal decrease in body weight gain in both males 

and females.
Page 44 of 47

Table 2. Toxicity Profile of Halosulfuron-Methyl Technical (Repeated dosing and others).

Guideline 

No.

Study Type MRID No. 

(Date)/Classification/ Doses

Results

(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)

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 

rats.

45754701 (1994) and 

46199501 (1989)[positive 

control study]/ 

Acceptable/Guideline

Doses: 0, 200, 600, or 2000 

mg/kg (limit dose)

NOAEL = 600 mg/kg. 

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

in males. 
Page 45 of 47

Table 2. Toxicity Profile of Halosulfuron-Methyl Technical (Repeated dosing and others).

Guideline 

No.

Study Type MRID No. 

(Date)/Classification/ Doses

Results

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.

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. 
Page 46 of 47

Attachment B: Rationale for Requiring the Studies

Guideline Number: 870.3465

Study Title: 90-Day Inhalation Toxicity 

Rationale for Requiring the Data

The 28-day inhalation toxicity study evaluates the potential hazard of a pesticide chemical following 

repeated inhalation exposures. This study is critical for pesticides with use pattern in which there is 

potential for repeated human exposures (e.g., professional applicators, green house use etc) exposure. 

The study design simulates the route of human exposure (inhalation). In this study animals are 

exposed (nose/whole body) to aerosol concentrations of the test material for 6 hours/day, 5 day/week 

for 28 days. A detailed toxicological examination including the histopathology of the respiratory

system is conducted. This is route-specific study would provide data for hazard characterization, 

dose response assessment, and a dose and endpoint for assessing potential risks via the inhalation 

route. 

Practical Utility of the Data

How did the Agency make its re-registration decision without these data? 

A subchronic inhalation study provides critical scientific information needed to characterize potential 

hazard to human population on the respiratory system from pesticide exposure. In the case of

halosufluron-methyl, subchronic inhalation study is not available; an oral toxicity study is employed 

for toxicity endpoint and points of departure selections. Absorption via the inhalation route is 

presumed to be equivalent to oral absorption, and the effects seen in the oral toxicity study are also 

presumed to be similar to those resulted from the inhalation study. A 28-day repeated exposure study

that follows the Test Guidelines (870.3465) will characterize hazard and provide data for a much 

accurate inhalation risk assessment.

How will the data be used? 

This study will identify hazard (i.e., provide a dose and endpoint) following longer repeated 

exposures, this data will be used in risk assessments, and will result in the removal of the database 

uncertainty factor.
Page 47 of 47

Guideline Number: 870.7800

Study Title: Immunotoxicity

Rationale for Requiring the Data

This is a new data requirement under 40 CFR Part 158 as a part of the data requirements 

for registration of a pesticide (food and non-food uses). 

The Immunotoxicity Test Guideline (OPPTS 870.7800) prescribes functional 

immunotoxicity testing and is designed to evaluate the potential of a repeated chemical 

exposure to produce adverse effects (i.e., suppression) on the immune system. 

Immunosuppression is a deficit in the ability of the immune system to respond to a 

challenge of bacterial or viral infections such as tuberculosis (TB), Severe Acquired 

Respiratory Syndrome (SARS), or neoplasia. Because the immune system is highly

complex, studies assessing functional immunotoxic endpoints are helpful in fully

characterizing a pesticide’s potential immunotoxicity. These data will be used in 

combination with data from hematology, lymphoid organ weights, and histopathology in 

routine chronic or subchronic toxicity studies to characterize potential immunotoxic

effects. 

Practical Utility of the Data

How will the data be used?

These animal studies can be used to select endpoints and doses for use in risk assessment 

of all exposure scenarios and are considered a primary data source for reliable reference 

dose calculation. For example, animal studies have demonstrated that immunotoxicity in 

rodents is one of the more sensitive manifestations of TCDD (2,3,7,8-tetrachlorodibenzop-dioxin) among developmental, reproductive, and endocrinologic toxicities. 

Additionally, the EPA has established an oral reference dose (RfD) for tributyltin oxide 

(TBTO) based on observed immunotoxicity in animal studies (IRIS, 1997).

How could the data impact the Agency's future decision-making?

If the immunotoxicity study shows that the test material poses either a greater or a 

diminished risk than that given in the interim decision’s conclusion, the risk assessments 

for the test material may need to be revised to reflect the magnitude of potential risk 

derived from the new data.

If the Agency does not have this data, a 10X database uncertainty factor may be applied 

for conducting a risk assessment from the available studies.