Rimsulfuron Human Health Risk Assessment DP. No. 408722 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: July 2, 2014 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: Rimsulfuron. Human Health Risk Assessment for Proposed Section 3 Use on 

Acetolactase Synthase (ALS) Tolerant Grain Sorghum. 

PC Code: 129009 

Decision No.: 473406 

Petition No.: 2F8131 

Assessment Type: Single Chemical/ Aggregate 

TXRNo.: NA 

MRIDNo.: NA 

DP Barcode: D408722 

Registration Nos.: 352-748,352-816 

Regulatory Action: Section 3 

Case No.: NA 

CAS No.: 122931-48-0 

40 CFR: §180.478 

FROM: Cassi Walls, Ph.D., Risk Assessor " 

~ 

.: 2- vJJ~ / 

Myron Ottley, Ph.D., Senior Toxicologist 1t()J{)t~ Meheret Negussie, Chemist HeAerd- ~t... 

Risk Assessment Branch III (RAB 3) 

Health Effects Division (HED; 7509P) 

THROUGH: Christine Olinger, Branch Chief V#J~ Risk Assessment Branch III (RAB 3g I/) r 

RAB3/HED (7509P) 

TO: Kable Davis, RM 25 

Herbicide Branch (HB) 

Registration Division (RD; 7505P) 

The Registration Division (RD) of Office of Pesticide Programs (OPP) has requested that the 

Health Effects Division (HED) evaluate hazard and exposure data and conduct dietary, 

occupational, and aggregate exposure assessments, to estimate the risk to human health that will 

result from the proposed use ofrimsulfuron on Acetolactase Synthase (ALS) herbicide tolerant 

sorghum. The HED team members contributing to this risk assessment include Cassi Walls (risk 

assessment and occupational/residential assessments)), Myron Ottley (hazard reevaluation), and 

Meheret Negussie (residue chemistry and dietary risk assessment). -

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Rimsulfuron Human Health Risk Assessment DP. No. 408722 

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

2.0 HED Recommendations ................................................................................................... 6 

2.2.1 Enforcement Analytical Method ......................................................................... 6 

2.2.2 Recommended Tolerances ............ .......................................... .............................. 6 

2.2.3 Revisions to Petitioned-For Tolerances ........ ...................................................... 7 

2.2.4 International Harmonization .. ............... .............................................................. 7 

2.3 Label Recommendations ...................................................................................... 7 

2.3.1 Recommendations from Residue Reviews .......................................................... 7 

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

3.1 Chemical Identity .................................................................................................. 8 

3.2 Physical and Chemical Properties ............................................. .......................... 8 

3.3 Pesticide Use Pattern .............................. .............................................................. 8 

3.4 Anticipated Exposure Pathways ............................................... ........................... 9 

3.5 Consideration of Environmental Justice .......................................................... 10 

4.0 Hazard Characterization and Dose-Response Assessment.. ....................................... 10 

4.1 Summary of Toxicological Effects ..................................................................... 10 

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

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

4.2.2 Evidence of Neurotoxicity .................................................................................. 12 

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal .. 12 

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

4.3 Toxicity Endpoint and Point of Departure Selections .......................... ......... .. 13 

4.3.1 Dose-Response Assessment ................................................................................ 13 

4.3.2 Summary of Points of Departure and Toxicity Endpoints Used in Human 

Risk Assessment ......................................................................................... ..................... 14 

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

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

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

5.3 Drinking Water Residue Profile ............................................................ 16 

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

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

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

5.4.3 Acute Dietary Risk Assessment ......................................................... ................ 17 

5.4.4 Chronic Dietary Risk Assessment ..................................................................... 17 

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

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

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................ 18 

6.1 Residential Bystander Post-application Inhalation Exposure ........................ 18 

6.2 Spray Drift ............................................................................................. ......... ..... 19 

7.0 Aggregate Exposure/Risk Characterization ................................................................. 19 

8.0 Cumulative Risk Characterization/ Assessment.. ......................................................... 19 

9.0 Occupational Exposure/Risk Characterization ........ ................................................... 20 

9.1 Short-/Intermediate-Term Handler Risk ......................................................... 20 

9.2 Short-Term Post-Application Risk. ................................................................... 22 

9.2.1 Dermal Post-Application Risk ............................. ,.,.,., ....................................... 22 

9.2.2 Inhalation Post-Application Risk ...................................................................... 22 

10.0 References ........................................................................................................................ 23 

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Appendix A: Physical and Chemical Properties...................................................................... 24

Appendix B: Toxicity Profile and Executive Summaries....................................................... 25

B.1 Toxicology Data Requirements.............................................................................. 25

B.2 Toxicity Profile Tables............................................................................................ 26

B.3 Executive Summaries ............................................................................................. 33

Appendix C: Chemical Name and Structures of Rimsulfuron and Metabolites .................. 36
Rimsulfuron Human Health Risk Assessment DP. No. 408722

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1.0 Executive Summary

Rimsulfuron is a sulfonylurea herbicide that works via inhibition of acetolactate synthase (ALS). 

It is currently registered to E. I. du Pont de Nemours and Co. (DuPont) for use on bushberries, 

caneberries, chickory, soybeans, potatoes, field corn, tomatoes, grapes, various tree fruits, and 

tree nuts for pre- and post-emergence control of annual grasses, broadleaf weeds, and yellow 

nutsedge. Permanent rimsulfuron tolerances are currently established in 40 CFR §180.478. The 

previous risk assessment for rimsulfuron was conducted on May 4, 2012 (D391083, C. Walls,

05/04/12).

DuPont has submitted an application to modify the DuPont Resolve SG Herbicide label (EPA 

Reg. No. 352-748) and the DuPont Steadfast XP Herbicide label (EPA Reg. No. 352-816) to 

include use on ALS tolerant sorghum. 

Use Profile

DuPont Resolve SG Herbicide (EPA Reg. No. 352-748) and DuPont Steadfast XP Herbicide 

(EPA Reg. No. 352-816) end-use products (EPs) are water dispersible granular (WG) 

formulations containing 25% and 15% rimsulfuron by weight, respectively. DuPontTM

Steadfast® XP herbicide (EPA Reg. No. 352-816) also contains the active ingredient (ai) 

nicosulfuron. This assessment addresses the potential exposure and risk of rimsulfuron only. 

Exposure to nicosulfuron from the proposed use on sorghum will be evaluated in a separate 

document. The proposed labels require occupational handlers to wear long pants, long sleeved 

shirts, chemical resistant gloves, shoes, and socks. The restricted entry interval (REI) on the 

proposed labels is 4 hours.

Exposure Profile

There is a potential for occupational short- and intermediate-term inhalation and dermal exposure 

to rimsulfuron during mixing, loading, application, and post-application activities. There is also 

exposure expected through food and drinking water from the proposed and registered uses of 

rimsulfuron. There are no existing or proposed uses for rimsulfuron in residential settings.

Hazard Characterization

For the proposed new use, the toxicological database for rimsulfuron is sufficient for risk 

assessment purposes. All required toxicity studies have been submitted or waived.

The target organs for rimsulfuron are the liver and kidney in the rat and dog, along with the testis 

and blood in the mouse and dog. In the mouse, the stomach was also a target organ. Adverse 

changes in body weight and food consumption were observed in rats, mice, and dogs.

Rimsulfuron has low acute toxicity by the oral, dermal and inhalation routes, but is a moderate 

eye irritant. It is not a dermal sensitizer. Rimsulfuron is not mutagenic and has been classified 

as “Not Likely to be Carcinogenic to Humans,” based on the lack of evidence for carcinogenicity 

in studies conducted in rats and mice. 

There is no quantitative or qualitative evidence of increased susceptibility following pre- and/or 

postnatal exposures in the developmental and reproduction studies, and there are no concerns or 
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residual uncertainties. There was no evidence of neurotoxicity or immunotoxicity in the recently 

submitted studies which have undergone preliminary evaluation and are currently under detailed 

review. Therefore, HED has concluded that the Food Quality Protection Act (FQPA) Safety 

Factor can be reduced to 1X.

An endpoint for acute dietary risk assessment was not selected because there were no adverse 

effects attributable to a single dose. The endpoint for chronic dietary risk assessment was chosen 

from the rat chronic/carcinogenicity study, and was based on liver and body weight 

effects. Incidental oral endpoints were not selected because residential exposures are not 

anticipated. The endpoint for dermal and inhalation risk assessments for occupational workers 

was chosen from the 90-day oral study in the dog, and was based on kidney effects.

Dietary Risk Estimates (Food and Water)

An acute dietary assessment was not performed, as a toxicological endpoint attributable to a 

single dose has not been identified for rimsulfuron.

The chronic dietary (food and drinking water) exposure assessment is considered conservative 

and assumed tolerance-level residues and that 100% of the proposed and registered crops were 

treated with rimsulfuron (100%CT). Dietary Exposure Evaluation Model software with the Food 

Commodity Intake Database (DEEM-FCID) default processing factors were assumed. Estimated 

drinking water concentrations (EDWCs) from ground water from the Environmental Fate and 

Effects Division (EFED) were also included. The results of the chronic analysis indicate that the 

chronic dietary (food and drinking water) risk estimates utilized <1% of the chronic population 

adjusted dose (cPAD) for the general U.S. population and 1.4% of the cPAD for all infants and 

children 1-2 years old, the population subgroups with the highest estimated chronic dietary 

exposure to rimsulfuron. Therefore, the chronic dietary risk estimate is not of concern (i.e., 

<100% of the cPAD). 

Aggregate Risk

Short- and intermediate-term aggregate risk assessments were not performed because there are 

no registered residential uses of rimsulfuron. Therefore, the aggregate risk assessment for 

rimsulfuron only includes chronic exposures to residues in food and drinking water. The chronic 

dietary risk assessments for the U.S. population and all population subgroups are not of concern 

to HED (<100% cPAD).

Occupational Risk

A short- and intermediate-term occupational risk assessment was performed for rimsulfuron 

application using ground and aerial equipment to sorghum; chemigation is not permitted on the

proposed labels. There are no occupational handler risk estimates of concern for the proposed 

uses of rimsulfuron at labeled PPE (baseline + gloves, no respirator). At labeled PPE, all shortand intermediate-term occupational handler combined (dermal + inhalation) MOEs ranged from 

220 to 6,700. The REI on the proposed label is 4 hours. The occupational short-term postapplication risk estimate resulted in a dermal MOE of 3,400 on the day of application and is not 

of concern. Based on the Agency's current practices, a quantitative non-cancer occupational 

post-application inhalation exposure assessment was not performed for rimsulfuron at this time. 

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

quantitative occupational post-application inhalation exposure assessment for rimsulfuron. 
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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).

2.0 HED Recommendations

HED has examined the residue chemistry, toxicity, and exposure databases for rimsulfuron and 

concluded that, provided a revised Section B, a revised Section F are submitted, and a sample of 

the analytical standard, there are no deficiencies that would preclude granting a Section 3 

registration on sorghum. 

The specific tolerance recommendations are discussed in Section 2.2.2. 

2.1 Data Deficiencies

There are no data deficiencies associated with the proposed uses of rimsulfuron.

860.1550 Proposed Tolerances

 The petitioner needs to submit a revised Section F to reflect the correct commodity 

definitions presented in Table 2.2.2.

860.1650 Submittal of Analytical Reference Standards

 The analytical reference standard for rimsulfuron will expire (04/2014). A 5g standard 

needs to be supplied to the repository.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An adequate data collection/enforcement method, the high performance liquid chromatography 

with tandem mass spectroscopy (HPLC/MS/MS) method DuPont-32277, is available for 

determination of residues of rimsulfuron on sorghum commodities. Samples of sorghum 

commodities from the submitted crop field trials were analyzed for residues of rimsulfuron using 

the method. The limit of quantification (LOQ) of the method for sorghum grain, stover, and 

forage is 0.01 ppm. An adequate ILV was conducted with recoveries within the acceptable range 

(70-120%). Radiovalidation data are not needed since the extraction solvent for the method is 

similar to the extraction solvent used in the metabolism studies. This method can be forwarded 

to FDA. Note that rimsulfuron is not recovered by FDA Multiresidue Methods.

2.2.2 Recommended Tolerances 
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Tolerances for residues of rimsulfuron, including its metabolites and degradates, are established 

in 40 CFR §180.478(a). Compliance with tolerance levels specified is to be determined by 

measuring only the parent compound, rimsulfuron. Adequate data, reflecting the proposed use 

pattern, are available for purposes of establishing tolerances in sorghum forage, stover, and 

grain. The available field trial data support the proposed tolerances for residues of rimsulfuron 

on sorghum grain forage, stover, and grain at 0.01 ppm each. The Organisation for Economic 

Co-operation and Development (OECD) statistical calculation procedure was not used to 

determine appropriate tolerance levels since all residues were <LOQ (0.01 ppm).

The proposed use on sorghum does not result in an increased dietary burden to ruminants or

poultry. There is no reasonable expectation of finite residues of rimsulfuron on livestock 

commodities (40 CFR §180.6(a)(3)) based on the registered/proposed uses. The waiver request 

for livestock feeding studies is acceptable. HED notes that if additional uses of rimsulfuron with 

livestock feed items are proposed in the future, livestock feeding studies may be required.

Table 2.2.2. Tolerance Summary for Rimsulfuron.

Commodity Proposed Tolerance 

(ppm)

Recommended 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

Sorghum, forage 0.01 0.01 Sorghum, grain, forage

Sorghum, stover 0.01 0.01 Sorghum, grain, stover

Sorghum, grain 0.01 0.01 Sorghum, grain, grain

2.2.3 Revisions to Petitioned-For Tolerances

Note to PM: The tolerance expression for rimsulfuron should be revised as follows:

Under 40 CFR §180.478(a): “Tolerances are established for residues of the herbicide 

rimsulfuron, including is metabolites and degradates, in or on the commodities in the 

following table [below]. Compliance with the tolerance levels specified in the following 

table [below] is to be determined by measuring only rimsulfuron, N-[[(4,6-dimethoxy-2-

pyrimidinyl)amino]carbonyl]-3-(ethylsulfonyl)-2-pyridinesulfonamide.

2.2.4 International Harmonization 

No Codex or Mexican Maximum Residue Limits (MRLs) have been established for residues of 

rimsulfuron. There are no MRLs established in Canada for rimsulfuron use on sorghum. 

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

The following changes should be made to the proposed labels before granting the 

rimsulfuron use on sorghum:

860.1200 Directions for Use
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 The labels should indicate that application should be made to “grain sorghum” rather than 

to “sorghum”.

 Subsequent to completion of the residue chemistry summary document, the registrant 

proposed amending the preharvest intervals (PHI) to plant height and growth stages. The 

proposed change is consistent with the residue data and HED has no objections to the 

proposed PHI. The PHI changes supersede those mentioned in the residue chemistry 

review.

3.0 Introduction

Rimsulfuron is a sulfonylurea herbicide that works via inhibition of ALS. Inhibition of the 

enzyme leads to rapid cessation of plant growth and visual symptoms such as chlorosis, necrosis, 

leaf malformation and discoloration. These effects appear a few days after treatment in sensitive 

species. ALS is not found in humans or mammals. 

3.1 Chemical Identity

Table 3.1. Rimsulfuron Nomenclature.

Compound

Common name Rimsulfuron

Company experimental name DPX-E9636

IUPAC name 1-(4,6-dimethoxypyrimidin-2-yl)-3-(3-ethylsulfonyl-2-pyridylsulfonyl)urea

CAS name N-[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]-3-(ethylsulfonyl)-2-

pyridinesulfonamide

CAS registry number 122931-48-0

3.2 Physical and Chemical Properties

The physical/chemical properties of rimsulfuron are summarized in Appendix A. Based on the 

molecular weight, low vapor pressure (7.5 x 10-8 mm Hg at 25o C) and KOW (<0.0342 at pH 7), 

rimsulfuron is not expected to volatilize, pass lipid barriers, or bioaccumulate.

3.3 Pesticide Use Pattern

Rimsulfuron is currently registered to DuPont for use on bushberries; caneberries; chickory; field 

corn; grapes; potatoes; soybeans; tomatoes; and various tree fruits and tree nuts; for pre- and 

post-emergence control of annual grasses, broadleaf weeds, and yellow nutsedge. DuPont 

submitted a petition to allow rimsulfuron use on sorghum tolerant to ALS herbicides. When 

applied to sorghum resistant to ALS-inhibitors, the surrounding weeds will be controlled. 

However, when applied to sorghum that is not resistant to ALS-inhibitor herbicides, the plant 

N S

O

N

O H

N

H

O N

N OCH3

OCH3

SO2C2H5
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itself will be eliminated. Rimsulfuron has no registered residential uses. The formulations 

relevant to the sorghum use request are formulated EP labels DuPontTM Steadfast® XP herbicide, 

(EPA Reg. No. 352-816) and DuPont Resolve SG Herbicide (EPA Reg. No. 352-748). Both 

formulated end-use products are WG formulations containing 15% and 25% rimsulfuron by 

weight, respectively. The proposed use on sorghum is summarized in Table 3.3. 

Table 3.3 Summary of Directions for Use of Rimsulfuron. 

Application 

Timing; Type; 

Equipment

Formulation

[EPA Reg. 

No.]

Use Rate

(lb ai/A)

Max. 

Uses per 

Season

RTI 

(days)

Max. 

Seasonal 

Use Rate

(lb ai/A)

PHI

(Days)

Use Directions and 

Limitations1

Sorghum Containing the DuPontTM INZENTM Z Tolerance Trait

Post-emergence

Aerial

Ground

DupontTM 

Resolve®

25% DF

[352-748]

1.0-2.0 oz/A

(0.016-0.031)

2

(7-days)

2.0 oz/A

(0.031)

Mature 

Stage 

(forage, 

grain, 

stover)

Application is to be made to 

emerged sorghum that is up 

to 20 inches tall. Applications 

made to 4-20 inch tall 

sorghum (V3-V7 stage) are 

recommended for best weed 

control and crop tolerance. 

Best results are obtained 

when applications are made 

to young actively growing 

weeds. Do not apply to 

sorghum taller than 20 

inches. 

Use of a spray adjuvant is 

required (NIS at 0.25%-0.5% 

v/v, or COC at 1%-2% v/v, or 

a combination adjuvant 

containing NIS, COC, MSO 

and/or ammonium nitrogen 

fertilizer). For aerial 

application using COC use at 

0.5% v/v

DupontTM 

Steadfast

XP Herbicide

15% 

Rimsulfuron

[352-816]

1.25-1.67 

oz/A

(0.012-0.016)

1.67 oz/A

(0.016)

1 NIS = Nonionic Surfactant; COC = Crop Oil Concentrate; MSO = Methylated Seed Oil. 

Subsequent to completion of the residue chemistry summary document, the registrant proposed 

amending the preharvest intervals (PHI) to plant height and growth stages. The proposed change 

is consistent with the residue data and HED has no objections to the proposed PHI. The PHI 

changes supersede those mentioned in the residue chemistry review.

3.4 Anticipated Exposure Pathways

Humans may be exposed to rimsulfuron in food and drinking water, since rimsulfuron may be 

applied directly to growing crops and application may result in rimsulfuron reaching surface and 

ground water sources of drinking water. In an occupational setting, applicators may be exposed 

while handling the pesticide prior to application, as well as during application. There is a 

potential for post-application exposure for workers re-entering treated fields. This risk 

assessment considers all of the aforementioned exposure pathways based on the proposed new 
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uses of rimsulfuron, but also considers the existing uses as well, particularly for the dietary 

assessment.

3.5 Consideration of Environmental Justice

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

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

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

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

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

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

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

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

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

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

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

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

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

and exposure assessments are performed when conditions or circumstances warrant. Whenever 

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

for adult applicators and for children 1-2 years, youths, and adults entering or playing on treated 

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

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

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

patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

Rimsulfuron is a sulfonylurea herbicide that works via inhibition of acetolactate synthase (ALS) 

an enzyme found in plants and micro-organisms. The relevance of this mode of action to 

humans has not been established.

4.1 Summary of Toxicological Effects

The toxicity database indicates that target organs for rimsulfuron are the liver and kidney in the 

rat and dog, along with the testis and blood in the mouse and dog. In the mouse, the stomach 

was also a target organ. Adverse changes in body weight and food consumption were observed in 

rats, mice and dogs. 

In subchronic toxicity studies in rats, decreased body weight, body weight gain, increased 

relative liver and absolute kidney weights, and diuresis were observed; in the dog subchronic 

study decreased liver enzymes and bilirubin, fatty change, and hepatocellular hypertrophy were 

observed. In chronic rat studies, decreased body weight gain, and increased liver weights were 

observed in both sexes, with increased mortality at higher dose levels in males. In a subchronic 

study in mice, increased red blood cell (RBC) and hemoglobin, and decreased body weight gain 

and food efficiency were observed. After mouse chronic exposure, decreased body weight, 
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increased incidences of dilation and cysts in the glandular stomach, and degeneration of the 

testicular artery and tunica albuginea were observed. In dogs, diuresis indicated by increased 

urinary volume, platelet concentration and kidney weights accompanied by decreased urinary 

osmolality was observed after 90 days. Chronic exposure led to increased absolute liver and 

kidney weights and increased incidence of seminiferous tubule degeneration and increased 

numbers of spermatid giant cells present in epididymides in males at in males, while in both 

sexes decreased mean body weight and body weight gain, increased serum cholesterol levels and 

alkaline phosphatase activity, increased absolute liver weight, and increased relative liver and 

kidney weights were observed.

In the developmental toxicity study in rats, no developmental toxicity was seen at the highest 

dose tested. In the developmental toxicity study in rabbits (in which both maternal and fetal 

death were observed), and in the two-generation study in rats (in which decreases in body weight 

gain were observed in both parents and offspring, developmental and offspring effects were seen 

in the presence of maternal/systemic toxicity at the same dose levels. Consequently, there is no 

evidence of quantitative or qualitative increased susceptibility following pre- and/or postnatal 

exposures and there are no concerns or residual uncertainties.

Rimsulfuron did not demonstrate neurotoxicity in the acute or subchronic neurotoxicity studies, 

nor did it suppress the immune response in the immunotoxicity study.

HED classified rimsulfuron as “Not Likely to be Carcinogenic to Humans” based on the lack of 

evidence for carcinogenicity in rats and mice in the long term carcinogenicity studies. 

Rimsulfuron is not considered to be a mutagen or clastogen. It has low acute oral, dermal and 

inhalation toxicity, but is a moderate eye irritant. It is not a dermal sensitizer.

In standard metabolism studies, there were no remarkable differences in the excretion pattern of 

either males or females in the low, high or repeat dose groups. Within the first 72 hours, greater 

than 90% of the administered radioactivity was excreted. Urinary elimination predominated, 

accounting for approximately 64% of the dose; approximately 30% was eliminated in the feces. 

Monitoring of the expired air indicated that less than 0.08% of the radiolabel was present in 

expired CO2. For all of the treatment groups, 93 to 96% of the radioactivity administered was 

recovered in either the feces (20 to 33%) or urine (58 to 67%). After 72 hours, the animals were 

sacrificed and the tissue distribution of labeled residues was determined. Low, but detectable 

amounts of radioactivity were found in the heart, lung, liver, kidney, and muscle; animals in the 

repeat dose groups also showed some accumulation in the spleen. Hepatic accumulation, 

although low, was slightly higher than other organs; within each treatment group, the males 

showed more accumulation in the liver than the females. The metabolic profiles were 

determined on pooled urinary and fecal samples. The highest percentage of the urinary (42 to 

55%) and fecal (5 to 16%) radioactivity was attributed to unmetabolized parent compound. 

Metabolism largely involved either the contraction or cleavage of the sulfonylurea bridge. 

Following contraction of the sulfonylurea bridge, demethylation to metabolite P5 and subsequent 

hydroxylation to metabolite P4 occurred. Data on enzymatic (β-glucuronidase) or acid hydrolysis 

were not presented. Therefore, the contribution of Phase II biotransformation reactions to the 

detoxification of DPX-E9636 could not be assessed.
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No dermal absorption or dermal toxicity data are available for this chemical, and the dermal 

absorption factor of 100% is used for risk assessment.

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

The rimsulfuron database is considered complete and sufficient for risk assessment. There are 

no concerns for neurotoxicity or susceptibility, and there are no residual uncertainties in the 

exposure database. Therefore, HED determined that the FQPA SF can be reduced to 1x. 

4.2.1 Completeness of the Toxicology Database

The toxicity database for rimsulfuron is considered to be complete and sufficient for endpoint 

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

FQPA, and an additional database uncertainty factor does not need to be applied.

The required inhalation toxicity study for rimsulfuron has been waived based on rimsulfuron’s 

use pattern (MOEs > 4,400), physical chemical properties, low acute inhalation toxicity, and a 

lack of evidence that a point of departure (POD) from a subchronic inhalation toxicity study 

would be more protective than the available POD from an oral study for inhalation risk 

assessment. (K. Rury, TXR#0056438, 09/17/2012). In absence of a route specific inhalation 

toxicity study, a POD for inhalation exposure risk assessment as been extrapolated from an oral 

study.

4.2.2 Evidence of Neurotoxicity

An acute neurotoxicity study was conducted in rats at dose levels up to 2000 mg/kg. No 

significant adverse effects on neurologic tissue or function were observed. Functional 

observation battery, motor activity, gross and microscopic pathology, all failed to show an 

increased incidence of adverse effects that could be related to treatment. The neurotoxicity 

lowest observed adverse effect level (LOAEL) was not established. The no observed adverse 

effect level (NOAEL) was 2000 mg/kg, the highest dose level in the study, and the limit dose.

A subchronic neurotoxicity study was conducted in rats at dose levels up to 7500 ppm (438/507 

mg/kg/day in Males/Females). There were no treatment related effects on mortality, clinical 

signs, body weight, brain weight or gross and histologic pathology or neuropathology. 

Functional operational battery (FOB) and motor activity testing revealed no treatment-related 

effects. The LOAEL was not established. The NOAEL was 7500 ppm, equivalent to 438 and 507 

mg/kg/day in males and females, respectively.

The available neurotoxicity battery, therefore, did not raise concern for neurotoxicity. Similarly, 

the subchronic and chronic data in the database did not show any adverse effects that could be 

considered as neurotoxicity.

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal
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In the developmental toxicity study in rats, no developmental toxicity was seen at the highest 

dose tested. In the developmental toxicity study in rabbits, and in the two generation study in 

rats, developmental and offspring toxicity (see Section 4.3) were seen only in the presence of 

maternal/systemic toxicity. Consequently, there is no evidence of quantitative or qualitative 

increased susceptibility following pre- and/or postnatal exposures.

4.2.4 Residual Uncertainty in the Exposure Database

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

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

the exposure estimates are underestimated. The chronic dietary assessment utilized tolerancelevel residues for all crops. In addition, default processing factors were incorporated into the 

assessment, and 100% crop treated was assumed for all commodities. The DEEM analysis also 

assumed that all drinking water will contain rimsulfuron at the highest EDWC levels modeled by 

EFED for groundwater or surface water. For these reasons it can be concluded that the dietary 

exposure analysis does not underestimate risk from chronic exposure to rimsulfuron. 

4.3 Toxicity Endpoint and Point of Departure Selections

4.3.1 Dose-Response Assessment

Endpoint selection and points of departure have been presented in a previous risk assessment (E. 

Holman, D384623, 11/04/11), and are summarized in Table 4.3.4.

For acute dietary exposure, there were no toxicological effects attributable to a single dose 

observed in oral toxicity studies including the acute neurotoxicity study in rats (currently under 

review) and developmental toxicity studies in rats and rabbits. Therefore, a dose and endpoint 

were not selected for this risk assessment.

For chronic dietary exposure, the rat chronic/carcinogenicity study was selected for risk 

assessment because the NOAEL from that study represents the lowest available NOAEL for 

effects of rimsulfuron following long-term dietary administration, and is protective of all other 

toxic effects seen in the existing database. The study is appropriate for chronic dietary exposure 

due to the route (oral) and long-term duration of dosing. Chronic mouse and dog studies were 

also considered for chronic dietary exposure; however, the chronic rat study provided the most 

sensitive endpoints for chronic dietary risk assessment.

No residential exposures are anticipated for the projected use patterns, so residential risk 

assessments were not conducted.

For short- and intermediate-term dermal and inhalation exposures, in the absence of routespecific data, the subchronic oral toxicity study in dogs was used for dermal risk assessment. The 

selected endpoint provides the most sensitive NOAEL available from a study of appropriate 

duration, i.e. subchronic. Since the endpoint for risk assessment was selected from an oral study, 

a dermal absorption value of 100% was used for route-to-route extrapolation in the risk 
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assessment, and equivalent toxicity via the inhalation and oral routes was assumed for the 

purpose of route-to-route extrapolation. In the subchronic dog study, the minimal effects seen at 

the LOAEL, increased urinary volume, kidney weights, and decreased osmolality, are supported 

by the observations that the kidney is a target organ in rats and dogs (increased kidney weights, 

diueresis) following rimsulfuron exposure; also, other sulfonylurea compounds in the HED 

Integrated Structure, Toxicity, Endpoints and Properties (iSTEP) database produce kidney effects 

such as nephropathy, kidney weight changes and atrophy in subchronic, chronic and multigeneration reproduction studies. Therefore, the study and endpoint used for short- and 

intermediate-term dermal and inhalation exposures are considered appropriate for risk 

assessment.

The dog subchronic study used for short- and intermediate-term dermal and inhalation exposures

provides a lower NOAEL than the rat chronic rat study used for the Chronic RfD. However, the 

LOAELs for both studies, 120 mg/kg/day for the rat study versus 125 mg/kg/day are very 

similar, suggesting that the difference in NOAELs may just be a matter of dose selection, and 

thus not toxicologically significant.

4.3.2 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment

Table 4.3.4 Summary of Toxicological Doses and Endpoints for Rimsulfuron for Use in Dietary, NonOccupational, and Occupational Human Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/FQP

A Safety Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(All 

Populations)

An appropriate endpoint attributable to a single dose was not identified.

Chronic 

Dietary (All 

Populations)

NOAEL= 

11.8 mg/kg 

bw/day

UFA=10x

UFH=10x

FQPA SF=1x

Chronic RfD 

= 0.118

mg/kg/day

cPAD = 

0.118 

mg/kg/day

Combined Chronic/Carcinogenicity-Rat 

LOAEL= 121 mg/kg/day in males; 

568mg/kg/day in females (NOAEL=163 

mg/kg/day), based on decreased body 

weight gains and liver effects. 

Incidental 

Oral ShortTerm (1-30 

days);

IntermediateTerm (1-6 

months) 

Use pattern does not indicate a need for this risk assessment.

Dermal ShortTerm (1-30 

days);

IntermediateTerm (1-6 

months)

NOAEL= 

6.25 mg/kg 

/day

UFA=10x

UFH=10x

DAF=100%

Occupational 

LOC for 

MOE = 100

90 Day Toxicity-Dog

LOAEL=125 mg/kg/day, based on 

increased urinary volume, kidney 

weights, and decreased osmolality.
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Table 4.3.4 Summary of Toxicological Doses and Endpoints for Rimsulfuron for Use in Dietary, NonOccupational, and Occupational Human Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/FQP

A Safety Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Inhalation 

Term (1-30 

days);

IntermediateTerm (1-6 

months)

NOAEL= 

6.25 mg/kg 

/day

UFA=10x

UFH=10x

Occupational 

LOC for 

MOE = 100

90 Day Toxicity-Dog

LOAEL=125 mg/kg/day, based on 

increased urinary volume, kidney 

weights, and decreased osmolality.

Cancer (oral, 

dermal, 

inhalation)

Rimsulfuron is considered “not likely to be carcinogenic to humans” due to the absence of 

tumors in rat and mouse carcinogenicity studies.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to 

mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL 

= no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = 

extrapolation from animal to human (intraspecies). UFH = potential variation in sensitivity among members of the human 

population (interspecies). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = 

reference dose. DAF=Dermal absorption factor. Inhalation toxicity considered to be equivalent to toxicity via the oral route. 
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5.0 Dietary Exposure and Risk Assessment

5.1 Residues of Concern Summary and Rationale

The residue of concern for enforcement and risk assessment is the parent compound, 

rimsulfuron. The residues of concern for drinking water include parent rimsulfuron and all 

major degradates which maintain the sulfonylurea bridge which include degradates identified as 

IN-70941 and IN-70942 (structures listed in Appendix C). Therefore, the total residue method 

will be used to estimate exposure in drinking water sources.

Table 5.1. Compounds to be Included in the Rimsulfuron Risk Assessment and Tolerance Expression.

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Plants Primary Crop Rimsulfuron Rimsulfuron

Rotational Crop Rimsulfuron Rimsulfuron

Livestock Ruminant Rimsulfuron Rimsulfuron

Poultry Rimsulfuron Rimsulfuron

Drinking Water Rimsulfuron, IN-70941 and 

IN-70942

Not Applicable

5.2 Food Residue Profile

Permanent tolerances have been established under 40 CFR §180.478(a) for residues of 

rimsulfuron at 0.01 ppm in/on citrus fruit, pome fruit, stone fruit, grapes, tree nuts, pistachios

caneberry and bushberries; 0.05 ppm in/on tomatoes, 0.09 ppm in/on almond hulls, 0.1 ppm 

in/on field corn grain, forage, and stover; chicory (roots and tops) is 0.01 ppm. The proposed 

tolerance associated with the new uses of rimsulfuron on sorghum grain, forage, and stover is 

0.01 ppm. Based on the registered/proposed ruminant feed items, there is no reasonable 

expectation of finite residues of rimsulfuron in livestock commodities. Adequate field trial and 

storage stability data are available to support the established/recommended tolerances.

5.3 Drinking Water Residue Profile

The drinking water residues used in the dietary risk assessment were provided EFED (M. Barrett, 

D414506, 03/13/2014). Water residues were incorporated directly into the DEEM-FCID 

assessment under the food categories “water, direct, all sources” and “water, indirect, all 

sources.” 

Rimsulfuron foliar applications using ground and aerial sprays impact both surface and ground 

water drinking water sources given that it possesses similar physical chemical properties and 

persistence to other chemicals which are known to translocate to these media.

The estimate is based on assessment of all registered uses using the Tier 1 model PRZM-GW 

(Pesticide Root Zone Model-Ground Water). The models and their descriptions are available at 
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the EPA internet site: http://www.epa.gov/oppefed1/models/water/. The maximum estimated 

drinking water concentrations (EDWCs) are presented below in Table 5.3.

In this updated drinking water exposure assessment it has been determined that exposure from 

the current and proposed uses should not exceed 22.2 μg/L (ppb) for acute exposure and 19.7 

μg/L (ppb) for chronic and cancer exposure. The values in Table 5.3 are based on uses from 

several crop sites with higher single and seasonal maximum application rates than proposed for 

the new use on ALS inhibitor tolerant sorghum. These values reflect a predicted higher potential 

exposure level from groundwater sourced drinking water supplies than surface water supplies.

 

Table 5.3. Maximum Tier I Rimsulfuron ROC EDWCs for Drinking Water Based on Application to 

Crops with Highest Rates and Exposure Potential.

Crops (scenario)

Highest Daily Value

(Acute)

Post-Breakthrough Average 

(Chronic and Cancer)

All 22.2 19.7

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

Existing and recommended tolerance-level residues [40 CFR §180.478(a)] have been used for all 

food commodities in this assessment. Permanent tolerances are established for residues of 

rimsulfuron at levels ranging from 0.01 ppm to 4.5 ppm. For the proposed new use on sorghum, 

a tolerance level of 0.01 ppm is recommended (D418153, M. Negussie, 03/17/2014).

DEEMTM Version 7.81 default processing factors were applied to all processed commodities for 

which they were available. In the processing study for soybean oil, residues did not concentrate. 

Therefore, the processing factor was left at 1.0. 

5.4.2 Percent Crop Treated Used in Dietary Assessment

It was assumed that 100% of foods in the assessment had residues of rimsulfuron (i.e., 100% 

crop treated). 

5.4.3 Acute Dietary Risk Assessment

No acute dietary toxicity endpoint could be identified based on the toxicology data currently 

available for rimsulfuron; therefore, an acute assessment was not performed. 

5.4.4 Chronic Dietary Risk Assessment

The chronic dietary (food and drinking water) exposure assessment is considered conservative 

and unrefined. The results of the chronic analysis indicate that the chronic dietary (food and 

drinking water) risk estimates utilized <1% of the cPAD for the general U.S. population and 

1.4% of the cPAD for all infants and children 1-2 years old, the most highly exposed population 

subgroup. Therefore, the chronic dietary risk is not of concern (i.e., <100% of the cPAD). 
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5.4.5 Cancer Dietary Risk Assessment

Rimsulfuron is classified as “Not Likely to be Carcinogenic to Humans”; therefore, a cancer 

dietary exposure assessment was not performed. 

5.4.6 Summary Table

Table 5.4.6. Chronic Aggregate Dietary (Food + Drinking Water) Exposure and Risk for Rimsulfuron

Population Subgroup Exposure

(mg/kg/day) % cPAD

General U.S. Population 0.000807 <1

All Infants (< 1 year old) 0.001710 1.4

Children 1-2 years old 0.001658 1.4

Children 3-5 years old 0.001473 1.2

Children 6-12 years old 0.001002 <1

Youth 13-19 years old 0.000724 <1

Adults 20-49 years old 0.000743 <1

Adults 50-99 years old 0.000652 <1

Females 13-49 years old 0.000724 <1

1The population subgroup with the highest estimated chronic dietary (food + drinking water) exposure and risk is

indicated by bold text.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no proposed residential uses for rimsulfuron, therefore a non-occupational exposure 

assessment was not conducted.

6.1 Residential Bystander Post-application Inhalation Exposure

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

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

inhalation toxicity (Toxicity Category IV), low vapor pressure (7.5x10-8 mm Hg at 25 oC), and 

the low proposed use rate (0.031 lb ai/A). However, volatilization of pesticides may be a source 

of post-application inhalation exposure to individuals nearby pesticide applications. The Agency 

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

Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, 

and received the SAP’s final report on March 2, 20101. The Agency is in the process of 

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

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

 

1 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
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the Agency's risk assessments. If new policies or procedures are developed, the Agency may 

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

rimsulfuron.

6.2 Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is 

particularly the case with aerial application, but, to a lesser extent, spray drift can also be a 

potential source of exposure from the ground application methods (e.g., groundboom and 

airblast) employed for rimsulfuron. The Agency has been working with the Spray Drift Task 

Force (a task force composed of various registrants which was developed as a result of a Data 

Call-In issued by EPA), EPA Regional Offices and State Lead Agencies for pesticide regulation 

and other parties to develop the best spray drift management practices (see the Agency’s Spray 

Drift website for more information). 2 The Agency is also taking means to qualitatively and 

qualitatively address spray drift as a potential source of exposure in risk assessments for 

pesticides through existing programs such as Ag Drift and chemical specific properties of 

pesticides. The potential for spray drift will be quantitatively evaluated for each pesticide during 

the Registration Review process which ensures that all uses for that pesticide will be considered 

concurrently. 

7.0 Aggregate Exposure/Risk Characterization

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

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

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

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

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

duration of exposure.

An acute aggregate risk assessment was not performed because no appropriate endpoint was 

available to determine the aRfD for the general U.S. population or any population subgroup. 

There are no residential uses of rimsulfuron. Therefore, the aggregate risk assessment for 

rimsulfuron only includes chronic exposures to residues in food and drinking water. The chronic 

dietary risk assessments for the U.S. population and all population subgroups are not of concern 

to HED (<100% cPAD). The results of the chronic analysis indicate that the chronic dietary 

(food and water) risk estimates utilized <1.0% of the cPAD for the general U.S. population and 

1.4% of the cPAD for all infants and children 1-2 years old, the most highly exposed population 

subgroups. 

8.0 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 

rimsulfuron and any other substances, and rimsulfuron does not appear to produce a toxic 

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

 

2 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
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assumed that rimsulfuron does not have a common mechanism of toxicity with other substances. 

For information regarding EPA’s efforts to determine which chemicals have a common 

mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy 

statements released by EPA’s Office of Pesticide Programs concerning common mechanism 

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

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

9.0 Occupational Exposure/Risk Characterization

There is potential for short- and intermediate-term occupational exposure to rimsulfuron during 

both handler [mixing, loading, and application (via the dermal and inhalation routes)] and postapplication activities (via the dermal route) based on the proposed uses. 

9.1 Short-/Intermediate-Term Handler Risk

HED has evaluated occupational exposure from the proposed uses of rimsulfuron. Application 

methods, maximum application rates, and use sites are summarized in Table 3.3. Chemigation 

application is prohibited on the proposed labels; however, rimsulfuron may be applied with aerial 

and ground equipment. Based on application rate and label information, only short- and 

intermediate-term exposure is expected for occupational handlers. However, for both dermal and 

inhalation exposures, the PODs selected are considered protective of both durations. The 

proposed labels require occupational handlers to wear long pants, long sleeved shirts, chemical 

resistant gloves, shoes, and socks. 

HED’s LOC for the MOE is defined by the uncertainty factors that are applied to the assessment. 

HED applies a 10X factor to account for variability among species and a 10X factor to account 

for variability within species. The total uncertainty factor that has been applied to the handler 

assessment of rimsulfuron is 100X for occupational exposure. Occupational exposure and risk 

resulting in MOEs greater than or equal to 100 will not be of concern to HED. Dermal and 

inhalation risk estimates were combined in this assessment, since the toxicological effects and 

PODs chosen for these exposure routes are the same. 

A summary of the short-term dermal and inhalation risk estimates for occupational handlers 

applying rimsulfuron is provided in Table 9.1. There are no risk estimates of concern for the 

proposed uses of rimsulfuron at labeled PPE (baseline + gloves, no respirator). At labeled PPE, 

all short- and intermediate-term occupational handler combined (dermal + inhalation) MOEs 

ranged from 220 to 6,700. 
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Table 9.1. ST and IT Occupational Handler Exposure and Risk Estimates for Rimsulfuron 

Exposure Scenario Crop

Dermal Unit 

Exposure

(μg/lb ai)1

Inhalation Unit 

Exposure

(μg/lb ai)1

Maximum 

Application 

Rate2

(lb ai/A)

Area

Treated 

Daily3

(A/day)

Dermal Inhalation Total

Baseline + Gloves Baseline 

(no respirator)

Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

Mixer/Loader

Aerial (SG form.) Sorghum 51.6 8.96 0.031 1200 0.024 260 0.0042 1,500 220

Groundboom (SG form.) 51.6 8.96 0.031 200 0.0040 1,600 0.00070 9,000 1,400

Applicator

Aerial (liquid form.) Sorghum 2.08 0.0049 0.031 1200 0.00094 6,700 0.0000022 2,800,000 6,700

Groundboom (liquid form.) 16.1 0.34 0.031 200 0.0013 5,000 0.000027 240,000 1,000

Flagger

Flagger Sorghum 12.0 0.35 0.031 350 0.0016 3,800 0.000048 130,000 3,800

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table”

2 Based on registered or proposed label (Reg. No. 352-748 and 352-816).

3 Exposure Science Advisory Council Policy #9.1.

4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A/day) × DAF (100%) ÷ BW (80 kg).

5 Dermal MOE = Dermal NOAEL (6.25 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

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

7 Inhalation MOE = Inhalation NOAEL (6.25 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

8 Total MOE = NOAEL (6.25 mg/kg/day) ÷ Dermal Dose + Inhalation Dose.
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9.2 Short-Term Post-Application Risk

9.2.1 Dermal Post-Application Risk

Rimsulfuron is applied as a postemergence spray to control weeds in sorghum. Common postapplication activities performed on commercially grown sorghum fields are scouting and hand 

weeding which have the potential for dermal exposure to workers performing such activities. 

However, hand weeding would not be necessary following application of an herbicide. 

Therefore, only dermal exposures during scouting activities were assessed. Although short- and 

intermediate-term exposures could occur for the proposed use rimsulfuron on sorghum, since the 

POD is the same for dermal short- and intermediate-term exposures, one assessment is protective 

of both durations. 

Chemical-specific dislodgeable foliar residue (DFR) data have not been submitted for

rimsulfuron. Therefore, this assessment uses HED’s default assumption that 25% of the 

application is available for transfer on day 0 following the application and the residues dissipate 

at a rate of 10% each following day. A DFR study is not required for rimsulfuron at this time 

since the dermal MOEs are greater than 4 times the LOC based on default values for the fraction 

of application rate available for transfer after a foliar application.

The occupational short-term post-application risk assessment resulted in a dermal MOE of 3,400 

on the day of application. Therefore, there are no post-application risk estimates of concern for 

rimsulfuron. 

Table 9.2 presents the results of the occupational post-application risk assessment when HED 

default assumptions are used. Using surrogate data, the dermal MOEs from agricultural postapplication activities are greater than 100 and are not of concern.

Table 9.2. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Rimsulfuron.

Crop/Site Activities Transfer Coefficient 

(cm2/hr) DFR1 Dermal Dose (mg/kg/day)2 MOE3

Short- and Intermediate- term

Sorghum Scouting 210 0.0869 0.0018 3,400

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

2 Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (100%)]  BW (80kg).

3 MOE = POD (6.5 mg/kg/day) / Daily Dermal Dose. 

9.2.2 Inhalation Post-Application Risk

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

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

inhalation toxicity (Toxicity Category IV), low vapor pressure (7.5 x 10-8 mm Hg at 25oC), and 

the low proposed use rate (0.031 lb ai/A). However, there are multiple potential sources of postapplication inhalation exposure to individuals performing post-application activities in 
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previously treated fields. These potential sources include volatilization of pesticides and 

resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert 

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

Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and 

received the SAP’s final report on March 2, 20103. The Agency is in the process of evaluating 

the SAP report as well as available post-application inhalation exposure data generated by the 

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

subsequently, the way to incorporate occupational post-application inhalation exposure into the 

Agency's risk assessments. If new policies or procedures are put into place, the Agency may 

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

for rimsulfuron.

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

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

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

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

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

inhalation exposure scenarios.

10.0 References

M. Barrett. 03/13/14. D414506. Tier I Drinking Water Assessment for the proposed Section 3 

ALS inhibition tolerant sorghum crops new use for the chemical Rimsulfuron (P.C. Code: 

129009, DP Barcode 414506).

M. Negussie. 03/17/14. D394389. Rimsulfuron Chronic Aggregate Dietary (Food and Drinking 

Water) Exposure and Risk Assessment for the Section 3 Registration on Acetolactase Synthase 

(ALS) Tolerant Grain Sorghum. 

M. Negussie. 03/17/14. D418153. Rimsulfuron. Petition for the Establishment of Permanent 

Tolerances for Uses on Acetolactase Synthase (ALS) Tolerant Grain Sorghum. Summary of 

Analytical Chemistry and Residue Data.

C. Walls. 05/04/12. D391083. Rimsulfuron. Human Health Risk Assessment for Proposed 

Section 3 Use on Chicory. 

C. Walls. 05/04/12. D418152. Rimsulfuron: Occupational and Residential Exposure 

Assessment for the New Use on ALS-Tolerant “DuPont INZEN Z” Sorghum.

 

3 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
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Appendix A: Physical and Chemical Properties

Table A.1. Physicochemical Properties of Rimsulfuron

Parameter Value Reference

Melting point 176-178C Reviewed in DP# 193018, M. 

Nelson, 23/NOV/1993; All 

product chemistry 

requirements reported to be 

fulfilled.

Also, MRID No. 47572805.

pH 4.32 to 5.89 (1% dilution in water)

Density 0.784 ± 0.0016 g/mL

Water solubility pH 5: 0.135 ± 0.005 g/L (25°C)

pH 7: 7.3 ± 0.03 g/L (25C)

pH 9: 5.56 ± 0.05 g/L (25C)

pH 4-4.5: 0.024 ± 0.001 g/L (20C)

Solvent solubility (25°C) N,N-dimethylformamide 241 ± 1 g/L

Dimethyl sulfoxide 113 ± 3 g/L

Methylene chloride 35.5 ± 0.4 g/L

Acetonitrile 17.2 ± 0.5 g/L

Acetone 14.8 ± 0.5 g/L

Ethyl acetate 2.85 ± 0.17 g/L

Methanol 1.55 ± 0.11 g/L

Toluene 0.363 ± 0.022 g/L

Xylenes 0.093 ± 0.008 g/L

n-Hexane <0.01 g/L

Vapor pressure (25°C) <10-5 Pa; 7.5x10-8mmHg

Dissociation constant, pKa 4

Octanol/water partition coefficient, 

Log(KOW)

pH 5: 1.94

pH 7: 0.0342

pH 9: not attempted

UV/visible absorption spectrum pH 1.80 at 230 nm, ε = 1.78 x 104(log ε = 4.25) 

and at 290 mm, ε = 1.81x 102(log ε = 2.26)

pH 2.10 at 290 nm, ε = 2.03 x102(log ε = 2.31)

pH 5.03 at 240 nm, ε = 2.24 x 104(log ε = 4.35) 

and at 290 nm, ε = 4.81 x 102(log ε = 2.68)
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Appendix B: Toxicity Profile and Executive Summaries

B.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for Food Use for Rimsulfuron are in the following table. 

Use of the new guideline numbers does not imply that the new (1998) guideline protocols were 

used.

Study Technical

Required Satisfied

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

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

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

870.2400 Primary Eye Irritation....................................................

870.2500 Primary Dermal Irritation..............................................

870.2600 Dermal Sensitization .....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)...............................................

870.3150 Oral Subchronic (nonrodent).........................................

870.3200 21-Day Dermal..............................................................

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

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

yes

yes

no

no

no

yes

yes

waived

--

waived

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

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

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)..............................................

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

870.4200a Oncogenicity (rat)..........................................................

870.4200b Oncogenicity (mouse) ...................................................

870.4300 Chronic/Oncogenicity ...................................................

no

yes

no

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial.....................

870.5300 Mutagenicity—Gene Mutation - mammalian................

870.5375 Mutagenicity—Chromosomal Aberrations ...................

870.5395 Mutagenicity—In Vivo micronucleus...........................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotox. (hen).....................................

870.6100b 90-Day Neurotoxicity (hen) ..........................................

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

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

870.6300 Develop. Neuro .............................................................

no

no

yes

yes

no

--

--

yes

yes

--

870.7485 General Metabolism ......................................................

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

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

yes

no

yes

yes

--

yes

Special Studies for Ocular Effects

Acute Oral (rat)...........................................................

Subchronic Oral (rat)..................................................

Six-month Oral (dog)..................................................

no

no

no

--

--

--
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B.2 Toxicity Profile Tables

Table A.2.1 Acute Toxicity Profile – Rimsulfuron

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral Rat

Acute oral Mouse

41356311 

41356310

41931634

41931623

LD50 = > 5000 

mg/kg

LD50 = > 5000 

mg/kg

IV

IV

870.1200 Acute dermal Rabbit 41356312 

41356313 

41931624

41931635

LD50 = > 2000

mg/kg IV

870.1300 Acute inhalation Rat 41356314 

41931625

41931637

41931636

LC50 = >5.4; > 

5.0; > 7.5; > 5.4

mg/L

IV

870.2400 Acute eye irritation Rabbit 41931626 

41356315 

41356316 

41931638

Moderate eye 

irritant

III

870.2500 Acute dermal irritation Rabbit 41931627

41356318

41931639 

41356317 

No irritation IV

870.2600 Skin sensitization Guinea Pig 41931628 

41356320 

41931641 

41931640

41356319

Not a sensitizer IV
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Table B.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No./ Study 

Type

MRID No. (year)/ Classification /Doses Results

870.3100

90-Day oral toxicity 

(rat)

41356321 (1989)

0, 50, 1500, 7500, 2000 ppm

0, 2.5, 75, 375, 1000 mg/kg bw/day

Acceptable-Guideline

NOAEL = 75 mg/kg bw/day

LOAEL = 375 mg/kg bw/day based on 

reduced body wt. gains.

870.3100

90-Day oral toxicity 

(mouse)

41356323 (1989)

(90-day oral toxicity in the mouse is not 

required under the 1884 Subdivision F 

guideline requirements.)

0, 50, 375, 1500, 7500 ppm

0, 7.5, 56.25, 225, 1125 mg/kg bw/day

Acceptable-Nonguideline 

NOAEL = M: 56.25 ; F: >1125 mg/kg 

bw/day

LOAEL = M: 225 mg/kg bw/day based 

on increased RBC and hemoglobin and 

decreased body weight gain and food 

efficiency. F: LOAEL not established.

870.3150

90-Day oral toxicity 

(dog)

41356322 (1989)

0, 250, 5000, 20000 ppm

0, 6.25, 125, or 500 mg/kg bw/day. 

Acceptable-Guideline

NOAEL = 6.25 mg/kg bw/day

LOAEL = 125 mg/kg/day based on 

urinary volume and osmolarity
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Table B.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No./ Study 

Type

MRID No. (year)/ Classification /Doses Results

870.3700a

Prenatal 

developmental in 

(Rat)

41356324 (1989)

0, 200, 700, 2000, 6000 mg/kg bw/day 

Acceptable-Guideline 

Maternal NOAEL ≥ 6000 mg/kg bw/day

LOAEL = not established

Developmental NOAEL ≥ 6000 mg/kg 

bw/day

LOAEL = not established

870.3700b

Prenatal 

developmental in 

(rabbit)

41356325 (1989)

0, 25, 170, 500, 1500 mg/kg bw/day

Acceptable-Guideline 

Maternal NOAEL = 170 mg/kg bw/day

LOAEL = 500 mg/kg bw/day based on 

death and reduced weight gain.

Developmental NOAEL = 500 mg/kg 

bw/day

Developmental LOAEL = 1500 mg/kg 

bw/day based on production of only two 

viable fetuses.

870.3800

Reproduction and 

fertility effects

(rat)

41931644 (1990)

0, 50, 3000, 15000 ppm 

0, 2.76, 165, 830 mg/kg bw/day (F0 males)

0, 3.38, 204, 1021 mg/kg bw/day (F0

females)

0, 3.66, 217, 1316 mg/kg bw/day (F1 males) 

0, 4.29, 264, 1316 mg/kg bw/day (F1

females)

Acceptable-Guideline 

Parental/Systemic NOAEL = 165 mg/kg 

bw/day in males, 204 mg/kg bw/day in 

females

Parental/Systemic LOAEL = M: 830; F: 

1021mg/kg bw/day based on decreased 

body weight gain in males and females

Reproductive NOAEL =1316 mg/kg 

bw/day (HDT)

Reproductive LOAEL = Not Established.

Offspring NOAEL = M: 217; F; 264 

mg/kg bw/day

LOAEL = 1316 mg/kg bw/day based on 

decreased mean body weight in F1 males, 

decreased body weight gain in F1 females 

and decreased daily food consumption in 

F1 males.
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Table B.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No./ Study 

Type

MRID No. (year)/ Classification /Doses Results

870.4100b

Chronic toxicity (dog)

41931643(1991)

0, 50, 2500, 10,000 ppm

0, 1.6, 81.8, 342.4 mg/kg bw/day (males); 

0,1.6, 86.5, 358.5 mg/kg bw/day (females) 

Acceptable-Guideline

Following re-evaluation (HED DOC. NO. 

012501, HIARC, 19/FEB/1998):

NOAEL = in males 81.8 mg/kg/day and 

in females 86.5 mg/kg bw/day.

LOAEL = 342.4 mg/kg/day) based on 

increased absolute liver and kidney 

weights and increased incidence of 

seminiferous tubule degeneration and 

increased numbers of spermatid giant 

cells present in epididymides in males. 

The LOAEL in females is 358.5 

mg/kg/day based on decreased mean body 

weight and body weight gain, increased 

serum cholesterol levels and alkaline 

phosphatase activity, increased absolute 

liver weight, and increased relative liver 

and kidney weights.

870.4200

Carcinogenicity

(rat)

42047701(1991)

0, 25, 300, 3000, 10,000 ppm

0, 1.0, 11.8, 121, 414 mg/kg bw/day 

(males)

1.38, 17.1, 163, 568 mg/kg bw/day (females)

Acceptable-Guideline

NOAEL = 11.8 mg/kg bw/day for males 

and 163 mg/kg/day for females.

LOAEL = 121 mg/kg bw/day for males 

and 568 mg/kg bw/day for females, based 

on decreased body weight gain and liver 

effects.

No evidence of carcinogenicity.

870.4300

Carcinogenicity

(mouse)

41931642 (1991)

0, 25, 250, 2500, or 7500 ppm 

0, 3.47, 35.5, 351, or 1127 mg/kg bw/day

(males) 

0, 4.99, 50.5, 488, or 1505 mg/kg bw/day

(females)

Acceptable-Guideline

NOAEL = 351 mg/kg bw/day (males); 

488 mg/kg bw/day (females).

LOAEL = 1127 mg/kg bw/day for males; 

and 1505 mg/kg bw/day, females, based 

on decreased mean body weight in males 

and females, increased incidence of 

dilation and cysts in the glandular 

stomach and degeneration of the testicular 

artery and tunica albuginea in males. 

No evidence of carcinogenicity.
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Table B.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No./ Study 

Type

MRID No. (year)/ Classification /Doses Results

870.5100

In vitro Bacterial 

Gene Mutation Assay

42471310 (1992)

Trial 1

5000, 1000, 750, 500, 100, 75, 50, 25, 10, 0 

μg/plate 

Trial 2 

5000, 2500, 1000, 750, 500, 100, 0 μg/plate 

in the presence and absence of mammalian 

metabolic activation with 0.5 ml S-9 mix.

Acceptable-Guideline

There was no evidence of induced mutant 

colonies over background.

870.5300

In Vitro Mammalian 

Cells in Culture Gene 

Mutation assay in 

CHO

41356328 (1989)

0, 10, 100, 250, 750, 1300 μg/mL in the 

presence and absence of mammalian 

metabolic activation with S/9.

Acceptable-Guideline

41356327 (1989)

0, 0.0008, 0.004, 0.008, 0.04, 0.08, 0.4, 0.8, 

or 1.1 mg/mL

Acceptable-Guideline

There was no evidence of induced mutant 

colonies over background.

There was no evidence that unscheduled 

DNA synthesis, as determined by 

radioactive tracer procedures [nuclear 

silver grain counts] was induced.
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Table B.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No./ Study 

Type

MRID No. (year)/ Classification /Doses Results

870.6200a

Acute Neurotoxicity 

(rat)

48710302 (2011)

0, 200, 1000, 2000 mg/kg

Acceptable- Guideline

NOAEL = 2000 mg/kg

LOAEL > 2000 mg/kg.

No clinical signs, changes in body weight 

and/or food consumption, gross or 

microscopic pathology, or 

neurobehavioral effects were observed

870.6200b

Subchronic 

Neurotoxicity (rat)

48710303 (2011)

0, 1000. 3000, 7500 ppm (M/F)

0, 55. 170, 438 mg/kg/day (M)

0, 69, 193, 507 mg/kg/day (F)

Acceptable- Guideline

NOAEL = 438/507 mg/kg/day (M/F)

LOAEL > 438/507 mg/kg/day (M/F)

No clinical signs, gross or microscopic 

pathology, or changes in survival, body 

weight and/or food consumption, 

fore/hind-limb grip strength, footsplay, 

body temperature, rearing, FOB 

measurements or motor activity were 

observed.

870.7800

28-day Immunotoxicity (mouse)

48710305 (2011)

0, 300, 600, 1800, 6500 ppm

0, 45, 93, 288, 1006 mg/kg/day

Acceptable- Guideline

NOAEL = 1006 mg/kg/day

LOAEL > 1006 mg/kg/day

No clinical signs, gross or microscopic 

pathology, or changes in body weight 

and/or food consumption, brain, spleen or 

thymus weights, or in humoral immune 

response were observed.
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Table B.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No./ Study 

Type

MRID No. (year)/ Classification /Doses Results

870-7485

Metabolism -- Rat

42540701 (1989)

Low Dose Group: C14-pyridine DPX-E9636 

administered once by oral gavage at a dose 

of 25 mg/kg (4.6 μCi/mg).

High Dose Group: Either C14-pyridineDPX-E9636 (0.47 μCi/mg) or C14

-

pyrimidine-DPX-E9636 (0.45 μCi/mg) was 

administered once by oral gavage at a dose 

of 250 mg/kg.

Repeat Dose: Either Propylene glycol, or 

unlabeled test compound, was administered 

by oral gavage for 14 consecutive days. On 

the 15th day treated animals received a single 

dose of C14-pyridine-DPX-E9636 (25 mg/kg, 

0.47 μCi/mg).

Acceptable/Guideline

There were no remarkable differences in 

the excretion pattern of either males or 

females in the low, high or repeat dose 

groups. Within the first 72 hours, greater 

than 90% of the administered 

radioactivity was excreted. Urinary 

elimination predominated, accounting for 

approximately 64% of the dose; 

approximately 30% was eliminated in the 

feces. Monitoring of the expired air 

indicated that less than 0.08% of the 

radiolabel was present in expired CO2. 

For all of the treatment groups, 93 to 96% 

of the radioactivity administered was 

recovered in either the feces (20 to 33%) 

or urine (58 to 67%). After 72 hours, the 

animals were sacrificed and the tissue 

distribution of labeled residues was 

determined. Low, but detectable amounts 

of radioactivity were found in the heart, 

lung, liver, kidney, and muscle; animals 

in the repeat dose groups also showed 

some accumulation in the spleen. Hepatic 

accumulation, although low, was slightly 

higher than other organs; within each 

treatment group, the males showed more 

accumulation in the liver than the 

females.

The metabolic profiles were determined 

on pooled urinary and fecal samples. The 

highest percentage of the urinary (42 to 

55%) and fecal (5 to 16%) radioactivity 

was attributed to unmetabolized parent 

compound. Metabolism largely involved 

either the contraction or cleavage of the 

sulfonylurea bridge. Following 

contraction of the sulfonylurea bridge, 

demethylation to metabolite P5 and 

subsequent hydroxylation to metabolite 

P4 occurred. Data on enzymatic (βglucuronidase) or acid hydrolysis were 

not presented. Therefore, the contribution 

of Phase II biotransformation reactions to 

the detoxification of DPX-E9636 could 

not be assessed.
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B.3 Executive Summaries

The executive summaries of the neurotoxicity and immunotoxicity studies represent new data 

and are presented below; the executive summaries of the other studies used in this risk 

assessment and/or appearing in Table A.2.2 are presented in a previous Risk Assessment 

document. Please refer to D. Rate, D333256, 05/16/2007.

870.6200 Acute and Subchronic Neurotoxicity Battery (rat) 

870.6200a

In an acute neurotoxicity study (MRID 48710302), rimsulfuron (99.8% a.i., Lot/Batch No. 

FEB10MA206) was administered to 12 male and 12 female Crl:CD(SD) rats/dose by gavage 

(single dose) at dose levels of 0, 200, 1000, or 2000 mg/kg on Study Day One and observed for 

14 days. The test vehicle was 5% (w/v) carboxymethylcellulose.

Endpoints evaluated included viability, body weights and body weight gains, food consumption, 

and clinical observations. Neurobehavioral assessment (functional observational battery and 

motor activity testing) was performed in 12 rats/sex/group pre-test, on the day of dosing, and on 

days 7 and 14 post dose. At study termination (day 16), 6 rats/sex/group were euthanized and 

perfused in situ for neuropathological examination. The control and 300 mg/kg rats were 

subjected to histopathological evaluation of brain and peripheral nervous system tissues. 

All rats survived to study termination. There were no clinical signs, and body weight and food 

consumption were comparable among the groups throughout the study in both sexes. No 

significant adverse effects on neurologic tissue or function were observed. Functional 

observation battery, motor activity, gross and microscopic pathology, all failed to show an 

increased incidence of adverse effects that could be related to treatment. Brain weight data were 

not reported for the study; however, in the absence of any functional or microscopic findings, 

this deficiency is not considered to significantly degrade the study.

The neurotoxicity LOAEL was not established. The NOAEL was 2000 mg/kg, the highest dose 

level in the study, and the limit dose.

870.6200b

In a subchronic neurotoxicity study, (MRID 48710303) Rimsulfuron (99.8% a.i., Lot/Batch No. 

FEB10MA206) was administered to 12 male and 12 female Crl:CD(SD) rats/dose in the diet at 

dose levels of 0, 1000, 3000, and 7500 ppm (Males: 0, 55, 170, 438 mg/kg/day, Females: 0, 69, 

193, 507 mg/kg/day) for approximately 90 days. Neurobehavioral assessments (functional 

observational battery and motor activity evaluation) were performed in12 rats/sex/group once 

pre-test and at weeks 4, 8, and 13. At study termination (test day 98 or 99), 6 rats/sex/group were 

euthanized and perfused in situ for neuropathological evaluation. Of the perfused animals. the 

control and 7500 ppm groups were subjected to a histopathological evaluation of brain and 

peripheral nervous system tissues. The remaining 6 rats/sex/group were sacrificed and discarded 

without necropsy on test day 100. 
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There were no treatment related effects on mortality, clinical signs, body weight, brain weight or 

gross and histologic pathology or neuropathology. Functional operational battery (FOB) and 

motor activity testing revealed no treatment-related effects.

The LOAEL was not established. The NOAEL was 7500 ppm, equivalent to 438 and 507 

mg/kg/day in males and females, respectively.

CLASSIFICATION: This study is classified as Acceptable /Guideline and satisfies the guideline 

requirements for a Subchronic Neurotoxicity study in rats, OPPTS 870.6200b. Although the 

dose levels could have been higher (no effects were observed), rimsulfuron is a sulfonylurea 

compound, and there is no indication of neurotoxicity in this class of compounds. Another study 

would not provide any useful data for risk assessment.

870.7800 Subchronic Immunotoxicity study (mouse) 

In an immunotoxicity study (MRID 48710305), Rimsulfuron (DPX-E9636) Technical (99.8% 

a.i., Lot# DPX-E9636-170) was administered to male Crl:CD-1(ICR) mice (10/dose) in the diet 

at dose levels of 0, 300, 600,1800, or 6500 ppm (equivalent to 0, 45, 93, 288, or 1006 mg/kg 

bw/day, respectively) for 28 consecutive days. Body weights, food consumption, and clinical 

observations were recorded during the in-life period. On test day 23, animals were injected 

intravenously in the lateral tail vein with 0.2 mL of sheep red blood cells (SRBC, 5 x 108/mL). 

The positive control animals were injected intraperitoneally with cyclophosphamide 

monohydrate (25 mg/kg/day) for 5 consecutive days (days 23-28). Five days after SRBC 

injection (test day 28), the animals were euthanized by isoflurane anesthesia and 

exsanguinations. Blood was collected from each mouse, from the abdominal vena cava while the 

animal was under isoflurane anesthesia, processed to serum, and frozen at <-60°C until analyzed. 

Humoral immune function was evaluated by analyzing sera from individual control and testsubstance treated animals for anti-SRBC IgM levels with an enzyme-linked immunosorbent 

assay (ELISA). At sacrifice, each animal was examined grossly and selected organs were 

weighed (brain, spleen, and thymus).

There were no adverse effects on clinical signs, body weight or nutritional parameters in any of 

the treated group compared with the control. 

The systemic toxicity NOAEL for Rimsulfuron in mice is 6500 ppm (equivalent 1006 mg/kg 

bw/day), tested above the limit dose. 

For immunotoxicity, there were no treatment-related effects on serum anti-SRBC IgM antibody 

levels as measured by an ELISA. A high inter-individual variability of anti-SRBC IgM level was 

noted in all the treatment groups as well as in the control group. Evaluation of individual animal 

data did not show any trend or distribution that would demonstrate significant suppression of the 

anti-SRBC antibody response. Animals in the positive control group showed marked decreases 

in the anti-SRBC IgM response. The positive control group confirmed the validity of the 

immunotoxicity assay. 
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The Natural Killer (NK) cells activity was not evaluated in this study. The toxicology database 

for Rimsulfuron does not reveal any evidence of treatment-related effects on the immune system. 

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

system. Under HED guidance, a NK cells activity assay is not required at this time. 

Under the conditions of this study, the NOAEL for immunotoxicity is 6500 ppm (equivalent to 

1006 mg/kg/day). The LOAEL was not established, tested above the limit dose.

This study is classified as acceptable/guideline and satisfies the guideline requirement for an 

immunotoxicity study (OPPTS 870.7800) in the mouse. 
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Appendix C: Chemical Name and Structures of Rimsulfuron and Metabolites

Company code; Chemical name Chemical structure

IN—70941

N-(4 ,6-Dimethoxy-2-pyrimidinyl)-N-((3-ethylsulfonyl)-2-pyridinyl) 

urea

IN-70942

N-((3-ethylsulfonyl)-2-pyridinyl)-4,6-dimethoxy-2-pyrimidinamine

IN-E9260

3-(Ethylsulfonyl )-2-pyridinesulfonamide.

IN-T5831

N-(4,6-dimethoxy-2-pyrimidinyl)urea

IN-69190

2-amino-4,6-dimethoxy-5-pyrimidinol

IN-J290

2-Amino-4,6-dimethoxypyrimidine
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Company code; Chemical name Chemical structure

IN-H1043

2-Amino-4,6-dihydroxypyrimidine

IN-JF999

N-[((3-Ethylsulfonyl)-2-pyridinyl)]-4-hydroxy-6-methoxy-2-

pyrimidineamine