Page 2 of 18

Executive Summary

The HED Registration Review Team has evaluated the most recent human health assessments 

and database for the herbicide rimsulfuron to determine whether sufficient data are available and 

whether any updates are needed to support Registration Review. HED has considered the most 

recent human-health risk assessments for rimsulfuron, updates to the toxicity, exposure, and 

usage databases, and current Agency science policy and risk assessment methodologies to 

determine the scope of work necessary to support Registration Review. In addition, HED 

conducted an open literature search to look for new literature relevant to the human health risk 

assessment. The results of the literature search showed that no new information relevant to the 

human health risk assessment has been published.

Rimsulfuron is a sulfonylurea herbicide (Group 2) used to control certain broad-leaf weeds and 

grasses, and acts by inhibiting the acetolactate synthase (ALS) biochemical process, a process 

not present in humans. Rimsulfuron has low acute toxicity but is a moderate eye irritant. With 

repeated dosing, the kidney and liver were the primary target organs of rimsulfuron toxicity. 

Subchronic studies indicate 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. Rimsulfuron is classified as “Not Likely to be Carcinogenic to Humans.” It 

is negative for mutagenicity in a battery of genotoxicity studies. The toxicity and exposure

database supported the reduction of the FQPA Safety Factor to 1X. 

Sufficient data are available to assess the toxicity of rimsulfuron. All the requirements of the 

new Part 158 guidelines have now been submitted or waived. The recently submitted 

immunotoxicity, acute neurotoxicity and subchronic neurotoxicity studies are currently under 

review. Once these new studies have been completely reviewed, the rimsulfuron Registration 

Review Team recommends that the points of departure and safety factors used for risk 

assessment purposes for rimsulfuron be re-examined. 

Rimsulfuron is currently registered for use on non-residential turf such as golf courses, sod farms

athletic fields, industrial and commercial lawns and similar nonresidential areas. Additionally, it 

is registered on agricultural food crops including bushberries, caneberries, soybeans, potatoes, 

field corn, tomatoes, grapes, various tree fruits, and tree nuts. There is currently a pending use 

on chicory.

The residue chemistry database is sufficient to support current and pending registrations of 

rimsulfuron. The nature of the residue in plants and livestock has been defined. Adequate field 

trial, rotational crop, and storage stability data are available. 

A new risk assessment may be needed depending on the results of the toxicology studies that are 

currently in review and the reevaluation of databases using current policies. Occupational 

exposure assessments may need to be reassessed based on current Occupational and Residential 

Exposure (ORE) policies and exposure data and to consider the exposures that were not 

previously assessed due to the lack of the endpoints at the time the risk assessment was being 
Page 3 of 18

conducted. In addition, the Agency may need to consider off-target movement of pesticides into 

residential settings.

Introduction

HED has evaluated the existing human health risk assessments for rimsulfuron to determine 

whether sufficient data are available and whether a new human health risk assessment is needed 

to support Registration Review. HED has considered the most recent risk assessments for 

rimsulfuron, updates to its toxicity, exposure and usage databases, and current Agency science 

policies and risk assessment methods. The most recent risk assessment for rimsulfuron was 

conducted in 2012 (D391083, C. Walls, 5/04/12). 

Hazard Identification/Toxicology

Rimsulfuron belongs to the pyrimidinylsulfonylurea class of herbicides and controls weeds by 

inhibiting the acetolactate synthase (ALS) biochemical process. Since ALS is a component in 

the synthesis of some essential amino acids, weed survival and growth are inhibited. A direct 

correlation of this mode of action in plants to a mode of action in mammals is not clear because 

ALS is not present in mammals.

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. 

Effects seen in the subchronic and/or chronic toxicity studies in one or more species included 

decreased body weight and body weight gain, increased relative and/or absolute liver and kidney 

weights, diuresis (increased urine volume), decreased liver enzymes and bilirubin and increased 

serum cholesterol, fatty change, hepatocellular hypertrophy, increased red blood cell (RBC), 

hemoglobin and platelet concentration, increased incidences of dilation and cysts in the glandular 

stomach, degeneration of the testicular artery and tunica albuginea, increased incidence of 

seminiferous tubule degeneration and increased numbers of spermatid giant cells present in 

epididymides in males.

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 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/offspring toxicity was seen in the presence of maternal/systemic toxicity of 

comparable severity, and at similar dose levels. Consequently, there is no quantitative or 

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

there are no concerns or residual uncertainties. There was no evidence of neurotoxicity or 

immunotoxicity in the recently submitted studies which have undergone preliminary evaluation 
Page 4 of 18

and are currently under detailed review. Therefore, HED has concluded that the FQPA Safety 

Factor should be reduced to 1X.

All the requirements of the revised 40 CFR Part 158 guidelines have now been submitted or 

waived. The recently submitted immunotoxicity, acute neurotoxicity and subchronic 

neurotoxicity studies are currently under review. Once these new studies have been completely

reviewed, the rimsulfuron Registration Review Team recommends that the points of departure 

and safety factors used for risk assessment purposes for rimsulfuron be re-examined. 

Toxicity endpoints, points of departure, and safety factors for rimsulfuron risk assessment were 

initially selected by HED in 1998 (HED Document No. 012501, J Rowland, 19/FEB/1998) and 

updated in 2006 (TXR # 0054356, E. Rinde, 27/SEP/2006) and in 2011 (D384623, E. Holman, 

11/04/11) for the following exposure scenarios: chronic dietary; short- and intermediate-term 

dermal, and short- and intermediate-term inhalation. Long-term dermal and inhalation endpoints 

were not identified because exposure is not anticipated for these scenarios. An endpoint for 

acute dietary risk was not selected because no adverse effects were observed which could be 

attributed to a single dose exposure. 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.

The toxicity endpoints are presented in Attachment 3.

Conclusions: No new toxicity data are required to support the registration review of rimsulfuron. 

Once all data have been reviewed, the rimsulfuron Registration Review Team recommends that 

the points of departure and safety factors used for risk assessment purposes for rimsulfuron be 

re-examined. However, a preliminary screen of the recently submitted studies indicate that the 

PODs will not change.

Dietary Exposure

The residue chemistry data and drinking water data are adequate to assess dietary exposure. The 

most recent dietary (food and drinking water) exposure assessment was conducted in 2011

(D394389, E. Holman, 10/28/11) using the Dietary Exposure Evaluation Model DEEM-FCIDTM, 

Version 2.03. This assessment was conducted to support the pending 2012 PRIA action for an 

additional food use on chicory. The dietary exposure assessment relies on conservative inputs 

(tolerance level residues, 100% crop treated, DEEMTM default processing factors) to model 

exposure to rimsulfuron through food and drinking water. 

The estimated drinking water concentration (EDWC) of rimsulfuron was provided by the 

Environmental Fate and Effects Division (EFED) and incorporated directly into the chronic 

assessment. EFED estimated residues of rimsulfuron in surface water and groundwater using the 

FIRST and SCIGROW (Screening Concentrations in Groundwater) models, respectively. The 

chronic surface water EDWC (0.120 ppb) was higher than the groundwater EDWC (0.016 ppb); 

therefore, the surface water value of 0.120 ppb was used in the chronic dietary assessment. The 

assessments are based on reliable data and will not underestimate exposure/risk.
Page 5 of 18

The chronic dietary exposure estimates for food and drinking water are below HED’s level of 

concern for the general U.S. population and all population subgroups (<1% of the cPAD for the 

general U.S. population and <1% of the cPAD for children 1 to 2 years old, the most highly 

exposed population subgroup). 

HED classified rimsulfuron as “no evidence of carcinogenicity to humans;” therefore, 

quantification of human cancer risk was not conducted. 

The residue chemistry database is sufficient to support current and pending registrations. The 

nature of the residue in plants and livestock has been defined. The residue of concern in plant 

and livestock commodities for risk assessment and tolerance setting purposes is rimsulfuron. No 

tolerances have been established for livestock commodities. Acceptable high performance liquid 

chromatography with tandem mass spectroscopy detection (LC/MS/MS) and HPLC/UV (ultraviolet) methods are available to enforce the established tolerances. Rimsulfuron is not recovered 

by FDA Multiresidue Methods.

Adequate storage stability data are available to support storage durations for rimsulfuron. 

Adequate confined rotational crop data are available to support minimum plant-back intervals up 

to 18 months, depending on the end-use product. 

Conclusions: Provided that EFED drinking water estimates do not need revision, a new dietary 

assessment for rimsulfuron may not be required for the purpose of registration review. 

Furthermore, although a new version of DEEM (Version 3.04) will be released, a new dietary 

risk assessment may not be needed since it is anticipated that the changes in the model will not 

affect the risk conclusion.

Residential Exposure

Residential Handlers

A residential handler exposure assessment is not required because rimsulfuron is only applied to 

use sites that are not treated by residential handlers (e.g., golf courses and other non-residential 

turf areas such as industrial parks, tank farms, sod farms, seed farms, and professionally 

managed sports fields).

Residential Post-Application 

Based on the current use patterns, there is only potential for post-application dermal exposure for 

recreational golfers. Dermal exposure was not assessed at the time of registration because no

dermal endpoint was selected based on the lack of dermal toxicity. However, the endpoints have 

been re-evaluated since the golf course turf registration and a dermal endpoint has now been 

selected. Therefore, a new risk assessment is needed for the existing golf course turf use. 
Page 6 of 18

Conclusions: A new risk assessment is needed include the short-term dermal exposure for the 

recreational golfer.

Aggregate Risk Assessment

Aggregate assessments consider exposures from food, drinking water, and residential uses. In 

the most recent human health risk assessment (D391083, C. Walls, 5/04/12), aggregate risks 

were estimated for the chronic (food and drinking water) exposure duration. As previously 

mentioned, these aggregate dietary risks were below HED’s level of concern. As previously 

stated, a dermal end point was not selected when the golf turf was first registered. However, the 

endpoints have been re-evaluated since the golf turf registration and a dermal endpoint has now 

been selected. Therefore, short-term aggregate risk assessments are now required since a short 

or intermediate-term dermal toxicity endpoint has been identified. 

Conclusions: Currently, the aggregate risk assessment includes only food and drinking water. 

However, it will need to be reassessed to include the short-term dermal exposure for the 

recreational golfer.

Occupational Exposure

Rimsulfuron is currently registered for use on several agricultural crops as well as on golf course 

and other professionally managed turf areas. There is potential for short- and intermediate-term 

occupational exposure to rimsulfuron during handling (mixing, loading, and applying) and postapplication activities.

Occupational Handlers

Occupational handler exposure and risk assessments have been conducted on caneberries, 

bushberries, and the pending use on chicory. The resulting risk estimates are not of concern 

(MOEs ranging from 370 to 11,000). Occupational exposure and risk assessments were not 

conducted for uses on golf course, sod farms athletic fields, industrial and commercial lawns and 

similar nonresidential areas or the agricultural food crops including soybeans, potatoes, field 

corn, tomatoes, grapes, various tree fruits, and tree nuts. Dermal and inhalation end points were 

not selected due to lack of observed toxic effects when these uses were registered. However, the 

endpoints have been re-evaluated and dermal and inhalation endpoints have now been selected. 

Therefore, a new occupational handler risk assessment is needed.

Occupational Post-Application

There is a possibility for agricultural workers to have post-application dermal exposure to 

rimsulfuron following its uses. Based on the use pattern for bushberries and caneberries, it was 

determined that post-application dermal exposure would be negligible and therefore not 

quantitatively assessed. Additionally, the resulting post-application risk estimates for chicory are 

also not of concern (MOEs ranging from 1,300 to 12,000). 
Page 7 of 18

Occupational post-application exposure and risk assessments were not conducted for the 

following uses: soybeans, potatoes, field corn, tomatoes, grapes, various tree fruits, tree nuts, and 

golf course turf because when these uses were registered a dermal end point was not selected due 

to lack of observed toxic effects. However, the endpoints have been re-evaluated and a dermal 

endpoint has now been selected. Therefore, a new occupational post-application risk assessment 

is needed. 

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

exposure assessment has not been performed for rimsulfuron at this time. However, there are 

multiple potential sources of post-application inhalation exposure to individuals performing postapplication activities in previously treated fields. These potential sources include volatilization 

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

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

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

The Agency received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report as well as available post-application inhalation exposure 

data generated by the Agricultural Reentry Task Force and 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.

Conclusions: There is sufficient information available to assess occupational handler and postapplication exposures. However, not all of the occupational exposure scenarios were assessed 

based on current ORE policies and current toxicological endpoints. An up-to-date handler and 

post-application occupational assessment is needed, accounting for the changes in policies and 

endpoints. 

Public Health and Pesticide Epidemiology Data

The evaluation of the OPP Incident Data System (IDS) indicated nine incidents identified in the 

United States for rimsulfuron in either Main or Aggregate IDS, from January 1, 2007 to February 

22, 2012 (D402251, S. Recore, 05/08/12). Based on the low frequency and severity of incident 

cases, there does not appear to be a concern at this time that would warrant further investigation. 

The Agency will continue to monitor the incident information and if a concern is triggered, 

additional analysis will be included in the risk assessment.

 

Tolerance Assessment and International Harmonization

The US tolerances for field corn grain, potatoes, and tomatoes are harmonized with Canada. The 

US tolerance for bushberry subgroup 13-07B is not in harmony with Canada; the US tolerance of 

0.01 ppm is established based on field trial data on blueberries. The Canadian MRL was not 

established for subgroup 13-07B but was established at 0.05 ppm on blueberries. There are no 

Codex MRLs established for rimsulfuron (See Attachment 2).
Page 8 of 18

Environmental Justice

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

human health risk assessment, in accordance with US 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 

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.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of the most recent registration decision, EPA reviewed these data and 

selected the most sensitive endpoints for the relevant risk assessment scenarios from the existing 

hazard database. However, as required by FFDCA section 408(p), flazasulfuron is subject to the 

endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the 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 
Page 9 of 18

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 dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. 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. Rimsulfuron is 

not among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for rimsulfuron. For further information 

on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the 

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

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

Cumulative 

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

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

to 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 not 

assumed that rimsulfuron has a common mechanism of toxicity with other substances. For 

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

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

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

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

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

Human Studies

The previous risk assessments rely 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, 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.

Data Requirements/ Outstanding Deficiencies

None

References

As shown in References below, only four human health risk assessments have been conducted 

for rimsulfuron. 
Page 10 of 18

Memoranda Relevant to Registration Review of Rimsulfuron

Author Barcode 

(DP#)

Date Title

S. Recore 402251 05/08/12 Rimsulfuron: Review of Human Incidents

C. Walls 391083 05/04/12 Rimsulfuron. Human Health Risk Assessment for Proposed 

Section 3 Use on Chicory

M. Barrett 391086 3/15/12 Tier I Estimated Drinking Water Concentrations of 

Rimsulfuron, for the Use in the Human Health Risk 

Assessment: New Use Request for the Use of Rimsulfuron on 

“Chryosolite” Variety of Sulfonylurea Tolerant Chicory

E. Holman 384623 11/04/11 Rimsulfuron. Human Health Risk Assessment for Proposed 

Section 3 Uses on Caneberry and Bushberry. 

E. Holman 394389 10/28/11 Rimsulfuron: Chronic Aggregate Dietary (Food and Drinking 

Water) Exposure and Risk Assessment for the Section 3 

Registration on Caneberry, Bushberry, and Chicory

D. Rate 358866 09/08/09 Rimsulfuron. Human Health Risk Assessment for Proposed 

Section 3 Uses on Genetically Modified Field Corn and 

Soybean

D. Rate 333256 05/16/07 Rimsulfuron: Human Health Risk Assessment for Proposed 

Uses on Almonds; Citrus Fruit; Grapes; Pistachio; Pome 

Fruit; Stone Fruit; and Tree Nuts.

E. Rinde 09/27/06 Rimsulfuron - Updated Executive Summaries and Section 4.0 

of Risk Assessment Document for Registration Action 

Branch 2

J Rowland 02/19/98 RIMSULFURON: - Report of the Hazard Identification 

Assessment Review Committee.

Attachments

1. Chemical Identity Table

2. International Residue Limits

3. Endpoint Selection Table and Toxicity Profiles
Page 11 of 18

Attachment 1

Chemical Identity Table

Table 1.1. Chemical Identity of Rimsulfuron

Chemical Structure

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

PC Code 129009

Chemical Class Sulfonylurea herbicide

Table 1.2. Chemical Names and Structures for Rimsulfuron Metabolites/Degradates

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.

N S

O

N

O H

N

H

O N

N OCH3

OCH3

SO2C2H5
Page 12 of 18

Table 1.2. Chemical Names and Structures for Rimsulfuron Metabolites/Degradates

Company code; Chemical name Chemical structure

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

IN-H1043

2-Amino-4,6-dihydroxypyrimidine

IN-JF999

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

pyrimidineamine
Page 13 of 18

Attachment 2

International Residue Limits

Rimsulfuron (PC Code-129009; 03/21/2012)

Table 2. Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180. 478 :

(a) General: rimsulfuron, N-((4,6-

dimethoxypyrimidin-2-

yl)aminocarbonyl)-3-(ethylsulfonyl)-2-

pyridinesulfonamide)

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

pyrimidinyl)amino]carbonyl]-

3-

(ethylsulfonyl)-2-

pyridinesulfonamide

None

Commodity

Tolerance (ppm) /Maximum Residue Limit 

(mg/kg)

US Canada Mexico1 Codex

Almond, hulls 0.09

Bushberry, subgroup 13–07B 0.01 0.05 blueberries

Caneberry, subgroup 13–07A 0.01

Corn, field, forage 0.4

Corn, field, grain 0.1 0.1 field corn

Corn, field, stover 2.5

Fruit, citrus, group 10 0.01

Fruit, pome, group 11 0.01

Fruit, stone, group 12 0.01

Grain, aspirated fractions 4.5

Grape 0.01

Nut, tree, group 14 0.01

Pistachio 0.01

Potato 0.1 0.1 potatoes

Soybean, forage 0.25

Soybean, hay 1.2

Soybean, hulls 0.04

Soybean, seed 0.01

Tomato 0.05 0.05 tomatoes

Completed: M. Negussie; 03/21/2012

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
Page 14 of 18

Attachment 3

Summary of Rimsulfuron Endpoints Selected for Risk Assessment

Table 3.1. 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/FQPA 

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

Short-Term 

(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.

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. 
Page 15 of 18

Toxicity Profiles

Table 3.2 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, 

41931624,41

931635

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

Table 3.3 Subchronic, Chronic and Other Toxicity Profile - Rimsulfuron

Guideline No./ Study 

Type

MRID No. (year)/ Classification /Doses Results

870.3100

90-Day oral toxicity 

(rat)

41356321 (1989)/ ACCEPTABLEGUIDELINE 

0, 50, 1500, 7500, 2000 ppm (0, 2.5, 75, 

375, 1000 mg/kg bw/day)

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)/ ACCEPTABLENONGUIDELINE (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)

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)/ ACCEPTABLEGUIDELINE 

0, 250, 5000, 20000 ppm (0, 6.25, 125, or 

500 mg/kg bw/day). 

NOAEL = 6.25 mg/kg bw/day

LOAEL = 125 mg/kg/day based on 

urinary volume and osmolarity
Page 16 of 18

Table 3.3 Subchronic, Chronic and Other Toxicity Profile - Rimsulfuron

Guideline No./ Study 

Type

MRID No. (year)/ Classification /Doses Results

870.3700a

Prenatal 

developmental in 

(Rat)

41356324 (1989)/ ACCEPTABLEGUIDELINE 

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

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)/ ACCEPTABLEGUIDELINE 

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

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)/ ACCEPTABLEGUIDELINE 

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); and 0, 4.29, 264, 1316 mg/kg 

bw/day (F1 females) respectively).

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.

870.4100b

Chronic toxicity (dog)

41931643(1991)/ ACCEPTABLEGUIDELINE 

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) respectively)

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.
Page 17 of 18

Table 3.3 Subchronic, Chronic and Other Toxicity Profile - Rimsulfuron

Guideline No./ Study 

Type

MRID No. (year)/ Classification /Doses Results

870.4200

Carcinogenicity

(rat)

42047701(1991)/ ACCEPTABLEGUIDELINE 

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)]

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)/ ACCEPTABLEGUIDELINE 

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)]

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.

870.5100

In vitro Bacterial 

Gene Mutation Assay

42471310 (1992)/ ACCEPTABLEGUIDELINE 

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

μg/plate and (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.

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)/ ACCEPTABLEGUIDELINE 

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

presence and absence of mammalian 

metabolic activation with S/9.

41356327 (1989)/ ACCEPTABLEGUIDELINE 

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

or 1.1 mg/mL

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.
Page 18 of 18

Table 3.3 Subchronic, Chronic and Other Toxicity Profile - Rimsulfuron

Guideline No./ Study 

Type

MRID No. (year)/ Classification /Doses Results

870.6200a

Acute Neurotoxicity 

(rat)

48710302 (2011)

0, 200, 1000, 2000 mg/kg

NOT YET CLASSIFIED – study under 

review

Provisionary NOAEL = 2000 mg/kg

Provisionary 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)

NOT YET CLASSIFIED – study under 

review

Provisionary NOAEL = 438/507 

mg/kg/day (M/F)

Provisionary 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

NOT YET CLASSIFIED – study under 

review

Provisionary NOAEL = 1006 mg/kg/day

Provisionary 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.