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Table of Contents

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

2.0 Regulatory Conclusions and Recommendations............................................................ 6

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

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

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

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

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

2.3.1 Recommendations from Residue Reviews.......................................................... 8

2.3.2 Recommendations for Worker Safety................................................................. 8

2.3.3 Recommendations for Residential Safety ........................................................... 8

3.0 Ingredient Profile .............................................................................................................. 8

3.1 Structure and Nomenclature ............................................................................... 8

3.2 Physical and Chemical Properties....................................................................... 9

3.3 Summary of Existing/Proposed Uses .................................................................. 9

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

4.1 Toxicology Studies Available for Analysis........................................................ 10

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME).................... 10

4.2.1 Dermal Absorption ............................................................................................. 11

4.3 Toxicological Effects........................................................................................... 11

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

4.4.1 Completeness of the Toxicology Database........................................................ 12

4.4.2 Evidence of Neurotoxicity .................................................................................. 12

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

4.4.4 Residual Uncertainty in the Exposure Database.............................................. 12

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

4.5.1 Dose-Response Assessment ................................................................................ 13

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment14

4.5.3 Cancer Classification and Risk Assessment Recommendation ...................... 14

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

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

5.0 Dietary Exposure/Risk Characterization ..................................................................... 15

5.1 Pesticide Metabolism and Environmental Degradation.................................. 15

5.1.1 Metabolism in Primary Crops and Livestock ...................................... 15

5.1.2 Metabolism in Rotational Crops............................................................ 15

5.1.3 Analytical Methodology.......................................................................... 16

5.1.4 Magnitude of the Residue in Plants....................................................... 16

5.1.5 Environmental Degradation .................................................................. 17

5.1.6 Comparative Metabolic Profile ............................................................. 17

5.1.7 Residues of Concern Summary.............................................................. 17

5.1.8 Drinking Water Residue Profile ............................................................ 17

5.1.9 Food Residue Profile............................................................................... 18

5.2 Dietary Exposure and Risk ................................................................................ 19

5.2.1 Acute Dietary Exposure/Risk................................................................. 19

5.2.2 Chronic Dietary Exposure/Risk............................................................. 19
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5.2.3 Cancer Dietary Risk ............................................................................... 19

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

6.1.1 Spray Drift........................................................................................................... 20

7.0 Aggregate Risk Assessments and Risk Characterization............................................ 20

8.0 Cumulative Risk Characterization/Assessment........................................................... 20

9.0 Occupational Exposure/Risk Pathway.......................................................................... 21

9.1 Short-Term Handler Risk .................................................................................. 21

9.2 Post-application Exposure and Risk ................................................................. 24

9.3 Restricted Entry Interval (REI) ........................................................................ 25

10.0 Data Needs and Label Recommendations .................................................................... 25

10.1 Toxicology............................................................................................................ 25

10.2 Residue Chemistry .............................................................................................. 26

10.3 Occupational and Residential Exposure........................................................... 26

11.0 References:....................................................................................................................... 26

Appendix A: Physical and Chemical Properties...................................................................... 27

Appendix B: Toxicology Assessment........................................................................................ 28

B.1 Toxicity Profiles....................................................................................................... 28

Appendix C: Chemical Name and Structures of Rimsulfuron and Metabolites .................. 32

Appendix D: Review of Human Research ................................................................................ 34

Appendix E. International Residue Limit Status Sheet ......................................................... 35
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1.0 Executive Summary

Use Profile:

Rimsulfuron is a sulfonylurea herbicide (Group 2) 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, 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. Rimsulfuron is a low hazard, low exposure and low risk chemical. The previous risk 

assessment for rimsulfuron was conducted November 4, 2011 (D384623, E. Holman 11/4/11)

Interregional Research Project No. 4 (IR-4) has submitted a petition supporting the use of 

rimsulfuron on chicory (roots and tops) (PP# 1E7883). The proposed formulation is a water 

dispersible granule (WG/WDG) multiple active ingredient (MAI) product (Basis® Herbicide; 

EPA Reg. No. 352-571), containing 50% rimsulfuron and 25% thifensulfuron-methyl. Basis 

Herbicide® is to be applied only to “Chrysolite” variety of sulfonylurea tolerant chicory from 

Florimond Desperez seed company. This assessment addresses the potential exposure and risk

of rimsulfuron only.

Human Health Risk Assessment:

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

assessment purposes. All the requirements of the new Part 158 guidelines have now been 

submitted or waived. The recently submitted immunotoxicity, acute neurotoxicity and 

subchronic neurotoxicity studied are currently under review.

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.

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. 
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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/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 

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

Factor should be reduced to 1X.

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.

Dietary Exposure (food/drinking water):

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

The chronic dietary food exposure assessments are conservative. The assessments are based on 

reliable data and will not underestimate exposure/risk.

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

to a single dose has not been identified for rimsulfuron.

Chronic: HED conducted an unrefined chronic dietary assessment, based on the assumption that 

rimsulfuron residues are present at tolerance levels in all commodities for which tolerances have 

been established, and that 100% of those crops are treated. Risks from this chronic dietary 

exposure are <1 % of the cPAD, and are therefore below the level of concern for the general US 

population and all population subgroups.

Cancer: Rimsulfuron is classified as “not likely to be carcinogenic to humans”; therefore, there 

is no cancer risk associated with exposure to rimsulfuron.

Residential Exposure:

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

assessment was not conducted.

Aggregate Risk:

Acute: Acute exposures were not considered because an adverse effect attributable to a single 

dose was not identified. 
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Chronic: Aggregate chronic risk is equivalent to chronic dietary risk. There is potential chronic 

exposure via the diet (food and drinking water) and estimated chronic risk is <1% of the cPAD 

as determined in Section 5.4. 

Occupational Exposure/Risk:

Agricultural Handlers: Occupational short-term (1 - 30 days) and intermediate-term (1 - 6 

months) dermal and inhalation exposures are expected from rimsulfuron handler activities 

associated with the proposed agricultural use. 

HED used data from the Pesticide Handlers Exposure Database (PHED) Version 1.1 as presented 

“Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” 

(http://www.epa.gov/pesticides/science/handler-exposure-table.pdf), dated March 2012). The 

estimated short- and intermediate-term combined dermal and inhalation margins of exposure 

(MOEs) ranged from 8,800 to 11,000. HED's level of concern (LOC) is an MOE less than 100, 

and therefore the estimated risks for handlers applying rimsulfuron to chicory are not of concern. 

Agricultural Post-application: A post-application dermal exposure assessment was conducted

using surrogate data and default assumptions. The estimated short- and intermediate-term 

combined dermal and inhalation margins of exposure (MOEs) ranged from 1,300 to 12,000. 

HED's LOC is an MOE less than 100, and therefore the estimated risks for post-application 

activities in chicory fields are not of concern. 

Based on the Agency's current practices, a quantitative post-application inhalation exposure noncancer assessment was not performed for rimsulfuron at this time. 

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

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

Review of Human Research: This risk assessment relies in part on data from studies in which 

adult human subjects were intentionally exposed to a pesticide or other chemical. These studies 

(listed in Appendix D) have been determined to require a review of their ethical conduct, and one 

of these studies is also subject to review by the Human Studies Review Board. All of the listed 

studies have received the appropriate review.

2.0 Regulatory Conclusions and Recommendations

Provided that a revised Section B (OPPTS 860.1200) is submitted, HED can recommend for an

unconditional registration and permanent tolerances for the proposed uses of rimsulfuron on 

chicory tops and roots. No additional data are needed as conditions of registration as outlined in 

Section 2.1 below. The specific tolerance recommendations are discussed in Section 2.2, and 

label modifications are discussed in Section 2.3.

2.1 Data Deficiencies/Conditions of Registration
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The following must be provided prior to a tolerance being established or registration 

allowed:

860.1200 Directions for Use

The Section B and the supplemental label for use on chicory should be revised to specify 

a minimum preharvest interval (PHI) of 110 days, based on field trial data.

The following data are required as a condition of registration:

None

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Currently, a high performance liquid chromatography/ultraviolet detection (HPLC/UV) method 

exists for the enforcement of tolerances for residues of rimsulfuron in/on corn, potato, and 

tomato commodities. The method, AMR-1241-88, involves extraction of samples with pH 7 

potassium phosphate buffer and methanol (75:25, v:v). The extract is acidified to pH 2.5-3.5 

(using concentrated phosphoric acid) and filtered for analysis by HPLC/UV with column 

switching, using a phenyl column for clean-up chromatography followed by an Rx column for 

analytical chromatography. The limit of quantitation (LOQ) is 0.05 ppm.

DuPont also proposed two additional methods using liquid chromatography with tandem mass 

spectrometry (LC/MS/MS) for tolerance enforcement: Method DuPont-15033 for watery and dry 

crop matrices, and Method DuPont-15027 for oily crop matrices. These methods were also 

adequate for data collection, as shown in the submitted studies. The validated LOQ is 0.010 ppm 

in each matrix. 

2.2.2 International Harmonization

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

chicory. An International Residue Limit Status sheet is attached (Appendix E).

2.2.3 Recommended Tolerances

HED concurs with the proposed tolerances and recommends for the following residue definition:

Note to PM: The Tolerance Expressions for rimsulfuron should be revised as follows:

Tolerances are established for residues of the herbicide rimsulfuron, including its 

metabolites and degradates, in or on the commodities in the table below. Compliance 

with the tolerance levels specified below is to be determined by measuring only 
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rimsulfuron (N-[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]-3-(ethylsulfonyl)-2-

pyridinesulfonamide).

Chicory, tops.................................................................................0.01 ppm

Chicory, roots................................................................................0.01 ppm

2.2.4 Revisions to Petitioned-For Tolerances

None

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

The supplemental label for use on chicory should be revised to specify a minimum PHI of 110 

days, based on field trial data.

2.3.2 Recommendations for Worker Safety

The personal protective equipment (PPE) and Restricted Entry Interval (REI) recommended on 

the label are considered appropriate.

2.3.3 Recommendations for Residential Safety

There are no proposed residential uses for rimsulfuron, therefore there are no residential safety 

recommendations noted.

3.0 Ingredient Profile

Rimsulfuron is a sulfonylurea herbicide (Group 2) that works via inhibition of acetolactate 

synthase (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. 

3.1 Structure and Nomenclature

Table 3.1. Rimsulfuron Nomenclature.

Compound

N S

O

N

O H

N

H

O N

N OCH3

OCH3

SO2C2H5
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Table 3.1. Rimsulfuron Nomenclature.

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 and chemical properties of rimsulfuron are provided in Appendix A.

3.3 Summary of Existing/Proposed Uses

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

bushberries, caneberries, 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. 

DuPont’s BASIS® Herbicide (EPA Reg. No. 352-571) is a water dispersible granule formulation 

containing 50% active ingredient. It is applied as postemergence broadcast spray using ground 

equipment to chicory. A single broadcast spray application of rimsulfuron to chicory may be 

made at a maximum application rate of 0.009 lb ai/A (0.3 oz/A) or two sequential applications at 

0.0047 lb ai/A (0.15 oz/A) may be made. The total application rate cannot exceed 0.009 lb 

ai/A/growing season (0.3 oz/A/growing season). BASIS® can be applied only to “Chrysolite” 

variety of sulfonylurea tolerant chicory. Application of BASIS® prior to the 2-true leaf stage, or 

after the 4-true leaf stage of Chrysolite chicory could result in crop injury.

The proposed use pattern is summarized in Table 3.1.
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Table 3.1 Summary of Directions for Use of Rimsulfuron.

Applic. Timing, 

Type, and 

Equipment

Formulation

[EPA Reg. 

No.]

Applic. 

Rate 

lb ai/A

Max. No. 

Applic. 

per 

Season

RTI1

(days)

Max. 

Seasonal 

Applic. 

Rate 

lb ai/A

PHI

(days)

Use Directions and 

Limitations

Sulfonyl-Tolerant Varieties of Chicory “Chrysolite”

Postemergence, 

2-true leaf stage 

to 8-true leaf 

stage; Broadcast, 

foliar; Ground 

equipment only.

Basis 

Herbicide

50% WDG

[352-571]

0.009

(0.3

ounce/

A)

1

--

0.009

(0.3 

ounce/A)

90

Apply in 19-30 

gallons/acre (GPA). Can 

be used with both a 

nonionic surfactant at min 

of 0.25% v/v (1qt/100 gal 

spray solution) and an 

ammonium 

nitrogen/sulfate fertilizer 

(rate of 2 qt/A). 

0.005

(0.15

ounce/

A)

2

1 RTI = Retreatment interval

4.0 Hazard Characterization and Dose-Response Assessment

4.1 Toxicology Studies Available for Analysis

Studies available for hazard characterization include three 90-day oral toxicity feeding studies 

(rats, mice, dog); two prenatal developmental toxicity studies (rat, rabbit); a reproduction and 

fertility effects study in rats; a chronic dog feeding study; a metabolism study; genotoxicity 

studies; a combined chronic toxicity/carcinogenicity study in rats and a carcinogenicity study in 

mice. Additional studies, currently under HED review, include acute and subchronic 

neurotoxicity studies and an immunotoxicity study.

This toxicological database for rimsulfuron is adequate for risk assessment purposes. In 

accordance with the new Part 158 guidelines, a 21/28 day dermal toxicity study is required. 

However, this dermal toxicity study has been waived and is no longer required because, due to 

expected low toxicity by the dermal route and demonstrated low dermal exposure, dermal risks 

are below HED’s level of concern. Regarding the other required Part 158 studies currently under 

review, preliminary evaluation of the data show an absence of neurotoxicity and immunotoxicity 

at any of the dose levels, and these studies are not expected to change points of departure or 

endpoints selected in this risk assessment.

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

The metabolism of 14C-labeled rimsulfuron was studied in male and female rats. Single dose 

exposure rats were treated once by oral 14C -pyridine-labeled or 14C-pyrimidine-labeled 

compound. The repeat dose groups were gavaged orally with unlabeled test compound for 14 

consecutive days, followed on the 15th day by 14C -pyridine-test compound. Tissue distribution 

of labeled residues was low. Males showed slightly higher hepatic accumulation than females 

within each test group. Animals in the repeat dose groups also showed a slight accumulation in 
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the spleen. The metabolic profiles were determined using 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. The parent compound is metabolized by cleavage or 

contraction of the sulfonylurea bridge, leading to the formation of 3- (ethylsulfonyl)-2-

pyridinesulfonamide (IN-E9260) or N-(4, 6-dimethoxy-2-pyrimidinyl)-N-((3-ethylsulfonyl)-2-

pyridinyl) urea (IN-70941). IN-70941 is deamidated to form IN-70942, which is sequentially 

demethylated and hydroxylated. Excretion accounted for 93 to 96% of the administered 

radioactivity, with 58 to 67% appearing in the urine and 20 to 33% in the feces. 

4.2.1 Dermal Absorption

The dermal risk assessment was based on an oral study since a route-specific dermal toxicity 

study was not submitted for rimsulfuron. In addition, no in vivo dermal absorption studies are

available. Therefore, a conservative default dermal absorption factor of 100% was used for 

dermal risk assessment.

4.3 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, 

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

exposures and there are no concerns or residual uncertainties.

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.

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

Based on the hazard and exposure data, HED determined that the FQPA SF can be reduced to 

1x.

4.4.1 Completeness of the Toxicology Database

The toxicology database is complete for risk assessment. The existing database for FQPA 

assessment includes developmental and reproductive toxicity studies. Also, acute and 

subchronic neurotoxicity battery studies and an immunotoxicity study have been recently 

submitted and are undergoing detailed review. Detailed review of the developmental and 

reproductive studies, and initial screening of the neurotoxicity and immunotoxicity, suggests

there is no concern for neurotoxicity or immunotoxicity.

4.4.2 Evidence of Neurotoxicity

No clinical signs of neurotoxicity were observed in the available developmental, reproduction, 

immunotoxicity, subchronic or chronic studies. Acute and subchronic neurotoxicity studies are 

currently under review, and the preliminary evaluations reveal no indication of neurotoxicity.

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

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 in the presence of 

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

increased susceptibility following pre- and/or postnatal exposures.

4.4.4 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 conducted with 

DEEM-FCID utilized tolerance residues for all crops. In addition, default processing factors 

were assumed for all commodities. 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 
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concluded that the DEEM-FCID analysis does not underestimate risk from chronic exposure to 

rimsulfuron.

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

Endpoint selection and points of departure have been presented in the previous risk assessment 

(E. Holman, D384623, 11/04/11), and are summarized in Tables 4.5.4.1 and 4.5.4.2 below.

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 

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 effects seen at the 

LOAEL, increased urinary volume, kidney weights, and decreased osmolality, are not considered 

to be severe. However, the kidney is a target organ in rats and dogs (increased kidney weights, 

diueresis) following rimsulfuron exposure; also, other sufonylurea 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 
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are very similar, suggesting that the difference in NOAELs may just be a matter of dose 

selection, and thus not toxicologically significant.

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

Since the toxicological endpoints for the dermal and inhalation route of exposure are based on 

the same study and the toxicological effect are the same, the dermal and inhalation routes are 

combined together.

4.5.3 Cancer Classification and Risk Assessment Recommendation

HED determined that rimsulfuron should be classified as “Not Likely to be Carcinogenic to 

Humans.” (Jessica Kidwell, Dec 16, 2008. TXR 0052726) As such, there is no cancer risk 

associated with registered or proposed uses of rimsulfuron.

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

Assessment

Table 4.5.4.1 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.
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Table 4.5.4.1 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

Inhalation 

Term (1-30 

days);

intermediateTerm (1-6 

months)

NOAEL= 

6.25 mg/kg 

/day

UFA=10x

UFH=10x

IAF=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.

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. IAF=inhalation absorption factor (i.e., inhalation 

toxicity considered to be equivalent to toxicity via the oral route). 

5.0 Dietary Exposure/Risk Characterization

5.1 Pesticide Metabolism and Environmental Degradation

5.1.1 Metabolism in Primary Crops and Livestock

MARC Decision Memo, L. Cheng, G. Herndon, 11/FEB/1998; and DP# 200158, M. Nelson, 29/MAR/1994

MARC Briefing Memo, L. Cheng, 04/FEB/1998; and DP# 200157, M. Nelson, 17/MAR/1994

The nature of the residue in plants and livestock is sufficiently understood based on adequate

metabolism studies conducted with rimsulfuron, labeled in the pyridine or pyrimidine ring, in 

field corn, potatoes, tomatoes, lactating goats, and laying hens. 

The metabolic pathways were found to be similar in plants and livestock. The major route of 

rimsulfuron metabolism/degradation involves sulfonylurea bridge contraction, with sulfonylurea 

bridge cleavage as a minor metabolic route. The metabolites detected were IN-70941, IN-70942, 

IN-E9260, IN-J290, IN-69190 (goat), IN-H1043 (goat), IN-T5831 (potato), IN-JF999 (hen, 

tomato), and unresolved polar/nonpolar products (see Appendix C for structures). Based on the 

results of the studies, HED concluded that the residue of concern in plant and livestock 

commodities is the parent compound, rimsulfuron. 

5.1.2 Metabolism in Rotational Crops

DP# 200157, M. Nelson, 17/MAR/1994

The nature of rimusulfuron residues in rotational crops is adequately understood based on the 

previously submitted confined accumulation study in wheat. Rimsulfuron is extensively 

metabolized in rotational crops. Metabolites 1N-70941, IN-E9260, and IN-Hl043 were 

identified in the straw of wheat planted into aged (30 days and 120days), 14C-E9636 treated soil 
Rimsulfuron D391083

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and grown to maturity (Structures are provided in Appendix C). No undegraded rimsulfuron was 

detected in the straw of wheat at maturity. 

5.1.3 Analytical Methodology

DP# 330813, S. Hummel, 08/AUG/2006

DP# 326655, D. Rate, 15/MAY/2007

DP# 391764, M. Negussie, 10/JAN/2012

Enforcement methods: Currently, an HPLC/UV method exists for the enforcement of tolerances 

for residues of rimsulfuron in/on corn, potato, and tomato commodities. The method, AMR1241-88, involves extraction of samples with pH 7 potassium phosphate buffer and methanol 

(75:25, v:v). The extract is acidified to pH 2.5-3.5 (using concentrated phosphoric acid) and 

filtered for analysis by HPLC/UV with column switching, using a phenyl column for clean-up 

chromatography followed by an Rx column for analytical chromatography. The LOQ is 0.05 

ppm.

DuPont also proposed two additional methods using liquid chromatography with tandem mass 

spectroscopy (LC/MS/MS) for tolerance enforcement: Method DuPont-15033 for watery and dry 

crop matrices, and Method DuPont-15027 for oily crop matrices. These methods were also 

adequate for data collection, as shown in the submitted studies. The validated LOQ is 0.010 ppm 

in each matrix. Based on feedback from the ILV for each method, revised methods DuPont15033 and DuPont-15027 have been submitted and address all recommended changes from the 

ILV. These changes included the addition of refrigeration/homogenization periods, in order to 

reduce the degradation of rimsulfuron residues, and fixing noted typographical errors. Thus, the 

conditional data requirement from D326655 (D. Rate, 5/13/2007) has been met. 

Data-Collection methods: Chicory samples were analyzed for residues of rimsulfuron using the 

LC/MS/MS method, from DuPont Method 13412, Revision Number 1, modified to improve 

performance. 

Samples of chicory from the submitted crop field trials were analyzed using acceptable data 

collection method. The submitted LC/MS/MS method (Method 13412, Revision 1) has been 

previously reviewed in conjunction with a petition for thifensulfuron-methyl (DP# 330813, S. 

Hummel, 08/AUG/2006) for oily crop matrices. RAB3/HED has evaluated the method for 

chicory according to our SOP Number ACB-019 and found the method to be adequate for 

enforcing tolerances. The method does not require a laboratory tolerance method validation 

(TMV) trial, and can be forwarded to FDA.

5.1.4 Magnitude of the Residue in Plants

DP# 391764, M. Negussie, 10/JAN/2012

The available chicory field trial data are acceptable and reflect the proposed use patterns 

provided the directions for use are revised as specified in OPPTS 860.1200. All samples were 

analyzed for the residue of concern using an adequate method, and sample storage conditions 

and intervals were supported by the available storage stability data. The proposed tolerances 
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(0.01 ppm) in/on chicory roots and leaves are adequate. Provided the label is revised as 

requested, the proposed use pattern and label will be adequate.

5.1.5 Environmental Degradation

DP#s 358869 and 358875, J. Meléndez, 23/JAN/2009

Rimsulfuron is expected to transform/degrade into a number of transformation/degradation 

products under different environmental conditions. The three major degradates of rimsulfuron 

result from contraction or cleavage of the sulfonurea-bridge (IN-70941 and IN-70942 from 

contraction while IN-J9260 from cleavage). In contrast, the minor degradates are cleavage 

degradates (IN-J9260 is a minor degradate in systems other than aerobic soil, IN-J290 and INT5831) (structures are provided in Appendix C).

5.1.6 Comparative Metabolic Profile

In rats, rimsulfuron is excreted within the first 72 hours following dosing in the urine (~64%) 

and the feces (~30%). 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 highest percentage of the urinary (42 to 55%) and fecal (5 to 16%) radioactivity 

was attributed to unmetabolized parent compound. Metabolism involves either the contraction 

or cleavage of the sulfonylurea bridge. 

Metabolism of rimsulfuron in plants and other animals (poultry and ruminants) appears to be 

similar to its metabolism in rats. Metabolism involves either the contraction or cleavage of the 

sulfonylurea bridge. The major residue found in plants is the parent compound, rimsulfuron. 

5.1.7 Residues of Concern Summary

Table 5.1.7. 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 Not Applicable

5.1.8 Drinking Water Residue Profile

DP#s 358869 and 358875, J. Meléndez, 23/JAN/2009; DP 384624, M. Barrett, 10/27/11; DP 391086, M. Barrett, 

3/15/12
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EFED previously assessed the drinking water residue profile for rimsulfuron (DP 358869,

358875, 384624) ) for other uses which drive exposure according to the Tier 1 modeling; the 

new chicory use is at a much lower rate (i.e., maximum annual application of 0.00938 lb ai/acre 

versus 0.06250 lb ai/acre). EFED updated the previous estimates based upon a revision of the 

aerobic soil degradation rate for rimsulfuron. There is no difference in the use pattern for the 

new use on chicory that would modify the inputs for the Tier 1 modeling to the extent that the 

highest previously calculated estimated drinking water concentrations would change. The 

maximum use rate of 0.0625 lb ai/A/season for citrus, pome, stone fruit, canberry and bushberry 

that was previously assessed is more conservative that the proposed use on chicory.

Therefore, the recommended values for estimated drinking water concentrations remain 

unchanged (DP 384624). The residue of concern in drinking water is parent rimsulfuron only 

(HED MARC decision memo; 29/MAR/1994). EFED estimated the residues of rimsulfuron in 

surface water and groundwater using the FQPA Index Reservoir Screening Tool (FIRST) and 

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

their descriptions are available at the EPA internet site: 

http://www.epa.gov/oppefed1/models/water/. The maximum EDWCs are presented below in 

Table 5.1.8.

Table 5.1.8. Summary of Estimated Surface Water and Groundwater Concentrations of Rimsulfuron1.

Maximum Surface Water EDWC (ppb) Maximum Groundwater Acute/Chronic 

Acute Value Chronic/Cancer Value EDWC (ppb)

5.596 0.120 0.016

1 Degradates are not included as recommended by HED Metabolism Committee. The EDWCs were calculated 

based on the maximum application rate of 0.0625 lb ai/A/season (for citrus, pome and stone fruits, ground broadcast 

application, wetted in).

The chronic surface water EDWC was higher than the groundwater EDWC; therefore, the 

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

water value is not relevant to this dietary assessment, as a toxic effect attributable to a single 

dose has not been identified for rimsulfuron. 

5.1.9 Food Residue Profile

D385612, E. Holman, October 28, 2011

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. The proposed tolerance associated with the new uses 

of rimsulfuron on chicory (roots and tops) is 0.01 ppm. 

The unrefined chronic dietary assessment is based on the assumption that rimsulfuron residues 

are present at tolerance levels (established or recommended) in all commodities for which 

tolerances have been established and that 100% of those crops are treated. DEEMTM Version 

7.81 default processing factors were applied to all processed commodities for which they were 

available. There are no processed commodities associated with the proposed uses currently 

under review. 
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5.2 Dietary Exposure and Risk

5.2.1 Acute Dietary Exposure/Risk

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

single dose has not been identified for rimsulfuron.

5.2.2 Chronic Dietary Exposure/Risk

D394389, E. Holman, October 28, 2011

Rimsulfuron chronic dietary (food + drinking water) exposure estimates using the DEEMFCIDTM software are well below HED’s level of concern for the U.S. population and each of the 

population subgroups. Dietary exposure was estimated to be 0.000428 mg/kg bw/day for the 

U.S. population (<1% of the cPAD) and 0.001063 mg/kg bw/day (<1% of the cPAD) for the 

most highly exposed population subgroup (children, 1-2 years old). The estimated exposures 

and risks from residues of rimsulfuron in food and water are summarized in Table 5.2. This 

assessment is a conservative estimate of the dietary exposure to rimsulfuron, with the 

assumptions of 100% crop treated and tolerance-level residues for all commodities. 

Table 5.2. Chronic Aggregate Dietary (Food + Drinking Water) Exposure and Risk for Rimsulfuron.

Population Subgroup

Chronic Dietary Cancer

Dietary Exposure

(mg/kg bw/day) % cPAD Dietary Exposure(mg/kg bw/day) Risk

General U.S. Population 0.000428 <1

N/A N/A

All Infants (< 1 year old) 0.000544 <1

Children 1-2 years old 0.001063 <1

Children 3-5 years old 0.001003 <1

Children 6-12 years old 0.000686 <1

Youth 13-19 years old 0.000504 <1

Adults 20-49 years old 0.000342 <1

Adults 50+ years old 0.000254 <1

Females 13-49 years old 0.000337 <1

The values for the highest exposed population for each type of risk assessment are in bold text.

5.2.3 Cancer Dietary Risk

HED classified rimsulfuron as “not likely to be carcinogenic to humans.” Therefore, there is no 

cancer risk associated with existing or proposed uses. 
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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.

6.1.1 Spray Drift

Spray drift is a potential source of exposure for residents living in close proximity to spraying 

operations. This situation is particularly the case with aerial application. However, to a lesser 

extent, spray drift resulting from the ground application of rimsulfuron could also be a potential 

source of exposure. The Agency has been working with the Spray Drift Task Force, EPA 

Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop 

the best spray drift management practices (see the Agency’s Spray Drift website for more 

information at http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical by 

chemical basis, the Agency is now requiring interim mitigation measures for aerial applications 

that must be placed on product labels/labeling. The Agency has completed its evaluation of the 

new database submitted by the Spray Drift Task Force, a membership of U.S. pesticide 

registrants, and is developing a policy on how to appropriately apply the data and the AgDRIFT 

computer model to its risk assessments for pesticides applied by air, orchard airblast and ground 

hydraulic methods. After the policy is in place, the Agency may impose further refinements in 

spray drift management practices to reduce off-target drift with specific products with significant 

risks associated with drift.

7.0 Aggregate Risk Assessments and Risk Characterization

In accordance with the FQPA, HED must consider and aggregate rimsulfuron 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 has considered 

both the route and duration of exposure. The only exposure identified for rimsulfuron is chronic 

(food and drinking water). Because there are currently no registered residential uses for 

rimsulfuron and chronic exposures due to residential use are not expected, chronic risk is solely

due to dietary risk from food and drinking water. Section 5.2.2 describes the chronic aggregate 

risk, which is not of concern.

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 

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 
Rimsulfuron D391083

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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 Pathway

9.1 Short-and Intermediate-Term Handler Risk

The scenarios, inputs, and assumptions used for estimating exposures resulting from the 

proposed uses of rimsulfuron are summarized below: 

Exposure scenarios assessed:

- Mixing and loading BASIC®SG Herbicide for ground boom applications 

- Applying the spray mixture by a ground boom sprayer

Application equipment: Ground broadcast applications may be made with tractor drawn ground 

boom sprayers. 

Unit exposures: No chemical-specific handler exposure data were submitted in support of this 

action To assess handler exposures for regulatory actions when chemical-specific data are not 

available, HED relies on the most scientifically reliable surrogate data currently available from 

various sources such as the Office of Pesticide Handler Exposure Database (OPHED) and the 

Agricultural Handler Exposure Task Force (AHETF). Some of this data, such as the industry 

task force data, is compensatory and is subject to the data protection provisions of FIFRA. The 

HED policy on use of surrogate data is described in more detail on the Agency's website 

(http://www.epa.gov/ pesticides/science/handler-exposure-data.html). The scenario-specific 

surrogate exposure data, including their sources are presented in the “Occupational Pesticide 

Handler Unit Exposure Surrogate Reference Table” (http://www.epa.gov/pesticides/science/

handler-exposure-table.pdf). 

Exposure durations: According to the proposed label, one application on chicory is allowed per 

year at the maximum rate of 0.009 lb ai/A, resulting in short-term handler exposures. Two 

sequential applications may be made at a maximum seasonal rate of 0.009 lb ai/A/growing 

season. Since, HED typically assumes commercial applicators use rimsulfuron for longer 

durations (> 1 month), intermediate-term exposures were also assessed. Long-term exposures 

are not expected; therefore, a long-term assessment was not conducted. 

Personal Protective Equipment (PPE): Typically, HED uses a tiered approach to PPE starting 

with baseline attire (e.g., long-sleeve shirt, long pants, shoes and socks). If the estimated MOE is 

less than the LOC of 100, mitigation is applied (e.g., gloves, respirator, apron, etc.) to attain an 

MOE above the LOC. If the estimated risks continue to be of concern with maximum PPE, then 

engineering controls (e.g., enclosed cockpits and closed mixing/ loading systems), formulation 
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changes, etc. are considered. The proposed PPE includes long-sleeved shirt and long pants, 

shoes plus socks and chemical resistant gloves. 

Dermal absorption: In the absence of a dermal absorption study, HED assumed 100 % 

absorption of residues from skin; this assumption is considered to be conservative, and therefore 

dermal risks associated with rimsulfuron are considered upper-bound. 

Table 9.1 summarizes the risks associated with handler’s exposure to rimsulfuron when used in 

accordance with the proposed use pattern for weed control in chicory. The estimated risks for 

short- and intermediate-term are the same since the same endpoint and dose were used to 

estimate risks for both durations. The estimated short-term combined risks for occupational 

handlers are MOE ≥ 11,000 with an LOC of 100, and therefore the dermal and inhalation risks 

are not of concern. 
Table 9.1. Rimsulfuron - Short- and Intermediate-Term Occupational Exposure and Risk for Handlers Treating Chicory.

Scenario and (Source 

of unit exposures) PPE 1

Appl.

rate

lb ai/A

Acres 

treated

/day

Dermal

unit exp., 

μg/lb ai

Inhal.

unit exp.,

μg/lb ai

Derm. dose

mg/kg/day 2

Inhal. dose

mg/kg/day 3

Total dose

mg/kg/day 4

Sh. & Interm. 

term Total 

MOE 5

Mixing/loading sol. granules (surrogate 

DF) for gr. boom appl. (AHETF)

SL

gloves 0.009 80

51.6 8.96 0.00046 0.000081 0.00054 11,000

Applying with a ground boom sprayer 

(AHETF) 

SL,

Open cab 78.6 0.34 0.00071 0.0000031 0.00071 8,800

Abbreviations used: A= acres, AHETF = agricultural handler exposure task force, MOE = margin of exposure, OPHED = pesticide handler exposure database and 

PPE = personal protective equipment, SL=single layer. 

1. SL = Single layer PPE= long-sleeved shirt, long pants and shoes with socks. 

2. Dermal exposure (mg/kg/day) = [Appl. rate (lb ai/A) * acres treated/day * dermal unit exposure (μg/lb ai handled/day /1000)] / body wt (80 kg).

3. Inhalation exposure (mg/kg/day) = [Appl. rate (lb ai/A) * acres treated/day * inhalation unit exposure (μg/lb ai handled/day /1000)] / body wt (80 kg).

4. Total dose (mg/kg/day) is the total exposure from dermal and inhalation routes for the day.

5. Short-term Total MOE = Short-term NOAEL (dermal or inhalation NOAEL 6.25 mg/kg/day) / total dose (mg/kg/day).
9.2 Post-application Exposure and Risk

Rimsulfuron is applied as postemergence spray to control weeds in chicory. Common postapplication activities performed on commercially grown chicory fields are irrigation and 

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

Chemical-specific data relevant to post-application exposure (i.e., dislodgeable foliar residue 

(DFR) data) for the rimsulfuron proposed use were not submitted. Therefore, post-application 

exposure estimates were calculated using the standard HED ExpoSAC assumptions (i.e., default 

DFR input parameters and exposure duration) and HED transfer coefficients (SOP No. 3.1). 

HED uses a concept known as the transfer coefficient (TC) to numerically represent the postapplication exposures one would receive (generally presented as cm2

/hour). A TC is a measure 

of the residue transferred from a treated surface to a person who is doing a task or activity in a 

treated area. These values are the ratio of an exposure for a given task or activity to the amount 

of pesticide residue on treated surfaces available for transfer. HED has developed a series of 

standard TCs that are unique for a variety of job tasks or activities that are used in lieu of 

chemical- and scenario-specific data. HED used Policy 3.1 Science Advisory Council for 

Exposure Policy Regarding Agricultural Transfer Coefficients to estimate TCs for the various 

tasks that post-application workers might perform on each crop grouping. 

In the absence of chemical-specific DFR data, HED assumes that 20% of the initial application is 

available for transfer on day 0 (i.e., 12 hours after application) and that the residue dissipates at a 

rate of 10% per day. Furthermore, HED also assumes an 8 hour workday for post-application 

workers. Exposures were calculated on each day after application. Exposures and risks were 

calculated for each post-application activity.

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. Post-application Exposure and Risk use of Rimsulfuron on Chicory.

Crop

App

Rate 

(lb ai/A)

Work 

Activity

Transfer 

Coefficientsa

(cm2/hr)

Postapplication 

Dayb

DFRc

(μg/cm2)

Daily Dosed

(mg/kg/day) MOE e

Chicory

(vegetable 

root and leafy 

vegetable

0.009 scouting 210 0 0.025 0.00053 12,000

irrigation

1900 0 0.0048 1,300

a Transfer coefficient from Science Advisory Council for Exposure: Policy Memo #003 "Agricultural Transfer Coefficients," 

06/03/2011.

b Day after treatment represents approximately 12 hours following application when sprays have dried.

c DFR = Application Rate (lb ai/acre) x Fraction of active ingredient that remains on the foliage when sprays have dried x 4.54E8 μg/lb 

x 24.7E-9 acre/cm2.

d Daily dose = DFR (μg/cm2) x TC (cm2/hr) x conversion factor (1 mg/1,000 μg) x exposure time (8 hrs/day) x dermal absorption 

(100%) / body weight (80 kg).

e MOE = NOAEL (6.25 mg/kg/day) / daily dose (mg/kg/day).
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Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for rimsulfuron at this time. However, volatilization of pesticides 

may be a potential source of post-application inhalation exposure to individuals nearby to 

pesticide applications. The Agency sought expert advice and input on issues related to 

volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

Scientific Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final report 

on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html) and is 

in the process of evaluating the SAP report. The Agency may, as appropriate, develop policies 

and procedures to identify the need for and, subsequently, the way to incorporate postapplication inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative post-application 

inhalation exposure assessment for rimsulfuron.

9.3 Restricted Entry Interval (REI) 

The currently registered product label lists a REI of 4 hours. PR Notice 95-03 on the Reduced 

REI policy (3-May-1995) does not list rimsulfuron as an active ingredient approved for a 4-hour 

REI. However, PR 95-03 allows a 4-hour REI provided that end-use products meet the 

following reduced risk criteria:

1) The end-use product is in Toxicity Category III or IV for all of the following acute toxicity 

studies: acute dermal toxicity, acute inhalation toxicity, primary skin irritation, and primary eye 

irritation.

2) Based on the required sensitization or hypersensitivity studies, the end use product is not a 

sensitizer, and there have been no reports of hypersensitivity.

3) The registrant has no data indicating, and is not aware of, adverse health effects associated 

with the end use product, e.g., carcinogenicity, neurotoxicity, developmental effects or 

reproductive effects.

4) The registrant is not aware and has not been informed of incident information (illness or 

injury reports) that are “definitely” or “probably” (as defined by the California Incident 

Reporting System) related to post application exposures to the product.

The label REI is typically based on the acute toxicity of technical chemical. Under the worker 

protection standard (WPS), active ingredients classified as Toxicity Category IV for Acute 

Dermal and Primary Skin Irritation are assigned a 4-hour REI; therefore, the 4-hour REI on the 

proposed label is acceptable.

10.0 Data Needs and Label Recommendations

10.1 Toxicology

None
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10.2 Residue Chemistry

None

10.3 Occupational and Residential Exposure

None

11.0 References:

DP# 365798, D. Dotson, 13/AUG/2009

DP# 360852, D. Rate, 13/AUG/2009

MARC Decision Memo, L. Cheng, G. Herndon, 11//FEB/1998; and DP# 200158, M. Nelson, 

29/MAR/1994

MARC Briefing Memo, L. Cheng, 04/FEB/1998; and DP# 200157, M. Nelson, 17/MAR/1994

DP# 200157, M. Nelson, 17/MAR/1994

DP# 330813, S. Hummel, 08/AUG/206

DP# 326655, D. Rate, 15/MAY/2007

DP#s 358869 and 358875, J. Meléndez, 23/JAN/2009

DP# 385612, E. Holman, Oct 2011

DP# 394389, E. Holman, Oct. 2011

DP# 391764, M. Negussie, 10/JAN/2012

D399026, C. Walls, April 2012
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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) <10-5Pa

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: Toxicology Assessment

B.1 Toxicity Profiles

Table B.1.1 Acute Toxicity Profile – Rimsulfuron

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

870.1100 Acute oral Rat

Acute oral Mouse

41356311, 

41356310,41

931634

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;4

1931637;41

931636;

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, 

41356318,41

931639, 

41356317 

No irritation IV

870.2600 Skin sensitization Guinea Pig 41931628, 

41356320, 

41931641, 

41931640,41

356319

Not a sensitizer IV

Table B.1.2 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)/ 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.
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Table B.1.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No./ Study 

Type

MRID No. (year)/ Classification /Doses Results

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

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.
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Table B.1.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No./ Study 

Type

MRID No. (year)/ Classification /Doses Results

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)/ 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, 

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 
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Table B.1.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No./ Study 

Type

MRID No. (year)/ Classification /Doses Results

or 1.1 mg/mL silver grain counts] was induced.

870.6200a

Acute Neurotoxicity 

(rat)

48710302 (2011)

0, 200, 1000, 2000 mg/kg

NOT YET CLASSIFIED – study under 

review

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)

NOT YET CLASSIFIED – study under 

review

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

NOT YET CLASSIFIED – study under 

review

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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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
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Appendix D: Review of Human Research

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

intentionally exposed to a pesticide to determine their dermal and inhalation exposure. Many 

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

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

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

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

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

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

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

regulatory barrier to continued reliance on these studies.
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Appendix E. International Residue Limit Status Sheet

Rimsulfuron (PC Code 129009; 12/05/2011)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition: Rimsulfuron 

US Canada Mexico2 Codex3

40 CFR 180.478:

Plant/Livestock: rimsulfuron, N-((4,6-

dimethoxypyrimidin-2-

yl)aminocarbonyl)-3-(ethylsulfonyl)-

2-pyridinesulfonamide)

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

pyrimidinyl)amino]carbo

nyl]-3-

(ethylsulfonyl)-2-

pyridinesulfonamide

None

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

US Canada Mexico2 Codex3

Chicory, roots 0.01

Chicory, tops 0.01

Completed: M. Negussie; 12/05/2011

1

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

not those proposed by the applicant.

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

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

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

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