UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY 

AND

POLLUTION PREVENTION

November 4, 2011

MEMORANDUM

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

Caneberry and Bushberry. 

PC Code: 129009 DP Barcode: D384623, D386178

Decision No.: 4427470 and 443815 Registration No.: 352-768

Petition No.: 0E7809 Regulatory Action: Section 3

Assessment Type: Single Chemical Aggregate Registration Case 

No.:

NA

TXR No.: NA CAS No.: 122931-48-0

MRID No.: NA 40 CFR: §180.478

FROM: Elizabeth Holman, Chemist/Risk Assessor

S. Oonnithan, Biologist

Risk Assessment Branch II

Health Effects Division (HED) (7509P)

THROUGH: Karlyn Middleton, Toxicologist

Christina Swartz, Branch Chief

Risk Assessment Branch II

Health Effects Division (7509P)

TO: Sidney Jackson, Review Manager

Barbara Madden, Minor Use Team Leader

Risk Integration Minor Use, and Emergency Response Branch

Registration Division (7508P)

The Registration Division (RD) requested that the Health Effects Division (HED) conduct a risk 

assessment for the active ingredient rimsulfuron to estimate the risk to human health that will 

result from the proposed use to control broadleaf weeds in bushberry and caneberry. 
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Table of Contents

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

2.0 Ingredient Profile .............................................................................................................. 9

2.1 Proposed Use Directions....................................................................................... 9

2.2 Structure and Nomenclature ............................................................................. 10

2.3 Physical and Chemical Properties..................................................................... 10

3.0 Hazard Characterization/Assessment........................................................................... 11

3.1 Hazard and Dose-Response Characterization.................................................. 11

3.1.1 Database Summary................................................................................. 11

3.1.2 Toxicological Effects............................................................................... 12

3.2 Absorption, Distribution, Metabolism, Excretion (ADME)............................ 13

3.3 FQPA Considerations......................................................................................... 13

3.3.1 Adequacy of the Toxicity Database ....................................................... 13

3.3.2 Evidence of Neurotoxicity ...................................................................... 14

3.3.3 Developmental Toxicity.......................................................................... 14

3.3.4 Reproductive Toxicity ............................................................................ 14

3.3.5 Pre-and/or Postnatal Toxicity................................................................ 14

3.3.6 Recommendation for a Developmental Neurotoxicity Study.............. 15

3.3.7 FQPA Safety Factor for Infants and Children..................................... 15

3.4 Hazard Identification and Toxicity Endpoint Selection.................................. 15

3.4.1 Acute Reference Dose (aRfD) – Females Ages 13-49 and General 

Population............................................................................................................ 15

3.4.2 Chronic Reference Dose (cRfD)............................................................. 16

3.4.3 Dermal Absorption ................................................................................. 16

3.4.4 Dermal Exposure (Short-, Intermediate-Term)................................... 16

3.4.5 Inhalation Exposure (Short-, Intermediate-Term).............................. 17

3.4.6 Level of Concern for Margin of Exposure............................................ 17

3.4.7 Recommendation for Aggregate Exposure Risk Assessments............ 18

When there are potential occupational and residential exposures to a pesticide, the risk 

assessment must address exposures from three major sources: oral, dermal and inhalation 

exposures, and determine whether the individual exposures can be combined if they have 

the same toxicological effects. For rimsulfuron, short-/intermediate-term dermal and 

inhalation exposure and risk are being assessed based on the same endpoint and dose 

from the oral study in the dog. Therefore, these routes of exposure can be combined. .. 18

3.4.8 Classification of Carcinogenic Potential ............................................... 18

3.4.9 Summary of Toxicological Doses and Endpoints for Rimsulfuron for 

Use in Human Risk Assessments....................................................................... 18

4.0 Public Health and Pesticide Epidemiology Data.......................................................... 19

5.0 Dietary Exposure/Risk Characterization ..................................................................... 19

5.1 Pesticide Metabolism and Environmental Degradation.................................. 19

5.1.1 Metabolism in Primary Crops and Livestock ...................................... 19

5.1.2 Metabolism in Rotational Crops............................................................ 20

5.1.3 Analytical Methodology.......................................................................... 20

5.1.4 Magnitude in Plants................................................................................ 20

5.1.5 Environmental Degradation .................................................................. 21

5.1.6 Comparative Metabolic Profile ............................................................. 22
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5.1.7 Pesticide Metabolites and Degradates of Concern............................... 22

5.1.8 Drinking Water Residue Profile ............................................................ 22

5.1.9 Food Residue Profile............................................................................... 23

5.1.10 International Residue Limits................................................................. 23

5.2 Dietary Exposure and Risk ................................................................................ 24

5.2.1 Acute Dietary Exposure/Risk................................................................. 24

5.2.2 Chronic Dietary Exposure/Risk............................................................. 24

5.2.3 Cancer Dietary Risk ............................................................................... 24

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................ 24

6.1 Other (Spray Drift, etc.)..................................................................................... 25

7.0 Aggregate Risk Assessments and Risk Characterization............................................ 25

8.0 Cumulative Risk Characterization/Assessment........................................................... 25

9.0 Occupational Exposure/Risk Pathway.......................................................................... 25

9.1 Short-Term Handler Risk .................................................................................. 26

9.2 Postapplication Exposure and Risk................................................................... 29

9.3 Restricted Entry Interval (REI) ........................................................................ 29

10.0 Data Needs and Label Recommendations .................................................................... 30

10.1 Toxicology............................................................................................................ 30

10.2 Residue Chemistry.............................................................................................. 30

10.3 Occupational and Residential Exposure........................................................... 30

References:................................................................................................................................... 30

Appendix A: Toxicology Assessment ....................................................................................... 31

A.1 Toxicity Profiles....................................................................................................... 31

A.2 Rationale for Toxicology Data Requirements. ..................................................... 34

Appendix B: Tolerance Setting.................................................................................................. 37

Appendix C: Review of Human Research ................................................................................ 37
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1.0 Executive Summary

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

synthase (ALS). Inhibition of the enzyme leads to rapid cessation of growth and visual 

symptoms such as chlorosis, necrosis, leaf malformation and discoloration. These effects appear 

a few days after treatment in sensitive species. 

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

on caneberry and blueberry (PP# OE7809), and has proposed the establishment permanent 

tolerances for residues of rimsulfuron in the caneberry subgroup (13-07A) and the blueberry 

subgroup (13-07B), both at 0.01 ppm.

The proposed uses to be added to Dupont’s Matrix® SG Herbicide (EPA Reg. No. 352-768) 

include broadcast spray and band treatment applications of rimsulfuron to be applied to 

bushberry and caneberry at a maximum single application rate of 0.063 lb ai/A (4.0 oz/A). For 

band treatments, an additional application is permitted 30 days after the original application but 

the total application rate cannot exceed 0.063 lb ai/A/yr (4.0 oz/A/yr). A maximum of two split

applications are allowed per year. Handlers may apply rimsulfuron using ground equipment. 

Based on the proposed use pattern, HED has assessed short- and intermediate-term occupational 

exposure for handlers; however, postapplication exposure was not assessed due to the low 

expectation for exposure via dermal and inhalation routes for workers who re-enter treated areas.

Toxicity/Hazard

For the proposed new uses, the toxicological database for rimsulfuron is adequate for risk 

assessment purposes. However, in accordance with the new part 158 guidelines, acute and 

subchronic neurotoxicity, immunotoxicity and 21/28 day dermal toxicity studies are required. 

In the available toxicity studies, there was no evidence of neurotoxicity or treatment-related 

effects on the immune system. Additionally, there is no concern for increased susceptibility of 

the young and a developmental neurotoxicity study in not required at this time. Based on the 

weight of the evidence, HED does not believe that the submission of the required studies will 

result in lower points of departure (POD) than those currently used for overall risk assessment. 

Therefore, the available studies are considered adequate for the purposes of dose/endpoint 

selection and hazard characterization and additional safety factors are not needed. 

In subchronic and chronic toxicity studies in rats, toxic effects included decreased body weight, 

decreased body weight gain, increased relative liver and absolute kidney weights, and diuresis 

(increased urine) at ≥ 375 mg/kg bw/day. At 500 mg/kg bw/day, 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 at ≥ 121/568 mg/kg 

bw/day (M/F). Increased mortality was observed at 414 mg/kg bw/day 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 at ≥ 225 mg/kg bw/day. After chronic exposure at 1127/1505 

mg/kg bw/day (M/F), 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 
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weights accompanied by decreased urinary osmolality was observed ≥ 125 mg/kg bw/day 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 ≥ 81.8 mg/kg bw/day in males. At 342.4/358.5 mg/kg 

bw/day (M/F), 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, and in the two generation study in 

rats, developmental/offspring toxicity was seen in the presence of maternal/systemic toxicity 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. Although the acute and subchronic neurotoxicity studies are now required, there 

was no evidence of potential neurotoxicity in the submitted studies, and HED has concluded that 

a developmental neurotoxicity study is not needed. Based on the low concerns for pre- and/or 

postnatal susceptibility and the lack of potential immunotoxic effects, HED has concluded that 

the FQPA Safety Factor should be reduced to 1X.

The endpoint for chronic dietary risk assessment was chosen from the rat chronic/carcinogenicity 

study, and was based on liver and body weight effects. The endpoint for dermal and inhalation 

risk assessment for occupational workers was chosen from the 90-day oral study in the dog, and 

was based on kidney effects.

It was determined that rimsulfuron should be classified as “Not Likely a Human Carcinogen,”

based on the lack of evidence for carcinogenicity in studies conducted in rats and mice. 

Rimsulfuron is not mutagenic. It has low acute oral, dermal and inhalation, but is a moderate eye 

irritant. It is not a dermal sensitizer.

Residue Chemistry

The residue chemistry database is complete and there are no residue chemistry issues associated 

with the requested new uses on caneberry and bushberry. The nature of the residue in plants and 

livestock is adequately understood based on acceptable metabolism studies conducted with 

rimsulfuron, labeled in the pyridine or pyrimidine ring, in field corn, potatoes, tomatoes, 

lactating goat, and laying hen. HED previously concluded that rimsulfuron is the residue of 

concern for both regulatory and risk assessment purposes in both plant and animal commodities. 

HED is recommending for the establishment of permanent tolerances for the requested crops. 

No quantifiable residues were observed in the submitted crop field trials for the proposed uses. 

Therefore, the recommended tolerances of 0.01 ppm are based on the limit of quantitation (LOQ) 

of the analytical method. Suitable analytical methods are available to enforce tolerances for 

residues of rimsulfuron. 

Under a separate submission (DP 386178, Decision No. 443815), the registrant has submitted 

revised analytical enforcement methods in order to fulfill conditional data requirements 

previously identified (DP 326655). HED has reviewed these revised methods, which were 
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needed to address problems identified by the independent laboratory validation, and determined 

that all issues have been addressed. Thus, this conditional data requirement has been met. 

Dietary Exposure (food/water)/Risk Characterization:

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

population and all population subgroups. An acute dietary assessment was not performed, as a 

toxicological endpoint attributable to a single dose has not been identified for rimsulfuron. Also, 

rimsulfuron is classified as “not likely” to be carcinogenic; therefore, there is no cancer risk 

associated with exposure to rimsulfuron.

Residential Exposure

There are currently no residential uses for rimsulfuron, and therefore no non-occupational 

exposure is expected to result from the proposed and labeled uses.

Aggregate Risk

Because there is no residential exposure and no acute dietary endpoints were identified, the

aggregate risk for rimsulfuron is equivalent to chronic dietary (food and drinking water) risk. As 

with the chronic dietary risk, the aggregate risk associated with the proposed and registered uses 

of rimsulfuron is significantly below HED’s level of concern.

Occupational Exposure/Risk

No chemical-specific data were submitted in support of the proposed uses. Therefore, for 

handlers HED used standard assumptions with respect to the typical work day, the standard adult 

body weight, area treated per day, and surrogate unit exposures from the Occupational Pesticide 

Handler Unit Exposure Surrogate Reference Table (OPHED) and from the Outdoor Residential 

Exposure Task Force (ORETF). The amount applied was based on the proposed label rates and 

use pattern. A postapplication dermal exposure assessment was not conducted because the label 

recommends using a directed spray application for weed control on berries while minimizing 

contact with crop foliage. In addition, the label recommends timing application with rainfall or 

watering-in to maximize herbicidal effectiveness. Therefore negligible dermal exposure is 

expected for postapplication workers re-entering treated areas.

For handlers, the estimated short- and intermediate-term combined dermal and inhalation 

margins of exposure (MOE) ranged from 370 to 3,000. HED's level of concern (LOC) is an 

MOE less than 100, and therefore the estimated risks for handlers applying rimsulfuron to bushand caneberries are not of concern. A quantitative postapplication inhalation exposure 

assessment was not conducted, primarily due to the very low exposure expected based on the use 

pattern and the vapor pressure of rimsulfuron, and there is also no concern for workers who re-
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enter treated areas. Handler MOEs for inhalation exposure are considered to be protective of 

postapplication exposure and risk via the inhalation route.

Review of Human Research:

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

intentionally exposed to a pesticide or other chemical. These studies, which comprise the 

Occupational Pesticide Handlers Exposure Database (OPHED) 

(http://www.epa.gov/pesticides/science/handler-exposure-data.html and

http://www.epa.gov/pesticides/science/post-app-exposure-data.html) have been determined to 

require a review of their ethical conduct, have received that review, and have been determined to 

be ethically conducted.

HED Recommendations:

There are no residue chemistry, toxicology, or risk issues that would preclude granting a 

registration for uses of rimsulfuron (25% water dispersible granule (WDG) formulation; 

DuPontTM Matrix ® SG Herbicide (EPA No. 352-768)) on caneberry and blueberry.

Additional Data Needs:

Toxicology

The following toxicity studies are outstanding: acute and subchronic neurotoxicity, 

immunotoxicity, and 21/28 day dermal toxicity studies. These data requirements were 

previously noted in the 2009 risk assessment (DP360852, D. Rate, 13/AUG/2009). Progress 

towards meeting these requirements is being made, including EPA receipt of the proposal for the 

rimsulfuron immunotoxicity testing regarding species and dose selection to fulfill the 870.7800 

guideline study. This proposal has been reviewed by HED (D384959, J. Kidwell, 5/Jan/2011) 

and the registrant should incorporate these recommendations into their forthcoming 

immunotoxicity data submission. These additional data requirements do not preclude making 

the safety finding for this risk assessment, as the toxicological database is adequate to allow a 

sufficiently protective assessment.

Residue Chemistry

No additional data are needed. Previously required conditional data have been reviewed and 

considered acceptable.

Occupational/Residential

No additional data are needed.

Tolerance Considerations

Enforcement Analytical Method

Currently, an 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 
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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. 

International Harmonization

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

rimsulfuron. However, there is a Canadian MRL of 0.05 ppm for rimsulfuron residues on 

blueberry, based on their method LOQ of 0.05 ppm and no residues above LOQ being observed 

in their reviewed field trials. Given the availability of a more sensitive analytical method with an 

LOQ of 0.01 ppm, HED recommends proceeding with setting a tolerance for the bushberry crop 

group of 0.01 ppm, which includes the blueberry commodity. With PMRA having only a 

tolerance on blueberry of 0.05 ppm, if USEPA were to harmonize tolerances on this commodity, 

this would result in an inconsistency with the remaining commodities in the bushberry crop 

group.

Recommended Tolerances

HED recommends for the following permanent tolerances:

Caneberry, subgroup 13-07A........................................................0.01 ppm

Blueberry, subgroup 13-07B.........................................................0.01 ppm

In addition, in order to ensure that legal uses of rimsulfuron under FIFRA do not result in illegal 

residues in food under the FFDCA, HED recommends for the following tolerance expression to 

be implemented for rimsulfuron under 40 CFR 180.478:

(a) General. 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 

rimsulfuron (N -((4,6-dimethoxypyrimidin-2-yl)aminocarbonyl)-3-(ethylsulfonyl)-2-

pyridinesulfonamide).

Revisions to Petitioned-For Tolerances

The only revision is the recommended change in the tolerance expression, as described above.

Label Recommendations

The supplemental label for the proposed uses is acceptable and does not require any changes. 
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The personal protective equipment (PPE) recommended on the label is considered appropriate, 

as is the Restricted Entry Interval (REI) of 4 hours.

2.0 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. 

2.1 Proposed Use Directions

The IR-4 has submitted a Supplemental Label of Matrix®SG Herbicide for use on bush- and 

caneberries. The proposed use pattern is summarized in Table 2.1.

Table 2.1: Proposed Uses of Rimsulfuron.

Product 

(EPA Reg. No.)

Use Site Application 

Method

Maximum 

Single 

Application 

Rate†

Timing of 

Application/Specifications

Commercial Products

DUPONT 

MATRIX SG 

HERBICIDE

(352-768)

25% ai

Water Soluble 

Granule

Bushberry Subgroup 13-07B;

Caneberry Subgroup 13-07A

Ground 

(Broadcast and 

band treatments) 

0.0625 lb ai/A

(Broadcast = 4.0 

oz prod/A)

(Perimeter/Band 

= 2.0 oz prod/A)

Max Application Rate/Yr = 4.0 

oz/A/year.

Max of 2 apps/year when applied 

as band treatment.

REI = 4 hrs.

Do not apply this product by air. 

Use ground application

equipment only.

Use a minimum of 10 gallons of 

spray solution per acre.

PHI = 21 days.

Allow a minimum of 30 days

between applications.

† Max Single Application Rate = (4 oz prod/A) (1 lb/16 fl oz)(25% ai) = 0.0625 lb ai/A.

Rimsulfuron may be applied for the control of grass and broadleaf weeds once at 0.063 lb 

ai/A/year or as two split applications with a 30 day interval. However, no more than 0.063 lb 

ai/A may be applied per year.

Personal Protective Equipment (PPE): The PPE for Matrix®SG Herbicide is long-sleeved 

shirt, and long pants, shoes plus socks, and chemical resistant gloves (Category A,such as butyl 

rubber, natural rubber, neoprene rubber, or nitrile rubber, all >14 mils). The restricted entry 

interval (REI) for rimsulfuron is 4 hours.

Conclusions. The label directions are adequate to allow evaluation of the residue data relative to 

the labeled uses. The available caneberry and blueberry data support the proposed 21-day PHI 

for all berry commodities. It is noted that while all blueberry field trials were conducted with an 
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adjuvant (non-ionic surfactant or crop oil concentrate), none of the caneberry trials included an 

adjuvant. The label directions include no discussion of the use of adjuvant for the proposed 

commodities. However, HED finds the blueberry data adequate for representation of the impact 

of adjuvants and therefore no prohibition of the use of adjuvant on caneberry is required. See 

Section 5.1.4 for further discussion. 

2.2 Structure and Nomenclature

Table 2.2. Rimsulfuron Nomenclature.

Compound

Common name Rimsulfuron

Company experimental name DPX-E9636

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

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

pyridinesulfonamide

CAS registry number 122931-48-0

End-use product (EP) 25% WDG (Resolve TM SG Herbicide; EPA Reg. No. 352-748)

2.3 Physical and Chemical Properties

Table 2.3. 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

N S

O

N

O H

N

H

O N

N OCH3

OCH3

SO2C2H5
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Table 2.3. Physicochemical Properties of Rimsulfuron

Parameter Value Reference

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)

2.4 Consideration of Environmental Justice 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

for toddlers, youths, and adults entering or playing on treated areas postapplication are evaluated. 

Further considerations are currently in development as OPP has committed resources and 

expertise to the development of specialized software and models that consider exposure to 

bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific 

subgroups.

3.0 Hazard Characterization/Assessment

3.1 Hazard and Dose-Response Characterization

3.1.1 Database Summary

3.1.1.1 Studies available and considered (animal, human, general literature)

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; two gene mutation assays (bacterial or 

mammalian cells in culture); an in vivo mammalian cytogenetics study in mouse; an in vitro

mammalian cytogenetics study in human lymphocytes; an unscheduled DNA synthesis (UDS) 

assay in primary rat hepatocyte cultures; a metabolism study; a combined chronic 

toxicity/carcinogenicity study in rats and a carcinogenicity study in mice.
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3.1.1.2 Sufficiency of studies/data

For the proposed new uses, the toxicological database for rimsulfuron is adequate for risk 

assessment purposes. However, in accordance with the new part 158 guidelines, acute and 

subchronic neurotoxicity, immunotoxicity and 21/28 day dermal toxicity studies are required. 

In the available toxicity studies, there was no evidence of neurotoxicity or treatment-related 

effects on the immune system. Additionally, there is no concern for increased susceptibility of 

the young and a developmental neurotoxicity study in not required at this time. 

An inhalation toxicity study is not available for rimsulfuron. As a result, an oral toxicity study in 

dogs was used to assess inhalation exposure. To better characterize the potential hazard and 

portal of entry effects from inhalation exposure, an inhalation toxicity study would be needed. 

However, since potential inhalation exposure is low, and the Margins of Exposure (MOEs) 

calculated using the NOAEL from the oral study are high, an inhalation toxicity study is not 

required at this time. The need for an inhalation toxicity study may be revisited during 

registration review. 

Based on the weight of the evidence, HED does not believe that the submission of the required 

studies will result in lower points of departure (POD) than those currently used for overall risk 

assessment. Therefore, the available studies are considered adequate for the purposes of 

dose/endpoint selection and hazard characterization and additional safety factors are not needed. 

3.1.2 Toxicological Effects

The database indicates that target organs for rimsulfuron are the liver and kidney. In subchronic

toxicity studies in rats, decreased body weight, body weight gain, increased relative liver and 

absolute kidney weights, and diuresis were observed at doses ≥ 375 mg/kg bw/day. At 500 

mg/kg bw/day, decreased liver enzymes and bilirubin, fatty change, and hepatocellular 

hypertrophy were observed in dogs. In chronic rat studies, decreased body weight gain, and 

increased liver weights were observed at ≥ 121/568 mg/kg bw/day (M/F). Increased mortality 

was observed at 414 mg/kg bw/day 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 

at ≥ 225 mg/kg bw/day. After 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 at 1127/1505 mg/kg bw/day (M/F). In dogs, diuresis indicated by 

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

urinary osmolality was observed at ≥ 125 mg/kg bw/day 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 

≥ 81.8 mg/kg bw/day in males. At 342.4/358.5 mg/kg bw/day (M/F) 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.
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In the developmental toxicity study in rats, no developmental toxicity was seen at the highest 

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

rats, developmental and offspring toxicity were seen in the presence of maternal/systemic 

toxicity at the same dose levels. Consequently, there is no evidence of quantitative or qualitative 

increased susceptibility following pre- and/or postnatal exposures and there are no concerns or 

residual uncertainties.

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. It has low acute oral, dermal and inhalation 

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

3.1.3 FQPA

The database is considered adequate to characterize any potential for prenatal or postnatal 

susceptibility for infants and children.

3.2 Absorption, Distribution, Metabolism, Excretion (ADME)

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

groups were treated once by oral gavage with 25 mg/kg 14C -pyridine-labeled compound and the 

high dose groups with 250 mg/kg of either 14C -pyridine- or 

14C-pyrimidine-labeled compound. 

The repeat dose groups were gavaged orally with unlabeled test compound (25 mg/kg) for 14 

consecutive days, followed on the 15th day by 25 mg/kg of 14C -pyridine-test compound. 

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. 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 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.

3.3 FQPA Considerations

3.3.1 Adequacy of the Toxicity Database

The toxicology database for rimsulfuron is adequate to characterize potential pre- and/or postnatal susceptibility for infants and children. Acceptable/guideline studies for developmental 

toxicity in rats and rabbits and a 2-generation reproduction study in rats were available for FQPA 

assessment. As part of the new part 158 guidelines, acute and subchronic neurotoxicity studies, 

an immunotoxicity study, and a 21/28 day dermal toxicity study are required. However, based 

on the toxicology data, additional safety factors are not needed to account for the lack of these 

studies
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3.3.2 Evidence of Neurotoxicity

No evidence of neurotoxicity was observed in the available developmental, reproduction, 

subchronic or chronic studies. Acute and subchronic neurotoxicity studies are required based on 

the latest guideline requirements. 

3.3.3 Developmental Toxicity

In an acceptable prenatal developmental study in rats, pregnant females were given rimsulfuron 

by gavage at dose levels of 0, 200, 700, 2000 or 6000 mg/kg bw/day during gestation days 7 

through 16. A NOAEL was not established for either maternal or developmental toxicity, as no 

maternal or offspring effects were observed at the highest dose tested of 6000 mg/kg bw/day.

In an acceptable prenatal developmental toxicity study in rabbits, pregnant New Zealand White 

rabbits received rimsulfuron by gavage at dose levels of 0, 25, 170, 500, or 1500 mg/kg bw/day 

during gestation days 7 through 19. In the rabbit study, maternal toxicity was observed at a 

lower dose than that which caused developmental toxicity. The NOAEL for maternal toxicity 

was 170 mg/kg bw/day and the LOAEL was 500 mg/kg bw/day based on mortality, abortion and 

decreased body weight. For developmental toxicity, the NOAEL was 500 mg/kg bw/day and the 

LOAEL was 1500 mg/kg bw/day as there were only 2 viable pups at 1500 mg/kg bw/day. The 

pup mortality was a result of increased mortality in dams at 1500 mg/kg bw/day

3.3.4 Reproductive Toxicity

In an acceptable two-generation reproduction study, rats were fed diets containing rimsulfuron at 

dose levels equivalent to 0, 2.8, 165 or 830 mg/kg bw/day for F0 males; 0; 3.4, 204 or 1021 

mg/kg bw/day for F0 females; 0, 3.7, 217 or 1316 mg/kg bw/day for F1 males; and 0, 4.3, 264 or 

1316 mg/kg bw/day for F1 females, respectively.

For parental systemic toxicity, the NOAEL was 165/204 mg/kg bw/day in males/females and the 

LOAEL was 830/1021 mg/kg bw/day in males/females based on decreased body weight gain.

Similar effects were observed in offspring at similar or slightly higher doses. For offspring 

toxicity, the NOAEL was 217/264 mg/kg bw/day in males/females and the LOAEL was 1316 

mg/kg bw/day based on decreased mean body weight in F1 males, decreased body weight gain in 

F1 females, decreased mean pup weight of the F2 females, decreased daily food consumption in 

F1 males, and decreased mean number of male F1 pups. Decreased weight was also the key 

finding for systemic effects. Thus, the toxic effects in offspring occurred at the same dose level 

as the systemic parental effects.

3.3.5 Pre-and/or Postnatal Toxicity

3.3.5.1 Determination of Susceptibility
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In the developmental toxicity study in rats, no developmental toxicity was seen at the highest 

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

rats, developmental and offspring toxicity 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.

3.3.5.2 Degree of Concern Analysis and Residual Uncertainties for Pre and/or Post-natal 

Susceptibility

There are no concerns, nor residual uncertainties for pre- and/or postnatal toxicity since there 

was no indication of increased susceptibility of rats or rabbits to in utero and/or postnatal 

exposure to rimsulfuron in the data provided. 

3.3.6 Recommendation for a Developmental Neurotoxicity Study

There is no evidence to support requiring a developmental neurotoxicity study. Neither the 

subchronic or chronic toxicity studies in rats and dogs, the developmental toxicity studies in rats 

and rabbits, nor the 2-generation reproduction study indicated that the nervous system was 

specifically affected by treatment with rimsulfuron. Acute and subchronic neurotoxicity studies 

are required by the most recent guidelines and are considered to be data gaps. 

3.3.7 FQPA Safety Factor for Infants and Children

Based on the hazard and exposure data, HED determined that the FQPA SF can be reduced to 1x 

because:

There is no evidence of increased susceptibility following in utero and/or postnatal 

exposure in the developmental toxicity studies in rats or rabbits, and in the 2-generation 

rat reproduction study; and there are no residual uncertainties concerning pre- and 

postnatal toxicity.

Although the ACN and SCN are considered to be required under the current guidelines, 

there are no concerns for neurotoxicity based on the available data and a DNT is not 

required. 

The chronic dietary food exposure assessment utilizes tolerance level residues from field 

trial data and 100 percent crop treated data for all commodities. 

Conservative surface water modeling estimates were used. 

The assessments are based on reliable data and will not underestimate exposure/risk for 

rimsulfuron. There is no potential for residential exposure.

Despite the requirement for immunotoxicity and neurotoxicity studies, there is no 

evidence that rimsulfuron either causes neurotoxic effects or directly targets the immune 

system, and therefore an additional uncertainty factor is not needed to account for the 

lack of these studies.

3.4 Hazard Identification and Toxicity Endpoint Selection

3.4.1 Acute Reference Dose (aRfD) – Females Ages 13-49 and General Population
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There were no toxicological effects attributable to a single dose observed in oral toxicity studies 

including the developmental toxicity studies in rats and rabbits. Therefore, a dose and endpoint 

were not selected for this risk assessment.

3.4.2 Chronic Reference Dose (cRfD)

Study Selected: Combined Chronic/Carcinogenicity – Rat (870.4100)

MRID No. 42047101

Dose/Endpoint for establishing the RfD: The dose selected for risk assessment is the NOAEL of 

11.8 mg/kg bw/day based on decreased body weight gains and liver effects at the LOAEL of 121 

mg/kg bw/day.

Executive Summary: In a combined chronic/ carcinogenicity study in rat, rimsulfuron (purity: 

98.8%; batch # 58246-69-1 thru 6) was given to Cr1:CD BR rats for two years at dietary 

concentrations of 25, 300, 3000, and 10000 ppm (1.00, 11.8, 121, and 414 mg/kg/day (males); 

1.38, 17.1, 163, and 569 mg/kg/day (females), respectively). The LOAEL for males and females 

is based on decreased body weight gain and liver effects. The LOAEL for males is 121 

mg/kg/day (NOAEL=11.8 mg/kg/day). The LOAEL for females is 568 mg/kg/day (NOAEL 

=163 mg/kg/day). 

Comments about Study and Endpoint: The NOAEL selected for risk assessment represents the 

lowest available NOAEL for effects of rimsulfuron following long-term dietary administration; 

therefore, it is protective of potential toxic effects. 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. 

Uncertainty Factor (UF): 100X (10X for inter-species extrapolation and 10X for intra-species 

variation). Because the FQPA Safety Factor has been reduced to 1X, the reference dose and the 

chronic population adjusted dose (cPAD) are the same.

Chronic Reference Dose (cRfD) = 11.8 mg/kg bw/day (NOAEL) = 0.118 mg/kg bw/day 

100 (UF)

3.4.3 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, a dermal absorption study is not available. 

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

assessment.

3.4.4 Dermal Exposure (Short-, Intermediate-Term)

Study Selected: 90 Day Toxicity-Dog
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MRID No. 41356322 

Dose and Endpoint for Risk Assessment: The dose selected for risk assessment is the NOAEL of 

6.25 mg/kg bw/day based on increased urinary volume, kidney weights, and osmolality at the 

LOAEL of 125 mg/kg bw/day.

Executive Summary: In a 90 day toxicity study in dogs, rimsulfuron (purity: 98.8%; batch # 17, 

463) was given to beagle dogs in the diet at 0, 250, 5000, 20000 ppm (0, 6.25, 125, or 500 mg/kg 

bw/day). Diuresis was the most notable effect observed and was indicated by increased urinary 

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

in mid and high dose dogs of both sexes. Adaptive change in the liver was evident in mid and 

high dose dogs of both sexes as indicated by increased relative and absolute liver weights, 

alkaline phosphatase activity and cholesterol content. On the basis of body weight decrement, 

the MTD for this compound is between 5,000 and 20,000 ppm in diet in male and female dogs. 

The LOAEL is 125 mg/kg/day, based on increased urinary volume, kidney weights, and 

osmolarity. The NOAEL is 6.25 mg/kg/day. 

Comments about Study and Endpoint: 

No dermal studies are available for rimsulfuron, therefore, the 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.

3.4.5 Inhalation Exposure (Short-, Intermediate-Term)

Study Selected: 90 Day Toxicity-Dog

MRID No. 41356322 

Dose and Endpoint for Risk Assessment: See above, under Dermal Exposure

Executive Summary: See above, under Dermal Exposure)

 

Comments about Study and Endpoint: 

In the absence of a route-specific inhalation toxicity study for rimsulfuron, HED relied on the 

oral toxicity study in dogs for inhalation risk assessment. The selected endpoint provides the 

most sensitive NOAEL available from an oral study of appropriate duration for short- and 

intermediate-term exposures. Since the endpoint was selected from an oral study, HED assumed 

equivalent toxicity via the inhalation and oral routes for the purpose of route-to-route 

extrapolation. 

3.4.6 Level of Concern for Margin of Exposure

The Level of Concern for Margins of Exposure (MOEs) is 100, based on the combined 

uncertainty factors of 10X for interspecies extrapolation and 10X for intraspecies variability. 
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The FQPA Safety Factor has been reduced to 1x and no additional safety factors have been

retained.

3.4.7 Recommendation for Aggregate Exposure Risk Assessments

When there are potential occupational and residential exposures to a pesticide, the risk 

assessment must address exposures from three major sources: oral, dermal and inhalation 

exposures, and determine whether the individual exposures can be combined if they have the 

same toxicological effects. For rimsulfuron, short-/intermediate-term dermal and inhalation 

exposure and risk are being assessed based on the same endpoint and dose from the oral study in 

the dog. Therefore, these routes of exposure can be combined. 

3.4.8 Classification of Carcinogenic Potential

The doses used in the two-year rat and 18-month mouse studies were adequate. No evidence of 

carcinogenicity was observed. Therefore, HED determined that rimsulfuron should be classified 

as “Not Likely to be Carcinogenic to Humans.” As such, there is no cancer risk associated with 

registered or proposed uses of rimsulfuron.

3.4.9 Summary of Toxicological Doses and Endpoints for Rimsulfuron for Use in Human 

Risk Assessments

A summary of the toxicological endpoints and doses chosen for the relevant exposure scenarios 

for human risk assessment is found in Table 3.4.9.

Table 3.4.9. Toxicological Doses and Endpoints for Rimsulfuron for Use in Human Health Risk Assessments.

Exposure

Scenario

Point of 

Departure

Uncertainty/F

QPA Safety 

Factors

RfD, PAD, Level of Concern for 

Risk Assessment

Study and Toxicological 

Effects

Acute Dietary

(females 13-49)

Acute Dietary

(general 

population)

No appropriate endpoint attributable to a single dose identified.

Chronic Dietary

(all populations)

 

NOAEL= 11.8 

mg/kg bw/day

UFA=10x

UFH=10x

FQPA SF=1x

Chronic RfD = chronic NOAEL

 Safety Factors

= 0.118 mg/kg bw/day

cPAD = Chronic RfD

 FQPA SF

= 0.118 mg/kg bw/day

Combined 

Chronic/CarcinogenicityRat

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 Use pattern does not indicate a need for this risk assessment.
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Table 3.4.9. Toxicological Doses and Endpoints for Rimsulfuron for Use in Human Health Risk Assessments.

Exposure

Scenario

Point of 

Departure

Uncertainty/F

QPA Safety 

Factors

RfD, PAD, Level of Concern for 

Risk Assessment

Study and Toxicological 

Effects

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

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).

4.0 Public Health and Pesticide Epidemiology Data

There are no new public health data or pesticide epidemiology data to report at this time.

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 goat, and laying hen. 

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. Based on the results of the studies, HED 
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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 

and grown to maturity. 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

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: Samples were analyzed for rimsulfuron using the LC/MS/MS 

method, DuPont-15033 (Revision 1), as described above and in D326655. 

The submitted LS/MS/MS methods (Method 15033 and 15027, Revision 1) are adequate for 

enforcing tolerances. No new DER was written for the submitted revised methods (MRIDs

48332001 and 48332002), as they have been reviewed in a previously submitted petition (DP# 

326655, D. Rate, 5/13/2007). The current submission incorporates the ILV comments as 

previously requested by HED and fulfills the conditional data requirement set in D326655. The 

methods do not require a PMV trial, and can be forwarded to FDA.

5.1.4 Magnitude in Plants
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DP# 386512, E. Holman, September 2011

The available caneberry and blueberry field trial data are acceptable and support the proposed 

use patterns for rimsulfuron (WDG) on these proposed commodities. An adequate number of 

tests were conducted on each crop in the appropriate geographical regions. 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.

It is noted that while all the blueberry trials included an adjuvant in the spray mixture (NIS or 

COC), none of the caneberry trials included adjuvants. Given that the blueberry trials, including 

adjuvant, yielded residues <0.01 ppm (LOQ), identical to the result of the caneberry trials 

without adjuvant, the impact of adjuvants is believed to be minimal. Therefore, while the 

proposed label does not include discussion of the use of adjuvants on the proposed commodities, 

HED does not believe that prohibition of the use of adjuvants on caneberry is necessary. The 

proposed use pattern and label is adequate and revisions are not required. 

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). A summary of the degradation profiles in various laboratory systems is included in 

Table 5.1.5.

Table 5.1.5. Transformation/degradation profiles of rimsulfuron in various systems.

Degradate

Name 

Max Degradate Concentration in % of applied and (Time in Days to Max Concentration; Does it 

Decline Y/N)

Hydrolysis @ 

pH7 Aerobic Soil Anaerobic Soil Other Studies

IN-70941 17%

(3 days; Y to 1%)

55%

(10 days; Y to 30%)

32%

(10 days; Y to 6%)

H2OPhotolysis: Similar to 

hydrolysis with reduction in 

transformation of IN-70941 into IN70942 and/or increase in the 

degradation of IN-70942. Plus 

enhanced formation of IN-J920 and 

IN-E9260

Aerobic Aquatic Data: May not 

represent the natural environment as 

the system was exposed to light

TFD (Terrestrial Field 

Dissipation) Data: None Identified 

possibly due to inappropriate 

LOD/LOQ (limits of 

detection/quantification)

IN-70942 84%

(30 days; N)

30%

(360 days; N)

56%

(360 days; N)

IN-E9290 10%

(30 days; N)

19%

(30 days; Y to 16%)

23%

(360 days; N)

IN-J290 7%

(14 days; Y to 6%)

3%

(30 days; Y to 1%)

8%

(28 days; Y to 6%)
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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. While the cleavage of the bridge to form the 

pyridinesulfonamide metabolite is expected, the contraction reaction is not. 

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. While the cleavage of the bridge to form the pyridinesulfonamide 

metabolite is expected, the contraction reaction is not. The major residue found in plants is the

parent compound, rimsulfuron. 

5.1.7 Pesticide Metabolites and Degradates of Concern

Table 5.1.7. Summary of Metabolites and Degradates to be Included in the Risk Assessment and Tolerance 

Expression.

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Plants Primary Crop rimsulfuron rimsulfuron

Rotational Crop rimsulfuron Not Applicable

Livestock Ruminant rimsulfuron Not Applicable

Poultry rimsulfuron Not Applicable

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

EFED previously assessed the drinking water residue profile for rimsulfuron (DP 358869 and 

358875). The maximum use rate of 0.0625 lb ai/A/season for citrus, pome and stone fruit that 

was previously assessed is equivalent to the proposed use rate on caneberry and blueberry. 

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: 
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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, and 

pistachios; 0.05 ppm in/on tomatoes, 0.09 ppm in/on almond hulls, and 0.1 ppm in/on field corn 

grain, forage, and stover. The recommended tolerances associated with the new uses of 

rimsulfuron on caneberry and bushberry is 0.01 ppm on all associated commodities. In addition, 

the dietary exposure assessment includes chicory (roots and tops), which also has a proposed 

tolerance of 0.01 ppm. The proposed use on chicory will be assessed separately under the 

forthcoming memo D391764. 

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. 

5.1.10 International Residue Limits

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

rimsulfuron. However, there is a Canadian MRL of 0.05 ppm for rimsulfuron residues on 

blueberry, based on their method LOQ of 0.05 ppm and no residues above LOQ being observed 

in their reviewed field trials. Given the availability of a more sensitive analytical method with an 

LOQ of 0.01 ppm, HED recommends proceeding with setting a tolerance for the bushberry crop 

group of 0.01 ppm, which includes the blueberry commodity. With PMRA having only a 

tolerance on blueberry of 0.05 ppm, if USEPA were to harmonize tolerances on this commodity, 

this would result in an inconsistency with the remaining commodities in the bushberry crop 

group. 
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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 + water) exposure estimates using the DEEM-FCIDTM 

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.” Therefore, there is no cancer risk

associated with existing or proposed uses. 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization
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There are currently no residential uses for rimsulfuron, therefore no non-occupational exposure 

is expected to result from the proposed and labeled uses.

6.1 Other (Spray Drift, etc.)

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 (a 

membership of US pesticide registrants), EPA Regional Offices, State Lead Agencies for 

pesticide regulation, and other parties to develop the best spray drift management practices. The 

Agency is now requiring interim mitigation measures for aerial applications that must be placed 

on product labels/labeling. The Agency has completed its evaluation of the new database 

submitted by the Spray Drift Task Force, 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, 

and risks associated with pesticide application. 

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 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 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 

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
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D394390, S. Oonnithan, November 9, 2011

9.1 Short-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 Matrix®SG Herbicide for ground boom applications 

- Applying the spray mixture by a ground boom sprayer 

- Mixing, loading and applying by a low-pressure handwand 

- Mixing, loading and applying by a back-pack sprayer 

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

boom or band sprayers. Spot applications may be made with backpack and low pressure hand 

wand 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, only one application on berries is allowed 

per year at the maximum rate of 0.063 lb ai/A, resulting in short-term handler exposures. 

However, HED typically assumes commercial applicators use rimsulfuron for longer durations 

(> 1 month), and therefore intermediate-term exposures were 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 

changes, etc. are considered. The proposed PPE includes long-sleeved shirt and long pants, 

shoes plus socks and chemical resistant gloves. 
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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 bush- and caneberries. 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 ≥ 370 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 Bush- and Caneberries.

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

0.063

80

227 8.96 0.01634 0.00065 0.01699 370

Applying with a ground boom sprayer 

(AHETF) 

SL,

Open cab 78.6 0.34 0.00566 0.00002 0.00568 1,100

Mixing/loading/applying with a backpack sprayer (OPHED) SL, 

Gloves 5

2,500 30 0.01125 0.00014 0.01139 550

Mixing/loading/applying with a lowpressure handwand sprayer (OPHED) 430 30 0.00194 0.00014 0.00207 3,000

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 (70 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 (70 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 Postapplication Exposure and Risk

Rimsulfuron is applied as a ground-directed pre- and postemergence spray to control weeds in 

bush- and cane berries. Common postapplication activities performed on commercially grown 

bush berries are pruning and hedging of vines, irrigation and scouting which have the potential 

for dermal exposure to workers performing such activities. But, the proposed label recommends 

use of a directed spray application adjusted to provide complete coverage of the weeds while 

minimizing the amount of spray contacting berry plant foliage. In addition, the label advises 

growers to time rimsulfuron application(s) to take advantage of normal rainfall patterns in order 

to optimizing herbicide performance. Both these application methods are expected to result in 

little or no dermal exposure to workers doing bushberry-related cultural practices following 

treatment, and therefore a postapplication exposure assessment was not conducted. In addition, 

dermal exposure for handlers applying Matrix® SG Herbicide on bush- and caneberries results in 

significantly higher exposures; thus, handler exposures would be protective of all potential 

postapplication exposure scenarios. 

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

assessment was not performed for use of rimsulfuron on bush- and caneberries, primarily 

because of the low vapor pressure (1.1 X 10-8torr at 25 °C), low application rate (0.063 lb ai/A)

and ground-directed method of application. However, there are multiple potential sources of 

postapplication 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, and 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 postapplication 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 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 occupational postapplication 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.
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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

As part of the new part 158 guidelines, the following studies are still needed to complete the 

toxicity database: acute and subchronic neurotoxicity, immunotoxicity and a 21/28 day dermal 

toxicity study. These data requirements were previously noted in the 2009 risk assessment 

(DP360852, D. Rate, 13/AUG/2009). Progress towards meeting these requirements is being 

made, including EPA receipt of the proposal for the rimsulfuron immunotoxicity testing 

regarding species and dose selection to fulfill the 870.7800 guideline study. This proposal has 

been reviewed by HED (D384959, J. Kidwell, 5/Jan/2011) and the registrant should incorporate 

these recommendations into their forthcoming immunotoxicity data submission. 

10.2 Residue Chemistry

None

10.3 Occupational and Residential Exposure

None.

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/2006

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

D394390, S. Oonnithan, Nov. 2011
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Appendix A: Toxicology Assessment

A.1 Toxicity Profiles

Table A.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 A.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 A.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.

LOAEL = 342.4 mg/kg/day) based on 
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Table A.1.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No./ Study 

Type

MRID No. (year)/ Classification /Doses Results

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, 

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.
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A.2 Rationale for Toxicology Data Requirements.

Table A.2.1. Guideline Number: 870.6200

Study Title: Acute & Subchronic Neurotoxicity

Rationale for Requiring the Data

The acute and subchronic neurotoxicity studies are a new data requirement under 40 CFR Part 158 

as a part of the data requirements for registration of a pesticide (food and non-food uses). 

The Neurotoxicity Test Guideline (OPPTS 870.6200) prescribes functional and structural 

neurotoxicity testing and is designed to evaluate the potential of a repeated chemical exposure to 

produce adverse effects on the nervous system. Although some information on neurotoxicity may 

be obtained from standard guideline toxicity study data, studies not specifically conducted to 

assess neurotoxic endpoints may be inadequate to characterize a pesticide’s potential 

neurotoxicity. While data on clinical signs of toxicity or histopathology in routine chronic or 

subchronic toxicity studies may offer useful information on potential neurotoxic effects, these 

endpoints alone may be insufficient to detect more subtle neurological effects. 

Practical Utility of the Data

How will the data be used?

Neurotoxicity studies provide critical scientific information needed to characterize potential 

hazard to the human population on the nervous system from pesticide exposure. Since 

epidemiologic data on the effects of chemical exposures on neurologic parameters are limited and 

may be inadequate to characterize a pesticide’s potential neurotoxicity in humans, animal studies 

are used as the most sensitive endpoint for risk assessment. These animal studies can be used to 

select endpoints and doses for use in risk assessment of all exposure scenarios and are considered 

a primary data source for reliable reference dose calculation.

How could the data impact the Agency's future decision-making? 

If the neurotoxicity studies show that the test material poses either a greater or a diminished risk 

than that given in the interim decision’s conclusion, the risk assessments for the test material may 

need to be revised to reflect the magnitude of potential risk derived from the new data.

If the Agency does not have these data, a 10X database uncertainty factor may be applied for

conducting a risk assessment from the available studies.

Table A.2.2. Guideline Number: 870.7800

Study Title: Immunotoxicity

Rationale for Requiring the Data

The immunotoxicity study is a new data requirement under 40 CFR Part 158 as a part of the data 

requirements for registration of a pesticide (food and non-food uses). 

The Immunotoxicity Test Guideline (OPPTS 870.7800) prescribes functional immunotoxicity 

testing and is designed to evaluate the potential of a repeated chemical exposure to produce 

adverse effects (i.e., suppression) on the immune system. Immunosuppression is a deficit in the 

ability of the immune system to respond to a challenge of bacterial or viral infections such as 

tuberculosis (TB), Severe Acquired Respiratory Syndrome (SARS), or neoplasia. Because the 

immune system is highly complex, studies not specifically conducted to assess immunotoxic 

endpoints are inadequate to characterize a pesticide’s potential immunotoxicity. While data from 
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hematology, lymphoid organ weights, and histopathology in routine chronic or subchronic toxicity 

studies may offer useful information on potential immunotoxic effects, these endpoints alone are 

insufficient to predict immunotoxicity. 

Practical Utility of the Data

How will the data be used?

Immunotoxicity studies provide critical scientific information needed to characterize potential 

hazard to the human population on the immune system from pesticide exposure. Since 

epidemiologic data on the effects of chemical exposures on immune parameters are limited and 

are inadequate to characterize a pesticide’s potential immunotoxicity in humans, animal studies 

are used as the most sensitive endpoint for risk assessment. These animal studies can be used to 

select endpoints and doses for use in risk assessment of all exposure scenarios and are considered 

a primary data source for reliable reference dose calculation. For example, animal studies have 

demonstrated that immunotoxicity in rodents is one of the more sensitive manifestations of TCDD 

(2,3,7,8-tetrachlorodibenzo-p-dioxin) among developmental, reproductive, and endocrinologic 

toxicities. Additionally, the EPA has established an oral reference dose (RfD) for tributyltin oxide 

(TBTO) based on observed immunotoxicity in animal studies (IRIS, 1997).

How could the data impact the Agency's future decision-making? 

If the immunotoxicity study shows that the test material poses either a greater or a diminished risk 

than that given in the interim decision’s conclusion, the risk assessments for the test material may 

need to be revised to reflect the magnitude of potential risk derived from the new data.

If the Agency does not have these data, a 10X database uncertainty factor may be applied for 

conducting a risk assessment from the available studies.

Guideline Number: 870.3250

Study Title: 21/28-Day Dermal Toxicity 

Rationale for Requiring the Data

The subchronic (21/28-day) dermal toxicity study is a new data requirement under 40 CFR Part 

158 as a part of the data requirements for registration of a pesticide for food use.

The dermal toxicity Test Guidelines (OPPTS.870.3250) is intended to evaluate the toxic effects 

associated with continuous or repeated exposures to a test substance for a period of 21/28-days. 

The Agency needs a 21/28-day dermal toxicity study for food use pesticides because a 

route-specific study eliminates the uncertainties associated with use of an oral study and 

dermal absorption factors for dermal risk assessments

Practical Utility of the Data

How will the data be used? 

A route specific (i.e., dermal) study will provide critical scientific information needed to 

characterize potential hazard to the human population exposed to the pesticide by the dermal 

route. This study will provide a dose and a toxicological endpoint of concern for quantification 

of risks for dermal exposures. This study would eliminate the uncertainties associated with the 

use of an oral study with a default (100% oral equivalent) dermal absorption factor. 

In many cases, toxicity observed via the dermal route will be different than toxicity observed 
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via oral exposure, due to absorption and distribution of the toxic agent after exposure or 

differences in metabolism (i.e., systemic versus local). This means that the route-to-route 

extrapolation (i.e., use of an oral dose/endpoint) in risk assessment could result in under or over 

estimation of risks from the dermal route. 

How could the data impact the Agency’s future decision-making?

If the dermal toxicity study indicates that the test material poses either a greater or lesser risk 

than that calculated using an oral dose, (as used in the interim decision), the risk assessment 

would be revised to reflect the magnitude of potential risk derived from the new data. Also, the 

requested data would allow the Agency to determine if the risks were over-estimated or underestimated. If the risks were under-estimated, additional risk mitigation measures could be 

required. If the risks were over-estimated, risk mitigation measures could be reduced.
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Appendix B: Tolerance Setting

Table B.1. Tolerance Summary for Rimsulfuron.

Commodity Proposed Tolerance 

(ppm)

Recommended 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

Caneberry, 

subgroup 13-07A 0.01 0.01

Bushberry, 

subgroup 13-07B 0.01 0.01

Set at 0.01 ppm, a value that is not 

harmonized with the MRL in Canada

of 0.05 ppm (set on blueberry).

Appendix C: Review of Human Research

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

intentionally exposed to a pesticide or other chemical. These studies, which comprise the 

Occupational Pesticide Handlers Exposure Database (OPHED) 

(http://www.epa.gov/pesticides/science/handler-exposure-data.html and

http://www.epa.gov/pesticides/science/post-app-exposure-data.html) have been determined to 

require a review of their ethical conduct, have received that review, and have been determined to 

be ethically conducted.