Page 2 of 18

The chlorsulfuron risk assessment incorporates several conservative assumptions and is 

considered to be a very conservative estimate of risk to chlorsulfuron. The human health 

risks are low due to its low toxicity (Toxicity Category III and IV), the minimal dietary 

and occupational/residential risk, and its “no evidence of carcinogenicity” classification.

The toxicology database for chlorsulfuron is considered substantially complete for the 

purposes of registration review risk assessment. An immunotoxicity study is the only 

remaining data requirement. 

The existing residue chemistry database for chlorsulfuron is adequate for risk assessment 

purposes. The qualitative nature of the residues of chlorsulfuron in plants and animals 

has been adequately identified/characterized and adequate enforcement analytical 

methods are available. The current tolerance expression as listed in the 40 CFR§180.405

has not been updated to reflect current HED policies and thus may need to be revised 

during the registration review process.

The dietary exposure database is also adequate to support the existing registrations. 

Acute and cancer dietary risk assessments are not required for chlorsulfuron. In the last 

dietary assessment, the chronic dietary exposure for food only was not greater than 8% of 

the cPAD for all population subgroups. Risks from potential exposure to chlorsulfuron in 

drinking water from all sources were evaluated by comparing modeled surface and 

ground water estimates against calculated drinking water levels of comparison 

(DWLOCs). This assessment indicated that the estimated drinking water concentration 

(EDWC) estimates for chlorsulfuron residues in surface and ground water did not exceed 

the Agency’s estimated chronic DWLOC value. New chronic dietary exposure and risk 

assessments may be needed during registration review, which incorporate current 

consumption information, updated residue values and percent crop treated information 

while directly incorporating drinking water values into the assessment. Further, an acute 

dietary assessment may need to be completed if new toxicity data are identified that

indicate the need for an acute dietary risk assessment.

The residential exposure database is adequate to support the registration review process 

for chlorsulfuron. In accordance with the updated Part 158 data requirements (2007), a 

Turf Transferrable Residue (TTR) study is required for all occupational (e.g., sod farms, 

golf courses, parks, and recreational areas) or residential turf uses. Based on HED policy, 

a TTR study is not required for chlorsulfuron at this time. The requirement of a TTR 

study may need to be reconsidered if application rates, use patterns, or points of departure 

change. The chlorsulfuron residential exposure risk assessment should be considered 

conservative because of the low use rates, minimal re-applications (60 day interval) and 

high end values from the Residential Standard Operating Procedures (SOPs). HED 

determined that the margin of exposure (MOEs) were not of concern to adult residential 

handlers (MOEs ranged from 8,800 to 190,000) or residential post-application to adults 

and toddlers (MOEs ranged from 770 to 400,000). 

Based on the updated 2012 Residential SOPs, the Agency may reevaluate the residential 

handler and post-application exposures from the uses of chlorsulfuron. Therefore, 

updated aggregate exposure and risk assessments may also be required under registration 

review based on the need to combine exposure estimates from residential uses with 

dietary exposure estimates.
Page 3 of 18

As noted above in the dietary section, the 2002 risk assessment did not directly 

incorporate drinking water into the dietary assessment and thus a new chronic dietary 

assessment may be required during registration review. As a result, during registration 

review, new short-term, intermediate-term, and chronic aggregate risk assessments may

required.

The occupational exposure database is adequate to support the registration review process 

for chlorsulfuron. In accordance with the updated Part 158 data requirements (2007), one 

or more Dislodgeable Foliar Residue (DFR) studies are required when a pesticide has 

residential or occupational uses that could result in post-application dermal exposure. 

Based on HED policy, a DFR study is not required for chlorsulfuron at this time. The 

requirement of a DFR study may need to be reconsidered if application rates, use 

patterns, or points of departure change. In the 2002 exposure assessments, all of the noncancer occupational handler risk estimates were below the Agency’s level of concern. 

No new occupational handler or post-application worker studies are needed at this time. 

Revised occupational handler assessments would be based upon revisions to the 

Agency’s scenario-specific surrogate handler exposure data 

(http://www.epa.gov/pesticides/science/handler-exposure-table.pdf). 

Introduction

Chlorsulfuron is a systemic herbicide for use on barley, oats, wheat, fallow fields, and 

ornamental turf to control grasses and broadleaf weeds. HED has reviewed the most 

recent exposure and risk assessments for chlorsulfuron, as well as toxicity data, exposure 

and usage databases, and the latest Agency science policy and risk assessment 

methodologies to determine if sufficient data are available and if updates are needed to 

support registration review. Additionally, the team conducted a screening-level literature 

search for any information that would aid in assessing human health risks to 

chlorsulfuron.

Chemical Identity

Chlorsulfuron 2-chloro-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)amino 

carbonyl]benezenesulfonamide is a systemic herbicide that is currently registered for use 

on barley, oats, wheat, fallow fields, and ornamental turf to control grasses and broadleaf 

weeds. The chemical structure and nomenclature of chlorsulfuron and the 

physicochemical properties of the technical grade of chlorsulfuron are presented in 

Tables 1 and 2.

Hazard Identification/Toxicology

The toxicology database for chlorsulfuron is nearly complete at the present time with the 

exception of an immunotoxicity study (Table 3). In 2002, the HIARC had identified the 

21-day dermal toxicity and subchronic inhalation studies as data gaps for chlorsulfuron 

(TXR# 0050920, 2002). In addition, based on the current 40 CFR Part 158 Toxicology 

Data Requirements, the immunotoxicity, acute and subchronic neurotoxicity studies are 

required for chlorsulfuron. In 2012, the Hazard and Science Policy Council (HASPOC), 

based on a WOE approach and considering all of the available chlorsulfuron hazard and 
Page 4 of 18

exposure information, recommended that the 21-day dermal toxicity, inhalation toxicity,

and neurotoxicity battery studies not be required at this time (TXR# 0056439, 2012). 

However, an immunotoxicity study is required to support the registered uses of 

chlorsulfuron.

Chlorsulfuron has low acute toxicity by the oral, dermal, or inhalation route of exposure. 

It is not an eye or skin irritant, and is not a skin sensitizer. There is no evidence that 

chlorsulfuron is neurotoxic, teratogenic, reproductive, carcinogenic, mutagenic or 

clastogenic. The most prevalent effect observed across studies was on decreased body 

weight. For endpoint selection, there is no appropriate toxicity endpoint available to 

quantitate risk from a single-dose administration of chlorsulfuron. Consequently, there is

no acute reference dose (aRfD). The chronic reference dose (cRfD) is based on decreased 

body weights in a chronic/carcinogenicity study in rats. The short- and intermediate-term

incidental oral endpoints as well as the short- and intermediate term dermal and inhalation

endpoints are based upon decreases in maternal body weight and body weight gain seen in

a rabbit developmental toxicity study. The chronic endpoints for oral, dermal, and 

inhalation routes of exposure are based upon decreased body weight observed in male rats

in a chronic/carcinogenicity study. Chlorsulfuron is classified as "not likely to be 

carcinogenic to humans" based upon lack of evidence of carcinogenicity in rats and mice. 

Therefore, a cancer risk assessment is not required. Since no dermal absorption data are

available, toxicity by the dermal route was considered to be equivalent to toxicity by the

oral route of exposure, a default value of 100% dermal-absorption (relative to oral

absorption) was used. 

There is no evidence for increased quantitative or qualitative susceptibility of the young 

following in utero (rats and rabbits) and pre-and post-natal exposure (rats) to 

chlorsulfuron. In 2002, the FQPA Safety Factor Committee (SFC) evaluated the hazard

and exposure data for chlorsulfuron and recommended that the FQPA safety factor be 

removed (1x) in assessing the potential risk posed by this chemical. In addition, the

FQPA SFC determined that a 3x database uncertainty factor should be applied to address 

data deficiencies of a reproduction study. Subsequently, a two-generation reproduction 

study in rats (2005) was submitted which did not show any adverse effects on 

reproduction or toxicity to the offspring. The Points of Departure and the FQPA factor 

will be re-evaluated during registration review in accordance with current policy and 

submission of the outstanding data.

Chlorsulfuron is rapidly absorbed, metabolized, and eliminated in rats following oral 

administration. There is no remarkable sex-, dose-, or treatment-regiment-related 

difference in the absorption, distribution, and excretion of chlorsulfuron in rats. The 

major routes of elimination are via the urine (58-72% of the dose) and feces (20-35%). 

Negligible amounts (<0.08%) of radioactivity are found in the expired air as carbon 

dioxide. Small amounts of radioactivity were found in the tissues 3 days after dosing, 

with the highest concentrations being observed in the liver and whole blood in both 

sexes.

The Points of Departures and toxicological endpoints of concern for the overall risk 

assessment (dietary and occupational) are presented in Table 4. 
Page 5 of 18

Endocrine Disruption

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

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

subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, 

developmental, reproductive, and general or systemic toxicity. These studies include 

endpoints which may be susceptible to endocrine influence, including effects on 

endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, 

fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological 

hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, 

developmental and reproductive effects in different taxonomic groups. As part of its 

reregistration decision for chlorsulfuron, EPA reviewed these data and selected the most 

sensitive endpoints for relevant risk assessment scenarios from the existing hazard 

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

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

EPA has developed the EDSP to determine whether certain substances (including 

pesticide active and other ingredients) may have an effect in humans or wildlife similar to 

an effect produced by a “naturally occurring estrogen, or other such endocrine effects as 

the Administrator may designate.” The EDSP employs a two-tiered approach to making 

the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays 

to identify the potential of a chemical substance to interact with the estrogen, androgen, 

or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening 

and are found to have the potential to interact with E, A, or T hormonal systems will 

proceed to the next stage of the EDSP where EPA will determine which, if any, of the 

Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to 

identify any adverse endocrine-related effects caused by the substance, and establish a 

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

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

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

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

Chlorsulfuron is not among the group of 58 pesticide active ingredients on the initial list 

to be screened under the EDSP. Accordingly, as part of registration review, EPA will 

issue future EDSP orders/data call-ins, requiring the submission of EDSP screening 

assays for chlorsulfuron. For further information on the status of the EDSP, the policies 

and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 

screening battery, please visit our website: http://www.epa.gov/endo/.

Conclusions for Hazard Identification/Toxicology

The toxicology database for chlorsulfuron is nearly complete at the present time with the 

exception of an immunotoxicity study. Upon receipt of the required toxicity study, HED 

may re-evaluate the points of departure and uncertainty factors for the dietary, residential

and occupational exposure assessments. 

Residue Chemistry
Page 6 of 18

The existing residue chemistry database for chlorsulfuron is adequate for risk assessment 

purposes. No additional data are required at this time. The qualitative nature of the 

residues of chlorsulfuron in plants and animals has been adequately identified, 

characterized and is understood.

The HED Metabolism Assessment Review Committee (MARC) reviewed the 

chlorsulfuron toxicology and metabolism data (D213534, 4/4/95 and 7/18/95) and 

recommended that the tolerance and risk expression for plant and livestock should 

include parent only. The Agency has determined that tolerances for chlorsulfuron 

residues in eggs and poultry tissue are not required based on the results of the respective 

poultry metabolism and feeding studies.

Methods are available for the enforcement of chlorsulfuron tolerances in/on plant and 

animal commodities. An analytical method (AMR 3822-96) is adequate for data 

collection and enforcement for chlorsulfuron residues in/on the plant commodities wheat, 

barley, oats (grain, forage and straw) and grasses (forage and hay). PAM Vol. II lists 

Methods I and II, HPLC methods with photoconductivity detection (PCD), for the 

determination of chlorsulfuron residues in plants and livestock commodities and milk.

The confined accumulation in rotational crop studies indicated that limited field studies 

are not required. No tolerances are required for rotational crops, since product labels 

specify a plant-back interval of 4 months which is currently on the label.

Conclusions for Residue Chemistry

The database for chlorsulfuron is considered adequate for risk assessment and tolerance 

assessment. No new residue chemistry data requirements have been identified for 

chlorsulfuron to support registration review.

Dietary Exposure and Risks

An unrefined (tolerance level residues and 100% crop treated) chronic dietary risk 

assessment was completed in 2002 using the Dietary Exposure Evaluation Model 

(DEEM-FCIDTM) and USDA 1989-92 CSFII food consumption survey (F. Fort, 

D283507, 07/18/02).

Acute

Acute doses and endpoints were not selected for the general U.S. population (including 

infants and children) or the females 13-50 yrs old population subgroup for chlorsulfuron; 

therefore, an acute dietary exposure analysis was not performed.

Chronic

Chronic dietary risk (food only) estimates associated with the use of chlorsulfuron did not 

exceed the Agency’s level of concern for any population subgroup, including the most 

highly exposed subgroup children 1-6 yrs (8% of the chronic population adjusted dose). 

The 2002 dietary exposure assessment was the first dietary assessment that has been 

conducted for chlorsulfuron.
Page 7 of 18

Drinking Water

A Tier 1 (FIRST-FQPA Index Reservoir Screening Tool) screening level drinking water 

assessment was conducted to estimate pre-treatment surface water concentrations of total 

chlorsulfuron residues (both parent and degradation products) resulting from two 

applications, at 60 day intervals, of the maximum use rate. The estimate of 41.3 ppb for 

chronic (average annual) exposure was selected. The most recent assessment did not 

directly incorporate drinking water residues into the dietary assessment. The assessment 

was conducted using the DWLOC (drinking water level of concern) approach. 

Conclusions 

The dietary exposure database is adequate to support the existing registration. However, 

during registration review, a new drinking water assessment may be needed to 

incorporate the use of the most current drinking water models. The information available 

indicates that we may need to revisit the residues of concern decision to discuss the 

degradates/metabolites in drinking water The revised assessment should include updated 

consumption information, any changes in the toxicology endpoints, and utilize the latest 

version of DEEM-FCID.

Residential Exposure and Risks

Chlorsulfuron is registered for use on residential lawns, recreational areas (i.e., parks and 

sports fields), and on golf courses. Due to this use profile, adult residential homeowners 

may experience exposure to chlorsulfuron during application of the chemical (i.e., 

residential handler exposures). Adults and children may experience exposure to 

chlorsulfuron when contacting previously treated areas (i.e., residential post-application 

exposure).

Since the 2002 risk assessment, the Health Effects Division’s 2012 Standard Operating 

Procedures for Residential Pesticide Exposure Assessment were updated. 

Residential Handlers

In 2002, HED conducted an occupational and residential exposure assessment based on 

the treatment to turf. HED determined that the MOEs (ranged from 8,800 to 190,000) 

were not of concern to adult residential handlers (i.e., MOEs ≥100) (F. Fort, 7/18/02). 

Residential handler exposures were estimated using the standard values and assumptions 

from the Residential Exposure Assessment Standard Operating Procedures (September 

1999). 

 

For residential handlers, the major exposure scenarios identified and assessed previously 

include:

1) Mixer/loader/applicator: low pressure handwand,

2) Mixer/loader/applicator: backpack sprayer.

Residential Post-Application
Page 8 of 18

In 2002, HED conducted an occupational and residential post-application exposure 

assessment based on the treatment to turf. HED determined that the MOEs (ranged from 

770 to 400,000) were not of concern for residential post-application for adults and 

toddlers (i.e., MOEs ≥100) (F. Fort, 7/18/02). 

For residential post-application, the major exposure scenarios identified and assessed 

previously include:

1) Physical activities on turf: adults (dermal) and children (dermal and incidental 

oral).

Conclusions for Residential Exposure and Risks

The residential exposure database is adequate to support the registration review process 

for chlorsulfuron. In accordance with the updated Part 158 data requirements (2007), a 

TTR study is required for all occupational (e.g., sod farms, golf courses, parks, and 

recreational areas) or residential turf uses. As part of the recent revision to the Health 

Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide 

Exposure Assessment, HED analyzed all available data and selected new liquid and 

granular default values for the fraction of the application rate available for transfer after a 

turf application (FAR). These defaults are 1% for formulations applied as liquids (i.e., 

emulsifiable concentrates, liquids, wettable powders, dry flowables, etc.) and 0.2% for 

granular formulations. Of the available TTR studies submitted to the Agency, the 

maximum FAR value seen using a liquid product was 6.1% or 6.1 times higher than the 

default residue transfer value. The maximum FAR value seen in a TTR study using a 

granular product was 0.69% or 3.5X the default residue transfer value. Therefore, for 

both liquid and granular formulations, a calculated MOE of approximately 10 times 

higher than the level of concern (e.g., an MOE > 1,000 if the LOC = 100) using the 

default residue transfer values would provide an adequate margin of safety for any 

potentially higher residues seen in a chemical-specific TTR study (Guidance for 

Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue 

(DFR) Studies. 6/7/2012, Exposure Science Advisory Council). For chlorsulfuron, a

TTR study is not required at this time since the dermal and/or hand-to-mouth MOE is 

greater than 1,000 based on default values for the fraction of application rate available for 

transfer after a turf application. The requirement of a TTR study may need to be 

reconsidered if application rates, use patterns, or points of departure change. An updated 

residential exposure assessment may be required under registration review based upon 

revisions to HED’s 2012 Residential SOPs. An updated assessment may also be required 

if new data are identified which impact exposure estimates, new toxicological points of 

departure, or revisions to exposure policies and procedures are made.

Aggregate Exposure and Risk Assessment

The most recent aggregate assessment was completed in 2002 (F. Fort, 7/18/02). 

Aggregate exposure risk assessments were assessed for the following scenarios: shortterm (food + drinking water + residential) and chronic aggregate exposure (food + 

drinking water). An acute aggregate risk assessment was not performed because no acute 

endpoint was identified to determine the aRfD for the general population or any 

population subgroup. Intermediate- and long-term aggregate-risk assessments were not 
Page 9 of 18

performed because there are no registered or proposed uses of chlorsulfuron that result in 

intermediate- or long-term residential exposures. An aggregate cancer risk assessment 

was not performed because chlorsulfuron is classified as “not likely to be carcinogenic to 

humans”.

The total short-term food and residential aggregated MOEs are ≥ 722. As this MOE is 

greater than 100, the short-term aggregate risks do not exceed HED’s Level of Concern 

(LOC). Since there are no registered/proposed uses that result in chronic residential 

exposure, the chronic aggregate exposure assessment consists of exposure from food and 

drinking water only. The chronic dietary exposure for food alone was not greater than 

8% of the cPAD for all population groups and, therefore, do not exceed HED’s LOC.

Conclusions for Aggregate Exposure and Risk Assessment

Updated aggregate exposure and risk assessments may be required under registration 

review based on the need for directly incorporating drinking water estimates into the 

dietary assessment. These revised aggregate exposure and risk assessments may also 

reflect any toxicological endpoint changes or other new data are received by the Agency 

that may impact exposure estimates.

Occupational Exposure and Risks

Chlorsulfuron 2-chloro-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)amino 

carbonyl]benezenesulfonamide, a systemic herbicide is currently registered for use on 

barley, oats, wheat, fallow fields, and ornamental turf to control grasses and broadleaf 

weeds. It is applied by groundboom sprayer, handheld sprayers, and aerial application.

Occupational Handlers

In 2002, HED conducted an occupational exposure assessment for pasture and rangeland 

grasses. The proposed rate of 1 oz ai/A/season on rangeland and pasture grasses was 

within rates currently registered on cereal grains (wheat, barley, and fallow fields). HED

determined that the MOEs (ranged from 1,000 to 56,000) were not of concern to 

mixers/loaders and applicators (i.e., MOEs ≥100) (F. Fort, 7/18/02).

The major exposure scenarios identified and assessed previously include:

Mixer/Loaders

1) Mixing/loading dry flowable for aerial application (wheat, high acreage),

2) Mixing/loading dry flowable for aerial application (cereal grains only, 

low acreage), 

3) Mixing/loading dry flowable for groundboom application (cereal grains),

4) Mixing/loading dry flowable for groundboom application (grass areas),

5) Mixing/loading dry flowable for high pressure handwand application 

(grass areas).

Applicators
Page 10 of 18

1) Applying sprays by aerial application (wheat),

2) Applying sprays by aerial application (cereal grains only),

3) Applying sprays by groundboom application (cereal grains only),

4) Applying sprays by groundboom application (grass areas),

5) Applying sprays by high pressure handwand (cereal grains only).

Flaggers

1) Flaggers for aerial application (cereal grains only).

These scenarios were assessed using the maximum application rate from the proposed 

label, exposure data from Pesticide Handlers Exposure Database (PHED) Version 1.1, 

(1998) and assumptions for area treated from Science Advisory Council for Exposure 

(ExpoSAC) Policy #9.1 (September 25, 2001).

Occupational Post-application

An occupational post-application exposure or risk estimate was not performed for 

chlorsulfuron. Occupational post-application exposure is not expected due to the early 

season (applied at germination or actively growing) and the use pattern on crops with 

minimal worker activity after application of chlorsulfuron(F. Fort, 7/18/02). 

Since chlorsulfuron is classified as Toxicity Category III for acute dermal and Toxicity 

Category IV for acute oral, and eye irritation, the Worker Protection Standard (WPS) 

Restricted-Entry Interval (REI) is 12 hours. However, there are several labels where the 

REI is 4 hours so this information should be considered and resolved during the 

registration review process.

Conclusions for Occupational Exposure and Risks

The occupational exposure database is adequate to support the registration review process 

for chlorsulfuron. In accordance with the updated Part 158 data requirements (2007), one 

or more DFR studies are required when a pesticide has residential or occupational uses 

that could result in post-application dermal exposure. As part of the recent revision to the 

Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide 

Exposure Assessment, HED analyzed a number of DFR studies and selected a new 

default value for the fraction of the application rate available to be dislodged after a foliar 

application (FAR). This default value is 25% and is based on an analysis of 19 DFR 

studies where the FAR value ranged from 2% to 89%. This value is recommended for use 

in both residential and occupational postapplication assessments. Of the analyzed DFR

studies, the maximum FAR value seen was 89% or 3.6 times higher than the default 

residue transfer value. Therefore, the HED has decided that a calculated MOE of 

approximately 4 times higher than the level of concern (e.g., an MOE > 400 if the LOC = 

100) using the default dislodged residue values would provide an adequate margin of 

safety for any potentially higher residues seen in a chemical-specific DFR study 

(Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable 

Foliar Residue (DFR) Studies. 6/7/2012, Exposure Science Advisory Council). For 

chlorsulfuron, a DFR study is not required at this time since the dermal MOE is greater 

than 400 based on default values for the fraction of application rate available for transfer 
Page 11 of 18

after a foliar application. The requirement of a DFR study may need to be reconsidered if 

application rates, use patterns, or points of departure change. Updated occupational 

handler exposure assessments may be required under registration review based upon 

revisions to the Agency’s scenario-specific surrogate handler exposure data 

(http://www.epa.gov/pesticides/science/handler-exposure-table.pdf). An occupational 

post-application assessment may also be required under registration review if 

toxicological endpoints change or other new data are received by the Agency that impact 

exposure estimates.

Human Studies

Past chlorsulfuron risk assessments rely in part on data from studies in which adult 

human subjects were intentionally exposed to a pesticide or other chemical. Studies such 

as the Pesticide Handlers Exposure Database, Outdoor Residential Exposure Task Force, 

and Agricultural Handler Exposure Task Force have been reviewed by the Agency and 

found on the basis of available evidence to have been neither fundamentally unethical nor 

significantly deficient relative to standards of ethical research conduct prevailing when 

they were conducted. There is no barrier in EPA's "Protection of Human Subjects" 

regulation to reliance on these studies.

Public Health and Pesticide Epidemiology Data

An updated review of chlorsulfuron incident reports was recently prepared by HED (S. 

Recore, D403831, 7/31/2012). For this evaluation, the OPP Incident Data System (IDS) 

was consulted for pesticide incident data on the active ingredient chlorsulfuron.

The IDS includes reports of alleged human health incidents from various sources, 

including mandatory Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) 

Section 6 (a) (2) reports from registrants, other federal and state health and environmental 

agencies and individual consumers. IDS contains reports from across the U.S. and most 

incidents have all relevant product information recorded. Reports submitted to the IDS 

represent anecdotal cases or allegations only, unless otherwise stated. IDS records 

incidents resulting in higher severity outcomes in more detail, in a module called the 

Main IDS module. This system stores incident data for death, major and moderate 

incidents, and it includes more details about the location, date and nature of the incident.

For the Main IDS, from January 1, 2007 to June 13, 2012 there are no cases reported that 

involves the active ingredient chlorsulfuron. In the Aggregate IDS, from January 1, 2007 

to June 13, 2012, there are 7 incidents reported for chlorsulfuron. Because it falls within 

the categories reported as counts (which includes minor, unknown or no effects), there is 

no unique report that provides details about the incident and single chemical incidents are 

not distinguished from multiple chemical incidents; however, a high frequency of 

incidents indicates there is a high potential for exposure and vice versa. For 

chlorsulfuron, there appears to be a low potential for exposure. Chlorsulfuron is not 

included in the Agricultural Health Study (AHS), and therefore, does not provide 

information for this report. 

Based on the low frequency and severity of incident cases, there does not appear to be a 

concern at this time that would warrant further investigation. The Agency may continue 
Page 12 of 18

to monitor the incident information and if a concern is triggered, additional analysis may

be included during registration review.

Tolerance Assessment and International Harmonization

Tolerances are established under 40 CFR §180.405 for residues of the herbicide 

chlorsulfuron parent and its metabolite, in or on a variety of food and feed crops. There 

are currently no established or proposed Codex or Mexican MRLs for chlorsulfuron. 

Canada MRLs are harmonized with the established US tolerances for oat, wheat, and 

barley grain (see Table 5).

The current tolerance expression as listed in the 40 CFR §180.405 has not been updated 

to reflect current HED policies. The tolerance expression may need to be revised during 

the registration review process. The revised tolerance expression should be as follows: 

Tolerances are established under 40 CFR §180.405 for residues of the herbicide 

chlorsulfuron, including its metabolites and degradates, in or on the following 

commodities. Compliance with the tolerance levels specified is to be determined by 

measuring only parent chlorsulfuron, 2-chloro-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-

yl)aminocarbonyl]benzenesulfonamide in or on the commodity.

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 LowIncome Populations," 

http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf. The Office 

of Pesticide Programs (OPP) typically considers the highest potential exposures from the 

legal use of a pesticide when conducting human health risk assessments, including, but 

not limited to, people who obtain drinking water from sources near agricultural areas, the 

variability of diets within the U.S., and people who may be exposed when harvesting 

crops. Should these high exposures indicate potential risks of concern, OPP may further 

refine the risk assessments to ensure that the risk estimates are based on the best available 

information.

Cumulative Risk Assessment

At this time, EPA does not have available data to determine whether chlorsulfuron has a 

common mechanism of toxicity with other substances. EPA has not made a common 

mechanism of toxicity finding as to chlorsulfuron and any other substances, and 

chlorsulfuron does not appear to produce a toxic metabolite produced by other substances 

which have tolerances in the U.S. Therefore, EPA has not assumed that chlorsulfuron 

has a common mechanism of toxicity with other substances.

Data Requirements
Page 13 of 18

HED does not anticipate that additional residue chemistry, toxicology or 

occupational/residential exposure data may be required for the chlorsulfuron registration 

review process, with the exception of the following studies listed below:

Immunotoxicity Study (OPPTS 870.7800) 
Page 14 of 18

TABLE 1. Chlorsulfuron Nomenclature

Compound Chemical Structure

Common name Chlorsulfuron

IUPAC name 2-chloro-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbonyl]benzenesulfo

namide

CAS name Chlorsulfuron

CAS # 64902-72-3

TABLE 2. Physicochemical Properties of the Technical Grade Chlorsulfuron

Parameter Value Reference

Melting point/range 170-173 D182353, A. Aikens, 

12/4/1992

pH 3.8

Density 1.48 g/cm3

Water solubility ( 25 C) 3.18 g/100 grams water

Solvent solubility (mg/L at __ C) 3.7 g/100 ml acetone

2.1 g/100 ml acetonitrile

1.5 g/100 ml methanol

Vapor pressure at 25 C 2.3 x 10-11 mmHg

Dissociation constant (pKa) 3.4

Octanol/water partition coefficient 

Log(KOW)

2.13 at pH 5

UV/visible absorption spectrum Not available
Page 15 of 18

Table 3. Chlorsulfuron Toxicology Data Requirements

Test Technical

Required Satisfied

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

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

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

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

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

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

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

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

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

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

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

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

yes

yes

yes

no

no

yes

yes

yes1

-

-

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

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

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

yes

yes

yes

yes

yes

yes

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

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

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

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

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

yes

no

yes

yes

yes

yes

-

yes

yes

yes

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

870.5xxx Mutagenicity—Structural Chromosomal Aberrations...

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

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

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

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

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

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

no

no

yes

yes

no

-

-

yes1

yes1

-

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

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

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

yes

no

yes

yes

-

no

1HASPOC recommends that the 21-day dermal, subchronic inhalation toxicity, and neurotoxicity battery studies are not required at 

this time.
Page 16 of 18

Table 4. Toxicological Doses and Endpoint for Chlorsulfuron Human Health Risk Assessment

Exposure/Scenario Point of 

Departure

Uncertainty/FQPA 

Safety Factors

RfD, PAD, Level of Concern 

for Risk Assessment

Study and Toxicological 

Effects

Acute Dietary

(All populations)

No appropriate endpoint was identified including developmental toxicity studies in rats and rabbits.

Chronic Dietary (all 

populations) 

NOAEL = 5

mg/kg/day

UFA = 10X 

UFH = 10X 

UFDB = 3X

FQPA SF = 1X

Chronic RfD 

= 0.02 mg/kg/day

cPAD = Chronic RfD

 FQPA SF

= 0.02 mg/kg/day

Chronic toxicity/ 

carcinogenicity study in rats

LOAEL = 25 mg/kg based on 

decreased body weights in 

males.

Incidental Oral Exposure

Oral

Short- and 

Intermediate – Term

NOAEL=75 

mg/kg/day

UFA = 10X 

UFH = 10X 

UFDB = 3X

FQPA SF = 1X

LOC for MOE= 300 Developmental toxicity study in

rabbits

LOAEL=200 mg/kg/day based 

on decreased body weight gains.

Dermal Exposure

Dermal 

Short- Term (1- 30 

days) 

Intermediate – Term

(1-6 months)

NOAEL = 75 

mg/kg/day

UFA = 10X 

UFH = 10X 

UFDB = 3X

FQPA SF = 1X

Dermal Absorption

= 100%

Residential LOC for 

MOE= 300

Occupational LOC for 

MOE= 100

Developmental toxicity study in

rabbits

LOAEL=200 mg/kg/day based 

on decreased body weight gains.

Dermal

Long – Term

(>6 months)

NOAEL = 5 

mg/kg/day

UFA = 10X 

UFH = 10X 

UFDB = 3X

FQPA SF = 1X

Dermal Absorption

= 100%

Residential LOC for 

MOE= 300

Occupational LOC for 

MOE= 100

Chronic toxicity/ 

carcinogenicity study in rats

LOAEL = 25 mg/kg based on 

decreased body weights in 

males.

Inhalation Exposure

Inhalation 

Short- Term (1- 30 

days) 

Intermediate – Term

(1-6 months)

NOAEL = 75 

mg/kg/day

UFA = 10X 

UFH = 10X 

UFDB = 3X

FQPA SF = 1X

Inhalation Absorption 

= 100%

Residential LOC for 

MOE= 300

Occupational LOC for 

MOE= 100

Developmental toxicity study in

rabbits

LOAEL=200 mg/kg/day based 

on decreased body weight gains.

Inhalation

Long – Term

(>6 months)

NOAEL = 5 

mg/kg/day

UFA = 10X 

UFH = 10X 

UFDB = 3X

FQPA SF = 1X

Inhalation Absorption 

= 100%

Residential LOC for 

MOE= 300

Occupational LOC for 

MOE= 100

Chronic toxicity/ 

carcinogenicity study in rats

LOAEL = 25 mg/kg based on 

decreased body weights in 

males.

Cancer

Cancer (oral, dermal, 

inhalation) Classification: not likely to be carcinogenic to humans

UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed 

adverse effect level, PAD = population adjusted dose (a = acute, c = chronic), RfD = reference dose, MOE = margin of exposure, LOC 

= level of concern, NA = Not Applicable. UFA= extrapolation from animal to human (interspecies), UFH = potential variation in 

sensitivity among members of the human population (intraspecies). UFDB = to account for the absence of key data (i.e., lack of a 

critical study). 

Note: The FQPA database uncertainty factor (UFDB) may be re-evaluated during registration review based on the results of all 

available data.

International Residue Limits 

Table 5. Summary of US and International Tolerances and Maximum Residue Limits for 

Chlorsulfuron 

Residue Definition:

US Canada Mexico1 Codex2
Page 17 of 18

Table 5. Summary of US and International Tolerances and Maximum Residue Limits for 

Chlorsulfuron 

Residue Definition:

US Canada Mexico1 Codex2

US [40 CFR §180.405(a)(1)]

Plants: Tolerances are established 

for the combined residues of 

chlorsulfuron (2-chloro- N- [(4-

methoxy-6-methyl-1,3,5-triazin-2-

yl)aminocarbonyl]benzenesulfonam

ide) and its metabolite, 2-chloro-5-

hydroxy- N- [(4-methoxy-6-methyl1,3,5-triazin-2-yl)aminocarbonyl] 

benzenesulfonamide 

benzenesulfonamide, 2-chloro-N-[[(4-

methoxy-6-methyl-1,3,5-triazin-2-

yl)amino]carbonyl]-, including the 

metabolite benzenesulfonamide, 2-

chloro-5-hydroxy-N-[[(4-methoxy-6-

methyl-1,3,5-triazin-2-

yl)amino]carbonyl]-

None

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

US Canada Mexico1 Codex2

Barley, grain 0.1 0.1

Barley, straw 0.5

Oat, forage 20.0

Oat, grain 0.1 0.1

Oat, straw 0.5

Wheat, forage 20.0

Wheat, grain 0.1 0.1

Wheat, straw 0.5

US Canada Mexico2 Codex2

US [40 CFR §180.405(a)(2)]

Livestock: Tolerances are 

established for the residues of 

chlorsulfuron (2-chloro- N- [(4-

methoxy-6-methyl-1,3,5-triazin-2-

yl)aminocarbonyl] 

benzenesulfonamide)

None

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

US Canada Mexico2 Codex3

Cattle, fat 0.3

Cattle, meat 0.3

Cattle, meat byproducts 0.3

Goat, fat 0.3

Goat, meat 0.3

Goat, meat byproducts 0.3

Grass, forage 11.0

Grass, hay 19.0

Hog, fat 0.3

Hog, meat 0.3

Hog, meat byproducts 0.3

Horse, fat 0.3

Horse, meat 0.3

Horse, meat byproducts 0.3
Page 18 of 18

Table 5. Summary of US and International Tolerances and Maximum Residue Limits for 

Chlorsulfuron 

Residue Definition:

US Canada Mexico1 Codex2

Milk 0.1

Sheep, fat 0.3

Sheep, meat 0.3

Sheep, meat byproducts 0.3

Completed: : M. Negussie; 07/16/2012

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

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

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

measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the 

CCPR and the CAC.

Table 6: HED Memoranda Relevant to Registration Review

Author Barcode Date Title

J. Abbotts D213534 04/04/1995

Results of the HED Metabolism Committee 

Meeting Held on 4/4/95: Chlorsulfuron 

Residues to be Regulated

J. Abbotts None 07/18/1995

Results of the HED Metabolism Committee 

Meeting Held on 7/18/95: Chlorsulfuron 

Residues to be Regulated in Animal 

Commodities

F. Fort D283507 07/18/2002 Chlorsulfuron Chronic Dietary Exposure 

Assessment for the TRED

F. Fort D235295 12/19/2002 Chlorsulfuron Analytical Method

F. Fort D266070 07/18/2002 Chlorsulfuron in/on Pasture Grasses. Health 

Effects Division (HED) Risk Assessment

S. Hanley D283856 07/01/2002

Chlorsulfuron Occupational and Residential 

Exposure and Risk 

Assessment/Characterization for 

Reregistration Eligibility Decision Document 

and the Proposed Use on Pasture and 

Rangeland Grasses